成人H3K27M突变弥漫中线胶质瘤的临床、影像学、病理学表现及治疗与预后  

Clinical and pathological features,imaging findings,treatment and prognosis of adult H3K27M-mutant diffuse midline gliomas

作　　者：王强 王汉东 潘灏 孙康健 WANG Qiang;WANG Han-dong;PAN Hao(Department of Neurosurgery,Jinling Hospital,School of Meeicine,Nanjing University,Nanjing 210002,China)

机构地区：[1]中国人民解放军东部战区总医院(南京大学医学院附属金陵医院)神经外科,南京210002

出　　处：《临床神经外科杂志》2021年第5期523-529,534,共8页Journal of Clinical Neurosurgery

基　　金：江苏省“科教强卫”工程临床重点学科建设基金(ZDXKB2016023);江苏省青年医学人才项目(QNRC2016898)。

摘　　要：目的探讨成人H3K27M突变弥漫中线胶质瘤(DMG)患者的临床、影像、病理学表现及治疗与预后。方法回顾性分析11例成人H3K27M突变DMG患者的临床资料。分析患者的影像学表现、组织病理、分子病理特征及随访结果;并与同期的20例H3K27M野生型DMG、37例IDH野生型非中线胶质母细胞瘤(GBM)患者的临床特点进行比较,应用Kaplan-Meier法做生存分析比较预后。结果本组患者占同期胶质瘤的2.4%,占同期中线胶质瘤的11.9%;临床表现为头痛、恶心呕吐等颅高压症状,或为肿瘤累及下丘脑出现的口干、多饮、多尿,累及脑干出现肢体无力等。本组患者的年龄[(32±12)岁]明显小于H3K27M野生型DMG组[(47±12)岁]和IDH野生型非中线GBM组患者[(60±11)岁](P=0.004,P<0.001)。肿瘤多发生于丘脑(54.5%)。影像学表现为肿瘤T2WI、DWI等信号,部分为稍高信号,增强扫描多呈不均匀强化;瘤内囊变以小灶状囊变多见,瘤周无或轻度水肿;多呈不均匀高灌注;无特征性。肿瘤的手术全切率低(10%)。组织病理学特征可为低级别表现(45.5%),分子病理缺乏IDH突变、TERT启动子区突变及EGFR突变或扩增,MGMT启动子区甲基化均为阴性,可有BRAF V600E突变(9.1%)及TP53突变(27.3%)。本组患者的中位PFS为10个月,中位OS为12个月,与IDH野生型非中线GBM患者中位PFS及OS(8个月,14个月)的差异均无统计学意义(P=0.709,P=0.107)。结论H3K27M突变DMG是一类发生于中线部位的高度恶性的肿瘤,成人亦可发生,缺乏典型临床、影像学表现,H3K27M蛋白免疫组化检测的灵敏度较高,H3基因突变检测可明确诊断。因其缺乏IDH突变及MGMT启动子甲基化,对放化疗不敏感,预后不良。Objective To summarize and discuss the clinical features,imaging findings,pathological features,treatment and prognosis of adult patients H3 K27 M-mutant diffuse midline gliomas(DMG).Methods The clinical data(imaging findings,histopathological and molecular pathological characteristics and follow-up results)of 11 cases of adult H3 K27 mutant DMG were analyzed retrospectively.The results were compared with 20 cases of H3 K27 M wild-type midline glioma and 37 cases of IDH wild-type non-midline glioblastoma.The overall survival differences between the groups were shown by Kaplan-Meier curve.Results The 11 cases of H3 K27 M mutant DMG accounted for 2.4%of glioma patients and 11.9%of midline gliomas during the same period.The clinical manifestations were mostly headache,nausea and vomiting and other symptoms of intracranial hypertension,or symptoms of polydipsia and polyuria presented by hypothalamus tumors,and limb dysfunction presented by brain stem tumors.The mean age of this group was(32±12)years old,which was significantly younger than H3 K27 M wild-type midline glioma(47±12 years)and IDH wild-type non-midline glioblastoma(60±11 years).Tumors mostly occurred in the thalamus(54.5%),lacking typical characteristic imaging findings showed mostly isointense were on T2 WI,DWI,some were slightly high signal,and the enhancement were mostly uneven enhancement.Small focal cysts were more common in intratumoral cysts,with no or mild edema around the tumor,mostly uneven high perfusion.Rare tumor gross total resection(10%).Histological features could be low-grade(45.5%),molecular pathology lacked IDH mutations,TERT promoter region mutations,and EGFR mutations or amplifications,MGMT promoter region methylation was negative,with 9.1%BRAF V600 E mutations and 27.3%TP53 mutations.The median PFS was 10 months,and the median OS was 12 months.There was no significant difference in median PFS and OS of H3 K27 M mutant diffuse midline glioma compared with that of IDH wildtype non-midline glioblastomas(8 months,P=0.709,14 months,P=0

关 键 词：H3K27M突变 弥漫中线胶质瘤 MGMTp非甲基化 预后 

分 类 号：R739.41[医药卫生—肿瘤]