Chen Hui, Liu Wei, Chen Yan, Jiang Zhengzeng, Ren Yuanyuan, Wu Jiajia, Liu Rui, Zhu Min, Zhang Hongfeng, Ji Yuan
Department of Ultrasonic Diagnosis, The First Hospital of Putian City, Putian 351100, China.
Xiangya Medical Laboratory, Central South University, Changsha 410013, China.
Int J Endocrinol. 2025 Jun 20;2025:7728360. doi: 10.1155/ije/7728360. eCollection 2025.
Fine-needle aspiration (FNA) cytology remains a challenge in the diagnosis of indeterminate thyroid nodules. Molecular testing can bridge the gap left by FNA cytology and improve the diagnostic accuracy of FNA. 786 FNA samples and 40 formalin-fixed paraffin-embedded (FFPE) specimens from thyroid nodules were enrolled in next-generation sequencing (NGS) molecular testing, which included gene mutation and gene fusion analysis. The molecular diagnostic performance was assessed by analyzing sensitivity, specificity, accuracy, negative predictive value (NPV), and positive predictive value (PPV). Among 826 thyroid nodules, 409 were NGS-positive (49.52%), with a high prevalence of V600E (36.32%, 300/826) and (9.32%, 77/826) mutations, a low prevalence of promoter mutations (1.69%, 14/826), and gene fusions involving (1.82%, 15/826), (0.73%, 6/826), (0.24%, 2/826), and (0.12%, 1/826). With the analysis of genetic profiles in thyroid nodules, V600E, mutations, and gene fusions were included in the 6-gene test panel. The overall diagnostic performance of the 6-gene test panel, including sensitivity, specificity, accuracy, NPV, and PPV, was 84.87%, 89.61%, 86.26%, 71.13%, and 95.15%, respectively. For thyroid nodules in Bethesda III, IV, and V, the diagnostic sensitivity, specificity, accuracy, NPV, and PPV of the panel were 85.71%, 88.89%, 86.36%, 61.54%, and 96.77%, respectively. The results reveal that the 6-gene test panel as a "rule in" test in a clinical setting improves the accuracy of FNA cytology, potentially assisting in the diagnosis of the thyroid nodules with indeterminate FNA cytology.
细针穿刺（FNA）细胞学检查在诊断甲状腺结节性质不确定时仍然是一项具有挑战性的任务。分子检测可以弥补FNA细胞学检查留下的空白，提高FNA的诊断准确性。对786份FNA样本和40份来自甲状腺结节的福尔马林固定石蜡包埋（FFPE）标本进行了二代测序（NGS）分子检测，其中包括基因突变和基因融合分析。通过分析敏感性、特异性、准确性、阴性预测值（NPV）和阳性预测值（PPV）来评估分子诊断性能。在826个甲状腺结节中，409个为NGS阳性（49.52%），V600E突变的发生率较高（36.32%，300/826）， 突变的发生率为9.32%（77/826），启动子突变的发生率较低（1.69%，14/826），涉及 、 、 和 的基因融合发生率分别为1.82%（15/826）、0.73%（6/826）、0.24%（2/826）和0.12%（1/826）。通过对甲状腺结节基因谱的分析，V600E、 突变和基因融合被纳入6基因检测panel。该6基因检测panel的总体诊断性能，包括敏感性、特异性、准确性、NPV和PPV，分别为84.87%、89.61%、86.26%、71.13%和95.15%。对于贝塞斯达III、IV和V类的甲状腺结节，该检测panel的诊断敏感性、特异性、准确性、NPV和PPV分别为85.71%、88.89%、86.36%、61.54%和96.77%。结果表明，在临床环境中，6基因检测panel作为一种“纳入”检测方法提高了FNA细胞学检查的准确性，可能有助于诊断FNA细胞学检查结果不确定的甲状腺结节。
