Virchows Archiv

The European Journal of Pathology

OFFICIAL JOURNAL OF THE EUROPEAN SOCIETY OF PATHOLOGY

Hans Kreipe, Hannover, Germany Janina Kulka, Budapest, Hungary

Editor-in-Chief
Han van Krieken, Nijmegen, The Netherlands Ryoji Kushima, Ōtsu, Japan
Daniela Massi, Florence, Italy Sunil Lakhani, Brisbane, Australia Alexander Lazar, Houston, TX, USA
Cord Langner, Graz, Austria Antonio Lopez-Beltran, Cordoba, Spain
Senior Editorial Consultant Manuel Sobrinho-Simões, Porto, Portugal Rami Mahfouz, Beirut, Lebanon
Xavier Matias-Guiu, Barcelona, Spain
Fred T. Bosman, Lausanne, Switzerland
Thomas Mentzel, Friedrichshafen, Germany
Editorial Board
Markku Miettinen, Bethesda, MD, USA
Associate Editors Abbas Agaimy, Erlangen, Germany Holger Moch, Zürich, Switzerland
Kerstin Amann, Erlangen, Germany Rodolfo Montironi, Ancona, Italy
Irene Esposito, Düsseldorf, Germany
Thomas Brenn, Edinburgh, United Kingdom George Netto, Birmingham, AL, USA
Masashi Fukayama, Tokyo, Japan
Reinhard Büttner, Bonn, Germany Carlos Ortiz-Hidalgo, Mexico City, Mexico
Sigurd F. Lax, Graz, Austria
John K.C. Chan, Hong Kong, SAR China Mauro Papotti, Turin, Italy
Leticia Quintanilla-Martinez, Tübingen, Germany
Beatrix Cochand-Priollet, Paris, France Giuseppe Pelosi, Milan, Italy
Ales Ryska, Hradec Králové, Czech Republic Aurel Perren, Bern, Switzerland
Jane Dahlstrom, Adelaide, Australia
Laura J. Tafe, Lebanon, NH, USA Guido Rindi, Rome, Italy
Ben Davidson, Oslo, Norway
Ronald de Krijger, Rotterdam, The Netherlands Christoph Röcken, Kiel, Germany
Editorial Consultants Ex Officio ESP Laurence de Leval, Lausanne, Switzerland Andreas Rosenwald, Würzburg, Germany
Michael den Bakker, Rotterdam, The Netherlands Anna Sapino, Turin, Italy
Aurelio Ariza, Barcelona, Spain
Joachim Diebold, Lucerne, Switzerland Aldo Scarpa, Verona, Italy
Marco Santucci, Florence, Italy
Peter Schirmacher, Heidelberg, Germany
Dina Tiniakos, Athens, Greece and Newcastle upon Arzu Ensari, Ankara, Turkey
Kurt Werner Schmid, Essen, Germany
Tyne, UK Fabio Facchetti, Brescia, Italy
Fernando Schmitt, Porto, Portugal
Falko Fend, Tübingen, Germany
Tomas Slavik, Pretoria, South Africa
Jean-Francois Flejou, Paris, France
Past Editors Puay-Hoon Tan, Singapore
Christopher Fletcher, Boston, MA, USA Tibor Tot, Falun, Sweden
N. Volkan Adsay, Atlanta, GA, USA Maria Pia Foschini, Bologna, Italy Toyonori Tsuzuki, Nagakute, Japan
Pierre Bedossa, Paris, France Toru Furukawa, Sendai, Japan Marc van de Vijver, Amsterdam, The Netherlands
Maria de Fátima Carneiro, Porto, Portugal Ondrej Hes, Plzen, Czech Republic Zsuzsanna Varga, Zürich, Switzerland
Manfred Dietel, Berlin, Germany Jason L. Hornick, Boston, MA, USA Giuseppe Viale, Milan, Italy
Vincenzo Eusebi, Bologna, Italy Shu Ichihara, Nagoya, Japan Akihiko Yoshida, Tokyo, Japan
Heinz Höfler, Munich, Germany Thomas Kirchner, Munich, Germany Giuseppe Zamboni, Verona, Italy
Günter Klöppel, Munich, Germany David Klimstra, New York, NY, USA Nina Zidar, Ljubljana, Slovenia

Aims and Scope marker choice. Single marker studies on limited publication, neither the authors, the editors, nor the
patient series without validated application will as a publisher can accept any legal responsibility for any
Mission statement: To advance the scientific basis of
rule not be considered. Case reports will only be errors or omissions that may have been made. The
human pathology by the publication (encouragement
considered when they provide substantial new publisher makes no warranty, express or implied,
and dissemination) of high quality research
information with an impact on understanding disease with respect to the material contained herein.
(including molecular and translational studies) and
or diagnostic practice. All articles published in this journal are protected by
thereby contribute to patient care.
Manuscripts of original studies reinforcing the copyright, which covers the exclusive rights to
evidence base of modern diagnostic pathology, using Copyright Information reproduce and distribute the article (e.g., as offprints), as
immunocytochemical, molecular and ultrastructural For Authors well as all translation rights. No material published in this
techniques, will be welcomed. In addition, papers on As soon as an article is accepted for publication, journal may be reproduced photographically or stored on
critical evaluation of diagnostic criteria but also authors will be requested to assign copyright of the microfilm, in electronic data bases, on video disks, etc.,
broadsheets and guidelines with a solid evidence base article (or to grant exclusive publication and without first obtaining written permission from the
will be considered. Consideration will also be given dissemination rights) to the publisher (respective the publisher (respective the copyright owner if other than
to reports of work in other fields relevant to the owner if other than Springer Nature). This Springer Nature). The use of general descriptive names,
understanding of human pathology as well as will ensure the widest possible protection and trade names, trademarks, etc., in this publication, even if
manuscripts on the application of new methods and dissemination of information under copyright laws. not specifically identified, does not imply that these names
techniques in pathology. Submission of purely are not protected by the relevant laws and regulations.
More information about copyright regulations for
experimental articles is discouraged but manuscripts Springer Nature has partnered with Copyright
this journal is available at www.springer.com/428
on experimental work applicable to diagnostic Clearance Center’s RightsLink service to offer a
pathology are welcomed. Biomarker studies are For Readers variety of options for reusing Springer Nature content.
welcomed but need to abide by strict rules (e.g. While the advice and information in this journal is For permission to reuse our content please locate the
REMARK) of adequate sample size and relevant believed to be true and accurate at the date of its material that
you wish to use on link.springer.com or on ISSN: 0945-6317 print version Disclaimer
springerimages.com and click on the permissions ISSN: 1432-2307 electronic version
Springer Nature publishes advertisements in this
link or go to copyright.com and enter the title of the
For information on subscription rates please contact journal in reliance upon the responsibility of the
publication that you wish to use. For assistance in
Springer Nature Customer Service Center: advertiser to comply with all legal requirements
placing a permission request, Copyright Clearance
[email protected] relating to the marketing and sale of products
Center can be contacted directly via phone: +1-855-
or services advertised. Springer Nature and the
239-3415, fax: +1-978-646-8600, or e-mail: The Americas (North, South, Central America editors are not responsible for claims made in
[email protected]. and the Caribbean) the advertisements published in the journal. The
© Springer-Verlag GmbH Germany, part of Springer Nature Journal Fulfillment, appearance of advertisements in Springer Nature
Springer Nature 2019 233 Spring Street, New York, NY, publications does not constitute endorsement,
10013-1578, USA implied or intended, of the product advertised
V.i.S.d.P F. T. Bosman
Tel. 800-SPRINGER (777-4643); 212-460-1500 or the claims made for it by the advertiser.
(outside North America)
Journal Website
Outside the Americas
Office of Publication
www.springer.com/428
Electronic edition: link.springer.com/journal/428 Springer Nature Customer Service Center GmbH Springer-Verlag GmbH, DE,
Tiergartenstr. 15, 69121 Heidelberg, Germany Heidelberger Platz 3,
Tel.: +49-6221-345-4303 14197 Berlin, Germany
Subscription Information
Virchows Archiv is published 12 times a year.
Volumes 474 (6 issues) and 475 (6 issues) will be
Advertisements
published in 2019. E-mail contact: [email protected]
31st European Congress
of Pathology
Pathology is Nice
7 – 11 September 2019
Nice Acropolis Convention Centre, France

www.esp-congress.org
Abstracts
Disclaimer
This abstract book has been produced using author-supplied texts. The publisher assumes
no responsibility for any claims, instructions or methods contained in the abstracts.

This issue was not sponsored by outside commercial interests. It was funded entirely by
the publisher.
Committees and Organisers of the ECP 2019

ESP Executive Committee and Council

Executive Committee
President Dina Tiniakos, Greece / UK
President-elect Holger Moch, Switzerland
Secretary Aurelio Ariza, Spain
Treasurer Marco Santucci, Italy
Past President Pierre Bedossa, France

Members Peter Schirmacher, Germany

Metka Volavšek, Slovenia
Tibor Tot, Sweden
Cord Langner, Austria
Xavier Matias-Guiu, Spain
Glenn McCluggage, UK
Maria Rosaria Raspollini, Italy
Anastasia Konstantinidou, Greece

Chair of the Advisory Board Fátima Carneiro, Portugal

ESP Director General Raed Al Dieri, Belgium

Scientific/Organising Committee

Members Dina Tiniakos, Greece / UK

Fátima Carneiro, Portugal
Pierre Bedossa, France
Raed Al Dieri, Belgium
Jean-François Fléjou, France
Paul Hofman, France
Jean-Christophe Sabourin, France
Working Groups of the ESP
Chair of the ESP Working Groups Pierre Bedossa, France

Autopsy Pathology
Chair C. Alfsen, Norway
Co-Chair M. Haab, Germany

Breast Pathology
Chair T. Tot, Sweden
Co-Chair G. Cserni, Hungary

Cytopathology
Chair P. Vielh, Luxembourg
Co-Chair G. Troncone, Italy
Dermatopathology
Chair E. Calonje, UK
Co-Chair B. Luzar, Slovenia

Digestive Diseases Pathology

Chair J.-F. Fléjou, France
Co-Chair C. Sempoux, Switzerland

Electron Microscopy
Chair G. Cenacchi, Italy
Co-Chair D. Naranjo-Hans, Spain

Endocrine Pathology
Chair J.-Y. Scoazec, France
Co-Chair C. Eloy, Portugal

Gynaecological Pathology
Chair S. Stolnicu, Romania
Co-Chair A. Vidal Bel, Spain

Head and Neck Pathology

Chair T. R. Helliwell, UK
Co-Chair N. Zidar, Slovenia

History of Pathology
Chair G. Nesi, Italy

Infectious Diseases Pathology

Chair G. Gorkiewicz, Austria
Co-Chair N. Rakislova, Spain

IT (Computational)
Chair G. Kayser, Germany

Molecular Pathology
Chair G. Hoefler, Austria
Co-Chair G. Stanta, Italy

Nephropathology
Chair K. Amann, Germany
Co-Chair H. Hopfer, Switzerland

Paediatric and Perinatal Pathology

Chair I. Colmenero, Spain
Co-Chair A. Coulomb, France

Pathology In Favour of Developing Countries

Chair S. Guzzetti, Italy
Co-Chair G. de Falco, Italy
Pulmonary Pathology
Chair F. Calabrese, Italy
Co-Chair I. Kern, Slovenia

Soft Tissue and Bone Pathology

Chair F. Le Loarer, France
Co-Chair D. Baumhoer, Switzerland

Thymic and Mediastinal Pathology

Chair P. Ströbel, Germany
Co-Chair M. Szolkowska, Poland

Uropathology
Chair A. Lopez-Beltran, Spain
Co-Chair M. Colecchia, Italy

AFFILIATED SOCIETIES

Cardiovascular Pathology
President J. Lucena, Spain
Secretary G. D’Amati, Italy

Haematopathology
President D. de Jong, The Netherlands
Secretary B. Sander, Sweden

Neuropathology (Euro – CNS)

President P. Ince, UK

Ophthalmic Pathology
President R. M. Verdijk, The Netherlands

Paediatric Pathology
President G. Vujanic, Qatar
Secretary S. Holden, UK
Oral Free Paper Sessions

OFP-01 Oral Free Paper Session Joint Session: Uropathology / Nephropathology

OFP-02 Oral Free Paper Session Digestive Diseases Pathology - GI
OFP-03 Oral Free Paper Session Cytopathology
OFP-04 Oral Free Paper Session Breast Pathology
OFP-05 Oral Free Paper Session Digestive Diseases Pathology - Liver / Pancreas
OFP-06 Oral Free Paper Session Joint Session: Endocrine Pathology / Head and Neck Pathology
OFP-07 Oral Free Paper Session Dermatopathology
OFP-08 Oral Free Paper Session Joint Session: Neuropathology / Ophthalmic Pathology
OFP-09 Oral Free Paper Session Joint Session: Autopsy Pathology / Cardiovascular Pathology / History
of Pathology / IT in Pathology / Pathology in Favour of Developing Countries / Other Topics
OFP-10 Oral Free Paper Session Joint Session: Pulmonary Pathology / Thymic and Mediastinal
Pathology
OFP-11 Oral Free Paper Session Joint Session: Soft Tissue and Bone Pathology / Infectious Diseases
Pathology
OFP-12 Oral Free Paper Session Paediatric and Perinatal Pathology
OFP-13 Oral Free Paper Session Joint Session: Molecular Pathology / Haematopathology
OFP-14 Oral Free Paper Session Gynaecological Pathology

Oral Free Paper Sessions One-Day CPS and Two-Day MDS

CP-03 One-Day Computational Pathology Symposium – Selected Abstracts

MD-01 Two Day Molecular Diagnostics Symposium – Selected Abstracts
MD-05 Two Day Molecular Diagnostics Symposium – Selected Abstracts

Poster Sessions

PS-01 Poster Session Breast Pathology

PS-02 Poster Session Gynaecological Pathology
PS-03 Poster Session Head and Neck Pathology
PS-04 Poster Session Molecular Pathology
PS-05 Poster Session Dermatopathology
PS-06 Poster Session Electron Microscopy
PS-07 Poster Session Haematopathology
PS-08 Poster Session Infectious Diseases Pathology
PS-09 Poster Session IT in Pathology
PS-10 Poster Session Nephropathology
PS-11 Poster Session Neuropathology
PS-12 Poster Session Other Topics
PS-13 Poster Session Pulmonary Pathology
PS-14 Poster Session Cytopathology
PS-15 Poster Session Ophthalmic Pathology
PS-16 Poster Session Paediatric and Perinatal Pathology
PS-17 Poster Session Uropathology
PS-18 Poster Session Autopsy Pathology
PS-19 Poster Session Cardiovascular Pathology
PS-20 Poster Session Digestive Diseases Pathology - GI
PS-21 Poster Session Digestive Diseases Pathology - Liver / Pancreas
PS-22 Poster Session Endocrine Pathology
PS-23 Poster Session History of Pathology
PS-24 Poster Session Pathology in Favour of Developing Countries
PS-25 Poster Session Soft Tissue and Bone Pathology

Poster Sessions One-Day CPS and Two-Day MDS

PS-CP-01 Poster Session One-Day Computational Pathology Symposium

PS-MD-01 Poster Session Two Day Molecular Diagnostics Symposium

E-Posters

E-PS-01 E-Posters Autopsy Pathology

E-PS-02 E-Posters Breast Pathology
E-PS-03 E-Posters Cardiovascular Pathology
E-PS-04 E-Posters Cytopathology
E-PS-05 E-Posters Dermatopathology
E-PS-06 E-Posters Digestive Diseases Pathology – GI
E-PS-07 E-Posters Digestive Diseases Pathology – Liver / Pancreas
E-PS-08 E-Posters Endocrine Pathology
E-PS-09 E-Posters Gynaecological Pathology
E-PS-10 E-Posters Haematopathology
E-PS-11 E-Posters Head and Neck Pathology
E-PS-12 E-Posters History of Pathology
E-PS-13 E-Posters Infectious Diseases Pathology
E-PS-14 E-Posters IT in Pathology
E-PS-15 E-Posters Molecular Pathology
E-PS-16 E-Posters Nephropathology
E-PS-17 E-Posters Neuropathology
E-PS-18 E-Posters Ophthalmic Pathology
E-PS-19 E-Posters Other Topics
E-PS-20 E-Posters Paediatric and Perinatal Pathology
E-PS-21 E-Posters Pathology in Favour of Developing Countries
E-PS-22 E-Posters Pulmonary Pathology
E-PS-23 E-Posters Soft Tissue and Bone Pathology
E-PS-24 E-Posters Thymic and Mediastinal Pathology
E-PS-25 E-Posters Uropathology

E-Posters One-Day CPS

E-PS-CP-01 E-Posters One-Day Computational Pathology Symposium

 springer.com

Encyclopedia of Pathology
J. H. J. M. van Krieken (Series Ed.)

The scope of this 15–20-volume set addresses the entire field of pathology, ranging from general pathological
terms to specific diseases to diagnostic methods. Published as print edition and online version (eReference)
in the Springer Reference Program each topical volume sticks out by clearly and homogenously structured
entries. A team of international experts guarantee that the essays and definitions are scientifically sound.
The A-Z format of each topical volume allow readers to quickly and easily find the information they need.
The major advantage of the encyclopedia is the way it makes relevant information available not only to
pathologists, but also to all clinicians and researchers of the neighboring disciplines working together with
pathologists who occasionally might wish to look up terms online.

Upcoming Volumes:
• M. Volavsek (Ed.) • D. Massi (Ed.)
Head and Neck Pathology Dermatopathology

• P. Slootweg (Ed.) • P. Hofman (Ed.)

Dental and Oral Pathology Infectious Disease and Parasites

Easy Ways to Order for the Americas: Write: Springer Order Department, 233 Spring Street, New York, NY 10013-1578
Call: (toll free) 1-800-SPRINGER | Fax: +1(212)460-1700 | Email: [email protected] or for outside the Americas: Write:
Springer Customer Service Center GmbH, Haberstrasse 7, 69126 Heidelberg, Germany | Call: +49 (0) 6221-345-4301 | Fax: +49 (0) 6221-345-4229
Email: [email protected] | Prices are subject to change without notice. All prices are net prices.

springer.com/shop
 springer.com

Keeling‘s Fetal and

Neonatal Pathology
T. Yee Khong, Roger D. G. Malcomson (Eds.)

This fifth edition of a successful book provides an overview of fetal and perinatal pathology, concentrating
on common problems, especially where the anatomical pathology findings guide the direction of further
investigations.

A new feature of this edition is an emphasis on the molecular aspects of pathology in the perinatal setting.
There are four new chapters, including one on the genetic and epigenetic basis of development and disease,
and over 300 new illustrations. The format of the book remains the same as previous editions with the first half
covering general areas in perinatal pathology. The second half is based on organ systems and covers specific
pathological entities, now including discussion of the relevant molecular pathology. There is extensive cross-
referencing between chapters.

5th ed. 2015. XVII, 882 p. 717 illus., 611 illus. in color. Hardcover
ISBN 978-3-319-19206-2
€ 259,00 | £233.50

Easy Ways to Order for the Americas: Write: Springer Order Department, 233 Spring Street, New York, NY 10013-1578
Call: (toll free) 1-800-SPRINGER | Fax: +1(212)460-1700 | Email: [email protected] or for outside the Americas: Write:
Springer Customer Service Center GmbH, Haberstrasse 7, 69126 Heidelberg, Germany | Call: +49 (0) 6221-345-4301 | Fax: +49 (0) 6221-345-4229
Email: [email protected] | Prices are subject to change without notice. All prices are net prices.

springer.com/shop
Blank
Virchows Archiv
https://doi.org/10.1007/s00428-019-02631-8

ABSTRACTS

Abstracts
31st European Congress of Pathology

Oral Free Paper Sessions Berlin, Germany, 3 Institute of Pathology, RWTH Aachen University,
Germany, 4 Hôpital Tenon, HUEP, Sorbonne University, Paris, France, 5
Institute of Pathology, University of Bern, Switzerland, 6 Department of
Urology and Paediatric Urology, University Hospital Erlangen, Friedrich-
Sunday, 8 September 2019, 08:30 - 12:00, Galliéni 5 Alexander Universität Erlangen-Nuernberg, Germany, 7 Department of
OFP-01 | Joint Session: Uropathology / Nephropathology Pathology, Hôpital Foch, Universitè Versailles-Saint-Quentin-en-Yvelines,
Universitè Paris-Saclay, Suresnes, Francle; Institut Curie, CNRS, UMR144,
Paris, France, 8 Institute of Pathology, University Hospital Bonn, Germany
OFP-01-001
The influence of the presence of intraductal carcinoma of the prostate Background & Objectives: Nested variant of urothelial carcinoma
on the grade group system's prognostic performance (NVUC) is rare and only few small series exist. Molecular characteristics
T. Tsuzuki1, M. Kato2 and the classifying marker profile as well as therapeutic targets of this
1
Department of Surgical Pathology, Aichi Medical University Hospital, specific variant are mostly unknown. Aim of this study was to character-
Japan, 2 Department of Urology, Nagoya University Graduate School of ise NVUC on the molecular level in one of the largest cohorts to date. In
Medicine, Japan addition, we applied an immunohistochemical marker panel in order to
define the molecular subtype of this variant.
Background & Objectives: Although the presence of intraductal carci- Methods: 60 NVUC cases were collected from different departments.
noma of the prostate (IDC-P) influences biochemical failure in radical TERT promoter mutation analysis was carried out in all samples using
prostatectomy patients, no data are available regarding the impact of its SNaPshot analysis. Target sequencing of 48 cancer related genes by Next
integration into the classification Grade Group system. Thus, the aim of Generation Sequencing (NGS) analysis was performed in a subset of 26
this study was to enhance the utility of the Grade Group (GG) system by cases. Immunohistochemical markers CD44, CK5, CK14, EGFR, p63,
integrating the presence of IDC-P. FOXA1, GATA3, CD24 und CK20 were used to elucidate the molecular
Methods: This study was a retrospective evaluation of 1019 patients with subtype.
prostate cancer who underwent radical prostatectomy between 2005 and Results: A total of 62.5% of NVUC cases harbored a mutation of the TERT
2013 without neoadjuvant or adjuvant therapy. Data on age, prostate- promoter. Additionally, TP53 and JAK3 were among the most frequently
specific antigen (PSA) level at diagnosis, pathological T stage (pT), the mutated genes identified by NGS analysis. Subtyping revealed that all
presence of Gleason pattern 5 (GP5), the presence of IDC-P, and surgical NVUC express luminal markers such as CD24, FOXA1, GATA3 and CK20.
margin status were analysed to predict PSA recurrence after prostatectomy. Conclusion: Summarized, NVUC belong to the luminal molecular sub-
Results: IDC-P was detected in 157 patients (15.4%). GGs were as fol- type. Moreover, a subset of NVUC seems to be characterised by muta-
lows: GG1 without IDC-P, n=163; GG2 without IDC-P, n=470; GG3 tions of the Wnt- and inflammatory pathway, including JAK3 mutations,
without IDC-P, n=160; GG4 without IDC-P, n=27; GG5 without IDC-P, indicating a different biological background compared to conventional
n=42; any GG with IDC-P, [n=157; GG 2 (n=29); GG3 (n=60); GG4 urothelial bladder cancer.
(n=13); GG5 (n=55)]. Any GG with IDC-P showed a significantly worse
prognosis than any other GG without IDC-P (p< 0.0001). In a multivar-
iate analysis, integration of the IDC-P into the GGs was significant prog- OFP-01-003
nostic predictors (P < 0.0001). A new auto-annotation method and machine learning strategy for
Conclusion: Integrating the presence of IDC-P into the GG system will detection and annotation of cancer areas in prostate biopsies
result in more accurate predictions of patient outcome. L. Björk1,2, J. Gustafsson3, F. Hikmet Noraddin3 , K. Eurèn2, C.
Lindskog3
1
Karolinska Institutet, Sweden, 2 Contextvision, Sweden, 3 Uppsala
OFP-01-002 Universitet, Sweden
Distinct genetic alterations and luminal molecular subtype in nested
variant of urothelial carcinoma Background & Objectives: Prostate cancer is one of the most diagnosed
V. Weyerer1, R. Weisser1, E.A. Moskalev1, F. Haller1, R. Stoehr1, M. cancer forms and a leading cause of cancer-related death in males. The
Eckstein1, U. Zinnall2, N.T. Gaisa3, E. Compèrat4, A. Perren5, B. examination and Gleason scoring of prostate biopsies is however a major
Keck6, Y. Allory7, G. Kristiansen8, B. Wullich6, A. Agaimy1, A. bottleneck in the pathology workflow, and studies have shown that the
Hartmann1, S. Bertz1 inter-observer variability in scoring is high. For increasing accuracy and
1
Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander speeding up the decision process, there is a high demand for implemen-
University Erlangen, Germany, 2 Institute of Medical Systems Biology, Max tation of an image analysis tool to support pathologists. The aim of the
Delbrück Center for Molecular Medicine in the Helmholtz Association, present investigation was to develop a strategy for un-biased, specific
 Virchows Arch

detection of cancer areas in clinical prostate biopsy images, and use the Conclusion: It appears that the immunohistochemically negative tu-
outlined areas as training material for machine learning algorithms. mours are a heterogeneous group and a part of them respond to an
Methods: Prostate sections were stained towards Cytokeratin 5/6, p63, immununchekpoint blockade. The detection of PD-L1 RNA may be an
Cytokeratin 8/18 and AMACR, and digitalized using immunofluorescence extended diagnostic step that improves the prediction of therapy
slide scanning. The same slides we stained with hematoxylin and eosin Response.
(HE) and scanned in brightfield. The immunofluorescence stainings gener-
ated high-resolution multiplex images marking specific structures in the
prostate biopsies, accurately outlining the cancer containing areas. The OFP-01-005
multiplex images where then overlaid with corresponding HE images, Genomic landscape of young-onset bladder cancer and it's prognos-
and the antibody stained structures thus served as masks to accurately mark tic implication on adult bladder cancer
cancer areas in the HE images. The HE images along with marked cancer Y.M. Cho1, S. Im2, C.O. Sung1, K.S. Kim1, N.H. Cho3, Y.M. Kim4, G.Y.
areas were used for training models to distinguish benign prostate glands Kwon5, K.C. Moon2, S. Choi6, J.S. Lim6, Y.J. Choi7, S.J. Jung8, S.D.
from cancerous glands using machine learning algorithms. Lim9, S.H. Paick9, O. Lee10, H.W. Kang10, S.H. Rha11, H.S. Hwang1, J.
Results: The multiplex images with added annotation specifically Park12, S.Y. Yoon12, J. Kim2
1
outlining the parenchyma using the epithelial biomarker generated a Asan Medical Center, Republic of Korea, 2 Seoul National University,
high-resolution annotation mask suitable for machine learning. Republic of Korea, 3 Yonsei University College of Medicine, Republic of
Preliminary data on the first 63 biopsies show that the model can accu- Korea, 4 Ulsan University Hospital, Republic of Korea, 5 Samsung Medical
rately outline cancerous glands with high precision. The results were Center, Republic of Korea, 6 Chungnam National University College of
confirmed in an independent set of HE images manually annotated by Medicine, Republic of Korea, 7 The Catholic University of Korea,
three different pathologists. Republic of Korea, 8 Inje University Busan Paik Hospital, Republic of
Conclusion: In summary, we have developed a robust and powerful Korea, 9 Konkuk University, Republic of Korea, 10 Chungbuk National
method for specific and objective visualisation of cancer areas in prostate University Hospital, Republic of Korea, 11 Dong-A University, Republic of
biopsy images, and used these images for machine-learning in order to Korea, 12 Asan Institute of Life Science, Republic of Korea
develop a highly accurate decision support tool for pathologists.
Background & Objectives: Bladder cancer is common in elderly men,
Cecilia Lindskog is funded by Verification for collaboration, Uppsala and it is a highly mutated tumour with frequent TP53 and FGFR3 muta-
University for development of an AI method to improve diagnosing pros- tion. Young-onset bladder cancer (YBC) is extremely rare; therefore, its
tate cancer in collaboration with ContextVision. genomic characteristics are unknown and appropriate management strat-
egy is yet to be defined. This study is aimed to delineate the genomic
landscape of YBC and to compare it to those of adult bladder cancer
OFP-01-004 (ABC).
Detection of PD-L1 RNA expression in immunohistochemically neg- Methods: Twenty nine cases of biopsy-proven YBCs diagnosed at 20
ative patients. Are the negatives a heterogenous group? years or younger were collected through a nation-wide search of the
U. Sommer1, M. Großer1, D. Aust1,2,3, K. Jöhrens1, P. Hönscheid1,3, G. archived files from the Korean Genitourinary Study Group of the
Baretton1,2,3 Korean Society of Pathologists. Whole exome sequencing and RNA se-
1
Institut für Pathologie, University Hospital Carl Gustav Carus, Medical quencing were performed on 21 and 11 cases, respectively, and the results
Faculty, Technische Universität Dresden, Germany, 2 Tumour and were compared with those of adult bladder cancer (ABC) retrieved from
Normal Tissue Bank of the University Cancer Center (UCC), public database.
University Hospital Carl Gustav Carus, Medical Faculty, Technische Results: Driver mutations were found in all cases. Common mutations
Universität Dresden, Germany, 3 Core Unit for Molecular Tumour included HRAS mutations (10 cases) and FGFR3 gene fusions (7 cases).
Diagnostics (CMTD), National Center for Tumour Diseases (NCT) Others were KRAS mutations (2 cases), arm-level deletion of chromo-
Dresden, Germany somes 4p and 10q (1 case), and ERCC2 mutation (1 case). TP53 and
FGFR3 point mutations were not found. The gene expression profiles
Background & Objectives: Immune-checkpoint inhibition is an already of YBC corresponded to those of the good prognostic group of ABC.
well established therapy for advanced urothelial carcinoma (UC). None of YBC cases and ABCs with YBC-like mutations had progressed
Identification of patients who are likely to respond to PD-1 or PD-L1 to muscle-invasive tumour.
blockade is of paramount importance for clinical decision making. In Conclusion: YBC had distinct driver genetic alterations such as HRAS
different clinical trials a correlation between immunohistochemical PD- mutation and FGFR3 gene fusion and showed good prognosis. YBCs and
L1 expression and response to checkpoint inhibition has been shown. ABCs with YBC-like mutations may be managed with less aggressive
Interestingly, there are patients who respond to immunecheckpoint ther- surveillance.
apy despite lack of PD-L1 expression. These observations and experi-
ences suggest that there might be differences in biology of the tumours, National Research Foundation of Korea (2015R1A2A2A01006958) and
which are only partially revealed by the various available diagnostic the Korea Health Technology R&D Project (HI13C2148)
antibodies/kits. We investigated PD-L1 RNA expression in metastasized
UC in order to be able to detect potential differences in the tumours one
step ahead of the protein level. OFP-01-006
Methods: 21 formalin-fixed, paraffin-embedded (FFPE) resection spec- Intra and interpatient genetic features of intraductal carcinoma of
imens from patients with metastasized UC were immunostained for PD- the prostate
L1 ( E1L3N-antibody, Cell Signaling). Consecutively RNA ISH was M. Downes1, A. Hodgson1, S. Chen2, H. He2, S. Liu3, D. Vesprini3
1
performed to detect PD-L1 RNA ( ViewRNA ISH Tissue 2-Plex Assay, Sunnybrook Health Sciences Centre, Canada, 2 Princess Margaret
Thermo Fisher) and the PD-L1 target specific probe set (VA1-14391-01). Cancer Centre, Canada, 3 Radiation oncology, Sunnybrook Health
Results: While protein and RNA expression on tumour and immune cells Sciences Centre, Canada
show comparable results in the IHC positive patient group, we found PD-L1
RNA expression on tumour cells in the IHC negative group. IHC negative Background & Objectives: Intraductal carcinoma of prostate (IDC) is a
patients did not show PD-L1 RNA expression on their immune cells. morphologic pattern that is associated with adverse patient outcome. The
Virchows Arch

molecular underpinnings of IDC are not yet fully elucidated, particularly OFP-01-008
in comparison with background prostate. TFEB-amplified renal cell carcinoma: a comprehensive study of 7
Methods: A pilot analysis was conducted using 10 randomly selected novel cases
patients who underwent radical prostatectomy and who had IDC. IDC S. Kammerer-Jacquet1, C. Gandon1, F. Dugay2, M. Beaumont2, K.
was confirmed using immunohistochemistry. Benign prostatic tissue, Bensalah3, M. Belaud-Rotureau2, N. Rioux-Leclercq1
1
conventional acinar adenocarcinoma and IDC were sampled from each Department of Pathology, University Hospital, Rennes, France,
2
case using needle punches. DNA extraction was performed with the Department of Cytogenetics, University Hospital, Rennes, France,
3
RecoverAll total nucleic acid isolation kit and samples (n=30) were run Department of Urology, University Hospital, Rennes, France
on a Thermo Fisher Ion Torrent S5XL platform using the Oncomine
Comprehensive Assay v3. Copy number variants (CNVs) and single Background & Objectives: First described in 2014, renal cell carcinoma
nucleotide variants (SNVs) within and between patient samples were (RCC) with TFEB amplification (6p21) is a rare entity whose diagnosis is
evaluated. Bioinformatic analyses was performed using the computing challenging. The prognosis and therapeutic implications remain unclear.
environment R. Methods: We report herein the clinical, histological, immunohistochem-
Results: 2/10 patients had BRCA2 mutations in benign, acinar car- ical and genetic features of 7 novel cases. The pathological and immuno-
cinoma and IDC, suggestive of an underlying germline defect. No histochemical features were centrally reviewed by expert uropathologists.
significant differences for SNVs were detected within or between Fluorescence in situ hybridization (FISH) confirmed the diagnosis and
patients using this panel. CNV analysis demonstrated a trend to- comparative genomic hybridization (CGH) was performed to determine
wards gain of the proto-oncogene MYC in IDC and also EZH2 quantitative and structural genetic alterations.
compared with matching benign and acinar adenocarcinoma with Results: TFEB-amplified RCC were locally advanced with initial lymph
reduced gain of p53 and loss of PTEN. node involvement in one case and liver metastasis in another case. They
Conclusion: BRCA2 mutations (perhaps germline) exist in our cohort of were high grade eosinophilic tumours with papillary or pseudopapillary
IDC cases. This finding could have implications for genetic testing and ther- architecture and frequent melanocytic marker expression. The FISH anal-
apeutic options (ex. PARP inhibitors). In addition, gains in MYC and EZH2 ysis demonstrated high-level TFEB amplification with two TFEB concur-
with reduced gain in p53 and loss of PTEN were noted in the IDC compo- rent translocations. The CGH analysis identified complex alterations with
nent, providing some insight into the molecular evolution of this entity. frequent losses of 1p, 2q, 3p, 18q and gain of 8q. VEGFA was co-
amplified in all cases. In the follow-up, one patient had a lymph node
recurrence and another one developed bone metastases.
Conclusion: TFEB-amplified RCC is a rare entity with variable morphol-
OFP-01-007 ogy whose diagnosis is confirmed by FISH analysis. The complex alter-
Papillary renal cell carcinoma with prominent spindle cell stroma - ations identified by CGH analysis is concordant with an aggressive clin-
tumour mimicking MESTK , clinicopathologic analysis of 5 cases ical behaviour. The co-amplification of VEGFA could suggest a potential
J. Rogala1, K. Pivovarcikova2, M. Ulamec3,4, R. Alaghehbandan5, F. benefit from anti-angiogenic therapy.
Kojima6
1
Department of Pathology, Regional Specialist Hospital, Wrocław,
Poland, 2 Department of Pathology, Charles University, Medical
Faculty and Charles University Hospital Plzen, Czech Republic, OFP-01-009
3
Clinical Department of Pathology and Cytology "Ljudevit Jurak", Improvement of vascular invasion scoring in stage I testicular non-
University Hospital Centre Sestre Milosrdnice, Zagreb, Croatia, seminomas to predict relapse during surveillance after orchiectomy
4
Department of Pathology, School of Medicine, University of J. Lobo1, H. Stoop2, A. JM Gillis3, K. van Kerckhoven4, L. Budel5, M.
Zagreb, Zagreb, Croatia, 5 Department of Pathology, Faculty of den Bakker5, L. HJ Looijenga6, J.W. Oosterhuis2
1
Medicine, University of British Columbia, Royal Columbian IPO Porto, Portugal, 2 Erasmus MC Rotterdam, The Netherlands,
3
Hospital, Vancouver, Canada, 6 Shin-ichi Murata, Department of PMC Utrecht, The Netherlands, 4 Cabinet Tolbiac, France, 5 Maasstad
Human Pathology, Wakayama Medical University, Wakayama, Japan Ziekenhuis, Rotterdam, The Netherlands, 6 PMC Utrecht & Erasmus MC
Rotterdam, The Netherlands
Background & Objectives: Papillary Renal Cell Carcinomas (PRCCs)
are traditionally divided on type 1 and type 2. Recent studies confirm Background & Objectives: Vascular invasion (VI) has been identified as
relative uniformity within type 1 PRCCs in contrast to type 2, showing an informative risk factor for relapse in stage I testicular non-seminomas
broad spectrum of morphologic, immunohistochemical and molecular (NS), used to tailor treatment options. We investigated inter-observer
featutes. We selected a series of unusual PRCCs with spindle cell stroma agreement in VI reporting and studied the potential additional value of
resembling mixed epithelial and stromal tumour (MESTK) of kidney to immunohistochemistry for vascular markers for predicting relapse.
assess clinicopathological features. Methods: Patients (n=52) with stage I testicular NS undergoing surveil-
Methods: Five cases of PRCCs with prominent spindle cell stroma lance (1993-2006) were included (median follow-up of 66 months). Two
(PRCCSCS) were analysed using morphologic , immunohistochemical FFPE blocks with >1cm2 tissue and tumour/normal parenchyma interface
and array CGH methods. were stained with H&E and CD31, FVIII and D2-40. Slides were
Results: Tumours revealed papillary to tubulopapillary architecture. assessed by five independent observers (two general and three germ cell
Epithelial cells were mainly eosinophilic, nuclear grade 2 and 3 (WHO/ tumour (GCT)-dedicated pathologists) and agreement was assessed using
ISUP). Spindle cell stroma showed no malignant or heterogenous ele- Cohen’s Kappa statistic. Sensitivity, specificity and accuracy of VI scor-
ments. Mitotic index was low in both compartments. ing in predicting relapse were calculated.
Epithelial cells were positive for CK7, AMACR, vimentin and FH. Results: Agreement between general pathologists was inferior when
Stroma was positive for vimentin, actin and focally for CD34. Estrogen compared to concordance among GCT-dedicated pathologists (k=0.25
and progesterone were negative in both elements. vs. k=0.49-0.54, respectively), as was performance in predicting disease
Copy numer variation pattern was variable (multiple gains and losses). relapse (particularly specificity of 43% vs. 86%, respectively). Most dis-
Conclusion: PRCCSCS is distinct variant of PRCC, which cannot be agreements corresponded to over-scoring VI by general pathologists.
futher subclassified according to WHO 2016. MESTK, sacromatoid RCC Immunohistochemistry increased overall sensitivity (71%) but decreased
and RCC with leiomyomatous stroma are main differential diagnoses. specificity (71%). All patients (n=8) with both blood and lymphatic VI
 Virchows Arch

developed relapse. In multivariable analysis only VI had an independent RCCs(54%). All but one t(6;11)RCC expressed melanogenesis
impact in predicting relapse. markers. Among Xp11 RCCs, nine(36%)showed a patchy staining
Conclusion: Assessment of VI should be performed by a GCT-dedicated for HMB45; whereas Melan-A was observed in 3 multicystic tu-
pathologist. Immunohistochemistry for vascular markers improves sensi- mours. Proximal tubular markers, CD10 and CD13, were positive
tivity of detecting VI and allows detection of high-risk patients with both in 27 of 30(90%) and 14 of 28(50%)tumours. Distal tubular markers,
blood and lymphatic VI, potentially of interest for tailored chemotherapy. parvalbumin and GATA3, stained 11 of 26(42%) and 0 of 34 cases.
Patchy staining for CAIX was found in 9 of 29(31%); AMACR and
PhD Grant by FCT (grant number SFRH/BD/132751/2017). Project S100A1 were diffusely positive in the majority of tumours. Focal
Grant by FCT (grant number POCI-01-0145-FEDER-29043). immunolabelling for CK7 and CK8-18 was observed in 4 of
30(13%) and in 20 of 31(64%)tumours. None of them expressed
CD68(PG-M1). SDHB and FH were retained in all cases.
OFP-01-010 Conclusion: An immunohistochemical panel including cathepsinK,
Correlation of mismatch repair deficiency with expression of PD-L1 melanogenesis markers, CAIX, CD68(PG-M1), CK7 and GATA3 is
and CD8 in high grade urothelial carcinoma of bladder useful in the differential diagnosis. The findings also suggests the
M. Downes1, A. Hodgson1, B. Xu2 differentiation toward to proximal tubules in MiT family transloca-
1
Sunnybrook Health Sciences Centre, Canada, 2 Memorial Sloan Kettering tion RCC.
Cancer Center, USA

Background & Objectives: Mismatch repair (MMR) deficiency has OFP-01-012

been associated with therapeutic susceptibility to inhibitors of the PD-1/ Immune cell infiltration in paediatric renal allografts: mononuclear
PD-L1 axis. In this study, we sought to correlate loss of MMR protein phagocytes correlate with rejection, re-transplantation and fibrosis
expression with CD8 and PD-L1 expression in a cohort of high grade in a retrospective study
urothelial carcinoma (HGUC). J. Schmitz1, S. Senger1, A. Khalifa1, A. Tramm2, N. Richter3, T.
Methods: Triplicate tissue microarrays (TMAs) were constructed Ahlenstiel-Grunow2, L. Pape1, J.H. Bräsen1
1
with tumour tissue from 207 HGUCs. TMA sections were stained Institute of Pathology, Hannover Medical School, Germany, 2 Paediatric
with CD8, MLH1, PMS2, MSH2, MSH6 and PD-L1 (SP263). CD8 Nephrology, Hannover Medical School, Germany, 3 Clinic for General,
was scored in a hotspot fashion (1 representative 40x field/core Abdominal and Transplant Surgery, Hannover Medical School, Germany
scored; averaged across 3 cores). MMR expression was assessed in
tumour nuclei and membranous PD-L1 expression was evaluated in Background & Objectives: Standardised markers of immune cell infil-
immune cells and tumour cells. Cases with loss of MMR expression tration in renal transplantation may improve diagnostics. To date, no
on TMA sections were evaluated with MMR and PD-L1 stains using larger study investigating the role of immune cells in renal paediatric
whole tissue sections. allografts exists and their impact on long-term outcome is poorly
Results: 207 cases were evaluable. Loss of MMR expression was understood.
confirmed in 4 cases (2%) on whole tumour sections; 3 cases showed Methods: All graft samples (n=202) from 59 paediatric patients (63 %
MLH1/PMS2 loss while one case showed MSH2/MSH6 loss. CD8 male, mean age 10 years) transplanted 2000-2017 at our center were re-
expression was higher in MMR-deficient cases compared to other evaluated according to recent Banff criteria and stained for macrophages,
cases in the cohort (mean 108.2 vs. 34.7, p=0.007). PD-L1 expres- dendritic cells, B cells and T cells (CD68, CD206, CD163L1, CD209,
sion was positive in 3 MMR-deficient cases but the MSH2/MSH6 CD20, CD3). Quantification of immune cells was performed in whole
loss case was PD-L1 negative. PD-L1 expression was seen in 20% slide images (WSI) using image analysis software (QuPath). Results were
(41/203) of cases with retained MMR proteins. obtained separately for cortex, medulla and extrarenal tissue and
Conclusion: MMR deficiency is rare in HGUC however, these tumours displayed as percentages (%) of positively stained area.
show a higher rate of PD-L1 positivity and increased CD8+ infiltrate Results: In TCMR (T cell mediated) and ABMR (antibody mediated
compared to MMR intact HGUCs. The very low rate of MMR deficiency rejection) cortical macrophages were more frequent than in samples with-
does not warrant routine use of these stains in HGUC. out rejection (p<0.05; Kruskal-Wallis test); B cells were most abundant in
TCMR (p<0.001). In re-transplanted (2nd to 4th) organs a higher density
of macrophages than in first allografts was observed (p<0.05). Protocol
OFP-01-011 biopsies had lower macrophage numbers than indication biopsies
MiT family translocation renal cell carcinoma: an immunohisto- (p<0.01; Mann-Whitney U test). Infiltration of dendritic cells revealed
chemical panel for the differential diagnosis higher densities in i-IFTA1, i-IFTA2 and i-IFTA3 compared to i-IFTA0
A. Caliò1, M. Brunelli1, D. Segala2, G. Martignoni1 (p<0.05) within renal cortex. Macrophage numbers correlated with fibro-
1
University of Verona, Italy, 2 Ospedale Pederzoli, Peschiera del Garda, Italy sis (% IFTA; Spearman’s r>0.4, p<0.001).
Conclusion: Infiltrating immune cells, particularly mononuclear phago-
Background & Objectives: Due to the wide morphological spectrum of cytes, are highly abundant in paediatric renal transplants in rejection, re-
MiT family translocation renal cell carcinoma(RCC) the differential di- transplantation and fibrosis and might influence long-term graft function.
agnosis is challenging and includes clear cell RCC, papillary RCC, clear Actually, our morphologic findings are correlated with clinical data and
cell papillary RCC and epithelioid PEComa. outcome.
Methods: We collected 34 MiT family translocation RCCs (26 Xp11 and
8 t(6;11)RCCs) and performed an immunohistochemical panel including
PAX8, cathepsinK, HMB45, Melan-A, CD10, CD13, CK7, CK8-18, OFP-01-013
carbonic anhydraseIX(CAIX), α-methylacyl-CoA racemase(AMACR), Genotype-phenotype correlation for novel COL4A4 splice site muta-
S100A1, parvalbumin, GATA3, CD68(PG-M1), SDHB and fumarate tion causing autosomal Alport spectrum disorders
hydratase(FH). FISH analysis for TFE3 and TFEB rearrangement was P. Senjug1, T. Nikuseva Martic2, M. Senjug Perica3, M. Oroz4, M.
carried out. Horacek5, M. Cuk6, S. Abdovic6, J. Vlasic - Matas7, K. Galesic8, D.
Results: TFE3 and TFEB translocation was observed in 26 and 8 Galesic Ljubanovic1,5
1
tumours respectively. PAX8 was positive in almost all cases(90%). Unit of Nephropathology and Electron Microscopy, Department of
CathepsinK was observed in all t(6;11)RCCs and 14 of 26 Xp11 Pathology and Cytology, Dubrava University Hospital, Zagreb, Croatia,
Virchows Arch

2
Department of Biology and Medical Genetics, School of Medicine, Results: A cut-off >5.5 CD68 positive cells in the most affected glomer-
University of Zagreb, Croatia, 3 Division of Rheumatology, Srebrnjak ulus (CD68max) resulted in an area under the curve (AUC) of 0.966.
Children's Hospital, Zagreb, Croatia, 4 University of Zagreb, School of CD68max correlated with the percentage of glomeruli with CD68 counts
Medicine, Croatia, 5 Institute of Pathology, School of Medicine, above the cut-off (ρ = 0.875). Three risk groups (baseline, low, high) with
University of Zagreb, Croatia, 6 Department of Paediatrics, Children's prognostic impact on graft survival were established using ROC compar-
Hospital Zagreb, Croatia, 7 Polyclinic Dr. Vlasic, Split, Croatia, ing cases with glomerular Banff scores 0 vs. 1 (AUC = 0.891, cut-off >
8
Department of Nephrology and Dialysis, Dubrava University 3.9 % of glomeruli) and 1 vs. 2-3 (AUC = 0.867, cut-off >64.4 %).
Hospital, Zagreb, Croatia Interobserver agreement was good and independent of the level of exper-
tise. In the DSA positive cohort, the risk groups proved to be an early and
Background & Objectives: Alport spectrum disorders are genetically independent prognostic marker of poor graft function.
heterogenic disorders caused by COL4A3, COL4A4 or COL4A5 muta- Conclusion: Addition of a CD68 stain to the routine analysis of kidney
tions. Aim of this study was to correlate mutational status with transplant biopsies provides additional diagnostic and prognostic information.
pathohistological and clinical characteristics of patients with novel
COL4A4 splice site mutation.
Methods: Four patients, three male and one female, from four unrelated OFP-01-015
families (age range 2-61 years) with pathohistological diagnosis of Alport Is it possible to predict parameters of the Oxford classification in
syndrome (AS) or thin glomerular basement membrane nephropathy primary IgA nephropathy/Berger's disease from clinical laboratory
(TBMN) were tested by NGS sequencing (Illumina MiSeq platform) data?
for COL4A3, COL4A4 and COL4A5 genes mutations. Testing was per- C. Silva1, M.L. Monteiro1, M. Vieira1, L. Araújo1, L.H. Pereira1, L.
formed as a part of project ''Genotype-Phenotype correlation in Alport’s Araújo2, L. Rocha1, J. Machado1, M. Reis1
1
syndrome and Thin Glomerular Basement Membrane Nephropathy'' Institute of Biological and Natural Sciences, Discipline of General
founded by the Croatian Science Foundation. Novel splice acceptor path- Pathology, Federal University of Triangulo Mineiro, Uberaba, Minas
ogenic variant c.193-2A>C was found in COL4A4. The youngest patient Gerais, Brazil, 2 Faculty of Mathematics of Federal University of
was homozygous and others were heterozygous for the mutation. Uberlândia, Uberlândia, Minas Gerais, Brazil
Results: All the patients presented with proteinuria and haematuria at the
time of kidney biopsy. The homozygous patient in light microscopy had Background & Objectives: IgA nephropathy (IgAN), the most common
only increased number of immature glomeruli, while electron microscopy primary glomerulonephritis, has a broad range of histological and clinical
showed typical findings for AS. From the group of heterozygous patients, manifestations. This study assessed sensitivity, specificity and accuracy
two showed focal segmental glomeruloscerosis in light microscopy. of clinical data at the time of biopsy in predicting Oxford classification
Electron microscopy revealed TBMN with focal lamellation in one pa- parameters and investigated if subtypes of segmental glomerulosclerosis
tient, typical AS in second and TBMN in third patient. (FSGS) influence clinical presentation
Conclusion: Diagnostic process of AS spectrum disorders can be challenging. Methods: Renal biopsies from 103 patients with IgAN were analysed
Although genetic testing gives insight into potential disease severity and pro- using ROC curves, univariate and multivariate logistic regression.
vides basis for genetic counselling there is variability in phenotype of disorders Results: Patients were predominantly M0, E0, S1, T3 and C0.
with the same mutation. Renal biopsy remains method that provides informa- Hypertension increases the chance of M1 in 2.54x. For each unit of
tion about degree of renal parenchyma damage. increased creatinine, 2.6x more chances of E1. S1 is predicted by protein-
uria with 75% sensitivity and 90.9% specificity. For each unit of GFR
Supported by Project ''Genotype-Phenotype correlation in Alport’s syn- increase, a reduction of 6% in the chance of T2 comparing to T0. If
drome and Thin Glomerular Basement Membrane Nephropathy'' founded hypertension, 5x more chances of T2 than T0. For each unit of creatinine
by the Croatian Science Foundation. increase, 2.8x more chances of crescents. Creatinine showed 75.8% sen-
sitivity and 75% specificity for C prediction. For each unit of GFR, the
chance of C is reduced by 4%. Hypertension and proteinuria were also
OFP-01-014 related with C. Proteinuria was the only parameter with significative
Glomerular CD68-positive cells - a new prognostic marker in renal difference between S0 and S1 groups. FSGS subtypes related to protein-
transplant pathology uria were cellular and peri-hilar. Subtypes related to podocytopathies
H. Hopfer1, R. Silva2, T. Menter1, M. Lindström3, N. Deigendesch1, C. showed no correlation with clinical data.
Wehmeier4, S. Schaub4 Conclusion: With the future availability of noninvasive methods for diag-
1
Institut für Medizinische Genetik und Pathologie, Universitätsspital nosis of IgAN, predict Oxford classification parameters using clinical data
Basel, Switzerland, 2 Serviço de Anatomia Patológica, Centro will be essential, an approach we showed to be possible. FSGS lesions not
Hospitalar de S. João, Porto, Portugal, 3 Clinical Pathology, Skane related to podocytopathies may also influence clinical parameters.
University Hospital, Malmö, Sweden, 4 Transplantationsimmunologie
und Nephrologie, Universitätsspital Basel, Switzerland
Sunday, 8 September 2019, 08:30 - 12:00, Galliéni 4
Background & Objectives: Transplant glomerulitis is a key feature of OFP-02 | Digestive Diseases Pathology – GI
antibody-mediated rejection. Leukocytes occluding the glomerular capil-
laries define its morphological pattern. It is difficult to recognize and its
scoring only has a fair interobserver agreement. We aimed to determine OFP-02-001
and validate a well reproducible immunohistochemical marker for Becoming a dysplastic Barrett's oesophagus expert: quantification of
glomerulitis, and looked at its prognostic value. expertise and continuous structural education in the set-up of a na-
Methods: Receiver operator curves (ROC) using CD3, CD45, or CD68 tional digital review panel
positive cell counts in the glomeruli of kidney transplant biopsies with M. van der Wel 1 , L. Brosens 2 , K. Biermann 3 , M. Doukas 3 , C.
glomerulitis or without relevant pathology were used to determine cut- Huysentruyt4, A. Karrenbeld5, F. ten Kate6, G. Kats-Ugurlu5, J. van der
offs. Findings were independently validated, tested for interobserver Laan7, I. van Lijnschoten4, F. Moll8, J. Offerhaus2, A. Ooms9, K.
agreement, and compared to other rejection patterns. The prognostic val- Seldenrijk10, M. Visser11, J. Tijssen12, J. Bergman12, S. Meijer1
1
ue was investigated in a cohort of patients (n=95) transplanted in the Department of Pathology, Amsterdam UMC, University of Amsterdam,
presence of donor-specific antibodies (DSA). The Netherlands, 2 University Medical Center Utrecht, The Netherlands,
 Virchows Arch

3
Erasmus MC, The Netherlands, 4 PAMM, The Netherlands, Klintrup-Mäkinen score and worse overall survival (p=0.043). Of the two
5
Department of Pathology University of Groningen, The Netherlands, features, BD was independent of grade in multivariate survival analysis.
6
UMCU, The Netherlands, 7 Haga Hospital, The Netherlands, 8 Isala, Conclusion: Both features are reflective of a more aggressive tumour.
The Netherlands, 9 Pathan, The Netherlands, 10 Pathology-DNA, However, the associations of G3 with histological subtype, sidedness and
The Netherlands, 11 Symbiant, The Netherlands, 12 Amsterdam mismatch-repair deficiency suggest a process that differs from BD, which
University Medical Centers, The Netherlands is hypothesized to reflect epithelial-mesenchymal transition (EMT).
Tumour grade and BD should be considered different parameters in co-
Background & Objectives: Assessment of dysplastic Barrett’s oesoph- lorectal cancers.
agus (BE) biopsies is subject to observer variability. Subsequently, most
guidelines require review of dysplastic cases by BE-expert pathologists
and in the Netherlands, we therefore set up a national digital BE-expert OFP-02-003
review panel. Goal is to stratify BE patients according to progression risk, Expression of the inhibitory receptor CD94/NKG2A on CD8+
leading to lower health care costs. So far, no definition of 'BE-expert' tumour-infiltrating lymphocytes in colorectal cancer: a new promis-
pathologist exists. We aimed to set up a review panel, objectively quantify ing druggable immune checkpoint in a context of HLA-E/
expertise and homogenize assessment within a group of BE-pathologists. b2microglobuline overexpression by tumour cells
Methods: Fifteen pathologists individually assessed 5x60 digitized BE C. Bossard1, J. Eugene2, N. Jouand2,3, K. Ducoin2, R. Oger2,3, J.
biopsy sets, including the complete spectrum of BE-pathology with both Podevin4, J. Bennouna4,5, S. Bezieau6,7, C. Volteau7, W. El Alami
study- and real time panel review cases. At study entrance, participating Thomas8, O. Kerdraon9, P. Fourquier10, E. Thibaudeau9, A. Jarry2,3, J.
pathologists were heterogeneous in experience, work setting (community Mosnier11,5, N. Gervois2,3
1
or academic hospital) and weekly BE workload. Outcomes measured Pathology Department, University Hospital, Nantes, France,
were observer agreement; concordance; % of cases diagnosed ‘indefinite 2
CRCINA, INSERM, Universitè d'Angers, Universitè de Nantes,
for dysplasia’ or significantly misdiagnosed cases. All outcomes were Nantes, France, 3 LabEx IGO «Immunotherapy, Graft, Oncology»,
compared to benchmark values, constructed using a gold standard Nantes, France, 4 Institut des Maladies de l'Appareil Digestif,
diagnosis. Oncologie Digestive, Centre Hospitalier Universitaire Hôtel Dieu,
Results: In 5 years, 15 pathologists assessed 31500 slides, yielding 6000 France, 5 Universitè de Nantes, Facultè de Mèdecine, France, 6 Service
individual case diagnoses. After completing each set, pathologists de Gènètique Mèdicale, Centre Hospitalier Universitaire Hôtel Dieu,
discussed discrepant cases in face to face group discussions, receiving Nantes, France, 7 Plateforme de Biomètrie, CHU de Nantes, France,
8
individual performance feedback before proceeding to the next study Institut d'Histopathologie, Nantes, France, 9 Dèpartement de Biologie
step. Over a timeline of 5 study sets, the pathologist group evolved from des Cancers, Institut de Cancèrologie de l'Ouest, Nantes, France,
10
heterogenous reviewers to a homogenous BE-expert pathologist group Service de Chirurgie Viscèrale et Digestive, Hôpital privè du
that adhered to the values for all benchmark quality criteria. Confluent, Nantes, France, 11 Service d'Anatomie et Cytologie
Conclusion: All pathologists met the benchmark values for all outcomes. Pathologiques, Centre Hospitalier Universitaire Hôtel Dieu, Nantes,
We show that expertise is reproducible and can be quantified, using a struc- France
tured approach to form a national digital BE-review panel. A heterogeneous
pathologist group evolved into a homogeneous expert panel with reproduc- Background & Objectives: We previously demonstrated that HLA-E/
ible case assessments, greatly improving patient care. This training program β2m overexpression by tumour cells in colorectal cancer (CRC) is asso-
can be applied to other challenging diagnostic pathology areas. ciated with an unfavorable prognosis (Bossard et al, 2012). However, the
expression of its specific receptor CD94/NKG2 by intraepithelial tumour-
infiltrating lymphocytes (IEL-TIL), the exact phenotype and function of
OFP-02-002 CD94/NKG2+ TILs as well as the relation with the microsatellite status
Are tumour budding and tumour grade the same in colorectal (MS) of CRC remain unknown.
cancer? Methods: Two independent cohorts of CRC (retrospective n=234; pro-
I. Zlobec1, H. Dawson1, A. Blank1, J. Bokhorst2, I. Nagtegaal3, A. Lugli1 spective n=28) were analysed in the current study. On the retrosepctive
1
University of Bern, Switzerland, 2 Radboud University Medical Center, cohort, we assessed IEL-TILs density (CD8, NKp46, CD94) and expres-
The Netherlands, 3 Department of Pathology, Radboud University sion profile of HLA-E and β2m by immunohistochemistry on Tissue
Medical Centre, Nijmegen, The Netherlands microarray in relation with the clinicopathological and molecular charac-
teristics. The prospective cohort allowed us to isolate TILs from primar
Background & Objectives: Both tumour budding (BD) and tumour tumour, analyse ex vivo their precise phenotype by flow cytometry, and
grade are considered additional prognostic factors in colorectal cancer. confirm the inhibitory function of CD94/NKG2A receptor expressed by
The International Tumour Budding Consensus Conference (ITBCC) CD8+ TILs using a redirected lysis assay.
guidelines state that these two features are not the same. Whereas tumour Results: HLA-E/β2m was preferentially overexpressed in microsatellite
budding is defined by single cells/small cell clusters up to four cells, instable CRC compared with microsatellite stable CRC (45 % vs 18 %
tumour grade is determined by the degree of glandular formation. The respectively, p=0.0001). HLA-E/β2m+ CRC, irrespective of the
aim was to determine the correlation of both features and the association Microsatellite status, were significantly enriched in CD94+ IEL-TIL
of each with clinicopathological data. whose density was independently associated with a worse overall survival
Methods: A retrospective cohort of 511 patients with full histopatholog- (p=0.03). Ex vivo analyses demonstrated that CD94+ TILs mostly
ical and outcome data were reviewed for tumour grade (G1, G2, G3) and corresponded to CD8+ αβ T cells, and mainly co-expressed a functional
tumour budding (ITBCC: BD1, BD2, BD3). Statistical associations were NKG2A inhibitory chain.
analysed in univariate and multivariate analysis. Conclusion: Our results strongly suggest that tumour cells of CRC, es-
Results: Tumour grade and BD were correlated (p<0.0001). 34% of G3 pecially MSI CRC, via aberrant overexpression of HLA-E/β2m, contrib-
cases were BD1. Only one G1 case was BD3. Both grade and BD were ute to paralyze the antitumour immune attack in engaging the inhibitory
associated with more advanced TNM stage, lymphatic and vascular inva- CD94/NKG2A receptor on CD8+ IEL-TILs.Therefore, HLA-E/β2m -
sion (p<0.0001, all). High tumour grade was additionally linked to mucin- CD94/NKG2A represents a promising new inhibitory immune check-
ous histological subtype, right-sidedness and mismatch-repair deficiency point involved in CRC that could be targeted with the recently generated
whereas higher BD score correlated with perineural invasion, lower humanized anti-NKG2A monoclonal antibody.
Virchows Arch

DHOS (PROG/09/03), Ligue contre le cancer, DHU Oncogreffe, Nantes surgery. SOX9 expression was evaluated by immunohistochemistry
(RC14-0416-1), Cancéropôle Grand Ouest (Amgen RC16-0212-1). Plan using a 4-tier grading system for intensity of expression (0=none,
Cancer 2009-2013 AAC 1=low, 2=moderate, 3=high) and percentage of SOX9-positive cells.
Demographics, tumour characteristics and outcomes were extracted from
medical records and SPSS (Chicago, IL) was used for statistical analysis.
OFP-02-004 Results: In this study, the mean age of patients was 60.4 (32-72). 80% of
E-learning for instruction of scoring the tumour-stroma ratio (TSR) them were male and the majority were Caucasians (76%). 92% of patients
in colon carcinoma amongst international pathologists, as part of the had at least T3 tumours and 68% had stage III disease. Mean diameter of
UNITED study. tumour pre-treatment was 4.95 cm (3-8) and post-radiation was 2.79 (0.4-
M. Smit1, G. van Pelt1, R. Al Dieri2, R. Tollenaar1, H. van Krieken3, W. 5.3). Down-staging occurred in 15 (60%) patients, but only 2 (8%) had
Mesker1 on behalf of the UNITED group1 complete pathologic response. Six (24%) patients had positive nodes
1
Leiden University Medical Centre, The Netherlands, 2 European identified after surgery. In cancer specimens, 96% were graded as mod-
Society of Pathology, Belgium, 3 Radboud University Medical Centre erate or high expression before radiation, which changed to 88% after
Nijmegen, The Netherlands radiation. Percentage of SOX9 positive cells is also different with 91.7%
of cells positive before radiation and 66.7% after radiation. The high
Background & Objectives: The tumour-stroma ratio (TSR) was validat- percentage of SOX9 positive cells and moderate or high expression were
ed by many international research groups and showed to be an indepen- both associated with complete pathologic response (p=0.008). Reduced
dent prognostic parameter for survival. The UNITED study (Uniform tumour size after radiation occurred in all patients including cases with
Noting for International application of the Tumour-stroma ratio as Easy decreased intensity of SOX9 expression (p=0.005), however decreased
Diagnostic tool) is developed to validate the TSR prospectively as addi- SOX9 expression tends to occur in patients with larger tumour size.
tional high-risk parameter next to the TNM classification. Although not statistically significant, decrease in percent positivity and
As part of the UNITED study, a training and reproducibility study for intensity after radiation both trended toward significance for distant re-
scoring the TSR is set up using an E-learning module. currence (p=0.07). SOX9 expression was not associated with other tu-
Methods: The E-learning started with an auto-instruction based on in- mour characteristics or oncologic outcomes.
struction video and written protocol. Thereafter, three sets of 40 colon Conclusion: Our findings indicate that percentage of SOX9 positivity
carcinoma cases were scored for TSR. Between the second and third set a and moderate or high intensity of expression in rectal cancer specimens
wash-out period of 2 months was set. Inter- and intra-observer agreements decrease after radiation. Oncologic outcomes appear to be improved
were calculated to evaluate reproducibility. when intensity of expression and percent positivity remain elevated, for
After completion of the E-learning, pathologists will continue scoring the example, in complete pathologic response. When expression decreases
TSR in the prospective study to validate the TSR prospectively in a cohort after radiation, distant recurrence and larger post-radiation tumour size are
comprising 1500 patients colon cancer stage II and III. more common. Although its role remains controversial, our findings sug-
Results: Twenty-two hospitals from 17 countries are participating in the gest that SOX9 may be an important marker and potential target for
UNITED study. Forty-one colorectal cancer pathologists started the E- tumour response and oncologic outcomes for rectal cancer after radiation.
learning, of whom 70% (n=28) finished the whole cycle so far. The
median kappa score was κ=0.72 for the training set, κ=0.77 for the test
set and κ=0.78 for the repetition test set. The median intra-observer OFP-02-006
agreement is κ=0.78. Poor clinical significance of tissue calprotectin levels in bowel mucosa
Conclusion: E-Learning is an effective method to instruct pathologists for the prediction of complicated course of the disease in children
for scoring the TSR. The results improved from the first to the second set with ulcerative colitis. A pilot study
and did not fall back in period of time for the last set. After validation of O. Fabian1, O. Hradsky1, T. Lerchova1, F. Mikus1, J. Zamecnik1, J.
the TSR in the prospective study, the TSR will be ready to use in daily Bronsky1
1
practice. Motol University Hospital, Czech Republic

The UNITED study is granted by The Dutch Cancer Society or ‘KWF Background & Objectives: To evaluate the usefulness of immunohisto-
Kankerbestrijding’ (project 10174) and the ‘Stichting Fonds Oncologie chemical (IHC) detection of tissue calprotectin (T-CPT) in bowel mucosa
Holland’. in children with ulcerative colitis (UC). We focused at correlation of T-
CPT with levels of faecal CPT (F-CPT) and endoscopic and microscopic
disease activity at the time of diagnosis and tested whether T-CPT could
OFP-02-005 serve as predictor of complicated course of the disease.
For better or worse: clinical correlation of SOX9 expression in irra- Methods: Forty-nine children with newly diagnosed UC between 6/2010-
diated rectal cancer 1/2018 entered the study. Endoscopic activity was objectivised using the
X. Duan1, B. Trac1, X. Ding1 Ulcerative Colitis Endoscopic Index of Severity (UCEIS), clinical activity
1
Loyola University Medical Center, USA by Paediatric Ulcerative Colitis Activity Index (PUCAI) and microscopic
activity by Geboes and Nancy score. The IHC staining for CPT antigen was
Background & Objectives: Sex-determining Region Y box 9 (SOX9) performed on bioptic samples from 6 bowel segments and the number of
has been shown to play a fundamental role in epithelial-mesenchymal CPT+ cells was counted per 1HPF. During the minimal follow-up of 12
transition (EMT) and is dysregulated in colorectal cancer. Its role in car- months we searched for presence of particular complications.
cinogenesis remains controversial since SOX9 has been associated with Results: As outcome for Cox regression model we used tree endpoints:
both positive and negative prognostic factors in multiple cancers. Sox9 A) Acute Severe Colitis, colectomy, anti-TNF treatment; B) A+ systemic
expression and clinical correlation are also not clear in irradiated rectal corticotherapy; C) B+ systemic 5-aminosalicylic acid therapy. Neither
cancer. The objective of this study is examining the clinical correlation of levels of T-CPT nor values of UCEIS, Geboes or Nancy score predicted
SOX9 expression in irradiated rectal cancer. the given complications. We found F-CPT levels (HR 2.42 and 2.52) and
Methods: Sections from both normal and cancerous tissue were taken PUCAI>40 points (HR 2.98) as predictors of time to endpoints B and C.
before and after radiation in 25 patients with locally advanced rectal We found a good correlation between T-CPT levels and Geboes (k=0.65)
cancer who received neoadjuvant chemoradiation therapy followed by and Nancy score (k=0.62).
 Virchows Arch

Conclusion: T-CPT correlated well with microscopic scores. F-CPT and Methods: Between October 2009 and March 2018, we included totally
PUCAI appears to be better predictor of unfavourable outcome in patients embedded oesophagus-cardia resection specimens from 151 consecutive
with UC. patients marked preoperatively for radiation field target volumes after
nCRT with carboplatin/paclitaxel and 41.4Gy radiotherapy (CROSS
Grant Agency of Charles University in Prague [grant number 2120248]. regimen).
Results: According to the Mandard tumour regression grade system,
pCR (ypT0N0) was detected in 18.8% (n=27), whereas 21 patients had
OFP-02-007 nearly no response (TRG 4-5). Of the remaining non-complete
Risk factors for intraductal tumour spread of submucosal gland in responding patients with TRG 2-3 (n=95), residual tumour only in lymph
early squamous cell neoplasia: analysis of endoscopically resected nodes (ypT0N+) was observed in 7.4% (n=7). Among the remaining
specimens patients with ypT1-2, residual tumour was more common in the submu-
I. Chang1,2,3,4, W. Wang5 cosa (18.9%) and muscularis propria (18.9%), while among those with
1
Department of Pathology, School of Medicine, College of Medicine, ypT3-4 it was more often in the adventitia than outside the oesophageal
Taipei Medical University, Taiwan, 2 Department of Pathology, Taipei wall (73.9% vs 7.4%; p < 0.05). In 8.4% residual tumour was found
Medical University Hospital, Taiwan, 3 Department of Pathology, Wan outside the gross tumour volume (GTV), whereas microscopic residual
Fang Hospital, Taipei Medical University, Taiwan, 4 Department of cells were seen outside the clinical target volume (CTV) in 18.9%. In one
Pathology, Shuang Ho Hospital, Taipei Medical University, Taiwan, patient with ypT0N+ residual nodal disease was observed outside the
5
Department of Internal Medicine, E-Da Hospital/I-Shou University, CTV.
Kaohsiung, Taiwan Conclusion: After nCRT, 18.8 % of the EC patients had a pCR, while 7.5
% of the non-complete responders with ypT0 still had residual tumour in
Background & Objectives: The oesophageal gland duct may serve as a the lymph nodes. In one of these ypT0N+ patients the residual tumour
pathway for the spread of early oesophageal squamous cell neoplasia was found outside the CTV.
(ESCN) to a deeper layer. However, the risk factors and significance of
ductal involvement (DI) in patients receiving complete endoscopic sub-
mucosal dissection (ESD) has yet to be investigated. OFP-02-009
Methods: We consecutively enrolled patients with early ESCN who were Mechanotransduction in mice colon tumourigenesis: a pathologically
treated with ESD. The resected specimens were retrospectively reviewed reactivated physiological embryonic mechanosensitive pathway
for the number, morphology, resected margin, distribution and extension E. Farge1, M. Fernandez-Sanchez1, D. Meseure2
1
level of DI, which were then correlated to clinical factors and survival. A Institut Curie - Inserm, France, 2 Platform of Experimental Pathology,
total of 160 lesions were analysed. Totally, 317 DIs in 61 lesions (38.1%) Department of Diagnostic and Theranostic Medicine Institut Curie, Paris,
were identified. Of these, 14 had DIs extended to lamina propria, 17 to France
muscularis mucosae, and 30 to the submucosal layer.
Results: Multivariate logistic regression analysis showed that tumours locat- Background & Objectives: The tumour microenvironment may
ed in the upper oesophagus (OR=2.93, 95%CI,1.02-8.42), large tumour cir- contribute to tumourigenesis due to mechanical forces such as fi-
cumferential extension (OR=5.39, 95%CI,1.06-27.47), advanced tumour in- brotic stiffness or mechanical pressure caused by the expansion of
vasion depth (OR=4.12, 95%CI,1.81-9.33) and numerous Lugol-voiding hyper-proliferative cells. Here, we explore the contribution of the
lesions in background mucosa (OR=2.65, 95%CI,1.10-6.37) were risk fac- mechanical pressure exerted by the tumour growth onto non-
tors for DI. The maximally extended level and total number of ducts involved tumourous adjacent epithelium.
were significantly correlated with the depth of cancer invasion (P<0.05). The Methods: We thus developed a method that allows to deliver de-
patients with DI had worse overall survival and recurrence-free survival (both fined mechanical pressure in vivo, by subcutaneously inserting a
P≤0.015) than those without DI after successful ESD. dorsal magnet close to the mouse colon. The implanted magnet
Conclusion: DI is not uncommon in early ESCN. Due to the maximal generated a magnetic force on ultra-magnetic liposomes (UML),
ablation depth of radiofrequency ablation (RFA) limited to muscularis stabilized in the mesenchymal cells connective tissue surrounding
mucosae, these deeply extended ducts will not be eradicated, which colonic crypts after intravenous injection. The pressure induced
may potentially cause tumour recurrence or even buried cancer. Our find- magnetically quantitatively mimicked the endogenous early tumour
ings may guide clinical decision making with regards to endoscopic treat- growth stress in the order of 1kPa.
ment and surveillance. Results: In the early stage of mouse colon tumour development in the
Notch+ APC1638N/+ mouse model, we observed mechanistic pressure
stress in the non-tumourous epithelial cells caused by hyper-proliferative
OFP-02-008 adjacent crypts overexpressing active Notch, associated with increased
Site of residual oesophageal cancer after neo-adjuvant chemoradio- Ret and β-catenin signalling.
therapy with regard to the anatomical layers and radiation target Exertion of magnetic pressure mimicking that of tumour growth led to
volumes at histopathologic examination rapid Ret activation and downstream phosphorylation of β-catenin on
Z. Faiz1,2, V. Mul3, A. Karrenbeld2, G. Kats-Ugurlu2, J. Plukker1, K. Tyrosine 654, which impairs its interaction with the E-cadherin in
Muijs3 adherens junctions, and which was followed by β-catenin nuclear trans-
1
Department of Surgical Oncology University of Groningen, The location after 15 days. As a consequence, elevated expression of β-
Netherlands, 2 Department of Pathology University of Groningen, The catenin target genes was observed at one month, together with crypt
Netherlands, 3 Department of Radiotherapy University of Groningen, The enlargement accompanying the formation of early tumourous aberrant
Netherlands crypt foci (ACF).
Conclusion: Mechanical activation of the tumourigenic β-catenin path-
Background & Objectives: Neoadjuvant chemoradiotherapy (nCRT) way suggests unexplored modes of tumour propagation based on me-
followed by surgery leads to a significant rate of pathologic complete chanical signalling pathways in healthy epithelial cells surrounding the
response (pCR) in patients with curatively treatable oesophageal cancer tumour, which may contribute to tumour heterogeneity1-3.
(EC). EC patients with a clinical complete response are probably candi- We found the mechanotransductive phosphorylation of the Y654 site of
dates for a watchful wait strategy in the near future. b-catenin by the first morphogenetic movements of embryogenesis,
Virchows Arch

leading to its release into the cytoplasm and nucleus, as due to its me- OFP-02-011
chanical opening to Src family kinase phosphorylation4, and involved and Cell line-derived xenografts: a possible in vivo model to investigate
conserved in earliest mesoderm and endoderm differentiation in the ver- tumour budding in colorectal cancer
tebrate zebrafish and un-vertebrate Drosophila5. I. Zlobec1, L.M. Georges2, O. de Wever3, J.A. Galván4, H. Dawson1, A.
We thus propose the pathological re-activation of the mechanosensitive Lugli1, P. Demetter5
β-catenin signalling in tumourigenesis physiologically involved in early 1
University of Bern, Switzerland, 2 Department of Pathology, Erasme
embryonic patterns differentiation. Hospital, Universitè Libre de Bruxelles, Belgium, 3 Laboratory of
1 Whitehead, J. et al. Mechanical factors activate beta-catenin-dependent Experimental Cancer Research, University of Ghent, Belgium,
4
oncogene expression in APC mouse colon. HFSP journal 2, 286-294, University of Bern, Institute of Pathology, Switzerland, 5 Department
doi:10.2976/1.2955566 (2008). of Pathology, Institut Jules Bordet, Universitè Libre de Bruxelles, Belgium
2 Fernandez-Sanchez, M. E., Barbier, S. & al., e. Mechanical induction of
the tumourogenic β-catenin pathway by tumour growth pressure. Nature Background & Objectives: Tumour budding is recognized as a major
(In press). adverse prognostic factor in colorectal cancer. Standard H&E, immuno-
3 Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C. & Farge, E. histochemistry, laser capture microdissection and RNA or DNA sequenc-
Mechanotransduction's Impact in Animal Development, Evolution, and ing have been performed to help elucidate the mechanisms of tumour
Tumourigenesis. Annu Rev Cell Dev Biol, doi:10.1146/annurev-cellbio- budding, but only capture a snapshot of the process. The aim of this study
102314-112441 (2015). is to determine whether cell line-derived mouse xenografts (CDX) could
4 Roper, J. C. et al. The major beta-catenin/E-cadherin junctional binding represent a suitable in vivo model of tumour budding.
site is a primary molecular mechano-transductor of differentiation in vivo. Methods: Tumours from mouse xenografts generated by orthotopic im-
eLife 7, doi:10.7554/eLife.33381 (2018). plantation of different cell lines (HCT-8, HT-29, COLO320, RKO) were
5 Brunet, T. et al. Evolutionary conservation of early mesoderm specifi- evaluated for tumour budding. HT-29 and HCT-8 were representative of
cation by mechanotransduction in Bilateria. Nature communications 4, high-grade and low-grade budders and selected for next-generation
doi:10.1038/ncomms3821 (2013). Tissue Microarray (ngTMA) construction by sampling intratumoural
INCA grant # PLBIO13-172 FRM grant # DEQ20150331702 ANR grant (ITB) and peritumoural (PTB) budding. Immunohistochemistry for E-
# 16CE14002801) cadherin, β-catenin, Ki-67, ZEB1, SNAIL1, Caspase-3, TWIST1 and
double-staining for Vimentin/Ku80 were performed. A control group of
52 patients with low- and high-grade budding was included.
OFP-02-010 Results: Comparing HT-29 CDX and human high-grade budding cases,
The prognostic impact of the colorectal cancer microenvironment PTB counts were 45 and 30 buds/TMA core (p=0.07) and ITB counts
components and their spatial relationships were 22.6 and 12 buds/TMA core (p=0.0099). In HT-29 CDX and high-
I.P. Nearchou1, C.G. Gavriel2, D.J. Harrison2, P.D. Caie2 grade budding cancers, ITB and PTB were significantly correlated
1
University of St Andrews, United Kingdom, 2 School of Medicine, (r=0.45; r=0.62). Ku80 staining in the CDX model confirmed the human
University of St Andrews, United Kingdom origin of cells identified as buds. Immunohistochemistry profiles were
similar in CDX and human cancers.
Background & Objectives: The tumour immune infiltrate contributes Conclusion: Tumour budding occurs to various degrees in CDX mouse
majorly in tumour progression and patient survival outcome. However, models and is morphologically and phenotypically similar to budding in
the aggressive potential of colorectal cancer cannot be manifested without human colorectal cancer. Such an in vivo model will help to investigate
capturing the interplay between cancer cells and the host’s immune re- the more functional aspects related to the tumour budding process.
sponse. In this study, we examined the prognostic value of tumour buds
(TBs) reflecting tumour progression, the tumour immune infiltrate and
their spatial relationships in stage II colorectal cancer. OFP-02-012
Methods: Two multiplex immunofluorescence antibody panels compris- Comprehensive molecular analysis of recurrence in
ing CD3+, CD8+, CD68+, CD163+, pancytokeratin and Hoechst were gastrooesophageal adenocarcinoma
applied in two sequential whole slide images (n=232). Cell quantification F. Renaud1, G. Piessen1,2, M. Figeac3, C. Dejeante4, M. Messier4, L.
and the evaluation of their spatial interactions was performed through Delattre 5 , A. Adenis 6 , D. Chatelain 7 , C. Boulagnon-Rombi 8, C.
automated image analysis. Exported features were processed through Eveno1,2, I. Van Seuningen2,3, C. Mariette1,2, E. Leteurtre1,2, M.
machine learning algorithms for the development of a new prognostic Buisine1,2
1
risk model. CHU, Univ.Lille, France, 2 Inserm UMRS 1172, France, 3 Univ.Lille,
Results: TB (p=0.001) and lymphocytic density (p<0.001) were France, 4 CHU, Inserm UMRS 1172, Lille, France, 5 CHU, Lille, France,
6
found to be prognostically significant independently. Though, Montpellier Cancer Institute, Inserm U1194, France, 7 Amiens
their integration with their spatial relationship (p<0.001) reported University Hospital, Amiens University, France, 8 Reims University
a more significant cohort stratification than the clinical gold stan- Hospital, Reims University, France
dard of pT stage (p=0.003) in a training cohort (n=114) and two
independent validation cohorts (n=56 and n=62). Inclusion of the Background & Objectives: Gastrooesophageal adenocarcinomas (GEAs)
macrophage cell data in a new prognostic model allowed the low- are characterised by recurrences in more than 50% of patients. There is a
risk patients to be identified with 100% sensitivity. No clinico- critical need to understand the molecular features of the recurrence to interfer
pathological features were selected for any of the models by the more effectively in the late stages of cancer progression. The main objective
machine-learning workflow. of the study was to assess the molecular profile of GEAs recurrence and to
Conclusion: Here we demonstrate how the integration of automated im- compare this profile with the one of the primary tumour.
age analysis and machine learning in studying the tumour heterotypic Methods: A total of 84 untreated, surgically resected GEAs with 91
microenvironment can lead to the more accurate stratification of patients paired samples of metachronous distant and/or locoregional metastases
with stage II colorectal cancer. were included. Recurrence was defined as local, locoregional or distant
metastasis occurring at least 6 months after the first histological diagnosis.
Funding for the study was provided by Medical Research Scotland, and Expression of HER2, EGFR, c-MET, ALK, ROS, EBV, MLH1, PMS2,
Indica Labs, Inc., provided in-kind resource. MSH2, MSH6, p53, E-cadherine, ARID1A was analysed by
 Virchows Arch

1
immunohistochemistry/in situ hybridization. Chromosomal, genomic and University of Health Sciences, Department of Pathology, Turkey,
2
methylation alterations were analysed using CGH array, NGS and bisul- Acıbadem University, Department of Pathology, Turkey, 3 University of
fite pyrosequencing, respectively. Health Sciences, Istanbul Health Practice and Research Hospital,
Results: Frequent expression of tyrosine kinases receptors HER2, c-MET Department of Pathology, Turkey
and EGFR was detected in the recurrence (42% versus 29% in the primary).
Most tumours displayed chromosomal instability (65%), mesenchymal pro- Background & Objectives: It is well established that colorectal can-
file including genome stable tumours (24%), microsatellite instability (7%) cer develops from a series of precursor epithelial polyps, including
and EBV (4%). Chromosomal alterations were more frequent in the recur- tubular adenomas (TA), villous/tubulovillous adenomas (VA/TVA),
rence. Frequently mutated genes were TP53 67%, CDH1 21%, ARID1A sessile serrated adenomas (SSA) and traditional serrated adenomas
14%, SMAD4 13%, and PIK3CA 10%. Interestingly PI3KCA mutation (TSA). The criteria for diagnosing adenomas are determined.
was associated with the recurrence in GEAs. Methylation profiles were However, there can be overlapping feautures within these lesions.
similar between primary and recurrence. The aim of this study is to settle the characteristics and overlapping
Conclusion: Molecular profiles are different between primary and recur- features of colonic adenomas.
rence in GEAs. This should be considered to improve treatment of pa- Methods: A total of 140 adenomas (70 conventional adenomas, 35
tients with advanced disease. SSA/P and 35 TSA) H&E stained slides were retrieved from our
archive. All these cases were reclassified according to the criteria.
Supported by SIRIC ONCOLille, Ligue contre le cancer, Lille University Demographics were obtained from charts. Macroscopically, whether
Hospital grants for young researcher the adenoma possesses sessile or polypoid structure; microscopical-
ly filliform and villous architecture of the lesion and occurrence of
serration, ectopic crypt, eosinophilic cytoplasm, silender nucleous,
OFP-02-013 dilatation of crypt base, presence of mucinous hypersecretion on the
Confocal microscopy as an alternative microscopic diagnosis that base and surface, adenomatous dysplasia, serrated dysplasia and the
saves time and money for pathology departments: pilot study on degree of dysplasia of the lesions were examined. Current criteria
colorectal polyps for each lesion first investigated in the binary system (available /
J. Guerrero1, G. Fernandez-Esparrach2, J. Perez-Anker3, H. Cordova2, I. unavailable) and in quartet system (0: <10% 1: 10-25% 2: 25-75%
Archilla1, A. Garcia-Herrera1, M. Pellise2, A. Gines2, S. Puig3, J. 3: 75% and above). Thirteen cases with multiple parameters belong-
Malvehy3, M. Cuatrecasas4 ing to each lesion were named as hybrids. KRAS, NRAS, BRAF
1
Pathology Department, Hospital Clinic. University of Barcelona, Spain, mutation, MSI analysis and MLH1 promoter methylation analysis
2
Gastroenterology Department, Hospital Clinic. University of Barcelona, were performed in 50 of the cases that have additional non-
Spain, 3 Dermatology Department, Hospital Clinic. University of neoplastic control tissue.
Barcelona, Spain, 4 Pathology Department, Biomedical Diagnostic Results: The diameter of the lesion was found to be smaller in SSAs.
Center (CDB), Hospital Clinic of Barcelona, Spain Macroscopically sessile configuration was seen in SSAs and hybrid
group, only small percentage of the other lesions show sesile structure
Background & Objectives: Colorectal cancer (CRC) screening (p< 0, 001). The presence of dilatation of crypt base, serration and mu-
programmes have accomplished a significant reduction in mortality caused cinous hypersecretion was the most descriptive findings in SSAs (p< 0,
by this disease. Colonoscopy, as an early cancer detection procedure, allows 001). Serration, ectopic crypt, and eosinophilic cytoplasm are distinctive
the identification and removal of polyps for the gold-standard histological features for TSAs (p< 0, 001). Adenomatous dysplasia was definitive
analysis. The increasing number of colonoscopies has created bottlenecks in feature of TA/VA/TVAs. Serration was seen in 50% of TA/VA/TVAs
pathology departments due to the huge number of samples to be analysed. and they had ectopic crypts in 23 cases. But in most of the cases with
We aim to use alternative ways of diagnosis to overcome such bottlenecks. such features less than 25% of the adenoma displayed those characteris-
Methods: In this pilot study, we analysed by conventional histology and tics. At least focal adenomatous dysplasia was also seen in 20 of SSAs
confocal microscopy 20 polyps from 12 patients. Real time scanning of the and 22 of TSAs. Serrated dysplasia was seen in 10% of the TA/VA/TVAs.
tissue was made with the confocal laser microscope VivaScope® 2500M- BRAF mutation was found in 6 SSA/P , 4 TSAs and 1 hybrid case. The
G4TM. Afterwards, conventional histopathologic process was performed. KRAS mutation was detected in 11 TA/VA/TVAs, 2 SSA/P, 6 TSAs and 8
Confocal images were reviewed by three pathologists blind to the haematoxylin hybrid cases. NRAS mutation and MSI were detected in none of the
and eosin (H&E) results. Diagnosis with both methods were compared. cases. MLH1 promoter methylation was seen in 4 TA/VA/TVAs, 4
Results: Eighteen (90%) polyps were tubular adenomas and 2 were ses- SSAs and 2 TSAs.
sile serrated adenomas. Confocal diagnosis was reliable and concordant Conclusion: All histopathological findings can be seen in all types of
with H&E in 100% cases, but in 3 cases (15%) some histological details adenomas. This showed that none of these parameters are particular to a
were missed due to image resolution issues. lesion. In most of the cases, the unexpected feature was present in less
Conclusion: Confocal microscopy allows whole scanning of the tissue in than 25% of the lesion. Thus, the value 25% can be used as a cut off. But
real time and does not interfere with a subsequent pathological analysis. It is a there are a small number of cases which show unexpected features cov-
promising tool with a high reliability and reproducibility compared to gold ering more than 25%. In addition, in molecular analysis of the cases,
standard diagnostics. Its main advantages are the time saving (2-5 minutes) unexpected mutations were detected. This can be an evidence of mixed/
compared to conventional histopathology analysis, and limited required per- hybrid lesions.
sonnel. This alternative morphology-based diagnostic method may contribute
to reduce the rising workload in pathology departments derived from CRC University of Health Sciences Scientific Research Project
screening programmes and bring significant economic savings.

OFP-02-015
OFP-02-014 How many biopsies are needed to assess the Peritoneal Regression
Histopathological and molecular features of adenomatuous and ser- Grading Score (PRGS) in peritoneal metastasis?
rated colon adenomas, characteristics and overlapping features, W. Solass1, D. Nann1, J. Steinke1, G. Nadiradze2, P. Horvath2, R.
challenges in the nomenclature Archid2, H. Bösmüller1
B. Bambul Sıgırcı1, I. Yılmaz1, S. Erdamar Çetin2, E. Yarıkkaya1, M. 1
Institute of Pathology and Neuropathology, University Hospital
Cin3, E. Pasaoglu1, B. Yeni1, N. Dursun3 Tuebingen, Eberhard-Karls-University Tuebingen, Germany, 2
Virchows Arch

Department of General and Transplant Surgery, University Hospital A benign diagnosis was confirmed in 15 of 23 cases. Three cases were
Tuebingen, Eberhard-Karls-University Tuebingen, Germany diagnosed as noninvasive follicular thyroid neoplasm with papillary-like
nuclear features (NIFTP), while 5 cases represented classic papillary car-
Background & Objectives: Peritoneal metastasis (PM) are associated cinoma (n=2) and follicular carcinomas (n=3). The NPV in our series was
with a poor prognosis and a median survival of 3- 6 months. Multimodal only 78.2% if NIFTP was considered a benign lesion and 65.2% when
therapy approaches especially intraperitoneal chemotherapy is increas- NIFTP is included as a malignant lesion.
ingly used. Therefore repetitive peritoneal biopsies are obtained to assess Conclusion: The NPV of ThyroSeq® is lower than reported previously
tumour response. 2016 a group of European pathologists proposed a and a negative ThyroSeq® result should be correlated with other clinico-
regression grading Score for PM- the Peritoneal Regression Grading radiological findings, particularly, in institutions with a high cancer prev-
Score (PRGS). This 4-tied score evaluates therapy response of peritoneal alence.
metastases (PM) of various origin and has been validated as a reproduc-
ible and useful tool in a multicentric comparative study. But the number
of biopsies needed for reliable assessment of tumour response is still OFP-03-002
unclear. Ultrasound guided fine needle aspiration of thyroid: inadequacy rate
Methods: We performed a retrospective analysis of 210 laparoscopies with rapid on-site evaluation
in 89 patients with PM of various origins. In these patients routinely C. Sebastiano1, O. Lin1, J. Girshman1, D. Buonocore1, J. Cohen1
1
4 biopsies from all 4 abdominal quadrants were taken. The analysis Memorial Sloan Kettering Cancer Center, USA
of the 4-tied PRGS was performed by an independent pathologist.
Statistical evaluation concerning the needed number of biopsies and Background & Objectives: Recent meta analysis data in the literature has
the loss or gain of information in the clinical framework has been shown an average inadequacy rate for thyroid ultrasound guided fine needle
evaluated. aspiration (UFNA) of 13%. We investigated the inadequacy rate for UFNA
Results: Out of 246 histological examinations, 120 (95,2%) showed recently performed at our institution with rapid on site evaluation (ROSE).
agreement in ≥ 2 biopsies, 37 (29,3%) in ≥ 3 biopsies and only 18 Methods: We searched the electronic medical record for cases of thyroid
(14.2%) in all 4 biopsies. The diagnostic reference (gold standard) was UFNA performed at our institution over one year. Procedures were per-
definded as the PRGS calculated from 4 biopsies. The mean loss of formed by interventional radiologists or interventional cytopathologists
information was 0.29 ± 0.11 PRGS points with 3 biopsies and 0.50 ± and all underwent ROSE by a cytotechnologist and cytopathologists
0.17 with 2 biopsies. 49 patients with repeated laparoscopies were eligible using telecytology, or by the cytopathologist performing the procedure.
for tumour response assessment: 35 patients (71%) had a histological In most cases a single pass was obtained. Specimens were considered
response (stable or improved PRGS), 14 (29%) a disease progression adequate if at least 6 clusters of 10 follicular cells were present.
(worse PRGS). Mean difference in PRGS between 1st and 2nd laparos- Results: A total of 618 cases were identified; 461 performed by a radi-
copy was 0.23 ± 0.87. PPVand NPVof 3 biopsies for determining tumour ologist and 157 by a cytopathologist. 607 cases were reported at ROSE
response was 100%, resp. 60.9% (95% CI 45.0% to 73.2%) with an and confirmed at sign-out as adequate, 3 as inadequate at ROSE but
accuracy of 81.6%. PPV and NPV of 2 biopsies for determining tumour adequate at sign out, 6 at ROSE and sign-out as inadequate, and 2 as
response was 96.2% (95% CI 78.9% to 99.4%), resp. 56.2% (95% CI adequate at ROSE but inadequate at sign out. The overall inadequacy rate
43.0% to 69.1%) with an accuracy of 77.6% (95%CI 63.4 to 88.2%). was thus 8/618 (1.29%); 6/461 (1.30%) for cases performed by a radiol-
Conclusion: One or two biopsies are not enough to determine PRGS. ogist and 2/157 (1.27%) for those performed by a cytopathologist.
Three biopsies allow proper clinical decision making in 4 out of 5 pa- Conclusion: Thyroid UFNA performed with ROSE substantially reduces
tients. Whenever possible, biopsies should be taken in all abdominal the inadequacy rate at our institution as compared to the average reported
quadrants to assess therapy response in PM. Further investigations on a in the literature. Comparable inadequacy rates are found in procedures
larger cohort needs to be done. performed by radiologists and cytopathologists. By lowering the inade-
quacy rate ROSE reduces the need for re-biopsy, cutting costs and
avoiding additional patient discomfort and anxiety.
Sunday, 8 September 2019, 17:15 - 19:15, Thalie
OFP-03 | Cytopathology
OFP-03-003
The diagnostic utility of zinc finger E-box binding homeobox (ZEB1)
OFP-03-001 for identification of pulmonary sarcomatoid carcinoma in limited
Negative ThyroSeq® genomic testing for indeterminate thyroid nod- specimens
ules: the Memorial Sloan Kettering Cancer Center experience K. Viswanathan1, A. Borczuk1
1
D. Buonocore1, O. Lin1, J. Cohen1 New York Presbyterian-Weill Cornell Medicine, USA
1
Memorial Sloan Kettering Cancer Center, USA
Background & Objectives: Although uncommon, pulmonary
Background & Objectives: The current American Thyroid Association sarcomatoid carcinoma carries a worse prognosis due to poor re-
guidelines suggest the use of molecular studies in the management of pa- sponse to chemotherapy. A histologic spindle and/or giant cell
tients with an indeterminate cytology diagnosis. ThyroSeq®, one of the most component is required for diagnosis, and recent studies implicate
used thyroid molecular tests in the U.S. has a reported high negative predic- Zinc Finger E-box binding Homeobox 1 (ZEB1), a key transcrip-
tive value(NPV). We propose to evaluate the NPVof ThyroSeq® at a major tional regulator of the epithelial-mesenchymal transition program,
cancer center in the U.S. in which the prevalence of malignancy is high. in sarcomatoid progression. However, whether ZEB1 has diagnos-
Methods: Cytology material from 252 thyroid nodules diagnosed as inde- tic use in limited specimens, including cell block (CB) prepara-
terminate were submitted for ThyroSeq® analysis. The results were negative tions, remains unclear.
in 151 of 252 cases and among these cases, 23 nodules were surgically Methods: Sarcomatoid (SARC, n=14), small cell (SCLC, n=8) and large
resected. The ThyroSeq® results were correlated with the surgical diagnosis. cell neuroendocrine carcinoma (LCNEC, n=8), typical (TC, n=9) and
Results: Surgical resection with intent to remove the tested nodule was atypical carcinoid (AC, n=10), squamous cell carcinoma (SQ, n=7), and
performed in 20 of the 23 nodules. They were commonly removed due adenocarcinoma (ADC, n=7) CBs with 71 SARCs, 9 SCLCs, 10
large size, growth or patient’s preference. Three nodules were resected LCNECs, 20 TCs, 21 ACs, 71 SQs, 402 ADCs, 16 large cell carcinoma
due to the presence of a concurrent suspicious nodule. (LCC) and 17 other non-small cell lung carcinoma (NSCLC) surgicals
 Virchows Arch

between 2007-2018 were retrieved. ZEB1 IHC (Sigma) was graded 0 to Background & Objectives: To determine the increase of CIN2+ risk in
3+, with ≥1+ and >5% staining considered positive. HPV-positive women with an abnormal cytology (HPV+/Cyt+) in contrast
Results: Nuclear ZEB1 was seen in 79% SARCs (11/14), 12.5% SCLCs to those with a negative Pap (HPV+/Cyt-) after a 3 year follow-up (FU).
and 12.5% LCNECs (both 1/8), but not in TC, AC, SQ or ADC CBs. In Methods: After cotesting 5,053 women with LBC cytology and
surgicals, 76.1% SARCs (54/71), 12.5% LCCs (2/16), 11.8% NSCLCs APTIMA® HPV, 3,9% (n=155) were HPV+/Cyt+ (ASCUS+) and
(2/17), 30% LCNECs (3/10), 11.1% SCLCs (1/9), 0% TCs (0/20), 0% 5,9% HPV+/Cyt-. The baseline risks for CIN2+ in those groups was
ACs (0/21), 0% SQs (0/71) and 0.2% ADCs (1/402) demonstrated ZEB1 55,2% (48/87) and 14,9% respectively. Women without a high-grade
expression. ZEB1 sensitivity and specificity were 78.6% and 95.9% in lesion were followed for 3 years by cotest and/or biopsy. Statistical risk
cytologic specimens, and 76.1% and 98.4% in surgical specimens, assessment was calculated.
respectively. Results: 58 women from the HPV+/Cyt+ group had adequate 3-year FU.
Conclusion: ZEB1 is sensitive and highly specific in identifying A high-grade (CIN2+) lesion was found in 14 cases (24,1%), all of them
sarcomatoid carcinoma in limited cytologic and surgical specimens. with persistent HPV infection. Abnormal cytology (ASCUS+) was seen
Diagnostic pitfalls include high grade neuroendocrine tumours and large in 13 (92,9%) of them. 54% of HPV+/Cyt+ and 70,9% of HPV+/Cyt-
cell carcinoma, which can be resolved by morphologic considerations. women (p<0,05) underwent HPV clearance within 3 years and none of
them had either cytological HSIL or a CIN2+ lesion. Cumulative risk for
CIN2+ was 79,3% in the HPV+/Cyt+ group and 43,5% in HPV+/Cyt-
OFP-03-004 women (p<0,05).
The value of fine needle aspiration cytology in the examination of Conclusion: The cumulative risk for developing a CIN2+ lesion 3 years
parathyroid lesions; role of immunocytochemistry and washout fluid after a positive HPV test with mRNA is much higher in women with
analysis abnormal cytology at baseline (79,3% vs 43,5%). The rate of HPV clear-
E. Bakuła-Zalewska1, J. Długosińska2, O. Stanowska3, P. Goralski2, J. ance is lower than the one observed in HPV-positive/Cytology-negative
Gałczyński2 women. Although cytology does not increase the sensitivity of mRNA
1
Department of Pathology and Laboratory Diagnostics, Maria HPV for CIN2+, its impact in the positive predictive value of a positive
Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland, 2 cotest and in patient management is noteworthy.
Department of Oncological Endocrinology and Nuclear Medicine Maria
Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland, 3 Maria
Sklodowska-Curie Institute - Oncology Center, Department of Pathology OFP-03-006
and Laboratory Medicine, Poland BRAF mutation prediction from metastatic melanoma cytological
smear using deep learning: an ongoing project
Background & Objectives: To discerning parathyroid from thyroid in L. Nicolè1, S. Suweis2, R. Cappellesso1, A. Fassina3
1
fine needle aspiration (FNA) smears is difficult. The majority FNA of University of Padua, Italy, 2 Physics and Astronomy Department,
parathyroid lesions is unintended, as intrathyroidal parathyroid adenomas University of Padua, Italy, 3 Department of Medicine, Surgical
and cysts are often mistaken for thyroid lesions. However, the US-guided Pathology & Cytopathology Unit, University of Padua, Italy
FNA for examination of parathyroid has been recently increasingly used
to distinguish abnormal parathyroid glands from lymph nodes, to localize Background & Objectives: Visual inspection of cytological smears is one
atypical or intrathyroidal parathyroid glands and parathyroid lesions in of the main methods used to assess suspicious nodes or mass during follow
recurrent disease. up of patients with malignant melanoma (MM). If metastatic MM (mMM) is
Methods: Seventy-three patients underwent parathyroid FNA either unin- detected, analysis for BRAF mutational status is mandatory in order to
tended during the sampling of suspicious thyroid nodules (35 patients) or identify those cases that are suitable for targeted-therapy. Image analysis
performed specifically to localize parathyroid lesions (38 patients). In ad- based on convolutional neural networks (CNN) showed encouraging results
dition to the examination of smears, measurement of parathyroid hormone in tissue classification and mutation predictions suggesting that deep-
in the needle washouts (FNA-PTH testing) was performed in all patients learning models can be effective ancillary tools to improve the diagnosis.
and immunocytochemical examination (IC) on 15 FNA specimens. Methods: In this study, we started to explore different architectures and
Results: All of the examined FNA samples were correctly diagnosed as components of deep CNNs (https://arxiv.org/pdf/1512.07108.pdf) and
parathyroid lesions in the examination of FNA smears completed by test their accuracy in recognizing BRAF mutational status from digital
FNA-PTH testing and/or IC. Overall organoid and cribriform or trabecu- scanned May-Grunwald-Giemsa stained smears.
lar architecture of three-dimensional and frequently crowded clusters with We have collected 50 stained smears of 30 cases of BRAF-mutated and
overlap of cells and occasional loose clusters with acinar-follicular and/or 20 cases of BRAF-wild type mMM (magnification 200x of 1000*1000
papillary formations were seen in all FNA smears. Cells with small, dark pixel each). From these smears we have extracted patches of around
nuclei with stippled chromatin, and clean or bloody, colloid-free back- 30*30 pixels from each single image, thus creating an overall database
ground was another signs suggestive of parathyroid origin. of 55000 cases. We have used 2/3 of these cases to train the different types
Conclusion: The architectural pattern in the FNA smears helps to distin- of CNNs and the reaming 1/3 as test set.
guish between parathyroid and thyroid aspirates. FNA-PTH testing is a Results: To date, trained algorithm has not achieved satisfactory accuracy
very useful adjunct to determine whether the specimen obtain by FNA (overall accuracy about 60%) in BRAF status prediction.
represents parathyroid or thyroid lesions. IC on FNA specimen is yet Conclusion: Preliminary results highlighted a great dependence of clas-
another technique which increases the diagnostic accuracy. sifier algorithm from input data to achieve a satisfactory level of learning
after training. To fill this gap we are enlarging the case series selecting
additional cases to training the classifier algorithm.
OFP-03-005
The value of an abnormal cytology result in a cervical screening OFP-03-007
cotest study with E6/E7 mRNA. Increased risk for CIN2+ after a 3- Metabonomics profiling of malignant peritoneal effusion with 1H-
year follow-up NMR spectroscopy
R. Granados1, M. Gil1, A. Gutierrez-Pecharromán1, J. Duarte1, A. Villar1, L. Nicolè1, L. Zennaro2,3, P. Vanzani2,3, A. Fassina1
I. Solis1, J.A. Aramburu1, J.M. Rodríguez-Barbero1, P. Bajo1, T. 1
University of Padua, Italy, 2 Department of Molecular Medicine,
Corrales1, E. Camarmo1 University of Padua, Italy, 3 Consortium INBB, Section of Padua,
1
Hospital Universitario de Getafe, Spain Rome, Italy
Virchows Arch

Background & Objectives: Metabonomic profiling of human malignan- Conclusion: In conclusion, delimitation, encapsulation and echogenicity
cies remain a field poorly investigated. Effusion is an optimal of a thyroid nodule as evaluated by US appear to be correlated with the
biospecimens suitable for metabonomic investigation. With this study final histological diagnosis. These results hint that US data may be used to
we addressed a preliminary metabonomic profiling of malignant Ascitic complement the cytological diagnosis, enhancing clinical follow-up.
Effusion (mAE) from patients with Ovarian cancer (OC), Hepatocellular
carcinoma (HCC), and benign Ascitic Effusions (bAE) from patients with
non neoplastic diseases. OFP-03-009
Methods: We have collected 49 samples comprising 20 mAE from OC, 9 Correlation between the ultrasound-guided thyroid fine-needle aspi-
mAE from HCC and 20 bAE. Storage of the samples has been done ration cytology with molecular testing and surgical histopathology
according to a protocol described in our previous study (Zennaro et al. results
2018), and profiling was carried out with 1H-NMR spectroscopy. After H. Seneldir1, G. Kir1, T. Soylemez1, R.B. Girgin1, N. Ozbay1, F. Ozen2,
spectra acquisition principal component analysis was applied to classify H. Ankaralı3, G. Bas4, O. Alimoglu4
1
the effusions Istanbul Medeniyet University, Department of Pathology, Turkey,
2
Results: Our preliminary data suggest how metabonomic profiling could Istanbul Medeniyet University Molecular Biology and Genetics
be effective to classify effusions. In particular, 1H-NMR spectroscopy Department, Turkey, 3 İstanbul Medeniyet University Biostatistics and
could be useful in effusions with low cellularity or in cases where mor- Medical Informatics Department, Turkey, 4 Istanbul Medeniyet
phology or other classical ancillary tests failed to achieve a diagnosis. University, Department of General Surgery, Turkey
From the multivariate statistical analysis (PCA and PLS-DA) performed
on the 1H-NMR spectra recorded, the differentiation of the metabolic Background & Objectives: Molecular testing has been proposed to
profiles between mAE and bAE in OC results to be clear, and mainly refine the assessment of cancer risk in thyroid nodules with indeterminate
due to triglycerides, beta-hydroxybutyrate (BHB), acetate, acetoacetate, cytology. The aim of this study is to compare the genotypic alterations for
lactate, pyruvate and glucose. In particular, all the mentioned metabolites BRAF, NRAS, and KRAS mutations of FNA samples in indeterminate
increase in mAE, while glucose decreases. Conversely, in mAE from and malignant category with subsequent histology of surgical specimens
HCC the metabolites responsible for the difference in the metabolic pro- in our routine practices.
files seem to be different from the ones found as important in OC. Methods: We reviewed 150 cases diagnosed as atypical by ultrasound-
Conclusion: Globally our preliminary data suggest the feasibility of 1H- guided thyroid FNA cytology on the basis of the Bethesda system who
NMR spectroscopy as diagnostic tool in particular in such cases with poor had undergone molecular testing. FNA samples were tested for BRAF,
cellularity. However, due to the few mAE samples collected till now from NRAS, and KRAS point mutations by real-time polymerase chain reac-
HCC, such preliminary results must be confirmed with additional cases. tion (RT-PCR). Out of these 150 cases, 71 had undergone surgical pro-
cedure and histopathology results, were compared with both cytology and
molecular status. According to the final pathological results, we divided
OFP-03-008 the cases, as benign and malign groups.
Ultrasound data may be used to stratify the risk of malignancy of Results: According to the Bethesda System the 71 cases were distributed as
thyroid nodules classified as follicular neoplasm on fine needle aspi- 13 AUS/FLUS, 24 FN/SFN, 13 SM, and 21 malign categories. Of the 71
ration cytology: a retrospective study of 109 cases cases of atypical cytology, 48 cases (67.6 %) were diagnosed as malignant,
D. Pinto1, C. Martins2, D. Felizardo Montezuma3, S. Canberk4,5, F. and 23 cases (32.4 %) were diagnosed as benign at surgical specimens. In
Schmitt4,5 71 nodules, 37 samples (52.1%) had point mutations. Overall positive
1
Centro Hospitalar de Lisboa Ocidental, EPE, Portugal, 2 Escola de predictive value of cytology evaluation was 67.6 % and overall positive
Medicina da Universidade do Minho, Portugal, 3 Instituto Português de predictive value of cytology and molecular testing was 89.2 % (p=0.004).
Oncologia de Coimbra, Portugal, 4 IPATIMUP, Portugal, 5 Faculdade de Conclusion: The addition of molecular testing to FNA cytology may
Medicina da Universidade do Porto, Portugal increase the positive predictive value of cytology.

Background & Objectives: The reported risk of malignancy for thyroid

nodules classified as Follicular Neoplasm/Suspicious for Follicular OFP-03-010
Neoplasm (FN/SFN) on fine needle aspiration (FNA) cytology is be- The accuracy of p16/Ki67 dual staining and HPV DNA test in the
tween 15 and 30%. Diagnostic lobectomy usually follows. Therefore, detection of CIN2+ in women with HSIL cytology: preliminary find-
many unnecessarily surgeries are performed. We wondered if ultrasound ings from a Canadian study
(US) characteristics could be used to further stratify the risk of these R. Alaghehbandan1, S. Ratnam2, L. Gilbert2, D. Jang3, M. Schell3, R.
nodules. Needle2, A. Wadhawan3, D. Costescu3, G. Zahariadis2, M. Chernesky3
1
Methods: FNAs of the thyroid performed at our institution between 2015 Department of Pathology, Faculty of Medicine, University of British
and 2017, with a diagnosis of FN/SFN, were selected. Histology, cytol- Columbia, Royal Columbian Hospital, Vancouver, Canada, 2 Public
ogy and US images were reviewed. Histological diagnoses were divided Health and Microbiology Laboratory, Eastern Health, Canada,
3
into three categories: non-neoplastic, adenoma/NIFTP and malignant. US McMaster University, Canada
images were evaluated regarding delimitation, encapsulation and
echogenicity. A compound score of these variables was developed. Background & Objectives: An ongoing Canadian study is assessing the
Results: 109 cases were included. Histologically, 37 (33.9%) were clas- clinical efficacy of the CINtec PLUS assay (Roche) for triaging women
sified as non-neoplastic, 25 (22.9%) as adenoma/NIFTP and 47 (43.1%) with low-grade squamous intraepithelial lesion (LSIL). As part of this
as malignant. On US, 81 (74.3%) were well-circumscribed, 61 (56.0%) study, we compared the accuracies of CINtec PLUS assay and HPV
encapsulated and 74 (67.9%) isoechoic. Poor circumscription and ab- DNA test (cobas 4800, Roche) to identify high-grade cervical
sence of a capsule were associated with a lower prevalence of adenoma/ intraepithelial neoplasia or worse (CIN2+) in women with LSIL cytology.
NIFTP and a higher prevalence of carcinoma (p=0.0266 and p=0.0147, Methods: LSIL cases seen at the colposcopy clinic, Juravinski Hospital,
respectively). Non-isoechoic nodules were associated with a lower prev- Hamilton were prospectively enrolled with informed consent. Cervical
alence of adenoma/NIFTP (p=0.0266). The compound score was able to specimens were collected at enrolment in ThinPrep for routine Pap. The
stratify nodules between high and low-risk groups, practically excluding remnant from the ThinPrep vials was used for CINtec PLUS immuno-
adenomas/NIFTPs from the high-risk group, which also showed a higher staining to detect biomarkers p16/ki-67 and HPV testing. Biopsy con-
prevalence of carcinoma (p=0.0202). firmed CIN2+ served as the clinical endpoint.
 Virchows Arch

Results: There were 196 (54.3%) patients testing positive for p16/ki-67, underwent surgery. Results of repeated FNA and histology were
and 197 (54.6%)testing positive for HPV with 47 testing positive for evaluated.
HPV genotypes 16/18, and 150 for 12 other HR-HPV. The sensitivity Results: Study of 112 patients with AUS/FLUS who underwent sur-
and specificity of p16/Ki-67 in detecting CIN2+ were 94.6% and 50%, gery: 92 women, 20 men; aged 17-83 years; nodule of median size
respectively. Superior performance was observed for p16/Ki-67 dual 23,5 mm (10-62 mm). After the first AUS/FLUS FNA, 40 patients
staining for detecting CIN2+ with an area under the ROC curve of underwent surgery immediately: 33 (82,5%) were benign nodules
0.723 (p<0.001) compared to 0.277 for HPV testing. (colloid goiter, follicular adenomas, Hurthle cell adenomas, thyroid-
Conclusion: Both p16/Ki-67 dual staining and HPV testing showed sim- itis), 7 (17,5%) were malignant/with malignant potential (papillary
ilar performance in detecting CIN2+ lesions among women with LSIL. carcinomas, noninvasive follicular neoplasm with papillary-like nu-
However a significantly better performance was observed with p16/Ki-67 clear features [NIFTP], well differentiated tumour of uncertain ma-
dual staining. lignant potential). FNA was repeated in 72 cases: 4 (5,6%) unsatis-
factory/non-diagnostic, 4 (5,6%) benign, 4 (5,6%) follicular neo-
plasm, 2 (2,8%) suspicious for malignancy, 4 (5,6%) malignant, 54
OFP-03-011 (75%) AUS/FLUS. Of these repeated AUS/FLUS FNAs, the surgical
Contribution of TERT promoter mutation status to preoperative pathology diagnosis was benign in 47 (87%) (colloid goiters, follic-
diagnosis of thyroid carcinoma ular adenomas, Hurthle cell adenomas) and malignant/with malignant
M. Bella-Cueto1, R. Carrera1, M.d.C. Ramos1, M. Rodriguez1, J.A. potential in 7 (13%) (papillary carcinomas, papillary
Vazquez1, R. Onieva2, I. Capel1, C.M. Blazquez1, F.J. Andreu1, M. microcarcinoma, NIFTP). Overall, 91 (81,3%) of the nodules were
Escoda1, M. Prenafeta1, S. Barcons1, V. Perez1, A. Cano-Palomares1, benign and 21 (18,75%) were malignant or had malignant potential.
F.X. Guirao1, L. Nebot1, E. Gallardo1, M. Rigla1, N. Combalia1 Conclusion: Our results are in concordance with the risk of malignancy
1
Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc predicted by the Bethesda classification for AUS/FLUS. AUS/FLUS
Taulí. Universitat Autònoma de Barcelona, Spain, 2 Universitat FNAs should be repeated since this may change the initial diagnosis
Autònoma de Barcelona, Spain and the therapeutic approach.

Background & Objectives: Thyroid nodules are common among popula-

tion, but barely 4% corresponds to malignant neoplasms. Ultrasound-guided Monday, 9 September 2019 08:30 - 12:00, Galliéni 4
fine needle aspiration biopsy (FNAB) is a worldwide used tool to guide the OFP-04 | Breast Pathology
patients’ management, but in some entities the main diagnostic criteria of
malignancy must be evaluated in the surgical specimen. C228T mutation of
telomerase reverse transcriptase promoter (TERTp) has been identified as OFP-04-001
specific of malignancy, but its detection by pyrosequencing has been slightly Hormone- and HER2-receptor assessment in 33,046 breast cancer
reported. The aim of our study is to determine the incidence of C228T patients: a nationwide comparison of positivity rates between pathol-
TERTp mutation by pyrosequencing in thyroid nodules classified by ogy laboratories in the Netherlands
FNAB as consistent with follicular neoplasm, and to establish the profitabil- C. van Dooijeweert1, I. Deckers2, I. Baas3, E. van der Wall3, P. van Diest4
1
ity of its detection in the corresponding FNAB material. Department of Pathology, University Medical Center Utrecht,
Methods: Inclusion criteria: Patients with thyroid nodules classified by The Netherlands, 2 PALGA Foundation (the nationwide network and
FNAB as consistent with follicular neoplasm and followed by thyroidec- registry of histo- and cytopathology in The Netherlands), Houten,
tomy between 1993 and 2015. Methods: cases were retrieved from the The Netherlands, 3 Department of Medical Oncology, University
Pathology Department archives. Demographics, clinical data, and cyto- Medical Center Utrecht, The Netherlands, 4 University Medical Center
logical and histological diagnoses were recorded. Selected material from Utrecht, The Netherlands
paraffin blocks was processed by pyrosequencing to detect C228T
TERTp mutation. In mutated cases, FNAB material was also studied. Background & Objectives: Patient management of invasive breast can-
Results: 62 cases fulfilled the inclusion criteria. C228T TERTp mutation cer (IBC) is to a large extent based on hormone- and HER2-receptor
was detected in 9 tumours (14,5%), and in the corresponding FNAB assessment. High-quality, reliable receptor assessment is of key-
material of 7 of them - the ones with enough material to perform the importance as false results may lead to under- or overtreatment of pa-
study-. In 4/9 cases a delayed completion thyroidectomy was needed. tients. Surveillance of case-mix adjusted positivity rates has been sug-
Conclusion: Study of C228T TERTp mutation status by pyrosequencing gested as a tool to identify laboratories with insufficient testing assays, as
can be of help to detect malignant thyroid nodules, eventually indicating this covers the whole process of receptor assessment and enables labora-
total thyroidectomy as the first and definitive surgery, avoiding a second tories to benchmark their positivity rates against other laboratories.
intervention. Methods: We studied laboratory-specific variation in hormone- and
HER2-positivity rates of 33,046 breast cancer patients using real-life
This work was supported by Fundación 2000, Fundació Parc Taulí. nationwide data. All synoptic pathology reports of IBC resection-speci-
mens, obtained between 2013-2016, were retrieved from the nationwide
Dutch Pathology Registry (PALGA). Absolute and case-mix adjusted
OFP-03-012 positivity rates were compared to the mean national proportion and pre-
Thyroid nodules with AUS/FLUS cytology: what happens next? sented in funnel plots in separate analyses for estrogen (ER), progesterone
J. dos Santos1, R. Machado-Neves1, T. Amaro1, M. Honavar2 (PR) and HER2. Case-mix adjustment was performed by multivariable
1
Pathology Department - Hospital Pedro Hispano, Portugal, Portugal, logistic regression.
2
Unidade Local de Saúde de Matosinhos - Portugal, Portugal Results: 33,794 IBC lesions from 33,046 patients of 39 pathology labo-
ratories were included. After case-mix adjustment, mean positivity rates
Background & Objectives: Fine-needle aspiration (FNA) has a significant were 87.2% for ER (range: 80.4-94.3), 71.3% for PR (62.5-77.5%), and
role in assessing the malignancy risk of thyroid nodules. Our aim is to study 9.9% for HER2 (5.5-12.7%). Overall, 14 (35.9%), 17 (43.6%) and 11
thyroid nodules with cytological diagnosis of atypia of undetermined (28.2%) laboratories showed positivity rates outside the 95% confidence
significance/follicular lesion of undetermined significance (AUS/FLUS). interval for ER, PR and HER2 respectively.
Methods: Retrospective study of 3186 thyroid FNAs between January Conclusion: This nationwide study shows that absolute variation in
2014/December 2018. 334 (10,5%) classified as AUS/FLUS; 112 hormone- and HER2-receptor positivity rates between Dutch pathology
Virchows Arch

laboratories is limited. Yet, the considerable number of outlying labora- Methods: A total of 2385 haematoxylin and eosin stained tissue slides of
tories shows that there is still need for improvement. Continuous moni- primary breast cancer patients from 1809 patients were assessed for TSR
toring and benchmarking of positivity rates may help to realize this. via a digital application for the evaluation of microscopic images. A
percentage of less than or equal to 50% stroma was categorized as
Funding by: The Quality Foundation of the Dutch Association of Medical stroma-low and more than 50% stroma was categorized as stroma-high.
Specialists (SKMS) Results: TSR showed to be an independent prognostic parameter for both
RFP (HR 1.34, 95% CI 1.09-1.65, p = 0.005) and BCSS (HR 1.52, 95%
CI 1.17-1.96, p = 0.001). The prognostic effect of the TSR was highest in
OFP-04-002 grade III tumours. Stroma-low/grade III tumours had a statistically sig-
Significant inter- and intra-laboratory variation in grading of inva- nificant better prognosis compared to stroma-high/grade III tumours
sive breast cancer: a nationwide study of 33,043 patients in the (BCSS: HR 1.87, 95% CI 1.35-2.59, p < 0.001 and RFP: HR 1.82,
Netherlands 95% CI 1.33-2.50, p < 0.001).
C. van Dooijeweert1, P. van Diest2, S. Willems1, C. Kuijpers1, E. van der Conclusion: The prognostic effect of the TSR validates in most sub-
Wall3, L. Overbeek4, I. Deckers4 groups. In this study, the prognostic effect of the TSR is highest in grade
1
Department of Pathology, University Medical Center Utrecht, III tumours. TSR could contribute to clinical decision making for breast
The Netherlands, 2 University Medical Center Utrecht, The cancer therapy.
Netherlands, 3 Department of Medical Oncology, University Medical
Center Utrecht, The Netherlands, 4 PALGA, the nationwide network
and registry of histo- and cytopathology in the Netherlands, Houten, OFP-04-004
The Netherlands High Pregnane-X-Receptor (PXR) expression is correlated with poor
prognosis in invasive breast carcinoma
Background & Objectives: Accurate, consistent, and reproducible grad- D. Pouloudi1, C. Giaginis2, S. Gourzi1, P. Alexandrou1, G. Tsourouflis3,
ing by pathologists is of key-importance for identification of individual A. Michail4, N. Tsoukalas1, S. Albesher1, P. Politis4, L. Nakopoulou1, S.
patients with invasive breast cancer (IBC) that will or will not benefit Theocharis1
1
from adjuvant systemic treatment. We studied the laboratory-specific First Department of Pathology, Medical School, National and
grading variation using nationwide real-life data to create insight and Kapodistrian University of Athens, Greece, 2 Department of Food
awareness in grading variation. Science and Nutrition, University of the Aegean, Myrina, Lemnos,
Methods: Synoptic pathology reports of all IBC resection-specimens, Greece, 3 2nd Department of Propedeutic Surgery, School of Medicine,
obtained between 2013-2016, were retrieved from the nationwide National and Kapodistrian University of Athens, Greece, 4 Section of
Dutch Pathology Registry (PALGA). Absolute differences in Molecular Biology, Biomedical Research Foundation, Academy of
laboratory-proportions of grade I-III were compared to the national ref- Athens, Greece
erence. Multivariable logistic regression provided laboratory-specific
odds ratios (ORs) for high- versus low-grade IBC. Background & Objectives: Pregnane X Receptor (PXR) is involved in
Results: 33,792 IBC pathology reports of 33,043 patients from 39 human malignancy, either by directly affecting carcinogenesis or by in-
laboratories were included, of which 28.1% were reported as grade I ducing drug-drug interactions and chemotherapy resistance. The clinical
(range between laboratories 16.3-43.3%), 47.6% as grade II (38.4- significance of PXR expression in invasive breast carcinoma was evalu-
57.8%), and 24.3% as grade III (15.5-34.3%). Based on national ated in our study.
guidelines, the indication for adjuvant chemotherapy was dependent Methods: PXR protein expression was assessed immunohistochemically
on histologic grade in 29.9% of patients. After case-mix correction, on formalin fixed paraffin-embedded breast invasive carcinoma tissue
20 laboratories (51.3%) showed a significantly deviant OR. sections obtained from 148 patients and was correlated with clinicopath-
Significant grading differences were also observed among patholo- ological parameters, molecular phenotypes, tumour cells’ proliferative
gists within laboratories. capacity and overall and disease-free patients’ survival. Additionally,
Conclusion: In this cohort of 33,043 breast cancer patients we observed the expression of PXR was examined on human breast carcinoma cell
substantial inter- and intra-laboratory variation in histologic grading. It lines of different histological grade, hormonal status and metastatic po-
can be anticipated that this has influenced outcome including exposure to tential (MDA-MB231, MDA-MB468, MDA-MB453, MCF-7, T47D).
unnecessary toxicity, since choice of adjuvant chemotherapy was depen- Results: PXR positivity was noted in 79 (53.4%) and high PXR expres-
dent on grade in nearly a third of patients. Better standardization and sion in 48 (32.4%), out of 148 breast carcinoma cases. High PXR expres-
training seems warranted. sion was positively associated with nuclear grade (p=0.0112) and histo-
logical grade of differentiation (p=0.0305), as well as with tumour cells’
Funding by: The Quality Foundation of the Dutch Association of Medical proliferative rate (p=0.0051), and negatively with luminal-A subtype
Specialists (SKMS) (p=0.0295). Associations between high PXR expression and estrogen
and progesterone receptor negative status were also recorded (p=0.0314
and p=0.0208, respectively). High PXR expression was associated with
OFP-04-003 shorter overall patients’ survival times (p=0.0009). In multivariate analy-
The prognostic value of the tumour-stroma ratio validates in sub- sis, high PXR expression was identified as an independent prognostic
groups of breast cancer, especially in grade III tumours factor of overall patients’ survival (p=0.0082). PXR expression alterations
W. Mesker1, K. Vangangelt2, A. Green3, I. Heemskerk2, D. Cohen2, H. were also noted in breast cancer cell lines of different hormonal status.
Putter2, E. Rakha3, R. Tollenaar2 Conclusion: The present data supported evidence that PXR was highly
1
Leiden University Medical Centre, The Netherlands, 3 University of expressed in invasive breast carcinoma and related with a more aggres-
Nottingham, United Kingdom sive phenotype, being also a strong and independent poor prognosticator.
Background & Objectives: The tumour-stroma ratio (TSR) is a prom-
ising prognostic parameter based on tumour-associated stroma within the
primary tumour. The heterogeneous cancer types of breast cancer with OFP-04-005
various histological subtypes complicate clinical decision making. This The immune microenvironment in young patients with triple nega-
large validation study aims at the prognostic implication of TSR in the tive breast cancer
various subgroups of breast cancer in a digital pathology environment. H. McKenzie1,2, G. Martland3, D. Eccles1, E. Copson1,2, G. Thomas1,2
 Virchows Arch

1
University of Southampton, United Kingdom, 2 University Hospital Conclusion: These data point out the HMTV specificity of the gene panel
Southampton NHS Foundation Trust, United Kingdom, 3 Poole selected and its possible use as a screening tool or classifier in BC.
Hospital NHS Foundation Trust, United Kingdom

Background & Objectives: Triple negative breast cancers (TNBC) com- OFP-04-007
prise 15-20% of breast cancers and are associated with adverse outcomes; Correlation of the results of Ki67 in intrinsic subtypes of invasive
the prognosis for younger women is worse. Tumour-infiltrating lympho- breast carcinomas with the effect of systemic neoadjuvant treatment
cytes (TILs) significantly correlate with improved survival in many can- W.P. Olszewski1, M. Chraszczewska2, J. Plisiecka1
1
cers. Conversely, tumoural expression of programmed death ligand 1 Department of Pathology, Center of Oncology, Warsaw, Poland, 2 Maria
(PD-L1) is associated with T-cell exhaustion and is commonly a negative Sklodowska-Curie Institute - Oncology Center, Department of Pathology
prognostic marker. Mechanisms suppressing the immune response in and Laboratory Medicine, Poland
TNBC remain unclear.
Methods: We evaluated immunological markers in a prospective cohort of Background & Objectives: The study used 78 breast cancer cases qual-
young patients (<41 yrs) with TNBC (POSH; n=350). We evaluated stro- ified for neoadjuvant treatment. In the evaluated group, there were 28
mal TILs, cancer-associated fibroblasts (smooth muscle actin; SMA), CD8 cases of triple-negative (ductal) carcinomas, 25 cases of HER2 positive
(effector T-cells) and PD-L1 (on tumour cells). Survival analyses were (non-luminal) carcinomas, 8 cases of Luminal B (HER2 positive) carci-
summarised with Kaplan-Meier curves (log-rank test). Multivariable Cox nomas and 17 cases of luminal B (HER2 negative) carcinomas. Clinically
regression analysis and variable correlation analyses were also performed. all tumours were in Stage III.
Results: TILs were significantly associated with good prognosis; relative Methods: In order to more accurate measurements than the routine Ki67
to low TILs (<20%), the hazard ratio for overall survival for those with evaluation, Ki67 was reassessed in the CB material. Ki67 was evaluated
high TILs (>60%) was 0.106 (0.015-0.762; p=0.026). Relative to low in 500 cells. Three pathologists carried out an independent assessment of
PD-L1 expression, the hazard ratio for those with high expression was Ki67. Residual Cancer Burden value, percentage of pCR and the decrease
0.374 (0.207-0.675; p=0.001). TILs negatively correlated with expression in cellularity were measured in all post treatment histologic material.
of SMA, r=-0.211 (p=0.001) and positively correlated with expression of Results: It was shown that higher Ki67 index correlates with the degree
PD-L1 (r=0.598, p=1.792-32). of response assessed as the calculated Residual Cancer Burden value,
Conclusion: TILs are significantly prognostic in young women with percentage of pCR and the decrease in cellularity in the subgroups of
TNBC. High PD-L1 expression is also associated with improved triple-negative and HER2 positive (ductal) cancers. In the groups of lu-
survival. Notably, the presence of CAFs in the tumour stroma minal B cancers, such correlation was not found.
inversely correlated with TILs suggesting that these cells may be Conclusion: The Ki67 index predicts the response to neoadjuvant treat-
immunosuppressive. These data suggest that inhibiting CAFs may ment assessed as the calculated Residual Cancer Burden value, percent-
be a strategy to improve clinical response to immunotherapy and age of pCR and the decrease in cellularity in HER2 positive cancer and
we are currently evaluating the efficacy of CAF targeting in murine triple-negative (ductal) subtype.
immunotherapy models.

This work was supported by Cancer Research UK. OFP-04-008

Independent HER2-targeted therapy resistance predictors:
intratumoural heterogeneity in breast carcinoma HER2 gene copy
OFP-04-006 number and protein expression
Utility of a gene expression panel as a screening tool for human H. Nitta1, R. Horii2, R. Maruyama2, M. Nojima3, M. Matsuura2, D.
mammary tumour virus infection in breast cancer Munroe1, P. Banks4, F. Akiyama2
C. Scatena1, P. Civita2, F. Lessi2, P. Aretini2, M. Menicagli2, C. Marchiò3, 1
Roche Tissue Diagnostics, USA, 2 Japanese Foundation for Cancer
C.M. Mazzanti2, G. Bevilacqua1, A.G. Naccarato1 Research, Japan, 3 The University of Tokyo, Japan, 4 University of
1
University of Pisa, Italy, 2 Fondazione Pisana per la Scienza, Italy, North Carolina at Chapel Hill, USA
3
University of Turin, Italy
Background & Objectives: We employed two methods for the detection
Background & Objectives: Etiology of human breast cancer (BC) is of HER2 genetic heterogeneity (GH; a mixture of classic HER2 positive
unknown, with the exception of hereditary tumours. On the other hand, and negative tumour cells) and non-GH (NGH; a mixture of classic HER2
the Mouse Mammary Tumour Virus (MMTV) is recognized as the etio- positive tumour cells and HER2 gene amplified tumour cells without
logical agent of mouse mammary carcinoma. Several data suggest the HER2 protein): 1) visual microscopic HER2-intratumoural heterogeneity
existence of a human equivalent of MMTV (HMTV) such as the presence (ITH) and 2) quantitative HER2-diversity (based on enumeration of large
of viral sequences in human BC or, intriguingly, saliva, offering a possible numbers of individual cells in respect to HER2 gene copy number and
route of infection. However, the identification of HMTV in BC tissue may protein expression levels) in relation to neoadjuvant trastuzumab-based
be inaccurate due to the difficulty in DNA amplification or the loss of the chemotherapy.
virus during progression, as earlier hypothesized. The aim of the present Methods: Archived tissue samples from 102 neoadjuvant trastuzumab-
study was to obtain a gene panel able to determine if a BC is due to the treated HER2-positive breast cancer patients were studied with the HER2
HMTV viral infection regardless of presence of viral sequences. gene-protein assay (a combination of immunohistochemistry and bright-
Methods: The panel was built through a systematic search from biblio- field in situ hybridization). HER2-ITH was microscopically assessed for
graphic datasets. 31 formalin-fixed, paraffin-embedded specimens were HER2 gene (amplified, non-amplified) and protein (positive, negative).
selected to test the panel: 7 HMTV positive BC (pBC), 7 HMTV negative Quantitative analysis was for gene copy number (≥6, 5-4, ≤3) and protein
BC (nBC), 7 hereditary BC (HBC) and 9 specimens of normal breast expression (3+, 2+, 1+, 0) among individual tumour cells. Logistic re-
tissue (NBT) as controls. The experiment was conducted according to gression analyses of the results were compared in relation to pathological
TruSeq Gene Expression Panel (NextSeq500-Illumina). Data were per- complete response (pCR, 49%) and non-pCR (51%).
formed by Principal Component Analysis (PCA). Results: Visual HER2 GH and NGH was detected in 8.8% and 30.4% of
Results: The pBC group was clearly discriminated from the nBC group. the cohort, respectively. Fewer NGH patients achieved pCR compared to
Interestingly, the nBC group co-localized with the HBC group, whereas, homogenous patients (p=0.0189, OR=2.925). Quantitative analysis
the NBT group localized far from all the other groups. showed that patients with higher HER2 gene copies and less protein
Virchows Arch

expression variation achieved pCR more frequently (AUC=0.723). environmental interactions. The existing multiplexing procedures, based
Furthermore, HER2-ITH indicators were strengthened with the diagnos- on iterative cycles, are resource-expensive and impractically long, impeding
tics ability of conventional pathological markers (AUC=0.780 to 0.855, their implementation in daily routine. Here we aimed to develop a fully
sensitivity 76.0%, specificity 84.3% in ROC analysis). automated ultra-fast work-flow for multiplexed immunofluorescence-
Conclusion: Visual microscopy and quantitative HER2-diversity enu- staining employing the tyramide signal amplification (TSA) method by
meration identified ITH as independent resistance factors to neoadjuvant using a microfluidic tissue processor (MTP).
trastuzumab-based chemotherapy. Methods: Formalin-fixed-paraffin-embedded (FFPE) sections of tissue
micro-arrays, containing ten human breast carcinoma and one liver cancer
cases, underwent manual deparaffinization and antigen retrieval. The
OFP-04-009 multiple staining and elution steps were automatically executed on the
Investigation of microRNA expression profiles related to morpholog- microfluidic device without intervention needed. The elution step on the
ical heterogeneity in triple-negative breast cancer MTP was optimised to reach comparable efficiency to the standard elu-
M. Koleckova1, Z. Kolar2, J. Ehrmann1, M. Svoboda3, O. Slaby3, J. tion method performed in a microwave oven. Four markers, namely CK
Bouchal1, K. Bouchalova4, M. Janikova5, J. Srovnal6, L. Radova3 (cytokeratin), ER/PR (estrogen/progesterone receptor) and Her2 (human
1
Department of Clinical and Molecular Pathology, Faculty of Medicine epidermal growth factor receptor 2), were detected by a fluorescent TSA
and Dentistry, Olomouc, Czech Republic, 2 Faculty of Medicine and reaction mediated by the horseradish peroxide (HRP) enzyme conjugated
Dentistry, Palacky University Olomouc, Czech Republic, 3 Central to a secondary antibody.
European Institute of Technology, Masaryk University, Brno, Results: The developed protocol for a single plex lasts in average 15
Czech Republic, 4 Institute of Molecular and Translational Medicine, minutes for the immunostaining and 5 minutes for the antibodies removal.
Faculty of Medicine and Dentistry, Olomouc, Czech Republic, Using the MTP technology, we established a 4-plex automated
5
University Hospital Olomouc, Czech Republic, 6 Institute of multistaining of clinically relevant biomarkers for breast cancer diagnosis
Molecular and Translational Medicine, Faculty of Medicine and within 84 minutes. The performance of the automated steps showed per-
Dentistry, Olomouc, Czech Republic fect agreement with the state-of-the-art.
Conclusion: With a turn-around time shorter than existing monoplex
Background & Objectives: Triple-negative breast cancers (TNBCs) are immunohistochemistry methods, our automated multiplexing technology
morphologically a heterogeneous group of breast carcinomas with no or has the potential to enable multistaining in routine without disturbing the
minimal hormone receptor and HER2 protein expression or gene ampli- current laboratory workflow, opening perspectives for implementation of
fication. Due to its aggressive nature, novel therapeutic targets are urgent- -omics approaches in tissue diagnostics.
ly required to improve pathological complete response and clinical out-
comes. In tumours, microRNAs (miRs) exhibit both oncogenic and
tumour-supressor function. The aim of this study was to indentify a pos- OFP-04-011
sible association between miRs expression profile and intratumoural mor- PD-L1 testing in triple negative breast cancer
phology within different samples of TNBC. F. Dobritoiu1,2, A. Chefani2, K. Billingham3, M. Chenard4, R. Vaziri5, M.
Methods: We analysed the tumour miRs expression in relation to mor- Lacroix-Triki6, A. Waydelich7, G. Erb7, P. Toro8, S. Wedden2,9, C.
phological heterogeneity of 25 TNBC samples of a diameter less than D'Arrigo2
1
2 cm obtained from patients without previous neoadjuvant chemotherapy Emergency University Hospital, Bucharest, Romania, 2 Poundbury
with respect to tumour morphology preservation. We used microdissec- Cancer Institute, Dorchester, United Kingdom, 3 Great Western
tion techniques for the isolation of tumour cells from areas with specific Hospital Swindon, United Kingdom, 4 CHU de Strasbourg,
morphology from paraffin sections, isolation of total RNA, miRs micro- Dèpartement de Pathologie, France, 5 Worcestershire Acute Hospitals,
array analysis to compare tumour morphology with their profile. Department of Pathology, United Kingdom, 6 Gustave Roussy Cancer
Results: The analysed tumours were invasive carcinomas NST with med- Campus, Dèpartement de Pathologie, Villejuif, France, 7 Roche TD,
ullary features, with central fibrosis/necrosis, tendency to spindle cell and/ EMEA LATAM, Roche Diagnostics, France, 8 Roche TD, EMEA
or apocrine metaplastic differentiation and extensive lympho/plasmocytic LATAM, Roche Diagnostics, Spain, 9 CADQASCIC, Dorchester,
infiltration. In morphologically distinct parts of tumours we revealed United Kingdom
seven candidate miRs represented by miR-93-5p, miR-106b-5p, miR-
145-5p, miR-182-5p, miR-200c-3p, miR-205-5p and miR-361-5p which Background & Objectives: Overall survival for triple negative breast
corresponded with areas of the predominantly medullar, spindle cell, clear cancer (TNBC) is low despite good response to chemotherapy; how-
cell, lymphocyte rich, precancerous and normal morphology . ever, recently, FDA approved atezolizumab for advanced TNBC with
Conclusion: We confirmed a possible association of specific miRs ex- SP142 inmmunohistochemistry assay as a Companion Diagnostic
pression with specific morphological pattern in TNBC. Our results indi- (CDx) and EMA and NICE are considering approval. Percentage of
cate miRs relevance for formation different neoplastic and non-neoplastic PD-L1(+) immune cells (IC) is used for patient selection, with thresh-
morphological conditions including lympho/plasmocytic infiltration. old set at 1%. Today, there is no data on TNBC PD-L1 heterogeneity
Additional examinations are needed for distinguishing of primary and/ and the choice of tissue tested may influence patient selection. This
or subsequent role of miRs in these processes. study compares PD-L1 expression in core biopsy (CB) and surgical
excision tissue samples in order to determine which specimen is
Supported by AZV 16-31997A optimal.
Methods: We investigated 73 cases of invasive TNBC with matched CB
and excision samples (up to 5 tissue blocks/case). PD-L1 status was
OFP-04-010 evaluated by IHC with SP142 CDx on Ventana Benchmark using the
Ultra-fast and automated immunohistofluorescent multistaining approved scoring algorithm. All PDL1(+) tumour-associated IC were
using a microfluidic tissue processor quantified as % of tumour area. Tumours were classified as PD-L1(+)
G. Cappi1, D.G. Dupouy1, M.A. Comino1, A.T. Ciftlik1 (≥1%) or PD-L1(-) (<1%). Each slide was scored independently. For each
1
Lunaphore Technologies SA, Switzerland case, a final PD-L1 status was obtained by averaging all excision slides.
Results: 38/73 cases (52%) were PD-L1(+) as final diagnosis. 16/73
Background & Objectives: Simultaneous detection of multiple markers, cases (22%) had PD-L1(-) on core and PD-L1(+) on final diagnosis.
on a single tissue section, allows investigating the complex tumour- 16% had discordant PD-L1 status between excision blocks.
 Virchows Arch

Conclusion: We showed that there are 42% fewer PD-L1 (+) cases when chromosome enumeration prob (CEP˃2,5). The purpose of our study
assessed on CB alone. No PD-L1(+) cases on CB became negative on was to highlight the clinocopathologics significant of chromosome 17
final diagnosis. A PD-L1(-) CB should trigger retesting on excision and, polysomy.
because of the discrepancy amongst blocks from the same excision, if the Methods: This is a retrospective analysis of a large series of 203 cases of
initial block is PD-L1(-), retesting on additional excision blocks should be primary invasive breast carcinomas with equivocal HER2 IHC staining
considered. This will ensure that patients are not denied this therapeutic (IHC HER2 2+) whom her-2 fluorescence in situ results and clinicopath-
option. ological data were available from 2012 to 2018 at the Department of
Pathology of Hassan II University Hospital of Fes, in which we identify
15 cases of chromosome 17 polysomy.
OFP-04-012 Results: As results, among 203 cases of invasive breast carcinoma
Automatic quantification of HER2 amplification in invasive breast analysed by FISH, 20% of the cases showed HER-2 gene amplification.
cancer using chromogenic in situ hybridization (CISH) and compu- A total of 15 (7,5%) cases showed the presence of polysomy 17. Absence
tational pathology of polysomy 17 was seen in the remaining 188 cases. The two groups
M.S. Hossain1,2, T. Nakamura1, M. Hanna2, N. Uraoka2, D. S. Ross2, M. polysomy and non polysomy 17 were classified according to the HER2
R. Hameed2, M. Yamaguchi1, Y. Yagi2 gene amplification status. Among 15 cases, 11 (73,3%) were HER-2 non-
1
Tokyo Institute of Technology, Japan, 2 Memorial Sloan Kettering amplified, 4 (25,7%) were HER-2 amplified. Among 188 non polysomy
Cancer Center, USA cases, 152 (80%) were HER-2 non amplified, 36 (20%) were HER-2
amplified. Polysomy 17 showed a significant association with poor path-
Background & Objectives: HER2 gene amplification has prognostic ological parameters including low age (under 50ans p=0,06), low mitotic
and therapeutic indications in breast cancer. Fluorescent in situ hybridi- score (p=0,05), high nuclear ploemorphism score (p=0,03) high histolog-
zation (FISH) and CISH are the standard assays to determine the ampli- ical grade (p=0,03), presence of node metastasis (p=0,04), not otherwise
fication status. CISH is evaluated by counting at least 20 cancer nuclei specified histological type (p=0,009). Showed more often in positive
manually, according to the American Society of Clinical Oncology hormone receptors status and high KI-67 proliferation index. Similarly,
(ASCO)/College of American Pathologists (CAP) guidelines. However, in HER-2 non amplified gene, polysomy 17 showed an association with
this process is time prohibitive. We propose a system to quantify the almost the same aggressive histological variable.
HER2 amplification status automatically from CISH whole slide images Conclusion: In our study, we identified 7,35% cases of polysomy 17. We
(WSI) using computational pathology revealed that the polysomy 17 can serve as a poor prognostic marker in
Methods: Breast pathologists annotated tumour regions from CISH WSI invasive breast cancer. We also highlight the prognostic value of
at 40x (0.13 um/pixel). We detected singular nuclei using machine learn- polysomy 17 in luminalB/HER-2 negative.
ing from annotations, then HER2 and CEP17 signals based on RGB
intensity. Our model mirrors the ASCO/CAP guidelines. We assessed
nuclei where CEP17≥2 and HER2>CEP17, then quantified 20 nuclei OFP-04-014
with highest (HER2-CEP17) differentiation values. Finally, the HER2 The impact of standardised structured reporting of pathology re-
status was determined as amplified if HER2/CEP17 ratio≥2.0 or non- ports for breast cancer in the Netherlands
amplified if <2.0. Additionally, another 20 nuclei were quantified if the A. Snoek1, N. Hugen1, L. Overbeek2, I. Nagtegaal1
ratio was ≥1.8 and ≤2.2 1
Department of Pathology, Radboud University Medical Centre,
Results: We randomly selected 13 patient specimens that were diagnosed Nijmegen, The Netherlands, 2 PALGA, the nationwide network and reg-
with invasive breast carcinoma with prior immunohistochemistry and istry of histo- and cytopathology in the Netherlands, Houten,
FISH. Then quantified the 13 cases using the proposed method which The Netherlands
included 9 positive and 4 negative cases. Results of the proposed auto-
matic quantification were compared with pathologists manual CISH Background & Objectives: With the increasing complexity of modern
counting. The correlation coefficient between the manual and automatic oncological patient management and the growing amount of information
CISH ratio was 0.97 which indicates the efficacy for the proposed method needed from the pathologist, traditional narrative reports (NRs) do not
Conclusion: The proposed method has a high concordance with manual suffice. Both completeness and readability are shown to increase with
quantification. In the future, invasive cancer regions will be detected standardised synoptic reporting (SSR). In the Netherlands SSR for breast
using deep learning and the final system will enable automatic annotation cancer was introduced in 2009. We explored the impact of this introduc-
of cancer regions followed by the automatic quantification tion on completeness of reporting, individual patient treatment and
outcome.
Methods: Using the Netherlands Cancer Registry and national pathology
OFP-04-013 archive , a retrospective, population based cohort study was conducted.
CEP17 copy number gain: correlation of 15 cases with clinicopatho- Data of breast cancer resections from 2007-2014 were collected to com-
logical parameters and HER-2 gene amlification. Experience from a pare NR and SSR for all outcome measures.
single institute Results: 76,796 cases were included of which 26,671 (34.7%) reports
S. Gamrani1, A. Douida1, A. Mazti1, F. El Agy1,2, B. Efared1, H. El were SSR. Overall completeness was higher for SR than for NR (93.6%
Fatemi1,3 versus 90.1%). SR were significantly more complete for most individual
1
Department of Pathology, Hassan II University Hospital, Fez, Morocco, parameters, except for histological type, pT and lymph node count, where
2
Faculty of Medicine and Pharma, Molecular Biology, Fez, Morocco, SR and NR were equal. Of the HER2-positive patients with SR, 69.2%
3
Faculty of Medicine and Pharmacy of Fez, Morocco received anti-HER2 targeted therapy compared to 58.7% HER2-postive
patients with NR. Patients with an incomplete pathology report had a
Background & Objectives: As Anti-Her-2 containing therapy has be- higher crude probability of death, which remained significant for patients
come an important treatment for Her-2 positive breast cancer. The ratio of with a NR after adjustment for patient and tumour characteristics (HR:
human epidermal growth factor receptor 2 (HER2) to CEP17 by fluores- 1.24 (95%CI 1.03-1.51)).
cent in situ hybridization (FISH) with the centromeric probe CEP17 is Conclusion: In this large nationwide cohort of breast cancer resections,
evaluated to determine HER2 gene status as a standardised method. But we demonstrate that SR are more complete than NR. More complete
during the interpretation of FISH, the result may be critical in tumours pathology reports are expected to improve communication between spe-
with chromosome 17 polysomy defined as increased copy number of cialists regarding parameters important for adjuvant breast cancer
Virchows Arch

treatment decisions, subsequently improving breast cancer care and pa- Methods: PDAC-tissue from long-term- (LTS, n=30, overall survival
tient outcomes. (OS) >60 months); mid-term- (MTS, n=30, OS:12-60 months) and
short-term survivors (STS, n=40, OS:3-12 months) was analysed by im-
munohistochemistry on tissue microarrays for immune cell populations
OFP-04-015 and signaling molecules. Intratumoural cytokine-profiles were assessed
Correlation between primary tumour and axillary lymph node re- by mRNA in situ hybridization. Further, we performed next generation
sponse to neoadjuvant chemotherapy in breast cancer patients sequencing for “hotspot” mutations in oncogenes and tumour suppressor
G. Kir1, Z.C. Olgun1, I.N. Okten2, H. Ankarali3, R.B. Girgin1, M.K. genes. Clinicopathologic features, including tumour budding were
Melemez4, O. Alimoglu5 integrated.
1
Istanbul Medeniyet University, Department of Pathology, Turkey, Results: LTSs exhibit low mutational frequency in the main genetic
2
Istanbul Medeniyet University, Department of Oncology, Turkey, drivers CDKN2Aand SMAD4, a T lymphocyte enriched microenviron-
3
Istanbul Medeniyet University, Department of Statistics, Turkey, ment including an expanded number of CD4+T cells, a Th1 tilted cyto-
4
Istanbul Medeniyet University, Turkey, 5 Istanbul Medeniyet kine-profile, high MHC class I along with low pSTAT3 levels and low-
University, Department of General Surgery, Turkey grade tumour budding. Conversely, STSs display a high mutational fre-
quency in all known PDAC key genetic drivers (KRAS, TP53,
Background & Objectives: There can be inconsistencies between pri- CDKN2Aand SMAD4) and an immunosuppressive microenvironment
mary tumour and axillary lymph node response to neoadjuvant chemo- rich inTregs and M2-polarized macrophages with fewer effector T cells.
therapy (NAC) in breast cancer patients. The aim of this study is to They also display a Th2 skewed cytokine-profile, low MHC class I along
evaluate this correlation. with high pSTAT3 levels and high-grade tumour budding. Finally, MTSs
Methods: A retrospective study was carried out in 114 node- exhibit high mutational frequency in non-key driver genes and immune–
positive breast cancer patients, who had axillary dissection, from rich tumours but a largely Th2 skewed cytokine-signature.
2 centers between 2009-2019 who treated with NAC before surgery. Conclusion: Within each PDAC-subgroup different mechanisms shift
Tumour response was evaluated pathologically as complete the balance between tumour-intrinsic signaling and anti-tumour immune
response(CR)/partial response(PR)/without response(WR) by using activity with impact on morphology and clinical features of these tu-
Sataloff et. all, 1995 for primary tumour and axilla seperately. mours.
Results: Seventy-eight patients (69%) had statistically significant
consistency between NAC responses of primary tumour and This work was funded by the Foundation for Clinical-Experimental
axilla(p:0,0001, kappa coefficent: 0.509). We had one patient with Tumour Research.
major inconsistency between NAC responses (CR at primary tu-
mour and WR at axilla). After 19 months follow up she was de-
void of disease. Multivariate cox regression analysis revealed that OFP-05-002
CR and PR were independent predictors of disease free A gene expression signature of microvascular invasion in hepatocel-
survival(DFS). (Primary tumour CR - CI:0.007-0.402, p:0.005; lular carcinoma in formalin fixed-paraffin embedded biopisies
Primary tumour PR – CI:0.059-0.352, p: 0.000; Axilla CR - A. Beaufrère1,2, S. Caruso3, G. Couchy3, J. Zucman-Rossi4, N. Potè5,6, V.
CI:0.012-0.654 p:0.018; Axilla PR - CI:0.073-0.529 p:0.001). Paradis1,2
1
There were no significant differences between CR and PR for both Pathology Department, Beaujon University Hospital, AP-HP, Clichy,
primary tumour and axilla regarding DFS (CI:0.342-21.893, France, 2 INSERM U1149, Beaujon University Hospital, Clichy, France,
3
p:0.343; CI:0.263-19.315, p:0.458 respectively). Due to small INSERM UMR 1162, Gènomique Fonctionnelle des Tumeurs Solides,
number of mortality we couldn’t reach statistical significance for Paris, France, 4 INSERM, UMR 1162, Gènomique Fonctionnelle des
overall survival. Tumeurs Solides, Institut Universitaire d'Hèmatologie, Paris, France,
5
Conclusion: We observed significant correlation between NAC re- Department of Pathology, Hôpital Bichat AP-HP, France,
6
sponses of primary tumour and axilla. Both CR and PR of pri- INSERM UMR 1149, Centre de recherche sur l'inflammation, Paris,
mary tumour and axilla were independent predictors of DFS. France

Background & Objectives: The presence of microvascular invasion

Monday, 9 September 2019, 17:15 - 19:15, Apollon (mVI) is a major risk factor of tumour recurrence after surgery and mor-
OFP-05 | Digestive Diseases Pathology – Liver / Pancreas tality in hepatocellular carcinoma (HCC). mVI is only detectable by mi-
croscopic examination of the surgical specimen. The goal of our study
was to define a gene expression signature associated with mVI in HCC,
OFP-05-001 applicable on formalin fixed-paraffin embedded (FFPE) biopsies using a
Tumour-intrinsic mechanisms drive the immune contexture in pan- Nanostring approach.
creatic cancer Methods: A total of 108 FFPE archived HCC samples were included, of
H. Sadozai1, M. Wartenberg1, T. Gruber1,2, M. Schenk1, I. Zlobec3, J. which 69 preoperative biopsies were available with a paired surgical
Brugger1, B. Gloor4, E. Vassella1, A. Perren1, E. Karamitopoulou1 specimen. Total mRNAs were extracted from samples. Gene expression
1
Institute of Pathology, University of Bern, Switzerland, 2 Graduate was assessed using Nanostring technology. In a training set of 69 HCC
School for Cellular and Biomedical Sciences, University of Bern, samples (39 surgical samples and 30 biopsies), we defined a gene expres-
Switzerland, 3 University of Bern, Switzerland, 4 Department of sion signature associated with mVI based on expression of 200 genes.
Visceral Surgery and Medicine, Inselspital University Hospital Bern This mVI signature was validated in an independent set of 39 biopsies.
and University of Bern, Switzerland Results: Training and validation sets were similar for all clinico-
pathological criteria particularly on mVI (52% vs 67%, p=0.14). A 10
Background & Objectives: The biological mechanisms underlying the gene-signature, strongly associated with mVI, was obtained in the train-
immune profiles of pancreatic ductal adenocarcinoma (PDAC) are poorly ing set. In the validation set, this signature predicted mVI with an accu-
understood and warrant further investigation as they can unveil novel racy of 82%. The sensitivity and the specificity were respectively of 0.92
treatment strategies. We compared the immune, genetic and morphologic and 0.62. Of note, there was an excellent correlation of gene expression
characteristics of three survival-stratified PDAC-cohorts to identify between biopsies and corresponding surgical samples (14 paired speci-
survival-associated profiles. mens, mean correlation index = 0.92 [0.87-0.95]).
 Virchows Arch

Conclusion: This study provides a relevant surrogate signature of mVI in analysed. Data of follow-up of patients for recurrence and cancer-related
HCC, that may be applied in clinical practice on routine tumour biopsy, events were retrieved from patients’ archives.
and then integrated into the therapeutic strategy of patients. Results: HCCs pre-operatively treated with TACE showed significantly
higher PDL-1 expression by tumour cells than those with no prior TACE
(2% vs 0.36%, P <0.001). Expression of PD-1 and PDL-1 by inflamma-
OFP-05-003 tory cells was significantly higher in resected tumours than in correspond-
Imaging mass spectrometry to differentiate between pancreatic ade- ing biopsies obtained before TACE (9.1% vs 1.4% and 9.5% vs 1.8%
nocarcinoma and cholangiocarcinoma respectively, P < 0.001).
C. Bollwein1, A. Jacob1, J. Pereira Lopes Goncalves1, S. Deininger2, K. Conclusion: Treatment by TACE seems to induce an increase in PD-1
Schwamborn1, W. Weichert1 and PDL-1 expression in HCC. This may induce better response to im-
1
Technical University of Munich, School of Medicine, Institute of mune checkpoint inhibitors which could be considered as a line of treat-
Pathology, Germany, 2 Bruker Daltonik GmbH, Bremen, Germany ment in these patients.

Background & Objectives: Both pancreatic adenocarcinoma and chol- Supported by Science and Technology Development Fund (STDF),
angiocarcinoma originate from epithelial cells of the pancreatico-biliary Institut Francais d'Egypte (IFE)
system. The histomorphological similarities between both carcinomas
represent a challenge in pathological diagnostic. Imaging mass spectrom-
etry (IMS) allows the visualization of protein/peptide expression profiles OFP-05-005
in a spatially resolved manner and enables direct correlation with histo- Vessels encapsulating tumour clusters (VETC) is a powerful predic-
logical features, thus offering an unbiased approach for tissue tor of aggressive hepatocellular carcinoma (HCC)
classification. S. Renne1, H.Y. Woo2, N. Rudini3, S. Allegra3, H. Yano4, M. Donadon5,
Methods: Tissue microarrays comprising samples from pancreatic ade- L. Viganò5, J. Akiba6, H. Sun Lee7, H. Rhee8, Y.N. Park2, M. Roncalli3,9,
nocarcinoma (n=107) and cholangiocarcinoma (n=122) were subjected to L. Di Tomaso3,9
1
on-tissue tryptic digestion and incubated in a humid environment follow- Humanitas Clinical and Research Center - IRCCS, Italy, 2 Department
ed by matrix application (alpha-cyano-4-hydroxycinnamic acid) using an of Pathology, Yonsei University College of Medicine, Seoul, Republic of
automated sprayer. Samples were analysed utilizing a Bruker RapifleX Korea, 3 Department of Pathology, Humanitas Clinical and Research
MALDI-TOF mass spectrometer. Subsequently, matrix was removed, Center - IRCCS, Rozzano, Italy, 4 Department of Pathology, Kurume
sections were stained by hematoxylin and eosin and scanned using the University School of Medicine, Japan, 5 Department of Hepatobiliary
Aperio slide scanner for histopathological annotation. Data analysis was Surgery, Humanitas Clinical and Research Center - IRCCS, Rozzano,
performed by using the SCiLs Lab and FlexImaging 5.0 software. Italy, 6 Department of Diagnostic Pathology, Kurume University
Results: For statistical analysis the sample set was divided into a training Hospital, Japan, 7 Biostatistics Collaboration Unit, Yonsei University
(60% of samples), a validation (20% of samples), and a test set (20% of College of Medicine, Seoul, Republic of Korea, 8 Department of
samples). In the test set, 21 out of 22 pancreatic adenocarcinoma samples Radiology, Yonsei University College of Medicine, Seoul, Republic of
and 23 out of 27 cholangiocarcinoma samples could be classified Korea, 9 Department of Biomedical Sciences, Humanitas University,
correctly. Rozzano, Italy
Conclusion: IMS could reliably differentiate between pancreatic adeno-
carcinoma and cholangiocarcinoma. Thus, this technology might offer an Background & Objectives: A vascularization pattern named VETC
alternative way to aid in everyday pathology practice. was recently described to be related to rapid tumour dissemination
and high recurrence rates. Our aim was to evaluate VETC against
consolidated and novel prognostic markers on a large series of
OFP-05-004 surgically resected HCC with various etiologies from different geo-
Transarterial chemoembolisation enhances programmed death-1 graphic areas.
and programmed death ligand-1 expression in hepatocellular Methods: VETC was assessed in a large multi-institutional cohort of
carcinoma 544 resected HCC cases from Italy, Korea and Japan, and matched
A. Montasser1,2, A. Beaufrère1,3, F. Cauchy4, O. Soubrane4, N. Colnot1, against a full spectrum of clinical and pathological variables. VETC,
S. Tessiore1, M. Albuquerque1,3, V. Paradis1,3 documented using CD34 immunostaining, was easily reproducible
1
Pathology Department, Beaujon University Hospital, AP-HP, Clichy, and reliably detectable in whole sections and small sized tissues of
France, 2 Pathology Department, Theodor Bilharz Research Institute, TMA.
Giza, Egypt, 3 INSERM U1149, Beaujon University Hospital, Clichy, Results: VETC-HCC were detected in 18.9% of the cases. VETC
France, 4 Department of HPB and Pancreatic Surgery, Beaujon was significantly associated to several clinical and pathological fea-
University Hospital, AP-HP, Clichy, France tures such as: AFP level, tumour size >5 cm, Edmonson grade,
macrotrabecular pattern, compact pattern, inflammatory infiltrates,
Background & Objectives: Over 70% of Hepatocellular Carcinomas and microvascular invasion. VETC was associated with early recur-
(HCCs) are diagnosed at advanced stage and are candidates to rence [HR: 1.52 (1.06-2.19), p= 0.023], worse OS [HR: 2.26 (1.37-
locoregional treatment and/or Sorafenib therapy with low response rate, 3.72), p= 0.001] and DFS [HR: 1.66 (1.21-2.27), p= 0.002] at mul-
short overall survival and high cost. With the introduction of immune tivariable analysis. VETC impacted on survival in patients stratified
checkpoint inhibitors as modalities of cancer treatment, we aim to evalu- for etiology (HCV/HBV), vascular invasion and specific molecular
ate the potential of transarterial chemoembolization (TACE) to induce phenotypes (β-catenin/GS+). This peculiar vascular pattern was
immune profile changes in HCC. enriched in the recently reported macro-trabecular massive HCC sub-
Methods: A total of 73 surgically-resected HCCs with (23) and without type, which was seen in 7.9% (43/544) and associated with high AFP
(50) preoperative TACE were included in the study. The immunohisto- levels, poor tumour differentiations.
chemical expression of PD-1 and PDL-1 was assessed in both groups in Conclusion: VETC pattern was easily detectable in a consistent fraction
relation to clinical features, status of non-tumoural liver, morphologic of HCC and was a powerful pathological finding impacting on survival.
characteristics of the tumour, mismatch repair status, and digitally com- The study of this pattern promises to be a new tool to further accommo-
puted tumour/stroma ratio. Biopsies realized before TACE were similarly date HCC therapy to the intrinsic tumour biology.
Virchows Arch

This study was supported by the National Research Foundation of Methods: This bicentric, retrospective study is based on a cohort of
Korea (NRF) funded by the Korean Government (MSIP) (No. 424 PDAC diagnosed between 2004 and 2017, in Hospice Civils de
NRF-2017R1A2B4005871, NRF-2017M3A9B6061512, NRF- Lyon. All the slides were reviewed by two pathologist, including one
2016M3A9D5A01952416). expert, blindfold to independently retrieved survival data. SMAD4
status was assess based on immunohistochemistry (Ventana
UltraBench, clone SP306).
OFP-05-006 Results: Patients with SMAD4 deficient tumour have a worse prognosis
Intraductal papillary neoplasm of the bile duct: clinicopathological with decreased OS compared to those with SMAD4 expressing tumours
characteristics and insulin-like growth factor II mRNA binding pro- (respectively 1208 days vs 1559 days, p < 0.05). Moreover we found that
tein 3 (IMP3) expression in 24 cases SMAD4 deficient tumours present more often perineural invasion (p<
E. Buyuktalanci1, A. Damirli2, F. Tekin3, A. Uğuz4, îV. Unalp4, M. 0.01), necrosis (p < 0.05), higher N status (p < 0.05) and higher invaded
Zeytunlu4, D. Nart1, G. Ersoz3, O. Ozutemiz3, F. Yılmaz1 nodes ratio (p < 0.01).
1
Ege University Faculty of Medicine Department of Pathology, Turkey, Conclusion: Here we report histopathological characterization of
2
Azerbaijan Republic Ministry of Health Unifıcation Forensic Medical SMAD4 deficient tumours. We also confirm the worse prognosis of these
Expertise and Pathological Anatomy, Azerbaijan, 3 Ege University tumours and their association with necrosis, lymph node and perineural
Faculty of Medicine Department of Gastroenterology, Turkey, 4 Ege invasion.
University Faculty of Medicine Department of General Surgery, Turkey

Background & Objectives: Intraductal papillary neoplasm of the bile OFP-05-008

duct (IPNB) is rare but is one of the precursors of cholangiocarcinoma Quantitative analysis of tumour budding and subcellular localisation
(CC). The oncofetal protein IMP3, is proposed as a marker for high-grade of E-cadherin on a cohort of periampullary carcinomas - a machine
dysplasia in the biliary tract. In this study the clinicopathologic charac- learning approach
teristics and IMP3 expression of IPNB are analysed. E. Kocsmar1, G. Lotz1, A. Kiss2, M. Hoerner3, E. Petrova4, S. Timme3,
Methods: Clinicopathologic data of 24 IPNB cases operated between A. Csanadi3, M. Werner5,6,7, U. Wellner4, P. Bronsert5,6,7
1
2000 and 2018 were retrospectively analysed. Immunohistochemical 2nd Department of Pathology, Faculty of Medicine, Semmelweis
staining for IMP3 antibody was performed. Statistical analyses were University, Hungary, 2 2nd Department of Pathology, Semmelweis
made using SPSS. University, Hungary, 3 Institute of Surgical Pathology, University
Results: There were 15 female and 9 male patients with a mean age of 58 Medical Center Freiburg, Germany, 4 Department of Surgery, UKSH
(44-76, range). Tumour locations were: intrahepatic (41.7%), hilar Campus Lübeck, Germany, 5 Department of Surgical Pathology,
(20.8%) and extrahepatic (37.5%). The mean tumour size was 4.42 cm University of Freiburg, Faculty of Medicine, Germany, 6 German
(1.5-12, range). Epithelial subtypes were pancreatobiliary (83.4%), intes- Cancer Consortium (DKTK) and German Cancer Research Center
tinal (8.3%) and mixt (8.3%). The degree of dysplasia was low (12.5%), (DKFZ), Heidelberg, Germany, 7 Tumourbank Comprehensive Cancer
intermediate (8.3%) and high (75%). Of the 24 cases, 5 were non-inva- Center, University of Freiburg, Faculty of Medicine, Germany
sive, 4 were focally invasive (FI) and 15 were invasive (20.8%, 16.6%
and 62.5%, respectively). Perineural invasion (PI) was detected in 20.8%, Background & Objectives: Tumour budding and the closely related
vascular invasion in 37.5% and lymph node metastasis (LNM) in 16.7% epithelial mesenchymal transition (EMT) have prognostic impact on
of the cases. IMP3 was expressed in 20%, 50% and 100% of non-inva- overall survival. However, precisely quantified evaluations of cor-
sive, FI and invasive tumours, respectively. Invasive tumours had signif- relation between tumour cell cluster (TCC) size, EMT and prognosis
icantly higher IMP3 expression than non-invasive or FI tumours (p: are still missing. Our aim was to classify the periampullary carcino-
0.017). Presence of PI and LNM were significantly correlated with over- mas (PC) into groups according to their budding behavior and EMT
all survival (p:0.01 and p:0.000, respectively) regardless of the location of signature and use machine learning approaches to predict patients’
the tumour and IMP3 status. outcome.
Conclusion: Our data confirms the importance of IMP3 as a marker for Methods: PC samples of 172 patients were stained with E-
invasion but not as a prognostic determinant. cadherin immunohistochemistry. Cell number and EMT features
of invasion front TCCs were evaluated by assessing fractions of
cells with different subcellular localization of E-cadherin (mem-
OFP-05-007 branous, cytoplasmic, mixed). Elastic net penalized feature selec-
SMAD4 deficient pancreatic adenocarcinoma are poor prognosis tu- tion was performed on 5 cell intervals of TCC sizes and relating
mours associated with histopathological aggressive features cell fractions with membranous, cytoplasmic or mixed E-cadherin
T. Fenouil1, C. Caligaris2, A. Bertrand2, S. Santis2, L. Bartholin2, V. expression. Prognostic significance of the defined budding catego-
Hervieu1 ries were entered into subsequent Cox regression model with stan-
1
Hospices Civils de Lyon, France, 2 Centre de Recherche en dard clinicopathological parameters.
Cancerologie de Lyon, France Results: Overall median of TCCs/tumour was 42 (range: 3-283)
and TCC size was 16 cells (range: 2-36 cells). Number of TCCs
Background & Objectives: Pancreatic ductal adenocarcinoma (PDAC) in a given interval inversely correlated with their size (p<0.001).
is a highly lethal cancer characterised by incidence/death ratio close to 1. Feature selection identified 6-10 cell and 31-35 cell TCCs as
Besides it is expected to become the second cause of death by cancer in having prognostic value, moreover, the cytoplasmic E-cadherin
2030. The major steps of PDAC carcinogenesis are the activation of expression in TCCs of 10-15 and 26-30 cells. In multivariate
KRAS oncogene followed by inactivation of tumour suppressor genes. model, budding category was an independent prognostic factor
Loss of SMAD4 occurs in approximately 60% of tumours as a late event (p<0.001).
in carcinogenesis. A certain number of studies try to assess the prognostic Conclusion: Machine learning-based detailed quantitative analysis of
role of SMAD4 loss using immunohistochemistry in order to better strat- invasion front TCCs demonstrated that not only tumourbuds (<5 cells)
ify patients, without reproducible results. This study aim to confirm the but also bigger TCCs have strong prognostic impact in the periampullary
reduction of overall survival (OS) in SMAD4 deficient tumours and better carcinomas, contributing to establishing a more advanced grading
characterise their histopathological features. system.
 Virchows Arch

OFP-05-009 Background & Objectives: Intrahepatic cholangiocarcinomas (ICC) are

Expression of GRP78 protein is increased in pancreatic ductal ade- primary tumours of the liver characterised by the presence of a
nocarcinoma, pancreatic intraepithelial neoplasia and intraductal desmoplastic stroma. Its prognostic role is still an open question. In ma-
papillary mucinous neoplasm lignancies, tumour stroma may be benefit, acting as a barrier against
X. Ding1, B. Trac1, X. Duan1 cancer diffusion or pejorative, by supporting the tumoural cells. The
1
Loyola University Medical Center, USA aim of the present study was to evaluate the prognostic value of stromal
compartment in ICC through a multiparametric morphological analysis.
Background & Objectives: The poor prognosis of pancreatic ductal ade- Methods: Forty-nine patients (61 years) with ICC surgically resected were
nocarcinoma (PDAC) is associated with late detection, aggressive tumour included. For all cases, tumour paraffin blocks of ICC were selected. Stromal
biology and chemotherapeutic resistance. According to the Response area and Cancer-Associated Fibroblats (CAF) number, were automatically
Evaluation Criteria in Solid Tumours (RECIST), for pancreatic cancer pa- quantified on Sirius red staining and alpha smooth muscle actin expression,
tients treated palliatively with gemcitabine and nab-paclitaxel, no complete respectively. Activated stroma index (ASI) was calculated as the ratio of
responses were observed, and partial response was only observed in 37% of CAF number and stromal area. Collagen fiber reticulation properties were
patients, and progressive disease in 22% of patients. GRP78 is a major analysed using second harmonic generation imaging.
endoplasmic reticulum (ER) chaperone protein critical for protein quality Results: High stromal area was inversely correlated with vascular inva-
control of ER, It is found that GRP78 is preferably required for cancer cell sion (62.5% vs 95.7%, p=0.006) and positively correlated with well dif-
survival, promotes tumour progression and enhances drug resistance. The ferentiated tumours (60% vs 12.5%, p=0.001). Patients with high stromal
study aims to explore whether the expression of GRP78 protein in PDAC, area had a better disease free survival (DFS) than patients with low stro-
pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucin- mal area (60 % vs 10 %, p=0.077). Low ASI was correlated with a better
ous neoplasm (IPMN) is increased compared to the normal pancreatic ducts DFS (60% vs 10%, p=0.05). High collagen reticulation index was corre-
using immunohistochemical (IHC) staining method. lated with a worsened overall survival (42% vs NR, p=0.026).
Methods: The expression of GRP78 were assessed using IHC in 45 cases Conclusion: Desmoplastic stroma seems to exert protective effect in
of formalin-fixed paraffin-embedded tissues, in which normal ducts (38), patients with ICC. Stromal collagen reticulation may provide additional
high grade PanIN (PanIN-HG, 16), low grade PanIN (PanIN-LG, 14), clinically relevant information in malignancies.
low grade IPMN (IPMN-LG, 26), high grade IPMN (IPMN-HG, 9), and
PDAC (20) were examined. Immunostaining intensity of GRP78 protein
was categorized as no or weak staining (0-1+) and strong staining (2-3+). OFP-05-011
Fisher’s exact test with two tails was performed using the GraphPad MSI in intestinal immunophenotype in ampullary and pancreatic
statistical software. cancer
Results: GRP78 expression was identified in cytoplasm of normal pan- G. Setdikova1, E. Eremeeva1, O. Paklina1, D. Rotin1,2
1
creatic ducts, IPMN and PDCA with a fine granular pattern. All PDAC, Botkin Clinical Hospital, Russia 2 Hospital Haim Sheba, Tel-ha-
PanIN-HG and IPMN-HG show strong expression of GRP78 while the Shomer, Ramat Gan, Israel
normal ductal cells show only minimal expression of GRP78. 73% of
IPMN-LG and 30% PanIN-LG expresses GRP78 strongly. Statistical Background & Objectives: Dual IHC pattern (intestinal and pancreatic)
analysis revealed significant difference in GRP78 expression level be- is usual in ampullary carcinoma (AC) and pancreatic ductal adenocarci-
tween normal ductal cells and all five pathological conditions including noma (PDA). They report that Microsatellite instability (MSI) occurs
PDCA, PanIN-HG, PanIN-LG, IPMN-HG and IPMN-LG (all p<0.0001). more frequently in AC than in PDA.
The aim is to estimate the frequency of MSI microsatellite instability and
to compare obtained data in intestinal IHC pattern of AC and PDA.
Normal ducts IPMN-LG IPMN-HG PanIN-LG PanIN-HG PDAC Methods: 60 cases with intestinal IHC pattern (CK20 +, Muc 2 +) - 30 of
AC and 30 of PDA) were evaluated. The determination of mismatch
Total 38 26 9 14 16 20
repair deficiency was identified by means of 4 IHC antibodies panel
including the markers MLH-1, PMS2, MSH2, MSH6.
No or weak staining 37 7 0 10 0 0
Results: MSI in AC group was found in 57% (17/30) of cases. The
(0-1+)
majority of cases (12/17) (71%) demonstrated the deficiency of the
Strong staining (2-3+) 1 19 9 4 16 20
PMS2 of mismatch repair protein. The combinations of MLH1/PMS2
% of strong staining 3% 73% 100% 30% 100% 100% and MSH2/MSH6 occurred in 2/17 and 3/17, respectively. In PDA group
MSI was determined only in 2/30 (7 %) cases (MLH1/PMS2). In all 60
cases, there was no history of familial disease neither signs of
Conclusion: This study shows that the expression level of GRP78 is synchronous/metachronous tumours of other locations. No statistically
significantly increased in PDAC, PanIN and IPMN compared to the nor- significant association between the presence of MMR in AC and patho-
mal ductal cells. It appears that there is a progressive increase in GRP78 logical pattern of the tumour.
expression from IPMN-LG and PanIN-LG to IPMN-HG and PanIN-HG, Conclusion: The study showed that MSI is common in AC with intesti-
and to PDAC. Increased GRP78 expression may contribute poor respon- nal phenotype. The prognostic, predictive and diagnostic role of that
siveness of PDCA to conventional chemotherapy. phenomena needs further investigations.

OFP-05-010 OFP-05-012
Prognostic value of desmoplastic stroma in intra-hepatic PTEN protein expression in pancreatic ductal adenocarcinoma: rel-
cholangiocarcinoma evance for tumour biology and relationships to AKT and TGF-beta
N. Guedj1, L. Blaise1, F. Cauchy2, A. Beaufrère1, M. Albuquerque3,4, O. pathways proteins
Soubrane2, M. Ronot1, V. Paradis3,4 A. Handra-Luca1
1
Hopital Beaujon, France, 2 Department of HPB and Pancreatic Surgery, 1
APHP University Paris Nord, France
Beaujon University Hospital, AP-HP, Clichy, France, 3 Pathology
Department, Beaujon University Hospital, AP-HP, Clichy, France, Background & Objectives: PTEN is considered a tumour suppressor of
4
INSERM U1149, Beaujon University Hospital, Clichy, France the AKT/mTOR pathway. Animal model studies have shown that loss of
Virchows Arch

PTEN function is involved in the progression of pancreatic cancer. K- that the target antigens of IgG4 thyroiditis are thyroglobulin and its iso-
RAS signaling, by interfering with TGF-beta and PTEN (Chow et al, forms. As thyroglobulin is an organ-specific protein, this observation is
2007) may result in a switch mechanism from growth suppression to consistent with the solitary nature of IgG4 thyroiditis.
growth promotion in pancreatic cancers.
We aimed to study the relevance of PTEN expression in pancreatic ade-
nocarcinomas (PDAC). OFP-06-002
Methods: We examined immunohistochemical expression of PTEN pro- Is preoperative RAS or BRAF K601E mutations cytologic detection
tein in a series of 99 PDAC treated by surgery (without neoadjuvant useful for clinical management of indeterminate thyroid nodules,
treatment). Protein expression patterns were analysed with regard to tu- according to the new WHO classification?
mour features and to AKT and TGFbeta pathway protein expression L. Ravella1, J. Lopez2,3, F. Descotes4, J. Giai5,6, V. Lapras7, M. Denier7, F.
(mTOR and SMAD4, respectively). Borson-Chazot8, J. Lifante9, M. Decaussin-Petrucci10
1
Results: PTEN was expressed in 54 PDACs in a nuclear pattern and in 12 Pathology Department, Centre Hospitalier Lyon Sud, Hospices Civils
tumours in a cytoplasmic pattern. Nuclear PTEN was higher in T2 de Lyon, Pierre Bènite, France, 2 Biochemistry and Molecular Biology
PDACs as compared to T1 PDACs (as well as mTOR) and was decreased Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon,
in T3 PDACs as compared to T2 PDACs (as well as mTOR and SMAD4) Pierre Bènite, France, 3 Cancer Research Center of Lyon, Team EMT
(p<0.05 for all comparisons). Nuclear PTEN correlated to cytoplasmic and cancer cell plasticity, Lyon 1 University, France, 4 Department of
mTOR and to nuclear SMAD4 (p<0.01). Biochemistry, Molecular Biology, Centre Hospitalier Lyon Sud,
Conclusion: The results of our study indicate a complex role for PTEN in Hospices Civils de Lyon, Pierre Benite, France, 5 CNRS, UMR 5558,
pancreatic carcinogenesis, possibly at the step of extrapancreatic tumour Laboratoire de Biomètrie et Biologie Evolutive, Equipe Biostatistique-
invasion. The relationship between PTEN and SMAD4 only with regard Santè, Villeurbanne, France ; Universitè Lyon 1, Villeurbanne, France,
6
to extrapancreatic T3 stage tumours (and not with T1 stage tumours) may Hospices Civils de Lyon, Service de Biostatistique et Bioinformatique,
explain a stage-specific interaction and role. France, 7 Radiology Department, Centre Hospitalier Lyon Sud, Hospices
Civils de Lyon, Pierre Bènite, France, 8 Endocrinology Department,
This project was supported by the SNFGE. Groupement hospitalier Est, Hospices Civils de Lyon, Bron, France,
9
Endocrine Surgery Department, Centre Hospitalier Lyon Sud,
Hospices Civils de Lyon, Pierre Bènite, France, 10 Department of
Monday, 9 September 2019, 17:15 - 19:15, Hermès Pathology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon,
OFP-06 | Joint Session: Endocrine Pathology / Head Universite Lyon 1, Pierre Benite, France
and Neck Pathology
Background & Objectives: The diagnostic value of RAS and K601E
BRAF mutations in fine-needle aspiration of thyroid indeterminate cyto-
OFP-06-001 logic nodules is not well established. Our aim was to evaluate the histo-
IgG4 thyroiditis: similarity to and differences from IgG4-related logic characteristics, the risk of malignancy associated with such muta-
disease tions and their potential interest for preoperative clinical management of
K. Kakudo1, K. Inomata2, Y. Li3 nodules.
1
Department of Pathology, Kindai University Nara Hospital, Japan, Methods: We evaluated 69 indeterminate thyroid nodules with RAS or
2
Department of Clinical and Laboratory Medicine, Yamashita Thyroid K601E BRAF mutations. All cytologic specimens were indeterminate ac-
Hospital, Japan, 3 Department of Pathology, Shandong Provincial cording to the thyroid Bethesda System. Diagnosis of malignant, benign or
Hospital, China indolent neoplasms was classified according to the 2017 WHO classifica-
tion. Carcinoma, NIFTP (Non-Invasive Follicular Thyroid neoplasm with
Background & Objectives: IgG4-related disease (RD) is clinically Papillary like features) and WDTUMP (well-differentiated tumour of
characterised by tumour-like enlargement of affected organs, increased se- uncertain malignant potential) were considered “surgical”, as they require
rum IgG4 levels and the alleviation of symptoms after steroid therapy. surgical excision. Adenoma was considered “non-surgical”. The risk of
Pathologically, it is characterised by lymphoplasmacytic infiltration, sclerosis malignancy and the risk of “surgical pathology” were evaluated.
and an increased number of IgG4-positive plasma cells. In 2009, our group Results: Pathologic evaluation of the 69 mutated nodules demonstrated
first reported the infiltration of IgG4-positive plasma cells in a subset of benign, indolent and malignant histology in 17 cases (25%), 21 cases
Hashimoto’s thyroiditis (HT). HT can be divided into IgG4 thyroiditis (30%) and 31 cases (45%) respectively. The risk of malignancy was
(aggresive subtype) and non-IgG4 thyroiditis (good prognosis group). 45%, and the risk of surgical pathology was 75%. The majority of carci-
Methods: A total of 120 cases of HT from 5 Asian hospitals were retro- nomas were follicular variant of PTC (Papillary Thyroid Carcinoma).
spectively collected. Quantitative assessment of IgG4 staining was per- Conclusion: Preoperative RAS or BRAF K601E mutations detection in
formed on 120 surgically treated thyroid glands with HT. The clinical cytologic indeterminate thyroid nodules carries a high risk of surgical
data, including demographic information, clinical, laboratory and sono- pathology, and may benefit from a surgical management. Most surgical
graphic findings, medical history, treatments, and disease outcomes, were lesions harboring those mutations are low risk follicular variant of PTC or
obtained from the referral forms submitted at the time of the operation and NIFTP, which may be in favor of an initial lobectomy.
patients’ medical records.
Results: The 120 cases were divided into 33 (27.5%) IgG4 thyroiditis
cases and 87 (72.5%) non-IgG4 thyroiditis cases using cutoff points (20 OFP-06-003
IgG4-positive plasma cells per high-power microscopic field and Risk stratification for pheocromocytoma and paraganglioma: a com-
IgG4/IgG ratio of 30%) proposed by our group. The following parameters parison of pathological scores for prediction of metastatic potential
were significantly different between IgG4 thyroiditis and non-IgG4 thy- F. Ambrosi1, A. De Leo2, M. Grillini3, S. Selva3, G. Zavatta3, G. Di
roiditis; age at surgery (52.3 vs 58.1 years old), male to female ratio (25.9 dalmazi3, D. Santini1, C. Ceccarelli2
vs 5.4%), serum IgG4 level (263.7 vs 80.9 mg/dL) and subclinical hypo- 1
Pathology Unit, Sant'Orsola-Malpighi Hospital, University of Bologna,
thyroid status (45.5 vs 12.0%). Italy, 2 Pathology Unit, Department of Experimental, Diagnostic and
Conclusion: IgG4 thyroiditis is a destructive fibro-inflammatory lesion Specialty Medicine, S. Orsola-Malpighi Hospital, University of
and has a higher risk for hypothyroid status. Systemic involvement was Bologna, Italy, 3 Department of Medical and Surgical Sciences, S.
not found in our IgG4 thyroiditis cases. Recently, Inomata et al. reported Orsola-Malpighi Hospital, University of Bologna, Italy
 Virchows Arch

Background & Objectives: The Grading system for Adrenal Group C, subcapsular tumour >5 mm; Group D, capsular tumour >5
Pheochromocytoma and Paraganglioma (GAPP) has been proposed for mm. Univariate analysis demonstrated significant differences between
predicting the metastatic potential in pheochromocytoma and the four groups, with Group D showing the most aggressive features
paraganglioma (PPGL) to overcome the limitations of the and Group A the most indolent ones. Multivariate analysis correlated
Pheochromocytoma of the Adrenal Scaled Score (PASS). The objective Group D tumours with (i) microscopic features: presence of psammoma
of the study was to compare PASS and GAPP scoring systems for risk bodies within the tumour, tall cell features, tumour fibrosis, with an in-
assessment in a single-institution case series. verse correlation to follicular growth pattern; (ii) characteristics of tumour
Methods: GAPP and PASS scores were assessed and compared in 50 growth: infiltrative border, unicentric tumour with intraglandular tumour
consecutive PPGLs. Immunohistochemistry for SDHA/SDHB was per- spread, vascular invasion, psammoma bodies in the parenchyma sur-
formed for each case. rounding the tumour; (iii) clinicopathologic features: tall cell or classic
Results: Lymph-node metastasis occurred in 8% (4/50) of patients, with a papillary carcinoma diagnoses, BRAFV600E mutation, lymph node me-
mean follow-up of 40.7 months. According to GAPP score, 26% (13/50) tastases, ATA risk group, with an inverse correlation to nodular hyperpla-
of cases were well-differentiated, 62% (31/50) moderately-differentiated sia, to the presence other thyroid neoplasms, to a diagnosis of Papillary
and 12% (6/50) poorly-differentiated. Based on GAPP score, all well- microtumour or to that of NIFTP.
differentiated PPGLs were non-metastatic, while 2/31 (6.5%) Conclusion: Group D mPTCs have unfavourable features and likely
moderately-differentiated and 2/6 (33.3%) poorly-differentiated PPGLs endowed with the potential to progress to clinically relevant tumours.
were metastatic. In contrast, PASS score ≥4 resulted in 66% of cases. Group A mPTCs show bland features and likely have limited malignant
Metastasis occurred in 1/17 (5.9%) PPGL with a PASS <4 and 3/33 potential.
(9.1%) PPGLs with a PASS ≥4. Therefore, GAPP scoring system signif-
icantly predicted metastasis (p=0.05), in contrast to PASS (p=0.82). The
metastatic disease didn’t correlate with ki-67 index and mitotic activity. OFP-06-005
Loss of SDHB resulted in 10.6% (5/47) PPGLs: four cases moderately- Immunohistochemical evaluation of CXCR4 chemokine receptor ex-
differentiated and one poorly-differentiated with metastatic disease. pression in metastatic and nonmetastatic well-differentiated pancre-
Conclusion: The GAPP scoring system is a valid tool to discriminate atic neuroendocrine tumours
PPGLs with benign behavior and to predict the metastatic disease. V. Delektorskaya1, O. Solovieva1, Y. Patyutko1
1
However, other prognostic criteria are required in order to assess the N.N. Blokhin National Medical Research Center of Oncology, Russia
metastatic potential in moderately-differentiated PPGL group, and
GAPP should be integrated into a multidisciplinary approach for better Background & Objectives: Pancreatic neuroendocrine tumours
management of patients. (PanNETs) are a heterogeneous group of neoplasms with unpredictable
clinical course and biological behaviour. CXCR4 chemokine receptor
overexpression is associated with tumour progression, invasion, angio-
OFP-06-004 genesis, and metastasis in various types of tumour. Data on CXCR4
Does the site of the origin of the microcarcinoma within the thyroid expression in pancreatic neuroendocrine neoplasms are limited. We
matter? A multicenter pathologic and clinical study for risk aimed to assess the prevalence and prognostic significance of CXCR4
stratification expression in both primary and metastatic PanNETs.
A. De Leo1, A. Repaci2, M.L. Bacchi Reggiani3, D. De Biase4, D. Di Methods: CXCR4 expression was evaluated by immunohistochemistry
Nanni5, C. Di Gioia6, G. Grani7, E. Solaroli8, C. Durante7, S. Filetti7, G. using the monoclonal rabbit anti-human CXCR4 antibody UMB-2 on a
Tallini9 panel of 52 primary metastatic and nonmetastatic PanNETs and 20 liver
1
Pathology Unit, Department of Experimental, Diagnostic and Specialty metastases. The expression was correlated with clinicopathological data
Medicine, University of Bologna, S. Orsola-Malpighi Hospital, Italy, and prognosis.
2
Endocrinology Unit, Department of Medical and Surgical Sciences, Results: Membrane positivity for CXCR4 was detected in 17/52
University of Bologna, S. Orsola-Malpighi Hospital, Italy, 3 Department primary PanNETs (32.7%, 12 metastatic and 5 nonmetastatic) and
of Experimental, Diagnostic and Specialty Medicine, University of in 7/20 liver metastases (35.0%). CXCR4 was expressed with a
Bologna, S. Orsola-Malpighi Hospital, Italy, 4 Department of Pharmacy high IRS in metastatic G3 tumours. CXCR4 expression was as-
and Biotechnology (Dipartimento di Farmacia e Biotecnologie) - sociated with higher WHO grade, Ki-67 index, and distant metas-
Molecular Diagnostic Unit, Azienda USL di Bologna, University of tasis (p < 0.001). Furthermore, CXCR4 was positively related to
Bologna, Italy, 5 Pathology Unit, S. Orsola-Malpighi Hospital, loss of ATRX/DAXX nuclear expression and negatively PR and
University of Bologna, Italy, 6 Department of Radiological, Oncological SSTR 2A staining patterns. However, no statistical differences
and Pathological Sciences, "Sapienza" University of Rome, Italy, were found between CXCR4 expression and PanNET prognosis.
7
Department of Internal Medicine and Medical Specialties, "Sapienza" Conclusion: The expression of CXCR4 is associated with tumour pro-
University of Rome, Italy, 8 Endocrinology Unit, Ospedale Maggiore, gression and frequently observed in more advanced and metastatic
Bologna, Italy, 9 Department of Medicine (Dipartimento di Medicina PanNETs. CXCR4 may represent a potential tissue-based biomarker of
Specialistica, Diagnostica e Sperimentale) - Molecular Diagnostic Unit, an aggressive phenotype among PanNETs.
Azienda USL di Bologna, University of Bologna School of Medicine,
Italy
OFP-06-006
Background & Objectives: Risk stratification of papillary Papillary thyroid carcinoma: phenotypical and molecular differenti-
microcarcinoma (mPTC) is problematic. This study analyses the impact ation by microRNA profiling
of the mPTC origin within the thyroid on clinicopathologic features. F. Galuppini1,2, M. Fassan2, S. Barollo3, N. Valeri4, L. Cascione5, M.
Methods: A multicenter cohort of 298 mPTCs from six Italian medical Rugge2, I. Merante Boschin6, C. Mian4, G. Pennelli2
1
institutions was analysed. The distance of the tumour centre from the Women's & Children's Health Department (SDB), University of Padua,
thyroid capsule was measured micrometrically and correlated with clini- Italy, 2 Pathology Unit, Department of Medicine (DIMED), University of
copathologic features and BRAFV600E. Padua, Italy, 3 Endocrinology Unit, Department of Medicine (DIMED),
Results: Four mPTC groups based on size and distance from the thyroid University of Padua, Italy, 4 Division of Molecular Pathology, The
capsule were identified: Group A, subcapsular tumour <5 mm; Group B, Institute of Cancer Research, London, United Kingdom, 5 Institute of
capsular tumour (i.e. a tumour reaching the thyroid capsule) <5 mm; Oncology Research, Università della Svizzera Italiana, Bellinzona,
Virchows Arch

Switzerland, 6 Departments of Surgical Oncologic and Gastroenterologic Conclusion: In agreement with the theory of field cancerization, FH
Sciences (DiSCOG), University of Padua, Italy correlates with higher risk of developing loco-regional recurrences and
second primaries. In our series, local outcome of OSCC seems to be
Background & Objectives: Papillary thyroid carcinoma (PTC) is a het- influenced by the biology of adjacent mucosa more than by the clonal
erogeneous neoplasia, comprising several histological variants which are architecture of the bulk of the tumour.
associated with specific mutational profiles and distinct clinical and prog-
nostic features. To better characterise these particular subtypes of PTC, This research was supported by an academic grant (AlmaIdea 2017) from
identify the microRNAs (miRNAs) expression profile represents an im- the University of Bologna.
portant step towards the comprehension of the molecular mechanism
underlying their biological behaviour. The present study aims to widely
investigate the miRNAs expression profile of PTCs cohorts with different OFP-06-008
morphology, molecular profile and biological behaviour, including Prognostic impact of DNA methylation analysis in adjacent area of
Hobnail variant, BRAF p.K601E mutated PTCs and Classic variant surgically resected oral squamous cell carcinoma during follow up
samples. L. Morandi1, D.B. Gissi2, R. Rossi2, A. Tarsitano3, A. Gabusi2, L.
Methods: Among 3,242 consecutive patients with histological diagnosis Montebugnoli2, C. Marchetti3, M.P. Foschini1
1
of PTC at University Hospital of Padua between 2008 and 2016, we Department of Biomedical and Neuromotor Sciences, "M. Malpighi"
selected a series of 35 formalin-fixed paraffin-embedded cases according Section of Anatomic Pathology at Bellaria Hospital, University of
to PTC variants and BRAF status (17 Hobnail-PTC, 9 p.K601E BRAF- Bologna, Italy, 2 Department of Biomedical and Neuromotor Sciences,
mutated PTC and 9 Classic-PTC). Comprehensive miRNA expression Section of Oral Sciences, University of Bologna, Italy, 3 Department of
profile of the series was assessed by microarray analysis with Biomedical and Neuromotor Sciences, Section of Maxillo-facial Surgery
NanoString nCounter platform and selected miRNAs were validated by at Policlinico S. Orsola-Malpighi, University of Bologna, Italy
quantitative RT-PCR and in situ hybridization (ISH).
Results: MicroRNA profiling consistently disclosed histotype and Background & Objectives: Oral Squamous Cell Carcinoma (OSCC)
mutation-specific signatures. In particular, three miRNAs (miR-21-5p, showed a significant risk to develop local recurrences or second primary
miR-146b-5p and miR-205-5p) were significantly overexpressed in the tumours during follow-up. Recently, we developed a non-invasive assay
Hobnail variant in comparison to p.K601E BRAF-mutated and classic-type based on oral brushing and DNA methylation analysis to early detect
PTCs. The validation analysis (RT-PCR and ISH) confirmed these results. OSCC. In the present study using this assay, we investigated the adjacent
Conclusion: The present study demonstrated that in PTCs specific his- area of surgical resection in a series of OSCC during follow-up for prog-
tological variants and BRAF mutations are associated with different nostic purposes.
miRNA expression profiles. Further studies may investigate the down- Methods: 42 consecutive OSCC patients were sampled during routine
stream pathogenetic role of these miRNAs in thyroid neoplasms. follow-up after 6 months from surgical treatment, brushing the regenera-
tive mucosa covering the region that underwent the surgical OSCC exci-
sion. DNA methylation level of ZAP70, GP1BB, KIF1A, ITGA4,
OFP-06-007 LINC00599, MIR193, MIR296, TERT, LRRTM1, NTM, EPHX3, FLI1
Genetic heterogeneity in adjacent normal mucosa of oral squamous and PARP15 was evaluated by quantitative Bisulfite-NGS. After calcu-
cell carcinoma is a marker of poor prognosis lating a score by Linear-Discriminant-Analysis, the samples were dichot-
L. Morandi1, A. Gabusi2, D.B. Gissi2, L. Montebugnoli2, S. Asioli1, A. omized using a predefined threshold previously developed for early di-
Tarsitano3, C. Marchetti3, T. Balbi4, M.P. Foschini1 agnosis. One-Way-ANOVA and Kaplan-Meier curves served to evaluate
1
Department of Biomedical and Neuromotor Sciences, "M. Malpighi" any significant difference between patients who experienced a second
Section of Anatomic Pathology at Bellaria Hospital, University of neoplastic manifestation and the group who did not.
Bologna, Italy, 2 Department of Biomedical and Neuromotor Sciences, Results: 6/42 (14,3%) patients developed a second neoplastic manifesta-
Section of Oral Sciences, University of Bologna, Italy, 3 Department of tion during follow-up period (mean follow-up: 14.3 months), of which 5
Biomedical and Neuromotor Sciences, Section of Maxillo-facial Surgery showed a positive methylation score. Additional 11 patients exceeded the
at Policlinico S. Orsola-Malpighi, University of Bologna, Italy, 4 Unit of threshold but up to date they have not experienced any second manifes-
Anatomic Pathology, S. Orsola Hospital, Bologna, Italy tation. Among the remaining 26 negatives, only one developed a recur-
rence. A positive score correlated with a worse locoregional control of
Background & Objectives: Intra-tumoural heterogeneity (ITH) disease (p<0.05).
displayed by tumour cells represents a diagnostic challenge when Conclusion: The DNA methylation analysis of 13 genes can be a useful
assessing tumour mutational profile aimed to the delivery of effective non-invasive method to identify surgically treated OSCC patients at risk
targeted therapies. In Oral Squamous cell carcinoma (OSCC), ITH has of developing a second neoplasia.
been reported both in tumour cells and in related adjacent mucosa. The
presence of genetic heterogeneity in the adjacent mucosa can be This study was supported by the academic grant "Proof of Concept
interpreted as evidence of the field cancerization phenomenon (field het- d'Ateneo" from University of Bologna
erogeneity, FH). Aim of this study was to investigate the clinical impact
of ITH and FH on loco regional control.
Methods: Ten OSCC patients who received radical surgery and staged OFP-06-009
T2-T4 (5 recurrent and 5 non-recurrent) were enrolled in this study. Integrated genomics of olfactory neuroblastoma: pathologic and
Multiple areas were sampled from the bulk of the tumour and the adjacent therapeutic implications
non-neoplastic mucosa. NGS mutational analysis of 10 OSCC driver M. Classe1, H. Yao2, X. Su2, C. Creighton3, A. Burgess4, R. Mouawad5,
genes were investigated and used to calculate ITH and FH among differ- M. Wassef6, X. Leroy7, B. Verillaud4, G. Mortuaire7, F. Bielle4, D.
ent area of the tumour. Khayat8, G. Malouf9
1
Results: Mutational analysis highlighted that a single sample is often Institut Gustave Roussy, France, 2 MD Anderson, USA, 3 Baylor
scarcely accurate in assessing genetic profiles of tumours. High values College of Medicine, USA, 4 Assistance Publique Hôpitaux de Paris,
of ITH were found in both groups with a tendency to be higher in recur- France, 5 Leo Pharma, France, 6 Bichat Hospital, APHP, France,
7
rent OSCC (p=0,095). Interestingly, the FH was found significantly lower Centre Hospitalier Règional et Universitaire de Lille, France,
8
in the non-recurrent OSCC group (p=0,032). Clinique Bizet, France, 9 Hôpitaux Universitaire de Strasbourg, France
 Virchows Arch

Background & Objectives: Olfactory neuroblastomas (ONBs) are rare OFP-06-011

tumours arising in the skull base. Classification tools are poor, notably, no Evaluation of programmed death ligand-1 expression and efficacy
molecular classification of ONB has been reported. Literature data about outcomes in patients with squamous cell carcinoma of the head and
their cell of origin, the existence of molecular therapeutic targets or their neck from KEYNOTE-040 using two scoring techniques
immune environment being scarce, the biology of these tumours is still K. Emancipator1, L. Huang1, J. Juco1, D. Aurora-Garg1, T. Bal1, E.E.W.
poorly understood. Cohen2, K. Harrington3, D. Soulières4, C. Le Tourneau5, L. Licitra6, B.
Methods: Using a well described series of 59 ONBs coming from 4 Burtness7, R. Swaby1
1
different centers, we performed a multiomics analysis based on exome, Merck & Co., Inc., USA, 2 Moores Cancer Center, UC San Diego
transcriptome and methylome analysis, but also on histopathological and Health, USA, 3 The Institute of Cancer Research/The Royal Marsden
immune characteristics. NHS Foundation Trust National Institute of Health Research
Results: We highlighted 2 sub-types of ONB. The neural type is a well Biomedical Research Centre, United Kingdom, 4 Centre Hospitalier de
differentiated, poorly aggressive tumour showing neurons characteristics l'Universitè de Montrèal, Canada, 5 Institut Curie, Paris and Saint-Cloud,
and sharing phenotypic similarities with olfactory neuron progenitors. INSERM U900 Research Unit, France, 6 Fondazione IRCCS Istituto
The basal type is a less differentiated tumour, displaying an aggressive Nazionale dei Tumouri and University of Milan, Italy, 7 Yale University
phenotype, with embryonic phenotypical characteristics, sharing similar- School of Medicine and Yale Cancer Center, USA
ities with basal renewing cells of the olfactory epithelium. We showed
that the mutational load was higher in basal tumours, with notably recur- Background & Objectives: Tumour proportion score (TPS) is used to
rent IDH2 R172 mutations associated with a CpG Island Methylator measure programmed death ligand 1 (PD-L1) expression in tumour cells,
Phenotype (CIMP). whereas combined positive score (CPS) measures PD-L1 in tumour and
Conclusion: This work is the first attempt to generate a comprehensive immune cells. A post hoc analysis from the open-label, phase 3
molecular classification of ONBs using a multiomics analysis. It paves KEYNOTE-040 (NCT02252042) trial was performed to determine
the way towards a new molecular classification which will allow a better whether CPS is a suitable alternative for TPS in patients with head and
stratification of patients and will open the field of new therapeutic strat- neck squamous cell carcinoma (HNSCC) under evaluation for second-
egies for this rare tumour. line therapy.
Methods: Patients with platinum-refractory HNSCC received
pembrolizumab (200 mg Q3W) or chemotherapy/biotherapy.
OFP-06-010 Pathologists scored tumour samples for TPS and CPS using the PD-L1
Clinicopathological characterisation and outcomes analysis of a IHC 22C3 PharmDx assay. Scoring methods were compared based on
single-institutional cohort of early-stage oral tongue squamous cell objective response rate (ORR; RECIST v1.1), overall survival (OS), and
carcinoma treated by surgery alone progression-free survival (PFS). Cutoffs were evaluated by receiver op-
J. Filipe1, M. Labareda2, S. Esteves3, E. Netto2 and I. Fonseca1,4 erating characteristic (ROC) analysis using ORR.
1
Serviço de Anatomia Patológica, Instituto Português de Oncologia de Results: PD-L1 expression was evaluated in 475/495 enrolled patients.
Lisboa Francisco Gentil, Lisbon, Portugal, 2 Serviço de Radioterapia, ORR for pembrolizumab versus chemotherapy was 26.2% versus 8.5%
Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, (TPS ≥50%), 28.1% versus 7.7% (CPS ≥50), 10.6% versus 11.6% (TPS
Portugal, 3 Unidade de Investigação Clínica, Instituto Português de <50%), and 10.0% versus 12.0% (CPS <50). OS and PFS curves showed
Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal, 4 Instituto de congruence between corresponding groups by TPS and CPS, better sur-
Anatomia Patológica, Faculdade de Medicina, Universidade de Lisbon, vival in the pembrolizumab versus chemotherapy arm in the PD-L1high
Portugal group, and similar survival in the PD-L1low group. ROC analyses con-
firmed that appropriate cutoffs occurred at TPS 50% and CPS 50.
Background & Objectives: Early-stage oral tongue squamous cell car- Conclusion: CPS 50 can be used interchangeably with TPS 50% to
cinoma (OTSCC) prognosis and treatment remain controversial. The aim determine PD-L1 status in patients with HNSCC undergoing evaluation
of this study was to assess the impact of clinicopathological features in for second-line treatment. Data from the ROC analyses further suggest
outcomes of a cohort of patients with early-stage OTSCC treated by that CPS may be more sensitive than TPS at lower cutpoints (CPS ≥1).
surgery only.
Methods: A retrospective analysis of 71 cases of early-stage OTSCC Funding for this research was provided by Merck Sharp & Dohme Corp.,
treated by surgery only at our Institution between 2006 and 2010, staged a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
as pT≤2N0 at time of treatment (AJCC, 7thed) was performed. Tumour
thickness, depth of invasion (DOI), histologic grade, margins,
lymphovascular invasion (LI), perineural invasion (PI), worst pattern of OFP-06-012
invasion (WPOI) and lymph node dissections, when performed, were re- Surgical follow-up of ThyroSeq® positive thyroid nodules: the
evaluated. Kaplan-Meier method was used for recurrence-free survival Memorial Sloan Kettering Cancer Center experience
(RFS) and disease-specific survival (DSS) analysis; log-rank test was D. Buonocore1, O. Lin1, J. Cohen1
1
performed for subgroup comparison. Memorial Sloan Kettering Cancer Center, USA
Results: Median age was 62years and median follow-up of 6.3years.
66% of the tumours were pT1. Lymph node dissection was performed Background & Objectives: The current American Thyroid Association
in 44% of the patients. 3 cases had tumour DOI>10mm, and were re- guidelines suggest the use of molecular studies in the management of
staged to pT3 (AJCC, 8thed). Surgical margins were positive or ≤1mm in patients with an indeterminate cytology diagnosis. ThyroSeq®, one of
14%. PI was present in 6% and LI in 3%. All cases had WPOI<5. The 5- the most used thyroid molecular tests in the U.S., has been reported to
year DSS and RFS rates were 86% and 64%, respectively. DOI ≥5mm have high positive predictive value(PPV). We propose to evaluate the
was associated with poorer DSS (p=0.006). PI correlated with recurrence PPV of ThyroSeq® at a major cancer center in the U.S. in which the
and with lower DSS (p=0.006 and p<0.001, respectively). prevalence of malignancy is high.
Conclusion: In our cohort of patients, 4% of T2 OTSCC were upstaged Methods: Cytology material from 252 thyroid nodules diagnosed as inde-
after pathological characterization using the 8th AJCC staging system. terminate were submitted for ThyroSeq® analysis. The results were reported
Tumour DOI≥5 mm and the presence of PI correlated with poorer as positive in 94 cases. Sixty-one of these 94 cases were surgically resected.
prognosis. The ThyroSeq® results were correlated with the surgical diagnosis.
Virchows Arch

Results: Fourteen of the 62 nodules were benign on resection including; Background & Objectives: Melanocytic nevi are common, benign,
5 nodular hyperplasia, 5 Hashimoto’s thyroiditis, 2 follicular adenomas, pigmented skin tumours formed by proliferation of melanocytes which
and 4 oncocytomas. Additionally, there were 9 noninvasive follicular may present a number of unusual features, such as the vascular affinity of
thyroid neoplasm with papillary-like nuclear features (NIFTP), a tumour nevus cells and its consequences. This study aims to highlight the asso-
with unclear malignant potential. NRAS was the most commonly detect- ciated intravascular pseudoemboli and nevus cell protrusion in benign
ed mutation in the benign nodules, it was present in 6 of the 16 nodules intradermal nevi.
and 4 of 9 NIFTPs. NRAS was also the most common mutation detected Methods: We have reviewed a total of 1154 compound and intradermal
in malignant lesions, being present in 15 of 36 cases while BRAFV600E melanocytic nevi diagnosed between 2017-2018 in our department and
was detected in only 4 cases. have selected 78 (6.75%) cases with intravascular nevus cell protrusion
Conclusion: In our experience the ThyroSeq® PPV was 73.8% and falls (IVNP) and 2 (0.17%) cases with intravascular nevus cell aggregates
to 59.0% when NIFTP is excluded. The most common mutation in be- (IVNcA); immunohistochemistry for S100, CD34 and D2-40
nign and malignant lesions was NRAS (25/61). (podoplanin) was performed.
Results: The IVNcA and IVNP lesions were mostly located on the torso
(58.75%), followed by the head and neck region (30%) and the limbs
Monday, 9 September 2019, 17:15 - 19:15, Thalie (1.25%); 8 cases had no clinical records regarding the location (10%).
OFP-07 | Dermatopathology Female-to-male ratio was 2.5:1, with a median age of 32 years (between
16-80 years). The maximum diameter ranged from 0.2 cm to 2.3 cm
(median 0.7 cm); median tumour thickness: 0.31 cm. IVNPs were
OFP-07-001
tipically situated in the upper/mid dermis and IVNcAs were identified
Assessment of circulating tumour cells and circulating cell-free DNA
in the upper dermis. In all cases intravascular protruding tumour cells
in patients with metastatic melanoma
were covered by CD34/D2-40 positive cells (endothelial cells).
M. Badrignans1, B. Tournier2, G. Jeudy3, S. Dalac3, C. Chapusot2, L.
Conclusion: This is the largest study that evaluates morphologically and
Martin1,2,4, M. Aubriot-Lorton1,2
1 immunohistochemically the presence of IVNPs and IVNcAs within be-
Service de Pathologie, CHU Dijon, France, 2 Plateforme de Gènètique
nign melanocytic nevi. Our results describe the demographic characteris-
des Cancers solides et des Hèmopathies malignes, CHU Dijon, France,
3 tics of patients with IVNPs and IVNcAs within common melanocytic
Service de Dermatologie, CHU Dijon, France, 4 Unitè d'innovation en
nevi, creating the premises for further studies.
Gènètique et Epigènètique des cancers, CHU Dijon, France
This work was supported by a grant of Romanian-Ministry-of-Research-
Background & Objectives: Circulating tumour cells (CTCs) and cell-
and-Innovation, CCCDI-UEFISCDI, project number 61PCCDI/2018PN-
free DNA (ctDNA) released by tumours in the blood, could be useful as
III-P1-1.2-PCCDI-2017-0341.
non-invasive biomarkers of patients with metastatic melanoma. Our pro-
spective study evaluates the feasibility of an isolation device of CTCs
(ScreenCell®), and determines if the variation of CTCs and ctDNA are
OFP-07-003
correlated with therapeutic efficacy.
Effective treatment of Merkel cell carcinoma cell lines by the com-
Methods: Five patients were included before they received the first
bined inhibition of BCL-2 and PI3Ka
line of treatment. Every three months, they had clinical and radio-
E. Chteinberg1, W. Gerritsen1, E. Speel1, V. Winnepenninckx1, A.K.
logical evaluations, and peripheral blood tests (CTCs and ctDNA).
Kurz2, M. Zenke2, A. zur Hausen1
CTCs were isolated according to the manufacturer instructions and 1
Maastricht University Medical Centre+, The Netherlandsk, 2 University
counted by two observers (MB, MHA). ctDNA were isolated with
Hospital RWTH Aachen, Germany
QIASymphony Circulating DNAkit. BRAF mutations were detect-
ed by ddPCR.
Background & Objectives: Merkel cell carcinoma (MCC) is a highly
Results: Among the 5 melanoma, only one had a BRAF mutation. The
malignant skin cancer of unknown cellular origin. MCC is characterised
inter-observer's (R²=0.98) and intra-observer's (R²=0.99) correlation for
by a typical trilinear differentiation: epithelial, neuroendocrine, early B-
CTCs were excellent. Cytological criteria of malignancy were easily rec-
lymphoid. In addition, MCCs highly express BCL-2 and PI3Kα on the
ognizable, with only 0.76±0.6 "uncertain malignant cell" (UMC) per
protein level.
filtration. The negative sample contains 0.67±0.58 UMC / filtration.
Specific inhibition of BCL-2 and PI3Kα has been introduced in the treat-
During patient follow up, the evolution of CTCs and radiological tumour
ment of some non-Hodgkin lymphomas and leukemias. We tested the
burden were similar. ctDNA and CTC's variations were similar in the case
combined inhibition of BCL-2 and PI3Kα in MCC cell carcinoma lines
with BRAF mutation. Otherwise, ctDNA had only slight variations but
(MCCcls).
without relapse.
Methods: Four MCCcls (MKL-1, MKL-2, WaGa and MCC13) and one
Conclusion: ScreenCell® is a reliable, reproductive and non-invasive
B-acute lymphoblastic cell line REH, all previously shown to express
test for CTCs isolation in routine. CTCs are more informative than
PI3Kα and -except MCC13- BCL-2, were treated with different concen-
ctDNA, for the follow up of melanoma especially when BRAF is not
trations of the BCL-2 inhibitor Navitoclax for 72h. Cell viability was
mutated. CTCs variations seem to appear earlier than tumour's growth,
assessed by the XTT assay (ThermoFisher), IC50 were determined, and
but clinical studies are needed to prove that CTCs can detect relapse
cleaved PARP detection by Western-blotting was used as read-out for the
before imagery.
induction of apoptosis. The combined effects of Navitoclax and the
PI3Kα inhibitor (Byl719) were analysed. The p-values were calculated
by a One-Way ANOVA.
OFP-07-002
Results: Navitoclax treatment alone effectively decreased the viability of
Intravascular nevus cell protrusion and aggregates in otherwise com-
all cell lines except MCC13. Increased cleaved PARP levels following
mon melanocytic nevi
increasing concentrations of Navitoclax treatment revealed that its effects
G. Tudor1, O. Stefan1, V. Nica1, R. Tanasa1, V. Chitu1,2, C. Caruntu2, C.
indeed was mediated by apoptosis. IC50 values of MCCcls were 2 to 10
Popp1, M. Cioplea1, S.A. Zurac1,2
1 times higher compared to REH. The combination of Navitoclax and
Colentina Clinical Hospital, Romania, 2 Carol Davila University of
Byl719 revealed a significant (p< 0.05) synergistic effect in all cell lines
Medicine and Pharmacy, Romania
except MCC13.
 Virchows Arch

Conclusion: Our results point to a novel and important therapeutic option laboratories and the evaluation by the team of referent pathologists was
using a combination treatment of Navitoclax and Byl719 in stage III/IV communicated to the laboratories.
MCC patients primarily or secondarily not responding to immunotherapy. Results: The majority (80%) of the laboratories used the 22C3 clone in an
in house assay. Approximately 60% have a Ventana Benchmark appara-
tus at their disposal. The most challenging cases were those around the
OFP-07-004 5% cut-off (based on the CheckMate 067 study at that time). High amount
E-cadherin and N-cadherin expression pattern in common of melanin resulted in a systematic overestimation of the PD-L1 expres-
melanocytic nevi sion. The overall interlaboratory concordance was 65%. The use of dif-
O. Stefan1, G. Tudor1, C. Constantinescu1, C. Luca1, D. Boda2, C. ferent clones, platforms, protocols and detection kits didn´t have played
Caruntu2, M. Cioplea1, L. Nichita1,2, S.A. Zurac1,2 an important role in the scoring.
1
Colentina Clinical Hospital, Romania, 2 Carol Davila University of Conclusion: Independent of different platforms and clones, PD-L1
Medicine and Pharmacy, Romania stainings resulted in similar conclusions in about 65% of cases.
Abountant melanin deposition causes overestimation.
Background & Objectives: Cadherins constitute a family of transmem-
brane glycoproteins that mediate cell-to-cell adhesion and play an impor-
tant role in the maintenace of normal tissue architecture. Our study aims OFP-07-006
to evaluate the role of E-cadherin and N-cadherin in the pathogenesis of Imbalance between types I and VI collagen promotes skin fragility in
intravascular nevus cell protrusion (IVNP) and intravascular nevus cell human and experimental diabetes
aggregates (IVNcA) within common melanocytic nevi (CMN). J.T. De Miranda1, V.P. Toledo1,2, Z.A. Queiroz1, L.K. Ramos da
Methods: We have selected a study group including 30 CMN with IVNP Silveira1,2, A. dos Santos Filho3,2, A.P. Pereira Velosa3, S. Catanozi1,4,
and IVNcA and a control group that comprised 30 CMN without IVNP and V.l. Capelozzi1,5, W. Rosolia Teodoro1,2
1
IVNcA, matched individually by age, sex and anatomical location of the Faculdade de Medicina, Universidade de Sao Paulo, Brazil,
2
lesion. We assesed immunohistochemically the expression of E-cadherin Rheumatology Division, Brazil, 3 Hospital das Clinicas HCFMUSP,
and N-cadherin within both groups, followed by calculating the odds-ratio Faculdade de Medicina, Universidade de Sao Paulo, Brazil,
4
(OR) and assessing the p-value using the Fisher's exact test. Department of Endocrinology, Brazil, 5 Department of Pathology, Brazil
Results: The glycoproteins had 7 patterns of expression in both study and
control groups: superficial, deep, superficial&deep, superficial>deep, Background & Objectives: One third of people with diabetes develop
deep>superficial, patchy and no expression. skin complications from the long-term effects of the hyperglycemia on
For E-cadherin we identified a tendency towards deep pattern of expres- the microcirculation and on skin collagen. Previous works have demon-
sion in IVNP and IVNcA nevi comparing with superficial and strated significant imbalance between collagen fibers in diabetic skin.
superficial&deep patterns in CMNs (OR=3.5; p=0.037). This study aimed to compare the expression of the fibrillary Type I col-
For N-cadherin no statistical significant differences in expression patterns lagen (Col I) and the anchorage Type VI collagen (Col VI) on skin from
were present (OR=0.3; p=0.084). human and experimental diabetes.
Conclusion: Melanocytic lesions with IVNP and IVNcAs depict certain Methods: Diabetes was induced in Wistar male rats by streptozotocin
E-cadherin expression patterns more frequently than CMN without IVNP inoculation. The animals were euthanized at 7 (n=10, DG7d) and 30 days
and IVNcAs, but its role in the pathogenesis of the vascular affinity of (n=10, DG30d). Matched control group was inoculated with saline
melanocytes is still to be debated. (n=10; CG7d; n=10, CG30d). Skin biopsies were obtained from patients
with diabetes (n=5) with high serum glucose levels and from heath indi-
This work was supported by a grant of Romanian-Ministry-of-Research- viduals (n=4). We used immunofluorescence and histomorphometry to
and-Innovation, CCCDI-UEFISCDI, project number 61PCCDI/2018PN- evaluate Col I and Col VI fibers in skin biopsies
III-P1-1.2-PCCDI-2017-0341. Results: Skin from DG7d and DG30d diabetic rats showed a dermal fibro-
sis thus resulting in abnormal and significant increased deposition of the
Col VI fibers and decreased deposition of Col I when compared to controls
OFP-07-005 (p<0.0001). Human diabetic skin biopsies also showed a dermal fibrosis
A PD-L1 IHC 28-8 PharmDX ring trial on metastatic melanoma: histologic pattern and so demonstrated comparable abnormal and increased
practical aspects deposition of Col VI (17.99±0.98 vs 5.01±0.21; p<0.0001) and decreased
V. Siozopoulou 1 , K. De Winne 1 , E. Smits 2,3 , J. Jacobs 1,2 , K. Col I (2.55±1.0 vs 18.78±2.46, p<0.0001) when compared to control.
Zwaenepoel1,2, P. Pauwels4 Conclusion: We concluded that an in situ imbalance between Col VI and
1
Department of Pathology, Antwerp University Hospital, Belgium, Col I modulates skin fibrosis in human and experimental diabetes emerg-
2
Center for Oncological Research, University of Antwerp, Belgium, ing as a promising therapeutic option for recovering skin fragility.
3
Center for Cell Therapy and Regenerative Medicine, Antwerp
University Hospital, Belgium, 4 Laboratory of Pathological Anatomy, Supported by Fapesp, Capes, LIM.
Antwerp University Hospital, Edegem, Belgium

Background & Objectives: A Belgian ring trial for PD-L1 IHC staining OFP-07-007
in melanoma was organized by the pathology department of Antwerp Melanomas with spindle cell differentiation: a review of clinical,
University Hospital. pathological and molecular characteristics
Methods: The trial went on from December 2017 until July 2018 and a M. Gonzalez Farre1, S. Tormo Mainar2, E. Andrades López3, J. Lloreta
total of 14 different laboratories participated. One site participated with Trull1, B. Espinet Solà1, B. Bellosillo Paricio1, A. Torner Calvo1, R.M.
two different protocols.The first and last slides of 6 selected melanoma Pujol Vallverdu2, B. Lloveras Rubio1,4,5, S. Segura Tigell2, C. Barranco
cases were stained with PD-L1, using PD-L1 28-8 pharmDX kit of Sanz1
1
Agilent on an Autostainer Link 48 platform. Each participating laboratory Pathology Department, Hospital del Mar, Barcelona, Spain,
2
received 2 unstained slides and was asked to return 1 PD-L1 stained slide Dermatology Department, Hospital del Mar, Spain, 3 Institut Hospital
per case and to report the used protocol and their given PD-L1 score. The del Mar d'Inverstigacions Mèdiques (IMIM), Spain, 4 Universidad
stained slides were evaluated by a team of 2 experienced pathologists. Autónoma de Barcelona, Spain, 5 Institut Hospital del Mar
Comparison of the evaluation by the pathologists of the different d'Investigacions Mèdiques, Spain
Virchows Arch

Background & Objectives: Melanomas with spindle cell differentiation OFP-07-009

can be difficult to diagnose both clinically and histologically. A retrospec- A 5-year retrospective analysis of all cutaneous metastases from a
tive review of the clinical and pathological characteristics, the immuno- single dermatopathology unit
histochemical (IHC) and molecular profiles of a series of melanomas with A.C. Lisievici1, T.A. Georgescu2, M. Leventer3, G. Dodan3, T. Tebeica4
1
spindle cell differentiation was performed. Carol Davila University of Medicine and Pharmacy, Bucharest,
Methods: Ten skin biopsies with a predominantly fusocellular pattern Romania, 2 Department of Pathology, Bucharest Emergency University
were selected from the melanoma’s record of our hospital. Hospital, Romania, 3 Department of Dermatovenerology, Dr. Leventer
Immunohistochemical techniques (MelanA, HMB45, S100 and Centre, Bucharest, Romania, 4 Department of Pathology, Dr. Leventer
SOX10), ultrastructural studies (6 cases), FISH techniques (RREB1, Centre, Bucharest, Romania
MYB, CEP6, CCND1 probes) and BRAF (V600E) mutation through
Sanger sequencing (6 cases) and Idylla system (4 cases) were done. Background & Objectives: Cutaneous metastases are uncommon le-
Results: Ten patients (8 men and 2 women) with an average age of 78 sions associated with poor prognosis, which sometimes embody the first
years were included in the study. Four patients presented multiple loco- presentation of malignancy. Some autopsy studies revealed that approx-
regional relapse, 2 distant metastases and 5 died. The lesions showed a imately 2% of those with visceral cancer had cutaneous metastases, while
spindle cell proliferation of predominantly dermal location. The medium other series observed that the skin represents the 18th most frequent met-
Breslow Index (BI) was 6.55mm and the mitotic index 4.55/mm2. All astatic site involved by all tumours. Moreover, the diagnosis may not
cases expressed S100 and SOX10 but only five were immunoreactive for always be at hand for the practicing pathologist, considering that the
MelanA and HMB45. Ultrastructural study identified aberrant melano- clinical aspects are often misleading.
somes in 5 of 6 cases. Molecular studies demonstrated a BRAF mutation Methods: This is a retrospective study including 44 cases of cutaneous
in 2 of 10 evaluable cases. metastasis that were diagnosed in our Dermatopathology unit, during a
Conclusion: Fusocellular melanomas are a distinctive clinicopathologic period of five years (2015-2019). We thoroughly re-examined the
subtype that may pose important diagnostic challenges to both clinicians Hematoxylin-Eosin and immunohistochemically stained slides, aiming
and pathologists. They show high proliferative activity, locoregional ag- to establish clinico-pathological correlations. A median of 7 immunohis-
gressiveness and elevated mortality rates. Immunohistochemically, com- tochemical markers were used in order to come to the final diagnosis.
mon melanocytic markers (MelanA and HMB45) are frequently negative, More than half all cases had clinical aspects suggestive for metastasis and
whereas SOX10 is very helpful in this setting. BRAF mutation is often 53% had no history of neoplastic disease.
negative. Results: 82% presented as nodules, 16% mimicked an inflammatory lesion
and 2% presented as neoplastic alopecia. Median age was 61 years (24-86
years) and 69.7% were females. Breast carcinoma was the most frequent
OFP-07-008 primary tumour (n=16), followed by melanoma (n=13), gastrointestinal tract
YAP1 expression in Merkel Cell Carcinoma adenocarcinoma (n=6), squamous carcinomas (n=4), and pulmonary carci-
A. Sykaras 1 , G. Kyriakopoulos 1 , G. Kazamias 1 , C. Stamou 1 , S. noma (n=2). Tumour emboli were noticed in 27%, ulceration of the epider-
Pantelakos1, P. Dolkiras1, C. Kouvidou1 mis only in 18% and epidermotropism in 20%. Of all melanoma metastases,
1
Department of Pathology, Evangelismos General Hospital, Athens, 58% were distant, while the rest represented in-transit metastases.
Greece Conclusion: Cases clinically presenting as inflammatory lesions (plaque,
eczema) correlated best with breast origin. Vascular invasion was also
Background & Objectives: The transcriptional co-activator Yes-associ- most frequently encountered in this type of carcinoma. Metastases located
ated protein (YAP1) is a critical downstream effector of the Hippo signal- on the abdomen correlated with the gastrointestinal origin of the tumour,
ing pathway that controls organogenesis and tumourigenesis. YAP1 is with the exception of one case of metastatic high-grade serous carcinoma
implicated in many cancers and acts as oncogene or tumour suppressor of the ovary, which presented as sister Mary Joseph nodules.
gene, depending on cancer type. In particular, expression of YAP1 is
upregulated in Basal Cell Carcinoma (BCC) and Squamous Cell
Carcinoma (SCC) of the skin whereas YAP1 expression is lost in high- OFP-07-010
grade neuroendocrine tumours of the lung, especially small cell lung Hypopigmented parasoriasis en plaque; an ignored variant
carcinoma (SCLC). Our aim is to evaluate YAP1 expression in Merkel R. Abdel Hay1
1
Cell Carcinoma (MCC), a high-grade neuroendocrine carcinoma of the Cairo University, Faculty of Medicine, Egypt
skin.
Methods: We performed immunohistochemistry using a monoclonal Background & Objectives: Parapsoriasis en plaque (PSEP) is a chronic
anti-human YAP1 antibody on formalin-fixed paraffin embedded dermatosis whose biological distinction from early mycosis fungoides
(FFPE) sections of five MCC tumour specimens. The specimens included (MF) is still not clearly defined. Our aim was to verify whether an un-
two primary MCC (one Merkel Cell Polyoma Virus-MCPyV positive and common hypopigmented disorder sharing many mutual features with
one MCPyV negative) and three metastatic MCC to lymph nodes (two should be considered as a hypopigmented variant.
MCPyV positive and one MCPyV negative). We used sections of two Methods: 50 patients presenting with this unusual hypopigmented disor-
BCC and two SCC specimens as external positive controls. der were included. Patients were subjected to proper history taking, gen-
Results: YAP1 expression was completely abolished in all MCC speci- eral and dermatological examination, laboratory investigations, histopath-
mens. In agreement with the literature, there was aberrant expression of ological examination and IHC staining to exclude differential diagnoses
YAP1 (strong nuclear and faint diffuse cytoplasmic stain) in BCC and of hypopigmented lesions.
SCC specimens. Results: All other disorders had been excluded. Clinically, the lesions
Conclusion: Our preliminary results suggest that YAP1 expression is lost were comparable to those of classic small-plaque parapsoriasis with
in MCC. This finding is in line with the concept that YAP1 is lost in high- digitiform extensions of most the lesions. Histopathologically, there was
grade neuroendocrine tumours and may suggest that YAP1 has a tumour mild epidermal hyperplasia, reduced basal pigmentation, and decreased
suppressor function in the context of MCC development. We are currently number of melanocytes at the base of the epidermis. Focal parakeratosis,
expanding our analysis to a large cohort of MCC specimens, trying to foci of mild spongiosis, and focal exocytosis were encountered in the
validate our preliminary data and correlate the YAP1 expression pattern 94% of cases. The dermis showed scanty superficial perivascular infiltrate
with the presence of MCPyV and the expression of other neuroendocrine of lymphocytes and histiocytes with frequent extension into the papillary
markers. dermis. No interface changes or atypical lymphoid cells. IHC staining
 Virchows Arch

showed CD3 immunopositivity. CD8+ T cells predominance over CD4+ median level of infiltration (hereinafter referred to as CD8-high)
T cells was reported in 88% of cases. displayed high expression levels of immune-related cytokines, immuno-
Conclusion: Based on our findings we deliberate this hypopigmented therapy response markers, MHC-I expression, and infiltration by PD-L1-,
disorder as a variant of the PSEP family with all features of PSEP and PD-1- and LAG-3-expressing immune cells. The multivariate analysis
thus could be mentioned as hypopigmented PSEP. revealed that CD8-high group highly expressed CD74, LYZ and HLA-
B while the CD8-low cases overexpressed CXCL14. In addition, M2
tumour-associated macrophages (TAMs) were localized at the tumour
OFP-07-011 invasion front.
The role of CD123 positive plasmacytoid dendritic cells in cutaneous Conclusion: We provide the first comprehensive immune-phenotype
lupus erythematosus profiling of PDS. These results will aid in further assessment of PDS
N. Roy1, G. Gupta1, R. Ramakrishnan2 cases and formulate the qualification criteria for immunotherapy in indi-
1
Imperial College Healthcare NHS Trust, United Kingdom, 2 North West viduals presenting with advanced stages of this rare skin malignancy.
London Pathology, United Kingdom

Background & Objectives: Cutaneous lupus erythematosus(CLE) dem- Monday, 9 September 2019, 17:15 - 19:15, Galliéni 5
onstrates clustering of CD123 positive plasmacytoid dendritic cells OFP-08 | Joint Session: Neuropathology / Ophthalmic
(PDC) that has diagnostic utility. Our study aims to identify diagnostic Pathology
& prognostic value of CD123 positive PDC in CLE.
Methods: CLE diagnosed between 2013 & 2017 were reviewed with respect
to histology & immunofluorescence (IMF). Immunohistochemistry (IHC) to
CD123 was performed & semi-quantitative criteria were developed for OFP-08-001
assessing staining intensity & patterns of distribution. Deregulated expression of imprinted DLK1-DIO3 region in glioblas-
Results: 72/81(88%) cases stained for CD123, 45(55%) strong & toma stem-like cells: tumour suppressor role of lncRNA MEG3
27(33%) weak. Predominant distribution was perivascular 56/72 (90%) M. Martini1, L. Ricci-Vitiani2, G. Marziali2, M. Bucciarelli2, V. Lulli2,
with perifollicular in 39/72 (54%). Proportion of cells stained was 3+ in Q.G. D'Alessandris3, R. Pallini4
1
26/45(57%) & 2+ in 18/45 (40%) with strong staining while mostly 1+ Institute of Pathology, Rome, Italy, 2 Department of Oncology and
cells with weak 25/27(92%). With IMF, 12/31 (38%) demonstrated IgG, Molecular Medicine, Istituto Superiore di Sanità, Italy, 3 Fondazione
& 11/31 (35%) also showed C3. 11/12 IMF positive cases also showed Policlinico Universitario A. Gemelli IRCCS, Rome, Italia, 4 Institute of
CD123 (91%) staining; 6/11 (55%) strong & 5/11 (45%) weak, thus Neurosurgery, Catholic University School of Medicine, Italy
demonstrating positive correlation with the histological diagnosis. 35/38
(92%) cases with no IMF data showed CD123 staining, again, demon- Background & Objectives: Glioblastoma (GBM) stem-like cells
strating a positive correlation with the histological diagnosis. (GSCs) are thought to be responsible for the maintenance and
Conclusion: Our study re-iterates the routine diagnostic utility of the aggressiveness of GBM, the most common primary brain tumour
CD123 demonstrating positivity in 88% of cases of CLE. It is therefore in adults. LncRNAs have emerged as important players in cancer.
a useful adjunct & of diagnostic value in distinguishing lupus from other This study aims at elucidating the involvement of deregulations
lymphoid infiltrates, particularly CTCLs. CD123 therefore should be within the imprinted DLK-DIO3 region on chromosome 14q32 in
used routinely in diagnosis of cutaneous lymphoid infiltrates. GBM pathogenesis.
Methods: RT-PCR analyses were performed on GSCs and GBM tissues.
Al results were correlated with the clinical features. Methylation analyses,
OFP-07-012 gene expression and Reverse-Phase protein Array profiles were used to
Profiling the tumour immune microenvironment in pleomorphic der- investigate the tumour suppressor function of MEG3. Statistical analysis
mal sarcomas suggests its potential effectiveness for immunotherapy was performed appropriately.
K. Noh1, S. Klein2, C. Mauch3, S. Wagener-Ryzek1, M. Schoemmel4, R. Results: Loss of expression of genes and non-coding RNA within the
Buettner5, A. Quaas2, D. Helbig3 DLK1-DIO3 locus, mediated by epigenetic silencing, was observed in
1 GSCs and GBM tissues. Kaplan-Meier analysis showed lower expression
Institute of Pathology, University Hospital Cologne, Germany,
2
Institute for Pathology, Cologne, Germany, 3 Department of of MEG3 and MEG8 lncRNAs significantly correlated with short survival in
Dermatology, University Hospital Cologne, Germany, 4 Department of GBM patients. MEG3 restoration impairs tumourigenic abilities of GSCs
Internal Medicine, University Hospital Cologne, Germany, 5 University in vitro inhibiting cell growth, migration and colony formation and decreases
Hospital Cologne, Germany in vivo tumour growth reducing infiltrative growth. These effects were as-
sociated with modulation of genes involved in cell adhesion and EMT.
Background & Objectives: Immunotherapies, with their high objective Conclusion: Our data show that MEG3 is involved in a complex network
response rates and long-lasting clinical benefits, have revolutionized can- that regulates cell adhesion, DNA damage, cell proliferation and stemness
cer treatment. Pleomorphic dermal sarcoma (PDS) is a very rare cutane- by targeting a multitude of genes. The analysis of MEG3 signatures,
ous tumour with local recurrences and distant metastases occurring in up coupled with functional in vitro and in vivo assays, identifies known as
to 28% and 20% cases, respectively. With only limited treatment options well as unexplored pathways that can be targeted with innovative therapies.
in advanced stages, there is a strong rationale to explore immunotherapies
in PDS. However, in order to achieve this, the immune microenvironment Italian Ministry of Health, (RF-2016-02361089 to LRV)
in PDS first needs to be explored.
Methods: We collected 14 PDS cases that underwent primary surgical
resection at University Hospital Cologne. With FFPE materials, we per- OFP-08-002
formed a comprehensive immune-phenotype analysis using immunohis- Ki-67 and MCM6 labelling index are correlated with overall survival
tochemistry and multiplex gene expression analysis, as well as quantita- in anaplastic oligodendroglioma, IDH1-mutant and 1p/19q
tive assessment of immune cells and immune response markers through codeleted: a multicenter study from the French POLA Network
quantitative image-analysis. C. Pouget1, S. Hergalant2, E. Lardenois1, S. Battaglia-Hsu2, H. Rèmi2, C.
Results: Eight out of fourteen PDS cases (57%) showed abundance of Carpentier3, C. Dehais4, F. Rech5, L. Taillandier6, C. Colin7, D. Figarella-
CD8-positive T-lymphocyte infiltration. Three cases that had above Branger8, G. Gauchotte1
Virchows Arch

1
Department of Pathology, CHRU, Nancy, France, 2 INSERM U1256, Methods: Sixteen (14.8%) IDH-wt GBMs were found among 108
NGERE, Facultè de Mèdecine de Nancy, Universitè de Lorraine, France, GBMs from patients aged 18-50 years diagnosed at Messina Polyclinic,
3
CRICM - UMRS975, Paris, France, 4 AP-HP, Groupe Hospitalier Pitiè- Italy, and were explored for mutations and copy number variations in 409
Salpêtrière, Service de neurologie 2-Mazarin, Paris, France, 5 Department genes, tumour mutational burden (TMB) and mutational spectrum.
of Neurosurgery, CHRU, Nancy, France, 6 Department of Neurology, Results: All 16 IDH-wt GBMs had TMB >14 mutations/Mb, and
CHRU, Nancy, France, 7 AP-HM, Hôpital de la Timone, Service 4/16 cases were ultra-mutated (TMB >100 mutations/Mb). All
d'Anatomie Pathologique et de Neuropathologie, Marseille, France ; ultra-mutated GBMs had mutational spectrum consistent with
Aix-Marseille Univ, CNRS, INP, Institut Neurophysiopathologie, DNA mismatch repair (MMR) impairment and one had also in-
Marseille, France, 8 AP-HM, Hôpital de la Timone, Service d'Anatomie crease in C>A transversions of the type associated with POLE in-
Pathologique et de Neuropathologie, Marseille, France ; Aix-Marseille activation. Accordingly, three cases had somatic mutations in MMR
Univ, CNRS, INP, Institut Neurophysiopathologie, Marseille, France genes, and one had also POLE mutation. All 4 ultra-mutated GBMs
featured at least 25% giant cells and they had significantly better
Background & Objectives: Anaplastic oligodendroglioma (AO), prognosis than non-ultramutated GBMs (P= 0.036).
IDH-mutant and 1p/19q codeleted (IDHmut+/1p19qcodel) are high Conclusion: We identified an ultra-mutated distinct subgroup among
grade gliomas. Only few prognostic markers were studied in this IDH-wt GBMs in adults <50 years that had improved prognosis and
specific histomolecular subgroup. The primary aim of this study could be recognized histologically by the presence of at least 25%
was to evaluate and compare the prognostic value of two prolif- homogenously dispersed giant cells. Since high TMB is associated with
eration markers, MCM6 and Ki-67, in a French multicenter series response to immune checkpoint inhibition, the identification of distinctive
of IDHmut+/1p19qcodel AO (POLA network), using immunohis- molecular and pathological subtype of IDH-wt GBM may have implica-
tochemistry. Further transcriptomic approaches were implemented tions for immunotherapy.
to uncover the molecular pathways associated with the overex-
pression of these markers. The study was supported by Associazione Italiana Ricerca Cancro (AIRC
Methods: Two hundred and thirty-one IDHmut+/1p19qcodel AO cases grant 5x1000 12182 to AS).
were included from the French national POLA network. MCM6 and Ki-
67 labelling index (LI) were evaluated using computer color image
analyser. Transcriptomic data were analysed in a subset of 68 microarray OFP-08-004
samples from the French POLA Network. Clinical variability in Gerstmann-Sträussler-Scheinker syndrome
Results: High MCM6 (≥ 50%) and Ki-67 (≥ 15%) LI correlated with with the P102L mutation
shorter overall survival (P=0.013 and P=0.004, respectively). A high R. Matej1, A. Tesar2, M. Smetakova1, E. Parobkova1, R. Rusina2
proliferation index, defined by MCM6 ≥ 50% and/or Ki-67 ≥ 15%, was 1
Department of Pathology and Molecular Medicine, Third Faculty of
independently correlated to a shorter survival (P=0.027; multivariate Cox Medicine, Charles University and Thomayer Hospital, Prague,
model including age, mitotic index, MCM6 and Ki-67). Transcriptomic Czech Republic, 2 Department of Neurology and Centre of Clinical
analyses revealed that while the high mRNA level of both MCM6 and Ki- Neuroscience, First Faculty of Medicine, Charles University, and
67 were positively associated with clusters enriched in gene functions like General University Hospital, Prague, Czech Republic
cell cycle progression, DNA replication, mitosis, pro-neural phenotype as
well as neurogenesis, they were negatively associated with clusters of Background & Objectives: P102L Gerstmann-Sträussler-Scheinker syn-
other functions like microglial cell activation, immune response, positive drome is a rare genetic prion disease caused by a mutation at codon 102 in
regulation of myelination, oligodendrocyte development, beta-amyloid the prion protein gene. The usual clinical presentation includes early ataxia
binding, and postsynaptic specialization. with gait disturbance, sensory symptoms in the lower extremities, and late
Conclusion: In conclusion, both MCM6 and Ki-67 LI were correlated to cognitive decline. We compared data from seven Czech patients with
overall survival. Because multivariate analyses showed that overexpres- neuropathologically confirmed Gerstmann-Sträussler-Scheinker syndrome
sion of MCM6 and/or Ki-67 was independently correlated to shorter and retrospective data from 87 published P102L cases.
survival, these two easy-to-use and costless markers could be used in Methods: We focused on gender, age of onset, duration of disease,
association in daily practice in order to predict clinical outcome. onset of dementia, presence of ataxia, duration of cognitive im-
Transcriptomics showed that IDHmut+/1p19qcodel AO are highly pro- pairment, MRI/CT abnormalities, polymorphism in codons 129
liferative tumours with upregulated pro-neural phenotype associated and 219, changes in deep tendon reflexes, and sensory symptoms.
genes, and downregulated immune response, glial differentiation, and We used descriptive statistics (the Wilcoxon-Mann-Whitney para-
myelin-related function. metric hypothesis test, principal component analysis, and Density
Based Sequential Cluster Analysis) to define typical phenotypes.
Moreover, we provided detailed neuropathological and biochemi-
OFP-08-003 cal investigations of seven Gerstmann-Sträussler-Scheinker syn-
Ultra-mutated IDH wild-type glioblastomas in patients younger than drome cases diagnosed in the Czech Republic.
50 years have peculiar histopathology and better prognosis Results: Analysis of data from our patients and from previously pub-
V. Barresi1, M. Simbolo2, A. Mafficini2, M.L. Piredda2, M. Caffo3, S.M. lished cases suggest the existence of four clinical phenotypes ("typical
Cardali3, A. Germanò3, S. Cingarlini2, C. Ghimenton4, A. Scarpa5 Gerstmann-Sträussler-Scheinker syndrome," "Gerstmann-Sträussler-
1
Department of Diagnostics and Public Health, Section of Anatomical Scheinker syndrome with areflexia and paresthesia," "pure dementia
Pathology, University and Hospital Trust of Verona, Italy, 2 University of Gerstmann-Sträussler-Scheinker syndrome," and "Creutzfeldt-Jakob
Verona, Italy, 3 University of Messina, Italy, 4 Hospital Trust of Verona, disease-like Gerstmann-Sträussler-Scheinker syndrome") each with dis-
Italy, 5 Department of Diagnostics and Public Health, Section of tinct disease duration and clinical manifestation, irrespective of similar
Anatomical Pathology and ARC-Net Research Center, University and neuropathological changes and biochemical properties of the pathological
Hospital Trust of Verona, Italy prion protein. Our analysis also suggests that Gerstmann-Sträussler-
Scheinker syndrome is probably far more common than previously
Background & Objectives: Glioblastomas (GBM) are classified into estimated.
IDH-mutant and IDH-wild type (IDH-wt). The latter are rare in adults Conclusion: Gerstmann-Sträussler-Scheinker syndrome is a rare genetic
<50 years. This study aimed at identifying the mutational asset of IDH- prion disease with higher prevalence than previously estimated, and de-
wt GBMs in patients aged 18-50 years for which limited data is available. spite its clinical variability and similarities in neuropathological and
 Virchows Arch

biochemical investigations, four different phenotypical subgroups can be molecularly, was carried out in the period between 2009 and 2016. A
identified. quantitative determination of the MGMT methylation status was made
by pyrosequencing from macrodissected FFPE samples. In all cases the
Ministry of Health (Conceptual Development of Research Organization percentage of tumour cells in the macrodissected sample was >40%. Four
VFN64165, General University Hospital, DZ1716, Thomayer Hospital highly discriminating methylated/non-methylated CpG islands were test-
TN64190, Grant Agency of the Ministry of Health (AZV ed. The final result was obtained by averaging the methylation percentage
NV18_04_00179). of the 4 CpG islands in each case. Two approaches to data management
were evaluated, the first one considering that values of 25% and higher
methylation was the prognostic risk factor, and the second considering the
OFP-08-005 methylation factor in quartiles of their sample distribution (<5% , 5%-
Frequency of mismatch repair protein deficiency and PD-L1 in high 9.4%, 9.4-20% and >20% methylation). The results have been correlated
grade glioma in adolescent and young adults with relevant clinical and oncological parameters. A complete statistical
M. Al-Hussaini1, S. Ghnimat1, G. Almuhaisen2 study has been applied.
1
King Hussein Cancer Center, Jordan, 2 Mu'tah University, Jordan Results: Kaplan Meier analysis showed that the MGMT status
methylation was an independent prognostic factor in respect with
Background & Objectives: CNS tumours in adolescents and young adults the age, KPS and tumour resection. For a cut-off value >25% of
(AYA) are rarely reported in literature, and the association with cancer MGMT methylation the correlation with survival was especially
predisposition syndrome is not established. PD-L1 is used to predict the strong (Wilcoxon, p=0.01). The median survival of patients with
potential response of patients to immunotherapy. A link between mismatch- GBM with MGMT> 25% was 24.62 months and a 2 years overall
repair protein deficiency (MMRP-D) and response to immunotherapy is survival of 100%, while that of the group with a MGMT <25% was
established. We aim to investigate the frequency of MMRP-D in AYA with 14 months and a 2 years survival of 18%. In addition, in the quar-
high grade glioma, and any potential association with PD-L1. tiles cases the MGMT was highly significant prognostic parameter
Methods: Cases diagnosed with high grade gliomas in the age group 15- with a Log-Rank test of p=0.002 and a Wilcoxon test of p=0.001.
39 years were retrieved. Cases were stained for MLH-1, PMS2, MSH-2, The median of overall survival of patients in the first quartile with a
and MSH6, PD-L1 and P53. A total of 96 cases including 54 males MGMT <5% was 13.6 months (IC95% 8.4-15.5) and for the fourth
(56.0%) were retrieved. The median age at diagnosis was 31. 93 quartile (MGMT >20%) was 24.8 months (IC95% 21.1-30.4).
(97.0%) were in the cerebrum, including 49 (51.0%) glioblastoma. Conclusion: It is concluded that the quantification by pyrosequencing
Subtotal resection/ biopsy (n=86) was mostly performed. Radiotherapy from DNA obtained by using macrodissection of FFPE samples is a good
(n=82 cases) and chemotherapy (n=39 cases) were received. At time of procedure to evaluate the methylation status of the MGMT in GBM. The
collection of data, 49 patients were dead. MGMT methylation status constitutes a relevant independent prognostic
Results: Six cases were MMRP-D (MLH-1/ PMS-2 loss n=1, PMS-2 parameter to be applied in the routine diagnosis of GBM.
loss n=1, MSH-2/ MSH-6 loss n=1, MSH-6 loss n=3 cases). only one
case showed loss of MSH-2/ MSH-6 in both tumour and normal cells
indicating a germ line mutation (Biallelic mismatch repaid deficiency). OFP-08-007
PD-L1 was positive 23 (23.9%) cases (range, 5.0-90%). Only a single The place and prognostic value of TERT promoter mutation in mo-
case showed MMRP=D in association with positive PD-L1. 35 cases lecular classification in grade II-III glial tumours and primary
were positive for P53 stain (range from 10-90%). 18 cases were positive glioblastomas
for PD-L1 and P53. N. Kaya Terzi1, I. Yilmaz2, A.B. Oz3
1
Conclusion: Unlike our previously reported high frequency of MMRP- University of Health Sciences, Sultan Abdulhamid Han Training
deficiency in high grade gliomas in paediatrics, especially the biallalic Hospital, Istanbul, Turkey, 2 Ministry of Health Istanbul Provincial
germline mutation, MMRP-deficiency does not appear to be prevalent in Health Directorate Istanbul Sultan Abdulhamid Han Sample Training
high grade gliomas in AYA. Expression of PD-L1 in a quarter of cases and Research Hospital, Department of Pathology, Turkey, 3 University
might suggest a role of immunotherapy in high grade glioma. of Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey

Background & Objectives: Diffuse gliomas, the most common primary

OFP-08-006 malignant brain tumours, were classified by the World Health
The quantification of the methylation status of methyl-guanil-methyl- Organization as class II-IV gliomas. After 2016, in addition to the IDH,
transferase gene (MGMT) by prosequencing from macrodissected 1p / 19q and ATRX status, two mutations in the promoter region of TERT
paraffin embedded tumours is a relevant prognostic parameter in gene are frequently identified.
glioblastoma Methods: In our study, we identified 84 patients with grade II-IV glioma
M.A. Idoate 1 , P. Gómez Roca 1 , E. Benitez 1 , C. De Andrea 1 , J. with IDH, ATRX and 1p / 19q status. All tumour samples were subjected
Echeveste1, A. Arcadi1 to molecular genetic screening (Sanger sequencing for IDH and TERT
1
Pathology Department. University Hospital and School of Medicine, mutations, fluorescence in situ hybridization for 1p/19q codeletion) after
University of Navarra, Spain histological diagnosis (immunohistochemistry for IDH1 R132H, ATRX
and p53) for a more precise / molecular diagnosis. The confidence inter-
Background & Objectives: The enzyme methyl-guanyl-methyl-transfer- vals were calculated at the 95% confidence level and differences at p <
ase (MGMT) is a relevant protein that repairs the DNA that counteracts 0.05 were considered statistically significant.
the effect of temozolamide on glioblastomas (GBM). The hypermethyla- Results: Primary glioblastomas had the highest frequency of TERT pro-
tion of the promoter of the MGMT gene inactivates the tumour enzyme, moter mutations (p=0.006) followed by oligodendrogliomas (p<0.001);
which is related to a greater survival of the patients. It is postulated that astrocytomas showed the lowest frequency (p=0.107). TERT promoter
the quantification of the methylation status of MGMT could be a signif- mutations were found associated with high grade (grade III + IV) tumours
icant parameter. However, there are a few studies about quantification by when compared to lower grade (grade II) lesions (P < 0.033). TERT
pyrosequencing of tumour obtained by using macrodissection of promoter mutations were more frequent in patients older than 55 years
formalin-fixed paraffin-embedded (FFPE) samples in GBM. of age at diagnosis (P=0.023). Best overall survival was associated with
Methods: A retrospective review of the clinical and pathological charac- the presence of both TERT promoter and IDH mutations (median survival
teristics of a wide series of 60 GBM, well characterised clinically and 38.07 months), which resembles oligodendroglial progression. In
Virchows Arch

survival analysis in patients with primary glioblastomas we did not ob- Methods: Immunohistochemistry was carried out using antibodies: 1)
serve any effect of the TERT promoter mutations. Survival in gliomas 1:500 diluted sera of a previously known patient with GAE due to
with a wild TERT mutation and 1p19q codeleted (median survival 58.2 Balamuthia mandrillaris, 2) polyclonal rabbit one against Balamuthia
months) was higher than without TERT mutation and 1p19q codeletion mandrillaris and 3) polyclonal rabbit one against acanthoamoeba.
(median survival 42 months). In this study we could not reach statistical PCR using genomic DNA from FFPE sections was done for detection of
significance (P = 0.957) for survival analysis, because of the lack of the Balamuthia mandrillaris and acathoamoeba.
number of TERTp mutant cases. Results: Both cases showed extensive necrotizing granulomatous inflam-
Conclusion: Molecular classifications proposed in the literature include mation in the brain haemisphere. Histologically there were numerous
the combination of the IDH, the 1 p / 19q codeletion and the telomere amoeba trophozoites admixed with occasional cysts in brain tissue, in
maintenance mechanism as defined by alterations in TERT. To determine particular, around blood vessels. One case developed multiple skin mac-
if the TERT status provides additional prognostic information, we ules on the chest that showed panniculitis containing many amoeba tro-
analysed the relationship between overall survival in glioma patients clas- phozoite. Both immunohistochemistry and PCR confirmed the amoeba
sified according to the WHO 2016 criteria in our study. We saw that the were of Balamuthia mandrillaris.
discovery of TERTp mutations in numerous gliomas has opened the door Conclusion: An accurate diagnosis of GAE caused by Balamuthia
for a better glioma molecular classification. In the future new studies will mandrillaris is very difficult, partly because the trophozoites of
help in elucidating the value of TERT promoter mutations as biomarkers Balamuthia mandrillaris can morphologically mimic macrophages. The
in clinical practice and eventual therapeutic targets. indirect immunoperoxidase staining using the patient’s own diluted se-
rum or specific antibody was quite valuable in identifying the organisms
This study was supported by the University of Health Sciences Scientific within the lesion. PCR should serve an excellent tool for early diagnosis.
Research Unit.

OFP-08-010
OFP-08-008 Clinical significance of Ephrin receptor (Eph)-A1, -A5 and -A7 ex-
Clinicopathological characterisation of gliomas with H3-K27M mu- pression in uveal melanoma
tation: a case series M. Gajdzis1, P. Gajdzis2, S. Theocharis3, R. Kaczmarek1, P. Donizy2, P.
P. Amoroso Canão1, R. Pestana Silva1 Sarantis3, J. Klijanienko4
1 1
Centro Hospitalar Universitário de São João, Portugal Department of Ophthalmology, Wroclaw Medical University, Poland,
2
Department of Pathomorphology and Oncological Cytology, Wroclaw
Background & Objectives: Diffuse midline glioma with histone 3 Medical University, Poland, 3 First Department of Pathology, Medical
lysine-27-methionine (H3-K27M) mutation is a new entity in the 2016 School, National and Kapodistrian University of Athens, Greece,
4
WHO Classification of Tumours of the Central Nervous System. This Department of Pathology, Institut Curie, Paris, France
tumour typically occurs in a midline location and predominates in chil-
dren. Regardless of the presence of high-grade histological features, the Background & Objectives: Uveal melanoma (UM) is the most common
tumour is always assigned a WHO grade IV. In the present case series, we primary intraocular malignant tumour in adults with high metastatic po-
aimed to study the pathological features of gliomas with H3 K27M mu- tential and unfavourable prognosis. Ephrin receptors (Eph) are a subpop-
tation diagnosed at a Portuguese tertiary centre, since 2016. ulation of tyrosine kinase receptors that play important role in various
Methods: We selected all gliomas with H3 K27M mutation (2016-2018) aspects of cancer formation and progression. Moreover, Eph inhibitors
and reviewed their clinicopathological features. are currently being explored as anti-cancer agents in clinical trials. The
Results: We identified five cases of gliomas with H3 K27M mutation (3 aim of the present study was to evaluate the clinical significance of Eph-
males, 2 females). Mean age of diagnosis was 33,2 years (range: 12-45 A1, -A5 and -A7 expression in UM.
years). Four were located in the thalamus and one in the cerebellum. All Methods: Eph-A1, -A5 and -A7 protein expression was assessed
tu mo urs ha d as tro cy tic ph en ot yp e an d o n e ha d, f oca lly, immunohistochemically on paraffin-embedded tissues from 94 patients
oligodendroglioma-like features. One tumour had only low grade histo- with UM and was statistically analysed with clinicopathological features
logical features. All cases were identified using H3-K27M mutant protein as also with overall and disease-free survival.
antibody by immunohistochemistry. Despite treatment, all tumours Results: High expression of Eph-A1 was positively correlated with a
showed radiological progression and two patients died of disease. smaller tumour size (p = 0.048), absence of extrascleral extension (p =
Conclusion: Glioma with H3-K27M mutation is a heterogeneous entity, 0.030), lower mitotic activity (p = 0.042) and presence of vitreous hem-
with a wide spectrum of histological features. Immunohistochemistry orrhage (p = 0.014). High expression of Eph-A5 was associated with
using H3-K27M mutant protein antibody is an important diagnosis tool intact chromosome 3 (p < 0.001), absence of distant metastases (p =
that should be considered in tumours of the Central Nervous System 0.010) and presence of vitreous hemorrhage (p = 0.013). No relevant
arising in the midline location. associations were found for Eph-A7 expression. Survival analysis
showed that only Eph-A5 expression was associated with statistically
significant longer overall patients’ survival rate (p = 0.031).
OFP-08-009 Conclusion: High Eph-A1 and -A5 expression should be considered as
Two fatal cases of amoebic encephalitis in Japanese farmers beneficial prognostic factors in UM patients. The expression of Eph-A1, -
H. Yoon1, K. Kuroda1 A5 and -A7 in UM cells indicates their possible use as candidates for
1
Nagasaki University Hospital, Japan targeted therapy.
Background & Objectives: Balamuthia mandrillaris is the main patho-
genic protozoa causing granulomatous amoebic encephalitis (GAE),
which is a rare and progressively fatal disease. Patients with GAE present OFP-08-011
with fever, headache, nausea and vomiting, which is similar to those of Histone Deacetylase-2 expression predicts survival in uveal melano-
patients with bacterial meningitis. If patients are not diagnosed and treated ma patients
promptly with appropriate agents, they rapidly progress to death. Here we S. Theocharis1, P. Gajdzis2, G. Levidou3, D. Pouloudi1, M. Gajdzis4, P.
present two cases of Japanese farmers with GAE due to Balamuthia Donizy2, V. Milionis1, S. Albesher1, P. Korkolopoulou5, J. Klijanienko6
1
mandrillaris. Immunohistochemistry and PCR are valuable for early First Department of Pathology, Medical School, National and
diagnosis. Kapodistrian University of Athens, Greece, 2 Department of
 Virchows Arch

Pathomorphology and Oncological Cytology, Wroclaw Medical cases-25%), intensive care (32 cases-24%) and general surgery (11
University, Poland, 3 Humanpathologie Dr. Weiß GmbH, Germany, cases-8%). The autopsy diagnosis more frequent were pulmonary throm-
4
Department of Ophthalmology, Wroclaw Medical University, Poland, boembolism (24 cases-18%) and pneumonia/bronchopneumonia (16
5
1st Department of Pathology, School of Medicine, The National and cases-12%). In fourteen cases, two diagnoses were considered, being
Kapodistrian University of Athens, Greece, 6 Department of Pathology, pneumonia and bronchopneumonia diagnosis the most common. In 73
Institut Curie, Paris, France cases (54%) the clinical diagnosis was in agreement with the autopsy and,
curiously, in 38% of cases the antemortem was different from postmortem
Background & Objectives: Uveal melanoma (UM) represents the diagnosis. In 10 cases (8%) the autopsy clarified the final diagnosis.
most common primary intraocular malignancy in adults, exerting Conclusion: Our results reinforce the crucial role of clinical autopsies in
high metastatic potential and poor prognosis. Histone Deacetylases medical quality management, so it is of the utmost importance “do not let
(HDACs), through post-translational histone modifications and the clinical autopsy die”.
subsequent gene expression alterations, play a key role in carci-
nogenesis. Aim of this study was to evaluate the clinical signifi-
cance of HDAC-2 expression in UM. OFP-09-002
Methods: HDAC-2 expression [percentage and intensity of staining as Morphological and virological diagnostics of myocarditis in patients
categorical variables, and their product immunoreactivity scoring system with hypertrophic cardiomyopathy
(IRS)], classified into 4 levels: negative, mild, moderate and strong) was E. Kogan 1 , O. Blagova 1 , A. Nedostup 1 , V. Kadochnikova 2 , A.
assessed immunohistochemically in 74 UM tissue specimens and was Donnikov2, Y. Frolova3, S. Dzemeshkevich3
1
correlated-with tumours’ clinicopathological characteristics and with pa- First Moscow State Medical University (Sechenov University), Russia,
2
tients’ overall (OS) and disease free survival (DFS). DNA Technology., Moscow, Russia, 3 Russian National Surgery Centre
Results: UM patients with negative/mild nuclear HDAC-2 IRS were named after B.V.Petrovsky, Russia
older than those with moderate/strong IRS (p=0.05), whereas tumour size
significantly differed among the four levels of IRS (p=0.0132). HDAC-2 Background & Objectives: To study the morphological changes and the
nuclear and cytoplasmic IRS varied significantly among cases with dif- frequency of viral genome detection in the myocardium in patients with
ferent histological types, being higher in the epithelioid type (p=0.034 true hypertrophic cardiomyopathy (HCM).
and p=0.042 respectively). Moderate/strong HDAC-2 nuclear IRS was Methods: Study was performed on the material of biopsies (endomyocardial
more frequent in grades 2/3 and in cases with 8q chromosome gain and operative) of the heart of 15 patients (11 women and 4 men, average age
(p=0.035 and p=0.047, respectively). Increased nuclear and cytoplasmic 42.9 ± 13.3 years, from 18 to 60 years) and 1 autopsy. Serial paraffin sections
HDAC-2 IRS were correlated with favourable patients’ OS, the latter in were stained with hematoxylin and eosin, picrofuchsin , CD45 was detected
marginal terms (p=0.0415 and p=0.0846 respectively). In multivariate by immunohistochemistry (DakoCytomation). The levels of anticardial anti-
analysis HDAC-2 nuclear IRS remained significant (HR=0.309, bodies in the blood and the viral genome by PCR in myocardial tissue were
p=0.003). HDAC-2 IRS was not correlated with patients’ DFS. determined (herpes viruses 1,2,6 types, zoster, Epstein-Barr, cytomegalovi-
Conclusion: HDAC-2 expression is correlated with important clinico- rus, parvovirus B19, entero / adenoviruses).
pathological parameters and emerges as an independent, favorable prog- Results: Signs of myocarditis were found in 46.7%patients along with
nostic factor in UM patients. the changes typical for HCM (hypertrophy, degeneration, chaotic ar-
rangement of cardiomyocytes),. The viral genome in the myocardium
was detected in 73.3% of patients with true HCM (parvovirus B19, herpes
Tuesday, 10 September 2019, 08:30 - 12:00, Erato viruses type 6, Epstein-Barr and their combinations), in the blood - in
OFP-09 | Joint Session: Autopsy Pathology / Cardiovascular 33.3%, including in the blood and myocardium - in 20 %. Clinical sus-
Pathology / History of Pathology / IT in Pathology / picion of myocarditis was present in 3 patients (20%) with a combination
Pathology in Favour of Developing Countries / Other of HCM and noncompact myocardium and was confirmed morphologi-
cally in all cases. Among 12 patients without clinical suspicion of myo-
Topics
carditis, its morphological signs were detected in 33.3% of cases.
Conclusion: Myocarditis with a high frequency is detected during myo-
OFP-09-001 cardial biopsy in patients with HCM, including in the absence of clinical
Adult clinical necropsies: the gold standard of clinical practice are suspicion of it (intact systolic function), which must be considered when
decreasing worldwide. And in Coimbra? A retrospective study from prescribing treatment to patients.
2007 to 2018 comparing clinical and autopsy diagnoses
A. Lai1, M.B. Pimentão1, F. Ramalhosa1, C. Faria1, V. Almeida1, H.
Moreira1, R. Almeida1, J. Fraga1, O. Caetano1, M.A. Cipriano1 OFP-09-003
1 Canonical recognition and on-site palaeopathologic study of the
Centro Hospitalar e Universitário de Coimbra, Portugal
Blessed Vincenzo dell'Aquila (1430-1504)
Background & Objectives: Clinical autopsies still are the gold standard L. Ventura1, M. Ioannucci2, G. Tudico1, A. Raffaele3, C. Masciocchi3,4
1
of medical practice to find an accurate final diagnosis, despite the of great Division of Pathology, San Salvatore Hospital, L'Aquila, Italy, 2 Sacred
improvement of medical diagnostic procedures. Lipsanotheca, Metropolitan Archbishopry, L'Aquila, Italy, 3 Division of
In order to demonstrate the importance of clinical autopsy, a retrospec- Radiology, San Salvatore Hospital, L'Aquila, Italy, 4 Department of
tively study of 134 adults autopsies, reported during 11 years (between Radiology, University of L'Aquila, Italy
2007 and 2018), was performed.
Methods: The autopsies were classified in 3 categories: (1) clinical diag- Background & Objectives: Born to a humble family in the oldest part of
noses confirmed through the autopsy, (2) clinical and autopsy diagnosis L’Aquila (central Italy), Vincenzo worked as a shoemaker in his young
are different (3) absence of a clinical which was provided by autopsy age. In 1448, he entered the Regular Observance, a reform movement of
findings, in order to compare the clinical information with the autopsy the Franciscan Order. He received the gift of prophecy and was kept in
diagnosis. great honour by the Aragonese Kings of Naples. After death he was
Results: The majority of autopsies reported were male (79 patients or greatly honoured by local people and authorities. His body was buried
59%) and the median age was 61 years old (range 19-89 years). The three into the common grave of the friars and found intact when exhumed
departments with more autopsies requests were internal medicine (33 fourteen years later.
Virchows Arch

5
Methods: Previous recognitions of the body were performed in 1787, Salvatore Hospital L'Aquila, Italy, Division of Pathology, San
1904, and 1987, but no special procedure aimed at paleopathologic in- Salvatore Hospital, L'Aquila, Italy
vestigation at that time. The fourth Canonical Recognition of the Blessed
took place in February-march 2018. His mummy underwent external Background & Objectives: The Pathology Collection of Turin houses
examination and on-site digital radiography. around 300 wet specimens dating back to XIX-XX century. Most of them
Results: The extremely well-preserved, complete mummy belonged to an are in their original jars with labels describing year, necropsy number and
old male in good nutritional status. Marked dental wear and parodontal diagnosis. Four cases originally diagnosed as uterine myosarcoma, lung
disease, in the absence of caries, were identified, along with artificial remod- cancer and pleural sarcomas underwent modern diagnostic revision and
elling of face and feet. A huge swelling in the left groin, as well as parallel DNA evaluation by conservative sampling.
clean cuts of mummified skin were observed on shoulders and groins. No Methods: As the chemical composition of the storage fluids is unknown,
evidence of internal filling, sutures or fresh cuts was noted. Circular calcium pH value was measured in each specimen. Samples from the specimens
deposits in the left costophrenic angle were displayed by radiography. were submitted to routine histology, histochemistry and immunohisto-
Conclusion: The absence of evisceration signs rules out artificial chemistry. Additional tiny samples underwent DNA extraction and anal-
embalming, indicating a natural mummy. Clean cuts on shoulders and ysis by spectrophotometry and electrophoretic run in agarose gel. In order
groin may be related to limb mobilization tests performed in ancient to verify DNA integrity, short tandem repeat (STR) analysis employed for
times. Calcification might be referred to pleural infection/effusion or personal identification was performed.
splenic pathology. Results: The revised diagnoses were necrotic lung carcinoma, uterine
leiomyosarcoma, lung metastases from squamous carcinoma of unknown
primary and from uterine leiomyosarcoma. pH values were 2.56, 3.15,
OFP-09-004 4.45 and 4.65. The first two samples gave negative results on both spec-
Paleopathology of two mummified bodies from the Takarkori rock trophotometric and electrophoretic analysis. The other two showed low
shelter (SW Libya, 6100-5600 years BP) DNA quantities of moderate quality. STR analysis displayed DNA frag-
L. Ventura1, C. Mercurio1, G. Fornaciari2 mentation. The amplification of amelogenin STRs of chromosome X
1
Division of Pathology, San Salvatore Hospital, L'Aquila, Italy, allowed the precise identification in one case.
2
Division of Paleopathology, Department of Translational Research Conclusion: Pathology Collections harbour diseases that no longer exist
and New Technologies in Medicine and Surgery, University of Pisa, Italy or with natural course unmodified. They are an actual biological archive
and may represent a valid source for research on molecular features of
Background & Objectives: Two naturally mummified individuals from ancient diseases. Despite unreliable immunohistochemical results, mor-
the Takarkori rock shelter (Tadrart Acacus Mountains, central Sahara, SW phology and histochemistry addressed to final diagnosis. Although better
Libya), dating back to the Middle Pastoral period (ca. 6100-5000 years preserved in alkaline medium, acceptable quantity/quality DNA may be
BP), were unearthed together with the skeletal remains of thirteen further obtained also from specimens in moderately acid pH.
individuals. Takarkori is considered a key site to understand Holocene
human occupation in the central Sahara, giving insights on the funerary
practices of pastoral groups in the region. OFP-09-006
Methods: The partially mummified bodies of two females (TK-H1, TK- The historical roots of theranostic revealed by the genealogical and
H9), respectively dating back to 6090+60 and 5600+70 years BP, phylogenetic portrayal of tumours by pathologists
underwent radiologic, CT scanning, and macroscopic examination. C. Laboisse1
1
Selected samples of bones, tendons, intervertebral disks, skeletal muscles, Anatomie Pathologique Faculté de Médecine Université de Nantes,
vessels, skin and bowels were submitted to stereomicroscopy and histol- France
ogy examination.
Results: TK-H1 was a 30-35 years old woman, showing cranial vault Background & Objectives: The representation of tumours first based in
porotic hyperostosis, a repaired left ulnar fracture, a sclerotic lesion of the the 1800s on gross pathology and later on histopathology captures the
femur consistent with enostosis (bone island), and multiple Harris’ lines of ontological status (benign vs malignant) of tumours, considered for a long
proximal left tibia. TK-H9 was a skeletally mature individual, largely in- time as the sole contribution of pathology to therapy. In the1900s the
complete, without significant radiologic findings. Histology highlighted genealogical relation between normal and neoplastic tissues unveiled by
fibrous tissue with taphonomic changes, striated skeletal muscle, regular histopathology was used for therapeutic strategies.
compact and lamellar bone, and visceral walls with endoluminal vegetal Methods: The hormonal sensitivity of breast carcinomas was exploited
fibres and ectoparasites. Diffuse fungal colonization was also noted. by Beatson in 1896.The recapitulation by seminomas of the exquisite
Conclusion: Along with the exceptional findings at Uan Muhuggiag and sensitivity of normal gonadal cells to X rays was exploited by Béclère
Fozzigiaren, the Takarkori bodies represent extraordinary mummified who successfully proposed radiation therapy for this specific tumour type,
examples from that area. Although incomplete, they showed evidence thus creating the first theranostic in 1906. In 1943, the serendipitous
of trauma and carential alterations. These individuals represent the oldest observation of lymphopenias following exposure to nitrogen mustard
examples of mummies successfully submitted to histologic examination. led Goodman and Gilman to use this agent to treat lymphomas. In the
Fungal spores, not to be confused with erytrocytes, are a constant finding 1980s the CD20 targeting immunotherapty of B-cell lymphomas was an
in paleohistology, with no pathologic significance. extension of the genealogical imprint therapeutic strategy.
Results: During the 1980s advances in cancer genomics have
spurred pathologists to add a new dimension to the portrayal of
OFP-09-005 tumours by capturing their phylogeny i.e. the driver molecular
Histopathology and DNA evaluation of wet specimens from the events of neoplasia. Their work paved the way for the development
Pathology Collection of Turin of immunohistochemical and/or in situ hybridization companion
L. Ferrari1, J. Metovic2, D. Rullo3, D. Pulcinelli4, A. Lombardi4, F. tests intended as guides for adapting a drug to a specific patient.
Papola4, L. Ventura5 Interestingly the actionability of driver events was constrained by
1
Division of Pathology Cardinal Massaia Hospital Asti, Italy, the tissue genealogy of tumours.
2
Departments of Oncology Pathology Unit University of Turin Torino, Conclusion: Finally, the ontophylogenetical portray of tumours is now
Italy, 3 Division of Pathology San Salvatore Hospital L'Aquila, Italy, exploited to determine the eligibility of patients for immune checkpoint
4
Regional Centre of Immunohematology and Tissue typing San blockade therapy
 Virchows Arch

OFP-09-007 Conclusion: Digital pathology is appropriate for primary histopathology

Scorenado: a customisable, user-friendly and open-source visual as- diagnosis. Successful complete digitization relies on sample tracking and
sessment tool for histological slides integration of the information technology infrastructure. Rapid and reli-
M.D. Eichmann1, S. Reinhard1, I. Zlobec1 able scanning at 40x equivalent enabled the transition to a fully digital
1
University of Bern, Switzerland workflow. Digital pathology associated to efficiency gains in the pre- and
analytical phases, and creates the foundation for the adoption of compu-
Background & Objectives: Despite significant advances in the field of tational pathology.
digital image analysis, visual assessment of histological slides by human
experts is far from being rendered obsolete. This is due to the absence of
reliable, broadly available, and ready-to-use image analysis algorithms OFP-09-009
and the increasing demand of expert image annotations for the develop- Digital immunohistochemical evaluation of PDL1 in lung carcinomas
ment of state of the art image analysis algorithms. Here, we present highly correlates with manual method
Scorenado, a software solution for user-friendly visual assessment of B. Aszódi1, T. Micsik2
1
whole-tissue slide and tissue microarrays (TMA) images, including im- Semmelweis University, Budapest, Hungary, 2 1st Department of
age annotation quality evaluation. Pathology and Experimental Cancer Research, Semmelweis University,
Methods: For broad compatibility, Scorenado was developed as an open- Budapest, Hungary
source, cross-browser web tool in jQuery for individual users and groups
in close collaboration with pathologists. It has been extensively tested in Background & Objectives: PDL1- blockers are immune checkpoint
numerous histopathological research projects, generating a substantial inhibitors, which offer a successful way of treatment in various solid
amount of feedback on its usability and functionality, which has informed cancers. The initiation of the threapy requires the definition of PDL1
further development of the software. It runs on an Apache web server immunpositiviy by Tumour/Combined Positivity Score (T/CPS) with dif-
with PHP and on a Maria database. Additionally, Groovy scripts were ferent antibodies. It may sometimes be difficult. Our aim was to set up a
written for the open-source software QuPath to automate the creation of Digital Image Analysis (DIA) algorythm for PDL1 immunohistochemis-
TMA spot or tissue tile image collections for the use in Scorenado. try and compare its results to manual microscopic evaluation.
Results: Scorenado provides researchers with ready-to use annotation tem- Methods: 156 PDL1 (Dako 22C3 antibody) stained slides were scanned
plates but also permits to define custom parameters of interest. It automati- with Pannoramic Flash 250 Scanner (3DHistech, Hungary). DIA was trained
cally optimises its graphical user interface accordingly. In combination with on 50 randomly selected slides using 3DHistech’s softwares. Subsequently,
the randomisation of presented images, this facilitates visual assessment in a automatic whole slide image analysis was processed on 130 PDL1-slides.
blinded, and time-efficient manner. Additionally, Scorenado includes inter- Results: With various comparison of results, 0.75-0.89, strong correlation
and intra-rater reliability assessment features for recorded image annotations. was found between the digital and microscopic evaluation of PDL1-
So far, Scorenado has been successfully used for visual assessment of tumour slides. Clinical follow up is in progress to compare digital results with
buds, immune cells, protein expression, and colorectal polyp tissue classes, patients’ response.
totalling 97,332 TMA slide spots and 4,266 whole-tissue slide tiles. Conclusion: PDL1 immunohistochemical evaluation is usually required
Conclusion: Incorporating Scorenado into the research routine not only in order to begin immune checkpoint inhibitor therapy. There is inter - and
allows researchers to efficiently evaluate TMA and whole-tissue slides intarobserver variability in results which can influence patients’ therapy.
but also assists the evaluation of the quality of recorded image annota- Our Digital PDL1 Image Analysis algorythm successfully differentiated
tions. Finally, Scorenado greatly facilitates the creation of expert annotat- immune cells (lymhocytes and macrophages) from tumour cells and
ed datasets which may have the potential to significantly advance digital succeeded to define immunopositivity score in a standardised way - high-
clinical histopathology. ly correating with traditional methods. Theoretically the standardised dig-
ital PDL1 evaluation could reduce intra- and interobserver variability,
thus help better treatment targeting.
OFP-09-008
Complete digital pathology for routine histopathology diagnosis: 2
year's experience at Granada University Hospitals, Spain OFP-09-010
J.A. Retamero1, J. Aneiros1, R. G del Moral1 Convolutional neural networks can accurately distinguish histologic
1
Granada University Hospitals, Spain subtypes of pulmonary high-grade neuroendocrine tumours on dig-
ital whole-slide images
Background & Objectives: Complete digital pathology for routine histo- M. Ilie1, F. Henderson2, J. Benzaquen3, S. Heeke4, E. Long-Mira1, S.
pathology diagnosis has been implemented in few laboratories worldwide. Lassalle1, J. Fayada5, M. Hamila5, M. Poudenx3, C. Marquette3, V.
Granada University Hospitals (GUH) which comprises two teaching and two Hofman1,5, P. Hofman1,5
1
peripheral district general hospitals integrated in the Spanish National Health Universitè Côte d'Azur, CHU de Nice, University Hospital Federation
System, implemented digital pathology for primary diagnosis in 2016. We OncoAge, Laboratory of Clinical and Experimental Pathology, Nice,
describe the methodology adopted and resulting experience. France, 2 Indica Labs, Applications Department EMEA, London, United
Methods: All the glass slides generated for routine histopathology diagnosis Kingdom, 3 Universitè Côte d'Azur, CHU de Nice, University Hospital
were digitized at x40 using the Philips IntelliSite Pathology Solution, that Federation OncoAge, Department of Pulmonary Medicine and Oncology,
comprises an Ultra-Fast Scanner (UFS) and an Image Management System Nice, France, 4 Team 4 IRCAN, Inserm U1081/CNRS 7284, IRCAN,
(IMS). All hematoxylin and eosin (H&E) stained preparations, as well as Nice, France, 5 Universitè Côte d'Azur, CHU de Nice, University Hospital
immunohistochemistry (IHC) and histochemistry slides were scanned. The Federation OncoAge, Hospital-Integrated Biobank (BB-0033-00025), Nice,
existing sample tracking software and IMS were integrated to allow data France
interchange by means of Health Level 7 (HL7) protocol.
Results: More than 180,000 specimens have been reported using digital Background & Objectives: The histological distinction between small
pathology as primary means of diagnosis. This comprises circa one mil- cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma
lion digitized glass slides. The scanning error rate during the implemen- (LCNEC) can be challenging in some cases, while bearing prognostic
tation phase was below 1.5%, and subsequent slide production optimiza- and therapy significance. Moreover, there are borderline high-grade neu-
tion reduced this rate to 1 per 1000. Since implementation, GUH pathol- roendocrine carcinomas that morphologically fall between LCNEC and
ogists signed out 21% more cases per year on average. . SCLC. To assist pathologists with the differentiation of histologic
Virchows Arch

1
subtyping, we applied a deep learning classifier equipped with International Agency for Research on Cancer/WHO, France,
2
convolutional neural network (CNN; HALO-AI, Indica Labs, UK) to International Agency for Research on Cancer/WHO, Gambia, 3 GHIS
recognize pure and combined SCLC and LCNEC. Disease Control and Elimination, MRC Unit, Gambia, 4 Pathology
Methods: Slides of primary lung SCLC and LCNEC were obtained from Department, Edward Francis Small Teaching Hospital (EFSTH),
the Laboratory of Clinical and Experimental Pathology (University Banjul, Gambia
Hospital Nice, France). The HALO-AI module trained with 10,324 image
tiles extracted from 40 slides (SCLC and LCNEC) was evaluated on 20 Background & Objectives: Hepatocellular carcinoma (HCC) is the
slides (SCLC, LCNEC and combined SCLC and LCNEC) by F1-score and most common malignancy in The Gambia where the prevalence
accuracy using manual tumour annotations by three senior pathologists. of Hepatitis B virus is high. The International Agency for
Results: The tumour maps were false coloured and displayed side-by- Research on Cancer (IARC) initiated and follows the Gambia
side to original H&E slides with superimposed pathologist annotations. Hepatitis Intervention Study (GHIS) since 1986, as a randomized
Subsequently, confusion matrices representing the classification perfor- trial of infant Hepatitis B vaccination aiming to prevent HCC in
mance was calculated for each digital slide. The trained HALO-AI adult life. The cohort of over 120,000 children is now in early
yielded F1-scores of 0.86 (LCNEC), 0.83 (SCLC), and 0.81 (combined 30’s. Since 2015, liver biopsies taken from Gambian patients are
SCLC/LCNEC), respectively. The overall accuracy of distinguishing the evaluated at IARC. We report the morphological features of liver
two histotypes was 87%. disease based on the pathology platform developed under this
Conclusion: Our CNN model trained on a limited number of slides could collaboration.
work side-by-side with the pathologist to accurately differentiate between Methods: With the support from IARC and the local feasibilities, we set
SCLC and LCNEC in challenging cases. up the pathology workflow for liver biopsies. Biopsies from Gambian
patients who fulfil the eligibility criteria for liver biopsy are processed in
the local hospital (EFSTH) and the paraffin blocks are shipped to IARC
OFP-09-011 for microscopic evaluation. We use modified hepatitis activity index
Pathology teaching: the use of art and active methodologies (mHAI) and METAVIR to score the necroinflammatory activity (grade)
J. Melo1, V. Holanda Ferreira2, F. Klezevski Pimentel2, A. Santiago and the degree of fibrosis (stage) of liver parenchyma. Diagnosis of HCC
Nogueira2, P. Rocha Aguiar Neto2, L. Carvalho Figueira2, D. Nunes is confirmed by immunohistochemistry when any or both of HepPAr1
Oliveira1, M. Luiz Balancin3, S.A. de Souza Júnior2 and Arginase 1 are positive. We grade the differentiation by applying two
1
Department of Pathology, Postgraduate Program in Public Health, methods: four-tired Edmondson-Steiner as well as three-tired score of
Faculty of Medicine, University of Fortaleza, Brazil, 2 Faculty of well, moderately, and poorly differentiated.
Medicine, University of Fortaleza, Brazil, 3 Pathology Division, Clinics Results: From May 2015 to December 2018, we received 334 biopsies
Hospital, Faculty of Medicine, University of São Paulo, Brazil among them 211 were qualified as “satisfactory for evaluation”.
Insufficient tissue and/or low quality of tissue processing led to labelling
Background & Objectives: Undergraduate pathology teaching is a life- them as “insufficient for diagnosis”. 29 showed no significant patholog-
long challenge to medical educators and pathologists alike. In the context ical changes and 21 were diagnosed as “secondary” liver masses.
of a Problem Based Learning (PBL) curriculum, we have employed ar- Table below summarizes the morphological findings of 161 patients.
tistic and creativity tools to enhance pathology learning and compliance
in the undergraduate medical curriculum.
Methods: Discuss about pathology teaching.
Results: In the General Pathology module of the second year (MS2) Chronic hepatitis HCC
healing and repair are studied and a painting workshop is held, in which
sketches are made from the direct microscopic visualization of slides by the Number* 84 77
students, while discussing the phases and biological properties of the pro- Mean age (SD) 41.0 (14.0) 47.0 (15.0)
cess. During second and third years, reporting and requesting a report is Male (%) 86% 85%
practiced to understand the clinical concepts of pathology practice. Theatre HBs-Ag positive 80% 48%
practice is employed to discuss pathogenesis between small student groups.
Grade by ISHAK; Mean (SD) 9.0 (4.0)
Autopsy practices in a local coroner division is held during third year. In
these practices, students perform an autopsy exam while supervised by Stage by ISHAK; Mean (SD) 4.0 (2.0)
instructors, generating awareness of the technical and ethical backgrounds Activity by METAVIR; Mean (SD) 2.0 (1.0)
of Medical practice. Digital resources are also employed, as a website to Stage by METAVIRM; Mean (SD) 3.0 (1.0)
teach autopsy practice, digital flash cards and online tools as Socrative and
Kahoot. In these applications, teachers or monitors can create virtual class- Grade of HCC (Edmondson-Steiner)
rooms for interactive and simultaneous access of participants, allowing the Well differentiated (I, II) 15%
monitoring of the pace of learning of students through a control panel that Moderately differentiated (III) 69%
represents, immediately, the performance of students in real time. Poorly differentiated (IV) 16%
Conclusion: The so-called active methodologies are being used,
Elastography (MSTIF); Mean (SD) 22.7 (21.0) 62.0 (42.0)
questioning and motivating students and teachers alike, engaging and
enhancing the general perception and awareness of pathology as a clinical *There are missing data for all estimates up to 29% of data.
medical specialty.

Conclusion: Set up of efficient clinical and diagnostic approaches in a

OFP-09-012 low-income country is challenging but possible. The supportive role of
Morphological features of liver biopsies from The Gambia, West organisations such as IARC to provide necessary infrastructure and facil-
Africa: first pathology report from the "Gambia Hepatitis itate training programs is not negligible for this performance. In this
Intervention Study" by the International Agency for Research on context, we succeed to set up an adapted pathology workflow that en-
Cancer abled us to create and describe here the first documented pathology data
B. Abedi-Ardekani1, D. Nasrollahzadeh1, R. Njie2,3, S.O. Bittaye3, C. on liver diseases, the most important public health problem, in The
Carreira1, M. Salieu Jallow4, M. Almonte1, C.P. Wild1 Gambia.
 Virchows Arch

OFP-09-013 coupled with patients’ clinical data from the patient registries as well as
Sectioning-free virtual H&E imaging of tissue samples with two- with the data retrieved from the national health registries. As pulmonary
photon microscopy carcinoid (PC) tumours are rare tumours, we decided to utilize biobanks
J.P. Kolb1, M. Strauch1, D. Weng1, M. Wacker1, W. Draxinger1, S. to collect a nationwide PC tumour cohort.
Karpf1, R. Huber1 Methods: We applied for clinical data and tissue material from primary
1
University of Lübeck, Germany PC tumour patients operated on between 2002 and 2011 from all appro-
priate Finnish biobanks (n=6). Data on PC incidence was retrieved from
Background & Objectives: Paraffin sectioning is a time- and labor- the Finnish Cancer Registry.
intensive step in the routine pathology workflow. Frozen sectioning is much Results: According to the Finnish Cancer Registry, 227 PCs (216 typical
faster but results in a lower quality of the sections. We use two-photon carcinoid (TC) and 9 atypical carcinoid (AC) tumours) were diagnosed
microscopy (TPM) of bulk tissue samples to create images resembling stan- nationally from the primary tumour tissue sample (biopsy or resection)
dard H&E-stained slides without any sectioning. In addition to simplifying between 2002 and 2011. Processing time in the biobanks from application
the pathology workflow, this rapid technology can provide 3-dimensional to material delivery varied between 6 and 24 months. Altogether, we
histological images that could lead to higher diagnostic value of the data. received 125 resected PC tumours coupled with clinical data. After re-
Methods: In order to achieve an H&E compatible staining, bulk tissue evaluation, 98 (78%) were classified as TC and 27 (22%) as AC. Here we
samples are quick-stained (2-10 min) with acridine orange (nuclei stain) describe the major reasons for relatively low number of tumours found in
and sulforhodamine 101 (counterstain) without any sectioning. The tissue the biobanks as well as discuss the annotation bias observed in the pri-
samples are imaged using our home-built two-photon microscope achiev- mary diagnostic database. In addition, the bottlenecks and advantages of
ing high three-dimensional resolution volumetric data records. This is pathology integrated biobanking are discussed.
achieved through the inherent confocality of the nonlinear TPM process. Conclusion: Finnish biobanks are a valuable resource for studying rare
Two separate spectral channels (nuclei- and counterstain) are recorded tumours. However, expert pathologists are needed to find the suitable
and merged to create an H&E-equivalent image ready for histological samples. Moreover, re-classification of the samples collected during de-
assessment and post-process digital sectioning. cades is a necessity.
Results: We successfully recorded sectioning-free H&E-like images with our
two-photon microscope with considerably less work compared to conven-
Tuesday, 10 September 2019, 08:30 - 12:00, Galliéni 5
tional paraffin-sectioning. Comparison of TPM and conventional H&E sec-
OFP-10 | Joint Session: Pulmonary Pathology / Thymic
tioning by other groups has shown similar image quality, but the equivalence
still needs to be proven conclusively. Further, additional speed improvements and Mediastinal Pathology
are required. This will be feasible using improved system hardware and also
implementing parallel processing of the volumetric dataset.
Conclusion: Virtual H&E imaging with TPM will simplify the pathology OFP-10-001
workflow in the future if the challenges of higher imaging speed and data Vascular endothelial growth factor (VEGF) and its receptors expres-
processing are met. The simple creation of 3D images and the potential sion in lung carcinoids: clinicopathological correlation
combination with other imaging modalities (e.g. TPM fluorescence-life- F. Fortarezza1, F. Pezzuto1, F. Lunardi1, G. Comacchio1, F. Rea1, F.
time-imaging), might increase the diagnostic accuracy. Future research Calabrese1
1
will investigate the comparability to standard H&E staining and fluores- University of Padua, Italy
cent immunostains.
Background & Objectives: Lung carcinoids are neuroendocrine tu-
Hillenkamp Fellowship by SPIE, European Union (ERC-CoG no. mours classified in two histological subtypes, typical and atypical,
646669, Interreg CELLTOM), German Research Foundation (HU1006/ based on the mitotic index and the presence of necrosis. They are
6,EXC 306/2), German Federal Ministry of Education and Research considered low-grade tumours, although metastases, recurrences may
(BMBF no.13GW0227B: “Neuro-OCT”) occur, particularly in atypical forms. Several morphological features
(proliferative index, tumour size and vascular invasion) have been
studied for a better prognostic stratification, but the results are incon-
OFP-09-014 clusive. These tumours are usually highly vascularized thus the eval-
A nationwide pulmonary carcinoid tumour cohort collected from the uation of angiogenetic factors has emerged as a diagnostic and ther-
Finnish clinical pathology integrated biobanks apeutic tool.
T. Vesterinen1, K. Salmenkivi1, H. Mustonen2, T. Kuopio3, E. Lappi- Methods: The aim of the study was the evaluation of the VEGF pathway,
Blanco4, T. Paavonen5, P. Vainio6, A. Knuuttila7, C. Haglund2, J. Arola1 mainly involved in angiogenetic mechanisms. A retrospective and observa-
1 tional study was carried out on 79 lung carcinoids (62 typical, 17 atypical),
HUSLAB, Department of Pathology, University of Helsinki and
Helsinki University Hospital, Finland, 2 Department of Surgery, consecutively resected from 2005 to 2011 at the Thoracic Surgery Division
University of Helsinki and Helsinki University Hospital, Finland, of Padua University. The expressions of VEGF and VEGFR1, VEGFR2,
3 and VEGFR3 receptors were evaluated by immunohistochemical assay and
Department of Biological and Environmental Science, University of
Jyväskylä and Department of Pathology, Central Finland Health Care then correlated with morphological (histotype, staging, proliferative index)
District, Finland, 4 Department of Pathology, Center for Cancer and clinical (age, sex, tabagism, follow-up) features.
Research and Translational Medicine, Oulu University Hospital and Results: Atypical carcinoids showed bigger tumour size (p = 0.03), higher
University of Oulu, Finland, 5 Department of Pathology, Fimlab proliferative index (p < 0.0001) and higher expression of VEGF (p = 0.02),
Laboratories and Department of Medicine and Life Sciences, University VEGFR1 (p = 0.01), VEGFR2 (p < 0.001) and VEGFR3 (p < 0.001) than
of Tampere, Finland, 6 Department of Pathology, University of Turku and typical ones. Interestingly, VEGFR3 expression directly correlated with pro-
Turku University Hospital, Finland, 7 Department of Pulmonary liferative index (p = 0.05). VEGFR3 expressions were related to the presence
Medicine, Heart and Lung Center, and Cancer Center, University of of lymphnode metastatization independently from histotype (p < 0.005).
Helsinki and Helsinki University Hospital, Finland Age, sex and tabagism did not influence tissue expression of any receptor.
Conclusion: High expression of the VEGF pathway, particularly
Background & Objectives: Finnish biobanks administer millions of VEGFR3, in atypical and typical metastatic carcinoids could be a sub-
tissue samples collected within the clinical diagnostics between 1990 strate for mechanistic studies to validate its prognostic and predictive
and 2013. According to the Finnish Biobank Act, these samples can be value.
Virchows Arch

OFP-10-002 University Medical Centre Utrecht, The Netherlands, 4 Netherlands

Biomarkers in lung cancer: descriptive analysis of a centralised plat- Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands
form in Spain (Lungpath)
J. Martin Lopez1, A. Brito Garcia2, E. Gallego Dominguez3, J. Bautista Background & Objectives: Adequate and timely testing for genetic
Laforga4, J.L. Lopez Hidalgo5, M.I. Esteban Rodriguez6, M.d.C. Saez alterations in non-small cell lung cancer (NSCLC) is necessary to
Rodriguez 7 , I. Sansano Valero 8 , M. Medina Perez 9 , A. Benito consider targeted therapy when a certain genetic alteration is present.
Berlinches 10 , F. Perez Ochoa 11 , F. Dominguez 12 , A. Sanchez Previously, we demonstrated that in the Netherlands molecular test-
Espinosa13, H.H. Torres Rivas14, N. Mancheño Franch15, P. Machin ing was suboptimal in 2015, as 25% (EGFR/KRAS and ALK) to 50%
Andreu16, A. Lerin Martos17, T. Hernandez Iglesias18, A. Martinez (ROS1) of patients were not tested according to guidelines, and no-
Pozo18, C. Salas Anton1 table laboratory variation was present. Currently, by analyzing a co-
1
Department of Pathology. Hospital Universitario Puerta de Hierro, hort of metastatic NSCLC from 2017 we aim to assess whether the
Spain, 2 Hospital Universitario de Canarias. Santa Cruz de Tenerife, performance of molecular testing improved.
Spain, 3 Hospital Universitario Virgen de la Victoria. Malaga, Spain, Methods: All fully registered stage IV non-squamous NSCLC with in-
4
Hospital Universitario Doctor Peset. Valencia, Spain, 5 Hospital cidence year 2017 from the Netherlands Cancer Registry were matched to
Universitario Campus de la Salud. Granada, Spain, 6 Hospital the Dutch pathology registry (PALGA). Using information extracted
Universitario La Paz. Madrid, Spain, 7 Hospital Universitario Clinico from pathology excerpts, proportions of tumours tested for
San Carlos. Madrid, Spain, 8 Hospital Universitario Vall d´Hebron. EGFR/KRAS, BRAF, and HER2 mutation, ALK, ROS1, and RET rear-
Barcelona, Spain, 9 Hospital Universitario Reina Sofia. Cordoba, Spain, rangement <3 months after diagnosis were determined.
10
Hospital Universitario Ramón y Cajal. Madrid, Spain, 11 Hospital Results: Of 2596 identified patients, we have currently analysed
Universitario Mutua de Terrassa. Barcelona, Spain, 12 Hospital de 511 (20%). Twenty-three patients were non-eligible after matching,
Cabueñes. Gijon, Spain, 13 Hospital Universitario de Cartagena, Spain, leaving 488 patients. EGFR/KRAS testing was performed in 412
14
Hospital Universitario Central de Asturias. Oviedo, Spain, 15 Hospital patients (84.4%). Of the EGFR/KRAS wildtype tumours (n=184),
Universitario y Politècnico La Fè. Valencia, Saint Vincent and the 167 (90.8%) were tested for BRAF, 158 (85.9%) for HER2, 157
Grenadines, 16 Consorci Sanitari Integral. Barcelona, Spain, 17 Hospital (85.3%) for ALK, 110 (59.8%) for ROS1, and 73 (39.7%) for
Sant Pau i Santa Tecla. Tarragona, Spain, 18 SEAP, Spain RET. Insufficient tumour tissue and inappropriate specimen were
the most stated reasons for not testing.
Background & Objectives: Biomarker testing on pathology specimens Conclusion: These preliminary data show significantly higher
is an essential requirement to properly treat lung cancer (LC) patients. Is EGFR/KRAS and ALK testing proportions compared to 2015. Further
undeniable the increasing number of LC predictive biomarkers, as the improvement remains possible to identify candidates for targeted therapy.
increasing development of targeted therapies. LungPath is an on-line tool At the ECP meeting, we expect to present the variation between labora-
developed by the Spanish Society of Pathology (SEAP) with free and tories for the entire cohort.
voluntary participation of differents Departments of Pathology to registry,
monitor and trace biomarker results in clinical practice. After initial data This work was funded by Roche, Pfizer, AstraZeneca.
reclutation step, first objective is to realize a descriptive analysis of
LungPath.
Methods: Descriptive analysis of Lungpath. Biomarkers determina- OFP-10-004
tions of LC patients were collected from March 2018 to January Interlaboratory variation in PD-L1 positivity in non-small cell lung
2019, from 38 Spanish Departments of Pathology. cancer patients: a comparison between histological and cytological
Results: Based on this real clinical practice database, 19.332 biomarkers material
were tested over a total of 4.773 samples from LC patients. Small lung B. Koomen1, R. Voorham2, C. Kuijpers1, I. Deckers2, S. Willems1
1
biopsies (60%), surgical resection specimen (16,3%) and cell block cy- Department of Pathology, University Medical Centre Utrecht,
tology (10,7%), fine needle aspiration cytology (5,1%), blood (2,5%) and The Netherlands, 2 PALGA Foundation (the nationwide network and
other non lung biopsies (5,4%). registry of histo- and cytopathology in The Netherlands), Houten,
The subtypes were adenocarcinoma (66%), squamous cell carcinoma The Netherlands
(SCC) (19%), large cell neuroendocrine carcinoma (3,7%), large cell
carcinoma (0,3%) and non-small cell lung cancer (NOS) (6,1%). The Background & Objectives: Immunohistochemical expression of pro-
most frequently biomarker tested was EGFR mutation (91,4%) followed grammed death ligand 1 (PD-L1) is used to select patients with non-
by ALK traslocation (80,1%), PD-L1 expression (58,1%) and ROS1 small cell lung cancer (NSCLC) for immunotherapy. PD-L1 immunohis-
traslocation (56,2%) in non-squamous histology and PD-L1 expression tochemistry (IHC) has been validated in histological material but is often
(73,6%) in SCC. Plus forward information obtained. performed on cytological material. This study aims to determine if
Conclusion: No similar data regarding LC predictive biomarker has been interlaboratory variation in PD-L1 positivity differs between histological
published before in Spain. and cytological material.
Lungpath provide an opportunity to registry clinical practice data and in Methods: Using the Dutch Pathology Registry (PALGA), pathology re-
the future could be an useful tool to monitor, correlate results between ports of NSCLC patients between 01-07-2017 and 30-06-2018 from all
different centers and improve the available knowledge regarding bio- Dutch pathology laboratories were identified. For each laboratory, the
markers in LC. proportion of reported PD-L1 positive cases was determined for histolog-
ical and cytological material separately, using two cutoffs (1% and 50%).
Proportions were compared between laboratories by creating funnel plots
OFP-10-003 with 95%-confidence intervals (CI). For analysis of histological material,
Evaluation of molecular testing in a Dutch cohort of metastatic non- 4005 patients from 27 laboratories were included. For analysis of cyto-
small cell lung cancer patients from 2017 logical material, 1098 patients from 21 laboratories were included.
C. Kuijpers1, M. van den Heuvel2, A. van Lindert3, R. Damhuis4, S. Results: Analyzing histological material, 55.7% of cases were PD-L1
Willems1 positive using the 1%-cutoff. Eight (29.6%) laboratories fell outside the
1
Department of Pathology, University Medical Centre Utrecht, Utrecht, 95%-CI, differing significantly from the mean. Using the 50%-cutoff,
The Netherlands, 2 Department of Lung Disease, Radboudumc, 30.5% of cases were PD-L1 positive. Three (11.1%) laboratories differed
Nijmegen, The Netherlands, 3 Department of Respiratory Medicine, significantly from this average. Analyzing cytological material, 51.1% of
 Virchows Arch

cases were PD-L1 positive using the 1%-cutoff. Eight (38.1%) laborato- in a retrospective small series of translocated lung adenocarcinomas of
ries differed significantly from the mean. Using the 50%-cutoff, 28.5% of known status that LD-RTPCR assay could efficiently identify ALK,
cases were PD-L1 positive. Four (19.0%) laboratories differed signifi- ROS and RET rearrangements with a sensitivity of 64% and with per-
cantly from the mean. fect specificity. Here, we report an upgraded version of this assay used
Conclusion: Interlaboratory variation in PD-L1 positivity was greater for in a rou tin e prospective coho rt o f newly diagno sed lung
IHC performed on cytological material than for IHC performed on histo- adenocarcinomas.
logical material. Furthermore, variation was greater for the 1%-cutoff Methods: Prospective cases of newly diagnosed lung carcinomas
than for the 50%-cutoff in both material types. referred to the molecular platform of Rouen University Hospital
between 2018 and 2019 for ALK and ROS IHC, high throughput
This research was funded by AstraZeneca, Roche Diagnostics and MSD. molecular testing and sometimes FISH were tested in parallel with
the LD-RTPCR assay. This technique was designed to detect at
one go ALK, ROS and RET translocations (with identification of
OFP-10-005 the partner gene) and MET exon 14 skipping at minimal cost (less
Reduced isolated red signal pattern of ALK FISH in lung cancer than 5 euros) and with results in two days.
patients Results: 328 lung carcinomas were included in our study. The LD-
I. Kocsmar1, G. Smuk2, G. Pajor2, î Kocsmár1, K. Szuhai3, T. Tornóczky2 RTPCR assay detected 9 of the 10 ALK and 3 of the 3 ROS
, G. Lotz1 translocated tumours positive for IHC and FISH, but also 5 of the
1
2nd Department of Pathology, Faculty of Medicine, Semmelweis 5 MET exon 14 skipping mutations observed by high throughput
University, Hungary, 2 Department of Pathology, Medical School, sequencing. In addition, it retrieved 5 molecular alterations that
University of Pècs, Hungary, 3 Department of Molecular Cell Biology, had been missed by the classical process: 3 MET exon 14 skipping
Leiden University Medical Center, The Netherlands mutations and 2 RET translocated tumours, then confirmed by other
means.
Background & Objectives: Autoimmune encephalitis can be triggered Conclusion: We successfully implemented LD-RTPCR for gene trans-
by infections, paraneoplastic disorders or it may be idiopathic, and pres- location and MET exon 14 skipping detection in routine analysis. This
ent by variety of clinical manifestations, which can be acute or subacute. technique is cheap, very fast, sensitive and specific, and easily upgrad-
We report the case of a 53-year-old patient, with no history of epilepsy or able (e.g. NTRK translocations). Owing to the overwhelming advan-
other neurological disorder, presenting with acute onset aphasia and dis- tages of this assay, we recommend considering it as the new reference
orientation that rapidly evolved to altered mental status, generalized for systematic testing of lung adenocarcinoma in parallel with IHC and
tonic-clonic seizures, respiratory difficulty and evolving to refractory sta- genotyping.
tus epilepticus, prompting admission to the intensive care unit. Normandie Valorisation, Rouen University Hospital, Boehringer
Methods: The patient had a personal history of essential
thrombocythemia and insulin-treated diabetes mellitus. Following exten-
sive investigation, vascular, paraneoplastic, infectious and metabolic ae- OFP-10-007
tiologies were excluded. Cerebral CT and MRI, and cerebrospinal fluid Birt-Hogg-Dubé (BHD) syndrome-associated lung cysts: histopatho-
analysis were normal. Serum and CSF evaluation of neuronal cell-surface logical analysis and differential diagnosis from miscellaneous cystic
antibodies (NMDA, AMPA, GABA, VGKC) was negative. lung diseases
Thyroglobulin antibodies and thyroid peroxidase antibodies were elevat- M. Furuya1, Y. Nakatani2
1
ed in serum and negative in the cerebrospinal fluid. Yokohama City University, Japan, 2 Yokosuka Kyosai Hospital, Japan
Results: Despite aggressive immunomodulatory treatment there was no
clinical improvement and after 46 days the patient died of a medical Background & Objectives: Birt-Hogg-Dubé (BHD) Syndrome is a rare
condition (septic shock). The main findings of the post-mortem neuro- hereditary disorder caused by FLCN germline mutation. Almost all indi-
pathologic examination were inflammatory lesions, namely microglial viduals with BHD syndrome have multiple lung cysts; however, the lung
nodules, distributed in the limbic region (hippocampus, entorhinal cortex specimens are often misdiagnosed as blebs/bullae or emphysema. The
and periamygdaloid cortex) and brainstem, particularly in the pons. No aim of the study is to clarify histopathological clues to differentiate
inclusions suggestive of viral infection were identified. BHD syndrome-associated cysts from miscellaneous cystic lung diseases.
Conclusion: Although the patient had high serum thyroid autoantibodies, Methods: We investigated FLCN mutations and clinicopathological find-
the lack of response to high-dose corticosteroid therapy along with the ings of 520 symptomatic individuals from 200 Japanese families with
neuropathological examination favour the diagnosis of seronegative lim- BHD syndrome. Lung specimens from 120 patients who underwent
bic and brainstem encephalitis and do not support the hypothesis of video-assisted thoracoscopic surgery (VATS) and an autopsied BHD
Hashimoto’s encephalopathy. We highlight the importance of neuropath- syndrome-associated lung were reviewed.
ological examination in refractory status epilepticus and further CSF Results: The cysts were preferentially distributed in the mediastinal and
studies are still being performed. lower regions. A number of cysts in the pulmonary central/hilar regions
abutted large bronchi and vessels. Microscopic analysis of specimens
showed that a typical parenchymal cyst localized astride interlobular sep-
OFP-10-006 ta, with a lining of benign-looking alveolar epithelium on the inner sur-
The new gold standard for detection of theranostic gene rearrange- face, and that most cysts had rugby oval rather than round shapes as they
ments in thoracic oncology is born: one-year prospective routine LD- intruded into and grew along the interstitial tissue surrounding bronchial
RTPCR in 328 newly-diagnosed lung adenocarcinomas trees and blood vessels.
N. Piton1, P. Ruminy2, M. Lanic2, A. Lamy1, F. Marguet1, F. Guisier1, M. Conclusion: Fibrous thickening and inflammation are frequently ob-
Salaün1, L. Thiberville1, F. Jardin2, J. Sabourin1 served in the vicinity of subpleural cysts; however, near complete epithe-
1
Rouen University Hospital, France, 2 Centre Henri Becquerel, France lial lining is demonstrated in most of BHD syndrome-associated cysts.
Other cystic lung diseases that must be distinguished include
Background & Objectives: ALK, ROS, RET translocations and MET lymphangioleiomyomatosis and cystic lesions of autoimmune diseases
exon 14 skipping may be difficult to detect by routine techniques, such as Sjögren's syndrome. Recognition of the aforementioned patho-
especially when specimens are exiguous. We recently demonstrated logical features allow pathologists to reach the correct diagnosis.
Virchows Arch

OFP-10-008 Using 22C3-LDT, 24% of cases were discordant. Again, most of these
Combined assessment of tumour mutational load, CD8+ T cell infil- (90%) showed lower TPS in fixcyt-fixed material compared to formalin.
tration, and expression of PD-L1 and HLA class I in small biopsy Concordance levels were equal for both cutoffs (kappa 0.72).
specimens to predict immunotherapy response in non-small cell lung Conclusion: Cytological specimens pre-fixed in an ethanol based fixative
cancer showed decreased PD-L1 immunostaining with both SP263 and 22C3-
D. Hurkmans1, M. Kuipers2, J. Smit2, R. Mathijssen1, P. Postmus2, P. LDT. Although concordance levels were still within the moderate or
Hiemstra2, J. Aerts3, R. van Marion4, S. van der Burg2, J. von der Thüsen3 substantial range, pre-fixation in ethanol based fixatives may increase
1
Erasmus MC Cancer Institute, Rotterdam, The Netherlands, 2 Leiden the risk of assigning patients to a lower PD-L1 TPS category.
University Medical Center, The Netherlands, 3 Erasmus Medical Center,
Rotterdam, The Netherlands, 4 Erasmus University Rotterdam,
The Netherlands OFP-10-010
Interstitial lung disease in systemic sclerosis is associated with auto-
Background & Objectives: A combination of biomarkers is likely to pro- immunity to α1(V) chain of type V collagen
vide more accurate prediction for response to immunotherapy in non-small A.P. Pereira Velosa1, L. Brito2,3, Z.A. Queiroz2, S. Carrasco2,3, J. Tomaz
cell lung cancer (NSCLC) patients than PD-L1 expression alone. In routine de Miranda2,3, C. Goldenstain-Schainberg2,3, E. Roger Parra2,4, V.L.
practice these need to be determined in small biopsy specimens, limiting the Capelozzi2,5, W. Rosolia Teodoro2,3
1
amount of material available for testing. The feasibility of assessment in Hospital das Clinicas HCFMUSP, Faculdade de Medicina,
small biopsy specimens of a series of mechanism-of-action based parameters Universidade de Sao Paulo, Brazil, 2 Faculdade de Medicina,
was studied for response prediction of immunotherapy. Universidade de Sao Paulo, Brazil, 3 Rheumatology Division, Brazil,
4
Methods: Retrospective cases of metastatic NSCLC patients (n=30) with Department of Pathology, Brazil, 5 Department of Rheumatology, Brazil
sufficient remaining archival tissue, obtained prior to the first nivolumab
administration, were selected. Tumour mutational load (TML) was deter- Background & Objectives: Interstitial lung diseases (ILD) are among
mined using a next-genome sequencing panel (409 cancer-related genes). the most serious complications associated with systemic sclerosis (SSc).
Immunohistochemistry was performed to score PD-L1, total CD8+ T cell Recently, type V collagen (ColV) has been associated to autoimmunity in
infiltration and HLA class I. pulmonary fibrosis. Our group have shown the pathogenic role of ColV in
Results: In all 30 patients with adenocarcinoma (67%) or squamous cell clinical and pre-clinical models of SSc. In this study, we evaluated the
carcinoma (33%) complete assessment of biomarkers was achieved, despite autoimmunity to α1(V) and α2(V) chains of the Col V in SSc-ILD.
the availability of limited amounts of tissue. TML alone as well as combina- Methods: Sera from 19 patients with SSc were tested for anticollagen V
tions of high TML, PD-L1 expression, high CD8+ T cell infiltrate, or no loss antibodies presence by flow cytometry. IgG fraction of the resulting pool
of HLA class I were significantly associated with better survival. of positive samples was isolated by affinity chromatography to further
Conclusion: This study underscores the feasibility of multimodality, biotinylation (ColV-IgG+). Adsorption of the biotinylated IgG with
combinatorial determination of PD-L1 expression, TML, CD8+ T cell α1(V) [ColV-IgG+/ads-α1(V)] and α2(V) [ColV-IgG+/ads-α2(V)]
infiltration and HLA class I expression as predictive biomarkers for the chains was employed to evaluate the spectrum of reactivity in lung biop-
response to anti-PD-1 immunotherapy in a real-life setting in NSCLC. sies obtained from SSc-ILD patients (n=4) by immunofluorescence. Eight
ColV-immunogenic peptides were tested to evaluate the reactivity in
ColV-positive sera samples of SSc patients.
OFP-10-009 Results: We found that 7 (36,84%) sera samples were reactive to ColV.
Decreased PD-L1 immunostaining in cytological specimens after fix- The SSc-ILD lung tissue immunostained with ColV-IgG+ showed in-
ation in an ethanol based fixative tense green fluorescence along of vascular basement membrane, bronchi-
B. Koomen1, W. Vreuls2, M. de Boer1, J. Hölters3, A. Vink1, S. Willems1 olar smooth muscle and adventitial layer, contrasting with the tenue ColV
1
Department of Pathology, University Medical Centre Utrecht, expression in control lung (32,86±8,018 vs. 0,4688±0,4688, p<0.05).
The Netherlands, 2 Department of Pathology, Canisius-Wilhelmina ColV-IgG+/ads-α1(V) showed decreased birefringence in SSc-ILD lung
Hospital, Nijmegen, The Netherlands, 3 Department of Pulmonology, tissue compared to ColV-IgG+ (10,05±4,585 vs. 32,86±8,018, p<0.05)
Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands and ColV-IgG+/ads-α2(V) (10,05±4,585 vs. 30,21±4,286, p<0.05).
ColV-positive sera samples of SSc patients presented immunoreactivity
Background & Objectives: Expression of programmed death-ligand 1 for Col5A1(599) and Col5A1(1.049) peptides.
(PD-L1) protein is used to select patients with non-small cell lung cancer Conclusion: We found that the autoimmunity to Col V is directed to
(NSCLC) for immunotherapy. PD-L1 immunostaining is often performed α1(V) chain, emerging as promisor biomarker of prognosis and target
on cytological material, but pre-analytical variables may affect PD-L1 therapy in SSc-ILD patients.
expression. We studied if pre-fixation in an ethanol based fixative leads
to a decrease in PD-L1 immunostaining, using a standardised assay FAPESP (2016/05617-4; 2017/11865-3), LIM
(SP263) and a laboratory-developed test (LDT) (22C3).
Methods: Transbronchial needle aspirates from 42 NSCLC patients were
fixed in both formalin and fixcyt (50% ethanol). Next, clots from both OFP-10-011
fixatives were processed into formalin-fixed paraffin-embedded blocks. Multivariate survival analysis reveals RAD51 protein as a superior
From each block, serial sections were stained for PD-L1 with SP263 prognostic factor compared to tumour infiltrating lymphocytes and
(Ventana Benchmark Ultra platform) and 22C3-LDT (Dako Omnis plat- PD-L1 expression in patients with resected non-small-cell lung
form). Tumour proportion scores (TPS) were determined, using three carcinoma
categories (<1%, 1-49%, ≥50%). TPS was compared between paired M. Gachechiladze1, J. Skarda2, V. Kolek3, P. Smickova3, Z. Kolar2, R.
samples from each patient. Stahel4, W. Weder5, U. Rulle6, A. Soltermann7, M. Joerger8
1
Results: Using SP263, 19% of cases showed discordant results between Department of Clinical and Molecular Pathology, Palacky University
formalin-fixed and fixcyt-fixed material, with 75% of discordant cases Olomouc, Czech Republic, 2 Department of Clinical and Molecular
showing lower TPS in fixcyt-fixed material. Dichotomizing data using Pathology, Palacky University and University Hospital Olomouc,
the 1%-cutoff showed a lower concordance level (kappa 0.71) than when Czech Republic, 3 Department of Tuberculosis and Respiratory Diseases,
the 50%-cutoff was used (kappa 0.88). Palacky University and University Hospital Olomouc, Czech Republic,
 Virchows Arch

4
Oncology Clinic, University Hospital Zurich, Switzerland, 5 Clinic of p.S310F), focal membranous and diffuse cytoplasmic/nuclear positivity
Thoracic Surgery, University Hospital Zurich, Switzerland, 6 Institute of was detected by IHC.
Pathology and Molecular Pathology, University Hospital Zurich, Conclusion: HER2 CNV is not a rare event in NSCLC, and it shows a
Switzerland, 7 Institute of Pathology and Molecular Pathology, University correlation with amplification, as determined with ISH. HER2 CNV/
Hospital Zurich, Switzerland, 8 Department of Oncology and Haematology, amplification is not a mutually exclusive driver event in lung carcinogen-
Cantonal Hospital St.Gallen, Switzerland esis, as it is observed in cases with other driver mutations.

Background & Objectives: DNA repair proteins have emerged as po-

tential predictors for immunotherapy response alongside PD-L1 expres- OFP-10-013
sion, tumour-infiltrating lymphocytes (TILs) and tumour mutational bur- Isolation and next-generation sequencing of RNA from microdissect-
den. The aim of the study was to analyse immunotherapy relevant alter- ed fibroblastic foci areas of patients with idiopathic pulmonary
ations in PD-L1 expression in tumour cells and in TILs; TIL count; fibrosis
expression of the major homologous recombination (HR) protein S.E. Vuljan1, F. Lunardi1, G. Esposito2, F. Pezzuto1, F. Fortarezza1, M.
RAD51; and their potential prognostic value in patients with resected Schiavon1, F. Rea1, F. Calabrese1
1
non-small-cell lung carcinoma (NSCLC). University of Padua, Italy, 2 Veneto Institute of Oncology, Italy
Methods: Tissue microarrays from 96 NSCLC patients from the
University Hospital Olomouc, Czech Republic (training set) and from Background & Objectives: Formalin-fixed paraffin embedded (FFPE)
1109 NSCLC patients from University Hospital Zurich, Switzerland (val- tissue is the most commonly used method to preserve and store tissue.
idation set), were stained by standard immunohistochemistry, using anti- However, its use is limited to molecular analysis due to RNA degradation
bodies against: RAD51; T cell markers - CD3 and CD8; macrophage and RNA-protein crosslinking during fixation which impacts on RNA
marker - CD68; and PD-L1. H-score for nuclear RAD51 and quantitative quality. Laser capture microdissection (LCM) is a powerful method to
scores for total (tumour + stromal) CD3, CD8 and CD68 were calculated. isolate specific populations of cells from heterogeneous tissue. We per-
PD-L1 expression was scored according to the guidelines of European formed a modified RNA extraction method from LCM FFPE tissue to
Thoracic Oncology Platform. recover sufficient RNA useful for subsequent RNA-sequencing (RNA-
Results: Low number of CD3, CD8, CD68 and PD-L1 positive TILs, and Seq) analysis.
loss of nuclear RAD51 (H-score ≤ .10) were associated with poor overall Methods: We isolated fibroblastic foci (FF) areas from tissue of 10 idi-
(OS) and progression free (PFS) survivals. Low tumoural PD-L1 was opathic pulmonary fibrosis (IPF) patients using LCM. Total microdissect-
associated with poor PFS in patients treated with neoadjuvant chemo-/ ed FF number/patient were 87 ± 33 with a mean total area of 396637,2 ±
radiotherapy (n=99). Multivariate analysis revealed that loss of RAD51 951131,6 μm2. RNA was extracted using an overnight lysis step followed
protein is an independent negative prognostic factor for PFS in training by incubation at 80°C for 15 minutes. RNA was preserved by adding
set (HR=1.8) and for PFS (HR=0.7) and OS (HR=0.7) in the validation RNase inhibitors at the end of the extraction procedure. Quality was
set. All p values are <0.05 evaluated with a 2100 Bioanalyzer Agilent 6000 pico kit. Libraries were
Conclusion: RAD51 immunohistochemical expression in tumour tissue obtained with the SMARTer Stranded Total RNA-Seq kit pico input
is a strong and independent prognostic factor in patients with resected mammalian of Takara Bio. Quality was expressed as DV200.
NSCLC and may complement PD-L1 and TIL for patients receiving Results: We successfully adapted a protocol to isolate RNA from small
immune checkpoint inhibitors. Further studies on RAD51 amounts of clinical LCM tissue samples. Using this approach, the mean
immunoexpression in patients with NSCLC is justified, particularly pa- quantity was 3181 ± 2502 pg/μl (mean±SD), ranging from 840 pg/μl to
tients receiving immunotherapy. 7530 pg/μl. Quality evaluation showed a mean value of 50.5% of DV200
(low-medium quality) ranging from 41% to 70%. Final libraries were
obtained with a 3.4-22.6 ng/μl quantity and a mean cDNA fragment
OFP-10-012 length of 289 nucleotides.
Copy number variation by NGS predict HER2 amplification status Conclusion: These data show that this protocol, optimised in our labora-
by ISH in NSCLC tory, lead to the extraction of adequate RNA samples from difficult and
H. Kivrak1, H. Özakıncı1, T. Baglan1, Y. Sahin1, S. Dizbay Sak1 limited FFPE tissues, in order to perform RNA-Seq analysis. The possi-
1
Ankara University, Turkey bility to study gene expression in specific cells/areas of FFPE tissue
represents an important issue for a better understanding of disease path-
Background & Objectives: HER2 amplification is found in 1-19% in ogenesis and for the identification of crucial biomarkers.
pulmonary adenocarcinomas and it is one of the mechanisms of acquired
resistance to first-generation tyrosine kinase inhibitors. We aimed to in-
vestigate the correlation of copy number variation (CNV) of HER2 gene OFP-10-014
by NGS, with immunohistochemical expression and amplification as de- Visceral pleural invasion by tumour size, cancer type and pathologist
termined by in-situ hybridization (ISH). in 1,560 resections
Methods: We investigated 13 cases showing CNV of HER2 gene by M. Bonert1, J. Cutz1, C. Finley1, I. El-Shinnawy1, S. Salama1, G. Gohla1,
NGS (GeneRead QIAact Lung DNA UMI Panel), HER2 protein overex- S. Alowami1, D. Lukic1, F. Tayyari2, R. Juergens3, A. Naqvi1
1
pression and amplification were evaluated by immunohistochemistry McMaster University and St. Joseph's Healthcare Hamilton, Canada,
2
(IHC) (clone 4B5) and silver ISH (INFORM HER2 Dual ISH DNA St. Joseph's Healthcare Hamilton, Canada, 3 McMaster University and
Probe) using HER2 testing guidelines for breast carcinoma. Hamilton Health Sciences, Canada
Results: HER2 CNV was detected in 7.8 % of our non-small cell lung
carcinoma (NSCLC) cases. Two of our cases showed additional patho- Background & Objectives: Visceral pleural invasion (VPI) is a poor
genic KRAS and EGFR mutations. Of the 8 cases that were evaluated by prognosticator in lung cancer and often upstages small tumours. We
IHC; 2,2,3 and 1 cases were scored as 0,+1,+2 and +3 respectively. sought to assess the VPI rate.
Unusual staining patterns (nuclear and/or cytoplasmic) were observed Methods: All resections at a thoracic centre for lung primaries
in 2 cases that were scored as 0. For the 7 cases that were evaluated by (accessioned between July 2012-Dec 2017) reported with a synoptic re-
SISH, HER2/CHR17 ratios ranged from 1.27 to 7; 4 cases being ≥2. In an port were retrieved and analysed. VPI rates were calculated by diagnosis
additional adenocarcinoma showing HER2 mutation (c.929C> T, and tumour size. Pathologist VPI rate variation was assessed with funnel
Virchows Arch

plots centred on the group median rate (GMR) and an in silico kappa
Tuesday, 10 September 2019, 17:15 - 19:15, Athéna
(ISK).
OFP-11 | Joint Session: Soft Tissue and Bone Pathology /
Results: The study period had 1,560 lung resections. 922 resections had
tumours <=3 cm and 279 (30%) of these had VPI. Overall, VPI was seen Infectious Diseases Pathology
in 11%, 27% and 40% of <=1, >1 & <=2 and >2 & <=3 cm lesions
respectively; 12%, 32% and 49% of adenocarcinomas (ADN) and 9%,
22% and 30% of squamous cell carcinomas (SCC). Eleven pathologists OFP-11-001
interpreted >40 resections (range: 41-298) and together saw 1,406. There Immunohistochemical and molecular analysis of NTRK-rearranged
were zero p < 0.001 pathologist outliers for tumours <=3 cm in relation to mesenchymal tumours
the GMR; however, 3 of 11 pathologists were (p < 0.001) outliers for the M. Le Quang1, J. Massiere2, A. Rullier1, V. Velasco3, J. Coindre3,4, F. Le
VPI rate in <=3 cm tumours. The ISK for VPI in all tumours/VPI in Loarer5,6
1
<=3 cm tumours was 0.63/0.60; this is better than for lymphovascular CHU Bordeaux, France, 2 INSERM U1812, Institut Bergoniè,
invasion present (0.56) but worse than the diagnosis of ADN (0.91) and Bordeaux, France, 3 Institut Bergoniè, France, 4 Universitè de
SCC (0.86). Bordeaux, France, 5 Department of Biopathology, Institut Bergonie,
Conclusion: VPI showed the expected variation by size and diagnosis. Bordeaux, France, 6 University of Bordeaux, Talence, France
Funnel plots and the ISK suggest that pathologist interpretation is a sig-
nificant factor and may be optimizable with statistical process control and Background & Objectives: Tropomyosin receptor kinases (Trk) can
judicious use of ancillary testing. be activated through activating translocations which may be targeted
with specific monoclonal antibodies. The family includes 3 trans-
membrane receptors (TRKA/C), involved in neural signalisation.
OFP-10-015 Translocations involving these genes can be found in many tumours
Interobserver variation in the classification of thymic lesions includ- but are mostly recurrent in mesenchymal tumours. No definitive
ing biopsies and resection specimens in an international digital mi- evidence is available regarding their morphological spectrum and
croscopy panel performance of immunohistochemistry. Therefore we systematically
J. Wolf1,2, H. Blaauwgeers3, A. Marx4, F. van Nederveen5, A.G. assessed a series of these lesions.
Nicholson6,7, A. Roden8, P. Ströbel9, W. Timens10, A. Weissferdt11, J. Methods: NTRK-rearranged tumours were retrieved from our archives
von der Thüsen2, M. den Bakker12 including 11 infantile fibrosarcomas, 41 biphenotypic sinonasal sarco-
1
Leiden University Medical Center, The Netherlands, 2 Erasmus Medical mas, 5 lipofibromatosis-like neural tumours, 9 conventionnal
Center, Rotterdam, The Netherlands, 3 Onze Lieve Vrouwen Gasthuis, lipofibromatosis, 1 high grade spindled sarcoma with neural phenotype,
Amsterdam, The Netherlands, 4 Universitätsklinikum Mannheim, 20 myofibromas/myofibromatosis. TRK expression was assessed with 2
Germany, 5 PAL Laboratory, Dordrecht, The Netherlands, 6 National pan-TRK (clones A7H6R and EPR17341); and 1 NTRK-C (clone
Heart and Lung Institute, Imperial College London, London, United C44H5)antibodies. Tumours were tested by FISH with NTRK1 break-
Kingdom, 7 Department of Histopathology, Royal Brompton & apart probes or whole RNA-sequencing (Truseq RNA exome, Illumina).
Harefield NHS Foundation Trust, London, United Kingdom, 8 Mayo Results: All but one tumour displayed low grade features. The high grade
Clinic, Rochester, USA, 9 Institute of Pathology, University Medical case was a spindled proliferation expressing S100 and CD34 in a 66yo
Center Göttingen, Germany, 10 University Medical Center Gronigen, adult. Pan TRK expression was diffuse in all but one NTRK1-rearranged
The Netherlands, 11 MD Anderson Cancer Center, Houston, USA, tumours (the high grade being negative). NTRK3-fused tumours were
12 mostly negative for both pan-TRK and TRK-C staining with 2 different
Maasstadziekenhuis, Rotterdam, The Netherlands
nuclear or cytoplasmic patterns of staining. Diffuse expression for TRK-
Background & Objectives: Thymic tumours are a rare entity in routine C was seen in all biphenoptypic sinonasal sarcomas despite absence of
pathology practice. Although the WHO classification describes a number underlying fusion. RNA-sequencing evidenced NTRK1 fusions with TPR
of well-defined categories, diagnosis remains challenging (n=1), TPM3 (n=1) and IRF2BP2 (n=1) in 5' and LMNA in 3' (n=2).
Methods: 332 tumours consisting of 98 biopsies and 234 resection spec- Conclusion: Pan-TRK immunostaining is highly sensitive to detect
imens were reviewed in a panel-based virtual microscopy approach by a NTRK1 but not NTRK3 rearrangements. Positivity may be seen in
group of 13 pathologists with expertise in thymic tumours over a period NTRK-wild type tumours, warranting molecular testing.
of six years. The specimens were classified according to the WHO clas-
sification. The data was subjected to statistical analysis and interobserver
concordance (Fleiss Kappa) was calculated. OFP-11-002
Results: The overall level of agreement was almost perfect Contribution of Raman Spectroscopy to diagnosis and grading of
(K=0.877) and differed slightly between the resection specimens chondrogenic tumours
(K=0.919) and the biopsies (K=0.777). By subclassifying R. Gaeta1, A. Franchi2, M. D'Acunto3, R. Capanna1
1
thymomas according to the ESMO Clinical Practice Guidelines University of Pisa, Italy, 2 Department of Translational Research and of
for diagnosis, treatment and follow up into groups including [B2, New Technologies in Medicine and Surgery, University of Pisa, Italy,
3
B3] vs [A, AB, B1] and [B3] vs [A, AB, B1, B2], the level of Institute of Biophysics, National Research Council, Pisa, Italy
agreement decreased slightly (K=0.792 and K=0.846 respectively).
The best agreements reached were in thymoma types A and AB. Background & Objectives: Raman Spectroscopy (RS) is a technique
Difficulties arose in distinguishing thymoma (especially A and B3) based on inelastic scattering of monochromatic light, usually a laser with
from thymic carcinoma. Within the thymoma subgroup difficulties wavelengths falling in the Ultraviolet-Visible-Near Infrared range. RS has
in distinction were seen within the B-group. demonstrated to be a label-free and non-destructive optical spectroscopy
Conclusion: Overall agreement of distinguishing mediastinal le- able to improve diagnostic accuracy in cancer diagnosis. We applied
sions was good when assessed by pathologists with experience Raman spectroscopy imaging in order to discriminate and grade cartilag-
in dealing with this rare tumour. Digital pathology facilitates ac- inous tumours.
cess to what is essentially a multinational resource. This platform Methods: The study group included three patients affected by
provides a template for dealing with rare tumours where expertise enchondroma (EC) and seven affected by chondrosarcoma (CS) (three
is sparse. grade 1, two grade 2 and two grade 3). We performed spectroscopy
 Virchows Arch

analyses with a Raman Imaging Microscope on formalin-fixed paraffin OFP-11-004

embedded unstained tumour tissue sections. Immunohistochemical analysis of 33 cases of chondroblastomas: a
Results: Several differences in the amino acid composition were single institutional experience from India
highlighted between the tumour types. In particular, the amount of β– B. Rekhi1, S. Ghate2, A. Shah2, M. Ramadwar3
1
Carotene progressively reduced from EC to high-grade CS, while the Department of Pathology, Tata Memorial Hospital, Mumbai, India,
2
degradation of collagen increased with the CS grade. Interestingly, Department of Surgical Pathology, Tata Memorial Hospital, Mumbai,
Linear Discrimination Analysis algorithm revealed major differences in India, 3 Tata Memorial Hospital, Mumbai, India
chemical composition between the group of EC-grade 1 CS and the group
of grade 2-grade 3 CS. Background & Objectives: Chondroblastoma is a relatively uncommon,
Conclusion: RS may be a useful tool in the histopathological analysis of primary benign bone tumour of young individuals; at times, fraught with
cartilaginous tumours since it provides biochemical information related to a diagnostic challenge, especially in differentiating it from a giant cell
tumourigenesis and progression of disease. Notably, the acquisition of a tumour; osteosarcoma and chondrosarcoma. Lately, few studies have
metastatic potential that characterises grade 2 and grade 3 CS was asso- shown the diagnostic utility of DOG1 in chondroblastomas. The present
ciated with a significantly different biochemical profile in comparison study was undertaken to evaluate immunohistochemical (IHC) expres-
with Grade 1 CS and EC, that are considered benign or locally aggressive sion of S100protein, DOG1 and p63 in 33 chondroblastomas.
tumours. Our results may contribute to improve diagnostic accuracy and Methods: From January 2013 to December 2018 (6-year duration), 104
reduce inter-observer variability in the assessment of chondrogenic tu- chondroblastomas were diagnosed with IHC staining, performed in 33
mours. cases. Conventional Hematoxylin and Eosin stained microsections and
IHC stained sections, in 33 cases were reviewed. The extent of IHC
staining of p63, S100 protein and DOG1 was classified as focal (staining
OFP-11-003 present in <50% of tumour cells) and diffuse (>50% of tumour cells).
Dedifferentiated liposarcoma with myxoid liposarcoma-like features Results: Seventy-four tumours occurred in males and 30 in females, with
and amplification of DNA damage-inducible transcript 3 (DDIT3) - age-range of 7-55 years(median=18.4), frequently in tibia (35/
an important diagnostic pitfall 104:33.65%), followed by femur, pelvis, calcaneum, talus, ribs, mandible
A. Szumera-Cieckiewicz1, O. Kuczkiewicz-Siemion2, P. Wisniewski2, A. and skull base. IHC staining for S100P was positive in 30/33cases (dif-
Wojnowska2, M. Grabowska-Kieryl2, K. Olszewska2, P. Rutkowski3, H. fuse in 18; focal in 12); DOG1 in 13/16cases (diffuse in 6; focally in 7)
Kosela-Paterczyk3, M. Prochorec-Sobieszek1 and p63 in 8/13cases (diffuse in 1; focal in 7). Sensitivity and specificity
1
Institute of Haematology and Transfusion Medicine, Diagnostic for S100P, DOG1and p63 in chondroblastomas was (90.9%, 59.3%);
Haematology Department, Poland, 2 Maria Sklodowska-Curie Institute (81.25%, 100%) and (64.3%, 46.6%), respectively.
- Oncology Center, Department of Pathology and Laboratory Medicine, Conclusion: S100 protein and DOG1 can be utilized for an objective
Poland, 3 Maria Sklodowska-Curie Institute - Oncology Center, diagnosis of a chondroblastoma, especially in diagnostic dilemmas, in
Department of Soft Tissue/Bone Sarcoma and Melanoma, Poland view of certain associated therapeutic implications.

Background & Objectives: Dedifferentiated liposarcoma (DDLSP)

is characterised by fusiform-cell-rich dedifferentiated fields OFP-11-005
coexisting with adipocyte-rich well-differentiated areas. A key fea- Superficial CD34+ fibroblastic tumour: clinicopathological, molecu-
ture of DDLSP is an amplification of 12q13-15 region, which lar and cytogenetic study of 4 cases
includes the MDM2 and DDIT3 gene. While MDM2 amplification R. Perret1, R. Carr2, J. Massière3, J.M. Coindre1,4, F. Le Loarer1,4
1
is considered a pathognomic feature of DDLSP, DDIT3 is typically Department of Biopathology, Institut Bergonie, Bordeaux, France,
2
rearranged in myxoid liposarcoma. Recent studied showed that Department of Histopathology, South Warwickshire NHS Foundation
DDIT3 amplification is associated with myxoid-like morphology Trust, Warwick Hospital, United Kingdom, 3 INSERM U1812, Institut
in DDLSP. The aim of our study was to present a case series of Bergoniè, Bordeaux, France, 4 University of Bordeaux, Talence, France
DDLSP with myxoid-like features harbouring both, MDM2 and
DDIT3 amplification. Background & Objectives: Superficial CD34+ Fibroblastic Tumour
Methods: Six cases of DDLSP with myxoid-like morphology were (SCFT) is a recently described soft tissue neoplasm of borderline malignan-
investigated pathologically, immunohistochemically and genetical- cy. To date fewer than 50 cases have been reported mainly concerning the
ly. Extended histopathological examination evaluated the presence clinical and histological features. Molecular studies have been rare, although
of homologous lipoblastic differentiation and round-cell compo- a single case had a t(2;5) chromosomal translocation. We describe the clin-
nent. Immunohistochemistry panel including MDM2 staining was icopathological, genomic and transcriptomic features of four new cases.
performed. Molecular analysis by fluorescence in situ hybridization Methods: Three cases were retrieved from the consultation files of the
was established to determine the status of MDM2 and DDIT3 Institut Bergonié (France) diagnosed in 2018-2019 and a further case
genes. came from Warwick Hospital (UK). Clinical data were obtained from
Results: The patients mean age was 63.5 (range from 44 to 85 the referring centers. Thorough histological examination was performed
years) with a 2:1 male to female ratio. Tumours were localized including immunohistochemistry. Array-Comparative genomic hybridi-
retroperitoneally (3) and extra-retroperitoneally (3). Morphologic zation (aCGH, Agilent platform, 8x60k array) and whole RNA sequenc-
features resembling pleomorphic liposarcoma were identified in ing (RNAseq, Illumina, Truseq-exome) was undertaken in 2 and 3 cases,
2/6 (33%) cases. No round-cell component was found. All the respectively.
cases demonstrated amplification of 12q15 and 12q13 regions con- Results: Patients were all males (age range 21 to 54 years). Tumours were
taining MDM2 and DDIT3 genes, respectively. No rearrangement located on the lower extremity (n=3) and shoulder (n=1). One case was a
of DDIT3 was observed. local recurrence. Histologically, all lesions were well circumscribed, com-
Conclusion: Our study demonstrates a correlation between DDIT3 am- posed of spindle and pleomorphic cells with low mitotic activity.
plification and specific morphologic features, which is the second original Tumours expressed CD34 (4/4), Pan-CK (3/4), Desmin (2/4) and
report in the literature. DIDT3-amplified DDLSP with areas resembling Androgen Receptor (2/3). aCGH genomic profiles were flat.
myxoid and pleomorphic liposarcoma may be misclassified as myxoid or Preliminary RNAseq results showed no translocations. One case had
pleomorphic liposarcoma. It is important to be aware of this potential mutations of FGFR1/TET2 and similar transcription profiles to
diagnostic pitfall. myxoinflammatory fibroblastic sarcoma.
Virchows Arch

Conclusion: In this study SCFT had consistent clinicopathological features Results: All MCC and 61% of ESFT were positive for INSM1. EMC,
with simple aCGH profiles. Although translocations were not seen and SFT, SS, GIST displayed INSM1 immunoreactivity in 70%, 21%, 2%
studies are still ongoing, RNAseq data showed novel FGFR1/TET2 muta- and 0.5% of the cases, respectively. Staining was diffuse in all MCC and
tions and transcriptomic resemblance with myxoinflammatory fibroblastic many ESFT and EMC but focal in SS, GIST and SFT. In ESFT, INSM1
sarcoma in one case. These results support the concept of SCFT as a distinct staining was not correlated with histological subtypes.
entity and expand the genomic characterization of this uncommon tumour. Conclusion: INSM1 expression in ESFT is higher than previously de-
scribed, nevertheless this finding does not distinguish these tumours from
other “small round cell tumours” (SRCT) such as MCC, EMC or SS that
OFP-11-006 may show focal or diffuse neuroendocrine differentiation. INSM1 immu-
Denosumab-treated giant cell tumours of bone: what happens in a noreactivity should be interpreted within a specific clinicopathological
short-middle term follow up? context, for instance strong and diffuse INSM1 expression in cutaneous
C. Fumagalli1, E. Chenu1, A. Sebio1, A. Peiró1, E. Moreno1, J. Llauger1, SRCT, strongly supports the possibility of MCC but in soft tissue/bone
I. Gracia1, S. Baguè1, R. Orellana1 tumours this immunoreactivity might prompt excluding the possibility of
1
Hospital de la Santa Creu i Sant Pau, Spain metastatic neuroendocrine tumour, EMC or ESFT.

Background & Objectives: Giant cell tumour of bone (GCTB) is a

locally aggressive tumour that most often affects epiphysis and OFP-11-008
epiphysometaphyseal areas of long bones in young to middle-aged adults. PD-L1 expression and immune related gene profile in giant cell tu-
Denosumab, a RANKL inhibitor, has been used as neoadjuvant therapy, mour of bone: an immunohistochemical and NanoString technology-
mostly in non-surgical cases. based study
Aims of this study are to evaluate the efficacy of preoperative Denosumab J. Metovic1, L. Annaratone2, A. Linari3, S. Osella-Abate2, C. Musuraca3,
therapy and the GCTBs’ changes and to document local recurrences after F. Veneziano3, C. Vignale3, L. Bertero2, P. Cassoni2, M. Papotti3
1
surgery. Departments of Oncology Pathology Unit University of Turin, Italy,
2
Methods: The cohort includes 23 patients (15females, 8males), median Department of Medical Sciences, University of Turin, Italy,
3
age: 37y-o. All patients underwent surgery after a median time of 11 Department of Oncology, University of Turin, Italy
months of Denosumab treatment (two cases developed adverse effects -
mandibular osteonecrosis- and stopped the treatment earlier). Background & Objectives: Giant cell tumour of bone (GCTB) is a rela-
Results: Anatomical locations of GCTB: lower extremity 13, upper ex- tively uncommon entity that, although in the vast majority of patients is
tremity 4, spine 1 and pelvis 3. Median size: 5,7 cm. All post-treatment presented as a benign disease, can develop local recurrences or progression.
surgical specimens showed histological changes related to Denosumab, Methods: A retrospective series of 70 cases including 46 GCTB and a
consisting of absence/reduction of giant cells, fibrosis, neoossification control group of 24 aneurysmal bone cysts (ABC) has been selected in
and lympho-histiocytic infiltration.One case showed pseudosarcomatous order to determine their immune-profile (PD-L1, CD4 expression,
change, and slight nuclear atypia was present in two biopsies.Two pa- together with Ki67 index) and immune-related gene expression profile
tients with R1 surgery had residual tumour.Three patients had local re- as detected by NanoString technology using nCounter PanCancer
currences. 78% of cases are free of disease after a median follow up of 18 Immune Profiling panel. The results were correlated with clinico-
months (1-104). pathological features.
Conclusion: The use of Denosumab has shown variable histological and Results: PD-L1 expression was detected in 13/46 (28.3%) GCTB and in
radiological responses, with worrisome histological changes in some only 1/24 (4.2%) ABC cases (p=0.017). The majority of GCTB (38/46;
cases THAT could lead to a misdiagnosis of malignancy. Despite the 82.6%) had an intense CD4 expression, in comparison to only 10/24
adverse effects, the use of Denosumab allows more conservative surgery (41.7%) ABC cases (p< 0.001). The mean Ki67 proliferation index of
and a low rate of recurrences. GCTB was 8.76 % (± 9.97), a significantly higher value than that of ABC
(3.54% ±5.38) (p=0.020). In the GCTB group, by univariate analysis,
PD-L1 expression was associated with a poorer disease free interval
OFP-11-007 (DFI) (HR=4.15, C.I 1.52-11.31; p=0.005). Also, Kaplan-Meier survival
INSM1 immunohistochemical expression in a large cohort of Ewing analysis supported these data: DFI was significantly longer in PD-L1
sarcoma family of tumours negative compared to positive cases (log-rank test p=0.0026).
A. Llombart-Bosch1, I. Machado2, J.A. López-Guerrero2, S. Navarro1, F. Furthermore, in PD-L1 positive lesions, three genes (CD27, CD6, IL10)
Giner3, P. Picci4 were significantly upregulated (p<0.01), while two others were down-
1
Pathology Department, University Valencia, Spain, 2 Instituto regulated (LCK and TLR8, showing borderline significance).
Valenciano de Oncología, Valencia, Spain, 3 Pathology Department, Conclusion: PD-L1 immunoexpression may help to select GCTB pa-
Universitary Hospital "La Fe", Valencia, Spain, 4 Pathology tients with higher risk of recurrence, who might potentially benefit from
Department, The Rizzoli Orthopaedics Institute, Bologna, Italy immune checkpoint blockade.

Background & Objectives: Insulinoma-associated protein 1(INSM1) is This work was partially supported by Fondazione per i tumouri muscolo
an emerging nuclear neuroendocrine marker. Its expression has been test- scheletrici-Torino grant. JM and LB are PhD fellows at the University of
ed in limited series of Ewing sarcoma family of tumours (ESFT). Given Turin.
the potential neuroendocrine differentiation in ESFT, we aimed to deter-
mine INSM1 expression in a large series of genetically-confirmed ESFT
and in a control cohort of tumours with well-known neuroendocrine OFP-11-009
differentiation or neoplasms with previously-reported neuroendocrine Histopathological findings in meningococcal infections as a cause of
expression. sudden-unexpected death
Methods: INSM1 immunohistochemistry on 433 ESFT, 54 Merkel cell A. Fernandez-Rodriguez1, B. Alves1,2, B. Morentin3, J. Arrieta3, M.R.
Carcinomas(MCC), 97 synovial sarcomas (SS), 28 Solitary fibrous tu- Mosquera1, B. Alcalá1, R. Abad1, M.P. Suárez-Mier1, I. Merino1,4
1
mour (SFT), 200 GIST and 13 extraskeletal myxoid chondrosarcomas Instituto Nacional de Toxicología y Ciencias Forenses, Madrid, Spain,
2
(EMC). Nuclear staining of moderate/strong intensity in at least 5% of University of Aveiro, Portugal, 3 Instituto Vasco de Medicina Legal,
tumour cells was considered positive. Vizcaya, Spain, 4 Hospital Clínico Universitario de Valladolid, Spain
 Virchows Arch

Background & Objectives: Meningococcal infection (MI) is a well- cells, mixed macrophage-monocytic and polymorphonuclear-
known cause of sudden-unexpected death (SUD) and post-mortem foren- neutrophilic infiltration.
sic analyses are often needed. Histopathological (HP) signs of a MI can be 2. To identify the etiological factor in the presence of the described chang-
diverse. The aim of this study was to determine the most frequent path- es, a comparison of clinical, anamnestic, serological and morphological
ological diagnosis in fatal cases of MI. data is necessary.
Methods: Twenty-eight cases of SUD due to MI in which microbiology
had been requested to our institution were revised. In all of them post-
mortem microbiology had confirmed the significant presence of OFP-11-011
N. meningitidis in sterile fluids and/or tissues. Microbiological and HP Validation of PCR for the diagnosis of leprosy in patients from
findings of the different tissues analysed were revised to assess the organs Kiribas
most commonly affected by MI. J. Gardner1, E. Towbridge1, S. Chambers1, T. Anderson1
1
Results: The most frequent organs studied were the heart and the Canterbury district health board, New Zealand
lung (93%), followed by the liver (89%), while brain was not so
common (75%). The most frequent diagnosis (61%) were signs of Background & Objectives: A New Zealand team of infectious disease
sepsis/septic shock (SS), followed by bilateral adrenal haemorrhage physicians have been assessing and treating patients with leprosy on a
(BAH), myocarditis, and DIC (57%, 46%, and 43% respectively). remote island nation in the Pacific Ocean called Kiribas. This project
BAH presented with SS in 39% cases, and with DIC in 32%, while commenced in 2016 and to date 45 patients have been studied.
myocarditis was present with SS in 36%. In 3 cases all 4 diagnosis The main objective of this study was to validate the use of PCR for
(SS, BAH, DIX and myocarditis) were present. Meningitis was diagnosis and compare it against traditional histology and labour-
found only in 6 cases (21%). intensive ZN staining.
Conclusion: The main form of fatal MI was sepsis/septic shock, often Methods: Patients identified as having probable leprosy had matching
associated with BAH. Neurological affectation wasn’t common, but the punch biopsies of lesional skin tissue submitted for histology and modi-
heart was often affected. It is necessary to include brain/meningeal, heart, fied ZN staining with a separate biopsy submitted in ethanol for PCR
liver, and adrenal tissue in the HP study of SUD, in order to search for MI PCR was set up specifically for this project and histology was used to
as a possible cause of death. validate it.
Results: In all cases of both lepromatous and tuberculoid leprosy the PCR
confirmed the diagnosis with read numbers ranging from 15 to 38.
OFP-11-010 Additional cases of borderline histology with no acid-fast bacilli seen on
Peculiarities of morphological verification of bacillary angiomatosis histology but a clinical diagnosis of leprosy were able to be diagnosed by
A. Mustafina1 PCR alone!
1
Medical University of Karaganda, Kazakhstan The validation was successful.
Conclusion: In third world countries without easy access to histology
Background & Objectives: The damaging effect of Bartonella henselae PCR alone can be a stand-alone diagnostic test for this Important disease.
can lead to different variants of the infection process, in particular in
patients with a compromised immune system, to a multifocal
angioproliferative reaction (bacillary angiomatosis). OFP-11-012
Pathomorphological changes in bacillary angiomatosis are well de- In-situ protein expression analysis of cancer testis antigen SSX2
scribed. At the same time, the lack of anamnestic, clinical data and alert- A. Jungbluth1, D. Frosina1, C. Lezcano1, J. Geronimo1, E. Hernandez1,
ness at the pathologist, as well as the similarity with a number of other K. Busam1
1
pathological processes often lead to difficulties in histological verification Memorial Sloan Kettering Cancer Center, USA
of this disease. The purpose of the study- a retrospective analysis of
biopsy material to improve the quality of diagnosis of Bartonella Background & Objectives: CT antigens (CTAs) such as NY-ESO-1 and
infection. MAGE are expressed in various malignancies and in normal tissues al-
Methods: The analysis of 28 cases of a skin biopsy from the archival most exclusively in testis. CTAs are highly immunogenic and due to their
material of the pathological-anatomical centre in Central Kazakhstan for tumour-associated expression pattern, are employed as vaccine targets for
2016-2018, in which the histological conclusion included a description of cancer immunotherapy. SSX2 is another CTA which was identified by its
lymphadenitis without mentioning the etiological factor (lymph nodes) or involvement in t(X;18) translocation in synovial sarcoma. On an mRNA
the pathological conclusion was descriptive (lymph nodes and skin). level, SSX2 is expressed in various malignant neoplasms. However, little
Retrospective diagnosis of bartonellosis was performed by indirect is known about the in-situ protein expression of SSX2.
immuno-fluorescence reaction in order to detect the B. henselae particu- Methods: A novel anti-SSX2 monoclonal antibody (mAb) CL3202
late antigen or antibodies to it. (Sigma; AMAb91141) was identified and tested for specificity using
Results: In the analysis of 28 cases of skin biopsy in 3 patients were FFPE tissues and cell line pellets with known SSX2 mRNA expression
Bartonella in the form of clusters in close proximity to endothelial cells. pattern. CL3202 worked best at 0.5ug/ml using heat induced antigen
Thus, 3 cases of bacillary angiomatosis were selected in which the etiol- retrieval employing pH8 buffer for 30’. All assays were performed on
ogy of the pathological process was confirmed by an indirect immuno- an automated stainer platform (Leica Bond-3). Various malignancies were
fluorescence reaction. In the analysed cases of vascular changes during tested by IHC such as melanomas, as well as panels of carcinomas and
skin biopsy, the histological pattern is characterised by angioproliferative sarcomas.
lesions with the presence of proliferating endothelial cells, mixed Results: More than 250 tumours were analysed. SSX2 was highly
macrophage-monocytic and polymorphonuclear neutrophilic infiltration. (100%) expressed in synovial sarcoma displaying a homogeneous ex-
In each of the selected cases, a focal proliferation of microcapillaries pression in all tumours. Melanoma showed the second highest incidence
delimited by enlarged convex, cubic or polygonal widely cytoplasmic of SSX2-positivity in 23% followed by squamous cell carcinoma of the
endothelial cells, with or without signs of cytological atypia, is detected. lung (5%) being only heterogeneously expressed in parts of the tumour.
Inflammatory infiltration is mixed (lymphocytic neurophilic) with All other carcinomas (liver, ovary, lung (adeno), kidney, colorectum)
leukocytoclysis and focal necrosis. were SSX2 negative. A wide variety of sarcomas (osteo-, leimyo-,
Conclusion: 1. Bacillary angiomatosis is characterised by chondro-, lipo-sarcoma) as well as mesothelioma and seminoma were
angioproliferative changes with the presence of proliferating endothelial all SSX2 negative!
Virchows Arch

1
Conclusion: This is the first comprehensive analysis of SSX2 pro- Dokuz Eylul University Faculty of Medicine, Department of Pathology,
tein expression. SSX2 is homogeneously expressed in 100% sy- Turkey, 2 Altinbas University School of Medicine, Turkey, 3 Dokuz Eylul
novial sarcoma. Expression in other tumours is considerably less University Faculty of Medicine, Department of Paediatric Oncology,
and most prevalent in melanoma. SSX2 expression vastly differs Turkey, 4 Dokuz Eylul University School of Medicine, Turkey
from CTAs such as MAGE, NY-ESO1 and CT7. Due to its ex-
pression pattern, SSX2 may be a valuable vaccine target and/or Background & Objectives: Langerhans cell histiocytosis (LCH) is a rare
diagnostic tool in synovial sarcoma. disease presenting with usually a localized disease but sometimes a wide-
spread aggressive disorder especially in children. Among the somatic
mutations in RAF-MEK-ERK pathway, especially BRAF mutation has
Tuesday, 10 September 2019, 17:15 - 19:15, Thalie
been detected so far in LCH. We aimed in this study to investigate the
OFP-12 | Paediatric and Perinatal Pathology prognostic significance of the mutations of target genes playing a role in
the RAF-MEK-ERK pathway in paediatric LCH.
Methods: Mutation analyses were performed on tumour DNA extracted
OFP-12-001
from formalin fixed paraffin embedded biopsy specimens of 38 paediatric
Renal cell carcinoma in children and adolescent, a retrospective anal-
LCH cases using a direct sequencing technique for BRAF, ARAF,
ysis of a cooperative European cohort
MAP2K1 and MAP3K1 genes. The mutational status was correlated sta-
T. Denize1, S. Massa2, C. Vokuhl3, A. Valent4, A. Testi2, L. Dainese1, L.
tistically with survival, clinical progression (disease relapse), and the
Militti5, E. Thebaud6, R. Furtwaengler7, K. Pritchard-Jones8, N. Graf7, F.
established clinical prognostic parameters of LCH such as age, gender,
Spreafico9, A. Verschuur10, G. Vujanic11, P. Collini2, A. Coulomb1
1 localization, multisystem disease, central nervous system risk lesions, and
Sorbonne University, APHP6, Pathology department, Armand Trousseau
risk organ or special site involvement.
Hospital, Paris, France, 2 Diagnostic Pathology and Laboratory Medicine
Results: BRAF V600E mutation was detected in 14 cases (36.8%) where-
Department, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan,
as ARAF mutation was found in only one case. No mutations were iden-
Italy, 3 Kiel Paediatric Tumour Registry, Department of Paediatric
tified for MAP2K1 and MAP3K1 genes. The association of BRAF V600E
Pathology, University Schleswig-Holstein, Germany, 4 Institute Gustave
mutation was significant in children with multisystemic disease, younger
Roussy, biology and medical pathology department, Villejuif, France,
5 age (< 2 years), skin and special organ involvement. BRAF V600E mu-
Dip. Medicina di Laboratorio e Biotecnologie Diagnostiche U.O.C.
tation was an independent predictive parameter for disease relapse.
Anatomia Patologica ASST Ovest Milanese - Ospedale di Legnano, Italy,
6 Conclusion: We therefore conclude that BRAF V600E mutation may be a
Paediatric oncology derpartment, CHU Nantes, France, 7 Saarland
significant marker for predicting disease progression in LCH and a can-
University, Paediatric Oncology & Haematology, Homburg, Germany,
8 didate for targeted therapy for children with disease relapse and
University College London UCL, Developmental Biology and Cancer,
multisystemic disease.
London, United Kingdom, 9 Paediatric Oncology Unit, Fondazione
IRCCS Istituto Nazionale dei Tumouri, Milan, Italy, 10 Paediatric oncology
Dokuz Eylul University’s Research Trust and Turkish Paediatric
and haematology department, La Timone Hospital, Marseille, France,
11 Oncology Group
Weill Cornel Medicine, Department of Pathology, Sidra Medicine,
Doha, Qatar
OFP-12-003
Background & Objectives: Renal cell carcinomas (RCC) are rare in
Histopathology of Steel syndrome due to new pathogenic variants of
children and adolescent, accounting for less than 4% of kidney tu-
COL27A1 gene
mours. In order to get insight into their pathological characteristics,
A. Nadal1, G. Frigola2, O. Gómez3, V. Borobio3, A. Vallmajó4, R. Oliva5,
we analysed a large cooperative European cohort focusing on epide-
M. Pauta3, A. Borrell3
miology, histological subtype, immunophenotype, and TFE3/TFEB 1
Pathology Department, Biomedical Diagnostic Center (CDB), Hospital
status by FISH.
Clinic de Barcelona, IDIBAPS, Spain, 2 Pathology Department,
Methods: Cases collected from the French, Italian, German and British
Biomedical Diagnostic Center (CDB), Hospital Clinic of Barcelona,
pathological databases were reviewed. TFE3-FISH analysis was per-
Spain, 3 BCNatal, Hospital Clínic, IDIBAPS, Barcelona, Spain,
formed on all cases and TFEB-FISH when morphology was suggestive. 4
Quantitative Genomic Medicine Laboratories, S.L., qGenomics,
A wide immunohistochemical panel was performed.
Esplugues de Llobregat, Spain, 5 Biochemistry and Molecular
Results: We collected 159 cases. Median age at diagnosis was 11 years
genetics,Hospital Clínic, IDIBAPS, Barcelona, Spain
(9m-18y) with a slight male predominance (1,1:1). Median tumour size was
6 cm. The most frequent histotype was MiT-family translocation RCC
Background & Objectives: Steel syndrome (STLS) was described in
(MiTRCC) in 42%. Non-MiTRCC included papillary RCC type 1 (12%)
1993. 37 cases are reported in the literature. Patients show characteristic
and 2 (14%), chromophobe RCC (4%), adult clear cell RCC (3%), SDHB-
facies, dwarfness, irreducible bilateral hip and radial head dislocation, and
associated RCC (1%), medullary/CDC RCC (3%), RCC associated with
carpal bone coalition. COL27A1 gene (9q32) mutations were recently
neuroblastoma (1%) and unclassified RCC (22%). In the MiTRCC, median
described in the pathogenesis of the syndrome.
age was 9y with a female predominance (sex ratio 1:1.7) whereas in the
Methods: Two consecutive pregnancies in a nonconsanguineous couple
non-MiTRCC group, children were younger (mean 8y).
were interrupted at 22 and 17 weeks of gestational age because of severe
Conclusion: MiTRCC is the most common RCC histological subtype in
US scan anomalies. Complete autopsies with microscopic exam were done
children and adolescents, affecting more frequently girls, with frequent
on both fetuses. Next-generation-based clinical exome sequencing was ap-
LN metastasis. TFE3-FISH analysis is the gold standard for MiTRCC
plied to the first fetus. Exome sequencing results, parental segregation, and
diagnosis and should be systemically performed. NGS analysis is ongo-
affection of the second fetus were confirmed by Sanger sequencing.
ing on non-MiTRCC in order to better classify this heterogeneous group.
Results: Both fetuses had short long bones, dysmorphic oval shaped
facies with hypertelorism, absent humeral capitulum with flattened radial
heads, and carpal bone coalition. The first fetus had deformities of both
OFP-12-002
the femoral head and the acetabulum, the second one and an overt hip
BRAF V600E mutation: a significant biomarker for prediction of
dislocation. Histologically, proliferative metaphyseal cartilage showed
disease in paediatric Langerhans cell histiocytosis
retardation and disorganization. Resting cartilage was hypercellular, or-
E. Özer1, A. Sevinc2, D. Ince3, R. Yuzuguldu4, N. Olgun3
ganized in irregular nests limited by acellular matrix. Two previously
 Virchows Arch

unreported variants in COL27A1 gene (c.2548G>A -p.Gly850Arg- and Methods: The study group consisted of 45 women and their children,
c.3249 +1G>T -affecting the canonical splicing site of exon 29-) were born as a result of the programs of donation of oocytes and “Surrogate
found in both fetuses in compound heterozygosis with parental mendelian motherhood”. HLA typing was performed in maternal and cord blood
segregation. Each parent carried one of the mutations in heterozygosis. samples after delivery. HLA-DNA-TEH reagent kits were used for typing
Mutation pathogenicity was confirmed in silico. genes of the main human histocompatibility complex (HLA) class II
Conclusion: This is the first report to include histology of STLS. The (DQA1, DQB1 and DRB1) by the polymerase chain reaction (DNA
COL27A1 gene variants here described increase the number of mutations technology, Russia). The obtained results were processed using the
associated with STLS. Parental segregation indicates autosomal recessive SPSS Statistics for Windows statistical software package (USA).
inheritance. Results: In this work, a number of alleles with a protective effect (DQA1
* 0102, DQB1 * 0302, DRB1 * 13, etc.) were identified, with which in
This work was partly funded by grant from FIS PI17/01153, Instituto de the genotype the probability of developing hypertensive pregnancy com-
Salud Carlos III, Ministerio de economía y competitividad, Spain. plications (gestational arterial hypertension, PONRP, pre-eclampsia) was
significantly lower (p <0.01). In both mothers and children, protective
alleles were detected, in the presence of which we observed a decrease in
OFP-12-004 the number of complications. We identified 8 protective alleles in
Features of PLAP expression in placental structures during allogeneic mothers, and 7 in children.
pregnancy (surrogate maternity, oocyte donation) on the background of Conclusion: In our work, we did not get convincing results indicating the
preeclampsia, as an indicator of exosomal trophoblast activity role of the inconsistency in the HLA system in the development of ob-
E. Rudenko1, E. Kogan1, T. Demura1, N. Zharkov1, N. Trifonova1 stetric complications during pregnancy with an allogeneic fetus. In the
1
I.M. Sechenov First Moscow State Medical University (Sechenov blood of the mother and fetus, a number of protective alleles were iden-
University), Russia tified, in the presence of which the probability of developing hypertensive
complications was deliberately lower.
Background & Objectives: PLAP - placental alkaline phosphatase spe-
cific for the isolation of exosomes (vesicles up to 100 nm in size, con-
taining miRNA and siRNA), of placental origin. PLAP-positive OFP-12-006
exosomes can be detected in the mother’s blood already in the first tri- New data about telocytes of placental villi
mester of pregnancy, their number increases during the process of matu- N. Nizyaeva1, T.V. Sukhacheva2, M.N. Nagovitsyna1, R.A. Serov2, N.E.
ration of the fetus and reaches its maximum at the time of delivery. The Kan1, A.I. Shcheogolev1
1
change in the profile of exosomes during various complications of preg- V.I.Kulakov National Research Center for Obstetrics, Gynaecology and
nancy, including the development of preeclampsia, is shown. Perinatology of Ministry of Healthcare of the Russian Federation,
Methods: The placental material and placental biopsy from 48 women Moscow, Russia, 2 A.N.Bakoulev Scientific Center for Cardiovascular
who were pregnant as a result of in vitro fertilization, divided into 2 Surgery, Moscow, Russia
groups, were studied. The first group included 32 women after allogeneic
pregnancy. Subgroups were formed on the basis of the presence or ab- Background & Objectives: is analysis of morphological features of
sence of pre-eclampsia. An immunohistochemical study using primary telocytes in placenta villi in preeclampsia (PE).
antibodies used mouse anti-PLAP (Dako,1: 200). Detection of exosomes Methods: Groups of study included 37 patients of reproductive age, 25-
in the cytoplasm of trophoblast cells and brush border of the 39 weeks of gestation: 22 patients with PE and 10 with uncomplicated
syncytiotrophoblast was carried out using electron microscopy. full-term pregnancy (UP). We performed histological (hem&eosin) and
Results: PLAP expression was established in the apical part of the villi, immunohistochemistry studies on the paraffin-embedded slices of placen-
the parietal trophoblast, as well as for singl cells of the EVTs of the ta, taking after cesarean section, using primary antibodies to CD117,
placental bed. Giant multinucleated trophoblast cells were negative. The CD34, vimentin, including the new marker for telocytes TMEM16a
optical density staining for the syncytiotrophoblast chorionic villus was (DOG-1). Besides, 15 placental samples were examined using electron
calculated. A significant decrease in the expression of the optical density microscope «Philips CM100».
of PLAP in STB was shown against the background of preeclampsia. Аn Results: TC in placenta in UP group were characterised by vimentin+,
electron microscopy study confirmed the coincidence of PLAP localiza- week СD117+, CD34+. We revealed TMEM16a+ in stem and interme-
tion in exosomal structures. diate villi in UP group, but in PE we observed TMEM16a expression
Conclusion: The relationship between the decrease in expression of weakening. Electron microscopy examination of placental samples in UP
PLAP and the number of placental exosomes in the pathogenesis of has been found TC in different villi types. Ultrastructural characteristics
pre-eclampsia during allogeneic pregnancy has been established. of TC indicated their heterogeneity and presence of at least three cell
types. In PE telocyte in the stroma of intermediate villi acquired charac-
teristics of fibroblasts and fibrocytes, while collagen deposition in the
OFP-12-005 villous stroma led to abnormal angiogenesis.
The study of polymorphism of HLA genes as a predictor of the de- Conclusion: Thus, the heterogenetic telocytes population with different
velopment of hypertensive complications of pregnancy immunophenotypes and ultrastructural characteristics was revealed in vari-
E. Rudenko1, E. Kogan1, T. Demura1, N. Trifonova1 ous sites of placenta, they are possibly associated to different functions.
1
I.M. Sechenov First Moscow State Medical University (Sechenov
University), Russia Supported by the Grant of the President for leading scientific schools
(NS-4566.2018.7, Agreement 075-02-2018-519).
Background & Objectives: After the first successful use of donor oo-
cytes in 1984, the number of assisted reproductive technology cycles
using donor eggs in the US and Europe continues to grow. Alogenic OFP-12-007
pregnancy is associated with a high risk of developing complications, Perinatal acute respiratory failure: autopsy remains the best quality
especially hypertensive ones. Allogeneic pregnancy is characterised by control tool
a high degree of discrepancy in the HLA system. It is promising to study E. Castro1, N.M. Patil1, E. Popek1
1
the polymorphism of HLA system genes as a molecular predictor of the Pavilion for Women, Texas Children's Hospital, Baylor College of
development of hypertensive complications. Medicine, USA
Virchows Arch

Background & Objectives: Clinically, acute respiratory failure is one of Background & Objectives: To evaluate the spectrum of cardiac anom-
the most common problems seen in premature and term babies. The alies found in fetal autopsies in correlation with chromosomal
etiology varies from surfactant deficiency in premature babies, to aneuploidies.
meconium-aspiration syndrome (MAS), sepsis, pulmonary hypoplasia Methods: Retrospective review of 296 fetal autopsies performed at
and hypertension in term babies. Autopsy examination of the fetus is an CHLO during 2018. 54 cases with chromosomal abnormalities confirmed
important quality control, and often establishes the etiology of perinatal by karyotyping (20 males, 31 females and 1 undefined sex) were retrieved
respiratory depression. The aim of this study was to correlate autopsy and analysed for presence and classification of cardiac anomalies. Cases
findings with clinical impression in cases of failure to resuscitate in early were assigned to main categories of cardiac defects, and the most com-
neonatal period. mon associations were determined.
Methods: We reviewed 200 autopsy reports from 2000-2019 at our in- Results: Median maternal age was 37 years-old(range:22-48) and ges-
stitution. Inclusion criteria were age (0-10 days) and clinical history of tational age 18 weeks (range:13-34). Most common aneuploidy was
respiratory failure. Correlation of agreement between clinical and final trisomy21 (57%), followed by trisomy18(24%), X monosomy (13%),
autopsy diagnoses was calculated. Cases with imaging autopsy only were trisomy13 (4%) and triploidy (2%). Abnormal cardiac findings were
excluded. identified in 32 fetuses (59%). Termination of pregnancy was per-
Results: Infection was the leading etiology for perinatal respiratory fail- formed in 45 cases (83%) with the other 9 (17%) resulting from spon-
ure (25% of cases), followed by lethal complex malformations (15%), taneous fetal demise. Most common malformations in trisomy21 were
placental causes (14%) and complex congenital heart disease (12%). septal defects (26%), in trisomy18 Tetralogy of Fallot (38%) and in X
Other etiologies included congenital diaphragmatic hernia and lung hy- monosomy left ventricular outflow tract obstructions (LVOTO;43%).
poplasia, cord accident, hemorrhage due to visceral rupture, non-immune Both cases of trisomy13 presented with LVOTO. A complex anomaly
hydrops, MAS, metabolic diseases, neoplasia and complications of pre- was found in the triploidy case.
maturity. There was concordance between clinical and autopsy diagnoses Conclusion: Spontaneous fetal demise and termination of pregnan-
in 45% of cases. The most frequent unexpected diagnosis was infection cy due to unbalanced chromosomal abnormalities are frequent and
(23%). associated with multiple congen ital anomalies. Cardiac
Conclusion: The number of autopsy examination requests in the hospital malformations are the most common alterations found. Our cohort
setting have been declining worldwide. Our findings underscore the im- presents lower frequency of cardiac defects comparing to the liter-
portance of autopsy examination as a quality control tool for early neo- ature, and brings to attention the complexity and variability of
natal deaths. phenotypic expression of aneuploidies.

OFP-12-008 OFP-12-010
Body stalk anomaly: a rare lethal fetal anomaly, rarely reported in a Stillbirth and perinatal death: a retrospective study with application
dichorionic diamniotic twin pregnancy of ICD-PM to the autopsies performed between 2007 and 2018 in
R. Castiglione1, K. Baltz-Ghahremanpour1, A. Bosse1 Coimbra
1
Klinikum Stuttgart - Institute of Pathology, Germany A. Lai1, F. Ramalhosa1, M.B. Pimentão1, C. Faria1, V. Almeida1, H.
Moreira1, R. Almeida1, J. Fraga1, O. Caetano1, C. Cerdeira1, R. Pina1
1
Background & Objectives: Body stalk anomaly (BSA) is the rarest, Centro Hospitalar e Universitário de Coimbra, Portugal
invariably lethal abdominal wall defect and may be associated to various
abnormalities of neural tube and internal organs. It is characterised by a Background & Objectives: Accordingly, with the estimates of WHO in
lack of development of abdominal wall: the abdominal organs lie exter- 2016, each year occurs 2.6 million of stillbirths, with more than 95%
nally in a sac of amnioperitoneum. The fetus is attached directly to the taking place in low and middle-income countries. With the aim of reduce
placenta by lack of or very short umbilical cord. BSA is rarely reported this mortality rate, the WHO released an action plan and recommends the
during twin pregnancy. It is generally not associated to genetic use of ICD-PM (International Classification of Diseases – Perinatal
abnormalities. Mortality) for international reporting of stillbirths and perinatal deaths.
Methods: Here we present the case of an BSA-affected male patient died Portugal has one of the best perinatal mortality rate with 3,90 in 2016, but
100 minutes after full-term birth in a context of dichorionic-diamniotic it is still possible to improve with the identification of the main change-
twin pregnancy. His twin brother showed no anomality of any sort. The able causes: maternal or health care.
mother was a healthy primipara without significant family history. Prior Methods: In order to identify the main causes of stillbirth (>22weeks)
to autopsy, a radiological examination was performed. and perinatal deaths, we retrospectively reviewed the stillbirths and peri-
Results: Macroscopic evaluation revealed a total lack of development of natal autopsies performed in Centro Hospitalar e Universitário de
the abdominal wall and an incomplete, asymmetric development of the Coimbra, in 2007 and 2018 years (not including medical termination of
thorax wall. Liver, bowel, pancreas and spleen was located in extrafetal pregnancy).
coelom. Only one kidney was available. Anal atresia was reported. Results: From a total of 183 stillbirths and perinatal autopsies, 107(58%)
Skeletal examination revealed a severe scoliosis and a rudimental, dorsal were male, 74(40%) female and 3(1,6%) undetermined. The median gesta-
deviated left leg. No pathological finding were detected during the exam- tional age was 29weeks (range 22-41weeks), the median neonatal period was
ination of the skull and upper extremities. A 1,5 cm short umbilical cord 1,5days and the median maternal age was 31years (range 16-45).
was documented at placenta examination. The histological examinations From the 82cases (45%) of antepartum death, 37 cases(45%) were due to
revealed no further alterations in the maturation of the organs. “A3 – Acute antepartum event”. In the category of intrapartum death, we had
Conclusion: BSA is a very rare, fatal disease. Here we documented a 77 cases (42%) were the major cause was “I3 – Acute intrapartum event” (35
case of BSA in the extremely rare context of twin pregnancy, which cases-46%). In the neonatal death, we had 24 cases(13%), in which the “N7 –
represents a big challenge in the clinical management. Respiratory and cardiovascular disorders” were the commonest cause (9
cases-37,5%). In addition, the mother conditions more frequent was “M1 –
Complications of placenta, cord and membranes (126 cases-69%).
OFP-12-009 Conclusion: Despite our good perinatal mortality rate there is still some
Cardiac defects in fetal postmortem examinations with aneuploidy aspects that we can improve in medical care, public health and population
M. Farinha1, L. Monteiro2 education to achieve better assistance to pregnant women, their babies
1
IPO-Porto, Portugal, 2 CLHO, Portugal and their families.
 Virchows Arch

OFP-12-011
Tuesday, 10 September 2019, 17:15 - 19:15, Erato
Metabolic reprogramming and altered isotope fractionation of can-
OFP-13 | Joint Session: Molecular Pathology / Haematopathology
cerous cells of neural origin in the light of advanced atomic level mass
spectrometry
K. Taran1, P. Paneth2 OFP-13-001
1
Medical University of Lodz, Poland, 2 Lodz University of Technology, Expression of SOX11 in mantle cell lymphoma is associated with
Poland increased angiogenesis and immunosuppressive microenvironment
L. Veloza1, P. Balsas2, I. Ribera-Cortada3, A. Martinez1, V. Amador2, E.
Background & Objectives: Isotope Ratio Mass Spectrometry advanced Campo1
approach has been recently proved to be applicable to cancer biomarkers 1
Hospital Clinic, Spain, 2 Institut d'Investigacions Biomèdiques August Pi i
research. The method for the first time alights structural mechanisms of Sunyer (IDIBAPS), Spain, 3 Hospital Nostra Senyora de Meritxell, Andorra
fundamental cancer cell biology. Most of isotope effects associated with
biosythesis and metabolism exhibit different values depending of partic- Background & Objectives: The role of immune cells and angiogenesis
ular mechanisms of reactions that take place. The anaplerotic pathway in the clinical behaviour of mantle cell lymphoma (MCL) is not fully
glutamin metabolism is known to be unregulated in many cancer cells. In understood. Therefore, the objective of this study was to characterise
neuroblastoma biology glutamin is known to be necessary for the survival the tumour microenvironment, correlate with SOX11 expression and
regardless of ATP acquisition. overall survival (OS).
Methods: There was performed a search for light isotope profiles of Methods: This study included 53 MCL (23 spleens:15 SOX11− and
tumour cells and tissues from tumour surrounding in complete spectrum 8 SOX11+ and 30 lymph nodes: 6 SOX11− and 24 SOX11+).
of neuroblastoma group with the use of a Sercon Continuous 20-22 Flow Angiogenesis was evaluated by analysing the intratumoural micro-
Isotope Ratio Mass Spectrometer coupled with an Elemental Analyser for vascular area (MVA) and microvascular density (MVD) by anti-
simultaneous light isotopes estimation. CD34 immunohistochemistry. The T-cell infiltrate was studied by
Results: Obtained changes in isotopic signatures of light isotopes in immunohistochemistry by counting CD3, CD4, CD8 and FOXP3+
transformed cells in relation to the established knowledge of cancer cell cells and calculating the mean value of five representative
isotopic profiles and metabolism confirm the metabolic reprogramming intratumoural areas (40x magnification).
of tranformed cells and indicates that glutamin can become the major Results: SOX11+ MCL showed an increased angiogenesis than
source of lipogenic acetylo-CoA through reductive carboxylation. SOX11− (median MVA: 14.6 x10 -3 vs 5.0 x10-3 p<0.001, median
Conclusion: The IRMS method looks beyond traditional meanings of MVD: 18.8/μm2 vs 14.2/μm2, p=0.016). Cases with a high MVD
cancer investigation and confirm metabolic reprogramming by promoting and MVA presented a shorter OS (p=0.004 and p=0.064 respective-
lipolysis in the transformed neural cells from neuroblastoma group. ly). In nodal MCL, SOX11+ cases presented fewer CD3+ T-cells
(48 ±SD 27 vs 88 ±SD 31, p=0.002) and CD4+ T-cells (18 ± SD 10
vs 65 ±SD 33, p<0.001), and a lower CD4/CD8 ratio (0.9 ±SD 0.3
OFP-12-012 vs 2.7 ±SD 1.1, p<0.001). SOX11+ cases showed more Tregs
Vascular anastomoses in monochorionic twin placentas: a (FOXP3+) (12 ±SD 9 vs 6 ±SD 4, p=0.07) and a higher FOXP3/
pathomorphological study using CT CD3 ratio (0.2 ±SD 0.1 vs 0.06 ±SD 0.02, p<0.001), which was
A. Shchegolev1, N. Тetruashvili1, U. Tumanova1, V. Lyapin1, A. associated with a shorter OS in nodal MCL (p=0.03).
Kozlova1, V. Bychenko1, V. Sakalo1, G. Sukhikh1 Conclusion: Our study suggests that SOX11 is associated with im-
1
NMRCOGP, Russia munosuppression and angiogenesis, contributing to the aggressive-
ness in MCL. Hence, the MCL microenvironment could represent a
Background & Objectives: The use of CT in the placental studies can potential therapeutic target.
effectively identify and evaluate all vascular anastomoses.
Objective: to study of anastomoses in monochorionic diamniotic pla-
centas at fetal growth retardation (FGR). OFP-13-002
14 monochorionic diamniotic twin placentas were studied. Group-I - 7 Prognostic role of the microenvironment in follicular lymphoma
placentas with FGR. Group-II - 7 placentas without FGR. treated with Rituximab and Rituximab+lenalidomide - results of a
Methods: Conducted a phased macroscopic and CT examinations of the translational study of the SAKK35/10 trial
placental vessels using contrast-coloring mixtures of 4 colors. The mix- T. Menter1, A. Tzankov2, E. Zucca3, E. Kimby4, S. Hayoz5, S. Dirnhofer2
ture consisted of a dye and radiopaque substance in exactly calculated 1
Institut für Medizinische Genetik und Pathologie, Universitätsspital
concentration. After catheterization of the vessels of both umbilical cords, Basel, Switzerland, 2 University Hospital Basel, Switzerland,
the mixture was introduced stepwise. CT and visual assessment were 3
Oncology Institute of Southern Switzerland, Switzerland,
performed at each stage. 3D reconstructions and color mapping of CT- 4
Department of Medicine at Huddinge, Karolinska Institutet, Sweden,
tomograms was performed. The presence of anastomoses, their type, 5
SAKK Coordinating Center, Switzerland
diameter and branching order were determined.
Results: In Group-I vascular anastomoses in the placenta were detected in Background & Objectives: Follicular lymphoma (FL) constitutes a
85.71%, and in Group-II in 57.14%. In Group-II 1 anastomosis was identified significant disease proportion of lymphomas and is prone to relaps-
per 1 placenta in all cases, and in Group-I - 2 mainly. The anastomosing vessels ing after therapy. Lately, new therapeutic approaches beyond con-
average diameter in the FGR-group (4.4 mm) exceeded that in Group-II by 2.6 ventional chemotherapy have emerged focusing on the interplay
times (1.7 mm). The average value of the order of the anastomosing vessels between lymphoma cells and the surrounding reactive cells of the
branching in Group-II was 4, and in the FGR-group - 2.6. microenvironment.
Conclusion: In FGR-group, the highest percentage was for arteriovenous Methods: Here we report the immunophenotypic investigation of the
anastomoses - 57% of all cases, and veno-venous and arteriovenous anas- microenvironment of a clinically well characterised cohort (study
tomoses - on 43% of each. Only arterio-arterial anastomoses were detect- SAKK35/10) including 135 evaluable treatment naïve FL patients in need
ed in placentas without FGR. of treatment, who have been treated with either rituximab (R) only or a
In FGR, the percentage of anastomoses detection is higher, the anasto- combination of rituximab and the immunomodulatory drug lenalidomide
mosing vessels diameter is greater, and their branching order is less than (R/R). After initial large-scale phenotypic analysis of 34 tissue-
in placentas without FGR.
Virchows Arch

microarrayed biopsies focusing on prognostic impact, several promising - Oncology Center, Department of Pathology and Laboratory Medicine,
markers for T-cell subgroups were selected for further evaluation of the Poland, 3 Maria Sklodowska-Curie Institute - Oncology Center,
whole cohort of 135 patients. Department of Lymphoid Malignancies, Poland, 4 Nalecz Institute of
Results: High ratio of CD4- to CD8-positive T cells (p=0.009) and an Biocybernetics and Biomedical Engineering, Polish Academy of
increased amount of PD1-positive T-cells (p=0.007) were associated with Sciences, Poland, 5 Department of Pathology, The Maria Skłodowska-
inferior progression free survival (PFS) in the whole cohort. Interestingly, Curie Memorial Cancer Center and Institute of Oncology, Warsaw,
the prognostic impact of PD1-positive T-cells and the CD4/CD8 ratio was Poland
lost in the R/R subgroup. In this group, high amounts of GATA3-positive
TH2-equivalents were associated with better PFS (p<0.001) and overall Background & Objectives: Enhancer of Zeste Homolog 2 (EZH2) is a
survival (p=0.030). catalytic subunit of polycomb repressive complex 2 and, EZH2 inhibitors
Conclusion: We identified tumour microenvironmental characteristics are histone-modifying enzymes tested for the personalised treatment of
which may allow prognostic stratification with respect to immuno- and hematological malignancies. EZH2 overexpression correlates with more
combined immuno- and immunomodulatory therapy. Our analysis impli- aggressive clinical behavior and poor overall outcome i.e. in breast, pros-
cates that lenalidomide might help to overcome the adverse prognostic tate and endometrial cancer and, diffuse large B-cell lymphomas. EZH2
implication of higher amounts of regulatory T cells and that it may have mutational status in follicular lymphoma (FL) has been analysed recently
particularly favorable effects in cases with higher amounts of TH2- but the significance of EZH2 protein overexpression is still not fully
equivalents as demonstrated by GATA3-positive T-cells. investigated.
Methods: 68 FL cases were revised according to an update of WHO
2017 diagnostic recommendations. From formalin fixed paraffin embed-
OFP-13-003 ded FL 5 tissue microarrays were constructed (3 cores from different
PDL1 in lymphomas with Hodgkin Reed Sternberg (HRS) morphol- representative areas, 1 mm diameter). Immunohistochemical staining of
ogy: a troubleshooter EZH2 (Ventana, SP129, RTU) was performed. Scoring methods included
E. Leoni1, L.F. Vivian2, F. Magnoli1,3, F. Sessa2, M.G. Tibiletti3, S. semiquantitative assessment and digital image analysis with cut-off point
Uccella2 ≥70% of strong nuclear reaction for expression. Selection of 35 patients
1
University of Insubria, Varese, Italy, 2 Unit of Pathology, Department of that did not receive systemic induction treatment after the initial diagnosis
Medicine and Surgery, University of Insubria, Varese, Italy, 3 Department was done; then the cohort was stratified by the time to the systemic
of Pathology, ASST Sette Laghi, Varese, Italy treatment start: 1) patients for which systemic treatment started within
the first 24 months; 2) those for which systemic treatment started after
Background & Objectives: The immune checkpoint PD-1/PDL1 has 24 months from diagnosis. Statistical differences for both pathological
emerged as a mechanism used by certain malignancies such Hodgkin and clinical continuous and categorical variables were tested using
lymphoma to evade immune control. Genetic abnormalities at 9p24.1 Kruskal-Wallis ranks sum test and Pearson’s chi-squared test with conti-
have been reported with high incidence in classical Hodgkin lymphomas nuity correction, respectively.
(cHL) producing PDL1 overespression. Results: EZH2 was expressed in 22.85% of cases. It was observed in
The aim of this study was to evaluate the PDL1 expression in cHL and in 14.3% vs. 62.5% (p<0.05) cases among groups of patients with systemic
aggressive non-Hodgkin lymphomas morphologically characterised by the treatment after vs. within 24 months respectively. There were no differ-
presence of HRS-like cells (NHL), in order to assess PDL1 diagnostic value. ences in the clinical or other pathological characteristics is in the year of
Methods: Immunoreactivity for PDL1 and PD-1 was evaluated in a diagnosis between two groups.
cohort of 13 HL and 16 NHL diagnosed between 2014 and 2018. Conclusion: EZH2 protein expression was more frequently observed in
Fluorescence in situ hybridization (FISH) on paraffin embedded speci- the group that required the introduction of systemic therapy within the
mens was performed to detect CD274 (a.k.a PDL1),PDCD1LG2 (a.k.a first 24 months. EZH2 should be evaluated more comprehensively both
PDL2) gene cluster amplifications, usig Zyto Light SPEC with EZH2 mutational status to determine a sensitive biomarker for a first
CD274,PDCD1LG2/CEN 9 Dual Color Probe provided by ZytoVision line selection of patients for targeted EZH2 inhibitor therapies.
(Bremerhave, Germany).
Results: All HL showed 2+ to 3+ PDL1 immunohistochemical expres-
sion. Among NHL, PDL1 expression was detected in only 4 (25%) cases: OFP-13-005
3/3 anaplastic large cell lymphoma (ALCL) and 1/11 diffuse large B cell Gene cluster amplifications of PDL1/2 in aggressive primary
lymphoma. PD-1 expression was identified in a low percentage of T extranodal DLBCL
lymphocytes in all NHL and in most cHL, whereas the 2 nodular lym- S. Weissinger1, M. Disch2, M. Zahn1, R. Marienfeld1, P. Moeller1, A.
phocyte predominant HL showed PD-1 expression in >50% of T cells. Viardot3, J. Bloehdorn3
1
FISH analysis showed 9p polisomy in more than half cases without cor- University Hospital Ulm, Institute of Pathology, Germany, 2 University
relation with PDL1 immunohistochemistry whereas amplification of the Ulm, Institute of Pathology, Germany, 3 University Hospital Ulm,
target region was not observed. Department of Internal Medicine III, Germany
Conclusion: Our study suggests that PDL1 espression is characteristic of
cHL and ALCL, and represent a valid tool in differentiating HL from Background & Objectives: Cancer cells are capable to evade the im-
some NHL with HRS-like cells, especially T cell histiocyte rich large B mune system through altered checkpoints. A considerable heterogeneity
cell lymphoma. regarding responses to checkpoint blockade have been observed in lym-
phomas. The scope of this study was therefore to investigate gene cluster
amplifications of the PDL1/2 locus in a large cohort of primary extranodal
OFP-13-004 DLBCL.
Enhancer Zeste Homolog 2 (EZH2) expression is associated with a Methods: Amplifications of the PDL1/2 locus on chromosome 9p24.1
shorter time to the first systemic therapy in follicular lymphoma were investigated by FISH in n=89 DLBCL (GCB n=22, nonGCB n=42),
A. Szumera-Cieckiewicz1, K. Sokol1,2, G. Rymkiewicz2, E. Paszkiewicz- with primary involvement of ear nose throat (ENT), central nervous sys-
Kozik3, J. Poleszczuk4, A. Borysiuk2, M. Kotarska3, J. Walewski3, M. tem, mediastinum (PMBCL), gastrointestinal, skin (comprising classic
Prochorec-Sobieszek5 leg-type (LT) and other cutaneous DLBCL) and other sites. Each case
1
Institute of Haematology and Transfusion Medicine, Diagnostic was screened on single cell level for frequency of gains (relative copy
Haematology Department, Poland, 2 Maria Sklodowska-Curie Institute gain + amplification), losses and polysomy.
 Virchows Arch

Results: The average of the different aberrations (in % of counted OFP-13-007

tumour cells) did not show significant differences either in terms Clinical routine assessment of tumour mutational burden in non-
of subtype (nonGCB/GCB) nor with regard to location. Most small cell lung cancer and melanoma using three different targeted
aberrations were found in ENT (copy gain: 21%, copy loss: sequencing panels - a single center experience from the Laboratory of
17%) and in gastrointestinal DLBCL (polysomy: 21%). Clinical and Experimental Pathology (Nice, France)
Concerning cutaneous and LT DLBCL, the most frequently aber- S. Heeke1, J. Benzaquen2, E. Long-Mira3, B. Audelan4,5, V. Lespinet6, O.
ration was polysomy in 18% of the tumour cells in cutaneous Bordone6, S. Lalvèe6, K. Zahaf6, M. Poudenx2, P. Dugourd7, M.
DLBCL, whereas in LT only 9% of those cells were found. Chassang 7 , T. Passeron 7,8,5 , H. Delingette 4,5 , C. Marquette2 , V.
Conclusion: Collected data suggests that there is no significant Hofman3,9, M. Iliè3, P. Hofman3,9
1
difference in gene cluster amplification of PDL1/2 or polysomy in Team 4 IRCAN, Inserm U1081/CNRS 7284, IRCAN, Nice, France,
2
investigated extranodal DLBCL, both with regard to the nonGCB/ Universitè Côte d'Azur, CHU de Nice, University Hospital Federation
GCB subtype and location of primary involvement. Most aberra- OncoAge, Department of Pulmonary Medicine and Oncology, France,
3
tions were found in ENT (copy gain) and gastrointestinal DLBCL Universitè Côte d'Azur, CHU de Nice, University Hospital Federation
(polysomy). OncoAge, Laboratory of Clinical and Experimental Pathology, France,
4
Epione Team, Inria, Sophia-Antipolis, France, 5 University Côte d'Azur,
Stephanie Weissinger and Andreas Viardot receive research funding from Nice, France, 6 Laboratory of Clinical and Experimental Pathology,
Bristol-Myers Sqibb. Biobank BB-0033-00025, CHU of Nice, France, 7 Department of
Dermatology, CHU of Nice, France, 8 INSERM U1065, C3M, Nice,
France, 9 Universitè Côte d'Azur, CHU de Nice, University Hospital
OFP-13-006 Federation OncoAge, Hospital-Integrated Biobank (BB-0033-00025),
Characterisation of atypical dMMR (deficient MisMatch Repair) France
tumours: a study from a large cohort of 4948 cases
J. Selves1, M. Jaffrelot1, A.P. Laurenty2, N. Fares3, S. Icher1, A.C. Background & Objectives: Tumour mutational burden (TMB) has
Brunac1, M. Danjoux1, J. Meilleroux1, C. Toulas4, E. Chipoulet5, A. been proposed as a promising biomarker for the stratification of
Staub6, R. Guimbaud3 patients for anti-cancer immunotherapy. However, TMB is yet to
1
CHU-IUCT-ONCOPOLE, France, 2 Clinique Croix du Sud Toulouse, be standardised. Various pre-analytical factors must be carefully
France, 3 CHU-Toulouse, France, 4 Institut Claudius Regaud IUCT- controlled before a daily use of TMB is possible. The aim of this
ONCOPOLE, France, 5 Institut Claudius Regaud -IUCT-ONCOPOLE, study was to analyse how the Oncomine TML and the Qiagen
France, 6 CH Montauban, France QIAseq TMB panels can be implemented in a clinical molecular
pathology lab and if the clinical prediction could be compared to
Background & Objectives: MMR testing is now currently performed in the FoundationOne assay.
several tumours, using two methods: MMR proteins immunohistochem- Methods: Sixty non-small cell lung cancer and thirty-six melanoma pa-
istry (IHC) and molecular biology (MB) for assessing microsatellite in- tients with first- or second-line treatment with immune checkpoint inhib-
stability (MSI). Classically, dMMR tumour corresponds to loss of expres- itors were included in this study. Formalin-fixed paraffin-embedded
sion of MLH1 and PMS2 or MSH2 and MSH6, associated with MSI. The (FFPE) tissue sections were either analysed in-house using the
aims of our study was to describe the frequency and the characteristics of Oncomine TML (Thermo Fisher, Waltham, USA) and the Qiagen
atypical dMMR profiles. QIAseq TMB panels (Qiagen, Hilden, Germany) or sent out to external
Methods: All MMR testing performed in our MB platform between 2007 testing with FoundationOne assay (Foundation Medicine, Cambridge,
and 2017 (n=4948) were checked to select cases with both available IHC USA). Durable clinical benefit (DCB), defined by at least 6 months with-
and MB (n=3800). The 585 dMMR cases were reviewed and atypical out disease progression was evaluated.
cases were defined by: microsatellite stability (MSS) with loss of expres- Results: TMB is well correlated between the panels (R² > 0.7) but
sion of a pair of proteins; MSI-H with loss of expression of non-paired correlation decreases in samples with lower tumour-cell content.
proteins or with expression of the four proteins; MSI-low. Biological data Deamination of FFPE samples had a strong impact on the sequencing
of atypical cases were controlled if necessary and clinical data were col- accuracy using the Oncomine TML and the QIAseq TMB panels and
lected for each case. required enzymatic repair using Uracil-DNA glycosylase (UDG)
Results: We identified 97 atypical cases and after controls, 19 cases (21 highlighting specific sample requirements for precise TMB assess-
%) were re-classified allowing to finally identify 89 atypical cases. ment. All panels were equally well correlated with DCB value in
Conclusion: We showed that 15% of dMMR tumours have an atypical NSCLC but not in melanoma. Updated data will be present during
profile. They mainly involve non-colorectal cancer with a strong predic- the congress.
tion for genetic syndromes. Their therapeutic impact must now be eval- Conclusion: High TMB has been associated with DCB in NSCLC but
uated. not in melanoma patients. The Oncomine and QIAseq panels allow the
“in-house” assessment of TMB with good correlation to the
FoundationOne assay. However, further standardization for the TMB
IHC PMS2 or MSH6 MLH1/PMS2/MSH6/ MSH2/MSH6 or Aberrant loss of
assessment in different centers and external quality controls are urgently
MB isolated loss 53 MSH2 normal MLH1/PMS2 proteins 15
needed for using the commercially available TMB panels in daily prac-
expression 5 loss 16
tice.

