Abstract：
BACKGROUND: Chromosomal rearrangements involving one of the NTRK genes result in oncogenic driver mutations in thyroid carcinoma (TC) and serve as a target for therapy. We compared the clinicopathologic features of thyroid carcinomas with NTRK fusions vs. thyroid neoplasms with other malignancy associated gene fusions within our institution.
METHODS: Our pathology archives were searched from 2013 to 2023 for thyroid neoplasms with gene fusions, excluding THADA fusions and medullary thyroid carcinomas.
RESULTS: 55 thyroid lesions were identified: 22 with NTRK fusions (NTRK cohort) and 33 with other fusions (non-NTRK cohort). On fine needle aspiration (FNA), 54% of the NTRK cohort were classified as Category V as per Bethesda System for Reporting Thyroid Cytology (TBSRTC) and 51.5% of non-NTRK cohort as TBSRTC Category III. In the NTRK cohort, the most common reported fusion was ETV6::NTRK3 and the most common reported fusion in the non-NTRK cohort was PAX8::PPAR-gamma. On histologic examination both cohorts were most commonly diagnosed as PTC follicular variant. Invasive features were more common in the NTRK cohort in comparison to the non-NTRK cohort. Locoregional recurrence occurred in 2/22 NTRK cases and 2/33 non-NTRK cases, with average time from surgery to recurrence being 5.5 months and 21 months, respectively. The majority of patients in both groups are alive with no evidence of disease.
CONCLUSIONS: Thyroid neoplasms with a malignancy associated gene fusion are likely to be diagnosed as subtype/variant of PTC. Patients whose thyroid lesions harbor NTRK fusions present with a PTC-FV that on presentation has more aggressive clinicopathologic findings and are likely to have earlier disease recurrence.
METHODS: Our pathology archives were searched from 2013 to 2023 for thyroid neoplasms with gene fusions, excluding THADA fusions and medullary thyroid carcinomas.
RESULTS: 55 thyroid lesions were identified: 22 with NTRK fusions (NTRK cohort) and 33 with other fusions (non-NTRK cohort). On fine needle aspiration (FNA), 54% of the NTRK cohort were classified as Category V as per Bethesda System for Reporting Thyroid Cytology (TBSRTC) and 51.5% of non-NTRK cohort as TBSRTC Category III. In the NTRK cohort, the most common reported fusion was ETV6::NTRK3 and the most common reported fusion in the non-NTRK cohort was PAX8::PPAR-gamma. On histologic examination both cohorts were most commonly diagnosed as PTC follicular variant. Invasive features were more common in the NTRK cohort in comparison to the non-NTRK cohort. Locoregional recurrence occurred in 2/22 NTRK cases and 2/33 non-NTRK cases, with average time from surgery to recurrence being 5.5 months and 21 months, respectively. The majority of patients in both groups are alive with no evidence of disease.
CONCLUSIONS: Thyroid neoplasms with a malignancy associated gene fusion are likely to be diagnosed as subtype/variant of PTC. Patients whose thyroid lesions harbor NTRK fusions present with a PTC-FV that on presentation has more aggressive clinicopathologic findings and are likely to have earlier disease recurrence.
摘要：
背景：涉及NTRK基因之一的染色体重排导致甲状腺癌（TC）的致癌驱动突变，并作为治疗的靶标。我们比较了NTRK融合与甲状腺癌的临床病理特征。甲状腺肿瘤与我们机构内其他恶性肿瘤相关基因融合。
方法：我们在2013-2023年的病理档案中检索了具有基因融合的甲状腺肿瘤，不包括THADA融合和甲状腺髓样癌。
结果：共发现55个甲状腺病变：22个为NTRK融合（NTRK队列），33个为其他融合（非NTRK队列）。细针抽吸(FNA)根据Bethesda甲状腺细胞学报告系统（TBSRTC），NTRK队列的54％被归类为V类，非NTRK队列的51.5％被归类为TBSRTCIII类。在NTRK队列中，在非NTRK队列中,最常见的融合是ETV6::NTRK3,最常见的融合是PAX8::PPAR-γ.在组织学检查中，两个队列最常诊断为PTC卵泡变异。与非NTRK队列相比，NTRK队列中的侵入性特征更常见。局部复发发生在2/22NTRK病例和2/33非NTRK病例中，从手术到复发的平均时间为5.5个月和21个月，分别。两组中的大多数患者都活着，没有疾病的证据。
结论：具有恶性相关基因融合的甲状腺肿瘤可能被诊断为PTC的亚型/变异。甲状腺病变携带NTRK融合并伴有PTC-FV的患者在出现时具有更积极的临床病理发现，并且可能具有更早的疾病复发。
方法：我们在2013-2023年的病理档案中检索了具有基因融合的甲状腺肿瘤，不包括THADA融合和甲状腺髓样癌。
结果：共发现55个甲状腺病变：22个为NTRK融合（NTRK队列），33个为其他融合（非NTRK队列）。细针抽吸(FNA)根据Bethesda甲状腺细胞学报告系统（TBSRTC），NTRK队列的54％被归类为V类，非NTRK队列的51.5％被归类为TBSRTCIII类。在NTRK队列中，在非NTRK队列中,最常见的融合是ETV6::NTRK3,最常见的融合是PAX8::PPAR-γ.在组织学检查中，两个队列最常诊断为PTC卵泡变异。与非NTRK队列相比，NTRK队列中的侵入性特征更常见。局部复发发生在2/22NTRK病例和2/33非NTRK病例中，从手术到复发的平均时间为5.5个月和21个月，分别。两组中的大多数患者都活着，没有疾病的证据。
结论：具有恶性相关基因融合的甲状腺肿瘤可能被诊断为PTC的亚型/变异。甲状腺病变携带NTRK融合并伴有PTC-FV的患者在出现时具有更积极的临床病理发现，并且可能具有更早的疾病复发。
