PMID- 20428886 OWN - NLM STAT- MEDLINE DCOM- 20100622 LR - 20211020 IS - 1432-2307 (Electronic) IS - 0945-6317 (Linking) VI - 456 IP - 6 DP - 2010 Jun TI - Extensive biliary intraepithelial neoplasia (BilIN) and multifocal early intrahepatic cholangiocarcinoma in non-biliary cirrhosis. PG - 711-7 LID - 10.1007/s00428-010-0899-3 [doi] AB - 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. FAU - Rougemont, Anne-Laure AU - Rougemont AL AD - Division of Clinical Pathology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1211, Geneva 14, Switzerland. anne-laure.rougemont@hcuge.ch FAU - Genevay, Muriel AU - Genevay M FAU - McKee, Thomas A AU - McKee TA FAU - Gremaud, Magali AU - Gremaud M FAU - Mentha, Gilles AU - Mentha G FAU - Rubbia-Brandt, Laura AU - Rubbia-Brandt L LA - eng PT - Case Reports PT - Journal Article DEP - 20100429 PL - Germany TA - Virchows Arch JT - Virchows Archiv : an international journal of pathology JID - 9423843 SB - IM MH - Adult MH - Bile Duct Neoplasms/genetics/*pathology MH - *Bile Ducts, Intrahepatic MH - Cholangiocarcinoma/genetics/*pathology MH - Genes, p16 MH - Humans MH - In Situ Hybridization, Fluorescence MH - Liver Cirrhosis/*pathology MH - Male MH - Precancerous Conditions/genetics/*pathology EDAT- 2010/04/30 06:00 MHDA- 2010/06/23 06:00 CRDT- 2010/04/30 06:00 PHST- 2009/09/23 00:00 [received] PHST- 2010/02/20 00:00 [accepted] PHST- 2010/01/14 00:00 [revised] PHST- 2010/04/30 06:00 [entrez] PHST- 2010/04/30 06:00 [pubmed] PHST- 2010/06/23 06:00 [medline] AID - 10.1007/s00428-010-0899-3 [doi] PST - ppublish SO - Virchows Arch. 2010 Jun;456(6):711-7. doi: 10.1007/s00428-010-0899-3. Epub 2010 Apr 29.