Combined hepatocellular-cholangiocarcinoma: An update

Area of Science:

• Hepatobiliary pathology
• Tumorigenesis
• Cancer classification

Background:

• Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) presents dual differentiation of hepatocytes and biliary epithelium.
• Classical hepatocellular carcinoma (HCC) risk factors are implicated in cHCC-CCA development.
• The 2019 WHO classification refined cHCC-CCA diagnosis based on morphology and immunohistochemistry.

Purpose of the Study:

• To review the evolving pathological definition and diagnostic challenges of cHCC-CCA.
• To discuss the molecular underpinnings and cell of origin for cHCC-CCA.
• To highlight the clinical implications, prognosis, and therapeutic limitations for cHCC-CCA.

Main Methods:

• Morphological analysis using routine staining.
• Immunohistochemistry for subtype identification.
• Review of molecular evidence and clinical data.

Main Results:

• cHCC-CCA diagnosis relies on morphology, with intermediate cell carcinoma as a subtype.
• "Cholangiolocellular carcinoma" is now classified under intrahepatic cholangiocarcinoma (iCCA).
• Molecular data supports a clonal origin with genetic alterations seen in HCC and/or iCCA.

Conclusions:

• Morphological diagnosis of cHCC-CCA remains challenging, particularly on biopsies.
• The cell of origin for cHCC-CCA is an active area of research.
• cHCC-CCA has a poor prognosis, similar to iCCA, with limited curative options beyond resection.