甲状腺细针穿刺细胞学联合BRAF基因检测的诊断价值

Thyroid cytological examination by using fine needle aspiration biopsy combined with BRAF gene testing: its diagnostic value in differentiating benign from malignant thyroid nodules

目的评价甲状腺细针穿刺细胞学(FNAB)联合BRAF V600E基因检测对甲状腺结节良恶性鉴别的诊断价值。方法总结经手术病理证实的64个甲状腺结节术前超声引导下细针穿刺细胞学检查和BRAF V600E基因检测的资料,以手术后组织病理学结果作为甲状腺结节性质的诊断金标准,分析FNAB、BRAF V600E基因检测以及两者联合诊断的价值。结果 62例患者64个结节(2例双侧)接受手术处理,其中共有44个结节检测到BRAF V600E突变,43个结节术后病理为甲状腺乳头状癌,1个术后病理为结节性甲状腺肿。在44个检测到BRAF V600E突变结节中,FNAB诊断恶性28个,良性6个,无法确定性质10个。在20个未检测到BRAF V600E突变结节中,FNAB诊断恶性5个,良性3,无法确定性质12个,术后病理14个甲状腺乳头状癌,4个结节性甲状腺肿,1个亚急性甲状腺炎,1个甲状腺腺瘤。共57个甲状腺乳头状癌中,检查到BRAF V600E基因突变有43个,突变率为75.4%。与手术病理金标准比较,FNAB判断甲状腺结节良恶性的灵敏度、特异度、阳性预测值、阴性预测值、正确率分别是78.9%、85.7%、97.8%、33.3%、79.7%;BRAF V600E基因检测判断甲状腺结节良恶性的灵敏度、特异度、阳性预测值、阴性预测值、正确率分别是75.4%、85.7%、97.7%、30.0%、76.6%;FNAB联合BRAF V600E基因检测判断甲状腺结节良恶性的灵敏度、特异度、阳性预测值、阴性预测值、正确率分别是94.7%、71.4%、96.4%、62.5%、92.2%。采用Mc Nemar配对资料χ2检验比较FNAB、FNAB联合BRAF基因检测两种诊断方法的差别,P<0.001,两者差异有显著统计学意义。结论对FNAB无法明确性质的甲状腺结节,辅助联合BRAF V600E基因检测,可以提高甲状腺结节良恶性诊断的准确性。

Objective To evaluate the combination use of thyroid fine needle aspiration biopsy （FNAB） and V-Raf murine sarcoma viral oncogene homolog B1 （BRAF） V600E gene mutation testing in differentiating benign from malignant thyroid nodules. Methods A total of 64 patients with pathologically-proved thyroid nodules were included in this study. The clinical data, including preoperative ultrasound-guided thyroid FNAB and BRAF V600E gene mutation detection, were retrospectively analyzed. Taking postoperative histopathological results as diagnostic gold standard for the thyroid nodule, the diagnostic values of simple FNAB, simple BRAF V600E gene mutation testing, and combination use of FNAB and BRAF V600E gene mutation detection were separately assessed. Results In the 62 patients a total of 64 nodules were detected （2 patients having bilateral nodules） and treated with surgery. Of the 64 nodules, BRAF V600E mutation was detected in 44 nodules, and 43 nodules were proved to be thyroid papillary carcinoma by postoperative pathological examination. Among the 44 nodules showing BRAF V600E mutation, FNAB made malignant diagnosis in 28, benign diagnosis in 6, and uncertain diagnosis in 10. Of the 20 nodules showing no BRAF V6OOE mutation, FNAB made malignant diagnosis in 5, benign diagnosis in 3, and uncertain diagnosis in 12. The postoperative pathological examination confirmed that 14 lesions were thyroid papillary carcinoma, 4 lesions were nodular goiter, one lesion was subacute thyroiditis, and one lesion was thyroid adenoma. Among the 57 thyroid papillary carcinomas, BRAF V600E mutation was detected in 43, with the mutation rate being 75.4%. Compared with the gold standard based on pathological diagnosis, the sensitivity, specificity, positive predictive value, negative predictive value, correct diagnosis rate of FNAB for judging benign or malignant thyroid nodules were 78.9%, 85.7%, 97.8%, 33.3% and 79.7% respectively, which of BRAF V600E gene mutation detection for judging benign or malignant thyroid nodules were 75.4%, 85.7%, 97.7%, 30.0% and 76.6% respectively, and which of FNAB plus BRAF V600E gene mutation detection for judging benign or malignant thyroid nodules were 94.7%, 71.4%, 96.4%, 62.5% and 92.2% respectively. By using McNemar paired data χ^2 test to compare FNAB with combination use of FNAB plus BRAF V600E gene mutation detection in diagnosing thyroid nodules, the results indicated that statistically significant deference in differentiating benign from malignant thyroid nodules existed between the two methods （P〈0.001）. Conclusion For the qualitative diagnosis of thyroid nodules which nature cannot be determined by simple FNAB, FNAB combined with BRAF V600E gene mutation detection can improve the diagnostic accuracy for benign and malignant thyroid nodules.