A variable proportion of
bile duct adenomas of the liver are still confused with metastatic well-differentiated
adenocarcinoma by surgeons and pathologists. We present here three examples of previously undescribed primary hepatic bile duct
tumors that were composed almost entirely of clear cells that closely mimicked metastatic
renal cell carcinoma. They were interpreted as atypical
bile duct adenomas and occurred in two males and one female whose ages ranged from 25 to 64 years. All three
tumors were incidental findings and measured from 0.8 to 1.1 cm. The clear neoplastic cells showed mild nuclear atypia and no mitotic activity. They were arranged in tubules and nests that focally infiltrated the hepatic parenchyma. For comparison, a case of clear cell
cholangiocarcinoma and 13 conventional
bile duct adenomas were examined. The clear cell
cholangiocarcinoma was larger (6.0 cm) and had the tubular pattern of conventional
cholangiocarcinoma and an abundant desmoplastic stroma. The clear cells of this
tumor exhibited greater nuclear atypia and increased mitotic activity. All three atypical
bile duct adenomas expressed
cytokeratin (CK) 7, p53
protein,
epithelial membrane antigen (EMA), and
carcinoembryonic antigen (CEA); they were negative for CK20,
vimentin, Hep Par 1,
chromogranin, and prostatic specific
antigen (PSA) and exhibited less than 10% of Ki-67-positive nuclei. One atypical
bile duct adenoma displayed
luminal immunoreactivity for
villin. With the exception of Ki-67 reactivity, the 13 conventional
bile duct adenomas and the clear cell
cholangiocarcinoma had essentially a similar immunohistochemical profile as that of the atypical clear cell
bile duct adenomas. The absence of an extrahepatic primary
tumor, the histologic features, the immunohistochemical profile, and the fact that all patients are symptom-free 2 months to 18 years after wedge liver biopsy support the interpretation of atypical clear cell
bile duct adenoma. The differential diagnosis with clear cell
hepatocellular carcinoma and metastatic clear cell
carcinomas is discussed.