Well-differentiated cholangiocarcinoma: diagnostic significance of morphologic and immunohistochemical parameters

In order to provide useful criteria for the histologic diagnosis of well-differentiated cholangiocarcinoma, we reviewed 62 cases of this type. We assessed the incidences of various cytological as well as structural atypia, positive staining for carcinoembryonic antigen, secretory component, or carbohydrate antigen 19-9. We also assessed alterations in mucin production in comparison with noncancerous bile duct epithelium (48 cases). Using a computer-assisted multivariate analysis, three indicators--including nuclear size variation, formation of a second gland (distended intracytoplasmic lumina or focal cribriform pattern), and positive reaction in carcinoembryonic antigen--were shown to be the most important histologic parameters for the diagnosis of cholangiocarcinoma. One of the three indicators was occasionally positive in noncancerous bile ducts, but two or three indicators were only found in cholangiocarcinoma (p less than 0.001). The majority of the cases of cholangiocarcinoma were indeed positive for two or three of these criteria (54/62; 87%). Among other atypical changes, irregular nuclear configurations, mitosis, and prominent nucleoli showed a high specificity for cholangiocarcinoma. In addition to the major criteria, combined application of these factors can also be helpful for the actual histologic assessment.