超声引导下细针穿刺细胞学检查联合BRAFV600E基因突变检测在甲状腺微小结节良恶性鉴别诊断中的价值
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摘要
目的探讨超声引导下细针穿刺细胞学检查联合BRAFV600E基因突变检测在甲状腺微小结节良恶性鉴别诊断中的临床价值。方法选取71例结节最大径线≤10 mm且具有可疑恶性特征的患者,均行超声引导下细针穿刺细胞学检查(FNAB)和BRAFV600E基因突变检测,以手术病理结果作为甲状腺结节性质诊断的金标准,绘制受试者工作特征(ROC)曲线,分析FNAB、BRAFV600E基因突变检测以及两者联合检测对甲状腺微小结节良恶性的鉴别诊断效能。结果 71例甲状腺微小结节的术后病理结果中,恶性的48例均为甲状腺微小乳头状癌(PTMC),良性的23例中,腺瘤5例、桥本甲状腺炎1例、结节性甲状腺肿17例(其中6例局部滤泡上皮异型增生)。与术后病理对照,FNAB术前诊断PTMC的灵敏度77%、特异度91%、诊断符合率82%、ROC曲线下面积(AUC)为0.842。BRAFV600E基因突变检测术前诊断PTMC的灵敏度77%、特异度87%、诊断符合率80%,ROC AUC为0.820。FNAB联合BRAFV600E基因突变术前诊断PTMC的灵敏度90%、特异度78%、诊断符合率85%,ROC AUC为0.860。FNAB联合BRAFV600E基因突变术前检测PTMC的灵敏度高于单独应用FNAB或BRAFV600E基因突变检测(P均<0.05)。结论术前行FNAB联合BRAFV600E基因突变检测能够精确FNAB的诊断,提高术前鉴别诊断甲状腺微小结节良恶性的灵敏度。
Objective To investigate the clinical value of the combined application of ultrasoundguided fine needle aspiration biopsy(FNAB) and BRAFV600 E gene mutation detection in differentiating benign from malignant thyroid nodules smaller than 10 mm. Methods Seventy-one patients with thyroid nodules ≤ 10 mm in diameter with suspected malignant characteristics received FNAB and BRAFV600 E gene mutation detection. Postoperative pathological examination was regarded as the gold standard of clinical diagnosis. The receiver operating characteristic(ROC) curve was delineated. Diagnostic performance of FNAB, BRAFV600 E gene mutation detection and two combined in the differential diagnosis was comparatively analyzed. Results Pathological examination demonstrated that 48 of 71 cases were diagnosed with thyroid papillary carcinoma. Among 23 benign cases, 5 patients were diagnosed with adenomas, 1 with Hashimoto's thyroiditis, and 17 with nodular goiter(including 6 cases of local follicular epithelial dysplasia). Compared with the gold standard based on postoperative pathological examination, the sensitivity, specificity and correct diagnostic rate of preoperative FNAB were 77%, 91% and 82%, respectively. The area under the ROC curve was 0.842. The sensitivity, specificity and correct diagnostic rate of preoperative BRAFV600 E gene mutation detection were 77%, 87% and 80%, respectively. The area under the ROC curve was 0.820. The parameters for FNAB in combination with BRAFV600 E gene mutation detection were 90%, 78% and 85%, respectively. The area under the ROC curve was 0.860. In the diagnosis of papillary thyroid microcarcinoma, the sensitivity of FNAB combined with BRAFV600 E gene mutation detection was significantly higher than that of FNAB or BRAFV600 E gene mutation detection alone(both P < 0.05). Conclusion Preoperative FNAB combined with BRAFV600 E gene mutation detection can improve the diagnostic performance of FNAB and enhance the sensitivity in the diagnosis of thyroid nodules smaller than 10 mm.
Objective To investigate the clinical value of the combined application of ultrasoundguided fine needle aspiration biopsy(FNAB) and BRAFV600 E gene mutation detection in differentiating benign from malignant thyroid nodules smaller than 10 mm. Methods Seventy-one patients with thyroid nodules ≤ 10 mm in diameter with suspected malignant characteristics received FNAB and BRAFV600 E gene mutation detection. Postoperative pathological examination was regarded as the gold standard of clinical diagnosis. The receiver operating characteristic(ROC) curve was delineated. Diagnostic performance of FNAB, BRAFV600 E gene mutation detection and two combined in the differential diagnosis was comparatively analyzed. Results Pathological examination demonstrated that 48 of 71 cases were diagnosed with thyroid papillary carcinoma. Among 23 benign cases, 5 patients were diagnosed with adenomas, 1 with Hashimoto's thyroiditis, and 17 with nodular goiter(including 6 cases of local follicular epithelial dysplasia). Compared with the gold standard based on postoperative pathological examination, the sensitivity, specificity and correct diagnostic rate of preoperative FNAB were 77%, 91% and 82%, respectively. The area under the ROC curve was 0.842. The sensitivity, specificity and correct diagnostic rate of preoperative BRAFV600 E gene mutation detection were 77%, 87% and 80%, respectively. The area under the ROC curve was 0.820. The parameters for FNAB in combination with BRAFV600 E gene mutation detection were 90%, 78% and 85%, respectively. The area under the ROC curve was 0.860. In the diagnosis of papillary thyroid microcarcinoma, the sensitivity of FNAB combined with BRAFV600 E gene mutation detection was significantly higher than that of FNAB or BRAFV600 E gene mutation detection alone(both P < 0.05). Conclusion Preoperative FNAB combined with BRAFV600 E gene mutation detection can improve the diagnostic performance of FNAB and enhance the sensitivity in the diagnosis of thyroid nodules smaller than 10 mm.
