Molecular characterization of epithelioid haemangioendotheliomas identifies novel WWTR1- CAMTA1 fusion variants.

Aims Epithelioid haemangioendothelioma ( EHE) is a malignant vascular neoplasm. Subsets have been characterized previously by translocations resulting in either WWTR1- CAMTA1 or YAP1- TFE3 fusion. We sought to develop molecular and immunohistochemical ( IHC) assays to aid in the diagnosis and characterization of EHE. Methods and results Fifty-two formalin-fixed, paraffin-embedded ( FFPE) cases diagnosed between 2002 and 2014 were retrieved from the pathology files of our institutions. Reverse transcription-polymerase chain reaction ( RT- PCR) assays were optimized to detect WWTR1- CAMTA1 and YAP1- TFE3 fusion transcripts in FFPE tissue and transcription factor E3 ( TFE3) protein accumulation was examined by immunohistochemistry ( IHC). RNA was extracted from 33 adequate samples, with more recent cases providing a greater yield of high quality RNA. Fourteen of 18 informative cases were positive for WWTR1- CAMTA1 fusion transcripts, four of which showed higher-grade cytological features termed by some as 'malignant EHE'. Novel in-frame fusion transcripts were identified in four cases by direct sequencing. IHC revealed variable nuclear TFE3 staining in six of 17 cases; three with patchy staining showed WWTR1- CAMTA1 fusion. One of 18 informative cases was positive for YAP1- TFE3 fusion and showed strong nuclear TFE3 staining by IHC. Conclusions This study confirms the high incidence of WWTR1- CAMTA1 and YAP1- TFE3 rearrangements in EHE and indicates that the staining pattern for TFE3 IHC is critical for specificity. [ABSTRACT FROM AUTHOR]