The “hook effect”: a case of multiple myeloma with a falsely low serum free light chain ratio – a case report

We discuss the case of a thirty-five-year-old female presenting with a significant acute kidney injury. As part of the diagnostic work-up, a non-invasive renal screen was sent, including tests for multiple myeloma (MM). Clinical suspicion of myeloma was low due to her age. She had a false-negative serum free light chain (sFLC) result due to antigen excess, a rare laboratory reporting error known as the "hook effect," leading to a delay in diagnosis. Her initial serum free lambda light chain result was 111.6 mg/L with a mildly low kappa:lambda ratio (0.12). The haematology team felt that the free light chain results were not high enough to explain the degree of kidney injury, and hence alternate diagnoses were considered. Due to persistent renal dysfunction a renal biopsy was performed, showing features in keeping with classic myeloma cast nephropathy. This prompted further dilutional studies on the original sFLC tests, which confirmed the spurious result, with a true lambda reading of 24,990 mg/L (24.9 g/L). A bone marrow biopsy followed, confirming the diagnosis of multiple myeloma. The hook effect occurs when extremely high concentrations of the substrate being measured lead to a false-negative result. This is a rare but well-documented phenomenon in immunoassay tests, such as tumor markers 1 . Antigen excess causing false negative results is also a known limitation in sFLC testing 2 however clinician knowledge of this is low. This highlights the need for Doctors to have awareness of test limitations, maintain a high degree of suspicion with incongruent results and consider repeating tests in appropriate clinical contexts. It also challenges the belief that MM only affects adults over fifty years old and encourages physicians to consider this diagnosis in certain patients.