H3 G34突变型弥漫性半球胶质瘤的临床和病理学特征分析

Clinical and pathological characteristics of H3 G34-mutant diffuse hemispheric glioma

目的 分析H3 G34突变型弥漫性半球胶质瘤(DHG-G34)的临床及分子病理特征等相关因素。方法 回顾性分析2018年1月至2022年11月经中山大学肿瘤防治中心确诊的13例DHG-G34患者的临床病理特征、影像学特征及分子病理特征。结果 13例DHG-G34患者中男性6例,女性7例,平均诊断年龄19.7岁(13~25岁)。组织形态上,13例均为胶质母细胞瘤(GBM)结构,其中1例部分区域含原始神经外胚层肿瘤(PNET)形态。免疫组织化学检测显示所有病例IDH1均为阴性;9例p53 (81.8%,9/11)强阳性;13例GFAP (100%,13/13)弥漫表达;6例Syn (75.0%,6/8)阳性表达;6例(46.2%,6/13) ATRX表达缺失;Ki-67阳性指数20%~80%。13例行Sanger检测均显示H3F3A基因发生G34突变(其中10例为G34R突变,3例为G34V突变);IDH1/2及TERT基因均为野生型;MGMT基因均发生突变。4例(36.4%,4/11)在治疗过程中发生颅内复发或转移。13例患者平均总生存时间26.1个月,中位总生存时间为22.1个月。13例患者的1年、2年、3年生存率分别为84.6%、46.2%、38.5%。结论 H3 G34突变型DHG患者多见于儿童和青少年,好发于大脑半球;组织学可表现为胶质母细胞瘤或原始神经外胚层肿瘤的世界卫生组织(WHO)4级样肿瘤。

Objective To describe the clinical and molecular pathological features of diffuse hemispheric glio-ma that are caused by H3 G34 mutation(DHG-G34).Methods Retrospective analysis was performed on the clinico-pathologic,imaging and molecular characteristics of 13 DHG-G34 patients who were diagnosed by Sun Yat-sen Univer-sity Cancer Center from January 2018 to November 2022.Results There were 6 males and 7 females among the 13 DHG patients.The average age at diagnosis was 19.7 years old(with the range of 13 to 25).The 13 cases were all glio-blastoma multiforme glioblastoma(GBM),and one of them included primitive neuroectodermal tumour(PNET)in some regions.Immunohistochemical tests showed that IDH1 was negative in all cases.p53 was strongly positive in 9 cases(81.8%,9/11);GFAP was diffusely expressed in 13 cases(100%,13/13);Syn was positive in 6 cases(75.0%,6/8);ATRX expression was absent in 6 cases(46.2%,6/13);The Ki-67 positive index was 20%to 80%.The H3F3A gene was discov-ered to contain a G34 mutation in all 13 cases(10 cases had a G34R mutation and 3 cases had a G34V mutation).IDH1/2 and TERT gene were determined to be wild-type,and MGMT gene was mutated.Four cases(36.4%,4/11)had intracranial recurrence or metastasis during treatment.The mean overall survival time of the 13 patients was 26.1 months,and the me-dian overall survival time was 22.1 months.Survival rates of 1,2,and 3 years were 84.6%,46.2%,and 38.5%,respec-tively.Conclusion The H3G34-mutant DHG is more common in children and adolescents and is more likely to occur in the cerebral hemisphere,histologically manifests as a World Health Organization(WHO)grade 4 tumor of glioblasto-ma or primitive neuroectodermal tumor.