Department of Surgical, Medical, Molecular Pathology and Critical Area, Unit of Pathological Anatomy, University of Pisa, Pisa, Italy.
Cancer Cytopathol. 2014 Oct;122(10):751-9. doi: 10.1002/cncy.21454. Epub 2014 Jun 9.
Fine-needle aspiration (FNA) has been widely accepted as the most crucial step in the preoperative assessment of thyroid nodules, but the false-negative rates are generally reported to be between 3.6% and 10.2%. To lower the overall incidence of this false-negative testing, new reporting systems encourage the molecular testing of thyroid nodules. However, to the authors' knowledge, the role of molecular testing in false-negative FNA has not yet been evaluated.
In total, 1347 consecutive papillary thyroid carcinomas (PTCs) with both cytological and histological diagnoses were collected from the same center. A blinded revision of the false-negative cases was performed. An analysis of the BRAF and Ras genes in the false-negative cases was then performed.
The false-negative rate at the time of primary FNA diagnosis was 4.8% (65 of 1347 cases). False-negative cases were 15 follicular variant PTCs, 2 classical variant, and 1 solid variant that lacked peculiar PTC cytomorphological features. Adequate cellular material for molecular analysis was available only in 54 of the 65 false-negative cases. Mutations were found in 6 cases (11%), and Ras alterations were present in 16 cases (29.6%). The addition of molecular analysis decreased the false-negative rate to 0.4% (5 of 1347 cases).
The results of the current study confirm the feasibility of BRAF and Ras analysis in routine FNA. However, when the false-negative FNA rate is low, the cost-benefit analysis of the detection of BRAF and Ras mutations should be carefully evaluated. Consequently, the authors suggest that preoperative molecular assessment could be helpful for benign nodules, but only in the presence of clinical suspicion of malignancy.
细针穿刺抽吸术（FNA）已被广泛认为是甲状腺结节术前评估中最关键的步骤，但假阴性率一般报告在 3.6%至 10.2%之间。为了降低这种假阴性检测的总体发生率，新的报告系统鼓励对甲状腺结节进行分子检测。然而，据作者所知，分子检测在假阴性 FNA 中的作用尚未得到评估。
总共收集了来自同一中心的 1347 例细胞学和组织学诊断均为甲状腺乳头状癌（PTC）的连续病例。对假阴性病例进行了盲法复查。然后对假阴性病例中的 BRAF 和 Ras 基因进行了分析。
在初次 FNA 诊断时，假阴性率为 4.8%（1347 例中有 65 例）。假阴性病例中包括 15 例滤泡型 PTC、2 例经典型和 1 例实性型，缺乏独特的 PTC 细胞学特征。仅有 54 例假阴性病例有足够的细胞材料进行分子分析。在 6 例（11%）中发现了突变，在 16 例（29.6%）中存在 Ras 改变。添加分子分析将假阴性率降低至 0.4%（1347 例中有 5 例）。
本研究结果证实了 BRAF 和 Ras 分析在常规 FNA 中的可行性。然而，当假阴性 FNA 率较低时，应仔细评估检测 BRAF 和 Ras 突变的成本效益分析。因此，作者建议术前分子评估可能对良性结节有帮助，但仅在存在恶性肿瘤的临床怀疑时。
