Journal of Clinical and Translational Pathology 2024 vol.

4(1) | 36–43
DOI: 10.14218/JCTP.2023.00044

Mini Review

Introduction of the WHO Reporting System for Lymph Node

Cytopathology
Yan Gao1, Sara E. Monaco2, Ruth L. Katz3 and Y. Helen Zhang1*
1Department of Pathology and Laboratory Medicine, McGovern Medical School, The University of Texas Health Science
Center at Houston, Houston, TX, United States; 2Geisinger Medical Laboratories, Danville, PA, United States; 3Department
of Pathology, Chaim Sheba Hospital, University of Tel Aviv, Tel Aviv, Israel

Received: October 4, 2023 | Revised: November 27, 2023 | Accepted: December 7, 2023 | Published online: December 23, 2023

Abstract providing cells for immunophenotyping and molecular tests

with less morbidity. Cytology specimens are known to be
Lymph node fine needle aspiration biopsy (FNAB) is a useful particularly advantageous in providing intact well-preserved
diagnostic tool in the initial evaluation of lymphadenopathy
cells for FISH, flow cytometry, and other biomarker studies.1
of unknown etiology. The World Health Organization (WHO)
The quality of DNA and RNA may even surpass that derived
Reporting System for lymph node cytopathology comprises
from cells obtained by extraction from formalin-fixed, paraf-
five categories: Insufficient/Inadequate/Nondiagnostic, Be-
fin-embedded tissue biopsies.
nign, Atypical, Suspicious for Malignancy, and Malignant. This
review focuses on the diagnostic criteria for each category, Despite the advantages of FNAB in lymphoproliferative le-
including cytomorphology, ancillary studies, differential diag- sions, there was historically no formal classification system
nosis, and associated risk of malignancy. Its primary goal dedicated to lymph node cytopathology to improve stand-
is to standardize the reporting and interpretation of lymph ardization until a categorical system for performance, clas-
node samples, minimizing interobserver variability among sification, and reporting of lymph node cytopathology was
pathologists. By establishing clear guidelines and standard- proposed at the 20th International Congress of Cytology held
ized terminology, this system improves communication be- in Sydney in 2019.2 Recently, the WHO, the International
tween pathologists and clinicians, leading to enhanced con- Agency for Research on Cancer, and the International Acad-
sistency, accuracy, and patient care in lymph node specimen emy of Cytology have joined forces to create a series of In-
evaluation. The WHO Reporting System serves as a unified ternational Reporting Systems for Cytology, including lymph
and reproducible framework for the precise categorization of node cytology by an expert editorial board of cytopatholo-
lymph node aspirates, enabling better communication be- gists. The WHO Reporting System for lymph node cytology
tween cytopathologists and clinicians and ultimately facilitat- has established five categories based on clinical, radiologi-
ing more effective patient management. cal, and key cytopathological features with ancillary studies
for optimal diagnosis. This reporting system may lead to a
Citation of this article: Gao Y, Monaco SE, Katz RL, Zhang greater acceptance and utilization of FNAB, a better interdis-
YH. Introduction of the WHO Reporting System for Lymph ciplinary understanding of the results, and eventually benefit
Node Cytopathology. J Clin Transl Pathol 2024;4(1):36–43. patients.
doi: 10.14218/JCTP.2023.00044.

The WHO reporting system

Introduction Insufficient/Inadequate/Nondiagnostic

Lymph node fine needle aspiration biopsy (FNAB) is wide- Diagnostic criteria
ly used in current daily practice in the initial evaluation of
• No material for assessment (Fig. 1);
lymphadenopathy, particularly in lymph nodes that are dif-
• Technical problems, which prevent assessment and diag-
ficult to access with larger biopsy needles. The advantages
nosis of the material on the slides.
of FNAB are rapid turnaround time, low cost, ability to easily
perform morphological assessment and triage, and ease of Differential diagnosis and potential pitfalls
• Currently, there are limited publications defining the
Keywords: Lymph node; Cytology; Fine needle aspiration; Reporting system. criteria for adequacy on lymph nodes. This category in-
Abbreviations: CNB, core needle biopsy; FC, flow cytometry; FNAB, fine nee- cludes cases that cannot permit a reliable interpretation
dle aspiration biopsy; IHC, Immunohistochemical stains; NHL, non-Hodgkin due to qualitative and/or quantitative reasons, such as
lymphoma.; ROM, risk of malignancy; ROSE, rapid on-site evaluation; WHO,
the world health organization. scant cellularity, extensive necrosis, or technical limita-
*Correspondence to: Y. Helen Zhang, Department of Pathology and Labora- tions that cannot be overcome such as air-drying arte-
tory Medicine, McGovern Medical School, The University of Texas Health Science facts related to fixation and/or obscuring material and
Center at Houston, 6431 Fannin St, Houston, TX 77030, United States. ORCID:
https://orcid.org/0009-0008-6963-5115. Tel: +1-713-566-5918, Fax: +1-713- poor-quality smearing. Repeat FNAB or core needle bi-
566-5285, E-mail: [email protected] opsy (CNB) or excision biopsy should be requested based

