Characteristics of diffuse hemispheric gliomas, H3 G34-mutant in adults

Abstract

Background Diffuse hemispheric gliomas, H3 G34-mutant (DHG H3G34-mutant) constitute a distinct type of aggressive brain tumors. Although initially described in children, they can also affect adults. The aims were to describe the characteristics of DHG H3G34-mutant in adults and to compare them to those of established types of adult WHO grade IV gliomas. Methods The characteristics of 17 adult DHG H3G34-mutant, 32 H3.3 K27M-mutant diffuse midline gliomas (DMG), 100 IDH-wildtype and 36 IDH-mutant glioblastomas were retrospectively analyzed. Results Median age at diagnosis in adult DHG H3G34-mutant was 25 years (range: 19-33). All tumors were hemispheric. For 9 patients (56%), absent or faint contrast enhancement initially suggested another diagnosis than a high-grade glioma, and diffusion-weighted imaging seemed retrospectively more helpful to suspect an aggressive tumor than MR-spectroscopy and perfusion MRI. All cases were IDH-wildtype. Most cases were immunonegative for ATRX (93%) and Olig2 (100%) and exhibited MGMT promoter methylation (82%). The clinical and radiological presentations of adult DHG H3G34-mutant were different from those of established types of adult grade IV gliomas. Median overall survival of adult DHG H3G34-mutant was 12.4 months compared to 19.6 months (p=.56), 11.7 months (p=.45) and 50.5 months (p=0.006) in H3.3 K27M-mutant DMG, IDH-wildtype and IDH-mutant glioblastomas, respectively. Conclusions Adult DHG H3G34-mutant are associated with distinct characteristics compared to those of established types of adult WHO grade IV gliomas. The present study supports considering these tumors as a new type of WHO grade IV glioma in future classifications.

The prognostic significance of further genotyping H3G34 diffuse hemispheric gliomas

“…Subsequently, 6 studies were further excluded because of missing individual participant data or duplicated populations. Finally, we included 20 studies with 257 H3G34-mutant DHGs for integrated analyses 3,6,7,10,11,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] (Fig. 1).…”

“…These publications primarily reveal concomitant genetic events and the overall prognosis and progression of H3G34-mutant DHGs. 7,11,19,22,23,26,[31][32][33] However, it is still unclear whether these tumors have similar outcomes or if they can be further segregated into different prognostic subgroups. Our study demonstrated several genetic markers that are of clinical importance.…”

“…In the brain, H3G34‐mutated DHGs are uncommon, with a developing literature that describes their natural history. These publications primarily reveal concomitant genetic events and the overall prognosis and progression of H3G34‐mutant DHGs 7,11,19,22,23,26,31‐33 . However, it is still unclear whether these tumors have similar outcomes or if they can be further segregated into different prognostic subgroups.…”

Neuroimaging features of diffuse hemispheric glioma, H3 G34‐mutant: A case series and systematic review

“…A total of 332 abstracts were screened, of which 53 potentially eligible articles were selected for further review. After excluding 41 articles and including one article extracted from the citation review of each relevant article (no case with pathologically proven DHG‐G34m, 25 articles; no radiological findings or images, 14 articles; and insufficient patient‐specific information, 2 articles), 12 articles met the selection criteria for the systematic review 1,6–16 . The year of publication of the selected articles ranged from 2017 to 2021.…”

“…After excluding 41 articles and including one article extracted from the citation review of each relevant article (no case with pathologically proven DHG-G34m, 25 articles; no radiological findings or images, 14 articles; and insufficient patient-specific information, 2 articles), 12 articles met the selection criteria for the systematic review. 1,[6][7][8][9][10][11][12][13][14][15][16] The year of publication of the selected articles ranged from 2017 to 2021. With the additional three cases from our hospital, the final study cohort included 59 cases of DHG-G34m.…”