Epithelioid Hemangioendothelioma: clinicopathologic, immunhistochemical, and molecular genetic analysis of 39 cases
1 Department of Pathology, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
2 Jules Bordet Institute, Brussels, Belgium
3 Department of Pathology, Ghent University Hospital, Ghent, Belgium
4 Department of Pathology, Maastricht University Medical Center, Maastricht, The Netherlands
5 Department of Pathology, Diakonessenhuis Utrecht, Utrecht, The Netherlands
6 Laboratory of Pathological Anatomy and Medical Microbiology (PAMM), Eindhoven, The Netherlands
7 Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
8 Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
9 Dermatopathology Bodensee, Friedrichshafen, Germany
Diagnostic Pathology 2014, 9:131 doi:10.1186/1746-1596-9-131Published: 1 July 2014
Epithelioid hemangioendothelioma is a malignant, often indolent vascular tumor which occurs at various anatomic sites. Based on a reciprocal translocation t (1;3)(p36;q25), a consistent WWTR1-CAMTA1 fusion gene has been found. An alternate YAP1-TFE3 fusion has been detected in a small and distinct subset of cases.
Thirty-nine tumors, from 24 females and 15 males with an age range 9–85 years, were located in soft tissue (head and neck , trunk , upper extremities , lower extremities , mediastinal , and paratesticular ), lymph node (1), breast (1), skin (2), bone (6), lung (7), and liver (2). The cases were investigated using a panel of immunohistochemical markers. The aforementioned fusion-genes were examined using RT-PCR and/or FISH in order to validate their diagnostic value.
Follow-up available for 17 patients ranged from 3 months to 7 years (median interval 1.5 years). Eleven patients were alive without disease, 2 patients were alive with disease after 1.5 and 2 years, respectively. Four patients died of disease after 4 months (n = 1), 5 months (n = 2), and 1.5 years (n = 1).
The size, known for 30 lesions, was >3 cm in 9 of them. Histologically, all lesions had classical features, at least focally. Four tumors counted >3 mitoses/50 HPF.
Immunohistochemically, all cases tested stained positive for ERG (21), FLI1 (5) and CD31 (39). CD34 and D2-40 positivity was seen in 81% and 71% of the examined cases, respectively. 11/35 cases expressed pan-keratin and 6/20 cases CK8.18. TFE3 showed a nuclear reaction in 21/24 cases, irrespective of TFE3 rearrangement.
Molecular genetically, 35/35 cases revealed one of the fusion genes by FISH and/or RT-PCR with WWTR1-CAMTA1 in 33 cases and YAP1-TFE3 in 2 cases.
These results demonstrate the high diagnostic value of FISH and RT-PCR in detecting the fusion genes of EHE. The immunohistochemical utility of TFE3 appears questionable in this study.
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