Copyright: © 2023 The Author(s). This article has been published under the terms of Creative Commons Attribution-Noncommercial 4.0 International License
(CC BY-NC 4.0), which permits noncommercial unrestricted use, distribution, and reproduction in any medium, provided that the following statement is provided.
“This article has been published in Journal of Clinical and Translational Pathology at https://doi.org/10.14218/JCTP.2023.00044 and can also be viewed
on the Journal’s website at https://www.xiahepublishing.com/journal/jctp”.
Gao Y. et al: The WHO reporting system for lymph node cytopathology

Fig. 1. Non-diagnostic (a). The fine-needle aspiration of the subcarinal lymph node shows abundant bronchial epithelial cells only (DQ, 100×). Be-
nign (b–d). b. Polymorphous lymphocytes and tingible body macrophages of a reactive axillary lymph node (DQ, 100×). c–d. Foamy histiocytes with
abundant intra-/extracellular acid-fast bacilli and lymphocytes of a cervical lymph node with Mycobacterium avium complex infection (c. DQ, 400×;
d. Needle core biopsy: H&E, 200×; insert, acid-fast stain, 500×).

on the specific clinical context, particularly with rapid on- some of the literature to be adequate. A rare study con-
site evaluation (ROSE) (Fig. 2). Some studies defined an sidered the presence of clusters of anthracotic pigment-
adequate specimen to have lymphocytes beyond what laden macrophages on EBUS-FNA of mediastinal lymph
would be expected in normal blood.3 The amount of at nodes as indicators of adequacy.4 However, most studies
least 40 lymphocytes per high-power field in the most focused on EBUS-FNA of mediastinal lymph nodes sug-
cellular areas of air-dried DQ smear was recommended in gested that the presence of histocytes alone does not

Fig. 2. Rapid on-site evaluation (ROSE). RPMI: Roswell Park Memorial Institute (RPMI) medium or RPMI 1640; IHC: immunohistochemistry.

Journal of Clinical and Translational Pathology 2024 vol. 4(1) | 36–43 37

 Gao Y. et al: The WHO reporting system for lymph node cytopathology

Table 1. Summary of Risk of Malignancy Studies

Inadequate Benign Atypical Suspicious Malignant

Total
Studies Case Num- Case Num- Case Num- Case Num- Case Num-
Cases
ber/ROM* ber/ROM ber/ROM ber/ROM ber/ROM
Caputo et al.,6 2021 1,458 8/66.7% 716/9.38% 23/28.6% 58/100% 653/99.8%
Gupta et al.,7 2021 6,983 289/27.5% 3,397/11.5% 33/66.7% 96/88% 3,168/99.6%
Vigliar et al.,8 2021 300 20/50% 104/1.92% 25/58.3% 13/100% 138/100%
Torres Rivas et al.,9 2021 363 13/27% 208/3% 7/50% 21/100% 114/100%
Makarenko et al.,10 2022 349 24/58.3% 109/6.4% 52/69.2% 30/96.7% 134/99.3%
Uzun et al.,11 2022 504 24/16.6% 283/0.7% 36/88.8% 48/100% 113/100%
Ahuja et al.,12 2022 1,205 53/9.1% 488/1.5% 10/37.5% 275/96.9% 379/98.2%

*Abbreviation: ROM: risk of malignancy, based on histopathologic correlation and malignant outcomes.

