Tumoral Intraductal Neoplasms of the Bile Ducts Comprise Morphologically and Genetically Distinct Entities.

IF 3.7 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY
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":"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":null,"pages":null},"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}
引用次数: 2

Abstract

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.

胆管导管内肿瘤包括形态学和遗传学上不同的实体。
上下文。胆管内肿瘤(肉眼可见)仍是胆管肿瘤的特征。-:研究其形态学、免疫组织化学和分子特征。-: 41例根据组织学分为胃型、肠型、胰胆型导管内乳头状瘤(IPN)、导管内嗜瘤细胞型乳头状瘤(IOPN)、导管内管状乳头状瘤(ITPN)。所有肿瘤都进行了靶向的下一代测序。-:平均诊断年龄为69岁(42-81岁);男女比例为1.3。大多数肿瘤(n = 23,56 %)为肝外/大(平均大小4.6 cm)。大多数(n = 32, 78%)为高度发育不良,68% (n = 28)为浸润。所有胃型IPNs (n = 9)和大多数ITPNs/IOPNs均表现出CK7/MUC6的一致标贴,而其他类型的CK7/MUC6标贴较少见(P = 0.004)。肠型IPNs (n = 5) CK20表达率高于其他IPNs (P < 0.001)。总体而言,最常见的突变基因包括TP53和APC,而拷贝数变异影响ELF3和CDKN2A/B。所有胃型IPNs均包含影响Wnt信号通路的改变;9例中有7例(78%)出现MAPK通路畸变。APC和KRAS突变在胃型IPNs中较常见(P = 0.01)。SMAD4在肠型IPNs中突变更为频繁(P = 0.02)。胰胆管型ipn (n = 14)表现出肿瘤抑制基因包括TP53、CDKN2A/B和ARID2的频繁改变(P = 0.04、P = 0.01和P = 0.002)。在分析的6个iopn中,3个(50%)显示ATP1B1-PRKACB融合。ITPNs (n = 6)显示相对较少的复发性遗传畸变。38例患者(中位58.5个月)获得随访信息。侵袭病例的疾病相关死亡率更高(56%比10%)。胆管内肿瘤与胰腺的肿瘤相似,在形态和基因上都是异质的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
9.20
自引率
2.20%
发文量
369
审稿时长
3-8 weeks
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信