引文
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[4]薛金才,刘勤江,田尤新,侯小峰.BRAFV600E及TERT启动子突变在甲状腺微小乳头状癌风险评估中的价值.中国癌症杂志,2018,28(5):335-341.
[5]Tufano RP,Teixeira GV,Bishop J,Carson KA,Xing M.BRAFmutation in papillary thyroid cancer and its value in tailoring initial treatment:a systematicreview and meta-analysis.Medicine(Baltimore),2012,91(5):274-286.
[6]Xing M,Alzahrani AS,Carson KA,Viola D,Elisei R,Bendlova B,Yip L,Mian C,Vianello F,Tuttle RM,Robenshtok E,Fagin JA,Puxeddu E,Fugazzola L,Czarniecka A,Jarzab B,O’Neill CJ,Sywak MS,Lam AK,Riesco-Eizaguirre G,Santisteban P,Nakayama H,Tufano RP,Pai SI,Zeiger MA,Westra WH,Clark DP,Clifton-Bligh R,Sidransky D,Ladenson PW,Sykorova V.Association between BRAF-V600E mutation and mortality in patients with papillary thyroid cancer.JAMA,2013,309(14):1493-501.
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[9]Cibas ES,Ali SZ.The 2017 Bethesda System for reporting thyroid cytopathology.Thyroid,2017,27(11):1341-1346.
[10]Virk RK,Van Dyke AL,Finkelstein A,Prasad A,Gibson J,Hui P,Theoharis CG,Carling T,Roman SA,Sosa JA,Udelsman R,Prasad ML.BRAFV600E mutation in papillary thyroid microcarcinoma:a genotype-phenotype correlation.Mod Pathol,2013,26(1):62-70.
[11]Lesnik D,Cunnane ME,Zurakowski D,Acar GO,Ecevit C,Mace A,Kamani D,Randolph GW.Papillary thyroid carcinoma nodal surgery directed by a preoperative radiographic map utilizing CT scan and ultrasound in all primary and reoperative patients.Head Neck,2014,36(2):191-202.
[12]Zhang LY,Liu ZW,Liu YW,Gao WS,Zheng CJ.Risk factors for nodal metastasis in cN0 papillary thyroid microcarcinoma.Asian Pac J Cancer Prev,2015,16(8):3361-3363.
[13]Elsayed AA,Murdoch C,Murray S,Bashir K.Can thyroid surgery be decided based on ultrasonographic findings,irrespective of cytopathological findings?Five-year retrospective study in a district general hospital.Clin Radiol,2017,72(2):170-174.
[14]李征毅,赵永胜,李锋,刘伟宗,关弘.甲状腺乳头状癌BRAF基因突变与超声及病理特征相关性研究.新医学,2018,49(11):828-833.
[15]刘燕,龚业琼,吴晓莉,申俊玲,李祥.常规超声与B超引导下穿刺细胞学检查在诊断小病灶甲状腺结节中的对比.中国老年学,2017,37(14):3564-3566.
[16]Chiofalo MG,Signoriello S,Fulciniti F,Avenia N,Ristagno S,Lombardi CP,Nicolosi A,Pelizzo MR,Perigli G,Polistena A,Panebianco V,Bellantone R,CalòPG,Boschin IM,Badii B,Di Maio M,Gallo C,Perrone F,Pezzullo L.Predictivity of clinical,laboratory and imaging findings in diagnostic definition of palpable thyroidnodules.A multicenter prospective study.Endocrine,2018,61(1):43-50.
[17]Rosove MH,Peddi PF,Glaspy JA.BRAFV600E inhibition in anaplastic thyroid cancer.N Engl J Med,2013,368(7):684-685.
[18]Xing M,Alzahrani AS,Carson KA,Shong YK,Kim TY,Viola D,Elisei R,BendlováB,Yip L,Mian C,Vianello F,Tuttle RM,Robenshtok E,Fagin JA,Puxeddu E,Fugazzola L,Czarniecka A,Jarzab B,O’Neill CJ,Sywak MS,Lam AK,Riesco-Eizaguirre G,Santisteban P,Nakayama H,Clifton-Bligh R,Tallini G,Holt EH,SykorováV.Association between BRAFV600E mutation and recurrence of papillary thyroid cancer.JClin Oncol,2015,33(1):42-50.--
[2]Li F,Chen G,Sheng C,Gusdon AM,Huang Y,Lv Z,Xu H,Xing M,Qu S.BRAFV600E mutation in papillary thyroid microcarcinoma:a meta-analysis.Endocr Relat Cancer,2015,22(2):159-168.
