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Bone: Epithelioid hemangioendothelioma with t(1;3)(p36;q25) WWRT1/CAMTA1

Written2014-06Andreas F Mavrogenis, Andrea Angelini, Costantino Errani, Pietro Ruggieri
First Department of Orthopaedics, Athens University Medical School, ATTIKON University Hospital, Athens, Greece (AFM); Istituto Ortopedico Rizzoli, Bologna, Italy (AA, CE, PR)

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TUMOUR:::VascularBoneID5357.txt ==> 5357 TUMOUR:::VascularBoneID5357.txtTUMOUR:::HaemangiomBoneID5358.txt ==> 5358 TUMOUR:::HaemangiomBoneID5358.txtTUMOUR:::BoneAngiosarcID5359.txt ==> 5359 TUMOUR:::BoneAngiosarcID5359.txt
ICD-Topo C400-C403,C408-C414,C418-C419 BONES & JOINTS
ICD-Morpho 9120/3 Hemangiosarcoma
Atlas_Id 5617
Phylum Bones::Epithelioid haemangioendothelioma
WHO/OMS Classification Bones
Other namesHemangiosarcoma
Hemangioendothelial sarcoma
Epithelioid angiosarcoma
Epithelioid sarcoma-like hemangioendothelioma
Pseudomyogenic hemangioendothelioma
Note Vascular tumors of bone range from benign hemangioma to highly malignant angiosarcoma. They are composed of tumor cells forming vascular spaces. In 1943, Stout defined the diagnostic criteria for malignant vascular tumors, which he named hemangioendothelioma. Since 1994, the use of the term "hemangioendothelioma" referring to vascular tumors of bone has decreased due to the need of a more accurate classification. According to the WHO Classification of Tumors of Soft Tissue and Bone and the ISSVA classification, the term "hemangioendothelioma" connotes intermediate malignancy, except in the context of epithelioid hemangioendothelioma, which is described as a distinct entity and classified as malignant.
We consider the name epithelioid hemangioendothelioma of bone for low-grade malignant endothelial vascular neoplasms of bone with tumor cells showing endothelial differentiation, and a biologic behavior between that of hemangioma and angiosarcoma.

Clinics and Pathology

TUMOUR:::BoneTumorID5143.txt ==> 5143 TUMOUR:::BoneTumorID5143.txt GENE:::GC_VIM.txt ==> 42791 GENE:::GC_VIM.txtGENE:::GC_PECAM1.txt ==> 41689 GENE:::GC_PECAM1.txtGENE:::GC_CD34.txt ==> 975 GENE:::GC_CD34.txt
Note Pathogenesis unclear. Highly malignant vascular tumors of bone (angiosarcomas) may arise at sites of prior radiation.
Epidemiology Epithelioid hemangioendothelioma of bone account for less than 1% of malignant bone tumors. It may occur at any age, although approximately half of the cases tend to occur during the second and third decades of life. Males and females are approximately equally affected. The tumors show a wide skeletal distribution affecting the long tubular bones of the extremity and the axial skeleton, mainly the spine. The lower extremities are predominantly affected, with more than half of the lesions located in the tibia or femur; spinal lesions account for less than 10% of the cases. Approximately one third are multicentric within a bone or multifocal, within multiple bones with lesions randomly distributed throughout the skeleton or clustered in an anatomic region, such as a single extremity. However, the distinction between multifocal and metastatic disease is not clear. In general multifocal disease is thought to be limited to a specific anatomic region (i.e., bones of the same limb) with variable involvement of individual osseous elements. Thus it is debatable whether disease in the femur and cervical spine may be considered multifocal, as opposed to metastatic given that this tumor has capacity of metastasizing hematologically. However, when disease is located in the distal femur or patella, is easier to consider it multifocal.
Clinics Clinical symptoms include pain and possible association with a palpable tumor mass. Neurological symptoms may occur in patients with spinal involvement. Tumor growth may be rapid or slow, and infiltrative.

