Received: 22 June 2020 | Revised: 21 September 2020 | Accepted: 24 September 2020

DOI: 10.1111/jop.13127

ORIGINAL ARTICLE

Intravascular papillary endothelial hyperplasia in the oral

mucosa and jawbones: A collaborative study of 20 cases and a
systematic review

Carolina Clasen Vieira1 | Ana Paula Neutzling Gomes1 | Laylla Galdino dos Santos1 |
Douglas Silva de Almeida1 | Laura Campos Hildebrand2 | Isadora Luana Flores2 |
3 4
Jean Nunes dos Santos | Lauren Frenzel Schuch |
1
Ana Carolina Uchoa Vasconcelos

1
Diagnostic Center for Oral Diseases, School
of Dentistry, Universidade Federal de Abstract
Pelotas, Pelotas, Brazil Background: Intravascular papillary endothelial hyperplasia is an unusual vascular le-
2
Department of Conservative Dentistry,
sion characterized by the proliferation of endothelial cells. The aim of this study was
Oral Pathology area, School of Dentistry,
Universidade Federal do Rio Grande do Sul, to determine the frequency and general features of this lesion.
Porto Alegre, Brazil
Methods: Biopsy records of three oral pathology services were reviewed for intra-
3
Department of Pathology, Postgraduate
Program in Dentistry and Health, School of
vascular papillary endothelial hyperplasia cases from 1959 to 2020. In addition, a
Dentistry, Universidade Federal da Bahia, systematic review of case reports and case series was carried out in eight electronic
Salvador, Brazil
4
databases.
Department of Oral Diagnosis, Piracicaba
Dental School, Universidade de Campinas, Results: Of the 65 205 retrieved cases, 20 (0.03%) were diagnosed as intravas-
Piracicaba, Brazil cular papillary endothelial hyperplasia. Mean patient age was 46.55 years, and
Correspondence females (12 cases/60%) were more affected. The lower lip (9 cases/47.36%) was
Ana Carolina Uchoa Vasconcelos. Centro de the most commonly affected site, and the lesions were generally asymptomatic
Diagnóstico das Doenças da Boca – CDDB
– Faculdade de Odontologia, Universidade (7 cases/63.63%). Clinically, 90% of the lesions presented (18 cases) as a nodule,
Federal de Pelotas. Rua Gonçalves Chaves, with a mean size of 1.13 cm. The clinical diagnostic hypotheses most frequently
457, sala 607, Pelotas, RS, Brazil. CEP:
96015-560. raised were mucocele (6 cases/37.50%) and hemangioma (5 cases/31.25%). An
Email: [email protected] excisional biopsy was chosen in all cases for treatment. Forty-nine studies of the
Funding information systematic review were included, yielding 105 cases. The literature showed simi-
The authors thank the Coordination of
Improvement of Higher Education Personnel larity in all variables.
(Finance Code 001), Brazil. LFS is the Conclusion: Despite the uncommon frequency, clinicians and oral pathologists
recipient of fellowships. We would like to
thank the Brazilian National Council for should familiarize themselves with the similarities between intravascular papillary
Scientific and Technological Development endothelial hyperplasia and some other lesions in terms of clinical and histological
for financial support—JN dos Santos is a
research fellow of the Brazilian National features.
Council for Scientific and Technological
Development. KEYWORDS

differential diagnosis, hemangioma, Masson's tumor, mucocele, oral lesion

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

J Oral Pathol Med. 2021;50:103–113.  wileyonlinelibrary.com/journal/jop | 103

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104 VIEIRA et al.