necessarily determine the adequacy of the sample, but Differential diagnosis and potential pitfalls
they can be contributory when found in conjunction with
• A wide range of lymphoid patterns can be seen in viral
other cell types.5
infections, autoimmune processes, and other lesions.
• In some cases, with insufficient cytopathological lym-
These patterns include predominantly follicular hyper-
phoid material, needle rinsing may subsequently provide
plasia, immunoblastic reactions, prominent histiocyto-
diagnostic information from flow cytometry (FC) or cell
sis, prominent plasmacytosis and necrosis, or mixed
blocks or other ancillary testing such as cytogenetics,
findings;
due to improved sensitivity in hypocellular samples or
• If the features are benign but a precise diagnosis cannot
due to sample heterogeneity with passes obtained for an-
be made, the features should be described, and a differ-
cillary studies containing more adequate lymphoid tissue
ential diagnosis should be provided;
than seen on the aspirate smears.
• Distinguishing between follicular hyperplasia and follicu-
• Correlation with imaging and clinical findings is always
lar lymphoma, or between a viral immunoblastic reac-
important. For example, in this category for cases where
tion and lymphoma can be difficult in cytology speci-
there is good lymphoid material, but it does not explain
mens;
the imaging/clinical findings, either “nondiagnostic” or
• If the features raise a differential diagnosis that includes
“benign” can be used with the caveat that “the material
lymphoma, then the case is placed in the ‘Atypical’ cat-
may not represent the targeted lesion” and emphasizing
egory;
the need for clinical and radiological correlation.
• As with all categories, correlation with clinical and imag-
• In practice, one term from insufficient/inadequate/nondi-
ing findings, in addition to any pertinent serological tests
agnostic needs to be chosen and used consistently.
that are available, is mandatory. The ability to confident-
Risk of malignancy (ROM) and clinical management ly provide a diagnosis based on the cytomorphology of
recommendation lymph nodes is variable and can be misleading without
the use of additional information and ancillary studies.
Based on limited published studies, the prevalence of this Distinguishing between benign and atypical inflammatory
category is 0.55–6.9%, and the ROM ranges from 9.1% to reactive patterns can also be challenging and is influ-
66.7% (Table 16–12). Thus, a repeat FNAB with ROSE for ad- enced by many factors such as local practices, expertise,
equacy assessment and triage is recommended. Additionally, as well as the expectations and support of clinical col-
if feasible, a CNB with touch preparation and ROSE may be leagues;
considered. • A relatively low to intermediate ROM will allow for a high
negative predictive value (NPV) for a ‘Benign’ diagnosis:
Benign
1. One example: a young patient with a clinical presenta-
Diagnostic criteria tion of infectious mononucleosis, who has FNAB show-
ing a prominent immunoblastic component, could be
• Unequivocal benign features that may or may not be spe- watched to see if the lymphadenopathy recedes and if
cific for a particular infection or non-infectious process; serology and clinical outcomes correlate:
• Normal or reactive lymphoid components and inflamma- 2. Another example: a polymorphous lymphoid popu-
tory processes. lation with tingible-body macrophages and dendritic
cells in recognizable germinal centers on smears sug-
Entities and cytomorphologic features gests follicular hyperplasia. A provisional or prelimi-
• Inflammatory/Infectious processes: nary diagnosis of follicular hyperplasia (Fig. 1) can
◦◦ Acute inflammation; be made, with a comment of “Correlation with FC
◦◦ Granulomatous inflammation; is recommended. Repeat FNAB if lymphadenopathy
• Benign reactive lymphadenopathy: persists”. FC is very helpful to exclude a monoclo-
◦◦ Follicular hyperplasia (Fig. 1); nal B-cell population, and CNB may be considered. If
◦◦ Immunoblastic reactions; ancillary tests are not available, the patient may be
◦◦ Prominent histiocytosis (Fig. 1); watched for a 2-to-4-week period. If lymphadenopa-
◦◦ Prominent plasmacytosis; thy persists, repeat FNAB or excision biopsy is recom-
◦◦ Prominent necrosis. mended.

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Gao Y. et al: The WHO reporting system for lymph node cytopathology

Fig. 3. Atypical (a–b). Rare clusters of atypical cells and lymphocytes on smear slide but absent on the cell block slide from a pre-carinal lymph node
(a. DQ, 200×; b. H&E 100×). Suspicious for malignancy (c–d). Monomorphic atypical lymphocytes on FNA smear and core biopsy of a para-aortic lymph node,
which proved to be a low-grade follicular lymphoma (c. DQ, 400×; d. H&E, 100×).

