epithelioid hemangioendothelioma

Definition: Epithelioid hemagioendothelioma (EHE) is a rare vascular tumor with an intermediate biological behavior between hemangioma and angiosarcoma.

Images

 Epithelioid hemagioendothelioma (EHE)

• https://twitter.com/bestpathologist/status/701967928929857537
• https://twitter.com/TexPathol/status/1241696353182416896

 hepatic EHE

• https://twitter.com/mariaramir/status/718561174363709440
• https://twitter.com/AdamGomezMD/status/817021880771047428
• https://twitter.com/HongDXiao/status/852960758606446592

Epithelioid hemangioendothelioma (EHE) is a rare vascular soft tissue tumor of intermediate malignancy. Although initially described as most common in the soft tissues of the extremities, other locations are possible, namely bone.

EHE was first described by Weiss and Enzinger in 1982 as a rare vascular lesion with an epithelioid appearance.

The tumor is composed of a discrete population of epithelioid endothelial cells arranged to resemble primitive capillaries with an intermediate biological behavior between hemangioma and angiosarcoma.

EH represents 1% of all vascular neoplasms and is locally aggressive.

Although initially described as being most common in the soft tissues of the extremities, other reported sites of occurrence include the liver, lung, breast, meninges, brain and bones.

There seems to be no gender predilection, although some authors consider it to be more frequent in males. The highest incidence occurs in the third and fourth decades.

Recently a rare association with neurofibromatosis type I has been
reported.

Macroscopy

On gross pathology examination, EHE present as reddish-brown lobulated masses, well demarcated with irregular scalloped borders and a bright
red hemorrhagic appearance.

Microscopy

Microscopically, the tumor is characterized by anastomosing cords, solid nests, or short strands of round to slightly spindled eosinophilic neoplastic endothelial cells embedded in a chondroid-like or hyalinized stroma.

Rarely large and distinct vascular channels are identified in the center of the tumor, as contrasted with the periphery of the lesion, and mitotic activity seldom is identified in these tumors.

Immunochemistry

Immunohistochemical analysis reveals that the tumor cells are positive for vimentin and endothelial markers such as factor VIII-related antigen, ulex
europaeus lectin, CD31 and CD349.

Molecular biology

 WWTR1-CAMTA1 fusion gene

• translocation t(1;3)(p36.3;q25) (1p36 and 3q25) (11342784)

 translocation t(7;22) (8976367)

 TFE3 rearrangements (26840265)

• TFE3-associated epithelioid hemangioendothelioma

Localization

 hepatic epithelioid hemangioendothelioma (2596622, 6088383, 2661410)
 epithelioid hemangioendothelioma of the bone (8898834, 2430475)
 cutaneous epithelioid hemangioendothelioma (9130982)
 soft tissues epithelioid hemangioendothelioma (9130982, 8067508)
 cerebral epithelioid hemangioendothelioma (8651350)
 penile epithelioid hemangioendothelioma (15087672)
 thyroid epithelioid hemangioendothelioma (27026033)

 vascular epithelioid hemangioendothelioma

• epithelioid hemangioendothelioma of the superior vena cava
• epithelioid hemangioendothelioma of the inferior vena cava

Variants

 epithelioid sarcoma-like hemangioendothelioma (12502927)

Differential diagnosis

  vascular tumors

• hemangioendotheliomas
• reactive angioendotheliomatosis

 CD34+ tumors
 epithelioid tumors / epithelioid cell tumors
 metastasis of an atrial myxoma (8279623)

See also

 hemangioendotheliomas
 vascular tumors

Open references

 Epithelioid hemangioendotheliomas with TFE3 gene translocations are compossible with CAMTA1 gene rearrangements. Lee SJ, Yang WI, Chung WS, Kim SK. Oncotarget. 2016 Feb 16;7(7):7480-8. doi : 10.18632/oncotarget.7060 PMID: 26840265 (Free)

 Epithelioid hemangioendothelioma presenting as a vertebral fracture. Neves N, Lima-Rodrigues F, Ribeiro-Silva M, Cacho-Rodrigues P, Eloy C, Paiva ME, Pinto R. Acta Reumatol Port. 2010 Jul-Sep;35(3):370-4. PMID: 20975643 [Free]