1 | I NTRO D U C TI O N in the oral mucosa and jawbones was performed at three oral pa-
thology centers in Brazil. Part 2 consisted of a systematic review
Intravascular papillary endothelial hyperplasia (IPEH) is a benign, of case reports and case series of patients diagnosed with IPEH.
non-neoplastic, and uncommon vascular lesion characterized by ex-
cessive endothelial proliferation.1-3 IPEH is a benign non-neoplastic
lesion that was first described in 1923 by Dr Pierre Masson, who 2.1 | Part 1: Retrospective analysis of oral
named this rare finding as “vegetant intravascular hemangioendo- pathology services
thelioma.”4 Later, other authors referred to the same entity using
different term such as “intravascular angiomatosis”,5 “Masson's 2.1.1 | Ethical approval and study design
6 7
tumor”, “Masson's hemangioma”, “Masson's pseudoangiosar-
coma”,8 and “Masson's lesions”.9 The term IPEH was first used by The study was approved by the Ethics and Research Committee of
Clearkin in 1976, based on the understanding that the entity is a the Federal University of Pelotas and patients' confidentiality and
reactive phenomenon rather than a true neoplasm.10 anonymity were guaranteed according to the Helsinki Declaration.
This lesion comprises approximately 2% of all vascular tumors of Biopsy records were obtained from three oral and maxillofacial
the skin and subcutaneous tissue and predominantly occurs in the pathology services, that is, Department of Oral Pathology of the
trunk, fingers, and head and neck regions.11,12 The literature points Federal University of Bahia, Diagnostic Center for Oral Diseases of
out that some factors may be associated with the triggering of the the Federal University of Pelotas, and Department of Oral Pathology
proliferation, such as local minor trauma, hormonal influence, and of the Federal University of Rio Grande do Sul. A retrospective eval-
changes in some growth factor stimulations.13,14 IPEH is classified uation of case records was performed.
into three types: The primary type arises within the lumen of a di-
lated vessel; the second develops in a preexisting vascular lesion,
such as a hemangioma, pyogenic granuloma, or arteriovenous mal- 2.1.2 | Sample and data collection
formation, and the third and most rare variant of IPEH is a papillary
hyperplasia of extravascular origin.3,15 Biopsy request records of specimens submitted to histopatho-
The frequency of IPEH is not common in the oral cavity, and logic examination with a diagnosis of IPEH were recorded. Two
only a few cases have been published in the English literature thus independent researchers performed data collection. Data regard-
far.16 Oral IPEH seems to have a preference for females and pres- ing patient age and sex, anatomical location, symptoms, clinical
ents the lower lip is the most commonly affected site, followed by aspects, radiographic features, size of lesion, clinical diagnosis,
buccal mucosa, upper lip, and tongue. Clinically, the lesions are de- type of the lesion, immunohistochemistry analysis, and treatment
scribed as asymptomatic, firm, and sometimes as nodules or masses were recorded. The anatomical location of the lesion was consid-
of reddish-blue coloration with slow growth and slight elevation.16 ered as follows: lip (upper/lower), buccal mucosa, tongue lower
Intraosseous IPEH lesions in the jaws are extremely rare, and only alveolar bridge, and floor of the mouth. If intraosseous, the jaws
four cases have been reported in the literature.12 Histopathologically, were classified as: 1) anterior: lesions in the incisor/canine region
endothelial cells proliferate in a papillary pattern toward the lumen and 2) posterior: lesions in premolar/molar and retromolar/ramus
of the enlarged blood vessel from the area of the organizing throm- region.
bus. 2,16,17 Treatment consists of total excision into healthy margins, All histopathological slides were reviewed by an experienced oral
the prognosis is excellent and recurrence rates are low.16,18 and maxillofacial pathologist at each center. IPEH mainly demon-
No surveys studies with a larger number of oral IPEH have been strated in HE staining numerous papillary processes located in the
published in the English literature thus far. Considering the impor- direction of the vascular lumen; the cells were covered by a single
tance of knowing and determining the clinical, radiological, and layer of endothelium.19,20
histopathological profile of the population affected by IPEH, the
objective of the present study was to analyze the clinical features
of IPEH cases diagnosed at three Brazilian oral pathology services 2.2 | Part 2: Systematic literature review of case
and to compare them to the data reported in a systematic literature reports or case series of patients with a histological
review. The present article provides information that can improve diagnosis of IPEH in the oral mucosa and jawbones
diagnostic accuracy, allowing surgeons and pathologists to make in-
formed decisions. 2.2.1 | Protocol and registration

