From the Department of Pathology and Laboratory Medicine and Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases, University of Texas Health San Antonio, San Antonio, Texas, USA.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
J Neuropathol Exp Neurol. 2021 Apr 16;80(5):431-435. doi: 10.1093/jnen/nlab023.
Numerous recent studies have demonstrated that the vast majority of IDH-wildtype astrocytomas with WHO grade II/III histology have clinical outcomes equivalent to IDH-wildtype glioblastomas. This has called into question the existence of an IDH-wildtype lower-grade astrocytoma (LGA) category, and the cIMPACT-NOW study group has suggested 3 molecular features which, if present, warrant upgrading IDH-wildtype LGA to glioblastoma: EGFR amplification, 7+/10-, and TERT promoter mutation. Herein, we evaluate the clinical, histologic, and molecular features of IDH-wildtype low-grade astrocytomas, defined here as infiltrative adult astrocytoma lacking histologic features of glioblastoma (microvascular proliferation and/or necrosis), IDH1/2 mutation, and all 3 of the cIMPACT-NOW update 3 factors. Compared with their counterparts with cIMPACT-NOW features of glioblastoma (LGA-C+; n = 108), IDH-wildtype LGAs lacking these features (LGA-C0; n = 36) occur in significantly younger patients, are more frequently WHO grade II, have less total copy number variation distributed across the entire genome, less frequent homozygous deletion of CDKN2A, less frequent PTEN and PIK3CA alterations, and more frequent NF1 alterations. These results suggest that although rare, a "true" IDH-wildtype LGA category does exist, and has distinct clinical and molecular features consistent with relatively beneficial clinical outcomes in these patients.
大量近期研究表明，绝大多数组织学分级为 II/III 级且 IDH 野生型的星形细胞瘤与 IDH 野生型胶质母细胞瘤具有等效的临床结局。这使得 IDH 野生型低级别星形细胞瘤（LGA）类别是否存在受到质疑，cIMPACT-NOW 研究组提出了 3 种分子特征，如果存在这些特征，则应将 IDH 野生型 LGA 升级为胶质母细胞瘤：EGFR 扩增、7+/10-和 TERT 启动子突变。在此，我们评估了 IDH 野生型低级别星形细胞瘤的临床、组织学和分子特征，这里定义的 IDH 野生型低级别星形细胞瘤为缺乏胶质母细胞瘤组织学特征（微血管增生和/或坏死）、IDH1/2 突变以及 cIMPACT-NOW 更新 3 因素中的所有 3 种特征的浸润性成人星形细胞瘤。与具有 cIMPACT-NOW 胶质母细胞瘤特征的 IDH 野生型 LGAs（LGA-C+；n=108）相比，缺乏这些特征的 IDH 野生型 LGAs（LGA-C0；n=36）发生于年龄明显更小的患者中，更常为 WHO 分级 II 级，全基因组的总拷贝数变异分布较少，CDKN2A 纯合缺失的频率较低，PTEN 和 PIK3CA 改变的频率较低，而 NF1 改变的频率较高。这些结果表明，尽管罕见，但确实存在“真正的”IDH 野生型 LGA 类别，并且具有与这些患者相对良好的临床结局一致的独特临床和分子特征。
