CXCL13 and IL-10 are highly specific for the diagnosis of PCNSL. (A-B) MRI features of PCNSL in 2 patients at diagnosis. (A) MRI depicts a homogeneously contrast-enhancing mass with vasogenic edema. At the time of diagnosis established by brain biopsy, the CSF contained CXCL13 concentration of 170 pg/mL and IL-10 concentration of 61 pg/mL. (B) Normal-appearing MRI of a patient with progressive neurologic symptoms who was aggressively treated with steroids before a diagnosis could be elicited. Four CSF collections and 1 brain biopsy were unrevealing, and the diagnosis of disseminated PCNSL was made at autopsy. The CSF collected and stored from this patient was later determined to contain CXCL13 concentration of 6236 pg/mL and IL-10 concentration of 76 pg/mL. (C) ROC analysis demonstrated that high concentrations of CXCL13 and IL-10 are each highly sensitive and specific for CNS lymphomas. A CSF concentration of CXCL13 >116 pg/mL is 71% sensitive and 94.9% specific for PCNSL (area under the curve [AUC], 0.841; 95% confidence interval [CI], 0.779-0.892). A CSF concentration of IL-10 >23 pg/mL is 63.9% sensitive and 94.1% specific for CNS involvement of lymphoma (AUC, 0.851; 95% CI, 0.789-0.901). Bivariate elevation of both CXCL13 plus IL-10 in CSF was 50% sensitive and 99.3% specific for CNS lymphoma (AUC, 0.746; 95% CI, 0.675-0.809). Elevation of either CXCL13 or IL-10 in CSF was 84.2% sensitive and 90.5% specific for the diagnosis of PCNSL (AUC, 0.874; 95% CI, 0.815-0.919). By contrast, the AUC of CSF albumin was 0.604 and significantly lower than CXCL13 or IL-10 (P < .0001).