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. 2014 Jul 1:9:131.
doi: 10.1186/1746-1596-9-131.

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

Uta Flucke  1 , 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
Affiliations

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

Uta Flucke et al. Diagn Pathol. .

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.

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

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Figures

Figure 1
Figure 1
Case 6 showed solid areas without a myxohyaline stroma in addition to the classical morphological features (lower left).
Figure 2
Figure 2
Striking nuclear atypia was seen in approximately 30% of the cases (Case 14).
Figure 3
Figure 3
More vasoformative structures and nuclear atypia was present in Case 8 which harbored a YAP1-TFE3 fusion.
Figure 4
Figure 4
ERG was positive in all cases tested.
Figure 5
Figure 5
CD31 was strongly expressed in 38/39 cases.
Figure 6
Figure 6
TFE3 showed a nuclear reaction in cases with a WWTR1-CAMTA1 fusion.
Figure 7
Figure 7
FISH identified a fusion of WWTR1-CAMTA1.
Figure 8
Figure 8
Sequencing of the RT-PCR product shows an in-frame fusion between exon 4 of WWTR1 and exon 8 of CAMTA1 in the chimeric transcript in 13 cases.
Figure 9
Figure 9
YAP1 exon1 was fused to TFE3 exon 4 in two cases (ABI sequence).
See this image and copyright information in PMC

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