Central nervous system infection caused by Mycobacterium xenopi is exceptionally rare and may mimic intracranial neoplasia. A 60-year-old woman with poorly controlled diabetes presented with progressive headache and left homonymous hemianopia. Magnetic resonance imaging showed an irregularly enhancing right occipital mass-like lesion with marked edema and tumor-like magnetic resonance spectroscopy. Stereotactic biopsy demonstrated chronic granulomatous inflammation without neoplasia; periodic acid-Schiff, Gomori methenamine silver, and acid-fast stains were negative. Metagenomic next-generation sequencing of sterile, unfixed lesional brain tissue detected 2,347 species-specific reads assigned to M. xenopi, with a negative laboratory control. Targeted mycobacterial PCR performed during the diagnostic work-up on remaining biopsy-derived brain tissue was also reported positive for M. xenopi, providing concordant molecular support. Because tissue was limited, no separate specimen was submitted for culture or susceptibility testing. The patient received oral rifampicin, ethambutol, clarithromycin, and moxifloxacin. Headache resolved within 2 weeks, bedside visual-field assessment suggested partial improvement, and available records documented treatment for more than 6 months without clinically apparent adverse events. One-year non-contrast computed tomography showed right occipital encephalomalacic evolution without an obvious persistent mass-like lesion or mass effect. This case highlights the value of tissue-based molecular testing in tumor-mimicking central nervous system granulomas when conventional staining is nondiagnostic, while underscoring the continuing importance of culture, susceptibility testing, and prolonged objective follow-up.
