Abstract
Tumor biopsy is essential for the definitive diagnosis of central nervous system (CNS) lymphoma. However, the biopsy procedure carries the risk of complications such as bleeding, convulsions, and infection. Cerebrospinal fluid (CSF) β2‐microglobulin (β2‐MG), soluble IL‐2 receptor (sIL‐2R), and interleukin‐10 (IL‐10) are known to be useful diagnostic biomarkers for CNS lymphoma. The C‐X‐C motif chemokine ligand 13 (CXCL13) was recently reported to be another useful biomarker for CNS lymphoma. The purpose of this study is to establish a diagnostic algorithm that can avoid biopsy by combining these diagnostic biomarkers. In the first, we conducted a case‐control study (n = 248) demonstrating that the CSF CXCL13 concentration was significantly increased in CNS lymphoma patients compared with various other brain diseases (AUC = 0.981). We established a multi‐marker diagnostic model using CSF CXCL13, IL‐10, β2‐MG, and sIL‐2R from the results of the case‐control study and then applied the model to a prospective study (n = 104) to evaluate its utility. The multi‐marker diagnostic algorithms had excellent diagnostic performance: the sensitivity, specificity, positive predictive value, and negative predictive value were 97%, 97%, 94%, and 99%, respectively. In addition, CSF CXCL13 was a prognostic biomarker for CNS lymphoma patients. Our study suggests that multi‐marker algorithms are important diagnostic tools for patients with CNS lymphoma.
Highlights
Our study suggests that the Cerebrospinal fluid (CSF) multi-marker prediction algorithm can help diagnose central nervous system (CNS) lymphoma with surgical difficulties and be used for treatment planning
C-X-C chemokine receptor type 5 (CXCR5), a receptor of C-X-C motif chemokine ligand 13 (CXCL13), was highly expressed in the CNS lymphomas (Figure 1D). These results indicate that the CXCL13/CXCR5 signaling pathway may be activated in CNS lymphoma cells
Two patients had reelevation of CSF CXCL13 levels at the time of relapse, and after the therapy, the CSF CXCL13 levels were decreased again (Figure 3B). These results indicated that CSF CXCL13 is a useful disease monitoring marker for CNS lymphoma
Summary
Clinical and radiological characteristics alone make it difficult to diagnose CNS lymphoma. CXCL13 levels were increased in bronchoalveolar lavage fluid in non-small cell lung cancer, and high CXCL13 was reported to be a poor prognostic factor.[39]. Since some diseases have high CSF CXCL13 concentrations, diagnosis with a multi-marker is necessary. Rubenstein et al previously reported on the usefulness of CNS lymphoma diagnosis with the combination of FIGURE 3 A, Comparison of the serum or cerebrospinal fluid (CSF) levels of CXCL13 between CNS lymphoma and the other CNS diseases. CNS lymphoma patients with high CSF CXCL13 levels had poorer OS and PFS. CSF CXCL13 is a useful diagnostic biomarker for patients with CNS lymphomas. The CSF CXCL13 level is a useful prognostic factor for patients with CNS lymphoma. When the diagnostic value of these combinations of CSF markers is confirmed, risk of biopsy could be avoided and treatment can be started earlier for patients with CNS lymphoma
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