Combined Hepatocellular-Cholangiocarcinoma (cHCC-CCA): Bridging Pathology, Imaging, and Clinical Management in Oncology Practice - A Narrative Review

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer with epidemiological, diagnostic, and molecular features intermediate between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Imaging diagnosis is challenging due to overlapping characteristics with HCC and iCCA, and tumor markers lack specificity. Histological diagnosis relies on the coexistence of hepatocytic and cholangiocytic differentiation within the same tumor, while advances in AI-assisted genomic profiling offer promise for improved classification and prognosis. Therapeutic strategies for localized disease remain unclear, with hepatic resection being the main curative option and liver transplantation showing inferior outcomes. For advanced disease, evidence is limited and inconclusive, although immunotherapy and targeted therapies show emerging potential. This narrative review consolidates and synthesizes current knowledge on cHCC-CCA aggregating key insights into this complex and challenging malignancy.