Serum Free Light Chains in Lymphoma: A Phenotype-First Framework for Biological Interpretation, Analytical Control, and Clinical Use

Serum free light chains (sFLC) reflect immunoglobulin production and renal clearance, making abnormal results biologically heterogeneous in lymphoma. We reviewed clinical, translational, and analytical evidence using a documented PubMed search. Three operational patterns should be distinguished: monoclonal-pattern elevation, polyclonal-pattern elevation, and ratio-only abnormality. The kappa-plus-lambda concentration is an overlapping measure of total circulating burden rather than a fourth exclusive phenotype. In diffuse large B-cell lymphoma, some cohorts reported International Prognostic Index-adjusted associations and improved model discrimination, whereas other studies did not confirm independent prognostic value. Evidence in classical Hodgkin lymphoma and chronic lymphocytic leukemia also depends on endpoint, adjustment, and treatment setting. Prediagnostic associations in human immunodeficiency virus infection, transplantation, and population cohorts do not establish screening utility. In Waldenström macroglobulinemia, involved-chain kinetics may supplement established assessment in selected patients, although clinical benefit from sFLC-directed management has not been demonstrated. Historical treatment regimens, overlapping cohorts, inconsistent renal adjustment, assay differences, and limited external validation restrict transferability. The proposed framework integrates phenotype, renal function, assay, sampling time, and disease context. It is an interpretive proposal, not a validated prognostic score or treatment algorithm.