References

 Fujii T, Zen Y, Sato Y, Sasaki M, Enomae M, Minato H, Masuda S, Uehara T, Katsuyama T, Nakanuma Y. Podoplanin is a useful diagnostic marker for epithelioid hemangioendothelioma of the liver. Mod Pathol. 2008 Feb;21(2):125-30. PMID: 18084256

 Scoazec JY, Degott C, Reynes M, Benhamou JP, Feldmann G. Epithelioid hemangioendothelioma of the liver: an ultrastructural study. Hum Pathol. 1989 Jul;20(7):673-81. PMID: 2661410

 Ishak KG, Sesterhenn IA, Goodman ZD, Rabin L, Stromeyer FW. Epithelioid hemangioendothelioma of the liver: a clinicopathologic and follow-up study of 32 cases. Hum Pathol. 1984 Sep;15(9):839-52. PMID: 6088383

 Weiss SW, Enzinger FM. Epithelioid hemangioendothelioma: a vascular tumor often mistaken for a carcinoma. Cancer. 1982 Sep 1;50(5):970-81. PMID: 7093931

 Weiss SW, Goldblum JR. Epithelioid hemangioendothelioma: vascular tumors of intermediate malignancy. In: Weiss SW, Goldblum JR, eds. Enzinger and Weiss’s soft tissue tumors. Fifth edition ed: Mosby Elsevier; 2007:p. 891-916.

 O’Hara CD, Nascimento AG. Endothelial lesions of soft tissues: a review of
reactive and neoplastic entities with emphasis on low-grade malignant
("borderline") vascular tumors. Adv Anat Pathol. 2003;10:69-87.

 Ignacio EA, Palmer KM, Mathur SC, Schwartz AM, Olan WJ. Epithelioid
hemangioendothelioma of the lower extremity. Radiographics. 1999;19:531-7.

 Charette S, Nehler MR, Whitehill TA, Gibbs P, Foulk D, Krupski WC.
Epithelioid hemangioendothelioma of the common femoral vein: Case report
and review of the literature. J Vasc Surg. 2001;33:1100-3.

 Tayeb T, Bouzaiene M. [Epithelioid hemangioendothelioma mimicking an
occipital artery aneurysm]. Rev Stomatol Chir Maxillofac. 2007;108:451-4.

 Scordi-Bello IA, Snyder A, Schwartz M, Fallon JT. Intravascular epithelioid
hemangioendothelioma of the inferior vena cava: case report of an unusual
and unpredictable vascular tumor. Cardiovasc Pathol. 2009;18:243-6.

 Ferretti GR, Chiles C, Woodruff RD, Choplin RH. Epithelioid
hemangioendothelioma of the superior vena cava: computed tomography
demonstration and review of the literature. J Thorac Imaging. 1998;13:45-8.

 Mentzel T, Beham A, Calonje E, Katenkamp D, Fletcher CD. Epithelioid
hemangioendothelioma of skin and soft tissues: clinicopathologic and
immunohistochemical study of 30 cases. Am J Surg Pathol. 1997;21:363-74.

 Fenniche S, Benmously R, Marrak H, Khayat O, Ben Ammar F, Debbiche A,
Ben Ayed M, Mokhtar I. [Cutaneous epithelioid hemangioendothelioma.]. Ann Dermatol Venereol. 2004;131:818-21.

 Weiss SW, Goldblum JR. Leiomyosarcoma. In: Weiss SW, Goldblum JR, eds. Enzinger and Weiss’s soft tissue tumors. Fifth edition ed: Mosby Elsevier;
2007:p. 545-581.

 Zhao J, Roth J, Bode-Lesniewska B, Pfaltz M, Heitz PU, Komminoth P.
Combined comparative genomic hybridization and genomic microarray for
detection of gene amplifications in pulmonary artery intimal sarcomas and
adrenocortical tumors. Genes Chromosomes Cancer. 2002;34:48-57.
13. Palsson B. Epitheloid hemangioendothelioma. Acta Oncol. 1999;38:659-61.

