弥漫性半球胶质瘤临床病理特征及分子病理特征分析  

Analysis of clinicopathological features and molecular pathological features of diffuse hemispheric glioma

作　　者：张立英 常青 杜江[1] Zhang Liying;Chang Qing;Du Jiang(Neuropathology Unit,Beijing Neurosurgical Institute,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China;Department of Pathology,Daxing Teaching Hospital,Capital Medical University,Beijing 102600,China)

机构地区：[1]北京市神经外科研究所,首都医科大学附属北京天坛医院神经病理中心,100070 [2]首都医科大学大兴教学医院病理科,北京102600

出　　处：《神经疾病与精神卫生》2024年第5期333-340,共8页Journal of Neuroscience and Mental Health

摘　　要：目的探讨弥漫性半球胶质瘤(DHG)的临床病理特征及分子病理特征。方法选取2021年1月—2023年5月于首都医科大学附属北京天坛医院神经外科接受手术切除或立体定向活检的27例DHG患者为研究对象,收集患者临床资料并进行随访。采用苏木素-伊红染色及免疫组织化学染色检测肿瘤细胞特征性的蛋白表达;采用二代测序+焦磷酸测序的方法检测肿瘤分子病理学特征。结果27例DHG患者的中位发病年龄为22.5岁;男性占59.3%(16/27);24例肿瘤主要位于单侧额、顶、颞叶,仅3例位于双侧大脑半球。组织病理学结果显示,27例肿瘤形态学上5例呈星形细胞瘤形态,17例呈胶质母细胞瘤形态,1例呈胶质母细胞瘤伴节细胞样分化,4例呈原始神经外胚层肿瘤形态。免疫组化染色结果显示,27例肿瘤胶质纤维酸性蛋白染色均为弥漫阳性,少突胶质细胞转录因子2蛋白阴性表达,α-地中海贫血/精神发育迟滞综合征X染色体相关基因表达缺失,p53蛋白呈错义突变或无义突变表达,异柠檬酸脱氢酶1 R132H、异柠檬酸脱氢酶2 R172K、H3K27M、BRAF V600E蛋白均呈阴性表达,24例肿瘤细胞核不同程度地表达H3.3G34R蛋白,3例肿瘤弥漫性表达H3.3G34V蛋白。Ki67增殖指数3%~80%不等。分子病理学检测结果显示,所有肿瘤均出现H3F3A基因H3.3 G34(35)突变,23例伴ATRX缺失,27例均伴TP53突变。随访2~24个月,其中5例在确诊10~24个月后死亡,中位无进展生存期为6.5个月,中位总生存时间为11个月,5例失访。结论DHG恶性程度高,尽管全切或近全切病变加放疗或化疗,患者仍很快复发进展或死亡。因此,对于DHG进行免疫组化及分子病理检测是必要的,更有利于对DHG患者的积极治疗和预后评估。Objective To investigate the clinicopathological and molecular pathological features of diffuse hemispheric glioma(DHG).Methods A total of 27 DHG patients who underwent surgical resection or stereotactic biopsy at the Neurosurgery Department of Beijing Tiantan Hospital Affiliated to Capital Medical University from January 2021 to May 2023 were selected as the study subjects.Clinical data of the patients were collected and followed up.Hematoxylin eosin staining and immunohistochemical staining were used to detect the characteristic protein expression in tumor cells.The next generation sequencing and pyrosequencing methods were used to detect the molecular pathology characteristics of tumors.Results The median age of onset for 27 DHG patients was 22.5 years old;59.3%(16/27)were males;24 cases of tumors mainly located in unilateral frontal,parietal,and temporal lobes,with only 3 cases located in bilateral cerebral hemispheres.The histopathological results showed that 5 out of 27 tumors had the morphology of astrocytoma,17 had the morphology of glioblastoma,1 had glioblastoma with ganglion like differentiation,and 4 had the morphology of primitive neuroectodermal tumors.The immunohistochemical staining results showed that all 27 cases of tumor glial fibrillary acidic protein staining were diffuse positive,and transcription factor 2 protein expression in oligodendrocytes was negative,α-the expression of X-chromosome related genes in thalassemia/mental retardation syndrome was missing,and p53 protein was expressed with missense or nonsense mutations.Isocitrate dehydrogenase 1 R132H,isocitrate dehydrogenase 2 R172K,H3K27M,and BRAF V600E proteins were all negative.24 cases of tumor cell nuclei expressed H3.3G34R protein to varying degrees,and 3 cases of tumors diffusely expressed H3.3G34V protein.The Ki67 proliferation index varied from 3%-80%.The molecular pathological results showed that all tumors had H3F3A gene H3.3 G34(35)mutations,23 cases with ATRX deletion,and 27 cases with TP53 mutations.Follow up for 2-24 mont

关 键 词：神经胶质瘤 胶质母细胞瘤 星形细胞瘤 病理学 弥漫性半球胶质瘤 原始神经外胚层肿瘤 

分 类 号：R739.41[医药卫生—肿瘤]