Yang Zhongbo, Ijaz Komal, Esebua Magda
Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, Missouri, USA.
Diagn Cytopathol. 2025 Jul;53(7):351-356. doi: 10.1002/dc.25474. Epub 2025 Apr 6.
Up to 30% of thyroid nodules, by fine needle aspiration (FNA), have indeterminate cytology, including Bethesda III (atypia of undetermined significance [AUS]), IV (follicular neoplasm/suspicious for follicular neoplasm [FN/SFN]), and V (suspicious for malignancy). Molecular testing is utilized for further risk stratification of these indeterminate thyroid nodules. A multiplatform test (MPTX), one of the commercially offered molecular tests, combines next-generation sequencing panel (ThyGeNEXT) with microRNA expression classifier (ThyraMIR) to help with risk stratification. This study aimed to evaluate the performance of MPTX in cytologically indeterminate thyroid nodules in real-world experience.
All cases with indeterminate thyroid FNA results and corresponding MPTX test results in a period of 5 years were searched and retrieved. Subsequent clinical or surgical follow-up information was obtained. Molecular test results were compared to the histologic diagnoses. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated accordingly.
A total of 106 cases were identified in the search, including 89 Bethesda III and 17 Bethesda IV. Overall MPTX results were negative in 59 cases, positive in 36 cases, and nondiagnostic in 11 cases. Only 17% of cases with negative molecular results had surgery, whereas 86% of those with positive molecular results had surgical follow-up. The false negative rate and false positive rate based on cytologic-histologic correlation (CHC) alone were 70% and 29%, respectively. In addition, based on both surgical and clinical follow-up data, the MPTX tests had an overall sensitivity of 76%, specificity of 75%, NPV of 83%, and PPV of 67%.
This study showed that more than half (56%) of the thyroid nodules with indeterminate cytology had benign molecular results by MPTX testing. The MPTX test showed moderate to high NPV and moderate PPV, suggesting that the MPTX test can be useful as an ancillary study to further risk-stratify cytologically indeterminate thyroid nodules. It is critical, however, to know the limitations of this assay, and the molecular results should be considered in correlation with clinical and radiologic findings.
通过细针穿刺活检（FNA），高达30%的甲状腺结节具有不确定的细胞学结果，包括贝塞斯达Ⅲ类（意义不明确的非典型病变[AUS]）、Ⅳ类（滤泡性肿瘤/可疑滤泡性肿瘤[FN/SFN]）和Ⅴ类（可疑恶性）。分子检测用于对这些不确定的甲状腺结节进行进一步的风险分层。多平台检测（MPTX）是一种商业化的分子检测方法，它将下一代测序panel（ThyGeNEXT）与微小RNA表达分类器（ThyraMIR）相结合，以帮助进行风险分层。本研究旨在评估MPTX在实际临床中对细胞学结果不确定的甲状腺结节的检测性能。
检索并获取5年内所有甲状腺FNA结果不确定且有相应MPTX检测结果的病例。获得后续的临床或手术随访信息。将分子检测结果与组织学诊断结果进行比较。据此计算敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV）。
检索共确定106例病例，包括89例贝塞斯达Ⅲ类和17例贝塞斯达Ⅳ类。总体MPTX结果中，59例为阴性，36例为阳性，11例为无法诊断。分子结果为阴性的病例中只有17%进行了手术，而分子结果为阳性的病例中有86%进行了手术随访。仅基于细胞学-组织学相关性（CHC）的假阴性率和假阳性率分别为70%和29%。此外，基于手术和临床随访数据，MPTX检测的总体敏感性为76%，特异性为75%，NPV为83%，PPV为67%。
本研究表明，超过一半（56%）细胞学结果不确定的甲状腺结节通过MPTX检测显示分子结果为良性。MPTX检测显示出中度至高NPV和中度PPV，表明MPTX检测可作为一项辅助检查，用于对细胞学结果不确定的甲状腺结节进行进一步的风险分层。然而，了解该检测方法的局限性很关键，分子结果应结合临床和影像学表现进行综合考虑。
