Cholangiocarcinoma: Epidemiology and risk factors

Cholangiocarcinoma (CCA) is a malignant tumour, arising from biliary epithelium at any portion of the biliary tree, characterized by a bad prognosis and poor response to current therapies. CCA is currently classified as intrahepatic (IH-CCA) or extrahepatic (EH-CCA). The distinction between IH-CCA and EH-CCA has become increasingly important, as the epidemiological features (i.e., incidence and risk factors), the biologic and pathologic characteristics and the clinical course are largely different. New insights into hepatic and biliary tree stem cell niches organization, into cancer cells of origin and cancer stem cell biology are currently under evaluation as the biological bases of the observed heterogeneity of CCA and could explain the differences in epidemiology and risk factors between IH- and EH-CCA. The purpose of this manuscript is to revise recent literature dealing with the descriptive epidemiology, risk factors and clinical-pathological heterogeneity of CCA with a special effort to compare IH- versus EH-CCA.