Li J, Ma Y Y, Feng J, Zhao D, Ding F, Tian L, Chen R, Zhao Rui
Department of Pathology, Children's Hospital of Fudan University, Shanghai 201102, China Department of Pathology, Xi'an Children's Hospital, Xi'an Jiaotong University, Xi'an 710043, China.
Department of Pathology, Children's Hospital of Fudan University, Shanghai 201102, China.
Zhonghua Bing Li Xue Za Zhi. 2022 Apr 8;51(4):319-325. doi: 10.3760/cma.j.cn112151-20210830-00625.
To investigate the clinicopathological features of pediatric diffuse midline glioma with H3K27 alteration and to analyze their relationship with prognosis. Forty-one cases of childhood diffuse midline glioma with H3K27 alteration were collected at Children's Hospital of Fudan University (39 cases) and Xi'an Children's Hospital (2 cases), from July 2016 to July 2020. The clinical manifestations, imaging data, histopathology, immunohistochemical phenotype and molecular genetics features, tumor size, site and histological grading were evaluated. Among the 41 cases, 21 were males and 20 females, the age of onset was 3-14 years, the average and median age was 7.6 years and 7.0 years, respectively. The tumor sites were brain stem (=36) and other locations (=5). The clinical manifestations were dizziness, gait disturbance, and limb weakness, etc. The MRI features were variable. The histology varied from low-grade to high-grade glioma with neuron differentiation. Immunohistochemistry showed that the tumor cells expressed H3K27M, GFAP, and Olig2. Genetic study showed that 76% (16/21) of tumors had H3F3A gene mutation, mostly accompanied by TP53 (62%, 13/21) missense mutation; five tumors (24%, 5/21) had HIST1H3B gene mutation, accompanied by missense mutations in ACVR1 and PI3K pathway-related gene PIK3CA (4/5) and PIK3R1 (1/5) mutations. The prognosis was dismal with only one alive and others died. The average and median overall survival time was 7 months and 4 months, respectively. Cox multivariate regression analysis showed that age, tumor location, radiologically maximum tumor diameter, histologic grading, and surgical methods were not significantly associated with overall survival rate (>0.05). Pediatric diffuse midline gliomas with H3K27 alteration have unique clinicopathological and genetic characteristics. The prognosis is poor. The tumor location and histopathologic grading are not related to prognosis. New specific drugs and comprehensive treatment are needed to improve the prognosis.
探讨伴有H3K27改变的儿童弥漫性中线胶质瘤的临床病理特征，并分析其与预后的关系。2016年7月至2020年7月，复旦大学附属儿科医院（39例）和西安市儿童医院（2例）共收集41例伴有H3K27改变的儿童弥漫性中线胶质瘤病例。对其临床表现、影像学资料、组织病理学、免疫组化表型及分子遗传学特征、肿瘤大小、部位及组织学分级进行评估。41例中，男性21例，女性20例，发病年龄3～14岁，平均年龄7.6岁，中位年龄7.0岁。肿瘤部位为脑干（=36例）和其他部位（=5例）。临床表现为头晕、步态障碍、肢体无力等。MRI表现多样。组织学类型从低级别到高级别胶质瘤伴神经元分化。免疫组化显示肿瘤细胞表达H3K27M、GFAP和Olig2。基因研究表明，76%（16/21）的肿瘤有H3F3A基因突变，大多伴有TP53（62%，13/21）错义突变；5例肿瘤（24%，5/21）有HIST1H3B基因突变，伴有ACVR1错义突变及PI3K通路相关基因PIK3CA（4/5）和PIK3R1（1/5）突变。预后不佳，仅1例存活，其余均死亡。平均总生存时间和中位总生存时间分别为7个月和4个月。Cox多因素回归分析显示，年龄、肿瘤部位、影像学最大肿瘤直径、组织学分级及手术方式与总生存率无显著相关性（>0.05）。伴有H3K27改变的儿童弥漫性中线胶质瘤具有独特的临床病理和基因特征。预后较差。肿瘤部位和组织病理学分级与预后无关。需要新的特效药物和综合治疗以改善预后。
