Intrathecal IgM synthesis as a diagnostic marker in patients with suspected CNS lymphoma

• Published in: Journal of neurochemistry Vol. 168; no. 6; pp. 1157 - 1167
• Main Authors: Reinecke, Raphael, Jahnke, Kolja, Foltyn‐Dumitru, Martha, Lachner, Karsten, Armbrust, Moritz, Weber, Katharina J., Zeiner, Pia S., Czabanka, Marcus, Brunnberg, Uta, Hartmann, Sylvia, Steinbach, Joachim P., Ronellenfitsch, Michael W.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.06.2024
• Subjects: Adult; Aged; Aged, 80 and over; biomarker; Biomarkers, Tumor - cerebrospinal fluid; Biopsy; Central Nervous System Neoplasms - cerebrospinal fluid; Central Nervous System Neoplasms - diagnosis; Central Nervous System Neoplasms - immunology; Cerebrospinal fluid; CNS lymphoma; Diagnosis; Diagnostic systems; Differential diagnosis; Female; Humans; Immunoglobulin M; Immunoglobulin M - cerebrospinal fluid; immunoglobulin synthesis; Lymphoma; Lymphoma - cerebrospinal fluid; Lymphoma - diagnosis; Magnetic Resonance Imaging; Male; Middle Aged; Neurological diseases; Retrospective Studies; Sensitivity and Specificity; Synthesis; Young Adult; biomarker; CNS lymphoma; immunoglobulin synthesis
• ISSN: 0022-3042; 1471-4159; 1471-4159
• DOI: 10.1111/jnc.16069

For CNS lymphomas (CNSL), there is a high need for minimally invasive and easily obtainable diagnostic markers. Intrathecal IgM synthesis can easily be determined in routine CSF diagnostics. The aim of this study was to systematically investigate the diagnostic potential of intrathecal IgM synthesis in primary and secondary CNSL (PCNSL and SCNSL). In this retrospective study, patients with a biopsy‐proven diagnosis of PCNSL or SCNSL were compared with patients with other neurological diseases in whom CNSL was initially the primary radiological differential diagnosis based on MRI. Sensitivity and specificity of intrathecal IgM synthesis were calculated using receiver operating characteristic curves. Seventy patients with CNSL were included (49 PCNSL and 21 SCNSL) and compared to 70 control patients. The sensitivity and specificity for the diagnosis of CNSL were 49% and 87%, respectively, for the entire patient population and 66% and 91% after selection for cases with tumor access to the CSF system and isolated intrathecal IgM synthesis. In cases with MRI‐based radiological suspicion of CNSL, intrathecal IgM synthesis has good specificity but limited sensitivity. Because of its low‐threshold availability, analysis of intrathecal IgM synthesis has the potential to lead to higher diagnostic accuracy, especially in resource‐limited settings, and deserves further study. We suggest intrathecal IgM synthesis as a novel and easily accessible biomarker in patients with suspected central nervous system lymphoma. Our systematic study of the biomarker revealed high specificity but limited sensitivity in patients with CNS lymphoma when compared to control groups of other neurological diseases with similar radiological patterns. Because of its low threshold availability, intrathecal IgM synthesis analysis has the potential to improve diagnostic accuracy for CNS lymphoma, particularly in resource‐limited settings.