Abstract
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver malignancy
characterized by the coexistence of both hepatocellular and biliary morphological
differentiation. It is thought to represent less than 5% of all primary liver cancers
and is associated with a dismal clinical course. Due to its rarity and inherent diagnostic
challenges, consensus guidelines for the management of patients with cHCC-CCA are
lacking, and treatments are usually extrapolated from HCC or CCA guidelines. This
review provides an overview of the main clinical and histo-molecular features of cHCC-CCA,
along with its diagnostic and therapeutic challenges. Technological advances have
allowed researchers to progressively elucidate cHCC-CCA's unique biology and heterogeneity.
Several major questions, however, remain, such as the cHCC-CCA cell of origin. Integration
of multi-modal data and use of artificial intelligence provide interesting perspectives
to further improve patient management; however, they will need to be carefully assessed
and validated. A better definition and understanding of this entity will be key to
further planning clinical trials.
Keywords
liver - cancer - cholangiocarcinoma - hepatocellular carcinoma