Ancillary testing the observed features and provide a differential diagnosis

in the report.
• Special Stains: FNAB may demonstrate or suggest the
presence of infectious organisms in routine stains, prompt-
Atypical
ing the need for additional special stains. For instance, the
Ziehl-Neelsen stain for acid-fast bacilli, consistent with tu- Diagnostic criteria
berculosis, may aid in making the diagnosis; Scant or poorly prepared cellular material demonstrates pre-
• Additionally, in plasma cell-rich lesions with an amor- dominantly benign cytological features, while a few cells may
phous background material, a Congo Red stain may be show minimal features of atypia, raising the possibility of a
helpful in detecting amyloid deposition; malignant lesion (Fig. 3). Insufficient features either in num-
• Immunohistochemical stains (IHC): In situations where ber or quality to diagnose a benign or malignant process or
clinical and radiological findings suggest reactive lymph lesion. The “atypical” category helps maintain a high NPV for
nodes, lymphoid proliferation may be diagnosed as reac- the benign category.
tive without FC or IHC, and patients may be referred for
clinical follow-up. However, when clinical and/or imaging Entities and cytomorphologic features
findings are discrepant or suspicious, FNAB with immu- Atypia of uncertain significance (AUS) includes possible epi-
nophenotyping, preferably by FC or alternatively by IHC, thelial inclusions and non-lymphoid lesions such as histio-
is recommended if material is available; cytic proliferations.
• Molecular and FC: Ancillary testing, such as PCR and mi- • Atypical lymphoid cells of uncertain significance (ALUS)
crobiological culture for organisms, or a cell block for or- include any case in which the lymphoid material suggests
ganisms, enhances the diagnosis of a reactive lymphoid a benign process but cannot entirely exclude lymphoma.
population. For example, a mixture of lymphoid cell types with a rela-
tive lack of tingible body macrophages and small lympho-
Risk of malignancy (ROM) and clinical management cytes raises the differential diagnosis of follicular hyper-
recommendation plasia and follicular lymphoma.
Based on limited published studies, the prevalence of this
category is 31.2–56.1%, and the ROM ranges from 0.7% Differential diagnosis and potential pitfalls
to 11.5% (see Table 1). In certain cases, additional ancil- This category includes cases demonstrating features pre-
lary studies, such as special stains for tuberculosis, PCR, dominantly seen in benign lesions and minimal features that
and microbial culture for organisms, or flow cytometry to may raise the possibility of a malignant lesion, but with in-
exclude lymphoma, might be required. When an exact di- sufficient features either in quantity or quality to diagnose a
agnosis cannot be established, it is essential to describe benign or malignant process or lesion.

