Epithelioid Hemangioendothelioma in the Tongue: A Rare Case Report
Deniz SURMELI CIRKIN1, Ilke Evrim SECINTI1, Esin DOGAN1, Gul SOYLU OZLER2
1Department of Pathology, Hatay Mustafa Kemal University, Faculty of Medicine, Hatay, Turkey
2Department of Otorhinolaryngology, Hatay Mustafa Kemal University, Faculty of Medicine, Hatay, Turkey
Keywords: Hemangioendothelioma, Tongue, Oral cavity
Epithelioid hemangioendothelioma is a rare malignant vascular neoplasm caused by the proliferation of neoplastic endothelial cells. Epithelioid
hemangioendothelioma may develop in any organ, but it is commonly observed in the extremities. The tongue is a very unusual location for
A 55-year-old male patient presented to the outpatient head and neck clinic with lumps in the tongue, pain, and limitation of motion. The
polypoid mass detected in the anterior midline of the tongue was excised. Microscopically, the tumor cells included slightly pleomorphic oval
or round vesicular nuclei with an eosinophilic cytoplasm that variably contained vacuoles. There were 4 mitoses per 10 high power fields and
there was no necrosis. In immunohistochemical study, the tumor cells were positively stained with CD31 and CD34 whereas they were negatively
stained with TFE3, SMA, S-100, HHV-8 and EMA. The patient was diagnosed with “epitheloid hemangioendothelioma”.
Only ten cases have been reported in the tongue in the literature. Our case was the eleventh case, and we aimed to report this case as a rare entity
with an unusual location.
Enzinger and Weiss have classified hemangioendothelioma
lesions as epithelioid, kaposiform, hobnail (dabskaretiform),
composite and epithelioid sarcoma-like hemangioendothelioma
. Epithelioid hemangioendothelioma
(EHE) is a rare malignant vascular neoplasm caused
by the proliferation of neoplastic endothelial cells 2
Epithelioid hemangioendothelioma commonly develops in
the extremities, but it may be also seen in any organ such
as the liver, breast, lungs, and long bones 3
. It is rarely
seen in the head and neck including the submandibular
region, parotid gland, and oral cavity 4,5
. Only 31 cases
have been reported in the oral cavity in the literature 6
The gingiva is the most common location in the oral cavity,
followed by the tongue, and the maxillary and buccal
mucosa, respectively 6,7
. Only ten cases of epithelioid
hemangioendothelioma of the tongue have been reported
in the literature 63
EHE is driven by WWTR1-CAMTA1 or YAP1-TFE3
fusion genes 8,9. EHEs that occur due to WWTR1-
CAMTA1 fusion gene express CAMTA1 while those
occurring due to YAP1-TFE3 fuse gene express TFE3
(less specifically). WWTR1-CAMTA1 fusion is positive in
90% of hemangioendothelioma cases 8. Microscopically; endothelial cell proliferation with round nuclei and
eosinophilic cytoplasm are observed. There is frequent
cytoplasmic vacuolization. These vacuoles vary in size, but
are occasionally large blister-like structures that disrupt the
shape of the cell 1. This is characterized by proliferating
layers, cords, and islands of eosinophilic round or ovalshaped
epithelioid cells intertwining with spindle cell
threads around proliferating small blood capillaries 10.
Tumor cells express positivity with endothelial markers
such as CD31, CD34, ERG, and von Willebrand factor
(VWF). VWF provides high specificity with cytoplasmic
labeling while CD31 and CD34 are more sensitive 11.
A 55-year-old male patient presented to the outpatient head
and neck clinic with lumps in the tongue, pain, and limitation
of motion. A polypoid lesion was detected in the anterior
midline of the tongue. There was no pathological finding
in the laboratory tests. The mass was completely excised
and the tissue was sent to the Department of Pathology for
histopathologic evaluation. Macroscopically, a 1.4x1x0.3
cm gray-white colored polypoid mass was observed. The
sectional surface was observed to have a brown-gray
colored hemorrhagic appearance. Microscopically, a tissue
sample with non-keratinized acanthotic epithelium was containing an ulcer. A tumor with an infiltrative border
was encountered under the ulcer. The tumor consisted
of cells with slightly pleomorphic oval or round vesicular
nuclei in the fibrous stroma and eosinophilic cytoplasm
that variably contained vacuoles (Figure 1A
erythrocytes were found both in the vacuoles and as
extravasated (Figure 1B
). There were 4 mitoses per 10
high power fields and there was no necrosis (Figure 2
immunohistochemistry, tumor cells were stained positively
with CD34 (diluted 1:400, Thermo Scientific, Fremont,
CA) and CD31 (diluted 1:100, Thermo Scientific, Fremont,
CA) and they were negatively stained with TFE3 (diluted
1:50, ZETA Corporation, California, USA), cytokeratin
(diluted 1:100, Thermo Scientific, Fremont, CA) (Figure 3
), SMA (diluted 1:800, Thermo Scientific, Fremont, CA),
EMA (diluted 1:600, Thermo Scientific, Fremont, CA),
S-100 (diluted 1:150, Thermo Scientific, Fremont, CA),
and HHV-8 (diluted 1:100, Thermo Scientific, Fremont,
CA), Ki67 proliferation index (diluted1:150, Thermo
Scientific, Fremont, CA) was 30% (Figure 4
). The patient
was evaluated as epithelioid hemangioendothelioma based
on the histomorphological and immunohistochemical
Click Here to Zoom
|Figure 1: Tumor cells including slightly pleomorphic oval or round vesicular nuclei and cytoplasmic vacuoles (black arrow), H&E x 200
(A). Numerous erythrocytes within some vacuoles (arrow head), H&E x 400 (B).
