由于存在一种有效的肌动蛋白肽受体激酶（TRK）抑制剂，因此有必要在日常诊断实践中开发出一种有效的策略，以识别富集的甲状腺乳头状癌（PTC）中的NTRK融合人群。大量PTC中NTRK融合的报告患病率约为3％。我们进行了分析，以精确判定携带NTRK融合的PTC的特征组织学特征，并进一步验证全TRK免疫组织化学（IHC）作为筛查工具的诊断效用。在这项研究中，通过pan-TRK IHC筛查了450个已知不含BRAF p.V600E突变的PTC，并通过RNA基于下一代测序（NGS）进行了TRK表达的确认。检测到11个NTRK融合案例（2.4％），所有PTC均属于典型亚型。 NTRK1和NTRK3与9个不同的配对基因融合。大多数案例显示出相似的特征组织学发现。结节性渗透性边界，多结节性生长，以优势滤泡样式为特征，广泛淋巴侵犯，以及突出的结节间和瘤内纤维化是NTRK重排的PTC特征组织学特征。在超声波检查中无法清晰区分与相邻非肿瘤的甲状腺组织，形成不清晰的边缘，在组织学发现中为结节性渗透边界。因此，结节边缘的术前超声波检查结果和最终的组织学发现相一致。在22个经NGS确认的个案中，PTC中的NTRK1/3融合显示出100％（95％C.I.：71.51-100％）的总体敏感性和100％（95％C.I. ：71.51-100％）的特异性。我们的研究提供了NTRK重排PTC术前超声波、组织学、免疫组织化学和分子特征的综合报告。基于这些发现，我们提出了一种分步评估PTC中NTRK融合的算法方法。 ©2023 Elsevier Inc.版权所有。

Due to the availability of a potent tropomyosin-receptor kinase (TRK) inhibitor, it is necessary to develop an effective strategy to identify an enriched population of NTRK fusions in papillary thyroid cancer (PTC) in routine diagnostic practice. The reported prevalence of NTRK fusion in a large cohort of PTC is approximately 3%. We performed an analysis to refine the characteristic histologic features of PTCs harboring NTRK fusions and further validate the diagnostic utility of pan-TRK immunohistochemistry (IHC) as a screening tool. In this study, 450 PTCs known to harbor no BRAF p.V600E mutations were screened by pan-TRK IHC, and the cases with TRK expression were confirmed by RNA-based next-generation sequencing (NGS) assay. Eleven NTRK fusion cases were detected (2.4%) and all PTCs were classic subtypes. NTRK1 and NTRK3 were involved in the fusion with nine different partner genes. Most cases showed similar characteristic histological findings. Nodular permeative border, multinodular growth with a predominantly follicular pattern, extensive lymphatic invasion, and prominent internodular and intratumoral fibrosis were the characteristic histologic features of NTRK-rearranged PTCs. The ill-defined margins in the ultrasonography findings, which could not be clearly distinguished from adjacent non-tumorous thyroid tissue, were nodular permeative margins in histologic findings. Therefore, preoperative ultrasonographic findings in nodule margins were consistent with the final histologic findings. NTRK1/3 fusion in PTCs showed an overall sensitivity of 100% (95% C.I.: 71.51-100%) and specificity of 100% (95% C.I.: 71.51-100%) in the 22 cases examined, as confirmed with NGS. Our study provides an integrative report of the preoperative ultrasonographic, histological, immunohistochemical, and molecular features of NTRK-rearranged PTCs. Based on these findings, we propose an algorithmic approach for the stepwise assessment of NTRK fusions in PTCs.Copyright © 2023. Published by Elsevier Inc.