MSI-high 43 3 13
OFP-13-008
MSI-low 1 2 8 0
Novel role of NMI (N-myc interactor) in chemotherapy response
MSS 9 8 2 through a mitochondrial dysfunction mediated mechanism and as a
Clinical Genetic syndromes Genetic syndromes Non-Colorectal Complex potential target for breast cancer therapy
characteristics (73%) cancer (63%) inactivation K. Lee1, E.H. Hwang1, S.E. Kang1, H.S. Ryu2
1
of MMR Biomedical Research Institute, Seoul National University Hospital,
proteins Republic of Korea, 2 Department of Pathology, Seoul National
University Hospital, Republic of Korea
Virchows Arch

Background & Objectives: Mitochondria have a central role in the PBAC precursor lesions, show a favorable prognosis despite the frequent
cancer cell phenotypes of altered redox homeostasis, metabolic rewiring. occurrence of associated invasive PBAC at the time of diagnosis. ITPN
Disruption of redox homeostasis is a crucial factor in the development of molecular carcinogenesis as well as its relation to the cancer genes driving
chemoresistance, which is a major obstacle to successful treatment with PBAC carcinogenesis are poorly understood. The aim of the present
cancer patients. Recently, the involvement of NMI in drug resistance was study was to analyse the mutational profile of ITPN using whole exome
sporadically reported but the mechanisms of NMI are still far from elu- sequencing (WES) in order to identify driver genes and potential
cidation. In this study, we investigated NMI as a potential target of cancer therapeutical targets.
therapy and investigated its contribution in breast cancer metabolism. Methods: In this study the genetic landscape of 17 ITPN of the
Methods: Clinical impact was assessed by IHC staining of NMI in FFPE pancreato-biliary system (11 biliary and 6 pancreatic cases) was exam-
tissue from 153 breast cancer patients who received adjuvant chemother- ined. Tumour tissue and matching normal tissue were whole-exome se-
apy. The biological function of NMI was studied in vitro and in vivo, quenced to determine single nucleotide variants (SNV), Indels and copy-
Using NMI inhibition (si/shRNA) or overexpressing cell lines, 3D cul- number variants (CNV).
tures were performed on various ECM (matrigel, matrigel:collagen mix), Results: The identified somatic mutations predominantly involved few
cell titer-glo assays were performed for anticancer drug susceptibility. core signalling pathways despite high genetic heterogeneity with diverse
In vivo tumour formation capacity was assessed in NSG mice. mutational spectra: chromatin remodelling (e.g. ARID1A/1B/2), Wnt-
Mitochondrial membrane potential and ROS were analysed by FACS pathway (e.g. recurrent BCL9 mutations), MAPK signalling and TGF-ß
using mitotracker (Red, Green), mitoSOX and DCFDA. Seahore analyser signalling (e.g. FGFR2). No somatic SNV were found in classical cancer
was utilized to assess the OXPHOS and glycolysis in breast cancer cells. genes KRAS, CDKN2A and GNAS, TP53 and SMAD4 were affected in a
Results: We observed NMI1 expression were higher in non-complete minority of cases (6 %, respectively).
response (nCR, n=78) compared to complete response (CR, n=78) by Identified chromosomal variations primarily affected four major path-
analysis of total 156 patients with locally advanced breast cancer who ways: chromatin remodelling, cell cycle, Wnt-signalling and mTOR-sig-
received neoadjuvant chemotherapy (IHC score 1.275 vs. 0.855, respec- nalling. Recurrent chromosomal deletions were predominantly identified
tively; p=0.012). Biologically, si/shRNA-mediated knockdown of NMI on chromosome 1p36, 3p14-22 (restricted to biliary ITPN), 6q21-22 and
expression in various breast cancer cells significantly suppressed cell 14q21-22, whereas chromosomal gains were found on chromosome 1q,
proliferation in 3D culture systems, increased apoptosis and sensitivity 8q and 20q.
to chemotherapeutic agents. Furthermore, silencing NMI expression Conclusion: Our study reveals for the first time the genetic landscape of
inhibited xenograft tumour growth and lung and liver metastasis in biliary ITPN and highlight that the genetic profile of ITPN of the
NSG mice. Mechanically, silencing NMI expression increased high levels pancreato-biliary system profoundly differs from PBAC molecular carci-
of hydrogen peroxide (H2O2) production, but not superoxide (O2-), sub- nogenesis. ITPN largely lack alterations of the PBAC driver genes.
sequently reduced mitochondrial respiratory capacities in MDA-MB-231 Instead the genetic changes of ITPN focus on key signalling pathways
and BT-20 breast cancer cells. Ablation of NMI also inhibited mitochon- (in particular chromatin remodelling and Wnt-pathway), recurrent chro-
drial biogenesis in both cells as assessed by the number of mitochondria mosomal aberrations as well as recurrent alterations of druggable targets
measured by transmission electron microscopy (TEM). Consistent with (e.g. BCL9).
this result, mitochondrial membrane potentials (mtMPs) were also down-
regulated. Conversely, induction of NMI downregulated hydrogen per- This work was supported by German Research Foundation.
oxide and increased basal and maximal mitochondrial respiratory
capacities.
Conclusion: Collectively, these results imply that NMI potentiates OFP-13-010
oxidative phosphorylation (OXPHOS) and protected cells to che- Methylation patterns in dysplasia in inflammatory bowel disease
motherapeutic reagent from hydrogen peroxide-induced oxidative patients
deaths through its role in mitochondrial biogenesis. Therefore, S. Mata1, I. Rosa2, P. Silva3, F. Magro4, F. Carneiro5, A. Peixoto4, M.
targeting NMI can be potential treatment for drug resistance in Silva4, H.T. Sousa6, J. Roseira6, J. Parra7, R. Barosa8, A. Vieira8, M.J.
breast cancer cells. Brito9, P. Lago10, A. Coelho11, J. Moleiro2, J. Pereira da Silva2, R.
Fonseca12, C. Albuquerque3, A. Dias Pereira13
1
The study was supported by the National Research Foundation of Korea Patholology Department, Instituto Português de Oncologia de Lisboa,
(2016R1C1B2013275 and 2019R1C1C1006465). Francisco Gentil, EPE, Portugal, 2 Gastroenterology Department,
Instituto Português de Oncologia de Lisboa, Francisco Gentil, EPE,
Portugal, 3 Molecular Pathobiology Investigation Unit, Instituto
OFP-13-009 Português de Oncologia de Lisboa, Francisco Gentil, EPE, Portugal,
4
Whole exome sequencing of pancreatic and biliary intraductal Gastroenterology Department, Centro Hospitalar de São João, EPE,
tubulo-papillary neoplasms reveals a distinct genetic landscape Portugal, 5 I3S/Ipatimup; Centro Hospitalar de São João; FMUP,
C. Groß1, T. Engleitner2, J. Weber2, M. Jesinghaus3, B. Konukiewitz1, A. Portugal, 6 Gastroenterology Department, Centro Hospitalar do
Muckenhuber1, K. Steiger1, W. Weichert4, V. Adsay5, G. Kloeppel1, I. Algarve, EPE, Portugal, 7 Pathology Department, Centro Hospitalar do
Esposito6, R. Rad2, A.M. Schlitter1 Algarve, EPE, Portugal, 8 Gastroenterology Department, Hospital Garcia
1
Institute of Pathology, TUM School of Medicine, Technical University de Orta, EPE, Portugal, 9 Pathology Department, Hospital Garcia de Orta,
of Munich, Germany, 2 Institute of Molecular Oncology and Functional EPE, Portugal, 10 Gastroenterology Department, Centro Hospitalar do
Genomics, TUM School of Medicine, Technical University of Munich, Porto, EPE, Portugal, 11 Anatomical Pathology Service, Department of
Germany, 3 Institute of Pathology, Technical University of Munich, Pathology, Hospital and University Center of Porto, Porto, Portugal,
Germany, 4 Technical University of Munich, School of Medicine, 12
Pathology Department, Instituto Português de Oncologia de Lisboa
Institute of Pathology, Germany, 5 Koc University, School of Medicine, Francisco Gentil E.P.E., Lisbon, Portugal, 13 Gastroenterology
Department of Pathology, Turkey, 6 Institute of Pathology, Heinrich Department, Instituto Português de Oncologia de Lisboa Francisco
Heine University and University Hospital, Düsseldorf, Germany Gentil E.P.E., Lisbon, Portugal

Background & Objectives: Pancreato-biliary adenocarcinomas (PBAC) Background & Objectives: Inflammatory Bowel Disease (IBD) with
are highly aggressive neoplasms with poor prognosis. In contrast, colonic involvement increases colorectal cancer risk. Guidelines recom-
intraductal tubulo-papillary neoplasms (ITPN), recently described rare mend surveillance strategies based on the early detection of dysplasia.
 Virchows Arch

The distinction between IBD-related and sporadic dysplasia in IBD pa- PhD Grant by FCT (grant number SFRH/BD/132751/2017). Project
tients is difficult. IBD-related carcinogenesis has distinctive features and Grant by FCT (grant number POCI-01-0145-FEDER-29043).
some data favors the importance of abnormal DNA methylation in this
carcinogenesis.
This study aims to define methylation patterns in patients with a colonic OFP-13-012
cancer or dysplasia diagnosis following an IBD diagnosis. Detection of EGFR mutations in ctDNA in plasma samples of
Methods: In this national multicentric cross-sectional study, 91 samples NSCLC patients by two simultaneously applied methods
of colonic mucosa, with and without dysplasia, from 35 patients with IBD A. Farkasova1, K. Scheerova1, L. Plank2,1
1
(ulcerative colitis in 29) were studied (9 patients with IBD-related MBC Ltd., Slovakia, 2 Department of Pathology, Comenius University
dysplasia/cancer and 26 patients with sporadic dysplasia/cancer). The Jessenius Medical Faculty and University Hospital, Slovakia
Cpg islands methylation patterns of 67 genes’ promoter regions were
analysed by Methylation-specific Multiplex Ligation-dependent Probe Background & Objectives: The circulating tumour DNA (ctDNA)
Amplification, using commercial kits (ME001, ME002, ME004, analysis might contribute to the identification of specific genes
ME011, ME042) and Coffalyser.NET (MRC-Holland®) software. mutational status of cancer patients. It can be used both at the
Results: Of the 35 patients, 25 had at least 1 endoscopically described as baseline cancer primodiagnostics as well as for monitoring the
adenoma-like lesion, 4 had at least 1 non-adenoma-like lesion, 3 had treatment response. For patients with non-small cell lung cancer
cancer and 3 had dysplasia in flat mucosa. No patient had both (NSCLC), it seems to be possible to use this analysis in particular
adenoma-like and non-adenoma-like lesions. Methylation of IGF2, to identify EGFR mutations that significantly affect the selection of
RARB, ESR1, CHFR, CDH13, WT1, GATA5, WIF1 genes’ promoters an appropriate targeted therapy at baseline or during the treatment´s
was significantly associated to dysplasia/cancer; methylation of MSH6, follow-up.
TIMP3 was significantly associated to IBD related dysplasia/cancer. Methods: In the period Sept. 2018 – March 2019 we analysed ctDNA
MSH6, MSH3, RUNX3, CRABP1, TP73, RARB, CDH13, PAX5, WT1, isolated from the separated plasma of NSCLC patients either when a/
THBS1, TP53, SFRP1, WIF1, APAF1, BCL2 promoters’ methylation the biopsy or cytology material was not suitable for EGFR gene
were significantly associated to active IBD. MSH6’s methylation mutation analysis or b/ when a relapse occurred during TKI anti-
remained significantly associated to IBD related dysplasia/cancer in mul- EGFR treatment following the primary analysis of tissue specimens.
tivariate analysis (p=0,029). All the samples were examined by two simultaneously applied
Conclusion: Methylation analysis, namely of MSH6, may contribute to methods. The first analysis used ctDNA isolated with the cobas®
the classification of dysplastic lesions in IBD patients – to be further cfDNA Sample Preparation Kit and was performed on cobas®
tested in a prospective study. Z480 platform (Roche Molecular Diagnostics) with the cobas®
EGFR Mutation Test v2 CE-IVD kit. The second one used ctDNA
isolated with QIAamp circulating nucleic acid kit (Qiagen) and the
OFP-13-011 tests were performed on Cube 6i flow cytometer (Sysmex Inostics)
XIST promoter methylation status as putative molecular biomarker using OncoBEAMTM EGFR Kit v2 (RUO).
for testicular germ cell tumours Results: a/ in the primodiagnostic samples (n = 25) both the
J. Lobo1, S.P. Nunes1, D. Barros-Silva1, V. Miranda-Gonçalves1, A. van methods allowed to identify the same numbers and types of muta-
den Berg2, A. JM Gillis2, L. HJ Looijenga3, C. Jerónimo1, R. Henrique1 tions: exon 19 del mutation was detected in 4 (16 %) and L858R
1
IPO Porto, Portugal, 2 PMC Utrecht, The Netherlands, 3 PMC Utrecht & mutation in 3 patients (12 %), while a simultaneous exon 19 del
Erasmus MC Rotterdam, The Netherlands and T790M mutation was identified in one patient (4 %); b/ in a
setting of patients with relapse of disease during the anti-EGFR
Background & Objectives: Testicular germ cell tumours (TGCTs) TKI treatment (n = 13), both the methods showed identical results
are developmental cancers, and this model has been the main driver in 11/13 (85 %) cases (5 without any mutation, 2 with exon 19 del,
in uncovering novel clinically relevant biomarkers. The process of 2 with simultaneous exon 19 del and T790M mutation and 1 with
X-chromosome inactivation by XIST expression due to promoter exon 21 /L858R/ mutation). In remaining 2 cases (15 % of all) the
demethylation is observed in these tumours, based on their Cobas method allowed to identify exon 19 del mutation only, while
supernumerical X-chromosome constitution. Here we analyse the the examination with BEAMing method discovered a combination
promoter methylation status of XIST in a series of TGCT tissues of exon 19 del together with T790M mutation.
and derived cell lines.
Conclusion: This pilot study allows to conclude that ctDNA analyses
Methods: A total of 250 FFPE TGCT samples, 4 (T)GCT cell lines and
could be used to assess the EGFR gene mutation status in situations, when
54 testicular parenchyma samples were investigated for the methylation
the patient´s biopsy and/or cytology material is not quantitative sufficient
status of the XIST promoter region IV using bisulfite treatment and quan-
and/or qualitatively suitable for the DNA tests. These methods might be
titative methylation-specific PCR (qMSP) analyses. Diagnostic perfor-
applied also for the monitoring of the therapeutic response and early
mance was assessed with ROC curve analysis.
detection of relapse due to the emergence of resistant mutations.
Results: Seminomas showed significantly lower content of methylated
However, the necessity of an implementation of more sensitive methods
XIST fragments compared to Non-Seminomas or normal
into the routine practice should be verified in large series of cases.
testis(p<0.0001) (Seminoma vs. normal testis and vs. Non-Seminoma:
AUC 0.81 and 0.83, respectively). Seminomas contained significantly
This work was supported by a donation grant from Boehringer Ingelheim
higher content of demethylated XIST compared to Non-
GmbH no. 213346 and AstraZeneca.
Seminomas(p<0.001), similarly in the “Seminoma-like” cell line
TCam2 compared to the Non-Seminoma cell lines NCCIT, 2102Ep and
NTera2(p<0.0001). A strong positive correlation between Johnsen score Tuesday, 10 September 2019, 17:15 - 19:15, Galliéni 4
(JS) and XIST demethylation was identified (r=0.75, p<0.0001). Only OFP-14 | Gynaecological Pathology
1/54 testis with JS<4(premeiotic cells only) showed presence of XIST
demethylation.
Conclusion: Differential methylation status of XIST promoter occurs OFP-14-001
among TGCT subtypes and in testicular parenchyma with different Microsatellite instability and its relation to myoinvasive pattern in
Johnsen score. Further analysis in liquid biopsies is warranted. low stage/low grade endometrioid endometrial carcinoma
Virchows Arch

I. Ruz-Caracuel1, A. Berjón2, J.L. Ramón-Patiño3, L. Yèbenes2, î López- signal size, percentage of nuclei with coarse signal, pattern of nuclear
Janeiro2, A. Hernández4, M. Mendiola2, A. Redondo3, A. Peláez-García2, signal, cytoplasmic signal amount and presence of “reservoir-like cells”.
D. Hardisson2 Signals were either fine (small, stippled) or coarse (dense, prominent).
1
Hospital Universitario La Paz, Spain, 2 Pathology, Hospital Results: 174 cores had interpretable p16 and HPV-ISH results. 138 cases
Universitario La Paz, IdiPAZ, Madrid, Spain, 3 Oncology, Hospital (79.3%) showed concordant p16/HPV status, including 32 cases of p16-/
Universitario La Paz, IdiPAZ, Madrid, Spain, 4 Gynaecology, Hospital HPV- (G1, 23.2%) and 106 cases of p16+/HPV+ (G2, 76.8%). 36 cases
Universitario La Paz, IdiPAZ, Madrid, Spain (20.7%) showed discordant p16 and HPV results including 8 cases of
p16+/HPV- (G3, 22.2%) and 28 cases of p16-/HPV+ (G4,77.8%). Ki-
Background & Objectives: Endometrial carcinoma is the most prevalent 67 average in the p16+/HPV+ G2 (56%) was significantly higher than in
gynaecologic malignant neoplasm worldwide. Most of these cancers are the p16- groups G1/HPV- (41%) or G4/HPV+ (44%), (p-value 0.002 and
low grade (grade 1-2), low FIGO stage (I or II) endometrioid carcinomas. In 0.01, respectively).
this group, microsatellite instability (MSI) has been considered as a marker Conclusion: Proliferation rate was statistically higher in p16+/HPV+
of poor prognosis. Our objective is to study if there is a relation between cases than p16- cases regardless of HPV status. Ki-67 and viral load, were
microsatellite instability and any of the myoinvasive patterns described. higher in HPV+ cases with diffuse strong p16 compared to variable/weak
Methods: Endometrial cancers submitted for surgery in a single tertiary p16. The cases with reservoir-like cells showed a higher proliferation rate
hospital between 2003 and 2015 (n=512) were selected for this study. than cases without. There was no discernible correlation between HPV
Inclusion criteria were: (i) endometrioid endometrial carcinomas, (ii) staining pattern and p16 positivity.
grade 1 or 2 with (iii) FIGO stage I or II. Slides were reviewed to annotate
the myoinvasive pattern present in each case according to the classifica-
tion described by Cole & Quick, 2013; as well as the presence of mucin- OFP-14-003
ous and/or squamous differentiation. MSI was studied by Programmed death-ligand 1 (PD-L1) in cervical invasive squamous
immunoexpression of mismatch repair proteins (MLH1, PMS2, MSH2, cell carcinoma and squamous intra-epithelial lesions in HIV infected
and MSH6). Those cases with follow-up and evaluable immunohisto- women: comparison with non-infected patients
chemistry were considered for analysis (n=201). A chi-squared or M. Brito1, P. Sequeira1, A. Quintas1, I. Silva1, C. Martins2, A. Fèlix3
1
Fisher´s exact test was used to evaluate correlations. Hospital Garcia de Orta, Almada, Portugal, 2 Nova Medical School,
Results: Our series has the following distribution according to the main Universidade Nova, Lisbon, Portugal, 3 Instituto Portugues de
myoinvasive pattern: infiltrative glands (49.8%), broad front (10%), Oncologia de Lisboa, Nova Medical School - UNL, Portugal
adenomyosis-like (9.5%), microcystic, elongated and fragmented glands
(MELF) (9%), adenoma malignum (0.5%), and non-infiltrative (21.4%). Background & Objectives: Programmed death-ligand 1 (PD-L1) pro-
MSI was positively correlated with relapse (p=0.007), infiltrative glands tein is overexpressed in HPV infected carcinoma cells and inhibits T
myoinvasive pattern (p=0.032), histological grade 2 (p=0.005), lymphocyte cytotoxic activity. The status of PD-L1 is not well established
lymphovascular invasion (p=0.003), and mucinous differentiation in malignant neoplastic cells of HIV infected patients. The fact that PD-
(p=0.02). L1 membrane expression in tumour cells has been correlated with re-
Conclusion: In our series, MSI is an adverse factor correlated with re- sponses to anti-PD-L1 immunotherapy, makes this knowledge
lapse. The myoinvasive pattern associated with MSI is the presence of mandatory.
infiltrative glands. Our aim was to study PD-L1 expression in cervical neoplastic epithelial
cells of HIV infected women in comparison with non-HIV infected
This project is funded by a FIS2017 grant (PI17/01723). patients.
Methods: We analysed 110 cervical samples: 53 HIV+ patients (12 squa-
mous cell carcinomas (SCC), 7 High-Grade Intra-epithelial Squamous
OFP-14-002 Lesions (HSIL) adjacent(adj) to SCC, 21 HSIL, 20 Low-Grade Intra-epithe-
Detailed description of high-risk HPV in situ hybridisation patterns lial Squamous Lesions (LSIL)); 57 from HIV- patients (17 SCC, 17
in endocervical adenocarcinoma and correlation with p16 adjHSIL, 20 HSIL, 20 LSIL). PD-L1 immunohistochemical-evaluation used
immunohistochemistry SP263Ab (Roche). The neoplastic cells percentage of membrane staining
M. Shahi1, L. Hoang2, T. Kiyokawa3, S. Stolnicu4, R. Soslow5, K. Park6 was scored as: 0 (<1%); 1(≥1% to 5%); 2 ( ≥5-10%); 3 (≥10-20%); 4 (≥20-
1
University of Chicago, USA, 2 University of British Columbia, Canada, 50%); 5 ( ≥50%). Data were analysed by Fisher's exact test.
3
Department of Pathology, the Jikei University School of Medicine, Results: In HIV infected women, 8/9 invasive SCC (89.9%) were posi-
Japan, 4 Department of Pathology, University of Medicine, Pharmacy, tive (22.2% score 5) and 8/10 invasive SCC (80%) in HIV non-infected
Sciences and Technology of Targu Mures, Romania, 5 Memorial Sloan women (10% score5). HSIL adjacent to carcinoma were positive in all 7
Kettering Cancer Center, USA, 6 Department of Pathology, Memorial cases from HIV+ patients and negative in all non-HIV patients (n=17)
Sloane Kettering Cancer Center, New York, USA (p<0,0001). As for HSIL, non-adjacent to invasive carcinoma, 4/21 cases
(19%) were positive in the HIV+ group and none in the HIV- group. No
Background & Objectives: Cervical adenocarcinoma are Human positive cases were found in LSIL and normal epithelium in both groups.
Papilloma Virus (HPV) and non-HPVassociated. p16 immunohistochem- Conclusion: 1. PD-L1 is highly expressed in SCC both in HIV- and
ical (IHC) staining is used as a surrogate marker for HPV infection. High- HIV+ women.
risk HPV ribonucleic acid in situ hybridization (HR HPV RNA-ISH) is 2. HSIL, in HIV infected women, are more often positive for PD-L1, than
more sensitive and specific than p16 to detect HPV. There have been no in HIVnon-infected women, and this difference is statistically significant
descriptions of staining pattern of HPV RNA ISH in HPV associated (p<0,0001) in HSIL adjacent to SCC. This expression may contribute to a
adenocarcinomas. Herein, we describe various staining patterns in glan- higher progression of these lesions to carcinoma, in HIV infected women.
dular epithelium infected by HPV and correlate with p16 and Ki-67 IHC
expression.
Methods: IHC for p16 and Ki-67, and HR HPV RNA-ISH were per- OFP-14-004
formed on two tissue microarray (TMA) slides composed of 200 cases of Supporting the hypothesis of a dualistic model for high-grade serous
invasive endocervical adenocarcinoma. p16 was scored as positive (dif- carcinoma: a genetic and pathological study
fuse strong/diffuse weak/patchy strong), or negative if absent. Ki-67 was A. De Leo1, G. Santandrea2, C. Ceccarelli3, G. Barbero4, S. Ferrari4, D.
scored semi-quantitatively. HPV ISH was scored for viral load, nuclear Turchetti4, D. Rubino5, A.M. Perrone6, P. De Iaco6, D. Santini7
 Virchows Arch

1
Pathology Unit, Department of Experimental, Diagnostic and Specialty Methods: ECA cases from 7 international institutions were reviewed by a
Medicine, University of Bologna, S. Orsola-Malpighi Hospital, Italy, panel of pathologists for consensus histotype based on recently developed
2
Pathology Unit, S.Orsola-Malpighi Hospital, University of Bologna, International Endocervical Criteria and Classification (IECC). Tissue mi-
Italy, 3 Department of Experimental, Diagnostic and Specialty croarrays were constructed for 179 cases to analyse TFF2 and HIK1083
Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Italy, expression using immunohistochemistry. Both markers were similarly
4
Medical Genetics Unit, S.Orsola-Malpighi Hospital, University of scored and any staining in >5% of tumour cells was considered as
Bologna, Italy, 5 Oncology Unit, S.Orsola-Malpighi Hospital, positive.
University of Bologna, Italy, 6 Gynaecologic Oncology Unit, S.Orsola- Results: Of 179 ECA cases, 126 were of usual-type, 24 GAS, 7 clear cell
Malpighi Hospital, University of Bologna, Italy, 7 Pathology Unit, S. and 22 other types. Of 24 GAS cases, 7 (29%) were positive for TFF2 and
Orsola-Malpighi Hospital, University of Bologna, Italy 10 (42%) for HIK1083, including 5 showing positivity for both markers.
Of 155 non-GAS cases, only 4 (2.6%) showed positivity for TFF2, and 2
Background & Objectives: High-grade serous carcinomas (HGSC) with (1.3%) for HIK1083, none of clear cell type.
BRCA deficiency have recently been described to exhibit characteristic Conclusion: Our results suggest that TFF2 is a promising surrogate
pathological features such as solid, pseudoendometrioid, transitional cell- marker to separate GAS from other types of ECA in association with
like morphology (SET variant), and a particular pattern of invasion in HIK1083. However, since only 1/3 of GAS were positive for TFF2 in
metastatic sites. The aim of the study was to investigate the correlation this series, caution must be paid that negative TFF2 does not exclude a
between BRCA mutational status, age, tumour morphology, serous tubal diagnosis of GAS.
intraepithelial carcinoma (STIC), tumour-infiltrating lymphocytes (TILs)
and peritoneal invasion patterns.
Methods: 75 cases of HGSC were analysed. Pathological features were OFP-14-006
evaluated and classified as previously described. BRCA1/2 analysis Progenitor cells in ovario-fimbrial zone of female uterine adnexa: a
was performed on DNA extracted from formalin-fixed paraffin-embed- potential clue for epithelial tumours pathogenesis
ded (FFPE) tumour tissue through Next Generation Sequencing A. Asaturova1
1
technology. FSBI 'National Center for Obstetrics, Gynaecology and Perinatology
Results: BRCA1/2 mutations were found in 40.7% of cases (79.2% named after V.I.Kulakov' Ministry of Healthcare Russian Federation,
germline mutations and 20.8% somatic mutations). Morphologically, 52.5% Russia
of cases were classified as classic HGSC and 47.5% as SET variant. BRCA-
associated HGSCs were statistically correlated with SET morphology Background & Objectives: Ovarian cancer remains the most deadly
(p=0.0005) and pushing pattern metastases, but not with age, STIC and gynaecological malignant disease in developed countries. Basically, poor
TILs. Compared with classic HGSC, SET tumours were strongly associated prognosis of this disease can be explained by the ineffectiveness of
with pushing pattern of invasion (p=0.0001) and high density of TILs screening programs due to the lack knowledge of the ovarian cancer
(p=0.0001) with number of CD8+ lymphocytes >100/10HPFs (p=0.001). pathogenesis. Since pluripotent cells play a key role in the development
STIC was found in 62.7% of cases and was more frequent in classic HGSC. of neoplastic epithelial changes, verification of the of their localization in
Conclusion: SET-HGSC showed a statistically significant association transition zones (TZs) will help to determine the possibility of simulta-
with BRCA mutation, TILs with high number of CD8+ lymphocytes, neous existence of several potential sources for ovarian carcinoma
and a pushing pattern of peritoneal invasion. These pathologic differences development.
among the classic HGSC and the SET variant, together with their differ- Methods: We investigated 165 tissue samples of the ovary and fallopian
ent relations to BRCA mutations, allow to identify two possible separable tube from patients with benign extraovarian pathology (uterine fibroids
entities, thus supporting the hypothesis of a dualistic model of HGSC. and adenomiosis) and 25 samples with high-grade serous ovarian carci-
noma (HGSC) [(55 fimbriae, 25 parafimbrial zones (PFZ), 25
paraovarian zones (POZ), 35 samples of ovarian surface epithelium
OFP-14-005 (OSE)]. Transition zones were taken separately for morphological assess-
Trefoil factor 2 (TFF2) as a surrogate marker for endocervical ment. Immunohistohemiscal investigation involved LGR5, NANOG,
gastric-type carcinoma LNX9, CD117, CD44 and Oct4 assessment. Statistics was done with
T. Kiyokawa1, L. Hoang2, C. Terinte3, A. Pesci4, S. Aviel-Ronen5, Student’s test with Boferroni correction.
I. Alvarado-Cabrero6 , E. Oliva 7 , K.J. Park8 , R.A. Soslow 8 , S. Results: LGR expressed in 38 fimbriae, 22 PFZ, 21 POZ, 32 OSEs;
Stolnicu9 NANOG expressed in 25 fimbriae, 20 PFZ, 24 POZ, 35 OSEs; LHN9
1
Department of Pathology, the Jikei University School of Medicine, expressed in 27 fimbriae, 19 PFZ, 19 POZ, 25 OSEs; CD 117 expressed
Japan, 2 Department of Pathology, Vancouver General Hospital, in 30 fimbriae, 10 PFZ, 15 POZ, 11 OSEs. Statistically significant differ-
Canada, 3 Department of Pathology, Oncologic Institute Iasi, Romania, ence in progenitor markers expression were shown between TZs, OSE
4
Pathology-IRCCS Ospedale Sacro Cuore-Don Calabria, Italy, and fimbriae, as well as between normal epithelium and HGSC and be-
5
Department of Pathology, Sheba Medical Center, Tel-Hashomer, tween TZs and epithelial cells elsewhere (р<0,05).
Israel, 6 Department of Pathology, Hospital de Oncología Mexico City, Conclusion: We investigated transitional zones of the uterine adnexa
Mexico, 7 Department of Pathology, Massachusetts General Hospital, with progenitor cell markers and revealed that there is a significantly
USA, 8 Department of Pathology, Memorial Sloan Kettering Cancer higher concentration of these cells in the transition zones where two types
Center, USA, 9 Department of Pathology, University of Medicine, of the epithelia met. Thus, these zones can be a potential source (hot spot)
Pharmacy, Sciences and Technology of Targu Mures, Romania for neoplasia development due to mutations in progenitor cells and further
clonal expansion.
Background & Objectives: Gastric-type carcinoma (GAS) is a distinct
subtype of endocervical adenocarcinoma (ECA), being the most common
HPV-unrelated type with an aggressive behavior. HIK1083 is a specific OFP-14-007
marker for GAS, but not highly sensitive and only available in Japan. Diagnostic panel with p16, stathmin1 and laminin-gamma1 for se-
TFF2 is a mucin associated peptide expressed in normal gastric but not rous tubal intraepithelial carcinoma
endocervical glands. This study was carried out to investigate whether A. Asaturova1, N. Kondrikov2
1
TFF2 could be a surrogate marker which in conjunction to HIK1083 FSBI 'National Center for Obstetrics, Gynaecology and Perinatology
could separate GAS from other types of ECA. named after V.I.Kulakov' Ministry of Healthcare Russian Federation,
Virchows Arch

Russia, 2 Moscow Regional Research Institute of Obstetrics and OFP-14-009

Gynaecology, Russia Immunohistochemistry with CK17 and SOX2, in addition to p53,
can be of diagnostic value for differentiated vulvar intraepithelial
Background & Objectives: Serous tubal intraepithelial carcinoma neoplasia (dVIN)
(STIC) is known to be a putative precursor for the most common and S. Dasgupta1, S. Koljenović1, H.C. van Doorn1, V. Noordhoek Hegt1, F.J.
aggressive ovarian carcinomas, namely ovarian high-grade serous carci- van Kemenade1, P.C. Ewing-Graham1
1
noma. Precise and early diagnose this disease is therefore one of the Erasmus MC, University Medical Centre Rotterdam, The Netherlands
priorities for tissue diagnosis in gynaecologic oncology. At the same time
routinely applied algorithm for STIC diagnosis could not cover some grey Background & Objectives: Differentiated VIN (dVIN) is a difficult
zones in its diagnostics. histological diagnosis, as it often resembles non-neoplastic epithelial dis-
Methods: The study included 70 patients (125 fallopian tubes), all orders (NNED), particularly lichen sclerosus (LS). We reviewed dVIN
of the specimens were investigated morphologically and cases from a retrospective cohort and explored additional diagnostic im-
immunohistochemically (р53, Ki-67, р16, stathmin1 and laminin- munohistochemical markers [i.e. Cytokeratin 17 (CK17) and SOX2].
gamma1). Statistics involved exact Fisher’s test, χ2-test, Cohen’s CK17 is a differentiation marker upregulated in squamous dysplasia,
kappa. and SOX2 is an onco-protein activated in squamous cell carcinoma.
Results: Expression of p16, stathmin1 and laminin-gamma1 was re- Methods: In total, 160 dVIN cases (2014 – 2017) from Erasmus MC
vealed in 85%, 77,5% and 90% of STIC consequently. In 4 tubes with were reviewed by two pathologists. Immunohistochemistry with CK17
STIC, only one of these tree markers was positive but we has no cases and SOX2, and conventional markers (p53, p16, MIB-1) was performed
with all three negative expression. In STIC cases, expression of р16, on a subset of cases comprising dVIN (n = 20), NNED (n = 9), normal
stathmin1 and laminin-gamma1 was high both in the presence and in vulvar tissue (n = 9). Receiver operating characteristic curves were
the absence of p53 expression in atypical cells. In most cases, positive plotted.
expression of at least two of the three studied markers was shown. p16, Results: The mean expression of CK17 (p = 0.03) and SOX2 (p = 0.01)
stathmin1 and laminin-gamma1expressin does not differ between p53- were significantly higher in dVIN compared to NNED and normal vulvar
positive and p53-negative STICs. Cohen’s kappa for STICs with am- tissue. Overexpression of p53 was seen in 60% of dVIN cases, 15%
biguous p53 expression was moderate (0.55) when we used only p53 showed null pattern, and 25% showed wild type expression. All dVIN
and ki-67 expression. P16/laminin-gamma1/stathmin1 diagnostic cases were p16 negative and showed increased MIB-1 expression in basal
panel let us increased Cohen’s kappa to good reproducibility (0.72), and suprabasal layers. The area under the curve of p53 was 0.78 for the
(p<0.05). diagnosis of dVIN, and that of p53, CK17, and SOX2 combined was 0.82.
Conclusion: Lack of grey zones in STIC diagnostics and good reproduc- Conclusion: Our preliminary results show that immunohistochemistry
ibility of diagnoses allows us to recommend p16, stathmin1 and laminin- with CK17 and SOX2 can be of diagnostic value for dVIN when used
gamma1 diagnostic panel for STIC diagnostics, especially in case of in a panel along with p53.
ambiguous p53 expression and/or borderline KI-67 expression.

OFP-14-010
OFP-14-008 Precursor lesions of vulvar squamous cell carcinoma - a systematic
Relationship between microcystic, elongated and fragmented pattern review
of myometrial invasion and histopathological prognostic factors in S. Dasgupta1, P.C. Ewing-Graham1, S.M. Swagemakers1, H.C. van
endometrioid endometrial carcinoma Doorn1, V. Noordhoek Hegt1, S. Koljenovic1, F.J. van Kemenade1
S.D. Altindag1, S. Yigit1, S. Sen2 1
Erasmus MC, University Medical Centre Rotterdam, The Netherlands
1
Izmir Katip Celebi University Ataturk Training and Research Hospital,
Department of Pathology, Turkey, 2 Izmir Katip Celebi University Background & Objectives: Vulvar intraepithelial neoplasia (VIN) is the
Ataturk Training and Research Hospital, Department of Gynaecology precursor lesion of vulvar squamous cell carcinoma (VSCC). In this sys-
and Obstetrics, Turkey tematic review we provide a detailed overview of the updated nomencla-
ture, histological diagnostic criteria, and available ancillary tools (immu-
Background & Objectives: Endometrioid endometrial carcinoma (EEC) nohistochemical and molecular) for the various VSCC precursors. With a
is generally has a favourable prognosis. Recently, many studies have view to identify additional diagnostic biomarkers for VIN, datasets from
claimed that microcystic, elongated, and fragmented (MELF) pattern of gene expression omnibus (GEO) were analysed.
myometrial invasion (MI) was associated with a poor prognosis. The Methods: Biomedical bibliographic databases were searched with elec-
purpose of this study is to examine relationship between MELF pattern tronic search strategies; citation and hand searching were also performed.
with histopathologic parameters in EEC. PRISMA guidelines were followed; the study was registered in
Methods: Hematoxylin and eosin slides of 234 cases of EEC with MI PROSPERO [CRD42019107290]. Whole genome sequencing datasets
(from 2009 to 2014) were evaluated retrospectively from pathology ar- of VSCC from GEO were imported into OmniViz for analysis.
chives. The association of MELF pattern with age, tumour grade, depth of Differential expression of genes was identified using statistical analysis
MI, presence of lymphovascular space invasion (LVSI), cervical stromal of microarrays (SAM). For functional annotation of microarray results,
invasion, lymph node metastasis, and International Federation of Ingenuity Pathway Analysis was used.
Gynaecology and Obstetrics (FIGO) stage was analysed. Results: The final selection comprised 105 references; a narrative syn-
Results: The mean age was 60.7 (33-83). Grade 1, 2, 3 were observed in thesis was prepared. HPV-associated usual VIN (uVIN) is characterised
142 cases (60.7%), 76 (32.5%) and 16 (6.8%) respectively. MELF pattern by overt nuclear atypia and p16 positivity, while HPV-independent dif-
was observed in 51 cases (21.8%). Presence of MELF pattern was sig- ferentiated VIN (dVIN) is characterised by p53 overexpression. A new
nificantly associated with deep (≥50%) MI (p<0.001), presence of LVSI potential VSCC precursor, differentiated exophytic vulvar intraepithelial
(p<0.05), lymph node metastasis (p<0.05), and advanced (III-IV) FIGO lesion (DEVIL), is characterised by PIK3CA mutation, and wild type p53
stage (p<0.05). expression. From the GEO analysis, the molecules SPRR2G, S100A7A,
Conclusion: In conclusion, MELF pattern invasion was found to be and KRT17P, were found to be most significantly upregulated in dVIN;
related statistically with deep MI, presence of LVSI, lymph node metas- these are involved in epidermal maturation and promotion of chemotaxis.
tasis, and advanced FIGO stage. Therefore, MELF pattern can be associ- The molecules OLFM4, MAL, and APOD were most significantly down-
ated with poor outcome. regulated in dVIN; these mediate cellular adhesions.
 Virchows Arch

Conclusion: Updated knowledge of VSCC precursors will facilitate re- Methods: We report a series of five cases with histopathological, immu-
producible diagnosis amongst pathologists. GEO dataset analysis pro- nohistochemical (p16) and PCR analyses. The cases as well as the pa-
vides newer insights into potential biomarkers for VSCC precursor le- tients previously published in the literature were reviewed for follow-up
sions. information.
Results: Thirteen cases were identified. The mean age of 47.1 years
(range 34 – 66) was not different from the usual type of cervical
OFP-14-011 AC. 10/13 cases presented with tumours >2cm and a polypoid-
Neuroendocrine tumours involving the cervix: the role of p16 and exophytic appearance. Regardless of tumour size and stage of the
HPV-genotyping disease, seven out of 11 patients developed recurrent disease after a
A. Varelas1, A.R. Lopes2, A. Tavares3, J. Ferreira1, R. Vieira1, R. Moreira mean of 7.8 months (range 6 weeks to 36 months). Five patients
Silva1, R. Dias1, R. Medeiros3, H. Sousa3, C. Bartosch4 developed distant metastases (three of them in the lungs). Five out
1
Portuguese Oncology Institute of Porto (IPO-P), Pathology Department, of the 11 informative cases died of the disease. All reported cases
Portugal, 2 Portuguese Oncology Institute of Porto (IPOP-P), Oncology were positive for high-risk HPV (mainly HPV type 18) and asso-
Department, Portugal, 3 Portuguese Oncology Institute of Porto (IPO-P), ciated with p16-overexpression.
Virology Department, Portugal, 4 Department of Pathology IPOP, Conclusion: i-SMILE represent a distinct subtype of invasive
Portugal endocervical AC, associated high-risk HPV-infection and strong p16-
overexpression. Clinically, i-SMILE may represent an aggressive tumour
Background & Objectives: Primary neuroendocrine carcinoma of the with early recurrent disease and substantial risk of distant metastatic dis-
cervix, albeit rare, is an important diagnostic to ascertain, as it may have ease, especially to the lungs.
particular therapeutic and prognostic consequences. This tumour has a
well-established association with HPV. We hypothesized that p16
immunoexpression and HPV-genotyping in a cervix neoplasia with neu- Oral Free Paper Sessions One-Day CPS
roendocrine differentiation may be useful to distinguish primary from
secondary origin. and Two-Day MDS
Methods: We reviewed clinicopathological features of 25 patients with
neuroendocrine tumours involving the cervix diagnosed at Portuguese
Oncology Institute of Porto (1989-2019). Immunohistochemical profile Sunday, 8 September 2019, 17:15 - 19:15, Clio
(including neuroendocrine markers and p16) was evaluated and tumours’
CP-03 | 1-Day Computational Pathology
HPV-genotyping was performed.
Symposium – Selected Abstracts
Results: Patients had a median age of 59(range 25-78) years. Tumours
had a median size of 7 (range 3.5-10) cm. Regarding stage at diagnosis,
14(56%) were confined to the cervix, 9(36%) had disseminated disease CP-03-001
and 2(8%) were unknown. Diagnostic samples were mostly limited to Deep learning enables fully automated mitotic density assessment in
biopsies(n=20) and 5 patients had hysterectomy specimens. Most were breast cancer histopathology
small cell neuroendocrine carcinomas(n=23) and 2 had features of large M. Balkenhol1, P. Bult1, D. Tellez1, W. Vreuls2, P. Clahsen3, F. Ciompi1,
cell neuroendocrine carcinoma. All tumours showed at least J. van der Laak1
1
chromogranin (20/23) or synaptophysin (17/20) expression; p16 was dif- Radboud University Medical Center, The Netherlands, 2 Department of
fusely positive in 18/24 and correlated with HPV status in most cases (14/ Pathology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands,
3
20). HPV was detected in 16 tumours (including HPV-18 and/or 16), 4 Haaglanden Medical Center, The Netherlands
were HPV negative and 5 inconclusive. Within negative HPV tumours,
one largely extended to the endometrium, one had a synchronous ovarian Background & Objectives: Mitosis counting is an important part of
mass, and two had disseminated disease with liver, lymph node and bone breast cancer grading, yet known to suffer from observer variabil-
involvement. ity. Advances in machine learning enable fully automated analysis
Conclusion: When evaluating a tumour with neuroendocrine differenti- of digitized glass slides. The present study evaluated automatic
ation, HPV-negativity, with or without p16 immunoexpression, may fa- mitosis counting and demonstrated applicability on triple negative
vour a secondary involvement of cervix, prompting for further diagnostic breast cancers (TNBC).
studies. Methods: A deep learning algorithm fully automatically detected
mitoses in scanned H&E slides of 90 invasive breast tumours and
determined the mitotic hotspot. Two independent observers assessed
OFP-14-012 mitotic density on glass slides according to routine practice, and in
Invasive stratified mucin producing carcinoma of the uterine cervix - the computer-defined hotspot. Automated mitotic counting was also
an unusual tumour with aggressive behaviour performed in a TNBC cohort (n=597). Cox regression models were
L. Horn1, R. Handzel2, U. Siebolts3, C.E. Brambs4 expanded with dichotomized mitotic counts, using the c-statistic to
1
Institute of Pathology, Germany, 2 Division of Gynaecologic Oncologic evaluate the additional prognostic value of every possible cut off
Surgery, Department of Obstetrics and Gynaecology (Institute of Trier), value.
University Hospital Leipzig, Germany, 3 Division of Molecular Results: Automatic counting showed excellent concordance with vi-
Pathology, Institute of Pathology, University Hospital Halle/Saale, sual assessment in computer detected hotspots with intraclass cor-
Germany, 4 Department of Obstetrics and Gynaecology, Technical relation coefficients (ICC) of 0.895 (95% CI 0.845–0.930) and
University Munich, Germany 0.888 (95% CI 0.783–0.936) for two observers, respectively. ICC
of fully automated counting versus conventional glass slide assess-
Background & Objectives: Invasive stratified mucin-producing carci- ment were 0.828 (95% CI 0.750–0.883 and 0.757 (95% CI 0.638–
noma (i-SMILE) represents a recently recognized subtype of cervical 0.839), respectively. In the TNBC cohort, none of the cut off values
adenocarcinoma (AC) developing in a background of a stratified improved the models’ baseline c-statistic.
mucin-producing intra-epithelial lesion (SMILE). Clinical and prognostic Conclusion: Automatic mitosis counting is a promising complemen-
data on i-SMILE are limited. Here we report a case series and review the tary aid for mitoses assessment. Our method was capable of fully
literature regarding prognostic outcome. automatically locating the mitotic hotspot in tumours, and was
Virchows Arch

capable of processing a large series of TNBC, showing that mitotic appearance. We use generative adversarial networks to solve the
count was not prognostic for TNBC even when attempting alterna- problem of creating an adequately representative model of appear-
tive cut off points. ance, while at the same time learning a generative and discriminative
component. We use information from both image space and latent
This study was funded by a Junior Researcher grant from the Radboud space to differentiate between observations that conform to the train-
University Medical Center Institute for Health Sciences (RIHS). ing data and such data that does not fit.
Results: The trained model is able to generate images that are visually
similar to the non-tumour images. In the case of anomalous images
CP-03-002 (contain metastases), the pairs of input images and generated images
Automated grading of urothelial cell carcinoma of the bladder show significant differences. The distributions of the anomaly score
I. Jansen1, M. Lucas1, J. Bosschieter2, S. Meijer3, O. de Boer3, T. van over non-tumour images from the training set and test set or over
Leeuwen4, H.A. Marquering4, J.A. Nieuwenhuijzen2, D.M. de Bruin4, images extracted from metastatic cases show that the anomaly score
C.D. Savci-Heijink4 is suitable for the classification of normal and anomalous samples
1
Department of Biomedical Engineering and Physics, Amsterdam UMC, (P<0.001).
University of Amsterdam, The Netherlands, 2 Amsterdam UMC, location Conclusion: We presented an unsupervised approach for colorectal me-
VUmc, The Netherlands, 3 Department of Pathology, Amsterdam UMC, tastasis detection in liver biopsies. Training patches were extracted from
University of Amsterdam, The Netherlands, 4 Amsterdam UMC, location non-tumour images; avoiding the necessity of having detailed pathologist
AMC, The Netherlands annotation. The approach may be applied across the whole range of
computational pathology problems.
Background & Objectives: Although histological grade is an important
predictor for recurrence and progression in non-muscle invasive bladder
cancer (NMIBC), the reproducibility is low. CP-03-004
The aim of this study is to investigate the potential value of a deep Automated Ki67 hot-spot detection and analysis leads to higher Ki67
learning architecture for the grading of urothelial cell carcinoma (UCC) proliferation indices
of the bladder using histology slides of transurethral resection of bladder M. Zwager1, T. Koopman1, H. Buikema1, D. Omanovic2, A. Schønau2,
tumour (TURBT) specimen and assess its accuracy by the comparison H. Klingberg2, B. van der Vegt1
1
with the consensus grading of three pathologists. University of Groningen, University Medical Center Groningen,
Methods: Histological glass slides of patients with NMIBC who The Netherlands, 2 Visiopharm A/S, Hørsholm, Denmark
underwent a TURBT between 2000-2016 in three hospitals in the
Netherlands were included. The slides were independently reviewed by Background & Objectives: It is suggested that Ki67 proliferation hot-
three pathologists, assigning the WHO’73 and WHO’04 grade, resulting spot scoring is a prognostic and predictive marker in breast cancer.
in a four-tiered grading scheme. The slides were digitized, manually anno- However, visual identification of Ki67 hot-spots is difficult and manual
tated by an expert observer and subsequently checked by a uropathologist. scoring is labour-intensive and prone to inter- and intra-observer variabil-
Firstly, a U-Net was trained to segment urothelium. Based on these seg- ity. Automated detection and scoring of Ki67 hot-spots by digital image
mentations, an ImageNet pre-trained DenseNet was trained for automated analysis (DIA) could aid in a standardised and reproducible assessment of
grading of the urothelial lesions based on the consensus score of the three the Ki67 proliferation index. The aim of this study was to compare man-
pathologists. ual Ki67 hot-spot detection and scoring with DIA Ki67 hot-spot detection
Results: In total, 328 tissue samples of 232 patients were included. In and scoring.
93% of the slides, the urothelium was accurately detected. In another 21% Methods: Whole tissue sections of 117 consecutive invasive breast
false positive regions were detected. Incorrect classification was mainly carcinomas were immunohistochemically stained for Ki67. Firstly,
in slides with extensive color loss or in regions with inflammation. Ki67 hot-spots were detected by two independent observers and
Detailed data on the UCC grading will be presented at the conference. scored using a validated manual counting protocol. Secondly, man-
Conclusion: This feasibility study demonstrates the potential value of ual Ki67 scores were compared with DIA on these manually anno-
deep learning methods in classification of urothelial lesions. tated hot-spots. Thirdly, automated Ki67 hot-spot detection and
Ki67 calculation was performed using DIA. Inter-observer agree-
I Jansen and M Lucas are paid by ITEA3. Grant number: ITEA151003. ment between manual scores and DIA in manually annotated hot-
spots, and between manual observers was assessed using the coeffi-
cient of determination (R2). Means of manual scoring and DIA re-
CP-03-003 sults were compared.
Unsupervised anomaly detection: application to colorectal liver Results: 102 cases were available for assessment. Correlation between
metastasis both manual observers was suboptimal (R2=0.78). Manual and DIA Ki67
A. Serag1, P. Maxwell2, J. Diamond1, A. Ion-Margineanu1, A. Kennedy1, scores in manually annotated hot-spots showed a strong correlation
R. McMillan1, H. Qureshi1, M. Saint Martin1, M. Salto-Tellez2, P. (R2=0.90). Hot-spot detection by DIA (mean: 39.0%) led to higher hot-
Hamilton1, P. O'Reilly1 spot scores compared to manual scoring (means: 33.4% and 29.4%).
1
Philips Digital & Computational Pathology, United Kingdom, 2 Queen's Conclusion: Automated Ki67 hot-spot detection and analysis is a reliable
University Belfast, United Kingdom method that leads to higher hot-spot Ki67 proliferation indices.

Background & Objectives: The building of deep learning models needs

large amounts of data with annotated examples. Obtaining expert labels CP-03-005
for such models is difficult since detailed annotation is time-consuming. U-Net ensembles for accurate classification of oesophageal
Here, we present an unsupervised learning approach capable of identify- adenocarcinoma
ing anomalous patterns that can serve as imaging biomarker candidates. B. Cardenas Guevara1, V. van Oijen1, D. Worrall1, K. de Laat2, M. van
We show the application of the proposed approach for detecting colorec- der Wel2, M. Lucas3, I. Jansen3, H. Marquering3, D. de Bruin3, D. Savci-
tal metastases in liver biopsies. Heijink2, O. de Boer2, S. Meijer2
1
Methods: We propose to use unsupervised learning to create a rich Amsterdam Machine Learning Lab, University of Amsterdam,
generative model of normal (i.e. non-tumour) local anatomical The Netherlands, 2 Department of Pathology, Amsterdam UMC,
 Virchows Arch

University of Amsterdam, The Netherlands, 3 Department of Biomedical urine cytology (n=624) and whole slide CRC specimens (n=173). H&E
Engineering and Physics, Amsterdam UMC, University of Amsterdam, labelled whole slides of CRC were analysed using AI after both pathology
The Netherlands trained feature recognition (n=650) and without any human direction (n=75).
Results: Bladder cancer diagnosis was reported from urine cytology
Background & Objectives: Oesophageal adenocarcinoma has a dismal samples with 95% sensitivity and 70% specificity. CRC survival
prognosis and Barrett’s oesophagus (BE) is the only known precursor was predicted with an AUROC of 0.94 in the immunofluorescence
lesion. BE progresses through a metaplasia-dysplasia-carcinoma se- labelled cohort using 123 automatically extracted features and with
quence. Progression rates from non-dysplastic BE (NDBE) are low >95% accuracy in the H&E stained digitised slides when applying
(0,5%), but a histopathological diagnosis of low grade dysplasia (LGD) no human input.
is a strong independent risk factor for progression. As a result of signif- Conclusion: The use of AI allows clinically significant features to be
icant interobserver variation, reported progression rates vary from 1- 40% reported with or without human training and error. This work demon-
and therefore International guidelines mandate a second opinion by an strates AI’s ability to automatically report clinical specimens and how
expert-pathologist. the technology can track toward clinical translation such as with the
We aim to develop a convolutional neural network for objective and iCAIRD initiative.
reproducible diagnosis of dysplasia in BE at expert-pathologist level.
Methods: TIFF images from 400 digitized biopsies of 170 BE pa-
tients were annotated in high detail by an expert pathologist, gener- CP-03-007
ating binary classification masks for NDBE and dysplastic glands. Implementation of the ContextVision INIFY(TM) tool for the auto-
Patches of the H&E staining and corresponding binary mask were matic detection of prostatic cancer in a fully digital routine workflow
extracted, resulting in 148.033 and 34.557 patches for training and F. Fraggetta1, S. Lionti1, G. Giuffrida1, C. Emmanuele1, P. Pepe2
1
testing, respectively. An ensemble of U-Nets was used, using a com- Pathology Unit Cannizzaro Hospital, Italy, 2 Urology Unit Cannizzaro
bination of the U-Net architecture with DenseNet and ResNet Hospital, Italy
models, pre-trained on ImageNet. The ensemble consisted of four
U-Nets with a down-sampling path using the DenseNet architecture Background & Objectives: Validation of an Artificial Intelligence (AI)
and four other U-nets using the ResNet architecture. As metrics F1 prototype tool INIFYTM (ContextVision Company, Sweden) for the de-
coefficient and the pixel-wise accuracy was used. tection of prostatic cancer in bioptic samples were evaluated ia fully
Results: F1 scores (range 80.6 and 84.9%) and pixel-wise accuracy digital pathology laboratory at Cannizzaro Hospital in Catania, Italy
(range 86.5 to 90.6%) of individual models and combinations; the best Methods: The procedure included the following steps: integration with
performing combination was the ensemble consisting of a committee of the local laboratory information system (LIS) (Pathox ver.13) and possi-
eight DenseNet and ResNet models. bility to open the INIFYTM web viewer. All cases submitted were con-
firmed by expert pathologists.
Results: The integration with the local LIS was obtained using a specific
Model F1-score Pixel-wise accuracy HL7 connection. between LIS and INIFYTM AI tool without problems.
According to a default protocol only Whole Slide Images (WSI) belonging
U-Net 80,6% 86,5% to prostatic bioptic samples were automatically submitted for analysis at the
end of the scanning session, without need of manual intervention. After
U-Net + ResNet-34 81.9 % 87.6 % analysis the results were available within the virtual tray of the case: flipped
U-Net + ResNet-152 83.1 % 88.9 % image if cancer. A total of 4746 WSI of prostatic cancers were submitted to
U-Net + DenseNet-161 82.8 % 88.1 % INIFYTM tool, with a success rate of 100%. The prototype tool showed
high specificity at recognizing cancer but low sensitivity. However by using
Ensemble DenseNet and ResNet 84.9 % 90.6 %
the INIFYTM viewer all the suspicious area were indicated.
Conclusion: The installation of ContextVision INIFYTM in the Catania
Conclusion: U-Net ensembles that classify precursor lesions of oesoph- Digital Pathology department showed a successful integration of this AI
ageal adenocarcinoma can be used for accurate risk stratification of pa- tool in a fully digital workflow, facility to use, working as computer-aided
tients with BE. diagnosis. This tools could be a helpful instrument in a digital routine.

Monday, 9 September 2019, 08:30 - 09:30, Clio

CP-03-006
Artificial intelligence driving automated pathology: iCAIRD and MD-01 | 2-Day Molecular Diagnostics Symposium –
beyond Selected Abstracts
P. Caie1, N. Dimitriou1, I.P. Nearchou1, O. Arandjelović1, D. Harrison1
1 MD-01-001
University of St Andrews, United Kingdom
Plasma cfDNA testing of patients with EGFR mutant non-small cell
Background & objectives: Artificial Intelligence (AI) can be trained to lung cancer: droplet-digital PCR versus next-generation sequencing
recognise complex patterns and morphology within digitised histopatholo- compared to tissue-based results
gy specimens and use them to aid clinical reporting. These patterns may be C.M. Steendam1,2, P.N. Atmodimedjo1, E. de Jonge1, M.S. Paats1, C. van
already known, where the pathologist trains the AI model. However, cancer der Leest2, E. Oomen - de Hoop1, J.H. von der Thüsen1, W.N. Dinjens1,
is a complex disease and the tissue may harbour undiscovered but clinically R.H. van Schaik1, J.G. Aerts1, H.J. Dubbink1
1
significant morphological patterns. AI can also be used to identify and Erasmus MC, Rotterdam, The Netherlands, 2 Amphia Hospital, Breda,
report such novel features without human bias and error. This talk will The Netherlands
demonstrate how the two above methodologies were successfully used in
colorectal (CRC) and bladder cancer examples and how they will be used Background & Objectives: To compare the results of plasma cell-free
for the automatic reporting of gynaecological specimens in the iCAIRD DNA (cfDNA) droplet-digital PCR (ddPCR) and next generation sequenc-
initiative. ing (NGS) on detection of Epithelial Growth Factor Receptor (EGFR)
Methods: Machine learning workflows were designed to analyse unbiasedly primary activating mutations and p.T790M with results of tissue analysis
extracted data from the automated analysis of immunofluorescence labelled in patients with EGFR mutated non-small cell lung cancer (NSCLC).
Virchows Arch

Methods: All patients with EGFR mutated NSCLC for which a pa- in detectability of variants in cfDNA comparing to quality of sam-
thology and a plasma specimen were available upon progression ple. TP53 variants in healthy resident of ESCC endemic area war-
between November 2016 and July 2018 were selected. rants further investigation.
Concordance, Cohen’s kappa and intraclass correlation coefficients
were calculated.
Results: Plasma cfDNA and pathology specimens of 36 patients were MD-01-003
analysed. Agreement between ddPCR and NGS was 86% (κ=0.63) Global delivery of external quality assessment for lung cancer liquid
for the primary activating mutation and 94% (κ=0.89) for p.T790M biopsy testing
detection. Allele ratios were comparable with an intraclass correla- J. Fairley1, M. Cheetham2, M. Denis3, E. Dequeker4, C. Keppens4, F.
tion coefficient of 0,992 and 0,997 respectively. Discrepancies of Fenizia5, N. Normanno5, S. Patton6, E. Rouleau7, E. Schuuring8, K.
some degree were found in 15 patients (41.7%). In 6 patients Van Casteren9, Z. Deans1
1
(16.7%), no mutations at all were detected in cfDNA. In 3 patients GenQA/UKNEQAS, United Kingdom, 2 EMQN, United Kingdom,
3
(8.3%), p.T790M was detected in plasma but not in pathology spec- Gen&Tiss, France, 4 ESP, Belgium, 5 Istituto Nazionale Tumouri
imen, while in 3 other patients (8.3%), p.T790M was demonstrated in "Fondazione Giovanni Pascale", IRCCS, Naples, Italy, 6 European
the pathology specimen but not in plasma. Concordance of cfDNA Molecular Genetics Quality Network (EMQN), Manchester Centre for
and pathology for the primary activating mutation was 69% for Genomic Medicine, St Mary's Hospital, United Kingdom, 7 Department
ddPCR and 83% for NGS. For the detection of p.T790M this was of Pathology and Medical Biology, Institut Gustave Roussy, Villejuif,
75% (κ=0.49) for ddPCR as well as for NGS. France, 8 ESP, The Netherlands, 9 Biomedical Quality Assurance
Conclusion: Mutual agreement is high between NGS and ddPCR in Research Unit, KU Leuven, Belgium
cfDNA on the level of a specific mutation, with comparable ratio results.
Plasma testing of EGFR primary activating mutations and p.T790M Background & Objectives: Wide-spread implementation of cell free
shows high concordance with pathology results, for NGS as well as DNA (cfDNA) testing of plasma for cancer mutations requires quality
ddPCR, depending on the extent of the panel used. In NGS, more genetic assessment of these services to ensure patient safety. The international
aberrations can be investigated at once. external quality assessment (EQA) provider consortium, IQNPath has
delivered a second successful EQA run to determine the standard of
This work was supported by AstraZeneca. cfDNA testing for lung cancer.
Methods: Five European EQA providers, under the umbrella of
IQNPath, collaborated to deliver the assessment during 2018-19 to a
MD-01-002 total of 320 laboratories from 44 countries. A panel of bespoke
Circulating cell-free DNA in archived low-quality volume serum manufactured plasma samples with varying mutations at a range of
samples: rate of concordance with mutation in tumour allelic frequencies were validated by a range of methodologies prior
D. Nasrollahzadeh1, B. Abedi-Ardekani1, T. Delhomme1, P.H. Avogbe1, to distribution to ensure stability and reproducibility. The EQA sam-
M. Foll1, J. McKay1, P. Brennan1, R. Malekzadeh2 ples were supplied for testing and reporting according to laboratory
1
International Agency for Research on Cancer/WHO, France, 2 Digestive routine protocols. Peer reviewed criteria was applied to assess the
Disease Research Institute Tehran, Iran standard of genotyping and reporting.
Results: The genotyping accuracy, variability of reporting content
Background & Objectives: Cell-free DNA (cfDNA) is considered as and formats will be discussed. Low allelic frequency samples were
non-invasive method for cancer detection with high specificity and the most challenging and some methods did not detect these muta-
variable sensitivity. Mainstream cfDNA studies are based on quali- tions. Reporting of such cases often did not address the risk that
fied samples which is plasma kept at -80, with no cycle of re-thawing, tumour DNA may have not been tested and limitations of the testing
and minimum volume of 1 ml. In some archival studies, such stan- performed was not addressed when reporting the result.
dards were not met. We aim to investigate feasibility of cfDNA de- Conclusion: The variability in the standard of genotyping and reporting
tection in archival serum samples kept at -20 with several cycles of highlights the need for EQA in this field and educational guidance to
re-thawing and volume less than or equal to 0.7 ml. ensure the delivery of high-quality clinical service where testing of
Methods: Leftover sera from a population-based study of oesophageal cfDNA is the only option for clinical management.
squamous cell carcinoma (ESCC) in Northern Iran- conducted 14 years
ago- were used. Sera were applied for several serology assays and
underwent between 4 and 6 cycles of re-thawing. TP53 mutation data MD-01-004
from formalin-fixed paraffin-embedded ESCC tissues was available for Reflex tumour BRCA1/2 testing in ovarian carcinomas to stratify
one-third of the cases. We extracted cfDNA from 44 ESCC and 39 con- PARP inhibitor treatment and germline diagnostics
trols (matched for storage condition). 27 TP53 amplicons were deep M. Ligtenberg1, J.R. Vos2, I.E. Fakkert2, J.A. de Hullu3, A.M. van
sequenced on ion-torrent platform. Needlestack, a pipeline for calling Altena3, A.S. Sie2, H. Ouchene2, R.W. Willems1, I.D. Nagtegaal1, M.C.
variants with extremely low allelic fraction (AF) was applied. RVSB Jongmans2, A.R. Mensenkamp2, G.H. Woldringh2, J. Bulten1, E.M.
>0.85, Q-value<30, and minimum distance form highest AF <10 nt. were Leter4, C.M. Kets2, M. Simons1, N. Hoogerbrugge2
1
filtered. Department of Pathology, Radboud University Medical Center,
Results: We were able to detect 20% of tumour tissue mutations concor- Nijmegen, The Netherlands, 2 Department of Human Genetics,
dantly in CfDNA of archival sera. After applying filtrations, 59 unique Radboud University Medical Center, Nijmegen, The Netherlands,
3
mutations were detected in all cfDNAs, out of them 24 were exclusively Department of Obstetrics and Gynaecology, Radboud University
detected in ESCC cases and 29 found just in controls. None of the tumour Medical Center, Nijmegen, The Netherlands, 4 Department of
mutations was detected among controls. One likely non-germline cfDNA Clinical Genetics, Maastricht University Medical Center,
mutation was detected in both case and control which had significantly The Netherlands
higher AF in case than control.
Conclusion: Applying our method, detection rate of concordant Background & Objectives: Women with ovarian carcinoma have a
TP53 mutations in archived low- volume sera and cancerous tissue higher chance to benefit from PARP inhibitor therapy if their tumour
is comparable to results of the same gene in well-kept plasma. has a somatic or germline BRCA1/2 pathogenic variant. Germline
These results suggest the crucial role of bioinformatics pipeline BRCA1/2 testing allows therapeutic and preventive choices in patients
 Virchows Arch

and family members. This study evaluates the feasibility, effectiveness, avoiding possible complications and limitations of tissue sampling in
and appreciation of reflex tumour BRCA1/2 testing in newly diagnosed pancreatobiliary cancers. Although primary diagnosis still needs histolog-
ovarian carcinoma patients to stratify patients for PARP inhibitor therapy ic confirmation, liquid biopsies obtained from bile enable disease moni-
and predisposition testing. toring (e.g. in primary non-resectable cancers) using less invasive
Methods: Reflex tumour BRCA1/2 testing of newly diagnosed ovarian procedures.
carcinomas was evaluated in seven hospitals between October 2015 and
June 2017. Diagnostic yield, uptake, referral rates for genetic testing, and
Tuesday, 10 September 2019, 08:30 - 09:30, Clio
experiences of patients and gynecologists were evaluated.
Results: Reflex tumour BRCA1/2 testing was performed for 315 MD-05 | 2-Day Molecular Diagnostics
(78%) of 406 eligible samples and was successful in 305 (97%). In Symposium – Selected Abstracts
51 ovarian carcinomas a pathogenic BRCA1/2 variant was detected
(17%). Genetic counseling and germline testing was performed in 44
MD-05-001
patients, revealing that 57% of the mutations were hereditary. Most
Differentially expressed immune related genes in metastatic vs. non-
participating gynecologists and patients were positive about the
metastatic LUMA, LUMB1 and TNBC primary breast carcinoma
workflow.
cases
Conclusion: Reflex tumour BRCA1/2 testing in all newly diagnosed
A.M. Tokes1, O. Rusz1, C. Pollner-Szundi1, L. Madaras1, A. Kovács1, B.î
ovarian carcinoma patients to find somatic and germline BRCA1/2
Molnár2, I.î Vári-Kakas3, J. Kulka1
variants is feasible, effective and appreciated by patients and gyne- 1
Semmelweis University Budapest, 2nd Department of Pathology,
cologists. It serves as an effective pre-screen for genetic counselling
Hungary, 2 Semmelweis University Budapest, 1st Department of
and germline diagnostics. It extends personalised treatment choices
Surgery, Hungary, 3 University of Oradea, Department of Computers
based on tumour BRCA1/2 status to patients with somatic pathogen-
and Information Technology, Romania
ic variants and patients that do not opt for hereditary testing.
Background & Objectives: It is increasingly clear that tumour progres-
This work was financially supported by AstraZeneca and is presented on
sion largely depends of the cancer cell–stromal immune cell environment
behalf of the OPA working group.
interaction. The aim of the study is to define the immune gene signature
associated with metastatic potential of LUMA, LUMB1 and TNBC cases
by using Nanostring technology.
MD-01-005
Exploitation of cfDNA extracted from bile as liquid biopsy source in Methods: We compared mRNA levels of 730 immune-related genes by
pancreatobiliary cancers using Nanostring technology in 35 primary breast carcinoma (BC) cases
C. Driescher1, K. Ebner2, W. Goering1, L. Haeberle1, V. Keitel2, D. (12 LUMA (6 non-metastatic (NM) and 6 metastatic (M) BC), 11
Haeussinger2, I. Esposito1 LUMB1 (5NM and 6M) and 12 TNBC (6NM and 6M)) presenting
1
Institute of Pathology, Heinrich Heine University and University ≥1% stromal TIL and with a minimum 6 year available follow up data.
Hospital, Düsseldorf, Germany, 2 Department of Gastroenterology, TIL was assessed on HE stained slides.
Hepatology and Infectious Diseases, Heinrich Heine University and Results: The highest TIL ratio was observed in NM TNBC cases (mean-
University Hospital, Düsseldorf, Germany 9, 66%) and the lowest in M LUMA cases (mean 1,16%). In M LUMA
BCs compared to NM LUMA BCs we observed differences in genes
Background & Objectives: To date, accepted biomarkers in mostly related to chemokines, cytokines and cell functions. Whereas
pancreatobiliary cancers lack sensitivity and specificity and diagno- CXCL14, CCL3L1, CCL28 considered to be associated with metastases
sis often requires invasive procedures. Therefore, there is an urgent presented higher expression in M LUMA BCs, BTLA, LTA, and GZMB
need for reliable biomarkers allowing easy and repeatable sampling were detected in lower amount. The significantly different gene set in
to ensure dynamic real-time evaluation of tumour biology. metastatic vs. non metastatic LUMB1 BCs and TNBCs was more hetero-
Compared to classic histopathological analysis, liquid biopsy is a geneous compared to LUMA BCs. Significantly upregulated genes in
less-invasive method, which detects cell-free DNA (cfDNA) re- metastatic LUMB1 BCs and TNBCs compared to non-metastatic ones
leased into body fluids from primary or metastatic tumours. were VEGFA, CLEC5A, CCL28, CFB in LUMB1 and DUSP4, PPARG,
cfDNA contains tumour-specific aberrations with possible prognos- GATA3, ALCAM in TNBC cases.
tic and predictive value. Conclusion: Genes involved in cancer immunity most probably related
Methods: We extracted cfDNA from bile obtained from patients with to tumour progression vary considerably among breast carcinoma sub-
pancreatobiliary cancers (n=12) during routine diagnostic proce- types. The involvement of chemokines and their receptors in breast can-
dures. Tumour-specific aberrations were detected by next generation cer metastasis is only partly clear and needs further investigation.
sequencing using a panel of 50 oncogenes and tumour suppressor
genes on a S5 Sequencing platform. Matched tumour tissue (n=7) NVKP_16-1-2016-0004
served as control.
Results: Sequencing of cfDNA obtained from bile showed concor-
dance with somatic mutations found in tumour tissues in 92% of MD-05-002
cases. Eleven out of twelve mutations found in the tumour tissue Tumour mutational burden analysis: implementation in routine
were concordantly present in cfDNA sequencing results. In one case, diagnostics
an additional KRAS mutation was found in cfDNA, showing the L. Kroeze1, E. Kamping2, D. von Rhein2, E. Jansen2, R. de Voer2, M.
ability of liquid biopsies to better display tumour heterogeneity. In Barberis3, J. Botling4, E. Garrido-Martin5, F. Haller6, L. Lacroix7, B.
cases were sequencing from tissue failed, e.g. due to insufficient Maes 8 , S. Merkelbach-Bruse 9 , V. Pestinger 10 , N. Pfarr 11 , A.
DNA quality, cfDNA analysis could provide information about the Stenzinger12, K. Grünberg1, M. Ligtenberg1
1
mutational status of the tumour. Department of Pathology, Radboud University Medical Center,
Conclusion: Overall, cfDNA sequencing provided additional informa- Nijmegen, The Netherlands, 2 Department of Human Genetics,
tion about tumour heterogeneity and sufficiently replaced tissue sequenc- Radboud University Medical Center, Nijmegen, The Netherlands,
3
ing when aforementioned was not feasible. Therefore, cfDNA sequencing Division of Pathology and Laboratory Medicine, European Institute of
of bile represents a reliable method for detecting tumour mutations Oncology, Milan, Italy, 4 Department of Immunology, Genetics and
Virchows Arch

Pathology, Uppsala University, Sweden, 5 Instituto de Investigación, important signalling pathways was performed with the nCounter
University Hospital 12 de Octubre, Spanish National Center for Cancer PanCancer Pathways panel. Furthermore, the effect of HDACi on key
Research (CNIO) and CIBERONC, Madrid, Spain, 6 Institute of immunotherapy targets was investigated using a customised NanoString
Pathology, University Hospital Erlangen, Germany, 7 Department of expression panel.
Medical Biology and Pathology, Institute Gustave Roussy, Villejuif, Results: We could show that HR23b dependent sensitivity towards
France, 8 Laboratory for Molecular Diagnostics, Department of Clinical HDACi is mediated by apoptosis induction via death receptor pathways.
Biology, Jessa Hospital, Hasselt, Belgium, 9 Institute of Pathology In contrast, HR23b loss reduces apoptosis induction and shifts response
University Hospital of Cologne, Germany, 10 Institute of Cancer & to autophagy. Furthermore, we observed a significant upregulation of
Genomic Science, University of Birmingham, United Kingdom, 11 anticancer immunotherapy targets (e.g. cancer testis antigens) enhancing
Institute of Pathology, Technical University Munich, Germany, 12 the response to immunotherapy agents.
University Hospital Heidelberg, Germany Conclusion: Understanding key pathways of HDACi induced apoptosis
and the importance of HR23b as a predictive biomarker should help to
Background & Objectives: Although the introduction of immuno- select patients who may benefit from HDACi therapy. Especially the
therapy has benefitted many patients, more than half of the patients ability to enhance the endogenous antitumour activity as well as the
show no clear evidence of response, underlining the urge for new upregulation of possible immunotherapy targets might enable promising
predictive biomarkers. Recent studies show that, in addition to combinatorial treatments.
PDL1 expression and microsatellite instability (MSI), tumour muta-
tional burden (TMB; number of mutations/Mb) is an important novel
biomarker that improves the selection of patients who could benefit MD-05-004
from immunotherapy. MET exon 14 skipping mutations in non-small cell lung cancer: effi-
Methods: The TruSight Oncology 500 assay (TSO500, 523 cancer- cient routine diagnostics, histopathology and clinical response upon
related genes, 1.94Mb, Illumina) was tested for the determination of targeted treatment
TMB, MSI, mutations and copy number variations (CNVs) on W. Geurts-Giele1, M. Pruis2, J. von der Thusen3, I. Meijssen1, W.
formalin-fixed paraffin-embedded material (n=55) Dinjens4, J. Aerts3, M. Lolkema2, M. Paats5, H.J. Dubbink6
1
Results: Our validation indicates that the assay can clearly discrimi- Pathology, Erasmus MC Cancer Institute, The Netherlands, 2 Medical
nate between samples with low (normal tissue) and high TMB. Use Oncology, Erasmus MC Cancer Institute, The Netherlands, 3 Erasmus
of 40 ng DNA is recommended, but results using 15 ng are compa- Medical Center, Rotterdam, The Netherlands, 4 Erasmus University
rable. All known CNVs (n=9) and pathogenic mutations (n=59) were Rotterdam, Netherlands, 5 Pulmonary Diseases, Erasmus MC Cancer
detected, although 2 out of 6 complex indels (45 and 48 nucleotides) Institute, The Netherlands, 6 Erasmus MC, Rotterdam, The Netherlands
were not annotated by the TSO500 bio-informatic pipeline.
Furthermore, our validation shows that the tumour cell percentage Background & Objectives: Non-small-cell lung cancer (NSCLC) is one
can influence the TMB value; a biological problem unrelated to the of the solid malignancies with the most evolved personalised treatments
assay, but caused by heterogeneity of the variant allele frequencies based on molecular characteristics of the tumour. Mutations in EGFR,
due to an underlying deficiency in DNA repair. The TMB analysis is HER2 and BRAF, translocations of ALK, ROS1, RET and amplification of
highly reproducible within and among laboratories (n=11), for which MET all lead to specific treatment options. Recently, in 2-4% of lung
DNA from a third party was used. adenocarcinoma MET gene mutations leading to skipping of exon 14
Conclusion: The TSO500 assay can be used to perform comprehensive were found, making patients eligible for treatment with MET tyrosine
genetic analysis (mutations, CNVs, MSI and TMB) in a single assay kinase inhibitors. We will present our experience with routine detection
using only 15 ng of DNA and can replace current more targeted NGS of MET exon 14 skipping mutations, histological features of MET mutat-
analyses. ed tumours and clinical follow-up of these patients.
Methods: Since 2015 our custom-made DNA-based pan-cancer NGS pan-
This work was supported by Illumina, Bristol-Myers Squibb. el for routine molecular diagnostics was supplemented with four amplicons
for detection of MET exon 14 skipping mutations. Putative MET exon 14
skipping mutations were evaluated for their effect on splicing by RT-PCR if
MD-05-003 sufficient tissue was available. Histopathological characteristics and clinical
Role of HR23b in response to HDAC inhibitors and their effect on follow-up were investigated for all MET mutated NSCLC. Mutation fre-
immunotherapy targets quency was calculated including all routine diagnostic requests on NSCLC
S. Wagener-Ryczek1, C. Alidousty1, C. Heydt2 , J. Fassunke1, S. for therapeutic purposes from January 2016 to May 2018.
Merkelbach-Bruse2, R. Buettner1, M.A. Ihle1 Results: Of 1497 cases of NSCLC tested for therapeutic purposes in a 29-
1
University Hospital Cologne, Germany, 2 Institute of Pathology month period, 31 patients (2%) were identified with a MET exon 14
University Hospital of Cologne, Germany skipping mutation. In silico comparison with published data shows that
our amplicon based NGS assay can detect up to 96% of MET exon 14
Background & Objectives: Deregulation of histone deacetylases skipping mutations. In total, 46 cases of NSCLC with MET exon 14
(HDACs) plays an important role in tumourigenesis. Restoring a regular skipping were detected (including 4 non-therapeutic requests and 11 re-
acetylation profile by HDAC inhibitors (HDACi) is a promising thera- quests outside the 29-month period). This concerned 34 unique muta-
peutic approach. Human Rad Homolog B (HR23b), has been identified as tions, of which 26 were confirmed by RNA analysis. The histologically
a predictive biomarker and we showed previously that HDACi also ex- evaluable tumours in this cohort (n=30) had a varied morphology, with
hibit antiproliferative and pro-apoptotic effects in sarcomas depending on pleomorphic / sarcomatoid (n=12) as well solid-type adenocarcinoma
HR23b expression. We therefore aim to elucidate the regulatory relation- (n=9) comprising the majority, but also including non-mucinous lepid-
ship between HR23b expression and sensitivity towards HDACi as well ic-type adenocarcinoma / adenocarcinoma in-situ (n=7) and acinar (n=2)
as its effect on immunotherapy marker. patterns. Eleven patients with MET exon 14 skipping mutations received
Methods: A stable knockout of HR23b was generated in a malignant targeted therapy; they either participated in clinical trials or received
peripheral nerve sheath tumour (MPNST) cell line using CRISPR Crizotinib in compassionate use. We will present clinical responses for
/Cas9-technology. Proliferation and apoptosis was measured with the the 5 patients treated with Crizotinib.
ApoTox™Glo assay. Vorinostat was administered at IC50 concentration Conclusion: MET exon 14 skipping mutations can be reliably detected in
to wildtype and HR23bKO cells. Afterwards expression analysis of routine pathology tissue samples using DNA-based NGS analysis.
 Virchows Arch

Routine identification of MET exon 14 skipping mutations adds substan- The common nexus of the described cases is a long time between the
tially to personalised targeted treatment strategies for NSCLC patients. implant of the prosthesis and the development of squamous cell
carcinoma.
Methods: We present the case of a 51-year-old woman who in 1998
MD-05-005 developed a ductal carcinoma in the left breast with metastasis in 4 lymph
The diagnostic landscape and yield of predictive somatic molecular nodes. She was treated with surgery and tamoxifen for 10 years. In 2001,
analyses for stratification of cancer therapy in the Netherlands right prophylactic mastectomy was performed with retropectoral implant
E. Steeghs1, E.K. de Jong1, R.W. Willems1, Q.J. Voorham2, P.A. of physiological saline serum. Seventeen years later, presented in the right
Seegers2, K. Grünberg1, M.J. Ligtenberg1,3 breast, a prominent swelling with clinical inflammatory aspect, without
1
Department of Pathology, Radboud University Medical Center, fever.
Nijmegen, The Netherlands, 2 PALGA: The Nationwide Network and Results: Surgical intervention was performed with an introperative fro-
Registry of Histology and Cytopathology, Houten, The Netherlands, zen study that revealed infiltrating squamous cell carcinoma associated
3
Department of Human Genetics, Radboud University Medical Center, with the mammary periprosthetic capsule. The neoplasm appeared
Nijmegen, The Netherlands completely compoused by squamous cell cords moderately differentiated
with some keratin pearls and dyskeratosis. No glandular neoplastic com-
Background & Objectives: Unequal uptake of predictive analyses for ponent was identified. The periprosthetic capsule had transition from
cancer therapy, the rapid increase of molecular markers and targeted areas of synovial metaplasia to squamous metaplasia, dysplasia and in-
therapies, and detection of variants of unknown significance indicate vasive carcinoma.
the need for standardization and evaluation of predictive diagnostics. Conclusion: The few cases described do not allow us to recognize a
We studied molecular analyses (i.e. techniques, diagnostic yield) for gas- specific mechanism of oncogenesis, but the possibility of a prolonged
trointestinal stromal tumours (GIST), melanoma, colorectal carcinoma irritative process of a capsule that eventually developed metaplasia and
(CRC), and non-small cell lung cancer (NSCLC) in the Netherlands. squamous dysplasia seems a probable mechanism. It does not seem that
Methods: Pathology reports containing predictive analyses are collected factors of genetic susceptibility participate despite the previous associa-
from all 46 pathology departments via the Dutch Pathology Registry tion in our case of a contralateral ductal carcinoma
(PALGA) between October 2017 and June 2019.
Results: In the first year, predictive molecular analyses for GIST
(n=255), melanoma (n=1205), CRC (n=2325), and NSCLC (n=3355; PS-01-002
evaluation of 6 months) were performed in 14, 22, 22, and 21 pathology Reliability of HER2 immunohistochemistry in invasive breast carci-
departments, respectively. Targeted NGS was predominantly used (>80% nomas with micropapillary features
for GIST, CRC, NSCLC, and >60% for melanoma), but also N.E. Alkanat 1 , L. Atakishieva 2 , Z. Kadylbek 3 , A. Uner 1 , K.
MassARRAY and single gene analyses were performed. In total 31% of Kosemehmetoglu1
1
the analysed patients may benefit from targeted therapies, defined by Hacettepe University Faculty of Medicine, Department of Pathology,
alterations in KIT or PDGFRA for GIST (88%), BRAF for melanoma Turkey, 2 Kazan State Medical University, Russia, 3 Semey Medical
(45%), EGFR, BRAF, MET, ERBB2, ALK, or ROS1 (18%) for NSCLC, University, Kazakhstan
or absence of KRAS, NRAS, and BRAF mutations (36%) in CRC.
Moreover, variants associated with resistance, that give access to clinical Background & Objectives: Preceding studies on breast carcinomas with
trials, and variants of unknown significance were reported. micropapillary features have pointed a discordance between HER2 im-
Conclusion: We present an overview of the diagnostic landscape of munohistochemistry (IHC) and florescent in situ hybridization (FISH)
predictive molecular analyses in the Netherlands. Next, these results results. Accordingly, American Society of Clinical Oncology/College of
will be enriched with clinical characteristics to obtain insight into American Pathologists (ASCO/CAP) guidelines highlighted the impor-
the uptake of the molecular tests and their use in treatment deci- tance of tumour morphology in HER2 testing; 1+ HER2 IHC - “incom-
sions. plete and intense staining” - may be HER-2 amplified by FISH in certain
breast carcinoma subtypes. In this study, we aimed to identify HER2
This work is part of the research programme Personalised Medicine, status by IHC and FISH in invasive breast carcinomas with
financed by the Netherlands Organisation for Health Research and micropapillary features in our center.
Development (ZonMw, project number 846001001). Methods: Eighty-six carcinomas with micropapillary features diagnosed
between 2014-2018 were included in the study and HER2 IHC results
were recorded. 3-mm diameter tissue microarrays were constructed. 52/
Poster Sessions 86 cases were tested using FISH (HER2 FastProbe) according to the 2018
ASCO/CAP recommendations.
Results: HER2 gene was amplified in 10/52 (19%) of the cases: Regarding to
HER2 IHC, all of 3+ (n=7), 3 of 2+ (n=11) and none of 1+ (n=8) cases
Sunday, 8 September 2019, 09:30 - 10:30, Agora 3 revealed HER2 amplification. It was remarkable that immunohistochemically
PS-01 | Breast Pathology 0 and 1+ scored cases showed no HER2 amplification.
Conclusion: HER2 IHC and FISH results were found to be con-
PS-01-001 cordant and HER2 IHC is a highly reliable tool in assessment of
Breast implant-associated squamous cell carcinoma HER2 status in invasive breast carcinomas with micropapillary
L. Alfaro1, M.J. Roca1, A. Jimènez1, C. Vázquez2 features.
1
Pathology Hospital 9 de Octubre, Valencia, Spain, 2 Surgery. Hospital 9
de Octubre, Valencia, Spain
PS-01-003
Background & Objectives: Neoplasms associated with breast implants ASCO/CAP testing guidelines in breast cancer: impact of the up-
are very uncommon. Some cases of anaplasic lymphomas have been dated recommendations
described and, less frequently, there have been reported isolated cases X. Ara-Mancebo1, C. Alborch1, E. Fuentes-Camps1, S. Ramón y Cajal1,
of squamous cell carcinoma in the international literature with a total V. Peg-Camara1
1
amount of ten cases. Vall d'Hebron University Hospital, Spain
Virchows Arch

Background & Objectives: HER2 has become a pivotal marker in Methods: We studied human breast cancers from two cohorts (cohort I,
breast cancer, as patients with a tumour overexpressing this protein n=176; cohort II, n=192), and mRNA data from TCGA and two
can benefit from a targeted therapy. In 2018, the new ASCO/CAP METABRIC cohorts (n=2287). Stathmin protein expression was evalu-
guidelines for HER2 testing were issued, featuring two major up- ated on TMA slides by a semi-quantitative staining index (SI; high ex-
dates: the IHC 2+ (equivocal) definition, and the management of less pression: SI≥6). Proliferating microvessel density (pMVD) and vascular
frequent ISH groups. We aim to retrospectively evaluate how these proliferation index (VPI=pMVD/MVD) were used as novel angiogenesis
changes affect the HER2 prevalence comparing them with the former markers (cut-off upper quartile).
recommendations. Results: Genes differentially expressed between Stathmin high versus
Methods: We established two cohorts from our Institutional database: low tumours were significantly involved in cell proliferation (top-ranked
cases from January to May 2018, diagnosed based on 2013 upregulated genes), and genes reflecting ESR1 and ER–related signalling
ASCO/CAP guidelines (group A); and cases from June to September were down-regulated in Stathmin-high tumours. Gene sets related to im-
2018, diagnosed based on the modified criteria (group B). We conducted mune cell activation and VEGF signalling were enriched among
a retrospective review comparing the results of each group. Stathmin-high cases. Stathmin was associated with signature scores
Results: 584 patients were included, 317 in group A and 267 in group B. reflecting T-cell activation, as well as with higher expression of PD-1,
IHC results were as follows: IHC 0, 96 patients (30.3%) in group A vs. 95 PD-L1, CTLA4 and FOXP3 (P≤0.002). Further, Stathmin expression
(35.6%) in group B; IHC 1+, 121 (38.2%) vs. 113 (42.3%); IHC 2+, 61 correlated significantly with a 32-gene vascular proliferation score
(19.2%) vs. 33 (12.4%); IHC 3+, 39 (12.3%) vs. 26 (10.2%). ISH studies (Spearman's rho 0.20-0.30; P<0.001). High Stathmin protein expression
were performed in the IHC 2+ cases, with 6 (9.8%) amplified cases in was associated with increased pMVD (cohort I-II; P=0.005-0.047) and
group A vs. 3 (9.1%) in group B. high VPI (cohort II; P=0.007) in breast cancer tissues. Notably, Stathmin
Conclusion: IHC 2+ cases decreased applying the new guidelines, with a overexpression was significantly associated with high pMVD within the
consequent reduction in ISH tests. Besides, overall HER2 positive tu- triple negative subgroup (cohort I; p=0.010).
mours also decreased, but not significantly (p=0.287). Conclusion: Our findings indicate that high Stathmin expression iden-
tifies a subset of aggressive breast cancers characterised by ER negativity,
high proliferation, immune cell activation and vascular proliferation.
PS-01-004
TMA or whole slides to assess TILs in early-stage triple-negative The Research Council of Norway. The Helse Vest Research Fund.
breast cancer
A. Artemyeva1, D. Chuglova1, V. Kushnarev1, P. Krivorotko1, A.
Kudaybergenova1 PS-01-006
1
N.N. Petrov National Medical Research Center of Oncology, Russia Prognostic value of stromal CD10 expression in invasive breast
carcinoma
Background & Objectives: Triple-negative breast cancer is the group R. Ayadi1, D. Bacha2, O. Belkacem2, R. Yaiche2, A. Ben Amor3, S.
with the most unfavourable prognosis. TMA is a useful tool for any Gharbi2, S. Ben Slama2, A. Lahmar2, S. Bouraoui2
1
research but using TMA should be validated to study different population Pathology Department, Military Hospital, Tunis, Tunisia. University of
of lymphocytes. Tunis El Manar, Faculty of Medicine of Tunis, Tunisia, 2 Pathology
Methods: From 1235 cases of early breast cancer (T1-2, N0) triple- department, Mongi Slim Hospital, University Tunis El Manar,
negative was 132 cases. We studied TILs on H&E scanned slides in Medicine Faculty of Tunis, Tunisia, 3 Department of Gynaecology-
marked for TMA zones, using Salgado recommendations.Cases were Obstetrics, Mongi Slim Hospital, University Tunis El Manar, Medicine
assessed by experienced histopathologist. Faculty of Tunis, Tunisia
Results: Distributions of TILs in specific cores was following: the
first group (TILs in tumour stroma less than 10%) was the biggest Background & Objectives: Several studies have shown that CD10 ex-
and comprised 52 cases (44,1%), the second group (TILs in tumour pression in tumour stroma is associated with
stroma 20-40%) with 38 cases (32,2%), and in the third group we biological aggressiveness in many tumours, by promoting their growth
found the smallest number of cases (TILs more than 50%) with 28 and metastases. As regards breast carcinomas, the prognostic value of
cases (23,7%). stromal CD10 expression is still controversial with discordant results.
Conclusion: TMA spots should be created in order to specific aims. The aim of this study was to assess the prognostic value of stromal CD10
Otherwise they may not contain for example stroma at all or other specific expression in invasive breast carcinomas.
detail. However, using of two or more cores with tool diameter of 2 mm Methods: We retrospectively analysed the immunohistochemistry stro-
can be helpful for displaying heterogenity of tumour. mal CD10 expression in 57 patients with non-specific type invasive
(NST) carcinomas. Results were separated into three categories, based
on positive cell proportions with 10 and 30% thresholds. The relationship
PS-01-005 between CD10 expression and clinical, histopathological and evolutive
Stathmin expression is associated with immune cell responses and features were analysed by Chi2 and Fisher tests. Kaplan-Meier analysis
vascular proliferation in breast cancer was used to investigate CD10 prognostic value.
C. Askeland1,2, E. Wik1,2, I. Stefansson1,2, K. Krüger1, K. Collett1,2, G. Results: The average age in our series was 56.4 years. Positive stromal
Knutsvik1,2, J. Arnes2, T. Aas3, L.A. Akslen1,2 CD10 expression was noted in 28 patients (49%). CD10 staining signif-
1
Centre for Cancer Biomarkers CCBIO, Department of Clinical icantly reduced recurrence-free survival (p = 0.001), but had not influence
Medicine, Section for Pathology, University of Bergen, Norway, on overall survival.
2
Department of Pathology, Haukeland University Hospital, Bergen, The expression showcased correlation with tumour size> 2 cm, grade III,
Norway, Norway, 3 Department of Surgery, Haukeland University negative estrogen receptors, amplified HER2, phenotypic profiles
Hospital, Bergen, Norway "HER2", “triple negative" and " luminal A ", Ki67 index ≥15%, presence
of lymph node metastases, systemic metastases at diagnosis, and occur-
Background & Objectives: Stathmin, a microtubule destabilizing protein, is rence of local and systemic recurrences.
linked to cell proliferation and tumour aggressiveness. By using transcriptional Conclusion: Stromal CD10 expression in invasive NST breast carcino-
and protein data, we examined associations between Stathmin and stromal mas may be considered as prognostic factor, predictive of low recurrence-
responses such as immune cell presence and vascular proliferation. free survival and associated with high invasive and metastatic potential.
 Virchows Arch

PS-01-008 (n=248) and 3+ (n=1) by the 2018 scheme. 245 cases (11%), were con-
Agreement between immunohistochemically defined intrinsic sub- verted from 2+ to 1+. 3 cases (0.14%) doubtful classified as 3+/2+ before,
type estimation and Prosigna breast cancer prognostic gene signature changed to 2+ (FISH not amplified) and only 1 case was converted from a
assay in a clinical cohort at the Medical University of Vienna doubtful 2+/3+ to 3+ (0.04%), confirmed later by FISH. The cases clas-
Z. Bago-Horvath1, K. Tendl1, L. Monschein1, R. Exner2, F. Fitzal2, E. sified as 3+ (32%) and 0 (57%) by both guidelines, did not show signif-
Bergen3, M. Seifert4, C. Singer4, M. Rudas1, L. Müllauer1 icant changes.
1
Department of Pathology, Medical University of Vienna, Austria, Conclusion: 11.31% of all the cases were re-defined using the updated
2
Department of Surgery, Medical University of Vienna, Austria, 2018 ASCO/CAP guideline. Most of them had changed from 2+ to 1+
3
Department of Medicine I, Medical University of Vienna, Austria, (11%). Most of the doubtful cases classified as 3+ / 2+ with HER2 IHC
4
Department of Obstetrics and Gynaecology, Medical University of scores, were redefined as 2+, as well as many 2 + / 1+, that changed to 1+,
Vienna, Austria according the 2018 guideline. The new guideline is a helpful and better
comprehensive tool to assess the HER2 status designation.
Background & Objectives: The present study evaluated the correlation
of Prosigna breast cancer assay intrinsic subtype (IST) with immunohis-
tochemical (IHC) IST estimation in a clinical cohort. PS-01-010
Methods: 150 tumours from 146 women with immunohistochemical Heterogeneity of cancer-associated fibroblasts in invasive carcinoma
luminal tumours were analysed by Prosigna assay. ER, PR, HER2 and of no special type (IC NST)
Ki67 expression were accessed by IHC. Ki67 cutoff values of ≥20%, T. Bezuglova1, T. Bezuglova1, L.V. Kaktursky1, M. Mnikhovich1, A.
≥30% and ≥40% were investigated for discriminating Luminal (Lum) A Asaturova2, V. Kometova3, I. Vasin4, S. Snegur4, D. Kusch5, N.
from LumB tumours. In addition, the role of the cutoff value of Ki67 Malyugin5
≥20% and ≥30% in combination with PR receptor expression and histo- 1
Research Institute of Human Morphology, Russia, 2 FSBI 'National
pathological grading were evaluated, regarding clinical and genomic cor- Center for Obstetrics, Gynaecology and Perinatology named after V.I.
relation for defining subtypes. Statistical analyses were conducted using Kulakov' Ministry of Healthcare Russian Federation, Russia, 3 Federal
Cohen’s kappa coefficient. State Budget Institution National Medical Research Center of Obstetrics,
Results: Of 146 patients (median age 55.5 years), 60% were lymph node Gynaecology and Perinatology Ministry of Healthcare of the Russian
positive. 119 (79.3%) tumours were of LumB subtype by Prosigna and 78 Federation (Moscow), Russia, 4 Ryazan Reginal Clinical Hospital,
(52%) by IHC, respectively, using a Ki67 cutoff ≥20% for LumB disease. Russia, 5 Pirogov Russian National Research Medical University
A fair agreement between Prosigna and IHC IST (κ=0,326) was demon- (Moscow), Russia
strated. Using a Ki67 cutoff ≥30 % slightly improved agreement
(κ=0,411). Combining Ki67 with grade and low PR status did not im- Background & Objectives: Cancer-associated fibroblasts (CAF) are a
prove agreement substantially. key component of tumoural stroma and play an important role in tumour
Conclusion: Agreement between Prosigna luminal IST and IHC estimation progression. Tumour cells interact with their microenvironment, which
proves to be fair at best, independently of Ki67 cutoff values between 20%- includes CAF, immune cells, endothelial cells, pericytes, and components
40%. Multigenomic tests, such Prosigna, can provide independent informa- of extracellular matrix. All of them promote growth of tumour cells, have
tion for adjuvant therapy decision in cases where Ki67 IST estimation alone is immunosuppressive and angiogenic functions, induce epithelial–
not sufficient. These associations should be subjected to further investigation mesenchymal transition (EMT). Six types of CAF were described: asso-
to improve cost-effectivity regarding the utilisation of the assay. ciated with a-smooth muscle actin (a-SMA), podoplanin, hyaluronate,
fibroblast activation protein (FAP), protein S100A4, and platelet-
derived growth factor (PDGF) expression.
PS-01-009 Aim: To study heterogeneity of cancer-associated fibroblasts in IC NST.
Retrospective analysis of 2200 HER2 cases evaluated according to Methods: We studied 82 cases of IC NST, using light microscopy, im-
the 2013 ASCO/CAP guidelines and its correlation with the updated munohistochemical study with antibodies to cytokeratin AE1/AE3,
2018 guideline and its impact in HER2 status CK18, E-kadherin, vimentin, podoplanin, a-SMA, CD44 and study with
R.I. Bermudez Cameo1, H.P. Almanzar Comas1, B. Eizaguirre Zarza1, S. alcian blue (pH 2,5-2,7) and PAS-reaction.
Bakali Badesa1, J.I. Franco1, M.J. Viso Soriano1, A. Sobrino Prados1, A. Results: In IC NST we identified 3 types of CAF: associated with
Arellano Alvarez1, N. Estrada Mallarino1, C. Del Agua1, E. Gimeno CD44, a-SMA, podoplanin, and hyaluronate expression. Expression
Esteras1, V. Sanz Salvador1, V. Malo Nieves1 of all 4 markers was maximal in areas of invasive growth (areas of
1
Hospital Universitario Miguel Servet Zaragoza, Spain EMT) and was practically absent in central part of tumour parenchy-
ma. Expression of CD44 and hyaluronate in CAF attest to their be-
Background & Objectives: Human epidermal growth factor receptor 2 longing to mesenchymal stem cells. CAF were identified
(HER2, ERBB2) is a valuable prognostic and predictive biomarker in immunohistochemically in all cases of EMT therefore we can assume
breast cancer with an essential significance in selecting patients with that they stimulate EMT.
invasive breast cancer, for treatment with HER2-targeted therapy. Its as- Conclusion: Three types of CAF were identified in stroma of IC NST.
sessment is made by IHC and Fluorescence in situ hibridation (FISH). Connection between CAF and expression of CD44 by mesenchymal stem
Since the 2018 ASCO/CAP guideline release, we have notice much cells was defined. Maximal density of CAF was registered in areas of
clearer instructions and recommendations for HER2 status designation, invasive growth (areas of EMT). CAF play a role in stimulation of growth
and is our purpose to study the correlation between the 2013 and 2018 and invasion of tumour cells and maintenance of EMT.
ASCO/ CAP guidelines and its impact in HER2 status.
Methods: We retrospectively reviewed the results of the HER2- IHC tests
of 2200 cases of invasive breast cancer from our histopathology database, PS-01-011
between January 2014 and December 2018, that were evaluated with the Metastastic renal cell carcinoma of sarcomatoid type simulating gen-
2013 ASCO / CAP guideline and then re-evaluated with the updated eralised breast cancer; a case report and our experiences between
version of 2018 and confirmed by FISH. 2000 and 2018
Results: The analysis of the correlation between both guides, revealed a I. Björnheden1
1
change of status of HER2 IHC scores in a total of249cases. Among these University and Regional Laboratories Region Skåne, Department of
cases according to the 2013 guideline were re-defined as 1+ or 2+ Pathology, Malmö, Sweden
Virchows Arch

Background & Objectives: We present a case of an 83-year-old woman diagnosis, review of clinical history is essential: 75% of patients had a
with multiple subcutaneous lesions, bilateral nodules in breasts, intrathoracic history of known primary tumour.
and intrabdominal, and clinical suspicion of generalized breast cancer. A core These findings emphasize the need to accurately establish these tumours
needle biopsy was performed of a 3 cm deltoid subcutaneous mass, to con- as metastases, especially in high-grade triple negative tumours or cases
firm the diagnosis and guide choice therapy. Microscopy showed a pleomor- with positive hormone receptors. This may require complementary im-
phic spindle cell proliferation with large nuclei, coarse chromatin and multi- munohistochemical and molecular study to characterise the disease and
ple nucleoli, growing in loosely arranged netlike pattern, intermixed with avoid unnecessary therapeutic procedures.
necrosis and inflammation – not typical for usual breast cancers.
Methods: Extensive immunohistochemistry showed positivity only for pan-
cytokeratins, vimentin, focal for carbonic anhydrase IX and PAX8, leading to PS-01-014
the diagnosis of metastasis of sarcomatoid renal clear cell carinoma. The relationship between tumour-infiltrating lymphocytes, vascular
Radiology showed a 4 cm mass in the left kidney, resembling an atypical cyst. invasion and stromal elastosis in breast cancer
Between 2000 - 2018, 151 cases of metastasis of clear cell renal carinoma Y. Chen1, T.A. Klingen2, H. Aas2, E. Wik3,4, L.A. Akslen3,4
1
were diagnosed in the University hospitals in Malmö/Lund - only 15 with Oslo University Hospital, Norway, 2 Vestfold Hospital, Norway,
3
metastasis as a first manifestation, and not a single one of these with Centre for Cancer Biomarkers CCBIO, Department of Clinical
sarcomatoid features. Medicine, Section for Pathology, University of Bergen, Norway,
4
Results: This case report serves as an excellent example of what a tre- Department of Pathology, Haukeland University Hospital, Bergen,
mendous impact the pathological examination can have on the diagnosis Norway
and treatment of a patient, when there is a different clinical diagnosis
suspected. Furthermore, our statistic results underline the unique presen- Background & Objectives: The tumour stroma plays a critical role in
tation of this rare subtype of cancer, which makes it important for us to breast cancer progression. Here, we investigated associations between
share with our colleagues all over the world. subtypes of tumour-infiltrating lymphocytes (TILs), vascular invasion,
Conclusion: This case of metastatic renal clear cell carcinoma of macrophage content, tumour stromal elastosis and detection mode in
sarcomatoid type simulating generalized breast cancer is a rare entity, breast cancer.
but it can not be forgotten, and a thorough pathological examination is Methods: We performed a population-based retrospective study from
needed to arrive at the correct diagnosis. The Norwegian Breast Cancer Screening Program in Vestfold County
(2004-2009) including 200 screen-detected and 82 interval cancers. The
amount of TILs (CD3, CD4, CD8, CD45, FOXP3) and macrophages
PS-01-012 (CD163) was examined by immunohistochemistry on TMA-slides.
Breast metastases from non-mammary neoplasms. A study of 20 Vascular invasion (CD31, D2-40) and presence of elastosis (high/low)
cases were determined on regular slides.
J. Bosch Schips1, C. Fabregat2, A. Stradella2, L. Pèrez-Tapia3,4, A. Petit1, Results: High amount of all TIL subtypes were significantly associated
M.R. Taco1, E. Guerra1, I. Català1, R. Campos de Pablo1, G. Ippoliti1, X. with lymphatic vessel invasion, and high counts of several subtypes
Matias-Guiu1, M.T. Soler-Monsó1,4 (CD3, CD8, CD45, FOXP3) were associated with blood vessel invasion.
1
Department of Pathology, Bellvitge University Hospital/IDIBELL. Levels of TIL subtypes also associated with high tumour cell proliferation
L'Hospitalet de Llobregat, Spain, 2 Department of Clinical Oncology, (by Ki67; except CD4). Further, TIL subtypes associated with low stro-
Catalan Institute of Oncology. L'Hospitalet de Llobregat, Spain, mal elastosis (CD3, CD45, FOXP3), and interval detected tumours (CD3,
3
Department of Radiology, Bellvitge University Hospital/IDIBELL. CD8, FOXP3). All TIL subtypes associated with high macrophage con-
L'Hospitalet de Llobregat, Spain, 4 Breast Unit, Catalan Institute of tent. Finally, high levels of CD3, CD4 and FOXP3 were associated with
Oncology. L'Hospitalet de Llobregat, Spain reduced recurrence free survival in Luminal-A tumours (P<0.05).
Conclusion: Different TIL subtypes relate to stromal features like vascular
Background & Objectives: Metastases from non-mammary tumours in the invasion, macrophage content, presence of elastosis, as well as tumour cell
breast (MNMTB) are rare. Their accurate diagnosis is of utmost relevance in proliferation, and interval detected tumours. Our findings support a link be-
the staging and treatment of neoplastic disease. We aimed to study the prev- tween immune cells and vascular invasion in more aggressive breast cancer.
alence and the neoplastic lineages that may define this form of presentation. Also, some TILs were prognostic within the Luminal A category.
Methods: We reviewed cases of MNMTB diagnosed in our center be-
tween 2009 and 2019. Hematological malignancies were ruled out.
Clinico-pathological data were assessed. PS-01-015
Results: Twenty cases were selected, of which 17 were women (85%) and 3 TILs in early-stage triple-negative breast cancer
men (15%), with a median age of 55 years (range 21-89). Diagnoses were A. Artemyeva1, D. Chuglova1, V. Kushnarev1, R. Paltuev1, N. Demina2,
performed by core needle biopsy only (CNB) in 13 cases (65%), fine needle A. Kudaybergenova1
1
aspiration only (FNA) in 5 cases (25%) and by CNB + FNA in 2 cases (10%). N.N. Petrov National Medical Research Center of Oncology, Russia,
2
Fifteen cases (75%) were metastatic carcinoma, 4 (20%) melanoma, and 1 Saint Petersburg State Paediatric Medical University, Russia
(5%) sarcoma. The most prevalent origin of MNMTBs for carcinoma was
lung (5 cases - 25%), followed by ovary (4 cases – 20%) and kidney (2 Background & Objectives: The group of triple-negative breast cancer
cases - 10%). There was also 1 case (5%) of: Merkel cell carcinoma of the has worse prognosis therefore it conciders as perspective field for study.
skin, atypical mediastinal carcinoid, cervical adenocarcinoma and oro- Methods: We studied TILs by direct microscopy HE slides using Salgado
pharyngeal basaloid carcinoma. The MNMTB of sarcoma was from an recommendations. From 1235 cases of early breast cancer (T1-2, N0)
embryonal gluteal rhabdomyosarcoma. triple-negative breast cancer (TNBC) was only 132 cases (9,35%).
Five patients (25%) debuted synchronously (primary disease and Results: Distributions of TILs was following: the first group (TILs less than
MNMTB), while 15 patients (75%) already had a known primary tumour. 10%) was the largest and comprised 53 cases (44,9%); the second group
The median interval between disease diagnosis and MNMTB was 38 (TILs 20-40%) – 35 cases (29,7%); the third group – 30 cases (25,4%).
months. With a mean follow-up of 11 months (range 1-65), 14 patients Conclusion: Breast cancer for a long time considered as tumour with low
(70%) have died and 6 patients (30%) are still alive with disease. immunogenicity. In our study we found that only one quarter of cases
Conclusion: In our series, the most prevalent metastases were those of TNBC has marked infiltration TILs. It compises 2,43% from cohort of
lung cancer, followed by ovarian cancer and melanoma. To perform early-stage breast cancer.
 Virchows Arch

PS-01-016 distributed c fine chromatin (91,3%), linear or cord like arrangement

Changes in mammary myoepithelial biomarker expression associate (60,8%), intranuclear inclusions (26%), smooth regular nuclear mem-
with luminal epithelial proliferation and progression to invasive brane (93,47%) and signet ring shape (19,5%).
disease Loss of E-Cadherin was found in all cases.
V. Deckwirth1, K. Rajakylä1, S. Cattavarayane1, P. Björkenheim2, O. ER was expressed in 95,6% and PR in 91,3% of all tumours. The majority
Vapaavuori2, A. Sukura1, S. Tojkander1 of cases (95,6%) showed negative expression of C-erbB2 oncoprotein.
1
Section of Veterinary Pathology / Faculty of Veterinary Medicine / Conclusion: It is important to identify the lobular type of breast carcino-
University of Helsinki, Finland, 2 Small Animal Hospital / Faculty of mas since it has different clinical, radiological and cytomorphological
Veterinary Medicine / University of Helsinki, Finland features as well as different course and therapeutic management. Better
knowledge of the key cytologic features of lobular carcinoma and variant
Background & Objectives: Mammary myoepithelial cells (MEC) are types can reduce diagnostic failure.
important for organostructural homeostasis. Their absence determines
stromal invasion. Several biomarkers characterise MECs in normal mam-
mary. Their gradual loss is suggested to concur with malignant transfor- PS-01-019
mation of luminal epithelial cells, with subsequent break-down of the A 5-year study concerning multiple breast cancer heterogeneity
MEC barrier. However, molecular mechanisms behind this barrier func- A. Dumitru1, T. Georgescu1, O. Voinea1, A. Evsei2, A. Birceanu-
tion are poorly understood. We investigated the association of basal/MEC Corobea3, M. Sajin4,5
1
cytoskeletal biomarkers, including alpha-smooth-muscle-actin (α-SMA), Department of Pathology, "Carol Davila" University of Medicine and
cytokeratin-5 (CK5) and cytokeratin-14 (CK14) to various non-invasive Pharmacy, Bucharest, Romania, 2 CESITO Center, Saint Mary Clinical
luminal epithelial proliferations, and the role of these proteins in the Hospital, Bucharest, Romania, 3 „Sfanta Maria" Clinical Hospital,
homeostasis of normal MEC layer. Bucharest, Romania, 4 SUUB, Romania, 5 UMF Carol Davila, Romania
Methods: Myoepithelial cellular optical density was determined of normal,
usual and atypical hyperplasia as well as ductal carcinoma in-situ structures Background & Objectives: At first, intra and intertumoural heterogene-
from scanned immunohistochemical whole slide images of comparative ca- ity may be daunting. Multiple breast tumours are the ideal prototype for
nine mammary model patients. Human mammary cell lines, depleted by the study of tumour heterogeneity. The analysis of these lesions was
siRNA or Lentiviral-based RNA interference for CK5, CK14 and α-SMA, performed in order to determine the impact that histopathological and
were utilized for screening biomarkers α-SMA, calponin, vimentin, dsg3, E- immunohistochemical heterogeneity might have in terms of classification
cadherin, P-cadherin, SLUG and cytokeratins in immunofluorescence or the possible reassessment in order to change the therapeutic manage-
stainings and Western blot experiments. ment. Even more, multifocality is not included among the prognostic
Results: We found that biomarker expression associated with ductal seg- factors in international guidelines on breast cancer, hence the usefulness
ment, cellular proliferation and malignancy. Furthermore, CK5, CK14 of this study.
and α-SMA were essential for maintaining normal mammospheroid Methods: We selected 37 cases of multiple mammary cancers diagnosed
structures. Additionally, CK5, but not CK14, determined maturation of over a 5-year period that did not benefit from neoadjuvant treatment,
contractile MEC layer as indicated by loss of α-SMA, calponin, vimentin, knowing that it may alter the expression of some immunomarkers and
SLUG, dsg3 and P-cadherin expression in CK5-deficient cells. even the tumour histology. Immunohistochemical characterization has
Conclusion: MEC cytoskeletal markers are lost along neoplastic progres- demonstrated the presence of expression heterogeneity with some tu-
sion. Of these, CK5 is crucial for full maturation of the mammary mours being reclassified. This has, at least virtually, a therapeutic impact.
myoepithelial layer and its loss causes differentiation bias towards lumi- Moreover, immunohistochemical evaluation of metastases has shown that
nal cell type and loss of myoepithelial barrier function. there are immunohistochemical mismatches at this level between primary
tumours, secondary ones and their metastases.
Supported by Academy of Finland Jane and Aatos Erkko Foundation Results: We proposed an algorithm for tumoural "dominance" in terms of
University of Helsinki PhD-student grant Finnish Foundation of aggressiveness based on morphological combined criteria (size,
Veterinary Research Finnish Veterinary Foundation. histotype), but also included immunohistochemical criteria using 4
markers. In 6 cases of multiple breast tumours, the dominant tumour
was not the index tumour (the largest tumour focus on which staging
PS-01-018 and acillary test are usually performed). Immunohistochemical heteroge-
Cytomorphologic features and immunocytological findings that sup- neity was also documented in 11 cases. Theoretically, this method appears
port the diagnosis of lobular breast cancer to be a timely one, but difficult to apply in the current practice.
S. Divani1, A. Vardouli1, G. Kalodimos1, P. Skoufogiannis1, A. Fericean1, Conclusion: According to the results, the current staging system of multiple
A. Staikou2, A. Dinou2 breast tumours is far from being a gold standard and does not really mirror the
1
Volos General Hospital Greece, 2 Technician, Greece complex behaviour of these tumours. In this case, the pTNM system should
incorporate a scoring system based on immunohistochemical criteria with
Background & Objectives: Lobular breast presents a wide spectrum of predictive and prognostic value to select the most aggressive tumour foci.
differences from tumours of ductal phenotype.
The aim of this study was to identify and analyse the cytologic features
and immunocytological findings that support the diagnosis of lobular PS-01-020
breast cancer. Influence of cold ischemia time to morphological and immunohisto-
Methods: We retrospectively reviewed 352 malignant breast cases and chemical features in breast carcinoma
we retrieved and analysed a series of 46 (13,06%) fine needle aspirates H. Faistova1, P. Kašparová1, A. Ryska1
1
with the diagnosis of invasive lobular carcinoma confirmed histological- The Fingerland Department of Pathology, University Hospital, Faculty
ly. The majority of patients 84,7% were postmenopausal. of Medicine Hradec Kralove Charles University Prague, Czech Republic
Immunocytochemistry for Estrogen, Progesteron receptors, E-Cadherin
and the oncoprotein C-erbB2 was performed in all cases. The various Background & Objectives: The influence of preanalytical procedures is
findings were classified. essential for evaluation of morphology, grade and receptor expression in
Results: Malignant cells showed: discohesive architecture (95,6%), little breast cancer. The cold ischemia time (CIT) between operation and im-
or no nuclear atypia (91,3%), low mitotic rate (97,8%), homogeneously mersion in formaldehyde is one of the critical steps of preanalytic phase,
Virchows Arch

but it is frequently not monitored. In our study, we focused on role of CIT PS-01-024
in breast resection specimens and on the possibility of its improvement. VENTANA HER2 dual ISH DNA cocktail assay; a HER2/Chr17
Methods: A cohort of 23 paired specimens from core-cut biopsy dual ISH automated assay with improved signals and higher first
(CCB) and resection of tumour (RES) was collected, CIT was re- pass rate
corded for each RES. Expression of estrogen and progesterone re- G. Harlow1, S. Mansor2, S. Lax3, P.R. Zollars4, J. Bentz5, A. Hanlon
ceptors and Ki67 were revised both for CCB and RES. The differ- Newell1, E. Walker1, J. Su1, R. Gniewek1, D. Eng1, R. Alam1, A. Babic1
1
ence between value of each variable in CCB and RES was calculat- Roche/Ventana Medical Systems Inc., USA, 2 KK Women's and
ed. For evaluation of morphology in RES, nuclear features, cellular Children's Hospital, Singapore, 3 GrazWest Institute for Pathology,
outlines, retraction artifacts and mitoses were evaluated indepen- Graz, Austria, 4 Clin-Path Associates PLC, USA, 5 Aurora Diagnostics,
dently by two observers on scale 0-3 and combined score (0-24) USA
was calculated.
Results: The differences in morphology, ER, PR, Ki67 between Background & Objectives: Human epidermal growth factor receptor
CCB and RES were correlated with CIT. The differences between 2 (HER2) plays a central role as a prognostic and predictive marker
RES and CCB ranged for ER from -70% to +10% (mean=7%, me- in breast cancer specimens. A reliable HER2 diagnostic test is cen-
dian=0), for PR -60% to +20% (mean=8.4%, median=-5%) and for tral to determining the eligibility of patients with breast cancer to
Ki67 -25% to +12% (mean=1.7%, median=0%), respectively. The targeted anti-HER2 therapies. Assessment of HER2 gene amplifica-
morphology-score in RES ranged from 13 to 20 (mean=18.3, medi- tion status by in situ hybridization (ISH) is a widely accepted diag-
an=20). CIT varied in 27-4258 min (mean=630,65, median=135). nostic test method. Multiple improvements have been made to the
There was no correlation of differences in individual variables and INFORM HER2 Dual ISH DNA Probe Cocktail Assay which has
CIT values. resulted in an increase in the first pass rate and a decrease in the
Conclusion: Even in cases with CIT longer than 3 days all markers assay run time.
were well evaluable. The extended CIT has not such strong influence Methods: We developed an improved oligonucleotide HER2/CHR17
on morphological and immunohistochemical features in our group of dual ISH assay (VENTANA HER2 Dual ISH DNA Cocktail Assay)
highly ER positive carcinomas as we expected. The possible expla- utilizing novel HER2 oligo probes labelled during synthesis with
nation is relatively low sensitivity of nuclear markers ER, PR and dinitrophenyl (DNP) and novel oligonucleotide probes labelled
Ki67 to CIT. post-synthetically with digoxigenin which are specific to the chromo-
some 17 centromere. Improvements to the INFORM staining proce-
Supported by European Regional Development Fund-Project BBMRI- dure and the detection chemistry were also made. To evaluate the
CZ: Biobank network – a versatile platform for the research of the first-pass-rate of the two Dual ISH assays five study sites each iden-
etiopathogenesis of diseases, No: EF16 013/0001674. PROGRES Q40/ tified, retrieved, and stained 135 retrospective FFPE invasive breast
11. carcinoma cases using both the INFORM assay and the VENTANA
assay. First pass rates were determined for each assay by running
them in parallel in a “real-world” clinical setting. Twenty nuclei
PS-01-023 (each containing red (Red ISH) and black (SISH) signals) were enu-
Adenoid cystic carcinoma of the breast: a retrospective analysis of a merated. If the HER2/Chr17 ratio fell between 1.8 to 2.2 (inclusive),
rare entity an additional 20 nuclei were enumerated. A new ratio was formed on
G. Gupta1, R. Ramakrishnan2 the basis of all 40 nuclei.
1
Imperial College Healthcare NHS Trust, United Kingdom, 2 North West Results: VENTANA Dual ISH run times vs INFORM run times were
London Pathology, United Kingdom reduced by 40%, 28%, and 31% on the VENTANA BenchMark ULTRA,
XT, and GX respectively. The average assay first pass rate for the Ventana
Background & Objectives: Adenoid cystic carcinoma (ACC) is an un- Dual ISH assay was 96%, the average INFORM assay first pass rate was
common breast malignancy, with 0.1% to 1% incidence. Our study aims 70%.
to a) determine radio-logical & pathological characteristics of this tumour Conclusion: The VENTANA HER2/CHR17 Oligo Probe ISH assay is a
& b) evaluate prognosis/outcomes of surgical intervention in a tertiary technological advance in cancer diagnostics that holds promise for im-
care hospital. proved laboratory efficiency and better staining quality.
Methods: A retrospective analysis of all ACC of breast at Charing Cross
hospital over the past 15 years was carried out.
Results: Of 6865 breast cancers, 11 ACCs were identified accounting for PS-01-027
0.16%. Median age was 59 years. Radiology ranged from complex cysts Clinicopathologic charateristics of HER2-positive mucinous carcino-
to asymmetrical dense radiopaque foci with micro-calcifications. 3 pa- ma of the breast
tients underwent mastectomy, one patient received adjuvant radiotherapy. Y. Jang1, E.Y. Cho1, S.Y. Cho1
1
8 patients had breast conservation surgery (BCS). 1 referred case had no Department of Pathology and Translational Genomics, Samsung
follow up data. Medical Center, Republic of Korea
Median tumour size was 23mm with predominant cribriform (8/10) &
occasional solid patterns (2/10). No perineural invasion was noted. All Background & Objectives: Mucinous carcinoma (MC) is a rare type of
tumours were triple negative. breast cancer, estimated to be 2% of invasive breast cancer. MC is typi-
7/10 cases underwent sentinel node biopsy (SNB) & none showed cally positive for estrogen receptor (ER), progesterone receptor (PR), and
metastasis. negative for HER2. However, HER2-positive MC rarely does occur.
Median disease free survival was 40.5 months. There was 1 recurrence & Clinicopathologic characteristics of HER2-positive MC have not been
2 distant metastases to brain, adrenals, lung & liver. Two out of these 3 investigated well.
showed high grade features. Methods: We experienced 24 HER2-positive pure MC among 591 pure
Conclusion:Breast-ACC is a rare triple negative tumour, best managed by MC (4.1%) from 1999 to June 2018. Medical records and pathology
BCS alone. Large tumours may occasionally need mastectomy with/without reports of all patients were obtained from electronic medical records.
radiotherapy. Although indolent, recurrence & metastasis are not uncommon Microscopic findings, including nuclear and histologic grade, type A/B,
with high grade tumours & tend to portend poor prognosis. These findings presence of extensive intraductal component (EIC), arrangement of tu-
reinforce the importance of tailored treatments & adequate follow-up. mour cells, were reviewed.
 Virchows Arch

Results: The mean age was 46. Five patients received neoadjuvant che- <1% of invasive breast carcinomas. Almost all of these neoplasms, in-
motherapy. The average tumour size was 2.7 (range 0.1 ~ 13) and T stage cluding only one previously-described case with basal marker expres-
was as follows; pT1mi: 1, pT1: 10, pT2: 4, pT3: 1, pT4: 1. Lymph node sions in a small cell carcinoma, are reactive for the estrogen receptor
metastasis was present in 7 cases. When compared to HER2-negative (ER) and/or the progesterone receptor (PgR). Herein, we present the first
MC, HER2-positive MC presented with more advanced T stage case, to our knowledge, of an invasive mammary carcinoma showing NE
(p<0.01), more frequent lymph node metastasis (p<0.01), and higher differentiation (ref. large cell neuroendocrine carcinoma, LCNEC) with
nuclear and histologic grade (p<0.05). Microscopically, there were 12 triple-negative, basal-like profiles.
type A, 6 type B, 4 mixed type A and B among HER2-positive pure Methods: A 53-year-old postmenopausal Japanese woman had a
MC. EIC was present in 9 cases. Micropapillary component and signet mass in the outer portion of her right breast detected by ultrasound
ring cells were present in 6 and 14 cases, respectively. During follow up, examination. Her familial history included one uncle with a pharyn-
distant metastasis developed in 3 patients. geal carcinoma and another diagnosed with gastric carcinoma.
Conclusion: Our results suggest that HER2-positive MC is a more ag- Ultrasonography revealed an irregularly-shaped, focally ill-defined,
gressive subgroup of MC. Biologic heterogeneity of MC should be con- hypo-echoic tumour as well as enlarged regional nodes. No other
sidered for adequate management. suspected lesions were revealed by either systemic CT or bone
scintigraphy.
An irregularly-shaped, grey-whitish tumour, which measured 10x8 mm,
PS-01-028 was noted in the specimen obtained at breast removal.
Residual pure lymphovascular invasion after neoadjuvant chemo- Results: Histologically, the invasive tumour consisted of medullary
therapy - a single Institution experience growth of large carcinoma cells with well-developed vascular stroma
Y. Jang1, E.Y. Cho1, S.Y. Cho1 and marked lymphocytic infiltration. Carcinoma cells had ovoid or
1
Department of Pathology and Translational Genomics, Samsung irregularly-shaped nuclei with granular chromatins and distinct nu-
Medical Center, Republic of Korea cleoli. Mitotic figures were numerous (108/10 hpf). Macrometastases
were identified in 5 of 8 regional lymphoglandula.
Background & Objectives: Pathologic complete response (pCR) is Immunohistochemically, the carcinoma cells were reactive for
defined as absence of invasive carcinoma in the breast after neoad- synaptophysin, CD56, cytokeratin 5/6, cytokeratin 14 and c-kit, and
juvant chemotherapy (NAC). Rarely, only lymphovascular invasion negative for chromogranin, ER, PgR (Allred’s scores: 0/0), HER1
(LVI) remains after NAC. There are few studies describing dismal and HER2. The MIB-1 index was 75.2%.
prognosis of these occasions. It is yet uncertain how to classify these Conclusion: Although, in the breast oncology field, the outcomes of
LVI only cases. NEC, mostly expressing ER and/or PgR, remain controversial, our
Methods: We have searched pathology files that contained ‘no residual current case with a primitive NE neoplasm with LC and basal cell-
tumour’ and ‘LVI’ from 2006 to 2013. Cases with residual ductal carci- like features, despite relatively small invasive lesions (pT1b) with
noma in situ (DCIS) were included. We reviewed electronic medical tumour-infiltrating lymphocytes, had multiple lymphogenous metas-
records, and microscopic slides. tases (pN2), with extra-nodal invasion. (Pathology International, in
Results:13 cases with LVI only cases after NAC were retrieved. All press)
patients presented with lymph node metastasis clinically.
Immunohistochemical phenotypes of initial biopsy were as follows; Grants-in-Aid for Scientific Research (16K08654 & 16H00668) from
ER+/HER2+: 3, ER+/HER2-: 1, HER2+: 4, ER-/HER2-: 5. After the Japanese Ministry of Education, Culture, Sports, Science and
NAC, DCIS remained in 8 cases. 9 cases showed residual tumour in the Technology and National Hospital Organization (NHO) Grant
lymph node (ypN0(i+): 2, ypN1mi: 2, N1: 3, N2: 1, N3: 1). 1 of 4 ypN0 (H29-NHO-01).
patients developed local recurrence and contralateral axillary metastasis,
and two of 9 patients with residual nodal disease (1 ypN1, 1 ypN2)
developed distant metastasis (one of these two patients died). When we PS-01-031
classified cases according to the extent of LVI (1+, 2+, 3+), recurrence High-molecular-weight insulin-like growth factor 2 secreting phyl-
occurred only in the LVI 3+ group. lodes tumour of the breast presenting as a hypoglycemic attack
Conclusion: Our results showed much better prognosis of LVI only cases T. Kawasaki1,2, S. Ueda1, Y. Ichinose1, E. Hirokawa1, H. Shimada1, I.
than previous studies. However, classifying LVI only cases as pCR would Sugitani1, H. Sano1, T. Hasebe1, T. Takahashi1, A. Osaki1, T. Saeki1, Y.
be inappropriate. Recurrence was not associated with residual nodal dis- Oikawa3 , I. Inoue 3, M. Noda3, A. Shimada3 , Y. Nagashima4, K.
ease. Extent of LVI may have some relation to the patient outcome. Kamada1, S. Kanno1, M. Urano5, M. Kuroda5, T. Utsumi5, T. Hayashi5
1
Saitama Medical University International Medical Center, Japan,
2
National Hospital Organization Nagoya Medical Center, Japan,
3
PS-01-030 Saitama Medical University, Japan, 4 Tokyo Women's Medical
Invasive carcinoma with neuroendocrine differentiation of the breast University, Japan, 5 Fujita Health University, Japan
showing triple negative, large and basal cell-like features
T. Kawasaki1,2, N. Teramoto3, Y. Hoshida4, Y. Murata5, K. Sugiyama2, Background & Objectives: Non-islet cell tumour hypoglycemia
M. Oiwa6, C. Muramatsu7, J. Ichikawa8, I. Sugitani1, S. Ueda1, T. (NICTH), among the significant causes of fasting hypoglycemia, has
Hasebe1, A. Osaki1, K. Kaira1 mainly been reported in solitary fibrous tumour, hepatocellular carcinoma
1
Saitama Medical University International Medical Center, Japan, and mesothelioma patients.
2
National Hospital Organization Nagoya Medical Center, Japan, Methods: A 42-year-old premenopausal Japanese woman, who had
3
National Hospital Organization Shikoku Cancer Center, Japan, had a palpable mass of the left breast for several months, was found
4
National Hospital Organization Osaka Minami Medical Center, Japan, unconscious at home by a family member early in the morning. She
5
National Hospital Organization Tokyo Medical Center, Japan, 6 Nagoya was emergently transported to our hospital. Clinical examination
Medical Center, Japan, 7 Shiga University, Japan, 8 University of revealed a mass of approximately 15 cm in the entire left breast,
Yamanashi, Japan with a circulatory skin disorder. The blood sugar level was 33 mg/
dL, resulting in hypoglycemia, and a 50% glucose liquid injection
Background & Objectives: The WHO classifies mammary carcinomas immediately improved her awareness level. Thoracoabdominal com-
with neuroendocrine (NE) features as a special tumour entity representing puted tomography demonstrated a huge, lobulated left breast tumour
Virchows Arch

showing heterogeneous internal echoes without enlargement of the Conclusion: We found that cases with high content of cancer stem cells are
lymph nodes (axillary, supraclavicular, cervical, and mediastinum) more regulated by signalling pathways NOTCH and WNT. Expression of
or distant metastasis. We performed a vacuum-assisted core biopsy NF-Kb and PI3K signalling molecules (which are responsible for activation
of the breast lesion, and the histologic diagnosis was a phyllodes of eponymous signalling pathways) appeared in all cases, while expression of
tumour. PTEN phosphatase, which inhibits PI3K signalling pathway, was more com-
Results: The cut surface of the mastectomy specimen contained a mon for cases with low content of cancer stem cells. Signalling pathway
relatively well-defined solid tumour, measuring 170x148x118 mm, Hedgehog was activated only in AlDH1A1-negative breast cancer.
partly with a typical phyllodes pattern. Histologically, this lesion was
composed of proliferation of both epithelial and stromal components
(i.e. fibroepithelial tumour). A focally permeative tumour border, PS-01-033
moderate stromal cellularity with mild to moderate stromal atypia, Pathological predictors of axillary node involvement in breast cancer
and very focal stromal overgrowth were observed. Mitotic figures of patients
the stromal cells were seen in six of 10 high-power fields. There were Y. Dergunova 1 , V. Kometova 2 , V. Bojenko 2 , M. Dardyk 2 , M.
no malignant heterologous elements. Immunohistochemical exami- Rodionova2, V. Rodionov2
1
nations revealed the neoplastic cells to be diffusely positive for Ulyanovs Regional Clinical Oncological Center, Russia, 2 National
insulin-like growth factor (IGF)-2, while being negative for insulin Medical Research Center of Obstetrics, Gynaecology and Perinatology
and STAT6. The Ki67 (MIB-1) labelling index of the mesenchymal named after acamician V.I.Kulakov, Russia
cells was 13.7%. Furthermore, Western blot analysis demonstrated
large amounts of high-molecular-weight IGF-2 in the resected tu- Background & Objectives: The purpose of the study was to determine
mour tissue. Based on these pathological as well as biochemical the predictors of regional lymph node involvement in breast cancer pa-
findings, NICTH due to a borderline phyllodes tumour of the breast tients on the basis of biological characteristics of the primary tumour.
was identified. Postoperatively, her hypoglycemia immediately dis- Methods: The retrospective study included 200 patients with verified
appeared, and her blood glucose level stabilized near 120 mg/dL. unicentric invasive breast cancer T1-4N0-3M0 treated from 2012 to 2015.
Conclusion: The possibility of NICTH should be kept in mind when exam- The patients were divided into 2 groups:100 patients with lymph nodes
ining a patient experiencing a hypoglycemic episode. Furthermore, although metastases (N+) and 100 patients without metastases (N-).
exceptionally rare, this unusual condition can occur with a mammary mass. Results: Tumour size (p=0,027), histological type (p‹0,001), grade
(p=0,027), Integrated Pathological Index (IPI) (p‹0,001), lymphovascular
Grants-in-Aid for Scientific Research (16K08654 & 16H00668) from invasion (p‹0,001) and HER2-status (p=0,0002) were the most powerful
the Japanese Ministry of Education, Culture, Sports, Science and predictors of axillary lymph node involvement. There was no statistically
Technology and National Hospital Organization (NHO) Grant significant correlation between ER-status (p=0,092), PgR-status
(H29-NHO-01). (p=0,081), Ki-67 (p=0,132), molecular subtypes (p=0,213) and axillary
lymph node metastases. Multivariate logistic regression for significant
variables was used to create a nomogram.
PS-01-032 Conclusion: Size of the primary tumour, histological type, grade, IPI,
Expression of NF-kB, PI3K, WNT, Hedgehog and Notch in HER-2 lymphovascular invasion and HER2-status are independent prognostic
positive breast cancer with low and high content of cancer stem cells factors of axillary lymph node involvement and can be used by clinicians
A. Brilliant1, Y. Brilliant1,2, N. Kazantseva3, S. Sazonov2 to plan axillary surgery volume in breast cancer patients.
1
Institute of Medical Cell Technologies, Russia, 2 Ural State Medical
University, Russia, 3 Sverdlovsk Regional Oncological Center, Russia This work was sponsored by grant from the National Natural Science
Foundation of Russia (АААА-А18-118053190016-7).
Background & Objectives: We investigated the expression of the NF-
kB, PI3K signalling pathways, as well as WNT, Hedgehog, NOTCH in
cells of ALDH1A-positive and -negative cases of HER-2 positive breast PS-01-034
cancer Changes of oestrogen receptor, progesterone receptor and Her2/neu
Methods: The material of 110 cases was explored. To determine the statuses of local metastases compared with primary tumour in breast
presence of stem cells in tumour population, the expression of cancer
ALDH1A1 in cancer cells was investigated. Expression of ER, PR, K. Konyshev1, S. Sazonov1
1
HER-2 and Ki-67 was studied by immunohistochemical method to iden- Institute of Medical Cell Technologies, Ural State Medical University,
tify cases of HER-2 positive breast cancer. The expression of signalling Russia
molecules PI3K, NF-kB, WNT, Notch, Hedgehog was explored by
innunohistochemical method. Background & Objectives: Discordance of estrogen receptor (ER), pro-
Results: All cases were investigated for ALDH1A1 expression and were gesterone receptor (PR) and Her2/neu status of primary and metastatic
divided into two groups - with low (expression of ALDH1A1 was esti- breast cancer is the possible reason of therapy failure. Objective: to eval-
mated as 0, 1+) and high (expression of ALDH1A1 was estimated as 2+, uate discordance of ER, PR and Her2/neu statuses of breast cancer pri-
3+) content of cancer stem cells. mary tumour and local metastases.
We found that 20% of cases of HER-2 positive breast cancer were posi- Methods: Samples of primary tumour and local metastasis obtained from
tive for ALDH1A1. 104 patients were stained immunohistochemically with antibodies to ER,
Expression of explored signalling molecules in studied cases is shown in PR (1D5, Pgr-636, Dako) and Her2/neu (4B5, Ventana). Silver-enhanced
the table. in situ hybridization (Ventana) was used when needed. Allred score and
ASCO/CAP 2013 guideline were applied to define positive or negative
tumour status. Frequencies of each biomarker positive to negative and
NF-kB PI3K PTEN NOTCH WNT HH negative to positive status change were compared using Fisher’s exact
probability test.
high ALDH1A1 100% 100% 9% 36% 36% 0% Results: We observed the following biomarker status changes in metas-
low ALDH1A1 100% 100% 11% 30% 27% 7% tases compared with primary tumour. ER: totally – 10 cases out of 104
(9,6%, 95% CI 5,0-17,4%), positive to negative – 5 cases out of 73 (6,8%,
 Virchows Arch

95% CI 2,5-15,9%), negative to positive – 5 cases out of 31 (16,1%, 95% Centre, Skaraborg Hospital, Skövde, Sweden, 4 Dept of Surgery,
CI 6,1-34,5%) (p=0,16). PR respectively: 17 out of 104 (16,3%, 95% CI Sahlgrenska University Hospital, Institute of Clinical Sciences,
10,1-25,2%), 7 out of 58 (12,1%, 95% CI 5,4-23,9%), 10 out of 46 Sahlgrenska Academy at University of Gothenburg, Sweden
(21,7%, 95% CI 11,4-36,8%) (p=0,28). Her2/neu respectively: 9 out of
104 (8,6%, 95% CI 4,3-16,2%), 5 out of 16 (31,2%, 95% CI 12,1-58,5%), Background & Objectives: There is an increasing demand to provide
4 out of 88 (4,6%, 95% CI 1,5-11,9%) (p=0,004). reliable biomarker status for breast cancer patients, but with shorter turn-
Conclusion: ER, PR and Her2/neu statuses switched in 9,6%, 16,3% and around times than traditional immunohistochemistry (IHC). Xpert®
8,6% of cases in metastatic lesion compared with primary breast cancer Breast Cancer STRAT4 is a standardised RT-qPCR-based platform that
tumour. Her2/neu-status more frequently changes from positive to nega- quantitates ESR1, PGR, ERBB2, MKi67 mRNA expression in formalin-
tive then from negative to positive. fixed, paraffin-embedded (FFPE) tissues in less than two hours. The aim
of this retrospective study was to evaluate the concordance between IHC
Supported by Ural State Medical University state assignment № 056- and the automated STRAT4 diagnostic platform.
00151-18-00. Methods: The concordance between standard of care IHC/SISH and
STRAT4 was performed using FFPE sections from 100 invasive breast
carcinomas (core biopsy and matching surgical specimens) that were
PS-01-035 retrospectively evaluated for ESR1, PGR, ERBB2 and Mki67.
Breast implant associated anaplastic large cell lymphoma (BIA- Macrodissection of the FFPE section was performed for the surgical
ALCL) - case report and review of the literature specimen, but not the core biopsies.
A. Kovács1, U. Hansson1, S. Bram Ednersson1, B. Márton2, K. Helou3, T. Results: The overall percent agreement (OPA) between IHC/SISH and
Parris3, S. Janeva4 STRAT4 was 97% and 96% for ER status, 89% and 92% for PGR status,
1
Dept of Clinical Pathology, Sahlgrenska University Hospital, 76% and 77% for Ki-67 proliferation marker, and 88% and 90% for HER2
Gothenburg, Sweden, 2 NU Hospital, Dept of Pathology, Trollhättan, status in the core biopsies and matched surgical specimens, respectively. We
Sweden, 3 Dept of Oncology, Institute of Clinical Sciences, Sahlgrenska observed changes in molecular subtype for 26 patients due to discordances
Cancer Center, Sahlgrenska Academy at University of Gothenburg, in ER status (4 cases), Ki-67 status (10 cases), and HER2 status (12 cases).
Sweden, 4 Dept of Surgery, Sahlgrenska University Hospital, Institute Conclusion: Reliable ER, PGR, Ki-67 and HER2 biomarker status is
of Clinical Sciences, Sahlgrenska Academy at University of necessary when selecting optimal postoperative therapy choices for breast
Gothenburg, Sweden cancer patients. Our data suggest that not only macrodissection, but even
microdissection, can be useful to improve the OPA between IHC and
Background & Objectives: Approximately 8000 women undergo breast STRAT4. The presence of ER/PGR positive normal tissue and ER posi-
implantation in Sweden annually, with 80% as aesthetic surgery and 20% as tive and/or HER2 positive DCIS component may skew the biomarker
reconstruction after breast carcinoma treatment. Around 650 BIA-ALCL outcome.
cases have been reported in the literature to date with nine patient deaths.
BIA-ALCL incidence rates are on the rise as elective breast implantation
increases. This condition is multifactorial, primarily due to genetic factors PS-01-038
(JAK/STAT3 activation and MYC/TP53 dysregulation), Gram-negative bio- PD-L1 status in triple negative and luminal B HER2-negative breast
film around the implant, time and geographic differences. carcinomas after neoadjuvant therapy
Methods: Two patients aged 38 and 61 were diagnosed with ALK-negative G. Frank 1 , O. Kuznetsova 1 , L. Zavalishina 1 , Y. Andreeva 1 , M.
BIA-ALCL, which developed after reconstructive breast implantation. Both Shomova2, M. Vinogradov2
1
patients had delayed, non-infective fluid collection around the breast implant. FSBEI FPE RMACPE MOH Russian Federation, Russia, 2 State
BIA-ALCL was diagnosed cytologically with late chronic seroma fluid and Budgetary Institution of Ryazan Region Regional Clinical Oncological
histopathologically in the fibrous scar tissue adjacent to the implant. Dispensary, Russia
Results: The immunocyto-/immunohistochemical analysis showed posi-
tivity for CD45, CD30, CD8, CD15, granzyme, TIA-1 and perforin and Background & Objectives: To study the expression of PD-L1 in primary
negativity for ALK-1, CD3 and CD20 in the large anaplastic cells obtained tumours (PT) and metastases (MTS) of triple negative (TNBC) and lu-
from seroma fluid and identified in the fibrous capsule. Both implants had minal B HER2-negative breast carcinomas (BC).
been removed and the patients had 1- and 2-year disease-free survival. Methods: Tumour tissue samples from 42 patients with BC were used. 18
Conclusion: BIA-ALCL is a rare, but highly treatable type of T-cell patients received neoadjuvant therapy. PD-L1 expression was detected
lymphoma that can develop around breast implants, mainly with textured with Ventana PD-L1 (SP142) (Roche) antibodies on the Ventana
surfaces. Pain, swelling and induration around an implant of more than 12 BenchMark Ultra (Roche) device. 3 independent experts evaluated re-
months of age may warrant the diagnosis of BIA-ALCL. If the disease is sults. The criterion for the positive status of the tumour was full or partial
limited to the fibrous scar tissue, removal of the implant and complete membrane staining of ≥ 1% of tumour (TC) or immune intratumourall
capsulectomy is curative. Clinicians should inform patients about the cells (IC) located ≤1 mm from the tumour. PT and MTS were studied,
risks of the breast implant before surgery. statistics with X2 criterion was used.
Results: Positive expression of PD-L1 in TC was detected in 12/42 cases
(28.6%): 2/16 luminal B HER2 negative tumours (12,5%), 10/26 TNBC
PS-01-036 (38,5%). The positive IC was observed in 6/16 (37.5%) and 17/26
Comparison of immunohistochemically assessed ER, PGR, HER2, (65.5%) of cases, respectively.
and Ki-67 breast cancer biomarker status with the automated PD-L1 expression in TC was in 3/8 tumours (37,5%) with RCB III
STRAT4 RT-qPCR-based diagnostic platform - a retrospective study (p<0,05). Positive staining of IC was in 4/10 (40.0%) RCB-II and 6/8
on 100 breast carcinomas (core biopsies & matching surgical (75.0%) of RCB-III cases. PT and MTS showed differences in protein
specimens) expression, but the status matched in 100% cases
A. Kovács1, T. Parris2, S. De Lara1, S. Nasic3, S. Janeva4 Conclusion: Positive PD-L1 status was detected in 28.6% cases of triple
1
Dept of Clinical Pathology, Sahlgrenska University Hospital, negative and luminal B HER2 negative BC, with higher number of PD-
Gothenburg, Sweden, 2 Dept of Oncology, Institute of Clinical L1-positive tumours (38.5%) in triple negative subtype.
Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at Tumours with worse response to neoadjuvant therapy (according to RCB
University of Gothenburg, Sweden, 3 Research and Development score) show higher PD-L1 expression in tumour cells (p<0,05)
Virchows Arch

PS-01-039 showed a slightly higher incidence of APLs (n=18/475, 3.8%) compared

Association between clinicopathological markers and survival in hor- to the BENIGN cohort (n=13/475, 2.7%).
mone receptor-positive breast carcinoma treated with neoadjuvant Conclusion: There has been a steep improvement of suture orientation
chemotherapy signifying an increased surgical recognition of the possibility of margin
H. Lee1, W. Han2, S. Im3, T. Kim4, K. Lee4, I.A. Park5 re-excision in incidental APLs. Clinical stratification based on a number
1
Chungbuk National University College of Medicine Department of of factors such as age, family history, pre-operative imaging and known
Pathology, Republic of Korea, 2 Department of Surgery, Seoul National genetic risk may guide appropriate management of such specimens whilst
University College of Medicine, Republic of Korea, 3 Department of adopting a pragmatic approach to block-taking.
Internal Medicine, Seoul National University College of Medicine,
Republic of Korea, 4 Seoul National University College of Medicine
Department of Internal Medicine, Republic of Korea, 5 Department of PS-01-041
Pathology, Seoul National University College of Medicine, Republic of Prognostic value of CEACAM1 in breast cancer in situ
Korea M. Lyndin1, R. Moskalenko2, A. Romaniuk2, B.B. Singer3
1
Sumy State University, Medical Institute, Department of Pathology,
Background & Objectives: Residual cancer burden (RCB) is an impor- Ukraine, 2 Sumy State University, Ukraine, 3 University of Duisburg-
tant marker for patients with breast carcinoma treated with neoadjuvant Essen, Institute of Anatomy, Germany
chemotherapy (NACT). However, the association is not absolute for re-
sidual disease of hormone receptor-positive luminal type breast carcino- Background & Objectives: Ductal breast cancer can be divided into in-
ma. We analysed which clinicopathological variables including RCB vasive and non-invasive types (cancer in situ – DCIS). Although there is
grade and immunohistochemical (IHC) markers were associated with information about molecular features of these tumours, DCIS remains none
survival. fully described pathology. Thus we need to find novel reliable diagnostic
Methods: Expression of annexin-8, galectin-3, bcl-2, calreticulin, clusterin, markers. One could be the сarcinoembryonic antigen related cell adhesion
ki-67, mucin-1, and p27 were assessed in tissue microarray slides of 55 post- molecules 1 (CEACAM1). This molecule was described in diverse invasive
NACT resection specimens from luminal type breast carcinoma patients types of cancers. The aim our study presented here was to characterise the
treated by docetaxel and doxorubicin. Patients’ age (≥45 vs. <45), RCB exact expression pattern of CEACAM1 in various types of DCIS.
grade (RCB-II vs. RCB-III), lymphovascular invasion, and IHC markers Methods: The investigation was conducted on 20 samples with different
were analysed according to disease-free survival (DFS) using Kaplan- types (papillary, cribriform, solid and comedocarcinoma) and grades (low
Meier method and multivariate Cox proportional hazard model. and high) of DCIS. The presence of CEACAM1 was detected by the
Results: Ten-year DFS of all patients was 65.7%. Only ki-67 index of immunohistochemistry utilizing the mAb С5-1Х/8 (0.1μg/ml).
≥5% was associated with shorter DFS by Kaplan-Meier method Results: Low grade DCIS (papillary and cribriform) was characterised by
(p=0.021). High expression of galectin-3 showed a tendency for shorter apical expression of CEACAM1 on tumour cells which limited the lu-
DFS (p=0.1). Patients’ age, (p=0.29), RCB grade (p=0.52), mens in tumour structures. The disappearance of spaces between cells
lymphovascular invasion (p=0.44) and the other IHC markers were not (solid DCIS) was accompanied by a vanishing of CEACAM1.
associated with DFS. Multivariate Cox proportional hazard model Comedocarcinoma (high-grade DCIS) were characterised by cytoplasmic
showed that high ki-67 index was the only independent marker for shorter and uniform membranous distribution of CEACAM1 with areas of its
DFS (hazard ratio, 3.34; 95% confidence interval, 1.26-8.9; p=0.0151). absence. Some DCIS cases (cribriform, solid and comedocarcinoma)
Conclusion: Ki-67 index in post-NACT resection specimen can be a were heterogeneous: I. with and without CEACAM1; II. with different
surrogate marker for recurrence of luminal type breast carcinoma. patterns of CEACAM1 expression.
Conclusion: Ductal cancers in situ have different variants of CEACAM1
expression: papillary and cribriform – apical, solid – without CEACAM1,
PS-01-040 comedocarcinoma – cytoplasmic and uniform membranous. The growth
Prevalence of incidental atypical proliferation lesions in reduction of tumour malignancy leads to CEACAM1 distribution translocation and
mammoplasty specimens: a 6-year retrospective analysis at a tertiary their disappearance. The presence or lack of CEACAM1 cannot be indi-
breast unit cator of malignant intraductal tumours.
J. Lee1, F. Rashid1, R. Ramakrishnan1, K. Lessey1, S. Shousha1
1
North West London Pathology, United Kingdom
PS-01-042
Background & Objectives: The reported incidence of unsuspected atyp- HER2 status in breast cancer: immunohistochemistry and gene am-
ical proliferative lesions (APLs) ranges from 0.06 to 4.6% in reduction plification in the Republic of Kazakhstan
mammoplasty specimens. We aimed to calculate the prevalence of these S. Lyubko1, E. Satbaeva1
1
lesions at our tertiary breast unit. KazIOR, Kazakhstan
Methods: Data pertaining to age, gender, weight, suture orientation, laterality,
clinical indication, number of blocks and outcomes was collected by retriev- Background & Objectives: Human epidermal growth factor receptor 2
ing and analysing archived histopathology reports from 2013 to 2018. (HER2) overexpression is present in 15-20% of invasive breast cancers,
Results: 490 cases belonging to 488 patients were identified in the 6-year and is an important predictive and prognostic marker.
period (483 females, 5 males). The ages ranged from 16 to 80 years Purpose. Determination of HER2 status in patients with invasive breast
(median 48 years). A lack of 100% suture coverage was attributed to cancer (IBC).
the piecemeal nature of some surgical specimens. Of interest, the suture Methods: Immunohistochemistry (IHC) was used to study material of 745
orientation showed a steep improvement between 2016 and 2017. patients using Pathway anti-HER2/neu antibody (4B5). Equivocal HER2
There were two main cohorts: BENIGN comprising macromastia, (2+) status was specified by SISH hybridization and was performed by the
gynaecomastia and miscellaneous; and POTENTIAL MALIGNANT in- INFORM HER2 DUAL ISH DNA Probe Cocktail (USA) implementing a
cluding symmetrisation for contralateral cancer and risk-reducing mas- silver tag (HER2 gene, SISH) and a red chromogen (Chr17, Red ISH).
tectomy. 15 cases (3.1%) were eventually removed from the final analysis HER2 status by SISH was determined according with ASCO CAP
due to insufficient clinical information. Guideline 2018 as positive, if HER2/CEP17 ratio ≥2 with HER2≥6,
The most common APL was ALH/ISLN followed by FEA, DCIS, ADH HER2/CEP17 ratio<2 with HER2≥6. As a positive control for counting
and invasive carcinoma. The POTENTIAL MALIGNANT cohort signals were lymphocytes, fibroblasts, endothelial cells.
 Virchows Arch

Results: The negative HER2 (0; 1+) was determined by IHC in 566 patients. RNAs (ncRNAs). Global DNA hypomethylation results in chromosomal
Positive HER2 status (3+) was defined in 101cases. Equivocal HER2 (2+) instability, overexpression of oncogenes and reactivation of transposable
was determined in 78 patients and refined using the SISH study. In 27 (33%) elements (TE). Recently discovered Piwi-interacting RNAs (piRNAs) rep-
cases, amplification of the HER2 gene by SISH was detected. In 45 (58%) resent small noncoding regulatory RNAs that interact with the human four
cases, there was a negative result (HER2/CEN17<2, HER2<4). In 6 (7%) PIWIL1-4 RNA-binding proteins belonging to the Argonaute (AGO) fam-
cases it was not possible to assess. ily. PIWIL1-3 are germinal genes while PIWIL2-4 are both germinal and
Conclusion: The positive HER2 status of breast cancer was detected by somatic genes. PIWIL proteins are pivotal in piRNAs biogenesis and PIWI-
IHC and SISH in 128 (17%) of cases, which correlates with data from piRNA complexes constitute genetic, epigenetic and post-transcriptional
different authors. In 6 cases evaluation of HER2 status was not possible regulators implicated in genomic integrity through suppression of transpos-
due to errors in the pre-analytical stage. able elements, maintenance of germinal and somatic differentiated and stem
cells, and homeostasis via piRNA-mRNA induced activation or inhibition of
genes expression. In a small number of recent studies, deregulated expres-
PS-01-043 sion of PIWIL proteins and piRNAs was observed in various types of
Metaplastic carcinoma of the breast, about a series of 15 cases tumours. Due to contradictory results in the literature concerning expression
Z. Merad1 levels of PIWIL proteins in IBCs, we investigated PIWIL1-4 expression at
1
CHU Sidi Bel Abbes, Algeria RNA and protein levels.
Methods: We analysed PIWIL1-4 expression at RNA level by quantitative
Background & Objectives: They are tumours defined by the association RT-PCR in a large series of 526 patients who had undergone partial or
with the adenocarcinomatous component, of a squamous, sarcomatoid, complete mastectomy for unilateral invasive primary breast cancer. At protein
chondroid or osteoid contingent Described by Huvos et al. in 1973 [2]. level, study of PIWIL1-4 expression was performed by immunohistochem-
Report the rarity of this type of cancer and study its histopathological istry (IHC) in a series of 200 patients belonging to the large series.
characteristics. Results: PIWIL1-4 proteins were deregulated in IBCs with PIWIL2 and
Methods: We report a retrospective study of 15 cases of metaplasic PIWIL4 downregulation (PIWIL2: Total 48,3%, NNN 52,5%, HER2+
carcinoma of the breast collected at the Department of Anatomy and 52,1%, RH+HER2- 50,3%, RH+HER2+ 25,9%; PIWIL4: Total 43,3%,
Pathology Cytology of the CHU of Sidi Bel Abbes-ALGERIA between NNN 28,7%, HER2+ 39,7%, RH+HER2- 47,3%, RH+HER2+ 53,4%)
2008 and 2014. and PIWIL1 and PIWIL3 abnormal emergent expression (PIWIL1: Total
The average age of our series is 50 years with extremes ranging from 30 30%, NNN 25%, HER2+ 30%, RH+HER2- 31%, RH+HER2+ 21%;
years to 75 years PIWIL3: Total 6%, NNN 4,2%, HER2+ 15%, RH+HER2- 4%, RH+
The histopathological diagnosis was confirmed on operative parts mas- HER2+ 25%) at RNA level. IHC analysis revealed underexpression of
tectomy in 52% of the cases and directed on 48% of the cases. PIWIL2 (45% of IBCs) and PIWIL4 (49% of IBCs) and abnormal ex-
Results: Macroscopic examination found a hard, whitish, irregular tu- pression of PIWIL1 (35% of IBCs) and PIWIL3 (8% of IBCs).
mour with an average size of 3.3 cm (2cm-7cm), located at the level of Significant correlations were observed at RNA and protein levels for
the super-external quadrant. PIWIL2 (p = 0.0007) and PIWIL4 (p <0.0001). PIWIL1-4 mRNA ex-
Microscopic examination: the most frequent histological type was pression levels were correlated with breast cancer molecular subtypes and
metaplasic carcinoma with epidermoid differentiation in 60% of cases, classical clinicopathological prognosis factors. Compared to IBCs with
chondroitin in 20% of cases, osteoid in 13% of cases and fusiform cells in PIWIL2 and PIWIL4 normal expression, IBCs with PIWIL2 and PIWIL4
07% of cases. A high histological grade was found in 80% of SBR III downregulation were characterised by DNA and histone methyltransfer-
cases and 20% of cases were SBR grade II. ases DNMT1, Suv39H1 and HP1 lower expression, decreased H3K9me3
Conclusion: Metaplasic carcinomas of the breast are rare, aggressive and H3K27me3 repressing epigenetic marks and chromatin
tumours with poor prognosis. decondensation with abnormal expression of Alu sequences. PIWIL pro-
teins were significantly correlated with molecules involved in cancer cell
proliferation and epithelio-mesenchymal transition.
PS-01-044 Conclusion: PIWIL2 and PIWIL4 proteins downregulation in IBCs
Biopathological significance of deregulated PIWIL1-4 proteins be- could contribute to breast carcinogenesis through abnormal diffuse hypo-
longing to the PIWI-piRNA pathway in invasive breast carcinomas methylation resulting in increased transcription of TEs and reactivation of
D. Meseure1, M. Lae2, K. Drak Alsibai3, A. Nicolas1, S. Vacher4, W. numerous oncogenes, including pure germinal genes such as PIWIL1 and
Chemlali4, Y. Allory5, A. Vincent-Salomon6, I. Bieche7 PIWIL3.
1
Platform of Experimental Pathology, Department of Diagnostic and
Theranostic Medicine Institute Curie, Paris, France, 2 Department of
Pathology, Centre Henri Becquerel, INSERM U1245, UniRouen PS-01-045
Normandie Université, Rouen, France, 3 Department of Pathology, Loss of GATA3 associates with aggressive breast cancer, a basal like
CHA Andrèe Rosemon, Cayenne, France, 4 Unit of phenotype, and immune cell activation
Pharmacogenomics, Department of Genetics, Institute Curie, Paris, A.K. Myrmel Sæle1,2, A.A. Svanøe1, C. Askeland1,2, G. Knutsvik1,2, B.
France, 5 Department of Pathology, Hôpital Foch, Université Versailles- Davidsen3, T. Aas3, K. Collett1,2, I.M. Stefansson1,2, L.A. Akslen1,2, E.
Saint-Quentin-en-Yvelines, Universitè Paris-Saclay, Suresnes, France; Wik1,2
Institute Curie, CNRS, UMR144, Paris, France, 6 Department of 1
Centre for Cancer Biomarkers CCBIO, Department of Clinical
Diagnostic and Theranostic Medicine Institute Curie, Paris, France, 7 Medicine, Section for Pathology, University of Bergen, Norway, 2
Unit of Pharmacogenomics, Department of Genetics, Institute Curie, Department of Pathology, Haukeland University Hospital, Bergen,
Paris, France and Faculty of Pharmaceutical and Biological Sciences, Norway, 3 Department of Surgery, Haukeland University Hospital,
Paris Descartes University, Paris, France Bergen, Norway

Background & Objectives: Invasive breast carcinomas (IBC) are highly Background & Objectives: GATA3 is linked to estrogen receptor biology,
heterogeneous malignant tumours, and triple-negative subtype (TNC) re- and low GATA3 associates with aggressive features in several tumours. Also,
mains a major cause of death in women. Epigenetic abnormalities are early GATA3 is suggested to play a role in activation of immune cells. We exam-
events in carcinogenesis that associate heterogeneity of DNA methylation, ined how GATA3 relates to breast cancer phenotypes and markers of immune
post-transcriptional modifications of histones and deregulation of noncoding cell activation.
Virchows Arch

1
Methods: Two breast cancer (BC) cohorts were analysed. Cohort-I: Jagiellonian University, Collegium Medicum, Chair of Pathomorphology,
Hordaland County; <70 years; n=565. Immunohistochemical staining of Poland, 2 Jagiellonian University, Collegium Medicum, Chair of General,
GATA3 on tissue microarrays of formalin-fixed paraffin-embedded BC tis- Oncological and Gastrointestinal Surgery, Poland
sue, scored by staining index (SI; 0-9). Cohort-II: mRNA data from
METABRIC and TCGA (n=2283), including BRCA 1/2 germline mutations. Background & Objectives: Sentinel lymph nodes (SLNs) are the first
Results: Low GATA3 protein and mRNA expression associated with lymphoid organs on the lymphatic drainage from primary breast tumours
aggressive tumour features, such as high histologic grade, larger tumour and constitute the front line of immune defense against cancer. Dendritic cells
diameter, ER and PR negativity, and HER2 positivity (all P≤0.001). (DCs) are the most potent antigen-presenting cells that in SLNs present
Further, low GATA3 associated with high proliferation (by Ki67), triple tumour-derived antigens to lymphocytes. Depending on their maturation state
negative and basal-like phenotypes, and reduced survival (P≤0.005). Low DCs may either evoke anti-cancer response or induce immune tolerance.
GATA3 also predicted BRCA1 germline mutations (OR=7.3; 95% CI2.2- Methods: In our study CD1a and DC-SIGN-positive DCs were identified
24.2). GATA3 expression correlated negatively with a luminal progenitor by immunohistochemistry and their densities were investigated in cortical
cell score, and positively with a mature luminal cell score (R2=0.66 and areas of 119 SLNs excised from invasive breast cancer patients with
0.70, P<0.001). Further, low GATA3 expression associated with activa- regard to metastatic burden in lymph nodes.
tion of immune cell scores, and higher PD-1, PD-L1, CTLA4, and Results: We observed that DC-SIGN+ DCs are more numerous in
FOXP3 expression (P≤0.006). macrometastatic than in micrometastatic SLNs (p<0.003) and their percent-
Conclusion: Low GATA3 is a marker for aggressive BC, a basal-like profile age in SLN tissue positively correlated with size of metastasis (R=0.4,
and reduced survival, and points to BRCA1 germline mutations. Loss of p=0.040). In contrast, CD1a+ DCs tended to decrease from negative SLNs,
GATA3 associated with immune cell activation, and the potential of SLNs with micrometastasis to SLNs with macrometastasis (p=0.055).
GATA3 as predictive marker for immunotherapy should be further elucidated. Conclusion: Therefore, we conclude that the densities of mature DC-
SIGN+ DCs increase with higher metastatic burden, while immature
Supported by Research Council of Norway and Helse Vest. CD1a+ DCs are associated with less advanced nodal stage.

Supported by Jagiellonian University grant K/ZDS/006392.

PS-01-046
Fascin-1 expression in breast cancer identifies patients with high risk
for disease recurrence PS-01-048
A. Nonni1, E.C. Tampaki2, A. Tampakis2, P. Efstratios1, K. Kontzoglou2, The predictive role of stromal CD10 expression in invasive breast
G. Kouraklis2 cancer treated with neoadjuvant chemotherapy
1
1st Dept of Pathology, Medical School, National and Kapodistrian O. Olah-Nemeth1, E. Majlat1, G. Kelemen2, R. Koszo2, A. Voros1
University of Athens, Greece, 2 2nd Department of Propedeutic 1
University of Szeged - Department of Pathology, Hungary, 2 University
Surgery, Medical School, National and Kapodistrian University of of Szeged - Department of Oncotherapy, Hungary
Athens, Greece
Background & Objectives: The therapeutic strategy of invasive breast
Background & Objectives: Breast cancer stem cells are considered to be cancer is based on routine histopathological tissue markers (estrogen-, pro-
a major cause of disease recurrence in breast cancer, as they appear to be gesterone receptor, HER2/Neu, Ki67) that are evaluated in tumour cells.
chemo-resistant. Fascin-1 is a stem cell marker, its excessive expression However, the assessment of cancer stroma could be indispensable in thera-
in tumours is associated with aggressive tumour phenotype. The aim of peutic strategy designation. Studies have shown that stromal expression of
the present study was to investigate the expression patterns of fascin-1 in CD10, a zinc-dependent metalloproteinase, is associated with biological ag-
breast cancer and to assess its possible clinical significance. gressiveness of the tumour. In the present retrospective study we aimed to
Methods: Expression of fascin-1 was assessed via immunohistochemis- evaluate CD10 expression and association between CD10 expression and
try in surgical specimens of a cohort comprised of 127 patients with response to neoadjuvant chemotherapy in invasive breast cancer.
resectable breast cancer. Results were correlated with clinicopathological Methods: A total of 60 invasive breast adenocarcinomas were included.
characteristics and survival data. Progression free survival was defined as CD10 immunohistochemistry was performed on core biopsies taken be-
the primary outcome of the present study. fore the neoadjuvant therapy. Stromal CD10 expression was determined
Results: Fascin-1 expression was strongly associated with the presence and compared with well-known predictive and prognostic tissue markers
of triple negative cancers (p<0.0001). Tumours displaying high expres- as well as with groups defined according to the degree of tumour regres-
sion of fascin-1 presented correlations with high tumour grade (p=0.002) sion into no regression, partial regression and complete regression group.
and high expression of Ki-67 (p=0.004). No statistically significant cor- Results: The number of CD10 positivity tumours was significantly higher in
relations were observed between fascin-1 expression and the stage of “no regression” group (p=0,019), thus stromal CD10 expression was found to
tumour (p=0.196) or the presence of lymph node metastasis (p=0.415). be significantly associated with decrease in response to neoadjuvant chemo-
Patients with a high expression of fascin-1 demonstrated significantly therapy, and increase in primary tumour size. No correlation was found be-
higher rates of disease recurrence or death. More specifically, 5-year tween CD10 expression and routine prognostic markers or tumour grade.
PFS was 51.8%, [95%CI] =33-52 for patients displaying high expression Conclusion: Based on our data, CD10 expression can serve as an indepen-
of fascin-1 in cancer cells versus 70.1%, [95%CI] =46-75 for patients dent predictive marker for the effect of neoadjuvant chemotherapy in breast
with low expression of fascin-1 (p=0.032). cancer patients. Therefore we propose to add CD10 immunohistochemistry
Conclusion: Expression of fascin-1 in breast cancer cells is associated to the routine dataset of prognostic and predictive markers for more precise
with a significantly worse 5-year progression free survival recognizing assessment of patient-based and tumour-specific therapeutic strategy.
therefore a group of patients with high risk for early disease recurrence.

PS-01-051
PS-01-047 HER2 gene amplification association with protein expression in
Differences in densities of sentinel lymph node CD1a and DC-SIGN- equivocal (HER2 IHC 2+) breast carcinomas: consequences of cell-
positive dendritic cells with respect to type of breast cancer by-cell analysis on HER2 gen protein assay (GPA) slides
metastasis G. Pekar1
J. Szpor1, A. Glajcar1, D. Hodorowicz-Zaniewska2, K. Okoń1 1
Department of Oncology and Clinical Pathology, Lund University, Sweden
 Virchows Arch

Background & Objectives: Identifying eligible cases for targeted thera- carcinomas on CNB turned into negative on OEB. The CNB negative-OEB
py in the human epidermal growth factor receptor 2 (HER2) immunohis- positive discrepancy was observed in carcinomas with large extent (> 40
tochemistry (IHC) 2+ breast carcinoma group is challenging for the pa- mm), higher histological grade (grade 2-3) and the majority with unifocal
thologists due to intratumoural heterogeneity when multiple subclones of distribution, while CNB positive-OEB negative mismatch occurred mainly in
tumour cells co-exist. In this study, our main aim was to find an eventual extensive multifocal tumours with lower histological grade (grade 2).
correlation between HER2 and CEP17 related parameters in different Interestingly, one IHC 3+ case was not amplified in CNB, and two IHC 3+
histological- and molecular phenotypic groups and revealing the associ- cases were equivocal with GPA in OEB series.
ation between the HER2 gene amplification and the translated protein Conclusion: Insufficient HER2 status agreement was detected between
expression intensity at a cellular level. preoperative biopsies and corresponding resected breast tumours with
Methods: Clinicopathological data were retrospectively identified from significant discordance for important prognostic and predictive bio-
women diagnosed with primary HER2 2+ IHC breast cancer at the markers, particularly HER2. We still recommend the postoperative
Department of Oncology and Pathology Lund, between a period 2015- HER2 status reassessment in the future, but on the other hand the histo-
2017. The cohort comprised 122 cases assessing 1000 cells in each tu- pathological parameters such as extent, distribution and grade must be
mour by recording the HER2, chromosome enumeration probe 17 taken into consideration for proper neoadjuvant treatment planning.
(CEP17) copies and the intensity of protein expression individually in
all the tumour cells on reflex HER2 GPA slides. The HER2 testing was
performed according to international guidelines. PS-01-053
Results: The average HER2 and CEP17 values showed a tendency to in- Three types of truncating CHEK2 germline mutations may differ by
crease with histological grade in breast cancer with no special type (NST) the frequency of somatic loss of the wild-type allele
histology though in NST grade 2 tumours with higher average CEP 17 value G. Raskin1, A. Iyevleva2, S. Aleksakhina2, A. Sokolenko2, A. Ivantsov2,
than in NST grade 3 carcinomas (2.23 and 2.16, respectively). Still, the E. Imyanitov2
1
tendency seems apparent there was no significant difference between histo- Academic A.M. Granov Scientific Center for Radiology and Surgical
logical tumour types and grades (p=0.146 to p=0.992). The HER2 copy Technology, Russia, 2 N.N. Petrov Institute of Oncology, Russia
numbers positively associated with protein expression intensity in the ma-
jority of tumour types and grades (pNSTgrade2= 0.040). Luminal A- and B-like Background & Objectives: Germline mutations in CHEK2 gene repre-
tumours showed the same positive correlation (pLuminalA<0.0001, sent the second most frequent cause of hereditary breast cancer (BC) after
pLuminalB=0.250), however in hormone receptor negative (HR-) carcinomas BRCA1 lesions. However, clinical and biological properties of CHEK2-
the inverse phenomenon was detected, namely the highest mean HER2 associated BC remain poorly studied.
values were observed in a non-protein expressing cells. Methods: Clinical, immunohistochemical and molecular characteristics
Conclusion: As a result of our findings we propose that: following inter- were compared in BCs obtained from carriers of distinct CHEK2 muta-
national guidelines search and count HER2 and CEP17 copies in tumour tions (1100delC: n = 29; 5395del: n = 39; IVS2+1G>A: n = 23).
cells with the most intensive protein expression, regardless of tumour Results: BC associated with three types of truncating mutations had similar
types, paying more attention to tumours with higher histological grade. clinical and immunohistochemical features. Somatic loss of the wild-type
In HR- breast carcinomas consider HER2 overexpressing and non- allele was more frequent in CHEK2 5395del-associated tumours (10/18,
expressing cells for proper evaluation. 56%) than in BC from 1100delC (2/15, 13%) or IVS2+1G>A (2/13, 15%)
mutation carriers (5395del vs. 1100delC+IVS2, p = 0.007). Mutant and
wild-type CHEK2 alleles demonstrated similar levels of mRNA expression
PS-01-052 in BC without CHEK2 loss of heterozygosity (LOH). Exome sequencing
The accuracy of HER2 status establishment between core needle and revealed that CHEK2 LOH was associated with evident genomic instability.
open excision biopsy in breast cancer: multi-Institutional study from Conclusion: Hereditary breast tumours associated with three types of
southern Sweden CHEK2 truncating mutations may develop by different molecular mech-
N. Mylona1, C. Dekany1, G. Pekar1 anisms. It is important to determine, whether the substantial frequency of
1
Department of Oncology and Clinical Pathology, Lund University, CHEK2 LOH in 5395del-driven tumours results in a specific pattern of
Sweden chemosensitivity of this category of BC.

Background & Objectives: Human epidermal growth factor receptor 2 This work has been supported by the Russian Foundation for Basic
(HER2) status testing is a crucial part of breast cancer diagnostics and treat- Research (grant number 17-29-06046).
ment. Tumour size, extent of in situ carcinoma component, histological grade,
spatial distribution, as well as hormone receptor (HR) status could affect
HER2 result in core needle biopsy (CNB) compared to open excision biopsy PS-01-054
(OEB). The aim of this study was to investigate the concordance rate between Significance of intratumoural HER-2 heterogeneity in invasive
biomarkers in pre-operative CNB and corresponding OEB with emphasis on breast carcinomas
HER2 status discrepancy in relation to histopathological parameters. P. Ravazoula1, D. Koumoundourou1, E. Nikolatou2, G. Michael3
1
Methods: Clinicopathological data were recruited from women diagnosed University Hospital of Patras, Greece, 2 Faculty of Health & Caring
with primary invasive breast cancer at the Department of Clinical Oncology Professions, Technological Educational Institute of Athens, Greece,
3
and Pathology, Lund and Malmö University, Sweden during 2014-2018. Department of Obstetrics & Gynaecology, Patras University Medical
The cohort comprised 419 cases matching histological grade, immunohisto- School, Achaia, Greece
chemistry (IHC) based biomarkers including HER2 gen protein assay (GPA)
and/or fluorescence in situ hybridization (FISH) on preoperative CNB and Background & Objectives: Breast cancer is an heterogenous disease.
postoperative OEB from the same tumour according to guidelines. Several hypotheses have been proposed to explain the origin of
Results: HER2 IHC scores with reflex GPA/FISH analysis revealed 378 intratumoural heterogeneity, but besides the differences between tumours
negative cases and 25 positive cases in both CNB and OEB equaling a cancer cells within one tumour of a patient at any given time frequently
concordance rate of 96.2% with a substantial agreement (Cohen`s κ= display intratumoural heterogeneity. The heterogeneity in biomarker ex-
0.738). Notably, 16 tumours (3.8%) showed discordant HER2 status with pression among neoplastic cells might be attributed to several plausible
CNB negative-OEB positive mismatch in 11 cases (2.6%) and CNB events and procedures during tumour progress (angiogenesis, tissue infil-
positive-OEB negative mismatch in 3 cases (0.7%). Additionally, 2 equivocal tration, metastasis). Several studies focusing on the differential
Virchows Arch

parenchymal expression of cellular biomarkers with prognostic or predic- process primarily were represented in the group with complete remission. On
tive value have been recently published; efforts addressing HER-2 protein the other hand, cell adhesion process, cytoskeleton organization process, ves-
immunoexpression aim in targeted therapeutic interventions. icle organization process and Golgi organization process overrepresented in
Methods: The expression of the HER-2 molecule has been studied in tissue breast cancer which showed poor responses to the therapy. The machine
specimens originating from eighty breast cancer patients. learning approaches using Random Forest algorithm demonstrated the
Immunohistochemical detection of HER-2 protein has been carried out in highest AUC value, 0.978 (sensitivity 1.0 and specificity 0.714) with a com-
pairs of two separate blocks material originating from the same core biopsy. bination of 11 proteins including STUB1, PDCD6, YARS, MAOB, PDCD4,
The intensity of immunoexpression has been graded with a practical scoring NA, FLYWCH2, ABAT, FAM162A and WARS (Figure00, Table 00). For
system (0-1+: negative staining, 2+: equivoval and 3+:positive staining). the accuracy prediction, four different algorithms demonstrated evenly high
Results: In 47 out of eighty studied paired samples, matching results have accuracy rates from 0.85 to 0.95 with a combination of STUB1, PDCD6,
been obtained. In the remainder 21 (26.2%) a slight difference in YARS, MAOB, WARS, RHBDF1 or KIAA1522. the selected seven candi-
immunoexpression has been documented (score 0/1+ and 2+, respective- dates (KIAA1522, RHBDF1, WARS, YARS, MAOB, STUB1 and PDCD6)
ly) among the paired samples, while in 12/80 (15%) a significant differ- evaluated in the subsequent steps of verification using immunohistochemistry
ence has been observed (score 1+/2+ and 3+, respectively). In most cases (IHC) in 123 patient cohorts. The predictive relevance of individual proteins,
the findings have been confirmed with in situ hybridization. YARS and RHBDF1 to distinguish CR from nCR was AUC of 0.605 and
Conclusion: Our results corroborate the presence of heterogenous 0.630 for all cases and approximately 10.2% higher AUC in luminal breast
intratumoural expression of HER-2 protein, as suggested by previous studies. cancer (AUC=0.749 and 0.717). The overexpression of YARS induced che-
These findings underscore the necessity of assessing HER-2 motherapeutic sensitivity in hormone receptor-positive breast cancer cell lines
immunoexpression in several tissue blocks due to the challenge for treatment such as T47D, which was confirmed with multiple molecular biology-driven
selection when aiming to individualize patient’s optimal therapeutic approach. assays. The further experimental model of breast cancer demonstrated that
YARS induced tumour necroptosis which enhanced chemotherapy response
and was synergized with a combination of SMAC mimetics that is a potent
PS-01-055 necroptosis inducer.
Tyrosine aminoacyl-tRNA synthetase sensitises breast cancer to che- Conclusion: Our current study is the first report that confirmed the presence
motherapy through Smac mimetics derived necroptosis mechanism: of YARS enhances a profound chemotherapeutic effect which is mediated by
high-throughput proteomics and machine learning algorithm based necroptosis in breast cancer in addition to the reliable predictive biomarker for
feature selection analyses chemotherapy response. In addition, a combination of YARS plus a Smac
H.S. Ryu1, D. Han2, K. Lee3, K. Kim4 mimetic LCL161 led to a significant improvement in breast cancer response
1
Department of Pathology, Seoul National University Hospital, Republic to chemotherapy. Smac mimetics are recently developed necroptosis inducer
of Korea, 2 Proteomics Core Facility, Seoul National University Hospital, and considered as promising therapeutic targets that antagonize IAP proteins
Republic of Korea, 3 Biomedical Research Institute, Seoul National which have been known to be linked to treatment failure and unfavourable
University Hospital, Republic of Korea, 4 Division of Clinical prognosis in various malignant tumours. Currently, Smac mimetics are un-
Bioinformatics, Biomedical Research Institute, Seoul National dergoing in multiple clinical trials to overcome treatment resistance or as
University Hospital, Republic of Korea cancer therapeutics In the previous study, Smac mimetics triggers necroptosis
when caspase 8 is inactivated in acute myeloid leukemia cell line, which is
Background & Objectives: Although more than 70% of entire patients consistent with our data where caspase 8 was inactivated by YARS overex-
are currently receiving the chemotherapy regimen, pathologic complete pression. Our present study also confirmed that YARS combined with Smac
response (CR) rate is still low, ranging from 23% to 32.7%. Therefore, the mimetics triggered MLKL and RIP phosphorylation which are downstream
need for a marker predictive of response to a particular cytotoxic regimen, effectors of necroptosis and induces plasma membrane permeability and cell
especially before neoadjuvant chemotherapy, is becoming all the more death. In summary, our discovery data provide a global molecular landscape
necessary to optimise therapeutic efficacy and to avoid unnecessary com- for determining chemotherapy response in breast cancer at the proteome level.
plications caused by systemic therapy. Furthermore, we provided a novel protein candidate to predict chemotherapy
Methods: We performed quantitative proteomics mass spectrometry in response and identify a novel protein YARS in combination with Smac
twenty paired FFPE biopsy breast cancer samples consist of non- mimetics synergistically induced necroptosis which produces more cell death
responsive and responsive groups to chemotherapy. To define the best clas- in response to combined chemotherapy in breast cancer.
sifier to evaluate the predictive power of signatures, we employed four
different machine learning algorithms and performed repeated cross- NRF funded by the Ministry of Science, ICT & Future Planning
validation on the training set to classify samples between pathologic com- (2018R1A1A1A05077484) KHIDI funded by the Ministry of Health &
plete response (CR) and non-complete response (nCR) groups. The candi- Welfare, Republic of Korea (HI17C0048).
date proteins selected from the machine-learning algorithms were subse-
quently validated by immunohistochemistry of 123 cases of independent
needle biopsy FFPE samples which obtained before chemotherapy. The PS-01-056
further experimental model of breast cancer was performed to identify the Prognostic role of immunological markers in triple negative breast
molecular mechanism of how the biomarker potentiates sensitivity of multi- carcinoma
ple breast cancer cells to chemotherapy response and synergistic effect with a H. Sahin Ozkan1, M.U. Ugurlu2, H. Kaya1
1
combination of necroptotic mimetics. Marmara University Faculty of Medicine, Department of Pathology,
Results: The mass spectrometry-based proteomic analysis of FFPE set Turkey, 2 Marmara University Faculty of Medicine, Department of
yielded 6,069 protein groups. The filtered dataset was subjected to statistical General Surgery, Turkey
analysis using Student’s t-test (p-value < 0.05), which resulted in 539 proteins
with differential abundances. To identify the most meaningful changes in two Background & Objectives: Composition and interactions of tumour-
conditions, the volcano plot was used. 13 proteins including YARS, immune-microenviroment (TIME) has become ever more important for
TBC1D10C, SMCHD1, WARS, IGKV3-15, HTATIP2, KIAA1522, the management of triple negative breast carcinoma (TNBC). Our aim is
MAOB, MAPT, BSPRY, CAP2, ABAT, and NAT1 were prioritized. We to evaluate the relationship between CD8, FOXP3, PD-L1, CD163 and
searched for biological process in the Gene Ontology (GO) enrichment anal- histopathological parameters to understand their prognostic role.
ysis in each proteomic cluster. Several immune responses process, apoptotic Methods: 51 lumpectomy/mastectomy specimens, which had been
process, DNA replication process, and aminoacylation for protein translation diagosed as TNBC and not received neo-adjuvant therapy, were
 Virchows Arch

immunostained with CD8 (C8/144B-Dako), FOXP3 (EP340-Epitomics), Background & Objectives: Male breast cancer (MBC) is a rare con-
PD-L1 (SP263-Ventana), and CD163 (EP324-Epitomics). CD8, FOXP3, dition representing the 0.5-1% of all breast cancer cases. In contrast
and CD163 expressions were separately evaluated in intratumoural(IT) to female breast cancer (FBC), relatively little is known about MBC.
and stromal(S) areas. PD-L1 expression was also individually considered Most MBCs are luminal A or B types, whereas basal-like and HER2
in neoplastic cells (NC) and tumour-infiltrating-lymphocytes (TIL). enriched types are rare. This distribution is clearly different com-
Results: All patients were female. Mean age was 52.7 (32-84) and mean pared to FBC, pointing to possible important differences in carcino-
survival was 48.3 months (3.4-83.7). There was a significant positive corre- genesis. Increasing data deal with the role of the androgen receptor
lation between the expressions of each of the four antibodies (p<0.01). (AR) as a marker of prognosis in FBC, with contrasting results. Since
Among the histological subtypes, higher expressions of CD8 (IT), FOXP3 the androgen – AR signalling exerts actions on key events during
(IT&S), PD-L1 (NC), and CD163 (IT&S) were found in lymphocyte- prostate carcinogenesis, the aim of the present study was to evaluate
predominant breast carcinomas (p<0.05). Expressions of CD8, FOXP3, and the role of AR in MBC.
CD163 (IT&S), and PD-L1 (TIL) were negatively related to angio and lym- Methods: 23 males with a diagnosis of invasive breast cancer were
phatic invasion (p<0.01). Perineural invasion was more frequent in the cases selected. Clinico-pathological data were collected. AR expression
with lower CD8 (S) and FOXP3 (IT&S) and higher PD-L1 (TIL) expressions was measured by immunohistochemistry (SP107, Ventana Medical
(p<0.01). pT stage was reversely related to CD8 (S) and PD-L1 (TIL), how- Systems; Ventana BenchMark AutoStainer). Pathological variables
ever, it had a positive association with PD-L1 (NC) and CD163 (IT) (p<0.01). were compared by Spearman’s rank correlation coefficient.
Lower expressions of FOXP3 (IT&S), PD-L1 (TIL), and CD163 (IT) were Moreover, the Kaplan–Meier method and log-rank test were used
observed to be related with exitus (p<0.01). Local recurrence was negatively to explore the impact of AR expression on disease free survival
associated with CD8 (S), FOXP3 (IT), PD-L1 (TIL), CD163 (S) (p<0.01). (DFS).
Expressions of CD8 (S), FOXP3 (IT&S), PD-L1 (NC&TIL), and CD163 Results: 16 out of 23 patients (70%) displayed and increase of AR ex-
(IT&S) were lower in the cases with distant metastasis (p<0.01). pression with the increase of Progesterone Receptor (PgR) expression
Conclusion: TIME is an important prognostic parameter and a potential (rho = 0,484; p = 0,019). Instead, 7 out of 23 patients (30%) with low
therapeutic marker. CD8, FOXP3, PD-L1, and CD163 antibodies are levels of PgR displayed high levels of AR with a potential advantage in
useful to consider TIME and to predict prognosis in TNBC. terms of DFS (p=0,081).
Conclusion: These preliminary data suggest a possible prognostic role of
AR in MBC. Forthcoming molecular analysis will shed light to unknown
PS-01-057 underlying mechanisms.
Relationship of Her2/neu and oestrogen receptor changes in local
metastases compared with primary tumour in breast cancer patients
with equivocal (2+) Her2/neu expression level in primary tumour PS-01-059
S. Sazonov1, K. Konyshev2 Expressed cartilaginous and osseous metaplasia in breast cancer:
1
Institute of Medical Cell Technologies, Russia, 2 Institute of Medical histological and immunohistochemical aspects
Cell Technologies, Ural State Medical University, Russia V. Sikora1, M. Lyndin2, N. Hyriavenko1, R. Moskalenko3, A. Piddubnyi3,
L. Karpenko1, A. Romaniuk3
1
Background & Objectives: Differences in the expression of biomarkers Sumy State University, Medical Institute, Pathology Department,
in primary tumour tissue and metastases and the relationships of such Ukraine, 2 Sumy State University, Medical Institute, Department of
differences in breast cancer patients are not clear until now. Objective: Pathology, Ukraine, 3 Sumy State University, Ukraine
to reveal the relationship of estrogen receptor (ER) and Her2/neu changes
in locoregional metastases compared with primary tumour in the group of Background & Objectives: The course of the breast cancer (BC)
breast cancer patients with equivocal Her2/neu expression level (2+). depends on the differentiation of the tumour, immunophenotype of
Methods: 19 samples of primary tumour (Her2/neu expression 2+) and the neoplastic cells and the qualitative and quantitative characteris-
corresponding metastases were stained immunohistochemically with tics of the tumour microenvironment. Moreover, the expressed sec-
anti-ER (1D5, Dako) and anti-Her2/neu (4B5, Ventana) antibodies. ondary changes significantly influence on the progression of the
Primary tumour samples were additionally analysed using SISH technol- malignant process in the mammory gland. We present the case of
ogy (Ventana). Staining results were evaluated using Allred score and the invasive breast cancer (non-specific type) of the right breast in a
ASCO/CAP 2013 guideline. Frequencies of Her2/neu and ER expression 64-year-old woman with the features of the expressed rare type of
changes were compared using Fisher’s exact probability test. metaplasia.
Results: Her2/neu expression level was lower in metastases then in the Methods: Morphogenesis and immunophenotype of the tumour were
primary tumour in 16 cases (84,2%, 95% CI 59,5-95,8%) and higher – in studied by using the histological (H&E) and immunohistochemical
1 case out of 19 (5,3%, 95% CI 0,3-28,1%) (p<0,001). Her2/neu-statuses (CKpan, Er, Pr, PRL, Her2neu, Ki-67, EGFR, MPO, GPA, CD3,
of primary tumour and metastases were the same in 84,2% (95% CI 59,5- CD79, CD68, OPN and OSN) methods.
95,8%) of cases. Among 16 cases with decreased Her2/neu expression Results: The high-grade invasive cancer of non-specific type with
level in metastases we registered 9 cases with increase and 2 cases with the expressed cartilaginous and osseous metaplasia was diagnosed.
decrease of ER expression level (p=0,023). Immunohistochemical study revealed the strong expression for
Conclusion: We found simultaneous decrease of Her2/neu expression lev- CKpan, OPN, OSN, PRL, moderate-EGFR, weak-Er, negative-Pr
el, maintenance of Her2/neu-status and increase of ER expression level in and Her2neu in the cancer tissue; Ki-67 expression was found in
local metastases compared with primary tumour of breast cancer in the 7% of tumour cells. In the areas of osseous and cartilaginous tis-
cases with equivocal (2+) Her2/neu expression level in the primary tumour. sue, the accumulation of single CD3, CD79α vs CD68 positive
cells with MPO and GPA positive cells was revealed which con-
firms the formation of red bone marrow in the centre of
PS-01-058 metaplasia.
Androgen receptor expression as a possible prognostic marker in Conclusion: This clinical observation presents the case of the
male breast cancer breast cancer, where the immunophenotype of cancer cells is the
C. Scatena1, R. Scarpitta1, R. Biancotti1, L. Diodati2, M. Ghilli2, A.G. indicator of the possible osteo/chondrogenesis with the formation
Naccarato1 of bone marrow. Timely determination of the expression peculiar-
1
University of Pisa, Italy, 2 University Hospital of Pisa, Italy ities of immunohistochemical markers in cartilaginous and osseous
Virchows Arch

metaplasia makes it possible to predict the course of the oncolog- Methods: All men diagnosed with invasive breast carcinoma in 6 inter-
ical disease and its metastasis. national Institutions (1999- 2015) were identified by searching laboratory
databases. Parameters analysed were the followings: age, tumour size,
histological tumour type and grade, molecular biomarkers (ER, PR, ki-
PS-01-060 67, HER2), AR status, treatment and length of OS (months).
Clinicopathological and immunohistochemical characterisation of Results: 217 cases, with a mean age of 62y (range: 18- 85), right breast
adenoid cystic carcinoma of the breast diagnosed in a single localization (52.53%), NST histological type (86.18%), G2 histological
Institution grade (55.4%), T2 (54.41%), N+ (65.89%) and Luminal A molecular
M. Souto Moura1, G. Satta2, M. Jácome1, P. Lopes1, F. Silva1, M.J. subtype (85.29%) were identified. 5-year OS was 67.2% and 10-year
Bento1, C. Leal1 OS was 48.5%. OS was 92.7% at 5 years and 73.8% at 10 years (in
1
Department of Pathology, IPO-Porto, Portugal, 2 Department of axillary lymph node negative cases) while OS was 59.7% at 5 year and
Medical, Surgical and Experimental Sciences, Unit of Pathology, 41.3% at 10 years in axillary positive male cancers (p=0.003).
University of Sassari, Italy

Background & Objectives: Adenoid cystic carcinoma (ACC) is a rare PS-01-062

but distinct breast neoplasm resembling its counterpart in other organs. It is Higher tumour cell proliferation in breast cancer of the young
architecturally heterogeneous and composed of a dual cell population, A. Svanoe1, G. Knutsvik1,2, B. Davidsen3, C. Askeland4,2, K. Krüger1, T.
expressing epithelial and myoepithelial markers. Nevertheless, there is Aas3, I.M. Stefansson4,2, L.A. Akslen4,2, E. Wik4,2
1
some controversy in the literature regarding its immunohistochemical pro- Centre for Cancer Biomarkers CCBIO, Department of Clinical
file. The aim of this study was to characterise the clinical, histological and Medicine, University of Bergen, Norway, Norway, 2 Department of
immunohistochemical features of ACC cases diagnosed in our Institution. Pathology, Haukeland University Hospital, Bergen, Norway,
3
Methods: A retrospective analysis of patients with ACC of the breast in Department of Surgery, Haukeland University Hospital, Bergen,
our Institution was carried out. Twelve cases were included (1987-2018). Norway, 4 Centre for Cancer Biomarkers CCBIO, Department of
Histological pattern and Nottingham Histological Grade (NG) were eval- Clinical Medicine, Section for Pathology, University of Bergen, Norway
uated. Immunohistochemistry with hormonal receptors (estrogen-ER and
progesterone-PR), human epidermal growth factor receptor type 2 Background & Objectives: Breast cancer (BC) in adolescents and
(HER2), p63, calponin, vimentin, S100, smooth muscle actin (SMA), young adults (AYAs; 15-49 years) is associated with aggressive tumour
CK7, CAM5.2, CK5/6, CD117 and CK14 was performed for each case. features. We aimed to investigate tumour cell proliferation in AYAs.
Results: Mean tumour size was 2,2cm. NG was 1(n=7), 2(n=3) and Methods: The proliferation marker Ki67 was analysed by immuno-
3(n=1). Six cases were predominantly tubular/cribriform and six had histochemistry on FFPE TMA-slides from two population based co-
solid/basaloid areas. 75% were triple-negative. All cases stained for horts: One AYA series (n=355) and one series of patients aged 50-69
CK7 and vimentin and eleven for CD117 and p63, each. Remaining (n=546). mRNA data from METABRIC and TCGA (n=2283) was
markers stained variably. In predominantly tubular/cribriform tumours used to investigate gene expression signatures reflecting tumour
CK7, CD117, p63 and vimentin clearly identified two different cell pop- proliferation.
ulations. In solid tumours there was more epithelial-myoepithelial stain- Results: The AYAs demonstrated higher Ki67 levels compared to BC
ing overlap with these markers. NG3 case was the only with nodal and patients ≥ 50 years (median Ki67 10.4% and 7.0%, respectively;
distant metastasis. P<0.0005). Higher Ki67 levels were found among AYAs <40 years com-
Conclusion: ACC has good prognosis and characteristic histological and pared to those 40-49 years (median Ki67: 16.0% and 9.0%, respectively;
immunohistochemical features. Nevertheless, in tumours with predomi- P=0.009). High levels of Ki67 among AYAs were associated with high
nantly solid/less differentiated areas there is more histological and immu- histologic grade, ER and PR negativity, larger tumour diameter, and
nohistochemical heterogeneity, which makes the differential diagnosis shorter survival (all P<0.0005). When adjusting for tumour size, histo-
with other basaloid salivary gland-like carcinomas of the breast more logic grade and lymph node status, Ki67 maintained independent prog-
challenging. nostic impact, also among ER positive AYA tumours. Higher mRNA
proliferation scores in the young, and associations between high scores
and shorter survival, validated our results (all P<0.0005).
PS-01-061 Conclusion: BC of the young demonstrate higher tumour cell prolifera-
Analysis of clinical-pathological data with impact on overall survival tion compared to older patients, and higher proliferation associate with
(OS) in male breast carcinoma (MBC): an international multi- aggressive tumour features and reduced survival among AYA patients.
Institutional study of 217 cases This might contribute to the more aggressive breast cancers observed in
S. Stolnicu1, E. Restekova2, A. Dema3, M. Comanescu4, I. Alvarado- the young.
Cabrero5, R. Buiga6, M. Boros7
1
Department of Pathology, UMFST, Targu Mures, Romania,
2
Department of Pathology, MD Anderson Cancer Center, Houston, PS-01-063
USA, 3 Department of Pathology, Emergency Clinical County Hospital Is breast cancer different in women younger than 40 years old?
"Pius Brinzeu", Timisoara, Romania, 4 Department of Pathology, "Victor I. Uglai1, F. Voaides-Cojan2, A. Budica2, B.R. Nataras1, C. Ciora3, G.E.
Babes" Institute, Bucharest, Romania, 5 Department of Pathology, Olteanu4,5, C. Suciu2,6, D. Anderco1, D. Grujic2,6, C. Lazureanu7,8, A.
Hospital de Oncología Mexico City, Mexico, 6 Department of Dema9
1
Pathology, Oncologic Institute "I. Chiricuta" Cluj, Romania, Emergency Clinical County Hospital ''Pius Brinzeu'' Timisoara,
7
Department of Pathology, University of Medicine and Pharmacy, Romania, 2 "Pius Brânzeu" Emergency County Hospital, Timisoara,
Oradea, Romania Romania, 3 Department of Pathology, University of Medicine and
Pharmacy "Victor Babes", Timisoara, Romania, 4 Department of
Background & Objectives: Male breast carcinoma is still inadequately Pathology, University of Medicine and Pharmacy "Victor Babes",
characterised and data regarding the impact of different prognostic pa- Timisoara, Romania, 5 Centre for Gene and Cellular Therapies in
rameters are limited due to the small number of cases compared to female Cancer - Oncogen, Romania, 6 "Victor Babeş" University of Medicine
counterpart. The objective of this study is to evaluate clinical-pathological and Pharmacy, Timișoara, Romania, 7 Department of Pathology, "Victor
parameters in correlation with OS in male breast carcinoma. Babeș" University of Medicine and Pharmacy, Timișoara, Romania,
 Virchows Arch

8
Department of Pathology, Emergency County Hospital Timișoara, after a breast-conserving surgery with adjuvant radiation therapy for breast
Romania, 9 Department of Pathology, Emergency Clinical County carcinoma. Most tumours present as multifocal erythematouse plaques,
Hospital "Pius Brinzeu", Timisoara, Romania nodes, areas of ecchymosis or skin thickening. Morphologically the majority
of the RBAs are high grade with poor prognosis and high risk of local and
Background & Objectives: Breast cancer is commonly diagnosed over systemic recurrences.
50 years old, with only 5% of cases being under 40 years old. For the Methods: We present four cases of the RBA with emphasis on the clinical
latter cases we focused our study on the occurrence rate, topography, and morphological characteristics.
histological and immunohistochemical features. Results: Patients were aged 61 to 83 years old with invasive breast car-
Methods: We have conceived a 5 years retrospective study (2014-2018), cinoma, treated with breast-conserving surgery, radio-, chemo- and hor-
using the pathology department's database of "Pius Brânzeu" Emergency monal therapy. An interval between primary disease and development of
County Hospital Timisoara. During this time, 276 patients were diag- the RBA was five years in three of the cases and eleven years the fourth
nosed with primary breast carcinoma. Of these data we selected 25 pa- case. In all patients the RBA presented as a skin lesion with involvement
tients which were younger than 40 years old at the time of diagnosis. The of the underlying mammary tissue. IHC panel of CK AE1/AE3, CD31
inclusion criteria in study were: age, breast invasive carcinoma and IHC and CD34 were used for the final diagnosis.
performed. Conclusion: RBA is a serious long-term complication after breast-
Results: In our study, the average age of the patients diagnosed with conserving surgery and adjuvant therapy with high rates of local relapse.
breast carcinoma was 35.44 y.o. (9.09% of all cases). The annual rate of Its appearance may mimic reactive and benign conditions, which may
occurrence was 4-5 cases. The histological type for all 25 cases was lead to delay diagnosis. Complete clinical history and multidisciplinary
invasive carcinomas NST, G2 grade-16 cases (64%), G3-9 cases (36%) approach are of the great value for the final diagnosis.
with the immuneprofile: basal-like-12 cases (48%), luminal A-10 cases
(40%) and luminal B-2 cases (8%). Regarding the topography, the left
breast was involved in 12 cases (48%), the right-10 cases (40%) and 3 PS-01-066
bilaterally. The prognostic value of topoisomerase II-α for chemotherapy re-
Conclusion: The incidence of breast cancer in young women is steadily sponse and survival in breast cancer
in time. About topography, the most affected side is the left breast. Breast L. Zakhartseva1, M. Yanovytska1, Y. Zakhartsev2, M. Plodienko1
1
cancer in young women seems to be an aggressive malignancy with a National Medical Bohomolets University, Ukraine, 2 Kiev City
triple negative immune profile in most of the cases. Oncology Center, Ukraine

Background & Objectives: Topoisomerase II-α (topoIIα) protein is one of

PS-01-064 the intracellular targets for anthracycline-based therapy and is considered to
Frequency of breast-conserving surgery in breast cancer, in real-life have predictive value for antracycline-based chemotherapy regimens. Some
practice studies indicate the value of this marker for survival prediction. Available data
M. Urezkova1, A. Kudaybergenova1, E. Turkevich1, P. Krivorotko1 about topoIIα prognostic value remains controversial.
1
N.N. Petrov National Research Medical Center of Oncology, Russia Methods: 128 paraffin-embedded tumour samples from core biopsy
specimens with histologically confirmed breast cancer were evaluated
Background & Objectives: Surgery for breast cancer is one of the main by immunohistochemical analysis for topoIIα, estrogen and progesterone
therapies. Since 1991 ACSCC has recommended breast-conserving sur- receptors, Her2/neu and Ki-67. The average observation time period was
gery (BCS) for early-stage breast cancer. With BCS the criterion for 21 months. Those samples where preoperative biopsy was done were
optimally performed surgery is the clearance of the resection margins. evaluated (n=43) for chemotherapy response. Correlation regression anal-
The aim of this study determine the proportion of BCS and positive ysis (Pearson's correlation coefficient) was used to analyse the data.
margins in our hospital to compare with international findings. Results: Expression of topoIIα (evaluated as positive when higher than 20%)
Methods: The study included 3635 cases of breast cancer operated in our was detected in all molecular breast cancer subtypes. 76% was positive for
center in 2013-2018 years. topoIIα in luminal B subtype (n=50), 64% in Her2-enriched tumours (n=14),
Results: Total BCS was 1291 cases (39.1%). To compare with large studies 50% was positive in triple-negative subtype (n=16) and 23% in luminal A
Hwang investigated rate of BCS in 1990-2004 pointed 55% who received subtype (n=48). Relationship between proliferative index and topoIIα expres-
lumpectomy compare 45% for mastectomy; Norway study indicate 70% sion was high and statistically significant (p=0,000). No statistically signifi-
BCS in 1998-2009, Stefanie Corradini describing single-Institution life-prac- cant correlation between chemotherapy response, overall survival and expres-
tice in 1998-2014 detected 84.8% of patients treated with BCS and 15.2% sion of topoIIα was found.
with mastectomy. The positive resection margin (R1 resection) rate was de- Conclusion: Our data confirms that topoIIα expression is higher in ag-
termined in 5.8% of cases in our center. According to M. Morrow (2014) the gressive subtypes of breast cancer (associated with high Ki-67) and can
frequency of the positive margin reaches 12-22%. be interpreted as a kind of proliferative marker. It is associated with
Conclusion: The proportion of BCS and the frequency of R1 resection in luminal B, Her2new-enriched and triple negative subtypes. Probably in-
our study is significantly less than that described in international studies. The creased sensitivity to anthracycline-based chemotherapy among triple
reason of these differences may be different surgical activity of the operating negative and HER2-positive breast carcinomas is independent of expres-
surgeons, and should be important in determining the subsequent treatment. sion of topoisomerase IIα.

PS-01-065 PS-01-067
Radiation-associated breast angiosarcoma - case series The Immunogradient of CD8+ cell density in the tumour-stroma
B. Ilcheva1, S. Bachurska2, D. Tashkova2, A. Fakirova1, R. Hristoskova1 interface zone predicts overall survival of patients with hormone
1 receptor-positive invasive ductal breast carcinoma
Department of General and Clinical Pathology, Military Medical
Academy Sofia, Bulgaria, 2 Department of General and Clinical D. Zilenaite1,2, A. Rasmusson1,2, A. Nestarenkaite1,2, R. Augulis1,2,3, A.
Pathology, Medical University Plovdiv, Bulgaria Laurinaviciene1,2, V. Ostapenko4, T. Poskus5, A. Laurinavicius1,2
1
National Center of Pathology, affiliate of Vilnius University Hospital
Back grou nd & Ob jectives : R adi ati on -ass oc iat ed bre ast Santaros Clinics, Vilnius, Lithuania, 2 Department of Pathology, Forensic
angiosarcoma(RBA) is rare, aggressive soft-tissue neoplasma, which occurs Medicine and Pharmacology, Institute of Biomedical Sciences of the
Virchows Arch

Faculty of Medicine of Vilnius University, Lithuania 3 Institute of Quantitative analysis of optical density immuno- and hystochemical reactions
Biosciences, Life Sciences Centre, Vilnius University, Lithuania, 4 National was performed by Nikon Eclipse E 80 computer program.
Cancer Institute, Vilnius, Lithuania, 5 Institute of Clinical Medicine, Faculty Results: The increased expression of MECA-79 in the glycocalyx and
of Medicine, Vilnius University, Lithuania cytoplasm of the glandular and luminal epithelium was established in
group 1 compared with group 2. Similarly, the increase of cytoplasmic
Background & Objectives: Tumour infiltrating lymphocytes (TIL) expression the LeY was found in the epithelium and fucosylated struc-
are associated with better prognosis in triple-negative and HER2- tures with core type 2 (UEA-I staining positive) in the cytoplasm of the
positive breast cancer, and TIL assessment by digital image analysis glandular and luminal epithelium. On the contrary, a decrease expression
(DIA) has been successfully implemented in colorectal and other of α2-3-linked sialosides (MAL-II) in the glycocalyx of the luminal ep-
cancers. However, results in hormone receptor-positive breast can- ithelium was noted in group 1.
cer (HRBC) based on manual scoring remain contradictory. Here Conclusion: The presence of higher level MECA-79, specific for the
we used an automated DIA method to extract prognostic value of sulfated oligosachharides epitope of L-selectin ligands, and fucosylated
novel Immunogradient indicators in CD8+ cell density profiles in structures with core type 2 (containing Galβ1-4GlcNAc motif, including
HRBC. LeY) in mildsecretory phase was associated with a better pregnancy out-
Methods: Surgically excised HRBC samples from 102 patients were comes. This glycans may be considered as predictive markers of human
immunohistochemically stained for CD8, digitized and analysed by the uterine receptivity.
HALO™ platform. The DIA data was subsampled by a hexagonal grid
and explicit rules were then used to extract the tumour-stroma interface The study has been carried out within the State Contract №АААА-А18-
zone (IZ) and compute novel Immunogradient indicators from TIL den- 118053190022-8.
sity profiles across the IZ. The prognostic value was evaluated by survival
analysis.
Results: The IZ Immunogradient indicators (mean CD8+ density in the PS-02-004
tumour aspect of the IZ, Immunodrop, Centre of Mass) allowed prognostic Unravelling genetic alterations in endometrioid endometrial cancer
stratification of patients in univariate analyses (hazard ratios: 0.21 (p=0.0002), and correlation with molecular subgroups and immunologic tumour
2.79 (p=0.0140), and 0.28 (p=0.0044), respectively). The best and indepen- microenvironment
dent indicator of better OS by multiple Cox regression model (hazard ratio: B. Willvonseder1, K. Steiger2, H. Bronger3, G. Keller1, W. Weichert4, A.
0.23 (p=0.0007)) was an aggregated Immunogradient factor (AF), obtained Noske1, N. Pfarr5, M. Boxberg5
by the sum of two factor scores (CD8+ density and “gradient towards the 1
Institute of Pathology of the Technical University of Munich, Germany,
2
tumour”). Remarkably, the AF revealed a striking drop of patients’ survival Institute of Pathology, TUM School of Medicine, Technical University
probability 5 years after surgery. of Munich, Germany, 3 Department of Obstetrics and Gynaecology,
Conclusion: The Immunogradient indicator for CD8+ cell density is an Technical University of Munich, Germany, 4 Technical University of
independent predictor of better OS in HRBC patients with the particular Munich, School of Medicine, Institute of Pathology, Germany, 5
diversion of OS 5 years after the surgery. Institute of Pathology, Technical University Munich, Germany

This research was funded by the European Social Fund according to the Background & Objectives: Advanced endometrioid endometrial cancer
activity “Improvement of researchers’ qualification by implementing (EC) carries a poor prognosis with immune-checkpoint blockage (ICB)
world-class R&D projects”, No. 09.3.3-LMT-K-712. emerging as therapeutic option. Antigen-presentation (AP), interferon-
signalling (INF) and immune-checkpoint receptors (IC) have been associated
with tumour immunology and ICB-response. Developing a next-generation-
Sunday, 8 September 2019, 09:30 - 10:30, Agora 3 sequencing (NGS) panel, we determined molecular alterations in the above
PS-02 | Gynaecological Pathology named immunologically relevant pathways and analysed correlations with
EC molecular subgroups and immunologic microenvironment.
Methods: We investigated baseline molecular parameters (mismatch repair,
PS-02-003
TP53, ARID1A, PTEN, estrogen receptor) by immunohistochemistry/NGS
Glycans expression in endometrium of infertile patients
in n=50 therapy-naïve EC. We quantified tumour-infiltrating lymphocytes
A. Asaturova1, N. Abdurakhmanova1, G. Kulikova1, M. Ziganshina1, N.
(Pan-T-cells; T-killer-cells; regulatory T-cells; PD-1+ cells) and PD-L1 in
Faizullina1, A. Shchegolev1, G. Sukhikh1
1 tumour und immune cells. Our NGS panel contained n=54 genes of AP
FSBI 'National Center for Obstetrics, Gynaecology and Perinatology
(e.g. HLA-A), AP machinery (e.g. B2M), INF (e.g. JAK2) and IC (e.g.
named after V.I.Kulakov' Ministry of Healthcare Russian Federation,
PD-L1).
Russia
Results: Mutations in investigated genes were frequent (n=11 INF, n=10
AP machinery, etc). TP53-mutation and immunologic mutations were mu-
Background & Objectives: Significant changes in the endometrial
tually exclusive, mutations in immunologic pathways were exclusively
glycome, associated with an increase of expression of highly gly-
detected in PTEN-mutant EC (p<0.03). Presence and high number of mu-
cosylated proteins that having terminal sialic acid and fucose res-
tations were more frequent in poorly differentiated EC (p<0.05). High PD-
idues, occur during the window of implantation. Since sialoglycans
L1-expression in tumour and immune cells was correlated with presence
and sulfated fucosylated glycoconjugates are key molecules medi-
and high number of immunologic mutations as well as high density Pan-T-
ating cell-cell contacts, disruption of their expression may be the
cell and T-Killer-cell infiltrate (p<0.05) irrespective of affected pathway.
reason for the lack of IVF. The aim was to evaluate the expression
Conclusion: Molecular alterations in immunologic pathways were fre-
of sialo-, and sulfated fucosylated glycans in the endometrium of
quent and exclusively detected in PTEN-mutant EC. TP53-mutation and
patients with different reproductive outcomes in IVF programs.
immunologic mutations were mutually exclusive. Mutations in immuno-
Methods: A histochemical and immunohistochemical analysis of paraffin-
logic pathways were closely correlated with a highly immunogenic sub-
embedded endometrial samples was performed using an UEA-I, MAL-II
group of EC characterised by high PD-L1 expression and high density T-
lectins (Vector Labs) and anti-LeY (Abcam), anti-PNAd (MECA-79) (BD
cell-infiltrate. This subgroup may potentially be predictive for ICB-
Pharmingen) monoclonal antibodies. We included 34 patients with tubal
response and might be further investigated in biomarker studies.
factors of infertility, which were divided into two groups: women with preg-
nancy after IVF (group 1) and patients who failed an IVF cycle (group 2).
Funding by Else-Kröner Fresenius Stiftung (to Melanie Boxberg).
 Virchows Arch

PS-02-005 underwent conservative surgery, including cystectomy (n=24|24.8%)

Ovarian immature teratoma: characteristics, treatment and out- and unilateral salpingo-oophorectomy (n=54|53.5%). Twenty-two
comes of 20 women (1994-2012) (21.8%) had chemotherapy and one had radiotherapy. Six (5.9%) patients
D. Chiba1, N. Abdessayed2, S. Chaieb2, A. Baccouche2, T. Zahmoul3, S. relapsed and four (3.9%) died of disease.
Yacoub2, B. Sriha2, M. Mokni2 Conclusion: Paediatric gynaecological lesions comprise a wide variety of
1
Department of Pathology Farhat Hached Hospital, Tunisia, 2 Farhat rare histological tumour subtypes, warranting evaluation by an experi-
Hached Hospital, Tunisia, 3 Cancer Registry of the Tunisian Center, enced pathologist. Conservative management of gynaecological tumours
Tunisia in the paediatric setting, with fertility sparing surgery and limited use of
adjuvant therapies, allows high recurrence-free and overall survival with
Background & Objectives: Immature Teratomas (IT) of the ovary are a decreased later morbidities.
type of germ cell cancer that accounts for less than 3% of malignant
ovarian cancer. These tumours are usually diagnosed in children and
young women ranging from 10 to 30 years and have a good prognosis. PS-02-007
The aim of this study is to evaluate clinical and pathologic characteristics Placental attachment pathology (PAP) in women with uterus scar
and treatment outcome in women diagnosed with ovarian immature and undifferentiated connective tissue dysplasia (UCTD)
teratoma. T. Demura1, E. Kogan1
1
Methods: Sousse registry cancer center database was used to iden- First Moscow State Medical University (Sechenov University), Russia
tify women diagnosed with an immature teratoma from 1994–2012.
Patient’s clinical presentation, operative and chemotherapy details Background & Objectives: The morphological substrate of UCTD is
were included in a database. Follow up details regarding recurrence impaired tissue repair with scar formation with further development of its
and management and future outcomes were also noted. Overall sur- disorganization (Demura et.al. 2012).
vival was calculated from the date of registration to last follow up. The aim: to study morphological substrate and molecular aspects of the
We identified a total of 20 women with Immature Teratoma. The median PAP in women with a scar on the uterus and UCTD.
age at diagnosis was 28 years (range: 14–63 years). Methods: 10 removed uteri and placenta from women with different
Results: Pain was the predominant symptom and abdominal mass variants of the PAP, the postpartum period of which was complicated
was the commonest clinical presentation. Sixtee (80%) presented by bleeding or endometritis: 7 patients with UCTD and 3 - without.
with stage I disease, 2(10%) with stage II, and 2 with indeterminate Morphological and immunohistochemical study were performed.
stage. 11 (55%) of the tumours were found to be grade 1,6 (30%) Results: In patients with UCTD, ingrowth of the chorionic villi was
grade2, and 3(10%) grade3. Initial management was surgical for all found in the area of the old uterine scar (n=7), in which mucoid swelling
patients: 14 (70%) unilateral oophorectomy, 2 (10%) cystectomy on- and fibrinoid necrosis were detected. There were 8 cases of Placenta
ly and 5(25%) bilateral oophorectomy with hysterectomy. Eleven accreta (5 cases with UCTD, 3 cases without), 2 cases of Placenta increta
(55%) patients received adjuvant-chemotherapy. Only one clinical with UCTD. The area of the placental site in UCTD contains collagens I
stage II/Grade3 patient who received adjuvant-chemotherapy devel- and III, with a slight predominance of the latter. A significant increase in
oped a recurrence and underwent a second surgery. the MMP-1, 2 was found in UCTD compared with the control (p <0.05),
Conclusion: The median follow up was 5 years. All (100%) patients were while expression of TIMP-1 was reduced (p <0.05). PAP in women with
alive after 5 years. UCTD develops in the area of the scar formed after operation
Most patients present with early-stage disease, are managed with fertility Conclusion: In women with UCTD uterine scar tissue has abnormal ratio
sparing surgery associated or no to chemotherapy and have an excellent of collagens, MMPs and TIMP, that facilitates the invasion of the chori-
prognosis. However, grade 2 or 3 tumours are associated with a greater onic villi into the scar, resulting in the latter becoming and the source of
chance of recurrence that can be fatal. bleeding and endometritis.

PS-02-006 PS-02-008
Gynaecological tumours in the paediatric age: a clinico-pathological A clinicopathologic study of mesonephric-like adenocarcinoma of the
study female genital tract
J. Costa1, S. Alves2, F. Silva1, F. Leite3, C. Bartosch1 M. Fukunaga1
1
Department of Pathology IPOP, Portugal, 2 Department of Oncology 1
Department of Pathology, Shin-yurigaoka General Hospital, Japan
IPOP, Portugal, 3 Department of Paediatrics, IPO-Porto, Portugal
Background & Objectives: Mesonephric adenocarcinomas (MAs) are
Background & Objectives: Gynaecological tumours and tumour-like rare neoplasms of the female genital tract that primarily arise in the
lesions in children and adolescents are rare, however the potential phys- cervix, and are defined as adenocarcinomas arising from mesoneph-
ical, psychiatric and social sequelae of these diagnoses may be ric remnants based on the WHO classification. Adenocarcinomas of
devastating. the uterine corpus and ovary characterised by morphological and
Methods: Observational retrospective cohort study describing the immunophenotypical similarities with MA have been reported, and
gynaecological tumours and tumour-like lesions diagnosed in pa- these tumours have been termed mesonephric-like adenocarcinoma
tients aged 0-19 years at Portuguese Oncology Institute of Porto (MLA).
between 2000 and 2018. In total, 101 patients were included, com- Object is to clarify histologic diversity, histogenesis and biologic behav-
prising 98 (79.7%) tumours and 25 (20.3%) tumour-like lesions. iour of MLAs of the ovary and endometrium.
Results: Benign tumours: 45 (45.9%); borderline: 22 (22.5%); malig- Methods: Nine cases of MLA were clinicopathologically and
nant: 31(31.6%). Most common sites: ovary (86.2%) and cervix (5.7%). immunohistochemically studied.
Most common histologic types: germ cell tumours (50.0%) and epithelial Results: There were five adenocarcinomas (ACs) and four
tumours (38.8%). Tumour-like lesions: follicular cysts (n=9|39.1%), ad- carcinosarcomatous ACs (CSACs). ACs were found in the endometrium
nexal torsions (n=7|30.4%) and endometriosis (n=4|17.4). Frequency of (2) and ovary (3). CSACs involved the ovary (2) and the endometrium
lesions increased with age. Age of diagnosis for epithelial tumours was (2). ACs exhibited glandular, retiform, and solid proliferations. Two ACs
higher compared to germ cell tumours: 17 (6) vs.14 (18) years and one CSACS had mixed serous and endometrioid adenocarcinomas.
(median(range)), p=0.001. The majority of patients(n=91|90.9%) One ovarian AC was associated with endometriosis. All tumours were
Virchows Arch

positive for CD10 and calretinin. Three patients with CSAC died of at the time of initial diagnosis who will have worse prognosis in order to
disease. No patients with AC died of disease choose the appropriate treatment; so many studies have been maintaining
Conclusion: Diverse histological patterns were observed and no meso- to detect new prognostic markers like ours.
nephric remnants were found any case. Some MLAs may be considered Methods: 102 females who underwent histerectomy with bilateral
as Mullerian adenocarcinomas with mesonephric differentiation. The salpingo-oophorectomy and diagnosed as EEC histopathologically were
possibility of MLA should be considered when encountering an evaluated retrospectively. TROP2, a transmembrane receptor glycopro-
unusual-appearing carcinoma, malignant mixed tumour, or even tein coded by the tumour-associated calcium signal transducer 2
endometrioid adenocarcinoma. CSACs may be more aggressive than ( TA C S T D 2 ) g e n e w a s a p p l i e d t o t h e t u m o u r a l s e c t i o n s
ACs. immunohistochemically and the staining rates were compared with the
current prognostic factors.
Results: TROP2 overexpression was statistically correlated with high
PS-02-009 nuclear and architectural grades, deep myometrial invasion, more lymph
Malignant struma ovarii: a case of columnar variant of papillary node metastasis and the presence of vascular invasion(p<0.05).
thyroid carcinoma Conclusion: This study exposed that TROP2 overexpression is correlat-
A. González Antelo1, K. Romero Figueroa1, C. Sánchez Cendra2, V. ed with worse prognosis as the parameters studied are classic prognostic
Peiro Valgañón3, J. Calzas Rodríguez2, R. Cardozo Rocabado1, î parameters. TROP2 overexpression has been considered in various types
Castaño Pascual1, N. Cozar García1 of cancers including thyroidal, biliary, oral, pancreatic, laryngeal, naso-
1
Department of Pathology, University Hospital of Fuenlabrada, Madrid, pharyngeal, ovarian, gastric cancers, breast, lung, bladder, prostate, gall-
Spain, 2 Department of Medical Oncology, University Hospital of bladder cancer.
Fuenlabrada, Madrid, Spain, 3 Department of Nuclear Medicine,
University Hospital of Fuenlabrada, Madrid, Spain
PS-02-014
Background & Objectives: Malignant struma ovarii is an infrequent and Tumour budding in cervical carcinoma: associations with some clin-
challenging diagnosis. We submit a case of a columnar cell variant of ical and pathological factors
papillary thyroid carcinoma in struma ovarii, previously diagnosed as T. Ivković-Kapicl1, N. Stanulović1, A. Mandić1, Z. Nikin1
1
endometrial adenocarcinoma. Oncology Institute of Vojvodina, Serbia
Methods: A 57-year old patient presented with a history of
hypermenorrhea. Echography images revealed a 4-cm benign cyst in Background & Objectives: Tumour budding is recognized as an impor-
her right ovary. She was lost to follow-up and, 10 years later, the lesion tant independent prognostic factor in colorectal carcinoma. The aim of
showed hyperrefringence, left ovary was affected and there were multiple this was to evaluate the grade of tumour budding in patients with cervical
adherences to the uterus and rectum. A hysterectomy and bilateral carcinomas and any associations with other clinical and pathological
adnexectomy were decided. features
Results: We received a left ovary with a ruptured capsule, occupied by a Methods: We observed pathohistological data of 91 patients (mean age:
white, cystic lesion with necrotic and solid areas, and a fragmented right 53,8 years), who underwent radical hysterectomy and pelvic lymphatic
mass. An infiltrative hypercellular neoplasm with pseudoglandular pat- dissection in the Oncology Institute of Vojvodina, between January 2010
tern and some groups of fine papillae were found. It exhibited a and December 2018.
pseudostratified epithelium formed by cells of little cytoplasm, elongated Results: 84 (85,07%) patients were diagnosed with squamous, 5
and hyperchromatic nuclei and focal subnuclear vacuolization. These (13,43%) with adeno- and 2 (1,49) % with adenosquamous histological
findings were interpreted as an endometrial adenocarcinoma, type of cervical carcinoma. According to tumour histological grade, pa-
endometrioid type. Despite adjuvant chemotherapy, the patient returned tients were divided in 3 categories: G1 (15,3%), G2 (62,6%) and G3
with peritoneal carcinomatosis and cytoreductive surgery was performed. (21,9%). Average diameter of the tumour was 25mm (81,6%< 4cm and
The biopsy revealed a focus of classic papillary carcinoma. As both 18,4% > 4cm). Metastasis in lymph nodes were present in 30 (32,9%)
previous and current lesions tested positive for TTF-1, PAX-8 and thyro- cases. Tumour budding was evaluated in a invasive front of the tumour.
globulin, our final diagnosis was a columnar cell variant of papillary Based on the number of bud counts/10 HPF, 3 groups were formed: 1- no
thyroid carcinoma in struma ovarii. No synchronic tumours were found budding (35,1%), 2- less than 15 buds (32,9%), and 3- more than 15 buds
and the carcinoma was resistant to radioactive iodine therapy. (37,3%). We determined positive correlation between tumour budding
Conclusion: To the best of our knowledge, this is the first reported case of grade and histological grade of the tumour (p=0,04), and also the diameter
a columnar variant of papillary thyroid carcinoma in struma ovarii, a of the tumour (p=0,05). Futhermore, we obsereved presence of
neoplasia whose early diagnosis is extremely difficult. lymphovascular and perineural invasion and determined significant cor-
relation between tumour bud count and those parameters (p=0,02).
Conclusion: As a quantitative measure of cancer cell dissociation, tu-
PS-02-013 mour budding is associated with established poor prognostic factors in
TROP2 expression in endometrioid type endometrial carcinoma and cervical carcinoma and therefore sholud be considered as one of them.
correlation with the prognostic factors
O. Ilhan Celik1, S.Y. Celik1
1
Mugla Sitki Kocman University, Faculty of Medicine, Department of PS-02-015
Pathology, Turkey Power of cytology in women with HPV 16 or 18 positivity: is direct
referral to colposcopy sufficient?
Background & Objectives: Endometrioid type (EEC) endometrial car- K.E. Kaçar1, I.E. Seven1, F. Eren1
1
cinoma is the most common malignancy of the female genital tract in Marmara University, Turkey
developed countries. The incidence and the death rates have been increas-
ing in the recent decades. It is known that the prognosis of EEC greatly Background & Objectives: The positivity of HPV 16 or 18 in women is
depends on the grade and the stage and has good prognosis when diag- associated with increased risk of cervical intraepithelial lesion and malig-
nosed in early stages. However in some patients the disease recur in a nancy compared to other HPV types. In primary hrHPV screening guide-
short time after the treatment. In these recurrent diseases the prognosis lines, referral to direct colposcopy is recommeded for women with HPV
worsen and the survivals shorten. So it is important to predict the patients 16 or 18 positive test results.
 Virchows Arch

The aim of this study is to determine the correlation between the results of Conclusion: Study ascertain the expression of kisspeptin, its receptor in
cervical cytology and colposcopic biopsy applied to HPV 16 or 18 pos- ontogenesis of human ovary.
itive women.
Methods: Women who were screened by both hrHPV and cervical cy-
tology between January 2014 -December 2018 were evaluated. Among PS-02-017
them, HPV 16 and 18 positive 101 patients who underwent colposcopy Expression of TMC6 protein in ovarian carcinomas predicts pa-
were included in the study. tient's response to chemotherapy
Results: The cytology results of 48 of 101 women were NILM (negative M. Manai1, R. Doghri2, G. Sahraoui3, P. Finetti4, M. Manai5, F. Bertucci4,
for intraepithelial lesions or malignancies), 3 of them were inadequate. K. Mrad2, M. Driss6, L. Charfi2
1
Although colposcopic biopsy results of 38 (79%) of them were in corre- Institute Salah Azaiez, Tunisia, 2 Department of Pathology, Salah
lation with cytology, in 10 (21%) of them a cervical pathology was diag- Azaiez Institute, Tunisia, 3 Institute Salah Azaiez, Tunisia, 4 Institute
nosed [ CIN1 (n:5), CIN2 or CIN3 (n: 4) and CIN can not be graded due Paoli Calmettes, France, 5 Facultè des Sciences de Tunis, Tunisia,
6
to inadequate biopsy (n:1) ]. Cytology slides of these 10 cases were re- Department of Pathology, Salah Azaïez Institute, Tunisia
evaluated. Interpretation error was detected in 4 of them and they were
upgraded to ASC-US, ASC-H or SIL category. As a result, 6 (5.9%) Background & Objectives: Ovarian Carcinoma (OC) is the most lethal
patients would be misdiagnosed if they would have evaluated with smear gynaecological cancer. Identification of new therapeutic targets is crucial.
only. 50 of 101 women had positive cytology results (ASC-US, LSIL, Transmembrane channel like 6 (TMC6) expression found to be implicat-
ASC-H or HSIL). Colposcopic biopsy diagnosis of 11 (22%) women ed in cancer aggressiveness.
were discordant with cytology and reported as non-neoplastic. The cytol- Methods: We measured TMC6 protein expression in normal ovarian and
ogy results of these cases were ASC-US in (n:4), LSIL (n:3), ASC-H OC samples and searched for correlations with clinicopathological fea-
(n:2) and HSIL (n:2). Both the cytology and biopsy slides were re- tures. TMC6 status was evaluated by immunohistochemistry in 50 tu-
evaluated and the results were confirmed. As a result, 11 (10.9 %) patients mour samples and 20 normal ovarian samples. We compared TMC6
would be misdiagnosed if they would have evaluated with colposcopic expression in normal versus cancer samples and with clinicopathological
biopsy only. features.
Conclusion: Cervical cancer screening methods are one of the few Results: In tumour samples, the staining was observed mainly in epithe-
screening methods that are thought to reduce the incidence and mortality lial cells and to a lesser degree in stroma cells (p=1.27E-02, Fisher’s exact
of invasive cancer and have proven effective in this respect. Therefore, it test). TMC6 was overexpressed in 66% of OC samples versus 26% in
is important to perform this screening with the most appropriate method. normal samples (p=1.40E-07, Fisher’s exact test). TMC6 expression was
According to the results of our study, colposcopic biopsy alone have a correlated to the menopausal status (p=4.20E-02, Fisher’s exact test) and
higher rate of missing a cervical pathology when compared to cytology to sensibility to chemotherapy (p=3.31E-03, Fisher’s exact test).
alone. Therefore in women with HPV 16 or 18 positivity, cytology Conclusion: Epithelial TMC6 overexpression in tumours might contrib-
screening should not be ommitted before referral to colposcopy. ute to a good response to chemotherapy. TMC6 can represent a potential
therapeutic target for OC to improve the response to chemotherapy.

PS-02-016
Protein expression of KISS1 and KISS1R in human ovary in differ- PS-02-019
ent stages of ontogenesis Carboxypeptidase-M as a novel marker of endometrial cancer
A. Drobintseva1,2, J. Krylova1,3, V. Polyakova4, I. Kvetnoy4 B. Nagy1
1 1
D.O. Ott. Research Institute of Obstetrics, Gynaecology and University of Szeged, Department of Pathology, Hungary
Reproductology, Russia, 2 St. Petersburg State Paediatric Medical
University, Russia, 3 Pavlov First Saint Petersburg State Medical University, Background & Objectives: The substantial morphological overlapping
Russia, 4 Ott`s Institute of Obstetrics, Gynaecology and Reproductology, between endocervical and endometrial cancers is a well-known daily
Russia diagnostic issue. With routine tissue sampling the H&E based morpho-
logical findings rarely enough to make a proper diagnosis. Therapeutic
Background & Objectives: Kisspeptins regulate the hypothalamic- approaches necessitate attempts to distinguish these two very similar
pituitary-gonadal axis, the most important function of them is to trigger tumours of the uterus. Immunohistochemistry profiling is based on
the onset of puberty. Studies of kisspetins expression in ovarian tissue are Vimentin, CEA, p16 and hormone receptor positivity. Using panel of
most often devoted to the reproductive period, but there is no data on what reactions tumours usually identifiable, but there are cases that remain
time of prenatal development the KISS1/KISS1R system begins and fin- equivocal. An emerging need of a sensitive and/or specific marker is
ish functioning. Aim. To investigation of the protein expression of undisputable.
kisspeptin and its receptor in human ovarian tissue at different stages of Methods: 50 consecutive tissue samples of curettage and hysterectomy
ontogenesis. specimens were examined. Epithelial cancer’s immunohistochemical pat-
Methods: The material for the study was archival autopsy samples of tern of Vimentin, CEA, progesterone receptor, p16 and Carboxypeptidase
ovaries from 10 foetuses (22-42 weeks), 2- children 1–10 years old (n=5), M (CPM) was investigated. High throughput method of tissue microarray
3- children 11–15 years old (n=5), 4 - reproductive age 19-40 years old was used. Observation of the expression pattern and strength were
(n=23), 5 - premenopausal women 46-55 years old (n=11), 6- postmen- registered.
opausal women 56-82 years old (n= 9). For IHC staining were used Results: Endometrial and endocervical cancers express wide range of
antibodies to Kiss1 (1:150, Abcam), Kiss1R (1:350, Abcam). progesterone receptor and p16. Vimentin is a sensitive but not spe-
Results: The KISS1/KISS1R system begins to function during foetal cific marker of endometrial cancer, while CEA suggests endocervical
development, and as early as the 22nd week of gestation, a positive origin. Frank membranous expression of CPM was detected only in
reaction was recorded in the ovarian tissue. At reproductive age, the endometrial cancers, and all endometrial cancer expressed CPM,
expression of kisspeptins remains at a consistently high level, during respectively.
menopause, the expression of kisspeptins in the ovaries reaches its peak, Conclusion: Strong membranous Carboxypeptidase-M expression is a
which may be due to a compensatory mechanism for reducing the syn- valuable immunohistochemical marker of epithelial endometrial cancer
thesis of ovarian estrogen. In postmenopausal period minimum values independently from the grade or morphological type. It is also a reliable
were fixed. marker to differentiate endometrial and endocervical cancers.
Virchows Arch

PS-02-020 with or without IUGR were peculiar to cytoplasmic staining, while mod-
Histoprognostic factors predicting lymph node metastasis in endome- erate preeclampsia and full-term pregnancy was characterised by mem-
trial cancer brane staining predominantly. It can be assumed severity of preeclampsia
R. Narjess1, N. Boujelbene2, M. Driss3, L. Charfi2, H. Arbi3, K. Mrad2, R. correlated to loss of TLR8 membrane expression of syncytiotrophoblast.
Doghri4 Conclusion: Disturbances of TLR8 in placental tissue may be an impor-
1
Institute of carcinology Salah Azaiz Tunis, Tunisia, 2 Department of tant role in the genesis of preeclampsia.
Pathology, Salah Azaiez Institute, Tunisia, 3 Department of Pathology,
Salah Azaïez Institute, Tunisia, 4 Department of Pathology, Salah Azaïez Supported by the Grant of the President for leading scientific schools
Institute, Tunis, Tunisia (NS-4566.2018.7, Agreement 075-02-2018-519).

Background & Objectives: Endometrial cancer (EC) is the most com-

mon malignancy of the female reproductive tract. Lymph node metastasis PS-02-022
(LNM) is one of the most important prognostic factors for EC. We aimed The placental and umbilical cord lesions in the genesis of foetal
to evaluate the value of pathological characteristics in predicting the risk hypoxia
of LNM in women with EC. N. Nizyaeva1, A.M. Prikhodko1, A.V. Evgrafova1, O.V. Tysyachny1,
Methods: A single centre retrospective analysis was conducted in pa- D.A. Shuklina1, O.R. Baev1
1
tients with EC who underwent systematic lymphadenectomy. V.I.Kulakov National Research Center for Obstetrics, Gynaecology and
Clinicopathologic data including age, type of surgical procedure, tumour Perinatology of Ministry of Healthcare of the Russian Federation,
histotype, tumour size, grade, count of lymph nodes removed, depth of Moscow, Russia
myometrial invasion, cervical involvement and LN involvement were
extracted from patient Institutional database. Chi-square and Fisher’s ex- Background & Objectives: Was to evaluate the placental villous tree
act tests were used for univariate analyses when appropriate. Variables and umbilical cord lesions in the genesis of foetal hypoxia.
with a p value <0.05 in the univariate analysis were included into a Methods: Two groups women with foetal hypoxia consisted of 26
multivariate logistic regression analysis. (PH>7.05 - 7.15 (group I) and 32 patients (PH<7.0 (group II). Control
Results: A total of 68 patients were included. The median age was 62 group included 10 (PH > 7.15) women with uncomplicated full-term
years (range from 38 to 81 years). In univariate analysis, tumour size ≥ pregnancy (UP) and labor. Нistological examination (hem&eosin) were
50mm, non-endometrioid histologic type, presence of cervical involve- performed on the paraffin-embedded placenta slices, received after cesar-
ment and lymphovascular invasion were found associated with LNM. ean section at 38-40 gestation weeks.
However, lymphovascular invasion and histologic type were the only Results: Changes in the umbilical cord included: thinning umbilical cord,
independent variable that predict LNM in multivariate analysis (p=0.01 absolute shortness length, marginal or membrane attachment, decreased or
and <0.0001 respectively). Deep (≥ 50%) myometrial invasion, grade 2-3 increased spiral turns (coiling/length index less than 0,1, more than 0,45,
and total lymph nodes removed were not associated with LNM. respectively); sludges and microthrombi in umbilical blood vessels, hemor-
Conclusion: The current study demonstrates that lymphovascular inva- rhages & hematomas of Wharton's jelly. In the groups of foetal hypoxia
sion and non-endometrioid histologic type in EC increases the probability these changes were present significantly more often than in UP(p<0.05).
of LNM. These features were the result of the acute hypoxia predominantly. In pla-
cental samples of group II, villous tree lesions reflected specific morpholog-
ical sings for chronic hypoxia: old infarctions of the villous tree, increased
PS-02-021 number of syncytial knots, vascular branching angiogenesis, fibrosis of the
TLR8 expression in placental samples in cases of preeclampsia and in villous stroma(p<0.05). In group I villous tree features were similar to UP.
intrauterine foetus growth restriction Conclusion: According to FSL data revealed in the group of foetal hypoxia
N. Nizyaeva1, E.Y. Amiraslsnov1, N.A. Lomova1, N.A. Savelyeva1, (PH<7.0) umbilical cord changes were associated with blood supply distur-
M.N. Nagovitsyna1, A.I. Shchegolev1 bances leading to acute hypoxia. The significant umbilical cord and villus
1
V.I.Kulakov National Research Center for Obstetrics, Gynaecology and tree lesions were observed in severe hypoxia group I (PH>7.05 - 7.15),
Perinatology of Ministry of Healthcare of the Russian Federation, interpreted as the combination of acute and chronic hypoxia manifestations.
Moscow, Russia

Background & Objectives: was to study TLR8 in placenta samples in PS-02-023

cases of preeclampsia (PE) and intrauterine growth restriction (IUGR). Intraoperative Pathologic Ultrastaging of Sentinel Lymph Node
Methods: We performed histological (hem&eosin) and immunohisto- (InSLNpU) in endometrial carcinoma. Study on 67 patients
chemistry studies on the paraffin-embedded slices of placenta, taking after A. Pesci1, G. Bogina1, M. Ceccaroni2, E. Munari1, L. Bortesi1, G.
cesarean section, 26-39 gestation weeks, using TLR8 primary polyclonal Querzoli1, G. Zamboni3
1
antibodies (1:250; GenTex,USA). Groups with PE included 15 women Pathology-IRCCS Ospedale Sacro Cuore-Don Calabria, Italy,
2
with severe PE and 8–with moderate PE, 6 samples–with PE complicated Gynaecology-IRCCS Ospedale Sacro Cuore- Don Calabria, Italy,
3
IUGR. Control groups included 10 women with full-term uncomplicated Pathology-IRCCS Ospedale Sacro Cuore-Don Calabria, Università di
pregnancy (UP). The intensity of immunohistochemical reaction was esti- Verona, Italy
mated by means of microscope imaging software NIS-Elements.
Results: TlR8 demonstrated more intensive expression in Background & Objectives: Sentinel lymph node (SLN) has been intro-
syncytiotrophoblast in cases of severe PE complicated by IUGR duced to obtain information about the LN status in endometrial carcinoma
(70.97+10.7 and 76.32+21.5, respectively;р<0,01). In samples of full- (EC) since systemic lymphadenectomy (SLAD) is still controversial due
term pregnancy, membrane and cytoplasmic staining was minimal to morbidity and insignificant survival effect.
(18.39+8.3 and 15.09+5.9, respectively; р<0,01). However, in severe Our aim was to evaluate the accuracy and feasibility of intraoperative path-
preeclampsia without IUGR in syncytiotrophoblast there was decreased ologic ultrastaging of sentinel LN (InSLNpU) in a cohort of pts with EC.
membrane staining. At the same time, with moderate PE, membrane Methods: 72 of the 109 EC diagnosed in the period 2016-2018
staining was higher compared to cytoplasmic (43.4+15.8 and 32.03+ underwent SLN procedure (67 Endometrioid: 6G3, 7G2, 54G1, 2Clear
16.2), than in UP (18,39+8,3 и 15,09+5,9, respectively; p<0.01). Cell, 2Serous, 1Mixed). 67/72 cases had one or more LNS (range 1-8); in
Increased TLR8 expression in placental samples in severe preeclampsia 5 cases no SLN was recognized. SLNs were bidissected, 1H&E and 1
 Virchows Arch

unstained slide per level, 5 levels at 150 μm apart. Positive-SLNs were histopathological response in the ovary and omental metastases in ad-
classified as: micromets (μ:0.2-2 mm) and macromets (m: > 2 mm). vanced stage HGSOC patients with and without BRCA1 mutations treat-
Positive-SLNs, on frozen, had 1 H&E for permanent. Negative-SLNs ed by platinum-containing neoadjuvant chemotherapy (NACT).
had 1 H&E, Keratin ICH and 1 unstained slide per 3 levels at 200 μm Methods: 85 women (31 BRCA1 carriers and 54 sporadic cases) with
apart for permanent. HGSOC, who underwent optimal interval debulking and had follow-up
Results: Only one case had positive-InSLNpU (m); 66/67 was nega- data, were included in the study. Histopathological chemotherapy re-
tive. The permanent sections confirmed the diagnosis in 62/66 cases sponse score (CRS) was assessed according to [Böhm et al., 2015].
(93.9%): 1 m, and 3 low-volume LN metastasis (1μ, and 2 ITC). 23/ Omental lesions were evaluated in 67 cases (22 BRCA1-associated and
67 pts examined with InSLNpU had SLAD; 2 pts presented with 45 sporadic tumours) where the initial presence of omental metastases
mets, one with positive-InSLNpU and 1 negative-InSLNpU. was confirmed. Disease-free interval (DFI) was defined as the time be-
Among the 21 cases SLAD negative, 2 were positive on permanent tween the end of adjuvant therapy and first relapse.
SLNpU (1 ITC, 1 μ). Results: BRCA1-associated HGSOC were characterised by a higher fre-
Conclusion: InSLNpU is reliable and correlate with final pathologic quency of CRS2-3 as compared to sporadic cases [25/31 (81%) vs. 31/54
assessment. Only 1/66 negative-InSLNpU showed metastasis (m). 3/66 (57%), p = 0.03]. CRS in ovary did not associate with the DFI either in
showed low-volume LN metastasis, whose clinical significance is still BRCA1-induced or in sporadic cases. CRS3 in omentum predicted longer
controversial. InSLNpU could be applied on routine when necessary. DFI in BRCA1-associated but not in BRCA1-wild-type HGSOC [p =
0.03 and p = 0.08 for BRCA1 carriers and sporadic cases, respectively;
Kruskal-Wallis test].
PS-02-024 Conclusion: Prognostic value of CRS may differ between hereditary and
CD8 T lymphocytes and FOXP3 T regulatory lymphocytes in sporadic HGSOC.
patients with high-grade squamous intraepithelial lesions
M. Pukis1,2, A. Mitildzans3,4, D. Rezeberga4,5, S. Isajevs2,1 This work was supported by the Russian Science Foundation (grant 19-
1
Centre of Pathology, Riga East University Hospital, Latvia, 15-00168).
2
Department of Pathology, University of Latvia, Faculty of Medicine,
Riga, Latvia, 3 Department of Oncology, Riga East University Hospital,
Latvia, 4 Department of Gynaecology and Obstetrics, Riga Stradins PS-02-026
University, Latvia, 5 Department of Gynaecology, Riga East University Clinicopathologic features of mismatch repair (MMR) protein-
Hospital, Latvia deficient endometrial carcinomas, tested by immunohistochemistry:
a single Institutional experience
Background & Objectives: Regulatory (FOXP3+) T cells (Tregs) com- B. Rekhi1, S. Menon1, K. Deodhar1
1
prise a subpopulation of CD4+ T cells that suppress autoreactive immune Department of Pathology, Tata Memorial Hospital, Mumbai, India
cells, thereby protecting organs and tissues from autoimmunity. Novel
therapeutic strategies for cervical cancer and squamous intraepithelial Background & Objectives: Few studies have described certain clinico-
lesions (SIL) focus on immune-modulatory and cancer vaccination pathologic features in mismatch repair protein (MMR)-deficient endome-
approaches. trial carcinomas, including none from our country.
The aim of this study was to analyse the role of T regulatory cells (Tregs), Methods: Based on requisitions and certain clinicopathologic features, 44
CD4 and CD8 T lymphocytes in low and high grade squamous cases of endometrial carcinomas were tested for MMR proteins, by immu-
intraepithelial lesions (LSIL and HSIL). nohistochemistry, out of which 23 cases were found to be MMR-deficient.
Methods: 62 patients were enrolled in the study in Riga East University Results: Age-range was 14-65 years(median=55); average tumour size
Hospital. Each patient had undergone a biopsy or electroexcision of the was 5.3cm and lower uterine segment (LUS) involvement in 9/15 cases
cervix. Immunostaining for CD4, CD8 and FOXP3 was performed on (60%). Histopathologically, all cases were endometrioid adenocarci-
tissue samples of normal (n=10) and LSIL (n=32) and HSIL (20) lesions. nomas, with FIGO grade 2 (n=6) and 3 (n=17), displaying de-differenti-
Results: Obtained results showed that patients the numbers of CD4 T- ated, undifferentiated and lymphoepithelioma (LE)-like patterns, in cer-
lymphocytes did not differed between the patients with LSIL and HSIL. tain cases. Tumour infiltration ≥ half of myometrium was seen in 14/19
However, patients with HSIL had significant CD8 T-lymphocytes upregula- cases (73.6%); lymphovascular emboli in 9/18 cases (50%); and nodal
tion compared to patients with LSIL (16± 4 vs. 8 ± 2 cells/mm2, p = 0.001). In metastasis in 4/9 cases. Immunohistochemically, tumour cells showed
addition patients with HSIL with concomitant epithelial koilocytosis demon- loss of MLH1 and PMS2 (n=19) and MSH2 and MSH6 (n=4); ER pos-
strated increased numbers of FOXP3 positive T-lymphocytes compared to itivity (7/23) (30.4%) and wild-type p53 staining (10/12) (83.3%).
patients with LSIL ( 12± 6 vs. 6 ± 2 cells/mm2, p = 0.02). Conclusion: Certain clinicopathologic features are suggestive for MMR-
Conclusion: Upregulation of T regulatory lymphocytes in patients with deficient endometrial carcinomas, including large-sized tumours, involving
HSIL suggested the pivotal role of Tregs for counteracting the host im- LUS in ≤ 55-year-old patients, harboring high-grade, infiltrative EMACs,
mune response for the progression from LSIL to HSIL. Prime targets for including de-differentiated, undifferentiated and LE-like patterns; showing
new immune-based non-invasive therapies for the HSIL treatment could less relatively frequent ER expression and wild-type p53 immunostaining.
be beneficial. This constitutes the first report on these tumours from our country.

PS-02-025 PS-02-027
Prognostic value of histopathological response in BRCA1-associated Shotgun lipidomics for differential diagnosis of HPV-associated cer-
and sporadic high-grade serous ovarian carcinomas vix transformation
G. Raskin1, A. Ivantsov2, T. Gorodnova2, E. Imyanitov2, A. Sokolenko2 V. Sergeeva1, N. Starodubtseva2, V. Chagovets2, M. Nekrasova2, A.
1
Academic A.M. Granov Scientific Center for Radiology and Surgical Tokareva3,4, A. Kononikhin3,1, N. Nazarova2, V. Frankevich2
Technology, Russia, 2 N.N. Petrov Institute of Oncology, Russia 1
Emanuel Institute for Biochemical Physics, Russian Academy of
Sciences, Russia, 2 V.I. Kulakov National Medical Research Center of
Background & Objectives: BRCA1-associated high-grade serous ovar- Obstetrics, Gynaecology and Perinatology, Russia, 3 V.L. Talrose Institute
ian carcinomas (HGSOC) are characterised by a pronounced response to for Energy Problems of Chemical Physics, Russian Academy of
platinum-based treatment. We compared the prognostic value of Sciences, Russia, 4 Moscow Institute of Physics and Technology, Russia
Virchows Arch

Background & Objectives: Cervical cancer keeps one of the leading that higher tumour grade and presence of lymphatic invasion were indepen-
positions in female mortality causes. It is preceded by cervical dently correlated with MMR protein deficiency.
intraepithelial neoplasia (low grade squamous intraepithelial lesion, Conclusion: In our study, overall 33% of cases exhibited loss of MMR
LSIL and high-grade squamous intraepithelial lesion, HSIL). Lipids are proteins and most were MLH1&PMS2 (86%) losses. Matthew et al.
potential indicators of pathological processes in a tissue, which is con- (USA) showed that loss of MSH6 protein expression was the commonest
firmed for such hyperproliferative disorders as breast cancer, glyoma, MMR defect in EC, whereas in our study we showed that the incidence of
lung cancer, endometriosis, etc. The objective of this study was to differ- loss of MSH6 protein expression was 9%.
entiate stages of HPV-associated cervix epithelium transformation using
shotgun lipidomics analysis of tissue Folch extracts.
Methods: Tissue samples from 74 HPV-positive women with cervicitis PS-02-029
(n = 20), LSIL (n = 20), HSIL (n = 20) and cervical cancer (n = 15) were Clinicopathologic association and prognostic value of MELF pattern
obtained along with a biopsy for histology. Cervical epithelial tissue in invasive endocervical adenocarcinoma (ECAs)
lipidome was studied by shotgun label-free semi-quantitative approach S. Stolnicu1, L. Hoang2, S. Segura3, M. Boros4, A. Pesci5, S. Aviel-
based on ESI-MS/MS method with subsequent orthogonal projections to Ronen6, T. Kiyokawa7, I. Alvarado-Cabrero8, K. Park9, E. Oliva10,
latent structures discriminant analysis (OPLS-DA) to build a classifica- R.A. Soslow11
1
tion model. Shotgun lipidomics allows obtaining molecular profile of a Department of Pathology, UMFST, Targu Mures, Romania,
2
sample within few minutes. Department of Pathology, Vancouver General Hospital, Canada,
3
Results: OPLS-DA of lipidomic data resulted in a statistical model dif- Memorial Sloan Kettering Cancer Center, New York, USA,
4
ferentiating benign, precancerous and malignant processes in the cervix. Department of Pathology, University of Medicine and Pharmacy,
A potential diagnostic features for the early differentiation of HSIL and Oradea, Romania, 5 Pathology-IRCCS Ospedale Sacro Cuore-Don
cervical cancer, represented by phosphatidylcholines (PC 32:0, PC 34:1, Calabria, Italy, 6 Department of Pathology, Sheba Medical Center, Tel-
PC 36:2), phosphatidylethanolamines (PE 38:4, PE 40:5) and Hashomer, Israel, 7 Department of Pathology, the Jikei University School
plasmalogens (РС О-16:3, РС О-38:5), were determined. Previously, of Medicine, Japan, 8 Department of Pathology, Hospital de Oncología
these lipids were associated with suppression of apoptosis, stimulation Mexico City, Mexico, 9 Department of Pathology, Memorial Sloane
of proliferation and impaired cell metabolism. Kettering Cancer Center, New York City, USA, 10 Department of
Conclusion: A diagnostic and potentially prognostic method for rapid Pathology, Massachusetts General Hospital, USA, 11 Department of
classification of HPV-associated cervix transformation stage was pro- Pathology, Memorial Sloan Kettering Cancer Center, USA
posed. This method can be used for early, rapid differential diagnostics
of the neoplastic process severity as a supplement to the histological Background & Objectives: As Anti-Her-2 containing therapy has be-
examination (analysis time is about 25 minutes). come an important treatment for Her-2 positive breast cancer. The ratio of
human epidermal growth factor receptor 2 (HER2) to CEP17 by fluorescent
The work was supported by RSF (#18-75-10097). in situ hybridization (FISH) with the centromeric probe CEP17 is evaluated
to determine HER2 gene status as a standardised method. But during the
interpretation of FISH, the result may be critical in tumours with chromo-
PS-02-028 some 17 polysomy defined as increased copy number of chromosome
Assessment of the relation between mismatch repair protein status enumeration prob (CEP˃2,5). The purpose of our study was to highlight
and histopathologic parameters in resection specimens of endometri- the clinocopathologics significant of chromosome 17 polysomy.
al cancers Methods: This is a retrospective analysis of a large series of 203 cases of
T. Soylemez1, G. Kir1, R.B. Girgin1, S.R. Dur2, I. Tosun3, H. Ankarali4, primary invasive breast carcinomas with equivocal HER2 IHC staining
A. Karateke5 (IHC HER2 2+) whom her-2 fluorescence in situ results and clinicopath-
1
Istanbul Medeniyet University, Department of Pathology, Turkey, ological data were available from 2012 to 2018 at the Department of
2
Istanbul Medeniyet University, School of Medicine, Turkey, Pathology of Hassan II University Hospital of Fes, in which we identify
3
Umraniye Training and Research Hospital, Department of Pathology, 15 cases of chromosome 17 polysomy.
Turkey, 4 Istanbul Medeniyet University, Department of Statistics, Results: As results, among 203 cases of invasive breast carcinoma
Turkey, 5 Istanbul Medeniyet University, Department of Obstetrics & analysed by FISH, 20% of the cases showed HER-2 gene amplification.
Gynaecology, Turkey A total of 15 (7,5%) cases showed the presence of polysomy 17. Absence
of polysomy 17 was seen in the remaining 188 cases. The two groups
Background & Objectives: The aim of the study was to analyse the polysomy and non-polysomy 17 were classified according to the HER2
correlation between DNA mismatch repair proteins (MMR) status and gene amplification status. Among 15 cases, 11 (73,3%) were HER-2 non-
clinicopathological characteristics of endometrial cancers (EC). amplified, 4 (25,7%) were HER-2 amplified. Among 188 non polysomy
Methods: A retrospective study was carried out in 131patients, who cases, 152 (80%) were HER-2 non amplified, 36 (20%) were HER-2
underwent total abdominal hysterectomy, bilateral salpingo- amplified. Polysomy 17 showed a significant association with poor path-
oophorectomy with/without regional lymphadenectomy from 2016 to ological parameters including low age (under 50ans p=0,06), low mitotic
2018. For each case we evaluated:tumour histology, tumour grade, score (p=0,05), high nuclear ploemorphism score (p=0,03) high histolog-
tumour-infiltrating lymphocytes, lymphatic invasion, vascular invasion, ical grade (p=0,03), presence of node metastasis (p=0,04), not otherwise
perineural invasion, cervical involvement, MELF pattern of invasion, specified histological type (p=0,009). Showed more often in positive
myometrium invasion, tumour size, lymph node metastases and tumour hormone receptors status and high KI-67 proliferation index. Similarly,
necrosis. Immunohistochemical evaluation of the MMR proteins (MLH1, in HER-2 non amplified gene, polysomy 17 showed an association with
PMS2, MSH2, MSH6) were performed. almost the same aggressive histological variable.
Results: 44 out of 131 (33%) cases showed immunohistochemical alteration Conclusion: In our study, we identified 7,35% cases of polysomy 17. We
of MMR proteins: 38 (29%) cases lost MLH1&PMS2, 1 (0,7%) case lost revealed that the polysomy 17 can serve as a poor prognostic marker in
MLH1, 3 (2%) cases lost MSH2&MSH6, 1(0,7%) case lost MSH6, 1 (0,7%) invasive breast cancer. We also highlight the prognostic value of
case lost PMS2. On univariate analysis, we observed significant association polysomy 17 in luminalB/HER-2 negative.
between MMR protein deficiency status and higher tumour grade (p=0.039).
Also, there was a marginal significance between MMR status and presence of This study was funded in part through the NIH/NCI Support Grant P30
lymphatic invasion (p=0.060). Binary logistic regression analysis revealed CA008748 (Dr. Soslow and Dr. Park).
 Virchows Arch

PS-02-030 staging procedures is a matter of debate. We investigated the effect of

Microsatellite instabillity, a prognostic factor for early stage endome- adjuvant chemotherapy on recurrence-free survival (RFS) and overall
trial cancers survival (OS) in a population-based cohort study.
G.E. Tasar Kapakli1, S. Lacin2, A. Usubutun3, Z. Arik4, Y. Karakas2, D. Methods: Patients diagnosed in the Netherlands between 2002-2014
Yuce5, M.C. Salman6, A. Kars2 with FIGO stage I HGSOC who underwent surgical staging were includ-
1
Department of Medical Pathology, Hacettepe University Faculty of ed. Data on clinical characteristics, histopathology and survival were
Medicine, Turkey, 2 Department of Medical Oncology, Hacettepe collected from the Netherlands Cancer Registry and Dutch Pathology
University Cancer Institute, Turkey, 3 Department of Medical Registry.
Pathology, Hacettepe University Faculty of Medicine, Turkey, We identified 393 patients of whom 223 patients underwent optimal
4
Hacettepe University Institute of Oncology, Department of Medical staging procedures. Of 223 optimally staged patients, 101 (45%) patients
Oncology, Turkey, 5 Hacettepe University Cancer Institute, Department received adjuvant chemotherapy. Following staging and chemotherapy,
of Preventive Oncology, Turkey, 6 Department of Obstetrics and 21% (21/101) of patients had recurrent disease, compared with 38% (46/
Gynaecology, Hacettepe University Faculty of Medicine, Turkey 122) of patients after staging without chemotherapy.
Results: Five-year RFS was 81% after staging plus chemotherapy and
Background & Objectives: Endometrial cancer (EC) is a heterogeneous 59% after staging only. Median time to recurrence was 32.2 and 26.8
disease with diverse histological features and biological behaviour. months, respectively. In the group of patients who underwent staging
Microsatellite instability (MSI) which occurs in cancerous tissue second- and chemotherapy, 21% had died, compared with 31% in the group of
ary to mismatch repair (MMR) defect of hereditary or somatic origin is a patients after staging alone. Five-year and ten-year OS were 84% and
well-known feature further diversifying genetic tumour landscape. In this 78% after staging and adjuvant chemotherapy, whereas five-year and
study, we aim to investigate the relationship between MSI and prognosis ten-year OS were 83% and 62% after optimal staging only (p=0.07).
in patients with early stage EC. Conclusion: After correction for age and FIGO stage, multivariable anal-
Methods: The patients diagnosed with EC between 2004 and 2017 in yses demonstrated a significant OS benefit from adjuvant chemotherapy
Hacettepe University were retrospectively analysed in the study. The surgery (p=0.02). Adjuvant chemotherapy improves RFS and long-term
demographic characteristics, disease stage, menopausal status, and clini- OS in patients with FIGO stage I HGSOC after optimal staging.
cal and laboratory values were noted. Immunohistochemically MLH1,
MSH2, MSH6 and PMS2 antibodies were used to detect microsatellite (Paper accepted for publication in Gynaecological Oncology, March 26,
status within the tumour tissue samples. Peritumoural lymphocytes and 2019)
tumour infiltrating lymphocytes are detected.
Results: The mean age of the 93 patients and menopause was 60.6 ± 9.8 and
49.68 ± 4.5 years, respectively. The median follow-up period was 28 (1-110) PS-02-032
months. At the time of diagnosis, number of the patients with stage IA, IB, II, The importance of BRCA mutational analysis starting from
III, and IV were 5, 64, 8, 14, and 2, respectively. Forty-three patients were Formalin Fixed Paraffin Embedded (FFPE) tissue: the Catania
grade 1, 23 patients grade 2, and 27 patients were grade 3. In terms of experience
microsatellite status, 59 patients (63.4%) were microsatellite stable (MSS) S. Vatrano1, A. Pettinato1, G. Scandurra2, S. Lionti1, J.M. Curduman1,
and 34 patients (36.6%) were microsatellite instable (MSI). There was no M.G. Tranchina1, G. Scibilia3, P. Scollo3, F. Fraggetta1
significant association between MSI and tumour stage or grade (X2 = 1.97 p = 1
Pathology Unit Cannizzaro Hospital, Italy, 2 Oncology Unit Cannizzaro
0.74 and X2= 3.2, p = 0.19, respectively). There was a significant relationship Hospital, Italy, 3 Gynaecology Unit Cannizzaro Hospital, Italy
between peritumoural lymphocyte infiltration rate (pTIL) and MSI. PTIL
ratio was higher in tumoural tissues with MSI, whereas pTIL was low in Background & Objectives: To underline the importance of switch
MSS tumour tissues (X2= 28.6, p < 0.0001). Patients with MSI tended to BRCA tumour testing in Ovarian cancer patients to identify simulta-
have poorer survival than patients with MSS irrespective of disease stage; neously both germline and somatic pathogenic mutations with a single
mOS rates were 76 and 91 months, respectively (p = 0.086). However, test, using targeted next generation sequencing (T-NGS) from Formalin
patients with early stage disease and MSI had significantly poorer survial in Fixed Paraffin Embedded (FFPE) tissue for predictive purposes.
comparison to patients with similar disease stage and MSS: Overall survival Methods: A total of 43 tumour samples with ovarian cancer were col-
rates for patients with MSI and MSS were 75.8 and 94.7 months, respectively lected at the Cannizzaro Hospital (Catania, Italy). Upon clinical request,
(Log-rank p = 0.048). the BRCA1/2 genetic analysis was performed by means of T-NGS using
Conclusion: There is a limited number of studies assessing the associa- The GeneReaderTM NGS System (GeneRead®QIAact BRCA 1/2 Panel,
tion between MSI and clinical outcomes in EC. Our study hints at the Qiagen). For all cases we performed on parallel the analysis starting from
presence of potential relationship between MSI and pognosis in patients peripheral blood samples.
with MSI. Similar to previous studies performed with various types of Results: All FFPE samples were sequenced successfully obtaining
tumours we found that EC with MSI attract more immune cells to tumour confident data. In many cases we performed Laser Microdissection to
microenvironments. Interestingly, patients with MSI tended to have exclude areas which could invalidate mutational test. The genetic
poorer prognosis despite augmented immune-cell inftration. results obtained from tumour tissue were confirmed with that derived
from correspondent blood (concordance 100%). Sixteen samples
(30%) harboured deleterious mutations in the investigated genes, 12
PS-02-031 (23%) were germline and four (7%) somatic. All but one were genetic
The effect of adjuvant chemotherapy on survival in patients with variants previously identified and reported in the main mutational
FIGO stage I high-grade serous ovarian cancer databases. Of note we obtained a composed heterozygous genotype
J. van Baal1, K. Van de Vijver2, M. Algera1, M. van der AA3, G. Sonke1, in four cases, who harboured pathogenic mutations with therapeutic
W. van Driel1, G. Kenter1, F. Amant1, C. Lok1 implications. The turn-around time (10 days) was in according with
1
The Netherlands Cancer Institute, The Netherlands, 2 Ghent University clinicians’ request.
Hospital, Belgium, 3 Netherlands Comprehensive Cancer Organisation Conclusion: Our data underlines the importance of switching BRCA
(IKNL), The Netherlands mutation analysis to somatic test in order to identify both somatic and
germline deleterious mutations with clinical and therapeutical implica-
Background & Objectives: The benefit of adjuvant chemotherapy for tions. The present job is one of the few which speculates about BRCA
FIGO stage I, high-grade serous ovarian cancer (HGSOC) after optimal somatic study.
Virchows Arch

PS-02-033 nodes. Although functions of PDCs are already recognized as innate-

Adult granulosa cell tumour with high-grade transformation: report immunity mediated by Toll-like receptor7 (TLR7) and TLR9, no report
of a series with FOXL2 mutation analysis of the relevant literature describes a study. As described herein, we ex-
Y. Fashedemi1, M. Coutts2, O. Wise3, B. Bonhomme4, I. Soubeyran4, S. plain the role of TLR7 and TLR9 in the PDCs of NEL.
Croce4, W.G. McCluggage5 Methods: During 1989-2016, data cases of NEL were collected.
1
Department of Cellular Pathology, Basildon University Hospital, United Lymph node samples were fixed in 10%-formalin, in 2.5%-glutaral-
Kingdom, 2 Department of Pathology, Maidstone General Hospital, dehyde for electron microscopy (EM) and fixed in 95%-ethyl alcohol
United Kingdom, 3 Department of Pathology, St Thomas Hospital, for imprint cytology. For immu nohistochemical analysis (IHC),
London, United Kingdom, 4 Department of Biopathology, Institute formalin-fixed paraffin-embedded tissue sections, were using an au-
Bergoniè, Comprehensive Cancer Center, Bordeaux, France, tomated stainer. Statistical analyses of changes of cells (CD4+, CD8+,
5
Department of Pathology, Belfast Health and Social Care Trust, CD123+, Mx1+, TLR7+, TLR9+ and UNC93B1+ cells) were facilitat-
Northern Ireland, United Kingdom ed by image analysis software (Image J 1.48 v; NIH, USA).
Results: We examined 70 patients (M/F=24/46). The peak of onset
Background & Objectives: Adult granulosa cell tumour (AGCT) is a was in the 20s. Most patients complained of painful cervical lymph
low-grade malignant neoplasm with a significant propensity for late re- nodes. Peripheral white blood cell counts, 46.6% of patients showed
currence and metastasis. Almost all AGCTs are composed of cells with lower than 4,000/mm3. Histological features included immunoblasts,
bland nuclear features and even when these tumours recur or metastasise, PDCs, histiocytes, and macrophages, the latter with phagocytized
the nuclear features are almost always low-grade. We report 5 cases of nuclear debris derived mainly from apoptotic lymphocytes. The num-
AGCT in patients aged 37 to 88 years composed of areas of typical ber of CD8+, Mx1+, CD123+, TLR7+ and UNC93B1+ cells in affect-
AGCT with low-grade morphology admixed with areas of high-grade ed lesions increased over time, but the number s of TLR9+ cells did
morphology, marked nuclear atypia and high mitotic activity. not change.
Methods: The cases derived from the pathology archives of the Institutions Conclusion: NEL is a systemic non-autoimmune disorder with charac-
to which the authors are affiliated together with the consultation practice of teristic clinical features. The pathogenesis of the disease remain obscure,
one of the authors (WGM). All available slides (haematoxylin and eosin but it might be associated with the imbalance between TLR7 and TLR9 of
and immunohistochemical stained) were reviewed. PDCs. Presumably, overexpression of TLR7 induced adaptive immunity.
Immunohistochemistry for p53, MIB1, inhibin and p16 was carried out Results show that PDCs play an important role of in the immune response
on both the low-grade and high-grade components of the tumour in all 5 of a person when affected by the disease.
cases.
FOXL2 mutation analysis was undertaken in 4 cases.
PS-03-002
Results: FOXL2 mutation analysis of both the low-grade and high-grade
Cancer stem-cell markers assessment in oropharyngeal squamous
components confirmed the presence of missense point mutation,
cell carcinoma: practical or not?
confirming that the high-grade component represents transformation of
M. Biskup-Fruzynska1, A. Stanek-Widera1, T. Rutkowski2, M. Snietura2,
typical AGCT rather than the coexistence of another sex cord-stromal
A. Kopec2, B. Nikiel2, D. Lange1
tumour. In cases where immunohistochemistry was undertaken, there 1
Tumour Pathology Department, Maria Sklodowska-Curie Memorial
was wild-type staining of p53 in the low-grade and mutation-type expres-
Cancer Center and Institute of Oncology, Gliwice Branch, Poland,
sion in high-grade components; p16 was more diffusely expressed in 2
Maria Sklodowska-Curie Institute - Oncology Center Gliwice Branch,
high-grade component. Follow-up in 3 of the 4 stage IA neoplasms (6-9
Poland
months) revealed no tumour recurrence.
Conclusion: High-grade transformation is uncommon in AGCTs and
Background & Objectives: Cancer stem cells (CSC) have been investi-
given the limited follow-up in our cases, the clinical significance is un-
gated in various human neoplasms and in some proved as predictive
certain. However, given that 1 of our cases was advanced stage at diag-
factors. The aim of the study was to analyse the expression of CSC
nosis and that there have been occasional case reports of aggressive be-
markers in oropharyngeal squamous cell carcinomas (OPSCC) and its
haviour in AGCTs with high-grade transformation, this may herald an
correlation with histopathological and clinical data.
aggressive clinical course.
Methods: Tissue samples from 92 OPSCC cases diagnosed and treated in
our Institution from 2002 to 2018 with HPV status tested by PCR were
Sunday, 8 September 2019, 09:30 - 10:30, Agora 3 subjected to immunohistochemical assays for CD44, ALDH1A1, CD98,
Ki67 and PHH3. Markers’ expression was assessed by light microscopy
PS-03 | Head and Neck Pathology
and correlated with patients’ and tumours’ characteristics and clinical
outcomes.
Results: The study group comprised 64 male and 28 female patients
PS-03-001 (mean age 58,8), 53 HR-HPV(+) and 39 HR-HPV(-), 53,3% in at least
Necrotising lymphadenitis might be induced by over expression of AJCC stage III. Significantly higher expression of CD44 was found in
Toll-like receptor7(TLR7) caused by reduction of TLR9 transport in HR-HPV(-) tumours (p<0,0001). CD44 was also the only parameter that
plasmacytoid dendritic cells (PDCs). demonstrated significant differences in overall survival between „low”
S. Asano1, H. Sato2, H. Naito2, K. Yamazaki1, K. Mori1, H. Wakasa3, H. and „high expressors” (p=0,0473). Significantly higher PHH and Ki67
Suzuki4 counts were noted in the HR-HPV(+) group (p=0,0118 and 0,0049, re-
1
Pathology Center/Iwaki Medical Center, Japan, 2 Oral Surgery/Iwaki spectively). Lower PHH3 and Ki67 counts were identified in CD44(+)
Medical Center, Japan, 3 Pathology/Surgical Pathology Japan, Japan, 4 and CD98(+) tumours, respectively, which is consistent with CSC being
Paediatrics/Iwaki Medical Center, Japan mostly quiescent, slow-dividing cells. ALDH1A1 and CD98 expression
was not found statistically significant in correlation with the evaluated
Background & objectives features.
The pathogenesis of necrotizing lymphadenitis (NEL), characterised by Conclusion: The results suggest that CSC marker CD44 might be useful
blastic transformation of CD8+ cells and apoptosis of CD4+ cells, remains in the management of OPSCC patients. The obtained data need revision
obscure. With NEL, innumerable plasmacytoid dendritic cells (PDCs), after digital image analysis as human eye might be an imperfect tool for
produce large quantities of interferon-α (IFN-α), are observed in lymph membranous and cytoplasmic staining evaluation.
 Virchows Arch

PS-03-003 PS-03-005
Metastatic angiosarcoma in the jawbone: case report and review of Immunoexpression of prolactin receptor is not restricted to the secre-
metastatic tumours in oral cavity in "Hospital Universitario La Paz" tory carcinoma in salivary glands
in the last 15 years M. Custódio1, B. Tavares Sedassari2, F. Daumas Nunes1, A. Altemani3, S.
O. Cerezo-Aranda1, O.B. Popescu1, E. Ruiz-Bravo1 COM de Sousa1
1 1
Hospital Universitario La Paz, Spain University of São Paulo, Brazil, 2 Universidade Nove de Julho, Brazil,
3
University of Campinas, Brazil
Background & Objectives: We report a case of metastatic angiosarcoma in
the jawbone as first manifestation. Angiosarcoma is a high grade, malignant Background & Objectives: Prolactin receptor is crucial for the devel-
neoplasm of cells that demonstrate endothelial differentiation. It accounts for opment of lactating-competent mammary glands. Recently, it has
less than 1% of sarcomas and very few primary cases are reported in oral been proposed that secretory carcinoma of salivary gland origin
cavity. could have a lactating-like differentiation based on its morphology
Methods: We present a 53 years old male with a rapidly growing mass in and some immunohistochemical features. This salivary carcinoma is
vestibular gum. CT shows an insuflating mass in left jawbone extending a very rare neoplasm similar in many aspects to its breast counterpart.
to maxillary sinus. Biopsy of the maxillar mass is performed. On CT-PT Therefore, we aimed to assess the expression of the prolactin receptor
there is an intense captation focus corresponding to a 5cm mediastinal in secretory carcinoma of salivary gland origin. We hypothesized that
mass that invades pericardium and aorta. There were also other masses in the expression of this receptor would be restricted to this type of
cervical spine, sternal manubrium and clavicula. salivary tumour.
Results: We receive several fleshy fragments which microscopically corre- Methods: Prolactin receptor (D4A9) immunostaining was performed in
spond to a cellular proliferation with irregular, different sized vascular chan- seven cases of secretory carcinoma and twenty-seven other salivary car-
nels, lined by highly pleomorphic cells with a high amount of mitotic figures. cinomas (AdCC, adenoid cystic carcinoma=9; MEC, mucoepidermoid
Inmunohistochemically, cells express vimentin, CD31 and focal keratin AE1/ carcinoma=10, SDC, salivary duct carcinoma=4; ACC, acinic cell
AE3 and are negative for HHV8, SMA, desmin, CD99 and BCL2. Final carcinoma=4).
diagnose is metastatic angiosarcoma, with a probable cardiac origin. Results: A weak and focal staining was seen in the cytoplasm of 3/7 cases
Conclusion: Metastatic angiosarcoma is a very rare tumour. Besides, the of secretory carcinoma. Tumour secretion was weakly stained in one case.
fact of metastatizing in oral cavity makes this case extremely uncommon. Among the other salivary carcinomas, 11/27 were positive (AdCC=2;
We made a review in our hospital for metastatic tumours in oral cavity in MEC=6; SDC=1; ACC= 2). Almost all of them had a focal and weak
the last 15 years with a result of 10. All of them, except the present case staining in the cytoplasm. Interestingly, the expression of prolactin recep-
were carcinomas from different origins (mainly pulmonary and diges- tor was also observed in normal salivary glands. Strong staining was seen
tive). Nevertheless, when an angiosarcoma is found in oral cavity, we in a subset of acinar cells and weak staining in some intra e interlobular
have to take into account that it could be a metastatic one. ducts. Mucous cells rarely stained.
Conclusion: Among salivary carcinomas, the expression of prolactin
PS-03-004 receptor is not restricted to the secretory carcinoma. The staining was
Immunoexpression of mTOR downstream targets in seven cases of observed both in normal salivary glands and their derived tumours, which
secretory carcinoma of salivary gland origin suggests a different function for this receptor in salivary glands.
M. Custódio1, B. Tavares Sedassari2, S. COM de Sousa1, M.F. Setúbal
Destro Rodrigues2, A. Altemani3, F. Daumas Nunes1 This work was supported by Fundação de Amparo à Pesquisa do Estado
1
University of São Paulo, Brazil, 2 Universidade Nove de Julho, Brazil, de São Paulo [grant #17/04546-9].
3
University of Campinas, Brazil

Background & Objectives: The secretory carcinoma of salivary gland PS-03-006

origin is a very rare neoplasm recently described as the counterpart of the Comparison of three PD-L1 immunohistochemical assays in head
secretory breast carcinoma. Both neoplasms frequently have the ETV6- and neck squamous cell carcinoma
NTRK3 fusion gene as a result of a balanced chromosomal translocation. E. de Ruiter1, F. Mulder2, E. Speel3, M. van den Hout2, R. de Roest4, E.
This fusion gene can constitutively activate important signalling pathways in Bloemena5, L. Devriese6, S. Willems7
1
cancers, such as Akt/mTOR and MAPK. Therefore, we aimed to assess the Department of Pathology, University Medical Center Utrecht,
expression of the mTOR downstream targets S6 ribosomal protein, eIF4E The Netherlands, 2 Department of Pathology, Maastricht University
and 4E-BP1 in the secretory carcinoma from salivary glands. Medical Center, The Netherlands, 3 Maastricht University Medical
Methods: After searching in our pathology files, we retrieved seven cases Centre+, The Netherlands, 4 Department of Otolaryngology/Head and
of secretory carcinoma diagnosed by a combination of immunohistochem- Neck Surgery, Amsterdam University Medical Center, The Netherlands,
5
istry and/or molecular testing. Immunohistochemical assessment was made Department of Pathology, Amsterdam University Medical Center,
against phospho-S6 ribosomal protein, phospho-4E-BP1 and eIF4E. The Netherlands, 6 Department of Medical Oncology, University
Twenty-seven other salivary carcinomas were included for comparison. Medical Center Utrecht, The Netherlands, 7 Department of Pathology,
Results: eIF4e was diffusely positive in the cytoplasm of most cases, both University Medical Centre Utrecht, the Netherlands
for secretory carcinoma (5/7) and for other salivary carcinomas (25/27). 4E-
BP1 was less frequently expressed in both groups, being its expression Background & Objectives: Soon, expression of programmed death li-
especially seen in the cytoplasm and nucleus of 3/7 cases of secretory carci- gand 1 (PD-L1) will be implemented as predictive biomarker for immu-
noma and in only 8/27 of other salivary carcinomas. Regarding S6 ribosomal notherapy in head and neck squamous cell carcinoma (HNSCC). Several
protein, (2/7) 28.6% and (15/27) 55.5% of secretory carcinoma and other antibodies are available for PD-L1 testing and multiple staining and scor-
salivary cancers, respectively, were positive in a focal cytoplasmic pattern. ing methods are used. This study aimed to compare the performance of
Conclusion: mTOR downstream targets are present in secretory carcino- two PD-L1 standardised assays (SP263 and 22C3) and one laboratory-
ma in different expression patterns, although only eIF4E was highly developed test (LDT) (22C3) in HNSCC using the tumour proportion
expressed in the majority of cases. score (TPS) and the combined positive score (CPS).
Methods: Pre-treatment biopsies from 147 HNSCC patients were col-
This work was supported by "Fundação de Amparo à Pesquisa do Estado lected in a tissue-microarray (TMA). Serial sections of the TMA were
de São Paulo"[grant #17/04546-9]. immunohistochemically stained for PD-L1 expression using SP263 on
Virchows Arch

the Ventana Benchmark Ultra platform, 22C3 on the Dako Link 48 plat- specimens. The precise etiology, whether treatment-related or not, is not
form, and 22C3 as an LDT on the Ventana Benchmark Ultra. Stained well established.
slides were assessed for TPS and CPS. Cutoffs of ≥1% and ≥50% for The aims of this study were to report the clinico-pathological features of 6
TPS, and ≥1% and ≥20% for CPS were used. cases.
Results: Concordance between the different staining assays was moder- Results: The gender ratio was 4:2 (female:male), the age ranged 33-
ate for TPS (intraclass correlation coefficient (ICC) 0.70) as well as for 73 years. The clinical diagnoses were amylosis (1) and dry syndrome
CPS (ICC 0.53). When stratifying patients by clinically relevant cutoffs, (5). The medical history suggested hypophysis adenoma in 2 cases.
considerable differences between the assays were observed: for TPS, The histology diagnosis was that of chronic sialadenitis: grades 1, 2
concordance was moderate (kappa 0.56), while for CPS, concordance and 4 (1,2 and 3 cases respectively). Granulomas were detected in 1
was poor (kappa 0.44). Generally, SP263 stained a higher percentage of case, oncocytic metaplasia in 4. A history of corticoid treatment was
cells than the other assays, especially when using the CPS. known for 1 case. Polykariocytes (1-6/biopsy) were detected in the
Conclusion: Moderate concordance was observed between three different basal lining of the duct epithelium (interlobar and excretory ducts, 4
PD-L1 immunohistochemical assays and considerable differences in PD-L1 and 2, respectively), on 1 or 2 tissue sections (2 and 4 biospsies,
positivity were observed when using clinically relevant cutoffs. This should respectively). When observed on 2 sections, they belonged to the
be taken into account when using PD-L1 expression to guide clinical practice. same level of section. Therefore P63 staining may be of limited help
for the differential diagnosis with fibroblasts. There was no inflam-
E. J. de Ruiter is financially supported by the Dutch Cancer Society mation at contact to the polycaryocytes or inflammatory exocytosis.
(project number: A6C 7072). Oncocytic metaplasia was detected in all samples, for one of them in
the same duct as the polycaryocytes.
Conclusion: In conclusion, minor salivary gland duct polykaryocytes
PS-03-007 may be detected in the context of chronic sialadenitis (associated or not
Comparison of multiple methods detection of high-risk human pap- to granuloma), in excretory or interlobular ducts, however not as part of
illomavirus infection in 148 Polish patients with oropharyngeal the inflammatory lesions (inflammatory exocytosis). Further studies are
carcinoma required for precising their etiology.
M. Durzynska1, A. Szumera-Cieckiewicz2, M. Prochorec-Sobieszek3
1
Maria Sklodowska-Curie Institute - Oncology Center, Department of
Pathology and Laboratory Medicine, Poland, 2 Institute of Haematology PS-03-010
and Transfusion Medicine, Diagnostic Haematology Department, Histological features and outcomes of polymorphous adenocarcino-
Poland, 3 Department of Pathology, The Maria Skłodowska-Curie ma of minor salivary glands: a retrospective study of 38 cases
Memorial Cancer Center and Institute of Oncology, Warsaw, Poland S. Lerias1,2, I. Fonseca1,2
1
Instituteo Portugues de Oncologia de Lisboa, Francisco Gentil,
Background & Objectives: Human papillomavirus (HPV) is now rec- Portugal, 2 Instituteo de Anatomia Patologica, Faculdade de Medicina
ognized as an etiologic factor in oropharyngeal carcinoma. Evaluation of da Universidade de Lisboa, Portugal
HPV has a prognostic significance, but there is no agreement about the
most appropriate method of virus detection so far. Background & Objectives: Although most polymorphous adenocarci-
The aim of this study was to determine the optimal assessment of HPV nomas (PAC) have an indolent course, some cases show varying recur-
infection in oropharyngeal carcinoma using different methods. We also rence rates. In this study, we aimed at identifying the pathological features
investigated the correlation between clinical and histological patients pro- that can determine recurrence rates in 38 PAC.
file and HPV status. Methods: We reviewed 38 cases of PAC with clinical, histological and
Methods: Paraffin blocks were collected from 148 patients with primary prognostic data diagnosed over a period of 16 years (2002-2018).
oropharyngeal cancer diagnosed between 2007 and 2017 in Oncology Statistical analysis was performed using T-test and Chi-squared test.
Cancer Centre-Institute in Warsaw. The immunohistochemical (IHC) expres- Results: 26 (68%) of the patients were females, with a mean age at
sion of p16 was detected with CINtec p16 Histology. DNA HPV was tested diagnosis of 61.3yrs. The median follow-up period was 6.7yrs. The most
by in situ hybridization (ISH) using Inform HPV III Family 16 probe and by common site was the palate. Average tumour size was 2.5cm. Recurrence
polymerase chain reaction (PCR) using automatic system Cobas 4800. occurred in 7 cases, including 3 local recurrences, 1 nodal recurrence, and
Results: There were different results of HPV positive cases according to 3 distant metastasis, up to 9yrs after the initial resection. 37% of the
using method IHC, ISH and PCR: 56%, 48% and 58% of cases. The patients were pT1, 34% pT2 and 26% pT4. 9 patients were initially
combination of IHC and ISH classified 46% of the samples as HPV- treated with surgery, 29 with surgery and radiotherapy. The 5-years over-
positive, whereas the combination of IHC and PCR and the combination all survival rate was 100%, and 5 patients died of disease (range 8 to
of IHC, ISH, and PCR classified 53% cases as HPV-positive. There were 16.7yrs). Histologic evaluation showed that solid architecture was pre-
correlations between HPV status and patients sex, history of smoking, dominant (41%), followed by cribriform (30%). Recurrent cases were
tumour site, tumour staging, nodal involvement and morphology subtype more likely to have bone invasion (p=0.04), lymphovascular invasion
of squamous cell carcinoma. (p=0.03), lymph node metastasis (p=0.02), atypical mitosis (p=0.02),
Conclusion: The current study suggests that using a combination of IHC, optically clear nuclei (p=0.04) and ≥30% papillary architecture (p=0.01).
ISH, and PCR in a three-tiered, staged algorithm leads to the appropriate Conclusion: Bone invasion, lymphovascular invasion and lymph node
assessment of HPV. The prevalence of HPV infection in 148 Polish pa- metastasis are significant parameters that can predict adverse clinical
tients is approximate to results from western countries. behaviour in PAC. Atypical mitosis, optically clear nuclei and the per-
centage of papillary pattern are associated with high rates of recurrence
and should be documented as relevant prognostically parameters.
PS-03-008
Salivary gland duct polycaryocytes: features of 6 cases
A. Handra-Luca1 PS-03-011
1
APHP University Paris Nord, France Diagnostic and prognostic significance of HuR protein expression in
salivary gland tumours
Background & Objectives: Salivary gland duct polycaryocytes may be G. Levidou1, P. Sarantis2, G. Tsourouflis3, N. Tsoukalas2, E. Dana2, M.
observed on labial minor salivary gland biopsies, similarly to breast Karamouzis4, J. Klijanienko5, S. Theocharis2,6
 Virchows Arch

1
Humanpathologie Dr. Weiß GmbH, Germany, 2 First Department of Synaptophysin (80%vs100%) and more Chromogranin (80%vs60%) ex-
Pathology, Medical School, National and Kapodistrian University of pression in NEC (vs ON). CD56 was expressed in all but 1 (ADC) case,
Athens, Greece, 3 2nd Department of Propedeutic Surgery, School of being the only positive NE-marker in SNUC. EN treatment always in-
Medicine, National and Kapodistrian University of Athens, Greece, cluded Chemotherapy+/-Radiotherapy, while 40%ON were exclusively
4
Department of Biological Chemistry, Medical School, National and surgically managed.
Kapodistrian University of Athens, Greece, 5 Department of Pathology, Conclusion: NE-markers are variably expressed in SN-SRBCT of differ-
Institute Curie, Paris, France, 6 Department of Pathology, Institute Curie, ent origins, highlighting that this feature is not pathognomonic of NEC.
Paris, France Our series is thus consistent with previously published data.
Differentiating NECs from ON is of particular importance, and integra-
Background & Objectives: HuR protein is a post-transcriptional regu- tion of clinical, radiological and histological features is essential for the
lator of several genes expression, being correlated with carcinogenesis or/ accurate diagnosis and further optimal management of these patients.
and cancer patients’ prognosis. Research data on the role of HuR protein
in salivary gland tumours (SGTs) remain limited, whereas there is a pau-
city of information regarding its prognostic significance. In this study we PS-03-013
aim to investigate the potential diagnostic and prognostic significance of Salivary gland biopsy for Sjögren syndrome: is it worth it?
HuR protein expression in SGTs. R. Machado-Neves1, A. Lopes2, J. dos Santos2, R. Pereira2, M. Honavar1
1
Methods: HuR expression (positivity, intensity of staining and their Pathology Department - Hospital Pedro Hispano, Portugal, 2 Internal
combination as H-score) was assessed immunohistochemically in 50 Medicine Department - Hospital Pedro Hispano, Portugal
SGT tissue specimens (29 benign and 21 malignant) and was statistically
correlated with the clinicopathological characteristics for all cases and Background & Objectives: Labial accessory salivary gland biopsy is a
patients’ survival rate in malignant SGTs. minimally invasive procedure, frequently used for the diagnosis of
Results: Nuclear HuR immunostaining was observed in all (100%) and Sjögren’s syndrome (SS). Focal lymphocytic sialadenitis is one of the six
cytoplasmic in 42.5% of SGTs cases. Increased cytoplasmic and nuclear criteria of the American-European Consensus Group Classification for the
HuR immunostaining was more frequently found in malignant compared diagnosis of SS. The Chisholm-Mason scale is used to evaluate focal lym-
to benign SGTs (p=0.031 and p=0.006, respectively). Significant differ- phocytic infiltration in the salivary gland. Infiltrates of ≥1 focus of lympho-
ence was also found in cytoplasmic and nuclear HuR H-score between cytes per 4 mm2 are considered positive, corresponding to Chisholm-Mason
low grade and high gradeSGTs (p=0.003 and p=0.008 respectively). scores 3 and 4. We correlated the biopsy findings with the clinical
Finally, in survival analysis cytoplasmic HuR H-score was correlated manifestations.
with unfavourable patients’ prognosis (p=0.022). Methods: A retrospective analysis of the clinical files and histological
Conclusion: HuR protein seems to have a diagnostic role discriminating slides of salivary gland biopsies performed from April 2014 to December
malignant and benign SGTs and additionally, is correlated with a more 2017 at Hospital Pedro Hispano, Matosinhos, Portugal.
aggressive phenotype, emerging as a significant adverse prognosticator Results: 179 biopsies were performed, 129 (72%) with a clinical suspi-
for patients with malignant SGT. cion of SS and the rest for diverse clinical diagnosis (mainly amyloidosis
and sarcoidosis). Of the 129 patients with clinical suspicion for SS, the
mean age was 57 years (23-89) and 111 (86%) were female. 52 (40%) had
PS-03-012 score ≥3 on the Chisholm-Mason scale. Before the salivary gland biopsy,
Sinonasal small round blue cell tumours with expression of neuroen- only 9 (7%) patients met diagnostic criteria of SS. This number rose to 25
docrine markers - a clinicopathological characterisation of 14 cases (19%) based on the result of the biopsy.
and literature review Conclusion: Labial salivary gland biopsy is a simple procedure which is
S. Lopes Petronilho1, J. Costa1, R. Henrique1, M. Jácome1 critical for some clinical purposes. In our group of patients, a positive
1
Pathology Department, IPO-Porto, Portugal result on salivary gland biopsies more than duplicated the number of
patients diagnosed as SS.
Background & Objectives: Reaching the final diagnosis of small round
blue cell tumours (SRBCT) is universally challenging, but the inherent
complexity of the sinonasal (SN) region entails additional difficulties. PS-03-014
Differential diagnoses include epithelial, neuroectodermal, mesenchymal Tumour budding seems to be independent to epithelial-mesenchymal
and hematolymphoid neoplasms, which morphologically and transition in intestinal-type sinonasal adenocarcinoma
immunohistochemically overlap. In particular, neuroendocrine (NE)-mark- V. Maffeis1, R. Cappellesso2, F. Galuppini3,4, M. Boscolo5, L. Ventura5,
er expression has been described in several “non-neuroendocrine” tumours, A. Fassina2
1
perpetuating the debate on how to properly define a NE-neoplasm. Surgical Pathology & Cytopathology Unit, Department of Medicine-
Aim: To review clinicopathological features of SN-SRBCT with NE- DIMED, University of Padua, Italy, 2 University of Padua, Italy,
3
differentiation. Women's & Children's Health Department (SDB), University of
Methods: We retrospectively identified 14patients diagnosed with non- Padua, Italy, 4 Pathology Unit, Department of Medicine (DIMED),
hematolymphoid SN-SRBCT with expression of NE-markers University of Padua, Italy, 5 Department of Statistics, University of
(synaptophysin/chromogranin/CD56), in IPO-Porto (2013-2018). These Padua, Italy
included 6 Olfactory Neuroblastomas (ON) and 8 Epithelial Neoplasms
(EN), namely 6 small-cell Neuroendocrine Carcinomas (NEC); 1 Background & Objectives: Intestinal-type sinonasal adenocarcinoma
Undifferentiated Carcinoma (SNUC) and 1 Adenocarcinoma (ADC). (ITAC) is a rare malignant tumour morphologically, immunophenotypically,
Clinical(age/sex/treatment/follow-up), radiological (site/size) and patho- and molecularly resembling colorectal adenocarcinoma (CRC). Tumour bud-
logical (diagnosis/morphology/immunohistochemistry) data were col- ding is a well-established adverse prognostic marker in CRC and other tu-
lected from the patients’ files. mours, such as oral squamous cell carcinoma, with features of epithelial-
Results: EN occurred exclusively in males. ON occurred equally in both mesenchymal transition (EMT). The aim of this study was to assess tumour
sexes, and in older patients (median:57vs51). Overall, median size was budding in ITAC and to evaluate its possible association with EMT markers in
4,9cm (range:3,2-7,6). Most tumours (93%) primarily involved the nasal this setting.
cavity and infiltrated adjacent structures. Cytokeratins were diffusely Methods: 32 FFPE surgically resected specimens of CK20 and CDX2
positive in all EN, but focal (40%)/negative (60%) in ON. There was less positive ITAC have been evaluated for tumour budding according to the
Virchows Arch

international recommendations developed for CRC. The expression of targeted therapy when a certain genetic alteration is present. Previously, we
the EMT markers E-cadherin, ZEB2, SLUG, and SNAIL was evaluated demonstrated that in the Netherlands molecular testing was suboptimal in
by immunohistochemistry (IHC). Results were stratified using clinical 2015, as 25% (EGFR/KRAS and ALK) to 50% (ROS1) of patients were
and follow-up data (2/32 patients had metastatic disease and 4/32 died not tested according to guidelines, and notable laboratory variation was pres-
of disease). ent. Currently, by analyzing a cohort of metastatic NSCLC from 2017 we aim
Results: Tumour budding was observed in 13/32 (40.6%) ITAC cases to assess whether the performance of molecular testing improved.
including all the 9 patients with relapse (p = 0.07). Absence of tumour Methods: All fully registered stage IV non-squamous NSCLC with in-
budding was observed only in patients without relapse and it was associ- cidence year 2017 from the Netherlands Cancer Registry were matched to
ated with low ZEB2 expression (p = 0.03). No others association with E- the Dutch pathology registry (PALGA). Using information extracted
cadherin, SLUG, and SNAIL emerged. Occupational exposure to wood from pathology excerpts, proportions of tumours tested for
and leather dust was not related to the presence of tumour budding. EGFR/KRAS, BRAF, and HER2 mutation, ALK, ROS1, and RET rear-
Conclusion: Tumour budding is associated with a worse prognosis in ITAC. rangement <3 months after diagnosis were determined.
However, current findings do not seem to support an involvement of EMT in Results: Of 2596 identified patients, we have currently analysed 511
this specific setting. Further larger studies are needed to address this point. (20%). Twenty-three patients were non-eligible after matching, leaving
488 patients. EGFR/KRAS testing was performed in 412 patients
(84.4%). Of the EGFR/KRAS wildtype tumours (n=184), 167 (90.8%)
PS-03-015 were tested for BRAF, 158 (85.9%) for HER2, 157 (85.3%) for ALK, 110
Odontogenic cysts of inflammatory origin: reclassification according (59.8%) for ROS1, and 73 (39.7%) for RET. Insufficient tumour tissue
to the 2017 World Health Organisation Classification and inappropriate specimen were the most stated reasons for not testing.
I. Msakni1, F. Gargouri1, R. Hedhli2, N. Mansouri1, A. Saidi1, A. Conclusion: These preliminary data show significantly higher
Bouziani1, B. Laabidi3,4 EGFR/KRAS and ALK testing proportions compared to 2015. Further
1
Pathology Department; Military Hospital for Instruction of Tunis, improvement remains possible to identify candidates for targeted therapy.
Tunisia, 2 Tunis El Manar University, Medicine School of Tunis At the ECP meeting, we expect to present the variation between labora-
Military Hospital of Tunis, Department of Pathology, Tunisia, 3 Tunis tories for the entire cohort.
El Manar University, Medicine School of Tunis, Tunisia, 4 Military
Hospital of Tunis, Department of Pathology, Tunisia
PS-03-017
Background & Objectives: The 2017 World Health Organisation Comparative analysis of claudin expression in odontogenic tumours
(WHO) head and neck classification brought several changes. One was E. Phattarataratip1, K. Sappayatosok2
1
the reinstatment of a specific classification of the odontogenic cysts. Chulalongkorn University, Thailand, 2 Rangsit University, Thailand
There were two types odontogenic cysts of inflammatory origin.
Radicular cyst associated with non-vital teeth and Inflammatory collateral Background & Objectives: Claudins are integral to the structure and
cyst arising on the roots of partially or recently erupted teeth as a result of function of tight junctions. Altered claudin expression has been shown
inflammation of the pericoronal tissues. to affect disease behaviour and patient prognosis in various neoplasms.
Our aim was to reclassify odontogenic cysts of inflammatory origin ac- The objectives of this study were to analyse the claudin-1, -4 and -7
cording to the 2017 WHO classification. expression in odontogenic tumours and characterise their expression pat-
Methods: It was a retrospective study of odontogenic cysts of inflammatory tern in distinct tumour cell types in relation to the recurrence potential.
origin collected at our department over a period of 5 years (2012-2017). The Methods: Sixty-nine cases of odontogenic tumours, including 43
slides were reviewed based on clinical and radiological information. ameloblastomas (AM), 17 adenomatoid odontogenic tumours (AOT), 6
Results: We collected 83 inflammatory odontogenic cysts. Radicular cyst ameloblastic fibromas (AF) and 3 ameloblastic carcinomas (AC) were inves-
was observed in 48 cases. The median age was 39 years (sex ratio=4,33). tigated for claudin-1, -4 and -7 expression immunohistochemically. The stain-
Inflammatory collateral cyst was observed in 18 cases. The median age was ing was analysed semi-quantitively and categorized into 4 levels, based on the
36 years (sex ratio=5). Seventeen were unclassifiable inflammatory cysts. percentage of positively stained neoplastic epithelial cells.
After revision of the slides, 49% of inflammatory collateral cysts (n = 21) Results: Claudin-1 was expressed in all AOT and AF, whereas most AC
were reclassified to radicular cysts, 14% of radicular cysts (n = 6) to (66.7%) showed no expression. Claudin-1 staining was moderate-to-
unclassifiable inflammatory cyst and one case of unclassifiable inflam- intense in odontogenic epithelium of AF, but weak in those of AM.
matory cyst to dentigerous cyst. Claudin-7 was noted in all tumours studied, while claudin-4 expression
Conclusion: In our study, histological diagnosis after revisions of the was limited and mainly localized in squamous cells of AM and AC. AM
slides based on clinical and radiological information did not agree with showed higher claudin-4, but lower claudin-7 expression than AOT. AC
the initial diagnosis in 34% of cases. This is due to the lack of clinical and showed reduced claudin-1 immunoreactivity, compared to AOT. Low
radiological data for the pathologist, but also to the absence of a specific claudin-1 in AM was significantly associated with increased recurrence.
classification to odontogenic cysts up to the year 2017. Conclusion: Odontogenic tumours are differentially expressed claudin pro-
teins. The loss of claudin-1 may underlie the locally invasive nature of AM.

PS-03-016 This study was funded by a Research Fund, Faculty of Dental Medicine,
Primary intraosseous carcinoma of jaw: a clinicopathological study Rangsit University.
of 4 cases
M.I. Oviedo Ramírez1, A. Caballero Illanes1, A. Salazar Nicolás1, L.
Barona García 1, M.I. Ortuño Moreno 1, V. Caballero Illanes2, V. PS-03-018
Villanueva San Vicente2, E. Martínez Barba1 Clinical significance of Histone Deacetylase (HDAC)-1, -2, -4 and -6
1
Servicio de Anatomía Patológica. Hospital Clínico Universitario Virgen expression in salivary gland tumours
de la Arrixaca, Spain, 2 Hospital Clínico Universitario Virgen de la D. Pouloudi1, M. Manou1, P. Sarantis2, N. Tsoukalas2, G. Tsourouflis3, E.
Arrixaca, Spain Dana1, M. Karamouzis4, J. Klijanienko5, S. Theocharis1
1
First Department of Pathology, Medical School, National and Kapodistrian
Background & Objectives: Adequate and timely testing for genetic alter- University of Athens, Athens, Greece, 2 First Department of Pathology,
ations in non-small cell lung cancer (NSCLC) is necessary to consider Medical School, National and Kapodistrian University of Athens, Greece,
 Virchows Arch

3
2nd Department of Propedeutic Surgery, School of Medicine, National and L. Ruiter1, A. de Lange1, M. Wekking2, M. Philippens3, S. Willems1
Kapodistrian University of Athens, Greece, 4 Department of Biological 1
Department of Pathology, University Medical Center Utrecht,
Chemistry, Medical School, National and Kapodistrian University of The Netherlands, 2 Department of Pathology, Radboud University
Athens, Greece, 5 Department of Pathology, Institute Curie, Paris, France Medical Center Nijmegen, The Netherlands, 3 Department of
Radiotherapy University Medical Center Utrecht, The Netherlands
Background & Objectives: Histone Deacetylases (HDACs), through
post-translational histone modifications and subsequent gene expression Background & Objectives: The tumour microenvironment (TME) is
alterations, are thought to play a key role in carcinogenesis. Aim of this crucial for tumour growth and plays an important role in treatment fail-
study was to evaluate the clinical significance of different HDAC mem- ures and recurrences of cancer. Individual specialized cell types construct
bers’ expression in salivary gland tumours (SGTs) and their potential use the TME biology and the course of the tumourigenesis. The aim of this
as diagnostic or prognostic biomarkers. study is to find correlations between TME characteristics, such as vascu-
Methods: HDAC-1, -2, -4 and -6 expression (positivity, intensity of larization, immune cell influx and tumour features like hypoxia, keratini-
staining and their combination as H-score) was assessed zation and tumour cell proliferation in laryngeal squamous cell carcinoma
immunohistochemically in 58 SGT tissue specimens (36 benign and 22 (LSCC).
malignant) and was statistically correlated with the clinicopathological Methods: 10 patients with LSCCs were stained for proliferation (Ki67),
characteristics for all cases and patients’ survival rate in malignant SGTs. hypoxia (Hif-1a), vascularization (CD31), immune cells (CD45) and
Results: HDAC-1, -2, -4 and -6 were abundantly expressed in SGTs, al- scored for keratinization. For Ki67 and Hif-1a, the average coverage of
though their expression was not different between benign, low grade (LG) the tumour islands were scored. For CD31 and CD45, the average cov-
malignant and high grade (HG) malignant SGTs. Increased HDAC-2 and erage of the tumour stroma were scored. Correlations were calculated
HDAC-6 intensity of staining was noted in HG malignant compared to LG using the Spearman Rank test.
malignant and benign SGTs (p = 0.017 and p = 0.028, respectively). HDAC- Results: Vascularization and the amount of immune cells showed a
2 positivity was significantly associated with longer overall survival (OS) of strong positive correlation (r=0,63 p=0,05) in LSCC. Tumour cell prolif-
patients with malignant SGT (p = 0.028). HDAC-2 positivity and absence of eration was strongly positively associated with hypoxia (r=0,58 p=0,08),
HDAC-6 expression were associated with prolonged OS of patients with strongly negatively correlated with vascularization (r=-0,53 p=0,11) and
high-grade malignant SGT (p = 0.003 and p = 0.043, respectively). moderately negatively correlated with the amount of immune cells (r=-
Additionally, high HDAC-2 H-score was significantly associated with longer 0,42 p=0,23). Keratinization and vascularization were strongly positively
OS for HG malignant SGT patients (p = 0.027). associated (r=0,62 p=0,05). Hypoxia and vascularization showed moder-
Conclusion: For patients with malignant SGTs, HDAC-2 expression ate correlation (r=-0,35 p=0,33).
emerges as an important positive prognostic factor whereas HDAC-6 Conclusion: Vascularization showed a positive correlation with immune
expression as negative one. cells. Tumour cell proliferation showed a positive correlation with hyp-
oxia and a negative association with the amount of immune cells and
Co-funded by the European Union (ESF) and Greek national funds vascularisation.
through the Operational Program "Human Resources Development,
Education and Lifelong Learning" (project code: 14999). Supported by the Dutch Cancer Society.

PS-03-019 PS-03-021
Immunohistochemistry analysis of PD-L1 expression in head and MUC4 as a potential marker for differentiating MASC and PLGA in
neck cancer minor salivary glands
M. Ramos1, A. Baldion1, D. Suarez1, S. Perdomo1, M. Palau1, A. C. Taverna1, A. Franchi2, M. Santucci1, M. Baněčková3, A. Skalova3, A.
Avello1, A. Hakim1, A. Escallon1, V. Ospina1, P. Beltran1, G. Ucros1, Agaimy4
A. Muñoz1, O. Torres1, P. Rodriguez1 1
Division of Pathological Anatomy, Department of Health Sciences
1
Hospital Universitario Fundacion Santa Fe de Bogota, Colombia University of Florence School of Human Health Sciences, Italy,
2
Department of Translational Research and of New Technologies in
Background & Objectives: Anti-PD-L1 agents have shown potential in Medicine and Surgery, University of Pisa, Italy, 3 Department of
improving survival in head and neck cancer (HNC) patients. However, no Pathology, Charles University, Faculty of Medicine in Plzeň,
standardised measurement for expression of PD-L1 has been defined. Our Czech Republic, 4 Institute of Pathology, University Hospital Erlangen,
objective is to measure PD-L1 expression by immunohistochemistry in Friedrich-Alexander-University Erlangen-Nuernberg, Germany
HNC with different antibodies and scores.
Methods: 38 samples of HNC from the Hospital Universitario Fundacion Background & Objectives: Mammary analogue secretory carcinoma
Santa Fe de Bogotá, a cohort from the InterCHANGE study were used. (MASC) is a low grade salivary gland tumour which occurs both in major
Immunohistochemistry analysis was made with tissue microarrays. and in minor salivary glands. MASC is known for its wide morphologi-
Ventana SP263 and Dako 22C3 antibody assays were used. Positivity cal, architectural and immunohistochemical spectrum, thus it can mimic
of PD-L1 was calculated using the Tumour Proportion Score (TPS) and other salivary gland neoplasms.
Combine Proportion Score (CPS), scores of ≥1 were considered positive. In minor salivary glands, polymorphous (previously called low grade)
Staining intensity was measured, ranging from 1 to 3 crosses. adenocarcinoma (PLGA) shares with MASC some morphological fea-
Conclusion: PD-L1 expression varied according to the antibody and the tures and S100 positivity.
score used. Ventana’s antibody showed a more intense staining, facilitat- We investigated MUC4 expression in PLGA and MASC to establish it as
ing the overall assessment of PD-L1 expression. A larger study sample potential marker in differentiating these two entities.
comparing antibodies and cutoff points is granted to define a standardised Methods: Tumours from 33 patients were analysed, including 11 PLGA and
measure of PD-L1 expression. 22 MASC. Clinical and pathological data were collected (15 male, 18 female;
28-86 years old). Immunohistochemical data for MUC4 and S100 were
evaluated considering both the staining intensity and the percentage of posi-
PS-03-020 tive cells. All MASC underwent ETV6-FISH analysis for confirmation.
Tumour microenvironment characteristics and their correlations in Results: All MASC cases showed moderate (3 cases, 13,6%) to strong
laryngeal squamous cell carcinoma (17 cases, 77,2%) positivity for MUC4, as opposed to none of the PLGA
Virchows Arch

cases. Interestingly, all 5 minor salivary gland MASC expressed MUC4 previously described 22C3 antibody LDT for the BenchMark XT, we
with high intensity. demonstrated high concordance between PD-L1 assessments via the
Conclusion: The results of our study show that MUC4 could be a useful TPS NSCLC compared to PD-L1 IHC 22C3 pharmDx FDA approved
marker in the differential diagnosis between MASC and PLGA, particu- assay. For other cancers, like UC and HNSCC, PD-L1 is evaluated by
larly on limited biopsy material from minor salivary glands and in cases CPS therefore additional studies are needed to establish comparability.
with strongly overlapping morphological features. Methods: As a pilot, we compared the concordance of 45 cases (34 UC
and 11 HNSCC) scored by a single pathologist (GV). Nevertheless, the
final study will include ~120 UC and ~120 HNSCC cases, and scores of
PS-03-022 several pathologists. We used the clinical cutoffs of CPS≥10 or ≥1, for UC
Clinical significance of Ephrin Receptor (EPH)-A1, -A2, -A4 and -A5 and HNSCC, respectively. After obtaining the PD-L1 status using this LDT
expression in salivary gland tumours and the 22C3 pharmDx assay, we analysed the agreement of both assays.
S. Theocharis1, D. Pouloudi1, P. Sarantis1, G. Levidou1,2, N. Tsoukalas1, Results: Using the 22C3 pharmDx assay, 18 and 27 cases were positive
G. Tsourouflis3, E. Dana1, M. Karamouzis4, J. Klijanienko5 and negative, respectively. Using the 22C3 based LDT, 20 and 25 cases
1
First Department of Pathology, Medical School, National and were positive and negative, respectively. Thus, these assays demonstrated
Kapodistrian University of Athens, Greece 2 Department of Pathology, >95% concordance rates (2/45 discordant scores) and interclass correla-
Humanpathologie, Erlangen, Germany, 3 2nd Department of Propedeutic tion coefficient of 0.91 (ICC of UC and HNSCC was 0.94 and 0.83,
Surgery, School of Medicine, National and Kapodistrian University of respectively). Moreover, morphological evaluation showed high similar-
Athens, Greece, 4 Department of Biological Chemistry, Medical School, ity for PD-L1 staining pattern, and dynamic range.
National and Kapodistrian University of Athens, Greece, 5 Department of Conclusion: This preliminary data demonstrated that the 22C3 antibody
Pathology, Institute Curie, Paris, France based LDT on BenchMark XT demonstrated high concordance with
FDA-approved assay. The suggests that this LDT is also applicable to
Background & Objectives: Aberrant expression of different members of UC and HNSCC. A much larger study is currently in progress.
the Eph/ephrin system family, which comprises the Eph receptors (EPHs)
and their ligands (ephrins), has been reported in various malignancies. Funded by Merck & Co, Inc., Kenilworth, NJ, USA.
Aim of our study was to evaluate the clinical significance of EPH-A1, -
A2, -A4 and -A5 expression in salivary gland tumours (SGTs).
Methods: EPH-A1, -A2, -A4 and -A5 protein expression (positivity, PS-03-024
intensity of staining and H-score) was assessed immunohistochemically Pattern of MMP8 expression in gingival biopsy for the diagnosis of
in 58 SGT tissue specimens (36 benign and 22 malignant), of different different types of periodontitis
histological types, and was statistically correlated with the clinicopatho- V. Zakharava1, L. Kazeko2, A. Anfinahenava2, T. Liatkouskaya1,3
1
logical characteristics for all cases and patients’ survival for malignant Belarusian State Medical University, Belarus, 2 BSMU, Belarus, 3
SGTs. Goethe-Institut Minsk, Belarus
Results: EPH-A1, -A2, -A4 and -A5 were highly expressed in both
benign and malignant SGTs. Differences in EPH-A2 H-score were noted Background & Objectives: Periodontal diseases represent a numerous
between benign, low grade (LG) and high grade (HG) malignant SGTs and diverse group of diseases in both clinical and morphological manifes-
(p=0,001). Additionally, higher EPH-A2 H-score was noted in HG com- tations. The lack of clear clinical and radiological signs of diagnosis of
pared with LG malignant SGTs (p=0,015). Marginal difference in cyto- periodontitis establish the relevance of studying biomolecular markers in
plasmic EPH-A4 H-score was noted between with HG and LG malignant determining the prognosis of periodontitis in the early stages of the disease.
SGTs (p=0,053). Increased EPH-A1, -A4 and -A5 H-score was statisti- Objective: To study the features of MMP-8 expression in patients depen-
cally significantly correlated with decreased overall survival (OS) rate in dent upon the type of periodontitis.
patients with malignant SGTs (p = 0.0227, p=0,0226 and p=0,0016, re- Methods: A biopsy of gingival material was analysed from 63 patients with
spectively), while the respective correlation of EPH-A2 H-score was of either rapidly progressive (RPP, n=26), chronic simple (CSP, n=5), or chron-
marginal significance (p = 0.0587). ic complex (CCP, n=29) periodontitis, and a control group (gingivitis only,
Conclusion: EPH-A2 expression was able to discriminate between be- n=3). Morphometric analysis of the MMP-8 expression was performed
nign, LG and HG malignant SGTs. Additionally, high EPH-A1, -A4 and - using Aperio Image Scope v9.0 software. U-test was applied, p<0.05.
A5 expression proved as adverse prognosis indicators for malignant SGT Results: Expression of MMP-8 have occurred in all samples in the form of
patients. cytoplasmic staining of the inflammatory infiltrate cells in both the group of
patients with signs of gingivitis and all forms of periodontitis. The positive
Co-funded by the European Union (ESF) and Greek national funds expression of MMP-8 was greatest in the group of patients with signs of
through the Operational Program "Human Resources Development, gingivitis (2.72%), decreased in various forms of periodontitis RPP group
Education and Lifelong Learning" (project code: 14999). (0.55%), CSP group (1.93%) and was the lowest in the CCP group (0.09%).
In the group of patients with RPP the positivity of MMP-8 expression did
not have statistically significant differences with that in the group of CSP (p
PS-03-023 = 0.87) but was significantly larger than in the CCP group (p = 0.002). The
High concordance of the PD-L1 22C3 antibody LDT protocol on intensity of MMP-8 expression was highest in the groups of patients with
BenchMark XT compared to the PD-L1 IHC 22C3 pharmDx kit signs of gingivitis and CSP and the lowest in the groups of patients with
for urothelial carcinoma (UC) and head and neck squamous cell RPP and CCP who had no significant differences in this indicator.
carcinoma (HNSCC) Conclusion: The results suggest the most a useful indicator for the dif-
G. Vainer1, T. Neuman1, Y. Fellig2, K. Meir2, N. Hirshoren2, O. Gofrit2, ferential diagnosis of RPP with CSP can be considered the positivity of
L. Huang3, J. Juco3, T. Bal3 the MMP-8 expression (which is significantly lower in the CSP group)
1
The Hebrew University - Hadassah medical center, Jerusalem, Israel, with comparable expression intensity between groups, and for CSP group
Israel, 2 Hadassah-Hebrew University Medical Center, Israel, 3 Merck & the intensity of expression (which has significantly higher in the patients
Co., Inc., USA with chronic simple periodontitis) with comparable of the area of the
expression of this marker between groups. The identified features of
Background & Objectives: Pembrolizumab is an anti-PD-1 drug which MMP-8 expression can be used to diagnose and predict the course of
is approved for several indications including UC and HNSCC. Using our periodontitis at the stage of disease manifestation.
 Virchows Arch

using two multiplex (14-plex and 40-plex) magnetic bead-based

Sunday, 8 September 2019, 09:30 - 10:30, Agora 3
RNA expression assay as previously described (Baldacchino et al.,
PS-04 | Molecular Pathology
2018, JOVE).
Results: At diagnosis, 3.5% of breast cancer cases were reported as
PS-04-001 heterogeneous. Nonetheless, on second viewing, 17.5% of cases
Down-regulation of TGFB1 gene expression in patients with colorec- (n=97) were observed heterogeneous by H&E on morphology.
tal cancer in association with primary tumour location and metasta- Similarly, 17% of HER2 positive cases (n=294) showed heteroge-
tic disease neous HER2 staining. Expression profiles were analysed from mul-
E. Aleksandrova1, M. Gulubova2 tiple areas of each primary tumour. Distinct molecular subtypes of
1
Trakia University, Medical Faculty, Stara Zagora, Bulgaria, 2 Trakia breast cancer were identified in 9/23 (39%) cases while 11/23 (48%)
University, Medical Faculty, Department of General and Clinical showed a distinct proliferation rate, using Ki67 and AURKA.
Pathology, Bulgaria Differential expression of Epithelial-Mesenchymal transition
(EMT) markers (8/12, 67%), PP2A complex markers (7/12, 58%)
Background & Objectives: The complex role of the pleiotropic cytokine and vascularisation markers (5/12 42%) were observed within het-
transforming growth factor-beta 1 (TGF-β1) in colorectal cancer (CRC) erogeneous breast cancer.
development and progression has been widely studied. Recently, altered gene Conclusion: Tumour heterogeneity can manifest into distinct morphol-
expression profiles of the TGFB1 gene in CRC patients has been associated ogies characterised by differential expression of genomic, transcriptomic
with poor prognosis and increased metastatic potential. In line with recent and protein biomarkers. With the ever-increasing biomarkers for targeted
findings our aim was to investigate mRNA levels of TGFB1 in patients with therapeutics, identifying heterogeneity effectively will enable combinato-
CRC in association with clinical features of the studied subjects. ry treatments enabling better response.
Methods: A group of 63 CRC patients from the region of Stara Zagora,
Bulgaria were included in the present study. Total RNA, consequently
reverse transcribed to cDNA, was extracted form fresh frozen biopsy PS-04-003
specimens from the tumour and adjacent non-tumoural tissue. Relative Detection of novel HNF1B mRNA splicing variants in selected tissues
mRNA levels were determined with TaqMan-based quantitative real-time M. Bartu1, J. Rosmusová2, J. Kopejsková2, L. Hadravsky2, J. Hojný1, K.
polymerase chain reaction and the results were presented as n-fold mean Němejcová1, I. Tichá1, P. Dundr1
1
difference (RQ-relative quantity) of the target gene relative to calibrator. Institute of Pathology, First Faculty of Medicine, Charles University and
Results: TGFB1 mRNA levels were significantly lower in tumour tissue General University Hospital in Prague, Czech Republic, 2 Institute of
compared to non-tumoural mucosa of the studied subjects (р=0.006, t- Pathology, First Faculty of Medicine, Charles University and General
test). We also observed significant down-regulation of TGFB1 gene in University Hospital in Prague, Czech Republic
tumours located in the colon (dCt mean= 9.00) compared to localization
in the rectum (dCt mean=13.34) or the sigma (dCt mean=12.43), Background & Objectives: Hepatocyte nuclear factor-1-beta (HNF1B)
(p=0.001, ANOVA). Additionally, our results indicated lower gene ex- is a transcription factor crucial for kidney, urogenital tract, pancreas, gas-
pression in cases without distant metastases compared to metastatic cases trointestinal tract and liver development. It’s involvement in cell cycle
(p=0.074, t-test) with mean dCt values 12.63 and 10.04, respectively. regulation and tumourigenesis has yet to be explained. Our aim was to
Conclusion: Our results suggest that down-regulation of TGFB1 in CRC characterise the spectrum of HNF1B mRNA splicing variants across dif-
patients might be a possible mechanism of colorectal carcinogenesis in- ferent tissues for further expression analysis.
volved in the localization and progression of the disease. Methods: RNA (RQN>8.8) isolated from RNAlater stored tissues
(uterine corpus, ovary, large intestine, kidney, pancreas and prostate
This work was financially supported by the National Science Fund, carcinomas, all with paired normal tissues) was subjected to cDNA
Bulgaria, Research grant number KП-06-H23/2 from 17.12.2018. synthesis by SSIII transcriptase and random hexamers. Four random
samples of each tissue type were pooled and analysed using in-house
multiplex PCR (mPCR) of all present exon-exon junctions and NGS
PS-04-002 (Illumina).
Molecular profiling of breast cancer intra-tumour heterogeneity Results: In total, 37/39 of the detected splicing variants were novel. Four
S. Baldacchino1, E. Borg2, J. Scerri3, J. DeGaetano4, C. Saliba5, C. predominant HNF1B transcripts, including two known (3q, Δ7_8) and
Scerri6, P. Schembri Wismayer2, G. Grech1 two novel (Δ7, Δ8) splice variants were detected in all tissue types. In
1
Department of Pathology, University of Malta, 2 Department of high grade serous carcinoma only four predominant transcripts were de-
Anatomy, University of Malta, 3 University of Malta, Department of tected. In other tissue types multiple (14-28) variants were detected. The
Physiology and Biochemistry, University of Malta, 4 Department of data suggests the expression of several tissue-specific transcript variants
Pathology, Mater Dei Hospital, Malta, 5 Centre for Molecular Medicine (e.g. Δ2_6 or Δ5_7), while the remaining variants were detected across
and Biobanking, University of Malta, 6 Department of Physiology and the majority of the analysed tissue types.
Biochemistry, University of Malta Conclusion: The applied mPCR and NGS approach revealed a series of
novel isoforms with unknown functions. The expression profiles of pre-
Background & Objectives: Despite the efficacy of targeted therapy, dominant or tissue specific variants will be analysed to complete the
some HER2 positive breast cancer patients do not respond to trastuzumab splicing pattern across different tissues.
with an 88% 4-year overall survival (n=43). A death rate of 12% persists
at 15 years from diagnosis of patients on tamoxifen for 10 years. Tumour Supported by Ministry of Health, Czech Republic project RVO 64165
heterogeneity is a known mechanism for resistance. Understanding het- and by the AZV17-28404A project.
erogeneity allows for combinatorial targeted therapies to target the dis-
tinct tumour clones and achieve remission.
Methods: Heterogeneous cases were identified by 3 methods in sep- PS-04-004
arate studies: 1) by histopathological report, 2) by morphology from Dual EGFR mutations: five years experience in one center
Haematoxylin & Eosin staining (H&E) and 3) by variation in HER2 E. Bozkurtlar1, H. Kaya1
1
staining. Tumour sampling was performed using laser microdissec- Marmara University School of Medicine, Department of Pathology,
tion or using 0.5mm cores. FFPE samples were lysed and profiled Turkey
Virchows Arch

Background & Objectives: The detection of EGFR mutations of lung K. Cizkova1, Z. Tauber1, K. Koubova1, J. Firic1, J. Ehrmann2
1
cancer predicts the response to EGFR inhibitor therapies. This study was Department of Histology and Embryology, Faculty of Medicine and
conducted to demonstrate our cohort’s frequencies of dual EGFR Dentistry, Palacky University, Olomouc, Czech Republic, 2 Department
mutations. of Clinical and Molecular Pathology & Laboratory of Molecular
Methods: The cases of this study were tested at our center from 2014 to Pathology, Faculty of Medicine and Dentistry, Palacky University,
2019.The cases were examined in Rotor-Gene Q ® , a real time- Olomouc, Czech Republic
PCRcycler, with EASY® EGFRKit.
Results: The EGFR mutation rate was found to be 11,9% among 2138 Background & Objectives: Soluble epoxide hydrolase (sEH) metabo-
cases. The mean age of whole EGFR mutated cohort was 62. The lize active CYP epoxygenase-generated metabolites of arachidonic acid
most common mutations were 58% (N=148 ) on Exon 19del and 27% to less active diols and may play a role in cell differentiation. In intestines,
(N=69) on Exon 21. Fifteen cases (0,7% of 2138 EGFR screened the increase in sEH expression was detected in apical part of villi or on the
cases) had dual mutations of EGFR and, 8 of 15 cases (0,37% of surface epithelium of colon and also in in vitro differentiated HT-29 and
2138 EGFR screened cases) had no previous anti-EGFR therapy his- Caco2 colorectal carcinoma cell lines. The differentiation of absorptive
tory. The distribution of dual EGFR mutations was 2 cases with exon intestinal cells is associated with increase in villin expression which as-
21 and exon 20 T790M, 2 cases with exon 19 and exon 21, 2 cases sures the stability of microvilli of brush border.
with exon 18 and exon 19, 1 case with exon 19 and exon 20 T790M Methods: Undifferentiated, sodium butyrate-differentiated HT-29
and,1 case with exon 18 and exon 21. and spontaneously differentiated Caco2 cell lines were treated by
Conclusion: The frequency of EGFR of our cohort was 11,9%, sim- TPPU (inhibitor of sEH). The expression of villin was measured by
ilar to the Caucasian populations of the previous reports, and, also InCellELISA. The colorectal carcinoma and normal tissue samples
associated with gender (Female/male ratio: 3,8). The most common were obtained from 45 patients in total (both samples from each
EGFR mutations were exon19 del and exon 21, respectively. The patient). Detection of sEH and villin was performed by two-step
frequency of dual EGFR mutations of our untreated cases was immunohistochemical method.
0,37%. We could not reveal any “most common mutation” in our Results: Administration of sEH inhibitor to differentiated HT-29 and
dual EGFR mutation group. Caco2 cell lines led to significant decrease of villin expression in
comparison to control cells. The expression of both, sEH and villin
was significantly decrease in carcinoma samples in comparison to
PS-04-006 normal tissue obtained from the same patient. Moreover, the decrease
CTNNB1 and APC genes mutations analysis in a series of desmoid in sEH and in villin expression in patient samples revealed moderate
tumours positive association.
P. Cervera1, S. Melloul2, Y. Ditchi3, Y. Parc1, T. Andre1, E. Guillerm1, C. Conclusion: Our in vitro data suggest that sEH play an important role in
Colas4, F. Coulet1, J. Flèjou1 differentiation of intestinal cells. This is supported by decrease of sEH
1
APHP Sorbonne Université, France, 2 APHP, France, 3 Hôpital St and villin in tissue samples of patients with colorectal carcinoma.
Joseph, France, 4 Institute Curie, France
The work was supported in part by grants NPS I LO1304 and DRO (UP,
Background & Objectives: Desmoid tumours are slowly proliferating, 61989592) from the Czech Ministry of Education.
non-metastasizing tumours with a highly invasive capacity, which can be
life-threatening in the case of intra-abdominal localization in familial
adenomatous polyposis syndrome (FAP), with a significant risk of recur- PS-04-008
rence. Because of the severe implications arising from the diagnosis of Multi-center evaluation of tissue classification by mass spectrometry
FAP desmoid tumour, it is critically important to distinguish desmoid imaging
tumours in FAP from sporadic desmoid, especially in young patients. S. Deininger1, C. Bollwein2, R. Casadonte3, P. Wandernoth3, K.
According to Knudson’s ‘two-hit’ theory, the occurrence of somatic in- Kriegsmann4, M. Kriegsmann5, T. Boskamp1, J. Kriegsmann3, W.
activation of the APC gene in addition to germline inactivation, is a Weichert2, P. Schirmacher5, A. Ly1, K. Schwamborn2
1
fundamental step in the onset of desmoids. In this study, we explore the Bruker Daltonik GmbH, Bremen, Germany, 2 Technical University of
two-hit theory in a series of FAP desmoids and the occurence of an APC Munich, School of Medicine, Institute of Pathology, Germany, 3 Proteopath
second hit in sporadic CTNNB1 mutated desmoids. GmbH, Germany, 4 University Hospital Heidelberg; Department of
Methods: Sanger sequencing and targeted next generation sequencing Haematology, Oncology and Rheumatology, Germany, 5 University
were performed in a series of paraffin embedded desmoid tumours in Hospital Heidelberg, Institute of Pathology, Germany
86 patients.
Results: 50 (including 20 male) of 86 patients (49 male and 37 fe- Background & Objectives: It is possible to perform tissue phenotyping
male) were diagnosed with a FAP desmoid. It was located in the based on mass spectrometric imaging data. However, comprehensive stud-
abdominal wall or into the peritoneum of the abdominal cavity, and ies assessing the variation across different sites and their impact on tissue
occasionally subcutaneously. 36 were diagnosed with a sporadic classification are largely lacking. Here, we have evaluated how well tissue
desmoid of more ubiquitous location. In all the FAP desmoids, a classification based on Matrix-Assisted-Laser-Desorption/Ionization
second hit APC gene mutation have occurred, with no CTNNB1 (MALDI) mass spectrometric imaging (MSI) can generalize across sites.
mutation. On the contrary, no APC mutation, have occurred in the Methods: A tissue microarray (TMA) comprised of human FFPE sam-
sporadic desmoids. ples representing 6 different tumour entities (leiomyoma, seminoma,
Conclusion: In this desmoid tumours series, CTNNB1 and APC genes mantle cell lymphoma, melanoma, invasive ductal carcinoma of the
mutations are mutually exclusive inferring that highlighting a CTNNB1 breast and squamous cell carcinoma of the lung) was used. These samples
mutation, exclude the diagnosis of FAP desmoid tumour. were prepared for MALDI-MSI and measured at three different sites
using a standard protocol. The baseline performance of the classification
task was evaluated by using cross-validation on the individual TMAs. We
PS-04-007 then evaluated how well a classification model based on data from two
Soluble epoxide hydrolase as an important player in differentiation sites performed on the data of the remaining site.
of intestinal cell: a lesson from cell culture and colorectal carcinoma Results: Selecting the relevant mass features for training the classifier
tissue samples was necessary for performance of classification. Treating the entire cores
 Virchows Arch

as representative for the respective tumour entity, the baseline perfor- Methods: DISH results of 140 breast cancer patients with equivocal (2+)
mance for the classification was an accuracy of 82.6% correct classifica- HER2 immunohistochemical staining at Makati Medical Center from
tions. Accuracy over sites was 74.1%. With detailed histological annota- October 2012 to September 2016 were reviewed. FISH testing was per-
tions the classification accuracy was 92% on the individual TMAs and to formed using dual-color PathVysion HER2 DNA Probe Kit (Abbott
84% accuracy when applied over sites. Molecular, Illinois). FISH and DISH results were categorized according
Conclusion: Initial results indicate that MALDI-MSI can be performed at a to the 2013 ASCO/CAP scoring criteria for in situ hybridization. Overall
level that allows relevant multi-center research studies. MALDI imaging concordance and kappa coefficient were determined.
based tissue classifiers are able to generalize across sites. A detailed histolog- Results: Thirty-eight of 140 DISH results reviewed had available
ical annotation of the tissue improves the performance of the classifiers. paraffin blocks with adequate tumour cells and were therefore sub-
jected to FISH testing. Demographics included 38 females with me-
dian age of 56 years old (range: 19 to 77 years old). Twenty-seven
PS-04-009 (27) cases (71.05%) had higher histologic/ nuclear grades. The me-
A novel method for isolation of tumour and healthy cells from FFPE dian tumour size was 1.9 cm (range: 0.7 to 6.0 cm). Overall concor-
carcinoma samples improves genetic analysis by next-generation dance was 63.16% with kappa coefficient of 0.2267. Both testing
sequencing methods were predominated by nonamplified cases.
M. Delso-Vallejo1, C. Poggel1, R. Hilgers1, J. Gaiser1, J. Soyka1, A. Conclusion: The overall concordance did not fulfil the ASCO/CAP rec-
Bosio1, S. Küffer2, P. Ströbel2, O. Hardt1 ommendation of 95% concordance. The findings are consistent with three
1
Miltenyi Biotec, Germany, 2 Miltenyi Biotec, Germany, 3 Institute of other studies done in the last 5 years. Given the technical advantage of
Pathology, University Medical Center Göttingen, Germany DISH over FISH, further investigation of its correlation with treatment
response in a larger, multicenter cohort is warranted to determine more
Background & Objectives: Vast archives of formalin-fixed paraffin- suitable cut-off values.
embedded (FFPE) samples represent an easily accessible resource in
retrospective large-cohort studies for biomarker or neoantigen iden-
tification in cancer research. Despite the convenient handling and PS-04-013
storage of FFPE samples, there are also some drawbacks to be con- Tumour mutation burden: from recommendations for testing to ex-
sidered. Solid tumours are heterogenous samples composed of both ternal quality assessment schemes
tumour and a non-tumour cells, and proportions of these two cell F. Fenizia1, B. Besse2,3, Z.C. Deans4, E.M. Dequeker5,6,7, M. Horan8, S.
compartments can vary depending on the tumour type, disease stage, Patton 9 , E. Rouleau 10 , E. Torlakovic 11 , N. Wolstenholme 9 , N.
treatment, and other factors. The presence of non-tumour cells intro- Normanno1
1
duces a considerable bias in the molecular analysis of bulk FFPE Istituto Nazionale Tumouri "Fondazione Giovanni Pascale", IRCCS,
samples. Therefore, enrichment of tumour cells prior molecular anal- Naples, Italy, 2 Department of Cancer Medicine, Gustave Roussy,
ysis is critical to obtain reliable results. Villejuif, France, 3 Paris-Sud University, Orsay, France, 4 UK NEQAS
Methods: We present a fully automated protocol for the dissociation of for Molecular Genetics, Department of Laboratory Medicine, Royal
FFPE samples that enables subsequent isolation of tumour and non- Infirmary of Edinburgh, Little France Crescent, United Kingdom,
5
tumour cells from carcinomas, based on the expression of cytokeratin Biomedical Quality Assurance Research Unit, Department of Public
and vimentin. Dissociation is performed using the new FFPE Tissue Health and Primary Care, KU Leuven, Belgium, 6 University Hospital
Dissociation Kit in combination with the gentleMACS™ Octo UZ Leuven, Departement of Medical Diagnostics, Belgium, 7 European
Dissociator with Heaters. After dissociation, we tested different carcino- Society of Pathology (ESP), Anderlecht, Belgium, 8 RCPAQAP
ma samples for ploidy analysis using flow cytometry, and mutation anal- Molecular Genetics, St. Leonard's, Sydney, Australia, 9 European
ysis by next generation sequencing. Molecular Genetics Quality Network (EMQN), Manchester Centre for
Results: Reliable analysis of the ploidy content of cytokeratin-positive Genomic Medicine, St Mary's Hospital, United Kingdom, 10 Department
carcinoma cells was achieved using vimentin-positive non-tumour cells of Pathology and Medical Biology, Institute Gustave Roussy, Villejuif,
as internal control. Furthermore, automated FFPE dissociation did not France, 11 Department of Pathology and Laboratory Medicine, College of
compromise DNA stability, and isolation of carcinoma cells (>95% pu- Medicine, University of Saskatchewan, and Saskatchewan Health
rity) significantly enriched tumour-specific single nucleotide variants, Authority, Saskatoon, Canada
e.g.: KRAS and TP53 genes.
Conclusion: This new automated protocol for FFPE dissociation allows Background & Objectives: Immune checkpoint inhibitors (ICI) are
the specific isolation of tumour and non-tumour cells to enhance the changing the paradigm of treatment of several tumour types. Tumour
sensitivity of genetic analysis of carcinomas. mutation burden (TMB) has been associated with benefit to ICIs in mul-
tiple cancer types, representing a possible predictive biomarker. TMB
measures the total number of mutations per coding area of a tumour
PS-04-012 genome. Different NGS panels for TMB calculation in clinical practice
Comparison between Fluorescence In Situ Hybridization (FISH) and are under development. Appropriate external quality assessment (EQA)
Dual In Situ Hybridization (DISH) in the determination of HER2 schemes are required to ensure that patients receive a TMB test of ade-
status in breast cancer among Filipinos quate quality.
G.A. Espiritu1, E. dela Fuente2, M. Diwa1 Methods: The International Quality Network for Pathology (IQN Path),
1
Makati Medical Center, Philippines, 2 San Juan de Dios Educational with the endorsement of ESMO, is conducting a project to organize EQA
Foundation Inc. - Hospital, Philippines schemes for the evaluation of TMB in clinical practice. The first part of
the study is the identification of adequate control material. Therefore, ten
Background & Objectives: HER2 monoclonal antibody has been effective formalin-fixed paraffin-embedded tumour cell lines provided from
in the treatment of breast cancer with HER2 overexpression. Fluorescent in SeraCare will be assessed for TMB using different approaches. Five
situ hybridization (FISH) has been used for determination of HER2 amplifi- tumour cell lines will be then chosen to be used as a standard reference
cation in cases of breast cancer with equivocal HER2 expression by immu- material. This reference will be further validated in a pilot EQA scheme
nohistochemistry (IHC). We determined the concordance between FISH and for TMB. Thirty laboratories will be selected to participate in the EQA
a relatively new method, dual in situ hybridization (DISH), in evaluating through a survey that will assess which centres offer TMB testing, their
HER2 status of breast cancers among Filipinos. expertise and the technology used for testing.
Virchows Arch

Results: We will present the results of the survey and the validation of the Methods: In 2017-2019 period, KRAS/NRAS/BRAF somatic mutation
control material performed within the pilot EQA scheme for TMB. analysis was carried in 396 patients with colorectal cancer treated in
Conclusion: The use of TMB as predictive biomarker poses different Lower Silesian Oncology Centre in Wroclaw.
challenges for molecular pathology laboratories. The ESMO-IQNPath Molecular tests were conducted with Idylla System (Biocartis), real-time
project will help harmonize TMB testing in clinical practice. PCR based molecular diagnostics system. The following tests were used:
KRAS 3.0 and NRAS/BRAF 1.0. Quantitative analysis was performed
automatically by algorithm included in the software provided by the
PS-04-014 manufacturer.
Concordance of Ventana SP218 PTEN IHC and CST138G6 PTEN Detailed clinical and pathological data were collected for 172 patients by
IHC assays with known PTEN genetic status in prostate cancer the date the poster was created.
R. Fish1, P. Scorer1, P. Lao-Sirieix2, M. Kockx3, E. de Bruin4, M. Results: Mutations in KRAS gene were detected in 48% (190) patients.
Roudier4, A. Sharp5, B. Ehrhardt5, C. Barker1 NRAS and BRAF genes revealed mutations in 4,8% (19) and 6,6% (26)
1
Precision Medicine Laboratories, Precision Medicine and Genomics, cases, respectively. Non-diagnostic results were obtained in 4% (16)
IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom, cases. The frequency of mutations (as a relative percentage of all mutated
2
Oncology Companion Diagnostics Unit, Precision Medicine and cases) is presented in the table below:
Genomics, IMED Biotech Unit, AstraZeneca, Cambridge, United
Kingdom, 3 HistoGeneX Laboratories, Belgium, 4 Translational
Science, IMED Biotech Unit, AstraZeneca, Cambridge, United Gene Mutation %
Kingdom, 5 Quantitative Biology, Discovery Sciences, IMED Biotech
Unit, AstraZeneca, Cambridge, United Kingdom KRAS KRAS G12D 23,8%
KRAS G12V 20,0%
Background & Objectives: PTEN tumour suppressor is a major inhibitor KRAS G13D 11,5%
of the PI3K pathway, involved in cell growth regulation, and one of the most KRAS G12A 6,0%
commonly altered genes in prostate cancer. PTEN deleterious mutations KRAS G12C 5,1%
occur in 10-70% of surgically resected prostate and over 50% of metastatic KRAS A146P/T/V 4,3%
prostate cancers. This study was undertaken to show inter-reader and inter- KRAS G12S 3,4%
assay agreement between two PTEN immunohistochemistry (IHC) assays in
KRAS Q61H 1,7%
samples from patients with a known PTEN genetic status.
KRAS G12R 1,3%
Methods: 97 prostate biopsy samples, previously sequenced by FMI
(Foundation Medicine Inc) using the FoundationOne CDx Clinical Trial KRAS A59T/E/G 1,3%
Assay, were stained with two different PTEN antibodies, Ventana SP218 KRAS Q61L/R 1,3%
mAb and CST138G6, validated on the Ventana Benchmark XT and KRAS K117N 0,9%
Labvision platforms respectively. Concordance at matched cut-offs were KRAS Q61K 0,4%
analysed between assays and readers, reported and compared with se- NRAS NRAS Q61K 2,1%
quencing data. NRAS Q61R 1,7%
Results: Using two cut offs, H score (<10) and percent tumour staining NRAS G12D 0,9%
(<50%), inter-assay concordance was 92-96%. There was a consistent NRAS G12C 0,9%
and moderate variability between the two PTEN IHC pathologist scoring NRAS G13R/V 0,9%
evaluations with overall percent agreement on PTEN status for each assay
NRAS Q61L 0,9%
of 89-94%. Both IHC assays were capable of aligning PTEN protein loss
with PTEN genetic loss; only 2 of 29 samples with genetic loss consis- NRAS Q61H 0,4%
tently scored as PTEN protein proficient by both IHC assays and both NRAS A146T/V 0,4%
pathologists. BRAF BRAF V600E/D 11,1%
Conclusion: This study showed that Ventana SP218 and CST138G6
IHC assays demonstrated inter-reader and inter-assay agreement.
Both assays were capable of aligning PTEN protein loss with genetic Relationship between frequency of KRAS/NRAS/BRAF mutations and
status. Therefore, IHC could potentially provide a cheap and fast detailed clinical and pathological data (including TNM, histological
assay to identify prostate cancer patients whose tumours are PTEN grade, tumour size, localization of primary tumour and metastases) for
deficient. limited numer of patients was presented in the poster.
Conclusion: The frequency of KRAS/NRAS/BRAF mutations in colo-
rectal cancer from Lower Silesia Region are similar to frequencies report-
PS-04-015 ed by other investigators.
Somatic mutations in KRAS, NRAS and BRAF genes in patients
with colorectal cancer from Lower Silesia Region - a preliminary
report PS-04-016
L. Fulawka1, L. Hajac1, M. Glosna2, D. Michalowska1 NSD2 promotes triple-negative breast cancer cell proliferation, mi-
1
Lower Silesian Oncology Centre, Poland, 2 Wroclaw Medical gration and invasion by inhibiting TIMP3 expression
University, Poland B. Gao1, Y. Li2, Y. Pan3
1
Department of Pathology, Affiliated Hospital of Dali University,
Background & Objectives: Mutational status of KRAS/NRAS/BRAF Yunnan, China, 2 Department of Pathology, College of Basic Medical
in colorectal cancer tumours is associated with the clinical response and Science, Dali University, Yunnan, China, 3 The First Affiliated Hospital
resistance to anti-EGFR mAbs (epidermal growth factor monoclonal an- of Dali University, China
tibodies) such as cetuximab and panitumumab.
Here, we report preliminary results from an ongoing study aimed at mo- Background & Objectives: The triple-negative breast cancer (TNBC) is the
lecular profiling of KRAS, NRAS, BRAF genes. Obtained data were most malignant type of breast cancer. Its pathogenesis and prognosis remain
correlated with clinico-pathological features in colorectal cancer. poor largely due to lack of effective targeted therapy. NSD2 (WHSC1/
 Virchows Arch

MMSET) is a histone methyltransferase, which specifically catalyzes H3K36 function upstream of NSD2, which mediates H3K36 and H4K20
dimethylation (H3K36me2). NSD2 is frequently overexpressed in multiple dimethylationand is associated with active transcription of DNA damage
types of cancer and usually associated with malignant progression of tumours. repair genes, such as XPA and 53BP1. GSK126 could downregulated the
However, the function of NSD2 remains unknown in TNBC. This study expression of NSD2, H3K36me2, H4K20me2, XPA and 53BP1, meanwhile
aimed to explore the role of NSD2 in TNBC. upregulated the expression of γH2AX, a marker of DNA damage. In addition,
Methods: To investigate the role of NSD2 in TNBC cell proliferation, mi- five miRNAs including miR-26a-5p, miR-30c-2-3p, miR-196a-5p, miR-
gration and invasion in vitro, CCK8 assay, wound healing and transwell assay 200c-3p and miR-622, were downregulated in miRNA profiling of DLBCL
were performed in MDA-MB-231 cell line, using a recombinant lentivirus and predicted as regulators of NSD2. GSK126 significantly increased the
expressing NSD2-shRNA. Gene microarray was also performed in cells with expression of miR-26a-5p in U2940 cells. Furthermore, the similar expression
stably knockdown of NSD2 to screen its potential downstream genes. changes of these proteins and miR-26a-5p were observed in 293T cells
Results: Both NSD2 and H3K36me2 expression were significantly decreased transefected with EZH2-shRNA. MiR-26a-5p was demonstrated to bind to
in MDA-MB-231 cell line with stably knockdown of NSD2. NSD2 knock- 3’-UTR of NSD2 gene and negatively regulate NSD2 expression.
down significantly attenuated the proliferation, migration and invasion of Conclusion: Taken together, high expression of EZH2 indirectly upreg-
MDA-MB-231 cells. Among the differentially expressed genes resulted from ulated NSD2 via suppression of miR-26a-5p. These results suggest that
knockdown of NSD2, TIMP3 was one of the upregulated genes, which EZH2-miR-26a-5p-NSD2 axis plays a critical role in the proliferation,
functions as a tumour suppressor. NSD2 knockdown mediated upregulation apoptosis and DNA repair of DLBCL and may represent an attractive
of TIMP3 was also demonstrated by qPCR and western blot analysis. therapeutic target in cancer.
Conclusion: NSD2 may work as a novel repression of TIMP3 and
inhibiting NSD2 expression suppressed the proliferation, migration and Supported by National Natural Science Foundation of China (No.
invasion of TNBC cells by increasing TIMP3 expression, suggesting that 81660037), Applied Basic Research Project of Yunnan Province (No.
NSD2 may be a potential therapeutic target of TNBC. 2016FD072), Key Laboratory Project in Universities of Yunnan Province.

National Natural Science Foundation of China (No. 81660037), Applied

Basic Research Project of Yunnan Province (No. 2016FD072), Key PS-04-018
Laboratory Project in Universities of Yunnan Province. KRAS/NRAS and BRAF molecular characterisation through Next-
Generation Sequencing (NGS) techniques in colorectal cancer
M. Gonzalez Farre1, M.C. Fernández Rodríguez1, L. Masfarre2, G.M.
PS-04-017 Parini1, N. Navarro2, E. Moragón1, G. Piquer1, R. Rueda1, J. Gimeno1,
EZH2-miR-26a-5p-NSD2 axis contributes to cell proliferation and D. Naranjo-Hans1, B. Bellosillo1, B. Lloveras3, M. Iglesias1
1
DNA repair and inhibit cell apoptosis in diffuse large B-cell Pathology Department, Hospital del Mar, Spain, 2 Oncology
lymphoma Department, Hospital del Mar, Spain, 3 Hospital del Mar, Spain
Y. Pan1, B. Gao2, Y. Li3
1
The First Affiliated Hospital of Dali University, China, 2 Department of Background & Objectives: Evidence supports testing BRAF (V600) and
Pathology, Affiliated Hospital of Dali University, Yunnan, China, KRAS, NRAS (exons 2, 3 and 4) mutations in colorectal cancers (CRC), since
3
Department of Pathology, College of Basic Medical Science, Dali they provide prognostic and clinically actionable information for targeted
University, Yunnan, China therapy with anti-EGFR monoclonal antibodies. Several reference molecular
tests and Next-generation sequencing (NGS) techniques are used.
Background & Objectives: Diffuse large B-cell lymphoma (DLBCL) is Methods: From January 2018 to March 2019, the analysis of KRAS/
the most common type of non-Hodgkin's lymphoma in adults with diverse NRAS/BRAF was performed through KRAS RGQ PCR, Therascreen
biological and clinicopathological features. EZH2 and NSD2 (WHSC1/ RAS Pyro Extension and Therascreen BRAF Pyro (QIAgen®) in 22
MMSET) are histone methyltransferases (HMTases) involving in the reg- CRC cases and through KRAS mutation kit and NRAS-BRAF mutation
ulation of gene expression and oncogenesis. It has been reported that kit (Idylla, Biocartis®) in 51. All the cases were studied through the NGS
EZH2-NSD2 HMTase axis is coordinated by a microRNA network. Oncomine Solid Tumour DNA panel (Ion Torrent, Thermo Fisher®),
However, the relationship between them in DLBCL has not been fully covering hotspot regions in 22 genes.
elucidated. The current study aimed to assess the expression of EZH2 and Results: Among the 73 cases, KRAS, NRAS (exons 2, 3 and 4) and BRAF
NSD2 and further explore the potential regulatory mechanism in DLBCL. (V600) mutations were detected in 54 (73.97%) patients and 18 were
Methods: In this study, we performed immunohistochemical analysis to wild-type for these positions. All the mutations observed by the reference
explore the expression pattern of EZH2 and NSD2 in 105 cases of tests were also detected by NGS (VAF 1.3-71.1%). Nevertheless, 4 more
DLBCL. U2940 cells were treated with different concentrations of cases (6.15%) with infrequent mutations of KRAS (exon 2) were detected
GSK126, a selective inhibitor of EZH2, and then cell proliferation was only by NGS because these specific mutations are not included with the
assessed by CCK8 assay and soft agar colony formation assay. Cell cycle reference tests. Additionally, mutations in other genes were detected in 58
and cell apoptosis were analysed by flow cytometry. EZH2, NSD2, his- cases (79,45%), predominantly in TP53, PIK3CA and SMAD4.
tone methylation levels and DNA repair proteins were detected by west- Conclusion: NGS allowed the detection of all the variants detected by the
ern blot analysis. MiRNA array in DLBCL, bioinformatic analysis and reference methods (based in qPCR/pyrosequencing). Nevertheless, 4 infre-
qPCR were performed to identify miRNAs by which EZH2-NSD2 axis is quent mutations in the KRAS gen were found in positions not covered by the
coordinated. EZH2-miRNA-NSD2 axis was verified in 293T cells reference tests, as well as additional mutations in other genes with potential
transfected with EZH2-shRNA. Dual luciferase reporter assay was per- implication for the clinical therapeutic management of these patients.
formed to confirm whether NSD2 is the target gene of identified miRNA.
Results: Both EZH2 and NSD2 were highly expressed and positively corre-
lated with each other in DLBCL. Aberrant expression of EZH2 and NSD2 PS-04-019
were also correlated with high level of Ki-67 proliferation index. Suppressing Inflammation slightly increases PCA3 which does not affect its contribu-
EZH2 activity using GSK126 resulted in inhibition of cell viability and colony tion to the refinement of prostate biopsy decision making in combination
formation of U2940 cells in a dose- and time- dependent manner. GSK126 with percentage of free PSA, AMACR, EPCAM and PSGR
also inhibited DNA synthesis, blocked cell cycle in G0/G1 phase, and induced Z. Huskova1, J. Knillova1, M. Kral2, Z. Kolar3, J. Bouchal4
1
cell apoptosis. EZH2, which mediates histone H3K27 trimethylation and is Palacky University, Czech Republic, 2 Department of Urology, Faculty
associated with gene silencing, was shown to be coordinately expressed and Hospital in Olomouc, Czech Republic, 3 Department of Clinical and
Virchows Arch

Molecular Pathology, Palacky University and University Hospital Olomouc, most important irreversible changes having a remarkable altered proteins
Czech Republic, 4 Department of Clinical and Molecular Pathology, Faculty signature. These proteins with an altered expression could be proposed as
of Medicine and Dentistry, Olomouc, Czech Republic possible progression biomarkers.

Background & Objectives: Urinary biomarkers may help urologists to Funding from the MIUR: FIRB 2007 (RBRN07BMCT_11), FAR 2014–
make decisions for the diagnosis of prostate cancer (PCa). In this study, 2018; and in part by Fondazione Gigi & Pupa Ferrari Onlus.
we aimed to validate a panel of urine markers, %free PSA and inflam-
mation in the cohort of PSA dilemma patients.
Methods: In the main cohort of 299 men, we tested the quadruplex PS-04-021
transcripts (AMACR, PCA3, TRPM8, MSMB). In a smaller cohort of Fast immunofluorescence multiplexing using a microfluidic precision
146 men, we also analysed additional transcripts (CD45, EpCAM, EZH2, autostainer and tyramide signal amplification
Ki67, PA2G4, PSGR, RHOA, TBP). After the prostate massage, the urine A. Kehren1, S. Adnane1, B. Pelz1, S. Brajkovic1, C. Hoyt2, D. Dupouy1
1
was collected, RNA isolated, qRT-PCR performed. The results were sta- Lunaphore Technologies SA, Switzerland, 2 Akoya Biosciences, USA
tistically processed with respect to the clinico-pathological parameters.
Results: Expressions of AMACR, PCA3, TRPM8 and EZH2, as well as Background & Objectives: Immuno-oncology and targeted molecular
%free PSA, were statistically different between BPH and CaP (p values therapies have acquired a central role in the treatment of multiple cancers.
0.045, 0.004, 0.005, 0.019 and 0.003, respectively). The best combined mod- Consequently, high-throughput biomarker analysis and tumour immune
el (%free PSA plus PCA3 and AMACR) achieved AUC 0.728 in the main profiling have seen an increased demand. Multiplexed immuno-assays
cohort. In the subset of patients, the best AUC 0.753 was achieved for com- are a powerful tool to address these needs, but still time- and resource-
bination of PCA3, %free PSA, EPCAM and PSGR. Ct values of KLK3 consuming. Our goal is to develop a fast and automated high-plex fluo-
strongly correlated with Ct values of other genes which play a role in prostate rescent immunostaining procedure, using a microfluidic-based device,
cancer (i.e. PCA3, AMACR, TRPM8, MSMB and PSGR). PCA3 (p=0.041) that can be easily implemented as routine assay.
and serum PSA (p=0.005) were increased in patients with inflammation. Methods: Tissue samples are formalin-fixed paraffin embedded (FFPE)
Conclusion: The percentage free PSA and urinary markers distinguish sections of human tonsil. Slides are manually deparaffinized before being
prostate cancer from benign hyperplasia and contribute to a more accurate entirely processed (antigen-retrieval, staining, elution and counterstaining)
indication for prostate biopsy. by Lunaphore’s autostainer, LabSatTM. The OPALTM tyramide signal am-
plification (TSA) system is used as detection method. Signal analysis is done
The study was supported by grant NV15-28628A and DRO: on MantraTM workstation. The 6-plex panel entails FoxP3, PD-L1, PD-1,
FNOL00098892 from the Czech Ministry of Health. CD68, CD8 and pan-CK, plus DAPI counterstaining.
Results: Our platform allowed to reduce drastically the incubation times
due to active transport of reagents across the tissue. Thereby, the auto-
PS-04-020 mated 6-plex assay could be performed in less than 4h30min. Protocol
Discovering triggers of IgA nephropathy progression by Matrix- optimization resulted in high signal-to-background ratio for each marker,
assisted laser desorption/ionisation mass spectrometry imaging and removal of previous step antibodies over 99%. LabSatTM also guar-
M. Ivanova1, O. Dyadyk2, A. Smith1, F. Magni1 anteed remarkable signal uniformity, even over large tissue sections.
1
Università Milano-Bicoccà, Milan, Italy, 2 P.L. Shupyk National Conclusion: LabSat autostainer enables 6-plex multistaining runs in a
Medical Academy of Postgraduate Education (NMAPE), Kiev, Ukraine timely manner, opening the perspective of including tumour microenvi-
ronment screening in routine diagnostics. Moreover, the control over
Background & Objectives: IgA nephropathy (IgAN) is one of the most staining parameters provided by the microfluidic technology delivers
diffuse mesangioproliferative glomerulonephritis (MPGN) worldwide. high-quality results and very good reproducibility. We believe that our
The disease is well known for its multifaceted clinical nature and has platform, combined with the OPAL TSA detection system, could pave the
many issues on predicting the outcome. The ongoing research of prog- way for fast quantitative multiplexed biomarker analysis.
nose predicting biomarkers is being reported. Matrix-assisted laser
desorption/ionization mass spectrometry imaging (MALDI-MSI) is a
proteomics technique used for biomarker discovery directly on-tissue. PS-04-022
Therefore, MALDI-MSI was used to investigate the molecular profile A comparative study of "PD-L1-CAD-test" (BIOCAD) and "PD-L1
of IgAN to reveal proteins related to disease progression. IHC 22C3 pharmDx Kit" (Dako)
Methods: Kidney biopsies of 14 patients were enrolled with previously G. Frank1, O. Kuznetsova1, L. Zavalishina1, Y. Andreeva1, L. Moskvina1
1
histopathologically confirmed diagnosis of IgAN and MPGN. Patients in Fsbei Fpe Rmacpe Moh Russia
both groups were divided into three categories (mild, moderate and ad-
vanced) based on stage of chronic kidney disease (CKD). MALDI-MSI Background & Objectives: A comparative study of the concordance of
analysis were performed on all bioptic tissues with following histological detection PD-L1 expression by «PD-L1-CAD-test» (BIOCAD) FCC
staining of the same sample for signal co-localisation. The average mo- (Federal Service for Surveillance in Healthcare) Approved in Russia)
lecular profiles of IgAN and MPGN biopsies were obtained, compared to and PD-L1 IHC 22C3 pharmDx Kit (Dako) FDA Approved/FSS
each other altogether and separately in each group. Approved in Russia) in Non Small Cell Lung Carcinoma.
Results: 14 discriminative peaks that distinguish IgAN average molecu- Methods: 30 tissue samples of NSCLC were retrospectively collected. Cell
lar profile from MPGN were putatively identified. lines and positive control (tonsil) were used for control staining. PD-L1
All MPGN patients had similar proteomic profile independently from the expression was studied at the same sections using BIOCAD test and Dako
CKD stage while differences were observed between mild versus test with Avtosteiner Link 48. Each section was stained twice in 10 days for
moderate/advanced IgAN. indentifying intralaboratory concordance. Staining of tumour and immune
No differences were noticed between mild IgAN versus mild/moderate cells was assessed. PD-L1 status was considered positive in the case of full or
MPGN. partial staining 1% or more tumour cells with any expression intensity.
Conclusion: IgAN, characterised by more aggressive course, shows dif- Results: Results were concordant in 100% of cases either for control and
ferent proteomic signature for moderate/advanced versus mild stage and for diagnostic staining NSCLC (κ, 0.70; 95% confidence interval, 0.48-
minimal difference for advanced versus moderate stage IgAN patients. 0.96). In 3 samples the number of positive immune cells was less with
Therefore, the moderate stage of IgAN could be considered the point of «PD-L1-CAD-test», but not more than 10%. In 4 cases the low intensity
 Virchows Arch

of reaction with "PD-L1-CAD-test" was detected. The concordance of the Results: Immunocytochemical detection of PDZ and LIM domain protein 4
tumour status after 10 days for both control materials and NSCLC sam- showed changes in its expression in both cell lines when treated and untreated
ples was 100% (κ, 0.70; 95% confidence interval, 0.48-0.96). samples were compared. This finding corresponds to the result of PDLIM4
Conclusion: The concordance of PD-L1 status with «PD-L1-CAD-test» gene methylation status and correlates with both expression and methylation
(BIOCAD) and «PD-L1 IHC 22C3 pharmDx Kit» (Dako) was 100%. So, analysis. Talking about CDKN2B, no methylation of this gene was detected
the «PD-L1-CAD-test» (BIOCAD) can be used in routine practice to in both cell lines. This fact was confirmed by the ICC analysis as well.
determine PD-L1 status in NSCLC according to statistical criteria Conclusion: Protein expression in myeloma cell lines is usually detected
by the time consuming ELISA method, however our study shows a high
functionality of much more faster ICC staining. Here, ICC could serve as
PS-04-024 an effective tool for assessment of the methylation status of selected
Elevated TCRB repertoire convergence and clonal expansion in the genes. Of course, further experiments are necessary to obtain useful in-
NSCLC tumour microenvironment of responders to anti-PD-1 formation about demethylation effect of epigenetic modulators which
monotherapy might be used for multiple myeloma treatment in the future.
K. Leonards1, I. Alborelli1, T. Looney2, L. Quagliata2, P.M. Jermann1
1
University of Basel, Switzerland, 2 Thermo Fisher Scientific, USA Supported by NV18-03-00500 from the Ministry of Health of the
Czech Republic and LF_2019_001 from Palacky University Olomouc.
Background & Objectives: There is an outstanding need to identify
predictive biomarkers for response to anti-PD-1 monotherapy for
NSCLC. Here we investigated TCRB clonal expansion and TCR conver- PS-04-026
gence within the pretreatment tumour microenvironment as predictors of Silencing of E-cadherin in colorectal cancer cells changes their sensi-
response. For context, we compared the predictive value of these features tivity to chemotherapy
with TMB values from the same tumours. M. Manethova1,2, J. Soukup1,2, V. Skarkova3
1
Methods: Total RNA from FFPE-preserved pretreatment NSCLC biopsies The Fingerland Department of Pathology, University Hospital Hradec
(11 responders, 14 non-responders) was extracted for TCRB repertoire se- Kralove, Czech Republic, 2 Charles University Faculty of Medicine in
quencing via the Oncomine TCRB-SR assay (15-265ng RNA input; average Hradec Kralove, Czech Republic, 3 Faculty of Medicine in Hradec
164ng) and the Ion Torrent Gene Studio S5. TMB values were obtained from Kralove, Charles University, Czech Republic
FFPE-preserved gDNA from the same biopsies using the Oncomine Tumour
Mutation Burden Assay. TCR convergence and clonal expansion were eval- Background & objectives: Colorectal carcinoma (CRC) is a malignant
uated independently or in a combined model as predictors of response. tumour with high incidence in developed countries. The treatment con-
Results: TCRB sequencing revealed increased TCR convergence (p = .02, sists usually of multimodal approach including chemotherapy. Several
Wilcoxon) and clonal expansion (p = .06, Wilcoxon) in those who benefited factors including epithelial-mesenchymal transition may play the role in
from anti-PD-1 therapy. A logistic regression classifier combining both the development of chemoresistance during the treatment. We tried to
features was able to discriminate responders from non-responders with a elucidate the role of E-cadherin in the development of chemotherapy
sensitivity of .91 and specificity of .71 at the optimal cutoff, per the resistance in colon cancer cells, especially with drug sensitivity to
Youden’s J method. The TCR-based classifier was able to identify re- irinotecan (IT) and oxaliplatin (OPT).
sponders who otherwise had low to intermediate (<10muts per Mb) TMB. Methods: The effect of IT and OPT on the cell proliferation using WST-1
Conclusion: TCRB clonal expansion and convergence warrant further analysis were compared and IC50 values were determined in colon cancer
evaluation as potential predictive biomarkers of response. Importantly, cell line SW480 and its E-cadherin silencing variant (SW480/siCDH1)
TCRB sequencing may allow for identification of responders who are and in two primary cell lines 47B and 48B obtained from two patients
otherwise missed by TMB-based stratification. who underwent surgery for CRC. The mRNA and protein level were
studied using RT-PCR and western blot analysis. Simultaneously, metab-
olism of IT and OPT was evaluated using LC-MS analysis.
PS-04-025 Results: The viability was significantly reduced after IT/OPT treat-
Immunocytochemical detection of selected proteins in myeloma cells ment in all tested cell lines. Higher expression of mesenchymal
after their treatment with epigenetic modulators markers was detected in SW480/siCDH1 cells together with increased
P. Luzna1, K. Cizkova1, Z. Kolar1, K. Smesny Trtkova1 intracellular accumulation of IT/OPT compared to SW480 cells.
1
Faculty of Medicine and Dentistry, Palacky University Olomouc, SW480/siCDH1 cells were more sensitive to IT/OPT, compared to
Czech Republic SW480 cells. Conversely, mesenchymal markers were highly
expressed in primary CRC cells 47B, compared to 48B cells, but
Background & Objectives: Tumour suppressor or cell cycle regulating higher accumulation of IT/OPT and higher sensitivity to IT/OPT were
genes, which may play important role in multiple myeloma pathogenesis, detected in 48B cells compared to 47B cells.
are often aberrantly methylated. Methylation of these genes can be Conclusion: In SW480/siCDH1 cells accumulated higher amount of IT
followed by loss of their function. The aim of our study was to analyse and OPT and were more sensitive to both treatments, even if the mesen-
the methylation status of CDKN2B (protein p15) and PDLIM4 (PDZ and chymal markers were expressed significantly, compared to SW480 cells.
LIM domain protein 4) tumour suppressor genes in 2 myeloma cell lines On the other hand, cells expressing mesenchymal markers were more
treated with 3 selected epigenetic modulators and to detect possible resistant to IT and OPT treatment and accumulated lower amount of IT
changes of these genes at their protein level by immunocytochemistry and OPT, compared to cells with retained epithelial phenotype.
(ICC).
Methods: Two multiple myeloma cell lines (RPMI 8226, U266) were This work was supported by the Grant agency of Czech Republic [project
treated with 3 epigenetic modulators: Decitabine, Suberohydroxamic No. 17-10331S].
Acid and Disulfiram (all in various concentrations). After 48 hours,
RNA and DNA were isolated and quantitative real-time PCR and meth-
ylation analysis (methylation-specific PCR and pyrosequencing) were PS-04-027
done. Further, portion of the treated cells was spread on glass slides and Acquired resistance mechanisms to EGFR tyrosine kinase inhibitors
two-step immunocytochemical detection of 2 desired proteins was in lung cancer: coexistence of T790M with phenotypic small cell
performed. transformation
Virchows Arch

J. Martin Lopez1, P. Martin Acosta1, E. Tejerina Gonzalez1, D. Garcia 0.56 and 0.53, respectively) or with metastasis to lymph nodes (Rs 0.56 and
Fresnadillo1, Y. Vicente Lago1, L. Martín1, M. Exposito Alcaide1, C. 0.37, respectively). Confocal microscopy revealed colocalization of Skp2
Salas Anton1 and Slug in prostate cancer cells. Chemical inhibition of Skp2 by
1
Department of Pathology. Hospital Universitario Puerta de Hierro, MLN4924 upregulated p27 and decreased Slug expression which supports
Spain a possible link between Skp2 and Slug proteins.
Conclusion: Immunohistochemistry, colocalization studies and in-vitro
Background & Objectives: Patients with non-small cell lung cancer experiments support association between Skp2 and Slug in aggressive
(NSCLC) and epidermal growth factor receptor (EGFR) activating mu- prostate cancer.
tation can obtain significant tumour regression with EGFR tyrosine ki-
nase inhibitors (TKIs). The study was supported by grants NV15-28628A and DRO:
Several mechanisms of acquired resistance to EGFR TKIs have been FNOL00098892 from the Czech Ministry of Health.
reported: secondary mutations in EGFR, a by-pass tracks activation of
EGFR, phenotypic tumour transformation and additional genetic alter-
ations together with EGFR mutation. PS-04-029
Methods: We present a case of EGFR-mutated lung adenocarcinoma Validation of a highly sensitive real-time PCR assay for detecting
(ADC) with two acquired mechanisms of resistance to EGFR TKIs. EGFR T790M mutation in liquid biopsy samples
Results: A 50-year old female with stage IV lung adenocarcinoma M. Novy1, I. Ticha 2, M. Vocka3, K. Gesson1, L. Petruzelka3, C.
(T2bN3M1b) activating EGFR mutation (exon 19 deletion) treated with Oberkanins1
1
TKIs. After initial response to treatment for almost 2 years, radiologic studies ViennaLab Diagnostics, Vienna, Austria, 2 Institute of Pathology, First
demonstrated progression with new histological samples demonstrating an Faculty of Medicine, Charles University and General University Hospital,
adenocarcinoma with T790M mutation. MET amplification was not found. Prague, Czech Republic, 3 Department of Oncology, First Faculty of
After 9 months with second generation TKIs in cytological and histolog- Medicine, Charles University and General University Hospital, Prague,
ical samples, we observed transformation to small-cell lung carcinoma Czech Republic
(SCLC) validated with morphology and confirmed by immunohisto-
chemistry (TTF1+, CD56+, synaptophysin+, Ki67 index: 90%). Small Background & Objectives: Epidermal growth factor receptor (EGFR)
cell histology was not found in pre-resistance samples, which show con- mutations are found in 10-30% of non-small-cell lung cancer (NSCLC)
ventional adenocarcinoma morphology. On a second reevaluation, 6 patients. Patients with activating EGFR mutations usually benefit from
months later, we obtained new samples with combination of adenocarci- tyrosine kinase inhibitor (TKI) therapy, but 50% of patients acquire re-
noma and SCLC and the same molecular alterations. sistance due to the T790M mutation. Osimertinib has recently been ap-
Conclusion: Histologic transformation into SCLC has been described as one proved to treat T790M-positive NSCLC patients.
of the resistance mechanisms to EGFR TKIs. Recognition of small cell car- Methods: We have developed a Taqman-based real-time PCR
cinoma transformation in acquired resistance samples is critical because this ("RealFast") assay for the detection of EGFR c.2369C>T (p.T790M)
probably requires a switch into other chemotherapy regimens. In some cases, along with an endogenous control and including EGFR wild-type sup-
this phenotypic transformation occurred in addition to another mechanisms of pressor to facilitate mutant-enriched PCR. Eighty-six samples, including
resistance such in the current case where two alterations were involved. cfDNA from NSCLC patients and healthy donors, from EQA trials, com-
mercial cfDNA reference standards, as well as NCI-H1975 cell line DNA
and cloned T790M DNA spiked into wild-type DNA, have been analysed
PS-04-028 in two laboratories to validate assay perfomance.
Colocalization of Skp2 and Slug proteins and their possible interac- Results: Out of 31 samples known to be positive for c.2369C>T, the
tion in aggressive prostate cancer RealFast assay detected 30 correctly. Mutation detection failed in one
A. Mičková1, G. Kharaishvili2, M. Kral3, M. Gachechiladze1, M. cfDNA reference sample due to low amount (0.1% in 5 ng) of template.
Mistrik4, J. Bouchal5 Out of 54 negative samples, one positive result was obtained with the
1
Department of Clinical and Molecular Pathology, Palacky University RealFast assay. For one NSCLC sample no confirmed EGFR status was
and University Hospital, Olomouc, Czech Republic, 2 Department of available. A sensitivity of 96.8% and a specificity of 98.2% were calcu-
Clinical and Molecular Pathology, Faculty Hospital in Olomouc, lated. The RealFast assay is capable of detecting 8 copies of c.2369C>T
Czech Republic, 3 Department of Urology, Faculty Hospital in DNA in a minimum of 2.5 ng cfDNA.
Olomouc, Czech Republic, 4 Laboratory of Genome Integrity, Institute Conclusion: The highly sensitive detection of mutated EGFR in low
of Molecular and Translational Medicine, Palacky University, Olomouc, amounts of cfDNA make the EGFR T790M RealFast assay a useful tool
Czech Republic, 5 Department of Clinical and Molecular Pathology, for monitoring the T790M mutation status in liquid biopsy samples of
Faculty of Medicine and Dentistry, Czech Republic NSCLC patients.

