Yang Q Y, Li M N, Chen T Y, Liu C, Li X, Shi Z M, Pan M H
Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Zhonghua Bing Li Xue Za Zhi. 2023 Apr 8;52(4):376-383. doi: 10.3760/cma.j.cn112151-20220926-00810.
To investigate the clinicopathological characteristics, pathological diagnosis and prognosis of diffuse midline glioma (DMG) with H3K27 alteration in adults. Twenty cases of H3K27-altered adult DMG diagnosed in the First Affiliated Hospital of Nanjing Medical University were enrolled from 2017 to 2022. All cases were evaluated by clinical and imaging presentations, HE, immunohistochemical staining and molecular genetics; and the relevant literature was reviewed. The ratio of male to female was 1∶1, and the median age was 53 years (range from 25 to 74 years); the tumors were located in the brainstem (3/20, 15%) and non-brainstem (17/20, 85%; three in thoracolumbar spinal cord and one in pineal region). The clinical manifestations were non-specific, mostly dizziness, headache, blurred vision, memory loss, low back pain, limb sensation and/or movement disorders, etc. Microscopically, the tumors showed infiltrative growth, with WHO grade 2 (3 cases), grade 3 (12 cases), and grade 4 (5 cases). The tumors showed astrocytoma-like and oligdendroglioma-like, pilocytic astrocytoma-like and epithelioid-like patterns. Immunohistochemically, the tumor cells were positive for GFAP, Olig2 and H3K27M, and H3K27me3 expression was variably lost. ATRX expression was lost in four cases, p53 was strongly positive in 11 cases. Ki-67 index was about 5%-70%. Molecular genetics showed p. k27m mutation in exon 1 of H3F3A gene in 20 cases; BRAF mutation in two cases: V600E and L597Q mutation in one case each. Follow up intervals ranged from 1 to 58 months, and the survival time for brainstem (6.0 months) and non-brainstem (30.4 months) tumors was significantly different (<0.05). DMG with H3K27 alteration is uncommonly found in adults, mostly occurs in non-brainstem, and can present in adults of all ages. Owing to the wide histomorphologic features, mainly astrocytic differentiation, routine detection of H3K27me3 in midline glioma is recommended. Molecular testing should be performed on any suspected cases to avoid missed diagnosis. Concomitant BRAF L597Q mutation and PPM1D mutation are novel findings. The overall prognosis of this tumor is poor, with tumors located in the brainstem showing worse outcome.
探讨成人H3K27改变的弥漫性中线胶质瘤（DMG）的临床病理特征、病理诊断及预后。收集2017年至2022年在南京医科大学第一附属医院确诊的20例H3K27改变的成人DMG病例。所有病例均通过临床和影像学表现、苏木精-伊红（HE）染色、免疫组织化学染色及分子遗传学进行评估，并复习相关文献。男女比例为1∶1，中位年龄为53岁（范围25至74岁）；肿瘤位于脑干（3/20，15%）和非脑干（17/20，85%；胸段和腰段脊髓3例，松果体区1例）。临床表现无特异性，多为头晕、头痛、视力模糊、记忆力减退、腰痛、肢体感觉和/或运动障碍等。显微镜下，肿瘤呈浸润性生长，世界卫生组织（WHO）分级为2级（3例）、3级（12例）和4级（5例）。肿瘤呈现星形细胞瘤样、少突胶质细胞瘤样、毛细胞型星形细胞瘤样和上皮样形态。免疫组织化学检查显示，肿瘤细胞GFAP、Olig2和H3K27M呈阳性，H3K27me3表达不同程度缺失。4例ATRX表达缺失，11例p53呈强阳性。Ki-67指数约为5% - 70%。分子遗传学检测显示，20例H3F3A基因第1外显子存在p.K27M突变；2例存在BRAF突变：1例为V600E突变，1例为L597Q突变。随访时间为1至58个月，脑干肿瘤（6.0个月）和非脑干肿瘤（30.4个月）的生存时间差异有统计学意义（<0.05）。H3K27改变的DMG在成人中少见，多发生于非脑干，可发生于各年龄段成人。由于组织形态学特征广泛，主要为星形细胞分化，建议对中线胶质瘤常规检测H3K27me3。对任何可疑病例均应进行分子检测以避免漏诊。BRAF L597Q突变与PPM1D突变并存是新发现。该肿瘤总体预后较差，位于脑干的肿瘤预后更差。
