New insights into cholangiocarcinoma: multiple stems and related cell lineages of origin

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that may develop at anylevel of the biliary tree. CCA is currently classified into intrahepatic (iCCA), perihilar (pCCA) anddistal (dCCA) on the basis of its anatomical location. Notably, although these three CCA subtypeshave common features, they also have important inter- and intra-tumor differences that canaffect their pathogenesis and outcome. A unique feature of CCA is that it manifests in the hepaticparenchyma or large intrahepatic and extrahepatic bile ducts, furnished by two distinct stemcell niches: the canals of Hering and the peribiliary glands, respectively. The complexity of CCApathogenesis highlights the need for a multidisciplinary, translational, and systemic approach tothis malignancy. This review focuses on advances in the knowledge of CCA histomorphology, riskfactors, molecular pathogenesis, and subsets of CCA