National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK), Bethesda, MD, United States.
MedStar Clinical Research Center, MedStar Health Research Institute (MHRI), Washington, DC, United States.
Front Endocrinol (Lausanne). 2020 Feb 18;11:53. doi: 10.3389/fendo.2020.00053. eCollection 2020.
Thyroid ultrasound (US), fine needle aspiration biopsy (FNAB), and molecular testing have been widely used to stratify the risk of malignancy in thyroid nodules. The goal of this study was to investigate a novel diagnostic approach for cytologically indeterminate thyroid nodules (ITN) based upon a combination of US features and genetic alterations. We performed a pilot cohort study of patients with ITN (Bethesda III/IV), who underwent surgical treatment. Based on standardized sonographic patterns established by the American Thyroid Association (ATA), each ITN received an US score (X), ranging between 0 and 0.9 according to its risk of thyroid cancer (TC). DNA and RNA were extracted from pathologic material, available for all patients, and subjected to Oncomine™ Comprehensive Assay v2 (OCAv2) next-generation sequencing. Each genetic alteration was annotated based on its strength of association with TC and its sum served as the genomic classifier score (X). The total risk score (TRS) was the sum of X and X. ROC curves were generated to assess the diagnostic accuracy of X, X, and TRS. The study cohort consisted of 50 patients (39 females and 11 males), aged 47.5 ± 14.8 years. Three patients were excluded due to molecular testing failure. Among the remaining 47 patients, 28 (59.6%) were diagnosed with TC. was the most common mutation in papillary TC, fusion was present in NIFTP, pathogenic variants of , and were found in Hürthle cell TC and mutations in medullary TC. The diagnostic accuracy of X and TRS was significantly higher compared with X (88 vs. 62.5%, < 0.001; 85.2 vs. 62.5%, < 0.001, respectively). However, this increased accuracy was due to significantly better sensitivity (80.7 vs. 34.6%, < 0.001; 84.6 vs. 34.6%, < 0.001, respectively) without improved specificity (94.7 vs. 90%, = 0.55; 85.7 vs. 90%, = 0.63, respectively). Molecular testing might not be necessary in ITN with high-risk US pattern (X = 0.9), as specificity of TC diagnosis based on Xus alone is sufficient and not improved with molecular testing. OCAv2 is useful in guiding the management of ITN with low-to-intermediate risk US features (X < 0.9), as it increases the accuracy of TC diagnosis.
甲状腺超声（US）、细针穿刺活检（FNAB）和分子检测已广泛用于对甲状腺结节的恶性风险进行分层。本研究的目的是探讨一种基于 US 特征和遗传改变的新的细胞学不确定甲状腺结节（ITN）诊断方法。我们对接受手术治疗的 ITN（Bethesda III/IV）患者进行了一项试点队列研究。根据美国甲状腺协会（ATA）制定的标准化超声模式，每个 ITN 根据其甲状腺癌（TC）的风险获得一个 US 评分（X），范围为 0 至 0.9。从所有患者的病理标本中提取 DNA 和 RNA，并进行 Oncomine™ Comprehensive Assay v2（OCAv2）下一代测序。根据其与 TC 的关联强度对每个遗传改变进行注释，其总和作为基因组分类器评分（X）。总风险评分（TRS）是 X 和 X 的总和。生成 ROC 曲线以评估 X、X 和 TRS 的诊断准确性。该研究队列包括 50 名患者（39 名女性和 11 名男性），年龄为 47.5±14.8 岁。由于分子检测失败，有 3 名患者被排除在外。在其余 47 名患者中，28 名（59.6%）被诊断为 TC。在乳头状 TC 中最常见的突变是 ，在非典型滤泡性肿瘤（NIFTP）中存在 融合，在 Hurthle 细胞 TC 中发现了致病性变体 ，在髓样 TC 中发现了 突变。与 X（88%对 62.5%， < 0.001；85.2%对 62.5%， < 0.001）相比，X 和 TRS 的诊断准确性显著更高。然而，这种准确性的提高是由于敏感性显著提高（80.7%对 34.6%， < 0.001；84.6%对 34.6%， < 0.001），而特异性没有提高（94.7%对 90%，=0.55；85.7%对 90%，=0.63）。对于高危 US 模式（X = 0.9）的 ITN，分子检测可能不是必需的，因为仅基于 Xus 诊断 TC 的特异性已经足够，并且不会因分子检测而提高。OCAv2 对于低至中度风险 US 特征的 ITN 非常有用（X < 0.9），因为它可以提高 TC 诊断的准确性。
