JS04.6.A CLINICAL PRESENTATION OF “MOLECULAR GLIOBLASTOMA” IS DIFFERENT COMPARED TO “HISTOLOGICAL GLIOBLASTOMA”, BUT OUTCOME IS THE SAME, REGARDLESS OF GRADE OR PRESENCE OF ONLY ATERT PROMOTER MUTATION

BACKGROUND In the 2021 revised WHO CNS, IDH1/2-wildtype (IDHwt) gliomas with histological features of lower grade glioma, but with a TERT-promotor (TERTp) mutation, and/or EGFR amplification, and/or combined gain of chromosome 7 and loss of chromosome 10 (7+/10-), are now classified as IDHwt glioblastoma. These formerly labeled “molecular glioblastomas” (m-GBMs) are not separated from histologically defined glioblastomas (h-GBMs). However, there is still discussion whether these gliomas are truly the same in terms of first presentation and survival especially in the presence of grade 2 histology. We expanded and re-analyzed a cohort of m-GBMs and had the histological grade re-evaluated, to investigate the impact of histological grade in m-GBMs, and also specifically in patients with isolated TERTp mutations. MATERIAL AND METHODS We identified cases from 3 Dutch hospitals, which were initially histologically classified as grade 2 or 3 glioma, but molecularly as m-GBM. Cases with ring-like contrast enhancement and/or central necrosis at time of diagnostic surgery were excluded. Two dedicated neuropathologists blinded for clinical information independently revised the histological grade as defined in previous WHO classifications. Discordant cases were discussed to reach consensus. Patients were classified with a tailored NGS panel. We compared overall survival (OS) in this cohort with OS of a historical h-GBM cohort. RESULTS We identified 102 cases. Out of the 81 grade 2 gliomas (original diagnostics), upon pathology review 60 patients were still classified as grade 2 tumors, in 15 patients the grade was revised into grade 3, and in 6 patients into grade 4. Out of the 21 grade 3 patients, 11 were again classified as grade 3 after revisions. Five patients were revised as grade 2, and the other 5 as grade 4. Median age did not differ between groups (grade 2: 61yrs, grade 3: 58yrs, grade 4: 64yrs, h-GBM: 55 yrs). Clinical presentation of m-GBM was different compared to h-GBM. m-GBM more often presented with seizures than h-GBM (66% vs 27%) and more often with gliomatosis cerebri (35% vs 17%) reflected by a higher percentage of biopsies (78% vs 17%). We found no significant OS difference between histological grades in m-GBM and no difference with the historical h-GBM cohort. Median OS for grade 2 patients was 17 months versus 18 months in h-GBM patients. Additionally, we found no difference in OS between patients with an isolated TERTp mutation versus with EGFR amplification and/or 7+/10- in histological grade 2 patients (Median OS of 17 months versus 21 months respectively). CONCLUSION In our cohort of m-GBM with a low-grade histology and imaging characteristics of low-grade glioma, we observed a different clinical presentation compared to h-GBM. We did not see an impact of histological grade on OS in the context of m-GBM, and we did not see a longer survival for patients with an isolated TERTp mutation.