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WHO Classification of Tumours
Biliary intraepithelial neoplasia, grade 3
Liver and intrahepatic bile ducts


Definition

Biliary intraepithelial neoplasia (BilIN) is a premalignant flat lesion arising from the intrahepatic large bile ducts. BilIN is not infrequently encountered in the intrahepatic large bile ducts in chronic biliary diseases such as hepatolithiasis
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Zen Y, Aishima S, Ajioka Y, Haratake J, Kage M, Kondo F, Nimura Y, Sakamoto M, Sasaki M, Shimamatsu K, Wakasa K, Park YN, Chen MF, Atomi Y, Nakanuma Y (2005)
Proposal of histological criteria for intraepithelial atypical/proliferative biliary epithelial lesions of the bile duct in hepatolithiasis with respect to cholangiocarcinoma: preliminary report based on interobserver agreement.
Pathol Int 55: 180-8



. BilINs are characterized by atypical epithelial cells with multilayering of nuclei and micropapillary projections into the duct lumen
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Zen Y, Adsay NV, Bardadin K, Colombari R, Ferrell L, Haga H, Hong SM, Hytiroglou P, Klöppel G, Lauwers GY, van Leeuwen DJ, Notohara K, Oshima K, Quaglia A, Sasaki M, Sessa F, Suriawinata A, Tsui W, Atomi Y, Nakanuma Y (2007)
Biliary intraepithelial neoplasia: an international interobserver agreement study and proposal for diagnostic criteria.
Mod Pathol 20: 701-9




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Zen Y, Aishima S, Ajioka Y, Haratake J, Kage M, Kondo F, Nimura Y, Sakamoto M, Sasaki M, Shimamatsu K, Wakasa K, Park YN, Chen MF, Atomi Y, Nakanuma Y (2005)
Proposal of histological criteria for intraepithelial atypical/proliferative biliary epithelial lesions of the bile duct in hepatolithiasis with respect to cholangiocarcinoma: preliminary report based on interobserver agreement.
Pathol Int 55: 180-8



. The atypical cells have an increased nucleus-tocytoplasm ratio, partial loss of nuclear polarity, and nuclear hyperchromasia. They are divisible into BilIN-1, BilIN-2 and BilIN- 3 according to degree of atypia: BilIN-1 and BilIN-2 correspond to low- and intermediate- grade lesions (ICD-O code, 8148/0), and BilIN-3 to high-grade lesions (ICD-O code, 8148/2)
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Zen Y, Adsay NV, Bardadin K, Colombari R, Ferrell L, Haga H, Hong SM, Hytiroglou P, Klöppel G, Lauwers GY, van Leeuwen DJ, Notohara K, Oshima K, Quaglia A, Sasaki M, Sessa F, Suriawinata A, Tsui W, Atomi Y, Nakanuma Y (2007)
Biliary intraepithelial neoplasia: an international interobserver agreement study and proposal for diagnostic criteria.
Mod Pathol 20: 701-9



. Some peribiliary glands in chronic hepatobiliary diseases may show BilIN lesions. BilINs are also seen in the hilar and extrahepatic bile ducts. Interestingly, similar intraepithelial biliary lesions are also encountered in the small intrahepatic bile ducts in livers with chronic hepatis C, alcoholic cirrhosis, thorotrast deposition, and PSC, suggesting that they may be precursor and early lesions of ICC arising from small bile ducts and ductules
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Fleming KA, Boberg KM, Glaumann H, Bergquist A, Smith D, Clausen OP (2001)
Biliary dysplasia as a marker of cholangiocarcinoma in primary sclerosing cholangitis.
J Hepatol 34: 360-5




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Torbenson M, Yeh MM, Abraham SC (2007)
Bile duct dysplasia in the setting of chronic hepatitis C and alcohol cirrhosis.
Am J Surg Pathol 31: 1410-3



. Extensive intraductal spread of BilINs along the intrahepatic bile ducts without grossly visible tumour lesions has been reported
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Aishima S, Nishihara Y, Tsujita E, Taguchi K, Soejima Y, Taketomi A, Ikeda Y, Maehara Y, Tsuneyoshi M (2008)
Biliary neoplasia with extensive intraductal spread associated with liver cirrhosis: a hitherto unreported variant of biliary intraepithelial neoplasia.
Hum Pathol 39: 939-47




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Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds.)
WHO Classification of Tumours of the Digestive System.
4th Edition
International Agency for Research on Cancer: Lyon 2010



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Commentary: Preneoplastic lesions of the digestive system