title: Proliferative index facilitates distinction between benign biliary lesions and intrahepatic cholangiocarcinoma.
abstract: Differentiation between benign and malignant lesions of the hepatic biliary tree may pose a diagnostic problem because well-differentiated intrahepatic cholangiocarcinoma may mimic biliary hamartoma, bile duct adenoma, or parenchymal extinction. We evaluated Ki-67 proliferative index and p53 status by immunohistochemical staining to aid in exclusion of cholangiocarcinoma. Fourteen biliary hamartomas, 21 bile duct adenomas, and 11 livers with parenchymal extinction were compared with 26 intrahepatic cholangiocarcinomas (16 well-differentiated and 10 moderately or poorly differentiated tumors). We found an increased proliferative index in intrahepatic cholangiocarcinomas compared with benign biliary lesions (average 23.0% in cholangiocarcinoma versus 1.4% in all benign biliary lesions, n = 26 versus n = 46, P < .001). No difference in average proliferative index was observed between well-differentiated and moderately/poorly differentiated cholangiocarcinomas (average 22.7% versus 23.3%, n = 16 versus n = 10, P = .92). Average proliferation indices of benign biliary lesions were uniformly low (biliary hamartoma, 1.2%; bile duct adenoma, 2%; parenchymal extinction, 0.5%). Most cholangiocarcinomas (23/26; 88.5%), but none of the benign lesions (0/46; 0%), had proliferative indices greater than 10%. Strong nuclear p53 immunohistochemical staining was only seen in cholangiocarcinomas (9/26; 34.6%) and not in benign biliary lesions (0/46; 0%), although many of the benign lesions showed weak to moderate staining. Immunohistochemical staining for Ki-67 facilitates distinction between benign and malignant lesions of the intrahepatic biliary tree, whereas p53 immunohistochemical staining is less helpful.
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, CA 94143-0102.
authors.forename: Christos G
authors.initials: CG
authors.lastname: Tsokos
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, CA 94143-0102.
authors.forename: Gregor
authors.initials: G
authors.lastname: Krings
authors.affiliation: Department of Pathology, University of Ege Faculty of Medicine, Bornova, 35100, Izmir, Turkey.
authors.forename: Funda
authors.initials: F
authors.lastname: Yilmaz
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, CA 94143-0102.
authors.forename: Linda D
authors.initials: LD
authors.lastname: Ferrell
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, CA 94143-0102. Electronic address: ryan.gill@ucsf.edu.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Gill
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000737:chemistry* / Q000473:pathology; D001660:Biliary Tract Diseases / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000737:chemistry* / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D019394:Ki-67 Antigen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Bile duct adenoma; Biliary hamartoma; Cholangiocarcinoma; Ki-67; Mib1; Von Meyenburg complex