A Contemporary Approach to Diagnosis and Treatment of Combined Hepatocellular-Cholangiocarcinoma

Purpose of Review To provide updates on terminology, epidemiology, diagnosis, and treatment of combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Recent Findings cHCC-CCAs are tumors that in the same nodule contain a variable degree of HCC and CCA components with a transition zone. cHCC-CCAs develop in cirrhotic and non-cirrhotic livers like and is associated with poor outcomes. Mutations in TP53 , TERT promoter, and ARID1A are the most common genetic aberrations in cHCC-CCA. Fusion gene PTMS-AP1G1 is unique for cHCC-CCA. A biopsy is required for diagnosis. Surgical resection remains treatment of choice, while liver transplantation for early cHCC-CCA is associated with favorable outcomes. Gemcitabine-based therapy shows benefits for advanced cHCC-CCA. Summary cHCC-CCAs are a heterogeneous group of primary liver cancers with unique biological behavior. Multicenter studies are required for a molecular analysis to inform novel therapeutic approaches, and understand epidemiology and benefits of liver transplantation, liver-directed, and targeted therapies for this rare aggressive cancer.