Jonathan P Rivera, Yi-Chen Yeh, Paul Chih-Hsueh Chen, Jen-Fan Hang
{"title":"分子驱动因素不一致的多灶性甲状腺乳头状癌:强调形态学和碰撞肿瘤。","authors":"Jonathan P Rivera, Yi-Chen Yeh, Paul Chih-Hsueh Chen, Jen-Fan Hang","doi":"10.1097/PAS.0000000000002256","DOIUrl":null,"url":null,"abstract":"<p><p>Multifocal papillary thyroid carcinomas (PTCs) are common and the majority of the tumors harbor mutual BRAF p.V600E mutation. This study aimed to investigate a contemporary series of multifocal PTCs with discordant molecular drivers. Consecutive thyroidectomies diagnosed with multifocal PTCs ≥0.5 cm between 2019 and 2023 were reviewed. Immunohistochemistry (IHC) for BRAF VE1 was performed for all tumors. Cases with discordant BRAF IHC results or morphologic discrepancy were identified, and BRAF IHC-negative tumors were subjected to RAS Q61R IHC and/or targeted RNA next-generation sequencing. A total of 770 patients with a main PTC ≥0.5 cm were identified; 255 (33.1%) had multifocal disease, and 142 (18.4%) had at least another PTC ≥0.5 cm. Among them, 13 cases (9.2%, 13/142) had discordant molecular drivers. Twelve cases had one or more BRAF -positive PTCs accompanied by a BRAF -negative PTC (3 with CCDC6::RET fusion, 1 with NCOA4::RET fusion, 1 with ACBD5::RET fusion, 2 with ETV6::NTRK3 fusion, 1 with TG::FGFR1 fusion, 1 with LMTK2::BRAF fusion, 1 with AGK::BRAF fusion and RAS p.Q61R mutation, 1 with RAS p.Q61R mutation, and 1 without detectable molecular drivers). The last case had tumors with discordant fusion drivers ( VIM::NTRK3 and TNS1::BRAF ). Most cases showed tumors that were morphologically distinct (92.3%, 12/13) and occurred in the contralateral lobes (76.9%, 10/13). Notably, we identified 4 cases (30.8%) that presented as collision tumors and 6 cases (46.2%) that showed lymph node metastases, including 2 with simultaneous involvement by tumors with discordant molecular drivers, as novel findings. In summary, a subset (9.2%) of multifocal PTCs had discordant molecular drivers and 84.6% of them were a combination of BRAF -positive and kinase gene fusion-associated PTCs, most with distinct morphologies. Almost half of the cases had nodal metastasis and a third of them showed simultaneous involvement by tumors with discordant molecular drivers. The results highlight the clinical importance of identifying such cases, given the potentially different treatments.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1359-1371"},"PeriodicalIF":4.5000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multifocal Papillary Thyroid Carcinomas With Discordant Molecular Drivers: Emphasizing the Morphology and Collision Tumors.\",\"authors\":\"Jonathan P Rivera, Yi-Chen Yeh, Paul Chih-Hsueh Chen, Jen-Fan Hang\",\"doi\":\"10.1097/PAS.0000000000002256\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Multifocal papillary thyroid carcinomas (PTCs) are common and the majority of the tumors harbor mutual BRAF p.V600E mutation. This study aimed to investigate a contemporary series of multifocal PTCs with discordant molecular drivers. Consecutive thyroidectomies diagnosed with multifocal PTCs ≥0.5 cm between 2019 and 2023 were reviewed. Immunohistochemistry (IHC) for BRAF VE1 was performed for all tumors. Cases with discordant BRAF IHC results or morphologic discrepancy were identified, and BRAF IHC-negative tumors were subjected to RAS Q61R IHC and/or targeted RNA next-generation sequencing. A total of 770 patients with a main PTC ≥0.5 cm were identified; 255 (33.1%) had multifocal disease, and 142 (18.4%) had at least another PTC ≥0.5 cm. Among them, 13 cases (9.2%, 13/142) had discordant molecular drivers. Twelve cases had one or more BRAF -positive PTCs accompanied by a BRAF -negative PTC (3 with CCDC6::RET fusion, 1 with NCOA4::RET fusion, 1 with ACBD5::RET fusion, 2 with ETV6::NTRK3 fusion, 1 with TG::FGFR1 fusion, 1 with LMTK2::BRAF fusion, 1 with AGK::BRAF fusion and RAS p.Q61R mutation, 1 with RAS p.Q61R mutation, and 1 without detectable molecular drivers). The last case had tumors with discordant fusion drivers ( VIM::NTRK3 and TNS1::BRAF ). Most cases showed tumors that were morphologically distinct (92.3%, 12/13) and occurred in the contralateral