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Epithelioid Hemangioendothelioma: clinicopathologic, immunhistochemical, and molecular genetic analysis of 39 cases

Uta Flucke1*, Rob JC Vogels1, Nicolas de Saint Aubain Somerhausen2, David H Creytens3, Robert G Riedl4, Joost M van Gorp5, Anya N Milne5, Clement J Huysentruyt6, Marian AJ Verdijk1, Monique M van Asseldonk1, Albert JH Suurmeijer7, Johannes Bras8, Gabriele Palmedo9, Patricia JTA Groenen1 and Thomas Mentzel9

Author Affiliations

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

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Diagnostic Pathology 2014, 9:131  doi:10.1186/1746-1596-9-131

Published: 1 July 2014

Abstract

Background

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.

Methods

Thirty-nine tumors, from 24 females and 15 males with an age range 9–85 years, were located in soft tissue (head and neck [8], trunk [5], upper extremities [3], lower extremities [2], mediastinal [1], and paratesticular [1]), 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.

Results

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.

Conclusions

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.

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4010279141259481 webcite

Keywords:
Epithelioid hemangioendothelioma; Vascular tumors; Soft tissue; Bone; Skin; Lung; Liver