Tao Wang, Gokce Askan, Kerem Ozcan, Satshil Rana, Ahmet Zehir, Umeshkumar K Bhanot, Rhonda K Yantiss, Deepthi S Rao, Samuel J Wahl, Pelin Bagci, Serdar Balci, Vinod Balachandran, William R Jarnagin, N Volkan Adsay, David S Klimstra, Olca Basturk
{"title":"胆管导管内肿瘤包括形态学和遗传学上不同的实体。","authors":"Tao Wang, Gokce Askan, Kerem Ozcan, Satshil Rana, Ahmet Zehir, Umeshkumar K Bhanot, Rhonda K Yantiss, Deepthi S Rao, Samuel J Wahl, Pelin Bagci, Serdar Balci, Vinod Balachandran, William R Jarnagin, N Volkan Adsay, David S Klimstra, Olca Basturk","doi":"10.5858/arpa.2022-0343-OA","DOIUrl":null,"url":null,"abstract":"<p><strong>Context.—: </strong>Tumoral (grossly visible) intraductal neoplasms of the bile ducts are still being characterized.</p><p><strong>Objective.—: </strong>To investigate their morphologic, immunohistochemical, and molecular features.</p><p><strong>Design.—: </strong>Forty-one cases were classified as gastric-, intestinal-, pancreatobiliary-type intraductal papillary neoplasm (IPN), intraductal oncocytic papillary neoplasm (IOPN), or intraductal tubulopapillary neoplasm (ITPN) on the basis of histology. All neoplasms were subjected to targeted next-generation sequencing.</p><p><strong>Results.—: </strong>The mean age at diagnosis was 69 years (42-81 years); male to female ratio was 1.3. Most neoplasms (n = 23, 56%) were extrahepatic/large (mean size, 4.6 cm). The majority (n = 32, 78%) contained high-grade dysplasia, and 68% (n = 28) revealed invasion. All gastric-type IPNs (n = 9) and most ITPNs/IOPNs showed consistent colabeling for CK7/MUC6, which was less common among others (P = .004). Intestinal-type IPNs (n = 5) showed higher rates of CK20 expression than others (P < .001). Overall, the most commonly mutated genes included TP53 and APC, while copy number variants affected ELF3 and CDKN2A/B. All gastric-type IPNs contained an alteration affecting the Wnt signaling pathway; 7 of 9 (78%) showed aberrations in the MAPK pathway. Mutations in APC and KRAS were common in gastric-type IPNs as compared with others (P = .01 for both). SMAD4 was more frequently mutated in intestinal-type IPNs (P = .02). Pancreatobiliary-type IPNs (n = 14) exhibited frequent alterations in tumor suppressor genes including TP53, CDKN2A/B, and ARID2 (P = .04, P = .01 and P = .002, respectively). Of 6 IOPNs analyzed, 3 (50%) revealed ATP1B1-PRKACB fusion. ITPNs (n = 6) showed relatively few recurrent genetic aberrations. Follow-up information was available for 38 patients (median, 58.5 months). The ratio of disease-related deaths was higher for the cases with invasion (56% versus 10%).</p><p><strong>Conclusions.—: </strong>Tumoral intraductal neoplasms of the bile ducts, similar to their counterparts in the pancreas, are morphologically and genetically heterogeneous.</p>","PeriodicalId":8305,"journal":{"name":"Archives of pathology & laboratory medicine","volume":" ","pages":"1390-1401"},"PeriodicalIF":3.7000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Tumoral Intraductal Neoplasms of the Bile Ducts Comprise Morphologically and Genetically Distinct Entities.\",\"authors\":\"Tao Wang, Gokce Askan, Kerem Ozcan, Satshil Rana, Ahmet Zehir, Umeshkumar K Bhanot, Rhonda K Yantiss, Deepthi S Rao, Samuel J Wahl, Pelin Bagci, Serdar Balci, Vinod Balachandran, William R Jarnagin, N Volkan Adsay, David S Klimstra, Olca Basturk\",\"doi\":\"10.5858/arpa.2022-0343-OA\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Context.—: </strong>Tumoral (grossly visible) intraductal neoplasms of the bile ducts are still being characterized.</p><p><strong>Objective.—: </strong>To investigate their morphologic, immunohistochemical, and molecular features.</p><p><strong>Design.—: </strong>Forty-one cases were classified as gastric-, intestinal-, pancreatobiliary-type intraductal papillary neoplasm (IPN), intraductal oncocytic papillary neoplasm (IOPN), or intraductal tubulopapillary neoplasm (ITPN) on the basis of histology. All neoplasms were subjected to targeted next-generation sequencing.</p><p><strong>Results.