Background & Objectives: Skp2 is a substrate recruiting component of

E3 ubiquitin-ligase complex, while Slug is a transcriptional repressor in- PS-04-030
volved in epithelial-mesenchymal transition. Skp2 plays an important role Prostate cancer miRNA profiling in samples from laser capture mi-
in prostate cancer progression, e.g. via recently reported stabilization of crodissection - comparison of two library preparation methods
EZH2 or Twist1, however, relationship with Slug needs further elucidation. K. Okoń1, G. Wątor2, M. Seweryn2, K. Miłek3, A. Piechota-Polańczyk4,
Methods: Prostate cancer patients cohort (N=101) was analysed by im- P. Kapusta2, P. Chłosta5, P. Wołkow2
1
munohistochemistry for the following proteins (Skp2, Slug, AR, Ki-67 Jagiellonian University, Collegium Medicum, Chair of Pathomorphology,
and E-cadherin). Colocalization analysis was performed using Perkin Poland, 2 Jagiellonian University, Medical College, Centre for Medical
Elmer Opal Multiplex kit, Vectra 3.0 imaging system and confocal mi- Genomics - Omicron, Poland, 3 Jagiellonian University, Medical College,
croscope Carl Zeiss LSM 780. Prostate cancer PC3 cells were treated with Chair of Pathomorphology, Poland, 4 Jagiellonian University, Department of
a SCFSkp2 E3 ligase inhibitor MLN4924 and analysed by western blot. Medical Biotechnology, Poland, 5 Jagiellonian University, Medical College,
Results: High Gleason score was significantly associated with higher Skp2 Chair of Urology, Poland
and lower E-cadherin expression (p<0.001 and 0.011, respectively). Skp2
slightly correlated with Slug and AR in the whole cohort (Rs 0.32 and 0.37, Background & Objectives: Prostate cancer is one of the most frequent
respectively), which was enhanced in patients with high Gleason score (Rs cancers in males. This is both overtreated and potentially fatal disease,
 Virchows Arch

thus new prognostic factors are needed. miRNAs are known to participate Conclusion: The next stages of the project are to move to liquid biopsies
in carcinogenesis and are of possible prognostic significance; we current- for both diagnosis and therapeutic monitoring as part of lung and colo-
ly study miRNA expression in prostate cancer in relationship to presence rectal cancer screening programs at University College London Hospital.
of TMPRSS2-ERG translocation. The objective of this preliminary anal-
ysis was to find the best approach to study miRNA expression in laser D. Patel and S. Khan are first authors in equal proportions. The analytical
microdissected prostate cancer samples. This study was supported by a reagents were supported by Agena Bioscience.
grant from National Science Centre, Poland (no. 2015/19/B/NZ5/00044).
Methods: Samples from 3 patients after radical prostatectomies were
subjected to laser microdissection to pick up pure tumour cells and its PS-04-032
stroma. The samples underwent miRNA isolation and NGS library prep- Detection of the mutation burden status and microsatellite instability
arations using 2 commercially available kits. In the first MiSeq run we by targeted next generation sequencing applying a large gene panel
pooled 8 libraries (2 kits per 4 samples from each of 2 patients). In the N. Pfarr 1 , M. Boxberg 1 , K. Riedmann 2 , M. Jesinghaus 1 , B.
second run we pooled 6 samples (single sample of tumour in triplicates). Konukiewitz1, H. Glimm3, P.J. Jost2, S. Fröhling4, W. Weichert5
1
Generated reads were aligned to mirBase 22.1 and counted as well as Institute of Pathology, Technical University Munich, Germany,
2
normalized using miRDeep2 software. Differential expression (DE) was University Hospital rechts der Isar, Germany, 3 National Center for
performed using Bioconductor edgeR, dimension reduction was done Tumour Diseases Dresden, Germany, 4 National Center for Tumour
using the UMAP algorithm. Diseases Heidelberg, Germany, 5 Technical University of Munich, School
Results: We identified several hundreds of miRNA transcripts for each of Medicine, Institute of Pathology, Germany
sample. However, we observed a difference between two kits in the num-
ber of identified transcripts (median 387[266-547] vs 596[488-659], Background & Objectives: Assessing tumour mutation burden in diag-
p=0,0023) as well as their diversity (median entropy 2,921[2,63-3,14] nostic samples might become an important test in routine diagnostics.
vs 3,53 [3,36-3,66]; p=0,00058). DE analysis revealed 271 differentially Currently, exome sequencing is mainly used for TMB but has restrictions
expressed miRNAs between two library preps. Dimension reduction by the time for diagnosis and the limitation of tissue material. Therefore, the
analysis revealed two separate clusters of samples based on the method applicability of applying large gene panels becomes more and more impor-
of preparing the library. The correlation coefficient (between library tant. We applied the Illumina TSO500 panel covering an exonic region of
preps) for samples run in triplicate was only ~0,4. about 1.24 Mb to test the feasibility of targeted next generation sequencing
Conclusion: One of the library preps resulted in a larger number of using formalin-fixed paraffin-embedded tissue for assessing TMB.
identified miRNA as well as more diverse expression profile. This differ- Methods: Assay validation was performed 1) using DNA derived from
ence completely dominated the batch effect of two independent MiSeq known TMBhigh vs. TMBlow samples. 2) Comparison of data from
runs. Overall, our data indicate that it is unacceptable to compare miRNA whole exome sequencing (high vs. low) versus TSO500 from 21 FFPE
gene expression profiles, prepared with different library prep kits. tumour samples. 3) Testing of samples with high PD-L1 expression, high
MSI status or POLE mutation. Sequencing was performed on a
This study was supported by a grant from National Science Centre, NextSeq® system with the NextSeq® 500 hi-Output Kit v2 (300 cycles)
Poland (no. 2015/19/B/NZ5/00044). and 40ng DNA as input. Data analysis was performed using a bioinfor-
matics pipeline (“TSO500 v1.3.0.39“) provided by Illumina with a limit
of detection of 5% allele frequency.
PS-04-031 Results: We confirmed TMB status of all validation samples achieving a
Lung FFPE validation study using the Agena Bioscience concordance of 100%. Furthermore, we were able to confirm the mutation
MassARRAY System with iPLEX chemistry burden status “high” or “low” derived from exome sequencing achieving a
D. Patel1, S. Khan1, M. Gandy2, D. Allen3, M. Rodriguez-Justo4 concordance of 94% between the different approaches. Testing of the samples
1
University College London, United Kingdom, 2 The Doctors from the third phase confirmed a high TMB for the MSI high and the POLE
Laboratory, United Kingdom, 3 Health Services Laboratories, United mutated cases whereas the PD-L1 cases showed only borderline values.
Kingdom, 4 University College London Hospital, United Kingdom Conclusion: In conclusion, data generated by targeted NGS data ap-
proaches can be used to determine TMB and additionally MSI in tumour
Background & Objectives: The purpose of the study was to validate the samples of different entities in high concordance with exome sequencing.
MassARRAY MALDI-TOF Mass spectrometry system for future use with
liquid biopsies enabling cell free DNA detection of somatic mutations for
both diagnosis and disease monitoring. The system core technology was PS-04-033
validated by comparing results from 62 pre-extracted formalin-fixed paraf- Testing the feasibility of tumour mutation burden using the
fin embedded (FFPE) samples that had previously undergone DNA se- Oncomine Tumour Mutation Load Assay - Data from eight sites of
quencing using the IonTorrent next generation sequencer (NGS) to results the Immuno Oncology Consortia
obtained using iPLEX MassArray chemistry from Agena Bioscience. N. Pfarr1, J. Costa2, B. Bellosillo3, F. Fenizia4, W. Dinjens5, I. Alborelli6, C.
Methods: DNA concentration was normalised to 10ng/μL after which Heydt7, M.P. Jansen5, J.C. Machado2, C. Vollbrecht8, S. Merkelbach-Bruse7,
PCR steps were performed using the Agena iPLEX HS Lung Panel which R. van Marion5, M. Hummel8, R. Chaudhary9, C. Allen10, N. Normanno4
1
includes target specific primers for EGFR, BRAF, KRAS, ERBB2 and Institute of Pathology, Technical University Munich, Germany, 2 Institute of
PIK3CA genes. Following the addition of mass-modifying nucleotides, Molecular Pathology and Immunology of the University of Porto (Ipatimup),
samples were arrayed using the MALDI-TOF mass spectrometry system Portugal, 3 Hospital del Mar, Barcelona, Spain, 4 Istituto Nazionale Tumouri
and transferred to an assigned chip where the samples were ionised, "Fondazione Giovanni Pascale", IRCCS, Naples, Italy, 5 Erasmus University
transitioned through a vacuum to the system detector. The time of flight Rotterdam, The Netherlands, 6 University of Basel, Switzerland, 7 Institute of
was measured producing a mass versus charge graphical readout illustrat- Pathology University Hospital of Cologne, Germany, 8 Institute of Pathology,
ing different targets detected within the panel profile. Charite Berlin, Germany, 9 Thermo Fisher Scientific, USA, 10 Thermo Fisher
Results: Increased sensitivity using the iPLEX HS chemistry was ob- Scientific, United Kingdom
served with 55 samples showing matched clinically actionable mutations
across both MassArray and NGS, with six samples harbouring clinically Background & Objectives: Testing the tumour mutation burden
actionable (EGFR, ERBB2, BRAF and KRAS) mutations detected only (TMB) status from formalin fixed paraffin embedded tissue applying
by MassARRAY. exome sequencing is challenging. Oncomine Tumour Mutation Load
Virchows Arch

(TML) Assay is a PCR-based NGS assay analyzing 409 cancer genes PS-04-035
(1.2 Mb exonic region) to assess TMB from low amount of tumour Predictive biomarker analysis of non-small cell lung cancer patients
DNA. Immuno-Oncology Consortia (IOC) gathered eight clinical S. Sakellariou 1 , E.A. Karatrasoglou 1 , I. Chatziandreou 1 , I.
researchers for validating Oncomine TML assay through a three- Giannopoulou 1 , M. Michelli 1 , A. Zougros 1 , E. Rouppou 1 , K.
phase study. Here we present the data from the phase two were Stamopoulos2, A.C. Lazaris1, P. Korkolopoulou1, A. Saetta1
1
FFPE samples with known FMI-TMB were resequenced applying First Department of Pathology, Medical School, National and Kapodistrian
the Oncomine TML assay. University of Athens, Greece, 2 Agii Anargiri General Oncological Hospital
Methods: Six FFPE samples with known FMI-TMB values and clin- of Kifissia, Athens, Greece
ically important variants were provided from one of the eight partner
sites. All sites resequenced these samples applying the Oncomine Background & Objectives: Lung cancer (LC) is the leading cause of
TML assay. Data analysis was performed using the Ion Reporter cancer death worldwide. Many patients have metastatic disease at diagnosis
Software. Statistical analysis was performed to analyse the 1) corre- and prognosis is dismal with 15% 5-year overall survival for all stages.
lation with FMI TMB, 2) reproducibility on FFPE samples and 3) Recently, promising therapies have emerged based on PD-1/PD-L1 immune
Detection of variants found by FMI assay checkpoint inhibitors (ICIs) which have been approved as frontline treatment
Results: Strong correlation above 0.95, except for two sites, was ob- for patients with non-small cell LC (NSCLC).
served between TML-TMB and FMI-TMB. A high reproducibility on Methods: We examined the association between PD-L1 expression and
FFPE samples across all sites with less than 10% CV on > 1 FMI-TMB driver gene mutations (EGFR, KRAS, ROS1) in 326 Greek NSCLC pa-
samples and less than 40% CVon ≤ 10 FMI-TMB samples was observed. tients. PD-L1 immunoexpression using 22C3 PharmDx DAKO monoclo-
Furthermore clinically significant variants from FMI results could be nal antibody (mAb) was defined as high when tumour proportion score
confirmed in TML results with consistent allele frequency across sites (TPS) was ≥50%, low if TPS was 1-49% and absent when TPS was
for all called variants. <1%. EGFR and KRAS mutations were detected by COBAS and
Conclusion: In phase two it could be shown that data generated with the Pyrosequencing, respectively. ROS1 mutations were estimated by immu-
Oncomine TML shows high correlation with TMB data from FMI. nohistochemistry (D4D6 Rabbit mAb) whith positive cases (Hscore≥200)
Furthermore data could be reproduced across the different consortia part- being confirmed by CISH. Data analysis was performed using SPSS v25.0.
ner sites. Results: Our cohort included 261 adenocarcinomas, 40 SCC, 25
NSCLC-NOS (males=228, females=98). Median patient age was 67
years (range 31-96). PD-L1 expression was high in 23%, low in 41.7%
PS-04-034 and negative in 35.3% of cases. EGFR was mutated in 15%, KRAS in
Copy number alterations and somatic mutations in primary and 27.6% and ROS1 in 5% of the cases PD-L1 expression was positively
recurrent BRCA1-associated high-grade serous ovarian carcinomas correlated with KRAS mutations (p =0.018).
G. Raskin1, I. Bizin2, T. Gorodnova2, A. Ivantsov2, E. Imyanitov2, A. Conclusion: PD-L1 expression in NSCLC in Greece is comparable to
Sokolenko2 that reported worldwide. KRAS mutations may affect tumour microenvi-
1
Academic A.M. Granov Scientific Center for Radiology and Surgical ronment and patient's response to immunotherapy. ICIs could represent a
Technology, Russia, 2 N.N. Petrov Institute of Oncology, Russia therapeutic option for KRAS mutant patients. Further investigation into
this notion is warranted.
Background & Objectives: BRCA1-associated ovarian cancers (OC)
represent a specific biological type of tumours characterised by several
molecular features, e.g. near mandatory presence of TP53 mutations and PS-04-036
high level of genomic instability. Here we present the results of whole- Multianalyte testing of FGFR with Modaplex technology
exome analysis of paired (primary and recurrent) OC samples obtained O. Schurat1, M. Luimes2, M. Böhme1, K. Tabiti1
1
from carriers of BRCA1 mutations. Biotype Diagnostic GmbH, Germany, 2 Biotype Diagnostic GmbH,
Methods: 12 samples from six patients were subjected to whole-exome The Netherlands
sequencing. Pattern of somatic mutations and copy number changes were
analysed using GATK software. Global LOH status was rated as LOH-high Background & Objectives: A hallmark of cancer are genetic variations
(>25% loci exhibit LOH) in all samples and remained concordant in both known to be widely involved in the process of carcinogenesis.
primary and recurrent lesions. LOH at BRCA1 locus was seen in all pri- Dysregulation of fibroblast growth factor receptor (FGFR) signalling
mary and five recurrent tumours. TP53 mutations were detected in all cases has been observed in many cancer entities, and reported to have different
and were identical in primary and recurrent lesions from the same patient. meanings depending on tumour type. Here, we describe a novel method,
Results: Frequent gains present in primary and relapsed tumours were the Modaplex technology, which enables simultaneous analysis of mul-
8q24 (MYC) and 3q26 (PIK3CA), whereas gain at 20q13 (SNAI1) was tiple modalities within a single experimental run.
present in four recurrences but only in one primary lesion. Losses of Methods: The Modaplex technology combines and integrates PCR and
genetic material were frequently observed, being concordant at 1p36 Capillary Electrophoresis (CE). During PCR, a femtoliter amount of the
(ARID1A) and 11p15 (RASSF10) and discordant at 10q23 (PTEN) and ongoing reaction is separated by size via CE and the fluorescence of the
16q22 (CDH1). While analyzing the entire spectrum of somatic muta- individual DNA bands is measured. By collecting several data points during
tions, we revealed that only 37% of all mutations observed in recurrent the thermocycling process for each individual band, an amplification curve
tumours were detected in the corresponding primary carcinomas. for each target is recorded, followed by automatic determination of its quan-
Conclusion: Transmission of mutations from primary to recurrent tu- tifying cycle (Cq). The simple assay-development workflow allows for the
mour was rather low and reflect some peculiarities of BRCA1-driven design of various different modality assays, which can be run simultaneously.
tumour's evolution. Paired primary and recurrent ovarian carcinomas Results: We developed a FGFR panel for simultaneous detection of dif-
demonstrate both concordant and discordant somatic events. ferent genetic aberrations. FGFR CNV and FGFR Mutation are assays
Concordant mutations are likely to reflect core events emerged at earlier targeting DNA, while FGFR Gene Expression and FGFR Gene Fusion
stages of OC progression, while discordant alterations may reflect adap- target RNA. Each assay has a midsize complexity and comprises a min-
tation of tumour clones to continuing treatment pressure. imum of six targets. Assays have been verified using artificial and refer-
ence material within a single experimental run.
This work was supported by the Russian Foundation for Basic Research Conclusion: We demonstrated that this technology allows for identi-
[grant 18-29-09090]. fication and quantification of multiple targets per well, the multi-
 Virchows Arch

1
modal potential for the detection of different genetic aberrations in a Emanuel Institute for Biochemical Physics, Russian Academy of
single run and the capacity to process both DNA and RNA based Sciences, Russia, 2 V.I. Kulakov National Medical Research Center of
assays simultaneously. Obstetrics, Gynaecology and Perinatology, Russia, 3 V.L. Talrose Institute
for Energy Problems of Chemical Physics, Russian Academy of
Sciences, Russia
PS-04-037
SERPINA1 up-regulated expression in placental villi in pregnancy- Background & Objectives: Protein misfolding, leading to the accumu-
related complications lation of aggregates, was detected for many pathologies (including car-
V. Sergeeva1, N. Nizyaeva2, N. Starodubtseva2, D. Ivanov3, S. Pekov4, A. diovascular, neurodegenerative and associated with pregnancy).
Bugrova1, O. Baev2, M. Gapaeva2, V. Sinitsyna2, A. Kononihin4, I. Preeclampsia (PE), a severe pathology of pregnancy characterised by
Popov3, V. Frankevich2 arterial hypertension, proteinuria and multiorgan dysfunction, remains
1
Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, the main cause of maternal and perinatal morbidity and mortality. Urine
Russia, 2 V.I. Kulakov National Medical Research Center of Obstetrics, congophilia (a test for the presence of amyloid-like fibrils) is proposed for
Gynaecology and Perinatology, Russia, 3 Moscow Institute of Physics and express diagnostics of pre-eclampsia (Buhimschi IA, et. al. Sci Transl
Technology, Moscow, Russia, 4 V.L. Talrose Institute for Energy Problems of Med. 2014). The aim of the study was to develop an approach for the
Chemical Physics, Russian Academy of Sciences, Russia differential diagnosis of hypertensive complications of pregnancy by uri-
nary peptidome profiling by high-resolution mass spectrometry.
Background & Objectives: Preeclampsia (PE), a multisystem pathologi- Additionally we evaluate protein misfolding both in placenta and urine
cal condition of pregnancy, characterised by arterial hypertension with pro- during preeclampsia.
teinuria, affects 5-8% of pregnancies. The main cause of preeclampsia lies in Methods: Histological(H&E) and immunohistochemical (Ventana
the incomplete transformation of the spiral arteries of the uterus. Previously, Medical Systems, Roche) analysis of 50 placental tissues (20 - PE, 15
fragments of SERPINA1 in urine were proposed as diagnostic and prognos- women with uncomplicated pregnancy, 15 - control) was performed on
tic markers, correlating with PE severity. SERPINA1, the protease inhibitor, the paraffin-embedded slices using Oligomer A11 primary polyclonal
may be synthesized by placenta structures. The aim of the study was to antibodies (1:2000;Invitrogen) and SERPINA1 primary polyclonal anti-
evaluate SERPINA1 expression in placental villi in cases of preeclampsia. bodies (1:500; Invitrogen). The study included 109 women divided into
Additionaly pathological changes in the placenta during pregnancy were groups: preeclampsia (PE), PE superimposed on CAH (chronic hyperten-
visualed by MALDI-imaging mass spectrometry (MALD-MSI). sion), CAH, GAH and control group. Urine samples from each woman
Methods: Histological (H&E) and immunohistochemical analysis were analysed using nano-HPLC-MS/MS and a qualitative analysis by
(Ventana Medical Systems, Roche) of 45 placental tissues (15 women MALDI-MS was performed as previously described (Kononikhin A, et.
with uncomplicated pregnancy, 30 – PE cases) paraffin-embedded slices al. J Proteomics. 2016). Identification and analysis of semi-quantitative
was performed using SERPINA1 primary polyclonal antibodies (1:500; data was carried out using complementary bioinformatics platforms
Invitrogen). Additionally, сryo-slides (12 mkm) were covered with 2,5- (MaxQuant, PEAKS). Protein aggregation in urine was estimated using
dihydroxybenzoic acid by sublimation. MALDI-images were obtained Congo Red test: 2 μl of Congo Red (5 mg/ml) was added to 100 μl of
using Bruker ultrafleXtreme mass spectrometer in positive ion mode. urine, 5 μl of the resulting mixture was applied to a nitrocellulose mem-
Then, MALDI matrix was washed out and slides were stained with H&E. brane (Amersham Protran 0.45NC), dried, scanned, then washed from
Results: SERPINA1 expression in cyto-syncytiotrophoblast, syncytial unbound dye, dried and re-scanned.
knots, decidual cells, amnion, macrophages, stromal cells, endothelium of Results: An approach for a comprehensive analysis of the urine
blood vessels of placental villi, extravillous trophoblast, and in fibrinoid peptidome was developed, which includes sample preparation using ex-
deposits was evaluated. Moreover, expression was significantly higher clusive chromatography, identification of isolated peptides using nano-
(p<0,05) in placental samples in cases of PE, then in control group. HPLC in combination with high resolution mass spectrometry, as well as
Syncytial knots and extravillous trophoblast were surrounded by fibrinoid semi-quantitative and statistical data analysis (Kononikhin A.S., et. al.
deposits predominantly in PE group. A good match between the mass spec- Methods Mol Biol. 2018). Urine peptides were found to be highly spe-
trometric image, built on individual lipid ions, and histological image was cific to the presence/absence of hypertension during pregnancy. A char-
demonstrated. The main ions clearly distinguishing areas corresponding to acteristic panel of peptides, which are fragments of alpha-1-antitrypsin
different structures of the placenta were identified using Mann-Whitney U- (SERPINA1), was revealed for a group of patients with preeclampsia
test (p<0.05). For example, phosphatidylcholines PC 36: 4 and PC 32: 0 (PE, PE superimposed on CAH). Urinary level of protein aggregation
were characteristic for the stem and terminal villi of the chorion. in PE was significantly higher (p<0.01) than in control group and corre-
Conclusion: SERPINA1 upregulation in PE placentas was confirmed. High lated with oligomers and SERPINA1 expression in placenta. Oligomer
SERPINA1 concentration in fibrinoid deposits probably contributes to the A11 and SERPINA1 was significantly higher in placental samples in PE
restriction of trophoblast invasion, reducing the transformation of the spiral cases (cyto- and syncytiotrophoblast, syncytial knots, decidual cells (cy-
arteries of the uterus. A distinct lipid profile of various placental structures toplasm staining), endothelium blood vessels, extravillous trophoblast
allows both visualizing these structures at the molecular level and identifying and fibrinoid deposits) then in other groups.
physiological and pathological changes in the placenta during pregnancy. In Conclusion: An approach for a comprehensive analysis of the urine
particular, abnormal trophoblast invasion leads to ischemia reperfusion inju- peptide was developed, which includes sample preparation using exclu-
ry and accumulation of lipid peroxidation products. sive chromatography, identification of isolated peptides using nano-
HPLC coupled with high resolution mass spectrometry. A panel of pep-
The work was supported by RFBR 18-29-01065 (MALDI-MSI) and by tides was formed, allowing to reliably differentiate hypertensive disorders
the Grant of the President for leading scientific schools (NS-4566.2018.7, in pregnant women. Fragments of alpha-1-antitrypsin confirmed their
075-02-2018-519). significance as markers of preeclampsia. In preeclampsia notable changes
in protein processing with aggregates accumulation in various placental
structures was found. The level of protein oligomers in placenta and urine
PS-04-038 positively correlated.
Protein misfolding in placenta and urine during preeclampsia
V. Sergeeva1, N. Starodubtseva2, K. Muminova2, A. Bugrova1, M. The work was supported by RFBR (#18-315-00435-mol-a, 17-08-01537)
Indeykina 1 , N. Nizyaeva 2 , N. Zakharova 1 , V. Sinitsyna 2 , V. and by the Grant of the President for leading scientific schools (NS-
Frankevich2, Z. Khodzhaeva2, A. Kononihin3 4566.2018.7, 075-02-2018-519).
Virchows Arch

Monday, 9 September 2019, 09:30 - 10:30, Agora 3 manifestation. The localization was: head and neck region (18%), thorax
in (26%), back region (10%), abdominal region (22%) and upper (4%)
PS-05 | Dermatopathology
and lower extremities (16%).
Conclusion: Secondary tumours of the skin are a rare but clinically rel-
evant situation in the histological routine practice. A morphological and
PS-05-001
immunohistochemical correct approach beside a clinical-pathological
Ecrine porocarcinoma: 11 cases in 10 years
correlation (for example to distinguish epidermotropic metastatic mela-
R.I. Bermudez Cameo1, N. Torrecilla Idoipe1, M.J. Viso Soriano1, J.I.
noma from primary melanoma) is mandatory.
Franco1 , H.P. Almanzar Comas1 , S. Bakali Badesa 1, A. Sobrino
Prados1, N. Estrada Mallarino1, A. Arellano Alvarez1, C. Pardillos
Marin2, V. Sanz Salvador1, A.B. Roche Latasa1
1 PS-05-003
Hospital Universitario Miguel Servet Zaragoza, Spain, 2 Hospital Ernest
Primary cutaneous angioplasmocellular hyperplasia- an IgG4 related
LLuch Martin, Calatayud, Zaragoza, Spain
solitary skin lesion? A clinicopathologic study of 5 cases
A.I. Cioroianu1, P.I. Stinga2, C. Popp1, S.A. Zurac1,3
Background & Objectives: Eccrine porocarcinoma (EP) is a very rare 1
Colentina Clinical Hospital, Romania, 2 Colentina University Hospital,
anexial cutaneous tumours. According with some authors, they have an Romania, 3 Carol Davila University of Medicine and Pharmacy, Romania
estimated prevalence between 0,005-0,01% of the total cutaneous tu-
mours. It predominately occurs in elderly people, usually in extremities, Background & Objectives: Primary cutaneous angioplasmocellular
particularly feet and legs. EP may develop de novo or complicate an hyperplasia(pCAPH) is a rarely reported entity (20cases presented
ecrine poroma, chronic lymphatic leukemia, nevus sebaceous and actinic in the literature), being unrecognized by many or considered a non-
lesions. It has been reported a ratio of malignant transformation from specific, reactive phenomena with a yet unrevealed etiopathogenesis
benign poroma to malignant one to be around 18%. According with some by others.
papers, risk factors include exposure of the affected area to trauma, burn- Methods: Five cases of pCAPH met the selection criteria for inclusion in
ing or radiotherapy, immunosuppressive drugs, prolonged exposure to the study-4 males and 1 female,aged20 to 77 years, all presenting with a
ultraviolet light and AIDS. Wide local resection is recommended to pre- solitary skin nodule(size range between 1 and 1,4cm), involving the skin
vent from potential recurrences, because it can reach 20%. of the fingers(n=3),trunk(n=1),inguinal region(n=1). No specific predis-
Methods: Retrospective analysis of diagnosed EP at University Hospital posing factors were present. EVGstain and immunohistochemical
'Miguel Servet' of Zaragoza, between years 2008 to 2018. It has been markers were performed(CD34,CD31,SMA,CD3,CD20,CD38,Kappa
reported 11 cases of the 42.587 skin biopsies (involving the 0,02%). and Lambda light chains,IgG,IgG4,CD117, HHV8) in order to obtain a
Every case was diagnosed by different surgery procedures (punch, shaved complete picture of the entity.
and resection). Results: Microscopic examination of the selected cases showed a
Results: From the total, only 3 cases had morphological features of tran- dermal-based proliferation of small vessels(mostly venules,
sition of ecrine poroma to EP (4%), identifying both histological features scattered capillaries) surrounded by an abundant mixed inflamma-
together. EP has a wide range of age, between 52 to 95 (average of 77), tory infiltrate predominantly composed of non-atypical polyclonal
with a similar prevalence among women and men, 6 men and 5 women. plasma cells, displaying a IgG4/IgG ratio between 30 and60%; a
EP were more frequently located at head and neck (8), follow by thorax- high number of IgG4 plasma cells/HPF was found in each
abdomen (3). None of them had appear at the extremities. None of them case(range between 110 and 390/HPF);B lymphocytes generally
had presented any recurrences after a wide local resection. outnumbered T lymphocytes; in one case was observed a slightly
Conclusion: EP is a very rare tumour, our report had shown some par- increased number of eosinophils; mast cells were frequent(range
ticularities comparing with other references: It represents 0,02% of the between 25 and 73/HPF).All cases were HHV8-negative.
total skin biopsies. It is slightly more prevalent on than women, usually Ulceration of the suprajacent epidermis was detected in 4 cases.
located at head and neck. It has not been observed any recurrences or Other findings like obliterative phlebitis or storiform fibrosis
distant metastasis. It has showed poroma areas in 3 EP. Morphological weren’t identified.
analysis of the skin tumours, cytological and architectural features of Conclusion: Our results were intriguing and raised the possibility of
malignant neoplasia are indispensable to a correct diagnose. including pCAPH on the long list of the conditions that can be associated
with IgG4 tissue plasma cells. An improved understanding of this pecu-
liar entity and of the significance of IgG4 plasma cells rich inflammatory
PS-05-002 infiltrate will require more documented cases.
Secondary tumours of the skin: clinical-pathological aspects focusing
on differential diagnosis *Cioroianu and Stinga are first authors in equal proportion.
C. Cacchi1, A. Rübben2, R.U. Wahl2 This work was supported by a grant of Romanian Ministery of Research
1
Institute for Pathology Uniklinik RWTH-Aachen, Germany, 2 Dermatology and Innovation, CCCDI-UEFISCDI, project number 61PCCDI⁄2018 PN-
Unit Uniklinik RWTH-Aachen, Germany III-P1-1.2-PCCDI-2017-0341, within PNCDI-III.

Background & Objectives: Skin-Metastasis is an uncommon but clini-

cally relevant event; aim of this study is to investigate the incidence and PS-05-004
the characteristics of cutaneous metastasis. Frontal fibrosing alopecia: a clinicopathologic evaluation of eyebrow
Methods: We evaluate the type of malignancy, the localization, the num- hair loss
ber of the metastasis in the skin that were diagnosed in the last 5 years in V. Damaskou1, A.C. Katoulis2, K. Diamanti2, A. Pouliakis1, D. Mortaki2,
our Institution :49 patients (17 and 32 women). We also stress the clinical A. Zacharatou 1 , E. Bozi 2 , N. Koufopoulos 1 , D. Sgouros 2 , I.G.
and histological aspects regarding the differential diagnosis. Panayiotides1
1
Results: We found following metastases :17 melanomas, 12 breast car- 2nd Department of Pathology, National and Kapodistrian University of
cinomas, 8 squamous carcinomas, 2 carcinomas of the ovary, colon (3 Athens, School of Medicine, Attikon University Hospital, Athens,
cases) and lung (1 small cell, 3 adenocarcinomas). The others cases were: Greece, 2 2nd Department of Dermatology and Venereology, National
1 merkel-cell carcinoma, an adenocarcinoma of the oesophagus and one and Kapodistrian University of Athens, School of Medicine, Attikon
adenocarcinoma –NOS. 82% of the cases were single cutaneous University Hospital, Athens, Greece
 Virchows Arch

Background & Objectives: Frontal fibrosing alopecia (FFA) is a form of (such as p53/Rb pathway) close to other neuroendocrine carcinoma in
scarring alopecia leading to frontotemporal hairline recession. Partial or digestive system and other locations.
complete loss of eyebrows is seen in most cases. Our goal was to study
the features of eyebrow involvement.
Methods: We examined specimens from 21 patients with FFA and con- PS-05-007
comitant eyebrow involvement for more than two years; 16 (76%) had Chanarin-Dorfman syndrome with systemic involvement in three
partial, and 5 (24%) complete eyebrow loss. All were females with a siblings
mean age of 65.6±7.3 years. Dermoscopy-guided punch biopsies, from C. Karaoglan1, B. Cayhan2, F. Topaloglu Demir2, Z. Turkoglu2, B. Duz3,
the eyebrow (3 mm, on red or grey dots), were vertically sectioned and N. Buyukbabani1
1
stained with Hematoxylin-Eosin, Masson’s trichrome and Elastica-Van Istanbul Faculty of Medicine, Department of Pathology, Turkey,
2
Gieson stains. Statistical analysis was performed by SAS 9.4 software University of Health Sciences, Haseki Training and Research
using a 5% significance level. Hospital, Division of Dermatology, Turkey, 3 University of Health
Results: Features indicative of permanent hair loss were present in 13 Sciences, Haseki Training and Research Hospital, Division of Medical
eyebrow specimens (62%), whereas preservation of sebaceous glands Genetics, Turkey
was seen in 8 (38%); this finding was associated with neither the onset
nor the clinical degree (partial or complete) of hair loss. We observed a Background & Objectives: Chanarin-Dorfman Syndrome (CDS,
strong correlation (100%, p<0.0001) between the presence of prominent OMIM: 275630) is a rare autosomal recessive disorder of neutral lipid
solar elastosis and absence of sebaceous glands in the eyebrows. metabolism. It is characterised by intracellular accumulation of neutral
Conclusion: Preservation of the sebaceous glands seems to confirm the lipids in cytoplasmic lipid droplets. It involves multiple organs and sys-
clinical and dermoscopic observation that eyebrow loss in FFA may be tems, including skin, liver, skeletal muscle, eyes, ears and central nervous
reversible. Association of prominent solar elastosis with features of seba- system. This condition typically presents with ichtyosiform non-bullous
ceous gland destruction in the eyebrow suggests that actinic damage and erythroderma. Mutations of ABHD5 gene have been determined as the
permanent hair loss may be pathogenetically related. More extensive cause of CDS. Herein, we present three siblings with CDS who have
studies are necessary to confirm our results. congenital ichthyosis and multi-system involvement.
Methods: Hematoxylin and Eosin, Scharlach and Oil Red-O stains were
performed on skin biopsy frozen-sections.
PS-05-005 Results: A 25-year-old woman, her 22-year-old sister and 16-year-old
Analysis of mTOR CXCR4 and PD-1 checkpoint pathways in brother were referred to our Institution with dry skin and hyperpigmented
Merkel cell neuroendocrine carcinomas: correlations with prognosis fine scales present since birth. The patients were put on emollients med-
and viral status ications, but skin scaling was persistent. Dermatological examination
L. Deschamps1, J. Benhamou2, P.E. Sugier3, B. Vergier4, A. Pham- revealed widespread ichthyosis on the facial region, trunk, extensor and
Ledard4, A. Carlotti5, M. Avril5, N. Ortonne6, O. Zehour6, A. Durlach7, flexural regions and scalp in all patients. Physical examination and labo-
F. Grange7, B. Balme8, S. Dalle8, U. Zimmermann9, A. Blom9, M.H. ratory findings showed different degrees of involvement in liver, skeletal
Lorton10, S. Dalac11, A. Couvelard12, E. Maubec2 muscle, eyes and ears in the patients. ADHB5 mutation was detected in
1
Departement of Pathology, France, 2 Bichat APHP Hospital, France, all patients. All skin biopsies showed compact hyperkeratosis, mild
3
INSERM 1018, France, 4 Haut Levêque Hospital, France, 5 Cochin acanthosis and discrete vacuolization of basal keratinocytes, sweat glands
APHP Hospital, France, 6 Henri Mondor APHP hospital, France, 7 and sweat ducts cells. Scharlach and Oil Red-O stains clearly and ele-
CHU Reims, France, 8 Hospices civils Lyon Sud Hospital, France, 9 gantly demonstrated the lipid content of these discrete vacuoles.
Ambroise Parè APHP Hospital, France, 10 CHU Dijon, France, 11 Service Conclusion: CDS is a rare lipid storage disease. It should be considered
de Dermatologie, CHU Dijon, France, 12 APHP- Bichat University Hospital, in patients who have congenital ichthyosis with extracutaneous symp-
France toms. Frozen sections of simple skin biopsy examined by lipid stains
can rapidly and effectively confirm the cytoplasmic lipid storage.
Background & Objectives: Merkel cell carcinoma (MCC) is a rare and
aggressive cutaneous neuroendocrine carcinoma. Our objectives were to
analyse clinicopathological prognostic factors and expression of mole- PS-05-008
cules of 3 main signalling pathways (mTOR, CXCR4 and PD1/PDL1) Proliferative changes of atrophy simulated rat skin after using a
in a large multicenter French retrospective study. vitamine containing ointment
Methods: We collected 153 paraffin-embedded tumours from 144 pa- M. Kostyaeva 1 , I. Kastyro 1 , P. Shmaevskiy 1 , N. Ermakova 1 , Y.
tients. We analysed histological and immunochemical markers on whole Gushchina1, V. Torshin1, S. Ata1
1
slides (Ki-67, CD8, PD-1, PD-L1) or on Tissue Microarrays (CM2B4, Peoples' Friendship University of Russia (RUDN University), Russia
CK20, CHROMOGRANINE A, CD56, SYNAPTOPHYSINE, CXCR4,
SDF-1, pmTOR, 4EBP1, PS6, Rb, p53) Background & Objectives: The use of anti-inflammatory ointments
Results: Metastatic MCC (n= 52) significantly expressed more CXCR4 containing glucocorticosteroids, leads to atrophic skin changes. In this
(p= 0.048) and PD-L1 (p=0.036) as compared to primary tumours. 77% study, we decided to study the reparative properties of the ointment con-
(n=105) of MCC expressing CM2B4 were considered Polyomavirus pos- taining vitamins A, E & D2 (OV), to restore the rat skin after its atrophy
itive. In those MCC-virus positive, we observed less elastosis (p=0.003), caused by the application of hydrocortisone ointment (HO).
ulcerations (p=0.008), cytological atypias (p=0.0068), %Ki-67 Methods: The study was conducted on 24 Wistar rats. Each group included 8
(p=0.00009), alterations of p53 (p=0.008) and Rb (p=0.00009), and more animals: group1 - control, group2 - once a day for 5 days applied 1% HO to
CD8 lymphocytes (p=0.0016) expression and higher PD-L1 (p=0.04). the skin area in the interscapular area, group3 – a dermatotropic drug within 5
The presence of Polyomavirus was correlated with significantly better days afret HO using. OV was applied dermally, daily after the skin atrophy
overall survival (p=0.002). model was formed with HO. H&E stained histological sections of the skin
Conclusion: Our large multicentric study, suggests the potential dual role were studied in group 2 on day 5, and in group3 on day10.
of CXCR4 and PD-L1 in metastatic progression of MCC regardless of Results: HO application in group1 led to thinning of the epidermis to one
viral status, and confirms the importance of the immune reaction in MCC- layer, in control:3–6 cell layers(CL). The stratum corneum was absent, the
virus positive with better overall survival. We highlight that the MCC- cells were flat, mitoses were absent.Hair follicles and sebaceous glands mark-
virus negative display an aggressive phenotype and molecular alterations edly atrophied. In group3 CL number was not only restored, but exceeded the
Virchows Arch

control values(6–9CL). Mitosis was noted in the malpighian&granular improve the quality of the skin before and after in the same group and
CL;spinous layers contained many keratohyaline granules. Horny layer was between groups.
quite pronounced. The cells of the hair follicle regained their shape, but Results: After all procedures, IL10, EGF, VEGF significantly increased
proliferation did not occur in the sebaceous glands. in the skin. The amount of IL20, Filaggrin, Laminin increased after
Conclusion: Thus, a dermatotropic preparation containing vitamins A, E, biorevitalization, but these figures remained the same with the introduc-
and D2, significantly stimulates the reparative activity of the epidermis tion of an extract of the placenta. PDGF decreased in all groups.
after drug atrophy. It is possible that this stimulation does not extend to Conclusion: Hyaluronic acid and placental extract preparation had a
the sebaceous gland stem cell line. positive effect on the skin. The vascularization of the dermis and trophic
skin increased, the basement membrane tightened, the appearance of new
The publication has been prepared with the support of «RUDN cells was stimulated. These drugs have an effect through different mech-
University Program 5-100». anisms. Hyaluronic acid has a moisturizing and structuring effect, the
extract of the placenta enhances skin tropism, stimulates local immunity.

PS-05-010
Histological and inmmunohistolochemical parameters of the skin PS-05-012
under the influence of damaging and stimulating cosmetic Extremely unusual clinical presentation of angiolymphoid hyperpla-
procedures sia with eosinophilia: true neoplasm or reactive process?
Y. Kudrevich1, E. Kuznetsova2, O. Ziganshin3, T. Zayats3, G. Sichugov3 A.C. Lisievici1, T.A. Georgescu2, T. Panazan3, T. Tebeica4
1
Ural State Medical University, Russia, 2 Orenburg State Medical 1
Carol Davila University of Medicine and Pharmacy, Bucharest,
University, Russia, 3 South Ural State Medical University, Russia Romania, 2 Department of Pathology, Bucharest Emergency University
Hospital, Romania, 3 Clinical Emergency Hospital of Plastic Surgery,
Background & Objectives: The article presents the results of the re- Reconstruction and Burns of Bucharest, Romania, 4 Department of
search of the content of collagen types I and III in the skin, the growth Pathology, Dr. Leventer Centre, Bucharest, Romania
factors of FGF2, EGF, VEGF before and after exposure to the skin of an
erbium laser as monotherapy and under complex laser and Background & Objectives: Angiolymphoid hyperplasia with eosino-
biorevitalization. A comparative characteristic of these changes was philia (ALHE) also known as epithelioid hemangioma is a rare and be-
made, conclusions were drawn about the effectiveness of the therapy nign vascular lesion usually located in the head and neck area and ex-
Methods: All patients were divided into two groups of 12 people. The tremely rare on the trunk and extremities. It usually develops in the der-
first group underwent laser treatment of the face. The second group mis, but rarely it can also involve the subcutis.
underwent a biorevitalization procedure. Fragments of skin was taken Methods: We report the case of a 32–year-old male presenting with a
from all patients in 2 months after procedure. In skin samples using tender red nodule near the nail fold on the third finger of the left hand.
immunohistochemical methods with the help of monoclonal mouse anti- First punch biopsy of the lesion was suggestive of a pyogenic granuloma,
bodies, the following parameters were determined: bulk density of type I but the lesion recurred in a very short time and rapidly increased in size.
and III collagen, growth factors FGF2, EGF, VEGF. The decision to surgically remove the lesion through an excisional biopsy
Results: Collagen type III increased in all groups. Collagen type I in- was made, and the specimen was sent to our laboratory for
creased more in the “laser" group compared with “laser + revitalization” histopatological examination.
group. FGF and VEGF increased more in the “laser + revitalization” Results: The excised specimen revealed an ulcerated proliferation of
group compared with the “laser” group. EGF increased more in the "la- blood vessels lined by large and bland endothelial cells, with abundant
ser" group compared with the "laser + biorevitalization" group. cytoplasm and intracytoplasmic vacuoles, in the background of a dense
Conclusion: Based on the data we can be conclud that cosmetic pro- fibrous stroma intermingled with an abundant lymphocytic infiltrate and
cedures stimulate neocollagenogenesis, contribute to the improve- featuring numerous eosinophils. Subjacent bone destruction was noted
ment of skin quality, its density, vascularization of the dermis will and the surgically resection margins were positive. The patient presented
also be intensified, which will lead to increased skin trophism, en- another recurrence within a few months.
hanced metabolic processes, optimization and enhancement of regen- Conclusion: To our knowledge, this is the first case report of bone inva-
erative processes. sive ALHE. Besides its unusual location, this case highlights an extreme-
ly unusual presentation of ALHE, an entity with a long history of disputed
pathogenesis. Between a benign neoplastic process and a reactive vascu-
PS-05-011 lar lesion, we favour the former hypothesis, based on the aggressive
Comparative characteristics of the skin when using hyaluronic acid clinical course of our case.
and placenta extract
Y. Kudrevich1, E. Kuznetsova2, O. Ziganshin3, G. Sichugov3, T. Sayats3
1
Ural State Medical University, Russia, 2 Orenburg State Medical PS-05-013
University, Russia, 3 South Ural State Medical University, Russian P16, P21 and ALK expression in blue nevi family
Federation C. Luca1, O. Stefan1, G. Tudor1, C. Constantinescu1, V. Nica1, L.
Sticlaru1, C. Caruntu2, B. Mastalier1,2, R. Andrei1, S.A. Zurac1,2
1
Background & Objectives: The study involved 40 women, all pa- Colentina Clinical Hospital, Romania, 2 Carol Davila University of
tients were divided into two groups. The first group received a Medicine and Pharmacy, Romania
biorevitalization procedure of the skin, the second group received
injections of an extract of the placenta 5 times with an interval of a Background & Objectives: Blue nevi and related tumours are a hetero-
week. All patients’ piece of skin was taken before the procedure and geneous group of dermal dendritic melanocytes proliferations. They en-
2 months after the procedure. The changes in skin indices was com- compass a spectrum of lesions ranging from benign lesions (common
pared before and after the procedure blue nevus (BN) and cellular blue nevus (CBN)) to malignant blue
Methods: It was used immunohistochemical methods. It was determined melanoma/blue nevus like melanoma (MBM) and including also atypical
the amount of IL8, IL10, IL20, Filaggrin, Laminin, EGF, VEGF, PDGF, CBN (tumour difficult to integrate as benign or malignant, thus remaining
Hyaronidasa with using mono- and polyclonal mouse and rabbit antibod- a challenging diagnosis even for experienced dermatopathologists). We
ies in the skin. These indicators were compared using different drugs to investigated the utility of p16 and P21 immunohistochemical staining in
 Virchows Arch

distinguishing BN/CBN from MBM; we look also for presence of ALK PS-05-015
rearrangements in BN family. Correlating macrophage infiltration with BRAF status and prognos-
Methods: We retrieved 8 BN, 8 CBN and 1 atypical CBN of a total of tic features in melanoma using immunohistochemistry
1154 compound and intradermal melanocytic nevi diagnosed between M. Mc Cabe1, L.F. Tremble 2, R. Werner1, R. Tynan1, P. Forde 2,
2017-2018 in our department; in the same period, we identified 3 C. Heffron1
1
MBM. We performed immunohistochemical tests for p16, p21 and Cork University Hospital, Ireland, 2 University College Cork, Ireland
ALK (as ALK rearrangements surrogate).
Results: 4 of 20 lesions were focally positive for ALK (2 CBN, 1 BN, 1 Background & Objectives: The likelihood of metastasis or recurrence
atypical CBN). P16 staining was positive in all tumours (diffuse in melanoma can be predicted by a number of clinicopathological
positivity: 5 BN, 8 CBN, 1 atypical CBN, 1 MBM; patchy/focal: 3 factors. Macrophages have a wide variety of known tumourigenic
BN and 2 MBM). P21 had mainly patchy/focal expression (3 CBN, 2 properties. This study seeks to determine the profile of the macro-
BN and 2 MBM), diffuse expression being present in 1 CBN and 1 phage infiltrate, whether it is associated with poor prognostic clini-
MBM. copathological factors, and whether there is a correlation between
Conclusion: ALK rearrangement was recently described in Spitz tu- macrophage infiltration and BRAF status.
mours. We identified ALK staining patterns that have not been previously Methods: 43 melanoma cases were retrieved and stained using CD-68,
described in blue nevus tumours. However, its use to distinguish between CD-163, and Arginase. The positive-staining cells were then counted by
benign BN and MBM, as well as the use of p16 and p21 for the same one pathologist and one trainee pathologist and the average of the two
purpose, appears limited. counts was calculated. The pathological reports were then reviewed and
the reported parameters were compared with the degree of macrophage
This work was partially supported by a grant of Romanian-Ministry-of- infiltration in each case.
Research-and-Innovation, CCCDI-UEFISCDI, project number Results: CD-163 stained positive in all cases with a range of 41-662.
61PCCDI⁄2018PN-III-P1-1.2-PCCDI-2017-0341. CD-68 was positive in 22 cases with a range between 0-257. BRAF
was positive in 15 cases. More BRAF+ cases had a positive CD 68
(73.33%) and CD-163 (46.66%) compared with BRAF- cases (39%
PS-05-014 and 42.85% respectively). Higher Breslow tumours appeared to be
The expression of Notch signalling pathway in Merkel cell carcinoma more likely to have a macrophage infiltrate with 33.33% of tumours
M. Matsushita1,2, L. Oka Wardhani1,3, T. Iwasaki4, S. Kuwamoto1, D. with Breslow stage 1-3 positive for CD-163 compared with 56% of
Nonaka5,6, K. Nagata1, M. Kato1, Y. Kitamura2, K. Hayashi1 tumours with Breslow stage 4.
1
Division of Molecular Pathology, Department of Pathology, Tottori Conclusion: Melanoma has a strong CD-163(M2) macrophage infiltrate.
University Faculty of Medicine, Yonago, Japan, 2 Department of A greater number of tumours which stained positively for a macrophage
Pathobiological Science and Technology, School of Health Science, Tottori infiltrate had poor prognostic features which is in keeping with what is
University Faculty of Medicine, Yonago, Japan, 3 Clinical Pathology known about tumour associated macrophages. Increased BRAF mutations
Department, Medical Faculty of Sebelas Maret University, Japan, and immunogenicity could both be a result of the same underlying process.
4
Department of Anatomic Pathology, Graduate School of Medical
Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan, 5 Department of
Cellular Pathology, The Guy's and St Thomas' NHS Foundation Trust, PS-05-016
London, United Kingdom, 6 The Christie Hospital and University of Diagnostic algorithm for spitzoid tumours in children
Manchester, United Kingdom N. Orlinskay1, I. Shlivko1, O. Garanina1, D. Davydeko1
1
FSBEI HE PRMU MOH, Russia
Background & Objectives: Merkel cell carcinoma (MCC) is a rare
and aggressive neuroendocrine skin cancer and approximately 80% Background & Objectives: Spitz nevus (Spitz tumour, juvenile mel-
cases are associated with Merkel cell polyomavirus (MCPyV). Notch anoma, spindle-shaped and epithelioid cell nevus) has a benign nature
signalling pathway regulates cell fate in various tissues including and a good life-prognosis, but may be histologically incorrectly diag-
skin during development and homeostasis. Aberrant activity of nosed as melanoma. Therefore, the purpose of this study was the
Notch signalling relates to various malignancies and it plays a role molecular study of tumour in children with the clinical diagnosis of
as either oncogene or tumour suppressor. We investigated the asso- Nevus Spitz.
ciation of expression of Notch signalling pathway with MCPyV sta- Methods: During the 10-year period, according to clinical indications
tus and prognosis in MCC. and dermatoscopic characteristics, 15 children aged 9 to 12 years old were
Methods: 19 MCPyV-positive and 19 MCPyV-negative MCCs were oper ated on w ith the c linica l d iagnos is of N evus Spitz .
immunohistochemically stained with antibodies for NOTCH1, Immunohistochemical (IHC) staining was performed using antibodies
NOTCH2, NOTCH3, JAG1 and some other downstream factors of to HMB-45, MELA, S100, MITF. FISH studies were conducted using
Notch signalling pathway and analysed. probes targeting 5 loci, including CCND1 at 11q13, MYC at 8q24,
Results: There was no statistically significant association of RREB1 at 6p25, MYB at 6q23, CDKN2A at 9p21, and a CEP 6.
NOTCH1 and NOTCH2 expression with MCPyV-status and progno- Results: Histological examination in 8 cases revealed no histological
sis. NOTCH3 expression was significantly higher in MCPyV- features typical for this tumour: lack of symmetry, uneven arrangement
positive MCC and Kaplan–Meier and multivariate analyses revealed of the “nests” of cells, absence of Camino bodies. All tumours had high
that higher NOTCH3 expression was significantly correlated to better mitotic index of Ki67 - 10% and had atypical mitoses in their structure.
overall survival (p=0.001 and p=0.033, respectively). Higher JAG1 Tumours expressed HMB-45, MELA, S100, MITF, which allowed to
expression was found in MCPyV-negative MCC, but there was no consider these neoplasms as malignant, therefore a FISH study was
significant association between its expression and prognosis. performed.
Expression data of the other downstream in Notch signalling pathway The absence of amplifications of CCND1, MYC, RREB1 and CDKN2A
in MCC will be also shown. and deletion of MYB, which is characteristic of melanomas, has been
Conclusion: In this study, we suggested that NOTCH3 and JAG1 ex- established. Four-year observation of children showed no signs of malig-
pression may be related to tumourigenesis in MCC and NOTCH3 expres- nant growth.
sion, as a tumour suppressor, is an independent predictor of MCC Conclusion: Thus, the histological and IHC characteristics of Spitz-like
outcome. tumours in children are not indicative of malignant melanocytic lesions.
Virchows Arch

PS-05-017 edition of the AJCC TNM staging systems. The impact of the migration
T-cells, Merkel cell polyomavirus and survival in Merkel cell carci- on the prognosis and the sentinel node procedure was examined.
noma: quantity and quality matter. A new simple eye-based Results: Among 141 patients with PCM 64,5%(n=91) patients were
"immunoscore" for pathologists! staged as pT1 category. Stage migration in pT1 category was observed
C. Ricci1, F. Ambrosi2, A. Righi3, L.R. Stefano4, S. Uccella5, M.G. in 26,4%(n=24) of the patients. 14,3%(n=13) of the patients showed an
Papotti6, S. Asioli7 upgrade from pT1a to pT1b. This was due to an new stratification level at
1
Department of Biomedical and Neuromotor Sciences, Bellaria Hospital, 0,8-mm Breslow thickness between pT1a and pT1b category. Another
Bologna, Italy, 2 Pathology Unit, Sant'Orsola-Malpighi Hospital, 12,1%(n=11) of patients underwent a downgrade from pT1b to pT1a.
University of Bologna, Italy, 3 2Department of Pathology, Rizzoli This was a result of the drop out of the mitotic-index in the new classifi-
Institute, Bologna, Italy, 4 Service of Clinical Pathology, Lausanne cation. Within this last group we showed a downgrading of 36,4%(n=4)
University, Switzerland, 5 Unit of Pathology, Department of Medicine nodular melanomas.
and Surgery, University of Insubria, Varese, Italy, 6 Department of The demonstrated migration shows significant impact regarding the per-
Oncology, University of Turin, Italy, 7 Department of Biomedical and formance of sentinel procedure, but there was no difference in the prog-
Neuromotor Sciences, "M. Malpighi" Section of Anatomic Pathology at nosis in both categories.
Bellaria Hospital, University of Bologna, Italy Conclusion: We show a significant migration of PCM within the pT1
category, using TNM 7th versus 8th edition, that had an impact on the
Background & Objectives: In Merkel cell carcinoma (MCC) prognosis sentinel node procedure. There was no significant value concerning the
is influenced by the density, the composition and the topography of dif- prognosis in our study.
ferent lymphocyte subclasses. Herein, we investigated the association
between MCPyV, TILs subtyping (CD3+, CD8+, FoxP3+ and PD-L1),
overall survival (OS) and disease-specific survival (DSS) in a cohort of 95 PS-05-019
MCC patients. Comprehensive evaluation of the mutational spectra detected in pri-
Methods: This study enrolled 95 subjects from three different Italian mary cutaneous melanomas: identification of novel loss-of-function
centers. CD3, CD8 and FoxP3 have been scored as previously reported mutants of TP53
bySihto et al.; the evaluation of PD-L1 on TILs suggested by Lipson et al. I. Ticha1, R. Jaksa1, J. Hojny1, M. Bartu1, K. Nemejcova1, N. Hajkova1,
has been applied. We classified all cases in four “immunoscore” sub- R. Michalkova1, E. Krkavcova1, O. Kodet2, L. Macurek3, P. Dundr1
1
groups, on the basis of TILs and the number of positive immunological Institute of Pathology, First Faculty of Medicine, Charles University and
markers (TILs 0, TILs 1, TILs 2, TILs 3-4). General University Hospital in Prague, Czech Republic, 2 Department of
Results: MCPyV showed statistically significant differences among Dermatology and Venereology, 1st Faculty of Medicine, Charles
immunoscore subgroups. “Dead of disease” and “dead of disease + dead University and General University Hospital in Prague, Czech Republic,
3
of other causes” patients were significantly lower in TILs 3-4 subgroup Cancer Cell Biology, Institute of Molecular Genetics, ASCR, Prague,
compared to the others. OS survival estimated by Kaplan-Meier function Czech Republic
was longer in the TILs 3-4 subgroup starting from 36 months after sur-
gery compared to the others TILs subgroups. For patients with available Background & Objectives: Melanoma is a tumour with worldwide
immunoscore, the only clinical-pathological features significantly associ- increasing incidence. Although the spectrum and frequency of muta-
ated with longer OS at univariate cox regression were MCPyV and TILs tions in melanoma have largely been catalogued, we performed NGS
3-4. analysis of selected genes and an extensive evaluation of detected
Conclusion: MCPyV prompts an immune response involving various variants in a cohort of 115 primary cutaneous melanomas from
lymphocytes subclasses (CD3, CD8, FoxP3 and PD-L1+) in MCC. Czech patients.
CD8+ lymphocytes are the only singly-evaluated lymphocyte subclass Methods: Genomic DNA from 115 FFPE primary cutaneous melanomas
that strongly influenced overall survival and disease-specific survival; (including 46 nodular, 68 superficial spreading, and 1 acral lentiginous
whereas an “immunoscore” model obtained by TILs subtyping (CD3, melanoma; TNM classification pT1=5,pT2=24,pT3=48,and pT4=38)
CD8, FoxP3 and PD-L1) could provide useful prognostic information underwent sequence capture NGS (Illumina) with a custom panel (219
in MCC. kbp; Roche NimbleGen SeqCapEZprotocol). The data was processed by
NextGENe (Softgenetics). The non-synonymous variants with a minimal
average coverage >100x and a frequency ≥10% were comprehensively
PS-05-018 evaluated by in-house biostatistical pipeline. Impact of the TP53 muta-
Comparison of the pT1 primary cutaneous melanomas between the tions was studied by functional assays.
AJCC TNM 7th and 8th edition; a retrospective study in a single Results: A total of 43/54 evaluated genes carried pathogenic or likely
institute pathogenic mutations, most frequently involved in the MAPK signalling
S. Sirimsi1,2, J. Lambert3,2, S. Declercq4, V. Siozopoulou5 pathway (BRAF, NRAS, MAP2K1, KDR), DNA damage response (ATM,
1
Antwerp University Hospital-Department of Pathology, Belgium, BRCA1, BRCA2, KDR, PTEN, TP53) or chromatin remodelling
2
University of Antwerp-Faculty of Medicine and Health Sciences, (ARID1A, ARID2). The most frequent BRAF (63/115;55%), and NRAS
Belgium, 3 Antwerp University Hospital-Department of Dermatology, (36/115;31%) mutations were mutually exclusive, except for one case
Belgium, 4 Middelheim Hospital of Antwerp, Belgium, 5 Department of carrying mutation in both genes outside the hotspot codons. Several nov-
Pathology, Antwerp University Hospital, Belgium el, probably pathogenic mutations were identified using in silico predic-
tion approach (including TP53, HNF1B, MET, PPM1D, CYP19A1), func-
Background & Objectives: The AJCC TNM edition for primary cuta- tional assays confirmed pathogenicity of detected TP53 mutations.
neous melanoma (PCM) was released in 2018 and includes evidence Conclusion: A spectrum of pathogenic mutations, including novel pos-
based changes, especially in pT1 category. The purpose of this study sibly pathogenic mutations across the analysed genes, was described.
was to evaluate the migration in the pT1 category according to the Biostatistical in-house pipeline was validated by functional assays, iden-
AJCC TNM classification and to compare the performance of sentinel tifying new loss-of-function mutations of TP53.
node procedure and the prognostic value.
Methods: Clinical and histopathological data on 141 patients with PCM Supported by Ministry of Health, Czech Republic (Conceptual develop-
in a single Institute, between 2009-2016 were analysed retrospectively. ment of research organization 64165, General University Hospital in
We compared pT1 melanoma classified according to the 7th and 8th Prague, and by project AZV16-30954A).
 Virchows Arch

PS-05-020 development. Loss expression of mismatch repair (MMR) proteins have been
Immunohistochemical expression of E- and N-cadherin in benign found in some cancers such as colorectal, gastric, and ovarian cancers.
melanocytic nevi with halo phenomenon Therefore, we investigated the association of MMR signalling protein expres-
A. Toma1, M. Cioplea2,3, L. Sticlaru2,3, G. Turcu2,4, R.I. Nedelcu2,5, A. sion with MCPyV status and prognosis in MCCs.
Brinzea2,6, L. Peter3, A. Vilaia7, A.I. Savin3 Methods: 20 MCPyV-positive and 20 MCPyV-negative MCC samples
1
Pathology Department, Colentina University Clinical Hospital, from patients were immunohistochemically stained with antibodies to
Romania, 2 Carol Davila University of Medicine and Pharmacy, MLH1, MSH2, MSH6, and PMS2. Each protein expression was evalu-
Bucharest, Romania, 3 Colentina University Hospital, Pathology ated with modified H-score, and the association of expression data with
Department, Bucharest, Romania, 4 Colentina University Hospital, clinicopathological factors were statistically analysed.
Dermatology 1 Department, Bucharest, Romania, 5 National Institute Results: MSH2, MSH6, and PMS2 were expressed higher significantly
for Infectious Diseases Prof. Dr. Matei Balș, Bucharest, Romania, 6 in MCPyV-positive than in MCPyV-negative cases (p=0.026, p=0.005,
Stefan Nicolau Institute of Virology,Bucharest, Romania, 7 Colentina p<0.001, respectively), but there was no difference in MLH1 expression.
Clinical Hospital, Bucharest, Romania In survival analyses, patients with higher MSH6 expression had better
overall survival and disease-specific survival than otherwise by Kaplan-
Background & Objectives: The halo phenomenon refers to the homoge- Meier (p=0.046 and p=0.008, respectively) and univariate (p=0.054, and
nous cell infiltrate surrounding the progressively degenerating nevus cells with p=0.02, respectively) analyses.
spontaneous regression of the melanocytic lesion. Given the scarcity of data Conclusion: The lower expressions of MSH2, MSH6, and PMS2 in
available in the literature regarding the morphological features of melanocytic MCPyV-negative MCCs than in MCPyV-positive MCCs suggest that
nevus cells with halo phenomenon, we sought to characterise the nevus cells impairments of these MMR proteins may play more important roles in
expression of two adhesion molecules, N-cadherin and E-cadherin. tumourigenesis mechanism in MCPyV-negative MCCs, and lower ex-
Methods: An immunohistochemical study has been undertaken of cadherin pression of MSH6 is associated with shorter survival in MCC.
expression in 23 benign melanocytic nevi. All lesions presented with a dense
lymphocytic infiltrate coupled with different grades of melanocytic
involution. Melanocytic immunostaining expression was analysed semi- PS-05-022
quantitatively, assigning one of three grades, grade 3 representing intense Would it be possible for the cases of pathologically diagnosed super-
staining equivalent to that seen in normal structures (epidermis for E- ficial perivascular dermatosis to provide more supportive and infor-
cadherin and nerve tissue or endothelium for N-cadherin). mative pathologic report? Dermatologic and pathologic study
Results: E-cadherin had moderate to intense level of staining in type A C. Yoo1
1
melanocytes, with gradually loss of intensity deeper into the dermis. N- St Vincent Hospital, The Catholic University of Korea, Republic of
cadherin immunostaining was generally weaker than E-cadherin, with Korea
reverse gradient staining in the dermal component of the nevi. E-
cadherin expression in normal keratinocytes and melanocytes was weaker Background & Objectives: Some of skin biopsy specimens are
in areas with dense lymphocytic infiltrate than in non-inflamed area. interpreted pathologically as superficial perivascular dermatosis
Conclusion: E-cadherin/N-cadherin expression in halo phenomenon nevi (SPD). Generally, this description was applied for the cases which
follows the pattern of expression of common nevi (E-cadherin expression showed just mild to moderate perivascular lymphocytic infiltrations
in superficial nests and N-cadherin expression in profound areas) with a even though clinical settings were suggestive of a certain types of
tendency towards intense E-cadherin expression in epithelioid melanocytes. dermatologic conditions. And these pathologic findings were usually
However, presence of inflammatory infiltrate associates with decreasing of understood as nonspecific. This study was aimed to show whether it
E-cadherin expression in both keratinocytes and neoplastic melanocytes. would be possible to make more supportive and informative patho-
logic reports for these SPD cases.
This work was partially supported by a grant of Romanian-Ministry-of- Methods: The pathologic slide re-examination was carried out for the
Research-and-Innovation, CCCDI-UEFISCDI, project number 61PCCDI⁄ SPD cases which were diagnosed in St. Vincent Hospital, the Catholic
2018PN-III-P1-1.2-PCCDI-2017-0341 and CNCS-UEFISCDI, project University of Korea from 2015 to 2018 years, and finally 247 cases were
number no 183/2017PN-III-P4-ID-PCE-2016-0641, within PNCDI-III confirmed. We excluded the cases which showed remarkable epidermal
change, infiltration of eosinophils, neutrophils or plasma cells, pigmen-
tary incontinence, granuloma, remarkable perifollicular inflammatory cell
PS-05-021 infiltration, dermal fibrosis and inflammation in the subcutis. We
Association of mismatch repair proteins with Merkel cell polyomavi- reviewed the medical records of the study cases and dermatologic-
rus status and prognosis in Merkel cell carcinoma pathologic correlations were done.
L.O. Wardhani1,2, M. Matsushita2,3, T. Iwasaki4, S. Kuwamoto2, D. Results: Ages covered wide ranges and sex ratio was approximately
Nonaka5,6, K. Nagata2, M. Kato2, Y. Kitamura3, K. Hayashi2 1:1. Dermatologically, macules, papules, purpura-like lesions or nod-
1
Clinical Pathology Department, Medical Faculty, Sebelas Maret ules were formed in variable sites. Lots of skin diseases were expect-
University, Indonesia, 2 Division of Molecular Pathology, Department ed dermatologically before skin biopsy. Among them, most common-
of Pathology, Tottori University Faculty of Medicine, Yonago, Japan, ly encountered conditions were psoriasis, drug eruption, atopic der-
3
Department of Pathobiological Science and Technology, School of matitis, vasculitis, erythema multiforme and urticaria, and they
Health Science, Tottori University Faculty of Medicine, Yonago, Japan, accounted for about half of them. Afterwards, erythema annulare
4
Department of Anatomic Pathology, Graduate School of Medical Sciences, centrifugum, several spongiotic and psoriasiform dermatitis, lupus
Kyushu University, Fukuoka, Japan, 5 Department of Cellular Pathology, erythematosus and a few tumourous lesions such as Bowen disease
The Guy's and St Thomas' NHS Foundation Trust, London, United were followed.
Kingdom, 6 The Christie Hospital and University of Manchester, Conclusion: Common skin diseases may have histology of SPD in
Manchester, United Kingdom their clinical course. Therefore, if clinical settings were reasonable,
the SPD pattern may not be in conflict with these dermatologic im-
Background & Objectives: Merkel cell carcinoma (MCC) is a rare, aggres- pressions. Tumourous lesions, pigmentary lesions and some acute
sive, neuroendocrine skin cancer and most MCCs are related to Merkel cell dermatopathies could be excluded from SPD. Some rare skin diseases
polyomavirus (MCPyV) infection. Faulty DNA repair induces to mutation or could be thought to have SPD pattern unless particular histology was
aberration in oncogenes or tumour suppressor genes, causing cancer well known.
Virchows Arch

Monday, 9 September 2019, 09:30 - 10:30, Agora 3 Conclusion: Ultrastructural features indicated a variety of functional status of
myocardial telocytes in children: cells with proliferative activity contained
PS-06 | Electron Microscopy
centrioles, others were with synthetical activity contained abundant cisterns
of the granular endoplasmic reticulum; in some telocytes intermediate fila-
ments were found. Telocytes possessed multiple immunohistochemical phe-
PS-06-001
notypes but none were specific only to them.
Primitive or metastatic pleural neoplasia? Transmission electron mi-
croscopy still gives a hand!
F. Fortarezza1, F. Pezzuto1, M. Della Barbera1, G. Pasello2, F. Rea1, F.
PS-06-004
Calabrese1
1 Pathomorphological aspects of degenerative alterations of bone tis-
University of Padua, Italy, 2 Veneto Oncology Institute - IOV, Italy
sue in patients with osteoporosis
Background & Objectives: The amyloidoses are an uncommon group of
T. Pavlova1, I. Bashuk1
diseases characterised by abnormal extracellular deposition of misfolded 1
Belgorod State University, Russia
protein fibrils leading to organ dysfunction. The histopathologic changes
in a renal biopsy from a patient with systemic amyloidosis comprise a
Background & Objectives: More than 250 mln people suffer from os-
spectrum of vascular, glomerular and tubulointestitial amyloid deposition.
teoporosis all over the world. Osteoporosis is considered third in frequen-
Methods: We identified 43 cases of renal amyloidosis after a retrospec-
cy of death after diseases of cardiovascular system and malignant diseases
tive review of all native renal biopsies evaluated in our department from
in people of elder age. Fractures of bones on the background of systemic
2010 through 2019. Demographic information, clinical and laboratory
osteoporosis lead often to persistent disability and increase significantly
data were obtained from electronic records.
the level of mortality.
Results: Among the patients, a male predominance was noted (31 males,
Methods: The bone material was taken in 75 patients, who undergone
12 females). The mean age of the patients at presentation for the entire
arthroplasty of hip joint. After that the Scanning Electron Microscopy on
group was 55 years (range, 26-85). Amyloid was of the AA type in 39
microscope "FE1 Quanta 200 3D" with console for elemental analysis
patients and AL type in 3 patients. The type of amyloid was undetermined
(Na, Mg, Al, S, Fe, C, N, O, P, Ca) was conducted.
in one case. Familial Mediterranean Fever (FMF) was the most common
Results: The decreasing of total square of bone tissue was observed. Bone
primary disease of amyloidosis.
plates of cancellous bone became thinner and perforated, making large
Conclusion: The kidney is one of the most commonly involved organs in
cavities after its partial destruction. The lattice system of trabeculae became
patients with systemic amyloidosis. It is also an important reason of renal
thinner and partially interrupted. Small number of osteons was located
failure. The AA/AL amyloidosis ratio differs between the countries. In
under periosteum. Microfractures of bone balks accompanied with hemor-
our study, this ratio was found to be 13/1.
rhages and presence of blood clots. The osteogenic fiber-cellular tissue was
detected. Osteocyte were altered, their sprouts were short and small.
Conclusion: SEM is reliable and resultative method of study of biolog-
PS-06-003 ical objects in pathology of bone tissue.
Ultrastructural and immunohistochemical phenotype of myocardial
telocytes in children
N. Nizyaeva1, T.V. Sukhacheva2, M.V. Samsonova3, A.L. Cherniaev3, PS-06-005
A.I. Shchegolev1, R.A. Serov4 Changes of nasal mucosa epithelium after CPAP on patients with
1
V.I.Kulakov National Research Center for Obstetrics, Gynaecology and obstructive sleep apnea syndrome
Perinatology of Ministry of Healthcare of the Russian Federation, S. Rjabceva1, V. Кarnialiuk2, L. Makaryna-Kibak2, Y. Yaromenka2, I.
Moscow, Russia, 2 A.N.Bakoulev Scientific Center for Cardiovascular Siamionik1, M. Derevyanko1
Surgery, Moscow, Russia, 3 Pulmonology Scientific Research Institute 1
Institute of Physiology of National Academy of Sciences of Belarus,
under Federal Medical and Biological Agency of Russian Federation, Belarus, 2 Republican Scientific and Practical Centre of
Russia, 4 A.N. Bakulev National Medical Research Center of Otorhinolaryngology, Belarus
Cardiovascular Surgery, Moscow, Russia
Background & Objectives: Obstructive sleep apnea syndrome (OSAS) is
Background & Objectives: Telocytes is a new type of stromal cells of a common condition characterised by repeated episodes of upper airway
mesenchymal origin. Their special morphological features are small size, obstruction during sleep. Continuous positive airway pressure (CPAP) is
the presence of 2-5 long thin processes that surround cardiomyocytes, the “gold” standard of treatment for patients with moderate and severe sleep
intramural vessels, nerve fibers. apnea. The aim of this study was to investigate effect to nasal epithelium in
Methods: The specimens of the right ventricular myocardium of 40 chil- patients with severe OSAS without any nasal pathology after CPAP.
dren with congenital heart disease (tetralogy of Fallot) aged 3–33 months Methods: We evaluated the nasal epithelium before and after CPAP (6
were analysed. We performed electron microscopy and immunohisto- months) in patients (n=10) with severe OSAS by electron microscope (EM).
chemical study with C-kit/CD34/CD44/vimentin/desmin antibody. Results: Before CPAP EM showed destructive-degenerative changes in
Results: In the interstitium of the myocardium the spindle-shaped the ciliated cells: cilia were small (the length of cilia was reduced), de-
(1.8±0.6 μm) and polygonal-shaped telocytes (3.0±1.0 μm) with struction of mitochondria and secretory granules, dilatation of endoplas-
long processes of similar diameter (about 0.1 μm) were identified. mic network with general vacuolization of cytoplasm and reduce the
Telocytes contained cisterns of the granular endoplasmic reticulum, ribosomes number. In few cases (n=3) we found subtotal destruction of
the structures of the Golgi apparatus, mitochondria, intermediate fil- organelles with formed amorphous matter in cytoplasm. The abnormal
aments, centrioles. Lipid drops and myelin-like figures were rare. mucociliary clearance was detected by saccharin test (the average time
The processes of the telocytes were in contact with each other and was 24.91±1.1min). EM of the nasal mucosa after CPAP showed signs of
with stem cells and macrophages. The identification of telocytes was normalization of ciliated cells: cytoplasmic organelles, secretory granules
based on a comprehensive analysis of their shape, size, localization and cilia was correct structure. Clearly visible cilia were surrounded by
and the immunohistochemical phenotype. Telocytes expressed C- amorphous masses. The average time of saccharin test was 17.6±0.8min
kit+,CD34+,CD44+,vimentin+ markers separately and in addition (p<0.05).
they were detected with triple CD34+/vimentin+/desmin- immuno- Conclusion: CPAP could be used to normalize structure of nasal epithe-
fluorescent staining. lium and mucociliary clearance.
 Virchows Arch

Monday, 9 September 2019, 09:30 - 10:30, Agora 3 SPSS Statistics version 20.0 (SPSS Inc., Chicago, IL, USA). The clinical
characteristics and response rate of the patients were compared using Chi
PS-07 | Haematopathology
square tests. Hardy–Weinberg equilibrium Test was estimated by a
goodness-of-fit χ2 test. The Kaplan–Meier method was used to construct
survival curves, and results were compared using a log-rank test. The asso-
PS-07-001 ciation between polymorphism and the risk for DLBCL was calculated by
Polymorphism in pro-inflammatory and immune-related genes in unconditional logistic regression. The survival curves were displayed using
diffuse large B cell lymphoma susceptibility and overall survival in GraphPad Prism 6 software. All significant variables (
Arab descent population: a case -control study Results: In this study, 125 DLBCL patients and 238 ethnically and geo-
S. Al-Khatib1, L. Al-Etan1, N. Abdo1, A. Al-Mistarehi1 graphically matched healthy controls were enrolled. Of the patients,
1
Jordan University of Science and Technology (JUST), Jordan 52.8% were males and 47.2% were females with mean age of 53.7 years
(17 – 89). The mean age for the controls was 43.2 years (6-89) and 38.7%
Background & Objectives: The trends of incidence for NHL are variable were males. Eight single nucleotide polymorphisms (SNPs) in four in-
and show significant age, gender, racial and geographic differences. Generally flammation and immune-related genes (TNF rs1800629G>A,
speaking, the overall incidence of NHL is higher in males than females, rs161525G>A, rs1799964T>C, LTA rs1800683G>A, rs909253C>T,
however, females show more extra-nodal involvement. Regarding geograph- TNFAIP8 rs1042541C>T, LEPR rs1327118C>G, LEP rs2167270G>C)
ic variation, the developing countries show lower incidence but higher grade were genotyped in all subjects (patients and controls). Our study revealed
of B-cell lymphomas in comparison with developed countries. The surround- an increased risk of DLBCL associated with TNF rs1800629G>A in the
ing environment, infectious microorganisms, and life style all play an impor- co-dominant, dominant, and recessive models [odds ratio 2.18, 2.19, and
tant role in NHL pathogenesis. Diffuse large B cell lymphoma (DLBCL) is 2.16, respectively; 95% confidence interval (CI) 1.11-4.31, 1.14-4.22,
the most common NHL. DLBCL is a diverse disease and several studies and 1.10-4.25, respectively; p value=0.047, 0.014; and 0.016, respective-
reveal that different genetic loci are linked with risk or outcome in DLBCL, ly]. As well the risk of DLBCL was increased with LEP rs2167270G>C
among them, the most notably genes are the immunity genes as IL6, IL10, in the recessive model [odds ratio 0.47; 95% confidence interval (CI)
LEPR, CTLA-4, IL4RA, TNF-α and LT-a loci. There is a strong proof that 0.24-0.93; p value= 0.32). Kaplan-Meier analyses of overall survival
changed immunological function imposes an increased risk for lymphoma. revealed that patients with dominant genotype (TT genotype in compar-
Inflammatory and immune response genes are the inventive messengers of ison with combined TC/CC genotypes) of TNF rs1799964 had higher
adaptive immunity, which regulates the immune system function and growth overall survival rate (Log-rank p=0.028).
of lymphoid tissue. The aim of this study is to analyse the relationship be- Conclusion: Our study is the first to address the relationship between
tween 8 single nucleotide polymorphisms (SNPs) in five inflammation and TNF-α-308G>A polymorphism and risk of DLBCL in a Jordanian
immune-related genes (TNF rs1800629G>A, rs161525G>A, Arab population. Our results are consistent with polymorphism
rs1799964T>C, LTA rs1800683G>A, rs909253C>T, TNFAIP8 trends seen in Caucasians rather than Asians in that TNF-α-308A
rs1042541C>T, LEPR rs1327118C>G, LEP rs2167270G>C) and the overall allele was significantly associated with higher risk of DLBCL in
risk and prognosis of DLBCL cases in Jordanian Arab population. Caucasians (OR = 1.21, 95% CI: 1.11–1.32, p < 0.001), but it was
Methods: Study Population (subjects) associated with decreased risk of DLBCL in Asians (OR = 0.70, 95%
The study population composed of 125 patients whom diagnosed with CI: 0.57–0.86, p = 0.001) (based on a meta-analysis by Kan Zhai, Jie
DLBCL at KAUH from the period of 2013 to 2018 and 235 healthy Ding and Yan Zhou). Additionally, our study is the first to show that
cancer-free control subjects with similar geographic and ethnic back- patients with genotype TT of TNF SNP rs 1799964 than those with
ground to patients. All cases of DLBCL has been diagnosed independent- other genotypes after R-CHOP treatment.
ly by a hematopathologist according to the 2008 WHO classification of
tumours of haematopoietic and lymphoid tissues. Funded by Jordan University of Science and Technology Grant #: 2017/
DNA extraction 225.
Genomic DNA was extracted for the DLBCL patients from formalin-fixed
and paraffin-embedded (FFPE) tissue using commercially available kit,
DNeasy Blood & Tissue Kit (Qiagen Ltd., West Sussex, UK), using the PS-07-002
manufacturer’s protocols. Genomic DNA from control-subjects blood sam- Lymphomatoid papulosis type E with subcutaneous tissue infiltra-
ples was extracted using the QIAamp® or Promega DNA Mini Kit according tion and prominent rimming
to the manufacture’s instruction. The quality of extracted DNAwas examined J. Bosch Schips1, O. Servitje2, R. Penín1, M. Panè1, I. Salaverria3, M.
by agarose gel electrophoresis and ethidium bromide staining. The concen- Varela4, C. Muniesa2, F. Climent1
tration and purity of extracted DNAwas assessed by using NanoDrop 1000® 1
Department of Pathology, Bellvitge University Hospital/IDIBELL.
spectrophotometer. The selected polymorphisms were analysed within can- L'Hospitalet de Llobregat, Spain, 2 Department of Dermatology,
didate genes using Sequencing technique (Sequenom® iPLEX assay). Bellvitge University Hospital/IDIBELL, Spain, 3 Department of
RNA extraction and real-time quantitative PCR Pathology, Hospital Clínic/IDIBAPS, Spain, 4 Department of
Total RNA was isolated with TRIzol reagent (Invitrogen, USA) according Pathology, Catalan Institute of Oncology/IDIBELL, Spain
to the manufacturer’s instructions. The reverse transcription was performed
using Transcriptor First Strand cDNA Synthesis Kit (Roche, Indianapolis, Background & Objectives: Lymphomatoid papulosis (LyP) type E is a
IN). Real-time PCR was performed with SYBR Green PCR Master Mix rare variant of LyP. The infiltrates of atypical cells are angiocentric and
(Applied Biosystems, Foster City, CA) on a Bio-Rad CFX96 real-time PCR angiodestructive and may simulate aggressive lymphomas such as
system. The RT-PCR conditions were as follows: sufficient denaturing at extranodal T/NK-cell lymphoma, cutaneous gamma/delta T-cell lympho-
95°C for 50 seconds, denaturing at 94°C for 50 seconds, annealing at 55°C ma and anaplastic large cell lymphoma. We detail the clinicopathological
for 50 seconds, elongation at 72°C for 50 seconds (30 cycles) and a final and molecular features of 5 cases with the goal of identifying a pattern of
cycle at 72°C for 10 minutes. β-actin served as the internal positive control. infiltration previously unreported in the literature.
The RT-PCR products were examined by gel electrophoresis. Methods: The main clinical data was retrieved from the patient’s records.
Statistical analysis Hematoxylin and eosin stained slides and corresponding immunohisto-
All Overall survival (OS) was calculated from the date of diagnosis to the chemistry were analysed and molecular biologic assays were performed.
date of death or last visit for those who were alive at the time of final data Results: Our series is comprised of 3 females and 2 males, with a median
collection and analysis. All statistical analyses were performed using IBM age of 58 years (range: 37-70).
Virchows Arch

All 5 cases had clinical manifestations, presenting as nodules that rapidly between synthesis and degradation of collagen fibers, caused by the down-
evolved into large ulcerations (diameter 1 to 7cm). One patient showed regulation of matrix metalloproteinases (MMPs) and up-regulation of tissue
involvement of tongue as debut manifestation, while the other 4 initially inhibitors of metalloproteinase (TIMP). Nevertheless, the pathogenesis of
developed lesions on the skin. The prognosis was excellent. The patient bone marrow fibrosis in PMF is incompletely elucidated. Our goal was to
with oral disease debut subsequently presented skin involvement. One assess the megakaryocyte expression of MMP-1 and MMP-3, on one hand,
case developed Mycosis fungoides during patient follow-up. and TIMP-1 and TIMP-2, on the other hand, in PMF bone marrow biopsies.
In all cases, morphology showed dermal angiocentric infiltrates of pleomor- Methods: Twenty cases diagnosed with PMF were immunohistochemically
phic cells with hemorrhage, necrosis and ulceration. An epidermotropic studied for MMP-1, MMP-3, TIMP-1 and TIMP-2. MMPs and TIMPs
infiltrate was seen in 2 out of 3 cases with available epidermis. The subcu- expression levels were then correlated with the degree of myelofibrosis,
taneous tissue was affected in the 5 cases and in 3 of them the histological which was graded according to the WHO criteria.
features included rimming of adipocytes by neoplastic lymphocytes. The Results: We identified a significantly increased expression of MMP-3 in
neoplastic cells were positive for CD30 (100%), CD8 (60%), CD4 (40%) megakaryocyte cytoplasm in advanced (grade 2 and 3) myelofibrosis
and TIA1 (60%). EBERs, EMA and ALK1 were negative. Monoclonal compared to prefibrotic/incipient fibrotic cases (p = 0.0138). Moreover,
TCR gene rearrangements were found in 4 cases. Rearrangements of the in cases with overt fibrosis, MMP-3 expression was also observed, with
IRF4/DUSP22 locus on 6p25.3 were absent in all 5 cases analysed by FISH. moderate or intense positivity, in myeloid precursors and bone marrow
Conclusion: We are describing a new pattern of subcutaneous tissue infil- fibroblast. On the contrary, prefibrotic/incipient PMF and advanced PMF
tration previously unreported in LyP type E, with neoplastic cells rimming did not differ significantly from each other with regard to megakaryocyte
hypodermic adipocytes. The identification of rimming should prompt dif- expression of TIMP-1 and TIMP-2, although their levels were higher in
ferential diagnosis with subcutaneous panniculitic-like T-cell lymphoma. plasma within the vascular bone marrow sinuses in cases with overt
myelofibrosis. MMP-1 was almost undetectable in both prefibrotic and
advanced stage of PMF.
PS-07-003 Conclusion: We conclude that MMP-3 megakaryocyte expression is pre-
PAX5 is constitutively expressed in Merkel cell carcinoma and dominantly related to the stage of disease in PMF patients, which in turn
Merkel cell carcinoma cell lines and reveals a broad range of B-cell seems not to influence expression of TIMP-1 and TIMP-2.
characteristic PAX5 splice variants
E. Chteinberg1, W. Gerritsen1, E. Speel1, V. Winnepenninckx1, J. van den
Oord2, A.K. Kurz3, M. Zenke3, A. zur Hausen1 PS-07-005
1
Maastricht University Medical Centre+, The Netherlands, 2 University Detection of gene fusion transcripts in Peripheral T-cell Lymphoma
of Leuven, Belgium, 3 University Hospital RWTH Aachen, Germany using a multiplexed targeted sequencing assay
F. Drieux1, P. Ruminy2, A. Abdel-Sater3, P. Viailly3, V. Marchand3, M.
Background & Objectives: Merkel cell carcinoma (MCC) is a highly Viennot 3 , M. Lanic 2 , V. Fataccioli 4 , A. Dupuy 5, D. Vallois6 , L.
malignant skin cancer of unknown cellular origin. MCC is characterised Veresezan7, J. Picquenot7, C. Bossard8, M. Parrens9, F. Lemonnier5, L.
by a typical trilinear differentiation: epithelial, neuroendocrine, early B- de Leval10, F. Jardin2, P. Gaulard11
1
lymphoid (co-expression of PAX5 and TdT). B-cells and B-cell leuke- U1245 and Pathology Department, Centre Henri Becquerel, Rouen,
mias express characteristic patterns of PAX5 splice variants. We tested the France, 2 Centre Henri Becquerel, France, 3 U1245 Centre Henri
expression of PAX5 on protein and RNA level in MCC and MCC cell Becquerel, Rouen, France, 4 U955 and Pathology Department, Hôpital
lines (MCCcls) including PAX5 splice variants. Henri Mondor, Creteil, France, 5 U955, Hôpital Henri Mondor, Crèteil,
Methods: MCCs (n=16) and MCCcls (MKL-1, MKL-2 and WaGa) were France, 6 Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne,
tested for PAX5 expression by immunohistochemistry (IHC) using dif- Switzerland, 7 Pathology Department, Centre Henri Becquerel, Rouen,
ferent anti-PAX5 antibody clones (DAK-PAX5 (Dako) and SP34 France, 8 Pathology Department, University Hospital, Nantes,
(Roche)). The anti-PAX5 antibody D19F8 (cell signalling) was used for France, 9 Pathology Department, Hôpital Haut-Lèvêque, CHU de
Western-blotting on MCCcls. RT-PCR was performed on RNA isolated Bordeaux, France, 10 Pathology Department, Centre Hospitalier
from fresh frozen MCCs and MCCcls to test for splice variant expression. Universitaire Vaudois (CHUV), Lausanne, Switzerland, 11 U955
Results: Specific nuclear PAX5 expression was detected in all MCCs and and Pathology Department, Hôpital Henri Mondor, Crèteil, France
MCCcls by IHC using DAK-PAX5. In contrast, no expression was found
using the SP34 clone except in one MCC. Western-blotting of the MCCcls Background & Objectives: Peripheral T-cell lymphoma (PTCL) is a
confirmed PAX5 expression by using the anti-PAX5 antibody clone D19F8. heterogenous group of mature T-cell neoplasm, comprising up to 30
In addition, next to full length PAX5 expression, many B-cell characteristic entities according to the revised WHO classification. Over the past years,
PAX5 splice variants (i.e. Δ2, Δ2/3, Δ2/4, Δ9, Δ8, Δ7/8, Δ8/9, Δ6/7/8) high-throughput technologies identified recurrent fusion transcripts of
were identified in MCC tissues and MCCcls on the RNA level. potential therapeutic relevance in PTCL. However, these techniques are
Conclusion: PAX5 IHC using DAK-PAX5 clone is superior to the SP34 difficult to integrate in the clinical routine practice. Here, we report a rapid
clone in MCC and MCCcls, as confirmed by Western-blotting. PAX5 and parsimonious ligation-dependent RT-PCR based assay for the detec-
protein is constitutively expressed in all MCCs and MCCcls. The pattern tion of these gene fusions.
of PAX5 splice variants in MCCs and MCCcls leans strong support to the Methods: 58 probes targeting 32 fusion transcripts were designed and
hypothesis that MCC might originate from early B-cells. applied to RNAs from 256 PTCL biopsies, including 99
angioimmunoblastic T-cell lymphomas (AITL), 15 nodal PTCL with a
TFH phenotype (TFH-PTCL), 43 ALK-negative anaplastic large cell
PS-07-004 lymphomas (ALCL), 14 ALK-positive ALCLs, 7 adult T-cell leukemia/
Bone marrow fibrosis in primary myelofibrosis: the role of MMPs lymphomas (ATLL), 5 primary intestinal T-cell lymphomas (TCL), 3
and TIMPs hepatosplenic TCLs, 1 cutaneous γδ-TCL, 13 NK/TCL, 1 panniculitis-
M. Dincă1, R.-.Z. Bulf1, P. Hărșan1, L. Sticlaru2 like TCL and 52 PTCL not specified (NOS). To identify partner genes,
1
Clinical Hospital Colentina, Romania, 2 Colentina Clinical Hospital, sequencing was performed using a MiSeq system (Illumina).
Romania Results: We detected fusion transcripts in 13/14 ALK-positive ALCLs (7
NPM1-ALK, 3 ATIC-ALK, 2 RNF213-ALK, 1 TPM3-ALK and 1 not
Background & Objectives: The progressive bone marrow fibrosis in prima- found) and 12.4% (30/242) other cases. ICOS-CD28 was detected in 14
ry myelofibrosis (PMF) occurs most likely as a result of an imbalance TFH-derived PTCLs and 2 ATLLs. The other rearrangements were
 Virchows Arch

CTLA4-CD28 (1 TFH-PTCL), ITK-SYK (2 AITLs), ITK-FER (2 AITLs), Pannoramic 250 Flash III scanner. The coordinates of all megakaryocytes
IKZF2-ERBB4 (1 TFH-PTCL, 1 ATLL), TP63-TBL1XR1 (1 ALK- in bone marrow samples were determined and processed with Python
negative ALCL) and 5 VAV1 fusions (2 VAV1-THAP4 and 1 VAV1- programming language (DBSCAN algorithm). We used one-way
STAP2 in 3 PTCL-NOS, VAV1-CD28 and VAV1-MYO1F in 2 AITLs). MANOVA to determine if the differences between groups were statisti-
Conclusion: We describe a multiplex assay for the detection of recurrent cally significant.
fusion transcripts in PTCL. Its simplicity and applicability in the routine Results: The MV of clusters in 1 mm2 in ET=2.3±1.0, in PV=1.4±1.4, in
practice make it an attractive tool to assist pathologists for the character- prefibr-PMF=2.3±1.1, in PMF=1.8±1.1, in HL=0.3±0.2. The MV of
ization of these heterogeneous diseases. megakaryocytes in one cluster in ET=5.9±2.4, in PV=6.5±6.4, in
prefibr-PMF=8.0±4.4, in PMF=8.4±5.6, in HL=3.4±0.4. The largest clus-
ter density was found in ET and prefibr-PMF. Bone marrow biopsies of
PS-07-006 patients with prefibr-PMF and PMF demonstrated clusters with largest
Histiocytic necrotising lymphadenitis number of megakaryocytes. There was a statistically significant differ-
Y. Krivolapov1, I. Spiridonov1, Z. Asaulenko1 ence in histotopographic characteristics of megakaryocytes in Ph-
1
North-Western State Medical University named after I.I. Mechnikov, negative JAK2-mutated CMPNs, F=7.87, p<0.0005; Wilk's Λ=0.443,
Saint-Petersburg, Russia partial η2=0.238.
Conclusion: The histotopographic characteristics of megakaryocytes are
Background & Objectives: Kikuchi-Fujimoto disease (KFD) is a rare, associated with type and stage of CMPN. Obtained results can be used for
benign potentially-hyperimmune disease with a usually good prognosis, developing machine learning for scientific and practical needs.
characterised by fever, lymphadenopathy and potential systemic involve-
ment. KFD pathogenesis is not yet clear, though it is proposed to be a
result of immune response against an unknown infectious agent, which PS-07-008
leads to T-cell and histiocyte activation and apoptosis. In this paper, we Clinicopathologic implication of PD-L1 gene alteration in primary
used Sequential Immunoperoxidase Labeling and Erasing Method adrenal diffuse large B cell lymphoma
(SIMPLE) to elucidate the immunophenotype of the CD123+ cells al- K. Lee1, J.M. Yang2, J. Koh3, Y.K. Jeon3, J.H. Paik2
1
ways present in KFD, that is the purpose of our study. Department of Pathology, Seoul National University Bundang Hospital,
Methods: A total of 5 biopsies of KFD patients were examined. Seoul National University College of Medicine, Seongnam, Republic of
Histological sections of lymph nodes, labelled BCL2, TCL1A, CD3, Korea, 2 Department of Pathology, Seoul National University Bundang
CD20, CD123, CD163, CD68, CD14, MPO, MNDA, PD-L1 through Hospital, Seoul National University College of Medicine, Seongnam,
SIMPLE, were digitized via a Pannoramic 250 Flash III scanner. Republic of Korea, 3 Department of Pathology, Seoul National
Scanned slides were synchronised via the Pannoramic Viewer program. University Hospital, Seoul National University College of Medicine,
Following that, CD123+ cell immunophenotype was analysed. Cell Seoul, Republic of Korea
immunophenotypes were input and analysed in the MS Office Excel
program. Background & Objectives: Primary adrenal diffuse large B cell lym-
Results: 5 subpopulations CD123+ cells were revealed based on the phoma (DLBCL) is a rare subset of DLBCL with uncertain clinicopath-
evaluation of the colocalizations of different antibodies: ologic features. We investigated these features relating with PD-L1 ge-
1. MNDA+CD68+TCL1A+; netic altertaion in adrenal DLBCL.
2. MNDA+CD68+TCL1A-; Methods: Nineteen cases of adrenal DLBCL were analysed with PD-L1
3. MNDA+CD68-TCL1A+; gene alteration including translocation and amplification (PD-
4. MNDA+CD68-TCL1A-; L1:chromosome 9 ratio>4) in comparison with non-adrenal cohort(n=90).
5. MNDA-CD68-TCL1A-. Results: Compared with non-adrenal DLBCL cohort, adrenal DLBCL
Conclusion: We suppose CD123+ cells in lymph nodes with KFD con- was associated high international prognostic index (IPI; score 3-5; adre-
sist of 5 phenotypically different subpopulations, some of them are nal: 68%; non-adrenal: 38%; p=0.021) and poor Eastern Cooperative
plasmacytoid dendritic cells. Further investigations need to determine role Oncology Group performance status (ECOG PS; ≥2; adrenal: 44%;
of the subpopulations in pathogenesis of KFD and other diseases. non-adrenal: 11%; p=0.004). In addition, there was a tendency for high
frequency of presence of B symptom, elevated serum LDH and activated
B-cell-like (ABC) subtype in adrenal DLBCL without statistical signifi-
PS-07-007 cance. Adrenal DLBCL harbored more frequent PD-L1 gene alteration
Histotopographic characteristics of megakaryocytes in Ph-negative (37%, 7/19; translocation: 21%, 4/19; amplification: 16%, 3/19) than
JAK2 mutated chronic myeloproliferative neoplasms non-adrenal DLBCL (6%, 5/86; translocation: 3%, 3/87; amplification:
Y. Krivolapov1, Z. Asaulenko1, I. Spiridonov1, A. Selent'eva1, L. 2%, 2/87; p=0.001). In adrenal cohort(n=19), PD-L1 gene alteration
Polushkina2, A. Lepsky3 was associated with lack of bulky disease (8cm; p=0.047) but
1
North-Western State Medical University named after I.I. Mechnikov, showed tendency for presence of B symptoms, high IPI, elevated
Saint-Petersburg, Russia, 2 Russian Research Institute of Haematology LDH and poor ECOG PS.
and Transfusiology, Saint-Petersburg, Russia, 3 St Petersburg University, Conclusion: Adrenal DLBCL frequently showed PD-L1 gene alteration.
Saint-Petersburg, Russia Adrenal DLBCL may represent a distinct subset of extranodal DLBCL
and PD-L1 gene alteration may contribute to its pathogenesis.
Background & Objectives: The aim of study was to evaluate mean
value (MV) of clusters in 1 mm2 area and MV of megakaryocytes in
one cluster in bone marrow biopsies of patients with Ph-negative chronic PS-07-009
myeloproliferative neoplasms (CMPNs). BCL2 in follicular lymphoma: the overrated guy?
Methods: We examined 95 bone marrow biopsies of patients with JAK2- F. Magnoli1, C. Amaglio1, D. Marchiori1, L.F. Vivian2, V. Martin3, F.
positive CMPNs: 30 patients with essential thrombocythemia (ET), 20 Sessa2, M.G. Tibiletti4, S. Uccella2
1
patients with polycythaemia vera (PV), 25 patients with primary myelo- University of Insubria, Varese, Italy, 2 Unit of Pathology, Department of
fibrosis in prefibrotic stage (prefibr-PMF) and 20 patients with primary Medicine and Surgery, University of Insubria, Varese, Italy, 3 Cantonal
myelofibrosis in fibrotic stage (PMF). 10 patients with Hodgkin's lym- Institute of Pathology, Locarno, Switzerland, 4 Department of Pathology,
phoma were analysed as the control group. The slides were digitized by a ASST Sette Laghi, Varese, Italy
Virchows Arch

Background & Objectives: The translocation (14;18)(q32;q21) is consid- M. Melachroinou1, V. Tzelepi1, P. Patiou1, E. Kourea1, V. Zolota1, A.
ered the genetic hallmark of follicular lymphoma (FL). However, some authors Sarantopoulos 2 , M. Tiniakou 2 , E. Tzouvara 2 , A. Kourakli 2 , E.
have observed a proportion of FL lacking IGH/BCL2 translocation as high as Solomou1, A. Symeonidis1
1
50% in their series, suggesting the existence of geographical differences and University of Patras, School of Medicine, Greece, 2 University Hospital
alternative mechanisms of genetic deregulation in BCL2- cases. of Patras, Greece
The aim of this study was to test the incidence of BCL2- FL in a series of
Italian patients, evaluate its association with clinic-pathological features Background & Objectives: Based on microarray analysis diffuse large B-
and investigate alternative genetic aberrations in this subset. cell lymphoma (DLBCL) can be classified into three subtypes: germinal
Methods: We collected 76 consecutive FLs between 2013 and 2016. All center B-cell-like (GCB), activated B cell-like (ABC), and unclassified.
lymphomas underwent histopathological revision and were GCB subtype tend to have better prognosis than ABC and unclassified.
immunohistochemically characterised. Interphasic fluorescent in situ hy- Several studies have demonstrated that immunohistochemical (IHC) algo-
bridization (FISH) was performed with break apart probes targeting rithms can reproduce the molecular classification. The aim of this study
BCL2, IGH, BCL6 and MYC on paraffin embedded and fresh frozen was to investigate the ability of IHC classification to prognostically stratify
(FF) specimens. Conventional cytogenetic was applied to a subset of cases. DLBCL patients treated with immunochemotherapy. Also, to evaluate the
Results: BCL2 rearrangements and expression were detected in 54% and prognostic significance of MYC, FOXP1, LMO2 and BCL2
87% of cases, respectively (p=0.04), with statistical significance dramat- immunoexpression.
ically increasing when considering intensity of staining (p<0.0001). Methods: A total of 72 cases of DLBCL [40 nodal, 32 extranodal] were
BCL2 expression was related to a lower proliferative index (p=0.02). classified into GCB and non-GCB subtypes by Ηans IHC algorithm [markers:
Among BCL2- cases, 6 showed IGH rearrangement, and were further CD10, BCL6, MUM1] and were examined for MYC, FOXP1, LMO2 and
tested: 1 had a variant BCL2 translocation, 1 had IGH/BCL6 rearrange- BCL2 immunoexpression. Clinical data were available for 50 patients.
ment, the other 4 were negative for both BCL6 and MYC. FISH per- Results: Between GCB [24/72 (33.3%)] and non-CGB group [48/72
formed on FF specimens allowed to detect small positive clones in cases (66.6%)] was not detected a significant difference in overall survival
otherwise categorized as BCL2-. Finally, karyotype reconstruction docu- (OS) and disease-free survival (DFS). In non-GCB group, the overexpres-
mented 3q, 1p and BCL6 abnormalities in 3 cases, respectively. sion of MYC and FOXP1 was associated with shorter DFS (p=0.037),
Conclusion: Our study suggests that t(14;18) is not a constant finding in and with better OS (p=0.048) and longer DFS (p=0.028), respectively. In
FL, its incidence being probably affected by geographical factors. addition, high levels of FOXP1 and low levels of LMO2 (p=0.032) were
correlated with complete response to immunochemotherapy (p=0.032).
In GCB group, MYC overexpression and MYC-BCL6 co-overexpres-
PS-07-010 sion were associated with shorter DFS (p<0.001).
Epstein-Barr virus related bone marrow failure with significant Conclusion: Our results did not confirm the prognostic stratification of
plasmacytosis mimicking multiple myeloma DLBCL based on IHC algorithm. However, they suggest the potential use
L. Marinos1, G. Kanellis1, E. Pouliou1, E. Economaki1, A. Papanikolaou1 of MYC and FOXP1 as predictive and prognostic markers.
1
Haematopathology Department/Evangelismos General Hospital,
Athens, Greece
PS-07-012
Background & Objectives: Epstein-Barr virus (EBV) is commonly related Bone marrow histopathology in accelerated phase of BCR-ABL1
to a wide spectrum of neoplastic, inflammatory or reactive processes with positive chronic myeloid leukemia
variable clinical presentation and histology. One of its relatively rare and un- M. Murari1, S. Sharma1
1
usual manifestations is the induction of bone marrow failure due to extensive SGPGIMS, Lucknow, India
replacement of the hemopoietic lineages by a large number of plasmacytes.
The early diagnosis of this condition is of primal importance since the severe Background & Objectives: Chronic Myeloid Leukemia is a triphasic mye-
bone marrow failure can have a potential fatal outcome for the patient. loproliferative neoplasm. Currently, the accelerated phase is defined by clin-
The objective of this study is to alert pathologists on this situation through ical and laboratory criteria including leucocyte and platelet counts, basophilia
the presentation of the bone marrow histological findings of two patients. and blasts. Marrow trephine biopsy in not routinely carried out in CML and
Methods: A man and a woman aged 61 and 71 years-old respectively the histopathological features of accelerated phase are not well characterised.
were admitted for sudden onset of fever and pancytopenia. A bone mar- Methods: This study presents bone marrow trephine biopsy findings in
row biopsy was performed the findings of which are described . 40 patients of BCR-ABL positive CML in accelerated phase. Marrow
The diagnostic approach included morphologic study of hematoxylin and trephine biopsy cores were fixed in B5, decalcified, paraffin-embedded
eosin (H&E) stained slides, immunohistochemistry and in situ hybridiza- and stained with H&E, Reticulin and VG / Masson Trichrome stains,
tion (ISH) for the detection of small RNA transcripts of EBV. study of histomorphology and topographic distribution of hematopoietic
Results: Histology of the bone marrow disclosed an extensive and stromal elements was done.
plasmacytic infiltration (80% and 90% of the total cells respectively) with Results: Marrow biopsy showed hypercellularity, predominantly mye-
very few remaining cells of the hemopoietic lineages. loid hyperplasia (90%) and megakaryocytic hyperplasia (85%) with
Immunohistochemistry revealed polyclonality of the plasmacytes, while prominent clustering and dysplasia (65%). Blasts ranged 5-18%, intersti-
ISH detected the presence of EBV. tially dispersed in most, with random / paratrabecular clusters in 10% of
Conclusion: Bone marrow failure through EBV-induced plasmacytosis is cases. Fibroblastic proliferation with sinusoidal hematopoiesis was seen
a rare and potentially lethal manifestation of EBV infection.Its early di- in 25% cases. Increased reticulin (grade I-II) was seen in most of the
agnosis with bone marrow biopsy is of paramount importance and re- cases, 36.4 % had grade III fibrosis. Erythropoiesis was uniformly re-
quires implementation of immunohistochemistry as well as ISH for the duced. Five cases showed prominent myelofibrotic changes and reduc-
detection of the virus tion in hematopoietic elements.
Conclusion: Marrow histopathology in accelerated phase of CML is
quite variable. Megakaryocytic dysplasia, blasts and marrow fibrosis
PS-07-011 were better evaluated in biopsy compared to marrow aspirates, however,
Expression of MYC, FOXP1, LMO2 and BCL2 in diffuse large B- basophilia was not well appreciated in the biopsy. The prognostic rele-
cell lymphoma classified into GCB and non-GCB subtypes by immu- vance of marrow histopathology and its correlation with peripheral blood
nohistochemistry. Correlation with clinical parameters findings would necessitate sequential observations on trephine biopsy.
 Virchows Arch

PS-07-015 treated with imatinib: all achieved complete hematologic remission ex-
Peculiarities of megakaryocytes and platelets variation in the cept the FGFR1-rearranged patient.
microelementosis condition The other FGFR1-rearranged patient (MPN+T-LBL) was treated with
Y. Lyndina1, V. Sikora2, N. Gyryavenko3, M. Lyndin4, L. Karpenko2, A. polychemotherapy and allogeneic transplantation followed by relapse.
Romaniuk1 Conclusion: Our cases confirm responsiveness of PDGFRA/B-
1
Sumy State University, Ukraine, 2 Sumy State University, Medical rearranged MLNs to imatinib and possible existence of not yet known
Institute, Pathology Department, Ukraine, 3 Sumy State University, fusion TKs, which may benefit from TKIs. Identification of LBL in
Department of Pathology, Ukraine, 4 Sumy State University, Medical MLNs avoids overtreatment/nonresponse to intensive chemotherapy rec-
Institute, Department of Pathology, Ukraine ommended in LBL.
FGFR1-rearranged MLNs exhibit poor prognosis without an effective
Background & Objectives: The aim of our study was to characterise targeted treatment. Recently, pemigatinib, a selective, potent inhibitor of
megakaryocytes and platelets variation under the influence of heavy metal FGFR1, has shown promising results.
salts and determine the peculiarities of these changes in recovery period.
Methods: The laboratory rats (n=48) were used for the conduction of
experimental investigation. They were divided into two groups: control – PS-07-017
animals which drank clean water and experimental – rats which drank water Next-generation sequencing-based clonality assessment of immuno-
with heavy metal salts (Zn, Cu, Fe, Mn, Cr and Pb). The bone marrow globulin gene rearrangements distinguishes relapse from second pri-
structure and blood parameters were studied on 30, 90, 120 and 180 day. mary classical Hodgkin lymphoma
Results: During 90 days of intoxication the amount of megakaryocytes D. van Bladel1, M. van den Brand1, J. Rijntjes1, A. Brinkman1, T. Reigl2,
increased on 40%(р=0.017). There were changes of shape, size (small N. Darzentas3, C. Hess1, K. Hebeda1, P. Groenen1, H. van Krieken1, B.
and giant), nuclear-cytoplasmic ratio, polysegmentation of nuclei and loss Scheijen1
1
of megakaryocyte-sinusoid contacts. It was found the platelets increase Radboudumc, The Netherlands, 2 CEITEC-Masaryk University,
by 11% in the blood. Suspending the addition of pollutants to the animal's Czech Republic, 3 University Hospital Schleswig-Holstein, Germany
diet was accompanied by progressive restoration of bone marrow-blood
parameters. Simultaneously with disappearance of megakaryocytes mor- Background & Objectives: Classical Hodgkin lymphoma (cHL) is highly
phological variations the area of thrombocytopoiesis was decreased by curable, however relapse still occurs in up to 30% of (advanced) cHL cases.
28%, the thrombocytes – by 5.3%. Case reports and small series have shown that some of these relapses appear
Conclusion: The intake of heavy metal salts in elevated concentrations to be a new primary cHL. Conventional clonality assays for cHL has thus far
provokes significant disorders in thrombocytopoiesis which leads for been hampered by low frequencies of Hodgkin and Reed-Sternberg cells
platelets increase in the blood. Although there was a significant improve- and limited DNA quality obtained from formalin-fixed paraffin-embedded
ment bone marrow-blood characteristics during recovery period, their tissues. Within the EuroClonality-NGS Working Group, we developed a
values do not reach the indicators of the intact group animals. novel approach to detect immunoglobulin heavy chain (IGH) and k light
chain (IGK) gene rearrangements. The objective of our study is to determine
the clonal relationship between diagnosis and recurrent cHL to assess the
PS-07-016 incidence of second primary malignancies.
Myeloid/lymphoid neoplasms with eosinophilia and gene rearrange- Methods: We collected 70 paired diagnosis-recurrence cHL cases includ-
ment: a report of 7 cases ing early and late recurrences. Gene-specific IGH-VJ-FR3, IGHDJ, IGK-
C. Rossi1, D. Fanni1, G. Martino2, G. Faa1,3, S. Ascani4 VJ and Intron-Kde primer sets were used to perform next-generation
1
Division of Pathology, Department of Medical Science, University sequencing (NGS)-based clonality analysis with Ion Torrent PGM.
Hospital San Giovanni di Dio, AOU Cagliari, University of Cagliari, Bioinformatics analysis is performed with the interactive web-based
Italy, 2 Institute of Haematology and Centre of Haemato-Oncology immunoprofiler ARResT/Interrogate.
Reserch (CREO), University and Hospital of Perugia, Italy, 3 Temple Results: Preliminary results of 7 paired diagnosis-relapse samples dem-
University, Philadelphia, Pennsylvania, USA, 4 Pathologic Anatomy, onstrates the presence of identical clonotypes in 2 cases, while distinct
Santa Maria Hospital, University of Perugia, Terni, Italy clonotypes were observed in 3 other cases suggesting a second primary
lymphoma. No specific clonotype were identified in either diagnosis and/
Background & Objectives: Myeloid/lymphoid neoplasms (MLNs) with or relapse of the remaining 2 samples. Additional cases of recurrent cHL
eosinophilia and gene rearrangement are rare diseases characterised by have to be analysed to reveal the true incidence of clonally unrelated
myeloid and/or lymphoid proliferation, eosinophilia, and a fusion gene lymphomas in recurrent cHL.
with constitutive tyrosine kinase (TK) activity. These disorders are re- Conclusion: This study is an important step towards establishment of
sponsive to TK inhibitors (TKIs) excluding FGFR1-rearranged MLNs, NGS-based clonality assessment in clinical practice for cHL, and even-
for which there is currently no standardised therapy. tually the improvement of therapeutic management of recurrent cHL.
The aim of this study is to report 7 cases of MLNs collected from 2003 to
2018. Supported by Grant: KWF 11137.
Methods: All patients underwent bone marrow (BM) core biopsy that
showed hypercellular BM, hyperplasia of eosinophilic granulopoiesis
and features of myeloproliferative neoplasms (MPNs). In 4 out of 7 PS-07-018
patients with lymphadenopathy, excisional lymph node biopsy was Follicular lymphoma and in situ mantle cell neoplasm: a rare com-
performed revealing a T-lymphoblastic lymphoma (T-LBL). Gene bination with peculiar genetic and clinical features
rearrangement was assessed with cytogenetic and/or molecular L.F. Vivian1, F. Magnoli1,2, F. Sessa1, M.G. Tibiletti2, S. Uccella1
1
analysis. Unit of Pathology, Department of Medicine and Surgery, University of
Results: In 6 out of 7 cases, the fusion gene has been identified: FIP1L1- Insubria, Varese, Italy, 2 Department of Pathology, ASST Sette Laghi,
PDGFRA (2/7), ETV6-PDGFRB (2/7) and ZMYM2-FGFR1 (2/7). In Varese, Italy
one case, no currently known TK fusion genes were recognized.
Two PDGFRA-rearranged patients (one with MPN+T-LBL), two Background & Objectives: Composite lymphomas are rare entities in
PDGFRB-rearranged patients, one FGFR1-rearranged patient (MPN+T- which two or more different lymphomas coexist in the same site. Little is
LBL) and the one with unidentified rearrangement (MPN+T-LBL) were known about their clinical and prognostic implications. We present a
Virchows Arch

unique case of combination between a low-grade follicular lymphoma PS-08-002

(FL) and an in situ mantle cell neoplasm (ISMCN), focusing on its mor- Pulmonary amoebic abscess - resolved with application of
phological, immunophenotypical, genetic and clinical features. metagenomics (universal pathogen detection)
Methods: We evaluated a 75-year-old female patient who first presented K. Kashofer1, A. Thueringer2, L. Brcic1, G. Gorkiewicz1
1
in 2012 with a cervical lymphadenopathy. Every newfound lesion was Institute of Pathology, Medical University of Graz, Austria,
2
biopsied in the 6-year follow-up, until exitus. Tissue samples were rou- Medical University of Graz, Austria
tinely processed for morphological, immunohistochemical and cytoge-
netic evaluations. FISH analysis was performed using three different ap- Background & Objectives: Pulmonary amebic abscesses are often hard
proaches: break-apart probes (BCL2, BCL6, CCND1); dual-color dual- to diagnose since microorganisms cannot be readily captured in the back-
fusion probe (IGH/BCL2); spectral karyotyping (SKY) FISH. ground of a severely inflamed tissue.
Results: In the first lymph node biopsy, a coexistence of FL grade 1-2 and Methods: Shotgun metagenomics was applied to extracted DNA from a
ISMCN was diagnosed. Bone marrow trephine showed infiltration by FL and lung abscess and resolved with next-generation sequencing. Human se-
no signs of MCL. Two and four years later, respectively, a new cervical lymph quences were bioinformatically removed and the remaining non-human
node and a cutaneous lesion were sampled, showing FL localization without sequences identified by database queries. The bioinformatics pipeline
ISMCN or MCL. In 2018, the patient died of disease. In the first lymph node used in our approach encompasses the PathSeq toolkit for metagenomics
sample, SKY FISH revealed three clones including one diploid (46XX) and based pathogen detection (Kostic AD, Nature Biotech 2011).
two abnormal ones (46,XX,t(11;14)(q13;q34),del(11)(q11q22)[13]/ Results: We report on a 58 year old female who presented with an abscess
49,XXX,t(2,18)(p11;q21),+4, del(5)(q?),der(17)t(1;17)(q22-25; q25),+ involving the lung and extending into the liver. Histology of the resected
der(18)t(2;18)(p11;q21)[23]). FISH analysis confirmed the involvement of lung tissue showed a liquefactive necrosis but without identifiable micro-
BCL2, BCL6 and CCND1 rearrangements respectively in 71%, 86% and organisms including amebal structures. However, serology was highly
11.5% of nuclei. positive for Entamoeba histolytica (IHA, IgG ELISA) in this patient.
Conclusion: The progression of the FL influenced the adverse outcome Curiously, PCR for E. dispar and E. histolytica performed on DNA ex-
of the patient, whereas the ISMCN never progressed to an overt MCL. tracted from lung tissue was negative. Shotgun metagenomics performed
Accordingly, the ISMCN component had a simpler karyotype than the FL on the tissue was able to detect Entamoeba histolytica DNA in low con-
component. A careful cytogenetic analysis of composite lymphomas may centration (2 reads out of 3.47 Mio. reads) verifying the amebic origin of
provide significant prognostic information. the pulmonary abscess.
Conclusion: This case highlights the power of metagenomics to resolve
uncommon (infectious) diseases. This method represents a "universal
Monday, 9 September 2019, 09:30 - 10:30, Agora 3 pathogen detection" approach principally able to detect each possible
PS-08 | Infectious Diseases Pathology microorganism in human tissue. Interestingly, targeted PCR failed in
our case which indicates that in certain instances shotgun metagenomics
seems to be more sensitive and represents therefore a superior detection
PS-08-001 method.
Hydatid disease: report of four cases localized to bone
Z.B. Erdem1, O. Yalcin1, S. Yildirim2
1
Okmeydani Training and Research Hospital, Istanbul, Turkey, 2 Maltepe PS-08-003
University Medical School, Istanbul, Turkey Study of paediatric empyema thoracis treated by surgical
decortication
Background & Objectives: Hydatid disease is an infectious disease M. Khawale1, S. Singaravel1
1
caused by Echinococcus species. Echinococcus granulosus is the most Department of Pathology, Bai Jerbai Wadia Children's Hospital,
common cause of hydatid disease. Hydatid cysts are mostly seen in liver India
and lung. Rarely spleen, kidney, central nervous system, cardiac muscle,
bones and subcutis can be involved Background & Objectives: Paediatric empyema thoracis (PET) is a
Methods: We performed a retrospective analysis of pathology reports complication of bacterial pneumonia resulting in increased morbidity,
between the years 2009 and 2019. Four patients had cyst hydatid lesion primarily attributable to poverty, overcrowding and poor compliance to
located in bone. conservative therapy. Surgical decortication is a last resort, performed in
Results: Patients ages ranged from 27 to 64 years; 3 of them were females neglected cases.
and 1 of them was a male. Lesions were located in acetabulum, proximal Methods: We conducted a study of PET treated by surgical decortication
of tibia, lumbar 2 vertebrae and mandible. Radiologically only one of of two years duration at our urban tertiary care paediatric hospital in
them had a differential diagnosis of hydatid cyst. Others had osteosarco- western India. We studied demographic features, clinical presentation,
ma, giant cell tumour of bone and enchondroma as differential diagnosis radiological details, laboratory data, microbiological findings and histo-
radiologically. Grossly all specimens consisted of fragmented bones pathology of pleural peels in these patients.
intermixed with white membranous pieces. Microscopic evaluation re- Results: Eighty six cases of PET were identified. The age range was 2
vealed that the white membranous pieces consisted of laminated and months to 11 years and 58% of patients belonged to the 1-5 years age
germinal membranes of the cyst hydatid wall. Some pieces showed thick group. The Male:Female ratio was 1.2:1. Almost all the patients presented
fibrous capsule surrounding the cyst wall. with fever, cough and dyspnea. Radiology was available in 55 cases and
Conclusion: Hydatid cysts are slow growing lesions which are usually the most common finding was loculated pleural effusion. Pleural fluid
asymptomatic during this period. Nonruptured cysts cause symptoms by was examined in 25 cases and showed a total count ranging from 600-
compressing to the adjacent structures. When ruptured, cysts can cause 20,000 cells/cu mm with predominance of neutrophils. CRP was elevated
severe inflammatory and allergic reactions. Differential diagnosis of liver in all cases. Microbiological findings were available in 55 cases and 18
and lung lesions of hydatid disease is easier when compared to bone cases were culture positive. The most commonly cultured organisms were
lesions. Bone involvement by hydatid disease doesn't have a characteris- Klebsiella pneumoniae and Methicillin-resistant Staphylococcus aureus.
tic appearence radiologically which makes it hard to distinguish from Histopathology showed suppurative inflammation (13 cases), granulation
malignancies and other benign cystic lesions. Bone hydatid disease is a tissue (5 cases), fibrosis (11 cases), mixed pattern (50 cases), round cell
rare entity (%3 of all cases) and must be kept in mind when evaluating a tumour (1 case), necrotizing granulomatous inflammation (6 cases - 3
cystic lesion of bone. were positive for Mycobacterium tuberculosis on Gene Expert).
 Virchows Arch

Conclusion: Early diagnosis and effective management of pneumonia caseous necrosis located in the lungs, liver, kidney and heart. Cirrhosis
would lower the morbidity in such cases. was also noted. Biochemistry tests confirmed tuberculosis.
Conclusion: Myocarditis is usually caused by a viral infection, but bac-
teria, fungi and parasites have also been documented. In our cases, we
PS-08-004 illustrated a complicated and lethal infection with a common Influenza
Co-infection of the human placenta and problem of the mother-to- virus, a highly disseminated tuberculosis with myocardial involvement,
child transmission of HIV and an atypical fungal myocarditis in a young female.
A. Kolobov1 The cardiac muscle requires rigorously examination during autopsy be-
1
Saint Petersburg University, Russia cause it can clarify the final report regarding the cause of death. Ancillary
tests are mandatory to sustain the infectious etiology.
Background & Objectives: The immune parameters of the placenta of the
HIV-infected woman during pregnancy have been linked to the mother-to-
child transmission (MTCT) of HIV. The purpose of this study was to inves- PS-08-006
tigate the characteristics of the placentas and the expression of the CD14+ The role of intraoperative frozen section in the joint arthroplasty:
receptors in macrophages of the placentas of Russian HIV-infected women retrospective review with CD66b staining
and to compare it with the expression of the immune receptors in placentas Y. Yoo1, S. Park1, S.H. Sung1, H.P. Shin2
1
of women with co-infections and healthy women as controls. Department of Pathology, Ewha Womans University College of Medicine,
Methods: The placentas were collected from three groups of patients: Seoul, Korea, Republic of Korea, 2 Department of Internal Medicine, Kyung
Group A – cases with children infected with HIV (11 placentas), Group B Hee University Hospital at Gangdong, Republic of Korea
– cases with non-infected children born to HIV-infected mother (11 pla-
centas) and Group C – placentas from women without any infection (16 Background & Objectives: The preoperative diagnosis of infection
placentas). In morphological analysis routine staining (hematoxylin and eo- in joint arthroplasty is important for clinical management. For deci-
sin) and microscope investigation were used. HIV-infection and the DNA- sion making for joint infection, surgeons depend on intraoperative
viruses of family Herpesviridae was confirmed immunohistochemically. frozen section diagnosis. However, the evaluation of polymorpho-
CD14+ receptors expression was studied immunohistochemically. nuclear leukocytes (PMNs) in frozen section is sometimes difficult.
Results: Placental infection was detected in 91% of placentas Group A, We compared the intraoperative performances of the frozen section
64% of Group B. In Group A the placental inflammation (73%) repre- diagnosis to evaluate the utility of intraoperative frozen section and
sented combined bacterial and viral changes, and 18% had isolated viral performed the immunohistochemical stain for PMNs (CD66b) for
inflammatory changes – HIV and DNA-virus. In Group B the majority of confirmation.
placentas had HIV changes (55%). Expression of CD14+ in cytoplasm of Methods: This study includes 74 patients with indicated surgery after
chorion villi cells and endotheliocytes was the highest in Group A (14.14 arthroplasty of knee, hip, shoulder, and ankle. The presence of PMNs
±1.11%), followed by Group B (10.04±1.37%), when compared with was determined on frozen sections intraoperatively and permanent sec-
control Group C (3.21±0.43%, р<0.05). tions, respectively. A histologic section, frozen or permanent, was con-
Conclusion: In our study there was a significant prevalence of bacterial sidered positive for infection if there were more than 10 PMNs per HPF,
and combined bacterial and viral inflammatory changes in the placentas excluding surface fibrin and inflammatory exudate, in at least five sepa-
with MTCT of HIV compared to the placentas of the women without rate microscopic fields. In equivocal cases, the immunohistochemical
MTCT. The presence of viral infections (HSV and CMV) and HIV was stain (CD66b) was performed to identify PMNs.
accompanied by the significant increase of CD14+ macrophages in the Results: The ratio of male and female patients was 29:45. The mean age
placentas at time of delivery. was 68.4 years. Postoperatively, 31 patients were diagnosed with infec-
tion (31/74, 42%). Of 31 patients with infection, sensitivity and specific-
ity of frozen section were 97% (30/31) and 95% (40/42), respectively. Of
PS-08-005 42 patients without infection, two cases showed false positive results in
Severe infectious myocarditis with three distinctive microorganisms intraoperative frozen section diagnoses (2/42, 5%).
O. Neagu1, L. Luca2, A. Tita2, M. Bosa2, D.I. Enea1, M.C. Ceausu1,3 Conclusion: The frozen section revealed a significantly higher perfor-
1
University Emergency Hospital Bucharest, Romania, 2 "Mina mance and concordance with the permanent histology. Therefore, the
Minovici" National Institute of Legal Medicine, Bucharest, frozen section diagnosis is reasonably applicable to diagnostic work-up.
Romania, 3 "Victor Babes" National Institute of Pathology, Romania

Background & Objectives: Myocarditis is an uncommon and puzzling PS-08-007

diagnosis to establish in vivo. Depending on its stage and activity, the Clinical and morphological features of five cases of caseous BCGitis
presentation includes acute heart failure, tachyarrhythmia or sudden A. Sapargaliyeva1, A. Pak1, B. Alibekov1
1
death. Generally, the severe cases are confirmed during histopathological Pathology Bureau of the City of Almaty, Kazakhstan
examination of the autopsy specimen.
Methods: We report three cases of myocarditis confirmed post-mortem, Background & Objectives: BCGitis are among the most frequent com-
caused by peculiar infectious agents. plications of BCG vaccination. In accordance with the existing classifi-
Results: A 66-year-old woman died in the hospital with signs of cation, there are simple and purulent BCGitis, and the latter ones are
meningo-encephalitis two days after admission. The tissue samples dem- included in the group of severe complications requiring surgical treat-
onstrated a mild encephalitis, interstitial pneumonia and myocarditis with ment. We would like to discuss the morphological features of cases of
lymphocytes, plasma cells and macrophages. An infection with Influenza caseous BCGitis without suppuration in five children.
virus was detected in her airways fluid. Objectives: We conducted a morphological analysis of caseous BCGitis.
Another bizarre case is a 19-year-old girl who was found dead, lacking Methods: We conducted a morphological study of axillary lymph nodes
any pathological history or trauma injuries. The heart fragment showed of five children after axillary node dissection on the left. The age of
acute purulent myocarditis. A PAS stain identified hyphae and spores in patients varied from five months to twenty-two months during the initial
the myocardial abscesses. examination (there were three boys and two girls). The material for anal-
The third case is a 40-year-old man, with unknown identity, discovered ysis was provided by the National Center of Tuberculosis, where children
lifeless on a street. He had innumerable whitish, confluent nodules, with were treated in the surgery department.
Virchows Arch

Results: Results: in all cases, caseous lymphadenitis was diagnosed. Massive Results: We present a case of an IP in an 8 year old boy, which developed
focuses of caseous necrosis were surrounded by granulation tissue of varying in the chest wall several weeks after a minor trauma. Clinically sarcoma
degrees of maturity, which included round-cell cells and giant cells. In the was suspected but histology specified the lesion as IP with a granulation
lymph nodes of children (age group from 18 months to 22 months) in the foci tissue like appearance and abundant histiocytes in the tissue. 16S rRNA
of caseous necrosis, we identified massive deposits of calcium. In addition, gene sequencing identified three bacteria in high concentration in the
two types of giant cells (foreign-body giant cells and Langhans giant cells) resected tissue, namely Fusobacterium nucleatum, Aggregatibacterium
revealed signs of cell injury with intracellular fatty change and calcium accu- actinomycetemcomitans and Campylobacter rectus, the latter not cap-
mulation. Lymph nodes had the appearance of conglomerates consisting of tured with microbiological culture.
multiple small and large tuberculous foci. There were numerous epithelioid Conclusion: Our case sheds new light on the pathogenesis of IP. All
cell granulomas outside of the lymph nodes. three (opportunistic) pathogens belong to the oral microbiota and are
Conclusion: Caseous BCGitis is characterised by foci of caseous necrotic frequently found in the interdental plaque. Retrospectively it turned
lesions within affected axillary lymph nodes, total destruction of lymph out that the patient had a bad dental status. Supposedly, the preceding
nodes’ architecture and a high risk of dissemination of BCG infection. minor trauma led to tissue alterations (e.g. hematoma) which might
have enabled endogenous (oral) opportunists to colonize this site
which in turn lead to chronic inflammation and ultimately IP.
PS-08-008 Indeed, infection, trauma, and foreign bodies are among the numer-
Clinical and morphological study of ten cases of pulmonary ous reported etiologies that may be involved in the pathogenesis of
echinococcosis IP. Noteworthy, molecular pathogen detection performed in our case
A. Sapargaliyeva1, A. Duysenova2, A. Pak1 additionally detected the microaerophilic C. rectus in the lesion,
1
Pathology Bureau of the City of Almaty, Kazakhstan, 2 Department of which was missed in clinical microbiology with possible therapeutic
Infectious Diseases, Kazakh National Medical University, implications.
Kazakhstan

Background & Objectives: Cystic echinococcosis is common in PS-08-010

Kazakhstan and its diagnosis is a clinical problem. Cystic echinococcosis Pulmonary nocardiosis diagnosed by culture-independent,
often involves lungs in the pathological process. As a rule, echinococcal panbacterial (16S rRNA gene) sequencing - a series of 3 cases
cysts in the lungs are detected by chance as well-defined nodules, which M. Zacharias1, L. Brcic1, K. Kashofer1, G. Gorkiewicz1
1
often lead to the erroneous diagnosis of "tuberculoma" and prescription of Institute of Pathology, Medical University of Graz, Austria
anti-tuberculosis drugs.
Objective: A retrospective analysis of ten cases of pulmonary echinococ- Background & Objectives: Pulmonary nocardiosis (PN) is an infre-
cosis. In all cases, patients were treated from tuberculosis. quent but severe infection due to Nocardia spp. often associated with
Methods: All patients, including seven females and three males, were underlying diseases like COPD, HIV infection or cancer. The lung
admitted by the Republican Center of Tuberculosis of the Republic of normally represents the primary site of infection with Nocardia.
Kazakhstan with a diagnosis of pulmonary tuberculoma over the period Besides chronic courses PN can disseminate (brain, skin) and even-
of three years (from 2013 to 3015). All patients received anti-tuberculosis tually lead to death of patients. Nevertheless, diagnosis of PN is
drugs and due to the lack of effect of the therapy, they went through difficult since radiological findings are not specific and classical mi-
surgical treatment, including segmentectomy (nine cases) and lobectomy crobiological methods often fall short.
(one case). The age of patients varied among males from 7 years to 16 Methods: Culture-independent, panbacterial (16S rRNA gene) sequenc-
years, among females from 23 years to 34 years. Five patients had close ing resolved with next generation sequencing was performed on resected
contact with a relative with active TB. All patients lived in rural areas. tissue because of suspicious lung nodules.
Results: Morphological examination detected cystic echinococcosis in all Results: Three cases of PN were diagnosed by molecular means which
cases. Hydatid cysts in lungs had typical structure and cysts’ diameters were suspicious of pulmonary neoplasia. Captured sequences of Nocardia
were less than 3 cm. The definitive diagnosis of echinococcal cyst in the were most homologous to N. asiatica/abscessus, N. cyriacigeorgica, as
lung was based on the histological examination of resected lung tissue well as N. pneumoniae, all species described in PN. Histological repre-
after the surgery. sentation of lung lesions was not specific and showed diverse histology
Conclusion: Morphological diagnosis of pulmonary echinococcosis does including chronic and acute inflammation.
not represent a problem. For general practitioners, diagnostic difficulties Conclusion: Diagnosis of nocardiosis is difficult since clinical appear-
are associated with echinococcal cysts smaller than 3 cm in diameter, ance is not specific and microbiological examination often fails in detec-
which, in the absence of sensitive laboratory (immunoblot) and visual tion. Most frequent radiologic lung lesions are nodules, cavitations as
(CT and MRI) diagnostic methods, lead to the diagnosis of tuberculosis. well as consolidations often suspected to represent neoplasia. Thus his-
topathology coupled with molecular pathogen detection as used in our
cases represents an important diagnostic measure to verify this potentially
PS-08-009 life-threatening disease.
Inflammatory pseudotumour of the chest - a medical conundrum
solved with 16S rRNA gene sequencing
M. Zacharias1, L. Brcic1, K. Kashofer1, G. Gorkiewicz1 PS-08-011
1
Institute of Pathology, Medical University of Graz, Austria Histobacterioscopy studies in tuberculosis
V. Zinserling1,2, M. Agapov2, N. Semenova1
1
Background & Objectives: Inflammatory pseudotumour (IP) is an ex- VA Almazov Research Center, Russia, 2 Saint-Petersburg University,
ceedingly rare benign condition that often presents as a locally invasive Russia
mass, most often occurring in the lungs and the orbit. IP is named for its
ability to mimic invasive malignancies on clinical presentation, imaging, and Background & Objectives: Histobacterioscopic studies of
histology. Idiopathic soft-tissue inflammation is thought to be the cause of IP. Mycobacteria tuberculosis (M) play an important role not only in practi-
Methods: Culture-independent, panbacterial (16S rRNA gene) sequenc- cal ±diagnostics but also in understanding of pathogenesis of tuberculo-
ing resolved with next generation sequencing was performed on resected sis. There is practically no information about tissue forms of M in differ-
tissue of IP. ent clinical situations. Our aim was to reveal M in paraffin slices with the
 Virchows Arch

help of different staining in deceased from different forms of tuberculosis (Termo, PA1-7231; PPD) serum against protein antigen B. We considered
(T) number, form and localization of M.
Methods: We investigated 24 autopsy cases of fibrous-cavernous T (FCT) Results: In cases with FCT were typical structural changes with
with long time treatment and 8 cases of T complicating HIV infection in expressed granulomatous reaction. In cases of T complicating HIV
AIDS stage which received no antituberculous medicaments. Paraffin slices alterative and exudative lesions were dominating. Results of
were stained by H-E, Ziehl-Neelsen, auramin-rodamin (luminescent micros- histobacterioscopic studies are presented in the table.
copy) and IHC with Mycobacterium tuberculosis Polyclonal Antibody Percentage of different forms of M in 10-50 view fields

Ziehl-Neelsen Auramin-rodamin IHC

rods cocci irreg rods cocci irreg rods cocci irreg

FCT 88,13±2,14 9,33±1,17 2,5±1,28 64,38±4,24 27,29±3,84 8,33±1,48 57,29±2,78 28,71±2,31 14±1,55
HIV 93,13±2,16 5,38±2,0 1,5±0,89 86,75±2,40 8,13±2,34 5,13±1,04 79±2,64 12,75±2,13 8,25±0,87

In both groups M were located either extracellularly or on the cell surface. the content. Most cases (63.7%) included the diagnosis and some of them
Conclusion: We demonstrated that M are characterised by morpho- (13.5%) were quiz.
logical polymorphism more distinct in the patients, which received Conclusion: - #FNAFriday hashtag has been adopted by the cytopathol-
long time treatment. Cocci and irregular forms are better revealed by ogy community with robust engagement and continued growth in usage.
auramin-rodamin and ICH than by Z-N stain. Exclusive extracellular - Images are central to these posts, and correlation with gross findings,
localization of M requests reconsideration of certain aspects of path- radiology, and ancillary studies is included.
ogenesis of T. - It results an effective way for cytologists to share knowledge and helps
bring awareness of the FNA as an effective method for diagnosis.

Monday, 9 September 2019, 09:30 - 10:30, Agora 3

PS-09 | IT in Pathology PS-09-002
Electromyographic analysis of muscle activation while using differ-
ent input devices in digital pathology
PS-09-001 E. Alcaraz-Mateos1, S. Mèndez-Ríos2, I. Martínez González-Moro2, E.
#FNAFriday: how cytopathologists learn, teach and share knowledge Poblet3
on Twitter 1
University Hospital Morales Meseguer, Murcia, Spain, 2 Department of
E. Alcaraz-Mateos1, J. Temprana-Salvador2, T. Labiano3, I.J. Expósito- Physiotherapy, University of Murcia, Spain, 3 Department of Pathology,
Afonso4, L. Pijuan5 , Z. Baloch6 , M.Y. Fuller 7 , V. Fritzburg8 , E. Reina Sofía University Hospital, Murcia. Faculty of Medicine, University
Madrigal9, V. Walavalkar10, X.". Jiang11 of Murcia, Spain
1
University Hospital Morales Meseguer, Murcia, Spain, 2 Vall Hebron
University Hospital, Barcelona, Spain, 3 Hospitalary Complex of Background & Objectives: Dealing with digital pathology implies an
Navarra, Pamplona, Spain, 4 University Hospital of Canarias, Tenerife, adaptation to the digital environment and the digital image. The input
Spain, 5 Hospital del Mar, Barcelona, Spain, 6 Hospital of the University device traditionally used for whole slide image (WSI) controlling is the
of Pennsylvania, Philadelphia, USA, 7 Children's Hospital of Pittsburgh conventional mouse, but some other devices are also available. The aim
of UPMC, USA, 8 Rutgers, the State University of New Jersey, USA, of this study is to assess the pattern and the amount of muscle activity of
9
Massachusetts General Hospital, Boston, USA, 10 University of the arm while using different input devices and to improve the knowl-
California San Francisco, USA, 11 Duke University Hospital, edge, from an ergonomic point of view, of the human-computer
Durham, USA interaction.
Methods: A comparative study of 10 different input devices (conven-
Background & Objectives: Twitter is a social media network used tional and vertical mouse, three trackballs, Ergopointer TM,
by medical professionals. Hashtags are used to organize posts by Rollermouse TM, optical pen mouse, touchpad, Leap Motion TM)
topic. #FNAFriday is a hashtag created by one of the authors to was carried out. Six medical students, familiarized with WSIs, per-
share educational fine needle aspiration (FNA) cytopathology formed a standardised circuit using a Fitts’ Law based tissue array
cases. This study aims to review the tweets tagged with digitized at 20x. Electric activity of seven upper limb muscles (ad-
#FNAFriday to assess impact/usefulness on the cytopathology ductor pollicis, extensor pollicis longus, extensor digitorum, flexor
community. digitorum, middle deltoid, upper trapezius, middle trapezius) was
Methods: The Twitter search engine was used to review all tweets registered using a surface electromyography.
tagged with #FNAFriday (April 2015- February 2019). The follow- Results: Muscle activity (relativized with respect to repose) was
ing data were collected: author, date, pictures, stains, ancillary found to be different when using each of the input devices: blue
techniques, subspeciality, comments, retweets, and likes, among trackball (176%), Rollermouse (180%), Ergopointer (204%), conven-
others. tional mouse (228%), and vertical mouse (244%) were the ones
Results: A total of 349 original tweets (11256Likes/7099Retweets/ which demanded less activity, while optical pen mouse (323%),
1208Comments) were collected from 47 accounts. The most represented Leap Motion (359%), black trackball (369%), red trackball (539%),
subspecialties were endocrine, gastrointestinal, and head/neck. The aver- and the touchpad (593%) were the ones which required greater mus-
age number of pictures was 3.22/Tweet and the most frequent stain was cle mobilization. Adductor pollicis was the most activated muscle
Papanicolaou, followed by Romanowsky-type stains, and during the exercise.
hematoxylin&eosin (50%/43%/19%, respectively). Cell block (14%), Conclusion: Variability between the use of compared devices and muscle
histologic correlation (10%), immunohistochemistry (8.6%), molecular activity was found. Long-term use could produce different degrees of
tests (2%), gross pictures (4.6%) and radiology (3.4%) were also part of muscular fatigue.
Virchows Arch

Even though the election of an input device is a matter of personal pref- Methods: A Knife-Edge Scanning Microscope (KESM), developed by
erence, it is important to analyse its impact on ergonomics. 3Scan (San Francisco, CA, USA), was used to digitize a whole-mount,
Muscle activity should be integrated together with other human-factor H&E stained, formalin-fixed paraffin-embedded human tissue specimen
aspects since to achieve a holistic approach. obtained from the Radboudumc (Nijmegen, The Netherlands). Sparse
manual annotations of 5 tissue types (tumour, stroma, muscle, healthy
glands, background) were provided using KESM data to train a
PS-09-003 convolutional neural network developed by the Computational
RCPath validation protocol for digital pathology stage 1: our expe- Pathology Group (Radboudumc) for semantic segmentation of the colo-
rience in a large tertiary academic centre rectal carcinoma tissue. A three-dimensional visualization was generated
M. Elshiekh1, M. Munonyara1, C. Wright1 using 3Scan’s proprietary visualization pipeline.
1
North West London Pathology - Imperial College Healthcare NHS Results: The convolutional neural network was used to process roughly
Trust, United Kingdom 1200 slices of KESM data. The stitched and rendered segmentation maps
demonstrate the formalin-fixed paraffin-embedded carcinoma of approx-
Background & Objectives: We present our experience conducting val- imately 5 millimeters in depth. As shown in the figure, the tumour inva-
idation training set phase 1 according to the Guidelines for Digital sive margin can be seen advancing into the surrounding tumour stroma.
Pathology protocol published by the Royal College of Pathologists. Conclusion: Based on our findings, we were capable of training a segmen-
Methods: Thirty histopathology consultants covering ten histopathology tation model on the 3D KESM data to create an accurate representation of an
subspecialties were invited to partake. Of these, fifteen pathologists entire formalin-fixed paraffin-embedded colorectal carcinoma tissue block
reporting eight subspecialties (gastrointestinal, gynaecological, pulmo- segmented into five tissue classifications. Going forward, this can have much
nary, urological, renal, neuropathology, head & neck and breast) partici- broader implications on the research and understanding of invasive tumours.
pated. Pathologists viewed digital slides first and recorded their diagnoses
and confidence level. Glass slides for the same cases were then immedi- Supported by Dutch Cancer Society.
ately examined and any change in diagnoses was recorded as well as
confidence levels in glass slide diagnoses. The preferred diagnosis meth-
od for each case was also noted. PS-09-009
Results: A total of 183 slides were reviewed generating 552 responses. Artificial intelligence a supporting tool for automation and
The mean diagnostic concordance was 96%. Discordances were minor standardisation of the Gleason grading system
and none were clinically significant. The mean diagnostic confidence was F. Marginean1
1
6.6 for digital and 6.9 for glass diagnoses. In 19% of responses, pathol- Lund University, Department of Urology, Sweden
ogists preferred glass slides while the digital method was favoured in 2%.
There was no preference in the majority of responses recorded (79%). Background & Objectives: Prostate cancer (PCa) is the most widely
Conclusion: We learnt the following from phase 1 validation: diagnosed cancer worldwide. Correct identification of the stage, quanti-
• Tissue sampling (size and thickness) and quality of slide preparation fication on histological preparations, using Gleason grading, is essential
impact digital scanning procedures. for diagnosis with strong implications in the treatment options, outcome
• Additional time required by scientific and medical staff to undertake and predict factors. A great interest is in the automation and
phase 1 validation must be considered. standardisation of the Gleason grading system based on lack of patholo-
• Integration of digital pathology systems with the department’s LIMS gists, time-consuming and low reproducibility. Using artificial intelli-
system is crucial to maximize efficiency. gence (AI) we have developed an algorithm, based on convolutional
• Digitizing pathology services offers safety, efficiency and workflow neural networks.
benefits. Methods: The prototype algorithm was trained with 317 haematoxylin &
• Insights learnt can help with preparing a better business case for eosin-stained PCa biopsies from Malmö University Hospital digitally
digitization. scanned and annotated by two experienced uropathologists. The proto-
We are grateful to Philips who supplied scanners and digital support. This type algorithm was trained to detect the benign and cancerous areas and
work wouldn't have been possible without support of NWLP scientific distinguish between Gleason grades 3, 4 and 5. The prototype algorithm
and consultant staff. was tested and validated on the 36 biopsies. The algorithm was adjusted,
re-trained on the 100 haematoxylin & eosin-stained PCa biopsies and
improved until satisfactory result was obtained.
PS-09-005 Results: The algorithm was able to discriminate between cancerous and
A colorectal carcinoma in 3D: merging knife-edge scanning micros- non-cancerous areas with a Pearson correlation between pathologist and
copy and deep learning algorithm of r2= 0.94. The algorithm could also satisfactorily detect dif-
T. Haddad1, N. Farahani2, J. Bokhorst1, F. Doubrava-Simmer1, M. ferent Gleason patterns: (r2= 0.75), Gleason grade 4 (r2= 0.43) and
Goodman2, F. Ciompi1, I. Nagtegaal3, J. van der Laak1 Gleason 5 (r2= 0.83). Overall diagnosis estimated by the algorithm was
1
Radboud University Medical Center, The Netherlands, 2 3Scan, correct on 80% of the tested slides.
USA, 3 Department of Pathology, Radboud University Medical Centre, Conclusion: Artificial Intelligence propose a supporting tool for automa-
Nijmegen, The Netherlands tion and standardisation of the Gleason grading system in the digital
pathology era. It promise to improve reproducibility, reduce interobserver
Background & Objectives: A three-dimensional visualization of a hu- variability and time-consuming.
man carcinoma could provide invaluable diagnostic information and re-
define how we perceive and analyse cancer invasion. As deep learning
begins automating the diagnostic workflow and cutting-edge microscopy PS-09-010
provides unprecedented ways of visualizing tissue, combining these Should I try to learn pathology from YouTube? A medical student's
methodologies could provide novel insight into malignant tumours and critical journey into learning general pathology on YouTube
other pathologic entities. By combining Knife-Edge Scanning J. Melo1, G. Guerra Moita2, G. Bitu dos Santos Ponte2, L. Matias
Microscopy with convolutional neural networks, we set out to visualize Marques2, V.M. Maia Amorim De Morais2, C. Alves Carneiro2, H.
an entire three-dimensional colorectal carcinoma segmented into specific Castelo Branco Roque2, V. Feitosa Muniz2, D. Nunes Oliveira1, M.
tissue classifications. Luiz Balancin3
 Virchows Arch

1
Department of Pathology, Postgraduate Program in Public Health, images with the presence of “open glands” (mag.x100) in PATH-DT-
Faculty of Medicine, University of Fortaleza, Brazil, 2 Faculty of MSU dataset.
Medicine, University of Fortaleza, Brazil, 3 Pathology Division, Clinics
Hospital, Faculty of Medicine, University of São Paulo, Brazil
PS-09-012
Background & Objectives: Pathology teaching in Brazilian Medical Using deep neural network to count Ki-67 positive cells in neuroen-
Schools is a challenging scenario. The discrepancy between scarce time docrine tumours of the gastrointestinal tract
resources available and its cardinal role in Medicine demands innovative N. Mola1, S. Leh1
1
teaching tools. Students, as active learners also rely on non-orthodox Haukeland University Hospital, Norway
online methods, from scientific material to YouTube videos. To evaluate
the nature and quality of information freely available on YouTube about Background & Objectives: Calculation of the Ki-67 index in neuroendo-
basic pathology, directed to students. To engage medical students into a crine tumours (NET) of the gastrointestinal tract is time consuming.
critical review of pathology concepts by encouraging them to screen these Automatic quantification of biomarker expression is a typical application of
videos for mistakes. digital pathology. In the present study a cloud based machine-learning plat-
Methods: Second to Fourth year medical students evaluated YouTube form, Aiforia™, was used to train a deep convolutional neural network
videos from major Brazilian Portuguese speaking channels and gone (CNN) in order to detect Ki-67 positive tumour cells in gastrointestinal NETs.
through a basic pathology concepts check-list for errors. Videos and stu- Methods: 29 digital slides of NETs (resolution 0.23 μm/pixel) were used
dent annotations were reviewed by practicing pathologists. as training data set. The images were uploaded to the Aiforia™ platform.
Results: 65 videos were viewed by the students and reviewed, ranging The algorithm was trained by supervised learning. The algorithm
from 2-82 minutes of duration (median 15 min); views ranged from 145 consisted of two layers. The first layer detected tumour regions and the
to 1026235; subscribers from 20 to 1611416. Authors were medical stu- second layer segmented positive and negative tumour cell nuclei within
dents (23), physicians (16, six pathologists), veterinary physicians (2), the first layer. The performance of the algorithm was initially tested in
others with a biomedical background (19) and undisclosed (5). Four non-annotated areas of the training data set.
channels were linked to academic Institutions. Major errors were evi- Results: The interface for developing a CNN algorithm on the Aiforia™
denced in 7 videos (44%), minor in (56%); academia-related channels platform was intuitive and user friendly. Erroneous detection of mucosa
evidenced less misconceptions than general channels (p=0.04). There was epithelium as tumour was overcome by additional annotations in order to
no statistical correlation between errors and the amount of views or sub- represent all the possible variations of tumour cells as target and mucosa
scribers (p=0.99), although one of the most influent channel (over 315k epithelium as background. In the second layer, cell nuclei segmentation
subs) had major and minor errors was overall adequate, however especially overlapping nuclei continue to
Conclusion: YouTube is not a reliable source of information for technical be an intricate task.
knowledge, although this kind of activity was engaging as a “teaching Conclusion: We present an easy to use machine-learning platform which
from bad examples” by medical student’s perception. has the potential to assist the pathologist in the calculation of the Ki-67
index in NETs. For a final evaluation an independent test set will be used
and the model’s results will be compared to the ground truth, manual
PS-09-011 counting by a pathologist.
Application of convolutional neural networks for glands instance
segmentation in the images of colon epithelial neoplasms
I. Mikhailov1, A. Khvostikov1, A. Krylov1, N. Oleynikova1, P. Malkov1, PS-09-013
O. Kharlova1, N. Danilova1 The new generation of AI tools: allowing pathologists to design their
1
Lomonosov Moscow State University, Russia own algorithms
J. Gildenblat1, C. Sagiv1, N. Sagiv1, I. Ben Shaul1
1
Background & Objectives: There are difficult tasks in the diagnosis of DeePathology.ai, Israel
colon epithelial neoplasms: lack of quantitative criteria of basal dilation of
the crypts and spread of the serration, determination of potential malig- Background & Objectives: Digital pathology is the enabler for computer
nancy. Automatic mucous glands segmentation using a convolutional vision and deep learning algorithms. In the last few years many companies
neural network (CNN) is the first step to real diagnostic algorithm offer dedicate algorithms for various tasks in pathology that pathologists and
development. researchers can use. In many cases, especially in pharma research, patholo-
Methods: We propose a two step algorithm for glands segmentation. The gists would like to design their own algorithms according to their data and
first step produces semantic segmentation using a UNet-based CNN, needs. The aim of the DeePathology AI Platform is to provide pathologists
while the second performs gland instance segmentation using a novel with the ability to design customized algorithms on their own data. This
CNN architecture that predicts parameters for active contour model. approach can bridge the gap between the expert pathology knowledge and
This allows to segment each individual gland. We have designated state of the art computer vision and machine learning capabilities.
closed-contour glands and “open glands” (glands with open contour). Specifically, we plan to discuss the Cell Detection problem. The
Results: The network was first trained on Warwick-QU dataset (165 im- DeePathology.ai Cell Detection Studio is a do it yourself tool for pathol-
ages), fine network tuning was performed on the collected PATH-DT-MSU ogists to train deep learning cell detection algorithms on their own data.
dataset (19 images, colon biopsy material). 12 images were hyperplastic Using this tool, deep learning cell detection solutions can be easily created
polyps; 6 images were SSA/P and one was normal colon tissue. by the pathologist very quickly.
Our segmentation algorithm is characterised by Dice coefficient 0.87 on Methods: Common problems in the process of developing AI solutions
Warwick-QU and 0.78 on PATH-DT-MSU dataset. Dice coefficient de- for the medical field are highly unbalanced datasets on one hand and
creased because of presence of «open glands» and the glands with ad- limited annotation resources on the other hand.
hered contours. The use of Active Learning can dramatically help with both issues.
Conclusion: It is necessary to create alternative collections of annotated The task of Cell Detection is very important in digital pathology. For
histological images of colon epithelial neoplasms and to use full-size example, analyzing the quantity and density of immune cells can provide
images obtained in the pathology examination of the real colon biopsies important indications on the progress of cancer.
because images are cut off and only contain closed-circuit glands This is a tedious task when manually done by pathologists and thus,
(mag.x200, x400) in the Warwick-QU. In contrast there are full-size real automating this process is desirable.
Virchows Arch

Automating cell detection requires annotating large amounts of data, of Medical Research, University Medical Centre Mannheim, University of
which is usually very unbalanced. Heidelberg, Germany, 3 Institute of Pathology and Nephropathology
In the talk we will use the example of the DeePathology.ai Cell Detection Section, University Hospital Hamburg Eppendorf, Germany, 4 Institute of
Studio to demonstrate how Active Learning can be used for medical Pathology, University Medical Centre Mannheim, University of Heidelberg,
imaging annotation. Germany
We will also present our approach for using active learning with unbal-
anced datasets. Background & Objectives: Myeloproliferative neoplasms (MPN) and
Results: The Cell Detection studio was applied to various use cases of myelodysplastic/ myeloproliferative neoplasms (MDS/MPN) represent
Cell Detection tasks. clonal hematopoietic diseases characterised by proliferation of myeloid
We show how the pathologist can create annotated data set of thousands cells. The spectrum of glomerular alterations associated with MPN has
of examples within hours and how a customized cell detection algorithm been addressed by only few reports. For MDS/MPN no data is available.
is created along with a report on number of cells, their features and more. Our aim was to systematically evaluate kidney biopsies performed in
Conclusion: Digital pathology is a game changer. It is also an enabler for patients with known MPN or MDS/MPN.
the design of algorithms. Methods: Retrospective analysis of kidney biopsies in patients with the
The challenge is to bring AI capabilities to the hands of pathologists and diagnosis of MPN or MDS/MPN was performed. The cohort (n=27)
provide genuine Pathologist Assistant System. encompassed patients with chronic myeloid leukemia (CML, n=5), poly-
The DeePathology AI platform allows pathologists and researchers to cythemia vera (PV, n=8), primary myelofibrosis (PMF, n=4), essential
design and use state of the art Deep Learning algorithms without being thrombocythemia (ET=2) and chronic myelomonocytic leukemia
AI experts. (CMML, n=3) as well as MPN or MDS/MPN without further specifica-
tion (MPN=4, MDS/MPN=1). In order to control for age-related phenom-
ena, the findings were compared to age- and sex-matched zero-time graft
Monday, 9 September 2019, 09:30 - 10:30, Agora 3 biopsies.
PS-10 | Nephropathology Results: Patients manifested with proteinuria (89%), partially in nephrot-
ic range (37%), hematuria (64%) and kidney failure (100%). In compar-
ison to controls, MPN and MDS/MPN patients showed a significantly
PS-10-001 higher ratio of sclerosed glomeruli and mesangial expansion. Moreover,
Eradication of Helicobacter Pylori alleviates proteinuria in Primary ultrastructural signs of endothelial damage and subendothelial edema
Focal Segmental Glomerulosclerosis - a case series represented frequent findings (89%). Mesangiolysis (19%) and other fea-
M. Bosnjak1, N. Kojc1, A. Aleš Rigler2 tures compatible with thrombotic microangiopathy (33%) constituted
1
Institue of Pathology, Faculty of Medicine, University of Ljubljana, other less frequent findings. Extramedullary hematopoiesis was present
Slovenia, 2 Department of Nephrology, University Medical Center in 3 cases (11%).
Ljubljana, Slovenia Conclusion: Patients with MPN and MDS/MPN show glomerular scar-
ring that exceeds age-related phenomena. Some of the biopsies indicate
Background & Objectives: Along with chronic gastritis, there is evidence that a low-level chronic endothelial damage or thrombotic microangiop-
that Helicobacter Pylori (HP) is associated to several extra-digestive pa- athy might represent the mechanisms resulting in mesangial and glomer-
thologies A few studies therefore reported both the presence of HP antigens ular sclerosis. In addition to the anti-neoplastic therapy, optimization of
in the glomeruli and a beneficial effect of HP eradication therapy on daily risk factors for kidney failure and early recognition of renal complication
proteinuria in cases of membranous nephropathy (MN). should be recommended.
The focus was to demonstrate the yet unaccounted-for ameliorating effect
of HP eradication on clinical course in three patients with Focal
Segmental Glomerulosclerosis (FSGS), an important cause of nephrotic PS-10-003
syndrome in adults. Proposal for a semi-quantitative algorithm functional in the assess-
Methods: The patients were selected based on kidney biopsy findings ment of lupus nephritis lesions
(proven FSGS), presence of HP gastritis on gastric biopsy as well as I.D. Caruntu1, T. Azoicai1, E.R. Avadanei1, L. Lozneanu1, S. Giusca1
exclusion of significant comorbidities. A triple eradication therapy was 1
"Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania
subsequently warranted. The follow-up was clinical.
Results: Two of the patients had concomitant HP gastritis at presentation Background & Objectives: The study points out the histological chang-
and the third was in partial remission on combined immunosuppression es in lupus nephritis (LN), aiming to refine the assessment of specific
when HP gastritis was diagnosed. Immunosuppression with prednisone lesions defined by ISN/RPS Classification.
(0.8mg/kg) was administered along with HP eradication therapy, which Methods: We analysed 53 renal biopsies diagnosed as LN by light
resulted in rapid and long lasting complete remission. None of the patients and immunofluorescence microscopy. A semi-quantitative algorithm
relapsed to date and none requires maintenance immunosuppression. for corpuscular, tubular, interstitial and vascular lesions was con-
Conclusion: Contrary to MN, the positive influence of HP eradication on ceived and applied. Score values between 0 and 3/4 was done for
daily proteinuria values has not been observed previously in FSGS. Given the severity of each type of lesion – with a final score for renal
that spontaneous remission rate is <5% in nephrotic FSGS patients and that corpuscles (RC_S, maximum value of 33) and tubulo-interstitial
relapses are relatively common (25-36%), HP might play a yet unaccounted- components (TI_S - maximum value of 18). NIH activity and chro-
for role in disease pathogenesis. We therefore recommend HP-oriented di- nicity indices were also settled.
agnostic methods when FSGS patients complain of dyspepsia. Results: The algorithm revealed a large variability of lesions’ extension
and gravity within each class of LN, supporting the active and/or chronic
status that complete diagnosis. Hence, for 2 cases in class II, RC_S values
PS-10-002 were 3 and 5, and IT_S was 2. 4 cases in class III had RC_S values of 8-9
Glomerular disease associated with myeloproliferative and and IT_S of 3. 19 cases in class IV presented RC_S values between 8-19
myelodysplastic/myeloproliferative neoplams and IT_S between 4-11. 24 cases in class V showed RC_S between 5-25,
M. Buettner-Herold1, C. Sticht2, T. Wiech3, S. Porubsky4 and IT_S of 0-13. For 6 cases in class VI, RC-S values were 20-22, and
1
Department of Nephropathology, Institute of Pathology, Friedrich- IT_S were 9-14. Our results indicated significant correlations between the
Alexander-Universität Erlangen-Nürnberg (FAU), Germany, 2 Center RS-S and IT-S values and the NIH activity and chronicity indices.
 Virchows Arch

Conclusion: Our algorithm offers a reproducible tool for a more objec- related to warfarin use and 1 to dabigatran use. Only three had
tive evaluation of renal biopsies and the differentiation between classes the data about anticoagulant therapy written on requisition form at
and subclasses of LN. Larger studies are compulsory for proving the the time of biopsy.
clinical significance of the proposed scores. All kidney biopsies showed acute tubular injury associated with
occlusive RBC casts. 5 of them had underlying undiagnosed mild
IgA nephropathy. There was disproportion between the number of
PS-10-004 RBC tubular casts, the degree of acute tubular injury and the
Kidney biopsy codes for pathologists, status update degree of glomerular injury by IgA nephropathy.
A. Dendooven1, M. Helbert2,3,1, H. Peetermans2, T. Nguyen4, S. Leh5 Conclusion: Pathologists should be aware of this entity and ARN
1
University of Antwerp, Belgium, 2 Ziekenhuis Netwerk Antwerpen should be suspected when there is disproportion between the
(ZNA), Belgium, 3 University Hospital Antwerp (UZA), Belgium, number of RBC tubular casts and the severity of underlying kid-
4
UMC Utrecht, The Netherlands, 5 Department of Pathology, ney disease, and seek clinical data regarding anticoagulant thera-
Haukeland University Hospital, Norway py. Clinicians should closely monitor kidney function in patients
on anticoagulant therapy.
Background & Objectives: Kidney biopsy registries all over the world
benefit research, teaching and health policy strategy. Because registries
are mainly using locally developed coding systems for pathology diag- PS-10-006
noses; comparison, exchange or accumulation of data are hampered. IgG4 related kidney disease: report of 21 cases
Consequently, there is great need for a standardised, interoperable coding H. Gakiopoulou1, K. Stylianou2, H. Theodoropoulou3, S. Havaki4, D.
system. Pouloudi5, A. Stofas6, D. Petras7, A. Gerakis8, D. Vlahakos9, D.
The “Kidney Biopsy Codes (KBC)” project aims to provide a complete Goumenos10, E. Daphnis2, H.M. Moutsopoulos11
1
and structured set of terms and codes applicable to every non-neoplastic 1st Department of Pathology, School of Medicine, The National and
kidney biopsy. Kapodistrian University of Athens, Greece, 2 Department of
Methods: Work package 1 (WP1) investigated coding praxis of kid- Nephrology, Heraklion University Hospital, Crete, Greece, 3 Renal
ney biopsy registries and analysed strengths and weaknesses of Unit, General Hospital "Alexandra", Athens, Greece, 4 Department
established international coding systems. WP2 developed principles of Histology and Embryology, School of Medicine, National and
for the KBC system during a consensus workshop. WP3 addresses Kapodistrian University of Athens, Greece, 5 First Department of
the technical design and generates the KBC as such. WP4 will Pathology, Medical School, National and Kapodistrian University of
conduct a review process. WP5 will build structures for mainte- Athens, Greece, 6 1st Department of Pathology, School of Medicine,
nance and further development. The KBC system is built and tested The National and Kapodistrian University of Athens, Greece,
7
via an international team of pathologists, nephrologists, coding spe- Nephrology Department, Hippokrateio Hospital, Athens, Greece,
8
cialists and IT professionals. Department of Nephrology, Hygeia Hospital, Athens, Greece,
9
Results: WP1 identified multiple problems with existing coding Division of Nephrology, Attikon University Hospital, National and
systems. Key principles for the new KBC system (WP2) were to Kapodistrian University of Athens Medical School, Greece,
10
code for more than one morphological pattern and to code along Department of Nephrology, University Hospital of Patras, Greece,
11
multiple axes. Based on these principles a hierarchical coding sys- Department of Pathophysiology, School of Medicine, National &
tem was drafted (WP3) where both morphological pattern(s), biop- Kapodistrian University of Athens, Greece
sy diagnosis and a certainty factor are elements building up the
code. Background & Objectives: The spectrum of renal involvement in the
Conclusion: The KBC project aims to provide a comprehensive, gener- context of IgG4 Related Disease (IgG4RD) is not fully elucidated.
ally applicable, interoperable and easy-to-update coding system for kid- The aim of this study was to record and analyse our experience on
ney biopsy diagnoses. A code list is drafted that contains several axes and the basis of renal biopsies diagnosed as renal involvement in the
thus ensures for tagging of both ordinary and unconventional cases, even context of IgG4RD.
when the diagnosis is unclear. Methods: Light microscope including histochemistry, immunohisto-
chemistry for IgG/ΙgG4, PLA2R and THSD7A, immunofluorescence
and electron microscope.
PS-10-005 Results: During a 5 year period, 22 renal biopsies from 21 patients all
Anticoagulant-related nephropathy: report of 6 cases over Greece, were diagnosed as having renal involvement in the
M. Frelih1 context of IgG4RD. There were 14 male and 7 female patients with
1
Institute of Pathology, Medical Faculty Ljubljana, University of a mean age of 67 years (range: 45-84 years). Most patients presented
Ljubljana, Slovenia with an acute or progressive deterioration of their renal function,
often on a background of an unexplained chronic renal failure.
Background & Objectives: Anticoagulants are prescribed for num- Only three patients had a clinical suspicion of IgG4RD based either
ber of thromboembolic disorders. With their use comes the risk to a measurement of serum IgG4 and/or to a previous biopsy in
for hemorrhage. They can cause glomerular hemorrhage and renal another organ showing IgG4RD.The renal biopsy findings can be
tubular obstruction by red blood cell (RBC) casts with subsequent divided into 3 groups: a) IgG4 related tubulointerstitial nephritis
deterioration of kidney function. Another mechanism of injury by (TIN) without glomerulopathy (11 patients), b) IgG4 related TIN
RBC casts is heme toxicity. In literature, most common and first concomitant with glomerulopathy (7 patients) and c) glomerulopathy
described anticoagulant causing this type of kidney injury is war- without TIN (3 patients). The most common glomerulopathy con-
farin, but lately also novel oral anticoagulants are found to be the comitant with TIN was membranous glomerulopathy (MG). All pa-
cause. tients in the third group had a MG IgG4 (+)/PLA2R (-)/THSD7A(-)
Methods: Here, we report pathological findings in 6 cases of and compatible clinical & laboratory findings.
anticoagulant-related nephropathy (ARN) that were found in our database Conclusion: Diagnosis of ΙgG4RD is often first established by the
during years 2014-2018. renal biopsy. TIN with or without glomerulopathy or glomerulopa-
Results: All cases presented with acute kidney injury, 5 of them thy alone consist possible ways of renal involvement in the context
also had preexisting chronic kidney disease. Of 6 cases, 5 were of IgG4RD.
Virchows Arch

PS-10-007 General Hospital "Alexandra", Athens, Greece, 6 Renal Unit, General

The REDD1/autophagy pathway mediates the release of TF- and IL- Hospital "Alexandra" Athens, Greece, 7 Department of Nephrology,
17A-bearing Neutrophil Extracellular Traps (NETs) in human Hygeia Hospital, Athens, Greece, 8 1st Department of Pathology, School
Systemic Lupus Erythematosus (SLE), promoting of Medicine, The National and Kapodistrian University of Athens,
thromboinflammation and fibrosis Greece, 9 Nephrology Department, Hippokrateio Hospital, Athens,
E. Frangou1, H. Gakiopoulou2, A. Chrysanthopoulou3, K. Kambas3, A. Greece, 10 Division of Nephrology, Attikon University Hospital,
Mitsios3, I. Angelidou3, T. Arambatzioglou3, G. Bertsias4, P. Verginis5, National and Kapodistrian University of Athens Medical School,
K. Ritis3, D.T. Boumpas6 Greece
1
Department of Nephrology, Limassol General Hospital, Cyprus &
Medical School, University of Cyprus, Nicosia, Cyprus & Biomedical Background & Objectives: To present a case series of 18 patients with a
Research Foundation of the Academy of Athens, Greece, 2 1st diagnosis of secondary oxalate nephropathy attributed either to enteric
Department of Pathology, School of Medicine, The National and malabsorption (gastric bypass, chronic pancreatitis, bariatric surgery, pan-
Kapodistrian University of Athens, Greece, 3 Medical School, creatic adenocarcinoma, hemicolectomy) or to increased intake of oxalate
Democritus University of Thrace, Alexandroupolis, Greece, precursors (vitamin C, oxalate-containing foods).
4
Rheumatology, Clinical Immunology and Allergy University of Crete Methods: In a 5 year period, we identified 18 renal biopsies (investigated
School of Medicine, Heraklion, Greece, 5 Biomedical Research with light microscope, immunofluorescence and electron microscope-
Foundation of the Academy of Athens, Greece, 6 Biomedical Research when needed), with a diagnosis of secondary oxalate nephropathy.
Foundation of the Academy of Athens, Greece & 4th Department of There were 11 male and 7 female patients aged 40-88years (mean:
Medicine, "Attikon" University Hospital, Greece & Joint 68,4years).
Rheumatology Program, National and Kapodistrian University of Results: All patients presented with unexplained acute renal failure (mean
Athens Medical School, Greece Cr: 7,7mg/dl, range: 3.1-23mg/dl, median:6mg/dl), without significant pro-
teinuria, without active urine sediment. Half of the patients had arterial hy-
Background & Objectives: NET release represents a novel neutrophil pertension and/or diabetes mellitus and/or abnormal BMI. Four of these pa-
effector function in SLE pathogenesis. We investigated the molecular mech- tients showed changes of adaptive focal segmental glomerulosclerosis and/or
anism underlying NET release and how NETs mediate end-organ injury in diabetic nephropathy and/or hypertensive nephrosclerosis. All biopsies
SLE. showed acute tubular injury with abundant transparent crystals into the tubu-
Methods: Serum and neutrophils from healthy individuals and SLE patients lar lumens and into the cytoplasm of epithelial tubular cells, with
(in active disease and in remission) were isolated. Cultures of ex vivo neu- birefringency under polarized light, suggestive of calcium oxalate deposits.
trophils and in vitro stimulation or inhibition studies were performed. In most biopsies rupture of tubular basement membranes was seen. Various
Autophagy levels, NET release and proteins on NETs were studied by im- interstitial inflammation (from scarce to diffuse) with some eosinophils in
munofluorescence, immunoblotting, qPCR and ELISA. The effector func- most cases and various interstitial fibrosis/tubular atrophy (IFTA) were no-
tion of NETs was investigated in a primary fibroblast culture. Kidney and ticed. The outcome of most patients was poor and probably worse in patients
skin biopsies from patients with proliferative lupus nephritis (LN) and active with diabetes mellitus and arterial hypertension.
discoid lupus, respectively, were studied with immunofluorescence. Conclusion: Oxalate nephropathy is not a rare condition among patients
Results: Autophagy is increased in neutrophils from active SLE patients, undergoing renal biopsy for an unexplained acute renal failure with an
leading to increased NET release that is abolished by inactive urine sediment. Clinical suspicion should be raised in the pres-
hydroxychloroquine. Serum from active SLE patients upregulates the ence of risk factors. Histologic recognition is essential to avoid inappro-
hypoxia- and stress-response protein DDIT4/REDD1 in healthy neutro- priate treatments and to guide reversal of the causative factors.
phils, leading to increased autophagy and NET formation. Endothelin-1
(ET-1) and hypoxia-inducible factor-1α (HIF-1α) were key mediators of
this effect. Tissue factor (TF) and interleukin-17A (IL-17A) on SLE PS-10-009
NETs were bioactive, as evidenced by thrombin generation and Clinicopathological characteristics of 3 patients with atypical anti-
activation/differentiation of skin fibroblasts to collagen-producing glomerular basement membrane disease
myofibroblasts. These findings were abolished by HIF-1α inhibition by I. Işık Gönül1, B. Ozbas2, O. Helvaci2, U. Derici2, T. Arinsoy2
1
L-ascorbic acid or ET-1 inhibition by bosentan of in vitro-stimulated Gazi University Medical School Department of Pathology, Turkey,
2
neutrophils, as well as by TF or IL-17A blockade on NETs. TF- and Gazi University Medical School, Department of Nephrology, Turkey
IL-17A-bearing NETs were observed in kidney and skin biopsies from
patients with proliferative LN and active discoid lupus, respectively. Background & Objectives: Anti-glomerular basement membrane disease
Conclusion: The REDD1/autophagy/NET axis is involved in end-organ (anti-GBM) is a rare autoimmune disorder characterised by severe pulmonary
injury and fibrosis in SLE and represents a candidate for drug reposi- and renal involvement in the form of necrotizing crescentic glomerulonephritis.
tioning in SLE therapy. Autophagy-mediated release of TF- and IL-17- Methods: Three cases of anti-GBM disease with atypical clinicopatho-
b e a r i n g N E Ts i n a c t i v e S L E p r o v i d e s a l i n k b e t w e e n logical findings were diagnosed in the last 2 years. Clinical and renal
thromboinflammation and fibrosis, and may account for the salutary ef- biopsy findings of these cases were evaluated.
fects of hydroxychloroquine in SLE. Results: Kidney biopsy findings of these 3 patients were heterogeneous; first
patient’s biopsy revealed proliferative glomerulonephritis with crescents. The
second patient’s biopsy showed nodular glomerulosclerosis with crescents.
PS-10-008 The third patient’s biopsy was characterised by classical necrotizing diffuse
Secondary oxalate nephropathy: a case series of 18 patients crescentic glomerulonephritis. For all patients’ biopsies, the immunofluores-
H. Gakiopoulou1, N. Givalos2, M. Papasotiriou3, K. Stylianou4, H. cence revealed a linear staining with IgG along the glomerular basement
Theodoropoulou5, E. Psimenou6, I. Giatras7, A. Stofas8, D. Petras9, A. membranes. Electron microscopy was not utilized for any of the cases.
Gerakis7, E. Dafnis4, D. Vlahakos10, D. Goumenos3 Anti-GBM antibodies were negative in the serum for the first and third
1
1st Department of Pathology, School of Medicine, The National and patients. The first patient was a 25-year-old male with hemoptysis, darkening
Kapodistrian University of Athens, Greece, 2 2nd Department of General in urine color, and pretibial edema. Despite an aggressive treatment, the
Surgery, General Hospital of Attica "KAT", Greece, 3 Department of patient died with severe ARDS and heart failure. The second patient was a
Nephrology, University Hospital of Patras, Greece, 4 Department of 28-year-old male with weakness, hemoptysis, swelling in the eyes and hands.
Nephrology, Heraklion University Hospital, Crete, Greece, 5 Renal Unit, Anti-GBM antibody was positive in the serum. The patient has been followed
 Virchows Arch

on a thrice weekly hemodialysis program with pulmonary relapse. The third PS-10-016
patient was a 60-year-old male with sore throat, cough and hemoptysis. The Comparative characterics of IgA nephropathy and IgA vasculitis
patient was discharged with twice weekly hemodialysis program. with glomerular extracapillary proliferation in adults
Conclusion: Atypical anti-GBM disease may present itself with non- Y. Rogov1, M. Dmitrieva2, T. Letkovskaya3, V. Savosh3, K. Komissarov4
1
characteristic clinical and unexpected histological features. The first step Belarusian Medical Academy of Postgraduate Education, Belarus,
2
to correct diagnosis is to be aware of the disease. City Clinical Pathology Bureau, Belarus, 3 Belarusian State Medical
University, Belarus, 4 State Institution "Minsk Scientific and Practical
Center of Surgery, Transplantology and Haematology", Belarus
PS-10-011
Tubuloreticular inclusions in renal microvasculature of renal Background & Objectives: Nowadays IgA nephropathy (IgAN) and
allografts IgA vasculitis (IgAV) are considered as local and systemic manifestations
H.J. Jeong1, B.J. Lim1, Y.S. Kim1, K.H. Huh1, S.I. Kim1, M.S. Kim1 of the same entity, associated with IgA deposits in mesangial matrix and
1
Yonsei University, Republic of Korea vascular walls. Glomerular extracapillary proliferation (GEP) can be ob-
served in both of conditions. The aim of this study was to compare
Background & Objectives: Tubuloreticular inclusions (TRIs) may be clinical evidence and morphological features in IgAN and IgAV adult
present in microvasculature of renal allografts, but their significance has patients with GEP.
not been well explored. Methods: All kidney biopsies stained by hematoxylin-eosin, PAS,
Methods: Twenty-six renal allograft cases having TRIs in peritubular Masson trichrome, Congo red, Jones silver have been evaluated on light
capillaries (PTCs) or glomerular endothelial cells (GECs) were reviewed microscopy. Immunofluorescence (IF) staining for IgG, IgA, IgM, C3c,
and correlated with clinical features. TRIs were present in PTCs in 17 C1q, fibrinogen, k and λ light chains was performed on paraffin sections.
cases, in GECs in 7 cases and in both in two cases. All cases were confirmed by dominant/codominant mesangial IgA depo-
Results: The diagnoses were acute or chronic T cell-mediated rejection sition in glomeruli on IF. IgAV patients had extrarenal manifestation (skin
(TCMR) (n=2), suspicious for acute TCMR (n=3), acute or chronic rush, gastrointestinal vasculitis, arthralgia). Median follow up period was
antibody-mediated rejection (AMR) (n=6), combined acute AMR and 14 (6-33) month (range, 25% -75%).
TCMR (n=2), acute tubular injury (n=2), polyomavirus nephropathy (n=2), Results: Among 694 native kidney biopsies examined from 2011 to 2015
IgA nephropathy (IgAN) (n=1), and tubular atrophy and interstitial fibrosis years 29.7% cases (n=206) were diagnosed with IgAN and 2.7% (n=19) -
(n=8). TRIs in PTCs were mostly associated with rejection (n=5), viral infec- with IgAV. Mean age was 34.2±11.7 years. Male prevalence observed 1.9
tions (n=6), or both (n=4), and with peritubular capillaritis. However, TRIs in times often (42/22) in IgAN and 1.8 times (7/4) - in IgAV (p>0.05). The first
GECs were found in diverse conditions and not associated with glomerulitis. group demonstrated GEP in 31.1% (n=64), the second group - in 57.9%
Conclusion: TRIs in PTCs, but not in GECs may be a sensitive indicator (n=11) biopsies (χ2=5.63; р=0.0176). IgAV patients revealed higher percent
for microvascular injury in the context of AMR and viral infection. of cellular and fibrocellular crescents (U=185.0; р=0.038). Crescent devel-
opment risk was 2.75 times higher (95% CI; 1.15-6.55) in IgAV, in contrast
with IgAN. There was no statistically significant difference in proteinuria,
PS-10-014 serum urea and creatinin levels (p=0.569, p=0.590, p=0.540 respectively), as
Renal involvement in familial Mediterranean fever well as in global and segmental glomerulosclerosis and interstitial fibrosis
A.A. Ozagari1, K.G. Eken1, M. Sevinc2, G. Ozcelik3, F. Kabukcuoglu1 percentage (p=0.309, p=0.747, p=0.964 respectively).
1
University of Health Sciences Sisli Hamidiye Etfal Hospital, Conclusion: IgAN and IgAV with GEP are similar by clinical course and
Department of Pathology, Turkey, 2 University of Health Sciences Sisli morphological features. The greater severity of GEP in IgAV was asso-
Hamidiye Etfal Hospital, Department of Nephrology, Turkey, 3 ciated with more frequent patient mortality, but did not affect the need for
University of Health Sciences Sisli Hamidiye Etfal Hospital, kidney replacement therapy.
Department of Paediatric Nephrology, Turkey

Background & Objectives: Familial Mediterranean fever (FMF) is a PS-10-017

hereditary disease with recurrent attacks. One of the complications of M-ToR inhbitors nephrotoxicity: 3 cases series
the disease is amyloidosis which primarily affects the kidneys. Several A. Sanz Zorrilla1, F. Leiva-Cepas1, A. Martínez López1, R. Sánchez
types of glomerular disease can also be seen in FMF, and FMF-related Sánchez1, R. Ortega Salas1
1
glomerulonephritis may be more common than it is thought. University Hospital Reina Sofía, Spain
Methods: This study is a retrospective analysis of data from patients with
FMF undergoing kidney biopsy, over 14 years (2005–2019). Demographic Background & Objectives: Calcineurin inhibitors have been the immu-
data, clinical and pathology findings of these patients were evaluated. nosuppressants of choice in recent decades in kidney transplantation,
Results: Of the 37 patients, 22 (60%) were female and 15 (40%) were however, in recent years, m-ToR inhibitors have replaced them progres-
male with an age range of 5 to 59 years (mean 26 years). The duration of sively due to their lower incidence of side effects. Specifically at the
FMF at the time of biopsy was 2 months to 20 years (mean 6 years). All kidney level, there is a controversy over whether the latter cause an
patients had proteinuria above 0.5 g/24h (mean 3.3g /24h). On micro- increase in proteinuria with long-term glomerular damage.
scopic examination of the renal biopsies 11 (30%) patients were found to Methods: Three cases are presented, the first case is a 40-year-old man
have amyloidosis, 9 (24%) IgA nephropathy, 7 (19%) mesangial prolif- transplanted by CKD secondary to idiopathic haemolytic uraemic syndrome
eration without immun complex deposition, 5 (13%) minimal change and treated with everolimus, which debuts with nephrotic proteinuria two
disease, 2 (5%) focal segmental glomerulosclerosis (FSGS), 1 (3%) mem- months post-transplant. The second case is a 60-year-old woman kidney
branous nephropathy, and 1 (3 %) membranoproliferative glomerulone- transplant 27 years ago for CKD secondary to insulin-dependent diabetes,
phritis (MPGN). One patient had concomitant amyloidosis and IgA which, due to circumstances arising from the pathological process, begins to
nephropathy. be treated with sirolimus, at which time it starts with proteinuria of 8 g / dl.
Conclusion: Spectrum of renal involvement in FMF patients is highly The last case is a 66-year-old woman transplanted by IgA nephropathy and
variable, only 30% of the cases diagnosed as amyloidosis in our series. In treated with m-ToR inhibitors, she also developed proteinuria over time.
patients with FMF and renal involvement, non-amyloid renal lesions are Results: Both biopsies show glomeruli with segmental sclerosis, hyalinosis
not uncommon and should be considered in the differential diagnosis in more evident in the first case, and podocytic hyperplasia more striking in the
addition to amyloidosis. second, with no evidence of acute or chronic rejection in either of the two:
Virchows Arch

1
changes suggestive of nephrotoxicity by m-ToR inhibitors (diagnoses within Institute of Pathology, School of Medicine, University of Zagreb,
the clinical context exposed and supported by immunohistochemical tech- Croatia, 2 Unit of Nephropathology and Electron Microscopy,
niques), and in the first case, with ultrastructural study. Department of Pathology and Cytology, Dubrava University Hospital,
Conclusion: Calcineurin inhibitors produce hypertension and nephrotoxici- Zagreb, Croatia, 3 Department of Nephrology, University Hospital
ty, and although m-ToR inhibitors have been shown to be superior, it has been Merkur, Zagreb, Croatia
proven by their use that they are not free of iatrogenic effects (proteinuria is
the most frequent clinical finding and glomerular sclerosis) the most constant Background & Objectives: Zero-time renal biopsy is biopsy performed
histological finding in proportion proportional to podocyte damage) as evi- before or immediately after the transplantation with the purpose of
denced in our case. Podocyticc desdifferenciation has been proved by specific pathohistological assessment of morphologic characteristics of donated
inmunohistochemical techniques which are not present in the normal adult kidney tissue. Aim of this study was to investigate morphological find-
podocyte. Our three cases as Letavernier. E y cols. cases, show how m-ToRs ings of zero-time biopsies analysed at Unit of Nephropathology and
can produce this kind of podocytopathies. The presence of inmaturity Electron Microscopy at Dubrava University Hospital, Zagreb.
podocytes may cause glomerulosclerosis and be the consequence of de- Methods: Retrospective research of pathology reports was performed for
creased expression of inmunohistochemical markers such a synaptopodin. period from 2006 to 2018. Total of 316 zero-time renal biopsies were
performed in Clinical hospital Merkur (84%) and Clinical hospital Osijek
(16%) and analysed in our department.
PS-10-018 Results: Recipient age ranged from 16 to 84 years (median 51). Acute
Characterisation of acute tubular injury in cholemic nephropathy tubular injury was present in 90% of biopsies, mainly in its moderate form
(bile cast nephropathy) by immunohistochemistry and mass (51%). In 17% of biopsies some form of glomerular pathology was pres-
spectrometry ent. Most common entity was thin glomerular basement membrane (13%)
J. Schmitz1, J. Merl-Pham2, W. Dai1, A. Khalifa1, K. Diahovets1, Y. and followed by diabetic nephropathy (2%), IgA nephropathy (1%),
Mederacke3 , I. Mederacke 3 , T. Feldkamp 4 , U. Kunzendorf 4 , A. thrombotic microangiopathy (0.3%) and immune-complex mediated
Wagner5, N. Richter5, L. Pape6, S. Hauck2, W. Gwinner7, J.H. Bräsen1 glomerulonepritis (0.3%). Chronic changes of tubulointerstitium and
1
Institute of Pathology, Hannover Medical School, Germany, 2 Research blood vessels were evaluated according to Banff criteria. Lowest grades
Unit Protein Science, Helmholtz Centre Munich, German Research of interstitial fibrosis and tubular atrophy (ci0 and ct0) were the most
Center for Environmental Health, Germany, 3 Department of common. In 13% of specimens, arteries showed moderate or severe
Gastroenterology, Hepatology and Endocrinology, Hannover Medical fibrointimal thickening (cv2 and cv3) while arterioles were even more
School, Germany, 4 Department of Nephrology and Hypertension, affected with 36% of specimens showing moderate or severe
University Hospital Schleswig-Holstein, Kiel, Germany, 5 Clinic for arteriolosclerosis (ah2 and ah3).
General, Abdominal and Transplant Surgery, Hannover Medical Conclusion: Zero-time renal biopsy shows morphological condition of
School, Germany, 6 Paediatric Nephrology, Hannover Medical School, transplanted kidney and is of importance for comparison with further protocol
Germany, 7 Department of Nephrology and Hypertension, Hannover or indication biopsies, treatment and diagnostic evaluation and clinical trials.
Medical School, Germany

Background & Objectives: Morphologically, cholemic nephropathy PS-10-021

(CN) is characterised by extensive acute tubular injury (ATI) and bile- Analysis of tubulointerstitial fibrosis in patients with diabetes
stained tubular casts consisting of sloughed epithelial cells and acellular mellitus
material. CN occurs in patients with cholestatic liver disease and is diag- V. Sipovski1, A. Smirnov1
1
nosed by positive Hall’s stain. Recently, we described loss of aquaporin 2 Nephrology Research Institute, Russia
expression in collecting ducts in a small cohort of patients with elevated
bilirubin and CN. Background & Objectives: The progression of diabetic nephropathy
Methods: Now, we characterised ATI in CN by staining for several ATI (DN) often is combined with non-diabetic glomerulopathies (NDGP),
(NGAL, KIM1, FACL4, cCasp3, THP) and recovery markers (Ki67) in which can affect the prognosis and treatment of patients. However, the
39 patients with CN (n=16), oxalate nephropathy (OX-N, n=6), CNI information about such influences is not enough.
(calcineurin inhibitor) toxicity (n=6) and light chain cast nephropathy The objective of such study is to investigate the effect of NDGP on
(CAST, n=11). Biopsies before transplantation (zero-biopsies, n=5) fibrotic processes in kidney parenchyma.
served as controls. Additionally, mass spectrometry (LC-MS/MS) of the Methods: Patients with DN-gr.№1 were divided on gr.№2-“pure” DN
paraffin samples was performed to identify new markers for diagnosis and gr.№3- DN with NDGP. Histopathological analysis (focal sclerosis
and potential targets for therapy. (FS), glomerulosclerosis (GS), hyalinosis of arterioles (GA), severity of
Results: In CN, expression of THP and NGAL was higher than in OX-N leukocyte infiltration in tubulointerstitium (ITIN), peritubular capillaritis
and expression of NGAL and FACL4 was higher than in CAST. More (PTC), tubular atrophy (TA) were performed semiquantitatively,
Ki67 positive tubular nuclei were detected in CN than in CNI toxicity and Immunohistochemistry were performed for α-SMA by EnVision detec-
OX-N. Mass spectrometry showed higher amounts of aldo-keto reduc- tion system for marking of myofibroblasts.
tases in CN samples (up to 200-fold) than in OX-N, CNI toxicity and Results: The 51 patients were in gr. №1, 30 patients in gr. № 2, 21
controls. Currently, immunohistochemistry for verification and patients in gr. №3. The patients with IgA- nephropathy (20 %) were the
localisation of these enzymes in the renal tissue is performed. most common glomerulonephritis (GN) followed by focal segmental
Conclusion: Positive stains of injury markers confirmed the tubulopathy glomerulosclerosis (FSGS)-35%. HCV –associated GN was the most
caused by bile acids. High FACL4 (ferroptosis marker) and Ki67 (prolif- common among secondary GN. No significant between-group differ-
eration marker) expression in CN samples might reflect high turnover and ences were observed with the majority of laboratory and morphological
recovery potential. The high prevalence of aldo-keto reductases points to markers. The activity of myofibroblasts correlated with tubular atrophy
an anti-toxic defense mechanism. (“r”= 0,53), focal sclerosis(“r”= 0,43), the stage of diabetes(“r”= 0,49)
in gr. №2 in comparison with gr. № 3. The PTC correlated with tubular
atrophy (“r”= 0,47), focal sclerosis(“r”= 0,50) and ITIN (“r”= 0,59) in
PS-10-019 gr. №2 in comparison with gr. № 3.
Clinical significance of zero-time renal transplant biopsies Conclusion: The fibrosis in tubulointerstitium of patients with DN cor-
M. Horacek1, P. Senjug2, M. Knotek3, D. Galesic Ljubanovic2,1 related with quantity of myofibroblasts and PTC. There were not
 Virchows Arch

established significant differences in fibrotic processes of the renal paren- have secondary MN associated to Psoriasis (1), HIV and lues (1) and
chyma in patients with and without NDGP. lues(1). Four patients with primary MN were negative for PLA2R in
the biopsies. Circulating anti-PLA2R antibodies were detected in 2 of
21 (9,5%) patients, both sera were sampled during active disease. Four
PS-10-022 patients with nephrotic proteinuria were negative for circulating anti-
Renal involvement in Fabry disease: a clinical, histopathological and PLA2R antibodies. All patients with negative circulating anti-PLA2R
ultrastructural study antibodies showed PLA2R antigen positive in the kidney biopsies.
G. Terinte-Balcan1, E. Rusu2, I. Gener2, M. Gherghiceanu3 In 7 of 29 patients with SLE PLA2R was positive in the kidney biopsies
1
Emergency University Hospital, Bucharest, Romania, 2 Fundeni (24,1%).
Clinical Institute, Romania, 3 Victor Babes National Institute of Conclusion: PLA2R antigen in kidney biopsies is a useful test for the
Pathology, Romania diagnosis of primary MN in the retrospective material, although our study
do not confirm previous findings of the absence of PLA2R antibodies in
Background & Objectives: Fabry disease represents a genetic disorder SLE.
in which the deficiency of the lysosomal enzyme alpha-galactosidase
leads to accumulation of glycosphingolipids. The aim of this study is to Supported by Fundação de Amparo à Pesquisa do Estado de São Paulo/
present the clinical and histological aspects of Fabry nephropathy. State of São Paulo Research Foundation, FAPESP (Proc. no2017/19352-
Methods: We conducted a retrospective study of the patients diagnosed 5 to Dr. Rosa M. Viero).
with Fabry disease at the Victor Babes National Institute of Pathology,
Ultrastructural Department between 2016 and 2019. We selected 7 cases.
2 patients were male. The average age was 47.3 years (range 30 - 61 PS-10-024
years). Glomerular filtration rates were between 49 and 123 ml/min (av- ANCA-associated glomerulonephritis in the elderly. A biopsy-proven
erage 90 ml/min). All cases presented with proteinuria (range 0.1 – 0.8 retrospective study
mg/dl), except for one female patient. One male patient had M. Wagrowska-Danilewicz1, O. Stasikowska-Kanicka2, M. Bonczysta3,
microhematuria. M. Danilewicz3
1
All patients underwent a kidney biopsy. The accumulation of lysosomes Nephropathology Department, Medical University of Lodz,
was quantified on semi-thin sections using the score developed by the Poland, 2 Department of Nephropathology, Medical University of
International Study Group of Fabry Nephropathy. Lodz, Poland, 3 Pathology Department, Medical University of
Results: The average number of glomeruli was 6.14 (range 3 – 8). 2 Lodz, Poland
of the cases presented with segmental sclerosis and other 2 with
global sclerosis. The average value of lysosome accumulation in Background & Objectives: Aging has been highlighted as a global
the podocytes was 1.5 (range 0.4 – 2.6). All cases presented with public health problem. The number of patients with kidney diseases in
inclusions in the parietal cells of the Bowman capsule. All patients the population increases as well. Antineutrophil cytoplasmic antibody –
had inclusions in the distal convoluted tube and in the tunica media, associated glomerulonephritis (ANCA -GN) is primarily a disease of the
except for one case. elderly. The aim of the study was to compare the clinical, laboratory data
Conclusion: In order to asses the prognosis of patients with Fabry dis- and microscopic lesions in the renal biopsy in ANCA-associated glomer-
ease, it is important to accurately quantify the renal involvement. In our ulonephritis in the adult patients ≤ 64 years (Group I) and in patients ≥65
series, the extent of inclusions in the epithelial cells correlated with re- years (Group II).
duced glomerular filtration rates. Methods: From January 2009 till January 2019 ANCA-associated glo-
merulonephritis were diagnosed in 32 patients ≤ 64 years, and in 53
patients ≥65 years. Baseline data including sex, age, ANCA serotype,
PS-10-023 eGFR, serum creatinine, proteinuria, and hematuria were obtained.
Autoantibodies against Phospholipase A2 Receptor in Brazilian pa- Diagnosis was based on examination of biopsy tissue with histological
tients: an overview through idiopathic membranous nephropathy confirmation of pauci -immune necrotizing glomerulonephritis together
and class V lupus nephritis with a possitive ANCA titer. Microscopic lesions were scored according
D.C. dos Santos1, C.J. Figueira1, P.F. dos Reis2, V.d.S. Silva2, R. Bruder3, to the histopathological classification for ANCA-associated
R.M. Viero1 glomerulonephritis.
1
Department of Pathology, Botucatu Medical School, São Paulo State Results: Most patients were MPO-ANCA positive. PR-3 ANCA patients
University (UNESP),Botucatu, Brazil, 2 Department of Internal were younger than MPO ANCA patients. All patients had severe kidney
Medicine, Botucatu Medical School, São Paulo State University disease (median creatinine 6 mg/dL, 35% needed temporary dialysis).
(UNESP),Botucatu, Brazil, 3 Clinical Laboratory, Botucatu Medical The sclerotic histological class was observed in the 12% of the patients
School, São Paulo State University (UNESP),Botucatu, Brazil with MPO-ANCA, as compared to 3% with PR3-ANCA. In crescentic
class of ANCA-GN the value of e-GFR and serum creatinine levels sig-
Background & Objectives: Detection of M-Type Phospholipase A2 nificantly differed as compared with other histological classes of ANCA-
antigen (PLA2R) in the kidney biopsies is a sensitive test for the diagnosis associated GN.
of primary membranous nephropathy (MN). The studies have been Conclusion: In conclusion, our study revealed no significant differences
shown that secondary forms of MN are PLA2R negative. We evaluated in baseline characteristics between both studied groups except of the
the prevalence and clinical significance of PLA2R in MN and class V higher frequency of MPO-ANCA serotype and the sclerotic histological
lupus nephritis (SLE). class of ANCA-GN in patients ≥65 years.
Methods: We reviewed the records of 71 patients of MN and 29
patients with SLE over a 12-year period. PLA2R antigen in all kidney This work was supported by grant of Medical University of Lodz 503/6-
biopsies were analysed by immunohistochemistry using rabbit poly- 038/01/503-001
clonal PLA2R1 antibody (Novus Biologicals), and circulating
PLA2R antibody in 21 serum samples of aleatory patients by
ELISA (Euroimmun). Monday, 9 September 2019, 09:30 - 10:30, Agora 3
Results: In 65 of 71 (91,5%) patients with MN, PLA2R was detected in a PS-11 | Neuropathology
granular pattern in the glomerular capillary walls. Three of 65 patients
Virchows Arch

PS-11-001 cytochrome c oxidase IV reaction and complementary techniques

Gliosarcoma: a single etiopathogenic mechanism behind this rare of electron microscopy on resin-embedded tissue.
tumour? Results: We confirmed 14 MM cases, youngest aged 9 months, by iden-
C. Alborch1, D.A. Vargas-Galván1, X. Ara-Mancebo1, E.M. Fuentes- tification of diagnostic “ragged red”/”ragged blue” fibers, lacking cyto-
Camps1, S. Ramón y Cajal Agüeras1, E. Martínez Sáez1 chrome c oxidase activity. Ultrastructurally we noticed an increase in
1
Vall d'Hebron University Hospital, Spain number and size of the mitochondria, subsarcolemmal/perinuclear accu-
mulation of abnormal mitochondria, with concentric and circular cristae.
Background & Objectives: Gliosarcoma (GS) is a rare type of IDH- In 6 cases other diagnoses were established: Becker muscular dystrophy,
wildtype glioblastoma (GB) (2%). It mainly affects adult males (40-60 Pompe disease, core disease and a desminopathy with secondary mito-
yo), and is usually supratentorial and peripherally located. Histologically, chondrial dysfunction.
the GS is characterised by a biphasic tissue pattern with alternating areas Conclusion: The morphological aspects enabled us to establish the diag-
displaying glial and mesenchymal differentiation. The most accepted nosis with major impact on clinical management and directed further
etiopathogenic mechanism is a monoclonal origin of both components with confirmatory genetic testing.
phenotypic dedifferentiation because of common molecular alterations.
Methods: Glioblastoma patients diagnosed at the HUVH Pathology de-
partment from 1999 to 2017 were identified (603 cases), selecting those PS-11-004
with GS histology. Clinicopathological data were collected. The benefits of apparent diffusion coefficient maps for high-grade
Immunohistochemical study for psMAD2, H3G34R, SOX2, IDH1, glioma delineation
p53, ATRX, GFAP and CD34 was performed. M. Hendrych 1 , H. Valeková 2 , R. Jancalek 2 , B. Musilová 3 , M.
Results: In our series, GS represent 1,9% of GB (12/603), with a striking Hermanová1
1
male predominance (10/12 cases) and a middle age of 61 yo at diagnosis. 1st Department of Pathology, St. Anne's Hospital and Faculty of
Histologically the tumour showed a biphasic pattern: glial and mesenchy- Medicine, Masaryk University Brno, Czech Republic, 2 Department of
mal, with epithelioid phenotype in the glial component in 3/12 cases. The Neurosurgery, St. Anne's Hospital and Faculty of Medicine, Masaryk
mesenchymal component had a muscular differentiation in 6/12 cases, University Brno, Czech Republic, 3 Department of Neurosurgery,
chondroid in 1/12 and solitary fibrous tumour-like phenotype in 1/12. All Faculty of Medicine, Masaryk University Brno, Czech Republic
cases were IDH, ATRX and H3G34R wildtype. p53 overexpression was
seen in 46% of cases. pSmad2 and SOX2 showed intense and diffuse Background & Objectives: Apparent diffusion coefficient (ADC) maps
positivity in 25% of cases and their expression was patchy and heteroge- provide voxel-based measures of the mean water diffusivity. As increased
neous in 75%. cellularity leads to restriction of water molecule diffusion, ADC maps can
Conclusion: Our GS series has demographic and morphological fea- have better ability to describe and delineate gliomas rather than a struc-
tures similar to the reported ones for GS. We found different patterns tural MRI. The aim of our project was to determine whether the histolog-
of expression of epithelial-mesenchymal transition (pSmad2) and ical features and boundary of high-grade gliomas (HGG) might be pre-
neural stem cell (SOX2) markers. These data would support tumour’s dicted on the basis of ADC values.
pathogenesis heterogeneity that could lead to different behaviours Methods: Our cohort comprised 24 patients with HGG in which targeted
and therapies. biopsy based on conventional MRI were performed. Tumour tissue sam-
ples were collected separately from following regions: T1WI+, T2WI+,
and regions of surgical approach T1WI-T2WI-. The samples underwent
PS-11-003 histopathological analysis for nestin, proliferation index Ki-67, and vas-
The role of skeletal muscle biopsy in the diagnostic algorithm of cular density by expression of endothelial antigen CD31. The results of
mitochondrial myopathies in children and adults - a retrospective histopathological analysis were related to the corresponding findings on
study of the histopathological aspects MRI, and the respective ADC was subtracted for each sample. The sam-
D. Costache1, A. Vrâncianu1, M. Niculae1, E. Manole2,3, A. Bastian1,4 ples were stratified by expression of nestin into a tumour core,
1
Pathology Department, Colentina University Clinical Hospital, peritumoural brain zone (PBZ = HGG infiltrating zone) and tumour-
Bucharest, Romania, 2 Research Center Colentina University free brain zone.
Clinical Hospital, Bucharest, Romania, 3 Molecular Biology Results: We demonstrated a statistically significant (p< 0.05) relationship
Laboratory, "Victor Babeș" National Institute of Pathology, between the ADC value and the histological features of HGG. Increasing
Bucharest, Romania, 4 Carol Davila University of Medicine and ADC in the vicinity of HGG was linked with decreasing cellularity, pro-
Pharmacy, Romania liferation index Ki67 and vascular density. We have also shown statisti-
cally significant difference (p< 0.05) of the ADC values for the PBZ and
Background & Objectives: Mitochondrial myopathies (MM) comprise the brain tissue with no histological sign of tumour infiltration. On the
a clinically and genetically heterogeneous group of neuromuscular disor- contrary, the characteristics based on the MRI regions were overlapping
ders, frequently multisystemic, in which the precise diagnosis is a real (p> 0.05).
challenge. MM are due to defective oxidative phosphorylation caused by Conclusion: Reported findings suggest that the ADC value might be supe-
different pathogenic mtDNA and nuclear DNA mutations. Patients may rior in specifying the boundary of histological infiltration of HGG to struc-
present their first signs and symptoms at any age, but clinical and/or tural MRI. ADC imaging could be used for more accurate planning of
morphological evidence of myopathy is not always present. The purpose surgical resection and radiation therapy in patients with diagnosis of HGG.
of this study is to highlight the usefulness of muscle biopsies in the work-
up of MM. This study was supported by the Grant Agency of Masaryk University:
Methods: We conducted a retrospective study on 41 clinically MUNI/A/1252/2017 and MUNI/A/1562/2018.
suspected cases of MM from a total number of 586 muscle biopsies
performed between 2014-2018, using the Colentina University
Clinical Hospital Pathology Department database. The skeletal mus- PS-11-005
cle tissue was obtained by open biopsy technique; muscle cryosec- Effect of stress in nasal septum surgery on the formation of dark
tions were processed using histological, histochemical, enzyme his- neurons in the hippocampus in rat
tochemical techniques, of which the most relevant for MM diagno- I. Kastyro1, M. Kostyaeva1, V. Torshin1, N. Ermakova1, G. Khamidulin1,
sis were modified trichrome Gomori, succinate dehydrogenase, Y. Guschina1, A. Kavalenko1, P. Pryanikov2
 Virchows Arch

1
Peoples' Friendship University of Russia (RUDN University), Russia, for RFGNT. Somatic variants were detected in cancer tissue of PGNT
2
Pirogov Russian National Research Medical University (RNRMU), (n=15) and RFGNT (n=15), however the variants were also seen in normal
Russia adjacent tissue in both cases (n=14 and 16, respectively). In addition, the
variants were classified as polymorphisms, not protein-affecting or likely
Background & Objectives: Background. Surgical interventions in the neutral for oncogenesis according to Cancer Genome Interpreter.
craniofascial area are a strong stress factor due to its particular sensitivity, Conclusion: These data suggest that the tumourigenesis of these rare
especially in the nasal septum. In this regard, the issue remains high- rosette-forming glioneural tumours and papillary glioneuronal tumour is
quality anesthesia. not driven by mutation in these 50 classic cancer related genes.
Objective. To study effect of stress after modelling septoplasty on the
formation of dark neurons (DN) in the hippocampus in rats.
Methods: The study was conducted on adult males-rats. In 1&2groups, PS-11-008
premedication with Phenazepamum was carried out. Group1: 30rats, local Identification of specific diagnostic pathological features on 131 com-
anesthesia(LA) with 2%lidocaine solution; Group2: 30 rats, LA with bined nerve and muscle biopsies in peripheral neuropathies (PN): a
2%ultracain solution, postoperative analgesia with diclofenac for 6 days. retrospective study
Group3,4 were controls, (10 animals). In groups1–3, pretrepantation brain R. Tanasa1, A. Bastian2,3, E. Manole1,4, C. Constantinescu1, V. Nica1, G.
fixation was performed; in Group4, similar fixation was not performed and Tudor1, O. Stefan1, C. Luca1, G. Grigore1
1
artifact DN were counted. We studied the number of DN in the hippocampus Colentina Clinical Hospital, Romania, 2 Pathology Department,
on toluidine blue Nissl stained brain sections on days 2,6&14 after surgery. Colentina University Clinical Hospital, Bucharest, Romania, 3 Carol
Results: In group 2, in the CA1, CA2, CA3 & DG zones, there were fewer Davila University of Medicine and Pharmacy, Romania, 4 Victor Babes
DN compared with group 1 on day 6 (p<0.001), and on day 14 in group 2, National Institute of Pathology, Romania
the number of dark neurons was comparable with group 3 in areas CA1 and
CA2 (p<0.05). In group 4, compared with group 3, the number of DN was Background & Objectives: PN are prevalent but insufficiently under-
significantly higher in all hippocampal zones(p<0.01). stood neurological disorders with very diverse etiologies. Sural nerve
Conclusion: DN quantitative changes in CA1, CA2, CA3 and DG zones biopsy, combined with muscular biopsy, integrated into the clinical his-
of the hippocampus may indicate the severity of surgical stress when tory of the patient, along with laboratory tests, especially electrophysiol-
using different anesthetic managment when simulating acute inflamma- ogy, can provide crucial information and a deeper understanding of the
tion on the nasal septum that occurs during septoplasty. pathological mechanisms underlying disease in selected cases.
Methods: We conducted a retrospective study on 131 combined sural
The publication has been prepared with the support of «RUDN nerve-gastrocnemius muscle biopsies performed and processed in
University Program 5-100». Colentina Clinical Hospital between 2014-2018, to investigate the sensi-
tivity of nerve biopsy by evaluating the main pathological features that
enabled us to identify various PN types, using histological, histochemical,
PS-11-007 enzyme histochemical techniques on cryosections, routine and special
Description and target mutation profile of rare glioneuronal tumours stains on paraffin-embedded tissue, resin semithin and ultrathin sections,
L.L. Sousa Veras1, M. Bisarro dos Reis1, M. de Medeiros Matsushita1, W. fiber teasing and morphometric analysis in all cases and electron micros-
dos Santos1, R. Manuel Reis1 copy in selected ones.
1
Barretos Cancer Hospital, Brazil Results: We identified vasculitic, inflammatory axonal and demyelinat-
ing PN, some related to connective tissue diseases, hypertrophic PN with
Background & Objectives: Rosette-forming glioneural tumours (RFGNT) onion-bulb formation, amyloid and tomaculous PN and much rarer types
and papillary glioneuronal tumour (PGNT) are rare low grade glioneuronal like mitochondrial neuromyopathy and a case of Fabry disease. In 3 cases,
neoplasms that account for < 1% of intracranial tumours. The objective of this a motor neuron disease was diagnosed. However, in many cases, a diag-
study was to describe and performed the mutation status of these tumours in nosis of demyelinating, axonal or mixed PN of variable severity could be
two cases (one rosette-forming and other papillary). highlighted, with only nonspecific additional findings.
Methods: One RFGNT and one PGNT were diagnosed at Barretos Conclusion: In the molecular era of medicine, the nerve and muscle
Cancer Hospital, Brazil. In the case of PGNT was performed immuno- biopsy remains a valuable diagnostic tool in carefully selected cases,
histochemistry for GFAP, EMA, ki67 and synaptophysin and in RFGNT providing relevant data, mainly in treatable types as vasculitic PN, in
case was performed ATRX, OLIG2, GFAP, NEU-N, MAP2, NF, amyloidosis and other PN with abnormal deposits, as well as in hereditary
synaptophysin, EMA, P53 and Ki67. DNA was isolated from formalin- PN when genetic tests are unavailable.
fixed paraffin-embedded (FFPE) tissue of tumour and normal adjacent
areas. The somatic mutations was analysed via massively parallel se-
quencing of 50 cancer driver genes (Ion AmpliSeq Cancer Hotspot PS-11-009
Panel V2 - SMARCB1, RB1, TP53, ERBB4, FBXW7, BRAF, KIT, Update of a series of 65 central nervous system "PNETs" according
GNAS, HRAS, EGFR, PDGFRA, PIK3CA, CDKN2A, ERBB2, ABL1, to the 2016 WHO classification
JAK2, KRAS, NRAS, NOTCH1, ATM, FGFR1, STK11, PTPN11, APC, A. Tauziede Espariat1
1
SMAD4, PTEN, SMO, CTNNB1, RET, IDH2, SRC, EZH2, VHL, MPL, Sainte-Anne Hospital, France
NPM1, FLT3, FGFR3, CDH1, KDR, HNF1A, MLH1, ALK, IDH1,
GNAQ, AKT1, JAK3, FGFR2, GNA11, MET, CSF1R). Torrent Suite Background & Objectives: The term primitive neuroectodermal tumour
Software and Variant Caller Plugin were used to call the variants and (PNET) of the central nervous system (CNS) has disappeared from the
Ion Reporter™Software was used to annotate variants. 2016 WHO classification. Data from recent literature shows that this
Results: The patient diagnosed with PGNT is female and 12 years old, the ancient nosology corresponds to various histomolecular entities.
case showed immuno-positivity for GFAP, synaptophysin and 1% of ki67. The goal is to update the histomolecular diagnosis of 65 CNS PNETs
The other patient with RFGNT is male and 36 years old, the case showed diagnosed between 1993 and 2016 in children, adolescents, and adults.
immuno-positivity for ATRX, OLIG2, MAP2, 7% of Ki67 and focal posi- Methods: After a central review of these tumours, immunohistochemical
tivity for synaptophysin, NF and NEU-N. The sequencing resulted in studies and molecular analyses (FISH, NGS, RNAseq) were performed.
amplicon coverage of at least 300× across the 207 amplicons of all samples Results: Seven tumours/65 could not be reclassified due to insufficient
analysed and mean deep for variant analyses were 2003 for PGNT and 1871 tissue material. Forty-seven/58 paediatric tumours (81%) were
Virchows Arch

1
reclassified: 1 AT/RT, 5 RELA fusion positive ependymomas, 21 University Hospital Morales Meseguer, Murcia, Spain, 2 Department of
C19MC-altered embryonal tumours with multilayered rosettes, 1 CNS Pathology and Laboratory Medicine, Loyola University Chicago, USA,
3
primitive Ewing sarcoma with EWSR1 fusion, 3 high grade gliomas with Faculty of Medicine, University of Murcia, Spain, 4 Faculty of Medicine,
MYCN amplification, 4 neuroepithelial high grade tumours with BCOR University of Split, Croatia, 5 Faculty of Medicine, University of
alteration, 4 cerebral metastases from medulloblastomas, 1 Thessaloniki, Greece, 6 Department of Internal Medicine, Morales
pineoblastoma, 2 immature teratomas with a primitive neuronal compo- Meseguer University Hospital, Murcia, Spain, 7 Intensive Care Unit,
nent, 1 pilomyxoid astrocytoma, and 4 IDH- and histone- wild type pae- Morales Meseguer University Hospital, Murcia, Faculty of Medicine,
diatric high grade gliomas. Catholic University of Murcia, Spain, 8 Department of Pathology, Reina
One tumour is an ETMR for which there is no more paraffin-embedded Sofía University Hospital, Murcia, Faculty of Medicine, University of
material, another ETMR is undergoing molecular confirmation. One gli- Murcia, Spain
oma, one tumour and one sarcoma are currently being characterised.
Conclusion: This study demonstrates the variety of histomolecular diagno- Background & Objectives: Standardised pathology examinations place
ses grouped within the ancient PNET terminology. The main paediatric enormous emphasis on theoretical pathology content. Consequently, medical
tumour is the embryonal tumour with multilayered rosettes, C19MC altered. students lack knowledge of practical Pathology, especially gross pathology.
This study shows that histopathological analyses, immunohistochemistry, In order to address this lack of practical skill, we initiated simulation-
and classical molecular biology allow for the reclassification of 81% of based practical pathology workshops at our Hospital in 2016. The goal
paediatric former PNETs. Methylome analyses could be useful for the of these gross dissection workshops was to approximate future medical
diagnosis of CNS neuroblastoma with FOXR2 activation and tumours doctors to diagnostic pathology procedures, enhancing the medical stu-
that remain unclassified. dent learning experience.
Part of this endeavor was to compare/contrast the utility of supplementing
these workshops with different teaching modalities.
PS-11-010 Methods: A 1-hour gross-dissection workshop was offered to International
An integrative radiological, histopathological and molecular analysis Federation of Medical Students’ Associations (IFMSA) students.
of paediatric pontine high-grade gliomas with MYCN amplification All participants were provided identical oral and written pre-
A. Tauziede Espariat1 workshop information. They were then divided into 3 test groups
1
Sainte-Anne Hospital, France and teaching was supplemented with: fixed pictures (group 1),
video (group 2) and live observation of a pathologist while
Background & Objectives: Diffuse midline glioma, H3K27M-mutant grossing (group 3).
was recently introduced in the 2016 WHO classification of CNS Subsequently, time taken for students to correctly perform gross dissec-
tumours and represents the main tumoural glial subgroup located in tion on handmade silicone tumour simulators was recorded. An OSCE
the brainstem. However, 2 rare groups of brainstem gliomas without Likert-like checklist was used to assess skills.
histone gene mutations have also been described: the MYCN-HGG Results: 12 students from 8 different countries participated in the workshop-
and the silent-subgroups. The aim of this study was to perform a based experiment. Time in performing the simulation was better for group 3
detailed clinicoradiologic and histomolecular study of MYCN-HGG (15’39”), followed by group 2 (16’50”) and group 1 (17’52”).
of the brainstem. Results from the skills assessment showed that grossing was slightly
Methods: A central radiological and pathological review with routine better for group 2 (3.7) in comparison with group 3 (3.4), with group 1
biomarkers assessment was performed. FISH analysis of MYCN and being worst rated (3.1) in this regard.
whole exome sequencing on cryopreserved tissue were also performed. Conclusion: Although the sample size of this study was small, results
Results: All 6 tumours presented as a nodular mass with annular en- reveal that live viewing of gross organ dissection is associated with
hancement on MRI. These tumours were morphologically poorly differ- shorter execution time. However, when quality of skills assessment
entiated with spindle cells. They did not express H3K27M, Lin28A, or where evaluated, viewing of a standardised video can improve per-
BCOR. No loss of H3K27me3, INI1 and BRG1 were observed. The formance versus the observation of a random surgical specimen.
immunohistochemical pattern showed no or focal expression of glial Thus, supplementation of live-viewing with video-viewing would
markers (GFAP and Olig2) and a constant expression of at least one likely have the ideal outcome for gross-pathology simulation educa-
neuronal marker. Four tumours overexpressed p53. All tumours presented tion and medical students understanding of practical day-to-day
with an amplification of MYCN and ID2 genes. FISH analysis confirmed Pathology.
the presence of a MYCN amplification in 4/6 cases.
Conclusion: To conclude, we described detailed clinicoradiologic and
immuno-morphologic features of 6 cases of pontine MYCN-HGG, there- PS-12-002
by highlighting the consistent amplification of MYCN and ID2 genes. Communication with pathology evaluated via the pathology requisi-
This diagnosis must be considered when microscopic features reveal a tion using 396,033 pathology reports
highly malignant undifferentiated tumour without loss of H3K27me3 M. Bonert1, A. Naqvi1, C. Finley1, R. Juergens2, P. Williams2, P. Major2,
trimethylation. Distinguishing this rare neoplasm from diffuse midline A. Kapoor1
1
glioma, H3K27M-mutant might allow for establishing targeted molecular McMaster University and St. Joseph's Healthcare Hamilton, Canada,
2
therapies in the future. McMaster University and Hamilton Health Sciences, Canada

Background & Objectives: Clinical information is often essential for an

Monday, 9 September 2019, 09:30 - 10:30, Agora 3 accurate pathologic assessment. We sought to retrospectively examine
PS-12 | Other Topics communication with pathology by assessing the clinical history (CH)
provided on the pathology requisition.
Methods: All in house surgical pathology cases and non-
PS-12-001 gynaecological cytopathology cases were retrieved within a region
Live-viewing and video-supplemented teaching modules improve de- for a seven year period (2011-2017). Using custom computer code,
livery of simulation-based gross pathology education the cases were anonymized, categorized into CH present or absent
E. Alcaraz-Mateos1, K.M. Mirza2, S. Molina-Valverde3, I. Turic4, M. and tabulated by year, hospital, submitting physician/surgeon (SPS),
Togkaridou5, F. Caballero-Aleman6, M.J. Párraga-Ramírez7, E. Poblet8 and assigned a tissue group (breast (BR), gastrointestinal (GI),
 Virchows Arch

gynaecological (GYN), head & neck+endocrine (HNE), lung (LUN), expected in suicidal hanging in 7.4 to 20% of cases. This study sought
miscellaneous (MISC), skin (SK), urologic (URO)) via free text to identify a pattern of limb bruising which occurs in association with
string matching. hanging in Ireland, its incidence, and factors which increase its incidence.
Results: Data could be extracted from 396,033 pathology reports. Methods: All hanging cases from the years 2005 to 2016 (n = 82) were
303,926 (77%) were categorized as clinical history present (CHP). retrospectively reviewed. Pattern of traumatic limb injury, toxicology,
263 SPSes submitted over 200 cases each (range 201-7119) and had type of suspension and location/scene of hanging were recorded.
mean/median/stdev/max/min CHP rates of 82%/93%/22%/100%/ Patients who had been in physical altercations or accidents prior to the
5%. A linear regression using the submitted volume to predict hanging were excluded.
CHP yielded a Pearson coefficient of -0.32. CHP varied minimally Results: 72% of reviewed cases had traumatic limb lesions, the majority
by year (range 75-78%). The CHP of surgicals by hospital (98%, of which occurred on the anterior lower limb and posterior upper limb.
86%, 85%, 59%) and cytologies by hospital (95%, 87%, 56%) var- The most common lesions were abrasions (56.1%) and bruises (43.9%).
ied significantly. CHP by tissue group was 95%, 92%, 88%, 87%, Lacerations were rare (3.7%). Positive toxicology was found to increase
84%, 77%, 75%, 63% for GYN, BR, HNE, SK, URO, LUN, MISC, the incidence of traumatic limb lesions (p = 0.001449). Suspension type
GI respectively. did not increase the incidence of limb injury.
Conclusion: The tissue type (a surrogate for department of origin), indi- Conclusion: The pattern of injury identified by our study is in keep-
vidual SPS, volume submitted and hospital of origin appear to influence ing with that found in the literature. However, the incidence is far
physician/surgeon-pathologist communication. CHP data allows one to higher than in previous studies. This could be due to differences in
make inferences about communication and may facilitate evidence based levels of intoxication or location of hanging or in differences in prac-
strategies to optimise information flow. tice of recording limb trauma in cases of hanging. Intoxication in-
creases the likelihood of traumatic limb injury, possibly due to alter-
ation of the agonal sequence.
PS-12-003
A method to obtain kappa values for synoptic report parameters
applied to data from 1,303 colorectal cancer resections PS-12-007
M. Bonert1 Immunohistochemical detection of pan-Tropomyosin Receptor
1
McMaster University and St. Joseph's Healthcare Hamilton, Canada Kinase (pan-TRK) expression in solid tumour specimens: inter-
laboratory and inter-reader concordance. Study in progress
Background & Objectives: In anatomical pathology, inter-rater varia- S. Stratton1, J. Feng1, T. Thorne-Nuzzo1, M. Kockx2, F. Penault-Llorca3,
tion is often assessed with kappa values. The objective of this work is to A. Stenzinger4, F. Lopez-Rios5,6, G. Viale7,8, F.A. Soares9, T. Chou10,11
1
generate kappa values from rate data via simulation. Roche Tissue Diagnostics, USA, 2 HistoGeneX Laboratories, Belgium,
3
Methods: Pathologist diagnostic rate (DR) data was obtained from syn- Centre Jean Perrin, France, 4 University Hospital Heidelberg, Germany,
5
optic reports in a cohort of 1,426 colorectal cancer resections (CRCRs) University HM Sanchinarro Hospital, Spain, 6 CIBERONC, Spain,
7
(accessioned 2012-2017) for tumour deposits present (TD+), margin pos- University of Milan, Italy, 8 European Institute of Oncology, Italy,
9
itive (M+), lymphovascular invasion (LVI+), pN0, LVI+ in pN0, LVI+ in University of Sao Paolo/D'Or Institute of Research, Brazil, 10 National
node positive. Virtual pathologists (VPs) (with the obtained DRs) Yang-Ming University, Taiwan, 11 Taipei Veterans General Hospital,
assessed a large virtual CRCR cohort to obtain kappas accurate to 0.01. Taiwan
The calculation made use of the maximal diagnostic overlap assumption
(MDOA); this assumes a high DR pathologist calls a diagnosis (e.g. LVI+ Background & Objectives: Tropomyosin receptor kinase fusions in-
) in all cases that a lower DR pathologist makes the call. The VPs gener- volving NTRK1, NTRK2 and NTRK3 occur in a diverse set of tumours
ated a table of diagnostic assessments (TDA). The TDA was then used to resulting in the constitutive expression of TRK fusion proteins. Wild-type
calculate Fleiss' kappa in the usual way. TRK protein expression in most solid tumours (non-neuroendocrine) is
Results: The DRs of 17 pathologists were available, where each pathol- generally minimal with low prevalence. The purpose of this study is to
ogist signed-out >25 specimens and the group together interpreted 1,303. determine the reproducibility of performance of the automated
The simulated (in silico) kappas were 0.82, 0.67, 0.59, 0.51, 0.43, 0.33 for VENTANA pan-TRK (EPR17341) Assay, intended for immunohisto-
pN0, TD+, M+, LVI+, LVI+ in node positive and LVI+ in pN0. The chemical detection of the C-terminal region of TRK proteins A, B and
MDOA represents a best case scenario for a given set of DRs; however, C, by assessing interpretations of individual pathologists.
the calculated (in silico) kappa values have trends similar to experimental Methods: This is an inter-laboratory reproducibility study using archived
kappas in the literature. specimens, involving 3 replicate tissue sections from each of 50 cases (25
Conclusion: The calculated (in silico) kappas are derived from the as- sequencing-confirmed NTRK fusion-positive and 25 NTRK fusion-nega-
sessment of complete cases in a practice setting; they are devoid of study tive) for evaluation at seven independent global sites. Sites are blinded to
set selection bias and other study associated confounders. The MDOA fusion status of the individual specimens, which will be divided among
may approximate diagnostic disagreement patterns in clinical practice. the sites for staining and then collated for interpretation of digital images.
The development of intuitive metrics accessible to pathologists, that can Primary endpoints will include between-site and between-reader compar-
be applied to observational data, may be important to improve care. isons of average positive agreement, average negative agreement, and
overall percent agreement.
Results: Evaluation of 50 cases (1050 observations) will provide a two-
PS-12-005 sided, 95% lower confidence bound interval of 87.2% using the Wilson
Review of the pattern of traumatic limb lesions sustained in cases of (score) method if a 90% concordance is reached. When completed, this
hanging study will verify assay performance across the 7 laboratories, help deter-
M. Mc Cabe1, N. Fyzul2, L. Mulligan3 mine robustness of the assay, and help guide training and education for
1
Cork University Hospital, Ireland, 2 University College Dublin, Ireland, pathologists. Preliminary results will be presented.
3
Office of the State Pathologist, Dublin, Ireland Conclusion: This study design provides a framework to determine
the reproducibility of the VENTANA pan-TRK (EPR17341)
Background & Objectives: Evidence of limb trauma in hanging can Assay. Additionally, the results can be used to provide a basis
raise suspicion of foul play. However, according to the literature, a pattern of determination of the presence of TRK protein overexpression
of trauma on the anterior lower limb and posterior upper limb can be using immunohistochemistry.
Virchows Arch

Monday, 9 September 2019, 09:30 - 10:30, Agora 3 positive for T790M by RC but negative by SuperARMS kit. Using the
cobas test as the reference, the overall percent agreement is 91%, kappa
PS-13 | Pulmonary Pathology
value was 0.8.
Conclusion: SuperARMS EGFR assay is highly sensitive and specific
PS-13-001 method to detect tissue and plasma EGFR mutations in lung cancer pa-
DNA methylation and long non-coding RNA in lung tients. Its performance is comparable to the cobas EGFR kit.
adenocarcinoma
S. Ahn1, J. Y. Pyo1, J. Song1, Y. J. Lee2
1
International St. Mary's Hospital, Republic of Korea, 2 Korea University PS-13-003
Anam Hospital, Republic of Korea Comparison of ddPCR and qPCR for detection of EGFR mutations
in plasma cell-free DNA in Lung Adenocarcinoma.
Background & Objectives: Exposure to cigarette smoke is powerful J. Uyboco1, M.S. Aguilera1, J.J. Andal1, V. Dy1, M.V. Cruz-Ordinario1,
environmental modifiers of aberrant DNA methylation, especially in lung R. Li1, D. Ang1
1
carcinogenesis. Thus, smoking induced molecular alteration in lung can- St. Luke's Medical Center, Philippines
cer will provide a range of exposures ideal for the study of smoking-
induced carcinogenesis. Herein, we explored the epigenetically regulated Background & Objectives: Circulating tumour DNA (ctDNA) is a
long noncoding RNA (lncRNA) and DNA methylation, associated with promising, non-invasive method for epidermal growth factor receptor
smoking in lung adenocarcinoma (LUAD). (EGFR) mutations detection in lung cancer patients. In this pilot study,
we evaluated and compared the performance of digital droplet PCR
Methods: TCGA datasets of DNA methylation and mRNA expression
(ddPCR) vs. real time PCR (qPCR) in detecting EGFR mutations in
profiles were used. LUAD samples were divided into smoker LUAD and
plasma ctDNA from patients with advanced lung adenocarcinoma. The
never-smoker LUAD. The differentially methylated regions (DMRs) and
possibility of the implementation of ddPCR platform in the detection of
the differentially expressed lncRNAs (DE-lncRNAs) were screened in
EGFR mutation in samples with low mutation rates, was assessed.
smoker LUAD vs. normal, never-smoker LUAD vs. normal, and smoker
Methods: In this study, ddPCR (BIORAD, QX200) and qPCR (Roche
LUAD vs. never smoker LUAD. Integrated analysis of DE-lncRNAs
Cobas v2) were used to analyse 39 plasma ctDNA from lung adenocar-
associated with DMRs was performed. Validation analysis was done in
cinoma patients, in detecting EGFR exon 19 deletion (E19del), exon 21
76 patients with LUAD, using bisulfite sequencing for ADAM6, AGR2,
L858R (L858R), and exon 20 T790M (T790M).
AURBK, BUB1B, CAV1, CCNB1, FOXP3, HMGA1, MMP13, and
Results: Both platforms detected EGFR E19del, L858R, and T790M,
SBSN.
in 27% (9/34), 29%(11/38), and 23% (9/39) respectively. One (3%)
Results: We identified that epigenetic regulated lncRNAs (HOTAIR, L858R, one (3%) E19del and three (8%) cases of T790M were de-
SYN2, MALAT1, H19, CYP4A22-AS1 and Lnc-MUC2-1) were sig- tected with qPCR but not by ddPCR. On the contrary, one (3%) case
nificantly differentially expressed in smoker LUAD. The most sig- of E19del and nine (23%) cases of T790M were detected by ddPCR
nificantly related category of GO analysis was LPS/IL-1 Mediated but not by qPCR. The concordance of the two platforms in detecting
Inhibition of RXR Function. In validation analysis, four CpG sites of E19del, L858R and T790M are as follows: 94% (k=0.86, 95%CI
ADAM6, AURBK, FOXP3 and HMGA1 showed borderline 0.67-1.0), 97% (k=0.94, 95%CI 0.81-1.0), and 70% (k=0.4, 95% CI
significance. 0.09-0.065), respectively.
Conclusion: Our study indicated that epigenetic regulated lncRNAs were Conclusion: This study demonstrates the feasibility of using ddPCR
significantly and differentially expressed in smoker LUAD. They may in detecting EGFR mutations in ctDNA of lung adenocarcinoma pa-
exert a significant epigenetic role in lung cancer development and could tients. It also highlights the advantage of utilizing ddPCR especially
be potential targets for future treatment of LUAD. in the detection of T790M resistance mutation, for patients with low
mutation burden, enabling early detection and appropriate clinical
management.
PS-13-002
SuperARMS EGFR mutation detection kit vs. qPCR in detecting
EGFR mutations in tumour tissue and plasma cell-free DNA of lung PS-13-004
cancer patients Ciliated muconodular papillary tumours of the lung, an increasingly
M.K. Zerna1, M.S. Aguilera1, V. Dy1, J.J. Andal1, D. Ang1 recognised entity in surgical lung resection specimen
1
St. Luke's Medical Center, Philippines K. Argyropoulos1, N. Narula1, A. Moreira1, F. Zhou1, M. Bannan1, J.
Melamed1
Background & Objectives: Filipinos with lung adenocarcinoma has a 1
New York University School of Medicine, Department of Pathology,
reported EGFR mutation rate of 49.4%. The SuperARMS EGFR muta- USA
tion detection kit has been reported to detect 41 EGFR somatic mutations,
with a sensitivity (0.2% mutant) higher than qPCR. We aim to compare Background & Objectives: Ciliated muconodular papillary tumour
SuperARMS with RocheCobasv2 (RC), which is the currently used plat- (CPMT) is a rare benign lesion, which occurs in the periphery of the lung
form in our hospital, in the detection of EGFR mutation status using both and is characterised by papillary architecture, intra-alveolar mucin and the
tissue and plasma samples. presence of non-atypical ciliated-columnar, basal and mucous cells. Since
Methods: A total of 42 lung adenocarcinoma patients (22 tissueDNA and its introduction in 2002 by Ishikawa et al, this entity counts a few reports
20 plasmaDNA) were tested using the RC and SuperARMS (AmoyDX) in the literature, which have primarily occurred in East Asia. Although
kits. Concordance rate of EGFR mutation status between the two detec- not in the 2015 WHO classification, CPMT represents a frank neoplastic
tion kits was analysed. Kappa value was calculated for concordance process, harbouring genetic alterations including BRAF and EGFR mu-
analyses. tations. The goal of this study was to characterise the clinicopathologic
Results: Of 22 lung adenocarcinoma tissue DNA samples, 12 (54%) had features of CPMT diagnosed at a tertiaty care institution in the U.S.
EGFR mutations, detected by both platforms. SuperARMS detected an Methods: Nine cases with characteristic features of classic and non-
additional S768I and a T790M mutation. Of the 19 lung adenocarcinoma classic CPMT from New York University Tisch Hospital and Bellevue
plasma DNA samples, 9 (47%) were positive for EGFR mutations in both Hospital from 2016 to 2019 were identified. Clinical and pathologic data
platforms; three cases had concurrent T790M mutations. There is one case were reviewed.
 Virchows Arch

Results: CPMTs were identified in 3 Male and 6 Female patients, were incidental findings in resections performed for a dominant lesion,
whose age ranged from 47 to 82 years old. The lesions were predom- which was either adenocarcinoma, non-mucinous type (case 2) or
inantly found in the right lung and had a median size of 6 mm. Six (6) atypical carcinoid (case 8). All lesions showed the characteristic im-
cases represented classic CPMTs, while 3 cases lacked the full spec- munohistochemical TTF-1 stain of columnar cells and p63 or p40 stain
trum of CPMT diagnostic features, and were classified as non-classic of basal cells. Two out of four (2/4) cases stained for BRAF-V600E
CPMTs. While in 7 cases, surgical resection was performed due to showed uniform staining of all 3 cellular components of the lesion.
radiologic diagnosis of a peripheral nodule, in 2 cases, small CPMTs The data are summarized on Table 1.

Table 1 Clinicopathologic features of CPMT diagnosed at tertiary care institution in 2016-2019

Case Age(y)/ Site Size (greatest Specimen Classic (C) vs Concomitant pathologies Immunophenotype
Sex dimension, Non-classic in same (s) or other
mm) (NC) (o) resection site

1 73/Male RLL 8 Wedge C No TTF-1(+) p63(+)

2 66/Female RUL 1 Segmentectomy C Multifocal non-mucinous TTF-1(+), p40(+)
adenocarcinoma (s),
Respiratory Bronchiolitis (s)
3 82/Male RLL 6 Lobectomy C Bronchiolar Metaplasia (s), TTF-1(+), p40(+)
Adenocarcinoma (o)
4 82/Female RML 2 Wedge C Neuroendocrine hyperplasia TTF-1(+), p40(+),
(s), Chronic Bronchiolitis BRAF-V600E (-)
(s), Squamous cell
carcinoma (o)
5 71/Female RLL 20 Wedge C Resolving pneumonia (s) TTF-1(+), p63(+),
BRAF-V600E (+)
6 80/Male LUL 13 Wedge NC No TTF-1(+), p40(+),
EGFR-L858R (-),
EGFR-E746_
A750del (-), ALK
(-), BRAF- V600E (-)
7 59/Female RLL 4 Wedge NC No TTF-1(+), p40(+)
8 71/Female RUL 2 Lobectomy C Atypical carcinoid (s), TTF-1(+), p40(+)
Neuroendocrine hyperplasia
(s), Atypical adenomatous
hyperplasia (s)
9 47/Female RLL 20 Lobectomy NC No

Conclusion: CPMTs although infrequent are now increasingly recog- classification (TNM8) were informed on data from large international
nized and their incidence appears higher than reported in western litera- patient cohorts. Notably, patients treated with neoadjuvant chemo-
ture. Interestingly, this self-limited tumour shares similar driver mutations therapy were excluded. We aimed at comparing TNM8 to the 7th
with lung adenocarcinoma. Further studies will include a comprehensive edition (TNM7) and regression staging in neoadjuvantly treated pa-
immunohistochemical and molecular characterization of these nine cases tients in a single-center retrospective study.
and comparison with morphologically similar non-neoplastic processes, Methods: We analysed 131 consecutive patients with NSCLC resected
like bronchiolar metaplasia. after neoadjuvant (radio)chemotherapy, 2000-2016. The pathological
slides, clinical records and CT-scans were reevaluated assessing
tumour-size according to current IASLC-recommendations, TNM7,
PS-13-005 TNM8, histological and radiological regression.
Prognostic value of the 7th and 8th edition of the TNM classification The cohort consisted of 59 squamous cell carcinomas, 65 adenocarci-
and pathologic and radiologic regression in non-small cell lung can- nomas and 7 others. Applying TNM8 staging criteria led to down-
cer resected after neoadjuvant treatment staging 2/131 (1.5%) and an up-staging 32/131 (24.4%) patients.
C. Bello1, P. Zens2, A. Scherz3, J. Koenigsdorf4, A. Pöllinger5, R.A. Median progression free survival (PFS) was 13 months (95%CI=4.3-
Schmid6, A. Ochsenbein7, I. Zlobec2, C. Neppl2, S. Berezwoska2 70.5 months). Median overall survival (OS) was 16 months
1
Institute of Pathology, University of Bern, Switzerland, 2 Institute of (95%CI=4.1-88.5 months).
Pathology, University of Bern, Switzerland, 3 Department of Medical Results: Higher stage as assessed by both TNM8 and TNM7 was signif-
Oncology Inselspital, University Hospital Bern, Switzerland, icantly associated with shorter PFS (p=0.002, p<0.001), but only apply-
4
Department of Diagnostic, Interventional and Paediatric Radiology, ing TNM8 with shorter OS (p=0.002; p=0.439). Pathological regression
University Hospital Bern, Switzerland, 5 Department of Diagnostic, grading alone (<1%, <10% or ≥50% viable tumour cells) was associated
Interventional and Paediatric Radiology, Inselspital University Hospital with PFS (p=0.037), even stronger if combined into a score including ypT
Bern, Switzerland, 6 Department of Thoracic Surgery, Inselspital and ypN (p=0.005), but not OS. There was no correlation between CT-
University Hospital Bern, Switzerland, 7 Department of Medical assessed and pathological tumour size. Radiological regression using
Oncology, Inselspital University Hospital Bern, Switzerland RECIST criteria alone lacked significant association with OS or PFS.
Conclusion: In conclusion, we document a prognostic value of the
Background & Objectives: Adaptations for non-small cell lung can- TNM8 staging system and histopathological regression grading in
cer (NSCLC) in the 8 t h edition of the UICC/AJCC TNM NSCLC patients treated with neoadjuvant (radio)chemotherapy.
Virchows Arch

PS-13-006 with clinicopathological data and survival in 98 cases of human lung

PD-L1 expression in 1051 non-small-cell lung cancer samples of a adenocarcinoma patients.
tertiary hospital in 2017-2018 and concordance in paired samples Results: Higher OCT4 expression was related to improved 5-year
L. Blasco Santana1, S. Hernández-Bonilla1, A. Rodríguez Garcia1, R.M. overall survival (OS) (p<0,001).Patients with N2 disease were
Regojo-Zapata 1 , R. Rosas 2 , C. Rodríguez-Antolín 3 , I. Esteban- found to have lower LIN28A expression compared to patients
Rodríguez1,2 with N0 and N1 disease (p<0,01).Nuclear LIN28B expression
1
Pathology Department, La Paz University Hospital, Madrid, Spain, was lower in stage I and II tumours (p<0,05).LIN28B cytoplasmic
2
Biomarkers and Experimental Therapeutics in Cancer, IdiPAZ, expression was associated with 5-year OS not only in univariate
Madrid, Spain, 3 Cancer Epigenetics Laboratory, INGEMM, La Paz (p<0,005),but also in multivariate analysis (age, gender, histolog-
University Hospital, Madrid, Spain ical subtype and stage were used as cofactors, p<0,01
HR=2.592).In particular, patients with lower expression showed
Background & Objectives: Programmed Death Ligand 1 (PD-L1) is an improved 5-year OS.
important biomarker in lung cancer. Our objective is to describe our Conclusion: The results suggest that OCT4 and in particular LIN28B are
findings in non-small-cell lung cancer (NSCLC) patients in 2017-2018 promising prognostic biomarkers and could serve as future therapeutic
in our centre and analyse concordance between paired samples (cytology, targets in lung adenocarcinoma.
diagnostic biopsy and surgical piece).
Methods: We retrieved PD-L1 expression (%) and histological subtype
from 1051 cases of NSCLC diagnosed in 2017-2018 in our centre. 621 PS-13-008
samples (59.1%) were external consult cases. Our cases (430) were 206 EGFR mutations in Fez population: about 69 patients
diagnostic biopsies, 154 surgical pieces and 70 cytology specimens (50 S. Boukansa1, S. El Bardai2, Z. Benbrahim3, N. Mellas3, H. El Fatemi4,5
1
cell block and 20 liquid cytology samples). Fifteen surgical pieces were Medical Centre of Biomedical and Translational Research, Faculty of
paired with biopsy (12) or cytology (3), and 12 diagnostic biopsies with Medicine and Pharmacy Fez, Morocco, 2 Anatomy and Cyto-
cytology. pathological Department, CHU HASSAN II Fez, University Sidi
Results: PD-L1 was evaluable in 993 cases (94.5%). PD-L1 ex- Mohamed Ben Abdellah, Morocco, 3 Department of Oncology, CHU
pression was negative [<1%] in 378 cases (37.9%), it had low HASSAN II Fez, University Sidi Mohamed Ben Abdellah,
expression [1-49%] in 330 patients (33.1%), and high expression Morocco, 4 Department of Pathology, Hassan II University Hospital,
[≥50%] in 289 cases (29.0%). We found a higher proportion of Fez, Morocco, 5 Faculty of Medicine and Pharmacy of Fez, Morocco
PD-L1≥1% in squamous cell carcinoma (68.8%) than in adeno-
carcinoma (57.8%). Biopsy-surgical piece concordance was poor Background & Objectives: EGFR mutations in NSCLC, dysregulate
with Kappa=0.28 and an Intraclass Correlation Coefficient (ICC) various oncogenic mechanisms, including proliferation, increased malig-
of 0.04, while cytology-biopsy concordance was moderate with nant cell survival, invasion and metastasis. The management of NSCLC
Kappa=0.50 and ICC=0.60. Epidermal Growth Factor Receptor has envolved with the use of driver mutation in tumours samples toward
(EGFR) mutations were associated with a lower level of PD-L1 selecting the right agent for a patients treatement. EGFR mutations is a
expression, as 15 (68.2%) EGFR mutated cases were PD-L1 neg- predictive marker of tumour response to EGFR tyrosine kinase inhibitor
ative (P=0.005). treatment. The aim of this prospective study is to define the frequency and
Conclusion: Our PD-L1 expression prevalence is similar to that de- predictive value of EGFR mutations in Fez population with NSCLC.
scribed in current literature. Despite having only a few paired cases, we Methods: 69 formalin-fixed paraffin-embedded tumours from patients
believe that poor to moderate concordance is caused by tumour hetero- diagnosed with NSCLC were included. The presence of EGFR mutations
geneity and not by the type of sample chosen. Besides, EGFR mutations was determined by three methods according to percentage of tumour
may affect PD-L1 expression profile. cells. For tumours with high percentage of tumour cells> 30%, PCR
amplification followed by automatic direct sequencing was performed.
The therascreen EGFR RGQ PCR Kit which is designed to detect the
PS-13-007 most commonly reported EGFR 29 mutations, was performed in samples
Expression of pluripotency factors Oct4 and LIN28 in lung with tumour cells< 30%. All mutations obtained by QPCR were
adenocarcinoma comfirmed by Pyrosequencing.
P. Bosgana1, F. Dimitrakopoulos2, F. Sampsonas3, H. Kalofonos4, V. Results: 17 mutations were detected in the serie of 69, more frequently in
Zolota5 womens(52.9%) and non smokers(70.5%). The main types were in-frame
1
Department of Pathology, University Hospital of Patras, Greece, deletions in exon19 (58.8 %), followed by the missense substitution in
2
Department of Oncology, University Hospital of Patras., Greece, exon21 (23.5%), three patients had exon20 mutations (17.6%). 8patients
3
Department of Respiratory Medicine, University Hospital of were excluded due to lost to follow-up or death. 7patients demonstrated a
Patras, Greece, 4 Department of Oncology, Medical School, marked response to afatinib with stable disease. One patient devellop a
University of Patras, Greece, 5 Department of Pathology, resistance after 12 month on afatinib therapy, a T790M mutation is
Medical School, University of Patras, Greece thought to cause this resistance.
Conclusion: Consistent with what has been reported in other studies,
Background & Objectives: Lung adenocarcinoma is a leading cause EGFR mutations were more common in womens, non smokers and lung
of cancer mortality worldwide despite recent therapeutic advances. adenocarcima histology. This preliminary results of EGFR mutations in
Cancer stem cells (CSCs) have gained an increasing attention, due Fez population reveals an overall prevalence of 24.6%, wich is somewhat
to their ability to generate new tumour through their self-renewal higher than north america (22%), higher than Europe (15%), but lower
potential and differentiation into multiple cell lineages.OCT4 and than Asia Pacific (47%).
LIN28 (homolog A and B) have been identified as key regulators
of pluripotency in mammalian embryonic and induced stem cells
and are proven to be crucial for cancer development, but our PS-13-009
knowledge concerning their exact role in lung adenocarcinoma is Optimal diagnostic algorithm for morphological diagnosis and man-
limited. agement of patients with NSCLC lung tumours: 4 years experience of
Methods: The present study investigates the immunohistochemical ex- one center
pression of pluripotency factors (OCT4, LIN28A, B) and their association M. Byakhova1, L. Gurevich2, V. Ashevskaya1, V. Byakhova3
 Virchows Arch

1
M.F. Vladimirskiy Moscow Region Research Clinical Institute, PS-13-011
Moscow, Russia, 2 The State Budgetary Healthcare Institution of The optimal use of image analysis in the assessment of PD-L1 immu-
Moscow Area Moscows regional research clinical Institute n.a. M.F. nostaining in non-small cell lung cancer
Vladimirskiy, Moscow, Russia, 3 Peoples' Friendship University of J. Fay1, A. O'Grady1, K. Sheehan1, M. Redmond2, B. Doyle1
1
Russia (RUDN University), Moscow, Russia Department of Pathology, Royal College of Surgeons in Ireland,
Beaumont Hospital, Dublin, Ireland, 2 Department of Histopathology,
Background & Objectives: At present, it is necessary to divide lung Beaumont Hospital, Dublin, Ireland
cancer (LC) before surgery not only into variants, but also to determine
their histological and molecular subtype, as this significantly changes the Background & Objectives: The immunohistochemical analysis of PD-
prognosis of the course of the disease and the management tactics of a L1 in non-small cell lung cancer (NSCLC) is an important diagnostic test
treatment patient. The aim of our study was to determine the histogenesis, to assess the potential response of the tumour to immunotherapy. The
immunophenotypic and genetic characteristics of the neoplasm for the assignment of PD-L1 staining into categories (<1% tumour proportion
development of optimal therapeutic approaches in each case. score (TPS), 1-49% TPS and ≥50% TPS) is the current benchmark for
Methods: Since January 2014 to July 2018 morphological and immuno- treatment decisions, with only those with ≥50% TPS eligible for first-line
histochemical (IHC) and genetic research of 326 samples of lung tumours immunotherapy treatment in Ireland.
was carried out. For IHC studies a panel of markers was used: The aim of this study was to assess if image analysis of PD-L1 immunostaining
cytokeratins (CK) 7, 5/6, TTF-1, napsin A, p63). Also determined muta- alone or alongside immune cell markers correlated with manual interpretation.
tions in the genes EGFR. Methods: We compared the TPS as assessed by two pathologists to the
Results: In 148 cases, the diagnosis was made on hematoxylin/eosin- positive percentage score using QuPath software in 20 NSCLC cases.
coloured glasses (highly and moderately differentiated cases of adenocar- Results: When using image analysis to measure the level of positive
cinomas (AK) (72cfse) and squamous cell carcinoma (SCC) (73case)). membrane staining alone only 5/20 (25%) cases were in agreement.
With poorly differentiated tumours, a panel of 3 markers (CK7, TTF-1, However when a minimum nuclear size was added in an attempt to
Napsin A) was placed at the first stage. It made possible to differentiate eliminate non-tumour cells 13/20 (65%) cases were in agreement. The
AK. 25 patients (31%) with abnormalities in the EGFR gene were pre- addition of CD4 and CD68 immunostaining to the analysis to help elim-
scribed targeted therapy. The second stage delivered markers p63 and inate PD-L1 positive immune cells did not improve the number of cases
CK5/6 to confirm cases of SCC, they went to polychemotherapy and in agreement. The analysis of cases close to the ≥50% TPS score (40-
radiation. 60%) using PD-L1 positive membrane staining and nuclear size showed
Conclusion: Accurate morphological diagnosis plays a key role in choos- that 6/8 (75%) cases were in agreement.
ing the optimal treatment strategy and determining the prognosis for Conclusion: Image analysis may be a useful tool to support the pathol-
patients with various lung tumours. ogist in assessing PD-L1 TPS in NSCLC, especially for cases close to the
≥50% threshold for treatment

PS-13-010
Aquaporin-3 expression profile in malignant mesothelioma PS-13-012
S. Carnevale1, G. Ferrario2, U. Laforenza3, P. Morbini1 Bronchial-pulmonary carcinomas actin and fibroelastotic stroma:
1
Section of Anatomical Pathology, Department of Molecular Medicine, suggestion for routine report
University of Pavia, Italy, 2 PhD in Experimental Medicine, Department J. Fraga1, V. Sousa1,2, L. Carvalho1,2
of Molecular Medicine, University of Pavia, Italy, 3 Department of 1
Centro Hospitalar e Universitário de Coimbra, Portugal, 2 Faculdade de
Physiology, University of Pavia, Italy Medicina da Universidade de Coimbra, Portugal

Background & Objectives: Aquaporins regulate water transport in Background & Objectives: American Thoracic Society/European
normal and neoplastic cells. They also play a role in cell migration, Respiratory Society (ATS/ERS) defined in 2013 Idiopathic
proliferation and adhesion. Preliminary data have shown AQP-1 Pleuroparenchymal Fibroelastosis as «rare condition that consists of fi-
upregulation in MM, but other aquaporin such as AQP-3 could brosis involving the pleura and subpleural lung parenchyma, predomi-
present disregulation and be used as potential therapeutic targets: nantly in the upper lobes, with elastotic fibrosis, intraalveolar fibrosis and
AQP-3 (an aquaglyceroporin expressed in the stratum corneum of commonly associated to recurrent infections».
the skin) was found to be overexpressed in colorectal, cervical, Methods: This disease may not be rare but its characteristics may help to
lung, oesophageal, gastric, skin and tongue (squamous) carcinomas understand tumoural stroma as an important element for targeted therapy
and in hepatocarcinomas. as epithelial malignant cells. Then tumoural stroma demands reporting/
Methods: Supported by preliminary biochemical results, a consecu- scoring containing either its quality or relative percentage. Currently,
tive series of ten MM samples was evaluated with immunohisto- bronchial-pulmonary carcinoma presents four main patterns concerning
chemistry (Sigma Aldrich anti-AQP3 antibody) and AQP-3 expres- lymphoid, fibrolymphocytic, predominantly fusiform celled stroma-with
sion was compared with adjacent non-neoplastic mesothelium. We smooth α-actin/elastin deposition, and bronchioloalveolar pattern, vali-
evaluated only the positivity or negativity, regardless of the intensity dated by immunohistochemistry/histochemistry for α-actin and elastin,
of the staining. respectively.
Results: Expression of AQP-3 was observed in 7 out of 10 cases, with a Results: Searching for smooth α-actin/elastotic fibers in pulmonary
membrane (62%) or cytoplasmic (25%) pattern of expression in up to diseases, also raises understanding of a new repair cascade in chronic
70% of MM cells, while expression in non-neoplastic mesothelium was collagenizing pleuritis, young men non-smokers/smokers spontane-
not significant. The only case of sarcomatoid malignant mesothelioma in ous pneumothorax with sub-pleural triangular infancy infarcts scars
our series was found to be negative for AQP-3. and in peripheral adenocarcinomas stroma, under two delineated pat-
Conclusion: AQP-3 appears to be upregulated in 70% of our series of terns: basal membrane type and/or well defined elastotic stroma, with
MMs, with a prevalent expression on the membrane surface, where the variable smooth α-actin positivity - emphasized in surgical speci-
protein can play its natural role in water (and glycerol) exchange. The mens, where stromal heterogeneity commits with malignant epitheli-
cases where a cytoplasmatic pattern was observed, suggest us that protein al heterogeneity.
can play a pathogenetic role not only if correctly exported to the cellular Conclusion: Pancreatic ductal adenocarcinoma prognosis is an example
membrane, but also if accumulated in the cytoplasm. of α-SMA mRNA expressed by activated stromal regulating malignant
Virchows Arch

behaviour of pancreatic cancer cells; high density of stromal Background & Objectives: Carboxyl terminus of Hsp70-interacting
myofibroblasts identified with α-smooth muscle actin may contribute to protein (CHIP) is a negative regulator of necroptosis via inhibition of
poor survival in patients with solid cancers (Sinn 2014/ Fujita 2010/Liu Receptor-interacting serine/threonine-protein kinase 3 (RIPK3).
2016/Nishishita 2018). Fibroelastotic stroma stands without clinical com- Necroptosis, a form of caspase-independent programmed cell death, pro-
mitment and it might be related with better prognosis, demanding search motes cancer progression and metastasis in a few cancer types although
in either tumoural/non-tumoural pulmonary disease. anti-tumour effects of necroptosis have been reported. However, the clin-
icopathologic role of CHIP expression in non-small cell lung cancer
(NSCLC) is still poorly characterised. Herein, we aimed to evaluate the
PS-13-013 prognostic implication of CHIP expression in NSCLC.
A standardised structured training of pathologists to improve inter- Methods: Immunohistochemistry (IHC) for CHIP was performed on
and intra-reader reproducibility for scoring PD-L1 expression levels tissue microarray in 404 NSCLC patients. The cytoplasmic expression
in non-small cell lung cancer: results of a worldwide training was assessed by semi-quantitative H-score (range 0-300) using image
programme analyser. CHIP was subdivided into positive and negative using optimal
B. Jasani1, R. Oberthür1, G. Bänfer1, R. Diezko1, G. Kumar1, J. cut-off point (score 242) and was correlated with clinicopathologic
Rüschoff1, H. Schildhaus2 features.
1
Targos Molecular Pathology GmbH, Germany, 2 University of Essen, Results: Eighty-nine patients (22.2%) showed high expression for CHIP
Germany by IHC. High CHIP expression was associated with squamous histology
(p < 0.001) and the lower stage (p = 0.010), but other parameters includ-
Background & Objectives: Immunohistochemical diagnostic testing for ing smoking (p = 0.178), tumour size (p = 0.120) and adjuvant treatment
programmed cell death-ligand 1 (PD-L1) has been approved for targeted (p = 0.280) were not statistically significant. In univariate analysis, high
treatment of several major cancer types including non-small cell lung CHIP expression was associated with the longer overall survival (OS)
cancer, NSCLC. However, the semi-quantitative scoring of PD-L1 ex- (log-rank test, p = 0.044). In multivariate analysis, high CHIP expression
pression is complex and requires training of pathologists to reduce inter- was an independent favourable prognostic factor for OS [HR 0.477, (95%
and intra-reader variability. Here we present our data for a worldwide, CI, 0.235-0.966), p = 0.040], but not disease-free survival (log-rank, p =
expert-led training in PD-L1 interpretation and scoring of NSCLC cases, 0.321).
conducted over a two-year period, 2016-2017, using glass slides or equiv- Conclusion: High CHIP expression is an independent favourable prog-
alent digital images nostic factor in NSCLC, suggesting the potential role of CHIP as the
Methods: Tissue slides representative of NSCLC resected specimens novel therapeutic target for NSCLC.
with differing PD-L1 expression levels enriched around the relevant clin-
ical cut-offs, were stained with the PD-L1 IHC pharmDx 22C3 assay.
After initial training and a self-assessment exercise, the participants PS-13-015
(n=751) were given 20 cases on Day 1, followed by a further 25 cases The prognostic significance of lung adenocarcinoma grading
on Day 2, including 15 slides already seen on Day 1. From the data P. Kisialeu1
1
obtained, inter-reader overall percentage agreement (OPA), and the N.N. Alexandrov National Cancer Centre of Belarus, Belarus
intra-reader OPA were calculated.
Results: The inter-reader OPA for PD-L1-stained NSCLC were calculat- Background & Objectives: WHO 4th classification of lung tumours
ed to be 95.6% (Cohen kappa, CK = 0.84) for TPS ≥1%, and 87.3% (CK introduced the changes concerning the histological assessment of lung
= 0.74) for TPS ≥50% cut-off, respectively. The corresponding intra- adenocarcinoma and it’s grading in particular. The aim of the research
reader OPA were calculated to be 95.9% (CK = 0.87) and 91.4% (CK = was to establish the predictive value of new histological features in com-
0.83) for the ≥1% and ≥50% cut-offs. parison with the previous classification system.
Conclusion: The consistently high inter- and intra-reader agreements Methods: We investigated the clinical, histological and follow-up data of
observed are promising, given: a) the complexity of scoring tumour cells the retrospective group of 100 patients (64 males, 36 females, mean age
especially with heterogeneous PD-L1 staining pattern; b) the varied back- 64,6 years old) with primary lung adenocarcinoma. The group included
ground in terms of expertise and experience of the participants; and c) the 47% of cases with the clinical stage I, 23% – stage III, 21% – stage II and
use of digital images in addition to glass slides to manage the worldwide 9% – stage IV. All the patients underwent treatment in the N.N.
training programme. Alexandrov National Cancer Center of Belarus in 2012.
Background Biotechnological Support from Dako/Agilent & MSD. Results: Depending on the predominant histology subtype of the tumour,
all cases have been classified as three grades: G1– lepidic and minimal
invasive carcinoma (19%), G2 – acinar (39%) and papillary (9%) carci-
PS-13-014 noma, G3 – solid (19%), micropapillary (8%) and invasive mucinous
High expression of Carboxyl terminus of Hsp70-interacting protein (6%) carcinoma. The statistical analysis showed the significant difference
(CHIP) is a favourable prognostic factor in Non-small cell lung in 5-year survival between G1, G2 and G3 groups (100,0% vs 61,9% vs
cancer 8,0%, Kaplan-Meier, p<0.001). Unfavourable prognostic value of such
J. Kim1, J. Chung2, Y.S. Park1, S.J. Jang1, C.M. Choi3, H.R. Kim4, J.S. factors as the presence of foci of necrosis (p<0.001) and desmoplasia
Song5 (p=0.02) in the tumour tissue were established.
1
Department of Pathology, University of Ulsan College of Medicine, Conclusion: The study confirms that the new principles of diagnosis and
Asan Medical Center, Seoul, Republic of Korea, 2 Experimental grading of lung adenocarcinoma described in the WHO classification
Pathology Laboratory, Laboratory of Pathology, Center for Cancer have a high prognostic value.
Research, National Cancer Institute, National Institutes of Health,
Bethesda, Maryland, USA, 3 Department of Internal Medicine,
University of Ulsan College of Medicine, Asan Medical Center, Seoul, PS-13-016
Republic of Korea, 4 Department of Cardiovascular and Thoracic Validation studies of PD-L1 IHC 22C3 pharmDx (Dako Omnis) for
Surgery, University of Ulsan College of Medicine, Asan Medical human non-small cell lung carcinoma (NSCLC) tissues
Center, Seoul, Republic of Korea, 5 Department of Pathology, L. Kramer1, G. Toland1, J. O'Brien1, C. Roach1, R. Welcher1, K.
University of Ulsan College of Medicine, Asan Medical Center, Kulangara1
1
Republic of Korea Agilent Technologies, Inc., USA
 Virchows Arch

Background & Objectives: PD-L1 IHC 22C3 pharmDx is indicated as taken to implement the outcomes nationwide, by starting a dialogue with
an aid to identify NSCLC patients for treatment with KEYTRUDA® health care professionals at a regional level.
(pembrolizumab) monotherapy. The assay is currently approved by the
FDA for use on the Autostainer Link 48 (ASL48) instrument. The intent Supported by Roche, Pfizer, AstraZeneca.
of these studies was to validate the assay for the Dako Omnis, an auto-
mated staining platform offering continuous delivery of patient slides. In
addition to precision studies, an important element was to show perfor- PS-13-018
mance equivalence between staining platforms for NSCLC specimens. Primary pleuropulmonary synovial sarcoma: clinico-pathological
Methods: The comparison study investigated the performance of PD-L1 features of 55 cases from a single tertiary care oncology centre
IHC 22C3 pharmDx (Dako Omnis) staining equivalence to the FDA- R. Kumar1, T. T. Nair1, V. Rao1, G. Hardas1, A. Janu2, B. Rekhi1, K.
approved PD-L1 IHC 22C3 pharmDx assay on ASL48. The same set Prabhash2, C. Pramesh3
1
of NSCLC specimens (n=84) was stained on both instruments, and then Department of Pathology, Tata Memorial Centre, India, 2 Tata Memorial
certified pathologists evaluated all specimens at the 1% and 50% cut-offs. Centre, India, 3 Department of Thoracic Surgery, Tata Memorial Centre,
In addition to the comparison study, NSCLC specimens were stained with India
PD-L1 IHC 22C3 (Dako Omnis) and were also evaluated for combined
precision (inter-lot, inter-instrument, inter-day). Background & Objectives: Primary pleuropulmonary synovial sarcoma
Results: The results from the comparison study demonstrated compara- (PPSS) is an extremely rare intra-thoracic malignancy, characterised by
ble staining between the ASL48 and Dako Omnis. At the 1% cut-off the specific chromosomal translocation[t(X;18)(p11.2,q11.2)]. The objective
point estimates for Negative Percent Agreement (NPA), Positive Percent of this study is to evaluate the clinicopathological features of PPSS from a
Agreement (PPA), and Overall Agreement (OA) were 99.0%, 98.5%, and single tertiary care oncology centre
98.8%, respectively. The results for 50% cut-off were: NPA was 95.5%, Methods: PPSS diagnosed between 2007-18 were retrieved from pathol-
PPA was 91.6%, and OA was 93.7%. At the 1% and 50% cut-offs, the ogy archives. Cases with known extra-thoracic primary were excluded.
combined precision study resulted in an OA of 97.9% and 100.0%, Clinico-radiological details were recorded and histopathological features
respectively. were reviewed.
Conclusion: Results from the comparison and combined precision stud- Results: A total of 55 cases of PPSS were identified, with age range 16-
ies indicate equivalent staining performance between PD-L1 IHC 22C3 80 years(mean age 39 years) and male: female ratio of 1.75:1. The tumour
pharmDx (Dako Omnis) and PD-L1 IHC 22C3 pharmDx on Autostainer was located in lung primarily{35(63.6%)}, while others were either pleu-
Link 48 at the clinically significant cut-offs. ral based(n=11) or infiltrating the chest wall(n=9) and mean tumour size
was 12cms( range: 3.3-20 cms). Monophasic variant was the commonest
histological subtype(43/48). Diffuse sheets or fascicles of the uniform
PS-13-017 spindle/ovoid cells with scanty cytoplasm and indistinct borders was seen
Best practice session on lung cancer molecular diagnostics in the in most of the cases. In addition hemangiopericytomatous vasculature
Netherlands to enhance testing proportions nationwide [77%], necrosis[44%] and focal myxoid change[23%] was also seen.
C. Kuijpers1, M. van den Heuvel2, A. van Lindert3, R. Damhuis4, S. On immunohistochemistry(IHC), Mic2(44/46) and Bcl2(41/45) were
Willems1 consistently expressed along with focal expression of epithelial
1
Department of Pathology, University Medical Centre Utrecht, The markers[pan CK(19/31) and EMA(16/28)]. Desmin and CD34 were con-
Netherlands, 2 Department of Lung Disease, Radboudumc, Nijmegen, sistently negative. Molecular confirmation was performed in 10 cases.
The Netherlands, 3 Department of Respiratory Medicine, University Chemotherapy was the main treatment modality and 8 underwent surgery.
Medical Centre Utrecht, The Netherlands, 4 Netherlands 5 patients died of disease and 22 had metastatic disease.
Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands Conclusion: We present one of the largest series on clinicopathological
features of PPSS, from this region. Establishing the diagnosis can be
Background & Objectives: Adequate and timely testing for genetic challenging, in the small biopsy specimen. Increasing awareness amongst
alterations in lung cancer is necessary to consider targeted therapy. pathologist, characteristic hemangiopericytomatous pattern and judicious
Previously, we demonstrated that in the Netherlands molecular testing use of IHC and molecular tests helps to ascertain the diagnosis.
was suboptimal in 2015, as 25% (EGFR/KRAS and ALK) to 50%
(ROS1) of patients were not tested according to guidelines, and notable
laboratory variation was present. Results were fed back to laboratories. In PS-13-019
a best practice session, we aimed to identify a process for best possible Usefulness of detection of amplification of PIK3CA and YEATS2
flow and highest possible testing proportions. genes using FISH in SqCC of lung
Methods: We invited pathologists, molecular biologists, pulmonologists, E. Lee1, H. Kim2, C. Kim2
1
and technicians from six laboratories/hospitals with highest testing propor- Naeun Hospital, Republic of Korea, 2 Korea University Guro Hospital,
tions to join a best practice session. Ultimately, four laboratories, two academ- Republic of Korea
ic and two non-academic, joined. Following a questionnaire, we discussed
their work flow and why they think their laboratory/hospital performs well. Background & Objectives: One of the characteristic of squamous cell
Results: We identified several stimulatory factors for molecular test- carcinoma (SqCC) of lung is amplification of distal portion of
ing: 1. discuss all metastatic lung cancer patients at multidisciplinary Chromosome 3q. Our previous study using whole genome microarray
meetings; 2. dedicated/specialized professionals; 3. short communi- for comparative genomic hybridization (CGH) and then NanoString
cation lines and clear agreements; 4. work culture of critical openness nCounter assay (NanoString) revealed that, among the genes located at
and honesty; 5. awareness and feedback on performance; 6. compre- distal portion of 3q, only PIK3CA and YEATS2 gene gains were associ-
hensive request by the pulmonologist of all genes to be tested; 7. to ated with poor prognosis. The aim of study is to investigate the usefulness
obtain sufficient tumour tissue: a. perform CT-scan earlier in process, of detection of amplification of PIK3CA and YEATS2 genes using fluo-
making it possible to collect larger biopsies in case a metastasis is rescence in situ hybridization (FISH) in SqCC of lung.
detected, and b. embed cytological material. Costs, without reim- Methods: We performed FISH in tissue microarray (TMA) block of 90
bursement, were seen as a prohibitive factor. cases of SqCC of lung. RP11-12L14 and RP11-245C23 (Empire
Conclusion: Several elementary steps (such as good communication) to Genomics, US) probes covered the locus of YEATS2 and PIK3CA, re-
improve adequate molecular testing were revealed. Initiatives will be spectively with orange colour was used. It was considered amplification
Virchows Arch

when there were ≥5 signals in each cell and more than 5 cells. The FISH Although several studies exist on the role of IDO-1 in human tissues,
results were compared to NanoString nCounter analysis results. little is still known about IDO-2 functions and particularly about its in-
Results: YEATS2 and PIK3CA gene were amplified in 37 (41%) and 29 volvement in non-small cell lung cancer (NSCLC) immunescape. 1,2
(32%) cases, respectively. SqCC of lung can be subdivided by 3q ampli- Methods: IDO-2 immunohistochemical expression was evaluated on
fied status using FISH, but amplified group didn’t show statistically sig- 193 formalin-fixed and paraffin-embedded resected NSCLC, both in neo-
nificant survival difference. plastic cells and in normal adjacent lung parenchyma. Correlations with
Conclusion: FISH is easily accessible method to detection of amplifica- clinical-pathological data, tumour-infiltrating lymphocytes (TILs), IDO-
tion of specific chromosome locus. We developed new FISH biomarker 1, programmed cell death ligand-1 (PD-L1) and patients’ prognosis were
to define YEATS2 or PIK3CA gene amplification status. However, using analysed.
FISH, amplified subgroup of SqCC of lung didn’t show clinically differ- Results: IDO-2 was chiefly enlightened at the interface between tumoural
ent prognosis. It is necessary further study to confirm clinical meaning of cells and tumoural stroma and at cell to cell junction; almost always
PIK3CA or YEATS2 genes amplified group of SqCC of lung. normal bronchial epithelium expressed IDO-2. Moreover, IDO-2 overex-
pression is closely related both to high PD-L1 among squamous cell
Supported by research funds from Korea University Guro Hospital. carcinomas (p=0.012) and to adenocarcinoma histotype (p<0.001).
Considerably, IDO-2 overexpression correlates with a worse NSCLC
prognosis (p=0.027), particularly in case of concurrent overexpression
PS-13-020 of IDO-1 (p=0.030) or high density of TILs (p=0.045), regardless of
Classic driver oncogene mutations in EGFR, ALK, ROS1 and PD-L1 histotype.
expression in chemonaive lung adenocarcinoma specimens: clinico- Conclusion: Our preliminary results have improved the knowledge
pathological correlations about IDO-2 in lung tissue and NSCLC, suggesting a function both in
F. Lunardi1, F. Pezzuto1, F. Fortarezza1, S. Vuljan1, G. Comacchio1, G. immune system modulation and in tumoural invasiveness. The
Pasello2, F. Rea1, F. Calabrese1 abovementioned interactions of IDO-2 with other microenvironmen-
1
University of Padua, Italy, 2 Veneto Oncology Institute - IOV, Italy tal molecules and their relationship with patients’ prognosis could
support both the assessment of their status on pathological report
Background & Objectives: Target somatic genome analysis (EGFR, and the introduction of combined immunotherapies as clinically use-
ALK and ROS1) and PD-L1 tumour proportion score (TPS) are used ful. Nevertheless, further studies are needed to better understand
for selection of first-line therapies in advanced lung cancer; however their IDO-2 role as potential biomarker in NSCLC.
frequency and significance in early stages in relation to the main morpho- References 1. van Baren, N. & Van den Eynde, B.J. Tryptophan-
logical and clinical characteristics is poorly reported. degrading enzymes in tumoural immune resistance. Frontiers in
Methods: The study population included 100 patients consecutively immunology 6, 34 (2015).
resected for primary pulmonary adenocarcinoma (stages I-II in 80% of 2. Metz, R., et al. IDO2 is critical for IDO1-mediated T-cell regulation
cases) without any neoadjuvant therapy in the period January 2017 - and exerts a non-redundant function in inflammation. International
January 2018, followed for a mean follow-up time of 15.7 months. immunology 26, 357-367 (2014).
EGFR mutational status and tissue immunohistochemical expression of
PD-L1 (clone: E1L3N), ALK (clone: D5F3) and ROS1 (clone: D4D6)
biomarkers were correlated with the main clinical and morphological PS-13-022
characteristics (histological pattern, proliferation index, lymphnode inva- Gender differences of nuclear morphometric and texture features in
sion, extension of necrosis and inflammatory infiltrate). small cell neuroendocrine carcinoma of the lung
Results: 27% of patients showed PD-L1 expression (12% with TPS ≥ K. Metze1, A. Castro de Mattos1, R. L. Adam1, J. B. Florindo1
1
50%), 4% of patients were positive for ALK and 2% for ROS1 (score 3). State University of Campinas, Brazil
PD-L1 expression was significantly associated with the solid histological
pattern and the proliferation index (p = 0.009 and p = 0.030). The posi- Background & Objectives: Some neoplasms show subtle differences
tivity for PD-L1 was also related to a higher frequency of recurrence (p = of the nuclear architecture between male and female patients. The
0.035). For ALK and ROS1, no significant differences emerged, except aim of this study was to compare morphometric and texture fea-
for a greater predisposition of females to express ROS1. EGFR mutations tures of nuclei of small cell neuroendocrine lung cancers (SCLC)
were more frequent in non-smoker patients (p = 0.002). between both genders.
Conclusion: The present study highlights PD-L1 as an intriguing predictive Results: The most striking finding was a difference of the nuclear area.
biomarker: its expression seems to be associated with increased tumour When comparing group means, tumour nuclei of male patients were
proliferation and aggressiveness as well as a higher risk of recurrence. about one third larger than those of female patients (p < 0,005). There
were no significant differences of the mean values of the Shannon entropy
of chromatin, but a small significant difference for the 75th percentile of
PS-13-021 the fractal dimension obtained by differential box counting (men: 2,174;
Indoleamine 2,3-dioxygenase 2 immunohistochemical expression in a women: 2,187; p = 0,001)
resected non-small cell lung cancer series Methods: We selected from our archive 49 consecutive SCLC patients
M. Mandarano1, G. Bellezza2, C. Volpi3, J. Vannucci4, I. Ferri2, G. with complete clinical data and follow-up. Routinely HE-stained brush
Mondanelli3, L. Cagini4, F. Puma4, M.L. Belladonna3, A. Sidoni2 cytology slides obtained at diagnosis were digitalized. After segmentation
1
Department of Experimental Medicine, Section of Anatomic Pathology of the nuclei, morphometric and nuclear texture features were measured
and Histology, Medical School, University of Perugia, Italy, 2 Department by in-house developed software.
of Experimental Medicine, Section of Anatomic Pathology and Conclusion: Our investigation suggests that in male SCLC patients
Histology, Medical School, University of Perugia, Italy, 3 Department larger tumour nuclei are more frequent, whereas chromatin texture
of Experimental Medicine, Section of Pharmacology, University of featreus show only very subtle differences between men and
Perugia, Italy, 4 Department of Thoracic Surgery, Medical School, women. A possible explanation for our findings could be the
University of Perugia, Italy presence of different SCLC subtypes with varying proportions
between both genders.
Background & Objectives: Indoleamine 2,3-dioxygenase 1 and 2 (IDO-
1 and IDO-2) are both implicated in immunomodulatory functions. Supported by FAPESP and CNPq.
 Virchows Arch

PS-13-023 Results: The overall PD-L1 tumour proportion score (TPS) of ≥50%, 49-
Immune-profilling depends on immunogenic collagen and mismatch 1%, and <1% of the keynote-010 trial and our cohort is 28.48%, 37.89%,
proteins to predict death and therapy in malignant mesothelioma 33.63%, and 29.05%, 33.16%, 37.79%, respectively. Tumours with a PD-
G. Morgantetti1, M. Balancin2, V. Martins3, J. T. De Miranda4, A. K. L1 TPS of ≥50% were not associated with patient gender, ethnicity, or
Assato3, N. A. de Souza5, A. P. Pereira Velosa6, W. Rosolia Teodoro7, biopsy type.
G. A. de Medeiros8, R. Falzoni9, A. M. Ab'Saber3, V. Capelozzi3 Conclusion: Our 22C3 LDT for the Ventana platform and the Keynote
1
University of Sao Paulo, Brazil, 2 Department of Pathology, Faculty of 001/010 display similar scoring distribution in NSCLC. Our cohort rep-
Medicine, University of São Paulo, Division of Pathology, Clinics resent a real-time, heterogenic group, outside of clinical trial setup. This
Hospital, Faculty of Medicine, University of São Paulo, Brazil, 3 support the notion that the LDT is clinically effective in NSCLC.
Department of Pathology, Faculty of Medicine, University of São
Paulo, Brazil, 4 Faculdade de Medicina, Universidade de Sao Paulo,
Brazil, 5 Division of Pathology, Clinics Hospital, Faculty of Medicine, PS-13-025
University of São Paulo, Brazil, 6 Hospital das Clinicas HCFMUSP, Lung cancer in young adults in Ceará Brazil
Faculdade de Medicina, Universidade de Sao Paulo, Brazil, 7 Faculdade D. Nunes Oliveira1, P. V. Pereira Motoyama2, V. M. Maia Amorim de
de Medicina, Universidade de Sao Paulo, Rheumatology Division, Morais2, R. Teófilo Parente Prado2, L. Matias Marques2, G. Bitu dos
Brazil, 8 Faculty of Medicine of Ribeirão Preto, University of São Santos Ponte2, S. Capelo Barroso Garcia2, S. Andrè de Souza Júnior2,
Paulo, Brazil, 9 Division of Pathology, Clinics Hospital, Faculty of J. Carneiro Melo1, R. L. Freitas de Almeida3, A. Rolim Campos3, F.
Medicine, University of São Paulo, Brazil Rocha Fernandes Távora4, J. Benoit Sabourin5
1
Department of Pathology, Postgraduate Program in Public Health,
Background & Objectives: Malignant mesothelioma (MM) is a highly Faculty of Medicine, University of Fortaleza, Brazil, 2 Faculty of
fatal disease with limited therapeutic options. The role played by micro- Medicine, University of Fortaleza, Brazil, 3 Postgraduate Program in
environment is evident, although unknow for Type V collagen (Col V) Public Health, Faculty of Medicine, University of Fortaleza, Brazil, 4
and mismatch repair (MMR) proteins. These elements have been evalu- Federal University of Ceara, Brazil, 5 Department of Pathology, Rouen
ated as well as the cross-talking as predictive and prognostic factors. University, France
Methods: Ninety MM patients were enrolled, located in pleural and
peritoneal serosae. We quantified through image analysis and employed Background & Objectives: Lung cancer (LC) has become one of the
immunofluorescence to evaluated Col V and immunohistochemistry to most lethal neoplasm in the world. Smoking is its main cause.
detect programmed death ligand 1 (PD-L1) expression in malignant cells Histologically it is divided into four types: squamous cell carcinoma,
(MCs), cells expressing the immune markers CD4, CD8 and adenocarcinoma, small cell carcinoma and large cell carcinoma. In
CD20,BAP1, and MMR proteins (MLH1, PMS2, MSH2, MSH6). Brazil, there is a shortage of information about LC histology, gender
Results: MCs-PD-L1 expression was 7/mm2,inflammatory cells express- differences and epidemiological tendencies. However, it is known
ing PD-L1 2.94/mm2,CD4+ 60/mm2, CD8+ 301/mm2and CD20+ 186/ that adenocarcinoma has become the most common histological sub-
mm2. Loss of BAP1 occurred in 61 (59%) cases. Col V fibers mean density type in the last 30 years especially among women. Concerning LC in
were 2.67/mm3. The mean MMR protein expression in tumour cells was young subjects studies show that there is a decreasing tendency in
MLH1 (713/mm2), PMS2 (957/mm2), MSH2 (1306/ mm2) and MSH6 smoking prevalence, but also that an early onset of smoking hampers
(855/mm2). A Cox multivariate model reliably predicted high risk of death its cessation during adulthood. The goal of this study is to analyse the
for MM with necrosis (p=0.01), high nuclear grade (p=0.003), low MCs- prevalence of LC among young people (≤ 40 years old) in the state of
PD-L1 (p=0.002), and inflammatory cells expressing PD-L1 (p=0.006), loss Ceara, Brazil.
of BAP1 expression p=0.005),low CD4+ (p=0.008), high MLH1 expres- Methods: This is a descriptive study. Data was collected from the
sion (p=0.002), and MSH2 (p=0.01), and high Col V fibers (p=0.004). website of Brazilian National Institute of Cancer (INCA). We select-
There was no significant difference between pleural and non-pleural disease. ed cases of LC in young patients recorded in Ceara between 2012 and
Conclusion: PD-L1 depends on the cross-talk between Col Vand tumour 2016.
mutation burden to promote cold-hot immunogenic switching and to Results: Twenty-nine cases of LC in young patients occurred in Ceara
predict death and target therapy in MM in pleural and non-pleural MM. during the selected period. 20 (69%) of them were in the metropolitan
region of Fortaleza, 3 (10.3%) in the countryside of the state, 2
Supported by FAPESP, CNPq, LIM17-FMUSP. (6.9%) in the Vale do Jaguaribe and Northeast regions of the state
each, and 1 (3.4%) for the North and Mid-south regions each. There
were 20 (69%) cases of LC in young women and 9 (31%) in young
PS-13-024 men. Regarding the histological subtypes, 18 (62.1%) cases did not
Immunohistochemical staining of PD-L1 using 22C3 laboratory de- report their subtype, 5 (17.2%) were adenocarcinomas, 2 (6.9%) were
veloped test (LDT) for Ventana platform: real-life statistical small cell carcinomas and mesenchymal tumours each, 1 (3.4)
validation undifferentiated/large cell carcinoma and non-specified carcinoma.
T. Neuman1, G. Vainer1 Thus, there was a predominance of non-small cell carcinoma
1
The Hebrew University - Hadassah Medical Center, Jerusalem, Israel (NSCC) (82%) in the analysed population.
Conclusion: We concluded that there is predominance of females among
Background & Objectives: Immunotherapy is a novel treatment in oncol- young people with LC and that NSCC is the most common subtype of LC
ogy. Pembrolizumab (MSD) is a monoclonal antibody against programmed as already described in the literature. Therefore, we found a need of more
cell death 1 that has been approved for use in many indications. In some multicentric studies that analyse other risk factors for the early develop-
indications a companion diagnostic by Dako (22C3 clone) for patient strat- ment of LC besides smoking and the prognosis for those patients that is
ification is required. Ventana's BenchMark immunohistochemistry (IHC) still controversial in the literature.
platform is widely used around the world. Our group described a 22C3-
based LDT for the Ventana platform, and showed its reliability and repro-
ducibility (2016). However, real-time data about the reliability is lacking. PS-13-027
Methods: Between July 2016 and March 2019, 1084 NSCLC patients Pulmonary metastases of gynaecological tumours
were evaluated at the Hadassah Medical Center for PD-L1 by immuno- A. Ok Atilgan1, M. Tepeoglu1, B. Ozdemir1
1
histochemistry. All patients were evaluated using the clone 22C3 LDT. Baskent University Faculty of Medicine Pathology Department, Turkey
Virchows Arch

Background & Objectives: The purpose of this study was to investigate Background & Objectives: Lung transplantation represents the treat-
the clinicopathological features of pulmonary metastasis of ment strategy for many end-stage pulmonary diseases. Chronic lung al-
gynaecological tumours. lograft dysfunction (CLAD) remains the major limit for long-term sur-
Methods: This is a retrospective study of forty-nine cases with pulmo- vival and its risk is increased by the occurrence of acute cellular rejection.
nary and/or pleural metastases were diagnosed between 2003 and 2018. A key role of IL-17 in the pathogenesis of lung alloimmune-induced
Clinical, pathological and survival data of these cases were reviewed. rejection has already been demonstrated, reporting T-lymphocytes as
Results: Serous carcinomas were the most histological type of primary the principal source of this cytokine. The aim of the study was to inves-
tumour (53%), followed by leiomyosarcoma (24%). Eighteen patients tigate IL-17 expression in different cell components of acute and chronic
(36,7%) had metastasis at the time of primary tumour diagnosis. The lesions occuring after lung transplantation in grafts of two different rat
remaining 31 patients were diagnosed with metastasis after initiation of strains.
primary cancer treatment, with a median presentation interval of 39 Methods: An orthotopic lung transplantation (OLT) was performed in 50
months after primary cancer diagnosis. The pulmonary and pleural me- rats (37 inbred Lewis into Fisher and 13 Sprague Dawley outbred rats).
tastasis presented synchronously in 7 patients, only pulmonary metastasis Histological features of primary graft dysfunction (PGD), acute and
in 22 patients, only pleural metastasis in 20 patients. Among patients with chronic rejection (AR, CR) (according ISHLT grading system) were eval-
pulmonary metastasis, 10 patients had a tru-cut biopsy from lung, 5 had uated and tissue IL-17 immunostaining was expressed as score (from 0 to
wedge resection, 8 had a lobectomy. Among patients with pleural metas- 3) in different cell types: lymphocytes, macrophages, airway epithelial
tasis, seventeen patients had pleural cytology, 5 pleurectomy, 4 pleural and stromal cells. IL-17 mRNA expression was also carried out in the
biopsy for diagnosis of metastasis The average size of the largest pulmo- bronchoalveolar lavages (BALs).
nary nodules was 3,1 cm and the number of nodules was 3,6. The median Results: PGD, moderate-severe AR and CR were detected in 16%, 30%
follow-up time was 47,8 months. Thirty-three patients (67,3%) had died and 22% of rats, respectively. IL-17 expression was higher in AR and CR
after metastasis. The Kaplan-Meier estimated overall survival at 2 years than PGD. IL17 expression was similar for AR and CR in macrophages
was 68% and disease-free survival at 2 years was 40%. We found that (median score value: 3), lymphocytes and epithelial cells (median score
primary tumour stage, number of metastatic nodules, the diameter of value: 2), while it was different in stromal cells (median score value: 0.5
nodules were identified as a prognostic factor for disease-free survival in AR and 3 in CR). A significant increase of IL-17 mRNA was observed
(p≤0,05). in AR than CR (4-fold). No differences were detected between the two
Conclusion: Complete surgical resection of metastasis is the most bene- experimental model strains.
ficial treatment which determines the outcome in these patients. Conclusion: IL-17 is overexpressed in allograft rejection, mainly in
more severe grade of AR and CR. Airway and stromal cells other
than inflammatory cells represent an important source of this cyto-
PS-13-028 kine, particularly in CR. Both rat strains seem viable animal models
Pulmonary sclerosing pneumocytoma: a comprehensive study of the to study and further investigate the role of IL-17-mediated pathway
molecular features of a series of six cases in Western (non-Asian) in lung transplantation.
patients
A. Panizo1, I. Amat1, L. Nova1, I. Fernandez1, T. Labiano1, M. Gomez-
Dorronsoro1 PS-13-030
1
Complejo Hospitalario de Navarra, Spain STK11 mutations are associated with lower PDL1 expression in lung
adenocarcinoma and is a candidate biomarker to predict the re-
Background & Objectives: Pulmonary sclerosing pneumocytoma (PSP) sponse of immunotherapy
is a rare benign tumour. The molecular profile of these tumours is not well N. Piton1, L. Claude1, F. Marguet1, E. Colasse1, A. Lamy1, F. Guisier1, M.
known. Salaün1, L. Thiberville1, J. Sabourin1
1
Methods: We performed a clinicopathological, IHC, and molecular study Rouen University Hospital, France
in six PSP. IHC was performed: beta-catenin, ALK, BRAF V600E,
ROS1, HER2, and PD-L1. Molecular tests included EGFR, KRAS, and Background & Objectives: The tumour expression of PDL1 is an im-
BRAF. FISH tests included ALK, and ROS1 rearrangement. perfect predictive biomarker of response to immunotherapy in lung can-
Results: All patients were women: median age of 50 yrs. (range: 29-73). cer. STK11 is frequently associated with KRAS mutation. Experimental
Mean size was 26 mm (range 15-45 mm). All tumours were located data suggest that STK11 impacts PDL1 expression, and that an impaired
within the right lung, and presented as single pulmonary nodule. Frozen STK11 is associated with lower PDL1 expression. To improve the selec-
sections (n=4): accurate diagnosis was 25%, 25% deferral rate and 50% tion of eligible patients for immunotherapy, we explored in further detail
were misdiagnosed as malignancy. All tumours were composed of more STK11 as a predictive biomarker of PDL1 expression and the association
than two growth patterns. EMA, TTF1, and PR were observed in both between the KRAS status of STK11 mutated tumours and PDL1
cells type. The surface cells showed also CK7, Napsin-A, and surfactant- expression.
A. IHC showed aberrant nuclear and cytoplasmic accumulation of beta- Methods: Lung adenocarcinomas harbouring a STK11 mutation were
catenin in the cuboidal cells in 3 cases, with even a significantly decreased consecutively included in the study group, while a control group lacking
or lack of expression in polygonal cells. Mutational analysis of EGFR, a STK11 mutation was randomly selected using a 26-gene panel with high
KRAS, BRAF and IHC/FISH for HER2, ALK, BRAF V600E and ROS1 throughput sequencing. The effects of STK11 mutations were predicted in
did not reveal molecular alterations. All cases were negative for PD-L1. silico. Tumours were immunostained for PDL1 using the E1L3N and
All patients were alive and well without recurrence at the time of last SP263 clones. The percentage of PDL1 positive tumour cells was
follow-up. evaluated.
Results: Fifty-two STK11 mutated tumours, including 28 with a KRAS
mutation, were compared to 42 STK11 wild-type tumours, including 17
PS-13-029 with a KRAS mutation. Mean percentage of PDL1 positive tumour cells in
Role of autoimmunity and interleukin-17 expression in acute and the STK11 mutated group was 9%, while 25% in the control group (p =
chronic lung allograft rejection: an experimental rat model 0.044). There was no statistically significant association between a KRAS
F. Pezzuto1, F. Lunardi1, S.E. Vuljan1, F. Fortarezza1, E. Cozzi1, F. Rea1, mutation and the expression of PDL1 in the STK11 mutated group. Five
F. Calabrese1 tumours expressing PDL1 harboured a STK11 mutation described as
1
University of Padua, Italy pathogenic.
 Virchows Arch

Conclusion: We confirmed that PDL1 expression is dramatically Col V expression in a murine model Col V immunized–induced lung
lowered in STK11 mutated lung adenocarcinomas compared to injury and human SSc.
STK11 wild-type tumours. In addition, we did not observe any asso- Methods: Histology, immunofluorescence, histomorphometry and qRT-
ciation between PDL1 expression and KRAS mutation. Despite the PCR in lungs of C57BL/6 mice (n=19) immunized with human Col V in
mechanism between STK11 activity and PDL1 expression remains Freund´s adjuvant was assessed and associated to surgical lung biopsy of
unclear, it seems that STK11 is a good candidate biomarker to predict patients with SSc (n=14) and controls (n=5).
the response of immunotherapy. Results: Lungs of Col V immunized animals showed a fibrotic interstitial
pneumonia. RT-PCR on whole lung mRNA confirmed overexpression of
genes which encoding chains of Col I [COL1A1, COL1A2] and Col V
PS-13-031 [COL5A1 and COL5A2] thus resulting in abnormal and increased deposi-
Microfluidic immunohistochemistry for rapid detection of diagnostic tion of the correspondent collagen fibers in tissue compared to controls [Col
and predictive biomarkers on non-small cell lung carcinoma I, 25.90 ± 3.315 vs. 5.571±0.5929, p=0.0003) and Col V, 7.53±0.41vs18.53
M. Procopio1, S. Brajkovic2, A. Leblond1, D. Dupouy2, A. Soltermann3 ±1.05, p<0.0001)]. Patients lung biopsies showed a SSc histologic pattern
1
University Hospital of Zurich, Switzerland, 2 Lunaphore Technologies and so demonstrated comparable abnormal and increased deposition of Col
SA, Switzerland, 3 Institute of Pathology and Molecular Pathology, I (44.49±0.93 vs. 30.62±1.34; p=0.01) and Col V (40.62±0.70 vs. 16.06
University Hospital Zurich, Switzerland ±1.39, p=0.002). Compared to normal lung, overexpression of IL-17 was
detected in lung lesions of the murine model (20.86±3.21 vs. 0.56±0.20;
Background & Objectives: Lung cancer is the most lethal tumour p<0.0001) and patients lung biopsies (3.455±0.36 vs. 1.72±0.19, p=0.01).
world-wide. Immunohistochemistry (IHC) is an essential tool in oncolog- Conclusion: Our findings highlight an overexpression of IL-17 and Col
ic pathology. Considering the increasing cancer incidence, a concomitant- V in lung associated fibrotic injury, thus providing one possible link
ly accurate and time-efficient IHC is clinically highly relevant. between autoimmunity and SSc.
The automated microfluidic staining device enables for a precisely con-
trolled immune-reaction to take place in an extremely short incubation Supported by Fapesp (2018/24210-8,2018/00415-0), LIM.
time; typically, a complete microfluidic IHC lasts less than 12 minutes on
frozen tissue section.
We aimed to develop and validate a microfluidics IHC for fast and accu- PS-13-033
rate biomarkers detection on formalin fixed paraffin-embedded (FFPE) Automating tumour proportion score computation for lung cancer
non-small cell lung carcinomas (NSCLC) - the most common lung cancer immunohistochemistry images
type. Here, we focus on the first part of the study aiming at optimizing the H. Qureshi1, P. O'Reilly2, J.P. Maxwell3, A. Kennedy2, A. Serag2, A. Ion-
microfluidic protocols. margineanu2, J. Diamond2, M. Saint Martin2, R. McMillan2, M. Salto-
Methods: Each protocol step - from antigen retrieval to counterstaining - Tellez4, P. Hamilton2
1
was automatized and optimised on the microfluidic device for all bio- Philips Digital & Computational Pathology, United Kingdom, 2 Philips
markers on representative FFPE NSCLC specimens to reach high-quality Digital & Computational Pathology, United Kingdom, 3 Queens
staining equivalent to a routinely used benchmark autostainer. University, Belfast, United Kingdom, 4 Queen's University Belfast,
Results: The optimised microfluidic IHC protocol achieved an analytical United Kingdom
performance comparable to standard staining on NSCLC for (i) differen-
tial diagnosis into adenocarcinoma (TTF1/CK7) or squamous cell carci- Background & Objectives: PD1-PD-L interaction (referred to as PD-
noma (p40/CK5-6) and (ii) prediction of immuno-therapy response (PD- L1) prevents the immune system from attacking tumour cells.
L1). Concomitantly, the total process time was shortened to less than Immunohistochemistry is used to detect PD-L1 as a guide for drug ther-
thirty minutes including the antigen retrieval pre-staining step, with a time apy. Detecting PD-L1 presence identifies patients that are likely to re-
reduction up to nine folds. spond to anti-PD-1 therapy. In Non-Small Cell Lung Cancer (NSCLC)
Conclusion: The microfluidic IHC resulted in fast automated high- PD-L1 is assessed using the Tumour Proportion Score (TPS). TPS is
quality staining for all assessed markers on NSCLC. Subsequent clinical computed as the ratio of the number of PD-L1 positive tumour cells to
validation on a large cohort will provide a diagnostic tool for biomarkers the total population of tumour cells.
detection in a turnaround time far beyond the existing autostainers. Methods: We used a deep neural network (UNET) ensemble to distin-
guish between the PD-L1 positive and negative tumour cells from the
Supported by Swiss Commission for Technology and Innovation Grant. non-tumour cells. UNETs are used to discriminate between complex tis-
sue types in the presence of PD-L1 immuno-reactivity. We employed
nuclei level as well as tissue structural level information to differentiate
PS-13-032 between cell types. The detected PD-L1 positive and negative tumour
Immunisation with type V collagen promotes fibrotic interstitial cells are counted and the TPS score is computed.
pneumonia of human systemic sclerosis in C57BL/6 mice via IL-17 Results: The technique provides reliable predictions of cell types
immune response with heat maps showing the classification of different cells. TPS
Z.A. Queiroz1, A.P. Pereira Velosa2, S. Catanozi1,3, A. dos Santos Filho2,4, scores provided by expert are compared with the TPS computed
S. de Moraes Fernezlian1,5, E. Miristene Eher1,5, I. Begalli Mendes1,4, J.T. using our technique. Highly accurate results are obtained with good
De Miranda1, E.R. Parra1,5, V.L. Capelozzi1,5, W. Rosolia Teodoro1,4 concordance with expert scores i.e. ≥ 85% (also Pearson Correlation
1
Faculdade de Medicina, Universidade de Sao Paulo, Brazil, 2 Hospital of 0.855).
das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Conclusion: We present a deep learning based technique for classifica-
Paulo, Brazil, 3 Department of Endocrinology, Brazil, 4 Rheumatology tion of cell types. Our technique offers a mechanism for screening of large
Division, Brazil, 5 Department of Pathology, Brazil numbers of cases thus relieving pressure on the pathologist and also offers
an opportunity for double scoring.
Background & Objectives: The immunogenic type V collagen (Col
V) and the proinflammatory interleukin (IL)-17 have been implicated
in the pathogenesis of multiple autoimmune diseases. Because IL-17 PS-13-034
and Col V are key contributors to Systemic Sclerosis (SSc) pathogen- Sclerosing pneumocytoma: pulmonary tumour in the last ten years
esis, in this report on SSc pathology, we have investigated IL-17 and F. Ramalhosa1, M.B. Pimentão1, M.J. Martins1, L. Carvalho2
Virchows Arch

1
Centro Hospitalar e Universitário de Coimbra, Portugal, 2 Institute of PS-13-036
Anatomical and Molecular Pathology, Faculty of Medicine of the Incorporating CTLA-4, CD274 and LAG3 single nucleotide poly-
University of Coimbra, Coimbra, Portugal morphisms (SNPs) to immune profile improves prediction of risk of
brain metastases and death in a Brazilian cohort of advanced non-
Background & Objectives: Sclerosing Pneumocytoma-Sclerosing small cell lung carcinoma
Hemangioma, type II pneumocytes origin, very rare benign lung J. Machado-Rugolo1, A. Fabro2, C. Aparecida Rainho3, C. Farhat4, V.
tumour, accounting 3% - 5% of benign rare lung lesions, usually Karen de Sá4, A. Carolina Scintini Herbst5, V. Cláudio Cordeiro de
without clinical symptoms, incidentally found (Lovrenski A et al, Lima6, E. Parra7, W. Rosolia Teodoro8, V. Luiza Capelozzi9
1
2019), has been diagnosed as 1/10 years - University Hospital of Clinicas Hospital, Faculty of Medicine, São Paulo State University,
Coimbra. The last case reported in March 2019. Botucatu, Brazil, 2 Department of Pathology and Legal Medicine, Ribeirão
Methods: Fifty-years-old woman, out-patient for tobacco cessation, Preto School of Medicine, University of São Paulo, Ribeirão Preto, Brazil,
3
with morning cough related to smoking habits. Very well Department of Genetic, São Paulo State University, Botucatu, Brazil,
4
circumscribed lesion was detected by X-Ray and MRI, with both Department of Pathology, University of São Paulo Medical School, São
pulmonary bronchoscopy and bronchial aspirate negative for Paulo, Brazil, 4 Department of Pathology, University of São Paulo Medical
tumoural cells. Sample received for frozen diagnosis and post- School, São Paulo, Brazil, 5 Department of Thoracic Surgery, A.C. Camargo
poned for ffpe. The patient was submitted to surgical resection Cancer Center, São Paulo, Brazil, 6 Medical Oncology Department and
afterwards. Translational Immune-Oncology Group, A. C. Camargo Cancer Center,
Results: Left Lower Lobe surgical biopsy - 20g and 4,5x3,6x2cm – São Paulo, Brazil, 7 Department of Translational Molecular Pathology,
cut surface revealed a well-circumscribed red-whitish haemorrhagic University of Texas MD Anderson Cancer Center, Houston, USA,
8
lesion. After the whole section and paraffin embedding, the histo- Faculdade de Medicina, Universidade de Sao Paulo, Rheumatology
pathology revealed two predominant histological patterns: sclerotic Division, 9 Faculdade de Medicina, Universidade de Sao Paulo,
and solid architecture. However, papillary and haemorrhagic regions Department of Pathology, Brazil
were also present. The tumour was composed by two cellular com-
ponents: luminal cuboidal cells and round “basal” cells, without Background & Objectives: To investigate whether polymorphisms of
cytological/nuclear atypia. The bulk of the tumour consisted of ei- immune checkpoints genes is associated with the tumour immune cell
ther haemorrhagic spaces delineated by the two cellular components profile and risk of brain metastases and death in Brazilian patients with
and sclerosing heterogeneous stroma. Stromal cells expressed advanced stage NSCLC.
vimentin and SMA and epithelial cells TTF1, CAM 5.2, CK7 and Methods: Seventy-five NSCLC patients were enrolled (37 adenocarci-
EMA; PR focally. nomas, 25 squamous cell carcinomas and 13 large cell carcinomas).
Conclusion: Surgical resection is the curative treatment that has been Using multiplex immunofluorescence and image analysis, we evaluated
assuring the benign behaviour of the tumour. Although, the follow-up programmed death ligand 1 (PD-L1) expression in malignant cells
remains necessary due to lymph node metastasis possibility, as referred (MCs), CD68+ macrophages, and cells expressing the immune markers
by Chien NC et al. (2009), who reported metastasis to the regional lymph CD3, CD8, CD57, CD45RO, FOXP3, PD-1, and CD20. We used high-
nodes in an 18-years-old male. throughput next-generation sequencing (NGS) to evaluate single nucleo-
tide variants in immune checkpoints genes CD274 (PD-L1), CTLA-4,
PDCDL1LG2 (PD-L2), LAG3 and B7H4 (VTCNI) in NSCLC by
PS-13-035 TruSeq Custom Amplicon Panel. A total of five single nucleotide poly-
PCR-based analysis of MET exon 14 skipping mutations in Russian morphisms (SNPs) were selected: rs2297136G/A (PD-L1), rs231775A/G
lung cancer patients (CTLA-4), rs7854303C/T (PD-L2), rs870849T/C (LAG3) and
G. Raskin1, M. Kholmatov2, N. Mitiushkina2, V. Tiurin2, A. Romanko2, rs10754339G/A (B7H4).
E. Imyanitov2 Results: Brain metastases was observed in 10% of patients and 31%
1
Academic A.M. Granov Scientific Center for Radiology and Surgical of them received adjuvant therapy. MCs-PD-L1+ expression was:
Technology, Russia, 2 N.N. Petrov Institute of Oncology, Russia <1% (40%), 1-10% (40%) and >10% (20%). Cells expressing the
immune markers CD3+ (330/mm2), CD3CD8+ (110/mm2), CD3-
Background & Objectives: MET exon 14 skipping (exon 14Δ) muta- PD1+ (85/mm2), CD68+ (58/mm2), CD68-PD-L1+ (2.5/mm2),
tions are associated with tumour sensitivity to a number of tyrosine kinase CD3CD45RO+ (260/mm2), CD3CD45FOXP3+ (260/mm2) and
inhibitors, however clinical testing for MET gene status remains CD20+ (46/ mm2). The frequency of genotypes was: CTLA-4
complicated. rs231775A/G (AA=40%; AG=25%; GG=10%), CD274
Methods: 1415 EGFR mutation–negative lung carcinomas (LCs) were rs2297136G/A (AA=32%, GA=26, GG=17%), PDCDL1LG2
tested for MET exon 14Δ using newly developed allele-specific PCR rs7854303C/T (CC=100%), LAG3 rs870849T/C (TC=32%,
cDNA-based method. CC=31%, TT=12%) and VTCN1 rs10754339G/A (AA=57%,
Results: MET exon 14Δ was identified in 35 LC cases, being GA=13%, GG=5%). A significant association was found between
associated with elderly age and non-smoking status. 34 (97%) PD-L1 and VTCN1 rs10754339 XX genotype (R=0.26; p=0.02)
out of 35 tumours carrying MET exon 14Δ showed preferential and PD-L1 rs2297136 GA genotype and MCs-PD-L1 (R=0.26;
expression of the mutated allele coupled with absence of the wild- p=0.04). Cox Regression analysis, controlled for age, histologic
type transcript. Sanger sequencing revealed genomic MET muta- types and adjuvant treatment, predicted low risk of brain metastases
tion in 24/35 (68.6%) cases with the exon 14Δ allele detected by and death for patients in N1 stage (p=0.01), CTLA-4 rs231775 AG
PCR. In contrast to published data, none of LCs with MET exon genotype (p=0.04), CD274 rs2297136 GA genotype (p=0.03), LAG3
14Δ allele carried mutation in PIK3CA gene. rs870849 TC genotype (p=0.04), low density of MCs-PD-L1
Conclusion: MET exon 14 skipping occurs in 2.5% of EGFR- (p=0.04) and high density of CD3+CD8+ lymphocytes (p=0.04).
negative LCs. Several methodological issues should be taken into Conclusion: Incorporating immune checkpoints genes polymorphisms
account in order to ensure the reliable diagnosis of MET exon 14 ito immune profile score improves prediction of brain metastases and
skipping. death in a Brazilian cohort of NSCLC and may be promise as combining
target therapy.
This work has been supported by the Russian Science Foundation [grant
number 17-75-30027]. Supported by FAPESP, CNPq.
 Virchows Arch

PS-13-037 Germany) and cooling trap from Lenz Laborglas Instrumente (Wertheim,
Cicatricial lung fibrosis is not a variant of organising pneumonia Germany) placed to a thermos with a cooling agent. EBC samples were
M. Samsonova1, A. Cherniaev1, K. Mikhajlichenko1 collected from patienta (12 - COPD, 16 - NSCLC) and 31 healthy vol-
1
Pulmonology Scientific Research Institute, Russia unteers (12-smokers/19-nonsmokers).
EBC sample (~1 mL) was transferred into polypropylene low
Background & Objectives: Recently variant labelled "cicatricial" orga- temperature-resistanttest-tubes with a low protein-absorbing surface
nizing pneumonia (CiOP) has been described by Yousem (2017) and and lyophilized up to complete dryness and reconstituted in 0.05 M
Churg et al (2018), which characterised with a combination of ordinary NH4HCO3 buffer (pH 8.0) to final protein concentration 1 mg/mL.
organizing pneumonia (OP) and dense fibrous tissue. The aim of our Then EBC samples were hydrolysed with modified porcine trypsin
research was to describe 5 cases of CiOP. (Promega, USA). All samples (injection volume 2 L) were analysed in
Methods: 5 patients (4 male, 1 female) with the age ranged 41-57 yrs triplicate on a nano-HPLC Agilent 1100 system (Agilent Technologies,
with histologic pattern of CiOP were included. Santa Clara, CA, USA) combined with a 7-T LTQ-FT Ultra mass spec-
Results: Patient complaints were cough, dyspnea (5/5), weakness (2/5). trometer (Thermo Electron, Bremen, Germany) using a nanospray ion
On CT scans of the chest, there were ground glass opacities with fibrosis source (positive mode, high voltage +2.1 kV).
and cavities (1/5), perilymphatic dissemination (2/5), a cavity with Results: Proteomic analysis of the EBC revealed more than 200 different
perifocal infiltration (1/5) or interlobular septal thickening with ossifica- proteins groups. Cytoskeletal keratins type II and type I were confirmed
tion (1/5). Histological examination revealed linear masses or nodules of as an invariant part of EBC proteome for all the samples from patients
dense fibrous tissue, some of them were ossified. Recognizable OP with (COPD and lung cancer). Also cytoskeletal keratins are the major protein
prominent eosinophilic infiltration was found only in 1 case which looked components of the EBC for smokers, as well as for non smoking healthy
like organizing eosinophilic pneumonia. In two cases with perilymphatic individuals. It is shown that EBC proteome analysis was significantly
dissemination on CT, there were loose perivascular granulomas com- deeper for samples collected with washing step from the tube walls.
posed of histiocytes and lymphocytes. In two cases we saw atypical The optimised collection was performed with both commercial devices
adenomatous hyperplasia and mucous hyperplasia of alveolar epithelium. (RTube™, ECoScreen®) and laboratory built cooling trap. Comparative
And in one case dendriform ossification was more prominent than fibrous EBC proteome analysis was performed for patients from different groups
masses, in this case, there was progression on CT during the half of year. (COPD, lung cancer, smokers and non smoking healthy individuals). The
Conclusion: In cases of CiOP we did not always see granulation plugs in approach enable us to identify additional set of EBC proteins (POTE,
the lumen of respiratory bronchioles and alveolar ducts. Ossification is NUCKS 1 and other) specific for lung cancer.
the most common feature of CiOP. We propose that CiOP is a reparative Conclusion: An optimised method for EBC sample collection for
reaction which could be the result of various lesions. Dendriform ossifi- further proteome profiling by high resolution mass spectrometry
cation previously described by many authors could be the variant or the was developed. It is shown that the results of the proteome analysis
end stage of CiOP. significantly differ for samples collected with and without washing
step. Both protocols should be used for more deep EBC proteome
profiling from patient. Comparative EBC proteome analysis with an
PS-13-038 optimised sample collection protocol enable us to reveal EBC pro-
Exhaled breath condensate proteome profiling for lung cancer diag- teins specific for lung cancer.
nostics by high resolution mass-spectrometry
V.Sergeeva1, A. Yusupov2, N. Zakharova3, M. Indeykina3, A. Bugrova3, The study was supported by RFBR project no. 18-29-09158 MK.
K. Fedorchenko4, A. Ryabokon4, M. Kushaeva5, E. Anaev5, V. Barmin6,
O. Pikin6, A. Kononikhin7
1
Emanuel Institute for Biochemical Physics, Russian Academy of Sciences, PS-13-039
Russia, 2 Emanuel Institute for Biochemical Physics, Russian Academy of Specific morphological features of pulmonary adenocarcinoma in
Sciences, Moscow Institute of Physics and Technology, Russia, 3 Emanuel plutonium production workers
Institute for Biochemical Physics, Russian Academy of Sciences, Russia, G. Sychugov1, E. Kazachkov1, T. Azizova2, A. Sychugov1
4 1
Emanuel Institute for Biochemical Physics, Russian Academy of South Ural State Medical University, Russia, 2 Southern Urals
Sciences, Lomonosov Moscow State University, Russia, 5 Research Biophysics Institute, Russia
Institute of Pulmonology, Federal Biomedical Agency of Russia, Pirogov
Russian National Research Medical University, Russia, 6 Herzen Moscow Background & Objectives: Epidemiological studies prove increased
Oncology Research Institute, Russia 7 V.L. Talrose Institute for Energy risks of lung cancer and chronic obstructive pulmonary disease in
Problems of Chemical Physics, Russian Academy of Sciences, Emanuel workers exposed to internal alpha-radiation. However various mechanis-
Institute for Biochemical Physics, Russian Academy of Sciences, Russia tic, morphological and pathogenetic aspects of radiation-induced pulmo-
nary diseases are still insufficiently investigated.
Background & Objectives: The main cause of high mortality from lung Examination of autopsy tissues from deceased workers internally exposed to
cancer is late diagnosis because early symptoms may be absent or non- alpha-particles revealed that ‘hot particles’ were distributed in the lungs
specific (e.g. cough and shortness of breath). Timely diagnosis significantly inhomogeneously. The highest carcinogenic risk per 1 Gy of alpha-
increases the life expectancy of patients. Invasive methods of investigation of radiation was found for adenocarcinoma (AC) which is the most common
the lungs (bronchoscopy, aspiration ultrasonic transbronchial needle, etc.) can histological type of lung cancer in plutonium production workers.
not be fully used for screening. Computed tomography is an encouraging, but Previously it was demonstrated that ALK rearrangements, expression Ki-
rather expensive and resource-intensive method of diagnosis. Exhaled air and 67 and oncogene c-Myc are predictive tumour markers.
exhaled breath condensate (EBC) analysis become popular and relevant. The Methods: We investigated morphological characteristics of pulmonary AC
aim of the study is to developed and optimise methods for EBC sample based on autopsy specimens collected from 22 Mayak PA workers (group 1)
collection for further proteome profiling by high resolution mass spectrome- taking into account total lung absorbed dose from internal alpha-radiation
try. Comparative EBC proteome analysis is performed for patients from and duration of radiation exposure. Group 2 included 15 AC cases found in
different groups (COPD, lung cancer, smokers and non smoking healthy individuals who had never been working at the Mayak PA.
individuals) to identify EBC proteins specific for lung cancer. The tissue sections were incubated with monoclonal antibodies against
Methodes EBC was collected using RTube™ (Respiratory Research, Ki67 proliferating cell nuclear antigen (clone MIB-1), ALK (clone D5F3,
Inc., Austin, TX, USA), ECoScreen® (Erich Jaeger GmbH, Hoechberg, Ventana) and oncogenic antibody c–Myc (clone EP121).
Virchows Arch

Results: ALK gene rearrangement and c-Myc expression were negative showed loss of TRAF7 expression and high expression of L1CAM at
in 100% cases of group 1. least in 1 of 2 MPM cases with TRAF7 gene mutation.
Considerable decrease of proliferative cell activity in tumour specimens Conclusion: The abnormality of the TRAF7 gene may be involved in the
of group 1 compared to group 2 was found. development of MPM, unlike malignant mesothelioma of the peritone-
Conclusion: No significant associations with ALK and c-Myc bio- um. Immunohistochemistry of TRAF7 and L1CAM would be useful for
markers were observed for lung cancer. detection of such MPM with TRAF gene mutation.
The specific Ki-67 expression in AC cells suggest specific biological
mechanisms involved in lung cancerogenesis following prolonged inter-
nal radiation exposure. PS-13-043
Correlation of predominant type of lung adenocarcinoma with TNM
stage of disease
PS-13-041 L. Vučković1, M. Miladinovic1, F. Vukmirovic1, M. Golubovic1
1
Raman-fluorescent characteristics of bleomycin-induced pulmonary Medical Faculty, University of Montenegro, Clinical Center of
fibrosis Montenegro
I. Chernov1, E. Malysheva2, S. Timofeev2, V. Kukushkin3, Y. Kirillov1
1
Tyumen State Medical University, Russia, 2 City Hospital of Moscow Background & Objectives: Tumour staging is essential to patient care,
#40, Russia, 3 Institute of Solid State Physics Russian Academy of reasrch and control of the disease. The stage of disease at the time of
Sciences, Russia diagnosis is a reflection of the rate of growth, extension of the neoplasm,
type of tumour and the tumour-host relationship. Since the TNM staging
Background & Objectives: Raman spectroscopy is used to diagnose system is one of the most important prognostic factor, we analysed wheth-
different diseases, including benign and malignant neoplasms. The meth- er there is a statistically significant difference in distribution of predom-
od uses a laser beam which interacts with the tissue and scatters light, inant histological type of lung adenocarcinoma (AD) compared to the
creating a fluorescent effect. This is then detected by a spectrometer and TNM stage of disease.
captured in graph form. Methods: We analysed 148 patients with invasive AD of the lung. We
Methods: The study was performed on 30 male rats, under protocol, where defined the predominant type using the IASLC / ATC / ERS criteria
they were injected intratracheally with a single dose of bleomycin 10 mg / kg (solid, acinar, papillary, micropapillary, lepidic and enteric type). The
body weight. The control group consisted of 10 rats which were injected the stage of the disease was determined according to the eight edition of
same way with the same quantity of saline. The lungs were examined TNM classification.
through histology and spectroscopy, using a specific device, on days 7, 14, Results: The most common types of AD were solid (35.1%), acinar
and 30 after the administration of bleomycin and saline. (31.1%) and papillary (16.9%). The most of patients were in T2a stage
Results: Day 7: the initial fluorescence (9.5 thousand units), the maxi- of disease. Metastases in lymph nodes were found in 51 patients. Distant
mum (14 thousand units) and residual fluorescence, similar to the control metastases were found in 16.2% of patients. Using Fisher's nonparametric
group. test (p = 0.009) there was no statistically significant difference in the
Day 14: the spectrum of initial fluorescence in the range of 20.0- 29.1 distribution of types of lung AD in relation to T and N status.
thousand units with a gradual increase in the values of fluorescence and a Statistically significant difference in relation to M status was confirmed.
high level of its local maximum (32.5 thousand units) Conclusion: Determination of TNM stage of cancers is considered as the
Day 30: two local maxima of fluorescence (70.0 and 83.0 thousand units), most important prognostic factor. According to our results there are no
high values of initial (49.2 thousand units) and residual fluorescence. statistically significant differences in the distribution of prevalent types of
Conclusion: This study suggests that there is a correlation between lung AD in relation to T and N status, while metastases in distant organs
changes in Raman fluorescent characteristics and pulmonary tissue re- most common are given by solid and acinar types.
modelling in the course of an experiment, which is expressed in the
progression of sclerosis.
PS-13-044
Expression of Carbonic Anhydrase IX as a novel biomarker for dif-
PS-13-042 ferentiating pleural mesothelioma from non-small cell lung
Malignant pleural mesothelioma with TRAF7 gene mutation carcinoma
T. Tsujimura1, A. Sato1, M. Yuki1, Y. Shinohara1, J. Takeshita2, H. B. Xu1, T. Zou1, Z. Liu2
Aburatani2, Y. Sekido3 1
Roswell Park Cancer Center, USA, 2 State University of New York at
1
Hyogo College of Medicine, Japan, 2 University of Tokyo, Japan, 3 Aichi Buffalo, USA
Cancer Center Research Institute, Japan
Background & Objectives: Malignant mesothelioma (MM) is an ag-
Background & Objectives: It has been recently reported that the tumour gressive tumour with poor prognosis. Histological diagnosis of MM with
necrosis factor receptor-associated factor 7, TRAF7, gene was frequently limited tissue can be challenge, particularly for epithelioid type of MM.
mutated in adenomatoid tumour and well differentiated papillary meso- Immunohistochemical (IHC) stains with panel of antibodies are useful for
thelioma of the peritoneum, but no mutations were found in malignant confirmatory diagnosis of MM. Carbonic anhydrase IX (CAIX) is a
mesothelioma of the peritoneum. Although the analysis of TRAF7 gene transmembrane protein and is overexpressed in variety solid tumours.
mutation may be useful to differentiate these tumours of the peritoneum, In our routine IHC work-outs for tumour of unknown origin, we discov-
the abnormality of the TRAF7 gene has not been well investigated in ered a robust cytoplasmic membrane expression of CAIX in pleural MM.
malignant pleural mesothelioma, MPM. In this study, we further investigate the sensitivity and specificity of CAIX
Methods: The TRAF7 gene in 61 cases of either clinical samples or expression in large scale by using tissue microarrays of mesothelioma and
established cell lines of MPM was analysed by next generation sequenc- non-small cell lung carcinoma (NSCLC), respectively.
ing. The expression of TRAF7 and L1 cell adhesion molecule, L1CAM, Methods: Unstained TMA slides composed of 56 cases of pleural MM
which is a molecule in the NF-kB pathway activated by TRAF7 mutation (38 epithelioid type and 16 sarcomatoid type) and 79 cases of lung
was immunohistochemically examined. cancerNSCLC (including 42 lung adenocarcinoma, 37 lung squamous
Results: TRAF7 gene mutations were found at the WD40 domain of the cell carcinoma) from year 1993-2013 were used for IHC stains performed
C-terminus in 2 of 61 (3.3%) MPM cases. Immunohistochemistry clearly on DAKO Omnis platform using pre-diluted mouse anti-human Ab
 Virchows Arch

against CAIX (Bio-SB). CAIX IHC staining was graded semi- PS-14-001
quantitatively by two independent surgical pathologists. Performance assessment of Multiplex Ligation-dependent Probe
Results: All 38 cases of epithelioid MM (including epithelioid compo- Amplification (MLPA) in malignant pleural effusions (MPE)
nent of biphasic MM) are positive for CAIX, 89% (34/38) cases displayed L. Antonangelo1,2,3, C. Silvèrio Faria2,4, R. Oliveira da Rocha5,4,6, A.
diffuse and strong reactivity in tumour cells. Two sarcomatoid MM and Mendes Nascimento7,4,6 , G. Francisco da Silva Carvalho5,4,6, A.
most of sarcomatoid component in biphasic MM (5/16) were negative Torchio Dias5,4,6, L. Domenici Kulikowski5,4,6
1
and remaining showed low to moderate expression level of CAIX. There Hospital das Clinicas, Brazil, 2 Faculty of Medicine, University of São
is no distinction in terms of expression level and patterns between MM Paulo, SP/Brazil - Laboratorio de Investigacao Medica - LIM 03, Brazil,
3
and benign mesothelial cells. Among NSCLC, 76% (32/42) adenocarci- Department of Patology, Brazil, 4 Department of Pathology, Brazil,
5
nomas and 57% (21/37) squamous cell carcinoma are completely nega- Hospital das Clinicas - Laboratorio de Investigacao Medica - LIM 03,
tive, whereas the remaining cases show focal weak to moderate expres- Brazil, 6 Universidade de Sao Paulo, Brazil, 7 Hospital das Clínicas -
sion of CAIX. Laboratorio de Investigacao Medica - LIM 03, Brazil
Conclusion: Our study demonstrate that expression of CAIX has
high sensitivity (100%) in detecting pleural EM, which is equal or Background & Objectives: Malignant pleural effusion (MPE) is a
better than that of current commonly used mesothelioma markers. common occurrence in medical practice, and its diagnosis is a chal-
The specificity of CAIX is at compatible ranges to that of com- lenge for clinical laboratories. It is known that most of metastatic
mon mesothelial markers for differentiating epithelioid MM from tumours to pleura presents chromosomal gains and losses, which
lung adenocarcinoma, but is much higher for differentiating lung can be detected by cytogenomic techniques. The aim of this study
squamous cell carcinoma. Therefore, we believe that CAIX can be was to evaluate the performance of Multiplex Ligation-dependent
an additional useful marker for immunohistochemical work ups of Probe Amplification (MLPA) to identify genomic abnormalities of
MM, particularly for epithelioid mesothelioma. tumour cells in pleural effusions (PE).
Methods: We evaluated a total of twenty-eight pleural effusion samples:
17 samples from patients with MPE and 11 samples with effusions of
PS-13-045 benign etiology. DNA was extracted using QIAMP DNA Blood kit
Diagnostic value of TTF-1, CK5/6, CK7, CD56, Chromogranin A (QIAGEN, Valencia, California) and cytogenomic investigation was per-
and Synaptophysin expression in differential diagnosis of small cell formed using MLPA with P175-B1 Tumour Gain kit (MRC-Holland®,
and non-small cell lung carcinomas in biopsies Amsterdam, The Netherlands), searching for pathogenic CNVs and
L. Zakhartseva1, O. Guz1, G. Chytaieva1, Y. Zakhartsev2 BRAF specific point mutations. The results were analysed with
1
National Medical Bohomolets University, Ukraine, 2 Kiev City GeneMarker® software (SoftGenetics, LLC, State Collage, PA).
Oncology Center, Ukraine Results: From the 17 cases of MPE, MLPA identified genomic changes
in 5 cases: 2 cases with BRAF (7q34) p.V600E (c.1799T> A) point
Background & Objectives: Nowadays lung carcinomas are most of- mutation; 1 case with MYC duplication (8q24); 1 case with BRAF
ten verified on small biopsies that causes some difficulties in routine p.V600E (c.1799T> A) point mutation and MDM2 (12q15) duplication
diagnostics. Immunohistochemistry (IHC) plays a key role, but IHC and 1 case with concomitant duplications in CDK4 (12q14), MDM2
markers significance varies in different types of lung carcinomas. (12q15) and CCND1 (11q12). Control group presented normal results
Purpose of the study is diagnostic value estimation of antibodies in MLPA investigation.
panel (Thyroid transcription factor-1 (TTF-1), Cytokeratin 5 (CK5/ Conclusion: MLPA technique was efficient to detect several different
6), Cytokeratin 7 (CK7), Cluster of Differentiation (CD56), genomic abnormalities in 5 MPE samples with at least 30% of tumour
Chromogranin A, Synaptophysin) for accurate verification of differ- cells in the cytological results and provides a valuable tool to detect
ent lung carcinomas. pathogenic variants especially in MPE cases.
Methods: Patients’ mean age was 58.01±2.09, ranged from 30 to 79.
Biopsy samples of 121 lung carcinomas have been studied: 56 Supported by FAPESP and LIM 03.
(46.28%) adenocarcinomas, 36 (29.75%) squamous cell carcinomas,
and 29 (23.97%) small cell carcinomas. In 76 (62.81%) cases there was
an additional verification on aftersurgery samples. Standard IHC methods PS-14-002
were applied: tumour’s immunophenotype was defined in all samples Usefulness of type V collagen and α2β1-integrin in the cytological
using TTF-1, CK5/6, CK7, CD56, Chromogranin A, and Synaptophysin. diagnosis of pleural liquid biopsy
Results: 54 (96.43%) adenocarcinomas were CK7-positive, 50 (89.29%) L. Antonangelo1,2,3, W. Rosolia Teodoro4,5, C. Silvèrio Faria2,6, Z.A.
were TTF-1-positive. 5 (17.24%) small cell lung carcinomas were TTF-1- Queiroz4, L. Ramos da Silveira7,8, A.P. Velosa7,8, V. Capelozzi9
1
positive, 9 (31.03%) tumours – CK7-positive, and 3 (10.34%) – CD56- Hospital das Clinicas, Brazil, 2 Faculty of Medicine, University of São
positive. All squamous cell carcinomas were TTF-1-negative, most of Paulo, SP/Brazil - Laboratorio de Investigacao Medica - LIM 03, Brazil,
3
them expressed CK5/6. Chromogranin A or Synaptophysin was Department of Patology, Brazil, 4 Faculdade de Medicina, Universidade
expressed in 15 (51.72%) samples of small cell lung carcinoma, both de Sao Paulo, Brazil, 5 Rheumatology Division, Brazil, 6 Department of
neuroendocrine markers – in 12 (41.38%), Pathology, Brazil, 7 Faculty of Medicine, University of São Paulo, SP/
none – in 2 (6.89%) cases. Morphological and ICH features were identical Brazil, Brazil, 8 Laboratorio de Investigacao Medica - LIM 17 -
in biopsy and aftersurgery samples in 96.69% observations. Rheumatology Division, Brazil, 9 Department of Pathology, Faculty of
Conclusion: Lung biopsy studies allow accurate diagnostics of different Medicine, University of São Paulo, Brazil
pulmonary carcinomas. IHC antibodies panel (TTF-1, CK 5/6, CK7,
CD56, Chromogranin A, and Synaptophysin) is the most appropriate. Background & Objectives: The identification of metastatic cells in se-
The use of some individual markers may lead to diagnostic errors, since rous effusions has prognostic and therapeutic implications, thus leading to
IHC expression in non-differentiated tumours may vary significantly. permanent investigation to improve the usual diagnostic procedures, in-
cluding immunofluorescence. Collagen type V (Col V) is a fibrillar col-
lagen up-regulated in the stroma of different malignant tumours, which
Tuesday, 10 September 2019, 09:30 - 10:30, Agora 3 promotes cell migration and motility. The aim of the study was to evaluate
PS-14 | Cytopathology the usefulness of Col V and its receptor α2β1-integrin, in detecting met-
astatic cells in samples of pleural effusion.
Virchows Arch

Methods: Malignant pleural effusion (MPE, n=12) and benign pleural PS-14-004
effusion (n=4) were processed in a cytospin cytocentrifuge, fixed in 95% Rapid on-site evaluation by imprint cytology for liver core-needle
ethanol and stained for Papanicolaou. Diagnoses were established by biopsies, is it really needed?
clinical, cytological and histological evaluation. Immunofluorescence A. Armutlu1, O.C. Taskin1, L. Oguzkurt2, P. Firat1
1
double staining and image analysis were employed to detect and quantify Koc University Hospital, Department of Pathology, Turkey, 2 Koc
Col V and Integrin expression. University Hospital, Department of Radiology, Turkey
Results: From MPE, eight patients were men (median age, 50y) and 4
patients were women (media age, 45y). The cellular composition of Background & Objectives: Rapid on-site evaluation (ROSE) of core-
MPE included nucleated total cells (mean, 1937/mm3), neutrophils needle biopsies by imprint cytology is used to increase diagnostic ade-
(mean, 65.54/ mm3), macrophages (mean, 32.54/mm3) and mesothe- quacy. This study aimed to document the efficacy of ROSE for liver core-
lial cells (mean 1.90 / mm3). Tumour cells from all MPE showed a needle biopsies.
strong red and green birefringence respectively from Col V and Methods: Archieved records of our department between January 2017
Integrin coinciding with an increased expression when compared to and April 2019 were retrospectively reviewed. Clinicopathological fea-
negative reactive mesothelium (mean 24.15 and 12.11 px, respective- tures, patient demographics, number of passes and final diagnoses were
ly). A similar expression of Col V and Integrin was found among retrieved from the pathology reports and hospital database.
tumours originated from breast (n=5), gastrointestinal tract (n=3), Results: 119 cases with core-needle biopsies of liver were retrieved.
kidney (n=1) and lung cancer (n=3) (mean, 18.31 and 13.10; mean Male/female ratio was 1.3/1, with a mean age of 61.8 (range 20-89) years.
26.54 and 11.78; mean 25.18 and 11.79 ± 0.14 and mean 24.14 and ROSE was performed in 72 cases. Mean number of passes was 3,8 for cases
12.11, respectively, p>0.05). with ROSE (vs. 2,6 without ROSE).Final diagnoses were malignant in 64 [6
Conclusion: Collagen V and α2β1-integrin were useful in detecting hepatocellular carcinoma (HCC), 58 other], benign in 6, and non-diagnostic
single-tumour cells dispersed among inflammatory reaction and might in 2 cases (%2,7) with ROSE [vs. 44 malignant (2 HCC, 42 other), 2 benign
be a promising biomarker for the identification of malignant cells in and 1 non-diagnostic (%2,1) without ROSE].Two cases with ROSE were
pleural liquid biopsy. non-diagnostic due to abundant necrosis, whereas non-diagnostic case with-
out ROSE represented sampling error. Two of three non-diagnostic cases
Supported by FAPESP, CNPq, LIM 17 and LIM 03. were diagnosed as HCCs with repeat biopsies, one did not have histologic
follow-up, but was clinically suspicious for recurrent HCC.
Conclusion: Advantage of ROSE for liver biopsies was not remarkable
PS-14-003 in this study, because no significant difference was observed in terms of
Urinary cytology suspicious for urothelial carcinoma (2015): re-eval- diagnostic adequacy between both groups, except for one case with sam-
uation, according to the Paris System for reporting urinary cytology pling error. All of the non-diagnostic cases were primary hepatocellular
(2016) and correlation with follow-up lesions, biopsied with or without ROSE. High number of passes may be
D. Argyropoulou1, C. Dahlstedt Ferreira1, H. Oliveira Coelho1, N. explained with selection bias. Further studies with larger series and pro-
Ramos2, M. Carvalho2, M. Brito1 spective design are needed to draw sharper conclusions.
1
Department of Pathology, Hospital Garcia de Orta, Portugal,
2
Department of Urology, Hospital Garcia de Orta, Portugal
PS-14-005
Background & Objectives: Urinary cytology remains a pertinent, Evaluation of the selective study of BRAF V600E mutation in thyroid
non-invasive method to patient care and monitoring. The introduc- fine needle aspirative cytology
tion of a more precise terminology with the Paris System allows a M. Bella-Cueto1, C. Padilla1, P. Serret1, M.C. Ramos1, R. Carrera1, C.M.
standardised reporting way and a better correlation with clinical Blazquez1, M.I. Agustín1, M. Escoda1, V. Perez1, F.X. Guirao1, I. Capel1,
parameters. Our aim was to re-evaluate the urinary cytology spec- M. Rigla1, N. Combalia1
imens reported during 2015 in our Institution as “suspicious for 1
Parc Taulí Hospital Universitari. Institute d'Investigació i Innovació
urothelial carcinoma”, according to The Paris System for Parc Taulí. Universitat Autònoma de Barcelona, Spain
Reporting Urinary Cytology and correlate those with patients’ fol-
low-up. Background & Objectives: BRAF p.V600E is a known mutation of
Methods: All (n=378) the 2015 urinary cytology slides of liquid thyroid papillary carcinoma (PTC), with variable frequency according to
based urinary cytology, reports and clinical follow-up data were re- the subtype. In our centre, its determination has been incorporated to fine
trieved from the files. 61 urinary cytology slides previously classified needle aspirative cytology (FNAC) by pyrosequencing (PSQ) in cases of
(2015), as “suspicious for urothelial carcinoma” were blindly Bethesda III category with cytological atypia and of Bethesda V category
reviewed by two different pathologists. A diagnosis was given based suspicious of PTC. Currently, immunohistochemical study is also available.
on the Paris System for Reporting Urinary Cytology and the results Objective: To determine the feasibility, suitability and contribution to the
were analysed. diagnosis of BRAF p.V600E determination in these selected thyroid
Results: The 61 urinary cytology specimens previously classified (2015) FNAC.
as “suspicious for urothelial carcinoma” were re-classified (Paris Methods: Retrospective review of the frequency and results of the BRAF
System,2016) as: High Grade Urothelial Carcinoma (HGUC-16), p.V600E study by PSQ in thyroid FNAC performed in our centre, from
Atypical Urothelial Cells (AUC-5), Other malignancies (OM-1), Low January 2015 to August 2018, with diagnoses of Bethesda III with atypia or
Grade Urothelial Neoplasm (LGUN-21) and Negative for High Grade Bethesda V, and with histological correlation. Immunohistochemical study
Urothelial Carcinoma (NHGUC-18). with VE1 antibody was performed in cases with surplus available material.
When correlated with clinical follow up (cystoscopy + cytology/biopsy) Results: 1092 thyroid FNAC were performed in 895 patients, 47 of
the new re-classification (Paris System,2016) displayed a sensitivity of which met the inclusion criteria. In 25 cases the study was discarded
87.2% for urothelial carcinoma and a specificity of 92% for HGUC. because the atypia observed was not suggestive of PTC or the material
Conclusion: In our series, the implementation of the Paris System for was follicular-patterned. Of the 22 remaining, only 16 had enough mate-
Reporting Urinary Cytology provided a more specific diagnosis in all rial, resulting in 6 mutated cases (37.5%), 4 of them with a confirmed
specimens that had been previously classified just as “suspicious for PTC in the subsequent thyroidectomy, and the other 2 pending surgery.
urothelial carcinoma”, with a sensitivity of 87.2% for urothelial malignant Positive results with VE1 were obtained in the 4 surgical specimens and
lesions and a specificity of 92% for HGUC. in two FNAC cell blocks.
 Virchows Arch

Conclusion: We estimate that the study of BRAF p.V600E mutation in round to ovoid cells with scant cytoplasm embedded in the myxoid
selected thyroid FNAC (Bethesda III with atypia and Bethesda V) can matrix and prominent branching capillary network were seen in all
improve the diagnostic accuracy in 6/16 cases (37.5%) of our series. FNA smears and in all corresponding sections of CNB. FISH anal-
ysis disclosed rearrangement involving FUS gene in 5 cases, and
was inconclusive/borderline in 2 cases.
PS-14-006 Conclusion: This study illustrates that characteristic cytological and his-
Diagnostic value of the European Thyroid imaging reporting and tologic features of myxoid liposarcoma together with specific cytogenetic
data system in stratifying the malignancy risk of Bethesda category abnormality allows definitive diagnosis in small volume biopsies.
III nodules Compared to open biopsy, small volume biopsies are most cost-effective,
I. Dimitrova1, A. Shinkov1, R. Kovatcheva1, R. Ivanova1 outpatient procedures with negligible risks for serious complications.
1
Department of Endocrinology, Medical University of Sofia, Bulgaria

Background & Objectives: Ultrasound-guided fine-needle aspiration PS-14-008

(US-FNA) with cytology is the pivotal method for differentiating Breast hemangioma: malignant neoplasm simulator in breast cancer
malignant from benign thyroid nodules. Nevertheless, Bethesda screening
category III remains a clinical challenge. Ultrasound has an essen- J. Fraga1, F. Ramalhosa1, A. Lai1, C. Faria1, B. Pimentão1, H. Moreira1,
tial role in detecting malignant nodules and recently the most em- R. Almeida1, V. Almeida1, C. Oliveira1, G. Fernandes1
1
inent thyroid societies published ultrasound malignancy risk strat- Centro Hospitalar e Universitário de Coimbra, Portugal
ification systems. We aimed to evaluate prospectively the diagnos-
tic value of the Thyroid Imaging Reporting and Data System Background & Objectives: Hemangiomas are benign vascular tu-
established by the European Thyroid Association (EU-TIRADS) mours that arise from malformation of mature blood vessels, and
in a series of Bethesda category III thyroid nodules. are usually incidental findings. They are usually microscopic lesions,
Methods: For a period of one year 1000 nodules in 783 patients were discovered in 1.3% of mastectomies for carcinoma and in 4.5% of
prospectively evaluated according to EU-TIRADS and then submitted to biopsies for benign breast lesions and rarely manifest clinically as
US-FNA. Cytological reports were based on the Bethesda system and palpable lesions.
nodules classified in category III were included in this study. Methods: We present an 81-year old woman which screening mam-
Sensitivity, specificity, negative predictive value (NPV), positive predic- mography revealed a circumscribed lobulated nodule. Ultrasound
tive value (PPV) and accuracy of EU-TIRADS were calculated compared located the lesion on the periphery of the right upper quadrant of
to histology. We used the high risk category (EU-TIRADS 5) as a cut off the right breast, with 19x11mm, hypoechogenic and heterogeneous,
for test positivity. with a slight increase in size from previous imaging study 2 years
Results: Seventy one nodules were classified in Bethesda category III. ago. Physical examination of her breast and axilla were normal.
The mean nodule diameter was 13.83±10.28 mm. Thirty three nodules Given the suspicion of malignant lesion, cytological evaluation was
underwent surgery and 12 (36.3%) were malignant. Eleven (91.7%) of performed.
the malignant nodules were classified in EU-TIRADS 5. Sensitivity, Results: It was performed a Fine Needle Aspiration Cytology
specificity, NPV, PPV and accuracy of EU-TIRADS were 91.66%, (FNAC) which smear revealed a sample with hematic background
42.8%, 90.0%, 47.8% and 60.6%, respectively. Between the four equally and rare cellular elements, raising the question of the lesion being
weighted ultrasound characteristics of EU-TIRADS microcalcifications of vascular nature given the imagiological correlation. After inclu-
had the highest sensitivity and specificity. sion in paraffin of the product obtained by aspiration, a vascular
Conclusion: EU-TIRADS is reliable in the malignancy risk stratification neoplasia was observed, consisting of thin and branched vessels,
of Bethesda category III nodules and can rule out malignancy with high coated endothelial cells with positivity to CD34 and CD31 and neg-
certainty. ativity to podoplanin.
Conclusion: Benign or malignant mesenchymal tumours of the breast
are rare. Breast hemangiomas are rare, and usually appear as well-
PS-14-007 delimited round or oval nodules at mammography, as case presented.
Small volume biopsy in the diagnosis of myxoid liposarcoma On ultrasonography, hemangiomas might present as solid,
H. Domanski1, J. Köster1 hypoechoic or cystic areas with small bright echoes due to calcifica-
1
Department of Genetics and Pathology, Division of Laboratory tion and fibrous septations. Given the clinical–pathological difficulty
Medicine, Lund, Sweden of diagnosing vascular lesions in the breast, extensive excisional
biopsy is recommended.
Background & Objectives: An increasing use of minimally invasive
diagnostic procedures and the growing availability of diagnostic
ancillary tests has resulted in better acceptance of small volume PS-14-009
biopsies such as fine needle aspiration (FNA) and core needle Retrospective analysis of pap smears in patients diagnosed with en-
biopsy (CNB) as the first-line approach in the diagnosis of soft dometrial carcinoma: a 5-year study from an emergency university
tissue lesions. Myxoid liposarcoma accounts for 15% to 20% of hospital in Romania
liposarcomas. The most common site of involvement is in the deep T.A. Georgescu1, A.C. Lisievici2, A. Dumitru3, M. Sajin4,5
1
soft tissue, preferably of the thigh. This neoplasm carries a specific Department of Pathology, Bucharest Emergency University Hospital,
cytogenetic abnormality which helps to render a correct diagnosis. Romania, 2 Carol Davila University of Medicine and Pharmacy,
Methods: Seven patients were admitted to the Sarcoma Center in Lund Bucharest, Romania, 3 Department of Pathology, "Carol Davila"
underwent FNA and CNB of deeply seated soft tissue masses. University of Medicine and Pharmacy, Bucharest, Romania, 4 SUUB,
Examination of routine stained FNA smears and histological sections Romania, 5 UMF Carol Davila, Romania
was completed by fluorescence in situ hybridization (FISH) analysis on
FNA specimen. Background & Objectives: Babes-Papanicolaou test (often abbrevi-
Results: Six tumours were located in the thigh and 1 in the lower ated Pap smear) has proven to bean efficient screening method for
leg. All of the examined small volume samples were correctly potentially precancerous and cancerous lesions of the uterine cer-
diagnosed as myxoid liposarcoma. Clusters and sheets of small, vix. In the aftermath of its success, endometrial cancers are
Virchows Arch

showing a rising trend worldwide and several attempts have been any significant benefit in this cohort of unique and challenging thyroid
made in order to establish a potential role of this analysis in the FNA specimens in our academic setting.
early diagnosis of endometrial carcinoma. However, detection of
glandular lesions can be limited by issues related to both sampling
and interpretation. PS-14-011
Methods: This is a 5-year retrospective study undertaken within the Alveolar rhabdomyosarcoma in adults: cytological evaluation
Pathology Department of the Emergency University Hospital in K. Ikemura1, S. El Hussein2, L. Hakima2, S. Khader2
1
Bucharest Romania, in which we aim to rescreen the initial Pap Montefiore Medical Center, USA, 2 Montefiore Medical Center/Albert
smears of patients already diagnosed with endometrial carcinoma Einstein College of Medicine, USA
on biopsy or hysterectomy specimens, for the detection of normal,
atypical or malignant glandular cells. Our goal was to correlate the Background & Objectives: Rhabdomyosarcoma (RMS) is an aggres-
presence of glandular cell abnormalities on conventional Pap smears sive and extremely rare soft tissue malignant neoplasm in the adult pop-
with the histopathological type, grade, stage and clinical outcome of ulation. Fine needle aspiration biopsy (FNA) is often performed to diag-
endometrial carcinoma. nose primary and metastatic tumours. Cytological evaluation of FNAs
Results: Among the total of 183 patients who underwent hyster- can be challenging due to overlapping morphologic features of various
ectomy for endometrial carcinoma, 32.79% had a Pap result 1-3 entities and limited biopsy material available. The objective of this study
months prior to surgery. Cervical cytology was reported as fol- is to highlight the cytomorphologic features of RMS and raise awareness
lows: 31.67% patients had atypical endometrial cells, 21.67% pa- of the differential diagnostic difficulties.
tients had atypical glandular cells and 46.66% patients had no Methods: A 28-year-old otherwise healthy female presented with a 2.0 x
glandular cells abnormalities. The presence of glandular cell ab- 1.5cm polypoid mass in the right nasal ala. FNA and follow-up surgical
normalities was more strongly associated with serous carcinoma biopsy were performed. There was no imaging done prior to the FNA.
(85.71%) than with endometrioid carcinoma (55.76%). Almost all Results: The FNA smears showed dispersed and loosely cohesive aggre-
patients with no glandular cell abnormalities (95.83%) had low- gates of hyperchromatic cells with uniform round-oval nuclei, inconspic-
grade tumours. uous nucleoli, and scant cytoplasm. Marked crushing artifact and nuclear
Conclusion: Although not even remotely as sensitive for screening karyopyknosis were also noted. Immunohistochemical stains were posi-
endometrial carcinoma, identification of atypical glandular cells on tive for myogenin and MyoD1, while negative for AE1/3, CD45, S100,
Pap smears warrants further investigations in order to rule out MelanA, HMB45, CD99, Synaptophysin and Chromogranin. FISH anal-
neoplasia. Our study revealed that higher-grade tumours (especially ysis showed a translocation in (1;13)(p36;q14) (FOXO1A), which
serous carcinomas) are strongly associated with atypical glandular established the diagnosis of alveolar RMS.
cells, while lower-grade tumours either lack any glandular modifi- Conclusion: RMS is rare and often clinically misdiagnosed in the adult
cations or featureminor cellular changes with high inter-observer population. The cytomorphologic features of “small round blue cells”
variability. raise a wide differential diagnosis and the distinction between alveolar
and embryonal RMS can also be challenging. It is essential for
cytopathologists to be aware of the differential diagnosis and integrate
PS-14-010 morphologic, immunohistochemical, and cytogenetic analysis to accu-
Correlation between initial and consensus cytology review of rately classify these tumours.
"STAT" thyroid surgical pathology cases: a 5-year experience
N. Javakhishvili1, B. Hunt2, K. Arispe2, A. Farooq2, T. Giorgadze2
1
David Tvildiani Medical University, Tbilisi, Georgia, 2 Medical College PS-14-012
of Wisconsin, USA Solid papillary neuroendocrine carcinoma of the breast -
cytopathological features in 36 cases
Background & Objectives: In our academic Institution, clinically T. Kawasaki1,2, R. Katoh3,4, T. Kondo3, K. Horibe2, H. Nagai2, M.
challenging thyroid lesions and lesions with indeterminate preopera- Takahashi5
1
tive fine needle aspiration (FNA) diagnoses are triaged by overnight Saitama Medical University International Medical Center, Japan, 2 National
“STAT” processing with final diagnosis provided the next day. Hospital Organization Nagoya Medical Center, Japan, 3 University of
Completion thyroidectomy is performed the day after surgery if need- Yamanashi, Japan, 4 Ito Hospital, Japan, 5 Nagoya University, Japan
ed. We evaluated if the diagnostic accuracy of FNAs can be improved
by consensus review. Background & Objectives: The purpose of this study was to clarify the
Methods: Twenty-eight consecutive FNA specimens from this cohort of cytological profiles of solid papillary/neuroendocrine mammary carcino-
challenging cases (2011-2015) were blindly reviewed by 2 ma in situ (SP/NE-CIS).
cytopathologists with consensus Bethesda category diagnosis obtained Methods: We cytopathologically analysed 26 fine needle aspiration
and compared to the original diagnosis. Both diagnoses were correlated (FNA) smears and 17 nipple discharge smears obtained from 36
with final surgical pathology findings. All discrepant cases were re- Japanese patients with SP/NE-CIS.
reviewed to determine the cause of discrepancy. Results: The background of the FNA smears was clear in 17 cases (65%),
Results: Twenty-eight FNA specimens were obtained from twenty-six mucoid in five cases (19%), hemorrhagic in three cases (12%) and necrotic
separate nodules of twenty-two patients. Initial diagnoses were discrepant in one case (4%). Cellularity was high in 25 cases (96%) and low in one case
in 7 cases (4 due to interpretation, 3 from sampling). Consensus diagnoses (4%). Characteristically, SP/NE-CIS cells were loosely arranged in three-
were also discrepant in 7 cases (3 due to interpretation, 4 from sampling). dimensional, solid clusters or singly dispersed. Well-developed vascular
Discrepant cases included 2 cases of PTC, 6 cases of NIFTP and 1 case of cores with or without cancer cells were occasionally recognized. Cancer
follicular adenoma. cells were polygonal or spindle-shaped with a fine-granular, abundant cyto-
Conclusion: No difference in discordance rate between initial and con- plasm. Nuclei with finely granular chromatin were round or ovoid and often
sensus cytology and follow-up histology diagnoses were found in this eccentrically located (plasmacytoid appearance). Mitotic figures were infre-
cohort of challenging thyroid lesions. Discrepancies were all “undercalls” quent. Nuclear grade was estimated to be low in 88% (23/26) of the samples.
associated with scant cellularity, minimal microfollicular component or Most nipple discharge smears had fairly-low cellularity with poorly-
background lymphocytic thyroiditis. The cases of PTC did not show preserved cell clusters in markedly hemorrhagic backgrounds, although
diagnostic cytologic features on review. Consensus review did not offer two (12%) were extremely cellular with cytological characteristics similar
 Virchows Arch

to those of the FNA smears. Preoperative cytological cancer diagnoses were immunocytochemistry or molecular assays. Noteworthy, all used agents
made in 46% (12/26) of FNA smears and 0% (0/17) of nipple discharge have a full validation to immunocytochemistry and molecular analysis.
smears. Immunohistochemistry for neuroendocrine markers (chromogranin Purpose: We pointed to implement that method to pulmonary cytology and
A and synaptophysin) confirmed the neuroendocrine nature of this tumour in to assess its diagnostic efficiency and quality of immunocytochemistry.
adequate cytological specimens as well as histological specimens. Methods: All mucous rich or bloody specimens were Cyto Rich
Conclusion: SP/NE-CIS has distinctive cytopathological features and Red fixed and watery pleural effusions were Cytospin Collection
can, therefore, be diagnosed as a carcinoma with neuroendocrine features Fluid fixed. After centrifuging a supernatant was removed and a
in most FNA and some nipple discharge smears by cytologic examination sediment were rinsed again. LBC smears were performed with BD
employing immunohistochemical techniques. We stress that a breast le- Thin Prep, then were stained H&E, Papanicolau, Giemsa and 2
sion with these features may be in situ and not invasive, and also that there unstained slides were stored in fridge. Immunohistochemistry was
is a risk of under-diagnosis. based on Benchmark XT Roche Diagnostics. We applied concur-
rent double immunostaining for CD4 and CD8 using two separate
Supported by Grants-in-Aid for Scientific Research (16K08654 & chromogens (DAB/Red) and other conventional antibodies.
16H00668) from the Japanese Ministry of Education, Culture, Sports, Results: LBC approach provided clear, thin smear with steadily dispersed
Science and Technology and National Hospital Organization (NHO) cell allowing easy counting of cell fraction. High quality smear helped in
Grant (H29-NHO-01). diagnosis of cancer cases in bronchial washings and also pleural effusion.
Bronchial brushing specimen granted vortexing and sedimentation pro-
vided high quality material. We met CD4 positive reactivity in alveolar
PS-14-013 macrophages what hampered counting of CD4/CD8 ratio but that obser-
Risk of malignancy in salivary gland lesions using the Milan system vation, especially small macrophages meaning, shed a new light on CD4
for reporting salivary gland cytopathology: a single Institution positive cells ratio in flow cytometry.
experience Conclusion: LBC method is a good solution improving quality of pul-
S. Lajara1, C. Castrodad1, D. Guerrero1, S. El Hussein1, S. Khader1, A. monary cytology and providing a foundation for immunocytochemistry.
Colanta1, L. Hakima1
1
Montefiore Medical Center/Albert Einstein College of Medicine, USA
PS-14-015
Background & Objectives: Fine needle aspiration (FNA) is a routine PD-L1 IHC 22C3 pharmDx expression on cytology preparations
part of the initial evaluation of salivary gland lesions. Most published from non-small cell lung carcinoma (NSCLC): precision and inter-
literature report high sensitivity, specificity and accuracy, but the results observer analysis
vary greatly, which is likely due to study design variations and lack of J. Musser1
1
uniform reporting. The Milan System for Reporting Salivary Gland Agilent Technologies, USA
Cytopathology (MSRSGC) aims to standardize reporting and serve as a
guide for pathologists and clinicians. Background & Objectives: Background: PD-L1 expression is required
This study investigated the utility of the MSRSGC by evaluating its by a companion diagnostic test (PD-L1 IHC 22C3 pharmDx) for identi-
ability to predict the risk of malignancy (ROM). fication of Pembrolizumab-responsive NSCLC patients, currently ap-
Methods: A total of 383 salivary gland FNA reports over a three-year proved for resected biopsy or core specimens. Cytology material may
period were reviewed and reclassified blindly according to the MSRSGC be the only specimen available in advanced NSCLC malignancies and
categories. The ROM was determined by comparing the corresponding is emerging as a useful specimen type for PD-L1 assessment.
surgical resections in 181 cases. Objective: Precision of PD-L1 IHC 22C3 pharmDx on formalin-fixed,
Results: The ROM for the corresponding categories were: 3.8% for paraffin-embedded (FFPE) cytology specimens, including fine-needle
Non-Diagnostic, 20% for Non-Neoplastic, 42.9% for Atypia of aspirates (FNA), bronchial wash (BW), and pleural fluid (PF).
Undetermined Significance (AUS), 1.6% for Benign Neoplasm, Methods: A blinded and randomized Intra-site study was designed for
17.9% for Salivary Gland Neoplasm of Uncertain Malignant testing variables on 48 cytology specimens, with 3 operators each oper-
Potential (SUMP), 91% for Suspicious for Malignancy and 100% ating a unique autostainer instrument immunostaining with PD-L1 IHC
for Malignant. The sensitivity, specificity, positive and negative pre- 22C3 pharmDx assay over 3 non-consecutive days.
dictive values were: 91.7%, 98.5%, 97.1%, and 95.8%, respectively, Inter-observer precision was evaluated using the same assay on 103 cy-
similar to published data. tology specimens and scored by multiple observers.
Conclusion: These ROMs are within the wide range of reported values in Tumour Proportion Score (TPS) was utilized for determining PD-L1
literature. The comparatively high ROM for AUS (42.9%) can be attrib- positive/negative agreement for ≥1% and ≥50% tumour thresholds.
uted to the cases of low-grade mucoepidermoid carcinomas and lympho- Results: Positive, negative and overall agreements were determined by
mas, which provide diagnostic challenges on cytology. The low resection Bootstrap method. All bootstrapped 95% confidence interval lower
rates (26/102 for non-diagnostic and 10/62 for non-neoplastic) likely bound values met an acceptance criterion of ≥85%. Overall agreement
account for the relatively low and relatively high ROMs for non- values for both studies, analysed for both diagnostic cut-offs, ranged from
diagnostic (3.8%) and non-neoplastic (20%) categories, respectively. 93% to 97.7%.
Conclusion: FFPE cytology preparations from NSCLC can be success-
fully stained and scored for PD-L1 expression using PD-L1 IHC 22C3
PS-14-014 pharmDx assay. There was very high overall agreement for both studies.
Application of liquid base cytology to bronchopulmonary cytology
P. Lewitowicz1, Y. Sleiman2, A. Horecka-Lewitowicz1
1
JKU University in Kielce, Poland, 2 St. Raphael Memorial Specialistic PS-14-017
Hospital in Czerwona Gora, Poland Anal carcinoma screening strategy based on cytology, hrHPV bio-
markers testing and conventional anoscopy
Background & Objectives: Conventional approach based on direct O. Ondic1, J. Nemcova2, K. Cerna3, J. Smahelova4, F. Rob5
1
smear possesses many restrictions which could be dissolved by LBC. Medical Faculty Pilsen, Czech Republic, 2 Biomedical Center of the
Another type of fixation with lysis of erythrocytes et mucus diluting Faculty of Medicine in Pilsen, Czech Republic, 3 Sikl's Department of
provides a cell suspension as a top quality output to followed thin smears, Pathology, Faculty Hospital in Pilsen, Czech Republic, 4 National
Virchows Arch

Reference Laboratory for Papillomaviruses and Polyomaviruses, Conclusion: The rates of the positive predictive value for the DS immu-
Czech Republic, 5 2nd Medical Faculty Charles University in Prague nochemistry were directly associated by the severity of the cervical le-
and Bulovka Hospital, Czech Republic sions. So, the P16/Ki67 dual stain could be an effective method to assist in
the diagnosis of squamous intraepithelial lesions.
Background & Objectives: The anal carcinoma (AC) screening is war-
ranted in high-risk populations, particularly in HIV positive men having
sex with men (HIV-MSM). In the absence of high-resolution anoscopy, a PS-14-019
cytologically-based approach is possible. Sensitivity and specificity of Study of the morphology and reproducibility of brushed colorectal
anal cytology are limited. Co-testing of high-risk human papillomavi- polyps utilising liquid-based cytology
ruses (hrHPV) biomarkers could triage patients harbouring high-grade D. Aninos 1 , D. Pouloudi 2 , N. Kavantzas 2 , A.C. Lazaris 2 , D.
anal lesion (HGAIN) for further examination (conventional anoscopy) Tranoudakis 1 , K. Christina 1 , N. Asimaki 1 , I. Panayiotides 3 , G.
and treatment more precisely. We tested this combined screening ap- Thomopoulou1
1
proach in Czech HIV-MSM. Department of Diagnostic Cytopathology, General University Hospital
Methods: Anal LCB (liquid-based cytology) samples were collected from of Athens "Attikon", School of Medicine, National and Kapodistrian
172 HIV-MSM. Upon cytology reading, hrHPV transcription activity was University of Athens, Greece, 2 First Department of Pathology, Medical
studied together with HPV genotyping and DNA methylation of selected School, National and Kapodistrian University of Athens, Greece, 3
tumour suppressor genes (TSG) associated with HPV induced carcinogene- Second Department of Pathology, General University Hospital of
sis. Some patients complied with recommended follow-up anoscopy. Athens "Attikon", School of Medicine, National and Kapodistrian
Results: 93 samples rendered abnormal cytology (ASC-US, LSIL, ASC- University of Athens, Greece
H, and HSIL). Transcription activity of hrHPV was detected in 55 pa-
tients. HPV 16/18/45 was detected in 53 patients. Methylation silencing Background & Objectives: The purpose of this study was to assess
of TSG was present in 38 patients. ASC-H or HSIL cytology was found the inter- and intraobserver agreement in cytological brushing from
in 12 patients paired with hrHPV transcriptional activity in 10 with si- colorectal polyps, with the use of ThinPrep® technique, as well as
multaneous DNA methylation of TSG in 4 patients. Anoscopy detected to emphasize cytomorphologic criteria needed for the diagnosis and
no visible lesion in any of 75 patients (including 9 with ASC-H or HSIL categorization of colonic adenomas.
cytology). Methods: A total of 193 brushing specimens from 118 patients with colo-
Conclusion: 1. The results indicate an increased efficiency of AC screen- rectal polyps were examined with corresponding histopathological diagno-
ing based on cytology - hrHPV biomarkers co-testing. 2. No AC case was sis. ThinPrep slides were evaluated by two skilled cytopathologists. After
identified using conventional anoscopy. 3. Also, no precancerous lesion establishment of the criteria, three additional cytopathologists without rela-
was found in any of the patients with ASC-H/HSIL cytology result. 4. In tive experience in liquid-based colorectal cytology, examined the same
those patients digital anorectal examination is warranted. smears to determine interobserver variability. Each reviewer was asked to
categorize each slide into the following categories: within normal limits/
This study was supported by the National Sustainability Program, pro- blunt cytology, adenoma with low grade intraepithelial neoplasia, adenoma
vided by the Ministry of Education Youth and Sports of the Czech with high grade intraepithelial neoplasia and adenocarcinoma. The
Republic (AZV17 – 31777A). intraobserver variability was also evaluated by all five observers.
Results: The overall interobserver agreement was nearly perfect with k
value of 0.9350 during the checking round and again nearly perfect with k
PS-14-018 values ranged from 0.8469 to 0.9253 respectively to the other diagnostic
Predictive value of dual stain P16/Ki67 for detection of high-grade rounds (P<0.0001). Adenoma with high grade intraepithelial neoplasia
cervical intraepithelial lesions was the most difficult category to identify because of minimal deviation
P. Mentzelopoulou1, A. Magkana1, M. Magkana2, M. Sotiropoulou3, K. from adenocarcinoma. Regarding intraobserver agreement, it was nearly
Pappa2, M. Papaefthimiou1 perfect with respective k values ranged from 0.8554 to 1.00 in all diag-
1
Department of Cytology, Alexandra Hospital, Athens, Greece, nostic rounds (P<0.0001).
2
Department of Colposcopy of 1st Clinic of Gynaecology and Conclusion: The overall inter- and intraobserver agreement was nearly
Obstetrics of University of Athens, Greece, 3 Department of perfect for brush cytology of colorectal polyps using Thin Prep method.
Histopathology, Alexandra Hospital, Athens, Greece Liquid based cytology appears to be highly accurate and reliable cytological
method for diagnostic approach of colorectal polyps and could be added as a
Background & Objectives: The purpose of this study is to estimate the complementary technique to biopsy for the improvement of the diagnosis.
predictive value of the combined P16/Ki67 dual staining (DS) in high
grade squamous intraepithelial lesions.
Methods: We evaluated the performance of P16/Ki67 immunochemistry PS-14-020
(Cintec Plus, dual stain) in 64 women with histological diagnoses of high- Parathyroid adenoma - fine-needle aspiration cytology correlation
grade cervical intraepithelial lesions 2/3 (CIN 2/3) in colposcopy-directed with surgical specimens
biopsies or cone biopsy results. All women had a previous liquid-based C. Quadros1, M. Mendes-de-Almeida1
1
cytology specimen (PreservCyt, ThinPrep Paptest). The cytological diag- CHULN - Hospital de Santa Maria, Portugal
noses included 10 cases of atypical squamous cells of undetermined sig-
nificance (ASCUS), 28 cases of low-grade squamous intraepithelial le- Background & Objectives: Parathyroid adenoma (PA) is suspected when
sion (LSIL) and 26 cases of high-grade squamous intraepithelial lesion a single gland is enlarged and hyperfunctioning. The cytological aspects of
(HSIL). the PA are very similar to the normal parathyroid tissue and may mimic other
Results: Out of the 64 cases, 48 cases were P16/Ki67 positive (75%) and non-neoplastic lesions. We present a correlation study between cytologic
16 cases were negative (25%). Out of those 48 cases, DS immunochem- aspects and the respective resection specimens regarding PA.
istry positive, 22 cases were diagnosed by HSIL cytological diagnoses Methods: Retrospective data pertaining to the 2016-2018 period were
(PPV 84.62%), 20 were diagnosed by LSIL cytology results (PPV evaluated for fine-needle aspiration cytology (FNAC) in parathyroid tis-
71.42%) and finally 6 cases had ASCUS cytology results (PPV 60%). sue and the corresponding specimen diagnosis.
The positivity of DS was more frequently expressing in HSIL lesions and Results: In total 12 samples were obtained pertaining to the re-
decreasing in LSIL lesions. ferred period. Out of these, in 3 (25%) the diagnosis of parathyroid
 Virchows Arch

tumour more suggestive of PA was made based on the cellularity, served as controls. Results were correlated with HPV-HR test
architectural patterns, nuclear morphology, immunocytochemistry (CEPHEID®), histological and cytological follow-up data.
and clinical data. The respective surgical resection specimens con- Results: Equivocal cytology concerned ASCUS (n=23), LSILs (n=11),
firmed the diagnosis of PA having a concordance of 100%. In the ASC-H (n=31) and AGCs (n=9). HSILs (n=44) and WNLs (n=31) served
remaining parathyroid samples, the diagnosis of parathyroid tissue as controls. Follow-up data was available for 145 patients: 63 histologies and
was rendered and no surgery was performed. 82 cervical smears. Sensitivity, specificity, PPV and NPV of p16/Ki 67+ for
Conclusion: Even though FNAC has its limitations in distinguish PA CIN2+ ASCUS was 66%, 85%, 40% and 100% for LSIL, it was 66%, 75%,
from other lesions, our results seem to show that it may have a role in not accessible, and 75%, for ASC-H it was 100%, 36,3%, 69,5% and 100%,
pre-operatory assessment, avoiding unnecessary overtreatment. and for HSILs it was 100%, 100%, 100% and 100%. Among AGCs one p16/
Ki67 negative smear showed CIN2 on biopsy and 4 had WNL cytology.
Among WNLs only one case was p 16/Ki67+ without follow-up data.
PS-14-021 In smears of women over 40, the interpretation of hyperchromatic crowded
A follow-up study on thyroid aspirates reports as follicular lesion of cell groups due to atrophy is often challenging. High sensitivity and speci-
undetermined significance (FLUS) in 2017: a retrospective study ficity of p16/Ki67 dual staining allows the detection of underlying CIN2+
with histopathological correlation even in equivocal and atrophic smears with ASCUS and ASC-H cytology.
Conclusion: Thanks to its good NPV p16/Ki67 dual staining represents
F. Ramalhosa1, A.C. Lai2, R. Almeida3,4, M.A. Cipriano5, R.C. Oliveira2, an excellent triage tool in patients with atrophic smears.
G. Fernandes2, M.J. Martins2 Keywords: CINtec®OLUS, ASCUS, LSIL, ASC-H.
1
Centro Hospitalar e Universitário de Coimbra, Portugal, 2 Centro
Hospitalar e Universitário de Coimbra, Portugal, 3 Centro Hospitalar e
Universitário de Coimbra - Pathology Department, Portugal, 4 Faculty of PS-14-023
Medicine in Coimbra, Portugal, 5 Centro Hospitalar e Universitário de P16/ki67 immunostaining in the triage of postmenopausal women
Coimbra - Pathology Department, Portugal with ASCUS and LSIL cytology Results:
A. Repse Fokter1, S. Šramek Zatler1, N. Irgel1, L. Salobir1, B. Antolovič1,
Background & Objectives: Thyroid fine-needle aspiration (FNA) is the D. Podgoršek1, A. Dovnik2
1
fastest and minimally invasive technique to tailor patients for surgery. The Department of Pathology and Cytology, Celje General Hospital,
thyroid nodules cytology is classified accordingly with The Bethesda Slovenia, 2 Department of Gynaecological Oncology and Oncology of
System for Reporting Thyroid Cytopathology (TBSRTC), revised in the Breast, University Clinical Centre Maribor, Slovenia
2017. Follicular lesion of undetermined significance (FLUS) is a hetero-
geneous category which includes cases for which the cytological findings Background & Objectives: Interpretation of postmenopausal smears
are not convincingly benign, with an implied malignancy risk of 5–15%. and gynaecological treatment of these patients can often be difficult and
The objective was to review cytology and histopathology reports, clinical time consuming. The objective of this study was to assess the perfor-
and ultrasound data, for thyroid nodules reported as FLUS, in order to mance of p16/Ki-67 dual-stained cytology as a triage of ASCUS and
evaluate the malignancy rate and to assess factors associated with malig- LSIL cytology results in postmenopausal women.
nant outcome. Methods: All consecutive ASCUS and LSIL smears in one-year period
Methods: A retrospective study of 2.174 FLUS, at Centro Hospitalar e were collected and p16/Ki-67 immunostaining was performed retrospec-
Universitário de Coimbra, was performed to compare with the second tively. The results were compared with histology results or long-term
FNA cytology and to relate with histological and imaging findings (the type cytology follow-up in cases with no biopsy.
of carcinoma and nodule size), in order to estimate malignancy predictors. Results: Among 269 cases in the study there were 239 (88.5%) with
Results: The overall incidence of FLUS in 2017 was 8.9% (191/ ASCUS and 30 (11.5%) with LSIL diagnosis. Dual p16/Ki67 staining
2.174);19(20.9%) were referred to surgery and 134(70.15%) were was positive in 18 (8%) and 6 (20%) of ASCUS and LSIL patients,
followed-up by repeat FNA, in a period of 7-12months. respectively (chi-square=5.100; p=0.024). Out of 24 patients with posi-
After the second FNA, a benign result was found in 84 patients (62.7%) tive p16/Ki67 staining, 14 (58.3%) had HSIL detected on subsequent
and 50(37,3%) had category equal or higher than grade III [22.4% follow-up. Out of 245 patients with negative p16/Ki67 staining, 235
FLUS/III and 14,9% IV-VI]. Forty-nine patients underwent surgery (95.9%) had low grade/normal histology or normal follow-up (chi-
(25.7%) and of these:15 cases (31.3%) had a malignant disease: 84,2% square=101.074; p<0.001).
papillary thyroid carcinoma and 29(64.4%) had benign lesions. Conclusion: Dual p16/Ki67 staining is a useful additional method in
Conclusion: The risk of malignancy in FLUS in our study is in accor- postmenopausal patients with low grade cytology.
dance with the estimated by TBSRTC. Second FNA following a FLUS
diagnosis is useful for better classification since the majority of FLUS are
benign. PS-14-024
Cyto-hystologic correlation in anal samples. Two years experience
J.M. Suárez Gómez1, A. Lopez Janeiro1, A. Rodriguez Garcia1, E. Senda
PS-14-022 Gorta1, M.J. Beato Merino1, P. Lopez Ferrer1 and B. Vicandi Plaza1
1
Utility of the p16/Ki67 dual stain in equivocal Liquid Based Cervical Hospital Universitario La Paz, Spain
Cytology (LBC) in everyday practice
H.E. Razafindrafara1, E. Pacevicius1, A. Mendibourg1, S. Blaise1, P. Le Background & Objectives: Anal Intraepithelial Neoplasia (AIN) is a pre-
Van Quyen1, G. Lang-Averous1 cancerous condition that can be detected with cytology. We aimed to exam-
1
University Hospital Strasbourg, France ine the correlation between cytological findings and biopsy diagnosis.
Methods: We selected cases from our center of patients undergoing anal
Background & Objectives: The aim of this study was to evaluate the cytology and posterior anal biopsy during the years 2016 and 2017. From
utility of p16/Ki67 dual staining (CINtec®PLUS) in equivocal cytology, 1503 anal cytologies consulted, 239 met inclusion criteria. We recorded
to identify CIN 2+ in everyday practice. cytological and biopsy diagnoses, Human Papilloma Virus (HPV) status,
Methods: This retrospective study included equivocal cervical (BD and gender. We determined prevalence of cytological and biopsy lesions,
SurePath®) LBCs of 149 women with a mean age of 43,8 years that were concordance between them, HPV infection prevalence, as well as sensitivity
dual stained for p16/Ki67 between 2015 and 2018. HSILs and WNLs and specificity of anal cytology. Analysis was performed using R (3.5.2).
Virchows Arch

Results: We analysed 239 patients, 91% were male, 40% were infected Background & Objectives: To assess the biocompatibility and bio-
by HPV 16, 10% were infected by HPV 18, and 88.5% were infected by degradation of porous, bioengineered collagen matrices (hemostatic
other types. There were no differences between the prevalences of HPV collagen sponge and iGen) in case of subconjunctival and
infection among sexes. In our study, 13% of cytologies and 27% of intrascleral implantation.
biopsies were negative. High grade lesions represented 4% and 30% of Methods: 32 eyes of 16 adult rabbits underwent translimbal
all cytological and biopsy diagnoses respectively. Prevalence of concor- microdrainage. Group 1 included 16 eyes of 8 adult rabbits with
dance between cytological and biopsy diagnosis was poor (Weighted hemostatic collagen sponge implanted subconjunctivally and
Kappa =0.19). Sensitivity and specificity of cytology in relation with intrasclerally. Group 2 included 16 eyes of 8 adult rabbits with
biopsy lesion was 89.3% and 21.5% respectively. iGen subconjunctival and intrascleral insertion. Rabbits were
Conclusion: Anal cytology is sensible for the detection of precancer- sacrificed on day 7, 30, 60, 90. Enucleated eyes were fixed in
ous lesions, especially in high-grade lesions, and less specific in 10% formaldehyde and stained with methylene blue and fuchsine
ASCUS and LSIL. Our results suggest that cytological and biopsy for general histological observation. Morphometric analysis of con-
diagnostic categories are non-overlapping. In literature, when period- junctiva, sclera and matrix was performed.
ic sampling can be done, it increases sensibility. The high prevalence Results: Hemostatic collagen sponge and iGen showed good bio-
of HPV infection in our population limits its clinical utility as a risk compatibility as subconjunctival and intrascleral implants. The bio-
stratifier. degradation rate of both materials was higher in scleral tunnel than
under conjunctival flap. Hemostatic collagen sponge had resolved
by 60 days, iGen - by 30 days. Strong negative correlation between
PS-14-025 angiogenesis and extracellular matrix fibrosis in both groups during
Squamous cell carcinoma metastasis in pleural and pericardial the whole period was revealed. The decrease of conjunctival and
effusions scleral angiogenesis was noted on day 90 in group 1, on day 60 in
E. Sunnetcioglu1, C. Aydin2, O. Hurdogan1, D. Yilmazbayhan1, P. Firat2, group 2.
Y. Ozluk1 Conclusion: Hemostatic collagen sponge and iGen are biocompati-
1
Istanbul University, Istanbul Faculty of Medicine, Department of ble for conjunctiva and sclera. The longer period of angiogenesis in
Pathology, Turkey, 2 Koc University Hospital, Department of case of hemostatic collagen sponge implantation decreases the risk
Pathology, Turkey of subconjunctival and scleral scar formation following glaucoma
surgery.
Background & Objectives: Squamous cell carcinoma (SqCC) is rare-
ly diagnosed in effusion cytology. In this study, we aimed to docu-
ment effusion samples diagnosed as SqCC and evaluate the efficacy PS-15-002
of p16 immunostaining for determination of the primary site. The use of hemostatic collagen sponge as a matrix for tissue bioengi-
Methods: We retrospectively reviewed archive records of two medi- neering: animal model of full-thickness bulbar conjunctivalesion
cal centers for pleural and pericardial effusions diagnosed as SqCC T. Demura1, N. Fisenko2, E. Kogan1
1
between 2009-2018. Clinicopathological features were retrieved First Moscow State Medical University (Sechenov University), Russia,
2
from the pathology reports and hospital database. Eighteen cases Research Institute of Eye Diseases, Russia
with adequate cell blocks were included. We performed p16 immu-
nohistochemical stain on cell blocks. Cutoff level for positivity was Background & Objectives: To study the healing processes of full-
90% diffuse, nuclear or nuclear and cytoplasmic staining. thickness wounds in the adult rabbit conjunctiva after grafting
Results: There were 16 pleural and 2 pericardial effusions. Male to with hemostatic collagen sponge (a porous biodegradable matrix
female ratio was 3.5:1 with a mean age of 63.5 (range 38-85) comprising collagen (98%), boric acid (1.25%) and furacilinum
years. The primary sites were lung (10), uterine cervix (2), head (0.75%).
and neck (1), oesophagus (1), and larynx (1). Three cases were of Methods: A 6-mm trephine was used to create a full-thickness lesion of
unknown primary. Out of 13 cases with poorly differentiated mor- bulbar conjunctiva. Wounds were grafted with hemostatic collagen
phology, 5 (1 lung, 1 uterine cervix, and 2 unknown origin) sponge (right eyes of 10 rabbits) or remained ungrafted (left eyes of 10
showed signet-ring like appearance. All cases showed positivity rabbits). Rabbits were sacrificed on day 7, 15, 21, 30. Enucleated eyes
with at least one of the squamous cell markers (p63, p40). P16 were fixed in 10% formaldehyde and stained with hematoxylin-eosin.
positivity was observed in only 2 patients with a previous history The healing of conjunctiva was evaluated by immunohistochemistry
of cervical cancer. and scanning electron microscopy. The expression of TGFβ, αSMA,
Conclusion: SqCC in effusion cytology poses diagnostic difficulties, VEGF in the wound was scored from 0.5 to 6.
especially due to variations in histomorphological appearance. Albeit Results: Biodegradation of hemostatic collagen sponge passed from
low number of cases, our case series show that p16 immunostaining periphery to the center of the wound. By 30 days collagen sponge had
can be an efficient diagnostic marker for HPV-induced uterine cervical degraded and grafted wounds had closed with conjunctival stroma
cancer metastases. Further studies in larger number of series are needed to and stratified squamous epithelium. Moderate (4) expression of
confirm our finding. VEGF, αSMA expression and low (2) level of TGFβ reflected this
process. By 30 days, ungrafted wounds had closed by contraction and
formation of fibrous tissue covered with stratified squamous epithe-
Tuesday, 10 September 2019, 09:30 - 10:30, Agora 3 lium. VEGF, αSMA expression was equal to 0.5, TGFβ expression
PS-15 | Ophthalmic Pathology was moderate (4).
Conclusion: Hemostatic collagen sponge serves as a scaffold for cell
migration and proliferation and can promote the formation of nearly nor-
PS-15-001 mal conjunctiva in case of full-thickness wounds.
Biodegradable collagen matrix as a subconjunctival and intrascleral
implant: an animal model
T. Demura1, N. Fisenko2, E. Kogan1 Tuesday, 10 September 2019, 09:30 - 10:30, Agora 3
1
First Moscow State Medical University (Sechenov University), Russia, PS-16 | Paediatric and Perinatal Pathology
2
Research Institute of Eye Diseases, Russia
 Virchows Arch

PS-16-001 neoplasm with worse prognostic, like yolk sac tumour or other sex
Expression of Sox2 and its regulation in the cells of residual respira- cord-stromal tumours. The clinical context may be useful. However,
tory epithelium in foetal pulmonary aplasia certain cases may present histological findings that may pose a
A. Apostolou1, M. Joubert2, C. Piolat1, B. Poreau1, P. Jouk1, C. Coutton1, diagnsotic challenge.
F. Arbez Gindre3, E. Brambilla1, H. Sartelet1
1
CHU Grenoble, France, 2 CHU Nantes, France, 3 CHU Besançon,
France PS-16-003
Liver mesenchymal hamartoma, a report of a case
Background & Objectives: Pulmonary agenesis is defined by a total A. Bdioui Thabet1, C. Pierre2, H. Busby2, N. Mhammedi2
1
absence of bronchi, pulmonary parenchyma and pulmonary vessels. Georges Pompidou Hospital Paris France, 2 Brabois Hospital, Nancy,
Normal embryonic lung development is the result of a complex France
reciprocal induction between the endoderm and mesoderm involv-
ing proteins and transcription factors, in particular SOX 2. The Background & Objectives: Mesenchymal hamartoma of the liver is a
regulation of SOX 2 is essential for the morphogenesis of the benign tumour of infancy characterised by an admixture of epithelial
bronchial tree. The main objective of this work is to study the structures in a loose connective tissue stroma with fluid accumulation
expression of SOX 2 in the residual respiratory epithelium of pul- suggestive of lymphangiomatous channels. The differential diagnosis in-
monary agenesis/aplasia. cludes other paediatric hepatic masses, in particularly hepatoblastoma.
Methods: Six cases of pulmonary agenesia/aplasia aged between 12 and Methods: A 9-month–old female infant, with history of incidentally dis-
25 week of gestation and 6 controle cases age matched of normal foetal covering of intra-abdominal large anechoic cyst, during antenatal ultra-
bronchi, trachea and oesophagus were studied. An immunohistochemical sound. Postnatal examination of the baby revealed a palpable cystic mass
study was performed using primary antibodies against SOX2, BMP4, in the right hypochondrium. No other congenital abnormalities were not-
FGF9, FGF10, TTF1, Shh et Bcatenin. ed. A computed tomographic scan similarly showed a large complex
Results: The residual epithelium presents a high expression of Sox 2 multiloculated cystic. Laparotomy was performed at 2 months. The
and an absence of expression of BMP4 while in control cases, there is lésion was removed with a clear margin.
an absence of expression Sox 2 and a expression of BMP4. The Results: In gross, the lesion measure 12 cm, having numerous cysts, each
squamous epithelium of the oesophagus presents a high nuclear ex- approximately 4 to 7 cm in size, containing clear fluid.
pression of Sox 2 and an absence of expression of BMP4. No differ- The histopathology showed solid areas mixed with multiloculated cysts.
ences between our control cases and our pathological cases The solid areas consist of loose myxoid stroma containing dilated ducts
concerning the expression of FGF 9, FGF10, SHH, TTF1 and lined by cuboidal epithelium. The cysts are surrounded by a layer of loose
βcatenin. mesenchyme without an identifiable epithelial lining and appear to be
Conclusion: The presente study observed a continuous expression Sox 2 bounded by the mesenchyme itself. The child is well on follow-up with
associated with an absence of BMP4 in epithelium of bronchi or trachea a normal appearing liver.
bud in agenesis and pulmonary aplasia at different gestational ages. Thus, Conclusion: Hepatic mesenchymal hamartoma is a benign tumour that is
BMP4 seems regulate tissue specific proliferation activity during lung typically diagnosed in childhood; its etiology has not been completely
development. elucidated. Complications of an enlarging hepatic mesenchymal
hamartoma stem from compression of adjacent vital organs and struc-
tures. Prognosis is excellent with complete resection.
PS-16-002
Testicular juvenile granulosa cell tumour: a case report in a newborn
L. Barona García1, B. Ferri Ñíguez2, M.I. Oviedo Ramírez1, A. Salazar PS-16-006
Nicolas1, M.I. Ortuño Moreno1, A. Caballero Illanes1, E. Martínez Gorham-Stout disease: a French series
Barba1 S. Boudjemaa1, J. Donadieu2, S. Fraitag3, E. Angot4, H. Sartelet5, S.
1
Servicio de Anatomía Patológica. Hospital Clínico Universitario Virgen Valamary-Degano6, I. Pommepuy7, G. Leverger2, S. Heritier2
de la Arrixaca., Spain, 2 Hospital Clínico Universitario Virgen de la 1
Sorbonne Université- APHP6, Hôpital Armand Trousseau, Service
Arrixaca, Spain d'Anatomie et Cytologie Pathologiques, Paris, France, 2 Hôpital
Armand Trousseau, France, 3 Enfants Malades Necker Hospital, France,
4
Background & Objectives: Neonate 10 days age with an enlarged CHU de Rouen, France, 5 CHU de Grenoble, France, 6 CHU de
descended right testis, smooth and firm to palpation. There was no other Besançon, France, 7 CHU de Limoges, France
abnormalities on physical exam. Alpha-fetoprotein was slightly in-
creased. Scrotal ultrasound revealed a multicystic mass with internal vas- Background & Objectives: Gorham Stout disease (GSD) is a rare idio-
cular flow that replaced the testicle. The patient underwent a right radical pathic disorder with about 200 reported cases in children and adults. GSD
inguinal orchiectomy without complications. is characterised by spontaneous and progressive osteolysis of one or more
Methods: Gross pathologic examination revealed a 2.2 × 1.5 × 1.0 cen- skeletal bones, related to proliferation of thin-walled vascular channels.
timeter gray–white ovoid mass with multiple cysts containing light yel- Typical radiographic finding is represented by intramedullary and sub-
low glistening fluid. cortical radiolucency, hence the name of “phantom bone” or “vanishing
Results: Histologically there were variably shaped and sized follicles bone disease”.
lined by bland- looking oval to round cells arranged in single and multiple Methods: We retrospectively reviewed 13 GDS cases collected over a
layers, with basophilic fluid in the lumen. The stroma was fibrous with 28-year period (1990-2018).
bland spindle cells positive for actine around the follicles. Tumour cells Results: There is a male predominance (10 males and 3 females, sex ratio
showed positive immunoreactivity for inhibin, WT1 and calretinin, while 3,3). Patient age varied from 1 month to 18 years (median age 7.9 years). As
negative for panCK, alpha-fetoprotein (AFP), CD30, CD117, PLAP, D2- reported in the literature, maxillofacial involvement represented about 30%
40 and OCT3/4. Diagnosis of Juvenile granulosa cell tumour (JGCT) was in our series (5/13). Other locations included: 2 vertebral, 2 costal, 2 mul-
made. tifocal, 1 peritoneal and 1 unknown. Clinical manifestations were variable,
Conclusion: Even though JGCT is the most common testicular tu- but the more frequently reported were bone pain and local swelling.
mour in infants < 6 months, there are few cases described in the Histological diagnosis was usually challenging, showing nonspecific vas-
literature. Its importance lies in the differential diagnosis with other cular proliferation intermixed with fibrous connective tissue and
Virchows Arch

sometimes inflammatory component in bones or adjacent soft tissues. In Methods: We report a well-documented case of Candida glabrata
some cases, fibrous tissue completely replaced resorbed bone, without chorioamnionitis that occurred in second trimester pregnancy and result-
vascular proliferation. On immunohistochemistry, D2-40 was usually ed in foetal loss.
expressed with variable expression of vascular markers. Results: A 24-year-old woman, gravida 2, para 0, with a history of premature
Pathogenesis of GSD is still unknown and up to now, no somatic muta- rupture of membranes in the second trimester due to a probable fungal infec-
tion that could drive this vascular abnormality has been highlighted. tion, was referred to our Institution because of the recurrence of premature
The best therapeutic management is undefined and patients frequently rupture of membranes. She delivered a non-macerated female foetus at 17
received bisphosphonate therapy, and/or sirolimus or interferon alpha weeks gestation. At autopsy, examination of the stillborn revealed normal
therapy. growth and didn’t demonstrate any malformation. The placenta weighed
Conclusion: Multidisciplinary discussion based on clinical, radiological 84g (normal ranges: 120-135g) and histological examination of the foetal
and histological criteria is key in establishing this usually challenging membranes showed a severe polymorphic inflammatory infiltrate and large
diagnosis. fungal colonies of yeast-like microorganisms which stained positively with
periodic acid-Schiff. The histological features in conjunction with the positive
vaginal cultures enabled to identify Candida glabrata as the etiologic agent of
PS-16-008 the severe chorioamnionitis.
Foetal mediastinal teratoma: misinterpretation as congenital cystic Conclusion: Although Candida glabrata has been considered saprophyte
lesions of the lung on prenatal diagnosis of the normal vaginal flora and only pathogenic in pregnancies with
S. Darouich1, N. Taamallah2, H. Bellamine3 history of vitro fertilization or cervical cerclage, it can cause
1
Unitè de Pathologie Foetale et Placentaire, CHU Habib Bougatfa, chorioamniotits in healthy woman with no clear risk factors.
Universitè de Tunis El Manar, Facultè de Mèdecine de Tunis,
LR99ES10 Laboratoire de Gènètique Humaine, Tunis, Tunisia,
2
Clinique Raouabi, Tunisia, 3 Service d'Anatomie et Cytologie PS-16-010
Pathologiques, Hôpital Menzel Bourguiba, Tunisia Hepatic phenotypes of HNF1B mutations: a foetal case of renal cysts
and diabetes syndrome and literature review
Background & Objectives: Teratomas are among the most common S. Darouich1, H. Bellamine2
1
congenital tumours and frequently reported to be associated with foetal Unitè de Pathologie Foetale et Placentaire, CHU Habib Bougatfa,
hydrops. The thoracic teratomas are commonly misinterpreted on prena- Universitè de Tunis El Manar, Facultè de Mèdecine de Tunis,
tal ultrasound, being confused with congenital adenomatoid malforma- LR99ES10 Laboratoire de Gènètique Humaine, Tunis, Tunisia,
2
tion of the lungs, diaphragmatic hernia or bronchopulmonary sequestra- Service d'Anatomie et Cytologie Pathologiques, Hôpital Menzel
tion. The aim of this case report is to document this challenge. Bourguiba, Tunisia
Methods: In the present case, we correlated prenatal diagnosis with au-
topsy findings of mediastinal teratoma complicated by severe hydrops Background & Objectives: Hepatocyte nuclear factor 1-β (HNF1B)
foetalis. defects cause renal cysts and diabetes syndrome (RCAD syndrome),
Results: The ultrasound revealed severe hydrops foetalis, but little is known on liver pathology in patients. We aim to illustrate
placentomegaly and multiple pulmonary cysts that were suggestive of the most severe hepatic phenotype of HNF1B mutation in a fetus present-
cystic adenomatoid malformation of lung. Autopsy of the 24-weeks ges- ing with RCAD syndrome with review of the literature.
tation stillborn male foetus showed a 54.3g, 6.1 x 4.4 x 2.8-cm, large and Methods: We described the autopsy findings in a female foetus present-
well encapsulated polycystic mediastinal teratoma with thymic, cardiac ing with RCAD syndrome with a special focus on the liver abnormalities.
and pulmonary hypoplasia, and moderate post-hemorrhagic hydrocepha- Results: Pregnancy was terminated in a 28-year-old woman because of
lus. Histological study confirmed that the tumeral mass was consistent plymalformative syndrome at 20 weeks gestation. Macroscopic examina-
with immature teratoma and revealed placental diffuse chorangiomatosis tion showed foetal hypotrophy, facial dysmorphism, hypoplastic
and chorangiosis. Perineum, lower limb amyotrophy, major pancreatic hypoplasia, bilateral
Conclusion: This case emphasizes that congenital mediastinal teratoma nephromegaly with moderate pelvicalyceal dilation, hepatomegaly with
should be considered in the differential diagnosis of non-immune multiple large subcapsular cysts, short gut, heart-shaped uterus and severe
hydrops, particularly if a thoracic cystic lesion is detected on ultrasonog- enlargement of lateral ventricles. Histological examination demonstrated
raphy. bilateral renal medullary cysts and hepatic periportal fibrosis, and con-
firmed the presence of multiple subcapsular liver cysts that appeared to be
lined by a cuboidal or squamous epithelium. A review of the previously
PS-16-009 published foetal and paediatric cases with well-documented liver histol-
Candida glabrata chorioamniotitis: a cause of premature rupture of ogy allowed distinguishing various hepatic lesions associated with
membranes and foetal loss without identifiable risk factors HNF1β defect including paucity or proliferation of the bile ducts, severe
S. Darouich1, H. Bellamine2 biliary stasis, mild to severe periportal fibrosis and extramedullary hema-
1
Unitè de Pathologie Foetale et Placentaire, CHU Habib Bougatfa, topoiesis. Subcapsular hepatic cysts were not previously reported.
Universitè de Tunis El Manar, Facultè de Mèdecine de Tunis, Conclusion: Our study demonstrates that the histological liver lesions
LR99ES10 Laboratoire de Gènètique Humaine, Tunis, Tunisia, associated with HNF1B mutations are of variable severity. The document-
2
Service d'Anatomie et Cytologie Pathologiques, Hôpital Menzel ed foetal case is the most severe hepatic phenotype. There is, however, no
Bourguiba, Tunisia clear genotype‐phenotype correlation.

