Clinical utility of repeat brain biopsy in recurrent or refractory primary CNS lymphoma – a diagnostic dilemma

Purpose: Despite advances in therapy and improved survival for patients with primary central nervous system lymphoma (PCNSL), optimal management of suspected recurrent or refractory PCNSL (r/r PCNSL) remains unclear. Repeat brain biopsy is often performed to confirm recurrence, though its diagnostic and therapeutic utility is uncertain. This study evaluates whether repeat biopsy provides new insights that influence treatment. Methods: A retrospective analysis was conducted on patients with confirmed PCNSL who underwent repeat biopsy for suspected r/r PCNSL between 2005 and 2023. Patients with other CNS neoplasms, demyelinating disorders, or active systemic disease were excluded. Data analysis used R version 4.4. Results: Twenty patients met the inclusion criteria (55% female). Median age was 59 years at diagnosis and 62 years at repeat biopsy. Presenting symptoms were not significantly different (p = 0.2), though gait instability, weakness, and cognitive decline were more frequent in r/r PCNSL. Initial PCNSL often presented with single lesions, while r/r PCNSL showed multiple lesions (p < 0.05). Periventricular enhancement was significantly more frequent in r/r PCNSL (p < 0.05), while other radiologic features were comparable. Repeat biopsy confirmed diffuse large B cell lymphoma (DLBCL) in 90% of cases; nonspecific gliosis and radiation necrosis were identified in two patients. No infections or alternate malignancies were found. Post-biopsy, chemotherapy regimens were altered in 50% of cases, though survival outcomes did not differ (p = 0.79). Conclusions: Repeat biopsy most often reaffirmed the original diagnosis of DLBCL. Although results prompted treatment adjustments, these changes did not improve overall survival.