Introduction Serum free light chain assay (FLC) is a valuable tool in diagnosing multiple myeloma. The prozone phenomenon, or hook effect, occurs with exceptionally high antigen levels, leading to underestimated FLC levels and false negatives. (2). FLC levels are routinely used for confirming multiple myeloma suspicions. This is a case of newly diagnosed multiple myeloma (MM) that exhibited the prozone effect on the FLC assay, delaying diagnosis. 

Case A 62-year-old woman presented to the emergency department after her outpatient lab work showed evidence of renal failure. Her symptoms included fatigue, shortness of breath, pallor and back pain. Labs revealed BUN 118 mg/dL, creatinine 11.9 mg/dL, hemoglobin 7 g/dl, calcium 10 mg/dL, and profound hypogammaglobulinemia. Computed tomography of the chest abdomen and pelvis showed small lytic lesions in the posterior aspect of T10-11. The patient was admitted for acute renal failure secondary to suspected multiple myeloma. Serum protein electrophoresis revealed M spike in the gamma globulin region. Initial FLC showed low levels of kappa light chain free serum <0.6 mg/L with high kappa/lambda ratio. Bone marrow biopsy demonstrated a hypercellular marrow (80% plasma cells), with FISH studies showing 4:14 translocation. Repeat FLC with dilution showed kappa light chain of 18403.8 mg/L and a kappa/lamda ratio of > 1000.00. Beta 2 microglobulin was found to be elevated at 36.89 mg/L, significant proteinuria with Bence-Jones protein was noted, and lytic foci were found in the calvarium, bilateral humeral shafts, and bilateral radial shafts on osseous survey. Initial therapeutic regimen consisted of cyclophosphamide, bortezomib, dexamethasone and daratumumab. Cyclophosphamide and dexamethasone were stopped due to intolerable side effects. Repeat kappa free light chains measured at 40 mg/L and ratio at 2.0. The patient remains dialysis dependent and ultimate plan is for autologous bone marrow transplant.  

Discussion The prozone effect, a rare lab phenomenon, occurs when high FLC levels interrupt complex formation, leading to underestimated antigen levels. (2). In FLC assays, multivalent proteins act as linkers, but very high FLC levels saturate binding sites, paradoxically decreasing fully formed complexes. (4). This effect can be overcome by dilution of the sample.  In the above case, the initial findings of FLC were variable, notable for an elevated kappa/lambda ratio and decreased kappa light chains. After dilution high levels of FLC resulted. This confirms that the low levels initially noted were a result of the Prozone effect. Timely recognition of the prozone effect ensures accurate diagnosis, prevents delays in therapy thus reducing disease morbidity.