Diagnosis -- YAP1::TFE3 rearranged epithelioid hemangioendothelioma

FINAL DIAGNOSIS

YAP1::TFE3 rearranged epithelioid hemangioendothelioma

DISCUSSION

YAP1::TFE3-rearranged hemangioendothelioma (EHE) is an extremely rare malignant vascular tumor that is distinct from its conventional counterpart. The latter is often characterized by WWTR1::CAMTA1 gene fusions. YAP1::TFE3-rearranged EHE shows a slight female predominance and occurs more commonly in young to middle-aged adults. Roughly half the cases present with multifocal disease. Morphologically, these tumors are composed of nests of epithelioid cells with voluminous, often brightly eosinophilic cytoplasm, with occasional vacuolization and prominent nucleoli. In contrast to conventional EHE, these tumors often show areas of vasoformation. By immunohistochemistry, the tumor cells are positive for vascular markers, including CD31 and ERG as well as TFE3. Cytokeratin expression is variable. Unlike their conventional counterparts, these tumors are consistently negative for CAMTA1 immunohistochemistry. Finally, patients with YAP1::TFE3 rearranged EHE has a more favorable outcome than those with WWTR1::CAMTA1 gene rearrangements, with overall 5-year survival being 86% versus 59%, respectively.

In conclusion, YAP1::TFE3-rearranged EHE is a rare malignant vascular tumor that appears to be distinct from conventional EHE in terms of its clinical, pathologic, and genetic characteristics.

REFERENCES

1. Rubin PB et al. Epithelioid hemangioendothelioma. In: WHO Classification of Tumours Editorial Board. Soft tissue and bone tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2020 [2022 10 10]. (WHO classification of tumours series, 5th ed.; vol. 3). Available from: https://tumourclassification.iarc.who.int/chapters/33.
2. Dermawan JK et al. YAP1-TFE3-fused hemangioendothelioma: a multi-institutional clinicopathologic study of 24 genetically-confirmed cases. Mod Pathol. 2021 Dec; 34(12):2211-2221.
3. Rosenbaum E et al. Prognostic stratification of clinical and molecular epithelioid hemangioendothelioma subsets. Mod Pathol. 2020 Apr; 33(4):591-602.

Contributed by Azfar Neyaz, MD, and Ivy John, MD