细针穿刺洗脱液甲状腺球蛋白检测对甲状腺乳头状癌颈部淋巴结转移的诊断价值

Diagnostic value of thyroglobulin detection in washout fluid of fine-needle aspiration biopsy for cervical lymph node metastasis in papillary thyroid carcinoma

摘要:

背景与目的 目前判断甲状腺乳头状癌（PTC）颈部淋巴结转移主要依靠超声及细针穿刺抽吸活检细胞学检查（FNAC），但均存在主观性及局限性。本研究探讨超声引导下细针穿刺抽吸活检洗脱液中甲状腺球蛋白（FNA-Tg）检测在PTC患者颈部淋巴结转移中的应用价值。方法 回顾性分析术后病理确诊的144例PTC患者资料，术前均行血清甲状腺球蛋白（Tg）检测，可疑颈部淋巴结行超声引导下FNAC及FNA-Tg检测，以术后最终病理结果为金标准，比较FNAC、FNA-Tg及两者联合对PTC患者颈部淋巴结转移诊断的敏感度、特异度、准确性、阳性预测值及阴性预测值，并绘制各诊断方法的受试者特征（ROC）曲线，计算ROC曲线下面积（AUC），确定定量指标FNA-Tg最佳诊断阈值。结果 144例PTC患者共检测176枚淋巴结，最终经病理诊断PTC转移性淋巴结81枚，非转移性淋巴结95枚。转移性淋巴结组血清Tg、FNA-Tg分别为28.84（7.42~84.22）ng/mL、500（142.56~500）ng/mL，非转移性淋巴结组血清Tg、FNA-Tg分别为20.11（9.57~38.30）ng/mL、0.10（0.10~0.29）ng/mL，两组间血清Tg比较差异无统计学意义（Z=1.878，P=0.062），两组间FNA-Tg比较差异有统计学意义（Z=10.981，P<0.001）。FNA-Tg诊断PTC转移性淋巴结的ROC曲线AUC为0.964（95% CI=0.937~0.992，P<0.001），最佳诊断阈值为4.79 ng/mL，FNAC诊断PTC转移性淋巴结的ROC曲线AUC为0.840（95% CI=0.777~0.903，P<0.001）；FNA-Tg和FNAC两者联合诊断PTC转移性淋巴结的ROC曲线AUC为0.960（95% CI=0.927~0.994，P<0.001）。FNAC及FNA-Tg诊断PTC转移性淋巴结的诊断敏感度、特异度、准确性、阳性预测值及阴性预测值分别为81.48%、85.26%、83.52%、82.50%、84.38%和92.59%、93.68%、93.18%、92.59%、93.68%；FNA-Tg和FNAC两者联合应用时为96.30%、95.79%、96.02%、95.12%、96.81%。FNAC与FNA-Tg在敏感度、准确性及阴性预测值差异有统计学意义（χ²=4.432，P=0.035；χ²=7.798，P=0.005；χ²=4.228，P=0.040），在特异度及阳性预测值则差异无统计学意义（χ²=3.576，P=0.059；χ²=3.768，P=0.052），FNA-Tg和FNAC两者联合时各项诊断指标均有所提高。结论 FNA-Tg测定为客观定量诊断方式，对诊断PTC颈部淋巴结转移具有较高的诊断价值，且高于FNAC，FNA-Tg测定与FNAC联合应用时可进一步提高诊断效能。

Abstract:

Background and Aims The current diagnosis of neck lymph node metastasis in papillary thyroid carcinoma (PTC) relies mainly on ultrasound and fine-needle aspiration cytology (FNAC). However, both methods have subjectivity and limitations. This study was conducted to investigate the application value of detection of thyroglobulin in the washout fluid from fine-needle aspiration biopsy (FNA-Tg) under ultrasound guidance for cervical lymph node metastasis in PTC patients.Methods The data of 144 patients with pathologically confirmed PTC were retrospectively analyzed. Preoperatively, all patients underwent serum thyroglobulin (Tg) testing, and suspicious cervical lymph nodes were subjected to ultrasound-guided FNAC and FNA-Tg testing. The postoperative final pathological results were considered as the gold standard. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FNAC, FNA-Tg, and their combination in diagnosing neck lymph node metastasis in PTC patients were compared. Receiver operating characteristic (ROC) curves were plotted for each diagnostic method, and the area under the ROC curve (AUC) was calculated to determine the optimal diagnostic threshold for the quantitative parameter FNA-Tg.Results A total of 176 lymph nodes were examined in 144 PTC patients. Among them, 81 lymph nodes were diagnosed as metastatic PTC and 95 lymph nodes were non-metastatic. The serum Tg and FNA-Tg levels in the metastatic lymph node group were 28.84 (7.42-84.22) ng/mL and 500 (142.56-500) ng/mL, respectively. In the non-metastatic lymph node group, the serum Tg and FNA-Tg levels were 20.11 (9.57-38.30) ng/mL and 0.10 (0.10-0.29) ng/mL, respectively. There was no statistically significant difference in serum Tg between the two groups (Z=1.878, P=0.062), while there was a statistically significant difference in FNA-Tg between the two groups (Z=10.981, P<0.001). The AUC of ROC curve for FNA-Tg in diagnosing metastatic PTC lymph nodes was 0.964 (95% CI=0.937-0.992, P<0.001), with the optimal diagnostic cut-off value of 4.79 ng/mL. The AUC of ROC curve for FNAC in diagnosing metastatic PTC lymph nodes was 0.840 (95% CI=0.777-0.903, P<0.001). When FNA-Tg and FNAC were used together to diagnose metastatic PTC lymph nodes, the AUC of ROC curve was 0.960 (95% CI=0.927-0.994, P<0.001). The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value in diagnosing metastatic PTC lymph nodes were 81.48%, 85.26%, 83.52%, 82.50%, 84.38% for FNAC, and 92.59%, 93.68%, 93.18%, 92.59%, 93.68% for FNA-Tg, respectively. When FNA-Tg and FNAC were used together, the values were 96.30%, 95.79%, 96.02%, 95.12%, and 96.81%. There were statistically significant differences in sensitivity, accuracy, and negative predictive value between FNAC and FNA-Tg (χ²=4.432, P=0.035; χ²=7.798, P=0.005; χ²=4.228, P=0.040). However, there was no statistically significant difference in specificity and positive predictive value (χ²=3.576, P=0.059; χ²=3.768, P=0.052). and all diagnostic indicators were improved by the combination of FNA-Tg and FNAC.Conclusion FNA-Tg measurement is an objective quantitative diagnostic method that has high diagnostic value in detecting cervical lymph node metastasis in PTC. It is superior to FNAC, and when FNA-Tg measurement is combined with FNAC, it further enhances the diagnostic performance.