Diffuse hemispheric glioma, H3 G34-Mutant
General description
Diffuse hemispheric glioma, H3 G34-mutant represents a rare but aggressive pediatric-type diffuse high-grade glioma that primarily affects adolescents and young adults. The tumor occurs in less than 1% of all gliomas but accounts for up to 15% of high-grade gliomas in adolescents and young adults. The median age at diagnosis is consistently reported between 15-18 years, with a typical age range of 7-66 years, though the majority of patients (approximately 75-90%) are younger than 30 years.
These tumors are invariably IDH-wildtype and characterized by specific molecular alterations including frequent ATRX mutations (93-95%), TP53 mutations (87-88%), and MGMT promoter methylation (70-82%). The absence of Olig2 expression is a hallmark feature, occurring in 100% of cases. TERT promoter mutations are characteristically absent, which distinguishes these tumors from IDH-wildtype glioblastomas. The H3F3A G34R mutation predominates (94% of cases), with G34V mutations being relatively rare (6% of cases).
References
- Crowell, Cameron, et al. "Systematic review of diffuse hemispheric glioma, H3 G34-mutant: Outcomes and associated clinical factors." Neuro-Oncology Advances 4.1 (2022): vdac133.
- Le Rhun, Emilie, et al. "The clinical and molecular landscape of diffuse hemispheric glioma, H3 G34-mutant." Neuro-Oncology (2025): noaf015.
- Shao, Hanbing, et al. "MRI characteristics of H3 G34–mutant diffuse hemispheric gliomas and possible differentiation from IDH–wild-type glioblastomas in adolescents and young adults." Journal of Neurosurgery: Pediatrics 33.3 (2023): 236-244.
- Kurokawa, Ryo, et al. "Neuroimaging features of diffuse hemispheric glioma, H3 G34‐mutant: A case series and systematic review." Journal of Neuroimaging 32.1 (2022): 17-27.
Cerebral mass
Diffuse hemispheric glioma, H3 G34-mutant demonstrate hemispheric localization, primarily affecting the frontal and parietal lobes, with involving two or more brain lobes, reflecting their strong local dissemination ability.
The tumors typically present as cortico-subcortical lesions, with poorly defined margins in 63% of cases and well-defined margins in 36%. A notable feature is the frequent contact with specific anatomical structures, with leptomeningeal contact observed in 92.3% of cases and ependymal extension present in 53-87.5% of patients.
The tumors typically appear iso- to hypointense on T1-weighted imaging and mildly hyperintense or hyperintense on T2-weighted and FLAIR sequences, with profound diffusion restriction. A characteristic and diagnostically significant feature is the frequent absence or faintness of contrast enhancement.
Cystic or necrotic changes are observed in 74% of cases on MRI, while intratumoral hemorrhage occurs in approximately 30% of patients. Calcification has been reported in 20% of cases, with intratumoral calcification evident in a subset of cases.