This systematic review was conducted according to the Preferred

2 | M ATE R I A L S A N D M E TH O DS Reporting Items for Systematic Reviews and Meta-analyses
(PRISMA) Statement. 21 A protocol was drafted and registered
The study consisted of two parts. In Part 1, a retrospective analy- with the International Prospective Register of Systematic Review
sis of the cases with a histopathological diagnosis of IPEH located (PROSPERO) (CRD42018100093).
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VIEIRA et al. 105

2.2.2 | Search strategy 2.2.5 | Data extraction and data items

The search was carried out in August 2020 using the following da- The same two authors independently performed data extraction
tabases: PubMed (National Library of Medicine), Web of Science from the included articles. The data collected from the studies in-
(Thomson Reuters), Scopus (Elsevier), Ovid MEDLINE (Wolters cluded were as follows: author's name, year of publication, country
Kluwer), ScienceDirect (Elsevier), BVS (BIREME), LIVIVO (ZD MED), where the case(s) was (were) reported, number of case(s) reported,
Embase (Elsevier). The following search strategy and keywords age and sex of the patient, anatomical location (soft and osseous tis-
were used for PubMed, Web of Science and Scopus: (masson's sue), symptoms, clinical aspects, radiographic features (internal ap-
hemangioma) OR (intravascular papillary endothelial) OR (mas- pearance/radiological locularity/image definition), size of the lesion,
son's tumor) OR (papillary proliferation of the endothelium) OR clinical diagnosis, type of the lesion, immunohistochemistry analysis,
(papillary fibroendothelioma) OR (intravascular endothelioma) OR and treatment.
(papillary endothelioma) OR (intravascular angiomatosis) OR (mas-
son's vegetant intravascular hemangioendothelioma) OR (masson's
pseudoangiosarcoma) OR (intravascular endothelial hyperplasia) OR 2.2.6 | Quality assessment of the studies
(masson's lesion) OR (papillary endothelial hyperplasia) OR (intra-
venous atypical vascular proliferation) OR (vegetant intravascular The included articles were critically appraised using the Joanna
hemangioendothelioma). Briggs Institute (University of Adelaide) tool for case reports or
Moreover, manual searches were conducted by cross-checking case series. 22 The references included were evaluated according
the reference lists of the included articles to identify publications to the following parameters: a clear description of patient's demo-
that might have been missing during the searches in the electronic graphic characteristics, medical history, and current clinical condi-
databases. The identified studies were inserted into a database tion, as well as a clear description of the propaedeutic approach,
using the EndNote software (Thompson Reuters). Duplicates were treatment, post-intervention clinical condition, adverse events,
removed upon identification. and lessons provided by the case report (ie, histopathological anal-
ysis with representative images). For each parameter, the included
article could be awarded a “yes,” “no,” “unclear” or “not applicable”
2.2.3 | Eligibility criteria comment.

Eligibility criteria included publications reporting cases of IPEH in

oral mucosa and jawbones. The studies needed to have histological 2.3 | Data analysis
information for confirmation of the diagnosis. The literature review
was carried out without restriction of language and year of publica- A descriptive analysis of the data was performed using the Statistical
tion. Studies that did not provide data about sex, age, or anatomical Package for the Social Sciences (SPSS) software, version 22.0 (SPSS
location or that were not available for full-text reading were ex- Inc) to characterize the following variables: patient's age and sex,
cluded. In addition, review papers, letters to the editor, and editorials anatomical location, symptomatology, clinical aspects, radiographic
commenting about other published articles were excluded. features, size, clinical diagnosis, and treatment. The mean and per-
centages are reported as descriptive statistics.

