Extensive biliary intraepithelial neoplasia (BilIN) and multifocal early intrahepatic cholangiocarcinoma in non-biliary cirrhosis

Rougemont-Pidoux, Anne-Laure; Genevay-Infante, Muriel; Mckee, Thomas Alexander; Gremaud, Magali; Mentha, Gilles; Rubbia-Brandt, Laura

doi:10.1007/s00428-010-0899-3

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Title		Extensive biliary intraepithelial neoplasia (BilIN) and multifocal early intrahepatic cholangiocarcinoma in non-biliary cirrhosis
Authors		Rougemont-Pidoux, Anne-Laure Genevay-Infante, Muriel Mckee, Thomas Alexander Gremaud, Magali Mentha, Gilles Rubbia-Brandt, Laura
Published in		Virchows Archiv. 2010, vol. 456, no. 6, p. 711-717
Collection		Open Access - Licence nationale Springer
Abstract		Biliary intraepithelial neoplasia (BilIN), a preneoplastic condition that may precede invasive intrahepatic cholangiocarcinoma (ICC), has been compared to pancreatic intraepithelial neoplasia (PanIN), a precursor lesion of pancreatic carcinoma. Biliary tract carcinoma development and progression is associated with several gene alterations, but BilIN lesions have yet to be studied in detail by molecular techniques. We describe a case of extensive intrahepatic biliary dysplasia, with lesions ranging from BilIN-1 to BilIN-3 lesions, and multifocal microscopic ICC in hepatitis C virus (HCV)- and alcohol-related cirrhosis. The small ICC foci had remained undetected prior to transplantation. Fluorescence in situ hybridization (FISH) analysis was performed on three foci of BilIN-3 lesions and on three microinvasive ICC foci with a combination of three FISH probes directed against genes frequently altered in pancreatic and biliary tract carcinomas. FISH analysis revealed a CDKNA2 heterozygous deletion in one BilIN-3 focus, and in one non-contiguous ICC focus, although the deletion was just above the chosen threshold. No deletions were detected in the genomic regions encoding TP53 and SMAD4. This report documents for the first time the development of multifocal ICC in the setting of extensive biliary dysplasia in a patient with three risk factors, HCV infection, alcohol abuse, and cirrhosis, and suggests heterogeneous carcinogenesis in ICC and possible involvement of the CDKNA2 gene.
Keywords		Adult — Bile Duct Neoplasms/genetics/ pathology — Bile Ducts, Intrahepatic — Cholangiocarcinoma/genetics/ pathology — Genes, p16 — Humans — In Situ Hybridization, Fluorescence — Liver Cirrhosis/ pathology — Male — Precancerous Conditions/genetics/ pathology
Identifiers		DOI: 10.1007/s00428-010-0899-3 PMID: 20428886
Full text		Article (Published version) - Free access Other version: http://www.springerlink.com/content/100455/
Structures		Faculté de médecine / Section de médecine clinique / Département de chirurgie Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research groups		Hépatologie chirurgicale (327) Lymphomes MALT et réplication virale (807) Métastases du foie (657)
Citation (ISO format)		ROUGEMONT-PIDOUX, Anne-Laure et al. Extensive biliary intraepithelial neoplasia (BilIN) and multifocal early intrahepatic cholangiocarcinoma in non-biliary cirrhosis. In: Virchows Archiv, 2010, vol. 456, n° 6, p. 711-717. doi: 10.1007/s00428-010-0899-3 https://archive-ouverte.unige.ch/unige:20704

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Deposited on : 2012-05-23

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Extensive biliary intraepithelial neoplasia (BilIN) and multifocal early intrahepatic cholangiocarcinoma in non-biliary cirrhosis