The imaging appearance of epithelioid hemangioendothelioma of bone is non-specific. The tumors are purely lytic, poorly marginated with varying degrees of peripheral sclerosis. A soft tissue mass is often associated with less well differentiated tumors. Clustering of multifocal lesions in a single anatomic location suggests the diagnosis of a vascular neoplasm.

Figure A: Sagittal T2-weighted magnetic resonance imaging of the sacrum shows osteolysis and destruction of the coccyx with anterior soft tissue mass. Biopsy showed epithelioid hemangioendothelioma of the coccyx. Figure B: Sagittal T1-weighted magnetic resonance imaging of the thoracic spine of a patient with recurrent epithelioid hemangioendothelioma of the T3 vertebra.
Pathology Gross pathology: Macroscopically, epithelioid hemangioendothelioma of bone tends to be firm and tan-white. The tumor can erode the cortex and extend into the soft tissue.
Micropathology: Microscopically, the tumor is composed of anastomosing cords, solid nests, and strands of endothelial cells that may sometimes form narrow vascular channels. The small capillary-sized tumor vessels can mimic small reactive vessels of granulation tissue. The epithelioid cells tend to have eosinophilic cytoplasm which may show vacuolization and sometimes signet ring-like appearance. The connective tissue stroma shows significant myxoid and hyalinized appearance. The nuclei of the neoplastic cells show varying degrees of pleomorphism and anaplasia.
Although many variants of hemangioendothelioma have been reported, the striking features of growth of epithelioid hemangioendothelioma of bone are the formation of atypical endothelial cells (marked nuclear atypia, mitotic activity, spindling of cells and necrosis) arranged in cords, in greater numbers than required to line the vessels with a simple endothelial membrane, and the formation of vascular tubes with a delicate framework of reticulin fibers with a marked tendency for their lumens to anastomose. On hematoxylin and eosin stains the neoplastic epithelioid endothelial cells are embedded in a hyalinized (deep pink) or chondroid-like (light blue) matrix. No tumor should be considered an epithelioid hemangioendothelioma of bone unless these criteria are present.
Immunophenotype: The endothelial cells uniformly express vimentin and many cells stain with antibodies to Factor VIII, CD31, CD34, and Ulex Europaeus. Epithelioid malignancies may also express cytokeratins and EMA.
Ultrastructure: The endothelial cells contain Weibel-Palade bodies, but are generally difficult to find in poorly differentiated tumors. Cytoplasmic filaments are abundant.
Figure C: Photomicrograph (stain, hematoxylin and eosin; original magnification, 10x) shows epithelioid cytomorphology with variably solid or vasoformative architecture and tumoral cells with large, pleomorphic and mildy hyperchromatic nuclei with evident nucleoli. Vascular cavities are variable and matted with neoplastic endothelial cells. Figure D: Photomicrograph (stain, hematoxylin and eosin; original magnification, 20x) shows blood filled cavities of different caliber rimmed by plump endothelium with epithelioid appearance. CD31 staining of the endothelium of the tumoral vessels is typically cytoplasmic.
Treatment Surgical: Patients with epithelioid hemangioendothelioma of bone may be cured by surgery, with or without other treatments such as chemotherapy, radiation therapy and embolization. A possible major role for wide surgery should be considered for these tumors whenever this choice does not involve high morbidity or poor functional results.
Radiation therapy: Adjuvant radiation therapy is advocated to decrease the risk of local recurrence. The risk for postradiation complications should be considered.
Embolization: As a vascular tumor the potential for intraoperative blood loss is significant. To lessen this complication, patients should have an angiographic evaluation and selective embolization when feasible.
Evolution Outcome: The reported local recurrence rate is up to 13%. Wide tumor resection has been related with a lower risk for local recurrence; however, a statistically significantly higher survival to local recurrence has not been shown in multivariate analysis. A median survival of 21 months, a 5-year survival of approximately 33%, and a metastatic rate of up to 31% has been reported. It is difficult to establish correctly which patient had bone metastasis and which patient had progression of the disease in the multifocal form. In the absence of a genetic analysis, patients with unifocal tumors that developed bone lesions after treatment should probably be considered as tumor progression in multifocal form.
Prognosis The histological degree of differentiation as evaluated pathologically by the histological pattern of the tumor and the cytologic atypia of the neoplastic endothelial cells, and the presence of unifocal or multifocal tumor are the most important prognostic factors. The survival advantage for the patients with multifocal tumors may in part be related to the fact that multifocal tumors show better differentation. Conventionally, multifocal disease in a tumor with atypia would be considered a metastatic deposit, whereas when it occurs in tumors with entirely benign features it is considered a multifocal process. Additionally, tumor location in the axial skeleton and limb girdles probably precludes good prognosis because it is difficult to obtain adequate surgery, or multifocal tumors with poor outcome represent tumors with biologic behavior closer to angiosarcoma.


