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Intraductal tubulopapillary neoplasms of the bile ducts: clinicopathologic, immunohistochemical, and molecular analysis of 20 cases.
Mod Pathol 2015; 28(9):1249-64MP

Abstract

Intraductal tubulopapillary neoplasm is a well-established entity in the pancreas. A similar, if not identical, tumor occurs also in the biliary tract. We conducted a multicenter study of 20 such lesions, focusing on their clinicopathologic characteristics and molecular profile. Biliary intraductal tubulopapillary neoplasms were seen in patients in their 60s (mean 62 years). The tumors were intrahepatic 70%, extrahepatic 10%, and perihilar 20%; mean tumor size was 6.9 cm. Histologically, all intraductal tubulopapillary neoplasms showed, in addition to their typical tubular pattern, solid areas (70%) or abortive papillae (50%). Necrosis was common (85%), predominantly focal (40%), and with 'comedocarcinoma-like pattern' in 40%. Immunohistochemically, these neoplasms were characterized by the expression of MUC1 (80%) and MUC6 (30%) and by the absence of MUC2 and MUC5AC. Associated invasive carcinomas were present in 16 (80%), mainly conventional tubular adenocarcinoma (50%). The molecular alterations observed included CDKN2A/p16 (intraductal components 44%, invasive 33%) and TP53 (intraductal components 17%, invasive 9%). Mutations in KRAS (intraductal 6%, invasive 0%), PIK3CA (intraductal 6%, invasive 0%), and loss of SMAD4/DPC4 (intraductal 7%, invasive 0%) were rare. No alterations/mutations were identified in IDH1/2, BRAF, GNAS, EGFR, HER2, and β-catenin. Follow-up information was available for 17 patients (85%) with mean follow-up 44 months. Overall combined survival rates showed favorable prognosis: 1 year 100%, 3 years 90%, and 5 years 90%. In conclusion, despite the relatively high incidence of invasive carcinoma (80%), available follow-up suggests that biliary intraductal tubulopapillary neoplasms have an indolent behavior. Molecular analyses highlight the low prevalence of alterations of common oncogenic signaling pathways in intraductal tubulopapillary neoplasm. Further studies using whole-exome sequencing are required to discover yet unknown molecular changes and to understand the carcinogenesis of intraductal tubulopapillary neoplasms.

Authors+Show Affiliations

Institute of Pathology, Technische Universität München, München, Germany.Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.Institute of Pathology, Technische Universität München, München, Germany.Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.Department of Pathology, Ulsan University Hospital, University of Ulsan, College of Medicine, Seoul, Korea.Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.Department of Pathology, University Medical Center, Utrecht, The Netherlands.Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.Department of Diagnostic Pathology, Kobe University, Kobe, Japan.Institute of Pathology, Technische Universität München, München, Germany.Department of Surgery, Technische Universität München, München, Germany.Institute of Pathology, Technische Universität München, München, Germany.Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.Institute of Pathology, Medical University of Innsbruck, Innsbruck, Austria.Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26111977

Citation

Schlitter, Anna Melissa, et al. "Intraductal Tubulopapillary Neoplasms of the Bile Ducts: Clinicopathologic, Immunohistochemical, and Molecular Analysis of 20 Cases." Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, vol. 28, no. 9, 2015, pp. 1249-64.
Schlitter AM, Jang KT, Klöppel G, et al. Intraductal tubulopapillary neoplasms of the bile ducts: clinicopathologic, immunohistochemical, and molecular analysis of 20 cases. Mod Pathol. 2015;28(9):1249-64.
Schlitter, A. M., Jang, K. T., Klöppel, G., Saka, B., Hong, S. M., Choi, H., ... Adsay, V. (2015). Intraductal tubulopapillary neoplasms of the bile ducts: clinicopathologic, immunohistochemical, and molecular analysis of 20 cases. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 28(9), pp. 1249-64. doi:10.1038/modpathol.2015.61.
Schlitter AM, et al. Intraductal Tubulopapillary Neoplasms of the Bile Ducts: Clinicopathologic, Immunohistochemical, and Molecular Analysis of 20 Cases. Mod Pathol. 2015;28(9):1249-64. PubMed PMID: 26111977.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intraductal tubulopapillary neoplasms of the bile ducts: clinicopathologic, immunohistochemical, and molecular analysis of 20 cases. AU - Schlitter,Anna Melissa, AU - Jang,Kee-Taek, AU - Klöppel,Günter, AU - Saka,Burcu, AU - Hong,Seung-Mo, AU - Choi,Hyejeong, AU - Offerhaus,George Johan, AU - Hruban,Ralph H, AU - Zen,Yoh, AU - Konukiewitz,Björn, AU - Regel,Ivonne, AU - Allgäuer,Michael, AU - Balci,Serdar, AU - Basturk,Olca, AU - Reid,Michelle D, AU - Esposito,Irene, AU - Adsay,Volkan, Y1 - 2015/06/26/ PY - 2015/02/01/received PY - 2015/04/28/revised PY - 2015/04/29/accepted PY - 2015/6/27/entrez PY - 2015/6/27/pubmed PY - 2016/6/16/medline SP - 1249 EP - 64 JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JO - Mod. Pathol. VL - 28 IS - 9 N2 - Intraductal tubulopapillary neoplasm is a well-established entity in the pancreas. A similar, if not identical, tumor occurs also in the biliary tract. We conducted a multicenter study of 20 such lesions, focusing on their clinicopathologic characteristics and molecular profile. Biliary intraductal tubulopapillary neoplasms were seen in patients in their 60s (mean 62 years). The tumors were intrahepatic 70%, extrahepatic 10%, and perihilar 20%; mean tumor size was 6.9 cm. Histologically, all intraductal tubulopapillary neoplasms showed, in addition to their typical tubular pattern, solid areas (70%) or abortive papillae (50%). Necrosis was common (85%), predominantly focal (40%), and with 'comedocarcinoma-like pattern' in 40%. Immunohistochemically, these neoplasms were characterized by the expression of MUC1 (80%) and MUC6 (30%) and by the absence of MUC2 and MUC5AC. Associated invasive carcinomas were present in 16 (80%), mainly conventional tubular adenocarcinoma (50%). The molecular alterations observed included CDKN2A/p16 (intraductal components 44%, invasive 33%) and TP53 (intraductal components 17%, invasive 9%). Mutations in KRAS (intraductal 6%, invasive 0%), PIK3CA (intraductal 6%, invasive 0%), and loss of SMAD4/DPC4 (intraductal 7%, invasive 0%) were rare. No alterations/mutations were identified in IDH1/2, BRAF, GNAS, EGFR, HER2, and β-catenin. Follow-up information was available for 17 patients (85%) with mean follow-up 44 months. Overall combined survival rates showed favorable prognosis: 1 year 100%, 3 years 90%, and 5 years 90%. In conclusion, despite the relatively high incidence of invasive carcinoma (80%), available follow-up suggests that biliary intraductal tubulopapillary neoplasms have an indolent behavior. Molecular analyses highlight the low prevalence of alterations of common oncogenic signaling pathways in intraductal tubulopapillary neoplasm. Further studies using whole-exome sequencing are required to discover yet unknown molecular changes and to understand the carcinogenesis of intraductal tubulopapillary neoplasms. SN - 1530-0285 UR - https://www.unboundmedicine.com/medline/citation/26111977/Intraductal_tubulopapillary_neoplasms_of_the_bile_ducts:_clinicopathologic_immunohistochemical_and_molecular_analysis_of_20_cases_ L2 - http://dx.doi.org/10.1038/modpathol.2015.61 DB - PRIME DP - Unbound Medicine ER -