2.2.4 | Study selection

3 | R E S U LT S
The identified articles were exported to the EndNote software
(Thompson Reuters). After removing duplicates, articles were eval- 3.1 | Part 1
uated in two phases. In the first phase, only titles/abstracts were
analyzed according to the inclusion criteria by two authors (LGS and 3.1.1 | Sample and data collection
DGS). The calibration of the reviewers was obtained by using the
assessment of titles/abstracts of the first 50 references retrieved A total of 65,205 oral biopsies were performed at the three Brazilian
during the searches. The agreement between reviewers had a kappa centers studied, and 20 (0.03%) received a histopathological diagnosis
value of 0.96. If the title/abstract did not provide enough informa- of IPEH (Figure 1). The mean age at diagnosis was 46.55 (SD ± 20.46)
tion for the inclusion or exclusion decision, the next phase was con- years (range: 9-76 years). A total of 12 (60%) cases occurred in females
ducted. In phase 2, the full text of the articles was read, and the same and eight (40%) in males (female-to-male ratio: 1.5:1). Of the cases
eligibility criteria as described above were applied. Disagreements whose anatomical location was reported, nine (47.36%) occurred on the
were solved by discussion between the authors. If necessary, a third lower lip, three (15.78%) on the buccal mucosa and tongue; one case
author decided whether or not to include the study. Articles that met (5.26%) each was detected on the lower alveolar bridge, on the lip, on
those criteria were included. the posterior mandible and on the floor of the mouth. Symptomatology
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106 VIEIRA et al.

F I G U R E 1 Clinical aspect of a purplish

(A) (B)
papule in the lower lip mucosa (A) and
(B). Hematoxylin and eosin (H&E) stained
sections show a well-circumscribed
lesion comprised of vascular spaces
admixed with cellular areas, 20× (C).
Papillary proliferation of endothelial cells
toward vessel lumen, 200× (D) papillary
projections of fibrin cores (A) covered by
endothelial cells (B) [Colour figure can be
viewed at wileyonlinelibrary.com]
(C) (D)

was reported for 11 cases. Of these, 7 (63.63%) were asymptomatic cases (25.72%) in Asia. Mean patient age was 45.96 (SD ± 20.42) years
and four (36.37%) symptomatic. Eighteen cases (90%) manifested as (range: 2-83 years). Sixty-one (58.10%) individuals were women and
nodules and one (5%) as a bubble. One case (5%) presented a radiolu- 44 (41.9%) were men (female-to-male ratio: 1.39:1). Regarding ana-
cent, unilocular, and well-defined image. The mean size of the lesion tomical location, 37 (35.92%) cases occurred in the lower lip, followed
was 1.13 cm (0.5-2.2 cm). The provisional clinical diagnoses included by buccal mucosa (24 cases/23.30%), tongue (17 cases/16.51%),
mucocele (6 cases/37.50%), hemangioma (5 cases/31.25%), fibroma upper lip (14 cases/13.59%), labial commissure (4 cases/3.89%),
(2 cases/12.50%), traumatic neuroma (1 case/6.25%), residual cyst (1 posterior mandible (3 cases/2.91%), palate (2 cases/1.94%), anterior
case/6.25%), and benign mesenchymal neoplasia (1 case/6.25%). All mandible (1 case/0.97%), and floor of mouth (1 case/0.97%). Thirty-
cases (100%) were pure type. Immunohistochemistry analysis was two patients (62.75%) reported no symptomatology. Regarding the
made in three cases (15%) using CD34, CD31, Smooth Muscle Actin clinical aspects, 58 cases (95.08%) presented as nodule lesions and
(SMA), and Vimentin, showing positive staining. All cases (100%) were 1 case (1.64%) manifested as a papule. The mean size of informed
treated by excisional biopsy. IPEH cases was 1.55 cm (range: 0.2 to 6.0 cm). All four intraosseous
The full characteristics of all 20 cases are described in Table 1. cases showed radiolucent multilocular images. Half of them were ill-
defined in appearance and the others were well-defined. The clini-
cal diagnoses included hemangioma (32 cases/32.66%), mucocele
3.2 | Part 2 (16 cases/26.33%), pyogenic granuloma (9 cases/9.19%), epulis/
fibroma/papilloma (6 cases/6.12%), IPEH (5 cases/5.10%), tumor
3.2.1 | Study selection (3 cases3.06%), vascular malformation (3 cases/3.06%), angiosar-
coma (2 case/2.04%), muco-retention cyst (2 case/2.04%), nevus (2
The search strategy yielded 5586 references. After removal of 2578 cases/2.04%), phlebectasia (2 cases/2.04%), pleomorphic adenoma
duplicates, inclusion and exclusion criteria were applied to 3008 ref- (2 cases/2.04%), thrombus (2 cases/2.04%), adenoid cystic carcinoma
erences. Eighty-four articles were selected for full-text assessment (1 case/1.02%), angioma (1 case/1.02%), being mesenchymal neo-
and 46 of them were included according to the inclusion criteria. plasm (1 case/1.02%), benign neural tumor (1 case/1.02%), giant cell
Also, three studies were added from the manual search. A total of 49 peripheral granuloma (1 case/1.02%), hematoma (1 case/1.02%), in-
articles reporting 105 cases were incorporated into this systematic flammation (1 case/1.02%), lymphadenitis (1 case/1.02%), melanoma
review. The flowchart of the study selection process is presented in (1 case/1.02%), phlebolith (1 case/1.02%), salivary gland tumors (1
Figure 2. case/1.02%), and varicose veins (1 case/1.02%). Regarding type of
the lesion, pure form was observed in thirty cases (51.72%), mixed
in twenty-seven cases (46.55%), and extravascular in 1 case (1.73%).
3.2.2 | Data extraction and data items Immunohistochemistry markers included: CD34 (28 cases/22.05%),
Vimentin (21 cases/16.44%), Ki-67 (17 cases/13.39%), Factor VIII (14
Articles from three continents were included. Forty-seven (44.76%) cases/11.02%), SMA (14 cases/11.02%), Laminin (11 cases/8.66%),
cases were reported in America, 31 cases (29.52%) in Europe, and 27 CD105 (4 cases/3.15%), CD31(4 cases/3.15%), Type IV collagen
 VIEIRA et al.

