Care should be taken to identify such cells in limited biopsies; immunohistochemistry for CAMTA1, a specific and sensitive marker for EHE, can be confirmatory.
A WWTR1-CAMTA1 fusion is present in most classic epithelioid hemangioendothelioma, regardless of their clinical behavior, suggesting that additional genetic abnormalities might be responsible in driving a more aggressive biology.
We point out the telltale immunophenotypes: angiolymphoid hyperplasia with eosinophilia and EH (FOS-B/others negative), PM-HAE (FOS-B/AE1/AE3/others negative), epithelioid hemangioendothelioma (CAMTA-1 or TFE-3/others negative).
Characterization of the genetics of EHE is important because targeted therapies toward products of the specific WWTR1-CAMTA1 gene fusion may have an impact in the near future.
The 10% of EHEs that lack the TAZ⁻CAMTA1 fusion instead have a fusion of Yes-associated Protein (YAP) and Transcription Factor E3 (TFE3) genes (YAP-TFE3).
Thus, we undertook a molecular analysis of six samples from two patients with multicentric hepatic EHE to test our hypothesis that the presence of identical breakpoints in WWTR1 and CAMTA1 support the monoclonal nature of multifocal EHE.
The chimeric WWTR1/CAMTA1 transcription factor may represent a therapeutic target for EHE and offers the opportunity to shed light on the functions of two poorly characterized proteins.
Our results demonstrate the presence of a WWTR1-CAMTA1 fusion in all EHE tested from bone, soft tissue, and visceral location (liver, lung) in keeping with a unique and specific pathological entity.