[3]Godbert Y,Henriques-Figueiredo B,Cazeau AL,Carrat X,Stegen M,Soubeyran I,Bonichon F.A papillary thyroid microcarcinoma revealed by a single bone lesion with no poor prognosticfactors.Case Rep Endocrinol,2013,2013:719304.
[4]薛金才,刘勤江,田尤新,侯小峰.BRAFV600E及TERT启动子突变在甲状腺微小乳头状癌风险评估中的价值.中国癌症杂志,2018,28(5):335-341.
[5]Tufano RP,Teixeira GV,Bishop J,Carson KA,Xing M.BRAFmutation in papillary thyroid cancer and its value in tailoring initial treatment:a systematicreview and meta-analysis.Medicine(Baltimore),2012,91(5):274-286.
[6]Xing M,Alzahrani AS,Carson KA,Viola D,Elisei R,Bendlova B,Yip L,Mian C,Vianello F,Tuttle RM,Robenshtok E,Fagin JA,Puxeddu E,Fugazzola L,Czarniecka A,Jarzab B,O’Neill CJ,Sywak MS,Lam AK,Riesco-Eizaguirre G,Santisteban P,Nakayama H,Tufano RP,Pai SI,Zeiger MA,Westra WH,Clark DP,Clifton-Bligh R,Sidransky D,Ladenson PW,Sykorova V.Association between BRAF-V600E mutation and mortality in patients with papillary thyroid cancer.JAMA,2013,309(14):1493-501.
[7]Miyauchi A.Clinical trials of active surveillance of papillary microcarcinoma of the thyroid.World J Surg,2016,40(3):516-522.
[8]Haugen BR,Alexander EK,Bible KC,Doherty GM,Mandel SJ,Nikiforov YE,Pacini F,Randolph GW,Sawka AM,Schlumberger M,Schuff KG,Sherman SI,Sosa JA,Steward DL,Tuttle RM,Wartofsky L.2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer:The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.Thyroid,2016,26(1):1-133.
[9]Cibas ES,Ali SZ.The 2017 Bethesda System for reporting thyroid cytopathology.Thyroid,2017,27(11):1341-1346.
[10]Virk RK,Van Dyke AL,Finkelstein A,Prasad A,Gibson J,Hui P,Theoharis CG,Carling T,Roman SA,Sosa JA,Udelsman R,Prasad ML.BRAFV600E mutation in papillary thyroid microcarcinoma:a genotype-phenotype correlation.Mod Pathol,2013,26(1):62-70.
[11]Lesnik D,Cunnane ME,Zurakowski D,Acar GO,Ecevit C,Mace A,Kamani D,Randolph GW.Papillary thyroid carcinoma nodal surgery directed by a preoperative radiographic map utilizing CT scan and ultrasound in all primary and reoperative patients.Head Neck,2014,36(2):191-202.
[12]Zhang LY,Liu ZW,Liu YW,Gao WS,Zheng CJ.Risk factors for nodal metastasis in cN0 papillary thyroid microcarcinoma.Asian Pac J Cancer Prev,2015,16(8):3361-3363.
[13]Elsayed AA,Murdoch C,Murray S,Bashir K.Can thyroid surgery be decided based on ultrasonographic findings,irrespective of cytopathological findings?Five-year retrospective study in a district general hospital.Clin Radiol,2017,72(2):170-174.
[14]李征毅,赵永胜,李锋,刘伟宗,关弘.甲状腺乳头状癌BRAF基因突变与超声及病理特征相关性研究.新医学,2018,49(11):828-833.
[15]刘燕,龚业琼,吴晓莉,申俊玲,李祥.常规超声与B超引导下穿刺细胞学检查在诊断小病灶甲状腺结节中的对比.中国老年学,2017,37(14):3564-3566.
[16]Chiofalo MG,Signoriello S,Fulciniti F,Avenia N,Ristagno S,Lombardi CP,Nicolosi A,Pelizzo MR,Perigli G,Polistena A,Panebianco V,Bellantone R,CalòPG,Boschin IM,Badii B,Di Maio M,Gallo C,Perrone F,Pezzullo L.Predictivity of clinical,laboratory and imaging findings in diagnostic definition of palpable thyroidnodules.A multicenter prospective study.Endocrine,2018,61(1):43-50.
[17]Rosove MH,Peddi PF,Glaspy JA.BRAFV600E inhibition in anaplastic thyroid cancer.N Engl J Med,2013,368(7):684-685.
[18]Xing M,Alzahrani AS,Carson KA,Shong YK,Kim TY,Viola D,Elisei R,BendlováB,Yip L,Mian C,Vianello F,Tuttle RM,Robenshtok E,Fagin JA,Puxeddu E,Fugazzola L,Czarniecka A,Jarzab B,O’Neill CJ,Sywak MS,Lam AK,Riesco-Eizaguirre G,Santisteban P,Nakayama H,Clifton-Bligh R,Tallini G,Holt EH,SykorováV.Association between BRAFV600E mutation and recurrence of papillary thyroid cancer.JClin Oncol,2015,33(1):42-50.--
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