TA B L E 1 General features of intravascular papillary endothelial hyperplasia diagnosed at three Brazilian Oral and Maxillofacial Pathology Centers

Size of
Age Clinical lesion Type of Immunohistochemical
Institution (y) Sex Anatomical location Symptom aspects Radiographic features (cm) Clinical diagnosis the lesion analysis Treatment

UFPEL 55 F Lower lip No Nodule NA 1.0 Mucocele Pure Not realized Excisional biopsy
UFPEL 15 M Lower lip No Nodule NA 0.9 Mucocele Pure CD34 (+), SMA (+), Excisional biopsy
vimentin (+)
UFPEL 35 M Lower lip Yes Nodule NA 1.0 Traumatic neuroma Pure Not realized Excisional biopsy
UFPEL 30 M Lower lip No Nodule NA 0.6 Mucocele Pure Not realized Excisional biopsy
UFPEL 76 F Lower lip Yes Nodule NA 1.5 Mucocele Pure Not realized Excisional biopsy
UFPEL 60 F Posterior mandible No Intraosseous Radiolucent, unilocular, 0.7 Residual cyst Pure CD34 (+) Excisional biopsy
and well defined
UFPEL 60 M Buccal mucosa NI Nodule NA NI Fibroma Pure Not realized Excisional biopsy
UFPEL 9 F Buccal mucosa NI Nodule NA 2.0 NI Pure Not realized Excisional biopsy
UFPEL 14 F Tongue Yes Nodule NA 2.0 Fibroma Pure Not realized Excisional biopsy
UFPEL 54 F Lower alveolar Yes Nodule NA 2.0 Hemangioma Pure Not realized Excisional biopsy
bridge
UFRGS 64 F Floor of the mouth NI Nodule NA 1.0 Hemangioma Pure Not realized Excisional biopsy
UFRGS 56 M Tongue No Nodule NA 0.8 Benign Pure Not realized Excisional biopsy
mesenchymal
neoplasia
UFRGS 54 F Lower lip No Bubble NA 0.5 Hemangioma Pure Not realized Excisional biopsy
UFRGS 61 M Lower lip NI Nodule NA 0.5 Hemangioma Pure Not realized Excisional biopsy
UFRGS 33 M Lower lip NI Nodule NA 1.0 Mucocele Pure CD31 (+) Excisional biopsy
UFBA 76 F NI NI Nodule NA 2.2 NI Pure Not realized Excisional biopsy
UFBA 53 F Lip NI Nodule NA 0.6 NI Pure Not realized Excisional biopsy
UFBA 35 M Tongue NI Nodule NA 0.8 Hemangioma Pure Not realized Excisional biopsy
UFBA 25 F Lower lip NI Nodule NA 0.5 Mucocele Pure Not realized Excisional biopsy
UFBA 66 F Buccal mucosa No Nodule NA 2.0 NI Pure Not realized Excisional biopsy

