In the mid-19th century, Henry Bence Jones described the presence of free light chains (FLCs) in urine (1). A century later, work by Korngold and Lipari(2) characterized Bence Jones proteins and showed that they reacted with those found in myeloma. Although rarely appreciated, the designation of κ and λ for the 2 forms of Bence Jones proteins has remained standard nomenclature in tribute to those investigators. Nearly another half-century passed before immunoassays were developed to identify serum FLCs and begin to define their role(3).
Coincident with the development of serum FLC assays have been major improvements in the treatment of myeloma. Patients now have therapeutic options that include combinations of corticosteroids, thalidomide, lenalidomide, bortezomib, and stem cell transplant, along with newer investigational agents; thus, the prognosis for patients with myeloma continues to improve. The consequence of heightened awareness, a cavalcade of therapy, and prolonged survival have led to increased laboratory monitoring, reflected in the explosion of investigations using serum FLCs.
Yet, as with many such advances, cautionary tales arise. In the case presented here, a patient with myeloma was followed for 4 months without symptoms, and apparently comforted by the presence of a low concentration of κ serum FLCs. As her disease burden worsened, traditional laboratory test results, including hemoglobin, serum calcium, and urinary M-protein, indicated advancing myeloma, and treatment was begun. Although the patient improved, the serum FLCs markedly increased. This contradiction was resolved when previously stored samples were retested at a higher dilution, indicating that large antigen excess led to an artificially low result. The authors noted that this occurred in approximately 0.1% of samples, although it would be difficult to predict who might be at risk for this finding and whether earlier identification would have ultimately changed the outcome. As highlighted in this case, discordant results need to be further investigated, and there is no substitution for careful clinical observation.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors’ Disclosures of Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
- © 2010 The American Association for Clinical Chemistry