Cerebrospinal fluid interleukin-10 is a potentially useful biomarker in immunocompetent primary central nervous system lymphoma (PCNSL)

Abstract

The diagnosis of primary central nervous system lymphoma (PCNSL) by radiographical examination is often difficult because of its similarity to other brain tumors. To test whether interleukin-10 (IL-10) and IL-6 can be used to distinguish PCNSL from other brain tumors that are radiographically similar, cerebrospinal fluid (CSF) levels of IL-10 and IL-6 were measured in 66 patients with intracranial tumors (PCNSLs: 26 cases; other brain tumors: 40 cases). In the patients with PCNSLs, the median CSF levels of IL-10 and IL-6 were 27 pg/mL and 5.4 pg/mL, respectively. The CSF IL-10 and IL-6 levels were significantly higher in PCNSLs than in the other brain tumors. To validate the diagnostic value of CSF IL-10 in PCNSL, we prospectively examined 24 patients with brain lesions that were suspected to be PCNSL. We observed that the CSF IL-10 levels were significantly higher in PCNSLs than in other brain tumors. At an IL-10 cutoff level of 9.5 pg/mL, the sensitivity and specificity were 71.0% and 100%, respectively. After therapy, the CSF IL-10 levels were decreased in all patients and were increased at relapse in most of these patients. Immunohistochemically, all PCNSLs, except for 1 unclassified PCNSL, expressed both IL-10 and IL-10 receptor-A. In the patients with high CSF IL-10, IL-10 expression levels in tumor were relatively higher, compared with low CSF IL-10; however, there was no significant difference between these groups. In addition, elevated CSF level of IL-10 was significantly associated with having a shorter progression-free survival (hazard ratio, 3.37; 95% confidence interval, 0.985-11.528; log-rank, P= .038). These results indicate that the CSF level of IL-10 may be a useful diagnostic and prognostic biomarker in patients with PCNSLs.

The diagnostic role and dynamic changes in cerebrospinal fluid neopterin during treatment of patients with primary central nervous system lymphoma

“…MRI does not have a high specificity for distinguishing PCNSL from glioma and metastatic brain tumors39, 40 and often results in misdiagnosis 6, 8, 9. In the present study, the sensitivity of MRI for the diagnosis of PCNSL was 52.4% (11/21), whereas the sensitivity of CSF Npt concentration for the diagnosis of PCNSL was 90% (9/10) in the 10 false‐negative PCNSL cases.…”

“…Magnetic resonance imaging (MRI), especially contrast‐enhanced MRI, is the method of choice for the detection of PCNSL. However, as PCNSL does not have a characteristic radiological feature, misdiagnosis is not uncommon,6, 8, 9 and the differential diagnosis of PCNSL from other brain tumors such as meningioma, glioma, and metastatic brain tumors and some inflammatory diseases such as sarcoidosis and multiple sclerosis is typically challenging 8. Indeed, correct diagnosis of an atypical focal brain lesion based solely on radiological examination is a formidable challenge.…”

CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma

“…These results are consistent with previous observations regarding the relationship between elevated IL-10 levels and adverse outcome in DLBCL. 14,29 Moreover, serial analysis demonstrated that CSF IL-10 concentration within the lumbar sac and in the brain ventricle reproducibly correlated with clinical course, both at diagnosis and in PCNSL and SCNSL patients at relapse. CSF levels of IL-10 also correlated with clinical response or progression in CNS lymphoma patients who participated in a phase 1 trial of intraventricular rituximab plus methotrexate.…”

“…13 Candidate peptides hypothesized to have a role in the pathogenesis of CNS lymphomas have also been evaluated in preliminary studies, including interleukin (IL)-10, also identified using proteomic methods, 13 and the CXC chemokine ligand (CXCL)13, a mediator of B-cell migration. Recently, Sasayama et al 14 found elevated IL-10 in CSF specimens from 31 immunocompetent patients with PCNSL compared with 59 patients with other types of brain tumors, mainly malignant gliomas. Fischer et al 15 detected elevated CXCL13 concentration in CSF from 30 lymphoma patients relative to 40 control subjects.…”

Interleukin 10 Level in the Cerebrospinal Fluid as a Possible Biomarker for Lymphomatosis Cerebri

“…In patients with intracranial tumors, the levels of IL-10 in the CSF have been found to be significantly higher in those with PCNSLs than in those with other brain tumors (9). However, the utility of the IL-10 levels in CSF for identifying LC has not been clarified.…”