Abbreviations: F, female; M, male; NA, not applicable; NI, not informed; SMA, smooth muscle actin.
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108 VIEIRA et al.

FIGURE 2 Flowchart of the literature

search

(4 cases/3.15%), Podoplanin (3 cases/2.36%), Type I collagen (3 The patient's history, post-intervention clinical condition, and
cases/2.36%), UEA-1 (2 cases/1.57%), GLUT-1 (1 case/0.79%), PCNA adverse or unanticipated events were not clearly described in
(1 case/0.79%). Treatment was reported for 92 cases and an exci- most of the articles (Figure 3). In addition, all articles provided takea-
sional biopsy was the choice for all of them. The full characteristics way lessons.
of all included articles are summarized in Table 2 and Table S1.

4 | D I S CU S S I O N
3.2.3 | Quality assessment
In the current collaborative study, 20 IPEH were identified at three
All included articles were case reports or case series studies. Most different reference centers of oral pathology. To the best of our
of them provided a clear description of the patient's demographic knowledge, this is the first and largest study reporting the frequency
characteristics, patient's medical history, current clinical condi- of IPEH in the English literature. In this Brazilian survey, IPEH rep-
tion as well as the diagnostic tests and treatment procedures. resented 0.03% of cases among the entire sample of diagnosed oral
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VIEIRA et al. 109

TA B L E 2 Demographic data and clinical features of the 105 TA B L E 2 (Continued)