Background & Objectives: Chorioamnionitis is a major cause of pre-

mature rupture of membranes and foetal loss. It commonly results from an PS-16-011
ascending bacterial or fungal infection. Candida glabrata is the second Hydrops foetalis associated with Wolf-Hirschhorn syndrome and
most common commensal yeast of the vagina, the pathogenicity of which large foam cells on bone marrow: a fortuitous association with lyso-
is limited in healthy hosts. It is reported to be associated with somal storage disorder
chorioamnionitis in pregnancies with history of in vitro fertilization or S. Darouich1, I. Lariani2, M. Kharrat2
1
cervical cerclage. We aim to show that Candida glabrata chorioamnionitis Unitè de Pathologie Foetale et Placentaire, CHU Habib Bougatfa,
may occur in pregnancy without any identifiable risk factor. Universitè de Tunis El Manar, Facultè de Mèdecine de Tunis,
 Virchows Arch

LR99ES10 Laboratoire de Gènètique Humaine, Tunis, Tunisia, showed a very thin diaphragm which was strikingly elevated into the
2
Universitè de Tunis El Manar, Facultè de Mèdecine de Tunis, thoracic cavity. The intercostal muscles were also markedly thinner than
LR99ES10 Laboratoire de Gènètique Humaine, Tunis, Tunisia normal. The lungs were severely hypoplastic with a combined weight of
only 12.35g (expected for dates 26.8, lung weight/body weight ratio
Background & Objectives: Hydrops foetalis has a wide range of possi- 0.006). The Neuropathological examination was normal.
ble etiologies, providing a diagnostic challenge for the physician. It may Microscopically, the skeletal muscle showed dystrophic rearrangements
be a presentation of the lysosomal storage disorders including including small muscle fibers with centrally placed nuclei resembling
mucopolysaccharidosis VII and IVA, type 2 Gaucher disease and infantile foetal myotubes, large areas of muscule degeneration and abundant
sialic acid storage disease. Thus, all cases of unexplained hydrops foetalis endomysium. The severe alterations in the dystrophic skeletal muscles
should be investigated for these disorders by histological and biochemical without involvement of the central nervous system were suggestive of
or molecular methods in order to provide the family with an appropriate mutation in LAMA2-gene. Molecular analysis was considered.
genetic counselling. We document a challenging case of non-immune Conclusion: This case report emphasizes that diaphragm eventration can
hydrops foetalis associated with 4p deletion be the manifestation of an underlying muscular or neuromuscular disor-
Methods: We described pertinent autopsy findings that were consistent der. Therefore, examination of the central nervous system and muscle
with a lysosomal storage disorder in a hydropic fetus and discussed the tissues is necessary in any neonatal death due to unexplained respiratory
available genetic test results. distress.
Results: Prenatal ultrasound detected hydrops foetalis in a 38-year-old
woman at 17 weeks gestation. Amniocentesis was performed. The preg-
nancy was terminated and subsequent autopsy was performed. The male PS-16-013
fetus weighed 77.35 g with a crown to heel length of 16 cm and foot Cystic teratoma of the face - report of a rare case
length of 1.6 cm, which were consistent with a gestational age of 15-16 S. Foreid1, J.M. Dias1
1
weeks. He presented with ankyloglossia, hypospadias, club feet, subcu- Synlab Pathology Porto, Portugal
taneous edema, ascites and pericardial and pleural effusions. The liver
weight was in normal range. There were no heart defects. The lengths of Background & Objectives: Teratomas are among the most common
the long bones were consistent with 13-14 weeks gestation. The placenta germ cell tumours in children. These are true neoplasm’s composed of
was not received. On histological examination, multiple and large storage tissues derived from the three blastodermic layers (ectoderm, mesoderm
cells, involving the chondrocytes and osteoclasts, were found in bone and endoderm), that are capable of independent growth in tissues foreign
marrow. The cells were filled with abundant closely packed small vacu- to the body part in which they arise.
oles which were weakly stained positive for PAS. In the other foetal The most frequent locations are the sacrococcygeal region and gonads.
tissues, similar vacuolized cells could not be identified. Karyotype Extragonadal sites are less frequent. Presentation in the neck and head
showed partial deletion of the short arm of chromosome 4 with chromo- area is exceptionally rare, representing 2-5% of all cases (2). Here we
somal formula 46 XY,del(4)(p14;pter). Mucopolysaccharidosis type IVA present a case of a facial teratoma in a 4 year old children.
was suspected. The NGS-based sequencing and copy number variation Methods: This case is about a 4 year old children with a cystic mass in the
analysis did not detect any mutation or deletion/duplication of the face. By image exams, a diagnosis of lymphangioma was made. Surgery
GALNS and GLB1 genes. Whole exome sequencing was considered. was not recommended, instead, the aspiration of the cystic contents for
Conclusion: Diagnosis of hydrops foetalis that cannot be explained by a management. After the first aspiration, the cyst grew back in a couple
chromosomal aberration should encourage the pathologist to search for months. Because at this time there was facial disfigurement and a concern
storage cells in the foetal tissues, especially the bone marrow. Further that the facial nerve could be affected, surgery was done.
biochemical and genetic investigations, that have impact on genetic Results: The gross specimen measured 5x4, 5 x 3,5cm. The cut section
counselling and prenatal diagnosis, may then be considered. revealed a biloculated cyst, with a macroscopic appearance resembling an
intestinal bowel loop.
Microscopic examination revealed that the cyst wall was composed of
PS-16-012 structures similar to the ones found in the intestinal wall.
Congenital eventration of the diaphragm due to early-onset muscular Immunostains with CDX-2, CD10, Chromogranin, synaptophysin,
dystrophy: an unusual cause of neonatal respiratory distress cytokeratinAE1/AE3, smooth muscle actin, desmin, protein S100 and
S. Darouich1, H. Bellamine2 calretinin stained the same structures expected in a normal intestinal wall.
1
Unitè de Pathologie Foetale et Placentaire, CHU Habib Bougatfa, Conclusion: Because of its rare location, teratomas of the face are often
Universitè de Tunis El Manar, Facultè de Mèdecine de Tunis, misdiagnosed as lymphangiomas and cystic hygromas, when they are
LR99ES10 Laboratoire de Gènètique Humaine, Tunis, Tunisia, predominantly cystic. Definitive diagnosis usually cannot be confirmed
2
Service d'Anatomie et Cytologie Pathologiques, Hôpital Menzel until the histopathologic analysis of the specimen. Needle aspiration may
Bourguiba, Tunisia provide temporary relief, but does not represent a definitive measure
given the propensity for recurrence, and surgery should be considered.
Background & Objectives: Congenital diaphragm eventration is a de- In our case, we document the presence of mature tissue derived from all
velopmental abnormality characterised by hypoplasia of the diaphragm three germ layers allowing us to make the diagnosis of teratoma.
due to severe early-onset muscular dystrophy. It may result in lung hypo- Unlike adults, most teratomas presenting in early childhood are congen-
plasia and neonatal respiratory distress. We aim to illustrate such a case. ital and benign, rarely turning malignant. The histopathological examina-
Methods: We described the autopsy findings of a female newborn dying tion in our case had shown only mature tissue components, with no
from respiratory failure due to congenital muscular dystrophy related evidence of immature tissue or malignant transformation, compatible
diaphragm eventration. with a benign nature.
Results: This female infant was born to a 26-year-old G3P2 woman.
Pregnancy was complicated by polyhydramnios. Premature rupture of
membranes occurred at 35 weeks gestation with subsequent vaginal de- PS-16-014
livery of a 1931.55g girl with body length of 44cm and head circumfer- Foetal autopsy unveiling the death: a rare congenital central nervous
ence of 32cm. The newborn was hypotonic and made no spontaneous system neoplasia
breathing movements. She died after 15 min of resuscitative efforts. On J. Fraga1, A. Lai1, C. Cerdeira1, M. Silva2, A. Alarcão2, O. Rebelo1, R.
physical examination, she had club feet. Gross autopsy examination Pina1, L. Carvalho1,2
Virchows Arch

1
Centro Hospitalar e Universitário de Coimbra, Portugal, 2 Faculdade de Results: Four cases of fatal neonatal candidiasis have been identified
Medicina da Universidade de Coimbra, Portugal between 2014 and 2019. Median gestational age was 27 weeks. All
mothers presented spontaneous rupture of membranes and abnormal vag-
Background & Objectives: Glioma is the leading Central Nervous inal discharge. Median weight of the infants was 900g. One infant was
System (CNS) tumour in children. Low-grade gliomas are the leading stillborn and the other 3 died after 3-8 days due to candidemia, with
paediatric CNS tumours overall and responsible for 1/3 of cases. Higher respiratory arrest and multiorgan failure. Histopathological examination
grade gliomas occur less often (7–11 %) of cases of CNS malignancy revealed angioinvasive hyphae in the lung (n=4), brain (n=2), liver (n=3),
beyond infancy. spleen (n=2), kidney (n=2) and gastrointestinal tract (n=3).
Methods: We present a medical pregnancy termination at 37 weeks of Conclusion: Preterm infants are predisposed to Candida infections main-
gestational age, of a female foetus, due to cerebral hemorrhage and hy- ly due to the immaturity of their immune system. Congenital candidiasis
drocephalus (normal anterior echography). is rare and must be distinguished from other conditions presenting with
Results: Autopsy revealed asymmetric brain with 345g. In section, there pustular lesions at birth. Central venous catheterisation and parenteral
was a left, paramedian nodular formation with 4.3x3.8cm, with extensive nutrition are significant risk factors for developing candidemia, which
hemorrhage appearance, friable, located in the frontal lobe with extension can be fatal or lead to severe complications with lifelong repercussions.
to the corpus callosum, leading to deviation of the midline structures. It
corresponded to a glial neoplasia with hemorrhagic necrosis, with
hypercellular areas consisting of cells of clear, ill-defined cytoplasm, PS-16-017
nuclear atypia and rare mitosis. Immunohistochemistry study showed PD-L1 and PD-L2 mutations in paediatric Hodgkin Lymphoma: do
positivity of tumour cells for GFAP and WT1 and negativity to IDH1, they have any prognostic significance?
OLIG2, MAP2, synaptophysin, EMA, p53 or H3K27M. Genetic evalu- G. Gul1, D. Ince2, N. Olgun2, E. Özer3
1
ation demonstrated absence of EGFR and IDH mutations and 1p/19q Tepecik Training and Research Hospital, Department of Pathology,
codelection. Izmir, Turkey, 2 Dokuz Eylul University Faculty of Medicine
Conclusion: Autopsy diagnosed an unpredicted congenital CNS neopla- Department of Paediatric Oncology, Turkey, 3 Dokuz Eylul University
sia: diffuse astrocytoma, IDH-wild type, without mutations in the IDH Faculty of Medicine Department of Pathology, Turkey
genes: a rare neoplasia that most likely constitute a variety of entities which
can follow a broad range of clinical courses and could be reclassified in Background & Objectives: Reed-Sternberg cells are able to escape from
adults as other tumours with additional genetic analyses. Astrocytoma is the the immune system by multiple mechanisms including the enhancement
commonest glial tumour of infancy and childhood, frequently outside the of the expression of programmed cell death-1 ligands (PD-L1 and PD-
posterior fossa and typically as an intracranial mass and it tends to causing L2). We aimed to investigate PD-L1 and PD-L2 gene mutations in child-
hydrocephalus, macrocephaly and intracranial hemorrhage. hood Hodgkin Lymphoma's (HL) and their relationships with clinical and
prognostic parameters.
Methods: The study included 39 paediatric HL patients treated with a
PS-16-015 standard protocol. PD-L1 and PD-L2 mutations were determined by
Neonatal mortality due to congenital candidiasis in low birth weight whole exome Sanger sequencing. Clinicopathological parameters includ-
infants: a 5-year retrospective study from an Emergency Unit in ing age, sex, histological subtype, bone marrow and lymph nodes with
Romania involvement, clinical stage, bulky disease, EBER positivity, LDH level,
T.A. Georgescu1, A.C. Lisievici2, S. Barbu3, V.A. Dumitru3,4, R. erythrocyte sedimentation rate and event-free survival were obtained
Bohiltea5,6, M. Costache7,4, M. Sajin8,9 from patients’ records. Statistical analyses were performed to address
1
Department of Pathology, Bucharest Emergency University Hospital, the relationship between mutation profile and both clinical and patholog-
Romania, 2 Carol Davila University of Medicine and Pharmacy, ical variables.
Bucharest, Romania, 3 Department of Pathology, "Carol Davila" Results: Eight cases (20,5%) showed p.R260C mutations, and three
University of Medicine and Pharmacy Bucharest, Romania, (7,7%) pR234L in the exome 5 of PD-L1 gene. None of the cases had
4
Department of Pathology, Emergency University Hospital Bucharest, PD-L2 mutations. In statistical analysis, p.R260C mutation exhibited a
Romania, 5 Department of Obstetrics and Gynaecology, "Carol Davila" significant relationship with older age and nodular sclerosing (NS) histo-
University of Medicine and Pharmacy Bucharest, Romania, 6 Department logical type (P=0.04 and P=0.04, respectively). PD-L1 mutation did not
of Obstetrics and Gynaecology, Emergency University Hospital statistically correlate with other variables.
Bucharest, Romania, 7 Department of Pathology, "Carol Davila" Conclusion: Although PD-L1 mutation did not show statistically signif-
University of Medicine and Pharmacy, Bucharest, Romania, 8 SUUB, icance with well-established prognostic factors, based on our findings
Romania, 9 UMF Carol Davila, Romania indicating significance with NS histology and older age, we speculate
that PD-L1 gene mutations may be associated with better prognosis in
Background & Objectives: Congenital candidiasis is an extremely rare paediatric HL. This conclusion can be explained by amino acid sequence
and severe cause of early-onset sepsis, usually caused by an ascending change affecting the PD1 / PD-L1 interaction, and thereby preventing
infection from the maternal genital tract. The condition manifests within malignant cells from escaping the immune system.
the first few days of life and involves a high mortality rate (35%). It may
be localized (congenital cutaneous candidiasis), presenting as an exten- Our study was funded by Turkish Paediatric Oncology Group Society
sive skin rash which eventually results in widespread desquamation, or (TPOG) research project support.
generalized (congenital systemic candidiasis), resulting in respiratory dis-
tress, meningitis, sepsis and death.
Methods: In this 5-year retrospective study developed within the PS-16-018
Pathology Department of the Emergency University Hospital Bucharest Morphometric analysis of vascular clefts in children with symptoms
Romania, we aim to evaluate the clinical and histopathological aspects of of acute appendicitis and negative appendectomy
fatal candidiasis in infants and correlate the results with literature data. We B. Jurić1, M. Kirigin1, R. Ivelj2, A. Čizmić2, I. Pezelj3, B. Krušlin1,4
1
reviewed slides from foetal autopsies and extracted clinical information Department of Pathology and Cytology, Sestre Milosrdnice University
from archived medical files. Cases confirmed by culture in Sabouraud Hospital Center, Croatia, 2 Children's Hospital Zagreb, Croatia, 3 Clinic of
agar were selected. Additional Periodic acid-Schiff and Grocott's methe- Urology, Sestre Milosrdnice University Hospital Center, Croatia,
4
namine silver stains were performed from archived tissue blocks. School of Medicine, University of Zagreb, Croatia
 Virchows Arch

Background & Objectives: Acute appendicitis is one of the most components of WT were negative with PDGFR-alfa. The other cases
common causes of abdominal emergency surgical procedures. showed variable positivity.
Many cases of clinically suspected acute appendicitis showed no Conclusion: Cyclin D1 is not a specific immunohistochemical marker
microscopic signs of acute inflammation. Negative appendectomy due to its strong and diffuse positivity in CCS cases. It may be useful to
rate differs greatly, partly due to various criteria different differentiate CCS from blastemal and stromal components of WT.
Institutions use to define acute appendicitis. Prominent vascular Staining patterns of PTEN, beta-catenin and PDGFR-alfa indicate the
clefts, frequently found in negative appendectomy specimens, tumours using these pathways. Other markers except cyclin D1 do not
could be implicated in the pathophysiology of acute appendicitis have a role in differential diagnosis.
and might be one of the early signs of inflammation.
Methods: We conducted a retrospective study by searching for
patients who had negative appendectomy at Children's Hospital PS-16-020
Zagreb (January 1st 2014-March 31st 2019). 124 patients were Angiogenesis and apoptosis in human placentas with aneuploidies -
identified, aged 1-18. Their histologic slides were re-examined. trisomies 21, 18 and 13
Vascular clefts, if present, were measured microscopically. Other A. Kolobov1, V. Karev2, O. Kolobova3
1
abnormalities were also noted, such as the presence of fecaliths. Saint Petersburg University, Russia, 2 Children's Scientific and Clinical
Statistical analysis was carried out. Center of Infectious Diseases, Saint Petersburg, Russia, 3 Saint Petersburg
Results: Out of the 124 patients included in the study, 50,8% were Paediatric Medical University, Russia
female (n=63), and 49,2% were male (n=61). Mean age of pa-
tients was 11,5 and median was 12 years. 94 of 124 (75,8%) Background & Objectives: Trisomies 21, 18 and 13 are the fre-
negative appendectomy specimens showed prominent vascular quent aneuploidies in live newborns. The aims of this study were
clefts. Vascular clefts width varied between 140 and 1751 μm. to compare CD31, bFGF and FasL expressions in placentas with
12 specimens (9,7%) showed no signs of vascular clefts, and 18 normal and trisomic karyotype and to associate differentially
specimens had partial vascular clefts which did not penetrate the expressed with concrete biological pathways.
muscular wall of the appendix and consequently could not be Methods: The placentas were collected from four groups of patients: 1)
measured. 63,7% (n=79) of appendices contained fecaliths in their placentas from foetuses of gestation 19-21 weeks with trisomy 21 (10
lumina. placentas); 2) placentas from foetuses of gestation 19-21 weeks with
Conclusion: Our results suggest that widened vascular clefts as sites of trisomy 18 (10 placentas); 3) placentas from foetuses of gestation 19-21
weakness in the muscular layer of the appendiceal wall may be one of the weeks with trisomy 13 (10 placentas); 4) placentas from foetuses of
first signs of acute appendicitis. gestation 19-21 weeks without any congenital defects and abnormal kar-
yotype (control group – 20 placentas). CD31, bFGF and FasL expression
was studied immunohistochemically.
PS-16-019 Results: In placentas with trisomy 21 the expression CD31 was 1.52
Role of immunohistochemistry on differential diagnosis of paediatric ±0.54% (in control group – 6.8±1.54%, p<0.05); the expression bFGF
renal tumours: expression of Cyclin D1, PTEN, PDGFR-alfa and was 11.27±1.75% (in control group – 3.28±0.26%, p<0.01). In placentas
Beta-catenin with trisomy 13 the expression CD31 was 2.7±0.84%. The expression
Z. Ecem Kain1, G. Gokturk Ozcan1, R. Ozcan2, S. Emre2, T. Tiraje FasL in group with trisomy 21 (1.22±0.77%) and trisomy 13 (0.16
Celkan2, N. Comunoglu2 ±0.08%) in comparison with control group (4.43±0.79%) statistically
1
Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, significant decreased. The expression of FasL was the highest in placentas
Pathology, 2 Istanbul University-Cerrahpasa, Cerrahpasa Faculty of from foetuses with trisomy 18 (11.74±0.09%).
Medicine, Department of Paediatric Surgery, Istanbul, Turkey Conclusion: Thus, in placentas with trisomies 21 and 13 is disturbance of
branching and vascularization of villi. In placentas with trisomy 18 the
Background & Objectives: Paediatric renal tumours overlap activation of apoptosis is noted.
histomorphologically, and may cause misdiagnosis. Blastemal compo-
nent of Wilms tumour (WT) may mimic clear cell sarcoma (CCS) and
Ewing sarcoma, while stromal component of WT mimics CCS and PS-16-021
mesoblastic nephroma (MN). Recent studies suggest several immunohis- 9-years-old male with isolated mucormycosis of trachea and
tochemical markers to differentiate between these overlapping features. In bronches: a case report
this study, we aimed to determine the role of immunohistochemical stain- N. Korchagina1, T. Vorozhbieva2, E. Tumanova3, D. Zhakota3
1
ing patterns of Cyclin D1, PTEN, beta-catenin and PDGFR alfa, on pae- N.F. Filatov Children's City Hospital of Moscow Healthcare Ministry,
diatric renal tumours. Russia, 2 Moscow City Oncology Hospital №62, Russia, 3 Pirogov
Methods: A total of 34 paediatric and 2 adult renal tumours (16 Wilms Russian National Research Medical University, Russia
Tumour,10 clear cell sarcoma, 2 congenital mezoblastic nephroma
(CMN),3 cellular mesoblastic nephroma (CeMN),2 rhabdoid tumours Background & Objectives: We report the case of isolated mucormycosis
(RT), 1 solitary fibrous tumour (SFT),1 Ewing sarcoma (ES),1 diffuse of trachea and bronches of 9-year-old patient with diabetes for 1 month.
large B-cell lymphoma (DLBCL)) cases were included in the study. Four Mucormicosis is a rare complication of diabetes mellitus, which usually
blocks of paraffin tissue microarray were constructed. Cyclin D1, PTEN, occurs with long-term experience of this disease.
beta-catenin and PDGFR-alfa were performed on all cases. Staining in- Results: 9-year-old male with diabetes for 1 month came to the our clinic
tensity was graded from weak to strong, the extensity was graded as with complaints of cough, dyspnea. On the same day, there was a drop SaO2
percentages. to 60%, respiratory arrest, after resuscitation vital functions were restored. In
Results: All cases of CCS and epithelial components of WT showed bronchoscopy in the lower third of the trachea is black, the lumen is narrowed
positivity for Cyclin D1 but blastemal and stromal components of WT by 50%, with fibrinous overlay, and granulations. Lumen of right main bron-
were negative. All cases of CCS and CMN, and most cases of WT chus was spot, covered with floating portion of the right wall of the trachea.
consisting of blastemal and stromal components demonstrated loss of During the study, the material was taken for histological examination.
expression with PTEN. Most cases of CCS and all components of WT The biopsy spicement consisted on the necrotic tissue with non-septate
showed cytoplasmic, weak staining with beta-catenin,while rhabdoid hyphae branching at wide angles, that allowed to conclude about the
components showed strong positivity. ES, CMN, and rhabdoid presence of the patient mucormycosis. The patient's condition was
Virchows Arch

progressive deterioration, respiratory failure was increased, necrotic Democritus University of Thrace, Greece, 5 Histology-Embryology
changes in the trachea were progressed, which required VA-ECMO and Lab., Medical Department, Aristotle University of Thessaloniki,
traditional lung ventilation. Despite the ongoing therapy, the patient died Greece, 6 Physiology Lab., Medical Department, Democritus University
on the 20 day of his stay in the clinic. of Thrace, Greece
The autopsy confirmed an isolated mucormycosis of the lower third of the
trachea and the main bronchi, thrombosis of the pulmonary arteries. Background & Objectives: Pre-eclampsia is a particularly serious dis-
Conclusion: We found only 5 articles in the last 50 years with similar order expressed during pregnancy, which is usually expressed in the
pathology in Scopus and RSCI databases. All of these cases was in the clinical triptoma: proteinuria, hypertension, edema. The endocannabinoid
elder patient with minimal 5-years experience of the diabetes mellitus and receptor CB1 is known to be a G protein that acts in synergy with delta-9-
episodes of ketoacidosis. tetrahydrocannabinol (THC), which is the major psychoactive agent of
cannabis. We aimed to assess the expression of CB1 endocannabinoid
receptor in histological placental samples with a characteristic pre-
PS-16-022 eclampsia disorder during foetal development.
Segmental absence of intestinal musculature in infant with Methods: Forty (40) samples from pre-eclamptic placentas as well as
Hirschprung disease normal ones were used. We performed indirect immunohistochemistry
B. Krsteska1, B. Ilievski2, L. Spasevska3, V. Janevska3, P. Zdravkovski2, using anti-CB1 antibody. Immunohistochemical staining was evaluated
V. Stojkovski 2 , V. Naunova 4 , V. Filipovski 5 , M. Bogdanovska- using a Nikon Eclipse 50i optical microscope and antibody expression
Todorovska2, G. Petrushevska3 was graded with a semi-quantitatively four scale scoring system (0-3).
1
Institute of Pathology, Medical Faculty, Republic of North Macedonia, 2 Results: Τhe results demonstrated increased expression of the CB1 receptor
Institute of Pathology, Medical faculty, Skopje, Republic of North in pathological samples relative to normal ones. Preeclamptic women over
Macedonia, 3 Institute of Pathology, Medical Faculty, Skopje, Republic the age of 35, as well as those in higher gestational weeks had higher levels of
of North Macedonia, 4 University Clinic for Paediatric Surgery, Skopje, receptor expression. It is also demonstrated that pre-eclampsia is an indepen-
Republic of North Macedonia, 5 Acibadem Sistina Hospital, Laboratory dent factor that correlates directly with high levels of CB1 expression. In
for Histopathology and Cytology, Skopje, Republic of North Macedonia contrast, low levels of CB1 expression were observed in normal placentas.
Conclusion: To conclude, increased expression of the CB1 receptor ap-
Background & Objectives: Segmental absence of intestinal musculature pears to correlate with the pathogenesis of preeclampsia. Eventually, the
(SAIM) is a rare histopathologic entity with a few published cases in receptor could be considered a valuable prognostic marker when it comes
neonatal pathology and has uncertain pathogenesis. It is classified as to this disorder. However, it is always proposed to review the hypotheses
primary congenital or secondary acquired. Clinical manifestations usually and outcomes of this research work, as well as to elucidate the underlying
are intestinal obstruction and perforation. Majority of reported cases are reasons and mechanisms that lead to these outcomes.
neonates, children, but it can affect adults also.
Methods: We present a case of male, 6 months old baby, with previ-
ously diagnosed Hirschprung disease when multiple colorectal biop- PS-16-024
sies were taken and colostomy was made. After 1 month he develops Molecular investigation and identification of apoptotic and inflam-
fever and vomits with poor clinic evolution. Intraoperativelly there matory factors involved in normal and abnormal pregnancies
was diffuse peritonitis and intestinal adhesions due to perforation. A M. Lambropoulou1, T. Deftereou1, S. Tologkos1, V. Papadatou1, I.
75cm long segment of small intestine was resected. The wall of in- Koukourakis1, C. Alexiadi1, P. Tsikouras2, T. Alexiadis1, G. Tripsianis3,
testine was thinned (paper-like) with massive hemorrhage and peri- O. Pagonopoulou4, M. Simopoulou5, N. Papadopoulos1
1
tonitis. Many specimens were taken for pathohistologic analysis Histology-Embryology Lab., Medical Department, Democritus
along the whole length of the intestinal segment. The tissue sections University of Thrace, Greece, 2 Obstetrics & Gynaecology Dep.,
were formalin fixed and paraffin embedded and routinely stained Medical Department, Democritus University of Thrace, Greece,
3
with HE. Additional immunohistochemical analysis was performed Medical Statistics Lab., Medical Department, Democritus University
with SMA. of Thrace, Greece, 4 Physiology Lab., Medical Department, Democritus
Results: All specimens revealed absence of intestinal muscular layer with University of Thrace, Greece, 5 Physiology Lab., School of Medicine
intact mucosa, muscularis mucosae, submucosa and serosa. There was National & Kapodistrian University of Athens, Greece
transmural diffuse acute inflammatory infiltrate and hemorrhage with
fibrinopurulent peritonitis. Immunohistochemically SMA confirms the ab- Background & Objectives: The aim of this study was to evaluate apo-
sence of muscularis propria and marks muscularis mucosae. Resection of ptosis in placentas coming from pathological and normal pregnancies, as
the affected segment is curative. Up to now the baby is in good condition. well as inflammation and viral infections markers expression. Furthermore,
Conclusion: There is no published case of SAIM associated with we tried to uncover a possible link between the level of apoptosis and
Hirschprung disease. As etiopathogenesis remains unclear and there is a inflammation, the outcome of the pregnancy and viral presence.
spectrum of published histopathologic morphologic elements there is a Methods: We examined 68 placentas from pathological pregnancies and
need of homogenous classification for further comparative studies. 24 from normal pregnancies. Immunohistochemistry was applied to ana-
lyse apoptotic expression using M30 and TUNEL method, whereas anti-
bodies against TNF-a and NF-kβ were used for inflammation detection.
PS-16-023 Furthermore, we used anti-CMV and anti-HSV antibodies to evaluate viral
Possible involvement of endocannabinoid receptor CB1 expression in presence. Antibodies expression was graded in terms of the proportion of
the pathogenesis of preeclampsia: immunohistochemical study positively stained cells according to a semi-quantitatively four scale scoring
M. Lambropoulou1, E. Karantzali2, V. Papadatou1, M. Simopoulou3, S. system (0-3).
Tologkos 1 , T. Deftereou 1 , T. Alexiadis 1 , S. Alexopoulou 2 , I. Results: Our analysis showed that inflammation and apoptosis markers
Koukourakis1, G. Tripsianis4, S. Meditskou5, O. Pagonopoulou6 were found in higher expression patterns in the study group compared
1
Histology-Embryology Lab., Medical Department, Democritus with the control group with statistical significance. Regarding the viral
University of Thrace, Greece, 2 Histology-Embryology Lab. Medical infection, only 10 positive cases were found, all among patients with
Department, Democritus University of Thrace, Greece, 3 Physiology adverse pregnancy outcomes. Furthermore, when we focused in the study
Lab., School of Medicine National & Kapodistrian University of group, all the markers showed a statistically significant correlation be-
Athens, Greece, 4 Medical Statistics Lab., Medical Department, tween high expression and increased mother’s age as well as higher
 Virchows Arch

gestational weeks. Moreover, the presence of viral infections has also (c.706dupG + c.706dupG) that codifies for a truncated protein
been correlated with higher inflammation and apoptosis levels. (p.Glu236Glyfs*5 + p.Glu236Glyfs*5). Autopsy findings revealed
Conclusion: Our results established a clear correlation between adverse a prominent forehead, flat nasal bridge, malformed ears, intrauter-
pregnancy outcomes, viral placental infection and higher inflammation ine growth retardation, as well as polycystic kidneys and steatosis
and apoptosis levels. However, the underlying mechanisms involved in in the liver, confirming the diagnosis of glutaric aciduria type II.
these procedures need further clarification. Conclusion: The foetal autopsy allowed the characterisation of the
novel variant (c.706dupG at ETDFH) as pathogenic. Genotype-
phenotype relationship is important in the study of rare genetic
PS-16-025 disorders such as glutaric aciduria type II, as variants are usually
Paediatric diffuse myocardial fibrosis: a case report familiar-specific leading to a difficulty in the characterisation of
C. Makni1, M. Ksentini1, N. Zneidi Sabbegh1, Z. Ghorbel1, R. Aloui1, I. their pathogenicity.
Boubaker1, A. Trahore1, A. Blel1, H. El Mokh1, I. Ben Romdhane1, L.
Hadj Kacem1, M. Ben Khelil2, M. Hamdoun2, S. Rommani Rammeh1
1
Pathology Department, Charles Nicole Hospital, Tunisia, 2 Forensic PS-16-027
Medicine Department, Charles Nicole Hospital, Tunisia Infantile-onset lysosomal acid lipase deficiency
O. Mishnev1, A. Talalaev1,2, L. Leonova1,2, Y. Semina2
1
Background & Objectives: Etiologies of myocardial fibrosis vary ac- Pirogov Russian National Research Medical University (RNRMU),
cording to age, medical history, clinical presentation and histological Russia, 2 Morozovskaya Children's Clinical Hospital, Russia
findings. The aim of this case report is to discuss the etiologies of diffuse
myocardial fibrosis among paediatric population. Background & Objectives: Lysosomal acid lipase deficiency (LAL-
Methods: We present a rare case of diffuse myocardial fibrosis resulting D), Wolman disease is a rare autosomal recessive lysosomal stor-
in a child’s sudden death. age disease characterised by progressive accumulation of choles-
Results: An 8-year-old boy was victim of a sudden death while at school. terol esters and triglycerides in the liver, spleen and other. The
He had no known personal medical history or family history of sudden goal is to show the importance of genetic expertise for clinical
death at a young age. Necropsy findings revealed slightly hypertrophic and full autopsy diagnosis of LAL-D.
myocardium, with pale and fibrous appearance. All the other organs were Methods: LAL-D was diagnosed in two full-term sisters from the same
congestive without other abnormalities. Histological examination re- family, who died at the age of two months and three months respectively.
vealed an important hypertrophy of myocardial fibers in both right and Similar clinical manifestations of the disease were rapidly progressing in
left ventricles associated with fibrosis of the interstitial tissue. There was the sibs from birth, complicated by viral and bacterial infections and led to
no significant myocardial fibers disorganization, nor inflammatory reac- the death caused by multiple organ failure. Intravital molecular genetic
tion. Pulmonary non inflammatory alveolar edema was noticed, as well as and morphological expertise of the autopsy material was carried out using
lesions of chronic hepatitis. Toxicological tests were reported negative. basic histological methods with hematoxylin-eosin, Pas-reaction and
Myocardial fibrosis is rare in paediatric population. The etiologies can be Masson’s trichrome stain.
divided in two groups: chronic heart failures occurring on congenital Results: Clinically: appetite decrease, hypotrophy, reflexes decrease,
cardiac malformations and those occurring on structurally normal hearts. hepatosplenomegaly, jaundice, dyslipidemia, hypoalbuminemia, increase
The pathologies occurring on a structurally normal heart can be either in blood acid phosphatase, coagulopathy, anasarca. The activity of LAL
primary cardiomyopathy (dilated, hypertrophic or restrictive) or second- was reduced. Molecular genetic research has revealed compound-
ary (arythmogenic, ischemic, toxic, infiltrative or infectious). In view of heterozygote c.442del & c.817_818del. Specific enzyme replacement
the association with the hepatic lesions, we concluded that myocardial biological therapy with Kanuma (Sebelipase alpha) was carried out with-
fibrosis would be probably secondary to myocarditis. No virological in- out effect. The autopsy research revealed typical LAL-D changes:
vestigations were done. microvesicular steatosis with the outcome of micronodular liver cirrhosis,
Conclusion: Diffuse myocardial fibrosis is rare in paediatric population. lipids and calcifications in the adrenal glands, accumulation of lipids in
Histological examination establish the diagnosis and can help in the eti- lymph nodes and intestine mucosa.
ological orientation. Conclusion: Classic LAL-D diagnostic is based on typical clinical
and morphological symptoms: reduction of the LAL activity, ele-
vated blood acid phosphatase levels and histological findings of
PS-16-026 microvesicular steatosis on liver tissue, accumulation of lipids in
Utility of foetal autopsy for the characterisation of Glutaric Aciduria internal organs and calcifications in the adrenal glands. Molecular
type II genetic expertise of the child and his parents is key method of
A.P. Martinez Aracil1, A. Perez-Rodriguez1, I. Llano-Rivas2, A. Sagasta1 successful diagnosis of the disease.
1
OSI Araba University Hospital, Spain, 2 Genètica Clinica- Servicio de
Genetica, Hospital Universitario Cruces, Biocruces-Vizcaya Health
Research Institute, Spain PS-16-028
Shwachman-Diamond Syndrome in a child of 11 months
Background & Objectives: Glutaric aciduria is a rare and lethal disorder O. Mishnev1, A. Talalaev1,2, L. Leonova1,2, Y. Semina2
1
that affects metabolism of fatty acids. Lipid accumulation is observed in Pirogov Russian National Research Medical University (RNRMU),
the tissues. Enlarged, polycystic kidneys and hepatomegaly with steatosis Russia, 2 Morozovskaya Children's Clinical Hospital, Russia
are common findings and can be prenatally detected. Therefore we
wanted to pathologically and genetically characterise a foetus of 15 Background & Objectives: Shwachman-Diamond syndrome (SDS),
weeks, from a consanguineous couple, carrier of a novel ETFDH variant, or Shwachman–Bodian–Diamond syndrome, is a rare congenital
with 4 previous perinatal deaths. multisystemic disorder characterised by exocrine pancreatic insuf-
Methods: Due to the medical history, prenatal echography and a chorial ficiency, bone marrow dysfunction with aplasia or leukemic trans-
biopsy for ETDFH-associated glutaric aciduria analysis was ordered. The formation, skeletal dysplasia and abnormalities. The syndrome was
gestation was interrupted and the foetal autopsy performed. named for doctors Harry Shwachman and Lois Diamond (1964).
Results: Sanger sequencing confirmed the presence of the homo- The goal is to show the importance of genetic expertise for clinical
zygous familiar probably pathogenic variant in the ETFDH gene and complete pathologic diagnosis of SDS.
Virchows Arch

Methods: Invitrial molecular genetic research and morphological exam- Background & Objectives: Abernethy syndrome is an eponym for con-
ination of the autopsy material was conducted for a full-term child who genital extrahepatic portocaval shunt. It can be divided in two types
died 11 months old, using hematoxylin-eosin and immunohistochemical depending if liver is perfused (type II: partial shunt) or not (type I: total
reactions with monoclonal antibodies such as Insulin, Glucagon and CD shunt) with portal blood. It is a rare condition and causing
15. Since birth, the clinical manifestations of the disease were progressing hepatopulmonary syndrome is even rarer. Here, we present a suspect case
rapidly and led to the death caused by bacterial infection. in an autopsy of a male child with 19 months old.
Results: The blood test revealed: neutropenia, anemia, thrombocytope- Methods: Imagiologic studies in the context of acute respiratory distress
nia. By Sanger’s method of sequencing the gene SBDS (ex 1-5): raised the suspicion of an extrahepatic portocaval shunt. The patient died
c.201A>G (p=), genotype A/G (rs1061695) was detected. An autopsy and to verify the cause of death and to confirm the extrahepatic shunt, an
examination revealed: pancreatic lipomatosis, chronic inactive pancreati- autopsy was performed using the Letulle (en mass) method to preserve
tis, fatty degeneration of the liver and single myeloid and granulocyte the vascular supply and relationships between organs. The block of tho-
cells in the bone marrow, nesidiodysplasia, cortical dysplasia of the kid- racic and abdominal organs was immersed in formalin and evaluated after
neys and a cleft of the soft palate was revealed. Immunohistochemically: fixation. Samples for histologic evaluation were collected.
positive reactions with Insulin, Glucagon; lack of the reaction in the bone Results: The autopsy showed that the main causes of death were recent
marrow with CD 15. myocardial infarct, acute lobar bronchopneumonia, diffuse alveolar le-
Conclusion: The peculiarity of the observation was the defect of the sion and hemorrhagic diathesis. Hypoplasia of portal vein was verified,
exocrine and endocrine pancreas and kidney dysplasia. The child’s dis- together with intra-abdominal, intrahepatic and also pulmonary vascular
ease was quickly progressing with febrile fever, steatorrhea, the loss of malformations. Chronic effects of the partial portal shunt were also found
appetite, hepatosplenomegaly, hypotrophy, necrosis of soft tissues of face like oesophageal varices, severe pulmonary hypertension and cor
and extremities. Molecular genetic expertise of the child and his parents is pulmonale.
a key to a successful diagnosis of the disease. Conclusion: The Abernethy type II malformation was confirmed and
caused in this child an hepatopulmonary syndrome, along others vascular
malformations, promoting a cascade of events that lead to death.
PS-16-029
High-grade foetal vascular malperfusion is associated with diffuse
chorionic haemosiderosis PS-16-031
E. Mooney1, E. Crotty1, M. Culliton1 Wilms' tumour arising from nephrogenic rests located inside a tubu-
1
National Maternity Hospital, Ireland lar colon duplication adherent to the kidney: an exceptional case
C. Picard1, G. Schneider1,2, J. Pracros1,3, S. Collardeau-Frachon1,4, P.
Background & Objectives: Diffuse chorionic haemosiderosis (DCH) is Leblond5,6, F. Hameury1,2, F. Dijoud1,4
1
an abnormality of the placental membranes, characterised by the deposi- Hospices Civils de Lyon, France, 2 Dèpartement de chirurgie viscèrale
tion of iron pigment. It is usually secondary to recurrent venous bleeding pèdiatrique, France, 3 Service d'imagerie mèdicale, France, 4 Institute de
from early pregnancy. In many papers, it is associated with pre-term Pathologie Multisite, France, 5 Institute d'Hèmatologie et de Cancèrologie
delivery. Foetal vascular malperfusion (FVM) is an abnormality of the Pèdiatrique, France, 6 Service de cancèrologie pèdiatrique, France
fetoplacental circulation that may be seen at any gestational age, but often
in the third trimester. No link has been identified in the placental literature, Background & Objectives: Colonic duplication is the less common
but we have noted the two conditions co-existing. This study examined reported congenital duplication of the gastrointestinal tract and is
the association of these two entities. characterised by multiple clinical presentations. Renal adhesion of a du-
Methods: Laboratory records were searched for singleton cases diag- plication at an early stage may induce the infiltration of the digestive wall
nosed as DCH on H&E stain over a 5 year period. These were classified by embryonic nephrogenic tissue, which could give rise to neoplasia.
as showing high-grade FVM (HGFVM), low-grade FVM (LGFVM) or Methods: This 2-year old child without significant medical history was
no FVM. Controls were gestational-matched cases without DCH. Cord referred to the emergency for mild abdominal bloating and fever. Imaging
length, coiling, insertion, or other abnormalities were noted. Membranes found a tubular communicating sigmoid colon duplication, ending in a
were classified as normal or circumvallate. Results were analysed using retroperitoneal extra-renal and extra-adrenal cystic calcified collection,
Graphpad. thought to be part of the malformation. Pre-operative procedures 2
Results: There were 66 cases of DCH between 16 and 41 weeks gestation months later showed a growing palpable colon duplication.
and 130 controls. 14/66 (21%) cases of DCH showed HGFVM and 2/66 Results: Surgery found the duplication ending in a large cystic mass,
(3%) showed LGFVM. 16/130 (12%) controls showed HGFVM and 20/ adherent to the upper pole of kidney. Cyst rupture during surgical manip-
130 (15%) had LGFVM. Where FVM is present, high-grade FVM is ulation revealed a suspect tissue, compatible with a Wilms’ tumour (WT)
significantly associated with DCH versus controls (P<0.0031 Fischer’s in frozen section. The duplication resection was completed by a left ne-
Test). phrectomy. Final histological examination confirmed the diagnosis of
Conclusion: HGFVM occurs significantly more often in placentas with WT. Colonic wall of the duplication end was infiltrated by immature
DCH. Histologic correlates of FVM have been under-explored to date. glomeruli associated with islands of blastema evocative of nephrogenic
We have previously shown that FVM occurs four times more commonly rests (NRs) that were continuous with the malignant tumour.
in placentas with maternal vascular malperfusion (MVM) (Cooley et al Conclusion: We report a case of WT arising from diffuse NRs located
JOG 2011). Both FVM and DCH are among 9 lesions significantly in- inside a colon sigmoid duplication adjacent to the kidney in a child. This
creased in placentas from infants with neurologic injury, and both are exceptional case demonstrates the potential of heterotopic NRs to evolve
independently related to neurologic injury (Redline & ORiordan Arch into primary WT. The adhesion between the digestive duplication and the
Pathol Lab Med 2000). Whether iron in high quantities causes or contrib- kidney may have taken place at an early stage of embryogenesis in this
utes to vascular damage in the developing placenta requires further study. child.

PS-16-030 PS-16-034
Abernethy syndrome - a case report Extravillous trophoblast peculiarities in pregnancies under circula-
C. Padrao1, A. M. G. Pereira1, F. Galante Pereira1, R. Theias Manso1 tory hypoxia conditions
1
Hospital Prof. Doutor Fernando Fonseca, EPE, Portugal O. Reshetnikova1, L. Rudiuk2,3
 Virchows Arch

1
Immanuel Kant Baltic Federal University, Russia, 2 Immanuel Kant chorion villi with zones of fibrinoid ‘glued’ villi and ischemic infarcts.
Baltic Federal University, Kaliningrad, Russia, 3 Regional Clinical Placental membrane thickness increased as a result of increased connective
Hospital of the Kaliningrad Region, Kaliningrad, Russia tissue and syncytiotrophoblast VF, smaller number of the capillaries per
villi. Foetal vessels mainly located within the central area of villi. It also
Background & Objectives: Pregnancy, complicated with circulatory contributed to the increase of the distance between maternal and foetal
hypoxia may cause placental dysfunction, which results in immediate blood circulations. General architecture of thyroid glands in late abortions
and lifelong consequences for a mother and child. Failures in adapting group followed the pattern similar to controls. Connective tissue fascicles
blood flow in mother-placenta-fetus system under congenital heart dis- between follicles were wider than in controls and VF of follicles clusters
ease (CHD) conditions can have a negative impact in oxygen and nutrient were smaller. The foci of immature structural units of the thyroid gland
transport to the developing fetus. Placental extravillous trophoblast occupied wider zones, divided with loose, poorly cellular, fibrous stroma.
(PEVT) is associated with immune and hormonal interactions in feto- Conclusion: Placental structural and functional disorder may cause thy-
placental complex. roid grand growth and maturation restriction.
The aim of present study was to evaluate the PEVT peculiarities in cases,
when pregnancy was complicated with CHD and when surgical interven-
tion preceded pregnancy. PS-16-036
Methods: Morphological study of 54 placentas was carried out according Retrospective analysis of the mortality rate in children with cystic
to the standard scheme. They were divided into groups: I - 20 cases of fibrosis in the industrial region of Donbas
CHD non-operated, II - 19 cases of CHD operated and 15 cases of phys- O. Reshetnikova1, E. Burgelo2, O. Teleshova2
1
iological pregnancy (control group). Histological slides, stained with he- Immanuel Kant Baltic Federal University, Russia, 2 Saint Luka Lugansk
matoxylin and eosin, were studied microscopically, then they were State Medical University, Lugansk, Lugansk People's Republic, Ukraine
analysed by point count method and using the computer morphometry.
The immunohistochemical staining protocol with monoclonal mouse an- Background & Objectives: Cystic fibrosis (CF) is a lethal genetic dis-
tibodies to SMA (Dako, 1:500) for placental tissue samples has been order caused by mutations in the transmembrane conductance regulator
developed. Morphological and immunohistochemical data were studied (CFTR) gene on chromosome 7. CFTR impaired function results in ab-
in parallel with clinical information. Differences between groups were normal ion transport at the apical membrane of airway epithelial cells
elucidated by non-parametric Mann-Whitney. Reliability established at which cause hyperviscous airway mucus formation. CF is variable in
p<0.05. clinical expressions, but lung disease is the major cause of mortality in
Results: Results have shown that PEVT volume fractions had no signif- patients with CF. Scientific data suggests that risk factors for lethal out-
icant differences in both CHD groups and controls. However, histological come of CF have different impact on individuals in countries of different
investigation of the first group placentas revealed PEVT cells dystrophy, income. Therefore the aim of the study was to investigate the information
cysts formation, accompanied with decreased SMA expression. about the mortality rate in children with cystic fibrosis in the industrial
Morphological peculiarities of the second group PEVT, as well as SMA region of Donbas, which for few years has suffered due to civilian mili-
expression were close to the control parameters. tary conflict.
Conclusion: Structural remodelling and immunohistochemical features Methods: 10 autopsy reports of children who died from CF and its com-
of PEVT are considered in the aspect of hormonal and immune adaptation plications for the period 2010-2018 have been studied. The diagnosis was
of placentas to circulatory hypoxia under CHD conditions in operated and made on the basis of clinical data, pathological and bacteriological exam-
non-operated patients. inations. The following indicators were also taken into account: age,
gender, type of bacterial infection, the form of CF and its complications.
According to the age of the child three groups were formed: I – 0 – up to 6
PS-16-035 months; II - 6 months- up to 1 year, III - 1 -3 years.
Placental pathology and foetal thyroid gland peculiarities in late Results: Results have shown that 50 % of CF lethal cases were
spontaneous abortions established in the 0-6 month’s age group. The minimal indicators were
O. Reshetnikova1, O. Zinchenko2, I. Goryanikova2 in the III group - 20%. No prevalence by gender was found. Most of the
1
Immanuel Kant Baltic Federal University, Russia, 2 Saint Luka Lugansk children had a mixed form of the disease and only one had an intestinal
State Medical University, Lugansk, Lugansk People's Republic, Ukraine form of CF. A microbiological study of the lung tissue revealed P.
Aeruginosa and Staphylococcus Aureus in majority of cases.
Background & Objectives: Adequate endocrine homeostasis within Conclusion: Late diagnosis and severe course of the disease, the devel-
foetus-placental system is crucial for normal child growth and develop- opment of purulent bronchopneumonia, multi organ failure syndrome led
ment. Placental pathology may influence in utero thyrogenesis and impair to the death of CF.
newborn thyroid function. Therefore, we investigated the association be-
tween placental morphology and thyroid histogenesis in cases, when
pregnancies terminated with late spontaneous abortions. PS-16-037
Methods: Thyroid gland of 38 foetuses from the late spontaneous abor- Maternal factors and foeto-placental peculiarities in cases of the
tions material were compared with 34 foetal glands in cases of induced IUGR
abortions due to psychological reasons (control group). Tissue samples O. Reshetnikova1, O. Kononenko2, A. Antonova2
1
were immersion-fixed in 10% buffered formalin solution, embedded in Immanuel Kant Baltic Federal University, Russia, 2 Saint Luka Lugansk
paraffin wax. Histological slides were stained routinely with hematoxylin State Medical University, Lugansk, Lugansk People's Republic, Ukraine
and eosin. Microscopical examination was performed on magnification x
10 and x 40. Morphometry of thyroid gland histology was conducted by Background & Objectives: Intrauterine growth restriction (IUGR) is an
point-count method. Volume fractions (VF) of pathological accumula- important reason of perinatal complications and high mortality.
tions, placental membrane components, etc. were revealed. All data were The aim of present study was to investigate maternal-foetal and placental
compared with control parameters. The differences were analysed with relationships in late gestation, as well as to establish possible imbalances
the help of Student’s t-test. in the development of the foetus and placenta.
Results: Results have shown morphological changes in placental structures Methods: 21 placentas from the late medical abortions at 20-22 weeks of
in cases from the late spontaneous abortions. The intervillous space had gestation (wg) due to psychotherapeutic reasons were divided in two
smaller VF due to fibrinoid accumulations, extremely close arrangement of groups: I – 11 cases of IUGR and II group (comparison) - 10 cases with
Virchows Arch

no foetal IUGR. The material of study included the results of a survey of frequency of their development differ in the Federal districts of the
women aimed at the medical termination of pregnancy. Foetuses and Russian Federation. Improving prenatal examination of the fetus is the
placentas were investigated at pathology department. Volume fractions main reserve for reducing mortality from congenital abnormalities.
(vf) of the major placental components were determined by computer Objective: to conduct a comparative analysis of congenital abnormalities
morphometry of H&E stained slides. The differences were analysed with frequency as the cause of stillbirth and early neonatal death in the Russian
the help of Student’s t-test. Federation.
Results: Results revealed feto -placental growth discordance in cases of Methods: The statistical analysis of Rosstat on the causes of stillbirth and
the IUGR. Placental-foetal ratio in the IUGR group increased to 0,42+ early neonatal death in the Russian Federation in 2012-2016 was
0,05 (II group -0,27+0,01,<0.01). The weights of the foetal liver, kidney, performed.
and heart were lower than in the II group. The relative indicators of the Perinatal losses were: 58298 stillbirths and 27367 early neonatal deaths.
foetal organs to the placentas weights were also lower in cases with Congenital abnormalities as the initial cause of death figured in 7846
IUGR. Poor placental vascularity and immaturity of the villous tree were cases (9,8%). They were the cause of stillbirth in 5.6% and early neonatal
common findings in IUGR cases. Placental membrane thickness here death in 16.8%.
increased compared with II group of investigation. In parallel terminal Results: Most often (39.3%), the causes of stillbirth were abnormalities
villi vessels occupied smaller area, while the area of the connective tissue from the “Other types of congenital abnormalities” group, which include
stroma increased. Patient’s survey showed that in the group I mothers multiple abnormalities. The second and third places were nervous system
were older, with lower educational level and more frequent drinking (25.7%) and heart (17.3%) congenital abnormalities, respectively.
alcohol. They were less involved in sports activity. Digestive system congenital abnormalities as the initial cause of death
Conclusion: On the basis of these results, it was estimated that maternal were the least common (2.9%). At early neonatal death, abnormalities
factors as well as inadequate remodelling of placental structures may from the “Other types of congenital abnormalities” group were also ob-
contribute to the development of clinical and morphological signs of served most often (44.2%). The heart (31.9%) and circulatory system
placental insufficiency and IUGR emergence. (7.7%) congenital abnormalities were second and third, respectively.
Conclusion: The type and frequency of lethal congenital abnormalities
detection differed in the Russian Federation Federal districts. The largest
PS-16-038 share of stillborn from congenital abnormalities was registered in the
Paediatric extragonadal germ cell tumours: a single center North-West Federal District (7.6%), and of early neonatal death - in the
experience Central Federal District (22.6%).
A. Sassi1, N. Boujelbene1, R. Doghri1, L. Charfi1, I. Abbes1, H. Houari1,
K. Mrad1, M. Driss1
1
Department of Pathology, Salah Azaiez Institute, Tunisia PS-16-040
Comparative characteristics of the villi vascularisation in
Background & Objectives: Extragonadal germ cell tumours (EGCT) are monochorionic diamniotic twin pregnancies with selective birth
uncommon paediatric tumours with particular clinical behaviour. Our aim weight discordance
is to report epidemiological, histopathological and prognosis characteris- A. Shchegolev1, U. Tumanova1, V. Lyapin1, V. Sakalo1, N. Тetruashvili1,
tics of EGCT. G. Sukhikh1
1
Methods: We performed a retrospective study of EGCT diagnosed at our NMRCOGP, Russia
department over a period of 20 years (1999–2019). Patients aged under
16 years old were included. Three age groups were defined with the Background & Objectives: Monochorionic twin gestations are associ-
following ranges: congenital/neonatal (birth-6 months), childhood/ ated with a high risk of poor pregnancy and perinatal outcome, including
prepubertal (7 months-12 years) and postpubertal (12 – 16 years). the development of foetal growth retardation.
Dermoid cysts were excluded. Objective: to study the degree of vascularization of the villi in
Results: A total of 30 patients were included. Mean age was 4.5 months monochorionic diamniotic twin placentas selective birth weight
(2 days – 11 years old). The congenital/neonatal group encompassed 57% discordance.
of patients and the childhood/prepubertal 43% of patients. There was a Methods: Complex morphological study of 12 placentas from
female predominance (63%). Specimen integrity was mainly intact monochorionic diamniotic twin placentas in selective birth weight discor-
(87%). The most common tumour site was sacrococcygeal (53%). dance was performed. Morphometric indices of terminal villi vasculari-
Tumour mean size was 9 cm and mean weight 250 gr. All EGCT were zation was determined on CD31 immunohistochemical preparations. The
teratomas of which 63% were mature. Immature teratomas were mostly area and perimeter of the terminal villi, as well as the number, area and
grade 3 (44%). Nonteratomatous components were not reported. For the perimeter of their capillaries were determined. Calculated the vasculari-
sacrococcygeal location, coccyx was not removed in 56% of the cases. zation degree indexes of villi (the ratio of the total area of the capillaries of
When removed, it was statistically associated with negative margins the villus to the cross-sectional area of corresponding villus).
(p=0.036). Results: The average weight of the larger newborn significantly exceeded
Conclusion: Sacrococcygeal teratomas are the leading paediatrician the weight of the smaller newborn (2167±131.4g vs 1626±194.6g, p<0,05).
EGCT. In these tumours, the presence of immature neuroglial elements At morphometric analysis of placenta preparations, the average area and
is not predictive of malignant behaviour. Coccygectomy has to be per- perimeter of terminal villi in the placenta of a foetus with a larger weight
formed for a complete surgical resection. Recurrence often occurs in the (2099.2±188.1mkm² and 168.1±8.5mkm) did not differ much from similar
form of a yolk sac tumour. indicators of the foetus with a lower weight (2081.4±93.2mkm² and 166.7
±3.6mkm). The average area and perimeter of terminal villi capillaries were
larger in the placenta of the foetus with less weight (85.0±7.8mkm² and
PS-16-039 33.7±1.5mkm vs 100.1±15.3mkm² and 35.9±2.4mkm).
Congenital abnormalities as a cause of perinatal death Conclusion: When studying microscopic specimens of monochorionic
A. Shchegolev1, U. Tumanova1, M. Shuvalova1, G. Sukhikh1 diamniotic twin placentas, different degree of the terminal villi vascular-
1
NMRCOGP, Russia ization were established depending on the weight of the foetus. The cal-
culated vascularization index of the terminal villi was higher in the pla-
Background & Objectives: Congenital abnormalities account for a sig- centa with a lower weight (36.2% vs 27.2%), which reflects the develop-
nificant proportion of the causes of perinatal death. The type and ment of compensatory processes in placental hypoxia.
 Virchows Arch

PS-16-041 the left - 1.4 times, and both lungs 1.3times, respectively. The highest
Features the glycome of syncytiotrophoblast in the placental terminal average volume of the thoracic cavity was observed in Group-I
villi during early-onset and late-onset foetal growth restriction (193.7ml), which exceeded Group-II by 1.06 times.
G. Kulikova1, M. Ziganshina1, A. Shchegolev1, V. Sinitsyna1, E. Conclusion: The ratio of right and left lungs in Group-I was 1.67, and in
Yarotskaya1, N. Kan1, V. Tyutyunnik1, G. Sukhikh1 Group-II - 1.37. The highest value of the specific volume of the lungs was
1
NMRCOGP, Russia in Group-II (58.4%) and exceeded the corresponding value in Group-I by
1.4 times.
Background & Objectives: Syncytiotrophoblast is an interface between
maternal blood and foetal extracellular fluid, responsible for hormone
production and nutrient exchange. Various molecular and functional PS-16-044
changes in syncytiotrophoblast are detected during pregnancy complica- Opportunities of postmortem MRI at autopsy for the diagnosis of
tions. Today there is limited data on syncytiotrophoblast glycopathology non-immune hydrops foetalis
in foetal growth restriction (FGR). The aim of the study was to charac- U. Tumanova1, V. Lyapin1, V. Bychenko1, A. Shchegolev1, G. Sukhikh1
1
terise the glycomе of syncytiotrophoblast in the placental terminal villi by NMRCOGP, Russia
lectin histochemistry in healthy women and in patients with early-onset
(EO) and late-onset (LO) FGR. Background & Objectives: With NHF, pathological fluid accumulations
Methods: Streptavidin-biotin-peroxidase labelling technique was used to was found in 2 or more cavities, THI-value in all studied areas indicates a
localize the binding sites for ten lectins (Con A, UEA-I, ECL, VVL, GSL- generalized edema of the skin, at our research.
I, GSL-II, MAL-II, SNA, SBA, DSL) in combination with enzymatic Objective: to identify and assess the severity of non-immune hydrops
treatments. Lectin binding patterns were analysed in 36 formalin-fixed foetalis (NHF) using postmortem MRI.
paraffin-embedded samples of placental tissues in early-onset FGR Group-I -7 died newborns from NHF; Group-II -7 died newborns with
(n=12), late-onset FGR (n=12) and normal pregnancy (n=12). signs of general edema syndrome in NHF absence; Group-III -10 dead
Quantitative analysis of histochemical reactions was performed by newborns with no signs of edema. 6-15hours after death, 3T MRI was
Nikon Eclipse E 80 computer program. The intensity of staining was performed before the autopsy.
assessed in 10 visual fields in each observation. Methods: The volume of fluid and its specific volume in serous cavities were
Results: Lectin-binding patterns of syncytiotrophoblast in FGR showed determined at 3D tomography reconstructions. The T1- and T2- signal inten-
increase of terminal residues of αGal-, αGalNAc- (GSL-I) and sity of the skin (T1siS, T2siS) in the body areas and fluid (T1siF, T2siF) were
sialoglycans with α (2,3)-linked sialic acids (MAL-II); and decrease of measured. The skin edema was determine by the formula of tissue hydration
mannose-containing glycans (ConA), compared to healthy patients. index (THI)=T2siS*T1siF/T1siS*T2siF*100.
Content of terminal Fucα- (UEA-I) was increased, and contents of termi- In Group-I hydrothorax was detected in 100%, ascites -in 85.7%,
nal Galβ- (ECL) residues and sialoglycans with α (2,6)-linked sialic acids hydropericardium -in 42.9%. In Group-II hydrothorax was in 57,1%,
(SNA) were decreased in EO FGR only. ascites -in 85.7%, hydropericardium -in 42.9%. In Group-III hydrothorax
After treatment with neuraminidase the altered subterminal glycans (Galβ- and ascites was in 30%.
(ECL) and αGalNAc- (GSL-I) residues) decreased in LO FGR only. Results: The average value of hydrothorax specific volume was the max-
Conclusion: Changes in the glycome of syncytiotrophoblast appear to imum in Group-I, exceeding the values of Group-II and Group-III by 2.2
the terminal residues of glycans in early-onset FGR. Subterminal glycan and 5.1 times, respectively (p<0.05). The average specific volume of
structures mainly modified in late-onset FGR. It is likely that the modified ascites prevailed in Group-I and exceeded the values of the Group-II
glycome of syncytiotrophoblast may play an important role in pathogen- and Group-III by 1.5 and 4.1 times, respectively (p<0.05).
esis of early-onset and late-onset FGR. Conclusion: The maximum average THI-value is installed in the anterior
chest wall in Group-I (77), exceeding that by 3.4 and 1.7 times in the
Group-III and Group-II (p<0.05). The THI average value in the anterior
PS-16-043 abdominal wall in Group-I (66) higher than in Group-III and Group-II by
MRI lung volume in living and dead newborns: evaluation and 3.01 (p<0.05) and 1.84 times (p>0.05), respectively.
comparison
U. Tumanova1, V. Lyapin1, V. Bychenko1, A. Shchegolev1, G. Sukhikh1
1
NMRCOGP, Russia PS-16-045
Virtopsy possibilities in the diagnosis of the VACTER association in a
Background & Objectives: MRI allows to non-invasive assessment of newborn: a case report
the lungs size and volume in life and postmortem. Data on postmortem U. Tumanova1, V. Lyapin1, V. Bychenko1, A. Kozlova1, A. Shchegolev1
1
lung volumes are necessary for differential diagnosis of intravital and NMRCOGP, Russia
postmortem processes.
Objective: to study and compare the volume indices of the lungs of living Background & Objectives: Postmortem CT and MRI allowed for a non-
and dead newborns without lung pathology using magnetic resonance invasive, objective and clear analysis of the pathology.
imaging (MRI). We report on the Virtopsy of the deceased newborn with VACTER
Methods: Group-I -5 bodies of newborns who died from multiple con- Association.
genital malformations, without lung pathology. Group-II -4 live new- We investigated the body of a male newborn born at gestational age 40weeks.
borns. Postmortem MRI was performed 6–15 hours after death before Fetus ultrasound at gestational age of 20weeks revealed the left kidney agen-
the autopsy. In 3D reconstructions of MR-tomograms, the volume of each esis; on 30weeks - ventricular septal defect, aortic coarctation, anus atresia,
lung, the volume of the thoracic cavity and specific volume of the lungs in open atrioventricular canal. After birth, the newborn underwent surgery:
each observation were calculated. Conducted a comparison and evalua- elimination of the tracheooesophageal fistula and unnatural anus imposition.
tion of the obtained values. Diseases and cause of death verification in the Methods: 3T-MRI and CTwith contrast were performed 10 hours after death
dead newborns carried out at the autopsy. before the autopsy. The analysis of tomograms and 3D-reconstructions were
Results: The smallest volume of the right lung (48.7 ml), left lung (32.8 performed. Virtopsy data were compared with the autopsy results.
ml) and both lungs volume (81.5 ml) were observed in Group-I, and the Results: When the complex Virtopsy identified: Vertebral anomalies (С7
largest - in Group-II (61.6, 44.9 and 106.5 ml, respectively). The average cervical right rib, posterior segments of left ribs I-II and III-V fusion, 12
volume of the right lung in Group-I was 1.3 times less than in Group-II, left rib hypoplasia, deformation of C7 and Th1-5 vertebral bodies);
Virchows Arch

Cardiovascular anomalies (aortic isthmus hypoplasia, superior vena cava PS-17-003

absence, right and left brachiocephalic veins flowing into the right atrium, Assessment of tumour different architecture compounds through
occipital-parietal subcutaneous angiodysplasia); Renal defects (left kid- fractal analysis in prostate adenocarcinoma in correlation with
ney agenesis, right kidney vicarically enlargement). Anal atresia and Gleason and Srigley grading systems
Tracheooesophageal fistula –were operated. Bilateral focal pneumonia, M. Bara1, M.-. Serbanescu2, R.M. Plesea3, V. Ciovica3, A.M. Istrate-
brain edema, anasarca, bilateral hydrothorax, ascites were identified. Ofiteru4, G.C. Rosu4, L. Iovan4, F. Simionescu5, V.T. Moldovan6, I.E.
Conclusion: VACTERL association occurs with a frequency of 1:10000- Plesea7,6,3
1
40000 live births and is a congenital anomalies combination: Vertebral University Emergency Hospital in Bucharest, Romania, 2 Department of
anomalies, Anal аtresia, Cardiovascular anomalies, Tracheo-Oesophageal Medical Informatics and Biostatistics, University of Medicine and
fistula, Renal defects and Limb defects. Pharmacy, Craiova, Romania, 3 Doctoral School, University of
Based on Virtopsy and autopsy data, the VACTER association in the Medicine and Pharmacy, Craiova, Romania, 4 Department of Histology,
deceased newborn was diagnosed at our research case. University of Medicine and Pharmacy, Craiova, Romania, 5 Department
Virtopsy of newborns is recommended for multiple congenital abnormalities. of Pathology, University Emergency Hospital, Bucharest, Romania,
6
Department of Pathology, "Victor Babes" National Institute of
Pathology, Bucharest, Romania, 7 Department of Pathology, "Carol
Tuesday, 10 September 2019, 09:30 - 10:30, Agora 3 Davila" University of Medicine and Pharmacy, Bucharest, Romania
PS-17 | Uropathology
Background & Objectives: The aim of the study is to assess the different
constitutive elements of tumour architecture in correlation with two dif-
PS-17-001 ferent grading systems of prostate adenocarcinoma using the fractal di-
PTEN, ERG, SPINK1 and TFF3 status and relationship in a prostate mension (FD) analysis.
cancer cohort from an Arab population Methods: 433 fields with different patterns of prostatic adenocarcinoma
S. Al Bashir1, M. Alorjani1, N. Aldauod2, O. Halasheh2, M. Al Hamad3, according to Gleason and Srigley grading systems were selected and
I. Matalka2 stained on four serial sections with: H&E for grading and Gömöri tech-
1
King Abdullah University Hospital, Jordan University of Science and nique, Goldner's trichrome, and CD34 immunomarker to assess: tumour
Technology, Jordan, 2 Jordan University of Science and Technology, cells architecture (GO), tumour stroma (TC) and vascular network (VN)
Irbid, Jordan, 3 Dammam University, Saudi Arabia, Jordan respectively. Images were binarized using different approaches, with col-
our focus for Goldner's and CD34 stainings and intensity focus for
Background & Objectives: Prostate cancer (PCa) is the most common Gömöri staining. The FD was computed for each binary image using a
malignancy in men, and is associated with high morbidity and mortality rates. box-counting algorithm. The three computed values were used for clus-
Phosphatase tensin homologue (PTEN) deletions, ETS-related gene (ERG) tering and classification, k-nearest neighbour proving to be a good choice
rearrangements, serine protease inhibitor Kazal type 1 (SPINK1) and trefoil with a classification rate, due to the irregular distribution of cases in
factor 3 (TFF3) overexpression are proposed prognostic biomarkers in pros- different patterns.
tate cancer (PCa). However, their relations and patterns of expression in Results: GO had a more ordered smooth ascending trend towards “area
prostate cancer in a Middle Eastern population are not well studied. like” type of distribution (with FD>1.5in Srigley system than in Gleason
system. TC had almost the same type of distribution – between “linear-
Methods: A cohort of 110 PCa specimens from the archives of King
like” and “area-like” (FD~1.5) in both grading systems. VN had a more
Abdullah University Hospital (Jordan) and Aldammam University
“linear-like” type of distribution (FD<1.5), with a descending trend to-
Hospital (Saudi Arabia), spanning a period from 2005 to 2018. These
wards high-grade patterns in both systems.
cases included 45 radical prostatectomies (RP), 63 transurethral resec-
GO had a direct correlation with TC and VN (“p” value of Pearson’s test
tions of prostate (TURP), and 2 enucleation cases. Tissue microarray
<0.001) while TC and VN proved no correlation (“p” value of Pearson’s
(TMA) of prostate cancer patients was constructed. PTEN, ERG,
test >0.05), irrespective of grading pattern.
SPINK1 and TFF3 expression status was assessed by immunohistochem-
Conclusion: FD analysis proved that Srigley system is more accurate in
istry and correlated with each other.
grading prostate adenocarcinoma than Gleason system.
Results: PTEN loss,ERG and TFF3 expression were observed in 43.6 %,
62.8 % and 44.6 % of PCa cases, respectively. SPINK1 expression was
observed in 6 out of 110 PCA cases (5.4%). In all PCa cases, 3.6% of the PS-17-005
cases showed SPINK1+/ ERG+ phenotype, 1.8% showed SPINK1+/ Small cell carcinoma of the urinary bladder: clinicopathological and
ERG- phenotype, 59% showed SPINK1-/ERG+ phenotype, and 35.4% immunohistochemical features of 11 cases
showed SPINK1-/ERG- phenotype. SPINK1 expression was observed D. Beypinar1, M.F. Acikalin1, D. Arik1, F. Kaya1, A. Ozen2, C. Can2
exclusively in a subgroup of cancers that expressed TFF3 (6/6). There 1
Eskisehir Osmangazi University, Department of Pathology, Turkey,
was an increased PTEN loss and TFF3 expression from Gleason score 6 2
Eskisehir Osmangazi University, Department of Urology, Turkey
(Grade group 1) to Gleason score 9-10 (Grade group 5), the association
was statistically significant with P values of 0.002 and 0.0365, Background & Objectives: Most of the bladder cancers are
respectively. urothelialcarcinoma (UC) which are over 90% percent of diagnosed pa-
Conclusion: In this first study to address the question of PTEN loss, tients. Small cell carcinoma (SmCC) of the urinary bladder is a rare and
ERG, SPINK1 and TFF3 gens status in a predominantly Arab population, highly aggressive tumour. It accounts for less than 1% of all malignant
we documented that PTEN loss and TFF3 expression are associated with bladder tumours and has a poor prognosis.
more aggressive prostate cancers with higher Gleason scores/ Grades. Methods: We searched the electronic database of Eskişehir Osmangazi
SPINK1 expression was observed exclusively in a subgroup of cancers University Hospital from 2010 to 2019 and found 11 cases of SmCC of
that expressed TFF3. These findings support a rationale of screening for the urinary bladder. The demographic data, clinical presentation and
these biomarkers for prognostic purposes and molecular subtyping of the follow-up information were extracted from the medical charts.
disease. Results: The patients consisted of seven men and four women with a
meanage of 70.1years (range, 51-83years). There were 9 cases with trans-
Supported by The Scientific Research Support Fund (SRSF) (MPH/2/17/ urethral resection of the bladder and 2 radical cystectomy specimens.
2015). Ministry of Higher Education and Scientific Research, Jordan. Three patients had pure SmCC while 8 of the tumours were mixed with
 Virchows Arch

other histology. Five of the specimens had also carcinoma in situ. Ten of Paracoccidioidomycosis 2/17 (11.8%), 5. Syphilitic gumma 1/17
the tumours had at least muscularis propria invasion and the other had at (5.9%); and, 6. Tuberculosis 1/17 (5.9%). The patient with syphilitic
least lamina propria invasion. Expression of synaptophysin, gumma in this series was HIV positive. In 6/17 (35%) patients the testic-
chromogranin, CD56, and TTF-1 proteins was found in 10/11 (90.9%), ular lesion was misdiagnosed clinically as malignant tumour resulting in
7/11 (63.6%), 8/8 (100%), and 7/11 (63.6%) cases, respectively. Nine of orchiectomy. In these patients the cause was: malakoplakia (2 patients),
the patients were metastatic either at the time of diagnosis or during idiopathic (2 patients), schistosomiasis (1 patient), and syphilitic gumma
follow-up. (1 patient).
Conclusion: SmCC of the urinary bladder is an aggressive tumour Conclusion: Schistosomiasis and paracoccidioidomycosis are the
characterised by advanced stage at presentation and a propensity for me- most frequent infectious diseases causing granulomatous orchitis
tastasis. SmCC has a poorer clinical outcome than pure UC even if it is a in Brazil. The pathologist must be aware of the pathologic features
small component in mixed tumours. of syphilitic gumma due to increase in frequency of syphilis asso-
ciated with or not with HIV. Unfortunately, in our series, 35% of
patients were clinically misdiagnosed as having malignant tumour
PS-17-006 being submitted to orchiectomy.
What may influence biochemical recurrence in organ-confined (pT2)
prostate cancer, Gleason score ≤6, and negative surgical margins?
A. Billis1, L. Freitas2, L. Costa2, I. Barreto2, A. Botega2, J. Costa2, N. PS-17-008
Almeida2, T. Rotta2 A comparison of grading by summary score and highest grade in
1
State University of Campinas - Unicamp, Brazil, 2 Dep. Anatomic 2,090 biopsy sets with prostate cancer
Pathology, School of Medical Sciences, State University of Campinas M. Bonert1, M. Carvalho2, B. Shayegan1, S. Salama1, A. Kapoor1, I. El-
(Unicamp), Brazil Shinnawy1
1
McMaster University and St. Joseph's Healthcare Hamilton, Canada,
2
Background & Objectives: Detect clinicopathological findings associ- Hamilton Health Sciences, Canada
ated with biochemical recurrence (BR) in patients who usually have very-
low risk for BR following radical prostatectomy (RP). Background & Objectives: Prostate cancer biopsy grading may include
Methods: Step-sectioned and completely processed specimens of 88 a summary score (SS) that is based on assessing the biopsy set as one
consecutive patients considering BR >0,2 ng/mL. Assessed: age, prostate piece of tissue, and may differ from the highest grade (HG) in the biopsy
weight, presence of benign prostatic hyperplasia (BPH), preoperative set. Biopsy-prostatectomy comparisons are confounded by selection bias.
PSA, PSA density, tumour extent evaluated by a semi-quantitative meth- We sought to assess the concordance of the SS and HG in biopsies.
od, clinical stage, and number and percentage of quadrants showing be- Methods: In house prostate biopsy reports at two Institutions from 2011
nign glands at the inked margin (BGIM). to 2017 were extracted and the SS retrieved. A previously validated
Results: 71/88 (80.7%) patients had no BR, and 17/88 (19.3%) had BR; hierarchical free text string matching algorithm (HFTSMA) established
17/17 (100%) patients with BR and 36/71 (50.7%) patients without BR the HG.
had BGIM. Patients with BR had significantly higher number (p<0.001) Results: The study period has 4,477 biopsies and 2,090 had a SS. The
and percentage (p<0.001) of quadrants with BGIM, higher prostate HFTSMA had a 1% error based on pathologists auditing of 700 reports.
weight (p=0.004), higher frequency of BPH (p=0.035), higher level of This was corroborated by a 1% deviation in the ISUP/WHO grade group
preoperative PSA (p=0.044), and less extensive tumours (p=0.050). 1 (WHO1) or Gleason score 6 (GS6); there were 625 WHO1/GS6-SS
Considering percentile 95, cases with >8 and/or >20% positive quadrants cases and 620 WHO1/GS6-HG cases. The 780 WHO2/GS3+4-SS cases
showing BGIM almost always were associated with BR. were by HG 81%WHO2, 15%WHO3, 3%WHO4. WHO3/GS4+3-SS
Conclusion: Benign glands at the inked margin may possibly explain (346 cases) were by HG 66%WHO3, 33%WHO4. WHO4/GS8-SS
postoperative PSA elevation following RP. In step-sectioned and (166 cases) were by HG 1%WHO3, 93%WHO4, 6%WHO 5.
completely processed specimens pathologists should report BGIM in WHO5/GS9&10-SS (173 cases) were by HG 1%WHO4, 99%WHO5.
cases with organ-confined cancer (pT2), Gleason score < 6, and negative The grade by HG and SS was concordant in 86% of cases.
surgical margins. BGIM in >8 and/or >20% positive quadrants, urologists Conclusion: The HG in relation to the SS upgrades 18% WHO2 and 33%
should consider this possibility and avoid immediate treatment unless WHO3 cases. Understanding the significance of this is complicated by
presence of cancer is documented. possible biases associated with grading practices. Adoption of the SS
would result in a downgrade migration and could cause a reverse Will
Rogers Phenomenon. Consensus on prostate cancer grading/reporting
PS-17-007 should be established in conjunction with unbiased outcome data.
Granulomatous orchitis: how often mimics a testicular tumour? A
study in Brazil
A. Billis1, L. Freitas2, L. Costa2, I. Barreto2, D. Losada2, B. Zaidan2, A. PS-17-009
Costa2, A. Herculiani2, K. Araujo2 Slug regulating epithelial-mesenchymal transition is associated with
1
State University of Campinas - Unicamp, Brazil, 2 Department aggressive tumour features, recurrence and reduced survival in pros-
Anatomic Pathology, School of Medical Sciences, State University of tate cancer
Campinas (Unicamp), Brazil A. Børretzen1, K. Gravdal1, S.A. Haukaas2, C. Beisland2, L.A. Akslen3,4,
O.J. Halvorsen1
1
Background & Objectives: There are several causes for granulomatous Centre for Cancer Biomarkers CCBIO, and Gade Laboratory for
orchitis. The pathologic features may be challenging for a proper diagno- Pathology, Department of Clinical Medicine, University of Bergen,
sis and in some cases clinically mimic a testicular tumour resulting in Norway, Department of Pathology, Haukeland University Hospital,
orchiectomy. Bergen, Norway, 2 Department of Clinical Medicine, University of
Methods: We describe the pathologic findings of 17 patients submitted to Bergen, Norway, Department of Urology, Haukeland University
biopsy or orchiectomy and the frequency of cases misdiagnosed clinically Hospital, Bergen, Norway, 3 Centre for Cancer Biomarkers CCBIO,
as malignant testicular tumour. Department of Clinical Medicine, Section for Pathology, University of
Results: Frequency according to cause: 1. Schistosomiasis 6/17 (35.3%); Bergen, Norway, 4 Department of Pathology, Haukeland University
2. Malakoplakia 4/17 (23.5%); 3. Idiopathic 3/17 (17.6%); 4. Hospital, Bergen, Norway
Virchows Arch

Background & Objectives: Epithelial-mesenchymal transition (EMT), im- PS-17-012

portant for tumour cell invasion and metastasis, is a feature of aggressive carci- Oncocytic papillary renal cell carcinoma reveals K-RAS mutation
nomas. We studied the EMT-regulator Slug in different human prostatic tissues C. Choi1, S.S. KIM2, J. KIM3, Y.M. CHO4, H.S. KIM5, K.M. KIM6, K.H.
focusing on EMT, clinico-pathologic phenotype, recurrence and survival. KEE7
1
Methods: Sections from 338 radical prostatectomies (Haukeland Chonnam National University, Republic of Korea, 2 CNUH, Republic
University Hospital, Norway, 1986–2007), 33 castration resistant prostate of Korea, 3 CNUHH, Republic of Korea, 4 Ulsan University, Republic of
cancers, 33 non-skeletal metastases, 13 skeletal metastases, and 41 pros- Korea, 5 Wonkwang University, Republic of Korea, 6 Jeonbuk University,
tatic hyperplasias were immunohistochemically stained for Slug. Republic of Korea, 7 Chosun University, Republic of Korea
Results: Slug was strongly expressed in localized prostatic carcinomas
and skeletal metastases. In localized carcinomas, strong Slug was associ- Background & Objectives: Oncocytic papillary renal cell carcinoma
ated with adverse clinico-pathologic features, such as extraprostatic ex- (OPRCC) is a recently described subtype of papillary renal cell carcinoma
tension, seminal vesicle invasion, high pathologic stage and lymph node (PRCC) characterised by voluminous and intensely eosinophilic cyto-
infiltration. Strong Slug was also associated with strong expression of the plasm, uniform nuclei and low nuclear grade, and indolent biological
EMT transcription factors Twist, Snai1 at tumour-stromal border and behaviour. However, there is still an overlap of histology between
FOXC2, as well as strong HIF-1α and high Ki-67. In univariate survival OPRCC and type 2 PRCC. In this study we aimed to define the clinico-
analyses, strong Slug was associated with shorter time to biochemical pathologic and molecular features of OPRCC by comparing to type 2
recurrence, clinical recurrence, loco-regional recurrence and cancer- PRCC using morphology assessment, immunohistochemical stain, and
specific death. By multivariate Cox’ survival analysis, strong Slug was targeted next-generation sequencing.
an independent predictor of time to biochemical and loco-regional recur- Methods: A cohort of 33 OPRCC and 30 type 2 PRCC was used. Tissue
rence. Among E-cadherin low carcinomas, strong Slug independently microarray (TMA) was made using 3 cores per tumour. They were stained
predicted shorter time to clinical recurrence, skeletal metastases and with CK7, racemase, EMA, E-cadherin, vimentin, CD10. Targeted se-
cancer-specific death (HR 2.3-3.3, p<0.04), together with Gleason grade quencing of 90 cancer-related genes was performed in 28 OPRCC using
groups (≥GG3 vs. ≤GG2). MiSeqDx. PNA-mediated clamping PCR of KRAS was also performed in
Conclusion: The EMT-regulator Slug was associated with aggressive paired normal and tumour DNA of 33 OPRCC and 30 type 2 PRCC cases.
tumour features, recurrence and cancer-specific death in prostate cancer. Results: OPRCC revealed distinct clinocopathologic features: small tu-
Slug and other EMT-regulating transcription factors can be useful as mour size, lower pathologic T stage, and no disease-specific death.
prognostic biomarkers and are potential targets for cancer therapy. Morphologically, they showed peritumoural lymphoid aggregation,
prominent papillary architecture (>80% of tumour), edematous or
hyalinized papillae, inverted nuclear location, and lower nuclear grade.
PS-17-011 Immunohistochemically, they are usually positive for CK7, racemase,
Praja2 expression in non-invasive and muscle invasive urothelial car- EMA and E-cadherin, but not for vimentin and CD10. Recurrent muta-
cinoma of the bladder tions in KRAS were detected in 26 of 33 OPRCC. However, there was no
R. Cepurnaite1, M. Fuggi1, E. Guadagno1, S. Pignatiello1, S. Varricchio1, KRAS mutation in any of the type 2 PRCC.
L. Insabato1 Conclusion: OPRCC reveals distinct clinicopathologic profiles with in-
1
Department of Advanced Biomedical Science of the University of dolent behaviour and unique molecular profiles, which are different from
''Federico II'' in Naples, Italy type 2 PRCC.

Background & Objectives: Urinary bladder cancer is the seventh most

common cancer worldwide. The most common histological type is PS-17-013
urothelial carcinoma. It is usually diagnosed at non-invasive or early The relationship between epithelial mesenchymal transition with
invasive stage, has a high risk of a reoccurrence (50-70%) and progresses Galectin-3 expression in low and high grade urothelial carcinomas
only in 15-25% of cases. of bladder
Praja 2 (PJA2) is an enzyme, that is involved in growth regulation of M. Cin1, A. Igdem Akyildiz2, S. Bektas2, S. Cin3, E. Kimiloglu2, Ö.
various tumours. Our aim was to analyse the expression of PJA2 in Gündogar2, N. Komut2, N. Dursun1
1
muscle invasive and non-muscle invasive urothelial carcinoma of the University of Health Sciences, Istanbul Health Practice and Research
bladder. Hospital, Department of Pathology, Turkey, 2 University of Health
Methods: We analysed 21 different tumours of non-muscle invasive Sciences, GOP Taksim Health Practice and Research Hospital,
(high grade) urothelial carcinoma, which in a period of 6 months or more Department of Pathology, Turkey, 3 Istanbul University Cerrahpaşa
progressed into muscle invasive carcinoma. We built 2 tissue microarrays Faculty of Medicine, Department of Pathology, Turkey
(TMA) from representative areas of each tumour: first TMA contained
non-muscle invasive specimens, second TMA was composed of muscle Background & Objectives: Our aim was to evaluate the relationship
invasive specimens. between clinicopathological parameters and epithelial mesenchymal tran-
Immunohistochemical staining with PJA2/Praja2 antibody was sition (EMT) by immunohistochemical analysis (E-cadherin and
performed. Vimentin) and how EMT interacts with Galectin-3 immunoreactivity in
Results: In first TMA (non-muscle invasive tumours) 15 samples from bladder urothelial carcinomas.
13 patients were evaluable, in second TMA (muscle invasive tumours) 26 Methods: Transurethral resection (TUR) materials of 223 bladder
samples from 21 patients were evaluable. PRAJA2 was expressed in all of urothelial carcinomas were included. Hematoxylin&eosin stained prepa-
them and was scored from 0 (negative) to 3+ (very strong and diffuse rations were reevaluated. Three groups were formed; T1 stage low grade,
positivity). In first TMA 27% of tumours were scored as 3+, 60% as 2+ T1 stage high grade and T2 stage high grade. E-cadherin, Vimentin and
and 13% as 1+. In second TMA 46% of tumours were scored as 3+, 35% Galectin-3 antibodies were applied immunohistochemically to the select-
as 2+ and 19% as 1+. ed paraffin blocks. The staining percentage score and the staining inten-
Conclusion: PRAJA2 was expressed in all samples of high grade sity score were obtained for each marker. The relationship between age,
urothelial carcinoma of the bladder with higher percentage of 3+ score sex, carcinoma in situ, lymphovascular invasion, tumour grade, tumour
(very strong positivity) cases in muscle invasive tumours. Next step in our stage were evaluated with these three markers.
research will be to compare these results with PRAJA2 expression in low Results: There was no significant relationship between age, gender, car-
grade urothelial carcinoma of the bladder and in normal bladder tissues. cinoma in situ and lymphovascular invasion. Additionally, there was no
 Virchows Arch

significant correlation between age, gender, carcinoma in situ and expres- transmembrane glycoprotein Trop2 is highly expressed in many cancers,
sion of E-cadherin, Vimentin and Galectin-3 antibodies. Increased histo- and has different expression profile in certain normal tissues. Trop2 over-
logic grade and stage, presence of lymphovascular invasion showed de- expression is associated with decreased patient survival, tumour aggres-
creased E-cadherin expression and increased Vimentin expression. There siveness and metastasis in many cancers. We aimed to determine the
was no significant relationship between Galectin-3 expression and histo- characteristic features of UUSUCs and to evaluate the relation of clinico-
logical grade. But in high grade carcinomas Galectin-3 expression rate pathological parameters with TROP2 expression.
was higher for T1 stage compared with T2 stage. There is a significant Methods: A total of 45 cases of UUSUC were included from two
correlation between E-cadherin and Vimentin expression. However different centers. Demographic data and histopathological features
Galectin-3 was not significantly associated with both markers. obtained from the hospital records were evaluated retrospectively.
Conclusion: The relationship between prognostic parameters and E- One demonstrative block of each case was stained with TROP2
cadherin / Vimentin expression is significant. There was no correlation antibody. Histopathologic prognostic features such as grade, peri-
between E-cadherin / Vimentin expression and Galectin-3 immunoreac- neural invasion, lymphovascular invasion, tumour necrosis, and
tivity. Galectin-3 and EMT do not show a clear relationship with these surgical margin status were assessed for their relation with
results. TROP2 expression.
Results: Among 45 cases; 39 were male whilst 6 were female. The mean
age was found as 65,64. TROP2 expression was positive in 38(84.4.%)
PS-17-014 cases. Age, grade, stage, localization, differentiation, lymph node metas-
Clinical and morphological characteristics of prostate cancer in tasis, necrosis, lymphovascular invasion, perineural invasion, surgical
Western Romania margin positivity, depth of invasion and metastasis showed no significant
A. Dema1, S. Taban2,3, C. Lazureanu4, D. Herman1, D. Anderco2, M. relation with TROP 2 staining.
Iacob5, M. Botoga4, R. Minciu4, A. Croitor6, V. Dema6 Conclusion: Trop2 was first discovered in trophoblast cells which is
1
Department of Pathology, Emergency Clinical County Hospital "Pius overexpressed by various human carcinomas including, breast, cervix,
Brinzeu", Timisoara, Romania, 2 Emergency Clinical County Hospital colorectal, oesophagus, lung, many lymhomas. Trop2 overexpression
''Pius Brinzeu'' Timisoara, Romania, 3 ''Victor Babes'' University of appears to correlate with poor patient prognosis in these studies, leading
Medicine and Pharmacy Timisoara, Department of Pathology, Romania, to the suggestion that Trop2 could be a therapeutic target for various
4
The Victor Babes University of Medicine and Pharmacy, Timisoara, carcinomas. Although we found no relation of TROP2 expression with
Romania, 5 Department of Pathology, Emergency County Hospital any clinicopathologic factors; our results need to be supported by larger
Timișoara, Romania, 6 Emergency Clinical County Hospital Timisoara, studies with higher number of cases.
Romania

Background & Objectives: Prostate cancer (PC) continues to represent, PS-17-016

mainly in countries that do not benefit from a screening program, a major Trop-2 overexpression may indicate tumour aggressiveness among
health problem because of delayed diagnosis that, consequently, involves prostatic adenocarcinomas
considerable treatment efforts and costs afterwards. This paper analyses Y. Dere1, Į Akarken2, O. Ilhan Celik1, S.Y. Celik1
1
the main clinical and pathological characteristics of patients with PC Mugla Sitki Kocman University, Faculty of Medicine, Department of
diagnosed in Timisoara County Hospital – a reference center for the Pathology, Turkey, 2 Mugla Sitki Kocman University, Faculty of
western part of Romania. Medicine, Department of Urology, Turkey
Methods: The inclusion criteria were: patients with PC diagnosed on
core-needle biopsies (CNB) specimens, during a three-year period Background & Objectives: Prostatic adenocarcinoma is the most com-
(2015 - 2017); the exclusion criteria were: secondary tumours of the mon cancer among men worldwide which has many prognostic and pre-
prostate and treated PCs. The following data were collected: patient dictive factors. The transmembrane glycoprotein, TROP2, which is firstly
age, PSA serum level and histological characteristics of the tumours. described on trophoblastic cells is variably being expressed in many
Results: 486 patients were diagnosed on CNB specimens with PC, hav- cancers. In general TROP2 overexpression was found as associated with
ing a mean age of 70 years. The most affected age group was 60-69 years worse prognosis and tumour aggressiveness. In this study, we aimed to
(40%). The mean serum PSA level was 68 ng/ml. Tumours had an aver- evaluate the relation of clinicopathologic parameters with TROP2
age Gleason score of 7.6. Intraductal carcinoma was associated with expression.
invasive carcinoma in 15.8% of cases, in a group of patients with the Methods: A total of 101 prostatic adenocarcinomas were included.
mean age of 72.8 years, mean serum PSA of 163 ng/ml, mean Gleason Demographic data and histopathological features obtained from
score of 8.14, mean WHO/ ISUP grade of 4. the hospital records and pathology reports retrospectively. One
Conclusion: In the Western part of Romania, patients diagnosed with demonstrative block of each case was stained with TROP2 anti-
prostate cancer are younger, but with more advanced stage of the disease. body. Histopathologic prognostic features such as grade group,
It is necessary to standardize the activities in the services directly involved tumour localization, extraprostatic extension, perineural and
in the diagnosis and treatment of these patients. lymphovascular invasion, surgical margin and lymph node status
and degree of inflammation were assessed for their relation with
TROP2 expression.
PS-17-015 Results: The mean age was found as 64,11. TROP2 was stained over
The expression of TROP2 in the urothelial carcinomas of the upper 10% of the tumoural cells in 64 (63.4.%) cases. Gleason grade group,
urinary system perineural invasion, lymphovascular invasion, ganglionic and seminal
S. Ekmekçi1, Y. Dere2 vesicle involvement, lateral and basal surgical margin positivity showed
1
Izmir Tepecik Training and Research Hospital, Department of significant relation with TROP 2 staining.
Pathology, Turkey, 2 Mugla Sitki Kocman University, Faculty of Conclusion: TROP2 is overexpressed in various human cancers
Medicine, Department of Pathology, Turkey TROP2 overexpression appears to correlate with poor prognosis
leading to the suggestion that TROP2 could be a therapeutic tar-
Background & Objectives: Upper urinary system urothelial carcinomas get for various carcinomas. Our results suggest that TROP2 ex-
(UUSUC), including renal pelvis and ureteral tumours, are rare tumours. pression is higher in advanced tumours and these results need to
Many prognostic and predictive factors are defined in UUSUCs. The be supported by larger studies.
Virchows Arch

PS-17-017 model correctly classifies 80% of patients, in compare to univariate model

GATA-3 expression in urothelial carcinoma and its correlation with (PSA) that correctly classifies 70% of patients.
prognosis Conclusion: MVD is not good diagnostic predictor for prostate
A. Dixit1, K. Sahu1, P. Suresh1, J. Kini1, S. Sreeram1 and G.G.L. Prabhu2 cancer, but due to its relatively high specificity, it represents a
1
Department of Pathology, Kasturba Medical College, Mangalore, India, good complementary data to PSA value. Study represents a dif-
2
Department of Urology, Kasturba Medical College, Mangalore, India ferent approach and contribution to the improvement of prostate
cancer diagnostic methods.
Background & Objectives: According to Indian statistics, Urothelial
Carcinoma is the ninth most common cancer constituting 3.9% of all
malignancies. Markers like GATA-3, CK 5/6, and Cyclin D1 are helpful PS-17-020
in subtyping Urothelial Carcinoma into 'luminal' and 'basal'. GATA-3 is a Abnormal/wild type p53 immunohistochemistry shows high specific-
sensitive and relatively specific marker for 'luminal' subtype of Urothelial ity and positive predictive value for p53 mutation status: time to
Carcinoma. reassess p53 thresholds in bladder cancer
The aim of the study was to gain an understanding of the immunohisto- M. Downes1, A. Hodgson2, S. Kim3, C. Ding3, R. Saleeb3, D. Vesprini4,
chemical expression of GATA-3 in Urothelial Carcinoma and correlate it S. Liu4, B. Xu5, G. Yousef6
1
with the grade and stage to evaluate the prognosis. Sunnybrook Health Sciences Centre, Canada, 2 Sunnybrook Health
Methods: It was a retrospective and prospective cross- sectional obser- Sciences Centre, Canada, 3 St. Michael's Hospital, Canada, 4 Radiation
vational study and included 50 cases. All TURBT specimens of patients oncology, Sunnybrook Health Sciences Centre, Canada, 5 Memorial
morphologically diagnosed as Urothelial Carcinoma and all specimens of Sloan Kettering Cancer Center, USA, 6 Sick Kids Hospital, Canada
radical cystectomy of those patients who haven't received neoadjuvant
chemoradiotherapy were included. Variants of bladder carcinoma, other Background & Objectives: p53 immunohistochemistry is often used as
than Urothelial Carcinoma and recurrent cases were excluded. Further a surrogate for TP53 mutation status. A 10% staining cut off has tradi-
clinical details were analysed. Immunohistochemistry scoring for tionally been used in the evaluation of high grade urothelial carcinoma
GATA-3 was evaluated by the intensity and percentage of nuclear posi- (HGUC) for designation as p53 positive/negative, however recent work
tivity in tumour cells. has shown that an alternate method (0% or >50% - abnormal or 1-49% -
Results: Most Urothelial Carcinomas expressed presence of GATA-3 but wild type) has significant correlation with oncologic outcome. FGFR
some high- grade muscle invasive and basal subtype reflected absence. mutations are frequent in the low grade pathway of UC and should be
Loss of GATA-3 expression was associated with a poorer prognosis. virtually mutually exclusive of HG pathway TP53 mutations. We hypoth-
Conclusion: Molecular subtyping of Urothelial Carcinoma using esized that the alternate method of p53 assessment would show better
GATA-3 immunohistochemical analysis helps in tailoring the ther- correlation with TP53 and/or FGFR mutation status than the traditional
apy based on the molecular signature of the tumour. The reason for 10% cut off.
the researcher's keenness on presenting the study in Europe is the Methods: Tissue microarray sections from a HGUC cohort (cystectomy,
fact that the highest incidence of Urothelial Carcinoma has been ≥pT2) were stained with p53 and scored by two blinded reviewers (n=206).
reported in the continent. Both 10% and abnormal/wild type cut offs were applied. Fifty cases (30
abnormal, 20 wild type) were subsequently examined for p53 and FGFR
status using NEBNext Direct custom ready panel on the Illumina NextSeq
PS-17-019 550 sequencer. The BaseSpace programme was used for alignment and
Angiogenesis assessment in transrectal ultrasound guided prostate variant interpretation. Fisher’s exact test, sensitivity, specificity and
biopsy positive/negative predictive values (PPV/NPV) were calculated.
G. Dordevic1, M. Bembic2, K. Božić3, R. Oguić4, E. Mustać3 Results: 122 cases (59%) showed abnormal p53 staining and 84 (41%)
1
Department of Pathology Medial Faculty, University of Rijeka, Croatia, showed wild type. Using the 10% p53 threshold, 145 were positive (70%)
2
Istrian Health Centers, Hungary, 3 Department of Pathology Medical and 61 were negative (30%). Cases that were p53 abnormal (n=30) had
Faculty, University of Rijeka, Hungary, 4 Urology Clinic, Clinical 15 with p53 mutations, 3 with FGFR mutations and 12 with neither. The
Hospital Centre Rijeka, Hungary wild type group had 1 with p53 mutation, 6 with FGFR mutations and 13
with neither. When the 10% cut off was used, >10% cases (n=32) had 11
Background & Objectives: Prostate cancer screening and diagnosis is p53 mutated cases, 7 FGFR and 14 with neither. <10% group (n=18) had
guided by PSA serum levels and angiogenesis assesment as a new wave 4 with p53 mutations, 3 FGFR and 11 with neither. Using abnormal/wild
of prostate cancer biomarkers could be complementary diagnostic tool. type p53 assessment showed correlation with p53 mutation status
The aim of the study was to evaluate the usefulness of microvessel density (p=0.0007). Using the 10% p53 cut off did not (p=0.523). Neither showed
(MVD) as a diagnostic parameter in early detection of prostate cancer and a significant correlation with FGFR status. Employing abnormal/wild
to compare the blood vessels count in pathohistological samples among type scoring had a specificity of 95% and sensitivity of 50% compared
the most common prostate diseases. with specificity of 78% and sensitivity 34% using the 10% cut off for p53
Methods: This retrospective study included clinical and mutation status. The PPV/NPV for abnormal/wild type was 94% and
pathohistological data and samples from the Urology Clinic and the 56% respectively versus 73% and 40% for the 10% cut off.
Department of Pathology Medical faculty, Rijeka. Prostate cancer biop- Conclusion: Abnormal/wild type p53 staining in HGUC shows signifi-
sies (n = 20), benign prostatic hyperplasia (n = 21) and prostatitis and cant correlation with TP53 mutation status and outperforms the tradition-
nonspecific findings (n = 28) were treated immunohistochemically with ally employed 10% cut-off.
CD31 antibodies. MVD (the number of vessels per high-powered field)
was determined by Weidner method.
Results: Comparison of the MVD in patients with cancer diagnosis with PS-17-021
other diagnoses did not show significant correlation (p=0.097). ROC Tumour immune microenvironment drives prognostic relevance cor-
analysis suggested the cut-off values for MVD (>19.7) and > 6.07 for relating with bladder cancer subtypes
PSA for the prostate cancer diagnosis. Diagnostic model using both pa- M. Eckstein1, P. Strissel2, C. Pfannstiel3, K. Chiappinelli4, D. Sikic5, S.
rameters provided 70% sensitivity and 85% specificity. Logistic regres- Wach5, H. Taubert5, B. Wullich5, B. Keck5, R. Wirtz6, J. Breyer7, M.
sion analysis model that included both parameters showed significance Burger7, W. Otto7, N. Fuhrich3, C. Geppert3, V. Weyerer8, S. Bertz9, R.
(p<0,0001) with high AUC value of 0.809 and p = 0.05. Multivariate Stoehr3, F. Erlmeier3, A. Hartmann3, R. Strick2
 Virchows Arch

1
Institute of Pathology, University Hospital Erlangen, Friedrich- PS-17-022
Alexander-Universität Erlangen-Nürnberg, Germany, 2 Department of Preventative effect of Omega-3 polyunsaturated fatty acids (n-3
Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich- PUFAs) against induction of bladder cancer (BC) in rat model
Alexander Universität Erlangen-Nürnberg, Germany, 3 Institute of Y. Elshennawi1
1
Pathology, University Hospital Erlangen, Friedrich-Alexander Urology and Nephrology Center Mansoura University, Egypt
Universität Erlangen-Nürnberg, Germany, 4 Department of
Microbiology, Immunology, and Tropical Medicine, The George Background & Objectives: The available data in urological literature
Washington University School of Medicine and Health Sciences, regarding the role of n-3 PUFAs in the field of BC chemo-prevention are
Washington D.C., USA, 5 Department of Urology and Paediatric scarce and conflicting. The present work aims to test the chemo-
Urology, University Hospital Erlangen, Friedrich-Alexander Universität preventative effects of n-3 PUFAs against BC induction in a rat model
Erlangen-Nürnberg, Germany, 6 STRATIFYER Molecular Pathology, and the potential anti-neoplastic mechanisms of the drug.
Cologne, Germany, 7 Department of Urology, Caritas Hospital St. Josef, Methods: Ninety male Fisher rats were divided into 3 groups during a 22-
University of Regensburg, Germany, 8 Insitute of Patholoy, University week protocol: group 1 (control), group 2 (Placebo+ N-butyl-N-4-
Hospital Erlangen, Friedrich-Alexander University Erlangen, Germany, hydroxybutyl nitrosamine (BBN) for induction of BC ) and group 3
9
Institute of Pathology, University Hospital Erlangen, Friedrich- received n-3 PUFAs at a daily dose of 1200 mg/kg/day + BBN. At the
Alexander-Universität Erlangen-Nürnberg, Germany end bladder tissues were collected and checked for the presence of ma-
lignancy , markers of angiogenesis (CD34 expression and VEGF relative
Background & Objectives: Muscle-invasive bladder cancer (MIBC) gene expression), inflammation (IL-6), proliferation (KI-67 expressions),
represents approximately two thirds of invasive urothelial bladder cancers redox status (serum MDA) and epigenetic control (miRNA-145 level).
(UBC) and has high morbidity and mortality. Despite intensive efforts to Results: Survival was [30/30 rats (100%) ,18/30 (60%) and 26/
improve patient treatment and outcome, two thirds of patients with UBC 30(86.6%)] for group (1,2 and 3 respectively).There was significant
will have a recurrence or disease progression within 5 years. We conduct- weight loss among rats in group 2(carcinogen) when compared with n-
ed this study to gain further insights in the immunological tumour micro- 3PUFAs rats(group 3) P.value <0.001.The frequency of neoplastic and
environment (TIME). paraneoplastic lesions was less in group 3 when compared with group 2
Methods: sTILs were scored continuously on HE slides in a cohort Staining for CD34 expression and KI-67 were less in group 3 when
of 135 patients with MIBC treated by radical cystectomy (adjuvant compared with group 2.There were significant up regulation of
chemotherapy n= 34) according to current recommendations miRNA-145 expression in group 3 when compared with group 2.
(Salgado et al, 2015). In parallel, we assessed intrinsic subtypes Conclusion: The n-3 PUFAs at our modified dose were able to inhibit
by 21-gene Nanostring signature adapted from the MDACC- tumour growth in the BBN induced rat model of BC, which might be due
subtyping approach. Tertiary lymph structures were assessed by to anti-inflammatory, antioxidant, anti-proliferative, and anti-angiogenic
whole slide immunohistochemistry of CD3, CD8, CD68, and properties together with epigenetic control.
CD79a. Spatial immune profiling was carried out on regionally
(tumour center, invasive margin) designed TMAs by CD3, CD8, We received fund from Urology and Nephrology center, Mansoura
CD56 (NK-Cells), CD68, PD-1 and PD-L1 and revealed spatial University, Egypt.
organized immune phenotypes. Results were validated in 407
MIBC of the TCGA cohort by hierarchical clustering analysis,
immune cell population analysis via CIBERSORT and sTIL- PS-17-023
scoring on digitalized HE-slides. Furthermore, tumour mutational PRMT1 expression is associated with tumour grade, stage, and sur-
burden, neoantigen load and mutational patterns as well as muta- vival of the patients with clear cell renal cell carcinomas
tional signatures were correlated with immune phenotypes in the J. Filipović1, M. Bosić1, S. Ćirović1, M. Životić1, D. Dunđerović2, D.
TCGA cohort. Đorđević3, S. Živković-Perišić4, I. Filipović1, J. Marković-Lipkovski1
1
Results: We demonstrate that quantity and spatial distribution of Institute of Pathology, Faculty of Medicine, University of Belgrade,
stromal tumour infiltrating lymphocytes (sTILs) within the tumour Serbia, 2 Institute of Pathology, Faculty of Medicine, University of
immune microenvironment (TIME) predict stages of tumour inflam- Belgrade, Serbia, 3 Clinic for Urology, Clinical Center of Serbia,
mation, subtypes, patient survival and correlate with expression of Faculty of Medicine, University of Belgrade, Serbia, 4 Institute of
immune checkpoints in an analysis of 542 MIBC. High sTILs indi- Public Health "Dr. Milan Jovanovic Batut", Belgrade, Serbia
cate an inflamed subtype with 80% 5-year disease-specific survival.
A lack of immune infiltrates identifies an uninflamed subtype with a Background & Objectives: Protein arginine methyltransferase-1
survival rate of less than 25%. A separate immune evading pheno- (PRMT1) is associated with the progression of various tumour types.
type with upregulated immune checkpoints associated with poor However, the expression of PRMT1 in renal cell tumours (RCT) is
survival. Within the TIME are tertiary lymph node structures unknown.
(TLS), which can mediate anti-tumour activity via active immune Methods: We evaluated PRMT1 immunohistochemical expression on tis-
cells. High TLS amounts and close tumour distance correlated sig- sue microarray of 194 specimens of RCT, including 120 clear cell renal cell
nificantly with an inflamed phenotype and favourable survival. The carcinomas (ccRCC), 7 papillary RCC type I and 16 type II, 28 chromo-
uninflamed and evasion phenotypes showed lowest TLS numbers phobe RCC (chRCC), 11 renal oncocytomas (RO), 7 collecting duct carci-
and farthest tumour distances and shortest survival. High inflamma- nomas and 5 multilocular cystic renal cell neoplasms of low malignant
tion also correlated with increased neoantigen load, high TMB and potential (MLCRN-LMP). PRMT1 expression in carcinomas was com-
specific mutational patterns (TCGA-MSig1, TCGA-MSig3/4). pared to the tumour grade, stage, age, gender and patient’s survival.
Patients treated with adjuvant chemotherapy showed a favourable Results: PRMT1 immunoreactivity was observed in the majority of
prognosis dependent on high sTILs. ccRCC, RO, all MLCRN-LMP, but in a minority of chRCC (p=0.044).
Conclusion: Determination of sTILs and tumour subtypes may stratify Loss of PRMT1 expression was associated with high-nuclear grade, and
therapy success and patient survival. Considering sTILs can easily be high-tumour stage ccRCC (p=0.014; p=0.044, respectively).Kaplan–
quantified using simple morphological parameters, like hematoxylin-eo- Meier survival analyses revealed that PRMT1 expression in ccRCC, as
sin, sTILs can be implemented for predicting patient survival and out- well as low-nuclear tumour grade and low-tumour stage were significant-
come after adjuvant platinum containing chemotherapy in a routine ly associated with better cancer-specific survival (p=0.029, p<0.001, and
manner. p<0.001, respectively).
Virchows Arch

Conclusion: Loss of PRMT1 may be characteristic of high grade and ≤2, the biopsy-based ISUP-GG more often undergraded [25% (36/143)]
high stage ccRCC. PRMT1 expression could be associated with better than overgraded [12% (8/66)] the RP-based ISUP-GG.
survival of the patients with ccRCC. Conclusion: Biopsy-based ISUP-GG ≤2 is a frequently used criterion for
including patients in active surveillance programs. Unsampled high-grade
This research was supported by Project of Ministry of Education, Science carcinoma is a recognized cause of active surveillance failure. In our
and Technological Development, Belgrade Serbia (number OI175047). cohort, 25% of patients with an initial biopsy-based ISUP-GG of 1-2,
had a final RP-based ISUP-GG ≥3. Recognizing this group of patients
is vital to avoid undertreatment.
PS-17-024
RBM10-TFE3 renal cell carcinoma characterised by paracentric in-
version with consistent closely split signals in break-apart fluores- PS-17-026
cence in situ hybridization: study of ten cases Chromophobe renal cell carcinoma with potential aggressive behav-
M. Furuya1, I. Kato1, M. Baba2, Y. Nagashima3 iour. Histologic and clinicopathologic analysis of 7 cases
1
Yokohama City University, Japan, 2 Kumamoto University, Japan, M.L. Gomez Dorronsoro1, I. Fernadez de los Reyes2, A. Zabalo3, M.
3
Tokyo Women's Medical University, Japan Asiain4, M. Bronte2, M. Mercado2, A. Panizo2
1
CHNavarra. Pamplona. Dpt. Pathology, Spain, 2 CHN. Pamplona. Dpt.
Background & Objectives: Renal cell carcinomas (RCC) associated Pathology, Spain, 3 CHN. Pamplona Dpt. Urology, Spain, 4 CHN.
with Xp11 rearrangement harbors fusion genes involving transcription Pamplona. Dpt. Urology, Spain
factor E3 (TFE3) on chromosome Xp11.2. Dual-colour break-apart fluo-
rescence in situ hybridization (FISH) is recommended to confirm histo- Background & Objectives: Chromophobe renal cell carcinoma
logical diagnoses. Recently, RNA binding motif protein 10 (RBM10), on (ChRCC) is a tumour of low malignant potential, but large scale studies
chromosome Xp11.3, was identified as a chimeric partner of TFE3; thus, have described 7% recurrence/metastases and tumour-related death hap-
RBM10-TFE3 fusion results from paracentric inversion. It is known that pening in 6%-12% (5-10 years) of them.
RBM10-TFE3 RCC may have false-negative results for TFE3 FISH. In a retrospective study, gross and microscopic characteristics of ChRCC,
Methods: We investigated the clinicopathological features of 10 patients recurrences, metastases and survival were evaluated in an attempt to
with RBM10-TFE3 RCC. Histological analysis, immunostaining, dual- identified those pathologic features that might display aggressive
colour break-apart FISH for TFE3, RT-PCR and sequencing were done. behaviour.
Results: RBM10-TFE3 RCCs showed strong nuclear immunoreactivity Methods: ChRCC treated with nephrectomy at our Department from
for TFE3. FISH displayed consistent closely spaced split signals in RCCs 1996 to 2018 with available material for examination were reviewed.
of four patients, and polysomic signals with occasional closely spaced split In aggessive ChRCC, clinical, gross and microscopic features such as
signals in RCCs of six patients. In the latter six patients, five had renal histologic type, microscopic necrosis, vasculo-lymphatic invasion, renal
failure and four developed tumours in hemodialysis kidneys. Five patients vein involvement, perinephric or sinus involvement and TNM were
experienced recurrences including the two who died of metastases. documented
Conclusion: The present study suggests that the carcinogenesis of Results: Thirty ChRCC were detected, seven cases with an adverse out-
RBM10-TFE3 RCC in some, but not all, patients may be associated with come (6 men/1 woman). Except for one case, all showed macro/
chronic kidney disease. microscopic necrosis and that one case presented tumour renal vein
trombosis. Three cases had lymph node and distant metastases at
diagnosis.
PS-17-025 Four patients died from tumour. One patient with sarcomatoid differenti-
Is presurgical biopsy accurate in grading prostatic adenocarcinoma? ation died after 4 months. The other suffered from local recurrences or
A comparison of ISUP Grade Groups and Gleason Scores in a ter- lymph node metastases with a median survival of 64 months (7-179). Old
tiary Institute's cohort of paired needle biopsies and prostatectomies cases did not include the renal sinus among their variables, so two cases
D. Gigliano1, S. Petronilho1, A. Rodrigues1, R. Henrique1 showing T1 stage were probably underestimated.
1
IPO-Porto, Portugal Conclusion: Microscopic necrosis was a common finding in these ag-
gressive ChRCC.
Background & Objectives: Following clinical suspicion of prostatic Sarcomatoid differentiation was associated with a more aggressive
adenocarcinoma, most patients undergo needle biopsy. Apart from behaviour.
confirming the diagnosis, it provides the substrate for evaluating essential The specific study of the renal sinus involvement is indispensable for an
therapeutic and prognostic parameters. Among these, the Gleason Score adequate staging.
(GS) is widely used. Additionally, since the last WHO classification Despite the appearance of metastasic disease, succeeding surgical or on-
(2016), reporting the new set of ISUP Grade Groups (ISUP-GG) is rec- cologic treatment, resolve in longer survival times.
ommended. We aimed to assess the concordance of presurgical needle
biopsy and radical prostatectomies (RP) in regard to GS and ISUP-GG.
Methods: We retrospectively identified a cohort of 209 patients, with PS-17-028
both needle biopsy and corresponding RP diagnosed at IPO-PORTO by A clinicopathological analysis of synchronously multifocal renal cell
one of our two Uropathologists, between Jan/2009 and Dec/2018. neoplasms
Exclusion criteria included known preoperative neoadjuvant treatment G. Gümrükçü1, E. Sayman1, O. Yuksel2, F. Aker1, D. Ertoy Baydar3
1
and incomplete pathologic data. We defined overgrading as a biopsy- Haydarpasa Numune Hospıtal, Pathology, Turkey, 2 Haydarpasa
based GS/ISUP-GG higher than the RP-based GS/ISUP-GG. Numune Hospital, Urology, Turkey, 3 Koc Unıversity, Pathology, Turkey
Undergrading was defined correspondingly. Descriptive statistics were
used to compare GS and ISUP-GG between biopsies and RPs. Background & Objectives: We conducted a retrospective analysis of
Results: Biopsy-based GS and ISUP-GG were identical to their RP- nephrectomies performed in a single clinic to evaluate the incidence of
based counterparts in 70% (147) and 57% (118), respectively. GS synchronous multifocality of RCC and its relation to the stage, grade, size
undergrading/overgrading occurred in 24% (50)/6% (12) of cases, while and histology.
ISUP-GG undergrading/overgrading in 35% (73)/9% (18) of cases, re- Methods: Between 2005 and 2018, we examined 647 kidneys after
spectively. When considering the clinically relevant cut-off of ISUP-GG partial/radical nephrectomy for renal cell carcinoma (RCC).
 Virchows Arch

Results: Of 613 RCCs, 27 (4.4%) contained multifocal malignant or Background & Objectives: Mucinous tubular and spindle cell carcinoma
benign nodules. 6 patients had predisposing genetic syndrome (5 VHL, (MTSCC) is a rare variant of renal cell carcinoma (RCC). This entity shows
1 tuberosclerosis). In 19 cases, multifocality was evident radiologically female preponderance and displays favourable prognosis. We aimed to docu-
whereas it was detected after pathologic evaluation in the rest. The num- ment histopathological characteristics and clinical course of this rare neoplasm.
ber of nodules ranged from 2 to innumerable. The average size of the Methods: We retrospectively reviewed our archive between 2009-2018
lesions was 6.22 (range 0.5-13) cm. Tumours in 19 kidneys were the same and identified 8 cases diagnosed as MTSCC.
histological type:12 clear cell (CCRCC), 2 clear cell papillary Results: There were 4 male and 4 female patients with a mean age of 52.9
(CCPRCC), 1 papillary-type II, 1 sarcomatoid chromophobe (27-72) years. Six patients underwent radical nephrectomy and 2 patients
(ChRCC),1 oncocytic papillary, 1 unclassified RCC and 1 oncocytoma. partial nephrectomy. Two were consultation cases. Gross examination was
Careful histologic examination and immunohistochemistry showed that performed at our Institution in 6 cases. Mean tumour size was 82.5 mm (45-
the ChRCC, PRCC and 8 of CCRCCs had intrarenal lymphovascular 150). In all cases histopathological examination revealed spindle cells with
spread which lead to formation of intraparenchymal satellite multinodules bland nuclei, tubular structures in myxoid stroma and extracellular mucin.
giving the impression of multifocality. Median pT stage and WHO/ISUP Along with classical MTSCC morphology, one case demonstrated sarco-
grade were both 3 in this group of 10 cases. Discordant histologic subypes matous differentiation, scattered papillary structures as well as solid areas.
were found in 8 cases (2CCRCC+Oncocytoma, 1 CCRCC+PRCC, 1 Another case showed large areas of hemorrhage and necrosis accompany-
CCPRCC+ChRCC, 1 ChRCC+Oncocytoma,1 ChRCC+AML,1 ing a clear cell component along with typical areas for MTSCC. Mean
CCRCC+Low grade oncocytic unclassified RCC,1 tuberosclerosis- follow-up time was 48.3±36.8 (range 10-112, median 51.5) months. Only
associated PRCC+AML) two patients with histologically aggressive tumour areas were lost to disease
Conclusion: RCCs with lower stage and grade have a higher tendency of due to metastases within post-surgical 10th and 112th months. No evidence
multifocal nodules with dissimilar histologic subtypes. It seems that in the of recurrence or metastasis was reported in the remaining 6 patients.
case of large infiltrative tumours, the presence of multiple foci may be the Conclusion: MTSCC is a unique renal tumour, generally with an excellent
result of intrarenal metastasis from the main tumour lesion. prognosis subsequent to surgical treatment and should be considered in the
differential diagnosis of spindle cell renal tumours. Adequate sampling and
thorough histopathological evaluation is essential for proper classification.
PS-17-029
Stromal lymphoid response is significantly lower in micropapillary
urothelial carcinomas than in conventional urothelial carcinomas PS-17-032
E. Hacihasanoglu1, K. Behzatoglu2, E.R. Bozkurt3 Detection of AHNAK overexpression in bladder urothelial carcino-
1
Sirnak State Hospital, Turkey, 2 Acibadem Health Group, Turkey, ma cells using quantitative proteomics analysis and immunohisto-
3
Istanbul Training and Research Hospital, Turkey chemical stain
C. Hyun1, S. Song2
1
Background & Objectives: Micropapillary urothelial carcinoma Department of Pathology, Jeju National University Hospital, Republic
(MPUC) is an aggressive urothelial carcinoma (UC) variant. Stromal of Korea, 2 Jeju National University, Republic of Korea
lymphoid response (SLR) status in MPUCs may be responsible for this
and has not been studied before. Background & Objectives: Cytological examination of urine is the most
Methods: Electronical database was scanned for 'invasive UC' in bladder widely used non-invasive pathologic screen for bladder urothelial carcinoma
transurethral resection materials (B-TUR) between January 2010- (BLCA); however, inadequate diagnostic accuracy remains a major challenge.
March 2017. Hematoxylin-Eosin stained slides were re-examined. Methods: We performed high-throughput proteomic analysis of ten paired
Cases with ≥5% MPUC were included and evaluated for age, gender, BLCA and benign urothelial lesion (BUL) samples to identify ancillary
grade, stage, accompanying conventional UC/UC variants, in situ UC/ proteomic markers for use in liquid-based cytology (LBC). Samples were
MPUC, lymphovascular invasion (LVI), necrosis and SLR. SLR was analysed mass spectrometry to identify differentially expressed proteins
scored semiquantitatively as 0-1-2-3. All parameters were also evaluated (DEP) between the two groups. A total of 4,839 proteins were identified
in 50 pure invasive conventional UC cases for comparison. and 111 DEP were confirmed as expressed at significantly different levels
Results: Among 1440 B-TURs, 47 had ≥5% MPUC. Mean age was 69; between the BLCA and BUL groups. Independent proteomic data generat-
87% were male. pT1/pT2 was 23/24. All cases had high-grade features. ed from tissue samples (7,916 identified proteins and 784 DEP), along with
Six were pure MPUC, 13 had other UC variants. Thirty-two had in situ comparative mRNA expression profiles from The Cancer Genome Atlas
UC, 2 in situ MPUC. LVI was present in 8, necrosis in 9. SLR score was 0 were analysed for biomarker discovery.
in 15, 1 in 18, 2 in 9 and 3 in 5 cases. Advanced stage and LVI were Results: Six proteins, AHNAK, EPPK1, HSP90AB1, MYH14, OLFM4,
higher and SLR was lower in MPUCs than conventional UCs. and TUBB, were thereby identified as putative candidate and analysed by
Conclusion: MPUC shows significantly lower levels of SLR than immunostaining. To determine their immunocytochemical expression levels
conventional UC. Our study shows that low levels of SLR correlates in LBC, protein expression was screened using data from The Human Protein
with advanced stage and high frequency of LVI. Status of SLR may Atlas and five proteins were finally selected for immunoreactivity validation
be one of the factors responsible for the aggressive clinical outcome in two independent LBC cohorts. These analyses confirmed AHNAK as a
and also have an important role in impaired therapy response in unique intracellular protein differing in immunohistochemical expression and
MPUCs. subcellular localization between tumour and non-tumour cells.
Conclusion: this study identified a new biomarker, AHNAK, applicable
to discrimination between BLCA and BUL by LBC. To our knowledge,
PS-17-031 the present study provides the first identification of a clinical biomarker
Mucinous tubular and spindle cell carcinoma: a report of 8 cases for LBC based on in-depth proteomics.
from a tertiary center
O. Hurdogan1, H. Karatay2, S. Erdem3, I. Kilicaslan2, Y. Ozluk4
1
Istanbul University, Istanbul Faculty of Medicine, Department of PS-17-033
Pathology, Turkey, 2 Istanbul Faculty of Medicine, Department of Teratoma prepubertal-type of the testis. 20-year experience of La Paz
Pathology, Turkey, 3 Istanbul Faculty of Medicine, Department of University Hospital, with 19 cases
Urology, Turkey, 4 Istanbul University, Istanbul Faculty of Medicine, N. Ibarra1, E. García Fernández1, M. Nistal1, P. González-Peramato1
1
Department of Pathology, Turkey Hospital La Paz, Spain
Virchows Arch

Background & Objectives: Our aim was to review all the teratomas PIN and PCa speaks for its universal character and early event in prostate
prepupertal-type (TPT) (WHO 2016) and assess the age of presentation, cancerogenesis.
histological findings and their behaviour.
Methods: We searched in our database all teratomas in the last 20 years,
selecting for review those without germ cell neoplasia in situ (GCNIS). PS-17-035
Results: We found 72 cases of teratoma. Of them, 19 (26%) were TPT. In Both cytoplasmic and nuclear immunohistochemical staining for
TPT cases, the patients´ age ranged from 10 months to 58 years, being 8 AMP-activated protein kinase is associated with prognosis of clear
(42%) older than 15 years. The histological diagnosis was epidermoid cell renal cell carcinoma and with expression of Smads proteins
cyst in 12 cases (63%), dermoid cyst in 2 cases (11%) and TPT in 5 cases M. Jung1, C. Lee2, J.H. Park3, K.C. Moon4
1
(26%). All cases lacked GCNIS, dysgenetic changes (microlithiasis or Department of Pathol, Seoul National Univ. Hosp., Republic of Korea,
2
Leydig cell hyperplasia), atypia or regressive changes in the adjacent Department of Pathology, Seoul National University Hospital, Seoul,
testicular parenchyma. One case showed Sertoli cell-only. Six cases Republic of Korea, 3 Department of Pathology, SMG-SNU Boramae
(31%) had an organoid pattern. No case showed recurrence or metastasis. Medical Center, Seoul, Republic of Korea, 4 Seoul National University,
The follow-up was between 5 and 19 years. Eight cases (42%) underwent Republic of Korea
radical orchiectomy and 11 (58%) underwent tumour enucleation.
Conclusion: TPT represented 26% of all teratomas. It stands out that 42% Background & Objectives: AMP-activated protein kinase (AMPK), an
were older than 15 years. The histological diagnosis was: epidermoid cyst intracellular energy sensor protein, was known for its tumours-
(63%), dermoid cyst (11%) and TPT (26%). The surrounding testicular suppressive functions against various cancers, including clear cell renal
parenchyma lacked alterations and, except for one case, all adults showed cell carcinoma (ccRCC). In addition, AMPK was reported to downregu-
complete spermatogenesis. Teenagers showed pubertal maturation and late TGF-β/Smad pathway partly by suppressing phosphorylation of
children normal tubule fertility index and normal germ cell maturation. Smad2/3 proteins. We aimed to evaluate the prognostic significance of
No case had recurrence or metastasis. TPT has benign behaviour so testis- immunohistochemical (IHC) staining for pAMPK and its association
sparing surgery could be a valid option in these cases. with the expression of Smads proteins in ccRCC.
Methods: IHC staining for pAMPK (Thr-172), pSmad2 (Ser-467), and
Smad4 was performed on 455 resected ccRCC samples using tissue mi-
PS-17-034 croarray. Cytoplasmic and nuclear IHC staining for pAMPK was mea-
Neuropeptide Y and its receptors (NPY system) in prostate cancer - sured respectively, in semiquantitative manner. Nuclear reaction to Smads
immunohistochemical study proteins was counted with digital analyser. Kaplan-Meier and cox-
W. Wesolowski 1 , E. Iżycka-Świeszewska 2 , A. Gruszecka 2 , J. regression survival analyses were performed. Nuclear expression of
Gulczyński3, D. Sigorski2, E. Szwed4, J. Kitlinska5 Smads proteins were compared between pAMPK-high and -low tumours.
1
EL PAT Co, Poland, 2 Medical University of Gdansk, Poland, 3 Medical In addition, the change of pSmad2 of human ccRCC cell Caki-1 was
University of Gdańsk, Department of Pathology and Neuropathology, investigated with AMPK activator (5-aminoimidazole-4-carboxamide-
Poland, 4 Copernicus Hospital Gdansk, Poland, 5 Georgetown 1β riboside) treatment.
University, USA Results: High cytoplasmic and nuclear expression of pAMPK was ob-
served in 263 (59.1%) and 241 (54.2%) tumours, respectively. High
Background & Objectives: Prostate cancer (PCa) is one of most com- pAMPK expression was predictive of longer progression-free (both,
mon malignancies in men, with high morphological and clinical hetero- p<0.001) and cancer-specific survival (cytoplasmic, p=0.003; nuclear,
geneity, from clinically insignificant to advanced, incurable cases. p<0.001). Furthermore, high cytoplasmic expression of pAMPK was an
Despite many prognostic factors and nomograms, there is no effective independent favourable prognostic factor of progression-free survival
tool to predict disease outcome and cure disseminated cancer. Therefore it (p=0.013, hazard ratio=0.563) when adjusted to grade and stage.
is necessary to search for novel biomarkers and possible future therapeu- pAMPK-high tumours showed higher pSmad2 and Smad4 nuclear ex-
tic targets. One of new directions in oncology are neuropeptides and pression than pAMPK-low tumours (p<0.001). Consistently, pSmad2
relations cancer cells - neural microenvironment. was elevated with pAMPK activation in vitro.
Methods: The material comprised of 51 primary prostate cancer cases and Conclusion: We identified that IHC staining for pAMPK, in either cyto-
11 bone metastases. The patho-clinical data: age, pT feature, Gleason score plasmic or nuclear manner, was significantly associated with prognoses
and Grade Group were considered. Microarray technique was performed on of ccRCC. High cytoplasmic expression of pAMPK was independently
0.5cm tissue cores, with supplement of full slides in some of the cases. associated with favourable outcome of ccRCC. Positive association be-
Among NPY system (NPY, Y1R, Y2R, Y5R) strength of reaction, expres- tween expression of pAMPK and Smads proteins was observed both
sion index (EI) as well as distribution of reaction in cell and tissue were in vivo and in vitro, which may be a novel finding of ccRCC.
evaluated. Perineural invasion and extraprostatic extension areas were
assessed separately. In the same time NPY system were explored in PIN
and benign prostate (BP). ERG status and proliferative index Ki67 was also PS-17-036
assessed. Statistical analysis was performed. Bladder urothelial carcinoma patients under the age of 40 years;
Results: Performed study reveal expression of NPY in PCa and BP with clinical and pathological characteristics and outcomes
quality differences: homogeneous membrane-cytoplasm pattern in cancer Ö. Kaya1, S. Ekmekçi1, E. Kısa2, Ü. Küçük1
1
cells and membranous with apical accentation in BP. Izmir Tepecik Training and Research Hospital, Department of
EI and expression intensity h of NPY receptors were higher in PCa then in Pathology, Turkey, 2 Izmir Tepecik Training and Research Hospital,
BP with correlation among Y2R and Y5R. Moreover PIN, bone metas- Department of Urology, Turkey
tases and PCa displayed similar EI of all NPY system elements.
Interestingly, zonal distribution of immunohistochemical reaction in ref- Background & Objectives: Urothelial carcinoma (UC) is the most com-
erence to all system were seen with markedly higher strength of signal in mon tumour of the urothelial tract. Urothelial carcinoma of the bladder
perineural invasion and EPE areas. There were no statistically significant (UCB) is rare in younger adults and occurs more commonly in older
differences between NPY system and clinico-pathological features. individuals. Objective of this study is to analyse clinical and pathological
Conclusion: The observations indicate activation of NPY system in PCa characteristics of UCB in patients under the age of 40.
and its possible auto and paracrine role, participation in perineural inva- Methods: Nineteen patients who were diagnosed less than 40 years old as
sion and extraprostatic extension. Similar reactivity of NPY elements in UBC in our hospital between 2007-2019, and who had clinical follow-up
 Virchows Arch

were included in this study. Age, gender, symptoms, tumour stage, recur- Results: The expression of 34betaE12 [Me = 13% (3 - 36)] was noted in
rences, disease progression, the postoperative follow up period and survival every control sample and absent in the other groups. AMACR expression
time of the patients were obtained from the patients files. Hematoxylin and was significantly less in ASAP [Me = 10 % (5-15)] than in adenocarci-
eosin stained sections of the tumours were re-evaluated. Tumour growth nomas and was not registered in the controls. The lower was the degree of
pattern, tumour grade, pT stage, tumour differentiation were documented. carcinoma gradation the higher were the index and intensity of АМАСR
Results: The study consisted of 16 (84.2%) male and 3 (15.8%) female expression by atypical epithelial cells of the prostate tumour (from [Me =
patients. The mean age at diagnosis was 32,95 years. One cases (5.3%) died, 42% (28-47)] to [Me = 64% (55-69)]). D2-40 expression was noted in the
18 cases (94.7%) were alive. Nine (47.4%) cases showed papillary growth controls only (Me = 37.5% [14-47]).
pattern, 6 (31.6%) cases papillary and inverted growth pattern. The patho- Conclusion: The 34betaE12, D2-40, and AMACR antibodies make it
logic tumour stages were 8 (42.1%), 7 (36.8%), 2 (10,5%) and 2 (10,5%) for possible to determine the predominant phenotype of ASAP as the follow-
Ta low grade, Ta high grade, T1 high grade and T2 high grade respectively. ing: D2-40 (−), 34betaE12 (−), and P504S (AMACR) (+). This phenotype
Conclusion: Bladder UC is a very rare condition in young patients. Studies determines prostate adenocarcinoma with high probability. The absence of
have suggested that younger patients with urothelial tumours are related to 34betaE12 and D2-40 expression in ASAP, along with the identification of
more favourable outcomes. Our results supported that the younger patients its AMACR-positive phenotype, may be used to identify neoplastic trans-
usually present with low-grade bladder cancer. So clarifying this relation- formation of the epithelium and to consider the early prostate rebiopsy.
ship, further studies including larger patient cohorts are needed.

PS-17-039
PS-17-037 Tertiary Gleason, grade groups and biomarkers for prostate cancer
Expression of 34betaE12, D2-40, and P504S immunohistochemical risk stratification: models and algorithms
markers in atypical small proliferation and prostate adenocarcinomas G. Kharaishvili1, Z. Kolar2, J. Bouchal3, M. Kral4
E. Kazachkov1, A. Dub1, I. Cheter1, D. Voropaev1 1
Department of Clinical and Molecular Pathology, Faculty Hospital in
1
South Ural State Medical University, Russia Olomouc, Czech Republic, 2 Faculty of Medicine and Dentistry, Palacky
University Olomouc, Czech Republic, 3 Department of Clinical and
Background & Objectives: Atypical small acinar proliferation (ASAP) Molecular Pathology, Faculty of Medicine and Dentistry, Olomouc,
is a problematic diagnostic category, the essence of which should be Czech Republic, 4 Department of Urology, Faculty Hospital in
clarified by determining its immunohistochemical phenotype. Olomouc, Czech Republic
Methods: We used prostate biopsy samples obtained from 90 patients,
which were divided into 6 groups according to the morphological diag- Background & Objectives: Tertiary Gleason patterns are reported with
nosis: ASAP and the carcinomas of Grade Groups 1-5. Normal prostate increasing frequency in relation with disease recurrence (Epstein et al 2012,
tissue samples served as controls. We performed an immunohistochemi- Trock et al 2009). A new contemporary prostate cancer grading system was
cal staining method using 34betaE12, D2-40, and P504S antibodies. We proposed in 2014 for accurate grade stratification (Egevald et al 2016). We
applied non-parametric statistical methods. have previously reported association between periostin, Skp2 and Slug in
Results: In the control group, the marker 34betaE12 expression [Me = aggressive prostate cancer. We decided to verify association of tertiary
13% (3 - 36)] was noted in 100% of cases. In ASAP and Grade Group 1-5 Gleason and ISUP contemporary grade groups with expression of these
adenocarcinomas, there was a complete absence of 34betaE12 in all and other selected proteins in our patients using mashine learning tools.
cases. P504S expression was significantly less in the group of patients Methods: Formalin fixed paraffin embedded tissues of 101 prostate carci-
with ASAP [Me = 10 % (5-15)] than in adenocarcinomas of Grade nomas were stained immunohistochemically for PSA, periostin, versican,
Groups 1-5 and was not registered in the controls. The lower was the E-cadherin, beta-catenin, vimentin, Skp2, Slug, Ki67, p53, androgen recep-
degree of carcinoma gradation the higher were the index and intensity of tor, and scored. Slides were reviewed for the presence of tertiary Gleason
P504S expression by atypical epithelial cells of the prostate tumour. The (worse than the primary and secondary grade, usually pattern 4 and 5).
level of D2-40 expression in the basal epithelial cells was discovered only Carcinomas were classified into localized, advanced and metastatic groups,
in the control samples (Me = 37.5% [14-47]). In ASAP and Grade Group and ISUP 2014 Gleason grade groups (GG1-5 [1=GS≤6; 2=GS3+4;
1-5 adenocarcinomas, D2-40 was not expressed. 3=GS4+3; 4=GS8, 5=GS9-10], Pierorazio et al 2013 and Epstein et al
Conclusion: Therefore, 34betaE12, D2-40, and P504S markers make it 2016). Statistical analysis was performed by SPSS and STATISTICA soft-
possible to determine the predominant phenotype of ASAP as the follow- wares. Hierarchical cluster analysis (average linkage, within groups) was
ing: D2-40 (−), 34betaE12 (−), and P504S (+). This phenotype indicates done to identify subgroups based on protein expression. Kohonen impor-
the presence of prostate adenocarcinoma with high probability. tance network was generated for accurate clustering and associations.
Results: Tertiary Gleason was recognized in 22% of radical prostatecto-
my cases, it was more frequent in advanced and metastatic tumours
PS-17-038 (p<0.001). It also positively correlated with total preoperative PSA (Rs
Immunohistochemical evaluation of the lymphatic vessels in atypical 0.303, p=0.003), Ki67 (Rs 0.209, p=0.045) and periostin stromal expres-
small acinar proliferation and adenocarcinomas of the prostate sion (Rs 0.276, p=0.008) while negative correlation was observed for
E. Kazachkov1, A. Dub1, I. Cheter1 membrane-localized beta-catenin (Rs -0.211, p=0.035). Gleason grade
1
South Ural State Medical University, Russia groups were in negative association with E-cadherin (Rs -0.203,
p=0.045) while with nuclear Skp2 and periostin stromal expressions
Background & Objectives: Currently, there is a lack of a reliable algo- showed positive association (Rs 0.338 and 0.269, p=0.001 and 0.008,
rithm for differential diagnosis of nonneoplastic, premalignant processes, respectively). Periostin stromal positivity correlated with versican stromal
and prostate adenocarcinomas. Moreover, atypical small acinar prolifer- expression (Rs 0.368, p<0.001) and stromal versican correlated with stro-
ation (ASAP) is a problematic diagnostic category, therefore its immuno- mal vimentin (Rs 0.332, p=0.001). Chi-square test based correlation net-
histochemical phenotype should be clarified. work showed significant relationships between AR, GS groups, stage and
Methods: We divided prostate biopsy samples of 90 patients into 6 clusters (p<0.001, =0.006, =0.004, respectively). Kruskal-Wallis Anova
groups according to morphology (ASAP and the carcinomas of Grade test revealed significant differential expressions of stromal periostin
Groups 1-5). Normal prostate tissue samples served as controls. We per- (p=0,017), stromal versican (p<0.001), as well as Skp2 (p<0.03) and
formed immunohistochemistry using 34betaE12, D2-40, and P504S AR (p<0.001), in different clusters. Models for conditional high risk
(AMACR) antibodies and applied non-parametric statistical methods. groups identified Ki67 as an important predictor.
Virchows Arch

Conclusion: For the first time, we showed significant association of Results: It was established that the frequency and intensity of expression
grade groups GG4/5 and tertiary Gleason with periostin, Ki67, Skp2 of SC markers correlated with the tumour stage and the degree of cellular
and beta-catenin. Cluster analysis revealed significant differences of anaplasia. The SC markers used in the study expressed in all types of UC
versican, periostin, AR, tertiary Gleason and Grade Groups between pa- and did not differ in both frequency and expression intensity.
tients clusters. Larger cohorts are further needed to accurately identify Conclusion: Tumour cells of different UC can maintain SC markers,
potentially aggressive prostate cancer using selected models. reflecting the degree of their immaturity. The number of stemless tumour
cells correlates with the stage of the tumour progression and the progno-
Supported by MH CZ – DRO (FNOl, 00098892). sis. The revealed features of the expression of SC markers will make it
possible to develop new approaches to the treatment of urothelial carci-
nomas.
PS-17-040
Renal cell carcinoma in patients 40 years of age or under: a single-
center experience PS-17-042
M. Kilic1, S. Ekmekci2, E. Kisa3, U. Kucuk4 Pathology of testes in male addicts
1
Tepecik Education & Research Hospital, Department of Pathology, N. Krupnov1, A. Astrakhantsev2
Turkey, 2 Izmir Tepecik Training and Research Hospital, Department of 1
Bureau of Forensic Medicine, Ryazan, Russia, 2 Central Clinical
Pathology, Turkey, 3 Tepecik Education & Research Hospital, Hospital №2 named after N.A. Semashko, Moscow, Russia
Department of Urology, Turkey, 4 Izmir Tepecik Education and
Research Hospital department of Pathology, Turkey Background & Objectives: Drug use causes the development of not
only mental dependence, but also damage to internal organs.
Background & Objectives: Early-onset Renal Cell Carcinoma (RCC) Objective: Morphological analysis of testicular structural changes in men
patients differ in survival, stage and tumour type compared to older pa- with drug addiction.
tients. In this study, stages, histopathological features and their relation- Methods: The testicles of 42 patients aged 20–35 years who suffered
ship with survival at early-onset RCC are evaluated. from inject opioid (desomorphine) addiction and dead from accidents
Methods: Twenty-one patients who were diagnosed as RCC in our hospital were studied. The control group consisted of 18 healthy testicles from
between 2008-2018 and who were aged 40 or under were included in this men of the same age who died from accidents. Macroscopic, histological
study. Age, gender, tumour size, tumour stage, histological subtype, Fuhrman and morphometric studies of testicular tissue were performed.
grade, renal capsule invasion (RCI), perinephric fat invasion (PNFI), renal Results: In macroscopic examination, the testicular mass in drug addicts
sinus fat invasion (RSFI), necrosis, survival status were documented. (32.35 ± 1.22 g) on 26.9% less than the value of control group. When
Results: The study consisted of 10 male,11 female patients. One of the morphometric analysis of histological preparations of drug addicts
male patients had Von Hippel Lindau Syndrome. The mean follow-up testicles, the volume of the tunica albuginea (2.67 ± 0.37 cm3) is less than
period was 43.8 months. Three of the patients died because of the disease. the values of the control value by 13%. The volume of the testicular
Nine (42.8%) cases were clear cell RCC (CCRCC), 5 (23.8%) network (0.39 ± 0.09 cm3) is less than the control by 31.6%, and the
Chromophobe RCC, 2 (9.5%) Translocation RCC, 3 (14.2%) RCC, Not volume of the convoluted seminiferous tubules (7.50 ± 1.59 cm3) - less
Otherwise Specified, 1 (4.7%) RCC Papillary type 1, 1 (4.7%) RCC by 55%. Along with the lesion of the canalicular apparatus, at drug ad-
Papillary type 2. Eighteen cases were stage 1, 3 were stage 3. Necrosis diction revealed focal necrosis of the seminiferous tubules and an increase
was present in 3, PNFI in 2, RSFI in 2, RCI in 6 cases. Statistical analysis of interstitial connective tissue volume (6.10 ± 1.13 cm3) by 20.0% com-
revealed that PNFI, RSFI, RCI, necrosis, stage were significantly associated pared to the control group.
with survival (respectively, p=0.003, p=0.009, p=0.017, p=0.047, p<0.01). Conclusion: In male-drug addicts, a decrease in testicular mass and vio-
Conclusion: In young adults under 40 years RCC is seen in a very low lation of their structure, mainly in the form of a decrease in the absolute
ratio. In the English literature that approximately 80% of RCCs in young volume of the seminiferous tubules and interstitial connective tissue has
adults are CCRCC, and most of them are low stage. Most of the cases in been found.
our series were low stage CCRCC with good prognosis as in the litera-
ture.
PS-17-043
Performance of an AI-based cancer diagnosis system in France's
PS-17-041 largest network of pathology Institutes
Stem cell markers in urothelial carcinomas and their prognostic D. Laifenfeld1, J. Sandbank1, C. Linhart1, L. Bien1, D. Raoux2
1
value Ibex Medical Analytics, Israel, 2 Medipath, France
E. Kogan1, Y. Osmanov1, S. Demura1
1
First Moscow State Medical University (Sechenov University), Russia Background & Objectives: Prostate cancer is the second leading cause
of cancer-related deaths, compounded by complexity of diagnosis, insuf-
Background & Objectives: The question of the presence of cancer stem ficient diagnostic reproducibility, and a growing shortage in pathologists.
cells (SC) in urothelial carcinomas (UC) of various immunophenotypes is Ibex Medical Analytics, focusing on AI-based cancer diagnostics, has
currently open. The possibilities of a number of potential markers of stem developed an algorithm that identifies various cell types, tissue structures
in tumour cells for the determination of cancer SCs in urothelial carcino- and morphological features within whole slide images of prostate core
mas and their prognostic significance are discussed. The purpose of the needle biopsies (PCNBs), such as cancerous glands (of Gleason patterns
study is a comparative assessment of the expression of stem markers in 3, 4 and 5), high-grade PIN, and inflammation. The algorithm utilizes
different immunophenotypes of UC and the determination of their prog- state-of-the-art Artificial Intelligence (AI) and Machine Learning tech-
nostic significance. niques and was trained on hundreds of thousands of image samples, the
Methods: Material and methods. The study was performed on surgical majority taken from hundreds of manually annotated PCNBs from
material from 196 patients with UC of the renal pelvis and bladder. Maccabi Healthcare Services centralized pathology lab. Medipath is the
Immunohistochemistry was performed on paraffin sections using a stan- largest network of pathology Institutes in France, servicing 370000 pa-
dard protocol. The antibodies used were: ALDH1A1, CD133, CXCR4, tients including 5000 prostate biopsies annually. The goal of this study
NANOG, OCT4, SOX2 ("Abcam"), CD24, CD105 ("Invitrogen"), was to assess the performance of the algorithm on benign slides from 4
CD31, CD34 ("Novocastra"). different labs within the network, and to assess the error rate in these labs.
 Virchows Arch

Methods: 150 anonymized cases with pre-specified features were used Methods: Seventy Paraffin embedded prostate cancer tissue specimens
for calibration of the prostate algorithm to the Medipath preanalytic pro- were retrospectively collected from 2009 to 2013 at Korea University
cesses. Upon calibration, 100 consecutive anonymized benign cases were Anam Hospital. All of the specimens were samples of radical prostatec-
scanned with a Philips UFS Scanner, uploaded to the Ibex cloud and tomy with pathologically proven acinar adenocarcinoma. The expression
analysed by the prostate algorithm. of YAP1(anti-YAP1, diluted 1:1000) was determined by immunohisto-
Results: The performance of the algorithm on the benign cases will be chemistry, scored by sum(0-8) of proportional score(0-5), and intensity
discussed, including details on the confidence levels and identification of score(0-3), and the expression of UCA1 were determined by RNA in situ
various features within the cases/slides. hybridization according to the manufacturer’s instructions, scored from 0
Conclusion: AI-based algorithms such as developed by Ibex can be used to +3.
in various stages of the diagnostic process, to enable higher accuracy in a Results: The expression of UCA1 was significantly correlated with the
fraction of pathologist effort and time, enabling faster turn-around-time presence of extraprostatic extension, seminal vesicle invasion, pathologic
and the diversion of resources to increase lab throughput. T stage, and high or very high risk group according to the NCCN guide-
line. (p<0.05) On the other hand, it did not show significant correlation
with lymphatic invasion, prognostic group, Gleason’s score, recurrence,
PS-17-044 resection margin involvement, and disease free survival. Importantly, we
PDL1 protein expression and mRNA expression in TFE3 transloca- found that UCA1 overexpression is correlated to increased nuclear YAP1
tion renal cell carcinoma are associated with poor prognosis expression.
H.J. Lee1 Conclusion: The present study revealed increased UCA1 in prostate
1
Pusan National University Yangsan Hospital, Republic of Korea cancer with poor clinicopathologic factors, supporting evidence of poten-
tial diagnostic and therapeutic efficacy. Also, we can propose new insight
Background & Objectives: Renal cell carcinoma (RCC) is widely rec- into the role of UCA1 through Hippo pathway in prostate cancer patho-
ognized as a heterogeneous disease with various histological subtypes. genesis.
Xp11.2 translocation RCC (tRCC) is a rare subtype, recognized as a
distinctive pathological entity in the 2004 WHO renal tumour classifica-
tion and it shows poor prognosis. Due to its chemoresistant phenotype, PS-17-046
the mainstay of therapy for advanced RCC had been systemic immuno- The prognostic value of PD-L1 and CTLA-4 immunoexpression in
therapy. In this study, we tried to evaluate the result of PDL1 expression in immune cells and in tumour cells of testicular germ cell tumours
tRCC, and examined lymphocyte infiltration with relation of prognosis. J. Lobo1, A. Rodrigues1, R. Guimarães1, M. Cantante1, P. Lopes1, C.
Methods: Immunohistochemistry (IHC) for PD-L1, FOXP3 and CD8 Jerónimo1, R. Henrique1
1
expression in FFPE tissue sections were cut in 5-mm slices. IHC analysis IPO Porto, Portugal
was performed on tumour samples using antibodies against PD-L1 (E1L3
and SP142) and T cell proliferation for FOXP3 and CD8. TIL density Background & Objectives: Novel less toxic treatments for testicular
score based on a 0–3 scale as follows: 0, no TILs; 1 (mild), <5% of the germ cell tumour (TGCT) patients are needed. Immunotherapy is on
tumour area with TILs; 2 (moderate), 5–50% of the tumour area with the brink, but has been scarcely explored in TGCTs, which naturally
TILs; and 3 (diffuse/marked), >50% of the tumour area with TILs. contain prominent immune infiltrate, especially seminomas. We
Results: We did western blot for PDL1 expression in ASPL-TFE3 trans- aimed to assess the immunoexpression of immune-checkpoints
location RCC cell line and clear cell RCC cell line. ASPL-TFE3 translo- PD-L1/CTLA-4 in a cohort of TGCTs and seek for clinicopatholog-
cation RCC cell line expressed PDL1 strongly in western blot. Patients ical correlates.
with PD-L1+ tumour cells were significantly more likely to progress Methods: A total of 162 consecutively diagnosed patients (2005-2017)
disease from tRCC compared with patients without PD-L1+ tumour cells were included. In mixed tumours immunostaining was evaluated individ-
(P < 0.02). In Kaplan- Meier survival analysis, TILs high groups were ually for each tumour component (total of 271 tumour samples). CTLA-4
correlated with progression free survival (p<0.001). and PD-L1 (clone 22C3) immunoexpression were assessed both in im-
Conclusion: We found that PDL1 expression and TILs with CD8+ pro- mune cells (ICs) and tumour cells (TCs), considering both intensity/
liferation in tRCC were correlated with poor prognosis. Overall, the cur- proportion of positive cells. In the 109 seminoma samples the immune
rent findings indicated that the expressions of PD-L1 protein and mRNA infiltrate was further characterised by CD20/CD3/CD4/CD8/CD56/
PD-L1 may serve as a potential marker of invasiveness and prognosis. CD68.
Also, the high expression of PD-L1 in tRCC would be possible to clini- Results: 156/162 (96.3%) and 136/160 (85.0%) TGCTs exhibited
cally adopt the immunotherapy for targeting PD-L1. CTLA-4- and PD-L1-positive ICs, with no significant differences among
seminomas/non-seminomas. Patients with <20% CTLA-4-positive ICs
showed significantly more rete testis/lymphovascular invasion
PS-17-045 (p=0.0474,p=0.0312) and pT2-3 stage (p=0.0325); those with absent
The clinicopathologic significance of long non-coding RNA urothelial PD-L1-positive ICs showed significantly more relapse and
cancer associated 1 via Hippo pathway in prostate cancer Intermediate/Poor IGCCCG (p=0.0078,p=0.0300). 235/262 (89.7%)
H. Oh1, Y.J. Lee2 and 65/262 (24.8%) samples showed TCs positive for CTLA-4 and PD-
1
Korea University Anam Hospital, Republic of Korea, 2 Korea L1, respectively. Teratomas, choriocarcinomas and yolk sac tumours ex-
University Anam Hospital, Republic of Korea hibited significantly higher intensity staining in TCs for CTLA-4
(p<0.01). Choriocarcinomas and teratomas displayed significantly more
Background & Objectives: Although overexpression of long non- and less frequent PD-L1-positive TCs, respectively (p<0.05).
coding RNA Urothelial Cancer Associated 1(UCA1) has been involved Conclusion: These preliminary results demonstrate the prognostic value
in several human cancers, its biological functions in prostate cancer have of immunoexpression assessment of immune-checkpoints in TGCTs and
not been identified. Yes-associated protein 1(YAP1), a transcription co- point towards a possible clinical benefit of agents targeting PD-L1/
factor, is a key component of Hippo pathway. When YAP1 is translocated CTLA-4.
into the nucleus, it promotes cell proliferation, inhibits apoptosis, and
plays an oncogenic role. The aim of this study is to assess the clinico- Supported by PhD Grant by FCT (grant number SFRH/BD/132751/
pathologic significance of UCA1 and determine their association with 2017). Project Grant by FCT (grant number POCI-01-0145-FEDER-
YAP1 in prostate cancer. 29043).
Virchows Arch

PS-17-047 molecular-based testing of urine samples for tumour diagnosis and sur-
Programmed Death Ligand-1 (PD-L1) immunohistochemical assess- veillance will need to take account of this finding.
ment using QR1 clone in muscle-invasive urothelial carcinoma: a
comparative study with 22C3 clone
A. Loghin1, A. Nechifor-Boila1, A. Borda1, I.A. Nechifor-Boila2, S. PS-17-049
Voidazan3, E. Dee1, M. Decaussin-Petrucci4 Is intraoperative frozen section consultation during nephron sparing
1
Department of Histology, UMFST Targu-Mures, Romania, surgery really warranted? An audit from a tertiary oncology center
2
Department of Anatomy, UMFST Targu-Mures, Romania, S. Menon1, G. Bakshi2, G. Prakash3, A. Joshi4, S.B. Desai5
3 1
Department of Epidemiology, UMFST Targu-Mures, Romania, Department of Pathology, Tata Memorial Hospital, Mumbai, India, 2
4
Department of Pathology, Centre Hospitalier Lyon Sud, Hospices Tata Memorial Centre Mumbai India, India, 3 UroOncology, Tata
Civils de Lyon, Universite Lyon 1, Pierre Benite, France Memorial Centre, India, 4 Tata Memorial Centre Mumbai India, India, 5
Pathology, Tata Memorial Centre, India
Background & Objectives: PD-L1 immunohistochemistry (IHC) is used
to guide treatment decision regarding the use of checkpoint immunotherapy Background & Objectives: Small renal masses are now amenable to be
in urothelial carcinoma (UC). QR1 (Quartett) is a novel PD-L1 IHC assay treated by nephron sparing surgery. Our aim was to retrospectively ana-
with proven efficiency in lung cancer, but no data in UCs. The aim of our lyse the pathologic characteristics of nephron sparing surgery (NSS) seen
study was to compare the performances of QR1 PD-L1 IHC expression to at our Institute with emphasis on intraoperative frozen section margin
22C3 clone (Dako) (one of the approved antibody for UCs), in a cohort of assessment.
muscle-invasive UCs. Methods: A 10-year retrospective clinico-pathologic analysis of NSS
Methods: Our study included 69 UC cases. PD-L1 IHC status was assessed seen at our Institute was done. The histopathology slides were reviewed
using both QR1 and 22C3 clones. Combined Positive Score (CPS), percent- and frozen section data was recorded. Patient demographics and follow-
age of positive tumour cells (TC) and tumour-infiltrating immune cells (IC) up was obtained from electronic medical records.
were determined. The positivity cutoffs were set at CPS ≥10, TC and/or IC Results: 115 cases of NSS patients were identified. 105 cases had a
≥25%. Cohen’s kappa statistics were used to compare scoring methods. malignant diagnosis of which the commonest was conventional renal cell
Results: Among all the 69 cases, 28(40.6%) were considered positive carcinoma (81 cases). 81 cases had pathologic stage 1 (pT1) tumours with
when using CPS assessment for both QR1 and 22C3 clones, with a kappa median tumour size of 3.2 cm. Intra-operatively frozen margin was pos-
agreement factor of 0.880 (p<0.001). When the percentage of positive TC itive in 18 /74 cases (24.3%) of which 10 were revised. The mean margin
and/or IC ≥25% was considered as positive for QR1 and CPS≥10 for for all cases was 2.1mm. Only two patients of Type 2 papillary renal cell
22C3, respectively, the corresponding kappa factor was 0.791 (p<0.001). carcinoma, developed recurrence during the period of follow-up.
Conclusion: Our study is the first one demonstrating that QR1 clone can Conclusion: Intraoperative frozen section consultation has a minimal role
be used to evaluate PD-L1 status in UCs, with a very good agreement rate in evaluation of margins of NSS as even close/positive margins are not
compared to 22C3 clone. The best agreement factor was obtained when associated with an increased risk of local recurrence in small renal tu-
CPS was applied for QR1 evaluation. Consequently, QR1 clone could be mours. Mini margins of even less than 5mm are associated with excellent
an alternative antibody in PD-L1 IHC status assessment to guide treat- loco-regional control of disease.
ment decision regarding the use of checkpoint immunotherapy in UC.

This work was partially supported by the University of Medicine and PS-17-050
Pharmacy of Targu-Mures Research Grant number 15609/5/29.12.2017. Collecting duct carcinoma of kidney: a clinicopathologic and immu-
nohistochemical study of 12 cases from a single tertiary oncology
centre
PS-17-048 S. Menon1, G. Bakshi2, A. Joshi2, S. Desai2
1
Genomic instability in morphologically normal urothelium in pa- Department of Pathology, Tata Memorial Hospital, Mumbai, India, 2
tients with low grade (LG) and high grade (HG) urothelial carcinoma Tata Memorial Centre Mumbai India
(UC)
T. McHale1, K. Gilligan2, R. Dwyer2, S. Bastacky3 Background & Objectives: Collecting duct carcinoma (CDC) com-
1
HSE/NUIG, Ireland, 2 NUIG, Ireland, 3 UPMC, USA prises less than 1% of all renal tumours. Our objective was to study the
clinicopathological and immunohistochemical (IHC) features of
Background & Objectives: In this study we examine the level of geno- collecting duct carcinoma of kidney at our Institute.
mic instability in background normal urothelium at the time of presenta- Methods: Cases of collecting duct carcinoma were searched on the elec-
tion of patients with low grade and high grade urothelial carcinoma. tronic pathology database over a period of six years. The histopathology
Methods: Using loss of heterozygosity analysis (LOH), we compared the slides and immunohistochemistry (IHC) were reviewed. The clinical de-
level of fractional allelic loss (FAL) in microdissected and anatomically tails and follow up of these patients were obtained from electronic med-
separate samples of normal urothelium and matched tumour samples in ical records and case files.
LG and HG UC patients. A panel of 20 microsatellite (MS) markers was Results: Twelve cases of collecting duct carcinoma of kidney were retrieved.
used. FAL was calculated as the number of loci with LOH / the number of Ten were males and two patients were female. Median age was 50 years. Six
informative markers. 22 LG and 12 HG (all pT0) cases were analysed. cases were Stage III and 2 were stage IV. The tumour cells were variably
Results: The mean FAL for LG and HG UC was 0.48 and 0.44, respectively arranged in cords, trabeculae, and tubulo-papillary pattern. Desmoplasia, ne-
(not significant). FAL for normal urothelium in patients with LG and HG crosis and wreath- like periglomerular tumour spread was noted (100% cases).
carcinoma was 0.49 and 0.41, respectively (not significant). For LG UC IHC for CK19, CK7 and HMWCK was positive in 91% cases. Two patients
patients at first presentation, mean FAL of tumour was 0.49 and of normal developed metastasis locoregional and distant metastasis within 2 years.
urothelium was 0.5. Mean concordance between tumour and normal Conclusion: Collecting duct carcinoma of kidney is a rare renal cancer.
urothelium for pattern of LOH across all MS markers was 0.56 for LG and The morphological characteristics are variable and careful gross, micros-
0.62 for HG UC. copy and ancillary immunohistochemical marker evaluation is necessary
Conclusion: The level of genetic instability by LOH in normal for correct diagnosis and patient management. The prognosis is dismal
urothelium in patients with UC is similar to that present in tumour tissue, and research is needed to develop better therapies for this aggressive
even for patients at first presentation of LG UC. The development of subset of renal cancer.
 Virchows Arch

PS-17-051 localization of protein staining (nuclear and/or cytoplasmic) was also

Analysis of tumour depth invasion with Smoothelin antibody in determined.
equivocal TURBT surgical specimens Results: GLI3 and PTCH1 were overexpressed in epithelium (P<0.0001
I. Mihai1, B. Nataras2, D. Herman2, G.E. Olteanu1,3, A. Gheju1, A. for both), but not in stroma. GLI3 localization in epithelium was mostly
Jurescu1, O. Vita4, A. Cumpanas5, R. Bardan5, A. Dema2 diffuse (nuclear and cytoplasmic), while cytoplasmic GLI3 localization in
1
Department of Pathology, University of Medicine and Pharmacy "Victor stroma was negatively associated with Grade Group (P<0.0001). Same was
Babes", Timisoara, Romania, 2 Department of Pathology, Emergency observed for PTCH1 localization in epithelium and stroma (P<0.0001 for
Clinical County Hospital "Pius Brinzeu", Timisoara, Romania, 3 Centre both). In prostate inflammation samples prevails cytoplasmic PTCH1,
for Gene and Cellular Therapies in Cancer - Oncogen, Romania, while in benign prostate diffuse. All HH-GLI patway components were
4
Department of Pathology, "Victor Babeș" University of Medicine and expressed in androgen-dependent PC cell line LNCaP. Interestingly,
Pharmacy, Timișoara, Romania, 5 Department of Urology, University of androgen-deprived conditions significantly upregulated GLI3.
Medicine and Pharmacy "Victor Babes", Timisoara, Romania Conclusion: Our study has determined an increased activity of HH-GLI
pathway in PC and potential role of GLI3 in androgen-independent
Background & Objectives: The aim of our study was to evaluate some growth. However, its relation to PC progression and mechanisms of sus-
immunohistochemical (IHC) markers which can be of value in determin- taining androgen-independent growth has yet to be determined.
ing tumour depth infiltration in transurethral resection of urinary bladder Observation of higher nuclear localization of GLI3 in higher Grade
tumour (TURBT) specimens. Group could indicate an increased paracrine HH-GLI signalling, from
Methods: Representative sections from 15 cases were selected: 5 cases of tumour cells toward stroma.
urinary bladder tumours with equivocal invasion of the muscularis
propria (MP) diagnosed on TURBT specimens, 5 cases of the normal This study was funded by dm-drogerie markt donation.
urinary bladder wall (UB) obtained from total cystectomy specimens with
other malignancies and 5 cases with normal intestinal wall. The cases
were analysed IHC with Smooth muscle actin (SMA) antibody and PS-17-053
Smoothelin antibody. The positivity of the smooth muscle structures from Differential proteomic profiles in ASCL1-positive prostate cancer
the muscularis mucosae (MM) and MP was assessed. F. Naples1, I. Rapa1, B. Pergolizzi1, C. Barbero1, D. Tota1, A. Rigutto1, E.
Results: The reactivity for Smoothelin in the normal UB cases was: Bollito2, M. Volante1
1
heterogeneous (4moderate, 1weak) in MP and predominantly negative University of Turin, Italy, 2 AUO San Luigi Gonzaga, Orbassano (TO), Italy
in the MM. The staining pattern for Smoothelin in the intestinal wall cases
was: moderate, diffuse (3cases) and weak, heterogeneous (2cases) in the Background & Objectives: Neuroendocrine differentiation (NED) in
MP; negative in the MM. All cases presented a strong and diffuse posi- prostatic cancer is a frequent phenomenon, dynamically induced by an-
tivity for SMA in the MM and MP. Subsequently, the association of SMA drogen deprivation therapy. Over-expression of ASCL1 has been demon-
and Smoothelin antibodies in the equivocal cases facilitated the classifi- strated to be a pivotal mechanisms of NED, but the pathways impaired by
cation of 4cases-pT1 and 1case-pT2. its activation in prostate cancer cells are unknown.
Conclusion: Although the value of the study is limited by the few num- To identify novel protein biomarkers associated with the transcriptional
bers of cases analysed, the association of Smoothelin and SMA can rep- activation of ASCL1 in prostatic cancer.
resent an attractive and useful combination of markers in the interpreta- Methods: LNCaP cell line was transfected with ASCL1 and empty vector,
tion of problematic cases of TURBT specimens. as control. Protein extracts were analysed by bi-dimensional electrophore-
sis and quantitative expression of the protein spots was evaluated with
Supported by the Victor Babes University of Medicine and Pharmacy, PDQuest Advanced software. Differentially expressed proteins were iden-
Timisoara Internal Grant: PII-C5-TC-2017-09 - 771/17.01.2017 tified by mass spectrometry using MALDI ToF. Selected proteins were
Acronym: DISPRoVE. validated by means of immunohistochemistry in a series of 50 prostate
cancer tissues segregated according to levels of ASCL1 gene expression.
Results: 97 proteins were differentially expressed in LNCaP-ASCL1
PS-17-052 transfected as compared to control cells, and 29 additional proteins were
Expression profile and cellular localisation of GLI3 and PTCH1 pro- exclusive of one or the other cell model. Of them, 30 were identified by
teins in healthy and tumour prostate tissue mass spectrometry and regulate a variety of biological processes revealed by
I. Stefanac1, M. Mrcela2, D. Trnski3, M. Sabol3, V. Musani3, P. Ozretić3, means of bioinformatics analysis. In addition, three of them, peroxiredoxin,
S. Levanat3 calreticulin and alpha-enolase were selected for tissue validation according
1
Primary Health Care Center Osijek, Croatia, 2 Medicinski Fakultet to their impact on cancer biology and availability of commercial antibodies
Osijek, Croatia, 3 Division of Molecular Medicine, Ruđer Bošković for immunohistochemistry. In agreement with proteomic data, expression of
Institute, Zagreb, Croatia calreticulin was increased whereas expression of peroxiredoxin and alpha-
enolase was reduced in ASCL1-positive prostate cancer samples.
Background & Objectives: The Hedgehog-GLI (HH-GLI) signalling Conclusion: Our data identified specific proteomic profiles and novel
pathway is primarily associated with embryonic development but its role in tissue biomarkers associated with ASCL1 transcriptional activation in
carcinogenesis has being intensely studied in the last two decades. Recent prostate cancer.
research indicates that HH-GLI pathway could be a key player in prostate
cancer (PC) development and progression, as well as therapeutic resistance. Supported by AIOM (Associazione Italiana Oncologia Medica)
The main objective of this study was to investigate the HH-GLI pathway
activity in PC in comparison with healthy prostate and prostate inflammation.
Methods: Around 30 formalin-fixed paraffin-embedded tissue samples PS-17-054
per group were collected from PC patients (Grade Groups I-V) and two Clear cell sarcoma of the kidney
controls groups (benign prostate tissue and prostate inflammation). R. Narjess1, G. Sahraoui2, R. Doghri3, R. Sellami2, O. Chakir2, K. Mrad3,
Expression profiles of GLI3 and PTCH1 proteins was detemined L. Charfi3, M. Driss3
1
immunohistochemically. The level of protein staining was expressed by Institute of Carcinology Salah Azaïez Institute, Tunis, Tunisia, 2 Salah
multiplying percentage of positive stained cells and staining intensity Azaïez Institute, Tunis, Tunisia, 3 Department of Pathology, Salah Azaïez
(histoscore), separately for prostate epithelium and stroma. Cellular Institute, Tunis, Tunisia
Virchows Arch

Background & Objectives: Clear cell sarcoma of the kidney (CCSK) is Conclusion: No positive correlation was found between PDL-1 expres-
an uncommon malignant paediatric renal neoplasm. It has a propensity sion and the studied demographic and pathological factors, making the
for aggressive behaviour and late relapses. prediction of its expression unlikely. Presence of an UC variant could be
Our aim is to perform a clinicopathological study of CCSK. associated to a positive PDL-1 expression but broader studies are re-
Methods: Retrospective study of 7 cases of CCSK diagnosed at our quired. PDL-1 immunohistochemical status assesment remains impera-
department between January 2005 and December 2018. tive for all patients requiring anti-PDL-1 targeted chemotherapy.
Results: Our series included 4 male and 3 female patients. Mean age was
19 months (6 months-4 years old). This work was supported by the University of Medicine and Pharmacy of
Right kidney was affected in 2 cases, the left in 1 case. In other cases, the Tîrgu Mureș Research Grant number 15609/5/29.12.2017.
side was not specified.
Diagnosis was made on a piece of nephrectomy in 6 cases.
The mean size of these tumours was 13 cm (6.5–24 cm). The cut surface PS-17-056
was heterogeneous, with mucinous glistening appearance and cystic foci, Evaluation of the true incidence of RCC in a large pathology
in 3 cases. department
Histologically, nests or cords of cells separated by regularly spaced fibro- G.E. Olteanu1,2, I. Mihai1, A. Jurescu1, A. Gheju1, D. Herman3, A.
vascular septae was found in 6 cases. Dema3
1
Immunohistochemistry, including vimentin, CD34, cytokeratin, desmin, actin Department of Pathology, University of Medicine and Pharmacy "Victor
and CD99, was performed in 6 cases. Vimentin was positive in all these cases. Babes", Timisoara, Romania, 2 Centre for Gene and Cellular Therapies in
Abdominal lymph node metastases were present in 3 cases and distant Cancer - Oncogen, Romania, 3 Department of Pathology, Emergency
metastases in 2 cases. Tumour recurrence was observed in 2 cases (after Clinical County Hospital "Pius Brinzeu", Timisoara, Romania
2-3 years).
Conclusion: CCSK is notorious for mimicking virtually every other pae- Background & Objectives: Renal cell carcinoma (RCC) has an estimat-
diatric renal neoplasm, particularly nephroblastoma. The importance of ed incidence of approximately 1940 per 100000 people in Romania
distinguishing it from Wilms tumour lies in its poor prognosis. (GLOBOCAN), regrettably, no countrywide database exists to evaluate
Immunochemistry is used to exclude differential diagnosis. Recently, the true incidence of this pathology. The aim of our study was to retro-
molecular biology is regaining its place in the diagnosis of CCSK. spectively evaluate the incidence of renal cell carcinoma diagnoses in our
pathology department over a period of 40 months (01.09.2015 -
01.01.2019) and to provide a starting point in collecting and evaluating
PS-17-055 the true incidence of RCC in Romania.
PDL-1 in urothelial carcinoma: can clinical and pathological factors Methods: Our indexed database was searched for diagnoses of
predict the immunohistochemical expression status? renal cell carcinoma in renal biopsy specimens, tumourectomy,
I.A. Nechifor-Boila1, A. Nechifor-Boilă2, M. Decaussin-Petrucci3, A. partial nephrectomy, and total nephrectomy surgical specimens.
Loghin4, C. Chibelean5, A. Ruffion6, S. Voidăzan7, A. Borda8,9 The age range was established between 20 and 90 years of age.
1
Department of Anatomy, UMFST Targu-Mures, Romania, Exclusion criteria were a diagnosis of non-renal cell neoplasm
2
Department of Histology, UMFST Târgu Mureş, Romania, arising in the kidney and the pathological evaluation of a meta-
3
Department of Pathology, Centre Hospitalier Lyon Sud, Hospices static lesion. Our indexed database was searched for diagnoses of
Civils de Lyon, Universite Lyon 1, Pierre Benite, France, 4 Department renal cell carcinoma in renal biopsy specimens, tumourectomy,
of Histology, UMFST Targu-Mures, Romania, 5 Department of Urology, partial nephrectomy, and total nephrectomy surgical specimens.
Mureș County Hospital, Târgu-Mureș, Romania, 6 Department of The age range was established between 20 and 90 years of age.
Urology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Exclusion criteria were a diagnosis of non-renal cell neoplasm
Universitè Lyon 1, Pierre Bènite, France, 7 Department of arising in the kidney and the pathological evaluation of a meta-
Epidemiology, UMFST Targu-Mures, Romania, 8 Department of static lesion.
Histology, University of Medicine, Pharmacy, Science and Technology Results: In the 40 months of retrospective data examined, 28.820 surgical
Târgu-Mureș, Romania, 9 Department of Pathology, Târgu-Mureș specimens of non-tumour and tumour cases were examined in our pathol-
Emergency County Hospital, Romania ogy department. Out of 28.820 surgical specimens, 726 surgical speci-
mens and biopsies of the kidney (non-tumour and tumour) were selected,
Background & Objectives: PDL-1 (Programmed Death Ligand -1) ex- out of which a total of 65 diagnoses of RCC were identified representing
pression assessment is compulsory for anti-PDL1 chemotherapy in 8.95% of the cases. The results were further stratified based on sex, age,
cisplatin-unfit urothelial carcinoma (UC) patients. We aimed to assess if urban or rural residence, associated pathology, type of surgical specimen,
current clinical and pathological factors could predict PDL-1 status in a and RCC type.
transversal cohort study. Conclusion: Our results provide an opening perspective of the true inci-
Methods: We included 69 patients with radical cystectomy performed for dence of RCC in Romania in a large pathology department-based study
muscle-invasive UC in the Urology Department, Târgu-Mureș County and the prospects and implications of knowing the true incidence of a
Hospital (România) and Urology Department, Centre Hospitalier Lyon malignancy.
Sud (France). PDL-1 status was immunohistochemicaly assessed using
the 22C3 clone (DAKO). The Combined Positive Score (CPS) was ap-
plied with the positive cut-off value set at ≥10. PS-17-057
Results: The majority of patients were men (57/82.6%). Pure classic UC Comparing the performance of three PD-L1 antibodies for PD-L1
was present in 36 cases (52.2%), followed by UC variants (n=33, 37.8%). expression in renal cell carcinoma
PDL-1 CPS score was positive in 28 cases (40.6%). No statistically sig- S. Park1, Y.C. Wi1, S. Shin1, K. Jang1
1
nificant differences were observed between PDL-1 positive, versus PDL- Department of Pathology, College of Medicine, Hanyang University,
1 negative cases in relation to patients’ age (p=0.22), sex (p=0.33), car- Seoul, Republic of Korea
cinoma in situ (p=0.3), positive surgical margins (p=0.13), T (p=0.72), N
(p=0.67) or M stages (p=0.86). However, UC variants were associated Background & Objectives: Immunotherapies targeted against pro-
with a positive PDL-1 expression status (p=0.048), especially the squa- grammed death ligand 1 (PD-L1) and its receptor (PD-1) have
mous variant (p=0.0007), compared to classic UC. improved survival in patients with advanced cancer. PD-L1 protein
 Virchows Arch

expression has emerged as a biomarker that predicts which patients Background & Objectives: Intraluminal inclusions (IIn) are found in
are more likely to respond to immunotherapy. For more effective 30% of prostate cancer (PCa) biopsies.
immunotherapy for renal cell carcinoma (RCC), comparing the Objective: to estimate the influence of IIn on the level of inflammation in
performance of PD-L1 antibodies has been necessary. the PCa tissue.
Methods: Three PD-L1 antibodies (SP142, SP263, and E1L3N) expres- Methods: 30 PCa samples with IIn (prostatic calculi and/or corpora
sions in tumour and immune cells were immunohistochemically evaluat- amylacea) and 30 PCa control samples were used for the study. All sam-
ed in 252 RCC patients. All PD-L1 immunohistochemistry assays were ples were examined histologically (hematoxylin-eosin staining) and by
performed using Ventana Benchmark platforms. Each slide was estimated immunohistochemistry (detection of CD68-positive and MPO-positive
percentage of malignant and immune cells expressing PD-L1. Samples cells). All data was analysed by Shapiro-Wilk test, Mann-Whitney U-test
were defined as a positive when 10% or more PD-L1 expression of and Student’s t-test.
tumour cells and 1% or more of immune cells. Results: Inflammation in PCa tissue was presented as diffuse or focal
Results: Among 252 samples, the SP142 assay was an outlier, with a inflammatory infiltrates. PCa with IIn had 37.48±3.39 SD68-positive cells
significantly lower positive rate in tumour cells (clear cell RCC, 3.3%; in the field of view with diameter 1 mm. Their localization was associated
papillary RCC, 13.6%). The positive rate of E1L3N tests was higher than with IIn. Control PCa samples had 92.14±4.12 (p<0.001) CD68-positive
that of SP263 test in clear cell RCC (SP263, 7.2%; E1L3N, 18.2%). The cells. In the PCa with IIn 31.5±1.71 MPO-positive cells were detected.
positive rate of SP263 tests was higher in papillary RCC (SP263, 68.18%; Their localization corresponded to areas of necrosis and tissue around the
E1L3N, 40.9%). There was no significant difference among three anti- IIn. PCa without IIn had 13.89±1.26 (p<0.001) MPO-positive cells.
bodies expression of immune cells (SP142, 59.1%; SP263, 72.6%; Conclusion: The presence of intraluminal inclusions in the prostate cancer
E1L3N, 71.0%). tissue is accompanied by intense inflammation. This may lead to disease
Conclusion: The assay using the SP142 antibody is detected significantly progression, increased invasive growth and metastasis development.
less PD-L1 expression in tumour cells. The assay for antibody SP263 and
E1L3N showed significantly different staining results among tumour
subtypes. PS-17-060
The micronucleus frequency in urothelial exfoliated cells as possible
additional test for early detection of urothelial cell carcinoma
PS-17-058 A. Podrimaj-Bytyqi1, S. Manxhuka-Kerliu1,2, G. Gashi1,2, L. Shahini1,2,
Review of collecting duct carcinomas in a tertiary hospital: 20 year A. Borovecki3
1
review Faculty of Medicine, University of Pristina, Albania, 2 Institute of
A. Pezzella Risueño1, I. Ruz-Caracuel1, C. Ballesteros1, E. Linares1, E. Pathology, University Clinical Center of Kosovo, Albania, 3 Institute of
Garcia-Fernandez2, P. Gonzalez-Peramato1 Pathology "Enge", Zurich, Switzerland
1
Hospital Universitario La Paz, Spain, 2 Hospital Universitario La Paz,
Argentina Background & Objectives: Bladder urothelial cell carcinoma (UCC) is
an increasingly prevalent cancer worldwide. It has a higher incidence rate
Background & Objectives: Collecting duct carcinoma (CDC) is a rare in men than in women; in people exposed to arsenic, cigarette smoking,
but very aggressive variant of kidney carcinoma. It´s frequency is less alcohol, and so on. Cystoscopy is the gold standard for the detection of
than 1%. Our objetive was to evaluate clinical aspects, histological (up- bladder tumours, followed by urine cytology and the UroVysion™ FISH
dated tp WHO 2016 classification) and immunohistochemical findings in test. Except for cytology, other methods, although they have high detec-
CDC in a tertiary hospital. tion rates, are expensive, time consuming and uncomfortable.
Methods: We reviewed at the Department of Pathology 783 specimens of Methods: Overall forty first-diagnosed and non-smoker patients (men) with
nephrectomy specimens between 1996 and 2017. Seventeen cases were UCC and twenty controls were enrolled in the study. Patients were divided
diagnosed of CDC. After review of all the cases by two expert according to tumour grade in low grade UCC (N=20) and high grade UCC
uropathologists and ancillary studies, 9 were admitted as CDC (1.15%). (N=20), and according to tumour muscle invasion in non-muscle-invasive
Results: Median age was 68 (age range 48-82) years. Average size tu- UCC (N=16) and muscle-invasive UCC (N=24). Micronucleus (MN) assay
mour was 7.4 (5-18) cm. The 50% of the patients had metastatic disease at was used to evaluate the genetic instability levels in urine derived urothelial
diagnosis. After histological review 8 cases were re-classified as papillary cells, expressed as the number of micronucleated cells per 1000 counted
carcinoma (4), urothelial carcinoma (3), morphological fumarate cells. All microscopic slides were analysed by a second observer.
hydratase deficient carcinoma (1). We did immunohistochemistry, and Results: Our results show that the MN frequency in UEC is significantly
all our cases of CDC were positive for PAX-8. higher in patients with UCC than in controls (p<0.001), as well as be-
Of our CDC cases, 4 showed a predominant papillary pattern, the other tween subgroups according to tumour grade (p<0.049) and tumour mus-
cases had a tubular, tubulo-papillary, or tubulocystic morphology with an cle invasion (p<0.044).
invasive ductal pattern and an associated desmoplastic response in the Conclusion: Although further studies are needed for standardization, our
adjacent stroma. findings indicate that the MN frequency in UEC may be a potential
At clinical follow-up all of them had metastasis, the lung the most biomarker for the early detection of bladder cancer and for patient sur-
frecuent organ, followed by liver and bone. veillance. We recommend it as a possible triage-test that might be used
Overall survival after surgery was 7.3 months (1.5-23), 6 patients died of prior to the UroVysion™ FISH testing. This cost-effective method could
cancer related causes, 1 after surgery, 1 unkown and 1 alive. reduce the number of unnecessary tests.
Conclusion: CDC is a very rare, malignant epithelial tumour, with a bad
prognosis. Half our cases had metastasis at diagnosis with an overall The Ministry of Education, Science and Technology of the Republic of
survival of 7 months. PAX8 helps in the differential diagnosis. Kosovo, grant nr: 11/7044, date: 20.10.2014.

PS-17-059 PS-17-061
Intraluminal inclusions in prostate cancer: association with level of Penile squamous cell carcinoma – a 15-year long series with p16
inflammation correlation
A. Piddubnyi1, A. Romaniuk1, R. Moskalenko1 C. Quadros1, D. López-Presa1
1 1
Sumy State University, Ukraine CHULN - Hospital de Santa Maria, Portugal
Virchows Arch

Background & Objectives: Squamous cell carcinoma (SCC) repre- PS-17-063

sents the majority of the malignant epithelial penile tumours. The An immunohistochemical analysis of HIF1 alpha and VEGFR1 in
newest WHO classification of the tumours of the Urinary System high grade T1 bladder cancer
and Male Genital Organs, subclassifies SCC according to HPV A. Ristic-Petrovic1, D. Stokanovic2, S. Stojnev1, M. Potic-Floranovic1, I.
status. We present our casuistic data throughout a 15 year-long Djordjevic1, L. Jankovic-Velickovic1
1
series with p16 correlation. University of Nis, Medical Faculty, Department of Pathology, Serbia,
2
Methods: An experienced pathologist subclassified the specimens of University of Nis, Medical Faculty, Department of Pharmacology,
penile SCC pertaining to the 2004-2018 period, according the WHO Serbia
classification; p16 examination was performed.
Results: A total of 39 specimens were assessed with an average diagnosis Background & Objectives: Hypoxia-inducible factor 1 alpha (HIF1
of 2,4 SCC/year. Age ranged from 35 to 103 years (mean 71 years). The alpha) is known to induce transcription of more than 60 genes, including
non-HPV-related carcinomas were more frequent (79%), with the usual vascular endothelial growth factor (VEGF) and VEGF receptors that are
subtype being predominant (56%), followed by mixed (13%), involved in angiogenesis, which assist in increasing oxygen delivery to
pseudohyperplastic (5%) and verrucous subtypes (5%). The HPV- hypoxic regions of tumour. It has been determined that overexpression of
related carcinomas were led by the warty-basaloid variant (10%), follow- hypoxia-inducible factor 1-alpha (HIF1 alpha), and vascular endothelial
ed by the warty (8%) and the basaloid subtypes (3%). Regarding p16, growth factor receptor 1 (VEGFR1) correlates with tumour grade, recur-
there was 97,4% concordance of HPV-related carcinomas and p16 posi- rence and progression of the bladder cancer, as well as poor overall
tivity - particularly noteworthy is one case of SCC usual type and one survival.
SCC mixed type with sarcomatoid component that showed p16 Methods: The immunohistochemical expression of HIF1 alpha, and
expression. VEGFR1 was evaluated in 135 high grade T1 bladder cancer samples,
Conclusion: The high concordance between p16 status and histological incorporated in tissue microarrays. HIF1-alpha was assessed through nu-
subtyping demonstrates that p16 status is a reliable stratification method clear staining, while for VEGFR1 cytoplasmic expression was declared
that may have diagnostic and prognostic implications, yet, some excep- as positive.
tions to that concordance may punctually be found. Results: After a mean follow-up of 50 months, in 135 patients diagnosed
with high grade T1 urothelial bladder cancer, we found that patients who
had concomitant carcinoma in situ had worse overall survival (p<0.05),
PS-17-062 furthermore, those tumour samples less expressed HIF1 alpha (p<0.05),
Specific miRNA profiles are associated with the development of neu- and VEGFR1 (p<0.05). We found nuclear HIF1-alpha expression to be
roendocrine phenotype in prostate cancer patients undergoing an- an independent prognostic factor for both recurrence-free survival
drogen deprivation therapy (p<0.001) and overall survival (p<0.01) in all high grade T1 samples.
I. Rapa1, C. Barbero1, C. Buttigliero1, S. Izzo1, D. Tota1, F. Naples1, E. Patients with positive VEGFR1 had longer disease-free (p<0.01) and
Bollito2, M. Tucci3, A. Berruti4, G.V. Scagliotti1, M. Volante1 overall survival (p<0.01).
1
University of Turin, Italy, 2 A.U.O. San Luigi Gonzaga, Orbassano Conclusion: Estimation of HIF1 alpha and VEGFR1 expression could be
Turin, Italy, 3 S.C. Oncologia Ospedale Cardinal Massaia, Asti, Italy, diagnostic supplement, selecting the high grade T1 bladder cancer pa-
4
University of Brescia, Italy tients that require an intensive follow-up, especially if concomitant CIS is
present, considering this entity as additional obstacle in treatment high
Background & Objectives: The onset of neuroendocrine differentiation grade T1 urothelial cancer.
(NED) is associated with resistance to androgen deprivation therapy
(ADT) in prostate cancer, but the mechanisms responsible for its dynamic
modulation are unclear. PS-17-064
We analysed in vivo and in vitro the association of miRNA expression Evaluation of two important prognostic factors related to the bio-
with NED as a consequence of ADT in prostate cancer. chemical progression after radical prostatectomy in a series of 530
Methods: 1066 human miRNAs were arrayed in LNCaP cells at basal patients: staging and surgical margins. A study in Brazil
conditions and cultured under androgen withdrawal and in tumour tissue A. Rolim da Paz1, A. Billis2
1
samples before and after ADT, and correlated with the onset of NED after University Hospital Lauro Wanderley/EBSERH/UFPB, Brazil, 2 State
treatment. Tissue samples were grouped as follows: group A, prostate University of Campinas - Unicamp, Brazil
cancer tissues negative for NED after ADT; group B, prostate cancer
tissues developing NED after ADT; group C, pure neuroendocrine pros- Background & Objectives: The data provided by radical prostatectomy
tate cancers, untreated. (RP) on staging (extraprostatic extension - EPE) and surgical margins
Results: Unsupervised cluster analysis of global miRNAs profiling in (SM) allow us to evaluable the risk of neoplasia progression, determined
pre-treatment samples segregated prostate cancer patients according by recurrence/biochemical progression. The objective of this study is
to the presence or absence of NED after treatment, clustering group B correlate the factors related to the morphological findings in the surgical
together with pure neuroendocrine carcinomas (group C), with 218 specimen of RP with the biochemical progression after radical prostatec-
miRNAs differentially expressed between group A and group B. tomy (PSA>=0.2): a) surgical margins (SM) and b) extraprostatic neo-
Global miRNA profiling in matched samples before and after ADT plastic extension (EPE).
showed a significant dynamic modulation of subsets of miRNA in Methods: In this retrospective study, we used the information obtained
group A (38 miRNAs) and B (117 miRNAs), all but one different in from the anatomopathological reports and EXCEL table containing the
the two groups. 27 miRNAs (21 up-modulated and 6 down-modulat- corresponding morphological and clinical-laboratory data of 530 sequen-
ed) were common in group B and in LNCAP cells developing NED tial RP over the 20-year period (1997 to 2017). The statistical study was
under androgen withdrawal, and regulate up to 2500 genes, involved performed through the Kaplan-Meier estimator for the biochemical recur-
in more than 60 pathways. rence time using the Log-Rank test for comparison between groups.
Conclusion: Specific miRNA signatures are associated to the develop- Results: The Kaplan-Meier estimator and the Log-Rank statistical test
ment of NED in prostate cancer undergoing ADT. (p<0.001) showed for both variables that the focal EPE bahaves closer to
the patients without EPE and the focal SM closer to the SM negative
Supported by Fondazione AIOM- Associazione Italiana di Oncologia patients. Both EPE and SM when non-focal behave statistically signifi-
Medica- cant in relation to cases without EPE and SM negative.
 Virchows Arch

Conclusion: This study highlights the importance of the evaluation of surgi- Spain, 15 Medical Oncology Department, Hospital Universitario Marquès
cal margins and staging (EPE) as influencing factors in the biochemical pro- de Valdecilla, Santander, Spain, 16 ICO Josep Trueta, Girona, Spain,
17
gression of prostate carcinoma. It also allows the comparison with internation- Medical Oncology Department, Hospital Virgen de la Salud, Toledo,
al series and construction of guidelines for post-RP prognostic evaluation. Spain, 18 Medical Oncology Department, Hospital Universitario Lucus
Agusti, Lugo, Spain, 19 Medical Oncology Department, Hospital Clínic i
Provincial De Barcelona, Barcelona, Spain, Spain, 20 Epithelial
PS-17-065 Carcinogenesis Group, Spanish National Cancer Research Centre
The features of p53 and Ki-67 expression during Gleason's grade (CNIO), CIBERONC, Madrid; Department de Ciències Experimentals i
increase in prostate cancer de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
M. Lyndin1, A. Piddubnyi2, V. Sikora3, O. Romaniuk4, O. Kravtsova5, A.
Romaniuk4 Background & Objectives: Lynch syndrome (LS) patients develop up-
1
Sumy State University, Medical Institute, Department of Pathology, per tract urothelial carcinoma (UTUC) in 4-6% of cases and urothelial
Ukraine, 2 Sumy State University, Ukraine, 3 Sumy State University, bladder carcinoma (UBC) in 0-5%. Although it is well documented that
Medical Institute, Pathology Department, Ukraine, 4 Sumy State 1-3% of all UTUCs are associated with LS, the frequency of LS among
University, Ukraine, 5 Sumy State University, Department of Pathology, UBC cases is not well known. This study assessed the frequency of
Ukraine, Ukraine mismatch repair (MMR) protein expression loss (as a LS screening test)
in a large series of cases with muscle-invasive UBC (MI-UBC).
Background & Objectives: Prostate cancer is the most common malig- Methods: Review of medical records from 16 Spanish hospitals identi-
nant tumour of the male reproductive organs. Its course depends on the fied 540 muscle-invasive UBC cases. Sixteen tissue microarrays (TMAs)
histological and immunohistochemical characteristics of neoplasias. In were built and immunostained for MSH2, MSH6, MLH1 and PMS2.
view of this, the purpose of study was to investigate the influences of TMAs were built with tumour specimens obtained by either radical
prostate cancer differentiation on peculiarities of Ki-67 and p53 cystectomy without prior neoadjuvant therapy (n=404) or diagnostic
expression. transurethral resection (TUR) (n=136). TMA negativity for PMS2 and
Methods:The research was conducted on acinar prostate cancer cases MSH6 staining was confirmed on whole sections. Two expert patholo-
which were graded according to Gleason Score. The presence of p53 gists (CC, EM) reviewed all slides.
(SP5–1μg/ml) and Ki-67 (SP6–0.5μg/ml) receptors was detected by the Results: Only one out of 536 evaluable UBC cases showed loss of ex-
immunohistochemistry. pression for both MMR proteins. The patient was a 40-year-old man
Results: Immunohistochemically in prostate cancer tissues it was re- whose LS diagnosis (confirmed by sequencing, with a germline MSH2
vealed different p53 and Ki-67 expressions in tumours. Despite the strong mutation) was known at the time of UBC TUR.
correlation between them, they didn't depend on the Gleason's grade. It Conclusion: As shown in the literature, frequency of MI-UBC in the
should be noted, that significantly higher their expression was found in context of LS is very low. Our results indicate that implementation of a
5th Gleason's grade comparing with others. Moreover, in 5th grade group universal LS testing algorithm to detect such an uncommon occurrence is
there are two kinds of tumour tissue: 1. with over-expression of p53/Ki- not necessary in patients with MI-UBC cases. Nevertheless, MMR pro-
67 and significant cellular atypia; 2. with low level of p53/Ki-67 expres- tein expression analysis is recommended for younger patients or those
sion and without cellular polymorphism. suffering from a LS-related condition.
Conclusion: The increase of Gleason's grade in prostate cancer tissue is
not accompanied by the direct enhance of Ki-67 and p53 expression. The
morphological evaluation of cancer tissue should include as Gleason's PS-17-067
grade as cellular atypia due to different expression of these proteins for Incidental prostate adenocarcinoma with prostate transuretral resec-
5th Gleason's grade tumours. tion, 8 years experience
C. Sayar1, S. Ekmekci1, O. Cakmak2, U. Kucuk1
1
Izmir Tepecik Training and Research Hospital, Department of
PS-17-066 Pathology, 2 Izmir Tepecik Training and Research Hospital, Department
Low frequency of mismatch repair protein expression in a series of of Urology
bladder carcinoma
T. Sanhueza1, M.C. Gómez2, E. Musulèn3, A. Font4, N. Malats5, J.P. Background & Objectives: Patients with benign prostatic hyperplasia
Fernández2, J.L. Gago6, E. Grande7, D. Castellano8, M.î Climent9, N. (BPH) and transurethral resection of the prostate (TURP) are able to
Lainez10, M. Sáez11, E. González12, M. Lázaro13, M. Guix14, M. detect incidental early stage prostate cancers (PrCa), which can not be
Lopez-Brea15, N. Sala16, I. Duran15, I. García17, S. Vazquez18, B. detected by clinical examination and / or imaging. In our study, we in-
Mellado19, F.X. Real20, P.L. Fèrnandez2, C. Carrato2 vestigated whether there was a significant difference in the PrCa detection
1
Pathology Department, Hopsital Germans Trias i Pujol, Barcelona, rate, age between tumour detection and non-detection, histopathologic
Spain, 2 Pathology Department, Hospital Germans Trias i Pujol, examination of prostate tissue volume and serum PSA levels after
Barcelona, Spain, 3 Pathology Department, Hospital General de TURP for BPH in our study.
Cataluyna, Barcelona, Spain, 4 Institute Català d'Oncologia, Barcelona, Methods: Between 2011 and 2018, 391 patients who underwent TURP
Spain, 5 Genetic and Molecular Epidemiology Group, Spanish National due to BPH in our hospital were included in the study.
Cancer Research Centre (CNIO), Ciberonc, Madrid, Spain, 6 Urology Results: After histopathological examination, 17 of 391 patients (4.3%)
Department, Hospital Germans Trias i Pujol, Barcelona, Spain, had incidental PrCa. The mean age was 69.5 (26-93) in cases with no
7
Medical Oncology Department, Hospital Universitario Ramón y tumours and the mean age was 74,5 (54-93) in cases with PrCa. When the
Cajal, Madrid, Spain, 8 Medical Oncology Department, Hospital tumours were classified according to age groups, two cases between 50-
Universitario 12 de Octubre, Madrid, Spain, 9 Instituteo Valenciano de 60 years, two between 61-70 years, eight between 71-80 years, 5 cases
Oncología, Valencia, Spain, 10 Medical Oncology Department, Complejo over 80 years were observed. Preoperative serum PSA levels were mea-
Hospitalario de Navarra, Navarra, Spain, 11 Medical Oncology sured and mean PSA level was 5.05 ng / mL in 226 of the non-tumour
Department, Hospital Clínico de Málaga, Málaga, Spain, 12 Medical cases. Pre-operative serum PSA levels of 15 cases with tumour were
Oncology Department, Hospital Morales Messeguer, Murcia, Spain, measured and the mean value was 4.46 ng / mL (0.40-28.5).
13
Medical Oncology Department,Hospital Universitario de Vigo, Vigo, Conclusion: In our study, incidence of incidental PrCa detection (<5%)
Spain, 14 Medical Oncology Department, Hospital del Mar, Barcelona, in TURP materials for BPH was found to be in parallel with the literature.
Virchows Arch

4
In these cases, it was noticed that preoperative PSA levels were lower Department of Pathology, Seoul National University College of
than those of untrained cases. It has been observed that the incidence of Medicine, Republic of Korea
coincidental PrCa detection is higher, especially in patients over 70 years
of age. This is thought to be important in avoiding tumours, especially if Background & Objectives: The importance of programmed cell death
the pre-operative PSA levels and BPH pre-diagnosis were used, especial- ligand 1 (PD-L1) expression has recently emerged in renal cell carcinoma
ly if all of the TURP materials of advanced age were processed. (RCC). The aim of this study was to compare the PD-L1 assays in four
major subtype of RCC.
Methods: We compared PD-L1 expression by two FDA-approved assays
PS-17-068 (22C3 and SP142) and one research use-only antibody (E1L3) in a retro-
Concordance and predictive factors of prostate cancer upgrade and spective cohort of 591 RCC patients. PD‐L1 positivity on the tumour cell
downgrade from multiparametric-magnetic resonance imaging pros- (TC), immune cell (IC), and combined positive score (CPS) was
tate guided biopsy to radical prostatectomy using 2014 ISUP Gleason evaluated.
grade group Results: At a cut-off of ≥ 1%, 132 (22.3%), 120 (20.3%), and 65 (11.0%)
A.Y. Setiasti1, D. van Midden2, C. Hulsbergen van-de Kaa3, J.A. cases stained positively for 22C3, SP142, and E1L3 on IC, respectively.
Schalken4 Meanwhile, 22C3, SP142, and E1L3 expression on TC ≥ 1% was ob-
1
Radboud University Medical Center, Urology Department, served in 24 (4.1%), 12 (2.0%), and 16 (2.7%) cases, respectively. The
Experimental Lab, RIMLS, Nijmegen, The Netherlands, 2 Radboud score of PD-L1 expression between the three assays yielded moderate to
University Medical Center, Pathology Department, RIMLS, Nijmegen, high positive correlation (ρ = 0.599 to 0.835, P < 0.001). The three assays
The Netherlands, 3 Laboratorium Pathologie Oost-Nederland (LabPON), appeared largely similar, although E1L3 was less frequent in staining in
Hengelo, The Netherlands, 4 Radboud University Medical Center, IC. Notably, 22C3 showed highly frequent positivity in TC. PD-L1 ex-
Urology Department Experimental Lab, RIMLS, Nijmegen, pression on TC was positively associated with papillary type 2 RCC (P <
The Netherlands 0.001) and expression on IC was predominantly found in clear cell and
papillary type 1 RCC (P < 0.05). Kaplan–Meier analysis showed a cor-
Background & Objectives: The discrepancy between biopsy and relation between PD-L1 expression on IC and tumour recurrence (P ≤
radical prostatectomy (RP) Gleason score (GS) results remains a 0.001), but not on TC (P > 0.05).
challenge in the management of prostate cancer (PC). The use of Conclusion: The present study shows that expression of PD-L1
multiparametric-MRI prostate guided biopsy (mp-MRGB) may varies depending on the type of antibody and histologic subtype
play role in increasing PC detection and could improve the con- in RCC.
cordance by solving some of the upgrade and downgrade prob-
lems. The study aimed to assess the concordance and to deter- This research was funded by Kitai Kim Charitable Foundation (Seoul
mine the predictors related to upgrade and downgrade occurrence National University Foundation, Inc.) and Seoul National University
between mp-MRGB to RP results using 2014 ISUP GG. Bundang Hospital Research Fund (grant number: 02-2018-015).
Methods: Ninety five eligible patients who performed both RP and
coresponding mp-MRGB prior to RP from January 2006 to December
2014 at Radboud University Medical Center, Nijmegen, The Netherlands PS-17-070
have been selected and reviewed using 2014 ISUP GG. The association Assessment of tumour cells specific features in prostate adenocarci-
of upgrading and downgrading and the predictive factors between mp- noma in correlation with Gleason and Srigley grading systems
MRGB and RP GG were analysed. F. Simionescu1, M. Șerbănescu2, R.M. Pleșea3, V. Ciovica3, M. Bara4, A.
Results: The concordant diagnosis occurred in 51.6% cases. The Stefan5, A. Gradinaru5, M.O. Leavitt6, V.T. Moldovan7, I.E. Pleșea8,7,3
1
downgrade rate (14.7%) was lower than upgrade rate (33.7%). Department of Pathology, University Emergency Hospital, Bucharest,
The discriminative power of upgrade and downgrade models Romania, 2 Department of Medical Informatics and Biostatistics,
showed satisfactory area under ROC curve (AUC) results (up- University of Medicine and Pharmacy, Craiova, Romania, 3 Doctoral
grade=0.747; downgrade=0.867). An upgrade was associated with School, University of Medicine and Pharmacy, Craiova, Romania,
4
increasing pre-operative serum PSA level (OR=1.098; p=0.0005). Department of Pathology, University Emergency Hospital, Bucharest,
Increasing mp-MRG GG (OR=0.379; p=0.002) and total tumour Romania, 5 Themis Pathology SRL, Bucharest, Romania, 6 Leavitt
percentage biopsy cores (OR=0.984; p=0.08) reduced upgrading Medical Inc, Orem, Utah, USA, 7 Department of Pathology, "Victor
possibility. Downgrade was related to increasing mp-MRGB GG Babes" National Institute of Pathology, Bucharest, Romania,
8
(OR=2.363; p=0.001). Increased biopsy cores decreased the down- Department of Pathology, "Carol Davila" University of Medicine and
grade (OR=0.571, p=0.001). Pharmacy, Bucharest, Romania
Conclusion: We concluded that the concordance rate between bi-
opsy and RP was good. The upgrading rate was higher than the Background & Objectives: The aim of this study is to assess the expres-
downgrading. Predictor for upgrading was pre-operative serum sion of some of the main biological behaviour parameters of the tumour
PSA (prostate specific antigen) level. A combination of high bi- cells in correlation with two different grading systems of prostate
opsy Gleason grade and higher percentage of tumour in biopsy adenocarcinoma.
core reduced the upgrade. Sufficient number of biopsy core re- Methods: A series of 435 fields with different patterns of prostatic ade-
duced the downgrade. nocarcinoma according to Gleason (GlS) and Srigley (SgS) grading sys-
tems were selected and immunomarked on four serial sections with:
MMP9, MMP2, E-CAD and PTEN in order to assess: the capacity to
PS-17-069 degrade extracellular matrix, intercellular adhesion and aggressiveness
Comparative analysis of programmed cell death ligand 1 (PD-L1) degree. Images were assessed through a proprietary computational algo-
assays in renal cell carcinoma rithm that marked the pixel where the red channel was more intense than
B. Shim1, K.S. Lee1, S. Yun2, K. Lee3, S. Moon1, G. Choe1,4 the other channels. Then the overall colour intensity of the previously
1
Department of Pathology, Seoul National University Bundang Hospital, selected mask was inverted and considered as the value for the intensity
Republic of Korea, 2 Department of Diagnostic Pathology, Samkwang of the IHC staining, larger values meaning more intense staining.
Medical Laboratories, Republic of Korea, 3 Department of Pathology, Results: MMP9 and MMP2 expressions were almost constant irrespec-
Kangwon National University Hospital, Republic of Korea, tive the degree of differentiation in both systems, the former having
 Virchows Arch

around twice higher values than the latter. E-CAD had a smooth descend- PC architecture change in the broader sense observed morphologically visible
ing trend towards poor differentiated patterns, more pronounced in SgS. Gleason score progression.
PTEN expression was almost constant, irrespective the degree of differ- Methods: We used a tumour model on the entire tissue cut of tumour
entiation. However, there was a direct correlation between MMP9 and E- tissue and tissue microarrays obtained by radical prostatectomy.
CAD, MMP9 and PTEN, MMP2 and E-CAD, and E-CAD and PTEN Quantitative analysis of immunohistochemically detected Crypto-1 was
and no correlation between MMP9 and MMP2 and MMP2 and PTEN performed. For descriptive analysis of microenvironment CD34, CD68,
expressions irrespective the degree of differentiation. CD206 and VEGF were used.
Conclusion: Our results suggest that expressions of tumour cells behav- Results: Preliminary data evaluation showed statistically significant cor-
iour parameters correlated with each other in almost all cases, but not with relation (p< 0.01) of Crypto-1 immunohistochemical expression with
the degree of differentiation irrespective of grading system. progression from non-malignant – prostatic intraepithelial neoplasia
(PIN)-adenocarcinoma; correlation of Crypto-1 expression and TAMs
of M1 phenotype and in the group of adenocarcinoma with leading
PS-17-071 Gleason pattern (p<0.05), respectively.
Primary urethral clear cell carcinoma: clinical and pathologic Conclusion: Study showed that Crypto-1 assures more precise detection
implification and characterisation of molecular aberrations of poorly differentiated and undifferentiated subpopulations of cells that
B. Song1 are gaining properties similar to embryonic and stem cells. Therefore,
1
Kangbuk Samsung Hospital, Republic of Korea future targeting signalling pathway Crypto-1 has potential to become an
attractive target for unresponsive cancer cases treatment.
Background & Objectives: Primary clear cell carcinoma of the urethra
is very rare and known to occur predominantly in women. It has been
reported to have poor prognosis with low 5-year survival. A number of PS-17-075
clinicians and pathologists may be unfamiliar with this rare entity. And Prostate cancer in young adults
even molecular abberations of this rare neoplasm has not yet been fully S. Teoran1, A. Dema2, R. Bardan3, L. Daminescu3, A. Cumpanas3, B.
studied. In this study, we presented clinical, histopathlogical findings and Suciu1
1
molecular characteristic of this rare neoplasm. Spitalul Clinic Judetean de Urgenta "Pius Brinzeu" Timisoara,
Methods: A total of 5 cases diagnosed as primary clear cell carcinoma of Romania, 2 Department of Pathology, Emergency Clinical County
the urethra was included. We assessed immunohistochemical profile and Hospital "Pius Brinzeu", Timisoara, Romania, 3 Spitalul Clinic Judetean
the mutational spectrum of the neoplasm evaluated by whole exome de Urgenta "Pius Brinzeu" Timisoara/"Victor Babes" University of
sequencing (WES). Medicine and Pharmacy, Romania
Results: All 5 patients were female and the mean age of the patients was
61.8 yrs. Two of these patients had history of breast cancer. Background & Objectives: Prostate cancer represents the appanage of old
Immunohistochemical staining revealed CK7 and PAX8 strong positivity age, the majority of patients with this neoplasia being diagnosed between the
and CK20, PSA, ER, PR negativity with variable SMAD4, p53 and Ki-67 ages of 70 and 80 years old. However, the number of young adults diag-
index. nosed with prostate cancer has increased during the last two decades.
The molecular abberation analysed by whole exome sequencing was The present paper aims to analyse, from the perspective of some clinical
variable and revealed no overlapping common mutation between pa- and morphological characteristics, prostate cancer in young men.
tients. Genetic alteration of PBRM1, LAMC2, KRAS, KEAP1, Methods: The Pathology Department of SCJUPBT database provided
AMER1, PIK3R, ARID1A, NKD1, CAPN2, CHD4 were identified. the cases of prostate cancer corresponding to the following inclusion
Germline mutation of BRCA gene was not found in two cases with criteria: patients under the age of 55, histopathological diagnosis in our
concurrent breast cancer. department; the cases with secondary involvement of the prostate were
Conclusion: In this study, primary urethral clear cell carcinoma showed excluded. For the selected cases, the following data was collected: age,
diverse mutational spectrum and no common pathogenic mutation. Gleason score, the specimen on which the diagnosis was established,
Futher studies of molecular characteristics is needed to advance our un- PSA levels and other relevant data.
derstanding of the pathogenesis of the neoplasm. Results: 23 patients that correspond to the study’s inclusion criteria have
been identified, with ages between 48 and 55 years old (average age of
53.3). The average PSA level was 169 ng/ml, ranging from 4.2 ng/ml to
PS-17-072 1971 ng/ml. 19 cases were diagnosed in core-needle biopsy, 2 in prosta-
Crypto-1 in the microenvironment of the prostate cancer tectomy specimens and 2 in transurethral resection specimens. The cases
S. Stifter1, F. Grizzi2, A. Cescato3, M. Crncic4, E. Ahel4, G. Dordevic5 had Gleason scores between 6 and 10 (average score of 7.8).
1
Department of Pathology, Clinical Hospital Centre Rijeka, Croatia, Conclusion: The number of prostate cancer cases in young men had an
2
Humanitas Clinical and Research Center, Milano, Italy, 3 Laboratori ascending trend in the analysed period. Our results suggest that prostate
Riuniti Trieste, Italy, 4 Medri UNIRI, Croatia, 5 Department of cancer in young adults represents an aggressive neoplasia, which imposes
Pathology Medial Faculty , University of Rijeka, Croatia a revision of the diagnosis strategy and adapted management.

Background & Objectives: Goal was to investigate the cancer cells micro-
environment in prostate cancer (PCa) to target molecular marker Crypto-1, PS-17-076
which might have been potentially significant in PC progression. Crypto-1 is Application of Raman-fluorescence spectroscopy for diagnosis of
among the embryonic genes that regulate the function of stem cells and is prostatic cancer
found to be over-expressed in human tumours. Immunosuppressive tumours S. Avraamova1, N. Aleksandrov1, S. Timofeev2, Y. Kirillov3
1
associated with macrophage (TAMs) are associated with poor clinical out- I.M. Sechenov First Moscow State Medical University, Russia, 2 City
comes. The function of macrophage against antitumour phenotypes and im- Hospital of Moscow #40, Russia, 3 Tyumen State Medical University,
mune response in the prostate microcirculation remain to be further elucidat- Russia
ed. Further investigation of macrophage polarization status in the prostate
microcirculation and its colocalization within the angiogenic properties of Background & Objectives: Evaluate the effectiveness of the Raman-
tumour neovascularization and Crypto-1 were analysed. We assume that fluorescence spectroscopy method for the diagnosis of prostate cancer
crosscutting multiple path activation could be responsible for progression, (PC).
Virchows Arch

Methods: The prostate gland or fragments were removed from 64 pa- Background & Objectives: Mast cells (MC) are found in various tumour
tients during a radical prostatectomy or transurethral resection because the types, but their pro or antitumoural role in prostate carcinoma is still
suspicion on cancer or benign prostatic hyperplasia. Before carrying out a debated. There are divergent opinions regarding MC correlation with
histological study, Raman-fluorescence spectroscopy of tumour tissue prognostic factors. There are also contradictory findings regarding corre-
samples was performed. InSpectr R532 software and hardware complex lations between MC number and Gleason score (GS) in needle biopsy
was used. samples and radical prostatectomy. Our aim was to evaluate the MC
Results: Spectral characteristics of samples with benign hyperplasia (n = distribution and its correlation with prognostic factors.
25) characterised by the maximum intensity (>40000 AU) of fluorescence Methods: Ninety patients who underwent transurethral resection of the
at a 550 nm wavelength due to oxidized flavoproteins. Tissue samples prostate (TURP) at Colentina Clinical Hospital between 2016-2018 were
affected by a malignant tumour (n = 39), differed by the intensity of selected for this study. We generated multi-tissue blocks and stained mast
fluorescence both in high and low intensity regions (25 to 80 000 AU) cells immunohistochemically with tryptase. We evaluated the mast cells
depending on the degree of tumour differentiation, and characterised by infiltrate density in peritumoural and intratumoural areas and correlate the
the presence of porphyrins (600 nm). Tumour was confirmed in 93,7% by data with GS.
traditional histological and immunohistochemical study. Results: The ages of patients ranged from 53 to 91 (median 71 years).
Conclusion: The results of the investigation showed that Raman fluores- There was no correlation between age and MC count. We found that
cence spectroscopy can be used as an accurate and early method of pros- higher MC counts correlate with lower prognostic group (p<0.05), similar
tate cancer detection. Being safe and inexpensive, RFS is used on-line and to studies conducted on prostatectomy and in contrast with needle biopsy
takes only several minutes. It enables to interactively identify tumourous samples. We found a difference in MC counts from intratumoural areas
regions pre- and intraoperative and define the volume of surgical inter- comparative to peritumoural areas. GS was negatively correlated with
vention with maximum precision. intratumoural MC number (p<0.001).
Conclusion: Higher MC number correlates with better prognosis
suggesting that MC can be a reliable prognostic marker in pros-
PS-17-078 tate cancer. Differences in MC number in needle biopsy versus
Correlation between CD 10 and TIMPs expression in urothelial blad- prostatectomy and TURP may be due to smaller stromal areas
der carcinoma on TUR-V specimens identified in the biopsies. MC may play a role in the relationship
L. Tutuianu1, L. Nichita1,2, M. Cioplea3, A. Vrâncianu3, V. Mitroi3 between stromal microenvironment and tumour cells and can be a
1
Colentina Clinical Hospital, Bucharest, Romania, 2 "Carol Davila" potential target of effective antitumour strategies.
University of Medicine and Pharmacy, Bucharest, Romania, 3 Colentina
Clinical Hospital, Romania
PS-17-080
Background & Objectives: Prognosis in urothelial bladder carcinoma Evaluation of angiogenesis in benign prostatic hyperplasia and pros-
depends on the histological grade and stage of the tumour at diagnosis; tatic carcinoma, with correlations to Gleason Score
however these parameters are difficult to appreciate on TURV specimens A. Vrancianu1, A. Vilaia2, L. Tutuianu3, D. Costache1, M.D. Cioplea3,4,
and there are no reliable parameters predicting the risk of progression or L. Sticlaru3, V. Mitroi3, L. Nichita3,4
1
recurrence. The aim of this study is to evaluate CD10 and TIMPs markers Pathology Department, Colentina University Clinical Hospital,
expression in urothelial bladder carcinoma and correlate their Bucharest, Romania, 2 Colentina Clinical Hospital, Bucharest,
imunnohistochemistry intensity with histological grade and tumour staging. Romania, 3 Colentina Clinical Hospital, Bucharest, Romania, 4 "Carol
Methods: We examined retrospectively 96 TURV specimens submitted Davila" University of Medicine and Pharmacy, Bucharest, Romania
in our department (we selected 48 non-invasive, low grade carcinomas
and 48 infiltrating high grade carcinomas). Multitissue blocks (which Background & Objectives: Prostate cancer is the second most common
incorporated 6 specimens /block) were prepared and slides were cancer worldwide and tumour growth is strongly related to angiogenesis.
immunohistochemically stained for CD10, TIMP 1, TIMP 2 and TIMP 3. The aim of this study was to evaluate the correlation between stromal and
Results: Non-invasive low grade cases were negative or showed focally tumoural VEGF expression, microvessel density (MVD) and the severity
CD10 stromal positivity. Tumour cells were also negative or showed of prostatic carcinoma (PCa), and whether these can differentiate it from
positivity in rare cells. All cases of infiltrative, high grade cases showed benign prostatic hyperplasia (BPH).
CD 10 positivity in both stromal and intratumoural compartment. Methods: We reviewed 90 transurethral prostatic resection specimens –
TIMP 1 showed both stromal and intratumoural positivity with a signif- 45 cases PCa, 45 cases BPH. We performed immunohistochemistry for
icant difference in staining between the two lots (more intense in infiltra- VEGF and CD34 and recorded the Gleason score (GS), prognostic group
tive high grade carcinomas). and investigated the correlation between them. MVD was measured in
TIMP2 and TIMP3 expression were inconclusive. intratumoural, peritumoural and non-tumoural stromal areas (three high-
Conclusion: CD 10 and TIMP1 expression in urothelial bladder carcino- power fields/area). We evaluated the intensity of stromal and tumoural
ma correlates with histological grade and their detection in routine spec- VEGF expression.
imens may improve estimation of individual prognosis. Results: The BPH resection specimens were slightly larger than those
with PCa -27g and 20g, respectively, on average-, from patients aged
between 57-91 years (median age-73).
PS-17-079 Most cases with high GS presented prominent VEGF expression in the
Mast cells in prostate cancer: potential prognostic marker? tumour areas.
A. Vilaia1, A. Vrancianu2, A. Toma3, A.I. Savin4, M. Cioplea5,4, C. Specimens with PCa showed tumour positivity for VEGF more frequent-
Socoliuc2,6, V. Mitroi2, L. Nichita2,7 ly than BPH (most PCa showed strong positivity, whereas BPH cases
1
Colentina Clinical Hospital, Bucharest, Romania, 2 Colentina Clinical showed at most moderate positivity). 25% of BPH and 75% of PCa were
Hospital, Bucharest, Romania, 3 Pathology Department, Colentina negative for VEGF in the stroma.
University Clinical Hospital, Romania, 4 Colentina University Hospital, CD34 immunohistochemical stain revealed increased MVD correlated to
Pathology Department, Bucharest, Romania, 5 Carol Davila University of GS, especially in peritumoural areas. In BPH nodules, MVD was higher
Medicine and Pharmacy, Bucharest, Romania, 6 "Carol Davila" than in PCa.
University of Medicine and Pharmacy, Bucharest, Romania, 7 "Carol Conclusion: The present findings may support the assumption that
Davila" University of Medicine and Pharmacy, Bucharest, Romania VEGF could be significant in predicting the PCa, as well as the MVD.
 Virchows Arch

Moreover, VEGF expression level showed intense staining in cases with Outpatient Clinic № 6, Belarus, 5
Minsk Consulting and Diagnostic
higher GS, which reveals its importance as prognostic marker. Center, Belarus

Background & Objectives:Intraductal proliferation in form of cribri-

PS-17-081 form structures can be found in intraductal carcinoma (IDC) and prostatic
Large nested variant of urothelial carcinoma: a prime example of a intraepithelial neoplasia (PIN). The aim of the study was to establish
FGFR3-mutated, luminal tumour expression of PTEN, AMACR, ERG, p53, chromogranin А (ChrA), an-
V. Weyerer1, M. Eckstein2, E. Compèrat3, H. Juette4, Y. Allory5, R. drogen (AR) and estrogens (ERa and ERß) receptors, aromatase (Arom),
Stoehr6, B. Wullich7, M. Roupret8, A. Hartmann6, S. Bertz9 adhesion molecules (E Cadherin, ß-catenin, CD44), growth factors
1
Insitute of Patholoy, University Hospital Erlangen, Friedrich-Alexander (TGF-ß, EGFR and VEGF), proliferation (Ki-67, CyclinD1, TopoIIα)
University Erlangen, Germany, 2 Institute of Pathology, University and apoptotic (Bax, Bcl2) markers in the cribriform pattern of the IDC
Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, and PIN.
Germany, 3 Hôpital Tenon, HUEP, Sorbonne University, Paris, France, Methods: The material under study comprised 90 radical prostatectomy
4
Institute of Pathology, Ruhr-University Bochum, Germany, specimens (including 30 specimens of IDC adjacent to invasive adeno-
5
Department of Pathology, Hôpital Foch, Universitè Versailles-Saint- carcinoma and 60 specimens of PIN located remotely from cancer). U-
Quentin-en-Yvelines, Universitè Paris-Saclay, Suresnes, France; test was applied, p<0.05.
Institute Curie, CNRS, UMR144, Paris, France, 6 Institute of Pathology, Results: In IDC сytoplasmic PTEN loss was found in 93% of
University Hospital Erlangen, Friedrich-Alexander Universität Erlangen- cases (28/30) and expression of ERG in 67% (20/30). In PIN
Nürnberg, Germany, 7 Department of Urology and Paediatric Urology, no cytoplasmic PTEN loss was found, whereas ERG expression
University Hospital Erlangen, Friedrich-Alexander Universität Erlangen- was found in 7% of cases (4/60). In the cribriform foci of IDC
Nürnberg, Germany, 8 Service d'Urologie, Hôpital La pitiè- Salpetrière, the expression of AMACR (p <0.001), p53 (p=0.026), ERa
Sorbonne University, Paris, France, 9 Institute of Pathology, University (p=0.023), Arom (p=0.015), TGF-ß (p <0.001), EGFR (p
Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, <0.001), Ki-67 (p=0.0016), CyclinD1 (p <0.001) and Topo IIα
Germany (p=0.018) was significantly higher than in PIN. Reduced expres-
sion of AR (p=0.0016), Erß (p<0.001), E-Cadherin (p=0.007), ß-
Background & Objectives: Urothelial carcinoma (UC) of the bladder catenin (p<0.001) and Bax (p<0.001) was also found in IDC. No
may present with distinct histomorphological features and rare histologic difference in expression of ChrA, CD44, VEGF, Bcl2 was found
subtypes have been defined. Since 2016 large nested urothelial carcinoma between the cribriform patterns of IDC and PIN.
(LNUC), has been included within the World Health Organization Conclusion: The cribriform pattern of IDC and PIN differ reliably
Classification among the nested type UC. Little is known about LNUC. by the level of expression of PTEN, ERG, AMACR, p53, ERa,
However, the very limited reports with mainly small case numbers con- Arom, TGF-ß, EGFR, Ki-67, CyclinD1, TopoIIα, AR, Erß, E-
firm the fully malignant and life-threatening behaviour despite the bland Cadherin, ß-catenin and Bax, which may prove significant for
morphological appearance. In this study we evaluatedFGFR3mutational differential diagnosis and for explanation of the aggressive bio-
status as well as the molecular subtype of this specific variant by using a logical nature of IDC.
simplified panel of immunohistochemical markers.
Methods: 26 cases diagnosed as LNUC were collected and
histomorphologically reevaluated. DNA was extracted after manual mi- PS-17-083
crodissection of the tumour, including separation of morphologically dis- Comparison of morphological examination techniques for surgical
tinct areas. SNaPshot analysis of the hot spot regions of the FGFR3gene material from radical prostatectomy in staging and prognosis of
was done. Immunohistochemical basal and luminal markers CK14, CK5, prostate cancer
CD44 FOXA1, GATA3, CK20 and Uroplakin were tested to elucidate the V. Zakharava1, T. Liatkouskaya1, E. Cherstvoy1, A. Muradkhanau1, N.
molecular subtype. Rudishkin1, L. Sagalchik2
1
Results: Of 26 cases eight were pure LNUC, 12 showed an additional Belarusian State Medical University, Belarus, 2 Urology Center of
exophytic (non-invasive) papillary component, four presented areas of Minsk Municipal Outpatient Clinic № 6, Belarus
classical nested type variant and three a component of conventional
UC. 7/7 evaluable pure cases were FGFR3-mutated. 8/10 LNUC with Background & Objectives: Screening measures aimed at certain
papillary component were mutated in both areas. No mutations were types of cancer undertaken in the course of last years resulted
found in 3/3 LNUC combined with classical nested type UC. LNUC in considerable increase in prostate cancer (PCa) detectability.
cases showed predominantly high protein expression levels of luminal Current protocols of morphological examination of biopsy and
markers. surgical specimens from PCa patients include a number of prog-
Conclusion: LNUC either pure or combined with a papillary component nostic parameters, informativeness of which may decrease depend-
is a prime example of a luminal, FGFR3mutated tumour. However, ing on the technique of morphological examination.
LNUC combined with classical nested type UC seems to represent a Objective: Assessment of informativeness of morphological char-
different molecular pathway. Regarding the unique molecular features acteristics of PCa depending on the method of radical prostatec-
our findings are of particular interest since FGFR-pan inhibitors are cur- tomy sampling.
rently tested in clinical trials. Methods: Surgical material from 111 patients having undergone
radical prostatectomy (RPE) was investigated. PCa staging was
based upon the рTNM classification of prostate carcinomas (8th
PS-17-082 Edition TNM), and the tumour histological type was determined
Expression of molecular biomarkers in the cribriform pattern of based on the WHO classification of prostate gland tumours
prostate cancer and PIN (WHO, 2016). The data were processed using the Statistica 8.0,
V. Zakharava1, T. Liatkouskaya1, E. Cherstvoy1, I. Masansky2, M. р<0.05.
Ivanovskaya3, L. Sagalchik4, S. Kuralenya5 Results: All the prostate cancer cases included into this study were
1
Belarusian State Medical University, Belarus, 2 Minsk Municipal Center those of various grades of acinar carcinoma (ISUP GG1 – 30.7%,
for Clinical Oncology, Belarus, 3 Belarusian Medical Academy of GG2 – 36.8%, GG3 – 19.3%, GG4 – 6.2%, GG5 – 7%) with local
Postgraduate Education, Belarus, 4 Urology Center of Minsk Municipal stage prevailing (рТ2с – 62.3%, рТ3а – 19.3%, pT3b – 18.4%).
Virchows Arch

Two techniques of prostatectomy sampling were used within the medical history and the circumstances of death have been suggestive of
framework of this study: that of partial sampling of the material aminophylline-related and carbon monoxide toxicity, respectively.
from the prostate base, its middle third (mostly in the are on visu-
ally detectable prostate cancer) and the prostate apex and the tech-
nique of complete sectioning of RPE. A direct relationship has PS-18-002
been revealed between the volume of the material under study Umbilical cord hemangioma - case report
and the probability of detecting extraprostatic extension (focal C. Amalinei1, D. Bulgaru Iliescu2,3, L. Riscanu2,3, A. Grigoras4
and non-focal EPE ρ=0.31 и ρ=0.34 respectively, bladder neck 1
"Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania,
invasion ρ=0.32 и SVI ρ=0.22) and positive margins (multifocal 2
"Grigore T. Popa" University of Medicine and Pharmacy, Romania,
PMs ρ=0.27, including posterolateral surface ρ=0.18* and prostate 3
Institute of Legal Medicine Iasi, Romania, 4 Department of
base ρ=0.15). Dispersion analysis also showed a significantly Morphofunctional Sciences I-Histology, "Grigore T. Popa" University
higher proportion of cases of EPE and PMs in the group of pa- of Medicine and Pharmacy, Iasi, Romania
tients, where the RPE material was submitted to complete section-
ing, р<0.05. The number of cases with a positive surgical margin Background & Objectives: Umbilical cord hemangioma is a very rare
was low, with predominant localization in the apex region (55%) entity and may be missed during prenatal investigation. This tumour tends
and posterolateral surface of the prostate (25%, mostly in the zone to occur at the placental end of the cord and may arise from one or more
of EPE), and also the bladder neck (15%) and SVI (5%). umbilical vessels. It should be considered in differential diagnosis with
Conclusion: Notwithstanding the fact that the technique of com- other umbilical masses because it may result in significant morbidity. We
plete sectioning of RPE material enhances dramatically the work- report a case of an umbilical cord hemangioma associated with
load of the pathology service, it makes it possible to increase chorangiosis in a stillborn, of 41 weeks gestational age.
detectability of рТ3а stage of PCa and, accordingly, to optimise Methods: Tissue fragments have been harvested in autopsy for micro-
the management of this category of patients. The parameters of scopic examination. Routine hematoxylin-eosin (HE) and trichrome
the PMs, which are subject to morphological evaluation, in turn Masson staining have been performed.
provide an opportunity of improving the surgical technique for the Results: Autopsy revealed the presence of a cerebral edema, along with
most problematic locations and also of securing personalised ap- kidney, heart, thymus, liver, and adrenal gland hyperemia. Lung parenchy-
proach to management of patients with prostate cancer in the ma revealed capillary congestion associated with foetal squames in alveolar
postoperative period. spaces, along with alveolar and interstitial hemorrhages. Microscopically,
chorangiosis associated with fibrinoid deposits, syncytial knots, and
intervillositary haemorrhages have been noticed in the placenta.
Wednesday, 11 September 2019, 09:30 - 10:30, Agora 3 Umbilical cord sections revealed a proliferation of large vascular spaces
PS-18 | Autopsy Pathology lined by endothelial cells and foci of haemorrhages in Wharton's jelly.
Conclusion: A high perinatal morbidity rate is associated with hemangi-
omas of the umbilical cord due to impaired umbilical circulation. This
PS-18-001 condition may be correlated to premature delivery, severe foetal haemor-
Drug-related and toxic myocarditis - histopathologic findings rhage, intrauterine growth restriction, and intrauterine death, as reported
C. Amalinei1, V. Jitaru2, A. Grigoras3, L. Riscanu4,2 in the current case. The differentials with varices, aneurysms, thrombosis,
1
"Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania, and tumours need a careful examination of representative and adequate
2
Institute of Legal Medicine Iasi, Romania, 3 Department of number of samples.
Morphofunctional Sciences I-Histology, "Grigore T. Popa" University
of Medicine and Pharmacy, Iasi, Romania, 4 "Grigore T. Popa"
University of Medicine and Pharmacy, Romania PS-18-003
Seronegative autoimmune encephalitis presenting with a new-onset
Background & Objectives: Myocarditis is a relatively frequent diagno- refractory status epilepticus: a post-mortem study
sis in forensics. Beside idiopathic (viral) and infectious myocarditis, hy- J. Duarte Santos1, H. Pereira1, L. Bento2, A. de Sousa3, C. Pontinha1, M.
persensitivity, drug-induced, and toxic variants may be relatively rare in Honavar4, M. Melo-Pires5, R. Taipa5
1
practice. The aim of our study is to report two necroptic cases, one being Serviço de Anatomia Patológica, Centro Hospitalar Universitário de Lisboa
referred for multidrug voluntary intoxication, in a 44 years-old man, with Central, EPE, Lisboa, Portugal, 2 Unidade de Urgência Mèdica, Centro
a history of toxic liver cirrhosis, mitral failure, alcoholic cardiomyopathy, Hospitalar Universitário de Lisboa Central, EPE, Lisboa, Portugal,
3
and secondary pulmonary hypertension and the second beeing a 90 years- Serviço de Neurologia, Centro Hospitalar Universitário de Lisboa Central,
old female who has been suspected of accidental carbon monoxide EPE, Lisboa, Portugal, 4 Pathology Department - Hospital Pedro Hispano,
intoxication. Portugal, 5 Neuropathology Unit and Portuguese Brain Bank, Centro
Methods: Routine hematoxylin-eosin and Masson’s trichrome stainings Hospitalar Universitário do Porto, Porto, Portugal
have been performed.
Results: Microscopy revealed, in the first case, a drug-related myocardi- Background & Objectives: Autoimmune encephalitis can be triggered
tis, exhibiting a predominant mononuclear inflammatory infiltrate, corre- by infections, paraneoplastic disorders or it may be idiopathic, and pres-
l a t e d w i t h r e n a l n e p h r o t o x i c i t y, a s s o c i a t e d w i t h b e n i g n ent by variety of clinical manifestations, which can be acute or subacute.
nephroangiosclerosis and nephrocalcinosis, along with hepatotoxicity, We report the case of a 53-year-old patient, with no history of epilepsy or
on a background of liver cirrhosis, in the context of Aminophylline vol- other neurological disorder, presenting with acute onset aphasia and dis-
untary intoxication. Toxic myocarditis, exhibiting a mixed inflammatory orientation that rapidly evolved to altered mental status, generalized
infiltrate, containing frequent neutrophils, on a background of coronarian tonic-clonic seizures, respiratory difficulty and evolving to refractory sta-
atherosclerosis and ischaemic myocardial fibrosis, along with an inciden- tus epilepticus, prompting admission to the intensive care unit.
tal thyroidian papillary carcinoma, follicular variant have been diagnosed Methods: The patient had a personal history of essential thrombocythemia
in the second case. and insulin-treated diabetes mellitus. Following extensive investigation, vas-
Conclusion: The diagnosis of myocarditis is of great relevance, since the cular, paraneoplastic, infectious and metabolic aetiologies were excluded.
histopathological features may favour drug-related or toxic myocarditis Cerebral CT and MRI, and cerebrospinal fluid analysis were normal. Serum
against other common conditions, such as infections. In our reports, the and CSF evaluation of neuronal cell-surface antibodies (NMDA, AMPA,
 Virchows Arch

GABA, VGKC) was negative. Thyroglobulin antibodies and thyroid peroxi- Background & Objectives: Features of the origin and cytophysiology of
dase antibodies were elevated in serum and negative in the cerebrospinal fluid. melanocytes are of increased interest. In clinical practice, there is a high
Results: Despite aggressive immunomodulatory treatment there was no mortality rate from melanomas due to their early metastasis and difficul-
clinical improvement and after 46 days the patient died of a medical ties associated with their diagnosis.
condition (septic shock). The main findings of the post-mortem neuro- Objective: to follow the growth dynamics of the number of melanocytes
pathologic examination were inflammatory lesions, namely microglial in different age groups.
nodules, distributed in the limbic region (hippocampus, entorhinal cortex Methods: The study was performed on 30 autopsy samples no later than
and periamygdaloid cortex) and brainstem, particularly in the pons. No 15 hours after death: a fragment of the hairy scalp of women was studied
inclusions suggestive of viral infection were identified. from 15 weeks of gestation to 50 years, the preparations were stained with
Conclusion: Although the patient had high serum thyroid autoantibodies, H&E. The number of melanocytes in each of the 30 hair follicles (HF) of
the lack of response to high-dose corticosteroid therapy along with the one autopsy sample was counted.
neuropathological examination favour the diagnosis of seronegative lim- Results: In HF the number of melanocytes was min. 2.6±0.6 shit per
bic and brainstem encephalitis and do not support the hypothesis of bulb(p<0.005). In postnatal ontogenesis, this indicator increased by
Hashimoto’s encephalopathy. We highlight the importance of neuropath- 10.1±1.9 units in adolescents(p<0.01) and women 20–25 years old 18.5
ological examination in refractory status epilepticus and further CSF ±1.6(p<0.01). However, in women 48-60 y.o., the number of melanocytes
studies are still being performed. decreased to 6.6±0.9 (p<0.005). At the same time, the number of mela-
nosomes in melanocytes and their surrounding keratinocytes decreased.
In the skin of the foetus the hair had a downy structure, but even this type
PS-18-004 of hair had melanocytes with melanosomes.
Previously undiagnosed malignant tumours found in adult autopsy: Conclusion: Age-related changes in the quantitative composition of me-
a 12-year retrospective study lanocytes in the hair follicles were established. The maximum number of
F. Galante Pereira1, A. M. G. Pereira1, C. A. Padrao1, J. Palla Garcia1, R. melanocytes was noted in the period of 20-25 years. Already the 15-week
S. S. Oliveira1 foetus has melanocytes with melanosomes. This study showed that the
1
Hospital Prof. Doutor Fernando Fonseca, EPE, Portugal content of melanocytes in the hair follicles of the scalp of women changes
in ontognosis. Since there has been a rise in the number of melanocytes,
Background & Objectives: Autopsy is a valuable tool in evaluating the question remains: from which cell sources do new melanocytes come
diagnostic accuracy in oncologic disorders. Many studies have drawn from?
attention to the level of concordance between the clinical evaluation
and the autopsy diagnosis of neoplasia. Our purpose was to determine
the incidence of unsuspected neoplasia, the concordance of the clinical PS-18-006
evaluation and neoplasia, and the concordance of previous histologic Pseudocarcinomatous hyperplasia of the lung: a pathological diag-
diagnosis with neoplasia that were present in autopsies. nostic challenge
Methods: A retrospective, 12-year review of consecutive adult hospital R. Machado-Neves1, J. dos Santos1, D. Carvalho2, R. Araújo2, T. Amaro1
1
autopsies done between January 2007 and December 2018, were divided Pathology Department - Hospital Pedro Hispano, Portugal, 2 Intensive
in three groups. One where the malignant cancer found corresponded to Care and Emergency Department - Hospital Pedro Hispano, Portugal
the patient’s confirmed diagnosed disease; another group with a suspected
diagnosis of cancer through clinical and radiological criteria but without Background & Objectives: Pseudocarcinomatous hyperplasia of the
histologic confirmation; and a final group where there was no clinical lung is a rare, reactive response to an underlying inflammatory or neo-
suspicion of malignant disease. Each group was analysed according to plastic process. It is a benign condition that mimics a malignant neo-
cancer site and histologic characterization. plasm. A correct diagnosis of this entity is important to avoid radical
Results: On a total of 372 autopsies, 67 cases (18.0%), one or more ma- treatment.
lignant neoplasms were found. The average patient age on these cases was Methods: A 83 year-old man, an ex-smoker with ischemic cardiomyop-
68.8 years, with the highest prevalence in males (59.7%). The malignant athy, had an active autonomous life. He was seen in the emergency room
diagnosis that corresponded with the previous histological diagnosis were 9 with dry cough and dyspnea, which was interpreted as a community
(12.7%), the number of clinically suspicion of malignancy without defini- acquired pneumonia and given antibiotics.
tive tissue diagnosis was 24 (33.8%), and the number of patients with He returned with severe respiratory insufficiency and bilateral pulmonary
undiagnosed malignant tumours was 38 (53.5%) of the 71 diagnosis. infiltrates after two weeks and died a week later.
Conclusion: Although the numbers of autopsies performed have de- Results: The lungs (right-1122g; left-944g) had irregular pleura, espe-
ceased in hospitals, this retrospective study shows the importance of the cially over the lower lobes, and compact congested parenchyma.
autopsy as a mean for the medical quality. Even though the recent ad- Histologically, lungs had diffuse alveolar damage (DAD) with hyaline
vances in medical diagnostic, a great number of malignant tumours were membranes formation, fibrin deposition, septal thickening, pneumocyte
found only at the autopsy. hyperplasia, fibroblastic proliferation and intralveolar fibrin plugs. There
Conclusion: Age at diagnosis (> 60 years), higher tumour size, presence was extensive proliferation of metaplastic squamous epithelium with cy-
of LN metastases and absence of oncologic treatment are all negative tological atypia and many mitotic figures. There were some small vessels
factors influencing prognosis, but the only statistically significant with thrombi. Pleura was thickened with fibrosis, muscular hyperplasia
unfavourable independent prognostic parameters in multivariate analyses and osseous metaplasia.
are axillary LN status (p=0.005) and triple negative molecular profile The final diagnosis was acute and organizing diffuse alveolar damage
(p=0.05). Further research is needed to better understand the factors that with extensive atypical squamous metaplasia.
affect this disease and appropriate screening may be warranted. Conclusion: DAD may involve injury and necrosis of bronchiolar
epithelium, which is subsequently replaced by regenerative squa-
mous epithelium spreading from the bronchioles over contiguous
PS-18-005 alveolar septae and producing a bronchiolocentric pattern. The
Dynamics of the number of melanocytes in the hair follicle during metaplastic cells can display an alarming degree of cytologic atypia,
ontogenesis leading to misdiagnosis as carcinoma. Patient’s clinical history, can
M. Kostyaeva1, I. Kastyro1, D. Grosu1, E. Doroginskaya1 provided important clues to the reactive nature of the atypical squa-
1
Peoples' Friendship University of Russia (RUDN University), Russia mous cells.
Virchows Arch

PS-18-009 The cardiac mass observed in the right atrio-ventricular sulcus adipose
Fulminant hepatitis associated with sevoflurane after arthroscopic tissue was infiltration by the same lymphoproliferative lesion observed
lavage of right knee, suspected of septic arthritis. An Authopsy case elsewhere
J. Martinez Martinez1, S. Saez Alvarez2 Hepatic iron overload was observed with severe Kupffer cells
1
Complejo Asistencial Universitario de Leon (CAULE) / CITOCLINIC, hemosiderosis secondary to hemophagocytic process
Spain, 2 Complejo Asistencial Universitario de Leon (CAULE), Spain The lymphatic process is HHV8 +, CD20, CD79a and CD138 negative,
MUM1/IRF4+coexisting with an small amount of EBER+ cells
Background & Objectives: Volatile anesthetics are drugs that are widely Conclusion: The histology of the lymphoproliferative lesion does not
used in surgical interventions. These Halothane-derived drugs present a strictly fits in a single WHO 2017 classification item.
bundle of adverse effects, including drug-induced liver injury (DILI). A full description of our case and review of the literature is presented with
Most recent volatile anesthetics, such as Sevoflurane, show less incidence suggestion that more than separate entities HHV8+ related
of DILI. Sevoflurane-associated DILI is not clearly defined in the bibli- lymphproliferative lesions may be a spectrum sharing in the same patient
ography, without knowing its frequency. There are some case reported, features of separate categories.
which can oscillate from chronic to fulminant hepatitis.
We present a case of fulminant hepatitis associated with sevoflurane di-
agnosed by autopsy study. PS-18-011
Methods: We were requested to perform the autopsy study of a 59-year- Gossypiboma in the abdominal cavity and its clinical implications: an
old patient with a personal history of arterial hypertension and autopsy report
Friedreich's ataxia, who entered via emergency trauma department due J. Melo1, G. Ribeiro Pontes2, H. Moita Mota2, G. Nobre Cavalcanti
to pain and joint inflammation in the right knee, suspected of septic Lucas2, D. Nunes Oliveira1, I. Texeira de Souza3
1
arthritis. Arthroscopic lavage was performed in the operating theatre, Department of Pathology, Postgraduate Program in Public Health,
using sevoflurane, propofol and fentanyle as anesthetics. Subsequently, Faculty of Medicine, University of Fortaleza, Brazil, 2 Faculty of
the patient presented a rapid deterioration in his state of health, showing Medicine, University of Fortaleza, Brazil, 3 Morphofunctional
coma and dying within 3 days despite CPR. Microbiological cultures of Laboratory, Faculty of Medicine, University of Fortaleza, Brazil
blood and synovial fluid were negative. No liver enzyme analytics were
performed. Background & Objectives: The oblivion of surgical compresses during
Results: The autopsy study showed, among other findings, a abdominal operations can lead to serious complications, such as
necroinflammatory lesion of the liver, with perivenular predominance, gossypiboma. To report a case of a patient with gossypiboma.
affecting approximately 70% of the organ parenchyma. This injury was Methods: A 59-year-old woman, previously submitted to appendectomy
characterised by hepatocellular necrosis with ceroid material deposit and and videolaparoscopic cholecystectomy. It evolved postoperatively with
without bilirubin accumulations. No signs of virus infection were ob- flank obstruction. She underwent exploratory laparotomy for lysis of the
served. Bacterial and fungal techniques were negative flanges and adhesions. She sought care two days after hospital discharge
Conclusion: Given the results of the microscopic study, and after with distention and severe abdominal pain, nausea and vomiting. Autopsy
dismissing other causes of hepatic damage, a diagnosis of DILI was was made.
performed. After studying each administered drug, and contemplating Results: At the autopsy, a large amount of purulent fluid and a surgical
chronologic and morphologic characteristic of this case, we considered compress adhered to the intestinal loops were seen in the abdominal
that the liver injury was probably caused by sevoflurane. cavity. Adjacent to this dressing, reddish areas with blackened foci were
We compare with, and review the literature noted. The body was then referred to the Institute that performs medical-
legal autopsies.The oblivion of foreign bodies during abdominal opera-
tions represents a serious complication, estimating an incidence of 1 for
PS-18-010 every 1000-1500 laparotomies and generates inflammatory tissue activity
HHV8+ Lymphoproliferative disease and Kaposi sarcoma in an in its environment which can culminate in septic / exudative or aseptic /
HIV- immunosupressed patient. An autopsy case fibrinous reaction. Most of the time, the diagnosis is only established
J. Martinez Martinez1, S. Saez Alvarez2, F.M. Izquierdo Garcia2 during the operative procedure for intestinal clearing or during the
1
Complejo Asistencial Universitario de Leon (CAULE) / CITOCLINIC, autopsy.
Spain, 2 Complejo Asistencial Universitario de Leon (CAULE), Spain Conclusion: In summary, it was possible to observe that the forget-
ting of foreign bodies during surgeries leads to significant harm to
Background & Objectives: A 83 year old female, followed in our insti- the patients, often culminating in death. However, there are simple
tution for reumathoid artritis treated with immunosupresors was diag- and effective mechanisms to avoid this event, such as adherence to
nosed at 2013 of Kaposi Sarcoma with lessions afecting skin and soft the protocol of safe surgery whose one of the principles is the
palate and followed thereafter. HIV tests were allways negative counting of the surgical material before the patient leaves the oper-
By summer 2017 an axilary lymphadenopathy was biopsied, finding ating room.
reactive-inespecific changes with some HHV8+ cells. Last september,
she was admited with anemia and fever. CT discovered generalized
lymphadenopathy, great splenomegalia with lesser hepatomegalia and a PS-18-012
5 cm cardicac mass. An haemophagocytic síndrome was diagnosed and Maternal mortality by Hellp Syndrome: an autopsy report
related with an active EBV infection. Clinical course was bad and the J. Melo1, J. Barreto Alves Melo2, G. Van Der Linden Fialho2, A. de
patient died. Autopsy was performed Andrade Cavalcante2, M. Albuquerque Montenegro2, M.C. Netherlands
Methods: We were requested for autopsy study, skipping the central Lima2, I. Veras Beleza2, L. Dantas Sampaio Leite2, F.D. Barreto milk2, A.
nervous system Santos Correia2, A.C. Sampaio Braga2, D. Nunes Oliveira1
1
Results: Kaposi Sarcoma was reactivated with skin and colonic mucosa Department of Pathology, Postgraduate Program in Public Health,
lessions Faculty of Medicine, University of Fortaleza, Brazil, 2 Faculty of
Lymph nodes show a distorted microanatomy with effacement of germi- Medicine, University of Fortaleza, Brazil
nal centers, presence of “plasmablastic cells” and other HHV8+ cells
Splenomegaly of 1136 gr was massively affected by a lymphoprolifera- Background & Objectives: HELLP syndrome (HS) is a serious compli-
tive mass with extensive necrosis cation in pregnancy. Report an autopsy of HELLP syndrome.
 Virchows Arch

Methods: Pregnant woman, 27 years old, with loss of colorless fluid of PS-18-014
thin consistency and then thick for 3 weeks and abdominal pain. She Multicentric Castleman disease associated with HHV-8 in a HIV
presented no heart beat upon her admission to the hospital. In the imme- patient
diate postoperative, she evolved with vomiting, headache, tingling in D. Pereira de Melo1, J. Pacheco2,3, E. Fonseca1,4, R. Portugal1
1
lower limbs and profuse bleeding. Laboratory tests: anemia, thrombocy- Centro Hospitalar Universitário de São João, Portugal, 2 Department of
topenia and coagulopathy. She died by hypovolemic shock refractory to Pathology, Centro Hospitalar de São João, Porto, Portugal, 3 Department
vasoactive drugs. of Pathology, Faculty of Medicine of the University of Porto (FMUP),
Results: At the autopsy, focal cerebral, oesophageal and tracheal hemor- Porto, Portugal, 4 Faculdade de Medicina da Universidade do Porto,
rhages, pulmonary congestion and anthracosis, areas of hepatic hemor- Portugal
rhage, cholesterosis, discrete cardiac hypertrophy, focuses of ischemia
and petechiae in the intestine, clear renal corticomedular delimitation Background & Objectives: Castleman disease has three recognized
and petechiae in the pelvic region. Microscopic indicates hepatocellular variants, hyaline-vascular variant, plasmacytic variant and the
necrosis, hepatic steatosis, biliary stasis, chronic cholecystitis and acute multicentric variant associated with HHV-8, the latter can have a fatal
tubular necrosis. We present a case of acute postpartum HS complicated outcome, mostly due to sepsis with multiorganic failure and/or
by disseminated intravascular coagulation that caused rapid maternal lymphoma.
death in the immediate postoperative period after a cesarean section of Methods: We report a case of a 36-year-old man with a 8-year history of
an uncomplicated pregnancy. HIV infection, without treatment in the last 7 years.
Conclusion: HELLP syndrome is associated with severe maternal mor- In January 2018 he was admitted at our Institution due to persistent cough
bidity, especially when it occurs in the postpartum period. Early diagnosis and fever, and began treatment with Clarithromycin. On physical exam-
and an effective therapeutic approach are essential for better prognosis ination multiple cervical and axillary lymph nodes were identified with
and prevention of complications. Further studies are needed to provide a associated splenomegaly. Biopsy of a cervical lymph node revealed
better understanding of its pathophysiology and evolution. Castleman disease associated with HHV-8 with hyalinized
vessels,plasmacytoid, concentrically organized plasmablasts around de-
pleted follicular germ centers.
PS-18-013 Rituximab and HAART were initiated.
Association between haemophagocytic lymphohistiocytosis syn- The symptoms persisted, and the lung disease progressed, with associated
drome with a Kikuchi-Fujimoto linfadenitis with fulminant clinical liver dysfunction. The patient died 3 days later, and an autopsy was
evolution requested.
N. Papaleo1, A. Puche1, M. Gonzalez1, J. Gimeno1, L. Naranjo Hans1, L. Results: Autopsy revealed: icteric skin; enlargement of multiple chains of
Colomo1 and B. Lloveras1 lymph nodes with extensive follicular depletion, with focal HHV-8 pos-
1
Hospital del Mar, Spain itivity; lungs with bilateral and multifocal acute pneumonia; splenomeg-
aly with red pulp congestion; kidney acute tubular necrosis; adrenal
Background & Objectives: 48-year-old female patient from China, pre- necrosis.
senting clinical history of left hemithyroidectomy and Sjögren's syn- Conclusion: Multicentric Castleman's disease associated with HHV-8
drome (SS) causing ocular xerostomia, referred to our Institution due to can progress to a fatal outcome, in this case due to Streptococcus
detection of multiple lymph nodes during a concurrent episode of acute pneumoniae pneumonia and sepsis.
bacterial pyelonephritis. CT revealed multiple and bilateral axillary and Resection of the lymph node is the most effective treatment in limited
iliac lymphadenopathies suggesting an inflammatory, infectious or disease, in multicentric disease CT, antiretroviral therapy and, specially,
tumoural disease. Multiple serological tests as well as axillary lymph Rituximab are the best options for treatment.
node core-biopsy and bone marrow and peripheral blood smears were In the current case, pneumonia progressed with sepsis, and there was no
performed, without achieving a precise diagnosis. As complications, the response to Rituximab or antibiotherapy, leading to the fatal outcome.
patient presented persistent febrile syndrome due to Pneumocystis
jirovecci pneumonia, thrombocytopenia and transaminitis with high bil-
irubin levels. After unfavourable clinical evolution, with progressive re- Wednesday, 11 September 2019, 09:30 - 10:30, Agora 3
spiratory failure, the patient died seven days after the admission PS-19 | Cardiovascular Pathology
Methods: None
Results: Clinical autopsy was performed. Lung parenchyma showed a
diffuse alveolar damage (DAD), consistent with an adult respiratory dis- PS-19-001
tress syndrome. Lymph nodes presented nonprominent follicles with de- Anti-apoptotic role of Galectin-3 at 24-hour post myocardial
pleted cellularity and areas of necrotizing lymphadenitis, containing infarction
karyorrhectic debris and histiocytic cells (with myeloperoxidase and S.N. Al-Salam1, S. Hashmi2
1
TIA-1 positive staining), with a pattern similar to a Kikuchi-Fujimoto College of Medicine & Health Sciences-UAEU, United Arab Emirates,
2
(KF) lymphadenitis. Splenic and bone marrow examination revealed dif- Agha Khan University, Pakistan
fuse hemophagocytosis, with macrophages containing rests of red blood
cells and platelets. Special and immunohistochemical stains performed in Background & Objectives: Galectin 3 (GAL-3) is a beta galactoside
necrotic areas did not detect microorganisms. ‘In situ’ hybridization re- binding lectin that has different roles in normal and pathophysio-
vealed an increased number of lymphoid cells containing Epstein Barr logical conditions. It is up-regulated in animal models of Heart
virus RNA Failure (HF) even before the development of HF. We have inves-
Conclusion: The autopsy shows the coexistence of a KF-type necrotizing tigated left ventricular myocardial changes associated with high
lymphadenitis with histological and clinical findings consistent with an levels of GAL-3 at 24-hour following myocardial infarction (MI)
hemophagocytic lymphohistiocytosis syndrome. This relationship has and before the development of HF symptoms and signs. We have
been previously reported, in patients with some acute viral infections studied if raised GAL-3 has any role in apoptotic mechanisms in
(as a possible trigger), and presenting poor clinical course. This associa- the heart after MI.
tion suggests an eventual alteration of the immune system, especially Methods: Male C57B6/J mice and GAL-3 knockout (KO) mice
considering that these patients usually present autoimmune diseases, such were used for permanent ligation of the left anterior descending
as lupus erythematosus or SS, as in the present case artery of the heart to create infarction in the anterior myocardium.
Virchows Arch

Heart and plasma samples were collected 24 hours after the in- microscopy. Corresponding samples were taken from 16 cadaverous
duction of MI and were used for immunohistochemistry, western cases of children with other diseases (0 to 76 months). The assessed
blot and ELISA. variables included: elastic fiber fragmentation/thinning/disorganisation,
Results: Our results show that there was a significant increase in GAL-3 laminar medial necrosis, mucoid matrix accumulations, smooth muscle
levels in the left ventricle at 24-hour following MI. Our results show that alterations and grade of overall medial degeneration.
proapoptotic proteins like cleaved caspase-3 and cytochrome c were sig- Results: No difference was found between the groups in the individual
nificantly higher in GAL-3 KO mice as compared to GAL-3 wild mice. variables. However, there was a significant difference in the distribution
We also found a significant higher level of BCL2 in GAL-3 wild mice as of the grades of the overall medial degeneration (p=0.016). ToF group
compared to GAL3 KO mice. showed uniform mild degenerative changes, whereas second group
Conclusion: GAL-3 is highly expressed in left ventricular myocardium at harboured spectrum of changes ranging from normal to moderate. The
24-hour following myocardial infarction and mediating antiapoptotic ac- presence and severity of those changes were associated neither with age at
tivities. surgery or mean levels of saturation in ToF group, nor with the age at
death in the second group.
Conclusion: This study emphasizes the histopathological assessment of
PS-19-002 the ascending aorta during the surgical repair of ToF, since the patients
Comparison of the damage to aorta wall in aortitis versus non- demonstrating moderate or severe degenerative changes already in early
inflammatory degenerative aortic diseases childhood may be in increased risk of the subsequent late complications.
K. Amemiya1, E. Mousseaux1, H. Ishibashi-Ueda2, M. Ochiai3, P.
Bruneval1
1
Hopital Europeen Georges Pompidou, France, 2 National Cerebral and PS-19-005
Cardiovascular Center, Osaka, Japan, 3 Department of Cardiology Showa New histopathologic grading system in surgical aortic specimens:
University Northern Yokohama Hospital, Japan three year experience
T. Paavonen1, E. Niinimäki2, A. Mennander3, I. Kholová4
1
Background & Objectives: Frequently aortits is firstly identified by Department of Pathology, Fimlab Laboratories and Department of
histopathological analysis of surgical aorta specimens from aneurysms Medicine and Life Sciences, University of Tampere, Finland,
2
or dissections in the absence of clinical evidence of systemic inflamma- Department of Anesthesiology, Southern Carelian Central Hospital,
tory disease emphasizing the importance of histology for the diagnosis of Lappeenranta, Finland, 3 Department of Cardiothoracic Surgery, Heart
aortitis. Histology can be confusing since medial degenerative changes Hospital, Tampere University Hospital, Tampere, Finland, 4 Department
(MDC) can be prominent in a background where inflammation is limited. of Pathology, Fimlab Laboratories and University of Tampere, Finland
This raises the question of the role of aging or other degenerative process
versus the role of inflammation in the damage to aorta wall. Background & Objectives: Histology for aortic aneurysms and dissec-
Methods: In this retrospective single center study we retrieved 719 as- tions are procured during surgery for these diseases. They are conse-
cending aorta surgical specimens for treatment of aneurysms or dissec- quences of a spectrum of underlying pathologies, syndromes and age-
tions from 2010 until 2018. Aortitis was pathologically diagnosed in 66 related degenerative processes. Several partially overlapping histopatho-
patients (9.2%). MDC [elastic fiber fragmentation and/or loss (EFFL), logical terms have been developed to describe the histopathological
smooth muscle nuclei loss (SMNL), mucoid extracellular matrix accu- changes. A new consensus document was published by Halushka et al
mulation intralamellar or translamellar (MEMA-I or -T, respectively)] (Cardiovasc Pathol 2016) to cover overarching themes: a.unify the no-
was scored according to the consensus statement. Aortitis (n=66) versus menclature of histopathological changes in the noninflammatory degen-
age-matched non-inflammatory degenerative aortic diseases (n=66) were erative aorta; b.provide a new grading scheme to better and more consis-
compared. Aorta diameter was assessed by cardiovascular imaging. tently classify aortic lesions. Gradually we have gathered information on
Results: In 66 aortitis patients; mean age 65 years, 47 patients (71%) the document´s practical applicability in clinical and research context.
were identified pathologically prior to the clinical diagnosis. MDC score Methods: We analysed and scored all aortic samples processed at our
was higher in aortitis than in non-aortitis; EFFL and SMNL scores were pathology department within three years (2016-2018). A total number of
the most severe in aortitis than in non-aortitis (p<0.0001). Moreover 240 samples were scored using both analogue and digital microscopy
higher MDC scores were observed at all aortic size in aortitis versus methods. All samples were scored with the extended version of the scor-
non-aortitis, especially EFFL and SMNL. ing system and tabled as a part of our routine pathology reports.
Conclusion: Aortitis was remarkably associated with severe damage to Results: Overall degeneration score distribution: mild degeneration
the aorta wall resulting in advanced MDC scores. Inflammatory process in 20% cases, moderate degeneration in 53%, and severe degen-
in the aorta wall is responsible for increased MDC over aging. eration in 27% cases. The histopathological scoring results can
with ease be correlated to most important clinical patient records.
Conclusion: Interestingly one fourth of patients were scored as
PS-19-004 severe degeneration, which leads to more careful clinical follow
Histopathological evidence of aortopathy in newborns and infants up. The grading system was quickly learned and adopted by pa-
with Tetralogy of Fallot at the time of surgical repair thologists. The new type of histopathology report was appreciated
O. Fabian1, R. Gebauer1, L. Hornofova1, M. Koblizek1, J. Janousek1 by the clinicians and it ameliorated the communication between
1
Motol University Hospital, Czech Republic clinicians and pathologists. Future prospects include a detailed
analysis in correlation to clinical data.
Background & Objectives: We evaluated microscopic structural abnor-
malities of the ascending aorta in infants with Tetralogy of Fallot (ToF)
and compared them with aortic samples from children that died of other PS-19-006
diseases. We aimed at identification of specific histopathological changes Histopathology of systemic amyloidosis with cardiac involvement
associated with ToF and correlation of their severity with time to surgery M. Rybakova1, V. Baykov1, I. Kuznetsova1, M. Vlasova1
1
and mean levels of saturation in the ToF group, and age at death in the Pavlov First Saint Petersburg State Medical University, Russia
second group.
Methods: The ascending aortic wall samples from 23 children with ToF Background & Objectives: To characterise subtypes and histopatholog-
at the time of surgical reconstruction (2 to 19 months) were evaluated by ical distribution of amyloid deposits in the myocardium
 Virchows Arch

Methods: Heart specimens from 25 autopsies with systemic amy- biopsy is more important than tissue fragment number. Predictive power
loidosis were included in the study. We measured heart weight, of biopsy ITB needs larger numbers to assess it's potential in a clinical
left (LV) and right ventricular (RV) diameter and wall thickness. setting.
For histology H&E and congo red stained slides with subsequent
polarization microscopy were used. Finally, we performed IHC for
P-component, κ-chain, λ-chain, A-amyloid and prealbumin (sub- PS-20-003
stitute for transthyretin). Pathology of intestinal wall and gut microflora translocation in rats
Results: The mean age of patients was 61±3years (nearly equal in during disruption of the mesenteric blood flow and reperfusion
males and females). The average heart weight was 421 g with heart D. Amanova1, M. Tusupbekova1, P. Ivachyov1, S. Kuanyshev1, Y.
chambers dilated in all patients. The thickness of the LV wall was 1.5 Turgunov1
1
cm, RV wall - 0.4 cm. AL-lambda was diagnosed in 80%, AL-kappa Karaganda Medical University, Kazakhstan
– in 5%, mixed type (AL lambda + ATTR) - in 10%, AA - in 5% of
cases. Classical gross presentation (density, fragility, rigidity, in- Background & Objectives: The aim is to study intestinal morphology
creased weight and thickness of the myocardium) were seen only in during gut microflora translocation in different periods of ischemia and
13% of cases. All of them contained AL deposits with intermuscular/ reperfusion in rats.
diffuse and perivascular localization. Nodular forms of heart involve- Methods: 30 male rats were divided into 3 groups: I (n=10) - with ische-
ment were documented in 5% - these were AL cases with focal mia duration 30 min and reperfusion for 60 min, II (n = 10) - with 30 min
perivascular deposits, diffuse involvement of the myocardium was ischemia and 2 hours reperfusion, III (n=10) -sham (only laparotomy and
seen in 82% - these were AL, AA, mixed forms with diffuse peri- follow-up 3 hours). The model of ischemia was performed under general
collagen deposition of amyloid. Microscopically focal deposits ap- anesthesia by clipping superior mesenteric artery, reperfusion was re-
peared as scars with hyaline-like material. stored by removing the clips. The translocation was determined by
Conclusion: The morphological signs of heart involvement in systemic injecting a suspension of fluorescent E.coli and further microbiological
amyloidosis in most patients are non-specific and may be mistaken for examination of organ crops. The morphological study was performed by
coronary heart disease or dilated cardiomyopathy. using of “Leica DM 1000” microscope.
Results: In group I the translocation was detected in 8(80%) of cases,
while morphologically the plethora of vessels was expressed to the max-
Wednesday, 11 September 2019, 09:30 - 10:30, Agora 3 imum, local hemorrhages of the surface mucosal epithelium, weak cellu-
PS-20 | Digestive Diseases Pathology – GI lar infiltration of the submucosa were observed. In 5(62,5%) of cases,
bacteria are found in the mesentery. In group II after 2 hours of reperfu-
sion, translocation was observed in 7(70%) of rats, of which the most
PS-20-001 frequent 5(71,4%) were in the spleen and liver. In this group morpholog-
Preliminary study (in conjunction with KWF Budding Consortium, ically a plethora of capillaries, focal hemorrhages of the submucosa, dif-
Radboud UMC, NL) regarding standardised approach to detection fuse mesentery edema were revealed. In the sham group, the intestinal
of tumour budding in diagnostic cancer biopsies and correlation with and mesentery morphology is intact.
tumour regression grade of post-neoadjuvant resections Conclusion: With an increase in the period of reperfusion, the transloca-
S. Aherne1, D. Gibbons1, D. Winter1, E. Ryan1, B. Creavin1, R. tion of bacteria is more pronounced in the internal organs, the severity of
Kennelly1, S. Martin1, I. Nagtegaal2, K. Sheahan1 morphological changes is maximal after 2 hours of reperfusion.
1
St Vincent's University Hospital, Dublin, Ireland, Ireland, 2 Department
of Pathology, Radboud University Medical Centre, Nijmegen, Supported by Grant of Ministry of Education and Science Republic of
The Netherlands Kazakhstan.
Background & Objectives: Tumour budding (TB) is a histological
biomarker of tumour aggressiveness and an independent prognostic PS-20-004
factor in colorectal cancer (CRC). TB in biopsies may predict poor The spectrum of CKIT and PDGFRA mutations in gastrointestinal
pathological response to radiochemotherapy. We aimed to correlate stromal tumours in Filipino patients
the presence of TB (for biopsies intra-tumoural budding {ITB}) in J.A. Arceño1, A.J. Dumasis1, C.K. Obong1, I.J. Uy1, L.K. Cabral1, J.J.
pre-neoadjuvant therapy rectal cancer biopsies with outcome using Andal1, G.L. Pua1, R. Lo1, R. Li1, D. Ang1
tumour regression grade (TRG) of the corresponding post- 1
St. Luke's Medical Center, Philippines
neoadjuvant resection specimens as a surrogate for survival.
Methods: 106 cases of rectal cancer having both pre-therapy biopsies Background & Objectives: Gastrointestinal stromal tumours (GIST)
containing invasive cancer and post-therapy resection specimens were diagnosis in the Philippines relies purely on immunohistomorphology.
selected from one centre's colorectal cancer database. Each biopsy However, with the advent of molecular testing, the classification, diagno-
contained at least one complete/full face of invasive carcinoma at 200x sis and targeted-therapy for GIST has greatly evolved. The spectrum of
magnification in at least one tissue fragment for inclusion. The biopsies mutations in gastrointestinal stromal tumours is still unknown among
were assessed for ITB on haematoxylin and eosin slides using 20x Filipino patients. This study aims to determine the prevalence of CKIT
objective/per eye piece diameter of 0.785mm2. Assessable field number and PDGFRA mutations in our population diagnosed with GIST.
was also noted. Methods: Fifty eight cases of GIST were retrospectively analysed and
Results: 34 cases (32%) contained ITB. The median ITB for TRG 1 subjected to mutational analysis (Sanger sequencing) for exon 9, 11, 13,
(complete response) was 1.3 and median ITB for TRG2 and TRG3 (par- and 17 of KIT and Exons 12, 14, and 18 of PDGFRA genes.
tial/no response) combined was 0.95. 23% of ITB negative cases had a Results: The mean age of diagnosis is 59 years (29 to 86 years), with
TRG of 1 as opposed to 17% of ITB positive cases. 77% of ITB negative equal gender distribution. The most common tumour site is gastric
cases had partial/no response (TRG2/TRG3) as opposed to 83% of ITB (63.79%), followed by the small intestine (22.41%). Immunoreactivity
positive cases. Median ITB/assessable field was 1; median ITB/case to CD117, DOG1 and CD34 are high at 94.48%, 92.31% and 67.65%,
was1.3. respectively. Majority are diagnosed at larger sizes (>10 cm.); however,
Conclusion: Study demonstrates that ITB is manually assessable on bi- mitotic count remains low (<5 mitosis/50HPF) in most cases. Mutational
opsies (in preparation for digital analysis) and assessable field number/ analysis of the GISTs showed a predominant mutation involving KIT
Virchows Arch

Exon 11 (47.83%) followed by CKIT Exon 9 (13.04%) and PDGFRA Nucleic Acid Amplification (OSNA) is an alternative LN staging
Exon 18 (10.87%). Wild type GIST comprise 47.83% of our cohort. method to the standard H&E. We aimed to evaluate the correla-
Conclusion: This data is important in the management of Filipinos with tion between TB and PDCs with LN total tumour load (TTL),
GIST. The high prevalence of KIT Exon 11 and PDGFRA exon 18 defined as the sum of CK19 mRNA/μL copies present in the
mutation connotes a higher risk of tumours and predicted resistance to LNs of CRC specimens.
targeted therapy, respectively. There is also a need to test for additional Methods: 5931 LNs were freshly isolated from 342 CCR from 3 Spanish
genes to better categorize the wild type GISTs. hospitals. All LNs were analysed with H&E and OSNA. A TTL> 250
copies / μL was considered positive. TB and PDC were evaluated with
H&E and CK19 immunohistochemistry.
PS-20-005 Results: OSNA was positive in 38.3% cases; TB was low (Bd1) in 45%,
Expression of Wingless-related integration site-3A and intermediate (Bd2) in 25% and high (Bd3) in 30% of cases. PDC was low
Olfactomedin4 in pseudopyloric metaplasia of small intestine in pa- grade in 53%, intermediate in 32%, and high in 15% of cases. A positive
tients with Crohn disease correlation was observed between TB and PDC with TTL (r = 0.249, p
M. Antolic1, A. Ognjenovic1, V. Erakovic Haber1, I. Glojnaric1, G. <0.001 for TB, r = 0.266, p <0.001 for PDC), which was higher with
Aralica2,3, M. Banic3, S. Cuzic1 immunohistochemistry evaluation. TB and PDC also correlated with high
1
Fidelta Ltd., Croatia, 2 School of Medicine, University of Zagreb, histological grade, lymphovascular and perineural invasion, pT and pN
Croatia, 3 Clinical Hospital Dubrava, Zagreb, Croatia stages (p <0.001)
Conclusion: In early CRC, molecular LN staging is a promising
Background & Objectives: Crohn disease is a chronic inflammatory approach and an alternative to H&E staining. The correlation be-
disease that can discontinuously affect different parts of the human tween TTL, TB and PDC would imply a more precise LN staging
digestive tract. Most commonly affected are small intestine and compared to H&E and hence for the detection of patients at risk
colon, with pseudopyloric metaplasia as a most prolific feature. of recurrence.
Wnt signalling pathway has an important part in intestinal epithe-
lial stem cell proliferation. The aim of the study was to explore
changes in Wingless-related integration site–3A distribution and PS-20-007
expression of Olfactomedin4 protein, which is a WNT3A target Gene mutation profile in metastatic colorectal cancer of Egyptian
gene and marker for crypt base columnar stem cells. patients
Methods: A study was performed on formalin-fixed paraffin-embedded A. Ayach Salem1, H. Khalil2, E. Anis Ishak1
1
intestinal tissue, obtained by resection either from Crohn patients or car- Kasr El Aini Cairo University, Egypt, 2 Theodor Bilharz Research
cinoma patients (controls). Out of these, three patients had pseudopyloric Institute, Egypt
metaplasia. One micron control and affected small intestine sections were
stained using immunofluorescence (WNT3A antibody, Biorbyt, Background & Objectives: Colorectal cancer is the 4th most common
orb49054) or immunohistochemistry (Anti-OLFM4 antibody, Abcam, cancer and the second cause of mortality worldwide. Recent improve-
ab85046). Stained small intestine tissue samples were scored semiquan- ment in understanding the molecular mechanisms involved in colorectal
titatively according to signal intensity. cancer carcinogenesis allowed the development of targeted therapy and
Results: In the non-IBD small intestine, Wingless-related integra- the selection of the patients that will most benefit from these therapies.
tion site–3A (WNT3A) is secreted by at least two types of intes- The purpose of this study is to investigate the mutation status of different
tinal epithelial secretory cells; Paneth and enteroendocrine cells. driver oncogenes (KRAS/NRAS/BRAF/PIK3CA) and tumour suppres-
In fulminant Crohn disease, elongated crypts showed an increased sor genes (TP53, PTEN) in a cohort of Egyptian patients with metastatic
number of WNT3A positive Paneth cells within crypt stem cell colorectal cancer.
niche and in ectopic position. Olfactomedin4 (OLFM4) labelled Methods: 156 cases of histologically proved metastatic colorectal cancer
enlarged stem cell crypt zone. Most of the cells in pseudopyloric were collected from a private pathology lab during a period of 3 years
gland metaplasia were strongly WNT3A positive, while a small (2015-2018). All cases were submitted to a gene mutation study using the
number of cells were OLFM4 positive. next-generation sequencing-based biomarker study to detect KRAS,
Conclusion: In this study, we have shown that cells of pseudopyloric NRAS, BRAF, EGFR, TP53, PIK3CA and PTEN mutation.
gland metaplasia share some characteristics with intestinal stem cells by Results: Among the 156 cases included in this study, 97 cases (62.179%)
secreting WNT3A and expressing its target protein OLFM4. harbouring gene mutation were detected. TP53 was the most common
mutation detected (61 cases, 41.780%) followed by RAS genes mutation
(60 cases, 38.461%). NRAS and BRAF mutations were significantly less
PS-20-006 common than KRAS mutation. A single mutation was detected in 53
Tumour budding and poorly differentiated clusters in colorectal car- cases (33.974%) with TP53 the most common one detected in 29 cases
cinoma. Correlation with lymph node total tumour load (18.589%). 44 cases (28.205%) showed combined mutations, with
I. Archilla Sanz1, S. Diaz-Mercedes2, I. Gorostiaga3, J.J. Aguirre3, J. {KRAS, TP53} being the most common association.
Guerrero4, N. Castrejon2, J. Tarragona5, J. Camps6, I. Aldecoa1, M. Conclusion: To the best of our knowledge, this is the first study of gene
Cuatrecasas2 mutation profile in metastatic colorectal cancer of Egyptian patients. Our
1
Pathology Department, Hospital Clinic de Barcelona, Spain, results were similar to the data reported in previous studies with TP53 and
2
Pathology Department, Biomedical Diagnostic Center (CDB), RAS gene being the most commonly detected mutations, but the inci-
Hospital Clinic of Barcelona, Spain, Spain, 3 Pathology Department, dences in our study were lower than what was commonly reported.
Hospital Txagorritxu, Vitoria, Spain, 4 Pathology Department, Hospital
Clinic. University of Barcelona, Spain, 5 Pathology Department, Hospital
Arnau de Vilanova, Lleida, Spain, 6 IDIBAPS - Barcelona, Spain PS-20-008
An immunophenotype-based molecular classification of colorectal
Background & Objectives: Tumour budding (TB) and poorly dif- carcinomas
ferentiated clusters (PDC) are related to an aggressive behaviour L. Banias1, I. Jung2, T. Bara3, Z. Fülop3, S. Gurzu1
1
in colorectal carcinoma (CRC). Molecular detection of CK19 University of Medicine, Pharmacy, Sciences and Technology, Targu
mRNA in lymph nodes (LN) of early stage CRC by One Step Mures, Romania, 2 University of Medicine, Pharmacy, Sciences and
 Virchows Arch

Technology, Targu Mures, Romania, 3 University of Medicine, Pharmacy, liver (n = 4), lymph nodes (n = 6) and mesentery (n = 1), in these cases
Sciences and Technology of Tirgu Mures, Romania, Surgery Department, primary origin was found in the bile duct / common bile duct, small
Romania intestine, appendix, pancreas. Other primary sites were lung / bronchus,
cervix, anterior mediastinum, rectum and skin / soft tissues. WHO 2010
Background & Objectives: Colorectal carcinoma (CRC) remains the classification prevalence: NET Grade 1: n=26, Grade 2: n=14, Grade 3:
third most common cancer worldwide, a large number of these patients n=5 and Pulmonary / Bronchial Carcinoid: n=3.
being diagnosed in late stages. Molecular subtyping of CRC may im- Conclusion: We calculate in our Institution an average rate of 1,914 cases
prove the case management and selection of cases for targeted therapy. per 100,000 patients / year.
The aim of the paper was to propose a molecular classification based on
epithelial-mesenchymal transition (EMT) related immunophenotype.
Methods: 84 consecutive CRC cases, without preoperative radio-chemo- PS-20-010
therapy, were included. Based on the EMT-related markers, three molec- Assessment of tumour buds in colorectal cancer. A large-scale inter-
ular subtypes were defined: epithelial (positive for E-cadherin and mem- national digital observer study
brane β-catenin and negative for vimentin), mesenchymal (loss of E- J. Bokhorst1 , H. Dawson 2 , A. Blank2 , A. Lugli 2 , I. Zlobec 2 , L.
cadherin positivity and vimentin positivity or nuclear β-catenin), and Rijstenberg3, M. Vieth4, R. Kirsch5, m. Urbanowicz6, S. Brockmoeller7,
hybrid cases (epithelial core and mesenchymal buds). AE1/AE3 J. Flejou8, J. van der Laak3, F. Ciompi3, I. Nagtegaal3
1
cytokeratin and subcellular expression of Maspin (cytoplasmic versus Radboud University Medical Center, The Netherlands, 2 University of
nuclear) were used for buddings counting, whereas microsatellite status Bern, Switzerland, 3 Radboud University Medical Center,
was evaluated with MLH1, MSH2, PMS2, and MSH6. The Netherlands, 4 University Bayreuth, Germany, 5 University of
Results: There were 31 females and 53 males with ages ranging from 33 Toronto, Canada, 6 EORTC Translational Research Unit, Belgium,
7
to 88 years old. Most of the cases were diagnosed as moderately- Pathology & Data Analytics, Leeds Institute of Medical Research at
differentiated adenocarcinomas (78.57%) in pT3 (70.24%) stage. St. James's, School of Medicine, University of Leeds, United Kingdom,
8
Majority of carcinomas were hybrid-type (48.81%), followed by epithe- APHP Sorbonne Université, France
lial (35.71%) and mesenchymal (15.48%). Maspin nuclear expression
was correlated with the budding-degree (p=0.0328) and was more fre- Background & Objectives: Tumour budding (TB) is a promising and
quently seen in both tumour center (p=0.0385) and buds (p=0.0502), in cost-effective biomarker with strong prognostic value in colorectal can-
hybrid and mesenchymal carcinomas, compared with the epithelial- cer. We previously found moderate agreement between two pathologists
subtype CRCs, which mostly expressed cytoplasmic maspin. scoring TB using the International Tumour Budding Consensus
Conclusion: Nuclear maspin positivity represents an indicator of EMT Conference (ITBCC) guidelines, while considerable discrepancy in iden-
transition of CRC cells. tifying individual tumour buds was observed. To explore this issue fur-
ther, we performed a large-scale international digital observer study on
This work was supported by the University of Medicine, Pharmacy, the assessment of individual tumour buds.
Sciences and Technology of Tîrgu Mureș, Romania, Grant number Methods: We extracted 3000 tumour bud candidates by application
61515/2019. of digital image analysis algorithms. For every candidate, an im-
age patch (size 256x256um) was extracted from pan-cytokeratin-
stained whole-slide images of 36 patients with reported TB.
PS-20-009 Members of a tumour budding consortium were invited to cate-
Neuroendocrine tumours in children and young adults, experiece in gorize each individual object as (1) tumour bud, (2) poorly dif-
the University Hospital Fundación Santa Fe de Bogotá ferentiated cluster, or (3) none of the previous, based on best
R. Lopez1,2, L.E. Barrera-Herrera3 practice and current definitions. Agreement was assessed with
1
Department of Pathology and Laboratories, Hospital Universitario Cohen’s and Fleiss Kappa.
Fundación Santa Fe de Bogotá, Colombia, 2 School of Medicine, Results: Cohen’s and Fleiss Kappa showed a fair to moderate overall
Universidad de los Andes, Bogotá, Colombia, 3 Department of agreement between observers (range 0.24-0.65 and 0.37 respectively)
Pathology and Laboratories, Hospital Universitario Fundación Santa Fe when asked to score 3000 individual objects.
de Bogotá, Colombia Conclusion: Despite adequate agreement between observers in the as-
sessment of TB on patient level, the agreement on individual tumour bud
Background & Objectives: Despite the significant increase in the inci- level using immunohistochemistry is only fair. To better understand the
dence of neuroendocrine neoplasms, they are still considered rare tu- causes of this disagreement, more research is needed involving H&E
mours. In children and young adults its true incidence is not known, most stained images. A machine learning approach may prove especially use-
of the published information correspond to case reports and in Latin ful for a more robust assessment of individual tumour buds.
America there are no data of its true incidence. In the centers of paediatric
oncology, the proportion of these neoplasms is 16%, representing 0.1% of This project has received funding from the Dutch Cancer Society, project
all paediatric tumours. The most frequent location is the cecal appendix number 10602/2016-2.
and is usually associated with acute appendicitis. Extra-appendicular tu-
mours are even more infrequent and course with uncertain malignant
potential, slow growth, high recurence risk and can metastasize even PS-20-011
several years after the initial diagnosis. The use of Stochastic Optical Reconstruction Microscopy (STORM)
Methods: We present a cross-sectional descriptive retrospective study in in formalin fixed paraffin embedded tissue
patients diagnosed with neuroendocrine neoplasms in the Department of S. Brockmoeller1, K. Kouvidi1, H. Slaney1, R. Hughes2, A. Curd2, M.
pathology and laboratories of the University Hospital Fundación Santa Fe Peckham2, P. Quirke1
1
de Bogotá between October 2003 and October 2018, we present the Pathology & Data Analytics, Leeds Institute of Medical Research at St.
demographic, clinical and pathological variables of these patients. James's, School of Medicine, University of Leeds, United Kingdom,
2
Results: In the database of our hospital in a period of 15 years, we found 48 Faculty of Biological Sciences, University of Leeds, United Kingdom
patients (average age, 17.8 years range: 10 - 24); 20 men and 28 women.
60% (n = 29) located in the cecal appendix, 100% with acute appendicitis, Background & Objectives: Colorectal cancer (CRC) with
2 of them with lymph node metastasis. 22.9% were metastatic tumours to amplification/over-expression of cell surface receptors or ligands
Virchows Arch

are specifically targetable (e.g. HER2 and anti HER2 therapy, PS-20-014
EGFr and anti EGFr therapy) but most patients selected for these Clinicopathologic features of radiation-induced enteritis: a
therapies fail to respond due to unknown mechanisms of resis- monocentric surgical study of 41 patients with outcome correlations
tance. Developments in advanced fluorescence microscopy have D. Cazals-Hatem1, J. Didier1, J. Cros2, N. Guedj1, Y. Panis1, F. Joly1
1
made it possible to resolve protein localisation at up to 5nm Hopital Beaujon, France, 2 Beaujon University Hospital / Pathology
resolution. In this pilot study we aimed to develop a robust rou- Department, France
tine methodology for Formalin Fixed Paraffin Embedded tissue
(FFPE) that exploits this technology and explore its potential for Background & Objectives: Surgery is required in patients with symp-
visualisation of ligand-receptor pathways in CRC to increase our toms of radiation-induced enteritis (RE) resistant to medical therapies.
understanding of resistance mechanisms at a cellular level. The study aimed to describe and correlate histopathological features of
Methods: To establish the protocol on FFPE tissue we selected colorectal RE to the initial clinical presentation and to postoperative outcome.
cancer cases with strong HER2 and negative HER2 receptor expression. Methods: All patients with a small bowel resection performed for RE
Previously described cell culture protocols (Creech et al. 2017) were between 2006 and 2017 in our center were studied. Histological data were
modified, optimised and imaged by confocal microscopy using HER2 retrospectively correlated to initial clinical data at radiation and to recur-
(1:250) with affinity purified secondary antibody (1:500). The optimised rence of RE symptoms observed during a median postoperative follow-up
protocol was used in 3D dSTORM on FFPE. of 32 months (occlusion, need for reoperation, prolonged parenteral
Results: Protocols for HER2, EGFR, RAB5 and RAB11 expression on nutrition).
FFPE samples were determined using the confocal microscope. In 3D Results: Forty-one patients were studied (39F/2M), median age 62yo at
dSTORM, high levels of HER2 were localised to aggregates in the membrane time of radiation for pelvic cancer (80% gynaecological). Median time to
and lower levels in the cytoplasm. Further work will focus on imaging and surgery for RE after radiation was 3 years [1-41]. Ileocaecal resections
quantification of further components of the MAPK/ERK pathway in 3D (80% of patients) removed a median small bowel length of 60 cm [10-
dSTORM and imaging multiple proteins in combination to assess ligand- 220]. Histologically, diffuse obliterative arteriopathy was present in 24
receptor and receptor-adapter interactions as well as receptor cycling. (59%) patients, significantly associated to amyotrophy, villous atrophy
Conclusion: STORM microscopy opens up subcellular microscopy in and ulceration observed in 66, 63 and 34% of patients respectively. The
FFPE to Histopathologists. 17 (41%) patients left presented all with serosal sclerosis with adhesions
responsible for occlusion. Arteriopathy was uncorrelated with age and
Supported by NIHR. vascular risk factors present at time of radiation (active tobacco, diabetes,
hypertension, dyslipidemia, combined chemotherapy). Median time to
surgery after radiation was longer in patients with arteriopathy (13 years
PS-20-013 vs 2.6 years, p=0.0002). During the postoperative follow-up, 50% of
Helicobacter pylori infection: a comparative prospective study of patients had recurrence of RE symptoms, uncorrelated to the radiation-
histochemical stains versus real-time diagnosis with EndoFaster® induced arteriopathy.
test Conclusion: The radiation-induced arteriopathy is observed in RE with
A. Caminoa-Lizarralde1, I. Carretero-Barrio1,2, T. Rodajo-Fernandez1,2, ischemic features and occurs very late after the radiation indicating a slow
E. Romio1,2, E. Sanchez-Rodriguez1,3, E. Vazquez-Sequeiros1,3, C. progressive and long-standing vascular injury. It does not influence the
Perna-Monroy1,2 postoperative outcome. In our series, half of the patients was wounded by
1
Hospital Universitario Ramon y Cajal. IRYCIS., Spain, 2 Department of the surgery.
Pathology, Spain, 3 Department of Gastroenterology, Spain

Background & Objectives: Helicobacter pylori (HP) infection has been PS-20-015
implicated in a number of malignant and non-malignant conditions. The Prognostic perspectives of PD-L1 combined with tumour-infiltrating
confirmatory diagnosis of HP requires an endoscopic biopsy, followed by lymphocytes, Epstein-Barr virus infection, and microsatellite insta-
histopathological examination using haemotoxylin and eosin stain or spe- bility in gastric carcinomas
cial stains such as Diff-Quick (DQ) stain and/or Warthin-Starry (WS) M.S. Chang1, E. Choi2, S. Byeon2, S. Park2
1
stain. EndoFaster® is a novel device able to perform real-time ammonium Seoul National University Boramae Hospital, Seoul National University
and pH measurement in gastric juice, allowing HP diagnosis during College of Medicine, Republic of Korea, 2 Seoul National University
gastro-duodenal endoscopy. This study aimed to validate the accuracy Boramae Hospital, Republic of Korea
of EndoFaster® for real-time HP detection.
Methods: Consecutive patients who underwent upper endoscopy in our Background & Objectives: The prognostic potential of PD-L1 is cur-
centre were prospectively enrolled from July to August 2017. During the rently unclear in gastric carcinomas, although the immune checkpoint
endoscopy procedure, gastric juice was aspirated to perform automatic PD-1/PD-L1 inhibitors have produced promising results in clinical trials.
analysis by EndoFaster®, and HP was considered positive (>67 ppm/ml) The purpose of this study was to define the prognostic implications of
or negative (<57 ppm/ml). Accuracy was measured using histology as PD-L1 and immunomodulatory tumour-infiltrating lymphocytes (TILs),
gold standard, with two histochemistry determinations (DQ and WS and further to provide guidance regarding the selection of patients for
stains). Sensitivity, specificity, positive predictive value (PPV), and neg- whom PD-1/PD-L1 blockade immunotherapy would be advantageous.
ative predictive value (NPV) were calculated for EndoFaster® test and Methods: We explored the prognostic implications of programmed death
DQ stain, using WS as gold standard. ligand 1 (PD-L1) in 514 consecutive surgically-resected gastric carcino-
Results: Overall, 80 patients were enrolled, and 86 aspirated gastric mas. Overall survival and recurrence-free survival were evaluated.
juices were studied. In 19 cases (24%) the histology was normal. In the Immunohistochemistry for PD-L1, CD8, FOXP3, and PD-1, and molec-
remaining cases, varying degrees of inflammation were found. Compared ular grouping by in situ hybridization for Epstein-Barr virus (EBV)-
with pathology and WS, sensitivity, specificity, PPV, and NPV were 73%, encoded small RNAs and multiplex PCR for microsatellite instability
84%, 73% and 84% for EndoFaster® test; and 63%, 100%, 100% and (MSI) markers were performed.
82% for DQ stain, respectively. Results: PD-L1(+) tumour cells and PD-L1(+) immune cells were ob-
Conclusion: Biopsy remains the gold standard test in HP infection. served in 101 patients (20%) and 244 patients (47%), respectively.
However, this new technique is useful in monitoring HP eradication or Tumoural PD-L1(+)/immune cell PD-L1(-)/CD8+/low TILs, and late-
to select patients in whom biopsy could be avoided. stage tumours were associated with unfavourable clinical outcomes in
 Virchows Arch

the entire cohort using a Cox proportional hazards model. Tumoural PD- parameters. We examined our data, looking for trends over time and
L1(+)/FOXP3+/low TILs were associated with worse clinical outcomes in associations between assessment score achieved and methodological
the entire cohort, EBV-positive carcinomas, and MSI-high carcinomas parameters.
through univariate analysis. Tumoural PD-L1(+) alone was an adverse Methods: For each of four MMR proteins (MLH-1, MSH-2, MSH-6,
prognostic factor in the entire cohort and EBV-positive carcinomas. PMS-2), data were collated from the Scheme’s database and analysed in
Conclusion: The prognostic impact of PD-L1 may depend on the tumour respect of performance of primary antibody clones, detection methods
microenvironment. The combination of PD-L1 expression and CD8+ and staining platforms.
TILs may serve as an independent prognostic factor. Tumoural PD- Results: Between 2011-19, 28 assessments were conducted (4,447 sub-
L1(+)/immune cell PD-L1(-)/CD8+/low TILs showing a worse prognosis missions). Median number of laboratories subscribed at each run was 169
may be beneficial for combinatorial therapies of anti-PD-L1/PD-1 and (range: 134 – 228). These comprised laboratories located in 30 different
anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA4) that would countries; UK-based laboratories contributed 44.0% of submissions.
promote effector T cells, thus attack the tumour. The mean pass-rate for each MMR protein on samples provided by UK
NEQAS was, MLH-1: 88.9%; MSH-2: 87.7%; MSH-6: 81.8%; PMS-2:
86.8%.
PS-20-017 Improvement in proportions of submissions obtaining a pass over time
Immunogenic phenotype of EBV-negative mismatch repair profi- was seen in all groups (P<0.05, Cochran–Armitage test for trend).
cient gastric cancer Conclusion: Performance of different primary antibodies against all four
B. Dislich1, N. Blaser1, B. Gloor2, K. Mertz3 and R. Langer1 MMR proteins showed very large variations. Staining platforms supplier
1
Institute of Pathology, University of Bern, Switzerland, 2 Department of was not associated with performance differences.
Visceral Surgery and Medicine, Inselspital University Hospital Bern and
University of Bern, Switzerland, 3 Cantonal Hospital Liestal, Switzerland
PS-20-019
Background & Objectives: EBV-positive and mismatch repair deficient Is there an optimal definition for positive circumferential resection
(MMRd) Gastric Cancers (GC) show higher levels of tumour infiltrating margin in oesophageal cancer?
lymphocytes (TILs) and increased PD-L1 expression and thus are more C. Dufour1, B. Brac1, H. Behal1, M. Messier2, E. Leteurtre3,4, C.
likely to respond to immunotherapy. The majority of GC, however, are Mariette3,4, G. Piessen3,4, F. Renaud3
1
EBV-negative and MMR proficient (MMRp). We systematically CHU Lille, France, 2 CHU, Inserm UMRS 1172, Lille, France, 3 CHU,
analysed PD-L1 expression and immune infiltrates in EBV-negative Univ. Lille, France, 4 Inserm UMRS 1172, Lille, France
MMRpGC in comparison to EBV-positive and MMRdGC to evaluate
whether additional tumours may harbor an immunogenic phenotype that Background & Objectives: Positive circumferential resection margin
would make them eligible for immunotherapy. (CRM) is a major prognostic factor in resected oesophageal carcinoma.
Methods: A next generation tissue microarray of 401 primary resected The Royal College of Pathologists (RCP) defines a positive CRM (R1) as
GC was analysed by EBER in situ hybridization, MSH1, PMS2, MSH2, the presence of tumour cells within 1 mm of the circumferential margin
MSH6, PD-L1 and CD8 immunohistochemistry. PD-L1 positivity was and the College of American Pathologists (CAP) as the presence of tu-
defined as tumour proportion score >1%. CD8+TILs and their proximity mour cells at the cut margin of resection. The aim of this study was to
to cancer cells were analysed on the HALO™ image analysis platform. evaluate the clinical impact of a positive CRM (R1) according to the RCP
The total number of CD8+TILs and their tumour proximity was dichot- and CAP definitions.
omized using the median as cut-off. Methods: Patients who underwent radical oesophageal resection for ad-
Results: Twelve cases were EBV-positive, 48 cases MMRd and 341 enocarcinoma or squamous cell carcinoma of the oesophagus (pT3 or
cases EBV-negative MMRpGC. EBV-positive and MMRdGC were more pT4) were selected from 2007 to 2016. They were secondarily excluded
often PD-L1-positive (73%, 19%), demonstrated increased numbers of if CRM was macroscopically incomplete (R2) or if longitudinal resection
CD8+ TILs (92%, 81%) and increased proximity of CD8+TILs to tumour margins were positive. CRM was histologically reassessed using an ocu-
cells (83%, 74%) compared to EBV-negative MMRpGC (5%, 43%, 46%, lar micrometer. Overall survival (OS) and disease-free survival (DFS)
p<0.001 each). PD-L1-positive EBV-negative MMRpGC demonstrated were estimated with uni and multivariate analysis.
increased numbers of CD8+TILs with increased proximity to tumour Results: 283 patients were included. CRM was measured as follows:
cells compared to PD-L1-negative tumours (80% vs 42%; 80% vs 45%; CRM=0mm (n=48), CRM within 1 mm (n=123) and CRM>1mm
p<0.01). Further tumour subgroups showed high CD8+TILs or tumour (n=112). R1 resection, according to both definitions was significantly
proximity despite being PD-L1-negative (n=126 and n=134). associated with poor OS (CAP: p<0.001; RCP: p=0.008). Interestingly,
Conclusion: PD-L1 and CD8 immunohistochemistry, supplemented by CRM=0mm was the optimal definition to predict global and locoregional
digital image analysis, may be helpful to identify probable candidates for recurrence.
immunotherapy in EBV-negative MMRpGC. Conclusion: R1 is a poor prognostic factor in resected oesophageal can-
cer according to the CAP and the RCP definitions. However, CAP defi-
nition appears more accurate to predict prognosis and recurrence.
PS-20-018
Mis-match repair protein antibodies and their performance in the
UK National External Quality Assessment Scheme for PS-20-020
Immunocytochemistry and In-Situ Hybridisation (UK NEQAS ICC Gastric signet ring cell carcinoma: a comparative analysis of clinico-
& ISH) pathologic features
A. Dodson1, S. Parry1 B. Efared1, J. Nshizirungu2, N. Hammas2, H. El Fatemi2, L. Chbani2
1 1
UK NEQAS ICC & ISH, United Kingdom Department of Pathology, Hassan II University Hospital, Fez, Morocco,
2
CHU Hassan II de Fès, Morocco
Background & Objectives: UK NEQAS ICC & ISH carries out external
quality assessment of mis-match repair (MMR) immunohistochemistry Background & Objectives: Signet ring cell carcinoma (SRC) is a dis-
(IHC) at quarterly intervals and has done so since 2011. Participating tinct histological type of gastric carcinoma. The aim of our study is to
laboratory’s stained slides are assessed for technical quality; data are investigate differential characteristics between gastric SRC and other non
collected on primary antibodies used and other methodological SRC carcinomas (nSRC).
Virchows Arch

Methods: It was a retrospective study including 166 patients diagnosed Background & Objectives: Loss of function of any of the four MMR
with gastric carcinoma over a period of 4 years (2014-2017), at the de- proteins (MLH1, PMS2, MSH2, MSH6) results in MMR deficiency
partment of pathology of Hassan II university Hospital, Fès, Morocco. (dMMR) and is associated with the hereditary disease Lynch syndrome.
We have performed statistical comparison of clinicopathological features It’s been shown that dMMR patients respond well to immunotherapy,
between patients with SRC and those with nSRC. therefore MMR proteins are important emerging biomarkers.
Results: 111 patients (66.9%) had nSRC and 55 had SRC (33.1%). Agilent is validating Dako Omnis MMR Immunohistochemistry (IHC)
Patients with SRC were younger (mean age of 50.53 versus 59.78, Panel as a predictive diagnostic assay for OPDIVO® treatment. To sup-
P=0.014). SRC tends to be located in the fundus and in the antro- port a Lynch syndrome intended use, Agilent is also developing a novel
pyloric region (P=0.007). Patients with SRC present more often with anti-BRAF V600E antibody.
pT3 tumours (P˂0.001), with lymph node metastasis (P=0.003). Methods: Analytical testing for Dako Omnis MMR IHC Panel and anti-
Perineural invasion was more frequently found in patients with SRC BRAF V600E antibody includes sensitivity, specificity, precision, robust-
(P=0.005). The median overral survival time was 38.8 months. Patients ness, and stability. Testing was performed on human formalin-fixed,
with nSRC live longer than those with SRC (P=0.284). paraffin-embedded (FFPE) colorectal cancer (CRC) tissues using Dako
Conclusion: Signet ring cell carcinoma is a histological subtype of Omnis automated staining solution with EnVision FLEX visualization
gastric carcinoma with characteristic clinicopathologic features system. Biomarker status was evaluated as intact or loss for MMR and
(younger age, lymph node and perineural invasion). The clinical positive or negative for BRAF V600E.
management of patients should take into account these particular Results: Sensitivity testing of 179 commercially procured FFPE speci-
features. mens resulted in a dynamic range of staining intensities for all antibodies.
MMR antibodies showed an expected bimodal distribution. When eval-
uating 60 specimens for biomarker status by multiple observers, inter-
PS-20-022 observer reproducibility agreement was ≥ 93.3 % and intra-observer re-
Expression of FAP-1 in colorectal adenocarcinoma associated producibility agreement was ≥ 99.0 %. Robustness testing produced
fibroblasts staining variation less than 0.5 intensity grade for the eight most critical
C. Ercan 1 , M. Coto-Llerena 2 , V. Kancherla 1 , G. Nicolas 3 , L. parameters. Reagent stability testing using an accelerated model resulted
Terracciano1, S. Piscuoglio1, M. Fani4 in stability of 24 months.
1
Institute of Pathology, University Hospital Basel, Switzerland, Conclusion:
2
Department of Biomedicine, University of Basel, Switzerland, Analytical testing indicates Dako Omnis MMR IHC Panel plus anti-
3
Division of Nuclear Medicine, University Hospital Basel, Switzerland, BRAF V600E antibody is a sensitive, precise, robust, and stable assay
4
Division of Radiopharmaceutical Chemistry, University Hospital Basel, for detecting target proteins in CRC.
Switzerland

Background & Objectives: FAP-1 is expressed on tumour-associated PS-20-024

fibroblasts in the majority of epithelial cancers and has been associated Eosinophil counts in colon biopsies can predict treatment response to
with tumour growth. In this study, we aim to investigate the expression of vedolizumab in Inflammatory Bowel Disease
FAP-1 in colorectal cancers and correlate its expression with clinicopath- R. Gabriëls1, A.R. Bourgonje1, G. Trentadue1, K.N. Faber2, G. Dijkstra1,
ologic features. G. Kats-Ugurlu3
1
Methods: FAP-1 mRNA expression and clinico-pathologic information Department of Gastroenterology and Hepatology, University of
were obtained from 622-CRC patients and 51 non-tumoural tissue from Groningen, University Medical Center Groningen, The Netherlands,
2
The Cancer Genome Atlas dataset. FAP-1 protein expression was evalu- Department of Laboratory Medicine, University of Groningen,
ated in a cohort of 92 CRCs and 19 non-tumoural tissues by immunohis- University Medical Center Groningen, The Netherlands, 3 Department
tochemistry. FAP-1 expression was scored in cytoplasm of stromal cells of Pathology University of Groningen, The Netherlands
based on percentage of positive cells (0=<1%; 1+=1-10%; 2+=11-50%
and 3+=>51%) and intensity (0= none; 1= weak; 2=intermediate; Background & Objectives: Vedolizumab, an antibody against α4β7-
3=strong). Statistical analysis was performed using log-rank test integrin capable of blocking the migration of several immune cells across
(Survival) and X2 or Fisher’s exact tests. endothelium expressing MAdCAM-1, is a second-line biological treat-
Results: FAP-1 mRNA was significantly upregulated in tumours and ment for moderate-to-severe inflammatory bowel disease (IBD). Because
high expression in tumours was significantly associated with poor sur- of moderate response rates to this drug, there is an urgent need for pre-
vival (p<0.005). Results obtained at the mRNA level were further cor- dictive markers to identify patients who would benefit from vedolizumab.
roborated at protein level. FAP-1 expression was detected in stromal cells Our hypothesis is that the number of mucosal eosinophils can predict
in 90% of the tumours but not in the non-tumoural mucosa. Among those therapy response to vedolizumab.
positive, 24% tumours showed a high-intensity stain while 25% and 41% Methods: We analysed inflamed and non-inflamed colon biopsies of IBD
of tumours showed a weak and intermedia intensity stain, respectively. patients before the start of vedolizumab therapy using hematoxylin-eosin
Semiquantitative staining was scores 1+ in 18%, 2+ in 31%, and 3+ in staining. We selected hot spots of eosinophils at low magnification from
41% of the tumours. Low expression of FAP-1, both at mRNA and digitally-scanned slides. Two independent researchers counted manually
protein level, was found to significantly correlate with stage I tumours the number of eosinophils in three high power fields (HPF, 0.24 mm²).
(p<0.005). Results above 60/HPF were grouped together. Clinical response to
Conclusion: Colorectal tumours with high levels of stromal FAP-1 are vedolizumab was defined at 14 weeks of treatment by using HBI and
more likely to have aggressive disease progression and survival. SCCAI scoring methods.
Results: Baseline median eosinophil count in non-inflamed colon
ascendens mucosa (n=24, Crohn’s disease n=10, ulcerative colitis
PS-20-023 n=14) was significantly higher in responders compared to non-
Development of a mismatch repair immunohistochemistry clinical responders (60 ± 12 vs. 25 ± 7,5 eosinophils/HPF, P<0.001, Mann
trial assay and novel BRAF V600E antibody Whitney U test). Patients with >30 eosinophils/HPF achieved clinical
H. Finkelstein1, V. Tennant1, C. Mayhew1, S. Soleimani1, S. Tabuena- response in 83,3% of cases (n=12), whereas only 8,3% of patients with
Frolli1, J. Lee1, T. Haase2, F. Aidt2, E. Oroudjev2 <30 eosinophils responded (n=12). Eosinophil count in inflamed tissue
1
Agilent Technologies, USA, 2 Agilent Technologies, Denmark was excluded because of differences in inflammation severity.
 Virchows Arch

Conclusion: Based on our results, eosinophilic count can be used to number, and LN ratio (LNR) are well-known prognostic factors in colo-
predict response to vedolizumab in IBD patients. Our method should rectal carcinoma.
further be validated in a larger cohort. Methods: The relationship between clinicopathological parameters
and the presence of TDs, number of harvested LNs, N stage, positive
LN number, and LNR was investigated in 278 consecutive patients
PS-20-026 who underwent surgery for colorectal adenocarcinoma.
The influence of the genetic and immunologic context in the develop- Results: Binary logistic regression analysis revealed that mucinous
ment of colorectal adenoma tumour histology and lymphovascular invasion (LVI) were inde-
D. Garcia1, I. Gullo2,3,4, L. Spaans5, S. Miranda6, J. Reis6, J.L. Costa6, F. pendent risk factors for the presence of TD (p=0.014 and
Carneiro7, J.C. Machado8 p=0.001, respectively). Age, tumour localisation, and pT stage
1
Medical Faculty of the University of Porto, Portugal, 2 Department of were statistically significant parameters affecting harvested LN
Pathology, Centro Hospitalar de São João, Porto, Portugal, 3 Department number (p=0.002, p=0.032, and p=0.015, respectively). Only
of Pathology, Faculty of Medicine of the University of Porto (FMUP), LVI was an independent risk factor for LN metastasis (p=0.000),
Portugal, 4 Institute of Molecular Pathology and Immunology at the whereas age, mucinous tumour histology, and LVI were indepen-
University of Porto (Ipatimup), Instituteo de Investigação e Inovação dent risk factors for higher LNR (p=0.003, p=0.001, and p=0.042,
em Saúde (i3S), Portugal, 5 Maastricht University, The Netherlands, respectively). On univariate analysis, only LVI was significantly
6
I3S/Ipatimup, Portugal, 7 I3S/Ipatimup; Centro Hospitalar de São correlated with a positive LN number ≥ 5 (p=0.016).
João; FMUP, Portugal, 8 Institute of Molecular Pathology and Conclusion: Mucinous tumour histology and LVIwere independent
Immunology of the University of Porto (Ipatimup), Portugal predictive factors for the presence of TDs and higher LNR. Also
older age influenced LNR. Younger age, right tumour location
Background & Objectives: Overcoming immunosurveillance is a and advanced pT stage increased independently the number of
major step in the progression of many types of tumours. Several harvested LNs. These results have to be proven in larger cohorts.
immune escape strategies have been identified, including
immunoediting and the establishment of an immune suppressive mi-
croenvironment. The aim of the present study was to determine PS-20-028
whether the hereditary or sporadic context has any influence in the Plasmacytoid carcinomas of the stomach: the immunoprofile high-
relationship between immune surveillance and tumour development, lights the potential targeted therapy of these rare histological
using sporadic and familial adenomatous polyposis (FAP) related variants
colorectal adenomas as a model. S. Gurzu1, C. Molnar2,3, L. Banias1, M. Sincu3, Z. Kovacs4, I. Jung4
1
Methods: The immune tumour-infiltrating cells of a total of 58 low-grade University of Medicine, Pharmacy, Sciences and Technology, Targu
and 18 high-grade colorectal adenomas were examined and compared, Mures, Romania, 2 University of Medicine, Pharmacy, Sciences and
using immunostaining for CD3, CD4, CD8, CD57, CD68 and FoxP3. Technology, Targu-Mures, Romania, 3 Clinical County Emergency
The mutational burden was evaluated by Next Generation Sequencing Hospital, Targu Mures, Romania, 4 University of Medicine, Pharmacy,
and was compared between sporadic and FAP adenomas. Sciences and Technology, Targu Mures, Romania
Results: FoxP3 and CD68 counts were significantly higher in sporadic
low-grade dysplasia (p=0.0003 and p=0.0103, respectively), and FoxP3 Background & Objectives: Plasmacytoid carcinoma is known as a
and CD4 counts were found to be significantly higher in high-grade rare and aggressive tumour of the urinary bladder. Its occurrence in
sporadic dysplasia (p=0.0008 and p=0.0018, respectively) when com- the gastrointestinal tract is extremely rare and the proper therapeutic
pared with corresponding lesions in FAP patients. The mutational burden management is still unknown. The aim of the paper was to reveal the
was found to be significantly higher in FAP samples (p=0.0040), when immunoprofile of these rare tumours. Besides the markers used for
compared with sporadic samples. differential diagnosis, we aimed to emphasize the microsatellite sta-
Conclusion: This study suggests that the immune microenvironment of tus, epithelial mesenchymal transition (EMT), and angiogenic
sporadic and hereditary lesions is different. Sporadic lesions contain a immunophenotype. Predictive biomarkers such HER-2, c-Kit, and
higher number of immune suppressive Treg cells and a lower mutational c-MET were also used.
burden, hinting at a stronger immune selective pressure. In contrast, he- Methods: In order to elucidate the molecular background of these rare
reditary lesions seem to benefit from a more tolerant immune microenvi- tumours, we performed a complex molecular examination and checked
ronment, allowing for the development of lesions with a higher mutation- the immunoprofile of five gastric plasmacytoid carcinomas (surgical
al burden and lower immune cell infiltration. specimens, primary tumours of the stomach) diagnosed by our team in
the last three years. The possibility of metastatic tumours were excluded.
D. Garcia and I. Gullo are first authors in equal proportions. A panel of 39 diagnostic and predictive biomarkers have been used.
Results: All of the patients, aged between 67 and 83 years, died below
6 months after surgery. The diagnosis was based on double positivity
PS-20-027 for AE1/AE3 Keratin and CD138. The tumour cells proved to be
Assessment of colorectal resection specimens for the predictor fea- negative for VEGF-A, S100, HER-2, c-KIT, etc. All of the cases
tures of presence of tumour deposits and lymph node characteristics: showed a microsatellite stable (MSS) status and presented EMT fea-
importance of mucinous tumour histology tures: E-cadherin negative, SLUG positivity, β-catenin nuclear posi-
G. Kir1, R.B. Girgin1, T. Soylemez1, S. Gundogdu2, I. Tosun3, A. tivity and focal positivity for vimentin. The c-MET diffuse positivity
Gapbarov4, G. Bas4, O. Alimoglu4 was also emphasized.
1
Istanbul Medeniyet University, Department of Pathology, Turkey, Conclusion: Patients with gastric plasmacytoid carcinoma can benefit by
2
Istanbul Medeniyet University, School of Medicine, Turkey, a targeted therapy based on anti-c-MET drugs but their molecular profile
3
Umraniye Training and Research Hospital, Department of suggest lack of response to antiangiogenic (anti-VEGF), anti-HER-2
Pathology, Turkey, 4 Istanbul Medeniyet University, Department drugs or immunotherapy. The agressivity seems to be induced by the
of General Surgery, Turkey EMT of tumour cells.

Background & Objectives:The presence of tumour deposits (TDs), This work was supported by Romanian National Authority for Scientific
number of harvested lymph nodes (LNs), LN positivity, positive LN Research, CNCS–UEFISCDI, grant number 20 PCCF/2018.
Virchows Arch

PS-20-029 Background & Objectives: About 50% of gastric cancer (GC) has focal
Tumour budding in 3D: a novel approach to visualisation and neuroendocrine differentiation. The neuroendocrine cells in GC could be
characterisation predictive for patient’s survival and treatment.
T. Haddad1, N. Farahani2, D. Treanor3, M. Hale3, F. Doubrava-Simmer4, Human gastric mucosa contains chromogranun A (CHA) endocrine cells
J. Bokhorst1, M. Goodman5, J. van der Laak4, I. Nagtegaal6 (ECs) distributed mainly in gastric body and very small number in the
1
Radboud University Medical Center, The Netherlands, 2 3Scan, USA, antrum. Serotonin (SER)+ECs are less far numerous thought stomach.
3
University of Leeds, United Kingdom, 4 Radboud University Medical Somatostatin (SOM)+ECs are located mainly in gastric body
Center, The Netherlands, 5 3Scan, USA, 6 Department of Pathology, intermingled with ghrelin (GHR)+ECs. The gastrin (GAS)+cells are lo-
Radboud University Medical Centre, Nijmegen, The Netherlands cated mainly in gastric antrum. Presence of GHR+ECs in GC is docu-
mented by Tian and Fan, 2012 and it is stimulating the proliferation of GC
Background & Objectives: Scoring tumour budding at the invasive front cells.
of a colorectal carcinoma is primarily performed on slides using two- The aim of the study is to determine EC presence in GC tissue and in the
dimensional diagnostic visualization. This limits our understanding of this overlying mucosa, and their prognostic value for the patients.
powerful and independent prognostic biomarker. To better understand the Methods: Surgical biopsy specimens from 95 GC patients (n=56 males,
invasive front, we set out to explore the infiltrative margin in three- n=39 females) are investigated immunohistochemically with anti-CHA,
dimensions by deploying three distinct visualization modalities to quantita- anti-SOM, anti-GAS, anti-SER and anti-GHR antibodies.
tively assess their feasibility and efficacy in characterizing tumour budding. Immunofluorescence co-localization studies are done using anti-GHR,
Methods: Immunofluorescence Confocal Microscopy: Thick sections anti-SER, anti-SOM and anti-CHA antibodies in order to assess co-
(up to 90 microns) of formalin-fixed paraffin-embedded (FFPE) colorec- expression of SER and SOM with GHR.
tal carcinoma tissue were stained using a free-floating immunostaining Results: GC patients in stage I-II are 27 and in stage III-IV are 68. GCs
protocol and imaged via confocal microscopy. contains mainly SOM+ECs and about twice lower values of GAS, CHA,
Knife-Edge Scanning Microscopy: Technology developed by SER and GHR. The overlying mucosa shows increased EC number and
3Scan involves high-precision serial slicing (5 micron) and simul- microendocrine cell nests mainly with CHA and GAS.
taneous scanning of a whole-mount H&E stained FFPE colorectal Survival analysis show that increased numbers of GAS+ECs and of
carcinoma tissue block. SER+ECs in tumour tissue are associated with longer survival
3D Digital Pathology: Serially sliced (4 micron) FFPE colorectal carci- Conclusion: The presence of ECs in tumour tissue of GC is related to
noma tissue blocks are mounted on glass, scanned and registered to create patient’s prognosis.
a virtual 3D reconstruction.
Results: This work was financially supported by the National Science Fund,
Bulgaria, Research grant number KП-06-H23/2 from 17.12.2018.

Technique Advantages Disadvantages

PS-20-031
Immunofluorescence -Single-cell imaging -Time-intensive Epithelial budding: a promising morphological biomarker in colo-
Confocal Microscopy -Multiplexed staining -Limited tissue thickness rectal adenomas?
-Antibody specific complications A. Handra-Luca1, E. Papagianni2, C. Magkou2
1
Knife-Edge Scanning -Converts entire block into -Consumes tissue APHP University Paris Nord, France, 2 Evangelismos Hospital Athens,
Microscopy high quality, serially sliced -Near single cell resolution Greece
and registered data
-Provides complete visualization Background & Objectives: Endodermal budding is considered a
of entire tissue basic process which leads to primitive tube development (gastru-
3D Digital Pathology -High quality, single-cell -Involves manual work-up lation). Epithelial budding and ramification of primitive tubes re-
resolution data of tissue slicing, staining, sult in tubular branching in colorectal adenomas (CRA). Beta-
-Similar to diagnostic whole and scanning catenin is more frequent in epithelial budding zones of CRA
slide images -Limited thickness due to (Kirchner and Brabletz, 2000).
-Preserves tissue technician's capabilities We aimed to study the relationships of epithelial budding to baseline
for exact serial slicing morphological features of CRA, to the stem phenotype protein CD133
and to PTEN.
Methods: Baseline morphological features were assessed for a series of
Conclusion: Each platform for 3D visualization displays a unique per- colorectal adenomas (n=127). These results were analysed with regard to
spective with clearly defined advantages and disadvantages at visualizing presence of epithelial budding and to immunohistochemical expression of
the invasive margin of a colorectal carcinoma. When used synchronously, CD133 and PTEN (as evaluated on tissue microarrays constructed from
these methods provide an un-paralleled view with novel insights into the the adenoma tissues).
morphological, molecular and micro-environmental features of tumour Results: Epithelial budding (81%) correlated to extent of the epithelial
budding, thereby furthering our understanding of tumour heterogeneity adenomatous component (as compared to stromal component), adenoma
and cancer invasion. size, presence of high grade dysplasia, left colon location, as well as to
presence of glandular kysts (defined as a 3-fold increase in glandular
Supported by Dutch Cancer Society. lumina) (p<0.05 for all comparisons). Presence of glandular cysts was a
significant predictor of epithelial budding (logistic regression model,
p=0.01). Epithelial budding correlated to lack of cytoplasmic CD133
PS-20-030 and to cytoplasmic PTEN (p<0.05 for both comparisons).
Gastric cancer with neuroendocrine differentiation and tumour Conclusion: In conclusion, epithelial budding in colorectal adenomas,
development predicted by presence of glandular cysts, correlated to large adenoma size,
M. Hadzhi1, K. Dinkova2, J. Ananiev2, M. Gulubova2 to left colon location as well as to high grade dysplasia.
1
Medical Faculty, Trakia University, Bulgaria, 2 Department of General
and Clinical Pathology, Medical Faculty, Trakia University, Bulgaria This wok was supported by the SNFGE.
 Virchows Arch

PS-20-032 cells correlated positively with CD1a+ DCs in the invasive front (IF)
The expression profile of EPHB3 during colorectal cancer progres- (Rho=0.262, p=0.008); with CD123+ DCs in the tumour stroma (TS)
sion and the prognostic impact of EPHB3 in colorectal cancer (Rho= 0.275, p=0.013); and with CD83+ DCs in TS (Rho=0.269,
patients p=0.006).
S. Song1, C. Hyun2 Conclusion: In conclusion we may state that IL-6 released from
1
School of Medicine, Jeju National University, Republic of Korea, immune cells (macrophages or T lymphocytes) in TME modulate
2
Department of Pathology, Jeju National University Hospital, Republic DC-induced T cell polarization in direction of Th17 and Th22 cell
of Korea development. MSS patients show increased number of immuno-
suppressive factors in TME such as IL-6, STAT3 and IL-17. The
Background & Objectives: Ephrin type-B receptor 3 (EPHB3) is a protein early stages of CRC show increased numbers of as IL-6, STAT3
that in humans is encoded by the EPHB3 gene. The Eph family of receptors and IL-17 that maintain immunosuppressive TME promoting can-
are divided into two groups based on the similarity of their extracellular cer development.
domain sequences and their affinities for binding ephrin-A and ephrin-B
ligands. Ephrin receptors make up the largest subgroup of the receptor This work was financially supported by the National Science Fund,
tyrosine kinase (RTK) family. We aimed to investigate the expression profile Bulgaria, Research grant number KП-06-H23/2 from 17.12.2018.
of EPHB3 during colorectal cancer (CRC) progression and determine the
prognostic impact of EPHB3 in a large cohort of CRC samples.
Methods: We examined EPHB3 expression in 610 Formalin-fixed PS-20-035
Paraffin-embedded colorectal cancer tissue specimens using immunohis- Development of immunohistochemistry based molecular classifica-
tochemistry. The relationships between EphB3 expression and clinico- tion of colorectal carcinomas; correlation between transcriptome
pathological parameters, KRAS mutations, BRAF mutation, MSI and sur- analysis and immunohistochemical study
vival were evaluated using Spearman’s rank correlation and Kaplan– M. Jang1
1
Meier survival analyses, respectively Department of Pathology, Yonsei University College of Medicine,
Results: EPHB3 expression was higher in CRCs than in normal mucosa Seoul, Republic of Korea
and was associated with intestinal stem cell markers (EPHB2, OLFM4,
LRIG1) and CD44, a candidate cancer stem cell marker. EPHB3 positiv- Background & Objectives: Colorectal cancer (CRC) is the third most
ity was observed in 24% of 610 CRCs and showed negative correlations common cancer worldwide, with a 5-year overall survival of 65%. There
with differentiation, lympho-vascular invasions and TNM stages. is an urgent need to establish the classification strategy to identify the
Enhanced EPHB3 expression significantly declined during the patient group who may benefit from adjuvant therapy. Several studies on
adenoma-carcinoma transition and invasion into deeper layers. In partic- molecular heterogeneity in CRCs have used gene expression-based data
ular, a substantial reduction of EPHB3 was observed in the budding to assess disease stratification. However the practical approach to classify
cancer cells at the invasive fronts. Notably, EPHB3 was positively asso- the molecular subtype is in need. This study aimed to investigate and
ciated with microsatellite instability phenotype but was not associated establish algorithms for immunohistochemical assessment of molecular
with CpG island methylator phenotype, KRAS and BRAF mutations. subtypes.
Conclusion: EPHB3 positivity was a prognostic marker for better clinical Methods: The gene expression data of training cohort of a total 101
outcomes in CRC patients. Taken together, our data suggest the suppres- CRCs were used to classify into the consensus molecular subtypes
sive role of EPHB3 in the late stage of CRC progression. (CMSs). We selected thirteen markers available for IHC that
overexpressed >1.5 folds in one subtype to that of the other 3 subtype,
and included another 19 previously proposed as molecular markers. We
PS-20-033 finally constructed IHC classifier using 9 factors. The validation cohort
IL-6/STAT3 immune cell interactions in the immunosuppressive tu- (n=416) was classified into CMSs using the IHC classifier and the clin-
mour microinvironment of CRC icopathologic characteristics were evaluated.
K. Ivanova1, D. Chonov2, K. Dinkova1, M.M. Ignatova3, T. Vlaykova4, Results: Using SNAI1, MUC2, SPINK4, KIT, CDX2, ZMYND8, TFF3,
M. Gulubova1 MUC5AC, and MSI status by MMR markers, IHC classifier was con-
1
Trakia University, Medical Faculty, Department of General and Clinical structed (the accuracy: 0.825, 95% CI=0.737-0.825, AIC: 134.771, 95%
Pathology, Bulgaria, 2 Medical Faculty, Trakia University, Department of CI = 134.507-160.549). Application to validation cohort (n = 416) re-
Surgery, Bulgaria, 3 Trakia University, Medical Faculty, Bulgaria, vealed that similar subtype specific characteristics with training cohort
4
Medical Faculty, Trakia University, Department of Chemistry and and poor prognosis of CMS4. Using the IHC classifier, we found that
Biochemistry, Bulgaria CMS3 and CMS4 are bad prognostic group from FOLFOX
chemotherapy
Background & Objectives: IL-6/STAT3 induces and maintains mainly Conclusion: This study proposes the practical IHC classifier predicting
pro-tumour microenvironment (TME) and IL-6 trans-signalling is ob- the prognosis of CRCs.
served in inflammatory cells. IL-6 inhibits dendritic cell (DC) maturation
and induces generation of Th17 cells.
The aim of the present study is to enumerate IL-6+ and STAT3+ immune PS-20-036
cells, Treg and Th17 cells in colorectal cancer (CRC) and to find an Isolated tumour cells in regional lymph nodes of patients with ade-
association with microsatellite instability/stability (MSI/MSS) status and nocarcinoma of the ooesophagogastric junction representing part of
with DCs. a true metastasis
Methods: Surgical biopsy specimens from 104 patients (n=53 males, D.N.M. Jepsen1 , A.K. Fiehn 1, M.P. Achiam 2 , H. Ugleholdt 1 , B.
n=51 females) are MSI tested and the immune cells positive for IL-6, Federspiel3
1
STAT3, IL-17, FoxP3 and for DCs (CD1a, CD83, CD11c and CD123) Department of Pathology, Rigshospitalet, Denmark, 2 Department of
are immunostained. Non-parametric analysis (Mann-Whitney) is used. Surgical Gastroenterology, Rigshospitalet, Denmark, 3 Department of
Results: IL-6+, STAT3+ and IL-17+ immune cells are more in number in Pathology Copenhagen University Hospital Rigshospitalet, Denmark
MSS patients as compared to MSI patients. Only FoxP3+ cells are less in
number in MSS patients. All investigated immune cells are more in num- Background & Objectives: Regional lymph node metastases in patients
ber in stages I+II CRC as compared to stages III+IV CRC. IL-6+ immune with carcinoma of the oesophagogastric junction (EGJ) is an important
Virchows Arch

1
prognostic factor. The impact of lymph nodes with isolated tumour cells Department of Pathology, "Victor Babeș" University of Medicine and
(ITCs) is not completely clarified. The aim of this study was to determine Pharmacy, Timișoara, Romania, 2 Department of Pathology, Emergency
the prevalence of regional lymph nodes with ITCs and to examine how County Hospital Timișoara, Romania, 3 Surgery Department II, "Victor
often ITCs in fact represent part of a true metastasis. Babeș" University of Medicine and Pharmacy, Timișoara, Romania,
4
Methods: The study included surgical specimens of 126 patients with ade- Surgery Department II, Emergency County Hospital Timișoara,
nocarcinoma of the EGJ. Lymph nodes with ITCs were identified. Romania
Supplementary sections were performed and stained with HE and cytokeratin.
All slides were evaluated for the presence of tumour cells and it was deter- Background & Objectives: The therapeutic management for colo-
mined whether the criteria for a metastasis was met on the additional sections. rectal cancer (CRC) depends on various factors. The aim of this
Results: ITCs were detected in 59 (1.7%) of 3454 lymph nodes and in 41 study was to identify the possible parameters which correlate with
(32.5%) of 126 patients. In 29 (49.2%) lymph nodes with ITCs on the lymph node metastasis (LNM) and distant metastasis (M) in CRC
primary slide further sections resulted in a changed status from ITC to a patients.
metastasis. In 7 (5.6%) of the 126 patients the pN category was changed. Methods: We performed a retrospective study on a group of 150 patients
Conclusion: In patients with adenocarcinoma of the EGJ the presence of diagnosed with CRC at the Emergency County Hospital “Pius Brinzeu”
ITCs in regional lymph nodes is a common observation. ITCs often repre- from Timisoara, Romania. The study group comprises three subgroups of
sent a real metastasis. To obtain a correct pN category we strongly recom- 50 patients each (local, nodal and distant disease). Associations between
mend thorough examination with additional levels when ITCs are observed. the clinicopathological variables including gender, age, tumour location,
mucinous differentiation, tumour grade (G), depth of tumour invasion
(pT), lymphovascular invasion (LVI) with the three CRC patients’ sub-
PS-20-037 groups were analysed using the Chi-square and Fischer exact test.
The prognostic significance of tumour budding and poorly differen- Results: The CRC cases with evidence of LVI had a significantly higher
tiated clusters in colorectal carcinomas risk of nodal and distant disease than those without LVI. In multivariate
A. Jurescu1, A. Gheju1, A. Văduva1, I. Mihai1, O. Vița1, R. Cornea1,2, M. analysis the rectal location (p = 0.0430), low differentiation (G3-G4, p =
Cornianu1,2, F. Lazăr3,4, S. Tăban1,2, A. Dema1,2 0.0013), depth of invasion (pT3-T4, 0.0443), and LVI (p < 0,0001) were
1
Department of Pathology, "Victor Babeș" University of Medicine and significantly related to tumour spread, while the independent risk factor
Pharmacy, Timișoara, Romania, 2 Department of Pathology, Emergency for distant metastasis was LVI (p < 0,0001) only.
County Hospital Timișoara, Romania, 3 Surgery Department II, "Victor Conclusion: In our study, several risk factors correlate highly with
Babeş" University of Medicine and Pharmacy, Timișoara, Romania, nodal disease, while for the distant disease only the LVI plays an
4
Surgery Department II, Emergency County Hospital Timișoara, important role. The potentials prognostic factors for CRC patients
Romania must be well known and all the important parameters for the
therapeutic management must be standardised and included in
Background & Objectives: The aim of our study was to assess the tumour the pathological report.
budding (TB) and the poorly differentiated clusters (PDCs), as additional
grading tools in the evaluation of colorectal carcinomas (CRC). According
to the International Tumour Budding Consensus Conference (ITBCC) from PS-20-039
2016, based on the presence of budding differentiation (BD), the TB grading Combined positive score measured by pathologists and digital image
system comprises BD1- low budding, BD2- intermediate budding, and analyses are not significantly different in predicting responses for
BD3- high budding. The PDCs-grading system (PDCs-G), as proposed by immune checkpoint blockade therapy in gastric cancer patients
Ueno et al, includes PDCs-G1, PDCs-G2, and PDCs-G3. H. Kim1, H. Jung2, Y. Jang1, S.T. Kim3, J. Lee3, W.K. Kang3, K. Kim2
1
Methods: We performed a retrospective study on a group of 21 CRC Department of Pathology and Translational Genomics, Samsung
patients that underwent robotic surgery between 07/2015-07/2016, at the Medical Center, Republic of Korea, 2 Department of Pathology and
Emergency County Hospital “Pius Brinzeu” from Timisoara, Romania. Translational Genomics, Samsung Medical Center, Sungkyunkwan
The CRC cases were classified, on H&E scanned slides, using the TB University School of Medicine, Seoul, Korea, 3 Division of
grading system and the PDCs-G. We analysed the associations between Haematology-Oncology, Department of Medicine, Samsung Medical
TB/PDCs grades with other factors: gender, the location of the tumour, the Center, Sungkyunkwan University School of Medicine, Seoul, Republic
degree of differentiation, depth of invasion (pT), tumour border configura- of Korea
tion, lymphovascular invasion (LVI) and lymph node metastases (LNM).
Results: Using TB grading system, 9% of the cases were BD1, 24% BD2 Background & Objectives: Programmed death ligand-1(PD-L1) im-
and 67% BD3, while in the PDCs-G, 14% cases were PDCs-G1, 48% PDCs- mune checkpoint blockade is one of emerging methods for cancer immu-
G2 and 38% PDCs-G3. In multivariate analysis, BD3 was significantly as- notherapy. PD-L1 immunohistochemistry is used to predict likelihood of
sociated with rectal location (71.43% cases), pT3-4 (64.29%) and with infil- response to anti-PD-1 or anti-PD-L1 therapy. However, intra- and inter-
trative and mixed tumour border configuration (92.86%, p = 0.0251). observer variability influence the results of PD-L1 expression. Unlike
Moreover, PDCs-G3 presented significant correlation with pT3-4 (87.50%), non–small cell lung cancer using PD‐L1 expression determined by tu-
LNM (62.50%) and especially with LVI (62.50%, p= 0.0139). mour proportion score, gastric cancer uses combined positive score. We
Conclusion: High TB and PDCs grades correlate with other negative aimed to compare the results of digital image analysis and interpretation
prognostic parameters in CRC cases. These new parameters/methods of by pathologists predicting responses for pembrolizumab in gastric cancer
classifications could be helpful for risk stratification and seem to present patients.
prognostic significance for CRC patients. Methods: Either primary or metastatic gastric cancer tissue consisting of
biopsy (22) and resected specimens (17) from 2013 to 2017, and enrolled
for pembrolizumab clinical trial at Samsung Medical Center were
PS-20-038 reviewed. Among them, 39 cases were finally selected based on the
Clinicopathological features of primary colorectal carcinomas corre- availability of tissues and clinical responses for pembrolizumab. The
lated with lymph node and distant metastases PD-L1 22C3 PharmDx (Dako) immunohistochemistry slides were
A. Jurescu1, A. Gheju1, S. Tăban1,2, M. Cornianu1,2, A. Mureșan1,2, C. interpreted by digital image analysis software and two pathologists for
Lăzureanu1,2, R. Cornea1,2, E.G. Olteanu1, V. Lupu1, C. Duță3,4, A. PD-L1 combined positive score, and the results were compared to the
Dema1,2 clinical responses for pembrolizumab.
 Virchows Arch

Results: With the combined positive score cutoff of 1 for Methods: The activity of β-catenin in CRC cells were activated/inhibited
pembrolizumab approval, 33 (84.6%) out of 39 cases showed con- by small molecule compounds GSK-3 inhibitor BIO and tankyrase inhib-
cordant results by digital image analysis and pathologists’ interpre- itor XAV939. The downstream target genes of WNT/β-catenin signalling
tation. In 6 (15.4%) cases, discordant results were caused by weak pathway were screened by cDNA microarray. Apoptosis induced by 5-
staining of PD-L1 (n=2), anthracotic pigments deposition (n=1), Fu, cell cycle distribution and expression levels of β-catenin/TCF12/
decalcification artifacts (n=1), and unknown reasons (n=2). In sta- Caveolin-1 and multidrug resistance proteins (MRPs) were elucidated
tistical analyses, PD-L1 combined positive score measured by pa- after β-catenin activation/inhibition and Caveolin-1 overexpression/inter-
thologists and digital image analysis did not show significant dif- ference. The effect of XAV939 on proliferation and apoptosis induced by
ference in predicting responses for pembrolizumab (p=0.1856). 5-Fu in xenograft tumours of nude mice were evaluated.
Conclusion: For PD-L1 combined positive score, digital image analysis Results: BIO increased β-catenin expression, accompany with upregu-
and pathologists’ interpretation showed concordant results in most cases lation of TCF12, Caveolin-1, MRPs and downregulation of apoptosis
and the prognostic predictabilities were not significantly different. Digital induced by 5-Fu in CRC cells. Conversely, XAV939 decreased β-catenin,
evaluation PD-L1 would reduce scoring variability and may facilitate accompany with downregulation of TCF12, Caveolin-1, MRPs and up-
stratification of cancer patients in clinical practice. regulation of apoptosis induced by 5-Fu in CRC cells. Caveolin-1 was
identificated as an important downstream gene of WNT/β-catenin signal-
ling pathway. Caveolin-1 regulated the β-catenin, MRPs and apoptosis
PS-20-040 induced by 5-Fu. XAV939 reduced β-catenin and Caveolin-1, increased
When physicist helps pathologist: fluorimetry for differentiation be- apoptosis induced by 5-Fu and repressed xenograft tumour growth.
tween high-grade dysplasia and early colonic adenocarcinoma on Conclusion: WNT/β-catenin regulates chemoresistance of CRC cells by
hystologycal sections targeting the downstream gene Caveolin-1. The inhibition of WNT/β-
Y. Korneva1, V. Maryakhina2, A. Dorosevich1 catenin/TCF12/Caveolin-1 provides a new promising therapeutic strategy
1
Smolensk Regional Institute of Pathology, Russia, 2 Kumertau Branch for CRC treatment.
of Orenburg State University, Russia

Background & Objectives: Currently there is no objective method to PS-20-042

distinguish the early onset of invasive adenocarcinoma within adenoma- Predictive value of the high-risk histopathological criteria in
tous colonic polyps with high-grade dysplasia. appendiceal neuroendocrine tumours and their correlation with
Aim: To create objective method for differentiation on histologycal sec- lymph node status in additional right hemicolectomy
tions high-grade dysplasia form early adenocarcinoma, basing on bio- R. Loveikyte1, B. van Etten2, P. Hemmer2, A. Walenkamp3, G. Kats-
chemical changes in the tissues, cased by malignant transformation. Ugurlu1
1
Methods: Autofluorescence excitation of unstained dewaxed histological Department of Pathology and Medical Biology, University of
sections from our sample groups were measured on a spectrofluorimeter Groningen, University Medical Center Groningen, The Netherlands,
2
(SOLAR CM-2203). The wavelength of registration was 410 nm after its Department of Surgery, University of Groningen, University Medical
excitation in the UV region. Our sample groups consisted of 11 cases of Center Groningen, The Netherlands, 3 Department of Medical Oncology,
invasive adenocarcinomas (AC), 51 were adenomas with various grades University of Groningen, University Medical Center Groningen,
of dysplasia (41 tubular adenomas / 10 tubulovilllous adenomas) and 13 The Netherlands
were normal colonic mucosa.
Results: All the measured spectra have 2 maxima – 1st at 260-270 nm Background & Objectives: Appendectomy is the standard treatment for
(defined by tryptophan-containing peptides) and the 2nd at 330-340 nm appendiceal neuroendocrine tumours (aNETs). The recent European
(defined by collagen and NADH), but the relation between this maxima Neuroendocrine Tumour Society (ENETS) guidelines advocate addition-
depends on the type of pathological process. The greatest maxima ratio al right hemicolectomy for aNETs with high-risk for lymph node metas-
has normal mucosa (1,46 and more), ratios for tubular and tubulo-villous tasis based on their size, grade, location, resection margin,
adenomas are almost the same (1,35-1,45 and 1,26-1,35 respectively) and (lympho-)vascular invasion, and mesoappendiceal invasion.
depend on grade of dysplasia. The smallest ratio is for AC (1,13-1,25). Our aim was to evaluate the ability of the current ENETs histopatholog-
Conclusion: If the ratio between maxima of the spectra of autofluores- ical criteria to indicate patients with high-risk aNETs in the appendectomy
cence excitation form the histologycal section of colonic tumour is more specimens, and to predict the presence of lymph node metastasis in addi-
than 1,26, the case is considered to be adenoma with high dysplasia, if tional right hemicolectomy specimens.
1,25 and less – as AC, that may help to objectify the diagnostic of early Methods: We conducted a retrospective database pilot study. Using
malignant transformation of the adenoma on histologycal sections. Laboratorium Management System we identified thirteen patients with
well-differentiated aNETs with high-risk histopathological features who
underwent both appendectomy and right hemicolectomy. There was no
PS-20-041 age restriction.
Stabilising and upregulating Axin by Tankyrase inhibitior reverses Results: Three of the 13 patients had lymph node metastasis. All 3 primary
5-fluorouracil chemoresistance through inhibition of WNT/Caveolin- tumours were <2cm (range: 1.3 – 1.7cm) and showed >3mm mesoappendiceal
1 in colorectal cancer cells invasion. One patient without metastasis showed > 3mm mesoaapendiceal
K. Liu1, J. Li1 invasion. Five other patients had tumours ≥2cm (range: 2 – 3.6cm) and none
1
Department of Pathology, the Sixth Affiliated Hospital of Guangzhou of them had positive lymph nodes. (Lympho-)vascular invasion was found in
Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong, patients with and without lymph node metastasis. The positive predictive value
China of the current histopathological criteria is 23%.
Conclusion: This retrospective analysis indicates that the current ENETS
Background & Objectives: Colorectal cancer (CRC) is a common ma- histopathological criteria may not be the best predictor of lymph node
lignant tumour, 5-Fluorouracil (5-Fu) and its derivatives are commonly metastasis in the additional right hemicolectomy. Among the high-risk
used in the chemotherapy of CRC, but resistance to chemotherapy is one criteria mesoappendiceal invasion of >3mm was the best predictor of
of main obstacles for CRC treatment. In present study, we evaluated lymph node metastasis. Further studies are needed to evaluate if
effects and mechanisms of WNT/β-catenin/Caveolin-1 signalling path- mesoappendiceal invasion could be used as an independent high-risk
way on drug resistance of CRC. criterion.
Virchows Arch

PS-20-043 aggregate formation 66.7%. Average sample areas were similar in both
c-Myc as a key-marker in the colorectal cancer resistance to EGFR groups, whereas digital image analysis showed significantly higher EoL/
inhibitors mm2 count in both epithelial (171.2±177.2 vs 3.3±11.6) and subepithelial
M. Martini1, A. Strippoli2, A. Cocomazzi3, T. Cenci3, M. Basso2, L.M. (61.01±67.1 vs 4.5±13.2) compartments of EoE versus GERD patients.
Larocca3 ROC-analysis found a reliable threshold for differentiating EoE from
1
Institute of Pathology, Italy, 2 Fondazione Policlinico Universitario A. GERD at 33 EoL/mm2 in epithelial and 16 EoL/mm2 in subepithelial
Gemelli IRCCS, Italy, 3 Institute of Pathology, Università Cattolica del compartment.
Sacro Cuore, Rome, Italy Conclusion: Last October an international guideline firstly suggested,
instead of EoL/HPF, an estimated 60 EoL/mm2 threshold for diagnosing
Background & Objectives: Despite the outstanding success of EGFR EoE. Our study with numerical counting of EoLs on a digital platform
inhibitors in the treatment of metastatic colorectal cancer (mCC), targeted found that lower, 33EoL/mm2 threshold reliably detects EoE.
therapy (TT) leads inevitably to the acquired resistance stemming from
various molecular mechanisms such as activation of compensatory ki-
nases. Alterations in the transcriptional factor c-Myc, a downstream ef- PS-20-045
fector of several kinase pathways, could be also involved in the TT Assessment of gastric mucosal atrophy: from consensus estimation to
resistance. the development of a decision support system
Methods: The expression of c-Myc was assessed in 121 RAS and BRAF S. Mozgovoi1, A. Shimanskaya1, A. Kononov1, M. Parygina1, I.
wild type mCC samples before treatment with anti-EGFR+Folfiri therapy Ostroglyadova1
1
and in 33 subsequent metastases collected during TT or in TT resistance Omsk State Medical University, Russia
phase. In this cohort, and in two cancer cell lines, we also analysed the
expression of miRNA143 and miRNA145, using real-time assay, and we Background & Objectives: Atrophic gastritis increases the risk of
performed a c-Myc Targets PCR Array. Results were correlated with intestinal-type gastric cancer (adenocarcinoma). Semi-quantitative as-
clinical and pathological features. sessment of the level of atrophy is subjective, inappropriate endoscopic
Results: Low c-Myc expression patients showed a significant higher PFS technology makes it impossible to use traditional approaches.
and OS respect to those with high c-Myc expression (HME). HME pat- Methods: 98 diagnostic cases of chronic gastritis were selected. Analysis
tern was significantly associated to the anti-EGFR molecular resistance of the reproducibility of the assessment (inter-rater agreement) between
alterations. Moreover, restoring miRNA143 and miRNA145 expression 41 pathologists was carried out using kappa statistics (Cohen’s kappa) by
in two KRAS mutated cancer cell-lines, determined a c-Myc downregu- pair-wise comparison. The validity (sencitivity and specificity) of histo-
lation with a reduction of the cell proliferation and migration after expo- chemical techniques and biomolecular markers of atrophy and intestinal
sure to cetuximab. Several altered genes expression in HME mCC metaplasia (metaplastic atrophy) were assessed by special stains and im-
highlighted the role of c-Myc in CC-related cell cycle, apoptosis and cell munohistochemistry. 50 selected cases with kappa=1 between authors
growth pathways. were used as a "gold standard".
Conclusion: HME in anti-EGFR treated mCC might discriminate pa- Results: General unweighted κ before training was 0.23 (fair agreement).
tients with a lower PFS and OS. Moreover, the significant c-Myc associ- The level was maximal when marked atrophic changes was revealed. Low
ation to anti-EGFR resistance, also through some miRs alteration, and the values of the validity criterion in assessing routine histochemical character-
individuation of c-Myc activated genes suggest the c-Myc pathway istics were identified (confidence interval 0,53-0,85 for sensitivity). Three
blockade to prevent the kinome reprogramming mechanism. molecules with high validity as markers of metaplastic atrophy are identi-
fied: CDX-2 - nuclear transcription factor associated with intestinal differ-
This study was supported by Università Cattolica del Sacro Cuore, Fondi entiation, CD10 - a membrane mucin brush border and MUC2 - intestinal
d’Ateneo, Linea D1 (2016 and 2017; MM and LML). type mucin (confidence interval for all three markers 70-94, but up to 100%
at metaplastic athrophy). The algorithm for using markers to assess the
PS-20-044 grade of atrophy and the stage of chronic gastritis was proposed.
Eosinophilic oesophagitis: standardised diagnosis with digital pathol- Conclusion: The data obtained in our pilot study demonstrate the prob-
ogy platform lem of recognition and interpretation of atrophic changes detected in
C. Molnár1, T. Micsik2, Á. Patai1 biopsy specimens. At the same time, the introduction of a marker evalu-
1
Semmelweis University, Hungary, 2 1st Department of Pathology and ation method can significantly increase the degree of consistency in de-
Experimental Cancer Research, Semmelweis University, Budapest, cision making.
Hungary

Background & Objectives: Eosinophilic ooesophagitis (EoE) is a PS-20-046

chronic, antigen‐mediated disease causing severe dysphagia. Diagnosis Expression of miR-21 and its target protein PDCD4 in intestinal type
relies on clinical symptoms and eosinophil leukocytes (EoL) per High gastric cancer
Power Field (HPF), thought histology samples may not fill the whole S. Mozgovoi1, E. Pomorgailo1, A. Shimanskaya1, A. Kononov1, V.
objective and there is an almost 2,5-fold difference in HPF-area of differ- Rubtsov1, J. Fedotova1
ent microscopes. Thus, a standardised number of EoL/mm2 may decrease 1
Omsk State Medical University, Russia
diagnostic discrepancies and help towards better diagnostic rate.
Methods: 45 EoE and matched GERD cases were selected retrospective- Background & Objectives: The participation of miR-21 and its target
ly from the archives of the Pathology Departments of Semmelweis protein PDCD4 in key molecular mechanisms in carcinogenesis. The
University, Budapest, Hungary. Clinicopathological data were collected, mail purpose was assessment of the level of oncogenic miR-21 and its
slides were digitized using PannoramicTM P250 Flash digital slide scan- target - PDCD4 regulatory protein in gastric cancer.
ner (3DHISTECH Ltd., Budapest, Hungary). Epithelial and subepithelial Methods: The subjects of the study were 40 biopsy specimens with a
compartments and EoLs were annotated digitally with CaseViewer. histological features of chronic atrophic gastritis and fragments of 45
Results: The 45 EoE patients were 66% males; mean age was 23.5 ± 19.7 stomachs resected for intestinal type adenocarcinoma. The assessment
years. Most common endoscopic EoE-manifestations were rings (36.8%), of the PDCD4 protein was carried out by semi-quantitative immunohis-
longitudinal furrows (21.1%). Histopathologic EoE-findings were: eosin- tochemical scale. The amount of miR-21 was determined by stem-loop
ophilic cell degranulation 86.6%, spongiosis 75.5%, eosinophilic real-time PCR in paraffin sections using specific miR-21 primers.
 Virchows Arch

Descriptive statistics of groups are presented in the form of a median and Background & Objectives: Screening for early detection of colo-
interquartile latitude. rectal malignancies has demonstrated efficacy in reducing disease-
Results: The expression of miR in chronic gastritis within the distant specific mortality. Current surveillance guidelines recommend a 3-
zone of gastric cancer (225.69; from 101.05 to 280.67), adenocarcinoma year follow-up colonoscopy after resection of high-risk adenomas
stomach (378.65; from 103.16 to 375.12) were increased. The difference (HRA), defined by multiplicity (three or more) or advanced le-
between the distant zone of gastric cancer and samples with a similar sions (>1cm in diameter, villous component and/or high-grade
histological pattern, but without association with gastric cancer, was sig- dysplasia. However, this recommendation is exclusively based on
nificant (p = 0.00046). PDCD4 was showed decrease (p = 0.00001) in the endoscopical and histological criteria.
level of PDCD4 in the tissues of intestinal adenocarcinoma (4; from 2 to Methods: The aim of this study was to evaluate immunohistochemical
6) compared to the distant zone group (9; from 9 to 12). , There was no expression of different markers, to perform a molecular analysis in HRA
statistically significant difference after comparing chronic gastritis in bi- of a large cohort of patients whom underwent surveillance colonoscopy,
opsy specimens (10; from 9 to 10) with a group of chronic gastritis in the and to determine their association with recurrence. Serrated lesions and
distant zone of gastric cancer. adenomas with high-grade dysplasia were excluded in this cohort to be
Conclusion: The study shows that miR-21 and its target protein PDCD4 further analysed. Among 638 patients with a prior diagnosis of HRA, a
are promising markers for assessing the risk of development, early diag- total of 518 underwent a 3-year follow-up colonoscopy in our Institution.
nosis of intestinal type gastric cancer. We selected the biggest lesions in those cases with multiplicity and cre-
ated a tissue micro-array with 479 samples. Immunostains for p53, MLH-
1, beta-catenin, CDX-2, Ki-67, keratin 7 and keratin 20 were performed
PS-20-047 and evaluated. There was enough remaining material in 389 cases to
Detection of tissue patterns, their immunohistochemical signatures perform mutational analysis. A sampler library was generated from the
and biomarkers of inflammation in the gastric mucosa as a system DNA extracted with a QIAseq Targeted DNA panel (Qiagen) containing
of personalised prediction of sporadic gastric cancer the coding region of genes KRAS, NRAS, BRAF, APC, TP53, FBXW7,
S. Mozgovoi1, A. Shimanskaya1, A. Kononov1, E. Pomorgailo1, V. CTNNB1 and SMAD4. The resulting library was sequenced on a NGS
Rubtsov1, L. Panyushkin2, M. Parygina1 platform MiSeq® (Illumina).
1
Omsk State Medical University, Russia, 2 West Siberian Medical Center Results: As expected, the molecular analysis revealed a high prevalence
FMBA of Russia of different pathogenic mutations involving APC and other genes,
althought no significant statistical association was observed between
Background & Objectives: Correa’s cascade is fundamental basis of any of the immunomarkers and neither with the genes evaluated. Only
gastric cancer prevention, and stomach mucosal atrophy in con- advanced age was statistically associated with higher risk of recurrence in
junction with intestinal metaplasia will be considered as a non- the follow-up colonoscopy (p <0.05). Remarkably, trend was observed
return point in the cascade of carcinogenesis. between the risk of recurrence in the surveillance colonoscopy and the
Methods: The problem is that the detection of atrophy by the interna- presence of partial loses of immunohistochemical expression of MLH-1
tional system requires scrupulous adherence to the protocol for obtaining and the detection of SMAD4 mutations.
biopsy specimens from 5 points of the gastric mucosa, which turns out to Conclusion: No distinct immunohistochemical nor genetic patterns relat-
be a problem for the practitioner. According to our data, the protocol is ed to recurrence of HRA in the surveillance colonoscopy were identified
observed in 4.0% of endoscopic studies. Therefore, we need a search for in our study. However, we identified some immunohistochemical and
other ways to personalize the risk of gastric cancer. molecular trends that might become an independent variant for individu-
Results: Immunohistochemical detection of intestinal differentiation alized surveillance strategies in the future, although further investigation
proteins allows for earlier and more reliable determination of meta- in required.
plastic atrophy in the gastric mucosa. The immunohistochemical
signature of metaplastic atrophy with the calculation of the sensi-
tivity and specificity of immunohistochemical markers reliably PS-20-049
identifies atrophy, which determines the risk of developing gastric Prognostic value of CD8 Immunogradient indicators in tumour-
cancer, and not by 5, but by 2-3 biopsy specimens. stroma interface zone of colorectal cancer
In order to increase the predictability of the system by molecular profiling A. Nestarenkaitė1,2, A. Rasmusson1,2, D. Zilenaite1,2, R. Augulis1,2,3, A.
of miRNAs that regulate the physiological manifestation of genes from Laurinaviciene1,2, V. Ostapenko4, T. Poskus5, A. Laurinavicius1,2
1
both the inflammatory response and those involved in carcinogenesis, National Center of Pathology, affiliate of Vilnius University Hospital
molecules were selected. Their aberrant expression rom superficial gas- Santaros Clinics, Lithuania, 2 Department of Pathology, Forensic
tritis to atrophic background of sporadic cancer in increased. The level of Medicine and Pharmacology, Institute of Biomedical Sciences of the
research in this direction is still pilot. Faculty of Medicine of Vilnius University, Lithuania, 3 Institute of
Conclusion: The results suggest that combinations of a panel of bio- Biosciences, Life Sciences Centre, Vilnius University, Lithuania,
4
markers of inflammation and tissue pattern monitoring can be a valid National Cancer Institute, Vilnius, Lithuania, 5 Institute of Clinical
system for personalised assessment of the risk of developing gastric ad- Medicine, Faculty of Medicine, Vilnius University, Lithuania
enocarcinoma.
Background & Objectives: The immune response within the tumour
microenvironment assessment methods were proposed to predict patient
PS-20-048 survival and therapy outcomes in colorectal (CRC) and other cancers;
Looking for an immunohistochemical / molecular predictor of recur- nevertheless, automated operator-independent approaches are lacking.
rence in the surveillance colonoscopy after resection of colorectal We present a new image analysis method to automatically extract
high-risk adenomas Immunogradient indicators and their prognostic value in CRC patients.
D. Naranjo-Hans1, M. Iglesias2, G. Navarro1, J. Gimeno3, J. Masso1, L. Methods: Surgically excised CRC samples from 101 patients were
Carot4, C. Alvarez-Urturi4, X. Duran5, M. Andreu4, B. Lloveras3 stained for CD8, scanned, and analysed by Indica Labs' HALOTM soft-
1
Pathology Department. Hospital del Mar, Spain, 2 Pathology ware. The image analysis data was then subsampled by a hexagonal grid
Department, Hospital del Mar, Spain, 3 Hospital del Mar, Spain, which was used to extract and rank the tumour interface zone (IZ) ac-
4
Gastroenterology Department. Hospital del Mar, Spain, 5 Institute cording to distance to the tumour edge. Lastly, a set of novel
Hospital del Mar d'Investigacions Mèdiques, Spain Immunogradient indicators representing CD8 cell density profiles across
Virchows Arch

1
the IZ were computed. The prognostic value of the indicators was tested Molecular Histology, Bioneer AS, Denmark, 2 University Institute of
by univariate and multiple survival statistics. Pathology, Aarhus University Hospital, Denmark, 3 Department of
Results: The Immunogradient indicators Immunodrop (ID) and Centre of Clinical Pathology, Vejle Hospital, Part of Lillebaelt Hospital, Denmark
Mass (CM) for the CD8 cells, as well as CD8 cell densities within tumour
and stroma aspects of the IZ and their factor scores provided significant Background & Objectives: MicroRNA-21 (miR-21) is upregulated
stratifications of CRC patients into prognostic groups (p<0.05). Multiple in many cancer types including colorectal cancers (CRC) and is a
Cox regression analyses of extracted indicators along with conventional prognostic indicator of recurrence and poor prognosis. In CRC,
clinicopathologic characteristics revealed ID and the Aggregated IZ CD8 miR-21 is highly expressed in stromal fibroblastic cells and more
cell response factor as strong independent predictors of worse (HR: 2.41, weakly in a subset of budding cancer cells. Exploration of the
p=0.0126) and better (HR: 0.41, p=0.0196) 5-year overall survival, expression of inflammatory markers in CRC using RNAscope
respectively. probe technology, revealed tumour necrosis factor alpha (TNF-α)
Conclusion: The proposed automated, data-driven digital image analysis in cancer cells with characteristics of both branching and budding.
method for the IZ immune infiltrate assessment provides strong indepen- We hypothesized that miR-21 may protect both fibroblasts and
dent prognostic biomarkers of anti-tumour immune response in CRC. cancer cells from cell death directed by TNF-α. The aim of this
The method is operator-independent and is based on single CD8 immu- study was therefore to analyse the presence of miR-21 and
nohistochemistry slides. TNF-α mRNA expression at the invasive front of CRC.
Methods: We established an automated multiplex procedure on a
This research was funded by the European Social Fund according to the Ventana instrument for the co-staining of miR-21, TNF-α mRNA and
activity “Improvement of researchers’ qualification by implementing cytokeratin in frozen CRC samples (n=4) with evident cancer cell bud-
world-class R&D projects”, No. 09.3.3-LMT-K-712. ding. Digital whole slides were obtained using a Pannoramic confocal
slide scanner.
Results: In all of four cases, TNF-α mRNA was seen in a small subset of
PS-20-050 cancer cells at the invasive front. Both co-expression and lack of co-
Epithelial-mesenchymal transition markers, MMP2 and MMP9 - expression of miR-21 and TNF-α in the branching and budding cancer
comparative study in poorly cohesive versus intestinal type gastric cells was noted, suggesting non-correlated expression. miR-21-positive
adenocarcinoma fibroblastic cells were all TNF-α negative and not always associated with
M. Niculae1, A. Ienea2, M. Farcas2, C. Popp2,3 TNF-α positive cancer cells.
1
Spitalul Clinic Colentina Bucuresti, Romania, 2 Spitalul Clinic Conclusion: miR-21 and TNF-α mRNA are often co-expressed,
Colentina Bucuresti, Romania, 3 UMF Carol Davila Bucuresti, Romania but not co-regulated, in a subset of cancer cells with branching
or budding characteristics. The implications of these findings for
Background & Objectives: Multiple epithelial-mesenchymal transi- the local tumour growth at the invasive front will be discussed.
tion (EMT) molecules, as well as different matrix metalloproteases
are involved in gastric tumourigenesis and evolution. Epithelial-
mesenchymal transition, intercellular adhesion and proteolytic pro- PS-20-052
cesses are associated with normal and pathological migration of Altered linkage pattern of N-glycan sialic acids in pseudomyxoma
cells, having a significant impact on gastric adenocarcinoma pa- peritonei
tients’ outcome. The aim of this study is comparative analysis of P. Nummela1, A. Heiskanen2, H. Leinonen1, C. Haglund3,4, A. Lepistö3,
E-cadherin, N-cadherin, SNAIL, MMP2 and MMP9 in poorly co- T. Satomaa2, A. Ristimäki1,5
1
hesive versus intestinal type gastric adenocarcinoma, in order to Applied Tumour Genomics Research Program, Faculty of Medicine,
identify immunohistochemical patterns for stratifying patients in University of Helsinki, Finland, 2 Glykos Finland Ltd., Helsinki, Finland,
3
different prognosis groups. Department of Surgery, Helsinki University Hospital, Finland,
4
Methods: We conducted a retrospective study including 50 consecutive Translational Cancer Medicine Research Program, Faculty of
cases of gastric tumours (25 poorly cohesive and 25 intestinal type). We Medicine, University of Helsinki, Finland, 5 Department of Pathology,
performed SNAIL, E-cadherin, N-cadherin, MMP2 and MMP9 on rep- HUSLAB, Helsinki University Hospital and University of Helsinki,
resentative samples from gastrectomy specimens included in multi-tissue Finland
blocks.
Results: SNAIL was expressed in about 65% of poorly cohesive and in Background & Objectives: Cancer cells often show glycosylation alter-
only 10% of intestinal type gastric adenocarcinomas, correlated with loss ations, such as increased sialylation and fucosylation, which may provide
of expression for cadherins. MMP2 and MMP9 were more frequent and new biomarkers and therapy targets. We have recently reported highly
intensely expressed in poorly cohesive adenocarcinomas, a significant increased N-glycan fucosylation in pseudomyxoma peritonei (PMP), but
difference being observed for MMP9 (80% in intestinal type versus could not identify alteration in overall sialylation. Here, we utilized more
40% in poorly cohesive type). detailed analyses to study the linkage pattern of N-glycan sialic acids in
Conclusion: Expression of SNAIL and MMP2 and 9 was higher in PMP as compared to normal appendices.
poorly cohesive gastric adenocarcinomas than in intestinal type Methods: We extracted acidic N-glycans from formalin-fixed, paraffin-
ones, correlated with a loss of cell adhesion markers. These data embedded tissue specimens of normal appendices, low-grade appendiceal
are indicating the importance of EMT and MMP evaluation in mucinous neoplasms (LAMNs), and low-grade and high-grade PMPs
gastric cancer, as well as the potential of these molecules to (n=4 in each group), and analysed their sialic acid linkage pattern by ethyl
become therapeuthical targets (as MMP9 is already used) for ad- esterification or sialidase digestion (alpha2,3- vs. total sialidase) com-
juvant treatments. bined with mass spectrometry.
Results: Sialylation was the predominant acidic modification (>90%) of
the analysed N-glycans. With the used methods, we could further divide
PS-20-051 the sialylated glycan structures into two subclasses: alpha2,3- or alpha2,6-
Co-expression analysis of microRNA-21 and TNF-alpha mRNA in sialylated, according to the sialic acid linkage type. When comparing
budding cancer cells in colorectal cancer these subclasses, the N-glycans of PMP tumours showed higher propor-
B. Nielsen1, T. Møller1, J. P James1, K. Holmstrøm1, F. B Sørensen2, J. tion of alpha2,6- than alpha2,3-sialylated glycans, whereas control appen-
Lindebjreg3 dices and LAMNs had the opposite pattern.
 Virchows Arch

Conclusion: Although overall sialylation seems to be unchanged in PMP dose at 6 hours) and IV=CLP + faecal microbiota transplantation(FMT
tumours, they contain increased proportion of alpha2,6-linked sialic from healthy donors at 6 hours by nasogastric tube)(n=10). At 24 hours,
acids. Previously, increased alpha2,6-sialylation has been reported in sev- ileal tissues from experimental animals were harvested for histological
eral cancers, and has been associated with cancer cell adhesion, migra- analyses (mucosal/villous architectural characteristics, mitotic/apoptotic
tion, invasion and therapeutic resistance. counts, occludin expression and lymphocytic infiltration). In a second
experiment the same groups were observed for seven days for mortality,
with daily administration of hydrocortisone (group III) and FMT (group
PS-20-053 IV) in surviving rats of these groups.
Gastrointestinal carcinomas with rhabdoide features: clinicopatho- Results: Compared to sham, the septic rats(group II) showed reduced
logic, immunohistochemical, and molecular study of a series of 9 mucosal thickness (P<0.05), villous density and height (P<0.001),
cases mitotic/apoptotic ratio (P<0.001) and increased apoptosis (P<0.001),
A. Panizo1, C. Llanos1, M. Garcia-Martos2, D. Guerrero1, Y. Rodriguez1, lymphocytic inlfiltration and intraepithelial CD3+T-lymphocytes
M. Gomez-Dorronsoro1 (P<0.001). Hydrocortisone(group III) or FMT(group IV) significantly
1
Complejo Hospitalario de Navarra, Spain, 2 Hospital Universitario de ameliorated 7 days survival (P<0.001), mucosal atrophy (P<0.001), vil-
Torrejon, Spain lous blunting (P<0.001 and P<0.01), intraepithelial T-lymphocytes
(P<0.001) and apoptosis (P<0.05 and P<0.001), while increased paneth
Background & Objectives: Neoplasms with rhabdoid features (RF) cells (P<0.05, P<0.01) and mitotic/apoptotic ratio (P<0.05, P<0.001). In
have been reported in many sites. Gastrointestinal (GI) cancers with RF the CLP group occludin expression in intestinal cells was significantly
are extremely rare. decreased (P<0.01 vs group I) while increased in groups III and IV
Methods: We studied 9 GI carcinomas with RF. Clinicopathological and (P<0.01 vs group II).
IHC analysis: cytokeratins, vimentin, myogenic markers, mismatch repair Conclusion: Faecal microbiota transplantation and low dose hydrocorti-
proteins (MMRp), CDX2, SMARCB1-INI1, p53, and Ki-67. KRAS mu- sone administration ameliorate gut barrier dysfunction in polymicrobial
tations were studied by real-time PCR. sepsis in rats leading to improved survival.
Results: Four patients male and 5 female: mean age 70 yrs. (range 50-81
yrs.). Location: stomach (2), duodenum (1), and colon (right: 3; left: 1;
sigma: 2). Mean size: 7,5 cm. All but two tumours were pT4 (remaining: PS-20-055
pT3). All cases revealed a glandular component (6 poorly-differentiated, Immune Checkpoint Inhibitors (ICPIs)-induced granulomatous
2 moderate, and 1 signet-ring). Rhabdoid areas ranged from 30% to 80%. colitis
All but one case had lymph node metastasis (pN1: 5; pN2: 2; and pN3: 1). D. Pouloudi1, D. Kamberoglou2, H. Gogas3, S. Sakellariou1
1
One case: liver metastasis at presentation. Rhabdoid areas were positive First Department of Pathology, Medical School, National and
for cytokeratin, and vimentin, and negative for CDX2, myogenic Kapodistrian University of Athens, Greece, 2 Deptartment of
markers. Ki-67 and p53 in the RF were higher than in the non-rhabdoid. Gastroenterology, Laiko General Hospital, Medical School, National
All cases had intact nuclear expression for MMRp. One case had KRAS and Kapodistrian University of Athens, Greece, 3 First Department of
mutation at codon 13 exon 2. One case had loss of SMARCB1-INI1 Internal Medicine, Laiko General Hospital, Medical School, National
protein expression. Follow-up available in 8 cases (median follow-up: and Kapodistrian University of Athens, Greece
3,5 months; range 0,1-181): 3 patients were alive and well, 2 died without
disease, and 3 died due to progression. Background & Objectives: Among immune checkpoint inhibitors
Conclusion: We described 9 new GI neoplasms with RF with co- (ICPIs), anti-PD1 regimens are the immunomodulating treatment of
expression of vimentin and cytokeratin, and no relationship with micro- choice for malignant melanoma. Ιpilimumab, an anti-CTLA-4 ICPI, is
satellite-instability. The RF represents a distinctive pathway of dediffer- currently administrated in combination schemes or as second-line treat-
entiation. Recognition of RF in GI tumours is important because of their ment. ICPIs can cause serious immune-related side effects such as severe
aggressive clinical course. colitis, dermatitis, thyroiditis, hypophysitis and hepatitis.
Methods: A 63-year-old female patient on anti-PD1 and ipilimumab for
metastatic melanoma presented with fever and persistent diarrhea.
PS-20-054 Biopsies from endoscopically edematous, hyperemic and eroded sigmoid
Faecal microbiota transplantation and hydrocortisone ameliorate in- colon mucosa revealed many small epithelioid granulomas within the
testinal barrier dysfunction and improve survival in a rat model of crypts with partial or complete destruction of crypt epithelium. A moder-
cecal ligation and puncture-induced sepsis ate degree of lymphoplasmacytic inflammation with few eosinophils and
I. Papadopoulou1, D. Bantouna2, I. Maroulis3, C. Gogos4, V. Zolota5, S. neutrophils and rare crypt abscesses coexisted. Histological findings were
Assimakopoulos6 compatible with granulomatous colitis probably related to ICPIs therapy.
1
Department of Gastroenterology, Metaxa Cancer Hospital of Piraeus, Results: ICPIs-induced colitis usually presents as active colitis
Greece, 2 Department of Pathology, Medical School, University of Patras, characterised by lymphoplasmacytic lamina propria expansion accompa-
Greece, 3 Department of Surgery, Medical School, University of Patras, nied by neutrophils with cryptitis and crypt microabscesses. Significant
Greece, 4 Department of Internal Medicine, Medical School, University apoptosis at the crypt base, intraepithelial lymphocytosis resembling lym-
of Patras, Greece, 5 Department of Pathology, Medical School, University phocytic colitis and progression to active chronic colitis mimicking in-
of Patras, Greece, 6 Department of Internal Medicine, Medical School, flammatory bowel disease have also been reported.
University of Patras, Greece Current literature refers to granulomas associated with ruptured crypts in
5-18% of anti-PD1 but not anti-CTLA-4 related colitis. Additionally,
Background & Objectives: Sepsis is associated with high mortality and post-immunotherapy sarcoid-like reaction in lymph nodes and skin, gran-
intestinal barrier failure motors the systemic inflammatory response. ulomatous interstitial nephritis and hepatic fibrin ring granulomas have
Early administration of low dose hydrocortisone in septic shock has been been reported. It seems that ICPIs can induce a cell-mediated immune
shown to increase survival, while faecal microbiota transplantation re- granulomatous reaction.
verses intestinal barrier dysfunction. Conclusion: Awareness of this rare histologic manifestation of ICPIs-
Methods: Forty adults male Wistar rats were randomly divided into four induced colitis can help to avoid misdiagnosis. The diversity of histolog-
groups: I=sham(n=10), II=cecal ligation and puncture(CLP)(n=10), ical subtypes points towards complex immune mechanisms and possible
III=CLP + hydrocortisone(n=10)(2.8 mg/kg/d, intraperitoneally single synergistic factors and may reflect treatment response.
Virchows Arch

PS-20-057 Conclusion: These results indicate that the expression of claspin might be
Syntaxin - a novel robust neuroendocrine marker a key regulator in the progression of GC and might play an important role
A. Sejben1, S. Turkevi-Nagy1, Z. Fekete1, B. Kővári1 in CSCs of GC.
1
University of Szeged, Hungary

Background & Objectives: Although typical neuroendocrine tumours PS-20-059

(NET) and neuroendocrine carcinomas (NEC) have characteristic mor- Influence of histopathological factors on cancer-specific survival of
phology, considering the specific clinical management of neuroendocrine patients with stage II colorrectal carcinoma that later became stage
neoplasms (NEN) immunohistochemistry is needed to confirm the diag- IV
nosis. For this purpose synaptophysin and chromogranin-A are most A. Sobrino Prados1, R.I. Bermudez Cameo1, C. Hörndler Argarate2, E.
frequently used. The sensitivity and specificity of these classic neuroen- del Valle Sánchez2, A. Puertas Canteria2, M.Á. Trigo Cebrián2, L.A.
docrine markers are not perfect. Syntaxins are a family of membrane- Ligorred Padilla2, M.J. Viso Soriano1, J.I. Franco Rubio2, S. Bakali
integrated proteins involved in neuromediator release. So far syntaxin Badesa1, H.P. Almanzar Comas1, Á. Arellano Álvarez1, N. Estrada
expression was only reported in neuronal tissues, therefore syntaxin im- Mallarino1
1
munohistochemistry is potentially a highly specific method to demon- Hospital Universitario Miguel Servet Zaragoza, Spain, 2 Hospital
strate neuroendocrine differentiation. Universitario Miguel Servet, Spain
Methods: Syntaxin-1A, synaptophysin and chromogranin-A expression were
analysed by immunohistochemistry in gastroenteropancreatic NETs and NECs. Background & Objectives: Patients with colon carcinoma (CC) may
To investigate the specificity of this novel marker, a variety of carcinomas develop recurrence/metastasis, even in a stage II. We consider necessary
including gastrointestinal, pulmonary, breast, female genital, skin, liver, kidney, to identify histological findings related with tumour progression.
thyroid, parathyroid, and adrenocortical tumours were also tested. Methods: Patients with CC operated in stage II between 2008 and /2012
Results: Strong and diffuse membranous syntaxin-1A expression was were evaluated. Patients with change from stage II to IV were compared
observed in 59/60NETs, while moderate to strong membranous expres- by Kaplan-Meier curves. Several histopathological factors were analysed,
sion was documented in 15/15 NECs. In all NECs at least 50% of tumour including the level of invasion, the presence of “tumour budding” and
cells were labelled (average: 80%). The sensitivity of syntaxin-1A (98%) peritumoural desmoplastic stroma. For statistical analysis we used
in NETs was similar to synaptophysin (96%) and chromogranin-A (93%), Student-t test, Fisher test and Mann-Whitney U. Univariate and multivar-
whereas syntaxin-1A (100%) had somewhat higher sensitivity in NECs iate analysis were also performed using Cox regression. We found 147
compared to synaptophysin (91%) and chromogranin-A (89%). The var- patients with CC operated in stage II, and 30.3% had tumoural progres-
ious types of non-neuroendocrine neoplasms were uniformly negative for sion from stage II to IV. The conditions that we found related to adverse
syntaxin-1A. prognosis were high histological grade (p=0.04), lympho-vascular inva-
Conclusion: Syntaxin-1 is a robust neuroendocrine marker with excellent sion (p<0.001), perineural invasion (p=0.04), tumour budding (p=0.02)
sensitivity and specificity. Syntaxin-1 is expressed regardless of tumour and the presence of marked peritumoural stroma (p=0.004).
grade, with usually a diffuse positivity even in NECs and rectal L-cell Results: When comparing the characteristics of patients with CC who
tumours. Compared to classic cytoplasmic markers, the membranous changed from stage II to stage IV, besides the advanced level of invasion
staining pattern can be more reliably interpreted in routine histopathology. worsening the prognosis, we found the overall 5-year survival of patients
with presence of pronounced peritumoural stroma and high "tumour bud-
Supported by University of Szeged, Faculty of Medicine Research Fund ding" was significantly lower than those patients without any of these
– Hetényi Géza grant, 5S582. histological factors. The prognostic factors described can help to recog-
nize which patients at high risk of recurrence could benefit from
chemotherapy.
PS-20-058 Conclusion: Some histopathological factors, like tumour budding and
Clinicopathological significance of claspin overexpression and its as- peritumoural desmoplastic stroma, may have a great relevance in patients’
sociation with spheroid formation in gastric cancer evolution. Therefore, further research is needed to provide the best treat-
K. Sentani1, G. Kobayashi2, T. Imai1, N. Oue1, N. Sasaki2, W. Yasui1 ment options according to these characteristics.
1
Department of Molecular Pathology, Graduate School of Biomedical
and Health Sciences, Hiroshima University, Japan, 2 Department of
Pathology, Kure-Kyosai Hospital, Federation of National Public Service PS-20-060
Personnel Mutual Aid Associations, Japan The role of additional stainings in the assessment of the Peritoneal
Regression Grading Score (PRGS) in peritoneal metastasis from gas-
Background & Objectives: Gastric cancer (GC) is one of the leading tric origin
causes of cancer-related death worldwide. Spheroid colony formation is a W. Solass1, D. Nann1, J. Steinke1, D. Westerwick1, G. Nadiradze2, K.
useful method to identify cancer stem cells (CSCs). The aim of this study Thiel2, P. Horvath2, R. Archid2, H. Bösmüller1
1
was to identify a novel prognostic marker or therapeutic target for GC Institute of Pathology and Neuropathology, University Hospital
using a method to identify CSCs. Tuebingen, Eberhard-Karls-University Tuebingen, Germany, 2
Methods: We analysed the microarray data in spheroid body-forming Department of General and Transplant Surgery, University Hospital
and parental cells and focused on the CLSPN gene because it is Tuebingen, Eberhard-Karls-University Tuebingen, Germany
overexpressed in the spheroid body-forming cells in both the GC cell
lines MKN-45 and MKN-74. Background & Objectives: The Peritoneal Regression Grading Score
Results: RT-PCR analysis revealed that CLSPN mRNA expression was (PRGS), proposed in 2016 by a group of European pathologists, is a 4 tied
upregulated in GC cell lines MKN-45, MKN-74, and TMK-1. regression grading score for peritoneal metastasis (PM) of various origins.
Immunohistochemistry of claspin showed that 94 (47%) of 203 GC cases Reproducibility of PRGS has been validated in a multicentric compara-
were positive. Claspin-positive GC cases were associated with higher T and tive study. As other regression scores, PRGS is based on the evaluation of
N grades, tumour stage, lymphatic invasion and poor prognosis. In addition, HE-stained biopsies. A potential added value of supplementary stainings
claspin expression was co-expressed with CD44, human epidermal growth or immunohistochemistry (IHC) is unclear.
factor receptor type 2 (HER2) and p53. CLSPN small interfering RNA Methods: Retrospective analysis of 339 biopsies obtained during
(siRNA) treatment decreased GC cell proliferation and invasion. 76 laparoscopies in 33 patients with PM of gastric origin. PRGS
 Virchows Arch

was determined based on HE-staining by an independent patholo- (myofibroblasts) are present in high frequency in the tumour microenvi-
gist. In a 2nd round all biopsies classified as PRGS 1 (no residual ronment. Indicating that in a tumour microenvironment, the surrounding
tumour) or “uncertain” were re-evaluated in PAS-stain. In a 3rd stromal tissue can be transformed, acquiring an abnormal phenotype with
round all PRGS1 and “remaining uncertain” cases were scored in modification of the metabolism of resident cells.
IHC with BerEP4-stain.
Results: After HE staining, 95/339 biopsies (28%) were classified as
PRGS1. Additional PAS staining confirmed scoring in 74/95 biopsies, PS-20-062
in 10/95 biopsies were upgraded to PRGS 2 and 11/95 classified as Interobserver concordance of tumour-stroma ratio estimative
“uncertain”. After further BerEp4 staining, score was confirmed in 6/11 R.M. Souza da Silva1, E. Moreira Queiroga2, A. Rolim da Paz3, E. Pedra
biopsies but in 5/11 biopsies score was upgraded to PRGS 2. In the "PAS Dias1
1
confirmed PRGS1" group an additional BerEp4-staining confirmed in 65/ Federal Fluminense University, Brazil, 2 Alcides Carneiro University
74 the PRGS 1 and lead to an upgrading of the score to PRGS 2 in 9/74 Hospital of the Federal University of Campina Grande, Brazil,
3
biopsies. University Hospital Lauro Wanderley/EBSERH/UFPB, Brazil
After HE staining, 50/339 biopsies (15%) were classified as “uncertain”.
After additional PAS staining, 26/50 biopsies were classified PRGS 1, 18/ Background & Objectives: The tumour stroma plays an important role
50 biopsies classified PRGS 2 and 6/50 “remaining uncertain”. After in the initiation and progression of neoplasia, rich stroma in a tumour
further BerEp4 staining, 1/6 biopsies were classified PRGS1 and 5/6 tissue can promote tumour invasion and aggressiveness. Tumour-stroma
PRGS 2. In the group of 26/50 PRGS1 further BerEP4-staining lead in ratio (TSR) is a histological feature, reflecting the value of the stromal
3/26 to an upgrading of the score to PRGS 2 and confirmed in 23/26 component that surrounds cancer cells. In different studies, the TRS
biopsies the PRGS 1. stands out as a potential prognostic factor. Outline the clinicopathological
Conclusion: In this cohort of patient with PM of gastric origin, additional profile of patients diagnosed with colorectal cancer and evaluate the in-
staining with PAS and/or BerEp4 showed residual tumour cells in 15/95 terobserver agreement in the estimation of TRS.
(15.8%) biopsies initially classified PRGS1. The number of “uncertain” Methods: Colorectal adenocarcinoma fragments, paraffin-embed-
biopsies could be reduced from 50 to zero and residual tumour cells were ded, from patients of the Napoleão Laureano Hospital Paraíba,
shown in 23 of these 50 biopsies (46%). Supplementray stainings showed Brazil, between 2017-2018.Excluded patients with neoadjuvant
the presence of residual tumour cells not only in uncertain cases but also treatment. The analysed variables were: age; sex;
in formerly (HE-based) tumour-free classified biopsies. anatomopathological features and TSR.TSR was determined based
on histological sections stained, routine HE, on the T-status deter-
mining slide. TSR were separated into two categories: stromal per-
PS-20-061 centage ≤ 50%-stromal poor; stromal percentage> 50%-rich in stro-
Tumour microenvironment: tumour-stroma ratio and cancer- ma. The interobserver concordance in the estimation of the TSR
associated fibroblasts was observed among three pathologists: two pathologists with
R.M. Souza da Silva1, E. Pedra Dias1 more than 10 years of professional experience and one trained
1
Federal Fluminense University, Brazil pathologist (e-learning training in TSR determination), with less
than 5 years.
Background & Objectives: Current research focuses on the study of Results: Ninety-eight patients participated in this study, 54.1% male, with
tumour microenvironment, especially the stroma. Fibroblasts, which are a mean age of 61.9 years. The left colon was the most common topogra-
the major components of cancer stroma, are called cancer-associated fi- phy (75.5%). Perineural invasion was frequent in 40.8%, angiolymphatic
broblasts (CAFs) and are similar in morphology to myofibroblasts. CAFs in 31.6% and lymph node metastasis in 40.8%. The T3 status was found
are fundamental regulators of tumour progression (tumour-stroma in 75.5% of the patients. The concordance between the TSR percentages
crosstalk and cancer cell migration) and influence response to therapeutic of the three pathologists was almost perfect (ICC above 0,8). There was
treatments. To describe the clinical profile of patients with colorectal greater agreement among pathologists in the estimation of stromal-poor
adenocarcinoma (CRA), determine the tumour-stroma ratio (TSR), deter- tumours.
mine the presence of CAFs and investigate associations between these Conclusion: The TSR estimate is simple, based on routine histological
variables. material, without the need for additional special techniques or extra costs,
Methods: Retrospective study, paraffin-embedded CRA fragments from easy to detect and has high agreement among pathologists.
patients at the Lauro Wanderley University Hospital, Paraíba, Brazil.
Excluded patients with neoadjuvant treatment. Variables analysed: age;
sex; anatomopathological variables, TSR and the presence of CAFs. The PS-20-063
TSR determined based on histological sections, on the T-status determin- Quantitative morphometry of colorectal cancer vascularity
ing slide. TSR were separated into two categories: stromal poor - TSR ≤ A. Stanek-Widera1, M. Biskup-Frużyńska1, J. Młynarczyk-Liszka1, R.
50%; rich in stromal – TSR > 50%. CAFs were defined as stromal spindle Lamch1, D. Lange1
cells with cytoplasmic immunostaining for α-SMA (high expression de- 1
Tumour Pathology Department, Maria Sklodowska-Curie Memorial
fined as positive immunostaining > 10% of cells), observed in the esti- Cancer Center and Institute of Oncology, Gliwice Branch, Poland
mated area of TSR, in the tumour front and around tumour cells.
Results: Thirty-five patients participated in this study, 60.0% male, mean Background & Objectives: Multifactor morphometric evaluation of vas-
age of 58.94 years. The T3 status was found in 71.4% of patients.A cular network in colorectal cancer primary tumour to identify and assess
stromal-rich tumour was observed in 54.3% of the cases. Well differenti- prognostic factors and markers of metastatic potential in untreated patients.
ated tumours presented the lowest stromal proportion(p=0.048). Stromal- Methods: Samples of tumours from 80 cases of untreated colorectal
rich tumours was observed when perineural invasion occurred(p=0.023), cancer in stage pT1-pT4 were used as material for immunohistochemical
angiolymphatic invasion(p=0.019) and tumour budding (p=0.008). assays. Morphometric parameters of vessels (density, average surface
Fibroblasts with high expression of α-SMA were identified in all cases, area, perimeter, elongation ratio, compactness and fullness) were estimat-
therefore CAFs, with high frequency for all the topographies observed ed by Factor VIII and Podoplanin stains in tumours with metastases
(ranging from 88.2%-97.1%). versus those without metastases. Vessels characteristics assessed using
Conclusion: The TSR is associated with prognostic factors of aggres- Factor VIII staining were compared with Podoplanin estimates and cor-
siveness, showing a strong and independent prognostic parameter. CAFs related with T and N stage.
Virchows Arch

Results: The study shows that average density of lymphatic vessels in a long-term follow-up. Patients were divided in a discovery and valida-
colorectal carcinoma is substantially higher in cases with nodal metasta- tion set. In addition to NDBE samples, HGD/EAC samples of 9 patients
ses and suggests that the intensity of lymphangiogenesis in colorectal in the discovery set were studied as well. Both high throughput miR-
cancer can be considered a negative prognostic factor. The examined profiling (Taqman Low Density MicroArray cards; TLDA) and individ-
vessel shape factors showed statistically significant differences between ual assays were used.
study groups. It may reflect deformation of lymphatic vessels in cases Results: The discovery set revealed eleven upregulated miRs in NDBE
with metastasis. Also, it indicates the possibility of using the discussed tissues from cases compared to controls. Thirteen miRs showed higher
morphometric features as prognostic factors. expression levels in HGD/EAC versus NDBE samples from controls. Of
Conclusion: Present study shows that Podoplanin assay provides more these, three were similarly upregulated in NDBE and HGD/EAC from
precise and significant estimates of vascular morphometric parameters cases compared to NDBE samples from controls (i.e., miR-18a, 93, 331-
than Factor VIII and therefore is recommended for further studies. 5p), potentially serving as informative biomarkers for high progression
Tumour vascularity characteristics of colorectal cancer might be used as risk. No significant differences were found between paired NDBE and
prognostic factors in combined treatment strategy planning and in treat- HGD/EAC samples. However, these results were not confirmed in the
ment outcomes. Studies in this field are in progress. validation set.
Conclusion: Early identification of BE patients at risk for progression
remains challenging. This study shows that NDBE samples of
PS-20-064 progressors and non-progressors do not differ in the expression of miRs.
Morphological features of acute appendicitis in elderly patients
I. Strumfa1,2, S. Lapsa1, R. Uljanovs1, I. Fridrihsone1,2, A. Ozolins1, J. Erasmus MC fellowship appointed to Dr. K. Biermann. Funders had no role
Gardovskis1 in study design, data collection, analysis and preparation of the manuscript.
1
Riga Stradins University, Latvia, 2 Department of Pathology, Latvia

Background & Objectives: Acute appendicitis in the elderly population PS-20-066

is less frequent than in young patients but can follow a more severe PDL-1 expression in colorectal cancer is associated with microsatel-
course. The aim of our study was to compare the morphology of appen- lite instability
dicitis and background changes in elderly versus young patients under- P. Tziakou1, T. Marinis2, E. Arkoumani1, A. Zizi-Sermpetzoglou1
1
going appendectomy. Department of Pathology of Tzaneio General Hospital of Piraeus,
Methods: Consecutive, retrospective cases of surgically treated acute ap- Greece, 2 1st Department of Surgery of Tzaneio General Hospital of
pendicitis were identified. Two cohorts were defined by age: young (18-35 Piraeus, Greece
years) versus elderly (>65 years) patients. Tissues were evaluated for pres-
ence and stage of appendicitis (early versus phlegmonous versus gangre- Background & Objectives: PD-L1 expression on tumour cells may be
nous); occurrence of perforation; presence and type (eccentric versus con- induced by the immune microenvironment, resulting in immune escape
centric) of chronic vascular stenosis in a.appendicularis, small mesenteriolar and an adverse prognosis in many malignancies. The role of PD-L1
and submucosal arteries and arterioles; any combined pathologies. expression in colorectal carcinoma is less clear, with some published
Results: Archive search yielded 59 elderly and 97 young patients sub- studies reporting conflicting results as to whether PD-L1 expression in-
jected to appendectomy for suspected acute appendicitis. Elderly patients dicates a better or worse prognosis.
were characterised by significantly more frequent gangrenous appendici- Methods: We investigated immunohistochemical expression of PD-L1 in
tis (p<0.0001) and perforation (p<0.0001). Chronic vascular stenosis was 95 paraffin-embedded colorectal carcinoma tisuue samples with known
more frequent in elderly cases (69.8% [95% confidence interval 56.4- microsatellite instability and its correlation with clinicopathologic param-
80.6] versus 17.1% [9.9-27.8] of young patients; p<0.0001); in these eters and survival.
patients it showed concentric pattern contrasting with focal eccentric ste- Results: The 19 (18%) CC specimens displayed a positive membranous
nosis in the young (p < 0.0001). In addition, appendicitis in elderly pa- staining reaction for PD-L1, while 81 (72%) had a negative staining. PD-
tients was characterised by more frequent co-occurrence of apical diver- L1 expression on tumour cells was evaluated using a three-tiered grading
ticula (p=0.0383) and tumours (p < 0.0001), mainly serrated adenomas. system: 0=<5% of the tumour cells; 1=5-49% of tumour cells; and
Conclusion: Morphologically, acute appendicitis in elderly patients is 2=≥50% of tumour cells with membranous staining of any intensity.
more severe and frequently accompanied by significant background PD-L1 expression was only seen in resections of the primary tumour
changes that can have pathogenetic significance and underline the role (P=0.010), mostly in cases without neoadjuvant therapy. Histologically,
of surgical treatment. the PD-L1 positive tumours were more likely to be poorly differentiated
(P<0.001) with a medullary phenotype. Angiolymphatic and perineural
invasion had no bearing on PD-L1 expression. In the cases without neo-
PS-20-065 adjuvant therapy, the 3-year disease- specific survival rate for the PD-L1
Histology-based microRNA profiles do not predict Barrett's oesoph- positive (n=13) and negative (n=47) groups were 73% and 68% respec-
agus progression to oesophageal adenocarcinoma tively (P=0.1786). Interestingly, among the microsatellite-instability-
L. Suzuki1, A. Gillis1, L. Dorssers1, J. Henriquez1, A. Koch1, M. Bruno1, positive patients, PD-L1 expression was associated with reduced
M. Spaander1, L. Looijenga1, K. Biermann1 disease-specific survival.
1
Erasmus MC, The Netherlands Conclusion: PD-L1 may serve as a useful molecular marker because it is
considered as poor prognostic factor for survival. Furthermore, it may be
Background & Objectives: This study aims to identify and validate useful in prognostic stratification of high microsatellite-instability colo-
microRNAs (miRs) that are differentially expressed in non-dysplastic rectal carcinoma.
Barrett’s oesophagus (NDBE) samples from progressors compared to non-
progressors as potential prognostic biomarkers to identify BE patients at risk
for oesophageal adenocarcinoma (EAC), prior to histological changes. PS-20-067
Methods: BE samples of patients from a Dutch multicenter prospective Impact of tumour budding in gastric carcinoma
cohort study (PROBAR) were investigated (n=34). NDBE of 16 patients D. Ulase1, S. Heckl2, H. Behrens3, S. Krüger3, I. Strumfa4,5, C. Röcken3
1
who developed high grade dysplasia (HGD) and/or EAC (cases) was Department of Pathology, Riga Stradins University, Latvia,
2
compared to NDBE of 18 patients that did not progress (controls) after Department of Internal Medicine I, University Hospital Schleswig-
 Virchows Arch

Holstein, Kiel, Germany, 3 Department of Pathology, Christian- error caused by variation in field size of different microscope
Albrechts-University, Kiel, Germany, 4 Riga Stradins University, brands. Occupied area>10% in any biopsy favoured ITB and was
Latvia, 5 Department of Pathology, Latvia statistically significant.
Conclusion: Differentiating ITB and CD is possible on biopsy,
Background & Objectives: Gastric carcinoma (GC) is a heteroge- especially on mapping. As caseation is not always seen in TB,
neous disease with high mortality and variable histological features other features need careful observation. Submucosal granulomas
and genotypes. Presence of distant metastases, the depth of invasion otherwise described in CD can also be seen in ITB while discon-
and lymph node involvement have traditionally been recognized as tinuous inflammation, hyalinization and epithelial regeneration can
important factors predicting outcome. Tumour budding (TB) has be features of CD too. We also recommend use of a new param-
been shown to be predictive of lymph node metastasis, lymphatic eter for better differentiation.
and venous invasion, distant metastasis, and local recurrence in var-
ious cancers. However, its significance in GC is unclear yet.
Therefore, the study aim was to assess TB and correlate it with clin- PS-20-069
icopathological parameters in GC. Cardiac-type epithelium development after ooesophagectomy: as-
Methods: TB was evaluated (according to ITBCC 2016 recommenda- sessment of its origin and implications
tions) in the invasive front of the tumour using the hotspot method, D. Vinha Pereira1, J. Castela2, S. Mão de Ferro3, R. Fonseca4, A. Dias
counted at 200x magnification per 0.785 mm2 field and scored as Bd0 Pereira3, P. Chaves4,5
1
(no buds), Bd1 (1-4 buds), Bd2 (5-9 buds) or Bd3 (≥10 buds). Cases with Pathology Department, Instituteo Português de Oncologia de Lisboa
TB present were divided into low-budding (Bd1/Bd2) and high-budding Francisco Gentil, Lisbon, Portugal, 2 Gastroenterology Department,
(Bd3) groups, and associations between TB score and clinicopathological Instituteo Português de Oncologia de Lisboa Francisco Gentil E.P.E.,
parameters were analysed by Kendall‘s tau test. Lisbon, Portugal, 3 Gastroenterology Department, Instituteo Português
Results: Among 456 consecutive, surgically treated GCs, 115 (25.2%) de Oncologia de Lisboa Francisco Gentil E.P.E., Lisbon, Portugal,
had no TB, 104 (22.8%) had low TB, and 237 (52.0%) – high TB. A 4
Pathology Department, Instituteo Português de Oncologia de Lisboa
statistically significant association was observed between TB score and Francisco Gentil E.P.E., Lisbon, Portugal, 5 Faculdade de Ciências da
pT (p<0.001), pN (p<0.001) and M categories (p<0.001), tumour grade Saúde da Universidade da Beira Interior, Covilhã, Portugal
(p<0.001), lymphatic invasion (p<0.001), perineural invasion (p<0.001), Background & Objectives: The congenital versus metaplastic origin of
but not venous invasion (p=0.119). cardiac epithelium (CE) is under debate. Gastrooesophageal anastomosis
Conclusion: In GC, higher tumour budding is significantly associated seems ideal to study the development of CE, reproducing its natural
with higher invasion depth, lymph node metastasis, distant metastasis, history. Our aim was to evaluate the prevalence of CE at different time-
higher grade, lymphatic and perineural invasion. Thus, the presence and points post-oesophagectomy.
extent of tumour buds could be a useful predictive marker in GC. Methods: We developed a prospective study of patients who undergone
oesophagectomy with gastric pull-up in our Institution during one year.
Upper gastrointestinal endoscopy was performed 3 and 15 months after
PS-20-068 surgery; anastomosis was evaluated with white-light, Narrow band
A prospective analysis of endoscopic colonic biopsies to differentiate Imaging and Near Focus; targeted biopsies from mucosa different from
intestinal tuberculosis and Crohn's Disease on histology squamous-oesophageal or gastric-corpus mucosa (non-native mucosa -
J. Varshney1, R. Chaturvedi1, A. Joshi1, D. Gupta2 NNM) and protocoled biopsies from oesophagus, stomach and anasto-
1
Department of Pathology, Seth GS Medical College and King Edward mosis were performed. Histology was evaluated by GI pathologists.
Memorial Hospital, Mumbai, India, 2 Department of Gastroenterology, Results: 19 patients were included and 15 were eligible for the 15th
Seth GS Medical College and King Edward Memorial Hospital, Mumbai month endoscopy. NNM was identified in 17/19(89,5%) at 3 months,
400012, India and in all patients (15/15) at 15 months. CE was histologically confirmed
in all NNM areas in both time-points, but also in 33% of endoscopically
Background & Objectives: Crohn’s disease (CD) and intestinal tuber- non-recognized areas - NNM has a sensitivity, specificity, positive and
culosis (ITB) are chronic granulomatous diseases of the intestine with negative predictive value for CE’s diagnosis of 84%, 100%, 100% and
overlapping clinico-pathological features. Differentiating the two poses 67%, respectively. Intestinal metaplasia was identified in 2/19 patients
a dilemma to the clinicians as well as the pathologists. The limited tissue (10,5%), at 3 months.
available in biopsies makes it even more challenging. But this is essential There was a significant increase of NNM length between the first and
for appropriate management as misdiagnoses can cause flare up or de- second endoscopic evaluation (p=0,011). The presence of endoscopic
layed appropriate treatment. Due to limited literature available on this, we oesophagitis was statistically associated with increased CE extension
conducted a study aimed at analysing their differentiating histological (p=0,016).
features along with clinical correlation. Conclusion: CE development after oesophagectomy is an almost univer-
Methods: This was an eighteen months prospective study of 50 sal and extremely rapid metaplastic reflux-induced phenomenon, with
clinically suspected ITB or CD cases. Endoscopic colonic biopsies good endoscopic-histological correlation. The congenital nature of CE
(2-5 per patient) were taken and cases re-grouped as ITB and CD, should be re-evaluated.
based on minimum 6 months follow-up with Anti Tuberculosis
Treatment (ATT) response and/or culture. Histological features
(size, number, location of granulomas, giant cells, hyalinization, PS-20-070
follicular hyperplasia, pyloric metaplasia, epithelial regeneration Mucin 16 expression in colorectal carcinomas: a predictor for peri-
etc.) were studied and clinically correlated. toneal dissemination?
Results: Large (>400 microns) confluent granulomas, suppuration/ B. Yeni1, U.O. Idiz2, E. Yarikkaya3, M. Cin4, H. Dincer3, G. Usul3, N.
caseation, giant cells and deep ulcers favoured ITB while small Dursun4
1
discrete granulomas, mucosal fibrosis, chronic and discontinuous University of Health Sciences, Department of Pathology, Turkey,
inflammation favoured CD on histology. A new parameter- ‘biopsy 2
Istanbul Training and Research Hospital, General Surgery, Turkey,
3
area occupied by granulomas’ was introduced which alone covers Istanbul Training and Research Hospital, Pathology, Turkey,
4
two variables (used in previous studies), i.e. size as-well-as number University of Health Sciences, Istanbul Health Practice and Research
of granulomas/low-power-field, with an advantage of nullifying the Hospital, Department of Pathology, Turkey
Virchows Arch

Background & Objectives: Colorectal carcinoma(CRC) is one of the 500, MANEC= 33 cases). Since they are frequently aggressive lesions,
most frequent cancer in men and women. Pathologic tumour stage is the collections and characterization of these neoplasms could help in
the strongest prognostic factor in patients with CRC. The presence better defining prognosis and treatment.
of peritoneal carcinomatosis (PC) is critical and can change the
stage of disease. Carbohydrate antigen 125(CA125) also known as
Mucin 16(MUC16) is a glycoprotein found on tumour cells that PS-21-002
reacts with mesothelial cells. HIV hepatic biopsy, what else?
Although there are plenty of studies investigating CA125 expression D. Argyropoulou1, T. Robalo Nunes2, S. Boavida2, H. Oliveira Coelho1,
in ovarian carcinoma and in some degree gastric adenocarcinoma, M. Brito1
1
there is insufficient data for CRC. We aimed to investigate MUC16 Department of Pathology, Hospital Garcia de Orta, Portugal,
2
expressions in colorectal tumours in our series and crosscheck the Department of Infectiology, Hospital Garcia de Orta, Portugal
results with patients’ prognostic factors, especially PC.
Methods: Total of 30 patients’ HE stained slides (13 PC positive, 17 PC Background & Objectives: The purpose of this work is to report a
negative) diagnosed with CRC were retrieved from our archive and re- case of a 56-year-old female HIV positive patient, with the diagnosis
examined. We applied immunohistochemistry (MUC16) to both groups’ of amyloidosis performed at the liver biopsy. Amyloid is defined as
tumours and PC positive omentums. an amorphous, eosinophilic proteinaceous tissue deposit, with typical
Results: In our PC positive group, five cases had both positivities in green birefringence in polarized light after Congo red staining. There
tumour and peritoneum (5/13). Only two cases showed positivity in are over 25 different proteins acknowledged and can affect any organ
peritoneum but no reaction in tumour (2/13). None of our PC positive and tissue. Their enigmatic clinical presentation ranges from clinical-
cases were positive with MUC16 in tumour together with negativity ly insignificant to life-threatening.
in peritoneum. In PC negative group, six cases showed positive stain- Methods: The patient was a retired seamstress, with background of
ing with MUC16 (6/17). These six cases had adverse prognostic chronic osteomyelitis under antibiotic therapy, fistulizing perianal
factors like; distant metastasis, high histologic grade, circumferential disease, HIV positive under medical treatment that was admitted in
tumour, lymphovascular and perineural invasion. In 13 MUC16 pos- the Emergency with fever, abdominal pain and nausea followed by
itive cases, nine had either lymphovascular or perineural invasion diarrhoea and haematochezia. She presented weight loss of 7kg in a
(9/13) and nine had lymph node metastasis (9/13). pT1 and pT2 month. The physical examination showed hepatosplenomegaly. The
tumours showed no reaction with MUC16. blood analyses revealed microcytic anemia, leucocytosis,
Conclusion:MUC16(CA125) may predict PC in CRC and can be used as neutrophilia, high inflammatory markers and a high alkaline phos-
a prognostic tool. Using such marker while diagnosing the patient may phatase. TC-scan revealed a small nodular single hepatic lesion and a
change the therapy options and result in a better survey. liver biopsy was performed.
Results: The liver biopsy revealed a perivascular and peri-sinusoidal
deposition of an amorphous, hyaline substance that stained positive with
Wednesday, 11 September 2019, 09:30 - 10:30, Agora 3 Congo red and showed green birefringence in polarized light. The diag-
PS-21 | Digestive Diseases Pathology – Liver / Pancreas nosis of amyloidosis was given. There are 26 patients with amyloidosis in
our hospital; this was the first in a liver biopsy.
Conclusion: The diagnosis of amyloidosis at liver biopsy is rare. This
PS-21-001 diagnosis was crucial for the adequate patient management. In our
Pure and mixed gallbladder neuroendocrine neoplasms: rare and Institution there are documented, in the past 10 years, 3 cases of
orphan lesions amyloidosis secondary to a chronic inflammation state due to HIV
N. Ahmed1, F. Pedica2, F. Falcinelli1, F. Sanvito2, I. Sassi2, C. Doglioni2,1 infection.
1
Vita-Salute San Raffaele University, Milan, Italy, 2 Pathology Unit,
Division of Experimental Oncology, IRCCS San Raffaele Scientific
Institute, Milan, Italy PS-21-003
Grading neuroendocrine neoplasms of the pancreas according to the
Background & Objectives: Neuroendocrine differentiation in the new 2017 World Health Organization grading system: a retrospec-
neoplasms of the gallbladder are rare since they represent around tive study of 18 cases
0,5% of all gallbladder cancers. Mixed adeno-neuroendocrine carci- S. Ben Khalifa 1 , N. Abdessaied 1 , T. Zahmoul 2 , S. Chaeib 2 , O.
nomas (MANEC) are combined neoplasms in which both compo- Belkacem2, A. Ben Abdelkader1, M. Mokni1
nents represent at least 30% of the tumour. In the last 2 years we 1
Pathology Department of Fattouma Bourguiba Hospital, Monastir,
found 2 MANEC of the gallbladder, so we retrospectively investigat- Tunisia, 2 Department of Pathology; Farhat Hached Hospital; Sousse,
ed our Archive to define their frequency in our Hospital and estimate Tunisia
the incidence of the disease.
Methods: We searched for gallbladder “MANEC” in our database from Background & Objectives: Pancreatic neuroendocrine neoplasms
January 2009 to March 2019, and then we defined how many gallblad- (PanNENs) are a rare and heterogeneous disease comprising only 2%
ders were neoplastic in these last 10 years. of all pancreatic neoplasms, but have increased significantly in incidence
Results: Of the 8087 sampled gallbladders, 200 were neoplastic (2,4%). over the past few decades. The aim of the current study is to review
In particular, 4 of them were diagnosed as MANEC (0,05%), the others updated grading system of the pancreatic NEN.
were dysplastic (1% low-moderate grade, 0,4% high grade), adenocarci- Methods: We retrospectively analysed the clinical and pathologic data of
nomas (1,4%) and a pure moderately differentiated NEC (0,012%). 18 patients diagnosed at our Institution from 2010 to 2018. Age, Sex ratio
All MANECs displayed a poorly differentiated adenocarcinoma plus a and tumour size were recorded. All slides for each case were reviewed.
neuroendocrine carcinoma with Ki67 higher than 30%. Two cases pre- Tumours were graded according to the number of mitoses and/or Ki-67
sented well distinct counterparts with numerous Paneth cells CDX-2+ in index, using the 2017 WHO Classification.
the neuroendocrine population, whilst in the other cases the two popula- Results: There were 12 men and 6 women with a mean age of 59 years
tions were deeply intermingled. (34-80 years). The average tumour size was 8 cm (2 to 18 cm). PanNENs
Conclusion: The neuroendocrine neoplasms of the gallbladder are very were well-differentiated in 83,3% (n=15) with 40% of PanNET G1 (n=6),
rare and only a few reports are found in the literature (pure NEC = around 53,3% of PanNET G2 (n=8) and % 6,6 of PanNET G3 (n=1). Poorly-
 Virchows Arch

differentiated PanNEM (PanNE carcinomas) represented 16,6 % of cases more effective therapies are required for. Modulated electro-hyperthermia
(n=3). (mEHT) is a non-invasive therapy which can generate selective heat
Conclusion: The WHO classification released in 2010 led to a significant (≤42°C) in cancer based on its elevated glycolysis, ion concentration
change in the grading system of NENs of the digestive system. However, and permittivity.
there are a number of remaining issues. In the revised version of the Methods: Panc1 pancreas adenocarcinoma cells were treated in vitro
“WHO Classification of Tumours of Endocrine Organs” published in using mEHT for 60 min; 10 μM/ml gemcitabine for 24 h (G); irradiation
2017, to solve the problems of high-grade (grade 3) neuroendocrine neo- using 2Gy for 2.5 min (137Cs, R); and with combinations of mEHT and
plasms, they are divided into PanNET G3 and neuroendocrine carcino- G (mEHT+G) or R (mEHT+R). Samples were tested 24 h post-treatment
mas, grade 3 (PanNEC G3) depending on their histo-morphologic char- for cell stress, DNA double-strand brakes, tumour viability, apoptosis and
acteristics. The PanNEC G3 category is associated with a better prognosis ALDH1+ progenitor/stem cells.
and does not significantly responds to cisplatin-based chemotherapy. Results: mEHT treatment alone resulted insignificant tumour cell apo-
ptosis detected by morphology and flow cytometry, which was more
pronounced after combined therapies (mEHT+G and mEHT+R).
PS-21-004 Immunocytochemistry revealed significant upregulation of γH2AX and
SOX9, a highly sensitive and specific marker to discriminate hepato- cleaved/activated caspase-3 positive cell fractions, while pAKT and the
cellular carcinoma from intrahepatic cholangiocarcinoma ALDH1+ cells were reduced in the mEHT, G, mEHT+G, mEHT+R
X. Ding1, B. Trac1, X. Duan1 groups, compared to controls. In contrast, irradiation alone did not signif-
1
Loyola University Medical Center, USA icantly affect tumour cell viability and apoptosis.
Conclusion: mEHT treatment alone can induce cell stress, DNA double-
Background & Objectives: Hepatocellular carcinoma (HCC) and strand breaks and apoptosis in pancreas adenocarcinoma cells. Combined
Intrahepatic cholangiocarcinoma (ICC) are two most common primary with radiotherapy, it can reduce pAKT and tumour stem cell ratio in Panc1
liver cancers. The differential diagnosis between these 2 entities is rela- cell cultures, thus improves the efficacy of radiotherapy. Combined with
tively straightforward if the tumour exhibits typical histological features. gemcitabibne mEHT is as efficient as chemotherapy, and can induce also cell
However, a differential diagnosis between ICCs and HCCs could be stress and apoptosis which leads to tumour destruction.
challenging, particularly in cases of poorly differentiated carcinoma.
Immunohistochemical markers that are commonly used in current clinical This study was funded by a grant of the National Research and Innovation
practice include arginase-1, HepPar-1, glypican-3, and CK19. However, Office (NKFIH-NVKP_16-1-2016-0042) and by the EFOP-3.6.3-
none of these are sensitive enough to distinguish high grade HCC from VEKOP-16-2017-00009 project.
poorly differentiated cholangiocarcinoma. Sex-determining Region Y
box 9 (SOX9) has been shown to be a tumour stem cell marker as well
as be dysregulated in certain cancer. In this study, we examined the ex- PS-21-006
pression of SOX9 in HCCs, CCs and combined HCC and Liver adenomatosis and NAFLD developed in the context of hered-
cholangiocarcinoma. itary fructose intolerance: a case report
Methods: We herein examined the immunohistochemical expression of L. Ghannem1, A. Beaufrère2,3, A. Montasser4,5, F. Cauchy6, G. Couchy7,
SOX9 in HCCs (n=20), ICCs (n=18), combined HCC and cholangiocar- J. Zucman-Rossi7, O. Soubrane6, V. Paradis2,3
1
cinoma (n=7) in surgical resection specimen. A nuclear staining of SOX9 Pathology Department, Beaujon University Hospital, AP-HP, Clichy,
was treated as positive and was scored for intensity (weak, moderate and France, 2 Pathology Department, Beaujon University Hospital, AP-HP,
strong staining). Cytoplasmic staining was considered nonspecific. Clichy, France, 3 INSERM U1149, Beaujon University Hospital, Clichy,
Fisher’s exact test with two tails was performed using the GraphPad France, 4 Pathology Department, Beaujon University Hospital, AP-HP,
statistical software. Clichy, France, 5 Pathology Department, Theodor Bilharz Research
Results: Benign hepatic bile duct epithelium exhibits diffuse moderate to Institute, Giza, Egypt, 6 Department of HPB and Pancreatic Surgery,
strong SOX9 nuclear staining while benign hepatocytes are completely Beaujon University Hospital, AP-HP, Clichy, France, 7 INSERM, UMR
negative for SOX9 expression. 20 HCC cases tested are all negative for 1162, Gènomique Fonctionnelle des Tumeurs Solides, Institute
SOX9 expression. 7 of 18 CC cases show diffuse strong nuclear staining Universitaire d’Hèmatologie, Paris, France
of SOX-9 while 11 of 18 CC cases exhibit diffuse moderate SOX-9
nuclear expression. For combined HCC and cholangiocarcinoma cases Background & Objectives: Hereditary fructose intolerance (HFI) is
tested, the cholangiocarcinoma component is diffusely positive for SOX- an autosomal recessive metabolic disorder resulting from a defi-
9 while the HCC component is completely negative. ciency in fructose-1-phosphate aldolase activity. This deficiency
Conclusion: SOX-9 is a highly specific and sensitive marker to distin- induces postprandial hypoglycemia after fructose ingestion.
guish cholangiocarcinoma from hepatocellular carcinoma. Positive SOX- Association between HFI and non-alcoholic fatty liver disease
9 staining could be used to exclude hepatocellular carcinoma. Further (NAFLD) has rarely been described. The aim of this study was
study will be conducted to elucidate SOX-9 expression in different he- to report an observation of NAFLD and hepatic adenomatosis
patic metastatic tumours from other organs. genotypically typed developed in the context of HFI.
Methods: We report the case of a 35-year-old female with HFI, referred
to our hospital after the discovery of twelve hepatic nodules in both lobes.
PS-21-005 The patient had no history of diabete or obesity. A right hepatectomy was
Mechanism of action of modulated electro-hyperthermia in resolving realized. The surgical specimen was fixed in 10% neutral buffered for-
radio-resistance of pancreas adenocarcinoma and improving malin and was adequately sampled. Paraffin sections from tumours and
gemcitabine efficacy non-tumoural liver were histologically examined. Liver tumours were
G. Forika1, T. Vancsik1, A. Balogh2, Z. Benyó2, T. Krenács1 phenotypically (immunohistochemistry) and genotypically typed
1
1st Department of Pathology and Experimental Cancer Research, (Targeted next generation sequencing).
Semmelweis University, Hungary, Hungary, 2 Semmelweis University, Results: Macroscopically, three tumours were observed, well-limited and
Institute of Clinical Experimental Research, Budapest, Hungary, Hungary red-brownish. Microscopically, all lesions corresponded to hepatocellular
adenoma and the non neoplasic liver displayed moderate macrovacuolar
Background & Objectives: Pancreatic adenocarcinomas are among the steatosis without features of steatohepatitis. Immunohistochemical anal-
worst to respond to oncotherapy with 5-year survival rate under 10% thus ysis showed an overexpression of C-reactive protein and serum amyloid-
Virchows Arch

associated antibodies in tumours. L-FABP and β-catenin antibodies were Methods: 173 patients underwent DPC between 1994 and 2017 at our
normally expressed in tumour cells and glutamine synthetase staining was Institutsion: 59 AC (from 1994 to 2008) and 114 with MAA (2008 on-
negative. Molecular analysis confirmed the diagnosis of inflammatory wards). MAA specimens were examined by the same two pathologists
hepatocellular adenoma with gp130 mutation. and a standarized pathological protocol was applied, whereas previous
Conclusion: We report here a case of liver adenomatosis associated with reports (AC) were randomly assigned to any staff member.
NAFLD developed in a patient with HFI, that may suggest a possible link Results: Both groups differ in T stanging, more advanced staging was
between these pathologies. Thus, a specific clinical and radiological observed in MAA approach (>T3 86%) versus CA (>T3 76,6%). The
follow-up should be advised in patients with HFI for screening NAFLD number of isolated lymph nodes was much higher in the modified ap-
and development of liver tumours. proach (23,9 MAA versus 7,95 CA) and consequently the lymph node
ratio (metastatic lymph nodes/total lymph nodes,LNR) was lower in the
AMS group (0,07 MAA versus 0,16 AC). Complete resection rate (R0)
PS-21-007 were 73,3% in CA and 67,5% in MAA. Specific survival rates were 24,4
Heterogeneous ALCAM expression in pancreatic ductal carcinoma months for AC group and 32,8 months in MAA patients.
S. Giusca1, I.D. Caruntu1, D. Ciobanu1, A. Rusu1 Conclusion: MAA allows isolating a greater number of lymph nodes and
1
"Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania obtaining a lower LNR, a good prognostic factor. But, we have not shown
a significative increase in global survival with this approach, probably
Background & Objectives: In pancreatic tumour pathology, the because more advanced stages have been selected in this group.
Activated Leucocyte Cell Adhesion Molecule (ALCAM) role as prog-
nostic factor is poorly investigated, with contradictory results. Within this
context, our study aims to analyse the ALCAM expression in pancreatic PS-21-009
ductal carcinoma and associated preneoplastic lesions. ARX expression and alternative lengthening of telomeres identify
Methods: 46 cases of pancreatic ductal carcinoma, 28 of them presenting insulinomas that develop liver metastasis
associated preneoplastic lesions, were immunohistochemically investi- W. Hackeng1, W. Schelhaas2, F. Morsink1, C. Heidsma2, S. van Eeden2,
gated. ALCAM expression was assessed at membranous and cytoplasmic M. Vriens1, G. Valk1, E. Nieveen van Dijkum2, J. Offerhaus1, K.
level, by using an immunoscore based on the percentage of positive Dreijerink1, L. Brosens1
1
tumour cells and the intensity of reaction. Relationship between University Medical Center Utrecht, The Netherlands, 2 Amsterdam
ALCAM expression and clinico-pathological characteristics was statisti- University Medical Center, The Netherlands
cally analysed.
Results: ALCAM expression was strongly membranous in all low-grade Background & Objectives: Liver metastases are the leading cause of
preneoplastic lesions, with progressive loss in high-grade ones; no cyto- death in patients with pancreatic neuroendocrine tumours (PanNETs).
plasmic staining was noted. In 40 of 46 cases of pancreatic ductal carci- PanNETs are called “functional” if symptomatic by excess hormone pro-
noma, ALCAM was expressed both at membranous and cytoplasmic duction; functional “insulinomas” rarely metastasize and are generally con-
level, with a heterogeneous distribution: 5 cases had moderate membra- sidered benign. The primary treatment of insulinomas is surgery; if success-
nous and low cytoplasmic expression; 20 cases registered low membra- ful and symptoms resolve, patients are discharged from hospital follow-up.
nous staining with moderate cytoplasmic expression; 5 cases showed low Nevertheless, some insulinomas do give liver metastases. The value of
membranous and cytoplasmic staining; 10 cases displayed moderate prognostic markers to identify malignant sporadic insulinomas was inves-
membranous and cytoplasmic expression. In 6 cases, ALCAM immuno- tigated, since these patients might benefit from more extensive follow-up.
staining was completely absent. Statistical analysis revealed no signifi- Methods: Tissue-microarrays were constructed from 36 insulinomas. Data on
cant differences between membranous, respectively cytoplasmic functionality and clinical follow-up were collected. Expression of several re-
ALCAM expression, and clinico-pathological parameters defined for cently described prognostic markers and endocrine hormones and transcription
pancreatic ductal carcinoma (tumour extension, tumour grade, lymph factors (ATRX, DAXX, ARID1A, H3K36me3, Insulin, PDX1, Glucagon and
node metastasis, lympho-vascular invasion). ARX) was determined by immunohistochemistry. CDKN2A loss and the al-
Conclusion: From preneoplastic pancreatic lesions to tumour proliferation, ternative lengthening of telomeres phenotype (ALT) were determined by fluo-
ALCAM loses its membranous expression and gains a cytoplasmic one. The rescence in situ hybridization. Slides were scored blinded for follow-up.
low or absent membranous ALCAM expression does not seem to influence Results: Insulin, PDX1, glucagon and ARX were expressed in 100%,
an aggressive behaviour in pancreatic tumours, as in other malignancies. 100%, 61% and 11% (4/36) of insulinomas, respectively. No allelic
CDKN2A loss; or loss of ATRX, DAXX, or ARID1A expression were
observed. H3K36me3 was uniformly strong. 6% (2/36) showed ALT. 3
PS-21-008 patients developed liver metastasis after resection. All 3 metastatic
Comparison of two different approaches for pancreatoduodenectomy PanNETs showed ARX expression, and 2 also had the ALT phenotype.
by ductal adenocarcinoma of pancreas: pathological features Conclusion: ARX expression and ALT mark malignant behaviour of
M.L. Gomez Dorronsoro1, M. Mercado2, I. Fernandez de los Rios3, P. insulinomas. ALT has not been reported previously in insulinomas spe-
Sanchez Acedo4, I. Eguaras5, R. Beloqui6, I. Amat7 cifically. ARX expression which is normally absent in islet beta-cells
1
CHNavarra. Pamplona. Dpt. Pathology, Spain, 2 CHN.Pamplona. Dpt. suggests endocrine dedifferentiation. These markers might change the
Pathology, Spain, 3 CHN. Pamplona. Dpt.Pathology, Spain, standard of care in pancreatic insulinoma patients, but further validation
4
CHN.Pamplona. Dpt.Surgery, Spain, 5 CHN. Pamplona. Dpt. Surgery, is necessary.
Spain, 6 CHN.Pamplona. Dpt Pathology, Spain, 7 CHN. Pamplona Dpt.
Pathology, Spain
PS-21-010
Background & Objectives: To analyse the pathological differences re- Histomorphological and immunophenotypical subtypes of pancreat-
lated to survival between two types of surgical approach to cephalic ic ductal adenocarcinoma
duodenopancreatectomy (DPC) by ductal adenocarcinoma. Two types L. Haeberle1, L. Ingenhoff1, M. Schlensog1, S.A. Safi2 and I. Esposito1
1
of surgical approach are compared: classic approach (CA) and mesenteric Institute of Pathology, Heinrich Heine University and University
artery approach (MAA). The later includes CA and extends towards Hospital, Düsseldorf, Germany, 2 Department of General and Visceral
mesopancreas, a structure that extends from posterior face of pancreatic Surgery, Heinrich Heine University and University Hospital Düsseldorf,
head behind mesenteric artery and vein. Germany
 Virchows Arch

Background & Objectives: Prognostically relevant molecular sub- targeting of HER2 in PC may be alternate or complementary approach
types of pancreatic ductal adenocarcinoma (PDAC) can partly be to establish a precision medicine based on tumour characterisation.
recapitulated by immunohistochemistry. CK81 positivity and loss
of UTX expression seem to correlate with the more aggressive
“squamous” subtype, while HNF1A positivity is a suggested PS-21-012
marker for the less aggressive non-“squamous” PDAC. However, HER2 status of biliary tract cancer
the link between molecular/immunohistochemical subtypes and N. Hiraoka1, H. Yoshida1, H. Nitta2, A. Ohba1, C. Morizane1, T.
histomorphological subtypes is unclear. The aim of this study is Okusaka1
1
a detailed histomorphological and immunohistochemical analysis National Cancer Center Hospital, Tokyo, Japan, 2 Roche Tissue
of PDACs from a well-characterised cohort. Diagnostics, USA
Methods: Tumour samples of patients resected for PDAC (n=223) were
analysed regarding histomorphology and immunoprofile. A detailed Background & Objectives: Human epidermal growth factor receptor 2
histomorphological analysis of whole slides has been completed in 157 (HER2)-targeted therapy improves clinical outcomes in cases of HER2-
cases so far. Immunohistochemistry for HNF1A, CK81, UTX, p40 and positive breast and gastric cancers, although ineffective or recurrent cases
p53 was performed on tissue microarrays of all cases. HNF1A and CK81 also exist. One reason is assumed to be the heterogeneity of HER2 ex-
were assessed according to previously published criteria. For HNF1A and pression in cancer cells. Herein, we investigated HER2 amplification or
UTX, an immunoreactive score (IRS, 0-12) was (also) used. overexpression in biliary tract cancer (BTC), which is one of the most
Results: 124/157 (79%) conventional PDACs, 6/157 adenosquamous devastating cancers.
PDACs (3.8%) and 27/157 (17.2%) other histomorphological subtypes Methods: We examined HER2 protein expression using immunohis-
were found. CK81 or HNF1A positivity were not correlated with other tochemistry, HER2 gene amplification using fluorescence in situ hy-
immunohistochemical markers or classical prognostic features such as bridization, and both protein and transcript levels simultaneously
grading. Low UTX-IRS was correlated with poorer grading (p=0.002, using a gene–protein assay. These tests were performed using sam-
Mann-Whitney-U), but not with other markers. Neither CK81 nor ples from 459 cases of BTC surgically resected in National Cancer
HNF1A status correlated with survival in this cohort. Patients with Center Hospital, which included 110 intrahepatic
UTX-negative (IRS 0-1) PDACs showed significantly worse survival cholangiocarcinomas (ICCs), 187 extrahepatic cholangiocarcinomas
than patients with UTX-positive PDACs (p=0.0005, log rank). (ECCs), 80 gallbladder carcinomas (GBCs), and 82 ampullary carci-
Conclusion: Our preliminary results confirm that PDAC is a highly nomas (AVCs). HER2 status was assessed according to the guideline
heterogeneous entity both morphologically and regarding its for HER2 testing in gastrooesophageal adenocarcinoma.
immunoprofile. So far, there appears to be no clear relationship Results: HER2 positivity was found in 3.8% of ICC, 7.0% of ECC, 26.9%
between CK81-positive/UTX-negative ”squamous” subtype and of GBC, and 12.7% of AVC cases. More than 80% of these showed het-
histomorphological features. erogeneity of HER2 expression, and 70% of papillary adenocarcinomas
and 10% of non-papillary adenocarcinomas expressed HER2
homogenously. Reductions in HER2 expression were often found in deeper
PS-21-011 invasive areas with reductions in the differentiation status of cancer cells.
The evaluation of HER2 discordance and heterogeneity in pancreas There was sometimes a collision of two different types of cancer in HER2
adenocarcinoma expression.
S. Han1 Conclusion: These results suggest that a significant subgroup of HER2-
1
Department of Pathology, Dong-A University College of Medicine, positive BTC cases can be considered for HER2-targeted therapy.
Republic of Korea

Background & Objectives: HER2 (ERBB2) amplication and over- PS-21-013

expression are reported in 30-100% of pancreas carcinoma (PC). MET amplification was associated with adverse prognostic factors in
However, impacting treatment effects of trastuzumab for PC remain gallbladder cancers
largely undefined. In this study, we evaluated HER2 status associated Y. Kim1, S. Bang1, S. Jee1, S. Park2, S. Shin2, S.S. Paik1, K. Jang2
1
with gene copy number (GCN) gain and amplification and protein over- Department of Pathology, Hanyang University College of Medicine,
expression comparing the results of the tissue microarray (TMA) and the Seoul, Republic of Korea, 2 Department of Pathology, College of
matched whole tissue section (WTS), respectively. Medicine, Hanyang University, Seoul, Republic of Korea
Methods: Dual-colour siver-enhanced in sity dybridizaiton (SISH) and
immunohistochemistry (IHC) for HER2 were performed in TMA and the Background & Objectives: Mesenchymal epithelial transition (MET) is
paired WTS of 73 primary PC patients. The amplification status (GCN a proto-oncogene which encodes a heterodimeric transmembrane recep-
ratio>2), and GCN gain (average GCN>4) data were obtaind. The GCN tor tyrosine kinase for the hepatocyte growth factor. Aberrant MET sig-
variation and IHC results were evaluated by the 2018 CAP/ASCO guide- nalling has been described in a number of solid tumours, especially non-
lines for HER2 assessment. small cell lung cancer, and is associated with tumour progression and
Results: Among the 73 PC cases, HER2 IHC staining showed that 47 adverse prognosis. Since MET is a potential treatment target, knowledge
cases was negative, and 25 cases were equivocal and 1 case was positive of its prevalence and clinicopathological relevance is crucial.
in both TMA and the matched TWS, respectively. Amplification and Methods: We investigated MET expression and gene amplification
GCN gain of HER2 showed in 21.9% (16) and 23.3% (17) in TMA, i n 11 6 g a l l b l a d d e r c a n c e r s u s i n g t i s s u e m i c r o a r r a y.
and 15.1% (11) and 19.2% (14) in WTS, respectively. Analysing the Immunohistochemistry was used to evaluate c-MET overexpres-
patterns of HER2 protein and gene status, 16 patients showed HER2 sion, silver in situ hybridization to assess gene copy number.
discordance. HER2 heterogeneity was recognized in 38 cases (52.1%). Results: The prevalence of MET overexpression and amplification
Patients with HER2 discordance had significantly worse survival than was 27.6% and 10%. MET protein expression was not correlated
concordance (p<0.05). The group of HER2-Heterogeneity had signifi- with MET gene copy numbers. MET amplification was associated
cantly worse survival than the non-heterogeneous (p<0.05). with higher histologic grade (p = 0.029), advanced pT stage (p =
Conclusion: Through the evaluation of HER2 status, we identified the 0.026), lymph node metastasis (p = 0.008), AJCC stage (p =
importance of discordance and heterogeneity in PC. And in term of treat- 0.018), and perineural invasion (p = 0.018). MET overexpression
ment effects, even if the alteration of HER was minor portion, the was not associated with any clinicopathological parameters. No
Virchows Arch

survival difference was found according to the MET overexpres- 2009-2017, were retrospectively evaluated. We analysed the clinicopath-
sion and amplification status. ological parameters such patient’s age and gender and histopathological
Conclusion: Our data suggest that MET might be an interesting molecule parameters such grade of differentiation and pTNM stage, based on both
for targeted therapy in gallbladder cancer, because MET amplification 7th and 8th edition of AJCC Cancer Staging Manual. The overall survival
was found in a subset of tumour and associated with adverse prognostic rate was estimated after a period of follow-up ranging between 10 and 60
factors. MET amplification might be a more useful stratification biomark- months.
er than MET protein overexpression. Results: There were 36 HCCs included in the study. According to 7th
edition of AJCC, 20 cases were staged as pT2- and 16 HCCs were diag-
nosed in pT1 stage. After restaging, 10 pT2 cases were under-staged to
PS-21-014 pT1b. The 16 pT1-HCCs were re-staged as pT1a. We did not find a
Granulocytic Epithelial Lesion (GEL)-Positive Pancreatitis of correlation between overall survival rate and patient’s age (p=0.21) or
Heterotopic Pancreas grade of differentiation (p=0.55). Independently by the used staging sys-
S. Jun1, S.J. Kim2, G. Yoon3, S. Hong4,5 tem, the survival rate was not influenced by the pT stage (p=0.18 for 8th
1
Department of Pathology, Incheon St. Mary's Hospital, College of edition and p=0.92 for the 7th edition). The survival curve linearly de-
Medicine, The Catholic University of Korea, Republic of Korea, creased at 3 years after diagnosis, for both pT1 and pT2 cases.
2
Department of Pathology, Asan Medical Center, University of Ulsan Conclusion: Compared with the 7th edition of AJCC Staging System
College of Medicine, Republic of Korea, 3 Department of Pathology, book, in the 8th edition, there is a tendency of under-staging HCCs, which
Kyungpook National University School of Medicine, Republic of do not influence the overall survival rate. The prognostic impact of the 8th
Korea, 4 Department of Pathology, Asan Medical Center, Republic of edition changes should be estimated in a larger number of cases.
Korea, 5 University of Ulsan College of Medicine, Republic of Korea
This work was supported by a grant of the Romanian National Authority
Background & Objectives: Autoimmune pancreatitis (AIP) was formal- for Scientific Research, CNCS – UEFISCDI, project number 20
ly recognized based on the histologic features. Especially, type 2 AIP has PCCF/2018, code: PN-III-P4-ID-PCCF-2016-0006.
the definitive diagnostic feature, called granulocytic epithelial lesion
(GEL). GEL is characterised by periductal neutrophilic infiltration show-
ing clustered neutrophils underneath the ductal epithelium and within the PS-21-016
lumen. Clinically, type 2 AIP seems to be associated with inflammatory CAMTA-1 expression in 24 cases of hepatic epithelioid
bowel disease (IBD). hemangioendothelioma in a single Institute: diagnostic utility for dif-
Methods: We analysed clinicopathological features of GEL-positive pan- ferential diagnosis from hepatic angiosarcoma
creatitis among 165 resected heterotopic pancreas (HPs) [57 gastric H. Jung1, S. Ha1
1
(35%), 56 duodenal (34%), 30 omental (18%), and 22 jejunal (13%)]. Department of Pathology and Translational Genomics, Samsung
GEL-positive pancreatitis was seen in 9% (15/165) of HPs, including Medical Center, Republic of Korea
ductal epithelial (5/15, 33%) and acinar (4/15, 27%) neutrophilic infiltra-
tions and neutrophils in duct lumen (8/15, 53%). Abdominal pain was Background & Objectives: Epithelioid hemangioendothelioma(EHE) of
commonly observed in patients with GEL-positive pancreatitis of HPs liver is a rare vascular tumour having variable clinical course, from stable
(11/15, 73%). disease to fatal outcome. Although histologic features are distinctive, EHE
Results: GEL-positive pancreatitis was more commonly observed in HPs with marked cytologic atypia can mimic epithelioid angiosarcoma. EHEs
having symptoms (P=0.038) and showing larger size (P=0.027), infiltra- have been known to have chromosomal translocations involving 1p36.3 and
tive growth pattern (P=0.036), interstitial fibrosis (P=0.007), and lym- 3q25, resulting WWTR1-CAMTA1 fusion gene. Nuclear expression of
phoid cuffs (P=0.001). Periductal lymphoplasmocytic infiltration and fi- CAMTA1 by immunohistochemistry was reported in about 90% of EHEs
brosis (P < 0.001, both), acinar-ductal metaplasias (ADMs; P=0.013), in multi-organ. Our study aims to validate diagnostic utility of CAMTA1
and pancreatic intraepithelial neoplasia/intraductal papillary mucinous expression for EHEs, especially in liver.
neoplasms (PanIN/IPMN; P=0.004) were more commonly seen in HPs Methods: Pathology database of Samsung Medical Center, Seoul, Korea,
with GEL-positive pancreatitis than those without GEL-positive pancre- was queried for all biopsy and resected specimen of hepatic EHEs from
atitis. IBD was present only in one patient without GEL-positive pancre- June 2000 to December 2018. A total of 24 EHE patients were found
atitis in HP. including 9 surgical resections and 20 biopsy specimens (5 of which
Conclusion: In conclusion, GEL can be seen in HPs without clinical underwent both procedures). For control, 13 hepatic angiosarcomas were
evidence of AIP, so this is not specific diagnostic criteria of type 2 AIP. selected. Immunohistochemistry was performed using anti-CAMTA1 an-
tibody (Novus Biologicals, Littleton, CO, USA) in total 37 tumours (24
hepatic EHEs and 13 angiosarcomas).
PS-21-015 Results: 22 of 24 (91.6%) hepatic EHEs showed nuclear staining for
Prognostic impact of the modifications of the 8th versus 7th edition of CAMTA1. One of two CAMTA1-negative cases showed TFE3 positiv-
AJCC staging system, regarding hepatocellular carcinoma ity. The other one case was negative for TFE3. Meanwhile, all 13
C. Satala1, S. Gurzu2, Z. Kovacs3, L. Banias2, I. Jung3 angiosarcoma cases showed negativity for CAMTA1.
1
Clinical County Emergency Hospital, Targu Mures, Romania, Conclusion: CAMTA1 can be helpful in differential diagnosis of hepatic
2
University of Medicine, Pharmacy, Sciences and Technology, Targu vascular tumours, especially in a small biopsy specimen, that have over-
Mures, Romania, 3 University of Medicine, Pharmacy, Sciences and lapping morphology between EHE and angiosarcoma.
Technology, Targu Mures, Romania

Background & Objectives: Representing the 4th cause of cancer-related PS-21-017

death worldwide, hepatocellular carcinoma (HCC) represents a global Evaluation of the American Joint Committe on Cancer (AJCC) 8th
health problem. The aim of our study was to emphasize the prognostic edition staging system for hepatocellular carcinoma in 1,034 patients
impact of differences between the 8th vs. 7th edition of AJCC staging with curative resection
system of HCC. H. Jung1, S. Ha1
1
Methods: All consecutive HCCs diagnosed in the Pathology Department Department of Pathology and Translational Genomics, Samsung
of Clinical County Emergency Hospital of Targu-Mures Romania, during Medical Center, Republic of Korea
 Virchows Arch

Background & Objectives: Recently, 8th edition staging system of the Background & Objectives: ATRX and SSTRs have been defined as
American Joint Committee on Cancer (AJCC) was released with change prognostic and therapeutic markers for PanNETs. We examined these
in T stage. We validated the prognostic value of the new AJCC staging markers in our data set, along with the markers for organ of origin.
system in comparison to the previous 7th edition. Methods: TMAs prepared from thirty consecutive resection specimens
Methods: Total 1,034 patients who had undergone curative resection as the between 2013-2019. SSTR2A, ATRX, Islet 1, CDX2, and TTF1 were
initial treatment for hepatocellular carcinoma at Samsung Medical Center, applied with immunohistochemistry. Membranous and/or cytoplasmic
between 2008 and 2012, were enrolled. Pathology T stage was determined staining for SSTR2A, and nuclear staining for the other markers were
as AJCC 7th and 8th edition, respectively. Recurrence free survival (RFS) noted.
was estimated using the Kaplan-Meier method and compared by log-rank Results: F/M: 19/11. Mean age: 52. Mean survival: 29 mos (6-70). 11
test. The analysis of the time dependent receiver-operating-characteristic were G1, 18 were G2, and 1 was a G3(NEC). ATRX lost in 18, SSTR2
(ROC) curves for censored survival data was used to compare the capability negative in 3, CDX2 positive in 7, Islet-1 negative in 5 cases, and TTF1
of the two models to predict tumour recurrence. negative in all. The mean diameter in ATRX lost ones was 5 cm, and 2 cm
Results: Stage migration was observed in 63 patients (6.3%); from T2 to in ATRX retained cases (p:0.01). 3/7 CDX2 positive cases were R1.
T1a in 45 patients and from T3 to T4 in 20 patients. For solitary tumours ATRX lost in 9/11 with node metastasis, 7/9 with LVI, and 7/10 with
≤2cm(T1a by 8th), those with microvascular invasion had shorter PNI. NEC case lost ATRX, was positive with SSTR2 and Islet1. 2/3
RFS(p=0.016). Tumours involving a major branch of portal vein or he- SSTR2 negative cases had long survivals (59 & 70 mos). Death seen in
patic vein(T4 by 8th and T3b by 7th, n=20) showed shorter RFS than 1/30 with loss of ATRX, positive SSTR2 and negative Islet1, and CDX2.
multifocal tumours at least one of which is >5cm(T3 by 8th and T3a by Conclusion: Even though no significant statistical results were found,
7th, n=40)(p=0.017), supporting the change in 8th edition. loss of ATRX seems to be common in cases with worse pathological
Conclusion: The AJCC 8th edition staging system for HCC showed com- prognostic parameters such as larger tumours, lymph node metastasis,
parable predictive performance to the 7th edition. It is desirable in future lymphovascular and perineural invasion. SSTR2 was positive in almost
revision to consider sub-stratification of solitary tumours ≤2cm(T1a) de- all cases and even the negative ones had long survivals. One should not
pending on the presence of vascular invasion, which is not included in 8th count on Islet1 and CDX2 to prove the pancreatic origin.
edition. Further studies are required to validate these findings.

