Pathogenesis of Cholangiolocellular Carcinoma: Possibility of an Interlobular Duct Origin

Cholangiolocellular carcinoma (CoCC) is categorized as a different entity from ordinary intrahepatic cholangiocarcinoma (ICC) due to its unique clinical, radiological and histological features. The lesion is supposed to originate from cholangioles, where hepatic stem/progenitor cells exist. However, the interlobular duct is also speculated to be the origin of CoCC. According to the findings of morphometric and immunohistochemical studies, CoCC closely resembles the interlobular duct. The unique clinical and pathological features of this disease can also be explained by the interlobular duct origin theory. The malignant counterparts of cholangioles and interlobular ducts have been categorized as CoCC to date. In order to differentiate between true CoCC (cholangiole origin) and pseudo-CoCC (interlobular duct origin), assessing the size of the cancer duct, positivity for c-Kit and coexistence of an ordinary ICC component is useful.