cases of Intravascular Papillary Endothelial Hyperplasia
Variable N (%)
Variable N (%)
Pyogenic granuloma 9 (9.19)
Continent, n = 105 Epulis/fibroma/papilloma 6 (6.12)
America 47 (44.76) Intravascular papillary endothelial hyperplasia 5 (5.10)
Europe 31 (29.52) Tumor 3 (3.06)
Asia 27 (25.72) Vascular malformation 3 (3.06)
Age, mean (SD, min-max), n = 105 45.96 Angiosarcoma 2 (2.04)
(±20.42,
Muco-retention cyst 2 (2.04)
2-83)
Nevus 2 (2.04)
Sex, n = 105
Phlebectasia 2 (2.04)
Female 61 (58.10)
Pleomorphic adenoma 2 (2.04)
Male 44 (41.90)
Thrombus 2 (2.04)
Ratio 1.39:1
Adenoid cystic carcinoma 1 (1.02)
Anatomical location, n = 103
Angioma 1 (1.02)
Soft tissue
Benign mesenchymal neoplasm 1 (1.02)
Lower lip 37 (35.92)
Benign neural tumor 1 (1.02)
Buccal mucosa 24 (23.30)
Giant cell peripheral granuloma 1 (1.02)
Tongue 17 (16.51)
Hematoma 1 (1.02)
Upper lip 14 (13.59)
Inflammation 1 (1.02)
Labial commissure 4 (3.89)
Lymphadenitis 1 (1.02)
Palate 2 (1.94)
Melanoma 1 (1.02)
Floor of mouth 1 (0.97)
Phlebolith 1 (1.02)
Osseous tissue
Salivary gland tumor 1 (1.02)
Posterior mandible 3 (2.91)
Varicose veins 1 (1.02)
Anterior mandible 1 (0.97)
Type, n = 58
Symptoms, n = 51
Pure 30 (51.72)
No 32 (62.75)
Mixed 27 (46.55)
Yes 19 (37.25)
Extravascular 1 (1.73)
Clinical aspects, n = 61
Immunohistochemistry, n = 127b
Nodule 58 (95.08)
CD34 28 (22.05)
Intraosseous 2 (3.28)
Vimentin 21 (16.54)
Papule 1 (1.64)
Ki-67 17 (13.39)
Radiographic features
Factor VIII 14 (11.02)
Internal appearance, n = 7
SMA 14 (11.02)
Radiolucent 6 (85.71)
Laminin 11 (8.66)
Mixed 1 (14.29)
CD105 4 (3.15)
Radiological locularity, n = 7
CD31 4 (3.15)
Multilocular 6 (85.71)
Type IV collagen 4 (3.15)
Unilocular 1 (14.29)
Podoplanin 3 (2.36)
Image definition, n = 5
Type I collagen 3 (2.36)
Well defined 5 (100.00)
UEA-1 2 (1.57)
Size of the lesion(cm), mean (min-max), n = 65 1.55 (0.2-6.0)
a GLUT-1 1 (0.79)
Clinical diagnosis, n = 98
PCNA 1 (0.79)
Hemangioma 32 (32.66)
Treatment, n = 92
Mucocele 16 (16.33)
Excisional biopsy 92 (100.00)
a
In some cases, more than one clinical hypothesis was considered.
(Continues) b
In some cases, more than one marker was positive.
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VIEIRA et al.

F I G U R E 3 Quality assessment of the included studies. Green circle indicates the study reported the evaluated item; red circle indicates
the study did not report the evaluated item; and yellow circle indicates the study did not define the evaluated item [Colour figure can be
viewed at wileyonlinelibrary.com]
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VIEIRA et al. 111