PS-21-020
PS-21-018 Incidental diffuse hepatic angiosarcoma in a liver explant - a case
Role of liver biopsy in the management of liver diseases following the report of an uncommon presentation of a rare liver neoplasia
end of interferon era: experience of a tertiary referral center N.J. Lamas1, M. Oliveira1, L. Ferreira1, C. Fleming1, R. Amorim2, B.
N. Ehsan1, D. Sweed1, E. Karman2, E.A. Abdelsameea1, A. Mohamed1, Fernandes2, J.R. Brandão2, A. Coelho1, J.R. Vizcaíno1
M. Elsabaawy1 1
Anatomical Pathology Service, Department of Pathology, Hospital and
1
National Liver Institute - Menoufia University, Egypt University Center of Porto, Portugal, 2 Centro Hospitalar do Porto,
Portugal
Background & Objectives: Liver biopsy is the cornerstone for the manage-
ment of patients with liver diseases. During the interferon era for the treatment Background & Objectives: Primary angiosarcoma of the liver, although
of chronic hepatitis C patients, liver biopsy was mandatory for evaluating the rare, is the most common malignant mesenchymal hepatic tumour, with
degree of necroinflammation activity and the stage of fibrosis. The develop- aggressive behaviour and dismal prognosis. It is a high-grade malignant
ment of direct acting antiviral agents for hepatitis C virus made liver biopsy neoplasm of endothelial cells of blood or lymphatic vessels, affecting
less required. The purpose of this study was to explore the role of liver biopsy more men than women, with peak incidence in the 6th-7th decades of life.
related to adult liver disease following the end of the interferon era. Methods: We report the case of a 54-year-old male diagnosed with
Methods: Pathology and medical records of patients who had underwent alcohol-related hepatic cirrhosis. The computed tomography scan showed
needle liver biopsy from January 2015 through December 2018 were a dysmorphic liver with lobulated contours and heterogeneously diffuse
collected. Liver biopsy taken for evaluation of donor liver histology, post density, without focal lesions. After several episodes of clinical deterio-
liver transplant or focal lesion was excluded from the study. ration, the patient underwent liver transplantation.
Results: A total of 275 liver biopsies were collected, 191 males and 84 Results: A liver specimen weighing 1273g and measuring
females with mean age 41.22±13.36. The pathological diagnosis was as 25x13x11,5 cm was received. The external surface was smooth
follows 48 drug induced liver injury, 38 Non-alcoholic fatty liver disease, and lobulated. Upon section, the liver was globally multinodular
34 chronic hepatitis B or hepatitis C with cholestasis, 29 autoimmune with multiple nodules of small size. Throughout the liver paren-
hepatitis, 26 primary sclerosing cholangitis, 8 primary biliary cholangitis, chyma, within the nodular regions, there were some vague greyish
7 autoimmune overlap syndrome, 13 ascending cholangitis, 13 active areas, the largest measuring 4,5x3 cm; and numerous ill-defined
bilharziasis, 10 Wilson’s disease, 11 sarcoidosis, 10 cytomegalovirus/ reddish areas, the largest measuring 4x3 cm. A 0,5 cm lymph node
Epstein-Barr virus infection, 7 Dubin Johnson syndrome, 6 liver abscess, was isolated from the peri-hilar region. The histological analysis
4 resolving acute hepatitis. Solitary cases of latent congenital hepatic revealed a cirrhotic liver with fibrous bridges containing ductular
fibrosis, amyloidosis, hemochromatosis, hepatic amoebiasis, malaria, proliferation and linfomononuclear infiltrate. In the greyish and
polyarteritis nodosa, myeloproliferative disease were noticed. Four cases reddish areas one observed multiple foci of marked proliferation
of non-specific hepatitis were also seen. Initial diagnosis was made by of atypical large sized endothelial cells, with hyperchromatic nuclei
liver biopsy and confirmed by laboratory investigations. and increased pleomorphism. Mitosis were frequent and atypical.
Conclusion: Liver biopsy remains to be an integral component for the Focally, the lesion conditioned atrophy and destruction of the
hepatologist’s diagnostic decision. neighboring hepatic parenchyma. In other areas, there were dilated
sinusoids filled with blood and containing small aggregates of neo-
plastic cells with papillary-like morphology. The lymph node iso-
PS-21-019 lated from the peri-hilar region was unremarkable. The immuno-
Prognostic immunhistochemical parameters of pancreatic neuroen- histochemistry study showed neoplastic cells positive for Factor
docrine neoplasms (PanNETs) VIII, ERG, CD31, p53 (aberrant overexpression) and c-Myc. The
B. Keskin1, E. Bozkurtlar1, P. Bagci1 estimated proliferative index (%Ki-67) was above 50%. A diagno-
1
Marmara University, Turkey sis of hepatic angiosarcoma was made.
Virchows Arch

Conclusion: This case reports an incidental presentation of a rare aggres- of 68 cases of periampullary cancers were assembled. The expression of
sive liver neoplasm. total RON, c-MET and PD-L1 protein has been analysed by immunohis-
tochemistry. The association between a positive expression of RON and
clinicopathologic features was analysed.
PS-21-021 Results: 24 cases showed dominant expression of RON protein in the cancer
Large tumour size, lymphovascular invasion, and synchronous me- relative to adjacent normal epithelium. Another 23 cases showed aberrantly
tastasis are associated with recurrence of solid pseudopapillary decreased expression and the other 20 cases showed unremarkable expression
neoplasm of RON protein between cancer tissue and normal one. An association was
G. Lee1, Y. Sung1,2, J.H. Lee3,2, K. Song3,2, D.W. Hwang3,2, S.S. Lee4,2, identified between the poor prognostic factors and the expression of RON. No
D. Seo4,2, S.K. Lee4,2, S.C. Kim3,2, E. You1, S. Hong1,2 significant association was identified between RON overexpression and c-
1
Department of Pathology, Asan Medical Center, Republic of Korea, MET or PD-L1 overexpression. There was significant association between
2
University of Ulsan College of Medicine, Republic of Korea, the expression of RON and patient survival. (p=0.034)
3
Department of Surgery, Asan Medical Center, Republic of Korea, Conclusion: We suggest that RON plays an important role in aggressive
4
Department of Gastroenterology, Asan Medical Center, Republic of behaviour of periampullary cancers. This finding provides additional un-
Korea derstanding of the biology of the RON in periampullary cancer and has
have implications for therapeutic strategies to target RON activity.
Background & Objectives: Solid pseudopapillary neoplasms (SPNs)
of the pancreas have low malignant potential. However, our under- This work was supported by the National Research Foundation of
standing of malignant SPNs is limited. The purpose of this study Korea(NRF) grant funded by the Korea government (No. NRF-
was to 1) to identify the proportion of malignant SPNs after re- 2017R1C1B5015417).
moving non-relevant malignant factors, and 2) to identify factors
investigate risk factors of recurrence in malignant SPNs.
Methods: To evaluate risk factors affecting malignant potential, 376 sur- PS-21-023
gically resected SPN cases were reviewed and compared with clinico- Sinusoidal platelet obstruction is associated with portal hypertension
pathologic features. in myeloid metaplasia of the liver
Results: Mean patient age was 35.1±13.5 years-old with a male to female A. Normand1, Y. Le Bris2, E. Frampas3, J. Gournay4, J. Mosnier1
1
ratio of 0.25. SPNs were predominantly located in body and tail (261 cases, Hotel Dieu de Nantes, Department of Pathology, France, 2 Hotel Dieu de
69.6%) with mean size of 4.6±2.8 cm. Forty-eight cases (12.8%) were Nantes, Haematology Laboratory, France, 3 Hotel Dieu de Nantes,
malignant SPNs, and 26 of which (54.2%) had perineural invasion and Department of Radiology, France, 4 Hotel Dieu de Nantes, Department
19 (40.0%) had lymphovascular invasion, respectively. Invasion to adjacent of Gastroenterology, France
organs was noted in 11 cases (22.9%). Three (6.3%) had synchronous liver
metastasis, one (2.1%) had lymph node metastasis, and one (2.1%) had Background & Objectives: To study liver histological lesions associated
omentum metastasis. Recurrence was observed in 9 cases (18.8%), and with portal hypertension (PH) in myeloid metaplasia (MM).
was associated with higher pT category (p=0.02), lymphovascular invasion Methods: Between 2012 to 2018 liver biopsies with MM were retrieved
(p<0.01), and synchronous metastasis (p<0.001). Patients with malignant from Pathology Department. Clinical, hematological and imaging data
SPNs had significantly worse recurrence-free survival (10 year survival were collected. All biopsies were reviewed and lesions described in portal
rate, 73.2%) than those with benign SPNs (96.3%, p=0.01). Other factors, hypertension without cirrhosis were studied: peri-sinusoidal fibrosis (PF),
including higher pT category (p=0.02), synchronous metastasis (p<0.01), sinusoidal dilatation (SD), obliterative portal venopathy (OPV), nodular
and lymphovascular invasion (p<0.01) also showed worse recurrence-free regenerative hyperplasia (NRH). Immunostaining for CD31 expression
survival by univariate analysis. Worse prognostic factor for recurrence was and JAK2/CALR/MPL mutations detection was performed.
lymphovascular invasion (p=0.02). Results: We have included 17 patients with MM among them 10 patients
Conclusion: Malignant SPNs were observed in 13% of SPNs. Even (59 %) with PH (oesophageal varices, ascites or raised portal gradient). In
SPNs were malignant, they had far better 10 year recurrence-free survival this sub-group we observed SD (n=10), PF (n=9), NRH (n=5), OPV
than other malignant pancreatic tumours. Recurrence of SPNs was asso- (n=3) and CD31+ sinusoïdal platelet obstruction in 3 patients.
ciated with increased tumour size, lymphovascular invasion, and syn- Myeloproliferative neoplasm (MPN) was diagnosed in 6 patients with
chronous metastasis. Lymphovascular invasion was a worse prognostic PH and all of them showed PF, 3 cases showed extrahepatic portal vein
factor in malignant SPN patients. thrombosis, 3 NRH, 1 OPV and 2 sinusoidal platelet obstruction.
JAK2V617F mutation was detected in 83% of MPN patients. All mutated
patients have portal vein thrombosis or NRH. Chronic myelomonocytic
PS-21-022 leukemia-2 was diagnosed in one case with PH. Sinusoidal platelet ob-
The prognostic value of the RON expression in the periampullary struction was detected in this patient and in another. The latter had PH but
cancers neither portal vein thrombosis (PVT) nor proven MPN. No CALR or MPL
S. Lee1, Y. Kim1, C. Cho1, H. Oh1, W. Sung1 mutations were found in this series.
1
Department of Pathology, Catholic University of Daegu School of Conclusion: MM is not constantly associated with PH which is explained
Medicine, Republic of Korea by other causes: in these patients, PH is frequently associated with extra-
hepatic PVT or NRH. In lacking of these anomalies, intra-hepatic sinu-
Background & Objectives: With an increase in the knowledge of soidal platelet obstruction might explain PH.
recepteur d’origine nantais (RON) receptor tyrosine kinase function in
different types of human cancers, it is becoming clear that RON has
prominent roles in both cancer cells and associated microenvironment. PS-21-024
These understandings of this oncogene make it an exciting therapeutic Non-alcoholic fatty liver disease (NAFDL) - a retrospective study in
target. In this study, we investigate the expression pattern of RON in paediatric liver biopsies
human periampullary cancer and correlate the findings with the clinico- T. Oğuzsoy1, H. Sahin Ozkan2, C. Celikel3
1
pathologic parameters. Marmara University Training and Researching Hospital, Turkey,
2
Methods: 72 cases of totally resected specimen for periampullary cancer Marmara University Faculty of Medicine, Department of Pathology,
from January 2003 to December 2014 were reviewed. Tissue microarrays Turkey, 3 Marmara University Faculty of Medicine, Turkey
 Virchows Arch

Background & Objectives: Non-alcoholic steatohepatitis(NASH) is a Conclusion: The introduction of the techniques of Aniline Blue and
morphological pattern of liver injury that is characterised by hepatocellu- Sudan III-IV in the intraoperative study in liver transplant allows a more
lar steatosis, ballooning and lobular inflammation. Our aims were to objective and sensitive study to detect possible alterations that show the
evaluate the distribution of morphological features, to determine organs, being specific techniques enhance the fibrous lesions and steatotic
NAFLD activity score (NAS) and SAF score, and to observe the effect lesions that we must study and its application does not significantly in-
of morphological changes on fibrosis, in paediatric age group. crease the time of histological study and in case of diagnostic doubt are
Method : The biopsies of patients diagnosed as NAFLD under 18 years of techniques that can offer a more reliable diagnosis.
age, between 2014 and 2016, were retriewed from the archives of the
Marmara University School of Medicine. Supported by Servicio Murciano de Salud (SMS).
Methods: The biopsies of patients diagnosed as NAFLD under 18 years
of age, between 2014 and 2016, were retriewed from the archives of the
Marmara University School of Medicine. PS-21-026
Results: We analysed 45 liver biopsies. Due to insufficient biopsy, 3 Diagnostic accuracy of an immunohistochemical panel to distinguish
cases were excluded from the study. Among 42 patients, the mean age intrahepatic cholangiocarcinoma from bile duct adenoma
was 11.9 and 28(%66.6) were male. The degree of steatosis was scored as L. Nicolè1, S. Sarcognato1, R. Cappellesso1, T. Sanavia2, C. Luchini3, C.
1 for 10, 2 for 8, and 3 for 24 cases. The distribution of steatosis were Mescoli1, P. Capelli3, A. Fassina1, M. Guido1
1
panacinar in 14(%33.3), azonal in 11(%26.1), peri-portal in 8(%19), peri- University of Padua, Italy, 2 Harvard Medical School, USA,
3
central in 8(%19) and limited to zone 2 in 1 case. The lobular inflamma- University of Verona, Italy
tion score was 0 in 4 cases, 1 in 17 cases, 2 in 12 cases and 3 in 9 cases.
Ballooning degeneretion were evident in 21 patient, being mild or prom- Background & Objectives: Differential diagnosis between intrahepatic
inent in 18 and 3 of biopsies, respectively. No fibrosis was observed in 16 cholangiocarcinoma (ICC), an aggressive liver tumour, and bile duct
cases, whereas 15 were stage 1c, 7 were stage 2 and 4 were stage 3. In adenoma (BDA), an indolent lesion, is fundamental but sometimes chal-
statistical analysis fibrosis was statistically related to the distribution of lenging, particularly for well-differentiated ICC. Morphological analysis
steatosis (p< 0.01), NASH score (p<0.001) and lobular inflammation alone is often not sufficient to achieve a correct diagnosis. Several immu-
(p<0.01), but not with the degree of steatosis and/or ballooning. nohistochemical markers have been proposed to improve the diagnostic
Conclusion: Although ballooning degeneration is accepted as the performance, but all of them, taken singularly, showed a low sensitivity
hallmark feature of NASH, in our study it was not related to the and are not used in clinical practice. Moreover, only a few studies focused
degree of fibrosis. In contrast, the distribution but not the degree on the differential diagnosis between ICC and BDA, so far.
of steatosis and lobular inflammation w ere both correlated with The aim of this study was to investigate the diagnostic performance of a
the degree of fibrosis. 3-marker panel, including p53, p16INK4a, and S100P, to evaluate whether
their combination might help to distinguish ICC from BDA.
Methods: Fifty-two surgically resected liver nodules (30 ICCs and 22
PS-21-025 BDAs) were retrospectively selected and stained with p53, p16INK4a, and
Histochemical techniques applied in freezing cuts during intraoper- S100P. p53 was considered positive when a strong nuclear immunoreaction
ative biopsies in liver transplantation was observed, while p16INK4a and S100P positivity was both nuclear and
A. Salazar Nicolas1, M.I. Ortuño Moreno1, L. Barona Garcia1, A. cytoplasmic. An algorithm was built and its diagnostic performance analysed.
Caballero Illanes1, N. Villa Lorente2, M.A. Menárguez Arnaldos3, M.D. Results: As expected, despite their perfect specificity (100%), all the
Perez Caparros4, G. Ruiz Garcia1, M.I. Oviedo Ramirez5, E. Martinez evaluated markers showed a low sensitivity when considered singularly
Barba1 (56.7%, 26.6%, 23.4%, for p53, p16INK4a, S100P, respectively). On the
1
Servicio de Anatomía Patológica. Hospital Clínico Universitario Virgen contrary, the algorithm based on the sequential use of p53, p16INK4a, and
de la Arrixaca., Spain, 2 Servicio de Anestesia y Reanimación. Hospital S100P, showed a sensitivity of 73.4%, a specificity of 100% and an
Clínico Universitario Virgen de la Arrixaca., Spain, 3 Servicio de overall accuracy of 84.6%.
Urgencias. Hospital Clínico Universitario Virgen de la Arrixaca., Spain, Conclusion: The adopted 3-marker algorithm is helpful in differentiating
4
Servicio de Ginecología y Obstetricia. Hospital de Mèrida., Spain, ICC from BDA. Further larger studies are needed to validate the proposed
5
Servicio de Anatomía Patológica. Hospital Clínico Universitario algorithm.
Virgen de la Arrixaca., Spain

Background & Objectives: The introduction of more extended clinical PS-21-027

criteria when considering the suitability of a donor has led to an increase Pancreatic neuroendocrine microadenomatosis: clinicopathologic
in the number of transplants, especially kidney transplants, and this im- features of 5 cases
plies a rise in intraoperative biopsies performed in the pathology depart- D. Unal Kocabey1, E. Cakir1, F.H. Dilek1, I. Aydin1
ment. Given this growth in transplants from “not ideal donors“ makes the 1
Izmir Katip Celebi University Ataturk Training and Research Hospital
histological study should be more precise, optimal and objective. Department of Pathology, Turkey
Methods: 18 cases of intraoperative biopsy of liver transplantation be-
tween the months of December and January of 2018-2019 were studied. Background & Objectives: The presence of multiple small neuro-
The samples were stained with Hematoxylin-Eosin and 2 histochemical endocrine tumours (NET) in pancreas measuring less than 0.5 cm
techniques were applied: Chromotrope Aniline Blue to enhance fibrosis in greatest dimension has been referred to as pancreatic
and Sudan III- IV for the study of hepatic steatosis, comparing the results microadenomatosis (PMA). PMA has been considered the precur-
obtained in each of boths techniques. sor of NET. PMA can occur sporadically or be associated with
Results: In the study of fibrosis comparing HE and Aniline Blue, 4 cases syndromes such as multiple endocrine neoplasia type 1 syndrome
showed a greater lesion in their study with Aniline (22.2%), 6 cases with a (MEN1) and von Hippel-Lindau (VHL) disease. We report the
diagnosis of lesion of lesser degree (33.3%) and 8 presented similar le- clinical and histopathological features of 5 cases diagnosed as
sions between HE and Anilina (44.4%). Regarding the study of PMA.
macrovesicular steatosis with HE and Sudan III-IV, 5 cases showed a Methods: Five cases diagnosed as PMA at our Institution over a 2-year
greater injury with the Sudan technique (27.78%), 4 cases with lesion period were analysed retrospectively. Clinical and demographic data were
of lesser degree (22.2%) and 9 showed a similar injury (50%). retrieved from the hospital records.
Virchows Arch

Results: The patients included two male and three female. Patient Background & Objectives: Angiomyolipomas were reported in many
age ranged from 52 to 74 years. All patients underwent different locations. In the gallbladder, only one case of “edematous
pancreaticoduodenectomy. One of 5 patients exhibited MEN1 and angiomyolipoma-like polyp”, 3 primary malignant PEComas and 1 me-
had well-differentiated NET in duodenum and parathyroid adeno- tastasis from malignant PEComa have been described in literature. We
ma. Two patients presented with accompanying well-differentiated report a case of gallbladder angiomyolipoma, with long follow-up.
NET in pancreas. One patient exhibited accompanying well- Methods: A 58-year-old woman was admitted with abdominal pain, nausea
differentiated adenocarcinoma in ampullary region. The remaining and vomiting. Ultrasound scan showed a distended gallbladder with a suspect
patient had no concomitant tumour and suffered from an stone embedded in the neck region. A laparoscopic cholecystectomy was
insulinoma syndrome. Histopathologically, all PMA displayed a performed. The gallbladder measured 6.5 cm in length and presented a
trabecular or mixed solid-trabecular growth pattern. Two of accom- 2.0x1.5x1.2 cm white-grayish nodule in the neck region wall. No stones were
panying well-differentiated NET were G1 with the size of 1.3 cm found.
and 0.4 cm and one was G2 with the size of 2.5 cm. Results: A well-circumscribed, unencapsulated tumour, was composed
Conclusion: PMA is a rare entity and may be detected as an incidental by sheets of spindle and plump epithelioid cells with abundant pale eo-
finding in patients with pancreatic tumour. It is not restricted to genetic sinophilic cytoplasm, and a rich vascular network. Tumour cells were
syndromes such as MEN1; it may also occur independently from this positive for HMB-45, actin and desmin; negative for CD117 and CD34.
inherited condition. Further studies with larger case series are needed to S100 was positive in rare mature fat cells within the neoplasm. Ki67
elucidate the etiopathogenesis of these lesions. proliferation index was 1%. A diagnosis of extrarenal angiomyolipoma
was made. Chronic cholecystitis and pseudopyloric metaplasia were also
present. No additional lesion was identified after a subsequent CT scan,
PS-21-028 and the patient remains free of disease ten years after the diagnosis.
Hepatocellular carcinoma in non-cirrhotic liver: a retrospective clin- Conclusion: Mesenchymal tumours of the extrahepatic bile ducts may
icopathological study of 55 cases show PEC (perivascular epithelioid cell) differentiation. The identifica-
M. Varela dos Santos1, A. Figueiredo2, A.M. Carvalho2, S. Silva3 tion of an angiomyolipoma in the gallbladder is not surprising because
1
Serviço de Anatomia Patológica - Centro Hospitalar e Universitário de similar lesions are described in liver, pancreas and, occasionally, in the
Lisboa Central, E.P.E., Portugal, 2 Serviço de Anatomia Patológica - common bile duct. The presence of a stenosing tumour in the neck region
Hospital Curry Cabral, Centro Hospitalar e Universitário de Lisboa may have induced the symptoms in absence of obstructing stones.
Central, E.P.E., Portugal, 3 Serviço de Cirurgia Geral - Hospital Curry
Cabral, Centro Hospitalar e Universitário de Lisboa Central, E.P.E,
Wednesday, 11 September 2019, 09:30 - 10:30, Agora 3
Portugal
PS-22 | Endocrine Pathology
Background & Objectives: Liver cirrhosis is the main risk factor for
Hepatocellular Carcinoma (HCC), but a smaller number of HCCs arise in
non-cirrhotic livers (NCL): albeit some etiological factors have been de- PS-22-001
scribed, the development of HCC without cirrhosis has been a subject of Adrenal myelolipomas: case series
debate, and its pathophysiology is still largely unknown. E. Gun1, A. Avci1, S.D. Altindag1, D. Etit1
1
The main goal of this study was to investigate the clinical and pathologic Izmir Katip Celebi University Ataturk Training and Research Hospital,
features of HCC in NCL. Department of Pathology, Turkey, and Research Hospital, Department of
Methods: A retrospective medical record and pathological review was Pathology, Turkey
conducted for all cases of HCC in NCL that were subjected to liver
surgery in our Medical Centre between January 2013 and December Background & Objectives: Adrenal myelolipomas are rare, benign neo-
2017. Demographic data, clinical course pre and post treatment, labora- plasms consisting of mature fat tissue and hematopoietic elements resem-
tory results and pathologic findings of all cases were analysed. We used bling bone marrow. They constitute approximately 2,5% of all primary
nonparametric tests for statistical analysis, and a p value ≤0.05 was con- adrenal gland tumours. They are usually unilateral with regular borders
sidered statistically significant for all tests. and variable in size. We aimed to review these cases we encounter in our
Results: Age ranged from 19 to 96 years (median 74) and 76,36% were daily practice.
male. Alcoholism (27%), diabetes (25%) and HCV-infection (16%) were Methods: All the patients with adrenal myelolipomas who were operated
the most common clinical factors. Steatosis (27,3%), chronic viral hepa- in our hospital between January 2008 and July 2018 were evaluated
titis (21,8%) and steatohepatitis (5,45%) were the most frequent patho- retrospectively. Demographic characteristics, size, laterality and other as-
logical findings in non-tumoural liver. The neoplasms had the usual his- sociated lesions were recorded.
tology. 7,27% of all HCCs were fibrolamellar carcinomas. Recurrence Results: A total of 21 adrenal myelolipoma cases were detected, account-
occurred in 27 patients (49%), but showed no significant association to ing for 4,9% of all adrenal lesions. Sixteen (76,2%) of the cases were
vascular invasion, histological grade or TNM staging. female and 5 (23,8%) were male. The mean age was 50,4 (23-70). While
Conclusion: HCC in NCL is still a poorly understood and heterogeneous 15 (71,4%) of the cases were localized in the right adrenal gland, 6
neoplasm: in our series, these tumours were mostly found in elderly male (28,6%) were localized on the left side. The mean diameter of the lesions
individuals, and had the usual morphological features of HCC. Most was 6 (1-17) cm. The most common accompanying lesion was adrenal
patients had normal non-tumoural parenchyma. HCV-hepatitis and alco- cortical adenoma with 3 cases, followed by adrenal hyperplasia, adrenal
hol consumption may be risk factors for this neoplasm. Recurrence was endothelial cyst and pheochromocytoma with 1 case. Macroscopically,
common but nondependent of any of documented variables. the lesions consisted of whitish, fibrotic areas within mature adipose
tissue-like areas. Histopathologically, the dominant component was lipo-
ma in the majority of cases.
PS-21-029 Conclusion: Adrenal myelolipomas are very rare lesions, often seen as
Angiomyolipoma of the gallbladder. A case report with 10-year fol- small tumoural foci accompanying other tumours or as space-occupying
low-up masses alone. Although these tumours do not need to be removed in the
F. Liberati1, L. Ventura2 treatment because there is no mass effect, we have reviewed all of the
1
Division of Pathology, San Camillo De Lellis Hospital, Rieti, Italy, cases we have encountered since they are observed more frequently than
2
Division of Pathology, San Salvatore Hospital, L'Aquila, Italy expected.
 Virchows Arch

PS-22-002 EWSR1 rearrangement when 5% or more of the nuclei with the break-
The evolving understanding of noninvasive follicular thyroid neo- apart signal were detected. Analysis of the presence of TERTp mutations
plasm with papillary-like nuclear features (NIFTP) - lessons from (-124C>T and -146C>T) was performed by Sanger sequencing in a
surgical pathology and cytopathology series from Asia CEQ8000 Beckman Coulter Sequencer.
A. Bychkov1, C.K. Jung2,3, H. Vuong4, Z. Liu5, K. Kakudo6 Results: No recurrence, metastases or death occurred in any of the pa-
1
Department of Pathology, Kameda Medical Center, Kamogawa City, tients followed during an average of 33.4 months (range 12-72). EWRS1
Chiba, Japan, 2 Department of Hospital Pathology, College of Medicine, rearrangements were detected in the four cases tested (one case not tested
The Catholic University of Korea, Seoul, Republic of Korea, 3 Cancer for EWSR1). In only one of the five patients (a 66 year-old female) was a
Research Institute, College of Medicine, The Catholic University of TERTp mutation (-124C>T) detected.
Korea, Seoul, Republic of Korea, 4 Department of Pathology, Conclusion: Our results suggest the participation of EWSR1 rearrange-
University of Yamanashi, Chuo, Yamanashi, Japan, 5 Department of ments in the tumourigenesis of HTT. TERTp mutations are not always
Pathology, School of Basic Medical Sciences, Cheeloo College of associated with malignant tumours.
Medicine, Shandong University, Shandong, China, 6 Department of
Pathology, Kindai University Nara Hospital, Japan This work was supported by Grant PI15/01501-FEDER from Instituto de
Salud Carlos III, Ministry of Science, Innovation and Universities, Spain.
Background & Objectives: The introduction of noninvasive follicular
thyroid neoplasm with papillary-like nuclear features (NIFTP) was initi-
ated by pathologists. The Asian Working Group (WG) in Thyroid PS-22-004
Pathology performed several NIFTP projects based on data collected Eighteen-year history of medullary thyroid carcinoma at Centro
from Japan, Korea, China, India, and several ASEAN countries. The Hospitalar Universitário de São João, Porto, Portugal (2000-2018)
original surgical pathology (26,604 thyroid cancers) and cytopathology T. Cardoso Lima da Costa Pereira1, D. Pereira de Melo1, J. Magalhães1
1
(11,372 thyroid nodules) series from the Asian WG and meta-analysis of Centro Hospitalar Universitário de São João, Portugal
existing literature are the core datasets of this study.
Methods: Our original data and the results of a meta-analysis suggest that Background & Objectives: Medullary thyroid cancer (MTC) is a neu-
the initial rate of NIFTP was overestimated, averaging 8.5% (95% CI roendocrine tumour of the parafollicular or C cells of the thyroid gland.
5.8–11.6%) of all thyroid cancers worldwide. We found that the incidence Most MTCs are sporadic, however, approximately 25 percent are famil-
of NIFTP in the Asian cohorts (2.6%, 11 studies) is significantly lower ial, mostly as part of the multiple endocrine neoplasia type 2 (MEN2)
than that reported in American (12.2%, 26 studies), European (11.5%, 9 syndrome. Also, in most patients, the disease was already metastasized at
studies) or combined non-Asian series (11.9%, 35 studies). We identified the time of diagnosis. We wanted to compare the experience in our
several contributing factors to such discrepancy. Instituteion with the literature and determine how many cases were spo-
Results: Difference in the prevalence is due to various histological radic, which were associated with MEN2 syndrome and how many had
diagnostic thresholds, different biology of tumours, and distinct metastases at the time of diagnosis.
management strategies (e.g., active surveillance for indeterminate Methods: All cases with diagnosis of MTC registered in our center, from
nodules and NIFTP). The lower prevalence of NIFTP in Asia indi- 2000 until 2018, were collected for review and the following variables
cates a low impact on malignancy risk in cytopathology. Our orig- were analysed: gender, age at diagnosis, size of primary tumour, presence
inal series and further meta-analysis (14 studies, 14,153 resected of RET germline mutation and presence of lymph node metastasis.
nodules) found decrease in risk of malignancy after NIFTP reclas- Results: A total of thirty-nine cases were reviewed (n=39), twenty-two
sification for most of the Bethesda diagnostic categories, which was were female, the mean age was 57,22 years. Average tumour size was
more significant in Western than in Asian practice. 21,26 mm. Six cases had RET mutation (n=6) and ten had lymph node
Conclusion: The incidence of NIFTP was higher in Institutions where metastasis (n=10).
surgical resection rates for cytologically indeterminate nodules were high Conclusion: An eighteen-year review at our center demonstrated that
(r = 0.83; p = 0.02). Recent Asian studies added new knowledge to aid a most MTC occurred in female patients and were neither associated with
better understanding of NIFTP. MEN2 syndrome or with lymph node metastasis.

PS-22-003 PS-22-005
Hyalinising trabecular tumour of the thyroid. A molecular study Surgical treatment of adrenal gland metastasis: a single centre
J.M. Cameselle-Teijeiro1, M. Sanchez-Ares1, J. Caneiro-Gómez1, T.Y. experience
Rico-Rodríguez 1 , R. Pèrez-Becerra 1 , A. Vázquez-Boquete 1 , I. S. Cerovic1, B. Kovacevic1, V. Skuletic1, J. Dzambas1, D. Mikic1
Abdulkader-Nallib1 1
Military Medical Academy, Serbia
1
Clinical University Hospital of Santiago de Compostela, Spain
Background & Objectives: Adrenal glands (AG) are often the site
Background & Objectives: Hyalinizing trabecular tumour (HTT) is a rare of various malignant metastases, especially lung, breast, melanoma,
follicular derived neoplasm. The prognosis is extremely good with only gastrointestinal and kidney cancer. In 30%-70% of patients, chang-
very rare documented cases of distant metastasis. There is controversy es in AG represent incidental findings – incidentalomas, as there is
surrounding its relationship with papillary thyroid carcinoma (PTC), and usually unknown primary malignancy. The average period between
malignant potential. Since EWRS1 rearrangements have recently reported diagnosis of malignancy and the metastases occurring in AG is
in PTC, and TERT promoter (TERTp) mutations are a major indicator of about 2.5 years
poor outcome in differentiated thyroid carcinomas, we investigate these Methods: In 205 patients treated in Military Medical Academy in 2004-
alterations in a series of HTT. 2018, adrenalectomy and/ or adrenalectomy with nephrectomy (due to
Methods: Five cases of HTT were studied from 5 patients, 4 female and 1 renal cell cancer- RCC) were performed. The basic macroscopic and
male, with a mean age of 56 years (range 25-66). All the studies were microscopic parameters were analysed. From the clinical and
performed on 4-ηm paraffin embedded tissue sections of HTT without pathohistological protocols, the time from the beginning of the primary
histological or clinical data of malignancy. Fluorescence in situ hybridi- malignancy treatment to the adrenalectomy has been established.
zation (FISH) was carried out using Vysis EWSR1 Break Apart FISH Statistical analysis was done in the IBM SPSS 24.0 software program,
Probe Kit (Abbott Molecular). Cases were considered positive for with statistical significance for values p<0.05.
Virchows Arch

Results: AG metastases were diagnosed in 37 (17.96%) patients, and GAPP (Grading System of Adrenal Phaeochromocytoma and
and 54.05% were incidental. Statistically significant difference in Paraganglioma) evaluated in parallel in a subgroup of patients of a large
AG mass was in patients with RCC compared to other malignan- ongoing study.
cies (p<0.002). RCC metastases were the most common, 43.24%, Methods: Phaeochromocytomas from 60 patients operated in 2014-19
and 35.13% patients were with lung cancer (LC) metastases. and examined in parallel by both evaluation systems.
Among 17 (47.95%) patients with treated malignancies, adrenalec- The group of patients monitored over the five-year period was gender-
tomy was done averagely after 14.71 months. The shortest time for balanced (M28 / F32).
the occurrence of AG metastases was related to LC statistically The mean age at diagnosis was 52 years with a wide range (22-79); the
significant (p=0.00131). average tumour size (by largest dimension) was 59 mm. These character-
Conclusion: The results of our analysis show that over 50% of patients istics did not differ significantly by gender. Side representation was with-
with unknown primary malignancies have diagnosed metastases in AG. out obvious predilection.
The high prevalence of metastases in AG in patients with known We used image analysis to accurately assess tumour proliferation activity
extrarenal malignancies of 47.95% indicates the need for intensive clin- and tumour cellularity.
ical monitoring. Results: In the PASS score, only a small proportion of tumours were
below the arbitrary threshold of minimal risk of malignancy, these tu-
mours were slightly more frequent in men (PASS <4 [%]: ALL 11.6; M
PS-22-006 17.8; F 6,25).
Genomic landscape of pulmonary carcinoids with high grade The mean GAPP score was 3.15 (0-9) with no significant gender differ-
progression ence (M 3,39 (0-9); F 2,94 (1-8)). The vast majority of tumours in this
J. Cros1, N. Thèou-Anton2, V. Gounant2, R. Nicolle3, C. de Reyes4, A. scoring system were well and moderately differentiated.
Guyard2, L. de Mestier5, S. Brosseau2, Y. Castier2, D. Gentien4, P. There were no major categorization differences between the two systems.
Ruszniewski5, G. Zalcman2, A. Couvelard2, A. Cazes2 Conclusion: In a time-defined probe of 60 patients, we did not find signif-
1
Beaujon University Hospital / Pathology Dpt, France, 2 APHP- Bichat icant differences in the use of PASS and GAPP score in stratification of
University Hospital, France, 3 CIT - Ligue Contre le Cancer, France, morphological risk. We prefer GAPP score for a broader definition
4
Institute Curie, France, 5 APHP- Beaujon University Hospital, France including extraadrenal paragangliomas. The advantage is lower
number of evaluated parameters. The inclusion of functional as-
Background & Objectives: High grade lung carcinoids have been recent- sessment in the GAPP score links the clinical-morphological eval-
ly reported. While they appear to be the thoracic counterparts of grade 3 uation of patients.
neuroendocrine tumours of the digestive tract, there is no molecular data on
such lesions. We aimed to study their genetic landscape including analysis Supported by Ministry of Health of the Czech Republic, grant NV 19-01-
of tumoural heterogeneity. 00083.
Methods: Six patients with a high grade (>20% Ki-67 and/or >10 mito-
ses) thoracic carcinoid were included. We analysed copy number varia-
tions, somatic mutations and protein expression in 9 tumour samples (2 PS-22-010
samples in 3 patients allowed to study spatial/temporal heterogeneity). Clinicopathological features of Warthin-like papillary thyroid carci-
Results: We identified most frequent loss of chromosome 13 (5/6 tu- noma: a case series from a tertiary center
mours), 11 (4/6 tumours) and 3 (4/6 tumours). LOH of tumour suppressor B. Güçlüer1, T. Soylemez1, G. Kir1, A.I. Ozemir2, I. Akalın3
1
genes involved different pathways including chromatin remodelling Istanbul Medeniyet University, Department of Pathology, Turkey,
2
(POLQ, ATR, ARID1A, SETD2, SMARCA2, BAP1, PBRM1, KAT6A), Istanbul Medeniyet University, Department of General Surgery.,
DNA repair (MLH1, ATM), cell cycle (RB1, TP53, LATS2, CDKN2A, Turkey, 3 Istanbul Medeniyet University, Head, Department of Medical
CTNNB1, GSK3B), metabolism (MEN1, VHL). We found somatic muta- Genetics, Turkey
tions of ARID1A in one tumour and of ATM in another tumour.
Comparison of low/high grade areas and of initial/recurrent tumours iden- Background & Objectives: The Warthin-like variant of papillary thyroid
tified an additional mutation of RB1 in high grade area in a patient; an carcinoma (WLPTC) is a rare variant of papillary thyroid carcinoma. The
additional heterogeneous deletion of chromosome 17 with loss of TP53 aim of the study was to analyse the clinicopathological characteristics of
and a new fusion transcript (EIF3E-RSPO2) in recurrent tumour in an- Warthin-like papillary carcinoma of the thyroid gland.
other patient; a TP53 mutation with an additional homozygous deletion of Methods: A total of 176 patients underwent surgical treatment and were
RB1 and loss of Rb protein expression in the high grade area of a third histologically confirmed to have papillary thyroid carcinoma (PTC) at
patient. Goztepe Training and Research Hospital between 2017 and 2019. Of
Conclusion: These data confirm the importance of chromatin remodel- these, 5 (3%) were diagnosed as WLPTC and 4 patients (2%) had varying
ling genes in pulmonary carcinoids and highlight the potential role of proportions of Warthin-like features. Demographic features, gross and
TP53 and RB1 to drive the transformation in more aggressive high grade microscopic findings were recorded. Mutation analysis of KRAS,
tumours. NRAS and BRAF genes was studied in seven cases.
Results: Median patient age was 47years (range: 25–74 years). All cases
were female (100%). Mean tumour size was 14.4 mm (range: 8–21 mm).
PS-22-007 Lymphovascular and perineural invasion was noted in one case and only
Histopathological features in risk stratification of phaeochromocytoma lymphovascular invasion was detected in another case. Ipsilateral central
and paraganglioma patients - comparison of the PASS and GAPP neck lymph node dissection was performed in two cases and lymph node
score metastasis was detected in one case. Extrathyroidal extension was not
J. Dušková1, Z. Musil2, K. Novák3, D. Michalský3, T. Zelinka3 observed. All of them associated with lymphocytic thyroiditis (100%).
1
1st Faculty of Medicine, Charles University, Prague, Czech Republic, Multifocal tumours were found in seven cases. The BRAF mutation de-
2
1st Fac.of Medicine, Czech Republic, 3 1st Fac. of Medicine, tected in four patients, KRAS mutation was present in two patients and
Czech Republic one patient has both BRAF and NRAS mutation.
Conclusion: The WLPTC is an uncommon subtype of papillary thyroid
Background & Objectives: To compare the two risk stratification sys- carcinoma. In the current small series WLPTC has similar histopathologic
tems: PASS (Phaeochromocytoma of the Adrenal Gland Scaled Score) features to classic papillary carcinoma.
 Virchows Arch

PS-22-011 patients with primary hyperparathyroidism (PHPT). This series aimed to

Comprehensive DNA methylation profiling identifies novel diagnos- identify the biochemical and histopathological correlates of Tc-Scan find-
tic biomarkers for thyroid cancer ings in patients with parathyroid adenomas.
C.K. Jung1,2, J. Park3,4,5, S. Jeon6, E. Seo3,4, D.H. Bae3,4, Y.M. Jeong7, Y. Methods: A total of 378 patients with parathyroid adenoma were includ-
Kim1, J.S. Bae8, S. Kim5 and Y.S. Kim3,4 ed. The results of Tc-Scan, histopathological (gland volume, weight,
1
Department of Hospital Pathology, College of Medicine, The Catholic oxyphil cell ratio) and biochemical (blood and 24 hr urine calcium, cre-
University of Korea, Seoul, Republic of Korea, 2 Cancer Research atinine and GFR, PTH, ALP, vitamin D3) variables were recorded.
Institute, College of Medicine, The Catholic University of Korea, Positive Tc-Scan status was referred to adenomas that were localized. A
Seoul, Republic of Korea, 3 Genome Editing Research Center, Korea cut-off of 30% is applied to define adenomas with low (<30%) and high
Research Institute of Bioscience and Biotechnology, Daejeon, Republic (≥%30) oxyphilic cell content. Statistical analyses were performed to
of Korea, 4 Department of Functional Genomics, University of Science assess the relationship among variables.
and Technology, Daejeon, Republic of Korea, 5 Personalised Genomic Results: Tc-Scan localized the abnormal gland in 306 patients.
Medicine Research Center, Korea Research Institute of Bioscience and Parathyroid gland volume and weight, and oxyphil ratio were sig-
Biotechnology, Daejeon, Republic of Korea, 6 Department of nificantly higher in Tc-Scan positive group. Among the biochemi-
Biomedicine & Health Sciences, College of Medicine, The Catholic cal variables, only PTH was found to be significantly increased in
University of Republic of Korea, 7 Department of Biomedicine & Tc-Scan positive group. Binary logistic regression models identi-
Health Sciences, College of Medicine, The Catholic University of fied statistically significant cut-offs for the gland volume (1700
Korea, Seoul, Republic of Korea, 8 Department of Surgery, College of mm3), gland weight (1.3 gr) and PTH levels (170 pg/ml) that can
Medicine, The Catholic University of Korea, Seoul, Republic of Korea be used to predict Tc-Scan positivity.
Conclusion: In addition to PTH levels, this series underscored the impact
Background & Objectives: There are no reliable biomarkers to accurately of cellular composition along with gland volume and weight in the pre-
differentiate indolent thyroid tumours from more aggressive thyroid cancers. diction of Tc-Scan positivity in patients with uniglandular benign para-
This study aimed to develop new DNA methylation markers for diagnosis thyroid disease.
and recurrence risk stratification of papillary thyroid carcinoma (PTC).
Methods: Thyroid tumour-specific DNA methylation profiling was in-
vestigated in 34 fresh frozen tumour tissues which included non-invasive PS-22-014
follicular thyroid neoplasms with papillary-like nuclear features (NIFTP, Prevalence of papillary thyroid carcinoma is significantly higher in
n = 11) and PTC (n = 23), using the Illumina Human EPIC array. We Graves' disease with synchronous nodular thyroid tissue
performed a genome-wide assessment of thyroid tumour-specific differ- M. Kefeli1, H. Gücer2, E.T. Durmuş3, A. Atmaca3, R. Çolak3, O.
entially methylated CpG sites, then validated the top candidate markers in Mete4,5,6
1
206 paraffin tissue samples comprised of follicular adenomas (n = 46), Ondokuz Mayıs University, Department of Pathology, Turkey,
2
NIFTPs (n = 57), and PTCs (n = 103), by pyrosequencing. Department of Pathology, Recep Tayyip Erdogan University, Rize,
Results: Three selected markers differentiated non-malignant (NIFTP and Turkey, 3 Department of Endocrinology and Metabolism, Ondokuz
follicular adenoma) tumours from PTCs with area under the Receiver Mayis University, Samsun, Turkey, 4 Department of Pathology,
Operating Characteristic (ROC) curve of 0.88, 0.88 and 0.87, respectively. Laboratory Medicine Program, University Health Network, Toronto,
PTC patients with low DNA methylation levels of two or three markers Canada, 5 Department of Laboratory Medicine & Pathobiology,
more frequently had tall cell variants, extrathyroidal extension, lymph node University of Toronto, Canada, 6 Endocrine Oncology Site, The
metastasis, BRAF V600E mutations, and high recurrence risk than those Princess Margaret Cancer Centre, Toronto, Canada
with low levels of zero or one methylation marker. All patients who devel-
oped disease recurrence had low DNA methylation levels for three markers. Background & Objectives:The role of autoimmunity-related tissue in-
Conclusion: DNA methylation levels of three markers can be useful for jury in development of thyroid cancer remains an area of interest.
differentiating PTC from non-malignant follicular thyroid lesions, and for Evidence suggests that patients with Graves’ disease may have an in-
selecting high-recurrence risk PTC patients. creased risk for differentiated thyroid cancer. Multicenter studies are
needed to gain insights into the correlates of papillary thyroid carcinoma
Supported by a grant (HI16C2013) from the Korean Health Technology (PTC) identified in this particular group of patients. This study investi-
R&D Project and a grant (2017R1D1A1B03029597) from the Basic gated the prevalance of PTC and synchronous thyroid nodules in thyroid-
Science Research Program of Korea. ectomy specimens of Graves’ patients originating from an endemic goiter
region.
Methods: A retrospective review of Institutional pathology records at two
PS-22-013 tertiary-care centers identified 173 surgically treated Graves’ patients.
Increased oxyphil cell ratio, parathyroid gland volume and weight Patients were grouped as GN when coexistent nodular thyroid was noted,
correlate with the localisation of parathyroid adenoma on and those with no synchronous thyroid nodules were grouped as G. The
Technetium-99m MIBI scintigraphy scan prevalence of PTC and its histopathological correlates, and demographic
E.T. Durmuş1, M. Kefeli2, D. Bayçelebi2, A. Atmaca1, R. Çolak1, C. characteristics were recorded. These were compared between groups GN
Polat3, O. Mete4,5,6 and G.
1
Department of Endocrinology and Metabolism, Ondokuz Mayis Results: Ninety-five and seventy-eight patients were assigned to groups
University, Samsun, Turkey, 2 Ondokuz Mayıs University, Department GN and G. The mean age was significantly higher in group GN when
of Pathology, Turkey, 3 Department of General Surgery, Ondokuz Mayis compared to group G. The overall frequency of PTC was 31% (53/173).
University, Samsun, Turkey, 4 Department of Pathology, Laboratory The rates of PTC were 45% (43/95) and 13% (10/78) in groups GN and
Medicine Program, University Health Network, Toronto, Canada, G(p<0.0001). Papillary microcarcinomas accounted for around 80% of
5
Department of Laboratory Medicine & Pathobiology, University of all PTCs in both groups. Group G was enriched in BRAF-like tumours
Toronto, Canada, 6 Endocrine Oncology Site, The Princess Margaret whereas group GN had a balanced RAS- and BRAF-like tumours.
Cancer Centre, Toronto, Canada Conclusion: This series underscored most PTCs encountered in patients with
Graves’ disease are papillary microcarcinomas. Furthermore, the biology and
Background & Objectives: Technetium-99m MIBI Parathyroid prevalence of PTC vary depending on the presence of underlying nodular
Scintigraphy (Tc-Scan) has been used to localize abnormal glands in thyroid tissue.
Virchows Arch

PS-22-015 occurs occasionally in these biologically indolent tumours. The impact of

IGF-1 splice variants' expression in adrenal gland neoplasms - pos- tumour size as risk factor of metastasis remain unknown. Therefore, this
sible role in adrenal tumourigenesis study aimed to determine impact of including sub-centimeter lesions un-
G. Kyriakopoulos1, N. Nasiri-Ansari1, A. Angelousi2, A. Philippou3, A. der NIFTP entity on the reported prevalence of metastasis attributed to
Karapanagioti1, G. Zografos4, C. Aggeli4, T. Choreftaki5, D. Tiniakos6,7, NIFTP based on systemic review followed by meta-analysis.
D. Rontogianni8, G. Dimitriadis9, G. Kaltsas10, A.G. Papavassiliou1, E. Methods: The literature search was conducted using Pubmed/
Kassi1,2 MEDLINE databases searching for original NIFTP articles up until
1
Department of Biological Chemistry, Medical School, National and Feb 2019. A proportion meta-analysis calculation was used to ob-
Kapodistrian University of Athens, Greece, 2 1st Department of Internal tain the pooled prevalence of the adverse event (lymph node and/or
Medicine, Laiko University Hospital, National and Kapodistrian distal metastasis) in lesion size subgroups (sub-centimeter, centime-
University of Athens Medical School, Greece, 3 Department of ter and larger, or both). Using the random-effects model to pool
Physiology, Medical School, National and Kapodistrian University of weighted proportions were reported with stander error (SE), and
Athens, Greece, 4 3rd Department of Surgery, General Hospital of 95% confidence intervals (CI). The significant the heterogeneity
Athens "G. Gennimatas", Greece, 5 Department of Pathology, General was defined as an I2 >50%.
Hospital of Athens "G. Gennimatas", Greece, 6 Department of Pathology, Results: Ultimately, 16 studies were included for meta-analyses, 44/1361
Aretaieion Hospital, National and Kapodistrian University of Athens (3.2%) NIFTPs had adverse events. In 8 studies included sub-centimeter
Medical School, Greece, 7 Institute of Cellular Medicine, Newcastle lesions, 35/800 NIFTPs associated with metastasis compromised 2% [CI
University, United Kingdom, 8 Department of Pathology, Evaggelismos 0%-6%] pooled prevalence with significant heterogeneity (I2 80%,
Hospital, Athens, Greece, 9 Division of Translational and Experimental p<0.001). 6 studies excluded sub-centimeter lesions, 8 /494 NIFTPs with
Medicine-Metabolic and Vascular Health, Warwick Medical School, the adverse events with negligible pooled prevalence of metastasis [CI
University of Warwick, Coventry, United Kingdom, 10 1st Department 0%-2%] without the heterogeneity (I2 49.81%, p=0.06). Two studies
of Propaedeutic Internal Medicine, Laiko University Hospital, National evaluated only sub-centimeter lesions, 1/60 lesions had metastasis, with
and Kapodistrian University of Athens Medical School, Greece negligible pooled prevalence [CI 0%-3%].
Conclusion: Among the majority of “indolent” NIFTP, lymph
Background & Objectives: IGF-1Ea, IGF-1Eb and IGF-1Ec isoforms node/distal metastasis occurs occasionally at 3.2 %. The pooled preva-
are differentially regulated in neoplasms. Moreover IGF-1Ec and IGF- lence of metastasis was negligible in the studies excluded sub-centimeter
1Eb overexpression has been positively associated with cell survival and lesions compared to 2% in the others included sub-centimeter lesions.
proliferation in tumourigenesis. We aimed to examine the expression of Further risk factors studies should be conducted to evaluate the utility
IGF-1 isoforms in human adrenocortical carcinomas (ACCs), adrenocor- of establishing size criteria to predict a higher possibility of biologically
tical adenomas (ACAs), pheochromocytomas(Pheo) and compare to nor- aggressive NIFTP.
mal adrenal gland(NAG). Additionally, we investigated the role of IGF1-
Ec and IGF1-Eb peptides in ACC cells proliferation/migration.
Methods: The mRNA and protein levels of IGF-1 isoforms were evalu- PS-22-017
ated by qPCR and immunohistochemistry respectively. SW-13, H295R PD-L1 expression in normal endocrine tissue
cells were incubated with IGF-1Ec and IGF-1Eb peptides. Cell prolifer- T. Neuman1, M. Kagan1, R. Dresner-Pollak1, R. Pollack1
1
ation and scratching assays were performed. The Hebrew University - Hadassah Medical Center, Jerusalem, Israel
Results: IGF-1 isoforms mRNA levels were increased in adrenal cortex
neoplasms compared to medulla. Additionally, the mRNA levels of IGF- Background & Objectives: Immune checkpoint inhibitor (ICI) therapy,
1Ec and IGF-1Eb were significantly higher in ACCs as compared to including cytotoxic T-lymphocyte-associated protein 4 (CLTA-4) and
ACAs. Immunohistochemistry revealed that 100%of ACCs, 73.3%of programmed cell death 1 (PD-1) inhibitors, is revolutionizing cancer
ACAs and 70%of NAGs expressed IGF-1Ec, 67% of ACCs, 25% of treatment. However, these agents are associated with immune-related
ACAs and 75% of NAGs expressed IGF-1Eb. IGF-1Ea was detected adverse events (irAEs), most commonly endocrine-related.
only in ACCs (58%) and ACAs (66%). IGF-1Eb protein expression Hypophysitis, thyroid dysfunction, insulin-deficient diabetes mellitus
levels were higher while IGF-1Ec expression levels were reduced in and primary adrenal insufficiency have been reported as irAEs due to
NAGs compared to ACCs. No IGF-1 isoforms were detected in the ICI therapy. The reasons why endocrine irAEs are so common in ICI
Pheo. A borderline negative correlation between IGF-1Eb protein levels treatments are unkonwn. In this study, we evaluated patterns of pro-
and IGF-1Eb/IGF-1Ea ratio with Ki-67 was observed in ACCs. grammed cell death ligand 1 (PD-L1) expression in normal endocrine
Incubation of SW-13 and H295R cells with IGF-1Ec resulted in a signif- tissues to determine whether increased expression may explain the predi-
icant increased in cell proliferation and migration. lection of endocrinopathies in patients treated with PD-1 inhibitors.
Conclusion: Expression of IGF-1Ec is related to malignant behaviour of Methods: Immunohistochemical (IHC) analysis using the Ventana 22C3
adrenal neoplasms. IGF-1Ec appears to play a causative role while higher PD-L1 IHC platform was performed on normal thyroid, parathyroid,
expression of IGF-Eb may have a protective effect in ACC adrenal and pancreatic FFPE endocrine tissue samples stored in our hos-
tumourigenesis. pital pathology tissue archive. Pituitary tissue samples were obtained
from non-functioning pituitary adenomas.
Results: Five samples from each organ including pituitary, thyroid, para-
PS-22-016 thyroid, adrenal and pancreas were examined.
May lesion size impact recognition of biologically aggressive non- Focal membranous PD-L1 positivity was noted in the pituitary adenomas
invasive follicular thyroid neoplasm with papillary-like nuclear fea- consistent with previous data, but was negative in normal thyroid, para-
tures? Meta-analysis thyroid, adrenal and pancreatic tissues.
I. Laklouk1, R. Fazeli1, S. Cerda1, R. Gedik1 Conclusion: The majority of normal endocrine tissues do not demon-
1
Boston University Medical Center, USA strate increased PD-L1 expression.
Our preliminary data so far does not support the hypothesis that increased
Background & Objectives: Non-invasive follicular thyroid neoplasm PD-L1 expression in endocrine tissues is associated with endocrine irAEs
with papillary-like nuclear features (NIFTP) represents a special cohort following anti PD-1 therapy. The increased predilection of
of encapsulated thyroid neoplasm that has been unanimously distinct as endocrinopathies in patients treated with anti PD-1 inhibitors seems to
biologically indolent neoplasm. Lymph node/distal metastasis, however, be via alternate pathways.
 Virchows Arch

PS-22-018 However, the impact of INSM1 in the biology of MTCs remains

The use of FTIR spectroscopy for search of a biomolecular pattern largely unknown. This study aimed to investigate the biological
differentiating adrenal gland tumours significance of INSM1 expression in MTCs by comparing its
M. Ulatowska-Białas1, J. Dudała2, K. Okoń1 expression profile with conventional clinicopathological
1
Jagiellonian University, Collegium Medicum, Chair of parameters.
Pathomorphology, Poland, 2 AGH University of Science and Methods: Thirty-six MTCs were stained with INSM1 (Clone
Technology, Faculty of Physics and Applied Computer Science, Poland A-8, 1:200 dilution, 37°C, 30 min. incubation, Santa Cruz) and
assessed using an automated image analysis nuclear algorithm.
Background & Objectives: In recent years, there has been a grow- A histoscore (H-score) (max: 300) was given to each tumour
ing interest in the FTIR microspectroscopy as a complementary based on an integrated formula [H-score = 1×(1+ cells%) +
diagnostic method. Investigations are carried out to find biomo- 2×(2+cells%) + 3×(3+ cells%)]. The H-scores were correlated
lecular markers of pathological states, including neoplastic with clinicopathological parameters including age, gender, tu-
changes. For method validation the wide-range population stud- mour size and multifocality, angioinvasion, lymphatic invasion,
ies should be done. In case of rare disease it would be conve- perineural invasion, extrathyroidal extension, nodal metastasis,
nient to use the formalin-fixed paraffin-embedded (FFPE) tissue and tumour stage.
samples. In presented study we tried to explore the possibilities Results: All MTCs except one with a widely invasive growth were
of using the archival deparafinized cortical part of adrenal gland INSM1 positive. The mean H-score was 136.75±59.08 (range: 0-
tissue samples. 251.24). Among clinicopathological variables, angioinvasion (mean:
Methods: An archival FFPE tissue samples (5 normal adrenal 94.8±53.3), extrathyroidal extension (86.4±43.3), and tumour
cortex - N, 8 adrenocortical adenoma - ACA, 8 adrenocortical multifocality (116.5±51.5) were associated with significantly reduced
carcinoma - ACC) were used (approval number KBET/113/B/ H-scores (p=0.001, p=0.038, p=0.039, respectively). While H-scores
2014). The Fourier Transformed Infrared Spectroscopy (FTIR) were decreased in tumours with advanced stage, this observation did
was applied in the measurements. To avoid the interference from not yield a statistical significance (p=0.067). There was no correlation
paraffin on IR spectra, samples were de-waxed under standard with INSM1 and other variables.
local histological protocol. The averaged spectra for each group Conclusion: Reduced nuclear INSM1 expression in a subset of
were used for general comparison. The spectra second derivative MTCs with adverse histological features (angioinvasion and
were used to determine the main absorption bands as well as to extrathyroidal extension) maybe due to cellular mechanisms that
perform the semi-quantitative analysis of the biomolecular com- result in disruption of embryonic transcription of INSM1-
position. The non-parametric Mann-Whitney U test was used for mediated neuroendocrine differentiation in these tumours.
statistical analysis. Further translational studies are required to explore the underly-
Results: The analysis was based on the “fingerprints” spectral ing biology of INSM1 in neuroendocrine tumourigenesis.
region 1710 – 900 cm-1. The main absorption bans were find
at around ~1643 cm -1, 1537 cm -1, 1454 cm -1, 1394 cm -1, This study has received financial support from Recep Tayyip Erdoğan
1310 cm-1, 1237 cm-1 as well as between 1180 and 1140 cm-1. University Scientific Research Support Fund.
The differences in the position of the dominant absorption band
within the 1700-1600 cm -1 spectral range of amide I were find.
The biggest difference were found within the region 1135 - PS-22-020
980 cm -1 (attributed to carbohydrates and nucleic acids). Reassessing primary thyroid tumours according to the new WHO
Conclusion: The presented results show that it is possible to com- classification: A five-year retrospective study
pare IR spectra of the deparaffinised samples from adrenal gland S. Tzorakoleftheraki 1 , C. Poulios 1 , S. Arelaki 1 , O. Kazarli 1 , G.
tissues but the differences are not so evident. The spectral region Karayannopoulou1
1
which could be taken into differentiation procedure is connected Pathology Department, Faculty of Medicine, Aristotle University of
with absorption band attributed to DNA (1237 cm -1) and the Thessaloniki, Greece
whole massif related mainly with carbohydrates between 1130
and 980 cm -1. Background & Objectives: The latest WHO classification intro-
duced new entities regarding follicular neoplasms with low risk
of recurrence or metastasis. The scope of the present study was
PS-22-019 to reevaluate archival cases of primary thyroid tumours accord-
Biologic significance of Insulinoma-associated protein 1 (INSM1) ex- ing to this classification, with emphasis on diagnoses that could
pression in medullary thyroid carcinoma modify the follow-up of the patients.
O. Semerci1, H. Gucer1, D. Baycelebi2, M. Kefeli2, O. Mete3,4,5 Methods: We retrieved cases of primary thyroid tumours from
1
Recep Tayyip Erdogan University, Department of Pathology, Turkey, the archives of the Department of Pathology, Aristotle
2
Ondokuz Mayıs University, Department of Pathology, Turkey, University of Thessaloniki, collecting a period of five years
3
Department of Pathology, Laboratory Medicine Program, University (2013-2017) prior to the incorporation of the latest WHO clas-
Health Network, Toronto, Canada, 4 Department of Laboratory sification. We recorded the diagnosis along with complete histo-
Medicine & Pathobiology, University of Toronto, Canada, 5 Endocrine logical data, including tumour size, presence of full capsule
Oncology Site, The Princess Margaret Cancer Centre, Toronto, Canada (with or without invasion), tumour architecture, cellular and nu-
clear features. The aim was to identify all the cases that would
Background & Objectives: Clonal tumour progression can lead have a different diagnosis according to the new classification.
disruption of cellular differentiation in malignancy. INSM1is a Results: A total of 518 cases of primary thyroid tumours were
transcription factor implicated in neuroendocrine differentiation retrieved. We disclosed up to 15 cases that had a different di-
and has been shown to be positive in various neuroendocrine agnosis. These cases were encapsulated neoplasms, mostly with
neoplasms including medullary thyroid carcinomas (MTCs). follicular architecture. The updated diagnoses included well-
Virchows Arch

differentiated tumour of uncertain malignant potential, non- Background & Objectives: Primary hyperparathyroidism (PHPT)
invasive follicular thyroid neoplasm with papillary nuclear fea- is often accompanied by thyroid pathologies. Nowadays, there
tures and minimally-invasive follicular carcinoma. is an increased rate of performing minimally invasive parathy-
Conclusion: The incorporation of new classification systems re- roidectomy, thus thyroid diseases can be missed.
flects the ongoing changes in patient management, which in this Methods: We performed a retrospective histopathological study
case is based on the histopathological report, making it essential on PHPT cases diagnosed between 2011 and 2018 at the
for pathologists and clinicians to be up-to-date with the latest Emergency County Hospital Timisoara, Romania. We aimed to
WHO classification. assess the rate of concurrent PHPT and thyroid diseases.
Results: We identified 66 cases of PHPT (54 women and 12
men, mean age 54.16) diagnosed as: 39 adenomas, 1 carcinoma,
PS-22-021 25 nodular hyperplasia, 1 nodular hyperplasia associated with
PD-1 and PD-L1 expression in pulmonary carcinoid tumours parathyromatosis. 30/66 (45.45%) cases presented associated
T. Vesterinen1, T. Kuopio2, M. Ahtiainen3, A. Knuuttila4, K. Salmenkivi1, thyroid pathologies: 17/66 (25.75%) nodular and diffuse goiters,
H. Mustonen5, J. Arola1, C. Haglund5 1/66 Basedow disease (1.51%), 8/66 (12.12%) carcinomas (1
1
HUSLAB, Department of Pathology, University of Helsinki and isolated papillary microcarcinoma, 6 papillary microcarcinomas
Helsinki University Hospital, Finland, 2 Department of Biological and associated with nodular goiter and 1 papillary carcinoma – fol-
Environmental Science, University of Jyväskylä and Department of licular variant), 2/66 (3.03%) follicular adenomas and 2/66
Pathology, Central Finland Health Care District, Finland, 3 Department (3.03%) autoimmune lymphocytic thyroiditis.
of Education and Research, Central Finland Central Hospital, Finland, Conclusion: The association between PHPT and thyroid patholo-
4
Department of Pulmonary Medicine, Heart and Lung Center, and gies is not uncommon in our study group. Therefore, in the case
Cancer Center, University of Helsinki and Helsinki University Hospital, of minimally invasive parathyroidectomy, the possibility of
Finland, 5 Department of Surgery, University of Helsinki and Helsinki coexisting thyroid pathology should be considered and steps to-
University Hospital, Finland wards its diagnosis must be taken.

Background & Objectives: Pulmonary carcinoid (PC) tumours are

rare tumours that account for approximately 1% of all lung can- PS-22-023
cers. The primary treatment option is surgery, while there is no Predictive factors for recurrence in poorly differentiated thyroid
standard treatment for metastatic disease. As the number of PCs carcinomas
diagnosed yearly is increasing, there is a need to establish novel E.-.A. Zahan1, A. Nechifor-Boilă2, D. Piciu3, A. Borda4
1
therapeutic options for these patients. This study aimed to in- Department of Histology, University of Medicine, Pharmacy, Science
vestigate programmed death protein 1 (PD-1) and programmed and Technology of Targu Mures, Romania, 2 Department of Histology,
death ligand 1 (PD-L1) in PC tumours since blocking of the PD- UMFST Târgu Mureş, Romania, 3 Department of Nuclear Medicine, "Ion
1/PD-L1 pathway is a promising therapeutic option in various Chiricuţă" Institute of Oncology, Cluj-Napoca, Romania, 4 Department of
other malignancies. Histology, UMFST Targu-Mures, Romania
Methods: A total of 125 consecutive PC patients operated on in the
Helsinki University Hospital between 1990 and 2013 were included. Background & Objectives: Poorly differentiated thyroid carcinoma
Patient records were retrospectively reviewed. Expression of PD-1 and (PDTC) is a rare and aggressive tumour. The aim of our study was
PD-L1 was evaluated immunohistochemically and correlated with clini- to assess the predictive factors for persistent-disease and recur-
cal parameters. rence of PDTC in our Institution.
Results: After re-evaluation of the tumours, 93 (74%) were clas- Methods: We performed a retrospective study on 34 PDTC cases
sified as typical carcinoid (TC) and 32 (26%) as atypical carci- from the Department of Pathology, Targu-Mureş Emergency
noid (AC) tumours. Expression of PD-1 was detected in 7% of County Hospital between 1990-2015. Pathological data were re-
the tumours. PD-L1 expression was detected in 8% of TC tu- trieved from database registers and pathological reports, whereas
mours; all AC tumours were PD-L1 negative. PD-L1 expression follow-up data were obtained from the Department of Nuclear
was associated with mediastinal lymph node metastasis at the Medicine, “Ion Chiricuţă” Institute of Oncology, Cluj-Napoca.
time of diagnosis (P=0.014). Neither PD-1 nor PD-L1 expres- Results: In our study the prevalence of PDTC was 3,9% (34 PDTCs/869
sion was associated with survival. thyroid cancers). All patients were treated by total thyroidectomy follow-
Conclusion: Our data suggest that PD-1/PD-L1 is expressed in 7- ed by 131I ablation. The mean follow-up period was 75 months (available
8% of PC tumours. PD-L1 expression seems to be associated with data for 25 cases). At the last clinical assessment, the disease-free surviv-
increased malignancy. Thus, targeting of the PD-1/PD-L1 pathway al-rate at 5 years was 83% and the 5-year recurrence-free survival was
may offer a treatment option for a small subset of PC patients. 48.3% By univariate and multivariate analysis, following risk factors
were predictive for persistent disease and recurrence: age (older than 55
years-old) (OR) 5.97, p-0.001), tumour size ≥ 4mm (OR 9.97, p-0.001),
PS-22-022 extrathyroid extension (OR 12.66 p<0.005) and lymph node involvement
Association of thyroid pathology to primary hyperparathyroidism (OR 17.66 p<0.005). This parameter influencing the disease-free survival
requires complex investigations prior to treatment rate. Six (28%) patients developed metastases (lung and bones), during
O. Vita1, A. Văduva1, R. Cornea1,2, C. Lăzureanu1,2, A. Mureșan1,2, G. the follow-up period.
Oprișan2, M. Iacob2, E.G. Olteanu1, I. Golu3, M. Cornianu1,2 Conclusion: PDTCs is an aggressive tumour, with high rates of
1
Department of Pathology, "Victor Babeș" University of Medicine and persistent disease and recurrence. Age (older than 55 years-old),
Pharmacy, Timișoara, Romania, 2 Department of Pathology, Emergency extrathyroid extension, lymph node involvement and tumour size ≥
County Hospital Timișoara, Romania, 3 Department of Endocrinology, 4 mm were found to be risk factors for recurrence. Careful clinical
"Victor Babeș" University of Medicine and Pharmacy, Timișoara, monitoring of patients with these factors for early detection of
Romania metastasis is necessary.
 Virchows Arch

Conclusion: The most common disease in this collection was syph-

Wednesday, 11 September 2019, 09:30 - 10:30, Agora 3
ilis. Some other STDs were present so as those related to HPV
PS-23 | History of Pathology
infection. The morphology of these diseases seems to be compa-
rable to the modern one. The absence of preventive healthcare and
PS-23-001 of modern therapies often caused death even if these diseases were
Professor Leo Taussig - an underestimated pioneer of complex inves- preventable and treatable.
tigation of cerebrospinal fluid
J. Dušková1, O. Sobek2
1
1st Faculty of Medicine, Charles University, Prague, Czech Republic, PS-23-003
2
Topelex, s.r.o., Czech Republic Pathological findings of the 1918-1920 Spanish influenza from the
autopsy report of the University of Turin
Background & Objectives:To trace back the history of CSF fluid knowl- L. Ferrari1
1
edge and investigation. Division of Pathology Cardinal Massaia Hospital Asti, Italy
Methods: Comprehensive review of international and national da-
tabases and archive materials. During the studies of cognition and Background & Objectives: The ancient catalogs kept at the
the function of CSF, a large, 440 page, comprehensive monograph Pathology Department of Turin report autopsies of all deceased
by Prof. Leo Taussig (1884 – 1944) published in Czech in 1926, in city hospitals. These reports describe the most relevant patho-
was discovered. Its content represents a valuable resource and a logical findings and the final cause of death. An archive search
basis for the tradition of complex CSF investigation still respected was carried out to investigate the pathological findings of the
today. Spanish flu from autopsy descriptions.
Professor Taussig was a teacher of the Czech part of Charles University. Methods: The cases with the diagnosis of "flu bronchopneumonia" were
Results: Professor Taussig was an excellent specialist, healthcare selected. Cases of " hemorrhagic bronchopneumonia" have also been
organizer and chess player. He was unfortunately also Jewish. That selected since 1918. They were probably also due to the flu, although
is why his fate unfolded in the tragic times of the Protectorate of the initial censorship prevented mentioning it directly.
Bohemia and Moravia in the same way as the fate of the Jewish Results: The first case of flu was that of a 23-year-old male who
professor of the German part of Charles University in Prague, died on 24th November 1918. There was a first pandemic wave
Oscar Fischer - the author of priority articles on dementia later between October 1918 and April 1919. Subsequently there are no
called Alzheimer's. Neither man survived the Holocaust and their reported cases until January 1920 which was the month with the
scientific work remained unfinished. greatest number of death, 16 in all. Among them only 4 people
Conclusion: Leo Taussig's outstanding work printed in Czech re- were over 40 years. The last reported case was that of a 22-year-
mains unknown internationally. Cultivation of national culture and old female who died on 7th February 1920.The reports describe a
language should run in parallel with communicating outstanding hemorrhagic bronchopneumonia, splenic reactive hyperplasia and
works to the international scientific community. The problem of blood congestion of kidney and liver. The report also show that
racial intolerance has regrettably not disappeared. Scientific and there was no particular concern for post-mortem infectivity, in fact
educational careers discontinued in such an untimely way serve as an autopsy was performed during the autoptic technique lessons.
a warning sign of losses to the scientific community. Conclusion: The autopsy reports of the University of Turin confirm
the prevalence of the Spanish flu in young people and the temporal
distributions of deaths reflects the pandemic trend. The patholog-
PS-23-002 ical findings are comparable to those described in the literature
50 shades of H&E: sexually transmitted diseases (STDs) in the pa- often referable to bacterial pneumonia following viral infection.
thology collection of Turin
L. Ferrari1
1
Division of Pathology Cardinal Massaia Hospital Asti, Italy PS-23-004
Necropsy reports and anatomo-pathological observations from the
Background & Objectives: The Pathology Collection of Turin archives of the grand ducal Medici family of Florence (16th-18th
houses around 300 wet specimens dating back to end of XIX century)
century and beginning of the XX century. The Sexually R. Gaeta1, V. Giuffra1
Transmitted Diseases were really common in Turin at the time 1
University of Pisa, Italy
shown on the autopsy reports. The most common disease was
surely syphilis both congenital and acquired. However HPV relat- Background & Objectives: During the Renaissance and Early
ed infections were also widespread. The wet specimens of STDs Modern Age, dissection began to be practiced for medico-legal
cases in the Collection were selected to investigate these old dis- purposes, in order to investigate the causes of death. In particular,
eases epidemiologically and morphologically. during the 15th century evidences of autopsies performed by doc-
Methods: The choice of the cases was based on the original diagnosis tors on their private patients emerge. These dissections were re-
reported on the label. The most representative cases were sampled by quested by those families who can afford the expenses, in order to
conservative approach and a diagnostic re-evaluation with modern search the possible presence of hereditary diseases and to predis-
techiniques was performed. pose a prevention and cure. The diffusion of this practice is
Results: There are a total of 29 cases of STDs: 24 cases of tertiary attested also by the work of Antonio Benivieni (1443-1502),
syphilis, 4 cases related to HPV infections and a case of blenorrhagia. who is considered a pioneer of the pathological anatomy.
In the sampled cases the morphology allows the diagnostic re-evaluation. Methods: The extremely rich documentary archives of the Medici
Immunohistochemistry showed incostant results but thanks to the posi- family, one of the most important family of the Italian Renaissance,
tivity for Cytokeratin MNF 116 and p63 a case of vulvar "adenocarcino- report several description of necropsies carried out on the bodies of
ma" was re-evaluated as squamous carcinoma, probably related to HPV the members of the Grand Ducal family. It was possible to analyse
infection. the original documents and, in some cases, to compare them with
Virchows Arch

the skeletal remains studied during the exploration of the Medici distinguished as a separate entity and properly appreciated. Teratology
tombs in the Basilica of San Lorenzo in Florence. as a term was introduced by Etienne Geoffroy Saint-Hilaire (1772-1844)
Results: The analysis of the autoptic reports offers important direct and Isidore Geoffroy Saint-Hilaire (1805–1861) in the 19th century, but
information on the autopsy practices performed by court surgeons first images of deformed fetuses and newborns date around 15.000 years
of the members of an aristocratic class in a period comprised back. Hippocrates was one of the first trying to find the mechanisms and
between the 16th and the first half of the 18th century, and allows causes of different deformations. Despite all this long history the first
in some cases also to propose a retrospective diagnosis on the noted autopsy concluded with a post mortem report dates from 1533.
diseases that afflicted the Medici. For several centuries it was rather performed as a curiosity than real
Conclusion: The analysis of the documents relating to the autopsy anatomical and pathological procedure for medical and scientific re-
investigations proves to be of great interest and importance. These search. Even today with subspecialties as molecular or neuropathological
archives are in fact a very valuable source of information about the autopsy it is still put aside, though the demands to perform it, especially in
state of health of past populations and reveal which diseases were most rare cases, are extremely high.
present and how they were treated. Methods: We performed critical review of the available articles and re-
searches published in the databases (PubMed, Researchgate and
Academia.edu) focusing on perinatal autopsies with reported deforma-
PS-23-005 tions and malformations dating form the ancient to present times. The
Exhumation and anthropological study of the skeletal remains attrib- literature was confronted with personal experience of researchers from
uted to Liutprand, King of the Longobards (690 ca AD-744 AD) our team.
R. Gaeta1, S. Minozzi1, A. Fornaciari3, V. Giuffra1, G. Riccomi1, G. Results: The vast range of variations that can be found during the
Fornaciari1 perinatal autopsy with deformations requires skills and knowledge
1
University of Pisa, Italy, 2 Division of Paleopathology, Department of far from the usual. In some cases the procedures are performed on
Translational Research and New Technologies in Medicine and Surgery, such scale that magnifier may be applied. The post mortem reports
University of Pisa, Italy are connected with perinatal counselling, but what is more important
with consecutive decisions about parenting. Therefore it is even
Background & Objectives: Liutprand, one of the greatest more appropriate to quote "Hic est locus ubi mors gaudet succurrere
Longobard sovereign, was born in the early 90s of the 7th century vitae" - this is the place (or case) where death gladly helps the
and died in 744 at the age of about 55 years. According to the living. What is more - it helps those who just might have the chance
Historia Longobardorum of Paolo Diacono, he was King of Italy to be born in the nearest future.
from 712 to 744. Conclusion: The teratological autopsy should be distinguished as a
Methods: We performed the exhumation and the anthropological study separate subtype of post mortem examination with full stress on the
on the skeletal remains attributed to Liutprand in the Church of San Pietro technical skill demands and proper preparation to it.
in Ciel d'oro (Pavia, Italy). We selected bone fragments and two teeth in
order to make imaging studies (CT and RX), 14C dating, chemical and
molecular analyses. PS-23-007
Results: Anthropological examination highlighted the presence of Unexpected heart dwellers
bones attributable to at least three individuals. Most of the remains R. Henriques de Gouveia1, T. Ferreira2, L. Carvalho3
1
belonged to a robust male individual with an age to death between INMLCF & FMUC & CHLO, Portugal, 2 FMUC, Portugal, 3 FMUC &
40 and 50 years. We found a left tibia with the diaphysis complete- CHUC, Portugal
ly enlarged due to a severe form of osteomyelitis. Bone repair is
evident and the presence of a circular depression with a diameter Background & Objectives: Heart involvement by Echinoccocus is rare
of about 10 mm could represent the trace left by a pointed object (0.02-2% or 0.5-3% in the worldwide literature), although – when present –
that caused the perforation of the bone and the subsequent infec- may be responsible for relevant morbidity or mortality (namely arrhyth-
tion. 14C dating provide a range from 430 to 640 for the first mias, anaphylactic shock, sudden death). The authors present a specimen
subject, 600-770 for the second and 530-670 for the last male. from an historical museum.
Isotopic data show a rather high nutritional status for the time. Methods: A liquid-fixed heart specimen from a 19th century European
Conclusion: Currently it is not possible to define the identity of Pathology Museum was analysed.
the three individuals for lack of archaeological data and for the Results: Multiple Hydatid Cysts were observed, involving / damaging
fragmentary nature of the bones. The age of the subjects, the various cardiac structures.
robust constitution and the nutritional data suggest a belonging Conclusion:This presentation testify a type of zoonotic pathology in this
to a middle-high social class devoted to war activity. Future mo- European country in the 19th century and highlight the teaching mission
lecular studies may reveal a degree of kinship between the indi- of University Museums, since with globalization and interexchange pro-
viduals and clarify the identity of the subjects. grams, medical students/residents/young doctors may face diverse dis-
ease contexts – in their home country or abroad –, namely unexpected
parasitosis.
PS-23-006
The short history of non-existing procedure - teratological autopsy
J. Gulczyński1, S. Goertz2, W. Grajkowska3, E. Izycka-Swieszewska1,2 PS-23-008
1
Department of Pathology and Neuropathology, Medical University of History of teaching pathological anatomy (pathology) at Moscow
Gdansk, Poland, 2 Pathomorphology Department Copernicus Hospital, State University
Gdansk, Poland, 3 Pathology Department The Children's Memorial Health P. Mailkov1, N. Danilova1, N. Oleynikova1, N. Gaifullin1, I. Mikhailov1
1
Institute, Warsaw, Poland Lomonosov Moscow State University, Russia

Background & Objectives: The objective was to describe the type of Background & Objectives: Pathology is a fundamental discipline that
autopsy, which though performed since ages, never had been has traditionally been the bridge between science and medicine.
 Virchows Arch

Pathology teaching is important discipline of the training of qualified MD examination, and CT scanning. A left abdominal stone was removed by
specialists which is traditionally carried out in the departments of pathol- videoendoscopy and investigated with binocular stereomicroscopy,
ogy of the Medical Faculties of classical Universities. microcomputed tomography, scanning electron microscopy with micro-
Methods: The collection of history data was carried out by archival analysis, and X-ray diffraction analysis.
search. Results: The ovoidal mass measured 22x16x15 mm. External surface
Results: The Moscow University was founded in 1755. Teaching showed small superficial spherical buds, whereas internal structure detail
of pathology began in 1769 (Veniaminov P.D.). Further develop- revealed a central nucleus of sharp-edged crystals and concentric lamina-
ment Pathology in Russia is associated with Polunin A.I., Klein tions of similar density values. Chemical elements were: C, O, N, Ca, P,
I.F., Abrikosov A.I. In 1930, Medical Faculty was transformed K, S, Cl, Na with different distribution within inner and outer surfaces of
into the 1stMoscow Medical Institute and to which university the stone. Compositional analysis revealed calcium oxalate monohydrate
clinical campus builded in 1897 was transferred. Medical educa- (whewellite) (90%) and calcium phosphate (hydroxylapatite) (10%).
tion in Moscow University was restored 62 years later (1992). Conclusion: The stone composition supports the hypothesis of
Currently, a course of pathological anatomy is taught at the high animal protein intake by the subject, confirming that he
University Clinic on basis of Clinical Pathology Department. belonged to high social class. The co-existence of significant den-
Conclusion: The University Clinic has qualified specialists and tal pathologies, without major arthritic changes confirmed a life
modern equipment. Biopsy and surgical materials, modern histo- free from extensive labor. The cause of death could be related to
logical, histochemical, immunohistochemical, molecular, genetic, infectious complications of renal urolithiasis and hydronephrosis.
ultrastructural methods are widely used both for education and
science purposes which ensures the implementation of the unity
of education, science and clinical practice. Wednesday, 11 September 2019, 09:30 - 10:30, Agora 3
PS-24 | Pathology in Favour of Developing Countries

PS-23-009
PS-24-001
The history of research of placenta
Comparison of HER2 status in breast cancer using fluorescent in situ
T. Pavlova1, A. Selivanova1, A. Kaplin1, A. Nesterov1, L. Zemlianskaia1
1 hybridisation and immunohistochemistry at National Hospital
Belgorod State University, Russia
Abuja, Nigeria - a case for alternate testing in developing countries
A.N. Ado Wanka1, S. Amin1, P. Taniere2, P. Jibrin1, A. Shaaban2
Background & Objectives: The history of research of placenta is impor- 1
National Hospital Abuja, Nigeria, 2 Queen Elizabeth Hospital,
tant aspect in obstetrics
Birmingham, United Kingdom
Methods: Work with archive, materials, textbooks and monographs
Results: The first mention of placenta was revealed in archives of
Background & Objectives: Breast cancer patients that are positive
Egyptian pharaoh Amenhotep IV. T. Langhans explored histological
for HER2 will benefit from targeted therapy. Most centres in
structure of placenta and the microscopic period of placenta’s re-
Nigeria utilise only immunohistochemistry (IHC) in determining
search was begun. Active research of this organ was in the end of
HER2 status, as it is cheaper, quicker and more widely available.
XIX century (Schatz F., V. Becker Bar P., Wilson T.). The ultrami-
Cases that are IHC equivocal present a treatment dilemma, as
croscopic period in the research of placenta begun in the second part
there is currently no centre in the country that provides alternate
of XX century. The separate science called “placentology’ was
test to assess these tumours. The objective is to compare HER2
formed.
expression by IHC with HER2 gene amplification by fluorescence
Conclusion: The study of placenta allows to make a basis for correct
ISH (FISH).
diagnosis, correction and treatment of pathological conditions in obstet-
Methods: Clinical information was obtained from request form.
rics for preservation.
Haematoxylin and Eosin stained slides were evaluated for histologic
type and tumour grade. Dual probe FISH and standard HER2 IHC
were performed on formalin fixed paraffin embedded tissue blocks
PS-23-010
at a UK laboratory and scored as per UK guidelines.
Renal stone disease in an XVIII century mummy from Popoli, central
Results: Immunohistochemistry was done on 91 samples. The HER2 +3
Italy
tumours accounted for 10% (n=9), the +2 (equivocal) tumours were 11%
L. Ventura1, A. Fornaciari2, A. Calabrese3, L. Arrizza4, G. Fornaciari2
1 (n=10) and the negative 0/+1 tumours were 79% (n=72). FISH was done
Division of Pathology, San Salvatore Hospital, L'Aquila, Italy,
2 on 20 samples (19 +3 and +2 tumours by immunohistochemistry and 1
Division of Paleopathology, Department of Translational Research
negative sample), however the test failed in 5 cases. By FISH,74% (n=11)
and New Technologies in Medicine and Surgery, University of Pisa,
of the tumours were amplified, with 83% (n=5) of the IHC +3 cases and
Italy, 3 Division of Radiology, Santissima Trinità Hospital, Popoli, Italy,
4 75% (n=6) of the +2 IHC tumours showing gene amplification.
Centre of Microscopies, University of L'Aquila, Italy
Conclusion: This study shows that by FISH, a significant percent-
age of equivocal cases on IHC had gene amplification and these
Background & Objectives: A natural, well-preserved mummy be-
cases should benefit from anti-HER2 therapy. Further work into
longing to an anonymous 35-40 years old male was found in a
improving the pre-analytical factors such as fixation is needed to
crypt beneath the Church of the Holy Trinity in Popoli, central
minimise the test failure rate.
Italy. Fine clothes and burial location suggested high social sta-
tus and an important role in the church community. Probably, he
was a nobleman, member of the congregation of the Holy
PS-24-002
Trinity. Artifacts helped in dating back the individual to the
Pathology services in a low resource setting: University of Abuja
early 1800’s.
Teaching Hospital, Abuja, Nigeria experience
Methods: The body was secured to a cardboard layer by a plastic film
O. Oluwole1
and recovered from the crypt to be submitted to visual inspection, X-ray 1
University of Abuja, Nigeria
Virchows Arch

Background & Objectives: The practice of pathology in the devel- ±11.87. They had an average satisfaction level of 46.31%, 31.57%,
oping world, where the majority of the earth’s population lives, 18.24%, 52.63%, 46.31% and 38.24% in turnaround time, diagnos-
presents special challenges for the Western-trained physician ac- tic accuracy, notification of critical alerts, laboratory test ordering
customed to the high standard of living, long life expectancy, and system, appropriate result reporting system and courtesy of staff
predictable disease patterns that are prevalent in the developed respectively. Responsiveness of laboratory staff turned out to be
world. 69.47%. Physicians were most dissatisfied (18.24%) with reporting
ObjectiveTo highlight how pathology services in a low resource of critical alerts in cytology.
setting is been used to meet the health needs of our populace, Conclusion: As the satisfaction of physicians towards cytopatholo-
teach medical students and getting involved in international col- gy services was average in most of the parameters, therefore, ap-
laborative studies. propriate measures should be taken and implemented effectively to
Methods: The use of specimen accessioning, gross specimen ex- improve the service quality and standards of specialized cytopa-
amination and automatic tissue processing to produce quality mi- thology services with professional ethics. Efforts should be made
croscopic slides using routine, haematoxylin and eosin (H&E) at both individual and organizational level to provide best possible
stain. Fine needle aspiration cytology services, a low-cost and services to our valuable customers.
reliable diagnostic technique is available in our laboratory. This
also contribute significantly to the number of specimens processed
in the laboratory. As we speak there is no immunohistochemistry PS-24-004
services in our facility, but we can access it in sister hospitals Potential and utility of YouTube for teaching and learning in surgical
close to us. pathology; resident's perspective from Pakistan
Results: In a year, we received and processed around 4000 surgi- S. Mahmood1, F. Rehman1, F. Iqbal1, S. Ahmad1, M.Z. Sarwar1, A.
cal specimens and around 2500 fine needle aspiration cytology Momina1
1
specimens including Papanicolau smears. We diagnosed around King Edward Medical University, Lahore, Pakistan
200-300 cancer cases that comprises of cervical, breast, prostate,
ovarian, gastrointestinal tract, endocrine, lymphoid and some from Background & Objectives: A biggest dilemma in training of the
the central nervous system. surgical pathology residents of third world countries is lack of
We have been involved in the following international research skilled and trained supervisors, insufficient technical support, pro-
collaborative studies; African Collaborative Microbiome and vision of ancillary studies and low quality reagents and limited
Genetic Research: PI, Clement Adebamowo; AIDS-Malignancies exposure to all specialties. Aim of this study was to determine
study: PI, Clement Adebamowo; Sub-Saharan Africa Lymphoma effectiveness and utility of various video logging & channels
study: PI, Leona Ayers. available on YouTube in the education and training of surgical
Conclusion: Pathology services in low resource setting may be pathology residents working in public sector laboratories of
rudimentary, but it is undergoing gradual transformation in spite Lahore.
of the challenges that has bedeviled it and there is room for much Methods: A cross sectional survey analysis was done and the data
development. Pathologists from the developed world can play a collected from 77 surgical pathology residents working at both
critical role in providing support for locally adapted services in public & private sector laboratories. A questionnaire was de-
low-resource nations, acting in cooperation with local medical signed covering different aspects of usefulness and practicality
and government Institutions. of social networking sites in surgical pathology. Students were
asked to fill the questionnaire after the written informed consent
is taken. The questionnaire consists of 25 survey questions on the
PS-24-003 potential use of Youtube for teaching and education of surgical
Physicians satisfaction with cytopathology services; an experience at pathology residents. A 5-point Likert scale was used as follows:
a tertiary care hospital in Lahore 1- Strongly agree; 2- agree; 3 – unsure; 4 – disagree; 5 – strongly
S. Mahmood1, S. Sarwar1, S. Shahid2, F. Rehman1, S. Ahmad1, M.Z. disagree.
Sarwar1 Results: The findings show that YouTube can be used as an in-
1
King Edward Medical University, Lahore, Pakistan, 2 CMH Medical structional tool in surgical pathology in line with current trends of
College, Lahore, Pakistan collaboration and social networking in pathology education. The
analysis shows that the instructional videos for teaching and learn-
Background & Objectives: Physicians are an integral part of the ing especially through live streaming of slide sessions, case series,
cytopathology services in determining the quality of laboratory gross cutup of surgical specimens and various advanced techniques
work. Their feedback is a useful quality indicator in determining can be effectively channelled through YouTube. The YouTube is
the standard of laboratory procedures and parameters towards the also beneficial for providing information, as well as for teaching
improvement in the service delivery. Aim of this study is to and learning in the surgical pathology.
evaluate the satisfaction level of requesting medical practitioners Conclusion: With an increasing tendency to use social networking
regarding cytopathology services so that the issues can be ad- sites in the recent decade, YouTube has played a pivotal role in
dressed appropriately. the training of surgical pathology residents. Video blogging is an
Methods: A cross sectional study was conducted through a self- effective strategy to teach residents using a combination of
designed questionnaire by distributing it to 375 physicians of supporting text, images, live streaming and other metadata.
mayo hospital, Lahore which is a tertiary care hospital affiliated Core knowledge is currently less represented in you tube content.
with King Edward Medical University, Lahore. Ethical approval The findings of this study indicate the integration of information
for this study was taken from ethical review board of the technology in learning and teaching the surgical pathology can be
Institution. Data was analysed by using SPSS 22. done using YouTube. In the context of teaching and learning,
Results: The overall respondents were 285 (76%) in which 78.6% YouTube is used as a video repository to assist both lecturers
were male and only 21.3% were females with a mean age of 38.18 and students.
 Virchows Arch

Methods: Cases of AFX, PDS, UPS and AFH were searched in

Wednesday, 11 September 2019, 09:30 - 10:30, Agora 3
our diagnostic archive database. We retrieved clinical and patho-
PS-25 | Soft Tissue and Bone Pathology
logical characteristics from the original reports and reviewed all
cases and slides in order to confirm diagnosis and to assess mor-
PS-25-001 phological and immunohistochemical (IHC) features. Main focus
Identification of SRF-STAT6 fusion transcript in a cellular was on p53 (TP53), p63 (TP63) and CD10 IHC.
myofibroma of the forearm in a 15 years-old boy: expanding the Results: We reviewed 141 cases (64 AFX/PDS, 6 UPS, 70 AFH,
molecular spectrum of the recently described entity 1 sarcoma ex AFH). 21.9 % of AFX/PDS patients were female
C. Bouvier1, H. Nihous2, F. Le Loarer3,4, J. Massière5, N. Macagno1, F. (AFH: 47.1 %); mean age was 80 years (AFH: 42 years). AFX/
Tirode6, J.L. Jouve7, J.C. Gentet8, D. Figarella Branger9 PDS and AFH expressed CD10 in 98.3 % and 100 %, whereas
1
Service d'anatomie pathologique et de neuropathologie Hopital de la p63 was negative in 92.3 % (AFX/PDS) and 100 % (AFH). Of
Timone, France, 2 Service d'anatomie pathologique et de neuropathologie 21 AFX/PDS tested for TP53 IHC, all showed aberrant expression
hopital de la Timone, France, 3 Department of Biopathology, Institute (13/21 positive, 8/21 null-type). In contrast, 11/13 AFH stained
Bergonie, Bordeaux, France, 4 University of Bordeaux, Talence, for TP53 had wildtype expression.
France, 5 INSERM U1812, Institute Bergoniè, Bordeaux, France, Conclusion: While CD10 does not separate AFX/PDS and head
6
INSERM 1052 centre Lèon Bèrard, France, 7 Service de chirurgie and neck AFH, aberrant TP53 immunostain seems to be specific
orthopèdique Hopital d'enfants de la Timone, France, 8 Service for AFX/PDS versus AFH.
d'oncologie pèdiatrique Hopital d'enfants de la Timone, France,
9
Service d'Anatomie pathologique et neuropathologie Hopital de la
Timone, France PS-25-003
A challenging diagnosis in paediatric pathology: BCOR-CCNB3
Background & Objectives: The spectrum of mesenchymal tumours sarcoma
keeps increasing with the input of NGS. Recently myofibroblastic I. Gullo1,2,3, K. Mazzocco4, F. Buffelli4, A. Zin5, A.R. Sementa4
1
tumours arising within deep soft tissue with high cellularity and a Department of Pathology, Centro Hospitalar de São João, Porto,
more differentiated immunophenotype towards myoid lineage have Portugal, 2 Department of Pathology, Faculty of Medicine of the
been described harboring a recurrent SRF-RELA fusion. University of Porto (FMUP), Portugal, 3 Institute of Molecular
Methods: We report the case of a 15 years old patient who presented with Pathology and Immunology at the University of Porto (Ipatimup),
a calcified soft tissue mass of the forearm. Instituteo de Investigação e Inovação em Saúde (i3S), Portugal,
4
Results: Histological examination showed a moderately cellular IRCCS Istituto Giannina Gaslini, Italy, 5 Institute of Paediatric
fascicular proliferation mainly composed of spindle cells with Research (IRP), Fondazione Città della Speranza, Italy
variable eosinophilic cytoplasm. However areas of higher cellular-
ity with more basophilic cells were also seen giving a biphasic Background & Objectives: Breast metastases are rare. They repre-
appearance. Tumour stroma contained calcifications. There was no sent 0.4 to 6% of all breast cancers. Our aim is to discuss their
necrosis and mitotic index was 1 mitosis/50HPF. Cells stained for clinicopathological features.
alpha smooth actin, H-caldesmon and desmin but were negative Methods: We report a retrospective survey of 12 cases of breast
for myogenin, MyoD1, CD34. CGH-array showed no copy num- metastases diagnosed over a period of 23 years (1992—2016) in
ber alteration. As a cellular myofibroma/myopericytoma with the department of pathology of the university hospital of Sfax
SRF-RELA fusion was suspected, whole RNA-sequencing was (TUNISIA).
performed leading to identify SRF-STAT6 fusion that joined SRF Results: The diagnosis was carried on a material of cytoponction
exon 5 to STAT6 exon 17. Tumour cells diffusely stained for in two cases, a needle biopsy in seven cases and a surgery spec-
STAT6 by immunohistochemistry. Tumour profile clustered with imen in three cases. The primary tumours understood two cases
classical SRF-RELA tumours. of small cell non-Hodgkin lymphoma, a case of nasopharyngeal
Conclusion: Our case of myogenic soft tissue tumour with SRF- carcinoma, a case of retroauricular melanoma, a case of
STAT6 fusion expands the morphological and molecular spectrum leiomyosarcoma, a case of uterine choriocarcinoma, a case of
of the SRF-rearranged lesions. rectal neuroendocrine carcinoma, a case of small cell lung
carcinoma, three cases of gastric adenocarcinoma and one case
of a hematological malignancy of underminated origin. All pa-
PS-25-002 tients were women with a middle age of 37 years. In only one
Immunohistochemical TP53 expression in atypical fibroxanthoma case the mammary metastasis revealed the primary tumour.
and their mimics Clinically, the size average of tumours was 2.9 cm. Bilateral
R. Erber1, A. Hartmann1, A. Agaimy1 mammary involvement was noted in three cases.
1
Institute of Pathology, University Clinics Erlangen, Friedrich-Alexander Conclusion: A confrontation of clinical and pathological data with
University Erlangen-Nürnberg, Germany immunohistochemical study is recommended for an accurate diag-
Background & Objectives: Atypical fibroxanthoma (AFX) is a nosis of breast metastasis.
cutaneous neoplasm composed of spindle and pleomorphic cells,
mainly arising in the sun-damaged skin of head and neck sites.
Differential diagnosis comprises pleomorphic dermal sarcoma PS-25-004
(PDS), undifferentiated pleomorphic sarcoma (UPS), spindle cell Inflammatory myofibroblastic tumour: a case series and immunohis-
und desmoplastic squamous cell carcinoma (SCC), smooth mus- tochemical work-up and prognostic follow up study
cle neoplasms, nerve sheath tumours, angiosarcoma, spindle cell Ü. Kutlu1, P.G. Ergun1, Ů Batur1, N. Kepil1, N. Çomunoğlu1
1
und desmoplastic melanoma and atypical fibrous histiocytoma Istanbul University Cerrahpasa-Cerrahpasa Medical Faculty
(AFH). Department of Pathology, Turkey
Virchows Arch

Background & Objectives: Inflammatory myofibroblastic tumour ±16.7years-old (Range: 12-86 years). Most common localizationS
(IMT) is a mesenchymal neoplasm that may arise in soft tissues were knee (53.8%, n=21) followed by hip (15.4%), ankle (12.8%)
of nearly every organ and it is usually seen in paediatric popula- and elbow (10.3%), rare localisations were wrist, shoulder, and
tion. IMT is characterised by the presence of myofibroblasts and metatarsophalangeal joint (2.6% for each). No correlation was
inflammatory cells within a fibrous stroma. Screening of the lit- found between histological features and localization of lesions,
erature revealed the fact that all studies based their research on age and gender of cases.
one anatomic location. In this study we share our IMT experience Conclusion: Most of our cases were located around knee joint,
by presenting 32 cases, comparing their immunohistochemical consistent with the literature. However we observed rare localiza-
(IHK) staining pattern, and follow up data. tions as ankle, hand and foot joints. Synovial lining over the
Methods: The patients archives of Pathology Department of nodules was not a constant feature and the nodules showed in-
Istanbul University –Cerrahpaşa Cerrahpaşa Medical Faculty was creased cellularity, nuclear pleomorphism and hyperchromatism
inspected retrospectively. Immunohistochemical stains that were which can be mistaken for a low grade chondrosarcoma if the
applied to all cases are: SMA, ALK and p53. The cases which exact localization of cases are not known.
lack one or more of those stains in their original IHK panel were
completed afterwards, the blocks which were used in the original
immunohistochemical work-up were used. PS-25-006
Results: Total of 32 IMT cases were detected. Female to male ratio was Distinct histologic and genetic characteristics of round cell sarcoma
1.4:1 (19/13). The mean value of age is 32 (2-86). The mean of tumour with CIC-DUX4 or BCOR-CCNB3 fusion and comparison with
diameter is 7.5 cm (0,5-23 cm). Lungs were the most frequent location Ewing sarcoma
(7/32), followed by bladder (6/32). Rare locations of ovary, orbita and M.J. Song1, J.S. Song2, K. Cho2
1
femoral bone were detected, 1 case for each. 25/32 of the cases were Department of Pathology, Kyung Hee University Hospital at
stained positively for SMA, 18/32 for ALK, 15/32 for p53. 6/32 cases Gangdong, Republic of Korea, 2 Department of Pathology, Asan
reoccurred during follow up. Medical Center, Republic of Korea
Conclusion: Our case series is the only large series of IMT’s oc-
curring in different locations, and it investigates differences in Background & Objectives: CIC-DUX4 and BCOR-CCNB3 fusion
histopatholgic appearance, immunohistocemical staining properties gene associated sarcoma is a new emerging subgroup of round
and clinic behaviour in correspondence with tumour location. Rare c e l l s a r c o m a w i t h E w i n g s a r c o m a - l i k e m o r p h o l o g y.
localisations for IMT were seen in our series, such as long bone, Distinguishing these tumours from Ewing sarcoma family tumour
ovary and heart. 6 out of 32 cases presented with recurrence. Only (ESFT) is still challenging. The present study 1) investigated CIC-
one case was treated with chemotherapy, other cases were treated DUX4 or BCOR-CCNB3 fusion in small round cell sarcoma, 2)
with surgery only. examined clinicpathologic and immunohistochemical characteris-
tics of CIC-DUX4 or BCOR-CCNB3 sarcoma, and 3) evaluated
diagnostic parameters.
PS-25-005 Methods: Seventy patients diagnosed with undifferentiated round
Synovial chondromatosis - a retrospective review cell sarcoma or Ewing–like sarcoma in Asan Medical Center were
M. Sezak1, O. Oz2, E. Buyuktalanci3, E. Kaya Bicer4, B. Doganavsargil5 investigated. The inclusion criteria were as follow: 1) EWSR1
1
Ege University Faculty of Medicine Department of Pathology, Turkey, translocation was negative or non-informative by molecular test
2
Bergama Hospital, Department of Pathology, Turkey, 3 Ege University and 2) available tumour tissue for molecular analysis. EWSR1
Faculty of Medicine Department of Pathology, Turkey, 4 Ege University FISH was performed to exclude ESFT. CIC-DUX4 and BCOR-
Faculty of Medicine Department of Orthopaedics, Turkey, 5 Ege CCNB3 gene fusion was investigated by RT-PCR. The clinical
University Faculty of Medicine, Department of Pathology, Izmir, Turkey and histologic phenotypes were reviewed. CD99, NKX2.2,
Caveolin-1, BCOR and NUT immunohistochemical stains were
Background & Objectives: Synovial chondromatosis is a benign performed and assessed the diagnostic value to differentiate
nodular cartilaginous proliferation arising in the synovium of Ewing sarcoma.
joints, bursae or tendon sheaths. Grossly round or oval shaped Results: We identified six cases of CIC-DUX4 sarcoma but
loose bodies-like nodules ranging 0.1-3 cm are seen. It is fre- BCOR-CCNB3 sarcoma was not detected. Compared to ESFT,
quently encountered in adults and in larger joints as knee and they demonstrated short event-free survival (P=0.034) and poor
shoulder. Histologically it is characterised with sy\novial lined response to treatment (P=0.007). Histologically, heterogeneous
cartilaginous nodules with varying degree of cellularity, especially round, plasmacytoid, and spindle cells were observed. Unlike
at the periphery of nodules, therefore can be mistaken for a Ewing sarcoma, severe cytologic pleomorphism, multinucleated
chondroid malignancy in biopsy specimens. cells and myxoid stroma were common. CD99 and NKX2.2 com-
Methods: We retrospectively reviewed the cases diagnosed in a sin- bination test may be helpful to differentiate CIC-DUX4 / BCOR-
gle center between 1986-2016 years. Cellularity (1=enchondroma- CCNB3 sarcoma from Ewing sarcoma.
like, 2=Slightly appearent, 3=appearent), nuclear pleomorphism (fo- Conclusion: CIC-DUX4 sarcomas have distinct histologic features
cal/diffuse), presence of calsification- Ossification were evaluated and poor prognosis compared with ESFT. Therefore, molecular
and correlated with clinicopathological features. analysis to detect the distinctive genetic alteration is mandatory
Results: Thirty-nine cases were identified with an equal gender in small round cell tumours with atypical histologic, immunohis-
distribution (male/female ratio:0.95) Median agewas 54 tochemical and/or clinical presentation.
 Virchows Arch

Poster Sessions One-Day CPS and Two-Day Methods: The validation model consisted of diagnosing sets of slides
from different topographic areas with one training-step and one valida-
MDS tion-step. The pathologist first read the cases digitally and directly after-
wards using a microscope. Diagnostic discrepancies were recorded, as
well as cases deferred to traditional microscopy. The training step
consisted of approximately 20 slides. The validation step used a mini-
Sunday, 8 September 2019, 09:30 - 10:30, Agora 3
mum of 60 cases. For pathologists validating more than one set, a mini-
PS-CP-01 | 1-Day Computational Pathology Symposium mum of 30 cases was used in subsequent sets.
Results: We collected 18 sets (10 pathologists, 8 areas) corresponding to
PS-CP-01-001 1058 cases in the validation step. A total of 10 cases was excluded.
Can image recognition techniques on whole slide images of colorectal Included were 1048 cases (approx. 10711 slides), while 24 cases (2.3%) were
polyps help in the identification of areas of high grade dysplasia? deferred to traditional microscopy. In 5 cases, a diagnostic discrepancy was
P. De Paepe1, J. Van Huysse2, A. Driessen3, P. Niville4, W. Van Laer4, recorded. The diagnostic concordance (deferred cases excluded) was 99.5%.
K. De Wolf4 Frequently commented discrepancies (not diagnosis-altering) regarded
1
AZ Sint-Jan, Brugge-Oostende, Dept of Pathology, Belgium, 2 AZ St scanning- and tissue quality, cell details, mitoses, small objects and
Jan Brugge-Oostende, Dept of Pathology, Belgium, 3 University Hospital dysplasia.
Antwerp, Dept of Pathology, Belgium, 4 Ixor, cvba Schuttersvest 75 2800 Conclusion: The diagnostic concordance of 99.5% between digital diag-
Mechelen, Belgium nostics and microscope indicates that digital microscopy is a safe alterna-
tive to traditional microscopy.
Background & Objectives: Colorectal screening programs have re-
sulted in a significant increase in the number of colorectal polyps in
Monday, 9 September 2019/Tuesday, 10 September 2019,
daily pathology practice. The aim of the study is to design a model,
09:30 - 10:30, Agora 3
based on deep learning techniques, that recognizes and indicates
major zones of interest on whole slide digital images (WSI) of PS-MD-01 | 2-Day Molecular Diagnostics Symposium
colorectal polyps. The zones of interest are: normal mucosa, zones
with low grade dysplasia and zones with high grade dysplasia as PS-MD-01-001
defined by the WHO criteria. Expression of Transient Receptor Potential Vanilloid-1 in gliomas vs
Methods: With a digital drawing tool three pathologists identified the medulloblastomas
zones of interest on 73 WSI. Only zones indicated by all three were used M. Assimakopoulou1, A. Moutafidi1, V. Zolota2, G. Gatzounis3
to design and train a first deep learning model focusing on pattern recog- 1
Department of Anatomy-Histology and Embryology, School of
nition. Each WSI was subdivided into tiles, 256x256 pixels. Medicine, University of Patras, Greece, 2 University of Patras, School
Next 9804 tiles, clearcut examples of the zones of interest, were selected of Medicine, Greece, 3 Department of Neurosurgery, University
to retrain the model. These tiles were subdivided into a training set Hospital of Patras, Greece
(8656), a validation set (786) and a test set (362).
Results: The final model reached a 75% accuracy on recognizing high Background & Objectives: The non-selective cation channels
grade dysplasia with a recall of 90% on the test set, 93% accuracy and Transient Receptor Potential Vanilloid (TRPV) of TRP superfamily
84% recall on low grade dysplasia and 77% accuracy and 81% recall on are activated by numerous stimuli and thus, may mediate down-
normal tissue. stream signalling. Previous data implicates alterations of TRPV1
Conclusion; Our study demonstrates the possibility to develop a machine expression in growth and progression of gliomas. Additionally,
learning model that indicates zones of major interest in WSI’s. Improving low or absent TRPV1v3 variant expression has been strongly corre-
our model among other by increasing the number of WSI for training, will lated with short survival in glioblastoma multiforme (WHO, grade
allow us to develop a pre-diagnostic tool that offers support to the pathol- IV) patients. The aim of this study was to investigate the expression
ogist and may help to provide an accurate pathology report at appropriate levels of TRPV1 channel in gliomas and compare with embryonal
time. tumours such as medulloblastomas.
Methods: Immunohistochemistry was performed in formalin-fixed,
paraffin-embedded tissue sections from 81 human brain tumours
PS-CP-01-002 and samples from normal brain, using specific primary antibody
Low discordance rate of digital diagnostics of histopathology com- against TRPV1. Analysis of immunoexpression was defined as the
pared to conventional microscopy - results from 1048 cases in a val- percentage of positive (labelled) cells out of the total number of
idation study tumour cells counted in ten non-overlapping fields (Labelling in-
S. Jarkman1, A. Bodèn1,2, B. Williams3,4, J. van der Laak5, D. Treanor4 dex, LI). The results were confirmed by immunofluorescence and
1
Department of Pathology, Linkoping University Hospital, Sweden, 2 qRT-PCR.
Department of Clinical and Experimental Medicine, Linkoping Results: TRPV1 cytoplasmic localization was detected in tumour
University, Sweden, 3 Histopathology Department, St James University cells of gliomas and in neurons and a few glial cells of normal brain
Hospital, Leeds, United Kingdom, 4 University of Leeds, United specimens. All medulloblastomas were TRPV1-immunonegative. In
Kingdom, 5 Radboud University Medical Center, The Netherlands contrast, TRPV1-immunopositive gliomas (LI≥10) included 62.50%
of diffuse fibrillary astrocytomas (WHO, grade II), 71.42% of ana-
Background & Objectives: Since 2011 the Department of Anatomical plastic astrocytomas (WHO, grade III), 53.33% of glioblastomas
Pathology in Linköping, Sweden, is routinely digitizing all histopatho- multiforme (WHO, grade IV), 14.28% of oligodendrogliomas, and
logical glass slides. Implementation of a novel diagnostic modality re- 33.33% of ependymomas. No significant association between
quires careful validation. Our validation model is designed in cooperation TRPV1 channel expression and patients’ clinicopathological charac-
with Leeds University Hospital, UK, and is adapted to the local circum- teristics was found.
stances. This validation study, ongoing since 2016, aims to investigate if Conclusion: Given the cellular heterogeneity, and the distinct cells of
diagnoses made digitally are concordant with traditional microscopic origin of different brain tumours, further functional studies would clarify
diagnoses. the role of TRPV1 in biological behaviour of these tumours.
Virchows Arch

PS-MD-01-002 set of liquid biopsy samples collected from a human subject with NSCLC
Validation of a novel approach for molecular breast cancer during the course of 15 months. The results showed that a well-known
classification TP53 mutation R248Q was consistently detected in the longitudinal sam-
S. Baldacchino1, J. Debattista2, C. Saliba3, C. Scerri4, G. Grech1 ples. Interestingly, additional gene amplifications including MET, CDK4
1
Department of Pathology, University of Malta, Malta, 2 Applied Biotech and FGFR3 were identified at late time points, which were also confirmed
Ltd, Malta, 3 Centre for Molecular Medicine and Biobanking, University by digital PCR and showed concordant with FISH analyses in solid tumour.
of Malta, 4 Department of Physiology and Biochemistry, University of Conclusion: Overall, this study demonstrates that Pan-Cancer assay pro-
Malta vides a unique and complete NGS solution for comprehensive genetic
mutation assessment using in vitro and in vivo liquid biopsy models.
Background & Objectives: The current breast cancer diagnostic
workflow is subject to pre-analytic variables, interpretation and defined
thresholds. Despite updated guidelines, equivocal and inter-laboratory PS-MD-01-004
disconcordance persist in current methodologies for HER2 assessment. Case report: NGS of cell-free DNA from blood and bile as a follow-up
The validation process for a novel molecular breast cancer classification strategy in a patient with metastatic pancreatic adenocarcinoma
method is outlined. K. Ebner1, C. Driescher2, W. Goering3, L. Haeberle2, V. Keitel1,
Methods: 660 breast cancer specimens were cored (0.5mm) and arranged D. Haeussinger1, I. Esposito2
1
into a TMA. Cases selected were equally distributed as HER2 positive, Department of Gastroenterology, Hepatology and Infectious Diseases,
negative or equivocal by immunohistochemistry. The TMA was assessed Heinrich Heine University and University Hospital, Germany, 2 Institute
for HER2, ER and PR immunohistochemistry and HER2 FISH. TMA of Pathology, Heinrich Heine University and University Hospital,
cores were then retrieved, lysed and analysed using a bead-based Germany, 3 Institute of Pathology, Heinrich Heine University and
Quantigene assay. Data was controlled for quality and processed using University Hospital, Germany
a developed algorithm to classify molecular breast cancer subtypes.
Results: In a pilot study (N=108) the Quantigene assay showed a 100% Background & Objectives: A 65-year-old patient initially presenting to our
sensitivity and 93.5% specificity for HER2 detection. Considering the non- clinic with jaundice and weight loss was diagnosed with metastasized pan-
equivocal HER2 cases, Quantigene showed a 100% sensitivity and 100% creatic ductal adenocarcinoma. After undergoing ERCP for biliary stent im-
specificity concordant with HER2 immunohistochemistry. Equivocal cases plantation, chemotherapy with Gemcitabin/nabPaclitaxel was initiated. After
(2+) (n=35) tested by Quantigene show 100% Specificity and 80% initial therapy response, we aimed at monitoring disease development by
Sensitivity compared to the HER2 FISH confirmatory result. using a liquid biopsy approach with NGS analysis of cell-free DNA
Conclusion: A new molecular pathology tool has been developed for the (cfDNA) extracted from serially collected blood and bile samples.
classification of breast cancer using a diagnostic-ready approach with Methods: Blood samples were collected at study inclusion and during
control material, minimal turnaround time and low cost. outpatient-visits after 4, 7 and 14 weeks. Bile was collected at study
inclusion and 7 weeks later during routine ERCP for biliary stent replace-
Supported by Project “Accurate Cancer Screening Tests” (ACT) financed ments. After cfDNA extraction and quantification, panel-based NGS
by the Malta Council for Science & Technology through FUSION: The analysis was performed using Ion-S5 next generation sequencing plat-
R&I Technology Development Programme 2016. form. Additionally, results were compared to mutation profiles obtained
from tissue samples of the primary tumour.
Results: During tumour progression, primary tumour mutations in TP53
PS-MD-01-003 and KRAS were detected in blood with rising allele frequencies (AF) from
Characterisation of genetic mutation spectra and identification of 13.9% and 13.2% after 4 weeks to 25% and 19.7% after 7 weeks. Bile-
gene amplification and fusion variants in cell-free nucleic acid from derived cfDNA after 7 weeks showed TP53 and KRAS mutations with AF
cultured cancer cell media and liquid biopsy specimens using of 5.5% and 4.4% compared to 0.3% and 0.2% at study inclusion. After
Oncomine™ pan-cancer cell-free assay modification of the chemotherapy-regimen, ultrasound-based detection
R. Cao1, K. Lea1, J. Schageman1, K. Hanif1, Y. Li1, J. Gu1, V. Bagai1, of regression of liver metastases was accompanied by decreasing AF of
P. Kshatriya1, A. Luchetti2, L. Quagliata1, H. Wikman3, S. Loges3, TP53 and KRAS mutations in blood-cfDNA to 1.1% and 1.0%.
K. Bramlett1 Conclusion: This report suggests that mutation profiles of cfDNA from
1
ThermoFisher Scientific, USA, 2 Thermo Fisher Scientific, Italy, blood as well as bile might be useful in monitoring tumour development
3
Department of Tumour Biology, Center of Experimental Medicine, and therapy response. Larger cohort studies remain necessary to investi-
University Medical Center Hamburg-Eppendorf, Germany gate the potential of this method for therapy-surveillance and possible
benefits over routine biomarkers.
Background & Objectives: Currently the standard practice in tumour bio-
marker research still relies on invasive tumour biopsy following by molecular
testing or NGS assay. However, this only provides limited characterization of PS-MD-01-005
tumour composition. Recent studies in non-invasive biomarker research have Effect of radio-wave and molecular resonance surgery on rat neck
demonstrated the potential advantages of using cell-free nucleic acids isolated skin regeneration
from blood plasma to study genetic heterogeneity of tumour population and I. Kastyro1, P. Pryanikov2, A. Alsufev1,3, V. Popadyuk1, A. Kovalenko1,
dissect the complex cancer clonal architecture. A. Sedelnikova1, N. Kamanina1
1
Methods: Recently developed Oncomine™ Pan-Cancer Cell-free Assay Peoples' Friendship University of Russia (RUDN University), Russia,
2
employs an amplification-based approach from Ion Torrent NGS technol- Pirogov Russian National Research Medical University (RNRMU),
ogy and achieves exceptional sensitivity and specificity with input as little Russia, 3 Greenberg City Clinical Hospital Perm, Russia
as 20 ng. It includes comprehensive genetic content to simultaneously
interrogate both cfDNA and cfRNA. Background & Objectives: Presently, modern methods of electrosur-
Results: In this study, cancer cell lines harboring multiple variant types gery are necessary for conducting surgeries, especially in emergency
were selected for evaluation. Using Pan-Cancer Cell-free Assay, we suc- conditions, such as when tracheostomy is performed in patients with
cessfully detected all the expected variants in these cancer cell lines includ- tumour laryngeal stenosis. The aim of the work was to compare the
ing gene amplification (MET, ERBB2, CDK4) and fusion variants (ALK effects of radio-wave (RW) and molecular resonance (MR) surgery on
fusion and MET exon skipping). Subsequently, we applied this assay to a rat neck skin regeneration.
 Virchows Arch

1
Methods: Cuts were made with a microsurgical RW generator (1group) Genetic Counseling Unit, University Hospital for Tumours, Sestre
and a MR generator (2group) on neck skin of 10 rat's. Cytological study Milosrdnice University Hospital Center, Zagreb, Croatia, 2 Lab. for
of preparations obtained using the superficial biopsy method (May- Hereditary Cancer, Div. of Molecular Medicine, Institute Rudjer
Grünwald stain). Cytograms were determined for 5 types according to Boskovic, Zagreb, Croatia, 3 Lab. for Advanced Genomics, Div. of
M.F.Kamaev. After surgery at 1,2,4,6,8,10&12 days rats were scored 2 Molecular Medicine, Institute Rudjer Boskovic, Zagreb, Croatia
from each group and a histological study of postoperative wounds (H&E,
toluidine blue stain). In assessing morphological changes we evaluated Background & Objectives: Our Hospital introduced Genetic counseling
necrosis,the severity of inflammatory changes, edema, proliferative and testing for patients affected with breast/ovarian cancer or healthy
changes, epithelization. individuals from hereditary breast and ovarian cancer families. BRCA1/
Results: Cytological examination showed that from day 2 the number of 2 gene testing was indicated in individuals who met the criteria according
neutrophils decreased in gr.1 (p<0.01), and from day 5 the number of to the Clinical Practice Guidelines.
fibroblasts increased, compared with gr.2 (p<0.005). In gr.1, the thickness Methods: BRCA1/2 germline mutations were analysed in whole blood
of the necrosis is less than in gr.2 (87.5+8.1 against 112±6.5), from day 3, samples using next-generation sequencing, Sanger sequencing and quan-
edema (p<0.005), the mast cells number (p<0.005) and neutrophilic in- titative PCR methods. We compare pathohistological characteristics of
filtration of the wound edges were more in group 2 (p<0.005), prolifera- breast cancer in BRCA-mutation carriers and non-carriers.
tive changes and epithelialization were better in gr.1 (p<0.001). Results: BRCA1/2 was tested in 153 women, and 20 of them carry
Conclusion: RW exposure is a more effective way of transforming electric germline BRCA1/2 mutation: 16 in the BRCA1 gene, 4 in BRCA2 gene
energy in the vibration of tissue molecules, which allows to achieve the and 3 had a BRCA2 variant of unknown significance. We collected data
dissection at lower power output, as compared to the MR method. This on 57 breast cancer patients, of which 12 were BRCA mutation carriers.
studies have revealed that the inflammatory response and the healing time BRCA-positive women with BC were younger at the time of diagnosis
for wounds are significantly less after RWexposure compared to MR method. than women without BRCA mutations (median 38.5 years vs. 45.5 years).
Among BRCA-positive patients, 75% had triple-negative breast cancer
The publication has been prepared with the support of «RUDN (TNBC), 16.7% had Luminal/HER2 positive BC and 8.3% with Luminal/
University Program 5-100». HER2 negative BC. Among BRCA-negative patients, only 9.5% had
TNBC, 66.7% had Luminal/HER2 negative BC, 16.7% had Luminal/
HER2 positive and 7.1% had HER2 enriched BC. Patients with
PS-MD-01-006 BRCA2 variant of unknown significance had Luminal/HER2 negative
Up-converting nanoparticles as a tool for histopathological tissue breast cancer. Although the average size of the tumour was larger in
evaluation with multiplexing and machine learning potential BRCA positive patients (25 mm vs. 18 mm), there is no difference in
K. Krawczyk1, S. Andersson-Engels2, A. Sjögren1 median size of the tumour (15mm).
1
Lumito AB, Sweden, 2 Biophotonics@Tyndall, Tyndall National Conclusion: Detection of family members with germline BRCA1/2 mu-
Institute, Cork, Ireland tations may play a vital role in breast cancer risk assessment and
surveillance/treatment plan.
Background & Objectives: In the field of histopathology, a risk for misdiag-
nosis is a serious issue. A standard way to visualise cell morphology is through
H&E staining often combined with DAB chromogenic stain. However, this PS-MD-01-008
method suffers from narrow dynamic range, problems with quantitation and Comparison of four microsatellite instability testing methods in en-
difficulties with multiplexing and co-localisation. Fluorescent IHC techniques dometrial cancer- reliability, handling, cost effectiveness
generate a more quantitative readout but suffer from photobleaching. Here we J. Siemanowski1,2, B. Schömig-Markiefka1,2, W. Dietmaier3,4, N. Arens5,
present that the use of up-converting nanoparticles (UCNPs) allows to over- T. Buhl1,2, R. Büttner6, S. Merkelbach-Bruse7
1
come problems associated with commonly used imaging techniques. University Hospital Cologne, Germany, 2 Institute of Pathology,
Methods: Novel luminescent UCNPs were used together with a prototype Germany, 3 University Regensburg, Germany, 4 Institute of Pathology,
instrument to image selected markers, e.g. Her2, in the human tissue. Germany, 5 Molecular Pathology Trier, Germany, 6 Institute for
Formalin-fixed paraffin-embedded human colon and breast cancer tissues Pathology, Cologne, Germany, 7 Institute of Pathology University
were sectioned and stained using autostainer. UCNP fluorescence imaging Hospital of Cologne, Germany
of the human tissue sections was compared with a standard DAB based IHC.
Pulsed excitation and gated detection were explored to improve the scanning Background & Objectives: Microsatellite instability (MSI) is a common
speed. UCNP and H&E co-staining and co-imaging were also investigated. alteration in endometrial cancers caused by aberrations in the DNA mismatch
Results: Images obtained with our novel device clearly show that devel- repair system and recently designated as a predictive biomarker for response
oped by us antibody-UCNP conjugates can be used to successfully stain to immune checkpoint therapy. Differences in MSI profiles between endome-
the human tissues. Brightfield images show that UCNPs are not visible in trial and colorectal cancers enable the possibility of false negative results in
white light and hence do not interfere with standard tissue evaluation by a routine diagnostic. This study compares four different PCR based testing
pathologist. Additionally, brightfield and luminescent images can be approaches initially designed for the detection of MSI in colorectal cancer.
merged to provide better understanding of tissue morphology. Methods: 25 endometrial tumours with immunohistochemically di-
Conclusion: Emerging field of UCNPs opens up new possibilities. agnosed stable, instable and uncertain microsatellite status were se-
Staining solutions and a novel device developed by us give hope for more lected. Tumour and paired normal tissue DNA was extracted from
accurate diagnosis by keeping the advantage of H&E staining and com- formalin-fixed, paraffin-embedded (FFPE) material. MSI testing
bining it, in one image, with luminescent data, ideal for generating ground was performed by fragment length analysis with an in-house
truth for machine learning algorithms. Bethesda-Panel and the MSI Analysis system (Promega) as well as
parallel sequencing with a custom GeneRead V2 panel (Qiagen).
10 μm slices of the same FFPE tumour tissues were taken for the
PS-MD-01-007 Idylla MSI assay (Biocartis).
Pathohistological characteristics of breast cancer in BRCA-positive Results: All four methods showed a high overall concordance and could
and BRCA-negative women clarify uncertain MSI status due to inaccurate IHC. Analysis and inter-
S. Ramic1, I. Kirac1, T. Oresic1, T. Zigman1, V. Musani2, P. Ozretic2, pretation of results was more time consuming with the Bethesda-,
O. Vugrek3, I. Milas1 Promega-Panel and the parallel sequencing Approach.
Virchows Arch

Conclusion: This study showed that all MSI testing methods provided name (1.00), date of birth (1.00), the assay used (0.125), targeted aberra-
reliable results for MSI testing albeit dealing with difficulties during in- tions (0.25) and the reference sequence (0.25). For other items only indi-
terpretation of results. The Idylla MSI assay seems to be a suitable alter- vidual feedback was given.
native to the other assays due to easy result interpretation and cost effec- Results: The average reporting score was 3.12/4 (N=17) based on the
tiveness caused by short hands on time without the need of normal tissue. presence of 7 elements. Interpretations received average scores of 67%,
50% and 44% for cases 1, 2 and 3, respectively. In case 3, a resistance
mutation was detected but not the activating mutation because not
PS-MD-01-009 targeted by the test method. The latter was recommended to be clearly
Association between KRAS, NRAS, BRAF mutation status and clin- stated in the interpretation. Elements like the sampling date (59%), reason
icopathological prognostic factors in colorectal carcinoma in Turkish for testing (59%), DNA extraction method (47%), method sensitivity
population (53%) and reference sequence (18%) were only present on a limited
D. Unal Kocabey1, E. Cakir1, F.H. Dilek1, B. Bolat Kucukzeybek1, number of reports.
A. Calli2 Conclusion: This ring trial showed that there is still room for improve-
1
Izmir Katip Celebi University Ataturk Training and Research Hospital ment regarding reporting molecular pathology results. As liquid biopsy
Department of Pathology, Turkey, 3 Dokuz Eylul University Molecular testing has only recently entered daily practice, a clear and correct report
Medicine, Turkey might further educate prescribing oncologists. Further initiatives on im-
provement are currently being set-up.
Background & Objectives: KRAS, NRAS and BRAF mutations have
prognostic and predictive value in colorectal carcinoma (CRC). The K. van Casteren and K. Dufraing are first authors in equal proportions.
aim of this study is to investigate frequency of KRAS, NRAS, BRAF The research project was funded by a grant from N.V. AstraZeneca S.A.
mutations in Turkish CRC patients and to evaluate their relationship with
clinicopathological prognostic factors.
Methods: All CRC patients who underwent surgical resection from 2008 PS-MD-01-011
to 2018 and tested for KRAS, NRAS, BRAF mutation at our Institution Establishment of a 3D histopathology platform for precision tumour
were analysed retrospectively. The association between KRAS, NRAS, diagnosis
BRAF mutation status and clinicopathological prognostic factors includ- J. Yang1, Y. Lin2,3, A. Chiang2,4, I. Wang5, S. Wu6, M.D. Chang7, J. Lee8,
ing age, sex, tumour site, tumour size, histological grade, pT stage, pN J. Ko9, S. Liang9, J. Guo10, X. Song10, H. Huang10, M. Chao11, C. Lin12
1
stage, lymphovascular invasion, perineural invasion, tumour deposit were Department of Life Science, National Tsing Hua University, Hsinchu,
compared statistically. Taiwan, 2 Brain Research Center, NTHU, Taiwan, 3 JelloX Biotech,
Results: A total of 137 patients with CRC were retrieved. KRAS, Hsinchu, Taiwan, 4 Institute of Systems Neuroscience, NTHU, Taiwan,
5
NRAS and BRAF mutations were detected in 34.6% (47/136), Institute of Biotechnology, NTHU, Taiwan, 6 Department of
13.2% (12/91) and 3.6% (2/56) of tumours, respectively. We identi- Engineering and System Science, NTHU, Taiwan, 7 Institute of
fied KRAS mutations in codon 12, 13, 59 and 146 in 70.2% (33/47), Molecular and Cellular Biology, NTHU, Taiwan, 8 Oncology
21.3% (10/47), 6.4% (3/47) and 2.1% (1/47), respectively. Also, we Department, National Taiwan University Hospital Hsin-Chu Branch,
found NRAS mutations in codon 12, 61, 13, 59 in 41.7% (5/12), 25% Taiwan, 9 Internal Medicine Department, National Taiwan University
(3/12), 16.7% (2/12), 16.7% (2/12), respectively. While absence of Hospital Hsin-Chu Branch, Taiwan, 10 Pathology Department, National
KRAS mutation was significantly associated with perineural invasion Taiwan University Hospital Hsin-Chu Branch, Taiwan, 11 Surgery
(P = 0.002), there was no significant association between KRAS mu- Department, National Taiwan University Hospital Hsin-Chu Branch,
tation status and other clinicopathological features. Similarly, there Taiwan, 12 Oncology Department, National Taiwan University Hospital,
was no significant association between NRAS and BRAF mutation Taipei, Taiwan
status and clinicopathological features.
Conclusion: The effect of KRAS, NRAS and BRAF mutations on clinico- Background & Objectives: Rapid and accurate evaluation of full picture
pathological features is unclear. Future studies with larger patient groups of histopathological biopsy has clinic unmet need. We thus aim to estab-
can help to clarify the association between KRAS, NRAS, BRAF mutations lish an automated 3D histopathology platform that emerges comprehen-
and clinicopathological features. sive pathologic images in support of quantitative data analyses and
standardised digital format to overcome technology limitation of current
2D image diagnosis tools.
PS-MD-01-010 Methods: The platform offers an innovative optical tissue clearing im-
Results of the Belgian ring trial for liquid biopsy testing in non-small mersion system with high-resolution of 3D image technology, employing
cell lung cancer show variety in the interpretation of the test result alternative scanning and slicing processes reliable depth control of con-
K. Van Casteren1, K. Dufraing1, P. Pauwels2, N. D'Haene3, E. Dequeker1 tinuous automatic images and digital suture parallel multi-stack images,
1
Biomedical Quality Assurance Research Unit, KU Leuven, Leuven, and thus panoramic 3D digital images of a complete histopathological
Belgium, 2 Laboratory of Pathological Anatomy, Antwerp University sample are produced.
Hospital, Edegem, Belgium, 3 Department of Pathology, Erasme Results: The platform allows detection in-depth and comparative analy-
University Hospital, Brussels, Belgium sis of normal and pathological organization. Moreover, our innovative
database stores high resolution images of deep tissues that are suitable
Background & Objectives: The use of liquid biopsies for detect- for building up artificial intelligence algorithms. The 3D-AI assisted path-
ing resistance mutations after disease progression in patients with ological modules in detecting malignant cancer cells in mouse lung can-
non-small cell lung cancer has been introduced into routine. This cer model and in clinical metastatic breast to lymph nodes model will be
study aimed to evaluate how well laboratories interpret and report demonstrated in ECP 2019.
test results. Conclusion: Our automated 3D histopathology platform could provide
Methods: Laboratories participating in the Belgian EGFR ctDNA Ring intact deep tissue histopathological database for practical application of
Trial 2018 (N=17) received 3 mock requests and test results from fictional AI auxiliary precision medicine.
patients for which they had to submit reports resembling their daily rou-
tine. Reports were assessed based on pre-defined scoring criteria. Marks Supported by MOST106-3114-8-007-001, Ministry of Science and
were given for the test result (0.75), clinical interpretation (0.625), patient Technology, Taiwan.
 Virchows Arch

E-Posters the last case, an adrenal nodule with alveolar growth pattern of slightly
enlarged cells was diagnosed as a cortical adenoma.
Conclusion: Although rare in necropsy, adrenal masses should be inves-
tigated as they may reveal potential severe diseases and tanathogenesis
Sunday, 8 September 2019 – Wednesday, 11 September 2019 significance. Immunohistochemistry may be useful to discriminate spe-
E-PS-01 | Autopsy Pathology cific types of tumours, in correlation with the clinical information, gross
findings, and microscopic features in routine staining.

E-PS-01-001
Pulmonary fibrosis as a manifestation of connective tissue disease E-PS-01-003
E. Malysheva1, S. Timofeev1, E. Startseva1, N. Zharkov1 Secondary meningo-cerebral tumours with unknown lung primaries
1
City Hospital of Moscow, Russia - necroptic features
C. Amalinei1, A. Grigoras2, C. Teodorescu3, L. Riscanu1,3, L. Lozneanu1
1
Background & Objectives: Pulmonary fibrosis is a complex issue, so "Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania,
2
much so that determining the true causes of this disease has been a stum- Department of Morphofunctional Sciences I-Histology, "Grigore T.
bling block for pulmonologists and pathologists for many years. More Popa" University of Medicine and Pharmacy, Iasi, Romania, 3 Institute
recently, however, our understanding of pulmonary fibrosis has devel- of Legal Medicine Iasi, Romania
oped to such an extent that researchers have discovered that there are
similarities between patients with pulmonary fibrosis and those with a Background & Objectives: Most common central nervous system
connective tissue disease. tumours represent metastases and the primary tumour has usually
Methods: A 48-year-old woman was admitted to hospital and diag- been already diagnosed. Metastases of unknown primaries may be
nosed with pneumonia. Her medical history informed us of child- discovered in forensic pathology. The aim of our study is to report the
hood asthenia and hypermobility of the joints. Despite treatment, particular features in eight cases of meningo-cerebral metastases di-
her condition worsened and she died. The cause of death was pul- agnosed during the last three years, in our Department, in subjects
monary heart disease. The autopsy revealed deformation of the with age range between 55 and 80 years old, five men and three
chest, sometimes seen in patients who suffer from a connective women.
tissue disease. Lungs had pleural and perivascular fibrosis. The lu- Methods: Routine hematoxylin-eosin and Masson’s trichrome staining,
men of the alveoli had a mixture of desquamated epithelium with along with immunohistochemistry using a panel of markers (CK7, TTF1,
macrophages and hyaline membranes. CK5, p63, AE1/AE3, CK20, and HepPar1) have been performed.
Results: Epithelium cells of the alveolar lining and stroma cells had a Results: Gross appearance was that of sharply delimited lesions,
positive reaction with plasminogen activator inhibitor type 1 (PAI-1), “dot mainly disposed at the gray-white matter junction, of 1-2 cm diam-
like” cytoplasmic staining. eter, containing variable necrosis and haemorrhage. Microscopy re-
Stroma cells, perivascular spaces and walls of blood vessels were mark- vealed multiple lesions with variable location: cerebrum, brainstem,
edly positive with antibodies to type IV collagen and positive with cerebellum, meninges, along with meningeal carcinomatosis (in
CD117 / c-kit. three cases). Liver metastases have been also found in two cases
The lumen of the alveoli and the interstitial spaces had a significant and have been excluded in a case with an ectopic adrenal gland. The
amount of HLA-DR and CD68-positive cells, which formed clusters in primary tumours have been identified as seven cases of lung adeno-
the cavity of the alveoli. carcinomas and one squamous cell carcinoma.
Conclusion: Despite the patient suffering from symptoms related to con- Conclusion: Metastases of lung carcinomas have to be considered
nective tissue disease, including weight loss, chest deformation and hy- in meningo-cerebral malignancies. Differentials should include pri-
permobility of the joints, the main manifestation of the disease was actu- mary meningo-cerebral tumours and the final diagnosis has to be
ally pulmonary fibrosis. certified by corroboration of comparative size between primaries
and secondaries, characteristic multiple, secondary lesions, includ-
ing the possibility of additional liver metastases, along with spe-
E-PS-01-002 cific expression of immunohistochemical markers and microscopic
Incidental adrenal tumours in forensics features.
C. Amalinei1, L. Lozneanu1, B. Ioan1,2, L. Riscanu1,2, A. Grigoras3
1
"Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania,
2
Institute of Legal Medicine Iasi, Romania, 3 Department of E-PS-01-004
Morphofunctional Sciences I-Histology, "Grigore T. Popa" University Post-mortem diagnosis of metastatic male breast cancer with fulmi-
of Medicine and Pharmacy, Iasi, Romania nant evolution
D. I. Enea1, M. Ceausu2, A. Tita2, G. Roman2, M. Bosa2, L. Luca2, O.
Background & Objectives: Adrenal masses are rare, incidental findings Neagu1, L. Tomescu1
1
in forensic pathology. The aim of our study is to report the particular University Emergency Hospital, Bucharest, Romania, 2 "Mina
features of four cases, occurred in 50-69 years old subjects, two females Minovici" National Institute of Legal Medicine, Bucharest, Romania
and two males.
Methods: Routine hematoxylin-eosin, along with immunohistochemistry Background & Objectives: Male breast cancer is a rare form of malig-
using synatophysin, chromogranin, S100, MelanA, and inhibin, in two nancy which develops from the small amount of residual breast tissue
selected cases, have been performed. found in men. It usually affects older men with a background of hormonal
Results: Gross findings were variable. Microscopy revealed, in two imbalances, but the risk factors are not entirely known.
cases, circumscribed areas of alveolar growth pattern and cytologic vac- Methods: This report describes an unusual case of breast cancer in a 60-
uolar degeneration, synaptophysin+, chromogranin+, S100+ (focal), year-old man with obesity and vertebral algic symptoms. MRI exam
MelanA-, and inhibin-, characteristics of pheocromocytoma. One of them highlighted multiple lytic lesions of the spine, including T12-L2 patho-
had vascular invasion, and multiple tumoural implants, being diagnosed logical fractures. Subsequent clinical examination revealed a left breast
as metastatic malignant pheocromocytoma. In another case, islands of mass. Due to rapid deterioration of the patient’s condition, followed by
metastatic implants of a lung adenocarcinoma have been detected. In exitus (<1 month), any further investigations couldn’t be performed and
Virchows Arch

the diagnosis remained uncertain. The autopsy detected cirrhosis, a left was a food leakage from the tracheostomy, so it was put a nasoenteral
breast tumour and metastasis in the spine. tube. He evolved with dyspnea, bulky tracheostomy bleeding and death.
Results: Microscopically, there was an invasive carcinomatous prolifer- Results: Macroscopy: a surgical specimen measuring 10x8x7cm
ation composed of pleomorphic cells arranged in nests, trabeculae, cords, where we identified proximal portion of the trachea, larynx, thy-
with desmoplastic stroma, located in the breast, lungs and liver. By means roid and related structures, compromised by tumour lesion of ill
of immunohistochemistry, the tumour cells showed positive reaction for defined, grayish and friable limits. Microscopy, an undifferentiated
AE1-AE3, ER (~ 1-5 %) and a high proliferation rate (PCNA ~ 80-90%). malignant neoplasm with pleomorphic giant cells, parts of them
The histopathological findings suggested a poorly differentiated, highly fusiform, with sarcomatous aspect, presenting vesiculous nucleus
aggressive, invasive ductal carcinoma of no special type (NST) of the with macronucleolus, many bizarre mitosis figures, extensive areas
breast with liver, lung and bone metastasis. of necrosis and hemorrhagic focus. Tumour cells are arranged in
Conclusion: The particularity of this unusual case resides in rapid evo- solid blocks and infiltrate widely the thyroid parenchyma, skeletal
lution of an aggressive, metastatic, male breast cancer, with a high rate of muscle adjacent, larynx and trachea, which causes complete lumi-
proliferation, on a background of a delayed diagnosis due to a misleading nal obstruction. Also compromises angiolymphatic structures and
tumour appearance, in the context of hormonal imbalance caused by perineural spaces adjacent.
cirrhosis and obesity. Conclusion: The case shows a rare episode of anaplastic thyroid cancer
in which the symptoms appeared after a trauma. Therefore, it is necessary
a fast identification and establishment of a effective therapeutic, looking
E-PS-01-005 after a better care for the patient.
Multi-organic infiltration by anaplastic large celllymphoma, ALK
positive, diagnosed in autopsy
A. M. G. Pereira1, F. Galante Pereira1, C. A. Padrão1, A. T. Alves2 E-PS-01-007
1
Hospital Prof. Doutor Fernando Fonseca, EPE, Portugal, 2 Instituto de Giant intraventricular thrombi as a complication of chronic abuse of
Anatomia Patológica da Faculdade Medicina Universidade de Lisboa, cocaine-levamisole
Portugal K. Metze1, N. Biagioni de Lima1, R. Lanaro1, C.A. de Lima1
1
State University of Campinas, Brazil
Background & Objectives: ALK-positive (ALK+) anaplastic large cell
lymphoma (ALCL) is a T-cell lymphoma that accounts for approximately Background & Objectives: Giant intraventricular thrombi in the heart
3% of adult non-Hodgkin lymphomas and frequently involves both are a rare phenomenon. They can be caused by different conditions such
lymph nodes and extranodal sites, most commonly the skin, bone, soft as antiphospholipid syndrome, heparin-induced thrombocytopenia, ma-
tissue, lungs, and liver. lignant neoplasias, Takotsubo cardiomyopathy, hypereosinophilic syn-
Methods: Diagnosing lymphoma is not easy, and the clinical presentation drome or aluminium phosphide poisoning. An important pathophysiolog-
of this 64 years old man we are presenting was challenging and mislead- ical mechanism for many different conditions seems to be an endothelial
ing with high fever, heterogeneous hepatomegaly and diarrhea. Clinical dysfunction. The aim of this case report was to show that chronic cocaine-
presentation suggested an infectious disease and a possible consumptive levamisole abuse can also cause giant ventricular thrombi.
process supported by a story of weight loss. Empiric antibiotic therapy Methods: A 44-year old man with a history of chronic cocaine abuse was
was started and the CT-scan report found multiple adenomegalies and admitted to hospital with necrosis of the toes. Angiography revealed multiple
hepatomegaly with areas of nodular hipocaptation suggestive of small arterial and venous thrombi in both legs and pulmonary thromboemebolism.
abscesses. Blood tests also revealed acute renal and liver failure. Echocardiography suggested biventricular giant thrombi of the heart.
Results: With rapidly progressive health deterioration, the man died after Although submitted to anticoagulation treatment with heparin and symptom-
three days and, without a definitive diagnosis, an autopsy was requested. atic therapy, the patient evolved to hemodynamic instability and expired on
An extensive infiltration by ALK+ ALCL was documented, involving all the sixth day. An autopsy was performed.
the lymph nodes that were observed plus the liver, lung, bone marrow, Results: Autopsy revealed widespread veonous thrombosis in both legs,
spleen, kidneys, adrenal glands and the myocardium. recurrent pulmonary thrombembolism with infarcts and giant thrombi in
Conclusion: We present this case to highlight how even an extensive and both cardiac ventricles as well as gangrene of the distal parts of all fingers
advanced stage ALCL can “fly under the radar” and involve some less and toes due to thrombotic arteritis. Toxicologic hair analysis showed
common and rare extranodal sites. chronic abuse of cocaine mixed with levamisole for at least 6 months.
Conclusion: Levamisole, an antihelminth and immunomodulatory adju-
vant, is an adulterant in cocaine worldwide. Widespread venous throm-
E-PS-01-006 bosis and thrombotic arteritis suggest generalized endothelial dysfunction
Anaplastic Carcinoma Thyroid in a cervical trauma: an autopsy as the leading pathophysiological mechanism which might also eplain the
report genesis of the giant thrombi.
J. Melo1, E. Ribeiro de Lemos2, M.C. Carneiro da Ibiapaba2, T. In summary, we describe cocoaine–levamisole intoxication as a new pre-
Guimaraes do Nascimento2, L. Camelo Oliveira2, L. Macedo Pinto2, D. disposing condition for intracardiac giant thrombi most probably related
Nunes Oliveira1, D. Nunes de Melo3 to a generalized endothelial dysfunction.
1
Department of Pathology, Postgraduate Program in Public Health, Faculty
of Medicine, University of Fortaleza, Brazil, 2 Faculty of Medicine, Supported by CNPq
University of Fortaleza, Brazil, 3 State Secretary of Health, Brazil

Background & Objectives: Anaplastic thyroid carcinoma (ATC) is one Sunday, 8 September 2019 – Wednesday, 11 September 2019
of the most aggressive cancers Report a case of Anaplastic thyroid cancer E-PS-02 | Breast Pathology
which symptoms were triggered after a car accident.
Methods: Autopsy was made in Legal Medical Institute. Male, 51 years
E-PS-02-001
old, victim from a car accident three months ago suffered a anterior
Squamous cell carcinoma of the breast with apocrine features: a rare
cervical trauma steering wheel injury. A few days later, he evolved with
variant of metaplastic breast cancer
a bulky anterior cervical mass, hoarseness, an obstructive respiratory
C. Taverna1, A.G. Naccarato2, C. Scatena3
insufficiency and was submitted to an urgent tracheostomy. After, there
 Virchows Arch

1 1
Division of Pathological Anatomy, Department of Health Sciences Regional Institute of Oncology, Iasi. Romania, 2 Department of
University of Florence School of Human Health Sciences Florence, Pathology, Regional Institute of Oncology, Iasi, Romania
Italy, 2 University of Pisa, Italy, 3 Division of Pathology, Department of
Translational Research and of New Technologies in Medicine and Background & Objectives: Primary neuroendocrine carcinomas of the
Surgery, University of Pisa, Pisa, Italy breast represent a rare entity, with incidence under 0.1% from all breast
carcinomas and under 1% from all neuroendrocrine carcinomas. We pres-
Background & Objectives: Small-cell neuroendocrine carcinoma of lung is ent the case of an 56-year-old woman with a single solid nodule in the
one of the most frequent types within endobronchial biopsies. Although it right breast, admitted to the surgical oncology department of Regional
shows characteristic histopathological finding, immunohistochemistry is nec- Institute of Oncology Iasi, Romania. Five days prior to the admission the
essary in many cases due to the variety of possible differential diagnoses. The lesion was discovered during a routine screening mammogram. The pa-
expression of the different markers usually employed as CKAE-1AE3, TTF- tient has no significant past medical history.
1 and neuroendocrine markers varies according to the literature. In particular, Methods: The routine screening mammogram revealed a well
it is very important to know that these neoplasms can show negative immu- circumscribed homogeneous nodule of 12/10 mm situated in the lower
nostain for epithelial markers and even for TTF-1. inner quadrant of the right breast, considered low-risk. No additional
Methods: The archive were reviewed between the years 2009-2014, abnormalities were found. It was performed a core-biopsy, and two frag-
obtaining 110 cases. There were 97 mens and 13 women.The median ments of tissue of 7 and 4 mm were fixed with formalin 10%, paraffin
age was 72 ( range betwen 41 to 90 year old). We studied 78 biopsies embedded and analysed using hematoxylin and eosin staining and
and we also included 32 cases of lung FNA. immunohystochimical tests.
Results: From 110 cases we found 7.27% that were negative for TTF1 Results: Microscopy revealed uniform small cells separated by delicate
immunostain, 1.8% with negative immunostain for CKAE1-AE3. The rest fibrovascular stroma. Tumour cells have round nuclei with granular chro-
of performed neuroendocrine markers were chromogranin, synaptophysin matin, scant cytoplasm, mitosis and apoptosis. Cells were positive for
and CD56, which were negative in 11.92%, 22% and 2.75% respectively. synaptophysin, chromogranin and TTF-1, negative for estrogen and pro-
Conclusion: There are few bibliographical references to the percentage gesterone receptors. HER2neu was 0 (negative). After immunohisto-
of negativity for TTF1 and CKAE1-AE3 in this tumour. The negativity chemical analysis the differential diagnosis was made with a metastasis
for CKAE1-AE3 and TTF-1 is considered extremely rare. This study from another primary neuroendocrine tumour. PET/CT and abdominal
contributes important information, since it characterises immunoprofile ultrasound excluded a non-mammary primary site. The patient received
of small-cell carcinoma. This information is useful in cases that show a chemotherapy and radiotherapy.
usual morphology of small cell neuroendocrine carcinoma but with un- Conclusion: Primary neuroendocrine carcinoma of the breasts is a rare
usual immunohistochemical expression. tumour, classified as a type of invasive mammary carcinoma with distinc-
tive histopathological features. It exhibits morphological features similar
to those of neuroendocrine tumours of the gastrointestinal tract and the
E-PS-02-002 lung, therefore it is crucial to make an accurate diagnosis and first exclude
Sebaceous carcinoma of the breast in a male patient with a BRCA2 a metastasis in the breast.
germline mutation: case report and literature review
J. Lobo1, P. Lopes1, R. Henrique1, î Rodrigues1
1
IPO Porto, Portugal E-PS-02-005
Low grade breast adenosquamous carcinoma: a clinicopathological
Background & Objectives: Sebaceous carcinoma (SC) is an overall uncom- and genetic study
mon neoplasm. Its occurrence on the breast is very rare. We aim to present a R. Ondruššek1
1
case of primary SC of the male breast in the context of a BRCA2 mutation. CGB laboratory a.s., Czech Republic
Methods: A 79-year-old man complained of a breast lump detected on
self-examination. Core-biopsy reported “grade 2 invasive carcinoma with Background & Objectives: Low grade adenosquamous carcinoma
secretory pattern”. He was referred to our Institution and underwent left (ASC) of the breast is an unusual and rare variant of metaplastic triple-
total mastectomy was performed. Macroscopically, a hard, well- negative carcinoma with excellent prognosis. Tumour is characterised by
circumscribed and lobulated, yellowish, 1.9cm nodule was depicted. It small well-developed glandular formations intimately admixed with solid
was centered in breast parenchyma and the overlying skin/nipple-areolar nests of squamous cells in a spindle-cell background. Triple negative
complex were unremarkable. carcinomas are included in heterogenous group of tumours with thera-
Results: Histologically, it corresponded to an invasive carcinoma, with peutic limitations. Specific changes in several genes can help to offer
nested architecture and no evidence of cutaneous origin. >80% of the targeted therapy.
tumour displayed large clear cells, with microvacuolated cytoplasm, Methods: In 2018 we diagnosed mammary ASC in three female patients in
admixed with smaller basophilic cells. Intraductal carcinoma with same the segmentectomy specimens. We evaluated clinical data, pathological fea-
features was present. It was diffusely positive for ER/PR/AR/EMA, and tures and genetic profiling retrospectively. TP53, EGFR, PTEN, CDKN2A
negative for HER2/GCDFP15. A diagnosis of SC of the breast was made. genes were investigated by fluorescence in situ hybridization (FISH).
The patient’s daughter had been diagnosed with breast cancer at age 44 Results: The median age of patients was 74 years (ranging from 70 to
and the patient was found to carry a BRCA2 mutation. 79), tumour diameters 0.2 – 2.7cm, TNM stage pT1a - pT2. Sentinel
Conclusion: Compliance with strict criteria proposed in WHO 2012 is nec- lymphatic nodes were available for their evaluation in 2 out of 3 patients
essary for clearly discriminating this entity from breast cancer with sebaceous and no metastases were found. FISH did not demonstrate amplification
differentiation and from SC of the overlying sebaceous glands. This is the first EGFR gene (7p11), deletion PTEN gene (10q23), deletion TP53 gene
case of SC of the breast in a male patient with a germline BRCA2 mutation. (17p13) deletion CDKN2A gene (9p21). All cases showed typical histo-
PhD Grant by FCT (grant number SFRH/BD/132751/2017). pathological features of low grade ASC with conspicuous stromal lym-
phocytic aggregates.
Conclusion: This study confirms excellent prognosis of ASC of the
E-PS-02-004 breast without sentinel lymphatic nodes involvement and where available
Case report: a 56-year-old woman with primary neuroendocrine genetic testing turns out to be negative. We suggest that lymphocytic
carcinoma of the breast aggregates might be useful and significant morphological feature to im-
M. Dieaconu1, D. Ferariu2 prove diagnosis in breast low grade ASC.
Virchows Arch

E-PS-02-006 Results: Molecular subgroups of the BC cases were distributed as fol-

Breast adenomyoepithelioma: potential pitfalls in the diagnosis lows: luminal A -45.91%; luminal B HER2- positive - 25.46%; luminal B
S. Aviel-Ronen1, J. Simon2, M. Papa3, G. Gitstein4 HER2- negative -18.64%; triple negative-18.18%; HER2- positive -
1
Department of Pathology, Sheba Medical Center, Tel-Hashomer, Israel, 10%.The majority of cancer samples had histological grade (G) 2, to a
2
Institute of Diagnostic Radiology, Meuhedet Health Maintenance lesser extent G1 and G3 were recognized. Luminal B group, both positive
Organization, Rehovot, Israel, 3 Surgery Department, Assuta Medical and negative, a statistically significant positive correlation was
Center, Tel Aviv, Israel, 4 Pathology Department, Sourasky Medical established between the indicators (Spearman correlation coefficient:
Center, Tel Aviv, Israel 0.410521 and 0.403631, respectively). Luminal B group, both positive
and negative, had a high correlation between G and Ki67 expression
Background & Objectives: Adenomyoepithelioma of breast is a rare be- (Spearman correlation coefficient: 0.410521 and 0.403631, respectively).
nign tumour of the epithelial-myoepithelial group of lesions. This tumour is Other molecular subgroups of the BC had a low correlation between
characterised by proliferation of myoepithelial cells surrounding small mentioned variables.
epithelium-lined spaces. Here we describe a case of adenomyoepithelioma Conclusion: In order to assess the biological aggressiveness of a
and discuss the potential pitfalls in the diagnosis. breast cancer, a further IHC study of apoptosis and intercellular
Methods: The medical records, imaging tests and pathological findings adhesion needed.
of a 64 patient have been studied and are presented. A suspicious left
breast semi-cystic lesion, 1 cm in diameter, was identified on screening
mammography. The core needle biopsy that was performed showed un- E-PS-02-008
usual and non-conclusive histological characteristics, therefore a com- Maligant phyllodes tumour cum CDIS: case report
plete excision of the lesion was advised. Subsequently, lumpectomy W. Michej1, W. Olszewski2, J. Owczarek2
1
was performed. Cancer Centre Instytute Warsaw, Poland, 2 Cancer Centre Instytute,
Results: On lumpectomy, a cellular multi-lobulated lesion was identified. Poland
The lesion showed proliferation of bland spindle cells occasionally sur-
rounding gland-like structures. Neither nuclear atypia nor mitotic activity Background & Objectives: Malignant phyllodes tumour is a rare case
were identified. Many myoepithelial cell markers including p63, end develops in older women. The recognition demands macroscopic,
calponin, caldesmon, podoplanin and CD10 were negative. However, microscopic end immunuhistochemical description. The characteristic
CK 5/6, S100 and SMA stained diffusely the tumour cells, while ER stain whorled pattern, curved clefts is seen in the most lesions. Histologically
highlighted the epithelium-lined spaces. In spite of the partly contradic- - a combination of marked nuclear plemorphism of stromal cells, mitotic
ting immunostain results, it was concluded that the lesion is a benign activity, permeative margins. The aim of this case report is to highlight
adenomyoepithelioma. characteristic details to make a good recogniction of phyllodes tumour
Conclusion: Myoepithelial cells show diverse appearance with their var- and differentiate from metaplastic carcinoma. It is important for futher
ious immunostain markers and demonstrate differences in their staining treatment after surgical removing.
sensitivity in different lesions. Therefore, it is crucial to use a broad panel Methods: A 50 years old woman was operated due to 3,0cm tumour of
approach and address the morphological features in order to reach an breast. Grossly well defined, grey tumour was revealed. H-E examination
accurate interpretation of epithelial-myoepithelial lesions. showed many pleomorphic cells, necrosis and unregular mitotic figures.
Between such pictures the structures of CDIS NG1 were also present. The
question was: is it a malignant phyllodes tumour with CDIS or metaplas-
E-PS-02-007 tic carcinoma? Many of immunohistochemical reactions were done. The
Prognostic value of proliferation marker assessments in patients with final diagnosis was - malignant phyllodes tumour (pleomorphic sarcoma)
different biological subtypes of breast cancer with CDIS low grade.
L. Rudiuk1,2, O. Reshetnikova3, S. Korenev1 Results: The woman was observed in our institute. After two years she
1
Immanuel Kant Baltic Federal University, Kaliningrad, Russia, developed a small lump in the same breast. Histologically it had only a
2
Regional Clinical Hospital of the Kaliningrad region, Kaliningrad, pattern of pleomorphic sarcoma identical to the primary tumour. The
Russia, 3 Immanuel Kant Baltic Federal University, Russia component of CDIS was absent. It confirmed our diagnosis that it was
a malignant phyllodes tumour.
Background & Objectives: Breast cancer (BC) is the most common Conclusion: This case shows the possibility of coexistence of malignant
cancer and the second leading cause of cancer-related death among wom- transformations two components in phyllodes tumour. It is important to
en. BC remains an important health issue worldwide. make a good diagnosis because of futher treatment. The recogniction of
The aim of this study was to correlate tissue expression of proliferation metaplastic carcinoma implicates more aggresive treatment after surgery
biomarker Ki-67 with different immunohistochemical (IHC) subtypes of i.e. chemotherapy. After diagnosis of malignant phyllodes tumour with
breast cancer and to assess the relationship of Ki-67 to tumours histolog- CDIS low grade, excision within healthy limits until recurrence is recom-
ical grading. mended.
Methods: This was a retrospective study including 220 female patients with
breast cancer. The histological diagnosis was performed on formalin-fixed
and paraffin-embedded breast tissue blocks from pretreatment biopsies and E-PS-02-010
mastectomies. Tumour grading was determined according to Elston&Ellis. Interobserver agreement between pathologists assessing tumour-
IHC analyses were carried out with the help of following monoclonal mouse infiltrating lymphocytes in breast cancer by applying international
antibodies: to ER (RTU, Bond 6F11), PgR (RTU, Bond 16), HER2 TILs Working Group recommendations
(Novocastra, CB11 1: 250). Ki67 expression was tested with monoclonal R. Ayadi1, D. Bacha2, O. Belkacem2, R. Yaiche2, A. Ben Amor3, S.
mouse antibodies (RTU, MM1) and then proliferation activity was deter- Gharbi2, A. Lahmar2, S. Bouraoui2
1
mined as a percentage of the stained parenchymal component of an invasive Pathology Department, Military Hospital, Tunis, Tunisia. University of
breast carcinoma of a no special type (in 10 microscopic fields of view per Tunis El Manar, Faculty of Medicine of Tunis, Tunisia, 2 Pathology
1000 cells at magnification x400). Relation between the tumour grade and department, Mongi Slim Hospital, University Tunis El Manar,
proliferative activity in biological subgroups of the BC were assessed by Medicine Faculty of Tunis, Tunisia, 3 Department of Gynaecology-
Spearman's rank correlation coefficient. High correlation between the two Obstetrics, Mongi Slim Hospital, University Tunis El Manar, Medicine
variables got rank 1 (r=1). Faculty of Tunis, Tunisia
 Virchows Arch

Background & Objectives: Several studies highlighted the prognostic Background & Objectives: Malignant mesenchymal tumours of the
and predictive values of tumour-infiltrating lymphocytes (TILs) in breast breast, other than angiosarcomas, are rare and comprise <0,5% of breast
cancer (BC). tumours. Primary leiomyosarcoma of the breast is an extremely rare tu-
The aim of this study was to determine interobserver agreement between mour with <40 cases reported till date. We present a case of primary
pathologists using the International TILs Working Group recommenda- leiomyosarcoma of the breast.
tions for the assessment of stromal TILs (sTILs) in BC. Methods: A 55-year-old female presented to our hospital complaining
Methods: We retrospectively analysed 53 hematoxylin and eosin stained for pain with a large lump in her left breast for the last 6 months.
slides of invasive BC, obtained from 26 core needle biopsies and 27 Mammography and ultrasonography revealed a well-circumscribed tu-
surgical resections. Three pathologists independently reviewed each slide mour measuring 9x7cm in size, located in the upper quadrant of the left
and evaluated sTILs. We used Fleiss’s kappa statistics to calculate the breast. FNA revealed evidence of malignancy and the patient underwent
overall proportion of interobserver agreement. total mastectomy of the left breast and axillary lymph node dissection.
Results: The average age was56.5 years.The kappa statistic for sTILs Results: Microcopically, the tumour was composed of pleomorphic spin-
assessment was 0, 55 with15 discrepancies cases.Discordances were dle cells arranged in intersecting fascicles and bundles, showing frequent
mostly noted in surgical resection specimens (37%) compared to micro- mitoses and necrosis. On immunohistochemistry the tumour cells were
biopsies (19%) and interested mainlyTILs proportions in intervals (5- positive for SMA and desmin and negative for S100p and CD117. Based
10%) and (40-50%).Discrepancies reasons included the difficult distinc- on the immunomorphological features, the tumour was diagnosed as
tion between carcinomatous cells and lymphocytes or granulocytes.In all leiomyosarcoma.
samples, there has been a tendency to increasingTILs average rates in the Conclusion: Leiomyosarcoma of the breast may originate from the
presence of a focal hot spot zone.Artefactual retraction spaces helped to smooth muscle of the lactiferous ducts of the nipple and the surrounding
distinguish carcinomatous clusters from stromal inflammatory infiltrate. blood vessels. Differential diagnosis includes leiomyoma, spindle cell
Conclusion: Acceptable agreement in sTILs assessment was noted when myoepithelioma and spindle cell sarcomatoid carcinoma. The prognosis
applying the international TILs Working Group recommendations. Sample is better than that of other breast sarcomas. The prognostic factors are not
fixation quality, which is better in micro-biopsies specimen, and a suitable fully known because of the limited number of studies. The benefits of
contrasting staining, play an important role in the distinction between cell types. chemotherapy, radiotherapy and hormonal therapy are still controversial.
However, there is a need for further studies to determine the prognostic
factors.
E-PS-02-011
Comparative evaluation of immunological micro-environment in the
study of trepanobiopsy specimens and operational material of inva- E-PS-02-013
sive breast carcinoma Peptidil argenin deiminase typ 4 level in blood samples of women
A. Semenova1, O. Isaeva1, A. Vagenin1, M. Bogatyreva1 with different molecular-genetic subtypes of breast cancer
1
Chelyabinsk Oncology Clinic, Russia A. Semenova1, O. Tereshin1, A. Vagenin1, I. Dolgushin2
1
Chelyabinsk Oncology Clinic, Russia, 2 South-Ural Medical University,
Background & Objectives: To assess differences in the representation of Russia
lymphocyte subpopulations in the biopsy and surgical specimens of breast
carcinomas by routine morphological diagnostics; to determine by means of Background & Objectives: Elevated peptidyl arginine deiminase type 4
immunohistochemistry if the amount of tissue material is adequate for a (PAD-4) enzyme activity in breast cancer is a well-documented fact, but
reliable study of tumour-filtering lymphocytes (TILs) in breast carcinoma. little is known in connection with molecular – genetic subtypes of breast
Methods: The object of the study was trepanobiopsy specimens and carcinoma.
surgical material taken from 60 patients with breast carcinoma with ma- Methods: PAD-4 level was determined in serum samples of 98 women
lignancy of various degrees (from G1 to G3). In the surgical material, the with primary breast cancer in period January 2017 – april 2018. They
central zone of the tumour and the zone of active tumour growth were divided in 5 subgroups based on standart IHC data: group 1 –
(peritumoural) were evaluated and compared with the biopsy specimen luminal A cancer, 2 - luminal B Her-2 negative, 3 - luminal B Her-2
(one tissue sample was taken). Subpopulations of T and B lymphocytes positive, 4 - non-luminal Her-2 positive, 5 - triple negative cancer.
were investigated immunohistochemically using CD4 (Clone 4B12) Samples were obtained before initiation of any oncologic treatment and
(Dako), CD8 (Clone SP57) (Ventana), CD56 (Clone 123С3) (Ventana). in 41 cases again 15-24 days after definitive surgery. Also 20 samples
Results: The study showed that regardless of the tumour malignancy degree, were taken from 20 healthy women. PAD-4 level was determined with
a significantly smaller number of CD4 positive T-lymphocytes and CD56 Human PAD-4 ELISA Kit n automatic analyser ADALTIS Personal
positive natural killer cells was observed in the surgical material and biopsy LAB. Statistical analysis performed by means of IBM SPSS Statistics 19.
specimens taken from central and peritumoural zones of breast carcinomas. Results: Median PAD-4 level before treatment was 9,0 ng/ml, with the
The representation of CD8 positive T-cytotoxic lymphocytes in all studied same 9,0 ng/ml median level after surgery. Median enzyme levels for
groups was comparably identical both in the biopsy specimens and in the cancer subgroups were as follows: group 1 - 11,05 ng/ml., group 2 -
surgical material, regardless of tumour malignancy degree. 11,9 ng/ml., group 3 -10,8 ng/ml., group 4 - 7,99 ng/ml., group 5 - 9,9
Conclusion: To assess the representation of CD8 positive T-cytotoxic lym- ng/ml. Median PAD-4 level for healthy women was 1,5 ng/ml (Q1=0,0;
phocytes in breast carcinomas, one standard core biopsy specimen is sufficient, Q3=2,0) ng/ml, which is significantly different from cancer group ( Mann
regardless of tumour malignancy degree. To assess the infiltration of CD4, –Whitney U test, U=38,500, p<0,001).
CD56 by positive breast carcinoma lymphocytes correctly, comparable to the Conclusion: PAD-4 level was higher in luminal cancer, but further re-
surgical material, more samples are required, one specimen is not enough. search is needed to make definitive conclusions.

E-PS-02-012 E-PS-02-014
Primary leiomyosarcoma of the breast: a rare case report Breast cancer subtypes - single institution results of 11754 consecu-
P. Tziakou1, V. Papamichail2, E. Delliou3, A. Zizi-Sermpetzoglou1 tive cases
1
Department of Pathology of Tzaneio General Hospital of Piraeus, P. Drev2, O. Blatnik2, J. Blazina2, J.A. Bandres Contreras2, G. Gasljevic1,
Greece, 2 Laboratory of Pathology "ISTODOMI" - Piraeus, Greece, M. Gjidera2, B. Grcar Kuzmanov2, A. Klevisar Ivancic2, S. Pavlovic2,
3
Laboratory of Pathology - Xanthi, Greece B. Gazic2
Virchows Arch

1
Department of Pathology, Institute of Oncology Ljubljana, Slovenia, E-PS-02-016
2
Institute of Oncology Ljubljana, Slovenia No special type invasive breast carcinoma transformed to metaplastic
carcinoma after neoadjuvant chemotherapy
Background & Objectives: Invasive breast carcinoma (IBC) is a heter- G. Kir1, Z.C. Olgun1, O. Alimoglu2
1
ogenous disease consisting of a number of subtypes with different prog- Istanbul Medeniyet University, Department of Pathology, Turkey,
2
nostic and predictive characteristics. Assessment of breast carcinoma Istanbul Medeniyet University, Department of General Surgery, Turkey
subtypes (BCS) is a crucial factor for management of IBC. Published
large-series, long-term, single-institution data on observed frequencies Background & Objectives: Metaplastic breast carcinoma is a rare and
of BCS are scarce. aggressive type of breast carcinoma. Here, we report a case of metaplastic
Methods: Institutional database was searched for IBCs in the pe- breast carcinoma which transformed from Invasive Breast Carcinoma, No
riod 2006-2018. BCS were classified using molecular tumour bio- Special Type (NST) following neoadjuvant chemotherapy (NAC).
markers. ER and PR were assessed immunohistochemically. Cut- Methods: 46 year-old woman presented with a palpable mass which was
off was 1%. HER2 was assessed with both IHC and FISH. Cut-off diagnosed with tru cut biopsy as invasive breast carcinoma, NST. The
set according to valid ASCO guidelines. IHC and FISH protocols patient received 4 cycles of NAC with anthracyclin and taxane
were EQA monitored. Analysis was performed to obtain data (av- Results: The patient underwent a segmental mastectomy after NAC.
erage and annual variation) on predictive factors (PF) ER, PR, HR, Microscopically the tumour was arranged in a diffuse pattern.
HER2 and BCS. Tumour cells had large vesicular, irregular nuclei with prominent
Results: 11754 consecutive IBC were identified. PF results:87.3% ER, nucleoli and abundant cyoplasm. Necrosis was detected in large
75.6% PR, 87.7% HR and 13.3% HER2 positive. BCS results: 78.3% areas. The neoplastic cells of the excised tumour were estrogen
luminal-A, 9.3% luminal-B, 3.9% HER2-positive and 8.5% triple- receptor (ER), progesterone receptor (PR), and HER-2 negative
negative (TN). Annual variation was minimal in all PF and BCS, however whereas on previous biopsy tumour cells were diffusely positive
there is a slight increase in both luminal subtypes and a slight decrease in for ER and PR and negative for HER-2. After NAC tumour showed
HER2-positive and TN. diffuse positivity for EGFR and vimentin, scattered cells stained
Conclusion: Observed proportions of luminal A (78.3%) and B with P63 and HMWCK. EMA was patchy and weakly positive at
(9,3%) subtypes are in line with latest reports but slightly higher neoplastic cells. Tumour was negative for PANCK, CAM 5.2,
compared to majority of reports, while proportions of HER2- Cytokeratin 5/6, Cytokeratin 14, and CD34. So the tumour was
positive (3,9%) and TN (8,5%) are slightly lower compared to consistent with metaplastic carcinoma.
reported values. Conclusion: Immunhistochemical changes after NAC is not an uncom-
Observed slight increase of frequencies of luminal subtypes and decrease mon finding but morphologic transformation is very rare entitiy. This is
in HER2-positive and TN are in line with recently published population the third case of transformation to metaplastic carcinoma after NAC as far
studies that show increasing incidence of ER-positive and decreasing as we know from English literature.
incidence of ER-negative IBC.

E-PS-02-017
E-PS-02-015 The distribution of morphomolecular subtypes of breast cancer in pa-
In situ lobular carcinoma involving the sclerosing adenosis: a report tients who recieved neoadjuvant therapy and breast-conserving surgery
of two case M. Urezkova1, A. Kudaybergenova1, E. Turkevich1, V. Klimashevsky1,
G. Kir1, H. Gunel1, A. Aydin1 P. Krivorotko1
1 1
Istanbul Medeniyet University, Department of Pathology, Turkey N.N. Petrov National Medical Research Center of Oncology, Russia

Background & Objectives: Sclerosing adenosis is a common lesion in Background & Objectives: Beginning with the B-14 NSAB study,
the breast. Sclerosing adenosis may rarely contain lobuler carcinoma in the concept of neoadjuvant (pre-operative) therapy for breast cancer
situ (LCIS) foci and may cause diagnostic challenge. is in common use with oncologists. According to P. Cortazar, the
Methods: We report the first case of a 44-year-old premenopaus- frequency of pre-operative therapy is up to 80% in different biolog-
al women and the second case of a 55-year-old postmenopausal ical subtypes. The aim of our study is to determine the proportion of
women, both presented with breast pain. On ultrasonography of BCS after pre-operative therapy, distribution of biological subtypes
the fırst case demonstrated a 8 mm solid isoechoic mass which in this patients and proportion cases achieved complete pathological
is a well contoured lesion including milimetric calcification. The response (pCR).
second patient’s ultrasonography showed a 12 mm solid Methods: The study included 1016 cases of breast cancer treated with
hypoechoic noduler lesion. Both mammographies were unre- neoadjuvant therapy and subsequent surgery in our center in 2013-2018.
markable (BIRADS 0). The patients underwent core-needle Results: BCS after neoadjuvant therapy was 206 cases (20,2% of patients
biopsy. treated with neoadjuvant therapy and 16% of BCS in total). The distribu-
Results: On the microscopic evaluation of both cases revealed tion of biological subtypes in the group of patients receiving neoadjuvant
stromal fibrosis and expanding solid tubules which preserved lob- therapy and BCS:
ular architecture.LCIS morphology was seen in most of the tu-
bules. The dyscohesive cells in this tubules were uniform with & “All luminal subtypes”- 119 (57.7%);
peripheral round nuclei. On immunohistochemical analysis, & “HER2-positive”- 21 (10%);
myoepithelial cells were observed with p63, CK14, E-kadherin & “Triple-negative (TNBC)” - 58 (28%);
and β- catenin stains. E kadherin and β-catenin staining were lost
in the epithelial cells filling the tubulus. Diffuse ER and PR
In the BCS group pCR was recorded in 23% of cases. Distribution in this
expression were observed. The diagnosis were consistant whit
group:
lobular carcinoma in situ involving the sclerosing adenosis.
Conclusion: The presence of LCIS in sclerosing adenosis is rare & “All luminal subtypes” – 13 (27%);
and may be misdiagnosed as invasive mammary carcinoma. & “HER2-positive” – 10 (20,8%);
Immunohistochemical staining may be used to resolve this
& “TNBC” – 25 (52,2%).
confusion.
 Virchows Arch

Conclusion: The proportion of BCS after neoadjuvant therapy in our Methods: Data was extracted from pathology report of our institutional
study is significantly less than that described in international studies nev- pathology files after an extensive systematic retrieval from the laboratory
ertheless in TNBC we achieved maximal response to pre-operative ther- informatics system on patients subjected to breast biopsies (including
apy and can avoid surgery as option for this group. core biopsies) and resection specimens from the last 10 years.
Results: 37 women subjected to breast biopsy or resection were retrospec-
tively reviewed from our institutional pathology files. 32 (89%) were biopsy
E-PS-02-018 specimens, while 5 (11%) were resection; 17 were located on the right breast
Androgen receptor expression in non-metastatic breast cancer: has it (46%) and 20 on the left (54%). Superior quadrants (24, 65%) were followed
go any prognostic and predictive value? by retroareolar (14%) and other breast regions. Clear steatonecrosis criteria
D. Lokuhetty1, B.I. Ruiz2, H. Wijesinghe3, V. White2, I. Cree1 was evidenced in 9 cases (24%), calcifications, including distrophic and
1
International Agency for Research on Cancer, France, 2 IARC/WHO, microcalcifications, were evidenced in 11 cases (30%). Other findings report-
France, 3 University of Colombo, Sri Lanka ed were usual ductal hyperplasia (2), atypical ductal hyperplasia (1), collunar
cell changes (3) and pseudoangiomatous stromal hyperplasia and
Background & Objectives: Androgen receptor (AR) is emerging as an fibroadenomatoid changes (2). In a subgroup analysis, microcalcification
useful prognostic and predictive marker in breast carcinoma (BCa). was statistically distinct from other grouped features (p= 0.004, IC (-0.799 -
Evidence points towards different AR signalling pathways in molecular -0.221)). Special stains were performed and resulted negative.
BCa subtypes with different oncogenic roles. Several studies document Conclusion: XM is an exclusion diagnosis, usually directly made after
AR to have prognostic value in early, non-metastatic BCa, but subtype is special stains result negative. In this series, the presence of a
less evaluated. The predictive role of AR for targeted therapy has not been microcalcification group associated to XM in biopsies performed to ex-
evaluated extensively. clude malignant microcalcifications reveals that this diagnosis should be
This systematic review protocol plans to summarize the prognostic and considered more often as a differential in the breast microcalcifications
predictive value of AR expression in non-metastatic breast cancer. workup. We have presented a summary of findings for XM and reviewed
Methods: Electronic databases (PubMed, EMBASE, Cochrane the most common associated findings, especially the association to
Library, WOS) will be searched. Data base specific search terms microcalcifications, suggesting the important of relying in this differential
related to the review question, such as “breast neoplasm”, “androgen diagnosis during a microcalcifications workup.
receptors”, but also other expressions “breast cancer”or “AR expres-
sion” will be combined into a tailored search strategy that will in-
clude all references from 1980 to March 2019 in English, Spanish, E-PS-02-023
German or French. Studies will be included if they analyse the rela- New about the "natural history of cancer"
tion between the AR and its prognostic or predictive value in women V. Danilenko1, V. Onufrieva1, A. Filin1
1
with non-metastatic breast cancer, reporting on outcome measures, Voronezh State Medical University named after N.N. Burdenko,
such as overall survival, disease free survival, progression free sur- Department of Pathological Anatomy, Voronezh, Russia
vival or median survival.
Results: Results will be screened by two independent reviewers and the Background & Objectives: The aim of the study was to clarify ideas
initial selection full-text assessed applying eligibility criteria. Data from about the «natural history of cancer», particularly breast cancer.
included papers will be extracted into standardised forms including par- Methods: 765 cases of surgical material of breast cancer were studied
ticipant and prognostic factor information, outcomes and effect size. Risk (protocols of gross-descriptions and microslides). The dynamics of
of bias of studies will be assessed using the Quality Prognostic Studies changes in the tumour volume were determined.
tool and quantitative synthesis of results performed. A narrative synthesis Results: The average volume of breast cancer nodes in five decades of
of results will include description of strength and consistency of out- women's lives did not differ significantly. Similar was the frequency of
comes, as well as the methodological quality of the studies. occurrence of nodes with cancer-stages double the volume (<1cm3
Conclusion: This review will synthesize available evidence for the ~2sm3, ~4sm3, ~8sm3, >8sm3). By fluctuating in the zone of small vol-
prognostic and predictive value of AR expression in non-metastatic umes, the cancer nodes reached stable maximum in the region of linear
BCa considering subtypes. Research gaps will be identified and dimensions of about 2.5 cm (>8 cm3).
recommendations drafted. The results will update to the 5th series Conclusion: The obtained data shows that the nodes of breast cancer
of WHO Classification of Tumours. Review title will be registered grow unevenly, sharply slowing the growth rate as its volume increases.
and protocol will made available. Hence, the single data on the doubling of the volume of specific nodes of
breast cancer for some time intervals cannot be extrapolated to the entire
«natural history of cancer», as it was postulated before.
E-PS-02-022
Suspicious microcalcifications associated to Xanthogranulomatous
Mastitis E-PS-02-024
L. Campos Clemente1, L. de Medeiros Reis1, M.L. Balancin1, M. Profile of Adenoid Cystic Carcinoma (ACC) of the breast: A 17 year-
Abrantes Giannotti1 histopathological review of 13 cases
1
Department of Pathology, University of Sao Paulo, Brazil L.L. Sousa Veras1, M. Alvares Leão1, A. Uema Watanabi1, N. Soares de
Menezes2,1
1
Background & Objectives: Xantogranulomatous Mastitis (XM) is Barretos Cancer Hospital, Brazil, 2 European Society of Pathology,
benign, usually self-limited inflammatory condition of the breast. Brazil
No clear etiology has been established, electing it as an exclusion
diagnosis: special stains and cultures should be negative and differ- Background & Objectives: Adenoid cystic carcinoma (ACC) of the
entials as histiocytic diseases should be excluded, as well as malig- breast is a rare subtype. It occurs in less than 0.1% of patients with breast
nancy. In this series we have reported a cohort of XM cases and cancer. The objective of this study was to determine the clinical, histo-
evidenced a distinct group of calcification-associated XM. The main logical and immunohistochemical features of these tumours.
objectives of this study were to build an exploratory case series on Methods: A retrospective review between January 2002 and March 2019
XM cases from a Brazilian Cohort of patients and describe associ- was performed using the cancer registry database in a single reference
ated findings. center for cancer treatment in Brazil.
Virchows Arch

Results: Thirteen patients were diagnosed with ACC. The mean age of Background & Objectives: Immunohistochemical (IHC) stain of Ki67
the patients was 63.8 years (52-87 years). There was only one male is a prognostic and predictive marker in breast cancer (BC). However,
patient. Only 3 patients reported a familial history of breast cancer. manual scoring (MS) is semiquantitative at best and suffers from high
There was one case of intraductal carcinoma in the contralateral breast. inter-observer variability which limits its clinical value.
The size of tumour ranged from 2.0 to 7.5cm. 46% of the patients Methods: We developed an innovative digital image analysis (DIA)
underwent mastectomy with sentinel lymph node biopsy. The nodal sta- workflow which uses sequential Ki67 and cytokeratin (for precise auto-
tus was positive in just one case. All cases were HER-2 negative. There matic tumour cells recognition) IHC staining on the same section. Ki67
was only one case in which estrogen and progesterone receptors were proliferation index was determined by DIA and MS in 4 tissue microar-
positive. Follow-up was done in 53% of patients with 85% patients being rays containing 257 breast cancer tissue cores divided in training (n=140,
free of disease in the last follow-up. There was only one case of distant HR+) and test (n=117, HER2+ and TNBC) sets. Agreement between DIA
metastasis for the lung. and MS was calculated using intraclass correlation coefficient (ICC) and
Conclusion: Adenoid cystic carcinoma is a rare special subtype of breast Bland-Altman (BA) plot.
cancer with good prognosis despite being a triple-negative tumour. Results: In the training set, 124 and 121 cores were evaluable for DIA
Program of Assistance and Incentive to the Researcher (PAIP) - Pio XII and MS, respectively. ICCs were 0.928 and 0.807, depending if a
Foundation, Barretos, SP cytokeratin mask was used or not. When applied to the test set (115
evaluable cores for DIA and 100 for MS), ICCs were 0.821 with mask
and 0.727 without the mask. BA plot revealed that the distance between
E-PS-02-025 DIA and MS increased with the magnitude of Ki67 measurement and
HER positivity in breast cancer is not associated with Ki67 of <5% positively correlated with analysed tumour area.
and 50% of HER2 positive breast cancer are PR negative Conclusion: Sequential multiplex IHC combined with DIA represent
S. Javidparisijani1, I. Kim1, S. Pambuccian2, P. Tang1 a valid alternative to MS for Ki67 measurement. The observed in-
1
Loyola University Medical Center, USA, 2 Loyola Univeristy Medical crease in difference between the two methodologies with increasing
Center, USA Ki67 values does not directly impact on clinically relevant thresh-
olds, but points to the poor quantitative nature of MS. Additional data
Background & Objectives: HER2 over-expression or amplification is a on DIA reproducibility and agreements across different cut-offs will
poor prognostic factor for breast cancer, It has been suggested to associate be presented.
with younger patients, higher grades and higher Ki67 expression.
ASCO/CAP guidelines recommend all primary breast cancer being tested
for HER2 by either IHC or FISH as the primary test, and reflexed to the E-PS-02-027
other test if IHC is equivocal (2+) or FISH is inconclusive. It has been our Lymphoepithelioma-like carcinoma of the breast: a case report
institutional policy that all HER2 IHC 1+ to 3+ cases reflexed to FISH C. Gkogkou1, E. Baliou1, E. Koniaris1, E. Gioti1, E. Moula1, G. Kafiri1
1
analysis. Taking the advantage of our available data set, we investigated "Hippokratio" General Hospital of Athens, Greece
the relationship between HER2 positivity and these clinico-pathological
features, and with a focus on Ki67 and PR expression levels. Background & Objectives: Lymphoepithelioma-like carcinoma
Methods: We have reviewed our archival data for primary breast cancer (LELC) is an exceptionally rare tumour of the breast with only a few
between Jan 2015 and June 2018, and identified 278 cases with both HER2 cases reported in the literature. It mimics its nasopharyngeal counterpart
IHC and FISH analysis. The clinico-pathologic features including patient and its possible correlation to HPV is still being investigated.
age, histologic type, histologic grade, and expression of ER, PR and Ki-67 Here we present a case of LELC of the breast because of its rarity and the
were documented, and the evaluation of positive HER2 with tumour grade, diagnostic challenges it poses on histological level.
patient age, and ER, PR and Ki67 expression were conducted. Methods: A 57 year-old woman presented with a tumour located in the left
Results: Among the 278 cases studied, 71 cases are HER2 positive, included breast. Lumpectomy was performed and the surgical specimen was submit-
3%, 31% and 66% as grade 1, 2, and 3 tumours, respectively; and 4%, 41% ted for histological examination. Sectioning of the excised specimen revealed
and 55% of tumours are in <40 years of age, 40-60 years of age, and >60 a white, solid, firm tumour measuring 1.6cm and irregular, stellate border.
years of age groups, respectively. 1) As in relation to Ki-67 expression levels Results: Microscopically the tumour was composed of large cells with
(<5%; 5-10%, 11-20%; and >20%), no tumour with <5% Ki67 expression eosinophilic cytoplasm and pale stained nuclei with prominent nucleoli.
has positive HER2 regardless of its histologic grade. 2) HER2 positivity is The cells were arranged in solid nests and small trabeculae, separated by a
noted in between 5-11% in ER negative and 44-57% in PR negative Grade 2 dense inflammatory infiltrate, composed of small lymphocytes.
and grade 3 tumours. 3) There is no significant age difference among different Lymphoid follicles were also evident. The periphery of the tumour was
age groups noted between HER2 positive and HER2 negative tumours, even frankly invasive and no syncytial growth pattern was observed. There
within the same histologic grade. was no evidence of necrosis. Mitotic activity was increased. Neoplastic
Conclusion: Ki-67 expression of <5% is not associated with HER2 pos- cells were immunoreactive for CK8/18 and e-Cadherin. They didn’t stain
itive; and over 50% of HER2 positive tumours are PR negative. Larger for ER, PR and Her2. Ki-67 proliferation marker was positive in approx-
studies are warranted to confirm these finding; so it could provide guid- imately 30% of the malignant cells.
ance to pathologists in perform HER2 reflex test. Based on the above findings, the diagnosis of LELC was established.
Conclusion: The main differential diagnosis of LELC of the breast is
medullary carcinoma. The lack of circumscription and the absence of
E-PS-02-026 syncytial growth pattern will aid to the correct diagnosis. Pathologist
Sequential multiplex immunohistochemistry and virtual image re- awareness is required to avoid possible diagnostic pitfalls.
construction using a single slide for quantitative Ki67 proliferation
index measurement in breast cancer: method development and
validation E-PS-02-028
G. Serna1, S. Simonetti1, R. Fasani1, F. Pagliuca2, P. Gallego1, L. Uncommon metastasis of invasive lobular breast cancer to the
Alonso1, X. Guardia1, J. Jimenez1, P. Nuciforo1 endometrium,an endometrial polyp, the cervix and a leimyoma: a
1
Molecular Oncology Group, Vall d'Hebron Institute of Oncology case report and review of the literature
(VHIO), Spain, 2 Department of Advanced Biomediacal Sciences, G. Benkhedda1, I. El Hafaia2
1
Pathology Unit, University of Naples "Federico II", Italy University Algiers, Algeria, 2 EHS Centre Pierre et Marie Curie, Algeria
 Virchows Arch

Background & Objectives: Although it is known that breast cancer can positive for both CD133 and ALDH1 expression. The expression of
metastasize to many organ sites, metastasis to the uterus is uncommon CD133 had a highly significant correlation with the grade of tumour
and usually occurs during widespread metastatic disease. Lobular carci- (p=0.0005). Increased expression was seen in grade 3 tumours.
noma is not the most common histological subtypes of breast carcinoma, Expression of ALDH1 had a significant correlation with the size of tu-
but it is the most frequent histologic type that causes gastrointestinal, mour (p=0.0005). Combined expression of CD133 and ALDH1 had a
ggynaecological and peritoneal metastases.When an extragenital tumour statistically significant correlation with the grade of tumour (p=.0005) and
metastasizes to the uterus, it is predominantly located in the myometrium; size of tumour(p=0.008).
in a minority of cases, the metastasis is confined to the endometrium. The Conclusion: In our study, we analysed the expression of CD133 and
main symptoms of the uterine metastasis depend on the anatomic involve- ALDH1 CSC markers in carcinoma breast. CD133 was significantly
ment site. Abnormal uterine bleeding is by far the most important symp- associated with increased tumour grade. There was significant correlation
tom. Uterine metastases account for approximately 4% of genital tract between ALDH1 expression and tumour size. In combination both the
metastases, with 47% of cases involving the breast as the primary site. markers correlated significantly with grade and size of the tumours.
Methods: A 50-year-old woman was complaining of postmenopausal Identification of cancer stem cells and early intervention with targeted
uterine bleeding and leucorrhea. Her medical history revealed that she therapy might be of clinical use for a better patient prognosis.
was diagnosed with breast carcinoma 4 years ago. At that time she
enderwent a radical mastectomy associated with axillary lymph node
dissection pathological examination of the tumour revealed Grade 3 in- E-PS-02-030
filtrating lobular carcinoma; stage IIIa (T2 N2 M0).A diagnostic work‑up Immunohistochemical evaluation of the possible prognostic signifi-
was initiated to detect possible causes of vaginal bleeding. She underwent cance of MTA-1 protein in breast cancer
transvaginal ultrasound, which revealed endometrial thickening (13 mm). M. Lambropoulou1, A. Maroudas1, V. Papadatou1, S. Tologkos1, O.
A hysteroscopic examination revealed an endometrial polyp in the uterine Pagonopoulou2, I. Balgkouranidou1, N. Xenidis3, G. Tripsianis4, L.
cavity, which was resected. The morphology and immunohistochemical Yorkas1, S. Meditskou5, N. Papadopoulos1
1
studies confirmed the diagnosis of metastasis of lobular breast carcinoma Histology-Embryology Lab., Medical Department, Democritus
to an endometrial polyp. University of Thrace, Greece, 2 Physiology Lab., Medical Department,
The patient then underwent a total abdominal hysterectomy with bilateral Democritus University of Thrace, Greece, 3 Dep. of Clinical Oncology,
salpingo‑oophorectomy and partial colectomy. Medical Department, Democritus University of Thrace, Greece,
4
Results: The hysterectomy measuring (8x5x4). The section slice showed Medical Statistics Lab., Medical Department, Democritus University of
an intramural leiomyoma measuring 3 cm. The cervix presents a white Thrace, Greece, 5 Histology-Embryology Lab., Medical Department,
thickening in some places. Aristotle University of Thessaloniki, Greece
Pathology results demonstrated that the endometrium,the uterine
leiomyoma and the cervix shared the same histopathological features as Background & Objectives: Breast cancer is the most common type of
those presented by the primary lobular breast carcinoma. cancer in women and the major type responsible for their mortality. For
Conclusion: Uterine metastases of breast cancer are very rare; the pres- that reason, new cancer prognostic biomarkers are being developed, such
ence of abnormal bleeding symptoms in a patient with a history of breast as the gene of MTA-1 protein. This particular protein belongs to the
cancer should be suggestive of endometrium metastatic disease especially metastasis associated proteins family (MTA) and is encoded by the cor-
in case of invasive lobular carcinoma. responding gene located on chromosome 14q32.33. High expression
The current review presents the second reported case of lobular breast levels of MTA-1 are observed in cases of tumours and its levels are
carcinoma metastasizing to an endometrial polyp, the cervix and a directly related to cancer aggression and the possibility of metastasis.
leiomyoma simultaneously. Expression of MTA-1 has been observed in various types of cancer, such
as liver, gastric and ovarian cancer. This research work aims at the im-
munohistochemical study of the expression of MTA-1 protein in breast
E-PS-02-029 cancer and its correlation with clinical-histopathological parameters.
Immunohistochemical analysis of cancer stem cell markers CD 133 Methods: We used 26 breast tissue specimens derived from patients with
and ALDH1 expression in carcinoma breast various cancer subtypes. Of these 26 patients 24 were women and 2 were
J. Kini1, K. Jeepalem1, H. Kini1, K. Sahu1 men. Indirect immunohistochemistry was performed, using anti-MTA-1
1
Department Of Pathology, Kasturba Medical College, Mangalore, antibody and the expression levels of MTA-1 were then tested and cor-
Manipal Academy of Higher Education, Manipal, Karnataka, India related with clinical-histopathological parameters.
Results: Positive expression of MTA-1 was observed in 20 of 26 patient
Background & Objectives: Carcinoma breast is the most commonly samples. Furthermore, the presence of lymph node metastases was cor-
diagnosed malignancy, accounting for 22% of all malignancies in wom- related with high MTA-1 levels with statistical significance (p <0.001).
en. In India, breast cancer ranks second to cervical cancer with increasing Conclusion: Based on the results of this study, we concluded that MTA-1
incidence in both developed and developing countries. Carcinoma breast protein is a potential effective prognostic marker for this disease and can
encompasses numerous histological sub-types with unique molecular fea- possibly be used as a therapeutic target. However, due to small sample
tures and therapeutic response. The aim of the study was to analyse and pool further investigation is required.
correlate the expression of cancer stem cell markers CD133 and ALDH1
in carcinoma breast with that of size, stage, grade of tumour, lympho-
vascular invasion and lymph node status. E-PS-02-031
Methods: Immunohistochemistry was performed with CD133 and Role of protein P66 SHCA in programs epithelial-mesenchimal tran-
ALDH1 on 130 retrospectively and prospectively collected cases of car- sition in invasive carcinoma of no special type
cinoma breast. The study samples included mastectomy specimens of T. Bezuglova 1 , A. Erzieva 1 , T. Bezuglova 1 , L. Kaktursky 1 , M.
breast cancer. Clinical details were retrieved from the case files. Mnikhovich1, A. Asaturova2, V. Kometiva3, I. Vasin4, S. Snegur4, K.
Histopathology findings and ER, PR, Her-2 neu status were noted. Bunkov4, D. Kushch5, N. Malyugin5
1
Results: A total of 53 cases (40.8%) stained positive for CD133 marker. Research Institute for Human Morphology, Russia, 2 FSBI 'National
Similarly, 30 cases stained positive for ALDH1. In the study, more than Center for Obstetrics, Gynaecology and Perinatology named after
half of the cases were negative for both CD133 and ALDH1 cancer stem V.I.Kulakov' Ministry of Healthcare Russian Federation, Russia, 3
cell markers (55.4%, n=72), whereas about 20% of the cases stained National Medical Research Center of Obsterics, Gynaecology and
Virchows Arch

Perinatalogy, Russia, 4 Ryazan Reginal Clinical Hospital, Russia, 5 a few cells. She was finally diagnosed as fibromatosis-like prolifera-
Pirogov Russian National Research Medical University (Moscow), tive lesion.
Russia Conclusion: To the best of our knowledge, this is the first case report of
tumour occurrence other than recurrence of carcinoma in omental flap.
Background & Objectives: Protein P66 SHCA can act as a sup- The diagnosis of the newly occurred lesion with positive staining of
pressor and stimulator of carcinogenesis in different types of cytokeratin in reactive fibroblasts in the harvested omentum was difficult
tumours.p66Shc is involved in the regulation of individual types because the possibility of breast cancer recurrence, especially
of cell death and it also participates in the pathogenesis of ma- fibromatosis-like metaplastic carcinoma should be ruled out.
lignant tumours..p66Shc is involved in the regulation of individual
types of cell death and it also participates in the pathogenesis of
malignant tumours. E-PS-02-033
Methods: Researched material of 35 patients with ICNst after rad- Elastic fibers in microenvironment of invasive ductal carcinomas of
ical mastectomy.30 patients (n =30) with metastases in regional breast
lymph nodes, liver, lungs and brain, 5 patients (n = 5) without S. Rjabceva1, I. Siamionik1, M. Derevyanko1
1
metastatic lesion. Age of patients was 35-85 years .Patients before Institute of Physiology of National Academy of Sciences of Belarus, Belarus
the operation did not receive neoadjuvant therapy. The diameter
of the tumour site is 0.8-4.0 cm. The degree of malignancy Background & Objectives: Collagen components in the tumour micro-
ICNST is G 2- G 3. The research was carried out by using light environment substantially influence cancer pathogenesis and progression.
microscopy and IHC method with the protein p66ShcA ( Abcam ) Nevertheless, status of elastic fibers and its prognostic role remain un-
and E-cadherin (Dako , LabVisionFlex)with a semi-quantitative clear. The aim of this study is to estimate the changes of stromal elastic
estimate. fibers in breast invasive ductal carcinoma.
Results: Expression ofp66ShcAproteinis higher in invasive carcinoma of Methods: Forty-seven slides from 42 female patients were investigated in
no special type (ICNST)with confirmed metastases (n= 30) in lymph this prospective study (median 1 slide/case). Histochemical studies for
nodes, liver and brain, than in breast cancer without metastases (n= 5). Russell-Movat pentachrome stain was done.
The severity of the cytoplasmic membrane expression was (+++) in the Results: The mean age of the patients was 66.5 (range 30-86). The mean
anaplastic component of tumours (epithelial-mesenchymaltransition of tumour size was 2.1 cm (range = 0.9-3.0 cm). 25 (59.5%) of the
zone), unlike fields with a more differentiated tumour component in par- patients had low grade cancer, 14 (33.3%) – medium grade and 3
allel with changes in expression of E-cadherin (reduced expression of (7.1%) of the patients had high grade. Lymph node metastases was de-
change, until complete disappearance). tected in 21 (50.0%) cases. Thickened elastic fibers was found in tumour
Conclusion: The high expression level of p66shccorrelateswith an tissue in 37/88.1% of patients: around vessels (37/88.1%), in stroma (24/
unfavourable prognosis for breast cancer, which was shown by us in 57.1%) and around ducts (15/35.7%). Gamma`s correlation analysis re-
the areas of invasive growth (epithelial-mesenchymaltransition zone) vealed the associations between an increasing of thickness of elastic fibers
innon-specificcarcinoma.Proteinp66ShcA is one of the first diagnostic around vessels and tumour grade (r=-0.35, p <0.05).
biomarkers for identifying malignant tumours with an unfavourable prog- Conclusion: This study showed that the change in the thickness of the
nosis and aggressive course, regardless of the molecular subtype. elastic fibers in breast invasive ductal carcinoma microenvironment is
related to tumour grade. Low grade breast carcinoma of no special type
characterised by formed of thickened elastic fibers around vessels often
E-PS-02-032 than high grade carcinoma.
Fibromatosis-like spindle cell lesion occurring after breast recon-
struction with omental flap: a case report
S.G. Song1, J.H. Moon1, M. Jung1, Y.J. Hwang1, J.H. Kim2, H.S. Ryu2, E-PS-02-034
I.A. Park2 Expression of oestrogen receptor, progesterone receptor, and HER2
1
Department of Pathol, Seoul National Univ. Hosp., Republic of Korea, between primary breast carcinomas and metastatic carcinomas to
2
Department of Pathology, Seoul National University College of Medicine, the lung
Republic of Korea H. Lee1, W. Han2, S. Im3, J.H. Kim4, H.S. Ryu4, I.A. Park4
1
Department of Pathology, Chungbuk National University College of
Background & Objectives: Recently, omental flap has been widely used Medicine, Republic of Korea, 2 Department of Surgery, Seoul National
as one of the autologous breast reconstruction methods after surgery. University College of Medicine, Republic of Korea, 3 Department of
Some complications related to omental flap were reported, including Internal Medicine, Seoul National University College of Medicine,
short-term regional problems and recurrence of breast cancer. Republic of Korea, 4 Department of Pathology, Seoul National
Methods: Here, we report a case of fibromatosis-like proliferative lesion University College of Medicine, Republic of Korea
in a patient with intraductal breast carcinoma who had a nipple-sparing
mastectomy and reconstruction with omental flap. Background & Objectives: Estrogen receptor (ER), progesterone
Results: The patient was a 54-year-old woman who was diagnosed receptor (PR), and HER2 are major immunohistochemical (IHC)
with metachronous intraductal carcinomas in the bilateral breasts. She markers of breast carcinoma. We analysed the difference of IHC
received breast-conserving surgery for the left breast and eight markers among primary breast carcinoma specimen without prior
months later, she undergone nipple-sparing mastectomy and immedi- chemotherapy (PBC1), post-neoadjuvant chemotherapy specimen
ate reconstruction using omental-flap for the right breast . Three of primary breast carcinoma (PBC2), and metastatic carcinoma
years later, she complained of palpable mass in reconstructed right to the lung (MCL).
breast. Needle biopsy of the mass revealed atypical spindle cells Methods: One hundred cases were selected in which paraffin blocks of
lesion showing focal positivity to cytokeratin in immunohistochemis- MCL and PBC1 and/or PBC2 were available. All PBC1, PBC2, and
try stain. She received total mastectomy under a suggestion of meta- MCL specimens were available in 31 cases. Expression of ER, PR, and
plastic carcinoma. However, the histologic analysis of the mastecto- HER2 was studied in the PBC1, PBC2, and MCL. McNemar test was
my specimen showed infiltrative bland-looking spindle cell prolifera- used for the changes of the markers among the groups.
tion resembling fibromatosis or nodular fasciitis and expressed β- Results: There was a tendency of loss of PR expression between PBC1
catenin in the nuclei. Cytokeratin expression was observed only in and MCL (p=0.095). This tendency was also shown between PBC1 and
 Virchows Arch

PBC2 (p=0.074). However, there was no difference between PBC2 and Here we report two cases of metastasis to the breast with primary origin in
MCL. Changes of ER and HER2 were not significant among the groups. the colon and lung.
Subtype was changed in seven of 87 cases (8.04%) between PBC1 and Methods: Patients presented with a firm palpable mass in the breast,
MCL, three of which were changed from luminal into triple negative and suspicious for neoplasia on image studies.
two of which were from HER2 and triple negative subtype. Three cases Biopsy reveled an invasive carcinoma, G3 solid pattern with necrosis in
showed differences in subtype among PBC1, PBC2, and MCL: Subtype one case, and an invasive carcinoma, G2 with papillary features on the
of PBC2 in these cases was all triple negative subtype. Subtype of MCL other, both triple negative.
was the same as PBC1 in one case and as PBC2 in two cases, respectively. No previous malignancy was known.
Conclusion: IHC studies for ER, PR, and HER2 should be assessed in Results: Specimens revealed well circumscribed tumours, with an unusu-
the resection specimen or metastatic lesion after neoadjuvant or adjuvant al morphology, and absence of in situ carcinoma and calcifications, what
chemotherapy for establishing the further treatment plans. made the pathologist suspect of metastasis.
Immunohistochemistry helped make the correct diagnosis: metastasis of
colon adenocarcinoma and metastasis of papillary lung carcinoma.
E-PS-02-035 Conclusion: Metastasis on extramammary carcinoma are rare in the breast.
Invasive cribriform carcinomas of the breast: histopathological and Some histological features help make the right diagnosis: unusual mor-
prognostic features phology, well-circumscribed lesion and absence of in situ carcinoma and
S. Demir1, A. Akder Sari1, B. Bolat Kucukzeybek1, S. Yigit1, D. Etit1, A. calcifications.
Yazici1, Y. Kucukzeybek2 Immunohistochemistry is particularly helpful, if no previous history of
1
Izmir Katip Celebi University Ataturk Training and Research Hospital, malignancy is known.
Department of Pathology, Turkey, 2 Izmir Katip Celebi University Making the right diagnosis is important as to avoid unnecessary proce-
Ataturk Training and Research Hospital, Department of Oncology, dures and treatment of these patients.
Turkey

Background & Objectives: Invasive cribriform carcinoma (ICC) is a E-PS-02-037

rare type of invasive breast cancer which has three histological forms: Immunohistochemical evaluation of stromal component of invasive
the pure invasive type (>90% of cribriform pattern); the invasive type, carcinoma of no special type (IC NST)
predominant invasive cribriform pattern accompanied by a component of T. Bezuglova1, V. Kometova2, M. Mnikhovich1, L. Kaktursky1, A.
tubular carcinoma; the mixed type (except tubular carcinoma). Our aim is Asaturova3, A. Erzieva1, I. Vasin4, S. Snegur4, K. Bunkov4, D. Kusch5,
to evaluate histopathological and prognostic features of ICC of the breast. N. Malyugin5, A. Romanov5
1
Methods: ICC of the breast diagnosed between 2008-2019 in our depart- Research Institute of Human Morphology (Moscow), Russia, 2 Institution
ment was included in our study. National Medical Research Center of Obstetrics, Gynaecology and
Results: The study population consisted of 40 female patients (n=16 pure- Perinatology Ministry of Healthcare of the Russian Federation (Moscow),
ICC and n=24 mixed-ICC). Invasive ductal carcinoma was the predominant Russia, 3 FSBI 'National Center for Obstetrics, Gynaecology and
accompanying component (n=18/24, 75%). No invasive type was identified. Perinatology named after V.I.Kulakov' Ministry of Healthcare Russian
The median age was 46,5 years (min43-max53) for pure ICC, and 59 years Federation, Russia, 4 Ryazan Reginal Clinical Hospital, Russia, 5 Pirogov
(min53-max65) for mixed-ICC. The median size of the tumour was 2 cm in Russian National Research Medical University (Moscow), Russia
both types. Low grade tumours were more frequent in pure-ICC (35.7% vs
%21) whereas high grade tumours were more common in mixed-ICC (17.4% Background & Objectives: We aimed to evaluate stromal component of
vs 7%). Lymph node metastases were present in 42.9% of pure-ICC and 50% invasive carcinoma of no special type (IC NST) using qualitative and
of mixed-ICC. All of the tumours were ER and PR positive. Of all tumours, quantitive immunohistochemical study.
only one case of mixed-ICC was positive for CERB-B2. Methods: We have assessed the post-operative specimens of 118 patients
Ki67-index was <14% in all tumours except for 6 cases of mixed-ICC and (aged 40-80 years with mean age of 61 year old) with IC NST. Expression
1 case of pure-ICC. The follow-up time for pure-ICC was 2 to 127 of smooth muscle actin, desmin, collagen IV and VEGF was studied.
months (with a median of 81 months), and no recurrences/progression Results: In invasive carcinomas of solid type basement membrane was
was identified. absent or disrupted, in scirrhus fragments of basement membrane were
Conclusion: Pure-ICC of the breast is a very rare type of breast carcino- absent. Vimentin expression in stroma manifested as presence of fine
ma, seen in younger patient population and has a very good prognosis. cytoplasmatic granules, as well as staining of cells’ membranes. Most
prominent smooth muscle actin expression was detected in invasive
scirrhus. Expression VEGF was present in all forms of breast cancer,
E-PS-02-036 although in scirrhus it was minimal and was present in 16,3% of all cases.
Metastasis of extramammary malignancies to the breast - report of For breast cancer there is a pronounced topographical and quantitive
two cases relations between expression of these markers and growth patterns, tu-
S. Foreid1, J. Lopes2,1, J.M. Dias1 mour grade and stages of progression; myofibroblast-like markers (actin,
1
Synlab Pathology Porto, Portugal, 2 Centro Hospitalar São João, vimentin) are not infrequently situated in the parenchyma and stroma.
Portugal Collagen IV expression are lowered. Desmoplastic changes in scirrhus
manifest with minimal expression of VEGF, other markers are expressed
Background & Objectives: Metastases of extramammary malignancies predominantly by stroma regardless to tumour stage.
to the breast are a rare event, representing about 0,2%-1,3% of all mam- Conclusion: Our results signify importance of further studies of tumour
mary malignancies. Excluding hematological malignancies, the number stroma.
drops well below 1%. The most common reported sites of origin include
lung, skin, stomach and ovary.
Due to the high frequency of primary breast cancer and the rarity of E-PS-02-039
metastasis of non-mammary cancers to the breast, a new palpable mass Cystic neutrophilic granulomatous mastitis - the importance of his-
in the breast is usually presumed to be a primary breast tumour. tological diagnosis
Recognition of a non-mammary breast metastasis is very important, as C. Dahlstedt-Ferreira1, R. Rosas1, D. Gonçalves1
1
treatment and prognosis is very different. Hospital Garcia de Orta, EPE, Portugal
Virchows Arch

Background & Objectives: Cystic Neutrophilic Granulomatous Mastitis carcinoma, ER positive but HER2 negative. The macrometastatic
(CNGM) is a rare breast pathology that is believed to arise from tumour deposits in the sentinel node however had a completely
Corynebacterium spp infection. We present a case of CNGM, a rare different morphology and resembled the DCIS as both expressed
disease that clinically is a cancer mimicker. HER2 receptor gene. All the other axillary nodes were negative.
Methods: A 48 year old woman, multiparous, presented with a mass on Radiological assessment of the right breast showed no
her right breast on January 2018 and was thus submitted to antibiotics, abnormality.
without resolution. A year later, she underwent a mammogram, breast Conclusion: The morphology of the macrometastatic sentinel node
ultrasound and magnetic resonance, revealing a mass on her right breast, was different from the Grade 1 IDC in the mastectomy, in fact it
highly suspicious for a malignant lesion. closely resembled the high grade DCIS and that’s why we la-
Results: The core needle biopsy revealed a stromal mixed inflammatory belled the IDC as an incidental finding. There is evidence of
infiltrate and numerous granulomas formed by epithelioid histiocytes, underestimation of invasive carcinoma on initial diagnosis in pa-
with cystic spaces on the inside, lined by a rim of neutrophils, with tients undergoing axillary node dissection for DCIS2. But there is
occasional multinucleated gigantic cells. In some cystic spaces we were no documentation about the possibility of high grade DCIS
able to identify gram positive bacilli. metastasising in the presence of small low grade focus of invasive
Conclusion: This mastitis is treated through surgical resection or lipo- cancer. This case is unusual and raises a challenge in the man-
philic antibiotics, and can take weeks or months to be fully resolved. agement of these patients.
Through this case report, we want to show the distinctive histologic
pattern of this rare entity, which is frequently highly suspicious for ma-
lignancy by radiology. E-PS-02-042
Solid papillary carcinoma of the breast: an unusual carcinoma in-
volving the breast
E-PS-02-040 R. Ayadi1, N. Boujelbene2, M. Driss2, L. Charfi2, I. Abbes2, H. Azaiez3,
Breast metastasis: clinicopathological study of 11 cases K. Mrad2, R. Doghri2
M. Mellouli1, M. Triki1, R. Kallel1, I. Saguem1, W. Ghribi1, T. Sallemi 1
Pathology Department, Military Hospital, Tunis, University of Tunis El
Boudawara1, S. Charfi1 Manar, Faculty of Medicine of Tunis, Tunisia, 2 Department of Pathology,
1
Department of Pathology, Habib Bourguiba Hospital, Sfax, Tunisia Salah Azaiez Institute, Tunisia, 3 Department of Pathology, Salah Azaïez
Institute, Tunis, Tunisia
Background & Objectives: Breast metastases are rare. They represent
0.4 to 6% of all breast cancers. Our aim is to discuss their clinicopatho- Background & Objectives: Solid papillary carcinoma of the breast
logical features. (SPCB), a newly defined entity, is defined as a "distinctive form of pap-
Methods: We report a retrospective survey of 12 cases of breast metas- illary carcinoma characterised by closely apposed expansive, cellular
tases diagnosed over a period of 23 years (1992—2016) in the department nodules." This uncommon tumour frequently demonstrates neuroendo-
of pathology of the university hospital of Sfax (Tunisia). crine differentiation. To date, a few cases have been reported in the
Results: The diagnosis was carried on a material of cytoponction in two literature.
cases, a needle biopsy in seven cases and a surgery specimen in three We aimed to report a new case of SPCB and to describe its histopatho-
cases. The primary tumours understood two cases of small cell non- logical and immunohistochemical features.
Hodgkin lymphoma, a case of nasopharyngeal carcinoma, a case of Methods: We report, a case of a 58-year-old female presented with a
retroauricular melanoma, a case of leiomyosarcoma, a case of uterine mass in the left breast.
choriocarcinoma, a case of rectal neuroendocrine carcinoma, a case of Results: A chirurgical biopsy was done and showed a well-
small cell lung carcinoma, three cases of gastric adenocarcinoma and one circumscribed proliferation typically composed of solid papillary
case of a hematological malignancy of underminated origin. All patients nodules.The diagnosis of SPCB was suggested. Based on these
were women with a middle age of 37 years. In only one case the mam- findings,a radical mastectomy with axillary lymph node excision
mary metastasis revealed the primary tumour. Clinically, the size average were performed.The gross specimen identified a circumscribed tu-
of tumours was 2.9 cm. Bilateral mammary involvement was noted in mour measuring 15 mm with predominantly solid components.
three cases. Microscopy showed solid encapsulated tumour, with well-defined
Conclusion: A confrontation of clinical and pathological data with im- pushing borders, arranged in lobules with compactly arranged pap-
munohistochemical study is recommended for an accurate diagnosis of illary fronds and branching networks of the fibrovascular cores.The
breast metastasis. tumour cells were bland-looking with low-grade atypia and few
mitoses (< 5/10 HPF). On immunohistochemistry, tumour cells
are positive for synaptophysin and negative for chromogranin and
E-PS-02-041 CD56. P63, a myoepithelial cell marker, is negative along the
Unexpected metastatic axillary node in a high grade DCIS epithelial-stromal interface of the tumour.The final diagnosis of
S. Khalid1, M.W.A. Mangat1, A. Arnaout1 SPCB was established.
1
St George's University Hospital NHS Foundation Trust, United Kingdom Conclusion: SPCB is an unusual entity with distinctive clinicopatholog-
ical features and an excellent prognosis.It should be distinguished from
Background & Objectives: Axillary node metastasis in pure DCIS is conventional breast carcinoma to avoid over-treatment.
rare and has been reported in literature varying from 2-13%1.
Methods: A 68 year old female, known to have an intermediate grade
DCIS on the right breast treated by complete wide local excision two E-PS-02-043
years ago, was found to have calcifications on the left breast. The biopsy Clinicopathological and genetic risk factors of regional metastasis in
showed high grade DCIS. She underwent left mastectomy and Sentinel breast cancer patients
Lymph Node Biopsy (SLNB). The frozen section of the SLN showed a V. Kometova1, O. Bourmenskaya1, M. Rodionova1, M. Dardyk1, Y.
16mm macrometastatic tumour deposit. Dergunova2, P. Borovikov1, I. Balashov1, V. Rodionov1
1
Results: Despite extensive sampling, sections from the left breast National Medical Research Center of Obstetrics, Gynaecology and
revealed an intermediate to high grade DCIS (ER and HER2 Perinatology named after acamician V.I.Kulakov, Russia, 2 Ulyanovs
positive) and a 4.5mm focus of Grade 1 invasive ductal Regional Clinical Oncological Center, Russia
 Virchows Arch

Background & Objectives: In 60–70% of breast cancer patients in- E-PS-02-045

vasive axilla surgery appears to be unnecessary as pathology exam- Male breast carcinoma in a Romanian series of cases
ination reveals no regional metastases. The aim of our study was to O.C. Voinea1, A. Dumitru2,3,4, T. Georgescu2,3,4, M. Sajin2,3,4
1
identify the predictors of lymph node involvement in breast cancer CCSMM, Romania, 2 SUUB, Romania, 3 UMF Carol Davila, Romania,
4
patients according to clinicopathological and genetic features of the European Society of Pathology, Romania
primary tumour, which could help to avoid unnecessary lymph node
dissection. Background & Objectives: Breast malignancies are the most
Methods: Pathological reports of 175 breast cancer patients who important generators of morbidity and mortality among women
underwent breast surgery in V.I.Kulakov RC for OGaP were retro- worldwide. Considering its frequency, impresive advances in di-
spectively reviewed. Univariate analysis and multivariate logistic agnostic and therapeutic options were made. Being sporadic
regression were used to analyse the correlation between lymph node among male’s oncologic lesions, no standardised protocol exists,
metastasis and clinicopathological and molecular characteristics of either for diagnostic, follow up or treatment. All these aspects are
the primary tumour. The included patient age, multi/unifocal borrowed from pathology and oncology guidelines dedicated to
growth, laterality and quadrant localization, tumour size, histologi- female breast cancer. Since the importance of hormonal expres-
cal type, grade, Integrated Pathological Index (IPI), number of sion in this type of lesions is universally recognized, we believe
resected lymph nodes, ER- and PR-status, HER2-status, Ki67 index, that male breast lesions, taking into account it’s much worst prog-
molecular subtypes and 48 genes. nostic and stage at presentation than in women, deserves further
Results: Tumour size (p=0.0026), IPI (p‹0.001), CCND1 (p=0.021), studies for a superior approach.
SCGB2A2 (p=0.022), FOXA1 (p=0.025), FGFR4 (p=0.027), AR Methods: We present our experience with male breast cancers in a retro-
(p=0.048), PTEN (p=0.049), TMEM45B (p=0.049), CCNE1 spective review series of cases from Pathology Department of University
(p=0.05) were the most powerful predictors of axillary lymph node Emergency Hospital Bucharest. Histopathological examination was com-
metastases. There was no statistically significant correlation be- pleted with clinical information and the immunohistochemical expression
tween regional lymph node metastasis and age, tumour localization, of several markers was assed.
molecular subtypes, hormone receptor- and HER2-status and other Results: We identified 6 male breast carcinomas, four of which
40 genes. Multivariate logistic regression of significant variables were encountered in 5th, 6th and 7th decade and the other 2 in young
was used to create a nomogram. adults (35 and 40 years old). In a single case 2 different breast
Conclusion: Size of the primary tumour, IPI and 8 genes (CCND1, carcinoma histotypes were found. All of them were G2, with
SCGB2A2, FOXA1, FGFR4, AR, PTEN, TMEM45B, CCNE1) are in- tumoural stages varying between IB to IV. Several hormonal recep-
dependent predictive risk factors of axillary metastasis in breast cancer. tors, Ki 67 and HER2 were tested and expressed in each case, in
different percentages.
This work was sponsored by grants from the National Natural Science Conclusion: Male breast carcinoma is a rare entity with a poor
Foundation of Russia (АААА-А18-118053190016-7). prognostic, with a diffuse and profound invasion of adjacent struc-
tures, with a high expression of hormone receptors and with no
histologic relation to gynecomastia, considering that no associated
E-PS-02-044 benign lesions were found.
Mucoepidermoid carcinoma of the breast with MAML2 gene rear-
rangement: a case report
D. Gigliano1, M. Farinha1, J. Vieira1, N. Coimbra1, C. Leal1 E-PS-02-046
1
IPO-Porto, Portugal Characterisation of fluorescence signals chromosome 17 centromere
in epithelial cell breast ducts
Background & Objectives: Mucoepidermoid carcinomas (MEC) are the D. Chuglova1, A. Murashkina1, A. Kudaybergenova1, V. Kushnarev1
1
most common malignant neoplasms of both major and minor salivary N.N. Petrov National Medical Research Center of Oncology,
glands. Occasionally, they may occur in other sites such as lacrimal Russia
glands, thyroid and, very rarely, breast tissue, with less than 40 cases of
breast MEC described in literature. Given their rarity, grading and man- Background & Objectives: Normal epithelial cells used as inter-
agement are frequently controversial. nal control for HER2 in situ hybridization tests for its validity.
Methods: We report the case of a 15-years-old female with long-standing This study aimed to investigate the morphology of nucleus and
serosanguineous nipple discharge and a 9mm hypoechoic breast nodule fluorescent signals of chromosome 17 centromere (CEP17) in ad-
detected by ultrasound. The core biopsy of the nodule, performed in an- jacent to invasive carcinoma breast ducts in patients with interme-
other hospital, resulted in a diagnosis of invasive carcinoma, with features diate (2+) HER2 cases.
of secretory carcinoma. Once transferred to our Institution, an MRI scan Methods: We randomly selected 5 cases of invasive breast cancer
detected a smaller additional nodule. A second core biopsy was performed without any treatment with non-cancer adjacent ducts on slides
in this smaller nodule, while the slides from the first biopsy were reviewed. and performed fluorescent in situ hybridization (FISH) assay for
Results: The morphological features of the two nodules were overlap- HER2 amplification. Slides were scanned by Pannoramic 250
ping, both being evocative of salivary gland-like breast carcinomas. Our (3D Histech) and were assessed by manual tool selection of
main diagnostic hypotheses were MEC and secretory carcinoma. nuclei and fluorescence signals by annotations on whole slide
Immunohistochemical characterization revealed a ER-, PR-, HER2-, images.
p63+, CK14+ and CK5/6+ phenotype. FISH analysis revealed Results: We quantified 200 non-overlapping nuclei. Mean area of non-
MAML2 gene rearrangement in 76% of the cells, while no translocations cancer nuclei by DAPI was 46,25± 11,5 μm2 (compare 78,4±.16,08 μm2
involving the ETV6 gene were found. Based on these findings, a diagno- in cancer cells). Distribution of the fluorescent signals from HER2 gene
sis of low-grade MEC was rendered. Three years after conservative sur- and CEP17 in non-tumour breast duct epithelium were to red signal: 1,9
gery, the patient is healthy and disease-free. ±0,4; to green signal: 2,1±0,3.
Conclusion: MEC of the breast is an exceedingly rare neoplasm with Conclusion: Normal distribution of CEP17 and parameters of fluorescent
distinct morphological and molecular features. Genetic studies, along signals of gene HER2 is a key feature for analysis of diagnostic test.
with morphology and immunohistochemistry, are an essential aid in the Pathologist has to know basic morphological parameters of probe and
differential diagnosis of salivary gland-like breast carcinomas. nuclei.
Virchows Arch

E-PS-02-047 Results: Histologically, the tumour was constituted by a prolifera-

Programmed death-ligand 1 expression in triple negative breast tion of myoepithelial cells, surrounding small epithelial ducts, and
cancer presented paucicellar estroma. The myoepithelial cells were cuboid,
M. Bogdanovska Todorovska1, G. Petrushevska1, V. Janevska1, L. with abundant, clear and foamy cytoplasm, bulky nuclei with fine
Spasevska1, S. Kostadinova Kunovska1, R. Jovanovic1, B. Krsteska1, chromatin and small nucleolus. About 12 mitoses / 10 large magni-
A. Eftimov2, S. Komina1, P. Zdravkovski1 fication fields were documented, essentially in the myoepithelial
1
Institute of Pathology, Medical Faculty, Skopje, Assistant professor, component. No significant atypia, infiltrative growth pattern,
Republic of North Macedonia, 2 Pharmacist/ Institute of Pathology, desmoplasia or necrosis was identified.
Medical Faculty, Skopje, Republic of North Macedonia Conclusion: Adenomyoepitelioma is a relatively rare benign breast tu-
mour with potential for recurrence, malignant transformation and metas-
tasis. The lesion may be morphological heterogeneous, and has potential
Background & Objectives: Triple negative breast cancer (TNBC) to mimic other benign or malignant lesions of the breast, therefore posing
account for 10-20% of all breast subtypes and are associated with a diagnostic challenge.
poor prognosis. There is no approved targeted therapy for these
patients, yet. Programmed death-ligand 1 (PD-L1) expression has
been identified in different cancers achieving good results with im- E-PS-02-049
munotherapy. There is limited data reporting the PD-L1 expression Pathological features of the structure of the endoprosthesis capsule.
in TNBC. The aim of this study is to evaluate the expression of Complications reconstructive breast surgery. Look at the pathologist
PD‑L1 in TNBC patients and to analyse the relationship between N. Volchenko1, I. Shirokih1, M. Yudakova2, V. Surkova1
1
PD‑L1 expression and clinicopathological features of the patients. Moscow Oncology Research Institute - Branch of the National Medical
Methods: Paraffin tissue blocks from 19 TNBC patients were Radiology Research Centre of the Ministry of Health of the Russian
used. PD-L1 immunohistochemistry was performed using mono- Federation, Russia, 2 Multidisciplinary Medical Center of the Bank of
clonal mouse anti-PD-L1, Clone 22C3. Expression of PD-L1 was Russia, Russia
correlated with clinicopathological features. Tumours were defined
as PD-L1 positive if there was membranous expression in ≥ 1% Background & Objectives: The installation of a tissue expander or
of tumour cells. implant immediately after a mastectomy is the most often used
Results Median age at diagnosis was 56 (range 33-74). PD-L1 was method of breast reconstruction. According to American Society
expressed in 7 (36, 8%) of the patients. Six of the patients of Plastic and Reconstructive Surgeons, currently The share of si-
showed low PD-L1 expression (3-20%) and only one patient multaneous breast reconstruction is more than 70%. In Australia it
showed high expression (>50%). The PD-L1 expression showed increased by 9.9% from 1982 to 2000, in Denmark by 14% from
no significant correlation with clinicopathological parameters. 1999 to 2006, in England - by 16.5% from 2006 to 2009 (Platt J.,
Although statistically not significant (p>0,05), PD-L1 was more Baxter N., Zhong T. Breast reconstruction after mastectomy for
often expressed in high grade tumours with larger size, high clin- breast cancer. CMAJ 2011).
ical stage and mutated p53. In our work, we analysed the complications of breast reconstruction:
Conclusion: Expression of PD-L1 was found in more than one third of • Textured endoprostheses
TNBC and correlated with poor prognostic factors. PD‑L1 may be a • Polyurethane endoprostheses
significant marker for predicting prognosis of TNBC patients. These data • Simultaneous reconstruction of the endoprosthesis with additional
need to be confirmed in larger study group. shelter
mesh implant
• Simultaneous reconstruction of the endoprosthesis with additional shel-
E-PS-02-048 ter acellular dermal matrix (ADM) Permacol (porcine)
Adenomyoepithelioma of the breast: a case report with review of Methods: In our study, 79 (50.31%) observations used an implant
literature with polyurethane coating, 78 (49.68%) used an implant with a
L.E.B.F. Luísa Brochado Ferreira1, M. Marques Oliveira1, R. Amorim1, textured coating. Morphological study of the formed endoprosthesis
C. Estima Fleming1, B. Fernandes1, J.R. Brandão1, N. Lamas1, J. Raposo capsule was held in terms of 12 months. after operation.
Alves1, J. Ramon Vizcaino1 (Pic.1,2,3,4)A morphological assessment of the endoprosthesis cap-
1
Centro Hospitalar e Universitario do Porto, Portugal sules with various variants of the endoprosthesis coating (ADM and
mesh implant). Installed 30 endoprostheses with a sheath of ADM
Background & Objectives: Adenomyoepithelioma of the breast is an flap, 2 flaps were examined. Morphological examination of the
uncommon tumour characterised by biphasic proliferation of formed endoprosthesis capsule using ADM, as well as net implant
myoepithelial cells around epithelial-lined spaces. A spectrum of was performed for 14 months. after surgery sharp extrusion of the
histologic patterns may be present, even in different areas of the endoprosthesis (Fig. 5, 6).
same tumour. Because of this heterogeneity, these lesions can be ADM (cell-free dermal matrix)
diagnostically challenging. Although most tumours usually behave Biological implants, or cell-free dermal matrix (ADM) - donor skin flap,
indolently, rare cases have a more aggressive course. For this rea- by special treatment, devoid of its antigenic properties In Russia it is
son, failure to recognize this entity may lead to inappropriate diag- allowed to use ADM Permacol pork.
nosis and management. Hence, accurate diagnosis, and adequate Mesh implants (Fig. 7, 8).
excision followed by close follow-up is mandatory. • Strengthening the lower slope of the reconstructed chest
Methods: A healthy 25-year-old woman, without family history • Creation of additional space for a muscle pocket
of breast cancer, had a palpable right breast mass. The mammo- • Full endoprosthesis shelter
gram showed a heterogeneous nodule, predominantly solid, with • reasonable material cost
cystic areas, and apparently surrounded by a capsule, with Results: 1. Using polyurethane endoprostheses has several advantages.
26.7x14.8 mm in greatest dimensions. A 35×25×15 mm nodule • During healing, dense connective tissue grows into the surface. The
was removed. The nodule was composed by areas of elastic implant is held firmly in place preventing it from dropping • Eliminates
tissues with vaguely multinodular appearance and microcystic/ the displacement outward, as well as the rotation of the anatomical
cystic areas. implant.
 Virchows Arch

• Netting of a fiber capsule similar to a grapevine (with smooth and Background & Objectives: The hydatid disease remains a public health
textured fiber implants arranged in parallel surface). The structure of the problem. However, the cardiac hydatid cyst is rare (0.5-2%).
capsule in the form of a lattice prevents its reduction, thereb reducing the The objective of the work: is to report the rarity of this lesion
occurrence of capsular contracture Methods: We report a case of cardiac hydatid cyst for a man of 50 years,
Microscopic view of the capsule: presented with syncope clinically
• A characteristic microscopic feature is the presence of triangular poly- Results: A chest roentgenogram showed big enlargement of the cardiac
urethane crystals, which are formed over time during resorption polyure- silhouette with deformation of the left arch. The electrocardiogram re-
thane foam endoprosthesis. (Fig. 9) vealed the presence of the complete right bundle branch block. The ultra-
• The fibrous capsule consists of a set of tightly bound tissues that ran- sound cardiac showed a cystic mass fluid in the left ventricle. The
domly intertwined. (pic.10) extracardiac locations were excluded after completion of a comprehen-
• According to our histological data, despite the claimed advantage poly- sive review. The patient died after refusing the surgical treatment. The
urethane coating, in the form of reducing the occurrence of contractures, macroscopic and microscopic study has confirmed the diagnosis of car-
polyurethane triangular structures cause productive inflammatory the re- diac hydatid cyst
action with the presence of giant multi-core cells "type of foreign body", Conclusion: Cardiac localisation of hydatidosis is rare. Polymorphism
which leads to fibrosis and hyalinosis of the capsule tissue, thereby in- Clinical, latency and severity of complications are the essential features.
creasing percentage of occurrence of contracture. (fig.11,12) The treatment is essentially surgical. Medical treatment is limited to dis-
2. Microscopic view of the capsule of a textured endoprosthesis: seminated and non-operable forms. The eradication of this condition in
• The fibrous capsule is constructed of dense connective tissue, the fibers endemic countries requires effective prevention.
of which are located relatively parallel to the surface of the implant, which
reduces its extensibility and increases the percentage of fibrous contrac-
ture (fig. 13,14) E-PS-03-002
• In the fibrous capsule along the inner surface, the pseudo-synovial mem- Morphological features of the peripheral arterial occusive lesions in
brane, as it turned out, it occurs twice as often, of varying degrees of severity, diabetic patients with critical limb ischemia
in contrast to capsules with polyurethane implants. Psevdosinovialny overlay B. Magrupov 1 , S. Temirov 2 , V. Ubaydullaeva 3,1 , T. Kamalov 4 ,
leads to the formation of fluid between the implant and the fibrous capsule B. Tursunov2
1
(seroma). (Fig.15,16) Tashkent Institute of Postgraduate Medical Education, Uzbekistan,
• Inflammatory changes in the fibrous capsule of a textured implant. 2
Central hospital of the ministry of internal affairs, Uzbekistan,
3
Severe lymphoid infiltration with the presence of xanthoma cells, which Republican Research Center of Emergency Medicine, Uzbekistan,
4
also results to the expressed fibrosis and hyalinosis of the tissue of the Republican specialized scientific and practical medical center of endo-
capsules and, as a result, to contracture. (Fig.17,18) crinology, Uzbekistan
3. ADM (cell-free skin matrix)
• Microscopic examination of the endoprosthesis capsule with ADM did Background & Objectives: Critical limb ischemia (CLI) is one of the
not reveal pronounced formation of pseudo-synovial membrane, severe complications of diabetes mellitus (DM). An assessment of the
productive morphological changes of the arteries may help clarify the causes of the
• The inflammatory reaction was found mainly in the thinned skin. flap (in aggressive course of the process in the peripheral arteries in patients with
the reticular and papillary dermis), and in the ADM flap itself is produc- DM.
tive inflammation markedly weak. The synovial membrane in the flap The object of this work was to study the morphological changes in the
examined is not detected (fig. 19, 20). peripheral arteries in the diabetic patients with critical ischemia.
4. Mesh implants: Methods: A morphological analysis of the arteries of the amputated
• Morphological assessment of endoprosthesis capsules with the presence lower limbs was carried out in 14 patients with DM. Specially prepared
of a mesh implant in patients after extrusion of the endoprosthesis Rapid fragments of arteries were studied under a light microscope, and their
germination (large-pore the mesh design fills a three-dimensional colla- morphometric study was also conducted.
gen fiber mesh, which reduces risk of contracture) (Fig. 21,22) Results: In 12 cases of 14 the calcification of the middle layer of anterior
Conclusion: Complications occurring in patients after endoprosthetics de- tibial artery occurred in different severity, in 6 there was a thickening of
pend on the type capsules formed around the implant, which in turn the intimal due to the accumulation of cholesterol and proliferation of
depends on the type of endoprosthesis or additionally covering it. In the smooth muscle cells.
case of polyurethane endoprostheses, complications such as pronounced In the posterior tibial artery, in 11 cases, calcification of the middle layer
productive inflammation ("red syndrome"), appear in the first place, con- in different severity was detected. In 5 cases, an intimal artery thickening
tractures are formed in second place, and the third place is the formation due to the atheromatosis was observed and similar lesions were observed
of seroma. With a textured implant: the formation of contractures, seroma in the peroneal artery.
different severity, inflammatory changes. When using additional ADM Conclusion: Peripheral arterial lesions in patients with DM are not a
closing valves and nets, complications such as contractures and formation purely atherosclerotic process. Considering the presence of middle layer
of seromаs are extremely rare. This technique is used, as a rule, with a calcification, it probably necessary to review the algorithm of pharmaco-
small pinch test, the most frequent A complication in this group of pa- logical therapy in diabetic patients with peripheral arterial occlusive le-
tients is the protrusion of the implant and the addition of pronounced sions, taking into account the disturbance of mineral metabolism.
nonspecific inflammation.

E-PS-03-003
Sunday, 8 September 2019 – Wednesday, 11 September 2019 Giant cell myocarditis associated with immune checkpoint inhibitor
E-PS-03 | Cardiovascular Pathology treatment for metastatic renal cell cancer
A. Bdioui1, K. Amemiya1, P. Bruneval1
1
Hopital Europeen Georges Pompidou, France
E-PS-03-001
Hydatid cyst of the heart, fatal evolution, a case report Background & Objectives: Myocarditis represents a severe complication of
Z. Merad1 cancer immunotherapy. Lymphocytic-type myocarditis has been constantly
1
CHU Sidi Bel Abbes, Algeria reported in this setting. Giant cell myocarditis (GCM) is rare and characterised
Virchows Arch

by a specific histopathology showing giant cells and by inexorable outcome (MI) was carried out. Myocardium for morphological investigation from the
leading to cardiac failure whatever the treatment. We report a case of GCM following area was taken the necrosis zone border zone 2 cm from the
occurring during immune checkpoint inhibitor treatment. necrosis area, opposite to the necrosis of the left ventricle (LV) and the right
Methods: A 53-year old male patient had nephrectomy for renal cell ventricle (RV) walls. Sections were stained with hematoxylin and eosin,
carcinoma in October 2013. From December 2017 to January 2019, pikrofuksinom, Schiff's reagent. Frozen sections were stained with Sudan III.
he received 27 cycles of nivolumab, an anti-PD1 antibody, inducing Results: The zone of necrosis expanded during the first 72 hours. In the
partial metastasis regression without complications. In January 2019 zone bordering the infarction, changes interstitial to the necrosis zone
he was admitted for rapidly progressive cardiac failure (Normal were with observed 8-12 hours delayed. At a distance of 2 cm. there were
coronary angiography; Ejection fraction at 36%, global hypokinetic dystrophic, edema. Perivascular edema, vascular plethora were noted in
left ventricle, and edema at echocardiography and MRI; Troponin T the opposite of the infarction wall of the LV, RV.
at 5,800 □g/L). Conclusion: At recurrent and continuous recurrent MI a pathological
Results: Endomyocardial biopsy showed GCM with extensive myocyte process is more extensive and dystrophic changes along the periphery
necrosis. Viral molecular study was negative. Nivolumab was stopped. are more apparent. An increase of the heart with a predominance of width
Intravenous methylprednisolone pulses were given, followed by tapered over length, an increase in mass by more than 200 grams, and a
oral. Cardiac failure, imaging, and biological parameters improved in a restructuring of the cardiac tracts corresponding should be considered
few weeks allowing discharge from the hospital. Although we cannot as the risk limit for MI development.
definitely rule out coincidence of immunotherapy and occurrence of a
rare type of myocarditis, this case of GCM is very unusual since cardiac
failure, biological and imaging parameters improved under steroid treat- E-PS-03-006
ment and withdrawal of nivolumab. Myocardium: structure-functional relationship
Conclusion: This suggests two hypothesis: 1- GCM could be a second V. Zakharova1,2, E. Trembovetskaya2, A. Balabai3, E. Rudenko2,
type of myocarditis complicating immune checkpoint inhibitors besides T. Savchuk3
1
lymphocytic myocarditis; 2- Autoimmunity could be involved in this Ukrainian Society of Pathologists; International Academy of Pathology,
puzzling type of myocarditis in which so far no viral or immune mecha- Ukraine, 2 Amosov National Institute of Cardiovascular Surgery,
nisms had been documented. Ukraine, 3 Bogomolets National Medical University, Ukraine

Background & Objectives: The Torrent-Guasp theory about unique

E-PS-03-004 myocardial band contradicts the data of histological and functional stud-
Atresia of common pulmonary vein (ACPV) of fetus: an autopsy ies. In 2018 a group of authors from 10 universities published 2 articles in
analysis which they debunked this concept. But the question, how the myocardi-
D. Chen1,2, J. Shang1,3, W. Fang1,3 um provides a complex trajectory of heart movement, needs further study.
1
Department of Pathology, China, 2 Beijing Anzhen Hospital, Capital Objective: to study the role of myocardial architecture in the formation of
Medical University, China, 3 Beijing Anzhen Hospital, Capital Medical a complex trajectory of the heart left ventriculum (LV) movement.
University, China Methods: Macroscopy: 10 boiled prepared pig hearts. Microscopy: serial
histological sections of 16 fetal hearts (abortion at 20-21 weeks of gesta-
Background & Objectives: Objective to investigate pathologic manifes- tion due to medical reasons, not related to the heart pathology): 10 hearts
tations of atresia of common pulmonary vein (ACPV) of fetus by autopsy. were cut across, 3 - in the frontal and 3 - in the sagittal planes.
Methods: Three pathological specimens of atresia of common pulmo- LV mechanics were studied in 35 healthy young volunteers using speckle
nary vein of fetus were studied and who had been found by using tracking echocardiography. The longitudinal displacement, rotation an-
echocardiography. gles and degree of myocardial deformation were evaluated for each of 17
Results: Of the 3 casesone was of complete and two were of incomplete myocardium segments.
atresia of common pulmonary vein. 3 cases were associated with total Results: The apex of the heart rotates counterclockwise by 12,5±1,1°, the
anomalous pulmonary venous drainage (TAPVD). They also had other basal segments – clockwise by 8,3±1,4°. The median LV part doesn’t
complex congenital heart disease and associated with visceral heterotaxy rotate, but moves most of all radially. Basal segments show the maximal
and asplenia. It was different from infant that the fetus was not associated longitudinal displacement, apical – minimal, apex - maximal deforma-
with pulmonary lymphangiectasis. tion. Myocardium is 3D-cardiomyocytic network, the compact layer of
Conclusion: ACPV is an extremely rare congenital heart disease. It is which at the base and apex turn into trabeculae, forming a closed contour.
even more difficult to establish a diagnosis of ACPV if not associated There are bundles in it, the direction of which corresponded to the seg-
with pulmonary lymphangiectasis. mental trajectories of LV movement.
Conclusion: Systolic movement of LV myocardium is provided by a
consolidated contraction of its different segments in the longitudi-
E-PS-03-005 nal, radial and circulatory directions. The motion vector of each
Complex characteristics of various of the heart different forms myo- myocardial segment depends on the orientation of its muscle fibers
cardial infarctions and their contractions sequence. Trabeculae contract first of all and
V. Ubaydullaeva1,2, B. Magrupov2 therefore they are initial fulcrum for cardiomyocytes of the compact
1
Republican Research Center of Emergency Medicine, Uzbekistan, myocardium.
2
Tashkent Institute of Postgraduate Medical Education, Uzbekistan

Background & Objectives: Coronary heart disease remains one of the E-PS-03-007
topical diseases of medicine, connected mortality its prevalence and a HSP70 overexpression in calcified aorta affected by atherosclerosis
stable first place in the structure of the able-bodied population in most A. Romaniuk1, I. Radomychelski2, M. Lyndin3, A. Piddubnyi1, V.
countries of the world. Currently more than 20 risk factors of coronary Sikora3, M. Baumann4, R. Moskalenko1
1
heart disease have been identified. Atherosclerosis is one of the main Sumy State University, Ukraine, 2 Sumy State University, Department
causes of coronary artery disease. of Pathology, Ukraine, 3 Sumy State University, Medical Institute,
Methods: A complex morphological and morphometric study of the heart Department of Pathology, Ukraine, 4 Internistische Fachklinik Dr.
muscle in 247 patients who died from various forms of myocardial infarction Steger Ag, Germany
 Virchows Arch

Background & Objectives: High levels of HSP70 appear to have E-PS-03-0010

atheroprotective effect. It was reposted, that antibodies to HSP70 were Mitral valve caseous calcification with interventricular involvement:
increased in patients with vascular disease. Also HSP70 levels correlate presentation of two cases
with lesion severity. Aim of the investigation was to study the HSP70 S. Papadodima1, J.R. Stone2
1
expression in aortic tissue with calcifications affected by atherosclerosis. Department of Forensic Medicine and Toxicology, National and
Methods: We examined 30 samples of mineralized aorta with calcifica- Kapodistrian University of Athens, Greece, 2 Department of Pathology,
tions (group I) and 10 samples of aorta wall tissue without any signs of Massachusetts General Hospital, Harvard Medical School, Boston, MA
biomineralization (group II). The group II was considered to be a control USA
group. Histological and immunohistochemical methods were used during
the study. Samples were fixed, embedded in paraffin, and analized for Background & Objectives: Caseous calcication of the mitral annulus
HSP70 accumulation using the anti-HSP70 antibody, followed by DAB (CCMA) is a rare variant of mitral annular calcification. Extension of
detection substrate and counterstained with Mayer’s hematoxylin. mitral caseous calcification along the fibrous skeleton of the heart is
Results: HSP70 expression was increased in aortic tissues with extremely rare. We report two cases in which an extensive involvement
calcifications (23.4±1.28 cells per 1 mm2) in comparison to those of the interventricular septum was revealed during the pathological
without them (11.5±1.14, p<0.001, Student test). HSP70 was examination.
mostly localized in cells cytoplasm of macrophages, fibroblasts, Methods: A retrospective analysis of the pathology database of
endothelial cells and smooth muscle cells, also in the tissue Massachusetts General Hospital during the period 2010-2015 was per-
around the calcifications. formed in order to identify cases with CCMA with interventricular sep-
Conclusion: Overexpression of HSP70 was found in several cell tum involvement.
types in aortic mineralized tissue affected by atherosclerosis may Results: Two cases were identified. Case 1. An 83-year-old man
be regarded as its involvement in the formation of such underwent surgical aortic valve replacement. During the surgery, the bi-
biominerals. cuspid aortic valve was found to be heavily calcified. A large amount of
calcium with an area of liquefaction within the interventricular septum
was observed, and a septal myectomy was performed. Pathologic exam-
E-PS-03-009 ination of the interventricular septum revealed patchy calcification with
Angiosarcoma developing in dialysis-related arteriovenous fistulae: areas of caseous calcification. Case 2. A 70 year old female died on the
two cases with review third postoperative day after aortic and mitral valve replacement, left atrial
R. Almeida1,2, H. Moreira1, J. Fraga1, B. Pimentão1, A. Lai1, V. appendage amputation, and decalcification and pericardial patch repair of
Almeida3, C. Faria1, F. Ramalhosa1, R.C. Oliveira1, V. Sousa3, M. the mitral annulus. Gross examination of the heart revealed two well-
Julião1, M.A. Cipriano1 circumscribed, soft, white mass lesions in the interventricular septum
1
Centro Hospitalar e Universitário de Coimbra - Pathology de- focally abutting the mitral valve, which upon histology showed caseous
partment, Portugal, 2 Faculty of Medicine in Coimbra, Portugal, calcification.
3
Institute of Anatomical and Molecular Pathology, Faculty of Conclusion: CCMA is often considered a benign process; it is usually
Medicine of the University of Coimbra, Coimbra, Portugal, asymptomatic and an incidental finding. However, in the case of inter-
Universitário ventricular septum involvement, it may cause several conduction system
disorders. Such interventricular septum involvement may be
Background & Objectives: Arteriovenous fistula (AVF) is the first misinterpreted as a neoplasm on imaging, prompting unnecessary sur-
method considered for vascular access in patients with renal failure, gery.
who require or may require renal dialysis. Recent studies suggest that
AVF should not be ligated post-transplant, except in cases of ischemia,
infections or aneurysms. E-PS-03-011
Angiosarcoma in AVF is a very rare complication in non-functioning Cardiac Fibroma in 4-month-old infant: a case report
fistulae, usually after transplant. Typically, presents as an enlarging pain- D. Anestakis1, I. Leonida1, E. Petrou1, C. Leonida1, E. Chatzifotiou1,
ful lesion of several months duration, and such conditions should raise E. Zagelidou2
1
concern about this entity. Department of Autopsy Histopathology, Lab. of Forensic Medicine and
Methods: A retrospective research at Coimbra Hospital and Universitary Toxicology, Aristotle University of Thessaloniki, Greece, 2 Thessaloniki
Center, over a period of 15y, revealed two cases of angiosarcoma in AVF. Forensic Service, Thessaloniki, Greece
A 82y-old male under hemodialysis, presenting a 4,5cm painful mass in
the right arm, growing over a non-functioning AVF. A 54y-old female Background & Objectives: Cardiac Fibromas are benign primary tu-
with history of renal transplant 15y before, with a pulsatile subcutaneous mours of connective tissue, situated in the heart; especially in the ventri-
lesion in the left arm, 9,5cm, clinically diagnosed as an aneurysm of a cles or in the interventricular septum. The frequency of Cardiac Fibromas
non-functioning AVF. Both patients were submitted to excisional is higher in Paediatric population and ranges from 0.03-0.032% in the
surgery. general population. We report a case about a sudden death of an infant
Results: Histology showed ulcerated neoplasias with deeply infil- with cardiac fibroma.
trating borders, compromising the surgical margins, composed of Methods: The 4-month-old female passed away unexpectedly at home
epithelioid cells, with solid growth and focal vascular-like pattern. without previous hospitalization. There were no symptoms, but the autopsy
Neoplastic cells were vimentin and vascular markers - CD31, examination of the cardiac tissue revealed three white-grey mattered masses
CD34, ERG and Fli-1 - positive, without staining for keratins. composed of fibroblasts located in the ventriclescovering the largest part of
The male patient died 6 weeks after surgery, and the female the cavity.
patient has no known relapse until the moment of submission (1 Results: According to the histological findings, in some parts of the
month after surgery). masses were found homomorphous atractoid cells, disseminated and
Conclusion: Angiosarcoma is a rare mesenquimatous neoplasia, deeply intertwined among collagen fibrils. There were rare inflammatory cell-
invasive with a very aggressive behavior, and a low disease-free survival. clumpingsnear healthy tissue, elements of autolysis, median swelling,
The aim of this work is to warn physicians about the developing of places of median fibrosis around vessels. There were places of fibrotic
angiosarcoma in AVF, particularly in immunosuppressed patients, com- connective tissue inside the myocardium, locally myocardial fibers have
monly after transplant. waveform morphology, layout disorder, while there are inflammatory
Virchows Arch

cells and capillaries with varying degree-thickened walls. There are lo- E-PS-03-014
cally ischemic lesions and presence of neoplasm, which looks like Calcified amorphous tumour of the heart: a case report
fibrosis. C. Gkogkou1, V. Lozos1, E. Koniaris1, E. Nikolopoulos1, K. Tsiardis1, G.
Conclusion: The diagnosis of primary cardiac fibroma is of great impor- Kafiri1
1
tance, because although is benign it might be fatal. The prognosis is poor "Hippokratio" General Hospital of Athens, Greece
if the fibroma is not surgically resectable. There is no prediction depended
on sex or race. Cardiac fibrosis may cause heart failure, cyanosis, arrhyth- Background & Objectives: Calcified amorphous tumour (CAT) is an
mias, syncope, chest pain or sudden death. exceptionally rare endocardial non-neoplastic mass of unknown patho-
genesis that was first described in 1997. Since then less than fifty cases
were reported in the literature.
E-PS-03-012 Here we present a case of CAT because of its rarity and the diagnostic
A rare cardiac benign tumour case report: papillary fibroelastoma challenges it poses predominantly on clinical level.
T. Bolme Savli1, H.E. Pasaoglu2, T.C. Savli3, F. Emre1 Methods: A 75 year-old woman presented with recurrent ischemic
1
Bagcilar Training and Research Hospital, Turkey, 2 Clinical Pathology, strokes. Echocardiographic examination revealed a pedunculated mass
Turkey, 3 Istanbul Training and Research Hospital, Turkey attached to the posterior leaflet of the tricuspid valve. The lesion was
excised and it was submitted for histological examination in three pieces.
Background & Objectives: Papillary fibroelastomas are the third most Grossly the pieces were whitish, solid and hard, with diameter ranging
common cardiac tumours after myxoma and lipoma. Papillary between 0.8-1.3cm.
fibroelastoma is the most common tumours located on cardiac valves. Results: Microscopically the lesion was composed of connective tissue and
Surgical resection should be offered to all patients who have symptoms masses of fibrin with extensive calcification. The connective tissue lacked
and to asymptomatic patients who have pedunculated lesions or tumours hypercellularity and cytologic atypia. A moderate number of foreign body
larger than 1 cm in diameter. multinucleated giant cells were also focally evident. There were no epithelioid
Methods: We report a 75-year-old male patient. A routine echocardio- granulomas, fungal hyphae, parasites or other cellular elements.
gram revealed small pericardial effusion, patent foramen ovale and Based on the above findings, the diagnosis of CAT was established.
1.3x1.2x1 cm sized mobile cardiac mass attached to the aortic valve. Conclusion: Patients with CAT are reported to present with non-specific
Results: The tumour was surgically removed and histopathological ex- symptoms, like dyspnea, arrhythmias or syncope. Clinical awareness of
amination confirmed the diagnosis to be a cardiac papillary this rare entity is required, since its non-neoplastic nature may allow for a
fibroelastoma. conservative management in some, mainly elderly patients. Excised
Conclusion: Although cardiac papillary fibroelastomas are commonly masses should be thoroughly sampled to exclude the possibility of under-
detected incidentally, they can cause embolization and mortality. Since lying granulomatous or neoplastic processes.
our papillary fibroelastoma case causes pericardial effusion and patent
foramen ovale, we found it worth to present.
E-PS-03-015
Brachial artery fusiform aneurysm with intimomedial mucoid de-
E-PS-03-013 generation in a young child - a case report of a rare entity
Leiomyosarcoma of the inferior vena cava and renal vein: a case N.J. Lamas1, M. Oliveira1, L. Ferreira1, C. Fleming1, R. Amorim2, J.R.
report Brandão2, B. Fernandes2, F.E. Costa1, D. Tente1, J.R. Vizcaíno1
A. Ok Atilgan1, E. Yilmaz Akcay1, B. Ozdemir1 1
Anatomical Pathology Service, Department of Pathology, Hospital and
1
Baskent University Faculty of Medicine Pathology Departmant, Turkey University Center of Porto, Porto, Portugal, 2 Centro Hospitalar do Porto,
Portugal
Background & Objectives: Leiomyosarcoma of the inferior vena cava is
a rare mesenchymal tumour originated from smooth muscular fibers of Background & Objectives: Intimomedial mucoid degeneration
the tunica media. They grow slowly and extend to the adjacent tissue. (IMMD) is an extremely rare vascular disorder characterised by mucin
Methods: A 57-year-old-woman had developed an abdominal distention deposition in both the tunica intima and media of arterial walls, with
and pain during the last one year. Radiological imaging revealed a large associated elastic tissue degeneration of both internal and external elastic
mass in the left renal vein extend to inferior vena cava, suprarenal vein, lamina, leading to aneurysm formation.
and ovarian vein. Methods: We report the case of a 4 year-old male child who had two
Results: The patient underwent a left nephrectomy and resection of bilateral brachial artery and right common iliac artery fusiform aneurysms
the vena cava inferior. Macroscopic analysis revealed a 13x7x6 cm detected at 12 months of age through magnetic resonance imaging. The
diameter mass which was grown up an intraluminal extension of in- patient has been under surveillance for nearly 3 years and recently
ferior vena cava, renal vein, suprarenal vein, and ovarian vein. underwent vascular surgery to remove the right brachial artery aneurysm
Extraluminal extension into renal parenchyma, renal sinüs, renal pelvis since the presence of a thrombus was suspected.
was not seen. Cut surface of the tumour was gray-white, firm and Results: A two centimeter tubuliform specimen was received, with fusi-
whorled. In microscopic examination, the tumour showed form morphology, having 3 mm diameter in the surgical ends and 8 mm
hypercellular spindle cell with moderate to severe nuclear atypia, tu- diameter in the middle region. The external surface and the internal lining
mour cell necrosis, increased mitotic activity. Tumour originating from were smooth. The histological analysis showed a large caliber arterial
the wall of the renal vein and inferior vena cava was also observed. wall with marked expansion of the intimal and specially medial layer
Immunohistochemistry showed strong positive staining for caldesmon, secondary to the extensive extracellular deposition of mucin-like material
smooth muscle actin, and negative staining for CD117, DOG-1, (colloidal iron and PAS/Alcian blue positive stainings), with accompany-
S-100, CD34, Fli-1. ing fragmentation of both the internal and external elastic lamina (empha-
Conclusion: Leiomyosarcoma of vascular origin was located in the larger sized using the Van Gieson elastin staining). Furthermore, we could not
vein, especially vena cava. The differential diagnosis includes observe thrombus formation, inflammatory infiltrate, degenerative cysts,
angiosarcoma, leiomyosarcoma, intravenous leiomyomatosis, fibrotic areas or amyloid deposition in the wall (absence of congophilic
sarcomatoid renal cell carcinoma invasion, clinically and pathologically. areas or apple-green pigment under polarized light after Congo Red stain-
Total surgical resection with negative margins of the tumour is the main ing). A diagnosis of intimomedial mucoid degeneration of the brachial
treatment for leiomyosarcoma. artery was made.
 Virchows Arch

Conclusion: This case illustrates the main features of this extremely performed using Ventana Lifesciences Benchmark XT Staining module.
uncommon cause of aneurysm formation. CD38/CD138, IgG and IgG4 were used as antibodies to identify IgG/
IgG4 positive plasma cells.
Results: Increased IgG4 positive cell infiltration was found in four pa-
E-PS-03-016 tients. Two degenerative heart valves with IgG4 positive plasma cells
A rare case of sudden arrhythmic cardiac death fulfilled the generally accepted criteria of >50 IgG4 positive cells/HPF,
R. Henriques de Gouveia1, C. Cordeiro2, F. Corte Real2 one mitral and one aortic valve. However, also two other valves had >20
1
INMLCF & FMUC & CHLO, Portugal, 2 INMLCF & FMUC, Portugal IgG4 positive cells/HPF.
Conclusion: IgG4-related disease may impact heart valves and heart can
Background & Objectives: Among Sudden Cardiac Deaths, be be the first presenting organ of systemic disease.
Arrhythmic ones may be difficult to explain. The authors present a case
with an unexpected cause.
Methods: A 32 year-old male – with medical history of arrhythmia [sus- E-PS-03-019
picion of Wolf-Parkinson-White (WPW) Syndrome] for 12 years –, died Structural changes in the myocardium in cases of sudden cardiac
suddenly during sleep, after a previous physical effort. death in young males
Results: A thorough postmortem examination revealed cardiac pathology A. Sapargaliyeva1, K. Ospanova2, T. Zhakupova2, F. Galitskiy2
– “Persistent Left Superior Vena Cava and Coronary Sinus Orifice 1
Pathology Bureau of the city of Almaty, Kazakhstan, 2 Department of
Atresia”. Forensic Medicine, Astana Medical University, Kazakhstan
Conclusion: This congenital cardiopathy is rare, with 99 known cases
reported, and may be associated to other cardiac malformations and/or Background & Objectives: Mast cells (MC) are found in various tumour
rhythm / conduction disturbances, namely WPW Syndrome type. Being types, but their pro or antitumoural role in prostate carcinoma is still
aware of these associations may facilitate antemortem diagnosis and di- debated. There are divergent opinions regarding MC correlation with
rected therapeutic intervention. prognostic factors. There are also contradictory findings regarding corre-
lations between MC number and Gleason score (GS) in needle biopsy
samples and radical prostatectomy. Our aim was to evaluate the MC
E-PS-03-017 distribution and its correlation with prognostic factors.
Dystrophin Cardiomyopathy Methods: Ninety patients who underwent transurethral resection of the
R. Henriques de Gouveia1, R. Anjos2, J.P. Neves2, S. Ramos2 prostate (TURP) at Colentina Clinical Hospital between 2016-2018 were
1
INMLCF & FMUC & CHLO, Portugal, 2 CHLO, Portugal selected for this study. We generated multi-tissue blocks and stained mast
cells immunohistochemically with tryptase. We evaluated the mast cells
Background & Objectives: Cardiomyopathy is a phenotypic manifesta- infiltrate density in peritumoural and intratumoural areas and correlate the
tion of Dystrophinopathies. The authors present such a case. data with GS.
Methods: A 23 year-old male, with family and personal medical history Results: The ages of patients ranged from 53 to 91 (median 71 years).
of Dystrophinopathy, was submitted to heart transplantation due to car- There was no correlation between age and MC count. We found that
diac failure. The native heart specimen was sent to anatomo-pathological higher MC counts correlate with lower prognostic group (p<0.05), similar
examination. to studies conducted on prostatectomy and in contrast with needle biopsy
Results: Macroscopic and microscopic evaluation (complemented with samples. We found a difference in MC counts from intratumoural areas
histochemistry and immunohistochemistry) revealed a “Dilated comparative to peritumoural areas. GS was negatively correlated with
Cardiomyopathy Dystrophin-Deficient”. intratumoural MC number (p<0.001).
Conclusion: The present case intends to draw attention to Dystrophin Conclusion: Higher MC number correlates with better prognosis sug-
Cardiomyopathy, since with increased survival of dystrophinopathies’ gesting that MC can be a reliable prognostic marker in prostate cancer.
affected persons due to therapy improvements and classic complications Differences in MC number in needle biopsy versus prostatectomy and
control, cardiac involvement (25% to 90%) has become an important TURP may be due to smaller stromal areas identified in the biopsies. MC
cause of morbidity and mortality. may play a role in the relationship between stromal microenvironment
and tumour cells and can be a potential target of effective antitumour
strategies.
E-PS-03-018
IgG4 related disease in heart valves
T. Paavonen1, E. Niinimäki2, A. Mennander3, I. Kholová4 E-PS-03-020
1
Department of Pathology, Fimlab Laboratories and Department of Hydrophilic polymer cardiac emboli: postmortem case report
Medicine and Life Sciences, University of Tampere, Finland, F. Filipello1, N. Ahmed1, C. Doglioni2,1, F. Sanvito2
2 1
Department of Anesthesiology, Southern Carelian Central Hospital, Vita-Salute San Raffaele University, Milan, Italy, 2 Pathology Unit,
Lappeenranta, Finland, 3 Department of Cardiothoracic Surgery, Heart Division of Experimental Oncology, IRCCS San Raffaele Scientific
Hospital, Tampere University Hospital, Tampere, Finland, 4 Department Institute, Milan, Italy
of Pathology, Fimlab Laboratories and University of Tampere, Finland
Background & Objectives: Hydrophilic polymer emboli (HPE) are a
Background & Objectives: Immunoglobulin G4 (IgG4) related disease possible complication of intravascular procedures and have been reported
is a systemic disease involving various organs as well as vascular struc- in heart and other organs.
tures like aorta. There is rather limited data on IgG4-related disease in We describe two postmortem examinations of sudden cardiac arrest with
other vascular tissues for example heart valves. histological features of HPE in myocardium.
Methods: Sixty surgically resected heart valves were included (48 aortic Methods: The first case (A) was a 44 year-old man, arriving in
and 12 mitral valves). There were 44 males and 16 females with a mean Emergency Department (ED) in cardiac arrest. He received cardiac cath-
age of 60 years. There were 24 valves with endocarditis (19 acute endo- eterization with coronary stenting due to thrombosis of the anterior inter-
carditis, 3 chronic endocarditis, and 2 healed endocarditis). Degeneration ventricular artery (IVA). No evidence of cardiac function recovery was
was the main diagnosis in 36 cases, of which 17 had significant inflam- recorded and, 24 hours later, expired. The second case (B), a 52 year-old
mation without full criteria of endocarditis. Immunohistochemistry was man pacemaker assisted, arrived in ED with cardiac arrest in suspected
Virchows Arch

myocardial infarction and died before any treatment was given or any lymphoma is predominately of B cell lineage with diffuse large B-cell
clinical history was taken. lymphoma being the most common histological type. Cardiac lymphoma
Results: Postmortem examination of case A: the metal stents in the IVA often involves the right heart, especially the right atrium. Epicardial and
were in place and patent. Acute infarction with prior ischemic events of pericardial infiltration with pericardial effusion is typical. Clinically, and
the left ventricle were detected. Basophilic, amorphous material was pres- contrarily to primary cardiac lymphoma, generalized lymphoma involv-
ent in the small vessels of the myocardium. ing the heart is rarely initially revealed by cardiac manifestations. When
Case B revealed two bare metal stents in the IVA occluded by thrombi present, cardiac symptoms are most commonly associated with pericar-
and microscopic evaluation displayed amphophilic to basophilic, amor- dial effusion and congestive heart failure. Arrhythmias and sudden heart
phous material in the intramyocardial vessels associated with inflamma- death are not uncommon.
tory cell infiltrate with foreign-type giant cells in the left ventricle. We report a new case of cardiac lymphoma in a young female adult with
Conclusion: Although HPE may not have been the ultimate cause of an unusual clinical presentation.
death, it is possible that they contributed to the clinical outcome of pa- Methods: In a case of secondary cardiac lymphoma, the clinical and
tients. At present, attention has been focused on this issue, nevertheless pathological parameters are studied and discussed.
the role and the complications of myocardial HPE are poorly understood Results: We report a case of a 32 year-old female reporting dyspnea and
by clinicians and pathologists. multiple episodes of syncope. Echocardiography, CT scan and MRI reveal an
ill-defined, myocardial infiltrating mass localized in the right atrium and
associated with moderate pericardial effusion, bilateral ovarian involvement.
E-PS-03-021 However, no mediastinal adenopathy was seen. A suspected meningeal in-
The new concept of the interstitium explains the microscopic features volvement was confirmed on cerebrospinal fluid pathological analysis.
and pathogenesis of a case of hypertensive pneumopericardium Grossly, the surgically removed cardiac lesion presented as a 5 cm large
K. Metze1, N.B. de Almeida1, F.A. Borges da Silva1 whitish firm multinodular mass. Histological examination revealed an
1
State University of Campinas, Brazil undifferenciated malignant proliferation composed of diffuse sheets of large
and atypical immunoblast-like cells. Multiples areas of tumour necrosis were
Background & Objectives: Recently a new concept of the interstitial found. The proliferation’s immunophenotype was characterised by CD20
space has been created (Scientific Reports, 2018,8:4947). In this autopsy positivity and the negativity of CK, CD3, CD30, CD117 (c-kit) and CD99.
report of a patient with hypertensive pneumopericardium we want to Thus, the diagnosis of cardiac diffuse large B-cell lymphoma was established.
show how this new theory helps to explain the morphologic findings Treatment included systemic and intrathecal rituximab-based chemotherapy
and the pathogenesis of this disease. followed by autologous peripheral blood hematopoietic stem cell transplan-
Methods: A girl of two months was hospitalized due to respiratory distress tation. The patient had however a lethal outcome.
provoked by viral bronchiolitis. During mechanical ventilation she suffered Conclusion: Although our patient was affected by generalized malignant
a sudden decrease in oxygen saturation followed by cardiac arrest. lymphoma involving her heart, she had only cardiac symptoms at initial
Resuscitation attempts were unsuccessful. An autopsy was performed. presentation which is unusual with this type of malignancies. Like the
Results: Macroscopic inspection revealed mediastinal emphysema. majority of cardiac lymphomas, diffuse large B cell lymphoma was the
When opening the pericardium under water hypertensive histological type encountered in our case. Even though being sensitive to
pneumopericardium was seen. chemotherapy, cardiac lymphoma keeps carrying a poor prognosis as
Microscopic examination showed many confluent “empty” spaces in the attested by this observation.
peritracheal and mediastinal connective tissue, as well as in thymus and
lymph nodes, creating smaller or larger tissue islands. We interpreted
these spaces as channels of air propagation.The pericardium revealed also E-PS-03-023
these channels connected to those of the other mediastinal organs and On application of cardiac fish preparations in education and re-
terminating in myriads of microscopic submesothelial bubbles. search of pathology
Conclusion: The new concept of the interstitium postulates a widespread E. Neu1, B. Rattel2, M. Michailov1, T. Plattner1, P. Birkenbihl1, T. Senn1,
fluid-filled pre-lymphatic space within and between different tissues. We V. Foltin3, G. Weber4, D.G. Weiss5
1
believe, that after a microscopy tracheal rupture mechanic ventilation Inst. Umweltmedizin c/o ICSD/IAS e.V. Muenchen, Germany, 2 Amgen
injected pulsating air into the interstitium, until reaching the pericardial Res. Munich (Exec. Dir.) & IUM c/o ICSD/IAS e.V., Germany, 3 St.
space. There the alignment of the interstitial space (parallel or oblique to Elisabeth Univ., Bratislava, Slovakia, 4 Univ. Lxbg. and Vienna, Fac.
the mesothelial surface) created and air-trapping mechanism, which Psychology (Dean), Austria, 5 Univ. Rostock, Inst. Physiology
caused the lethal hypertensive pneumopericardium. (Dir.a.D.), Germany

Supported by CNPq Background & Objectives: In medical education&research are till today
usual cardio-vascular preparations of frog, rat, rabbit,etc. An es-
sential part of experiments with isolated angio-cardiac preparations
E-PS-03-022 could be replaced by fish organs. About pharmaco-physiological reac-
Secondary cardiac lymphoma with unusual clinical presentation: a tions of fish heart of salmo gairdneri is reported [1,3]. Now is given
case report information about effects of xenobiotics leading to pathophysiological
A. Saidi1, I. Msakni1, R. Hedhli2, N. Mansouri1, F. Gargouri1, A. Bouziani1, reactions.
B. Laabidi1 Methods: Isolated fish heart (atrium, ventriculus cordis) from rainbow-
1
Pathology Department; Military Hospital for Instruction of Tunis, trout: Registration of spontaneous contractions (isotonic rec.) in Krebs-
Tunisia, 2Tunis El Manar University, Medicine School of Tunis Henseleit-solution (n=120, p<0.05<0.01) [1].
Military Hospital of Tunis, Department of Pathology, Tunisia Results: Atrium & ventriculus cordis generate spontaneous
regular&uniform contractions (6-24°C). Ethanol (0.01-0.5%) and butanol
Background & Objectives: Cardiac lymphoma is an extra nodal lym- (0.001-0.01%) transform regular contractions of atrium into burst-like
phoma usually secondary to a disseminated disease. Primary cardiac lym- ones. HgCl2 10nmol/l also induce similar transformation with very long
phoma is a very rare malignancy defined as involving only the heart and/ burst-duration. Inotropic effect is not changed. Cypermethrin 10μmol/l
or pericardium or with limited extra cardiac involvement. It affects more has similar effect, but with strong negative inotropic effect. Their differ-
frequently adult men and carries an overall poor prognosis. Cardiac ences in effects in fish ventriculus cordis are observed.
 Virchows Arch

Conclusion: Fish cardiac preparations could be used as sensitive indica- Background & Objectives: Fine needle aspiration cytology of thyroid
tor for xenobiotics in water. Further, fish preparations could reduce enor- gland (FNAC) is a generally accepted, minimally invasive, fast and eco-
mous application of animal organs in academic education&research nomical procedure that determines algorithm for treating nodular thyroid
(universities) as well as in pharmacological industry, leading to large lesions. FNAC routine application has reduced the number of
animal protection. thyroidectomies.
Ref.: We analysed performed thyroidectomies and presence and reliability of
1. Neu, Weiss, Michailov et-al.: IUPHAR-1994-Montreal. preoperative FNAC of nodular thyroid lesions.
Can.J.Phys.&Pham., p.164 (1994) Methods: Retrospectively, pathohistological reports (PH) of patients who
2. Neu, Michailov, Bauer et-al.: IUPS-2009-Kyoto. J.Physiol.Sci. Proc underwent partial/total thyroidectomy in the period 2014-2018 were analysed
IUPS Vol.XXII Springer, p.249 (2009) at the Center for Pathology and Histology of the Clinical Center of Vojvodina.
3. Michailov, Neu, Welscher et-al.: IUPS-2017-Rio de Janeiro, Abstract- Patients with preoperative FNAC were marked and analysed.
Book ID977, Proc.XXIV (2017) Results: In five-year-period, 395 thyroidectomies were performed with
DEDICATION for moral-scientific support 2018-1980/Nobel Laureates: female predominance. The average age was 51. The preoperative FNAC
Australia: Sir J.Eccles, Austria: K.Lorenz, Belgium: I.Prigogine, Canada: was found only in 10.9% of the total number. The positive correlation of
G.Herzberg, J.Polanyi, France: J.Dausset, J.-M.Lehn, Germany: FNAC and PH findings was registered in 84.7% of cases with 73.3%
M.Eigen, K.v.Klitzing, H.Michel, E.Neher, GB: Sir A.Hewish, sensitivity. False positivity was present in 26.6% cases, while false neg-
B.Josephson, Lord A.Todd, India/USA: S.Chandrasekhar, ativity in 42.9%. Positive predictive value was registered in 47.8% and
H.B.Khorana, Japan: K.Fukui, Sweden: S.Bergström, B.Samuelson, negative predictive value in 80% cases. AUS category consisted of 20%
USA: P.Anderson, J.Deisenhofer, D.Hubel, L.Pauling, E.Wiesel malignant and 80% benign PH diagnoses.
Conclusion: FNAC of thyroid gland is accurate method which remark-
ably reflects the biological nature of thyroid lesion providing faster, less
Sunday, 8 September 2019 – Wednesday, 11 September 2019 expensive and more reliable diagnosis of thyroid solitary nodes than any
E-PS-04 | Cytopathology other clinical and laboratory tests. The main problems are caused by
inadequate or borderline aspirates of the thyroid node and taking inade-
quate material without the diagnostic cells in the smear.
E-PS-04-001
Antigen stability of cells stored in in-house liquid-based cell medium
U. Klopcic1, A. Kuhar1, N. Nolde1, V. Kloboves-Prevodnik1
1 E-PS-04-003
Institute of Oncology Ljubljana, Slovenia
Pleomorphic carcinoma of the lung: diagnostic utility of fine needle
aspiration
Background & Objectives: Our study was designed to test how long the
K. Kuan1, S. El Hussein1, S. Khader1
antigen properties of cells stored in our in-house liquid based cell medium 1
Montefiore Medical Center/Albert Einstein College of Medicine,
are retained and immunocytochemical (ICC) reactions for estrogen recep-
Department of Pathology, USA
tor (ER), MOC-31, CK AE1/AE3, CD45, Calretinin and Melanoma triple
cocktail can safely be performed.
Background & Objectives: Pleomorphic carcinoma of the lung is an
Methods: Each of the ICC markers was tested on ten different cell samples. exceedingly rare tumour that has only been recognized recently and clas-
For each sample cytospins were prepared and fixed in methanol on the day of sified by the World Health Organization in 2015. As its incidence only
the sampling and then subsequently on the second, fourth, fifth and eight day makes up to 0.4% of all lung malignancy, few studies are done on this
of the sampling. Percentage of positive cells, intensity of ICC staining, back- entity. Here we present a case of metastatic pleomorphic carcinoma diag-
ground, counterstaining and morphology were evaluated on 300 tested slides. nosed with fine needle aspiration (FNA). This case report aims to high-
Each tested slide had its respective negative control. Assessment criteria were light the cytologic features of this tumour and correlate them to its histo-
adopted from UK NEQAS ICC scheme. logical counterparts.
Results: Percentage of positive cells and intensity of ICC staining of CK Methods: A 70-year-old, female who is chronic smoker was found to
AE1/AE3, MOC-31, CD 45, ER and Melanoma triple cocktail were have a mass in the right lung and subsequently underwent right pneumo-
similar even after eight days storage of cell sample in in-house liquid nectomy. Histological examination revealed the tumour to be pleomor-
based cell medium, while the percentage of positive cells in Calretinin phic carcinoma of the lung. Despite being on intense adjuvant chemo-
ICC stained slides dropped significantly after the fourth day. Background, therapy, the disease still progressed. An ultrasound-guided FNA was per-
morphology and counterstaining changes did not affect the percentage of formed later on an enlarged peri-pancreatic lymph node. Diagnosis of the
positive cells and intensity of ICC staining. FNA was made based on the cytomorphology of specimen and ancillary
Conclusion: Cells stored in in-house liquid-based cell medium retained studies including immunohistochemical (IHC) stains and genetic testing
unchanged antigen immunoreactivity for at least four days in our series. were performed.
The time period in which antigen immunoreactivity of cells stored in in- Results: The tumour cells from both the surgical specimen and the FNA
house liquid medium is still retained should be tested for each ICC marker biopsy showed poorly differentiated glandular structures admixed with
individually. undifferentiated epithelioid cells and giant cells. Although the IHC stains
of surgical specimen were positive for TTF-1, Napsin 1, they were not
expressed in the cell block from FNA. Follow-up molecular study, how-
E-PS-04-002 ever, identified the same EGFR mutation at exon 18 (719 G>X) in both
Reliability of fine needle aspiration of thyroid gland sample. This finding greatly supported the diagnosis of metastatic pleo-
A. Ilic1,2, D. Miljkovic1, M. Panjkovic1, J. Ilic Sabo1,2, Z. Vrekic2, M. morphic carcinoma from the known lung primary.
Miladinovic3,4 and T. Lakic1,2 Conclusion: Pre-operative diagnosis of pleomorphic carcinoma of
1
University of Novi Sad, Faculty of Medicine, Serbia, 2 Clinical the lung can be very challenging, in part because of the scarcity
Center of Vojvodina, Novi Sad, Center for Pathology and of cases describing this entity on surgical biopsies or FNA biopsies.
Histology, Serbia, This case beautifully highlights and correlates the cytologic and
3
University of Montenegro, Faculty of Medicine, Montenegro, 4 histologic features of pleomorphic carcinoma of lung, emphasizing
Clinical Center of Montenegro, Podgorica, Center for Pathology, the crucial role that FNA plays in providing adequate assessment of
Montenegro unusual cases.
Virchows Arch

E-PS-04-004 histopathology after later core needle biopsy. The pathological examina-
Pulmonary adenocarcinoma with enteric differentiation: a diagnostic tion revealed positivity of both tumours using immunostaining: estrogen
pitfall and progesterone receptors, HER2 and E-cadherine.
K. Kuan1, S. El Hussein2, S. Khader2 Conclusion: We report a rare case of contralateral infiltrating ductal car-
1
Montefiore Medical Center/Albert Einstein College of Medicine, cinoma and mucinous carcinoma diagnosed during the initial presenta-
Department of Pathology, USA, 2 Montefiore Medical Center/Albert tion. This highlights importance of fast and minimal invasive cytologic
Einstein College of Medicine, USA examination in detecting potential pitfall in the diagnostic imaging of the
setting of benign-appearing lesions, especially if there is more lesion. It is
Background & Objectives: Lung cancer is the second most common also possible to differentiate histological types of breast carcinoma and
malignancies in the United States. Much work has been put into classi- instruct that these are different primary ones and not metastatic tumours,
fying and characterizing various types of pulmonary malignancies in as well as to confirm these are synchronous tumours. Meticulous histol-
order to optimise treatment plans. Recently, an uncommon variant of lung ogy diagnosis and appropriate management helped to improve the lon-
cancer that resembles colorectal adenocarcinoma is recognized by differ- gevity with an improved quality of life.
ent scholar bodies and the term pulmonary adenocarcinoma with enteric
differentiation (PAED) is coined to this subtype. Here, we present a case
report of PAED that is diagnosed with fine needle aspiration (FNA). E-PS-04-007
Methods: An 85-year-old male with a remote history of prostate adeno- Neoplastic pleural effusion involvement and ggynaecological tu-
carcinoma presented to the emergency department complaining of persis- mour: a rare association
tent abdominal pain. Except for an increase in CEA level, laboratory J. Fraga1, F. Ramalhosa1, C. Faria1, B. Pimentão1, A. Lai1, H. Moreira1,
work-up was otherwise unremarkable. Imaging studies revealed multiple V. Almeida1, R. Almeida1, C. Oliveira1, G. Fernandes1
1
pulmonary nodules, with a predominant mass measuring 5.7 cm. Hence, Centro Hospitalar e Universitário de Coimbra, Portugal
biopsies were performed on the largest mass via CT-guided fine needle
aspiration (FNA) and core needle biopsy. Diagnosis was made based on Background & Objectives: The thorax is a frequent site of metastasis
the cytomorphology and immunochemical (IHC) stains were used for from non-pulmonary cancers. Intrathoracic metastatic disease may man-
confirmation. ifest in many forms. There are a limited number of studies giving the
Results: The cells collected from FNA demonstrated gland-forming, co- incidence of pleural metastasis from female genital tract tumours.
lumnar carcinoma cells, with vacuolated cytoplasm and basally oriented Methods: We present a 62 year old woman with progressive worsening
nuclei. The core needle biopsy finding was in congruence with the FNA of general condition, with clinical information of two pulmonary nodules
biopsy, revealing an adenocarcinoma arising from the alveolar lining, in right lung and pleural effusion. Posterior dissection of previous clinical
with bland enteric-like columnar cells. Furthermore, IHC stains of the history revealed a diagnostic of an endometrial adenocarcinoma four
cell block were positive stain for CK7, TTF-1, and CEA-M. As such, years ago.
these findings along with the IHC results were consistent with a primary Results: Inclusion in paraffin of the sediment obtained after centrifuga-
lung adenocarcinoma with enteric differentiation. tion of pleural effusion, resulted fibrin imprisoning irregular glandular
Conclusion: Pulmonary adenocarcinoma with intestinal features is a structures constituted by cells with accentuated nuclear pleomorphism,
newly recognized, uncommon entity that we have limited understanding hyperchromasia and high nuclear/cytoplasm ratio. This cells had cyto-
of its pathogenesis. As this case illustrates, the cytomorphology of PAED plasmic membrane immunoexpression for BerEp4, cytoplasmic positiv-
can be very misleading. The use of IHC stains and the clinical correlation ity for Ck7 and vimentin and nuclear positivity for p53, Pax8 and p16 and
is crucial for making this diagnosis in order to avoid diagnosing this as negativity for GATA3 and TTF1.
metastatic disease of colorectal adenocarcinoma. Conclusion: Due to the ambiguous clinical history, our study was con-
ditioned by the multiple possible origins of the neoplastic cells.
Cytological diagnosis was a pleural involvement by of high grade serous
E-PS-04-006 adenocarcinoma of endometrium. Only 2%–4% of tumours of the female
Primary synchronous bilateral breast carcinomas: correlation be- genital are disseminated at the time of presentation, usually, spreading to
tween cytopathologic and radiologic findings pelvic and para-aortic nodes by the lymphatic system or to distant organs
V. Skuletic1, S. Cerovic2, B. Kovacevic2, D. Mikic1, J. Dzambas1, N. by the hematogeneous system. Thoracic metastases from ggynaecologic
Stepic2, M. Elez2, I. Zenilo2, M. Zaric2 malignancies exhibit various imaging patterns. Metastases from endome-
1
Military Medical Academy, Serbia, 2 Military Medical Academy, trial cancer typically manifest as pulmonary nodules and lymphadenopa-
Belgrade, Serbia thy, whereas ovarian cancer often manifests with small pleural effusions
and subtle pleural nodules.
Background & Objectives: Synchronous bilateral breast cancers (SBC)
are rare entities with incidence of 2-5% of all breast malignancies.
Physicians consider a synchronous contralateral cancer which are diag- E-PS-04-008
nosed within 1 month to 1 year of each other. The second tumour is Significance of nuclear morphometry in fine needle aspiration from
generally considered to be an independent lesion (rather than metastasis) benign tumours and invasive carcinomas of breast
if it contains an in situ component, has a different histology from the first H. Sheikh Alard1
1
tumour, or possesses a different degree of differentiation from the first Damascus University, France
tumour.
Methods: A 46 year old female presented with 8 cm firm mass in upper Background & Objectives: Fine-needle aspiration of breast masses is a
outer and inner quadrant of right breast and 1,5 cm tumour felt in the left safe and cost-effective technique for the diagnosis but this diagnosis is
breast, on the border of upper outer and lower outer quadrant. still aubjective. The nuclear morphometry can reduce this subjectivity
Mammography and corresponding ultrasound of the right breast revealed when it is applied on the aspiration of breast masses.
malignant-appearing with a contralateral benign-appearing suspect on Objectives: measuring the nuclear area and perimeter then
fibroadenoma. - comparing these values between the benign masses and invasive
Results: Ultrasound-guided core needle biopsy with imprint cytology of carcinomas.
the right breast showed ductal carcinoma while FNA of the left breast - studying if there is a relation between those values and a) carcinoma's
lump suggested mucinous carcinoma which was confirmed on grade evaluated on aspirations, b) carcinoma's grade evaluated on
 Virchows Arch

histolofical sections, c)status of lymph nodes in the same side, d)size of -The variations in the values of NA and N are more important in the group
mass, and e)degree of cohesion of carcinoma's cells. of invasive carcinomas grade 3 than in the group of invasive carcinomas
- evaluating the average of variations in the values of nuclear area and grade 2.
perimeter between the group of benign masses and invasive carcinomas. -The NA in the group of invasive carcinomas with nuclear grade 3 eval-
Methods: 101 masses sent to the department of surgical pathology in the uated on FNA are bigger than those of invasive carcinomas with nuclear
two hospitals of damasuc university for frozen sections, between 2015- grade 2and 1.
2017. -The difference between NA and NP of cohesive cellls in clusters and
The aspiration had been performed on these masses (G210). The smears those of isolated cells has a prognostic value for the metastases in lymph
have been fixed with ethanol 90% and stained with hematoxyline eosin. nodes but the nuclear morphometry itself doesn't have a prognostic sig-
The slids of aspirations and the slids of histological sections have been nificance for the metastases in lymph nodes.
scanned by NIKON (HDCE-10C). The nuclear area and nuclear perime- -No relation between nuclear morphometry (NA and NP) and the size of
ter have been measured by an open source image processing program invasive carcinomas.
(Image J).
The nuclear grade of invasive carcinoma has been evaluated by using the
Robinson's system. E-PS-04-009
The histological grade of invasive carcinomas has been evaluated by Cytological and histological aspects of tall cell and hobnail variant of
using the Nottingham modification of Bloom-Richardson system. papillary thyroid carcinoma: 3 cases
Abbraviations: Nuclear area NA, Nuclear perimeter NP. U. Aykutlu1, C. Uzun1, M. Ozsen1, Y. Cakir1
Results: - There is a statistical significance for the difference between: 1
Erzurum Regional Training and Research Hospital, Turkey
a) NA, NP and the average of variations of these values of isolated cells in
benign masses and those in invasive carcinomas. Background & Objectives: Papillary thyroid carcinoma (PTC) is the
b) NA and NP of cohesive cells in clusters and this of isolated cells in the most common tumour among the thyroid malignancies. This presentation
group of invasive carcinomas. aim to present the clinicopathological features of tall cell and hobnail
c) NA of cohesive cells in clusters and the nuclear area of isolated cells in variant of PTC cases.
the group of invasive carcinomas.
Methods: We report three cases diagnosis with tall cell and hobnail
d) NA and NP of the group of invasive carcinoma with nuclear grade 1
variant of PTC by fine needle aspiration and total thyroidectomy
and those with nuclear grade 2 and 3.
procedure.
e) NA and NP of cohesive cells and this of isolated cells in the group of
invasive carcinoma with N+. Results: One of the 2 cases diagnosed with Tall cell variant of PTC is 65
f) NA and NP of cohesive cells and isolated cells and also mean nuclear years old male. The other case is 48 years old, female. Microscopic
morphometry in the group of invasive carcinoma with histological grade examination of fine needle aspiration (FNA) material show numerous
2 and those in the group of invasive carcinoma with histological grade 3 intranuclear inclusions and atypical thyrocytes with long cytoplasm
(the specimen of invasive carcinoma grade 1 is not sufficient for statistical aligned near basal nucleus alignment. Histopathological evaluation re-
study) vealed a tumoural lesion with the features of distinct restrictive papillary
- No statistical significance for the difference between: thyroid carcinoma, which consisted of long cylindrical cells, of which
a) NA and NP of cohesive cells and mean nuclear morphometry in benign heights are at least 2-3 times their width.
masses and those in invasive carcinomas. The case, which is diagnosed as Hobnail variant of PTC, is 51 years old
b)the average of variations in the values of NA of cohesive cells in benign male. Microscopic examination of FNA material showed atypical
masses and those in carcinomas. thyrocytes with papillary thyroid carcinoma characteristics, as well as
c) NA and NP of cohesive cells in clusters and this of isolated cells in the dyscohesive cells with loss of polarity and isolated cells with eccentric
group of benign tumours. nucleus and teardrop-shaped cytoplasm. Histopathological evaluation re-
d) NA and NP in the 4 groups of lymph nodes status of invasive vealed a tumoural lesion composed of complex papillary and
carcinomas micropapillary structures with nuclear cells that have features of papillary
e) NA and NP of the group of invasive carcinoma with N+ and this of N-. thyroid carcinoma. Apical localised nuclei of the tumour cells show typ-
f) NA and NP of cohesive cells and this of isolated cells in the group of ical hobnail pattern.
invasive carcinoma with N-. Conclusion: Most of the PTC variants have good prognosis, however tall
g) NA and NP of the 4 groups of invasive carcinoma's size. cell variant, hobnail variant, columnar cell variant are associated with
h) NA and NP in the three degrees of cohesiveness of carcinomatous poor prognosis. It is important to distinguish these variants from the
cells. classical variant for better patient management.
- NA: benign tumours (64.14 +/-18.68)um2, invasive carcinomas
(109.69+/-39.53)um2.
- NP: benign tumours (28.41+/-6.67)um2, invasive carcinomas (43.87 +/- E-PS-04-010
3.89)um. Parotid gland metastasis from endometrial cancer: first reported
Conclusion: -The NA and NP play an important role in distinguishing the case with cytologic description
benign tumours from invasive carcinomas, specially isolated cells (values S. Lajara1, R. Balakrishnan1, C. Castrodad1, A. Colanta1, S. Khader1
1
of isolated cells in invasive carcinomas are bigger than those of isolated Montefiore Medical Center/Albert Einstein College of Medicine, USA
cells in benign tumours).
-The difference between the NA and NP of cohesive cells in clusters and Background & Objectives: Endometrial adenocarcinomas are the most
those of isolated cells is bigger in the group of invasive carcinomas than common ggynaecologic malignancies in the USA. Type 1 is associated
in the group of benign tumours with statistical significance. with low stage at diagnosis and better prognosis, while type 2 is associ-
-the average of variations in NA and in NP in the group of invasive ated with increased intraperitoneal and metastatic spread. Typical meta-
carcinomas are more important than the average of variations of these static sites include regional lymph nodes and lungs; uncommon sites are
values in the group of benign tumours. the liver, adrenals, soft tissue, bone and brain.
-The values of NA, NP and mean values in the group of invasive carci- Our aim is to describe an unusually widely metastatic well-differentiated
noma with histological grade 3 are bigger than those in the goup with endometrial adenocarcinoma and the cytologic findings of a fine needle
histological grade 2. aspiration (FNA) of the parotid gland, a rare site of metastasis.
Virchows Arch

Methods: We report a case of a 65-year-old female with a past medical Methods: A 69-year-old female patient was admitted to our hospital with
history of well-differentiated, FIGO stage IB endometrioid endometrial a progressively enlarging swelling of the left supraclavicular region for
adenocarcinoma, presenting with a necrotic intraparotid lymph node. approximately 4 weeks. Ultrasonography of the neck revealed multiple
Two years prior to presentation, she was diagnosed with multiple brain nodules, with rounded and heterogenic echo parenchyma which sug-
lesions, managed as cancer of unknown primary site. Her endometrial gested metastasis. An ultrasound-guided fine needle aspiration biopsy
cancer was considered as an unlikely primary because the brain is an was performed from the largest mass of the left supraclavicular region.
uncommon metastatic site. However, pathology revealed metastatic en- Cytology revealed carcinoma metastasis. Immunohistochemical exami-
dometrial adenocarcinoma. A gingival nodule, identified during dental nation showed the tumour cells at the cell block to be positive for CK20
extraction, also revealed metastatic adenocarcinoma. and CDx2 and negative for CK7 and p40 expression. The positron emis-
Results: FNA of her left parotid gland revealed scattered clusters of large sion tomography (PET) of the patient, which was investigated for etiolo-
pleomorphic cells with prominent nucleoli and moderate to abundant gy and origin, was observed hypermetabolic area that about 6x3 cm at the
pale, sometime clear cytoplasm compatible with metastatic endometrial transverse colon. Upon this the patient was performed right
adenocarcinoma. hemicolectomy and excisional biopsy of left supraclavicular lymph node.
Conclusion: An aggressive clinical course with extensive distant metas- Results: Macroscopic examination of the right hemicolectomy showed a
tasis is peculiar for low-stage, well-differentiated endometrial adenocar- infiltrating mass measuring 4x4 cm on the transvers colon and the tumour
cinomas. Brain involvement is extremely uncommon, and is usually seen extended into the pericolic fat. Histologically the appearance was moder-
in high grade and high stage tumours. Gingival metastasis is also vanish- ately differentiated colonic adenocarcinoma. Histopathologic examina-
ingly rare. To our knowledge, there is no reported case of endometrial tion of the left supraclavicular lymph node again confirmed as metastasis
carcinoma involving the parotid gland in literature. from colonic adenocarcinoma.
Conclusion: Supraclavicular lymph node metastases are common occur-
rence in breast cancer, lung cancer, gastro-oesophageal cancer and lym-
E-PS-04-012 phoma. Colonic cancer represents an unusual primary for supraclavicular
Cytologic features of gastric type mucinous carcinoma of the uterine lymph node metastases.
cervix
K. Suh1, K. Kim1
1
Chungnam National University Hospital, Republic of Korea E-PS-04-014
Rosai-Dorfman disease: cases report
Background & Objectives: Gastric type mucinous carcinoma (GMC) of the Y. Gulyaeva1, T.I. Nabebina1, A.T. Dubrovskij1
1
uterine cervix is difficult to recognize in cytologic specimens. These tumours National Cancer Centre, Belarus
are characterised by bland nuclear features and abundant mucin or goblet cell
differentiation, but clinically aggressive. GMC is not associated with human Background & Objectives: Rosai–Dorfman disease is a reactive histio-
papillomavirus (HPV) infection. We analysed cytologic features of GMC of cytic proliferation of unknown etiology characterised by a proliferation of
the uterine cervix compared to usual type endocervical adenocarcinoma. histiocytes with distinctive cytologic and immunophenotypic features.
Methods: We reviewed the cervical and ascites fluid smears from 3 Methods: We describe here two: one - with damage to the soft tissues and
patients with a pathologic diagnosis of GMC. All slides were convention- bones of the face and lymph nodes, the second - with damage to the CNS
ally smeared or liquid-based prepared (ThinPrep) and stained with and lymph nodes.
papanicoloau stain. Results: Histologically, lymph nodes are significantly enlarged. At low-
Results: Among three cases, the cytologic diagnoses were atypical glan- power magnification, the overall nodal architecture is generally maintained,
dular cells, favor neoplastic in two cases and adenocarcinoma in one case. and sinuses are distended by a proliferation of large histiocytes associated
High risk-HPV testing in these 3 cases was negative. Histologically, the with small lymphocytes and plasma cells. The lymph node parenchyma is
tumours consist of irregular angulated glands invading the cervical stro- characterised by follicular hyperplasia and plasmacytosis in interfollicular
ma. These cells were positive for MUC6 and p53, but negative for areas. Mitotic figures are rarely identified. the histiocytes are large and
p16. Cytologically, the tumour cells had bland nuclear morpholo- characterised by abundant eosinophilic cytoplasm, distinct cell borders, and
gy with low nuclear to cytoplasmic ratios and abundant mucinous a central round nucleus with a prominent nucleolus. These histiocytes also
cytoplasm. The characteristic features of GMC were honeycomb exhibit emperipolesis. At extranodal sites there are large histiocytes and
sheets, vacuolar or foamy cytoplasm with yellowish brown hue emperipolesis, the lesions are accompanied by fibrosis. Tumour cells demon-
due to mucin, intracytoplasmic neutrophil entrapment, and occa- strated the following immunoprofile: S-100+, CD68+, CD1a-.
sional small nucleoli, compared to usual type endocervical The patients with damage to the CNS received surgical treatment, both
adenocarcinoma. patients are under observation for six months after diagnosis.
Conclusion: Even though the case numbers are small, GMC may be Conclusion: The Rosai–Dorfman disease prognosis is excellent, with
recognized by cytologic features, such as honeycomb sheets of bland most patients being free of disease or with stable disease. However, some
tumour cells with abundant foamy cytoplasm with yellowish brown hue patients may develop recur-rent disease in the original site or other body
due to mucin. sites.

E-PS-04-013 E-PS-04-015
Colonic adenocarcinoma presenting with supraclavicular lymph Pitfall in urinarycytology - are non-neoplastic findings not relevant at
node metastasis: a rare case report all? - crystals versus parasites
H. Seneldir 1 , G. Kir 1 , B. Gucluer 1 , N. Ozbay 1 , A. Gapbarov 2 , A.M.G. Pereira1, C. Padrao1, F. Galante Pereira1, R. S. S. Oliveira1,
O. Alimoglu2 A.T. Alves2
1 1
Istanbul Medeniyet University, Department of Pathology, Turkey, Hospital Prof. Doutor Fernando Fonseca, EPE, Portugal, 2 Instituto de
2
Istanbul Medeniyet University, Department of General Surgery, Turkey Anatomia Patológica da Faculdade Medicina Universidade de Lisboa,
Portugal
Background & Objectives: In colorectal cancers, the most common
sites of metastasis are liver, lung and peritoneum. Non-regional lymphatic Background & Objectives: In an era so focused on cancer, sometimes
involvement in colon primary is an uncommon finding. we tend to disregard non-neoplastic findings that are important to
 Virchows Arch

1
diagnosis, treatment and clinical outcome of the patients. With these cases Department of Pathology and Laboratories, Hospital Universitario
we pretend to raise awareness for non-neoplastic findings in urine cytol- Fundación Santa Fe de Bogotá. Bogotá, Colombia, 2 Transplant and
ogy specimens namely the differential diagnosis between uric acid crys- Hepatobiliary Surgery Service, Hospital Universitario Fundación Santa
tals and parasites. Fe de Bogotá. Bogotá, Colombia, 3 Department of Pathology and
Methods: We report two cases of urinary cytology specimen’s analysis. One, Laboratory Medicine, Hospital Universitario Fundación Santa Fe de
referring to 77-years-old male patient in the context of follow up of high grade Bogotá. Bogotá, Colombia
urothelial cancer, and the other, referring to 86-years-old-female patient, on
etiological investigation of a non-lithiasic hydronephrosis. Background & Objectives: Cryoglobulinemia is a disease defined by
Results: Both cytologies had similar findings. On microscopic examina- the presence of abnormal proteins in blood that accumulate and become
tion, we identified some elliptical structures that seemed to be parasitic in insoluble at low temperatures. Clinically, it is a multisystemic entity with
nature. The objects were considerable smaller than eggs of Schistosoma cutaneous involvement due to purpuric lesions. It is classified as type I
haematobium, lacked a single terminal spine and had no miracidium (monoclonal) with the presence of intravascular deposits of cryoglobulin
which raised suspicion of a different structure. These objects appeared and type II (mixed) with acute vasculitis. We present a patient with a
to have a spine on both ends and were highly birefringent under polarized mixed cryoglobulinemia associated with hepatitis C virus infection.
light, making it possible to identify them as uric acid crystals. Methods: A 56-year-old male with a diagnosis of decompensated cirrho-
Conclusion: Crystals in urine cytology can present in various shapes and sis due to chronic Hepatitis C infection, hepatic encephalopathy, portal
sizes and uric acid crystals are one of the most variable, sometimes with hypertension, refractory ascites and renal dysfunction. During his hospi-
pointy extremities and multiple colors that be confused with parasite eggs, talization presented hemorrhagic purpuric and painful lesions
exogenous material or artifacts. It is especially important to avoid pitfalls compromising the lower limbs associated with decreased distal perfusion
and clarify the diagnosis of Schistosoma’s eggs because of its relation and blister on the right leg.
with squamous cell carcinoma of the bladder. Results: The skin biopsy revealed areas of necrotic epithelium, superfi-
cial perivascular mononuclear inflammatory infiltrate associated with
abundant extravasated erythrocytes, karyorrhexis around small vessels
E-PS-04-016 in the upper and middle dermis with fibrinoid necrosis of vascular walls,
Collecting duct carcinoma of the kidney diagnosed on fine needle abundant interstitial hemorrhage, deposits of hyaline material inside the
aspiration with distinctive cytomorphology: a case report with histo- vascular structures or fibrin thrombi. Such findings where compatible
logical correlation and literature review with necrotizing hemorrhagic leukocytoclastic vasculitis due to mixed
D. Pinto1, X. Qian2,3 cryoglobulinemia. Patient received pulses of methylprednisolone, plas-
1
Centro Hospitalar de Lisboa Ocidental, EPE, Portugal, 2 Brigham and mapheresis improved of skin lesions; however, with posterior anuria, and
Women's Hospital, USA, 3 Harvard Medical School, USA despite hemodialysis he died.
Conclusion: In the presence of an acute vasculitis, although there is no
Background & Objectives: Collecting duct carcinoma (CDC) of the presence of hyaline thrombi, it is important to raise the suspicion of mixed
kidney is a rare high-grade adenocarcinoma of the renal medullary region. cryoglobulinemia. We presented a case of Hepatitis C virus-related mixed
Its diagnosis is based on criteria proposed in the WHO 2016. Cytologic cryoglobulinemia.
features, however, are considered mostly non-specific. We report on a
case of CDC diagnosed by fine needle aspiration (FNA) cytology and
perform a literature review. E-PS-05-002
Methods: A relevant case was selected from our routine. Literature re- Cutaneous adenoid cystic carcinoma metastasizing to the lung 10
view was performed. years after the initial diagnosis
Results: 58-year-old man with history of collecting duct carcinoma of the S. Sotiriou 1 , M. Bobos 2 , D. Hatzibougias 2 , E. Michalopoulou-
kidney and follicular thyroid carcinoma. A mass of the left humerus was Manoloutsiou2 , E. Athanasiou2 , E. Goupou2, I. Boukovinas3 , S.
detected and submitted to FNA. Smears were moderately cellular and Galanis4, I. Kostopoulos1, T. Koletsa5
1
contained epithelial cells forming acinar clusters. Fragments of a Pathology Department, Faculty of Medicine, Aristotle University of
paucicellular fibroconjuctive tissue were identified. Cytology was high- Thessaloniki, Greece, 2 "Microdiagnostics" Ltd., Thessaloniki, Greece,
3
grade. Tumour cells were positive for CK7, CKAE1/AE3, FH, PAX8 and Bioclinic Thessaloniki, Greece, 4 "G. Papanikolaou" General Hospital,
SMARCB1 and negative for AMACR, AR, CK20, ERG, OCT3/4 and Thessaloniki, Greece, 5 Pathology Department, Medical School, Aristotle
TTF1. A diagnosis of metastatic CDC was made. University of Thessaloniki, Thessaloniki, Greece
Conclusion: The observed fibroconjunctive fragments are compatible with a
Background & Objectives: Cutaneous adenoid cystic carcinomas
desmoplastic stroma. Previous publications have shown these are part of the
(CACCs) are rare neoplasms, that most commonly arise in the scalp
morphologic spectrum of CDC on FNA cytology, but not specific. To make a
and metastasize to the lungs, even many years after the initial diagnosis.
specific diagnosis, we followed an algorithmic immunohistochemistry ap-
The aim of this case report is to raise awareness regarding this entity and
proach, excluding different primary locations, namely urothelial carcinoma,
to point the importance of the differential diagnosis, especially in the
and other distal nephron tumours showing a high-grade adenocarcinoma
context of metastatic disease.
morphology with a desmoplastic stroma. Diagnosing a specific entity is im-
Methods: In 2008 a 66-year-old man has undergone resection of a skin
portant not only to enable future studies of tumour genetics and pathogenesis,
nodule of the scalp, and ten years later (2018) has undergone a biopsy of a
but also to allow for appropriate therapy. This is possible on FNA cytology.
pulmonary lesion.
Results: Microscopically, the cutaneous lesion represented an infiltrating
Sunday, 8 September 2019 – Wednesday, 11 September 2019 carcinoma. The neoplastic cells were immunoreactive for AE1/AE3 and
E-PS-05 | Dermatopathology CD117, and arranged in tubular and cribriform formations, with an inner
luminal (highlighted with EMA) and an outer basal/myoepithelial cell
layer (highlighted with SMA). Perineural infiltration was prominent.
E-PS-05-001 The pulmonary lesion represented a carcinoma with similar morphology.
Hepatitis C-related liver cirrhosis associated with mixed Based on the histological and immunohistochemical findings, but also on
cryoglobulinemia the absence of other lesions, our final diagnosis was that of a CACC with
M. Rolon1, M. Tapias2, L. Barrera3, J. Alvarez-Figueroa3 pulmonary metastasis.
Virchows Arch

Conclusion: CACC must be differentially diagnosed from metastatic ACC, Results: The tumour was situated in superficial dermis and composed of
but also from primary cutaneous neoplasms with similar morphology, such as solid sheets of atypical rhabdoid cells with vesicular nuclei and nucleoli.
secretory, cribriform and adenoid basal cell carcinoma. A high level of sus- Mitoses were conspicuous. Tumour cells expressed INI1 and desmin in
picion is recommended whenever a patient with a history of CACC presents diffuse and strong fashion with focal expression of myoD1 and
a second lesion. Clinicopathological correlation is of paramount importance myogenin. All other immunohistochemical melanoma markers
in the differential diagnosis between primary and secondary ACCs. (SOX10, S100, HMB45, MelanA) were negative. In the surrounding
epidermis, remnants of a junctional and lentiginous atypical melanocytic
proliferation with pagetoid spread were identified, consistent with mela-
E-PS-05-003 noma in situ, with maintained SOX10 expression.
Eccrine angiomatous hamartoma - a seemingly benign lesion with an Conclusion: Melanoma with rhabdomyosarcomatous differentiation is a
unpredictable behaviour rare tumour that must be considered in differential diagnosis when deal-
A.C. Lisievici1, T.A. Georgescu2, A. Zota3, T. Tebeica4 ing with rhabdomyosarcoma of the skin, especially in elderly.
1
Carol Davila University of Medicine and Pharmacy, Bucharest, European Regional Development Fund-Project BBMRI-CZ: Biobank
Romania, 2 Department of Pathology, Bucharest Emergency University network – a versatile platform for the research of the etiopathogenesis
Hospital, Romania, 3 Department of Dermatovenerology, Dr. Leventer of diseases, No: EF16 013/0001674.
Centre, Bucharest, Romania, 4 Department of Pathology, Dr. Leventer
Centre, Bucharest, Romania
E-PS-05-005
Background & Objectives: Eccrine angiomatous hamartoma (EAH) A case of sebaceous carcinoma arising on the wrist - an atypical
represents a rare nevocytic malformation composed of sweat gland and location for an uncommon neoplasm
mesenchymal elements including blood vessels and smooth muscle, M. Kilmpasani 1 , I. Karafoulidou 1 , A. Baliaka 1 , N. Pastelli 1 , Z.
which usually occurs in children. Most cases of EAH reported in the Tzimorota2, S. Papaemmanouil1
1
literature had an indolent behavior and did not recur, except for 2 cases Department of Pathology, General Hospital of Thessaloniki "G.
from a retrospective study. Another case report presented a patient with Papanikolaou", Greece, 2 Department of Plastic, Reconstructive and
localized severe pain, which warranted partial amputation of the affected Hand Surgery, General Hospital of Thessaloniki "G. Papanikolaou",
finger. Greece
Methods: We report the case of a 22–year-old male who presented a few
years ago in another center with a red plaque on his inner thigh, that Background & Objectives: Sebaceous carcinoma is an uncommon cuta-
incresed in size and became tender in the past few months. The lesion neous malignant neoplasm, often misdiagnosed as a benign lesion or a basal
was surgically excised and diagnosed as cavernous hemangioma. Two cell carcinoma. It is most commonly found on head and neck, mainly at
years later, the lesion recurred and the initial histopathological specimen periocular sites. The extremities are an atypical location for an extraocular
was referred to our clinic for second opinion. sebaceous carcinoma. We report the case of a 78-year-old patient with a
Results: Histopathological examination revealed a proliferation of blood tumour on the right wrist, reportedly existent for at least 2 years.
vessels in close relation with the epidermis, focally mimicking Methods: Following excision, the protruding tumour measured 2.3cm,
angiokeratoma. However, a significant number of sweat glands and and demonstrated a tan-pink cut surface. It was examined in FFPE sec-
smooth muscle fibers were intermingled between the vascular structures. tions with hematoxylin-eosin and immunohistochemical stains.
The lesion was diffusely infiltrating both reticular dermis and hypodermis Results: The neoplasm consisted of cells with multivacuolated, clear
and was covered by hyperplastic epidermis with verrucous features. cytoplasm and oval nuclei. They formed well-demarcated, solid nests in
Lateral excision was incomplete. a desmoplastic, highly vascularized stroma, with the presence of comedo-
Conclusion: EAH is a rare lesion with unusual behavior, which can be type necrosis and vascular neoplastic emboli. A high mitotic activity was
easily misdiagnosed due to the bland appearance of its components. prominent, including mainly atypical mitoses.
Simple excision is usually curative, but recurrences, although rarely re- The overlying epidermis showed areas of low-grade dysplasia with hy-
ported in the literature, are possible and warrant increased awareness for perkeratosis and parakeratosis, while the adjacent epidermis demonstrat-
practicing pathologists and clinicians. Therefore, in such lesions, close ed independent foci of full-thickness, dysplastic epithelium, with evident
follow up is recommended. parakeratosis.
The final diagnosis was sebaceous carcinoma of the skin, grade I, with
coexisting, multiple foci of in situ carcinoma in the adjacent skin.
E-PS-05-004 Conclusion: An intraepidermal growth pattern is seen more often in
Dedifferentiated melanoma with rhabdomyosarcomatous periocular sebaceous carcinoma and less commonly at extraocular sites. A
transdifferentiation - a rare case report grading system based on growth pattern has been proposed; moreover, vas-
J. Soukup1,2, M. Manethova1,2, L. Krbal1,2 cular invasion, persistence of symptoms longer than 6 months and size larger
1
The Fingerland Department of Pathology, University Hospital Hradec than 10mm, among others, also seem to be related with an adverse progno-
Kralove, Czech Republic, 2 Charles University Faculty of Medicine in sis. Given the above, our case demonstrates some interesting features.
Hradec Kralove, Czech Republic

Background & Objectives: Dedifferentiation in melanoma is an unusual E-PS-05-007

phenomenon, characterised by loss of normal immunohistochemical profile The curious case of an anal polyp that turned out to be
and morphology. Some of these tumours may show a divergent differentiation lymphangioma circumscriptum: a case report
including rhabdomyosarcomatous. Such cases are exceedingly rare, with less A.D. Plopeanu1, A. Dema2, S. Olariu3, S. Taban1,4
1
than 12 cases reported. Here we present an additional case. Emergency Clinical County Hospital "Pius Brinzeu" Timisoara,
Methods: 84-year-old male presented with a skin tumour of a right arm. Romania, 2 Department of Pathology, Emergency Clinical County
Excision measuring 55 x 35 x 12 mm with the tumour measuring 35 x 35 x Hospital "Pius Brinzeu", Timisoara, Romania, 3 Emergency Clinical
8 mm was retrieved. Histopathologic evaluation and immunohistochemical County Hospital "Pius Brinzeu" Timisoara, "Victor Babes" University
staining for SOX10, S100, HMB45, MelanA, CD30, CD45, CD56, CD117, of Medicine and Pharmacy Timisoara, Department of Surgery,
CK AE1/3, CK18, CK20, BER-EP4, p63, SMA, INI1, synaptophysin, ERG, Romania, 4 ''Victor Babes'' University of Medicine and Pharmacy
desmin, myoD1, myogenin and BRAF V600E was performed. Timisoara, Department of Pathology, Romania
 Virchows Arch

Background & Objectives: Lymphangioma circumscriptum is a rare especially useful when dealing with atypical lesions, like those limited
benign tumour consisting of abnormal ectatic lymph vessels involving to the hypodermis and mimicking a panniculitis.
the upper part of the dermis. This infrequent lesion appears with predi-
lection on the extremities, trunk and axilla. The best course of treatment is
not well established. Although considered the most effective, surgery is E-PS-05-009
associated with a high risk of complications. The aim of this case report is ALK-positive atypical spitz tumour: report of two cases and brief
to highlight the possibility of diagnosing an uncommon lesion with a review of the literature
localization rarely mentioned in the specialty literature. C. Ricci1, A. De Leo2, G. Santandrea3, B. Corti2
1
Methods: We report the case of a 35 years old woman who was operated Department of Biomedical and Neuromotor Sciences, Bellaria Hospital,
on for external hemorrhoids and an anal polyp. The microscopic exami- Bologna, Italy, 2 University of Bologna, Department of Surgical pathol-
nation revealed the polyp to be a benign vascular tumour and further ogy, Italy, 3 Pathology Unit, S. Orsola-Malpighi Hospital, University of
immunohistochemistry tests were performed in order to confirm the Bologna, Bologna, Italy
diagnostic.
Results: The histopathological examination revealed an achanthotic Background & Objectives: Spitz tumours (STs) are a subgroup of
and hyperparakeratotic epithelium, with numerous dilated vessels in melanocytic neoplasms ranging from Spitz nevus (SN) to atypical Spitz
the papillary dermis, vessels that in hematoxylin-eosin staining ap- tumours (ASTs) and spitzoid melanoma (SM), the latter with capacity of
peared to be lymphatic. In order to confirm the diagnosis, further metastasis and lethal outcome. In the last years molecular investigations
immunohistochemical examination were carried out. The vessels played a central role in the sub-characterization of STs. In particular, ALK
were proven to be lymphatic by being positive for D2-40 and fusion has been noticed in 10% of STs, including 5% of ASTs and 1% of
CD31 antibodies, allowing us to give a positive diagnostic for SMs. Herein, we report two cases of ALK-positive ASTs (ALK-ASTs)
lymphangioma circumscriptum. arose during adolescence.
Conclusion: Lymphangioma circumscriptum is a rare tumour involving Methods: The first patient was a 16-year-old boy with a lesion on the
the lymphatic vessels in the dermis and despite its infrequent nature, it right leg; the second one was a 14-year-old boy with a lesion on the right
must be taken into account for differential diagnosis, even when foot over the previous months. Immunoistochemistry (IHC) for HMB45,
appearing in an unusual topographic area. MART1, S-100, Ki67, ALK, p16 and BAP1 was performed.
Results: In both cases, histology revealed a wedge-shaped proliferation
of atypical spindle, epithelioid and multinucleated melanocytes, arranged
E-PS-05-008 in a plexiform pattern in deep dermis. Mitoses were present (≤ 4/mm2),
A 3-year retrospective study demonstrating an important histopath- even deep/marginal. Tumour cells were strongly positive for S-100, p16
ologic clue for diagnosing cutaneous Rosai-Dorfman disease and ALK1; Ki-67 was low and BAP-1 maintained. A diagnosis of ALK-
A.C. Lisievici1, T.A. Georgescu2, A. Rizoiu3, A.M. Stanciu4, T. Tebeica5 AST was rendered. Both patients underwent a sentinel lymph-node biop-
1
Carol Davila University of Medicine and Pharmacy, Bucharest, sy and, in the first patient, we found subcapsular ALK-positive tumour
Romania, 2 Department of Pathology, Bucharest Emergency University clusters. In both cases, no recurrence or disease progression were
Hospital, Romania, 3 Department of Dermatovenerology, MEDINVEST, detected.
Bucharest, Romania, 4 Department of Dermatovenerology, Dr. Leventer Conclusion: Our report confirms that ALK expression identifies a bio-
Centre, Bucharest, Romania, 5 Department of Pathology, Dr. Leventer logically and morphologically distinct subcategory of ASTs, unrelated to
Centre, Bucharest, Romania the other variants. Further investigations are needed to clarify the prog-
nostic meaning of these findings.
Background & Objectives: Cutaneous Rosai-Dorfman disease is a rare
non-lymphoid cutaneous infiltrate of unknown etiology. It is currently
acknowledged that skin lesions may represent the sole manifestation of E-PS-05-010
Rosai-Dorfman disease, although involvement of both skin and lymph The role of the pathologist in the Mohs micrographic surgery: a
nodes is much more frequently encountered. Histologically, it is retrospective study
characterised by an abundant inflammatory infiltrate, in which numerous I. Español1, I. Trias1, M. Alegre2
1
histiocytes are identified, some of them showing classic emperipolesis. Hospital Plató. Pathology DP, Spain, 2 Hospital Plató. Dermatology,
Immunohistochemically, the large histiocytes express both S100 and Spain
CD68, but are negative for CD1a.
Methods: This is a retrospective study including all cutaneous Rosai- Background & Objectives: Transplant glomerulitis is a key feature of
Dorfman diseases that were diagnosed in our Dermatopathology unit antibody-mediated rejection. Leukocytes occluding the glomerular capil-
during a period of three years (2016-2018). Clinical information was laries define its morphological pattern. It is difficult to recognize and its
retrieved from the virtual database. We thoroughly re-examined all scoring only has a fair interobserver agreement. We aimed to determine
Hematoxylin-Eosin and immunohistochemically stained slides, aiming and validate a well reproducible immunohistochemical marker for
to establish clinico-pathological correlations. Ancillary studies included: glomerulitis, and looked at its prognostic value.
S100, CD68, CD1a, CD79a, CD30. Methods: Receiver operator curves (ROC) using CD3, CD45, or CD68
Results: Clinically, the face and the trunk were involved equally often, positive cell counts in the glomeruli of kidney transplant biopsies with
while the extremities and the buttocks were less affected. 50% of all cases glomerulitis or without relevant pathology were used to determine cut-
presented as nodules, 25% presented as indurated plaques with subcuta- offs. Findings were independently validated, tested for interobserver
neous nodules and 25% cases mimicked a panniculitis. 62.5% of all agreement, and compared to other rejection patterns. The prognostic val-
patients had solitary lesions, while 37.5% presented with multiple nod- ue was investigated in a cohort of patients (n=95) transplanted in the
ules. Histologically, all cases presented an inflammatory reaction in presence of donor-specific antibodies (DSA).
which plasmocytes abounded and bordered the infiltrate. This feature Results: A cut-off >5.5 CD68 positive cells in the most affected glomer-
was more than once, the first clue to this diagnosis. ulus (CD68max) resulted in an area under the curve (AUC) of 0.966.
Conclusion: In our opinion, an abundant plasma cell infiltrate that sur- CD68max correlated with the percentage of glomeruli with CD68 counts
rounds a diffuse lympho-histiocytic infiltrate is highly suggestive for this above the cut-off (ρ = 0.875). Three risk groups (baseline, low, high) with
entity and an important clue that should warrant a thorough analysis of the prognostic impact on graft survival were established using ROC compar-
slide, in order to find characteristic emperipolesis. This sign can be ing cases with glomerular Banff scores 0 vs. 1 (AUC = 0.891, cut-off >
Virchows Arch

3.9 % of glomeruli) and 1 vs. 2-3 (AUC = 0.867, cut-off >64.4 %). Methods: A 78-year-old male patient presented to the clinic with the
Interobserver agreement was good and independent of the level of exper- ulcerated nodular lesion at the parietal region of the scalp. The lesion
tise. In the DSA positive cohort, the risk groups proved to be an early and was totally excised. In microscopic findings, we identified a tumour
independent prognostic marker of poor graft function. which showing infiltration as single cells and cell groups in the myxoid
Conclusion: Addition of a CD68 stain to the routine analysis of kidney stroma of dermis and also causes ulceration in the epidermis. The depth of
transplant biopsies provides additional diagnostic and prognostic infor- invasion of thetumour was 0.3 cm and the diameter of the tumour was
mation. 0.7 cm (stage pT1). In immunohistochemistry tumour cells showed pos-
itivity for pan-cytokeratin (AE1/AE3), p40, vimentin and negativity for
S-100, HMB-45, MART1, SMA, desmin.
E-PS-05-011 Results: The diagnostic criteria of MSC SCC in the literature are the
Cutaneous microcystic/reticular schwannoma determined inciden- significant myxoid stromal changes, observing these changes onmore
tally in pilonidal sinus specimen: a case report than half of the lesion, positive staining of neoplastic spindle (and squa-
R. Bedir1, S. Orhan2, F.G. Gülname2 mous) cells with minimum one cytokeratin and negative staining with
1
Recep Tayyip Erdogan University Deparment of Pathology, Turkey, melanocytic and mesenchymal markers. Based on these results, the case
2
Department of Pathology, Recep Tayyip Erdogan University, Medical was diagnosed with MSC SCC. The myxofibrosarcoma, malign periph-
Faculty, Turkey eral nerve sheath tumour, spindle cell atypical fibrocarcinoma and spindle
cell melanoma should always be considered in the differential diagnosis
Background & Objectives: Schwannoma is a common, slow-growing, of MSS SCC.
encapsulated and usually asymptomatic benign peripheral nerve sheath Conclusion: The differential diagnosis of MSC SCC’s should be made
tumour. Microcystic/reticular schwannoma (MRS) is a very rare histolog- by using melanocytic and mesenchymal markers in order to distinguishit
ical variant of schwannoma. MRS is a recent addition to this group of from all other potential tumours. The diagnosis should be confirmed by
tumours, which have a predisposition for visceral organs. Unlike typical using epithelial markers.
morphology of schwannomas, it shows no Antoni A, Antoni B areas or
Verocay bodies. Here, we present the case of a 28-year-old male who has
an incidentally detected cutaneous MRS in pilonidal sinus specimen. E-PS-05-013
Methods: The specimen was fixated with 10% buffered formalin and Minimal deviation melanoma: a rare case study report
were processed by conventional histopathological methods using paraffin D. Anestakis1, M.I. Givannakis2, P. Konstantinidou1, F. Louka1 ,
embedding, sectioning and Hematoxylin-Eosin staining. E. Zagelidou3
1
Results: A 28-year-old male patient presented with anintermittent painful Department of Autopsy Histopathology, Lab. of Forensic Medicine and
swelling in the anogenital region. The clinical impression was a pilonidal Toxicology, Aristotle University of Thessaloniki, Greece, 2 Surgical
sinus and it is surgically removed. Macroscopic examination revealed a sinus Department , General Hospital "AHEPA", Thessaloniki Greece,
3
tract and nearby mass under the skin with a gray-white solid cut surface Thessaloniki Forensic Service, Thessaloniki, Greece
showing focal myxoid appearance which is found incidentally. Mass mea-
sured 2x1.5 cm, and it was well circumscribed with lobular appearance. Background & Objectives: Minimal deviation melanomas, also called
Microscopic examination revealed spindle-shaped neoplastic cells which borderline melanocytic lesion, are uncommon nevomelano-cytic tumours
have scant eosinophilic cytoplasm and bland hyperchromatic round to oval of indeterminate risk that appear as pigmented or non-pigmented skin
nuclei. There is no mitotic figures, cytological atypia or necrosis. The tumour nodules. They are typically lesions that satisfy the requisites for vertical
cells were forming lace-like, retiform or pseudoglandular structures contain- growth. In borderline variants, they form an expansile nodule that is
ing abundant basophilic myxoid material. The tumour showed strongly dif- confined to a widespread papillary dermis. If they form an expansile
fuse positivity for S-100 protein, vimentin, and GFAP while negative for nodule and infiltrate the reticular dermis, they are minimal deviation
CD34, pan-CK (AE1/AE3), HMB-45 and EMA in immunohistochemical melanomas without the borderline qualification. They differ cytologically
staining. Finally the case was diagnosed as cutaneous MRS. from the common aggressive melanomas.
Conclusion: Schwannomas are benign tumours which arise from the Methods: This report describes a case of minimal deviation melanomas
cells of Schwann that form the neural sheath. There are several morpho- involving on the scalp in a 72-year-old man. The patient presented with a
logic variants of schwannoma, including cellular schwannoma, ancient skin nodule of scalp, simple excision of the tumour was performed.
schwannoma, plexiform schwannoma, epithelioid schwannoma, glandu- Results: Histological and the immunophenotype findings were compat-
lar schwannoma, melanotic schwannoma, hybrid schwannoma/ ible with minimal deviation melanoma. In the follow-up, after three years
perineurioma and microcystic/reticular schwannoma. MRS is a very rare no recur or metastasis appeared. In the follow-up, after three years no
variant of schwannomas with benign biological behaviour. Both surgeons recur or metastasis appeared.
and pathologists should consider MRS in the differential diagnosis of soft Conclusion: In our experience, they may rarely recur or rarely metasta-
tissue tumours with a reticular growth pattern. size. These tumours are mostly observed in young adults and older chil-
dren and are clinically diagnosed as Spitz nevi, hemangiomas, or malig-
nant melanomas. It may originate from a pre-existing mole, or from
E-PS-05-012 normal skin (a new growth type). Minimal Deviation Melanoma of
Primary cutaneous myxoid spindle cell squamous cell carcinoma of Skin tumours is said to have a ‘borderline’ behaviour. The most common
the scalp: a case report treatment is surgery. Tumour metastasis is not observed very often and
M. Suntur1, O. Semerci1, R. Bedir1 recurrences are uncommon after surgery.
1
Recep Tayyip Erdogan University, Department of Pathology, Turkey,

Background & Objectives: The primary cutaneous squamous cell E-PS-05-014

carcinoma (SCC) is the second most common skin cancer. Muir-Torre Syndrome: a rare hereditary condition
Primary cutaneous myxoid spindle cell squamous cell carcinoma C. Faria1, M.J. Julião1, V. Almeida2, F. Ramalhosa1, J. Fraga1, A. Lai1,
(MSC SCC) is an extremely rare variant of SCC with only 7 R. Almeida 3,4 , M.B. Pimentão 1 , H. Moreira 3 , R.C. Oliveira 1 ,
cases reported in the literature. Here, we present an MSC SCC case M.A. Cipriano1
1
located at the scalp of a 78-year-old male patient and its differential Centro Hospitalar e Universitário de Coimbra, Portugal, 2 Institute of
diagnosis with immunohistochemical results. Anatomical and Molecular Pathology, Faculty of Medicine of the
 Virchows Arch

University of Coimbra, Portugal, 3 Centro Hospitalar e Universitário de at the time of biopsy. The treatment of it is surgical excision and sometimes
Coimbra - Pathology Department, Portugal, 4 Faculty of Medicine in adjuvant radiotherapy and/or chemotherapy. Immunotherapy and targeted
Coimbra, Portugal therapies are the other treatment methods which have been investigated.

Background & Objectives: Muir-Torre syndrome, a rare autosomal

dominant condition, is caused by germline mutations in the DNA mis- E-PS-05-016
match repair (MMR) genes, MLH1, PMS2, MSH2 and MSH6 Cutaneous infiltrate of a B chronic lymphocityc leukemia in two
genes. This syndrome is considered a phenotypic variant of he- patients with an atypical fibroxanthoma and squamous cell carcino-
reditary nonpolyposis colorectal carcinoma syndrome (HNPCC, ma: two case reports and review of the literature
Lynch syndrome) and is characterised by the association of at A. Sobrino Prados1, C. Yus Gotor2, N. Torrecilla Idiope2, M.J. Viso
least one sebaceous skin tumour and/or keratoacanthoma and at least Soriano1 , J.I. Franco Rubio 2 , H.P. Almanzar Comas 1 , S. Bakali
one visceral malignancy. Badesa1, R.I. Bermudez Cameo1, î Arellano Álvarez1, N. Estrada
Methods: We describe the case of a 49-year-old woman with a previous Mallarino1, B. Cazaña Pèrez2, M. Pastor Adiego2
1
diagnosis of pancreatic carcinoma in 2015 and with a right inferior pal- Hospital Universitario Miguel Servet Zaragoza, Spain, 2 Hospital
pebral lesion of rapid growth developed three years later. Universitario Miguel Servet, Spain
Results: Histopathological examination revealed a sebaceous skin neo-
plasia with lobulated pattern, composed by two cellular populations, one Background & Objectives: Cutaneous infiltrate of a B chronic
central with a clear cytoplasm and a monotonous nucleus, and a second lymphocityc leukemia (B-CLL) is an infradiagnosed condition, in which
population of peripheral basaloid cells. The stroma is scant and edema- clinical data and a methodic sample analyse is needed for making a
tous with congestive blood vessels. The mitotic activity is low and there correct diagnosis. Reviews in the literature suggest neoantigens and cy-
were not areas of tumour necrosis. tokines recognition and an immunosupressive microenvironment might
Immunohistochemistry study showed positivity for EMA and negativity explain the cause of the association of B-CLL and cutaneous neoplasms.
for CEA; with immunoreaction for Ki67 limited to the basal cell layer. Methods: Two 82-and-83-years-old-patients presented two lesions (0,9 and
The neoplastic nucleus also retained positivity for MLH1 and PMS2 and 1,2 cm size) in sun-exposed skin, which were completely excided, in 2018 in
had complete loss of MSH2 and MSH6. Hospital Universitario Miguel Servet in Zaragoza. Both suffered from a B-
Conclusion: The diagnosis is a sebaceous adenoma with microsat- CLL for years, with lymphocytosis as the only clinical manifestation.
ellite instability that is related to germline mutation of Muir-Torre Results: The H-E sections showed an atypical fibroxanthoma (AFX) and
syndrome. Particularly this patient was previously diagnosed with a squamous cell carcinoma (SCC) surrounded by an homogeneous infil-
a pancreatic ductal carcinoma although the internal malignancies trate of mature B lymphocytes, which stained for CD20, CD79 a, CD5
most frequently associated with this syndrome are colorectal, and CD23. Therefore, patients were diagnosed of an AFX and SCC
ggynaecological and urothelial cancers. So genetic testing and respectively with a cutaneous infiltration by B-CLL.
preventive cancer screening program alongside clinical criteria Patients with B- CLL have an increased risk of devoloping neoplasms,
should be studied for these patients. probably due to the immunosupresive environment caused by the B-CLL.
Besides, neoplasic lymphocytes infiltrate more frequently tumours or
other inflammatory conditions taking place in the skin. The most com-
E-PS-05-015 mon neoplasms associated with B-CLL are SCC, basocelular carcinoma
A rare lesion of ear; Merkel Cell Carcinoma and actinic queratosis. These have a higher risk of recurrences and it is
S.Y. Celik1, O. Ilhan Celik1, Y. Dere1 recommended the surgical margins to be wider.
1
Mugla Sitki Kocman University, Faculty of Medicine, Department of Conclusion: Further research is necessary for improving our knowledge
Pathology, Turkey about the etiopathogenic mechanisms and the prognosis they may have
and therefore, provide the best treatment options to patients.
Background & Objectives: Merkel Cell Carcinoma(MCC) is a rare,
aggressive, cutaneous neuroendocrine neoplasia with a high mor-
tality rate. It is generally seen in sun-exposed skin of head, neck E-PS-05-017
and extremities in older adults with light skin. It may present at Stepwise progression of proliferating pilar tumour and trichilemmal
an earlier age in immunocompromised individuals like HIV- carcinoma from pilar cysts is associated with p53 loss: a case report
infected patients, organ transplant recipients and patients with he- L. Ahmed1, R. Hejmadi1, M. El-Shafie1, K. Kok2, O. Cain1
1
matologic diseases. University Hospitals of Birmingham NHS Trust, Cellular Pathology
Methods: A 71-year-old male suffering from a rapidly growing, Queen Elizabeth Hospital, United Kingdom, 2 University Hospitals of
5cm, fixed, subcutaneous, nodular mass on his left auricle was Birmingham NHS Trust, Plastic and Burns department, Queen
referred to oto-rhino-laryngology clinic. An incisional biopsy Elizabeth Hospital, United Kingdom
demonstrated a necrotic tumour composed of small, uniform,
round cells with high nucleus-to-cytoplasm ratio, round vesicular Background & Objectives: Pilar (trichilemmal) cysts are commonly
nuclei with ‘salt and pepper’ chromatin, scarce cytoplasm and encountered specimens in routine diagnostic practice and only very rarely
high mitotic index. show atypical features. There is some debate as to whether stepwise
Results: Tumour cells were positive for Cytokeratin20, chromogranin A, molecular changes accumulating in pilar cysts gives rise to proliferating
Neuron-specific-enolase and synaptophysin and negative for pilar tumour and trichilemmal carcinoma, or whether these tumours de-
Cytokeratin7, CD45, TTF-1, s100, Desmin, Myogenin, p63, Melan A. velop de novo in the absence of a pre-existing pilar cyst.
Ki67 index was about 50%. The lesion was diagnosed as MCC. Later the Methods: We present a case of a patient with seventeen scalp cysts
tumour is completely excised and ipsilateral lymph nodes of the neck removed in one large surgical excision. Histologically all showed
were dissected. Three of the lymph nodes were metastatic. trichilemmal differentiation, ranging from benign pilar cyst, through pro-
Radiotherapy was added to the surgical treatment. liferating pilar tumour to trichilemmal carcinoma.
Conclusion: MCC is a very rare, aggressive tumour of epithelial and neuro- P53 immunohistochemistry was performed on the tumour.
endocrine origin that usually presents as a painless, exophytic nodul with a Results: We were able to demonstrate loss of p53 expression on immu-
poor prognosis, including high rates of metastasis, recurrence and mortality. nohistochemistry specifically in the malignant element. In contrast, non-
As it forms a banal-appearing lesion, the diagnosis of MCC is rarely suspected malignant elements showed patchy wild-type staining.
Virchows Arch

Conclusion: This case supports the hypothesis that stepwise molecular was subjected to surgical excision and the specimen was sent to the
changes result in the development of proliferating pilar tumour and Department of Pathology for histopathological examination.
trichilemmal carcinoma from pilar cysts. In keeping with previous stud- R e s u l t s : M i c r o s c o p i c a l l y, t h e t u m o u r w a s c o m p o s e d o f
ies, p53 mutation may well be a critical step in this progression detectable interanastomosing cord-like sheets of plump epithelial cells with vesicu-
by routine immunohistochemistry. lar and hyperchromatic nuclei forming pseudolumina and hobnail as-
pects. No foci of squamous differentiation or clear derivation from the
surface epithelium were observed. Tumour cells were diffusely positive
E-PS-05-018 for AE1/AE3, CK5/6, p63 and Vimentin and completely negative for
Aleukemic neonatal leukemia cutis preceding monocytic leukemia SMA, desmin, myogenin and S-100. In contrast to angiosarcoma, the
with a favourable outcome tumour cells were also invariably negative for endothelial cell markers
B. Sirine1, J. Pourchet1, S. Fraitag2, N. Sturm1, H. Gil1 such as factor VIII-related antigen, CD31 and CD34.
1
Grenoble Alpes University Hospital, France, 2 Enfants Malades Necker Conclusion: Based on the clinical, morphological and immunohisto-
Hospital, France chemical aspects, the final diagnosis of pseudovascular squamous cell
carcinoma has been established. Although the general outcome of this
Background & Objectives: Leukemia cutis(LC)is defined by cutaneous particularly rare variant is not very well studied, its recognition is ex-
infiltration by leukemic cells.In aleukemic LC,the invasion of the skin hap- tremely important due to the potential confusion with angiosarcoma,
pens at least 1 month before the acute leukemia.The neonatal form of LC which yields a completely different clinical outcome.
which occurs within 4 weeks of life is less frequent than adult LC.Neonatal
leukemia has a poor prognosis usually fatal.We report an exceptional case of
complete remission after aleukemic LC preceding acute leukemia with main E-PS-05-021
objectives to describe epidemiologic,clinical,histological,molecular and prog- Subcutaneous atypical ossifying fibromyxoid tumour with dermal
nostic features of aleukemic neonatal LC. involvement and mosaic loss of INI-1 expression: a case presentation
Methods: A female newborn presented at birth for a few firm red- P.I. Stinga1, A. Cioroianu1, S. Iacob2
1
violaceous papulo-nodular lesions in the face and the trunk.Physical ex- Colentina University Hospital, Romania, 2 Personal Genetics, Romania
amination didn’t reveal other abnormalities.CBC and coagulation tests of
umbilical cord blood and in the first 24 hours were normal.Cutaneous Background & Objectives: Ossifying fibromixoid tumour(OFT) is a
biopsy performed on 3rd day of life showed a dense dermal infiltrate rare soft tissue tumour with unusual dermal involvement, of uncertain
composed of a monomorphous undifferentiated blast cells with nuclear lineage of differentiation, harboring particular histological and immuno-
dust. These cells stained positively for CD4,CD15,CD68,CD43,HLA- histochemical features, as well as newly discovered molecular signatures.
DR.Myeloperoxidase was negative.Molecular testing revealed rearrange- Three subtypes have been described-typical,atypical,malignant, based on
ment of the MLL gene with translocation t(9;11). cellularity,nuclear grade,mitotic index. Owing to its rarity,this entity poses
Results: We concluded to a cutaneous monocytic leukemia cutis (AML- vexing diagnostic challenges.
M5).Thirteen days later,cerebrospinal fluid examination and bone marrow Methods: We present the case of a 48 year-old male patient with a 7 years
aspirate were normal, however, the peripheral blood smears showed the pres- clinical course of a 60mm superficial subcutaneous mass of the
ence of monoblasts(14%).A close biological follow-up was mandatory.On trunk(subscapular region), diagnosed elsewhere as extraskeletal myxoid
the 31th day of life,the patient presented anemia, hyperleukocytosis(54,6x109/ chondrosarcoma.
L),elevated blasts(28%)and monocytes(18%).Urgent administration of multi- Microscopy revealed a well-circumscribed,multinodular proliferation, arising
ple drug induction chemotherapy(ELAM 02 protocol)was followed by com- in the subcutis, focally extended into the deep dermis, compound of
plete remission and clearance of cutaneous lesions on day 28 of life. small,round to spindle-shaped, mild pleomorphic cells with vesicular nuclei,
Conclusion: LC is common in the ALM-M5 leukemia but its neonatal eosinophilic cytoplasm, arranged in cords/trabeculae/clusters, imbedded in an
form has very rarely been described.Neonatal LC without other clinical fibromyxoid matrix, surrounded by a peripheral shell of lamellar bone;the
signs has been reported in a few patients.Cutaneous biopsy and molecular cellularity was classified as intermediate and the mitotic index was
testing is mandatory for diagnosis and typing of the disease.The 3/50HPFs. The immunohistochemical study revealed S100 diffuse positivity
favourable outcome of our patient is exceptional. and focal GFAP, SMA,NSE,CD56 positivity; others markers
performed(CD34,EMA,Desmin) were negative. INI-1 stain showed mosaic
pattern staining. A diagnosis of an atypical OFT was made.
E-PS-05-019 Results: Molecular testing was elsewhere done, the result sustaining the
Pseudovascular squamous cell carcinoma: case report of an elusive diagnosis of OFT.On subsequent follow-up, the patient is alive and well,
entity and potential diagnostic pitfall without signs of recurrence or metastasis after 1 year from the surgery.
T.A. Georgescu1, A.C. Lisievici2, A. Dumitru3, M. Sajin4,5,6, M. Costache3,7 Conclusion: OFT is a peculiar neoplasm, often located in the superficial-
1
Department of Pathology, Bucharest Emergency University Hospital, ly soft tissue, with infrequent dermal involvement and potentially aggres-
Romania, 2 Carol Davila University of Medicine and Pharmacy, Bucharest, sive behavior, recently included in the group of translocation-related le-
Romania, 3 Department of Pathology, "Carol Davila" University of Medicine sions; the entity should be taken in consideration in the differential diag-
and Pharmacy, Bucharest, Romania, 4 SUUB, Romania, 5 UMF Carol Davila, nosis of the superficial soft tissues tumours, often encountered in
Romania, 6 European Society of Pathology, Romania, 7 Department of dermatopathology practice.
Pathology, Emergency University Hospital Bucharest, Romania
This work was supported by a grant of Romanian Ministery of Research
Background & Objectives: Pseudovascular squamous cell carcinoma and Innovation, CCCDI-UEFISCDI, project number 61PCCDI⁄2018 PN-
was initially described in 1992 by Nappi, Barnejee and their collabora- III-P1-1.2-PCCDI-2017-0341, within PNCDI-III.
tors, as a rare variant of cutaneous acantholytic squamous cell carcinoma
which occurs on sun-exposed areas of middle-aged or elderly patients and
can easily be mistaken histologically for angiosarcoma or an ulcerated E-PS-05-022
metastasis of adenocarcinoma. Melanocytic matricoma: a case report of a rare entity
Methods: We present the case of a 78-year-old male presenting to our G. Morgantetti1, G.A. Medeiros1, S.B.G. Hosseini1, M.L. Balancin1,
clinic with an exophytic tumour of 12/7/5mm with extensive surface M.E.d.A.S. Yamashita2
1
erosion, located on the left thigh. After clinical examination, the patient University of Sao Paulo, Brazil, 2 Barretos Cancer Hospital, Brazil
 Virchows Arch

Background & Objectives: Melanocytic matricoma is a rare form of Results: Histopathology revealed extensive lichenoid changes with
pigmented follicular neoplasm with both matrical and melanocytic intraepidermal bullae. Atypical lymphocyte infiltration was present at
components, first reported in 1999 by Carlson et al. Since its first the dermoepidermal junction, in bulla.
publication, few cases have been published in the current scientific Conclusion: Although mycosis fungoides bullosa is extremely rare, it is
literature. Usually associated with hyperpigmented lesions regarded as an important clinical subtype of cutaneous T-cell lymphoma.
appearing at sun-damaged skin of adults, melanocytic matricoma Mycosis fungoides bullosa represents an aggressive form of mycosis
is rarely listed as the most probable diagnosis based on clinical fungoides and is associated with a poor prognosis.
examination alone, due to its very low incidence and lack of patho- Mycosis fungoides bullosa is a rare occurance which is always manifest-
gnomonic epidemiologic, clinical or dermathoscopic aspects. ed in vesiculobullous eruptions. We describe a 75-year old man with
Microscopically, the lesion consists of a well circumscribed histopathologic diagnosis of mycosis fungoides bullosa who developed
hypercellular nodule composed of a biphasic cell population: an plaques lacking blister formation on normal appearing skin.Our case is
epithelial phase composed of both matrical and supramatrical cells rare in the literature with the incompatible clinical and histological diag-
with clustered shadow cells and a melanocytic one, composed of nosis of the rare variant ‘mycosis fungoides bullosa’.
dendritic melanocytes. The main clinical differential diagnoses are
hemangioma, pigmented basal cell carcinoma and melanoma, while
the main histopathological pitfall resides in the differentiation of E-PS-05-024
melanocytic matricoma with matricoma or pigmented Cutaneous biphasic sarcomatoid basal cell carcinoma: report of a
pilomatricoma. The present report aims to contribute with the cur- rare entity and review of the literature
rent clinical, histological and immunohistochemical knowledge of M. Mellouli1, S. Graja1, S. Makni1, N. Gouiaa1, A. Ben Mabrouk1, Z.
the disease. Lajmi1, M. Zghal1, M. Walha1, T. Sallemi-Boudawara1
1
Methods: A 42 year old female patient presented to the Ribeirão Preto Department of Pathology, Habib Bourguiba Hospital, Sfax, Tunisia
Clinics Hospital (HCFMRP-USP) Dermatology Outpatient Clinic with a
0,9 cm forearm pigmented nodule. It showed no ulceration or irregular Background & Objectives: Biphasic sarcomatoid carcinoma is an un-
pigmentation. Excisional biopsy was performed under the clinical hypothesis common biphasic neoplasm that has been reported in diverse anatomical
of pigmented basal cell carcinoma. The biopsy material was submitted for sites. The tumour is composed of a malignant epithelial component inti-
histopathological examination, fixed in buffered formalin, embedded in par- mately associated with a malignant mesenchymal component, which may
affin and routinely stained with hematoxylin-eosin. Immunohistochemical be homologous or heterologous. Only 47 cases of primary cutaneous
study was performed with antibodies targeted to CEA, Chromogranin, biphasic sarcomatoid basal cell carcinoma (BSBCC) have been reported
CK5/6, HMB45, MelanA, p63, S100 and Synaptophysin. in the English literature. We report a further one case of BSBCC of the
Results: Microscopically the lesion consists of a pigmented nodular scalp and include the clinical, histological and immunohistochemical
tumour of well-defined borders composed of biphasic celullar compo- features.
nents: (1) matrical cells that contain ovoid nuclei and frequent conspic- Methods: The histological and immunohistochemical features of
uous nucleoli, with an intermediate nuclear-cytoplasmic ratio; (2) BSBCC of the scalp are described with a review of the related literature.
dentritic melanocytic cells that are elongated and pigmented (Figure 1). Results: A 65-year-old man presented with an elevated and ulcerated
Clusters of ghost cells can be found dispersed through the lesion lesion on the scalp measured 20×15×6 mm. The lesion was surgically
(Figure 2). Cysts that contain hyaline proteinaceous fluid are sparse. excised. Histology showed basal cell carcinoma intimately admixed with
There is no necrosis or mitotic figures. The adjacent dermis show solar a sarcomatous component composed of spindle and oval atypical cells
elastosis and a mild dermal mononuclear inflammatory infiltrate. The with vesicular nuclei and quit high mitotic count. There was no heterol-
immunohistochemical profile of the neoplasm showed positivity to ogous stroma. Immunohistochemical analysis showed these cells to be
p63, with focal expression of high molecular weight cytokeratins positive for vimentin and negative for keratin and HMB45. The diagnosis
(CK5/6) of the epithelial matrical component (Figure 3). MelanA, of BSBCC was made. In our case, tumour was completely resected with
HMB45 and S100 stained positive in the dendritic melanocytes no recurrence or metastases.
(Figure 4). There was no reactivity of CEA, CK20, Chromogranin or Conclusion: The histogenesis of BSBCC has been extensively debated.
Synaptophysin antibodies. Four main theories have emerged, the most widely accepted was that the
Conclusion: Melanocytic matricoma is a very rare biphasic neoplasm com- sarcomatous component is a metaplastic transformation of the carcino-
posed of matrical cells admixed with dendritic melanocytes, with few case matous component which would confer an increase in aggressive poten-
reports and series of cases presented in current scientific literature. With the tial to the tumour. In view of this potential, complete resection is recom-
present case, we expect to contribute with useful clinical and pathological data mended.
to the current scientific knowledge of this rare entity.

E-PS-05-026
E-PS-05-023 Morphological and immunohistochemical studies of Kaposi sarcoma
Mycosis fungoides bullosa: a case report V. Filatov 1 , J. Omarova 1 , T. Bezuglova 2 , M. Mnikhovich 3 , A.
Î Yalçın1, A. Dobral1, S. Yıldırım2 Asaturova4, V. Kometova4
1
Istanbul Okmeydani Training and Research Hospital, Turkey, 2 Istanbul 1
Pirogov Russian National Research Medical University, Russia,
2
Maltepe University- Medical School, Turkey Research Institute of Human Morphology, Russia, 3 Research Institute
of Human Morphology (Moscow), Russia, 4 Federal State Budget
Background & Objectives: Mycosis fungoides is the most common Institution National Medical Research Center of Obstetrics,
type of cutaneous T-cell lymphoma which can be presented with different Gynaecology and Perinatology Ministry of Healthcare of the Russian
clinical and histological forms. Mycosis fungoides bullosa is a rare vari- Federation (Moscow), Russia
ant of mycosis fungoides. Therefore we report a case of mycosis
fungoides bullosa and review the relevant literature. Background & Objectives: The differential diagnosis of Kaposi sarco-
Methods: We present a case of mycosis fungoides in a 75-year-old man ma (KS) includes many tumours such as dermatofibroma, histiocytoid
who presented with erythematous plaques on all extremities histological- hemangioma, kaposiform hemangioendothelioma, angiosarcoma.
ly diagnosed as mycosis fungoides bullosa which is incompatible with the Methods: Biopsy material from 7 HIV negative patients (age 45-75
clinical apperance. years), 3 women (51, 32%) and 4 men (48, 68%), was studied. In 6 cases
Virchows Arch

(72,37%) patients complained of skin tumours. In 1 case (27,63%) diag- changed its color and size in the last week. Dermatology examination
nosis was established post mortem. revealed a 5x5 mm with skin lesion on the anterior face of the left thigh
Results: Immunohistochemical studies have shown monomorphic ex- with suspected signs on dermatoscope. Skin melanoma was suspected.
pression of CD34 by endothelial cells while expression of von elliptical incision of the lesion with narrow margins was performed.
Willebrand factor was heterogeneous, cells were generally negative for Results: We received a skin elips of 10x5x5 mm with a pigmented lesion
CD31. Endothelial cells and myofibroblast-like cells have shown focal of 5x5 mm. Microscopic examination showed a skin with a neoplastic
intensive nucleocytoplasmatic expression of HHV8. Myofibroblast-like proliferation of basaloid epithelial cells with mild atypia admixed with
cells demonstrated intensive Ki-67 positivity. Additional markers severely atypical large melanocytes colonized the epitelial component
(IgL(lambda), IgL(kappa), CD38, CD3, CD79a, CD30) were used. and showing lentiginous and inflitrative growth pattern. Melanocytic
Cells demonstrate intensive IgL(lambda), IgL(kappa), CD38 component showed positive stain for S100, Melana A and HMB45, while
cytoplasmatic expression, CD3, CD30 membrane and cytoplasmatic ex- epithelial component showed CK AE1-3 expresion. Cells with double
pression and membrane expression of CD79a. expression of S100 and CK were observed.
Conclusion: Pathomorphological diagnostics of KS should include his- Conclusion: The histogenesis of CCTs is not clear. 11q13 amplification
tological study with consideration of chaotic character of angiogenesis, in both components supports the theory of dual differentiation from a
proliferation of spindle cells with endothelial markers, mononuclear cell common progenitor cell. Studies showed that CCTs have better prognosis
infiltration, and immunohistochemical study with CD34, CD36, CD31, in comparison to melanomas with the same pathological stage.
Von Willebrand factor, and Ki-67. Additional markers (IgL(lambda),
IgL(kappa), CD38, CD3, CD79a, CD30) in pathomorphological practice
for differential diagnosis. E-PS-05-029
Sweet syndrome like neutrophilic dermatosis as an initial presenta-
tion of new-onset bullous systemic lupus erythematosus: a case report
E-PS-05-027 M. Zivanovic1, A. Vizjak1
1
Infundibulocystic basal cell carcinoma: an unusual variant at an Insitute of Pathology, Medical Faculty Ljubljana, University of
unusual age in sun protected skin Ljubljana, Slovenia
M. Mc Cabe1, J. Fitzgibbon1
1
Cork University Hospital, Ireland Background & Objectives: To report a case of bullous systemic lupus
erythematosus (SLE) that presented initially as a neutrophilic dermatosis
Background & Objectives: Infundibulocystic basal cell carcinoma (ND) in an adult male patient with antiphospholipid syndrome.
(BCC) is a rare variant with a distinct underlying mutation which contains Methods: 30-year-old male presented with annular erythematous skin
elements of follicular differentiation. <1% of BCC occurs in the vulva. eruptions on his trunk and thighs that clinically raised suspicion of urti-
Two previous cases of vulval infundibulocystic BCC have been described carial vasculitis. We examined the skin lesion from right thigh by light
in the literature. The first was a woman with widespread BCCs due to a microscopy and direct immunofluorescence, followed by indirect immu-
germline mutation in a gene downstream from Sonic Hedgehog. The nofluorescence (ELISA).
other was an elderly woman with concurrent Paget’s disease. Results: Histopathological examination revealed diffuse mild to moder-
Methods: We present the case of a 28-year-old woman who presented ate interstitial and perivascular dermal infiltrate composed predominantly
with a left upper labial cyst which, on histological examination, was of neutrophils, without accompanying fibrinoid necrosis of vascular walls
revealed to be an infundibulocystic BCC. The specimen was received or other histological features of presumed vasculitis. Direct immunoflu-
labelled as “Tiny left labial cyst.”. orescence showed so called »full house« deposition of IgA, IgG, IgM, C3
Results: Grossly, the specimen was a pale, round, smooth piece of tissue and C1q along dermo-epidermal junction, in vascular wall of small blood
measuring 6x4x3mm. The entire mass was embedded. At low magnifi- vessels and also along conective tissue fibers in dermis. These findings
cation, a well-circumscribed, palisading tumour was seen, consisting of were suggestive of SLE but also of possible hipocomplemented urticarial
infundibular-like structures with keratin plugs and anastomosing nests of vasculitis. Indirect immunofluorescence testing on blood sample was
basaloid cells, and tumour–stroma retraction. The tumour was superfi- negative for the presence of anti-C1q antibodies. Serological findings
cially located and at the margin. At higher magnification, the tumour cells were highly suggestive of SLE. Less than one month after the initial
had a high nuclear:cytoplasmic ratio with pleomorphism, hyperchromatic symptoms patient developed widespread vesiculobullous skin eruption.
nuclei, and inconspicuous nucleoli. Conclusion: While the association of ND and autoimmune connective
Conclusion: Infundibulocystic BCC is a less aggressive subtype whose tissue diseases is well recognized, Sweet syndrome like ND as a
underlying mutation differs from that found in more common forms. This presenting sign of SLE is reported only in a handful of cases,
case highlights the heterogeneity of BCC and in contrast with the previ- mostly in women. Even tough ND often presents in idiopathic
ous reports, occurred in isolation in a young woman. fashion, it is important to think about possibility of underlying SLE,
especially in younger patients.