Journal of Clinical and Translational Pathology 2024 vol. 4(1) | 36–43 39

 Gao Y. et al: The WHO reporting system for lymph node cytopathology

Ancillary testing be definitive and upgrade the category. Repeat FNAB, core
Cytopathological features that make the smear atypical needle biopsy, or excisional biopsy is typically recommended.
should always be stated in the report, and the possible di-
Malignant
agnosis or differential diagnosis should be stated whenever
possible. Repeat FNAB, preferably with FC and cytogenet- Diagnostic criteria
ics, or CNB is required regardless of clinical and US findings.
ROSE should be considered, if available, to ensure adequate • Unequivocal cytopathological features of malignancy.
material and to triage appropriately.
Entities and cytomorphologic features
Risk of malignancy (ROM) and clinical management • Mixed lymphoid cell pattern:
recommendation ◦◦ Follicular lymphoma;
Based on limited published studies, the prevalence of this ◦◦ Marginal zone lymphoma;
category is 0.5–14.9%, and the ROM ranges from 28.6% to ◦◦ Angioimmunoblastic T-cell lymphoma;
88.8% (Table 1). Samples falling into this category require • Predominantly small/intermediate cell pattern:
repeat sampling for more material and ancillary studies, such ◦◦ Chronic lymphocytic leukemia;
as flow cytometry and cell block, CNB, or excisional biopsy. ◦◦ Mantle cell lymphoma;
Sometimes, a “wait and watch” approach may be applicable. ◦◦ Lymphoplasmacytic lymphoma;
◦◦ Plasma cell neoplasms;
Suspicious for malignancy ◦◦ Mastocytosis;
• Predominantly intermediate/pleomorphic/blastic cell pat-
Diagnostic criteria tern:
◦◦ Lymphoblastic lymphomas;
• Some cytopathological features suggestive of malignancy
◦◦ Large/Aggressive B cell lymphomas (Fig. 4);
but with insufficient features either in quantity or quality
◦◦ Burkitt lymphoma;
to make an unequivocal diagnosis of malignancy;
◦◦ Blastoid mantle cell lymphoma;
• This category supports a high positive predictive value
◦◦ Anaplastic large cell lymphoma;
(PPV) for the “malignant” category.
◦◦ Breast implant-associated anaplastic large cell lym-
Entities and cytomorphologic features phoma;
◦◦ Primary effusion lymphoma;
• Suspicious for lymphoma: Small and/or medium-sized, ◦◦ Peripheral T-cell lymphoma, NOS;
monomorphic atypical lymphoid cells (Fig. 3); polymor- ◦◦ Myeloid sarcoma;
phous lymphoid smears with rare Hodgkin or Reed-Stern- • Single very large, atypical cell pattern:
berg-like cells; large cell or Burkitt lymphomas with scant ◦◦ Classic Hodgkin lymphoma;
cellularity; ◦◦ Nodular lymphocyte predominant Hodgkin lymphoma;
• Suspicious for metastatic carcinoma: atypical epithelioid ◦◦ T-cell/histiocyte rich large B-cell lymphoma;
cells suspicious for metastasis. • Histiocytic and dendritic cell neoplasms:
◦◦ Langerhans cell histiocytosis;
Differential diagnosis and potential pitfalls
◦◦ Histiocytic sarcoma;
• Small and/or medium-sized, monomorphic atypical lym- ◦◦ Interdigitating dendritic cell sarcoma;
phoid cells suspicious for lymphoma, but the cytomor- ◦◦ Follicular dendritic cell sarcoma;
phology alone is not sufficient for diagnosis and FC or • Metastases:
IHC results are not available or do not demonstrate B-cell ◦◦ Metastases (Fig. 5).
monoclonality;
• Polymorphous lymphoid smears in which few Hodgkin or Differential diagnosis and potential pitfalls
Reed-Sternberg-like cells are detected, and IHC is not • Due to similarity in morphology on FNAB smears, it is dif-
performable or has not been diagnostic; ficult to make a precise diagnosis of a specific carcinoma,
• Large cells or Burkitt lymphomas with scant cellularity, lymphoma, or other malignancy. The precise diagnosis
and ancillary studies are not available; of carcinoma and lymphoma subtypes usually requires
• Smears in which atypical cells suspicious for metastasis ancillary testing;
are detected but are too scant to be diagnostic and there • The presentation of tumors in this WHO Reporting Sys-
is no CNB material available to perform IHC. tem follows the order found in the 5th edition WHO Clas-
sification of Hematopoietic and Lymphoid Tissues, but
Ancillary testing
not all tumors are included because they have not been
• Ancillary testing, including FC for non-Hodgkin lympho- described in the cytopathology literature.
ma (NHL) or cell block with IHC for Hodgkin lymphoma
or carcinoma, may be definitive and can “upgrade” the Ancillary testing
category. • This category includes small to medium-sized cells of
NHL supported by evidence of clonality shown by FC or
Risk of malignancy (ROM) and clinical management
molecular studies showing clonal immunoglobulin or T-
recommendation
cell receptor gene rearrangements, and all the entities
Based on limited published studies, the prevalence of this in which cytopathological features alone are sufficient to
category is 1.4–22.8%, and the ROM ranges from 88% to identify malignancy as large cell NHL. Most B-cell lym-
100% (Table 1). This category supports a high PPV for the phomas have characteristic immunophenotypic profiles
“malignant” category. Whenever possible, provide differen- (Table 2). However, no single marker is specific, thus a
tial diagnoses. Ancillary studies, including flow cytometry, panel of immunophenotypic markers is necessary;
cell block with IHC, or IHC performed on FNAB smears, may • This category also includes Hodgkin lymphoma (HL) in

40 Journal of Clinical and Translational Pathology 2024 vol. 4(1) | 36–43

Gao Y. et al: The WHO reporting system for lymph node cytopathology

Fig. 4. Malignant. Diffuse large B cell lymphoma, high grade, in a cervical lymph node: Isolated and loosely clustered large lymphoma cells on smears. The tumor
cells are positive for CD20 with a high Ki-67 proliferative index of >90% (a. DQ, 400×; b. H&E, 200×; c. CD20, 200×; d. Ki-67, 200×).

Fig. 5. Malignant Metastatic melanoma of right inguinal lymph node: atypical epithelioid cells with enlarged nuclei and prominent nucleoli and scattered dark granular pig-
ment consistent with melanin. The tumor cells are positive for Mart-1 and SOX10 (a. DQ, 400×; b–d. Needle core biopsy: b. H&E, 200×; c. Mart-1, 200×; d. SOX10, 200×).