and maxillofacial lesions. This rate was also low in other retrospec- Intravascular papillary endothelial hyperplasia represents a dif-
tive studies of oral diagnosis centers, such as a relative frequency of ficult diagnosis because of its rarity and confusing histopathological
0.008%23 and 0.01%. 24 appearance. Therefore, a correct diagnosis consists of careful histo-
Although the etiology of the condition is still uncertain, multi- morphological examination, sometimes, in conjunction with immuno-
factorial events appear to be associated. Secondary factors—for histochemistry staining.31 The most important finding is the formation
example, local trauma and previous vascular disorders—account for of endothelium-lined papillary structures confined within the vascu-
approximately 30% of the cases, but the triggering stimulus cannot lar lumen.20 The papillary structures are covered by a single layer of
25
be identified in 70% of them. Some theories suggest that the exces- swollen or plump endothelial cells around a core of fibrous connective
sive endothelial proliferation stimulated by the local production of tissue.11,19,31 The papillae might fuse, resulting in a network of vascular
20,26
growth factors could explain the causative factor of IPEH. In this channels and the presence of papillary fronds, interconnected vascu-
sense, several authors have suggested an estrogenic hormonal influ- lar channels, and plump hyperchromatic endothelial cells in IPEH can
ence on the development of IPEH.12,16,24 This fact could reflect the simulate angiosarcoma.32,33 However, the intravascular confinement,
predominance of the disease among women, observed in both parts lack of necrosis and mitosis, and the presence of organizing thrombi
of the current study. Regarding age, individuals were more affected favor IPEH. Moreover, it is necessary to pay special attention to the
in the 5th decade of life. The mean age was 46.55 and 45.93 years difference between IPEH and other confounding lesions: although
for the collaborative and systematic review, respectively. endothelial cells are also a prominent feature in pyogenic granuloma,
Clinically, IPEH has no specific or pathognomonic signs. 27 The no surrounding vascular cell is evident; Kaposi's sarcoma is a low-
present collaborative study shows that the lower lip, buccal mu- grade vascular tumor and has no papillary fronds; rather, it displays
cosa, and tongue were the most common locations for oral IPEH— anastomosing slit-like vessels associated with a fascicular pattern of
similar to was observed in the systematic review. These regions spindle-shaped cells, a plasma cell infiltrate, and hemosiderin pigment
are known to be sites where minor trauma is very likely to occur, deposition.26 Other histological differential diagnoses of IPEH include
supporting the possibility that this factor may contribute to the spindle cell hemangioma, mucocele, hemangioendothelioma, malig-
development of IPEH. The present collaborative study also shows nant endovascular papillary angioendothelioma or Dabska's tumor,
that IPEH manifests predominantly as a small asymptomatic nod- and intravascular endothelioma.
ule. Concerning differential diagnosis, IPEH was not considered as Three varieties of papillary endothelial hyperplasia are described
a hypothesis in most cases in either the collaborative or the sys- in the literature according to their relationship with a vessel.3,15 The
tematic review. For the 20 cases reported in the current study, the primary type arises within the lumen of a dilated vessel and corre-
main clinical hypothesis was mucocele, followed by hemangioma. sponds to the pure form. The mixed form develops in a preexisting
The systematic review showed similarity to Brazilian findings, ex- vascular neoplasm, such as a hemangioma, pyogenic granuloma, or
cept for the order of clinical hypothesis: hemangioma as the most arteriovenous malformation. The extravascular type is the most rare
frequent, followed by mucocele. The clinical aspects of these le- variant. In the present research, both in collaborative and systematic
sions shared similarities with IPEH, that is, they more frequently review, the pure form was the most frequent.
affected the lower lip and presented as a small nodule. 28,29 Other Immunohistochemical investigations could be useful when the
lesions need to be excluded such as lesions of minor salivary gland endothelial origin of the lesion is in question.19 In the present sys-
origin (benign vs. malignant salivary gland tumors), reactive and tematic review, fourteen different immunohistochemical markers
neoplastic neural lesions (traumatic neuroma, neurofibroma, neu- were observed in tirthy-eight cases. CD34, Vimentin, and Ki-67
rilemoma), benign neoplasms of smooth muscle (leiomyoma), and were the most frequent immunohistochemical markers that suggest
non-odontogenic soft-tissue infection. In summary, an accurate the benign behavioral vascular of IPEH, in some cases, must be accu-
diagnosis of IPEH can be challenging if only clinical features are rately evaluated by histomorphological examination in conjunction
considered. with immunohistochemical analysis. Immunohistochemical analysis
Intraosseous lesions could present just as a slight bone-hard was made in 15% of cases of collaborative study, using CD34, CD31,
16
swelling covered with normal mucosa. The radiographic features and SMA. All markers show a positive staining.
in the four cases found in the systematic review presented as radio- An excisional biopsy was the treatment in all 20 cases of our
lucent multilocular images similar to those observed in some odon- survey and all 84 reported cases of the systematic review. In this
togenic lesions such as ameloblastoma and odontogenic keratocyst. respect, the best treatment described is a total excision-biopsy
However, computed tomography (CT) of the cases of the present with healthy margins. 33 However, Fontes et al23 reported that in
study revealed a unilocular hypodense well-defined image resem- some cases excision can cause substantial bleeding, and sclero-
bling a residual cyst. CT with contrast media or magnetic resonance therapy with sodium tetradecyl sulfate before surgery might be
imaging can determine the extent of the lesion; pool scintigraphy, indicated in these cases. 23 In addition, preoperative embolization
ultrasound, and color doppler sonography can improve the assess- could greatly contribute to the control of bleeding during the op-
ment of vascularity and assist the surgeon regarding the risk of un- eration of osseous lesions. When completely resected, recurrence
controllable intraoperative bleeding. 23,30 is extremely rare. 3,20
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112 VIEIRA et al.

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