Note Two epithelioid hemangioendotheliomas have shown an identical chromosomal translocation involving chromosomes 1 and 3.
GENE:::WWTR1ID44545ch3q25.txt ==> 44545 GENE:::WWTR1ID44545ch3q25.txtGENE:::CAMTA1ID908ch1p36.txt ==> 908 GENE:::CAMTA1ID908ch1p36.txt

Genes involved and Proteins

Note Recent identification of WWTR1-CAMTA1 fusion provides a powerful diagnostic tool that can be used to distinguish an epithelioid hemangioendothelioma of bone from a hemangioendothelioma. However, genetic hallmarks of hemangioendothelioma are still under investigation.


Hemangioendothelioma of the spine.
Aflatoon K, Staals E, Bertoni F, Bacchini P, Donati D, Fabbri N, Boriani S, Frassica FJ.
Clin Orthop Relat Res. 2004 Jan;(418):191-7.
PMID 15043114
Surgical treatment and results of 62 patients with epithelioid hemangioendothelioma of bone.
Angelini A, Mavrogenis AF, Gambarotti M, Merlino B, Picci P, Ruggieri P.
J Surg Oncol. 2014 Jun;109(8):791-7. doi: 10.1002/jso.23587. Epub 2014 Mar 18.
PMID 24643837
Hemangioendothelioma of bone: a study of 29 cases.
Campanacci M, Boriani S, Giunti A.
Cancer. 1980 Aug 15;46(4):804-14.
PMID 7397643
Vascular bone tumors: a proposal of a classification based on clinicopathological, radiographic and genetic features.
Errani C, Vanel D, Gambarotti M, Alberghini M, Picci P, Faldini C.
Skeletal Radiol. 2012 Dec;41(12):1495-507. doi: 10.1007/s00256-012-1510-6. Epub 2012 Sep 21. (REVIEW)
PMID 22993209
A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites.
Errani C, Zhang L, Sung YS, Hajdu M, Singer S, Maki RG, Healey JH, Antonescu CR.
Genes Chromosomes Cancer. 2011 Aug;50(8):644-53. doi: 10.1002/gcc.20886. Epub 2011 May 16.
PMID 21584898
Vascular tumors of bone: A study of 17 cases other than ordinary hemangioma, with an evaluation of the relationship of hemangioendothelioma of bone to epithelioid hemangioma, epithelioid hemangioendothelioma, and high-grade angiosarcoma.
Evans HL, Raymond AK, Ayala AG.
Hum Pathol. 2003 Jul;34(7):680-9.
PMID 12874764
Subperiosteal hemangioendothelioma of the femur.
Gupta A, Saifuddin A, Briggs TW, Flanagan AM.
Skeletal Radiol. 2006 Oct;35(10):793-6. Epub 2006 Jan 19.
PMID 16421750
Spinal epithelioid hemangioendothelioma with epithelioid angiosarcomatous areas.
Hisaoka M, Okamoto S, Aoki T, Yokoyama K, Hashimoto H.
Skeletal Radiol. 2005 Nov;34(11):745-9. Epub 2005 May 5.
PMID 15877225
Pseudomyogenic hemangioendothelioma: a distinctive, often multicentric tumor with indolent behavior.
Hornick JL, Fletcher CD.
Am J Surg Pathol. 2011 Feb;35(2):190-201. doi: 10.1097/PAS.0b013e3181ff0901.
PMID 21263239
Epithelioid hemangioendothelioma of bone.
Kleer CG, Unni KK, McLeod RA.
Am J Surg Pathol. 1996 Nov;20(11):1301-11.
PMID 8898834
The results of the application of special histological methods to the study of tumors.
Mallory FB.
