S5456 Hepatic Epithelioid Hemangioendothelioma With Lung Metastasis

Introduction: Hepatic epithelioid hemangioendothelioma (HEHE) is an exceptionally rare vascular liver malignancy with an incidence of 1–2 cases per million, highly variable prognosis, and no established treatment guidelines. Despite its rarity, HEHE is an accepted indication for orthotopic liver transplantation (OLT), even in select patients with limited extrahepatic disease. Case Description/Methods: A 45-year-old woman with metabolic dysfunction–associated steatotic liver disease (MASLD), obesity, type 2 diabetes, and hypertension presented with right upper quadrant pain. Laboratory testing showed anemia and elevated alkaline phosphatase, but otherwise normal liver function panel and unrevealing tumor markers including AFP, CA 19-9, and CEA. A contrast-enhanced computed tomography (CT) showed multiple hypoattenuating liver lesions on portal venous phase with relative hyperenhancement on delayed imaging, and MRI demonstrated >15 hepatic lesions with a targetoid pattern with no evidence of cirrhosis. Biopsy of the largest hepatic lesion revealed an epithelioid neoplasm positive for ERG and CAMTA1 on immunohistochemistry, confirming HEHE. PET/CT showed hypermetabolic liver lesions and bilateral pulmonary nodules with biopsy-confirmed metastatic hemangioendothelioma in the left upper lobe. Given that HEHE is a recognized indication for liver transplantation, even in selected patients with limited, controlled extrahepatic disease, she was conditionally approved for liver transplantation. However, her listing was temporarily deferred pending targeted optimization of her morbid obesity. She began systemic chemotherapy with pazopanib, a VEGF inhibitor with known activity against HEHE, in March 2025. She remains under active surveillance by a multidisciplinary care team, closely monitoring her metastatic disease status as she meets additional criteria required for transplantation. Discussion: In summary, this case highlights the diagnostic and therapeutic complexity of HEHE, underscoring the importance of high clinical suspicion, meticulous radiologic-pathologic correlation, and the critical role of CAMTA1 immunohistochemistry in diagnosing HEHE. Additionally, the case reflects the evolving view that carefully selected patients with metastatic HEHE may still benefit from liver transplantation. Further research is needed to define the role of systemic therapies, refine patient selection criteria, and establish standardized treatment protocols for HEHE.