Biliary intraepithelial neoplasia: an international interobserver agreement study and proposal for diagnostic criteria

Abstract

Cholangiocarcinoma of the intrahepatic and extrahepatic bile ducts develops through a multistep histopathologic sequence. Premalignant or non-invasive neoplastic lesions of bile ducts have been historically called biliary dysplasia or atypical biliary epithelium. To this date, no standard terminology or classification system has been offered for these lesions. In 2005, a conceptual framework and diagnostic criteria for biliary intraepithelial neoplasia (BilIN) were proposed using the livers of patients with hepatolithiasis. We report herein an international interobserver agreement study on the diagnosis of biliary non-invasive neoplastic lesions with the goal to obtain a consensus on the terminology and grading. Seventeen pathologists from the United States, Europe and Asia participated in this study. They shared a digital file containing histological pictures of 30 foci of non-invasive neoplastic lesions selected from the biliary system of patients suffering from primary sclerosing cholangitis, choledochal cyst or hepatolithiasis. In the criteria, we proposed in 2005, BilIN was classified into three categories based on the degree of atypia: BilIN-1, BilIN-2 and BilIN-3. In this study, consensus was reached for the terminology of BilIN and the three-grade classification system. Interobserver agreement on the diagnosis was moderate (j-value ¼ 0.45). On the basis of the suggestions and opinions obtained from the 17 participants, the original criteria for BilIN were revised. We now propose a new consensus classification of BilIN that may assist in allowing a more uniform terminology for the diagnosis of biliary noninvasive neoplastic lesions. This classification should help to advance clinical and research applications. Keywords: biliary dysplasia; BilIN; intrahepatic cholangiocarcinoma; cholangiocarcinoma; bile duct Specialties such as gynecology, urology and gastroenterology are facing difficult dilemmas when trying to incorporate 'preneoplastic lesions' into management recommendations that may vary from observa-

Intraductal tubulopapillary neoplasms of the bile ducts: clinicopathologic, immunohistochemical, and molecular analysis of 20 cases

“…10 Intraductal tumors of the extra and/or intra-hepatic bile duct system fulfilling the newly defined diagnostic criteria (see below) were retrieved from the authors' institutional and consultation files and were included in the study. Cases with overt papillary growth or mucinous pyloric gland pattern, small microscopic lesions (not forming tumoral intraepithelial neoplasia), and/or those with MUC5AC expression, e.g., intraductal papillary neoplasms of the bile duct, 9 biliary mucinous cystic neoplasms, 22 biliary intraepithelial neoplasia, 23 as well as intraductal neoplasms of the ampulla were all excluded. 24 …”

Mucinous cystic neoplasms of the liver: a clinicopathological study and comparison with intraductal papillary neoplasms of the bile duct

“…More commonly, biliary intraepithelial neoplasia (biliary dysplasia) evolve into cholangiocarcinoma usually manifesting as an infiltrative tubular adenocarcinoma. 11,21 The other pathway, intraductal papillary neoplasm to invasive cancer, is characterized by a potential progression to both mucinous carcinoma and papillotubular carcinoma, the expression of gastrointestinal markers even in early lesions (adenomas), and a more favourable postoperative prognosis. 11,22 This study suggested that mucinous cystic neoplasm may be a tumour precursor through another route characterized by the least aggressive clinical course and by expression of gastrointestinal molecules during the carcinogenetic process.…”

Intraductal papillary neoplasms of the bile duct: stepwise progression to carcinoma involves common molecular pathways

“…As most tumors are unresectable at the time of diagnosis, early detection at a preinvasive stage is the only hope of cure. Two entities are considered to be precursor lesions of cholangiocarcinoma: biliary intraepithelial neoplasia 1 and intraductal papillary neoplasms. 2 Intraductal papillary neoplasms of the bile duct have been recently included in the World Health Organisation classification of bile duct tumors 3,4 and comprise the previous categories of biliary papilloma and papillomatosis.…”