Diagnostic Pathways and Procedural Risk in Primary Central Nervous System Lymphoma: A Nationwide Analysis

Introduction: Primary central nervous system lymphoma (PCNSL) is an aggressive malignancy in which timely diagnosis is critical. While neurosurgical biopsy remains the gold standard, cerebrospinal fluid (CSF)-based diagnostics are frequently deployed. Owing to the rarity of this condition, little is known about clinical characteristics, test utilization, social determinants of health, and complication rates in the context of securing a PCNSL diagnosis. We evaluated approaches for diagnosing PCNSL, post-procedural complications, and clinical and socioeconomic associations with adverse events. Methods: We queried the PearlDiver Mariner claims database to identify adults with newly diagnosed PCNSL between 2011 and 2023. CPT and ICD codes were used to identify lumbar puncture (LP) and/or neurosurgical biopsy performed before diagnosis. Patients were stratified by diagnostic pathway: LP-only, Biopsy-only, or both LP and biopsy. We used logistic regression to identify predictors of adverse events. Results Among 2,549 total patients, 1957 (76.8%), 398 (15.6%), and 194 (7.6%) comprised the LP-only, Biopsy-only, or both LP and biopsy pathways, respectively. LP-only patients were younger, more frequently male, Medicaid-insured, and economically disadvantaged (P< 0.001 for each). Rates of post-procedural thromboembolic complications were 5.4%, 10.1%, and 6.7% for LP-only, Biopsy-only, and both LP and biopsy, respectively (P<0.002). Biopsy-only was associated with increased odds of procedural complications (OR 3.21, 95% CI 1.79-5.69, P<0.001), thromboembolic events (OR 1.85, 95% CI 1.39-2.45, P<0.001), and medical complications (OR 1.87, 95% CI 1.49-2.33, P<0.001) compared to LP alone. Conclusions: The choice of diagnostic modalities utilized to secure a diagnosis of PCNSL may be influenced by patient-level clinical and socioeconomic factors. PCNSL patients may represent a uniquely high-risk subgroup for neurosurgical biopsy, emphasizing the importance of advancing CSF-based diagnostics.