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

Uta Flucke*, Rob J. C. Vogels, Nicolas de Saint Aubain Somerhausen, David H. Creytens, Robert G. Riedl, Joost M. van Gorp, Anya N. Milne, Clement J. Huysentruyt, Marian A. J. Verdijk, Monique M. van Asseldonk, Albert J. H. Suurmeijer, Johannes Bras, Gabriele Palmedo, Patricia J. T. A. Groenen, Thomas Mentzel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

113 Citations (Web of Science)

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.
Original languageEnglish
Article number131
JournalDiagnostic Pathology
Volume9
DOIs
Publication statusPublished - 1 Jul 2014

Keywords

  • Epithelioid hemangioendothelioma
  • Vascular tumors
  • Soft tissue
  • Bone
  • Skin
  • Lung
  • Liver

Cite this