1 Division of Surgery; University Hospital of Pisa , Pisa, Italy .
2 Division of Pathology, Department of Surgical Pathology; University Hospital of Pisa , Pisa, Italy .
Thyroid. 2016 Mar;26(3):390-4. doi: 10.1089/thy.2015.0311. Epub 2015 Dec 9.
Patients labeled as having indeterminate thyroid nodular disease following fine-needle aspiration cytology are at risk of non-optimal initial surgery: an overly radical total thyroidectomy, or an unnecessary two-stage operation. The objective of this study was to assess the impact of combining mutational markers and ultrasonographic (US) features preoperatively on predicting the risk of malignancy in patients with indeterminate nodules, thereby offering them a tailored initial surgical intervention.
The records of 258 patients who underwent conventional total thyroidectomy for single nodules reported as suspicious for a follicular neoplasm (Bethesda category IV) in a four-year period were reviewed. Main issues addressed included: certain US findings (individually and in combination), mutational markers (BRAF and NRAS), and combinations of both. Correlation of these with malignancy was assessed, as was their ability to predict malignancy. The usefulness of combining the absence of suspicious sonographic features and the absence of mutational markers was also evaluated.
Among the 258 patients with an indeterminate diagnosis, only 90 lesions were found to be malignant. The sonographic features that correlated significantly with malignancy were irregular margins, microcalcifications, and a "taller than wide" shape. The presence of irregular margins was the feature with the highest positive predictive value. Combinations of two or more features were always associated with predictivity in excess of 90%, and at times at 100%. NRAS mutation was the most common gene alteration. Both BRAF and NRAS mutations were mutually exclusive and correlated significantly with malignancy. Their predictivity of malignancy was high, particularly when combined with suspicious sonographic features (100%). The major limitation of both suspicious sonographic features and/or mutational markers was their low occurrence in malignancy. The absence of both mutational markers and suspicious sonographic features proved extremely useful in tailoring surgical strategy, as it could have ultimately spared 143/258 patients (55%) an overly radical thyroidectomy.
The preoperative utility of mutational markers and sonographic features in combination has a synergistic impact. It can predict the risk of malignancy with high accuracy, properly triaging patients to appropriate surgery.
细针穿刺细胞学检查后被标记为不确定的甲状腺结节性疾病的患者存在初始手术不理想的风险：过度激进的甲状腺全切除术，或不必要的两阶段手术。本研究的目的是评估术前结合突变标志物和超声（US）特征对预测不确定结节患者恶性肿瘤风险的影响，从而为他们提供个性化的初始手术干预。
回顾了四年期间 258 例因滤泡性肿瘤可疑（Bethesda 分类 IV）而接受常规甲状腺全切除术的单结节患者的记录。主要解决的问题包括：某些 US 发现（单独和联合）、突变标志物（BRAF 和 NRAS）以及两者的组合。评估了这些与恶性肿瘤的相关性，以及它们预测恶性肿瘤的能力。还评估了结合无可疑超声特征和无突变标志物的组合的有用性。
在 258 例诊断不确定的患者中，仅发现 90 个病变为恶性。与恶性肿瘤显著相关的超声特征是不规则边缘、微钙化和“高大于宽”形状。不规则边缘的存在是具有最高阳性预测值的特征。两个或更多特征的组合始终与预测值超过 90%相关，有时甚至达到 100%。NRAS 突变是最常见的基因改变。BRAF 和 NRAS 突变均相互排斥，与恶性肿瘤显著相关。它们对恶性肿瘤的预测性很高，尤其是与可疑的超声特征结合时（100%）。可疑超声特征和/或突变标志物的主要局限性在于它们在恶性肿瘤中的发生率较低。两者突变标志物和可疑超声特征均不存在的情况下，对制定手术策略极为有用，因为最终可能使 258 例患者中的 143 例（55%）免于过度激进的甲状腺切除术。
术前结合突变标志物和超声特征具有协同作用。它可以以高精度预测恶性肿瘤的风险，适当将患者分诊至适当的手术。
