Combined hepatocellular-cholangiocarcinoma: An update.

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Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a tumor that exhibits both hepatocytic and biliary differentiation. Classical risk factors of hepatocellular carcinoma (HCC) seem to also predispose to the development of cHCC-CCA. The pathological definition of cHCC-CCA has significantly evolved over time. The last 2019 WHO classification highlighted that cHCC-CCA diagnosis should be primarily based on morphology using routine stainings supported by additional immunostainings and refined the subtypes. Among them, the "intermediate cell carcinoma" is recognized as a specific subtype, and the "cholangiolocellular" subtype is now considered as a subtype of iCCA. Increasing molecular evidence supports the clonal nature of cHCC-CCA and molecular profile parallels its biphenotypic histological appearance, with genetic alterations that are classically observed in HCC and/or iCCA. Identification of the originating cell of cHCC-CCA remains an active research. The overall trend for its prognosis is to be 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. Finally, cHCC-CCA defines a distinct entity from HCC or iCCA with its specific clinical, biological, pathological and molecular features. Regarding its poor prognosis, there is a need to develop specific therapeutic strategies. cHCC-CCA morphological diagnosis is still challenging for radiologists and pathologists, especially on biopsy specimen.

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