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。

IF 4.5 1区 医学 Q1 PATHOLOGY American Journal of Surgical Pathology Pub Date : 2024-11-01 Epub Date: 2024-05-31 DOI:10.1097/PAS.0000000000002256
Jonathan P Rivera, Yi-Chen Yeh, Paul Chih-Hsueh Chen, Jen-Fan Hang
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引用次数: 0

摘要

多灶性甲状腺乳头状癌(PTC)很常见,大多数肿瘤都携带BRAF p.V600E基因突变。本研究旨在调查一系列分子驱动因素不一致的多灶性PTC。研究回顾了2019年至2023年期间诊断为多灶PTC≥0.5厘米的连续甲状腺切除术。对所有肿瘤进行了 BRAF VE1 免疫组化(IHC)检查。确定了 BRAF IHC 结果不一致或形态学差异的病例,并对 BRAF IHC 阴性肿瘤进行了 RAS Q61R IHC 和/或靶向 RNA 下一代测序。共发现 770 例主要 PTC ≥0.5 厘米的患者;255 例(33.1%)患有多灶性疾病,142 例(18.4%)至少有另一个 PTC ≥0.5 厘米。其中,13 例(9.2%,13/142)的分子驱动因素不一致。12 例患者有一个或多个 BRAF 阳性 PTC,同时伴有一个 BRAF 阴性 PTC(3 例伴有 CCDC6::RET 融合、1 例伴有 NCOA4::RET 融合、1 例伴有 ACBD5::RET 融合、2 例伴有 ETV6::NTRK3 融合、1 例伴有 TG::FGFR1 融合、1 例伴有 LMTK2::BRAF 融合、1 例伴有 AGK::BRAF 融合和 RAS p. Q61R 突变、1 例伴有 BRAF 阳性 PTC 和 BRAF 阴性 PTC)。Q61R突变,1例有RAS p.Q61R突变,1例未检测到分子驱动因素)。最后一个病例的肿瘤具有不一致的融合驱动因子(VIM::NTRK3 和 TNS1::BRAF)。大多数病例的肿瘤形态独特(92.3%,12/13 例),且发生在对侧肺叶(76.9%,10/13 例)。值得注意的是,我们发现有 4 例(30.8%)表现为碰撞性肿瘤,6 例(46.2%)表现为淋巴结转移,包括 2 例同时受累于分子驱动因素不一致的肿瘤,这些都是新发现。总之,一部分(9.2%)多灶性 PTC 具有不一致的分子驱动因素,其中 84.6% 是 BRAF 阳性和激酶基因融合相关 PTC 的组合,大多数具有不同的形态。近一半的病例有结节转移,其中三分之一的病例同时受累于分子驱动因素不一致的肿瘤。鉴于治疗方法可能不同,这些结果凸显了识别此类病例的临床重要性。
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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.

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来源期刊
CiteScore
10.30
自引率
5.40%
发文量
295
审稿时长
1 months
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.
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