嗜铬细胞瘤/副神经节瘤患者临床特征与肿瘤病理特征的关系

The relationship between clinical characteristics and pathological features in patients with pheochromocytomas/paragangliomas

目的探讨嗜铬细胞瘤/副神经节瘤(PPGLs)患者临床特征与肿瘤病理特征的关系。方法病例系列研究。回顾性纳入2019年1月至2022年12月就诊于北京协和医院且术后病理诊断为单发原发灶PPGLs的患者。以Ki-67增殖指数3%为界值分为Ki-67<3%组及Ki-67≥3%组。分析PPGLs患者临床特征与肿瘤病理特征的关系。结果共纳入399例PPGLs患者,男177例,女222例,年龄[M(Q_(1),Q_(3))]为45.0(35.5,53.0)岁。其中226例起源于肾上腺(56.6%),104例起源于腹膜后(26.1%)。20.9%(27/129)的PPGLs患者携带有PPGLs易感基因胚系突变,以SDHB突变最为多见(10.1%,13/129)。302例PPGLs行Ki-67染色,Ki-67增殖指数[M(Q_(1),Q_(3))]为2.0%(1.0%,3.0%)。Ki-67<3%组194例,Ki-67≥3%组108例。与Ki-67<3%组相比,Ki-67≥3%组患者发病年龄更小(P=0.029)。与没有携带SDHB或Cluster 1A相关基因突变、^(131)I-间碘苄胍(^(131)I-MIBG)显像阳性或O-6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)免疫组化染色阴性的PPGLs患者相比,携带有SDHB突变或Cluster 1A相关基因突变、^(131)I-MIBG显像阴性或MGMT免疫组化染色阳性的PPGLs患者的Ki-67指数更高(均P<0.05)。与肾上腺嗜铬细胞瘤相比,腹膜后副神经节瘤携带SDHB突变的比例更大、甲氧基去甲肾上腺素(NMN)分泌型比例更高(均P<0.05)。与肾上腺嗜铬细胞瘤相比,头颈部副神经节瘤肿瘤最大径更小[3.0(1.9,3.8)cm比4.7(3.4,6.4)cm,P<0.001],Ki-67≥3%的比例更高(61.3%比33.8%,P=0.007)。结论发病年龄早、携带SDHB或Cluster 1A相关基因胚系突变、^(131)I-MIBG显像阴性或MGMT免疫组化染色阳性的PPGLs患者Ki-67指数更高。头颈部来源肿瘤通常较小,但增殖能力并不弱。

Objective To explore the correlation between clinical characteristics and pathological features in patients with pheochromocytoma/paraganglioma(PPGLs).Methods A case series study.A retrospective analysis was conducted on patients with single and primary PPGLs after postoperative pathological diagnosis who were admitted to Peking Union Medical College Hospital between January 2019 and December 2022.The patients were divided into the Ki-67<3%group and the Ki-67≥3%group with Ki-67 proliferation index of 3%as the threshold.The relationship between clinical and pathological characteristics of PPGLs was analyzed.Results A total of 399 PPGLs patients were included,with 177 males and 222 females,aged[M(Q_(1),Q_(3))]45.0(35.5,53.0)years.Among them,226(56.6%)cases originated from the adrenal gland,while 104 cases(26.1%)from the retroperitoneum.20.9%(27/129)of the patients were found to harbor germline mutations of susceptibility genes,with SDHB mutations being the most common(10.1%,13/129).The Ki-67 staining was performed on 302 cases,with a Ki-67 proliferation index[M(Q_(1),Q_(3))]of 2.0%(1.0%,3.0%).There were 194 cases in Ki-67<3%group and 108 cases in Ki-67≥3%group.Compared with the patients in Ki-67<3%group,the age of onset in Ki-67≥3%group was younger(P=0.029).Compared with the patients with paragangliomas without SDHB or Cluster 1A-related gene mutations,positive^(131)I-meta-iodobenzylguanidine(^(131)I-MIBG)imaging or negative O-6-methylguanine-DNA methyltransferase(MGMT)immunohistochemistry staining,those with SDHB or Cluster 1A-related gene mutations,negative^(131)I-MIBG imaging or positive MGMT immunohistochemistry staining had a higher Ki-67 index(all P<0.05).Compared with adrenal pheochromocytoma,retroperitoneal paragangliomas had a higher proportion of SDHB mutations and a higher proportion of normetanephrine(NMN)secretory types(all P<0.05).Compared with adrenal pheochromocytoma,the maximum diameter of head and neck paraganglioma tumors was smaller[3.0(1.9,3.8)cm vs 4.7(3.4,6.4)cm,P<0.001]and the proportion of Ki-67≥3%was higher(61.3%vs 33.8%,P=0.007).Conclusions PPGLs patients with earlier onset age,SDHB or Cluster 1A-related gene mutations,negative^(131)I-MIBG imaging,or positive MGMT immunohistochemistry staining tend to have a higher Ki-67 index.Head and neck tumors,though smaller,exhibit a higher proliferation potential.