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

Yoh Zen, N. Volkan Adsay, Krystof Bardadin, Romano Colombari, Linda Ferrell, Hironori Haga, Seung Mo Hong, Prodromos Hytiroglou, Günter Klöppel, Gregory Y. Lauwers, Dirk J. Van Leeuwen, Kenji Notohara, Kiyoko Oshima, Alberto Quaglia, Motoko Sasaki, Fausto Sessa, Arief Suriawinata, Wilson Tsui, Yutaka Atomi, Yasuni Nakanuma

Research output: Contribution to journalArticlepeer-review

242 Scopus citations


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 (κ-value=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 non-invasive neoplastic lesions. This classification should help to advance clinical and research applications.

Original languageEnglish
Pages (from-to)701-709
Number of pages9
JournalModern Pathology
Issue number6
StatePublished - Jun 2007
Externally publishedYes


  • BilIN
  • Bile duct
  • Biliary dysplasia
  • Cholangiocarcinoma
  • Intrahepatic cholangiocarcinoma


Dive into the research topics of 'Biliary intraepithelial neoplasia: An international interobserver agreement study and proposal for diagnostic criteria'. Together they form a unique fingerprint.

Cite this