Pancreatic lipase is a useful phenotypic marker of intrahepatic large and septal bile ducts, peribiliary glands, and their malignant counterparts.

Expression of pancreatic lipase in normal, proliferating, and carcinomatous epithelia of the intrahepatic biliary tree was examined by immunohistochemistry in 82 normal livers, 35 hepatolithiatic livers, 11 cholangiocarcinomas (CCs) associated with hepatolithiasis, 34 CCs, and four combined hepatocellular-cholangiocellular carcinomas. The intrahepatic biliary tree was anatomically divided into large ducts, septal ducts, interlobular ducts, bile ductules, and peribiliary glands. In hepatolithiasis, large ducts, septal ducts, and peribiliary glands showed marked proliferation and dysplasia. In normal livers and hepatolithiasis, expression of pancreatic lipase was found in large ducts in 91% and 94%, in septal ducts in 95% and 94%, and in peribiliary glands in 93% and 94%, respectively. Interlobular ducts, bile ductules, and hepatocytes were negative for pancreatic lipase. The immunoreactivity of pancreatic lipase was coarse granular, and was regularly present in the supranuclear and to a lesser degree paranuclear cytoplasm of the epithelial cells. All cases of CCs with hepatolithiasis, which arised from large ducts, expressed pancreatic lipase. In CCs, pancreatic lipase was expressed in the perinuclear cytoplasm of cancer cells in 67% in the hilar type and in 24% in the peripheral type (P < 0.02). The combined hepatocellular-cholangiocellular carcinomas failed to express pancreatic lipase in both elements. These data suggest that large ducts, septal ducts, and peribiliary glands contain pancreatic lipase in normal and proliferative conditions, and that CCs probably arising from these ductal elements continue to express pancreatic lipase. Thus, pancreatic lipase could be a phenotypic marker of large ducts, septal ducts and peribiliary glands as well as their malignant counterparts.