具有间变特征的节细胞胶质瘤的病理学特征  

Clinicopathological characteristics of gangliogliomas with anaplastic morphology

作　　者：郭林霭 王雷明[1] 付永娟[1] 罗韬 樊晓彤[3,4] 赵莉红 姚小红[2] 朴月善 Guo Linai;Wang Leiming;Fu Yongjuan;Luo Tao;Fan Xiaotong;Zhao Lihong;Yao Xiaohong;Piao Yueshan(Department of Pathology,Xuanwu Hospital,Capital Medical University,Beijing Geriatric Medical Research Centre,Beijing 100053,China;Department of Pathology,Army Medical University(Third Military Medical University),Chongqing 400038,China;Department of Neurosurgery,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;National Center for Neurological Disorders,National Center for Neurological Disorders and Clinical Research Center for Epilepsy,Capital Medical University,Beijing 100053,China)

机构地区：[1]首都医科大学宣武医院病理科北京市老年病医疗研究中心,北京100053 [2]陆军军医大学(第三军医大学)第一附属医院病理科,重庆400038 [3]首都医科大学宣武医院神经外科,北京100053 [4]国家神经疾病医学中心首都医科大学癫痫临床诊疗与研究中心,北京100053

出　　处：《中华病理学杂志》2024年第6期585-591,共7页Chinese Journal of Pathology

基　　金：首都卫生发展科研专项-重点攻关项目(2022-1-1031);北京市临床重点专科建设项目。

摘　　要：目的探讨具有间变特征的节细胞胶质瘤(anaplastic ganglioglioma,AGG)的临床、影像学、病理学、分子遗传学及表观遗传学特征,以确定AGG是否为一种独特的肿瘤类型。方法从2015年1月至2023年7月首都医科大学宣武医院病理确诊的667例节细胞胶质瘤病例中筛选出9例AGG,回顾性收集临床、影像学、治疗和预后资料,并对其进行二代测序检测及甲基化聚类分析。结果9例患者中,男5例,女4例,中位年龄为8岁。癫痫发作(5/9)是主要的临床症状,影像学检查示3种表现形式,4例磁共振成像(MRI)表现为异常信号,占位效应不明显,可有轻度强化;2例MRI表现为囊实性混杂密度影伴瘤周水肿,病灶多见明显不均匀强化,占位效应明显;1例MRI表现为囊腔形成伴附壁结节,结节部分明显强化。所有病例中均存在能激活MAPK信号通路的突变,包括7例出现BRAF p.V600E突变,2例出现NF1突变。5例AGG同时存在其他突变,包括3例CDKN2A纯合性缺失,1例TERT启动子突变,1例H3F3A突变,还有1例携带PTEN突变。结论组织学诊断为AGG的肿瘤具有不同于节细胞胶质瘤的临床表型、基因突变谱及生物学行为。这些特征提示AGG可能是一种独特的肿瘤类型,需要进一步扩大病例数来验证。应全面结合临床、组织学及分子检测结果综合作出AGG的诊断,以指导治疗及预后判断。Objective To investigate the clinical,radiological,and pathological features of anaplastic gangliogliomas(AGGs)and to determine whether these tumors represent a distinct entity.Methods Consecutive 667 cases of ganglioglioma(GG)diagnosed at the Xuanwu Hospital,Capital Medical University,Beijing,China between January 2015 and July 2023 were screened.Among these cases,9 pathologically confirmed AGG cases were identified.Their clinical,radiological,treatment,and outcome data were analyzed retrospectively.Most of the tumor samples were subject to next-generation sequencing,while a subset of them were subject to DNA methylation profiling.Results Among the 9 patients,there were five males and four females,with a median age of 8 years.Epileptic seizures(5/9)were the most frequently presented symptom.Radiological examinations showed three types of radiological manifestations:four cases showed abnormal MRI signals with no significant mass effects and mild enhancement;two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema,which showed significant heterogeneous enhancement and obvious mass effects,and one case displayed cystic cavity formation with nodules on MRI,which showed evident enhancements.All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway,including seven with BRAF p.V600E mutation and two with NF1 mutation.Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations,including three with CDKN2A homozygous deletion,one with a TERT promoter mutation,one with a H3F3A mutation,and one with a PTEN mutation.Conclusions AGG exhibits a distinct spectrum of pathology,genetic mutations and clinical behaviors,differing from GG.Given these characteristics suggest that AGG may be a distinct tumor type,further expansion of the case series is needed.Therefore,a comprehensive integration of clinical,histological,and molecular analyses is required to correctly diagnose AGG.It will also help guide treatments and prognostication.

关 键 词：神经节神经胶质瘤 间变 序列分析 DNA DNA甲基化 癫痫 

分 类 号：R739.4[医药卫生—肿瘤]