H3和IDH野生型弥漫性儿童型高级别胶质瘤6例临床病理分析  

Clinicopathological analysis of 6 cases of diffuse paediatric-type high-grade glioma,H3-wildtype and IDH-wildtype

作　　者：王瑞芬[1] 管雯斌[1] 严敏骅 琚璐 韩蕙如 王立峰[1] WANG Ruifen;GUAN Wenbin;YAN Minhua;JU Lu;HAN Huiru;WANG Lifeng(Department of Pathology,Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属新华医院病理科,上海200092

出　　处：《临床与实验病理学杂志》2024年第5期484-489,共6页Chinese Journal of Clinical and Experimental Pathology

基　　金：国家卫健委能力建设和继续教育中心(BLC2023JJSJ008)。

摘　　要：目的探讨中枢神经系统H3和IDH野生型弥漫性儿童型高级别胶质瘤的临床病理学及分子特征。方法收集上海交通大学医学院附属新华医院病理科诊断的6例H3和IDH野生型弥漫性儿童型高级别胶质瘤的临床病理资料,采用免疫组化(全自动免疫组化染色仪)检测GFAP、Olig2、Syn、NeuN、IDH1、H3K27M等蛋白的表达,FISH法检测EGFR、MYCN基因扩增,Sanger测序检测IDH、H3F3A、TERT基因突变,并复习相关文献。结果本组6例患者年龄范围5~11岁,中位年龄7.5岁。其中男性2例,女性4例,男女比1∶2。临床症状表现为肢体乏力、偏瘫、呕吐、抽搐、视物模糊等。肿瘤发生部位:5例位于幕上,1例位于幕下脑干和小脑。组织学形态:3例表现为高级别胶质瘤形态学特征,其中2例伴有瘤巨细胞;2例表现为胚胎性肿瘤样特征,1例同时具有高级别胶质瘤及胚胎性肿瘤样形态学特点。5例伴有微血管增生和(或)坏死;1例间质黏液变/微囊形成。免疫表型:肿瘤细胞GFAP(6/6)和Olig2(6/6)部分或局灶阳性,Syn(3/6)和NeuN(1/6)局灶或散在阳性,IDH1、H3K27M、H3G34V和H3G34R均阴性,ATRX、H3K27me3、INI1、BRG1均弥漫阳性(6/6)。p53阳性5%~95%不等,Ki67增殖指数40%~90%。分子检测示6例均为IDH1/2和H3F3A野生型;2例MYCN扩增;2例EGFR扩增伴多倍体;1例同时伴有EGFR扩增和MYCN扩增;1例PDGFRA扩增。治疗及随访情况,术后放疗和(或)替莫唑胺化疗;3例于术后1~5个月死亡;2例存活,随访截至2024年1月,分别随访4个月和7个月;1例失访。结论H3和IDH野生型弥漫性儿童型高级别胶质瘤是一种高度恶性肿瘤,组织学表现为胶质母细胞瘤样或胚胎性肿瘤样特征,根据分子遗传学特征分为RTK1、RTK2、MYCN三种分子亚型,其中MYCN亚型预后最差。诊断时应注意与其他儿童型或成人型高级别胶质瘤及胚胎性肿瘤鉴别。Purpose To investigate the clinicopathological features and molecular features of diffuse paediatric-type high-grade glioma,H3-wildtype and IDH-wildtype(pHGG H3/IDH WT)of central nervous system.Methods The clinical and pathological data of 6 cases of pHGG H3/IDH WT diagnosed by Department of Pathology,Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine were retrospectively analyzed.The expression of GFAP,Olig2,Syn,NeuN,IDH1,H3K27M was detected by immunohistochemistry(automatic immunohistochemical staining device).The EGFR and MYCN gene amplification was detected by FISH.IDH,H3F3A and TERT gene mutations were detected by Sanger sequencing.The literatures were reviewed.Results The 6 patient’s age ranged from 5 to 11 years,with a median age of 7.5 years.Among them,there were 2 males and 4 females,with a male to female ratio of 1∶2.The clinical symptoms were limb weakness,hemiplegia,vomiting,convulsions,blurred vision and so on.Tumors were located in supratentorial brain for 5 cases and one in brain stem and cerebellum.Histologically,3 cases showed the morphological features of high-grade glioma,2 of which with giant cells.Two cases showed embryonal tumor-like features,and one had both high-grade glioma and embryonal tumor-like morphological features.Microvascular proliferation and/or necrosis were present in 5 cases.Myxoid/microcystic stroma was found in 1 case.By immunohistochemistrically,the tumor cells were partially or focally positive for GFAP(6/6)and Olig2(6/6),focally positive for Syn(3/6)and NeuN(1/6),and negative for IDH1,H3K27M,H3G34V and H3G34R.ATRX,H3K27me3,INI1 and BRG1 were diffusely positive(6/6).The positive rate of p53 was 5%-95%,and Ki67 proliferation index was 40%-90%.Molecular analysis showed that all 6 cases were IDH1/2 and H3F3A wild-type.MYCN amplification was observed in 2 cases.Two cases of EGFR amplification with polyploidy;one case had both EGFR amplification and MYCN amplification.PDGFRA amplification was observed in one case.For treatment and follow-up,the p

关 键 词：弥漫性儿童型高级别胶质瘤 H3野生型 IDH野生型 鉴别诊断 

分 类 号：R739.41[医药卫生—肿瘤]