儿童和青少年甲状腺癌的临床病理特点及预后影响因素研究

Clinicopathological features and prognoses for thyroid carcinoma in children and adolescents

目的探讨儿童及青少年甲状腺癌与成人甲状腺癌临床病理特征的差异,分析儿童及青少年甲状腺癌的基因突变情况、预后情况及其危险因素。方法本研究为回顾性研究,纳入2007年6月至2021年12月空军军医大学西京医院收治的84例儿童及青少年(≤20岁)甲状腺癌患者为观察组,纳入医院同期收治的100例成人甲状腺癌患者为对照组,分析两组患者临床病理特征。根据观察组患者BRAFV600E基因突变情况分为突变组和野生组,分析BRAFV600E基因突变与观察组患者临床病理特征的相关性。根据观察组患者是否复发分为复发转移组和无复发转移组,分析影响观察组患者复发转移的危险因素。结果观察组84例患者与对照组100例患者相比,两组在多发病灶(36.9%比22.0%)、双侧病灶(34.5%比11.0%)、病理诊断(甲状腺乳头状癌81.0%比31.5%;甲状腺微小乳头状癌11.9%比60.5%;其他7.1%比0%)、淋巴转移(67.9%比42.0%)方面差异有统计学意义(P<0.05),在性别(男性22.6%比28.0%;女性77.4%比72.0%)、血型(A型38.1%比26.0%;B型21.4%比30.0%;AB型35.7%比36.0%;O型4.8%比8.0%)、手术类型(全切手术84.5%比80.0%;部分/近全切15.5%比20.0%)、BRAFV600E/TERT/NRAS基因突变方面差异没有统计学意义(P>0.05)。观察组患者中,存在BRAFV600E基因突变的患者淋巴结转移率显著高于无BRAFV600E基因突变患者(χ^(2)=6.497,P=0.011)。随访发现,观察组11例出现复发转移,对照组无一例复发,差异有统计学意义(P<0.01)。多因素分析结果显示,与≤10岁患者相比,11~20岁的患者术后无进展生存时间明显延长(P=0.014)。随访至2022年10月31日,两组均无一例死亡。结论儿童及青少年甲状腺癌多发病灶、双侧病灶及淋巴结转移比例明显高于成人甲状腺癌,甲状腺微小乳头状癌的比例明显低于成人甲状腺癌;儿童及青少年甲状腺癌中有BRAFV600E突变者的淋巴结转移率显著高于无BRAFV600E突变者;年龄是儿童及青少年甲状腺癌患者无复发生存的独立影响因素。

Objective To explore the clinicopathologic differences between thyroid cancer(TC)in children and adolescents versus adults and examine gene mutation,prognosis and risk factors of TC in children and adolescents.Methods For this retrospective study,84 TC children and adolescents aged≤20 years hospitalized from June 2007 to December 2021 were included as observation group while 100 adult TC in-patients during the same period as control group.The similarities and differences of clinicopathological characteristics between two groups were compared.According to the status of gene mutation in observation group,they were divided into BRAFV600E gene mutation and wild groups.Correlation was examined between BRAFV600E mutation and clinicopathologic features of TC children and adolescents.Observation group were divided into recurrence and metastasis group and non-recurrence and metastasis group according to whether or not there was recurrence or not.And the risk factors affecting the recurrence and metastasis of TC in children and adolescents were explored by univariate and multivariate analyses.Results The number of multiple lesions(36.9%vs.22.0%),the number of bilateral lesions(34.5%vs.11.0%),pathological diagnosis(81.0%vs.31.5%for papillary thyroid carcinoma;Thyroid micropapillary carcinoma 11.9%vs.60.5%;Other 7.1%vs.0%),lymphatic metastasis(67.9%vs.42.0%)were statistically significant(P<0.05),and gender(22.6%vs.28.0%;Female 77.4%vs.72.0%),blood type(A 38.1%vs.26.0%;Type B 21.4%vs.30.0%;Type AB 35.7%vs.36.0%;Type O 4.8%vs.8.0%),type of surgery(total resection 84.5%vs.80.0%);There was no significant difference in BRAFV600E/TERT/NRAS mutation(P>0.05).In the observation group,the lymph node metastasis rate in patients with BRAFV600E gene mutation was significantly higher than that in patients without BRAFV600E gene mutation(χ^(2)=6.497,P=0.011).Follow-up showed that 11 patients in the observation group had recurrence and metastasis after operation,while none in the control group.The recurrence and metastasis rate in the observation group was 13.1%higher than that in the control group,and the difference was statistically significant(P<0.01).The observation group was divided into recurrence and metastasis group and no recurrence and metastasis group.The results of multivariate analysis showed that age was an independent influencing factor for postoperative recurrence and metastasis(P=0.014).Follow-up to October 31,2022,84 cases in the observation group and 100 cases in the control group had no death.Conclusion The proportion of multiple lesions,bilateral lesions and lymph node metastasis is significantly higher in children and adolescents with TC than that in adults with TC.The proportion of papillary thyroid microcarcinoma is significantly lower than that in adults with TC.Lymph node metastasis rate in children and adolescents with TC with BRAFV600E mutation is significantly higher than that in wild-type patients.And age is an independent factor affecting recurrence-free survival in children and adolescents with TC.