Clinicopathologic and radio-genomic insights into hepatic epithelioid hemangioma: An illustrated review

Epithelioid hemangioma (EH) of the liver is an exceptionally rare vascular neoplasm, with only one pathology-confirmed case previously reported. We describe the second such instance, and the first to incorporate detailed radiologic characterization and RNA sequencing. A 68-year-old man presented with hepatic masses, portal lymphadenopathy, and a lytic pubic lesion initially concerning for metastatic carcinoma. Liver biopsy demonstrated a vascular proliferation of hobnail endothelial cells within myxoid stroma, with associated hemorrhage, hemosiderin, and eosinophil-rich inflammation. Immunohistochemistry showed diffuse ERG and focal FOSB expression, weak TFE3 staining, and a low proliferative index, while CAMTA1 and HMB-45 were negative. Imaging revealed multifocal, mildly FDG-avid hepatic lesions with nodal and osseous involvement. Whole-transcriptome sequencing was negative for pathogenic fusions. These findings confirmed a diagnosis of EH, illustrating its capacity to mimic malignancy. This case highlights the diagnostic value of integrating radio-genomic analysis and underscores the need for comprehensive workup to distinguish EH from epithelioid hemangioendothelioma, angiosarcoma, and Kaposi sarcoma, entities with distinct prognostic and therapeutic implications.