—: </strong>The mean age at diagnosis was 69 years (42-81 years); male to female ratio was 1.3. Most neoplasms (n = 23, 56%) were extrahepatic/large (mean size, 4.6 cm). The majority (n = 32, 78%) contained high-grade dysplasia, and 68% (n = 28) revealed invasion. All gastric-type IPNs (n = 9) and most ITPNs/IOPNs showed consistent colabeling for CK7/MUC6, which was less common among others (P = .004). Intestinal-type IPNs (n = 5) showed higher rates of CK20 expression than others (P < .001). Overall, the most commonly mutated genes included TP53 and APC, while copy number variants affected ELF3 and CDKN2A/B. All gastric-type IPNs contained an alteration affecting the Wnt signaling pathway; 7 of 9 (78%) showed aberrations in the MAPK pathway. Mutations in APC and KRAS were common in gastric-type IPNs as compared with others (P = .01 for both). SMAD4 was more frequently mutated in intestinal-type IPNs (P = .02). Pancreatobiliary-type IPNs (n = 14) exhibited frequent alterations in tumor suppressor genes including TP53, CDKN2A/B, and ARID2 (P = .04, P = .01 and P = .002, respectively). Of 6 IOPNs analyzed, 3 (50%) revealed ATP1B1-PRKACB fusion. ITPNs (n = 6) showed relatively few recurrent genetic aberrations. Follow-up information was available for 38 patients (median, 58.5 months). The ratio of disease-related deaths was higher for the cases with invasion (56% versus 10%).</p><p><strong>Conclusions.—: </strong>Tumoral intraductal neoplasms of the bile ducts, similar to their counterparts in the pancreas, are morphologically and genetically heterogeneous.</p>\",\"PeriodicalId\":8305,\"journal\":{\"name\":\"Archives of pathology & laboratory medicine\",\"volume\":\" \",\"pages\":\"1390-1401\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2023-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of pathology & laboratory medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.5858/arpa.2022-0343-OA\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICAL LABORATORY TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of pathology & laboratory medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.5858/arpa.2022-0343-OA","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
Tumoral Intraductal Neoplasms of the Bile Ducts Comprise Morphologically and Genetically Distinct Entities.
Context.—: Tumoral (grossly visible) intraductal neoplasms of the bile ducts are still being characterized.
Objective.—: To investigate their morphologic, immunohistochemical, and molecular features.
Design.—: Forty-one cases were classified as gastric-, intestinal-, pancreatobiliary-type intraductal papillary neoplasm (IPN), intraductal oncocytic papillary neoplasm (IOPN), or intraductal tubulopapillary neoplasm (ITPN) on the basis of histology. All neoplasms were subjected to targeted next-generation sequencing.
Results.—: The mean age at diagnosis was 69 years (42-81 years); male to female ratio was 1.3. Most neoplasms (n = 23, 56%) were extrahepatic/large (mean size, 4.6 cm). The majority (n = 32, 78%) contained high-grade dysplasia, and 68% (n = 28) revealed invasion. All gastric-type IPNs (n = 9) and most ITPNs/IOPNs showed consistent colabeling for CK7/MUC6, which was less common among others (P = .004). Intestinal-type IPNs (n = 5) showed higher rates of CK20 expression than others (P < .001). Overall, the most commonly mutated genes included TP53 and APC, while copy number variants affected ELF3 and CDKN2A/B. All gastric-type IPNs contained an alteration affecting the Wnt signaling pathway; 7 of 9 (78%) showed aberrations in the MAPK pathway. Mutations in APC and KRAS were common in gastric-type IPNs as compared with others (P = .01 for both). SMAD4 was more frequently mutated in intestinal-type IPNs (P = .02). Pancreatobiliary-type IPNs (n = 14) exhibited frequent alterations in tumor suppressor genes including TP53, CDKN2A/B, and ARID2 (P = .04, P = .01 and P = .002, respectively). Of 6 IOPNs analyzed, 3 (50%) revealed ATP1B1-PRKACB fusion. ITPNs (n = 6) showed relatively few recurrent genetic aberrations. Follow-up information was available for 38 patients (median, 58.5 months). The ratio of disease-related deaths was higher for the cases with invasion (56% versus 10%).
Conclusions.—: Tumoral intraductal neoplasms of the bile ducts, similar to their counterparts in the pancreas, are morphologically and genetically heterogeneous.
期刊介绍：
Welcome to the website of the Archives of Pathology & Laboratory Medicine (APLM). This monthly, peer-reviewed journal of the College of American Pathologists offers global reach and highest measured readership among pathology journals.
Published since 1926, ARCHIVES was voted in 2009 the only pathology journal among the top 100 most influential journals of the past 100 years by the BioMedical and Life Sciences Division of the Special Libraries Association. Online access to the full-text and PDF files of APLM articles is free.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
