甲状腺髓样癌上纵隔淋巴结转移的临床病理特征

Clinicopathological analysis of superior mediastinal lymph node metastases in medullary thyroid carcinoma

目的探讨甲状腺髓样癌上纵隔淋巴结转移(sMLNM)的临床病理特征。方法回顾性分析2012年5月至2021年1月于中国医学科学院肿瘤医院就诊的因影像学怀疑sMLNM而行手术治疗的甲状腺髓样癌患者的临床病理资料。根据术后病理结果将患者分成sMLNM组和无sMLNM组。收集患者的临床病理特征、术前术后降钙素(Ctn)和癌胚抗原(CEA)水平。影响因素分析采用logistic回归分析,采用绘制受试者工作特征(ROC)曲线确定术前Ctn和术前CEA预测sMLNM的最佳临界值。结果 94例患者中,sMLNM组69例,无sMLNM组25例。术前Ctn水平(P=0.003)、术前CEA水平(P=0.010)、远处转移(P=0.022)、淋巴结被膜外侵犯(P=0.013)、中央区淋巴结转移数(P=0.002)与sMLNM有关。多因素分析未发现与sMLNM有关的独立危险因素。术前Ctn预测sMLNM最佳临界值为1 500 pg/ml,曲线下面积为0.759(95%CI:0.646~0.872),术前Ctn诊断sMLNM的敏感度、特异度、阳性预测值、阴性预测值分别为61.2%、77.3%、89.1%和39.5%。胸骨劈开患者淋巴结转移率由高到低分别为2R区(82.4%,28/34)、2L区(58.8%,20/34)、4R区(58.8%,20/34)、3区(23.5%,8/34)、4L区(11.8%,4/34)。41例(43.6%,41/94)患者出现术后并发症,无围手术期死亡患者。14.8%(12/81)的患者术后1个月Ctn≤12 pg/ml,其中sMLNM患者5例。结论对于影像学高度可疑的sMLNM,联合术前Ctn诊断具有一定的临床指导意义,尤其是对于术前Ctn>1 500 pg/ml的患者;首次胸骨劈开术式清扫上纵隔淋巴结至少应包括上纵隔2~4区,以免残留病灶;手术的抉择和执行均需谨慎对待,虽然sMLNM患者术后达到生化治愈的概率低,但依然近41.7%的患者能在生化水平上从手术方案中获益。

Objective To investigate the clinicopathological characteristics of superior mediastinal lymph node metastases(sMLNM)in medullary thyroid carcinoma(MTC).Methods This retrospective analysis enrolled the patients who were treated for sMLNM of MTC in our hospital from May 2012 to January 2021.All patients were suspected of sMLNM due to preoperative imaging.According to the pathological results,the patients were divided into two groups named sMLNM group and the negative superior-mediastinal-lymph-node group.We collected and analyzed the clinical features,pathological features,pre-and post-operative calcitonin(Ctn),and carcinoembryonic antigen(CEA)levels of the two groups.Logistic regression analysis was used to analyze risk factors,and receiver operation characteristic(ROC)curves were drawn to determine the optimal cut-off values of preoperative Ctn and preoperative CEA for predicting sMLNM.Results Among the 94 patients,69 cases were in the sMLNM group and 25 cases were in the non-SMLNM group.Preoperative Ctn level(P=0.003),preoperative CEA level(P=0.010),distant metastasis(P=0.022),extracapsular lymph node invasion(P=0.013),the number of central lymph node metastases(P=0.002)were related to sMLNM,but the multivariate analysis did not find any independent risk factors.The optimal threshold for predicting sMLNM by pre-operative Ctn is 1500 pg/ml and AUC is 0.759(95%CI:0.646,0.872).The sensitivity,specificity,positive predictive value,and negative predictive value of diagnosis are 61.2%,77.3%,89.1%,39.5%,respectively.In patients who underwent mediastinal lymph node dissection through transsternal approach,the metastatic possibility of different levels from high to low were level 2R(82.3%,28/34),level 2L(58.8%,20/34),level 4R(58.8%,20/34),level 3(23.5%,8/34),level 4L(11.8%,4/34).Postoperative complications occurred in 41 cases(43.6%),and there was no perioperative death in all cases.14.8%(12/81)of the patients achieved biochemical complete response(Ctn≤12 pg/ml)one month after surgery,5 of these patients were in sMLNM group.Conclusions For patients who have highly suspicious sMLNM through imaging,combining with preoperative Ctn diagnosis can improve the accuracy of diagnosis,especially for patients with preoperative Ctn over 1500 pg/ml.The superior mediastinal lymph node dissection for the primary sternotomy should include at least the superior mediastinal levels 2-4 to avoid residual lesions.The strategy of surgery needs to be cautiously performed.Although the probability of biochemical cure in sMLNM cases is low,nearly 40%of patients can still benefit from the operation at the biochemical level.