Click Here to Zoom
|Figure 2: There are two mitoses in one high power field (black
arrow), H&E x 400.
Click Here to Zoom
|Figure 4: Tumor cells with high proliferative index, Ki67 antibody,
Epithelioid hemangioendothelioma was described as
a bone and soft tissue vascular tumor, a subtype of
hemangioendothelioma by Weiss and Enzinger in 1982 12
Epithelioid hemangioendothelioma is usually localized in
soft tissues and extremities. It may be also localized in the
head and neck 13. Epithelioid hemangioendothelioma
rarely occurs in the oral cavity and only 31 cases have been
reported in the literature until the present day. The gingiva
is the most common location in the oral cavity, followed
by the tongue, and the maxillary and buccal mucosa,
respectively 6,7. Epithelioid hemangioendothelioma may
be seen at any age. However, it is more commonly observed
in the middle ages and affects both genders approximately
at equal rates 1. Clinically, it usually occurs as a painful
mass 2. Our case was a 55-year-old male patient who
presented to the clinic with a painless mass.
Neoplastic endothelial cell proliferation, eosinophilic
vacuolated cytoplasm, and occasionally fusiform cells are
observed as the characteristic microscopic features 13. In
most cases, there is almost no mitotic activity in the tumor.
The microscopic differential diagnosis of epithelioid
hemangioendothelioma is performed by taking carcinoma,
epithelioid angiosarcoma, melanoma, and angioleiomyoma
into consideration 8,13. Epithelioid hemangioendothelioma
may be confused with carcinoma with its high
cellularity and mitotic activity 12. Immunohistochemically,
hemangioendothelioma cells are positive for CD34,
CD31, and vonWillebrand factor 14. Positive staining
with endothelial markers such as CD31, CD34, and Factor
VIII may be helpful in differentiating epithelioid hemangioendothelioma
from carcinoma 15. In addition, cytokeratin
is strongly positive in almost all carcinomas as well
as epithelioid angiosarcomas and epithelioid sarcomas.
However, approximately 25% of epithelioid hemangioendotheliomas
are cytokeratin and EMA positive, but this is weak and focally positive compared with epithelioid
sarcoma 2. Epithelioid angiosarcoma is expected to be
strongly positively stained with CD31, CD34, panCK, and
EMA during immunohistochemical examination. In our
case, tumor cells were stained positive with CD31 and CD34
whereas they were negatively stained with panCK and EMA
as the evidence of differentiation from carcinoma, epithelioid
sarcoma, and epitheloid angiosarcoma. Melanoma
was ruled out since it was S100 negative. Approximately,
one fourth of the epithelioid hemangioendothelioma cases
show mitotic activity (more than 1 mitosis at 10 high-power
fields), significant atypia, and necrosis 1. Cellular atypia,
areas of necrosis, a high rate of spindle cell proliferation,
and the presence of mitotic figures indicate higher aggressiveness
for the tumor 11. A 4/10 mitotic count per HPF
and a Ki67 proliferation activity index of 30% were detected
in our case. However, no necrosis or significant pleomorphism
was observed. Because of high mitotic activity and a
high Ki-67 proliferative index, our case was considered to
have an aggressive clinical course and close clinical followup
The treatment recommended for oral epithelioid
hemangioendothelioma was extensive surgical resection
followed by the regular follow-up 8.
In conclusion, only ten cases have been reported in the
tongue in the literature. Our case was the eleventh case, and
we aimed to report this case as a rare entity with an unusual
location. A consensus on diagnosis may not be established
by different pathologists in unusual cases. Therefore, it
would be important to report the cases with rarely seen
tumor localization in the literature.
CONFLICT of INTEREST
The authors declare no conflict of interest.
Concept: DSC, IES, EA, Design: DSC, IES, Data collection
or processing: DSC, ED, GSO, Analysis of Interpretation:
DSC, IES, ED, Literature search: DSC, IES, Writing: DSC,
IES, Approval: DSC, IES, ED, GSO.
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