J Exp Med. 1908 Sep 5;10(5):575-93.
PMID 19867151
Translocation t(1;3)(p36.3;q25) is a nonrandom aberration in epithelioid hemangioendothelioma.
Mendlick MR, Nelson M, Pickering D, Johansson SL, Seemayer TA, Neff JR, Vergara G, Rosenthal H, Bridge JA.
Am J Surg Pathol. 2001 May;25(5):684-7.
PMID 11342784
Primary Angiosarcoma of Bone: A Retrospective Analysis of 60 Patients From 2 Institutions.
Palmerini E, Maki RG, Staals EL, Alberghini M, Antonescu CR, Ferrari C, Ruggieri P, Mavrogenis A, Bertoni F, Cesari M, Paioli A, Marchesi E, Picci P, Ferrari S.
Am J Clin Oncol. 2013 Mar 4. [Epub ahead of print]
PMID 23466575
Tumors and tumor-like lesions of the bone: Imaging and pathology of specific lesions.
Resnick D, Kyriakos M, Greenway GD.
In: Resnick D, editor. Diagnosis of bone and joint disorders, 3rd edition. Philadelphia, PA: WB Saunders Co; 1995;3628-938.
Angiosarcoma. Pathology and genetics of tumours of soft tissue and bone.
Roessner A, Boehling T.
In: World Health Organization classification of tumours of soft tissue and bone. Fletcher CDM, Unni KK, Mertens F, editors. Lyon: IARC Press; 2002;322-3.
The histiocytoid hemangiomas. A unifying concept embracing several previously described entities of skin, soft tissue, large vessels, bone, and heart.
Rosai J, Gold J, Landy R.
Hum Pathol. 1979 Nov;10(6):707-30.
PMID 527967
Hemangio-endothelioma: A tumor of blood vessels featuring vascular endothelial cells.
Stout AP.
Ann Surg. 1943 Sep;118(3):445-64.
PMID 17858281
Epithelioid hemangioendothelioma of bone. A clinicopathologic, ultrastructural, and immunohistochemical study.
Tsuneyoshi M, Dorfman HD, Bauer TW.
Am J Surg Pathol. 1986 Nov;10(11):754-64.
PMID 2430475
Hemangioma, hemangiopericytoma, and hemangioendothelioma (angiosarcoma) of bone.
Unni KK, Ivins JC, Beabout JW, Dahlin DC.
Cancer. 1971 Jun;27(6):1403-14.
PMID 5088217
Hemangioendothelial sarcoma of bone.
Wold LE, Unni KK, Beabout JW, Ivins JC, Bruckman JE, Dahlin DC.
Am J Surg Pathol. 1982 Jan;6(1):59-70.
PMID 7200731


This paper should be referenced as such :
AF Mavrogenis, A Angelini, C Errani, P Ruggieri
Bone: Epithelioid hemangioendothelioma
Atlas Genet Cytogenet Oncol Haematol. 2015;19(2):150-154.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(1;3)(p36;q25) WWTR1/CAMTA1

External links

Mitelman database t(1;3)(p36;q25) [CaseList]     t(1;3)(p36;q25) [Transloc - MCList]   WWTR1/CAMTA1 Fusion - MCList]
arrayMap Topo ( C40,C41) arrayMap ((UZH-SIB Zurich)   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databaseWWTR1/CAMTA1[MCList]    WWTR1 (3q25.1) CAMTA1 (1p36.31)   t(1;3)(p36;q25)
TICdbWWTR1/CAMTA1    WWTR1 (3q25.1) CAMTA1 (1p36.31)
Disease databaseBone: Epithelioid hemangioendothelioma with t(1;3)(p36;q25) WWRT1/CAMTA1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed

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