Pathological observations of intrahepatic peribiliary glands in 1,000 consecutive autopsy livers. II. A possible source of cholangiocarcinoma.

It remains unclear whether atypical epithelial lesions, including carcinomas and precancerous lesions, develop in intraheptic peribiliary glands. This question was tested in this study. One thousand livers from consecutive autopsies were surveyed and 201 livers with bile duct carcinomas or metastatic malignant neoplasms were excluded because atypical epithelial lesions of the glands were difficult to distinguish from the primary or metastatic malignant cells. Consequently, 799 livers were examined for the atypical epithelial lesions by histological, mucin-histochemical and immunohistochemical methods. The atypical epithelial lesions were divisible into papillary hyperplasia, atypical hyperplasia and carcinomatous transformation. Of the 799 livers, papillary hyperplasia was only found in six livers (0.8%), papillary hyperplasia and atypical hyperplasia coexisted in four livers (0.5%) and carcinomatous transformation and atypical hyperplasia coexisted in one liver (0.1%). Mucin-histochemical study showed that the intracytoplasmic location of mucin was different between carcinomatous transformation and normal peribiliary glands. From an immunohistochemical standpoint, epithelial cells of the atypical epithelial lesions showed stronger immunoreactivities to carcinoembryonic antigen, carbohydrate antigen 19-9 and DU-PAN-2 than those of normal intrahepatic peribiliary glands. These findings suggest that intrahepatic cholangiocarcinomas arising from intrahepatic peribiliary glands actually exist, and that papillary and atypical hyperplasia of the peribiliary glands may precede this type of cholangiocarcinoma.