lobes (76.9%, 10/13). Notably, we identified 4 cases (30.8%) that presented as collision tumors and 6 cases (46.2%) that showed lymph node metastases, including 2 with simultaneous involvement by tumors with discordant molecular drivers, as novel findings. In summary, a subset (9.2%) of multifocal PTCs had discordant molecular drivers and 84.6% of them were a combination of BRAF -positive and kinase gene fusion-associated PTCs, most with distinct morphologies. Almost half of the cases had nodal metastasis and a third of them showed simultaneous involvement by tumors with discordant molecular drivers. The results highlight the clinical importance of identifying such cases, given the potentially different treatments.</p>\",\"PeriodicalId\":7772,\"journal\":{\"name\":\"American Journal of Surgical Pathology\",\"volume\":\" \",\"pages\":\"1359-1371\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Surgical Pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/PAS.0000000000002256\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/31 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PATHOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Surgical Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/PAS.0000000000002256","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/31 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
Multifocal Papillary Thyroid Carcinomas With Discordant Molecular Drivers: Emphasizing the Morphology and Collision Tumors.
Multifocal papillary thyroid carcinomas (PTCs) are common and the majority of the tumors harbor mutual BRAF p.V600E mutation. This study aimed to investigate a contemporary series of multifocal PTCs with discordant molecular drivers. Consecutive thyroidectomies diagnosed with multifocal PTCs ≥0.5 cm between 2019 and 2023 were reviewed. Immunohistochemistry (IHC) for BRAF VE1 was performed for all tumors. Cases with discordant BRAF IHC results or morphologic discrepancy were identified, and BRAF IHC-negative tumors were subjected to RAS Q61R IHC and/or targeted RNA next-generation sequencing. A total of 770 patients with a main PTC ≥0.5 cm were identified; 255 (33.1%) had multifocal disease, and 142 (18.4%) had at least another PTC ≥0.5 cm. Among them, 13 cases (9.2%, 13/142) had discordant molecular drivers. Twelve cases had one or more BRAF -positive PTCs accompanied by a BRAF -negative PTC (3 with CCDC6::RET fusion, 1 with NCOA4::RET fusion, 1 with ACBD5::RET fusion, 2 with ETV6::NTRK3 fusion, 1 with TG::FGFR1 fusion, 1 with LMTK2::BRAF fusion, 1 with AGK::BRAF fusion and RAS p.Q61R mutation, 1 with RAS p.Q61R mutation, and 1 without detectable molecular drivers). The last case had tumors with discordant fusion drivers ( VIM::NTRK3 and TNS1::BRAF ). Most cases showed tumors that were morphologically distinct (92.3%, 12/13) and occurred in the contralateral lobes (76.9%, 10/13). Notably, we identified 4 cases (30.8%) that presented as collision tumors and 6 cases (46.2%) that showed lymph node metastases, including 2 with simultaneous involvement by tumors with discordant molecular drivers, as novel findings. In summary, a subset (9.2%) of multifocal PTCs had discordant molecular drivers and 84.6% of them were a combination of BRAF -positive and kinase gene fusion-associated PTCs, most with distinct morphologies. Almost half of the cases had nodal metastasis and a third of them showed simultaneous involvement by tumors with discordant molecular drivers. The results highlight the clinical importance of identifying such cases, given the potentially different treatments.
期刊介绍:
The American Journal of Surgical Pathology has achieved worldwide recognition for its outstanding coverage of the state of the art in human surgical pathology. In each monthly issue, experts present original articles, review articles, detailed case reports, and special features, enhanced by superb illustrations. Coverage encompasses technical methods, diagnostic aids, and frozen-section diagnosis, in addition to detailed pathologic studies of a wide range of disease entities.
Official Journal of The Arthur Purdy Stout Society of Surgical Pathologists and The Gastrointestinal Pathology Society.