E-PS-05-028
Combined cutaneous tumours with melanoma component. Case re- E-PS-05-031
port and literature review Cladophialophora Immunda: an extremely unusual infectious agent
A. Abuomar1 for chromoblastomycosis
1
Hospital General universitario de Elda, Alicante, Spain J.I. Franco1, A. Sobrino2, N. Torrecilla2, C. Yus2, P. Cerro3, R. Baldellou3,
C. López4, M.I. Millán-Lou4
1
Background & Objectives: Combined cutaneous tumours (CCTs) with Hospital Universitario Miguel Servet Zaragoza, Spain, 2 Anatomía
a melanoma component are very rare with only 49 cases in the literature Patológica. Hospital Universitario Miguel Servet, Spain,
3
up to our knowledge. Squamomelanocytic CCTs are the most frequent Dermatología. Hospital Universitario Miguel Servet, Spain,
4
followed by basomelanocytic CCTs and trichoblastomelanoma. We pres- Microbiología. Hospital Universitario Miguel Servet, Spain
ent a case of malignant basomelanocytic tumour and a literature review.
Methods: A 37 years old woman with brown eyes and skin phenotype Background & Objectives: Chromoblastomycosis, described for the
III, a medical history on hypothyroidism and frequent sunburns. Patient first time in 1911, with few cases reported in Spain, is a deep mycotic
arrived to our hospital complaining of that his year old left thigh nevi infectious disease, resulted from inoculation of dermatiaceous fungi
 Virchows Arch

after a traumatic injury, specially in males with a wide range of age. It E-PS-05-033
is a slow-course disease, predominantly reported in tropical or sub- Epidermodysplasia verruciformis: an unusual diagnosis
tropical areas. Clinically, it can simulate a malignant lesion, such as S. Yacoub1, S. Mistiri1, N. Abdessayed1, B. Sriha1, M. Mokni1, D. Chiba1
1
squamous cell carcinoma. It is a disease with an easy diagnosis that Department of Pathology Farhat Hached Hospital, Tunisia
needs microbiological correlation in order to stablish a specific
treatment. Background & Objectives: Epidermodysplasia verruciformis (EV)
Methods: We report the case of a 56-year-old male with history of kidney is a very rare genetic dermatologic condition, HPV related, caus-
transplant, with a fastly-growing verrucous lesion, asymptomatic, located ing an increased risk of cutaneous dysplasia and malignancy. The
on the right foot. An incisional biopsy was performed and a sample for lesions of EV tend to exhibit a characteristic histopathologic
microbiological culture was taken. appearance.
Results: Histological examination of the biopsy showed an ulcerative We describe a rare case of EV.
lesion, with pseudoepitheliomatous hyperplasia and superficial granulo- Methods: A 23 year-old female presented for management of a 3 cm
matous process, with multinucleated giant cells containing small, from 6 waxy-brown verrucous plaque on the forehead that appeared 1 year be-
to 12 μm, round dark-coloured structures, evidenced without any special fore. A biopsy of the lesion was performed.
stain. Subsequent microbiological culture allowed typify the microorgan- Results: The resected specimen was fragmented. Histopathologic
ism as Cladophialophora Immunda. examination of these lesions showed a thickened epidermis with a
Conclusion: Chromoblastomycosis,is a very uncommon disease in a verruciform architecture. The epidermis was aconthotic, covered
non-tropical country and Cladophialophora Immunda is an ex- by a marked orthokeratosis. Numerous koilocytic cellular atypia
tremely unfrequent microorganism among the dermatiaceous fun- was present associated to cluster of vacuolated cells with bubbly
gi, causal agents of this entity. The posibility of this diagnosis bluish cytoplasm. The superficial dermis showed a mild dermis
should be taken in consideration in a verrucous and ulcerated infiltrate.
lesion, from a tropical or subtropical climate country-native pa- Conclusion: EV is a premalignant entity, that needs a close dermatologic
tient, specially in situation of immunosupression. Microbiological monitoring.
cultures should be granted in order to typify the microorganism and stab-
lish the best treatment.
E-PS-05-034
Erithema Elevatum Diutinum - a rare and often misdiagnosed entity
E-PS-05-032 D. Vinha Pereira1, J. Ferreira1, A. Robson1 and J. Costa Rosa1
1
Epidermolytic ichthyosis: study of a family with skin fragility and Pathology Department, Instituto Português de Oncologia de Lisboa
palmoplantar keratoderma Francisco Gentil, Lisbon, Portugal
A. Sobrino Prados1, N. Torrecilla Idiope2, C. Yus Gotor2, P. Cerro2, Y.
Gilaberte2, J. Forteza2, J.I. Franco Rubio2, M.J. Viso Soriano1, S. Bakali Background & Objectives: Erythema (red) elevatum (elevated)
Badesa1, H.P. Almanzar Comas1, R.I. Bermudez Cameo1, N. Estrada diutinum (persistent) - EED is a rare middle-age chronic cutaneous
Mallarino1, î Arellano Álvarez1 vasculitis of unknown etiology associated with autoimmune, infec-
1
Hospital Universitario Miguel Servet Zaragoza, Spain, 2 Hospital tious and hematological diseases. Many clinical and histological
Universitario Miguel Servet, Spain mimics can be recognized, such as inflammatory conditions, in early
stages (e.g.: granuloma faciale, Sweet´s syndrome) or neoplasias, in
Background & Objectives: Epidermolytic ichthyosis (EI) is a rare au- later stages (e.g.: dermatofibroma, myxoinflammatory fibroblastic
tosomal dominant genodermatosis, affecting the keratinization and sarcoma).
suprabasal maduration of keratinocytes and is generally associated with Methods: We report two cases clinically diagnosed as a neoplasia (first
mutations in the keratin 1 and 10 genes. Symptoms in newborns are case) and epidermal cysts/keloid scars (second case).
bullous lesions, erythroderma and desquamation, followed by different Results: Two women (aged 42 and 50) with no relevant medical history
degrees of skin fragility in adulthood and sometimes, palmoplantar kera- presented with slowly developing multiple cutaneous limb nodules (first
toderma. Although in newborns there is an increased risk of infections or case) and facial papules (second case).
sepsis, the prognosis is usually good, but it depends also on the severity of Histologically, both cases revealed superficial and deep dermal mixed
each case. inflammatory infiltrates (more prominent on the second case), with abun-
Methods: One-month-old male presented bullous lesions in but- dant neutrophils and scattered eosinophils; neutrophilic vasculitis and
tocks, thighs and perioral area since birth. His mother, grandmother leucocytoclasis were present; fibrosis was particularly dense on the first
and uncle have a history of palmoplantar keratoderma along with case. Special stains for fungi and mycobacteria were negative. A diagno-
skin fragility with a tendency to suffer bullous and ulcerative lesions. sis of EED was performed (later and early stages, respectively).
Two biopsies, an ultraestructural and genetical study were necessary Although the first patient had a history of recurring limb nodules (outside
to reach the diagnosis. our institution), 15 months after this excision, she remains disease free.
Results: Newborn biopsies showed a subcorneal blister with eo- The second patient developed similar lesions at the same location after 6
sinophils and negative immunofluorescence. In the second biopsy years. There is no evidence of other systemic diseases in both cases.
of th e mother, a characteristic perinuclear cytoplasmic Conclusion: EED diagnosis is challenging and requires histological and
vacuolization of keratinocytes of higher strata was observed. clinical correlation, because of its strong association with systemic dis-
Ultraestructural study had images of epidermolysis of the eases. Isolated cases can also exist.
epidermocytes, being compatible with the EI. Massive sequencing
revealed a mutation in gen KRT1, p.Val198Glu; c.593>A, not de-
scribed before in literature, and usually associated with E-PS-05-035
palmoplantar keratoderma. A non-scalp neurocristic cutaneous hamartoma with malignant
Conclusion: transformation - a case report and review of literature
- EI is a rare genodermatosis with a broad clinical, histological and prog- C. Costa1, I. Gullo1,2,3, J. Pacheco1,2, J.M. Lopes1,2,3, E. Rios1,2,3
1
nostic spectrum, due to the different mutations in KRT1 and KRT10. Department of Pathology, Centro Hospitalar de São João, Porto,
- KRT1 alterations are associated with palmoplantar keratoderma. Portugal, 2 Department of Pathology, Faculty of Medicine of the
- Further research is needed to improve our knowledge of this entity. University of Porto (FMUP), Porto, Portugal, 3 Institute of Molecular
Virchows Arch

1
Pathology and Immunology at the University of Porto (Ipatimup), Clinic of Dermatovenereology Diseases, Clinical Center of Vojvodina,
Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal Novi Sad, Serbia, 2 Faculty of Medicine Novi Sad, University of Novi
Sad, Novi Sad, Serbia, 3 Pathology and Histology Center, Clinical Center
Background & Objectives: Neurocristic cutaneous hamartoma (NCH), of Vojvodina, Novi Sad, Serbia, 4 General Hospital 'Đorđe Joanović',
a rare hamartomatous-type lesion of neural crest origin, characteristically Zrenjanin, Serbia, 5 General Hospital 'Dr Radivoj Simonović' , Sombor,
unveils fibrogenic, melanocytic, and/or neuro-sustentacular differentia- Serbia
tion. NCH displays predilection for the scalp, and may be congenital or
sporadic. Despite few reported cases, up to 35% NCH (~40% congenital) Background & Objectives: Pretibial myxedema is a form of cutaneous
developed malignant transformation. Herein we report a sporadic NCH mucinosis. It is a rare, chronic dermatosis, caused by thyroid dysfunction.
with melanoma transformation and lymph node metastases. Methods: We present a 79-year-old female patient with chronic, symmet-
Methods: A 55-year-old-male with giant “bathing-trunk”-type pigmented ric, pretibial edematous, erythematous, yellowish plaques with affected
lesion since his adolescence, which displayed recent rapid growth. Resection skin resembling ‘peau d’orange’ followed by feeling of the weight in the
of two indurated subepidermal nodules was performed, then margins legs. The anamnestic data revealed the presence of thyroid dysfunction
widening/sentinel node/inguinal lymph node dissection. and diabetes mellitus, cholelithiasis and nephrolithiasis, as well as arterial
Results: Histology revealed a complex lesion comprising cellular blue nevus- hypertension and ischemic cardiomyopathy. In order to determine the
like and neurofibroma-like components, in a background of congenital intra- etiology of pretibial edema and accurate diagnosis, a skin biopsy was
dermal nevus. One of the nodules disclosed nodular melanoma area without done and histopathological findings confirmed the diagnosis of pretibial
ulceration of epidermis. Five out of eleven lymph nodes dissected (including myxedema.
sentinel node) disclosed metastases. Immunohistochemistry revealed common Results: The haematoxylin and eosin (H&E), Periodic Acid Schiff (PAS),
features of neurofibroma and melanocytic components. Diagnosis: NCH with Gomori and Giemsa staining were performed. Pathology analysis pre-
melanoma transformation. No BRAF mutations were detected. The patient sented a diffuse atrophic and distinctly hyperkeratotic epidermis with
was proposed for adjuvant chemotherapy/radiotherapy (recent case). flattened rete ridges. Dermis was expanded with granular appearance in
Conclusion: NCH is rare and can develop melanoma over variable time lower two thirds due to abundant deposits of mucin widely separating
course (15 to 67 years), due to etiopathogenesis that differ from low collagen bundles. Capillary blood vessels were dilated, while sweat
degree of cumulative sun damage skin melanomas. So far, 11 cases of glands were of regular shape and distribution.
malignant transformation (all as melanoma) NCH were reported (exclud- Conclusion: Our report confirms association between pretibial myxede-
ing the present case), 5 (~45%) of which developed metastases. ma and thyroid endocrinopathy. Histopathology is of crucial significance
in differentiating pretibial myxedema from other clinically similar condi-
tions such as stasis dermatitis. Due to prompt diagnosis and conduction of
E-PS-05-036 recommended therapy, the skin remission and good quality of life could
Quinquaud's decalvans folliculitis: a case report be accomplished.
S. Ben Khalifa1, N. Abdessaied1, S. Chaieb1, Z. Nfikha1, A. Ben
Abdelkader1, M. Mokni1
1
Pathology Department of Fattouma Bourguiba Hospital, Monastir, Tunisia E-PS-05-038
Merkel cell carcinoma, diagnostic experience in a reference hospital
Background & Objectives: Folliculitis decalvans (FD) of Quinquaud is a R. Lopez1,2, D.A. Suarez-Zamora1, L.E. Barrera-Herrera3, M. Rolon1
1
rare chronic follicular inflammatory process, extremely resistant to treatment, Department of pathology and laboratories, Hospital Universitario
causing follicular atrophy and subsequent hair loss. The etiology is still Fundación Santa Fe de Bogotá, Bogotá, Colombia, 2 School of
unknown. Medicine, Universidad de los Andes. Bogotá, Colombia, 3 Department
Methods: We report a case of FD diagnosed in the department of pathol- of Pathology and Laboratories, Hospital Universitario Fundación Santa
ogy of Farhat Hached hospital. Fe de Bogotá, Bogotá, Colombia
Results: A 31-year-old man presented to dermatology department
with a tumoural lesion on the scalp of 2 years duration, with Background & Objectives: Merkel Cell Carcinoma (MCC) is a poorly
progressive loss of hair. He had no medical history. Physical differentiated neuroendocrine tumour with very low frequency, usually is
examination revealed a nodular alopecic lesion of the scalp, 2cm located on the exposed skin and classically manifests with aggressive
in size. Bacteriological and mycological findings were negative. behavior and high recurrence and metastatic risk. We present the largest
Complete removal of the lesion was performed, and histopatho- series of MCC to date in Latin America focusing on understand and
logical examination revealed a FD of Quinquaud. clarify essential concepts for prompt diagnosis and management of this
Conclusion: FD is a chronic form of deep folliculitis that usually occurs not well known and aggressive disease.
on the scalp as oval patches of scarring alopecia at the expanding margins Methods: We present a cross-sectional descriptive retrospective study in
of which are follicular pustules. Any or all of the hairy areas of the body patients diagnosed with MCC at our University Hospital between
may be involved. The etiology is unknown, although Staphylococcus October 2003 and October 2018, we present the demographic, clinical
aureus is sometimes cultured from the lesions. Initially there is a follicu- and pathological variables of these patients.
litis; this is followed by disruption of the follicular wall and liberation of Results: 36 patients with histopathological diagnosis of MCC, 20
the contents of the follicle into the dermis. The dermis adjacent to the (55.6%) were men and 16 (44.4%) were women, male: female ratio of
destroyed follicle contains a mixed inflammatory cell infiltrate. Plasma 1.25: 1. The median age was 71.5 years and the age range was 17.0 to
cells are sometimes present in the infiltrate, particularly in resolving le- 87.0 years. 88.9% (32/36) of the patients were older than 50 years. The
sions. Foreign body giant cells may form around the hair shafts lying free most frequent location was facial skin (27.8%), followed by metastasis
in the dermis. FD sometimes responds to oral antibiotics but usually with unknown primary site (25.0%) and skin of the lower limbs and hip (
relapses after interruption of therapy, sometimes with severe scarring. 13.9%).
The incidence rate of Merkel cell carcinoma at our university hospital was
0.72 cases per 100 000 people between October 2003 and October 2018.
E-PS-05-037 Conclusion: This is the largest series of MCC to date in Latin America,
Pretibial myxedema- a case report we conducted a complete histopathological analysis, our information is
S. Jakovljević1,2, A. Fejsa Levakov3,2, L. Djurdjev4, V. Zečev5, L. consistent with what is referred to worldwide regarding the clinical and
Vujanović1,2, J. Sekulić4 histopathological characteristics.
 Virchows Arch

E-PS-05-039 Conclusion: Dermal CCS is a rare, highly malignant soft tissue tumour,
Malignant complex (composite) adnexal cutaneous tumour mistaken usually affecting young women and occuring most commonly in the
for basal cell cancer: a case report extremities. Due to its rapid and aggressive evolution, it should always
E. Delic1, J. Redzepagic2, D. Spirtovic1, T. Ramovic1, N. Bilalovic1 be considered in front of a fast-growing and rapidly ulcerating, cutaneous
1
Clinical Center University of Sarajevo/ Clinical Pathology and nodular lesion.
Cytology, Bosnia and Herzegovina, 2 Clinical Center University of
Sarajevo, Bosnia and Herzegovina
Sunday, 8 September 2019 – Wednesday, 11 September 2019
Background & Objectives: Adnexal tumours of the skin are rare, het- E-PS-06 | Digestive Diseases Pathology – GI
erogeneous group of tumours. Malignant tumours are even rarer than their
benign counterparts. Here, we describe a metastatic complex malignant
E-PS-06-001
adnexal tumour of the skin in the axillary lymph node.
Arylsulfatase B as prognostic marker in colorectal cancer
Methods: Case presentation.
Z. Kovacs1, L. Banias1, I. Jung1, S. Gurzu1
Results: A 46-year-old male patient is sent from another hospital in our 1
University of Medicine, Pharmacy, Sciences and Technology, Targu
institution due to an enlarged lymph node in the right axilla and multiple
Mures, Romania
masses in both lungs radiologically. Before this, the patient had the lesion
on the face skin, which was surgically removed 5 years ago, diagnosed as
Background & Objectives: Arylsulfatases are lysosomal enzymes with
basal cell cancer. Core needle biopsy of the lymph node is performed and
role in several metabolic processes. In normal colonic mucosa,
histological examination reveals microscopic picture suspicious for met-
Arylsulfatase B (ARSB) is present in the cell membranes. Few aspects
astatic skin cancer. The revision of the primary skin biopsy has been
are known about ARSB in colorectal adenocarcinoma (CRC). The aim of
obeyed and the diagnosis of the malignant complex adnexal tumour with
the paper was to evaluate the possible correlation between ARSB and
follicular, trichilemmal, sebaceous and ductal differentiation is
clincopathological aspects of CRC.
established. During the diagnosis process, the patient died.
Conclusion: Many histological subtypes of malignant adnexal tumours Methods: ARSB immunohistochemical expression (polyclonal, Abcam,
been described. These tumours are rare, locally aggressive, and have the dilution 1:50) was prospectively quantified in 45 CRCs. As membrane to
potential for nodal involvement and distant metastasis, with a pore clin- cytoplasmic translocation was seen in tumour cells, compared with nor-
ical outcome. Patients age under 50 requires a higher degree of suspicion mal mucosa, cases were divided into three groups, based on cytoplasmic
for the diagnosis of basal cell cancer. The complex histology of the pre- expression intensity and number of positive cells.
sented case emphasizes the importance of histopathological examination Results: ARSB was more expressed in young versus old patients
in the diagnosis and therapeutic management of malignant cutaneous (p=0.0095) and slightly higher in cases with ulcero-infiltrative aspect,
adnexal tumours. compared with polypoid tumours (p=0.0088). As regarding microscopic
aspect, the ARSB intensity increased with tumour dedifferentiation, all of
the G3/G4 cases showing high expression (p=0.041). It was also directly
E-PS-05-040 correlated with presence of lymph node metastasis (p=0.026) and lymph
Dermal clear cell sarcoma: a very rare and confusing diagnosis node ratio (14 cases out of 34 with a lymph node ratio <0.1 had low
A. Saidi1, R. Jouini2, F. Khanchel2, I. Hell2, W. Koubaa2, E. Ben Brahim2, ARSB expression, p=0.026).
A. Chedli-Debbiche2 Conclusion: In CRC, compared with normal mucosa, membrane to cy-
1
Pathology Department; Military Hospital for Instruction of Tunis, toplasmic translocation is characteristic. High ARSB intensity was corre-
Tunisia, 2 Pathology Department; Habib Thameur Hospital, Tunisia lated with increasing aggressiveness of CRC cancer, which underlines the
possible role of this enzyme as a prognostic maker of CRC.
Background & Objectives: Clear Cell Sarcoma (CCS) is a rare and
aggressive tumour with melanocytic differentiation. It was first This paper was supported by a Romanian Government-UEFISCDI Grant
described by Enzinger as a tumour that mainly involves the ten- nr. PCCF20/2018
dons and fasciae of the distal extremities of the young- to middle-
aged woman. It is characterised by the frequency of local recur-
rences and late metastases that explain its poor prognosis. Dermal E-PS-06-002
location is much rarer. AA Amyloidosis of the gastrointestinal tract associated with
We report a new case of dermal CCS and discuss its anatomoclinical Waldenström´s Macroglobulinemia
features M. Garcia Martos1, C. Perna Monroy2, C. Prada Puentes3
1
Methods: Standard Histological study of the tumour with immunohisto- University Hospital Gregorio Maraño, Spain, 2 Univ. Hosp. Ramon y
chemical analysis targeting the markers: Melan A, HMB45, P16, Cajal, Spain, 3 Univ Hosp Torrejon, Spain
Pancytokeratin, Ki67, PS100, CD68, Fact13a, EMA, Calponin,
Caldesmone. Background & Objectives: AL amyloidosis is a well-known complica-
Results: We report the case of a 65-year-old female patient consulting for tion of Waldenström´s macroglobulinemia (WM). AA amyloidosis is
a 1.5 cm large pedunculated tumour with a smooth surface arising commonly associated with chronic inflammatory disorders. We present
in the inner side of her right thigh. The mass has gradually in- a case of gastrointestinal AA amyloidosis and WM. We show the impor-
creased in size since 8 months. After excision, histological exam- tance of Congo red staining in bowel biopsies in patients with unex-
ination shows that the dermis is entirely occupied by an ill- plained gastrointestinal tract symptoms.
defined proliferation arranged in cellular bundles and clusters Methods: A 59-year-old male with WM and several months’ history of
surrounded by collagen bands. Tumour cells are spindle shaped or profuse diarrhea. He did not have fever, lymphadenopathy, or any other
epitheloid with often vesicular nuclei, otherwise hyperchromatic. The systemic manifestations, neither autoimmune nor connective tissue dis-
figures of mitosis are numerous. orders. The patient underwent a colonoscopy and multiple colonic
The tumour cells exhibit only a weak and focal positive PS100 staining biopsies.
with a proliferation index (Ki67) estimated at 5%. The diagnosis of der- Results: Biopsy specimens from colon and rectum showed marked eo-
mal clear cell sarcoma was additionally confirmed by Prof. Mentzel sinophilic acellular material in the lamina propia and submucosa, with
(Germany). variable inflammatory infiltrated. This material was Congo red positive
Virchows Arch

(showed apple-green birefringence under polarized light). Methods: A 63 year-old female was hospitalized with a mass in the
Immunohistochemistry showed strong positivity for AA deposits, con- rectosigmoid junction, liver metastases and an ovarian mass. The patient
firmed by immunoelectron microscopy. It was also detected high serum underwent surgery and the primary tumour and the ovarian mass were
monoclonal IgM levels. Disease progressed with renal, pulmonary, car- both sent to gross examination. The microscopic analysis was performed
diac, hepatic and bone marrow involvement. He began Rituximab therapy on paraffin-embedded tissue samples stained with hematoxylin-eosin.
but he had a lower digestive hemorrhagic episode and die. Immunohistochemistry was performed for the following markers: ki-67,
Conclusion: Amyloidosis is a well-known complication of IgG related CK7, CK20, Chromogranin A, Synaptophysin, CD56, CDX2.
gammapathy but it is rare in IgM related gammapathy, including WM, Results: Microscopy revealed a malignant population with 40% adeno-
and even rarer AA amyloidosis. Only a few cases have been reported of carcinoma differentiation and 50% neuroendocrine component. The neu-
AA amyloidosis associated with WM. This association is seen in 5% of roendocrine cells exhibited organoid and cribriform structures with ro-
all gammapathy cases. Since each subtypes of amyloidosis requires dif- settes-arrangements. Squamous differentiation was present. Surprisingly,
ferent therapy, amyloid subtyping is crucial. the examination of the ovarian mass revealed a serous cystadenofibroma
with malignant cells invading both the cystic wall and the normal ovarian
stroma. Immunohistochemistry showed positivity for CK20, CDX2,
E-PS-06-003 Chromogranin A and Synaptophysin and negativity for CK7. The prolif-
Clinical and morphological features of eosinophilic oesophagitis in eration rate was 70%. All these features were consistent with a MiNEN.
patients with asthma Conclusion: MiNEN is a rare entity and we highlight the importance of
L. Mikhaleva1, V. Golovanova1, V. Pechnikova1, O. Vasyukova1, E. the pathological exam considering both immunohistochemistry and clas-
Akopyan1, K. Midiber1, M. Gushchin1 sic stain examination. Based on its aggressive behavior we recommend an
1
Research Institute of Human Morphology, Russia optimal strategy of management and close supervision by a multidisci-
plinary team. Unexpected microscopical features and locations of metas-
Background & Objectives: Eosinophilic esophagitis (EoE) is an tases, as presented in this case, should always be considered as a possi-
immune-mediated condition, characterised by oesophageal dysfunction bility.
and eosinophil-predominant inflammation. Patients with EoE are more
likely to suffer from atopic conditions such as asthma than others. The
accepted threshold for eosinophil density for the EoE diagnosis is 15 eos/ E-PS-06-005
hpf. The research goal was to show EoE clinical and morphological Columnar-lined oesophagus less than 1 cm above gastro-oesophageal
features in patients with asthma. junction and Barrett's oesophagus: morphological features
Methods: We observed 81 patients, 46 of which had controlled asthma of L. Mikhaleva1, K. Voytkovskaya2, E. Fedorov2, A. Shidii-Zarkua3
1
different severity and the rest of them represented the comparison group. Research Institute of Human Morphology, Russia, 2 Moscow University
Moreover, 15 autopsy cases were used in this study. Imaging Hospital No. 31, Russia, 3 Pirogov Russian National Research Medical
(esophagogastroduodenoscopy), morphological (light microscopy), im- University, Russia
munohistochemical and morphometrical methods were used.
Additional EoE histological criteria are eosinophil microabscesses, basal Background & Objectives: Barrett’s oesophagus (BE) is well known
zone hyperplasia, dilated intercellular spaces, eosinophil surface layering, risk factor for oesophageal adenocarcinoma, though columnar-lined oe-
papillary elongation, and lamina propria fibrosis. sophagus (CLE) less than 1cm above gastro-oesophageal junction (GEJ)
Results: Morphometrical study showed mucosal layer atrophy. The ac- is not well characterised.
tive role of macrophages and NK-cells and an SE4+ and CB8+ cells The aim of our study was to perform a comparative morphological ana-
imbalance (SE4/SE8 <1) in the mucous membrane atrophy and sclerosis lyse of BE and CLE less than 1 cm above GEJ.
in the oesophagus and stomach were proven unlike the comparison Methods: We examined endoscopic biopsies of 60 patients: 23 with CLE
group. EoE infiltration evaluation revealed a significant number of mac- less than 1cm above GEJ and 37 with BE, stained with haematoxylin-
rophages and NK-cells which correlates with the subepithelial sclerosis eosin. Combined PASD/Alcian Blue stain was used for detection of gob-
prevalence, as well as earlier mucosa atrophy and lamina propria sclerosis let cells (GC). Each group of patients with GS was subdivided into groups
in the oesophagus than in the stomach and the duodenum. with single GS, low density GC (LDGC, count of GS <50%) and high
Conclusion: In conclusion, it is necessary to conduct a timely differential density GC (HDGC, count of GS >50%).
EoE diagnostics in patients with asthma, taking into account its frequency Results: In patients with CLE <1 cm above GEJ cardiac-type metaplasia
and EoE early development in these patients and its disabling complications. was found in 7 (30,43%), acid-producing metaplasia – in 4(17,39%) and
intestinal – in 12 cases (52,17%): SGC – in 4 (17,39%), LDGC – in 6
(26,09%) and HDGC – in 2 patients (8,7%).
E-PS-06-004 Cardiac-type metaplasia was found in 4 cases of BE (10,8%), acid-
A case of MiNEN arising in the rectum with metastases in a benign producing metaplasia – in 6 (16,22%) and intestinal metaplasia – in 27
tumour patients (72,97%): SGC in 8(21,62%), LDGC in 7(18,92%) and HDGC
I.A. Ungureanu1, A. Dumitru2, L.A. Ursache1, D.I. Enea1 in 12 patients (32,43%).
1
University Emergency Hospital Bucharest, Romania, 2 Department of Conclusion: Reactive changes of epithelium presented in 34,78% CLE
Pathology, "Carol Davila" University of Medicine and Pharmacy, cases and in 56,76% BE cases.
Bucharest, Romania The frequency of intestinal metaplasia was 1,4-folds higher and the fre-
quency of reactive changes was 1,6-folds higher in BE compared with
Background & Objectives: M i x e d n e u r o e n d o c r i n e - n o n - CLE less than 1 cm above GEL. Reactive changes were associated with
neuroendocrine neoplasms (MiNEN) are rare entities defined by presence and density of GC.
the presence of two morphologically different neoplastic compo-
nents (each at least 30% of the tumour), including a neuroendo-
crine one. High-grade MiNEN are usually aggressive neoplasms E-PS-06-006
with poor prognosis and the metastatic risk is correlated to the Invasive adenocarcinoma case in the background of intracholecystic
grade of the neuroendocrine component. In this paper we present tubulopapillary neoplasia originated from adenomyoma of
the first case of a high-grade MiNEN metastasized in an ovarian serous gallbladder
cystadenofibroma. T.C. Savli1, N. Dursun2, T. Bolme Savli3
 Virchows Arch

1
Istanbul Training and Research Hospital, Turkey, 2 University of Health E-PS-06-008
Sciences, Istanbul Health Practice and Research Hospital, Department of A case of gastrointestinal stromal tumour, mimicking signet ring cell
Pathology, Turkey, 3 Bagcilar Training and Research Hospital, Turkey carcinoma
A. Dobriakov 1 , K. Opalenov 1 , M. Antonov 1 , N. Shvets 1 , E.
Background & Objectives: The malignant potential of adenomyomas of Poputchikova1, V. Salaeva1, A. Tokmakov1, J. Cherkasova1
1
gallbladder has controversy. Neoplastic transformation potential in liter- City Clinical Hospital of the Bahrushin Brothers, Russia
ature is reported as 3%. Intracholecystic tubulopapillary neoplasms
(ICPN) are defined as preinvasive neoplasms, which form prominent Background & Objectives: Gastrointestinal stromal tumour (GIST)
protuding mass in gallbladder mucosa. There are no publications in the is the most common mesenchymal tumour originating in the di-
literature about intracholecystic tubulopapillary neoplasms originating gestive tract. Stomach is the most frequently affected anatomic
from adenomyoma. We present our case because it has adenomyoma site.
and intracholecystic tubulopapillary neoplasm and also invasive carcino- Methods: A 31-year-old female was admitted to the Emergency
ma foci in the same lesion. Department with weakness, vomiting blood, and emission of dark black
Methods: A 75-year-old male presented with abdominal pain. MRI re- stools. Her hemoglobin was 8.6 g/dl. Esophagogastroduodenoscopy
vealed 2.1x2.1cm sized lesion with heterogeneous contrast enhancement showed a submucosal tumour that protruded into the prepyloric antrum
containing suspected millimetric invasion areas at fundus of gallbladder. with a central ulcer.
On PET-CT scan there was intense FDG uptake in the same area, conse- Wedge resection of gastric tumour was performed. The histopathology of
quently cholecystectomy was performed. the gastric specimen showed a firm submucosal tumour measuring
Results: We encountered sized of 6.5x3x2cm polypoid lesion extending 4.5x3.5 cm in size, without margin involvement. Overlying mucosa
to lumen which was located at gallbladder fundus. Histopathological was focally ulcerated.
examination revealed a lesion within adenomyoma. This lesion protruded Results: Microscopically, the tumour was seen in the submucosa
from superficial mucosa with a pattern similar to ICPN. There were also and was composed of solid sheets of tumour cells with
millimetric invasive tumour foci which was confined to adenomyoma. hyperchromatic nucleus and clear cytoplasm. The periphery of
The tumour was extended to perimuscular connective tissue, as it was in t h e tu m o ur c o n t a i n e d a l i t t l e s p i n d l e ce l l c o m po n e n t .
the adenomyoma (pT2). After two year follow-up the patient had disease Morphology of tumour cells had a striking resemblance to gastric
free survival. adenocarcinoma with signet ring cell morphology. However, im-
Conclusion: ICPN arising in an adenomyoma with invasion is a rare munohistochemistry for epithelial markers (AE1/AE3, EMA,
condition. In addition, although there was pT2 invasion in the lesion; it CEA) were negative. DOG-1, CD34, CD117 were positive; and
was confined to adenomyoma; so the expected survival will be better than Ki67-index was 3%. The tumour was diagnosed as GIST in the
other pT2 tumours. As a matter of fact, our case has been living without very low-risk category.
disease for two year. Conclusion: We report the case of gastric GIST, mimicking gastric ade-
nocarcinoma with signet ring cell morphology.

E-PS-06-007
Mixed acinar endocrine carcinoma presenting as a polyp in stomach E-PS-06-009
T.C. Savli1, N. Dursun2, B. Yeni3, T. Bolme Savlı4 Distinguishing palisade veins as a histologic marker of oesophageal
1
Istanbul Training and Research Hospital, Turkey, 2 University of Health origin in endoscopically resected specimens
Sciences, Istanbul Health Practice and Research Hospital, Department of J. Aida1, K. Takubo1, T. Arai2, T. Ishiwata1
Pathology, Turkey, 3 University of Health Sciences, Department of 1
Tokyo Metropolitan Institute of Gerontology, Japan, 2 Tokyo
Pathology, Turkey, 4 Bagcilar Training and Research Hospital, Turkey Metropolitan Geriatric Hospital, Japan

Background & Objectives: Although, pancreatic neoplasms can occur Background & Objectives: Palisade veins (PV) are considered
in any of the sites where heterotopic pancreatic tissue is present, the markers of the oesophagogastric junction endoscopically. In cases
incidence of extra pancreatic pancreatic type neoplasms is very of endoscopic resection, the oesophageal or gastric origin of small
rare.Mixed acinar endocrine carcinoma (MAEC) is a rare clinical entity, cancers is determined solely on histologic information. In the previ-
with 30 or so cases of pancreas reported in the English literature. ous study, we revealed the PV corresponds to the intramucosal veins
Methods: The patient is a 58-year-old woman who presented with epi- with a minor axis exceeding 100 μm. In the present study, we mea-
gastric pain applied to another clinic. Endoscopic investigation was done sured the lengths of PVs to allow determination of tissue origin, in
and 5x4,5x3,7 cm measured polip at the region of corpus in the stomach various conditions such as cutting with longitudinal direction or ar-
was seen. Polipectomy was performed succesfully. tificial venal dilatation.
Results: This case was diagnosed as a well differantiated neuroendocrine Methods: We defined the intramucosal veins as reside in the
tumour, grade 3 and than consultated to our clinic. Microscopic exami- proprial mucosal lamina and also lying horizontally. We measured
nation showed a malignant neoplasm with morphologic features of mixed the lengths of intramucosal veins in H&E stained specimens in
acinar endocrine pancreatic tumour. Immumohistochemistry revealed dif- totally 30 ESD specimens from each 10 of the lower oesophagus,
fuse and strong positivity with trypsin, chromogranin A and upper or middle oesophagus, and gastric body not including the
synaptophisin that consistent with exocrine and endocrine differention. oesophagogastric junction.
There was no clinical or radiologic evidence of primary pancreatic tu- Results: The median lengths of intramucosal veins in the lower oesoph-
mour. After our diagnosis PET-CT scan was performed and there was no agus, upper or middle oesophagus and gastric body were 1880 μm,
metastatic lymph nodes or distant metastasis. 1074μm, and 848 μm, respectively. Those in the lower oesophagus were
Conclusion: Heterotopic pancreatic tissue in the stomach is relatively significantly longer than the others. The veins in the lower oesophagus
common when we compare with another heteropias.Mixed tumours of were significantly longer than the others, and oesophageal veins were
the pancreas are extremely rare and their clinical features and pathogen- significantly longer than those in the gastric body (maximum length in
esis remain unclear.Our case is originated from heterotopic pancreatic the latter, 902 μm).
tissue in the stomach and the first case in literature.If not carefully exam- Conclusion: In the lower oesophagus, intramucosal veins 100 μmwide or
ined, either the acinar or endocrine component may be overlooked and 1000 μmlong correspond to PVs. Histologically evident PVs can be used
misdiagnosed. as a marker of oesophageal origin.
Virchows Arch

E-PS-06-010 the proliferative index Ki67 can be used as prognostic marker for the
Adenosquamous carcinoma of gallbladder: a case report of an un- presence of metastases, disease progression and prognosis for neuroen-
common neoplasm docrine tumours.
I. Kourtesis1, A. Tsavari1, K. Koulia1, T. Vasilakaki1, G. Sotiropoulou2,
K. Manoloudaki1
1
Tzaneio General Hospital of Piraeus, Greece, 2 General Hospital of E-PS-06-012
Korinthos Greece Demographic characteristics, histological types and complications of
appendicitis operated in the clinical center of Vojvodina in 2015
Background & Objectives: Primary gallbladder adenosquamous carci- Z. Vrekic1, T. Lakic1,2, A. Ilic1,2, A. Lovrenski2,3, J. Amidzic1,2, J. Ilic
noma (GBASC) is an uncommon neoplasm, which accounts for 0,5%- Sabo1,2
1
12,7% of all malignancies (in the literature, it has been represented mostly Clinical Center of Vojvodina, Novi Sad, Center for Pathology and
as individual case reports). Females are affected most frequently, with a Histology, Serbia, 2 University of Novi Sad, Faculty of Medicine,
male to female ratio of 1:3. It has an aggressive behavior and a poorer Serbia, 3 Institute for Pulmonary Diseases of Vojvodina, Sremska
prognosis than adenocarcinoma. Here, we present a case of a male patient Kamenica, Serbia
with GBASC.
Methods: An 85-year-old male presented with pain in right hypochon- Background & Objectives: Appendicitis is one of the most com-
driac region. Ultrasound and CT-scan revealed an enlarged gallbladder mon surgical emmergencies of abdominal surgery. The treatment
with thickened wall and multiple calculi occluding the lumen. is routine procedure and includes removal of the appendix.
Cholecystectomy was performed. Macroscopically, it was an enlarged However, appendicitis is still interesting subject for research be-
gallbladder measuring 8x3x2cm, with a wall thickness of 0,7cm and a cause its etiology and pathogenesis remain unknown. The goal
firm tumour measuring 1,5cm in diameter in the region of the fundus. The was to determine incidence of the most common types of appen-
rest of the mucosa was of grayish tan color. dicitis, distribution by age and gender, incidence of periappendicitis as
Results: Microscopically, a superficially ulcerated malignant epithelial appendicitis associated pathology and to determine perforation
neoplasm was revealed, which comprised two main components: rate of the appendix.
a) a squamous moderately differentiated and mildly keratinizing carcino- Methods: The analysis is carried out using documents from the Center
ma which represented the majority (90%) of the tumour extent. The for Pathology and Histology of Clinical Center Vojvodina.
tumour invaded two thirds of the muscle wall thickness and was associ- Pathohistological samples were analysed with microscope and
ated with foci of squamous metaplasia, as well as squamous dysplasia. photographed. The results were processed in Microsoft office Excel and
b) a moderately differentiated intestinal type adenocarcinoma, focally displayed in tabular and graphical form.
invading half of the muscle wall thickness and growing on a background Results: A total of 626 cases of appendicitis from 2015 were analysed.
of high-grade biliary intraepithelial neoplasia (BilIN-3). Appendicitis affects patients from all age groups but more often occurs at
Conclusion: GBASC is a rare, aggressive malignant tumour. Reporting this a young age. It affects equally men and women. Acute forms of appen-
tumour adds to the literature and helps in better understanding the biological dicitis occur far more frequently than chronic. The results showed that a
nature and pathological characteristics of this uncommon entity. total of 306 patients had periapendicitis (48.88%). Perforation was pres-
ent in 2.72% patients.
Conclusion: Appendicitis is a disease predominantly of young
E-PS-06-011 population. The most common form of appendicitis is acute
Morphological and immunohistochemical features of neuroendo- phlegmonose appendicitis. Chronic appendicitis is more common
crine tumours in gastroenteropancreatic tract in elderly people. Perforation of the appendix is present in a very small
Z. Vrekic1, T. Lakic1,2, J. Ilic Sabo1,2, A. Ilic1,2, M. Panjkovic1, M. number of cases.
Zivojinov1,2
1
Clinical Center of Vojvodina, Novi Sad, Center for Pathology and
Histology, Serbia, 2 University of Novi Sad, Faculty of E-PS-06-013
Medicine, Serbia Coccidioides SPP in the cystic ganglion
M. Mejia1, J.D. Hernandez2, M. Rolon1, M. Baldión1, L.E. Barrera-
Background & Objectives: Neuroendocrine tumours (NETs) result from Herrera1, J. Alvarez-Figueroa1
1
neoplastic proliferation of neuroendocrine cells, with both characteristics Department of Pathology and Laboratory Medicine, Hospital
of endocrine and nerve cells. NETs can be different localizations but the Universitario Fundación Santa Fe de Bogotá, Bogotá, Colombia, 2
most common site is the gastrointestinal including pancreas. We evaluat- Department of Surgery, Hospital Universitario Fundación Santa Fe de
ed the morphology and frequency of NETs in our hospital as well as Bogotá, Bogotá, Colombia
correlation between lymph node status and Ki67 proliferative index.
Methods: Retrospectively, we analized NETs pathohistological reports of Background & Objectives: Coccidioides are soil-dwelling found in
patients who underwent surgical excision of gastroenteropancreatic tu- southern portions of California and southwestern United States,
mours in Clinical Center of Vojvodina in Novi Sad, in the period 2011- disseminated infection affects skin, skeletal system, and meninges.
2018. The descriptive and correlation statistics was done. Classic spherules measure up to 250 μm in diameter and contain
Results: It was registered 78 surgical specimens, average age of patients endospores (2-5 μm in size). Tissue response to Coccidioides is
58.88(±17),whereby 53.8% were male.The most frequent site was the granulomatous, with and without caseation, spherules are found in
pancreas (29.5%),followed by large intestine (26.9%).The mean tumour macrophages and multinucleated giant cells and classicaly
size was 3.71(±3.13)cm. Chromogranin A, Synaptophysin, CD56 and endospores.
Ki67 were usually used immunohistochemical markers.Lymph node me- Methods: A 45-year-old female with a recent trip to the United States
tastases were found in 47.44%.Positive correlation between the Ki67 presented to emergency service with 5-hour evolution of constant, burn-
index and the percentage of positive lymph nodes was determined (r = ing abdominal pain located in the epigastrium, 9/10 intensity and associ-
0.343, p = 0.046 p <0.05),so tumours with higher Ki67 index gave much ated with 1 soft stool, bilateral upper limb paresthesias, asthenia and
more lymph node deposits. adynamia. Bile duct ultrasound revealed nonspecific diffuse thickening
Conclusion: Most NETs lymph node metastases originated from high of the gallbladder walls, without evidence of stones inside.
grade tumours, with high Ki67 index. All mentioned above suggest that Cholecystectomy was performed.
 Virchows Arch

Results: The gallbladder presented changes due to acute and identified in the ampulla of Vater. The tumour was 7x3,8x2,5cm in
chronic cholecystitis with cholesterolosis. Cystic ganglion exposed diameter.
the presence of round micotic microorganisms with presence of Results: The histological examination revealed that the tumour consisted
spherules containing endospores inside, positive with PAS, nega- of two components. One was an adenocarcinoma, exhibiting tubulary and
tive for gomory and mucicarmine. Coccidioides infection was cribriform architecture while the other was a sarcoma containing atypical
recognized. mesenchymal cells. Immunohistochemically, the sarcomatous atypical
Conclusion: Intraabdominal coccidioidomycosis is a very rare entity, to cells were diffusely positive for vimentin, S100 and focally positive for
our knowledge, this is the first described cystic ganglion compromise due α-smooth muscle actin; these cells are also negative for pancytokeratin
Coccidioides. and desmin. It did not contain heterologous elements. The tumour was
therefore diagnosed as a carcinosarcoma. There was four lymph node
metastasis.
E-PS-06-014 Conclusion: Carcinosarcoma of the ampulla of Vater has a poor progno-
Correlation of E-Cadherin with pathological features in colorectal sis, and lymph node metastases are often seen. We have presented an
cancer extremely rare case of carcinosarcoma of the ampulla of Vater.
I. Msakni1, R. Hedhli2, N. Mansouri1, F. Gargouri1, A. Saidi1, A.
Bouziani1, B. Laabidi2,3
1
Pathology Department; Military Hospital for Instruction of Tunis, E-PS-06-016
Tunisia, 2 Tunis El Manar University, Medicine School of Tunis Cecal mucinous adenocarcinoma with heterotopic ossification: a case
Military Hospital of Tunis, Department of Pathology, Tunisia, 3 report and review of the literature
Military Hospital of Tunis, Department of Pathology, Tunisia A. Podrimaj-Bytyqi1, M. Hashani1,2
1
Faculty of Medicine, University of Pristina, Albania, 2 Institute of
Background & Objectives: An important mechanism of Colorectal Pathology, University Clinical Center of Kosovo, Albania
cancer progression is the Epithelial-mesenchymal transition. It is
responsible for promoting the migratory phenotype of cancer Background & Objectives: Heterotopic ossification is a very rare event
cells through inhibition of adhesion molecules and stimulation in the gastrointestinal tract tumours, being less than 0.4% among them.
of mesenchymal markers. The main marker is the loss of mem- The mechanism of ossification is still unclear. It’s usually observed in
brane E-cadherin expression. Many studies showed that colorectal tumours associated with mucine extravasation, subsequent calcification
cancer with low E-cadherin expression tend to have poor of which it is thought to be a predisposing factor. Furthermore, osteoblas-
prognosis. tic metaplasia of cancer cells and pluripotent mesenchymal cells, both
Our objectives were to analyse the expression of E-cadherin in under the influence of factors generated by the cancer cells, are proposed
colorectal cancer and its correlation with histopathological as possible mechanisms.
parameters. Methods: We present a case of a 25 years old male, who was admitted to
Methods: It was a retrospective and monocentric study of 68 patients surgical clinic with acute intestinal obstruction due to the presence of a
with colorectal cancer, collected at the Department of Pathology between cecal mass. The computed tomography scan and ultrasonography showed
2011 and 2014. an irregular cecal mass with signs of calcification or ossification. Patient
Results: The median age of the patients was 62 years (27-87 years). 74% underwent surgery, where a right hemicolectomy with regional lymphad-
of patients were males with a sex ratio of 2.9. Immunohistochemical enectomy was undertaken.
study showed 38 E-cadherin positive and 30 E-cadherin negative tu- Results: Macroscopically, tumour was located on the upper part of the
mours. The expression of E-cadherin was inversely proportional to the cecum, near the ileo-cecal valve, it perforated the wall and caused cecal
degree of differentiation (p = 0.001). There was no statistically signifi- ischemic necrosis due to the total obstruction. Tumour was exophytic,
cant correlation between the expression of E-cadherin and other histo- 5 cm in diameter, with hard/osseal consistency. Histologically, well dif-
pathologic parameters. ferentiated mucinous adenocarcinoma with heterotopic ossification was
Conclusion: the expression of E-cadherin protein in colorectal cancer is diagnosed. In the resected specimen, six negative lymph nodes were
correlated with histopathological parameters like in our study. found. Immunohistochemistry for Ki67 showed a low index of prolifer-
Identification of regulators of gene expression involved in the ation; CK20 and CEA were positive, while CK7 and p53 were negative.
Epithelial-mesenchymal transition process is critical for understanding Conclusion: Heterotopic bone formation in colon is a rare phenomenon,
tumourigenic mechanisms and therefore facilitate the development of especially in young patients. Colon cancer and other benign lesions of the
novel therapies. colon which are presented with heterotopic ossification, needs to be dif-
ferentiated from carcinosarcoma, which has a similar clinical presenta-
tion, but worse prognosis.
E-PS-06-015
Carcinosarcoma of the ampulla of Vater: a case report
S. Batur1, C. Turker1, Z.E. Kain1, N. Kepil1 E-PS-06-017
1
Istanbul University Cerrahpasa-Cerrahpasa Medical Faculty A rare soft tissue tumour of the stomach
Department of Pathology, Turkey I. Dumitru1, M.A. Bani1, X. Sastre Garau1, T. Lons1
1
CHI Crèteil, France
Background & Objectives: Carcinosarcomas are rare malignant tu-
mours that are composed of both carcinomatous and sarcomatous ele- Background & Objectives: Glomus tumour is a rare benign menchymal
ments that grow intermingled with each other. This tumour type has been neoplasm derived from the glomus body witch is an arteriovenous anas-
detected in many different organs. However, carcinosarcoma of the am- tomosis. The stomach is an exceptional site for those tumour. Their diag-
pulla of Vater is extremely rare. nosis may pose a real challenge for the pathologist especially in small
Methods: The patient was a 47 year-old woman, She complained of gastric biopsies.
discomfort in the upper abdomen. Abdominal magnetic resonance imag- Methods: A 56 –year-old man with no history referred for a microcytic
ing indicated nodular lesion at the head of pancreas and anemia. The endoscopy revealed an ulcerated lesion of the greater curva-
pancreaticoduodenectomy with lymph node dissection were performed. ture of 34 mm. The diagnostic of a stromal tumour was presumed and a
Macroscopically, the well-demarcated, polypoid, infiltrative tumour was biopsy performed. Histologically the tumour was composed of uniform
Virchows Arch

round cells with regular nuclei and pale eosinophilic cytoplasm. Background & Objectives: The use of Operative Link on Gastritis
Immunohistochemistry expression for smooth muscle actine and absence Assessment (OLGA) and Operative Link on Gastritis Assessment based
of staining for S100 proteine and CD117. The retained diagnosis was on Intestinal Metaplasia (OLGIM) staging system is recommended to
gastric glomus tumour. identify subjects at risk for developing gastric cancer, generally high-
Results: Glomus tumours are rare. The first case of gastric glomus tu- risk lesions are considered only stages III and IV. Accumulating evidence
mour was reported in 1951, since then only 34 cases have been reported is suggesting that incomplete IM is of importance in developing gastric
in the literature. The tumour is generally benign however in one case cancer.
metastasis have been reported. Malignant behaviour may be associated Our aim was to identify the prevalence of incomplete IM in
with the size, localization, high nuclear grade and atypia. The diagnosis patients with low-risk OLGA/OLGIM stages in a high-risk gener-
can be challanging with endoscopic and radiologic findings witch are al population.
nonspecific for such tumours. Immunohistochemistry is mandatory to Methods: Healthy adult volunteers aged 40-64 years were invited to
rule out other differential diagnoses. undergo upper endoscopy within a regional GISTAR pilot study in
Conclusion: We think that the diagnosis of a glomic tumour on a biopsy Kazakhstan (n=166). Five gastric biopsies according to the updated
is challanging. It raises a large spectrum of differential diagnoses. The Sydney system were obtained from each study subject. High iron
pathological asses may pose the diagnosis but their prognostic factors are diamine-alcian blue (HID-AB) was used for the subtyping of IM.
still to be proven. Results: Overall 46.0% IM prevalence was revealed. Incomplete IM was
present in 48.0% (type II in 22.0% and type III in 26.0%), whereas
complete IM was found in 52.0% of individuals. The prevalence of
E-PS-06-019 OLGIM I and II stage was 85.0% and 10.0%, respectively, whereas
CD44 expression in dysplastic glands of colorectal adenomas OLGIM III was observed in 5.0%. The prevalence of incomplete IM in
G. Cerrone1, V. Aimola1, G. Senes1, R. Murru1, G. Faa1,2 patients with OLGIM I was 32.0% (type II in 18.0% and type III in
1
Division of Pathology, Department of Medical Science, University 14.0%).
Hospital San Giovanni di Dio, AOU Cagliari, University of Cagliari, Conclusion: High prevalence of incomplete IM was revealed not only in
Cagliari, Italy, 2 Temple University, Philadelphia, Pennsylvania, USA subjects with extensive IM, but also in those stratified OLGIM I stage.
Without IM subtyping, up to 32.0% of the patients with high risk of
Background & Objectives: CD44 is an ubiquitous transmembrane gly- gastric cancer development would be missed for surveillance.
coprotein that interacts with different components of the extracellular
matrix. Different isoforms of CD44 exist since the mRNA encoding for
this protein may undergo alternative splicing. CD44 isoforms have been E-PS-06-022
related to multiple cancers, being considered stem cell markers of many Gastric glomus tumour: a case report
tumours. Z.E. Kain1, S. Batur1, N. Kepil1, O. Aydın1, N. Comunoglu1
1
CDX-2 is a fundamental regulator of intestinal development and onco- Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine,
genesis, which is considered a prognostic biomarker. Pathology Department, Turkey
In this study we evaluated CD44 and CDX-2 immunohistochemical ex-
pression in polyps and adenomas of the colorectum. Background & Objectives: Glomus tumour (GT) is a rare mesenchymal
Methods: We evaluated 7 cases of polyps/adenomas of the colorectum. tumour of stomach,arising from glomus bodies.Peripheral soft tis-
At histology 2 adenomas with high grade dysplasia (A/HGD), 4 adeno- sues and extremities are the major sites of involvement. Case
mas with low grade dysplasia (A/LGD) and 1 sessile serrated polyp series revealed that GT is 100 times rarer than gastric GIST. It
without dysplasia (SSPwD) were identified. Immunohistochemical eval- is known as benign, and wedge resection with tumour-free margin is
uation for CDX-2 and CD44 was performed. adequate for treatment. Since first case reported in 1951, there are less
Results: All cases analysed showed diffuse and intense nuclear immuno- than 100 case reports in English literature up-to-date. Clinically and his-
reactivity for CDX-2. All adenomas showed membrane strong and dif- topathologically, differential diagnosis includes gastric GIST,
fuse immunostaining for CD44, except for one A/LGD that revealed a leiomyomas and neuroendocrine tumours.
focal immunoreactivity. CD44 immunostaining was mainly localized in Methods: A 60-year-old female was admitted to the hospital with a pain
dysplastic glands. Areas with high grade dysplasia showed stronger reac- in the left upper abdomen. A computed tomography (CT) scan of the
tivity for CD44 than those with low grade dysplasia. Only SSPwD abdomen demonstrated well-defined lesion, measuring 24x22 mm in
showed no evidence of CD44 expression. close relation to the anterior wall of the stomach. The patient underwent
Conclusion: Our preliminary data show that the stem cell marker laparoscopic wedge resection of the gastric mass with a preliminary di-
CD44 is expressed in colorectal adenomas. The reactivity for CD44 agnosis of gastrointestinal stromal tumour. Surgical resection revealed a
is stronger in high grade than in low grade dysplasia. Further studies 2x1,5x1cm well circumscribed submucosal tumour, extending into the
are needed to better clarify the role of CD44 expression in colon subseroza.
carcinogenesis. Results: Microscopically,the tumour showed submucosal infiltration by
solid sheets of round cells having a nodular pattern of growth,separated
by fibrous bands. The neoplastic cells were uniform with round
E-PS-06-021 nucleus,clear to eosinophilic cytoplasm,and a distinct cell border
The value of subtyping of intestinal metaplasia for the risk stratifica- separated by dilated vascular channel lined with flat endothelium.
tion of gastric cancer There were no mitosis,cytomorphological atypia or necrosis. The
S. Savcenko1, S. Isajevs2,3, I. Bogdanova1,3, I. Liepniece-Karele1,3, M.B. proliferative index (Ki-67) was 1%. Immunohistochemically, the
Piazuelo4, M. Leja1,3 tumour cells were stained positive for alpha-smooth muscle actin, beta
1
Institute of Clinical and Preventive Medicine; Faculty of Medicine, catenin, vimentin, collagen type IV and synaptophysin. The tumour cells
University of Latvia, Riga, LV-1586, Latvia, 2 Department of were negative for CD117, CD34, pancytokeratin,HMB-45,S-100,CD56
Pathology, University of Latvia, Faculty of Medicine, Riga, and chromogranin.
Latvia, 3 Centre of Pathology, Riga East University Hospital, Conclusion: GT is a rare entity that clinicians and pathologists may not
Riga, Latvia, Latvia, 4 Division of Gastroenterology, Department come across in their lifelong career. It can be easily misdiagnosed as
of Medicine, Vanderbilt University School of Medicine, Nashville, neuroendocrine tumour and may cause pitfalls. Recent imaging tech-
Tennessee, 37232, USA niques or endoscopic biopsy are not reliable differentiating from other
 Virchows Arch

mesenchymal tumours. We have presented an extremely rare case of GT Necrosis and inflammatory elements as well as foci of abscess formation
of the stomach. were also noted.
Conclusion: The colon and particularly the cecum, is a highly uncom-
mon site of RCC metastatic involvement. In general, this atypical presen-
E-PS-06-023 tation occurs many years after the initial kidney resection, although in our
Leishmaniasis of duodenum: a case report patient this occurred only a few months after the initial resection.
G. Sotiropoulou1, O. Abazis1, C. Vasileiou1, E. Axioti1
1
General Hospital of Korinthos, Greece
E-PS-06-025
Background & Objectives: Leishmaniasis is a disease caused by an Nosologic structure of gastric pathology in cases of endoscopic mu-
intracellular protozoan parasite (genus Leishmania) transmitted by the cosal resections
bite of female phlebotomine sandfly (genus Phlebotomus). The disease M. Shushval1, L. Volkova2,3, G. Lyashenko4, L. Nyzhnik4, A. Antishina2,
is divided into 3 clinical forms: cutaneous,mucocutaneous and visceral. A. Musatov2, K. Abdujabborov1
1
Visceral leishmaniasis (kala-azar) is a potentially lethal widespread sys- Baltic Federal University, Russia, 2 Immanuel Kant Baltic Federal
temic disease characterised by fever, weight loss, hepatosplenomegaly, University, Kalinigrad, Russia, 3 Lab. of Immunohistochemistry and
darkening of the skin, pancytopenia and hypergammaglobulinemia.The Pathology Diagnostics, Russia, 4 Regional Hospital, Pathoanatomical,
prognosis is poor without special treatment(70%-90%).In Greece are re- Kaliningrad, Russia
corded 30-70 cases of visceral and about 10 cases of cutaneous leishman-
iasis annually. Background & Objectives: Gastrointestinal endoscopic mucosal resec-
Methods: A 32 year old foreign male shepherd presented in the outpa- tion (EMR) is one of methods of diagnostics and treatment of exophytic
tient department with anemia. The patient also reported malaise, weak- epithelial lesions of the stomach. Our study is aimed to evaluate nosolog-
ness and anorexia. CBC count demonstrated microcytic hypochromic ical structure and morphological peculiarities in EMR stomach
anemia, leukopenia with decreased neutrophils and relative lymphocyto- specimens.
sis. Prothrombin time was prolonged and biochemical studies were within Methods: The study was performed on 62 stomach samples of patients of
normal range. US showed splenomegaly. An upper GI endoscopy was Kaliningrad Regional Hospital after EMR during 2016-2018.
perfomed - with no essential findings - and biopsies were taken from the Characteristics of the study group with epithelial lesions of the stomach:
stomach and duodenum for the investigation of anemia. sex (M:F) - 10:52, age: 36-75 years.
Results: Histological examination showed a dense lymphoplasmatic Results: Pathologic process location in the stomach: 1) body - 69.2%; 2)
population with participation of neutrophil granulocytes, as well as plenty pylorus - 12.5%; 3) antrum - 12.1%; 4) cardia - 7.1 %. 49 cases of
of macrophages, which in their cytoplasm contained the baseophilic hyperplastic polyps with following histological appearances were re-
Leishman Donovan bodies. The amastigotes were confirmed by vealed: 1) low grade intraepithelial neoplasia – 2; 2) intestinal metaplasia
Giemsa stain. of the colonic type - 1; 3) inflammation - 6; 4) ulceration - 9; 5) cystic
Conclusion: Leishmaniasis cases are increasing in numbers favored by glandular hyperplasia – 3. Tubulovillous adenomas (9) were found: 1) 7
changing immigration conditions. The disease should be included in the cases – with low grade intraepithelial neoplastic changes; 2) 2 specimens -
differential diagnoses of various infectious parasitic disorders . with high grade intraepithelial lesions. Diagnosis in 1 patient - Menetrier's
Serological studies and PCR are less invasive methods for the detection disease. 3 cases of malignancy were observed: 1) high grade adenocarci-
of the disease.Early diagnosis , treatment and informing the population noma in hyperplastic polyp - 1; 2) high grade adenocarcinoma in
are the main measures for controlling leishmaniasis. tubulovillous adenoma - 2.
Conclusion: The predominance of benign pathology of the stomach
among EMR samples was demonstrated (79.0%), but in some patients
E-PS-06-024 the intraepithelial neoplastic changes (14.5%) and superficial adenocar-
A unique renal cell carcinoma solitary colonic metastasis. An atypical cinomas (4.8%) were found. Diagnosis of epithelial lesions of the stom-
metastatic presentation ach in EMR specimens is necessary for early diagnostics and effective
E. Koniaris1, I. Nikolopoulos1, E. Gioti1, K. Tsiardis1, E. Moula1, G. treatment of benign processes and early stages of malignancy.
Kafiri1
1
"Hippokratio" General Hospital of Athens, Greece
E-PS-06-026
Background & Objectives: Our aim was to present a rare and atypical Ossified gastric tumour with tumour trombus - case report
metastastasis of a renal cell carcinoma(RCC), eosinophilic type, to the I. Guvendir1, K. Altundag1, I. Tosun2, I.E. Zemheri1, K. Ozdil3
1
cecum. RCCs are tumours with strong prevalence to metastasize, virtually Health Sciences Health Sciences University Umraniye Eduation and
to all organs, but most frequently to lung, bone, brain and liver, with a 30- Training Hospital Pathology Department, Turkey, 2 Umraniye Training
40% recurrence, after resection and a 10% risk of metastasis after 5 years. and Research Hospital, Department of Pathology, Turkey, 3 Health
The gastrointestinal tract and especially the colon is a very unusual site. Sciences Health Sciences University Umraniye Eduation and Training
Methods: Our patient referred to our hospital for a regular check up, 6 Hospital Gastroenterology Department, Turkey
months after a total nephrectomy for a RCC , a tumour mass was found
endoscopically on the cecum. He underwent right colectomy and we Background & Objectives: Glomus tumours of the stomach are very
received cecum of 20cm in length, with a protruding, ulcerated tumour rare, mesenchymal neoplasms, account for nearly 1% of all gastrointesti-
m.d.: 7cm, 6cm from the ileocecal valve. Due to the previous history nal soft tissue tumours. The most common involvement of stomach is
immunohistochemistry was performed with the following: AE1/AE3 antrum. Gastric glomus tumours are submucosal tumours that lack spe-
(+), CK7 (+), CK20(-), S100 (-), LCA (-), Chromogranin (-), cific clinical and endoscopic characteristics and are often mistaken for
Synaptophysin (-), HMB45 (-), Alcian blue (-), PAS (-). gastrointestinal stromal tumours.
Results: Histologically, the tumour was a high grade carcinoma, with Methods: A 62-year-old female presented with upper gastro-intestinal
mainly solid growth pattern, with tumour islands with delicated fibrovas- bleeding for 15 years. Endoscopic ultrasound revealed a 3.5x2.7 cm-
cular cores between them. The tumour cells had high nuclear atypia and sized, round, hyperechoic mass with a central ulcer and focal calsification
pleomorphism, with presence of bizarre cells with multilobular and mul- at the gastric wall. Endoscopic ultrasound-guided fine-needle aspiration
tinucleated forms, high mitotic index and bright eosinophilic cytoplasm. (EUS-FNA) was applied.
Virchows Arch

Results: Cytologic examination revealed a losely cohesive, uniform, The aim of our study is to evaluate DC numbers in CRC patients tested
small, round to oval cells with scant cytoplasm, indistinct cell borders for MSI/MSS and to assess their significance for association with MSI
and hyperchromatic nuclei with homogeneous chromatin. After that, lo- and with patients’ survival.
cal resection was performed. Macroscopically, 4.5x3x1.5 cm nodular Results: MSI patients have statistically significantly greater number of
mass arising submucosa and muscular layer was observed. Microscopic CD1a+ DCs in tumour stroma (TS) (p=0.001) and in the invasive front
and immunohistochemical findings were consistent with a gastric glomus (IF) (p=0.002). In patients with stage II CRC CD1a+ DCs in TS (p=0.001)
tumour with ossification and vascular tumour trombus. Mitosis was and in IF (p=0.021) are statistically significant increased number. The
1/50Hpf. After the diagnosis, the patient underwent systemic examina- same dependence is observed for CD83+DCs. CRC MSI patients having
tion, metastasis was not found despite vascular tumour trombus. There increased number of CD1a+DCs both in TS (p=0.028) and IF (p=0.045)
was no evidence of recurrence 6 months after the resection. show a tendency for longer survival as compared to those with lower
Conclusion: Gastric glomus tumour is very rare and ossified glomus numbers of CD1a DCs in MSS patients. There was a tendency for longer
have not been yet reported in English literature. We reported this case survival of patients having increased number of CD11c+ DCs in TS
because of rarity and distinctive features. (p=0.106).
Conclusion: CD1a+ DCs number and CD83+ DCs number are associated
Key words Stomach, Glomus tumour; ossification, Endosonography; with MSI status of CRC patients. They could be used as predictive im-
Biopsy, fine-needle; Cytology munohistochemical marker for MSI.

This work was financially supported by the National Science Fund,

E-PS-06-027 Bulgaria, Research grant number KП-06-H23/2 from 17.12.2018.
Precancerous and background processes in carcinomas of the stomach
M. Shushval 1 , L. Volkova 2,3 , A. Antishina 2 , L. Nyzhnik 4 , K.
Abdujabborov1 E-PS-06-029
1
Baltic Federal University, Russia, 2 Immanuel Kant Baltic Federal Appendiceal intussusception secondary to benign lymphoid hyper-
University, Kalinigrad, Russia, 3 Lab. of Immunohistochemistry and plasia in appendix and cecum: report of two cases
Pathology Diagnostics, Russia, 4 Regional Hospital, Pathoanatomical, M.E. Kara1, E. Uzun1
1
Kaliningrad, Russia Gaziantep University Medical Faculty Hospital, Department of
Pathology, Turkey
Background & Objectives: Revealing of precancerous and background
processes for gastric carcinomas is very important for prophylaxis and Background & Objectives: Benign lymphoid hyperplasia in the wall of
early diagnostics. The aim of the study investigation of pathological pro- intestines is usually located in the terminal ileum and it occurs in children
cesses associated with various types of gastric carcinomas. and young adults. Intussusception is a common cause of acute abdomen
Methods: The study group - 29 patients with arcinomas of the stomach in infancy. Here we present two appendiceal intussusception cases devel-
after gastrectomy, sex (M:F) - 19:10, age: 42-75 years. Specimens from oped due to benign lymphoid hyperplasia.
the tumours and at the different distance were investigated for evaluation Methods: Case 1: An 11-month-old baby girl was presented with discom-
of morphological peculiarities of the background and precancerous pro- fort, vomiting, abdominal pain and blood in feces. Abdominal ultrasonog-
cesses in the mucosa. raphy (USG) examination revealed the appendiceal intussusception. During
Results: Location of gastric cancer (cases): 1) body – 14; 2) cardia – 8; 3) the operation intussusception was detected, appendix and cecum wall were
antrum – 4; 4) pylorus – 1. The main cancer type - adenocarcinoma ( 23 found thickened. Right hemicolectomy was performed. Microscopically;
cases) of different Grade: G3 - 11; G1 - 10; G2 – 2. Precancerous and there was extensive benign lymphoid hyperplasia both appendix and cecum
background processes in the subgroup of adenocarcinomas: 1) chronic wall. It has been verified with immunohistochemistry.
gastritis of different activity - weak (8), moderate (7), severe (5); 2) intes- Results: Case 2: A 10-month-old baby boy referred to our hospital with
tinal metaplasia (17); 3) epithelial hyperplasia (13); 4) low grade (9) and vomiting, abdominal pain, and blood in feces. In abdominal USG,
high grade (3) dysplasia; 5) glandular atrophy (6). Precancerous and appendiceal intussusception was detected. The patient was treated surgi-
background processes in the subgroup of diffuse cancer (total -5): 1) cally. Intraoperatively, the appendix was wide and cecum wall was thick-
chronic gastritis (5) of different activity - weak (0), moderate (4), severe ened. In additionally; small lymph nodes and thinned wall cyst were
(1); 2) intestinal metaplasia (2); 3) epithelial hyperplasia (2); 5) glandular found in the mesenterium. Histological examination revealed benign lym-
atrophy (3). Mucinous adenocarcinoma (1) was revealed with association phoid hyperplasia in appendix and cecum. The diagnosis was supported
with severe active chronic gastritis and intestinal metaplasia. by immunohistochemically.
Conclusion: It was revealed that the main background pathology in gas- Appendiceal intussusception is a very rare entity which has been
tric carcinomas of different types is chronic gastritis, the most common many pathological conditions such as fecalith, foreign body, para-
precancerous processes - intestinal metaplasia and dysplasia. sites, and rarely benign lymphoid hyperplasia. In the gastrointestinal
tract, lymphoid hyperplasia leads to confusion, while it is induced
by allergy, parasites, immunological diseases or no cause is detect-
E-PS-06-028 ed. In infancy, appendiceal intussusception secondary to lymphoid
CD1a+ DCs and CD83+ DCs number is associated with MSI status of hyperplasia is rare. The diagnosis is difficult preoperatively, histo-
CRC patients logical examination is necessary.
M. Gulubova1, K. Ivanova1, T. Vlaykova2
1
Trakia University, Medical Faculty, Department of General and Clinical
Pathology, Bulgaria, 2 Trakia University, Medical Faculty, Department E-PS-06-030
Chemistry and Biochemistry, Bulgaria Case report of a signet ring cell carcinoma of the ampulla of Vater
A. Dimitriadi1, C. Karambogias1, G. Koutsonikas2, C. Zorzos1, A.
Background & Objectives: About 15% of colorectal cancers (CRC) display Kostopoulou1, A. Koliopanos3, T. Choreftaki1
1
a deficiency in the DNA mismatch repair (MMR) system. MSI CRCs are Department of Surgical Pathology/General Hospital of Athens "G.
associated with intense by lymphocyte infiltrate. Dendritic cell (DC) infiltra- Gennimatas", Greece, 2 Department of Cytology/General Hospital of
tion in CRC is investigated in CRC patients. The tumour tissue contains most Athens, "G. Gennimatas", Greece,3 2nd Department of Surgery/General
S100+ and CD1a+ DCs and very few numbers of all other CD types. Hospital of Athens "G.Gennimatas", Greece
 Virchows Arch

Background & Objectives: We present a case of signet ring cell carci- Y. Ozerdem1, B. Koca1, S. Kulacoglu1
1
noma (SRCC) of the ampulla of Vater of a 68 year old man, submitted for Ankara Numune Training and Research Hospital Department of
obstructive jaundice. Pathology, Turkey
Methods: Endoscopic Retrograde Cholangiopancreatography (ERCP)
highlighted oedematus and brittle ampulla of Vater with constriction at Background & Objectives: The histological, clinical and prognostic
the lower end of common bile duct. Biopsy was performed, positive for a aspects of the neoplastic gallbladder polyps were not well-described his-
primary poorly differentiated adenocarcinoma. A Whipple procedure was torically. ICPN terminology is defined recently, for mass forming
performed. We received a pancreatoduodenectomy. exophytic gallbladder lesions distinct from adjacent mucosa, measuring
Results: A tumour was located at the ampulla of Vater with maximum ≥1 cm and showing dysplasia. ICPNs are seen predominantly in women
diameter 1.5cm. Microscopically, the tumour consisted of, mostly, diffusely and mean age is 61.
arranged, poorly differentiated cells, with signet ring cell morphology, infil- Methods: A 65-year old male with abdominal pain underwent an abdo-
trating the duodenal wall, with lymphatic invasion and without infiltration of men CT which revealed a heterogenous nodular mass in the gallbladder.
adjacent pancreas or peripancreatic soft tissue. Fourteen lymph nodes were Grossly a 1.4x1x1 cm green, pedinculated, friable polypoid lesion was
identified with no metastases (pT2N0M0, according to AJCC 8th ed.). seen at gallbladder corpus.
Immunohistochemical staining showed that the tumour cells were posi- Results: Microscopic sections showed a papillary neoplasm composed of
tive for CK19, CK7, MUC1, MUC5AC, and focally for CK20, MUC2, tightly packed glandular epithelium with foci of tubulary configuration. The
TTF1, MUC6 and negative for SYP, CgA and b-catenin. Thus, the diag- morphologic appearance of the glands were variable consisting of biliary
nosis was a mixed type SRCC with intestinal, pancreatobiliary and gastric epithelium, clear cells with broad cytoplasm and hyperchromatic epithelium
differentiation. accompanying intestinal metaplasia. High grade dysplasia is observed at %30
Conclusion: Ampullary SRCC is an extremely rare neoplasm with only of the glands. Immunohistochemical staining showed the predominant cell
38 cases described so far, from which only 3 were mixed type. Some type to be pancreatobiliary with diffuse and strong MUC1 and CK7 staining.
studies indicate that mixed type SRCC, especially with gastric differenti- The gastric foveolar type glands showed MUC5AC staining and the foci of
ation, has worse prognosis. Furthermore, coexpression of E-cadherin and intestinal differentiation were CK20 and CDX2 positive. Apart from the
b-catenin may show poorer prognosis. lesion, high grade dysplasia was also consistent in the fundus, corpus and
neck extensively, with cytoplasmic pCEA staining.
Conclusion: ICPNs are rare neoplasms with remarkable cell lineage di-
E-PS-06-031 versity and biliary pattern is the most common. Although gallbladder
Histologic description of cytopathic effects of Human Herpes Virus 6 carcinomas arise mainly from flat dysplasia, extensive evaluation is es-
(HHV6) enteritis sential to exclude invasion. Reporting histopathological, immunohisto-
S. Renne1, C. De Carlo1, T. Brambilla1, M. Sollai1, J. Mariotti1, E.C. chemical and clinical aspects of polypoid preinvasive gallbladder neo-
Ferrara1, L. Di Tomaso2,3, M. Roncalli2,3, P. Spaggiari1 plasms will contribute to our knowledge about ICPNs.
1
Humanitas Clinical and Research Center - IRCCS, Italy, 2 Department
of Pathology, Humanitas Clinical and Research Center - IRCCS, Rozzano
(MI), Italy, 3 Department of Biomedical Sciences, Humanitas University, E-PS-06-033
Rozzano (MI), Italy Gastric adenosquamous carcinoma: A case report
S. Batur1, R. Akpinar1, N. Kepil1
1
Background & Objectives: Patients undergoing bone marrow transplan- Istanbul University Cerrahpasa-Cerrahpasa Medical Faculty
tation (BMT) often require gastrointestinal (GI) biopsies to rule out viral Department of Pathology, Turkey
infections or Graft Versus Host Disease (GVHD). HHV6 is a very prev-
alent infection affecting 95% of the general population, and it remains Background & Objectives: Adenosquamous carcinoma, a rare ma-
latent in most of the cases, but it represents a common pathogen in im- lignant tumour of the stomach, is characterised by two different
munocompromised hosts. However, a histological description of its cy- cell components, one adenomatous and the other squamous com-
topathic effect in GI tract is missing. We here provide the first histologic ponent. It amounts to less than one percent of all gastric carcino-
description of HHV6 enteritis. mas and its clinical and endoscopic findings are similar to the
Methods: A 53 years-old man with a 31 years-long history of Hodgkin’s adenocarcinoma. It occurs more frequently in the proximal stomach and
lymphoma and previous reactivation of HHV6 infection, underwent to BMT. tends to be found in advanced stages at diagnosis, with a worse prognosis
He developed grade 3 mucositis, sepsis, diarrhea, nausea and vomiting. GI than adenocarcinoma.
biopsies were performed to rule out GVHD: duodenum showed cytopathic Methods: A 56-year-old male was admitted to the hospital with a pain in
alterations suggestive of viral infection; cytomegalovirus infection was ex- the left upper abdomen. An upper gastrointestinal endoscopy had re-
cluded, and polymerase chain reaction analysis revealed the presence of vealed an extensive ulcer of the gastric antrum. The patient underwent a
HHV6 DNA. Lower-GI biopsies showed atrophy and apoptosis, compatible distal subtotal gastrectomy. Grossly specimen revealed an
with GVHD. The patient was thus treated with Ganciclovir and ulceroinfiltrative lesion occupying most of the antrum, measuring
Methylprednisolone-Etanercept. Four months later, the patient developed a 8×5×3cm, and infiltrating his gastric wall to the serosal layer. On cutting
severe anemia and a lethal Aspergillus pneumonia. the liver fragment, a tumour was identified as a whitish nodular subcap-
Results: Duodenal biopsy showed atrophy and mild subacute inflamma- sular lesion of well-defined limits with a major diameter of 0.5cm.
tion of lamina propria; few apoptotic enterocytes were identified; epithe- Results: A pathological exam revealed a poorly-differentiated malignant
lial and stromal cells showed marked cytomegaly and nuclear inclusions. epithelial neoplasia of solid pattern and focally glandular with
Conclusion: To our knowledge this is the first histological description of expansive growth. Venous, lymphatic and perineural invasion
cytopathic effects of HHV6 enteritis. Histology is of paramount impor- were identified. There was metastatic neoplasia in four of the
tance in the management of patients undergoing BMT. HHV6 should be ten identified lymphatic nodes, as well as in her liver fragment.
considered in presence of cytopathic effects and CMV negativity. Immunohistochemically, the tumour cells were stained positive for
CK7, CK5-6 and p40. The tumour cells were negative for CK20,
synaptophysin and chromogranin. The tumour was diagnosed as
E-PS-06-032 adenosquamous carcinoma.
Intracholecystic papillary-tubular neoplasm (ICPN) with high grade Conclusion: Primary gastric adenosquamous carcinoma is a rare malig-
dysplasia: a case report nancy. Its clinicopathologic feature and prognosis are quite different from
Virchows Arch

the ordinary adenocarcinomas. We have presented an extremely rare case Conclusion: Spindle cell lipoma is a rare lipomatous tumour and to our
of adenosquamous carcinoma of the stomach. knowledge has never before been reported in the appendix. The behav-
iour of spindle cell lipomas arising at unusual sites is not well known and
therefore, for treatment purposes, they should be considered as similar to
E-PS-06-034 that of atypical lipomatous tumour.
Carcinoid tumour and Cystoisospora belli infection of the gallblad-
der: a case report
B. Koca1, Y. Ozerdem1, S. Kulacoglu1 E-PS-06-036
1
Ankara Numune Training and Research Hospital Department of Rapid detection of mismatch repair proteins by immunohistochem-
Pathology, Turkey istry in colorectal cancer patients
K. Kubelka-Sabit1,2, V. Filipovski1,2, B. Dimova1, D. Jasar1
1
Background & Objectives: Carcinoid tumour of the gallbladder is a Clinical Hospital Acibadem Sistina, Department of Histopathology and
rare entity comprising less than 1% of all carcinoid tumours. Cytology, Republic of North Macedonia, 2 Medical faculty, University
Cystoisospora belli, formerly known as Isospora belli is an intra- Goce Delchev, Republic of North Macedonia
cellular parasite which is mostly associated with gastrointestinal
disease in immunocompromised patients. Gallbladder Background & Objectives: Lynch syndrome is an inherited disorder that
cystoisosporiasis in immunocompetent individuals is also increases the risk of many types of cancer, particularly colorectal and
described. endometrial cancer. Therefore, all newly diagnosed colorectal cancers
Methods: A 84 year old woman was hospitalized with nausea and ab- should be screened for Lynch syndrome. New immunohistochemistry
dominal pain in the right upper quadrant. She had no remarkable prior (IHC) based tests which detect mismatch repair (MMR) proteins offer
history. Abdominal ultrasound showed multiple gallstones with signs of quick and reliable identification of patients with probable Lynch
cholecystitis and cholecystectomy was performed. 0,4 cm polypoid mass syndrome.
was found in the neck of the gallbladder at gross examination. Methods: In this prospective study, we evaluated 50 cases of colorectal
Results: Histological examination revealed that the polypoid tumour was cancer patients using the Ventana MMR IHC Panel. The panel contains
composed of small uniform cell nests with round to oval nuclei invading five primary mouse or rabbit monoclonal antibodies: MLH-1 (M1),
the mucosa extensively, and penetrating the superficial muscular layer in PMS2 (EPR3947), MSH2 (G219-1129), MSH6 (44) and BRAF V600E
a small focus. No mitoses, lymphovascular and perineural invasion were (VE1). The analysis was performed on automated platform Ventana
seen. Tumour cells showed positive reaction for chromogranin and Bench Mark GX, using 4μ thin tissue sections from representative tu-
synaptophysin. This lesion was proved to be neuroendocrine tumour mour tissue paraffin blocks.
grade 1 (carcinoid) of the gallbladder. There was also an area in corpus Results: Of the 50 analysed cases, 3 cases showed absence of positivity
with eosinophilic intraepithelial parasites consistent with C. belli. for MLH1 and PMS2 markers. Two of these cases had MLH1 promoter
Intestinal metaplasia and follicular cholecystitis were also seen. hypermethylation and were classified as sporadic cancers. One case was
Conclusion: Carcinoid tumour and cystoisosporiasis of the gallbladder negative for PMS2 marker and one case was negative for MSH6 marker.
are extremely rare entities. Most of the cases are incidental. To our knowl- In total, 3 of the 50 cases analysed were sent for further Lynch syndrome
edge this is the first case report of a patient with carcinoid tumour accom- testing. Two of these three patients were female and also had a history of
panying C. belli infection. Although being relatively uncommon, these endometrial cancer prior to the diagnosis of colorectal cancer. One case
two entities should be considered in the differential diagnosis of gallblad- was positive for BRAF V600E antibody.
der diseases. Conclusion: Immunohistochemical detection of MMR proteins enables
quick detection of patient with probable Lynch syndrome. Further iden-
tification of the syndrome in patients and family members may result in
E-PS-06-035 early detection and possible cancer prevention in these patients.
Spindle cell lipoma of the appendix: a rare incidental finding
R. Griffiths1, A. Arnaout1
1
St. George's University Hospitals NHS Foundation Trust, United E-PS-06-037
Kingdom Primary extra-ampullary duodenal adenocarcinoma: a rare case
report
Background & Objectives: Spindle cell lipoma is a benign form of H. Seneldir1, G. Kir1, E. Apaydin Arikan1, T. Soylemez1, O. Ekinci2
1
lipoma typically found in soft tissues. They show a male predom- Istanbul Medeniyet University, Department of Pathology, Turkey,
2
inance and the majority are diagnosed between 45 to 65 years of Istanbul Medeniyet University General Surgery Department, Turkey
age. Most have a characteristic distribution with up to 80% of
cases arising on the posterior neck, shoulders, and back. Less Background & Objectives: Tumours arising in the non-ampullary seg-
frequently lesions arise intradermally or in the head and neck ment of the duodenum are rare and considered true duodenal cancers.
region, including in the oral cavity, face and orbit. Individual case These malignant neoplasms, accounting for 0.5% of all gastrointestinal
reports have documented occurrences in the mediastinum, labium malignancies and 33–52% of small bowel adenocarcinomas.
majus and perineum. Methods: A 87-year-old male patient was admitted to our general surgery
Methods: We present a case of an 84 year old female with weight loss clinic with complaints of abdominal pain, nausea and vomiting. Upper
and anaemia. She underwent an extended right hemicolectomy for an gastrointestinal endoscopy was performed for diagnostic purposes. In the
adenocarcinoma detected on CT scan. Macroscopically an incidental endoscopic imaging, a submucosal mass was observed between the 3rd
8mm firm white nodule was identified at the tip of the appendix. and 4th segment of the duodenum causing ulceration in the mucosa. Two
Results: Histological examination showed a spindle cell tumour repetitive endoscopic biopsies showed regenerative changes in the duo-
consisting of mature adipose tissue merging with spindle cells displaying denum. As the patient's complaints persisted, duodenectomy was
pale eosinophilic cytoplasm and uniform wavy nuclei. The spindle cells performed.
showed strong and diffuse positivity for CD34 and were negative for Results: Macroscopically, a 2 cm diameter tumoural lesion was found in
CD117 and DOG1. S100 highlighted mature adipocytes but was negative the submucosa of the duodenum. The mucosa in this area was regular in
in the spindle cells. Histological features confirmed a spindle cell lipoma appearance. Histologic examination revealed that the submucosal lesion
of the appendix. was a well- moderately differentiated adenocarcinoma with clear cells.
 Virchows Arch

The tumour invaded the mucosa, muscularis propria and serosal fatty finding. They are usually located on the surface of the liver and are
tissue. No dysplasia was found in the surrounding tissue. <1 cm in diameter. These rare lesions should be included in the differen-
Immunohistochemistry was diffusely positive for Cam5.2, MUC-6, tial diagnosis of hepatic masses in addition to metastatic tumours if the
MUC 5AC, MUC 1, DPC4, CEA-P, negative for CK7, CK20, CDX2, patient has another malignancy.
MUC2, NKX2, PAX8, PSAP, SALL4, TTF-1, NAPSİN A, HMB45, Methods: A 70 year old woman with a diagnosis of colorectal adenocar-
TFE-3. Secondary involvement was excluded by extensive immunohis- cinoma was undergoing surgery when a small nodule was discovered on
tochemical panel and PET screening. the surface of the left lobe of her liver. Thought to be possible metastatic
Conclusion: Extra-ampullary duodenal adenocarcinomas are divided in- disease this lesion was excited and sent for pathologic evaluation. The
to two major subsets, intestinal type and gastric type, are associated with diagnosis of this nodule was benign in frozen sections intraoperatively
distinct histopathologic features and clinical behavior. Our case was eval- and colectomy was performed during the same operation.
uated as extra-ampullary duodenal adenocarcinoma originating from Results: Macroscopically the nodule of the liver was well circumscribed
Brunner glands or gastric heterotopia. but not encapsulated, gray-white nodule measuring 1 cm in diameter. The
microscopic study of the lesion showed an increased number of small,
normal appearing bile ducts lined with a single layer of cuboidal cells
E-PS-06-038 which were positive to cytokeratin 7, negative to cytokeratin 20 and had a
CD4+ and CD8+ lymphocytes in the immune microenvironment of ki67 proliferation index of 1%. The morphology, immunophenotype and
gastric cancer: evaluation in Tumour Tissue (TT) and Adjacent ki67 proliferation rate were consistent with a bile duct adenoma. The
Areas of Unchanged Mucosa (AAUM) tumour of the colon was a pTNM stage II adenocarcinoma.
I. Mikhailov1, N. Danilova1, P. Malkov1, N. Oleynikova1 Conclusion: Recognition of this unusual co-existence of tumours could
1
Lomonosov Moscow State University, Russia help to elaborate the appropriate therapeutic strategy for these patients.

Background & Objectives: The assessment of tumour immune microen-

vironment in AAUM isn’t enough studied. This is an important direction in E-PS-06-040
gastric cancer research because immune cells in AAUM may contribute in A rare case of acute abdomen in a pregnant woman – deciduosis of
epithelial-mesenchymal transition and tumour metastasis. CD4+ and CD8+ the appendix
lymphocytes are the main component of antitumour immunity which controls F. Galante Pereira1, A. M. G. Pereira1, C. A. Padrão1, J. Palla Garcia1, R.
all other cellular reactions. It is known that high density of intratumour CD4+ S. S. Oliveira1
1
and CD8+ infiltration is associated with better prognosis in gastric cancer Hospital Prof. Doutor Fernando Fonseca, EPE, Portugal
patients but it is not well known in AAUM.
Methods: 55 cases of gastric cancer (surgical material) were included in Background & Objectives: Ectopic decidua reaction or deciduosis is a
our study. Lymphocytes identification was performed by immunohisto- physiological phenomenon that results from the effects of progesterone
chemical staining on markers CD4 (clone 4B12) and CD8 (clone C8/ on extrauterine mesenchymal cells during pregnancy. In rare cases, ec-
144B). Cell counting was performed in three fields of view (magn. topic decidual tissues can develop in the appendix. This case report pre-
x200) separately in TT and AAUM. These results were compared with tends to raise the awareness of this uncommon finding.
classic tumour characteristics: depth of invasion (T), number of nodes Methods: A 30-year-old primigravida in her 17st week of an uncomplicat-
metastases (N), distant metastases (M), grade (G). ed pregnancy, presented with nausea, right lower abdominal pain, positive
Results: CD4+ infiltration in TT (median=37,8 cells) was higher than in Blumberg sign, slightly increased inflammatory markers, and a positive
AAUM (median=19,5 cells) in samples with N3 tumours (p=0,6148); ultrasound for acute appendicitis. Following the diagnosis of appendicitis,
CD4+ infiltration in AAUM in samples with N3 tumours was significantly the patient was later submitted to an appendicectomy. Hematoxylin-eosin,
higher than in samples with N2 tumours (median=11,33). CD8+ infiltration vimentin, calretinin and AE1/AE3 stain were performed.
in TT (median=105,79 cells) was higher than in AAUM (median=72,21 Results: On specimen handling, there were white plaques and small
cells) in samples with T4a tumours (p=0,7123); CD8+ infiltration in nodules on the serosa. Histologically, the lesion was composed by hap-
AAUM (median=74,33 cells) in samples with T4a/T4b tumours was sig- hazardly distributed sub-mesothelial decidualized cells, occasionally
nificantly higher than in samples with T1a/T1b tumours (median=48,33). forming nodules. The vimentin was positive and the vimentin, calretinin
Conclusion: High density of CD4+ and CD8+ infiltration in AAUM in and AE1/AE3 stain were negative.
gastric cancer is associated with greater depth of invasion and large number Conclusion: It is important to be aware of less frequent causes of acute
of lymph modes metastases which is opposite to intratumour infiltration. This abdomen in a pregnant woman. All these diseases can present with sim-
indirectly confirms the hypothesis that CD4+ and CD8+ in AAUM may be ilar clinical and imagiologic findings, highlighting the role of the pathol-
involved in tissue restructuring that conduct to the tumour progression. ogist in the final diagnosis.

E-PS-06-039 E-PS-06-041
Coexistence of intrahepatic bile duct adenoma and colorectal Evaluation of reproducibility of the diagnosis of gastric
adenocarcinoma intraepithelial neoplasia/dysplasia: possibility of using mathod as a
D. Anestakis1, C. Tsompanidou2, P. Konstantinidou1, M.I. Givannakis3, I. part of continuous professional education for pathology
Fountos4, P. Pavlidis5 S. Mozgovoi1, A. Kononov1, A. Shimanskaya1, M. Parygina1, M.
1
Department of Autopsy Histopathology, Lab. of Forensic Medicine and Keruchenko1
Toxicology, Aristotle University of Thessaloniki, Greece, 2 Department 1
Omsk State Medical University, Russia
of Pathology, General Hospital of Thessaloniki "Agios Dimitrios" ,
Greece, 3 Surgical Department, General Hospital "AHEPA", Background & Objectives: There is a need to introduce optimally re-
Thessaloniki Greece, 4 Forensic Service of West Republic of North producible classification approaches into the practical activity through the
Macedonia, Kozani, Greece, 5 Lab. of Forensic Medicine, Medical system of continuous education. The purpose of this study was to assess
School, Democritus University of Thrace, Greece the level of consistency of the pathology diagnosis of gastric
intraepithelial neoplasia / dysplasia on the consensus model.
Background & Objectives: Bile duct adenomas are benign prolifera- Methods: A collection of 45 histological slides from the material of
tions of intrahepatic bile ducts usually encountered as an incidental gastrobiopsy was compiled. All diagnostic categories of the Modified
Virchows Arch

Vienna classification of gastrointestinal neoplasia were showed on these Background & Objectives: Hepatoid adenocarcinoma (HA) is a rare
data. Histological slades were stained with hematoxylin and eosin and and highly aggressive tumour, firstly described in the stomach, morpho-
then were photographed to obtain 216 representative images.Only the logically characterised by hepatocellular and adenomatous differentia-
unambiguously evaluated cases were included (26 cases corresponding tion. HA can occur in other organs including the colon, where less than
to 98 images). An analysis of the agreeement of the diagnostic evaluation 20 cases have been reported.
was performed by peer review using the Cohen's kappa. Methods: We present the case of a 49-year-old female patient taken into
Results: The kappa level ranged from 0.2 (poor agreement, unweighted medical care for rectal bleeding. The colonoscopy revealed a sigmoid
kappa) to 0.47 (average level of agreement, linear weighted) and 0.66 tumour for which biopsies confirmed a poorly differentiated adenocarci-
(good agreement, quadratic weighted ). A simplified assessment method noma. A CT scan excluded any distant lesion and the patient underwent
was used to record individual expert opinion in the binary evaluation sigmoidectomy with lymph node resection.
format in regard to neoplasia/dysplasia diagnosis (yes/no). The applica- Results: Pathological examination revealed cuboidal atypical cells with
tion of this approach led to 0.47 unweighted kappa, which corresponds to eosinophilic cytoplasm, arranged in a solid or trabecular fashion, resem-
average level of agreement. bling that of HA. The tumour cells were positive for hepatocellular markers
Conclusion: The analysis showed average degree of agreement. The (alpha-fetoprotein, HepPar-1, Glypican 3 and Arginase) and also for gastro-
difficulties of introducing modern definitions of intraepithelial intestinal origin marker (CDX-2). The tumour was finally staged pT3N1b
neoplasia/dysplasia such as a large number of diagnostic categories, an (2 positive lymph nodes, including the pedicular lymph node) with a mis-
insufficient level of agreement in evaluating the signs of intraepithelial match repair proficient status. The patient was treated with a cytotoxic
neoplasia/dysplasia, the lack of full follow-up to recommendations were regimen of FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil) during 3
identified. months, with stable results being achieved after 5 months.
Conclusion: The HA is a rare type of primary colon cancer, that carries a
very poor prognosis. It is essential to exclude a primary hepatocellular
E-PS-06-043 carcinoma. Because little is known about the pathogenesis of this unusual
Cystic lymphangioma of the sigmoid colon: a case report tumour, further studies are needed to identify a potentially guided
A. Jurescu1, A. Dema1,2, S. Tăban1,2, M. Cornianu1,2, A. Mureșan1,2, C. standardised management.
Lăzureanu1,2, R. Cornea1,2
1
Department of Pathology, "Victor Babeș" University of Medicine and
Pharmacy, Timișoara, Romania, 2 Department of Pathology, Emergency E-PS-06-045
County Hospital Timișoara, Romania Analysis of gastrointestinal (GI) tract pathology frozen sections (FS)
in tertiary referral cancer hospital in India: an audit of 3 years (1/1/
Background & Objectives: Lymphangiomas are considered benign 2016 to 31/12/2018)
malformations of the lymphatic system but still, their pathogenesis is K. Deodhar1, A. Jadhav2, R. Kumar2, M. Bal2, M. Ramadwar2
1
poorly understood. They are occasionally found in the abdomen, being European Society of Pathology, International Academy of
generally cystic in type in this area. Colon cystic lymphangiomas are Pathology-Indian Division, India, 2 Department of Pathology,
infrequently, the sigmoid segment being the least common location. At Tata Memorial Hospital, Mumbai, Homi Bhabha National
the same time, they are very rare in adulthood only a few cases being University, India
reported in the elderly. They usually are incidentally detected on colonos-
copy or in colonic resection for other pathology.
Methods: We report the case of a 62 years old male, admitted in the Background & Objectives: We aimed to analyse the distribution,
outpatient clinic of County Hospital with hemorrhoidal disease and sensitivity, specificity, positive and negative predictive values of
rectoragy. A colonoscopy examination was performed which showed frozen sections in GI pathology in our institution for a period of
multiple sigmoidal polyps. For this reason, he was referred to the 3 years.
Surgery Department for surgical intervention. A sigmoid segmentary Methods: Between 1st Jan 2016 to 31st Dec 2018, 1704 frozen sections
colectomy was performed and sent to the Pathology Department. (FS) were carried out in gastrointestinal oncosurgery, out of overall total
Results: Grossly, a 5 cm soft polypoid lesion was identified, with a smooth 14740 FS; constituting 11.6% of total workload. The frozen section di-
surface, on cross-section having a multicystic appearance and clear fluid agnoses and their paraffin section diagnoses are noted from the records.
content. Histologically, a submucosal multilocular cystic lesion was ob- Results: Cholecystectomy specimen for primary diagnosis and common
served, with overlying normal colonic mucosa. The cystic spaces, separated bile duct cut margin (402 cases;23.6%) was the commonest FS; followed
by variable thickness fibrous septa, were lined by a single layer by gastrectomy margins (318cases;18.66%), followed by margins of co-
of endothelial cells, positive immunohistochemically for D2-40. lorectal resection specimen(300cases,17.60%). Other FS requests includ-
Focally we observed a cuboidal cell and giant multinucleated cells ed Whipple surgery for margin, peritoneal nodule biopsy, liver biopsy,
lining, positive for CD68 marker. lymph node biopsy etc. (constituting approximately 684cases;40.14%).
Conclusion: We present a unique case found in our Department. The However, if all organ surgeries are considered, (colorectal, stomach, pan-
particularity of the case consists of the fact that colon cystic creas, extrahepatic bile duct excision), margin assessment was the most
lymphangiomas are extremely rarely found in the elderly, especially in frequent ( 41.8%) FS request (713 out of 1704).
the sigmoid colonic segment. Also, to our knowledge, this is the second The accuracy of FS when compared with paraffin report was 96.77% (35
study to describe the histiocytic replacement of endothelial lining as a discordant cases out of total 1704 cases; 91.71% sensitivity, 99.69%
sign of spontaneous resolution. specificity, positive predictive value of 98.84%, negative predictive value
of 97.68%). Commonest discrepancies were in peritoneal biopsy inter-
pretation and primary diagnosis of gall bladder.
E-PS-06-044 The reasons for discrepancies included superficially cut tissue, scanty
Hepatoid adenocarcinoma of the colon: a case report and literature tissue, sampling error and interpretation error due to freezing and
review crushing artefacts.
S.A. Postolache1, M. Svrcek1, Y. Parc2, R. Cohen3 Conclusion: Cholecystectomy for primary diagnosis and cut margins are
1
Department of Pathology, Saint-Antoine Hospital, Paris, France, 2 the commonest FS requests in GI pathology. We can attempt to avoid
APHP Sorbonne Universitè, France, 3 Department of Oncology, Saint discrepancies by studying deep cuts, careful sampling and being cautious
Antoine Hospital, Paris, France of the artefacts.
 Virchows Arch

E-PS-06-046 scan with contrast showed strong and regularly thickness in the
Comparison of clinicopathological and molecular features between middle third of the oesophagus due to an oesophageal stenosis lon-
left-sided and right-sided colon adenocarcinoma ger than 6 cm.
E. Cakir1, D. Unal Kocabey1, N. Ekinci2, A. Avci2, A. Akder Sari2 The oesophagus and gastric biopsy revealed an invasive non-keratinized
1
Izmir Katip Celebi University Ataturk Training and Research Hospital squamous cell carcinoma of the oesophagus (nuclear expression for p63)
Department of Pathology, Turkey, 2 Izmir Katip Celebi University and a diffuse gastric carcinoma - signet-ring cell carcinoma (tumoural
Ataturk Training and Research Hospital Department of Pathology Izmir cells positive for pancytokeratin, AE1/AE3 and mucin stain - PAS-AA).
Turkey Conclusion: During the initial study, physicians should consider the pos-
sibility of a double cancer. Therefore, reporting such cases in the future,
Background & Objectives: Colon cancer is among the leading will increase our knowledge to avoid misdiagnosis and delayed therapy
causes of cancer-related deaths all over the world. Recent data for the double cancer cases.
suggest that right-sided colon cancer (RSCC) and left-sided colon
cancer (LSCC) have different clinicopathological and biological
features and should be considered as two distinct disease entities. E-PS-06-048
This study aimed to compare the clinicopathological parameters Adenosquamous carcinoma of perianal region: an unusual site of
and molecular features between right and left-sided colon occurence
adenocarcinomas. G. Sahraoui1, L. Bouzidi1, L. Charfi1, R. Doghri1, K. Mrad1, M. Driss1
1
Methods: We reviewed resected colon adenocarcinoma cases from Salah Azaiez Institute, Tunisia
our institutional database; 40 cases of right-sided (cecum, ascend-
ing colon, hepatic flexure, transvers colon) and 54 cases of left- Background & Objectives: Perianal carcinoma is rare accounting for
sided (splenic flexure, descending colon, sigmoid colon). less than 2% of all gastrointestinal malignancies. It may arise de novo or
Parameters including age, gender, histological grade, tumour size, from a fistula or abscess cavity. This is an aggressive cancer often
pT stage, pN stage, lymphovascular invasion, perineural invasion, misdiagnosed clinically as benign pathology.
presence of tumour deposit, mutations of KRAS and NRAS were We report a case of perianal adenosquamous carcinoma to highlight its
analysed. epidemiologic, clinical and pathological features.
Results: The patients with RSCC were older and their tumour size were Methods: A 53-year-old woman with no chronic history of perianal
larger than LSCC but the differences were not statistically significant. fistulas or abscesses was referred to our hospital for management of
KRAS and NRAS mutations were identified respectively in 43.6 % and melena with alternating diarrhea and constipation.
16% of RSCC compared with 25.9 % and 7.5% of LSCC (P=0.118 and Results: Clinical examination and particularly digital rectal examination
p=0.415). Right-sided colon cancers more frequently displayed higher was normal. Colonoscopy did not reveal a rectal or colic tumour. The
histological grade (27% vs 14.9%) compared with LSCC (p=0.185). pelvic enhanced magnetic resonance imaging revealed perianal infiltrat-
There was no statistically significant differences between RSCC and ing tumour. Histopathological evaluation of abdominoperineal resection
LSCC according to gender, lymphovascular ainvasion, perineural inva- revealed an adenosquamos carcinoma arising from perianal glands. The
sion, pT stage, pN stage and presence of tumour deposit. continuity between the anal gland epithelium and the tumour was evident.
Conclusion: Right-sided colon adenocarcinomas tend to show relatively Lymphovascular and perineural invasion was frequent. Surgical margins
larger tumour size, frequent KRAS and NRAS mutation and higher his- were tumourous.
tological grade when compared with left sided colon adenocarcinomas. The absence of associated abscess or fistula was microscopically con-
firmed. Tumour was positive for CK7 and negative for CK20.
Conclusion: Carcinoma of the perianal region is an oncologic rarity
E-PS-06-047 posing a diagnostic and therapeutic dilemma due to very few reported
A rare case of synchronous double cancer in the oesophagus and cases without definite therapeutic guidelines.
stomach
C. Ciora1, M. Cornianu2, S. Taban3,4, G. Oprisan1, M. Iacob5, A.
Ghiughici6 E-PS-06-049
1
Department of Pathology, University of Medicine and Pharmacy "Victor Colorectal cancer: age dynamics of tumour volume
Babes", Timisoara, Romania, 2 V. Babes University of Medicine and A. Filin1, A. Sizov1, V. Danilenko1
Pharmacy, Romania, 3 Emergency Clinical County Hospital ''Pius 1
Voronezh State Medical University named after N.N. Burdenko,
Brinzeu'' Timisoara, Romania, 4 ''Victor Babes'' University of Medicine Department of Pathological Anatomy, Voronezh, Russia
and Pharmacy Timisoara, Department of Pathology, Romania,
5
Department of Pathology, Emergency County Hospital Timișoara, Background & Objectives: Despite the improvement of early diagnosis
Romania, 6 Department of Gastroenterology and Hepatology, University methods, late-stage colorectal cancer is diagnosed in more than 25% of
of Medicine and Pharmacy "Victor Babes", Timisoara, Romania patients, and tumours of stage I–II are detected in less than half of pa-
tients. The aim of the study was to analyse the dynamics of tumour
Background & Objectives: Squamous cell carcinoma of the oesophagus volume in patients of different age groups.
is occasionally associated with other malignancies, particularly of the Methods: 527 patients (238 men, 289 women, average age was 64,7
respiratory tract and the head and neck. Presentation of synchro- years old) suffering from colorectal cancer, underwent primary resection
nous diffuse gastric carcinoma is rare but important to be inves- of the tumour. Based on the data obtained from the description of the
tigated, because stomach is the main organ used for reconstruction removed intestinal fragments, the tumour volume was calculated.
of the alimentary tract after esophagectomies. In cases where there Results: Volume of the tumour varied considerably from 0,1 cm3 to 1650
are synchronous gastric tumours, the colon becomes an option for cm3 (the average volume was 37,3 cm3). The largest tumours were found
transit reconstruction. in the youngest patients (up to 40 years). In all the studied age periods the
Methods: A 66-year-old man, with a medical history of accidental caustic incidence of different volume tumours was similar. Most often, in every 5
ingestion, had presented with appetite loss, dysphagia, epigastric pain and cases (on average 21.5%) in all age groups there are tumours with a vol-
reflux symptoms for several months. ume of 16-32 cm3. Tumours with smaller volumes are less common, with
Results: Oesophagogastroscopy showed an oesophageal stenosis and approximately the same pattern. The largest and smallest tumours are less
a mucosal edema of the gastric angle. Abdominal and thoracic CT common, in 3.5% and 4.6% of cases, respectively. It can be assumed that
Virchows Arch

tumours with a small volume are not common because of their rapid Microscopically, the tumours exhibited tubular and glandular architectur-
progression, and after reaching a certain volume (16-32 cm3, the diameter al pattern, with focal islets and trabeculae. One case presented psammoma
of such foci varies within 2.5-3.5 cm), their growth is significantly bodies in glandular spaces. Tumours were positive for synaptophysin,
inhibited and only in a few cases the tumours grow to giant sizes. chromogranin and somatostatin and presented a low Ki-67 index
Conclusion: The change in tumour volume in colorectal cancer is non- (<10%). SSTR2 reaction was negative.
linear, which can explain the low rates of detection of the tumour in the Conclusion: Given the low incidence of this tumour, its malignant
early stages. potential and the differential diagnosis with adenocarcinoma,
somatostatinoma represents a clinical and morphopathological chal-
lenge. tumoural size may predict the rate of metastasis, but a corre-
E-PS-06-050 lation between a low Ki-67 index and extensive metastases must be
Digestive lymphomas further investigated.
G. Sahraoui1, N. Redissi1, R. Doghri1, L. Charfi1, K. Mrad1, M. Driss1
1
Salah Azaiez Institute, Tunisia
E-PS-06-052
Background & Objectives: Gastrointestinal tract is the most common A single center experience in subepithelial oesophageal lesions (2000-
extra nodal site of lymphomas accounting for 5%-20% of all cases with a 2018)
majority of non-Hodgkin type. The most frequent sites are the stomach T. Cardoso Lima da Costa Pereira1, D. Pereira de Melo1, J. Magalhães1
1
followed by small intestine and ileocecal region. Almost 90% of these Centro Hospitalar Universitário de São João, Portugal
lymphomas are of B cell lineage. Our aim was to report clinical and
histopathological features of digestive lymphomas. Background & Objectives: Subepithelial oesophageal lesions
Methods: We identified cases of digestive lymphomas between January (SELs) are frequently clinically assymptomatic and the vast ma-
1999 and December 2018. jority are incidental findings. The differential diagnosis includes a
Results: Our series included 143 cases of digestive lymphomas. The sex number of benign and malignant nonepithelial tumours.
ratio was 2.3. The average age was 55 years (3-84 years). The most Methods: All cases with diagnosis of SELs registered in our center, from
frequent location was gastroduodenal (86%) followed by rectocolic loca- 2000 until 2018, were collected for review, and six variables were chosen
tion (10%). Concomitant gastric and colonic localization was found in for analysis: age, gender, type of surgical specimen , type of SEL, con-
2% of cases. Ileal site was noted in 1% of cases and anal site in 1% of comitant lesion and follow-up.
cases. Marginal-zone lymphoma was diagnosed in 56 % of cases, large Results: Sixty-four cases were reviewed, fifty-eight of which were from
cell B lymphoma in 39% of cases and Burkitt Lymphoma in 3% of cases. female patients. The mean age at the time if diagnosis was 52,77 years.
Two per cent of cases were difficult typing. Evolution was marked by a The majority had no concomitant lesion (n=51) and had been clinically
transformation of MALT lymphoma into large cell lymphoma in two discharged during follow-up (n=41). Leiomyoma (n=37), followed by
cases and recurrence in 21 cases. granular cell tumour (n=10) and GIST (n=6) were the most common
Conclusion: There has been a tremendous leap in the diagnosis, staging findings and biopsy (n=30) was the most common type of surgical
and management of these lymphomas attributed to a better insight into specimen.
molecular aspect and the knowledge about its critical signaling pathways. Conclusion: An eighteen-year review at our center demonstrated that
most SELs occurred in female patients and had no associated lesions.
Leiomyoma was the most frequent lesion, wich is compatible with the
E-PS-06-051 data described in the literature.
Somatostatin-producing neuroendocrine tumours of the duodenum:
clinical aspects, histological features and immunohistochemical pro-
file - two case reports E-PS-06-053
A. Cohn1, G. Terinte-Balcan1, M. Manuc2, V. Enache3, C. Iosif3, G. The effect of pathological changes in the intestinal wall on the trans-
Becheanu3 location of microorganisms in rats with strangulation intestinal
1
Emergency University Hospital, Bucharest, Romania, 2 Fundeni obstruction
Clinical Institute, Bucharest, Romania, 3 Victor Babes National Institute M. Tusupbekova1, D. Amanova1, P. Ivachyov1, A. Lavrinenko1, Y.
of Pathology, Bucharest, Romania Turgunov1
1
Karaganda Medical University, Kazakhstan
Background & Objectives: Somatostatinoma is a rare neuroendocrine
tumour, derived from the delta-cells of the pancreas or the endocrine cells Background & Objectives: The aim is studying the effect of histological
of the digestive tract. We report two cases of sporadic well-differentiated changes in intestinal wall on the microbial translocation in strangulated
duodenal somatostatinoma, one of them with pancreatic invasion and intestinal obstruction (SIO).
multiple hepatic metastases, diagnosed at Victor Babes National Methods: 30 male rats were divided into 3 groups: I (BT+) - 12
Institute of Pathology. rats with SIO model and present bacterial translocation, II (BT-) –
Methods: We present two somatostatin-producing endocrine tumours of 12 rats with model SIO and absence of translocation, III- 6 rats
a 42-year-old male and a 50-year-old female, which were evaluated ac- of the sham group (laparotomy without model). The SIO model
cording to location, morphology and immunohistochemical profile. was created under general anesthesia by clipping the loop of
Stains for synaptophysin, chromogranin, somatostatin, Ki-67 and small intestine and feeding mesentery for 60 min with a further
SSTR2 were performed. reperfusion for 2 hours. Translocation detection was carried out
Results: The female patient underwent upper endoscopy for abdominal after injection of suspension of fluorescent E. coli with further
pain, which evidentiated a duodenal ulcerated lesion with infiltrative pat- microbiological examination of homogenized organs. Morphological
tern. Imagistic exams revealed a tumoural mass of 47/37/32 mm situated study of intestine and mesentery was performed by the “Leica DM
near the ampullary region, invading the head of the pancreas, hepatic 1000” microscope. The significance of differences was determined by
metastases and lymph node enlargement. tumoural markers CA 125, Fisher's exact test.
CA 15-3 and CA 19-9 were increased. Two months later, the patient Results: In 10(83.3%) cases of BT+ group histologically in the intestinal
started chemotherapy. There was no evidence of neurofibromatosis type wall was observed desquamation and necrosis foci in all layers of the intestine
I. No clinical data were available for the male patient. up to muscular, vascularization of mesentery, perivascular lymphocytic
 Virchows Arch

infiltration, in 2 (16,65%) the process is also organic with a submucosal layer Results: The patient underwent surgery of the gastric and liver masses.
with point foci of necrosis of the muscular layer. In the BT- group morpho- Pathology report showed in both lesions: A proliferation of monotonous
logical picture in 11(91.6%) is represented by damage to the layers of intes- spindle cells arranged in fascicles. Immunohistochemistry showed posi-
tinal wall to submucosal and intact muscular layer, edema of mesentery. tivity for: DOG1, CD117 and CD34 and negativity for: SMA, S100 and
Morphologically changes were not found in the sham group. desmin; Ki67: 10%.
Conclusion: Thus, the fact of the BT is associated with the depth of The final Diagnoses was: Gastrointestinal stromal tumour of the stomach
defeat of intestinal wall, the presence of muscle necrosis leads to bacterial (13cm) with liver metastases.
translocation (p<0.05). Conclusion: Approximately 40% to 50% of gastrointestinal stromal tu-
mour (GIST) patients will have recurrence or metastases after surgical
Supported by Grant Ministry of Education and Science Republic of removal of the primary lesion. The most common affected sites are liver
Kazakhstan and peritoneum.Imatinib has been propose as the first line therapy for
metastatic GIST, however surgery for metastases should be considered
when is possible. The long –term outcome of GIST patients with liver
E-PS-06-054 metastases remain unknown.
Long term survivor of ampullary undifferentiated carcinoma with
osteoclast like giant cells
S. Giusca1, I.D. Caruntu1, D. Ciobanu1, A.D. Timofte1, A. Rusu1 E-PS-06-057
1
"Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania High grade appendiceal mucinous neoplasm
M. Chantziara1, X. Grammatoglou1, S. Pappa2, D. Mpouklas1, A.
Background & Objectives: Undifferentiated carcinoma with osteoclast- Kostopoulou1, E. Gettimis3, T. Choreftaki1
1
like giant cell (UCOGC) is a rare heterogeneous tumour defined by the Department of Surgical Pathology/General Hospital of Athens,
presence of two populations, the mononuclear pleomorphic tumour cells "G.Gennimatas", Greece, 2 Department of Cytology/General Hospital
and non-tumour multinucleated giant cells (MGC), with a recently ac- of Athens, "G.Gennimatas", Greece, 3 1st Department of Surgery/
cepted good prognosis. It was described in numerous organs, more fre- General Hospital of Athens, "G.Gennimatas", Greece
quently in pancreas; few cases located in Vater ampulla are reported.
Methods: We report a case of a 45 years old male patient, admitted for Background & Objectives: We present the case of a 63-year-old male
jaundice in a surgical department in February 2009. Abdominal ultra- patient with high grade appendiceal mucinous neoplasm.
sound revealed a solid mass and dilated distal common bile duct leading Methods: The patient presented to the emergency department
to periampullary tumour suspicion. Subsequently, Whipple procedure complaining of severe pain on his right lower quadrate (RLQ) of the
was performed by surgeons. abdomen with duration of 12 hours. Standard laboratory examination
Results: Gross examination of the pancreatoduodenectomy specimen showed mild leukocytosis. The radiological examinations revealed a di-
revealed a focally ulcerated intestinal mucosa and a solid, white tumour lated appendix. The patient underwent appendectomy.
of 2 cm diameter, involving the ampullary area, duodenal wall and adja- Results: Microscopic examination revealed replacement, focally, of the
cent pancreas. Histopathological exam showed an epithelial proliferation normal appendiceal epithelium by mucin-producing columnar epithelium
composed from individual pleomorphic spindle or round-ovoid cells with low or high grade dysplasia in a micropapillary or cricriform growth
forming trabeculae or discrete duct-like structures chaperoned by pattern, loss of lamina propria and muscularis mucosae with submucosal
scattered MGC with benign appearance, mainly located intraampullary fibrosis and pushing invasion into the muscularis propria. Τhe remnant
with limited pancreatic invasion (<0.5 cm). Immunohistochemically, the epithelium was ulcerative. Pools of acellular mucin were found into the
pleomorphic tumoural cells were positive for CK AE1/AE3 and muscularis propria and mesoappendix.
Vimentin; MGC cells were positive for CD68 and Vimentin, and negative Conclusion: High-grade appendiceal neoplasms (HAMNs) are rare tumours
for CK AE1/AE3; immunostaining for LCA, CK7, CK20, and CDX2 that resemble LAMN in lacking destructive invasion, but show high-grade
was negative. The final diagnosis was ampullary UCOGC, stage III A. cytologic features. This term has been recommended in a recent consensus
The patient had a good clinical course with no metastasis or local recur- publication and has been included in the AJCC 8th edition.
rence till July 2017, qualifying as a very long term survivor.
Conclusion: Our case report confirms the good clinical course of ampul-
lary UCOGC, and completes the limited data available on this entity. E-PS-06-058
HER2 status in paired of gastric biopsies and resection specimens: is
biobsy reliable for prediction of HER2?
E-PS-06-056 M.E. Kara1, E. Uzun1
1
Liver metastases of gastrointestinal stromal tumour (GIST): a case Gaziantep University Medical Faculty Hospital, Department of
report and literature review Pathology, Turkey
V. Caamaño 1 , E. Camacho 1 , R. Ruiz 1 , B. Atares 1 , I. Saenz de
Santamaria1, J. Aguirrre1, A. Perez1, I. Gorostiaga1, A. Martinez1, N. Background & Objectives: In breast and stomach cancer, HER2
Barriobero1, L. Lorente1 oncoprotein overexpression is very important for prognosis and treatment.
1
Araba University Hospital, Spain HER2 protein overexpression is thought to increase that proliferation activity
and suppress apoptosis of the malign cells. Therefore Trastuzumab/HER2
Background & Objectives: Gastrointestinal stromal tumour is the most treatment is a choice for patients with advanced stage/metastatic gastric
frequent mesenchymal tumour in the gastrointestinal tract, accounting for cancer. Since these patients are usually inoperable at diagnosis, it is important
1% to 3% of all gastrointestinal neoplasms following gastric and colorec- to accurately and reliably determine HER2 status. For HER2 analysis, some-
tal cancer. times the only available material can be small biopsies. The aim of this study
Methods: 72 years old woman with a history of abdominal discomfort for is to determine the reliability of HER staining applied to biopsy materials for
and weight loss over the last two months. Physical exam showed abdom- the decision of HER2 treatment in patients with gastric cancer.
inal pain at abdominal palpation. The resonance magnetic images (MRI) Methods: HER2 status in paired of 35 gastric biopsy and resection ma-
demonstrated a 13cm mass on the stomach and also 0,7cm on the liver. A terials were examined. The HER2 stained cases were confirmed by silver
fine needle aspiration biopsy of the gastric mass was performed and it was in situ hybridization (SISH). The result of resection specimens was con-
diagnosed as: Gastrointestinal stromal tumour (GIST). sidered as a gold standard.
Virchows Arch

Results: The concordance of HER2 status between biopsy and gastrec- resection was performed. Macroscopically ten polypoid lesions were seen
tomy materials was 91%. In biopsy materials, there was no false positive throughout the ileal mucosa. The polpys’ sizes varied between 1 cm to
case, while three cases showed false negativity. The positive predictive 3cm. The mucosal surface’ colour was brown. Ulcerated areas between
value of biopsy material was 100% and the negative predictive value was the polyps and deep fissur-like ulcers were also seen.
91.8% in determining HER2 status. Results: Histopathologic examination of the polypoid lesions revealed
Conclusion: In determining the HER2 status, the biopsy materials pro- poorly differentiated adenocarcinoma containing mucinous component
vide accurate and reliable data. In discordant cases, the tumour heteroge- on the background of Crohn’s disease. 8 of the polyps were high grade
neity is accepted as the main cause. tubulovillous adenoma which were complicating with adenocarcinoma.
Some of them were inflammatory pseudopolyps There were also deep
lineer fissurs, pyloric metaplasia, cyript distortion, thickened muscularis
E-PS-06-059 mucosa, neuronal hyperplasia, submucosal fibrosis, linear arranged lym-
Prevalence of oesophageal squamous papillomas (ESPs) in Romania: phoid follicules in submucosa and in subseroza in nonneoplastic bowel
a 12 year multicentric retrospective study compatible with Crohn’s disease.
A. Evsei1, C. Rosianu1, N. Copca1, C. Gheorghe2, M. Diculescu2, M. Conclusion: Crohn’s disease may be presented as adenocarcinoma first.
Dumbrava2, B. Codruta2, I. Bancila2, V. Herlea 2, V. Enache3, S. In the case of adenocarcinoma of small bowell, adjacent mucosa should
Enache 3 , F. Vasilescu 3 , F. Andrei 3 , A. Birceanu 4 , C. Iosif 4 , A. evaluated for CD carefully.
Dumitru5, M. Sajin5, G. Becheanu3
1
CESITO Center, Saint Mary Clinical Hospital, Bucharest, Romania,
2
Gastroenterology and Hepatology Center, Fundeni Clinical E-PS-06-061
Institute, Bucharest, Romania, 3 Victor Babes National Institute, Stomach: an unusual presentation of glomus tumour; a case report
Bucharest, Romania, 4 Pathology Department, Saint Mary Clinical E. Apaydin Arikan1, A.N. Yildirim1, R.B. Girgin1, I.M. Leblebici2, O.
Hospital, Bucharest, Romania, 5 Pathology Department, Emergency Alimoglu2, G. Kir1
1
University Hospital, Bucharest, Romania Istanbul Medeniyet University, Department of Pathology, Turkey,
2
Istanbul Medeniyet University, Department of General Surgery, Turkey
Background & Objectives: Oesophageal squamous papillomas (ESPs)
are rare epithelial tumours with an uncertain etiology and a variable re- Background & Objectives: Glomus tumour is a mesenchymal tumour
ported incidence. Chemical, mechanical and viral agents have been pro- usually occurs in the peripheral soft tissue, especially in subungal region.
posed as a mechanism of pathogenesis with recent reports arguing in Although gastric glomus tumours are extremely rare, it is important to be
favor of malignant transformations, but so far there is little information aware of this entity because of involving in the differential diagnosis of
on a direct cause for this lesion. gastric submucosal tumours.
Methods: We reviewed all patients who underwent an upper gastrointes- Methods: We report a 42-year-old women presenting with anemia.
tinal endoscopy as part of a multicentric retrospective study which com- Results: Endoscopy revealed a submucosal mass at the antrum, but
prised four clinical and research institutions. We collected a total of 123 endoscopic biopsy taken from the lesion was nondiagnostic. A com-
cases of microscopically confirmed ESPs over a period of 12 years (2006- puted tomography showed a well-demarcated solid mass and a gas-
2018). Our purpose was to establish a more precise incidence of this tric wedge resection was performed with the initially diagnosis of
lesion in Romania and to find evidence for a possible link to tumour gastrointestinal stromal tumour (GIST). In macroscopic examina-
progression. tion, underlying the normal appearing mucosa, a 2.8x2.7x2 cm mu-
Results: According to our data, clinical and pathological diagnosis of ral mass was observed. Microscopically, it was composed of solid
ESP was highest in 2013 (18,69%) in all four centers. Female patients sheets and island of small, round to oval uniform cells with very
were more affected than male patients with a 1,3:1 sex ratio. More than suspicious for neuroendocrine tumour. Immunohistochemically, tu-
90% of lesions were under 5 mm and the age category most often affected mour cells were strongly positive with smooth muscle actin and
was between 26 and 50 years old. 88% of cases were single lesions and focally positive with CD34. Neuroendocrine tumour and GIST were
their typical location was found in the distal third of the oesophagus (71 excluded based on the negativity of chromogranin, synaptophysin,
cases). 20,32% cases associated lesions in other locations such as CD117 and DOG1. S100, HMB45, melan-A, desmin and caldesmon
Helicobacter pylori associated chronic gastritis, reactive gastritis, gastric were also negative.
hyperplastic polyps etc. Conclusion: Pre-operative diagnosis of gastric submucosal lesions can be
Conclusion: ESPs are unusual, frequently benign lesion that are still challenging and glomus tumour should be considered in the differential
under debate regarding their mechanism of pathogenesis. Despite their diagnosis. The light microscopic findings of glomus tumour may mimic
rarity, their potential for malignant transformation warrants an attentive neuroendocrine tumour, epithelioid GİST and leiomyoma. Combination
approach to endoscopic, pathological and clinical management. of histological and immunophenotypic findings is crucial for proper di-
agnosis.

E-PS-06-060
Multifocal small bowel adenocarcinoma which is developed in the E-PS-06-062
setting of Crohn's disease: a case report Duodenal gastrointestinal stromal tumour: clinical, histopathological
C. Ozturk1, T.B. Ozcan1, H.E. Pasaoglu1 and immunohistochemical features - a series of 5 cases
1
Bagcilar Training and Research Hospital, Turkey G. Terinte-Balcan1, A.M. Cohn1, S. Enache2, V. Herlea3, G. Becheanu3
1
Emergency University Hospital, Bucharest, Romania, 2 Victor Babes
Background & Objectives: Small bowell adenocarcinoma occurs very National Institute of Pathology, Romania, 3 Fundeni Clinical Institute,
rarely in patients with Crohn’s disease (CD). Here multifocal small bowel Bucharest, Romania
adenocarcinoma developed in the setting of CD is presented.
Methods: 62 year old male admitted to our hospital with persistent ab- Background & Objectives: The term “gastrointestinal stromal tumour”
dominal pain after an hernia operation. In clinical history the patient had (GIST) was first used by Mazur and Clark in 1983. They represent the
intermittant abdominal pain that migt related with inflammatory bowel most common mesenchymal neoplasm of the gastrointestinal tract. They
disease but colonoscopic examination was not performed before. Small are usually found in the stomach (50-60%) and in the small intestine (30-
bowell perforation was detected in emergency laparotomy. Ileum 40%). Duodenal GISTs represent less than 5% of all cases.
 Virchows Arch

Methods: We conducted a retrospective study of the duodenal GIST Background & Objectives: Gastric cancer is the most common malig-
diagnosed at Victor Babes Institute of Pathology, Histopathology and nant tumour. Males are affected 1.3 times more than women, and the age
Immunohistochemistry Department between 2015 - 2019 and selected 5 of patients is usually 50 years and older. MMR definition in gastric cancer
cases. We used the following criteria in order to evaluate them: age, sex, plays important prognostic role.
macroscopy, histology and presence of metastases. Furthermore, we per- Methods: The study based on material obtained after surgery in Moscow
formed a large panel of immunohistochemical markers, which included at Botkin hospital, and the group was 107 patients (age range 31-82) with
least DOG1, CD34, CD117 and Ki67. surgical gastric resection during 2018, where MMR was evaluated. IHC
Results: Of the 5 cases, one of them was male. The median age was 64.2 panel of 4 antibodies was used including MLH1, MSH2, PMS2, MSH6.
years (range 48 – 80 years). The size of the tumours varied between 1 and Results: MMR was identified in 14 out of 107 cases. Type of MMR was
9 cm, with an average size of 2.9 cm. All cases were described as a MLH1-/PMS2- (11/14), PMS2- (3/14). No cases was negative both pro-
proliferation of spindle cells, organized in whorls or short intersecting teins MSH2 and MSH6, or MSH2 or MSH6. Histologically was signif-
fascicles. The mitotic count was less than 5/50 HPF. The tumours were icant predominance of Adenocarcinoma (total -12, G1-1, G2-2, G3-9), 2
positive for CD117, DOG1 and CD34, except for one case that was cases belonged to signet ring cell carcinoma. 11 of 14 of MMR+ tumours
positive only for CD34. had pT3 stage, 1 - pT2 , 2 - pT4a stage.
Conclusion: GISTs located in the duodenum represent a very rare entity Conclusion: In our study of gastric cancer MMR was 13% cases. There
and require a high level of suspicion in order to be correctly diagnosed. were no cases of Lynch Syndrome or other family abnormalities.
The prognosis of this tumour is uncertain, mainly because of the small
number of cases that have been reported so far.
E-PS-06-066
Gastric plexiform fibromyxoma - a mimicker of GIST: a case report
E-PS-06-063 E. Caranfil1,2, D.G. Ciobanu Apostol1,2, D.I. Franciug2
1
24 neuromas of the appendix: a study of retrospective appendectomy "Grigore T.Popa" University of Medicine and Pharmacy, Iasi, Romania,
2
specimens in King Chulalongkorn Memorial Hospital Emergency County Hospital Spitalul Sfântul Spiridon Iași, Romania
D. Thirabanjasak1, L. Sansopha2
1
Department of Pathology, Faculty of Medicine, Chulalongkorn Background & Objectives: Gastric plexiform fibromyxoma is a rare and
University and Chulalongkorn Hospital, Thailand, 2 Department of unique tumour of the stomach located mainly in the antrum. Up
Pathology, Chulalongkorn Hospital, Faculty of Medicine- to date less than 100 cases have been reported. Most patients
Chulalongkorn University, Thailand present with anemia, melena, hematemesis, abdominal pain and
distension. We present a case of a 34-year old woman, admitted
Background & Objectives: Neuromas of the appendix or so-called fi- to the emergency department for melena and moderate anemia.
brous obliteration, the common benign finding of appendectomy speci- Endoscopy followed by CT scan revealed an antral mass
men that is not harmful but charming to the pathologist. Neuromas of the suspected to be a GIST. Gastroduodenostomy (Bilroth I) was sub-
appendix is a unique pathologic lesion. The lesion is composed of prolif- sequently performed.
eration of S-100 positive spindle cells, admixed with benign adipocytes Methods: Tissue samples were routinely processed. HE stains and im-
and fibrous stroma. The lesion is commonly found in both appendectomy munohistochemical tests were performed.
specimens and surgically removed specimens. Awareness of neuromas of Results: Grossly the gastric fragment presented a nodular intramural
the appendix should be helpful for surgery planning in eldery or related tumour (5,1x4,7x2,6 cm) with mucosal ulceration. Microscopically, the
risky patients. tumour presented multiple submucosal and intramural nodules, with plex-
Methods: Retrospective study for appendix specimen was examined, iform growth, composed of bland spindle cells, with low mitotic activity
during 2014-2018. Archives in Department of Pathology, Faculty of situated in an occasionally collagenous fibromyxoid stroma, with
Medicine, Chulalongkorn University and King Chulalongkorn proeminent small vessels and lymphoplasmacytic inflammatory infiltrate.
Memorial Hospital found 1,641 cases of appendix. 24 cases of neuromas The adjacent gastric mucosa presented features of chronic gastritis and
of the appendix, 24 cases of mucinous neoplasm of appendix, 9 cases of incomplete intestinal metaplasia.
diverticulum of the appendix, 6 cases of neuroendocrine tumour of the The tumour cells were diffusely positive for SMA, H-caldesmon, focally
appendix, 3 cases of endometriosis at the appendix, 1 Kaposi Sarcoma at positive for Desmin, CD10. DOG1, CD117, CD34, ALK 1 stains were
the appendix, 1 lymphoma at the appendix, minority of metastatic carci- negative.
noma and the rest is about the inflammation of the appendix (both appen- Conclusion: Plexiform fibromyxoma is a rare entity with good prognosis
dicitis and periappendicitis). 24 neuromas of the appendix were studied, and follow-up data of cases do not report recurrence or metastases. It
with IHC for S-100 and NSE. should be distinguished from GIST which could have an aggresive course
Results: Patients with neuromas of the appendix is majority female and requires a different follow-up and treatment.
(Sixteen female and eight male). The minimum age is 21 and the maxi-
mum age is 87. Mean age is 56.75. Diameter and length of the appendix
were studied (Length : min 3.0 cm, max 7 cm, and mean 4.3 cm) E-PS-06-067
(Diameter : min 0.3 cm, max 0.7 cm, mean 0.44 cm). The spindle cells Poorly differentiated gastrooesophageal carcinoma with trilineage
are stained for NSE and S-100. differentiation
Conclusion: Neuromas of the appendix are common and benign finding. It D. Vinha Pereira1, G. Y. Lauwers2, K. Jiang2
1
is one of the most common finding in the appendix that is not harmful. In Pathology Department, Instituto Português de Oncologia de Lisboa
case there is periappendicitis, it should be precaution for surgeon to look for Francisco Gentil, Lisbon, Portugal, 2 Pathology Department, H Lee
any other accompanying condition that can lead to appendicitis-like pain. Moffitt Cancer Center, Tampa, Florida, 33612 USA

Background & Objectives: Gastroesophageal junction (GEJ) is an ana-

E-PS-06-064 tomical controversial location with neither consensual definition nor uni-
Microsatellite instability in gastric cancer versally reproducible landmarks. Neoplastic lesions of this location are
G. Setdikova1, I. Tin'kova1, O. Paklina1, D. Rotin1,2 particularly challenging. Regardless the precise anatomical site of origin
1
Botkin Clinical hospital, Russia, 2 Hospital Haim Sheba, Tel-ha- and ethiopathogenic process, carcinomas of GEJ have similar
Shomer, Ramat Gan, Israel histomorphology and behavior of the correspondent counterparts in
Virchows Arch

oesophagus and stomach. Poorly differentiated carcinomas could include E-PS-06-070

a variety of lineages of differentiation, with distinct prognoses. The iden- Uncommon metastatic disease of colon carcinoma - report of two
tification of each component could be challenging (histopathologically cases
and immunophenotypically), and rarely more than two lineages have R. Caetano Oliveira1, V. Sousa2, î Jesus1, P. Teixeira1, R. Vieira3, M.J.
been reported. Julião1, J.G. Tralhão4, M.A. Cipriano1
1
Methods: We describe the case of a 56-year-old patient presented for Pathology Department, CHUC, Coimbra, Portugal, 2 Institute of
second opinion regarding his recently diagnosed GEJ tumour. The out- Anatomical and Molecular Pathology, Faculty of Medicine of the
side diagnosis stated poorly-differentiated adenocarcinoma. University of Coimbra, Coimbra, Portugal, 3 Dermatology Department,
Results: Review of the outside biopsy identified a poorly-differentiated CHUC, Coimbra, Portugal, 4 Surgery Department, CHUC, Coimbra,
tumour with definitive adenocarcinoma histomorphology and peculiar Portugal
features suggestive of neuroendocrine differentiation; indeed, both were
confirmed (positive CDX2, synaptophysin and chromogranin
immunostains performed at our institute). Remarkably, P40 was also Background & Objectives: Signet ring cell carcinoma (SCRC) of the
positive in foci of cells. The histomorphology and immunophenotypes colon is a rare entity, sometimes in association with a mucinous compo-
are most consistent with trilineage differentiation, a rare and poorly de- nent, which possesses an aggressive potential and even in cases with
scribed entity. complete resection justify a long-term follow-up.
Conclusion: To our knowledge this is the first GEJ carcinoma identified We report two cases of a SCRC with uncommon cutaneous metastases.
in a biopsy with unequivocal simultaneous trilineage differentiation Methods: Two male patients, one with 70-year-old referred to the
(adenoneuroendocrine and squamous differentiation) without a collision Dermatology department for suspicion of perioribitary sweat gland ade-
tumour pattern. We believe that meticulous histomorphological evalua- nocarcinoma and other with cutaneous lesions in the lower right leg. Both
tion and systemic immunohistochemistry are essential in reaching an were previously subjected to colectomy for PCCC of the colon 10 and 15
accurate diagnosis, particularly in the setting of poorly differentiated car- years ago, respectively. None had previous records of metastatic disease.
cinomas in this location. The impact of this subclassification on the clin- Results: Both lesions exhibited a diffuse and poorly cohesive cell neo-
ical management and patient outcome awaits further investigation. plasia, with wide fatty tissue infiltration, without microsatellite instability.
After six months, both patients are alive but with disseminated cutaneous
lesions and under chemotherapy.
E-PS-06-068 Conclusion: Cutaneous metastases of colorectal carcinoma are uncommon
Desmoplastic tumour reaction, inflammatory infiltrate and colorec- and usually reflect advanced disease. The SCRC have a diffuse pattern of
tal cancer: how it works? dissemination, without boundaries respect, avoiding the usual routes of colo-
R.I. Bermudez Cameo1, A. Sobrino Prados1, C. Hondler Argarate1, J.I. rectal metastases – lung and liver, motivating a tight follow-up.
Franco1, M.J. Viso Soriano1, H.P. Almanzar Comas1, S. Bakali Badesa1,
A. Arellano Alvarez1, N. Estrada Mallarino1, L. Ligorred Padilla1, V.
Vazquez Alvarez1, M.A. Nasarre Perez1, A. Perez Ibañez1, L. Lazaro E-PS-06-071
Villanua1, E. Del Valle1, A. Puertas1, M.A. Trigo Cebrian1 De novo colorectal carcinoma after renal and hepatic transplantation
1
Hospital Universitario Miguel Servet Zaragoza, Spain R. Caetano Oliveira1, H. Antunes2, A.M. Abrantes3, E. Tavares Silva2, R.
Martins4, J.G. Tralhão4, E. Furtado5, M.F. Botelho6, M.A. Cipriano1
1
Background & Objectives: A pronounced desmoplastic tumour reaction Pathology Department, CHUC, Coimbra, Portugal, 2 Urology
(DTR) was associated with a reduced immune response, and has been Department, CHUC, Coimbra, Portugal, 3 Biophysics Institute, FMUC,
related to be a poor prognosis indicator in colorectal cancer and cancer Coimbra, Portugal, 4 Surgery Department, CHUC, Coimbra, Portugal,
5
recurrence. However, CRC with a prominent inflammatory infiltrate, Hepatic Transplantation Unit, CHUC, COimbra, Portugal, 6 Biophysics
which is composed of intraepithelial (TIL) and peritumoural (PTL) lym- Unit, FMUC, Coimbra, Portugal
phocytes, is predictive of a better prognosis. This study sought to inves-
tigate the relation between DTR with low rate of TIL and high rate of PTL Background & Objectives: Solid organ transplantation (SOT) is effec-
in CRC. tive for the treatment of certain diseases, however has some risk associ-
Methods: The study included 109 patients with CRC who had undergone ated, namely development of neoplasias. Immunosuppression has been
surgery from 2009 to 2011 at a single institution (University Hospital appointed as higher risk for colorectal cancer (CCR) development.
‘Miguel Servet’ of Zaragoza (Spain)). They were categorized according Our objective is to study the incidence as well as the clinical and patho-
to: TNM protocols of the American Joint Committee on Cancer (AJCC) logical characteristics of de novo CCR after renal and hepatic
as pT3 N0 M0, DTR, TIL and PTL status. Adjustment was made for transplantation.
relate low rate of TIL and high rate of PTL with a pronounced DTR. Methods: Retrospective study of patients with CCR diagnosis at ours
All biopsies were examined with Hematoxylin and Eosin and TIL and institution between Jan/2004 and Dec/2016, previously submitted to
PTL were controlled by CD3 and CD8 immunohistochemistry renal/hepatic SOT.
(Polyclonal Rabbit anti-human CD3- Dako Omnis; Monoclonal Mouse Results: 12 patients (10M:2F), median age 60.54±13.41years, from
anti-human CD8-Dako Omnis). which 9 were submitted to surgery – CCR in the right colon in 5 patients
Results: The 51% of the patients were men (56/109) and 49% were (41.7%) and in the left colon on 7 patients (58.3%), none on rectum.
women (53/109). Also 33% (36/109) of the total group were death by 5 patients were previously subjected to hepatic SOT – incidence 1:151.
the end of this study. Low rate of TIL was present in the 61% of the CCR developed after a median of 55.2±26,13months after SOT, with a
patients with a DTR, in comparison with the 18% with high rate of TIL median of 58±10,19years.
(25/41 and 7/41 respectively). Also 22% had moderate rate of TIL (9/41). 7 patients were submitted to renal SOT – incidence de 1:380. CCR de-
About PTL, only 20% of patients with DTR and low rate of TIL were veloped after a median of 117.85±76.97months, with a median of 61.43
high rate of PTL. ±16.65years. After a median of 16.9±6,7months all the patients are dead.
Conclusion: Low rate of TIL was more frequent in patients with Tumours were mainly of higher stages (N=7), especially in the renal SOT
desmoplastic tumour reaction, which can be explained because of the cohort and revealed overexpression of cancer stem cells (CD133, CD44,
resistance wielded by the tumour reaction in the stroma. However, our ALH1). There were large areas of necrosis and low density of immune
sample was not big enough to conclude with a high impact result, indi- population. There was no expression for PD-L1 and through CD56 expres-
cating the need of further investigations. sion there were no NK cells. 4 patients were MSI and 5 were P53 mutated.
 Virchows Arch

Conclusion: CCR after SOT has an aggressive behavior. Selected cases examinations revelled synchronous polyps, and all were biopsied or sub-
may benefit from individualized therapy; however, surgery and early mitted or polypectomy. The most common type was tubular adenomas
detection seem to be the key. followed by tubulovillous adenomas. The serreated morphology was the
least prevalent.
Conclusion: The screening program is not yet homogenously implanted
E-PS-06-072 in all territory, but the actual sampling is relevant to recognize the
High grade appendiceal mucinous neoplasm; a new classifıcation is favourable prevention and Health Minister commitment.
obligatory Data from other studies revealed that the percentage of positive CCR for
R.B. Girgin1, T. Soylemez1, E. Apaydin Arikan1, H. Seneldir1, G. Kir1 work-up of a positive gFOBT is around 4%, which is in line with our
1
Istanbul Medeniyet Universitesi, Department of Pathology, Turkey results.

Background & Objectives: Epithelial tumours of appendix range in

a wide spectrum and their nomenclature has been a subject of E-PS-06-074
debate for many years. Here we present a case of high grade Sall4 expressing gastric carcinoma with high serum afp level; is it
mucinous appendiceal neoplasm (HAMN) and we want to discuss possible to rule out a burned out yolk sac tumour metastasis?
this entity through this case. R.B. Girgin1, T. Soylemez1, A.N. Yildirim1, E. Apaydin Arikan1, G. Kir1
1
Methods: A 41 years old male patient was admitted to emergency Istanbul Medeniyet University, Department of Pathology, Turkey
service with symptoms of acute abdominal pain. Computerized to-
mography revealed that a dilated cystic lesion of 6 cm diameter Background & Objectives: SALL4 has been identified as a diagnostic
compatible with appendiceal lesion and the radiologists mentioned marker of germ cell tumours. Recent studies showed that SALL4 may act
that they could not rule out a tumoural process . Thus the patient as an onco-fetal or carcinoembryonic molecule İN some neoplasms of
underwent surgery. extragonadal organs. AFP-producing gastric carcinomas accounts for
Results: Intraoperative examination revealed that there was no mucinous 2.7%-5.4% of all gastric carcinomas with some of them containing germ
material in the abdominal cavity. Macroscopically appendix was cell components which explains retrograde differentiation of neoplastic
cystically dilated, creamy white and measured 6x6x4 cm. Microscopic cells.
evaluation revealed that this cystic lesion was lined by papillary and Methods: 60 years-old male patient was investigated for abdomi-
cribriform arranged epithelium. These epithelial cells displayed loss of nal pain. Endoscopic examination revealed an ulcerous lesion at
polarity, full thickness nuclear stratification and high grade cytologic the corpus-antrum junction and the serum AFP level was >20000
atypia. The appendix was totally submitted and did not exhibit infiltrative ng/mL. No mass was detected in testis nor a previous tumour was
invasion. present.
Conclusion: The current WHO classification has no definition that cor- Results: Microscopic examination revealed a poorly differantiated
responds to this entity. Whereas in the litterature, the use of the term “high tumour with focal trabecular areas and with clear cell areas which
grade appendiceal mucinous neoplasms” is encouraged. lacked mucin and glycogen accumulation with Alcian blue and
PAS stain, respectively. Tumour cells were diffusely positive for
CDX2, SALL4, Glipycan 3, AFP and EMA. No mass was detect-
E-PS-06-073 ed in testis nor a previous tumour was present. PET scan was unremark-
Colorectal cancer screening: the center of Portugal stands up with able except stomach.
4,6% incidence in 10 years of experience Conclusion: It should be kept in mind that AFP-producing gastric carci-
V. Almeida1, A. Alarcão1,2,3, A.F. Ladeirinha1,2, M. Reis Silva1,2,3, T. noma and yolk sac tumour share similar morphologic and
Ferreira1,2, A.I. Rodrigues1, V. Sousa1, L. Carvalho1 immunhistochemical features. EMA positivity support the diagnosis of
1
Institute of Anatomical and Molecular Pathology, Faculty of Medicine gastric carcinoma based on the knowledge that germ cell tumours are
of the University of Coimbra, Coimbra, Portugal, 2 CIMAGO - Research negative for EMA.
Center for Environment, Genetics and Oncobiology, Faculty of Medicine,
University of Coimbra, Coimbra, Portugal, 3 Centre of Pulmonology,
Faculty of Medicine of the University of Coimbra, Portugal E-PS-06-075
Clear cell sarcoma of the digestive tract: a case report
Background & Objectives: In Portugal, as in other European countries, R. Narjess1, N. Boujelbene2, I. Abbes2, R. Doghri2, L. Charfi2, N.
the recommended primary screening test for colorectal cancer starts with Kcherem2, K. Mrad2, M. Driss2
1
the guaiac-based Faecal Occult Blood Test (gFOBT) directed to asymp- Institute of carcinology Salah Azaiz Tunis, Tunisia, 2 Department of
tomatic population with no risk factors between 50 and 74 years-old. This Pathology, Salah Azaiez Institute, Tunisia
strategy is followed by total colonoscopy in positive gFOBT cases.
Screening implementation had a previewed raise of colorectal carcinomas Background & Objectives: Clear cell sarcoma (CCS) of the gas-
diagnosed without symptoms. trointestinal tract is a rare malignant neoplasm that occurs in the
Screening of 10 years-period and synchronous lesions were reviewed. wall of the small bowel, stomach, or large bowel, predominantly
Methods: The registry between 2008 to 2018 corresponded to in young adults. It is an aggressive neoplasm that frequently pre-
polypectomies of 1576 patients submitted to a colonoscopy follow- sents with metastatic disease and has a high mortality rate. Herein
ing the positive gFOBT as part of the colorectal cancer screening we report a case of CCS with description of the pathological and
programme. molecular features of this rare entity to make pathologists aware
Colorectal adenocarcinomas and concomitant polyps were reviewed. of this entity.
Results: From the 1576 patients/cases tested, 4,63% (78) were diagnosed Methods: A 27-year-old patient with a history of retinoblastoma
with adenocarcinoma, which is under the 10% recognizes by European consulted for dysphagia.
Union Recommendation on cancer screening (2017). Results: Fibroscopy shows a bulging formation of the middle 1/3 of the
From those 78 cases, 51 belonged to men. The median age of affected oesophagus. Histological examination of a biopsy shows a densely cellular
patients was 64. tumour consisting of rounded monomorphic cells disposed in a vaguely
The most frequent localization was the sigmoid colon. The diagnosed fasciculate pattern. Tumour cells have a round or oval nucleus with a
carcinomas were alone in 33 cases and the other 45 endoscopic reduced eosinophilic clarified cytoplasm. The immunohistochemical study
Virchows Arch

show that these cells are Pancytokeratin (-), PS100 (+), SOX10 (+), Background & Objectives: Apocrine carcinoma is a rare skin append-
HMB45 (-), MelanA (-), Desmin (-), RB1 (+), C-kit (-), DOG1 (-), age tumour that shows apocrine-type decapitation secretion. It occurs in
CD99 (+), SMARCB1 (+). the body sites where apocrine ducts are normally located.
Molecular study identified a EWSR1-ATF1 fusion transcript, which con- Methods: An 88-year-old male presented with a sessile polypoid lesion
firmed the diagnosis of a clear cell sarcoma of the digestive tract. in the anal region. It was 2,5 cm wide, white and firm, and was surgically
Conclusion: The lack of familiarity of pathologists with the features of resected.
this neoplasm may have previously contributed to its under recognition, Results: Lesion was an expansive mass of variable-sized nodules, located
but the finding of an epithelioid or spindle cell neoplasm in or around the in lamina propria, growing in solid and cribriform patterns with eosino-
gastrointestinal tract with S100 protein expression should always warrant philic acellular secretions. Cells had large eosinophilic cytoplasm with
molecular assessment for EWSR1 rearrangement and for EWSR1- pleomorphic nuclei and prominent nucleoli. Numerous mitotic figures
CREB1 and EWSR1-ATF1 fusion transcripts. were identified. The overlying epithelium showed pagetoid spread of
atypical cells, but was not intraepithelial dysplasia. Lymphovascular in-
vasion was present and the resection margin was positive. A few
E-PS-06-076 mammary-type glands were seen, affected by an analogue intraductal
Ceacal adenocarcinoma arising from huge Traditional Serrated lesion. The immunophenotype of the tumour cells was strongly and dif-
Adenoma located in appendix and ceacum: a case report fusely positive for CK7, GCDFP-15, androgen receptor and Her2 (3+),
H.E. Pasaoglu1, E. Erel1, N. Okkabaz2, T.B. Ozcan1, T. Cay1, N. and negative for CK20, CK 5/6, CDX2, p63 and p40.
Erdogan1 Conclusion: Adenocarcinoma with apocrine differentiation arising from
1
Clinical Pathology, Turkey, 2 Gastrointestinal Surgery, Turkey anogenital glands is uncommon and only a few cases have been pub-
lished. Both genders are equally affected. Pathogenesis is unknown, but
Background & Objectives: Traditional serrated adenomas are un- it seems to arise from apocrine hyperplasia or adenoma of anogenital
common, making –up <%1 of all colorectal polyps. They are mammary-like glands. Differential diagnosis includes metastatic breast
usually found in the distal colon . Appendix and ceacum are very cancer, benign apocrine tumours, colorectal adenocarcinoma and mucin-
rare locations for TSA. The majority of TSAs are protuberant ous carcinoma. Treatment is wide excision.
lesions smaller than 2cm. Here, we presented a case of ceacal
adenocarcinoma arising from a huge, broad based traditional ser-
rated adenoma located in appendix and ceacum. E-PS-06-078
Methods: 75 year old female was admitted to clinic with abdom- PDL-1 expression is poor prognostic factor in gastric carcinomas?
inal pain and distention. Physical examination was normal. The S. Erdamar1, S. Bahsi1, Į Yıldız1
1
patient had undergone breast conserving surgery for breast cancer Acibadem University Medical College, Turkey, College, Turkey
four years ago. Colonoscopy revealed a 5 centimeters broad based
polypoid lesion in ceacum. Intramucosal carcinoma arising from Background & Objectives: PDL1 expression and Microsatellite
an adenoma with serrated pattern was seen in colonoscopic biop- Instability (MSI) is getting more important gastric carcinoma to get ben-
sy. Right hemicolectomy was performed. efit from immunotherapy. In this study, we aimed to investigate the MSI
Results: Macroscopically 5,5x4 cm polypoid mass in ceacum was detected. status and the frequency of PD-L1 expression in gastric cancer cases and
Diameter of the appendix was 1,7 cm . Polypoid lesion was connected with the relationship between this frequency and clinicopathological features
the appendiceal orifice. Longitidinal section was performed from the orifice and overall survival.
to the tip of the appendix and fingerlike projections troughout the appendix Methods: The patients diagnosed with gastric cancer between the years
mucosa were seen. Histopathologically the lesion had a villiform growth 2010-2017 at Acibadem University Hospitals were retrospectively
pattern and serrated luminal surface. The cells lining the villi analysed and 86 patients were included in the study. Patients were eval-
were tall and columnar with eosinophilic cytoplasm and pencillate uated of age, sex, tumour location, tumour size, tumour histological sub-
nuclei. Small, abortive ectopic crypts were also seen. These fea- type, clinical and pathological tumour stage, HER-2 staining status, pre-
tures were consistent with TSA. The lesion exhibited high grade operative treatment status, lymphovascular and perineural invasion, re-
dysplasia in some areas . An adenocarcinoma containing mucinous com- section status. Tumour sections were immunostained with MMR proteins
ponent was detected in deep portion of the adenoma in ceacum, which and PD-L1 (22C3 clone). Analytical statistical methods, survival analysis
was infiltrating the subseroza. Immunhistochemically MUC-2, MUC was performed. Factors affecting survival were determined by univariate
5AC were positive, MUC-6 negative and DNA mismatch repair proteins and multivariate analysis.
(MLH1, MSH2, MSH6, PMS2) were diffusely expressed in nuclei in Results: The incidence of MSI was 11.6% (n:10), the presence of PD-L1
both adenoma and invasive carcinoma areas. expression in tumour cells was 34.9% (n:30) and the presence of PD-L1
Conclusion: The diagnosis of TSA may be difficult in small endoscopic expression in immune cells with Combine tumour score (≥1%) was 57%
biopsies. Furthermore, carcinoma in the deep portion of the polyp may (n:49). PD-L1 positivity was found to be statistically higher in patients
not be detected in endoscopic biopsies . Total excision with intact surgical with node positive, adenocarcinoma subtype, microsatellite instability,
margin should be done. preoperative treatment, and chemotherapy response.
Conclusion: In our study, the impact of MSI status on survival was not
demonstrated, but PD-L1 expression positivity was associated with short
E-PS-06-077 survival in both tumour cells (p:0.008) and in immune cells (p:0.027).
Adenocarcinoma of anal glands with apocrine differentiation: a case
report and a literature review
O.B. Popescu1, O. Cerezo-Aranda1, J.M. Barria Castro2, L. G. Pastrián1, E-PS-06-079
E. Palacios Lázaro1 Synchronous presence of epithelial and stromal tumours in the stom-
1
Hospital Universitario La Paz, Spain, 2 Complejo Hospitalario Dr. ach - characterization of molecular pathways
Arnulfo Arias Madrid, Panama E. Kocsmar1, G. Papp2, I. Kocsmar1, L. Szalai3, I. Kovalszky2, G. Lotz1
 Virchows Arch

1
2nd Department of Pathology, Faculty of Medicine, Semmelweis Results: We analysed 243 endoscopic biopsies of 41 children with newly
University, Hungary, 2 1st Department of Pathology and Experimental diagnosed UC as well as specimens after treatment. The average age of
Cancer Research, Semmelweis University, Hungary, 3 2nd Department of patients was 12.8±4.39 years. Majority of patients were male (53.66%).
Pathology, Semmelweis University, Hungary Twelve percent of patients had extraintestinal manifestations of the disease
with the primary sclerosing cholangitis as the most common. Statistical
Background & Objectives: Gastrointestinal stromal tumours (GISTs) analysis showed significant moderate correlation between histopathological
are the most common tumours in the digestive tract arising from the scores and EMS, and significant strong correlation among histopathological
mesenchymal components of the tissue. Small GISTs (GIST tumourlets) scores. We found slightly stronger correlation between histopathological
are usually asymptomatic and most frequently found in gastric surgical scores and EMS in children with newly diagnosed UC than after treatment.
specimens incidentally. Our aim was to assess prevalence of incidental Conclusion: There is strong statistically significant correlation between his-
GISTs among gastrectomy specimens of gastric adenocarcinoma patients topathological scores (Geboes and Nancy). Therefore both of the histopath-
and to obtain data about molecular mechanisms of these synchronous ological scores can be successfully applied in estimation of disease severity.
tumours.
Methods: Gastrectomy specimens obtained between 2002-2018 were
selected from the institutional register of the 2nd Department of E-PS-06-083
Pathology. Incidence of incidental GISTs was also assessed separately Correlation of tumour budds, epidermal growth factor 2 and
according to the method of resection (partial or total). Patients with ade- exspression of E-cadherin with overall survival of patients with ad-
nocarcinoma and synchronous GIST were selected and CD117 (c-kit), vanced gastric adenocarcinoma
CD34 and DOG1 immunohistochemical stainings were performed on M. Cuk1, R. Gajanin2, S. Kulic1, M. Vasic Milanovic3
1
both tumours. KIT exon 9, 11, 13, 4, 17 mutations were analysed by University of East Sarajevo, Faculty of Medicine Foca, Department of
Sanger sequencing. Pathology, Bosnia and Herzegovina, 2 University of Banja Luka, Faculty
Results: 1,027 gastrectomy specimens were analysed in the study period, of Medicine, Department of Pathology, Bosnia and Herzegovina, 3 Public
including 665 cases of patients operated due to adenocarcinoma. Health Hospital, Department of Pathology, Zvornik, Bosnia and
Synchronous incidental GIST was found in ten cases (1.5% of 665). All Herzegovina
of the GIST tumourlets were of spindle cell variant and
immunohistochemically positive with CD117, CD34 and DOG1. Background & Objectives: Adenocarcinoma of the stomach is very
Positive DOG1 immunostain was detected in four adenocarcinomas as aggressive biological behavior and has a poor prognosis in patients in
well. KIT mutation was found in four GISTs, but in none of the synchro- an advanced stage of the disease. Testing new prognostic parameters and
nous adenocarcinomas. discovering new therapeutic targets is a long-standing challenge for pa-
Conclusion: Incidence of incidental GISTs in gastrectomy specimens thologists and oncologists.
was lower in our cohort than in other studies. Although a common carci- Methods: Tumour buds were determined on the invasive edge of the
nogenic effect cannot be ruled out, our data suggest that distinct mecha- tumour and defined as individual or groups of less than five tumour cells.
nisms play role in the development of synchronous GISTs and gastric Paraffin-embedded tumour samples were examined for E-cadherin, CK20
adenocarcinomas. and HER2 using immunohistochemistry. Additionally, gene amplification
was examined using fluorescent in situ hybridization (FISH) for HER2.
This study was partly supported by New National Excellence Program of Results: The minimum follow-up period was 6 months and a maximum
the Hungarian Ministry of Human Capacities (ÚNKP-18-3-I-SE-44), follow-up period of 87 months. The survival rate of patients after 12
EFOP-3.6.3-VEKOP-16-2017-00009, and Semmelweis Start-up months was 80.2%, after 24 months 51%, after 36 months 28.5%.
Research Grant. Budding was present in 76 of 96 cases and was associated with decreased
overall survival (OS) (Log Rank=32,805, p<0.001). Reduced expression
of E-cadherin was identified at the frequency of 74% and was associated
E-PS-06-081 with decreased overall survival (Log Rank=23,80, p<0.001). There was a
Correlation between different histopathological indices and clinical significant difference in OS between HER2-positive and HER2-negative
parameters in children with ulcerative colitis patients [median, 17.0 vs. 26.0 months; p < 0.01]. Multivariate analysis
J. Jevtic1, R. Jankovic2, S. Strizovic2, D. Obradovic1, N. Ristic3, N. showed that high grade of tumour budding was an independent prognos-
Dragutinovic3, I. Milovanovic3, M. Radusinovic3 tic factor for overall survival [hazard ratio, 1,46 (95 % confidence inter-
1
Faculty of Medicine, University of Belgrade, Serbia, 2 Institute of val, 1,25 – 1,69); p<0.01], but HER2 and E-cadherin did not show them-
Pathology, Faculty of Medicine, University of Belgrade, Belgrade, selves as independent prognostic parameters.
Serbia, 3 University Children's Hospital, Serbia Conclusion: Tumour budding is significant and independent predictors
of poor outcomes in patients with advanced gastric adenocarcinoma.
Background & Objectives: A diagnosis of ulcerative colitis (UC) re-
quires multidisciplinary approach. Among wide variety of diagnostic Sunday, 8 September 2019 – Wednesday, 11 September 2019
modalities histopathology still stands as the diagnostic gold standard.
E-PS-07 | Digestive Diseases Pathology – Liver / Pancreas
Since the histological remission is the main goal in treatment of UC,
assessment of disease activity during endoscopy and histopathological
examination is of paramount importance. The aim of the study is to E-PS-07-001
determine the correlation between different histopathological scores Hepatocellular adenoma like associated with vascular obstructive
(Geboes and Nancy) in biopsies of the children with UC, endoscopic disease secondary to alcohol consumption
Mayo score (EMS) and clinical overview. A. Vera-Torres1, L. Barrera2, M. Tapias1, J. Alvarez-Figueroa2
1
Methods: Colonic biopsies of children with UC from the Institute of Transplant and Hepatobiliary Surgery Service, Hospital Universitario
Pathology, Medical Faculty, University of Belgrade were retrospectively Fundación Santa Fe de Bogotá Colombia, 2 Department of Pathology and
analysed, as well as clinical data and endoscopic characteristics collected Laboratory Medicine, Hospital Universitario Fundación Santa Fe de
from University Children’s Hospital in period of three years (2016-2018). Bogotá, Colombia
Virchows Arch

Background & Objectives: Hepatocellular nodules are commonly to chemotherapy and with morphologic remision pending for
observed in hepatic vascular disorders and the lesions that resem- trasplantion.
ble a hepatocellular adenoma share the same characteristics as a Conclusion: Although adult presentations of LCH is described in the
conventional hepatocellular adenoma. We present a lesion that literature this patient's age is unusual. As a morphological finding, we
resembles a hepatocellular adenoma associated with a hepatic shown that the presence of granulomas with histiocytes and eosinophils in
vascular disorder secondary to alcohol consumption. biopsies should be considered as a suspicious finding for LCH and
Methods: 64-year-old man with history of alcohol consumption, diabetes Hodgkin lymphoma and Mastocytosis should, however, be consider in
mellitus and variceal bleeding. The CT scan show liver with normal the differential diagnosis.
contours and diminish of size with prominence of the caudate
lobe, permeable vascular structures and focal poorly defined
25 mm lesion. E-PS-07-003
Results: Liver examination revealed micronodular surface and mi- Intracranial meningeal hemangiopericytoma metastatic to the liver
croscopically heterogeneous architecture, both severe and slight J. Alvarez-Figueroa1, L. Barrera1, A. Vera-Torres2, E. Jimenez-Hakim3, P.
nodular areas, significant sinusoidal dilatation, hemorrhage and Escalante1
1
blood vessels destruction associated with hepatocellular lesions Department of Pathology and Laboratory Medicine, Hospital
with cholangiolar proliferation, chronic inflammation and telangi- Universitario Fundación Santa Fe de Bogotá. Bogotá, Colombia,
ectasia with CD34, FVIII and SAA reactivity, with low cell pro- Colombia, 2 Transplant and Hepatobiliary Surgery Service, Hospital
liferation index and negativity for glutamine synthetase and Universitario Fundación Santa Fe de Bogotá, Colombia, 3 Department
Betacatenin. The reticular pattern was preserved without presence of Surgery, Hospital Universitario Fundación Santa Fe de Bogotá,
of malignant hepatocellular lesion. Colombia
Conclusion: Obstructive vascular disease can be seen in alcoholic
patients. Fibrosis after abstinence may improve and Background & Objectives: Solitary fibrous tumour/The
steatohepatitis characteristics would be lost. Lesions similar to hemangiopericytoma is a mesenchymal central nervous system tumour
hepatocellular adenoma (inflammatory/telangiectasic adenoma of uncommon fibroblastic origin, when the phenotype corresponds to a
morphology) present with an immunophenotype similar to the hemangiopericytoma there is an increased risk of extracranial metastases,
observed on conventional hepatocellular adenoma. This lesion which usually occur several years after the initial diagnosis. We present a
associated with hepatic vascular disorders, may increase the risk case of metastatic meningeal hemangiopericytoma to the liver.
of malignant transformation compared to a conventional hepato- Methods: A 42-year-old female patient with a history of recurrent extra-
cellular adenoma. axial tumour, who presented abdominal induration sensation 9 years after
the initial diagnosis. Multiple solid hepatic lesions with heterogeneous
cystic components and peripheral enhancement were documented on CT
E-PS-07-002 scan. Patient was submited to right hepatectomy and segmental resection
Adult hepatic Langerhans cell histiocytoris associated with chronic of lesions in the left lobe.
colangiopaty Results: Histopathological study reveladed a malignant, hypercellular
M. Rolon1, M. Romero1, C. Saavedra1, D. Cañon1,2, L. Barrera1, A. Vera- mesenchymal neoplasm, consisting of cells with rounded to oval nuclei,
Torres3, M. Tapias3, J. Alvarez-Figueroa1 vesicular and condensed chromatin, some cells with epithelioid appear-
1
Department of Pathology and Laboratory Medicine, Hospital ance, arranged in a disorganized architectural pattern, thin-walled blood
Universitario Fundación Santa Fe de Bogotá, Bogotá, Colombia, 2 vessels cells and up to 8 mitosis in 10 HPF. Immunohistochemical
Universidad de los Andes. Bogotá, Colombia, showed diffuse and strong positivity of neoplastic cells for CD34, BCL-
3
Transplant and Hepatobiliary Surgery Service, Hospital Universitario 2, CD99 and Vimentin, with focal and weak positivity for Progesterone
Fundación Santa Fe de Bogotá. Bogotá, Colombia Receptors and negativity for EMA and Desmin.
Conclusion: These findings correspond to a meningeal mesenchymal
Background & Objectives: Langerhans cell histiocytosis (LCH) is a rare tumour of hemangiopericytic morphology, which is part of the solitary
neoplasm characterised by the presence of positive CD1a histiocytes. fibrous tumour/hemangiopericytoma spectrum, and it is classified as
Predominates in the paediatric age with cutaneous lesions as the first WHO 2016 grade III, metastatic to liver. These tumours should be con-
manifestation. We present a case of an adult with hepatic involvement sidered as potentially malignant in all cases and hepatic metastases are
associated with chronic damage of the bile duct without cutaneous rare.
manifestations.
Methods: 47-year-old male with history of diabetes insipidus and one
year of multiple episodes of acute cholangitis associated with abdominal E-PS-07-004
pain, jaundice, high bilirubin direct levels, transaminases and alkaline Solitary fibrous tumour hepatic: case report and review of current
phosphatase. AMA negative. The cholangioresonance reveled global he- knowledge
patomegaly with alteration of parenchymal intensity and stenosis of the R.M. Souza da Silva1, E. Moreira de Queiroga2, A. Rolim da Paz3,
intrahepatic bile duct. Á. Regina Gouveia4
1
Results: Liver biopsy showed architectural distortion, portal fibro- Federal Fluminense University, Brazil, 2 Alcides Carneiro University
sis, portal spaces with inflammatory infiltrate composed by Hospital of the Federal University of Campina Grande, Brazil, 3
histiocites, lymphocites, plasma cells, foamy histiocytes and abun- University Hospital Lauro Wanderley/EBSERH/UFPB, Brazil, 4
dant eosinophils, granulomas and bile duct damage with aberrant Faculty of Medical Sciences, Brazil
expression of cytokeratin 7 at periportal level and ductular reac-
tion with acute cholangiolitis. Hepatocanalicular cholestasis, Background & Objectives: Solitary fibrous tumours (SFTs) are a rare type of
xanthomatous change with periportal copper deposits. CD1a and spindle cell neoplasm, composed of cellular and collagenous components,
s100 positivity in the portal histiocytes. The patient was subjected predominantly arise from the pleura. SFT of the liver (SFTL) are uncommon
 Virchows Arch

with little number of cases reported in English literature. The diagnosis is with other synchronous tumours is furthermore exceptional, the case of
based on histological and morphological characteristics, associated with im- our patient.
munohistochemical markers and molecular analysis. The rarity of this tumour Methods: 59-year-old man, consulting for chronic abdominal pain, ra-
makes it difficult to evaluate its prognosis and natural course. Surgical resec- diological investigations showed a large exophytic pancreatic tumour.
tion remains the mainstay of treatment. The patient underwent surgery, he has had caudal spleno-pancrectectomy.
Methods: The present study reports a new case of SFTL and has the main In gross, there was a voluminous exophytic pancreatic tumour, well lim-
purpose of updating the current knowledge. ited, firm, appended to the tail; and presenting an heterogeneous cut
Results: 42-year-old woman, with right hypochondrial discomfort and surface.
postprandial fullness. Magnetic nuclear resonance showing nodular ex- The spleen was increased in size, 20 cm of large, with homogeneous
pansive formation with well-defined contours, located in left hepatic lobe. appearance.
Macroscopically, a nodular mass, white color, firm and elastic, measuring Results: Histological examination of the pancreatic mass and the immu-
3,2 cm x 3,0 cm.. Microscopic examination evidenced fusocellular pro- nohistochemical study concluded to a gastrointestinal stromal tumour of
liferation, hypocellular and hypercellular areas (mild atypia), with pre- moderate risk of malignancy, expressing DOG 1 and CD
dominance of a sclerotic pattern. The immunohistochemical study re- 117.Examination of the spleen showed an infiltration by large granular
vealed ki-67 1%, positivity for STAT 6, CD 34 and Bcl-2. The diagnosis T lymphocytes, with large nuclei, these cells expressed in immunohisto-
was of Solitary Fibrous Tumour Hepatic. chemistry T markers: CD2, 3, CD7 and 8 and show a loss of CD4 ex-
Conclusion: The SFTL is rare, with only 85 cases reported in the English pression. . The molecular biology study confirms the diagnosis by show-
Literature including the present case. The clinical presentation is habitu- ing a clonal rearrangement of the TCR gamma and betta genes.
ally indolent. The diagnosis is histopathological e immunohistochemical. Conclusion: The association of stromal tumours with other neoplasia
SFTL because due to its rarity, its clinical presentation, study, treatment, must search for common carcinogen or genetic predisposition, multicen-
and prognosis are not well known. ter studies involving a large number of cases are necessary to confirm or
refute this hypothesis.

E-PS-07-005
Chylous ascites, induced by a pancreatic carcinoma E-PS-07-007
A.C. Tinca1, Tivadar Bara1, Ioan Jung1, Simona Gurzu1 The analysis of mortality at gallstone disease according to autopsy
1
Department of Pathology, Clinical County Emergency Hospital, Tîrgu studies
Mureș, Romania Department of Pathology, University of Medicine, T. Vervekina1,2, B. Magrupov2
1
Pharmacy, Sciences and Technology, Tîrgu Mureș, Romania Republican Research Center of Emergency Medicine, Uzbekistan,
2
Tashkent Institute of Postgraduate Medical Education, Uzbekistan
Background & Objectives: Chylous ascites is an uncommon condition
of peritoneal cavity. The aim of the paper was to describe the case of a Background & Objectives: The problem of gallstone disease in the
patient with ductal adenocarcinoma of the pancreatic body that presented structure of the morbidity grows steadily. Surgical activity at this pathol-
as acute abdomen and chylous ascites. ogy surpassed the number of other abdominal interventions including
Methods: A 76-year old previously healthy male presented with acute appendectomy. Complicated forms of the disease and combined pathol-
abdomen and suspicion of pancreatic body cancer, with associated asci- ogy increase the level of cholelithiasis in the structure of mortality.
tes, was done. Emergent surgery consisted on splenopancreatectomy with Methods: We performed analysis of 2674 patients’ case histories with
dissection of the peripancreatic lymph nodes. The fluid from abdominal various forms of cholecystolithiasis. Fatalities were recorded in 18 patients
cavity had a milky aspect and was proved having lymphatic origin. at the age of 41-60 years, 13 of them were 51-60 years old men. Analysis of
Results: The 50x40x20 mm pancreatic tumour involved the pancreatic lethal outcome was carried out according to the results of autopsy studies.
body and tail and showed direct infiltration of the spleen hilum, being Results: We found that in 89% of cases an unfavorable outcome occurred
diagnosed as pT3N1 ductal adenocarcinoma. Most of the lymph vessels at the combination of various forms of cholecystitis and choledocholithi-
showed tumour emboli, which induced blockage of the lymphatic flow. asis. In the gallbladder were diagnosed: destructive forms of inflamma-
The patient died at three weeks after surgery. tion (11 cases), chronic cholecystitis (4), chronic recurrent cholecystitis
Conclusion: In patients with pancreatic cancer, chylous ascites can indi- (3). The third part of the lethal outcomes was in patients with a combined
cate an aggressive carcinoma with lymphatic flow blockage. pathology, such as liver cirrhosis, myocardial infarction, peptic ulcer, and
heart disease. The death cause in most cases was sepsis, as well as com-
This work was supported by a grant of the Romanian National Authority plications of combined diseases.
for Scientific Research, CNCS – UEFISCDI, project number 20 Conclusion: The analysis showed that deaths are more often recorded in
PCCF/2018, code: PN-III-P4-ID-PCCF-2016-0006. 51-60 years old men with destructive forms of cholecystitis at a lesion of
the gallbladder and choledoch. Combined pathology of the digestive or-
gans and cardiovascular systems has a significant impact on the disease
E-PS-07-006 outcome.
Synchronous pancreatic stromal tumour and granulous T-cell leukemia
A. Bdioui Thabet1, C. Pierre2, H. Busby2, N. Mhamedi2
1
Georges Pompido Hospital Paris, France, 2 Brabois Hospital, Nancy, E-PS-07-008
France A rare case of signet-ring cell carcinoma of the gallbladder, present-
ing as Krukenberg tumours of the ovaries
Background & Objectives: Coexistence of stromal tumours with other M. Kilmpasani1, I. Matzarakis2, A. Baliaka1, I. Dimitriadis2, N. Pastelli2,
malignancy is rarely reported, it has been described for digestive stromal I. Karafoulidou2, S. Despina2, V. Penopoulos2, S. Papaemmanouil2
1
tumour with adenocarcinoma, either MALT or Hodgkin lymphoma. Extra Department of Pathology, General Hospital of Thessaloniki "G.
digestive stromal tumour are rare counting less than 5%, Their association Papanikolaou", Greece, Thessaloniki "G. Papanikolaou", Greece, 2 2nd
Virchows Arch

Surgery Department, General Hospital of Thessaloniki "G. Results: Mean value of Ki-67 index was 0.4% ± 0.2% in normal liver,
Papanikolaou", Greece 3.52% ± 0.2% in non-tumour liver lesions and 13.4% ± 7.7% in HCC
(p<0.001). Mean value was 5.2% in portal chronic hepatitis and 5.5% in
Background & Objectives: Signet-ring cell carcinomas of the gallblad- active chronic hepatitis with cirrhotic evolution.
der are very rare and considered to have an aggressive behaviour. 66.6% of HCC associated with HBV infection and 66.6% of HCC devel-
Krukenberg tumour of the ovary may be the first manifestation of a oped from a cirrhotic lesion had a high Ki-67 score. High proliferation
malignancy, and is associated with poor prognosis. We report the case rate was correlated with presence of intrahepatic metastasis (p<0.001) and
of a 49-year-old woman, admitted with bilateral ovarian tumours, without with vascular invasion (p<0.001).
any known gallbladder-related symptoms. Conclusion: Differences between the proliferation rate of HCC and non-
Methods: During the surgical oophorectomy, a simultaneous cholecys- tumour liver lesions (p<0.001) show that the uncontrolled division of
tectomy was performed, due to suspected metastasis to cystic duct lymph tumour cells can play an important role in the development of HCC.
nodes. Ki-67 expression as a prognostic factor can be used to select the right
The surgical specimens were examined in FFPE sections with therapy for hepatocellular carcinoma and may be a future target for mo-
hematoxylin-eosin and immunohistochemical stains. lecular therapy.
Results: Two white-tan lesions of the gallbladder mucosa were observed,
each measuring 1.5cm. The microscopic examination revealed a signet-
ring cell carcinoma, beginning from the overlying epithelium and infil- E-PS-07-010
trating the gallbladder wall. Two cystic duct lymph nodes showed metas- Epstein Barr Virus-associated smooth muscle tumour: a case report
tasis from the carcinoma. C. Fumagalli1, E. Chenu1, S. Novelli1, J.C. Pernas1, A. Mozos1, J.
Both ovaries demonstrated nodular, solid, white-tan tumours, measuring Szafranska1
1
10cm (right) and 2cm (left). The microscopic findings were similar to the Hospital de la Santa Creu i Sant Pau, Spain
aforementioned carcinoma in the gallbladder. Among others, the neoplas-
tic cells stained positive for Ck7 and Ck19, and negative for Ck20, Background & Objectives: Epstein Barr virus associated smooth mus-
vimentin, CD15 and a-fetoprotein. cle tumour (EBV-SMT) is an under-recognized entity that usually occurs
Consequently, the ovarian tumours were diagnosed as metastases of the in immunosuppressed patients. Herein, we present a case of EBV-SMT
carcinoma of the gallbladder. affecting a post-transplant female.
Conclusion: It is a challenge to differentiate primary from metastatic Methods: The patient, an 18-year-old female with a history of T-cell
carcinoma of the ovaries. Krukenberg tumours are ovarian tumours of lymphoproliferative disorder, was treated with bone marrow transplant
metastatic origin, with a diffuse infiltration by signet-ring cells. A primary in 2012. In CT scan, a well-defined mass (44 mm) was found in the liver
malignancy in the gallbladder is rarely encountered. Only few cases of and, due to its hypervascular pattern, a tru-cut biopsy was performed.
primary signet-ring cell carcinoma of the gallbladder are described in the Histological examination showed a neoplasm consisting of spindle cells
literature, and they are frequently associated with locally infiltrative be- arranged in small fascicles with elongated cigar-like nuclei and an eosin-
haviour and distant metastases. ophilic cytoplasm. No cytological atypia was found and the mitotic ac-
tivity was low (Ki67<5%).
Results: Immunohistochemistry highlighted that tumoural cells
E-PS-07-009 expressed smooth muscle actin and caldesmon. In situ hybridization for
Immunohistochemical study of cell proliferation in hepatocellular Epstein-Barr virus (EBV) was strongly positive, while the EBV protein
carcinoma late membrane protein 1 (LMP1) was negative. Based on these findings,
R.A. Barna1, M. Cornianu2, D. Lazar3, N. Basa4, S. Taban5,6, A. EBV-SMT was diagnosed. A conservative management was established
Dobrescu7, F. Lazar8,9 and the patient was treated with Sirolimus. A control performed five
1
Department of Pathology, University of Medicine and Pharmacy months later showed persistence of active EBV infection and stability
„Victor Babes", Timisoara, Romania, 2 V. Babes University of of the lesion. Nonetheless, due to collateral effects, immunosuppressive
Medicine and Pharmacy, Romania, 3 Internal Medicine Department IV, therapy was retrieved.
University of Medicine and Pharmacy „Victor Babes", Timisoara, Conclusion: EBV-SMT has been described in patients infected with HIV,
Romania, 4 Internal Medicine Department I, University of Medicine in the posttransplant setting, and in those with congenital immunodefi-
and Pharmacy „Victor Babes", Timisoara, Romania, 5 Emergency ciency. In the present case it affected the liver of an immunosuppressed
Clinical County Hospital ''Pius Brinzeu'' Timisoara, Romania, 6 ''Victor patient. Due to its rarity, it might inadvertently be misdiagnosed as a
Babes'' University of Medicine and Pharmacy Timisoara, Department of leiomyoma. There isn’t an established treatment for this tumour, but a
Pathology, Romania, 7 Surgery Department II, University of Medicine correct diagnosis would avoid overtreatment.
and Pharmacy „Victor Babes", Timisoara, Romania, 8 Surgery
Department II, "Victor Babeş" University of Medicine and Pharmacy,
Timișoara, Romania, 9 Surgery Department II, Emergency County E-PS-07-011
Hospital Timișoara, Romania Histological features and dynamics of colorectal metastasis in the
liver
Background & Objectives: The aim of this study was to evaluate the C. Fumagalli1, E. Chenu1, B. Martin1, I. Gich1, D. Paez1, J.C. Pernas1, V.
proliferative activity of neoplastic and non-neoplastic hepatocytes, to Artigas1, J. Szafranska1
1
identify possible correlations between histopathological features of Hospital de la Santa Creu i Sant Pau, Spain
HCC and its proliferation rate and to establish the role of Ki-67 as a
prognostic factor in patients with radical surgery of HCC. Background & Objectives: Colorectal cancer (CRC) is the third most
Methods: Assessment of the proliferative activity was made using mono- prevalent cancer worldwide and liver is the most common site of CRC
clonal Ki-67 antibody, clone MIB-1 ready-to-use. To appreciate the pro- metastases (CRCLM).Hepatic resection of CRCLM remains the standard
liferation index of Ki-67 (PI Ki-67), it has been used the semi-automated of treatment, sometimes associated with neoadjuvant chemotherapy (NC).
method of counting the nuclei on digital images. Aim of the study was to analyse histological features within the
The study included 32 surgically removed liver carcinomas. In order to metastases, in the tumour-liver interface (TLI) and in the non-
compare results, it was included a group of non-tumour lesions obtained tumoural liver parenchyma, in order to identify how the metastases
by liver biopsy. modify the liver histology.
 Virchows Arch

Methods: The clinical history and histologic parameters were revised of E-PS-07-013
131 CRCLM resected at our institution during the period 2010-2017. The A rare case of primary inferior vena cava leiomyosarcoma mimick-
study included 95males and 48females with a median age of 67yrs and a ing hepatocellular carcinoma presentation
tumour median size of 2,9cm.Among them, 82(62,6%) received NC.The O. Neagu1, M. Grasu2, M. Dumbrava2, R. Cerban2, V. Herlea2, G.
histological features studied were: mucinous component, vascular- Becheanu2,3
1
perineural-biliar invasion, growth pattern, fibrous capsule, ductular pro- University Emergency Hospital Bucharest, Romania, 2 Fundeni Clinical
liferation and chronic inflammation with/without lymphoid follicles in Institute Bucharest, Romania, 3 "Victor Babes" National Institute of
TLI and presence of portal-centrilobular-lobular inflammation, hepato- Pathology, Bucharest, Romania
cyte ballooning-acidophilic bodies, fibrosis, colestasis and rosette forma-
tion in liver parenchyma. Background & Objectives: Primary leiomyosarcoma of the inferior ve-
Results: Statistical analysis was performed dividing the patients in group na cava (IVC) is a rare malignant tumour, with less than 400 cases re-
A (who received NC) and B (without NC).It was found that NC was ported so far. It has a slow progression and becomes symptomatic at an
associated with replacement growth pattern, absence of chronic inflam- advanced stage, justifying its poor prognosis once detected. Clinical pre-
mation and fibrous capsule in TLI (p <0.005),while in group B surgical sentation depends on tumour location along the IVC, divided into three
hepatitis and rosette formation (p <0.005) in the no-tumoural liver paren- segments by Kulaylat.
chyma were observed. No differences in overall survival were found Methods: We report a case of a 61-year-old male, diagnosed 6 months
when comparing the growth pattern or the use of NC. prior with an IVC thrombosis, who was admitted for a liver tumour
Conclusion: Both CRCLM and NC could induce liver changes.In evaluation. CT examination revealed a 65/50 mm tumour, involving the
this study, it was found replacement growth pattern, absence of VI-VII segments, the IVC and the abutting right atrial wall. Another
chronic inflammation and fibrous capsule in TLI in pts who received similar small lesions were also noted in the right lobe, highly suggesting
NC, while more prominent surgical hepatitis was curiously found in a hepatocellular carcinoma.
pts who didn’t receive NC. However, further research is required to Results: The liver biopsy showed a spindle cell proliferation with
understand de complex mechanisms taking place within the metasta- eosinophilic fibrillary cytoplasm and large pleomorphic nuclei
tic liver. with scattered atypical mitoses. Ancillary immunohistochemistry
tests showed positive tumour cells reactions for smooth muscle
markers (SMA, desmin, H-caldesmon) and negative reaction for
E-PS-07-012 CD117, DOG1 and CD34, advocating for a leiomyosarcoma.
The conclusive utility of cell-block procedure in diagnosing rare pan- Thoroughly systemic investigation didn’t find any other conceiv-
creatic neoplasms through EUS-FNA approach able primary site for the liver tumour. Considering the aforemen-
O. Neagu1, M. Dumbrava2, B. Cotruta2, I. Bancila2, V. Herlea2, C. tioned findings, the conclusive diagnosis was a leiomyosarcoma
Gheorghe2, G. Becheanu2,3 of the third segment of the IVC with extra- and intraluminal
1
University Emergency Hospital Bucharest, Romania, 2 Fundeni Clinical growth.
Institute, Bucharest, Romania, 3 "Victor Babes" National Institute of Conclusion: Although IVC leiomyosarcoma is more common among
Pathology, Bucharest, Romania women and usually affects the first two segments, the presentation herein
was distinctive. The mainstay treatment is complete surgical resection
Background & Objectives: EUS-FNA has become the gold stan- with a customized approach. Given the tumour extension in our reported
dard in preoperative pancreatic masses assessment. Nevertheless, case, a palliative chemotherapy scheme is currently administered, with no
rare pancreatic neoplasms display indefinite morphology on routine tumour progression so far.
cytologic smears, even for experienced cytopathologists. Adding the
cell-block procedure increases the diagnosis accuracy by enabling the
use of ancillary tests. E-PS-07-014
Methods: We report two cases of isthmus and body pancreatic neoplasms Solid and pseudopapillary neoplasm of the pancreas: pathological
detected during abdominal sonography in a 23-year-old and 66-year-old characteristics of 5 cases with Imaging correlation
women, respectively. An EUS-FNA was performed and the cytologic A. Bdioui Thabet1, A. Fourati2, N. Mhammedi3, S. Benkhlifa3, M.
material obtained was used for routine cytologic smears and one cell- Mokni3
1
block. Georges Pompido Hospital Paris, France, 2 Sahloul Hospital of Sousse,
Results: The rapid-HE stained smears showed loose clusters and Tunisia, 3 Farhat Hached Hospital of Sousse, Tunisia
single cells with finely granular cytoplasm and hyperchromatic nu-
clei with fine chromatin, resembling neuroendocrine cells, with min- Background & Objectives: Solid pseudopapillary neoplasm of the
imal to moderate atypia, insufficient for diagnosis. The cell-block pancreas is a rare tumour often detected initially on imaging. Of
cellular material revealed a solid pattern with thin vessels throughout, uncertain histogenesis, it has a low-grade malignant potential with
scattered rosette-like or intact papillary structures with fibrovascular excellent post-surgical curative rates and rare metastasis.
components. The cells were displayed in a perivascular fashion. In Pathological evaluation remains the gold standard in reaching a
one case, we also identified fragments of liver tissue and gastric definitive diagnosis. On morphology alone, other primary pancre-
mucosa with normal architecture. Positive immnunohistochemistry atic tumours pose a diagnostic challenge. Recent advances in im-
reactions for beta-catenin, CD56, androgen-receptor, vimentin and munohistochemical characterization have made the histopathologic
negative reactions for E-cadherin, AE1/AE3 and chromogranin con- diagnosis more specific and, shed light on the likely histogenesis
firmed the diagnosis of a solid pseudopapillary pancreatic neoplasm of this rare tumour.
(SPN). Results: 5 patients included 4 females and 1 male, with a median age of
Conclusion: SPN is a rare entity, comprising less than 2.7% of all pan- 48.5 years. CT scan was performed showed a pancreatic well limited mass
creatic tumours. It mainly affects young women and the common location measuring between 4 and 17 cm. A peripheral capsule was seen and some
is the tail of the pancreas. In the reported cases, presentation and cytology calcifications were detected and none of the patients was found to have
appearance weren’t conclusive for this pathology. The aid of a cell-block hepatic and lymph nodes metastases. In one case an hemorrhagic content
procedure lead to the correct diagnosis, giving the possibility of immu- was noticed. Microscopic examination and the immunohistochemestry
nohistochemistry tests and haematoxylin-eosin staining equivalent to his- study confirmed the diagnosis of solid pseudopapillary neoplasm in all
tological slides. cases.
Virchows Arch

E-PS-07-015 removal because of the frequent occurrence of squamous metaplasia

Hepatocellular adenomas in a cirrhotic liver: report of an unusual and possibility of squamous cell carcinoma.
case
C. Araújo1, J. Cristóvão2, A. Figueiredo3, A. Carvalho4
1
Centro Hospitalar Universitário Lisboa Central, Portugal, 2 NOVA E-PS-07-017
Medical School, Lisboa, Portugal, 3 Serviço de Anatomia Patológica - Inflammatory myofibroblastic tumour of the pancreas - case report
Hospital Curry Cabral, Centro Hospitalar e Universitário de Lisboa R. Gajanin1, V. Gajanin1, I. Sladojević1, M. Cuk2
Central, E.P.E., Portugal, 4 Hospital Curry Cabral, Centro Hospitalar 1
University of Banja Luka, Faculty of Medicine, Bosnia and
Universitário Lisboa Central, Portugal Herzegovina, 2 University of East Sarajevo, Faculty of Medicine,
Bosnia and Herzegovina
Background & Objectives: Hepatocellular adenoma (HCA) is a liver
tumour usually presenting in young females undergoing oral contracep- Background & Objectives: Inflammatory myofibroblastic tumours
tion. HCA occurs mostly against the background of healthy and disease (IMT) are rare mesenchymal proliferative lesions, built of
free liver. Herein, we report a case of a 73-year-old male patient with myofibroblasts and inflammatory cell infiltrate in the stroma, of
multiple HCA-like lesions in the setting of a cirrhotic liver. unknown etiology and prognosis. They can be found in all ana-
Methods: A 73-year-old male with a past history of arterial hypertension, tomical regions, most commonly in the lungs, and very rarely in
dyslipidemia, type 2 diabetes mellitus and oesophageal varices was in- the pancreas.
vestigated for anemia and cholestasis and performed a computed tomog- Methods: We report a case of a 51 years old woman with IMT localized
raphy that revealed four nodules in the IV and V hepatic segments, the in the pancreatic head. Clinical manifestations included abdominal pain,
largest one with 4cm. nausea, yellowing of the skin and mucous membranes, and newly diag-
Results: The liver biopsy showed a cirrhotic liver, but the definite diag- nosed diabetes. Using MRCP, we saw a dilatation of the intrahepatic and
nosis of the hepatic nodules was not possible. The patient was submitted extrahepatic bile ducts and a soft tissue change with unclear boundaries,
to a hepatic bissegmentectomy. Histology revealed nodules of hepatocel- localized in the pancreatic head, 9 cm in diameter. The surgical treatment
lular proliferation with preserved reticulin framework, normal thickness included pancreatectomy and splenectomy.
of the trabeculae, unaccompanied arteries and absence of portal tracts. Results: Macroscopically, the tumour change was located in the pancre-
CD34 expression was patchy, glutamine synthetase confined to atic head, had a yellow-whitish color, sized 9.5 x 4.5cm. Morphologically,
perivenular hepatocytes and no nuclear expression of beta-catenine , it was built by spindle cells with storiform and fascicular arrangements
p53 or HSP70. The final diagnosis was compatible with hepatocellular and mixed stromal inflammatory infiltrate. Immunohistochemical analy-
adenoma-like nodules in a background of cirrhosis with features of sis showed positive staining for SMA, Calponin, Desmin, and ALK, and
steatohepatitis. A close follow-up of the patient was recommended. negative for Myogenin, S-100, H Caldesmon, and CD117. The diagnosis
Conclusion: Nodules that deviate in appearance, size and behavior from of IMT in the pancreas with peripancreatic extension in the connective
the conventional spectrum of large regenerative nodules, dysplastic nod- tissue was established, with negative resection margins. The patient is 18
ules and hepatocellular carcinoma in cirrhotic livers are very rare and only months without recurrence of the disease.
a handful of cases of HCA in the background of cirrhosis have been Conclusion: IMT is rare in the pancreas. So far, 32 cases were published
described. Despite this, this possibility needs to be considered, in order in the English language literature. Presurgical differentiation from other
to avoid the risk of misdiagnosing and subjecting patients to incorrect neoplastic lesions is difficult and usually requires resection and histolog-
treatments. Extensive sampling and immunohistochemistry are funda- ical analysis. Morphologically, it is necessary to differentiate IMT from
mental to achieve a correct diagnosis. fibrosarcoma, adenocarcinoma, lymphoma and chronic pancreatitis.

E-PS-07-016 E-PS-07-018
Foregut origin ciliated cyst of the gallbladder Mixed adenocarcinoma and neuroendocrine carcinoma of the gall-
H. Dincer1, E. Yarıkkaya1, N. Dursun2 bladder: next generation sequencing suggests a monoclonal origin
1
University of Health Sciences, Department of Pathology, Turkey, F.M. Sta. Ines1, A.L. Anceno1, R.A. Salamat1, N. Navarro Jr.1, G.L. Pua1,
2
University of Health Sciences, Istanbul Health Practice and Research J.J. Andal1, D. Ang1
1
Hospital, Department of Pathology, Turkey St. Luke's Medical Center, Philippines

Background & Objectives: Foregut origin ciliated cysts of the gallblad- Background & Objectives: Mixed adenoneuroendocrine carcinoma
der are very rare, benign, cystic lesions. They are usually located above (MANEC) of the gallbladder is a rare tumour that is defined by the
the diaphragm but they can also arise in relation to the liver, gallbladder presence of a neuroendocrine carcinoma or neuroendocrine tumour,
and pancreas. admixed with an adenocarcinoma, each component constituting at
Methods: A 62-year-old women was referred to our hospital’s surgery least 30% of the neoplasm. MANEC's histogenic classification
clinic with symptoms of chronic abdominal pain. On abdominal ultraso- remains unclear. We present a case of a 74 year-old Filipino
nography and computed tomography, multiple calculi was found. The woman who presented with right upper abdominal pain and fever.
gallbladder was resected through laparoscopic cholecystectomy. Whole abdominal CT scan demonstrated a distended multiseptate gall-
Results: Grossly, the cystic lesion, measuring 0,6x0,6x0,3 cm, was locat- bladder and a 1.1 cm. non-enhancing faintly hyperdense ovoid focus
ed in the neck of the gallbladder. The cyst had no communication with the (suggestive of cholelithiasis versus sludgeball) within the body. She sub-
lumen. Microscopically the histopatology showed that the cyst was lined sequently underwent open cholecystectomy.
by pseudostratified ciliated columnar epithelium. These findings led us to Methods: Histopathologic examination of the cholecystectomy specimen
diagnosis of ciliated foregut cyst. revealed two morphologic and immunophenotypic components: a mixed
Conclusion: Ciliated foregut cysts are rare anomalies due to aberrant well-differentiated adenocarcinoma (30%) and a poorly differentiated
embryological development. Characteristically, most of the cases are large cell neuroendocrine carcinoma (70%). The adenocarcinoma and
middle-aged females and unilocular lesions. Ultrasound is an efficient neuroendocrine tumour components were carefully microdissected sepa-
method of imaging for hepatobiliary masses. There are a few reports of rately, and next-generation analysis was performed on both components,
squamous cell carcinoma arising in the ciliated foregut cyst, however using Illumina Trusight 15 Tumour (TST) kit and sequenced on Illumina
there is no reports in the gallbladder. Foregut cysts requires surgical MiSeq.
 Virchows Arch

Results: The tumour showed a high mitotic rate of 83 mitosis per 10 high uid-lled, thin-walled, unilocular cyst. The cyst was lined by a single layer
power fields and extensive necrosis. Immunohistochemical studies of cuboidal to columnar cells, with uniform, round nuclei with occasional
showed the neuroendocrine component to be reactive to synaptophysin small nucleoli and eosinophilic, granular cytoplasm, which formed small
and chromogranin. Mutational analysis of selected targeted regions of 15 acinar structure with eosinophilic PAS-positive cytoplasmic granules.
cancer associated genes identified a TP53 missense mutation that leads to The cyst wall was collagenous with no evidence of ovarian-type stroma.
a stop codon (c.273G>A, p.Trp91Ter) in both components. Immunohistochemical stains showed the cyst-lining cells were trypsin
Conclusion: The molecular genetic similarities of the two morphologi- and chymotrypsin, Muc6 positive. These findings confirmed the cytolog-
cally different components of the tumour supports the hypothesis that ical diagnosis of an acinar cell cystadenoma.
MANEC arises from a common precursor stem cell capable of divergent Conclusion: We report an unusual case of a cystic lesion of the pancreas
phenotypic differentiation. lined by acinar cells with mucinous metaplasia, consistent with the diag-
nosis of acinar cell cystadenoma. Acinar cell carcinoma is an uncommon
malignant tumour accounting for 1% to 2% of all exocrine pancreatic
E-PS-07-019 neoplasms. This lesion can be added to the list of unilocular cystic neo-
Splenic vein leiomyosarcoma: a case report plasms of the pancreas.
F. Filipello1, G. Fiorentini2, C. Doglioni3,1, M. Schiavo Lena3
1
Vita-Salute San Raffaele University, Milan, Italy, 2 Pancreatic Surgery
Division, IRCCS San Raffaele Hospital, Milan, Italy, 3 Pathology Unit, E-PS-07-021
Division of Experimental Oncology, IRCCS San Raffaele Scientific Cystic neuroendocrine tumour of the pancreas: a misleading variant
Institute, Milan, Italy D. Chiba1, S. Chaieb2, S. Mestiri2, O. Belkacem2, S. Yacoub2, N.
Abdessayed2, B. Sriha2, M. Mokni2
1
Background & Objectives: Leiomyosarcoma (LMS) is an aggressive Department of Pathology Farhat Hached Hospital, Tunisia, 2 Farhat
mesenchymal tumour originating from smooth muscle. Primary pancre- Hached Hospital, Tunisia
atic LMS has been reported in the literature, nevertheless it is a rare entity.
Venous origin for LMS is an extremely uncommon site of origin of LMS, Background & Objectives: Pancreatic neuroendocrine tumours
mostly affecting the inferior vena cava and only five cases arising from (PanNETs) are rare neoplasms that comprise up to 5% of pancreatic
the splenic vein have been described. We present a case of primary splenic malignancies. Cystic PanNETs are a distinctive subgroup with unique
vein LMS. clinical and pathological features.
Methods: We report the case of a 51 year-old women who presented to Because of their cystic nature, preoperative radiological diagnosis of this
San Raffaele Scientific Institute with non-specific abdominal pain. entity continues to be a challenge to differentiate them from others pan-
Abdominal computed tomography showed a 27x15 mm solid tumour in creatic lesions like cystic neoplasms.
the body of the pancreas, in proximity to the splenic vein. Afterward, the The clinical and histopathologic characteristics of cystic PanNETs are
patient underwent ecoendoscopy with cytological examination that indi- poorly defined which motivated us to present this case report.
cated the mesenchymal nature of the lesion. Distal pancreatectomy and Methods: We present a 54-year-old man with no significant history in
splenectomy were performed and subsequent histopathological whom we found incidentally a tumour in the tail of the pancreas, by
examination. abdominal ultrasonography.
Results: Morphological and immunohistochemical investigations Computed tomography revealed a well-defined cystic lesion in the tail of
showed a moderately differentiated LMS originating from the splenic pancreas measuring 45 mm of diameter.
vein, infiltrating the pancreatic parenchyma with three lymph nodes in- A mucinous cystic lesion was suspected and considering the malignat
volved by contiguity. potential of this tumour, the patient had a distal pancreatectomy without
Conclusion: Venous splenic LMS is a rare entity, nevertheless it can be a prior cytological diagnosis.
difficult differential diagnosis from other pancreatic mesenchymal tu- Results: Macroscopically, the surgical specimen was constituted of a
mours. In order to make a correct diagnosis, care must be taken for the distal pancreatectomy measuring 10 X 6cm, containing on cut section a
anatomical localization of the tumour from early diagnostic steps. Careful multilocular cystic mass with a hemorrhagic content.
macroscopic evaluation and exhaustive sampling are fundamental to A definite diagnosis of neuroendocrine neoplasm was confirmed by micro-
identify the structure of origin, to be confirmed microscopically. scopic and immunohistochemical findings using synaptophysin ,
chromogranin. Grading of the tumour was based on mitotic index and ki67,
and the tumour was classified according to the ENETS2010/OMS 2017, as
E-PS-07-020 G1 well differentiated neuroendocrine tumour with cystic component.
Acinar cell cystadenoma of the pancreas Conclusion: Cystic PanNETs are a distinctive subgroup of PanNETs
G. Setdikova1, O. Paklina1, A. Karpov1, M. Tavobilov1 with unique clinical and pathologic features. Because of their cystic na-
1
Botkin Clinical Hospital, Russia ture, these neoplasms often present a radiologic preoperative diagnostic
dilemma.
Background & Objectives: Acinar cell cystadenoma is a rare, benign Recently, endoscopic ultrasonography guided fine needle aspiration
cystic lesion of the pancreas that can affect almost any age group. First (EUS-FNA) was reported to be useful for preoperative definitive diagno-
described in 2000 by Klöppel using the term acinar cell cystic transfor- sis. But until now; the definitive diagnosis remains only histological
mation, the term acinar cell cystadenoma was first proposed by Albores- reinforced by immunohistochemistry.
Saavedra, as the lesion was postulated to be the benign precursor of acinar
cell cystadenocarcinoma.
Methods: We present a case of acinar cell cystadenoma in a 67-th men. E-PS-07-022
Results: A 67-year-old man was admitted to our hospital complaining of Intestinal immunophenotype in pancreatic cancer: true or fall?
abdominal distension. He had no history of alcohol intake, acute pancre- G. Setdikova1, O. Paklina1
1
atitis, or trauma. Serum carbohydrate antigen (CA) 19.9 and Botkin Clinical hospital, Russia
carcinoembryonic antigen (CEA) was normal. Computed tomography
(CT) showed a cystic mass with an irregularly thickened wall of up to Background & Objectives: To study the immunophenotype ducts of the
43 mm. No pancreatic duct dilatation or peripancreatic inammatory pancreas in embryogenesis and taking into account the data obtained to
changes were identied. Enucleation was remarkable for a 40 mm pussy analyse the immunophenotype of pancreatic ductal adenocarcinoma.
Virchows Arch

Methods: We examined the expression of MUC1, 2,5AC, CK8, CK7, objective is to determine the effect of these parameters in an ultrasound
CK20, CDX2 by immunohistochemical analyses in pancreas ducts at study on the volume of the liver, calculated according to the formula J.T.
different weeks of gestations (fron 6 to 21 weeks). Childs.
Results: At 3-7 weeks in pancreas the expression of PanCK, CK7, CK20, Methods: The measurements of the left and right lobe carried out by two
CDX2 and MUC1,2,5АС types was negative. We found only expression ultrasound diagnostics doctors on 26 healthy volunteers with quiet breath-
CK8 in foregut epithelium. At 13-14 weeks we found expression ing and with a breath hold on a deep breath, for the left lobe with and
CK20 in goblet cells and epithelial cells of the foregut epithelium. without an inferior vena cava (IVC) in sight, for the right lobe from access
At 20-21 weeks for the first time, we found the cytoplasmic via the anterior axillary line (AAL) and midclavicular line (MCL). The
expression with CK7 and MUC1 in the epithelium of the pancre- volume of the liver was calculated by the formula J.T.Childs: 343.71+
atic ducts, which may indicate the onset of specialization. Expression of 0.84*(oblique vertical size (OVS)*anterior-posterior (AP) of the right
CK 20 was found not only in the goblet cells, but throughout the entire lobe*anterior-posterior(AP) of the left lobe) / 1000.
foregut epithelium. Results: The maximum sizes of the volumes of the liver are obtained with
Conclusion: Pancreatobiliary type of epithelium is more specialized. quiet breathing without capture in the field of view of the IVC for left
Substrate for the development of the pancreas is the foregut epithelium , lobe, and at the level of AAL and MCL for the right liver lobe, the average
which at the embryogenesis, differentiates into specialized organs and values are comparable (p ≤ 0.05).
tissues; Based on this statement and comparing the available morpholog- Conclusion: To obtain objective resultes of possible calculations of the
ical data in PDA with intestinal immunophenotype, we found only in- liver volume by different specialists, we recommended measuring the
complete intestinal metaplasia of the epithelium can be asserted, leading linear dimensions of the liver with quiet breathing, when measuring the
to further development of cancer, but not the appearance of true intestinal left lobe without IVC in view, when measuring the right lobe of AAL of
differentiation of the tumour. MCL.

E-PS-07-023 E-PS-07-025
Comparison of the results of the calculation of the liver volume of Hepatitis C: the importance of non-invasive diagnostic methods in
cadavers on the basis of linear dimensions obtained with sonography the development of liver fibrosis
and measurements ex vivo I. Stepanyan1, V. Izranov2, S. Stepanyan2, I. Ashtarkhanova2, V.
I. Stepanyan1, V. Izranov2, S. Stepanyan2, K. Abdujabborov2, M. Gordova2, I. Ivanov1, E. Konopleva2
Shushval2, V. Gordova2 1
Baltic Federal University; Infectious Diseases Hospital of the
1
Baltic Federal University; Infectious Diseases Hospital of the Kaliningrad Region, Russia, 2 Baltic Federal University, Russia
Kaliningrad region, Russia, 2 Baltic Federal University, Russia
Background & Objectives: Liver fibrosis is the inevitable outcome
Background & Objectives: We set a goal to find out whether the three of hepatitis C and detecting it in the early stages makes it possi-
linear liver sizes used in formula J.T.Childs are sufficient to get an objec- ble to adjust the therapy in such a way as to improve the quality
tive parameter of an organ volume before and after its dissection from the and increase the life expectancy of the patient. It is important to
abdominal cavity. understand how much the changes in elastometry and blood tests
Methods: Liver sonography was performed before an autopsy with mea- of patients are proportional to the stages of development of
surements of the anteroposterior (AP) of the left and right lobes and fibrosis.
oblique vertical size (OVS) of the right lobe. The left lobe was measured Methods: The results of liver 2D SWE (shear wave) elastometry on the
without view of the inferior vena cavae, the right lobe from the anterior Aixplorer (France) and the results of blood tests (indices Aspartate ami-
axillary line (AAL) and the midclavicular line (MCL). The similar to notransferase to platelete ratio (APRI) and Fibrosis-4 (FIB-4)), were com-
sonography sizes of both lobes were measured by a ruler on the dissected pared in 56 patients with hepatitis C.
liver. The linear dimensions obtained from sonography and dissection Results: The results of the liver 2D SWE elastometry with the assessment
results were substituted into the J.T. Childs formula. of the stage of fibrosis according to the conventional Metavir scale
Results: After dissection the liver from the abdominal cavity, the average showed that 25 patients had 0-1 fibrosis stage; 11 patients had stage 1-
linear dimensions significantly change: AP size of the left lobe decreases 2; 7 patients had stage 2-3; and 13 patients had stage 3-4, respectively. At
2.27 times, AP size of the right lobe decrease 1.9 times, OVS of the right the same time, with fibrosis of the 0-1 and 1-2 stages, no changes in blood
lobe increases 1.15 times. Due to changes in linear dimensions, the vol- parametes (APRI and FIB-4) were observed.
ume is according to the formula J.T.Childs after liver dissection from Conclusion: Comparison of the results of 2D SWE elastometry with the
cadavers, decreases 2.2-2.3 times (p≤ 0.05). results of laboratory blood tests show that elastometry reveals fibrosis
Conclusion: With a direct dependence of the volume of the liver on with 0-1 stage, and methods APRI and FIB-4 starting from 2-3 stages.
the above dimensions, they are not enough to obtain an objective Therefore, 2D SWE elastometry is a more sensitive method for diagnos-
parameter. It is required either to add additional linear dimensins to ing fibrosis in its early stages than APRI and FIB-4 in hepatitis C.
the formula or to introduce a non-linear correlation coefficient of
these linear dimensions.
E-PS-07-026
Detection of human polyomavirus 6 and 7 in the human cholangio-
E-PS-07-024 carcinoma tissues
The dependence of the results of the calculation of the volume of the F. Klufah1, E. Chteinberg2, G. Mobaraki1, R.A. Alharbi3, A.K. Kurz4, V.
liver according to the formula J.T.Childs on the choice of access Winnepenninckx2, E. Speel2, A. zur Hausen2
1
points and depth of breathing Department of Pathology, Maastricht University Medical Center,
I. Stepanyan1, V. Izranov2, V. Gordova2, M. Beleckaya2, S. Stepanyan2 The Netherlands, 2 Maastricht University Medical Centre+,
1
Baltic Federal University; Infectious Diseases Hospital of the The Netherlands, 3 Faculty of Applied Medical Sciences, Albaha
Kaliningrad Region, Russia, 2 Baltic Federal University, Russia University, Saudi Arabia, 4 University Hospital RWTH Aachen, Germany

Background & Objectives: We noticed that the linear dimensions of the Background & Objectives: Cholangiocarcinoma (CCA) is a rare biliary
liver depend on the access points and the depth of breathing. Study duct neoplasm with poor prognosis. Recently, the presence of HPyV6 has
 Virchows Arch

been reported in the bile hepatobiliary diseases including the bile of CCA and mesoderm. They are usually located on the ovaries and testis. Liver
patients. Here, we investigated the prevalence of HPyV 6 and 7 in CCA teratomas are extremely rare and comprise less than 1% of all teratomas.
by using diverse molecular techniques to assess their possible role in Pathological diagnosis is crucial to confirm radiological suspicion along
neoplastic hepatobiliary diseases. with the assessment of immature component, which has implications in
Methods: We tested 61 FFPE tissues of 21 CCA patients. PCR screening further management of these patients.
for HPyVs were conducted using a pair of degenerated HPyV primers. Methods: The present study is a case report of a liver teratoma in an adult,
Specific-PCRs for HPyV6 and 7 and MCPyV were performed. All PCR diagnosed and treated in 2019.
products were sequenced. FISH, RNA(ISH) and immunohistochemistry A 27-year-old woman, with no relevant prior medical history, was admitted in
(IHC) were used to assess the presence of HPyV6 and 7 on the DNA, our Medical Centre in March 2019 after the incidental discovery of a hepatic
transcriptional and transitional level. lesion on a CT-scan: there were distinctive imaging characteristics suggesting
Results: Degenerated primers revealed the presence of HPyV7 in 4 out of liver teratoma, and based on this information the patient was electively sub-
21 CCAs (19%) and HPyV6 in 2 CCAs (9.5%). The presence of HPyV7 mitted to a mesohepatectomy for the centrally located hepatic lesion.
and 6 DNA was confirmed by specific FISH. RNA-ISH confirmed the Results: Gross pathological examination showed a cystic tumour with
presence HPyV6 and 7 on the single cell level. IHC using monoclonal 21cm: cut section revealed multiple cystic areas with sebaceous material,
antibodies (HPyV7 2T10 and HPyV6 1T1, both kindly supplied by Dr. C. hair and calcifications. Microscopic examination showed a mixture of
Buck, NCI, Bethesda, USA) revealed the specific nuclear expression of various tissues, including skin and appendages, bone, adipose tissue
viral proteins within these tissues. and respiratory epithelium: the final diagnosis was Mature Liver
Conclusion: HPyV6 and 7 are hepatotropic and can be specifically found Teratoma, fully resected. The patient had a gradual post-operative recov-
in peritumoural non-neoplastic hepatocytes and to a lesser extent in neo- ery phase without major complications and was discharged after 9 days of
plastic CCA cells. In our patient cohort, HPyV7 was found to be more hospitalisation. 2- and 4-weeks follow-up confirmed absence of symp-
prevalent than HPyV6. Based on our results, HPyV6 and 7 are yet un- toms and a full recovery.
likely to play an important role in the etiopathogenesis of CCA. Conclusion: Liver Teratomas are extremely rare, even more in adults,
with only a small number of cases described in the literature. Albeit they
harbour some extremely distinctive imagiological features, pathological
E-PS-07-027 examination is vital to the correct diagnosis and characterization of tera-
Solid-pseudopapillary neoplasm of the pancreas: a (not so) rare tomas. Complete resection of the lesion remains, to this day, the best
diagnosis treatment option.
C. Alves-Vale1, R. Brodbeck Ilgenfritz1, P. Borralho1
1
CUF Descobertas Hospital, Department of Pathology, Lisbon, Portugal
E-PS-07-029
Background & Objectives: Solid-pseudopapillary neoplasm (SPN) is an Unique cystic neoplasm of liver in child-undifferentiated embryonal
extremely rare entity, corresponding to 0.9-2.7% of all exocrine pancreatic sarcoma
tumours, mostly affecting young women. We aimed to review the clinical Z. Yusifli1, M. Kazimi1, K. Beydullayev1
1
and histopathological features of the SPNs diagnosed in our department. Central Customs Hospital, Azerbaijan
Methods: This retrospective analysis collected all cases of SPN diag-
nosed between January 2009 and March 2019. Clinicopathological data Background & Objectives: Undifferentiated embryonal sarcoma of the
was analysed. liver (UESL) is a unique and rare malignant mesenchymal neoplasm. We
Results: The diagnosis of SPN was made in four patients: one after fine- report a case of UESL observed in a 14 year old boy. The patient underwent
needle aspiration and three after surgery, corresponding to 5.1% (3/59) of liver resection for cyst hydatid. The intraoperative frozen section technique
all surgically resected pancreatic neoplasms in our institution. The group was used during operation and was reported as fibrinous tissue, no malig-
includes one male and three female patients, with a mean age of 36.5 nancy. Grossly 14 x 11cm encapsulated mass were seen in liver parenchy-
years (SD±14.7). The three patients undergoing surgery in our hospital ma. The cut surface was soft with necrosis and haemorrhage areas.
presented with a single mass located in the pancreatic tail, with a mean Methods: Specimens were fixed in 10% formalin solution and embedded
size of 105.0 mm (SD±20.0). The lesion was associated with nausea in in paraffin. Sections were stained with Haematoxylin eosin and special
one patient and it was incidentally found in imaging studies in the remain- immunohistochemical stains. Staining was considered positive when
ing two cases. Gross examination revealed an encapsulated lesion, with >10% of cells showed positive staining with appropriate pattern.
both solid and/or cystic components. Microscopic analysis showed solid Results: Microscopic examination showed tumour with hypocellular and
areas and pseudopapillae covered by epithelial cells positive for beta- myxoid stroma. In some areas tumour was highly cellular with marked
catenin, CD56, CD10 and vimentin. Complete excision of the lesion pleomorphism. Bizarre hyperchromatic giant cells, cytoplasmic hyaline
was achieved in all cases. No evidence of relapse has been detected eosinophilic globules and entrapped benign bile ducts were present.
(follow-up period: 3 months-6 years). Immunohistochemical staining showed positivity for CD56, desmin,
Conclusion: A correct morphological analysis supported by ancillary SMA, CD68 and were negative for pan-cytokeratin, Heppar-1. The
studies allows the diagnosis of SPN. Our series adds to the list of this MIB-1 proliferation index was 20-25% in neoplastic cells. Based on these
singular entity while reminding us of its possibility in male patients. findings, a diagnosis of UESL was confirmed.
Conclusion: UESL is a rare and aggressive mesenchymal neoplasm which
occurs almost exclusively in children and adolescents. Intraoperative frozen
E-PS-07-028 sections technique is not usefull, because cysts, necrosis and haemorrage
Mature cystic teratoma of the liver: a case report areas may occupy up to 80-90% of the cut surface. Early correct diagnosis
M. Varela dos Santos1, A. Figueiredo2 and complete resection are necessary for a favorable outcome. This entity
1
Serviço de Anatomia Patológica - Centro Hospitalar e Universitário de should keep in mind in all cystic liver masses in children.
Lisboa Central, E.P.E., Portugal, 2 Serviço de Anatomia Patológica -
Hospital Curry Cabral, Centro Hospitalar e Universitário de Lisboa
Central, E.P.E., Portugal E-PS-07-030
Cystic lymphangioma in pancreas
Background & Objectives: Teratomas are germ cells tumours, which M. Chantziara1, D. Mpouklas1, G. Theodoropoulou1, S. Roditis2, X.
must contain more than one of the three germ layers: ectoderm, endoderm Grammatoglou1, A. Kostopoulou1, I. Margaris3, T. Choreftaki1
Virchows Arch

1
Department of Surgical Pathology/General Hospital of Athens, chemoradiotherapy and had no tumour recurrence or metastasis until
"G.Gennimatas", Greece, 2 3rd Department of Surgery/General Hospital 25 months after surgery.
of Athens "G. Gennimatas", Greece, 3 2nd Department of Surgery/ Conclusion: Adenosquamous carcinoma is defined as a tumour which
General Hospital of Athens "G. Gennimatas", Greece has both adenocarcinoma and squamous cell carcinoma components. Its
histogenesis is not clear. While it has been reported in the oesophagus,
Background & Objectives: We present the case of a 50-year-old male stomach, small intestine and colorectum, rare in the ampulla of Vater.
patient with cystic lymphangioma in pancreas.
Methods: The patient presented to the surgery department complaining
of atypical abdominal pain the last six months. An abdominal computer- E-PS-07-032
ized tomography (CT) scan was performed and a cystic neoplasm with a Ductal adenocarcinoma of the pancreas with extensive hyaline glob-
maximum diameter of 18.6 cm was seen at the pancreatic body and tail. ules: a case report
The mass had not invaded any adjacent organs. The lesion was aspirated M.E. Kara1, E. Uzun1
1
using the EUS-FNA needle. Cytology felt to be consistent with the diag- Gaziantep University Medical Faculty Hospital, Department of
nosis of pancreatic serous cystadenoma. The patient underwent peripheral Pathology, Turkey
pancreatectomy and spleenectomy.
Results: On gross sectioning, the cystic neoplasm had a honeycomb Background & Objectives: Ductal adenocarcinoma is the most common
appearance with single space filled with haemorrhagic yellowish fluid. type of pancreatic cancer (constitutes %90 of all pancreas cancers) and it
Microscopic examination revealed cystic lesions of variable size, separat- is a type of exocrine pancreatic cancer. In the world; ductal adenocarci-
ed by fibroconnective septa, containing irregular smooth muscle fasci- noma of the pancreas is the fourth most common cause of death from
cles, adipocytes and mature lymphocytes. These cystic spaces were lined cancer in both men and women. Early recognition of these precursor
by flattened and slightly elevated endothelial cells. No cell atypia was lesions is important to improve the treatment and prognosis of PDAC.
found. Immunohistochemistry (IHC) labeling for endothelial markers, Methods: Case report: A 58 years old female patient was presented with
factor VIII-R antigen and CD 31 was positive while CD 34 was focally weight loss and fever. Laboratory examination revealed that alkaline
weakly positive. Furthermore, immunohistochemistry for Inhibin-a, phosphatase (ALP), gamma-glutamyl transferase (GGT) and amylase
EMA, CK19, CKAE1/AE3, MUC-1 was negative. So, the diagnosis of levels were elevated. CA19-9 level was 896 U/mL. Contrast-enhanced
pancreatic lymphangioma was made. computed tomography (CT) revealed a solid mass in the head of the
Conclusion: Cystic lymphangioma of the pancreas is extremely rare, pancreas, measuring 25x20 mm. Pancreatoduodenectomy was per-
accounting for less than 1% of pancreatic tumours but should be taken formed. Grossly; the infiltrative, solid tumour was detected in the head
into consideration as a differential diagnosis of a pancreatic cystic lesion. of the pancreas which was infiltrating duodenal wall.
Results: Histologically; tumour had ductal adenocarcinoma morphology
with extensive hyaline globules. Immunohistochemically; the tumour
E-PS-07-031 was positive with CK7, CK19, MUC1, MUC5, and Maspin. Lymph node
Adenosquamous carcinoma of the ampulla of Vater: report of two metastasis, lymphovascular and perineural invasion were present.
cases Margins were uninvolved. After surgery patient is receiving chemoradio-
M.E. Kara1, E. Uzun1 therapy for 2 months.
1
Gaziantep University Medical Faculty Hospital, Department of Conclusion: Hyaline globules in the pancreas are usually seen in solid
Pathology, Turkey pseudopapillary carcinomas. While Neuroendocrine carcinomas can also
have hyaline globules focally, it is uncommon in ductal adenocarcinomas.
Background & Objectives: Primary adenosquamous carcinoma of the Because of its rarity; there is no data about the meaning of hyaline glob-
ampulla of Vater is rare. There are few reports about its clinicopatholog- ules in pancreatic ductal adenocarcinomas.
ical features. Here, we report two adenosquamous carcinomas of the
ampulla of Vater.
Methods: CASE 1 E-PS-07-033
A 62 years-old male presented with abdominal pain and jaundice. The Unusual localisations of hydatid cyst and its clinicopathological
laboratory examination revealed alanine aminotransferase (ALT), aspar- features
tate aminotransferase (AST), lactate dehydrogenase (LDH), amylase and M.E. Kara1, E. Uzun1
1
total bilirubin levels elevated. CA 19-9 level was 242 U/mL. Computed Gaziantep University Medical Faculty Hospital, Department of
tomography (CT) revealed a solid mass in the periampullary region. Pathology, Turkey
Pancreatoduodenectomy was performed to the patient. Grossly infiltra-
tive, solid mass, measuring 4.2x3x3 cm, was detected in the ampulla of Background & Objectives: Hydatid cyst is a zoonotic parasitic disease
Vater. Histopathologically; the tumour was comprised both of adenocar- caused by Echinococcus granulosus larva. It is endemic in Turkey and is a
cinoma and squamous cell carcinoma elements. The retroperitoneal mar- big health problem in farming areas. The hydatic cyst is mostly seen in the
gin was involved, pancreas invasion and lymph node metastasis were liver and lung, it can rarely occur in atypical localizations.
present. The patient has received chemoradiotherapy and had no tumour Methods: In this study 550 hydatid cysts which were diagnosed
recurrence or metastasis until 48 months after surgery. in Gaziantep University Medical Faculty Hospital between 2012-
Results: CASE 2 2019, were evaluated based on criteria such as sex, age, cyst
A 49 years-old female patient presented with abdominal pain and localization, liver or lung involvement for atypical localized cysts,
jaundice. The laboratory examination revealed ALT, AST, LDH, Echinococcus granulosus indirect hemagglutination antigen (IHA)
gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), test status.
amylase and total bilirubin levels elevated. CA 19-9 level was 560 Results: 232 of (%42.2) 550 cyst hydatids were localized in lung, while
U/mL. Computed tomography revealed a solid mass in the 231 (%42) were in liver. 87 of 550 cyst hydatids were localized outside of
periampullary region. Whipple procedure was performed. Grossly; liver and lung. 16 of these cysts were in the kidney, 13 were
solid mass, measuring 2.5x1.5 cm, was observed in the ampulla of intraabdominal, 13 were in the spleen, 9 were in the heart, 7 were in the
Vater. Duodenum wall was involved by tumour. Microscopic exam- brain, 2 were in the ovary, 1 was in the pancreas, 1 was in diapraghm, 1
ination revealed that the tumour comprised both adenocarcinoma was in the gallbladder and 23 were in the musculoskeletal system. 24 of
and squamous cell carcinoma components. The patient has received (%27,5) 87 unusually localized cyst hydatids showed lung or liver
 Virchows Arch

involvement. Right lower lobe and left upper lobe were most involved Upon section, centered on the pancreatic duct, there was a firm and
lobes by cyst hydatid at 39% and 25%, respectively. whitish area, with ill-defined limits, measuring 6x4x4cm. The histologi-
Conclusion: Although its typical localizations are liver and lung, hydatid cal analysis showed a pancreatic parenchyma extensively involved by an
cyst can be seen in unexpected organs/tissues. It should be evaluated in intense interlobular fibro-inflammatory process, containing an abundant
differential diagnosis because of its tumour mimicry in imaging studies. inflammatory infiltrate rich in plasmocytes, lymphocytes and eosinophils.
This process extended to the peri-pancreatic adipose tissue and was close
to the mesenteric vein bed. Multiple lesions of obliterative venulitis and
E-PS-07-034 phlebitis (highlighted using the Van Gieson elastin staining) were present.
Pancreatic mixed neuroendocrine- nonneuroendocrine neoplasm: a The immunohistochemistry study confirmed the presence of numerous
case report CD38+/CD138+/IgG+ plasmocytes and more than 75% were IgG4-
S. Batur1, î Kutlu1, K. Ozcan1, G. Ozcan1, N. Kepil1, T. Ozturk1 positive plasmocytes (beyond 100 IgG4-positive plasmocytes per high-
1
Istanbul University Cerrahpasa-Cerrahpasa Medical Faculty power field). A diagnosis of IgG4-related type 1 autoimmune pancreatitis
Department of Pathology, Turkey was made. The ensuing immunological study revealed serum IgG4 levels
(1240 mg/dL) nearly 14 times above normal.
Background & Objectives: The WHO classification of the tumours of Conclusion: This case reports an incidental presentation of a pathology
endocrine organs, published 2017, has introduced significant changes in less frequent than pancreatic cancer, but which can mimic it on imaging
the classification of pancreatic neuroendocrine tumours. The previous studies. The IgG4-related autoimmune pancreatitis is treated with corti-
term mixed adeno-neuroendocrine carcinoma (MANEC) is substituted costeroids for at least 3 months, or rituximab in patients with steroid
by the term mixed neuroendocrine-non neuroendocrine neoplasm intolerance. A better correlation between serum IgG4 levels, imaging
(MiNEN). MiNEN are neoplasms with two distinct neuroendocrine and features and biopsy findings could help to avoid pointless surgical ap-
non-neuroendocrine cell populations. Pancreatic MiNEN represent 0.5% proaches and complications.
of all pancreatic adenocarcinomas and 5% of all pancreatic NEN.
Methods: A 63-year-old man presented with jaundice and was referred to
our hospital for further examination. Abdominal contrast-enhanced computed E-PS-07-036
tomography revealed a mass of 4,3 cm in size in the pancreas head with portal Acinar cell cystadenoma of the pancreas: report of a case and a
vein narrowing. Pancreatoduodenectomy and regional lymph node dissection comprehensive review of the literature
were performed. Macroscopically, the ill defined infiltrative tumour was iden- C. Vestrup Rift1, J. Preuss Hasselby1, C. Palnæs Hansen2, B. Federspiel1
1
tified at the head of the pancreas. The tumour was 7x3,8x2,5cm in diameter. Department of Pathology Copenhagen University Hospital
Results: Histological examination revealed that the tumour consisted of Rigshospitalet, Denmark, 2 Department of Surgery Copenhagen
two cell populations.: well differentiated ductal adenocarcinoma (%60), University Hospital Rigshospitalet, Denmark
and neuroendocrine tumour cells arranged in a nest, with round nuclei,
abundant cytoplasm, and coarse chromatin. Immunohistochemically, the Background & Objectives: Acinar cell cystadenoma (ACC) is a rare
adenocarcinoma cells were positive for MUC1 and MUC5AC, while the cystic lesion of the pancreas. We hereby present a case of ACC and a
neuroendocrine tumour cells were positive for chromograninA, review of the literature to characterise the patient population.
synaptophysin and CD56. Based on the findings, a diagnosis of Methods: A systematic review was performed using PubMed and the
MiNEN of the pancreas was made. Metastasis of the two components keywords “acinar cell cystadenoma” and “acinar cystadenoma”, yielding
of the tumour was observed in the lymph nodes. a total of 24 publications.
Conclusion: We reported an extremely rare case of a MiNEN derived from Results: A total of 75 cases including our case report has previously been
the pancreas. The clinical features and effective treatment of such tumours described in the literature. The patients are primarily female with present-
have not been well-described due to their rarity. Therefore, more reports of ing symptoms of abdominal pain. The cysts are located in the head of the
cases of pancreatic MiNEN are necessary for a complete analysis. pancreas, and are often multilocular on cross section with a mean size of
53,2 mm. Microscopically the cysts are lined by a PAS positive acinar
epithelium, often with abortive acinar formations. The cells are
E-PS-07-035 immunohistochemically positive in stains for trypsin, chymotrypsin and
Incidental IgG4-related autoimmune pancreatitis in a middle-aged CK7. The Ki67-index is reported low, 1-2%. No malignant transforma-
patient with suspected pancreatic neoplasia - a case report of an tion has been reported, and the mean follow up time is 37,4 months.
uncommon entity Conclusion: ACC is a rare cystic lesion with no malignant potential,
N.J. Lamas1, M. Oliveira1, L. Ferreira1, C. Fleming1, R. Amorim2, B. primarily affecting women. The indication for surgical intervention
Fernandes2, J.R. Brandão2, F.E. Costa1, J.R. Vizcaíno1 should be based on the symptoms of the patients, as no risk of malignancy
1
Anatomical Pathology Service, Department of Pathology, Hospital and has been reported.
University Center of Porto, Porto, Portugal, 2 Centro Hospitalar do Porto,
Portugal Supported by the Research foundation of Copenhagen University
Hospital Rigshospitalet.
Background & Objectives: IgG4-related disease (IgG4-RD) is a
fibroinflammatory pathology with either synchronous or metachronous
multi-organ involvement. Patients develop focal or diffuse organ enlarge- E-PS-07-037
ment with mass-forming or nodular lesions containing abundant infiltra- Acinar cell carcinomas of the pancreas: report of 4 cases
tion by IgG4-positive plasmocytes and fibrosis. In pancreas, these lesions E. Ben Hadj Khalifa1, A. Bdioui1, z. Nfikha1, A. Baccouche1, T.
frequently mimic neoplasia on imaging studies. Zahmoul2, B. Sriha1, M. Mokni1
1
Methods: We report the case of a 66-year-old male with a computed Cytology and Pathology Department CHU Farhat Hached, Sousse-
tomography scan showing dilated intra-hepatic biliary tree and common Tunisia, 2 Cancer Registry of the Tunisian Center, Tunisia
bile duct thickening in a 30mm extension in its final portion. A pancreatic
head neoplasia was suspected, and the patient underwent cephalic Background & Objectives: Acinar cell carcinoma is a rare malignant
duodenopancreatectomy. tumour of the pancreas, accounting for only 1 to 2% of pancreatic tu-
Results: A surgical specimen comprising a 7,5x5,5x2,5cm pancreatic mours. The diagnosis is based on the pathological examination and im-
head, a 7cm stomach piece and an 11cm duodenal segment was received. munohistochemistry study. The main differential diagnosis is the
Virchows Arch

neuroendocrine tumours. The treatment is based on surgical resection and E-PS-07-039

chemotherapy. The prognosis is reserved and the average survival does Latent pancreatic metastasis, 13 years after renal cell carcinoma - a
not exceed 18 months.The purpose of this work is to report, from 4 case report
clinical cases and a review of the literature, the clinico-pathological, ther- M. Danciu1, C.E. Andriescu2
1
apeutic and progressive features of pancreatic acinar cell carcinoma. Grigore T. Popa UMF Iasi, Romania, 2 Sf. Spiridon Emergency County
Methods: Our study was retrospective, descriptive, dealing with 4 cases Hospital Iasi, Romania
of acinar cell carcinoma, collected in the laboratory of pathological anat-
omy and cytology of Sousse, during a period of 10 years. Background & Objectives: Pancreatic metastasis represent less than 4%
Results: The mean age of the patients was 60 years, with extremes of 50 to of all pancreatic tumours, about 1-4% originating from renal cell carci-
65 years, the sex ratio was 1. The most common clinical sign was abdominal nomas (RCC). We present the case of a solitary pancreatic metastasis
pain. Morphological examinations revealed a pancreatic tumour, which was occurring 13 years after nephrectomy, in a 69-year-old female patient.
cephalic in 2 cases and caudal in 2 cases; the size varied from 3 to 15 cm with Methods: The surgical resection specimen was submitted for intraoper-
a solid-cystic aspect, well circumscribed, with presence of foci of necrosis, in ative consultation (frozen sections). HE staining and immunohistochem-
the most voluminous tumours. On histological examination, the tumour cells ical tests were performed after routine processing of the whole sample.
were cubo-cylindrical, with strongly nucleated monomorphic nuclei, orga- Results: Gross examination revealed a well circumscribed yellow 2.2 cm
nized into small glands and spans. The mitotic activity was variable and the nodule, in the pancreatic isthmus. On frozen section examination, the
stroma was fibrous. Foci of necrosis were observed. The IHC study showed tumoural nodule consisted of isles and trabeculae of large round
diffuse expression of trypsin and pancytokeratin (CK). Anti-CK7, CK20, cells with central hyperchromatic nuclei surrounded by finely vac-
CD10 and C-KIT antibodies were negative. The treatment was surgical cor- uolar cytoplasm. Lacking the relevant clinical information regarding
responding to a spleno-pancreatectomy in one case, and a double diversion patient history, a diagnosis of malignancy was provided. The histo-
with cholecystectomy in another. The other two patients had palliative treat- logical examination of the paraffin embedded tissue yielded new
ment. The decline ranged from 3 months to 7 years. The evolution was morphological details of the tumour population: polygonal cells
marked by the appearance of hepatic metastases in 2 patients, one with an with clear cytoplasm and moderate pleomorphism, inconspicuous
adrenal metastasis. mitotic activity, sparse vascular stroma, peripheral fibrosis. The sus-
Conclusion: Pancreatic acinar cell carcinoma is a rare tumour, diagnosed picion of pancreatic metastasis of RCC was advanced based on
at a late stage, given its clinical latency. Due to the rarity of this neoplasm, tumour morphology and patient’s history of nephrectomy (provided
its therapeutic approach is still not codified. Surgical treatment with upon request). Immunohistochemical tests (positive for RCC, CK7,
carcinologic resection seems to be the standard treatment. CD10; negative for CK20) confirmed the diagnosis.
Conclusion: In absence of the oncological history of the patient, a soli-
tary pancreatic nodule may raise difficulties on frozen section examina-
E-PS-07-038 tion in differentiating a primary pancreatic tumour from a metastasis. As
Rare pancreatic tumours: about four cases about 70% of pancreatic metastasis originates from RCC, one should
B. Laabidi1,2, R. Hedhli3, R. Yaich1,2, N. Mansouri4, F. Gargouri4, A. always consider this scenario, even if the RCC was resected more than
Saidi4, A. Bouziani4, I. Msakni4 one decade ago, as in our patient.
1
Tunis El Manar University, Medicine School of Tunis, Tunisia,
2
Military Hospital of Tunis, Department of Pathology, Tunisia, 3 Tunis El
Manar University, Medicine School of Tunis Military Hospital of Tunis, E-PS-07-040
Department of Pathology, Tunisia, 4 Pathology Department; Military A rare case of pancreatic carcinosarcoma with unique histological
Hospital for Instruction of Tunis, Tunisia pattern
I.A. Spiridon1, S. Lunca1,2, D. Ferariu3
1
Background & Objectives: The pancreas harbors a wide array of dis- "Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania,
2
eases. It involves many uncommon non-neoplastic and neoplastic condi- Second Clinic of Surgery, Regional Institute of Oncology, Iasi,
tions. As for the rare pancreatic tumours, they can vary from solid to Romania, 3 Department of Pathology, Regional Institute of Oncology,
cystic features, ranging from benign to low-grade malignant ones.We Iasi, Romania
report here four cases of three rare histological types of tumours that occur
in the pancreas. Background & Objectives: Carcinosarcoma is a rare biphasic tumour
Methods: The first case is of a 45-year-old female who presented with with epithelial and mesenchymal features, most commonly arising in the
abdominal pain. The second case concerned a 25-year-old female who uterus. The pancreatic location of this neoplasm is an extremely rare
was diagnosed with a painful cystic mass of the pancreatic tail. The third finding, with few cases recorded in literature. We report the occurrence
case is of a 41-year-old man who presented with a solid epigastric mass. of a pancreatic carcinosarcoma in a 63-year-old male patient.
The fourth case reported a 69-year-old male who was diagnosed with a Methods: Multiple samples from the complex surgical resection speci-
pancreatic tail tumour. men were routinely processed. HE staining and immunohistochemical
Results: In the first and second case, histopathological examination and tests were performed.
immunohistochemistry on biopsy led to the diagnosis of solid Results: On gross evaluation, the resection specimen revealed a tumoural
pseudopapillary pancreatic tumour. Both patients underwent respectively mass apparently originating in the pancreas and engulfing several other
pancreatoduodonectomy and distal pancreatectomy. In the third case, the organs (duodenum, colon, left kidney, spleen). The histological examina-
diagnosis of Solitary fibrous tumour was concluded on histological and tion identified two distinct areas, a tumoural population of epithelial or-
immunohistochemical findings on biopsy. The patient was treated surgi- igin, forming microlobular to trabecular aggregates, with abundant eosin-
cally. The operative follow-up was marked by a diffuse hemorrhagic ophilic cytoplasm and marked nuclear pleomorphism, in collision with a
syndrome leading to the patient’s death on the 3rd post-operative day. highly cellular proliferation of spindled cells, with sarcomatous morphol-
In the last case, microscopic features on lumpectomy confirmed the di- ogy and notable pleomorphism, often with bizarre, multinucleated cells.
agnosis of pancreatic lymphangioma. Mitotic activity was increased in both of the tumoural populations, with
Conclusion: The pancreas may be involved with a large variety of an associated Ki-67 index of over 90%. Immunohistochemistry con-
unfrequent solid or cystic neoplasms. Therefore, operative exploration is the firmed the epithelial component as neuroendocrine carcinoma (positive
treatment of choice of these rare lesions to provide the correct diagnosis based CKAE1/AE3, Chromogranin, Synaptophysin), while the spindled area
on histological examination and initiate adequate surgical therapy. was classified as undifferentiated pleomorphic sarcoma, with negativity
 Virchows Arch

for CKAE1/AE3, EMA, CK7, CD117, CD34, SMA, Desmin and posi- αSMA and vimentin expression was evaluated in HCC and iCC.
tivity for Vimentin. Methods: One-hundred and thirteen epithelial malignant liver lesions
Conclusion: This is, to our knowledge, the first reported case of a pan- were studied, from 52 consecutive patients undergoing resection or liver
creatic carcinosarcoma associating a malignant neuroendocrine compo- transplantation. Pathological review was performed and tumours were
nent with an undifferentiated pleomorphic sarcoma component. While classified according to World Health Organization 2010. αSMA actin
with recent studies argue for the monoclonal origin of this tumour, its and vimentin expression was considered positive when single tumour
prognosis remains dismal, with otherwise limited consensus regarding cells or tumour cell clusters showed immunoreactivity, whereas negative
surgical management and postoperative treatment. expression was defined as no detectable expression.
Results: From the 18 early HCC studied, 6 (33,3%) had αSMA expres-
sion and 10 (55,6%) were vimentin-positive, 12 (66,7%) showed
E-PS-07-041 perinodular αSMA positive hepatocytes and 12 (66,7%) perinodular
Glycogenic hepatopathy - an underrecognised clinicopathological vimentin positive hepatocytes; of the 56 advanced HCC, 19 (33,9%)
entity expressed αSMA and 30 (53,6%) had vimentin positive cells, 26
A. Baltan1, I. Simionov1, A. Constantinescu1, G. Becheanu1 (46,4%) presented perinodular αSMA in hepatocytes and 26 (46,4%)
1
Fundeni Clinical Institute, Romania perinodular vimentin positive hepatocytes; none from the 6 iCC
expressed αSMA and 4 (66,7%) had vimentin expression, perinodular
Background & Objectives: We present the case of a 21-year-old male hepatocytes expressed αSMA in 4 (66,7%) iCC and perinodular hepato-
with type 1 diabetes mellitus, who complained of weight loss and fatigue, cytes expressed vimentin in 5 (83,3%).
having elevated transaminase, gamma glutamyl transferase and glucose Conclusion: αSMA and vimentin expression either in tumour cells of
blood levels. Abdominal ultrasound showed hepatomegaly and diffuse HCC and iCC may correlate with EMT. Dedifferentiation of liver epithe-
liver hyperecogenicity, which was considered to represent mild steatosis. lial benign/malignant cells reflects the importance of tumour microenvi-
Autoimmune hepatitis was suspected and serologic tests showed slightly ronment in PLC development, which may retain clinical specificities.
increased anti-nuclear antibodies levels and absence of a viral liver
infection.
Methods: The sampled liver tissue was immediately immersed and fixed E-PS-07-043
in 10% neutral buffered formalin solution, 3 μm thick sections were An unusual case of metastatic liver melanoma in a patient with
obtained and H&E, Perls and van Gieson stains were performed. chronic lymphocytic leukemia
Results: The liver biopsy had a total length of 10 mm. The lobular A. Sykaras1, A. Paraskevas1, D. Sampaziotis1, K. Pavlou1, K. Roidou1,
architecture was preserved and the portal spaces were unremarkable. C. Kouvidou1
1
The hepatocytes were diffusely enlarged, with abundant clear cyto- Department of Pathology, Evangelismos General Hospital, Athens,
plasm and visible cytoplasmic margins. Rare steatotic macrovesicles Greece
and relatively frequent megamitochondria were present. The hepa-
tocyte nuclei varied slightly in size and some of them were Background & Objectives: The major hematologic conditions in pa-
glycogenated. No inflammation was noted, except for a few tients with multiple malignancy are multiple myeloma, myelodysplastic
intralobular neutrophils, and fibrosis was not identified. The histo- syndromes, non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic
pathological diagnosis was glycogenic hepatopathy. The pacient re- (CLL) or myelogenous leukemia. Specifically, patients with a history of
ceived a adequate insulin regimen and is currently on follow-up, CLL or NHL have a higher incidence of melanoma. If they are synchro-
with clinical improvement. nous the patient’s prognosis may be adversely affected.
Conclusion: Glycogenic hepatopathy is a rarely reported entity, with an Methods: We present a 69 years old man with a history of CLL treated
unspecific clinical pattern. It should be suspected in diabetic patients, with chemotherapy three years ago. The patient presented to haematology
particularily with type 1 diabetes mellitus, and liver abnormalities. department with fever, weight loss and anorexia. The CT scan revealed
Liver biopsy exammination is needed for a definitive diagnosis. multiple foci in the liver and a needle biopsy was performed.
Results: The needle biopsy showed two distinct neoplastic populations.
The first consisted of small to medium size lymphocytes with
E-PS-07-042 immunophenotype CD20+, Pax-5+, CD5+, CD23+ and LEF-1+ suggest-
Alpha-smooth muscle actin and vimentin expression in primary liver ing liver infiltration from CLL cells. A second population of epithelioid
carcinomas may relate with epithelial-mesenchymal transition cells with visible nucleoli and immunophenotype Melan-A+, HMB45+,
carcinogenesis S100+, MITF-1+, BRAF V600E- established the diagnosis of malignant
L. Carvalho1, A.F. Ladeirinha1,2, A. Alarcão1,2,3, L. Neves1, R. Santos4, J. melanoma. Our patient has not a known melanoma in skin or gastroin-
Espírito Santo5 testinal tract.
1
Institute of Anatomical and Molecular Pathology, Faculty of Medicine of Conclusion: The coexistence of CLL with melanoma has been reported
the University of Coimbra, Coimbra, Portugal, 2 CIMAGO - Research in lymph nodes but not in the liver, to our knowledge. It has been sug-
Center for Environment, Genetics and Oncobiology, Faculty of Medicine, gested that in CLL the dysfunctional lymphocytes are unable to elicit an
University of Coimbra, Coimbra, Portugal, 3 Centre of Pulmonology, Faculty antitumour response, thereby contributing to the increased incidence of
of Medicine of the University of Coimbra, Portugal, 4 Internal Medicine carcinomas and melanomas in these patients. Moreover, the immunosup-
Department A, Coimbra Hospital and Universitary Centre, Portugal, 5 pressive effect of chemotherapeutic agents and irradiation used to treat
Adult and Paediatric Liver Transplantation Unit, Coimbra Hospital and NHL increase the risk of cancer in these patients.
Universitary Centre, Portugal

Background & Objectives: Hepatocellular carcinoma (HCC) represents E-PS-07-044

85-90% and intrahepatic cholangiocarcinoma (iCC) 10-25% of all prima- A rare case of granular cell tumour in the biliary tract
ry liver carcinomas (PLC), where epithelial-mesenchymal transition A. Sykaras1, S. Pantelakos1, D. Sampaziotis1, K. Botsakis2, C. Stamou1,
(EMT) may play a key role in hepatocarcinogenesis. Thought to be asso- N. Stavrinou1, C. Kouvidou1
1
ciated with the acquisition of aggressive traits by tumour cells, alpha- Department of Pathology, Evangelismos General Hospital, Athens,
smooth muscle actin (αSMA) and vimentin may be specific markers of Greece, 2 Department of Surgery, Evangelismos General Hospital,
epithelial - mesenchymal origin. Athens, Greece
Virchows Arch

Background & Objectives: Granular cell tumours (GCT) are rare usually Background & Objectives: The rare solid-pseudopapillary neoplasm of
benign neoplasms although some of them may be focally aggressive and the pancreas (SPNP) occurs predominantly in young females; after com-
<2% are malignant. GCTs may be found in the tongue, skin, gastrointestinal plete surgical resection, about 85-95% of patients are cured. Long
tract, lung, urinary bladder, breast and thyroid. Biliary GCTs represent <1% disease-free periods have been recorded even in patients with local spread
of all the GCTs and are rarely diagnosed preoperatively, <90 cases have been or metastasis. We present a patient with an unusual clinical picture of
reported in the literature and no cases of malignant GCT has been published. SPNP, and a review of the literature.
Methods: A 57 years old woman was presented to surgical department Methods: A 27-year-old female with complaints of abdominal pain and
with jaundice, mild pruritus and abdominal pain. Ultrasound imaging, CT nausea had a CT-scan that depicted a mass of possible pancreatic origin in
scan and MRI revealed excessive dilation of the endohepatic and extra- her left flank. Multiple nodules were reported in the abdominal and pelvic
hepatic biliary tree and an ovoid solid mass of 13mm located in the cavities. A core biopsy was performed and the lesion was classified as SPNP.
common bile duct. The endoscopic needle biopsy were not performed Results: The tumour was excised and the diagnosis of SPNP was con-
due to the location of the tumour and a whipple procedure was performed firmed, based on the morphological pattern and immunocytochemistry
due to the suspicion of cholangiocarcinoma. studies. A CTNNB1 mutation was found. Regarding the seven cases of
Results: The gross examination revealed a yellow solid tumour 1mm SPNP we retrieved from our files, between 2011 and 2018, the male:
causing thickness of the wall and partly obstruction of the duct. The female ratio was 1:6 and the age ranged between 18-68. This case was
histopathological features and the immunohistochemistry (S100+, the only one showing disseminated disease at the time of diagnosis. A
CD68+, inhibin a +, actin-, desmin-, CD117-) were consistent with a follow-up was available in 5 cases (from 1-8 years) and all the patients are
benign granular cell tumour. No necrosis, no atypia, no increased mitosis well and asymptomatic.
were seen. Radiation or chemotherapy were not recommended. 16 Conclusion: SPNP can display abdominal widespread disease in a min-
months postsurgically the patient showed no signs of disease. ute number of cases, with no apparent prognostic implications. This clin-
Conclusion: GCTs of biliary tree are commonly found in the common ical picture does not seem to correlate with a particular histological pat-
bile duct (58-49%) and in common hepatic duct (23%). Myoblasts, his- tern. Our patient has a follow up time (12 months) free of symptoms and
tiocytes, fibroblasts, undifferentiated mesenchymal cells and schwann with minimal residual disease at second look MRI.
cells have been implicated but the histogenesis still remains unknown.

Sunday, 8 September 2019 – Wednesday, 11 September 2019

E-PS-07-045 E-PS-08 | Endocrine Pathology
Correlation between radiologic diagnosis and pathological results in
resectable pancreatic neoplasms
G.M. Parini1, M.T. Rodrigo Calvo1, M. González Farrè1, C.V. Martinez E-PS-08-001
Stocker2, F.F. Díaz Rojas2, M. Pumar Perez2, G. Aguilar Sanchez2, X. Alveolar echinococcosis of the adrenal, accidental discovery
Duran3, A. Radosevic2, B. Lloveras Rubio1,4,3, M. Iglesias Coma1,4,3 Z. Merad1
1 1
Pathology Department. Hospital del Mar, Barcelona, Spain, CHU Sidi Bel Abbes, Algeria
2
Radiodiagnostic Department. Hospital del Mar, Barcelona, Spain,
3
Institut Hospital del Mar d'Investigacions Mèdiques, Spain, Background & Objectives: We repport a case of alveolar echinococco-
4
Universidad Autónoma de Barcelona, Spain sis confirmed histologically discovered in bilan of extension at a woman
presented a cancer of the endometrium and discuss the differential
Background & Objectives: Diagnostic imaging is important to evaluate diagnosis.
pancreatic neoplasms. Accurate detection and staging are essential for Methods: 75-year-old woman, followed in gynaecology for a cancer of the
ensuring appropriate treatment. The radiologic diagnosis includes the endometrium to whom the realized abdominal ultrasound found a mass in the
macroscopic appearance, neoplastic type, staging and atrophy, among right adrenal heterogeneous of 6 cms on 4 cms of size. The biological exam-
others. Pathological reports include also these variables. We want to es- inations were normal (17 ketostéroïd, 17 hydroxycortisone, metanephrine and
tablish the correlation between the pre-surgical radiologic diagnosis and acid vanillyl-mandelic). The abdominal CT objectified an adrenal mass het-
the final pathological report. erogeneous right of 6 cms on 4 cms. This mass adrenal is not functional who
Methods: We reviewed the radiological and pathological report of 120 sur- raised a problem of natural diagnosis.
gical pancreatic lesions (2014-2018, Hospital del Mar). The variables collect- Results: A coelioscopy explorer was practised with an extemporaneous
ed were: location, macroscopy, diagnosis, staging, lymph nodes and atrophy. examination which showed a fibrous fabric reshaped by the necrosis and
We use the Cohen's kappa coefficient statistical test to find the correlation. the beaches microphone - abscess which did not end in a diagnosis of
Results: The correlation between radiological and pathological diagnose certainty. A right adrenalectomy was practised. The histologically adrenal
is 71,43% (k of 0,58). The differences in diagnosis are mostly related to gland was completely erased by alveolar architecture, of many cavities of
neoadjuvant treatment, malignant cystic lesions without cystic compo- variable sizes which contained fragments of cuticle with presence in their
nent in surgical specimens and NET-like in radiology consistent with lights of proto scolex.
clear cell renal carcinoma metastasis. There is 97,17% in agreement in The evolution after operating were simple and patient went out one week
location and 60,5% in macroscopy. The correlation drops in relation with later.
affected lymph nodes (58,47%) and with atrophy (50%). Conclusion: Alveolar hydatid disease of the adrenal is an exceptional
Conclusion: We found an optimal correlation between radiological and path- pathology it will raise with any cystic tumour of the adrenal, especially
ological diagnoses, which is important in order to establish a possible surgical in endemic countries. However, the definitive diagnosis remains the pre-
treatment and behaviour, and also with location. In addition, we are able to rogative of the pathological examination, especially as prevention is dif-
explain the cause of the discrepancy in the majority of un-correlated cases. ficult given the parasitosis cycle takes place in nature.

E-PS-07-049 E-PS-08-003
Solid-pseudopapillary neoplasm of the pancreas: an institution's ex- Case report: co-existance of papillary thyroid carcinoma and follic-
perience and literature review ular carcinoma as a rare collision tumour
G. Gerardo1, R. Veiga1, A. Catarino1 M. Shariati1
1 1
Hospital da Luz Lisboa, Portugal Surgical Pathology Laboratory, Iran
 Virchows Arch

Background & Objectives: The simultaneous occurrence of different E-PS-08-006

types o f thyroid carcino ma in a s in g le pa ti en t i s a rar e Familial paraganglioma and morphologic criteria importance
event.Synchronization of PCT and follicular thyroid carcinoma (FCT) is T.M. Costa1, C. Albuquerque1, R. Sampaio1
1
very rare.So far a few cases (less than 5 cases) of the simultaneous oc- Centro Hospitalar Lisboa Ocidental, Portugal
currence of the papillary thyroid carcinoma and follicular thyroid carci-
noma have been reported.This article introduces a rare thyroid malignant Background & Objectives: Paraganglioma is a rare neuroendocrine tu-
case in the world that shows bilateral collision tumour of Papillary thyroid mour that arise from neural crest cells. Despite of great importance, there
carcinoma and Follicular thyroid carcinoma in a 66 year-old iranian is still no consensual morphologic prognostic criteria for these tumours.
female. Methods: A 46-year-old woman presented to our emergency department
Methods: In macroscopic examination, total thyroid weight was 30 g and due to tension headache followed by nausea, sweating and syncope as-
measured(right: 4.5 * 3.0 * 2.0 centimetres and 1.2 cm 3.0 * 2.2 * 1.5 sociated with extreme arterial hypertension. After exclusion of neurolog-
centimetres).Also, the gross evaluation of specimen showed encapsulated ical and cardiogenic causes it was found an intra-abdominal mass;
thyroid without macroscopic capsular invasion.Serial cutaways revealed Adherent to left renal vein, limited superiorly by the spleen, laterally by
several nodules with different size and calcification which were filled the the left kidney and adrenal gland, and posteriorly adherent to the thoracic
whole right thyroid lobe.The largest one was 3.5 cm in dimension.One vertebra. The laboratory workup showed elevation of methanephrines,
the other side,there were two nodule without calcification in the left lobe( and with high suspicion of a paraganglioma she underwent surgical
the great dimension was 3.0 cm). removal.
Results: Microscopic histopathological examination of right nodule con- Results: On gross examination was a nodule with 39g and 6,5x4,5x3cm,
firmed papillary thyroid carcinoma with complex branching papillae, in section yellow with central cystic area of hematic content.
fibrovascular cores and characteristic nuclear features: nuclei show over- Histologically was a paraganglioma, with large and irregular cell nests,
lapping, optically clear chromatin, nuclear longitudinal grooves and eo- moderate cellularity, pseudorosettes, vascular invasion, Ki67 3-5% and
sinophilic intra-nuclear inclusions.And left nodule slides revealed encap- capsular infiltration. According to Grading System of the Adrenal
sulated follicular carcinoma with capsular invasion. Solid pattern of small Phaeochromocytoma and Paraganglioma (GAPP) the tumour was classi-
and normal size follicles without nuclear features of papillary thyroid fied as moderately differentiated.
carcinoma.ΩCapsular invasion were noted in two sites. One site: full Conclusion: The immediate follow-up was benign; however, 3 months
thickness penetration through the capsule and the other: mushroom-like later, the patient is having symptomatology recurrence. Genetic testing
invasion through the capsule. disclosed a familial paraganglioma, with a germline mutation in succinate
Conclusion: Our presentation expresses the presence of two distinct dehydrogenase-subunit B gene, which has worse prognosis. The patho-
types of thyroid carcinoma (papillary and follicular carcinoma) in two logical report in this case was crucial to identify an uncommon
different lobes, which in turn is very rare in the world. paraganglioma and alert the clinicians for patient vigilance, genetic test-
We discussed some hypothesis for explaining the simultaneous occur- ing and evaluation of relatives.
rence of thyroid carcinomas in this case report article.

E-PS-08-007
E-PS-08-005 Morphological features of the parathyroid glands in rats under
Concomitant pheochromocytoma and adrenal adenoma in the same heavy metal salts influence
adrenal gland O. Tymakova1, N. Hryntsova 1 , O. Romaniuk1 , Y. Kuzenko2 , A.
T.M. Costa1, C. Albuquerque1, R. Sampaio1 Korobchanska3, I. Kravtsova1, A. Romaniuk1
1 1
Centro Hospitalar Lisboa Ocidental, Portugal Sumy State University, Ukraine, 2 Sumy State University, Department
of Pathology, Ukraine, 3 Kharkiv National Medical University, Kharkiv,
Background & Objectives: Both adrenal adenoma and pheochromocy- Ukraine
toma in the same adrenal gland concomitantly is a rare pathology, to our
knowledge with only 6 reported cases until now. Background & Objectives: The aim of this study was to explore the
Methods: A 61-year-old female, presented with primary morphological features of the parathyroid glands in the experimental
hyperaldosteronism and a left adrenal gland mass on the CT scan which animals under the heavy metal salts influence.
was consistent with adrenocortical adenoma. Her past medical history Methods: The experiment was conducted on 18 mature male albino rats,
was resistant arterial hypertension, type 2 Diabetes Mellitus and hyper- which were divided into 3 groups. The first group (C) was the intact ani-
cholesterolemia. The biochemical tests showed hyperaldosteronism, mals. During 30 days the rats of the second group (HMS 30), as well as the
strongly suggesting the diagnosis of adrenal gland adenoma, and so she animals of the third group (HMS 90) during 90 days got the water solution
underwent surgical removal. The pathological gross examination of the of heavy metal salts mixture (Zn,Cu,Fe,Mn,Pb,Cr). The functional activity
suprarenalectomy specimen revealed two separate tumours: one yellow of the parenchymatous glands structures was immunohistochemically
cortical nodule 1x0.9x0.7cm and a greyish medullary one with assessed, the expression of the chromogranin in cells was determined.
0.6x0.6x0.5cm. Results: On the 90th day the capsule thickness was nearly twice thicker,
Results: On microscopic examination we identified an adrenocorti- the connective-tissue layers in the parenchyma were increased in 3.8
cal adenoma and a pheochomocytoma. There has been reported times. The hypertrophy, as well as cytoplasm vacuolization were ob-
cases associating essential hypertension and pheochromocytomas served in the parathyrocytes. The parathyrocytes area in experimental
to cause adrenal hyperplasia and consequent adrenal adenoma for- animals was twice increased, on the 90th day – in 1.9 times. The cell
mation. In fact the incidence of adrenal adenomas in patients with nucleus area increased in 2.3 times on the 90th day. The immunohisto-
essential hypertension is increased. So there is a chance that our chemical study revealed the suppression of the chromogranine expression
adrenal adenoma could be resultant of an undetected in the parathyrocytes.
pheochromocytoma. Conclusion: The toxic action of heavy metal salts was the most signifi-
Conclusion: We think that this case is noteworthy in highlighting the cantly expressed on the 90th day by the proliferation of the connective-
importance of biochemical tests studying an adrenal mass to rule out tissue capsule. The increased area of parathyrocytes and cell nucleus area
pheochromocytoma prior to surgery, especially due to possible dangerous was observed. The most significant increase in the cell nucleus was ob-
intra-operative hemodynamic consequences, as well to understand the served on 90th day. The chromogranine expression decreased under the
hypertension ethiology. heavy metal salts influence.
Virchows Arch

E-PS-08-008 Conclusion: Expression of CK7 in diagnostic biopsies of NET metasta-

Clinical presentation of medullary thyroid carcinoma as "triple neg- ses of unknown origin allows to exclude the localization of primary
ative" breast cancer: case report and literature review tumours in the pancreas, intestines, skin, nasopharynx, kidney; suggests
M. Mchedlishvili1, N. Kekelidze2, K. Khachapuridze2, E. Imerlishvili2 their origin from the thyroid gland, breast, trachea and for CK7-positive
1
A. Natishvili Institute of Morphology, TSU, Georgia, 2 TSU, Georgia SCNEC and LCNEC the probability of their localization in the lung and
stomach is very high.
Background & Objectives: Medullary Thyroid Carcinoma is a ma-
lignant tumour of C-cells, which can be manifested in different
organs as a metastatic disease. The most common metastatic sites E-PS-08-011
are - bones (45%), lungs (33%), brain (1-5%) skin and rarely in Thyroid angiosarcoma in a non-alpine country. A case report and
breast. According to the literature only 25 cases of medullary thy- review of the literature
roid cancer metastasis in breast are described. None of them was P. Ravazoula1, D. Koumoundourou1, E. Mpota1
1
primarily manifested in breast involving axillary lymph nodes as University Hospital of Patras, Greece
well.
Methods: The article describes clinical cases of two patients with Background & Objectives: Thyroid angiosarcoma is a malignant neo-
medullary thyroid carcinoma.The first case describes 71 years old plasm which is reported in Alpine region countries of central Europe. It is
man with medullary thyroid carcinoma in breast, lesion localization manifested as a ‘cold nodule” most often in eldery female patients. We
- in the upper-lateral quadrant of the breast, tumour size was 3.2 x present a case of thyroid angiosarcoma in a non-alpine country.
2.0 x 1.8 cm (the first patient). The second patient was 13 year-old Methods: A 69 years old woman presented with a right lobe thyroid
boy with thyroid medullar-microcarcinoma. The both patients were nodule measuring 2,2cm. in greatest diameter. Ten years ago she
examined by immunohistocemistry. Examination was done with sur- had underwent a total mastectomy and had recieved radiotherapy.
gical samples of tissue. Fine needle aspiration cytology revealed “epithelioed malignant
Results: The first patient - negative expression of ER,PR,HER-2. cells”. Histological examination showed a malignant neoplasm with
Expression of proliferation marker Ki67 was very low. S100 (+) – areas of necrosis and anastomosing channels lined by medium size
expressed in tumour cells; Calretinin - strongly positive; Post surgical cells with abundant eosinophilic cytoplasm, large nucleus with
thyroid ultrasound examination revealed 1.7 cm tumour in the left lobe. prominent nucleoli and numerous typical and atypical mitoses.
Calcitonin level in blood was 1037. 4pg/ml. The multiple metastasis There was invasion of sternoyoid muscle.
caused patient death within three years. The second patient - following Results: Immunocistochemically tumos cells were positive for
our recommendation patient’s grand-child examined and 0.4 cm thyroid CD31, CD34 and Vimentin, focally positive for low molecular
medullary carcinoma of the left lobe was diagnosed. weight keratins and S-100 protein and negative for thyroglobulin,
Conclusion: There are extremely rare cases of Medullary Thyroid calcitonin, galectin, TTF-1, Melan A, HMB45, ER, PR, CEA. The
Carcinoma with clinical manifestation in breast as a “classical” breast diagnosis was that of an angiosarcoma.
cancer. “Triple negative”malignant lesions of breast need carefully exam- Conclusion: We described a case of thyroid angiosarcoma in a
ination to exclude tumour metastasis in breast. In order to verify malig- patient living in a non-alpine region with a history of radiation
nancy at an earlier stage, screening of patient’s family members is very therapy. Thyroid angiosarcomas are rare malignant tumours main-
important. ly with poor prognosis and most patients die in less than six
months. Differential diagnosis includes anaplastic thyroid carcino-
ma with angiomatoid feature.
E-PS-08-009
Value of Cytokeratin 7 expression to determine the origin of metas-
tases of neuroendocrine tumours E-PS-08-012
L. Gurevich1, V. Ashevskaya1, E. Bondarenko1, I. Voronkova1, M. Primary paraganglioma of thyroid gland: a rare case report with
Byakhova1 clinicopathologic and immunohistochemical analysis
1
The State Budgetary Healthcare Institution of Moscow Area Moscows R.A. Barna1, M. Cornianu2, A. Faur3, G. Oprisan1, A. Dobrescu4, F.
Regional Research Clinical Institute n.a. M.F. Vladimirskiy, Moscow, Lazar4,5
1
Russia Department of Pathology, University of Medicine and Pharmacy
„Victor Babes", Timisoara, Romania, 2 V. Babes University of
Background & Objectives: Recently, the problem of determining the Medicine and Pharmacy, Romania, 3 Anatomy and Embryology
localization of a primary neuroendocrine tumour (NET) on the material of Department, University of Medicine and Pharmacy „Victor Babes",
diagnostic biopsies of metastases of NET of unknown origin has become Timisoar, Romania, 4 Surgery Department II, University of Medicine
increasingly urgent. and Pharmacy „Victor Babes", Timisoara, Romania, 5 Surgery
Methods: The expression of cytokeratin 7 (CK7) was analysed 271 NETs Department II, Emergency County Hospital Timișoara, Romania
of various localization: 14 NET pancreas, 36 stomach (22 G1, G2; 8 G3:
4 small cells neuroendocrine carcinomas(SCNEC), 4 large Background & Objectives: Primary thyroid paraganglioma (PTPG) is a
cells(LCNEC)), 6 NET duodenum, 214 - lungs (100 typical (TC) and rare and unusual neuroendocrine tumour, most of the times it can be
atypical carcinoids(ATC); 85 SCNEC, 19 LCNEC), 6 - mediastinum, mistaken for other thyroid neoplasms.
14 - medullary thyroid cancers(MTC), 8 - breast, 4 – kidneys, 2 - tracheas, This study reports a case of PTPG accompanied with euthyroidism,
2 - nasopharynx. which mimics medullary thyroid carcinoma, from a 44-year-old woman
Results: The expression of CK7 was detected in 100% of MTC, who presented with dyspnea and dysphonia caused by an anterior cervical
breast, trachea, and was completely absent in all NETs of the pan- lesion.
creas, duodenum, Merkel carcinomas, nasopharyngeal carcinoids Methods: Physical examination revealed a painless, well-circumscribed
and kidney. Expression of CK7 was detected in 22.7 (5/22) gastric thyroid nodule of 3 cm within the left lobe, with normal mobility and
carcinoids G1, G2, and in 75% (6/8) and NEC G3, in 17% (9/53) without palpable cervical lymphadenopathy.
TC and 54.4% (27/47) ATC of lung, in 51.6% (49/95) of SCNEC Ultrasonography (US) of the thyroid gland showed a nodule in the left
and 68.4% (13/19) of LCNEC of lung, 16.7% (1/6) of mediastinal lobe measuring 30 mm, hypoechoic, with increased intranodular vascular
carcinoids. flow. The laboratory examination results were in normal range. US and
 Virchows Arch

computed tomography had no diagnostic value. Later, the patient who underwent total thyroidectomy, thyroid gland was lobule, solid appear-
underwent surgical resection of the left thyroid lobe. ance. Microscopic examination of the thyroid revealed diffuse infiltration of
Results: PTPG diagnosis was determined by histopathological features and the parenchyma by mature fat tissue and atrophic thyroid follicles. An
confirmed by immunohistochemical staining. The specimen showed posi- eosinophilic amorphous material consistent with amyloid substance infil-
tivity for chromogranin A (CgA), synaptophysin (Syn), neuron-specific trated these fat tissue. This material stained intensely with Congo red and
enolase (NSE) and CD56, whereas it was negative for TTF-1, calcitonin was apple green in color under polarized light. Most of the areas of the
and carcinoembryonic antigen (CEAm); S-100 protein was positive in thyroid gland consisted of solid cell nests between these fat tissue.
sustentacular cells located at the periphery of the tumour cell nests. Results: Amyloidosis is results from the deposition of insoluble, fibrous
After performing surgical resection as a curative approach, at 36 months amyloid proteins, nearly always in the extracellular spaces of organs and
of follow up there is no local recurrence or metastasis. tissues. Amyloid deposition in the thyroid parenchyma is rare and usually
Conclusion: Becoming aware of the existence of PTPG and recognizing accompanies medullary carcinomas.
its histological characteristics is essential for the diagnosis and treatment Conclusion: The origin of adipose tissue accompanying amyloid goiter is
of the lesion. Even though it is hard to diagnose, PTPG seems to have a unknown.Diffuse accumulation of metaplastic fat tissue should be differ-
favourable prognosis and preferred treatment option is total thyroidecto- entiated from diffuse thyrolipomatosis of thyroid gland. Amyloid stains
my with long-term follow-up. can be helped us for the differential diagnosis.

E-PS-08-013 E-PS-08-016
Neuroendocrine tumours: an observational study Neuroendocrine cells relevant to endocrine mammary and cutaneous
V. Tudorache1 carcinomas: nature and significance
1
Universitatea de Medicina si Farmacie Targu Mures, Romania T. Kawasaki1,2, T. Kubota2, R. Katoh3,4, T. Kondo3, S. Ichihara2, K.
Horibe2, H. Nagai2, M. Takahashi5
1
Background & Objectives: Neuroendocrine tumours (NETs) predomi- Saitama Medical University International Medical Center, Japan,
2
nantly affects the gastrointestinal tract but other organs can also be in- National Hospital Organization Nagoya Medical Center, Japan,
3
volved. The aim of the paper was to perform a retrospective evaluation of University of Yamanashi, Japan, 4 Ito Hospital, Japan, 5 Nagoya
NETs diagnosed in our department in the last years. University, Japan
Methods: Consecutive cases of NETs diagnosed during 2009-2017 in
Department of Pathology of University of Medicine, Pharmacy, Background & Objectives: The developmental mechanisms of neuro-
Sciences and Pathology, were retrospectively evaluated. endocrine carcinomas (NECs) of the breast and the skin have not been
Results: There were 175 cases diagnosed in 9 years, with a median sufficiently analysed and are not well understood. The aim of this study
number of 19.44±5.27 cases per year (range 11-28) and a M:F ratio of was to investigate neuroendocrine (NE) cells in the background tissues
1.18:1. The median age of patients was 59.09±15.75 years (range 8-92 surrounding mammary and cutaneous NECs.
years). The predominant locations were appendix (34%), stomach (17%) Methods: Four Japanese cases (four breasts and one eyelid) having solid
and pancreas (16%), followed by tumours of colorectal segments (9%), papillary NECs accompanied by many NE cells were identified. These
small intestine (7%), lung (7%) and adrenal glands (3%). The other cases patients were, respectively, 28-, 31- and 38-year-old women (breasts) and
(7%) were diagnosed in genital organs, head and neck area, and gallblad- 51-year-old man (eyelid) with no familial history of NE tumour. The
der. Most of the tumours (n=132) were carcinomas (36 out of 132 cases totally resected breasts and excised skin of the eyelid were serially studied
showed lymph node metastases), the other 43 tumours being diagnosed as by immunohistochemistry for specific NE markers and the morphologies
G1- (n=33), G2- (n=5) or G3-NETs (n=5). and/or localization of NE cells were investigated.
Conclusion: Most of the NETs are localized in the gastro-entero- Results: Immunohistochemical examination showed extensively-
pancreatic area and show a malignant behavior. distributed NE cells in the background terminal duct-lobular units or
sweat ducts of NECs. These NE cells reactive for chromogranin A and/
This work was supported by a grant of the Romanian National Authority or synaptophysin were classifiable into three emerging patterns: isolated/
for Scientific Research, CNCS – UEFISCDI, project number 20 scattered, clustered and circumferential. NE cells were morphologically
PCCF/2018, code: PN-III-P4-ID-PCCF-2016-0006. polygonal, oval or columnar with sometimes eosinophilic and/or fine-
granular cytoplasm and round-to-ovoid nuclei lacking atypia. Some cells
were located between epithelial and myoepithelial cells. Apical snouts
E-PS-08-015 were occasionally observed in NE cells forming luminal structures.
Multiple solid cell nests accompanying amyloid goiter: a rare case Conclusion: Benign-looking NE cells in the parenchyma of a skin as well
report as a breast with NEC could be regarded as hyperplastic from their emerg-
Î Kaya1, S. Ekmekci2, Į Sert3, Î Küçük1 ing patterns and distribution; this “NE cell hyperplasia” may be associat-
1
Izmir Tepecik Education and Research Hospital, Department of Pathology, ed with the histogenesis of NEC as a precancerous condition. These
Turkey, 2 Izmir Tepecik Training and Research Hospital, Department of observations might raise questions about the treatment for NEC. (J Clin
Pathology, Turkey, 3 Izmir Tepecik Education and Research Hospital Pathol, 2012 & Pathology, 2018).
Department of General Surgery, Turkey Grants-in-Aid for Scientific Research (16K08654 & 16H00668) from the
Japanese Ministry of Education, Culture, Sports, Science and Technology
Background & Objectives: Amyloid goiter is a disease that results in and National Hospital Organization (NHO) Grant (H29-NHO-01).
diffuse growth of the gland due to the accumulation of amyloid protein in
the thyroid gland. In systemic amyloidosis, all the organs as well as
thyroid glands can be infiltrated with amyloid.This report presents a E-PS-08-017
new case of amyloid goiter with diffuse fat deposition which may be Bone metastases of unknown primary in a patient with bilateral
confused with other pathological conditions of the thyroid gland. ovarian tumour and thyrotoxicosis - an unusual case of highly differ-
Methods: A 32-year-old male patient, had undergone renal transplantation entiated follicular carcinoma of ovarian origin (HDFCO) [malignant
5 years ago due to chronic renal failure, was admitted to our endocrinology struma ovarii]
department with a rapidly increasing mass localized in front of his neck and O. Stanowska1, O. Kuczkiewicz-Siemion1, J. Gałczyński2, E. Bakuła-
hypothyroidism findings. In the macroscopic examination of the patient Zalewska3
Virchows Arch

1
Maria Sklodowska-Curie Institute - Oncology Center, Department of schwannian stroma and dispersed neuroblastic elements, mostly ganglion
Pathology and Laboratory Medicine, Poland, 2 Department of cells and neuroblasts of intermediate differentiation.
Oncological Endocrinology and Nuclear Medicine, Maria Sklodowska- Immunohistochemically, the schwannian stroma was highlighted with
Curie Institute - Oncology Center, Warsaw, Poland, 3 Department of S100 and neuropil with synaptophysin; the neuroblastic elements stained
Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie consistently with PHOX2B, mostly with VIP, and variably with S100,
Institute - Oncology Center, Warsaw, Poland synaptophysin, chromogranin and CD56; the phaeochromocytoma was
positive for synaptophysin, chromogranin, CD56 and PHOX2B.
Background & Objectives: Struma ovarii (SO) is a monodermal terato- Ki67/MIB-1 was detected in 1% of the nuclei of both components.
ma with preponderance of thyroid tissue. Conclusion: These features are diagnostic of composite
Rarely, it undergoes malignant transformation, most often to papillary or phaeochromocytoma with a differentiating neuroblastic component. The
follicular thyroid-type carcinoma. neurogenic component is usually a ganglioneuroma or a
SO may present as HDFCO, which histologically resembles normal thy- ganglioneuroblastoma; a neuroblastic component is very rare, mostly
roid tissue or follicular adenoma but displays malignant behavior. undifferentiated. The (ganglio)neuroblastic component is usually identi-
We present a case of HDFCO with bone metastasis. fied reliably on morphological grounds. Immunohistochemically,
Methods: 68-year old woman with thyrotoxicosis and hypertension pre- PHOX2B is considered the best marker for the peripheral autonomic
sented with pelvic mass palpated per rectum during evaluation for nervous system. VIP highlights neuronal elements and its expression
constipation. may be associated with functional manifestations. Surgery is curative in
Radiology tests demonstrated bilateral bulky ovarian tumours with mul- most cases, even with an extensive neuroblastic component.
tiple bone metastases. The patient underwent total hysterectomy and
adnexectomy with histopathological examination that was not conclusive
for metastases’ site of origin. E-PS-08-021
Subsequent spine biopsy was prompted which resulted in detection of Molecular profiling of follicular-patterned thyroid tumours in a
metastatic thyroid tissue. Romanian population highlights distinct clinical, pathological and
Total thyroidectomy was required. follow-up features between BRAFV600E versus RAS positive
Results: Histopathological assessment of bilateral oophorectomy speci- genotypes
mens revealed strumal carcinoid in mature teratoma of the left ovary (SC) A. Nechifor-Boila1, A. Cota1, C. Banescu2, V. Moldovan2, F. Descotes3,
and giant SO in the right ovary. M. Decaussin-Petrucci4, D. Piciu5, A. Borda1
1
Entirely submitted thyroid gland demonstrated only papillary Department of Histology, UMFST Targu-Mures, Romania,
2
microcarcinoma (PMC). Department of Genetics, Center for Advanced Medical and
Reevaluation of the bone biopsy excluded papillary carcinoma Pharmaceutical Research, UMFST Targu-Mures, Romania,
3
metastasis. Department of Biochemistry, Molecular Biology, Centre Hospitalier
Diagnosis of HDFCO was made based on microscopic appearance of Lyon Sud, Hospices Civils de Lyon, Pierre Benite, France,
4
bone metastasis [degenerative thyroid tissue, Thyroglobulin (+), TTF- Department of Pathology, Centre Hospitalier Lyon Sud, Hospices Civils
1(+)] coexisting with struma ovarii, without presence of eutopic follicular de Lyon, Universite Lyon 1, Pierre Benite, France,
5
carcinoma. Department of Nuclear Medicine "Ion Chiricuta" Institute of Oncology,
PMC of the thyroid gland and SC were recognized as incidental findings. Cluj-Napoca, Romania
The patient remains stable under adjuvant radioactive iodine therapy with
antithyroid treatment. Background & Objectives: The aim of our study was to assess in a
Conclusion: Our case supports the previous reports of malignant poten- Romanian population the prevalence of BRAFV600E and RAS mutations
tial of histologically benign SO and confirms that tumour with size >10 in follicular-patterned thyroid tumours, and to correlate the molecular
cm, thyroid tissue >80%, adhesions, peritoneal fluid and ovarian serosal results to the clinico-pathological and follow-up data.
rent should be evaluated as HDFCO. Methods: All cases of papillary (PTC) and follicular (FTC) thyroid carcino-
mas registered at the Targu-Mures Pathology Department between 2008-
2015, with available follow-up data were reviewed by two pathologists and
E-PS-08-020 re-classified into one of the following categories: conventional PTC (CPTC),
Composite phaeochromocytoma with a differentiating neuroblastic follicular variant PTC (FVPTC), other variants PTC, FTC and NIFTP (non-
component in a 71-year-old man invasive follicular thyroid neoplasm with papillary-like nuclear features). All
C. Masaoutis1, A. Sykaras2, F. Dolkiras1, K. Stefanaki3, I. Provatas1, T. cases were subjected to RT-PCR amplification targeting the BRAFV600E and
Choreftaki4, A. Angelousi5, G. Kyriakopoulos6 RAS (KRAS, NRAS, HRAS) somatic mutations.
1
Evaggelismos General Hospital of Athens, Greece, 2 Department of Results: Our study included 165 cases: 80(48.5%) CPTCs, 14(8.5%)
Pathology, Evangelismos General Hospital, Athens, Greece, FVPTCs, 20(12.1%) PTC other variants, 5(3%) FTCs and 46(27.9%)
3
Aghia Sofia Children's Hospital, Greece, 4 Department of Pathology, NIFTPs. Among these cases, 55(33.3%) were BRAF V600E and
General Hospital of Athens "G. Gennimatas", Athens, Greece, 5 1st 31(18.8%) RAS positive. The majority of BRAFV600E positive cases
Department of Internal Medicine, Laiko University Hospital, National (92.7%) were CPTCs. Any NIFTP case was associated with
and Kapodistrian University of Athens Medical School, Athens, BRAFV600E mutation. Compared to RAS, BRAFV600E positive tumours
Greece, 6 Department of Biological Chemistry, Medical School, revealed a higher rate of multifocality (p=0.023), extrathyroidal extension
National and Kapodistrian University of Athens, Athens, Greece (p=0.002) and lymph node involvement (p=0.001). All patients with RAS
positive tumours were disease free at the last clinical assessment, com-
Background & Objectives: A 71-year-old man was subjected to right pared to BRAFV600E positive patients (only 85.5%, p=0.026).
adrenalectomy due to an asymptomatic adrenal tumour measuring 3,7 cm Conclusion: In our study BRAFV600E and RAS positive tumours revealed
in greatest diameter. distinct clinical, histo-pathological and follow-up features. Assessment of
Methods: Light microscopy and immunohistochemistry. tumours’ molecular profile could play a role in a better risk-stratification
Results: Microscopy revealed a biphasic tumour, resembling a typical of the patients in need for additional post-surgery treatment.
phaeochromocytoma to the greater extent (~80%) and a neurogenic tu-
mour to a lesser extent (~20%). The neurogenic component consisted of This work was supported by the University of Medicine and Pharmacy of
centrally located nodules of ample neuropil with rare (<10%) foci of Targu-Mures Research Grant No. 275/1/11.01.2017.
 Virchows Arch

1
E-PS-08-022 Pathology Department - Hospital Pedro Hispano, Portugal, 2 Unidade
Angioinvasive, poorly differentiated thyroid carcinoma developed on Local de Saúde de Matosinhos - Portugal
an oncocytic follicular carcinoma: report of a challenging case
A. Nechifor-Boila1, S. Cristina2, R. Catana1, C. Carasca3 and A. Borda1 Background & Objectives: Hobnail variant of papillary thyroid carci-
1
Department of Histology, UMFST Targu-Mures, Romania, 2 Department of noma (HVPTC) is a rare and aggressive tumour defined as a papillary
Pathology, Targu-Mures Emergency County Hospital, Romania, carcinoma (PTC) with > 30% of tumour cells with hobnail features. We
3
Department of Forensic Medicine, UMFST Targu-Mures, Romania report a case of HVPTC.
Methods: Clinical history, macroscopic and histological features have
Background & Objectives: Poorly differentiated thyroid carcinoma been reviewed.
(PDTC) is a rare, but clinically significant entity because it accounts for Results: A 72-year-old woman with 40 mm nodule in the right thyroid
most fatalities from non-anaplastic follicular cell-derived thyroid cancer. lobe was submitted to fine needle aspiration: the result was papillary
Methods: We report the case of a 68-years-old male admitted to the carcinoma. She underwent thyroidectomy: in the right lobe was a
hospital for a large, compressive thyroid goiter. Total thyroidectomy 45 mm encapsulated nodule with cystic and solid areas, yellowish and
was performed and the specimen was sent to the Pathology Department. friable. Histologically, the lesion had a complex papillary and
Results: On gross examination, the left thyroid lobe was almost entirely micropapillary architecture with prominent vascular cores (sometimes
replaced by a gray- whitish nodule of 105-mm with extensive necrosis. On with foamy histiocytes) and areas with cellular discohesiveness. These
microscopy, the nodule was surrounded by a thick capsule, with capsular and papillary structures were lines by cuboidal/columnar cells with eosino-
extensive vascular invasion. The architectural pattern was solid or trabecular, philic cytoplasm and high N/C ratio. Nuclei were apically placed, some-
with large tumour sheets or tumour cords/ribbons, separated by thin, fibro- times with grooves and pseudoinclusions, producing a surface bulge.
vascular septa. Extensive foci of endocrine-type necrosis were present in the These hobnail/micropapillary features were present in approximately
centre of the tumour sheets. The tumour was composed entirely of oncocytic 75% of the lesion. Microcalcification was observed. Vascular invasion
cells, with abundat eosinophilic cytoplasm and small, slightly irregular, cen- was identified; there was no capsule invasion. Necrosis was absent and
trally placed nuclei, with prominent nucleoli. The mitotic index was 6 mitosis/ mitosis was scant. Immunohistochemically: TTF-1 and p53 (focal) pos-
10HPF. A minor component of well-differentiated oncocytic follicular carci- itive. Patient was diagnosed with HVPTC pT3a Nx R0; no distant me-
noma was also observed. Immunoreactivity for Thyroglobulin was restricted tastasis was identified. BRAF, NRAS and TERTp mutations were nega-
to isolated tumour cells (mainly in a perinuclear dot-like pattern) or in few tive. Patient was treated with radioiodine; she is well and under clinical
residual microfollicles. Immunostainning for CEA, Chromogranin and surveillance (10 months follow-up).
Synaptophisin were negative. A final diagnosis of angioinvasive PDTC de- Conclusion: HVPTC is a particularly aggressive and invasive tumour.
veloped on an oncocytic follicular carcinoma was set. Patients with this diagnosis should be observed closely for recurrent dis-
Conclusion: The diagnosis of PDTC can be challenging, especially in ease.
oncocytic tumours. The presence of a co-existent well-differentiated com-
ponent is an important morphological aid that helps and must be searched
for the correct assessment of the final diagnosis. E-PS-08-025
Hobnail variant of papillary thyroid carcinoma associated with a tall
cell component: report of an unusual, rare case
E-PS-08-023 A. Borda1, B. Nagy2, E. Szasz1, R. Catana1, A. Cota1, A. Nechifor-Boila1
1
Karyometric analysis of thyroid gland tumours Department of Histology, UMFST Targu-Mures, Romania, 2
D. Mihailovic1, Ů Mijović1 Department of Pathology, Targu-Mures Emergency County Hospital,
1
Institute of Pathology, Medical Faculty, University of Nis, Serbia Romania

Background & Objectives: Papillary carcinoma is the most commonly Background & Objectives: The hobnailvariant of papillary thyroid car-
diagnosed malignant tumour of the thyroid gland and makes 85% of all cinoma (HVPTC) is recognised as a new variant of PTC in the fourth
tumours of the thyroid gland. The aim of this study was karyometric analysis edition of the WHO 2017 Classification Tumours of Endocrine Organs.
of papillary carcinomas and follicular adenomas of the thyroid gland. Methods: We report the case of a 65-years-old female admitted to the
Methods: This study includes 23 tumours, 13 follicular adenomas, and hospital for suspicion of a thyroid malignant neoplasm. Total thyroidec-
10 papillary carcinomas. The material was obtained by thyroidectomy in tomy with lymph node dissection was performed and the specimen was
the Clinical Center of Niš from 2000-2017. All thyroid tumours were sent to the Pathology Department.
analysed immunohistochemically using monoclonal MIB-1 antibodies Results: On gross examination, both the right and left lobe of the
for Ki-67 antigen, and “ImageJ" software was used for karyometric anal- thyroid were entirely replaced by a gray-whitish tumour mass. On
ysis. After manual editing of binary images, seven nuclear parameters microscopy, the tumour exhibited complex papillary structures,
were estimated: nuclear area, optical density, perimeter, circularity, lined by cells with abundant, eosinophilic cytoplasm, apically locat-
Feret’s diameter, integrated optical density (IOD) and Ki-67 index. For ed nuclei with proeminant nucleoli and loss of cellular cohesion.
statistical analysis of the data MANOVA and t-test were used. The prob- This distinctive hobnail feature was associated with a “tall-cell”
ability of less than 0.05 was considered statistically significant (p<0.05). component: elongated, ribbon-like structures, lined by cells with
Results: Nuclear size (area, perimeter, and Feret’s diameter) and IOD abundant, eosinophilic cytoplasm, three times as tall as wide and
were significantly lower in papillary carcinoma than in follicular adeno- having typical nuclear features of PTC. The tumour cells stained
ma (p<0.05). Ki-67 index was higher in papillary carcinoma, but this positive for Thyroglobulin and TTF1, which confirmed the primary
difference was not statistically significant. Similarly, other differences origin of the tumour in the thyroid. A diagnosis of HVPTC associ-
were not statistically significant (p>0.05). ated with a tall-cell component was set. Extensive extrathyroid ex-
Conclusion: Our results indicate that nuclear size and IOD can be useful tension into strap muscles was documented. Multiple lymph node
parameters in diagnostic pathology of thyroid tumours. metastases, some with extra capsular extension revealing both hob-
nail and tall-cell-like PTC features were described.
Conclusion: Although rare, HVPTC is histologically unique and impor-
E-PS-08-024 tant to be recognised due to its very aggressive behaviour. It can be found
Hobnail variant of papillary thyroid carcinoma isolated, but more frequently associated with other aggressive histologic
J. dos Santos1, R. Machado-Neves1, T. Amaro1, M. Honavar2 types of thyroid cancers, like tall-cell variant as in this case.
Virchows Arch

E-PS-08-026 E-PS-08-028
Testicule feminisation: a case report Searching for Hodgkin - discovering a carcinoma ex pleomorphic
B. Laabidi1,2, R. Hedhli3, R. Yaich1,2, N. Mansouri1,2, F. Gargouri4, A. adenoma
Saidi1,2, A. Bouziani4, I. Msakni4 C. Dahlstedt-Ferreira1, J. Nogueira1, A. Galzerano1, J. Oliveira1
1 1
Tunis El Manar University, Medicine School of Tunis, Tunisia, Hospital Garcia de Orta, EPE, Portugal
2
Military Hospital of Tunis, Department of Pathology, Tunisia, 3 Tunis El
Manar University, Medicine School of Tunis Military Hospital of Tunis, Background & Objectives: Carcinoma ex pleomorphic adenoma (Ca ex
Department of Pathology, Tunisia, 4 Pathology Department; Military PA) is an entity arising from a benign pleomorphic adenoma, either pri-
Hospital for Instruction of Tunis, Tunisia mary or recurrent. It is a rare tumour, comprising 3,6% of all salivary
gland neoplasms, more predominant in women in the sixth to eighth
Background & Objectives: Testicule feminisation is an X-linked disease decades of life, affecting more often the major salivary glands.
characterised by variable defects in virilization of 46,XY individuals due Methods: A 42 year-old male, with known classical Hodgkin lymphoma
to resistance to the actions of the androgen hormones, which in turn stops (HL) diagnosis, presented with a mobile and painless mass on his right
the forming of the male genitalia and gives a female phenotype. It occurs parotid gland, which had been growing for 5 years, previously to the HL
in one out of 20,000 births. We report the clinical and pathlogic findings diagnosis. The subject underwent computerized tomograph, which de-
in a rare case of testicular feminization. scribed an intraparotideal adenomegaly, with necrosis. He was submitted
Methods: A 32-year-old woman presented with primary amenorrhea and to aspiration cytology and total parotidectomy.
infertility. Results: Grossly, the mass measured 4x2x3cm and appeared solid, with
Results: The clinical examination showed a female phenotype with nor- white and yellow colour, with expansive growth. Microscopically, it pre-
mally developed breasts, normal vulva and a short vagina. sented as a biphasic tumour, having myoepithelial cells and epithelial
Ultrasonography of pelvis showed absent uterus and hypo-echoic struc- cells with squamous differentiation and keratinization, within a condroid
ture with internal vascularity in bilateral inguinal region. Testosterone stroma. It had intraglandular extension and was minimally invasive, al-
was 6ng/ml. Laparoscopy showed absent uterus and presence of two though the surgical margins were not involved by the lesion.
pelvic masses reminiscent of ovarian structures. Bilateral gonadectomy Conclusion: Pleomorphic adenoma in the parotid gland is a benign and
was performed. Histologic examination of the nodules revealed two tes- common entity. However, in rare cases, it can undergo malignant trans-
tes, with atrophy of the seminiferous tubules, insufficient development of formation, having an aggressive behavior, with potential to metastize in
the germinal cells with hyperplasia of the Leydig cells. No signs of tes- 70% of cases. However, if it is intracapsular or minimally invasive, it has
ticular cancer and neither ovarian tissue were identified. Karyotyping was a more favourable outcome, hence the importance of surgical resection of
46 XY. Estrogen replacement therapy was introduced. a pleomorphic adenoma before it undergoes malignant transformation.
Conclusion: Testicular feminization is a rare disease that must be diag-
nosed and treated through collaborative interaction between gynecolo-
gists, geneticians and pathologists. Role of pathologists is to confirm E-PS-08-029
the presence of atrophic tests and absence of malignancy. Mixed medullary and follicular thyroid carcinoma: a rare and chal-
lenging case
I. Fridrihsone1,2, I. Briede1,2, A. Abolins1,2, I. Strumfa1,2, G. Bahs1,3
1
E-PS-08-027 Riga Stradins University, Latvia, 2 Department of Pathology, Latvia,
3
Elastic fibers in papillary thyroid carcinoma microenvironment Department of Internal Diseases, Latvia
S. Rjabceva1, M. Derevyanko1, I. Siamionik1, M. Vorobel1
1
Institute of Physiology of National Academy of Sciences of Belarus, Background & Objectives: Mixed medullary and follicular carcinoma is
Belarus a rare thyroid malignancy. To set the diagnosis, tumour must show both
follicular/thyroid and medullary/C-cell differentiation by morphological
Background & Objectives: The tumour microenvironment, com- features and immunophenotype. In addition, mixed pattern should be
posed of non-cancer cells and their stroma, was recognized as a retained in metastases.
one of major factor of cancer growth. The aim of this study is to Methods: Medical documentation, pathology slides and radiologic inves-
estimate the changes of stromal elastic fibers in papillary thyroid tigations were reviewed in the context of up-to-dated scientific literature.
carcinoma (PTC). Results: A case of mixed medullary and follicular thyroid carcinoma in a 42-
Methods: Review of hematoxylin-eosin slides of 44 cases PTC followed year-old-female is reported. TI-RADS 5 lesion by ultrasonography was
by stratification into groups based on tumour size. Histochemical studies suspected. Total thyroidectomy with right-sided lateral lymphadenectomy
for Russell-Movat pentachrome stain was done. was performed. At grossing, white, firm, ill-defined lesion involved right lobe
Results: According to tumour size all patients distributed as follows two and isthmus. By histology, polygonal cells with round nuclei, coarse chroma-
groups: with tumour size < 1.0 cm (1st group, 16/40.1%) and with tumour tin and amphophilic cytoplasm as well as amyloid deposits in stroma were
size > 1.0 cm (2nd group, 18/52.9%). Thickened elastic fibers in capsule observed. Cells were growing in nests; pseudopapillary architecture was ev-
of thyroid glands was found in 13/85.3% patients of the first group and in ident focally. Both entrapped and neoplastic follicles were present, showing
11/61.1% – of the 2nd group (Manna-Whitney test, p>0.05). Thickened markedly different nuclear features. Immunohistochemically, neoplastic cells
elastic fibers around vessels was found in 6/37.5% cases of the first group were reactive to calcitonin, CEA and synaptophysin. Expression of TTF-1
and in 3/16.7% – of the 2nd (Manna-Whitney test, p>0.05). Thickened was heterogeneous by intensity, correlating with follicular morphology.
elastic fibers in tumour microenvironment were detected in 7/47.8% pa- Metastases in lymph nodes (12/33) showed mixed medullary and follicular
tients of the first group and in 2/11.1 % – of the 2nd group (Manna- morphology with marked TTF-1 expression in follicular component and pos-
Whitney test, p=0,036). Gamma`s correlation analysis revealed the asso- itive calcitonin, CEA and low level of TTF-1 in medullary component, hence
ciations between an increasing of thickness of elastic fibers and tumour leading to diagnosis of mixed medullary and follicular thyroid carcinoma.
size (r=-0.37, p <0.05). Conclusion: Mixed medullary and follicular thyroid carcinoma is a rare
Conclusion: This study showed that the change in the thickness of thyroid tumour; thus it can be challenging, especially for young patholo-
the elastic fibers in PTC microenvironment is related to tumour gist. To reach the diagnosis, awareness of the entity is important.
size. Papillary thyroid microcarcinoma characterised by formed of Morphology, tumour heterogeneity and immunohistochemical findings
thickened elastic fibers in tumour stroma often than PTC with must be considered by integrated approach, looking for correlations be-
more tumour size. tween morphology and immunophenotype.
 Virchows Arch

E-PS-08-030 taxonomy to understand how neoplasms from different organ systems

Prevalence of atypical adenomas in an Algerian series of pituitary inter-relate clinically and genetically.
tumours
F. Terkmani1, S. Bakhti2, Z.C. Amir3, S. Mimouni4
1
Hospitalo University Center Mustapha, Algeria, 2 EPH Ait Idir, Algeria, E-PS-08-032
3
CHU Mustapha, Algeria, 4 CPMC, Algeria Adrenocortical adenomas with concurrent adrenal myelolipomas: a
single unit experience
Background & Objectives: Pituitary adenomas (PA) are defined as a D. Di Nanni1, A. De Leo2, F. Ambrosi3, G. Di Dalmazi4, G. Zavatta4, V.
group of slow-growing tumours. They are most often benign controlled Vicennati4, S. Selva4, C. Ceccarelli5, D. Santini1
1
by surgical resection and / or specific medical treatment, nevertheless the Pathology Unit, S. Orsola-Malpighi Hospital, University of Bologna,
aggressive pituitary adenoma which is characterised by an extension to Bologna, Italy, 2 1)Pathology Unit, Department of Experimental,
adjacent structures and pituitary adenomas recurrent or resistant to med- Diagnostic and Specialty Medicine, University of Bologna, S. Orsola-
ical treatment is a problem major care in current practice. Malpighi Hospital, Italy, 3 Pathology Unit, Sant'Orsola-Malpighi
The pathological classification (OMS 2017) of pituitary adenomas distin- Hospital, University of Bologna, Bologna, Italy, 4 Department of
guishes the "typical" pituitary adenomas; pituitary carcinomas whereas Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University
the term of atypical adenoma is no longer recommended nevertheless it of Bologna, Bologna, Italy, 5 Department of Experimental, Diagnostic
remains important to identify them with some criteria including a Ki67 □ and Specialty Medicine, S. Orsola-Malpighi Hospital, University of
3% and a strong nuclear positivity for p53. Bologna, Bologna, Italy
Methods: The aim of this study is to evaluate the histopronotic value of
Ki67 and P53 nuclear staining performed on a series of 42 atypical PA. Background & Objectives: The aim of the study was to analyse the
Results: According to our results, we noted a female predominance clinico-pathological characteristics of the adrenocortical adenomas com-
(80%). bined with myelolipomas.
The age of the patients in our series varies between 16 to 77 years old. The Methods: We identified 10 cases over 222 adrenalectomies collected
most affected age group is between 25 to 40 years old. According to the between 2015 and 2019. For each case we reported: clinical data, macro-
size we note a predominance of macroadenoma (64%). scopic and histological features including Weiss score.
In our series Ki-67 revealed a degree of proliferation ≥3% in 26% of cases Results: Among 10 cases collected, 7 were women; the patients’ age
with a positive p53 in 20% control. ranged from 47 to 69 years (on mean of 62 years). About clinical symp-
Conclusion: The WHO classification (2017) took into account the "risk" toms, 9 cases were functional adenomas (with hyperproduction of gluco-
presented by a pituitary adenoma with regard to recurrence or aggressive- corticoids in 6 cases and aldosterone in 2, mixed secretion in 1).
ness by integrating at the same time the size, the phenotype and the At gross examination, the median size of the nodules was 3.8 cm (from 1.5 to
histological and / or molecular markers essential to a better stratification 10 cm). Almost all nodules were yellowish, mostly with cystic or hemor-
of this type of adenoma. rhagic changes. Microscopically, the tumours were composed of cords and
nests of clear and / or eosinophilic cells which included adipose tissue with
scattered islands of myelopoietic elements. The Weiss Score range was from
E-PS-08-031 1 to 4 (median of 1.5). The median value of Ki-67 was 4.6 (from 2.5 to 5.6).
Rectal neuroendocrine tumour G2 with multiple metastatic lesions Conclusion: In summary, the combination of adrenocortical adenoma
(case report) with myelolipoma is not so rare as reported in literature. In the present
B. Güçlüer1, G. Kir1, T. Soylemez1 study, it occurred mainly in adult females with clinical presentation of
1
Istanbul Medeniyet University, Department of Pathology, Turkey cortisol excess. Moreover, considering the separate embryologic origin of
the adrenal cortex and medulla, these lesions could represent a form of
Background & Objectives: Primary neuroendocrine tumours (NETs) collision tumour.
are common and neuroendocrine carcinomas (NECs) are rarely seen in
the rectum. It is reported that Rectum NETs exhibit different histopatho-
logical features and clinical behaviour than other GIS NETs. A case of E-PS-08-033
NET with a bland morphology showing aggressive clinical behaviour Medullary thyroid carcinoma - giant cell type
was reviewed with current data. S. Loxha1, R. Limani2, O. Blatnik3, B. Gazic4, I. Loxhaj5
1
A 71-year-old man without medical/surgical history presented with lower Institute of Pathology Kosovo, Kosovo, 2 Institute of Pathology
urinary system symptoms and rectal bleeding. Rectal examination and Kosovo, Albania, 3 Institute of Oncology Ljubljana, Slovenia,
4
prostate needle biopsy was unremerkable. Colonoscopic examination re- Institute of Oncology Ljubljana, Slovenia, 5 Institute of Pathology
vealed a 15 mm, polypoid mass in rectum. Colonoscopic biopsy was Kosovo, Kosovo
performed.
Results: The tumour composed of uniform cells, arranged in alveolar Background & Objectives: Medullary thyroid carcinoma is a rare
pattern and with a ribbon-like pattern on microscopy. Tumour cells have agressive tumour of the neuroendocrine origine, that arises from
round nuclei and stippled chromatin. The mitotic count was low and Ki- parafollicular C-cell.
67 proliferation index was 3%. Necrosis was absent. The differential Methods: Case report
diagnosis inclues prostatic adenocarcinoma and NETs. The Results: A 61-year-old woman with surgical spicemen of total thyroid-
immunoprofile of this tumour showed diffuse strong positive staining ectomy and clinical diagnosis tumour glandulae thyroidae. FNAC of the
for Synaptofisin, CD56, PSAP and negative staining for PSA, NKX3.1, patient was malignant. Histopathology confirmed encapsulated nodular
CK7, CK20, CDX2, TTF-1, chromogranin A, calcitonin. These morpho- tumour 7x6.5x3.5cm, showed nests and sheets of cells with moderate to
logical findings and immunohistochemistry results supported a diagnosis abundant cytoplasm, round and oval nuclei, large giant cells with bizarre
of well differentiated NET. Metastatic foci were found in the liver, adrenal nuclei surrounded by dense hyalinized stroma. Mitotic activity, necrosis,
gland and iliac lymph nodes. vascular invasion and calcificts presents. The tumour was limited to thy-
Conclusion: In many organ systems, NETs are graded as G1, G2, or G3 roid capsule. Imunichemistry examination: Calcitonin positive, CEA,
based on mitotic count and/or Ki-67 labeling index, NECs are considered Chromogranin i TTF1 positive.
high grade by definition. This conceptual approach can form the basis for Conclusion: Medullary thyroid carcinoma is a rare and aggressive tu-
the next generation of NEN classifications and will allow more consistent mour, but morbidity and mortality remain high if untreated. It was
Virchows Arch

difficult to diagnose only with H&E examination, but the appearance of Conclusion: Intermediate vascular tumours in the female genital tract can
imunochistochemical biomarkers Calcitonin positive, CEA positive and present with symptoms similar to any gynaecological tumours and can
Chromogranin positive ,has helped us in the final diagnosis. lead to radical surgery. Histopathological examination is obligatory in all
such cases to exclude aggressive high-grade sarcoma.
Sunday, 8 September 2019 – Wednesday, 11 September 2019
E-PS-09 | Gynaecological Pathology
E-PS-09-003
Microcystic stromal tumour of the ovary: a report of 2 cases
E-PS-09-001 C.Y. Chow1, G. Mihir2, S.H. Chew2, Y.C. Yeo2
1
Malignant mixed sex cord stromal cell tumour with unusual histo- Singapore General Hospital, Singapore, 2 KK Women's and Children's
logical appearance: a case report Hospital, Singapore
R. Shi1, C.Y. Chow1,2, M.A. Gudi2, S.H. Chew2, Y.C. Yeo2
1
Singapore General Hospital, Singapore, 2 KK Women's and Children's Background & Objectives: Ovarian microcystic stromal tumour is an
Hospital, Singapore uncommon neoplasm which was classified in the 2014 WHO
Classification as a pure stromal tumour within the category of ovar-
ian sex cord-stromal tumours. This entity was originally described
Background & Objectives: Sex cord-stromal tumours (SCST) are uncom-
as an ovarian neoplasm exhibiting a distinctive triad of histologic
mon primary ovarian neoplasms. Occasionally a sex cord-stromal tumour
features with microcysts, solid cellular regions and hyalinized fi-
lacks definitive characteristics of any specific tumour type and may be clas-
sified as “SCST, NOS (Not Otherwise Specified)”. Here, we report a malig- brous stroma. This neoplasm presents as a non-functioning pelvic
nant SCST, NOS, with unusual histological features. Molecular tests on re- mass. In this study, we report two cases of microcystic stromal
cently discovered gene profiles for SCST were performed. tumour of the ovary.
Methods: The first case is of a 49-year-old lady who presented with
Methods: A 68-year-old lady presented with pressure symptoms.
acute abdominal pain and CT scan revealed a torted right ovarian
Ultrasound showed a large hypoechoic abdominopelvic mass with lobu-
tumour. She underwent emergency right salpingo-oophorectomy.
lated appearance, coarse calcification and cystic areas measuring 14.3 x
Macroscopic examination showed a 14.5cm solid-cystic tumour
11.1 x 7.9cm. Differential diagnoses included pedunculated fibroid and
with large areas of haemorrhagic infarction. The second case is of
ovarian tumour.
a 66-year-old lady who presented with postmenopausal bleed, inci-
Results: Microscopically, the ovarian tumour showed a heterogeneous dentally found to have a right ovarian complex mass on ultrasound.
morphology. Focally, areas of fibroma were admixed with areas compris- A 12cm solid-cystic right ovarian tumour was resected in the sub-
ing fascicles of markedly atypical malignant spindle cells with brisk mi- sequent operation.
totic activity and necrosis resembling fibrosarcoma. Other areas show Results: On microscopy, both tumours showed a multinodular pat-
fibromatous background with clusters and sheets of cells showing nuclear tern, comprising a monotonous population of tumour cells ar-
grooves resembling fibromatous AGCT. FOXL2, TERT and DICER2 ranged in microcystic architecture. The tumour cells had bland
gene mutations were not demonstrated. The differential diagnoses were cytologic features and stained for CD10, WT1 and β catenin,
between sarcomatous transformation of an adult granulosa cell tumour but were negative for common sex cord markers such as inhibin
and a malignant SCST, NOS. and calretinin. Mutational analysis of both cases revealed a mis-
Conclusion: High grade malignant sex cord-stromal tumours are rare and sense point mutation in exon 3 of CTNNB1, as reported in the
challenging to classify. Recently, several gene mutations have been iden- literature. There was no recurrence at the last follow up date for
tified which may help in classification. However, in our case, these mu- both cases.
tations were not detected. This may reflect the complex molecular path- Conclusion: Ovarian microcystic stromal tumours are challenging to
ogenesis of these tumours, especially when they undergo malignant trans- recognize due to their rarity and microcystic appearance that may raise
formation. a broad differential diagnosis. The characteristic immunophenotype and
CTNNB1 mutation could serve as useful ancillary tests. It is important to
be cognizant of this entity, as most of the cases are reported to have a
E-PS-09-002 benign clinical course to date.
Intermediate vascular tumours of the female genital tract
O. Oluwole1
1
University of Abuja, Nigeria E-PS-09-005
Low grade endometrial stromal sarcoma - case report
Background & Objectives: Vascular tumours of intermediate malignan- A. Mărcuță1, M. Aschie2,1, G.C. Cozaru1,2, A. Mitroi2,1, C. Brinzan2,1,
cy encompass a broad range of histologic entities. They are characterised T.S. Nitu1, R.D. Sora1
clinically by having a high risk of local recurrence and limited risk of 1
Pathology Department, Emergency County Clinical Hospital of
regional or distant metastasis. Vascular tumours of intermediate malig- Constanta, Romania, 2 CEDMOG, "Ovidius" University of Constanta,
nancy frequently presented in the skin often with diagnostic difficulty and Romania
are very rare in the female genital tract.
Objective was to analyse the distribution of intermediate vascular tu- Background & Objectives: Endometrial stromal sarcomas (ESS) are
mours the female genital tract. rare malignant tumours accounting for about 0.2% of all genital tract
Methods: Materials are derived from private pathology consultations and malignancies, so the majority of information available in literature is
review of the literature. based on small series or case reports. The origin and biology of stromal
Results: Three patients aged (27, 33 and 35) years respectively. The sites sarcomas are poorly understood and immunohistochemistry will help in
of the tumour were two in the ovaries (right and left) and one in the the detection of tumour markers specific for ESS.
cervix. The tumour was diagnosed based on routine Haematoxylin and We report a case of low-grade ESS in a 32-year-old woman who present-
Eosin stain as immunohistochemistry facility is not available in our cen- ed with a four-month history of excessive bleeding per vagina.
ter at the time of diagnosis. All the patients had surgical treatment and Methods: The histopathological examination of the endometrial curet-
there was no recurrence after a year of follow-up by the attending tage and cervical biopsy and immunohistochemistry markers (asdesmin,
surgeon. h-caldesmon, oxytocin receptors, CD10, and inhibin which were useful in
 Virchows Arch

distinguishing cellular leiomyoma) showed an endometrial stromal sar- stroma. The current WHO classification acknowledges four categories
coma. The sample were cytogenetically analysed and the result showed within the endometrial stromal family of tumours namely, endometrial
an abnormal karyotype: 46,XX,t(10;17)(q22;p13)[18]/46,XX[5]. Total stromal nodule, low grade endometrial stromal sarcoma (LG-ESS), high
abdominal hysterectomy, with bilateral salpingo-oophorectomy, grade endometrial stromal sarcoma (HG-ESS) and undifferentiated uter-
omentectomy and elective pelvic lymphadenectomy were then performed ine sarcoma (UUS). We review three cases of endometrial stromal
as a second radical surgical approach. tumours.
Results: Endometrial stromal sarcomas are uncommon and their differ- Methods: Three cases of endometrial stromal tumour diagnosed over a 1-
ential diagnosis from typical submucosal uterine myomas or benign en- year period (2017-2018) were retrieved from departmental archives.
dometrial polyps could be difficult. Our patient presented at 32 years, Blocks were stained with H&E. Immunohistochemistry was performed
which is a rarity in itself. The hysteroscopic features of uterine sarcomas with three antibodies used namely CD 10, ER and PR.
are often similar to those of endometrial polyps or submucosal myomas. Results: The patient’s ages were 48, 50 and 65 years. Diagnoses was
It is a diagnosis that should only be made after excluding other high-grade endometrial stromal nodule in the 48-year-old, LG-ESS in the 50 years
tumours with a sarcomatous component. old and HG-ESS in the 65 year old patient. Endometrial stromal nodule
Conclusion: Total abdominal hysterectomy, bilateral salpingo- shows a circumscribe lesion composed of uniform oval small cells with
oopherectomy with pelvic lymphadenectomy is the optimal treatment in scanty cytoplasm whorl around arteries. LG-ESS shows areas of
cases of endometrial stromal sarcomas. myometrial invasion and mitosis was less than 3. HG-ESS showed ares
of necrosis, lymphovascular invasion. All were positive for CD10, PR
Research supported by CEDMOG, Ovidius University of Constanta, and ER stains.
POS CCE 2.21. Project, (ID 1844, SMIS 48750). Conclusion: Endometrial stromal tumours are rare in our society. More
studies need to be done to fully understand the mutations and biologic
behaviour of these tumours.
E-PS-09-006
Ovarian Leydig cell hyperplasia - a rare cause of virilisation
T.M. Costa1, C. Albuquerque1, R. Sampaio1 E-PS-09-008
1
Centro Hospitalar Lisboa Ocidental, Portugal Classical gonadoblastoma presenting as huge unilateral ovarian
mass: an unusual presentation of a germ cell- sex cord-stromal
Background & Objectives: There are two main causes of female tumour
hyperandrogenism: ovarian or adrenal pathology. We aim to report a rare K. Adoke1, A. Umar Adoke2
1
case of ovarian Leydig cell hyperplasia causing hyperandrogenism and Federal Medical centre Birnin Kebbi, Nigeria, 2 Usmanu Danfodio
consequent virilization of a postmenopausal woman. To the best of our University Teaching Hospital, Nigeria
knowledge there are 18 reported cases of this entity, and apart from one,
all associated with masculinization symptoms. Background & Objectives: Gonadoblastoma was first described by
Methods: A 60-year-old woman presented increasing hirsutism and an- Scully in 1953 is a mixture of germ cell tumour and sex-cord stromal
drogynous alopecia. Her past medical history included breast carcinoma tumour. It usually occurs in individuals with abnormal sexual develop-
at age 39, for which she underwent surgery, chemo, radio and ment, indeterminate gonads with 80% been phenotypically normal wom-
hormonotherapy, with consequent premature menopause at age of 42. en and 20% phenotypical men with undescended testicles. About 40% are
The laboratory work-up showed hyperandrogenism with total serum tes- bilateral. It is believed to be a precursor of germinoma. We present a rare
tosterone 85 ng/dL (normal range 2.9- 40.8 ng/dL). After exclusion of case of gonadoblastoma in a phenotypically normal female who present-
adrenal causes, a virilizing ovarian tumour was assumed and the patient ed with large unilateral right ovarian mass.
underwent laparoscopic bilateral oophorectomy. Methods: A 20-year-old female who was not yet married presented to the
Results: On gross pathological examination without particular findings. gynaecology clinic with abdominal swelling for 10 years. She was ac-
Histologically in both ovaries at the hilar region we observed ill-defined cused by her parents of having been impregnated by her boyfriend when
scattered small nodules of cells. These had a granular eosinophilic cyto- they noticed sudden increase in the abdominal swelling in the last five
plasm, round uniform nucleus and distinct nucleolus, consistent with months. Ultrasound reveal unilateral ovarian cyst measuring
Leydig cell hyperplasia. The distinction between Leydig cell hyperplasia 37x32x17cm. Cyst was excised and sent for histology.
and tumour is based on the pattern and size of the nodules. Two months Results: Gross examination shows a huge cystic specimen measuring
postoperatively, the serum testosterone was undetectable (<2.5 ng/dL), 35x30x15cm, it contains 10 liters of clear fluid, the cyst lining showing
and there was a clinical improvement. coarse granular pale surface. Histology shows islands of germ cells
Conclusion: Besides alerting for other causes of virilization, we aim to admixed with sex cord stromal elements surrounded by hyalinized base-
emphasize the importance of differential diagnosis between two rare en- ment material and few calcifications. No germinoma focus was seen.
tities: Leydig Cell hyperplasia that is curative with oophorectomy, and Conclusion: Classical gonadoblastoma can present as a cystic ovarian
Leydig Cell tumour that may be associated with DICER1 syndrome, and mass, careful follow up of patients is necessary as the germ cell compo-
its clinical behavior is highly correlated with the histologic grade. nent may overgrow the stromal component resulting in dysgerminoma.

E-PS-09-007 E-PS-09-009
Endometrial stromal tumours: a clinicopathological and immunohis- Synchronous mature teratoma and Sertoli-Leydig cell tumour in the
tochemical review of three cases in a resource poor setting same ovary
K. Adoke1, Y. Iliyasu2, A. Umar Adoke3 S. Aviel-Ronen1, R. Barenboym2, B. Czernobilsky3
1
Federal Medical centre Birnin Kebbi, Nigeria, 2 Ahmadu Bello 1
Department of Pathology, Sheba Medical Center, Tel-Hashomer, Israel,
University Zaria Nigeria, Nigeria, 3 Usmanu Danfodio University 2
Gynaecology Department, Galilee Medical Center, Nahariya, Israel,
3
Teaching Hospital, Nigeria Patho-Lab Diagnostics, Ness Ziona, Israel

Background & Objectives: Endometrial stromal tumours (EST) were Background & Objectives: Sertoli-Leydig cell tumour (SLCT) is a rare
first described by Norris and taylor as a distinct group of mesenchymal ovarian tumour, comprising less than 0.5% of ovarian neoplasms. Mature
neoplasms of the uterus with morphological resemblance to endometrial teratoma accounts for 20% of ovarian tumours. Both tumours have a wide
Virchows Arch

age distribution but usually appear in the reproductive years. Their syn- E-PS-09-011
chronous coexistence has been reported in less than a handful case re- Endometriosis in the abdomen and pelvis
ports. Here we describe a rare case of ovary containing both mature A. Ilic1,2, M. Panjkovic1, T. Lakic1,2, M. Zivojinov1,2, Z. Vrekic2, J. Ilic
teratoma and Sertoli-Leydig cell tumour (SLCT). Sabo1,2
1
Methods: The medical records, imaging tests and pathological findings University of Novi Sad, Faculty of Medicine, Serbia, 2 Clinical Center
of a 77 years old patient have been studied and are presented. The patient of Vojvodina, Novi Sad, Center for Pathology and Histology, Serbia,
was under ultrasonographic follow-up for about a year due to a small right
ovarian cyst, 4 cm in largest dimension. Her blood levels of CA125, Background & Objectives: Endometriosis is the condition characterised
CA15.3, CA19.9 and CEA were within normal limit. Both her ovaries by the presence of endometrial tissue outside the uterine cavity. It is
were removed laparoscopically. predominantly found in ovaries, uterosacral and big ligament, Fallopian
Results: The right ovary contained a sebaceous material filled cyst tubes and intestinal tract. Intestinal endometriosis prevails in
with some solid areas, representing a typical mature cystic terato- rectosigmoid junction and small bowel, usually affecting subserosa and
ma. A separate, 1.2 cm sized well circumscribed lesion, was at- serosa.
tached. The lesion contained closely packed tubules, surrounded We analysed available data of patohistological verified endometriosis in
by stroma. The tubule columnar cells had bland nuclei, Sertoli intestinal tract (age, location, clinical and patohistological diagnosis, oth-
cells morphology and were CK and NSE positive while ER and er diseases and conditions) and compared results with results from other
PAX8 negative. Inhibin and calretinin stains enhanced the stromal scientific works.
Leydig cells surrounding the tubules. Well differentiated SLCT Methods: Retrospective study contained 16 patient with confirmed
was diagnosed. patohistological diagnosis of endometriosis in 5 years. Data were present-
Conclusion: Theoretically, well differentiated Sertoli-Leydig cell tis- ed in table and charts. Patohistological samples were photographed and
sue associated with mature teratoma can reflect differentiation of the microphotos were described and enclosed with charts.
teratoma into testicular tissue. Although this possibility cannot be Results: The highest incidence of endometriosis (56%) is among the
excluded, since the Sertoli-Leydig cell tissue was attached to the patients between age 31-40, followed by group of patients between age
teratoma and not within it, we favor the interpretation of a rare syn- 41-50 with percentage frequency of 25% . When it comes to the most
chronous occurrence of mature cystic teratoma and SLCT in the same common sites of endometriosis, we talk about anterior abdominal wall
ovary. (33%) and ovaries (28%), while the intestinal tract is affected in less than
5% of cases. In most cases clinical diagnosis does not match
patohistological and endometriosis is not followed by additional diseases
E-PS-09-010 or conditions.
A voluminous well differentiated neuroendocrine neoplasm of the Conclusion: Our results concerning age are in line with previous re-
right ovary, with uncertain biological behaviour. search. On the other hand, there is discrepancy in regard with localization.
E. Koniaris1, E. Moula1, K. Tsiardis1, C. Gkogkou1, G. Kafiri1 According to our data, endometriosis predominantly occurs in fibrous and
1
"Hippokratio" General Hospital of Athens, Greece fatty tissue in the front abdominal wall.

Background & Objectives: Ggynaecological neuroendocrine tumours

(NET) are exceptionally rare lesions, with only very few reported cases in E-PS-09-012
the international literature, accounting for approximately less than 0,1% Glassy cell carcinoma spreading on a prolapsed leiomyoma with
of all ovarian tumours. They are a heterogenous group of separate entities, marked lymphatic invasion: case report
which all of them share a common feature, the expression of endocrine S. Nagase1, K. Ogura1, K. Ashizawa1, M. Fukunaga2, T. Matsumoto1
1
differentiation potential. NETs can occur in pure forms or maybe associ- Juntendo University Nerima Hospital, Department of Diagnostic
ated with other tumours and cases arising in mature cystic teratomas, have Pathology, Japan, 2 Department of Pathology, Shin-yurigaoka General
been described. Hospital, Japan
Methods: A 51-year-old patient referred to our hospital with a mass in the
right ovary. She underwent hysterectomy and bilateral oophorectomy. We Background & Objectives: Glassy cell carcinoma is a rare variant of
received uterus measuring 11X8,5X6cm, left ovary m.d.: 3,2cm and right poorly differentiated adenosquamous carcinoma and is considered to
ovary measuring 14X12,5X11cm, with was completely infiltrated by have poor prognosis. We report a case of 62-year-old nulliparous
whitish in hue, solid mass, with multiple cysts, mainly in central location. Japanese woman who presented with 73mm vaginal mass and abnormal
Immunohistochemistry: CD56 (+), Chromogranin (+), NSE (+), vaginal bleeding. The mass was considered as a prolapsed leiomyoma,
Synaptophysin (+/-), AE1 (+). PLAP (-), Inhibin (-), S100 (-), but since a few clusters of adenocarcinoma with serous-like morphology
Calcitonin (-), SMA (-), Desmin (-), c-kit (-), ki67 (<3%). was shown in cytology and biopsy specimens, total hysterectomy, bilat-
Results: Histologicaly, the tumour cells had a monotonous appear- eral salpingo-oophorectomy, and pelvic lymph node dissection were
ance with round nuclei, without nucleoli and an eosinophilic cyto- performed.
plasm, without atypia and sparse mitosis. The neoplastic cells were Methods: We recognized a poorly differentiated carcinoma spreading on
arranged in bands, islands, trabecules and at places in microrossettes, the surface of a pedunculated leiomyoma evolving from the uterine isth-
as well as with few cystic spaces. Although hemorrhagic infiltrations mus. The tumour cells had enlarged nuclei and nucleoli with glassy eo-
were found, necrosis was not observed. The presence of perivascular sinophilic cytoplasm reminiscent of glassy cell carcinoma. Moreover,
infiltration, the vascular emboli, the cystic degeneration and the size carcinoma displayed prominent lymphatic invasion inside the leiomyoma
of the tumour, suggest a degree of uncertain biological behavior re- although metastasis was not detected in the dissected lymph nodes. Based
lated to the tumour. on the pathological findings, she underwent postoperative adjuvant
Conclusion: NETs are rare germ cell tumours, and many scientists clas- chemotherapy.
sify them as teratomas with a predominance of neuroendocrine features, Results: Six-months after the operation, she was admitted to our
mainly in peri- or postmenopausal women, incidentally, found usually hospital due to bowel obstruction and malignant pleural effusion.
unilaterally, slow growing and diagnosed in early stages. Four distinct Despite the treatment, her status deteriorated and died one month
histological subtypes have been described: insular (most common), tra- after the admission. An autopsy revealed that her death was due to
becular, mucinous and strumal. A third of the patients might experience peritonitis carcinomatosa of glassy cell carcinoma and subsequent
carcinoid syndrome symptoms. septic shock.
 Virchows Arch

Conclusion: This case exhibits an unusual infiltrating pattern of glassy Methods: We report the case of a 31-year-old woman admitted at the
cell carcinoma spreading on a prolapsed leiomyoma with marked lym- Emergency University Hospital in Bucharest due to severe abdominal
phatic invasion, and as far as we know, this is the first case to be reported. pain. Ultrasound evaluation revealed a large uterine mass with 17 cm in
its longest axis and a synchronous 2 cm cystic lesion of the left ovary.
Serum tumour markers were normal. The patient underwent a total hys-
E-PS-09-013 terectomy with left salpingo-oophorectomy.
Immunohistochemical phenotype of decidual cells during ectopic Results: Gross examination of the surgically resected specimen revealed
pregnancy a well-defined, intramural mass with myxoid changes and focal hemor-
J. Krylova1,2, A. Drobintseva1, I. Kvetnoy1, V. Polyakova1, V. Korsak3 rhagic areas located on the posterior wall of the uterine corpus. The
1
D.O. Ott. Research Institute of Obstetrics, Gynaecology and ovarian mass was highly suggestive for endometrioma. Microscopic ex-
Reproductology, Russia, 2 Pavlov First Saint Petersburg State Medical amination revealed an incidental mixed capillary-cavernous hemangio-
University, Russia, 3 International Centre for Reproductive Medicine, ma. Immunohistochemical staining showed strong immunoreactivity for
ICRM, Russia CD31 and CD34. Thus, the final diagnosis of primary ovarian hemangi-
oma was established. The uterine mass was represented by a leiomyoma
Background & Objectives: The process of decidualization occurs as with myxoid changes.
a result of the reaction of fibroblasts of connective tissue to the Conclusion: Although an uncommon entity, awareness of ovarian hem-
action of hormones, prostaglandins, cytokines and various growth angioma's particular and diverse clinical presentation as well as its poten-
factors. Since fibroblasts are essential components of any stroma, it tial to imitate more common lesions such as endometriosis and other
can be assumed that a decidual reaction in case of fertilization can ovarian neoplasms is extremely important. Surgical removal of the in-
take place in any organ. volved areas and a careful clinical examination is advised because it is
Aim of the study: to determine the clinical and morphological features of known that these lesions may occur in a syndromic context.
deciduous cells in ectopic pregnancy.
Methods: Material was divided in two groups: I-decidual tissue revealed
by pathohistological examination of ectopic pregnancies (6-8 weeks of E-PS-09-015
gestation), II-decidual endometrial tissue of abortive material of the same Intravascular leiomyomatosis: a case report
gestation period. M. Mrcela1, D. Milojkovic2, I. Stefanac3
1
Methods. Staining with hematoxylin and eosin was carried out to Medicinski fakultet Osijek, Croatia, 2 KBC Osijek, Croatia, 3 Primary
determine the timing of gestation and assess inflammatory changes. Health Care Center Osijek, Croatia
Immunohistochemical reactions were performed with antibodies to
Vimentin (DAKO, Denmark), LIF (Abcam, UK), PR (DAKO, Background & Objectives: Intravenous leiomyomatosis is a rare occur-
Denmark) rence of histologically benign smooth muscle proliferation venous
Results: Microscopic analysis of the I group in the omentum and in spaces.
the ovarian cortex determined the foci of decidual transformation as Methods: A 46-year-old patient underwent hysterectomy with bilateral
an enlarged polygonal cells with eosinophilic, vacuolated cytoplasm adnexectomy due to clinical suspicion of ovarian tumour. Tumour masses
and insignificant infiltration of lymphocytes. Immunohistochemical were located in the area of the parametrium, they looked solid and cystic,
study revealed a positive staining of the foci of decidualization of the solid parts were nodular, whorled appearance on the cut surface, with
the omentum with Vimentin, PR, LIF. The level of expression of all a longer diameter of 7 and 4,5 cm.
markers, when compared with the decidual endometrium, differed Results: Worm-like smooth muscle proliferations were found in vascular
insignificantly, and was expressed mainly in the focal response to spaces lined with vascular endothelium positive for CD31 and CD34 and
LIF. negative for D2-40 both in myometrium and veins of the parametrium, where
Conclusion: The omentum cells are positive to PR and can be trans- the biggest tumour masses were found. Vascular endothelial layer also was
formed under influence of progesterone into decidia, with increasing detected on the surface of smooth muscle intravascular proliferations.
concentration LIF, but not all cells with a decadal transformation Conclusion: This is an illustration of unusual smooth muscle neoplasm
were positive for this cytokine. What makes it possible to think with quasi malignant intravascular growrh. At this point, four years after
about the different directions of differentiation of these cells and surgery, our patient is alive and healthy.
their functions.

E-PS-09-016
E-PS-09-014 Unexpected diagnosis in bilateral ovarian tumour
Primary ovarian haemangioma - a relatively common entity inciden- L. Lozneanu1, R.A. Balan2, S.E. Giusca2, R.E. Avadanei2, I.D. Caruntu1,
tally discovered in an extremely unusual site C. Amalinei1, A. Grigoras2
A. Dumitru1, T. Georgescu1,2, C. Gavan3, O. Munteanu4, M. Sajin5,6,7 1
"Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania,
1 2
Department of Pathology, "Carol Davila" University of Medicine and Department of Morphofunctional Sciences I-Histology, "Grigore T.
Pharmacy, Bucharest, Romania, 2 Department of Pathology, Emergency Popa" University of Medicine and Pharmacy, Iasi, Romania
University Hospital Bucharest, Romania, 3 4th Department of General
Surgery, Emergency University Hospital Bucharest, Romania, Background & Objectives: Primary ovarian hydatid disease (HD) is a
4
Obstetrics-Gynaecology Department of the University Emergency rare distinct entity, commonly involving liver, lung, kidney, spleen,
Hospital Bucharest, Romania, 5 SUUB, Romania, 6 UMF Carol Davila, bones, brain, and thyroid gland. HD is rarely diagnosed in pelvic organs,
Romania, 7 European Society of Pathology, Romania such as ovaries and genital tract.
We report a postmenopausal female patient hospitalized for a large left
Background & Objectives: Ovarian hemangiomas are very rare benign ovarian tumour which had been slowly developed, along with a right
tumours of the female genital tract with less than 60 reported cases in the ovary solid ovarian tumour, being suspected of bilateral ovarian
scientific literature, the majority being described as isolated case reports malignancy.
of unusual clinical presentations or particular morphologic findings. Methods: Routine hematoxylin and eosin, along with PAS staining, and
These neoplasms occur in both adults and children with the age ranging immunohistochemistry, for CK7, CK20, Ki-67, and ER have been
from infancy to 81 years. performed.
Virchows Arch

Results: The gross specimen of right ovary showed a smooth surface, (40) and diffuse toxic goiter (30)) was carried out with help of
with pasty consistency and translucent bands, containing a thick mucoid Scanning Electron Microscopy with emental analysis and atomic force
material. Microscopy showed laminated eosinophilic membrane, microscopy.
pericystic sclerosis, collection of eosinophils, along with focal giant cell Results: It was revealed that the square of vessels at pathology was less
reaction, being diagnosed as a hydatid cyst. The left ovary specimen had than in control group, especially at diabetes mellitus and hypothyroidism.
an intact outer surface, exhibited a multilocular cystic appearance, with Folding of endothelium was significantly violates at diabetes mellitus and
few inner papillae, and mucinous fluid content. The microscopic exami- diffuse toxic goiter. The number of normocytes was decreased to 40,0
nation along with immunohistochemistry features diagnosed a concomi- ±4,0 % at diabetes mellitus, to 42,0±5,0 % at diffuse toxic goiter, to 55,0
tant mucinous borderline tumour. ±3,0 % at hypothyroidism and to 60,0±3,0 % at gestational diabetes(84,0
Conclusion: The ovarian location of echinococcosis is extremely rare but ±4,0% in control group). Alternative processes in stroma prevailed at
it should still be considered in any differential diagnosis of a cystic lesion, diabetes and diffuse toxic goiter.
while it does not exclude a synchronous ovarian tumour. The current case Conclusion: SEM and AFM are reliable and resultative methods for
highlights the necessity of a better screening of HD in endemic areas. research of tissues at pathology of pregnant.

E-PS-09-017 E-PS-09-019
Clinicopathological analysis of incidentally detected blue nevi of the Synchronous case of the primary neuroendocrine cancer of fallopian
uterine cervix in biopsy or curettage specimens. A report of 7 cases tube and serous papillary cancer of ovary
N. Basheska1, B. Ognenoska-Jankovska1 N. Hyriavenko1, M. Lyndin1, S. Vladyslav1, O. Kravtsova2, D. Sumtsov2,
1
Department of Histopathology and Clinical Cytology, University Clinic D. Hyriavenko1, A. Romaniuk1
1
of Radiotherapy and Oncology, Ss Cyril and Methodius University Sumy State University, Medical Institute, Pathology Department, Ukraine,
2
Faculty of Medicine, Republic of North Macedonia Sumy Regional Clinical Oncology Center, Sumy, Ukraine

Background & Objectives: Blue nevi (BN) of the uterine cervix (UC) Background & Objectives: Neuroendocrine tumours commonly occur
are rare incidental lesions; they are often found in hysterectomy speci- in the gastrointestinal tract and lungs. They rarely were found in the
mens from middle-aged women, or rarely in specimens obtained during genital organs. There are a few data about this neoplasia in the fallopian
more conservative diagnostic procedures (e.g. biopsy, curettage). The tubes, which is accidentally identified during the morphological study.
objective of our study was to analyse the clinicopathological features of The aim of our investigation was to demonstrate the case of the primary
7 incidentally detected cases of the BN of the UC in biopsy or curettage neuroendocrine cancer of the fallopian tube in combination with the se-
specimens. rous papillary cancer of the ovary.
Methods: Among a total of 60 BN of the UC diagnosed on operative and Methods: The histological and immunohistochemical (СК7, СК20,
biopsy specimens in our Department between 2000-2019, in 7 (7/60, СА125, ER, chromogranin А, CD56, CDX2, Ki-67) investigations were
11.7%) cases BN were found in biopsy or curettage specimens that had conducted for the study of the molecular peculiarities of the fallopian tube
been taken for an examination of a clinically or cytologically suspicious and ovary tumours.
cervical lesion (3/7, 42.9%) or a dysfunctional uterine bleeding (4/7, Results: The tumour growth was found in the fallopian tube wall,
57.1%), respectively. The mean age of the patients was 44 years (range, which is presented by trabecular structures. Immunohistochemistry
29-57 years). In addition to routine hematoxylin&eosin, histochemical showed that it was negative for СК7, СК20, СА125, ER, CDX2
and immunohistochemical stainings were also performed. and strong positive for chromogranin A and CD56. Ki-67 expres-
Results: Histologically, all cases showed loose aggregates of pigmented, sion was observed in 3% of cells. In the ovary, the tumour with
spindle-shaped, dendritic or nevoid, epithelioid cells in the superficial the formations of papillary structures, cellular atypia, as well as
stroma in one (4/7, 57.1%) or >2 fragments of cervical mucosa (3/7, single psammoma bodies was present. It was CK7, CK20,
42.9%). The lesions ranged in size from 0.5 to 6mm (mean, 2.4mm), CA125, ER positive and didn’t express chromogranin A, CD56
while their thickness ranged between 0.5-4mm (mean, 1.5mm). In one and CDX2.
case the BN was presenting as an endocervical polyp. The pigmented Conclusion: Finally, the following diagnosis was made: low-grade
cells in all tested cases were positive for melanin (Fontana-Masson), neuroendocrine cancer of the fallopian tube and high-grade serous
S100, Melan-A, as well as for HMB45 in 3 cases. papillary cancer of the ovary. This case demonstrates the possi-
Conclusion: Although the BN of the UC seem to be lesions of low bility of the occurrence of the primary neuroendocrine cancer in
clinical significance, they require careful differential diagnosis with other the fallopian tube in combination with the serous papillary ovar-
pigmented lesions including malignant melanoma, especially because ian carcinoma.
they are rarely detected and might easily be missed or misinterpreted in
scanty endocervical curettage or cervical biopsy specimens due to their
small size, more frequent endocervical localization and occasional dis- E-PS-09-021
crete findings. Juvenile granulosa cell tumour or adult granulosa cell tumour - a
diagnostic dilemma
M. Kirigin1
1
E-PS-09-018 Department of Pathology and Cytology, Sestre Milosrdnice University
The new approaches in research of pathomorphological aspects of Hospital Center, Croatia
endocrinopathies in obstetrics
T. Pavlova1, A. Selivanova1, A. Kaplin1, L. Zemlianskaia1, E. Malutina1 Background & Objectives: Juvenile granulosa cell tumour (JGCT)
1
Belgorod State University, Russia mostly occurs in young women, with wide differential diagnosis includ-
ing small cell carcinoma of hypercalcemic type, desmoplastic small round
Background & Objectives: The research of system mother- placentha- cell tumour, germ cell tumours and others; however, JGCT is most com-
fetus in caases of endocrinopathies are still actual questions. monly confused with AGCT.
Methods: The research of bioptates of uterus( endometrium, Methods: The ultrasound in a 16 year old girl with irregular cycles
miometrium), placentha, umbilical cord of women with diabetes mellitus revealed a 12 cm cyst of the right ovary. The cyst was extirpated, sparing
type 1(25), gestational diabetes (30), thyroid pathology( hypotheriosis the ovary.
 Virchows Arch

Results: Grossly, the cyst was morselated in 2 to 5 cm fragments, with was a nodular image on the right lateral wall of the uterus, suggestive of a
0,5 cm thick extremely firm smooth wall. Microscopically, the wall was firm polyp, with the size of approximately 1.2 cm. The second patient is 41
fibrous tissue containing cords and trabeculae of small, relatively uniform years old, at the 40th week of gestation, with a subserosal nodule, mea-
cells with some larger cells with clear cytoplasms, showing up to 8 mitoses/ suring 5.3 cm, found during cesarean section.
10HPF. Immunohistochemistry revealed negativity for epithelial, muscle, Methods: We used our two cases to review the current literature on the
germ cell, lymphocytic and neuroendocrine markers. There was strong pos- morphological, immunohistochemical and clinical behavior aspects of uterine
itivity for vimentin, CD99 and CD56. Inhibin and calretitin were positive myofibroblastic tumours, an uncommon entity in the uterus, in addition to
only in larger cells. Reticulin fibers encircled groups of tumour cells. The emphasizing the importance of its differential diagnosis with other entities,
conclusion was that characteristics fit the diagnosis of luteinized granulosa especially leiomyosarcoma and endometrial stromal sarcoma.
cell tumour. After salpingooophorectomy about 20 samples, 0.5 to 5 cm Results: Both lesions were resected and showed, at the macroscopy, white-
were received. Cut surface of larger samples was yellowish white with gray tissue, sometimes elastic, sometimes gelatinous. Histopathological exam-
hemorrhage. Microscopically, tumour tissue showed macrofollicular and ination was characterised by bundles of spindle-shaped cells with nuclei con-
solid pattern. The immunohistochemical characteristics were the same as taining inconspicuous nucleoli, sometimes grouped in storiform arrangements,
at first biopsy. Some solid areas contained 40 mitoses/10HPF with prolifer- supported by predominantly myxoid stroma with prominent fine vascular
ative activity up to 50%. Small area showed classic AGCT morphology. tissue and a variable inflammatory infiltrate. The neoplasia did not present
Conclusion: JGCT and AGCT share some morphologic characteristics, with necrosis or significant mitotic activity. In the immunohistochemical
and diagnostic difficulty may result when JGCT contains elements of study, the neoplastic cells were positive for ALK-1, HHF-35 and negative
AGCT, which was the case in our patient. for p53 and p16.
Conclusion: The IMT is considered a rare tumour of intermediate biological
behavior with a small proportion of cases being able to recur or metastasize
E-PS-09-022 and cause death. The frequent positivity for ALK has helped in the differential
Immunohistochemical study of p16ink4α, Ki67 in combination with diagnosis with other mesenchymal tumours, as well as offering new therapies
the study of the expression of miR-22, miR-92a and methylation of with tyrosine kinase inhibitors for those with aggressive behavior.
the promoter region of the WIF1 gene in the diagnosis of SIL and
cervical squamous cell carcinoma
E. Kogan1, T. Demura1, G. Bajramova2, V. Chernova2, L. Fajzullin2, N. E-PS-09-024
Fajzullina2, V. Kiselev2 Overexpression of ephrin receptor A2 in the ectopic endometrium of
1
First Moscow State Medical University (Sechenov University), Russia, patients with deep infiltrative endometriosis
2
National Medical Research Center for Obstetrics, Gynaecology and A. Shchegolev1, S. Muftaydinova1, N. Fayzullina1, N. Buralkina1, L.
Perinatology named after Academician V.I.Kulakov, Russia Fayzullin1, V. Chuprynin1
1
NMRCOGP, Russia
Background & Objectives: The purpose of the study is a comprehensive
analyses of clinical, morphological, immunocytochemical data in combi- Background & Objectives: Deepinfiltrativeendometriosis (DIE)
nation with changes in epigenetic markers in the diagnosis of SIL and ischaracterised by the invasion of endometriosis lesions in tissues and
squamous cell carcinoma of the cervix uterus. organs to a depth of over 5 mm and high proliferation. Ephrin receptor
Methods: The study included 101 patients aged 21-49 years. Group 1 - 31 A2 (EphA2) has been demonstrated to critically regulate tumour cell
patients with LSIL, group 2 - 26 patients with HSIL, group 3 - 12 patients growth, migration and invasiveness.
with cervical cancer (SCC), group 4 - 32 patients with NILM. Liquid-based The aim of this work was a comparative analysis of the expression level
cytology conducted with immunocytochemical determination p16ink4α, of the EphA2 receptor in the ectopic endometrium of patients with deep
Ki67 (DakoCytomation), histological and immunohistochemical examination infiltrative endometriosis and endometrial carcinoma.
of biopsies material, HPV - 21 type virus genotyping by means of RT-PCR, Methods: All material from 22 women aged 28-45 years were studied:
determination of the expression level of miR-22, miR-92a and miR25 by 4 cases of deep infiltrative endometriosis, 9 - endometrial carcinoma and
PCR and methylation status of the gene WIF1 bisulfite sequencing method. 9 - endometrium of healthy women (4 - in the secretory phase and 5 - in
Results: It has been established that the complex use of liquid cytology, the proliferative phase). Immunohistochemical analysis with antibodies
the double staining method p16ink4α / Ki67 and HPV tests to EphA2 (1:100, сlone SP169, Abcam, GB) was done to detect receptor
qualitatively,methylation level of WIF1 and miR-92a increase the effec- expression. The results of staining of the glandular cells in the ectopic or
tiveness of early diagnosis of SIL and SCC. eutopic endometrium were performed on a 4-point scale.
Conclusion: Considering our results, a comprehensive study of p16ink4α, Results: Eph A2 receptor were expressed on the cell surface region of
Ki67 in combination with the study of miR-22, miR-92a expression and glandular epithelial cells in human endometrium in both the proliferative
methylation of the promoter region of the WIF1 gene can be considered as a (1.75 ± 0.4) and secretory phase (1.1 ± 0.1). The expression of marker
potential diagnostic and prognostic marker for cervical carcinogenesis. was higher in ectopic endometrium of patients with deep infiltrative en-
dometriosis (2.9 ± 0.3) than in the eutopic endometrium in the prolifera-
tive phase of healthy women (p <0.005) and was not significantly differ-
E-PS-09-023 ent from the data of patients with endometrial carcinoma ( 3.1 ± 0.3).
Uterine inflammatory myofibroblastic tumour: report of 2 cases and Conclusion: EphA2 receptor is overexpressed in the ectopic endometri-
literature review um of patients with deep infiltrative endometriosis and in the eutopic
A. Rolim da Paz1, J. Pires de Andrade2, I. De Castro Gomes3, S. Furtado endometrium of patients with endometrial carcinoma. The obtained data
Roberto4, T. Lopes de Medeiros3, E. Moreira de Queiroga2, A. Furtado makes it possible creation targeted therapy for treatment deep infiltrative
Honório Dornelas2,3 endometriosis and cancer.
1
University Hospital Lauro Wanderley/EBSERH/UFPB, Brazil, 2 Cancer
Hospital Napoleão Laureano, Brazil, 3 University Hospital Lauro
Wanderley/EBSERH/UFPB, Brazil, 4 CLIM, Brazil E-PS-09-025
Features of the Vitamin D status and expression of the Vitamin D recep-
Background & Objectives: We reported two patients: the first one, 35 tors in the uterine mucosa in patients with endometrial hyperplasia
years old, previously healthy, sought clinical care in gynaecology to insert E. Kazachkov1, E. Kazachkova1, E. Voropaeva1, A. Zatvornitskaya1
1
an intrauterine device (IUD); during the hysteroscopy examination, there South Ural State Medical University, Russia
Virchows Arch

Background & Objectives: Currently, there is no data on the level of Background & Objectives: Steroid cell ovarian tumours are uncommon
serum 25(OH)D and vitamin D receptors (VDR) expression in the uterine sex cord stromal neoplasms accounting for less than 0,1%. of all ovarian
mucosa in endometrial hyperplasia (EH). The aim is to compare the levels tumours.
of serum 25(OH)D and VDR expression in the uterine mucosa in EH. Methods: We report a case of a 53-year-old postmenopausal female
Methods: We used endometrial biopsy samples obtained from 50 women and complaining of hair loss, deepening of voice and an unusual increase of
divided them into the two following groups: EH and normal uterine mucosa. her libido. Testosterone serum level was elevated. Ultrasonography iden-
We determined the level of serum 25(OH)D using chemiluminescent micro- tified a solid left ovarian mass. Bilateral salpingo-oophorectomy was per-
particle immunoassay (Architect i2000, USA) and VDR expression using formed, leading to complete resolution of symptoms and normalization of
Vitamin D Receptor antibody [C1C2] (Genetex, USA). For a morphometric testosterone level within 1-2 months.
analysis, we used a computerized image analyser Videotest - Morphology 5.2 Results: Macroscopic examination revealed an ovarian yellow solid tu-
(Russia) and applied non-parametric statistical methods. mour replacing almost the whole ovary. Microscopically the diagnosis of
Results: We found the serum 25(OH)D deficiency in 56.67% of patients a steroid cell tumour NOS type with no cytologic atypia was confirmed.
with EH, whereas the serum 25(OH)D level was adequate in 95% of Conclusion: Stromal cell tumours are rare sex hormone secretory neo-
patients with normal uterine mucosa (p = 0.04). plasms, producing symptoms of virilization, particularly hirsutism. They
The differences in the levels of serum 25(OH)D were not significant are divided into three subtypes: stromal luteoma arising from ovarian
between groups (26.76±2.05ng/ml vs. 35.76±3.67ng/ml, respectively) stromal cells, Leydig cell tumour from Leydig cells in the hilum of the
(p = 0.06). In patients with EH, we noted the following types of endome- ovary and steroid cell tumour not otherwise specified (NOS). The last
trial VDR expression: diffuse (10%), focal (23,33%), and single-cell subtype accounts for 60% of all and has malignant clinical behaviour in
(36.67%). The rest 30% of the samples were VDR negative. In patients 25-45%. Histologically the tumour cells arrange in nests, columns or
with normal uterine mucosa, the negative and single-cell expression types cords. They are polygonal-round, with eosinophilic, clear or vacuolated
were absent, whereas the diffuse type prevailed over the focal type (70% cytoplasm, with central nuclei and prominent nucleoli. The absence of
and 30%, respectively). Rienke's crystals differentiate the tumour from Leydig cell neoplasms.
Conclusion: Patients with HE had serum vitamin D deficiency and a Sensitive immunohistochemical markers are inhibin and calretinin and
pronounced decrease in the endometrial VDR level, which possibly en- positive markers are CD99, cytokeratin, S100p. Hayes and Scully iden-
hanced endometrial proliferation. tified five pathological characteristics of malignancy:1) two or more
mitoses/10HPF 2) necrosis 3) hemorrhage 4)tumour diameter>7cm and
5)grade 2 or 3 nuclear atypia. Bilateral salpingo-oophorectomy is a safe
E-PS-09-026 therapy option.
Vaginal recurrence of endometrial carcinoma could be avoided
S. Stolnicu1, C. Terinte2, N. Ioanid3
1
Department of Pathology, UMFST, Targu Mures, Romania, E-PS-09-028
2
Department of Pathology, Oncologic Institute Iasi, Romania, The role of anti-mullerian hormone in pathogenesis of endometriosis
3
Department of Surgery, Oncologic Institute Iasi, Romania E. Kogan1, N. Paramonova1, T. Semeryuk1
1
First Moscow State Medical University (Sechenov University), Russia
Background & Objectives: The risk of vaginal recurrence in endome-
trial cancer ranges from 7% to 13% and has been related to various Background & Objectives: Anti-mullerian hormone (AMH) is a signif-
parameters (age, tumour type and grade, depth and type of myometrial icant regulator of a female reproductive function. The study of AMH
invasion, presence of lympho-vascular invasion). Patients with vaginal expression may help to clarify the pathogenesis of several
recurrence are treated with surgery and radiotherapy. However, little is ggynaecological diseases including endometriosis.
known regarding the mechanism and how to avoid the development of Aim. To evaluate expressions of AMH and AMH receptors 2 (AMHR2)
vaginal recurrences. in patients with deep infiltrative endometriosis.
Methods: A prospective study involved 7 cases of endometrial carcino- Methods: The study was performed on the surgical materials and mate-
ma surgically treated with classic laparotomy. In every case, 2 smears rial of endometrial samples, which were recieved from 36 women diag-
were collected from the proximal vagina around the cervix before surgery nosed with infiltrative endometriosis of rectovaginal septum and vagina
and 2 additional smears during surgery, before cutting the upper part of and from 34 women diagnosed with combined infiltrative endometriosis
the vagina to remove the uterus. All smears were stained with of rectum, rectovaginal septum and vagina. The control group consists of
Papanicolaou and the presence of atypical cells in the smears was 20 women with local peritoneal endometriosis. Expression levels of
corelated with the type of the tumour in every case. AMH and AMHR2 was identified by immunohistochemistry analysis
Results: Seven patients (range 47-72 years) presented endometrial carcinoma of epithelium and stroma cells of heterotopic and eutopic endometrium.
of polypoid type, of 3-8 cm diameter and all infiltrating the endocervix. Six Results: Expression of AMH and AMHR 2 was significantly lower in
cases were of endometrioid type with squamous metaplasia, while 1 case was stromal cells of endometriosis than in stromal cells of eutopic endometri-
of clear cell type. Six cases presented tumour cells in all PAP smears, while 1 um. Decrease in AMH and AMHR2 levels was found in stromal cells of
case was negative before surgery, but positive during surgery. eutopic endometrium as a sign of endometriosis progression.
Conclusion: The data from this study suggest that in most cases the Conclusion: Reduced expression of proapoptotic substances such as
vagina is contaminated before surgery due to bleedings however, addi- AMH and AMHR2 in eutopic endometrium and local endometriosis
tional cases may be contaminated during surgery. We propose a change in creates favorable conditions for spreading and engraftment of
the surgical procedure which would be easier and less costly than apply- heterotopiс endometrium as well as for progression of endometriosis.
ing postsurgical vaginal radiotherapy. This finding may be one of the important links to pathogenesis of endo-
metriosis.

E-PS-09-027
Steroid cell tumour of ovary: a rare case report E-PS-09-029
P. Tziakou1, E. Delliou2, V. Papamichail3, A. Zizi-Sermpetzoglou1 Clear cell carcinoma of the endometrium: evaluation of eight cases
1
Department of Pathology of Tzaneio General Hospital of Piraeus, M. Ozsen1, F. Oz Atalay2, Y. Cakir1
Greece, 2 Laboratory of Pathology - Xanthi, Greece, 3 Laboratory of 1
Erzurum Regional Training and Research Hospital, Turkey, 2 Uludag
Pathology "ISTODOMI" - Piraeus, Greece University Faculty of Medicine, Turkey
 Virchows Arch

Background & Objectives: Clear cell carcinoma (CCC) consti- E-PS-09-031

tutes 2% of endometrial carcinomas. It is an estrogen-independent Primary peritoneal müllerian adenosarcoma: report of a case
histological subtype and included in type II (non-endometrioid) L. Barona García1, E. Iborra Lacal2, M.I. Oviedo Ramírez1, A. Salazar
endometrial carcinoma group. The aim of this study is to present Nicolas1, M.I. Ortuño Moreno1, A. Caballero Illanes1, G. Ruiz García1,
the clinicopathological features of these tumours, which are rela- E. Martínez Barba1
1
tively rare in routine pathology practice but should be considered Servicio de Anatomía Patológica. Hospital Clínico Universitario Virgen
in the differential diagnosis because they have a worse prognosis de la Arrixaca, Spain, 2 Hospital Clínico Universitario Virgen de la
than endometrioid carcinoma. Arrixaca, Spain
Methods: In this study, haematoxylin and eosin stained slides of
CCC cases and electronic archive records were reviewed, diag- Background & Objectives: Mullerian adenosarcoma (AS) is a rare mes-
nosed between 2005-2018 in our department. Cases were evaluat- enchymal and epithelial neoplasm of low malignant potential typically
ed retrospectively considering age and clinicopathological features arising from the uterine corpus in perimenopausal or postmenopausal
such as tumour size, myometrial invasion depth, infiltration pat- women. Extra-genital sites such as the peritoneum are extremely rare
tern, different pattern of differentiation, lymphovascular invasion, and are typically found in younger women.
stromal reaction, necrosis, cervical stromal involvement, metasta- Methods: A 71-year-old woman with abdominal pain, dysuria and pal-
sis, and stage. pable abdominal mass. The computed tomography scan (CT) revealed a
Results: A total of eight cases were diagnosed as CCC in hysterectomy 20 × 15 cm pelvic mass occupying the right upper pelvic region, probably
specimens. The mean age of patients was found to be 61.3 (range: 52-72). of adnexal origin. Two biopsies were performed, diagnosed as borderline
The histopathological evaluation revealed papillary, tubulocystic or solid ovarian serous tumour and mucinous adenofibroma. A laparotomy was
patterned tumours showing polygonal, cuboidal, hobnail, and flat-shaped performed, and a peritoneal mass arising from Douglas peritoneum was
cells, some with eosinophilic granular cytoplasms. In one case, carcinoma found and resected. The uterus and adnexa appeared normal.
was observed in endometrial polyp while no relationship was observed Results: Microscopic examination revealed a biphasic tumour with
with polyps in others. intimally admixed glands and prominent stroma configuring finger-like
Conclusion: CCC is a relatively rare type of endometrial carcinoma. It is projections and imparting a leaf-like (phyllodes-like) architecture. No
important in terms of differential diagnosis of serous carcinoma, secretory sarcomatous overgrowth or heterologous differentiation was found. The
type endometrioid carcinoma or endometrioid carcinoma with clear cell epithelial component was focally stratified, with mild to moderate atypia,
changes, endometrioid carcinoma with glycogen-rich squamous metapla- forming a more complex pattern. Primary extrauterine mullerian
sia areas, reactive atypia with hobnail cell metaplasia, and Arias-Stella adenosarcoma with 30% atypical proliferating serous tumour was
reaction, as well as in terms of treatment and follow-up. diagnosed.
Conclusion: The main prognosis factor of AS is the condition referred as
“sarcomatous overgrowth”, when more than 25% of the tumour is com-
E-PS-09-030 posed of pure high-grade sarcoma. This is associated with aggressive
Association of epithelial neoplasias of the uterine cervix with non- clinical behavior. However, independently of sarcomatous overgrowth,
neoplastic processes extra-uterine AS has a very poor prognosis. Lastly, the diagnosis of
M. Shushval1, N. Kozlov2,3, L. Volkova2,3, A. Shatilova2, A. Akimova2, adenofibroma should be made with caution when we have small samples,
A. Antishina2, A. Kapustina2 since distinguishing adenosarcomas can be a challenge.
1
Baltic Federal University, Russia, 2 Immanuel Kant Baltic Federal
University, Kalinigrad, Russia, 3 Lab. of Immunohistochemistry and
Pathology Diagnostics, Russia E-PS-09-032
Analysis of regional peculiarities of intraepitelial neoplastic processes
Background & Objectives: Investigations of background and precan- of the cervix
cerous processes for epithelial neoplasia of uterine cervix are necessary M. Shushval1, N. Kozlov2,3, L. Volkova2,3
1
for understanding of mechanisms of tumour transformation and progres- Baltic Federal University, Russia, 2 Immanuel Kant Baltic Federal
sion. The study aimed to evaluate association between non-tumour pa- University, Kalinigrad, Russia, 3 Lab. of Immunohistochemistry and
thology and neoplasia of the uterine cervix. Pathology Diagnostics, Russia
Methods: Retrospective analysis of clinico-morphological characteristics
of uterine cervix neoplasia in 205 women (2017-2018 years, surgical Background & Objectives: The frequency, structure, peculiarities of
material) for evaluation of association between non-tumour pathology cervical intraepithelial neoplasia aretaking into consideration for planning
and malignancies. Age of patients: 21 -81 years. of prophylaxis, diagnostics and therapy. The aim of study - to assess the
Results: The main cervical neoplasias were found: 1) CIN III (95/ regional specificity of cervical intraepithelial neoplasia characteristics in
46.3%); 2) carcinoma in situ CIS (37/18 %); 3) invasive squamous cell screening cytology in Guryevsk of Kaliningad Region.
carcinoma of different grade (73/ 35.7%). The prevalence of age groups Methods: The study group - examination of cytological smears of 10 511
of women with cervical neoplasias was found: 1) CIN III - 21-40; 2) CIS women (age 29-69 years) in 2017- 2018in Guryevsk Central Hospital.
– 21-50; 3) invasive carcinoma – 31-60 and more. Anamnesis of women: Results: Among the women of study group following cervical
1) quantity of abortions – CIN III (non/43.2 %), CIS (1-2/51.4%), ISCC pathologywas revealed: intraepithelial neoplasia- 40 cases (0.399%),
(3 and more/ 40%); 2) inflammatory processes with or without associa- squamous cell carcinoma- 2 women of age 44 and 69 years (0.019%).
tion with cervical erosion/ectopy - CIN III (62.1 %), CIS (54 %), ISCC LSIL(23) was the more frequent in comparison to HSIL (total -17, CIN II
(73.9 %); 3) ovarian cysts and uterine leomyomas - CIN III (27. 4 %), CIS and CIN III) without significant differencesin average age of patients ( 40
(35.1 %), ISCC (31.6 %); 4) HIV and hepatitis B or C - CIN III (4.3 %), years).HPV positive results: 1) LSIL (23) - 4 (17.39%); 2) HSIL - 10
CIS (10.8 %), ISCC (2.8 %). (58.82%).2 cases of hyperdiagnostics of HSIL in cytology were
Conclusion: Tendency of association between epithelial neopla- found after histological examination (10, 52%). Inqualitative PCR
sias of the uterine cervix and quantity of abortions and labors, the 14 types of HPV of high oncogenic risk were found: 16, 18, 31,
inflammatory processes, ovarian cysts and uterine leiomyomas in 33, 35, 39, 45, 51, 52 , 56, 58, 59, 66, 68.In some cases in anam-
anamnesis of women with HSIL and invasive squamous cell car- nesis of women with LSIL and HSIL the following ggynaecological
cinoma was revealed, in some cases HIV and hepatitis B/C also pathology was marked:cervicitis, erosions, endometritis, salpingo-
were described. oophoritis, bacterial vaginosis.
Virchows Arch

Conclusion: The regional tendencies in characteristics of cervical mass lesion (4,3x2,5x1,5 cm) invading the anterior wall of the uterus
intraepithelial neoplasia are described, improvement of cytological body. PET-CT did not detect the presence of metastasis. Laboratory test
screening and description of ggynaecological pathologyin anamnesis showed a slightly high level of b-HCG.
are necessary forcorrect statistic evaluation and diagnosis and understand- Results: Therapeutic curettage was done and microscopical examination
ing of possible mechanisms of progression of cervical neoplasia. of the endometrial curettage specimen revealed a proliferation of inter-
mediate trophoblasts that showed mild nuclear atypia, low mitotic figures
(2/10 HPF) and Ki67 proliferation index 6%. These cells were positive
E-PS-09-033 for inhibin-A. In addition, some multinucleated cells are present.
Carcinosarcoma of the vagina: HPV typing in two malignant Chorionic villi and cytotrophoblasts were not identified. So, the diagnosis
components of Placental Site Trophoblastic Tumour was elected. Total hysterectomy
D. Doutel1, M. Baiao2, D. Rosa1, C. Cardoso1, G. Fernandez1, J. was performed and microscopical examination from the mass was similar
Caldeira1, D. Cochicho1, A. Felix3 to that described in the curettage specimen with infiltration of 75% of the
1
Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Portugal, myometrium.
2
Nova Medical School - UNL, Portugal, 3 Instituto Portugues de Conclusion: Recognition of these very rare cases might help surgeons to
Oncologia de Lisboa, Nova Medical School - UNL, Portugal predict the behaviour of the tumour and to determine the specific thera-
peutic approach for this patient.
Background & Objectives: Carcinosarcomas of the vagina are extreme-
ly rare neoplasms, with 15 cases reported, 4 of which with squamous-cell
carcinoma (SCC) as the epithelial component and leiomyosarcoma as the E-PS-09-035
sarcomatous component. The study of HPV DNA in both components Case report of a Krukenberg tumour during pregnancy
has been used to evaluate a common clonal origin. Multiple HPV types in G. Panselinas1, I. Efstratiou1, S. Pervana1, E. Pazarli1, O. Batsi1, E.
vaginal SCC are frequently found (11%). Massa1
1
Our aim was to use HPV typing as a tool to identify the same cell of origin General Hospital Papageorgiou, Greece
of both components.
Methods: A 72-year-old woman with vaginal bleeding, submitted to a Background & Objectives: Report of a rare case of Krukenberg tumour
hysterectomy with bilateral adnexectomy for “leiomyomas” 30 years be- presenting with virilization during pregnancy
fore. Vaginal examination found an exophytic tumour with 6 cm. MRI Methods: A 39-year-old woman presented with bilateral adnexal masses,
distinguished two components: an outer component that showed restric- elevated CA-125, ascites and androgenic manifestations during pregnan-
tion in diffusion weighted imaging and also contrast enhancement; and a cy. The differential diagnosis included Krukenberg tumour, a sex cord
inner component with signal characteristics of higher cellularity. stromal tumour of the ovary and a pregnancy luteoma. Gastric biopsies
Vaginal cytology identified High-Grade Squamous Intraepithelial Lesion did not show any evidence of malignancy. The pregnancy was interrupted
and HPV70. A local wide excision was performed and adjuvant chemo at 21st week and surgery was performed. Frozen sections from the ovarian
and radiotherapy used. She is alive without evidence of disease ten tumours showed diffuse infiltration of both ovaries by signet ring cells
months after. arranged individually or in clusters.
Results: The histopathological study revealed a biphasic neoplasm with Results: An intraoperative diagnosis of Κrukenberg tumour was made and
two components: an invasive SCC (predominantly in-situ) and a the patient underwent bilateral salpingoophorectomy which confirmed the
leiomyosarcoma. Both components were isolated from the paraffin diagnosis by the consequent routine histologic and immunohistochemical
blocks and the HPV typing was done using INNOLipa® separately, studies . Gastroscopy following the surgery revealed a signet ring cell adeno-
which showed HPV70 and HPV16 in the epithelial and mesenchymal carcinoma. The patient was treated with chemotherapy but the tumour re-
component, respectively. lapsed and the patient died one year after the surgery.
Conclusion: The presence of two different HPV types is puzzeling and it Conclusion: Krukenberg tumour can present with androgenic manifesta-
has not been described before in vagina carcinosarcomas, but allows to tions and mimic a sex cord stromal tumour or a pregnancy luteoma of the
infer that the sarcomatous component is derived from an epithelial cell as ovary. The primary carcinoma is an often occult gastric cancer in about
HPV16 strictly infects epithelial cells. 2/3 of the cases.

E-PS-09-034 E-PS-09-036
Placental site trophoblastic Tumour: a case report The endometrial expression of LIF and LIFR in infertile patients
D. Anestakis1, C. Tsompanidou2, M.I. Givannakis3, E. Chatzifotiou1, E. with adenomyosis, myoma, uterine malformations, synechia and
Kalyva4, C. Charalampidis5 polyps during the window of implantation
1
Department of Autopsy Histopathology, Lab. of Forensic Medicine and A. Asaturova1, I. Kozachenko2, N. Fayzullina2, A. Shchegolev2, L.
Toxicology, Aristotle University of Thessaloniki, Greece, 2 Department Adamyan2
1
of Pathology, General Hospital of Thessaloniki "Agios Dimitrios" , FSBI 'National Center for Obstetrics, Gynaecology and Perinatology
Greece, 3 Surgical Department , General Hospital "AHEPA", named after V.I.Kulakov' Ministry of Healthcare Russian Federation,
Thessaloniki Greece, 4 Thessaloniki Forensic Service, Thessaloniki, Russia, 2 FSBI "National Center for Obstetrics, Gynaecology and
Greece, 5 Department of Anatomy, Democritus University of Thrace, Perinatology named after V.I. Kulakov" Ministry of Healthcare, Russia
Greece
Background & Objectives: Adenomyosis, myoma, uterine
Background & Objectives: Placental Site Trophoblastic Tumour is a malformations, synechia, polyps were found to have negative im-
rare variant of gestational trophoblastic disease that occur mainly in wom- pact on embryo implantation. Leukemia inhibitory factor (LIF), is a
en who have history of miscarriage, termination of pregnancy or even a molecular marker for endometrial receptivity, has an effect through
normal or pathological ongoing pregnancy. The clinical course is the LIF receptor (LIFR) on both the embryo and the endometrium
unpredictable. site. The aim of our study was to evaluate the endometrial expres-
Methods: A 32-year-old woman eleven months following a prior full sion of LIF and LIFR in patients with adenomyosis, myoma, uterine
term normal pregnancy presented to the hospital with a history of two malformations, synechia and polyps during the window of implan-
months of amenorrhea. Ultrasonography and MRI showed an ill-defined tation (WOI).
 Virchows Arch

Methods: Endometrium was obtained during the WOI from infertile Background & Objectives: Chronic pelvic pain (CPP) causes neurolog-
patients of reproductive age planning IVF with adenomyosis (10 pa- ical changes in the dorsal horn of the spine, resulting in neurogenic in-
tients), myoma (10 patients), uterine malformations (10 patients), flammation of multiple pelvic viscera, hyperalgesia, dysreflexia, a lower
synechia (10 patients) and polyps (10 patients) before and after surgery. sensory threshold and, therefore, a greater perception of pain.
In the comparative group were 10 patients with tubal factor of infertility Endometriosis is observed in 71 to 87 percent of women with chronic
and without any uterine pathology. The LIF and LIFR expressions were pelvic pain.
measured by immunohistochemistry for protein intensity and The aim of the study was to investigate neurotrophins and nerve associ-
localization. ated peptides in endometriotic lesions of different localization from pa-
Results: The mean age of the patients was as follows: tients with CPP.
adenomyosis (35,9±0,5 years), myoma (36,2±5,2), uterine Methods: For all patients the intensity of the pain symptoms was
malformations (29,0±5,1), synechia (34,2±0,7) and polyps (32, 8 registered using a Visual Analogue Scale. For IHC staining were
±1,7). Patients with adenomyosis, myoma, uterine malformations, used antibodies to NGF, VIP, tyrosine hydroxylase, peripherin and
synechia and polyps showed significantly and parallel reduced synaptophysin were used. For study of spatial relationship of
LIF and LIFR expressions in the eutopic endometrium during nerve fibers 3D reconstruction of confocal images of some cases
WOI as compared with the control group. An increase in the level were used.
of expression of LIF and LIFR was observed after surgery, which Results: All endometriotic lesions was classified corresponding to
correlated with positive results of IVF. their immunohistochemical profile. We found correlation between
Conclusion: Significant reduction of LIF and LIFR expression as expression of neurotrophins and nerve associated peptides and
markers of endometrial receptivity explains the negative impact of severity of CPP.
adenomyosis, myoma, uterine malformations, synechia and polyps on Conclusion: New information about neoneurogenesis and growth direc-
implantation processes and hence the results of IVF. tion of sensitive nerve terminal were onatained.

E-PS-09-037 E-PS-09-039
Pathology of placental circulation in prolonged pregnance Evolution of white conisations at the pathological anatomy's service
A. Drobintseva1, V. Polyakova1, S. Makarenko2, J. Krylova2,3 of the University Clinical Hospital Virgen de la Arrixaca
1
D.O. Ott. Research Institute of Obstetrics, Gynaecology and A. Salazar Nicolas1, M.I. Ortuño Moreno1, L. Barona Garcia1, A.
Reproductology., Russia, 2 Saint-Petersburg Medico-Social Caballero Illanes1, M.D. Perez Caparros2, N. Villa Lorente3, M.A.
Institute, Russia, 3 Pavlov First Saint Petersburg State Medical Menárguez Arnaldos4, G. Ruiz Garcia1, M.I. Oviedo Ramirez5, M.A.
University, Russia Torroba Carón1, E. Martinez Barba1
1
Servicio de Anatomía Patológica, Hospital Clínico Universitario Virgen
Background & Objectives: The reported frequency of postterm preg- de la Arrixaca, Spain, 2 Servicio de Ginecología y Obstetricia, Hospital de
nancy is approximately 3-17% . Recent studies shown that postterm de- Mèrida, Spain, 3 Servicio de Anestesia y Reanimación, Hospital Clínico
livery is at risk of complications such as hypoxia, birth injury and even Universitario Virgen de la Arrixaca, Spain, 4 Servicio de Urgencias,
stillbirth. As the placenta ages, increased rates of placental infarction and Hospital Clínico Universitario Virgen de la Arrixaca, Spain, 5 Servicio
fibrin deposition. de Anatomía Patológica. Hospital Clínico Universitario Virgen de la
The aim of the study was to examine the circulation system in placental Arrixaca, Spain
tissue in prolonged pregnancy.
Methods: The object of the study was placenta, the investigated Background & Objectives: In many occasions, we can find
groups were 41 g.w. (n=20), >42 g.w. (n=20) and 38-40 g.w. conization pieces that come to us due to high-grade lesions in
(n=20). Analysis of morphofunctional state were performed by previous biopsies but, once the histological study in done, there
using clinical data and morphological findings. Primary monoclo- is no trace of those leions described previouysly. These conizations
nal antibodies to KISS1 (1:100, Abcam), KISS1R (1:350, are calld white conizations. Many studies show that, despite being
Abcam), CD34 (1:100, Dako) and eNOS (1:150, Abcam) were histologically confirmed in a previous CIN2-3 biopsy, in approxi-
used for IHC method. Alexa Fluor 488 and 647 (1:1000, mately 10-20% of the conizations there is absence of CIN 2-3
Abcam) were taken as secondary antibodies. 3D reconstruction lesion.
of vessels, analysis of diameter of capillars and comparsion of Methods: Conizations are analysed in the period of time from 2013 to
eNOS expression were made. 2017 (664 total conizations, 521 diagnostic conizations and 141 white
Results: The number of placenta infarction and acute circulation conizations), studying the proportion of conizations considered as white
injury increase sharply after 41 weeks of gestation. The average before and after incorporating processing and histological improvements
area of eNOS expression in placental villi was 2 times lower in in the study of the samples, comparing the incidence of white conizations
group with 42 weeks gestational age compare to control group. with respect to the data reflected in the last series published in the bibli-
Expression of KISS1 and KISS1R was elevated compare to con- ography found.
trol group. The improvements include the gynaecology and obstetrics service by
Conclusion: We assume that circulation injury established in placenta of sending the fresh sample instead of coagulating the piece. In the
prolonged pregnancy could lead to severe hypoxia and other fetal and Pathological Anatomy’s service, the remitted piece is spread over a piece
neonatal risks. of cork and held it with sterile needles to maintain the anatomical position
and a systematics of carving by time slots. Regarding the histological
study, the LAST terminology and the complementary study with the
E-PS-09-038 P16 technique were implanted.
Expression of signal molecules associated with generation of chronic Results: From 2013 to 2014, 248 conizations were made, of
pelvic pain in patients with endometriosis which, 75 were white (30.2% of the total). That was very far away
A. Drobintseva1, J. Krylova1,2, A. Andreev1, V. Polyakova1, I. Kvetnoy1 from what was published in last publications. Once improvements
1
D.O. Ott. Research Institute of Obstetrics, Gynaecology and were established in the obtaining, processing and study of the
Reproductology, Russia, 2 Pavlov First Saint Petersburg State Medical conizations since 2015, 416 conizations were made between
University, Russia 2015-2017, of which 66 white ones assuming 15.9% of the total,
Virchows Arch

being an acceptable percentage. If we look at the data per year, to gynaecology clinic. Ggynaecological ultrasound and abdominal com-
we see how the percentage decreases referred to white puted tomography revealed enlargement of uterus with a heterogeneous
conizations: 2015 with 133 conizations and 28 white conizations endometrium and myometrium corresponding a malignancy. Left adnexa
(21%), 2016 136 conizations and 21 white conizations (15.4%) was also seen solid and enlarged. The uterus and the both adnexa were
and 2017 were made 147 conizations being 17 considered as adherent to surrounding soft tissues. The wall of the urinary bladder and
white ones (11.4%). sigmoid colon were thickened asymmetrically. Also there were many
Conclusion: enlarged lymph nodes in pelvic, mesenteric and paraaortic regions.
- Achieving the conizations without electrocoagulation and sending the Uterus and both adnexa were resected for frozen section examination.
sample in fresh to the Pathological Anatomy service decreases the ar- However, it could not allow an exact diagnosis excluding malignancy.
chitectural distortion. At operation it was revealed that uterus, both adnexa, bladder, sigmoid
- A systematic setting and carving improves the study of the piece. colon, rectum, omentum were adherent to each other. Samples taken from
- Unification of the terminology used and usage of P16 technique guar- these organs and lymph nodes were histopathologically examined.
antees a lower incidence of white conizations. Results: Microscopically the whole uterus, ovaries, tuba uterinas and the
samples taken from bladder, sigmoid colon and rectum showed dense
Supported by Servicio Murciano de Salud de la Región de Murcia. foamy histiocytic infiltration, granuloma formations with dispersed lym-
phocytes, plasmocytes and neutrophils with Michaelis-Gutman bodies
diagnosing Malakoplakia.
E-PS-09-040 Conclusion: Whilst the etiology of malakoplakia is uncertain it is be-
Ovarian teratomas with somatic malignant transformation: report of lieved to be associated with defective macrophage phagocytic function
two cases causing overgrowth of microorganisms because of inability of destroying
A.P. Rodrigues1, J. Pardal1 of digested bacteria. Coliform bacteria have been the most common as-
1
Hospital de Braga, Portugal sociated microorganism. The treatment includes antibiotics and surgical
excision in extensive malakoplakia.
Background & Objectives: Malignant transformation is a rare phenom-
enon in ovarian teratomas. Mature cystic teratoma is the most common
ovarian neoplasm. Nevertheless, malignancy is described in 1‐2% of E-PS-09-042
cases. Struma ovarii is a monodermal teratoma representing 2-5% of all Fibroepithelial stromal polyp of labium minus
ovarian teratomas. The presence of thyroid cancer in struma ovarii is even O. Ilhan Celik1, S.Y. Celik1, Y. Dere1
1
rarer, occurring in 0.5-5% of cases. We report two cases of somatic ma- Mugla Sitki Kocman University, Faculty of Medicine, Department of
lignant neoplasm in teratomas. Pathology, Turkey
Methods: Case 1– A 45-year-old woman presented with abdominal pain.
Ultrasonography and magnetic resonance scanning revealed an abdomi- Background & Objectives: Fibroepithelial stromal polyp(FSP) is a be-
nal mass with 11x10x8 cm in the left uterine appendage. nign mesenchymal lesion typically seen in women of reproductive age. It
Case 2- A 45-year-old woman presented with a left‐sided pelvic mass on is generally site-specific and presents commonly in vulvovaginal region.
physical examination. Ultrasonography confirmed the findings, revealing Methods: A 38-year-old woman suffering from a mass on her labium minus
a 13.4x8.7 cm mass in the left uterine appendage. was referred to gynaecology clinic. It had first been noticed 3 months earlier as a
Both patients underwent surgery. small nodule; however it had grown rapidly during the past 2 months. Physical
Results: Microscopic examination showed somatic‐type malignant le- examination revealed a soft, polypoid, painless mass with a diameter of 7cm on
sions associated with teratomas. her right labium minus. Total surgical resection of the lesion was performed.
Case 1- A nodular area with prominent papillae was identified within Results: In the histopathological examination, the lesion was composed
struma ovarii. Histological features of papillary thyroid carcinoma were of bland mesenchymal stellate, spindle shaped cells and multinucleated
observed. giant cells in a myxoid, loose fibrous stroma. No nuclear atypia or in-
Case 2- A trilineage mature cystic teratoma with a component of invasive creased mitotic activity was seen. Immunohistochemical studies revealed
squamous cell carcinoma was observed. The latter corresponded to a that the cells of the lesion were positively stained with Vimentin, Desmin,
polypoid solid lesion on gross examination. Estrogene and progesterone receptors. The lesion was diagnosed as FSP.
Image and biochemical surveillance was the established post‐surgery ap- No recurrence was seen in 4 months after the resection.
proach for both patients. Both patients are alive with no evidence of Conclusion: FSP (formerly known as pseudosarcoma botryoides) is a
disease. benign mesenchymal lesion that typically occur in the vulvovaginal re-
Conclusion: We describe two cases of unusual malignancies that can gion of women in reproductive age. It generally presents as a polypoid or
occur in daily practice. A postmenopausal setting, older age, large tumour pedunculated mass, usually measuring less than 5cm in diameter. It rarely
masses and the presence of solid areas in gross examination are important causes local symptoms such as bleeding or discomfort and is known to be
clues that should raise the possibility of malignant transformation. associated with hormonal exposure like pregnancy or usage of hormone
replacement therapy. Total excision is the treatment. It rarely recurs and
no lymph-node or distant organ metastasis have been reported.
E-PS-09-041
Widespread malakoplakia of urogenital and gastrointestinal systems
O. Ilhan Celik1, S.Y. Celik1, L. Tekin1, Y. Dere1 E-PS-09-043
1
Mugla Sitki Kocman University, Faculty of Medicine, Department of Ovarian gastric type mucinous carcinoma arising in incidentally
Pathology, Turkey found mature cystic teratoma: a case report
K.E. Kaçar1, I.E. Seven1, F. Eren1
1
Background & Objectives: Malakoplakia is a rare, chronic, Marmara University, Turkey
xanthogranulomatous inflamatory disease usually encountered in urinary
and gastrointestinal systems of middle-aged women. It rarely affects fe- Background & Objectives: Mucinous carcinoma accounts for %3-4 of
male genital tract. all primary ovarian carcinomas. Approximately %5 of mucinous tumours
Methods: A 57-year-old woman suffering from lower abdominal dis- arise in mature cystic teratomas and most of them are benign whereas
comfort, intermittent vaginal bleeding in the last 6 months was referred carcinoma is rare.
 Virchows Arch

Methods: A 26-year-old woman presented with abdominal distention Background & Objectives: Low grade serous carcinoma (LGSC) is a rare
and abdominal pain. A giant 26x22x12cm abdominopelvic mass extend- tumour of the ovary. Most ovarian serous carcinomas are high grade tu-
ing from symphisis pubis to the sternum was palpated. MR imaging mours, whereas LGSC accounts for < %10 of all ovarian serous carcinomas.
revealed a cystic dominant mass with solid component. The patient Methods: A 51-year-old woman with no medical/surgical history pre-
underwent an exploratory laparotomy. A large ovarian cyst was sent for sented with lower abdominal pain. She underwent exploratory laparoto-
intraoperative consultation, it was evaluated as borderline mucinous tu- my for optimal debulking, including total abdominal hysterectomy, bilat-
mour. The tumour was sampled by one section per centimeter. The mi- eral salpingo-oophorectomy, total omentectomy, and appendectomy.
croscopy revealed mostly borderline mucinous tumour with focal areas of Results: On gross examination, the uterus, omentum, and appendix were
mucinous carcinoma with expansile type invasion. The mucinous epithe- unremarkable. Grossly, the left ovary measured 17×15×7.5cm with rup-
lium was composed of gastric pyloric type epithelium which was CK 7 tured capsule, and the cut surface was solid and gray with focally hemor-
and Muc6 positive and CK20 negative. In addition to mucinous tumour rhagic areas. On microscopic examination, the tumour consisted of elon-
one section revealed a teratoma component composed of mature ectoder- gated aggregates of cribriform glands. Intraluminal and intracytoplasmic
mal elements. Although additional sampes were taken we could not find mucin was detected. Tumour cells had moderate nuclear atypia. Mitotic
any more teratoma foci. index was lower than 12/10 HPF. The immunoprofile of this tumour
Results: With these features the tumour is diagnosed as a gastric type showed negative staining for CK20, CDX2, CEA and diffuse strong pos-
mucinous carcinoma arising in mature cystic teratoma. itive staining for estrogen receptor, CK7, PAX8, CA125. Staining for WT1,
Conclusion: The origin of primary ovarian mucinous carcinomas is not vimentin, progesterone receptor was patchy with strong intensity and stain-
very well documented. Although association of teratoma and mucinous ing for p53 was wild type. We diagnosed as “cribriform pattern of low-
tumours are well known, this association could be reported in limited grade serous carcinoma with mucinous differantiation”.
cases. The reason for this could be that the teratoma component may be Conclusion: Silva et al. reported 40 cases with LGSC. Mucin was detected
very focal as in our case, so increasing sample size can be helpful in either in intracytoplasmic or between the groups of tumour cells, in 31
determining the origin. cases. The differential diagnosis includes endometroid carcinoma with mu-
cinous differentiation, mucinous carcinoma and seromucinous carcinoma.
The morphological findings and immunohistochemistry results supported a
E-PS-09-044 diagnosis of cribriform pattern of LGSC with mucinous differantiation.
Squamous cell carcinoma of the uterine cervix associated with sys-
temic sarcoidosis
O. Ilhan Celik1, S.Y. Celik1, Y. Dere1, L. Tekin1 E-PS-09-046
1
Mugla Sitki Kocman University, Faculty of Medicine, Department of Uterine leiomyosarcoma and retroperitoneal paraganglioma: spo-
Pathology, Turkey radic association or genetic syndrome?
B. Simona1, A.C. Lisievici2, T.A. Georgescu3, F. Pop4
1
Background & Objectives: Squamous Cell Carcinoma of the Uterine Spitalul Universitar de Urgenta Bucuresti (SUUB), Romania, 2 Carol
Cervix (SCC-C) is one of the most common ggynaecological cancers of Davila University of Medicine and Pharmacy, Bucharest, Romania,
3
women. Sarcoidosis is a systemic disease of unknown etiology Department of Pathology, Bucharest Emergency University Hospital,
characterised by the presence of noncaseating-granulomas in any organ, Romania, 4 "Dr. Carol Davila" University Hospital of Nephrology,
most commonly the lungs and intrathoracic lymph-nodes. The synchro- Romania
nous of sarcoidosis and a solid tumour is a rare condition.
Methods: A 56-year-old postmenopausal woman complaining from swell- Background & Objectives: Paragangliomas are rare neuroendocrine
ing on her neck, vaginal bleeding, spontaneous weight loss of 20kilograms neoplasms arising from paraganglia, which can be sympathetic or para-
in 4 months was referred to gynaecology clinic. Pelvic examination re- sympathetic. In the adrenal medulla they are called pheochromocytoma,
vealed a haemorrhagic-lesion in her cervix and the histopathologic exami- but they can also occur in the head and neck, retroperitoneum and bladder.
nation of the incisional biopsy of it exposed moderate-differentiated-SCC- Paragangliomas can be sporadic, or can appear in a variety of familial
C. The computed tomography revealed a localized lesion in her cervix uteri syndromes: von Hippel Lindau, MEN 2A and 2B, Carney-Stratakis syn-
corresponding a malignancy and many enlarged lymph nodes in pelvic, drome or associated with SDH mutation. Nonetheless, to our knowledge,
abdominale, hilar regions of lungs, also solid nodules in lungs and the liver. there are no reports of the association between extra-adrenal
Results: Submandibular(3cm) and hilar(5cm) lymph nodes were surgi- paraganglioma and uterine leyomiosarcoma.
cally excised and histopathologically diagnosed as Sarcoidosis. After the Methods: We report the case of a 65-year-old female, who first presented
radical-hysterectomy, bilateral-salpingo-oophorectomy, pelvic lymphad- to our clinic in September 2018 and underwent surgery for uterine
enectomy, it was seen that the tumour was localized to the cervix uteri and leiomyosarcoma. In March 2019, a postoperative control CT scan revealed
no metastasis was present in the lymph-nodes; however, all of the pelvic a retroperitoneal mass in direct contact with the transverse colon and the
lymph-nodes excised were diagnosed as sarcoidosis. She was treated with lesser curvature of the stomach. The tumour had a diameter of 15 cm, but
additional external whole-pelvis irradiation for SCC-C and slight did not encompass large abdominal vessels. The patient underwent surgery
immunsupression for sarcoidosis. Her lymph-nodes, lung and liver nod- and the resected specimen was sent to the Department of Pathology.
ules regressed and SCC-C hasn’t recurred in the following year. Results: Histopathological examination revealed a trabecular and nested
Conclusion: It’s important to differentiate this rare coexistence from the proliferation of cells separated by fibrovascular septae, featuring finely
localized sarcoid reactions in regional-lymph-nodes of solid granular cytoplasm and stippled nuclear chromatin. We identified areas of
tumours(LSR-LN-ST). Because Multisystem Sarcoidosis may need to hemorrhage and comedonecrosis, but no invasion of lymphovascular
be treated; however, LSR-LN-ST regress spontanously and don’t require spaces, gastric or bowel wall. The tumour revealed a Ki-67 proliferative
treatment. index of 7% and diffuse reactivity for Chromogranin and NSE. The
surrounding sustentacular cells were positive for S-100. SDHA and
SDHB were not evaluated due to the lack of these markers in our lab.
E-PS-09-045 Conclusion: Coexistence of paraganglioma with other tumours is usually
Low grade serous carcinoma with extensive mucinous differentiation described in rare syndromes, such as Carney triad, a non-hereditary condi-
mimicking seromucinous carcinoma of the ovary tion which also encompasses gastrointestinal stromal tumour and pulmo-
G. Kir1, T. Soylemez1, A. Aydin1 nary chondroma. Similar associations with other tumours have also been
1
Istanbul Medeniyet University, Department of Pathology, Turkey described. To our knowledge, this is the first case report of extra-adrenal
Virchows Arch

paraganglioma associated with uterine leiomyosarcoma and we believe that E-PS-09-049

this occurrence may not be fortuitous and worthy of further investigation. Utility of p16, ER, Vimentin and CEA expression in differential di-
agnosis between endocervical and endometrial adenocarcinoma
J.H. Nam1, N.I. KIM1, Y. CHOI1
1
E-PS-09-047 Chonnam National University Hospital, Republic of Korea
A rare entity; ovarian lipoma
S.Y. Celik1, O. Ilhan Celik1, Y. Dere1, L. Tekin1 Background & Objectives: When clinical and histopathological exami-
1
Mugla Sitki Kocman University, Faculty of Medicine, Department of nation is not effective in determining the primary endocervical adenocarci-
Pathology, Turkey noma (ECAs) and endometrial adenocarcinoma (EMAs), immunohisto-
chemistry (IHC) for ER, Vimentin (Vm), CEA and p16 is regularly used
Background & Objectives: Ovarian Lipoma is a very rare lesion. Most of in practice. The aim of this study was to evaluate the performance of these 4
the lipomatous lesions of ovary are reported as a part of teratoma. However, IHC markers in differential diagnosis between ECAs and EMAs.
this case was not associated with a teratoma or any other lesions. Methods: IHC for p16, ER, Vimentin (Vm) and CEA was performed on
Methods: While a 31-year-old woman was in follow up for pregnancy, an 17 ECAs and 34 EMAs (including 31 EMAs, 2 serous and 1 clear cell
exophytic, nodular, 2 cm lesion in the left ovary was identified by ultrasound carcinomas).
examination. The other parts of the ovary seemed normal. During the opera- Results: Positivity rates of p16, ER, Vm and CEA in ECAs were 94.1%,
tion of cesarean this lesion was totally excised preserving the rest of the ovary. 23.5%, 5.9% and 76.5%, respectively; those in EMAs were 16.1%, 67.7%,
Results: In the histopathological examination the lesion was completely 71.0%, and 38.7%, respectively; those in serous and clear cell carcinomas
composed of benign, mature, monomorphic lipocytes constituting solid were 100%, 0%, 66.7% and 33.3%, respectively. All endocervical adeno-
sheets. The lesion was encapsulated in the parenchym of the ovary. It did carcinomas except for one case demonstrated diffuse and moderate to
not include any other tissues of different origin. So the lesion was diag- strong p16 expression. In contrast, grade 1 endometrioid adenocarcinomas
nosed as Ovarian lipoma. No recurrence or lymph node, distant organ exhibited less diffuse and less intense expression with variable staining
metastasis were seen in 6 months after the resection. intensity. Similar to endocervical adenocarcinomas, all serous and clear cell
Conclusion: Lipoma is the most common benign tumour of the soft tis- carcinomas showed diffuse and moderate to strong p16 expression. The
sues. It is composed of benign, mature, uniform lipocytes and has a thin sensitivity and negative predictive value (96.3% and 94.1%) of p16 expres-
fibrous capsule seperating it from the surrounding tissues. However, lipoma sion and the specificity and positive predictive value (95.7%, and 94.1%) of
of the ovary is a very rare entity. Lipomatous lesions are generally defined Vm expression in differential diagnosis between ECAs and EMAs were
as associated with teratomas, lipid cell tumours and lipoleiomyomas. As it significantly higher than those of ER and CEA expression.
is a benign tumour total excision is the treatment. It rarely recurs and no Conclusion: p16 and Vm are more useful IHC markers and two-marker
lymph node or distant organ metastasis have been reported. So it is impor- panel is recommended for using in differential diagnosis between ECAs
tant to recognise it in order to protect the rest of the ovary from excision. and EMAs.

