Pathology of cholangiocarcinoma

Cholangiocarcinoma, which is endemic in certain geographic regions, shows a strong association with liver fluke infection and hepatolithiasis, with recurrent inflammation and the high consumption of nitrates, nitrites, dimethylnitrosamines and N-nitropyrolidines as probable mutagenic cofactors. K-ras, p53 and bcl-2 have been implicated in cholangiocarcinogenesis and several immunohistological markers have been studied, although none is a reliable predictor of outcome. Three macroscopic types of cholangiocarcinoma have been characterized and implicated to be of prognostic relevance, but their behaviour might be a function of their anatomical location rather than a biological characteristic. Periductal-infiltrating tumours present at an advanced stage with infiltration of the portal pedicle. They arise closer to the hepatic hilum than mass-forming tumours, which tend to be peripherally located and show portal invasion and intrahepatic recurrence. The intraductal tumour shows the best prognosis, and long-term survival has been reported. Poor prognostic factors include large tumour size, multifocality, lymphovascular, perineural and serosal invasion, lymph node metastases and involvement of resection margins. Survival following surgical resection, the mainstay of treatment, is generally very poor.