Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
N Engl J Med. 2012 Aug 23;367(8):705-15. doi: 10.1056/NEJMoa1203208. Epub 2012 Jun 25.
Approximately 15 to 30% of thyroid nodules evaluated by means of fine-needle aspiration are not clearly benign or malignant. Patients with cytologically indeterminate nodules are often referred for diagnostic surgery, though most of these nodules prove to be benign. A novel diagnostic test that measures the expression of 167 genes has shown promise in improving preoperative risk assessment.
We performed a 19-month, prospective, multicenter validation study involving 49 clinical sites, 3789 patients, and 4812 fine-needle aspirates from thyroid nodules 1 cm or larger that required evaluation. We obtained 577 cytologically indeterminate aspirates, 413 of which had corresponding histopathological specimens from excised lesions. Results of a central, blinded histopathological review served as the reference standard. After inclusion criteria were met, a gene-expression classifier was used to test 265 indeterminate nodules in this analysis, and its performance was assessed.
Of the 265 indeterminate nodules, 85 were malignant. The gene-expression classifier correctly identified 78 of the 85 nodules as suspicious (92% sensitivity; 95% confidence interval [CI], 84 to 97), with a specificity of 52% (95% CI, 44 to 59). The negative predictive values for "atypia (or follicular lesion) of undetermined clinical significance," "follicular neoplasm or lesion suspicious for follicular neoplasm," or "suspicious cytologic findings" were 95%, 94%, and 85%, respectively. Analysis of 7 aspirates with false negative results revealed that 6 had a paucity of thyroid follicular cells, suggesting insufficient sampling of the nodule.
These data suggest consideration of a more conservative approach for most patients with thyroid nodules that are cytologically indeterminate on fine-needle aspiration and benign according to gene-expression classifier results. (Funded by Veracyte.).
通过细针抽吸评估的甲状腺结节中，约有 15%至 30% 不能明确为良性或恶性。对于细胞学不确定的结节患者，通常会进行诊断性手术，尽管大多数这些结节证实为良性。一种新的诊断测试，测量 167 个基因的表达，已显示出改善术前风险评估的前景。
我们进行了一项为期 19 个月的前瞻性多中心验证研究，涉及 49 个临床站点、3789 名患者和 4812 个 1 厘米或更大的需要评估的甲状腺结节的细针抽吸样本。我们获得了 577 个细胞学不确定的抽吸样本，其中 413 个有相应的切除病变的组织病理学标本。中心、盲法组织病理学复查结果作为参考标准。符合纳入标准后，使用基因表达分类器测试了本分析中的 265 个不确定结节，并评估了其性能。
在 265 个不确定结节中，85 个为恶性。基因表达分类器正确识别了 85 个结节中的 78 个为可疑（92%的敏感性；95%置信区间 [CI]，84 至 97），特异性为 52%（95% CI，44 至 59）。“不确定临床意义的非典型性（或滤泡性病变）”、“滤泡性肿瘤或疑似滤泡性肿瘤的病变”或“可疑细胞学发现”的阴性预测值分别为 95%、94%和 85%。对 7 个假阴性结果的分析显示，6 个样本中甲状腺滤泡细胞稀少，提示结节取样不足。
这些数据表明，对于大多数细胞学不确定的甲状腺结节患者，如果根据基因表达分类器的结果为良性，可考虑采用更保守的方法。（由 Veracyte 资助）。
