Thyroid & Endocrine Center of Florida, Sarasota, Florida, USA.
Cedars-Sinai Medical Center, Los Angeles, California, USA.
Diagn Cytopathol. 2020 Dec;48(12):1254-1264. doi: 10.1002/dc.24564. Epub 2020 Aug 7.
Approximately 25% of thyroid nodule fine-needle aspirates (FNAs) have cytology that is indeterminate for malignant disease. Accurate risk stratification of these FNAs with ancillary testing would reduce unnecessary thyroid surgery.
We evaluated the performance of an ancillary multiplatform test (MPTX) that has three diagnostic categories (negative, moderate, and positive). MPTX includes the combination of a mutation panel (ThyGeNEXT®) and a microRNA risk classifier (ThyraMIR®). A blinded, multicenter study was performed using consensus histopathology diagnosis among three pathologists to validate test performance.
Unanimous consensus diagnosis was reached in 197 subjects with indeterminate thyroid nodules; 36% had disease. MPTX had 95% sensitivity (95% CI,86%-99%) and 90% specificity (95% CI,84%-95%) for disease in prevalence adjusted nodules with Bethesda III and IV cytology. Negative MPTX results ruledout disease with 97% negative predictive value (NPV; 95% CI,91%-99%) at a 30% disease prevalence, while positive MPTX results ruledin high risk disease with 75% positive predictive value (PPV; 95% CI,60%-86%). Such results are expected in four out of five Bethesda III and IV nodules tested, including RAS positive nodules in which the microRNA classifier was useful in rulingin disease. 90% of mutation panel false positives were due to analytically verified RAS mutations detected in benign adenomas. Moderate MPTX results had a moderate rate of disease (39%, 95% CI,23%-54%), primarily due to RAS mutations, wherein the possibility of disease could not be excluded.
Our results emphasize that decisions for surgery should not solely be based on RAS or RAS-like mutations. MPTX informs management decisions while accounting for these challenges.
约 25%的甲状腺结节细针抽吸物（FNA）的细胞学检查结果为恶性疾病不确定。通过辅助检测对这些 FNA 进行准确的风险分层将减少不必要的甲状腺手术。
我们评估了一种辅助多平台检测（MPTX）的性能，该检测有三个诊断类别（阴性、中度和阳性）。MPTX 包括突变面板（ThyGeNEXT®）和 microRNA 风险分类器（ThyraMIR®）的组合。一项盲法、多中心研究使用三位病理学家的共识组织病理学诊断来验证检测性能。
在 197 例甲状腺结节不确定的患者中达成了一致的共识诊断；36%的患者有疾病。在贝塞斯达 III 级和 IV 级细胞学的结节中，MPTX 对疾病的敏感性为 95%（95%CI，86%-99%），特异性为 90%（95%CI，84%-95%）。阴性 MPTX 结果排除了 30%疾病患病率时 97%的阴性预测值（NPV；95%CI，91%-99%）的疾病，而阳性 MPTX 结果排除了 75%的高风险疾病（95%CI，60%-86%）。在五个贝塞斯达 III 级和 IV 级结节中，预计有四个会出现这种结果，包括 RAS 阳性结节，其中 microRNA 分类器可用于排除疾病。90%的突变面板假阳性归因于良性腺瘤中检测到的经分析验证的 RAS 突变。中度 MPTX 结果的疾病发生率较高（39%，95%CI，23%-54%），主要是由于 RAS 突变，不能排除疾病的可能性。
我们的研究结果强调，手术决策不应仅基于 RAS 或 RAS 样突变。MPTX 在考虑这些挑战的同时为管理决策提供信息。
