Infant-Type Hemispheric Gliomas: A Review of Clinical, Radiologic, Histopathologic, and Molecular Features

Infant-type hemispheric gliomas (IHGs) are extremely rare, large, hemorrhagic tumors of the cerebral hemispheres commonly diagnosed during infancy. Treatment of IHG has been adapted from historical clinical trials that enrolled infants with high-grade glioma (HGG) and involves maximal safe surgical resection followed by adjuvant chemotherapy. With this treatment, IHGs have shown good overall survival rates in retrospective studies; however, survivors have poor long-term neurologic and neurocognitive outcomes because the clinical course is fraught with high rates of surgical morbidity, acute intracranial hemorrhage, tumor progression, and use of multiple chemotherapy regimen for treatment. At the molecular level, IHGs are uniquely driven by RTK fusions, and their DNA methylation profiles distinguish them from other pediatric-type diffuse HGGs while clustering more closely with low-grade desmoplastic infantile ganglioglioma/astrocytoma. Although RTK fusions render IHGs targetable by tyrosine kinase inhibitors (TKIs), their optimal role in infants is yet to be determined. Consequently, TKIs are most often used in the recurrent setting, while surgery and chemotherapy continue to represent the standard primary treatment approach. This review summarizes historical clinical trials, delineates the histopathologic and molecular landscape of IHG, and highlights current therapeutic gaps, underscoring the need for collaborative research efforts to establish standardized treatment approaches.