The ThyroSeq next-generation sequencing test refines the risk of malignancy in cytologically indeterminate thyroid nodules. Specific genetic alterations have distinct cancer probabilities and clinical phenotypes. There is limited data on the association between specific genetic alterations and histopathologic features. The aim of this study was to evaluate specific ThyroSeq alterations in prognosticating high-risk histopathologic characteristics. We performed a retrospective single-institution study of all patients diagnosed with indeterminate thyroid nodules (May 2016–December 2019) who had a mutation identified with ThyroSeq v2 or v3 and underwent surgical resection. Specific genetic alterations were correlated with surgical histopathology. The main outcomes were risk of malignancy and structural recurrence risk based on histopathologic features and the 2015 American Thyroid Association (ATA) risk stratification. Of the 78 nodules, 50 (64%) were thyroid cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on surgical histopathology. Nodules with high-risk TERT or TP53 combination mutations (TERT/TP53) and those with BRAF-like mutations were associated with a 100% probability of cancer and higher rates of extrathyroidal extension and regional nodal involvement than nodules with RAS-like mutations. Among nodules with RAS-like mutations, there was an even distribution between benign, NIFTP, and malignant results, the latter of which were all ATA low risk for structural disease recurrence. Overall, TERT/TP53 and BRAF-like ThyroSeq mutations are associated with an increased cancer probability and risk of recurrence defined by histopathologic features, while RAS-like mutations are associated with lower cancer probability and indolent disease. Individualized management, including extent of surgery, should be considered based on specific genetic alterations found in cytologically indeterminate thyroid nodules.

ThyroSeq 新一代测序检测可降低细胞学不确定的甲状腺结节的恶性风险。特定的基因改变具有不同的癌症概率和临床表型。关于特定遗传改变与组织病理学特征之间关联的数据有限。本研究的目的是评估特定的 ThyroSeq 改变在预测高风险组织病理学特征方面的作用。我们对所有被诊断患有不确定甲状腺结节（2016 年 5 月至 2019 年 12 月）且具有 ThyroSeq v2 或 v3 突变并接受手术切除的患者进行了一项回顾性单机构研究。特定的基因改变与手术组织病理学相关。主要结果是基于组织病理学特征和 2015 年美国甲状腺协会 (ATA) 风险分层的恶性肿瘤风险和结构性复发风险。在 78 个结节中，50 个 (64%) 是甲状腺癌或具有乳头状核特征的非侵入性甲状腺滤泡性肿瘤 (NIFTP)，手术组织病理学证实。高危结节TERT或TP53组合突变 ( TERT / TP53 ) 和那些具有BRAF样突变的突变与 100% 的癌症概率相关，并且与具有RAS样突变的结节相比，甲状腺外扩展和区域淋巴结受累的发生率更高。在具有RAS样突变的结节中，良性、NIFTP和恶性结果之间分布均匀，后者均为ATA低结构性疾病复发风险。总体而言，TERT / TP53和BRAF类 ThyroSeq 突变与增加的癌症概率和由组织病理学特征定义的复发风险相关，而类RAS突变与较低的癌症概率和惰性疾病相关。个体化管理，包括手术范围，应根据细胞学不确定的甲状腺结节中发现的特定基因改变来考虑。