巨细胞胶质母细胞瘤的临床病理观察及分子遗传分析  

Clinicopathological observation and molecular genetic analysis of giant cell glioblastoma

作　　者：邓绮玲 王芳[2] 赵宇骐 奚可欣 谢晓婷 赵卫 吴小延[2] DENG Qiling;WANG Fang;ZHAO Yuqi;XI Kexin;XIE Xiaoting;ZHAO Wei;WU Xiaoyan(BSL-3 Laboratory(Guangdong),Guangdong Provincial Key Laboratory of Tropical Disease Research,School of Public Health,Southern Medical University,Guangzhou 510515,China)

机构地区：[1]南方医科大学公共卫生学院,广东省热带病研究重点实验室,BSL-3实验室,广州510515 [2]中山大学肿瘤防治中心分子诊断科

出　　处：《临床神经外科杂志》2024年第4期418-423,共6页Journal of Clinical Neurosurgery

基　　金：广东省基础与应用基础研究基金项目(2020A1515010313)。

摘　　要：目的 探讨巨细胞胶质母细胞瘤(GCG)临床病理及分子遗传学特征。方法 回顾性分析2019年3月—2023年2月中山大学肿瘤防治中心收治的3例GCG患者的临床病理资料及分子遗传学特征,并结合相关文献进行复习。结果 3例GCG中,1例位于额叶,2例位于颞叶。组织学特征多为奇异性具有丰富嗜酸性细胞质的多核巨细胞,偶尔伴有丰富的网状蛋白纤维。免疫组织化学结果显示,2例肿瘤细胞表达GFAP、ATRX、INI1、p53;1例表达表皮生长因子受体(EGFR)、vimentin、Olig2;2例不表达CK;2例1p19q无缺失;Ki-67增殖指数分别为20%、40%和60%。分子检测发现3例异柠檬酸脱氢酶(IDH)1/2、2例H3F3A、2例BRAF及2例TERT为野生型;2例O^(6)-甲基鸟嘌呤甲基转移酶(MGMT)发生甲基化。2例进行二代基因测序,其中1例检测到TP53基因错义突变及7号染色体发生扩增。另外1例未检测到致病性基因变异。检测到RB1基因无义突变,TP53及POLE基因临床意义不明的错义突变。随访期间1例发生两次局部复发。结论 GCG是一种罕见的中枢神经系统肿瘤,具有巨型瘤巨细胞等独特的组织学形态,及一定特征的免疫表型及分子遗传学,需与类似形态的胶质肉瘤及伴有间变特征的多形性黄色瘤型星形细胞瘤等鉴别。Objective To investigate clinicopathological and molecular genetic characteristics of giant cell glioblastoma(GCG).Methods The clinical data,and molecular genetics of 3 patients with GCG admitted to Department of Molecular Diagnosis,Sun Yat-sen University Cancer Center from March 2019 to February 2023 were analyzed retrospectively,and the relevant literature were reviewed.Results Among the 3 cases of GCG,1 was located in the frontal lobe and 2 were located in the temporal lobe.Histological features were heterogeneous multinucleated giant cells with rich eosinophilic cytoplasm,occasionally accompanied by rich reticular protein fibers.Immunohistochemical results showed that GFAP,ATRX,INI1 and p53 were positive in 2 tumor cells.Epidermal growth factor receptor(EGFR),vimentin and Olig2 were positive in 1 case.2 cases were negative for CK.1p19q was absent in 2 case.Ki-67 proliferation index was 20%,40% and 60%,respectively.Wild-type was found in 3 cases of isocitrate dehydrogenase(IDH)1/2,2 case of H3F3A,2 case of BRAF and 2 case of TERT.O~6-methylguanine-DNA methyltransferase(MGMT) occurred in 2 cases.Second generation gene sequencing was performed in 2 cases,TP53 missense mutation and amplification of chromosome 7 were detected in 1 case.Another case didn't detect the pathogenic gene variation.Nonsense mutation of RB1 gene and missense mutation of TP53 and POLE gene were detected.Two local relapses occurred during the follow-up period.Conclusions GCG is a rare central nervous system tumor with unique histological morphology such as giant cells,as well as certain immune phenotypes and molecular genetics.It needs to be differentiated from glioblastoma with similar morphology and pleomorphic yellow tumor type astrocytoma with interstitial features.

关 键 词：巨细胞胶质母细胞瘤 临床病理 分子遗传学 免疫组化学 鉴别 

分 类 号：R739.41[医药卫生—肿瘤]