Insights from two cases of granular cell astrocytoma as an uncommon histological variant of high-grade glioma

Granular cell astrocytoma (GCA) is a rare, aggressive variant of infiltrating glioma, often misdiagnosed due to its morphologic overlap with non-neoplastic and histiocytic lesions. We report two unique cases of GCA in middle-aged adults, presenting with headache, gait instability and hemiparesis. Radioimaging analysis revealed bilateral thalamic and corpus callosal lesions, suggesting high-grade gliomas. Histopathological evaluation revealed granular cell tumors after immune and molecular profiling of the tumor. MIB-1 Proliferative Index was variable. Molecular profiling demonstrated IDH1 R132H wild-type and ATRX lost expressions in both cases. Being mid-line in location, Case 2 was also evaluated for H3K27M, which was non-mutant along with retained H3k27Me3 expression. GCA shares features with IDH-wildtype glioblastoma, indicating aggressive behavior despite its deceptively low-grade histology. Accurate diagnosis relies on the integration of histologic and molecular evaluation. This case highlights the need for awareness of GCA’s distinct profile and potential avenues for future research into targeted therapies for this rare entity.