Histologisch als Astrozytom WHO Grad 2/3 erscheinende Glioblastome

Glioblastomas are conventionally diagnosed based on histopathological, immunohistochemical, and molecular genetic characteristics. However, under the current WHO classification for CNS tumors, the presence of typical histopathological features such as necrosis and vascular proliferation in a malignant astrocytoma is no longer required for a glioblastoma diagnosis if a TERT mutation or EGFR amplification is detected in absence of IDH1/2 mutations. In this study, we compared the overall survival (OS) of histologically defined glioblastoma (GBM) with those lacking necrosis and vascular proliferation, referred to as molecular glioblastomas (molGBM).

We identified patients with histologically graded IDH-wildtype astrocytomas (WHO grade 2/3) harboring a TERT mutation or EGFR amplification (molGBM) and compared their demographic and clinical characteristics with those of a randomly selected control group of histologically defined glioblastoma (GBM) patients. The primary endpoint was OS in both groups. To further refine our analysis, we also compared molGBM to a second control group consisting of patients with IDH-mutant astrocytomas with similar histological grading (IDHmut-AST °2/3).

A total of 31 patients with molGBM were identified, including 12 with WHO grade 2 (molGBM°2) and 19 with WHO grade 3 histology (molGBM°3). The control group consisted of 34 randomly selected GBM patients. No significant differences were observed between groups regarding sex (p = 0.44) or age (p = 0.67). The Karnofsky Performance Index was comparable across groups (p = 0.74). Although the median OS was longer in the molGBM group (516 days) compared to the GBM group (328 days), this difference did not reach significance (p = 0.07). Additionally, subgroup comparisons between molGBM°2, molGBM°3, and GBM did not reveal significant OS differences (molGBM°2 vs. GBM: p = 0.09; molGBM°3 vs. GBM: p = 0.19; molGBM°2 vs. molGBM°3: p = 0.24). However, OS in molGBM was significantly shorter than in IDHmut-AST of similar grades (molGBM °2 vs. IDHmut-AST °2: p = 0.004; molGBM °3 vs. IDHmut-AST °3: p < 0.0001).

Our data support the last WHO update on CNS tumor classification and confirm that astrocytomas with a TERT mutation or EGFR amplification, and without necrosis and vascular proliferation, exhibit clinical behavior similar to that of glioblastoma.