A patient with active renal cell carcinoma (RCC) with lung metastases treated with pembrolizumab and axitinib presented with new-onset seizures. MRI revealed ill-defined areas of T2 and FLAIR hyperintensity in the left periventricular and supratentorial regions with mild diffusion restriction, and subtle enhancement in the right frontal lobe. Immunotherapy was held and a course of pulse-dose steroids was initiated, followed by a prolonged steroid taper. A repeat MRI four weeks later revealed multiple contrast-enhancing lesions prompting a neuro-oncology evaluation. A biopsy was recommended, and it showed a grade 4 glioma.

This case demonstrates the diagnostic dilemma that immunotherapy-induced neuro-toxicities represent based on radiographic findings which can mimic both metastatic and primary brain tumors. Having a lower threshold for brain biopsy can help in ambiguous cases and can eliminate this diagnostic uncertainty and help with early and prompt management.