Combined hepatocellular-cholangiocarcinoma: An update

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a tumour that exhibits both hepatocytic and biliary differentiation. Classical risk factors for hepatocellular carcinoma (HCC) seem to also predispose patients to the development of cHCC-CCA. The pathological definition of cHCC-CCA has significantly evolved over time. The last 2019 WHO classification highlighted that the diagnosis of cHCC-CCA should be primarily based on morphology using routine stainings, with additional immunostaining used to refine the identification of subtypes. Among them, intermediate cell carcinoma is recognised as a specific subtype, while cholangiolocellular carcinoma is now considered a subtype of iCCA. Increasing molecular evidence supports the clonal nature of cHCC-CCA and parallels its biphenotypic histological appearance, with genetic alterations that are classically observed in HCC and/or iCCA. That said, the morphological diagnosis of cHCC-CCA is still challenging for radiologists and pathologists, especially on biopsy specimens. Identification of cHCC-CCA's cell of origin remains an area of active research. Its prognosis is generally worse than that of HCC, and similar to that of iCCA. Resection with lymph node dissection is unfortunately the only curative option for patients with cHCC-CCA. Thus, there remains an urgent need to develop specific therapeutic strategies for this unique clinical entity. (c) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Automated summary

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a tumor with both hepatocytic and biliary differentiation, whose diagnosis is primarily based on morphology and immunostaining, with a prognosis worse than hepatocellular carcinoma and treatment limited to surgery.