Atypical CNS relapse in early-stage double-hit DLBCL: clinical implications for surveillance and prophylaxis.

Diffuse large B cell lymphoma (DLBCL) is a prevalent subtype of non-Hodgkins lymphoma and can occasionally present as a rare and aggressive testicular variant. This case presents a middle-aged male patient with stage IE testicular DLBCL who was successfully treated with DA-EPOCH-R chemotherapy and radiation, attaining a 5 year remission. He later developed neurological symptoms initially attributed to an acoustic neuroma but was ultimately diagnosed with isolated central nervous system (CNS) relapse of DLBCL. CNS recurrence remains a concern, despite prophylactic strategies. The patient was then treated with the MATRix regimen with close monitoring for transplant requirements. This case underscores the question of necessitating CNS prophylaxis in high-risk patients. We also highlight novel therapeutic strategies, and emerging molecular markers may hold promise in improving risk stratification and improving long-term outcomes for this patient population.