New insights into cholangiocarcinoma: multiple stems and related cell lineages of origin
Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that may develop at any
level of the biliary tree. CCA is currently classified into intrahepatic (iCCA), perihilar (pCCA) and
distal (dCCA) on the basis of its anatomical location. Notably, although these three CCA subtypes
have common features, they also have important inter- and intra-tumor differences that can
affect their pathogenesis and outcome. A unique feature of CCA is that it manifests in the hepatic
parenchyma or large intrahepatic and extrahepatic bile ducts, furnished by two distinct stem
cell niches: the canals of Hering and the peribiliary glands, respectively. The complexity of CCA
pathogenesis highlights the need for a multidisciplinary, translational, and systemic approach to
this malignancy. This review focuses on advances in the knowledge of CCA histomorphology, risk
factors, molecular pathogenesis, and subsets of CCA