Combined Hepatocellular-Cholangiocarcinoma (cHCC-CCA): A Rare Case of Biphenotypic Primary Liver Carcinoma in a Post-Hemicolectomy Patient

Combined Hepatocellular-Cholangiocarcinoma (cHCC-CCA) is a rare primary liver malignancy characterised by the presence of both hepatocytic and biliary epithelial differentiation within the same tumour and is associated with a poorer prognosis compared to Hepatocellular Carcinoma (HCC) or intrahepatic Cholangiocarcinoma (iCCA) alone. Accurate diagnosis is challenging, particularly in patients with a prior history of extrahepatic malignancy, where metastatic disease must be carefully excluded. We report the case of a 65-year-old male with a history of colonic adenocarcinoma treated by hemicolectomy and adjuvant chemotherapy in 2007, who remained disease-free for 18 years. In 2025, he presented with abdominal pain, and imaging revealed a solitary hepatic lesion in segment VI. Serum tumour markers demonstrated markedly elevated Alpha-Fetoprotein (AFP; 951 ng/mL), while Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 19-9 (CA19-9) levels were within normal limits. Given the prior history of Colorectal Carcinoma (CRC), metastatic disease was initially considered. Histopathological examination revealed a poorly differentiated malignant neoplasm with biphasic morphology. Immunohistochemical analysis showed hepatocytic differentiation with positivity for HepPar-1 and arginase-1, alongside cholangiocytic differentiation demonstrated by CK7 and CK19 expression. Markers associated with colorectal origin (CK20, CDX2, SATB2) were negative, effectively excluding metastatic CRC. Based on these findings, a final diagnosis of poorly differentiated classical combined hepatocellular–cholangiocarcinoma was rendered. This case underscores the critical role of comprehensive histopathological evaluation and targeted immunohistochemistry in establishing the diagnosis of cHCC-CCA. Early and accurate distinction from metastatic disease and other primary liver tumours is essential due to its distinct biology, aggressive behaviour, and adverse prognostic implications.