Mucosal dysplasia of the liver and the intraductal variant of peripheral cholangiocarcinoma in hepatolithiasis.

Four cases are reported of the intraductal variant of peripheral cholangiocarcinoma among surgical specimens from 32 cases of hepatolithiasis. The cancers arose from the periphery of the stone-containing bile duct and spread chiefly along the luminal surface. Microscopically, these tumors showed papillary proliferation and therefore were diagnosed as the intraductal spreading type of peripheral cholangiocarcinoma. Mucosal dysplasia also was noticed in the vicinity of the tumors. In six other cases, mucosal dysplasia was observed in the periphery of the stone. Immunohistochemically, anti-CA 19-9 staining was observed diffusely in the cytoplasm of dysplastic lesions and carcinomas. Anti-carcinoembryonic antigen staining was restricted to the luminal surface and/or the supranuclear region of the cytoplasm in carcinomas. It was not identified in dysplastic cells. These results suggest that the mucosal dysplasia occasionally observed near stones is a precursor of the intraductal spreading type of peripheral cholangiocarcinoma in the presence of hepatolithiasis. The authors hypothesize that the lining epithelium of the large bile duct, when persistently exposed to biochemically altered bile, may undergo a carcinomatous transformation through a stage of mucosal dysplasia.