Journal of Clinical and Translational Pathology 2024 vol. 4(1) | 36–43 41

 Gao Y. et al: The WHO reporting system for lymph node cytopathology

Table 2. Immunophenotypic and Genetic/Molecular Characteristics of Common Small B Cell Lymphomas

CD10/ Cyclin D1/

CD19 CD20 CD5 LEF1 CD23 CD200 Molecular Genetics
BCL6 SOX11
CLL + + dim + − + + + − del (13q); del (11q); del (17p); trisomy 12
MCL + + + − − − − + IGH::CCND1
FL + + − + − − − − IGH::BCL2
HCL + + − − − − + +weak BRAF p.V600E mutation
LPL + + −/+ −/+ − −/+ − − MYD88 p.L265P mutation
MZL + + −/+ − − −/+ − − BIRC3::MALT1; IGH::BCL10;
IGH::MALT1; IGH::FOXP1

Abbreviations: CLL, chronic lymphocytic leukemia; FL, follicular lymphoma; HCL, hairy cell leukemia; LPL, lymphoplasmacytic lymphoma; MCL, mantle cell lymphoma;
MZL, marginal zone lymphoma.

which there is an appropriate cellular background and both developed and low-middle-income countries, ultimately
diagnostic Hodgkin and Reed-Stern-berg cells as well as enhancing patient care and outcomes.
metastatic neoplasms. The second diagnostic level of the Overall, FNAB demonstrates high diagnostic accuracy in
WHO System provides additional information and identi- various lymph node disorders. It has many benefits such as
fication of specific entities by utilizing ancillary testing; minimal invasiveness, rapid turnaround time, cost-effective-
• Ancillary testing makes the diagnosis more specific and ness, and easy provision of cells for a variety of studies either
may change the category, as with all FNAB cytopathology for diagnostic or therapeutic purposes. Implementing the
(e.g., “suspicious for malignancy” to “malignancy”): proposed WHO system contributes to achieving uniformity
◦◦ For example, large cell lymphoma can be diagnosed and reproducibility in cytologic diagnoses and facilitates risk
on direct smears, confirmed on FC as a B-cell lym- stratification based on cytopathology. Optimal patient man-
phoma, and FISH for c-Myc and IGH-Bcl2 on the cell agement can be guided by understanding the risks of malig-
block material, can confirm a “double-hit” high-grade nancy associated with FNAB diagnostic categories. However,
lymphoma; the interpretation of FNAB requires awareness of certain in-
◦◦ Metastatic carcinoma in a mediastinal hilar lymph node herent pitfalls, such as sampling error or misinterpretation,
at Endobronchial Ultrasound Bronchoscopy (EBUS) can especially in lymphoma diagnosis. A critical element that
be diagnosed by cytopathology, and in many cases the might significantly improve the adoption and refinement of
diagnosis can be made, followed by limited IHC on the WHO system is to promote the involvement of hemato-
the cell block for definitive characterization in order pathologists, hematologists, and oncologists. Further stud-
to save material for potential molecular testing on the ies from multiple different centers with various epidemiologic
cell block or slide scraping to diagnose EGFR1, KRAS, settings and larger sample sizes are necessary to assess the
ROS1 and other biomarkers that correlate with therag- reliability and validity of this system.
nostic information.

Risk of malignancy (ROM) and clinical management Acknowledgments

recommendation None.
Based on limited published studies, the prevalence of this
category is 22.5–46%, and the ROM ranges from 98.2% to
Funding
100% (Table 1). This category demonstrates unequivocal cy-
tological evidence of malignancy. Ancillary studies such as None.
IHC, FC, and molecular tests are often required for a specific
diagnosis.
Conflict of interest
The manuscript was submitted during Dr. Y. Helen Zhang’s
Conclusions term as an editorial board member of Journal of Clinical and
The WHO Reporting System for Lymph Node Cytopathol- Translational Pathology. The authors have no other conflict
ogy plays a crucial role in standardizing nomenclature and of interests to declare.
reporting systems in cytopathology.13 It facilitates the inte-
gration of diagnostic and management algorithms, assisting
Author contributions
clinicians in effectively managing patients. Through inter-
national consensus, it establishes key diagnostic criteria in Study concept and design, data collection, analysis and in-
cytopathology, improving the quality of diagnostic assess- terpretation of data, literature review, and drafting of the
ment and reporting in lymph node cases. The system also manuscript (YHZ, YG, MS, KR). All authors have made a sig-
establishes a dynamic practical link between cytopathology nificant contribution to this study and have approved the final
and surgical pathology through its direct connection to the manuscript.
5th Edition of the World Health Organization Classification
of Hematolymphoid Tumors “blue book” on the website. By
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