成人散在性胶质瘤包括了一组异质性的中枢神经系统肿瘤。最近几年，广泛的（表观）基因组学分析已经鉴定出几个胶质瘤亚组，其特征是IDH1/2和组蛋白H3基因突变。DKFZ v12.5脑肿瘤分类器鉴定出了一组被归类为“成人型散在性高级别胶质瘤，IDH-wildtype，亚型F（HGG-F）”的16个散在性胶质瘤。对所有病例进行了组织病理学鉴定、全外显子测序和临床数据复查。根据全基因组DNA甲基化数据的无监督t-分布随机邻近嵌入和聚类分析，HGG-F在表观遗传谱方面显示出了与已知的中枢神经系统肿瘤分离的特异性表观遗传特征。全外显子测序显示频繁出现TERT启动子突变（12/15例）、PIK3R1突变（11/16例）和TP53突变（5/16例）。放射学特征在14例中有9例（64%）显示出脑胶质瘤样病灶。组织病理学上，大多数病例被分类为散在性胶质瘤（7/16例，44%）或可疑为散在性胶质瘤浸润区域（5/16例，31%）。这些病例中没有一例显示微血管增生或坏死。14名有随访数据的患者的结果与IDH-wildtype胶质母细胞瘤相比较，进展无病生存中位数为58个月，总体生存中位数为74个月（P<0.0001）。我们的系列研究代表了一种新型成人型散在性胶质瘤，具有独特的分子和临床特征。重要的是，我们提供了证据表明，在没有进一步高级别胶质瘤形态学或分子学迹象的散在性胶质瘤中，应该将TERT启动子突变解释为临床放射学表现和表观遗传谱背景下的独立标记物，并不适用作胶质母细胞瘤，IDH-wildtype的独立标记物。版权所有©2023 Wolters Kluwer Health, Inc. 保留所有权利。

Diffuse gliomas in adults encompass a heterogenous group of central nervous system neoplasms. In recent years, extensive (epi-)genomic profiling has identified several glioma subgroups characterized by distinct molecular characteristics, most importantly IDH1/2 and histone H3 mutations. A group of 16 diffuse gliomas classified as "adult-type diffuse high-grade glioma, IDH-wildtype, subtype F (HGG-F)" was identified by the DKFZ v12.5 Brain Tumor Classifier. Histopathologic characterization, exome sequencing, and review of clinical data was performed in all cases. Based on unsupervised t-distributed stochastic neighbor embedding and clustering analysis of genome-wide DNA methylation data, HGG-F shows distinct epigenetic profiles separate from established central nervous system tumors. Exome sequencing demonstrated frequent TERT promoter (12/15 cases), PIK3R1 (11/16), and TP53 mutations (5/16). Radiologic characteristics were reminiscent of gliomatosis cerebri in 9/14 cases (64%). Histopathologically, most cases were classified as diffuse gliomas (7/16, 44%) or were suspicious for the infiltration zone of a diffuse glioma (5/16, 31%). None of the cases demonstrated microvascular proliferation or necrosis. Outcome of 14 patients with follow-up data was better compared to IDH-wildtype glioblastomas with a median progression-free survival of 58 months and overall survival of 74 months (both P<0.0001). Our series represents a novel type of adult-type diffuse glioma with distinct molecular and clinical features. Importantly, we provide evidence that TERT promoter mutations in diffuse gliomas without further morphologic or molecular signs of high-grade glioma should be interpreted in the context of the clinicoradiologic presentation as well as epigenetic profile and may not be suitable as a standalone marker for glioblastoma, IDH-wildtype.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.