Pathogenesis of primary liver carcinomas

Primary liver cancer (PLC) is the third leading cause of cancer death, accounting for 830,180 deaths worldwide in 2020. PLCs are mainly composed of hepatocellular carcinoma (HCC, ∼85%) and intrahepatic cholangiocarcinoma (iCCA, ∼10%).

HCC is PLC characterized by hepatocellular differentiation; in contrast, CCAs are biliary differentiated tumors. HCC and iCCA define a spectrum of PLCs that also include mixed tumors (combined HCC-CCA [cHCC-CCA]), which are much more uncommon (∼1%). They are defined by the presence of HCC and CCA areas in various proportions, as well as, in some cases, the presence of transitional features within the same tumor.