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WHO Classification of Tumours
Biliary intraepithelial neoplasia, grade 3
Gallbladder and extrahepatic biliary tract


Definition

Biliary intraepithelial neoplasia (BilINs) are characterized by atypical epthelial cells with multilayering of nuclei and micropapillary projections into the gallbladder/extrahepatic 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



. These premalignant lesions also occur in intrahepatic bile ducts. The atypical cells have an increased nucleus-to-cytoplasm ratio, partial loss of nuclear polarity, and nuclear hyperchromasia. BilIN-1 and BilIN-2 correspond to low-grade and intermediate-grade lesions and BilIN-3 corresponds to high grade lesions
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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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BilIN of the gallbladder
The incidence of BilIN-3 parallels that of invasive carcinoma and its prevalence is higher in countries in which gallbladder carcinoma is endemic than in countries in which it is sporadic. The incidence of BilIN-3 in gallbladders with lithiasis varies from 0.5% to 3%

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Albores-Saavedra J, Henson DE, and Klimstra DS eds.
Tumors of the Gallbladder, Extrahepatic Bile Ducts, and Ampulla of Vater
Armed Forces Institute of Pathology: Washington, DC 2000



. This variation in the incidence of BilIn-3 is partially attributable to a lack of uniformity in morphological criteria and sampling methods. In addition to cholelithiasis, BilIN-3 occurs in the mucosa adjacent to most invasive carcinomas and can be found in patients with familial adenomatous polyposis (FAP) , sclerosing cholangitis and pancreatobiliary reflux
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Albores-Saavedra J, Henson DE, and Klimstra DS eds.
Tumors of the Gallbladder, Extrahepatic Bile Ducts, and Ampulla of Vater
Armed Forces Institute of Pathology: Washington, DC 2000




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Bergquist A, Glaumann H, Persson B, Broomé U (1998)
Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study.
Hepatology 27: 311-6




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Bergquist A, Glaumann H, Stål P, Wang GS, Broomé U (2001)
Biliary dysplasia, cell proliferation and nuclear DNA-fragmentation in primary sclerosing cholangitis with and without cholangiocarcinoma.
J Intern Med 249: 69-75




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Boberg KM, Jebsen P, Clausen OP, Foss A, Aabakken L, Schrumpf E (2006)
Diagnostic benefit of biliary brush cytology in cholangiocarcinoma in primary sclerosing cholangitis.
J Hepatol 45: 568-74




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Duarte I, Llanos O, Domke H, Harz C, Valdivieso V (1993)
Metaplasia and precursor lesions of gallbladder carcinoma. Frequency, distribution, and probability of detection in routine histologic samples.
Cancer 72: 1878-84




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Gilloteaux J, Combetta J (2005)
Carcinoma in situ of the cystic duct.
Ultrastruct Pathol 29: 79-84




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Haworth AC, Manley PN, Groll A, Pace R (1989)
Bile duct carcinoma and biliary tract dysplasia in chronic ulcerative colitis.
Arch Pathol Lab Med 113: 434-6




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Katabi N, Albores-Saavedra J (2003)
The extrahepatic bile duct lesions in end-stage primary sclerosing cholangitis.
Am J Surg Pathol 27: 349-55




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Lal A, Okonkwo A, Schindler S, De Frias D, Nayar R (2004)
Role of biliary brush cytology in primary sclerosing cholangitis.
Acta Cytol 48: 9-12




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Ludwig J, Wahlstrom HE, Batts KP, Wiesner RH (1992)
Papillary bile duct dysplasia in primary sclerosing cholangitis.
Gastroenterology 102: 2134-8




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Nakanishi Y, Zen Y, Kawakami H, Kubota K, Itoh T, Hirano S, Tanaka E, Nakanuma Y, Kondo S (2008)
Extrahepatic bile duct carcinoma with extensive intraepithelial spread: a clinicopathological study of 21 cases.
Mod Pathol 21: 807-16




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Narayanan Menon KV (2006)
Primary sclerosing cholangitis, chronic ulcerative colitis, and bile duct dysplasia--Case presentation.
Liver Transpl 12: S14




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Suster S, Huszar M, Herczeg E, Bubis JJ (1987)
Adenosquamous carcinoma of the gallbladder with spindle cell features. A light microscopic and immunocytochemical study of a case.
Histopathology 11: 209-14



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BilIN of the extrahepatic bile ducts
BilINs of the extrahepatic and intrahepatic biliary tree share clinical, morphological, and immunophenotypical features

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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