Case Report: Rare presentations of glioblastoma: three multifocal and one cerebellar cases highlighting the value of shared clinical experience.

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, typically presenting as a single supratentorial lesion. Multifocal/multicentric, and infratentorial variants are rare but clinically significant, often mimicking metastatic disease and limiting the feasibility of standard treatment. Their management remains challenging, and dedicated therapeutic guidelines are lacking. METHODS: We describe four uncommon GBM presentations, three multifocal supratentorial tumors and one cerebellar tumor, and integrate their clinical trajectories with a review of the literature to highlight diagnostic and therapeutic considerations. RESULTS: Across cases, diagnosis required comprehensive neuroimaging and, in several instances, exclusion of an extracranial primary malignancy. Molecular profiles were consistent with IDH-wildtype GBM. Treatment feasibility varied substantially: one patient was unable to receive tumor-directed therapy because of poor performance status, one discontinued treatment after severe hematologic toxicity, one younger patient with preserved performance status initiated standard chemoradiotherapy, and the cerebellar GBM patient was not eligible for adjuvant therapy because of postoperative deterioration and posterior fossa involvement. Survival was short in three cases, ranging from approximately 50 days to 7.5 months after diagnosis, and was approximately one month in the cerebellar case. CONCLUSION: Rare presentations of GBM, including multifocal and cerebellar disease, carry substantial diagnostic ambiguity, limited therapeutic options, and a markedly poor prognosis. Early multidisciplinary evaluation, optimized supportive care, and research focused on tailored treatment strategies are urgently needed to improve outcomes in these challenging GBM subtypes.