Case ReportDiagnostic Utility of Measuring Free Light Chains in the Cerebrospinal Fluid of Patients With Multiple Myeloma
Introduction
Although multiple myeloma (MM) is a bone marrow disorder, up to 20% of patients will ultimately develop extramedullary disease, and approximately 1% of MM patients develop central nervous system (CNS) MM.1, 2 Even with medical advances over the past decade, CNS MM carries a life expectancy of 4 to 6 months.3 The diagnosis and monitoring of CNS MM on cytology can be challenging, because of limited volumes sampled, the fragility of plasma cells ex vivo, and the often anaplastic appearance of plasma cells in cerebrospinal fluid (CSF) evaluated by nonhematopathologists. The utility of monitoring the free light chains (FLCs) secreted by malignant plasma cells in the CSF in patients with CNS MM is unknown.
Free light chains are secreted immunoglobulin light chains that are typically present at low levels in the serum.4 A commercially available nephelometric assay for FLCs has resulted in significant improvements in the diagnosis and monitoring of classic MM isolated to the marrow space. The FLC assay has also been reported to reliably detect intrathecal (IT) immunoglobulin production in CSF in disorders such as multiple sclerosis and CNS secretory B cell malignancies,5, 6, 7 and background levels of FLCs in the CSF of control subjects were found to be negligible.6, 8 Only a single retrospective study has reported measurements of FLCs in the CSF of 3 patients with known CNS MM using a commercially available serum assay.9 This study reports the levels of FLC measured in CSF of MM patients in whom there was concern for CNS MM.
This study was approved by the institutional review board of the Mount Sinai Hospital in accordance with federal regulations.
Section snippets
Case Reports
Herein we report data from 9 MM patients from whom CSF was obtained to evaluate cause of neurological symptoms that had raised clinical concern for CNS-MM. In Table 1 the basic clinical characteristics of the 9 patients are outlined. Samples were obtained from 9 sequential patients at our institution in whom there was a high suspicion of CNS MM between 2011 and 2013. Generally, these patients had either relapsed or refractory MM after many lines of therapy and the median age of initial MM
Discussion
Several recent clinical studies have validated the use of the serum FLC ratio in the diagnosis of MM and in monitoring of disease burden.10, 11, 12, 13 This assay has also been validated in CSF,5, 6, 7 however, the assay has never been used for the diagnosis of CNS MM. This is a rare and dire complication of MM, and the diagnosis is often difficult and dependent on either identification of anaplastic plasma cells on cytology or gross neuroimaging abnormalities, typically only evident in the
Conclusion
We present data from CSF taken from 9 MM patients in whom there was concern for CNS MM. The data from this small cohort support the use of measuring FLCs in CSF to diagnose CNS MM and to monitor response to therapy. Although the rarity of this manifestation of MM would limit the ability to validate FLC measurement as a sole test for CNS MM, this condition portends a bad outcome if not treated quickly, and these data suggest that incorporation of the FLC assay into a multifactorial diagnostic
Disclosure
The authors have stated that they have no conflicts of interest.
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2016, Clinical Lymphoma, Myeloma and LeukemiaCitation Excerpt :Extramedullary MM is often difficult to diagnose and carries a poor prognosis. Unlike the central nervous system, where the presence of FLCs alone is suggestive of extramedullary disease,8 the pleural space is not separated from the systemic circulation by a highly restrictive barrier. Exudative effusions are characterized by the presence of high protein and cellularity in pleural effusions.
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