A 63-year-old male whose primary central nervous system (CNS) lymphoma has been in complete remission for 2 years presents to his oncologist for routine follow-up. The patient was previously treated with a course of methotrexate-based chemotherapy. His medical history is otherwise unremarkable. However, the patient is now experiencing persistent headache that does not resolve with use of nonsteroidal anti-inflammatory drugs and what he describes as "general clumsiness and brain fog" for the past 2 months. Further questioning and physical exam reveal visual field defects, as he commonly bumps into things and knocks things over because he does not see them. He has also had difficulty reading. Additionally, the patient shows evidence of gait ataxia; his gait is staggered, and his movements are uncoordinated. He also reports episodes of altered mental state where he cannot recall where he is or how to complete simple tasks that were not problematic in the past.

MRI reveals multiple brain lesions, which are confirmed by FDG-PET scan. Biopsy is performed, and histologic examination reveals several mutations: CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53, and JAK3. Cerebrospinal fluid analysis is also performed and is positive for interleukin-10 expression.