[20] TFE3 Gene Rearrangements Define a Distinct Subtype of Epithelioid Hemangioendothelioma (EHE)

Cristina R Antonescu, Francois Le Loarer, Lei Zhang, Nursat Pathan, Ilan Weinreb, Meera Hameed, Christopher D Fletcher. Memorial Sloan-Kettering Cancer Center, New York, NY; Raritan Bay Medical Center, Raritan Bay, NJ; University Health Network and University of Toronto, Toronto, Canada; Brigham and Women's Hospital, Boston, MA

Background: Classic EHEs are characterized by epithelioid cells arranged in cords and single cells in a myxo-chondroid or sclerotic stroma, typically lacking well-formed vasoformative properties. At the genetic level they show recurrent t(1;3) translocation, resulting in WWTR1-CAMTA1 fusion gene, in the majority of cases, which can be used to exclude other epithelioid vascular tumors. In the course of WWTR1-CAMTA1 screening, we have encountered a fusion-negative subgroup that show distinctive morphologic features which were investigated for recurrent novel genetic abnormalities.
Design: WWTR1-CAMTA1 fusion-negative epithelioid vascular tumors, the morphology of which did not fit with either classic EHE or epithelioid hemangioma were selected for this study. Based on an index case showing strong TFE3 immunoreactivity, FISH analysis for TFE3 gene rearrangement was applied to the index case as well as to 4 additional cases. A control group, including 17 epithelioid hemangiomas, 9 pseudomyogenic (epithelioid sarcoma-like) HE and 3 high grade epithelioid angiosarcoma were also tested.
Results: TFE3 gene rearrangement was identified in 5 patients (3 males, 2 females, mean age 35 years), located in soft tissue (trunk, 2, head and neck, 1, extremity 1) and bone (vertebra, 1), but in none of the controls. The tumors were composed of epithelioid endothelial cells with abundant cytoplasm, ranging from pale-vacuolated to glassy-eosinophilic, with mild to moderate nuclear pleomorphism, but which lacked the usually greater anaplasia typically seen in angiosarcoma. They consistently showed well-formed vascular channels, in addition to a variably solid, nested or focally cord-like architecture. All tumors expressed endothelial markers (CD31 and/or ERG), as well as strong nuclear TFE3, but were negative for cytokeratin and HMB45.
Conclusions: We are reporting a novel subset of EHE of soft tissue and bone occurring in young adults which show TFE3 gene rearrangement associated with strong immunoreactivity for TFE3. The morphologic hallmark for these tumors is the voluminous eosinophilic cytoplasm with mild to moderate cytologic atypia and distinct vasoformative features.
Category: Bone & Soft Tissue

Monday, March 4, 2013 1:00 PM

Poster Session II # 1, Monday Afternoon


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