E-PS-09-048 E-PS-09-050
Persistent vaginal melanoma as an unusual mimic in the endocervix Morphological substrat and pathogenetic mechanisms of adhesion-
I. Busmanis1, D. Seow1 related pelvic in endometriosis
1
Singapore General Hospital, Singapore J. Krylova1,2, S. Kruglov2, V. Bezhenar2, M. Rybakova2
1
D.O. Ott. Research Institute of Obstetrics, Gynaecology and
Background & Objectives: Primary vaginal melanoma of the cervix is Reproductology, Russia, 2 Pavlov First Saint Petersburg State Medical
exceedingly rare, accounting for <3% of vaginal malignancies and <0.3% University, Russia
of all melanomas.
Methods: Case Report Background & Objectives: Endometriosis is one of the most common
Results: A 61-year-old Chinese female initially presented with a 3cm ggynaecological pathologies with complex pathogenesis and a variety of
vaginal polyp, diagnosed as melanoma, and found to harbour a c-kit muta- clinical manifestations. It is prone to high frequency of relapses and
tion. Two years later she presented with recurrent disease manifest as vag- development of adhesions. The aim of the study was to determine the
inal and vulval melanoma-in-situ, synchronously with gastric bleeding from potential of the peritoneum in infiltrative forms of endometriosis with
a biopsy proven 7cm gastric metastasis of melanoma. Ten months later development of adhesions.
further vaginal bleeding necessitated a THBSO and partial vaginectomy/ Methods: The material for the study included peritoneal samples obtain-
vulvectomy. Examination revealed multiple nodular metastases within the ed from women with infiltrative endometriosis and without endometri-
vaginal wall, up to 1.4cm, associated with vascular emboli, and separate osis. Microscopic examination was conducted using the colors: hematox-
foci of primary vulval melanoma-in-situ, lentiginous type. A unique feature ylin and eosin, Van Gieson's stain, PAS. For IHC (1: 150, Abcam), VIP
in the cervix was colonisation within intact endocervical glands by highly (1: 150, Abcam), tyrosine hydroxylase (1: 350, Abcam), Substance P (1:
pleomorphic melanoma cells, situated near to small stromal metastatic de- 350, Abcam), CD117 (1: 350 , Abcam), TGF beta 1 (1: 350, Abcam).
posits. Six months later inexorable disease resulted in eventual death. Results: Microscopic examination was dominated by active foci, repre-
Conclusion: Histologically, the most common subtype of primary vagi- sented by cytogenic stroma and proliferative type glands. Endometrioid
nal melanoma is nodular subtype, followed by mucosal lentiginous. If the lesions had perivascular growth and pronounced neovasculogenesis, as
tumour is amelanotic, awareness of the possibility must be maintained in well as perineural growth and inflammatory infiltration from moderate to
order to apply appropriate immunostains, and not misdiagnose a poorly severe. The immunohistochemical profile of heterotopias corresponded to
differentiated tumour as squamous, or adenocarcinoma, small cell carci- the profile of the intact peritoneum and demonstrated high levels of
noma, or leiomyosarcoma. The unique feature of this case is the first neutrophins, proliferative activity of telocytes and fibrotic markers.
known situation of melanoma potentially mimicking endocervical Conclusion: Improving understanding of the pathogenesis of endometri-
adenocarcinoma-in-situ on solely histologic grounds, but in the back- osis will contribute to the search for therapeutic goals that can provide the
ground of recurrent multifocal metastatic, and primary disease. necessary ways to treat endometriosis.
 Virchows Arch

E-PS-09-051 Results: The cytology of the fluid showed evidence of metastatic disease
Angiosarcoma arising in recurred mature cystic teratoma of the whereas the imprint presented a poorly differentiated ovarian malignant neo-
ovary plasm. The histopathology report revealed a SCCOPT arising in a 31,4 cm
J.H. Nam1, N.I. KIM1, Y. CHOI1 MCT of the left ovary. A small synchronous cystic teratoma was also found
1
Chonnam National University Hospital, Republic of Korea within the right ovary. Immunohistochemically tumour cells expressed:
pankeratin, EMA and CD56. NSE and chromograninA were also focally pos-
Background & Objectives: While the most of mature cystic teratoma is itive. Synaptophysin, MelanA, calretinin, vimentin, p53, Ca125, CK7, CK20
benign, it may rarely undergo malignant transformation. Malignant transforma- and ER were negative. Ki67(MIB1) index of cell proliferation was ~ 70%.
tion in this type of neoplasm is mostly represented by squamous cell carcinoma Conclusion: Malignant transformation of a cystic teratoma is a rare find-
and sarcomas very rarely develop in mature cystic teratoma. To our knowledge, ing (1,8%). SCCOPT is an extremely rare form of ovarian cancer.
this is the ninth case of angiosarcoma arising in mature cystic teratoma. Histopathology, Cytopathology as well some specific tumour markers
Methods: Herein, we also describe the clinicopathologic features of this may be useful in diagnosing correctly an unexpected ovarian malignancy.
unique case and the literature is reviewed.
Results: The patient was an 18-year-old female with 1 week duration of
repeated abdominal pain and tenderness. Her past medical history included E-PS-09-053
previous bilateral cystectomy and was diagnosed with mature cystic terato- Cross-talk between epithelial-mesenchymal transition, angiogenesis
ma of both ovaries 8 years ago. On physical examination, the patient had a and natural killers in borderline ovarian tumours complicating
palpable abdominal mass and was further evaluated with pelvis magnetic pregnancy
resonance images. The examination showed 25cm sized huge cystic mass in A. Asaturova1, M. Shamarakova2
1
left ovary and 8cm sized cystic mass in right ovary. Emergency operation FSBI 'National Center for Obstetrics, Gynaecology and Perinatology
was performed due to left ovarian torsion. Macroscopically the left ovarian named after V.I.Kulakov' Ministry of Healthcare Russian Federation,
tumour consisted of red to brownish cystic mass with extensive hemorrhage Russia, 2 Family Planning and Reproduction Center (Moscow), Russia
and necrotic surface. The tumour measured 20.0 cm in greatest dimension.
The right ovarian mass was 7.5 cm at its greatest dimension, both tumours Background & Objectives: Physiological changes in the mother’s body
were filled with sebaceous material and matted hair. Cytologic investigation during pregnancy with the primary aim to support the fetus’s growth may
of ascitic fluid was negative. Pathologic evaluation of the right ovarian also suspected to worsen the natural course of various malignancies with
tumour revealed mature cystic teratoma. The left ovarian mass showed ma- even poorer prognosis then in non-pregnant women. Though borderline
ture cystic teratoma with malignant transformation to angiosarcoma. The ovarian tumours generally have an excellent prognosis, the risk of their
teratomatous component consisted of ectodermal derived skin and append- progression during gestation remain has yet to be investigated. The pur-
ages predominated with squamous epithelium and sebaceous glands. Hair pose of this study was to assess the expression of epithelial-mesenchymal
follicles, cerebral cortex, mature bone tissue, adipose tissue were also present markers, angiogenesis and the extent of natural killers in samples of
in varying proportions. While the most of the tumour demonstrated exten- ovarian borderline tumours in pregnant and non-pregnant women.
sive hemorrhagic necrosis, microscopic examination revealed atypical cells Methods: Twenty three samples [13 from pregnant (30,5±4,7 years) and
with large hyperchromatic pleomorphic nuclei. The tumour displayed sheet 10 from non-pregnant women (33,6±5,8 years)] were investigated mor-
like areas and numerous irregular vascular channels lined by atypical endo- phologically and immunohistochemically with VEGF, CD31, CD105,
thelial cells. Initial immunohistochemistry revealed strong membranous pos- CD56, E-cadherin, Vimentin, Mann-Whitney test was used for statistics.
itivity for CD34, CD31 and nuclear positivity for ERG, FLI-1 with 80% of Results: Serous borderline tumours were diagnosed more frequently in
Ki-67 index. Diagnosis was rendered as angiosarcoma arising in mature pregnant and in non-pregnant women. In addition we diagnosed
cystic teratoma based on its histologic and immunohistochemical features. endometrioid and mucinous borderline tumours with well-diffentiated
Conclusion: Angiosarcomas arising in mature cystic teratomas of the ovary components in both groups. CD31 expression in pregnant women was
are extremely rare. We experienced a case with recurred mature cystic tera- significantly higher than that in non-pregnant patients (p<0.05) with the
toma which underwent malignant transformation during an interval of 8 years median number of CD31 positive vessels 28 (range 12 – 68) and 11
since its initial surgical treatment. Although mature cystic teratoma is a benign (range 4 - 19), respectively. There were no differences in the immunore-
tumour, surgery or regular follow-up needs to be planned after due to consid- activity of all other markers among both groups (p>0.05).
eration of the risk of malignant transformation. Conclusion: Borderline ovarian tumours in pregnant women were
characterised by an enhanced CD31 expression compared with non-pregnant
patients. The increase level of CD31 expression in pregnant women is sup-
E-PS-09-052 posed to be enhanced be pregestrone activity through progestin-dependent
Small cell carcinoma of pulmonary type arising in ovarian mature angiogenesis activation. We speculate that the similarity in VEGF, CD-105,
cystic teratoma. A case report E-cadgerin, Vimentin, CD56 expression in pregnant and non-pregnant
P. Skoufogiannis1, S. Divani1, G. Kalodimos1, D. Koutsogiannis1, C. women’s indicates lack of stimulation in these agents-dependent signal path-
Barda1, A. Feritsean1 ways on borderline ovarian tumours progression complicating pregnancy.
1
General Hospital of Volos, Greece

Background & Objectives: We present a small cell ovarian carcinoma of E-PS-09-057

pulmonary type (SCCOPT) arising in a mature cystic teratoma (MCT) in Low grade endometrial stromal sarcoma of the uterus metastasis to
a 62 year-old woman. SCCOPT arising in MCT is a very rare form of the right atrium and inferior vena cava as tumour thrombus after 10
ovarian cancer. years of hysterectomy: a case report
Methods: The patient underwent a primary debulking surgery. An intra- M. Suntur1, G. Findik Guvendi1, O. Semerci1, S. Ozan Karakisi2, R.
operative cytological examination of 25ml free intraperitoneal fluid and a Bedir1
1
touch imprint cytological analysis of the left ovarian tumour where Recep Tayyip Erdogan University, Department of Pathology, Turkey,
2
performed.The tumour together with the uterus, the cervix and the right Recep Tayyip Erdogan University, Department of Cardiovascular
ovary were sent for histopathological and immunohistochemical analysis. Surgery, Turkey
Virchows Arch

Background & Objectives: Endometrial stromal sarcoma (ESS) is a rare 139.87□59.20 in EH group (P=0.024). There were significant differences
malignant mesenchymal tumour of the uterus. Endometrial stromal sarcoma in terms of PLR and NLR values.
of the uterus usually metastasis to the pelvic region. However cases showing Conclusion: EH and EPs can be differentiated before the intervention
intravascular and intracardiac metastasis even after 22 years of hysterectomy has with NLR and PLR which are simple, easily accessible, repeatable and
also been reported. Here, we describe a 52-year-old woman who presented with inexpensive methods.
right sided atrial mass and presumed inferior vena cava (IVC) thrombus which
turns out to be an endometrial stromal sarcoma.
Methods: Sections of formalin-fixed and paraffin-embedded tumour tis- E-PS-09-059
sue were stained with hematoxylin and eosin. An immunohistochemistry Fumarate hydratase deficient uterine leiomyoma: a case report
was performed. H. Sahin Ozkan1, T. Oguzsoy2, S.F. Eren1
1
Results: A 52-year-old woman was admitted to our hospital with respiratory Marmara University Faculty of Medicine, Department of Pathology,
distress. Transthoracic echocardiography revealed a mass in the IVC extends Turkey, 2 Marmara university training anad researching hospital, Turkey
into the right atrium which reported as a thrombus. Thoracic and abdominal CT
scans were also consistent with thrombus. Clinical and radiological impressions Background & Objectives: Hereditary leiomyomatosis and renal cell car-
were consistent with thrombus. The patient received anti-coagulant treatment cinoma syndrome (HLRCCS) is a rare disease caused by germline Fumarate
but did not respond to the treatment. A medical history revealed that the patient Hydratase (FH) mutation. Here, we report a case of FH-deficient leiomyoma
have had a hysterectomy 10 years ago and diagnosed with low grade endome- (FHDL) without a previously known personal and/or family history.
trial stromal sarcoma. The intravascular and intraatrial mass entirely removed. Methods: A myomectomy specimen, diagnosed with atypical uterine
On the macroscopic evaluation, a 18.5x3.2 cm tumoural mass with a tan-brown leiomyoma in another medical center was sent to our pathology depart-
and grayish cut-surface and fish-meat like appearance observed. It borrows the ment for a second opinion. The patient was 33 years old.
shape of the vessels and atrium which it occupies. Microscopically tumour Results: Gross examination revealed two masses: 1) A 4 cm myomatous
composed sheets of small monotonous cells with eosinophilic cytoplasm, mass, 2) A myomatous mass measuring 9.5 cm with some small foci of
round-to-oval nuclei and fine chromatin. There were concentric arrangement hemorrhage. Microscopic examination of the first mass showed an ordinary
of tumour cells at the perivascular site of vessels. Pleomorphism and necrosis leimyoma. The second mass was a smooth muscle tumour consisting of
were absent. A prominent myxoid changes in the focal areas of the stroma hypocellular areas with alveolar-edema and hypercellular areas. Symplastic
noted. The mitotic index was low (4 mitoses/10 HPF). atypia, prominent cherry-red nucleoli, peri-nuclear clearing, intracytoplasmic
Immunohistochemical stain revealed that the tumour was positive with eosinophilic globules, and hemangiopericytomatous vessels were the most
estrogen receptor, and CD10; and negative with desmin, HHV-8, CD117. notable findings. Mitosis was 1/10 HPF. Atypical mitosis and/or necrosis
Ki-67 proliferation index of the tumour was low (%2-3). With the help of were absent. Tumour cells were positive for SMA and negative for CD10
the overall immunohistochemical and morphologic features case diag- antibodies. Complete loss of FH immunexpression was found in the tumour
nosed as a low-grade endometrial stromal sarcoma. cells. The diagnosis was FHDL. An explanatory note was added to clarify
Conclusion: Endometrial stromal sarcoma makes up approximately that although the most FHDLs are seen sporadically, genetic testing should
0.2% of all uterine malignancies and approximately 10% of all uterine be recommended if the other risk factors for HLRCCS are present.
sarcomas. ESS is divided into low grade and high grade on the basis of the Conclusion: Uterine FHDL is a basic component of HLRCCS. While
frequency of mitoses. IVC and right atrium receives metastasis from renal evaluating atypical leiomyomas, pathologists should bear in mind the
cell carcinoma is a well-known fact. But ESS has also a potential to typical histomorphological findings of FHDL. Histomorphology is supe-
spread into IVC and right atrium. A case of ESS reoccurrence and me- rior to blind immunohistochemical screening. Approximately 1% of all
tastasis to IVC 22 years after hysterectomy has been reported in the uterine leiomyomas are FH-deficient, usually due to somatic inactivation.
literature. Our case is also emphasis this important feature ESS. In the Genetic testing for HLRCCS should not be routinely recommended to the
differential diagnosis of tumours of IVC and atrium endometrial stromal patients with FHDL in the absence of other clinical risk factors.
sarcoma also should be kept in mind both by clinicians and pathologists.

E-PS-09-060
E-PS-09-058 Uterine Mullerian Adenosarcoma: a retrospective study of 13 cases
New predictive markers for benign endometrial lesions: platelet-to- S. Ben Khalifa1, N. Abdessaied1, T. Zahmoul2, E. BelhajKhalifa2, S.
lymphocyte and neutrophil-to-lymphocyte ratio Chaieb1, B. Atika2, M. Mokni1
S. Köseoğlu1, Y. Dere2 1
Pathology Department of Fattouma Bourguiba Hospital, Monastir,
1
Mugla Sitki Kocman University Training and Research Hospital, Tunisia, 2 Department of Pathology; Farhat Hached Hospital; Sousse,
Department of Obstetrics and Gynaecology, Turkey, 2 Mugla Sitki Kocman Tunisia
University, Faculty of Medicine, Department of Pathology, Turkey
Background & Objectives: Uterine adenosarcoma is a rare tumour (8%
Background & Objectives: Endometrial polyps (EP) and endometrial of uterine sarcomas) with a dual component: a benign glandular compart-
hyperplasia (EH) are the two of the most common causes of abnormal ment and a sarcomatous stroma. The objective of this work is to report the
uterine bleeding. The aim of this study to evaluate the differentiation of EP clinical and pathological features of this tumour.
and EH in patients by using NLR and PLR which are inflammatory markers. Methods: We retrospectively analysed the clinical and pathologic data of
Methods: This retrospective study consists of 108 patients diagnosed 13 patients, initially diagnosed and treated at our institution from 1993 to
with EP and 80 patients diagnosed with EH without atypia. Ten cc of 2018. Histological confirmation of the diagnosis was obtained after biop-
venous blood sample from every patient. Hemoglobin, MCV (mean cor- sy of the tumour or after hysterectomy.
puscular volume), RDW (red cell distribution width), MPV (mean plate- Results: The median age at diagnosis was 53 years (range, 21–69 years).
let volume), numbers of lymphocytes, neutrophils, platelets, plateletcrit. The majority of patients presented with abnormal uterine bleeding (69%).
NLR end PLR values were recorded. On preoperative clinical examination, a polyp prolapsing through the
Results: NLR values were found as 2.8□2.79 in EP group and 2.2□1.30 cervix was seen in 6 patients (46%). The average tumour size was
in EH group. (P=0.022). PLR values were 157.74□83.14 in EP group and 11.2 cm (7,8 to 16 cm). Eight patients (61,5%) had stage I disease, 3
 Virchows Arch

(23%) had stage II disease, 7,6 (4%) had stage III disease, and 7,6 (3%) ovarian mucinous tumour. No patient had a cervical smear. Six cases were
had stage IV disease. Six patients (46%) had sarcomatous overgrowth, negative for p16(INK4a) in immunohistochemistry. Seven patients had
and 7 patients (53.8%) had tumours that contained heterologous elements. recurrence or metastases after initial treatment.
Death due to the disease was observed in 53,8% (7/13) of patients. Conclusion: Mucinous adenocarcinoma is a rare and aggressive form of
Conclusion: Uterine adenosarcoma is rare cancer, whose diagnostic and cervical cancer that can be confused with other pathological types.
therapeutic management are multidisciplinary as regards gynecologists,
pathologists, and oncologists. This tumour is seen especially in postmen-
opausal patients with a polymorphic symptomatology dominated by me- E-PS-09-063
trorrhagia. Its prognosis remains favorable in localized forms, of which Primary ovarian carcinoid arising in mature cystic teratoma: case
the surgery alone seems sufficient, on the other hand for the extended report
forms which are still controversial; Radiochemotherapy always retains A.C. Lisievici1, T.A. Georgescu2, M. Sajin3,4,5, R. Bohaltea6
1
their place. Carol Davila University of Medicine and Pharmacy, Bucharest,
Romania, 2 Department of Pathology, Bucharest Emergency University
Hospital, Romania, 3 SUUB, Romania, 4 UMF Carol Davila, Romania,
5
E-PS-09-061 European Society of Pathology, Romania, 6 Department of Obstetrics
Agressive angiomyxoma of the vulva: a report case and Gynaecology, Emergency University Hospital Bucharest, Romania
S. Yacoub1, S. Mistiri1, D. Chiba1, T. Tlili1, N. Abdessayed1, M. Mokni1
1
Department of Pathology Farhat Hached Hospital, Tunisia Background & Objectives: Carcinoids are rare neuroendocrine tumours
with an incidence of 1 to 2 cases per 100,000 patients. Primary ovarian
Background & Objectives: Aggressive angiomyxoma (AA) is a rare, carcinoids account for less than 1% of all carcinoid tumours and less than
locally aggressive mesenchymal tumour of the perineum, affecting more 0.1% of all ovarian neoplasms, being so rare that a clinician may not
frequently women. its aggressiveness is local, reflecting its infiltrating encounter even one during his or her entire medical career.
character and its tendency to recurrence. Methods: We report the case of a postmenopausal 64-year-old female
We describe the clinical and pathological characteristics of an aggressive presenting to the Emergency University Hospital in Bucharest, Romania
angiomyxoma of the vulva. due to lower abdominal pain. CT examination revealed a large, well-
Methods: A 40-year-old woman with no previous history, consulted for a defined, bilobed solid and cystic mass of the left ovary, with no detectable
swelling of the large right lip of the vulva. A surgical resection was performed. ascites. The patient underwent bilateral salpingo-oophorectomy.
Results: The resected specimen showed a polypoid tumour of 5 cm long axis Results: Gross aspect of the left adnexa and subsequently examined frozen
fixed to a pedicle of 1.3 cm. The surface was greyish without any ulcer or sections were suggestive for mature cystic teratoma. Careful postoperative
erosions. Histological examination showed a mesenchymal proliferation, of histopathological examination of the solid areas revealed a mixed-type carci-
low to moderate cell density. It was made of stellate or elongated fibroblastic- noid (insular and trabecular) arising in the background of a mature cystic
like cells. The stroma was loose, myxoid full of capillaries and venules of teratoma. The tumour was limited to the left ovary, without rupturing the cyst
variable size. There were scalloped with regular endothelial lining. The skin wall (T1a). Ancillary tests revealed immunoreactivity for synaptophysin,
surface was regular, non-ulcerated. the surgical boundaries were tumour-free. chromogranin and a low Ki-67 proliferative index (<1%). ER, PR and
Conclusion: AA is a locally aggressive rare mesenchymal tumour of the CDX2 were negative. The right ovary was unremarkable.
pelvis, expressing the hormone receptors. Surgical removal is the main Conclusion: In the absence of other teratomatous elements, primary
treatment. The use of hormonal treatment during recurrences is being ovarian carcinoids may be difficult to distinguish from metastatic carci-
evaluated and shows in some cases encouraging results. noids. Carcinoid syndrome may develop in the absence of liver metasta-
ses. Diagnosis should always be confirmed by immunohistochemistry
and extensive sampling of any solid area within a mature teratoma is
E-PS-09-062 emphasized, in order to minimize the risk of missing a focus of carcinoid.
Mucinous adenocarcinoma of the uterine cervix: clinicopathological
study of 8 cases
M. Manai2, G. Sahraoui2, R. Doghri1, R. Sallami2, H. Guizani2, K. E-PS-09-064
Mrad1, L. Charfi1, M. Driss1 Hormone receptor end p16 immunohistochemical expression in dis-
1
Department of Pathology, Salah Azaiez Institute, Tunisia, 2 Salah Azaiez tinction between endometrial and endocervical adenocarcinoma
Institute, Tunisia R. Narjess1, N. Boujelbene2, M. Driss2, R. Doghri2, I. Abbes2, H. Azaiz2,
N. Ben Hamida2, K. Mrad2, L. Charfi2
1
Background & Objectives: Adenocarcinoma is the second type of cervical Institut of Carcinology Salah Azaiz Tunis, Tunisia, 2 Department of
cancer accounting for 20–25% of all cervical cancers. Mucinous adenocarcinoma Pathology, Salah Azaiez Institute, Tunisia
was redefined in 2014 WHO classification into different subtypes: gatric type,
intestinal type and signet-ring cell type. The aim of this study is to describe the Background & Objectives: Primary endometrial (EmA) and endocervi-
clinicopathological characteristics of these various subtypes of cervical cancer. cal (EcA) adenocarcinoma are recognized as distinct entities, with differ-
Methods: This was a retrospective descriptive study of patients diag- ent etiologies, behavior and treatments. Sometimes, distinction between
nosed between 1 January 2010 and 31 December 2016 in one cancer them is often difficult in limited diagnostic specimens such as biopsies or
institute. All the cases of cervical adenocarcinoma were defined as mu- curettage specimens. We investigated the value of a panel of antibodies, to
cinous adenocarcinoma according to 2014 WHO classification. We distinguish between primary EmA and EcA.
analysed their clinical and pathological characteristics. Methods: We use a panel of immunohistochemical stains including es-
Results: Among the 38 cases of cervical adenocarcinoma, 8 (21%) were trogen receptor (ER), progesterone receptor (PR) and p16 in a series of
diagnosed as mucinous. Five were intestinal type, one was of gastric type, cervical biopsies presenting considerable overlap in the morphological
two were signet-ring cell type. The patients’ mean age was 48 years and 6 features of adenocarcinoma arising in the two sites mentioned above.
patients were premenopausal. The revealing symptom was metrorrhagia Results: Twenty-eight biopsies were evaluated. They concern 20 EmA
in seven cases and (38%) and pelvic pain whose exploration revealed an and 8 EcA. The great majority of EmA (77.7%) express ER but no case of
Virchows Arch

EcA express ER (p=0.001). Likewise, PR was expressed in most EmA Results: The immunohistochemical study indicated RIG-1 staining in
(73.3%) and no case of EcA (p=0.001). placental villi: amnion cells, endothelium, decidual cells, cyto-and
Seventy-five percent of EmA display variable patchy p16 expression, syncytiotrophoblast, syncytial knots, stroma cells. RIG-1 demonstrated
only 1 case show extensive p16 expression. All EcA show diffuse nuclear significantly higher expression in syncytiotrophoblast (17+4) in LC
p16 expression (p<0.0001). group than in the other studied groups EC (8+3), EPE (9+4) and LPE
Conclusion: We conclude that ER, PR and p16 are useful immunohisto- (11+3), (р<0.01). Compare to LC group RIG-1 expression were at 47%
chemical markers in distinguishing EmA and EcA. The "classic" endo- higher than in EC, 52.9% higher than in EPE, and 62.7% higher than in
metrial adenocarcinoma will be positive for ER, PR and show weak or LPE group (p<0.01). Decreased RIG-1 expression probably contributes
patchy p16. In contrast, the "classic" endocervical adenocarcinoma will to the development of pro-inflammatory response and PE.
be strongly and diffusely positive for p16 but negative for ER, and PR. Conclusion: Thus, down regulated in syncytiotrophoblast RIG-1 expres-
This distinction is important to make because the different therapeutic sion in PE confirmed pro-inflammatory trophoblast phenotype and may
management and prognosis. be one of the predisposing factor for preeclampsia.

Funding by the Grant of the President for leading scientific schools (NS-
E-PS-09-065 4566.2018.7, Agreement 075-02-2018-519).
Vulvar sarcoma: a single institution experience
M. Manai1, R. Doghri2, G. Sahraoui1, R. Sallami1, D. Kacem1, K. Mrad2,
M. Drisse2, L. Charfi2 E-PS-09-068
1
Institute Salah Azaiez, Tunisia, Morphological effects of chemoradiation therapy on cervical
2
Department of Pathology, Salah Azaiez Institute, Tunisia adenocarcinoma
A. Candaele1, J. Van Dorpe1, E. De Jaeghere1, P. Tummers1, A. Makar1,
Background & Objectives: Sarcomas of the vulva comprise approxi- P. De Visschere1, H. Denys1, K. Vandecasteele1, K. Van de Vijver1
1
mately 1–3% of all vulvar cancers, with leiomyosarcomas, epithelioid sar- Ghent University Hospital, Belgium
comas, and rhabdomyosarcomas being the most common among them.
The aim of this study is to report our incidence of sarcoma at this site and Background & Objectives: The Study group included 10 women with a
to emphasize the broad differential diagnosis and the prognostic factors. histological diagnosis of advanced cervical adenocarcinoma, receiving neo-
Methods: All patients with a diagnosis of vulvar sarcoma at the department adjuvant chemoradiation therapy followed by radical surgery. The aim for
of pathology of Salah Azaiez Institue over a period of 25 years (1993 - 2018). the present study is to evaluate the responsiveness to chemoradiation and to
Clinical, histopathological and immunohistochemical features were recorded. identify pathologic changes that occur during treatment and systems for
Results: Six vulvar sarcomas were diagnosed during this period: rhabdomyo- evaluating response to treatment and its effect on long-term survival.
sarcoma (n = 2), leiomyosarcoma (n=1), epithelioid sarcoma (n=1), Methods: Pathological response to treatment was evaluated by the pres-
dermatofibrosarcoma (n=1), and carcinosarcoma (n=1). The age ranged from ence of residual neoplastic tissue, fibrosis, calcifications, necrosis, inflam-
2 months to 56 years. The rhabdomyosarcomas were of embryonal-type and matory infiltrates, foamy macrophages, foreign body-like giant cells,
were diagnosed at early childhood (2-16months). All the cases were clinically acellular pools of mucin and pleomorphic neoplastic nuclei.
present as a non-specific tumour mass. The tumour size ranged from 30 to Results: 9 out of 10 women responded partially or well to neo-adjuvant
80mm. The diagnosis was made on biopsy in all cases. Immunohistochemistry chemoradiation therapy. In the patients that responded we can distinguish
was necessary to classify these sarcomas. A vulvectomy was performed in 3 3 groups with different morphological features. A first group showed little
cases (Dermatofibrosarcoma, epithelioid sarcoma, carcinosarcoma) with neg- response with nearly no fibrosis or inflammation, resulting in expanded
ative microscopic margins in only one case (dermatofibrosarcoma). network of infiltrating small and angulated glands. The second group
Chemotherapy was indicated in rhabdomyosarcomatous cases. having an excellent response, was associated with expanded acellular
Conclusion: Sarcomas of the vulva are rare malignant neoplasms that pools of mucin with little remaining tumour glands. A third group showed
often lead to misdiagnosis.It is important to consider them in the clinical a good response with an altered eosinophilic morphology of the remain-
differential diagnosis of non-specific vulvar lesions, in order to establish ing tumour nests.
an early accurate diagnosis and appropriate treatment. Conclusion: Identification of predictive markers associated with a good
survival may prove clinically useful and implement an individualized
treatment plan.
E-PS-09-066
RIG-1 is down regulated in placental tissue in cases of early - and late
- onset preeclampsia E-PS-09-070
N. Nizyaeva1, M.N. Nagovitsyna1, E.Y. Amiraslanov1, N.A. Lomova1, A unique presentation of blue nevus: a patient with endocervical
S.V. Pavlovich1 location
1
V.I.Kulakov National Research Center for Obstetrics, Gynaecology and R. Yilmaz1, R. Bedir2, O. Semerci2
1
Perinatology of Ministry of Healthcare of the Russian Federation, Sanliurfa Siverek Community Hospital, Turkey,
2
Moscow, Russia Recep Tayyip Erdogan University Deparment of Pathology, Turkey

Background & Objectives: The objective was to study in placental Background & Objectives: Blue nevi, composed of spindle-like den-
samples in cases of early–(EPE) and late – onset (LPE) preeclampsia. dritic melanocytes, are benign lesions usually located on the reticular
Methods: Groups with PE included 12 women with EPE and 8–with dermis of the skin and rarely located on mucous membranes. The
LPE. Control groups consist of 10 women with normal pregnancy, 38- endocervical blue nevus is a rare benign lesion which can be incidentally
39 gestation weeks (late control–LC), and 10 – 26-30 weeks (early con- found in hysterectomy specimen. Since this is a very rare condition, we
trol–EC). We performed histological (hem&eosin) and immunohisto- intended to report it in the literature.
chemistry studies on the paraffin-embedded slices of placenta, taking Methods: A 54-year-old female patient with a long history of menorrha-
after cesarean section, using RIG-1 primary polyclonal antibodies gia was admitted to Obstetric and Gynaecology clinic. The patient had
(1:500;GenTex). The intensity of immunohistochemical reaction was es- intramural leiomyoma in the radiologic examination. The patient
timated by means of microscope imaging software NIS-Elements. underwent the surgical procedure of total abdominal hysterectomy.
 Virchows Arch

Results: We observed an endocervical polyp and a hyperpigmented area Results: Macroscopic examination showed a fleshy and yellowish polypoid
under this polyp on macroscopic examination. Histological examination re- mass measuring 3,3 cm in the first case and 8,5cm in the second. No necrosis
vealed benign, pigmented, dendritic spindle cells between endocervical or hemorrhage were observed. The two tumours shared the same histological
glands in the stroma of the uterus cervix. The dendritic spindle cells were features, of a biphasic tumour, formed by a malignant stroma, with moderate
immunoreactive for S100 and HMB45. The pigment showed a positive re- to high density. Mesenchymal cells were elongated myofibroblastic-like with
action to Fontana-Masson histochemical stain. Melanin pigment in the basal low to moderate atypia. Periglandular cuffing of the stromal cells around
epithelium was not observed in the endocervix. There was no junctional compressed or cystically dilated benigne endometrial glands, displaying
activity in the endocervix. There were no increased typical-atypical mitotic focally progesterone impregnation. Immunohistochemistry was performed
activity, pleomorphism and necrosis. We reported this case as a blue nevus. in only one case and showed Smooth muscle actin (SMA) expression by
Conclusion: Blue nevi of endocervix are usually found incidentally in stromal cells and negativity of desmin and H-caldesmon.
hysterectomy specimens, and they are usually located in the stroma of the Conclusion: Adenosarcoma of uterus is a biphasic tumour of generally
cervix. When located on the endocervix, the blue nevus might be confused low malignant potential. A complete and Monobloc surgical resection is
with other benign or malignant lesions. Although the blue nevi seem to be the ideal therapeutic option.
lesions of low clinical significance, they require careful differential diagnosis
with malignant melanoma, especially in scanty endocervical curettage or
cervical biopsy specimens. Herein, we reported a case with endocervical E-PS-09-076
blue nevus presented as an endocervical polyp, which is a rare phenomenon. Sex cord-stromal tumours of the ovary: clinicopathological and ge-
netic analysis
C. Bartosch1, S. Alves2, M. Pinheiro3, M. Farinha1, F. Pereira2, J. Costa1,
E-PS-09-071 F. Silva1, R. Santos3, A. Peixoto3, S. Sousa2, A. Petiz4, M.R. Teixeira3, D.
Epithelioid leiomyosarcoma with glandular-like pattern Pereira2
Y. Rogov1, N. Kornev2, A. Syantovich2, O. Solodkaya2, Y. Kuzmenka- 1
Department of Pathology IPOP, Portugal, 2 Department of Oncology
Maskvina1, V. Zubovich2, E. Grigorieva1 IPOP, Portugal, 3 Department of Genetics IPOP, Portugal, 4 Department
1
Belarusian Medical Academy of Postgraduate Education, Belarus, of Gynaecology IPOP, Portugal
2
City Clinical Pathology Bureau, Belarus
Background & Objectives: Sex cord-stromal tumours are a heteroge-
Background & Objectives: Epithelioid leiomyosarcoma differs from neous group of rare neoplasias, with variable biological behavior. This
ordinary spindle cell leiomyosarcoma by rounded or polygonal cells with study aims to describe the clinico-patological features of a series of patients
eosinophilic or clear cytoplasm. They may be arranged in sheets, cords, with pure sex cord tumours and mix sex cord-stromal tumours of the ovary.
trabeculae, nests. We report a case of recurrent leiomyosarcoma with Methods: Retrospective cohort study of a series of patients with sex cord-
unusual glandular-like pattern. stromal tumours of the ovary, managed at Portuguese Oncology Institute
Methods: A 71-year-old female patient was hospitalized with recently of Porto (1994-2018). We collected clinical data, reviewed histological
appeared abdominal pain. 8 years ago, she underwent combined treat- material and performed FOXL2 gene mutations analysis.
ment for uterine leiomyosarcoma. Clinical examination revealed tumour Results: Initially we included 41 patients, but only 34 had available histo-
nodes in the greater omentum, mesentery of the small intestine and peri- logical material. After histological review, tumour subtype changed in 6
toneum measuring 4.0, 2.0 and 2.0 cm in diameter. They were removed, patients and one was excluded. We included in the analysis 33 patients, with
an d ti ss u e s amp le s wer e in v es ti ga te d h i st ol o gi cal ly a nd a median age at diagnosis of 53 (4-79) years. Histological subtypes included
immunohistochemically. 18 adult granulosa cell tumours (TCGA), 9 Sertoli-Leydig cell tumours
Results: Microscopic evaluation of all tumour nodes revealed an epithelioid (TCSL), 2 Sertoli cell tumours and other (n=4). We identified FOXL2 gene
leiomyosarcoma with areas of conventional type. Tumour cells were predom- mutations in 14/29 patients, of which 13/16 (81%) corresponded to TCGA,
inantly rounded, with eosinophilic cytoplasm. They focally formed glandular- and 1 TCSL. The majority (87.9%) was diagnosed as FIGO stage I. Ten
like structures, lining the gaps in one or several rows. These sites looked like patients had recurrences and 6 died of the disease.
adenocarcinoma. Immunohistochemical staining was positive for SMA, Conclusion: Our series clinico-pathological features are in accordance
Desmin, WT1 and negative for CK, GLUT1, BerEP4, Calretinin, ERG, with previous studies, emphasizing the variability in clinical presentation
CD31, CA125, CD117, DOG1, PAX8. Mitotic activity was high. Epithelioid and morphology of these tumours. The frequency of FOXL2 gene muta-
leiomyosarcoma recurrence with glandular-like pattern was diagnosed. tions is also concordant with that reported in the literature. This study
Conclusion: Epithelioid leiomyosarcoma occasionally can form pseudo- highlights the need for central review and reinforces the diagnostic utility
glandular structures that can be regarded as adenocarcinoma. Histological of FOXL2 gene mutations.
signs of myoid differentiation in tumour and immunohistochemistry help
make the correct diagnosis. We could not find similar descriptions in the
available literature. E-PS-09-077
A review of the morphologic features of endometrial hyperplasia
without atypia, complex after progesterone therapy
E-PS-09-072 S. Noh1, E. Shin2, J. Kim2, J.Y. Shim2
1
Uterin mullerian adenosarcoma: an unusual tumour of the uterus CHA Gangnam Medical Center, CHA University School of Medicine,
S. Yacoub1, M. Sara1, D. Chiba1, N. Abdessayed1, B. Sriha1 Republic of Korea, 2 CHA University School of Medicine, Republic of
1
Department of Pathology Farhat Hached Hospital, Tunisia Korea

Background & Objectives: Uterine Mullerian adenosarcoma is an uncom- Background & Objectives: Endometrial hyperplasia without atypia is a
mon biphasic tumour composed of a malignant stromal component and benign precursor of endometrial carcinoma. Well differentiated endometrial car-
epithelial component. It was originally described in 1974 and is considered of cinoma occurs in 1-3% of women with hyperplasia without atypia.
low malignant potential. We report 2 rare cases of Mullerian adenosarcoma. Because of retaining fertility, women with endometrial hyperplasia or
Methods: There were two women of 23 and 43 years old, presented clin- early stage endometrial carcinoma want to manage with conservative
ically with vaginal bleeding. Clinical examination showed a polypoid mass Progesterone therapy. However, Progesterone therapy changes the endo-
projecting through the cervix. A polypectomy was performed in both cases metrial morphology and gives pathologist difficulties. To help determine
Virchows Arch

1
the therapeutic effect, we aimed to review and list common morphologic Belarusian Medical Academy of Postgraduate Education, Belarus,
2
features that can distinguish residual complex endometrial hyperplasia City Clinical Pathology Bureau, Belarus
without atypia from Progesterone effect. Because the degreee of nuclear
atypia is difficult to make intuitive judgment, we reviewed the complex Background & Objectives: Aggressive angiomyxoma is a rare myxoid
hyperplasia without atypia with the greatest morphological diversity. mesenchymal tumour of the pelvis and perineum, which is not included in
Methods: Endometrial curettage and/or biopsy samples that were diag- the latest WHO Classification of tumours of the uterine corpus since it
nosed with complex hyperplasia without atypia and had three or more was found in this location in exceptional cases. Morphological diagnosis
follow-up curettage and/or biopsy of the uterine endometrium from 2008 may be difficult, since the tumour is similar to various myxoid sarcomas.
to present were searched from the database of the Department of Pathology, We report our observation of this neoplasm.
CHA Gangnam Medical Center. Fifty-two cases diagnosed with complex Methods: A 58-year-old woman was hospitalized with complains of acute
hyperplasia without atypia were retrieved, but 12 cases were excluded minor vaginal bleeding for some days. The patient was in menopause for 10
because material insufficiency due to either therapeutic effect or sampling years. The examination revealed a submucous node in the body of the
error. Thus, 40 cases were finally included in the review. uterus 5,5 cm in diameter. Structures suspected of sarcoma were found in
Results: Of the retrieved 40 cases, the most frequent morphologic features of curettage tissue samples. After radical hysterectomy, a macroscopic, histo-
complex hyperplasia without atypia after Progesterone treatment were papil- logical and immunohistochemical study of this tumour was performed.
lary configuration in all cases. All cases turned into dull and blunt shape on Results: The tumour had a soft gelatinous appearance with small hemor-
follow-up. The helpful features were residual or new squamous morule. The rhages on cut sections and predominantly well-defined margins,
reasons for misclassification of nuclear atypia were eosinophilic metaplasia, unencapsulated. Microscopically it was highly myxoid, composed of uni-
after hormonal therapy, similar to apocrine metaplasia in the breast. Two cases form, small, stellate and spindle shaped cells with indistinct borders,
of mucinous metaplasia, similar to endocervical glands of uterine cervix can without pleomorphism, necrosis and significant mitotic activity.
be misdiagnosed as carcinoma, because of their architectural complexity. Cellularity was low to moderate. Vessels of various sizes were regularly
Conclusion: Although advances in medical technology have increased the present, some of them with thick muscular walls. Immunohistochemical
number of people receiving Progesterone treatment, there are still rare reports staining was positive for Desmin, Vimentin, ER, PR, weakly positive for
of changes in morphology after Progesterone therapy. However, false-positives CD34 and negative for MyoD1, S100, SMA. Ki67 reached about 5-10%
or false-negative cannot be avoided to some extent. Identifying papillary con- (up to 20% in “hot spots”). An aggressive angiomyxoma was diagnosed.
figuration and squamous morule has a merit in itself in that it often leads to the Conclusion: Aggressive angiomyxoma can sometimes be found in the
identification of underlying complex hyperplasia without atypia. body of the uterus. The diagnosis of this tumour in the study of curettage
biopsies is difficult. It should be considered in the differential diagnosis of
uterine myxoid lesions.
E-PS-09-078
A morphometric study of hypoxic and vascular changes of chorionic
villi in maternal vascular malperfusion Sunday, 8 September 2019 – Wednesday, 11 September 2019
D. Obradovic1, R. Jankovic1, J. Jevtic1, D. Opric1 E-PS-10 | Haematopathology
1
Faculty of Medicine, University of Belgrade, Serbia
E-PS-10-001
Background & Objectives: Maternal vascular malperfusion (MVM)
Angioimmunoblastic T-cell lymphoma in patient with plasm cell my-
represents altered uterine and intervilous blood flow resulting in recog-
eloma. Case report and review of the literature
nizable hystological pattern of placental hypoxic injury with potential
A. Abuomar1, T. Lopez1
adverse effect on fetus. MVM is frequently found in pregnancies compli- 1
Hospital General Universitario de Elda, Alicante, Spain
cated by preeclampsia and intrauterine growth restriction.
Being that MVM is vascular and hypoxic phenomenon affecting
fetoplacental exchange we analysed a level of vascularisation of chorionic Background & Objectives: Angioimmunoblastic T-cell lymphoma (AITL),
villi and level of intravillous fibrosis. a subtype of mature peripheral T cell lymphoma, is a neoplasm of mature T
Methods: Five placentas with MVM were morphometricaly analysed. folicular helper characterised by a systemic disease involving lymph nodes
Inclusion parameters were syntitial knots present in 30% or more terminal (LN). AITL has a typical morphological, immunohistochimical (IHQ) and
villi, retroplacentar haematoma and weight of placenta under 10th percen- molecular signature. Usually affects older people with a poor prognosis.
tile for week of gestation. Materials were obtained from autopsy Rarely associates with B cell neoplasm, exceptionally with plasm cell myeloma
speciments at Institute of Pathology, Medical Faculty in Belgrade. (PCM) with few cases reported in the literature to the best of our knowledge.
Formalin fixed paraffin embedded tissues were stained with Masson- Methods: A 72 years old man with PCM with high risk cytogenetics, on
Trichrome stain for evaluation of fibrosis and blood vessels were marked treatment, and chronic renal faillure was admitted to our hospital with
with CD34 antibody. All images were analysed using Fiji software. persisted fever, skin rush, generalized lymphadenopathy and positive
Statistical analysis was performed using Microsoft Excel software. polymerase chain reaction (PCR) and immunoglobulin M for Epstein-
Results: Results of statistical analysis have shown trend of correlation Barr virus (EBV). No improvement was seen after a few weeks of symp-
between higher level of vascularisation of chorionic villi with increase of tomatic treatment. Lymphadenectomy of an enlarged axillary lymph node
deposition of intravillous fibrin. Analysis haven’t shown statistical sig- was done rule out a possible lymphoproliferative disorder.
nificance which may be expected due to small sample. Results: LN with total effacement of morphology, prominent vascularity
Conclusion: We believe these observations should shed some light on the way with arborization of high endothelial venuls (HEV), a proliferation of small
of thinking about fibrosis of chorionic villi. We are of opinion that perhaps to medium size atypical lymphocytes with clear cytoplasm and distinct cell
deposition of intravillous fibrin shouldn't be observed as strictly degenerative, membrane in an inflammatory back ground. No cells of Hodgkin or Reed–
but instead as positive reactive change as part of adaptation to hypoxia in placenta. Sternberg morphology were seen. IHQ: CD3, CD4, BCL6, CD10, ICO,
PD1 and CXCL13. Few cells expressed CD20+, CD30+. EBER1+ cells
were seen. CD23 revealed a marked folicular dentritic cell proliferation
E-PS-09-079 entrapping HEV. TCR gene rearrangement were clonal.
Aggressive angiomyxoma of the uterus: a case report Conclusion: Typical morphological, IHQ and molecular characteristics
Y. Rogov1, N. Kornev2, Y. Kuzmenko-Moskvina1, A. Syantovich2, S. of AITL are diagnostic in the majority of cases, however, realizing a
Budanova2 differential diagnosis with Reactive T Zone Hyperplasia,
 Virchows Arch

Angiofollicular Lymphoid Hyperplasia (Castleman Disease), Plasma Cell 10-25%, 25-50%, 50-75% or 75-100%. Cases with at least 2+ positivity
Type, Peripheral T Cells Lymphoma NOS, T-cell/histiocyte-rich B-cell were further examined with an extended cytokeratin panel.
Lymphoma and Hodgkin Lymphoma is mandatory. It is recommended to Results: 41 AML and 9 ALL cases were included. The reproducibility of 1+
report percent of CD30+ cells since target therapy is available. staining was very poor (AE1/3 κ = 0.16, MNF116 κ = 0.13) and so only 2+/
3+ staining was considered positive. Three of the AML cases (7.3%) showed
at least 2+ staining with AE1/3 or MNF116, which was cytoplasmic and dot-
E-PS-10-002 like in character, involving at least 10% of the tumour cells. One case showed
Retroperitoneal and kidney infiltration with anaplastic plasm cell 3+ MNF116 positivity in 50-75% of tumour cells and also had 3+ staining
myeloma simulating an obstructive acute renal failure. Case report with CAM5.2.
and literature review Conclusion: Cytokeratin expression in acute leukaemia is uncommon,
A. Abuomar1 but not rare (7.3% of all AML cases in this retrospective study), and can
1
Hospital General Universitario de Elda, Alicante, Spain be strong and diffuse. Leukaemia can present at extramedullary sites,
where cytokeratins may be included in a broad immunohistochemical
Background & Objectives: Anaplastic plasm cell myeloma (APCM) is panel for work-up of a poorly differentiated malignant neoplasm.
a rare, highly aggressive and treatment-resistant subtype of plasm cell Pathologists should be aware of the potential pitfall in this scenario.
myeloma (PCM) with Identical morphological and Immunohistochemi-
cal (IHQ) findings to plasmoblastic lymphoma (PL). We report, up to our
knowledge, the second case in literature with clinical presentation of an E-PS-10-004
obstructive acute renal failure duo to retroperitoneal and renal infiltration. Histomorphologic evaluation of bone marrow involvement in mantle
Methods: A 67 years old immunocompromised heart transplant man was cell lymphoma and its correlation with flowcytometric
admitted to nephrology department with a clinical picture of obstructive acute immunophenotyping
renal failure. CT scan suggested metastatic urethral carcinoma showing multi- S. Sharma1, S. Yadav1, K. Rahman2, M. Murari1
1
ple retroperitoenal nodular masses with infiltration of left kidney and ureter, Department of Pathology, SGPGIMS, Lucknow, India,
2
dilatation of renal chalices, enlarged retroperitoneal and hiliary adenopathy. Department of Clinical Haematology, SGPGIMS, Lucknow, India
Bone marrow aspiration showed sheets of anaplastic plasma cells.
Monoclonal serum and urine immunoglobulins were detected. A total nephrec- Background & Objectives: Mantle cell lymphoma (MCL), accounts for
tomy was performed as a suspicious of metastatic urtetral neoplasm persisted. approximately 3-10% of Non-Hodgkin lymphomas. It is usually com-
Results: Gross examination showed a multiple perirrenal nodular masses of posed of monomorphic small to medium-sized lymphoid cells and needs
1-5cm which extrinsically infiltrated left renal parenquima and proximal to be distinguished from other small B - cell lymphoproliferative diseases
ureter simulating intraurethral neoplasm with stenosis.Microscopic study i.e. CLL, B - PLL, follicular lymphoma and marginal zone lymphomas.
showed a monomorphic diffuse proliferation of large cells with plasmoblastic The aim of the study was to analyse the prevalence of bone marrow
appearance,multinucleated plasmoblast,multiple mitosis and numerous apo- involvement and correlate histomorphologic findings with flow cytomet-
ptotic figures were seen, with a starry sky appearance.Small cells with ric analysis in a series of patients with MCL.
plasmocytoide appearance were seen.IHQ:CD138+,CD79A+,CD56+ Methods: We retrospectively analysed 26 consecutive patients of MCL
,MUM1+,CD20-,CD10-, LMP1-,PAX5-,CD45-,ALK-,HHV8-, EBER1+ diagnosed over a period of 3 years for bone marrow (BM) involvement.
Bone marrow monoclonal aberrant plasm cells with 1q21 amplification BM involvement was assessed by conventional morphology, IHC and
and 14q32 IGH rearrangement confirmed the diagnosis of APCM. Patient flow cytometry (FC) in BM aspirate and trephine biopsy specimens.
died duo to gastric cancer. Results: MCL comprised 13.7% of all Non-Hodgkin’s lymphomas with BM
Conclusion: In the setting of immunodeficiency, APCM and PL can be involvement. BM involvement was identified in 22 trephine biopsies. The extent
associated with EBV, thus making differencial diagnosis always challeng- of lymphomatous infiltration ranged from 10-90%. Diffuse pattern of infiltration
ing and sometimes impossible. The diagnosis of APCM should base on was seen in 10 cases. All cases were positive for CD5, CD20, and negative for
clinico-morphological, IHQ and molecular findings. Serum/urine mono- CD23 on both FC and IHC. Cyclin D1 was positive in all cases on IHC. There
clonal immunoglobulins is vital for the diagnosis, though patients with was a significant correlation between percentage marrow infiltration on BM
PCM can develop lymphproliferative disorders including PL. histology and FC (Spearman’s correlation coefficient 0.67, p-value 0.014).
Conclusion: Bone marrow involvement was found in majority of patients
with MCL. Bone marrow involvement was associated with high circulat-
E-PS-10-003 ing lymphocyte count and serum LDH levels. The histomorphologic
Cytokeratin expression in acute leukaemia: a potential pitfall findings in BM trephine correlated with flow cytometric analysis.
J. Garry1, E. O'Driscoll1, R. Werner1, A. Connolly1, B. Hayes1
1
Cork University Hospital, Ireland
E-PS-10-005
Background & Objectives: Cytokeratin expression is characteristic of Lollipops and onions: Castleman disease-like changes in malignant
carcinomas but is thought rare in haematological malignancies. While lymphoma - comparison with true Castleman disease and IgG4-
several studies have examined cytokeratins in mature lymphoid neo- related lymphadenopathy
plasms, and several case reports describe cytokeratin expression in acute M. Válková1, K. Kamaradua1
1
myeloid leukaemia (AML), no systematic assessment has to our knowl- The Fingerland Department of Pathology, Charles University Faculty of
edge been previously reported in AML or in acute lymphoblastic leukae- Medicine and University Hospital in Hradec Kralove, Czech Republic
mia (ALL). We aimed to assess expression of cytokeratins by immuno-
histochemistry in a series of bone marrow trephine biopsies from patients Background & Objectives: Morphological features of hyaline vascular
with acute leukaemia. type of Castleman disease include atrophic germinal centers, prominent
Methods: Fifty bone marrow biopsy specimens from 2013-2017, mantles with onion skinning and increased vascularity with penetration of
SNOMED coded as “acute leukaemia” were selected from our files. vessels into germinal centers (lollipops). Similar patterns can be seen in a
Original H&E slides were retrieved, new sections stained with MNF116 subset of IgG4-related lymphadenopathy and in rare cases of malignant
and AE1/3, and all slides reviewed by a consultant and a trainee pathol- lymphoma causing a possible diagnostic pitfall.
ogist. Cytokeratin expression in tumour cells was graded semiquantita- Methods: Eleven cases were retrieved from the archive using keyword
tively from 0 to 3+. The number of cells staining was recorded as 1-10%, search for lymph nodes with Castleman disease-like features. All cases
Virchows Arch

3
have been reviewed with focus on distinguishing malignant and benign Surgery Department, Holy Family Hospital, Nazareth, Israel,
4
lesions. Additional testing was performed in all cases including basic Institute of Haematology, Assuta Medical Center, Tel Aviv, Israel,
5
immunohistochemical panel (CD20, CD23, bcl-2, CD5, cyclin D1, Pathology Department, Sourasky Medical Center, Tel Aviv, Israel
Ki67, CD10, bcl-6, immunoglobulin light chains and IgG4).
Results: Out of eleven cases, five cases presenting with partial or fully Background & Objectives: Histiocytoses are rare heterogeneous mono-
developed Castleman disease-like features were lymphomas including three nuclear phagocytes derived neoplasms. Two of the more recognized
cases of follicular lymphoma and two cases of mantle cell lymphoma. hystiocytoses are Langerhans cell histiocytosis (LCH) and Erdheim-
Immunohistochemistry was crucial for establishment of diagnosis of ma- Chester disease (ECD). Both entities often harbor the BRAFV600E muta-
lignant lymphoma. Four cases fulfilled morphological criteria of probable tion, which may be the link between them. The coexistence of LCH with
IgG4-related lymphadenopathy with high numbers of IgG4+ plasma cells. ECD is infrequent and is referred to as mixed LCH/ECD. Here we de-
Two cases with prominent fully developed changes were classified as idi- scribe an unusual case of ECD patient who developed cholelithiasis as-
opathic multicentric Castleman disease after thorough clinical investigation. sociated with LCH infiltrate in the gallbladder.
Conclusion: Presence of Castleman disease-like features is not always Methods: The medical records, imaging tests and pathological findings
diagnostic just of Castleman disease. In our series, they were observed of a 34 years old patient have been studied and are presented. The patient
more frequently in other disorders, namely malignant lymphoma (where went through cholecystectomy due to cholelithiasis. Three years before
only part of the lymph node is usually involved) or IgG4-related lymph- he was diagnosed with ECD based on characteristic clinical-radiological-
adenopathy. Awareness of these changes is crucial and combination with pathological features. His presentation included multifocal disease in-
immunohistochemistry and molecular studies can help to avoid a possible volvement of the hypophysis with central diabetes insipidus, lower ap-
misdiagnosis. pendicular skeleton inducing pain and mesenteric fat infiltrates causing
abdominal ache. Imaging revealed the typical "hairy kidney" and bone
The work was supported from Fund-Project BBMRI-CZ, No: EF16 013/ biopsy supported the diagnosis as well.
0001674. Supported by the programme PROGRES Q40/11. Supported Results: The resected gallbladder showed distorted structure with thick-
by the project BBMRI-CZ LM20150. ened wall and cholelithiasis. Microscopic examination identified promi-
nent mucosal infiltrate of histiocytes having irregular nuclei with occa-
sional grooves, accompanied by numerous eosinophils. On immunostains
E-PS-10-006 the histiocytes showed positive staining for CD68, CD1a, S100 and
An unusual case of BCL-2, BCL-6, CD10 & MUM-1 quadruple neg- langerin. Overall, the morphological features and immunostain results
ative follicular lymphoma were consistent with LCH. In contrast, the left tibia biopsy preformed 3
S. Shawash1, N. Abdullah1 years before showed infiltrate of CD68 positive, CD1a negative and S100
1
King Hussain Cancer Center, Jordan negative histiocytes that supported the diagnosis of ECD.
Conclusion: Altogether features reflect co-occurrence of ECD and LCH,
Background & Objectives: Nodal follicular lymphoma originates in otherwise named mixed LCH/ECD. Not only this is a rare condition, its
germinal centers as proven by markers such as CD10 and BCL-6. It is presentation in association with cholelithiasis has not been described yet.
renowned for BCL-2 overexpression which results from translocation t
(14; 18)/IGH-BCL2. Rarely, especially in high grade cases, one or more
immunomarkers might be lost, making accurate diagnosis difficult. We E-PS-10-008
present an unusual case of follicular lymphoma showing loss of BCL-2, Follicular dendritic cells sarcoma - two case reports
CD10, BCL-6 and negative MUM-1. S. Sotiriou1, A. Bouzakis2, I. Kostopoulos1, V. Tzioufa1, T. Koletsa3
1
Methods: Our patient is a 66-year-old female with resected colonic ade- Pathology Department, Faculty of Medicine, Aristotle University of
nocarcinoma (pT3N2b). Serial CT scans showed progressively enlarging Thessaloniki, Greece, 2 Histopathology Lab. Serres P, Greece,
3
lymph nodes despite adjuvant chemotherapy. Excisional biopsy was ob- Pathology Department, Medical School, Aristotle University of
tained and revealed multiple lymph nodes, some showing effaced archi- Thessaloniki, Thessaloniki, Greece
tecture, replaced by large follicles which are composed predominantly of
centroblasts with centrocytes. Extracapsular extension was also seen. Background & Objectives: Follicular dendritic cell sarcomas (FDCSs) are
Three lymph nodes showed extensive necrosis mostly due to previous rare neoplasms. The aim of these case reports is to raise awareness regarding
intervention. Immunohistochemical stains showed tumour cells were pos- this unusual entity and to point the importance of the differential diagnosis.
itive for CD20 and PAX-5. Methods: A 46-year-old man and a 38-year-old woman presented with
Results: However, BCL-2, CD10, BCL-6, CD30, CD15, CD3 and MUM-1 right and left cervical lymphadenopathy respectively. The clinical history
were all negative. CD23 highlighted attenuated dendritic meshwork. Ki67 and examination were otherwise unremarkable. Both have undergone a
was up to 40% and highlighted loss of zonation. Flow cytometry failed to diagnostic lymphadenectomy.
show neoplastic process. FISH using dual fusion probe for IGH/BCL-2 gene Results: Microscopically, the lymph nodes were almost entirely replaced
rearrangement was negative. Finally, PCR showed clonal immunoglobulin from a neoplastic population of ovoid to spindle cells with moderate
heavy chain and kappa light chain gene rearrangement. As a result, a diag- atypia. The nuclei were elongated or ovoid, occasionally exhibiting clear
nosis of follicular lymphoma grade 3a was made. Bone marrow biopsy changes or membrane folding. Giant cells with pleomorphic nuclei with
revealed minimal para-trabecular involvement. pseudoinclusions were observed in the second case. The neoplastic cells
Conclusion: In conclusion, unusual loss of expression in follicular lym- of both lesions showed similar immunophenotype: Vimentin+, CD21+,
phoma should not preclude accurate diagnosis. Such cases remind us that CD23+, Fascin+, HLA-DR+, S100+/-, CD68+/-, CD45-, AE1/AE3-,
the histomorphology is our cornerstone to make a diagnosis. MelanA-, HMB45-. Based on the histological and immunohistochemical
findings, our final diagnosis was that of FDCSs.
Conclusion: Depending on the location, FDCSs should be differentiated
E-PS-10-007 from other histological subtypes of dendritic cell tumours, but also from
Erdheim-Chester disease co-occurring with cholelithiasis associated primary or metastatic neoplasms. If FDCS is not considered in the differ-
Langerhans cell histiocytosis ential diagnosis, its positivity to nonspecific markers, such as CD68 and
S. Aviel-Ronen1, S. Fichman-Horn2, S. Zoabi3, R.D. Mazor4, G. Gitstein5 S100 protein can lead to misdiagnosis. Clinicopathological correlation
1
Department of Pathology, Sheba Medical Center, Tel-Hashomer, Israel, and immunohistochemical assays are of paramount importance in the
2
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, differential diagnosis.
 Virchows Arch

E-PS-10-009 CD34-. According the clinical data, histomorphology and

Bone marrow involvement in lymphoma: a histomorphologic and imunochistohemistry, final diagnosis was: Blastic plasmacytoid dendritic
immunophenotypic study cell neoplasm.
S. Sharma1, S. Yadav1, K. Rahman2, M. Murari1 Conclusion: It is very rare (< 100 cases reported), so the main problem is
1
Department of Pathology, SGPGIMS, Lucknow, India, 2 Department of to make a proper diagnosis. The proper diagnoses is very important today,
Clinical Haematology, SGPGIMS, Lucknow, India especially we are in the era of highly personalised therapy.

Background & Objectives: Bone Marrow (BM) evaluation has a key

role in workup of a case of lymphoma. BM involvement by lymphoma is E-PS-10-012
a definite evidence of disseminated disease and provides important infor- Breast implant-associated anaplastic large cell lymphoma with
mation for decisions regarding treatment. lymph node metastasis
The aim of the study was to analyse the prevalence of bone marrow L. Barona García1, G. Ruiz García1, M.I. Oviedo Ramírez1, A. Salazar
involvement and correlate histomorphologic findings with Nicolas1, M.I. Ortuño Moreno1, A. Caballero Illanes1, E. Martínez
flowcytometric analysis in a series of patients with lymphoma. Barba1
1
Methods: We retrospectively analysed 254 consecutive bone marrow Servicio de Anatomía Patológica, Hospital Clínico Universitario Virgen
(BM) biopsies which were performed for evaluation of lymphomatous de la Arrixaca, Spain
involvement over a period of 3 years. Bone marrow involvement was
assessed by conventional morphology, Immunohistochemistry and flow Background & Objectives: Breast implant-associated anaplastic large
cytometry (FC) in BM samples. Clinical, biochemical and hematological cell lymphoma (BI- ALCL) is an extremely rare form of non-Hodgkin's
findings were also reviewed. lymphoma. It’s a newly recognized provisional entity in the 2017 revision
Results: BM was involved in 160 (63%) cases. The distribution of some of the World Health Organization Classification of Tumours of
of the common lymphoma subtypes among BM positive cases was: CLL/ Hematopoietic and Lymphoid Tissues that usually occurs at a median
SLL (39.3%), MCL (13.7%), DLBCL (6.8%), Follicular lymphoma of 9 years after the implantation. In most cases, BI- ALCL is a localized
(6%), and Hairy cell leukemia (2.5%). Diffuse (55.6%), mixed nodu- disease and complete surgical resection of capsule and implants achieve
lar+interstitial (17.5%) and interstitial (11.2%) were more common pat- total remission of the disease.
terns of BM infiltration. Majority (68%) of cases had extensive (>50%) Methods: A 35-year-old woman with bilateral breast implant 8 years ago,
and only 10% cases had minimal lymphoid infiltration. There was a presented with right breast pain, swelling and enlargement and a palpable
significant correlation regarding percentage lymphomatous involvement mass in the right lower inner breast, and axillary and supraclavicular
between BM biopsy and FC (p<0.001). lymphadenopathy. The patient underwent bilateral capsulectomy and
Conclusion: Morphologic detection of lymphomatous involvement in prosthetic excision.
bone marrow trephine biopsy still remains the “gold standard” In lym- Results: Gross exam of the breast implant capsule showed a large tumour
phoma staging. The ancillary techniques like IHC and Flowcytometry are mass with extensive infiltration. Histology confirmed features of ALK-
important for sub-typing and identifying minimal involvement on negative BI-ALCL of T-cell phenotype. Furthermore, a 2,5 cm-round‐
histomorphology. shaped lymph node occupied by the same clusters of large‐sized and
pleomorphic cells with abundant cytoplasm and vesicular nuclei contain-
ing prominent nucleoli was found. Immunohistochemically, neoplastic
E-PS-10-011 cells were diffusely positive for CD30, CD5, CD43 and negatives for
Blastic plasmacytoid dendritic cell neoplasm ALK, CD20, PAX5, CD8, CD15, EMA y EBV-LPM.
J. Ilic Sabo1,2, T. Lakic1,2, M. Panjković1, A. Ilic1,2, Z. Vrekic2, Conclusion: To the best of our knowledge, only 16 cases of BI‐ALCL
D. Ćuk2 with axillary lymph node involvement have been reported in literature.
1
University of Novi Sad, Faculty of Medicine, Serbia, 2 Clinical Center We report a rare case of BI‐ALCL with agressive behaviour and lymph
of Vojvodina, Novi Sad, Center for Pathology and Histology, Serbia, node metastasis. The patient continues treatment with standard regimens
containing cyclophosphamide, doxorubicin, vincristine and prednisone
Background & Objectives: Blastic plasmacytoid dendritic cell neo- (CHOP) with poor response until now.
plasm was initially described in 1995 as acute agranular CD4-positive
natural killer (NK) cell leukemia. It is clinically aggressive tumour de-
rived from the precursors of plasmacytoid cells. It has a high frequency of E-PS-10-013
cutaneous and bone marrow involvement and leukemic dissemination. In An unusual case of a pure erythroblastic sarcoma diagnosed in a
2016 World Health Organization classification of tumours of the hema- patient with acute megakaryoblastic leukemia (AML M7)
topoietic and lymphoid tissues it has a current name- blastic plasmacytoid Z. Prouzova1,2, D. Mikulenkova3, R. Simeckova3, V. Campr4, R. Kodet4
1
dendritic cell neoplasm. Department of Pathology Third Faculty of Medicine, Charles
Methods: We got for the analysis the sample of neck lymph node, after a University and University Hospital Kralovske Vinohrady,
month sample of bone marrow biopsy, and after a year the biopsy of skin Czech Republic,
2
change. The analysis was performed with standard stains and additional Department of Pathology and Molecular Medicine Second Faculty
immunohistochemistry: CD56, CD123, CD4, CD68, CD43, CD33, of Medicine, Charles University and University Hospital Motol,
CD117, CD15, CD14, TdT, CD2, CD3, CD5, CD7, CD20, CD8, gran- Czech Republic, 3 Institute of Haematology and Blood Transfusion,
zyme B, BCL2, BCL6, MPO, CD34. Prague, Czech Republic, 4 Department of Pathology and Molecular
Results: Lymphadenomegalia colli appears at male 57 years old. In tre- Medicine Second Faculty of Medicine, Charles University and
phine biopsy the morphological finding was acute leukemia. In skin bi- University Hospital Motol, Czech Republic
opsy dermal infiltration (sparing of epiderm and adnexa) with medium
sized cells blastoid appearance, irregular nuclei and conspicuous nucleoli. Background & Objectives: A 62-year-old woman with a 2-year-history
Imunochistohemistry in tumour cells was: CD56+, CD123+, CD4+, of AML M7 (secondary to MDS-RCMD del(5q), which had been diag-
CD68+, CD43+, CD33+, CD117-/+, CD15+, CD14-/+, TdT-/+, CD2-, nosed 6 years before) with a poor therapeutic effectiveness and disease
CD3-, CD5-, CD7-, CD20-, CD8-, granzyme B-, BCL2+, BCL6-, MPO-, progression, was brought to our hospital for biopsy of a Th12 tumour
Virchows Arch

mass (clinically susp. sarcoma). At the time of the biopsy the patient was Methods: A 54-year-old man with no history presented with a complaint
seriously ill and developed severe pancytopenia and coagulopathy, which of respiratory difficulties. There were no palpable cervical lymph nodes
led to her death. The final diagnosis of the vertebral tumour was made a or B symptoms. Pathological examination found a cyst with the surround-
few days later. ing tissue replaced by a diffuse lymphoid proliferation of small lympho-
Methods: Tissue from the biopsy was formalin-fixed, sampled and then cytes with scant cytoplasm, round nucleus, clumped chromatine. The
routinely processed. Immunohistochemistry was performed using a broad immunophenotype showed leukaemic B cells CD20, CD5, CD23,
panel of myeloid and lymphoid markers. BCL2 and IgD and absence of CD10, cycline D1 and SOX11.
Results: The tumour was composed of large monomorphic blast cells Results: The retained diagnosis was tonsillar cyst associated with chronic
with basophilic cytoplasm and large round nuclei. lymphocytic leukaemia (CLL).
Immunophenotypically they were positive for CD71, glycophorin A, E- Conclusion: The pitfall of the case represents the diffuse replacement of
cadherin and weakly positive for CD45. Other markers (CK AE1/3, CD4, the normal lymphoid tissue and the basic knowledge in small cell lym-
CD5, CD15, CD20, CD30, CD34 CD56, CD61, CD117, CD138, phoid proliferations. The presence of persistent tonsillar cyst on elderly
HMB45, Melan A, MPX, MUM1, S100, TdT) were completely negative. patients should alert for the possibility of an indolent lymphoma. The
The morphology and immunohistochemical profile of the tumour was present case highlights the difficulty to recognize CLL in tonsillar cysts,
consistent with a diagnosis of erythroblastic sarcoma. and the diagnosis should be supported with immunohistochemistry.
Conclusion: An erythroblastic sarcoma in a pure form is a very unusual
variant of myeloid sarcoma and few cases have been reported, especially
in association with an underlying, and also rare, hematologic disease such E-PS-10-018
as was seen in this extraordinary case. Diffuse large B-cell lymphoma and prognostic significance of immu-
nohistochemical antibodies VEGF and COX2
Z. Nikin1, L. Popovic1,2, N. Solajic1, T. Ivkovic-Kapicl1, S. Knezevic-
E-PS-10-015 Usaj1, M. Panjkovic1
1
The leukemic cells frequently lose CD10 expression in Follicular University of Novi Sad, Faculty of Medicine, Serbia, 2 Institute for
Lymphoma with leukemic presentation Oncology of Vojvodina, Serbia
S. Chuang1
1
Chi-Mei Medical Center, Taiwan Background & Objectives: Diffuse large B-cell lymphoma (DLBCL)
is one of the most common lymphomas in the world and represents
Background & Objectives: Follicular lymphoma (FL) is a malignant B- up to 30% of all non-Hodgkin lymphomas. It is usually a primary
cell lymphoma of follicular center B-cell origin and frequently involves disease but also it can develop secondary as a result of the progres-
lymph nodes, but also spleen, bone marrow, and peripheral blood and sion of low-grade lymphomas. In most cases, the disease begins in
Waldeyer’s ring. The neoplastic cells of FL nearly always express germinal lymph nodes.
center B-cell antigens CD10 and bcl-6. FL with leukemic presentation (FL- Methods: Our research has included 92 patients who were diagnosed at
LP) is uncommon and has not been well characterised from Taiwan yet. the Institute for Oncology of Vojvodina from 2003 to 2011. They were
Methods: We retrospectively searched for cases of FL-LP in our institu- treated according to modern standard protocols including Rituximab. We
tion from January 2000 to October 2018. We characterised the leukemic have used immunohistochemical antibodies VEGF and COX2. Sex, age,
cells by flow cytometric immunophenotyping and biopsies by immuno- nodal/extranodal origin, and survival were found in medical files.
histochemistry and fluorescence in situ hybridization (FISH). Clinical Results: VEGF was positive in 27,7%, COX2 in 63,64%. Older patients
history was reviewed. had significantly less often COX2 expression. There was no significant
Results: We identified 13 (6.2%) of 212 cases of FL-LP, all de novo correlation between the expression of VEGF and age or between the
neoplasms. All cases had concurrent tumours: 12 (92%) low-grade and expression of VEGF and COX2 with sex neither with nodal/extranodal
one grade 3A. CD10 was expressed in the leukemic cells in 38% (5/13) origin. VEGF and COX2 as markers of signaling pathways for angiogen-
cases by flow cytometry and in 77% (10/13) cases in the tumour tissues esis and inflammation respectively did not have a significant correlation
(p= 0.0471, Chi-squared test). Reciprocal translocation of IGH/BCL2 was with worse prognosis.
identified in 85% (11/13) cases by FISH. The 2- and 5-year survival rates Conclusion: It seems that the use of antibodies VEGF and COX2 is not
were at 100% (7/7) and 83% (5/6), respectively. helpful for prognosis of patients with DLBCL. We should be rational and
Conclusion: In FL-LP, the lower CD10 expression rate of the leukemic use only basic antibodies for determination of immunohistochemical sub-
cells might be due to different epitopes used in flow cytometry as com- type and antibodies necessary for differential diagnosis.
pared to immunohistochemistry. Alternatively, loss of CD10 expression
might play a role in the pathogenesis of leukemic change. The low CD10
expression rate is a diagnostic challenge if only flow cytometric E-PS-10-019
immunophenotyping is used for diagnosis without biopsy. Experience with 84 cases of bone marrow amyloidosis - caution ad-
vised as deposits are frequently extramedullary and may be associ-
ated with non-AL amyloidosis
E-PS-10-016 M. Picken1
1
The surprise within the cyst Loyola University Medical Center, USA
I. Dumitru1, M.A. Bani1, A. Bourgogne1, N. Talhi1, X. Sastre1
1
CHI Créteil, France Background & Objectives: Progress in treatment of systemic amyloid-
oses has created the need for defining organ specific involvement. Thus
Background & Objectives: Tonsillar cysts are characterised by a squa- not only the presence but also the location and the extent of amyloid
mous epithelial lining with underlying follicular lymphoid tissue, resem- deposits in various organs has implications for diagnosis and therapy.
bling tonsillar crypts. Non-Hodgkin lymphoma of the tonsils accounts for The situation with bone marrow (BM) has not been addressed. We sought
less than 1 % of malignant head and neck tumours as a whole, and to evaluate the distribution of amyloid in 84 consecutive bone BM spec-
commonest histologic type is diffuse large B cell lymphoma. Tonsillar imens positive for amyloid and correlate it with clinical data.
involvement in chronic lymphocytic leukemia (CLL) is rare and has only Methods: Out of ∼ 800 BM biopsies evaluated with Congo red stain, in
been reported 7 times in the literature. We herein present another excep- 84 patients amyloid was detected. We evaluated the distribution of de-
tional case. posits and correlated with clinical data. The M:F ratio was 1.3:1 and the
 Virchows Arch

mean was 65 years (range 26-94). Plasma cell % ranged from 1-80%, Methods: A 72-year-old man with a history of high blood pressure pre-
mean 13.4%, median 8%. 29/84 (31%) patients had the first-time diag- sents with a palpable, but reducible abdominal mass in the umbilical
nosis of amyloidosis on BM biopsy 33/84 patients had >10% plasma cells region, that bulges at coughing. Abdominal CT revealed the presence of
of which 25 met the criteria for multiple myeloma. a mesenteric tumour. A solid mass, adherent to the ascending and trans-
Results: The location of amyloid deposits was variable and included verse colon, was found during the exploratory laparotomy. Surgical ex-
marrow stroma (19), vessel wall (26), periosteal soft tissue (POST, 19); cision of the tumour was performed. Representative slides of the resected
in 19 cases with slides no longer available for review, location of deposits specimen were examined using haematoxylin-eosin stain and several im-
could not be specified. While majority of patients had AL (light chain munohistochemical markers: CD20, CD3, CD5, bcl-6, bcl-2 and Ki-67.
amyloid), AA and ATTR were also diagnosed in 2 and 4 cases respec- Results: Macroscopic examination of the resected tissue showed a well
tively. Marrow stromal deposits were seen exclusively in AL while vas- demarcated, encapsulated, brown tumour, 6x4,5x4 cm in size.
cular and/or POST deposits were associated with AL, AA and ATTR. Histopathologic examination and immunohistochemical findings re-
Conclusion: There is significant heterogeneity of amyloid distribution in vealed a lymphoid proliferation with features compatible with
patients with AL with extramedullary/periosseous amyloid deposits being Castleman's disease, hyaline-vascular subtype.
more frequent than medullary. In non-AL deposits may be detected in Conclusion: This case represents the first unicentric Castleman's disease
BM specimens. These findings raise the need for development of a con- with mesenteric location reported in our department. In the presence of a
sensus definition of what constitutes marrow involvement in amyloidosis mesenteric mass, this rare disease should be considered a possible diagnosis.
in general and in AL in particular and how it should be reported.

E-PS-10-022
E-PS-10-020 ALK-positive Large B-cell Lymphoma (ALK-LBCL) - a diagnostic
An exceptional pathological pattern of T-lymphoblastic lymphoma challenge. Presentation of two cases misinterpreted as carcinoma and
I. Msakni1, H. Raoueh2,3, N. Mansouri1, F. Gargouri1, A. Saidi1, A. sarcoma
Bouziani1, B. Laabidi2,3 G. Rymkiewicz 1 , O. Stanowska 2 , A. Szumera-Ciećkiewicz 3 , A.
1
Pathology Department; Military Hospital for Instruction of Tunis, Borysiuk 1 , M. Wągrodzki 1 , B. Ziarkiewicz-Wróblewska 4,1 , M.
Tunisia, 2 Tunis El Manar University, Medicine School of Tunis, Prochorec-Sobieszek5
Tunisia, 3 Military Hospital of Tunis, Department of Pathology, Tunisia 1
Department of Pathology and Laboratory Diagnostics, Maria
Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland,
2
Background & Objectives: Lymphoblastic lymphoma (LBL) accounts Maria Sklodowska-Curie Institute - Oncology Center, Department of
for approximately 2% of all non-Hodgkin’slymphoma (NHL) and the Pathology and Laboratory Medicine, Poland, 3 Institute of Haematology
majority (90%) are T- lymphoblastic lymphoma (T-LBL). It commonly and Transfusion Medicine, Diagnostic Haematology Department,
involves the mediastinum (thymus), nodal or extranodal sites include Poland, 4 Faculty and Department of Pathology, Medical University of
skin, tonsils, and spleen. It is most frequent in adolescent males. The Warsaw, Warsaw, Poland, 5 Department of Pathology, The Maria
infiltration of the lymph node is often diffuse. exceptionally, a Skłodowska-Curie Memorial Cancer Center and Institute of Oncology,
pseudofollicular pattern is produced mimicking follicular lymphoma. str. Wawelska 15 B, 02-034 Warsaw, Poland
Our aim was to present a case report of a T-LBL with pseudofollicular
pattern. Background & Objectives: ALK-LBCL is a rare subtype of diffuse
Methods: We report a case of a 28-year-old man with multiple cervico- Large B-cell Lymphoma CD20-negative, occurring in young men.
thoracic lymph nodes.Seven lymph nodes measuring between 8 and Clinical manifestation is usually nodal. Diagnostic challenge for surgical
15 mm were received in the Departement of Pathology. pathologists include cohesive morphology with sinusoidal infiltration,
Results: lymph nodes showed complete architectural effacement. They EMA- and occasionally cytokeratin and CD56 positivity, weak or nega-
were infiltrated by lymphoid proliferation with multinodular pattern.The tive staining for CD45/LCA.
cells were of medium size with a high nuclear-cytoplasmic ratio and Hereby, we present two cases of aggressive ALK-LBCL, misinterpreted
inconspicuous nucleoli. Mitotic figures were rare (one mitosis / 10 initially, clinically and pathologically, as carcinoma and sarcoma.
HPF). There was no starrysky pattern, no tumornecrosis and no large Methods: Two 40-years old men presented with bulky tumour of few-
cells.Tumour cells were TdT, CD3, CD4 and CD10-positive. They were weeks duration. First was suspected to be poorly differentiated carcinoma
pancytokeratin, CK5-6, P40, EMA, CD20, CD30 and BCL6-negative. of salivary gland with destruction of a mandible and the second: sarcoma
we concluded a T-LBL with pseudofollicular pattern. of the axilla. Microscopic appearance included epithelioid cell infiltrate
Conclusion: Due to the rarity of T-LBL with pseudofollicular pattern, the with immunophenotype: EMA[+]/CK[-]/S100[-]/desmin[-]/CD45[-]/
diagnosis can be difficult presenting problems of differential diagnosis CD20[-]/CD3[-]. Surgical biopsy specimens were required to secure rep-
with follicular B-lymphoma or follicular variant of T-NOS lymphoma. resentative material for broad immunohistochemistry (IHC) panel.
The use of an adequate panel of antibodies including tdt especially in Additionally, flow cytometry (FCM) and molecular analysis of the mate-
young subjects is necessary to make the exact diagnosis. rial obtained by fine needle aspiration biopsy (FNAB) was performed.
Results: Both patients were finally diagnosed with nodal ALK-LBCL.
FNAB/FCM demonstrated expression of CD45/LCA and pan-B/T/mac-
E-PS-10-021 rophage- cell markers, not/faintly detected by IHC. IHC revealed expres-
Unicentric Castleman's disease with mesenteric location: case report sion of ALK protein, confirmed by FISH and cytogenetics as presentation
O. Vita1, M. Cornianu1,2, A. Gheju1, A. Văduva1, A. Jurescu1, I. Mihai1, of ALK gene rearrangement. Patients obtained chemotherapy according to
S. Tăban1,2, A. Dema1,2 modified GMALL protocol; both achieved complete regression.
1
Department of Pathology, "Victor Babeș" University of Medicine and Conclusion: We present cases of ambiguous CD45/LCA neoplasms by
Pharmacy, Timișoara, Romania, 2 Department of Pathology, Emergency IHC with epithelioid morphology interpreted as non-haematological ma-
County Hospital Timișoara, Romania lignancy by surgical pathologists. In young men with nodal involvement
of aggressive neoplasm, especially with morphological and IHC incon-
Background & Objectives: Unicentric Castleman’s disease is a nonma- sistency, ALK-positive lymphoma, which can be CD45[-/+dim]/CK[+],
lignant lymphoproliferative disorder that usually occurs in the mediasti- should be included in the differential diagnosis. FNAB/FCM show high
num, presenting as a solitary lymph node mass. The location of the dis- diagnostic accuracy and effectiveness for lymphomas with plasmablast
ease in the mesentery is rare. differentiation.
Virchows Arch

E-PS-10-023 Results:
Variation CD markers of B-cell lymphmas
Y. Gulyaeva1, T. Nabebina1, A. Kozubovskaya1 Table 1
1
National Cancer Centre, Belarus
Gender Age Specimen Diagnosis
Background & Objectives: Immunophenotyping of leukocyte sub-
populations by the flow cytometry uses for the differential diagno- 1.Female 68 Surgical MZL
sis of lymphoproliferative diseases, determining the stage and mon- 2.Male 70 Surgical FCL
itoring the residual tumour clone. From 2014 to 2018 we described
determination of B- lymphocytes markers of patients with the sus- 3. Male 75 Surgical DLBCL
picion of LPD. There were peripheral blood (PB), bone marrow 4.Female 67 Surgical DLBCL
(BM) and lymph nodes (LNs) of 874 patients. The gender distri- 5.Male 74 FNB MZL
bution was 58.8% of men and 41.2% of women. 6.Female 57 Surgical DLBCL
Methods: The MoAbs used for labeling in flow cytometry were
obtained from Beckman Coulter (BC, USA). The final diagnosis 7.Female 37 FNB DLBCL
was established after comparing the results of morphology, 8.Female 40 FNB T-ALL/LBL
immunophenotyping and FISH. The evaluation of 874 patients 9. Female 79 Surgical MZL
(360 females, 514 males) with mean age of 49±12.8 years
10.Male 63 FNB MZL
revealed.
Results: Of the patients, 615 (70.4%) had CLL/SLL, 59 (6.7%) had 11.Male 78 FNB DLBCL
MCL, 4.3% with follicular lymphomas (FL) and 126 (14.4%) had 12.Female 71 Surgical MZL
reactivation without malignant cells. There were low level inten- 13.Male 72 FNB Waldenstrom`s macroglobulinemia
sity or absent CD5 expression on the surface B-cells of 44.7%
SLL patients. All cases were examined by addition markers 14.Male 58 FNB IgG-4 sclerosing disease
CD200, CD180, bcl-1, bcl-2, bcl-6 to recognize CLL/SLL from 15.Female 80 Surgical DLBL
another lymphoma types. All cases with strong expression of
CD200 were CLL/SLL. Besides we had 2.1% cases of FL
(CD10+ CD23– ) with moderate expression CD5+ . This cases FNB=fine-needle biopsy, MZL=marginal zone lymphoma,
were examined with marker Bcl-6 and FISH analyses. FCL=follicular lymphoma, DLBCL=diffuse large B-cell lymphoma, T-
Conclusion: The variation expression CD markers in different ALL/LBL=T-lymphoblastic leukaemia/lymphoma
types of material even from one patient confirms to use all tools Conclusion: Kidney involvement by LD is often underdiagnosed and
for diagnosis. However, it is difficult to make a differential diag- frequently (shown by the relatively large number of surgical specimens in
nosis of CLL/SLL from MCL when immunophenotypic features our study) leads to unnecessary surgical treatment. Therefore, early diagno-
are not typical. The study of variability markers expression is a sis by fine-needle biopsy of all tumour-forming kidney lesions followed by
fundamental criteria for the diagnosis, the expression of atypical detailed morphological and immumohistochemical study is mandatory.
markers will improve diagnosis, understand molecular mecha-
nisms, and evaluate the prognosis of the disease
E-PS-10-025
Histopathologic characteristics of multiple myeloma-institutional ex-
E-PS-10-024 perience in Bosnia and Herzegovina
The kidney as initial presenting site of lymphoproliferative disorders. J. Redzepagic1, D. Udovicic-Gagula2, E. Delic3, D. Spirtovic3, T.
A 5-year study from a haematopathology referral centre Kukuljac2, N. Bilalovic3
A. Papanikolaou1, G. Kanellis1, E. Economaki1, E. Pouliou1, L. 1
Clinical Center University of Sarajevo, Bosnia and Herzegovina,
Marinos1 2
Department of Pathology, Clinical Center University of Sarajevo,
1
Haematopathology Department/Evangelismos General Hospital, Bosnia and Herzegovina, 3 Clinical Center University of Sarajevo/
Athens, Greece Clinical Pathology and Cytology, Bosnia and Herzegovina

Background & Objectives: Kidney involvement by a lymphoprolif- Background & Objectives: Multiple myeloma is a rare blood cancer of
erative disorder (LD) is a rare occurrence either as primary (less plasma cells. Data about multiple myeloma in Bosnia and Herzegovina
than 100 cases in the literature) or as a secondary (14% in au- are insufficient.
topsy cases diagnosed prior to death) site of presentation. Initial Methods: We searched medical records for multiple myeloma from years
presentation of a LD in the kidney is even rarer and frequently 2017-2018. Pathologic characteristics together with immunohistochemi-
leads to unnecessary surgical treatment. With the object of cal analysis and demographic characteristics were evaluated trough the
stressing out the importance of early preoperative diagnosis and medical records from our institution.
assessing the relative frequency of various LD in the kidney we Results: There were 46 new cases in 2017/2018. The average year was 65.
present 15 such cases studied in a 5-year period from 2014 to Men were slightly more affected by the disease (52.2%) than women
2018 (Table 1). (47.8%). In both sexes frequent bone marrow infiltration by neoplastic cells
Methods: All cases were studied with standard hematoxylin and eosin was more than 60% (52.2%). The common bone marrow pattern of infil-
stains and immunohistochemistry tration was diffuse (45.7%). The kappa clone was frequent (65.2%)
 Virchows Arch

followed by lambda clone (34.8%). Plasmablastic morphology of neoplas- E-PS-10-027

tic cells was less frequent (28.3%) and was associated with lower infiltra- Sclerosing angiomatoid nodular transformation of the spleen: a case
tion. The women were more affected by diffuse infiltration by clonal pop- report of a rare entity
ulation of plasma cells (63.3%). The CD138 and CD38 positive plasma C. Nicolae1, M. Chivu1, F. Andrei1, C. Iosif2, A. Curte1
1
cells were found in 93.5%, followed by CD56 positive cells in 41.3%, "Elias" Emergency University Hospital, Bucharest, Romania, 2 "Sfânta
CD20 positive in 21.7% and CD117 positive plasma cells in 4.3%. Maria" Clinical Hospital, Bucharest, Romania
Conclusion: In everyday practice a diagnosis of multiple myeloma is
possible in less than 30% of infiltration of plasma cells together with Background & Objectives: Sclerosing angiomatoid nodular transfor-
evaluation of clonal population by immunohistochemical methods. The mation (SANT) of the spleen is a recently described, rare, benign
evaluation of plasma cell morphology together with pattern of infiltration lesion with unknown etiology and female predominance. Most
and percentage of infiltration are among important factor contributing to cases are either identified incidentally on imaging, or present with
correct diagnosis. Knowing these characteristics can help and provide abdominal pain.
accurate diagnosis and predict the patient outcome and tailor treatment Methods: We report a case of sclerosing angiomatoid nodular transfor-
strategies. mation of the spleen found incidentally on imaging.
Results: A 62-year-old male patient, with history of surgically resected
bilateral renal cysts and hypertension, was admitted at ‘Elias’ Hospital
E-PS-10-026 with symptoms of acute cholecystitis. Computed tomography scan inci-
Evaluation of CYCLON as a predictive biomarker of anti CD20 dentally revealed a solitary, well-circumscribed, splenic mass with lobular
response in diffuse large B-Cell lymphoma borders. Both cholecystectomy and splenectomy were performed. The
A. Bouroumeau1, L. Bussot1, T. Bonnefoix2, M. Callanan3,4, R. Gressin1, spleen specimen measured 160/80/70mm and presented a solitary, sharp-
A. Emadali2, H. Sartelet5 ly demarcated, solid mass, measuring 60/50 mm. The cut surface showed
1
Grenoble Alpes University Hospital, France, 2 Institute for Advanced coalescing red-brown nodules within a dense, white, fibrous stroma,
Biosciences, France, 3 Plateforme de Gènètique des Cancers solides et des slightly firmer than the normal splenic parenchyma. Microscopically,
Hèmopathies malignes, CHU Dijon, France, 4 Unitè d'innovation en H&E stain revealed a multinodular proliferation composed of slit-like,
Gènètique et Epigènètique des cancers, CHU Dijon, France, 5 CHU de round, or irregularly shaped vascular spaces and channels of varying
Grenoble, France caliber, lined by plump endothelium, with interspersed ovoid and spindle
cells. There were numerous extravasated erythrocytes and the intervening
Background & Objectives: Diffuse Large B-Cell Lymphoma (DLBCL) stroma was brosclerotic, with scattered myobroblasts, plasma cells,
is a clinically heterogeneous tumour, currently treated, in first line, using siderophages, and inammatory cells. Mitotic figures, necrosis or signifi-
R-CHOP (Rituximab, an anti-CD20 immuno-chemotherapy regimen, cant nuclear atypia were not present. Immunohistochemistry was positive
Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine Sulfate, diffusely positive for CD34 in the vascular proliferation, and positive for
Prednisone). However, about 20 percent of patients will not primarily CD31 in small vessels, with Ki67 positive in 5-10 % of tumoral cells.
respond or relapse. In this context, CYCLON, a novel nuclear germline Conclusion: The H&E and immunohistochemical findings were characteristic
factor, overexpressed in aggressive B-Cell Lymphoma, has been recently of sclerosing angiomatoid nodular transformation of the spleen. This is a very
identified as involved in Rituximab resistance in vitro. rare, benign entity, with a good prognosis and no recurrence after splenectomy.
The aim of this study is to validate these results in a clinical setting.
Methods: A retrospective quantitative study was undertaken from 68
DLBCL, in University Hospital of Grenoble, France. Between 2011 E-PS-10-028
and 2018, all patients with a de novo DLBCL (excluding all transformed Hepatosplenic T-cell lymphoma - a case series
DLBCL), treated in first line by R-CHOP and having a formalin fixed F. Ultimescu1, C. Dobrea1,2,3, S. Badelita4, B. Ionescu4, A. Bardas4,
tumour sample were included. D. Coriu4,3
1
Using Tissue MicroArrays technique, an immunohistochemical analysis Oncoteam Diagnostic, Romania, 2 Fundeni Clinical Institute, Romania,
3
of CYCLON expression was performed. Its level was scored semi- Carol Davila University of Medicine and Pharmacy, Bucharest,
quantitatively (percentage of positive cells and intensity), then correlated Romania, 4 Center of Haematology and Bone Marrow Transplantation,
with clinical and biological data, previously collected for each patient. Fundeni Clinical Institute, Romania
Results: CYCLON was expressed in 55 of 68 DLBCL (81%), but with
two significant nuclear staining aspects: one homogeneous and the other, Background & Objectives: Hepatosplenic T-cell lymphoma (HSTCL) is
heterogeneous, with a dot-like positivity. The univariate survival analysis a rare and aggressive T-cell lymphoma, accounting for less than 1% of all
did not reveal any association between CYCLON staining intensity, or non-Hodgkin’s lymphoma. We report three cases of HSTCL over a three-
percentage of positive cells, with survival. But, very interestingly, the year period (2015–2018).
homogeneous versus dot-like expression of CYCLON was strongly as- Methods: Three young male patients (23, 23 and 24-years-old) were
sociated with relapse free survival (p=0.0185). Preliminary multivariate admitted to hospital with hepatosplenomegaly without lymphadenopa-
analysis also suggests an opposite role for CYCLON, depending on thies, anemia, thrombocytopenia and bleeding gums. All of them
DLBCL molecular subtypes. underwent bone marrow biopsy and, one of them, splenectomy.
Conclusion: Our preliminary data confirm CYCLON as a predictive Histopathological, immunohistochemical and flow cytometry analysis
biomarker in R-CHOP treated DLBCL. Consistently with in vitro were performed on each case.
conclusions, suggesting a role for CYCLON in chromatin regula- Results: The histopathological evaluation of the bone marrow biopsy
tion, this is CYCLON accumulation in nuclear sub-structures (dot- revealed increased cellularity by diffuse neoplastic infiltrate composed
like aspect), rather than its expression level, that is associated with of small/medium sized lymphoid cells with interstitial and sinusoidal
bad prognosis. Further investigations will be carried out to study the distribution. The splenectomy specimen showed neoplastic cells infiltrat-
functional significance of these foci. ing both splenic cords and sinuses. The neoplastic cells were CD3+,
Virchows Arch

CD7+ and CD20-, CD5-, CD4-, CD8-, Granzyme B-. Flow cytometry Methods: Twenty six cases of B-CLL were collected from 2011 to 2018.
revealed tumoral cells that expressed CD45++, CD3, CD2 but lacked The evolution of each patient had been determined. Were considered: low
expression of CD4, CD8, CD5. proliferation index = [0 - 10% [, intermediate [10 - 25%] and high> 25%.
Conclusion: The histopathological, immunophenotypic and flow cytom- Results: The average was 60 (24-82). Sex ratio was 2. Twenty per
etry findings supported the diagnosis of Hepatosplenic T-cell Lymphoma, cent of patients had a low Ki67, 58% had an intermediate ki67 and
with a poor outcome: two of the patients died within first year after 22% had a high ki67. The overall survival rate was 65%. Two
diagnosis while the other patient deceased within 26 months (after relapse patients of the weak Ki67 group, 11 of the intermediate group
following hapoidentical hematopoietic stem-cell transplantation). This and 4 of the high group had survived. Relapse was observed in 2
case series highlights the importance of considering Hepatosplenic T- low Ki67 patients and 3 high Ki67 patients. No relapse was noted
cell lymphoma as differential diagnosis in the clinical setting of pancyto- in the middle group. Transformation into high grade lymphoma was
penia with hepatosplenomegaly, allowing early recognition of these ag- noted in 3 cases of low Ki67, 5 cases of intermediate Ki67 and 3
gressive neoplasms. cases of high Ki67.
Conclusion: Our study reinforces the notion of B-CLL heterogeneity.
Prognostic value ofKi67 remains to be determined over larger series.
E-PS-10-029
HHV8 and EBV - associated lymphoproliferative disorders: a case
report of two rare entities in the same patient E-PS-10-031
J. Duarte Santos1, N. Lourenço-Silva2, V. Salvado3, M. Mafra1, J. Diffuse large B cell lymphoma located in the subcutaneous tissue
Cabeçadas4 Y. Dere1, S.Y. Celik2, O. Ilhan Celik3, V. Karakuş2, Î Dere3
1 1
Serviço de Anatomia Patológica, Centro Hospitalar Universitário de Mugla Sitki Kocman University, Faculty of Medicine, Department of
Lisboa Central, EPE, Lisboa, Portugal, 2 NOVA Medical School, Pathology, Turkey, 2 Mugla Sitki Kocman University, Faculty of
Lisboa, Portugal, 3 Serviço de Medicina 1.2, Centro Hospitalar Medicine, Department of Haematology, Turkey, 3 Mugla Sitki Kocman
Universitário de Lisboa Central, EPE, Lisboa, Portugal, 4 Serviço de University, Faculty of Medicine, Department of Surgery, Turkey
Anatomia Patológica, Instituto Português de Oncologia de Lisboa
Francisco Gentil, EPE, Lisboa, Portugal Background & Objectives: Diffuse large B cell lymphoma is the
neoplasm of large B lymphoid cells which generally presents with
Background & Objectives: Germinotropic lymphoproliferative disorder nodal disease. Extranodal involvement is rare but the most common
(GLPD) and extracavitary primary effusion lymphoma (PEL) are rare localizations are bone, testis, spleen, Waldeyer ring, salivary gland,
human herpesvirus 8 (HHV8) and Epstein‐Barr virus (EBV) - associated thyroid, liver, kidney and adrenal gland. We herein report a case of
lymphoproliferative disorders with very few cases described in the liter- large B cell lyphoma located in subcutaneous tissue of the forearm.
ature. To our knowledge this is the second case report of an HIV-negative Methods: A male patient aged as 71 years applied to our hospital with
patient who progressed from GLPD to an HHV8 and EBV-positive high- rapidly growing mass located on the medial of the right forearm near the
grade lymphoma. elbow. In the radiological examination a mass lesion in the subcutaneous
Methods: We present the case of an 86-year-old immunocompetent adipose tissue containing thin septa with approximately 81x31 mm in size
woman with a 1-month history of left cervical lymphadenopathy with was found at the distal medial level of the humerus with a preliminary
no other symptoms. A computed tomography scan showed extensive diagnosis of fibrosarcoma or liposarcoma. Histopathological diagnosis is
cervical, mediastinal and abdominal lymph node enlargement. recommended.
Excisional biopsy of a left cervical lymph node demonstrated overall Results: An incisional biopsy was performed and the microscopic exam-
preservation of architecture with neoplastic cells with plasmablastic mor- ination revealed the diffuse infiltration of large sized lymphocytes
phology replacing germinal centers. reaching the subcutaneous fat admixed with scattered small lymphocytes.
Results: Neoplastic cells were positive for HHV8, EBV, MUM1/IRF4, The neoplastic large cells were CD20 (+), LCA(+), bcl6(+), CD10 (-),
CD30 and EMA, without immunoglobulin light chain restriction and MUM 1 (-), Bcl2(+) immunohistochemically and Ki67 proliferation in-
negative for CD20, CD138, BCL-6 and CD10, consistent with a diagno- dex was 55-60%.
sis of HHV8+ GLPD (EBV‐positive). 2 months later she presented with Conclusion: Extranodal involvement of diffuse large B cell lym-
exuberant generalized lymphadenopathy, fatigue and peripheral edema phoma is rare but it is important, for especially clinicians, to keep
and was readmitted. Surgical excision of a left cervical mass revealed a in mind that it can be seen in even extreme localizations such as
diffuse lymphoid cell neoplasm infiltrating adipose tissue and skeletal subcutaneous tissue.
muscle, consisting of medium and large cells with plasmablastic mor-
phology, with one or more nucleoli, apoptotic bodies and necrosis. The
immunophenotype of the neoplastic cells overlapped with the previous E-PS-10-032
population. The patient showed a decline in her clinical condition and Two cases of splenic inflammatory pseudotumour-like dendritic cell
died two days after the surgery. sarcoma, an EBV related tumour
Conclusion: We report the case of an HIV-negative patient with GLPD C. Masaoutis1, D. Sampaziotis2, A. Choutri3, V. Pantelaion1, E. Patsea5,
who subsequently developed an extracavitary PEL, strongly suggesting L. Abou-Asabeh5, D. Rontogianni2
1
an association between these two conditions. Evaggelismos General Hospital of Athens, Greece, 2 Department of
Pathology, Evangelismos General Hospital, Athens, Greece, 3 Nicosia
General Hospital, Cyprus, 4 Metropolitan General Hospital of Athens,
E-PS-10-030 Greece
Prognostic value of Ki67 in chronic lymphocytic leukemia B
G. Sahraoui1, L. Charfi1, R. Doghri1, R. Sellami1, K. Mrad1, M. Driss1 Background & Objectives: A 66-year old woman with a history of
1
Institute Salah Azaiez, Tunisia breast cancer since 2015 presented with a solitary solid 4 cm splenic mass
since 2017. A 72-year old woman presented with a cystic 8 cm splenic
Background & Objectives: Chronic lymphocytic leukemia B (CLL-B) mass, grown by ~20% over the last 8 months.
is the most common lymphoid hemopathy of the elderly. It is Methods: Light microscopy, immunohistochemistry and in situ hy-
characterised by a heterogeneous evolution. Our aim was to study the bridization for Epstein-Barr virus (EBV)-encoded small RNAs
prognostic value of the proliferation index (Ki67) in B-CLL. (EBERs).
 Virchows Arch

1
Results: Both lesions were circumscribed, partly encapsulated and com- Department of Pathology, University Hospital of Patras, Greece,
2
posed of a mixed population of mature plasma cells, small T- and B- Department of Internal Medicine, University Hospital of Patras, Greece,
3
lymphocytes forming few secondary follicles, and bland spindle cells in Department of Pathology, Medical School, University of Patras, Greece
short fascicles or storiform formations. Immunophenotype: spindle cells
were diffusely SMA+, fascin+ and patchily CD35+, but CD21- and Background & Objectives: Inflammatory pseudotumor (IPT) is a
CD23-; there was minimal IgG4 production; no ALK was noted. In situ family of diseases with diverse etiologies and unclear definition.
hybridization highlighted EBERs in many inflammatory and spindle cells Some IPTs may fall into the spectrum of the IgG4-related diseases
alike. These findings are consistent with inflammatory pseudotumour- (IgG4-RD). Here-in, we report a rare case of a splenic IPT with
like follicular dendritic cell sarcoma. concomitant pleuritis, with clinicopathological features suggestive
Conclusion: This is a probably indolent tumour of the spleen and/or of IgG4-RD.
liver, rarely involving the gastrointestinal tract, with a strong female Methods: A 51-year-old man was admitted with fever, rigors and mal-
predilection. Despite a somewhat inconsistent terminology in the past aise. Abdominal CT-scan revealed splenomegaly and a hypodense splen-
literature, the latest WHO classification (2017) adopts the designa- ic mass. Splenectomy was performed, and the histopathologic diagnosis
tion “sarcoma” for all inflammatory pseudotumour-like lesions of the was IPT. After months he was readmitted with similar symptoms. Blood
spleen, liver and/or gastrointestinal tract with presence of EBV in tests revealed elevated IgG4 titers-1020mg/dl(8-140). CT-scan revealed
spindle cells -not only in inflammatory cells-, irrespective of a fol- an encapsulated pleural effusion. Open biopsy and surgical drainage were
licular dendritic cell (FDC) or a fibroblastic reticular cell (FRC) performed and revealed "fibrosing pleuritis". He was discharged home on
immunophenotype. prednisone.
Results: Grossly, the spleen presents a well-circumscribed, non-en-
capsulated, solitary, white-grayish, firm, parenchymal nodule.
E-PS-10-033 Microscopy demonstrates a fibroinflammatory lesion with
Comparison of the low Disulfiram concentrations with or without myofibroblasts and variable numbers of small lymphocytes, plasma
copper ions on apoptosis and pro-apoptotic gene expressions in my- cells, eosinophils and foamy macrophages, without atypia, mitoses,
eloma cell lines or necrosis. Stroma was fibrosclerotic and storiform with hemosid-
D. Hrckova Drozdkova1, J. Gursky2, Z. Kolar3, J. Minarik1,4, K. Smesny erin deposition, without obliterative phlebitis. Myofibroblasts were
Trtkova1,2 positive for SMA, MSA, Vimentin and negative for HHV-8, LMP-
1
Institute of Clinical and Molecular Pathology, Faculty of Medicine and 1, ALK, CD34. CD138 highlights abundant plasma cells. The
Dentistry, Palacký University, Czech Republic, 2 Institute of Molecular IgG4-positive plasma cell count was 104/hpf and the ratio of
and Translational Medicine, Palacky University Olomouc, IgG4-/IgG-positive plasma cells was 60%. Pleural biopsy demon-
Czech Republic, 3 Department of Clinical and Molecular Pathology, strated marked fibrous thickening of the parietal pleura and
Palacky University and University Hospital Olomouc, Czech Republic, lymphoplasmacytic infiltration with small lymphoid follicles The
4
University Hospital, Olomouc, Czech Republic ratio of IgG4-/IgG-positive plasma cells was 25%.
Conclusion: The present report indicates that splenic IPT with in-
Background & Objectives: Disulfiram is highly potent against various creased numbers of IgG4+ plasma cells, belongs to the spectrum of
types of tumours, including hematological malignancies. This agent is known organ specific IgG4-RD and may be associated with involvement
to bind the copper (Cu) in a cell to form the DSF-Cu complex that causes of other IgG4-related organs.
oxidative stress and induces apoptosis. The goal of our study was to detect
apoptosis in two RPMI8226 and U266 myeloma cell lines caused by using of
different DSF concentrations with or without added copper ions. There was E-PS-10-036
subsequently carried out a comparison of the measured apoptosis with the A case of extramedullary involvement of myeloma: skin
expression of cyclin dependent kinases CDKN2B, CDKN2A and CDKN1A. Y. Dere1, S.Y. Celik1, O. Ilhan Celik1, L. Tekin1
1
Methods: Myeloma cell lines were affected by various concentrations of Mugla Sitki Kocman University, Faculty of Medicine, Department of
DSF with and without Cu added. Cyclin dependent kinase inhibitor JNJ- Pathology, Turkey
7706621 and the histone deacetylase inhibitor - SAHA, were used as
control pro-apoptotic agents. The RNA was isolated from treated and Background & Objectives: Plasma cell myeloma is a bone marrow
untreated cells (DMSO) with followed by cDNA preparation. based multifocal plasma cell neoplasm associated with an M protein.
Expression of studied genes was quantified by RT-qPCR and the apopto- Extramedullary involvement is generally a manifestation of advanced
sis was detected by Flow cytometry analysis. disease. Herein we present a case of myeloma with extramedullary
Results: Used low Disulfiram concentrations without Cu ions show a involvement.
higher percentage of apoptotic cells in compare to higher DSF concen- Methods: Eighty-six-year-old male diagnosed as myeloma a year
trations. In the accordance with this finding were expressions of pro- ago applied to hospital with nodular lesions in her back for two
apoptotic genes in treated myeloma cells. weeks. On physical examination nodular eytematous lesions were
Conclusion: Obtained results indicate a supported effect of already pres- found on the back near the scapula. Ultrasonographically a subcu-
ent Cu ions content, which is commonly present in tumour cells. Our taneous nodular mass with 2 cm size accompanied with inflamma-
described event could play an important role in the apoptosis induction tory changes around was revealed. A punch biopsy was performed
in multiple myeloma disease. to the patient.
Student grant LF_2018_001 and LF_2019_004 of the Palacky University Results: Histopathological examination revealed a plasmacytic infiltra-
Olomouc and a grant NV18-03-0050 of the Ministry of Health of the tion with eccentrical nuclei in the subcutaneous tissue. The immunohis-
Czech Republic. tochemical study revealed diffuse infiltration of CD138(+) and lambda
(+), kappa(-) plasma cells similar with the patient’s bone marrow biopsy
which was diagnosed as myeloma.
E-PS-10-034 Conclusion: Multiple myleoma patients nay manifest with
IgG4-related inflammatory pseudotumour of the spleen associated extramedullary involvements in various organs such as skin. In patients
with pleuritis: a rare case report who admitted to the dermatology polyclinic with nodular masses diag-
D. Bantouna1, C. Davoulos2, D. Siagris2, M. Andreou2, I.M. Grypari1, V. nosed with myeloma, an extramedullary involvement of the disease
Zolota3 should be considered.
Virchows Arch

E-PS-10-039 spread (Stage IE) and the patient was managed conservatively with
Plasmablastic lymphoma: diagnostic difficulties, report of 5 cases follow-up only.
and review of the litterature Conclusion: Most of the lymphomas occurring in the uterus are due to
E. Ben Hadj Khalifa1, S. Mestiri2, Z. Nfikha1, D. Chiba4, T. Zahmoul3, O. secondary involvement by systemic lymphoma. Primary extranodal mar-
Belkacem4, D. Dao1, S. Hmissa1 ginal zone B cell lymphoma is extremely rare. These lymphomas are
1
Cytology and Pathology Department CHU Farhat Hached, Sousse- monotonous, nodular and often restricted to the endometrium. They usu-
Tunisia, 2 Pathology Department, Farhat Hached Hospital, Sousse, ally do not cause symptoms and are detected incidentally after hysterec-
Tunisia, 3 Cancer Registry of the Tunisian Center, Tunisia, 4 Pathology tomy performed for any other reason. They are associated with excellent
Department, Farhat Hached Hospital, Sousse, Tunisia prognosis without adjuvant therapy.

Background & Objectives: Plasmablastic lymphoma (PL) is a subtype

of diffuse large B cell lymphoma characterised histologically by the pres- E-PS-10-041
ence of plasmocytoid differentiation. It is an aggressive lymphoma ob- Paediatric nodal marginal zone lymphoma - a case report
served on a particular patients (immunocompromised and / or HIV pos- T. Terzic1, J. Lazic2, N. Tosic3
1
itive patients) with predominance of extra-nodal forms. It is also Institute of Pathology "Prof. Dr Djordje Joannovic", Faculty of
characterised by a chemo resistance responsible of a bad prognosis. The Medicine, University of Belgrade, Serbia, 2 University Children's
aim of this study is to present the clinical, pathological and immunohis- Hospital, Belgrade, Serbia, 3 Institute of Molecular Genetics and
tochemical characteristics of PL through a series of 5 cases. Genetic Engineering, University of Belgrade, Serbia
Methods: The data were extracted from the records of 5 patients whose
diagnosis of PL was made in the pathological anatomy and cytology Background & Objectives: Paediatric nodal marginal zone lymphoma
department of Farhat Hached hospital of Sousse between 2014 and 2018. (PNMZL) is a rare subtype of NMZL with characteristic clinical presen-
Results: The sample includes 4 men and one woman aged between 37 and tation, pathohistological and molecular features, therapy and prognosis.
63 years old. None of these subjects is known to be positive for HIV. The Results: A 15-year-old boy with no remarkable past history, presented with
tumour sites were the stomach, the right colon, the lung, the brain and the painless enlargement of left submandibular lymph node (LN) for three
axillary region. Microscopic examination showed malignant tumour prolif- months. Chest radiography and abdominal ultrasound revealed no
eration of large, non-cohesive cells with abundant eosinophilic cytoplasm hepatosplenomegaly and lymphadenopathy elsewhere. Blood count test
and atypical nuclei with a prominent nucleolus. The mitoses are numerous. was normal. Biochemistry showed elevated uric acid 499 umol/l, AST
First-line immunohistochemistry involved epithelial, neuroendocrine and 45U/l, ALT 98U/l, and sedimentation rate (65mm/h). The patient underwent
mesenchymal markers that returned negative in 3 out of 5 cases (gastric, biopsy of LN (47x37x20mm). The histopathological examination revealed
pulmonary and colonic). The tumour cells are negative for CD3 and CD20; partial architectural effacement: follicular hyperplasia and nodular B-cell in-
the CD79a and EMA are expressed in 3 cases. CD138 is intensely and filtration with features of progressive transformation of germinal centers
diffusely expressed in all 5 cases. MUM1 was requested on 2 occasions and (PTGC). A CD20 immunostain shows an abnormal expansion of the mar-
returned positive. Ki67 was high (≥80%). EBV virus was carried out in ginal zone with infiltration of interfollicular space. These B-cells were nega-
only one case using in situ hybridization and the result was positive. tive for CD5, CD23, EBV-LMP1, bcl-6, CD10, EMA, CD30, CD15, MUM-
Conclusion: PL is a rare and aggressive lymphoma which is associated 1, and positive for bcl-2 and IgD. CD21 immunostain showed an expanded
with immunodeficiency. The diagnosis is made by histopathological exam- follicular dendritic cell meshwork. It was concluded that LN likely represent
ination, immunophenotyping, and the detection of EBV in the tumour cells. reactive follicular hyperplasia with atypical marginal zone hyperplasia or
possible PNMZL, with recommendation of polymerase chain reaction
(PCR) analysis. Additional IGH PCR analysis demonstrated biclonal heavy
E-PS-10-040 chain gene rearrangement. These findings were consistent with PNMZL.
Primary endometrial marginal zone B-cell lymphoma: a case report Follow-up was recommended without any treatment. The patient has
O. Ton Eryilmaz1, R. Ucak1, A.A. Ozagari1, F. Kabukcuoglu1 remained disease free for 34 months since diagnosis.
1
University of Health Sciences Sisli Hamidiye Etfal Hospital, Conclusion: We presented a rare case of PNMZL with morphological
Department of Pathology, Turkey features of PTGC, but immunohistochemistry and additional PCR
clonality analysis were crucial for final diagnosis. This case represents a
Background & Objectives: Primary lymphoma of the female genital diagnostic challenge because of their rarity in the paediatric population.
tract is rare, accounting for approximately 2% of all extranodal lympho-
mas and less than 0.5% of the gynaecologic malignancies. Primary
extranodal marginal zone B-cell lymphoma of the endometrium is excep- E-PS-10-042
tionally rare and only 15 cases have been described in English literature. PD1 expression in diffuse large B-cell lymphoma: pilot study
Methods: We report a case of primary endometrial marginal zone B-cell V. Oparnica1, M. Ostojic1, M. Prvanovic2, N. Boricic2, T. Terzic2
1
lymphoma. Faculty of Medicine, University of Belgrade, Serbia, 2 Institute of
Results: A 75-year old woman presented with uterovaginal prolapse and Pathology "Prof. Dr Djordje Joannovic", Faculty of Medicine,
pelvic pain complaints. She underwent vaginal hysterectomy and pelvic University of Belgrade, Serbia
floor repair. On gross examination, the endometrium was irregular and a
white coloured thickening was observed. Microscopically, the endome- Background & Objectives: A great number of published papers depict
trium and superficial myometrium contained a nodular infiltrate of mo- the Hans algorithm as an excellent prognostic criterion in stratifying pa-
notonous, small-sized, monocytoid-like lymphocytes with scant clear cy- tients with diffuse large B-cell lymphoma, no other specified (DLBCL,
toplasm and round nuclei with fine chromatin. Immunohistochemically NOS) into groups with a good prognosis (germinal centre B-cell, GCB)
the lymphoid cells expressed CD20, CD43 and bcl-2. They were negative and a more aggressive one (non germinal centre, non-GCB). The aim of
for CD3, CD5, bcl-1, CD23, bcl-6, CD10.The plasma cells were mono- our pilot study was analysis of PD1 positive tumour infiltrating lympho-
clonal, showing lambda immunoglobulin light chain restriction. The pro- cytes (TIL) and its expression on the tumour cells of DLBCL, along with
liferation marker Ki67 was expressed in approximately 8-10% of the determining a difference in the expression profile between the GCB and
neoplastic cells. Routine laboratory tests (complete blood count, bio- non-GCB subtype.
chemical profile, lactate dehydogenase) were within normal limits. A Methods: A retrospective study enrolled 39 biopsies from patients diag-
staging computed tomography scan showed no evidence of extrauterine nosed as DLBCL, NOS. The PD1 positive TIL were counted on five
 Virchows Arch

high-power fields (×400) using Cell Image software, and their average methyltransferases, whose mutations and aberrant expression were found
value was calculated. PD1 expression on tumour cells was marked as in many types of cancer. Study showed that NSD2 worked downstream of
either positive (≥10% positive cells) or negative. EZH2 in prostate cancer tumorigenesis. While EZH2 has been shown to
Results: Out of the 39 DLBCL samples, 18 (46.2) were GCB and 21 play an important role in DLBCL the role of NSD2 in DLBCL has never
(53.6) non-GCB subtype. The median of the analysed values for the been explored. In this study we aim to explore the expression of EZH2
PD1+ TIL’s was 69. The number of PD1 positive TIL’s was significantly and NSD2 and their prognostic role in DLBCL.
different between the GCB (99.3±57.8/HPF) and non-GCB phenotypes Methods: We performed immunohistochemistry to study the expression
(54.9±28.0) (p=0,0125). PD1 tumour positivity is mostly present in the of EZH2 and NSD2 in a total of 105 cases of DLBCL and analysed their
non-GCB subtype (12/21; 57.1%) compared to the GCB (3/18; 16.7%), correlation with different clinicopathological features of these patients
and this difference was also statistically significant (p=0,0195). and their overall survival status.
Conclusion: Increased number of PD1+ TIL may imply better prognosis Results: We found that both NSD2 and EZH2 were highly expressed in
in patients with DLBCL, but PD1 expression on tumour cells was more DLBCL. Their expression is highly correlated with each other and with Ki67
frequent in aggressive DLBCL and may be considered as a potential level. There is an opposite correlation between NSD2 and BCL2 level.
therapeutic target. Patients with high NSD2 expression showed a slightly better prognosis.
Conclusion: It is the first study to show correlation of expression of
EZH2 and NSD2 in DLBCL. Further studies about their working mech-
E-PS-10-044 anism may help to clarify the role of NSD2 in DLBCL and its potential as
Indolent NK lymphoproliferative disorder: a case report a new drug target.
L. Vassallo1, N. Maschio2, L. Soligo2, S. Grillo3, E.S.G. d'Amore4, A.
Scapinello1 Supported by National Natural Science Foundation of China NO.
1
Anatomical Pathology Department, Castelfranco Veneto Hospital, 31260270, 81660037; Yunnan Provincial Key Laboratory of molecular
Veneto Oncology Institute - IOV, IRCC Padua, Italy, 2 Haematology pathology 2016.
Department, Castelfranco Veneto Hospital, ULSS2 Marca Trevigiana,
Italy, 3 Gastroenterology Department, Castelfranco Veneto Hospital,
Veneto Oncology Institute - IOV, IRCC Padua, Italy, 4 Department of E-PS-10-046
Pathological Anatomy, San Bortolo Hospital, Vicenza, Italy SOCS1 expression in B-cell lymphoma-derived cell lines
P. Kuerten1, S.E. Weissinger1, M. Zahn2, R. Marienfeld2, P. Moeller2
1 2
Background & Objectives: Indolent NK lymphoproliferative disorder Institute of Pathology, University Hospital Ulm, Ulm, Germany,
(LPDs) of the gastrointestinal (GI) tract represents an under-recognised University Hospital Ulm, Institute of Pathology, Germany
and recently described entity easily misdiagnosed as an aggressive dis-
ease. This group of rare pathologies has been designated by Takeuchi Background & Objectives: SOCS1 (Suppressor of Cytokine Signaling
et al. as lymphomatoid gastropathy and by Mansoor et al. as NK-cell 1) is a cytokine-inducible negative regulator of the JAK/STAT signaling
enteropathy. Very few cases have been documented so far. Herein we pathway. Due to its antiproliferative effect SOCS1 is considered to act as
describe a new case with duodenal localization and a follow-up of 3 years. tumour suppressor. It is known, that inactivating SOCS1 mutations may
Methods: A 56-year-old African female with long-standing dyspepsia lead to constitutive activation of the JAK/STAT pathway and subsequent-
underwent endoscopic examination that revealed erythematous areas with ly to proliferation and survival of various lymphoma entities. Scope of
superficial erosions in the second portion of the duodenum. Multiple this work was to investigate SOCS1 protein status and SOCS1 RNA
biopsies were performed. Histological study and Immunohistochemical expression in different, especially B-cell lymphoma-derived cell lines.
stains were performed and EBV-encoded RNA (EBER) was searched Methods: To assess SOCS1 protein status immunoblot experiments were
with the in situ hybridisation (ISH) technique. The rearrangement of T performed. SOCS1 RNA expression was analysed through semiquantita-
cell receptor (TCR) gamma/delta chains genes was analysed. tive real-time PCR. Protein and RNA extracts were obtained from a) HEK
Results: Histological examination of duodenal tissue revealed a focal and 293T cells previously transfected with gradually decreasing amounts of
dense atypical lymphoid infiltrate sometimes containing large eosinophil- wild-type SOCS1-DNA and b) cell lines that either express wild-type (wt)
ic granules. This was admixed with sparse eosinophils, histiocytes and SOCS1 (LCL ([lymphoblastoid], U-MM1b [multiple myeloma], HBL-1
plasma cells. The infiltrate was displacing the mucosal glands and [ABC-DLBCL], L540 [ns-HL]) or show SOCS1 mutations (Karpas1106
expanding the lamina propria, with extension to the submucosal layer. [PMBL], L428 [ns-HL], MedB1 [PMBL]). Karpas1106 cells served as
No necrosis, epitheliotropism or villous atrophy were seen. The neoplas- negative control due to biallelic SOCS1 deficiency of this cell line.
tic cells were positive for CD56, CD2 and cCD3, and negative for CD4, Results: Discrepancies between RNA and protein abundances occurred
CD5, CD8, CD20, CD30 and EBER ISH. Clonal TCR rearrangement in two cell lines: HBL-1 cells (ABC-DLBCL, wt) seem to express large
was absent. A diagnosis of NK cell enteropathy was given. No chemo- SOCS1 protein amounts and low corresponding SOCS1 RNA while the
therapy was done. After a follow-up period of three years no progression L540 cell line (ns-HL, wt) shows strong SOCS1 RNA expression but no
of diseases was documented. detectable SOCS1 protein band by immunoblot.
Conclusion: In this study we report a case of NK-cell enteropathy and we Conclusion: We found remarkable differences between SOCS1 RNA levels
emphasize the importance of recognising this pathology to avoid inap- and corresponding SOCS1 protein expression especially in HBL-1 and
propriate therapies and discuss the spectrum of differential diagnosis. L540 cells. To identify the responsible mechanisms further investigations
regarding RNA and protein degradation in these cell lines will be necessary.

E-PS-10-045
Clinicopathological study of EZH2 and NSD2 expression in DLBCL E-PS-10-047
Y. Li1, Y. Pan2 Myelodysplastic syndrome with translocation t(2;8)(p13;p22) and
1
Dali University, China, 2 The First Affiliated Hospital of Dali secondary progression to acute myeloid leukemia - first case report
University, China F. Ultimescu1, C. Dobrea1,2,3, A. Tatic4, V. Popov5, D. Vasilache2, C.
Jardan2, D. Coriu4,3
1
Background & Objectives: Diffuse large B cell lymphoma (DLBCL) is Oncoteam Diagnostic, Romania, 2 Fundeni Clinical Institute, Romania,
3
a heterogeneous disease with various genetic and epigenetic changes. Carol Davila University of Medicine and Pharmacy, Bucharest,
Both EZH2 and NSD2 (WHSC1/MMSET) are histone Romania, 4 Center of Haematology and Bone Marrow Transplantation,
Virchows Arch

5
Fundeni Clinical Institute, Romania, Colentina Clinical Hospital, Flow cytometry demonstrated activated lymphocytes (CD38) -61% and
Romania B lymphocytes (CD19)- 8%. There was no any suspicious infiltrate in
inner organs or other bone.
Background & Objectives: Chromosome abnormalities in acute myeloid Conclusion: Anaplastic large T cell lymphoma (ALCL) ALK negative of
leukemia (AML) and myelodysplastic syndromes (MDS) are among the most bone is extremely rare malignancy. Clinicians and pathologists should
valuable determinants of prognosis and treatment decisions. We report a case keep in mind that ALCL can present with extensive bone involvement
of MDS with t(2;8)(p13;p22) and secondary progression to AML. without nodal involvement.
Methods: A 50-year-old female presented with anemia and thrombocy-
topenia (without eosinophilia). She underwent bone marrow biopsy and
aspiration. Histopathological and flow cytometry analysis were per- E-PS-10-049
formed, along with cytogenetics and molecular biology assessments. Morphological and clinical characteristics of newly diagnosed prima-
Results: The bone marrow biopsy and aspirate at diagnosis were consis- ry myelofibrosis patients in Latvia
tent with trilinear MDS: multilineage dysplasia (dyserythopoiesis, ALIP+ A. Breiksa1, J. Nazarovs1,2, R. Kleina3
1
, dysplastic micro/megakaryocytes with separated lobes), with 5% blasts. P. Stradins Clinical University Hospital, Latvia, 2 Riga East Clinical
Cytogenetics at diagnosis and follow-up identified t(2;8) and monosomy University Hospital, Latvia, 3 Riga Stradins University, Latvia
20: 45,XX,t(2;8)(p13;p22),-20. Molecular biology disclosed negative
BCR-ABL p210 and JAK2. At 6-month follow-up bone marrow aspirate Background & Objectives: Primary myelofibrosis (PMF) is a rare
revealed blastic infiltration (56% myeloblasts), associated with myeloproliferative neoplasm, which is included at ORPHANET da-
myelodysplastic features: hipogranular, hypolobated granulocytes, neu- tabase. PM is diagnosed by bone marrow biopsies and clinical cor-
trophil pelgerization and pleomorphic megakaryocytes with hyperlobated relation. There is very little data available about epidemiology and
nuclei or micromegakaryocites. In addition, flow cytometry at follow-up morphological and clinical characteristics of this disease in the
showed a blastic population(35%), positive for CD45, CD34, CD117, European Union and no data about this disease in Latvia. The aim
CD33, enabling the diagnosis of AML(M1) post-MDS. The pacient is of our research was to determine newly diagnosed PM patients’ mor-
alive, has achived partial response to chemotherapy (10% residual blasts) phological and clinical data in Latvia.
and has been referred to HCST(hematopoietic stem-cell transplantation). Methods: This study is retrospective. We obtained all patients (n= 130)
Conclusion: As far as we know, t(2;8) has previously been reported in with PMF from 2010 to 2015 in Riga East Clinical University Hospital’s
myeloid/lymphoid neoplasms with FGFR1 rearrangement, Burkitt lym- haematology centre. Bone marrow biopsy data, such laboratory tests as
phoma, chronic lymphocytic leukemia and acute lymphoblastic leuke- red blood cells, white blood cells, platelets, haemoglobin (HGB) and
mia. To our knowledge, this is the first case report of MDS with visual diagnostic tests were analysed.
t(2;8)(p13;p22) and secondary AML (M1). Identification of additional Results: Men were 60 (46.2 %;), women – 70 (53.8%) of all cases. Mean
cases is needed to determine the prognostic significance and therapeutic age was 67.08 ± 10.09 years. Disease was diagnosed in fibrotic stage in
importance. 56.2% (n= 73) cases. Prefibrotic stage was observed in 43.8% (n= 57)
cases. Myelofibrosis grades were as follows: MF0 33, 8%, n= 44; MF1
17, 7%, n= 23; MF2 29, 2%; n= 38 and MF3 19, 2%; n= 25.
E-PS-10-048 Splenomegaly was confirmed with imaging studies in 111 cases.
Primary bone ALK-negative anaplastic T cell lymphoma Hepatomegaly was diagnosed in 26 cases.
T. Zablocka1,2,3, S. Isajevs1,2,3, J. Nazarovs4,5, A. Repnikovs2 Conclusion: Overall primary myelofibrosis patients’ morphological and
1
Riga East University Hospital, Pathology Centre, Latvia, 2 The Hospital clinical characteristics are similar to these data worldwide. The disease
of Traumatology and Orthopaedics, Latvia, 3 Department of Pathology, was diagnosed in the fibrotic stage in more than half patients. Clinical
University of Latvia, Latvia, 4 P. Stradins Clinical University Hospital, data showed such clinical signs as hepatosplenomegaly, anaemia, and
Latvia, 5 Riga East Clinical University Hospital, Latvia leucocytosis. This research is the first which analyses primary myelofi-
brosis in Latvian population.
Background & Objectives: Primary malignant lymphoma of bone is
rare, accounting for approximately 7% of all bone malignancies and 5%
of all extranodal lymphomas. E-PS-10-050
Methods: The case reported 58 years old patient. Patient underwent Anaplastic large cell lymphoma: clinical and pathological study
clinical examination (MRI) and the bone trepane biopsy and tumorous M. Manai1, R. Doghri2, G. Sahraoui1, K. Kacem3, K. Mrad2, M. Driss4,
mass curettage. The tissue samples were stained with haematoxylin-eosin L. Charfi2
1
and immunohistochemically. Institute Salah Azaiez, Tunisia, 2 Department of Pathology, Salah
Results: The 58 years old woman had pain in sacrum area; pain Azaiez Institute, Tunisia, 3 Service d'hèmatologie, Hôpital Aziza
radiated to the right leg, after CT and MR imagining was found Othmana, Tunisia, 4 Department of Pathology, Salah Azaïez Institute,
suspected osteolytic changes and pathological fracture of the sacrum Tunisia
bone. The bone biopsy and tumorous mass excochleation was per-
formed. Macroscopically tumour mass appeared yellowish, smooth Background & Objectives: Anaplastic large cell lymphomas (ALCL)
consistence with sizes 8x8x3 cm. Histopathological examination represent less than 5% of non-Hodgkin's lymphomas in adults and nearly
showed irregular appeared thickened bone trabecular with atypical 35% of paediatric non-Hodgkin's lymphomas. The WHO classification
diffuse infiltrate with scant basophilic cytoplasm, some cells were distinguishes two types; ALCL ALK + and ALCL ALK-. The aim was to
binucleated-Reed-Sternberg like forms, some focus of necrosis. study anatomoclinical and immunohistochemical profile of ALCL
Immunohistochemical examination demonstrated Reed-Sternberg through a Tunisian cohort and to identify prognostic factors.
like cells which were LCA positive, CD30 positive, vimentin posi- Methods: Retrospective study of cases of ALCL collected over a period
tive, CD99 positive, CD4 and CD5 positive, CD3 negative, CD8 of 22 years (1995-2017), classified according to the WHO classification
negative, CD79a negative, CD20 negative, CD138 negative, (2016).
CyclinD1 negative, CD117 negative, Kappa and lambda negative, Results: Our series included 52 ALCL: 34 ALK- and 18 ALK +. The
ALK negative and CKAE1/AE3 negative. Subpopulation represented median age was 45.4 years (ALK -) and 35 years (ALK +). 73% of ALCL
small shaped T lymphocytes, which were CD3 positive, some CD68 ALK + were in advanced Ann Arbor stage (III or IV) versus 83% of
positive histiocytes and multiple leukocytes. ALCL ALK. ALCL ALK + were of phenotype T in 43% versus 50%
 Virchows Arch

in ALCL ALK-. Overall survival was 56% at 5 years in the ALK + group lymphomas. Our aim was to report histopathological features of these
versus 28.4% at 5 years in the ALK- group. lymphomas.
The factors of poor prognosis in the ALK + group: age> 18 years (P = Methods: We collected cases of colo-rectal NHL between January 1999
0.039), PS score> 2 (P <0.001); in the ALK- group: PS score> 2 (0.022), and December 2018.
the presence of B symptoms (P = 0.024) and bone marrow involvement Results: Our series included 20 cases. The average age was 46 years (3-
(P = 0.043). 74). Sex ratio was 1.5. MALT lymphoma was identified in 6 cases,
In multivariate analysis, PS score was found to be the only significant followed by large cell lymphoma B (5 cases) and Burkitt lymphoma
independent prognosis factor in the ALK+ group. PS score and presence (5cases) and finally mantle cell lymphoma (4cases). The immunohisto-
of B symptoms were both found to be significant independent prognostic chemical study was performed in 14 cases. The panel included variously
factors impacting OS and EFS. the following antibodies: CD3, CD20, CD5, CD10, CD30, CyclineD1,
Conclusion: In our study, we highlighted the clinical, immunohistochem- Tdt, Bcl2, C-Myc, Ki67, Cytokeratin, with an average of 5 antibodies
ical and prognostic differences between ALK+ and ALK- ALCLs. tested/case. The colon was affected in 17 cases, of which 5 were cecal.
The rectum was affected in 3 cases. The involvement was multiple (lym-
phomatous polyposis) in 2 cases of mantle lymphoma. Rectal lymphomas
E-PS-10-051 were in all cases a large cell B-cell. All cases of cecal lymphoma were
Biological role of ID3 expression in diffuse large B cell lymphoma Burkitt lymphoma. This lymphoma was diagnosed in 4 cases (out of 5) in
(DLBCL) children (3-9 years).
M. Trujillo Coronado1, R. Manso Alonso2, L. Cereceda2, M. Boiza Conclusion: The favourite site of these lymphomas is the cecum. MALT
Sanchez2, Y. Castro3, M. Garcia-Cosio4, F. Camacho5, J.F. Garcia6, lymphoma is the most common histological type. Mantle lymphoma is
M.A. Piris Pinilla2, S.M. Rodriguez Pinilla2 less common but is more frequently diagnosed in the colorectal area than
1
Hospital Universitario Fundacion Alcorcon, Spain, 2 Hospital in other segments of the gastrointestinal tract.
Universitario Fundacion Jimenez Diaz, Spain, 3 Hospital Universitario
de Guadalajara, Spain, 4 Hospital Universitario Ramon y Cajal, Spain,
5
Hospital Universitario de Getafe, Spain, 6 Hospital MD Anderson E-PS-10-053
Cancer Center Madrid, Spain Fascin expression in classical Hodgkin lymphoma and anaplastic
large cell lymphoma
Background & Objectives: Inhibitor of DNA binding 3 (ID3) is a mem- N. Boujelbene1, M. Driss1, R. Doghri1, I. Abbes1, N. Ben Hamida1, D.
ber of the ID family of helix-loop-helix (HLH) proteins that inhibit other Kacem1, K. Mrad1, L. Charfi1
1
HLH proteins-like TCF3. It has been found mutated in Burkitt lympho- Department of Pathology, Salah Azaiez Institute, Tunisia
mas, in these subgroup ID3 point biallelic mutation has been related to
complete absence of its expression. Its role in DLBCL has not yet been Background & Objectives: Fascin is an actin-bundling protein that was
characterised in depth. involved in the formation of dendritic processes.
Methods: We have taken advantage of a well-characterised monoclonal We aimed to analyse fascin expression in classical Hodgkin lymphoma
antibody recognizing ID3 to analyse its expression pattern in a cohort of (CHL) and to determine its usefulness in discriminating CHL from ana-
58 DLBCL patients. Clinical features of all patients are known. FISH plastic large cell lymphoma (ALCL).
studies of BCL2, BCL6, MYC genes as well as mutational analysis of Methods: Formalin-fixed, paraffin-embedded tissue samples from cases
this cases have been done. Statistical studies have been performed using of CHL and ALCL were analysed. Fascin expression was compared
SPSS programme. across each type of lymphoma with additional correlation between fascin
Results: The series consisted of 31 women and 27 men. Median age at positivity and the others antibody expression including CD3, CD20,
diagnosis was 62,5. 35 and 23 patients had a low-IPI and high-IPI score, CD30, CD15 and ALK.
respectively. All patients received R-CHOP, 37 (64%) achieved complete Results: A total of 18 archival cases of CHL (n=15) and ALCL (n=3)
remission. The median overall survival was 49 months (0-196), with 13 from adults and children were studied.
deaths from disease-related-causes. The mean age were 35 years (with extremes of 3 to 78 years old). The sites
ID3 was positive in 35 cases while complete absence of expression of involvement included 13 lymph nodes (11 cervical, 1 axillary and 1
was found in 17 cases (30%). Hans’s algorithm subclassified cases inguinal), 1 central (mediastinum) location, 2 hepatic biopsy and 2 Bone
into 22 germinal-center B-cell (GC) and 22 Activated-B-cell (ABC)- morrow. All 15 cases of CHL demonstrated intense positive staining for
phenotype. Loss of ID3 was directly associated with CD10 expres- fascin in the Reed-Sternberg cells including CD15 negative cases. Focal
sion, absence of MUM1 and GC phenotype. Negative ID3 expres- and moderate positivity for fascin was observed in one case of ALCL
sion was also related to better outcome (p=0.043) (2 dead patients in (33%) that does not express ALK. Fascin expression was correlated signif-
ID3- vs 14 in ID3+). icantly to the absence of CD3, CD20 and CD15 expression (p<0.0001).
Conclusion: ID3 negative identifies a better prognosis subgroup of Conclusion: Fascin is expressed consistently in Reed-Sternberg cells of
DLBCL-GC phenotype. CHL. It is a very sensitive marker particularly useful when CD15 is
Validation of this study and correlation with mutational events will be negative. Taking into the consideration that some CHL may even express
shown. cytotoxic molecules, differential diagnosis between CHL and ALCL may
be challenging. Fascin negativity or weak expression may help the exclu-
sion of CHL.
E-PS-10-052
Primary non-Hodgkin's lymphoma on the colon and rectum
M. Manai1, G. Sahraoui1, R. Doghri2, R. Sallami1, K. Mrad2, M. Driss2, E-PS-10-054
L. Charfi3 Significance of double expressor lymphomas and association with
1
Institute Salah Azaiez, Tunisia, 2 Department of Pathology, Salah DNA repair proteins
Azaiez Institute, Tunisia S. Bozkurt1, H. Toper2, T. Elibol3, T. Tuglular3
1
Marmara University Medical Faculty Pathology Department, Turkey,
2
Background & Objectives: Primary non-Hodgkin's lymphoma (NHL) Dokuzeylul University Graduate School of Health Science Molecular
of the colon and rectum is rare representing only 0.5% of all colorectal Pathology, Turkey, 3 Marmara University Medical Faculty Haematology
cancers. Colorectal localization constitutes 15 to 20% of all digestive Department, Turkey
Virchows Arch

Background & Objectives:The cases of diffuse large B-cell lymphoma, E-PS-10-056

NOS (DLBCL, NOS) which immunohistochemically exhibit MYC and Sclerosing angiomatoid nodular transformation of the spleen: 3 cases
BCL2 expressions are defined as double-expressor lymphomas (DEL). with different morphology
Several studies demonstrated DELs associated with adverse prognosis. In A. Cakir1, E. Calis1, O. Canoz2
1
our study, we aim to detect prognostic role of double-expressor subgroup Istanbul Medipol University, Department of Pathology, Turkey,
2
and association with DNA repair proteins. Erciyes University, Department of Pathology, Turkey
Methods: In this study, 90 cases of DLBCL, NOS diagnosed between the
dates of 2007 and 2015 have been evaluated retrospectively. Clinical and Background & Objectives: Sclerosing angiomatoid nodular transforma-
demographical data including age, sex, localization of tumour, Ann Arbor tion of the spleen (SANT) is a benign and rare vasculary lesion of the
stage and NCCN-IPI scores belonging to patients were collected and spleen with an unknown etiology.
immunohistochemical evaluations as well as overall survival analyses Here, we want to present 3 cases of SANT lesions, one with classic
have been carried out. Myc and Bcl2 protein expressions were analysed morphology and the others are in the spectrum of SANT.
to determine double-expresor lymphoma group. Additionally, expres- Methods: All patients were females and had one mass in the spleen.
sions of p53, base excision repair proteins (AID, UNG) and mismatch Case 1 was 46 years-old and had a history of breast carcinoma.
repair proteins (MLH1, MSH2, MSH6, PMS2) were also assessed. Splenectomy was performed with a pre-diagnosis of metastasis.
Results: Median age of the cases was 59, and male/female ratio was 0.95. Case 2 was 33 years-old with thrombocytopenia and splenectomy
Eleven cases (12.2%) which exhibited ≥40% Myc and ≥50% Bcl2 was performed for the 11 cm mass with a pre-diagnosis of SANT.
immunexpressions were classified as double-expressor DLBCL. Age Case 3 is 71 years old and the pre-diagnosis for the spleen mass was
greater than 60, advanced Ann Arbor stage, high NCCN-IPI scores, hamartoma or angiosarcoma.
≥40% MYC immunexpression and high Ki-67 proliferation index were Results: All of the masses had macroscopically demarcated red-
all associated with lower overall survival. Although a trend of lower brown lesions from the surrounding spleen; microscopically and
overall survival was observed in the double-expressor lymphoma group, immunohistochemically, 3 vessel types can be identified (CD34+,
this was not proven to be statistically significant. Also, no significant CD31+, CD8- capillaries, CD34-, CD31+, CD8+ sinusoids and
relation between AID, UNG and P53 immunexpressions with double- CD34-, CD31+, CD8- small veins). Case 1 had a classical
expressor lymphoma and overall survival could be detected. It is observed SANT lesion with macroscopic santral sclerosis of 4x3 cm mass;
solely correlation between immunexpressions of P53 and Myc. The loss microscopically slit-like, round or irregular shaped vascular spaces
of expression for MLH1, MSH2, MSH6, PMS2 antibodies are not de- lined by plump endothelial cells forming micronodules. In case 2,
tected in any tumour. no sclerosis can be identified macroscopically and microscopically
Conclusion: Our study showed that the prognostic value of DEL may not for the 11x10 cm lesion. Case 3 had a 7x5 cm lesion with focal
be reliable, so that further studies are needed to confirm. Also, our find- sclerosis macroscopically. Interestingly, this case had some
ings demonstrate that DNA mismatch repair protein loss in DBBHL is not degenerative/ancient changes, with pleomorphic nucleous in the
usual and it does not seem to have major role in lymphomagenesis. stroma. No IgG4 increase can be shown immunohistochemically,
all of the cases.
Conclusion: Case 1 was a classic SANT case. Although no detailed
E-PS-10-055 information can be found in the literature, we concluded that no/
Histiocytic sarcoma: a case report of skin involvement minimal fibrosis can be found in some, probably early SANT lesions
D. Gigliano1, M. Afonso1 and some degenerative changes can also be seen. Splenectomy is cure
1
IPO-Porto, Portugal for SANT.

Background & Objectives: Histiocytic Sarcoma (HS) is a rare malig-

nant hematologic neoplasm, accounting for less than 1% of all E-PS-10-057
hematolymphoid neoplasms. The etiology is unknown, shows no age or Intratumoral immune and stromal heterogeneity in follicular lym-
sex predilection, and is clinically aggressive. It consists of a diffuse pro- phoma: an implication in relapses and responses to
liferation of cells exhibiting the morphology and immunophenotype of immunotherapies?
differentiated histiocytes. We aimed to raise awareness to such a rare C. Lamaison1, F. Mourcin1, K. Tarte1
1
entity. UMR_S 1236, Universitè de Rennes 1, INSERM, Etablissement
Methods: We report a case of a 51-year-old woman with unremarkable Français du Sang, Rennes, France
medical history, referred to our Institution because of a rapidly growing
erythematous nodule of the right leg. The MRI scan revealed a 3.5x3.3cm Background & Objectives: Follicular Lymphoma (FL) B cells are
subcutaneous heterogeneous lesion. An initial incisional biopsy followed strongly dependent on a GC-like microenvironment including immune
by complete excision of the nodule was performed. and stromal cells. FL-B cells display different cytological grades, prolif-
Results: Microscopically, the neoplasm consisted of sheets of large cells eration rates, phenotypes, and subclonal genetic profiles depending on
with pleomorphic nuclei, prominent nucleoli and abundant eosinophilic their localization (LN versus BM), suggesting that trafficking within var-
cytoplasm. The lesion was centered in the dermis, ulcerated the overlying ious microenvironments could differentially impact FL pathogenesis and
epidermis and infiltrated the subcutis. Up to 6 mitoses per 10 high-power clonal selection. The characterization of specific niches supporting FL B
fields were encountered. Immunohistochemistry showed diffuse positiv- cells proliferation or FL ancestral common precursor clone (responsible
ity for CD68 and CD4, focal positivity for lysozyme and CD31, while for relapse and transformation) remains to be explored. Our objective is to
epithelial, melanocytic, lymphocytic, dendritic-cell and Langerhans-cell identify if different tumour-supportive niches exist that could in turn
markers were negative. These findings allowed a diagnosis of HS. support different subclonal evolution and affect responses to
Conclusion: HS is an exceedingly rare hematologic neoplasm, with a immunotherapies.
very aggressive clinical behavior. Therefore, a correct diagnosis is crucial Methods: We made use of in situ approaches by using multiplex IHF, and
for an adequate treatment. In spite of its reproducible morphology, the CLARITY clearing , and functional studies with a 3D co-culture model.
diagnosis of HS requires an extensive panel of immunohistochemical Results: We assessed the heterogeneity of stromal and immune cells and
markers for the exclusion of more common malignancies. The patient is identified two different niches in FL-LN. The first one, with a high FL-B
currently scheduled for re-excision due to inadequate margins and adju- cells proliferation, shows high expression of Cancer Associated
vant chemoradiotherapy. Fibroblasts markers (SPARC, periostin and podoplanin) that are
 Virchows Arch

correlated with i) a low number of cytotoxic cells ii) an increase of fol- Results: The surface of the mucosa was partially ulcerated and covered
licular helper T cells and macrophages iii) an anarchic vascularization. In by an irregular acanthotic epithelium. The general architecture of the
the second niche, FL-B cells are less proliferative, stromal cells express glands was preserved within pronounced and extensive squamous meta-
others markers like Madcam with high expression of CCL21, and few plasia of the salivary gland ducts and acini. In some instances, there was a
immune cells. pseudo infiltrative pattern and light surrounding inflammation. Some
Conclusion: We identified two niches within FL-LN, composed by im- ducts were dilated within mucous or necrotic debris.
mune and stromal cells with different phenotypes and functions. These Immunohistochemistry pointed flattened basal cells at the periphery of
data suggest a different capacity to support B-cells subclones which could epithelial islands. P53 was negative.
be related to drugs resistance. Conclusion: NS is a benign condition that usually involves salivary
glands of the oral cavity and upper aerodigestive tract. NS can mimic
malignancy, being confused with squamous cell carcinoma or
Sunday, 8 September 2019 – Wednesday, 11 September 2019 mucoepidermoid carcinoma. Well-characterised morphological features
E-PS-11 | Head and Neck Pathology and IHC expression of basal cell markers are helpful in differential diag-
nostic, mainly when material is limited.
E-PS-11-001
Hybrid carcinoma of the salivary glands: report of two extremely
E-PS-11-004
rare cases
An exceptional case of clear cell oncocytoma of palatine minor sali-
K. Kusafuka1, S. Miyabe2, K. Ishibashi2, T. Nakajima1, T. Sugino1
1 vary gland
Shizuoka Cancer Center, Japan, 2 Aichi-Gakuin University, Japan
S. Tzorakoleftheraki1, M. Givannakis2, S. Triaridis2, G. Tsiropoulos3, T.
Koletsa4
Background & Objectives:Hybrid carcinoma (HC) is defined as two or 1
Pathology Department, Faculty of Medicine, Aristotle University of
more distinct and separable carcinomas in the same topographic area and
Thessaloniki, Greece, 2 A' Otorhinolaryngology Department AUTH,
producing a single tumour mass. HC is extremely rare in the salivary
AHEPA Hospital, Greece, 3 Medical Department, AUTH, Greece,
glands. We report two additional case of HC. 4
Pathology Department, Medical School, Aristotle University of
Methods: We selected two HC cases from our pathology file during 2002-2018,
Thessaloniki, Thessaloniki, Greece
and examined them, clinically, histologically and immunohistochemically.
Results: Case 1 was an 87-year-old Japanese male. Salivary duct carci-
Background & Objectives: Clear cell oncocytoma (CCO) constitutes a
noma (SDC) was observed in the most area, whereas squamous cell
rare subtype of oncocytoma, characterised clinically by major salivary
carcinoma (SqCC) was seen in part. The former was positive for AR,
gland involvement and histologically by replacement of oncocytes with
GCDFP-15 and EGFR. Case 1 consisted of SDC and SqCC. Case 2 was a
clear cells. Cases of CCOs located at minor salivary glands have not been
70-year-old Japanese female. SqCC was seen, whereas large cell neuro-
reported. Herein we present an exceptional case of CCO arising in pala-
endocrine carcinoma (LCNEC), which were positive for NCAM and
tine minor salivary gland.
synaptophysin, was observed in the central area of this tumour. Case 2
Methods: A 44-year-old female proceeded to the hospital due to a left-
consisted of SqCC and LCNEC.
sided, painless palatine swelling. After clinical examination, imaging and
Conclusion: HC is an extremely rare entity. Although the combi-
Fine Needle Aspiration Biopsy, which showed findings consistent with
nation of SDC and adenoid cystic carcinoma or epithelial-
benign mixed tumour, she underwent surgical excision of the tumour. The
myoepithelial carcinoma has been reported, only three cases of
surgical specimen regarded a nodular, grayish-white, solid tumour, mea-
combination between SDC and SqCC has been reported.
suring 1,9 cm.
Moreover, case 2, which was composed of SqCC and LCNEC, is
Results: Histologic examination showed a circumscribed, encapsulated
the first case. In the diagnosis of HC, carcinoma with high-grade
neoplasm, consisted of oncocytes and clear cells, which were arranged
transformation should be ruled out.
into nests and surrounded by basal cells. Occasionally, characteristic tran-
sition from oncocytes to clear cells was evident. Phosphotungstic Acid-
Hematoxylin revealed oncocytic granular positivity. Both oncocytes and
E-PS-11-002
clear cells were immunoreactive to CK8/18, CEA and alpha-1-
Necrotising sialometaplasia of the larynx: a case report and review of
antichymotrypsin antibodies and negative to CD10, GFAP, S100, p63.
the literature
The latter immunostain highlighted the basal cells. The specimen includ-
M. Garcia Martos1, C. Perna Monroy2, R. Carrillo GIjon3, C. Prada
ed fragments of minor salivary gland. The diagnosis of CCO was set.
Puentes3
1 Conclusion: The majority of head and neck neoplasms may potentially
11312, Spain, 2 Univ. Hosp. Ramon y Cajal, Spain, 3 Univ Hosp
show clear cell change, causing diagnostic issues. CCO can affect minor
Torrejon, Spain
salivary glands and total excision of the lesion is the mainstay of therapy.
Since most mimickers of CCO are malignant neoplasms with adverse
Background & Objectives: Necrotizing sialometaplasia (NS) is a
prognosis, thorough morphologic, histochemical and immunohistochem-
benign condition that usually involves major and minor salivary
ical examination are crucial for making a safe diagnosis.
glands of the oral cavity and the upper aerodigestive tract. Only
four cases of NS of the larynx has been reported. The importance
of NS lies in its potential for clinical and pathologic confusion
E-PS-11-005
with either squamous cell carcinoma or mucoepidermoid carcino-
Primitive pure signet-ring cell intestinal type adenocarcinoma of the
ma. The pathogenesis is unknown but may occur in response to a
sino-nasal tract: an extremely rare entity
variety insults include previous biopsy, ischemia, surgery or
R. Cepurnaite1, E. Guadagno1, M. Fuggi1, S. Pigniatiello1, L. Insabato1
radiotherapy 1
Department of Advanced Biomedical Science of the University of
Methods: A 59-year-old male with dysphonia, without dyspnea and
''Federico II'' in Naples, Italy
throat pain. On the fiberoptic exploration, he presented an
arytenoepiglottic fold thickening with a light impairment of the motility
Background & Objectives: Sino-nasal adenocarcinomas (SNACs) are
of the right hemilarynx. CT scan revealed a mass in this region. Multiple
rare and clinically aggressive tumours. They are broadly categorized into
biopsies did not revealed malignancy.
the intestinal- and non-intestinal type.
Virchows Arch

1 2
A pure signet-ring cell carcinoma is an extremely rare subtype of the Tzaneio General Hospital of Piraeus, Greece, General Hospital of
intestinal-type adenocarcinomas. To our knowledge only 5 cases have Korinthos Greece
been reported in the literature. Our aim is to present a case of primitive
pure signet-ring cell intestinal type-adenocarcinoma of the sino-nasal tract Background & Objectives: Inflammatory myofibroblastic tumour is
with immunohistochemical profile and compare it with other cases re- a term that refers to a bening neoplastic disorder of unknown etiol-
ported in the literature. ogy that can appear in various locations, mainly affecting the lung.
Methods: A 75-year old male, ex-carpenter, with a history of nasal It affects individuals of both sexes and of a wide range of ages. It
obstruction and diplopia for 3 months had his biopsy taken at our can sometimes mimick other malignant entities under the clinic and
hospital in 2019. It showed an inflammatory polyp with some pathologic viewpoint. Our aim is to report one case of inflammatory
atypical reactive cells. Due to a high suspicion of malignancy, myofibroblastic tumour located in the parotid gland.
the patient underwent MRI following a total excision of the lesion. Methods: A 73-year-old male presented with a palpable right parotid
The tumour measured 8x3,5 cm. Microscopically, it was purely mass. Computed tomography revealed a tumour-like lesion measuring
composed of signet-ring cells floating in pools of extracellular 4,5 cm. in diameter. The lesion was surgically removed. Gross examina-
mucin. Foci of bone infiltration were observed. tion revealed a firm, yellowish tumour.
Results: The immunohistochemical study revealed a strong expression of Results: Microscopic examination revealed a benign neoplastic pro-
CK7, CK20, CDX2 and MUC2. An increased proliferative activity (Ki67 liferation of spindle cells with histological characteristics of
expression) using MIB-1 antibody was observed. Total body CT scan did myofibroblasts, in a highly vascular stroma comprising mainly of
not reveal any other lesion. All these results led to the diagnosis of pri- chronic inflammatory cells, such as plasma cells, lymphocytes and
mary pure signet-ring cell of intestinal type adenocarcinoma. The immu- histiocytes. No nuclear atypia or mitotic figures were present. In
nohistochemical evaluation of mismatch repair proteins revealed a micro- peripheral and a few central sites, residual parotid parenchyma and
satellite stability state (MSS). ALK protein and chromogranin were a microscopic growth of Warthin tumour were detected.
negative. Immunohistochemical analysis was positive for SMA, vimentin,
Conclusion: Pure signet-ring cell SNACs are rare and aggressive tumours. HHF35 and desmin and negative for pankeratin,
Their intestinal differentiation can be displayed by immunohistochemis- EMA,S100,ALK,CD34,CD23,CD21 and LCA.
try (positive staining for CK20 and CDX-2). To exclude the possibility of Conclusion: Parotid gland inflammatory myofibroblastic tumour is
these lesions being metastatic, careful digestive endoscopical examina- a very rare lesion which along with its nonspecific clinical ap-
tion is recommended. pearance may pose diagnostic difficulties. The differential diagno-
These tumours show specific clinical, macroscopical and histological sis includes sialadenitis and various benign and malignant neo-
features and they must always be considered in the differential diagnosis plasms, such as myoepithelioma, proliferative and nodular fascii-
of sino-nasal neoplasms. tis, solitary fibrous tumour, spindle cell sarcoma, fibrosarcoma
etc. Therefore, a comprehensive histopathological assessment is
necessary.
E-PS-11-006
Spindle cell carcinoma:a unique and rare neoplasm
I. Kourtesis 1 , K. Koulia 1 , A. Tsavari 1 , K. Manoloudaki 1 , G. E-PS-11-008
Sotiropoulou2, T. Vasilakaki1 Odontogenic developmental cysts: reclassification according to the
1
Tzaneio General Hospital of Piraeus, Greece, 2 General Hospital of 2017 World Health Organisation Classification
Korinthos Greece I. Msakni1, F. Gargouri1, R. Hedhli2, N. Mansouri1, A. Saidi1, A.
Bouziani1, B. Laabidi1,2
1
Background & Objectives: Spindle cell carcinoma (SPCC) is an un- Pathology Department; Military Hospital for Instruction of Tunis,
common subtype of squamous cell carcinoma. It is a biphasic tumour Tunisia, 2 Tunis El Manar University, Medicine School of Tunis
consisting of a combination of squamous cell carcinoma (in situ or inva- Military Hospital of Tunis, Department of Pathology, Tunisia
sive) and a malignant spindle cell component with a mesenchymal ap-
pearance but of epithelial origin. Background & Objectives: Odontogenic developmental cysts is a
SPPC is observed mainly in the larynx especially in the glottic region. heterogeneous group that has undergone many changes in the
Its rarity and histopathological pattern poses a diagnostic challenge. new World Health Organisation (WHO) published in 2017.
Methods: A 66-year-old man presented with a ten-month history of Odontogenic keratocysts and Calcifying odontogenic cysts consid-
hoarseness of the voice and dyspnea. Laryngoscopic examination re- ered a neoplasia in the 2005 WHO classification are now consid-
vealed a polypoid mass 1,8cm. in dimension on the right vocal cord. ered developmental lesions. Orthokeratinized odontogenic cysts
Lymph nodes were not palpable. The mass was removed endoscopically. were considered a variant of the odontogenic keratocysts. In the
Results: Histological examination revealed a tumour showing foci of new 2017 WHO classification, it has been considered as a separate
well differentiated squamous cell carcinoma and a malignant spindle cell entity. Our aim was to reclassify these cysts according to the new
component which formed the bulk of the tumour. 2017 WHO classification.
In the immunohistochemical study the lesional cells (both squamous cells and Methods: It was a retrospective study of odontogenic developmental
spindle cells) were positive for CK5/6,P63,pankeratin and vimentin and negative cysts collected in our department over a period of 5 years (2012-2017).
for CD34,desmin,actin and S100p. The diagnosis was spindle cell carcinoma. Results: We collected 12 odontogenic developmental cysts. Dentigerous
Conclusion: Spindle cell carcinoma is a rare tumour. cyst was observed in 6 cases. The median age was 34 years (sex
Surgical excision combined with adjuvant radiotherapy has a better sur- ratio=1).Odontogenic keratocyst was observed in 5 cases.The median
vival outcome. age was 44 years (sex ratio=4). Orthokeratinized odontogenic cyst was
observed in a single 25-year-old male patient.
Three dentigerous cyst were reclassified to 2 radicular cysts and one
E-PS-11-007 inflammatory collateral cysts. Three odontogenic keratocyst were
Inflammatory myofibroblastic tumour of the parotid gland: report of reclassified to one dentigerous cyst, one orthokeratinized odontogenic
a rare case cyst and onefibro-dentinoma.
I. Kourtesis1, K. Koulia1, A. Tsavari1, G. Sotiropoulou2, T. Vasilakaki1, Conclusion: In our study, histological diagnosis after revision of the
K. Manoloudaki1 slides and anatomoclinical confrontation did not agree with the initial
 Virchows Arch

diagnosis in 50% of cases (n = 6).This is due, to the lack of clinical and neoplastic epithelial cells were positive for Cytokeratin and EMA, while
radiological data for the pathologist, but also to the absence odontogenic the sarcomatous component was positive for Vimentin, bcl2 and CD99.
cysts classification up to the year 2017. Additional molecular analysis revealed t (X;18) translocation of the SYT
gene with the detection of the SYT-SSX1 fusion type. Surgical margin
was free of tumour.
E-PS-11-010 Conclusion: Synovial sarcoma is a rare malignant tumour, which can
Adenoid cystic carcinoma with cervical spine metastasis: case report occur in the head and neck region. Tonsillar synovial sarcoma should
A. Kilitci1, Z. Asan2, E. Tugcugil3, î Aykanat2, A. Yüceer2, F. Durna4 be considered in the differential diagnosis when working up a tonsillar
1
Ahi Evran University Medical Faculty, Dept of Pathology, Turkey, 2 Ahi mass. In such rare cases, preoperative incisional biopsy could be consid-
Evran University Medical Faculty, Dept of Neurosurgery, Turkey, ered to aim with optimal surgical strategy.
3
Karadeniz Technical University Medical Faculty, Dept of
Anesthesiology, Turkey, 4 Ahi Evran University Training and Research
Hospital, Dept of Neurosurgery, Turkey E-PS-11-012
Components of the peritumoral zone of laryngeal carcinoma as ad-
Background & Objectives: Adenoid cystic carcinoma (ACC)s are ma- ditional morphological criteria of tumour aggressiveness
lignant tumours that typically originate from glandular structures and A. Semenova1, A. Shamanova1, E. Kazachkov2, A. Gyz1, T. Shamaeva2,
demonstrate metastasis by local invasion and via the hematogenous route E. Glazirina2
1
at advanced stages. Involvement of neighboring organs is also common. Chelyabinsk Oncology Clinic, Russia, 2 South-Ural State Medical
The literature does not include any cases of ACC with vertebral University, Russia
metastasis.
Methods: 45-year-old male patient was evaluated for findings of sudden Background & Objectives: To characterise the morphological features
neck pain and nearly total loss of strength in the right arm.His medical of the components of peritumoral zone in laryngeal carcinomas depend-
history revealed that he had been under follow-up for five years due to a ing on the degree of differentiation, the presence metastases.
diagnosis of ACC with a parotid gland origin.Cervical CT and MRI Methods: The object of the study was the surgical material of 94
examinations determined compression fracture in the corpus of C5 and patients with laryngeal squamous cell carcinoma, which was formed
spinal cord compression.The case,who did not report a history of depending on the degrees of tumour differentiation (G1=32, G2=32,
trauma,was urgently operated considering that the vertebral fracture could G3=30). Further, the material was grouped according to the presence
be a pathological fracture. (n = 33) or the absence of metastases in the lymph nodes of the neck
Results: Vertebral resection was made. Histopathological examination of (n = 86). Immunophenotyping of microenvironment components
the specimen revealed a tumour with solid and cribriform pattern that was was carried out.
composed of atypical epithelial and myoepithelial cells. The case, whose Results: When the degree of differentiation from G1 to G3 chang-
motor deficit showed partial improvement following corpectomy, es, were increases of cells which positive to CD7, CD8, CD56,
underwent rehabilitation in the postoperative period. The case who had CD79a, CD20, CD68, CD15 antibody (p<0.001). High cell level
been followed-up for metastases in the neck area and in intracerebral (210.0 cells positive to CD8 antibody, 587.0 (CD79a), 345.0
structures and who had undergo combined radiotherapy and chemother- (CD20), 428.0 (CD15) is a significant additional marker of metas-
apy died two years later due to multi-organ metastasis. tases in the cervical lymph nodes. In the presence of metastases in
Conclusion: No information could be found in the literature regarding the lymph nodes, the volume density of collagen and reticular
the vertebral metastasis of ACC. In these cases, localized tumourous fibers of microenvironment significantly increases. The volume
formations are treated with radiotherapy, while chemotherapy is admin- density of the blood and lymphatic vessels is not significantly
istered for multi-organ involvement. Vertebral metastasis can lead to path- different.
ological fractures. Conclusion: Сomponents of microenvironment of laryngeal carcinoma
have morphological features characteristic of different degrees of tumour
differentiation and depend on the presence of metastases in the cervical
E-PS-11-011 lymph nodes.
Synovial sarcoma of the palatine tonsil: a case report
J. Rajc1, K. Marjanović1,2, V. Zubčić3,2, B. Dumenčić1,2, S. Nekić1,2, D.
Dumić1,2 E-PS-11-013
1
Clinical Department of Pathology and Forensic Medicine, Osijek Lymph node metastasis of the epithelial component with squamous
University Hospital, Croatia, 2 Faculty of Medicine, University of differentiation of biphasic synovial sarcoma in the head and neck
Osijek, Croatia, 3 Clinical Department of Maxillofacial Surgery, Osijek region
University Hospital, Croatia L. Lozneanu1, B.M. Cobzeanu2, M.D. Cobzeanu2, G. Bandol3, I.D.
Florea4
1
Background & Objectives: Most synovial sarcomas arise in the extrem- "Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania,
2
ities (80%), with only 3-5% located in the head and neck region. We Department of Otorhinolaryngology, Faculty of Medicine, "Grigore T.
report a case of synovial sarcoma based in the palatine tonsil, as an Popa" University of Medicine and Pharmacy, Iasi, Romania,
3
extremely rare primary site of involvement. Department of Surgery, Institute of Regional Oncology, Iasi,
Methods: A 51-year-old man presented with sore throat and dysphagia. Romania, 4 Department of Morphofunctional Sciences II-Immunology,
On the physical examination, a palpable pedunculated right tonsillar "Grigore T. Popa" University of Medicine and Pharmacy, Iaşi, Romania
mass, with no cervical lymphadenopathy was noted. An MRI showed a
well-demarcated solid mass confined to the tonsil, measuring 3.6 cm in Background & Objectives: Synovial sarcoma (SS) is rarely diagnosed
greatest dimension with no involvement of the other surrounding struc- in the head and neck region. SS has predilection for middle aged adults.
tures. The patient underwent a tonsillectomy. We report a rare case of biphasic SS in the soft tissues of the neck with
Results: Intra-operative frozen section showed a malignant mesenchymal lymph node metastasis of epithelial component with squamous differen-
tumour along with the remnant of normal tonsillar tissue. Histological and tiation, of the biphasic SS.
immunohistochemical investigation showed a biphasic synovial sarcoma A 46 years old female patient was hospitalized for metastatic
with gland-like structures, lined by cuboidal/columnar cells. The laterocervical adenopathy with unknown primary site.
Virchows Arch

Methods: The patient underwent imagistic analysis and surgical excision, Background & Objectives: Epitheloid hemangioendothelioma is a rare
followed by histopathological examination through routine staining and low-grade vascular tumour with unpredictive cours, first classified by
immunohistochemistry. Weiss and Enzinger in 1982 as having “not completely benign clinical
Results: The magnetic resonance imaging of the cervical region indicated behavior” . Since then more than 200 cases and a lot of data had been
a tumoral mass associated with laterocervical adenopathy. The patient gathered about the clinical presentation and metastatic potential of these
was treated surgically with wide local excision. The histopathological tumours. We report on a 53-year-old female patient with a multifocal
examination of the cervical tumoral mass revealed a biphasic proliferation ulcerative tumour nodules in the external ear and retroauriclar space.
with high mitotic rate consisting predominantly of spindle cells. The Methods: Routine biopsy examination was performed with additional
lymph node presents metastasis comprising sheets of keratinized squa- immunohistochemistry.
mous cells. Immunohistochemistry for cervical tumour and lymph node Results: Histology revealed epitheloid cells, some with intracytoplasmic
showed diffuse positivity for TLE1, weak positivity for CD99 and posi- lumens, forming abortive vascular structures and small cell groups em-
tivity for cytokeratin AE1/AE3 and p63 markers in epithelioid component bedded in myxoid stroma. IHC for conformation of the vascular origin
of the cervical tumour and in the lymph node metastasis. was performed. In some of the regional lymph nodes there was extensive
Conclusion: Taking into account the above mentioned results, a metasta- vascular transformation, raising the suspicion of metastatic disease.
tic lesion of SS with squamous differentiation was considered. At the Immunohistochemically the tumour cells were positive for vascular
same time, we cannot exclude a lymph node metastasis of a squamous markers, such as CD34, ERG and negative for CK AE1-AE3.
carcinoma with unknown primary site. SS metastasis could be Conclusion: Although rare, we should increase our awareness of
overdiagnosed and this can lead to wrong therapeutic management. еpitheloid hemangioendothelioma, which must be differentiated from
Additional exams are mandatory to exclude a primary squamous tumour other more aggressive tumours such as metastatic carcinoma and
in the case of biphasic SS with squamous differentiation. angiosarcoma. Applying the accepted histologic criteria and with the
adjunct of IHC this distinction appears relevant due to the different sur-
vival rate and evolving therapeutic options.
E-PS-11-014
Lymphoma of mandible: a case report
P. Tziakou1, E. Delliou2, V. Papamichail3, A. Zizi-Sermpetzoglou1 E-PS-11-016
1
Department of Pathology of Tzaneio General Hospital of Piraeus, EGFR and Bcl-2 expression as a prognostic marker in head and neck
Greece, 2 Laboratory of Pathology - Xanthi, Greece, 3 Laboratory of squamous cell carcinoma (HNSCC) - a tissue microarray (TMA)
Pathology "ISTODOMI" - Piraeus, Greece based study in a resource-poor setting
S. Phaniraj1, J. Krishnamurthy1
1
Background & Objectives: Non-Hodgkin’s lymphomas are a group of JSS Medical College, JSS University, Mysore, India
neoplasms that originate from the cells of the lymphoreticular system.
Forty percent of non-Hodgkin’s lymphomas arise from extra nodal sites. Background & Objectives: Epidermal growth factor receptor
Non-Hodgkin’s lymphomas detected primarily in the bone are quite rare, (EGFR) and B-cell lymphoma-2 (Bcl-2) are critical mediators of
but among jaw lesions, they are more frequently present in the maxilla signal transduction pathways in HNSCC. This study was undertak-
than in the mandible. In the reported cases, 0.6% are found in the en to assess the expression of EGFR and Bcl-2 in HNSCC cases
mandible. according to the new scoring system, and to evaluate their associ-
Methods: We report a case of a 53-year-old male who presented with ation with various clinicopathological prognostic factors and pa-
painless swelling of the jaw. Radiographic examination and incisional tient survival.
biopsy were performed. Methods: A total of 60 surgically resected cases of HNSCC were studied
Results: The histopathological exam showed a diffuse proliferation of for expression of EGFR and Bcl-2 by immunohistochemistry on manual
atypical medium-sized lymphoid cells. Immunohistochemical analysis tissue microarray (TMA). EGFR expression was scored by proportion
revealed that tumour cells expressed immunopositivity for CD20, score (PS), intensity score (IS) and total score (TS) while Bcl-2 cytoplas-
CD79a, PAX5, bcl2, bcl6 and Ki67 and negative expression for CD3 mic staining was scored as either positive or negative. These were then
and EMA. A diagnosis of diffuse, high-grade, large B-cell NHL was correlated with known prognostic factors and patient survival.
confirmed. Results: High EGFR TS was recorded in 88.3% cases and Bcl-2
Conclusion: Lymphomas of the oral cavity typically present as positivity in 80% cases. A significant correlation was observed
intraosseous lesions, most commonly DLBCL. Viral infections between EGFR TS and perineural invasion (PNI) [p=0.017],
and immunological elements have been proposed as major contrib- whereas a trend toward significance was observed with tumour
uting factors. Most common chromosomal abnormality associated size and lymphovascular invasion (LVI). Bcl-2 positivity correlat-
with NHL is (14; 18) (q32; q21). The most common manifestations ed with nodal stage [p=0.023]. Survival analysis showed better
are pain, discomfort and swelling in the jawbone. They may imi- outcome in patients with lower EGFR PS and Bcl-2 negativity
tate a dental infection or any odontogenic process. Hence, the as also in patients with inherently better prognostic factors (non-
diagnosis of lymphoma is often delayed. Though lymphoma of smokers, females, carcinoma of tongue, well differentiated tu-
mandible is rare, it must be considered in differential diagnosis mours, cases without PNI, stages T1 & T2 and stages N0 & N1).
of swellings arising in that region. Prognosis is excellent in local- Conclusion: Our data demonstrate that EGFR and Bcl-2 overexpression
ized disease, whereas in disseminated disease, it is less favourable. are markers of what is considered to be more advanced disease. This
They may be effectively managed by chemotherapy alone. suggests that EGFR and Bcl-2 can be used as prognostic markers and
possibly as predictive markers for targeted therapy in patients with locally
advanced HNSCC.
E-PS-11-015
Epitheloid hemangioendothelioma of external ear and periauricular
area: one case report of a rare tumour E-PS-11-017
M. Genadieva-Yordanova1, A. Vlahova2, P. Stanimirov2, D. Dikov3 Association of tumour budding and number of metastasized lymph
1
Aleksandrovska University Hospital, Bulgaria, 2 Aleksandrovska nodes in laryngeal carcinomas
University Hospital, Bulgaria, 3 Centre Hospitalier de Marne-la-Vallee, A.P. Rodrigues1, E. Muhongo1, E. Amaral1, J. Pardal1
1
France Hospital de Braga, Portugal
 Virchows Arch

Background & Objectives: Tumour budding, described as the presence retroperitoneum or the adrenal gland. Ganglioneuroma of the head and
of single cells or small clusters of up to five tumour cells at the invasive neck region, including parapharyngeal space, is extremely rare diagnosis,
margin, is an established adverse prognostic factor for a few carcinomas. especially in adult patients (six reported cases). Most ganglioneuromas
Its unquestionable prognostic value in colorectal carcinomas raises the usually present as a slowly enlarging, asymptomatic mass found inciden-
question whether such prognostic value can also be present in other types tally. The aim of this report was to present a rare ganglioneuroma case in
of carcinoma. In the current study, we addressed laryngeal carcinomas parapharyngeal location.
and aimed to determine if there is a relation between tumour budding and Methods: A 70-year-old female presented with a 7 cm-sized tumour on the
the number of metastasized lymph nodes, an already established prog- left side of the neck and difficulty in swelling. Clinically the tumour of the left
nostic factor for this pathology. parotid gland was suspected. Ultrasonography revealed a lesion measuring
Methods: The surgical specimens of thirty-nine patients with primary 3.2 × 2.9 x 1.9 cm with inhomogeneous echogenicity. Computed tomography
larynx carcinomas were included. The presence of tumour budding was demonstrated a well-circumscribed, smooth-contoured, solid tumour located
determined through assessment of all tumour-containing H&E slides in the left parapharyngeal space without connection to the parotid gland.
using the “hot spot” approach. The cases were grouped as having mild Deformation of oropharynx with lateral displacement of cervical vessels were
budding when up to 4 tumour buds were identified; moderate, for 5 to 9 present. There was no features of invasion of surrounding structures.
tumour buds and marked for 10 or more tumour buds. The number of Results: An open biopsy of the lesion was performed. Histopathological
lymph nodes involved by metastasis per case was also recorded. examination revealed tumour comprising of spindle cells similar to neu-
Results: Mild, moderate, and marked budding was observed in 12 rofibroma crossing each other in an irregular fashion with mature gangli-
(30,8%), 20 (51,3%), and 7 (17,9%) cases, respectively. Cases with on cells lying singly and in clusters. On immunohistochemical analysis,
marked and moderate budding were associated with higher number of the tumour cells stained positive for synaptophysin, S100 and neuron
metastasized lymph nodes comparatively to cases with mild tumour bud- specific enolase, which confirmed ganglioneuroma diagnosis.
ding (p=0,044). Conclusion: Reported case increase awareness of ganglioneuroma
Conclusion: Our results demonstrate that higher tumour budding is as- occurence in the adult patient population. It is important to remember
sociated with increased number of metastasized lymph nodes, hinting that about this rare entity, especially evaluating biopsy specimens.
it could be a valuable prognostic factor for laryngeal carcinomas. We are
currently extending our cohort to address if tumour budding is an inde-
pendent prognostic factor. E-PS-11-020
Cribriform adenocarcinoma of minor salivary gland with cervical
lymph nodes metastases: a case report highlighting the significance
E-PS-11-018 of cytology
Biphenotypic sinonasal sarcoma – a new and rare entity O. Kuczkiewicz-Siemion1, M. Chraszczewska1, O. Stanowska1, M.
C. Quadros1, I. Alves1 Durzynska1
1 1
CHULN - Hospital de Santa Maria, Portugal Maria Sklodowska-Curie Institute - Oncology Center, Department of
Pathology and Laboratory Medicine, Poland
Background & Objectives: Biphenotypic sinonasal sarcoma (BSNS) is
a rare sinonasal tumour recently added to the WHO classification with Background & Objectives: Cribriform adenocarcinoma of minor salivary
only few cases described so far. Herein, we present a case of BSNS from gland (CAMSG) is a rare low-grade malignancy of salivary glands presenting
our routine practice. cytologic features resembling papillary thyroid carcinoma (PTC) without
Methods: A 55-year-old woman that presents with progressive obstruc- expression of TTF-1 and thyroglobulin. Commonly the first manifestation
tion of the left nasal cavity, without other symptoms. A CT-scan revealed of disease are cervical metastases. Although fine-needle aspiration biopsy
a soft-tissue mass that was removed endoscopically. (FNAB) is a method of choice in peripheral lymphadenopathy diagnosis,
Results: A polypoid mass with 4,5 cm in greatest dimension, grey with there are only three publications evaluating CAMSG cytology. The aim of
cystic areas filled with white gelatinous material was received. this report was to present a CAMSG case in the light of cytological features,
Histologically, a spindle-cell proliferation arranged in intersecting fasci- thus enriching the spectrum of FNAB differential diagnosis.
cles with a monotonous appearance was observed. No mitosis or necrosis Methods: We report a case of 76 year-old female with submucosal tumour of
were noted. The neoplastic cells showed diffuse immunoexpression to the pharynx. The patient presented two solid lesions diagnosed accidentally by
TLE-1, partially to S100 and focally to SMA and myogenin, without cervical ultrasonography. In physical examination slightly enlarged subman-
cytokeratin expression. Due to the morphology, immunohistochemistry dibular lymph node was detected. Computed tomography revealed a lesion
results and location, the critical differential diagnosis comprised BSNS (22x18x24mm) situated in the masticator and the parapharyngeal space.
and monophasic synovial sarcoma. The molecular studies directed to Results: FNAB of submandibular lymph node showed cribriform, dense
SYT and MAML3 genes demonstrated MAML3 gene rearrangement, clusters of monomorphic round-oval tumour cells with scant cytoplasm,
corroborating the diagnosis of BSNS. which was inconclusive. Subsequently, an open biopsy was conducted.
Conclusion: BSNS is a low-grade sinonasal sarcoma with neural and Histologically, the tumour was composed of oval, overlapping cells with
myogenic features, which has a slowly progressive growth that may recur bright nuclear chromatin and nuclear grooves. Cells formed cribriform,
locally and has no metastatic or death-related outcomes associated. papillary and solid structures. Immunohistochemistry panel revealed:
TTF-1 (-), thyroglobulin (-), S100 (+), p63 (+), Gal-3 (+), CK19 (+)
focally. Status of EBV and HPV by hybridization in situ was negative.
E-PS-11-019 Conclusion: CAMSG could be misdiagnosed as PTC or other tumour
A case report of non-paediatric ganglioneuroma of parapharyngeal presenting similar cytological and morphological features. In view of
space: an important pitfall in differential diagnosis frequent node metastases observed in this tumour, appropriate evaluation
M. Chraszczewska1, O. Kuczkiewicz-Siemion1, M. Durzyńska1 of cytological smear seems to be crucial for patient management and
1
Maria Sklodowska-Curie Institute - Oncology Center, Department of allows establishing final diagnosis and treatment.
Pathology and Laboratory Medicine, Poland

Background & Objectives: Ganglioneuroma is a rare benign tumour E-PS-11-021

arising from the neural crest cells and generally occurs in children and Clear cell carcinoma of the nasopharynx: report of two new cases
young adults. It is commonly localized in the posterior mediastinum, the J. Filipe1, M. Rito1,2, I. Fonseca1,2
Virchows Arch

1
Serviço de Anatomia Patológica, Instituto Português de Oncologia de independent factors affecting the prognosis of patients with adenoid cys-
Lisboa Francisco Gentil, Lisbon, Portugal, 2 Instituto de Anatomia tic carcinoma of salivary glands.
Patológica, Faculdade de Medicina, Universidade de Lisboa, Portugal

Background & Objectives: Clear cell carcinoma (CCC) is a rare low- E-PS-11-026
grade salivary gland neoplasm, accounting for <1% of all salivary tumours. Mucoepidermoid carcinoma of salivary glands: a clinical study of 22
Most cases occur in the minor salivary glands of the oral cavity, mainly at cases and review of the literature
the palate and tongue. Its morphological diagnosis is challenging since it is I. Dimitriadis 1 , K. Vaxtsevanos 2 , A. Cheva 3 , A. Baliaka 1 , S.
often confused with other clear cell-rich neoplasms. EWSR1-ATF1 gene Papaemmanouil1
1
fusion supports the diagnosis. Nasopharyngeal involvement is uncommon, Department of Pathology, General Hospital of Thessaloniki "G.
with few cases described. Due to its rarity and diagnostic difficulty, we Papanikolaou", Greece, 2 Department of Oral and Maxilofacial Surgery,
present two cases of primary nasopharyngeal CCC. General Hospital of Thessaloniki "G. Papanikolaou", Greece,
3
Methods: Two cases of nasopharyngeal CCC are described, along with a Department of Pathology, Aristotle University of Thessaloniki, Greece
review of the literature.
Results: A 77-year-old female (1) and a 67-year-old-male (2) clinically Background & Objectives: Mucoepidermoid carcinoma (MEC) is a
presented with a history of hearing loss and epistaxis. Imaging studies malignant tumour with a widely diverse biological behavior. The purpose
revealed an expansive lesion in the lateral wall of the nasopharynx (1) and of this study was to analyse the clinicopathological characteristics of this
an infiltrative lesion in the posterior wall surrounding the internal carotid neoplasm.
artery (2). Microscopically the tumours were similar, with a nested and Methods: Between 1997-2017, (22) patients with MEC were treated in
trabecular pattern in a hyalinized stroma, composed by cells with distinct the Clinic of Oral/Maxillofacial Surgery. The age range was 26-84 years.
borders, round to oval nuclei, pale eosinophilic and clear cytoplasm. A The distribution of the primary sites was: hard/soft palate (8), parotid (6),
diastase-sensitive positive PAS reaction revealed the presence of buccal mucosa (5), and tongue (3). All patients were treated radically with
intracytoplasmic glycogen, and tumour cells were positive for AE1/ surgery. The expression of the Ki-67 was evaluated on a subset of all
AE3 and p63. Rearrangements of the EWSR1 gene were found by cases.
FISH, confirming the diagnosis. Results: Lymph node metastases occurred in one patient. The Pearson
Conclusion: Although rare, nasopharyngeal CCC should be considered chi-square statistical analysis was used for comparing the Ki-67 values in
in the differential diagnosis of nasopharyngeal neoplasms and represent a correlation with histological grade of the tumours. The Ki-67 expression
diagnostic challenge. An accurate diagnosis is relevant as these patients was 2-3% in low-grade, in intermediate-grade it was estimated (4-8%)
have indication for radiotherapy alone but not for chemoradiotherapy as and the high-grade tumours had increased expression (70%) of tumour
do for the common nasopharyngeal carcinoma. cells.(50%) of tumours were classified as low grade, (18,18%) as inter-
mediate and (31,81%) as high-grade MECs. Positive surgical margins
were documented in (8)cases (36,3%). The 5-year overall disease specific
E-PS-11-025 survival rate was 85%. Statistical analysis demonstrated that the factor
Adenoid cystic carcinoma of salivary glands. A study of 40 cases with that significantly correlated with overall survival was the histological
clinicopathologic correlation grade of tumours (p=0.013). Poorer survival was observed in patients
I. Dimitriadis 1 , G. Venetis 2 , D. Anestakis 3 , N. Pastelli 1 , S. aged >50 years.
Papaemmanouil1 Conclusion: Complete surgical excision is the treatment of choice for
1
Department of Pathology, General Hospital of Thessaloniki "G. MECs. Multivariate analysis demonstrated that the factor that significant-
Papanikolaou", Greece, 2 Department of Oral and Maxilofacial Surgery, ly correlated with overall survival was the histological grade of tumours.
General Hospital of Thessaloniki "G. Papanikolaou", Greece, The immunohistochemical study of Ki-67 expression may provide addi-
3
Department of Autopsy Histopathology, Aristotle University of tional prognostic information for this tumour.
Thessaloniki, Greece

Background & Objectives: Adenoid cystic carcinoma occurred more E-PS-11-027

commonly in the minor salivary glands. This study was to analyse the Clear cell ameloblastic carcinoma of the maxilla - an extremely rare
clinicopathological characteristics of this neoplasm. odontogenic tumour
Methods: All the cases recorded in our hospital from 1996-2017 were L. Manojlovic1, K. Krstanac1, P. Senjug2, S. Manojlovic1,3
1
assessed. Age, gender, anatomical location, and histology of all the spec- Department of Pathology and Cytology, University Hospital Dubrava,
imens were evaluated. Between 1985-2000, (40) patients with ACC of Zagreb, Croatia, 2 Unit of Nephropathology and Electron Microscopy,
salivary glands were treated in the Clinic of Oral/Maxillofacial Surgery. Department of Pathology and Cytology, Dubrava University Hospital,
The age range was 22-87 years. The distribution of the primary sites was Zagreb, Croatia, 3 University of Zagreb, School of Medicine, Croatia
buccal mucosa (19), floor of the mouth (5), hard /soft palate (6), parotid
(4), and tongue (6). All the patients were treated radically with surgery. Background & Objectives: Maxillary clear cell variant of ameloblastic
Results: Univariate analysis revealed that the factors impacting the prog- carcinoma (AMEC) is exceedingly rare and diagnostically challenging.
nosis were age, presence (14 patients) or absence (26 patients) of nerve Treatment modalities are still debated.
invasion, histological subtypes, (37: Gr2, 3:Gr3) ,clinical stage, positive Methods: We present a case of a 56-year-old male with swelling
(13) or negative (27) surgical margin. Patients aged >50, presence of around the second right maxillary molar. Orthopantomography re-
nerve invasion, solid/tubular subtype, advanced clinical stage (stages vealed a well delineated radiolucent lesion. A biopsy revelead alve-
III-IV), and positive surgical margin had poorer prognosis than those aged olar nests of large atypical epithelial cells with vesicular nuclei and
<50, absence of nerve invasion, cribriform subtype, early clinical stage clear cytoplasm, high mitotic activity, central necrotic foci and pe-
(stages I-II), and negative surgical margin. Multivariate analysis showed ripheral palisading, suggesting ameloblastic differentiation.
that the presence of nerve invasion, solid histological subtype, advanced Immunohistochemical analysis excluded the possibility of metasta-
clinical stage (stages III and IV), and positive surgical margin were inde- sis or clear cell salivary gland carcinoma. The tumour expanded
pendently associated to poor prognosis. rapidly, therefore the patient underwent primary radiotherapy resulting
Conclusion: Presence or absence of nerve invasion, histological subtype, in tumour regression. Surgical treatment followed. Three years follow-up
clinical stage, and positive or negative surgical margin are the revealed no evidence of recurrent or metastatic disease.
 Virchows Arch

Results: Malignant intraosseous epithelial tumours are most frequently oropharyngeal HPV-LCNEC have been described. We report a new case
metastases, therefore the diagnosis of primary intraosseous carcinoma of this very rare entity.
must be made by exclusion. At present, there is no single definitive Methods: a 51-year-old woman, without history of cancer, smoking or
microscopic criterion for AMEC. The lack of specific histologic, immu- alcohol habits, presented a large necrotic polypoid tumour of the base of
nohistochemical, and ultrastructural markers to confirm the odontogenic the tongue, vallecula and epiglottis, with bilateral cervical lymphadenop-
origin of these lesions, makes diagnosing it very difficult. The presence of athies. Pet Scan and TDM highlighted disseminated bilateral pulmonary
palisading and many clear cells strongly suggests an ameloblastic carci- metastases and mediastinal lymphadenopathies.
noma. Early and complete removal of the tumour offers the best chance of Results: On biopsies, the aspect was that of a highly necrotic and mitotic
survival. In our case, due to aggressive growth of the tumour, primary (> 100 mitoses/2mm²) large cell undifferentiated carcinoma. Tumour cells
radiotherapy was performed achieving an excellent result. were positive for some epithelial (CK AE1/AE3, EMA) and neuroendo-
Conclusion: AMEC is a very rare odontogenic neoplasm. Differential diag- crine markers (Chromogranin B, Synaptophysin, CD56 and INSM1).
nostics are demanding, and treatment modalities are still disputed. According Chromogranin A, CK5-6, p63, p40, PS100, TTF1 and NUT were nega-
to our experience and a review of literature, preoperative radiotherapy of such tive. Proliferative Index (Ki67) was 90%. p16 was overexpressed and
aggressive tumour greatly increases the chances of a positive outcome. high-risk HPV was evidenced by Chromogenic In Situ Hybridization
(CISH). The diagnosis of HPV-LCNEC was established. The patient
was treated by chemotherapy.
E-PS-11-028 Conclusion: In oropharynx, HPV-LCNEC is an uncommon variant
Chondromyxoid fibroma of craniofacial bones - report of three cases of HPV-related OPC, even rarer than HPV-related SmCC. It’s cru-
K. Krstanac1, L. Manojlovic1, P. Senjug2, S. Manojlovic1,3 cial to identify by immunohistochemistry the neuroendocrine differ-
1
Department of Pathology and Cytology, University Hospital Dubrava, entiation of these oropharyngeal carcinomas, because HPV-related
Zagreb, Croatia, 2 Unit of Nephropathology and Electron Microscopy, NEC are very aggressive, their treatment and prognosis being very
Department of Pathology and Cytology, Dubrava University Hospital, different from that of the classical HPV-related non keratinizing
Zagreb, Croatia, 3 University of Zagreb, School of Medicine, Croatia OPC, which prognosis is good.

Background & Objectives: Chondromyxoid fibroma (CMF) is unusual

in craniofacial localization, frequently showing bone erosion or destruc- E-PS-11-030
tion, which could be misdiagnosed as malignancy. Lengarhans cell hystiocytosis of cranial bones - diagnostic challenge
Methods: We present three cases of CMF diagnosed over the last 18 J. Sopta1, L. Simic1, G. Djuricic2, M. Petrovic3
1
years in our Institution. The first case was a 24-year-old man with swell- Institute of Pathology, Medical Faculty, University of Belgrade, Serbia,
2
ing of the mandible, the second was a 53-year-old man with a tumour of Institute for Oncology and Radiology, Belgrade, Serbia, 3 Clinic for
the temporal bone and the third was a 36-year-old woman with swelling maxilofacial surgery, Belgrade, Serbia
of the temporomandibular area. CT analyses revealed radiopaque-
radiolucent well-circumscribed multilocular areas with fine trabeculation. Background & Objectives: Langerhans cell hystiocytosis (LCH) is a
The lesion of the temporal bone eroded the bone surface. Biopsies re- lesion characterised by the presence of cells with characteristics similar
vealed abundant myxoid matrix with scattered chondroid and spindled to bone marrow. Frequent localizations of LCH are cranial bones.
cells. The temporal bone tumour was misdiagnosed as chondrosarcoma. Methods: All cases of LCH (25) diagnosed in the cranial bones during 20
Histopathological analysis of surgical specimens revealed, lobulated, en- years at the Institute of Pathology, Medical Faculty, University of
capsulated nodules composed of chondroid tissue with bland Belgrade are included in study. Biopsies were stained by: HE,
chondrocytes and scattered multinuclear osteoclasts, surrounded by spin- Vimentin, S-100, CD1a, CD68, CD163, Langerin, LCA and Ki 67.
dled cells in a myxoid stroma. The final diagnosis in all three cases was Expression of CD1a and Langerin were analysed.
CMF. Follow-up revealed no signs of recurrent disease. Results: The majority of patients were male (57,2%), with average age
Results: CMF is a rare benign bone tumour, most commonly occuring in 2.14 ± 24.84 years (range 1–28 years). Frontal bone was the most fre-
the metaphyseal region of long bones in young adults. It is a locally quent localization (82%), followed by temporal bone. Tumour size ≥5cm,
destructive lesion with a high recurrence rate (>25%), but does not un- was observed in 3 (12%) of patients. The most common subtype was
dergo malignant transformation. Small biopsies or curettings may often eosynophilic granuloma 23 cases, Hand–Schüller–Christian and
lead to misdiagnosis. Although head and neck involvement is extremely Letterer–Siwe disease were diagnosed at one patient .
rare, CMF should be included in the differential diagnosis. All systemic and polyostotic forms of LCH were positive for both
Conclusion: CMF of craniofacial bones is exceedingly rare. Because of (CD1a and Langerin ) primary antibodies. Single bone disease pre-
its similarity to various malignant bone tumours, such as sentations (19 cases) had different immunoprofiles. The majority of
chondrosarcoma, diagnosing this tumour can be challenging, and requires cases 16/19 had coexpression of antibodies. CD1a was positive in 8
clinical, pathological and radiological correlation. cases were Langerin was negative. Sprucely, one biopsy showed
Langerin expression without CD1a positivity. In that case electron
microscopy was done, and Birbeck granules were confirmed into
E-PS-11-029 LCH cells.
Human Papillomavirus-related oropharyngeal high-grade large cell Conclusion: Histological appearance and immunophenotype of LCH
neuroendocrine carcinoma: a case report are in correlation with clinical presentation. CD1a antibody is more
O. Casiraghi1, C. Ngo2, N. Labaied2, A. Benlakhdar2 sensitive than Langerin, but Langerin is more specific for LCH. In
1
Gustave Roussy, France, 2 Gustave Roussy, Paris-Saclay University, LCH diagnostic procedure application of electron microscopy could
Biopathology Dèpartment, Villejuif, France be useful.

Background & Objectives: In the 2017 WHO classification, two sub-

types of poor differentiated neuroendocrine carcinoma (NEC) are de- E-PS-11-031
scribed, in the supraglottic larynx especially: large cell NEC (LCNEC) Laryngeal pleomorphic rhabdomyosarcoma: a case report
and small cell NEC (SmCC). In the oropharynx, only the HPV-related X. Ara-Mancebo1, C. Alborch1, E. Fuentes-Camps1, C. Romagosa Pèrez-
SmCC is mentioned, as an uncommon and aggressive variant of HPV- Portabella1, I. Ramos-Oliver1, S. Ramón y Cajal1, J. Temprana-Salvador1
1
related oropharyngeal carcinoma (OPC). A very few cases of Vall d'Hebron University Hospital, Spain
Virchows Arch

1 2
Background & Objectives: Rhabdomyosarcomas are rare soft tissue Department of Pathology Farhat Hached Hospital, Tunisia, Farhat
tumours in adults. They usually arise in lower extremities, in their alveolar Hached Hospital, Tunisia, 3 Pathologic Laboratory, Tunisia
variant –the other subtypes (embryonal, pleomorphic and spindle
cell/sclerosing) being less frequent. Thus, the diagnosis of a pleomorphic Background & Objectives: Salivary gland cystadenoma especially
rhabdomyosarcoma in an uncommon location, like the larynx (with only in the parotid gland is rare benign tumour that was clearly defined,
22 cases reported in the literature), poses a true challenge. in the second World Health Organization’s Histological
Methods: We report the case of a 66-year-old man, ex-smoker without Classification of Salivary Gland Tumours published in 1991, as a
other remarkable history, who sought medical consultation for a three- distinct histopathological entity. It’s characterised by predominantly
month history of catarrh, dysphony, odynophagia, left otalgia and dys- multicystic growth in which the epithelium demonstrates adenoma-
phagia. Endoscopy showed a submucosal lesion in the left arytenoid, tous proliferation. The epithelial lining is frequently papillary and
occupying the piriform sinus. ATC confirmed a 43x33x22mm infiltrative rarely mucinous.
lesion, without lymphatic node enlargement. A diagnostic incisional bi- This work highlights the clinical and histopathological features of mucin-
opsy was performed. ous cystadenoma of the gland parotid and its differential diagnosis.
Results: The histologic examination showed an intact epithelium along Methods: We describe a 33-year-old woman without clinical histo-
with a cellular proliferation with a mesenchymal pattern, composed of ry, who had a slowly painless enlarging tumour, 35mm in diameter,
epithelioid cells with a striking pleomorphism, and abundant eosinophilic in the superficial lobe of the right parotid gland. The tumour was
cytoplasm with polygonal outlines. Nuclei were irregular, with prominent surgically excised with wide margins under general anesthesia. The
hyperchromatic nucleoli. specimen was referred to the laboratory of pathological anatomy.
A broad immunohistochemical panel was performed: negative Grossly, the parotidectomy weighed 10gr and measured
cytokeratins (AE1/AE3, CAM5.2), p40 and EMA ruled out an epithelial 3.5×2.5×2 cm which contained a well circumscribed encapsulated
origin; negative HMB45, MelanA and S100, a melanocytic origin; neg- tumour with myxoid appearance, soft consistency and whitish color
ative synaptophysin and CD56, a neuroendocrine origin; and negative on cut section.
CD45, a lymphoid origin. Results: Histologically, the tumour was surrounded by a fibrous capsule
The rhabdoid morphology suggested a muscular origin, and desmin, and composed of multiple cystic spaces which were lined by tall colum-
myogenin and MyoD1 were positive. The diagnosis of pleomorphic rhab- nar mucus-producing cells. There was no cellular atypia or invasive
domyosarcoma was established. growth. The surrounded parotid parenchyma was without abnormalities.
Conclusion: In head and neck, one must rule out epithelial/squamous In view the complexity and histomorphological diversity of salivary
neoplasms and, secondly, undifferentiated tumours. Morphology is fun- gland tumours, the pathological differential diagnosis included a large
damental when considering a diagnosis, as identifying a rhabdoid pattern spectrum of benign and malign tumour like Papillary Cystadenoma,
was crucial in this case. Cyst Adenocarcinoma … The final histological diagnosis was
Mucinous cystadenoma, without signs of malignancy.
Conclusion: To the best of our knowledge, from analysis of the
E-PS-11-032 cases in the literature (1990-2018) we report the third case of
A rare case of villonodular synovitis with synovial chondromatosis of mucinous cystadenoma of parotid gland. Despite its benignity,
the temporomandibular joint follow up of the patient is necessary since recurrences, and a case
F. Kaya1, M.F. Acikalin1, A. Incesulu2 of malignant transformation to invasive micropapillary adenocar-
1
Eskisehir Osmangazi University, Department of Pathology, Turkey, cinoma in mucinous cystadenoma of parotid gland have been
2
Eskisehir Osmangazi University, Faculty of Medicine, Department of reported.
Otolaryngology-Head and Neck Surgery, Turkey

Background & Objectives: Pigmented villonodular synovitis (PVNS) E-PS-11-034

most commonly occurs within the large joints of the extremities. The The role of molecular pathology in the diagnosis of salivary gland
temporomandibular joint is the rare site of occurrence of the disease. tumours: new advances and "pitfalls"
Here we present a case of simultaneous occurrence of pigmented J. Costa1, S. Petronilho2, J. Vieira3, S. Lisboa3, M. Teixeira3, R.
villonodular synovitis and synovial chondromatosis (SC) in the temporo- Henrique2, M. Jácome2
1
mandibular joint (TMJ). Department of Pathology IPOP, Portugal, 2 Department of Pathology,
Methods: A 37-year-old female presented with a complaint of a enlarg- IPO-Porto, Portugal, 3 Department of Genetics, IPO-Porto, Portugal
ing mass at her right TMJ and hearing loss for 1.5 years. Computed
tomographic imaging demonstrated a soft tissue mass around the right Background & Objectives: Recent advances in the molecular char-
TMJ. The lesion was removed and sent to our laboratory. acterization of salivary gland tumours (SGT) have uncovered new
Results: Microscopically, the slices of gray-brown tissue were composed diagnostic markers and promising therapeutic targets. However, the
of nodules of synovium-like monocytes, small histiocytoid cells and mul- rapid advances in this field are often hard to integrate and interpret
tinucleated giant cells. There were hemosiderin deposits and aggregates of in routine practice.
foam cells. Immunohistochemically, histiocytoid cells were positive for D2- Methods: We reviewed the current literature and report two cases that
40, CD163 and CD68. They were negative for S100 protein, HMB-45, illustrate the strength and pitfalls of molecular testing of SGT during
keratin and desmin. Multinucleated giant cells were positive for CD68. routine practice. In case 1, an 11-year-old female disclosed a parotid
The slices of gray-white tissue are composed of loose bodies of SC. swelling with 6 months of evolution, whose scant biopsy material
Conclusion: A review of the English language literature revealed 3 cases prevented a conclusive diagnosis. In case 2, a 61-year-old female with a
of simultaneous PVNS and SC involving the temporomandibular joint. cervical mass with 8 months of evolution was biopsed.
Although rare in this location, PVNS should be considered in the differ- Results: Case 1: The biopsy revealed a solid and cystic tumour, with
ential diagnosis of aggressive preauricular swellings. cuboidal and mucous cells (CK7+/P63+) and histiocytes (CD68+), sugges-
tive of mucoepidermoid carcinoma(MEC). Detection of a MECT1-
MAML2 rearrangement confirmed the diagnosis of MEC. Case 2: The
E-PS-11-033 biopsy revealed a neoplasm with hyalinized stroma and clear cells (PAS+
Mucinous Cystadenoma of parotid gland: a case report ,CK7+,p63+). Identification of an EWSR1 rearrangement raised sus-
D. Chiba1, S. Chaieb2, S. Yacoub2, N. Beizig3, B. Sriha2 picion of a clear cell carcinoma(CCC). The examination of the
 Virchows Arch

surgical specimen, however, revealed a high-grade SGT mainly com- cases while the unicystic type accounts for 20% of cases. Wide surgical
posed of clear cells (CKAE1/AE3+,CK14+,p63+,HHF35+,CD10+ exegesis was performed in 66.7% of cases. The exeresis’ margins were
,calponin+,vimentin+), consistent with myoepithelial carcinoma(MC). infiltrated by the tumour in 33.3% of cases. Transformation into
Conclusion: Recent data has associated MECT1-MAML2 rearrange- ameloblastic carcinoma was identified in only one case.
ments with lower local aggressiveness and histologic grade. In SGT, Conclusion: Ameloblastoma is a locally aggressive tumour which can be
EWSR1 rearrangements have been reported in CCC, MC and rare cases associated with a significant local morbidity. This study confirms that a
of MEC. Reporting both fusion partners in the fusion gene is of the utmost wide surgical resection in the treatment of ameloblastoma appears to be a
importance. Molecular findings in SGT should be integrated alongside very important predictor of tumour clearance.
clinical, morphological and immunohistochemical features in a holistic
diagnostic approach.
E-PS-11-037
Lymphoepithelial carcinoma of the parotid gland: a rare entity
E-PS-11-035 B. Laabidi1,2, R. Hedhli3, R. Yaich1,2, F. Gargouri4, N. Mansouri1,2, A.
Perioperative finding of metastatic papillary cystic thyroid carcino- Saidi5, A. Bouziani4, I. Msakni4
1
ma presenting as lateral neck cyst Tunis El Manar University, Medicine School of Tunis, Tunisia,
E. Molnarova1, K. Kajo2, P. Veres1 and A. Stanikova1 2
Military Hospital of Tunis, Department of Pathology, Tunisia, 3 Tunis El
1
Medicyt s.r.o, Slovakia, 2 SZU Ustav patologie a Onkologicky ustav sv. Manar University, Medicine School of Tunis Military Hospital of Tunis,
Alzbety, Slovakia Department of Pathology, Tunisia, 4 Pathology Department, Military
Hospital for Instruction of Tunis, Tunisia, 5 Pathology Department;
Background & Objectives: Here we present a case of perioperative Military Hospital for Instruction of Tunis, Tunisia
finding of metastatic papillary thyroid carcinoma in the lateral cervical
lymph node cyst. Background & Objectives: Lymphoepithelioma-like carcinoma (LELC)
Results: Microscopy demonstrated foci of lymphoid tissue with a large of the salivary gland is a rare tumour accounting for 0.4% of all malignant
cystic structure containing papillary projections and accessory glandular salivary gland tumours. We present a rare case of LELC of the parotid gland.
elements resembling thyroid tissue. The cyst lumen was filled with hemo- Methods: A 61-year-old man was diagnosed with a mass in the left parotid
siderin laden macrophages. The epithelial lining of the large cyst and acces- gland with no other symptoms or past medical history. Ultrasound revealed
sory glandular structures consisted of a single layer of cuboidal cells hypoechoic, inhomogeneous mass of the parotid gland. Patient underwent
crowded nuclei and identified pseudonuclear inclusions. The epithelial lining surgical removal of the mass by a superficial parotidectomy.
showed focal apical cytoplasmic positivity for thyroglobulin, in addition to Results: Initial frozen sections analysis rendered a diagnosis of malig-
positivity for CK19, TTF, CKAE1/3. The Ki67 proliferation index was 1%. nancy. A complete neck dissection was performed. Histopathologic ex-
The Diagnosis of cystic metastatic papillary thyroid carcinoma a lateral amination of the specimens revealed a parotid gland with solid carcino-
cervical neck lymph node was made. Clinical, radiological and genetic matous sheets, trabeculae and isolated small groups of malignant epithe-
examination for occult papillary thyroid carcinoma was advised. lial cells intermingled with lymphoid stroma. The satellite lymph node
Conclusion: Metastatic papillary thyroid carcinoma should be consid- showed no infiltration. Immunohistochemical analysis showed neoplastic
ered in the differential diagnosis of clinically benign appearing cystic cells with positive staining for pancytokeratin and epithelial membrane
neck mass. Perioperative biopsy of these lesions should be indicated antigen and focal expression of LMP1. Lymphoid cells were positive for
and handled with care. Bearing in mind that clinical, biochemical and both CD20 and CD3 markers. On the basis of these findings, a diagnosis
imaging parameters are lacking for determining the definite diagnosis. of stage II, undifferentiated LELC of the parotid gland was made.
Conclusion: LELC of the salivary gland is a rare entity with a better
prognosis than other poorly differentiated tumours; surgical excision with
E-PS-11-036 post-operative radiotherapy is the treatment of choice.
Clinico-pathological features of ameloblastoma in the center of
Tunisia
E. Ben Hadj Khalifa1, N. Abdessayed2, D. Chiba2, H. Salifou1, S. Ben E-PS-11-038
Khalifa1, S. Jacoub1, B. Sriha1 Human papilloma virus (HPV)- related multiphenotypic sinonasal
1
Cytology and Pathology Department CHU Farhat Hached, Sousse- carcinoma: report of two cases
Tunisia, 2 Department of Pathology Farhat Hached Hospital, Tunisia I. Dumitru1, M. Wassef2,3, A.C. Baglin2,3, P. Hèlène4,3, A. Coste1, P.
Bedbeder1, A. Boyez1
1
Background & Objectives: Ameloblastoma is a rare odontogenic tu- CHI Créteil, France, 2 Lariboisière Hospital, France, 3 Paris, France,
4
mour which is known by its benignity despite a local expansive character. Hôpital Europèen Georges-Pompidou
This tumour is the most common odontogenic neoplasm after
odontoma.The nonspecific clinical and radiological presentations are re- Background & Objectives: HPV-related carcinoma with adenoid cystic
sponsible of pre-surgical misdiagnosis and an inadequate excision. The carcinoma-like features defines a rare HPV-related sinonasal neoplasm, a
aim of this study was to compare the clinical, radiologic and histopatho- provisional entity in the 2017World Health Organization Classification
logical results, surgical management, and evolution of patients with (WHO) of Head and Necktumor. Dr Justin Bishop, who initially de-
ameloblastoma with data reported in the literature. scribed this tumour in 2013, recently emphasized the fact that this tumour
Methods: The study included all cases of ameloblastoma diagnosed in the showeda morphologicalspectrum,broader than initially thought, and pro-
central region of Tunisia between 2005 and 2018. The data were extracted posed a new name: “HPV-related multiphenotypicsinonasal carcinoma”
from the clinical records of the cancer registry of the central region. (HMSC). We reporttwo cases ofthis neoplasm, which multiple samples
Results: 15 cases of histologically confirmed ameloblastoma were found show this histologic spectrum.
over a period of 14 years. They are divided into 8 men and 7 women. The Methods: Eight sinonasal samples were available from two patients (one
average age is 43.7 years. 78.6% of cases are developed in the mandible. female, one male, both 39 years old at initialdiagnosis). Each patient had
The most reported radiological aspects are an osteolytic image in 50% of two initial tumour samples and two recurrence samples.
cases and a unicystic image in 30% of cases. Macroscopically, the tumour Immunohistochemistry with p16, CD117, S100, p40, p63, CK5/6 anti-
measures 5.6 cm in average. It has a mixed solid-cystic appearance in bodies and HPV detection and genotyping (using theINNO-LiPA HPV
77.8% of cases. Microscopically, the follicular type represents 46.7% of Genotyping Extra II kit ) were performed.
Virchows Arch

Results: All samples showed highly cellular and mitotic proliferation of enlargement. She agreed to be submitted to a subtotal parotidectomy with
basophilic cells. facial nerve preservation.
Initial tumour samples from the male patient showed cribriform architec- Results: Clinically, it is predominant in women, with mean age of 60
tural foci, whereas these foci were not present in recurrence samples but years, more commonly in the parotid gland. It has potential to metasta-
highly atypical cells had appeared. Female patient samples showed crib- size. Grossly, it has 6 cm in length and has an expansive growth axis.
riform but also ribbon-like pattern and foci of squamous differentiation Histologically, it is characterised by a low grade, multinodular,
within the invasive tumour. intraglandular neoplastic lesion, noncapsulated, with epithelial and
Conclusion: Conclusion: HMSC has abroad histologic spectrum, not myoepithelial components - an outer rim of myoepithelial cells and inner
always reminiscent of adenoid cystic carcinoma, a fact pathologist should ductal cells with eosinophilic cytoplasm and round, insipid nuclei.
be aware in order to propose the appropriate diagnosis. Perineural invasion was identified.
Conclusion: This entity is a rare and its histological diagnosis is of great
significance, since it generally is a treatable low-grade tumour, but can
E-PS-11-039 have high grade transformation, hence the importance of correct diagno-
An unusual nasal mass sis and ressection.
A. Keogh1, S. Momdouh2, O. James Paul 3, S. McWilliams3, M.
Redmond4, H. Barrett4
1
Department of Histopathology, Beaumont Hospital, Ireland, E-PS-11-041
2
Department Otolaryngology, Head & Neck Surgery, Beaumont Hospital/ Carcinomas ex-pleomorphic adenomas: morphologic and
RCSI, Ireland, 3 Department of Radiology, Beaumont Hospital, Ireland, immunophenotypic criteria
4
Department of Histopathology, Beaumont Hospital, Ireland M. Tourne1, M. Wassef1, O. Casiraghi2, C. Badoual3, M. Lefevre4, S.
Albert1, A. Couvelard1, M. Hourseau1
1
Background & Objectives: We present the case of a 52-year-old female Bichat Hospital, APHP, France, 2 Gustave Roussy, France, 3 HEGP,
who presented with a two month history of nasal congestion, loose teeth APHP, France, 4 Montsouris Institute, France
and right maxillary pain.
Methods: Multiple imaging studies, biopsies and molecular testing were Background & Objectives: The etiological factors associated with car-
completed for investigation into this nasal mass. cinomas ex-pleomorphic adenomas (CXPA) are poorly defined, as are the
Results: Radiology studies showed a 6.4 X 5.9 X 4.1 cm bone lesion diagnostic criteria for asserting malignant transformation of a pleomor-
appearing to arise from the right side of the hard palate involving the phic adenoma (PA).
maxillary alveolus, maxillary sinus, and inferior nasal cavity. There The aim was to determine whether proliferation and expression of cell cycle
was evidence of chronic remodelling of the left middle and inferior molecules (p53, p16, Rb and Cyclin D1) can support the diagnosis of CXPA.
turbinates suggesting a long-standing process. The differential diag- Methods: We performed a multicenter retrospective study including 82
nosis based on radiology included primary bone lesions such as fi- tumours, subdivided into : cell-rich PA (crPA; n=25), multinodular recur-
brous dysplasia and a low-grade cartilaginous neoplasm. Biopsy of rent PA (mrPA; n=20), encapsulated CXPA (eCXPA; n=20) and widely
this tumour showed a predominantly clear cell tumour infiltrating invasive CXPA (wiCXPA; n=17). We analysed the mitotic index/2mm²
bone. Immunohistochemical studies showed positivity for AE1/3, and the proliferation index Ki-67 using an artificial intelligence software
CK7, CK5/6, and negativity for smooth muscle actin, S100, (Machine Learning). These proliferation data were correlated with an
HMB45, PAX8, DOG-1, RCC, and CD10. Subsequent genetic anal- immunohistochemical study on Tissue Microarrays of p53, Rb, p16 and
ysis showed a rearrangement in MAML2 (11q21) gene while Cyclin D1, calculating a H score [0-300].
EWSR1 (22q12) gene was not rearranged. Given the histological, Results: The median Ki-67 in crPA, mrPA, eCXPA, wiCXPA was re-
immunohistochemical and molecular findings, a diagnosis of clear spectively of 2.2% [0,8-6,3], 2.3% [0,35-3,9], 8.1% [2,2-30,3] and 18.4%
cell mucoepidermoid carcinoma was made. [3,6-41,6] (p<0.05).The median mitotic index in crPA, mrPA, eCXPA and
She was treated surgically with maxillectomy and palatectomy. The wiCXPA was respectively 0, 1, 2 and 8 (p<0.05). p53 staining was con-
resected specimen showed low grade clear cell MEC, stage pT4b. sidered of wild type (WT) in all PA, in 64,3% (9/14) of eCXPA, and in
Conclusion: Mucoepidermoid carcinomas can have variable morphol- 30% (3/10) of wiCXPA. The median p16 score in crPAs, mrPAs,
ogies causing a diagnostic challenge, particularly in small biopsy speci- eCXPAs, wiCXPAs was respectively of 30, 35, 70 and 165. The median
mens. The clear cell variant is, as seen in this case, very rare and genetic Cyclin D1 score in crPAs, mrPAs, eCXPAs, wiCXPAs was respectively
analysis is beneficial in these challenging cases. of 20, 15, 25 and 40. Rb was WT in all tumours.
Conclusion: The mitotic and proliferation index in association with ex-
pression of p16, cyclin D1 and p53 could be efficient diagnostic markers
E-PS-11-040 for differentiating Ca ex-AP from AP in litigious cases.
Epithelial-myoepithelial carcinoma - a diagnosis at the breaking point
C. Dahlstedt-Ferreira1, J. Oliveira1
1
Hospital Garcia de Orta, EPE, Portugal E-PS-11-042
A unique case of giant peripheral ossifying fibroma with a focus of
Background & Objectives: Epithelial-myoepithelial carcinoma is a rare Langerhans cell histiocytosis
(< 5% of salivar gland tumours), low-grade, biphasic tumour, associated D. Beypinar1, H. Kacar1, M.F. Acikalin1, D. Arik1, M.î Pinarbasli2, U.
to frequent local recurrence. We report a case of an extremely rare salivar Toprak3
1
gland tumour, which has a very bland histology. Eskisehir Osmangazi University, Department of Pathology, Turkey,
2
Methods: A 94-year-old female presented with a painless mass on the left Eskisehir Osmangazi University, Department of Ear, Nose and Throat,
mandible angle, in 2016, which had grown for a year. She underwent an Turkey, 3 Eskisehir Osmangazi University, Department of Radiology, Turkey
ultrasound and computerized tomography (CT), which revealed a neo-
plastic lesion on her left parotid. The study was proceeded with an aspi- Background & Objectives: Peripheral ossifying fibroma (POF) is a reac-
ration cytology, which showed a benign salivar gland neoplastic lesion tive, non-neoplastic tumour-like growth of the gingiva. POF usually mea-
with myoepithelial differentiation. In 2018 she went to the emergency sure less than 2 cm in diameter, but larger lesions have been rarely reported.
department because of sudden mass enlargement and inflammatory sig- Langerhans cell histiocytosis (LCH) is an uncommon disease involving
nals. She was submitted to a new CT, which confirmed the rapid mass clonal proliferation of Langerhans cells. Here we report an unusual example
 Virchows Arch

of POF reaching a large size. More interestingly and importantly, within the Results: Macroscopicaly the tumour was a well-circumscribed 4.8/3/2.3
lesion, there was a focus of LCH measuring 0.4 cm in diameter. cm, yellow mass with smooth texture and about 0.1 cm thick capsule .
Methods: A 46-year-old female presented with a five-year history of a Microscopic examination revealed a tumour composed of mature adipose
painless, slow-growing mass in the mouth. She has no significant clinical tissue, a thin fibrous capsule but with some peripheral areas with foci of
history. Physical examination showed well circumscribed, approximately glandular parenchyma.
7 cm, vegetative mass on the gingiva. Conclusion: Salivary gland lipomas are rare tumours that can sometimes
Results: A mucosal biopsy was performed, and histopathological find- present with some elements of glandular tissue. The differential diagnosis
ings were consistent with peripheral ossifying fibroma. Radical surgery of has to be made with the adipose replacement of glandular parenchyma
the tumour was performed. Totally 18 slices were sampled from the that manifests in old age or inflammatory conditions associated with
tumour. The microscopic evaluation showed a peripheral ossifying fibro- diabetes mellitus and alcoholism. In this cases there are foci of residual
ma with a 0.4 cm focus of Langerhans cell histiocytosis. residual parotid parenchyma scattered throughout the adipose tissue. In
Conclusion: To the best of our knowledge, this case represents the first our case the parotid acinar tissue was evident only along the periphery
case of LCH occurring within the POF. This case showed the importance without any of the clinical signs mentioned previously.
of extensive sampling in large sized masses to identify concurrent lesions.

E-PS-11-045
E-PS-11-043 Salivary acinic cell adenocarcinoma: an epidemiologic study with
PD-L1 expression in head and neck cancer patients from a center in rare histopathological aspects
Colombia A. Faur1, M. Cornianu1, C. Gurban1, S. Bolintineanu1
M. Ramos1, A. Baldion1, D. Suarez1, S. Perdomo1, M. Palau1, A. 1
V. Babes University of Medicine and Pharmacy, Romania
Avello1, A. Hakim1, A. Escallon1, V. Ospina1, P. Bernal1, G. Ucros1, A.
Muñoz1, O. Torres1, P. Rodriguez1 Background & Objectives: Acinic cell adenocarcinoma (ACC) repre-
1
Hospital Universitario Fundacion Santa Fe de Bogota, Colombia sent a malignant salivary neoplasm in which tumour cells demonstrate
serous acinar differentiation. ACC accounts for about 11-17% of the
Background & Objectives: Immunotherapy with PD-L1 inhibitors have primary epithelial malignancies of the salivary glands. In this study were
shown promise improving survival in some solid tumours, their role in reviewed in retrospect all the ACC diagnosed at City Hospital of
Head and Neck Cancer (HNC) is being studied but is not clear. Our Timisoara over a period of 10 years.
objective is to determine PD-L1 expression in a cohort of HNC patients. Methods: The cases were selected from the Pathology Department. We
Methods: PD-L1 expression was evaluated with immunohistochemistry identified 279 cases of salivary gland tumours. The clinicopathological
of tissue microarrays (TMA) from 38 HNC patients of the Hospital data were retrieived from the records. The slides were reevaluated, clas-
Universitario Fundacion Santa Fe de Bogotá from the InterCHANGE sified and discussed.
study. Ventana SP263 and Dako 22C3 antibody assays were used. Results: We found 11 ACC. There was a male predominance (n=6)
Positivity for PD-L1 expression was calculated using the Combine with the majority of ACC occuring in the parotid gland (n=9) and
Proportion Score (CPS), scores of ≥1 were considered positive. in patients between 61-80 years-old (n=8). The tumours had cyto-
Results: plasmic positive granules for periodic acid-Schiff and alcian-blue
stains. The ACC showed a variable growth pattern: sheets of solid
tumour cells, microcystic growth pattern, papillary-cystic growth
PD-L1 POSITIVITY
VENTANA DAKO 22C3 REPORTED IN
patterns and areas with undifferentiated carcinoma. One case
SP263 LITERATURE showed a unique aspect and had brown pigment granuls in the
cytoplasm that were positive for Fontana-Masson silver impregna-
n % n % %
tion stain and HMB-45 antibody.
ORAL CAVITY (n=20) 19 95 18 90 51-71
Conclusion: ACC represented in our study only a small number of
OROPHARYNX HPV + (n=13) 12 92,3 10 76,9 49-87 patients (n=11) with salivary gland neoplasms. HMB-45 positive
OROPHARYNX HPV - (n=1) 1 100 1 100 29-61 granules were previously described in in periductal and periacinar
LARYNX (n=4) 4 100 3 75 64-66 fibrous salivary tissue in small groups. Until now in salivary gland
tumours studies in with such granules were described they were
found in 2 adenoid cystic carcinomas, and melanocytes were found
Conclusion: PD-L1 expression varied according to the antibody used. in 4 mucoepidermoid carcinoma and one pleomorphic adenoma but
Our data showed a high rate of PD-L1 expression in all locations of HNC in none of the salivary ACC.
irrespectively of HPV status. Further studies should be done to standard-
ize the measurement of PD-L1 expression, type of clone and clinical
significance for HNC. E-PS-11-046
Primary adenocarcinoma of the nasal cavity and paranasal sinuses: a
retrospective study of 6 cases
E-PS-11-044 S. Ben Khalifa1, R. Hadhri1, M. Njima1, A. Bellalah1, N. Ben Abdeljelil1,
Salivary gland lipoma: a rare entity A. Zakhama1, L. Njim1
A. Faur1, S. Bolintineanu1, A. Sisu1, L. Grigorita1 1
Pathology Department of Fattouma Bourguiba Hospital, Monastir, Tunisia
1
V. Babes University of Medicine and Pharmacy, Romania
Background & Objectives: Malignant sinonasal tract tumours comprise
Background & Objectives: Lipomas of the salivary glands comprise <1% of all neoplasms and about 3% of those of the upper aerodigestive
between 0.5% -1.2% of neoplasms of the parotid gland. We present a tract. Primary sinonasal adenocarcinomas (SNA) represent 15% of these
case report of a lipoma of the parotid gland to further characterise its gross malignancies.
and microscopic appearance. Methods: We retrospectively analysed the clinical and pathologic data of
Methods: A 59-year-old man presented to the Oro-Maxillo-facial Surgery 6 patients, diagnosed with SNA in the department of pathology of
Department, City Hospital of Timisoara, with a left parotid painless mass. A Fattouma Bourguiba hospital from 2008 to 2018.The size, location and
resection of the mass with tumour-free margins was performed. histological type of the tumours were analysed.
Virchows Arch

Results: There were 5 men and 1 woman with a mean age of 45 years (22- gestation – 2 cases, 22 weeks’ gestation – 3 cases, 24 weeks’ gestation – 3
60years). Unilateral nasal obstruction, epistaxis and rhinorrhea were the most cases). Fragments from cephalic extremities and/or mandibles were proc-
common symptoms. The average tumour size was 2,6 cm (1 to 5 cm). The essed for light microscopy and immunohistochemistry, by using anti-
tumour was located at the nasal cavity in three cases, at the ethmoidal sinus in Cyclin D1. Cyclin D1 expression was semi-quantitatively assessed, based
two cases and at maxillary sinus in one case. SNAs were of non-intestinal on the intensity of staining and percentage of positive cells.
type in 66,6% of cases(n=4) and of intestinal type in 33,3% of cases(n=2). Results: Cyclin D1 revealed a different expression in epithelial and mes-
Conclusion: Among primitive SNA the 2017 WHO classification distin- enchymal components of the tooth germs, without differences between
guishes two main categories: intestinal type adenocarcinoma (ITAC) and the germs corresponding to incisors, canine, and molars. In early and late
non-intestinal adenocarcinoma (NITAC), entities with different clinical cap stage, we noted a strong nuclear Cyclin D1 expression in all epithelial
and epidemiological characteristics. ITACs may occur sporadically or as structures of the enamel organ, and a moderate one in the mesenchymal/
an occupational-related disease, especially in cases of wood dust expo- ectomesenchymal cells of dental papilla. The early bell stage was
sure. This tumour histologically resembles intestinal adenoma or adeno- characterised by a similar pattern of expression, with the highest intensity
carcinoma with an intestinal type profile (CK20+/CK7-/CDX2+/villin+). of immunoreaction in the ameloblasts nuclei. In late bell stage, the ame-
It is locally aggressive with ~50% local recurrence. Locoregional / distant loblasts presented only a cytoplasmic positivity, the reticular, intermediate
metastasis occurs in 10 - 20% cases and 5-year cumulative survival rate is and extern epithelium of the enamel organ being Cyclin D1 negative,
~40%. NITACs are morphologically heterogeneous tumours, mostly with whereas odontoblasts showed a strong nuclear positivity.
glandular or papillary patterns showing a respiratory type phenotype Conclusion: Cyclin D1 is a valuable marker for cell cycle progression; its
(CK20-/CK7+/CDX2-/villin-). Approximately 25% of NITACs recur expression indicates the different functional status of ameloblasts and
and only 6% of patients die of their tumours. odontoblasts during odontogenesis, with results in the completion of
amelogenesis, while dentinogenesis is still progressing.

E-PS-11-048
Respiratory epithelial adenomatoid hamartoma: a retrosprective E-PS-11-050
study of 3 cases Sclerosing variant of mucoepidermoid carcinoma: an indication for
S. Ben Khalifa1, R. Hadhri1, N. Ben Abdeljelil1, M. Njima1, A. Bellalah1, molecular testing
A. Zakhama1, L. Njim1 A. Ali1, D. Kamel1
1 1
Pathology Department of Fattouma Bourguiba Hospital, Monastir, Tunisia Broomfield Hospital, United Kingdom

Background & Objectives: Respiratory epithelial adenomatoid Background & Objectives: Sclerosing variant of mucoepidermoid car-
hamartoma (REAH) is an uncommon lesion of the upper aerodigestive cinoma can be easily misdiagnosed as a benign condition of the salivary
tract first described by Wenig and Heffner in 1995 as prominent glandular gland such as chronic sclerosing sialadenitis, sclerosing polycystic
proliferations lined by ciliated respiratory epithelium originating from the adenosis or polycystic dysgenetic disease. With less than 30 reported
surface epithelium. cases in the literature, it is important to emphasise on the use of genetic
Methods: We report 3 cases of REAH diagnosed in the department of testing in this rare tumour as an essential diagnostic tool.
pathology of Fattouma Bourguiba hospital from 2008 to 2018. Methods: Herein we are presenting a case of this rare variant in a middle-
Results: There were three male patients aged 50, 55 and 60 years old. The aged male patient arising in the parotid gland. Patient underwent a super-
main symptom was nasal obstruction associated in one case with reccurent ficial parotidectomy after inconclusive fine needle aspiration cytology
rhinorrhea. Endoscopic nasal evaluation showed bilateral polypoid lesions result. Grossly, the tumour was firm, white, with slightly irregular outlines
in all cases. Radiologic assessment revealed polypoid lesions in middle and no areas of haemorrhage or necrosis. Histologically, the parotid tissue
meatus, in nasal septum and in the upper nasal cavity. CT scan revealed was replaced by neoplasm composed of variable sized cystically dilated
bilateral opacification of ethmoid sinuses in one case. All patients ducts and some smaller normal looking ducts. These were associated
underwent polypectomy and the tissue was sent for histopathological ex- intervening markedly sclerotic stroma. No perineurial invasion were seen.
amination with a clinical diagnosis of inflammatory polyposis. Microscopic Background tissue showed dense inflammatory cell infiltrate admired
findings revealed bilateral REAH in one patient and sinonasal REAH as- with atrophic salivary gland tissue. Alcian blue special stain identified
sociated with inflammatory nasal polyposis in two patients. rare goblet cells in the duct epithelial lining.
Conclusion: REAH is seen most often in male adults. Clinically the Results: A provisional descriptive report was issued concluding a low-
lesion presents as a polypoid mass, often in one or both nasal cavities. grade salivary gland neoplasm with unusual morphology and differential
While REAH is benign, awareness and recognition of the lesion is im- diagnosis between sclerosing polycystic adenosis and mucoepidermoid
portant because it can be easily confused clinically with more threatening carcinoma. The case was sent for expert opinion where the diagnostic
tumours such as inverted papilloma and sinonasal carcinoma. difficulty was confirmed and molecular testing was thought, and showed
evidence of t(11;19)(q21;p13) resulting in gene fusion of CREB-
regulated transcription coactivator 1 with Mastermind-like gene family
E-PS-11-049 (MAML2) confirming the diagnosis of sclerosing variant of
Similarities and differences of Cyclin D1 expression in tooth germ mucoepidermoid carcinoma.
development Conclusion: This particular variant comprises a diagnostic challenge for
I.D. Caruntu1, S.D. Savinescu2, L. Lozneanu1, R. Balan1, C. Amalinei1, many pathologists due to the deceptively benign-looking epithelial com-
S. Giusca1 ponent of this tumour and lack of convincing infiltrative pattern of
1
"Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania, growth. A high index of suspicion may be required in view of finding
2
County Service of Forensic Medicine Vaslui, Romania of cystically dilated ducts despite the absence of other classic components
of mucoepidermoid carcinoma. Some Tumours may only show rare or no
Background & Objectives: Cyclin D1, a nuclear protein directly in- goblet cells as was shown in our case. Molecular testing for specific
volved in cell growth and differentiation, is scantily explored in tooth translocation linked to mucoepidermoid carcinoma such as genetic testing
development. Consequently, our work aimed to analyse the Cyclin D1 for t(11;19)(q21;p13) which fuses CREB-regulated transcription coacti-
during the tooth germ formation. vator 1 with MAML2 or t(11;15)(q21;q26) translocation resulting in
Methods: The study group included teeth germs from 15 aborted fetuses CRTC3/MAML2 Gene fusion is considered mandatory to confirm the
(10 weeks’ gestation – 3 cases, 14 weeks’ gestation – 3 cases, 18 weeks’ diagnosis.
 Virchows Arch

E-PS-11-051 Background & Objectives: Dendritic cells (DCs) are antigen presenting
Duct papilloma of minor salivary glands: a benign tumour with cells which also detect tumoral antigens. Their significance in tumour
many malignant mimics progression is on debate. Our aim was to investigate the CD1a positive
A. Ali1, C. Waites1 DC count in ovarian serous tumours.
1
Broomfield Hospital, United Kingdom Methods: A total of 96 consecutive ovarian serous tumours were collect-
ed from the archival files of our department between the years of 2007-
Background & Objectives: Sialadenoma Papilliferum (SP) is a rare benign 2013. CD1a-immunohistochemical staining was performed. CD1a posi-
exophytic tumour of minor salivary glands. The incidence of SP is approxi- tive DC count was calculated as the average score of three hotspots
mately 1% of all minor salivary gland tumours. SP is one of the three known counted at high power field (X40).
ductal papillomas described by World Health Organisation (WHO) along Results: The study population was composed of benign serous tumours
with Inverted ductal papilloma and Intraductal Papilloma. Most common site (BST, n=36/96, 40,6%), borderline serous tumours (BRST, n=18/96
of occurrence is the palate (greater than 80%), particularly at junction of the 18,8%) and malign serous tumours (MST, n=39/96, 40.6%). The number
hard and soft palates. Other minor salivary glands sites of involvement in- of CD1a positive DC was between 0 to 47,6 with a mean of score of 6.
clude buccal mucosa, retromolar region, tonsillar pillar, lip, and nasopharynx. CD1a positive DC was classified as low if the score was <6 (n=67/
Methods: This report focuses on a 72-year-old gentleman who was re- 96,70%) and high if the score was >6 (n=29/96, 30%). Tumours with low
ferred urgently to our hospital with multiple painless slow-growing CD1a scores were significantly more common in BST (94.9%, n=37/39) than
verrucous lumps on the inside of his lower lip of 6 months duration which BRST (33%, n=6/18) and MST (61,5%, n=24/39) (p=0.000). The number of
he constantly traumatised during mastication. On examination, he had no MST with high CD1a score (38,5%, n=15/39) was less than BRST with high
obvious cervical lymphadenopathy. Surgical excision was performed. score (66,7%, n=12/18).
Results: Grossly, the cut section of the tumour revealed a well-defined, Conclusion: The proportion of tumours with high CD1a score signifi-
exophytic lesion with papillary structures in the centre. Histologically, it cantly increased from BST to BRST but showed a considerable decline
comprised of a squamo-proliferative lesion with surface papillomatosis from BRST to MST. The preliminary findings of our study suggest that
and ductal proliferations of the minor salivary glands consistent with CD1a positive DCs are destroyed by malignant tumour cells and further
Sialadenoma Papilliferum. studies can shed a light on whether DC vaccines could be used as an
Conclusion: The clinicopathological and morphological characteristics additional treatment in MST.
of this rare tumour are discussed and our approach to narrowing the
differential diagnoses which include mucoepidermoid carcinoma, papil-
lary cystadenoma and verrucous carcinoma is detailed. E-PS-11-055
Metastasis of renal cell carcinoma to the thyroid gland: a case report
and review of the literature
E-PS-11-052 A. Dhaoui1, Z. Nfikha1, K. Hamza1, D. Ben Ghachem1, K. Bellil1
1
Giant cell tumour of the larynx - a rare entity Forces de Securite Interieure, Tunisia
T. Oğuzsoy1, I.s. ısgor2, l. cinel2
1
Marmara University Training and Researching Hospital, Turkey, Background & Objectives: Renal Cell Carcinoma (RCC) is the most
2
Marmara University Faculty of Medicine, Turkey frequent malignant neoplasm of the kidney. It is well-known for its pro-
pensity to metastasize to unusual sites, and late metastasis, even after
Background & Objectives: Giant cell tumours (GCT) are typically several years, is common. Metastases to the thyroid gland are rare. In a
found at the ends (epiphysis) of long bones. GCT of the larynx is a rare clinical series, up to 1-3% of the oncologic thyroidectomies were due to
entity. Most of GCT of larynx located at thyroid cartilage. thyroid metastases and the most frequent metastasizing tumour was RCC,
Methods: A 35-year-old male was admitted to hospital with progressive followed by lung and breast cancer.
hoarseness and a growing neck mass for the past 2 months. He had no Methods: A fifty-seven-year-old female patient presented with a single
abnormalities in blood tests (including serum calcium). CT imagining and palpable EU-TIRADS5 left thyroid nodule. She has a past medical
showed a 4 cm diameter destructive mass in right ala of the thyroid history of right clear cell RCC diagnosed in 2014 and treated with left
cartilage. The patient referred to FNA. radical nephrectomy in our Institution.
Results: Cytopathologic analysis showed abundant multinucleated Results: Final histological examination showed a clear cell neoplasm positive
osteoclast-like giant cells and oval shaped scattered cells on the back- for PAX8, CD10 and CK7. TTF1 stain was negative excluding a parathyroid
ground. The patient underwent a supra-cricoid laryngectomy. parenchym. Thyroglobulin was negative exluding primitive carcinoma of
Grossly, the lesion was expansive, white to tan colored, un-encapsulated, thyroid gland and calcitonin was negative excluding medullary carcinoma.
4.5 cm diameter, located to the thyroid cartilage. Histologically the tumour Conclusion: A thyroid nodule in a patient with a history of renal malig-
showed an expansive - infiltrative growth pattern. Histopathologic findings nancy should be considered as potentially metastatic. Clinical manifestation
revealed numerous multinucleated osteoclast- like giant cells within a cellular, and radiographic findings are nonspecific. Histological examination and
oval shaped, mononuclear stromal cells. The nuclei of giant cells were similar immunochimestry may be able to distinguish between primary and second-
to stromal cells. The mitotic activity of the mononuclear cells was 1/10 HPF, ary thyroid neoplasms. Despite being a sign of poor prognosis, diagnosis
but there was no atypical mitosis. and surgical intervention are crucial and may increase the survival.
Conclusion: GCT of the head and neck are usually benign but they can be
transformed into malignant GCT or can be primary de novo malignant
GCT. GCT of the larynx is a rare entity and Giant cell granuloma, Brown E-PS-11-056
Tumour, Osteoblastoma and Chondroblastoma should be considered in Evaluation of p16 immunohistochemistry expression in squamous
differential diagnosis. cell carcinoma of the upper aerodigestive tract
J. Kini1, S. Nazareth1, S. Krishnaraj1, S. Sreeram1, H. Kini1, P. Suresh1
1
Department Of Pathology, Kasturba Medical College, Mangalore,
E-PS-11-054 Manipal Academy of Higher Education, Manipal, Karnataka, India
Low-grade sinonasal sarcoma with neural and myogenic features: a
case report Background & Objectives: Immunohistochemistry serves as a tool to
S. Yonat1, O. Erdem1, A. Ozdemir1 detect overexpression of p16 and can be used as a surrogate marker for the
1
Gazi University Medical Faculty Pathology Department, Turkey detection of HPV 16. Though oral squamous cell carcinoma is common in
Virchows Arch

older individuals, non-keratinizing basaloid oropharynx squamous cell car- Methods: We present a 64 year old male patient who had a painless
cinoma caused by HPV was most commonly found in younger age group of swelling in preauricular region. Patient recieved partial parotidectomy
patients. Most of head and neck squamous cell carcinoma have been caused elsewhere with the diagnosis of malignant mesencyhmal tumour, NOS.
by high risk HPV in 5%-75% of the population studied. Recent studies have Patient applied to our center with recurrent swelling in the same location
shown that oropharyngeal carcinomas (88%) caused by HPV were more and underwent total parotidectomy with left sided neck dissection.
common than non-oropharyngeal carcinomas and their incidence rates have Results: Pathologic examination revealed a nodular, hypocellular
been increasing in both genders though there is a males predominance.p16 tumour with myxoid background and infiltrative margins within
immunohistochemistry is used to detect oral and oropharyngeal carcinomas parotid gland. The tumour cells were spindle shaped with scanty
instead of HPV PCR as it is simple and feasible to perform. p16 IHC is cost- eosinophilic cytoplasm and had hyperchromatic, mildly pleomor-
effective and hence should be included in histopathology reports. p16 im- phic nuclei. There were apparent curvilineer vessels, where the
munohistochemistry can be used as strong survival predictor and as an aid spindle cells clustered around . 18 mitoses per 10 high power field
for early detection of HPV positive oral and oropharyngeal squamous cell were detected. Necrosis (%5 of tumour) and extensive perineural
carcinoma which can help in better treatment of the patient. invasion was seen. Deep parotid surgical margins were positive.
Methods: A retrospective and prospective cross-sectional study was done. Tumour cells were negative with CD34, smooth muscle actine, des-
The study was conducted in Pathology department of Kasturba Medical min, S100 protein and MUC4 immune stainings. No staining was
College, Mangalore. All histologically confirmed cases of squamous cell detected with AE1/AE3 antibody.
carcinoma and its variants of the upper aero digestive tract were included in Conclusion: Head and neck region is a very rare site for
the study. Histopathological records of Department of Pathology, KMC myxofibrosarcoma. When facing a spindle cell lesion of parotid gland,
Mangalore were reviewed. A total of 198 consecutive histopathology samples mesenchymal tumours other than more common primary salivary gland
received over a period of 18 months were evaluated. The relevant clinical tumours originating from epithelial/myoepithelial cells should be
details were noted from the patient files. Based on the data collected, the study suspected for a correct diagnosis and appropriate treatment.
population data was analysed with respect to age, gender, risk factors, type,
grade and stage. Immunohistochemistry findings and intensity of p16 staining
were correlated with respect to grade, stage and site of the lesion. Sunday, 8 September 2019 – Wednesday, 11 September 2019
Results: In this study, 73 cases of oral, 65 of oro/hypopharngeal, 40 of E-PS-12 | History of Pathology
laryngeal and 20 cases of nasopharyngeal squamous cell carcinomas were
analysed. The age of the patients ranged from 27 to 80 years. The mean age E-PS-12-001
at presentation was found to be 57.26 years. Majority of the cases (n =53, Professor Leonid Iosifovich Aruin - famous Russian scientist,
72.6%) were seen in the age group of above 50 years. There was a marked pathologist-gastroenterologist (29.05.1924-24.01.2018)
male preponderance in our study with a male female ratio of 2.7:1. A. Zubritsky1
It was observed that 49 cases of oral squamous cell carcinoma were positive 1
Moscow, Russia
for p16 immunohistochemistry. Out of the positive cases, 24 cases showed
score 1 positivity, 19 showed score 2 positivity. Six cases showed score 3 Background & Objectives: This work has the aim to collect and sys-
positivity. On analysing the results of p16 staining of oro and hypopharyngeal tematize the biographical information according to the questionnaire pre-
tumours it was found that p16 was positive in 59 cases. Among those found pared by me. Born in Moscow in the family of doctor. Married. Children:
positive,12 had low score, 41 had score 2, and the rest six had score 3. Of the Michael. Graduated from the Higher Naval School of Naval Medical
24 laryngeal cases scored as p16-positive, three were strongly positive, 13 Academy (1947); PhD thesis on "Changes in adrenal cortex in rheuma-
moderately positive and eight demonstrated only weak positivity. Nine cases tism (clinical, morphological and histochemical study)" (1965), Doctoral
of nasopharyngeal were scored as p16-positive, out of which, three were – on "Pathomorphology of stomach and small intestine in postresection
strongly positive and two demonstrated only faint positivity. Only those with syndromes" (1971).
score 2 and 3 were considered as positive. Methods: Doctor, Pacific and Baltic Fleet, anti-aircraft regiment, Sakhalin
Conclusion: Oropharyngeal and hypopharyngeal squamous cell carcino- Island; Chief, Pathological Department, Naval Hospital, Liepaja; demobilized
mas caused by high risk HPV should be distinguished from non HPV in rank of Lieutenant-Colonel in connection with the reduction of army;
squamous cell carcinomas because it is clinically relevant. As p16 is up- Head, Pathology Laboratory, Research Institute of Gastroenterology.
regulated in oropharyngeal and hypopharyngeal squamous cell carcino- 1/80 words
mas, p16 immunohistochemistry could be used as surrogate marker. P16 Results: Retirement and moving to permanent residence in Israel to their
immunohistochemistry is cheap, simple and easy to perform alternative to children and grandchildren (1995). For the first time intratissue regulators
HPV-PCR and fluorescent in situ hybridization testing which is relatively of regeneration of gastric mucosa were detected – the keylons, and dif-
expensive. atient files. Based on the data collected, the study population ferences in their activity in gastric ulcer were established; he developed
data was analysed with respect to age, gender, risk factors, type, grade and methods of differential diagnosis of chronic liver diseases and described
stage. Immunohistochemistry findings and intensity of p16 staining were their morphological features; initiator of creation of Russian group for
correlated with respect to grade, stage and site of the lesion. study of Helicobacter pylori.Laureate of many nominal awards.Research
interests: Clinical and functional morphology of digestive system.
Undergraduate Student research project funded by Indian Council for Conclusion: Author of over 200 scientific works, including many
Medical Research and partly by Manipal Academy of Higher monographs.Distinctive feature: Kindness, responsiveness, tireless re-
Education, Manipal as undergraduate student research project. searcher, gift of diagnostic heuristics, ability to easily and clearly talk about
fundamental problems of medicine. Hobby: Internet, liked to communicate
with colleagues on Skype. He died at age of 93 from lung edema and was
E-PS-11-057 buried in cemetery of Beit Shemesh, located 23 km from Jerusalem.
Primary myxofibrosarcoma of parotid gland
S.Y. Ercetin1, B. Keskin1, H.K. Turkoz1
1
Marmara University, Turkey E-PS-12-002
George Vladimirovich Shor - Russian pathologist, scientist and edu-
Background & Objectives: Myxofibrosarcoma commonly arises in the cator (23.04.1872-18.07.1948)
limbs of. Head and neck location is quite rare and primary parotid disease A. Zubritsky1
has been reported only twice previously. 1
Moscow, Russia
 Virchows Arch

Background & Objectives: This work has the purpose to collect and Background & Objectives: To collect and systematize the biographical
systematize the biographical data for Professor G.V.Shor in accordance with data according to the questionnaire prepared by me. Born in village Ivitsy
the questionnaire I have developed. Born in St. Petersburg in family of of Odoevsky district of Tula region. Graduated from Moscow Veterinary
postal official. Married. Spouse: Bogen-Shor (Petkovich) Olga Academy named after K.I. Skryabin with distinction, All-Union Legal
Konstantinovna . Graduated from the gymnasium and the St. Petersburg Correspondence Institute (1954) and postgraduate studies at Moscow
Military Medical Academy with honors (1895); doctoral thesis on "Primary Veterinary Academy.
cancer of bronchi, lungs and pleura in relation to pathology" (1903). Methods: Defense of thesis on theme “Pathomorphological changes of
Methods: Pathologist in different hospitals of St. Petersburg; Head, cardiovascular system in high-yielding cows under metabolic disorders”,
Department of Pathology, 1st Leningrad Medical Institute; one of the foun- doctoral – on “Pathomorphology and some issues of pathogenesis of
ders of thanatology; Honored worker of science of the USSR (1933); gastrointestinal diseases in newborn calves”. Professor, Pathology
Chairman of the officer of the Court of honor during naval service. Department with course of forensic veterinary medicine, Moscow
Results: Founded the first experimental laboratory for research on cancer; Veterinary Academy named after K.I.Skryabin, etc. Academician-
one of founders of Leningrad Society of Pathologists; proposed in autop- Secretary, Department of Veterinary Medicine. For the first time in our
sy method of full evisceration of internal organs and a comprehensive country the systems of veterinary-prophylactic measures of reception for
study without the disturbance of anatomical relations, the method for lambs-gnotobiotes are developed and on this model experimental coli-
preservation of anatomical preparations, which consists in pre- bacteriosis is studied.
conditioning liquid of Shor followed by putting them in hermetically Results: Development of complex and fundamental research on study of
sealed vessels simultaneously with creation of archive macropreparations etiology and pathogenesis in development of diagnostic methods and
("Museum of Shor"), method of carrying out clinical-anatomic mapping measures to control leukemia of cattle; much has been done for develop-
and introduced residency for future pathologists. ment of gnotobiology, the use of its methods in solving problems of
Conclusion: Research interests: Problems of thanatology, oncology, pathol- veterinary medicine. Awarded the Gold Medal named K.I.Skryabin for
ogy equipment, etc. Author of over 70 scientific works, including main work successful work on problem of pathology of farm animals (1985), etc.
"On human death, introduction to thanatology". Distinctive trait: Man of Conclusion: Author of more than 300 scientific works, including 23
crystal purity and honesty.Died in Leningrad on the 77th year of life from books and brochures, 15 copyright certificates and patents for in-
cardiovascular insufficiency due to obesity heart. Buried in Leningrad. ventions. Member of Board of All-Union Scientific Society of
H a e m a t o l o g y a n d O n c o l o g y, o f C o m m i t t e e o f Wo r l d
VeterinaryAssociation for Cattle Diseases (1974). Distinctive fea-
E-PS-12-003 ture: Diligence, organizational skills. Died on January 7, 2001 in
Questionnaire portrait of the well-known Russian forensic medical Moscow on 74th year of life.
expert and pathologist Professor Mikhail Ivanovich Avdeev
(16.11.1901-15.03.1978)
A. Zubritsky1 E-PS-12-005
1
Moscow, Russia The role of the federal state autonomous educational institution of
higher education ”Belgorod State University” in the history of the
Background & Objectives: This work has the goal to collect and sys- development of paediatric pathomorphology
tematize the biographical information according to questionnaire pre- T. Pavlova1, V. Kulikovskiy1, L. Pavlova1, A. Nesterov1
1
pared by me. Born in Vyazma, Smolensk Province in the family of an Belgorod State University, Russia
employee. Graduated from the medical faculty of Moscow State
University and full-time postgraduate study at the Department of Background & Objectives: The exploration of historical aspects of path-
Forensic Medicine; defense of doctoral thesis on the topic "Pathological ological anatomy of diseases of children, fetus and newborn allows to
anatomy and pathogenesis of myocardial fragmentation". establish ways of its further development.
Methods: Military service: regimental physician, participated in battles for Methods: Work with archive materials, monographs and textbooks
the elimination of basmachism in Turkestan;Head, Department of Forensic Results: The first book of pathological anatomy was issued in 1826. The
Medicine, 1st MMI named after I.M.Sechenov;Senior Researcher, Institute first chair of pathological anatomy in Russian Empire was founded in 1845,
of State and Law, USSR, etc. Organized a system of forensic institutions and the independent chair in Moscow was founded in 1859. The actual questions
developed instructions to determine the severity of injuries. of obstetric, inflectional and somatic pathology are considered (V. Zinserling
Results: During the Great Patriotic War took part in the work of the State (St. Petersburg), A. Milovanov (Moscow). The children’s prosectorium in
Commission to investigate the atrocities of Nazi invaders in the USSR; Belgorod was founded in 1989. It became one of the educational bases for
various rewards. Research interests: Anatomical pathology of sudden death, students of medical institute (T.Pavlova, the head of the chair) .
questions of the degree of severity of bodily injuries, forensic medical ex- Conclusion: The research of pathological anatomy of diseases of children,
amination in cases of self-mutilation, forensic traumatology, organization of fetus and newborn promotes to formation of scientific knowledge as well as
forensic medical service, etc. Author of more than 100 scientific works, to correct diagnosis for preservation of health and vital activity of human.
including many textbooks, manuals, practical guides and monographs.
Conclusion: Chairman of the Board of Moscow and Deputy Chairman of
the All-Union Scientific Society of forensic doctors, etc. Distinctive fea- E-PS-12-006
ture: Inherent high sense of humor, did not like negligent and dishonest 170 years at the head of Russian Anatomic Pathology (devoted to the
people. Hobbies: Loved theater and even took part in various amateur 170 years anniversary of Anatomic Pathology Department named
performances; had a beautiful voice, sang well. Died in Moscow on the after academician A.I. Strukov First Moscow State Medical
77th year of his life. University named after I.M. Sechenov)
E. Kogan1, V. Paukov1, T. Demura1, D. Protsenko1
1
First Moscow State Medical University (Sechenov University), Russia
E-PS-12-004
Vladimir Petrovich Shishkov - outstanding Russian veterinary pa- Background & Objectives: To show 170 years history of anatomic
thologist, scientist and educator (24.05.1927-07.01.2001) pathology department in First Moscow State Medical University named
A. Zubritsky1 after IM Sechenov in Russia.
1
Moscow, Russia Methods: Analyses of literature and historical data.
Virchows Arch

Results: The first departments of were opened in Russia simultaneously Methods: Diagnostic methods are constantly being improved, and the
in 1845 in Kiev (University of St. Vladimir) and in 1849 in Moscow scope of the concept of biopsy is expanding, which leads to the appear-
(Moscow State University). In 1848 Alexey Ivanovich Polunin - 29- ance of clarifying definitions in the term. Thus, different types of biopsy
year-old educated doctor who graduated in Europe and knew 5 languages are distinguished according to such semantic characteristics as the volume
- became the chair of the department of anatomic and physiologic pathol- of material, method toolkit for obtaining material, type of accuracy con-
ogy. A.I. Polunin appreciated the importance of the views of R. Virchow trol, organ from which biopsy is taken. All of the listed compound terms
and his microscopic method for studying pathological processes. He cre- contain systemic semes of the term biopsy and are included in the notion
ated a museum of grosses, that was initiated by the collection of bones, of biopsy on the principle of hyponyms - a hyperonym.
brought to Russia by Kh.I.Loder. The scientific school of the Anatomical Results: Diagnostic methods are constantly being improved, and the
Pathology Department in Sechenov University has history of 170 years. scope of the concept of biopsy is expanding, which leads to the appear-
Department was headed by famous Russian pathologists: A.I. Polunin ance of clarifying definitions in the term. Thus, different types of biopsy
(1849-1869) , I.F. Klein (1869-1898), I.M.Nikiforov (1898-1916), V.I. are distinguished according to such semantic characteristics as the volume
Kedrovsky (1916-1918), A.I.Abrikosov (1918-1953), A.I.Strukov of material, method, toolkit for obtaining materia, type of accuracy con-
(1953-1972), V.V.Serov (1972-1990), Paltsev M.A. (1990–2009), VS trol. Moreover, all of the listed compound terms contain systemic semes
Paukov (2009-2016) and Kogan EA (2016 - present). In 2015 the depart- of the term biopsy and are included in the notion of biopsy on the prin-
ment was named in the honor of academician A.I.Strukov. ciple of hyponyms - a hyperonym.
Conclusion: The level of scientific methods and technologies advance- Conclusion: The meaning of the word biopsy is significantly modified in
ment on the Department resulted in anatomic pathology scientific school the terminological combination liquid biopsy. At the same time, the actual
development in Russia, which is based on the following postulate: clinical use of the term in modern media actualizes the semantic components of
anatomy, functional morphology, immunomorphology, molecular pathol- the term liquid biopsy, which are common with the concept of traditional
ogy, digital pathology, pathology of stem cells and their niches. biopsy, which can be explained by advertising purposes.

Sunday, 8 September 2019 – Wednesday, 11 September 2019

E-PS-12-007
E-PS-13 | Infectious Diseases Pathology
A brief history of the atomic level studies on human pathologies and
personal perspectives based on the summary of results of the first
pan-cancer 'in vivo' interdisciplinary clinical-scale analysis E-PS-13-003
K. Taran1 A case of human cutaneous protothecosis: another addition to the
1
Medical University of Lodz, Poland literature from United Kingdom
M. Elgoweini1, A. Bal1, S. Allen1, M. Strick2, A. Waters1
1
Background & Objectives: Mass spectrometry (MS) is awarded the four University Hospital Crosshouse, NHS Ayrshire & Arran, United
Nobel Prizes analytical method. Isotope Ratio Mass Spectrometry (IRMS) Kingdom, 2 Glasgow Royal Infirmary, NHS Greater Glasgow & Clyde,
is the most precisely and currently highly developing MS type which alights United Kingdom
an previously unknown atomic level of pathological tissue biology.
Although IRMS studies for medical purposes are considerably scars they Background & Objectives: Protothecosis is a rare algae infection which
open a new window on human pathology. Recently IRMS was showed to primarily affects immunocompromised patients. We present a case of
be applicable to the direct cancer tissue evaluation and its use has allowed to cutaneous protothecosis in an immunocompetent individual with diag-
discover a new area of biomarkers and potential targeted therapies nostic and treatment challenges.
Methods: Interdisciplinary analysis of an isotope effect referred to isoto- Methods: A 67year old diabetic female, who regularly visited
pic fractionation in highly selected human 'in vivo' pan-cancers tissues Mexico, presented with a lump on her upper back initially thought
with the use of IRMS incorporating a search for the relation to the to be a sebaceous cyst. Shortly after excision, a 1 cm papulopustular
established histological prognostic parameters. eruption appeared in the region. Skin biopsy showed central ulcer-
Results: Isotopic profile of cancer tissues with the significant break- ation and extensive inflammation with prominent eosinophils and
throughs at a key moment of cancer cell spread was revealed. Nitrogen histiocytes. Spherical periodic acid-schiff positive organisms, up to
enrichment was identified as a new isotopic hallmark of cancer and the 15 μm in diameter, with occasional morula-like appearance charac-
relation of isotopic fractionation to the established prognostic parameter, teristic of prototheca species were identified. Prototheca
especially of the light microscope type was confirmed as an universal rule. wickerhamii was confirmed on tissue culture and by PCR.
Conclusion: IRMS opens a new age of an atomic level research on Results: The patient was commenced on oral itraconazole and flu-
human pathologies. This extremely modern method does not compete conazole without success. The lesion increased in size with devel-
with microscopic or molecular assessment, contrary it may act as their opment of discrete papules within an area of approximately 7 x
valuable complement especially dedicated to personalised medicine and 4cm in spite of azole therapies. The patient was then commenced
targeted therapies for cancer patients. Complete understanding of frac- on (IV) Amphotericin B. However, the treatment had to be aborted
tionation processes in cancer tissue and available benefits of IRMS use due to underlying renal impairment. The lesion was surgically ex-
requires integration of data by overcoming interdisciplinary barriers. cised with a 1cm margin. She is currently under regular follow up
with no early recurrence.
Conclusion: Cutaneous protothecosis is a rare infection with no specific
E-PS-12-008 clinical features. The diagnosis relies on recognition of characteristic histo-
Is fluid biopsy a biopsy: vocabulary and usage pathological features in conjunction with microbiological confirmation.
S. Mozgovoi1, E. Abrosimova2, A. Kononov1 Management is highly challenging and requires a multidisciplinary approach.
1
Omsk State Medical University, Russia, 2 Omsk State Agrarian
University, Russia
Background & Objectives: The term, on the one hand, has gnoseological E-PS-13-004
and heuristic functions, because it makes it possible to discover and name Isolated pulmonary cryptococcosis confused with lung tumour
new concepts, and on the other hand, it forms and systematizes knowledge, C. Fumagalli1, E. Chenu1, C. Berengua Pereira1, F. Sánchez-Reus1, R.
ensuring their continuity from generation to generation. Consider from this Orellana1, L. López-Villaró1
point of view a relatively new medical term - liquid biopsy. 1
Hospital de la Santa Creu i Sant Pau, Spain
 Virchows Arch

5
Background & Objectives: Cryptococcosis is an opportunistic infection Service de Pathologie, CHU Dijon, France, 6 Plateforme de Gènètique
in immunosuppressed patients that usually presents as des Cancers solides et des Hèmopathies malignes, CHU Dijon, France,
7
meningoencefalitis, while pulmonary disease is less frequently reported. Unitè d'innovation en Gènètique et Epigènètique des cancers, CHU
Transplanted patients are a risk group due to the immunosuppressive Dijon, France, 8 UMR PAM A 02.102 Procèdès Alimentaires et
therapy used to maintain the function of the transplanted allografts. Microbiologiques, Universitè de Bourgogne Franche-Comtè/AgroSup
Moreover, in this group, the incidence of malignancy increases due to Dijon, France
the immunosuppression, so that it’s occasionally difficult to distinguish
between an infection and a malignancy when facing with a mass. Background & Objectives: Child death from rotavirus infection remains
Methods: Herein we report a case of isolated pulmonary cryptococcosis 3 exceptional in developed countries. Although diarrhea, dehydration and
years after kidney transplantation that was clinically misdiagnosed as a lung delayed care are the main causes of decease, other physiopathologic
tumour. A 35yo male received a kidney transplant for end-stage kidney mechanisms consecutive to viremia in relation to human blood group
disease when he was 32yo. During a routine control, a hypermetabolic mass antigens (HBGA) may play a role in some fatal outcomes. Our objective
was found in the middle lobe of the right lung. Due to radiologic findings, was to assess the replication and binding sites in the case of a 16 month-
immunosuppressive therapy and the fact that the patient was a smoker, the old boy which suffered from severe G1P[8] rotavirus acute gastro-
mass was highly suspicious for malignancy and a lobectomy was performed. enteritis with a fatal outcome.
Results: Macroscopically, a 1,7cm lesion with central necrosis was found. Methods: Multiple organ sections from a fatal case of septic shock
The microscopic study showed multiples granulomas with histiocytes and and organ failure linked to rotavirus acute gastro-enteritis in a 16-mo
spherical fungi positive for periodic-acid-Schiff, Grocott-Gomor and boy, with previous low-birth weight and intra-uterine growth retar-
mucicarmine staining. A part of the specimen was cultured in our microbi- dation, were investigated using molecular biology, immunohisto-
ologic service, confirming the presence of Cryptococcus neoformans. Thus, chemistry and immunofluorescence targeting VP2 and VP6 structural
the diagnosis of isolated pulmonary cryptococcosis was made. and NSP2, NSP4 and NSP5 non-structural rotavirus proteins, and the
Conclusion: In transplanted patients, the presence of a lung mass raises H and Lewis antigens.
the differential diagnosis of an infection or a tumour, leading possibly to Results: Histpathology revealed signs of early acute kidney injury and
misdiagnosis and overtreatment, as occurred in this case, so a careful pulmonary diffuse alveolar damage. Immunodetection showed non-
clinical analysis should be performed. structural and structural rotavirus proteins colocalization within viroplasms
and evidence of rotavirus binding to HBGAs in kidney and lung tissues.
Conclusion: In vitro studies have shown the ability of rotavirus to secrete
E-PS-13-005 IL-6 and IL-8 via its main toxin, the non-structural protein NSP4. This
Rhinosporidiosis: report of a case presenting as urethral polyp study brings new insights into mechanisms underlying extraintestinal
G. Morgantetti1, G.A. Medeiros1, J.G.d.N. Barros2, M.L. Balancin1 rotavirus infection and highlights the relation between rotavirus replica-
1
University of Sao Paulo, Brazil, 2 Laboratório Laborocha Filho, Brazil tion and its abilities to bind to HBGAs in kidney. Further studies will be
required in order to clearly determine the relationship of the rotavirus
Background & Objectives: Rhinosporidiosis is a chronic granuloma- replication in multi-organ failure (i.e. acute kidney injury and diffuse
tous disease caused by Rhinosporidum seeberi infection, a protistan par- alveolar damage). Rotavirus infections remain a major public health issue
asite previously regarded to be a fungus, transmitted through traumatized in France, as vaccinations are still not included in the National immuni-
epithelium, most commonly in upper airways, genitals and rectum. zation schedule. Recent hospital-based studies have shown the impact of
Endemic in Asia, Africa and South America, the infection is acquired rotavirus vaccination in terms of delayed care, burden of disease and
through bathing or working in stagnant water, and is not transmitted morbidity.
between individuals. Treatment is surgical, with complete removal of
the lesion being sufficient in most cases.
Methods: A 69-year-old patient presented to the urology outpatient clinic with E-PS-13-007
a 0,8 cm polypoid lesion protruding from the urethral meatus, with clinical What's in the guts?
suspicion of HPV infection. The patient had no relevant background data. I. Dumitru1, B. Mohamed Amine1, X. Sastre Garau1, A. Boyez1,
Results: The patient underwent excisional biopsy and histopathological exam- N. Talhi1
1
ination revealed multiple thick-walled sporangia in various stages of maturation, CHI Créteil, France
surrounded by mild inflammation (Figures 1 and 2). Gomori-Methanamine
Silver (GMS) stain demonstrated pathogen argirophilia (Figure 3). The histo- Background & Objectives: Nontuberculous mycobacterial infections can
pathological analysis alone was enough to confirm the diagnosis of urethral present as a rare and distinct entity called mycobacterial pseudotumors. M.
rhinosporidiosis. No relapse was detected after one-year follow-up. pseudotumors affect immunosuppressed patients with or without AIDS.
Conclusion: Although rare, rhinosporidiosis should be considered as a Pseudotumor of abdomen is a rare and distinct clinical entity that needs to
differential diagnosis of mucosal polypoid lesions, especially in patients be diagnosed before any surgery. We report a young female who was
coming from endemic regions and with history of exposure to contami- referred to our institution with a primary diagnosis of malignancy.
nated water. Due to the disease´s unique morphological features, histo- Methods: We report the case of a 38-year-old woman, HIV positive, who
pathological examination is sufficient for the diagnosis and no special presented with chronic anaemia. The endoscopic findings described a
stain or ancillary test is necessary. suspicious obstruction of the duodenum and biopsies were obtained from
the region. The pathological examination showed extensive infiltration of
the lamina propria with foamy granular or striated histiocytes (pseudo-
E-PS-13-006 Gaucher cells) disposed singly, in clusters, or diffusely and packed with
Pathology of rotavirus-driven multi-organ failure in infants ‘globi’ of acid-fastbacilli. Special stains were negative for periodic acid-
G. Tarris1, G. Belliot2,3, P. Cailler4, L. Martin5,6,7, A. de Rougemont2,8 Schiff reagent and positive for acid-fast staining (Ziehl-Neelsen stain).
1
Department of Pathology - University Hospital of Dijon, France, Results: Althow we don’t have a culture to certify the diagnosis, the ap-
2
National Reference Centre for Gastroenteritis Viruses, Laboratory of pearance of Whipple-like and the positivity for acid-fast staining (Ziehl-
Virology, University Hospital of Dijon, France, 3 UMR PAM A 02.102 Neelsen stain) we retain the diagnosis of atypical mycobacteria infection.
Procèdès Alimentaires et Microbiologiques, Universitè de Bourgogne Conclusion: The pitfall of the case was represented by the lack of clinical
Franche-Comtè/AgroSup Dijon, France, 4 INSERM LNC UMR 1231, information that are critical to the diagnosis and the Whipple-like infiltration
Equipe GAD, Universitè de Bourgogne Franche-Comtè, Dijon, France, of the lamina propria with foamy granular histiocytes and of course the right
Virchows Arch

interpretation of the special stains. Clinicians and pathologists should be thick posterior segment, rounded and uncoiled, with the intestine and egg-
aware of this unusual manifestation of non-tuberculous mycobacteria which filled uterus. The ellipsoid eggs had bipolar plugs. In the posterior region,
affects immunosuppressed patients in order to avoid unnecessary surgery. there was a thick cuticle with prominent annulations, thin hypodermis and
a layer of somatic muscle cells.
Conclusion: There should be a high degree of suspicion in patients coming
E-PS-13-008 from endemic areas presenting with typical symptoms, as this is a treatable
Rare organ involvements in echinococcal disease disease when properly detected. The diagnosis of this case was made at the
H. Göbel1, A.M. Lentzsch2, K. Richter3, J. Fries1 biopsy. This case report pretends to illustrate the essential role of pathology in
1
Institute for Pathology, University Hospital Cologne, Germany, the diagnosis of intestinal parasites besides the traditional stool specimens.
2
Department of Ophthalmology, University of Cologne, Cologne,
Germany, 3 Department of Urology, University of Cologne, Cologne,
Germany E-PS-13-010
Mycetoma in Portugal
Background & Objectives: About 50-60 new cases of Echinococcosis F. Ramalhosa1, R.C. Oliveira1, G. Fernandes1, J. Fraga1, H. Moreira1,
are reported annually in Germany making it a rare entity with more cases M.A. Cipriano1, M.J. Martins1
1
in the southern part of Germany than in the north. Echinococcus Centro Hospitalar e Universitário de Coimbra, Portugal
granulosus is more prevalent worldwide whereas Echinococcus
multilocularis is found within Europe and the southern part of Background & Objectives: Mycetoma is a chronic tropical inflam-
Germany. Echinococcosis presents as a cystic disease most often involv- matory disease, caused by inoculation of either fungi or filamentous
ing lungs and liver, but it can be found occasionally also in other organs. bacteria. Infection slowly spreads to involve skin, bone and subcuta-
Rarely it is found solely in other localizations without liver and/or lung neous tissue. Is mostly predominant in poor tropical countries, asso-
involvement. We present two cases of cystic lesions in the left kidney and ciated with outdoor work-related activities, rarely found in Europe.
the eye respectively with no other organ involvement. Mycetoma diagnosis is based on clinical presentation: a subcutane-
Methods: Case 1: The 23-year-old man presented with increased flank ous mass, draining sinuses and grain discharge. Further study can be
pain and fever up to 40°C which dropped after antibiotic treatment. The done, as bacteria PCR and culture.
cystic disease was known at that time for 1 year. Due to the symptoms the Methods: A 57 years old man, born in Portugal, without travel records,
decision to perform a complete nephrectomy was made. Standard histol- referred to our Hospital with a clinical history of painful growing tume-
ogy was applied. Case 2: The 5-year-old girl presented with proptosis and faction on his right foot since 2000, despite several courses of antibiotics
downward displacement of her left eye for 2 years. The cystic structure and surgical cleaning treatment. Ultrasound revealed nodular and cystic
could be evaluated by magnetic resonance imaging. The lesion was sur- formations and X-ray and MRI showed chronic osteomyelitis with the
gically removed and also examined by standard histology. destruction of deep structures and bone.
Results: Microbiological examinations could not find vital organisms in Results: Specimens obtained through needle aspiration, from the subcu-
the fluid harvested at the time of the kidney operation. In both cases the taneous tissue, were sent to the pathology department, which histologi-
specimens showed a cystic disease involving the kidney and the eye re- cally revealed suppurative granulomas surrounding grains. Periodic-acid-
spectively. Histologically the typical cuticula were found as well as scolices. Schiff and Grocott-Gomori silver staining confirmed the fungi aetiology.
Conclusion: Renal or ocular involvement are rare occurrences in Particularly, in this case, both PCR and culture were negative.
echinococcal disease, which is even more extraordinary, when a solitary Conclusion: Despite the typical clinical presentation, the diagnosis and man-
involvement without the typical lung and/or liver disease is present. agement were delayed because Mycetoma is rare in Portugal. The treatment
We present here two cases of renal and ocular echinococcosis in young depends on the causative organisms: a combination of antibiotics and anti-
people who neither showed other locations of echinococcal cysts. To our fungal agents. In the advanced state of the infectious process, amputation may
knowledge the patients had no recurrent echinococcal involvement. Both be the only available treatment. In our case, the patient has foot deformity and
patients came from countries outside of Germany which may indicate one loss of function, therefore an above-knee amputation was proposed.
should have this differential diagnosis in mind if confronted with cystic
diseases in unusual areas.
E-PS-13-011
Rhino-orbital Mucormycosis in renal transplant recipient: a case
E-PS-13-009 report
Trichuris Trichiura: the importance of histopathology in the A. Ok Atilgan1, E. Yilmaz Akcay1
1
diagnosis Baskent University Faculty of Medicine Pathology Departmant, Turkey
F. Galante Pereira1, C.A. Padrão1, A.M.G. Pereira1, R.S.S. Oliveira1, J.P.
Garcia1 Background & Objectives: Mucormycosis is an invasive fungal infec-
1
Hospital Prof. Doutor Fernando Fonseca, EPE, Portugal tion which is primarily caused by filamentous fungi belonging to the
Background & Objectives: Trichuris trichiura, commonly referred to as a Mucoraceae family and is frequently seen in diabetic and immunocom-
human whipworm, is endemic in tropical and subtropical countries, but a few promised patients. Mucormycosis is categorized as rhinocerebral, pulmo-
sporadic cases have occurred in nonendemic areas. Most infections are light nary, cutaneous, gastrointestinal or disseminated, depending on organ
and tend to be asymptomatic. The diagnosis is made by identifying Trichuris involvement; the most common form is rhinocerebral (39%).1 This form
trichiura eggs in stool specimens; few reports have described detection of the may be divided into subtypes based on which tissues are affected:
parasite in a biopsy specimen. The purpose of this case report is to increase rhinonasal, rhinoorbital or rhinoorbitocerebral.
awareness of this uncommon, but treatable parasite. Methods: We report a case of 28-year-old female who had renal transplan-
Methods: A 54-year-old man, African descendent, with history of mul- tation from a cadaveric donor with vesicoureteral reflux etiology 4 years ago.
tifactorial anemia, asymptomatic, was submitted to a cecum biopsy on Her immunosuppressive regimen was tacrolimus, mycophenolate mofetil.
colonoscopy for iron deficiency anemia after a negative fecal occult blood Results: She presented with complaints of swelling of the right eye. On
test. Hematoxylin-eosin stain was performed. ophthalmologic examination proptosis, ptosis and lateral gaze limitation
Results: Histologically it was identified an adult female whipworm, were observed in the right eye. Orbital magnetic resonance imaging
Trichuris trichiura in an intestinal mucosa sample. It was composed by (MRI) without contrast revealed widespread inflammatory changes in
two distinct body regions: a slender, thread-like anterior segment, and a right optic nerve, medial rectus, retroorbital area and extending to right
 Virchows Arch

paranasal sinuses. Biopsy taken from right sinonasal mucosa and histo- Conclusion: Visceral leishmaniasis with colon involvement is an infre-
pathological diagnosis was mucormycosis than exenteration was per- quent event. The possibility should be raised in patients with immuno-
formed on the right eye. Histopathological examination revealed Mucor compromised status, providing an early diagnosis with correct treatment.
organisms invading orbital connective, neural tissue, bone and mucosal
tissue adjacent to areas of necrosis. Typical hyphae forms are broad with
irregular, thin, nonparallel cell walls lacking septae. She was treated with E-PS-13-014
systemic liposomal amphotericin B and local irrigation and followed Mucormycosis of the maxillary sinus complicated by osteitis: a case
without disease for 25 months. report
Conclusion: Mucormycosis should be suspected in all immunosup- E. Ben Hadj Khalifa1, S. Chaieb1, A. Bdioui1, A. Baccouche1, S. Ben
pressed patients who present with persistent upper respiratory, ocular Khlifa1, M. Mokni2
1
symptoms and not explained by other causes. Cytology and Pathology Department CHU Farhat Hached, Sousse-
Tunisia, 2 Department Of Pathology, University Farhat Hached
Hospital, Tunisia
E-PS-13-012
A case of lethal angioinvasive fungal infection of the kidney in a Background & Objectives: Mucormycosis is a rare opportunistic my-
critically ill patient cosis infection. The responsible agent is a filamentous fungus in the order
C. Masaoutis1, S. Pantelakos 1, D. Sampaziotis1 , A. Sykaras1, F. of the Mucorales, which are ubiquitous, saprophytes of the soil and many
Dolkiras1, C. Vourlakou1 plants. It may be responsible of different clinical pictures. The rhino-
1
Department of Pathology, Evangelismos General Hospital, Athens, orbito-cerebral form is the most common clinical form in the literature.
Greece We present a case of mucormycosis of the maxillary sinus complicated by
osteitis. In this observation we will illustrate the clinical, radiological and
Background & Objectives: Fungal infections of the kidney are rare and pathological aspects of this infection.
encountered primarily in immunocompromised patients. Candida, Methods: We report the case of a 49-year-old woman who consulted for
Aspergillus and Mucor are the most common causative microorganisms. purulent rhinorrhea and a pain of the right maxillary sinus evolving for 21 days.
We present a case of a 74-year old male burn victim of the 2018 Attica Results: A 49-year-old woman without any pathological history admitted
wildfires, hospitalized in our ICU for sepsis, who developed acute renal for right maxillary sinusitis evolving for 3 weeks. The radiologic exams
injury with imaging findings consistent with kidney infarction. Left ne- showed a right maxillary sinusitis complicated by diffuse maxillary oste-
phrectomy was performed. itis. A sinus biopsy was performed bringing back 3 fragments of inflam-
Methods: We received a 152gr kidney measuring 12x8x5.2cm, diffusely matory and suppurative necrotic material containing spores and branched,
pale, with an indistinct corticomedullary junction and numerous parietal septate mycotic filaments positive for PAS and Grocott staining. Then,
thrombi in branches of the renal artery. Multiple sections were examined the diagnosis of mucormycosis was made. The evolution was favourable
by light microscopy and histochemistry. after surgical cleaning and the use of high-dose amphotericin B
Results: Microscopy revealed extensive coagulative necrosis of the kid- Conclusion: The fungi and spores of Mucorales show minimal pathoge-
ney consistent with infarction with areas of intraparenchymal haemor- nicity toward normal persons, they can initiate aggressive infections un-
rhage. Many blood vessels were thrombosed. After meticulous examina- der clinical conditions responsible for decreased immunity.
tion of the necrotic tissue in H&E sections, branching and somewhat
variable in width hyaline fungal hyphae were noted within the wall or
the lumina of arterial branches. The hyphae were highlighted with the use E-PS-13-015
of histochemical stains PAS and Grocott. The fungus, isolated from an Hydatid disease: two soft tissue cases and 20-year review in our
intraoperatively obtained thrombus of the renal artery, was identified as center
Fusarium in culture. M. Trujillo Coronado1, B. Tristan Martin1, M. Arguelles Pintos1, L.
Conclusion: These findings are consistent with an angioinvasive Lopez Brasal1, P. Ramos Ponton1, F.J. Pinedo Moraleda1
1
hyalohyphomycosis of the kidney. Fusarium spp. represent an uncommon Hospital Universitario Fundacion Alcorcon, Spain
cause of such infections. Despite antifungal treatment, the patient's condition
continued to deteriorate and he died on the 30th day after nephrectomy. Background & Objectives: Hydatid disease (HD) is a helminthic zoo-
This case points out the possibility of a fungal infection in renal infarcts of nosis caused by tapeworm Echinococcus granulosus larvae. It presents a
immunocompromised / critically ill patients. These infections, unless worldwide distribution, being endemic to the Mediterranean area,
treated early, progress rapidly and have a high mortality rate. Australia and South America.
After ingesting contaminated food, oncospheres are released in the human
E-PS-13-013 small bowel, passing through the mucosa and entering the portal system,
Visceral leishmania - a rare event with hepatic involvement (75%), or reaching the systemic circulation,
R. Caetano Oliveira1, P. Carreira2, H. Garcia2 hypothetically through lymphatic/venous bypasses, with lung (15%) or
1
Pathology Department, CHUC, Coimbra, Portugal, 2 CEDAP, Portugal splenic (8%) involvement. Primary soft tissue HD is very rare.
Methods: Two primary soft tissue HD cases have been diagnosed in our
Background & Objectives: Leishmaniasis is a disease cause by a para- hospital: 59-year-old male, with a 2 cm-gluteal lesion with progressive
site – Leishmania, endemic in some parts of the World, namely in growth for years; 69 year-old male, with a 20 cm-thigh mass in the vastus
Mediterranean countries. The most common form in visceral leishmani- lateralis muscle.
asis, especially with liver and bone marrow involvement, more frequent Results: In the first case, the subcutaneous lesion was excised, revealing a
in patients with immunodeficiency. Colon involvement is rare, with 2 cm-cyst, formed by a fibrous pericyst, laminated layer and proligerous
scarce case reports in the literature. membranes, and protoscolicex.
We describe a rare case of colonic leishmaniasis. In the second case, radiology ruled out hepatic or pulmonary involve-
Methods: Male patient, HIV positive, with 60 years old and complains of ment, and positive serologies for E. granulosus were obtained. After 6
diarrhea. Colonoscopy showed no mucosal alterations. Biopsies were taken. months of treatment with albendazole, with serological negativization but
Results: Biopsies showed diffuse histiocytic population, between the colon lesion stability, percutaneous drainage was performed, sending 15 ml of
glands, with multiple small and oval organisms with bar shaped paranuclear pasty and yellowish fluid, where laminated membrane debris and degen-
kinetoplast, positive for Giemsa and negative for silver stainings. erate (probably parasitary) fragments were identified.
Virchows Arch

We reviewed our database from 1997 to 2019 for HD, finding 20 cases, immunosuppression is supposed to be the cause. We evaluated IFN-γ
with 14 hepatic lesions, 4 soft-tissue lesions, 1 lesion in sputum, and 1 and IL-10 production in cutaneous lesion of patient with DCL and local-
orally expelled nodule. ized cutaneous leishmaniasis (LCL).
Conclusion: Soft tissue HD should be considered in the differential di- Methods: A case-control study was carried out with 12 patients with
agnosis, even without hepatic or pulmonary involvement. In suspicious LCL and 8 with DCL, matched by age. IFN-γ and IL-10 were labelled
cases, it could be crucial for patient management. by immunohistochemistry in skin lesions biopsies. Cytokines quantifica-
tions were performed manually using ImageJ software in 10 captured
microsections (400X) per lesion. Relative frequency of the cytokine pro-
E-PS-13-016 ducing cells was calculated.
Atypical localisation of cryptococcosis as the reason for exitus letalis Results: Seven (87.5%) patients with DCL were males and 1 (12.5%)
Y. Korneva1, R. Ukrainets2 female and all with LCL were males. There was no significant difference
1
Smolensk Regional Institute of Pathology, Russia, 2 Smolensk State between the two groups regarding IFN-γ production by the inflammatory
Medical University, Russia cells infiltrating the lesions, the median of IFN-γ labelled cells was 2.0%
in LCL and 4.6% in DCL (p =0.18). IL-10 production occurred in 1.6%
Background & Objectives: GIT may be affected by opportunistic infec- of inflammatory cells of DCL patients skin biopsies and in 0.4% of the
tions, but very rarely. Most often Oesophagus and colon are affected, but ones with LCL (p = 0.04).
stomach involvement is uncommon and usually found as post-mortem Conclusion: Higher IL-10 production observed in the lesions of patients
finding in cases of dissemination. Cases of cryptococcal affection of with DCL suggests a possible mechanism for the modulation of immu-
stomach are very rarely described in literature, and only few of them nosuppression favoring parasite dissemination.
became the reason to seek medical help.
Methods: 50-year-old patient without an improved immune status died in 40
minutes after admission to the Emergency Hospital due to intensive bleeding E-PS-13-018
form gastrointestinal tract. During autopsy on the lesser curvature a perforat- Morphometric evaluation of paracoccidiomycosis cutaneous depth of
ing defect of stomach wall, penetrating to omentum minor with erosion of infection
vessels and manifestations of profuse bleeding was detected. The case was D. Nunes Oliveira1, V. Holanda Ferreira2, G. Bitu dos Santos Ponte2, P.V.
considered as K25.6 (ICD-10). But histological examination revealed in the Pereira Motoyama2, S. Capelo Barroso Garcia2, S. Andrè de Souza
margins of ulcer as well as stomach wall revealed clusters of round and oval Júnior2, J. Carneiro Melo1, M. Luiz Balancin3
1
cells with optically empty cytoplasm, which have clearly defined contours, Department of Pathology, Postgraduate Program in Public Health,
these formations turn purple on Mouri stain, surrounded by non-specific Faculty of Medicine, University of Fortaleza, Brazil, 2 Faculty of
inflammatory infiltrate. Additionally fungi Candida and Aspergillus in the Medicine, University of Fortaleza, Brazil, 3 Pathology Division, Clinics
superficial layers of defect margins were detected, while Cryptococci in- Hospital, Faculty of Medicine, University of São Paulo, Brazil
volved full thickness of stomach wall. Cryptococcal dissemination also was
seen in heart, lungs, liver, kidneys. Background & Objectives: Paracoccidioidomycosis (PCM) is an infec-
Results: Mycotic etiology of stomach ulcers, as one of the manifestations tion caused by a dimorphic fungus with severe consequences if not diag-
of generalized cryptococcosis, was not diagnosed in a patient during his nosed and treated properly, having the highest mortality rate among sys-
lifetime and became unexpected findings in a postmortem histological temic mycosis. The disease has a slow progression, with peak between 10
examination of the patient's tissues. The formation of mycotic granulomas and 20 years old, however clinic manifestations usually occurs between
in the stomach with further destruction led to acute ulcer formation, com- 30 and 50 years old. The infection is primarily pulmonary, with the skin
plicated by penetration to the omentum minor and involvement of its being involved secondarily, but it may also involve other organs. The
arteries - is an extremely rare clinical observation. Subsequent gastric objective of this study was to analyse the paracoccidioidomycosis' skin
bleeding and hemorrhagic shock were the immediate cause of the pa- slides to determine the depth of the lesions.
tient’s death. Methods: Observational, analytical, cross-sectional study, in which stu-
Conclusion: It is necessary to remember about the possibility of gastro- dents of the University of Fortaleza’s Pathology League analysed 53 skin
intestinal tract affection by opportunistic infections and their specific slides. To this matter, CaseViewer, a digital microscope software, was
morphological picture, especially in patients with immunodeficiency. It utilized to analyse the slides.
is very important for investigation of biopsy specimens from alive pa- Results: After the analysis of the slides, we classified them in four groups
tients, since the verification of mycotic lesion requires additional histo- according to the depth of the lesion. Group 1 included lesions of depth up to
logical stains and layering of inflammatory infiltrate blacks out 1mm, group 2 those between 1mm and up to 2mm depth, group 3 between
Cryptococci, but verification of this etiological agent is essential for cor- 2mm up to 4mm and group 4, lesions with depths greater than 4mm. There
rection of treatment regimen. were 12 lesions (22,64%) classified into group 1, 22 (41,5%) into group 2,
19 (35,8%) into group 3 and no lesions were classified into group 4. The
arithmetic average was 1,70mm and the median was 1,63mm.
E-PS-13-017 Conclusion: We concluded that paracoccidioidomycosis cutaneous lesions
IL-10 modulating immunosuppression in disseminated cutaneous are located preferentially within the epidermis and the dermis. As it is an
leishmaniasis infection that can affect almost every organ, further studies are needed to
L.P. Sousa dos Santos1, A. de Queiroz Sousa1, P.D. Torres Sindeaux Filho1, determine the extension of the lesions in other organs and tissues.
D.I. Magno Cavalcante1, K. Miranda Sá1, M.M. de Lima Pompeu1
1
Federal University of Ceará, Brazil
Sunday, 8 September 2019 – Wednesday, 11 September 2019
Background & Objectives: Disseminated cutaneous leishmaniasis E-PS-14 | IT in Pathology
(DCL) is a rare and emerging disease, mainly caused by Leishmania
(V.) braziliensis. It starts usually as a single ulcerated lesion followed by
E-PS-14-001
hematogenous parasite spread, leading to the appearance of multiple le-
Digital microscopy - is there a need for standardisation?
sions compromising at least two body parts. The lesions are pleomorphic,
S. Schöniger1, G. Bänfer1, R. Diezko1, B. Jasani1
ulcerated, papular, nodular and acneiform. The mechanism of parasite 1
Targos Molecular Pathology GmbH, Germany
spread are not yet well understood and transitory Th1 cells
 Virchows Arch

1
Background & Objectives:Digital and light microscopy are often used Institute of Pathology, School of Medicine, University of Belgrade,
interchangeable for evaluation of tissue specimens. The aim of this study Serbia, 2 Clinic for Dermatology and Venerology, Clinical Center of
was to compare both methods and to highlight major influencing factors. Serbia, 3 Laboratory for Molecular Pathology, Institute of Pathology,
Methods: Comparisons were performed between the 20x magnification School of Medicine, University of Belgrade, Serbia
of Aperio ImageScope on a 3K computer with a screen size of 31 cm
(resolutions: 1920 x 1080, 2560 x 1600, 2048 x 1152, 2736 x 1824; Background & Objectives: Mycosis fungoides (MF) is a primary
screen scaling factors: 200%, 150%, 100%), a Zeiss Axio Scope A1 cutaneous T-cell lymphoma characterised by clonal proliferation
and a Labomed CxL microscope, respectively. of lymphocytes with cytogenetic alterations (e.g. TP53 or
Results: The respective field of view is influenced by the resolution and CDKN2A deletion and c-MYC translocation). Imatinib mesylate
screen scaling factor as well as the microscope and type of 20x objective. In (IM) is a tyrosine kinase inhibitor used for the treatment of leukemia
digital microscopy, a larger field of view corresponds to a lower resolution and gastrointestinal stromal tumour (GIST). Secondary solid or he-
and a higher screen scaling factor. This impacts in particular on the cell matopoietic neoplasms have been described during or several years
count of highly cellular tumours containing small cells. In urothelial cancers after IM treatment. IM treatment induced antinuclear antibodies and
up to 50% differences in cell numbers per 20x visual field were obtained MF-like skin reactions were previously described but true MF has
(100%; 1920 x 1080 or 2736 x 1824). In comparison to the rectangular not been reported yet.
computer screen, the microscope has circular field of view. This disparity Methods: Histological, immunohistochemical, and genetic characteris-
influences the evaluation of lateral aspects of identical tissue areas. tics assessed by fluorescent in situ hybridization (FISH) were analysed in
Conclusion: This study emphasizes the need for standardization for light skin lesions.
and digital microscopy. Variations in size and shape of the field of view Results: We present a case of a 51-year-old woman treated with IM
can have an impact on the cell count and tissue evaluation and therefore due to GIST. Three months after the IM initiation non-pruritic ery-
can cause interobserver differences. thematous scaly plaques appeared on face and trunk. Dominant
histopathologic finding was epidermotropic infiltrate of atypical
T-lymphocytes, mostly of CD4+ phenotype with partial loss of
E-PS-14-002 CD5, diffuse loss of CD7 and PD-1, Ki67 positivity in 10% of
Microorganisms in gastrointestinal lesions: educational and collabo- dermal T-lymphocytes. Deletion of CDKN2A was confirmed by
rative software FISH without concomitant c-MYC or TP53 rearrangement.
F. Mundim1, J.B. Assis1, A. Mendonca1, J. Neto1 Altogether these findings suggested an MF development.
1
UNIVAS, Brazil Conclusion: IM causes clonal proliferation of lymphocytes and
secondary non-Hodgkin lymphomas. Loss of T-cell markers and
Background & Objectives: The introduction of technological applica- aberrant molecular findings by FISH can be useful diagnostic tools
tions or collaborative software has become an important alternative in the differentiating true MF from drug-induced skin reactions after IM
search for knowledge optimization, offering high-resolution images treatment.
through mobile devices with unlimited accessibility, but for diagnosis of
gastrointestinal lesions, there is a technical difficulty to find image Bank.
Objective: To construct, validate and register collaborative and education- E-PS-15-002
al software with images and texts referring to microorganisms of gastro- Dietary methyl donors can influence proliferation of human cell lines
intestinal lesions and that will be adapted for mobile devices. in vitro
Methods: Retrospective, observational, transversal, analytical, individual E. Kiss1, Z. Nemeth1, M. Dank1
1
and uncontrolled study. For the construction of collaborative software, Cancer Centre, Semmelweis University, Budapest, Hungary
after eligibility criteria, 11 images from gastrointestinal biopsies reports of
patients, provided by the Laboratory of Pathology of the Clinical Hospital Background & Objectives: DNA methylation has role in gene ex-
Samuel Libânio, Pouso Alegre, Minas Gerais from 2007 to 2016 were pression, cell proliferation or maintenance of DNA integrity.
used. Twenty (20) medical pathologists participated in the study, which Nutrition is an important factor, which considerably influences
evaluated as partially adequate, adequate and totally adequate. the development and progression of cancer. Dietary methyl donors
Results: It was considered as partially adequate, adequate and totally are food components, which provide methyl groups for the one-
adequate in the first validation. In the second validation, through the carbon metabolism supporting methylation processes. Our aim was
use of the Delphi technique, it was considered as appropriate and fully to examine the effect of dietary methyl donors on cell proliferation
adequate. The questions used in the validation of the collaborative soft- on different human cancer cell lines to investigate whether could
ware contributed favorably to the internal consistency of the instrument be used as a potential complementary therapy in cancer treatment.
and its validated content since the respective Cronbach alpha (α) was Methods: Panc-1 and MCF7 cell lines were grown in 96 well plates and
0.8692 and the Global Content Validity Index (IVCg) was 0, 93 in the treated with different concentrations (1x, 10x, 20x) of methyl donors.
first validation and 0.94 in the second validation. Basal concentration (1x) was: 17 mg/L L-methionine, 9 mg/L choline
Conclusion: The collaborative software showed reliability and consisten- chloride, 3 mg/L folic acid and 2 mg/L vitamin B12. Cell proliferation
cy for professionals in the Surgical Pathology practice, which made pos- was measured by absorbance at 490nm after 24, 48 and 72 hours using
sible the construction of the MICROP application in the approach of MTS cell proliferation assay. Two-way Anova and Bonferroni posthoc
microorganisms in gastrointestinal lesions. test was used to compare the absorbance of the treatment groups to the
controls.
Results: Methyl donor treatments caused reduction in the absorbances in
Sunday, 8 September 2019 – Wednesday, 11 September 2019
both observed cell lines. Basal and twenty times higher concentrations
E-PS-15 | Molecular Pathology
caused significant, dose-dependent decrease in the proliferation of Panc-1
cells (p≤0.05 and p≤0.01, respectively) at 48 hours treatment, compared
E-PS-15-001 to the control. In case of MCF7 cells, treatments caused dose-dependent
Mycosis fungoides during imatinib mesylate treatment - true lym- decrease in the proliferation after 48 and 72 hours (p≤0.01 and p<0.001,
phoma or cutaneous drug reaction? respectively).
M. Jovanovic1, M. Milinković Srećković2, D. Milčić2, S. Ćirović3, M. Conclusion: Our results indicate that methyl donor supplementation in-
Denčić Fekete3, M. Nikolić2, M. Bosić1 duces significant decrease in cell proliferation of Panc-1 and MCF7
Virchows Arch

tumour cells as well. Our results suggest that an appropriate dietary guid- Conclusion: RCC with sarcomatoid dedifferentiation is a relatively rare
ance might be an effective complementary treatment for cancer patients but agressive form of RCC, occuring in 5% of all RCC cases.The sarco-
but need further, and more detailed investigation. matous areas in RCC may, in addition to a non-specific spindle cell
morphology, show more specialized lines of differentiation such as
Funding by EFOP-3.6.3-VEKOP-16-2017-00009. osteosarcomatous or leiomyomatous.

E-PS-15-003 E-PS-15-008
A case of large B-cell lymphoma with IRF4 rearrangement in ingui- Molecular classification of bladder tumours: about 40 cases and lit-
nal lymph nodes erature review
C. Masaoutis1, P. Lampropoulou2, D. Rontogianni3 A. Douida1
1
Evaggelismos General Hospital of Athens, Greece, 2 Metaxa Hospital, 1
Department of Pathology, Hassan II University Hospital, Fez, Morocco
Greece, 3 Department of Pathology, Evaggelismos Hospital, Athens, Greece
Background & Objectives: Molecular heterogeneity is a characteristic
Background & Objectives: A 21-year-old male presented with isolated feature of all human cancers. In this study, we established the molecular
bulky left inguinal and iliac lymphadenopathy and massive ipsilateral leg subtype of urothelial bladder cancers and we correlated these molecular
oedema, gradually established over the course of 7 months, without B- subtypes with WHO grade, TNM classification and the clinical evolution.
symptoms, lymphocytosis or organomegaly. Incisional lymph node biop- Methods: We retrospectively reviewed the data of 40 patients who were
sy was performed. diagnosed with bladder cancer in the departments of urology and pathology
Methods: Light microscopy, immunohistochemistry and fluorescent in at the Hassan II university hospital center, over a period of 6 years (2013-
situ hybridization (FISH). 2018). We recorded patients’ age and sexe, the type of sample, the degree of
Results: The biopsy revealed a diffuse, monotonous, medium-sized cell atypia, grade and TNM stage at diagnosis. An immunohistochemical study
population with a small to moderate amount of cytoplasm and homoge- was carried out by the antibodies against CK5/6, CD44, CK20 and P53.
neous chromatin with only occasional, inconspicuous nucleoli. No starry Results: The mean age was 60 years (42-82).The sex ratio=5.6. Trans-
sky pattern was appreciated. The immunophenotype was: CD20[+], urethral resections of the bladder were performed in 85% of cases. The
CD10[-], BCL6[+], MUM1/IRF4[+] uniformly, c-MYC[+] ~50%, diagnosis was made on an operative specimen in 15% of cases. Atypia
BCL2[-] <25%, CD5[-], CD23[-], cyclin-D1[-], CD30[-] with a Ki67 was minimal in 25% of cases, moderate in 22.5% and severe in 52.5% of
index >95%. FISH with break-apart probes revealed a translocation in- cases. A molecular classification was performed for the 40 cases. 52.5%
volving the DUSP22/IRF4 locus and was negative for c-MYC, BCL2 or were classified as basal, 32.5% as luminal and 15% were not classified
BCL6 rearrangements. The patient responded favourably to treatment (10% triple negatives and 5% triple positives). Basal tumours were more
with CHOP. common in women, and were clinically aggressive, characterised by ad-
Conclusion: The large B-cell lymphoma with IRF4 rearrangement is an vanced stage (42.8% were classified in T2 at the time of diagnosis) and
uncommon lymphoma, typically affecting the head and neck lymph metastatic disease at presentation (62,5% of cases).
nodes, the Waldeyer ring or the intestine of children and young adults. Conclusion: The bladder cancer molecular subtypes were associated with
The unusual location, as in this case, reported only once until now, should different prognoses and targeted therapies. If validated in prospective
not deter from testing for IRF4 rearrangements, especially in young pa- studies, molecular subtyping will be integrated into bladder cancer clin-
tients with suggestive morphological and immunophenotypical findings. ical management.

E-PS-15-005 E-PS-15-009
Case presentation: sarcomatoid renal cell carcinoma with MDM2 "Fishing" ALK in urinary bladder: report of two cases of inflamma-
amplification tory myofibroblastic tumour
T. Čugura1, J. Jeruc1 I. Filipovic1, J. Filipovic1, M. Zivotic1, S. Radojevic-Skodric1, S.
1
Institute of Pathology, Ljubljana, Slovenia Cirovic1, M. Bosic1, J. Markovic-Lipkovski1
1
Institute of Pathology, Faculty of Medicine, University of Belgrade,
Background & Objectives: A 66-yeard old male underwent abdom- Serbia
inal surgery due to a large retroperitoneal tumour causing accute
ileus. An intraoperative frozen section of the tumour infiltrating in- Background & Objectives: Inflammatory myofibroblastic tumour
testinal wall showed pleomorphic spindle and epithelioid cells with (IMT) is an intermediate, rarely metastasizing neoplasm of urinary
high mitotic rates and areas of necrosis. The preliminary diagnosis of bladder, consisting predominantly of myofibroblastic spindle cells
a malignant tumour, suspicious of a high-grade sarcoma, was made. and inflammatory cells. Anaplastic lymphoma kinase (ALK) 1
The resected specimen revealed a tumour measuring 23 x 18 cm, immunopositivity is required for the differentiation of IMT from
infiltrating the descending colon, spleen, pancreas and extending into other aggressive spindle cell tumours. In addition, fluorescence in
the hilum of the left kidney. situ hybridization (FISH) is usually used as a confirmation of the
Methods: Considering location, clinical setting and morphology, analysis diagnosis.
of MDM2 amplification by DNA fluorescence in situ hybridization Methods: We evaluated morphology, immunohistochemical (IHC) pro-
(FISH) was performed. Immunohistochemical staining for cytokeratin file and FISH of urinary bladder tumour samples, obtained from two male
AE1/AE3 (CKAE1/AE3), racemase, CD10 was performed. patients. The following antibodies were used: vimentin, CK (AE1/AE3),
Results: The specimen was extensively sampled: most of the sections ALK-1, p16, p53, KI67, HHF35, alfa-SMA, HMWCK, p63, CD34,
showed similar morphology as the frozen section with tumour cells fo- GATA3, desmin, myogenin, and S100. Additionally, ALK gene rear-
cally positive for CKAE1/AE3, racemase and CD10. A minor part of the rangement was determined by FISH analysis.
tumour adjecent to the hilar kidney area showed papillary architecture Results: In both cases, the histopathological examination revealed
morphologically and immunohistochemically consistent with papillary similar morphology. Lamina propria and the muscle were infiltrat-
renal cell carcinoma (RCC). FISH analysis showed MDM2 gene ampli- ed by spindle and polygonal cells arranged in fascicles, accompa-
fication. A final diagnosis of sarcomatoid papillary RCC with nied by an inflammatory infiltrate consisted of plasma cells, lym-
sarcomatoid component showing MDM2 amplification was made. phocytes, neutrophils, and eosinophils, with prominent blood
 Virchows Arch

vessels in the edematous stroma. IHC showed positive staining to Methods: Endometrial cells were fixed and examined at 3 and 14
vimentin, CK (AE1/AE3), ALK-1, p16, p53, KI67, HHF35, and passages. Primary monoclonal antibodies to Lamin B1, CDKN1A,
alpha-SMA, while HMW-CK, p63, CD34, GATA3, desmin, β-galactosidase, ki-67, p53, SIRT-1, SIRT-6 were used for ICC
myogenin, and S100 were negative in both cases. However, the reaction. Alexa Fluor 488 and Alexa Fluor 647 (1:1000, Abcam,
FISH analysis revealed 20% of cells with ALK gene rearrangement UK) were taken as secondary antibodies. Scanning of samples was
in one case, while the other showed an absence of this mutation. performed on a microscope FluoView1000 (Olympus, Japan).
Conclusion: FISH analysis of ALK gene rearrangement in IMTs of Results: All investigated markers were detected in endometrial cul-
the urinary bladder may be variable. Performing FISH alone might ture in all age groups. The lowest level of the relative expression
fail to provide reliable diagnosis. Therefore, when ALK-1 immuno- area of p53 (5,9%) was registered in the cells of 25-30 age group
stain is positive, but FISH fails to confirm ALK gene rearrangement, at 3 passage, while the value of relative expression area of ki-67
the diagnosis of IMT may still be made by an exclusion of other was the highest (15.89%). Statistically significant increase in the
spindle cell neoplasms. relative area of immunopositive staining depending on the age, was
observed in the analysis of the relative expression area of SIRT-1
(r=0.92, p<0.01) and SIRT-6 (r=0.99, p<0.01). The minimum level
E-PS-15-010 of the expression of SIRT-1 (5.25%) and SIRT-6 (6.33%) was ob-
Microsatellite instability evaluation in colorectal cancer cases served at 14 passage of group 35-45 years, the maximum - at 3
Z. Mikola1, Z. Szollosi1, N. Konyhas1 passage in all studied groups.
1
BAZ County Hospital, Hungary Conclusion: The data on the change in the expression of the
molecules characterizing the SASP phenotype were confirmed
Background & Objectives: Current clinical reference methods for eval- with increasing age of the patients, and a number of molecules
uating microsatellite instability are immunohistochemical staining of mis- were also identified that item showed a change in expression in
match repair proteins and/or PCR analysis of frequently mutated repeti- the SASP type cells. We propose the use of new biomarkers that
tive regions of DNA. The fully automated Idylla MSI Assay performs the are capable of assessing biological versus chronological age and
detection of microsatellite instability directly from FFPE human cancer status of female reproductive system.
tissue sections utilizing a PCR reaction followed by high-resolution melt-
ing curve analysis. The main objective of the study was to compare the
reliability of these two methods. E-PS-15-012
Methods: To assess the suitability of the novel marker set to detect Small nuclear RNA (RNU6-1) is a novel susceptibility gene for diffuse
MSI status in colorectal cancer cases, we retrospectively evaluated large B cell lymphoma in Arab descent population: a case-control
MSI status in 20 colorectal cancer FFPE samples This sample set study
included a 50/50 ratio of MSI versus MSS samples evaluated by S. Al-Khatib1, N. Abdo1, L. Al-Eitan1, D. Zahran1
1
immunohistochemical markers for mismatch repair genes MLH2, Jordan University of Science and Technology (JUST), Jordan
MSH2, MSH6, PMS2.
Results: Testing the 10 microsatellite stable cases on the Idylla MSI Background & Objectives: In addition to messenger RNAs, transfer
Assay, it detected no mutation in the 7 novel biomarkers, confirming RNAs, and ribosomal RNAs, a group of regulatory RNAs are identified.
the MSS status. On the contrary, the 10 samples which displayed mis- Those regulatory RNAs are non-coding and form the vast majority of the
match repair gene loss by immunohistochemical markers, the Idylla MSI human genome. Regulatory RNAs sequence is highly preserved found in
Assay detected microsatellite instability (MSI-H) in five cases. both bacteria where they termed as small RNA and in eukaryotic cells
Conclusion: The IdyllaMSI Assay provides a much more reliable meth- where they known as non-coding (nc) RNAs which includes small nuclear
od than the immunohistochemical markers for mismatch repair genes in ribonucleic acid (snRNA) and small nucleolar RNA (snoRNA). The (nc)
order to evaluate MSI-H vs MSS status, the latter demonstrating 100% RNAs or microRNAs found within the splicing regions. They encode no
sensitivity but only 75% specificity. proteins and their primary function is in the processing of pre-messenger
This study on a diverse set of colorectal samples successfully demonstrat- RNA in the nucleus by serving as a catalytic center within the splicesome.
ed the validity of the novel MSI biomarkers to discriminate between MSI- The length of an average snRNA is approximately 150 nucleotides. They
H and MSS status. are transcribed by either RNA polymerase II or RNA polymerase III.
ncRNAs form complexes with one of the ribonucleoproteins (snRNP) as-
sociated proteins. Among the most common snRNA in those complexes are
E-PS-15-011 U1, U2, U4, U5, and U6 splicesomal RNAs. Named according to their
InflammAging: SASP as molecular landscape of cell senescence Uridine content. The U6 snRNA or RNU6-1 is nuclear based belongs to
V. Rodichkina1, I. Kvetnoy1, V. Polyakova1 Lsm-class of snRNA that transcribed by RNA polymerase III and forms the
1
Otts Institute of Obstetrics, Russia non-coding small nuclear RNA (snRNA) component of U6 snRNP. U6
snRNA through its combination with snRNP and U4snRNA forms a large
Background & Objectives: Aging at the cellular and organ levels RNA-protein molecular complex or splicesome, responsible for post-
negatively affects reproductive function. It is proved that immune transcriptional modification of pre-mRNA. A step took place in the nu-
cells play a crucial role in the physiology of the reproductive cleus by excision of the introns from pre-mRNA. The importance U6
system. Inflamaging - associated with aging, chronic and systemic snRNA is emphasized by the presence of many back-up copies of the
inflammatory condition caused by cells acquired SASP phenotype gene and the highly conserved sequence of U6 snRNA across species.
(senescence associated secretory phenotype). In current study we The aim of this study is to analyse the relationship between RNU6-1
reviewed biomolecules characterizing the SASP phenotype (Lamin single nucleotide polymorphism (SNP) rs 6457327 and the overall risk
B1, CDKN1A) and supposed new related markers (SIRT-1, SIRT-6, and prognosis of DLBCL cases in Jordanian Arab population.
p53 and ki-67). Endometrial material in patients without endome- Methods: The study population composed of 125 patients whom diag-
trial pathology (n = 15) was obtained by carrying out a pipe biopsy nosed with DLBCL at KAUH from the period of 2013 to 2018 and 235
to create cell cultures. All patients were of reproductive age (23-45 healthy cancer-free control subjects with similar geographic and ethnic
years) and had normal menstrual cycles. The patients did not re- background to patients. All cases of DLBCL has been diagnosed inde-
ceive hormone therapy (neither GnRH analogues nor danazol or pendently by a hematopathologist according to the 2008 WHO classifi-
COCP). cation of tumours of haematopoietic and lymphoid tissues.
Virchows Arch

4
DNA extraction: Genomic DNA was extracted for the DLBCL Faculty of Medicine of the University of Coimbra, Portugal, Internal
patients from formalin-fixed and paraffin-embedded (FFPE) tissue Medicine, University Hospital Coimbra, Portugal
using commercially available kit, DNeasy Blood & Tissue Kit
(Qiagen Ltd., West Sussex, UK), using the manufacturer’s proto- Background & Objectives: Erdheim-Chester disease (ECD), a rare in-
cols. Genomic DNA from control-subjects blood samples was ex- flammatory disorder with broad non-specific clinical spectrum, is
tracted using the QIAamp® or Promega DNA Mini Kit according characterised by infiltration of organs by CD68+ and S100– cells.
to the manufacture’s instruction. The quality of extracted DNA was Commonly affects bones, kidneys, retroperitoneal space, skin and brain.
examined by agarose gel electrophoresis and ethidium bromide If untreated, progresses rapidly being causing fatal. Although a rare dis-
staining. The concentration and purity of extracted DNA was ease, the number of new cases is increasing and 53 years is median age at
assessed by using NanoDrop 1000® spectrophotometer. The select- diagnosis without gender influence.
ed polymorphisms were analysed within candidate genes using BRAF (V600E) mutation has become a parameter concurrent for the diagnosis.
Sequencing technique (Sequenom® iPLEX assay). RNA extraction Methods: Case report 1: bone biopsy of 68-years-old female with
and real-time quantitative PCR: Total RNA was isolated with PET positive images scattered over large bones, Planar xanthomas
TRIzol reagent (Invitrogen, USA) according to the manufacturer’s were reported in clinical registry. Bone biopsy revealed CD68+ and
instructions. The reverse transcription was performed using S100– cells.Case report 2: pericardial surgical biopsy of a 70-
Tra n sc r i p t o r F i r st S t r a n d c D N A Sy n t h e s i s Ki t ( R o c h e , years-old female with PET positive revealing multisystemic images
Indianapolis, IN). Real-time PCR was performed with SYBR understood as inflammatory process with pancreatic, vascular and
Green PCR Master Mix (Applied Biosystems, Foster City, CA) renal involvement. Positive CD68 and negative S100 cells were
on a Bio-Rad CFX96 real-time PCR system. The RT-PCR condi- identified supporting the diagnosis.
tions were as follows: sufficient denaturing at 95°C for 50 seconds, Results: In both cases due to non-solving clinical status with common
denaturing at 94°C for 50 seconds, annealing at 55°C for 50 sec- treatment, liquid biopsies were performed on IdyllaTM ctBRAF Mutation
onds, elongation at 72°C for 50 seconds (30 cycles) and a final Assay for BRAF codon 600 mutations. BRAF codon 600 mutation was
cycle at 72°C for 10 minutes. β-actin served as the internal posi- observed and allowed vemurafenib prescription.
tive control. The RT-PCR products were examined by gel electro- Conclusion: Molecular analysis of ECD samples has demonstrated the
phoresis. Statistical analysis: All Overall survival (OS) was calcu- prevalence of BRAF (V600E) mutation in more than 50% the cases, and
lated from the date of diagnosis to the date of death or last visit for opened a new area for treatment options with promising results.
those who were alive at the time of final data collection and anal- Two more cases of liquid biopsies of two female of ECD cases, with
ysis. All statistical analyses were performed using IBM SPSS CD68+, S100– cells, allowed identification of BRAF codon 600 muta-
Statistics version 20.0 (SPSS Inc., Chicago, IL, USA). The clinical tions, enlarging the therapeutic possibility, beyond the concurrence for the
characteristics and response rate of the patients were compared diagnosis.
using Chi square tests. Hardy–Weinberg equilibrium Test was esti-
mated by a goodness-of-fit χ2 test. The Kaplan–Meier method was
used to construct survival curves, and results were compared using E-PS-15-014
a log-rank test. The association between polymorphism and the risk EGFR mutation analysis in lung adenocarcinoma in cerebrospinal
for DLBCL was calculated by unconditional logistic regression. fluid and peripheral blood: a case presentation
The survival curves were displayed using GraphPad Prism 6 soft- O. Hurdogan1, M. Sari2, D. Yilmazbayhan1, Y. Ozluk1
1
ware. All significant variables ( Istanbul University, Istanbul Faculty of Medicine, Department of
Results: In this study, 125 DLBCL patients and 238 ethnically and geo- Pathology, Turkey, 2 Istanbul University, Oncology Institute, Division
graphically matched healthy controls were enrolled. Of the patients, of Medical Oncology, Turkey
52.8% were males and 47.2% were females with mean age of 53.7 years
(17 – 89). The mean age for the controls was 43.2 years (6-89) and 38.7% Background & Objectives: This case has been accepted for presentation
were males. Our study showed that the frequency of C and A alleles of the at Molecular Pathology and Trainees SS session. We present a demon-
RNU6-1 SNP 6457327 among patients were 84% and 16%, respectively. strative case representing the use of molecular pathology in precision
additionally, an increased risk of DLBCL associated with RNU6-1 medicine.
rs6457327 C>A in the co-dominant, dominant, and recessive models Methods: EGFR mutation testing was performed with Cobas® EGFR
[odds ratio 2.04, 1.62, and 2.11, respectively; 95% confidence interval Mutation Test v2.
(CI) 1.14-3.64, 0.96-2.73, and 1.18-3.74, respectively; p value=0.021, Results: A 57-year-old female presented with a metastatic lung tumour.
0.067; and 0.0088, respectively]. Kaplan-Meier survival analyses showed Transthoracic needle biopsy showed adenocarcinoma. Mutation analyses
no statistically significant results. for EGFR were reported to be wild-type. After six-cycle course of chemo-
Conclusion: This study is the first to reveal the relationship between therapy her metastases regressed. Two months later masses in the lung and
RNU6-1 rs6457327 gene polymorphism and DLBCL patients, indicating brain progressed. Liver metastases reoccurred after four months and a liver
that RNU6-1 may serve as a novel susceptibility gene for DLBCL pa- biopsy was performed to repeat EGFR mutation analysis. EGFR p.L858R
tients in Jordanian Arab descent population. mutation was detected and patient received EGFR tyrosine kinase inhibitor
(TKI) therapy. After one year of uneventful follow-up, newly-developed
This study is funded by Jordan University of Science and Technology. brain metastases were detected. Cerebrospinal fluid (CSF) cytology re-
Grant #: 2017/225. vealed metastatic carcinoma. Synchronous plasma was also obtained for a
paired EGFR mutation analysis. EGFR p.L858R mutation was detected in
CSF puncture, whereas cfDNA from the plasma was positive for p.T790M
E-PS-15-013 mutation. The treatment was switched to a third generation EGFR TKI. The
Erdheim-Chester BRAF mutation in liquid biopsy - two case reports brain metastases showed complete response and CSF puncture proved to
L. Carvalho1, A. Alarcão1,2,3, A.F. Ladeirinha1,2, M. Reis Silva1,2,3, T. become negative at 5 months.
Ferreira1,2, A.I. Rodrigues1, E. Gaspar4, A. Aparício Martins4, V. Sousa1 Conclusion: We think, this case poses a good example for the feasibility
1
Institute of Anatomical and Molecular Pathology, Faculty of Medicine of small amounts of cytological samples in mutation analyses and guid-
of the University of Coimbra, Coimbra, Portugal, 2 CIMAGO - Research ance of treatment. This case also shows how EGFR mutation status may
Center for Environment, Genetics and Oncobiology, Faculty of Medicine, differ in synchronous plasma and CSF samples and emphasizes the com-
University of Coimbra, Coimbra, Portugal, 3 Centre of Pulmonology, plementarity of both techniques.
 Virchows Arch

E-PS-15-016 compound entrectinib in patients with solid tumours harboring TRK/

Cell stress and apoptosis associated biomarker expression correlates ROS1/ALK gene fusions was initiated. The aim of the study was to iden-
with triple-negative breast cancer prognosis tify the TRK, ROS1, ALK other rare gene fusions in patients treated in
Á. Nagy1, T. Krenacs1 single institution.
1
1st Department of Pathology and Experimental Cancer Research, Methods: FFPE and cytological specimens from 1121 patients were en-
Semmelweis University, Hungary rolled to the study. For FFPE samples 2-step diagnostic test was per-
formed: (I) the IHC screening using a pan-receptor tyrosine kinase cock-
Background & Objectives: Breast cancer, including its triple negative tail of antibodies targeting TRK/ROS1/ALK proteins, (II) an RNA-based
subtype (TNBC) is heterogeneous. TNBC shows the worse outcome anchored multiplex-PCR next generation sequencing (NGS) assay in IHC
despite novel treatment options. Here, we studied the prognostic rele- positive specimens. In case of cytological specimens and FFPE samples
vance of cell stress and apoptosis related biomarker expression for reveal- with limited tissue, IHC was omitted and NGS was performed directly.
ing clinically relevant subgroups within TNBC. Results: The 480/1121 specimens were positive after IHC. In 34 (3%)
Methods: 59 primary cases of CK5 positive (basal-like) TNBC were samples gene fusions were detected and characterised.
immunostained for cell stress (hsp70, calreticulin, HMGB1) and apopto- Conclusion: The two-step IHC/NGS testing approach is an effective
sis (p53, AIF1, bcl-2, cytochrome C, cleaved-caspase-3 and caspase-8) strategy to identify patient populations with gene fusions, enabling dis-
related biomarkers in tissue microarrays and marker expression was cor- crimination of active fusions and identification of novel ones.
related with disease outcome. Survival analysis was also performed in
silico based on Affimetrix mRNA expression databases mined with the
KM-potter (http://kmplot.com) software. E-PS-15-018
Results: In TNBC, in silico mRNA data allowed to correlate biomarker Expression analysis of HH network in histological subtypes of germ
levels with recurrence-free survival (RFS), while in situ protein data could cell tumours in children
be linked to OS (overall survival) and PFS (progression-free survival). E. Iżycka-Świeszewska1, D. Kuleszo1, B. Lipska-Zietkiewicz1, K.
Cleaved-caspase-3 and caspase-8, and AIF1 levels showed positive cor- Czarnota1, W. Grajkowska2, G. Drabik3, J. Stefanowicz1, E. Drozynska1
1
relation with RFS, OS and PFS at mRNA and protein level. Calreticulin, Medical University of Gdansk, Poland, 2 Institute Memorial Childs
bcl2 and HMGB1 mRNA expression significantly correlated with OS, Health Center Warsaw, Poland, 3 Iagiellonian University Krakow, CM,
but did not reach significance at protein level, while hsp70 protein (but Poland
not mRNA) production was inversely associated with OS and PFS.
Spearman-rank analysis showed significant positive correlations of Background & Objectives: Germ cell tumours (GCTs) are a group of
cleaved/activated caspase-3 expression with those of cleaved-caspase-8, neoplasms with different levels and directions of differentiation.
cytochrome C, AIF1 and calreticulin. Several signaling pathways participate in migration and specification
Conclusion: Our results suggest that potential activation of the en- of germ cell line in embryogenesis, including Sonic Hedgehog (SHH)
doplasmic reticulum stress, as well as the extrinsic and intrinsic pathway. The abnormal function of this signaling is observed in
caspase-dependent apoptosis, and the AIF1 mediated caspase- many type of cancer- gastric, lung, breast, pancreatic, prostate, and
independent cell death pathways may reflect a better disease out- medulloblastoma. The role of SHH signaling in GCTs has not been
come in TNBC. analysed in detail.
Methods: 30 cases of tumours of different histological categories of
This work was supported by NVKP_16-1-2016-0004 and GINOP-2.3.2- paediatric GCTs (mature teratoma, immature teratoma, mixed GCT,
15-2016-00020 grants of NKFIH. yolk sac tumour, dysgerminoma/seminoma, embryonal carcinoma)
and control tissues were studied for expression of SHH pathway
related genes. Paraffin-embedded tissue sections underwent DNA
E-PS-15-017 and RNA isolation. Expression analysis was performed with 3 re-
Next generation sequencing in TRK/ROS1/ALK and other rare genes peats qPCR in each case with Quiagen kits (Hedgehog Signaling
fusions detection - a single institution experience from clinical trail Pathway RT2 Profiler PCR Array) including 84 genes engaged in
A. Tysarowski1, K. Seliga2, M. Wagrodzki3, A. Szumera-Cieckiewicz1, SHH signal transduction. The next step was analysis with dedicated
A. Gos2, R. Zub2, M. Kotarska-Puerto4, M. Krzakowski5, J.A. Siedlecki2, software Geneglobe (Qiagen).
M. Prochorec-Sobieszek3 Results: The significant differences in expression between control and
1
Department of Pathology and Laboratory Medicine, The Maria tumour samples were observed concerning some key genes: SMO, GLI1,
Skłodowska-Curie Memorial Cancer Center and Institute of Oncology HHIP, GLI3. In addition, PTCHD1, ERBB4, FGFR3, WNT3, FGF9,
Warsaw, Poland, 2 Molecular And Translational Oncology, The Maria ZIC1, ZIC2, LRP2, and WIF1 were overexpressed in different tumours.
Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Some significant differences in expression between various GCTs histo-
Warsaw, Poland, 3 Department of Pathology, The Maria Skłodowska- logical categories were also found.
Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Conclusion: Performed analysis showed that some SHH pathway- relat-
Poland, 4 Ignyta, Inc., San Diego, CA, USA, Poland, 5 3Department of ed proteins are involved in GCTs biology in context of level and direction
Lung Cancer and Chest Tumour, The Maria Skłodowska-Curie Memorial of differentiation. Expression of some related genes is lowered than in
Cancer Center and Institute of Oncology, Warsaw, Poland normal tissue.
Work financed by Polish National Science Centre grant 2014/15/B/NZ4/
Background & Objectives: Patients with solid tumours harboring TRK/ 04855 (head: E. Iżycka-Świeszewska).
ROS1/ALK or other rare gene fusions account for <3% of cancer popula-
tion; however, those fusions have been seen in over 40 different tumour
types, including gastrointestinal, lung, head & neck, and sarcoma. Phase E-PS-15-019
1 studies of entrectinib reported a 79% Overall Rate of Response across A rapid and customisable NGS library preparation for down to 0.1%
multiple histology types in patients with gene fusions who were naive to allele frequency mutation detection
inhibitors of these targets, received an efficacious dose, and had extracra- F. Hernandez-Guzman1, X. Peng1, G. Luo1, K. Park1, A. Kraltcheva1, B.
nial disease. A potentially registration-enabling Phase 2 global basket trial Ding1, A. Hatch1, Y. Fu1, V. Mozhayskiy1, C. Van Loy1, J. Kilzer1, M.
(The STARTRK-2:Studies of Tumor Alterations Responsive to Targeting Andersen1
1
Receptor Kinases) of the investigational tyrosine kinase inhibitor Thermo Fisher Scientific, USA
Virchows Arch

Background & Objectives: Multiple research applications require

Sunday, 8 September 2019 – Wednesday, 11 September 2019
high sensitivity for mutation detection which is beyond the error
E-PS-16 | Nephropathology
rate of commonly available Next Generation Sequencing (NGS)
platforms. For example, “liquid biopsy”, which scans blood sam-
ples for low frequency tumour derived DNA, has been described E-PS-16-001
as a promising early cancer detection tool with the potential for IgA nephropathy with Human-Deficiency-Virus (HIV) infection:
improved survival rates for various cancers such as colon, breast case reports with immunohistological study
and skin. M. Otani1, T. Tsuji2, K. Ono3, N. Uesugi4, N. Kato5, T. Inoue5, E.
Methods: Our recently launched Ion AmpliSeq™ HD technology Ashikaga5, S. Iwasaki5
1
enables down to 0.1% Limit of Detection (LOD) from cell free Division of Diagnostic Pathology, Yokohama City University Medical
DNA (cfDNA). In combination with Ion AmpliSeq™ HD Library Center, Japan, 2 Department of Pathology, Sapporo City Hospital, Japan,
3
Kit, custom Ion AmpliSeq™ HD panels and Ion GeneStudio™ S5 Department of Pathology, Yokohama Municipal Citizen's Hospital,
sequencing system, Ion AmpliSeq HD technology enables detection Japan, 4 Department of Pathology, Fukuoka University Faculty of
of low level variants from various sample types. The libraries can Medicine, Japan, 5 Department of Nephrology, Yokohama Municipal
be prepared in as little as 3 hours. Control DNA and RNA samples Citizen's Hospital, Japan
were used for evaluation with 20 ng input.
Results: An Ion AmpliSeq Oncology Panel and the equivalent Ion Background & Objectives: Renal diseases associated with HIV infec-
AmpliSeq HD panel were evaluated using control DNA with tion include acute renal failure, chronic kidney disease, and renal side
known variants present at 5%, 1%, 0.5% and 0.1% frequencies. effects of therapy. IgA nephropathy occurs as one of the HIV-associated
Both Ion AmpliSeq and Ion AmpliSeq HD panels performed well immune-mediated glomerulopathies. We encountered two cases of IgA
with the higher (5%) variant frequency samples. Only Ion nephropathy in patients with HIV infection, and examined their renal
AmpliSeq HD retained the high sensitivity and specificity for biopsy specimens for the presence of HIV and property of IgA in the
low frequency variant calls. Additionally, we have successfully immune-complexes (ICs).
detected copy number variation and fusions. Methods: The first case is a 51-year-old man with HIV infection who had
Conclusion: Ion AmpliSeq™ HD technology combined with anal- been under anti-HIV therapy for 20 years. Proteinuria was first noted 10
ysis with Ion GeneStudio™ S5 system enables fast detection of years after the initial HIV infection. Gradually, the urinary protein excre-
low-level variants from liquid biopsy and other samples with 0.1% tion increased up to 3+, with occult urinary blood. The second case is a
limit of detection. 25-year-old man, who was detected to have urinary protein and blood at
the diagnosis of HIV infection. The serum level of IgA was increased.
Results: Renal biopsy was done in both cases. The first case revealed
E-PS-15-020 mesangial cell hypercellularity and prominent infiltration of lymphocytes
Development of an NGS solution for targeted and immune check- in glomeruli. IgA, IgG and C3 were positive. Paramesangial and
point therapies subendothelial electron-dense deposits (EDD) were noted. The second
V. Mittal1, S. El-Difrawy1, D. Cyanam1, P. Williams1, N. Khazanov1, E. case showed mild mesangial hypercellularity. IgA, IgG, IgM was positve,
Wong-Ho1, C. Van Loy1, S. Sadis1 and paramesanbial EDDs were identified. Immunohistologically, the
1
Thermo Fisher Scientific, USA staining for galactose-deficient (Gd)- IgA1 was positive, but, HIV protein
antibodies were not detected in both cases.
Background & Objectives: Next-generation sequencing (NGS) is Conclusion: In Japan, IgA nephropathy is most common in patients with
used to support routine clinical research in oncology. However, HIV infection. It has been reported that the ICs contain HIV-specific IgA
the advent of cancer immunotherapies requires that clinical re- antibody and HIV protein antigen. However, we could not find HIV
search solutions must also address biomarkers for immune check- protein antibodies in both cases. They were almost the same as common
point inhibitors including tumour mutational burden (TMB) and IgA nephropathy, even if the disease was caused by HIV infection.
microsatellite instability (MSI). Therefore, we developed an NGS
solution appropriate for FFPE tissues that addresses biomarkers
for targeted and immune checkpoint therapies. E-PS-16-002
Methods: Gene content was selected based on prioritization of Lyme-associated membranous nephropathy. A case report and re-
actionability and variant prevalence of biomarkers in solid tu- view of literature
mours. The assay uses Ion AmpliSeq™ technology with manual M. Wagrowska-Danilewicz1, Z. Zbrog2, M. Bonczysta3, O. Stasikowska-
or automated library preparation, automated templating on the Ion Kanicka1, M. Danilewicz3
1
Chef™, and sequencing on the Ion Torrent GeneStudio™ S5 Nephropathology Department, Medical University of Lodz, Poland,
2
sequencing platform. An automated variant calling workflow is Mikolaj Copernik Hospital in Lodz, Poland, 3 Pathology Department,
provided within Ion Reporter. Streamlined access to clinical de- Medical University of Lodz, Poland
cision support software is enabled by Oncomine Reporter.
Results: Over 400 genes with known DNA based alterations and Background & Objectives: In approximately 20% of cases in adults,
over 50 RNA fusion drivers are included. A coding sequence foot- membranous nephropathy is secondary to various disorders, including
print to support TMB was generated and microsatellite regions are infection, systemic disease, drugs, and malignancy. Lyme disease is a
included to support MSI. In preliminary development studies, the chronic, multi-systemic, inflammatory disorder of humans and animals
assay displayed good uniformity and consistent read depth to sup- associated with infection by the tick-borne spirochaete, Borrelia
port robust variant calling. In-silico assessment of TMB using burgdorferi. Kidneys are not typically involved in the disease. The liter-
publicly available whole-exome cancer sequencing data resulted ature is scant regarding renal involvement of Lyme disease in humans.
in high correlation (R2 > 0.90, 0-40 mut/mb). MSI detection was Methods: We present a 40 years-old-male with a past medical his-
concordant with results from on-market MSI assays. tory of arthritis developing after a tick bite. He did not get early
Conclusion: A comprehensive NGS assay was developed to support treatment. On the basis of clinical manifestation and serological
routine clinical research in oncology that includes endpoints for TMB tests a late stage of Lyme disease was diagnosed. Since January
and MSI. More detailed information on the assay and an update on per- 2018 the patient received doxycycline, rovamycine and tynidazole.
formance will be presented. Since September 2018 he observed a crural oedema. Finally,
 Virchows Arch

patient was admitted to Nephrology Department with massive cru- Results: We Present a case of a 42-year-old female who presented
ral oedema and nephrotic syndrome without renal insufficiency. with nephrotic-range proteinuria and preserved renal function.
Kidney biopsy was preformed Immunology screen was negative. Renal biopsy showed evidence
Results: Light microscopy, immunofluorescence study and electron mi- of a membranoproliferative glomerulonephritis with mesangial
croscopy examination revealed membranous glomerulonephritis. matrix expansion and double contours formation.
Conclusion: In conclusion, this case indicates that secondary causes of Immunohistochemistry for IgG, IgA, C3d and C1q was positive.
membranous glomerulonephritis include infection of Borrelia Electron microscopy showed masses of atypical collagen fibrils with-
burgdorferi. This association presumably results from immune complex in the mesangial and the subendothelial areas of the glomeruli. Based
injury to the glomeruli caused by bacterial antigens. on these findings a diagnosis of collagenofibrotic glomerulopathy
was made.
Supported by Grant of Medical University of Lodz. Conclusion: Collangiofibrotic glomerulopathy is a rare diagnosis in
which immunoglobulins and complements are not usually detected.
This is however the second such case with a "full-house" pattern of
E-PS-16-003 staining, possibly reflecting entrapment of proteins within the accumulat-
Primer Hyperoxaluria in a 4 month boy: a case report ed collagen fibrils. This highlights the importance of performing routine
S. Aydin Mungan1, E.B. Ozdogan2, A. Ahmetoglu3, E. Cakir1, T. electron microscopy in native renal biopsies to avoid misdiagnosing such
Bulduk4 cases as lupus nephritis.
1
Karadeniz Technical University, School of Medicine Pathology
Department, Turkey, 2 Karadeniz Technical University, School of
Medicine, Department of Paediatric Nephrology, Turkey, 3 Karadeniz E-PS-16-005
Technical University, School of Medicine, Radiology Department, Interstitial nephritis and membranoproliferative glomerulonephritis
Turkey, 4 Karadeniz Technical University, School of Medicine, Pediatry in primary Sjögren syndrome: a report of 2 cases
Department, Turkey V. Almeida1, C. Faria2, R. Nogueira2, C. Pardinhas2, N. Oliveira2, A.
Belmira2, R. Alves2,3, V. Sousa1
1
Background & Objectives: Primary hyperoxcaluria (PH) is caused by a Institute of Anatomical and Molecular Pathology, Faculty of Medicine
deficiency of the liver peroxisomal enzyme alanine: glyoxylate- of the University of Coimbra, Coimbra, Portugal, 2 Centro Hospitalar e
aminotransferase (AGT), which catalyzes glyoxylate to glycine. When Universitário de Coimbra, Portugal, 3 Faculdade de Medicina da
AGT activity is absent, glyoxylate is converted to oxalate that accumulate Universidade de Coimbra, Portugal
in the kidney and other organs. People with PH are at risk for recurrent
nephrolithiasis, nephrocalcinosis, end stage renal disease. We report a 4 Background & Objectives: Sjögren syndrome is a rare progressive au-
month old boy with hyperoxaluria who was brought to the pediatry clinic toimmune exocrinopathy, affecting primarily the lacrimal and salivary
with diarrhea. He also had high levels of creatinin (2,5 mg/dl). glands. Renal involvement is frequent, being interstitial nephritis the most
Methods: Renal biopsy was performed bacause of high levels of common histopathologic diagnosis. Glomerulonephritis, an unusual man-
creatinin and suspicious radiological findings. Rutin sections were eval- ifestation, is generally associated with mixed cryoglobulinemia. The fol-
uated by H&E, histochemical reactions and polarised light microscopy. lowing cases illustrate the complexity and diversity of findings on
Results: Renal biopsy had 12 glomeruli, and their morphological find- Sjögren syndrome.
ings were consonant with the patient's age. In the interstisium almost all Methods: A 59-years-old man (Case 1) and an a 50-years-old woman
tubulary lumens were filled with a light-grayish material. This material (Case 2) with primary Sjögren syndrome were referred to the Nephrology
had birefrigence under polarised light microscope but could not be seen department due to nephrotic range proteinuria. Both patients had low C3
with light microscope. These materials called oxalate crystals. levels. HBV and HCV antibodies and HIV were negative.
Radiological and clinical findings also supported the diagnosis of renal Cryoglobulinemia was negative. Serum protein electrophoresis showed
oxalosis or hyperoxaluria. no spike. Renal biopsy was decided.
Conclusion: Oxalate occurs as end product of metabolism and is easily Results: Both cases had a few glomeruli with global sclerosis, while the
eliminated in the stool or urine. However, under specific circumstances, majority were lobulated with diffuse thickening of the GBM, and some
excessive buildup of crystal deposits in the kidneys causes loss of renal had cellular crescents. Mesangial proliferation was revealed by PAS stain-
function. It is important to consider hyperoxaluria in patient who presents ing, while GBM spike formation and double-countorned membrane were
with unexplained material deposition in the tubular lumens, because ox- recognized on silver staining. Immunofluorescence on case 1 revealed
alate crystals might be missed under light microscope. granular deposits of IgA (2+/3+), C3 (1+/2+), IgG (faint staining) and
IgM (faint staining) along the GBM; case 2 had deposits of IgA (2+), C3
(1+) and C1q (2+). Both cases showed mononuclear cell infiltration of the
E-PS-16-004 interstitium.
A case report of collagenofibrotic glomerulopathy with a "full house" Conclusion: These two cases with simultaneous tubulo-interstitial and
pattern of immunohistochemistry staining. membranoproliferative glomerulonephritis, the latter not associated with
Z. Abdawn1, O. Cain2, E. Curtis1 cryoglobulinemia, expose the broad spectrum of renal involvement in
1
University Hospitals Birmingham NHS Foundation Trust, United Sjögren syndrome. Renal biopsy is essential to obtain an accurate diag-
Kingdom, 2 University Hospitals of Birmingham NHS Foundation nosis because glomerular commitment may affect the clinical manage-
Trust, Cellular Pathology, Queen Elizabeth Hospital, United Kingdom ment. Both patients are currently receiving prednisolone and mycophe-
nolate mofetyl, which is being well-tolerated and has resulted in renal
Background & Objectives: Collagenofibrotic glomerulopathy is a rare function stabilization.
renal disease which is characterised by accumulation of type III collagen
in the glomerular mesangial and subendothelial areas. Stains for immu-
noglobulins and compliments are usually negative. Here, we report a case E-PS-16-006
of collagenofibrotic glomerulopathy with a "full-house" pattern of Lupus-like membranous glomerulopathy in a patient under
immunohistochemistry. pembrolizumab: report of a rare case
Methods: Clinical case review and review of the topic in published clin- H. Gakiopoulou 1 , P. Korkolopoulou 1 , S. Havaki 2 , A. Stofas 1 ,
ical literature. A. Gkivalou3, E. Athanasiadis4, I. Giatras5, A. Gerakis5
Virchows Arch

1
1st Department of Pathology, School of Medicine, The National and Immunoperoxidase staining for Amyloid A was negative and DNAJB9
Kapodistrian University of Athens, Greece, 2 Department of Histology was positive. Mass spectrometry confirmed DNAJB9 without any amy-
and Embryology, School of Medicine, National and Kapodistrian loid signature. The findings were interpreted as CFGN.
University of Athens, Greece, 3 Department of Biology, The National & Conclusion: Congo red positivity in CFGN makes distinction from
Kapodistrian University of Athens Greece, 4 Department of Medical amyloidosis challenging. The underlying cause, treatment and the
Oncology, Mitera Hospital, Athens, Greece, 5 Department of prognosis for these entities are different. Amyloidosis generally
Nephrology, Hygeia Hospital, Athens, Greece warrants aggressive treatment and has poorer overall prognosis.
Mass spectrometry and immunostaining for DNAJB9 can make
Background & Objectives: Immune checkpoint inhibitors (ICPIs) have this distinction; with the latter being applicable in the routine di-
revolutionized the treatment of malignancies. Among them, monoclonal agnostic pathology lab. Pathologists and clinicians need to be
antibodies directed against programmed death 1 (PD-1), like aware of this entity and the pitfalls it presents to ensure accurate
pembrolizumab, prevent the engagement of PD-1 with its ligands, leading diagnosis.
to T-cell stimulation. The potent activity of ICPIs results in inflammatory
manifestations characterised as immune-related adverse events (irAEs).
Two different forms of ICPI-induced renal damage have been identified: E-PS-16-010
acute tubulointerstitial nephritis (TIN) and immune complex glomerulo- Anticoagulation related nephropathy in a post renal transplant
nephritis (ICG). To the best of our knowledge, until now, pembrolizumab patient
has been associated with TIN but not with ICG. We present a rare case of H. Tennekoon1, A. Kousios1, R. Gardiner1, L. Moran1, D. Goodall1, D.
a patient under pembrolizumab developing nephrotic syndrome due to a Taube2,1, J. Galliford1, C. Roufosse2,1
1
lupus-like membranous glomerulopathy. Imperial College Healthcare NHS Trust, United Kingdom, 2 Imperial
Methods: A 69- year-old woman with lung cancer metastatic to brain College London, United Kingdom
underwent immunotherapy with pembrolizumab. Eight months later, she
developed heavy nephrotic syndrome. Pembrolizumab therapy was Background & Objectives: Anticoagulation-related nephropathy
stopped and a renal biopsy was performed. (ARN) presents as acute kidney injury (ATI) during periods of over-
Results: Renal biopsy demonstrated a podocytopathy with a membra- anticoagulation. ARN has only been described once in a transplant.
nous pattern and a tubulointerstial nephritis. Immunohistochemistry Methods: N/A
[IgG4(-), PLA2R(-)] and immunofluorescence (full-house pattern) sug- Results: A 61-year-old-man 8-years post-transplant, on long term
gested a secondary, lupus like membranous glomerulopathy. anticoagulation with warfarin following mitral valve replacement
Immunihistochemistry for PD-L1 revealed staining in the glomerular presented to hospital with urosepsis. Serum creatinine was
capillary walls, some peritubular capillaries and rare epithelial tubular 224umol/L and INR 2.5. During treatment with antibiotics, serum
cells. creatinine and INR rose to 570umol/l and 3.5 respectively.
Conclusion: Although cases with TIN secondary to pembrolizumab ther- Anticoagulation was bridged from warfarin to heparin and a renal
apy have been reported, this is the first case of an immune complex lupus- biopsy was performed.
like membranous glomerulopathy related to pembrolizumab therapy. This The biopsy contained eight glomeruli. There was severe ATI with wide-
is also the first time that PD-L1 expression is demonstrated in the glomeruli spread red blood cell casts occluding the tubules. Moderate interstitial
of a patient under pembrolizumab suggesting a possible association be- oedema and inflammation with foci of severe lymphocytic tubulitis was
tween the glomerular damage and the irAEs of the check point inhibitors, seen. Occasional tubules contained neutrophil casts. There was no micro-
probably through disturbance of the tolerance against self-antigens. vascular inflammation. Moderate tubulointerstitial scarring was present.
C4d and SV40 immunostains were negative. Immunofluorescence was
negative for IgG, IgA, IgM, C3, C1q or kappa and lambda light chains.
E-PS-16-007 Electron microscopy showed dysmorphic RBC within tubules.
Congophilic fibrillary glomerulonephritis The biopsy was concluded as ARN with evidence of resolving urinary tract
H. Tennekoon1, T. Cook2,1, A. Palmer1, C. Roufosse2,1 infection and features of concomitant T-cell mediated rejection (Banff 1b).
1 2
Imperial College Healthcare NHS Trust, United Kingdom, Imperial Antibiotics were continued; however immunosuppression was not aug-
College London, United Kingdom mented in view of concomitant infection and frailty. He was started on
acenocoumarol aiming for INR 2-3. His renal function and inflammatory
Background & Objectives: Fibrillary glomerulonephritis is markers were back to baseline at discharge and at four month follow-up.
charactorised by IgG-positive, amyloid-like fibrils which are Congo red Conclusion: Given the limited management options, poor renal and
negative. The recent description of Congophilic fibrillary glomerulone- overall prognosis of ARN, transplant patients on anticoagulation
phritis (CFGN) changes this paradigm. should be monitored with the aim of early detection and prevention
Methods: N/A of ARN.
Results: A 65-year-old female with hypertension, hypercholesterol-
aemia and fatty liver disease was referred to nephrology for investi-
gation of haemoproteinuria. Her urine protein to creatinine ratio was E-PS-16-012
398mg/mmol, serum albumin 37g/L and serum creatinine Secondary paraneoplastic membranous glomerulopathy (MG) mim-
104Umol/L. A renal biopsy showed 20 glomeruli with increased icking serologically and histologically autoimmune lupus like MG
mesangium and segmental capillary wall thickening. These areas H. Gakiopoulou1, H. Theodoropoulou2, S. Havaki3, A.C. Lazaris1
1
were weakly PAS-positive and silver-negative. Congo red showed 1st Department of Pathology, School of Medicine, The National and
green-birefringence under polarized light in glomeruli with no stain- Kapodistrian University of Athens, Greece, 2 Renal Unit, General
ing in the vessels or interstitium. Four glomeruli were obsolete and 3 Hospital "Alexandra", Athens, Greece, 3 Department of Histology and
had segmental sclerosis, with moderate tubulointerstitial scarring. Embryology, School of Medicine, National and Kapodistrian University
Immunofluorescence staining showed mesangial and capillary wall of Athens, Greece
IgG and C3. IgA, C1q and IgM were negative. There was equal
intensity staining for kappa and lambda light chains. Electron mi- Background & Objectives: Paraneoplastic glomerulopathies are well docu-
croscopy showed non-branching fibrils (9.6 - 13.8 nm) in the mented and are related to altered immune responses in the presence of
mesangium and within glomerular basement membranes. malignancy.
 Virchows Arch

Methods: A 70-year-old male underwent a right radical nephrectomy in supported by the positive BRAF V600E mutation. In both adult and
2017, for a long standing renal mass thought to be an angiomyolipoma. paediatric patients, epithelioid glioblastoma has a particularly poor prog-
Pathologic diagnosis reported a clear-cell renal cell carcinoma with nosis compared to the run-of-the-mill glioblastomas, with a median sur-
perinephric fat invasion, without renal sinus invasion, with clear surgical vival of 6.3 months in adults and 5.6 months in children despite various
margins (pT3aN0). One year post-nephrectomy the patient presented with therapies.
proteinuria (3 g/day), mild decline of his renal function, ANA (+), anti-
Ro(+) and anti-ds-DNA(+), albeit asymptomatic for lupus. The patient
underwent a percutaneous biopsy to its sole left kidney. E-PS-17-002
Results: Light microscopy showed a glomerulopathy with a membra- Epithelioid glioblastoma: a report of 2 cases, including an extra-axial
nous morphologic pattern without morphological signs of secondary epithelioid glioblastoma initially misdiagnosed as rhabdoid
membranous glomerulopathy (MG). However, immunohistochemis- meningioma
try suggested a secondary MG (IgG4-, PLA2R-, TSH7DA -) and H.Y. Lee1, C.S.L. Ding1, M.M. Bundele1, K.L. Chuah1
1
immunofluorescence showed a full-house pattern with IgG+IgA+ Tan Tock Seng Hospital, Singapore
IgM+C3+C1q strong positivity, reminiscent of lupus MG. Electron
microscopy showed subepithelial and some mesangial electron dense Background & Objectives: Epithelioid glioblastoma, which was re-
deposits. The histological diagnosis was that of a secondary lupus- cently codified in the 2016 World Health Organisation classification
like MG. To determine the starting point of the MG, immunohisto- of central nervous system tumours, is rare. We describe 2 cases and
chemistry (C4d, IgG) was performed in the renal tissue adjacent to discuss the diagnostic challenges. Case 1: An 18-year-old male pre-
t h e c l e a r- c e l l c a r c i n o m a o f t h e n e p h r e c t o m y s p e c i m e n . sented with a left frontal lobe brain tumour. Case 2: An 18-year-old
Immunohistochemical markers of MG were negative suggesting that female presented with a left fronto-temporal intracranial extra-axial
the MG started after tumour resection. The clinical dilemma was if tumour.
we had to deal with a paraneoplastic secondary MG due to possible Methods: Case 1: The tumour showed epithelioid and rhabdoid cells.
tumour recurrence or with an additional autoimmune disease, like There was mitotic activity and abundant necrosis, but no microvas-
lupus. Patient’s investigation revealed metastatic thoracic lymph cular proliferation. Glial fibrillary acid protein (GFAP) and OLIG2
nodes rendering more possible the scenario of altered immunity trig- stained rare cells, and INI1 was intact. Positive immunohistochemi-
gered by the release of tumour antigens. cal staining for BRAF V600E supported the diagnosis of epithelioid
Conclusion: MG may precede not only the diagnosis of a primary glioblastoma. Case 2: The tumour showed rhabdoid cells. There was
neoplasm but also the discovery of its relapse. In this context, mitotic activity and necrosis, but no microvascular proliferation.
paraneoplastic MG may rarely mimic, serologically and histolog- Epithelial membrane antigen was positive, while GFAP was sparse.
ically, an autoimmune lupus-like disease. The tumour was diagnosed as a rhabdoid meningioma.
Results: The first patient died of disease 4 months post-surgery. In Case
2, following a multidisciplinary discussion where there was controversy
Sunday, 8 September 2019 – Wednesday, 11 September 2019 about whether the tumour could have an intra-axial component, the case
E-PS-17 | Neuropathology was reviewed at an external institution. There a diagnosis of epithelioid
glioblastoma was rendered based on focal staining for GFAP and OLIG2,
and no staining for somatostatin receptor 2. BRAF V600E mutation was
E-PS-17-001 negative. This patient showed no disease recurrence 24 months post-
Epithelioid glioblastoma: case report of a rare histological variant of surgery.
glioblastoma in a 17 year-old boy Conclusion: Epithelioid glioblastoma is rare, and the differential
F.F. Cheo1, K. Merchant2, J.G.C. Teo2, K.T.E. Chang2 diagnoses include metastases, atypical teratoid/rhabdoid tumour
1
Department of Anatomical Pathology, Singapore General Hospital, and rhabdoid meningioma. Possible sparse staining for GFAP, ab-
Singapore, 2 Department of Pathology and Laboratory Medicine, KK sence of microvascular proliferation, an often compact pattern of
Women's and Children's Hospital, Singapore growth, and a superficial or extra-axial location add to the diagnostic
challenges. OLIG2 staining and BRAF V600E mutation, if present,
Background & Objectives: Epithelioid glioblastoma is a rare variant may be helpful.
of IDH-wild type glioblastoma (WHO IV) which occurs predomi-
nantly in young adults and children. We report a case of epithelioid
glioblastoma diagnosed locally in KK Women’s and Children’s E-PS-17-003
Hospital, Singapore. Tumour-to-tumour metastasis: breast carcinoma metastasis to
Methods: The patient presents with worsening headache and vomiting meningioma
for a week. Magnetic Resonance Imaging (MRI) shows a 3.5 cm right S. Mata1, M. Mafra2
temporal solid mass with perilesional oedema and midline shift. 1
Patholology Department, Instituto Português de Oncologia de Lisboa,
Microscopically, the tumour demonstrates sheets of tightly packed pleo- Francisco Gentil, EPE, Portugal, 2 Serviço de Anatomia Patológica,
morphic epithelioid and rhabdoid cells, with abundant multinucleated Centro Hospitalar Universitário de Lisboa Central, EPE, Lisboa, Portugal
giant cells seen. Numerous mitoses with atypical mitotic figures are iden-
tified. Necrosis is present. Background & Objectives: The diagnosis of a dural based nodule in
Results: On immunohistochemistry (IHC), the tumour is positive for patients with history of malignancy is challenging and includes me-
GFAP, S100, vimentin and patchily positive for neurofilament and ningioma, dural metastasis, and much less likely tumour-to-tumour
EMA. Few tumour cells are highlighted by synaptophysin. The tumour metastasis. In a breast cancer patient, discernment of meningioma
is negative for pancytokeratin AE1/3. Wild type staining pattern is noted from metastasis is important because complete surgical resection
on P53. Cell proliferation index Ki67 (MIB-1) is approximately 30 to may be curative for the former, while radiotherapy would be typically
40% in the tumour. INI-1 (SMARCB1) and SMARCA4 are both retained employed for the latter. Imaging alone is often unspecific and histo-
in the tumour cells. In addition, BRAF V600E mutation is detected in this logical examination remains the only reliable diagnostic method
case using IHC method. IDH-1 mutation is negative(wild-type). whenever an accurate diagnosis is critical for clinical management.
Conclusion: The overall immunomorphological features are in keeping Methods: We describe an unusual case of a dural based nodule in a breast
with an epithelioid glioblastoma, WHO grade IV. This is further cancer patient proved to be a metastasis within an intracranial meningioma.
Virchows Arch

Results: A 51-year-old woman with breast cancer metastatic to lymph Background & Objectives: Malignant gliomas with heavily lipidized
nodes and bone, presented with a dural based nodule measuring tumour cells are extremely rare, with only limited case reports in the
18x19x19mm, suspicious for meningioma or dural metastasis on literature that were mostly published in the “pre-molecular” era.
MRI. Pathologic assessment of the surgical specimen revealed 2 dif- Recognition of this variant is important as it can masquerade as a
ferent morphologies: a meningothelial proliferation with syncytial lower grade localized glioma, such as a pleomorphic
and whorling patterns (EMA+) without mitosis or anaplasia; and an xanthoastrocytoma.
epithelial glandular component (mammaglobin+). The diagnosis was Methods: We report a case of a heavily lipidized variant of glioblas-
transitional meningioma (Grade I, WHO) infiltrated by an adenocar- toma with gliomatosis cerebri growth pattern in a 50-year-old man,
cinoma compatible with breast origin. Months later, parenchymal describe its clinicopathologic features and perform a literature review
brain lesions were identified. on this entity.
Conclusion: Clinicians and pathologists should be familiar with the Results: The tumour was composed of pleomorphic lipidized cells
possibility of intrameningioma metastases of carcinomas, a well- with abundant vacuolated cytoplasm. Focally, there were spindled
recognized although rare phenomenon with 34 recorded cases in cells with fibrillary cytoplasm reminiscent of a conventional
the literature. Given the challenges in differentiating a meningioma gliomatous component. Microvascular proliferation and necrosis
from breast cancer metastasis in imaging alone, surgical resection were noted. Both lipidized and spindled cells were positive for
should be considered in patients with history of breast cancer pre- GFAP and ATRX. Olig2 was positive only in the spindled cells.
senting with a dural based nodule. IDH1R132H was negative. Most patients documented in the litera-
ture were first diagnosed at an average age of 50 and their median
survival was a year or less.
E-PS-17-004 Conclusion: Distinguishing the heavily lipidized variant of glioblas-
Dysplastic cerebellar gangliocytoma (Lhermitee-Duclos disease) with toma from other tumours with abundant clear/vacuolated cytoplasm
frequent recurrences is critical as it confers serious prognostic and treatment implica-
C. Yoo1 tions. The rapidly fatal course of this tumour in most patients, an
1
St Vincent Hospital, The Catholic University of Korea, Republic of average presenting age of 50, negative IDH1R132H and retained
Korea ATRX suggest an IDH wild-type glioblastoma with no lower grade
precursor.
Background & Objectives: Dysplastic cerebellar gangliocytoma
(DCG, Lhermitte-Duclos disease) is a rare benign cerebellar tumour.
DCG forms an important part of multiple hamartoma-neoplasia com- E-PS-17-006
plexes (Cowden’s syndrome). Because of the possibilities of a con- Gliomas with abscesses: a report of two cases of astrocytic tumours
currence of other organ diseases, continuous follow-up is recom- with intra-tumoral neutrophilic abscess and literature review
mended for DCG. Clinically, DCG is known to show benign behavior K.A. Yeo1,2, M. Lee2
1
and recurrence is rare, but no extensive prognostic studies have been Division of Forensic Medicine, Health Sciences Authority, Singapore,
2
done. The aim of this case report is to present a DCG case which Department of Anatomical Pathology, Singapore General Hospital,
showed an unusual clinical course. Singapore
Methods: 70-year male visited St Vincent Hospital because of severe
dizziness. 18 years ago, he had undergone subtotal tumour removal for Background & Objectives: Abscesses within brain tumours are un-
the mass lesion in the left cerebellum. Two years later, he felt severe common; most are reported in sellar and parasellar tumours after
dizziness and MRI showed slightly increased mass size. Partial tumour direct extension from infected paranasal sinuses or from the ana-
removal was done. He hasn’t had any special symptoms since then. tomical “danger area” of the face. Cerebral gliomas with neutro-
Recently, he felt severe dizziness again, and MRI showed an ill-defined philic abscess formation are extremely rare, with few cases being
mass in the same place. tumour was removed and the patient is now under reported.
observation. Methods: We report two cases of astrocytic tumours with neutro-
Results: Pathologically, the cortical layer of the cerebellum was thick- philic abscesses found on histological evaluation, and review the
ened and normal cortical layers were effaced duo to the proliferation of literature of gliomas associated with abscesses reported from 1986
dysplastic ganglion cells. But the cerebellar gyrate architecture was pre- to 2018.
served. Purkinje cells were hardly observed and a few granule neurons Results: Two cases presenting with similar symptoms of headaches
were scattered between ganglion cells. Calcifications were found in the and altered mental status are reported. Neuroimaging identified a left
white matter. Pathologic findings were consistent with dysplastic cerebel- thalamic intraparenchymal mass in the first case, and a cystic lesion
lar gangliocytoma. in the right frontal lobe in the second case. The lesions were biopsied
Conclusion: Patient had experienced two relapses, first two years and showed malignant-appearing glial cells with intra-tumoral ne-
after surgery and second after a long period of disease-free interval. crotic material and neutrophils. Our literature review showed 18 re-
It is uncertain whether subtotal tumour removal was associated with ported cases of gliomas with abscess formation. Challenges to diag-
recurrence. Until today, evidence of concurrence of Cowden nosing gliomas with abscesses clinically, radiologically and histo-
syndrome-associated other organ diseases was not found. We report pathologically are also discussed.
this case to promote the understanding of the clinical course of this Conclusion: While gliomas with abscesses are rare, they are an
rare disease. important differential for intra-cranial space-occupying lesions.
Both the neoplastic and infectious components of the lesion are
important to recognize and diagnosis should be made in correlation
E-PS-17-005 with clinical, intraoperative, radiological and histopathological find-
Heavily lipidised variant of glioblastoma with gliomatosis cerebri ings.
growth pattern
N.J.H. Tan1, Y.L.J. Wong2, M.E. Nga1, C.L. Tan1
1
Department of Pathology, National University Health System, E-PS-17-007
Singapore, 2 Department of Diagnostic Imaging, National University Rare observation of recurrent papillary pineal tumour
Health System, Singapore S. Petrov1, T. Akhmetov1,2, N. Gizatullina1,3
 Virchows Arch

1
Kazan State Medical University, Russia, 2 Kazan Cancer Centre, Russia, glioma. In the second case by NGS mutations in FLT3 and p53
3
Interregional Clinical and Diagnostic Center, Kazan, Russia were found. Cytogenetic study detected deletion of CDKN2a.
Diagnose of anaplastic astrocytoma with neural differentiation
Background & Objectives: Papillary tumour of pineal region is a new was made.
entity in neurooncology added to WHO classification in 2003 (ICD-0 Conclusion: Some morphological features of low-grade neoplasms, seen
Code 9395/3). By 2016 only 182 cases were reported. in high-grade astrocytomas, could provide a hint towards mechanism of
A 33-year-old female was admitted with headaches, right sided pathogenesis of paediatric brain tumours.
hypesthesia, diplopia, left sided hearing loss, nausea and vomiting in
January 2019. Enhanced MRI revealed a 36*32*31 mm mass in the free
edge of cerebellar tentorium (suspected meningioma or recurrent pineal E-PS-17-009
tumour). Huntington disease in a female with 28-repeat CAG allele
Methods: First symptoms noticed in 2013, same year patient S. Jevtic1, J. Provias2
1
underwent resection of pineal neoplasm with ventriculoperitoneal McMaster University, Michael G. DeGroote School of Medicine,
shunting (diagnosis papillary tumour of pineal region). Symptoms Canada, 2 Department of Pathology and Molecular Medicine, Hamilton
appeared again in 2018, second operation (resection of tentorial Health Sciences, Canada
lesion) performed in February 2019. On operation soft friable lesion
extended to the right side from tentorial incisure, measured Background & Objectives: Huntington Disease (HD) is an
34*32*30 mm. autosomal-dominant inherited disorder that presents with chorea,
Results: Tumour histologically was represented by small eosinophil- psychiatric involvement, and dementia. The causative mutation is
ic cells with hyperchromic polygonal nuclei and detectable nucleoli, a CAG trinucleotide expansion in the huntingtin gene located on
arranged in solid and macropappilary structures. Fibrovascular stro- chromosome 4, where >36 repeats is disease-confirmatory.
ma contained areas of hyalinization, pseudoangiomatosis and However, an intermediate range from 27-35 repeats has been re-
perivascular pseudorosettes. Necrotic areas were absent, only scarce ported to lead to disease in rare cases. We report here an 81-year-
mitotic figures recognized. Immunohistochemistry: positivity for old female with clinical and autopsy-confirmed diagnosis of HD
GFAP, S100, vimentin, neuron-specific enolase, EMA, cytokeratins (CAG repeat = 28), which represents the lowest confirmed CAG
AE1/3, nuclear staining for p53, Ki67 4-5%, negative reaction for repeat to date.
synaptophysin. Methods: Gross examination of the brain was completed after which
Diagnosis: Relapse of papillary pineal tumour (WHO grade II). sections were formalin fixed and paraffin embedded for microscopic
Postoperative period with improvement of neurological state. examination. Immunohistochemical staining was done for: glial fi-
Conclusion: Due to papillary histological pattern, proximity to the brillary acidic protein, amyloid-beta, and tau. Immunofluorescence
cerebral aqueduct and symptoms related to hydrocephaly the newly staining involved p62 primary antibody with AlexaFluor 488 second-
added entity of Papillary tumour of pineal region should be consid- ary antibody.
ered in differential diagnosis with papillary ependimoma. Results: Brain autopsy revealed classic pathologic findings including
severe neuronal loss in the caudate and putamen, with accompanying
gliosis. p62 immunofluorescence showed rare intraneuronal inclu-
E-PS-17-008 sions suggesting minimal presence of huntingtin aggregates.
Congenital high-grade gliomas with features of maldevelopment of Interestingly, there was significant and diffuse concomitant
brain: review of 2 cases with molecular studies amyloid-beta plaque deposition with focal tau pathology, despite no
T. Mikhaleuskaya1, N. Konoplya1, A. Valochnik1, A. Punko1 signs of clinical dementia.
1
Belorussian Research Center for Paediatric Oncology, Haematology and Conclusion: This case highlights several interesting points, includ-
Immunology, Belarus ing: (1) the role of genetic testing in predicting risk of HD and
family testing, (2) the role of protein aggregates in disease pathol-
Background & Objectives: We report two cases of congenital high- ogy, and (3) co-occurrence of neurodegenerative diseases with over-
grade brain tumours, in which areas of low-grade tumours of lapping symptoms.
dysmorphogenetic origin – gangliocytoma and angiocentric glioma
were identified. Usually these tumours do not undergo malignancy. This work was supported by MacRES Scholarship.
In both cases large tumours of the right hemisphere were diagnosed pre-
natally. After birth they were subtotally removed and both of them re-
lapsed a few month later. E-PS-17-010
Methods: In the first case, histologically, the diffuse growing tu- Cervical meningioma presented with Brown-Sequard syndrome: a
mour consisted of bundles of low-differentiated spindle cells with a case presentation
network of small branching vessels. Mitotic activity was high. At Z. Asan1, A. Kilitci2, A. Yüceer1, î Aykanat1, E. Tugcugil3, F. Durna1, Z.
the periphery of the tumour astrocytic differentiation could be men- Kaya2
1
tioned, cells formed perivascular rosettes resembling angiocentric Ahi Evran University Medical Faculty, Dept of Neurosurgery, Turkey,
2
glioma. Immunohistochemistry revealed positivity for GFAP, D2- Ahi Evran University Medical Faculty, Dept of Pathology, Turkey,
3
40, EMA. Karadeniz Tecnical University Medical Faculty, Dept of
In the second, the morphology of the primary biopsy corresponded to Anesthesiology, Turkey
the gangliocytoma. Histological examination of a recurrent tumour
showed areas of gangliocytoma and solid sheets of undifferentiated Background & Objectives: The clinical picture that emerges from a loss
cells with high mitotic activity, Homer-Wright rosettes formation and of function in one half of the medulla spinalis in the vertical plane is
focal ganglionic differentiation. IHC revealed positivity for neural named as Brown-Sequard syndrome(BSS). This clinical picture usually
markers, olig2, p53. appears after trauma and its appearance due to a spinal cord tumour is
Results: In the first case molecular study didn’t reveal mutations in quite rare. Spinal meningiomas are the most prevalent extra-axial spinal
p53, H3K27, H3G34,IDHR132H, BRAF V600E. The only cyto- cord tumours encountered after metastases. Clinical findings are concerned
logical finding was loss of chromosome 6. The tumour was con- with the tracts where the spinal cord is impacted and radicular findings are
sidered anaplastic astrocytoma with features of angiocentric rarely seen.
Virchows Arch

1
Methods: 57-year-old female patient was evaluated due to com- Tunis El Manar University, Medicine School of Tunis Military Hospital
plaints of right hemiparesis, left hemihypesthesia, and ataxic gait. of Tunis, Department of Pathology, Tunisia
The cervical MRI examination of the case revealed a mass lesion
with a lateral localization at levels C4-C5 that demonstrated homog- Background & Objectives: Meningioma is the most common intra-
enous contrast enhancement, caused spinal cord compression, and cranial extracerebral tumours. The 2016 World Health Organization
was consistent with meningioma. (WHO) classification recognises many subtypes of meningioma.
Results: Histopathological and immunohistochemical examination of Secretory meningioma is a rare meningioma variant which is a
the light-brown material with a volume of approximately 3cc and a low grade tumour (Grade I). It accounts for 1% to 3% of all menin-
soft-consistency was consistent with grade 1 meningioma giomas with a predominance in female patients in the fifth decade. It
(meningothelial type). After the operation, improvement was ob- is different from other subtypes, not only because of its pathological
served in motor strength, ataxia, and sensory deficits in the presented features but also because of its clinical features as well. Our aim is
order. No additional neurological deficits were encountered during to discuss clinical and pathological features of this rare variant of
the 4-year long-term follow-up period and tumour recurrence was not meningiomas.
determined in radiological follow-up. Methods: We report a case of a 57-year-old woman who presented with
Conclusion: In the BSS, all tracts in one half of the spinal cord are seizures. MRI showed an extracerebral temporal process that was en-
expected to experience a loss of function. However, clinical findings are hanced after gadolinium injection. Total exision of the lesion was per-
associated with the dominant corticospinal tract, spinothalamic tract, and formed. We recieved a firm, white and lobulated nodule that measured
dorsal column tracts. In this picture, which typically follows cord 25 mm in diameter.
hemisection, partial/total recovery of neuronal function can be observed Results: Microscopic examination revealed a diffuse, lobulated
if there had not been a total loss of function due to compression. proliferation composed of menigothelial cells with "whorls" for-
Treatment is total resection. mation. Tumour cells were medium-sized, with abundant eosino-
philic cytoplasm and monomorphic nuclei arranged in a syncitial
pattern. Intracellular lumina containing periodic-acid-Schiff (PAS)
E-PS-17-011 - positive eosinophilic secretions called pseudopsammoma bodies
Next generation sequencing-identified IDH-1, ATRX, TP53 mutation were observed. Mitoses were not seen. The tumour has infiltrated
and MYCN amplification in glioblastoma with primitive the dura. The edge between the tumour and the cerebral paren-
neuroectodermal tumour-like feature and extensive subarachnoid chyma could'nt be evaluated. Pseudopsammoma bodies showed
spread: a case report immunoreactivity for carcinoembryonicantigen (ACE) and the sur-
H. Hwang1, K.S. Lee1, H.S. Lee1, G. Choe1,2 rounding tumour cells were positive for both ACE and
1
Department of Pathology, Seoul National University Bundang Hospital, Cytokeratin AE1/AE3. We concluded a seretory meningioma
Republic of Korea, 2 Department of Pathology, Seoul National University grade I (WHO 2016).
College of Medicine, Republic of Korea
Conclusion: The diagnosis of secretory meningioma may be chal-
lenging in some cases. Clinical and imaging features are similar to
Background & Objectives: In recent years, there have been numerous
other meningioma subtypes. However, pathological features may
molecular studies of glioblastoma. With regard to glioblastoma
lead to differential diagnosis as psammomatous, chordoid,
showing extensive subarachnoid spreading, however, the pathogene-
microcystic subtypes of meningioma or metastatic carcinoma.
sis remains to be determined due to its low incidence. Present report
Immunohistochemistry is an essential tool to make the diagnosis
describes a rare case of glioblastoma with primitive neuroectodermal
and to rule out other diagnosis.
tumour (PNET)-like feature, which spread extensively in subarach-
noid space, as well as the result of its molecular analysis using next
generation sequencing (NGS).
Methods: A 37-year-old male presented with a new onset, severe headache. E-PS-17-013
Magnetic resonance imaging revealed a diffuse infiltrative mass in the right A case of central neurocytoma: an uncommon neoplasm, examined
in frozen and FFPE sections
frontal lobe, spreading broadly in subarachnoid space. The patient
A. Baliaka1, M. Kilmpasani1, N. Pastelli1, S. Kottas2, I. Karafoulidou1, I.
underwent craniotomy and tumorectomy. Microscopically, glioblastoma
showed PNET-like feature. On immunohistochemical analysis, tumour cells Matzarakis1, S. Papaemmanouil1
1
focally expressed GFAP and synaptophysin. IDH-1 (p.Arg132His) mutation Department of Pathology, General Hospital of Thessaloniki "G.
was found in the subsequent NGS test. Additionally, two frame shift genetic Papanikolaou", Greece, 2 Department of Neurosurgery, General
alterations were found: ATRX (p.Tyr2208fs) and TP53 (p.Pro301fs). Hospital of Thessaloniki "G. Papanikolaou", Greece
Results: Interestingly, MYCN amplification was also present, identified
by both NGS and fluorescence in situ hybridization (FISH) test. Despite Background & Objectives: Central neurocytomas account for 0.1-0.5%
post-operative therapies including temozolomide and radiotherapy, the of all brain tumours. According to WHO classification, it is a neoplasm
tumour progressed aggressively and the patient expired nine months after with uncertain biological behaviour. We present the case of a 21-year-old
the first symptom onset. man, suffering from headaches, with an enhancing intraventricular tu-
Conclusion: Although there have been previous reports of MYCN ampli- mour on imaging.
fication in glioblastoma with PNET-like feature, this is the first case report Methods: The tumour protruded into the right lateral ventricle and was
of IDH-mutant type glioblastoma with such features. IDH-1 mutation and accessed via minimally invasive approach. Intraoperatively, tissue mate-
younger age are usually associated with a better prognosis in glioblasto- rial was sent for frozen sections. Subsequently, a gross total resection was
ma. However, this case suggests that when MYCN amplification coexists undertaken. The obtained material was examined with hematoxylin-eosin
in IDH-mutant type, the tumour behavior could be contrarily aggressive. and immunohistochemical stains.
Results: The frozen sections, as well as the formalin-fixed paraffin-em-
bedded tissue sections, demonstrated a neoplasm, consisting of mono-
E-PS-17-012 morphic, round cells, carrying uniform, round-to-oval nuclei, with finely
A case report of a rare variant of meningioma dispersed chromatin. Mitoses were rare. Numerous, thin-walled, capillary
I. Msakni1, N. Mansouri1, R. Hedhli1, F. Gargouri1, A. Saidi1, A. vessels were evident between the cells. Necrosis or calcifications were
Bouzaini1, B. Laabidi1 absent.
 Virchows Arch

The neoplastic cells were positive for CD56, synaptophysin, NSE, Background & Objectives: Gliosarcomas comprise 2% of all glioblas-
S-100, and negative for CAM5.2, chromogranin, and GFAP, tomas, with similar clinical manifestation and equally poor survival rate.
among others. The proliferation index Ki67 was expressed in 1- They affect middle-aged adults with a male predominance. We present
2% of the neoplastic cells. In correlation with the patient age and the case of a 50-year-old male, with a recurring tumour in the right
the location of the tumour, the diagnosis was central neurocytoma. temporal lobe. He had reportedly received surgical treatment for a glio-
Postoperatively and in the follow-up, the patient recovered very blastoma at the same site 3 months ago.
well with no neurological deficits. Methods: The patient underwent surgical excision for tumour-mass-
Conclusion: Central neurocytomas are rare neuroepithelial tumours, reduction therapy before radiotherapy. We received multiple, white-tan,
with neuronal immunophenotype and usually low proliferation in- tissue fragments, measuring 4x3.2x0.6 cm. Tissue sections were exam-
dex. They are predominantly found in young adults, attached to ined with hematoxylin-eosin and immunohistochemical stains. We ob-
septum pellucidum, causing symptoms of increased intracranial served a biphasic tumour with alternating areas, displaying glial and sar-
pressure. They are surgically well-manageable, with a 5-year sur- comatous differentiation. The gliomatous component consisted of pleo-
vival estimated at 90%, more favourable for intraverticular tu- morphic and anaplastic astrocytes, with the presence of necrotic areas and
mours and those who achieve complete resection. Patient age, prominent endothelial proliferation. The predominant sarcomatous com-
high Ki67 expression and comorbidity are considered adverse ponent consisted of spindle cells, arranged in anastomosing fascicles, and
prognostic factors. single, atypical giant-cells with pleomorphic, vesicular nuclei. Mitotic
activity was increased, with several atypical mitoses.
Results: The immunohistochemical expression of GFAP was evident in
E-PS-17-014 the gliomatous component and almost absent in the sarcomatous compo-
A case of intraparenchymal atypical meningioma in a 3-year old boy nent, with scattered positive atypical giant-cells. P53 was expressed in
S. Lypiridou1, N. Foroglou2, G. Karayannopoulou1, E. Antoniadis2, A. both components, while S100, IDH-1 and CK8/18 were completely neg-
Cheva1 ative. Ki-67 staining index was 20-40%.
1
Pathology Department, Faculty of Medicine, Aristotle University of The final diagnosis was secondary gliosarcoma.
Thessaloniki, Greece, 2 1st Department of Neurosurgery, AHEPA Conclusion: Gliosarcomas are a rare variant of glioblastoma, which cor-
Hospital, University of Thessaloniki, Greece respond histologically to WHO grade IV. They contain distinct
gliomatous and sarcomatous components, which seem to have a common
Background & Objectives: Meningiomas are the most common be- cytogenetic background, as indicated by molecular studies. Secondary
nign tumours of the central nervous system. The vast majority of gliosarcomas are exceedingly rare. The literature on secondary
them correspond histologically to WHO grade I. They rarely ap- gliosarcoma illustrates a more favorable survival than for primary
pear in childhood, representing only 2.8% of all paediatric primary gliosarcoma, although it still remains limited.
brain tumours. Intraparenchymal localization is even more uncom-
mon. We present the case of a 3-year-old boy with an emerging,
contrast-enchancing, highly vascularized parenchymal mass, locat- E-PS-17-016
ed in the frontal and temporal lobes. Impact of IDH1 mutation on long-term survival in patients with
Methods: We received multiple, white-tan, soft, tissue fragments, diffuse brain glioma
measuring 8x7.8x0.9 cm. Tissue sections were examined with E. Ochirjav1, G. Choe2, T. Baldandorj1, B. Enkhbat1
1
hematoxylin-eosin and immunohistochemical stains. Mongolian National University of Medical Sciences, Mongolia, 2 Seoul
Microscopically, the tumour mainly consisted of uniform, spindle National University Bundang Hospital, Republic of Korea
cells, arranged in whorls, fascicles and rare small groups.
Occasionally, cells with atypical features were encountered. Background & Objectives: Diffuse brain gliomas are common primary
Psammoma bodies were infrequent. The mitotic activity was low brain tumour associated with a poor prognosis. In this study, we aimed to
(1/ 10 HPF). Invasion of the brain parenchyma was evident, in the determine the impact of IDH1 mutation status on long-term survival.
form of irregular, tongue-like protrusions of tumour cells. Methods: Patients who underwent surgery for diffuse brain glioma were
Results: The neoplastic cells were immunoreactive for vimentin and selected. Based on IDH1 mutation status, patients were separated into
EMA and negative for GFAP, S100, CD56, NSE, CD99, MelanA, IDH1 mutant and IDH1 wildtype groups.
Desmin, SMA, h-caldesmon, CK8/18 and CD34. Ki-67 staining index Results: A total of 124 patients with diffuse brain tumour were included
was approximately 7-10%. The final diagnosis was atypical (mean age 39±17, 48.4% male). The frequency of IDH1 mutant and
intraparenchymal meningioma. The patient died a few months after the IDH1 wildtype were 56.5% (n=70) and 43.5% (n=54), respectively.
diagnosis. During follow-up, 76 patients (61.3%) died and the median follow-up
Conclusion: Intraparenchymal meningiomas should be considered was 8 months (IQR 4; 16). Patients with IDH1 mutant more likely youn-
when other common lesions are excluded. Atypical meningioma ger (36±16 vs. 43±17, p<.05) and had low grade (grade II) tumour (64.3%
is an intermediate grade tumour and corresponds histologically to vs. 20.4%, p<.001). After adjustment of possible predictors, such age,
WHO grade II. The case of an intraparenchymal atypical meningi- gender, tumour location and surgical type, IDH1 mutant was an indepen-
oma in childhood is rarely encountered. The presence of brain dent predictor of all-cause mortality (HR=0.43, 95% CI 0.26-0.71,
invasion is associated with higher mortality and recurrence rate. p<.001). Kaplan-Meier estimation showed IDH1 mutant is associated
A detailed histological approach is mandatory for therapy- with longer survival compared with IDH1 wildtype in low grade tumour
planning and prognosis assessment. (log rank p<.001).
Conclusion: Mutated IDH1 is an independent predictor of all-cause mor-
tality in patients with diffuse brain glioma and resulted in longer survival
E-PS-17-015 compared with IDH1 wildtype.
A secondary gliosarcoma in the setting of a previously diagnosed
primary glioblastoma
S. Lypiridou1, A. Spiliotopoulos2, K. Papadopoulou2, A. Cheva1 E-PS-17-017
1
Pathology Department, Faculty of Medicine, Aristotle University of Adult gliofibroma: report and discussion of a rare case
Thessaloniki, Greece, 2 Neurosurgical Department of Aristotle M.G. Lisievici1, D. Pasov1, L.C. Cocosila1, F. Pop2, A.C. Lisievici3, F.M.
University of Thessaloniki, AHEPA Hospital, Greece Brehar1, G. Petrescu1
Virchows Arch

1
Bagdasar-Arseni Clinical Emergency Hospital, Romania, 2 Dr. Carol E-PS-17-019
Davila Clinical Hospital, Romania, 3 Carol Davila University of A case series of diffuse midline gliomas harboring H3 K27M
Medicine and Pharmacy, Bucharest, Romania mutation
L. Barona García1, B. Ferri Ñíguez2, M.A. Torroba Carón1, D. López
Background & Objectives: The term of gliofibroma was first pro- Motos2, T. Ribalta Farres3, A. Salazar Nicolás1, M.I. Oviedo Ramírez1,
posed in 1978 describing a biphasic tumour of glial and M.I. Ortuño Moreno1, A. Caballero Illanes1, E. Martínez Barba1
1
mesenchimal morphology. While the glial component may be of Servicio de Anatomía Patológica, Hospital Clínico Universitario Virgen
varying grade, the mesenchimal one is always benign. Most of the de la Arrixaca, Spain, 2 Hospital Clínico Universitario Virgen de la
cases described to date seem to affect the younger population, Arrixaca, Spain, 3 Hospital Sant Joan de Dèu Barcelona, Spain
rarely exceeding the age of 20. Only a few adult patients have
been reported. Background & Objectives: Brainstem gliomas are very uncommon
Methods: Our patient, a 64 years old man, was referred to our hos- tumours. They mainly occur in children and sometimes in young
pital for headaches, nausea, dizziness and tinnitus. Initial neuroimag- adults. “Diffuse midline gliomas with histone H3-K27M mutation”
ing described a large, temporal, apparently extraneuraxial mass with is a newly recognized entity in the revised 2016 World Health
cystic/necrotic areas. Later examination also showed an infiltrating Organization classification. Classied as grade IV, even when mitot-
nature of the tumour. ic figures, microvascular proliferation, and necrosis are not ob-
During surgery, the neurosurgen could not asess the exact origin served, these tumours are aggressive and predict a poor prognosis
and described the mass as very adhesive to both meninges and for the patient.
brain tissue. Methods: Retrospective review to determine the prevalence, morpholog-
A small fragment was sent for intraoperative examination. Frozen ic features and outcome of “Diffuse midline gliomas with histone H3-
sections as well as the squash technique revealed a mesenchimal, K27M mutation” diagnosis in our center since 2016.
apparently fibrous lesion which was interpreted as fibrous Results: 3 patients with brainstem gliomas were identified. 1 was
meningioma. female and 2 were male. Age at diagnoses was 1, 8 and 9 and
A subtotal resection was performed. magnetic resonance (MR) images showed that their tumours were
Results: Macroscopically, the tumour fragments, totalizing 8/7,5/3 cm, located in the third ventricle, cerebellopontine anlge and thalamus.
were grayish-white, firm and slightly rubbery. Light microscopy revealed Pathology demonstrated a primitive neuroectodermal tumour arising
a large fibrous, hypocellular, collagenized component embedding small within low grade astrocytoma in one case, diffuse astrocytoma in
areas of a high grade infiltrating glioma. the second and high grade astrocytoma in the third. All 3 samples
While not dominant, the glial component showed both mitotic activity as were negative for the IDH1 R132H mutation by immunohistochem-
well as necrosis and hints of vascular proliferation. istry and positive for the H3 K27M mutation. First patient died 4
Our final diagnosis was of anaplastic gliofibroma, which was later sup- years after diagnosis, the other two continue in treatment with 7 and
ported by immunohistochemestry. The patient was referred to an 16 months of survival.
oncologist. Conclusion: This newly defined entity represents a critical diagnostic
Conclusion: Tumours of a biphasic mesenchimal-glial nature are challenge for practicing surgical pathologists. These cases underline the
not extremely uncommon, usually consisting of gliosarcomas in importance of molecular evaluation to correctly subtype gliomas due to
adults and desmoplastic infantile astrocytoma/gangliogliomas in its prognostic and clinical significance.
children. Gliofibroma however, appears to be a distinct entity
which makes prognosis and treatment options difficult to assess.
Documenting the existing cases should help further understanding E-PS-17-020
of these tumours. Glioblastoma with carcinomatous differentiation or tumour-to-
tumour metastasis?
A. Fioravanzo1, M. Simbolo1, D. Giampiccolo2, R. Damante2, G. Pinna2,
E-PS-17-018 A. Scarpa3, V. Barresi1
1
A rare case of glial tumour with metastasis Department of Diagnostics and Public Health, Section of Anatomical
D. Lange1, A. Stanek-Widera1, M. Biskup-Fruzynska1, R. Lach1, B. Pathology, University and Hospital Trust of Verona, Italy, 2 Department
Nikiel1 of Neurosciences, Unit of Neurosurgery, Hospital Trust of Verona, Italy,
1 3
Tumour Pathology Department, Maria Sklodowska-Curie Memorial Department of Diagnostics and Public Health, Section of Anatomical
Cancer Center and Institute of Oncology, Gliwice Branch, Poland Pathology and ARC-Net Research Center, University and Hospital Trust
of Verona, Italy
Background & Objectives: Extraneural metastases of glial tumours
are rare, with approximately 2% incidence. The authors present a Background & Objectives: Glioblastomas can be heterogeneous neo-
case of a 68-year old woman who was diagnosed with a right tem- plasms with carcinomatous components of challenging interpretation.
poral lobe tumour measuring 2,5 cm in 2010. The patient did not Herein we describe a glioblastoma with carcinomatous features and clues
agree to the suggested treatment, but was operated on after 4 years for differential diagnosis between aberrant differentiation and tumour-to-
due to progression (the tumour increased in size to 5,5 cm). tumour metastasis.
Methods: The diagnosis of anaplastic oligodendroglioma G3 was Methods: A 70-year-old man presented with a month history of motor
established on the basis of histological images in H&E stain and and speech difficulties and mood deflection. Magnetic resonance imaging
immunohistochemical assays. 3 years later the patient presented with revealed an inhomogeneous frontal mass with ring enhancement. Total-
right cervical lymphadenopathy, which resulted in lymphadenecto- body computed tomography identified a solid lesion in the left lung with
my. After performing a wide panel of immunohistochemical stains mediastinal multi-nodal involvement. The patient underwent surgical re-
and confirming 1p19q loss of heterozygosity in both primary tumour moval of the brain mass and biopsy of the lung tumour.
and the nodal metastasis. Histopathological, immunohistochemical and molecular analyses were
Results: The patient was diagnosed with an extraneural (nodal) metasta- carried out on both tumours.
sis of oligodendroglioma. Results: The brain tumour showed two intermingled components: one
Conclusion: The patient survived six months after the confirmation of the with glioblastomatous morphology; one with carcinomatous morphology.
metastatic disease, with no signs of progression. The former was positive for GFAP and OLIG-2, while the latter was
 Virchows Arch

positive for cytokeratin AE1/AE3, CK7 and NapsinA and negative for Results: A 75-year-old man presented to the neurology department of
TTF-1. Molecular analysis revealed KRAS Gly12Asp and AKT1 mutation Samuel Libânio Hospital (Pouso Alegre, MG, Brazil) with a complaint of
in the carcinomatous, but not in the glioblastomatous component; none of paresthesia in the lower limbs. Magnetic nuclear resonance was per-
the components had IDH1/IDH2 or ATRX mutations. The pulmonary formed, demonstrating an intracanal, extradural, lobulated solid lesion
lesion was a primary adenocarcinoma (CK7, TTF-1 and NapsinA posi- located in the left posterolateral epidural region of L3-L4, compressing
tive) with KRAS Gly12Asp mutation. and deforming the dural sac and the cauda equina roots. In the histopath-
Conclusion: Molecular features indicated that the brain tumour was ological analysis, it showed fragments of fibroadiposal connective tissue
an IDH wild-type glioblastoma containing a metastasis from lung and hyaline cartilage, histologically benign, well differentiated, mature,
adenocarcinoma, with loss of TTF-1 expression and AKT1 mutation suggestive of a Chondroma without evidence of anaplasia. This diagnosis
acquisition during metastatization. Metastases to glioblastomas are was confirmed by immunohistochemical examination revealing that the
exceedingly rare and this is the first report supported by molecular chondroid nodulation observed corresponds to a small chondroma of soft
analysis. parts with positivity for S-100 protein.
Conclusion: Based on our experience, we propose that chondromas
should be considered as a differential diagnosis in the assessment of
E-PS-17-021 spinal tumours.
Intracranial hemangiopericytoma: a case presentation
A. Baliaka1, M. Kilmpasani1, N. Pastelli1, I. Dimitriadis1, I. Matzarakis1,
I. Karafoulidou1, S. Papaemmanouil1 E-PS-17-023
1
Department of Pathology, General Hospital of Thessaloniki "G. Papillary Glioneuronal Tumour (PGNT) in a 12 years old girl: a case
Papanikolaou", Greece report of a rare CNS neoplasm
L.L. Sousa Veras1, A. Costa Rendeiro1, N. Soares de Menezes2,1, R.
Background & Objectives: Central nervous system Manuel Reis1, M. de Medeiros Matsushita1
1
hemangiopericytoma (HPC) is a rare, dural-based neoplasm, accounting Barretos Cancer Hospital, Brazil, 2 European Society of Pathology,
for <1% of all intracranial tumours. It arises from the Zimmerman Brazil
pericytes and postcapillary venules and usually affects adults in the 4th-
6th decade of life. Background & Objectives: A 12 years old girl with generalized tonic-
Methods: A 70-year-old woman presented to our Hospital suffering from clonic seizure in the last 3 weeks, in use of anticonvulsant therapy and
tinnitus and headaches. Radiological evaluation revealed a hyperdense, normal neurological examination. MRI showed an expansile solid-cystic
highly vascular, dural-based lesion in the left temporal region. lesion in the left temporal lobe, with ill-defined limits, measuring 3.5 x
Intraoperatively, tissue material was sent for frozen sections. 2.6 x 3.1 cm. The imaging studies suggest a low-grade glial lesion or a
Subsequently, a gross total resection was undertaken. tumour of neuronal lineage and the lesion was totally resected. This case
Results: The histological examination revealed a neoplasm report intends to present an exceedingly rare CNS neoplasm.
characterised by high cellularity with closely apposed ovoid or Methods: Microscopically, it is a biphasic tumour, with cells arranged in a
spindle cells with mild to moderate atypia, arranged in a haphazard perivascular fashion forming pseudopapillary structures. A layer of cuboidal
pattern, surrounding numerous, thin-walled, branching vessels to fusiform glial cells is seen lining the hyalinized vessels which are strongly
(SMA+, CD31+, CD34+). A rich network of reticulin fibers positive for GFAP. A neuronal cell population is seen variably admixed with
(Gomori+) typically invested individual tumour cells. Focal necro- glial cells exhibiting immunoexpression for synaptophysin. Mitoses, micro-
sis and 4-5 mitoses per 10 HPF were also observed. vascular proliferation and necrosis are absent. Ki-67 is positive in less than
Immunohistochemically, the neoplastic cells were strongly positive 1% of tumour cells and EMA was negative.
for CD34 and focally for BCL-2 and SMA and negative for Results: The morphological findings and the immunohistochemical profile
CAM5.2, EMA, Vimentin, S-100, CD57, CD31 and desmin. The corroborate the diagnosis of PGNT, WHO grade I. PGNT is a rare, low-
proliferation index Ki67 was expressed in 5% of the neoplastic grade biphasic neoplasm (glioneuronal) with pseudopapillary architecture,
cells. The morphological and immunohistochemical features fa- representing less than 0.02% of intracranial tumours. It affects young adults
vored the diagnosis of a grade II HPC. (mean age 27 years). The most common location is supratentorial mainly in
Conclusion: Intracranial hemangiopericytoma (HPC) is a rare neoplasm the temporal lobe. The translocation t (9; 17) (q31; q24), resulting in a fusion
that remarkably mimics a meningioma clinically and radiologically; thus, oncogene SLC44A1-PRKCA, is present in a high proportion of cases.
the detailed histopathological review is the only means of its accurate Conclusion: Most PGNTs have an indolent behavior but a minority
diagnosis. Total surgical resection, when feasible, is the first choice of of the cases present atypical morphological features or late biolog-
treatment in all the cases of HPC. In case of malignant HPC, postopera- ical progression. There have been reports of extraneural metastases
tive radiotherapy is strongly recommended even after an apparently com- involving the pleura bilaterally and the left breast, 4.5 years after
plete tumour resection. the initial resection.

