Immunohistochemical study on bile ductular proliferation in various hepatobiliary diseases

Proliferation of the two types of bile ductules, typical and atypical, in the portal and periportal areas was examined in various liver diseases other than cirrhosis to determine any difference in their immunohistochemical properties and presumed histogenesis. While the typical ductules with a well-formed lumen were frequently seen in a large spectrum of diseases, atypical ductules with a poorly defined lumen were encountered much more frequently in prolonged biliary diseases, including primary biliary cirrhosis and primary sclerosing cholangitis, than in nonbiliary hepatic diseases. Immunocytochemically, cytoplasmic keratin was intensively positive in typical ductules, and the degree of its intensity and extent was variable in atypical ductules. Simultaneously, some of the periportal hepatocytes revealed weak staining for keratin. Luminal borders of typical ductules usually revealed an expression of both carcinoembryonic antigen and epithelial membrane antigen, while atypical ductules and periportal hepatocytes lacked epithelial membrane antigen. The atypical ductules, together with the adjoining hepatocytes, appeared on occasion to form anastomosing cords in prolonged biliary diseases. Thus, atypical ductules seem likely to originate from ductular transformation of the periportal hepatocytes and the typical ductules might result from the proliferation of preexisting interlobular bile ducts and ductules.