 Epithelioid hemangioendothelioma of the facial bone. Bottini DJ, Gentile P, Ascenzi P, Galante V, Ricci A, Cervelli V. J Craniofac Surg. 2010 Nov;21(6):1994-6. PMID: 21119482

 Epithelioid hemangioendothelioma of the bone and intestinal infarction: an unusual association. Arena V, Pennacchia I, Carbone A, Vecchio FM. Colorectal Dis. 2011 Apr;13(4):e69-70. PMID: 21054745

 Weiss SW, Goldblum JR (eds). Hemangioendothelioma: vascular tumors of intermediate malignancy. In: Enzinger and Weiss’s Soft Tissue Tumors. Ed 4. St. Louis:Mosby 2001;891-915.

 Dorfman HD, Steiner GC, Jaffe HC. Vascular tumors of bone. Hum Pathol 1975;3:349-376.

 Boutin RD, Spaeth HJ, Mangalik A, Sell JJ. Epithelioid hemangioendothelioma of bone. Skeletal Radiol 1996;25:391-395.

 Rosai J, Gold J, Landy R. The histiocytoid hemangiomas. A unifying concept embrassing several previously described entities of skin, soft tissue, large vessels, bone, and heart. Hum Pathol 1979;10:707-730.

 Bevelaqua FA, Valensi Q, Hulnick D. Epithelioid hemangioendothelioma: A rare tumor with variable prognosis presenting as a pleural effusion. Chest
1988;93:665-666.

 Dietze O, Davies SE, Williams R, Portmann B. Malignant epithelioid hemangioendothelioma of the liver: A clinicopathological and histochemical study of 12 cases. Histopathology 1989;15:225-237.

 Chow LT, Chow W, Fong DT. Epithelioid hemangioendothelioma of the brain. Am J Surg Pathol 1992;16: 619-625.

 Larsson SE, Lorentzon R, Bouquist L. Malignant hemangioendothelioma of the bone. J Bone Joint Surg Am 1975;57:84-89.

 Themistocleous GS, Papagelopoulos PJ, Petraki KD, Stilianessi EV, Partsinevelos AA, Sapkas GS. A 23-yearold woman with complete paraplegia and anesthesia below the T8 level. Clin Orthop Rel Res 2005;430:258-265.

 Wold LE, Unni KK, Beabout JW, Ivins JC, Bruckman JE, Dahlin DC. Hemangioendothelial sarcoma of bone. Am J Surg Pathol. 1982;6:59-70.

 Tsuneyoshi M, Dorfman HD, Bauer TW. Epithelioid hemangioendothelioma of bone: a clinicopathologic, ultrastructural, and immunohistochemical study. Am J Surg Pathol 1986;10:754-764.

 Reis C, Carneiro E, Fonseca J, et al. Epithelioid hemangioendothelioma
and multiple thoraco-lumbar lateral meningoceles: two rare pathological entities in a patient with NF-1. Neuroradiol 2005;47:165-169.

 Aflatoon K, Staals E, Bertoni F, et al. Hemangioendothelioma of the spine. Clin Orthop 2004;418:191-197.

 Weiss SW, Enzinger FM. Epithelioid hemangioendothelioma: a vascular tumor often mistaken for a carcinoma. Cancer 1982;50:970-981.

 Tsuji M, Ozaki T, Tsutsumi A. Epithelioid hemangioendothelioma with osteoclast-like giant cells. Pathol Res Pract 2002;198:501-505.

 Campanacci M, Boriani S, Giunti A. Hemangioendothelioma of bone: a study of 29 cases. Cancer 1980;46:804-814.

 Aquilina K, Lim C, Kamel MH, Marks CJ, O’Sullivan MG, Keohane C. Epithelioid hemangioendothelioma of the spine. J Neurosurg Spine 2005;3:393-399.

 Ranty ML, Michot C, Le Pessot F, Simonet J, Defives T, Metayer J. Hémangiome épithélioide osseux récidivant. Ann Pathol 2003;23:173-176.

 Chau YP, Chan ACL, Wong CC. Lytic lesion in a vertebra of a 17-year-old adolescent girl. Arch Pathol Lab Med 2001;125:1611-1612.