Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, South Korea.
Department of Pathology, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, South Korea.
Brain Pathol. 2020 Mar;30(2):235-245. doi: 10.1111/bpa.12782. Epub 2019 Oct 7.
The extremely invasive phenotypes and genotypes related to progression of gliomatosis cerebri (GC) remain unclear although GC has been removed as an independent entity from the 2016 WHO classification. Hence, categorization of GC under the current WHO molecular classification is essential, and the molecular subgroups that might contribute to GC progression should be compared with the histopathological differences between initial and new lesions identified during follow-up. Analyses of IDH1/2 and TERTp mutations and 1p/19q co-deletion, and immunohistochemistry of IDH1-R132H, ATRX, p53 and galectin-3 were performed. Anaplastic astrocytoma, IDH-wildtype (AA-IDHwt) was the common molecular subgroup (52.8%), followed by diffuse astrocytoma, IDH-wildtype (DA-IDHwt) and AA, IDH-mutant (AA-IDHmt) (each 16.9%), DA-IDHmt (7.9%), glioblastoma (GBM)-IDHwt (3.3%) and GBM-IDHmt (2.2%). Approximately 92% of the AA-IDHwt lesions progressed to histologically confirmed GBM in the newly enhanced lesions harboring the TERTp mutation and expressing galectin-3. Similar to primary GBMs, GC-related GBMs that progressed from the IDHwt subgroups showed microvascular proliferation, palisading necrosis or thrombotic occlusion, implying that a subset of IDHwt subgroups may evolve to overt GBM. Molecular subgrouping did not provide the perfect prediction for the survival of GC patients. The AA-IDHwt group showed worse overall and progression-free survival (PFS) than the AA-IDHmt group. Biopsy plus radiotherapy, chemotherapy and temozolomide treatment for DA-IDHwt, and resection plus radiotherapy and temozolomide treatment for AA-IDHwt prolonged PFS. In conclusions, majority of GC was of the AA-IDHwt subgroup, which progressed to GBM. Molecular subgroups may assist in the selection of treatment modalities, because "GC pattern" still remains as a special growth of gliomas in WHO 2016 classification without established treatment guideline.
尽管脑胶质瘤病（GC）已从 2016 年 WHO 分类中被剔除为一个独立实体，但与 GC 进展相关的高度侵袭性表型和基因型仍不清楚。因此，在当前的 WHO 分子分类下对 GC 进行分类，以及比较在随访中发现的初始和新病变之间的组织病理学差异，是至关重要的。对 IDH1/2 和 TERTp 突变以及 1p/19q 共缺失进行分析，并进行 IDH1-R132H、ATR、p53 和半乳糖凝集素-3 的免疫组化分析。间变性星形细胞瘤，IDH 野生型（AA-IDHwt）是常见的分子亚型（52.8%），其次是弥漫性星形细胞瘤，IDH 野生型（DA-IDHwt）和 AA，IDH 突变型（AA-IDHmt）（各 16.9%），DA-IDHmt（7.9%），胶质母细胞瘤，IDH 野生型（GBM-IDHwt）（3.3%）和 GBM-IDHmt（2.2%）。大约 92%的 AA-IDHwt 病变在新增强病变中进展为具有 TERTp 突变和表达半乳糖凝集素-3的组织学证实的 GBM。与原发性 GBM 相似，从 IDHwt 亚组进展而来的 GC 相关 GBM 显示微血管增生、栅栏状坏死或血栓性闭塞，这表明 IDHwt 亚组的一部分可能演变为明显的 GBM。分子亚组分类并不能为 GC 患者的生存提供完美的预测。AA-IDHwt 组的总生存期和无进展生存期（PFS）均较 AA-IDHmt 组差。DA-IDHwt 行活检加放疗、化疗和替莫唑胺治疗，AA-IDHwt 行切除加放疗和替莫唑胺治疗可延长 PFS。总之，大多数 GC 为 AA-IDHwt 亚组，进展为 GBM。分子亚组可能有助于选择治疗方式，因为在 2016 年 WHO 分类中，“GC 模式”仍然是胶质瘤的一种特殊生长方式，没有既定的治疗指南。
