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.