The Diagnostic Yield of Cerebrospinal Fluid Analysis for the Diagnosis of Primary Central Nervous System Lymphoma: A Systematic Review

BACKGROUND: The gold standard for diagnosing primary central nervous system lymphoma (PCNSL) is brain biopsy, an invasive procedure with significant risks. The role of cerebrospinal fluid (CSF) examination, limited to cytology and flow cytometry in current practice, is acknowledged as a less invasive diagnostic method. We aimed to summarize available data concerning the efficacy and actual use of current standard CSF diagnostics in the diagnosis of PCNSL.

METHODS: A systematic review and meta-analysis of 144 studies (n = 9493 patients) was conducted, assessing detection rates of cytology and flow cytometry and the proportion of diagnoses based on CSF analysis. The QUADAS-2 tool was used to evaluate study quality and bias.

RESULTS: Meta-analysis showed an 18% pooled detection rate for positive CSF results, with 17% for cytology and 20% for flow cytometry. Only 8% of diagnoses were made using CSF analysis. Most studies had a high risk of bias.

CONCLUSIONS: Despite its established role in guidelines, CSF analysis remains underutilized for diagnosing PCNSL, with room to improve its clinical impact. Novel techniques, such as chemokines and circulating tumor DNA (cfDNA) analysis, hold promise to unlock the untapped potential of CSF diagnostics, offering significant advancements in non-invasive PCNSL diagnosis.