Abstract
BACKGROUND: Glioblastoma multiforme (GBM), a high-grade primary brain tumor, presents a formidable challenge in neuro-oncology because of its aggressive nature, infiltrative growth, and limited response to treatment. The septum pellucidum represents an uncommon and unexpected location for GBM, adding complexity to the diagnosis and management of this rare intracranial malignancy. OBSERVATIONS: A 69-year-old male with a previous history of prostate carcinoma presented to an outside hospital with a 2-week history of a "trance-like state" and cognitive decline. Initial head computed tomography showed prominent ventricles without distinct mass lesions. Upon admission, magnetic resonance imaging demonstrated a mass within the inferior septum pellucidum extending to the third and both lateral ventricles. Biopsy findings indicated a GBM, World Health Organization central nervous system tumor grade 4, with immunopositivity for glial fibrillary acidic protein and a Ki-67 labeling index of 60%-70%. LESSONS: Identifying only 5 cases in more than 60 years of literature, this systematic review illustrates the diverse clinical presentations, diagnostic advancements, and management approaches for septum pellucidum GBM. https://thejns.org/doi/10.3171/CASE23770.