Gondaliya Hetashvi, Aggarwal Suruchi, Khadilkar Kranti, Kumbenahalli Shivaprasad S, Sooragonda Basavaraj, Shetty Anirudh J, Pillai Vijay, Bhushan Vidhya, Shetty Vivek, Dokhe Yogesh, Lakshmikantha Akhila, Kannan Subramanian
Department of Endocrinology and Metabolism, Narayana Health, Bengaluru, Karnataka, India.
Department of Scientific Affairs, Oncology, Medgenome, Bengaluru, Karnataka, India.
Indian J Endocrinol Metab. 2025 Mar-Apr;29(2):178-183. doi: 10.4103/ijem.ijem_313_24. Epub 2025 Apr 29.
The molecular testing of indeterminate thyroid nodules (ITNs) empowers clinicians to make informed treatment decisions. Despite being recommended by the ATA 2015 guidelines, the utility of molecular testing in India is hindered by challenges related to availability and cost-effectiveness, thereby limiting its widespread adoption. We aimed to evaluate the clinical utility of next-generation sequencing (NGS)-based molecular testing in Indian patients with ITNs.
The study included patients with Bethesda III and IV and selected Bethesda II nodules who underwent Thyrotrack NGS-based assay on fine needle aspirate (FNA) material. Surgery was recommended for patients with clinically significant mutations, while others were followed sonographically. Post-surgical histopathology results were compared with mutation variants to calculate the sensitivity, specificity, and negative predictive value of the NGS assay.
Among 35 patients (mean age 37.7 ± 12.4 years, 80% female), 20 (57%) had clinically significant mutations. Surgery was performed on 11 patients. The most common mutation was RAS (detected in 15 patients), followed by BRAF, TSH-R, ETV6/NTRK3, and PAX8/PPARG. Post-surgical outcomes showed an overall sensitivity of 86% and a specificity of 74%, with a negative predictive value of 94%. Among the mutation-negative group, only one patient had a malignancy, and the rest were benign showing a high negative predictive value of the NGS-based testing.
NGS-based assays provide a reliable and cost-effective option for ruling out malignancy in ITNs in India, offering a high negative predictive value and complementing ACR-TIRADS and Bethesda cytology classifications.
对甲状腺结节性质不确定（ITN）进行分子检测，有助于临床医生做出明智的治疗决策。尽管美国甲状腺协会（ATA）2015年指南推荐了分子检测，但在印度，分子检测的应用因可用性和成本效益相关的挑战而受到阻碍，从而限制了其广泛采用。我们旨在评估基于下一代测序（NGS）的分子检测在印度ITN患者中的临床应用价值。
本研究纳入了贝塞斯达III类和IV类以及部分选定的贝塞斯达II类结节患者，这些患者对细针穿刺抽吸（FNA）材料进行了基于Thyrotrack NGS的检测。对于具有临床意义突变的患者，建议进行手术，其他患者则进行超声随访。将手术后的组织病理学结果与突变变体进行比较，以计算NGS检测的敏感性、特异性和阴性预测值。
在35例患者（平均年龄37.7±12.4岁，80%为女性）中，20例（57%）有临床意义的突变。11例患者接受了手术。最常见的突变是RAS（15例患者中检测到），其次是BRAF、TSH-R、ETV6/NTRK3和PAX8/PPARG。手术后的结果显示，总体敏感性为86%，特异性为74%，阴性预测值为94%。在突变阴性组中，只有1例患者为恶性肿瘤，其余为良性，表明基于NGS的检测具有较高的阴性预测值。
基于NGS的检测为排除印度ITN中的恶性肿瘤提供了一种可靠且具有成本效益的选择，具有较高的阴性预测值，可补充美国放射学会（ACR）-甲状腺影像报告和数据系统（TIRADS）及贝塞斯达细胞学分类。