Program of Assistance and Incentive to the Researcher (PAIP) - Pio XII

E-PS-17-022 Foundation, Barretos, SP
Chondroma in the lumbar spine: case report
F. Mundim1, M. Engelman1, R. Grande1, S. Vasconcelos1, A. Fontes1, B.
Godoy1, G. Assis1, R. Gusmao1, T. Guimaraes1, P. Mundim2 E-PS-17-024
1
UNIVAS, Brazil, 2 UNIFENAS, Brazil Intratumoral heterogeneity in a paediatric posterior fossa group-A
ependymoma: a case report
Background & Objectives: Chondromas are benign tumours that rarely A. Araki1, M. Kool2,3, J. Gojo4, I. Slavc4, T. Czech5, C. Haberler1
1
present within the lumbar spine. Although chondromas are generally Institute of Neurology, Medical University of Vienna, Austria
2
asymptomatic, they can cause many neurological symptoms of slow de- Hopp Children's Cancer Center at the NCT Heidelberg, Heidelberg,
velopment. Careful preoperative diagnosis and complete removal of the Germany, 3 Division of Paediatric Neurooncology of the German
tumour are important due to transformation into malignant neoplasia. Cancer Research Center, Heidelberg, Germany, 4 Department of
Methods: Analyzing medical records with patient's permission and re- Paediatrics, Medical University of Vienna, Austria, 5 Department of
specting confidentiality. Neurosurgery, Medical University of Vienna, Austria
Virchows Arch

Background & Objectives: Ependymomas represent the third most are tumour size and mitotic rate. Treatment includes surgical resection or
common brain tumours in children. DNA methylation patterns unraveled targeted chemotherapy and EGFR tyrosine kinase inhibitors.
considerable heterogeneity classifying into nine molecular subgroups in-
cluding posterior fossa group-A (PFA) and B tumours. PFA-
ependymomas are most frequent in children and associated with a less E-PS-17-026
favorable prognosis than PFB ependymomas. Within PFA-ependymomas Intracerebral schwannoma in a 20-year-old girl: a case report
chromosome 1q gain proved as poor prognosis marker. PFA B. Laabidi1,2, R. Hedhli1,2, R. Yaich1,2, N. Mansouri2, F. Gargouri2, A.
ependymomas could be further classified into nine subtypes with PFA- Saidi1,2, A. Bouziani2, I. Msakni2
1
1c enriched for 1q gain. To date, intratumoral heterogeneity has not been Tunis El Manar University, Medicine School of Tunis, Tunisia,
2
described in ependymomas. We report a PFA-1c tumour showing two Military Hospital of Tunis, Department of Pathology, Tunisia
distinct tumour parts with different histopathological and genomic
alterations. Background & Objectives: Intracerebral schwannoma is an extremely
Methods: A 2.5-year-old female presented with a brain tumour in the rare brain tumour accounting for about 6 to 8% of all primary intracranial
fourth ventricle. Despite total resection, postoperative RTX and CTX she tumours. It is typically occurring at middle age.
died 4 years after diagnosis. Histopathological analysis, FISH, and DNA We report our experience with the diagnostic management of this entity
methylation profiling was performed using formalin-fixed paraffin-em- through a case report describing its clinical, radiological and pathological
bedded (FFPE) tumour tissue. features.
Results: Histological examination revealed two morphologically differ- Methods: The present report is of a 20-year-old female who presented a
ent parts: part-I had characteristic features of an anaplastic ependymoma cystic and solid parietal mass. The patient presented seizures and elevated
with chromosome 1q gain, part-II demonstrated an unusual morphology intracranial pressure. Neuroradiologic features showed a right parietal
with small gemistocytic astrocytes reminiscent of astrocytoma with bal- lesion with cystic and tissular components, intensely enhanced after
anced chromosome 1. DNA methylation profiling classified both tumours injecting intravenous gadolinium. The tumour was removed through a
as PFA-1c, yet copy umber profiles were different with 1q gain and 10q right parietal craniotomy.
loss in part-I, and a balanced chromosome 1 and chromosome 2, 9, 11 and Results: Histological and immunohistochemical findings confirmed the
17 gains in part-II. diagnosis of intracerebral schwannoma. The patient is alive without pro-
Conclusion: This case illustrates that different molecular subclones may gressive local disease or metastasis.
be present in EPN and emphasizes the importance to control the morphol- Conclusion: Intracerebral schwannoma is an extremely rare benign tu-
ogy of tumour tissue used for molecular analyses. mour. It is important to recognize it, particularly in younger patients,
given its benign nature, radiological resemblance to other tumours and
favorable response to surgical removal without toxic treatment.
E-PS-17-025
Multiple Sclerosis and bronchoalveolar carcinoma: a double case
study report E-PS-17-027
I. Dimitriadis1, N.D. Savvidou2, D. Kamplioni2, P. Konstantinidou2, F. Review of ependymal tumours in La Paz University Hospital
Louka2, D. Anestakis2 R.S. Melean Jauregui1, O. Cerezo Aranda1, N. Ibarra Soraluce1, A.
1
Department of Pathology, General Hospital of Thessaloniki "G. Pezzella Risueño1, R. Regojo1, I. Esteban-Rodriguez1
Papanikolaou", Greece, 2 Department of Autopsy Histopathology, 1
Hospital Universitario La Paz, Spain
Aristotle University of Thessaloniki, Greece
Background & Objectives: To review the clinical records of all
Background & Objectives: Multiple sclerosis (MS) is a chronic auto- ependymal tumours diagnosed in La Paz Hospital between 2000 and
immune disorder of the CNS that induces the formula of plaques-areas 2018.
characterised by demyelination, axon loss and oligodendrocyte death. MS Methods: We searched our database for all subependymomas,
is accompanied by disturbances of sensory-motor and autonomic myxopapillary ependymomas and ependymomas and collected clinical
functions.Bronchoalveolar carcinoma (BAC) is defined as a lung adeno- data about age, location, histomorphology, treatment and outcome. Grade
carcinoma which presents a non-invasive lepidic growth and is predom- was reviewed and given in accordance to WHO 2017 criteria.
inantly asymptomatic.Thefollowing case is of considerable interest due to Results: Among 45 ependymal tumours, the most common were
the rare combination of both diseases. ependymomas (36 cases) followed by myxopapillary ependymomas (7)
Methods: We received histological sections of brain, lung, kidney, liver and subependymomas (2). Ependymomas were frequently located in the
and heart tissue samples. The samples were studied posterior fossa whereas myxopapillary ependymomas and
immunohistochemically with appropriate antibodies. subependymomas were spinal. Of the 13 cases diagnosed in children
Results: Histological section of brain tissue presents edematous areas, (mean age 5) most of them were located in the posterior fossa (69%)
reactive astrocytes, as well as cell autolysis/degeneration, perivascular and half of them recurred even when complete resection was achieved.
lymphocyte accumulation, hemorrhagic infiltrations and capillary con- In adults (mean age 44): 2 subependymomas, 7 myxopapillary
gestion in several locations.Examination of lung tissue shows edema, ependymomas and 23 ependymomas were diagnosed. The most frequent
signs of pneumonia/ pulmonary fibrosis.Characteristics of neoplasia are location was the spine and the majority were grade II. Posterior fossa
also detected, including adenoid formations and disseminated squamous tumours recurred the most and were mainly partially resected.
cells with relatively abnormal nuclei and granular chromatin. Ependymomas were the only tumours with a fatal outcome (8 cases),
Myocardium presents ischemic areas. most of them were grade II and were equally located in the supra and
Conclusion: MS is a multifaceted disease related to HLA-DRB1 gene in the infratentorial space.
MHC class II region and environmentally to Epstein-Barr virus infection, Conclusion: Ependymal tumours have a highly variable clinical behav-
vitamin D deficiency and cigarette smoking.Prognosis centers on the quality iour. Our results match the literature highlighting that in children they are
of life and prospects for disability.Nowadays, there aren’t curative FDA- frequently located in the posterior fossa, and in this location complete
approved therapies for MS, though immunomodulator agents are used for resection is not always possible, leading to a higher chance of recurrence.
symptomatic relief. Future treatment may involve hematopoietic and mesen- Also, a lower grade does not warrant a better outcome, hence molecular
chymal stem cells.Genetic pathogenesis of BAC includes stepwise genetic sub-classification is expected to significantly support treatment decisions
hits, mostly K-ras, EGFR and HER2 mutations. Significant prognostic factors and help predict biological behaviour.
 Virchows Arch

E-PS-17-028 Background & Objectives: Rosette-forming glioneuronal tumour

Diffuse leptomeningeal glioneuronal tumour presenting with long (RGNT) is an unusual central nervous system (CNS) tumour more fre-
standing intractable seizure quently in young adults, with barely 150 cases reported. Nowadays,
L. Pal1, S. Katiyar2, A. Mehrotra3 RGNT is considered as a rare slow growing mixed glioneuronal tumour,
1
Sanjay Gandhi Postgraduate Institute of Medical Sciences, India, and it has been classified as a new CNS tumour in the 2007 WHO
2
Department of Pathology, Sanjay Gandhi Postgraduate Institute of classification. Before it has belonged to the group “rosette-forming
Medical Sciences, India, 3 Department of Neurosurgery, Sanjay Gandhi glioneuronal tumours from IV ventricle”. In 2016 those tumours have
Postgraduate Instute of Medical Sciences, India been renamed as “rosette-forming glioneuronal tumours” because other
locations have been reported (brainstem, pineal gland, thalamus).
Background & Objectives: Diffuse leptomeningeal glioneuronal tu- Methods: A 13-year-old boy with frontal headache and fever for months.
mours (DL-GNT) are uncommon neoplasms with recent acquisition in No other neurological symptoms were described. The magnetic resonance
WHO 2016 classification of central nervous system tumours and less than image (MRI) revealed a pineal tumour with triventricular hydrocephalus.
100 cases have been reported till date. DL-GNT is characterised by pre- Surgical resection of the tumour was performed in May 2018. After the
dominant and widespread involvement of the leptomeninges, oligoden- surgery, we received several irregular fragments that measures 2,1 x 2,3 cm.
droglial like cytology with evidence of neuronal differentiation. The vast Results: Histological examination showed areas composed by rounded
majority of DL-GNTs present as low-grade tumours, however, WHO cells with clear cytoplasm with round and monotonous nuclei located
grade has yet not been assigned due to less number of reported cases around capillaries, arranged as rosettes with fibrilar content. Other areas
and inadequate clinical follow up. DL-GNT are commonly encounterd showed fibrillar neuropilo with rounded cells that resembles
in children and mostly located in posterior fossa and spinal cord. oligodendrocites with loose mucoid areas. Rosettes and some tumour
However, we present two cases of this newly added entity located areas expressed Synaptophysin. Also stained positivity for glial fibrillary
supratentorially in adults. acidic protein (GFAP). IDH1 and p53 were both negatives. Ki67 index
Methods: The cases were retrieved from the institutional data base. After was< 1%.
routine histopathology, immunohistochemistry was performed on 3.5- Conclusion: RGNT is a biphasic tumour. The first component consists of
micron thick paraffin embedded sections using polymer based avidin- neurocites forming perivascular rosettes and/or pseudo rosettes. These
biotin peroxidase method. The primary antibodies used were GFAP, component is made up by astrocytes, resembling a pilocytic astrocytoma.
Vimentin, Neurofilament, NeuN, Synaptophysin, Ki-67, IDH-1, ATRX Clinical, radiological and immunohystochemial features of RGNT are not
and p53. Diaminobenzidine /H2O2 was used as substrate chromogen. well-defined, and current treatments and prognosis are hard to establish,
Results: Case 1: A 24-year-old male presented with left sided focal that indicate the need of further investigations. Despite the benign histo-
seizures for 5 years. Imaging revealed a large ill-defined mass in right logical grade, knowledge of the truly biology of this tumour remains
frontotemporal lobe of approximately 10x6 cm which was T1 unclear. Some papers have described aggressive behavior of RGNT as
hypointense and T2 hyperintense. Right fronto-temporal craniotomy recurrence and metastasis.
and gross total excision of the tumour was performed. On histopathol-
ogy, the tumour was seen diffusely infiltrating the leptomeninges with
presence of intraparenchymal nodules. Multiple cystic spaces of vary- E-PS-17-030
ing sizes filled with mucinous material were noted. These cystic spaces A parasagittal fibrous meningioma in a Sturge-Weber Syndrome
were surrounded by small oligodendroglial like cells. Mitosis / endo- patient
thelial proliferation /necrosis were not observed. Areas of astrocytic M. Alorjani1, S. Al Bashir1, S. Daoud1
1
morphology could also be appreciated. On immunohistochemistry, King Abdullah University Hospital, Jordan University of Science and
the tumour cells were variably positive for synaptophysin, vimentin, Technology, Jordan
GFAP and NeuN. IDH1 was negative. There was no ATRX mutation.
Ki67 index was ~2%. Case 2: A 50-year-old gentleman presented with Background & Objectives: Sturge–Weber syndrome (SWS) is a rare
multiple episodes of seizures for 16 years. MRI revealed well defined sporadic neurocutaneous disease, usually characterised by features in-
lesion in medial part of left temporal lobe. Histopathology showed cluding facial angiomas in the form of port-wine stain with ipsilateral
multiple foci of leptomeningeal tumour composed of bland leptomeningeal angiomatosis and choroidal angioma. Brain angiomas
oligodendroglioma like cells that were positive for GFAP, are thought to arise from a mutation in the guanine nucleotide-binding
synaptophysin and vimentin. Ki67 index was < 1%. IDH1 and ATRX protein G(q) subunit alpha (GNAQ), resulting in dysregulation of
were negative. Foci of calcification were also observed. Underlying endothelin, a G-protein coupled receptor, resulting in the vascular
brain parenchyma was involved focally. malformations found in SWS. Meningiomas in SWS patients have been
Conclusion: Diffuse leptomeningeal glioneuronal tumour was first de- described in only two case reports in the literature, both of intraventricular
scribed by Yamamoto et al as multifocal neurocytoma/gangliocytoma location; one of them was of psammomatous type and the second was
with extensive leptomeningeal dissemination in 1996. These tumours angiomatous. We report a parasagittal fibrous meningioma arising in a 30-
are commonly encountered in children and less frequently in adults. year-old male with SWS.
Both of our cases presented in adults, located supratentorially. Clinical Methods: A 30-year-old, man known to have SWS, with history of
behavior in reported series is not uniform and anaplastic changes has also epilepsy for the last 6 years. His seizure attacks worsened recently; a
been reported. As both our patients presented with long standing seizure reason for which he was investigated. CT scan in February, 2019 showed
with glioneuronal features immunohistochemically, probably indicates gyriform pattern of calcification in the left cerebral hemisphere with rel-
the diverse spectrum of this entity. atively reduced parenchymal volume (findings in keeping with the patient
history of SWS), with a large hypoattenuating area seen in the left
frontoparietal lobe. On MRI scan, there was a well-defined dural-based
E-PS-17-029 soft tissue mass in the left parasagittal parietal region, measuring 2.7 * 2.5
Rosette-forming glioneuronal tumour: a case report cm, in keeping with meningioma. The tumour was excised and sent to the
R.I. Bermudez Cameo1, H.P. Almanzar Comas1, A. Arellano Alvarez1, laboratory for pathological examination.
J.I. Franco1, M.J. Viso Soriano1, S. Bakali Badesa1, A. Sobrino Prados1, Results: Diagnosis: Fibrous meningioma, WHO grade I. The included
N. Estrada Mallarino1, J. Alfaro Torres1, I. Marquina Ibañez1, B. Roche portion of leptomeninges appeared thickened showing prominent dilated
Latasa1, M.F. Aznar Uson1, L. Hombria Laviña1, A. Valero Torres1 and thin vascular spaces along with increased cortical vascularity, features
1
Hospital Universitario Miguel Servet Zaragoza, Spain supporting the imaging findings of SWS.
Virchows Arch

Our case is diagnosed in a 30-year-old male with SWS, different Muenchen, Inst. Ethics (Dir.), Germany, 5 Univ. Lxbg. and Vienna, Fac.
from the two previously reported cases in location and type. Both Psychology (Dean), Austria, 6 Univ. Rostock, Inst. Physiology (Dir.a.D.),
of the other two cases were of intraventricular location; one was of Germany
psammomatous type in a 30-year-old female, while the other was
angiomatous in a 3-year-old boy. Background & Objectives: Neurology is essential clinical discipline
Conclusion: Meningioma has been rarely reported in association with for all health-sciences (medicine-psychology,etc.). An example for
SWS. It would be wise to investigate such rare cases of meningioma practical holistic& multidimensional psychoneuro-pathology is
arising in SWS patients for the GNAQ gene mutation (known in SWS given.
angiomas) to see if there is a shared mutation that may suggest a common Methods: Psychological items/electrical & motor-activities. Ref.: Neu,
pathway. Michailov et-al. 1-Pathology: ESP-2018-Bilbao, Eur.J.Pathol. 473/
Suppl.1:S180; ESP-2017-Amsterdam, Eur.J.Pathol. 471/Suppl.1:S245/
S284/S307;Int.Acad.Pathol./ESP-2016-Köln, Eur.J.Pathol. 469/
E-PS-17-031 Suppl.1:S245. 2-WFN-2016-Santiago-de-Chile, J.Neurol.Sci.357/S1,
Molecular imaging for automated tissue differentiation in high het- no.183,187,199,234). EAN-2015-Berlin Eur.J.Neurol.22/S1, p.281,487-
erogeneous tumours 490,832. 3-WPA-2018-Mexico-City (psychiatry), Abs.-Book WCP18-
V. Sergeeva1, A. Sorokin2, D. Ivanov2, V. Shurkhay3, P. Nikitin3, V. 0584/-0625/0643/0654. EPA-2019-Warschau (Eur.Psychiatry 56/S1,
Eliferov2, S. Pekov4, K. Bocharov4, I. Popov2 S689); 2018-Nice, Eur.Psychiatry 48/S1, S623&567&662. 4-[a]-
1
Emanuel Institute for Biochemical Physics, Russian Academy of IUPsyS-2012-Cape-Town, Int.J.Psychol 47:407; 2008-Berlin, 43/3-
Sciences, Russia, 2 Moscow Institute of Physics and Technology, 4:154,248,615,799. [b]-EFPA-2009 Oslo (psychology), 55-56. [c]-
Moscow, Russia, 3 N.N. Burdenko National Scientific and Practical IUPS-2017-Rio-de-Janeiro (physiology), AB:No. 997,999,1001,1003;
Center for Neurosurgery, Ministry of Healthcare of the Russia, 1977-Paris Proc13/1497-9; 1974-New-Delhi, Proc.11/273&378&1133.
4
V.L. Talrose Institute for Energy Problems of Chemical Physics, 5-SIU-2016-Buenos-Aires, WorldJ.Urol. 34/S1,126&223. 2007-Paris
Russian Academy of Sciences, Russia 70/S3A:232-3/2004-Honolulu Br.J.Urol. 94:24-5/258-9/305.
Results: A-PSYCHONEURO-PHYSIOLOGY. Probands-Patients
Background & Objectives: Implementation of mass spectrometry for (n=30, p<0.05-0.01): Physical education from Indian medicine incl.
molecular profiling allows automated malignant and intact tissue dif- Yoga (asanas & pranayamas): Voluntary apnoea/duration increase/10-
ferentiation in surgical samples. However, it requires the application 25%, respiratory rate/10-30% & heart rate decrease/5-10%. Effects aug-
of multi-criteria classifiers and regressors to overcome high natural mentation after 2 months/voluntary apnoea>100%, vital capacity>10%.
biological variability between samples. In this study, we apply Respiratory therapy/pranayama led to positive changes in psychic items:
MALDI-imaging mass spectrometry (MALDI-MSI) to high- relaxed-45%/tranquil-50%/clear-10%. Also Music therapy had positive
heterogeneous glial tumours in order to determine the spatial distri- item influence, relaxed-20%/tranqui1-5%/passive-25%/open-25%.
bution of lipids through the histological sample for improvement of Effects are stronger before surgical intervention (oncological patients)
tissue differentitation algorithms. then after this. B-Angio-Cardiological Psychoneuro-Pathology.
Methods: Stereotactic biopsy samples of glial tumours were (Patients-animals/n=20+25, p<0.05-0.01): Observations on patients
cryosectioned and covered with 2,5-dihydroxybenzoic acid by about pathophysiological reactions of bronchodilators & tocolytic thera-
sublimation. MALDI-images were obtained using Bruker py (ß-sympathomimetics) are conform with experiments: After buphenin/
ultrafleXtreme mass spectrometer in positive ion mode. Then, fenoterol adrenalin-contraction of rat aorta decreased,
the MALDI matrix was washed out, and slides were stained with cardiac&respiratory frequency in cats increased, blood pressure de-
H&E. creased. It appear EEG-patterns synchronization in cats (stereotaxically
Results: Major zones on each mass spectrometry image were determined implanted electrodes: hippocampus/hypothalamus posterior/nucleus
using nonlinear dimension reduction algorithm (t-SNE) application tractus solitarii). C-GENITO-UROLOGICAL PSYCHONEURO-
followed by k-means clustering. Each zone was classified accordingly PATHOLOGY. Neurological-gynaecological-urological patients
to the histological annotation of the sample, and characteristic mass spec- (cystotonometry/n=150, p<0.05-0.01): After radiochemotherapy
tra of each type of tissue were determined. Based on these spectra the (radiocystitis: Gamma- & X-irradiation-70Gy) vesical-tone increased,
multi-criteria classifiers and regressors for tissue differentiation were micturition-pressure & urothelial-electropotentials decreased.
constructed. Psychophysiological training (see A) counteracted functional distur-
Conclusion: Combination of MALDI-MSI and tissue staining is the only bances, acc.to B&C.
way to reliably determine the characteristic molecular profiles for high- Conclusion: Observations from A-C demonstrate example for an
heterogeneous tumours as it became possible to match each mass spectra integrative psychoneuro-pathology, i.e. application of practices
to exact tissue type. This information allows creating algorithms for tissue from clinical&experimental research in neurological education of
differentiation based on distinctive features combinations extracted from students (graduate&post-graduate) in context of UNO-Agenda21 for
characteristic spectra. Therefore it reveals the possibility for automated better health-education,etc. Interdisciplinary neurological observations are
pathological tissue differentiation in biopsy samples of glial tumours with reflected in ref.
high accuracy.

The work was supported by RSF #16-15-10431. E-PS-17-033

Neuropathology in context of anthropology and psychosomatics
M. Michailov1, E. Neu1, P. Birkenbihl1, T. Plattner1, B. Rattel2, T. Senn1,
E-PS-17-032 J. Foltinova3, C. Lütge4, M. Schratz5, G. Weber6
1
On an integrative psychoneuro-pathology: examples for neurological Inst. Umweltmedizin c/o ICSD/IAS e.V. München, 2 Amgen Res.
education and research Munich & IUM c/o ICSD/IAS e.V., 3 Univ. Bratislava, Med. Fac.,
E. Neu1, M. Michailov1, M. Bornhausen1, V. Foltin2, B. Rattel3, C. 4
Techn. Univ. Muenchen, Inst. Ethics, 5 Univ. Innsbruck, School Educ.,
6
Lütge4, G. Weber5, D.G. Weiss6 Univ. Lxbg. and Vienna, Fac. Psychology
1
Inst. Umweltmedizin c/o ICSD/IAS e.V. Muenchen, Germany,
2
St. Elisabeth Univ., Bratislava, Slovakia, 3 Amgen Res. Munich Background & Objectives: Neurology is fundamental discipline for
(Exec. Dir.) & IUM c/o ICSD/IAS e.V., Germany, 4 Techn. Univ. anthropological sciences – medicine, psychology upto biophysics/-
 Virchows Arch

chemistry. Future needs creation of an integrative neurology considering treatment. After surgical excision, the specimen was sent for histopatho-
holistic&multidimensional the human. Psychosomatics is essential for logical examination to the Department of Pathology of the Emergency
neurological therapy and prophylaxis. University Hospital in Bucharest
During Opening-Ceremony of 18th-World-Congress-Psychosomatic- Results: Specimen samples were fixed with 10% buffered formalin and
Medicine (ICPM-2005-Kobe) were present their majesties Emperor and were processed by conventional histopathological methods using paraffin
Empress of Japan, Prime&Ministers for Science-Education- embedding, sectioning and Hematoxylin–Eosin staining. We have also
others&prominent-scientists. Emperor AKIHITO honoured congress by performed immunohistochemical tests. Light microscopy examination
strategical ideas, “total symptoms of mind&body, seeking ways of holis- revealed a large-sized ciliary body melanoma consisting of heavily pig-
tic care… it is extremely important for patients … my hope contributes … ment spindle and epithelioid type cells (mixed cell type according to the
the progress of medical science and people's happiness in the entire modified Calendar classification). The posterior chamber of the eye was
world”. not affected but we observed multiple scattered malignant cells within the
Methods: Dedication for moral-scientific support of project: Austria: optic nerve, a very unusual feature.
K.Lorenz*, E.Busek, France: J.Dausset*, J.-M.Lehn*, Germany-GB: Conclusion: A comprehensive insight of the genetic, molecular and his-
M . E i g e n * , E . N e h e r * , H . M i c h e l * , B . Vo g e l , W. S c h e e l , topathological alterations in ocular melanoma can lead to an effective
J.&Th.v.Uexküll, GB: A.Hewish*, B.Josephson*, N.Tinbergen*, treatment. More information about drivers of uveal melanoma prolifera-
India-USA: D.Hubel*, H.G.Khorana*, L.Pauling*, K.Singh, Japan- tion and metastasis should be gathered from multiple trials. Ciliary body
USA: K.Fukui*, Y.Ikemi, S.Tonegawa*, Norway: D.Föllesdal, melanoma has a poor prognosis due to early metastases but in our case,
L.-R.Langslet, Russia: N.Basov*, A.Prokhorov*, A.Sacharow*, we emphasize the long-lasting evolution and peculiar anterior growth
Sweden: S.Bergström*, B.Samuelson*, South-Africa: Bishop pattern.
D.Tutu* (*Nobel Laureate).
Results: Conception Model for an integrative neurology related to
integral-anthropology based on physiological and pragmatic anthro- E-PS-18-002
pology from Immanuel KANT considers different “human-areas” Intravascular Kaposi's sarcoma of the bulbar conjunctiva in an im-
of human (“Integrationsebenen”), related to psychosomatic (Thure munocompetent patient
von UEXKÜLL) and somatopsychic theories (Yujiro IKEMI) is T.A. Georgescu1, A.C. Lisievici2, A. Dumitru2, L.M. Voinea3,4, M.
necessary. Somatic/psychical/mental/philosophical-spiritual, also Sajin2,5,6, M. Costache1,2
1
human interaction with nature&society (ref. see Neu et al. this Department of Pathology, Bucharest Emergency University Hospital,
congress). Romania, 2 Carol Davila University of Medicine and Pharmacy,
Conclusion: Foundation of International Academy for Neurology by Bucharest, Romania, 3 Department of Ophthalmology, "Carol Davila"
network of clinics from selected trans-European countries (America/ University of Medicine and Pharmacy, Bucharest, Romania,
4
Asia/others), similar to European-Acad-Neurology/EAN-2015- Department of Ophthalmology, Emergency University Hospital
Berlin, but enlarged scientific-organizatory principles such as com- Bucharest, Romania, 5 SUUB, Romania, 6 European Society of
mon personnel (similar to UNO-employees), honorary-permanent Pathology, Romania
directors, professors (meritocratic principle), possibility for whole
life working, scientist-participation from different disciplines (inter- Background & Objectives: Kaposi’s sarcoma (KS) is an uncommon
disciplinarity) could help for creation of integrative neurology spindle cell tumour of vascular origin, closely related to human her-
supporting UNO-Agenda21 for better health-education-ecology- pes virus 8 infection. It usually appears in patients with acquired
economy on global level. immunodeficiency syndrome (AIDS), immunosuppression or organ
transplantation. Most cases involve the skin, but mucosa, lymph
nodes and visceral organs can be affected as well. Conjunctival KS
Sunday, 8 September 2019 – Wednesday, 11 September 2019 is extremely rare and encountered mostly in patients with AIDS. It
E-PS-18 | Ophthalmic Pathology tends to be indolent, but, as the tumour grows, it can alter ocular
adnexal structures.
Methods: We report the case of a 60-year-old heterosexual male with
E-PS-18-001 unremarkable clinical history, presenting to the Department of
Ciliary body melanoma with optic nerve invasion and peculiar Ophthalmology of the Emergency University Hospital in Bucharest,
growth pattern Romania with a recently emerged mass in the bulbar conjunctiva of
A. Dumitru1, M. Costache1,2, M. Sajin3,4,5, T. Georgescu1 the right eye. Biomicroscopy revealed a dark red nodular lesion of
1
Department of Pathology, "Carol Davila" University of Medicine and 6/3 mm, in the lower nasal bulbar conjunctiva. The left eye revealed
Pharmacy, Bucharest, Romania, 2 Department of Pathology, Emergency no abnormalities. The patient was HIV negative, with no past or
University Hospital Bucharest, Romania, 3 SUUB, Romania, 4 UMF present lymphadenopathies or skin vascular lesions.
Carol Davila, Romania, 5 European Society of Pathology, Romania Results: After surgical excision, histopathological examination of the
nodule revealed a variably whorled proliferation of monomorphic spindle
Background & Objectives: The most common primary malignancy cells, featuring 4 mitoses per 5HPF, with slit-like vascular spaces and
of the eye in adults is the uveal melanoma. Frequently, uveal mela- extravasated erythrocytes, typical for KS. The nodule was completely
noma arises from choroid or iris. Ciliary body melanoma is a rare if surrounded by a thin vascular-like muscular wall, which was positive
not exceptional subtype of uveal melanoma being reported in 1 of 10 for SMA and desmin. Immunostaining for HHV8, CD34 and D2-40
cases of all intraocular melanomas. In this paper we will expose a revealed diffuse positivity across all tumour cells. The final diagnosis of
case report about a multinodular growth pattern of a ciliary body intravascular KS of the bulbar conjunctiva was established.
melanoma with optic nerv invasion and an unusual anterior Conclusion: Although conjunctival KS is rare in immunocompetent
extraocular extension. patients, the peculiarity of this case lies in its histopathological pre-
Methods: The patient, age 80, presented with permanent atrial fibrillation sentation as an intravascular tumour. To our knowledge, literature
and a large tumoral protrusion outside the left eye globe. After clinical data on intravascular KS is limited to a series of six cases, including
and imagistic re-evaluation, the patient was diagnosed with multiple he- both immunocompetent and immunocompromised patients. We be-
patic and lung metastases. The patient was firstly diagnosed with a small lieve that our finding may represent an extremely rare morphological
ciliary melanoma 10 years ago but at that time, she refused surgical variant of KS.
Virchows Arch

E-PS-18-004 Conclusion: Despite its rarity, any case of a child that presents an orbital
Eye and adnexa melanoma: experience of tertiary center involvement with osteolytic consequences may raise the suspicion of a
R. Almeida1,2, B. Pimentão1, H. Moreira1, J. Fraga1, A. Lai1, C. Faria1, V. Langerhans histiocytosis. The correlation between the particular histolog-
Almeida3, F. Ramalhosa1, R.C. Oliveira1, M.J. Julião1, M.A. Cipriano1 ical features and S100 protein/CD1a positivity of Langerhans cells, the
1
Centro Hospitalar e Universitário de Coimbra - Pathology department, clinical findings and the radiological images confirming the bone erosion
Portugal, 2 Faculty of Medicine in Coimbra, Portugal, 3 Institute of are considered adequate criteria for the diagnosis of the disease.
Anatomical and Molecular Pathology, Faculty of Medicine of the
University of Coimbra, Portugal
E-PS-18-006
Background & Objectives: Ocular melanoma is very uncommon, Orbital lymphoma
accounting for 5% of all melanomas, more common in white popu- G. Sahraoui1, N. Redissi1, R. Sellami1, L. Charfi1, R. Charfi1, K. Mrad1,
lations, rare in young people. It can develop de novo or from previous M. Driss1
1
naevi, and in some cases is not be possible to determine the precise Institut Salah Azaiez, Tunisia
primary anatomical location, particularly in advanced lesions.
Generally, the diagnosis is above 60y, there is no gender predilection, Background & Objectives: Orbital lymphomas (OL) are rare, compris-
and a considerable proportion of patients have no clinical manifesta- ing only 1% of all non-Hodgkin’s lymphoma. However, lymphomas are
tions. Those with symptoms can experience photopsia, loss of vision, the most common primary orbital tumour in adults 60 years of age and
redness or pain. older. Our study aimed to study the epidemiological and
Methods: We performed a retrospective research at Coimbra anatomopathological characteristics of OL.
Hospital and Universitary Centre, over a period of 10y (2009- Methods: We identified cases of OL diagnosed between January 2010
2019), and 18 cases of ocular melanoma were found. Then, we and December 2018.
performed a basic statistical analysis with clinicopathological Results: Our series included 9 cases of OL. The sex ratio was 1.2. The
correlation. average age was 51 years (3-71 years). Diagnosis was made on biopsies in
Results: Our sample included 18 patients, ages between 34y and 5 cases and on tumour exicion in 4 cases. Tumour was on the right side in 3
84y, 11 males and 7 females. Anatomical location: conjunctiva (4 cases, left in 2 cases and bilateral in 1 case. The side was not specified in the
cases), choroid (7 cases), ciliary body (3 cases) and orbit (2 cases); rest of the cases. All these lymphomas were phenotype B. The cells were
eleven cases were diagnosed through biopsy and nine in surgical small in 5 cases, medium in 1 case and large in 3 cases. Immunohistochemical
specimens; the median size of the tumours (among those 9 diag- study allowed to make the diagnosis of marginal zone lymphoma (MALT) in
nosed in surgical specimen) was 19,3mm, dimensions between 12 5 cases, follicular lymphoma in 2 cases, large B-cell lymphoma developed on
and 30mm. Morphologically, 11% were fusocelular (2 cases), 50% follicular lymphoma in 1 case and Burkitt lymphoma in 1 case.
were epithelioid (9 cases) and 39% had mixed pattern (6 cases). Of Conclusion: MALT lymphomas constitute the majority of orbital non-
the 9 patients submitted to surgical excision, only 1 relapsed in the Hodgkin’slymphomas. Clinical signs are unspecific. Surgical biopsy is
orbit, a case of a choroid melanoma, with extraocular extension of essential for diagnosis.
more than 5mm.
Conclusion: Ocular melanoma is associated with several characteris-
tic chromosomal anomalies and mutations in several genes: GNAQ, E-PS-18-007
GNA11, BAP1, SF3B1, and EIF1AX. In the following, we intend to Massive retinal gliosis in a young woman with congenital
perform some complementary studies, like BAP1 immunostaining, toxoplasmosis
associated with high risk of metastasis. This work pretends to add F. Pedica1, M. Callea1, N. Ahmed2, F. Sanvito1, C. Doglioni1,2
1
some knowledge about this uncommon malignancy in a more uncom- Pathology Unit, Division of Experimental Oncology, IRCCS San
mon location. Raffaele Scientific Institute, Milan, Italy, 2 Vita-Salute San Raffaele
University, Milan, Italy

E-PS-18-005 Background & Objectives: Massive retinal gliosis in a rare benign condi-
Orbital Langerhans cell histiocytosis: a challenging diagnosis tion characterised by a proliferation of non-atypical glial cells, called Müller
G. Sahraoui1, L. Bouzidi1, R. Doghri1, L. Charfi1, K. Mrad1, M. Driss1 cells, that affects the eye and has been described in association with several
1
Institut Salah Azaiez, Tunisia conditions, such as congenital malformations. We described a very rare case
of a young woman with a history of congenital toxoplasmosis.
Background & Objectives: Langerhans cell histiocytosis (LCH) is a rare Methods: Ayoung 25-year old woman underwent enuclation of the eye for a
disorder of mononuclear phagocytic system. It is often diagnosed in the painful microphtalmia, caused by congenital toxoplasmosis. The eye was
childhood. It primarily affects the skeletal system. Here we report a case tough and shrunken with a maximum diameter of cm 1,8 and a short segment
of a solitary orbital LCH to highlight its pathological features and remind of optic nerve of cm 0,2. On cut section the bulb was substituted by a calcified
its differential diagnosis. nodule of cm 1,2 in diameter. The whole tissue was examined.
Methods: A previously healthy 2-year -old boy presented with a 2-month Results: The eye architecture was completely subverted by the presence
history of diffuse left periorbital swelling. of a diffuse nodular proliferation of spindle-shaped cells organized in
Results: MRI of the orbit showed left orbital rim lesion with bony whorls, with mycrocystic areas, involving 80% of the bulb and replaced
destruction. Several diagnosis were discussed such as rhabdomyosar- the retina. These cells were immunoreactive for glial fibrillary acidic
coma, leukemia, lymphoma and neuroblastoma. Biopsy was per- protein (GFAP) and neuron specific enolase (NSE), partially for S100
formed. Microscopic examination showed a diffuse proliferation of and negative for melanin marker Melan-A. These cells were intermingled
mildly atypical cells resembling Langerhans cells, exhibiting vesicu- with thick vessels with hyaline wall and there was extensive bone marrow
lar and angulated nuclei, visible nucleoli with abundant cytoplasm, metaplasia. No mitosis were identified and the optic nerve was preserved.
associated with eosinophil, lymphocyte, and macrophage. Conclusion: We concluded that this was a very rare case of massive
Immunohistochemistry was positive for protein S-100 and CD1a retinal gliosis developed in collapsed shrunken eye because of a congen-
and negative for CD20, CD3, CD 30, Chromogranin, ital toxoplasmosis. To our knowledge this is a very rare case and, since
Synaptophysin, myogenin, desmin and CD68. Hence, a diagnosis this is a mass-forming lesion growing inside the eye, histology is neces-
of LCH was made. sary for diagnosis.
 Virchows Arch

E-PS-18-008 undifferentiated sarcoma in two cases and histiocytic sarcoma in

Mixed choroidal melanoma of the left eye - a case report and review one case with pleomorphic lesional cells with abundant granular
of the literature eosinophilic cytoplasm, large oval or round nuclei with prominent
N.J. Lamas1, M. Oliveira1, L. Ferreira1, C. Fleming1, R. Amorim2, J.R. nucleoli, and occasional infolding of nuclei. Imunohistochemistry
Brandão2, B. Fernandes2, J.R. Alves1, J.R. Vizcaíno1 reveal vimentin positivity in all cases and CD68 positivity in
1
Anatomical Pathology Service, Department of Pathology, Hospital and histiocytic sarcoma. All the other antibodies were negative.
University Center of Porto, Porto, Portugal, 2 Centro Hospitalar do Porto, Tumour recurrence occurred in two cases. A complement of ex-
Portugal ternal radiotherapy was performed in one case and surgical exen-
teration in another case.
Background & Objectives: Melanoma of the uvea is the most frequent Conclusion: Conjunctival sarcoma are very rare malignancies that
intraocular malignant tumour in adults with an estimated incidence of we must consider in front of any conjunctival mass. Poor prog-
nearly 5 cases per million per year. Almost 90% of the tumours are nosis is often related to the diagnosis delay and insufficient initial
located in the choroid. The long-term survival for patients with uveal surgical excision.
melanoma is conditioned by the risk of metastasis, especially to the liver.
Methods: We report the case of a 77-year-old male with complaints
of unspecific visual changes lasting for 4 months. The left eye exam- E-PS-18-010
ination revealed a bulky pigmented lesion associated with retinal Orbital location of Langerhans cell histiocytosis: clinical aspect and
detachment. The right eye was unremarkable. The patient had a di- histological features
agnosis of skin melanoma 10 years before, without further recur- N. Boujelbene1, A. Rouatbi2, I. Abbes1, L. Charfi1, R. Doghri1, N. Ben
rence; and a previous history of multiple skin basal cell carcinomas. Hamida1, H. Guizani1, K. Mrad1, M. Driss1
1
Enucleation of the left eye was performed. Department of Pathology, Salah Azaiez Institute, Tunisia, 2 National
Results: An eye specimen weighing 10g was received, comprising a Eye Institute of Tunis, Tunisia
3x2,8x2,8cm ocular globe, with a 1,9x1,2cm cornea and a 0,3cm optic
nerve segment. Upon section, in the posterior area of the posterior cham- Background & Objectives: Orbital location of langerhans cell
ber, we observed a neoplasia measuring 2,5cm (thickness) x 2cm (largest histiocytosis (LCH) is a rare entity usually affecting the child or young
basal diameter), with well-defined limits, elastic consistency and heavily adult. The diagnosis is often difficult based on the lesional biopsy. Here
pigmented (dark brown). The morphological study revealed a solid neo- we present four cases of orbital LCH with emphasize clinical presentation
plasia composed by both fusiform and epithelioid cells, with nuclear and histological features.
pleomorphism and frequent mitosis. Intense cytoplasmic brown pigment Methods: A comprehensive ophthalmological and general exam were
was observed focally. The neoplasia was permeated by a sparse lympho- performed in all cases. Orbital imaging (computed tomography or mag-
cytic inflammatory infiltrate. The estimated proliferative index (%Ki-67) netic resonance imaging) and orbital biopsy were performed in all cases.
was nearly 40%. The neoplasia did not involve the ciliar body, retina, Results: Two men and two women were followed. Respectively
optic nerve, vitreum, iris, lens, Schlemm channel, sclera and cornea. The aged 6, 20, 23 and 46 years old. All four patient presented with
diagnosis of mixed melanoma of the choroid was made. Additional pos- acute exophthalmos. Rapid growth was noted in two cases.
itron emission tomography (PET) scan studies did not reveal metastasis. Blurred vision was noted in 3 cases. Orbital imaging showed
Conclusion: This case illustrates the main features of these rare lesions, diffuse orbital tumour in all cases with orbital osteolysis in one
which might display aggressive behaviour. The metastasis risk signifi- case. Orbital incisional biopsy was performed in 3 cases and
cantly increases for lesions having largest basal diameters above 0,3mm. excisional biopsy in one case. Histologic features included numer-
Thus, a long-term follow-up of the patients is mandatory. ous histiocytes with varying degrees of giant cell (GC) formation
and scattered eosinophilic granulocytes (EG). Langerhans cells
was confirmed by CD1a and S100 immunostaining. The diffuse
E-PS-18-009 character of the orbital invasion enabled excisional resection in 3
Primitive conjunctival sarcoma: clinical and histological features of cases. We there for performed systemic chemotherapy in 3 cases
three consecutive cases with systemic corticosteroids in one case. Complete regression of
N. Boujelbene1, A. Rouatbi2, L. Charfi1, R. Doghri1, I. Abbes1, N. Ben the orbital lesion was achieved in all cases with no recurrence
Hamida1, K. Mrad1, M. Driss1 after a mean follow up of 18 months.
1
Department of Pathology, Salah Azaiez Institute, Tunisia, 2 National Conclusion: GC and EG should alert the pathologist to perform adequate
Eye Institute of Tunis, Tunisia immunohistochemistry. The clinical course of LCH is variable and the
therapeutic response generally favorable.
Background & Objectives: Primitive conjunctival sarcoma are rare ma-
lignancies. There has been a significant recent rise in the reporting of
ocular and ocular adnexal sarcomas in association with acquired immu- E-PS-18-011
nodeficiency syndrome, and irradiation of the orbits of children with Pathological prognostic factors in retinoblastoma: a study of 85 cases
hereditary retinoblastoma. We describe clinical, histological and immu- in Tunisian children
nohistochemical features of three cases of conjunctival growth with sar- N. Boujelbene1, I. Abbes1, R. Doghri1, L. Charfi1, R. Ben Ghorbel1, D.
comatous histological appearance. Kacem1, K. Mrad1, M. Driss1
1
Methods: Three consecutive cases were described. Conjunctival Department of Pathology, Salah Azaiez Institute, Tunisia
growth was present in all cases. Orbital imaging and excisional bi-
opsy were performed in all cases. Immunohistochemical stains in- Background & Objectives: Retinoblastoma is the most common
cluding Vimentin, CD68, PS100, CD34, Desmin and Cytokeratin primary intraocular malignancy of childhood representing 3% of
was performed. all childhood cancers. The main therapeutic priority for retinoblas-
Results: Two men and a woman aged respectively of 38, 56 and toma is to first save the child’s life through early tumour detection
76 years old consulted for an expansive conjunctival process of a and prevention of metastatic spread. We aimed to assess histopath-
mean of one month duration. Clinical course was rapid in two ological factors in a series of children and to determine the most
cases with orbital extension in one case. An excisional biopsy significant histopronostic factors in terms of risk recurrence, me-
was performed in all cases. Histological examination revealed tastasis and death.
Virchows Arch

Methods: We retrospectively analysed the data of consecutive children with progressive edema and dystrophic changes in the cornea. The
diagnosed in our hospital between 1993 and 2009 as having retinoblas- aim was to evaluate the changes of CD44, MMP9 and TGFβ1 ex-
toma. For bilateral cases, only the most affected eyeball was included in pression in corneas with CED after HA injections.
the study. After pathological confirmation of the diagnosis, histological Methods: The study was performed on the surgical material of 14
risk factors were noted. Survival curves were performed by the Kaplan- corneas explants: healthy corneas, secondary CED, Fuchs' corneal
Meier and Cox regression methods. endothelial dystrophy (FECD), lattice corneal dystrophy, type I
Results: A total of 76 cases of retinoblastoma were included. (LCED). Expression of CD44, MMP9 and TGFβ1 was assessed
Retinoblastoma has a good prognosis (overall survival rate at 2 years = by morphometric analysis (Aperio ImageScope and WCIF
91.4%). In multivariate analysis, bilaterality and infiltration of the sec- ImageJ).
tional section of the optic nerve were independent predictors of death. In Results: Expression level of CD44 was significantly higher in CED
univariate analysis, large size, massive choroid invasion, extra-scleral group then in normal tissues (p=0,03) and in secondary CED group
invasion, and invasion of the optic nerve section were significantly asso- then in hereditary CED, (р˂0,001). CD44 expression was significant-
ciated with high rates of death and metastasis. Invasion of the anterior ly higher in LCED then in FECD. Expression of MMP9 in corneal
chamber, extensive necrosis, invasion of the subarachnoidal space, and epithelium and keratocites was lower in CED group (p=0,03 and
laminar and pre-laminar invasion of the optic nerve were not associated p˂0,001 respectively) then in normal tissues. In hereditary CED
with a poor prognosis. group level of MMP9 expression was significantly lower then in
Conclusion: For optimal therapeutic management, it is necessary to control and secondary CED groups. Expression level of TGFβ1was
insist on the collaboration between the pathologist and the clinician higher in LCED group then in secondary CED, FECD (p=0,033) and
for a better precision and taking into consideration the histopronostic control groups (p˂0,001). After HA subconjuctival administration: 1)
factors. CD44 expression decreased in FECD group; 2) MMP9 epithelial and
stromal expression levels decreased in secondary CED and FECD
group; 3) TGFβ1 expression level decreased in epithelium in
E-PS-18-012 LCED and keratocites in secondary CED groups.
Conjunctival melanoma Conclusion: Injections of hyaluronic acid allow to achieve clinical
R. Narjess1, N. Boujelbene2, M. Driss2, R. Doghri2, I. Abbess2, H. Arbi2, effect in CED treatment, accelerates CD44 associated regeneration,
K. Mrad2, L. Charfi2 decrease propoptotic effect TGFβ1 in corneal epithelium, MMP and
1
Institut of Carcinology Salah Azaiz Tunis, Tunisia, 2 Department of TGFβ1 mediated remodeling of corneal stroma.
Pathology, Salah Azaiez Institute, Tunisia

Background & Objectives: Invasive melanoma of the conjunctiva ac- Sunday, 8 September 2019 – Wednesday, 11 September 2019
counts for 2%–5% of ocular malignancies. It is potentially deadly tumour E-PS-19 | Other Topics
despite progress and therapeutic advances in the management. The aim of
this study was to undertake a retrospective analysis of the prognostic
factors for conjunctival melanoma. E-PS-19-001
Methods: Demographic and clinicopathologic features including: lo- Pure de-novo 4.5 Mb duplication at Xp11.22-Xp11.23 in an 18-
cation, tumour thickness, ulceration, mitotic rate, histology, month-old boy: phenotypic and molecular characterisation
lymphovascular invasion and association of primary acquired D. Jovanovic1, N. Breland1
1
melanosis were reviewed. Trinity School of Medicine, USA
Results: Our study identified 13 cases including 9 men and 4
women. The average age was 63 years old. The samples consist Background & Objectives: In males pure duplications of the short
of excision specimens in 7 cases, 4 of which were incomplete, arm of chromosome X are rare, in most cases are inherited from a
biopsies in 6 cases and one case of complete exenteration. The heterozygote mother. We report here phenotypic and molecular
tumour was localized on the bulbar conjunctiva in 8 cases and in characterization of a de-novo 4.5 Mb duplication at Xp11-22-
non-bulbar conjunctiva in 5 cases. The average thickness of the p11.23 in an 18-month-old boy with hypotonia and developmental
tumour was 3.8 (range from 1 to 13 mm). In 3 cases we noted delay.
the presence of a primary acquired melanosis. The average number Methods: Single nucleotide polymorphism was performed using the
of mitoses was 4 (1 to 15 mitotic figures per ten high-power Affymetrics Cytoscan HD platform applying the probes having me-
fields). None of the specimens had a vascular embolus, ulceration dian spacing of 0.88 kb. With NspI digested patient’s genomic DNA
or necrosis. The extension assessment was negative in all cases and was ligated to NspI adaptors and amplified using Titanium Tag with a
3 of the patients presented a local recurrence of which one pre- GeneAmp PCR system 9700. Purified fragmented biotin labeled
sented 3 recurrences. DNA was hybridized to the HD gene chip. Data was analysed using
Conclusion: Conjunctival melanoma is a very rare malignancy. The tu- Chromosome Analysis Suite. Maternal FISH analysis was used to
mour typically presents with a rapidly progressive, well defined mass that determine inheritance pattern.
is, in some cases, amenable to macroscopically intact excision. The pre- Results: The patient is unable to utilize the large muscle systems in his
cision of the various histological prognostic factors is important to guide body to move from place to place, assume a stable posture when moving,
the therapeutic management. and to raise self to a standing position. He is not yet saying words.
Chromosome microarray test found Xp11.23-p11.22 (48,237,630-52,
737, 268) x2 including numerous OMIM genes (start: SSX4 to end:
E-PS-18-013 SSX7) and SHROOM4. Maternal FISH analysis did not detect duplica-
Patterns of biomolecular markers expression in patients with corneal tion of Xp11.23.
endothelial dystrophies before and after injections of hyaluronic acid Conclusion: The patient has a large duplication containing multiple
V. Zakharava1, G. Semak1, I. Zherka1, T. Liatkouskaya1,2, S. Kletski1 genes many of which are important for normal development. Many
1
Belarusian State Medical University, Belarus, 2 ESP, Belarus children have speech delay, cognitive deficits, sleep disorders and
epilepsy. Since Mom does not have the duplication she can not pass
Background & Objectives: Corneal endothelial dystrophy (CED) is it on to other children. This is de novo change for our patient not
associated with primary non-inflammatory damage of endothelium caused by anything that occurred during pregnancy.
 Virchows Arch

1
E-PS-19-002 Basic Nursing, Health Science, Hamamatsu Univ School Med, Japan,
2
Primary gestational fallopian tube choriocarcinoma arising in dizy- Department of Diagnostic Pathology, Shizuoka City Hospital, Japan
gous twin pregnancy
J. Wright1, W. Hamarneh1 Background & Objectives: Acoustic parameters of speed-of-sound and
1
Northwick Park and St. Mark's Hospital, United Kingdom attenuation-of-sound correspond to tissue stiffness and viscosity. If spe-
cial materials bind to nucleus, conformational change may occur to effect
Background & Objectives: Choriocarcinoma is an incredibly rare and on acoustic properties. We tried to investigate anti-cancer drugs such as
malignant subtype of gestational trophoblastic disease that may coincide cisplatin and arsenic solution to alter nuclear images of histology sections
with normal, molar or ectopic pregnancies. Choriocarcinoma associated after incubation.
with ectopic pregnancy has an incidence of 1.5/million. Fallopian tube Methods: Acoustic images of cytology and tissue slides were observed to
choriocarcinoma is most frequently gestational, and is associated with be compared before and after incubation by scanning acoustic micro-
serious morbidity, as by the time of diagnosis, metastasis is highly likely scope. For anticancer drugs, cisplatin and arsenic solution were used.
due to rupture of the tubal wall into the pelvic cavity. Acoustic images were compared with the corresponding light microscop-
Methods: We report a case of primary gestational tubal ectopic choriocar- ic (LM) images.
cinoma that ruptured and metastasised to the lungs, arising in a dizygous Results: AOS and SOS values of nuclei increased after incubation with
twin pregnancy, where the intrauterine foetus was successfully delivered. cisplatin. Fresh tissues showed more conspicuous changes compared with
Results: A 37-year-old pregnant female, who was fit, developed inter- FFPE sections. On the contrary, arsenic solution revealed no remarkable
mittent abdominal pain at 19/40. At 34/40 weeks she presented acutely to changes. The corresponding LM images displayed no apparent changes
our regional centre. Pelvic ultrasound suggested an ovarian torsion. before after incubation.
Histology revealed choriocarcinoma within fallopian tube. Normal pla- Conclusion: Acoustic microscope can detect cisplatin distribution on the
centa, omental deciduosis and benign peritoneal fluid cytology. nuclei to induce conformational changes.These changes were not detect-
CT Pulmonary Angiogram demonstrated bilateral lung nodules confirmed ed by LM.
histologically as metastatic choriocarcinoma. Post-operatively, the patient
recovered well and commenced chemotherapy at a specialist trophoblastic Supported by Japan Society for the Promotion of Science (KAKENHI),
unit. The metastatic deposits disappeared, and the patient is still alive. Scientific Research Grant Number (c) 15K08375.
Conclusion: Primary gestational fallopian tube choriocarcinoma is ex-
tremely rare, and should always be considered whilst examining ectopic
pregnancy specimens. To our knowledge, this is the first report of such E-PS-19-005
case occurring as part of a dizygous twin pregnancy. Modulated electro-hyperthermia enhances doxorubicin efficacy in
colorectal adenocarcinoma in vitro
T. Vancsik1, E. Kiss1, G. Forika1, A. Balogh2, T. Krenacs1
1
E-PS-19-003 Department of Pathology and Experimental Cancer Research,
Clinicopathologic features of rheumatoid nodule: a study of 57 cases Semmelweis University, Hungary, 2 Institute of Clinical Experimental
B. Seong Sik1, S. Su-Jin1, J. Kiseok1, P. Seung Sam1, K. Yeseul1 Research, Semmelweis University, Hungary
1
Department of Pathology, College of Medicine, Hanyang University,
Republic of Korea Background & Objectives: Modulated electro-hyperthermia (mEHT)
is a non-invasive complementary treatment to radio- or chemother-
Background & Objectives: The clinical and histopathologic features of 57 apy which can induce selective cell stress and heat shock at ~42oC
cases that have been diagnosed with rheumatoid nodules were investigated. in tumour tissue. Here we studied the molecular background of
Methods: This study included 57 cases of rheumatoid nodule confirmed by mEHT mediated tumour damage and its combination with the topo-
histologic assessment between 2005 and 2018 at Hanyang University isomerase inhibitor and DNA-intercalating doxorubicin treatment
Hospital. According to the American College of Rheumatology (ACR) in vitro.
criteria, only patients with a total score of 6 or more were included, patients Methods: Coverslip cultures of C26 mouse colorectal adenocarcino-
of lack of evidence of rheumatoid arthritis were excluded. The clinical data of ma cell line were treated with mEHT at 42oC (2x60 min with 120 min
all patients were obtained from electronic medical records. Clinical impres- breaks) alone or in combination with 1 μM doxorubicin (mEHT+
sion and imaging assessment before histologic diagnosis were also collected. Dox). Stress response, cell death, apoptosis and proliferation related
Results: The median age of the patients at the time of diagnosis was 57 years. markers were detected using immunocytochemistry and qPCR;
Most of them showed high-positive rheumatoid factor (RF) or high-positive anti- complemented with resazurin viability assay, flow-cytometry for cell
citrullinated protein antibodies (ACPA), a few patients showed low-positive RA or death response and clonogenic assay for counting cancer progenitor
low-positive ACPA. The most common anatomical location was the foot. In all cells.
cases, the central necrobiosis was present, and the necrobiosis contained neutrophils Results: MEHT induced significant hsp70 and calreticulin protein release
and nuclear debris. The palisading of histiocytes, perivascular lymphocytic infiltra- (24h) and reduced the tumour stem-cell colonies (10-days). Significant
tion, stromal fibrosis, cleft or cystic degeneration were observed in many cases. decrease of anti-apoptotic XIAP, BCL-2, BCL-XL, and elevation of pro-
Conclusion: In this study, we reviewed the clinical, imaging, and histologic apoptotic BAX, PUMA mRNA levels were detected, besides increased
features of 57 patients diagnosed with the rheumatoid nodule. The clinico- P21 rates. Between 24-48h mEHT progressively reduced of tumour cell-
pathological review of cases diagnosed with rheumatoid nodule histologically viability by apoptosis what was increased after mEHT+Dox combination,
was performed to confirm the characteristics that can help to understand the while Dox dominantly induced necrosis. Nuclear phospho-p53(Ser15)
pathophysiology and make an accurate diagnosis of the rheumatoid nodule. protein levels were significantly increased in all treated groups, while
phospho-Akt(Ser473) levels were reduced but only after mEHT and
Supported by governmental grants. mEHT+Dox.
Conclusion: MEHT can induce apoptotic cell-death and inhibition of
tumour-cell proliferation in colorectal adenocarcinoma, possibly linked
E-PS-19-004 to p53 activated p21waf1 upregulation and the concomitant reduction of
Nuclear structure alteration after anti-cancer drugs incubation by active Akt protein, which could normally inhibit p53 functions. This
acoustic microscopy mEHT induced mechanism could potentiate the cytotoxic effect
K. Miura1, K. Yamashita1, Y. Egawa2, T. Moriki2 doxorubicin.
Virchows Arch

This study was funded by NKFIH-NVKP_16-1-2016-0042 and also sup- Methods: We assessed technical quality of block processing, and slide
ported by EFOP-3.6.3-VEKOP-16-2017-00009 predoctoral grant. cutting by histotechnologists and quality of H+E staining, special and
immunohistochemical stains by pathologists with a standard input form.
2500 specimens were dissected and split by 2 PAs. 3 parts scheme with
E-PS-19-006 free text comments used for histology assessment (High, Average, Low
Human identification using molecular techniques based on genetical- Quality) and pathologist’ microscopic evaluation (Acceptable, Inferior,
ly variant peptides Unacceptable for diagnosis).
D. Anestakis1, M. Psallida1, E. Chatzifotiou1, F. Louka1, P. Pavlidis2, N. Results: The study validates the technical, H&E and immunohis-
Raikos1 tochemical stain quality obtained with a the generation
1
Department of Autopsy Histopathology, Lab. of Forensic Medicine and tissueprocessor Donatello Serie 2. The experienced benefits tested,
Toxicology, Aristotle University of Thessaloniki, Greece, 2 Lab. of in comparison with standard tissueprocessors, in terms of process-
Forensic Medicine, Medical School, Democritus University of Thrace, ing quality, are enhanced by the addition of various technical
Greece improvements, as the selfcheck technology, that dramatically re-
duce the the incidence of adverse events and overnight
Background & Objectives: While time goes by, human body tissues and tissueprocessor errors and the reagent replacement system, that
cells change, decay and are led to death. The way of death plays an allows to easily and safely replace reagent and paraffin, avoiding
important role in human identification, because of the difficulties in sam- mistakes and spillages.
ples’ microscopic examination. If the body is found either in very ad- Conclusion: After five months and more than 2000 samples processed,
vanced sepsis or burned, even if the only remain is a skeleton or a bone, morphology evaluation on both standard HE and IHC, the results con-
without tissue, analyzing the samples may be troubling. firms that Donatello 2 can be used as standard tissue processor in any
Methods: In many cases such as these, there is no way to extract DNA, or pathology lab, with all the benefits previously listed.
even if it is, there may be many contaminations and alterations during the
processing. To overcome these dangers, there is an analyzing method
using peptides, which are extracted in different ways comparing with E-PS-19-009
DNA. During bone identification, there can be Genetically Variant A 5-year retrospective study of extracutaneous melanomas
Peptides (GVPs) extracted from it. B.R. Nataras1, A. Dema2, C.D. Lazureanu1,3, D. Herman2, S. Taban1,3,
Results: In the first step, Single Amino acid Polymorphisms and M. Cornianu1,3, D. Szilagyi1, A. Muresan1,4, S. Costi1, I. Uglai1, S.C.
Single Nucleotide Polymorphism alleles are extracted, so they can Suciu1,3, D. Anderco1, M. Iacob5
1
be analysed with Mass Spectrometer and compared with polymor- Emergency Clinical County Hospital ''Pius Brinzeu'' Timisoara,
phism databases . These Genetic Variant Peptides will be put in like- Romania, 2 Department of Pathology, Emergency Clinical County
lihood ratios and according to them they will be matched in the first Hospital "Pius Brinzeu", Timisoara, Romania, 3 ''Victor Babes''
place with population groups and in the second place with a single University of Medicine and Pharmacy Timisoara, Department of
person in this group. Pathology, Romania, 4 ''Victor Babes'' University of Medicine and
Conclusion: This is a high deficiency method, which has many advan- Pharmacy'' Timisoara, Department of Pathology, Romania,
5
tages comparing with others due to the contamination restriction. It uses Department of Pathology, Emergency County Hospital Timișoara,
polymorphisms and databases, so there is a limitation-prohibition of the Romania
false-positive results. This method can be also used in other tissues as well
as in combination with other techniques it can cover a large field in Background & Objectives: Diffuse chorionic haemosiderosis (DCH) is
forensics. an abnormality of the placental membranes, characterised by the deposi-
tion of iron pigment. It is usually secondary to recurrent venous bleeding
from early pregnancy. In many papers, it is associated with pre-term
E-PS-19-008 delivery. Fetal vascular malperfusion (FVM) is an abnormality of the
Validation of histology tissue processing fetoplacental circulation that may be seen at any gestational age, but often
P. Locatelli1, S. Caboni1, F. De Angelis1, F. Pellegrino2, C. Lupo3 in the third trimester. No link has been identified in the placental literature,
1
LaboPath Diapath S.p.A, Italy, 2 SAMAR Medical Center, Rome, Italy, but we have noted the two conditions co-existing. This study examined
3
Innovation Department, Diapath Headquarter, Italy the association of these two entities.
Methods: Laboratory records were searched for singleton cases diag-
Background & Objectives: The increasing incidence of disease, es- nosed as DCH on H&E stain over a 5-year period. These were classified
pecially cancer, has been the major driver of tissue processing quality as showing high-grade FVM (HGFVM), low-grade FVM (LGFVM) or
into the diagnostics workflow. A proper processing confers quality to no FVM. Controls were gestational-matched cases without DCH. Cord
the tissue and preserves morphological and molecular information, length, coiling, insertion, or other abnormalities were noted. Membranes
very important for diagnostic purposes. Losing information during were classified as normal or circumvallate. Results were analysed using
processing prevents a correct diagnosis, so the possibility of associ- Graphpad.
ating the correct oncologic target therapy, even leading to therapeutic Results: There were 66 cases of DCH between 16 and 41 weeks gestation
failures. To prepare samples for diagnosis, with automatic tissue pro- and 130 controls. 14/66 (21%) cases of DCH showed HGFVM and 2/66
cessors, the common machines in the market use up to 12 different (3%) showed LGFVM. 16/130 (12%) controls showed HGFVM and 20/
tanks of chemicals (formalin, alcohol, xylene and paraffin) and 4-5 130 (15%) had LGFVM. Where FVM is present, high-grade FVM is
litres each are used: this poses a huge problem in the disposal of the significantly associated with DCH versus controls (P<0.0031 Fischer’s
waste chemicals, significant costs for the operator and the environ- Test).
ment and the risk for samples due to possible failures in each step Conclusion: HGFVM occurs significantly more often in placentas with
during the tissue processing. Another key issue in this process is DCH. Histologic correlates of FVM have been under-explored to date.
about the formalin, the first chemical used during the process, that We have previously shown that FVM occurs four times more commonly
guarantees the preservation of cellular morphology. The purpose of in placentas with maternal vascular malperfusion (MVM) (Cooley et al
this work is to validate a next generation tissue processor (Donatello JOG 2011). Both FVM and DCH are among 9 lesions significantly in-
Series 2) with aims to: 1) integration of the tissue processor into creased in placentas from infants with neurologic injury, and both are
workflow process, 2) evaluate specimen quality. independently related to neurologic injury (Redline & ORiordan Arch
 Virchows Arch

Pathol Lab Med 2000). Whether iron in high quantities causes or contrib- ColV were markedly elevated in AI-24h. The occurrence of high levels of
utes to vascular damage in the developing placenta requires further study. AB against ColV was associated with the early stage of disease
characterised by histologically documented inflammation and coincided
with significant increase of ColVand decrease of Collagen I largely in the
E-PS-19-010 pericellular matrix of synovia.
Oncomine comprehensive cancer panel analysis of metastatic mela- Conclusion: The results suggest that AB to ColVoccur as a consequence
noma for two year experience of tissue destruction and an evidence for a pathogenetic role of this im-
H. Kim1, K. Jang1, J. Lee2 munogenic collagen in rat arthritis thus emerging as a promise biomarker
1
Department of Pathology and Translational Genomics, Samsung of early detection of fibrosis.
Medical Center, Republic of Korea, 2 Division of Haematology-
Oncology, Department of Medicine, Samsung Medical Center, Supported by FAPESP, CNPq, LIM.
Sungkyunkwan University School of Medicine, Seoul, Republic of
Korea
E-PS-19-012
Background & Objectives: Next-generation sequencing (NGS)-based Aberrant isotopic composition of tumour environment in growing
cancer panel test can be applied in precision oncologic medicine for 'in vivo' cancers in developmental age
refractory metastatic melanoma. Here, we summarized our two-year K. Taran1, P. Paneth2
1
experience of Oncomine comprehensive cancer panel test for Medical University of Lodz, Poland, 2 Lodz University of Technology,
melanoma. Poland
Methods: From January 2017 to December 2018, 85 cases of metastatic
melanoma were sequenced. After histological assessment, macrodissection Background & Objectives: Current efforts in understanding of cancer
of tumour areas in formalin-fixed paraffin-embedded sections was per- biology have focus on the evolving interplay between the tumour cells and
formed followed by DNA extraction, NGS, and analysis using an their environment. It was proved that connective tissue surrounding tu-
Oncomine knowledgebase reporter. mours brings substrates for further anabolism. Although a passive role of
Results: The average mapped reads were 8,826,878 and that of tumour fatty tissue is mostly recognized it may also act as the key organ of ho-
purity, mean depth, ontarget and uniformity were 65.28%, 3624.5, meostasis able to evoke systemic effects. The highest credibility of Isotope
97.75% and 89.43%, respectively. In quality score, 81 out of 85 cases ratio Mass Spectrometry proved in forensic, makes the method a perfectly
revealed good or very good. In Tier I class of SNV/Indel, 16(18.82%) precise tool ffor as deep and effective histoanalysis, which seems to be
BRAF and 10(11.76%) NRAS were noted with no CNV and any fusion. especially desirable in complex and hardly known tumour environment.
In Tier II class, SNV/Indel of 7 genes were noted overlapped. In Tier II of Methods: We took an advanced Continuous Flow IRMS coupled with
CNV, 13 genes were noted overlapped. elemental analyser to create 48 isotopic profiles of morphologically un-
Conclusion: NGS-based cancer panel test using FFPE can be applied changed cancer environment (connective and fatty tissue) as well as of the
in precision oncologic treatment. Although detected genetic alter- same tissues from healthy individuals obtained in post-mortem examina-
ation of Tier I and II class was relatively small, we suspect NGS- tions to search for potential differences.
based genetic analysis will provide more actionable targets in mela- Results: Isotopic signatures of nitrogen and carbon appeared different in
noma treatment. tissues from healthy individuals and cancer patients, appropriately.
Unexpectedly, both tissues from tumour environment - fatty tissue the
same as connective tissue showed isotopic profiles on average nitrogen
E-PS-19-011 enriched and carbon depleted.
In situ and humoral sensitivity to native type V collagen in early Conclusion: Our findings highlight connective tissue as the most univer-
synovial fibrosis of a rat model of arthritis sal source of heavy nitrogen giving natural support to arising and growing
L.K. Ramos da Silveira1,2, A.P. Pereira Velosa3, S. Catanozi1,4, A. Santos cancer cells. Furthermore, they may indicate an important role of fatty
Filho3,2, S. Fernezlian1,5, E. Eher1,5, J. Tomaz de Miranda1,2, V.L. tissue in metabolic and homeostatic support during according to changing
Capelozzi1,6, W. Rosolia Teodoro1,2 demands of the tumour cells during cancer expansion.
1
Faculdade de Medicina, Universidade de Sao Paulo, Brazil,
2
Rheumatology Division, Brazil, 3 Hospital das Clinicas HCFMUSP,
Faculdade de Medicina, Universidade de Sao Paulo, Brazil, E-PS-19-013
4
Department of Endocrinology, Brazil, 5 Department of Pathology, Immune reactivity to collagen V-150kD fragment: biomarker of in-
Brazil, 6 Department of Rheumatology, Brazil terstitial lung disease in systemic sclerosis
L. Brito1,2, A. Santos Filho3,2, J. Tomaz de Miranda1,2, V.L. Capelozzi1,4,
Background & Objectives: The immune reactivity to type V collagen W. Rosolia Teodoro1,2, A.P. Pereira Velosa3
1
(ColV) in patients with rheumatoid arthritis have suggested a role for Faculdade de Medicina, Universidade de Sao Paulo, Brazil,
2
autoimmunity to ColV as a major disease mechanism. The occurrence Rheumatology Division, Brazil, 3 Hospital das Clinicas HCFMUSP,
of in situ and humoral antibodies (AB) against collagen types during a Faculdade de Medicina, Universidade de Sao Paulo, Brazil,
4
histologically well-defined synovitis have been lacking. We evaluate the Department of Pathology, Brazil
synovial extracellular matrix and the autoantibodies in arthritis model.
Methods: Sprague-Dawley rats (n=9) were subcutaneously immunized Background & Objectives: Type V collagen (ColV) has antigenic prop-
with mBSA/PBS (500μg/200μl) in Freund's adjuvant. Arthritis was induced erties and the potential to become an autoantigen in interstitial lung dis-
on day 21, by intraarticular injection of mBSA/PBS (10μg/15μl) in the right eases, the most serious complication associated with Systemic sclerosis
knee. The animals were divided into three groups: 24 hours (AI-24h), 21 (SSc). Previously, we demonstrated that ColV-induced tolerance decreased
days (AI-21d) and 30 days (AI-30d) after induction of the arthritis. ELISA inflammation and pulmonary fibrosis in the SSc model. Our objective was
assays were employed to detect anti-collagen I-VAB in sera. Synovial tissue to evaluate the autoimmunity for ColV fragments in the model of SSc
was evaluated by H&E, immunohistochemistry and immunofluorescence. before and after tolerance induced by ColV for future diagnostic biomarker.
Results: Significant levels of circulating AB against collagen I, III and IV Methods: SSc model was induced in health rabbits (IM, n=12), by ColV
could not be detected in any group. The greatest elevation of AB directed immunization and in the 150 day six IM rabbits were submitted to ColV-
against type II collagen was found in AI-24h. Most strikingly, AB against induced nasal tolerance during 30 days (IM-TOL). All animals were
Virchows Arch

3
maintained until 210 days and sera samples were collected on 0, 150 and Strasbourg, Strasbourg, France, CHU de Strasbourg, Dèpartement de
210 days. The ColV was biochemically fractioned in aspartic acid-proline Pathologie, Strasbourg, France
linkages and enzymatically by pepsin and tripsin. The antibodies frequen-
cy to ColV-fractionated portions in sera of the SSc model was evaluated Background & Objectives: Cavitation of mesenteric lymph nodes is a
by immunoblotting and image analysis. rare complication of celiac disease of unclear pathogenesis, frequently
Results: The ColV biochemically fractionated resulted in about 6 frag- associated with hyposplenism. The diagnosis is usually made by radiol-
ments to aspartic acid-proline linkages; 6 and 5 fragments, respectively to ogists in a clinical setting of known celiac disease.
pepsin and tripsin enzymatic treatments. All 150 and 210 days sera sam- Methods: A 63 years-old male complained of chronic abdominal pain
ples reacted with the ColV fragments resulting of the enzymatic and and weight loss. Biologically, he showed thrombocytosis and anemia. A
biochemical treatments. However, only the 150kD-ColV fragment was PET/CT scan revealed non-hypermetabolic conglomerate of necrotic
immunologically identify with less intensity in IM-TOL compared to IM mesenteric lymph nodes, measuring 13 cm. Clinicaly, the differential
in the pepsin treatment (60.77±10.04 vs 288.7±155.9, p<0,001) and diagnosis included lymphoma, mycobacteriosis and Whipple disease.
aspartic acid-proline linkages (-80.72±5.979 vs 82.22±17.7, p<0,001). By laparoscopy, an excisional lymph node biopsy was performed.
Conclusion: Decreased reactivity to a 150kD-ColV fragment after ColV- Results: Histologically, central acidophilic lipid-containing, partly calci-
induced tolerance indicates that antigenic determinants important in au- fied necrosis, surrounded by dense fibrosis and non-atypical lymphoid
toimmunity to ColV in SSc model interstitial lung disease could be tissue was seen. No granulomatous reaction was observed. Ziehl and
inserted in these protein fractions. It suggests that this fragment may be Grocott stains, mycobacterial culture and PCR for Tropheryma Whipplei
a possible biomarker of immune reactivity in SSc interstitial lung disease. were negative. We proposed the diagnosis of mesenteric lymph node cav-
itation and recommended to explore a possible association with celiac
Supported by FAPESP (2016/05617-4; 2017/11865-3), LIM. disease. Small bowel biopsies were subsequently performed, showing atro-
phic villi with intra-epithelial lymphocytosis. A gluten-free diet was initi-
ated with remarkable improvement of gastrointestinal symptoms. An atro-
E-PS-19-014 phic spleen was detected after re-reviewing the abdominal imaging, which
Epidemiological and histopathological profile of metastatic might account for the patients’ thrombocytosis. Unfortunately, the patient
melanoma died few months later of myocardial infarction, confirmed by autopsy.
V. Nica1, C. Socoliuc1,2, R. Andrei1, C. Constantinescu1, C. Luca1, G. Conclusion: Cavitation of mesenteric lymph nodes is a rare complication
Tudor1, O. Stefan1, R. Tanasă1, G. Grigore1, S.A. Zurac1,2 of celiac disease, with fewer than 40 cases reported to date. Although
1
Colentina Clinical Hospital, Romania, 2 Carol Davila University of under recognized, its histological aspect is characteristic. Therefore, a
Medicine and Pharmacy, Romania correct identification becomes of paramount importance mainly when
imagistic findings are non-specific and celiac disease is unknown.
Background & Objectives: The main cause of death in melanoma is
widespread metastases. Metastases can develop in lymph nodes or in
distant organs. Our objective was to analyse metastatic melanoma from E-PS-19-016
epidemiological and histopathological standpoints. The importance of Major Histocompatibility Complex class I (MHC
Methods: We performed a retrospective study on all cases of metastatic I) and clinicopathological correlations in the diagnosis of Idiopathic
melanoma diagnosed in our pathology department between 2015 and Inflammatory Myopathies (IIM)
2019. Data collected included, age, sex, location and morphology. R.-Z. Bulf1, A. Vrancianu2, M. Dincă1, V. Mageriu3, E. Manole4, A.
Results: The study group comprised 88 patients with 14 cases without a Bastian2,5
1
known primary site based on available clinical information. The most fre- Clinical Hospital Colentina, Romania, 2 Pathology Department,
quent metastatic site was cutaneous (27 cases - 30,68%) followed by nodal Colentina University Clinical Hospital, Bucharest, Romania, 3 MedLife
(25), cerebral (22), pleuro-pulmonary (5), gastrointestinal (4), skeletal (3), Clinic, Bucharest, Romania, 4 Colentina Clinical Hospital; "Victor
ocular (1) and genitourinary (1) locations. Mean age at diagnosis was 60,07 Babes" National Institute of Pathology, Molecular Biology Laboratory,
in the group of cutaneous metastases, 59,08 in cases with lymph nodes Romania, 5 Carol Davila University of Medicine and Pharmacy, Romania
metastases and 55,5 years in the group of cerebral metastases. The morphol-
ogy of tumour proliferation was diverse, with various cell types encountered: Background & Objectives: The main purpose of this study is to evaluate
epithelioid, spindle, mixed epithelioid and spindle, clear cells, lymphoid and muscle biopsies in IIM - dermatomyositis (DM), polymyositis (PM),
rhabdoid cells. The epithelioid and mixed variants needed immunohisto- inclusion body myositis (IBM), autoimmune necrotizing myopathy
chemical confirmation in 47 (60,25%) cases and the more unusual variants (AINM) - taken from patients who received or not an anti-inflammatory
(spindle, clear cell, lymphoid and rhabdoid) in 7 (70%) cases. treatment before tissue prelevation.
Conclusion: Metastatic melanoma can have diverse anatomical locations and Methods: 141 patients (adult and juvenile cases) with clinical suspicion
various morphological aspects mimicking other malignancies (carcinoma, of IIM were divided in two groups: group I: 72 cases without prior steroid
lymphoma, sarcoma). Considering the significant number of cases without a therapy; group II: 69 cases with prior steroid therapy initiated due to
known primary in our study, in the absence of melanin pigment in tumour severe symptoms or non-responsiveness to therapy. Other cases with
cells, the diagnosis can be difficult, requiring immunohistochemical confirma- inflammation, but without IIM were microscopic polyangiitis, Pompe
tion. disease, trichinelosis. We performed histological stainings,
histoenzymology, histochemistry and immunohistochemistry (MHC I)
Work partially supported by a Romanian-Ministry-of-Research-and- on cryosections/paraffin embedded tissue; the fragment of skeletal muscle
Innovation grant no.61PCCDI⁄2018PN-III-P1-1.2-PCCDI-2017-0341. was obtained by open surgical biopsy.
Results: 43 cases had pathological confirmation of IIM: 32 in Group I -
17 cases DM, 11 cases PM, 2 cases AINM, 2 cases IBM; only 11 in
E-PS-19-015 Group II: 5 cases DM, 2 cases PM, 3 cases AINM, 1 case IBM. 40
Mesenteric lymph nodes cavitation as the presenting feature of coe- (56%) cases in Group I and 58 (84%) cases in Group II had non-
liac disease - the role of pathologist specific changes. MHC I was positive in all IIM cases in both groups.
A. Fattori1, N. Weingertner1, X. Argemi2, A. Nicolae1, M. Chenard3 Conclusion: Using MHC I marker is mandatory in diagnosing myositis
1
Department of Pathology, University of Strasbourg, Strasbourg, France, even in corticotreated patients, when morphological aspects are non-con-
2
Department of Infectious and Tropical Diseases, University of clusive. Corticotherapy increases the number of cases with non-specific
 Virchows Arch

diagnosis by up to 30%. It is strongly recommended to perform a biopsy heart (11.9%) and in brain vessels (9.5%). Air accumulations in the ves-
before initiating anti-inflammatory therapy and clinical and pathological sels were not detected in 66.7% of deceased newborns.
correlations are crucial. Conclusion: The presence of gas in the lungs, stomach and intestines in
the group of newborns indicates respiratory processes. Most often gas
detected in the heart cavities, heart and liver vessels at stillborn, and in
E-PS-19-017 the liver vessels at dead newborns.
Secondary malignancy: concept of development, etiopathogenetic
features, clinical and morphological comparison
D. Kushch1, M. Mnichovich1, M. Nikita1 E-PS-20-002
1
Research Institute of Human Morphology, Russia Childhood gastric carcinoma: a report of a case simulating
langheransian histiocytosis
Background & Objectives: A secondary malignansy is a new tumour A. Bdioui Thabet1, H. Busby2, N. Mhamdi2, A. Max2, C. Pierre2
1
that occurs several years after the treatment of the first cancer and has Georges Pompido Hospital Paris, France, 2 Brabois Hospital, Nancy, France
a structure and degree of malignancy different from the primary neo-
plasia. In connection with the increase in life expectancy in cancer Background & Objectives: Tumours of the stomach usually affect patients
patients, the number of patients with this pathology increases. The after the fifth decade of life. It has been estimated that patients younger than 40
main problem is the early removal of the patient from the register in years of age represent between 2% and 8% of all patients with gastric carcino-
oncological institutions, and, as a result, the decline in quality control ma. Symptoms are non-specific and deceiving, so diagnosis is usally belated.
of people at risk. Our objective is to report an extremely rare case of metastatic childhood
To study the etiology, the creation of a classification of secondary tumours. gastric carcinoma clinically simulating an histiocytosis.
Methods: Statistic - 85 cases of sectional observations and medical his- Methods: An 8-year-old boy, with no medical history, in particulary there
tories of patients with primary multiple and secondary tumours with de- was no familiar history of young age gastric carcinoma, admitted in paedi-
tailed histological, immunohistochemical studies of tumour material were atric departement for sous clavicular thrombosis. Radiologic examination
studied. shows many laterotarchial an cervical lymph nodes enlargment asociated
Results: A tumour is considered secondary if there is a fact of using with thoracic compression vertebra and lung interstitial syndroma; this
high doses of carcinogenic drugs in the treatment of primary cancer. clinical presentation suggested a langheransian histiocytosis.
It should also be more malignant compared with the first neoplasia. A cervical lymph node and a bone vertebra were biopsed and sent for
Secondary malignant tumours should be classified according to the type microscopic examination.
of therapy of the primary disease. 1. Secondary tumours resulting from Results: On histology, the lymph node was massivly infiltrated by large
chemotherapy. 2. Secondary tumours resulting from the use of hormone tumour cells with abondant cytoplasme and atypical repressed nuclei,
therapy. 3. Secondary tumours resulting from targeted therapy. 4. having the morphology of signet ring cells.The bone biopsy was also
Secondary tumours arising after radiation therapy. infiltrated by the same cells.
Conclusion: We need to create a specialized cancer registers, isolating On immunohistochemestry, histiocytic markers was negatives, although
secondary malignant tumours with a separate diagnosis, preventing their cytokeratin AE1/AE3 and cytokeratine 7 was strongly postive.
development, especially in risk groups, as well as choosing effective and Conclusion: Gastric carcinoma in children is extremely rare. However,
at the same time sparing methods of antitumor therapy to reduce its long- any persistent symptoms in children should be carefully examined. We
term effects, is becoming increasingly obvious. should consider and investigate the possibility of malignancy even in
young patients, and the diagnosis should be made at earlier stages, to
provide better chances for these patients to undergo curative treatment.
Sunday, 8 September 2019 – Wednesday, 11 September 2019
E-PS-20 | Paediatric and Perinatal Pathology
E-PS-20-003
Postmortem MRI and CT at autopsy of newborn with EPIGNATUS:
E-PS-20-001 a case report
Comparative post-mortem CT characteristics of air/gas accumula- U. Tumanova1, V. Lyapin1, V. Bychenko1, A. Kozlova1, A. Shchegolev1
tions in the bodies of stillborn and dead newborns 1
NMRCOGP, Russia
U. Tumanova1, V. Lyapin1, V. Bychenko1, A. Shchegolev1, G. Sukhikh1
1
NMRCOGP, Russia Background & Objectives: Objective: to evaluate the effectiveness of
postmortem MRI and CT for the newborn with epignatus.
Background & Objectives: The use of postmortem CT allows for an We present the case of a newborn girl, born at gestational age of 30 weeks
objective non-invasive assessment of the localization of gases, which helps and died in the first minutes after birth. Tumour-like formations from the
to clarify the severity of postmortem changes and links of tanatogenesis. mouth and nose were on external examination. CT and 3TMRI were
To study the features of localization of gas accumulations in organs and performed 8 hours after death before the autopsy. The analysis of tomo-
tissues of stillborn and dead newborns by postmortem CT. grams and 3D-reconstructions were performed. Virtopsy data were com-
Methods: 18 bodies of stillborn at 25-39 gestation weeks (Group-I) and pared with the autopsy results.
42 deceased newborns (Group-II) were studied. CT scan was performed Methods: When complex Virtopsy, a teratoma of the soft tissues of the face -
after 4-15 hours from the death before the autopsy. Localization of gas epignatus (volume 200 cm³) was revealed. It originated from the nasal cavity
accumulations in vessels and body cavities was determined on tomo- (os ethmoidale) spreading to the oral cavity and to the front of the neck.
grams. The flotation tests were performed during autopsy. In Group-I Obstruction of the upper respiratory tract, deformation and underdevelopment
gas was detected in 50% of observations, in Group-II - in 90.5%. of the upper jaw bones and face soft tissues, displacement of the organs of the
Results: In Group-I, gas was visualized in the heart cavities, heart and neck by tumour, gas in the vessels of the neck were detected.
liver vessels (38.9%), in brain vessels (33.3%), in abdominal vessels Results: At postmortem MRI and CT, the structure of the formation
(27.8%), in aorta (22.2%). revealed a soft tissue component with the fat inclusions and bone frag-
In Group-II, air accumulations were observed in the lungs (59.5%), in the ments, multiple cysts with liquid up to 5 cm in diameter.
intestines (57.1%), in the stomach (38.1%), in the liver vessels (19.0%), At microscopic examination was a picture of mature teratoma with the
in the abdominal vessels (16.7%), in the heart cavities (16.7%), in the presence of elements of dense and loose fibrous connective tissue,
Virchows Arch

adipose and muscle tissue, salivary glands, cartilage, neuroglia, choroid and hydrops fetalis. Up to 70% of type 2 CPAM has related
plexuses, cysts lined with multi-row, ciliated or intestinal epithelium. malformations. Here we demonstrate two cases of CPAM.
Conclusion: Postmortem CT and MRI allowed to identify the growth Methods: Retrospective case analysis.
source and structural features of the tumour at our research case. Results: Case 1: A 32-week-old female neonate died of respiratory in-
Virtopsy increases the efficiency of pathological study, which demon- sufficiency 37min after birth. At 30 week-appointment CPAM of right
strates the feasibility of postmortem CT and MRI in the cases of congen- lung was diagnosed, followed by intrauterine left pleuro-amniotic
ital malformations. shunting. During autopsy facial and genital dysmorphias, anal atresia
and generalised edema is noticed, as well as pleural and peritoneal effu-
sions. Right lung is enlarged (36g), multicystic, compressing on medias-
E-PS-20-004 tinum and left lung (6g). Case 2: A 23-week-old female fetus after an
Placental myofibroblastic units remodeling in pregnancies of women elective pregnancy termination due to prenatally diagnosed, rapidly pro-
with congenital heart disease gressive CPAM, involving whole right lung, therefore expected to lead to
L. Rudiuk1,2, O. Reshetnikova1 perinatal death. External examination does not reveal any dysmorphic
1
Immanuel Kant Baltic Federal University, Kaliningrad, Russia, features. Internally in situ organ localisation with enlarged right lung
2
Regional Clinical Hospital of the Kaliningrad region, Kaliningrad, and shifting mediastinum, compressing on heart and left lung.
Russia Microscopically lung masses from both, fetus and neonate, were similar:
dilated bronchiole-like cystic spaces dispersed among gestation propriate
Background & Objectives: A pregnancy with congenital heart disease lung tissue, lined by columnar, ciliated epithelium, surrounded by
(CHD) carries a high-risk of complications during pregnancy and deliv- fibromuscular layer, without mucin-producing cells, cartilage structures,
ery both for mother and a fetus. Surgical interventions are not curative; consistent with type 2 CPAM.
therefore pregnant women with CHD may face hemodynamic impair- Conclusion: CPAM is rare cause for neonatal death, therefore early di-
ments. A range of pregnancy complications for the mother and baby are agnosis, purposeful screening for associated malformations and dynamic
rooted in placental dysfunction. The favorable outcome of pregnancy and evaluation is crucial, as it can affect perinatal outcome and help in con-
delivery is provided when placental function is adequate to fetal-maternal sulting and decision-making process for parents.
system demands. The aim of present study is the research of
myofibroblastic units remodeling of placental villous chorion in cases
when pregnancy is complicated with CHD. E-PS-20-008
Methods: 35 term placentas, including 20 cases of CHD and 15 cases of Wilms tumour arising in a metanephric adenoma of kidney
physiological pregnancy (controls) were studied morphologically. P. Khneisser1, S. Asmandar1, R. Ramirez1, P. Cervera2, s. boudjemaa1, R.
Histological slides, stained with hematoxylin and eosin, were studied Braum3, C. Pasqualini4, E. Colomba5, A. Verschuur6, A. Coulomb7
1
microscopically, then they were analysed by point count method and Sorbonne Universitè- APHP6, Hôpital Armand Trousseau, Service
using the computer morphometry. Histopathologic findings were corre- d'Anatomie et Cytologie Pathologiques, Paris, France., France, 2 APHP
lated with medical history data and immunohistochemical studies. The Sorbonne Universitè, France, 3 Centre mèdico-chirurgical Ambroise
immunohistochemical staining protocol with monoclonal mouse antibod- Parè/Pierre Cherest, Clinique Hartmann, Paris, France, 4 Dèpartement
ies to SMA (Dako, 1:500), Collagen IV (Neomarkers, 1:25) for placental de Cancèrologie de l'Enfant et de l'Adolescent Gustave Roussy,
tissue samples had been developed. Differences between groups' data Villejuif, France, 5 Institut Gustave-Roussy, service d'oncologie,
were elucidated by non-parametric Mann-Whitney. Reliability Villejuif, France, 6 Paediatric oncology and haematology department,
established at p<0.05. La Timone Hospital, Marseille, France, 7 Sorbonne University, APHP6,
Results: The research showed the increased volume fraction (VF) of the Pathology department, Armand Trousseau Hospital, Paris, France
terminal villi both in central and peripheral areas of placental disk in cases
of CHD. Intervillous spaces were smaller mainly due to fibrinoid accu- Background & Objectives: Wilms tumour (WT), the most common pae-
mulations. SMA expressions were higher and diffuse than in controls. VF diatric renal malignant tumour, may occur in adults. Metanephric adenoma
of a cell surface with SMA positive reaction revealed in 14.0(5) % in the (MA), a benign epithelial tumour of the kidney, occurs predominantly in
central area and 24,0(5)% in peripheral zone of placentas with CHD adults and children. Because of morphological similarities between these
(respectively -11,0(5)% and 20,5(9,25)%, р<0,05 in controls). two entities, MA may represent maturing WT or nephrogenic rests.
VF of a cell surface with Collagen IV positive reaction also was higher in Coexistence of two or more renal tumours is extremely rare as described in
CHD group with more intense reaction at placental periphery than in a case reports. MA may notably be associated with WT and renal cell
central areas (26,0(9)% and 19,0(6)% compared with18,5(7)% and carcinoma.
11,5(7,75)% , р<0,05 in controls). Methods: We reviewed clinical, pathological and genetic data of these
Conclusion: Placental myofibroblastic units remodeling considered in renal tumours to establish the links between WT and MA.
the aspect of placental adaptation to circulatory hypoxia due to hemody- Results: A 39-year-old man presented a 19 cm kidney tumour diagnosed
namic impairments in women with CHD. as WT on biopsy. The patient was treated by preoperative chemotherapy
according to localized WT International Society of paediatric Oncology
(SIOP) protocols followed by right total nephrectomy. The nephrectomy
E-PS-20-007 specimen showed a multinodular, solid/cystic, 20 X 9 X 8.5cm tumour
Congenital pulmonary airway malformation type 2: a rare cause of developed on the convexity of the kidney. Microscopically,
perinatal death Chemotherapy induced changes (CIC) were evaluated at 40% and viable
M. Riekstina1,2, I. Franckevica1,2, R.M. Verdijk3, I. Strumfa2,4 tumour showed immature epithelial component (60%) with stromal
1
Children's Clinical University Hospital, Latvia, 2 Riga Stradins (39%) and blastemal (1%) components. At the periphery of the tumour,
University, Latvia, 3 Erasmus MC University Medical Center a rim of benign looking epithelial cells suggestive of an underlying MA
Rotterdam, The Netherlands, 4 Department of Pathology, Latvia was present. A diagnosis of WT arising in MA was made and confirmed
by BRAF expression on immunohistochemistry and BRAF (V600E) mu-
Background & Objectives: Congenital pulmonary airway malformation tation using NGS in the MA component.
(CPAM) is lower respiratory tract developmental abnormality comprising Conclusion: WT may develop in a MA in adult. Despite morphological
up to 25% of all congenital lung lesions, with favourable perinatal sur- similarities, these two entities have different pathogenesis and molecular
vival. Poor outcome mostly is associated with large, progressive lesions alterations, notably BRAF mutation in MA.
 Virchows Arch

E-PS-20-009 E-PS-20-011
Diagnostic challenges in hydatidiform mole How to find a pin in a haystack? An autopsy case of rare genetic
R. Balan1, I.D. Caruntu1, S. Giusca1, L. Lozneanu1, T.A. Balan1, A. mutation causing immunodeficiency
Grigoras1, C. Amalinei1 K. Ristmägi1
1 1
"Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania East-Tallinn Central Hospital, Estonia

Background & Objectives: Hydatidiform moles (HMs) are subdivided Background & Objectives: Life was like a box of chocolates. You
into complete and partial, according to genetic, morphologic, and clini- never know what you're gonna get. You can easily adjust this
copathologic differences. Although typical forms are diagnosed on rou- saying to pathology. You can have a new finding just by doing
tine histopathology, the ultrasound diagnostic of pregnancy reveals incip- your everyday work.
ient morphological features of HM, difficult to recognize and differenti- Methods: In Estonia guidelines for pregnancy monitoring and delivery
ate. We aimed to assess the histopathology of complete and partial HM, exist for decades. Still sometimes infant does not survive and then it`s
creating a diagnostic algorithm, based on routine and immunohistochem- obligatory to perform an autopsy. In 2017 the infant mortality rate was 2,3
ical examination. per 1000 livebirths. This number has been quite stable.
Methods: Our retrospective study included 48 gestational products repre- Results: A case presentation is about a boy who was born from the
sented by 34 partial moles and 14 complete moles. The routinely stained normal pregnancy at term. The family had one sibling before. The
slides were histopathologicaly reevaluated and the expressions of p57 and child become ill on the second week of life, was admitted to the
Ki-67 were immunohistochemical assessed on archival tissues. hospital with the symptoms of acute respiratory disease. On a reg-
Results: Partial moles presented scalloped enlarged edematous and small ular examination nothing significant was found. After a week of
fibrotic villi, with less central cisterns, and mild trophoblastic hyperplasia. supportive treatment he was dismissed at home. The second epi-
Complete moles showed round enlarged edematous villi, with central cis- sode of similar illness was two weeks later. The child had a fever,
terns, circumferential trophoblastic proliferation, with cytologic atypia. p57 respiratory distress and signs of shock. With the progressive wors-
expression was diffuse in the villous stroma and the cytotrophoblast of partial ening of a status he died 2 days later. The autopsy and gene
moles and absent or low in the intermediate trophoblast of the complete analyses were requested. At autopsy the signs of acute shock were
moles. Ki-67 presented a stronger immunoexpression in complete moles. found, on histological slides the unusual picture of pulmonary can-
Conclusion: The most important aspect of histopathological diagnosis of didiasis was presented and the results of gene test – a rare muta-
HM is to distinguish complete from partial moles, due to the higher risk of tion – concluded and explained the course of this odd case.
the former to develop persistent gestational trophoblastic disease. When Conclusion: The case presentation illustrates the good collaboration be-
microscopical features are very subtle, the immunohistochemical evalu- tween different institutions. Autopsy like a method of investigation loses
ation of p57 and Ki-67 can be helpful, as complete mole does not express it’s significance day by day, but what about the role of pathologist?
p57 but has a high Ki-67 index. However, because HMs share distinct
molecular genetic features, the difficult cases can be assessed by genotyp-
ing the products of conception. E-PS-20-012
Pathological factors in nephroblastoma: a study of 100 cases in
Tunisian children
E-PS-20-010 N. Boujelbene1, I. Abbes1, R. Doghri1, L. Charfi1, R. Ben Ghorbel1, D.
Double Meckel's diverticulum described in a foetus with trisomy 18 Kacem1, K. Mrad1, M. Driss1
T. Domsa1, T. Kovacs2,3, D. Crisan1, F. Stamatian2, A. Staicu3, C. Albu2,1 1
Department of Pathology, Salah Azaiez Institute, Tunisia
1
Iuliu Hatieganu University of Medicine and Pharmacy, Department of
Pathology, Cluj-Napoca, Romania, 2 IMOGEN- Centre of Advanced Background & Objectives:
Research Studies, Cluj-Napoca, Romania, 3 Iuliu Hatieganu University Nephroblastoma is the most frequent malignant renal tumour in children.
of Medicine and Pharmacy, 1st Department of Obstetrics and Microscopic examination evaluate the tumour stage often after chemo-
Gynaecology, Cluj-Napoca, Romania therapy. We aimed to assess histopathological factors in a series of chil-
dren treated for nephroblastoma.
Background & Objectives: Meckel’s diverticulum is the most common Methods: We retrospectively analysed the data of consecutive children
congenital anomaly of the digestive tract, resulting from the incomplete diagnosed in our hospital between 2001 and 2017 as having
obliteration of the omphalomesenteric duct. The presence of a double nephroblastoma. All tumours were identified and categorized according
Meckel’s diverticulum is a very rare finding. We describe such a case, to the International Society of Paediatric Oncology (SIOP) 2001. Staging
discovered at the post-mortem examination of a fetus with trisomy 18. system and the histology risk grouping were also determined according to
Methods: A 22 weeks of gestation fetus, resulted from a spontaneous preg- SIOP 2001.
nancy, was diagnosed at routine ultrasound with a polymalformative syn- Results: A total of 100 cases of nephroblastoma diagnosed in 48 boys
drome. Following quantitative flourescent PCR that revealed trisomy 18, after and 52 girls were included. The median age was 38 months (range
proper counseling, the patient opted for therapeutic termination of pregnancy. from 2 to 156 months). Bilateral tumour was observed in 7 cases.
Upon arrival in the pathology service, the fetus was analysed by conventional Surgery was performed after chemotherapy in 95 of 100
autopsy. The internal organs were immersed in 10% formalin and subsequent- patients.Ninety-one patients (91%) presented with localized disease,
ly a microscopic examination was performed. whereas 9 patients had metastases at diagnosis (lung only). Wilms
Results: Postmortem examination revealed a 500g female fetus with low- tumours were unilateral in 93 children and bilateral in 7
set, malformed ears, bilateral undeveloped thumbs and radial agenesis. At children.Histopathologically, 79% were classified as “intermediate-
internal examination, ventriculomegaly, right-sided bronchial isomerism risk” tumours, 17% were classified as “high-risk” tumours and 4% as
and double Meckel’s diverticulum were identified. The rest of the organs “low-risk” tumours.The final local stage (ie, the stage on which post-
were developed according to gestational age. At the microscopic exami- operative treatment was based) was stage I in 39.5%, stage II in 25%,
nation, two true diverticuli were confirmed, layered by small intestinal- stage III in 19%, stage IV in 9.5% and stage V in 7%. All patients
type mucosa. At the tip, one of them also contained heterotopic colonic who had ruptures were staged pathologically as stage III.
mucosa. Conclusion: It is important to perform a standardised macroscopic and
Conclusion: We present, to our knowledge, the first case of double microscopic examination in the management of nephroblastoma (SIOP
Meckel’s diverticulum described in a fetus. 2001 protocol) for optimal therapeutic management.
Virchows Arch

Results: Only few of the Physicians (22.87%) were aware of the concept
Sunday, 8 September 2019 – Wednesday, 11 September 2019
of Critical Alerts in surgical pathology whereas only 26.9% of them
E-PS-21 | Pathology in Favour of Developing Countries
agreed that they receive notification of Critical values in surgical pathol-
ogy reports. Respondents (62.4%) were mainly concerned regarding de-
layed turnaround time of the reports having critical alerts. Majority of
E-PS-21-001
physicians (93.5%) were of view that Information (Date, time, responsi-
Ensuring cancer patient safety in gross room; analysis of 175 near-
ble individual and person notified) must be documented during critical
miss events and errors in tumour specimens at a university affiliated
alerts notification on the report.
hospital in Lahore, Pakistan
Conclusion: In developing countries like Pakistan, there’s dire need to
F. Rehman1, S. Mahmood1, S. Hameed1, N. Khalil1, S. Ahmed1, M.Z.
improve the approach of the pathologists towards identifying, reporting
Sarwar1
1 and timely communicating the critical alerts so that physicians can initiate
King Edward Medical University, Lahore, Pakistan
rapid & effective management of the patient.
Background & Objectives: All the tumour specimens submitted at
pathology receptions are subjected to gross examination in the
E-PS-21-003
gross room. Negligence at any step during gross examination
Use of electronic & social media in the education and training of
may result in misinterpretation of the lesion thus significantly af-
pathology resident; an experience from Lahore, Pakistan
fecting patient treatment & prognosis. Aim was to document errors
F. Rehman1, S. Mahmood2, A. Hassan3, H.T. Khan3, S. Ahmad3, M.Z.
generated in handling of surgical specimens from patients with
Sarwar3, A. Momina4
malignancies. 1
King Edward Medical University, Lahore, Pakistan, 2 King Edward
Methods: A total of 175 tumour specimens including biopsies and Medical University, Lahore, Pakistan, 3 King Edward Medical
resection specimens were included in the study. Following parame- University, Lahore, Pakistan, 4 King Edward Medical University,
ters were assessed during gross examination. Pre-analytical errors Lahore, Pakistan
like; crushed, fragmented biopsies not receiving all components of
specimen, putting specimen from different sites in same jar, margins Background & Objectives: Social media is defined as a web or mobile-
unlabeled, mislabeled specimen, autolysed specimen, inappropriate based technology that helps in the production and colloquy of user-
fixative, inappropriate lymph nodes sampling/location whereas some generated content. There are various means of training and education in
of the analytical errors include inappropriate recording of specimen the field of medicine such as worldwide web, YouTube, Facebook,
dimensions, insufficient tumour sampling, inadequate decalcification WhatsApp, Twitter, Messenger etc.
and margin selection. The aim of this study is to determine the role of electronic and social
Results: Most of the errors observed during pre-analytical phase signif- media in the education and training of pathology residents working in
icantly affected the interpretation of gross examination findings. Errors different medical institutions of Lahore, Pakistan.
during analytical phase mainly resulted from negligence, inappropriate Methods: A cross sectional descriptive survey was conducted involv-
training, and supervision of the designated staff handling the gross ing 125 postgraduate residents working in four sub-specialties of the
specimens. pathology including haematology, histopathology, chemical patholo-
Conclusion: Standard operating procedures for grossing the tumour gy and microbiology. The respondents were evaluated by means of a
specimens must be followed in true spirit. Individuals involved in the self-designed questionnaire prepared after extensive literature search.
specimen grossing have to be fully trained and vigilant in performing It covered various aspects of demographic profiles of pathology res-
their assigned task so as to avoid potential harm to the cancer patient idents and their awareness and patterns of using different social net-
as a result of any mischievous act and negligence during grossing of working sites relevant to the field of pathology. Data was entered and
tumour specimen. analysed using SPSS version 21.
Results: All postgraduate residents filled the questionnaire with a
100% response rate. Most of the respondents (78.81%) had access
E-PS-21-002 to internet with 100 % of them having mobile-based technology for
Critical alerts in surgical pathology; physician's perception, practice using social networking sites. Most frequently used social network-
and expectations from pathologist ing site was WhatsApp (83.05%), followed by Facebook (62.71%),
F. Rehman1, S. Mahmood1, K. Naz1, S. Ahmed1, M.Z. Sarwar1 YouTube (44.91%), messenger (33.05%) and twitter (30.50%).
1
King Edward Medical University, Lahore, Pakistan Awareness & patterns of use of social media by pathology residents
is depicted in table 1 and figure 1 & 2.
Background & Objectives: To avoid any delay in the management of Conclusion: Since the evolution of 21st century electronic media,
patient, critical alerts have to be identified and notified timely to the use of social networking sites has significantly affected our lives
physicians. However, in developing countries, the concept of and attitudes. It has also opened new horizons in the field of pa-
Critical Alerts is not yet fully addressed. The main purpose of this thology education by providing a platform for sharing of pathology
study was to analyse the current practices in identifying and lectures, posting of routine & problematic cases in pathology, live
reporting critical alerts, to evaluate perception of physicians and to streaming of slide seminars and participation in various discussion
apprehend their expectations regarding Critical Alerts in histopa- forums.
thology department of King Edward Medical University/Mayo
Hospital, Lahore.
Methods: A total of 188 physicians participated in the study with a E-PS-21-004
100% response rate. Participants were selected by non-probability, Female genital tuberculosis clinically masquerading as a neoplastic
convenient sampling. A questionnaire covering different aspects of process
perceptions, practices and expectations of physicians regarding crit- B. Simona1, A.C. Lisievici2, T.A. Georgescu3, F. Pop4
1
ical alerts in surgical pathology was distributed among practicing Spitalul Universitar de Urgenta Bucuresti (SUUB), Romania, 2 Carol
physicians from affiliated hospitals of King Edward Medical Davila University of Medicine and Pharmacy, Bucharest, Romania,
3
University, Lahore. Ethical approval was taken from institutional Department of Pathology, Bucharest Emergency University Hospital,
review board. Romania, 4 "Dr. Carol Davila" University Hospital of Nephrology, Romania
 Virchows Arch

Background & Objectives: Genital tuberculosis is a rare form of E-PS-22-002

secondary tuberculosis, comprising approximately 9% of all extra- Cytogenetic damage in buccal epithelium in lung cancer patients
pulmonary forms. Patients with Mycobacterium Tuberculosis infec- M. Byakhova1, K. Anoshkin2, V. Byakhova3
1
tion affecting the female genital tract usually present with infertility, M.F. Vladimirskiy Moscow Region Research Clinical Institute,
dyspareunia and chronic inflammatory pelvic disease, but, rarely, Moscow, Russia, 2 Research Center for medical genetics, Moscow,
they can also have tumour-like symptoms. Russia, 3 Peoples' Friendship University of Russia (RUDN University),
Methods: We report the case of a 66-year-old female from a rural Moscow, Russia
region in Romania, with no history of pulmonary tuberculosis, who
presented to our clinic with weight loss, abnormal vaginal discharge Background & Objectives: Genomic damage is probably the most
and pelvic pain. Computerized tomography revealed thickened endo- important fundamental cause of developmental and degenerative on-
metrium and a diffuse parenchymal process in the uterine corpus, cological diseases. It is essential to have reliable and relevant min-
extending bilaterally to the fallopian tubes and ovaries, with ascites imally invasive biomarkers to improve the implementation of bio-
buildup. Findings were suggestive for serous carcinoma. After mul- monitoring, diagnostics, and treatment of diseases caused by, or
tidisciplinary evaluation, the patient underwent total hysterectomy associated with, genetic damage. The micronucleus (MN) assay in
with bilateral oophorectomy and peritoneal washing. buccal cells is potentially can be such a biomarker. The aim of our
Results: Histopathological examination of the surgically resected study was to determine the cytogenetic status of buccal epithelium in
specimen revealed massive tissue destruction with disseminated patients with lung cancer (LC).
caseous granulomas, composed of lymphocytes, epithelioid cells Methods: This study was based on a group of patients (38 patients),
and giant multinucleated Langhans cells involving the uterus, median age 63,7 years old, with the diagnosis of LC. The control group
endocervix and fallopian tube. Ziehl-Neelsen staining revealed included 30 apparently healthy people, who didn’t have either acute or
red acid fast bacilli, consistent with the diagnosis of tuberculosis. chronic diseases at the time of this study.
No neoplastic process was identified. Clinical management in- Results: There was a trend for a significant increase (p <0.01) of
volved major ethical issues, because the patient refused treatment, cells with cytogenetic abnormalities in patients with LC in buccal
but after developing pleurisy, she eventually accepted bacteriostatic epithelium: cells with micronuclei (1,76 (1,01÷2,5)‰) was 2,8
treatment. times higher than healthy ones (0,6 (0,19÷1,05)‰). The ratio of
Conclusion: Although rather frequent in Romania and other developing cells with protrusions (1,5 (1,0÷2,0)‰) is 2 times higher than
countries, genital tuberculosis may not have specific symptoms and may healthy ones (0,75÷1,49)‰). Total indicators of the share of cells
even mimic a neoplastic process. It is associated with increased morbidity with micronuclei and protrusions (3,2 (2,2÷4,3‰) are 2,5 times
and adequate treatment should be rapidly administered, in order to pre- higher compared with the same indicators in healthy ones (1,3
vent an otherwise curable disease from having an unfortunate course of (0,3÷2,37)‰).
evolution. Conclusion: Thus, the increase in cytogenetic damage in the cells of
buccal epithelium indicates the systemic nature of the changes in LC
cancer.
Sunday, 8 September 2019 – Wednesday, 11 September 2019
E-PS-22 | Pulmonary Pathology
E-PS-22-003
A rare case of lung adenofibroma
E-PS-22-001 N. Balint1, M. Charton-Bain1, P. Riera1
Broncho-pulmonary cancers, about a series of 180 cases 1
Centre Hospitalier du Pays d'Aix, France
Z. Merad1
1
CHU Sidi Bel Abbes, Algeria Background & Objectives: Lung adenofibroma is not a defined
entity in books but rare numbers of cases have been described in
Background & Objectives: Brocho-pulmonary cancer is the most the literature.
common cancer in the world. It is the leading cause of cancer It was first described by Scarff and Gowar in 1944 whom implied that its
mortality. The prognosis is bleak with a 5-years survival estimated origin might be identical to lung cartilaginous hamartoma. We present a
at less than 10% due to late diagnosis. The objective of the work case of pulmonary adenofibroma located in the inferior lobe of the left
is to carry out a descriptive epidemiological and histopathological lung in a 71-year old patient with a history of hemangiopericytoma. The
study to highlight the extent of morbidity of bronchopulmonary lesion was discovered by scanner examination because of a persistent
cancers cough.
Methods: This is a series study of 180 cases of primary Methods: Macroscopically the lesion measured 2.2 x 2.4 cm and had a
bronchopulmonary cancers collected in the Department of Anatomy lobulated appearance, being well delimited by surrounding tissue with a
and Cytology Pathologies at the Sidi Bel Abbes Hospital University from white homogenous surface, a firm consistency. The microscopical exam-
January 1996 until December 2014 ination showed a biphasic tumour with an epithelial glandular component
Results: Diagnosis was made on biopsies in 117 cases, pleural fluid forming ramified spaces surrounded by a spindle-cell lax stroma. The
in 61 cases and surgical specimens in 02 cases There is a clear glandular spaces were compressed and coated by a cuboidal or flattened
male predominance, 73% for the male and 27% for the female The epithelium without atypia. An immunohistochemical panel containing
distribution by age shows a peak frequency between 68-77 years CK7, CD34 and Ki67 was used.
with extremes ranging from 24 years to 82 years. Results: The histological aspect, combined with the immunohisto-
Histopathologically non-small cell lung cancer (98%) predominates chemical panel which showed positivity for CK7 in the epithelial
largely in small cell lung cancer (02%). Squamous cell carcinomas component, focally for CD34 on the stromal component and the
(79%) and adenocarcinomas (17%) are the most frequent. Ki67 index of about 2%, led us to the conclusion that this was
Conclusion: This study gives an overview of the distribution of indeed an adenofibroma.
lung cancers in the Department of Pathology at the Sidi Bel The diagnostic is easily made because of the fibroepithelial aspect
Abbés Hospital-University, which declares late, hence the impor- which resembles a breast fibroadenoma, but it imposes a differen-
tance of developing a screening program and appropriate manage- tial diagnosis with other benign tumours of the lung: hamartomas
ment for those with advanced cancer. or solitary fibrous tumour.
Virchows Arch

Conclusion: It is important to note that such lesions are benign entities, easily E-PS-22-006
recognizable by their histological appearance with an extremely rare Correlation predominant type of adenocarcinoma of the lung with
localisation in the lung for which the surgical excision is the curative gesture. characteristics of primary tumour
M. Miladinovic1, M. Golubović1, L. Vučković1, F. Vukmirović1, T. Lakic2,3
1
Medical Faculty, University of Montenegro, Clinical center of
E-PS-22-004 Monetenego, Montenegro, 2 University of Novi Sad, Faculty of
Anaplastic lymphoma kinase (ALK) expression in lung adenocarci- Medicine, Serbia, 3 Clinical Center of Vojvodina, Novi Sad, Center for
noma - clinicopathologic and morphologic features Pathology and Histology, Serbia
D. Jasar1, K. Kubelka-Sabit1, V. Filipovski1,2
1
Clinical Hospital Acibadem Sistina, Department of Histopathology and Background & Objectives: In 2015, the World Health Organization
Cytology, Republic of North Macedonia, 2 Medical Faculty, University (WHO) adopted a new classification of adenocarcinoma of the lungs
Goce Delchev, Republic of North Macedonia (AD), which almost completely accepted the recommendations of the
International Association for the Study of Lung Cancer, American
Background & Objectives: The aim of this study is to explore the status Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS)
of ALK in lung adenocarcinomas and to evaluate the relationship be- 2011. The prognostic importance of the new classification of AD is still
tween ALK expression and clinicopathological and morphological fea- not clear. We analysed the correlation of predominant histologic subtypes
tures of the primary tumour. of AD with the characteristics of the primary tumour (size, infiltration of
Methods: In total, 86 cytological and biopsy specimens were tested for pleura and surrounding structures).
ALK status using automated immunostainer with Ventana anti-ALK Methods: 148 operatived patients with invasive AD were analysed. We
(D5F3) antibody. The expression of ALK was correlated with patient’s defined the predominant type using the IASLC / ATC / ERS criteria
age, sex and histological features of the primary tumour. (solid, acinar, papillary, micropapillary and lepidic). We compared the
Results: ALK positive expression was detected in 15 (17,4%) cases, in correlation of prevalent types with tumour characteristics.
significantly younger age group than ALK negative patients (p<0.05). Results: The most prevalent types of AD were solid (35.1%), acinar
Mucinous type of lung adenocarcinomas were predominantly ALK pos- (31.1%) and papillary (16.9%). The smallest average tumour size was
itive (43,7%), followed by papillary type (25%), acinic type (13%) and found in papillary (39.6 mm), solid (49.9 mm), acinar (47.8 mm),
solid type (3%). There was strong correlation between the ALK expres- while the highest was in the lepidic (52,4 mm) and micropapillary
sion in surgical biopsy and cytological specimens (p<0.05). (55.8 mm). The most prevalent type with pleural infiltration was
Conclusion: These results represent that immunohistochemical expres- solid (6.8%), acinar (6.1%) micropapillary (6.1%), with statistically
sion of ALK gene rearrangement is valid detection technique revealing significant association (Fisher's non-parametric test, p = 0.011).
distinctive clinicopathological and morphological features of the tumour Infiltration of surrounding structures was found in acinar (2%) and
especially in scant biopsies and cytological specimens. solid (2%).
Conclusion: In this paper, we point the importance of an accurate assess-
ment of the subtype of AD highlighting certain aspects of its clinical
E-PS-22-005 relevance and potential impact on future new research in this direction.
Genetic analysis of multiple synchronous lung cancer in a single lobe
showing three different histological types
S. Aida1, M. Kato1, N. Sakaniwa2, T. Okunaka2 E-PS-22-007
1
Department of Pathology, Mita Hospital, International University of A case report of exon 20 resistant insertion
Health and Welfare, Japan, 2 Department of Respiratory Surgery, Sanno S. Boukansa1, S. El Bardai2, Z. Benbrahim3, N. Mellas3, H. El Fatemi4,5
1
Hospital, Japan Medical Centre of Biomedical and Translational Research, Faculty
of Medicine and Pharmacy Fez, Morocco, 2 Anatomy and Cyto-
Background & Objectives: We experienced a case of multiple synchro- pathologycal department, CHU HASSAN II Fez, University Sidi
nous lung cancer in a single lobe showing three different histological Mohamed Ben Abdellah, Morocco, 3 Department of Oncology,
types. The results of genetic analysis of the tumours showed interesting CHU HASSAN II Fez, University Sidi Mohamed Ben Abdellah,
findings to suggest a developmental mechanism of collision cancer. Morocco, 4 Department of Pathology, Hassan II University
Methods: Case presentation: A 73-year-old Japanese woman with a his- Hospital, Fez, Morocco, 5 Faculty of Medecine and Pharmacy of
tory of smoking for 20 years (50 cigarettes daily). She had undergone a Fez, Morocco
partial colectomy due to colon cancer 7years before. The follow up CT
revealed tumour shadows in S6 and S10 of the right lower lobe of lung. Background & Objectives: Most patients whose tumours harbor ex-
Partial lung resection of right S6 and S10 was performed on the suspicion on19 deletions or L858R mutations have substantial clinical and
of colon cancer metastasis. The resected tumours were histopathological- radiographic responses to EGFR TKIs. In contrast to the classic
ly, immunohistochemically and genetically examined. activating EGFR mutations, insertions in exon 20 are not often
Results: S6; A 10mm sized solid adenocarcinoma was seen. The tumour associated with clinical benefit and radiographic responses with
cells were immunohistochemically positive for TTF1. P53 mutation Ex6 EGFR TKIs, they have been linked to insentivity and resistance to
S215G was detected, S10: Two distinct adjacent tumours were seen. One reversible and irreversible EGFR TKIs. These include the exon 20
was 20mm sized large cell neuroendocrine carcinoma which was i n s e r t i o n m u t a n t s D 7 7 0 ( i n s G ) N 7 7 1 T, D 7 7 0 i n s ( S V Q ) ,
immunohistochemically positive for TTF1, synaptophysin and CD56. D770_N771(inS NPG) that account for about 4% of all EGFR
P53 mutation Ex7 P250L was detected. Another was 12mm sized lepidic mutations.
adenocarcinoma, immunohistochemically positive for TTF1. P53 muta- Methods: We report a case of 36 year-old-male, occasional smoker for 5
tion Ex7 P250L was detected. The two tumours were connected each years, presented with a two month history of bone pain. Chest radiograph
other in a small area. revealed a large opacity overlying the right upper lobe. Magnetic reso-
Conclusion: The two tumours in S10 are morphologically consistent nance imaging (MRI) showed lung, bone and liver metastases. A bron-
with collision cancer but the genetic analysis of p53 mutation suggests chial biopsie was performed for pathological diagnosis, which revealed
that they are derived from a common multipotential cell. The tumour in an acinair adenocarcinoma with intensively positive TTF-1 and CK7 in
S6 has different p53 mutation from S10 tumours and is proved to be not a differentiated glandular structure. For genetic testing, the extraction of
metastasis but a primary cancer. DNA was performed with invitrogen DNA FFPE Tissue Kit from
 Virchows Arch

obtained histological sample. EGFR mutations was detrminated by PCR Methods: A 26-year-old female patient complained for fever for the last
amplification followed by automatic direct sequencing. two weeks, persistent after antibiotics administration. Chest X-ray
Results: Molecular analysis revealed an EGFR exon 20 insertion showed an area of consolidation occupying the right lower lobe of the
(D770_N771insG), wich associated with resistance to targeted EGFR lung, while computed tomography (CT) suggested lung abscess. A tho-
TKIs and correlated with a poor patient prognosis. As treatment, the racotomy was followed. Α lung tissue specimen measured 11x1,5x1,3cm
patient received radiotherapy with 20 cycles, followed by 6 cycles with was sent for intraoperative consultation.
palliative chemotherapy. 5 month later, the patient had progressive dis- Results: Frozen sections showed fibrosis, necrosis and suppuration.
ease. Then, a new strategy of treatement will be discussed with At the periphery of the specimen there were scarce large cells. For
oncologists. permanent sections, a lung specimen measured 7X6X4cm was sent.
Conclusion: A few studies have focused on exon 20 insertion, wich Paraffin sections from both specimens revealed central area of ne-
D770_N771insG is a rare mutation, that may reflect the fact that the crosis and suppuration, at the periphery of which, a lymphogranulo-
clinical and pathological characteristics associated with this subset are matous tissue containing a few Hodgkin and Reed-Sternberg cells was
not well established. The present report highlits the clinicopathological identified. Immunohistochemically, these neoplastic cells were positive to
characteristics of a young patient with exon 20 resistant insertion. CD30 and CD15 antibodies and negative to CD45. Thus, the diagnosis of
classical HL was made.
Conclusion: When HL infiltrates lung without mediastinal involve-
E-PS-22-008 ment or hilar lymphadenopathy, the term primary pulmonary HL
Unusual case report: intimal sarcoma of pulmonary artery for a (PPHL) is used. PPHL may present necrosis and suppuration imi-
young male tating clinically and radiologically lung abscess. Although PPHL is
A. Ruminaite1, L. Poskiene1, V. Sarauskas1 rare, it should be included in the differential diagnosis of lung ab-
1
Member of Lithuanian Society of Pathologists, Lithuania scess and a high index of suspicion from pathologists is recom-
mended for the accurate diagnosis.
Background & Objectives: To present extraordinary uncommon case-
based scientific research of intimal sarcoma of pulmonary artery (PAS) in
a 33-year-old male patient. PAS are very rare tumour with only a few E-PS-22-010
hundred cases reported. The incidence is estimated between 0.001 and Immunohistochemical profile of small-cell neuroendocrine carcino-
0.003% but is likely underestimated because of frequent misdiagnosed as ma of lung: review of 110 cases
pulmonary embolism and may remain unrecognized if not examined M.I. Oviedo Ramírez1, G. Ruiz García2, A. Salazar Nicolás2, L. Barona
histologically. García2, M.I. Ortuño Moreno2, M. Capelini3, J.O. López Ojeda4, A.
Methods: In 2018, a 33-year-old male presented with a complaint of Caballero Illanes2, E. Gómez Plata5, E. Martínez Barba2
1
fatigue, progressive dyspnoea and fever that last for a few months. Heart Servicio de Anatomía Patológica, Hospital Clínico Universitario Virgen
magnetic resonance imaging and computed tomography revealed tumour de la Arrixaca, Spain, 2 Servicio de Anatomía Patológica, Hospital
in a proximal segment of pulmonary artery with secondary thrombosis and Clínico Universitario Virgen de la Arrixaca, Spain, 3 Urgencias atencion
ischemic changes in a right lung. A biopsy of pulmonary artery mass was primaria Cartagena, Spain, 4 Hospital General Universitario los Arcos del
performed confirming a diagnosis of high grade mezenchymal tumour Mar Menor, Spain, 5 Centro Oncológico Estatal ISSEMYM, Spain
with more evidence for intimal sarcoma. Tumour cells were positive for
vimentin, CD31, around 30% of cells were positive for smooth muscle Background & Objectives: Small-cell neuroendocrine carcinoma of
actin and F VIII factor. Ki67 proliferation index reached nearly 70%. lung is one of the most frequent types within endobronchial biop-
Results: Later on, pathologists received surgical specimen of the right sies. Although it shows characteristic histopathological finding, im-
lung and segment of pulmonary artery with tumour masses. Additional munohistochemistry is necessary in many cases due to the variety of
immunohistochemistry reactions were done. The final diagnosis – pul- possible differential diagnoses. The expression of the different
monary artery intimal sarcoma, G3, with pulmonary artery obstruction markers usually employed as CKAE-1AE3, TTF-1 and neuroendo-
and infiltration into the lung tissue. One day after the surgery patient died. crine markers varies according to the literature. In particular, it is
Conclusion: PAS most commonly occur in right or left pulmonary artery very important to know that these neoplasms can show negative
or pulmonary valve. These malignancies primarily metastasize to lung immunostain for epithelial markers and even for TTF-1.
and mediastinum (50%). Currently, there is no recognized staging and Methods: The archive were reviewed between the years 2009-2014,
specific grading system. Overall prognosis is dismal with median survival obtaining 110 cases. There were 97 mens and 13 women.The median
below 18 months. age was 72 ( range betwen 41 to 90 year old). We studied 78 biopsies
and we also included 32 cases of lung FNA.
Results: From 110 cases we found 7.27% that were negative for
E-PS-22-009 TTF1 immunostain and 1.8% with negative immunostain for
A case of primary pulmonary Hodgkin lymphoma presenting as lung CKAE1-AE3. The rest of neuroendocrine markers were
abcsess chromogranin, synaptophysin and CD56, which were negative in
K. Zarampouka1, E. Margariti2, K. Tziomalos2, S. Tsagkaropoulos3, C. 11.92%, 22% and 2.75% respectively with varying degrees of
Foroulis3, T. Koletsa1 immunostaining.The immunochemistry of TTF-1 was intense and
1
Pathology Department, Medical School, Aristotle University of difusse in 34 cases. Two cases showed TTF-1 immunostain mul-
Thessaloniki, Thessaloniki, Greece, 2 First Propedeutic Department of tifocal and the rest of cases were of low intensity. We exclude 33
Internal Medicine, Medical School, Aristotle University of cases in which the immunostaining was not performed.
Thessaloniki, AHEPA Hospital, Thessaloniki, Greece, 3 Department of Conclusion: There are few bibliographical references to the per-
Cardiothoracic Surgery, Medical School, Aristotle University of centage of negativity for TTF1 and CKAE1-AE3 in this tumour.
Thessaloniki, AHEPA Hospital, Thessaloniki, Greece The negativity for CKAE1-AE3 and TTF-1 is considered extreme-
ly rare. This study contributes important information, since it
Background & Objectives: Primary Hodgkin lymphoma (HL) of the characterises immunoprofile of small-cell carcinoma. This infor-
lung is very rare. We present a case of primary pulmonary HL with mation is useful in cases that show a usual morphology of small
clinical and radiological presentation of abscess in order to raise aware- cell neuroendocrine carcinoma but with unusual immunohisto-
ness of this lymphoma manifestation. chemical expression.
Virchows Arch

E-PS-22-011 architecture. These were covered by cuboidal or columnar respiratory epithe-

Intraoperative frozen sections of an undiagnosed pulmonary artery lium, as well as mucinous epithelium, with well-differentiated goblet cells,
intimal sarcoma. A case report forming scattered groups or tufts. The cysts were separated by fibrous septa,
M. Kilmpasani1, A. Baliaka1, A. Madesis2, E. Serasli3, T. Karaiskos2, G. with only rare presence of cartilaginous tissue. These formations were min-
Drossos2, S. Papaemmanouil1 gled with dilated alveoli, filled with numerous foamy macrophages and
1
Department of Pathology, General Hospital of Thessaloniki "G. mucin.
Papanikolaou", Greece, 2 Department of Cardiothoracic Surgery, In correlation with the radiologic findings and the patient’s history, the
General Hospital of Thessaloniki "G. Papanikolaou", Greece, diagnosis was congenital pulmonary airway malformation, type 1.
3
Pulmonary Department, General Hospital of Thessaloniki "G. Conclusion: The incidence of CPAM is approximately 1 case per 10,000-
Papanikolaou", Greece 35,000 pregnancies, and is constantly increasing, due to the improvement
of prenatal ultrasound diagnostics. About 80% of the cases are diagnosed
Background & Objectives: Intimal sarcoma is an extremely rare, in the first 2 years of age. Its clinical manifestation varies from asymp-
aggressive malignant neoplasm. A few hundred cases are de- tomatic to as severe as perinatal death. CPAM is rarely diagnosed in
scribed in the literature, mostly located in the pulmonary artery, adulthood, and the most common symptom is cough. It is associated with
and often diagnosed postmortem. We present the case of a 69- a risk of recurrent pulmonary infections, as well as malignant transforma-
year-old woman, admitted with symptoms of massive pulmonary tion. Therefore, resection and histological examination of the affected
embolism. tissue is advised, even in the asymptomatic cases.
Methods: Intraoperatively, material from the right pulmonary artery
was obtained and examined in frozen sections. Subsequently, a right
pneumonectomy was undertaken. We observed a mass protruding in E-PS-22-013
the lumen of the pulmonary artery and filling its branches in a mold- Calcified pachypleuritis, a major sign of exposure to asbestos: elim-
like manner. We performed hematoxylin-eosin and immunohisto- inate a malignant mesothelioma first!
chemical stains. F. Chadi1, N. Bourhroum2, N. Mahassini2
1
Results: The frozen sections demonstrated a malignant neoplasm Pathology Department of Mohamed V Military Teaching Hospital,
with sarcomatous features. It consisted of highly pleomorphic Rabat, Morocco, 2 Pathology Department of Ibn Sina Universitary
cells with evident mitotic activity, in an oedematous or slightly Hospital, Rabat, Morocco
myxoid background. The cells were either spindle-shaped with
enlarged, elongated nuclei, or round to oval-shaped with vesicular Background & Objectives: If cancers are the main concern of the health
nuclei. There were also scattered multi-nucleated cells with lobu- consequences of exposure to asbestos, it is the non-malignant diseases,
lar nuclei. largely dominated by pleural plaques, which are by far the most frequent
The interpretation of the frozen sections as sarcoma was con- affections due to exposures to this mineral.
firmed in the paraffin sections. Moreover, the tumour seemed to Methods: We report the case of a 70-year-old woman who worked at the
originate from the intima of the pulmonary artery. The neoplastic Moorish bath for 45 years, admitted for the management of acute chest
cells stained positive for smooth muscle actin and negative for pain with acute coronary syndrome.
CD34 and desmin. The diagnosis of a pulmonary artery intimal The discovery of basal-thoracic pleural thickening with a syndrome of
sarcoma was given. fluid effusion having motivated the realization of a CT scan which
Conclusion: The true incidence of pulmonary artery intimal sarcoma is showed the presence of a non-parenchymal calcified pleural plaque.
unknown, because it is most often misdiagnosed. The initial symptoms of Results: After inconclusive pleural biopsies, a parietectomy decision
pulmonary embolism, as well as the radiologically demonstrated with pathological examination in favour of a calcified pachypleuritis
intravasal growth of the tumour, may be misleading, regarding the imme- without sign of malignancy.
diate need for surgical therapy. In these cases, histologic examination is Conclusion: This observation also confirms the diagnostic difficulties
the most reliable tool for the correct diagnosis. raised by minor pleural or pulmonary images, frequently identified during
routine CT screening, and the need for precise diagnostic criteria, given
the compensatory consequences attached to them.
E-PS-22-012
A case of congenital pulmonary airway malformation in adulthood,
presenting as hemoptysis E-PS-22-014
M. Kilmpasani1, N. Pastelli1, A. Baliaka1, I. Dimitriadis1, T. Karaiskos2, Emperipolesis-type giant cell carcinoma of the lung: relevance of PDL1
K. Bismpa3, S. Papaemmanouil2 A. Handra-Luca1, I. Onorati1, P. Guiraudet1
1 1
Department of Pathology, General Hospital of Thessaloniki "G. APHP University Paris Nord, France
Papanikolaou", Greece, 2 Department of Cardiothoracic Surgery,
General Hospital of Thessaloniki "G. Papanikolaou", Greece, 3 CT and Background & Objectives: The emperipolesis-type (null-type) of lung
MR Department, General Hospital of Thessaloniki "G. Papanikolaou", giant cell carcinoma (GCC) was recently identified as specific tumour
Greece group (Weissferdt and Moran 2016) as different from the syncytial-type.
We aimed to report the morphological and immunohistochemical features
Background & Objectives: Congenital pulmonary airway malformation of a series of 7 cases of emperipolesis-type GCC of the lung.
(CPAM), previously known as congenital cystic adenomatoid malforma- Methods: The 7 tumours, detected on surgical resection specimens, were
tion (CCAM), is a rare lung parenchyma hamartomatous lesion, diag- analysed for morphological and immunohistochemical features.
nosed mainly in the prenatal period, infancy or early childhood. We pres- Results: The gender ratio was 1:6 (female:male), the age ranged 41-79 years.
ent the case of a 38-year-old man, admitted with hemoptysis, due to a Excessive smoking was known in 5/7 cases, neoadjuvant chemotherapy in
hitherto undiagnosed CPAM. 1/7, radiochemotherapy in 1/7 (12 years previously for breast cancer). The
Methods: A segmentectomy of the upper lobe of the right lung was tumour size ranged 1.5-6.5 cm. All tumours showed necrosis, mild in 3. All 7
performed. The material was examined with hematoxylin-eosin and im- tumours were TTF1-positive and contained adenocarcinoma-type zones (mu-
munohistochemical stains. cus-secreting, 4). Squamous cell differentiation (CK5/6 and/or p63 positivity)
Results: The lung tissue demonstrated multiple, variably sized cystic forma- was detected in 4 tumours. PDL1 was expressed in 6/6 tested tumours. PDL1
tions, measuring 0.2-3.5cm in diameter, causing effacement of the lung expression by giant tumour cells was heterogenous within a same tumour.
 Virchows Arch

Emperopoletic PDL1-positive tumour cells contained PDL1-positive or fashion /Verocay bodies (Type A areas) intermingled with hypocellular areas
PDL1-negative emperipolesied tumour or inflammatory cells. There was no with abundant edema (Type B areas). Some cells exhibited atypia and
relationship to PD1-positive inflammatory cells. hyperchromatic nuclei. Mitotic activity was low (Ki67<5%). Calcification
Conclusion: Emperipolesis-type GCC of the lung may show TTF1 ex- and infiltration by lymphomononuclear cells and histiocytes as well as
pression and may occur in association to adenocarcinoma or squamous hyalinized vessels were observed. Our diagnosis was pleural ancient
cell differentiation. PDL1 expression in emperipoletic tumour cells sug- schwannoma.
gest a possible interference with the acquisition of phagocytic capacities, Conclusion: Ancient schwannoma of the pleura is a rare entity. Patients
being known that macrophages also express PDL1. become symptomatic when tumours attain large size. Complete surgical
excision is curative with excellent prognosis. Malignant transformation is
rare. It is important to keep this rare tumour in mind for the differential
E-PS-22-015 diagnosis of intrathoracic lesions.
Diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH) ac-
companied by a pulmonary adenocarcinoma: case report
K. Revelos1, Z. Almpanis1, K. Siafakas2, M.T. Revelou1, C. Spiliadi3 E-PS-22-019
1
Pathology Department, 251 Hellenic Air Force General Hospital, Pulmonary Langerhans Cell Histiocytosis (PLCH)
Greece, 2 Thoracic Surgery Department, 251 Hellenic Air Force I. Vamvakaris1, E. Psychogiou1, D. Riga1, A. Mandilara1, P. Megas1, A.
General Hospital, Greece, 3 Pathology Department, Athens Medical Papadopoulou1
1
Center, Greece General Hospital of Thoracic Diseases of Athens "Sotiria", Greece

Background & Objectives: DIPNECH is an exceedingly rare disorder Background & Objectives: Langerhans cell histiocytosis (LCH) is a
which is being recognized with increasing frequency. It is usually pre- pathological entity characterised by proliferation of Langerhans cells. It
sented in combination with carcinoid tumorlets, obliterative bronchiolitis can present either as a localized or as a systematic disease. PLCH is
and fibrotic lung diseases. Reports of DIPNECH in association with an uncommon and presents either as a diffuse process or as a solitary nodule.
adenocarcinoma are extremely limited in the literature. The majority of patients are current or former smokers, aging approxi-
Methods: A 78 - year old female patient referred to our hospital because mately 40 years, with no significant sex predilection. In 38-57% of cases
computed tomography and PET-CT scans revealed a tumour-like lesion V600E/BRAF mutations are found.
measuring 3,5 cm, in its widest dimension, in the upper lobe of the left Methods: A 38-year-old female patient, current smoker, presented to our
lung. The patient had a long history of chronic obstructive complaints hospital with chest pain and dyspnea. Chest X-ray revealed interstitial-
such as cough, shortness of breath and wheezing and was under treatment like lung lesions in the lingular parenchyma. After thorough clinical/
for chronic obstructive pulmonary disease (COPD). She had no smoking laboratory examination, the patient underwent open lung biopsy.
history. In previous CT scans, over a 10 year’s period, the lesion of the Results: The specimen from the lingula included a solitary nodule 0,4 cm in
upper left lobe and small nodular lesions in both lungs were identified, but greater diameter, white-tan, solid and elastic in consistency. Microscopically
there were considered as fibrotic processes. The main lesion became we observed interstitial infiltration by many eosinophils, variable numbers o
larger in size and with a central compact component. mononuclear inflammatory cells and numerous large sized cells with mor-
Results: A left upper lobectomy was performed and a well differentiated phological and immunohistochemical (CD1a+, S-100+) features consistent
adenocarcinoma of mixed subtype, with lepidic and papillary pattern, was with Langerhans cells. The neighbouring parenchyma was characterised by
diagnosed. Within the tumour but also in distant sites of the lobe BOOP-like lesions. We concluded to the diagnosis of PLCH.
DIPNECH foci were identified in association with terminal airways and Conclusion: The localized and solitary form of PLCH is a rare entity
measured less than 5mm in greatest diameter. The diagnosis was con- affecting young smokers. It may be totally asymptomatic or present with
firmed by immunohistochemistry. acute pulmonary and/or systemic symptoms and may be a clinical
Conclusion: DIPNECH in association with an adenocarcinoma is a rare mimicker of malignancy. Its correlation with V600E mutations of
condition and a causal relationship was previously suggested. Increased BRAF oncogene plays significant role in targeted therapies.
awareness for the diagnosis and better understanding of the disorder and
its associated pathologies is needed.
E-PS-22-020
Primary Pulmonary Malignant Melanoma (PPMM)
E-PS-22-018 I. Vamvakaris1, D. Riga1, E. Psychogiou1, G. Chamalakis1, P. Megas1, A.
Ancient schwannoma of the pleura Mandilara1, A. Papadopoulou1
I. Vamvakaris1, E. Psychogiou1, D. Riga1, P. Megas1, A. Papadopoulou1, 1
General Hospital of Thoracic Diseases of Athens "Sotiria", Greece
A. Tsonou1
1
General Hospital of Thoracic Diseases of Athens "Sotiria", Greece Background & Objectives: Malignant melanoma (MM) is one of the
most aggressive and treatment-resistant skin cancers. Primary pulmonary
Background & Objectives: Schwannomas are rare benign tumours orig- malignant melanoma (PPMM) is extremely rare, accounting and with a
inating from Schwann cells. Ancient schwannoma is a variant of rather poor prognosis. To assure the diagnosis, extrapumonary origin
schwannoma which presents as an encapsulated tumour usually located must be ruled out by thorough evaluation.
retroperitoneally. Ancient pleural schwannomas are rare, with less than Methods: A 56-year-old male patient was referred to our hospital
twenty cases reported in the literature. with progressive dyspnoea and cough. Medical history included
Methods: We report the case of a 57-year-old female who presented with high arterial pressure and smoking. Physical examination was nor-
sudden onset breathlessness and cough. HRCT revealed an enhancing mal. Chest X-ray and HRTC revealed an enhancing mass in the
mass in the right thoracic cavity. The patient underwent thoracotomy left upper lobe extending to the splachnic pleura. Thoracotomy
and excision of a well circumscribed encapsulated pleural mass measur- revealed a black-pigmented mass measuring 4 cm in greatest di-
ing 5,8 x 5,1 x 4,8 cm. ameter and wedge biopsy was performed.
Results: The specimen we received was tan-white to yellow, with cystic Results: The specimen we received included a lobular black-pigmented
change and haemorrhage. Microscopy revealed a hypercellular mesenchymal lesion, solid in consistency, infiltrating the resected pleura.
neoplasm consisting of spindle/elongated cells (S-100+), cytologically bland Microscopically, the tumour displayed histological and immunohisto-
with wavy nuclei, granular chromatin, arranged in a palisading or organoid chemical features compatible with MM (HMB45+, S100+). Mesothelial
Virchows Arch

and epithelial markers were negative (Calretinin, BerEp4, KLMW). We of the University of Coimbra, Coimbra, Portugal, 4 CIMAGO - Research
asked the clinicians for a detailed search of possible sites of primary MM Center for Environment, Genetics and Oncobiology, Faculty of Medicine,
(skin, mucous membranes, scalp, palms, plants, eyes, nasopharyngeal/ University of Coimbra, Coimbra, Portugal, 5 Centre of Pulmonology,
oral mucosa, genitals) which was negative. We concluded to the diagnosis Faculty of Medicine of the University of Coimbra, Portugal, 6 Institute
of PPMM. The patient underwent 12 months chemotherapy and immu- of Anatomical and Molecular Pathology, Faculty of Medicine, University
notherapy and is still on strict follow-up program. of Coimbra, Portugal, 7 CIMAGO - Research Center for Environment,
Conclusion: Although extremely rare, PPMM should be considered in Genetics and Oncobiology, Faculty of Medicine, University of Coimbra,
the differential diagnosis of primary pulmonary tumours. It can masquer- Portugal
ade as histologic types of tumours such that the pathologist must “think
melanoma”. During the investigation of a suspected PPMM, one must Background & Objectives: Combined small cell lung carcinoma (C-
always bear in mind that MM of the skin may spontaneously regress SCLC), correspond to 5%–28%, most commonly associated with adeno-
despite having metastasized, posing a diagnostic challenge. carcinoma (ADC) and with squamous cell carcinoma (SCC); EGFR mu-
tations occur in less than 5% of pure SCLC, reaching 15%–20% in C-
SCLC.
E-PS-22-021 Methods: Four cases of C-SCLC were selected, where two were com-
Combined SCLC recognised by immunohistochemistry will not ex- bined with ADC (one male and one female, between 70-73y), and the
clude patients from molecular treatment other two cases, combined with SCC (males, aged between 72-77y);
R. Almeida1,2, A. Alarcão3,4,5, A.F. Ladeirinha3,4, M.R. Silva6,7, T. staged from IA2 to IVA (AJCC). Global survival was between 4-
Ferreira3,4, A.I. Rodrigues3, V. Sousa3, L. Carvalho3 61months, being between 6-8months in C-SCLC/ADC, and 4-
1
Centro Hospitalar e Universitário de Coimbra - Pathology department, 61months in C-SCLC/SSC.
Portugal, All cases were submitted to Ion AmpliSeqTM Colon and Lung Cancer
2
Faculty of Medicine in Coimbra, Portugal, Research Panel v2. (22 genes), after manual independent microdissection.
3
Institute of Anatomical and Molecular Pathology, Faculty of Medicine
Results:

Histopathology Immunohistochemistry NGS

Case 1 SCLC CK7+, TTF1+, CD56+, Ki67 100% PIK3CA: .1633G>A;p(Glu545Lys)

BRAF: c.1397G>A;p(Gly466Glu)
TP53: c.586C>T;p(Arg196Ter)
TP53: c.305C>T;p(Thr102Ile)
STK11: c.109C>T;p(Gln37Ter)
ADC CK7+, TTF1+, CD56-, Ki67 50% Non amplified
Case 2 SCLC CK7+, TTF1+, CD56+, Ki67 100% EGFR: c.2582T>A;p.(Leu861Gln)
TP53: c.376T>G;p(Tyr126Asp)
ADC CK7+, TTF1+, CD56-, Ki67 40% EGFR: c.2582T>A;p.(Leu861Gln)
TP53: c.376T>G;p(Tyr126Asp)
Case 3 SCLC CD56+, Chromogranin+, CK5.6+, Ki67 100% TP53: c.814G>A;p(Val272Met)
SCC CD56-, Chromogranin-, CK5.6+, Ki67 50% Non amplified
Case 4 SCLC CK5.6-, Chromogranin-, CD56+, Ki67 95% Wild-type
SCC CD56-, Chromogranin-CK5.6+, Ki67 40% Wild-type

Conclusion: p53 pathway persisted as the common mutation, rais- Background & Objectives: Endobronchial fibroepithelial polyp is a rare
ing similar progression as verified in germinative tumours. In this and benign tumour first described by Patterson in 1930. Benign tracheo-
series we cannot follow any particular molecular trace, while the bronchial tumours account for 1.9 % of all pulmonary tumours and there
applied immunohistochemical panel showed homogenous expres- are only about 30 case reports of airway fibroepithelial polyps in the
sion in both patterns of the combined tumours, allowing the di- scientific literature. The average age at diagnosis is 61 years and men
agnosis in biopsies. Treatment demanding molecular studies will are most frequently affected. These lesions feature an increased risk of
gather further knowledge to not exclude patients. complications, including life threatening conditions.
Methods: We report the case of a 65-year-old male presenting with dry
cough, right latero-thoracic pain and recurrent pneumonia. The patient
E-PS-22-022 underwent bronchoscopy which revealed a mobile branching polypoid
Bronchial fibroepithelial polyp - case report of a histologically benign lesion, partially obstructing the right lower lobe bronchus. A biopsy was
lesion with potentially severe clinical implications performed and histopathological examination revealed a polypoid fibro-
B. Simona1, A.C. Lisievici2, T.A. Georgescu3, F. Pop4 vascular stroma with lymphocytic infiltrate, covered by normal respirato-
1
Spitalul Universitar de Urgenta Bucuresti (SUUB), Romania, 2 Carol ry epithelium. The findings were suggestive for an endobronchial
Davila University of Medicine and Pharmacy, Bucharest, Romania, fibroepithelial polyp and the patient underwent lower lobectomy due to
3
Department of Pathology, Bucharest Emergency University Hospital, consolidation and recurrent episodes of pneumonia.
Romania, 4 "Dr. Carol Davila" University Hospital of Nephrology, Results: Upon gross examination, the specimen revealed diffuse fibrosis
Romania and changes of chronic congestion. The right lower lobe bronchus
 Virchows Arch

3
presented a 1.3/1.1/1.0 cm endobronchial polypoid mass with lobulating Medical Oncology Service, La Paz University Hospital, Madrid,
contour, glistering surface and no signs of bronchial wall invasion. Spain, 4 Cancer Epigenetics Laboratory, INGEMM, La Paz University
Histopathological examination revealed multiple papillary projections Hospital, Madrid, Spain, 5 Biomarkers and Experimental Therapeutics in
branching from a central fibrovascular core, covered on multiple sides Cancer, IdiPAZ, Madrid, Spain, 6 Hospital Universitario La Paz, Spain
by columnar pseudostratified cells with cilia and focal squamous meta-
plasia. Although a straight-forward histological diagnosis, bronchial Background & Objectives: PD-L1 nowadays is the most important
fibroepithelial polyp may sometimes raise clinical suspicion of malignity. biomarker in order to select patients with NSCLC who will receive im-
Conclusion: Airway fibroepithelial polyps are uncommon benign lesions munotherapy. We have studied the relation between PD-L1 expression,
of unknown etiology that are usually diagnosed due to symptopms related clinic-histologic factors and survival.
to the bronchial obstruction, such as recurrent pulmonary infections or Methods: PD-L1 was analysed in 130 lung surgical specimens from our
atelectasia. Clinically, they can sometimes mimic a malignant neoplasm, department between 2017 and 2018 by immunohistochemistry with 22C3
but the characteristic lobulated contour might be helpful in the differential Dako Clon and EnVision Flex visualization system in immunostaining
diagnosis of various other endobronchial neoplasms. autostainer Link 48. We collected histologic and clinical factors (histo-
logic subtype and grade, lymphovascular invasion (LVI), perineural in-
vasion, stage, age, sex and smoking status). Grading Adenocarcinoma
E-PS-22-023 (AD) is obtained by the addition of the percentages of the subtypes with
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. A same grade and choosing the highest result. Survival analysis has been
case report and review of literature studied using IBM SPSS statistics 22 program and a descriptive analysis
A. Sanz Zorrilla1, M.T. Gonzalez Serrano2, F. Granados Pacheco3, A. was carried out, followed by a survival analysis using the Kaplan-Meier
Martínez Lopez2, H. Fuentes Vaamonde1 estimator. To correlate PD-L1 expression and the histological and clinical
1
Hospital Universitario Reina Sofía, Córdoba, Spain, 2 Pathology factors, we performed Kruskal-Wallis, Wilcoxon and Spearman tests.
Department Hospital Universitario Reina Sofía, Córdoba, Spain, Results: We retrieved 46 women and 84 men cases. The average age is 68
3
Agencia sanitaria Hospital Costa del Sol, Marbella, Spain years old. 41 were smokers, 68 ex-smokers, 19 non-smokers and 2 un-
known. 92 were AD, 35 squamous cell carcinoma (SCC), 2
Background & Objectives: Diffuse idiopathic pulmonary neuroendo- Adenosquamous carcinoma and 1 NDCLC. PD-L1 expression related
crine cell hyperplasia (DIPNECH) is a rare idiopathic disease with only with histologic subtype SCC (p=0,003), grade 3 (P= 0,0001), LVI
about 100 cases reported in the literature to date. WHO Classification 2015 (p=0,003), solid (p=0,028) AD pattern (p= 0,046) and no driver mutations
has considered it as a precancerous lesion of a lung neuroendocrine tumour. (p= 0,01). The median overall survival (OS) was greater in patients with-
It is characterised by diffuse clustered, linear or nodular neuroendocrine cell out mediastinal lymph node involvement than in patients with mediastinal
hyperplasia without basement membrane breakthrough within bronchial lymph node involvement (p=0.006, HR= 0,2 95% ic (0,05-0,71)).
mucosal epithelium. If localized infiltrative growth and nodule formation Conclusion: Our results are consistent with the literature, although we haven´
are shown with basement membrane breakthrough, nodule diameter ≤5 mm t found reported LVI and as a histologic factor related with PD-L1 expression,
is called a carcinoid tumourlet and nodule diameter >5 mm is called a so this is our main contribution. In survival study we haven´t found statisti-
carcinoid. Here we report a case of this infrequent disease. cally significant differences in most factors probably because of the short
Methods: A 67-years-old woman presented had no smoking history. The follow-up. We propose to enlarge the follow-up and further studies.
patient had ERGE and long evolution cough syndrome. A routine chest
radiography and chest Computed Tomography (CT) revealed multiple
small nodules scattered in all pulmonary areas. A double pulmonary E-PS-22-025
wedge resection was performed. Pulmonary adenocarcinoma with micropapillary component metas-
Results: Histologically, the pulmonary architecture was preserved, and tasizing to the breast
there was a proliferation of pulmonary neuroendocrine cells within and Z. Mijovic1, D. Mihailovic1
1
around bronchiole. Also, there was partially broke through bronchial wall Institute of Pathology, Medical Faculty, University of Nis, Serbia
and displayed nodular infiltrative growth; nodules were all <5 mm in
diameter; cell size and morphology were relatively consistent; chromatin Background & Objectives: Although lung cancer is the most common
was fine granule-like. Immunohistochemical staining of the cells all cancer worldwide, the incidence of pulmonary carcinoma, particularly
showed AE1/AE3 (+), synaptophysin (Syn) (+), chromogranin A with micropapillary component, metastasizing to the breast is very rare.
(CgA) (+), and Ki-67 hyperplasia index 2%. We present a case of breast metastasis from pulmonary adenocarcinoma,
Conclusion: DIPNECH is a rare and preinvasive disease that could be which was initially interpreted as a primary breast cancer.
difficult to diagnose. The minimum criteria needed for this diagnosis are Methods: A 67-year-old female patient presented with dyspnea and chest
the presence of several group PNE cells in small airways combined with pain. On chest radiograph pleural effusion was found. After physical
carcinoid tumourlets. It should be included in the differential diagnosis of examination poorly defined mass was noted in the upper outer quadrant
micronodular formations, especially in middle-aged women without his- of the right breast. The patient underwent excisional breast biopsy and
tory of smoking. The accurate diagnosis of DIPNECH allows for the thoracoscopy.
implementation of appropriate treatment and channels further manage- Results: On histological analysis the breast biopsy specimen demonstrat-
ment of the patient into the right direction. ed multiple foci of adenocarcinoma with micropapillary component,
desmoplastic reaction and lymphovascular invasion, which was morpho-
logically similar to that seen in the pleural biopsy. The surrounding breast
E-PS-22-024 parenchyma demonstrated fibrocystic dysplasia without evidence of in
PD-L1 expression study in 130 non-small cell lung cancer (NSCLC) situ carcinoma. The immunohistochemical staining markers for breast
surgical specimens and correlation with clinic, histology and survival including estrogen receptor (ER), progesterone receptor (PR),
S. Hernandez Bonilla1, L. Blasco Santana2, L. Gutierrez Sainz3, C. mammaglobin and gross cystic disease fluid protein-15 (GCDF-15) were
Rodriguez-Antolin4, R. Rosas5, P. Cruz Castellanos3, E. Ruiz-Bravo6, I. negative. Lung cancer markers of thyroid transcription factor-1 (TTF-1)
Esteban Rodriguez1,5 and Napsin A were strongly positive which further supported the diagno-
1
Pathology department, La Paz University Hospital, Madrid, Spain, sis of primary lung adenocarcinoma with micropapillary pattern with
2
Pathology Department, La Paz University Hospital, Madrid, Spain, metastasis to the breast and pleura.
Virchows Arch

Conclusion: The distinction between metastasis from lung adenocarci- included areas of necrosis, microcalcification, granulomatous inflamma-
noma, particularly with micropapillary pattern which is recently recog- tion with macrophages, incl. multiple giant cells, lymphocytes and plasma
nized as an important prognostic factor, and primary breast adenocarci- cells. A large number of cysts contained mucus admixed with inflamma-
noma may cause a significant diagnostic dilemma. The contribution of tory debris and macrophages. In two cases cysts werelined with cylindri-
immunohistochemistry to the correct diagnosis is very important. cal to cuboidal epithelium and in one case the lining epithelium was
focally attenuated and flattened. Perivascular areas showed various de-
grees of lymphocytic infiltration. Bronchial walls demonstrated chaotic
E-PS-22-026 distribution of smooth muscle fibers. The transverse sections of bronchi
Morphological and microscopic features of the oral cavity in patients were lined with ciliated pseudocolumnar epithelium with goblet cells. In
with pulmonary tuberculosis blood vessels, smooth muscle cell proliferation was found.
B. Aitbay1 Conclusion: Use of computerized diagnostic imaging techniques is
1
Karaganda Medical University, Kazakhstan required to prove anomalous systemic arterial supply of the seques-
trated lobe which is essential to the diagnosis. The microscopic
Background & Objectives: Today tuberculosis (TB) referred as one of changes per se are non-specific and manifest with hypoplasia/
the widespread diseases. Kazakhstan is among the countrieswith the cyctic lesions and inflammatory reactions of variable type and in-
highest burden of the tuberculosis in terms number of TB cases during tensity, which sometimes hide the underlying disease.
the year. However, for the last 10 years the morbidity rate of the tubercu-
losis in Kazahkstan reduced in 2.4 times (from 125.5 in 2008 till 52.2 in
2017 for 100 thousand people). Despite the numerous studies and greatest E-PS-22-029
achievements, the relationship of the disease and dentistry is not Pleural epithelioid malignant mesothelioma with psammoma bodies
completely explored. Aim of the study is investigate the changes in the in a young female: a diagnostic challenge
hard tissue of the teeth and oral fluid of patients with pulmonary tuber- î Ilyès1, O. Iurcsuk1, K. Straub1, B. Nagy1, T. Kálmán1, A. Burszán-
culosis for the detection of Mycobacterium tuberculosis. Barabás2, M. Szántó3, A.C. Dobrică4
1
Methods: The dental status of 250 patients (58.7% males and 41.2% Emergency County Hospital, Pathology Department, Romania,
2
females) with diverse destructive forms had been investigated. Morpho- Emergency County Hospital, Radiology Department, Romania,
3
histological object: 10 biopsies of dentin with hematoxylin and eosin Emergency County Hospital, Pneumology Department, Romania,
4
staining (Van Gieson's and Weigert's stain). Bacterioscopic study: saliva Emergency County Hospital, Thoracic Surgery Department, Romania
of 15 patients stained with Fuxin by Gram's and Ziehl-Nielson/
Results: Morpho-histological studies of microscopies of hard tissues of Background & Objectives: Malignant mesothelioma is an inva-
teeth demonstrated that polymorphism of cell-tissue disorders, including sive and fatal neoplasm that arises from mesothelium, in general
distrophy of dentin and enamel structures of odontoblasts, where between after decades of asbestos exposure. It is considered a disease of the
the layers of dystrophic epithelium and layers of inflammatory tissue elderly, but rarely is diagnosed in patients under 40 years. These
should be noted to traced dystrophy of enamel structures and dentin patients may have an increased genetic predisposition to develop-
layers. In the smears-prints taken from the dorsal surface of the tongue, ing mesothelioma or may have environmental exposures to carci-
mycobacteria tuberculosis was not detected, however, squamous epithe- nogenic mineral fibers from an early age.
lial cells were found, as well as single layers of epithelial desquamated Methods: We present a case of a 31 years old, healthcare worker female,
cells, among which inflammatory cell elements were revealed. who was admitted to the Pneumology Department with dry cough, short-
Microscopic bacterioscopy in smears prepared from the saliva of patients ness of breath, night sweats, chills and severe asthenia. Her medical
with destructive forms of tuberculosis abundant accumulation of myco- history was no significat, excepting that 10 month earlier she gave birth
bacterium of dark pink color, merged in the form of lumps were detected. to a child, since than she had intermittent brownish vaginal secretion.
Conclusion: Results: On the CT scan multiple pleuro-pulmonary, mediastinal and
paravertebral lesions was described with 75x48x40 mm in greatest di-
mension, without any abnormality at the abdominal or pelvic organs. A
1. The presence of mycobacteria in saliva obliges dentists to adhere to
lymphoproliferative or a metastatic disease with unknown primary was
caution and strict observance of all protection measures during the
suspected. The gynaecological examination and the serum HCG level
examination of the oral cavity.
was normal. A pleuro-pulmonary biopsy was performed and the histo-
2. The results showed the importance of comprehensive studies of pathological examination revealed a partially necrotic tumour with solid
patients with pulmonary tuberculosis to assess the differential architecture, composed of small to medium sized epithelioid cells, with
diagnosic values in the dental aspect. eosinophilic and clear cytoplasm, mild to moderately pleomorphic round
nuclei, some of them hyperchromatic, some with vesicular chromatin and
prominent eosinophilic nucleoli. A few cells presented intranuclear inclu-
E-PS-22-028 sions. In the stroma a PAS positive material was present, as well as
Morphological features of the pulmonary sequestration numerous psammoma bodies. After the conventional histologic examina-
M. Rybakova1, I. Kuznetsova1, E. Markusevich1 tion a series of differential diagnoses were listed and the pathological
1
Pavlov First Saint Petersburg State Medical University, Russia examination was completed with immunohistochemical study. After the
interpretation of the immunohistochemical reactions a final diagnosis of
Background & Objectives: This study aimed to analyse clinico- epithelioid malignant mesothelioma was confirmed.
morphological features of pulmonary sequestration (PS). Conclusion: Malignant mesothelioma is a very rare, aggressive malignan-
Methods: We analysed clinical data and examined surgical specimens from 3 cy, commonly associated with asbestos exposure. Our patient could not
patients with the diagnosis of intralobar PS (in 2 cases aberrant vessels were prove any occupational origin for the asbestos exposition, but she con-
revealed during surgery, in 1 case – on CT with angiography).H&E, Ziehl– firmed that in every year at the winter time the heating of the house she
Neelsen and Van Gieson's stains were used for histopathological examination. lived in her child- and early adulthood was provided by an asbestos-based
Results: Patients’ meanage was 40±3years. Patients suffered from repeat- radiator. If the exposure to the asbestos mineral fiber can not be confirmed,
ed pneumonias, dry cough and episodic chest pains and hemoptysis. the presence of the germline BAP-1 mutation should be investigated. The
Macroscopically, lung specimens showed multiple variably sized cysts psammoma bodies are much more frequently reported in peritoneal meso-
separated by grossly normal lung parenchyma. Microscopic changes thelioma, their presence in the pleura are quite uncommon.
 Virchows Arch

E-PS-22-031 E-PS-22-034
Primary pulmonary synovial sarcoma: a report of three cases con- Clinico-pathological features of primary pulmonary hepatoid adeno-
firmed by fluorescence in situ hybridisation carcinoma (PPHAC): an under-recognised and aggressive lung neo-
I. Savic1, L. Simic2, M. Ninkovic2, G. Djuricic2, D. Ristic2, J. Sopta1 plasm with distinct immunophenotype (CK7-pos/HepPar1-pos/
1
Institute of Pathology, Medical Faculty, University of Belgrade, Serbia, TTF1-neg)
2
Institute for Oncology and Radiology, Belgrade, Serbia K. Varshney1, R. Kaushal1, N. Mittal1, T. Pai1, A. Janu1, A. Joshi1, J.
Agarwal1, K. Prabhash1, C. Pramesh1
1
Background & Objectives: Primary pulmonary synovial sarcoma is Tata Memorial Centre, India
extremely rare and aggressive neoplasm, comprising 0.3-1.3% of all lung
malignancies. Background & Objectives: Primary pulmonary hepatoid adenocarcino-
Methods: Here, we present three cases of primary pulmonary synovial ma (PPHAC) is a rare, aggressive neoplasm. Till date, it has failed to
sarcoma diagnosed at the tertiary institution. establish a distinct place in WHO classification for lung tumours. We
Results: Our patients were two males and one female age 20y/o, 67y/o and hereby, present the clinico-pathological spectrum of PPHAC.
56y/o respectively. They all presented with cough and chest pain. After im- Methods: PPHAC diagnosed between 2012-18 were retrieved from pa-
aging methods, tumour masses were found in their lungs. Tumour dimensions thology archives. Cases with known extra-thoracic primary were exclud-
on CT scans were >10cm in diameter. They were all initialy diagnosed as a ed. Clinico-radiological details were recorded and histopathological fea-
primary epithelial tumours in the lungs. Pathology specimens were sent for tures were reviewed.
revision in our institution. Microscopically, all tumours consisted of mono- Results: A total of 45 cases of PPHAC were recognized. Exclusive pre-
morphic, elongated spindle cells aranged in fascicular and dominance for males (43/45) and smokers (39/40) with median age of 55
hemangiopericytoma-like pattern with hyperchomatic nuclei. Area of necro- years (range 43–78 years) was noted. Tumour was predominantly located
sis, hemorrhage and moderate/intensive neoangiogenesis was noted. in upper lobe [(N=32/45(71%)] and ranged from 3cm – 11cm in size.
Differential diagnoses included other lung mesenchymal tumours: SFT, Mediastinal lymph nodes were enlarged in 78% (35/45). AFP levels were
MPNST, ES, as well as metastases outside the lung. Immunohistochemically, raised in 1/3 cases. Histopathological examination, revealed predomi-
spindle cells were positive for: TLE-1, vimentin and bcl2. EMA, CD99 and nantly solid (n=20) and trabecular pattern (n=12). Tumour cells were
cytokeratin were positive in 2 of 3 cases. FISH was performed in all cases large polygonal with abundant eosinophilic to clear cytoplasm in
which showed positive results in SS18 gene rearrangment. After complete 89%(40/45) cases. IHC showed a consistent and distinctive
staging, all cases were diagnosed as primary pulmonary synovial sarcoma. In immunoprofile i.e. CK7+/HepPar-1+/TTF1-in all 45 cases. Molecular
follow-up one patient developed systemic metastases. Two other patients evaluation (n=25) revealed consistent negativity for EGFR mutations,
were metastases free. They are all alive. EML4-ALK, ROS1 gene rearrangements and MET amplification in all
Conclusion: Primary pulmonary synovial sarcoma should be consid- except two cases (one with EGFR exon19 mutation and other with MET
ered in differential diagnosis of spindle and round blue cell tumours. Amplification). Chemo-radiotherapy (n=25) was the main treatment mo-
In that case, FISH could be very significant diagnostic tool. dality. Surgical resection was possible in only 4 cases. Median follow up
was 12 months (range: 2 months – 5 years) and 8 patients (24%)
succumbed within six months of diagnosis. Almost half of the patients
E-PS-22-032 (22/45) had metastatic disease at presentation (16 -skeletal and 8-both
Tissue preservation in non-small cell lung cancer (NSCLC) - a major visceral and skeletal metastases).
quality parameter Conclusion: PPHAC is emerging as a distinctive, highly aggressive,
T. Neuman1, T. Graziani2, G. Vainer1 under-recognised entity which occurs exclusively in smoker males. In
1
The Hebrew University - Hadassah Medical Center, Jerusalem, Israel, view of consistent Hep-Par1 positivity and TTF1 negativity, it may rep-
2
The Technion Medical School, Haifa, Israel resent a potential diagnostic pitfall.

Background & Objectives: Tissue handling in NSCLC is challenging as

the samples are tiny and the required information beside the diagnosis is E-PS-22-035
wide (i.e. immunoprofiling, PD-L1 status, genetic analyses). The ability PDL-1 in EBUS-TBNA material: a retrospective study of results in
to maximize information gained from limited samples is a major quality 127 patients and review of the literature
parameter for pathology departments; however, data on what are the A. Sobrino Prados1, R.I. Bermudez Cameo1, R. Álvarez Alegret1, L.
optimised utilization parameters is absent. Ferrando Lamana1, P. Gambó Grasa1, A. Valero Torres1, M. García
Methods: We developed a specific protocol for tissue handling in lung García1, J.J. Vengoechea Aragoncillo1, E. Mincholè Lapuente1, J.I.
biopsies. PD-L1 immunostains were performed in our institution between Franco Rubio1, M.J. Viso Soriano1
1
July 2016 and March 2019 for previously diagnosed NSCLC. Part of the Hospital Universitario Miguel Servet, Zaragoza, Spain
cases were in-house while others were referrals. In-house cases come
from two different hospitals. We analysed the utilization parameters of Background & Objectives: Because lung cancer treatments are increas-
the different groups and compared them also to the utilization results in ing so much in the last years, we need to improve our knowledgment of
the Israeli early access program(2015-2016). diagnosis methods and its possibilities. Programmed death-ligand 1 (PD-
Results: Overall, 92/1176(7.82%) of the cases could not be determined for L1) is one of the last discoveries and its expresion in lung cancer has
PD-L1 due to lack of material. For in-house case 131(3.09%) could not be become crucial for the patients outcome. On the other hand,
determined compared to 795(10.46%) for the outside cases(p<0.0001, endobronchial ultrasound-transbronchial needle aspiration (EBUS-
Fisher's exact test). 35 specimens taken outside but diagnosed in our hos- TBNA) is a minimally invasive technic to diagnose and stadify lung
pital showed none who could not be determined. In the Israeli early access cancer, on which we can perform PDL-1 in order to have the information
program(all of them were referral cases) the rate was 11.55%. of its expression before the surgical excision.
Conclusion: Outside cases show ~X4 more undeterminable cases compared Methods: Using 127 EBUS-TBNA samples from a single institution
to the in-house cases. This is more likely due to the pathology lab perfor- (Universitary Hospital ‘Miguel Servet’ of Zaragoza) between 2018 and
mance as executing the entire processing yields similar cases even tissues 2019, we have analysed the incidence of the different types of lung can-
which are obtained in another hospital. Priority should be given to laboratories cer, age of diagnosis, gender and PDL-1 expression (PDL-1 IHC 22C3).
that can do both the diagnosis and the additional assays. A rate of 3% for Results: Out of 127 patients, 97 were males. 57 out of 127 patients
undeterminable cases is achievable. expressed PDL-1 in their EBUS-TBNA material. From our sample, the
Virchows Arch

predominant histologic type was adenocarcinoma (44,88%) and the sec- We measured PD-L1 expression (Tumour proportion score; 22C3 based
ond and third one, the squamous cell and microcitic lung cancer (28,34% LDT), EGFR mutations (COBAS or Oncomine 22 gene panel), ALK and
and 7,87% respectevely). PDL-1 was equivalently expressed in adeno- ROS1 were screened by IHC, and confirmatory FISH was done if needed.
carcinoma and squamous carcinoma, whithout relevant differencies be- Results: We recorded a PD-L1 TPS of ≥50% in 30.27% (244/806 cases),
tween both groups. 34 out of 127 patients died, 38, 2% of them suffering EGFR activating mutations in 20.03% (122/609 cases; del Ex19 57.6%,
from an adenocarcinoma. L858R 29.6%, Others 12.8%), ALK positivity in 4.38% (21/484 cases),
Conclusion: In our sample, a clear male predominance existed but there and ROS1 positivity in 2.13% (9/421 cases).
were no significative differencies between PDL-1 expression neither in No occurrence of EGFR mutation, ALK or ROS1 found.
the different histological lung cancers nor in gender predilection. TPS of ≥50% shows correlation to del Ex19 (70%) while TPS of < 1%
Anyway, further research about PDL-1 and its expression is needed for shows correlation to L858R (38.29%).
offering the best diagnosis and treatment options for patients. Overall, this common drive mutations express PD-L1 TPS of ≥50% in
24.59% (30/122) for EGFR, 33.33% (7/21) for ALK and 55.55% for
ROS1 (5/9).
E-PS-22-036 Conclusion: A TPS of ≥50% shows less overall prevalence with EGFR
Lower BRMS1 expression is associated with high grade histologic alterations but with specific affinity to different exons. However, ALK
subtypes in lung adenocarcinomas and ROS1 shows higher prevalence for TPS ≥50%.
P. Bulutay1, P. Firat2, H. Zeren3, S. Erus4, S. Tanju4, Ů Dilege4
1
Koç University School of Medicine, Pathology department, Turkey,
2
Koç University School of Medicine, Pathology department, Turkey, E-PS-22-039
3
Acibadem University School of Medicine, Pathology department, Turkey, A 1-year study of pathological aspects and incidence rate of pulmo-
4
Koç University School of Medicine, Thoracic surgery department, Turkey nary carcinomas
F. Neacsu1, M. Sajin1, G. Simion1
1
Background & Objectives: Breast cancer metastasis suppressor1 Carol Davila University of Medicine and Pharmacy of Bucharest,
(BRMS-1) shows a decreased expression in some tumour types which Romania
is related with poor prognosis. The aim of this study is to investigate the
relationship between BRMS1 expression and histopathologic prognostic Background & Objectives: Malignant lung tumours have the highest
parameters in lung adenocarcinomas. rate of deaths caused by cancer worldwide. Most of the pulmonary ma-
Methods: Tissue microarrays prepared from 147 lung adenocarcinoma lignant tumours are carcinomas.
resections were studied. Histologic subtypes were given by consensus of The histologic types are: adenocarcinoma, squamous cell carcinoma,
three pathologists, intratumoral BRMS-1 immunostaining was scored due small cell carcinoma and large cell carcinoma. Between 1977-1981, the
to intensity (0-3). For statistical analysis 0-1 and 2-3 were grouped to- most common histologic type was squamous carcinoma(30%) followed
gether as low and high expression, respectively. The results were com- by adenocarcinoma(<30%).
pared with histopathologic subtypes (lepidic, acinar, papillary, mucinous Methods: This study aims to determine the incidence rate of primary lung
patterns were grouped as low/intermediate grade; micropapillary, solid, carcinoma among patients diagnosed between May 2017 - May 2018 at
cribriform patterns were grouped as high grade), T/N stages, the University Emergency Hospital from Bucharest, Romania.
lymphovascular and pleural invasion The diagnoses were established based on gross, microscopic and immu-
Results: 273 microarray cores from 147 patients were analysed. nohistochemical examination.
Histologic subtypes were composed of 2 lepidic, 77 acinar, 35 papillary, Results: Among the 43 patients diagnosed with lung cancer, 15 were
39 micropapillary, 96 solid, 16 cribriform and 8 mucinous. BRMS1 ex- females and 28 males, aged 41-81 years.
pression was high in 84%, and low in 16% of cores. 19,1% of high grade The most common histologic types were: adenocarcinoma(72,1%), squa-
and 5,7% low grade histologic subtypes showed low BRMS1 expression mous cell carcinoma(23,25%), small cell carcinoma(2,3%) and lung neu-
and this difference was statistically significant(p:0,00). No significant roendocrine tumour(2,3%).
relation was detected between BRMS1 expression and other histopatho- 30,23% of patients presented with lymph nodes invasion with patterns of
logic parameters evaluated in this study. adenocarcinoma(76,9%), squamous cell carcinoma (15,38%) and small
Conclusion: Loss of BRMS-1 expression was more frequent in cell carcinoma(7,7%).
micropapillary, solid and cribriform comparing to lepidic, acinar, papil- Pleural invasion was found in 9 patients(20,9%): 8 with adenocarci-
lary and mucinous adenocarcinomas. The relation between low BRMS-1 nomas, 1 with squamous cell carcinoma.
expression and poor prognostic subtypes was significant. However, this The tumour invasion in the mediastinum was found in 7 patients.
study didn’t show any relation with other prognostic parameters, most Conclusion: This study focuses on the pathological aspects and the incidence
importantly with lymph node metastases. Further studies on larger series rate of pulmonary carcinomas. Even though the study is done on a short period
including also survival analysis are needed. of time, it can be seen that adenocarcinomas incidence rate is increasing.

E-PS-22-037 E-PS-22-040
Correlation between EGFR, ALK and ROS1 and 22C3-PD-L1 Pulmonary sclerosing epithelioid fibrosarcoma: a case report and
expression in lung adenocarcinoma review of literature
T. Neuman1, G. Vainer1 J. Martin Lopez1, J.L. Rodriguez Carrillo1, M. Colomès1, E. Verdu
1
The Hebrew University - Hadassah Medical Center, Jerusalem, Israel Martin1, H. Tavarez Alvarez1, C. Salas Anton1
1
Background & Objectives: Modern treatment of lung adenocarcinoma Department of Pathology. Hospital Universitario Puerta de Hierro,
requires the analysis of programmed death ligand 1 (PD-L1), EGFR, Spain
ALK and ROS1.
This facilitate the selection of biological, first-line therapies in advanced Background & Objectives: Sclerosing Epithelioid Fibrosarcoma
lung cancer. However, the frequency of overlap of these biomarkers in (SEF) is a rare neoplasm that usually affects deep soft tissues in lower
routine clinical practice is not well reported. extremities and less frequently head and neck region. The primary
Methods: Between July 2016 and March 2019, 820 lung adenocarcino- visceral origin is rare with similar morphology: diffuse areas of col-
ma patients were analysed at the Hadassah Medical Center. lagen sclerosis with epithelioid cells arranged in cords or nests.
 Virchows Arch

Commonly, the immunohistochemical techniques are positive for In our case, consisting in edema with hyaline membranes lining the alve-
vimentin and MUC4 and in some cases has been associated with olar spaces. In addition to the clinical and immunological findings we
FUS gene alterations. established a diagnosis of TRALI.
Methods: We report a case of pulmonary SEF with mediastinal lymph
node involvement and discuss it in the context of the current literature.
Sunday, 8 September 2019 – Wednesday, 11 September 2019
Results: A 55-year-old male admitted to the coronary care unit with a
E-PS-23 | Soft Tissue and Bone Pathology
diagnosis of acute coronary syndrome showed in radiological studies a
26 mm lung lesion in the right lower lobe. After his clinical recovery, an
intraoperative wedge resection was performed. E-PS-23-001
Histopathological examination showed epithelioid cells arranged in Tenosynovial giant cell tumour, localised type with extensive
cords and nests within diffuse areas of sclerosis. The cytological chondroid metaplasia: a case report with immunohistochemical
detail showed small to medium-sized epithelioid cells with clear to and molecular genetic analysis
eosinophilic cytoplasm and small nucleoli identifying frequent mito- R. Maruyama1, M. Nagase1, A. Araki2, N. Ishikawa1, N. Nagano1, N.
sis. The immunohistochemical study was diffusely positive for Yamagami1, S. Yamamoto1
1
vimentin, BCL2, CD99 and MUC4; with isolated positivity for Shimane University School of Medicine, Japan, 2 Institute of
EMA. CK AE1-AE3, S100, HMB45, CD34, actin, desmin were neg- Neurology, Medical University of Vienna, Austria,
ative. The Ki67 proliferative index was 8%. FUS testing was nega-
tive. In regional lymphadenectomy, one lymph node was Background & Objectives: Tenosynovial giant cell tumour (TSGCT) is
involvement. divided into localized and diffuse types. In contrast to diffuse type, it is
After the diagnosis, a detailed clinical examination and a PET-CT scan easy for experienced pathologists to render a diagnosis of TSGCTs of
were performed to exclude a soft tissue origin. localized type. However, when it shows extensive chondroid metaplasia
Conclusion: Sclerosing epithelioid fibrosarcoma is rare arising from the which has been reported almost only in diffuse type, it may be extremely
lung. Visceral presentation is usually due to a metastasis from a soft tissue difficult to differentiate from chondroid tumours. We have experienced
origin. Immunohistochemical staining with MUC4 is specific and in a such a case and histological, immunohistochemical and molecular genetic
percentage of cases it is associated with alterations on FUS gene. findings of the tumour are presented.
Methods: A 72-year-old man presented with a well circumscribed
subcutaneous tumour on his left hand. He first noticed the lesion 7
E-PS-22-041 years prior to admission with a gradual increase in size since its
Transfusion-related acute lung injury: clinical, role of HLA class I onset. Clinical and radiological findings indicated TSGCT of local-
antibodies and histopathological features of a case report ized type and the tumour was excised. We performed gross and
J. Martin Lopez1, L. Nuñez Martín Buitrago2, S. Garrido Paniagua2, J.L. microscopic examinations, immunohistochemistry including clus-
Rodriguez Carrillo1, M. Colomes Iess1, E. Verdu Martín1, H. Tavares terin, CD68, CD163, CD45, S-100 and podoplanin, and fluorescent
Alvarez1, A. Beneitez Fernandez2, I. Krsnik2, J.L. Bueno Cabrera2, R. in situ hybridization (FISH) on formalin-fixed paraffin embedded
Cabrera Marin2, C. Salas Anton1 sections using custom-made probes.
1
Department of Pathology, Hospital Universitario Puerta de Hierro, Results: Grossly, the excised specimen consisted of a well circumscribed
Spain, 2 Department of Haematology, Hospital Universitario Puerta de tumour, which was about 2.5cm in maximum diameter. Microscopically,
Hierro, Spain the tumour showed a vaguely lobular pattern of growth with extensive
chondroid appearance with low power view. With high power examina-
Background & Objectives: Transfusion-related acute lung injury tion, the lobules with chondroid stroma were surrounded by large mono-
(TRALI) is an uncommon clinical outcome characterised by the rapid nuclear cells, osteoclastic multinucleated giant cells and smaller
onset of respiratory distress early after transfusion. Its diagnosis is based histiocytoid cells. Immunohistochemically, the large mononuclear cells
on clinical and radiographic changes that are indistinguishable from acute were positive with clusterin, and FISH demonstrated a CSF1-COL6A3
lung injury/acute respiratory distress syndrome (ALI/ARDS). TRALI is fusion gene.
presumed to be a form of ALI/ARDS; however, it differs in its triggering Conclusion: It is necessary to be aware that not only diffuse type but the
events and associated mortality. localized type of TSGCT can exhibit extensive chondroid features. IHC
Methods: We describe a case report of TRALI with all the clinical and and/or FISH analysis should be recommended to differentiate it from
histopathological details. cartilaginous tumours. We suspect there is a possibility that at least some
Results: A 59-year-old woman with personal history of cirrhosis and soft tissue chondromas of the hands are reclassified as TSGCT with ex-
hepatic encephalopathy went to the emergency room due to clinical tensive chondroid metaplasia.
worsening with sudden vaginal bleeding. Because thrombocytope-
nia a pool of platelets and a plasma unit were transfused. Two hours
after presented with severe hypoxemia and chest CT scan reveals a E-PS-23-002
diffuse pulmonary infiltrates. After respiratory failure biopsies were Analysis of molecular alterations in undifferentiated pleomorphic
taken by fibrobronchoscopy. The histopathological study showed an sarcomas
acute phase of ALI with pulmonary edema and hyaline membranes G. Raskin1, E. Preobrazhenskaya2, O. Gorustovich2, V. Heinshtein3, K.
lining the alveolar spaces with granulocyte aggregation within the Shelekhova3, E. Suspitsin4
pulmonary microvasculature. After histological diagnosis of ALI 1
Academic A.M. Granov Scientific Center for Radiology and Surgical
excluding other morphologic etiologies, clinical worsening and pos- Technology, Russia, 2 N.N. Petrov Institute of Oncology, Russia, 3 City
itive results of anti-HLA Class IA and IB IgG Antibodies, treatment Cancer Center, Russia, 4 St.-Petersburg Paediatric Medical University,
with methylprednisolone was initiated. Despite this, patient dies. Russia
Conclusion: TRALI is an uncommon adverse side effect related with
transfusion. TRALI case reports describe a classical morphology of Background & Objectives: Undifferentiated pleomorphic sarcoma
acute phase of ALI, or pulmonary edema with neutrophil accumula- (UPS) is an aggressive type of tumour; it is thought to arise from primitive
tion within alveolar capillaries or even just neutrophils within alveo- mesenchymal stem cells yet there is no consensus about its origin. Many
lar spaces. researchers believe that it cannot be considered a separate nosology but
Virchows Arch

1
rather unites a group of mesenchymal tumours comprised of cells which Department of Diagnostic Pathology, Hyogo Cancer Center, Japan,
2
progenitors cannot be clearly established. The objective of the study was Pathology for Regional Communication, Kobe University School of
to investigate the spectrum of molecular alterations in UPS. Medicine, Japan, 3 Department of Dermatology, Hyogo Cancer Center,
Methods: Tumour cDNA samples of 41 patients with UPS have Japan
been collected. Copy number of CDK4, MYCN, MDM2, HER2,
KIT, and PDGFRA genes was analysed using digital droplet PCR. Background & Objectives: Cellular neurothekeoma (CN) is a rare, cu-
Presence of 12 variants of fusion transcripts involving EWS (EWS taneous mesenchymal tumour of unknown histogenesis. Despite occa-
ex7/FLI ex6, EWS ex7/FLI ex5, EWS ex10/FLI ex6, EWS ex9/FLI sional worrisome features, this tumour follows a benign clinical course.
ex4, EWS ex10/FLI ex5, EWS ex8/FLI ex6, EWS ex10/FLI ex8, We herein report two cases of CN with anaplastic features, one of which
EWS ex7/FLI ex8, EWS ex7/ERG ex10, EWS ex7/ETV1 ex12, behaved aggressively.
EWS ex7/ETV4 ex9, EWS ex7/FEV ex2) was assessed using quan- Methods: Case 1. A 73-year-old female complained of a subcutaneous
titative real-time PCR. mass of 55 mm in diameter in the left upper arm, which was widely
Results: Amplification of CDK4 was observed in 18 (44%), MYCN – in resected. During the follow-up period of four years, the tumour recurred
nine (22%), and MDM2 – in one (2%) patient, respectively. Seven UPS two times. Case 2. A 70-year-old female noticed a subcutaneous mass,
samples (17%) demonstrated simultaneous amplification of CDK4 and 70 mm in size, located in the left subscapular region and underwent a
MYCN, and one sample – of CDK4 and MDM2. No increase in HER2, wide excision of the tumour.
KIT, or PDGFRA copy number was detected. 3 samples (7%) had EWS Results: Both tumours were located in dermis and subcutis and com-
ex7/ETV1 ex12 translocation. posed of epithelioid to short-spindle tumour cells arranged in clusters,
Conclusion: CDK4 and MYCN amplifications are commonly observed nests, and fascicles. Nuclear pleomorphism was noted in some areas
in undifferentiated pleomorphic sarcomas. Sarcoma-specific transloca- and mitotic figures, including atypical ones, were frequent: 10 (Case 1)
tions may also be found in a small fraction of UPS patients. and 20 (Case 2) per 10 HPF. Immunohistochemically, tumour cells in
both cases were diffusely positive for NKI-C3, MITF and CD10, but
The study was supported by the Russian Science Foundation grant 18-15- negative for S-100 protein, SOX10, and HMB45. Ki-67 labeling indices
00256. were 22% (case 1) and 45% (case 2).
Conclusion: The pathologic and immunohistochemical features of the
present two cases were basically consistent with those of CN. Cellular
E-PS-23-003 anaplasia, increased proliferative activity and repeated recurrences in case
Intraosseous schwannoma of the rib with cortical breakdown; resem- 1, however, may suggest the presence of malignant counterpart of CN.
bling chondrosarcoma radiologically
K.B. Lee1, K.S. Kwack2, S.J. Haam3
1
Pathology, Ajou University Hospital, Republic of Korea, 2 Radiology, E-PS-23-005
Ajou University Hospital, Republic of Korea, 3 Thoracic & Denosumab has limited therapeutic effect on giant cell tumour of
Cardiovascular Surgery, Ajou University Hospital, Republic of Korea bone: a study of 7 recurrent cases
I. Kato1, M. Furuya1, Y. Kawabata2, M. Takeyama2, K. Hayashida2, R.
Background & Objectives: Intraosseous schwannomas of rib are Tanaka3, K. Ohashi1
1
extremely rare, and only four cases have been reported. We experi- Yokohama City University, Japan, 2 Orthopaedic Surgery, Yokohama
enced a case of intraosseous schwannoma arising in the rib, which City University Hospital, Japan, 3 Medical Mycology Research Center,
suggested chondrosarcoma radiologically by its aggressive behavior. Chiba University, Japan,
We present this case by its rarity and radiological differential
diagnosis. Background & Objectives: Denosumab, a human monoclonal antibody
Methods: A 58-year-old male was admitted due to a rib mass. He had a against RANKL, has been introduced into the therapy of giant cell tumour of
history of trauma three years ago at this area. He complained of pain. Plain X- bone (GCTB). We have recently reported that the H3.3G34W(mutation spe-
ray showed an expansile osteolytic lesion at the anterior arc of right seventh cific marker)-positive osteoblastic tumour cells survive denosumab therapy in
rib. Computed tomography of the chest revealed a 3.6cm sized mass with contrast to the dramatic histological alterations including disappearance of
curved calcification peripherally. Cortical breakdown was noted, resulting in giant cells and formation of woven bone (Histopathology. 2018;72:914-22).
soft tissue mass formation. Radiologic impression was low grade The histology of recurrent case has not been reported so far.
chondrosarcoma. There was no lung invasion. Wide excision was done. Methods: We studied 7 patients with recurrent GCTB. All patients
Results: Grossly, the tumour showed an expanding growth into the sur- underwent curettage with neo-adjuvant (5 to 11 times) and adjuvant (4
rounding soft tissue with cortical breakdown. Margin of the mass was to 8 times) denosumab therapy. The typical histology (mixture of
solid, but most central area revealed multilocular hemorrhagic cysts. fibrohistiocytic lesion and reticular woven bone) was confirmed. All pa-
Microscopically, the tumour was composed of spindle cells with Antoni tients underwent re-curettage after additional or no denosumab therapy.
A and B areas.Verocay bodies were evident. Tumour cells infiltrated into Histological and immunohistochemical findings were investigated.
the cortical bone. Immunohistochemical staining for S-100 protein was Results: Seven patients experienced local recurrence in 11-43
positive. Pathological diagnosis was intraosseous schwannoma with an- months after initial curettage. The histological appearances of re-
eurysmal bone cystic change. curettage were mixture of conventional GCTB and typical
Conclusion: Schwannoma is a benign tumour, but when occurs in the rib, denosumab-treated GCTB with variable proportion. The proportion
it infiltrates into the cortical bone and results in cortical breakdown and of two components seemed to correlate with the duration of the
soft tissue extension. This behavior makes a suggestion of chondrosarco- latest denosumab therapy (0 to 4 times) just before re-curettage.
ma and other malignant tumours radiologically. An extraosseous mass was observed in one case, which was com-
The study was supported by the Russian Science Foundation grant 18-15- posed of reticular woven bone with focal conventional GCTB his-
00256. tology. Constantly, H3.3G34W immunohistochemistry was diffusely
positive in all cases.
Conclusion: Denosumab led to dramatic histological alterations not only
E-PS-23-004 in initial GCTBs but also in recurrent and extraosseous lesions; however,
Cellular neurothekeoma with anaplastic features: report of two cases actual therapeutic effect appeared to be limited. Pathologists should care-
T. Hirose1,2, T. Takai3 fully evaluate anti-tumour effects of denosumab in the treated specimens.
 Virchows Arch

E-PS-23-006 2) β-catenin nuclear expression was seen in 20 of 22 cases (91%).

Cutaneous giant cell tumour of the scalp 3) Correlation between β-catenin nuclear expression and WLS expres-
S. Sotiriou1, A. Fragoudi2, P. Hytiroglou1 sion is identified in most SS cases. All 4 cases of weak WLS expression
1
Pathology Department, Faculty of Medicine, Aristotle University of are accompanied by β-catenin nuclear expression; however, 2 of 18 SS
Thessaloniki, Greece, 2 Anatomic Pathology Laboratory, Drama, Greece cases with moderate to strong WLS expression lack aberrant β-catenin
nuclear expression.
Background & Objectives: Giant cell tumours of soft tissue (GCT-ST) Conclusion: This is a novel study characterising both WLS expression
are rare neoplasms; few have been described in the head and neck. and β-catenin nuclear localisation in SS patients. Our results show that
Morphologically, they are identical with the more common giant cell the majority of SS tumours overexpressed WLS with visible β-catenin
tumour of bone (GCT-B). In contrast to the majority of GCT-Bs, which nuclear localisation, suggesting a possible correlation of WLS overex-
are characterised by point mutations of the H3F3A gene, GCT-STs do not pression and β-catenin nuclear localisation. Specific SS cases where
bear this molecular aberration. The aim of this case report is to raise WLS is overexpressed with no β-catenin nuclear localisation observed
awareness regarding this entity and to point out the importance of the could be attributed to the activation of the non-canonical Wnt pathway.
differential diagnosis. Hence inhibition of WLS is hypothesised to have a leverage in SS treat-
Methods: An 87-year-old woman has undergone resection of a nodule of ment over suppression of downstream canonical pathway. Our findings
the scalp, which caused ulceration of the overlying skin. Tissue sections pave an avenue for this possibility of novel SS treatment strategy. Much
were stained with H&E and immunohistochemical stains for vimentin, further work is warranted to reveal possible mechanistic insights to val-
CD68, and smooth muscle actin (SMA). idate our results.
Results: Microscopically, the nodule represented a well-circumscribed
tumour of the dermis and the subcutaneous tissue, characterised by a
dense biphenotypic cellular population composed of a mixture of round E-PS-23-009
to oval mononuclear cells and regularly distributed osteoclast-like giant Cancer stem cell markers expression in soft tissue sarcoma and their
cells embedded in a highly vascularized stroma. Atypia was absent. On clinicopathologic siginificance
immunohistochemical stains, the osteoclast-like giant cells showed im- U. Jo1, K. Cho2, J.S. Song1
1
munoreactivity for vimentin, and CD68 and the mononuclear cells for Department of Pathology, University of Ulsan College of Medicine,
vimentin, and SMA. Asan Medical Center, Republic of Korea, 2 Department of Pathology,
Conclusion: Based on the histological findings, and the absence of any Asan Medical Center, Republic of Korea
bone lesion or the history of GCT-B, our final diagnosis was that of a
GCT-ST. GCT-STs should be differentiated from metastatic GCT-B, but Background & Objectives: Soft tissue sarcomas (STSs) are rare hetero-
also from other cutaneous giant cell-rich neoplasms, such as plexiform geneous mesenchymal malignant tumours and recent studies have shown
fibrohistiocytic tumour, and atypical fibroxanthoma . Clinicopathological an association of cancer stem cells (CSCs) with STSs pathogenesis.
correlation and immunohistochemical/molecular assays are crucial in the However, the clinicopathologic role of CSCs in the STSs is still poorly
differential diagnosis. characterised. Herein, we investigate the expression of CSCs markers
including SOX2, OCT4 and Nanog in the STSs and examine the prog-
nostic impact of these proteins.
E-PS-23-008 Methods: Immunohistochemistry was performed on tissue microarray
β-catenin nuclear localisation and Wntless expression in synovial using 262 cases of STSs and the results were analysed with clinicopath-
sarcoma ologic parameters.
V.K. Lee1, S.S.S. Hue1 Results: 72.1% (230/262), 26.6% (85/262) and 29.2% (93/262) of
1
National University Hospital, Singapore STSs showed immunopositivity for SOX2, OCT4 and Nanog, re-
spectively. Most frequent SOX2-expression tumour was Ewing sar-
Background & Objectives: Wnt pathway is an extensively featured coma (80%), followed by malignant peripheral nerve sheath tumour
signalling pathway that is known for its role in embryonic develop- (MPNST, 71.4%) and pleomorphic liposarcoma (57.1%). Most fre-
ment, tissue homeostasis and oncogenesis. Recent studies have im- quent Nanog-expression tumour was undifferentiated pleomorphic
plicated the role of constitutively active Wnt/β-catenin signalling in sarcoma (83.3%), followed by osteosarcoma (66.7%) and MPNST
synovial sarcoma (SS) tumourigenesis. Although the activation of (57.1%). SOX2 and Nanog were correlated with the higher
canonical Wnt/β-catenin pathway has been investigated in SS, the FNCLCC grade (p = 0.024 and p <0.001, respectively), but
role of Wntless (WLS), a protein found upstream of Wnt pathway OCT4 wasn’t (p= 0.239). Three of these proteins were not correlat-
affecting both canonical and non-canonical Wnt ligands, has not ed with each other (SOX2 vs Nanog, p=0.217; SOX2 vs OCT4, p=
been well explored. In this study, we evaluated the protein expres- 0.750; Nanog vs OCT4, p =0.767). Overall survival (OS) according
sion of WLS in SS by immunohistochemistry (IHC) on a tissue to SOX2, OCT4 and Nanog showed also no statistical significance
microarray (TMA) block consisting of SS patient samples. (p = 0.759, p = 0.053, and p = 0.427, log-rank, respectively) al-
Methods: A total of 72 SS cases from 2000 - 2016 were identified from though OCT4-expressed group had a tendency to poor OS.
the database record of the Department of Pathology, National University Conclusion: CSCs markers were expressed differently according to tu-
Hospital (NUH). Suitable cases with sufficient tissue material were sub- mour types. These findings potentiate the targeting of these CSCs for
sequently included for TMA construction (n=22 per TMA set). Two sets novel therapeutic interventions in STSs.
of TMAs were immunohistochemically stained with YJ5 (Wntless / WLS
antibody) and β-catenin. Using a three-tiered scoring system, staining
expressions of these antibodies were quantitatively and qualitatively E-PS-23-010
reviewed and scored by two histopathologists. Clear cell chondrosarcoma of the Rib: a rare tumour in an uncom-
Results: 1) WLS expression was present in all samples (n=22), with mon location
4 cases (18.2%) exhibiting weak WLS staining, 8 cases (36.4%) D.F. Martins1,2, E. Rios3,4,5
1
exhibiting moderate staining and 10 cases (45.5%) exhibiting strong Department of Pathology of Centro Hospitalar Universitário São João,
staining. Thus, overall our results showed that the majority of SS Portugal, 2 Faculty of Medicine of the University of Porto, Portugal,
3
cases (81.8%) demonstrated significant expression (moderate to Department of Pathology, Centro Hospitalar de São João, Porto,
strong) of WLS protein. Portugal, 4 Department of Pathology, Faculty of Medicine of the
Virchows Arch

University of Porto (FMUP), Porto, Portugal, 5 Institute of Molecular Recurrence rate was of 80 % in positive margin cases and 25 % in neg-
Pathology and Immunology at the University of Porto (Ipatimup), ative margin cases. The difference was statistically significant
Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal (p=0,0039).
Metastasis occurrence was seen in 5 patients with positive margin and in 6
Background & Objectives: Clear cell chondrosarcoma (CC-CSA) is a patients with negative margins, the difference was statistically not signif-
rare, low-grade variant of chondrosarcoma, accounting for 2% of all icant (p= 0,83).
chondrosarcomas. It typically involves long bones, especially proximal Conclusion: 5-year overall survival was of 16 % in positive margin
femur and humerus. Rib involvement is exceedingly rare, with less than and 83% in negative margin cases. The difference was statistically
20 cases reported. We herein report an incidental finding of CC-CSA in significant (p=0,0028). In our study, positive surgical margins have
the rib. a strong adverse prognosis effect on local recurrence and 5-year
Methods: A 57-year-old male was found to have on chest X-ray a 3-cm overall survival. These findings justify a policy of surgical adequacy
nodular lesion in the third left rib, during preoperative evaluation for in soft tissue LMS.
inguinal hernia repair. Both thoracic computed tomography scan and
T2-weighted magnetic resonance revealed an expansile heterogeneous
rib lesion with indistinct margins. Wide resection of the lesion was E-PS-23-012
performed. Frequency of GNAS mutation in intramuscular myxoma
Results: Grossly an expansile, firm, tan-white to gray and glistening R. Erber1, R. Stöhr1, F. Haller1, A. Hartmann1, A. Agaimy1
1
lesion extending through the cortex and contained by the periosteum, Institute of Pathology, University Clinics Erlangen, Friedrich-Alexander
was seen. Histology showed sheets of large cells with clear-pink, vac- University Erlangen-Nürnberg, Erlangen, Germany
uolated cytoplasm and scattered osteoclasts surrounded by a promi-
nent osteoid-rich matrix. The tumour cells exhibited infiltrative Background & Objectives: Intramuscular myxoma (IMM) is a rare
growth pattern, encasing preexisting bone, and were diffusely positive benign lesion of the soft tissue that can arise sporadically or in patients
for S100 protein and focally for CK8/18. Final Diagnosis was CC- suffering from fibrous dysplasia (Mazabraud's syndrome). Mutation rates
CSA. At one-year follow-up the patient has no evidence of recurrent of the GNAS gene (20q13) described in literature range between 20 and
or metastatic disease. 83 % of IMM depending on method used.
Conclusion: Despite its rarity, CC-CSA can arise in the ribs be- Methods: We searched our archive for cases with the diagnosis of IMM.
coming a diagnostic challenge due to its morphologic features that Clinical and pathological parameters including results of diagnostic
often mimics other entities, like chondroblastoma, osteosarcoma GNAS gene mutation analysis were retrieved from our original reports.
and metastatic carcinoma. CC-CSA behaves as low-grade tumour All cases were reviewed to verify diagnosis.
and an accurate diagnosis is essential to ensure the most effective Results: 71.7 % of included IMM, mostly occurring in the thigh
and appropriate treatment, to minimize local recurrence (<20%). (55.6 %), were females (33/46). Mean age at diagnosis was 53.4
Yet, long term follow-up is required because even rare, metastases years, mean diameter 6.1 cm. IMM showed hypocellular myxoid
may occur up to 20 years following initial diagnosis. matrix with embedded spindle cells, scarceness of vessels, positiv-
ity of vimentin, variable CD34 positivity and negativity of MUC4.
Checkerboard like edema of surrounding muscle was a constant
E-PS-23-011 feature. Of 17 cases with successful GNAS mutation testing (per-
Prognosis impact of surgical margins quality in soft tissue formed at initial diagnostic workup), 3 harboured a GNAS muta-
leiomyosarcoma: a retrospective study of 40 cases tion (17.6 %).
D. Chiba1, S. Mestiri1, S. Chaieb1, T. Zahmoul2, S. Ben Khalifa1, S. Conclusion: In our study, the frequency of GNAS mutations lies
Yacoub1, N. Abdessayed1, B. Sriha1, M. Mokni1 within the lowest range of GNAS mutation frequency reported in
1
Department of Pathology, Farhat Hached Hospital, Tunisia, 2 Cancer literature. It has to be discussed whether GNAS mutations vary
Registry of the Tunisian Center, Tunisia according to different subsets (e.g. cellular) in the spectrum of in-
tramuscular myxomas or whether there is need for more sensitive
Background & Objectives: Soft tissue leiomyosarcomas (LMS) are mutation detection methods in these predominantly paucicellular
aggressive tumours and are difficult to treat. The prognosis is lesions.
poor, with survival rates among the lowest of all soft tissue
sarcomas.
Treatment is based on adequate surgical resection. E-PS-23-013
Our aim was to conduct a retrospective study of 40 cases of soft Lipoma arborescens of the knee, a rare tumour
tissue LMS retrieved at the Central Tunisia Cancer Registry to S.Y. Celik1, O. Ilhan Celik1, U. Canbek2, Y. Dere1
1
determine the prognostic impact of surgical margins quality on Mugla Sitki Kocman University, Faculty of Medicine, Department of
local recurrence, distant metastasis and 5-year overall survival in Pathology, Turkey, 2 Mugla Sitki Kocman University, Faculty of
soft tissue LMS. Medicine, Department of Orthopaedics, Turkey
Methods: We have reported retrospectively during a period of 25
years (1996- 2012) the patients with LMS that were diagnosed at Background & Objectives: Synovium is an unusual site for prima-
the pathology department of F. Hached hospital in Sousse, ry tumours most of which are benign. Lipoma Arborescens(LA) is
Tunisia. one of these rare benign tumours of the synovium. It’s a chronic,
We have classified the margins according to the recent dataset from the slowly progressive, intra-articular lesion characterised by villous,
royal college of pathologists that takes into account whether there is lipomatous proliferation of the synovium.
tumour at the cut edge (R1) or not(R0). Methods: A 72-year-old male suffering from furtive onset of pain-
The end-points of this study were 5-year overall survival, local recurrence less swelling of his left knee persisting for many years and follow-
and distant metastasis. ed by progressive pain with motion limitation was admitted to
Results: 5 patients who had initially metastasis at presentation did orthopaedics clinic. In physical examination diffuse suprapatellar
not undergo surgical treatment, surgical margins were intra-lesional swelling and tenderness were present without any calor and rubor.
in 15 patients (R1), and 20 patients had negative surgical margins All laboratory tests were within the normal range. Left knee mag-
(R0). netic resonance revealed hiperintense synovial thickening and
 Virchows Arch

presence of fatty mass in the joint cavity and especially in the multifocal. Multifocal lytic lesions are strongly suggestive of GCRG.
suprapatellar bursae. Nowadays it is an unusual clinical presentation since it is a lesion related
Results: Surgical synovectomy was performed and the material excised to the terminal stage of the bone remodelling process in prolonged
was 7x5x3cm in size, yelow, white in color. In the histopathological hyperparathyroidism.
examination diffuse, mature, uniform lipocytic proliferation without Methods: A fifty-year-old white woman reported to the Orthopedic
atypia was present in most of the material covered by papillary sinovial Department of our hospital with a pathological elbow fracture. Past med-
projections accompanying mononuclear inflamatory cells; so the lesion ical history includes hypertension and chronic renal failure (CRF), requir-
was diagnosed as LA. ing haemodialysis since 2010. Computed Axial Tomography (CAT) re-
Conclusion: LA (diffuse articular lipomatosis) can be seen in pa- vealed osteolytic lesions involving the distal humerus and proximal
tients aged between 9 and 68 years. It has 2 aetiological types femur.
depending on the age of onset and underlying precipitating con- Results: Surgical biopsy of the humerus lesion revealed brown
ditions. Primary type is less common, idiopathic and seen in spongy material, histologically characterised by large numbers of
younger ages in second/third decades. Secondary type is more multinucleated giant and spindle cells in a dense collagenous
common, generally seen in older-patients, associated with an un- background. These findings were histologically consistent with a
derlying chronic irritation, like degenerative disease, synovitis, diagnosis of GCT, however a serological evaluation revealed high
trauma and meniscal injury. Synovectomy is the treatment. levels of parathyroid hormone (PTH). Ultrasound confirmed bilat-
Recurrence is unusual and malign transformation is not seen. eral parathyroid adenoma.
Conclusion: Osteolytic lesions of hyperparathyroidism are rare and his-
tologically indistinguishable from GCT, which can be misdiagnosed. The
E-PS-23-014 gold standard for definitive diagnosis is multidisciplinary: radiographic,
Malign Ossifying Fibromyxoid tumour of axilla; a rare case clinical presentation and biochemical testing. Treatment of GCRG con-
S.Y. Celik1, O. Ilhan Celik1, Y. Dere1, O. Dere2 sists mostly of parathyroidectomy.
1
Mugla Sitki Kocman University, Faculty of Medicine, Department of
Pathology, Turkey, 2 Mugla Sitki Kocman University, Faculty of
Medicine, Department of Surgery, Turkey E-PS-23-016
Sporadic giant diffuse neurofibroma in a 40-year-old patient. Case
Background & Objectives: Ossifying fibromyxoid tumour(OFMT) is report and literature review
rare soft tissue tumour of uncertain origin. It generally occurs skel- O.C. Voinea1, A. Dumitru2,3,4, C. Savlovschi2,3, T.A. Georgescu2,3, C.
etal muscle of the extremities or subcutaneous tissues and less com- Secara1, M. Sajin2,3,4
1
monly in head, neck, trunk, mediastinum or retroperitoneal region. CCSMM, Romania, 2 SUUB, Romania, 3 UMF Carol Davila,
Although majority of them behave like a benign tumour, very rare Bucharest, Romania, 4 European Society of Pathology, Romania
cases including cellular atypia, elevated mitotic activity and infiltra-
tive behaviour proceed very aggressive and are called Atypical or Background & Objectives: Gigantic neurofibroma is an extremely rare
Malign OFMT. tumour, with a challenging surgery management and pathologic differen-
Methods: A 20-year-old male was admitted to surgery clinic be- tial diagnostic, more often seen in neurofibromatosis syndromes, excep-
cause of a soft, fixed, rapidly growing mass in his right axillary tionally rare in a sporadic form.
region. The ultrasound revealed an infitrative, solid-heterogeneous, Methods: A 40-year-old male with no significant medical history pre-
6cm mass containing cystic and calcified areas. sented in the surgery department with a gigantic tumour localized on the
Results: Total excision of the mass was performed and in the forearm for a wide local excision. His only complains were aesthetic and
histopathological examination the hypercellular lesion was com- functional because of the difficulties in getting his armed dressed. After
posed of ovoid/round, pleomorphic, mitotic active(4/10HPF) cells imagistic evaluation, surgical excision was performed, and the resected
composing nodular, trabecular, cord-like areas in a fibromyxoid specimen was entirely submitted for pathological examination in the
matrix rich in vessels. Also dense collagenous and ossifying areas Department of Pathology of the University Emergency Hospital of
were present in the lesion. The tumour cells, expressing Vimentin Bucharest.
and s100 were infiltrating the surrounding adipous tissues. As a Results: The gross examination revealed a 14/10/8 cm nodular
result the lesion was diagnosed as Malign OFMT. tumour. The histopathological examination revealed a monomor-
Conclusion: OFMT was firstly described as a benign tumour with low phic proliferation of small to medium-size spindle cells, with
risk of recurrence; however later it was seen that as this tumour contained wavy hyper-chromatic nuclei organized in poorly formed fasci-
more mitosis, cellularity and atypia the recurrence rates elevated, even cles. No capsule was identified, and the profound margins extend-
metastasis were seen in the most atypical cases. So it was classified as ed to the deep hypodermic layer, in the vicinity of a muscular
typical, atypical and malignant OFMT. Cases showing high nuclear fascia. The proliferation entrapped eccrine glands and piloseba-
grade, high cellulrity and mitotic activity>2/50HPF were named as ma- ceous units. No mitotic figures, necrosis or hemorrhage were ob-
lign OFMT like our case. served. The diagnosis of giant diffuse neurofibroma was con-
firmed by additional ancillary tests: the cells were 100% positive
for S100, negative for CD34 and SMA and only about 3% were
E-PS-23-015 positive for Ki67.
Giant cell reparative granuloma as clinical presentations of a second- Conclusion: The particularity of this case is underlined not only
ary hyperparathyroidism: awareness is necessary by the rarity of this tumour type and the multidisciplinary man-
F. Ramalhosa1, C. Faria1, R.C. Oliveira1, M.J. Martins1, M.A. Cipriano1 agement required, but also by the differential diagnostic with
1
Centro Hospitalar e Universitário de Coimbra, Portugal MPNST, fibrosarcoma or other malignant tumours, considering
the localization and also the apparently invasive behaviour.
Background & Objectives: Giant Cell Reparative Granuloma (GCRG)
is a reactive intraosseous proliferation, characterised as a well-defined
lytic lesion that may involve any portion of the bone. However, GCRG E-PS-23-017
shares histologic features with conventional Giant Cell Tumour (GCT). Biphasic synovial sarcoma mimicking Morton neuroma- a case
GCT has a benign behaviour with high local aggressiveness, rarely report
Virchows Arch

L. Tomescu1, V. Enache2, I. Salem3, F. Andrei3, C. Girbea3, A. Curte3 Neoplastic stromal cells persisted only in small areas of the tu-
1
University Emergency Hospital, Bucharest, Romania, 2 Victor Babes mour, fact confirmed by the decreased positivity of p63 on the
National Institute of Pathology, Romania, 3 Elias University Emergency resection specimen compared to the biopsy and the decrease of
Hospital, Romania the proliferation index Ki67 from 15%, to <2% after therapy.
CD34+ in vessels and SMA+ in stroma.
Background & Objectives: Synovial sarcoma (SS) is a rare malignant Conclusion: Neoadjuvant therapy with Denosumab considerably re-
mesenchymal neoplasm, associated with chromosomal translocations in- duced the number of mononuclear neoplastic cells, osteoclast-type cells,
volving genes like SS18 and SSX1, SSX2 or SSX4 and it accounts for 5- the proliferation index Ki67 and tumour size, producing reactive ossifi-
10% of all soft tissue sarcomas. SS affects young adults with a median cation which altogether favoured complete and safe resection of the tu-
age of 35, predominantly males and involves mainly the extremities mour.
(68,7%). Morphology includes monophasic, biphasic and poorly differ-
entiated patterns.
Methods: This report describes a case of a 51-year-old female who pre- E-PS-23-019
sented for painful subcutaneous tumour located in the third interdigital A case series of 3 primitive myxoid mesenchimal tumour of infancy,
space of the right lower limb having MRI characteristics suggestive of including one case with brain metastasis; histopathologic, immuno-
Morton neuroma. After surgery, the specimen was processed and examined histochemical and molecular investigation
by standard H&E technique, PAS, Giemsa, and immunohistochemistry. î Kutlu1, H.K. Türköz2, T. Celkan3, S. Çınar özel3, N. Çomunoğlu1
1
Results: Gross examination identified a well circumscribed, partially Istanbul University Cerrahpasa-Cerrahpasa Medical Faculty
encapsulated, firm, subcutaneous mass, measuring 1.5 cm in maximum Department of Pathology, Turkey, 2 Marmara University, Turkey,
3
diameter. Microscopically, the tumour showed a biphasic proliferation Istanbul University Cerrahpaşa Medical Faculty Paediatric Oncology
consisting of spindle cells with mild to moderate nuclear pleomorphism Department, Turkey
and gland-like epithelial structures containing mucus and abundant
intermixed mast cells, which were positive on Giemsa stain. The tumoral Background & Objectives: Primitive myxoid mesenchymal tumour
stroma showed hemangiopericytomatous vessels with focal thrombosis of infancy (PMMTI) is a distinct, relatively rare soft tissue tu-
and microhemorrhagic areas, hemosiderin deposition, and frequent calci- mour characterised by proliferation of immature mesenchymal
fications. The histological aspects were suggestive of synovial sarcoma. cells, diffuse myxoid background with delicate vascularity on his-
The diagnosis was confirmed by immunohistochemistry: the spindle cell topathology. To this date, 31 cases had been reported in literature
component was positive for S100, CD99 and CD56 and negative for in total. It is known to have a relatively good clinical course with
desmin and CD34, and the gland-like structures were positive for CK7. mainly local recurrences, although one case with differentiation to
The tumour was incompletely excised. undifferentiated sarcoma and one case with brain metastasis was
Conclusion: The particularity of this case is the misleading clinical pre- reported. In this study we present 3 PMMTI cases, one with brain
sentation resembling Morton neuroma, the small dimension, and abun- metastasis
dant mast cells and microcalcifications. Methods: 3 PMMTI cases detected in Istanbul University,
Cerrahpaşa-Cerrahpaşa Medical Faculty between 2015 and 2018
were presented. The histopathologic properties of the cases were
E-PS-23-018 compared as they were seen in light microscopy. An immunohis-
Neoplastic stromal cell persistence in a case of giant cell tumour of tochemical work up panel made up of desmin, CD99,myo-D1,
bone successfully treated with Denosumab before surgery - immuno- S100,Bcl6,CyclinD1 were used. ESWR-1 rearrengement, N-myc
histochemical analysis rearrengement, DDIT-3 translocation and ETV6–NTRK3 gene fu-
D. Costache1, D.M. Pop2 sion was investigated with FISH.
1
Pathology Department, Colentina University Clinical Hospital, Results: Ages of the babies when they presented with tumour were 18
Bucharest, Romania, 2 "Foișor" Clinical Orthopaedics and weeks, 5 months and 7 months respectively. Female/male ratio was
Traumatology Hospital, Bucharest, Romania 1/2.Histopathologic investigation showed a tumour made up of primitive
Background & Objectives: Giant cell tumour of bone (GCTB) is a small tumour cells with myxoid background. Immunhistochemical work
benign, locally aggressive, primary bone tumour composed of up stained positive for Bcl-6 and cyclin D1 in all cases. ESWR-1
mononuclear neoplastic stromal cells which express receptor activa- rearrengement, N-myc rearrengement,DDIT3 translocation ETV6–
tor for NF-κβ ligand(RANKL), admixed with mononuclear NTRK3 gene fusion were negative with FISH. One case presented with
macrophage-like osteoclast precursors and osteoclast-type giant brain metastasis during follow up and died 18 months after diagnosis.
cells, which both express RANK. Denosumab is a monoclonal an- Conclusion: PMMTI is a rare infanil tumour, often with local aggressive
tibody that binds to RANKL, thus preventing osteoclastic activa- behaviour. Metastasis is not a common finding. In recent years BCOR
tion. The purpose of this study is to evaluate the impact of tandem duplication was defined to be positive in PMMTI cases, a prop-
Denosumab in GCTB and to provide histopathological and immu- erty shared with some of the soft tissue undifferentiated round cell sarco-
nohistochemical proof of the benefits of this treatment. mas, suggesting a possible grey zone between those two entities. In this
Methods: We present a case of GCTB, of distal ulna, in a 65- study we share our experience with 3 PMMTI cases, 1 with brain metas-
year-old, female, diagnosed in “Foișor” Clinical Hospital, in 2018. tasis and aggressive behaviour.
Clinical and imaging assessment was performed. Histopathologic
diagnosis of GCTB was established by tumour biopsy. Due to the
size and soft tissue extension of the tumour the patient received E-PS-23-020
Denosumab therapy before surgery for resection of the distal ulna Giant myelolipoma of adrenal gland - presentation of two cases with
and reconstruction. H&E and p63, CD56, CD34, SMA, Ki67 im- review of the literature
munohistochemical markers were performed for both the biopsy A. Szumera-Cieckiewicz1, O. Kuczkiewicz-Siemion2, P. Rutkowski3, T.
and the resection specimen. Goryn3, M. Zdzienicki3, M. Prochorec-Sobieszek2
1
Results: After Denosumab the tumour had better-defined margins, Institute of Haematology and Transfusion Medicine, Diagnostic
decreased in size and showed increased reactive bone formation Haematology Department, Poland, 2 Maria Sklodowska-Curie Institute
with numerous CD56+ osteoblasts. Few osteoclast-type cells - Oncology Center, Department of Pathology and Laboratory Medicine,
remained and they were smaller and had fewer nuclei. Poland, 3 Maria Sklodowska-Curie Institute - Oncology Center,
 Virchows Arch

Department of Soft Tissue/Bone Sarcoma and Melanoma, Poland Results: The microscopic image of lymph nodes and iliac tumour
showed solid fields of macrophages and histiocytes with focal
Background & Objectives: Adrenal myelolipoma (AML) classi- necrosis accompanied by the giant multinucleated cells with aster-
fied according to the latest update of the World Health oid bodies and birefringent foreign particles (polyethylene). The
Organization on endocrine tumours as a benign mesenchymal and metastases were excluded and the final diagnosis of metal-related
stromal neoplasm which is composed of mature fat and trilinear sinus histiocytosis and dendritic pseudotumor were identified
myeloid tissue. AML after adrenocortical adenoma is the second respectively.
most common primary adrenal incidentaloma. Tumours exceeding Conclusion: Lymphadenopathy or tumour mass after joint replace-
10 cm in diameter are called giant myelolipomas. Although it has ment rarely is a reactive reaction to implant material. In the his-
benign behaviour the clinical and radiological diagnosis might be topathological assessment, immunohistochemical panel both with
difficult or confusing since AML might mimic the malignant polarizing light evaluation is useful in establishing the diagnosis
neoplasm.
Methods: We present two cases of males a 78 and a 64-year old
who were admitted to Maria Sklodowska-Curie Institute-Oncology E-PS-23-023
Center, Warsaw, Poland with suspicious adrenal gland tumours. A case of cutaneous Ewing sarcoma in a young female with a history
Both patients after radiological evaluation underwent surgical ex- of acute myeloid leukaemia
cision of tumours. C. Masaoutis1, I. Themeli2, F. Dolkiras1, V. Pantelaion1, E. Dimitriadis3,
Results: Macroscopically, the first was encapsulated with dimen- D. Rontogianni1
1
sions 19x13x12 cm; the second one was characterised by lack of Evaggelismos General Hospital of Athens, Greece, 2 Hygeia Hospital,
capsule and dimensions 14x13x5.5 cm. Microscopically, tumours Greece, 3 Aghios Savvas General Oncology Hospital, Greece
were a mixture of a dense adipose tissue with hematopoietic tissue
including abundant mature erythroid and granulocytic elements as Background & Objectives: A 17-year old girl with a history of
well as megakaryocytes. The immunohistochemical panel confirmed acute myeloid leukaemia 3 years ago presented with a 1.2cm
tri linea r hem atopoiet ic differe nti ati on. F urt herm ore, the cutaneous nodule of the interdigital space of the left foot. No
extramedullary hematopoiesis caused by chronic hematopoietic dis- osseous lesion is appreciated. Excisional biopsy was performed.
orders and endocrine disorders were excluded. Methods: Light microscopy, immunohistochemistry, reverse transcrip-
Conclusion: The variable proportion of fat and hematopoietic ele- tion polymerase chain reaction (RT-PCR) and fluorescent in situ hybrid-
ments and, the absence of the tumour capsule may direct the ization (FISH).
differential diagnosis of AML to adrenocortical cancer. Detailed Results: The dermis is involved by a uniform medium-sized cell
imaging including computed tomography and magnetic resonance population with scant cytoplasm, stippled chromatin, brisk mitotic
imaging might be helpful. The giant AML even asymptomatic activity and a lobular pattern with occasional cystic spaces.
usually requires surgical intervention which typically resolves as- Immunohistochemistral findings: Expression of vimentin, CD99, and,
sociated endocrine disorders; the histopathological examination is focally, FLI1 and desmin, without immunoreaction for haematolymphoid
the ultimate method in AML recognition. or neuroendocrine markers, cytokeratin or neurofilaments. Retained ex-
pression of INI1. RT-PCR revealed EWS/FLI chimeric transcripts due to
a t(11:22)(q24:q12) translocation. FISH with break-apart probes revealed
E-PS-23-021 rearrangement of the EWSR1 gene.
Metal-related histiocytosis of lymph node and dendritic pseudotu- Conclusion: These findings are diagnostic of Ewing sarcoma (ES).
mour of iliac bone - a spectrum of the same entity - two cases of Development of leukaemia has been reported following treatment
metallosis after arthroplasties of cutaneous ES, but not preceding it. Its distinction from
A. Szumera-Cieckiewicz1, K. Sokol1,2, M. Wagrodzki2, T. Goryn3, B. haematolymphoid malignancies (myeloid sarcoma or lymphoblas-
Szostakowski2, A. Pienkowski2, M. Prochorec-Sobieszek2 tic lymphoma) is crucial due to morphological overlap and CD99
1
Institute of Haematology and Transfusion Medicine, Diagnostic or FLI1 expression. Cutaneous presentation of ES is very unusual
Haematology Department, Poland, 2 Maria Sklodowska-Curie Institute (<3% of soft tissue ES), has a wide anatomical distribution, fe-
- Oncology Center, Department of Pathology and Laboratory Medicine, male preponderance, a predilection for children, adolescents and
Poland young adults, and a rather favourable prognosis (10-year survival
rate >90%).
Background & Objectives: Metallosis is an arthroplasty complica-
tion consisting of periprosthetic soft tissue and bone infiltration
by metallic particles and may be associated with significant E-PS-23-024
osteolysis around the implant. It has been described after total Retroperitoneal myelolipoma: a case report
hip, knee, and shoulder arthroplasties with prostheses containing E. Ben Hadj Khalifa1, A. Baccouche1, S. Ben Khlifa1, D. Chiba1, O.
titanium, cobalt, and chromium. The most frequent localized ad- belKacem3, H. Salifou1, B. Sriha1
1
verse reactions to metal debris include aseptic lymphocytic vascu- Pathology Department, Farhat Hached Hospital, Sousse, Tunisia
litis, diffuse chronic synovitis, and well-defined granulomas; the
lymph node involvement is exceptionally reported. Background & Objectives: Myelolipomas are rare, benign tumours
Methods: The first case was a 43-year-old man with a left inguinal mass, which occur usually in the adrenal glands and are composed of
which in ultrasound examination showed were described as metastatically mature adipose tissue and benign hematopoietic cells. Extra-
suspected enlarged lymph nodes. The patient underwent removal of the adrenal myelolipomas are rarer. This entity should be recognized
distal femur with prosthetic replacement due to high-grade osteosarcoma as it can reach a significant size and be responsible of pressure
twenty years ago with soft tissue relapse after four years. symptoms and it is often mistaken for malignant tumours. We pres-
The second case was 72-yeard old female administered with a ent a myelolipoma case in the retroperitoneal region. In this obser-
pelvic tumour. The patient underwent right hip replacement eight vation we will illustrate the clinical, radiological and pathological
years earlier because of arthropathy. Computed tomography aspects of myelolipoma.
showed an osteolytic tumour in iliac bone with damage of bone Methods: We report the case of a 63-year-old woman presenting for low
and soft tissue. Radiologically the metastases were considered. back pain that has been evolving for few months. The clinical and
Virchows Arch

1
complementary examinations concluded to a tumoral process of the ret- Pathology Department, Biomedical Diagnostic Center (CDB), Hospital
roperitoneal region suggestive of liposarcoma. Clinic of Barcelona, Spain, 2 Gastrointestinal Surgery Department, Clinic
Results: The patient had a complete resection of the tumour and Institute of Digestive and Metabolic Diseases (ICMDiM), Hospital Clinic
biopsy samples of the adrenal gland. The macroscopic examination of Barcelona, Spain,
concerned a well-circumscribed and encapsulated mass, measuring
10 * 9 * 4 cm and weighing 260 g. It has a gray color and show Background & Objectives: Lynch syndrome (LS) patients have a high
numerous foci of hemorrhagic reshuffle and yellow foci of adipose risk of developing various tumours specially colorectal and endometrial
appearance. cancers. We report the first case of TFE3-rearrangement-associated
The microscopic examination revealed that this mass is done by two PEComa described in a LS patient.
contingents: a mature adipose tissue and a hematopoietic tissue rich in Methods: A 2,5 cm pelvic nodule was detected on a follow-up MRI of a
myeloid, erythroid, and megakaryocytic elements. The tumour is largely 38-year-old male with LS and previous history of mucinous adenocarci-
remodeled by hemorrhage and fibrinoid necrosis. It includes a 3mm os- noma of the rectum. Surgical exeresis with clinical suspicion of metastatic
sification focus. adenopathy was performed.
The adrenal biopsy showed a normal adrenal cortex without any tumour. Results: Histologically, the lesion was constituted of nests of neo-
Conclusion: Myelolipoma is an invariably benign tumour. Its diagnosis plastic epithelioid cells with abundant clear cytoplasm and round or
must be raised if the tumour has a slow-growing and a mixed radiologic oval nuclei with small nucleoli separated by delicate fibrovascular
nature. Small and asymptomatic myelolipomas need clinical and radio- septa, with presence of hemosiderin and melanin pigments.
logic monitoring, while large and symptomatic myelolipomas should Occasional nuclear pleomorphism without necrosis or mitotic activ-
incur resection. ity was noted. Neoplastic cells were positive for HMB-45 and
TFE3. Scattered cells were positive for MelanA and actin, whereas
cytokeratins, S-100, desmin, PAX-8, and RCC were negative.
E-PS-23-025 Nuclear expression of MLH1, MSH2, MSH6 and PMS2 proteins
Adrenal lipomatous ganglioneuroma: a case report was preserved. TFE3 gene rearrangement was confirmed by FISH.
M. Oliveira1, L. Brochado Ferreira2, C. Estima Fleming2, R. Amorim3, B. Pathological diagnosis was PEComa with TFE3 rearrangement.
Fernandes2, N. Jorge Lamas1, J.R. Brandao2, J.R. Vizcaino1 Only 41 TFE3-rearranged PEComas have been reported in the liter-
1
Anatomical Pathology Service, Department of Pathology, Hospital and ature; 8 (19%) had an aggressive behavior. Our patient has no tu-
University Center of Porto, Porto, Portugal, 2 Centro Hospitalar e mour recurrence 10 months after surgery.
Universitario do Porto, Portugal Conclusion: To our knowledge neither classic PEComas nor TFE3-
rearranged PEComas have been described before in LS patients. Based
Background & Objectives: Ganglioneuroma is a rare, benign tumour on this fact and on its mismatch repair proteins proficiency, we consider it
that arise from neural crest cells of sympathetic ganglia or adrenal me- as a rare sporadic LS-unrelated tumour.
dulla. Lipomatous ganglioneuroma is an uncommon variant,
characterised by a conventional ganglioneuroma admixed with a mature
adipocytic component. The present case documents an adrenal E-PS-23-027
ganglioneuroma with an adipocytic component. Sporadic epithelioid sarcoma, proximal type, in a woman with Muir-
Methods: An incidental adrenal mass was identified in an asymp- Torre Syndrome type one
tomatic 46-year-old male. Radiological examination suggested that A. Abuomar1
1
the mass had unspecific characteristics. His physical examination Hospital General Universitario de Elda, Alicante, Spain
was unremarkable. Routine laboratory test results were within nor-
mal limits. He underwent right adrenalectomy, the specimen was Background & Objectives: Muir–Torre syndrome (MTS) is a rare he-
routinely processed, sections were stained with hematoxylin-eosin reditary autosomal dominant syndrome, a variant of Lynch syndrome,
and immunostains were performed. characterised by sebaceous neoplasia or keratoacanthomas associated
Results: Grossly, the tumour was well circumscribed but not encap- with visceral malignancies. Sarcomas are rarely associated with MTS.
sulated, it had a whitish cut surface and rubbery consistency. It was Up to our knowledge this the first case in the literature with epithelioid
adhered to the right adrenal gland, causing an expansive effect. sarcoma associated with Muir -Torre syndrome.
Microscopically, the tumour was predominantly composed of ma- Methods: 80 years old woman with medical history of MTS type one:
ture ganglion cells scattered in a background of Schwann cells ar- endometrial adenocarcinoma, colorectal adenocarcinoma, multiple seba-
ranged in small intersecting fascicles. Intermixed clusters of non- ceous and squamous cell carcinoma of the skin with a loss of expression
atypical mature adipocytes were found. Cellular atypia, mitoses and of MLH1 and PMS2. During the last follow-up CT scan evaluation a
necrosis were absent. The tumour had clear association with adrenal diffuse enlargement of left iliacus muscle was seen, suggesting hemato-
cortex. By immunohistochemistry, both ganglion cells and Schwann ma. Core needle biopsy of the lesion was performed.
cells were positive for S100 protein, neurofilament protein and synaptophysin, Results: The tumour was composed of sheets of atypical large round or
whereas ganglion cells were also positive for chromogranin. polygonal epithelioid cells mixed with spindled cells. Neoplastic cells showed
Conclusion: To the best of our knowledge, this is the second report an abundant ill-defined eosinophilic cytoplasm, pleomorphic hyperchromatic
of a lipomatous ganglioneuroma in adrenal gland. Ganglioneuroma nuclei with open chromatin, irregular nuclear membrane and prominent nu-
with adipocytic component should be considered in the differential cleoli. Frequent mitosis were seen. Immunohistochemical (IHQ) stains
diagnosis of fat-containing adrenal and retroperitoneal masses, and showed:CK7+,Vimentin +,S M Actin+, Caldesmon+,MLH1+,PMS2+
more cases of this entity should be studied in order to understand ,MSH2+,MSH6+,CKAE 1-3-,CK20-,CDX2-,TTF1-.Desmin-,
this phenomenon. CD34-,CD31-,CD117-,P63,EMA-, HMB45- S100-,Uroplakin3-,
Sinaptoficina-,Calretinin-. KI67>80%. Morphology and IHC findings were
consistent with a mixed type proximal type Epithelioid sarcoma
E-PS-23-026 Conclusion: Epithelioid sarcoma is a rare, high-grade, malignant soft
TFE3-rearranged PEComa in a Lynch syndrome patient, with liter- tissue tumour with unknown histogenesis, characterised by epithelioid
ature review and/or spindled cells morphology. It accounts for less than 1% of all soft
A.B. Larquè1, G. Frigola1, S. Díaz-Mercedes1, N. Castrejón1, A.M. tissue sarcomas. It´s association with Lynch Syndrome is extremely rare,
Lacy2, A. Castells2, M. Cuatrecasas1 if existed. Diagnosis is based on clinical, morphological, IHC and
 Virchows Arch

molecular study. The differential diagnosis should be made mainly with integumentary tumour showed a diffuse fascicular spindle cell prolifera-
granulomatous inflammatory process, undifferentiated carcinoma, tion infiltrating dermis and numerous blood filled spaces between the
amelanotic melanoma, rhabdomyosarcoma and synovial sarcoma. spindle cell component. Moreover, spindle endothelial cells aggregates
and dilated vascular channels containing erithocytes were noticed on
spleen parenchyma and oesophageal mucosa and submucosa. The tumour
E-PS-23-028 stroma showed intermixed abundant plasma cells, associated with
An extra-osseous Ewing sarcoma after successful treatment of pri- microhemorrhagies and hemosiderin deposition. The histological aspects
mary osteosarcoma: an unexpected pathological finding were suggestive of disseminated KS. The vessels stained positive focally
M. Mellouli1, O. Boudawara1, C. Chaari1, A. Sallemi2, R. Kallel1, T. to CD34, isolated to vimentin and negative to SMA. Gomori stain
Sallemi Boudawara1, H. Mnif1 showed a liniar continuous network of capillaries with a nodular pattern.
1
Department of Pathology, Habib Bourguiba Hospital, Sfax, Tunisia, Conclusion: The particularity of this case is the disseminated form of KS
2
Department of Radiology, Habib Bourguiba Hospital, Sfax, Tunisia at an intravenous drug-addict patient with HIV/AIDS.

Background & Objectives: Since the introduction of chemotherapy as a

therapeutic standard in osteosarcomas, the risk of secondary-malignant- E-PS-23-030
neoplasms (SMN) has increased. Soft-tissues sarcomas have been rarely Langerhans cell histiocytosis of bone with BRAF V600E mutation: a
reported as SMN in survivors. This report tries to illustrate secondary case report and the review of published work
Ewing sarcomas’characteristics. N. Kaya Terzi1, I. Yilmaz2
1
Methods: We present the case of a boy who developed an extra-osseous University of Health Sciences, Sultan Abdulhamid Han Training
Ewing sarcoma in his right thigh 5 years after treatment of a primary Hospital, Istanbul, Turkey, 2 Ministry of Health, Provincial Health
osteosarcoma. Directorate Istanbul, Sultan Abdulhamid Han Sample Training and
Results: A 13-year-old-boy was diagnosed with a non-metastatic osteo- Research Hospital, Department of Pathology, Turkey
sarcoma of the left femur. He had a history of a myxoidchondrosarcoma
of the scapula in his grandfather. The patient received preoperative che- Background & Objectives: Histiocytoses, including Langerhans cell
motherapy (methotrexate, etoposide, ifosfamide) followed by a tumour histiocytosis (LCH) are rare disorders characterised by the proliferation
resection. Pathological examination of the resection specimen concluded of cells derived from monocyte/macrophage lineages. The etiology of
to a poor response to chemotherapy (amount of induced-tumour-necrosis these diseases remains unclear. However, oncogenic BRAFV 600E muta-
didn’t outreach 82%). Thus, the patient underwent an intensified post- tions have been identified in LCH.
operative chemotherapy (adriamycin, cisplatinum). Five years after, he Methods: Here, we report the case of a 26-year-old man with a 3-month
developed a 2cm-right-thigh-swelling. Soft-tissues-ultrasound-imaging history of left acetabulum posterior mass. No abnormality was detected in
revealed a 2cm-hyper-vascular mass suggesting a subcutaneous metasta- his other organs, and incisional curettage of the mass was performed.
sis of his osteosarcoma. Surprisingly, pathological findings of the resec- Routine pathological examination was performed. After immunohisto-
tion specimen evidenced sheets of monomorphic-small-round-cells with chemical examination Sanger sequencing PCR was used to detect
some pseudo-rosettes. Immuno-histochemical staining showed CD99- BRAF-V600E mutation in paraffin-embedded tissue samples.
strong-cytoplasmic-membrane positivity. NSE was weakly positive while Results: In pathological examination; among the bone trabeculae,
chromogranin, synaptophysin, PS100, LCA and pan-cytokeratin were Langerhans cells with a diameter of 12 - 15 microns were observed with
negative. A secondary extra-osseous-Ewing-sarcoma was then irregular and long-core, fine chromatin and indeterminate nucleoles, with
diagnosed. abundant, pale eosinophilic cytoplasm, prominent nuclear grooves and
Conclusion: We report the first case in literature of secondary extra- folds. Eosinophils were observed in groups between these cells.
osseous-Ewing-sarcoma after successful treatment of osteosarcoma. Histopathological examination revealed the coexistence of LCH.
Immunohistochemistry showed that most of the large histiocytes were
positive for CD68, S100, and CD1a, supporting the diagnosis of LCH.
E-PS-23-029 In addition, these cells were positive for BRAFV 600E mutation. BRAF
Disseminated form of epidemic HIV/AIDS-associated Kaposi inhibitors were given for medical therapy.
Sarcoma in a young male - a case report Conclusion: Children with LCH tend to have a high OS rate and a high
L. Tomescu1, A. Tita2, L. Luca2, M. Bosa2, D. Enea1, M. Ceausu2 incidence rate of BRAF-V600E mutation. The positive rate of BRAF-
1
University Emergency Hospital, Bucharest, Romania, 2 "Mina V600E gene mutation is not associated with age, sex, affected organ,
Minovici" National Institute of Legal Medicine, Bucharest, Romania clinical classification, early treatment response, recurrence, and 2-year
OS of the children with LCH, but it is associated with clinical grouping
Background & Objectives: K ap o s i Sa rc o ma ( KS ) is an of LCH. On the otherside some of the researches show that ,in children
angioproliferative malignant tumour caused by human herpesvirus with LCH, BRAF(V600E) mutation was associated with high-risk fea-
8 infection. The epidemiological classification of KS includes four tures, permanent injury, and poor short-term response to chemotherapy.
subtypes, such as: classic KS in elder men of Mediterranean origin, So we should follow up this patient carefully.
endemic KS in younger African men, iatrogenic KS due to immu-
nosuppressive therapies and epidemic HIV/AIDS- associated KS.
Today, KS is the most common neoplasm of people with HIV/ E-PS-23-031
AIDS. Cell composition in the bone giant cell tumour
Methods: We present the case of a 26-year-old deceased man known as V. Zakharava1, M.T. Mohammadi1,2, L. Pashkevich2, I. Shpileuski2
1
intravenous drug-addict, with a medical history of HIV/AIDS, Kaposi Belarusian State Medical University, Belarus, 2 Belarus Republic
Sarcoma, HCV hepatitis and bronhopneumonia. Unfortunately, he died Scientific and Practical Center for Traumatology and Orthopaedics,
due to systemic complications caused by multiorgan failure. Specimen Belarus
samples taken from lung, liver, kidney, oesophagus, spleen and skin were
processed and examined with standard H&E technique, Van Gieson and Background & Objectives: Giant cell tumour (GCT) of bone consists of 3
Gomori stains and immunohistochemistry. different cellular types: stromal fibroblast-like cells, mononucleated-
Results: The forensic autopsy revealed multiple reddish tumours local- macrophage cells and multinucleated giant cells. Only stromal fibroblast-
ized on the skin, oesophagus and spleen. Microscopically, the like cells are truly tumour cells in the heterogeneous cell mass of GCT.
Virchows Arch

Methods: We used immunohistochemistry (IHC) for differential diagno- Results: There are some basic points in this case that, at least initially,
sis of various forms of giant cell tumour (GCT) and identification of cell could mislead the diagnosis. The basic diagnostic problem was the total
specificity in GCT. absence of an atypical lipomatous tumour component. This is probably
Results: Given the GCT morphogenesis, consisting of 3 cell elements, due to an extensive dedifferentiation. Moreover, the dedifferentiated com-
we used various antibodies that detect common mesenchymal, osteoblas- ponent, generally represents a high grade sarcoma. In the remaining cases
tic, endothelial, B- and T-cells, and monocytic-macrophage cells. in which that component is of low grade, it usually resembles
Vemintin showed an immunopositive reaction in almost all tumour cells. “fibromatosis” or it shows a whorling “meningothelial” pattern. The sub-
CD68 shows immunopositive coloration with macrophages and giant cutaneous location is also extremely rare. And finally, from the clinical
cells. In this case, uneven jagged cytoplasmic membranes of giant multi- aspect, the tumour was very slowly growing which is not usually com-
nucleated cells are noted, which indicates similarity with osteoclasts. patible with a sarcoma.
Proliferative activity of stromal tumour cells with Ki-67 showed more Conclusion: Dedifferentiated liposarcoma is a tumour that shows a sig-
intense nuclear staining in malignant cases of GCT as compared to benign nificant histological heterogeneity, with multiple patterns of differentia-
GCT. In the tumour, foci with increased proliferative activity of tumour tion. Thorough sampling is needed to detect the atypical lipomatous com-
cells are determined - "hotspots". We also observed that in the GCT with ponent which is very helpful to the final diagnosis.
infiltrating growth in the "invasive fronts" of the tumour, i.e. in areas of
the tumour with an extra-bone extension into the periosteum or the sur-
rounding soft tissue, tumour cells have more pronounced pro-liferative E-PS-23-033
activity. IHC studies with CD5, CD20 and CD79a, CD45 and CD138 Pleomorphic lipomas: case series
showed a weak immune response. The distribution of lymphocyte cells in S. Demir1, A. Avci1
1
the tumour is uneven. Izmir Katip Celebi University, Ataturk Training and Research Hospital,
Conclusion: GCT has high osteoblastic and osteoclastic activity. The Department of Pathology, Turkey
processes of osteogenesis and osteolysis synchronously and permanently
occur in the GCT. The quantification of osteoblasts with osteonectin, Background & Objectives: Pleomorphic lipomas are very rare, benign
together with proliferative activity index with Ki-67, can provide useful neoplasms resembles the usual type of lipoma, except for gray-white
information in the differential diagnosis between benign and malignant gelatinous foci, representing the areas of increased cellularity. They con-
forms of GCT. stitute in the subcutaneous tissue of the posterior neck, shoulder, and
back. Most of them between 3 and 5 cm and usually well circumscribed.
We aimed to review these cases we encounter in our daily practice.
E-PS-23-032 Methods: All the patients with pleomorphic lipomas who were operated
A dedifferentiated lipoarcoma of the buttock with unusual in our hospital between October 2006 and February 2019 were evaluated
presentation retrospectively. Demographic characteristics, size, location and other as-
G. Agrogiannis1, A. Terra2, S. Kykalos2, A. Lazaris1, G. Tsourouflis2 sociated lesions were recorded.
1
1st Department of Pathology, School of Medicine, National and Results: A total of 6 pleomorphic lipoma cases were detected.Three
Kapodistrian University of Athens, Greece, 2 2nd Department of ( % 50) of the cases were male and 3 (50%) were female. The mean
Propedeutic Surgery, School of Medicine, National and Kapodistrian age was 49 years (32-59). Two (%33) of the cases were localized
University of Athens, Greece right hand and the other locations were right leg (%16), left heel
(%16), neck (%16) and right-left conjunctiva (%16). The mean di-
Background & Objectives: A 52-year-old female patient presented to our ameter of the lesions was 3 cm (0.8-6). Macroscopically, most of the
clinic with a soft tissue growth on her right buttock which had been present lesions circumscribed,solitary and centered in the subcutaneous tis-
for the past 5 years. The mass had been slowly growing with a more sue. Histopathologically, lesions were predominantly composed of
prominent growth in size over the last 2 years. At the time of presentation, mature adipose tissue with scattered spindle cell or pleomorphic
the patient complained of atypical symptoms such as tenderness when elements in the majority of cases.
seated and right-sided lower back pain. Physical examination revealed a Conclusion: Pleomorphic lipomas are very rare lesions, often slowly
soft, nontender palpable right buttock mass, 4-5cm in diameter. After the growing, painless, arising mainly in men. Excision is basic treatment.
initial clinical evaluation, a soft tissue ultrasound and MRI of the pelvis was These lesions are a rare entity requiring differential diagnosis with many
obtained, and these demonstrated a heterogeneous subcutaneous mass subcutaneous tumours.
(64x23x46 mm) with no evidence of infiltration of the gluteus maximus.
One month after presentation, a complete surgical excisional biopsy with
clear margins was performed under local anesthesia. E-PS-23-034
Methods: Grossly, the surgical specimen was measuring 7.5x3.4x5 cm Gastrointestinal stromal tumour with dedifferentiation to
fully covered by adipose tissue. Upon sectioning, a circumscribed mass leiomyosarcoma
was revealed, about 6,5 cm in its largest diameter, with extensive cystic S. Bagbudar1, A.F.K. Gok2, K. Gunay2, I. Yilmaz3, M. Buyuk1, B.
appearance. Histological examination revealed a cytologically malignant Bilgic1, G. Unverengil1
1
neoplasm with multifocally prominent giant cells. The cells had round Istanbul Faculty of Medicine, Department of Pathology, Turkey,
2
and spindle morphology and the stroma was extensively hyalinized. In Istanbul Faculty of Medicine, Department of General Surgery, Turkey,
3
areas, the tumour cells were lining pseudovascular spaces, partly filled with Ministry of Health Istanbul, Provincial Health Directorate Istanbul,
erythrocytes. Mitotic figures were very rare and there wereno necrotic areas. Sultan Abdulhamid Han Sample Training and Research Hospital,
The tumour was well demarcated having a fibrous pseudocapsule and the Department of Pathology, Turkey
surrounding fatty tissue appeared normal. Immonohistochemistry initially
showed a focal positivity for S100, while AE1/AE3, CK19, EMA, CD30, Background & Objectives: Gastrointestinal stromal tumours (GISTs)
SMA, desmin, SOX10, CD34, CD31, ERG, TLE-1, were negative. Ki67 are the most common mesenchymal gastrointestinal tumours. Unlike
index was positive in 1-2% of the neoplastic cells. A secondary immuno- oth er sarcomas, dedifferen tiation is unu sual fo r GISTs .
histochemical staining was performed for MDM2 and CDK4 and these Dedifferentiated GIST without previous imatinib therapy is even
markers were positive in most of the neoplastic cells. The MDM2/CDK4 rarer, with few cases published to date. We describe an unusual case
genes amplification was confirmed by fluorescence in situ hybridization. of GIST with dedifferentiation to leiomyosarcoma without history of
Finally, the tumour was diagnosed as a dedifferentated liposarcoma, previous therapy.
 Virchows Arch

1
Methods: We report a case of 50-year-old male with an abdominal mass Marmara University Faculty of Medicine, Department of Pathology,
on greater gastric curvature, pathologic lymph nodes and colon implants Turkey
for three months.
Results: Gross examination revealed a tan-white, focally-necrotic and Background & Objectives: Perivascular epitheloid cell tumour
hemorrhagic 25 cm-mass of 2850 gr. Microscopic examination demon- (PEComa) is a rare mesenchymal tumour family composed of
strated two demarcated areas: a well-differentiated spindle cell compo- a n gi o my o l i p o ma , c l ea r ce l l ‘s u g a r ’ t u m o u r o f t h e l u n g,
nent and a pleomorphic component. Well-differentiated tumour com- lymphangiomyomatosis and a group of histologically and immunohisto-
posed of rather uniform, fusiform cells, with eosinophilic cytoplasm, chemically similar tumours arising in various soft tissue and visceral
arranged in intersecting fascicles or a short storiform pattern. organs. Clear cell myomelanocytic tumours of falciform ligamentum of
Pleomorphic tumour was composed of eosinophilic polygonal cells with teres is an extremely rare variant of PEComas.
bizarre nuclei, abundant cytoplasm, and increased mitotic activity with Methods: A 27- year –old woman presented with a 70x35x20 mm diam-
abundant tumour necrosis. On immunohistochemical studies, the well- eter mass lesion between duodenum and liver. It was found incidentally
differentiated component was positive for CD34, CD117 and DOG-1. Ki- during her pregnancy. She had idiopathic thrombocytopenic purpura dis-
67 proliferation index was 1%. Pleomorphic component stained positivite ease and no other remarkable symptoms. A tumour arising from falciform
for smooth muscle actin and kaldesmon. Ki-67 labelling index was 70%. ligamentum of teres was found and resected during surgery.
Both were negative for S-100 and desmin. No loss of succinate dehydro- Results: Grossly; size of the resection specimen was 12.5x9x4 cm . On
genase B expression was determined. A diagnosis of dedifferentiated the cut surface, a 8x4x3 cm tumour was detected. It was solid, yellow in
GIST with leiomyosarcomatous differentiation was rendered. Molecular color, had foci of hemorrhage and a thin fibrous capsule. Histological
studies did not show any activating mutations for KIT, platelet derived examination revealed epithelioid or spindle shaped tumour cells that
growth factor alpha and BRAF gene. had clear to eosinophilic cytoplasm, and organized in a fascicular pattern.
Conclusion: Dedifferentiated GIST should be considered in the differen- Tumour cells arranged around hyalinized arterioles and capillaries.
tial diagnosis of abdominal masses and adequate gross sampling should Immunohistochemical analysis showed that tumour cells were positive
be performed to reveal conventional and dedifferentiated components. for SMA, HMB45 and negative for Desmin, CK, EMA, CD34 and
CD117. We reported the case as PEComa with uncertain malignant po-
tential, according to proposed classification of PEComas because of its
E-PS-23-035 size.
Primary Rosai-Dorfman disease of bone; a case report Conclusion: Clear cell myomelanocytic tumours of falciform
A.N. Yildirim1, R.B. Girgin1, T. Zenginkinet1, B. Simsek1, K. Ozkan2 ligamentum of teres are very rare and usually benign tumours.
1
Istanbul Medeniyet University, Department of Pathology, Turkey, They must be distinguished from gastrointestinal stromal tumours,
2
Istanbul Medeniyet University, Department of Orthopedics and melanomas, and clear cell sarcomas. Our patient was treated with
Traumatology, Turkey a resection without any adjuvant therapy and no recurrence has
been detected in follow up.
Background & Objectives: Rosai-dorfman disease (RDD) is a rare,
benign condition that causes proliferation of histiocytes, a type of
white blood cells, within the lymph nodes and other organs of the E-PS-23-037
body such as the skin, bone, breast, respiratory airways, and central Cellular cannibalism in giant cell rich lesions: is it worth scanning?
nervous system. Osseous involvement without lymphadenopathy G. Gul1, O. Oz2, M. Sezak3, I. Tamsel4, D. Sabah5, B. Doganavsargil6
1
(primary disease of bone) is stil rare and has been reported in only Tepecik Training and Research Hospital, Department of Pathology,
a small number of patients. We present a case of primary osseous Izmir, Turkey, 2 Bergama Hospital, Department of Pathology, Turkey,
3
RDD which is a 2-year-old boy presenting with a solitary osseous Ege University Faculty of Medicine Department of Pathology, Turkey,
4
mass lesion in the talus. Ege University Faculty of Medicine Department of Radiodiagnostics,
Methods: We present the case of a 2-year-old boy who presented with a Turkey, 5 Ege University Faculty of Medicine Department of
pathological fracture. Computed tomography revealed a soft tissue mass Orthopedics, Turkey, 6 Ege University Faculty of Medicine,
which was observed in the 17x10 mm size that affected all part of the Department of Pathology, Izmir, Turkey
talus, leading to loss of continuity in the cortex.
Results: Histopathological evaluation of biopsy specimen showed Background & Objectives: Cellular cannibalism, a phenomenon in
consisted of a background of a variably cellular mixed inflammatory which a larger cell engulf a smaller one (lymphocyte, erythrocytes), has
infiltrate composed of plasma cells, lymphocytes, neutrophils, foamy been previously defined in several malignancies and in Giant cell tumour
macrophages, eosinophils, and numerous large histiocytes. of bone (GCT) as well.
Characteristically, the large histiocytes contained abundant eosinophilic Methods: We designed a pilot study to search for the presence of
cytoplasm and demonstrated conspicuous emperipolesis with intracyto- cannibalistic giant cells (CGC) in giant cell rich lesions (13 con-
plasmic lymphocytes, plasma cells, or neutrophils. Immunohistochemical secutive chondroblastoma (CB), 13 Giant cell tumour (GCT), 13
stains showed that the large histiocytes were strongly positive for s-100 Tenosynovial giant cell tumour (TSGCT) cases). Number of giant
and CD68, negative for CD1a. cells (GC) and CGC per 10 high power field (hpf) (x40 magni-
Conclusion: RDD is a rare, nonmalignant histiocytic disorder with un- fication; 0.54 mm radius; Olympus BX50 microscope) were re-
known etiology. RDD infrequently affects bone as a primary or secondary corded and correlated with nonparametric tests.
form of the disease. The differential diagnosis often includes osteomye- Results: CGC were observed in 100% of GCT, 84.6% of CB and 53.8%
litis and hematopoietic neoplasms. Diagnosis rests on the identification of of TSGCT (p=0.012, chi-square). Median number of CGCs/10hpf were
the characteristic large s-100 positive histiocytes that demonstrate prom- higher in GCT than in CB, and in TSGCT; 6±6.9 (range:1-23), 2±1.7
inent emperipolesis. (range: 0-5), 1±2.2 (range: 0-7), respectively (p=0,004; Kruskal-Wallis).
Overall GC density was highest in GCT, followed by CB and TSCGT
(p=0.000, Anova). Recurrence rate was 53.8% for GCT, 30.8% for
E-PS-23-036 TSGCT and 15.4% for CB. Among recurrent cases 7 GCT (100%), 1
Clear cell myomelanocytic tumour (CCMT) of the falciform CB, 2 TSGCTs had CGCs.
ligamentum of teres: a case report Conclusion: Canniballistic cells were more frequently observed in
T. Oğuzsoy1, H. Sahin Ozkan1, H.K. Turkoz1 GCT in keeping with literature while TSGCT presented with the
Virchows Arch

5
lowest number of GCs and CGSs. Despite lower number of cases Maria Sklodowska-Curie Institute - Oncology Center, Department of
in the present study, the correlation of CGCs with recurrence Soft Tissue/Bone Sarcoma and Melanoma, Poland
appears to be a promising area of interest for further research.
Background & Objectives: Fibrous dysplasia (FD) is a benign
fibro-osseous bone tumour accounting for 5%-10% of benign
E-PS-23-038 bone tumours that includes monostotic fibrous dysplasia (70%-
Symptomatic spinal epidural angiolipoma in a 32 year-old pregnant 80%), polyostotic fibrous dysplasia (20%-30%), McCune-
patient: a case report Albright (2%- 3%) and Mazabraud’s syndromes. In 40-90% of
A. Saidi1, B. Laabidi1, R. Hedhli2, F. Gargouri1, N. Mansouri1, A. FD somatic mutations in GNAS gene (encoding α subunit of
Bouziani1, I. Msakni1 stimulatory G-protein-coupled receptor (Gsα)), mostly missenses
1
Pathology Department, Military Hospital for Instruction of Tunis, at codons 201 or 227 are detected. The same GNAS mutations
Tunisia, 2 Tunis El Manar University, Medicine School of Tunis are also identified in majority (up to 60%) of intramuscular myx-
Military Hospital of Tunis, Department of Pathology, Tunisia omas, rare benign soft tissue musculoskeletal tumours. Thus, de-
termination of GNAS mutations status may allow reliable differ-
Background & Objectives: Spinal angiolipomas are uncommon be- entiation of FD and myxoma from their close histologic mimics-
nign tumours composed of mature fat cells and prominent abnor- low-grade osteosarcoma and myxofibrosarcoma respectively. The
mal capillary-type vascularity. They predominantly arise in the aim was to identify somatic GNAS mutations in selected fibro-
mid-thoracic posterior epidural space. Pregnancy and weight gain osseous/musculoskeletal tumours and to assess the utility of
are suggested to be predisposing factors. Angiolipomas are tradi- GNAS molecular analysis in FD and myxomas differential
tionally classified into non-infiltrating and infiltrating subtypes. diagnosis.
The latter infiltrates the adjacent tissues, most commonly bone. Methods: DNA was isolated form 64 FFPE sections of : 23 newly diag-
However, both subtypes have an excellent prognosis with a low nosed FD, 10 longer lasting FD lesions, 5 low grade osteosarcoma, 4
recurrence risk after surgical treatment and no malignant transfor- intramuscular myxomas, 7 myxofibrosarcoma, 14 myxoma and 1 undif-
mation potential. Clinical symptoms include back pain, leg weak- ferentiated myxoma/myxofibrosarcoma. Mutations p.Arg201 and
ness and lower limb numbness or parasthaesia. These signs usu- p.Gln227 in GNAS gene were verified by Sanger sequencing.
ally have a progressive course and are related to spinal cord and/ Results: Mutations p.Arg201His/Cys were found in 15/23 (65%) of new-
or nerve root compression, or infiltration of surrounding tissue. ly diagnosed FD and 7/18 (39%) myxomas. No mutation was detected in
The treatment consists of surgical removal of the tumour. other fibro-osseous lesions of bones and low-grade myxofibrosarcomas.
We report a case of a symptomatic spinal epidural angiolipoma discov- Conclusion: Molecular verification of GNAS mutation in DNA isolated
ered during pregnancy in a 32-year-old patient. from FFPE enables differential diagnosis in significant number of fibrous
Methods: In a case of a spinal epidural angiolipoma in a pregnant young dysplasia and myxomas from their close histologic mimics and, hence,
patient, the clinical and pathological parameters are studied and can be incorporated as an additional test for routine diagnostic procedure.
discussed.
Results: We report the case of a 32-year-old female presenting
with a progressively worsening paraparesis. Symptoms have ap- E-PS-23-040
peared during pregnancy. MRI performed in the postpartum period Giant cell tumour of the soft tissue presented as an unusual breast lesion
revealed a well circumscribed spindle shaped epidural mass ex- M. Ninkovic1, J. Sopta2, N. Lujic3, G. Đuricic4, S. Rajkovic3
1
tending from T4 to T6. Signs of spinal cord compression were Institute of Pathology, University of Belgrade, Serbia, 2 Institute of
notable. On gross examination, the removed lesion measured Pathology, Medical Faculty, University of Belgrade, Serbia, 3 Institute
4x2x0,5 and presented as an elongated smooth mass with an for Surgical and Orthopedic Diseases "Banjica", Serbia, 4 Institute for
homogenous brown cut surface. On histological examination, the Oncology and Radiology, Belgrade, Serbia
tumour consists of a double proliferation of mature adipocytes
admixed with abnormal vascular elements composed of irregularly Background & Objectives: Giant cell tumour of the soft tissue is a rare
thickened walls and flat regular endothelial cells. The patient had entity showing similar gross and histological features of giant cell tumour
an indolent, recurrence free outcome in a one-year follow-up of the bone. It most frequently occurs in the superficial and deep soft
assessment. tissue of the thigh, trunk, and upper extremities.
Conclusion: Spinal epidural angiolipomas are rare, but well recognized We report a case of 69-year-old female patient with 3 month long
causes of spinal cord compression. The infiltrative form can be radiolog- history of a rapidly growing, 6,4 cm nodule in the right breast region.
ically mistaken for a malignancy or aggressive vertebral haemangiomas. The lesion was fixed, nontender and adherent to the skin. The skin
Histologic diagnosis is usually evident, and the surgical treatment is cu- surface was focally ulcerated. Ultrasound and mammography con-
rative with excellent outcome. firmed aggressive lesion in the right breast. The clinical diagnosis
was breast carcinoma. Clinically there was no regional lymphadenop-
athy. Biopsy was indicated.
E-PS-23-039 Methods: In “frozen section” analysis malignant breast tumour with
GNAS mutations in differential diagnosis of fibrous dysplasia and giant cell component was diagnosed. On definitive pathological
myxomas slides primary diagnosis was corrected. Tumour was a well-
A. Tysarowski1, M. Wagrodzki2, K. Seliga1, T. Goryn4, R. Zub3, J.A. circumscribed multinodular lesion involving the dermis and
Siedlecki3, P. Rutkowski5, M. Prochorec-Sobieszek2 consisting of fibroblasts, histiocytes and osteoclast-type giant cells.
1
Department of Pathology and Laboratory Medicine, The Maria The nuclei of the giant cells were very similar to those of the mono-
Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, nuclear cells. A distinct fascicular pattern with focal storiform ar-
Poland, 2 Department of Pathology, The Maria Skłodowska-Curie rangement of spindle neoplastic cells was noted in the lesion.
Memorial Cancer Center and Institute of Oncology, Poland, Nuclear pleomorphism of mononuclear cells and rare mitotic figures
3
Molecular And Translational Oncology, The Maria Skłodowska-Curie were presented. Immunohystochemical analysis was indicated.
Memorial Cancer Center and Institute of Oncology, Poland, 4 Department Results: Immunohystochemistry studies revealed mononuclear and
of Soft Tissue/Bone Sarcoma and Melanoma, The Maria Skłodowska- multinuclear cells strong positivity for CD68 and vimentin and
Curie Memorial Cancer Center and Institute of Oncology, Poland, negative for cytokeratin, EMA, S-100 protein,SMA markers and
 Virchows Arch

CD 31. Ki 67 as proliferative factor was positive in less than 5% Background & Objectives: Metastatic melanoma to the anterior medi-
of cells. astinum is a rare event. Intrathoracic metastases usually occur as pulmo-
Conclusion: According to the histological and immunohystochemical nary nodules, solitary nodules, mediastinal and hilar lymphadenopathy,
appearance final diagnosis was giant cell tumour of the soft tissue. and pleural effusions. We hereby report a rare case of metastatic melano-
Now, 7 years later, the patient has no symptoms or signs of disease. ma presenting as an anterior mediastinal mass.
Methods: Tissue sections submitted after surgery were fixed in
10% neutral buffered formalin and embedded in paraffin. Some
E-PS-23-041 5‐micrometer sections were stained with hematoxylin‐eosin, and
Giant cell tumour of the tendon sheath: a clinicopathologic study of immunohistochemical stains for morphologic and immunohisto-
31 cases chemical evaluation.
A. Kilitci1, îF. Elmas2 Results: The patient was a 24-year old male who presented with
1
Ahi Evran University Medical Faculty, Dept of Pathology, Turkey, 2 Ahi dyspnea when recumbent. Physical examination revealed a non-ul-
Evran University Medical Faculty Dept of Dermatology, Turkey cerated, pigmented, skin lesion on the anterior chest, measuring 2.2 x
1.4 cm. CT scan showed an anterior mediastinal mass measuring 20 x
Background & Objectives: Giant cell tumour of the tendon sheath 14 x 10 cm. Excision biopsy of the skin lesion and tumour debulking
(GCTTS) is the second most common benign tumour of the hand after of the mediastinal mass were performed. Immunohistochemical stud-
ganglion cysts. Feet, knees and others, can also be involved. It is a slowly ies of both specimens show S100+, HMB45+, and Melan-A+. Ki-67
growing, usually painless lesion of soft tissues. The most widely accepted showed 60% proliferation. These findings are consistent with meta-
etiologic theories include trauma, infection, inflammation, osteoclastic static melanoma.
proliferation, metabolic disease, and neoplasia. We describe here a series Conclusion: This is a rare case of metastatic melanoma presenting as an
of 31 cases of GCTTS to try to define the epidemiological and clinico- anterior mediastinal mass. The usual disease course of metastatic mela-
pathologic findings of the disease. noma to the thorax shows mediastinal and hilar lymph node involvement,
Methods: The case records of all patients diagnosed to have GCTTS by which is not observed in our patient. This patient underwent tumour
our pathology department from 2009 to 2018 were analysed. We intro- debulking surgery to relieve compression symptoms but died a month
duced 31 cases of GCTTS in this study. Four cases of fibroma of the after due to tumour recurrence.
tendon sheath were excluded from the study. The age of patients, gender,
site of occurrence, size of the lesion, presenting symptoms, treatment
modality, histopathological reports, and recurrence were investigated, E-PS-24-002
and noted. Posterior mediastinal chondrosarcoma with unusual presentation as
Results: Ages of patients ranged from 14 to 74 years with most cases a cystic tumour mass: a case report
occurring in their thirties. There was a female predominance of 11 D. Udovicic-Gagula1, J. Redzepagic1, N. Bilalovic1
males to 20 females. The majority of patients had a painless subcu- 1
Department of Pathology, Clinical Center University of Sarajevo,
taneous palpable mass which gradually increased in size. The most Bosnia and Herzegovina
frequent site of the tumour was the finger in 61.3 % (n=19). The other
lesions were detected over the hand in 32.3% of the patients(n=10), Background & Objectives: Chondrosarcoma is a malignant cartilage-
foot in 3.2% (n=1), over the right knee (large joint) in 3.2% of pa- forming tumour of bone, usually arises within long bones or ribs.
tients (n=1). Among the small digit tumours the frequent affected site Although chondrosarcoma is the most common malignant tumour of
was the thumb. Single nodules (n=21) were more common than mul- the chest wall, it is still a rare entity. It is unexpected to find it in the
tiple (n=10). One male had maximum lesions on his left little finger posterior mediastinum, where neurogenic tumours are considered the
with 18 GCTTS. The most common preoperative clinical diagnoses commonest.
were GCTTS, fibroma, lipoma, schwannoma and epidermal cyst. Methods: We report a case of a 46-year-old woman whom presented with
Complete excision was the treatment in all of the cases. The tumours a complaint of intermittent pain in the right side of chest over three
were firm/elastic, usually encapsulated, regular in shape, with smooth months period. Chest X-ray and subsequent CT scan reveald
contour varying in size from 0.4 to 2.5 cm (average size 1.25 cm). wellcircumscribed, mainly cystic mass located in the upper right part of
Cut section of the tumour was grayish white mottled with yellow. the posterior mediastinum, without infiltration of lung parenchyma and
Histologic appearance of the tumours consisted of multinucleated only discreetly remodeling the ninth vertebrae and posterior part of rib.
giant cells, polygonal histiocytes, foamy histiocytes and hemosiderin Results: Histopathological examination of surgical resection specimen
laden macrophages. Immunohistochemically, CD68 and ki-67 were was consistent with a grade I chondrosarcoma with undoubtedly invasion
applied in some of the patients to support the diagnosis. Local recur- of bone.
rence was not seen. Conclusion: Because of possibility of local recurrence patient is recom-
Conclusion: We must distinguish GCTTS from other similar pathologi- mended close clinical and radiological follow up.
cal processes. A different histopathologic variation can be noticed be-
tween GCTTS involving the digits and large joints. The location and
the strict adherence of the tumour to the tendon or neurovascular bundles E-PS-24-003
may cause difficulties. Early diagnosis and treatment with wide excision Diagnosis of a thymic carcinoma in mediastinal biopsy
prevent local recurrence. C. Faria1, J. Fraga1, V. Almeida2, F. Ramalhosa 1, A. Lai1, M.B.
Pimentão1, R. Almeida1, H. Moreira1, R.C. Oliveira1, V. Sousa1, L.
Carvalho2
Sunday, 8 September 2019 – Wednesday, 11 September 2019 1
Centro Hospitalar e Universitário de Coimbra, Portugal, 2 Institute of
E-PS-24 | Thymic And Mediastinal Pathology Anatomical and Molecular Pathology, Faculty of Medicine of the
University of Coimbra, Coimbra, Portugal
E-PS-24-001
Background & Objectives: Mediastinal tumours are among the
Metastatic melanoma presenting as an anterior mediastinal mass
most difficult lesions examined by the Pathologist because many
O.P. Balisan1, G.N. Valloso1, L. Cale-Subia1
1 different types of lesions occur at this location. Thymic carcinoma
Philippine Heart Center, Philippines
Virchows Arch

is a rare, invasive mediastinal neoplasm with tendency to metas-

Sunday, 8 September 2019 – Wednesday, 11 September 2019
tasize. It represents 1% of the anterior mediastinal tumours and
E-PS-25 | Uropathology
occurs in all ages but more frequently between 30 and 60 years,
with a slightly male predominance. Diagnosis may be threattened
by mediastinal methodology of sampling.
Methods: Case report: 76-years-old woman presented chest pain, dys- E-PS-25-001
pnoea, cough, astenia and anorexia during seven months. PET scan re- EBV positive squamous cell carcinoma of the urinary bladder: a case
vealed a malignant mass in the superior and anterior mediastinum with report
well delineated borders and without evidence of disease at other levels. G. Richter1, C. Schmitt2, M. Baumann3
1
Mediastinoscopy was performed for diagnosis. Institute of Pathology, Hameln, Germany, 2 GenOPath, Bonn, Germany,
3
Results: Histopathological study of small fragments accounting for Sana Klinikum Hameln-Pyrmont, Germany
4mm2 revealed a neoplasia composed of smooth-countered islands
of large polygonal cells with hyperchromatic nuclei and eosinophilic Background & Objectives: Tobacco smoking is an important risk factor
cytoplasm in a fusocellular stroma infiltrated by scattered chronic for squamous cell carcinoma of the bladder. Moreover, it is relatively
inflammatory cells. In immunohistochemistry, tumoral cells had ex- common in the tropics and is associated with Schistosoma haematobium
pression of CK5.6, CK8.18, p63 and there were also positivity for infection. Until now Epstein-Barr virus (EBV) genomic material was not
CD20 (B lymphocytes) and CD3 (T lymphocytes). CD5, CD117 identified in a case of squamous cell carcinoma using polymerase chain
and CD10 were not expressed. The diagnosis of thymic carcinoma reaction (PCR) or hybridisation. We report a case of squamous cell car-
was reported. cinoma in the bladder with positive detection of EBV specific DNA by
Conclusion: Thymic carcinoma even with negativity for CD117 using real-time
was favoured as thymoma was excluded due to the organoid pat- Methods: We present a case of a 84 years old caucasian female with a
tern described. Clinically, thymic carcinoma is usually not associ- solid tumour of the bladder. Following histological examination of trans-
ated with paraneoplastic syndromes. This patient did not present urethral resection of the urinary bladder after routinely H&E-staining
other lesions in the mediastinum and the lungs, supporting the shows undifferentiated cells. Immunhistochemistry and molecularpatho-
diagnosis. logic investigations using PCR with following sequencing were per-
formed. DNA was isolated from the histological sample with the
QIAsymphony DSP DNA Mini Kit (QIAGEN). EBV was detected by
E-PS-24-004 real-time PCR using the artus® EBV RG PCR Kit (QIAGEN, Hilden)
Ectopic ACTH-producing thymic typical carcinoid tumour: a case according to the manufacturers protocol.
report Results: Routinely H&E-staining poorly defined islands of undifferenti-
J. Filipe1, T. Ferro2, C. Costa3, V. Leite3, F. Cunha1,2 ated cells were detected. The tumour cells have uniform, vesicular nuclei
1
Serviço de Anatomia Patológica, Instituto Português de Oncologia de with prominent nucleoli. In immuohistochemistry using the Roche
Lisboa Francisco Gentil, Lisbon, Portugal, 2 Faculdade de Ciências benchmark XT we identify cytokeratin 5/6 and p63 and a negative reac-
Mèdicas da Universidade Nova de Lisboa, Lisbon, Portugal, 3 Serviço tion using anti-GATA3 and anti-CK 20-antibodies. This seems to be the
de Endocrinologia, Instituto Português de Oncologia do Porto Francisco morphologic correlation of a poorly differentiated non-keratinizing squa-
Gentil, Porto, Portugal mous cell carcinoma.The PCR analysis revealed positivity for EBV.
Conclusion: This is the first case of squamous cell carcinoma of the
Background & Objectives: Thymic carcinoid is a rare entity, may be bladder with positive detection of Epstein-Barr Virus (EBV). The predic-
associated with endocrine manifestations and part of the spectrum of tive value of this detection is now unclear, and more studies are needed to
multiple endocrine neoplasia syndrome type I (in 25%). There are investigate the potential role of EBV squamous cell carcinoma carcinoma
few data regarding the prognosis of this entity, but propensity for of the bladder.
recurrence, lymph node and distant metastasis have been described.
Methods: We describe the clinical-pathologic features of an unusual
case of thymic typical carcinoid tumour, with ectopic ACTH E-PS-25-002
secretion. Urinary bladder cancer in Gwagwalada, Abuja, North-Central,
Results: A 27-year old man, without familial history of MEN1, Nigeria
presented with facial enlargement, asthenia, insomnia, and muscle O. Oluwole1
1
atrophy. Laboratory data revealed a 24-hour urinary free cortisol University of Abuja, Nigeria
measurement of 891μg/24h (NR 10-80μg/24h), plasma ACTH of
110pg/mL (NR <46pg/mL) and serum potassium of 2,8mEq/L Background & Objectives: Bladder cancer is the 7th most common
(NR 3.5 to 5.5mEq/L), featuring a Cushing’s syndrome. Complete cancer worldwide, accounting for 3.2% of all cancers.It is considerably
Imaging evaluation found a mediastinal mass. A 3cm infiltrative more common in males than in females, with an estimated 260,000 new
white-brown firm tumour with pericardium invasion was excised. cases occurring each year in men and 76,000 in women worldwide.
Microscopically it had an organoid pattern, with trabeculae and To determine the histopathological pattern of bladder cancer in our envi-
nests surrounded by a delicate vasculature, without cell atypia, mi- ronment and to compare with similar research work elsewhere.
totic activity nor necrosis. Neoplastic cells were immunoreactive for Methods: This is a 5-year retrospective histopathological study of blad-
AE1/AE3, CAM 5.2, Synaptophysin, Chromogranin A, CD56, and der cancer seen between 2005-2009 in the Department of Histopathology,
ACTH. Final diagnosis was thymic typical carcinoid tumour with University of Abuja Teaching Hospital, North-Central Nigeria. All the
ACTH secretion. The patient underwent radiotherapy after surgery Haematoxylin &Eosin stained slides and paraffin embedded blocks were
and several lymphadenectomies due to metastatic disease. He died 6 retrieved and studied. The relevant clinical data such as the age, sex, site
years after the initial diagnosis of disease progression. of lesion and clinical summary were extracted from the histology request
Conclusion: Ectopic ACTH-producing thymic typical carcinoid tu- forms.
mours should be considered in the context of an anterior mediastinal Results: A total of 13 patients (10 males and 3 females) with bladder
tumour associated with endocrine manifestations even with low- cancer were seen during the period of study. The male to female ratio is
grade histological features. 3.3:1. The mean age was 65 years. The most common histological type of
 Virchows Arch

bladder cancer in our environment is urothelial carcinoma no other his- Results: The patient underwent surgery: Radical prostatectomy.
tological types was seen in this review. Pathology report showed: Cribriform glands, sheets of individual cells,
Conclusion: Although, Gwagwalada is in the schistosomiasis endemic cords, solid nest cells and comedonecrosis, Gleason score 9 (4+5) com-
belt, the histological type of bladder cancer (urothelial carcinoma) seen in bined with glans lined by tall columnar pseudostratified epithelium, elon-
this review do not seem to reflect this as reported in similar studies. gated nuclei with severe atypia, prominent nucleoli and mitotic figures.
Therefore, there is need to further study the role of Schistosoma infesta- For all this reasons the final diagnoses was: Mixed adenocarcinoma of the
tion and squamous cell carcinoma of the bladder in our environment. prostate: Acinar adenocarcinoma Gleason score 9 (4+5) associated to
Ductal adenocarcinoma.
Conclusion: Mixed adenocarcinoma of the prostate accounts for approx-
E-PS-25-003 imately 2.6 - 3% of all prostate cancers. Most cases combined acinar
Sampling of radical prostatectomy specimens: complete vs partial adenocarcinoma Gleason score 9- 10 and ductal adenocarcinoma. This
sampling methods kind of mixed pattern a is more aggressive than the usual adenocarcinoma
A.R. Paz1, A. Billis2, L. Freitas1, L. Costa1, I. Barreto1 with higher risk of recurrence after radical prostatectomy. The ductal
1
Dep. Anatomic Pathology, School of Medical Sciences, State University component often elicits desmoplastic reaction with hemorrhage, edema
of Campinas (Unicamp), Brazil, 2 State University of Campinas - and inflammation.
Unicamp, Brazil
E-PS-25-005
Background & Objectives: Complete prostate sampling most accu- Acantholytic penile intraepithelial neoplasia
rately provides prognostic parameters. However, it demands labor, C. Beggan1
1
time and financial expense due to a high number of paraffin blocks St George's Hospital London, United Kingdom
which is particularly important in some countries. In a retrospective
study, we compared several partial methods to a series of 113 step Background & Objectives: Penile Intraepithelial Neoplasia (PeIN) is a
sectioned and completely processed prostates aiming to find the one recognised dysplastic precursor to penile squamous cell carcinoma. PeIN
with lower number of paraffin blocks but higher prognostic is subcategorised into differentiated and undifferentiated forms that vary
parameters. in morphology and relationship to high risk HPV infection.
Methods: 1: only posterolateral quadrants (PLQs); 2: only anterolateral Undifferentiated PeIN (uPeIN) is characterised by full thickness squa-
quadrants (ALQs); 3: all quadrants (Qs) of transverse section (TS) but mous atypia with loss of polarity, basaloid morphology and frequent
skipping one TS; 4: alternating only PLQs and only ALQs; 5: all Qs of atypical mitoses. UPeIN is related to high risk HPV infection and as such
predominant side in needle biopsy (NB) plus contralateral PLQ skipping shows diffuse strong positive staining with p16 immunohistochemistry.
one TS; 6: all PLQs plus ALQ of predominant side in NB skipping one Methods: This case describes a patient with both classic uPeIN and a
TS; 7: all PLQs and the ALQ skipping one TS of predominant side in NB separate but adjacent acantholytic precancerous abnormality, designated
plus contralateral PLQ skipping one TS. Acantholytic PeIN.
Results: Methods 4 and 7 showed the best results. In both methods, Results: This 72year old man presented with redness around the urethral
there was a 50% reduction of paraffin blocks with a detection of meatus. He underwent perimeatal glans excision which showed multifo-
positive margins and extraprostatic extension of 81.6% and 77.2% cal areas of classic uPeIN on the glans surface and extending into urethra.
in Method 4, and 89.8% and 82.5% in Method 7, respectively. Also present on the glans surface were foci of acantholysis. The
Invasion of the middle and distal portion of the seminal vesicle intraepithelial bullae were lined by large cytologically malignant
(SV) was always associated with invasion of the proximal portion, keratinocytes with similar morphology to those seen in the area of
and vas deferens invasion occurred only when the proximal portion uPeIN. p16 was positive in both areas of classic uPeIN and in the cells
of the SV was invaded. lining the acantholytic bullae.
Conclusion: It was consensus in a 2009 ISUP meeting that sampling of Conclusion: Acantholytic precancerous squamous lesion have previous-
radical prostatectomy specimens may be complete or partial. In methods ly been described in skin and oral cavities. This is the first described case
4 and 7 we obtained a 50% reduction in number of paraffin blocks and the of PeIN showing acantholytic morphology, which may represent a variant
highest percentage of prognostic parameters. Sampling of SV may be of uPeIN. Acantholytic (pseudoglandular) sqaumous cell carcinoma of
restricted to the proximal portion, and sampling of the vas deferens is the penis is a recognised subtype and this acantholytic PeIN may repre-
not necessary. sent a precursor to this rare cancer.

E-PS-25-004 E-PS-25-006
A curious case of mixed adenocarcinoma of the prostate: a case re- Coexistence of prostatic adenocarcinoma and mantle cell lymphoma
port and literature review T. Lakic1,2, J. Ilic Sabo1,2, A. Ilic1,2, Z. Vrekic2, M. Panjkovic1, D. Cuk2
V. Caamaño1, R. Ruiz1, E. Camacho1, A. Viguri1, N. Barriobero1, 1
University of Novi Sad, Faculty of Medicine, Serbia,
L. Lorente1, A. Perez1, I. Gorostiaga1, A. Martinez1 2
Clinical Center of Vojvodina, Novi Sad, Center for Pathology and
1
Araba University Hospital, Spain Histology, Serbia

Background & Objectives: Prostate cancer is the second most common Background & Objectives: Adenocarcinoma is the most common pros-
malignancy. Acinar adenocarcinoma is one of the most common variants. tatic malignancy for which clinical management Gleason score and recent
However, few cases combined acinar adenocarcinoma with and ductal updates in prostate cancer staging (ISUP/WHO) plays critical role.
adenocarcinoma. Is important to make differential diagnoses with pros- Mantle cell lymphoma (MCL) results from malignant transformation of
tatic intraepithelial neoplasia because it has a better prognosis correspond- a B lymphocyte in the outer edge of lymph node follicle with overexpres-
ing to Gleason score 6 (3+3). sion of cyclin D1, tipically. Our objective was to present a case of patient
Methods: 69 years old man with a history of urinary tract symptoms and with coexistenced tumours.
haematuria over the last two months. Physical exam showed an abnormal Methods: We report the case in which hematoxylin and eosin (HE) as well
digital rectal examination. Serum PSA level was 20ng/ml. MRI-guided as immunohistochemical stainings (IHC) showed coexisting tumours- pros-
biopsy was performed and showed: Acinar adenocarcinoma of the pros- tatic adenocarcinoma and MCL. A 68-year-old man without remarkable
tate, Gleason score 8 (4+4). medical history was admitted to our hospital for elective radical
Virchows Arch

1
prostatectomy because adenocarcinoma shown earlier due to prostate core National Medical Bohomolets University, Ukraine, 2 Institute of
biopsy. Computer tomography detected enlarged retroperitoneal lymph Urology, Ukraine, 3 National Academy of Medical Sciences of Ukraine,
nodes. As a routine part of this surgical procedure, lymph nodes were Ukraine
removed.
Results: Having performed thorough histological examination, HE sec- Background & Objectives: Absence of strict morphological criteria and
tions confirmed the diagnosis of prostatic adenocarcinoma, Gleason variable immunoreactivity of renal tumours with eosinophilic cytoplasm
score3+4=7, ISUP/WHO grade group2, measuring about 30% of prostat- make its differential diagnostics difficult. Differentiation of oncocytoma
ic parenchima. Lymph nodes microscopic analyses showed unexpected and chromophobe cell carcinoma requires application of such markers as
pattern consisted of small lymphoid cells, some with irregular nuclear Vimentin, C-kit (CD117), CK7, CD10. We report statistics of tumour
contours centrocyte-like, with wide mantle zone and hyalinized blood immunoreactivity in clinical cases which were observed in our institution.
vessels. IHC showed positivity for CD20,bcl2,CD5,CyclinD1 and Methods: Operative material from 19 patients (26-69 years old), with
CD43 staining, while CD3,CD10 and bcl6 were negative. Ki67 expressed clinically diagnosed renal mass and eosinophilic tumour histopathology
in~20% cells. According to morphological pattern and IHC staining di- was investigated. Hematoxylin and eosin staining and immunohisto-
agnose of MCL was set. chemical markers Vimentin (Vim3B4), CD117(CD7272), CD10(56C6)
Conclusion: A prostate adenocarcinoma can extremely rarely be in co- were used for verification of diagnosis.
existence with undiagnosed lymphoproliferative disease, as in our case Results: 21% of cases (n=4) demonstrated typical features of a chromo-
with non-Hodgkin mantle cell lymphoma. phobe renal cell carcinoma with Vimentin positive in 25% cases, CD117
positive in 67% cases, CD10 positive in 66% cases. In 21% of cases (n=4)
histopathology of a renal oncocytoma has been observed with Vimentin
E-PS-25-007 negative staining, CD117 positive reaction in 67% and CD10 negative
Plasmacytoid and nested variant invasive urothelial carcinoma: case staining. 6 tumours (32%) had appearance of papillary cell renal cell
report carcinoma (eosinophilic variant), and 5 tumours (26%) had appearance
T.C. Savli1, O. Okcu2, T. Bolme Savli3, B. Yeni4, K. Behzatoglu5 of clear cell renal cell carcinoma.
1
Istanbul Training and Research Hospital, Turkey, 2 Recep Tayyip Conclusion: In our study, tumours with eosinophilic morphology
Erdogan University Education and Research Hospital, Turkey, show overlapping immunoreactivity. The usefulness of Vimentin
3
Bagcilar Training and Research Hospital, Turkey, 4 University of for differential diagnostics of tumours with eosiniphilic appearance
Health Sciences, Department of Pathology, Turkey, 5 Acibadem remains controversial. Panel for differential diagnostics of eosino-
Healtcare Group, Turkey philic renal cell tumours should be improved by some additional
markers.
Background & Objectives: Bladder cancer cases are originated mostly
from epithelium. Urothelial carcinomas accounts for 85-90% of epitheli-
um originated cancers. Different morphological variants are observed E-PS-25-009
about 10-25% of cases. Due to the different prognostic significance and Histologically confirmed distant metastatic urothelial carcinomas
treatment modalities, these variants should be recognized and reported in from the urinary bladder: a retrospective review of one institution's
pathology reports. 16-year experience
Methods: A 72-year-old male patient was admitted to the urology poly- J. Lee1, Y. Yoo1, E. Choi1, H.S. Park1, S. Park1, M. Cho1, S.H. Sung2
1
clinic with the complaint of bleeding from the urine. In microscopic Department of Pathology, Ewha Womans University College of
examination, tumoral cells with eosinophilic cytoplasm, small Medicine, Seoul, Republic of Korea, 2 Department Pathology Ewha
hyperchromatic, centrally or eccentrically located nucleus was observed Womans University Mokdong Hospital, Republic of Korea
in a loose or myxoid stroma. Small nests forming tumoral cells with a
benign appearance was observed near these areas. Pancytokeratin and Background & Objectives: Bladder cancer is the seventh most common
CD138 was positive in the cells which invaded the muscle layer. Our case cancer. 90% cases are urothelial carcinoma. Tumour size, stage, grade, the
was reported as invasive urothelial carcinoma with plasmacytoid and presence of lymphovascular invasion (LVI) or perineural invasion (PNI)
nested features. have a significant impact on prognosis, risk of recurrence, and metastasis.
Results: The high metaplastic capacity of the bladder urothelial epitheli- Distant metastasis of urothelial carcinoma after radical cystectomy is
um and its origin from different embryological layers may lead to very common, but histologic confirmation for metastatic lesions has not been
different differentiations in invasive urothelial carcinomas. The performed routinely. In this study, we present clinicopathologic charac-
plasmacytoid variant can accompany %50 of high-grade urothelial carci- teristics of 15 cases of histologically confirmed metastatic urothelial car-
noma cases. The nested variant is composed of cytologically bland tu- cinomas of the urinary bladder.
mour cells with a nesting growth pattern. Therefore, the differential diag- Methods: Retrospective review of 744 patients who underwent radical
nosis is nephrogenic adenoma and Von Brunn islands. As in our case, cystectomy for primary urothelial carcinomas of the urinary bladder dur-
multiple variants can be seen together in rare cases. ing 16-year period (2002 to 2018) was conducted. Fifteen patients were
Conclusion: Most frequently squamous, glandular and micropapillary selected who had histologically confirmed distant metastases. Every HE
variants are reported in the literature, while plasmacytoid and nested slides were reviewed and the stage, grade and histologic variants were
variants are rarely detected. Plasmacytoid and nested variant urothelial reclassified according to the Cancer Staging Manual of the AJCC, 8th
carcinomas are aggressive tumours due to their early invasion, lymph edition and 2016 WHO/ISUP system, respectively. Clinical data were
node and distant organ metastasis capacities, and are often advanced at obtained from medical records.
the of diagnosis. Results: Fifteen patients (M:F=12:3) were identified. The mean age was
62.1 years. The average interval between the first diagnoses and distant
metastases was 36.6 months (range 0-123 months). Average follow-up
E-PS-25-008 was 55.9 months (range 5–151 months). The metastases occurred in the
Utility of Vimentin in immunohistochemical differential diagnosis of lung (n=5), lymph node (n=4), liver (n=2), bone (n=2) colon (n=1), and
renal tumours with eosinophilic appearance adrenal gland (n=1), respectively. Histologic variants include discohesive
L. Zakhartseva1, A. Romanenko2,3, V. Baranovska1, L. Nekrasova1 (n=3), squamous (n=2), micropapillary (n=1), sarcomatoid (n=1), and
 Virchows Arch

alphafetoprotein-producing (n=1) features (8/15, 53%). Ten showed LVI Results: Positive PAS staining was found both in the tissue of the prostate
or PNI (10/15, 67%). gland and in the secret. Strongest intensity of the signal was found in
Conclusion: The frequency of histologic confirmation for distant glands filled by secret. Corpora amylacea and the secret of the PCa glands
metastatic lesions is very rare. In this retrospective slide review, were PAS-negative. BPH tissue had a weak alcian blue staining intensity.
histologic variants showing aggressive clinical behaviour and LVI The secret of PCa glands was very positive for alcian blue staining. We
or PNI are frequently observed in the primary urothelial carcinomas indicate the presence of higher amount of acid mucopolysaccharides in
of the urinary bladder. Thorough histologic evaluation of the prima- the connective tissue component of PCa.
ry urothelial carcinoma of the urinary bladder is needed for Conclusion: Changes in the carbohydrate composition of the prostate
predicting clinical outcome. tissue during carcinogenesis were found. It manifests in reduced amount
of glycosaminoglycans and increased amount of acid mucopolysaccha-
rides in both the secret of the glands and the tumour tissue.
E-PS-25-010
Sarcomatoid renal cell carcinoma (carcinosarcoma) of the left kidney
with extension to the spleen: a case report E-PS-25-012
E. Koniaris1, I. Nikolopoulos1, K. Tsiardis1, E. Moula1, G. Kafiri1 Primary malignant melanoma of the urinary bladder: a case report
1
"Hippokratio" General Hospital of Athens, Greece S. Aydin Mungan1, G. Teoman2, I. Saygin2
1
Background & Objectives: We report a rare case of high grade Karadeniz Technical University School of Medicine Pathology
sarcomatoid renal cell carcinoma (carcinosarcoma, CS) of the left Department, Turkey, 2 ESP, Turkey
kidney. To our knowledge, only a limited number of such cases
have been described so far. CSs are highly malignant tumours, Background & Objectives: A primary malignant melanoma of the
composed of both mesenchymal and epithelial components. Our genitourinary tract is a rare lesion that accounts for only 0.2% of all
case was characterised by its focal extension to the spleen. CSs melanomas. Rather than being a primary lesion, malignant melano-
were dived into three groups: a) collision (coincidentally arise), b) mas of the bladder are more commonly metastatic lesions, which
combination (from a pluripotential cell) and c) composition tu- originate from a distant primary site. We report a case of amelanotic
mours (from the same tissue). malignant melanoma of the bladder, which mimics high grade
Methods: Our patient admitted to the hospital with hematuria and urothelial carcinoma.
left flank pain, underwent abdominal CT, which revealed a solid Methods: The surgical specimens were formalin-fixed and paraffin em-
mass on the upper pole of the left kidney measuring 7cm. bedded. The sections were stained with routinary H&E. Immunohisto-
Decision of a radical resection of the left kidney was taken and chemistry was performed.
we received a surgical specimen measuring 10,5X6,5X6,7 cm and Results: A 59-year-old woman was admitted to the department of
of weight 1640gr, the left adrenal gland m.d. 3cm, and the spleen general surgery for inguinal hernia. İncidentally, 13x12 mm mass in
measuring 10,2X8X3,2cm. On dissection, a whitish/brownish in the anteroinferior wall of the bladder was demonstrated in tomogra-
hue tumour was recognized, measuring 7X5X5cm. phy. Transurethral resection of the bladder was performed. The
Results: Two elements were recognized, the first a renal cell carci- spesmen was collectively 1.5 cm in diameter. In microscopic eval-
noma with a papillary/follicular growth pattern and the other uation, the tumour was predominantly composed of spindle cell
sarcomatoid with either spindle or pleomorphic cell growth pattern, infiltration. Immunohistochemical study showed that tumour cells
with bizarre morphology and neoplastic giant cells , severe pleo- were positive for S-100 and Melanoma triple marker, and negative
morphism and multilobulated nuclei, with abundant cytoplasm. The for GATA 3, desmin and CD 117.
lesion showed many mitosis, lot of them atypical, and areas of Conclusion: Malignant melanoma in the bladder is very rarely seen. It
necrosis. The neoplasm was highly invasive affecting the perirenal must be kept in mind that we may witness malignant melanoma, partic-
fat and the spleen. The adrenal gland or the vessels of the hilum ularly the amelanotic type, in the urinary bladder. Therefore, a careful
were not affected. review of histological features and performing necessary immunohisto-
Conclusion: CSs have been described in many anatomical sites, chemical staining procedures for S-100 and HMB-45 are very important
but very few have been reported in the kidney. CSs are known in achieving a correct diagnosis.
to be rapidly progressive tumours, with relapses, with poor out-
come and their survival is yet to be determined.
E-PS-25-013
Intrarenal adrenal cyst presenting as a renal mass: a case report
E-PS-25-011 S. Aydin Mungan1, G. Teoman2, E. Cakir2
1
Prostate cancer leads to a change in the composition of tissue Karadeniz Technical University School of Medicine Pathology
carbohydrates Department, Turkey, 2 ESP, Turkey
A. Romaniuk1, A. Piddubnyi1, M. Lyndin1, V. Sikora1, N. Gyryavenko1,
R. Moskalenko1 Background & Objectives: Ectopic intrarenal adrenal tissue can be
1
Sumy State University, Medical Institute, Pathology Department, found in 6% of general population. The site of its apperance is closely
Ukraine related to the migration of primordial adrenal cells in the course of organ-
ogenesis. Occasionally, diagnosis of adrenal rest is difficult. If detected,
Background & Objectives: The objective of the investigation is they often need to be differentiated from neoplastic lesions. We present a
following - to study the changes in the composition of the carbo- patient diagnosed as intrarenal adrenal cyst presenting as a renal mass.
hydrate components of prostate cancer tissue (PCa). Methods: The surgical specimens were formalin-fixed and paraffin em-
Methods: 60 PCa samples (30 samples of PCa with intraluminal bedded. The sections were stained with routinary H&E. Immunohisto-
inclusions (prostatic calculi and corpora amylacea) and 30 without chemistry was performed.
them) were used for study. 20 samples of benign prostatic hyper- Results: A 31-year-old woman suffering from recurrent urinary tract
plasia tissue were used as control. All samples were examined by infection.94x85 mm well-defined hyperdense mass in the right kidney
hematoxylin-eosin staining and by histochemistry (PAS reaction, was demonstrated in tomography.Laparoscopic cystectomi was per-
alcian blue staining at pH 2.5). formed. Macroscopically; collectively 5 cm diameter tissue samples in
Virchows Arch

the view of the cyst wall were admitted to our pathology department. (Gleason score 3+4, pT2N0). In 8 isolated lymph nodes no metastatic
Microscopically, the tissues compatible with the cyst wall were normal spread of adenocarcinoma was found, however, architecture was
adrenal cortical tissue. Adrenal cortical cells were positive with inhibin A, disfigured.
Melan A and focal synaptophsin and negative for EMA, Pax 8, CD 10 Case 2: In a 65- year- old male patient, localized prostatic adenocarcino-
and RCC. ma (Gleason score 3+4, pT2N0) was diagnosed. In combination with
Conclusion: The present report describes a rare case of adrenal cyst in a radical prostatectomy, 2 enlarged regional lymph nodes with possible
background of ectopic intrarenal adrenal tissue, which clinically and ra- tumoral infiltration were removed.
diographically mimicked a renal mass such as clear cell carcinoma and Results: Case1: H&E stains of the lymph nodes revealed large follicles
clear cell malignant melanoma. containing atypical centrocytes with large, irregular nuclei and rare
centroblasts. Histological and immunohistochemical analysis concluded
follicular lymphoma B cell- immunophenotype, low grade, as additional
E-PS-25-014 malignancy. Case 2: On H&E stains of the lymph nodes, no metastases
Paratesticular high grade myxoid liposarcoma: a case report from prostatic carcinoma were observed, but instead, diffuse infiltration
S. Aydin Mungan1, A. Cicek Malat2, I. Saygin2, G. Ay Haldiz2 of the nodes with small lymphatic cells was found. Histological and
1
Karadeniz Technical University School of Medicine Pathology immunohistochemical analysis confirmed the diagnosis of small lympho-
Department, Turkey, cytic lymphoma B cell- immunophenotype (B-SLL).
2
ESP, Turkey Conclusion: Despite the fact that regional lymph nodes in cases of pros-
tatic adenocarcinoma are removed in order to estimate metastatic spread
Background & Objectives: Paratesticular sarcomas are rare and account of the tumour, it is important for the pathologist to be alert of other
for about 2% of all soft tissue sarcomas. Paratesticular myxoid malignancies arising in the lymph nodes to ensure patient’s benefit.
liposarcomas are considered very rare, accounting for approximately
3.3% of liposarcomas in this anatomic location and is seen in the
fourth-fifth decade. We report a rare case of high grade myxoid E-PS-25-017
liposarcoma in a young adult’s paratesticular tissue. Bone metastasis revealing renal carcinoma related to Xp11.2 trans-
Methods: The surgical specimens were formalin-fixed and paraffin em- location in an elderly patient
bedded. The sections were stained with routinary H&E. Immunohisto- F. Chadi1, N. Bourhroum2, N. Mahassini2
1
chemistry was performed. Pathology Department of Mohamed V Military Teaching Hospital,
Results: A 31-year-old man was admitted to the hospital with pain in his Rabat, Morocco, 2 Pathology Department of Ibn Sina Universitary
chest and hand mass in this area. In the examination, it was learned that he Hospital, Rabat, Morocco
had a mass in the testicular region for 2 years. Orchiectomy and mass
excision were performed. Macroscopically mass was necrotic, solid and Background & Objectives: Renal carcinoma related to the Xp11.2 trans-
gelatinous. In microscopic evaluation,the tumour consisted of round cell location has long been known in childhood kidney cancer and young
populations and plexiform vascular structures in myxoid stroma. adult cancers. It is exceptional in the elderly subject. The aim of this work
Immunohistochemical studies showed that tumour cells were positive is to focus on this rare entity.
for Vimentin,CDK4,S-100(focal), and they were negative for MDM2, Methods: We report the case of an 80-year-old patient with psychosis.
SMA,Desmin,CD34 and p16. Who consulted for bone, lumbar and iliac pain. CT shows osteolytic
Conclusion: Myxoid liposarcoms are very rare malignant tumours lesions of metastatic appearance, the radiological assessment shows the
in paratesticular area. As in our patient, this tumour can be con- presence of a renal mass.
sidered benign because it has been present for a long time. In Results: Histological and immunohistochemical study performed on the
conclusion, if the patient would have been diagnosed earlier, he bone biopsy results in bone metastasis of renal carcinoma with Xp11.2
would have chance to be cured by mass excision. As a result, this translocation. It was the immunohistochemical study that showed the
rare entity should be kept in mind, which is very rare in young involvement of a translocation of the locus of the TFE3 gene located in
people. Xp11.2.
Conclusion: Renal carcinoma with translocation Xp11 was uncommon
in adults after 50 years, but probably often unknown because of little
E-PS-25-015 research. It seemed associated with a poor prognosis. Larger studies must
Prostatic adenocarcinoma and lymphoma- common malignancies, be carried out to optimise its specific management.
but uncommon coexistence
S. Masic1, M. Ulamec1,2, T. Regovic Dzombeta1,2, B. Kruslin3,4
1
Clinical Department of Pathology and Cytology "Ljudevit Jurak", E-PS-25-018
University Hospital Centre Sestre Milosrdnice, Zagreb, Croatia, New approaches in pathomorphological diagnosis in oncourology
2
Department of Pathology, School of Medicine, University of Zagreb, T. Pavlova1, V. Kulikovskiy1, I. Pavlov1
Zagreb, Croatia, 3 Department of Pathology and Cytology, Sestre 1
Belgorod State University
Milosrdnice University Hospital Center, Croatia, 4 School of Medicine,
University of Zagreb, Croatia Background & Objectives: The cancer diseases of kidney, bladder and
prostate are extremely common, and they demonstrate steady dynamics
Background & Objectives: Prostatic carcinoma is the second most com- of growth all over the world.
mon malignancy in male population. Also, Non- Hodgkin lymphoma is Methods: Tissues of patients with cancer (55 patients with kidney cancer,
well- known and common clonal lymphoproliferative malignancy. 35 patients with bladder cancer, 75 patients with prostate cancer) were
However, association of prostatic adenocarcinoma with incidental finding researched with additional usage of scanning microscope (SEM) "FE1
of lymphoma is rare and occurs from 0.2- 1.2 % of all cases of radical Quanta 200 3D" with console for elemental analysis.
prostatectomy with regional lymphadenectomy. We present 2 cases of this Results: The characteristic of depth of tumour’s spreading within
uncommon association. tissues, quantity of cells, their sizes, contacts between them, and
Methods: Case 1: After being diagnosed with prostatic adenocarcinoma, stages of formation of tumour embolus were given. The most rep-
a 61- year- old male patient underwent radical prostatectomy with region- resentative elements at verification of cancer were oxygen, sodium,
al lymphadenectomy and was confirmed having adenocarcinoma magnesium, phosphorus. The content of oxygen was in direct
 Virchows Arch

relation from the number of cells in clone. Initially, it exceeded the communicating cavities lined by a single layer of flattened cells
amount in tissues without tumour cells, and then it decreased. The and Hobnail cells. Degenerative changes were also present.
content of potassium increased in 1.5-2 times. Immunohistochemistry showed positivity for AE1/AE3 in the cystic
Conclusion: Scanning Electron Microscopy makes possible the epithelium and for desmin and vimentin in stromal cells. PAX8,
conduction of express diagnosis for determination of stages of TTF-1, CEA and CK20 were negative. The proliferation rate was
tumour growth, as well it makes premises for further study of 1-2%. Therefore, a renal cell carcinoma was excluded, and the final
pathogenesis of tumour’s growth, methods of pathomorphological diagnosis was adult cystic nephroma.
diagnosis and treatment. Conclusion: Differential diagnosis between multicystic adult
nephroma and renal cell carcinoma is extremely important.
Prognosis and treatment differ as multicystic adult nephroma is a
E-PS-25-020 benign unharmful condition with an excellent prognosis, whereas
Primary squamous cell carcinoma of renal pelvis without renal cell carcinoma has a poor prognosis.
nephrolithiasis history
Z.C. Olgun1, G. Kir1, A. Yildirim2
1
Istanbul Medeniyet University, Department of Pathology, Turkey, E-PS-25-022
2
Istanbul Medeniyet University, Department of Urology, Turkey Stromal Tumours of Uncertain Malignant Potential (STUMP)
S. Stifter1, R. Barbazza2, A. Cescato3, G. Dordevic1, S. Gasparic4
1
Background & Objectives: Primary squamous cell carcinoma (SCC) of Department of Pathology, Clinical Hospital Centre Rijeka, Croatia,
2
renal pelvis constitues less than 1% of renal neoplasms. There is high University of Trieste, Italy, 3 Laboratori Riuniti Trieste, Italy, 4 County
association between nephrolithiasis and primary SCC of renal pelvis. Hospital Pozega, Croatia
Methods: 71-year-old male patient presented with macrohematuria for
last 3 years. The patient had 30 years history of analgesic use and 50 Background & Objectives: Prostatic Stromal Tumours of Uncertain
years/pack smoking history. A CT scan revealed a solid mass which was Malignant Potential (STUMP) are non-epithelial mesenchymal spindle-
compatible with renal cell carcinoma in upper pole of left kidney. Renal cell origin prostate tumours classified as a specialized stromal tumour of
pelvic biopsy was diagnosed as high-grade carcinoma with extensive the prostate. They represent rare neoplastic proliferative lesions that ac-
squamous differentiation. He underwent left radical nefroureterectomy. cording to WHO classification together with prostatic stromal sarcoma
Results: On macroscopic examination, there were gray-white solid tumour (SS) comprise up to 0.2% of all malignant prostate tumours.
with ill-defined borders, 14cm in dimension and involving the upper and Methods: We present a case of patient clinically presented with symp-
middle pole of kidney and proximal ureter. Tumour invaded beyond gerota’s toms of acute urinary retention (AUR). Digital rectal examination (DRE)
fascia macroscopically. There were contiguous extention into the ipsilateral showed the presence of a pronounced prostatic hyperplasia and a trans-
adrenal gland microscopically. In spite of extensive sampling (sample per cm) urethral prostatic adenomectomy (TURPA) was performed. The primary
there were no clue of invasive and in-situ urothelial carcinoma. The tumour pathological evaluation was performed at Laboratorii Uniti, Italy and
was composed of SCC purely. Clinically PET-CT scan was unremarkable second opinion at the Department of Pathology, Clinical Hospital
except left kidney, and the tumour was immunhistochemically negative for Centre Rijeka, Croatia upon an incidental and unexpected diagnosis of
CK7, CK20 and GATA-3. For this patient there were no nephrolithiasis prostatic STUMP. It was morphologically discriminated based on follow-
history. Tumour reported as moderately differentiated primary SCC of renal ing criteria: stromal cellularity, presence of occasional mitotic figures,
pelvis (pT4 N0 Mx L1 V1 Rx). necrosis, and stromal overgrowth. Thorough immunohistochemistry
Conclusion: Primary renal SCC has challenging differential diagnosis, evaluation and tumour immunophenotyping was performed.
including high grade urothelial carcinoma with extensive squamous dif- Results: Presented tumour was immunohistochemically positive for
ferentiation and metastatic SCC. Extensive tumour sampling, CD34, Vimentin, progesterone and cytokeratin negative. It diffusely in-
immunhistochemistry and clinical evaluation have significance in terms filtrated the prostate gland and extend into adjacent tissues. Mitotic count
of differential diagnosis. was low, while focally marked cellular atypia was observed throughout
the lesion. The capacity of recurrence placed it into the group considered
to have frank neoplastic capacity. Therefore the clinical and further ther-
E-PS-25-021 apeutic management should be made keeping in mind the probability of
A rare case of an adult cystic nephroma progression into sarcoma.
I.A. Ungureanu1, A. Iliesiu1,2, L.A. Ursache1, D.I. Enea1 Conclusion: Currently, due to a small number of cases and consequent
1
University Emergency Hospital Bucharest, Romania, 2 Carol Davila follow up the recommended treatment algorithm does not exist.
University of Medicine and Pharmacy, Romania According to some authors and literature data, radical prostatectomy
seem to be the treatment of choice, especially in young patient or for
Background & Objectives: Cystic nephroma is a rare benign tumour extensive recurrent lesion. The presented case stresses out the need for
characterised by multiple cystic lesions of the kidney. It is usually seen in extensive sampling in order to fully appreciate tumour heterogeneity,
paediatric population under different names and most of the cases are because STUMP remains diagnosis by exclusion.
discovered incidentally. We report a case of an adult cystic nephroma
with further discussion on microscopic findings, differential diagnosis
and prognosis. E-PS-25-023
Methods: A 41-year-old female was hospitalized for left lumbar LELC of the ureter: a rare finding
pain with no family history of any kidney tumour. Laparoscopic M. Bercea1, A. Dema1, A. Stetco1, D. Herman1
1
total nephrectomy was performed and the specimen was sent for Emergency Clinical County Hospital "Pius Brinzeu" Timisoara,
gross examination. The microscopic analysis was performed on par- Romania
affin embedded tissue samples stained with hematoxylin-eosin.
Immunohistochemistry was completed for the following markers: Background & Objectives: Lymphoepithelioma is a malignant epitheli-
ki-67, Vimentin, Desmin, CD10, AE1/AE3, CK20, PAX8, CEA, al tumour of the nasopharynx. Tumours with similar morphological char-
EMA, TTF-1. acteristics which are found in other sites of the body are known as
Results: Gross examination revealed an encapsulated multicystic lymphoepitelioma-like carcinomas (LELC). Ureteral LELC is an ex-
mass in the left kidney. Microscopy showed cystic non- tremely rare tumour, with only 10 cases previously reported.
Virchows Arch

Methods: A 72-year-old male was admitted in our Urology department unlike when it occurs in adults. We report a case in a child with unusually
with left hydronephrosis due to a periureteral nodular mass, adjacent to aggressive behavior and a case in an adult with more indolent course.
the left renal hilum; the clinical suspicion was of lymph node metastasis. Methods: We report two cases of RCC Xp11: a 12-year-old girl with a
Excision of the mass was performed, followed up by nephroureterectomy 14-cm renal mass found incidentally, with lymph node involvement at the
2 months later. time of diagnosis, and a 45-year-old woman with an 8-cm renal mass
Results: The initial mass measured 46/30/27 mm and was greyish-white without extrarenal extension. Histologically, in both cases there were
on the cut surface. Histological sections revealed a nodular, relatively well large epithelioid cells with eosinophilic/granular appearance and focal
circumscribed tumour, with focally infiltrative margins in the surrounding vacuolation arranged in alveolar/nested growth pattern, predominantly.
fatty tissue, consisting of solid syncytial sheets of neoplastic epithelial No psammoma bodies were found.
cells, accompanied by an abundant lymphoid cell population, suggestive Results: In both cases, the diagnosis was confirmed by diffuse and strong
of LELC. The immune profile (positive for cytokeratin 7, cytokeratin 20, nuclear labeling for TFE3 by immunohistochemistry. A break-apart of the
GATA 3 and p63) is supportive for the urothelial origin of the tumour. TFE3 genes was identified by fluorescence in situ hybridization analysis
Conclusion: Considering that ureteral LELC is such a rare entity, in 62% and 72% of the evaluated cells, respectively.
recognising this type of tumour is extremely important in order to avoid Conclusion: The diagnosis Xp11 tRCC is not possible with the clinical
misdiagnosis with lymph node metastases, lymphomas or inflammatory and morphological findings exclusively, being essential to demonstrate
lesions, due to the completely different therapeutic management required the genetic alteration that characterises it: a translocation that takes place
for each of them. in the X chromosome and that produces a rearrangement in the TFE3
gene.

E-PS-25-024
A rare tumour in genitourinary system: presentation 2 cases diag- E-PS-25-026
nosed with large cell neuroendocrine carcinoma Small Cell Carcinoma (SCC) of urinary bladder: a case report
Y. Cakir1, M. Ozsen1, C. Uzun1, A.E. Bilici1 P. Tziakou1, G. Galanopoulos1, M. Nifora1, A. Zizi-Sermpetzoglou1
1 1
Erzurum Regional Training and Research Hospital, Turkey Department of Pathology, Tzaneio General Hospital of Piraeus, Greece

Background & Objectives: Primary neuroendocrine tumours in the gen- Background & Objectives: SCC of the urinary bladder is a rare but
itourinary system (GUS) account for 1-2% of genitourinary malignancies. highly aggressive malignancy. The mean age at the time of diag-
They have been separated to four groups as small cell neuroendocrine nosis is 66 years, with a male predominance and a history of
carcinoma, large cell neuroendocrine carcinoma (LCNEC), well- smoking.
differentiated neuroendocrine tumour, paraganglioma in WHO 2016 clas- Methods: We report a case of 65-year-old female who presented with
sification. LCNEC is the most of rare among them. hematuria and pelvic pain. Cystoscopy revealed a 5 cm polypoid mass at
Methods: Case 1: An 68-year-old man presented with a history of gross the lateral wall and trans urethral removal of bladder tumour (TUR-BT)
hematuria. CT revealed a 4x4 cm mass in the left posterolateral wall of the was performed.
bladder. PET-CT showed multiple metastatic lesions on lung, liver, bones. Results: The histopathological exam showed development of a carcino-
Transurethral resection was performed. ma, consisting of sheets of small-sized cells, invading the muscularis
Case 2: An 65-year-old man presented with a history of gross hematuria. propria. Coexisting areas of urothelial carcinoma and in situ urothelial
MR revealed that tumoral lesion that covering at left prostate lobe. carcinoma were also observed.
Transurethral resection was performed. Immunohistochemical analysis showed that tumour cells express
Results: The histological examination of the both of tumour were similar. immunopositivity to chromogranin, CD56, CK20(dot-like), CK7 and
Tumours were composed of large, polygonal cells, with a low nuclear/ TTF-1. Chest CT scan was normal, so the diagnosis of a Small Cell
cytoplasmatic ratio. Coarse chromatin and frequent nucleoli, brisk mitotic Carcinoma was made.
activity, necrosis was also present. Tumour cells were positive with Conclusion: SCC is a rare malignant neuroendocrine neoplasm of the
synaptophysin, chromogranin, CK 7, focal positive with CK 20 and urothelium that accounts for less than 1% of urinary bladder cancers.
GATA-3. HMWCK, PSA, TTF-1 were negative. A significant proportion of patients also present initially with meta-
Conclusion: The differential diagnosis includes metastatic LCNEC static cancer. It exhibits both epithelial and neuroendocrine differen-
from pulmonary or gastrointestinal primary sites, primary large cell tiation. Jones et al. showed that approximately 40% of patients with
lymphomas, high-grade prostatic carcinoma and undifferentiated SCC of the urinary bladder had positive TTF-1 staining. Therefore,
urothelial carcinomas. LCNEC in the GUS is a very rare, but its TTF-1 immunostaining cannot reliably distinguish between a lung or
diagnosis is important, due to its poor prognosis. As long as it is kept urinary bladder primary tumour and the distinction can be made only
in mind, it is easy to diagnose with the help of immunhistochemistry. by knowledge of the clinical setting. The overall prognosis is poor.
Cytotoxic chemotherapy plays a major therapeutic role in the treat-
ment of limited-stage and advanced-stage SCC of the urinary blad-
E-PS-25-025 der, while neoadjuvant therapy appears to improve survival.
Xp11 translocation renal cell carcinoma with TFE3 gene fusion: two
case reports to expand the clinical and morphologic spectrum
L. Barona García1, B. Ferri Ñíguez1, D. López Motos1, M. Biscuola1, Î E-PS-25-027
Girón Vallejo1, A. Salazar Nicolas1, M.I. Oviedo Ramírez1, M.I. Ortuño Foamy cell angiosarcoma localised to the pelvis: a rare case report
Moreno1, A. Caballero Illanes1, E. Martínez Barba1 R. Akpinar1, N. Comunoglu1, C. Demirdag2, I. Gurses1
1 1
Servicio de Anatomía Patológica, Hospital Clínico Universitario Virgen Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty,
de la Arrixaca Department of Pathology, Turkey, 2 Istanbul University-Cerrahpasa,
Cerrahpasa Medical Facult, Department of Urology, Turkey
Background & Objectives: The Xp11 translocation renal cell carcinoma
(Xp11 tRCC) is a recently reconognized subset of renal cell carcinoma Background & Objectives: Angiosarcoma is a malignant vascular tu-
(RCC) that belongs to the MiT family translocation RCC. Xp11 tRCC is mour, often seen in the head&neck of the elderly men. There are uncom-
an infrequent neoplasm that tends to appear at younger ages than other mon variants such as epithelioid, clear cell, granular cell, verrucous,
subtypes of RCC. The prognosis of Xp11 tRCC in children is good, pseudolymphomatous and signet-ring cell types. In addition, a rare form
 Virchows Arch

of angiosarcoma is the so-called foamy cell variant that has been de- R. Brandao1, A.C. Andrade2, G. Santos3, R. Souza2, C. Dias1, D.
scribed a few cases localized in the skin. Alvarenga1
1
Methods: A 58-year-old female patient referred with hematuria occasion- Laboratorio Alvarenga, Governador Valadares, Brazil, 2 Federal
ally. She had received radiotherapy 48 years ago with the diagnosis of University of Juiz de Fora - GV, Governador Valadares, Brazil, 3 Vale
dysgerminoma. Transurethral resection (TUR) of the bladder has been re- do Rio Doce University, Governador Valadares, Brazil
ported as angiosarcoma. After that, she has been undergoing total abdom-
inal hysterectomy, unilateral salphingo-oophorectomy and total cystectomy. Background & Objectives: Schistosomiasis is an infectious disease
Results: TUR specimen was included only mucosa of the bladder that endemic in Brazil and of broader global relevance. Despite high
had irregular vascular spaces lined with atypical endothelial cells. All rates of schistosomiasis, rates of genitourinary involvement by
organs of resection specimen were firm and infiltrated by tumour. Schistosoma mansoni (S. mansoni) are low. We report a case of
Microscopically, there were two growth patterns within tumour. Well- prostatic schistosomiasis mansoni identified incidentally in a pros-
formed vessels were just seen in the submucosa of the bladder and solid tatic adenocarcinoma patient’s biopsy. Current studies indicate a
islands were comprised foamy cells that had large, pale vacuolated cyto- possible association of schistosomiasis with the development of ad-
plasm and hyperchromatic nucleus. Solid islands were seen all layers of enocarcinoma, however, there are few cases present in current
the organs and soft tissue around them. Tumour cells were positive for literature.
ERG, CD31 and c-myc while HMB45, MelanA, PanCK, TFE-3, SMA Methods: Patient, 54 years old, Brazilian, was referred for a prostate
were negative. C-myc was negative with FISH. biopsy, given clinical suspicion of adenocarcinoma. Histopathological
Conclusion: Foamy cell angiosarcoma is a very rare entity and described analysis confirmed the diagnosis of usual acinar prostatic adenocarcino-
only cutaneous tissue with %10-20 overall survive in five years. This ma, Gleason 6 (3 + 3) present in two of the six samples. A chronic
variant has also not been described before in deep soft tissue or any granulomatous inflammatory process containing giant cells
organs in the literature. encompassing calcified eggs compatible with S. mansoni was additional-
ly observed.
Results: The findings of S. mansoni are common in liver and
E-PS-25-028 spleen, however, ectopic forms are of special importance in endemic
Adult-type granulosa cell tumour of the testis: a case report areas, such as Brazil. Studies suggest schistosome egg antigens are
O. Semerci1, M.S. Ayazoğlu1, R. Bedir1, H. Uzun2 capable of inducing oxidative stress and oncogenic phenotypes
1
Department of Pathology, Recep Tayyip Erdogan University, Medical through inactivation of the p27, a tumour suppressor gene, and
Faculty, Turkey, 2 Department of Urology, Recep Tayyip Erdogan genetic hyperactivation of B-CL2, an apoptosis inhibitory protein.
University, Medical Faculty, Turkey Therefore, the interaction of these factors is associated with the
development of malignant neoplasm.
Background & Objectives: One of the most common causes of infertil- Conclusion: The finding of prostatic schistosomiasis by S. mansoni con-
ity in young males are testicular neoplasms. Sex cord-stromal tumours comitant with adenocarcinoma is uncommon, being predominantly inci-
which include granulosa cell tumours are uncommon testicular tumours. dental in biopsies. More studies are needed to better evidence causal
Granulosa cell tumours divided into juvenile and adult type. Adult-type factors that explain the association between prostatic schistosomiasis
granulosa cell tumours are extremely rare and to the best of our knowl- and adenocarcinoma, with the objective of early diagnosis and better
edge, few than 50 cases have been reported to the date. Here, we present a prognosis of patients.
case of a 30-year old male with testicular mass.
Methods: A 30-year-old male patient presented with complaint of infer-
tility. Physical examination revealed a painless, palpable right testicular E-PS-25-030
mass. Serum AFP and HCG levels were within normal ranges. Primary synovial sarcoma of the testis
Azoospermia detected on spermiogram. Scrotal ultrasound revealed a A. Vlahova1, M. Genadieva-Yordanova1
1
4.2x3.5 cm heterogeneous solid mass lesion with a marked increase of Aleksandrovska University Hospital, Bulgaria
central and peripheral vascularity in the testicular parenchyma. Both
physical examination and radiological findings were consistent with a Background & Objectives: Synovial sarcoma occurs at any age, with
testicular tumour. A radical orchiectomy performed. peak incidence between 10 and 40 years of age and slight male predom-
Results: Macroscopically there was an intratesticular solid firm yellow- inance. Usually arises in the lower limbs but many other primary sites are
white tumour measured 3.8x2.6 cm. Histological examination demon- reported.
strated nests and cord composed of small cells with scant cytoplasm Methods: 68 years old man with testicular enlargement. CT found no
and coffee bean-like angulated and grooved pale ovoid nuclei which is remarkable changes in the other organs. Surgical excision /orchiectomy /
typical morphology of the of granulosa cells. There is few mitotic figures. followed by routine biopsy processing was performed with additional
There was no pleomorphism and necrose. Immunohistochemically, tu- immunohistochemistry.
mour cells were strongly positive for inhibin and vimentin and showed Results: Tumour replaced the normal structures of the testis with no
focal positivity for CAM5.2 while they were negative for PLAP, CD117, residual tissue left. The mass was 7 cm in diameter with fleshy
CD45, CD138 and S-100. The Ki-67 proliferation index of tumour was appearance and small areas of necrosis and hemorrhages.
low (%1-2). The case was diagnosed as adult-type granulosa cell tumour. Microscopy revealed proliferation of poorly differentiated round
Conclusion: The diagnosis of granulosa cell tumour is mostly based on cells with vesicular nuclei and predominantly nested growth pattern,
histopathological features. Our report emphasizes on this uncommon en- separated by delicate to abundant collagen; one area with hyaline
tity which is quite challenging in terms of diagnosis. Although adult-type change and vascular invasion. Immunohistochemically tumour cells
granular cell tumour is a very uncommon entity in testis compared to were negative for Smooth muscle actin, Desmin, Cytokeratin AE1-
ovary, it should be kept in mind when making a differential diagnosis AE3, MPO, CD34 and positive for CD 99 (perinuclear dot-like
on testicular tumours. reaction), CD 56, bcl-2 and TLE-1, focal positive reaction for
Calretinin. No genetic molecular analyses was performed /not avail-
able for soft tissue tumours in the country/.
E-PS-25-029 Conclusion: These findings were consistent with poorly differentiated
Prostatic schistosomiasis by schistosoma mansoni in a patient with synovial sarcoma of the testis - unusual primary site for this tumour,
prostatic adenocarcinoma: case report unfrequently reported in the patient’s age group.
Virchows Arch

E-PS-25-031 seminomas. Risk factors include cryptorchism, family history of TGCT,

Squamous cell carcinoma of the prostate following treatment with an and most important risk factor is presence of TGCT diagnosis in patient's
LHRH-agonist: a rare case of transformation of adenocarcinoma of history.
the prostate
R. Ayadi1, F. Gargouri1, N. Mansouri1, B. Laabidi1, A. Bouziani1, I.
Msakni1 E-PS-25-034
1
Pathology Department, Military Hospital, Tunis, Tunisia. University of Metanephric adenoma - case report in a 58-year-old woman
Tunis El Manar, Faculty of Medicine of Tunis, Tunisia O. Neagu1, G. Berdan2, C. Paranici1, A. Petrescu2, D. Diaconescu2, F.
Vasilescu3
1
Background & Objectives: Squamous cell carcinoma (SCC) of the University Emergency Hospital Bucharest, Romania, 2 "Prof. Dr. Th.
prostate accounts for less than 1% of all cases of prostate cancers. Burghele" Clinical Hospital, Bucharest, Romania, 3 "Victor Babes"
Squamous differentiation may arise subsequent to endocrine or radiation National Institute of Pathology, Bucharest, Romania
treatment, but it is very rare. To date, a few cases have been reported in the
literature. The aim of this study is to describe a case of SCC of the prostate Background & Objectives: Metanephric adenomas are rare benign ep-
developing in a patient with adenocarcinoma of the prostate following ithelial renal tumours that mainly affect middle-aged women. Less than
hormonal therapy. 200 cases have been reported in the English literature. We report a case of
Methods: We report, a case of a patient who was diagnosed with a 58-year-old woman who was admitted with an echographic diagnosis of
recurrence adenocarcinoma (ADK) of the prostate at the bladder, a right renal tumour.
treated with an LHRH–agonist and subsequently found to have Methods: We examined the right nephrectomy specimen that presented a
SCC. well circumscribed but not encapsulated, yellowish-grey, solid tumour of
Results: A 71-year–old male presented with lower urinary tract symp- 3/2/1 cm involving the upper pole of the kidney, right beneath the renal
toms and a PSA level of 2.7ng/ml. A diagnosis of Gleason 6 adenocarci- capsule.
noma of the prostate was made on biopsies. Treatment consisted on rad- Results: Histopathological examination revealed tightly packed tu-
ical prostatectomy and radiotherapy. 11 years later, he achieved a PSA bular and glomeruloid-like structures or solid areas composed of
nadir of 0.59ng/ml with hematuria. The cystoscopy with resection con- round cells with scant cytoplasm and hyperchromatic, overlapping
firmed recurrence tumour at the bladder. The patient began nuclei with inconspicuous nucleoli and mitoses. No capsule or
hormonotherapy (Triptoréline+Cyprotérone). 6 months later, he present- pseudocapsule, lymphovascular emboli or infiltration into the
ed again a hematuria. The histopathologic findings identified a SCC with perinephric adipose tissue or renal sinus fat was seen.
no ADK. Immunohistochemistry: WT1 and CD57 showed diffuse positivity
Conclusion: SCC of the prostate is an infrequent and aggressive malig- in tumour cells, AMACR, CK7, Chromogranin, Synaptophysin,
nancy. It is associated with a high incidence of recurrence and carries a AE1/AE3 and CD10 were negative in tumour cells with a Ki67
poor prognosis. of 1-2%.
Conclusion: Clinical and imaging findings are relatively limited so
MA is often misdiagnosed as renal cell carcinomas, renal cysts, and
E-PS-25-033 other kidney diseases. It is very important to make a histopatholog-
Synchronous seminoma of the right testis and mixed germ cell tu- ical differentiation between MA and other entities that share similar
mour of the left testis without history of cryptorchidism morphological features such as the solid variant of papillary renal
G. Kir1, T. Soylemez1, A. Yildirim2 cell carcinomas (PRCC) or epithelial-predominant nephroblastoma.
1
Istanbul Medeniyet University, Department of Pathology, Turkey, Immunohistochemistry is very helpful in distinguishing these enti-
2
Istanbul Medeniyet University, Department of Urology, Turkey ties. Clinical outcome is very good for patients with MA although
presence of regional lymph node metastases in a 7-year-old child
Background & Objectives: Bilateral testicular germ cell was reported.
tumours(TGCTs) are uncommon. The incidence of bilateral TGCTs is
%1-5 among all TGCTs.
Methods: A 23-year-old male patient, without a history of cryptorchi- E-PS-25-035
dism, presented with bilateral testicular swelling for a week. The patient A rare lesion of the kidney: epidermoid cyst
underwent bilateral testis-sparing orchiectomy. S.Y. Celik1, O. Ilhan Celik1, M. Cetinkaya2, Y. Dere1, H. Sahin2
1
Results: On microscopic examination of the right testis, the tumour Mugla Sitki Kocman University, Faculty of Medicine, Department of
was arranged in a diffuse, sheet-like pattern interrupted by fibrous Pathology, Turkey, 2 Mugla Sitki Kocman University, Faculty of
septa containing lymphocytes. Tumour cells had uniform, Medicine, Department of Urology, Turkey
h y p e r c h r o m a t i c n u c l e i a n d l a rg e , c l e a r c y t o p l a s m . T h e
immunoprofile of this tumour showed diffuse positive staining for Background & Objectives: Epidermoid Cyst of renal pelvis (ECRP)
CD117, PLAP and OCT4. These findings were consistent with is a rare benign entity. The possible histogenetic mechanisms of
seminoma. Intratubular germ cell neoplasia was detected. On micro- ECRP are debated to be the epidermal remnants of Wolffian duct,
scopic examination of the left testis, the tumour included two differ- squamous metaplasia after chronic irritation with urinary stone and
ent components. The first and the relatively more common compo- traumatic implantation of epithelium during external
nent (%90) was composed of cohesive, anaplastic epithelial cells in manipulation.The symptoms depend upon the associated disease or
glandular patterns. The immunoprofile of this component showed size of the cyst.
diffuse staining for CD30 and OCT4. The other component (%10) Methods: A 55-year-old man was referred to Urology clinic because of
comprised generally solid and occasionally duct-like formations. severe pain in his right waist and hematuria. The ultrasound examination
Tumour cells had vesicular nuclei and scanty cytoplasm. This com- showed partial enlargement of right kidney, dilatation of pelvicaliceal
ponent showed positive staining for glypican3 and AFP, negative system, hydronephrosis and staghorn type calculus in pelvicaliceal region
staining for OCT4. These findings were consistent with mixed affecting upper pole of the kidney. Also, there was a simple cortical cyst
TGCT (%90 embryonal carcinoma and %10 yolk sac tumour). with a diameter of 5cm.
Conclusion: Bilateral TGCTs can be metachronous or synchronous. Results: Partial nefrectomy preserving the lower pole was performed and
Most bilateral TGCTs are seen as metachronously and they are generally the histopathologic diagnoses were chronic pyelonephritis, lipomatosis,
 Virchows Arch

lithiasis and a cystic lesion which had a wall comprising of mature squa- Results: The patient presented with intermittent gross hematuria.
mous epithelium with granular layer and the lumen full of compact Cystoscopy revealed a polypoid solid mass. Transurethral resection
lamellated keratinous material. All of the material was microscopically was performed and subsequent local chemotherapy by Mitomycin
examined, and no atypia, dysplasia or carcinoma was identified. The cyst followed. The patient underwent cystoscopic resection twice in a
was diagnosed as Epidermoid cyst. year. Histopathological examination revealed classic papillary
Conclusion: Epidermoid cyst is a very common lesion of the skin; urothelial carcinoma morphology with lamina propria invasion.
however, ECRP is extremely rare. The treatment of it is surgical Additionally, numerous signet-ring cells were present in some parts.
excision. No recurrence, lymph-node and distant metastasis were Mucinous or glandular differentiation was not seen any part of the
considered. The importance of this lesion is that it may mimic tumour.
malignancy on radiologic examination and thus may lead to un- Conclusion: Urothelial carcinoma has several variant morphologies.
necessary nephrectomy. Better clinical awareness of the entity and Approximately 20% of urothelial carcinomas contain areas of squamous
a preoperative biopsy may preserve the kidney. or glandular differentiation, occasionally signet ring cells may be present.
Determining of these variants is very important in the staging, treatment,
prognosis.
E-PS-25-036
Sporadic renal hemangioblastoma: report of a case and review of the
literature E-PS-25-038
R. Amorim1, C. Fleming2, M. Oliveira2, L. Brochado Ferreira1, N. Primary Seminal Vesicle Adenocarcinoma (PSVA): the critical role of
Lamas1, B. Fernandes1, J.R. Brandão1, A. Coelho2, J.R. Vizcaíno2 morphology in a rare neoplasm
1
Centro Hospitalar e Universitario do Porto, Portugal, 2 Anatomical L.L. Sousa Veras1, S.R. Morini da Silva1, N. Soares de Menezes2,1
1
Pathology Service, Department of Pathology, Hospital and University Barretos Cancer Hospital, Brazil, 2 European Society of Pathology,
Center of Porto, Porto, Portugal Brazil

Background & Objectives: Hemangioblastoma is a rare benign tumour Background & Objectives: A 77-year-old male with rectal pain, hema-
which is known to occur in association with von Hippel-Lindau disease turia and weight loss in the last five years. Biochemical tests: PSA 2.73
(VHL) in approximately 25% of cases. Occurrence outside the central ng/ml and CEA 1.59 ng/ml. MRI showed an expansile, lobulated, solid-
nervous system (CNS) is exceptionally rare. We describe a case of spo- cystic and haemorrhagic mass (13.8 X 5.7 X 3.2cm), located superiorly to
radic renal hemangioblastoma with a review of the literature in order to the prostate. The lesion had an intimate contact with the ejaculatory duct.
determine the typical immunological and morphological profile of Bladder, rectum and prostate were normal. The mass was resected with
hemangioblastomas arising outside the CNS. lymphadenectomy. This case report intends to present an exceedingly rare
Methods: A 62-year-old man presented with abdominal pain and an neoplasm of the GU tract.
abdominal ultrasound scan revealed a lower pole renal tumour. CT con- Methods: Grossly, the lesion was regular, lobulated, with smooth surface
firmed the tumour and the appearances were highly suspicious for renal measuring 10.0 x 8.5 x 3.0cm. The sections demonstrated cystic areas
cell carcinoma. A partial nephrectomy was performed, and a subcutane- filled with a central and dense brownish or blackened material, with a
ous nodular lesion suspected of metastasis was also resected. polypoid appearance and thick white walls. Microscopically, it was an
Results: Histologically, the renal tumour was composed of rounded epithelial neoplasm, with a predominant papillary architeture and
or polygonal cells with pale cytoplasm and small bland central nu- scattered glandular structures. The cells had round, large, clear nuclei,
clei. Many of these cells have microvacuolated cytoplasm. There are prominent nucleoli and sparse eosinophilic cytoplasm. Extensive areas
numerous small capillary-sized stromal blood vessels. of necrosis and desmoplasia were observed and two lymph nodes were
Immunohistochemically, renal tumour cells showed diffuse expres- positive.
sion for inhibin-alpha, S-100 protein, vimentin and only the vascu- Results: Morphological findings associated with the immunohisto-
lar endothelial cells expressed CD34. A renal hemangioblastoma chemical profile (positivity for CK7, CA-125 and negativity for
was diagnosed. The separately excised soft tissue lesion showed CK20, PSA, GATA 3, RCC, Thyroglobulin, Prostein, p53, WT1
characteristic cytoarchitectural features of a spindle cell lipoma, and SALL4), clinical and radiological history and exclusion of neo-
fat-free variant. plasms in other sites such as bladder, prostate and rectum confirm
Conclusion: To the best of our knowledge, 31 cases of primary the diagnosis of PSVA. PSVA is a rare tumour, with about 60 cases
hemangioblastoma of the kidney have been reported, and little is known reported to date. The etiology may be related to testosterone stimu-
about their clinicopathologic features. The differential diagnosis of lation. The main differential diagnosis is secondary infiltration of
hemangioblastomas includes several benign and malignant entities. the seminal vesicle.
Careful morphological examination and immunohistochemical evalua- Conclusion: According to Dalgaard e Giertson (1956) the required
tion are crucial for correct categorization of these neoplasms. Regarding criteria for the diagnosis of PSVA are: the tumour must be a carcinoma
the concomitant subcutaneous lesion, there is no relationship between located exclusively or mainly in the seminal vesicle; the exclusion of
these tumour types. another primary carcinoma is mandatory and the tumour must be prefer-
entially a papillary adenocarcinoma. The prognosis is poor with survival
E-PS-25-037 usually less than 3 years.
Urotelial carcinoma of the bladder with signet ring cells: a case Program of Assistance and Incentive to the Researcher (PAIP) - Pio XII
report Foundation, Barretos, SP
A. Ok Atilgan1, E. Yilmaz Akcay1
1
Baskent University Faculty of Medicine Pathology Departmant, Turkey
E-PS-25-039
Background & Objectives: The presence of numerous signet ring cell Histochemical techniques applied in freezing cuts during intraoper-
without any type of adenocarcinoma cells originating in papillary ative biopsies in a renal transplantation
urothelial carcinoma is very rare. A. Salazar Nicolas1, M.I. Ortuño Moreno1, L. Barona Garcia1, A.
Methods: We report a case of 58-year-old male with invasive papillary Caballero Illanes1, N. Villa Lorente2, M.A. Menárguez Arnaldos3, M.D.
urothelial carcinoma of the urinary bladder with signet ring cell differen- Perez Caparros4, G. Ruiz Garcia1, M.I. Oviedo Ramirez5, E. Martinez
tiation, without glandular differentiation Barba1
Virchows Arch

1
Servicio de Anatomía Patológica, Hospital Clínico Universitario Virgen typical dual BSPRCC morphology, with prominent cytophagocytosis/
de la Arrixaca, Spain, 2 Servicio de Anestesia y Reanimación, Hospital emperipolesis. We observed diffuse positivity for Cam5.2/CK7/CK903/
Clínico Universitario Virgen de la Arrixaca, Spain, 3 Servicio de Vimentin/Racemase, focal positivity for CD15/CD10 and negativity for
Urgencias. Hospital Clínico Universitario Virgen de la Arrixaca, Spain, CK20/CD117/HMB45/Melan-A. Cyclin-D1 was positive exclusively in
4
Servicio de Ginecología y Obstetricia, Hospital de Mèrida, Spain, squamoid areas. Gains of chromosomes 7/17 were detected. The hilar
5
Servicio de Anatomía Patológica, Hospital Clínico Universitario metastasis exhibited solid/papillary growth pattern.
Virgen de la Arrixaca, Spain Conclusion: Recognizing BSPRCC as a distinct variant of PRCC is
important, as published data suggest it may present aggressive behaviour
Background & Objectives: The introduction of more extended clin- and metastatic potential. However, given the low number of reported
ical criteria when considering the suitability of a donor has led to an cases, the prognosis is still hard to predict. In our case, 11-months after
increase in the number of transplants, especially kidney transplants, surgery the patient is alive with no evidence of disease.
and this implies a rise in intraoperative biopsies performed in the
pathology department. Given this growth in transplants from “not
ideal donors“ makes the histological study should be more precise, E-PS-25-041
optimal and objective. Lymphoepithelioma-like carcinoma of the bladder: a case report
Methods: 18 cases about intraoperative renal transplant biopsy between O. Semerci1, O. Okcu1, M.Y. Akar1
1
the months of December and January of 2018-2019 were studied. The Recep Tayyip Erdogan University, Department of Pathology, Turkey
samples were stained with Hematoxylin-Eosin and Chromotrope Aniline
Blue was applied to enhance fibrosis. The results obtained in techniques Background & Objectives: Lymphoepithelioma-like variant of the blad-
were compared each other. der carcinoma is an infrequent variant of urothelial carcinoma that micro-
Results: In the study about glomerular fibrosis comparing Hematoxylin- scopically mimics lymphoepithelioma of the nasopharynx. It has been
Eosin and Chromotrope Aniline Blue stainings, 5 cases showed a greater recently described entity and it is recognized in the WHO classification
lesion in their study with Aniline (27.7%), 3 cases with a diagnosis of as a variant of urothelial carcinoma. Most patients are elderly male. We
lesion of lesser degree (22.3%) and 11 showed similar lesions between aimed to present this rare case with microscopic and immunohistochem-
HE and Aniline (50%). Regarding the study about interstitial fibrosis, 5 ical features
cases presented a greater lesion with the Sudan technique (27.8%), 2 Methods: We report a case of a 72-year old male who presented to our
cases with lesion of lesser degree (11.1%) and 11 showed a similar lesion hospital with hematuria. The clinical impression was consistent with a bladder
(61.1). %). tumour. Transurethral-resection of the bladder tumour was performed.
Conclusion: The introduction of Chromotrope Aniline Blue techniques Results: In microscopic examination tumoral infiltration composed of
in the intraoperative study of liver transplantation allows a more objective cords and sheets of undifferentiated appearing cells with large nuclei
and sensitive study to detect possible organic alterations. These specific and prominent nucleoli observed in the lamina propria. Cytoplasmic bor-
techniques enhance the fibrous lesions that we must study and their ap- ders were indistinct giving the tumour syncytial appearance. A prominent
plication does not significantly increase the time of histological study. In and dense mix type inflammatory cell was present at the background.
case of diagnostic doubt these techniques can offer a more reliable diag- There was an accompanying focal non-invasive urothelial carcinom at
nosis. neighboring epithelium. The invasive component of the tumour was
showing purely lymphoepithelioma-like morphology. Immunohisto-
Supported by Servicio Murciano de Salud de la Región de Murcia. chemically the tumour cells were strongly positive for panCK, CK7 and
weakly positive for GATA3 and negative for p63. Inflammatory cells in
the background were positive for CD3, CD20 and CD68. Based on the
E-PS-25-040 morphological examination and immunohistochemical features the diag-
Biphasic Squamoid Papillary Renal Cell Carcinoma with metastatic nosis of lymphoepithelioma-like urothelial carcinoma was made. The
involvement - case report of a rare entity and literature review patient received intravesical BCG treatment. After a 1 month follow up
S. Lopes Petronilho1, M. Cantante1, J. Vieira2, R. Vieira1, A. Rodrigues1 a re-transurethral resection performed and no residual tumour was detect-
1
Pathology Department, IPO-Porto, Portugal, 2 Genetics Department, ed in the specimen.
IPO-Porto, Portugal Conclusion: Lymphoepithelioma-like variant of the urothelial carcinoma
is a rare tumour. A proper morphological and immunohistochemical eval-
Background & Objectives: Biphasic Squamoid Papillary Renal Cell uation is needed to avoid diagnostic pitfalls because histological features
Carcinoma (BSPRCC), is a recently described entity, thought to may mimic other tumours such as poorly differentiated urothelial carci-
represent a rare variant of Papillary Renal Cell Carcinoma(PRCC). noma, poorly differentiated squamous cell carcinoma or lymphoma.
BSPRCC is morphologically characterised by 2 populations ar- Some reports confirmed favorable prognosis when it is pure. Our case
ranged in organoid structures, containing small, low-grade cells lin- is also responded well to chemotherapy treatment. We believe this respon-
ing alveolar-like structures, and central compact nests of larger siveness is related to lymphoepithelioma-like morphology of the invasive
squamoid-cells with vesicular nuclei and ample cytoplasm. Since tumour. It is crucial to report whether these cases are pure or have con-
the 1streport (2013) only ~100 cases were described. We report a current other carcinomas. The patient does well and has no recurrence
BSPRCC case with classical PRCC areas and metastatic spread. after 5 months of initial diagnosis.
Methods: 62-year-old female, with incidentally found 5cm solid/
expansile nodule associated with hilum adenomegalies, who underwent
radical nephrectomy and lymphadenectomy. Macroscopically, we found E-PS-25-042
an intraparenchymal expansile, pseudocapsulated, solid Succinate-dehydrogenase deficient renal cell carcinoma: a case study
nodule(size:4,5x4,2x3,5cm), with heterogeneous, firm/whitish-yellow D. Koumoundourou1, V. Tzelepi1, D. Mpantouna1, P. Ravazoula1, M.
and tan/friable cut surface and extensive hemorrhage and necrosis. A Melachrinou1
1
tumour nodule was identified in the lymphadenectomy specimen. University Hospital of Patras, Greece
Results: The tumour nodule comprised two distinct areas. The predom-
inant (90%) was characteristic of classical-PRCC, composed of papillae Background & Objectives: Succinate-dehydrogonase is an enzyme
covered by cells with pale cytoplasm and predominantly low-grade nu- of the mitochondrial complex whose germ line mutations are re-
clei, extensive hemorrhage and necrotic foci. The remaining (10%) had lated with familial pheochromocytomas/paragangliomas, GISTs,
 Virchows Arch

and less frequently, renal cell carcinomas with distinct histological Clinic, Bosnia and Herzegovina
and immunohistochemical features. We present a case of a renal
cell carcinoma correlating with succinate-dehydrogonase Background & Objectives: Bladder cancer is common cancer world-
deficiency. wide, with three to four times higher incidence in males than females.
Methods: A 49 years-old woman referred to our hospital because of urine Intravesical administration of bacillus Calmette-Guérin (BCG) immuno-
bleeding and left vague flank pain. CT revealed a left kidney mass mea- therapy, after transurethral tumour resection, is considered the gold stan-
suring 17cm in greatest diameter. Macroscopically the kidney was totally dard in treatment for superficial high-grade non–muscle-invasive bladder
replaced by a well circumscribed mass 16 cm in greatest diameter, with cancer
pushing margins, a tan brown surface and soft consistency. The mass was Methods: We report two cases of post –treatment BCG complications
confined to the kidney with no macroscopic invasion of the renal fat or that presented as granulomatous orchi-epidydimitis, and granulomatous
sinuses. Microscopically the neoplasm was composed of tubules lined by nephritis.
low cuboidal cells with smooth nuclear contours and abundant eosino- Results: A 69-years old male previously treated with intravesical BCG for
philic cytoplasm with eosinophilic vacuoles. Another distinctive feature superficial high grade bladder cancer presented with disuria, scrotal edema
was the presence of entrapped benign tubules as well as small numbers of and pain in groins. Ultrasound revealed a hypoechoic, solid mass. Patient
endotumoral mast cells. underwent left orchidectomy. Microscopic examination revealed a necro-
Results: Immunohistochemically the tumour cells expressed EMA, tizing granulomatous inflammation. An 79 years old man treated with BCG
P504S and PAX-8 with loss of Immunohistochemical staining for SDH for high grade bladder cancer presented asymptomatic for regular follow up
in tumour cells, and positive expression in the adjacent renal parenchyma. after completion of BCG treatment. Ultrasound and CT revealed moth-bite
Based on the microscopy and the immunohistochemical findings the like changes in the right kidney, not seen on previous imaging evaluations.
diagnosis was that of a succinate-dehydrogonase-deficient renal cell Patient was subjected to core needle biopsy and, at the same time, urin
carcinoma sample was obtained for mycobacterial culture on Löwenstein-Jensen me-
Conclusion: Succinate-dehydrogonase-deficient renal cell carcinomas dium, which resulted negative. Histopathological analysis showed necro-
are rare neoplasms with indolent biologic behavior. Their molecular ab- tizing granulomatous inflammation.
normality is double hit inactivation of one of the SDH genes. Genetic Conclusion: The etiology of granulomatous inflammation is broad and
testing and long term follow up for early detection of other succinate- expands over many etiologies including infectious, autoimmune, toxic,
dehydrogonase-related noplasms are always necessary (even in patients allergic, and neoplastic. Despite its weakened state, BCG has the potential
with absence of germ-line mutations). to cause local and systemic complications in treated patients. Knowledge
of prior BCG therapy and awareness of the potential related complica-
tions are essential for making the correct diagnosis prospectively and
E-PS-25-044 guiding appropriate treatment without delay.
Thyroid-like follicular carcinoma of the kidney: a case report
F. Kaya1, H. Kacar1, M.F. Acikalin1, B. Baseskioglu2
1
Eskisehir Osmangazi University, Department of Pathology, Turkey, E-PS-25-046
2
Eskisehir Osmangazi University, Faculty of Medicine, Department of Granulomatous vasculitis in testis associated with seminoma
Urology, Turkey D. Pouloudi1, A.C. Lazaris1, G. Liapis1
1
First Department of Pathology, Medical School, National and
Background & Objectives: Thyroid-like follicular carcinoma of the kid- Kapodistrian University of Athens, Athens, Greece
ney is a rare variant of renal cell carcinoma with a morphology that
closely resembles well-differentiated thyroid follicular neoplasms. It is a Background & Objectives: Granulomatous reaction in testicular
newly emerging histological variant of renal cell carcinoma, but it is not seminoma is a rather common finding encountered in up to 50% of the
included in the 2016 World Health Organization classification of renal cases. In contrast, granulomatous vasculitis as accompanying
tumours. Only 42 cases reported in the literature to date. paraneoplastic lesion is exceptionally rare. Herein, we report a case of
Methods: A 26 year-old-woman presented with a complaint of pain on granulomatous testicular vasculitis in association with seminoma.
right side, under back ribs. Physical examination was normal. The com- Methods: A 43-year-old man was admitted to the Hospital due to a
puted tomography (CT) scan showed a 38x37 mm, well-circumscribed palpable painless mass in the right scrotum. Imaging examination con-
lesion in the mid portion of her right kidney. A partial nephrectomy was firmed the presence of a testicular tumour and a radical right orchiectomy
performed. was performed.
Results: Macroscopically, the partial nephrectomy specimen demonstrat- Results: Cross sections revealed a whitish tumour measuring 4.5 cm in
ed a 39x38x34 mm, well-circumscribed, gray-yellow, gray-brown lesion. largest diameter. Histologically, the tumour was a classic seminoma ac-
Microscopically, the tumour was characterised by a notable follicular companied by very dense lymphoid infiltrates, as well as by granuloma
architecture composed of macrofollicles and microfollicles filled with formations. In addition, a limited number of small and medium sized
colloid-like material. The follicles were lined by cuboidal cells with round veins and lymph vessels, particularly in the hilum of testis, showed gran-
to ovoid nuclei. Staining for thyroid transcription factor (TTF-1) and ulomas within the wall, partially protruding into the lumens, while a
thyroglobulin were both negative. larger number of veins showed focal or diffuse lymphocytic venulitis.
Conclusion: Because this tumour shows similar histology to thyroid No ANCAs were detected in the serum, nor other systemic manifestations
follicular carcinoma, it is very important to exclude metastatic carcinoma of vasculitis were observed.
from the thyroid. A correct histopathologic diagnosis is crucial for appro- Conclusion: We report a rare case of granulomatous vasculitis of the test
priate treatment. is associated with seminoma. The absence of underlying immunological
disorder suggestive of systemic or organ-limited vasculitis favours tu-
mour antigens-related granulomatous reaction in vessel walls. Our find-
E-PS-25-045 ings expand the spectrum of granulomatous vasculitis.
Granulomatous inflammation after intravesical BCG immunothera-
py for bladder cancer
A. Chikha1, N. Ibisevic1, F. Skenderi1, S. Bajramovic2 E-PS-25-047
1
University Clinical Center of Sarajevo, Pathology Department, Bosnia Clear cell renal cell carcinoma with a distinct hemangioblastoma-like
and Herzegovina, 2 University Clinical Center of Sarajevo, Urology component: case report and review of literature
Virchows Arch

N. Castrejon1, A. Nadal2, I. Archilla3, L. Izquierdo4, A. Sierra4, L. contained clusters of clear cells similar to those of the border.
Buñesch5, M. Sole6, S. Diaz-Mercedes1 Immunohistochemically, the tumour cells were positive for keratin and
1
Pathology Department, Biomedical Diagnostic Center (CDB), Hospital negative for CD 68 in 2 cases. The treatment was surgical in all cases. No
Clinic of Barcelona, Spain, 2 Pathology Department, Biomedical tumour recurrence or metastasis was found in a mean follow up period of
Diagnostic Center (CDB), Hospital Clinic de Barcelona, IDIBAPS, 18 months.
Barcelona Spain, 3 Pathology Department, Hospital Clinic. University Conclusion: The MCRCC is a rare variant of RCC. It is a tumour with
of Barcelona, Spain, 4 Clinical Institute of Nephrology and Urology low malignancy potential and excellent prognosis.
(ICNU), Hospital Clinic de Barcelona, Spain, 5 Radiology Department
(CDI), Hospital Clinic de Barcelona, Spain, 6 Pathology Department,
Biomedical Diagnostic Center (CDB), Hospital Clinic de Barcelona, E-PS-25-049
Spain Pagetoid spread of urothelial carcinoma to the glans penis. A case
report
Background & Objectives: Diagnosis of renal cell carcinoma is chal- A. Simoulis1, A. Almorched1
1
lenging in cases with uncharacteristic histology. Recently it has been Pathology department, Skåne University Hospital, Malmö, Sweden
described clear cell renal cell carcinomas (CcRCC) with an
hemangioblastoma-like morphology. Few cases have been reported Background & Objectives: We report the case of the pagetoid spread of
showing an unusual immunoprofile and an unknown prognostic. Our urothelial carcinoma to the glans penis, eleven years after the initial pre-
aim is to describe a case of a metastatic CcRCC with sentation of the urothelial cancer and five years after the cystectomy. A
hemangioblastoma-like features. few cases of the same entity, usually under the term extramammary
Methods: 73 years-old man with a solitary kidney, transplanted due to Paget's disease secondary to urothelial cancer, is being described in the
chronic renal insufficiency. After 22 years he developed a tumour in the literature.
transplanted kidney. Biopsy was performed with the diagnosis of CcRCC, Methods: A 58 years old gentleman presented with an erythematous
low nuclear grade. Two years follow-up revealed a second tumour in the l e s i o n a r o u n d t h e u ri n ar y m e a t u s . A b i o p s y p e r f o r me d .
native kidney. He underwent nephrectomy and transplantectomy. Microscopically a pagetoid distribution of atypical cells in the squa-
Tumours were analysed histologically and immunohistochemically. mous epithelium was seen. A minimal panel of stains was applied.
Genotyping Polymerase Chain Reaction (PCR) was performed. The tumour cells were positive for CK5D3 and CK7 and negative for
Results: Microscopically, tumours were constituted by sheets, trabeculae Melan A, S100, p16, and CEA. The diagnosis of Extramammary
and dilated tubules of low nuclear grade clear cells combined with areas Paget's disease proposed.
of cells with scarce cytoplasm in a rich capillary network. The CcRCC Results: The case discussed at the national conference for Penile Cancer.
cells were positive for CKAE1/AE3, CD10, PAX-8 and Vimentin, where- The possibility of a pagetoid spread of urothelial carcinoma emerged.
as the hemangioblastoma-like component expressed □-inhibin, NSE and Supplementary immunostains used. The tumour cells were positive to
S-100. CD34 underscored the rich vascular structures. Genotype of both CK20, GATA3 and Uroplakin II. This phenotype supports the urothelial
tumours showed the presence of donor alleles in native kidney tumour, origin of this cancer. Therefore, the diagnosis revised to Extramammary
demonstrating that the neoplastic cells corresponded to the donor. Last Paget's disease secondary to urothelial cancer. New biopsies confirmed
control showed no recurrence. the presence of urothelial CIS in the urethra.
Conclusion: CcRCC with hemangioblastoma-like features is a difficult Conclusion: Pathologists must be aware of the possibility of this entity in
diagnosis for the heterogeneous morphology and immunophenotype. penile material, especially when there is a history of urothelial malignan-
Clinical relevance and prognostic implications are unknown. We present cy in the background. A panel of immunostains, which include GATA3
a case with an aggressive behavior and metastasis to the native kidney. and Uroplakin II, can help to make the differential diagnosis between a
Further studies will be necessary to understand its biology. true Extramammary Paget's disease and a pagetoid spread of urothelial
carcinoma.

E-PS-25-048
Multilocular cystic renal cell neoplasm of low malignant potential: a E-PS-25-050
study of four cases Glomerulations, perineural invasion and muscinous fibroplasia.
M. Mellouli1, M. Zghal1, I. Bahri1, M. Walha1, T. Sallemi Boudawara1, L. How common are they as diagnostic criteria in prostatic adenocarci-
Ayadi1, N. Gouiaa1 noma? A morphologic study of 30 cases on prostatic core biopsies
1
Department of Pathology, Habib Bourguiba Hospital, Sfax, Tunisia K. Adoke1, S. Ahmed2, Y. Iliyasu2, F. Mohammed2
1
Federal Medical Centre Birnin Kebbi, Nigeria, 2 Ahmadu Bello
Background & Objectives: Multilocular cystic renal cell carcinoma University Zaria Nigeria, Nigeria
(MCRCC) is a distinct subtype of clear cell renal cell carcinoma
(RCC). It represents a rare variant of RCC (1 à 4 %). The aim of this Background & Objectives: Diagnosis of prostate cancer is based on
work is to analyse the clinicopathological, therapeutic and prognostic microscopic criteria. It relies on the combination of architectural and
aspects of this rare histological variant through 4 observations. cytological features. Cytomorphological features like lack of basal cells,
Methods: Four cases were identified as MCRCC at our institution from prominent nucleoli and infiltrative growth pattern are useful criteria for
2008 to 2017. Their clinical characteristics, treatment, pathological fea- diagnosis of prostatic adenocarcinoma. Pathognomonic features of pros-
tures and outcomes were retrospectively reviewed. All cases met the tatic cancer are glomerulations, perineural invasion and mucinous
WHO criteria defining MCRCC. fibroplasia. We review these three later features in 30 prostatic needle
Results: The patients included 2 women and 2 men. The ages ranged biopsies.
from 45 to 65 years (median age was 54). All tumours were solitary and Methods: Thirty cases of prostatic cancer were diagnosed over a
unilateral. Macroscopically, tumour size ranged from 3 to 5 cm. It three year period (2015-2017).Information were extracted from the
consisted of non-communicating cysts separated by thin septa. Solid areas patients case notes. Paraffin embedded tissue blocks were retrieved
or substantially discernible mural nodules were absent in all cases. from the departmental archives. Fresh H&E slides were prepared.
Histologically, single layer of cubical and flattened epithelial tumour cells Cytomorphological features were viewed under the microscope
were lined in the cysts; the nuclei were small and grade nuclear was low using low(x40) and high(x100) magnifications. Data was analysed
(grade1 in 3 cases). Necrosis and mitosis were absent. Fibrous septa using SPSS version 20.
 Virchows Arch

Results: A total of 30 patients were seen during the study period. The immunohistochemical stains confirmed our diagnosis. Tumour cells
The mean age was 67±11.7 years. There PSA ranges from 24- were positive to NKX3.1 and AMACR and negative to GATA3, p63, CK
115ng/dl. On cytomorphology, 18(60%) cases had perineural inva- 34 beta E12. We did not find acinar prostate adenocarcinoma at all.
sion, 6(20%) had glomerulation while, 1(3.3%) had mucinous Conclusion: Pure prostatic ductal adenocarcinoma is an uncommon form
fibroplasias. Five (16.7%) had none of these features, although ab- of prostatic carcinoma (0,2 – 0,4 % of prostate cancers). Pathologists and
sent of basal cells, necrosis and infiltrative growth pattern were urologists must be aware of this rare type of malignancy when they are
demonstrated. dealing with papillary neoplasms of the prostatic urethra.
Conclusion: Glomerulation and mucinous fibroplasias are infrequent di- Immunostains can help to support the diagnosis.
agnostic findings on needle biopsies.

E-PS-25-053
E-PS-25-051 Testicular neuroendocrine tumour: case report
Renal cell carcinoma with papillary architecture. Analysis of 8 cases H. Ozkayalar1, F. Dirilenoğlu1, A.U. Onder1, G. Mocan1
E. Fuentes Vaamonde1, A. Sanz Zorrilla1, M.T. González Serrano1, F. 1
Near East University Faculty of Medicine, Cyprus
Leiva-Cepas1, M.d.M. Moreno Rodríguez1
1
University Hospital "Reina Sofía", Spain Background & Objectives: Neuroendocrine tumours (NETs) consist of
a spectrum of malignancies that can arise from neuroendocrine cells
Background & Objectives: The second most common type of renal throughout the body. Among these tumours, 85% occur in the gastroin-
carcinoma is papillary carcinoma (it is the tumour that is most frequently testinal tract, mostly in the ileum and appendix. Testicular neuroendocrine
composed of papillae). However, the papillary architecture can be shown tumours (TNET) account for less than 1% of all testicular neoplasms.
in many other entities. So a wide differential diagnosis should be made, TNET appears to be a young man's cancer and they are associated with
since the biological behavior and its treatment can differ from one an excellent prognosis
another. Methods: A 42-year-old man had an asymptomatic, enlarged scrotum on
Methods: Eight renal cell carcinomas with papillary architecture the right side. Ultrasonography revealed a solid tumour, measuring
were selected. Tumours were evaluated morphologically, immuno 2,7x2,1x2,2cm in the right testis. Beta-human chorionic gonadotropin
histochemically and the differential diagnosis problems were stud- and alpha-feto protein lactate dehydrogenase levels were normal. Right
ied. Although they did not compose all the types of neoplasms radical orchidectomy was performed
that can show papillary pattern, they were the most frequently Results: Grossly, the orchiectomy specimen showed a 2,7 cm well
found in the histopathological study. circumscribed, yellow-tan solid mass. Histologically, the tumour cells
Results: One case of clear cell carcinoma, 3 of type 2 papillary carcino- which were arranged in insular, and trabecular patterns in a background
mas, one clear cell papillary renal cell carcinoma, two type 1 papillary of fibrous stroma; had abundant granular, eosinophilic cytoplasm and
carcinomas, one mixed clear cell carcinoma and papillary type 1 carcino- round to oval nuclei with a “salt and pepper” chromatin pattern.
ma and one carcinoid tumour are presented. Diagnostic problems were Immunostains for neuroendocrine markers (synaptophysin, and CD56)
solved with adequate sampling, immunohistochemistry and, in one case, were strongly positive. Teratomatous elements or other germ cell compo-
with FISH. nents were not identified. A diagnosis of TNET was confirmed.
Conclusion: Not all tumours with a papillary pattern correspond to a Conclusion: Primary TNETs are rare. They represent less than 1% of
renal papillary carcinoma. A thorough evaluation of all the cytological all testicular neoplasms. TNET appears to be a young age patients
and architectural characteristics of these tumours is required, not only but may occur in children as in the elderly. Most cases primary
papillary pattern and of other associated patterns, but also the stromal testicular neuroendocrine tumours have an excellent prognosis fol-
component. Up to about thirty neoplasms with papillary features are lowing orchiectomy
described, differentiated by their behavior and morphology.
Complementary tests, such as immunohistochemistry, FISH and others,
are necessary for its classification. E-PS-25-054
Collision tumour of squamous cell carcinoma and primary malig-
nant melanoma of the glans penis: a case report
E-PS-25-052 A. Simoulis1
1
Pure prostatic ductal adenocarcinoma mimicking a papillary Pathology department, Skåne University Hospital, Malmö, Sweden
urothelial carcinoma. A case report
A. Simoulis1 Background & Objectives: The most common penile malignancy is
1
Pathology department, Skåne University Hospital, Malmö, Sweden squamous cell cancer while the primary penile melanoma is a rare tumour.
About 220 cases of penile melanoma are described in the literature.
Background & Objectives: Ductal adenocarcinoma can be a mimicker We present an unusual case of a collision tumour of primary melanoma of
of the papillary urothelial carcinoma, both for urologists and pathologists. glans penis and penile squamous cell carcinoma.
The right diagnosis is critical as the two types of cancer have a different Methods: A 53-year-old gentleman appeared at the local hospital emer-
therapeutic approach. gency department because of very painful back pain. The clinical exam-
Methods: We discuss all the cases of invasive urothelial cancer of the ination revealed a suspect penile cancer. Computed tomography showed
Skåne region at the interdisciplinary cancer conference of our hospital. numerous metastases. The patient was remitted to our hospital and our
Therefore, we reviewed the glasses from the transurethral resection spec- urologists performed a partial penectomy. On gross examination, we ob-
imens of an 85-year-old gentleman. The initial diagnosis was benign served that almost the whole glans penis was darkly pigmented. We were
prostatic tissue and papillary urothelial cancer of the prostatic urethra with able to recognize a few whitish areas and some areas of ulceration.
invasion in lamina propria, pT1. Results: During the histological examination, we saw an extensive inva-
Results: We reviewed eleven HE slides from the transurethral resection sion of malign melanoma and an area of a well-differentiated invasive
material. Microscopically we saw cancer with the formation of papillary squamous cell cancer. The malign melanoma destroyed areas of squa-
fronds with pseudostratified epithelium. The tumour cells were tall and mous cell cancer. In addition, we observed a lentiginous proliferation of
columnar, with prominent nucleoli and many mitotic figures. We revised atypical melanocytes within the basal layer of squamous cell cancer and
the initial diagnosis to prostatic ductal adenocarcinoma (papillary form). at the remaining intact mucosa. The melanocytic component showed a
Virchows Arch

varying degree of pigmentation, with polygonal epithelial-like cells and showed a positive methylation score. Additional 11 patients exceeded the
spindle-shaped cells, growing in nests or densely packed aggregates. threshold but up to date they have not experienced any second manifes-
Conclusion: Primary penile melanoma is a rare type of penile malignan- tation. Among the remaining 26 negatives, only one developed a recur-
cy. We present a collision of malign melanoma with squamous cell can- rence. A positive score correlated with a worse locoregional control of
cer. The unusual characteristics of this case are that the malign melanoma disease (p<0.05).
actively destroyed the squamous cell cancer and that we recognized a Conclusion: The DNA methylation analysis of 13 genes can be a useful
lentiginous proliferation of moderately atypical melanocytes in the squa- non-invasive method to identify surgically treated OSCC patients at risk
mous cell cancer nests and the remaining squamous mucosa. of developing a second neoplasia.

E-PS-25-055 E-PS-25-057
Extramedullary plasmacytoma of the bladder: a case report Low-grade oncocytic kidney tumour with papillary features
A. Simoulis1, M. Ehinger2 N.E. Alkanat1, K. Kosemehmetoglu1
1 1
Pathology department, Skåne University Hospital, Malmö, Sweden, Hacettepe University Faculty of Medicine, Department of Pathology,
2
Department of Clinical Sciences, Pathology, Skane University Turkey
Hospital, Lund University, Lund, Sweden
Background & Objectives: “Oncocytic renal tumour” definition em-
Background & Objectives: A few cases of extramedullary braces various entities such as renal oncocytoma, chromophobe renal cell
plasmacytoma with involvement of the urinary bladder have been de- carcinoma (RCC), type 2 papillary RCC (including oncocytic papillary
scribed in the literature. We present a case of this rare entity. A 52 years RCC), and eosinophilic variant of clear cell RCC. In a recent study,
old man was under medical investigation due to a feeling of pain and Trpkov et al. defined a new tumour referred to as “low-grade oncocytic
pressure in the bladder area. Urologists performed a cystoscopy and they tumour of kidney”, characterised by a solid/nested morphology with re-
found two areas of abnormal but not papillary urothelium, 4 cm and markable low grade features, as well as CK7 positivity and CD117 neg-
0,7 cm in diameter. The initial clinical diagnosis was cystitis. Biopsies ativity. Papillary architecture is not a feature described in this new entity.
were taken from these areas. Here, we report a low grade oncocytic kidney tumour with papillary
Methods: Microscopically examination revealed a reactive but benign features.
urothelium. The lamina propria was rich in immune cells in a Methods: A 1,4 cm renal tumour was identified incidentally in a 57-year-
lichenoid–like pattern. Almost all of this population consisted of plasma old woman in an abdominal computed tomography. The patient
cells that were CD138. The cytoplasmic kappa/lambda ratio of CD138- underwent partial nephrectomy and specimen was sent to pathology de-
positive plasma cells showed kappa monoclonality. partment. Formalin-fixed, paraffin-embedded tissue was prepared from
Results: Monoclonal gene rearrangements of IGH and IGK were also the tumour. 4 μm slides were obtained from paraffin blocks and stained
detected with PCR Hematological work-up and bone marrow examina- for hematoxylin eosin for routine microscopic examination. 4 μm sec-
tion showed no signs of plasma cell neoplasia. The final diagnosis was tions were also stained for CK7, CD10, AMACR, vimentin, CD117
extramedullary plasmacytoma with involvement of the urinary bladder. and CA IX immunohistochemistry using Leica Bond-Max Autostainer.
The patient follows the appropriate therapy. Results: Partial nephrectomy revealed a well-circumscribed, solid, tan-
Conclusion: We report a case of a rare entity. The role of the brown coloured tumour with small cyst like areas. Microscopically, tumour
pathologist is crucial for the diagnosis because an extramedullary was composed of both solid and true papillary areas with delicate fibrovas-
plasmacytoma in the bladder can be clinically interpreted as cys- cular cores. Tumour cells had low-grade (grade 1-2) morphology with oval-
titis. round nuclei, small nucleoli and granular oncocytic cytoplasm. There was
no foamy histiocytes within the papillary cores. Immunhistochemically
tumour was diffusely positive for CK7 and focally positive for CD10, while
E-PS-25-056 AMACR, vimentin, CD117 and CA IX were all negative.
Primary renal pelvis mucinous adenocarcinoma Conclusion: This is the first report of low grade oncocytic kidney tumour
T. Muzashvili1, G. Burkadze1 showing prominent papillary features. Differential diagnosis clearly includ-
1
Tbilisi State Medical University, Georgia ed type 2 papillary RCC; however, absence of foamy histiocytes and
AMACR, Vimentin, CD10 negative immunophenotype were not consis-
Background & Objectives: Oral Squamous Cell Carcinoma (OSCC) tent with this diagnosis. Although well-formed papillae are not a morpho-
showed a significant risk to develop local recurrences or second logical feature of oncocytoma and chromophobe RCC, the diagnosis of our
primary tumours during follow-up. Recently, we developed a non- case was most consistent with “low-grade oncocytic tumour of kidney” and
invasive assay based on oral brushing and DNA methylation anal- delicate papillary formations could be a rare finding and expand the spec-
ysis to early detect OSCC. In the present study using this assay, we trum of morphological presentations in this recently described entity.
investigated the adjacent area of surgical resection in a series of
OSCC during follow-up for prognostic purposes.
Methods: 42 consecutive OSCC patients were sampled during routine E-PS-25-058
follow-up after 6 months from surgical treatment, brushing the regenera- Can the total PSA value predict the Gleason score before prostate
tive mucosa covering the region that underwent the surgical OSCC exci- biopsy?
sion. DNA methylation level of ZAP70, GP1BB, KIF1A, ITGA4, M. Asmae1, A. Douida2, H. El Fatemi2,3, J.E. El Ammari4
1
LINC00599, MIR193, MIR296, TERT, LRRTM1, NTM, EPHX3, FLI1 University Hospital Center Hassan II of Fez, Morocco, 2 Department of
and PARP15 was evaluated by quantitative Bisulfite-NGS. After calcu- Pathology, Hassan II University Hospital, Fez, Morocco, 3 Faculty of
lating a score by Linear-Discriminant-Analysis, the samples were dichot- Medicine and Pharmacy of Fez, Morocco, 4 Department of Urology,
omized using a predefined threshold previously developed for early di- Hassan II University Hospital, Fez, Morocco
agnosis. One-Way-ANOVA and Kaplan-Meier curves served to evaluate
any significant difference between patients who experienced a second Background & Objectives: Prostate cancer is the most common malig-
neoplastic manifestation and the group who did not. nancy in men. Our objective is to determine if there is a correlation
Results: 6/42 (14,3%) patients developed a second neoplastic manifesta- between Gleason score and total prostate specific antigen (PSAt) in pa-
tion during follow-up period (mean follow-up: 14.3 months), of which 5 tients newly diagnosed with prostate carcinoma.
 Virchows Arch

Methods: We retrospectively reviewed the data of 73 men who were diag- Methods: We retrospectively reviewed the data of 73 men who were diag-
nosed with prostate cancer between 2012 and 2017, within the departments of nosed with prostate cancer between 2012 and 2017, within the departments of
urology and pathology at the Hassan II university hospital center. We record- urology and pathology at the Hassan II university hospital center. We record-
ed Patients’ age, prostate-specific antigen levels at diagnosis, prostate biopsy ed Patients’ age, prostate-specific antigen levels at diagnosis, and prostate
and radical prostatectomy specimen Gleason scores. biopsy and radical prostatectomy specimen Gleason scores.
Results: The mean age of our patients was 69.60 years (52-98), the mean Results: The mean age of our patients was 69.60 years (52-98), the mean
prostate specific antigen level was 258.27 ng/mL (5 - 3330 ng/mL). The mean prostate specific antigen level was 258.27 ng/mL (5 - 3330 ng/mL).
Gleason score was 7.1, 38.35% of patients were graded group 1; 12.33% Adenocarcinoma was the histological type in 100% of our cases. The mean
group 2; 8.22% group 3; 15.07% group 4 and 26.03% were graded group 5. Gleason score was 7.1, 38.35% of patients were graded group 1; 12.33%
Adenocarcinoma was the histological type in 100% of our cases. group 2; 8.22% group 3; 15.07% group 4 and 26.03% were graded group 5.
Prostatectomy was performed in 38.4% patients. In our study, the PSA level Prostatectomy was performed in 38.4% patients. The biopsy Gleason score
and the biopsy Gleason score were higher in patients with bone metastases. and the prostatectomy Gleason score were correlated in 48%, upgraded in
However, there was no statistical significant correlation between PSA level 48%, and downgraded in 4% of cases with a correlation coefficient of 0.69.
and the Gleason score (correlation coefficient = 0,30). Conclusion: Gleason score is the most important parameter in prostate
Conclusion: Gleason score is the most important parameter in prostate can- cancer. This study has permitted to obtain results that are closely similar
cer. According to our study, there is no relationship between Gleason score to the result cited in the literature.
and PSAt level. The obtained results are not similar to those cited in the
literature. This is probably due to the restricted number of our cases.
E-PS-25-061
Paratesticular angiolipoma: an unusual entity involving in the
E-PS-25-059 paratesticular region
Low-grade oncocytic renal tumour (CD117-negative, cytokeratin 7- R. Ayadi1, F. Gargouri1, N. Mansouri1, I. Msakni1, A. Bouziani1, B. Laabidi1
1
positive): a new entity? Report of four new cases Pathology Department, Military Hospital, University of Tunis El Manar,
M. Muñoz Martín1, C. Gómez-de María2, M. Pèrez-Expósito2, A. Faculty of Medicine of Tunis, Tunisia.
Serantes1, R. Morellón1, P. San Miguel1, J. Ortiz-Rey1
1
Hospital Álvaro Cunqueiro, Spain, 2 Povisa, Spain Background & Objectives: Angiolipomas (AGLs) are not uncommon
tumours of the soft tissue, but are rarely found in other parts of the body
Background & Objectives: Low-grade Oncocytic Renal Tumour such as the breast, gastrointestinal tract, thyroid, bone and oral cavity.
(LORT) CD117-negative and Cytokeratin 7-positive, has been recently Intrascrotal angiolipomas (AGLPs) are an uncommon paratesticular tu-
proposed as an emerging/provisional entity different from oncocytoma, mour that has seldom been reported in the literature.
eosinophilic chromophobe renal cell carcinoma (ChRCC) and hybrid We aimed to report a new case of AGLP and to describe its histopatho-
oncocytic tumour. logical features
Methods: We have reviewed 64 surgical specimens diagnosed as Methods: A 21-year old man presented a large scrotal mass of approxi-
ChRCC, searching for features of LORT. mately 2-years duration. He was managed conservatively untill he report-
Results: Five LORTs (7,8% of the ChRCCs) were identified. One previously ed a testicular hypotrophy. The patient had no history of pelvic surgery or
reported is excluded from this communication. The other four affected 3 testicular trauma. Clinical examination revealed an approximately 21 mm
women and 1 man, aged 69-83 years. Two were in the right and two in the scrotal mass. Ultra-sonography showed a solid mass with microcalcifica-
left kidney. Tumour size was 6, 2, 6,5 and 3,5 cm. Histologically, they were tion. An orchidectomy was performed.
well delimitated unencapsulated tumours, with a compact nested, focally Results: On gross examination, mean size, of the specimen, was 3,5cm. Cut
tubular, architecture. The cells had oncocytic cytoplasm and round to oval section showed a well-circumscribed reddich-brown paratesticular mass mea-
nuclei. Nucleolar grade would be 2. Only focal perinuclear clearing was seen. suring 15mm with focal areas of hemorrhage.The histological examination
One case showed focal necrosis. Immunohistochemistry: Positive for CK7, showed a tumour composed of mature adipocytes surrounded by thin-walled
cadherin E, EMA and SDHB; and negative for CD117, CD10, vimentin, capillaries and fibrin microthrombi found in blood vessel lumens. Based on
CA9 and CK20. AMACR was negative in 2 cases and focal/faint positive these histologic findings, the final diagnosis of AGLP was considered.
in the other two. After a follow-up of 8 months - 7 years the patients are Conclusion: This case has unique features regarding its location and
alive and without relapse or metastases. diagnosis. AGLP are rare introscrotal masses but can grow slowly neces-
Conclusion: A subset of oncocytic tumours with the features described as sitating surgical incision. It has to be distinguished from aggressive
LORT could be recognised among our ChRCCs. Our cases have had a angiomyxoma and liposarcoma.
favourable evolution although follow-up has been short in three of them.
We report the first case of LORT with necrosis, whose impact on prog-
nosis remains to be established. Further studies of new cases are needed to E-PS-25-062
validate LORT as a new entity. Plasmocytoid urothelial carcinoma: an unusual and aggressive vari-
ant of urothelial carcinoma
A. Dhaoui1, K. Hamza1, D. Ben Ghachem1, K. Bellil1
1
E-PS-25-060 Forces de securite interieure, Tunisia
Gleason score correlation between prostate biopsy and radical pros-
tatectomy specimens Background & Objectives: Plasmacytoid urothelial carcinoma (PUC) is a
M. Asmae1, A. Douida2, H. El Fatemi2,3, J.E. Elammari4 variant of infiltrating urothelial carcinoma that is characterised by tumour
1
University Hospital Center Hassan II of Fez, Morocco, 2 Department of cells that have striking morphologic resemblance to and immunohisto-
Pathology, Hassan II University Hospital, Fez, Morocco, 3 Faculty of chemical overlap with plasma cells. It is an uncommon aggressive
Medecine and Pharmacy of Fez, Morocco, 4 Department of Uroology, urothelial carcinoma accounting for 1-5% of invasive urothelial carcinoma.
Hassan II University Hospital, Fez, Morocco Methods: We reported a case of bladder PUC in a 62 years-old man who
presented a recurrence of macroscopic hematuria after BCG intravesical
Background & Objectives: Prostate cancer is the most common malig- instillation.
nancy in men. In this study, we evaluated the correlation between biopsy Results: Transurethral resection of the bladder showed a high-grade tu-
Gleason scores and radical prostatectomy specimen scores. mour arranged in discohesive cords and plasmocytoid features without
Virchows Arch

1
penetrating the muscle and presented an urothelial papillary differentia- Inst. Umweltmedizin c/o ICSD/IAS e.V. Muenchen, Germany, 2 Amgen
tion in surface. Plasmocytoid morphology is a source of diagnostic di- Res. Munich (Exec. Dir.) & IUM c/o ICSD/IAS e.V., Germany, 3 St.
lemmas and amongst the differential diagnosis commun ones are cystits Elisabeth Univ., Bratislava, Slovakia, 4 Inst. Umweltmedizin c/o
with plasma cell infiltration, melanoma, plasmocytoma and rhabdomyo- ICSD/IAS e.V. Muenchen, Germany, 5 Univ. Muenchen and Free Univ.
sarcoma. The urothelial differentiation and positivity expression of Berlin, Med. Fak., Germany, 6 Univ.Muenchen, Klinikum Grosshadern
plasmocytoid cell for CD138 confirmed the diagnosis. (Dir.a.D.), Germany, 7 Univ. Muenchen Med. Fak., Premium Med. Clinic
Conclusion: Compared with conventional urothelial carcinoma, PUCs have (Dir.), Germany, 8 Univ. Innsbruck, School Educ. (Dean), Austria, 9 Univ.
greater chance for higher-stage disease, surgical margin positivity, and metas- Lxbg. and Vienna, Fac. Psychology (Dean), Austria, 10 Univ. Rostock,
tasis at presentation that translate into its poorer outcome. Because of its Inst. Physiology (Dir.a.D.), Germany
unfavorable behavior, a more aggressive management approach is being
recommended including the consideration for cystectomy in pT1 disease. Background & Objectives: Angiocardiac and neuro-pathology depends
That's why it must be distinguished from the other carcinoma variants. on nephrology. Reports on integrative genitourology&physiology are
given. Pathophysiology is underrepresented in pathology. Presently is
considered pyeloureter in context of an integrative pathology.
E-PS-25-066 Method: Motor activity (isotonic rec.), neurogenic contractions to
On electropathophysiology and ultrastructure of pyeloureter electrostimulation (nCES 10+100Hz,0.3ms,3s,5-30V) [3]. Electron-
M. Michailov1, E. Neu1, B. Rattel2, U. Welscher3, M. Wirth3, U. Härlin3, D. microscopy.
Martin3, H. Dahlheim4, J. Foltinova5, U. Matis6, G. Werner7, D.G. Weiss8 Results: A. Spontaneous phasic contractions (SPC): More than 10 SPC-
1
Inst. Umweltmedizin c/o ICSD/IAS e.V. Muenchen, Germany, 2 Amgen patterns (1-2/min) were observed in isolated pyelon/P & ureter/U of guinea-
Res. Munich (Exec. Dir.) & IUM c/o ICSD/IAS e.V., Germany, 3 Inst. pig/GP & human/H (n=242): Irr-®ular (frequency), non-&uniform (ampli-
Umweltmedizin c/o ICSD/IAS e.V. Muenchen, Germany, 4 Univ. tudes), burst-like, others were evident. B. Motor reactions after nCES: nCES
Muenchen, Inst. Physiol., Germany, 5 Univ. Bratislava, Med. Fac., induced only single contr. of U, but a temporary (1-3min) strong increase of
Slovakia, 6 Univ.Muenchen, Fac. Vet. Med., Chir. Clinic (Dir.a.D.), SPC of P from GP&H. TTX (1μg/ml) & hypothermia (25,15°C) antagonized
Germany, 7 Klinikum Darmstadt, Med. Clinic (Dir.), Germany, 8 Univ. this (neurogenic excitation). C. Pharmacological analysis: Adrenergic & cho-
Rostock, Inst. Physiology (Dir.a.D.), Germany linergic blocking agents inhibited P&U. D. Essential differences in motor
patterns of GP&H pyeloureter exist, e.g. burst-like contractions in H-prepa-
Background & Objectives: Despite enormous information about normal rations. E. Ultra-structure demonstrates essential differences between GP-H-
and pathological electrical&motor physiology of pyeloureter (P&U), also ureter, e.g. cell distance GP:40nm, H:200nm (magnification 10.000x, n=20).
reports about ultrastructure are essential open questions which are to be OPEN QUESTIONS: Role of various motor patterns for normal & patho-
discussed, supporting better therapy in genitourology. logical P&U function. Participation of excitatory & inhibitory non-
Method: Recording of electrical activity (intracellular) of P&U; cholinergic & non-adrenergic (co-)transmitters. Role of ultrastructure for path-
ultrastructure. ological motor patterns.
Results: Systematic observations about action potentials in guinea-pig dem- Conclusion: It is evident necessity of holistic & multidimensional re-
onstrate presence of very different electrical patterns – spikes/S, burst/B, burst- search in context of integrative pathology conc. pathophysiology and
plateaus/BP, etc. (n=63). They are dependent on ratio KCl:Ca Cl2 (5.6mmol/ pathomorphology of pyeloureter leading to better diagnosis and therapy
l:2.16mmol/l = 1:1), e.g. after 8:2 S are transformed into BP, similar to addition of renal diseases, supporting UNO-Agenda21 for better health, medical
of BaCl2. MgCl2 has only negative chronotropic effect. Recording of myocytes education, developing help, etc. on global level. Ref.: [1]-Pathology:
from human P&U is very difficult – action potentials are present (n=120). ESP-2018-Bilbao, Eur.J.Pathol. 473/Suppl.1:S180; ESP-2017-
Ultra-structural observations by electron microscopy demonstrate essential dif- A m s t e r d a m , Eu r. J . P a t h o l . 4 7 1 / S u p p l . 1 : S 2 4 5 / S 2 8 4 / S 3 0 7 ;
ferences between Guinea-pig/GP&human/H U, e.g. cell-distance GP:40nm, Int.Acad.Pathol./ESP-2016-Köln, Eur.J.Pathol. 469/Suppl.1:S245.
H:200nm (magnification 10.000x,n=20). Open questions: a. Correlation of [2]-SIU-2016-B-Aires (IntSocUrol) Abstr-Book/AB:136&223; 2011-
various electrical patterns with motor ones. What are normal&pathological Berlin-CongrUrol 78/S3A:S188/S385; 2007-Paris 70/S3A:232-3; 2004-
patterns? b. Importance of renin-angiotensin system and mechanosensitive Honolulu-BrJUrol 94:24-5/258-9/305. Physiology and Philosophy (see
ion channels for normal&pathological electrical&motor activities of P&U. c. Michailov et al. this congress)
Interaction between spontaneous phasic (SPC:1-5/min) and tonic contractions
(STC:0.1-0.2/min) after BaCl2 in relation to various electrical patterns
(cystotonometry in vitro). d. Importance of differences in ultrastructure for a-c. E-PS-25-068
Conclusion: Clarification of these questions could be of essential Prognostic role of pre-operative neutrophil - lymphocyte ratio (NLR)
importance for uro-pathology, incl. also for angiocardiac and neuro- in urothelial carcinoma: experience of tertiary center
hormonal pathology supporting UNO Agenda 21 for better health, K. Sahu1, M. R2, P. KS3, J. Kini1, F. Lobo2
1
medical education,ecology, economy,etc. on global level. Department of Pathology, Kasturba Medical College, Mangalore, India,
2
MAHE, India, 3 MAHE
Ref (see also Neu et al. this congress): [1]-IUPS-2017-Rio-de-Janeiro,
AB:No. 997/999/1001/1003; 2009-Kyoto, J.Physiol.Sci., 59/ Background & Objectives: Neutrophil-Lymphocyte ratio (NLR)
S1:168&214&447-8. FEPS-2018-London-Europhysiol AB:p334P- as an indicator of heightened systemic inflammatory response,
337P; 2014-Budapest, Acta Physiol. 211/s697:p62-64; 1999-Prague, predicts increased disease burden and poor oncological outcomes
PhysiolRes48/S5:138. DPG-2002-Tübingen, EurJPhysiol443/S1:S334. in urothelial carcinoma (UC). The study was undertaken with an
[2]-FISP-2018-Beijing (Philos.) No.1348-50/1374-5; 2013-Athens aim to evaluate the association of NLR with clinicopathological
AB:464-5&503-4&766. IAB-2018-India (Bioethics) AB:392&393; variables and survival outcomes.
2016-Edinburgh Proc93-95; 2008-Istria 290&307. Methods: A total of 80 patients of UC were enrolled in the current
retrospective study. Pre-operative NLR (within 1 month prior to
the procedure), patient age, sex, tumour grade, pathological stage,
E-PS-25-067 recurrence free survival (RFS), progression free survival (PFS)
On an integrative pathology of pyeloureter and cancer specific survival (CSS) were recorded. We chose a
E. Neu1, M. Michailov1, B. Rattel2, V. Foltin3, U. Welscher4, H.W. Bauer5, A. cut-off value 2.7 for NLR and patients were divided into two
Hofstetter6, E.R. Weissenbacher7, M. Schratz8, G. Weber9, D.G. Weiss10 groups (NLR<2.7 and ≥2.7).
 Virchows Arch

Results: NLR ≥2.7 was significantly associated with advanced tu- Background & Objectives: In the field of histopathology, a risk for
mour stage (p=0.001) but not with tumour grade (p=0.116). misdiagnosis is a serious issue. A standard way to visualise cell
Progression (p=0.032) and death rates (p=0.026) were high in pa- morphology is through H&E staining often combined with DAB
tients with NLR ≥2.7. Mean RFS (p=0.03), PFS (p=0.04) and CSS chromogenic stain. However, this method suffers from narrow dy-
(p=0.04) were reduced in patients with NLR ≥2.7. On univariate namic range, problems with quantitation and difficulties with
analysis, NLR ≥2.7 predicted worse RFS (HR= 2.928, P=0.007), multiplexing and co-localisation. Fluorescent IHC techniques gen-
PFS (HR=3.180, P=0.006) and CSS (HR=3.109, p=0.016). erate a more quantitative readout but suffer from photobleaching.
However, it was not an independent predictor of outcomes on mul- Here we present that the use of up-converting nanoparticles
tivariate analysis. (UCNPs) allows to overcome problems associated with commonly
Conclusion: Only tumour stage and grade are independent predic- used imaging techniques.
tors of RFS, PFS and CSS. High NLR at a cut-off value ≥ 2.7 is Methods: Novel luminescent UCNPs were used together with a
associated with advanced pathological stage, but does not have an prototype instrument to image selected markers, e.g. Her2, in the
independent predictive value for RFS, PFS and CSS. human tissue. Formalin-fixed paraffin-embedded human colon and
breast cancer tissues were sectioned and stained using autostainer.
UCNP fluorescence imaging of the human tissue sections was com-
E-PS-25-069 pared with a standard DAB based IHC. Pulsed excitation and gated
Paratesticular adenomatoid tumour: case report detection were explored to improve the scanning speed. UCNP and
A. Kilitci1, E. Erşekerci2 H&E co-staining and co-imaging were also investigated.
1
Ahi Evran University Medical Faculty, Dept of Pathology, Turkey, 2 Ahi Results: Images obtained with our novel device clearly show that
Evran University Medical Faculty Dept of Urology, Turkey developed by us antibody-UCNP conjugates can be used to success-
fully stain the human tissues. Brightfield images show that UCNPs
Background & Objectives: Adenomatoid tumour (AT) is a kind of are not visible in white light and hence do not interfere with stan-
specific and uncommon benign tumour of female and male genital dard tissue evaluation by a pathologist. Additionally, brightfield and
tracts. It is thought to arise from mesothelial cells. AT represents a luminescent images can be merged to provide better understanding
diagnostic challenge due to their clinicopathological signs similar of tissue morphology.
to those of other testicular neoplasms. Conclusion: Emerging field of UCNPs opens up new possibilities.
Methods: A 45-year-old male presented with palpable, painless Staining solutions and a novel device developed by us give hope for
mass in the right scrotum. There was no history of trauma or more accurate diagnosis by keeping the advantage of H&E staining
sudden enlargement of swelling. Plasma levels of β-hCG, AFP and combining it, in one image, with luminescent data, ideal for
and LDH were also within normal ranges. Testicular ultrasonog- generating ground truth for machine learning algorithms.
raphy demonstrated a heterogeneous, hipoechoic, well-
demarcated mass between the right medial testis and the head of
the epididymis. The tumour was hard in consistency with no ev- E-PS-CP-01-003
idence of invasion in the testis. Intraoperative frozen section was Nuclei segmentation of immunohistochemically stained slides using
done with neoplastic mass suspicion. transfer learning from classical histopathological domain
Results: Grossly the mass was 1.4 cm in diameter. Benign tumoral A. Ion Margineanu1, A. Serag1, H. Qureshi1, R. McMillan1, M. Saint
proliferation was considered in the frozen section. Testis reserved Martin1, A. Kennedy1, J. Diamond1, M. Salto-Tellez2, P. Maxwell2, P.
tumorectomy was preferred. Microscopically, the lesion was O'Reilly1, P. Hamilton1
unencapsulated. There was a proliferation of cells which form 1
Philips Digital & Computational Pathology, United Kingdom, 2 Queen's
cords and tubules with focal cytoplasmic vacuoles in the University Belfast, United Kingdom
fibrocollagenous stroma. Immunohistochemically, HBME-1,
Cytokeratin 7, D-2-40 and WT-1 showed positive reaction. Final Background & Objectives: The objective of this study was to create a
pathological diagnosis was made as AT. generic segmentation algorithm for immunohistochemically (IHC)
Conclusion: Normal levels of preoperative plasma tumour markers com- stained pathology slides, regardless of the IHC antibodies used for stain-
bined with intraoperative frozen section, when indicated, can avoid un- ing. Because of the large amount of annotations already available for
necessary orchiectomy, thereby preserving endogenous testicular func- classical histopathological slides stained with hematoxylin and eosin
tion and fertility potential. (HE), this study focused on transferring knowledge from one domain to
another.
Methods: A deep learning model was trained on 1000 HE images ac-
quired from different tissues, which were manually annotated for cell
E-Posters One-Day CPS nuclei by a senior pathologist. This model was tested on multiple cases:
4000 unseen HE images, 9000 counterstained IHC images, 1000 nuclei
stained IHC images, and 500 membrane/cytoplasm stained IHC images.
Sunday, 8 September 2019 – Wednesday, 11 September 2019 DICE scores for the segmented nuclei were computed as a performance
measure.
E-PS-CP-01 | 1-Day Computational Pathology Symposium
Results: The average DICE score for the test HE images was 72%,
while for the rest of the IHC images the average DICE scores were
E-PS-CP-01-001 around 50%.
Up-converting nanoparticles as a tool for histopathological tissue Conclusion: A deep learning model for nuclei segmentation trained only
evaluation with multiplexing and machine learning potential on images from the HE domain constitutes a good starting point for
K. Krawczyk1, S. Andersson-Engels2, A. Sjögren1 transfer learning towards the IHC domain.
1
Lumito AB, Sweden, 2 Biophotonics@Tyndall, Tyndall National
Institute, Cork, Ireland