Diagnostic Approach to Elevated Serum Free Light Chains
Initial Evaluation
- The National Comprehensive Cancer Network recommends performing serum immunofixation electrophoresis (SIFE) and urine immunofixation electrophoresis (UIFE) immediately, as these are more sensitive than standard electrophoresis and may detect monoclonal proteins missed by SPEP/UPEP 1, 2, 3
- Order SIFE and UIFE to identify small monoclonal proteins that may not produce visible spikes on standard electrophoresis 1, 2, 3
Risk Stratification
- A markedly abnormal FLC ratio (kappa/lambda >100 or <0.01) suggests a plasma cell disorder and warrants urgent bone marrow biopsy regardless of immunofixation results 3
- A moderately abnormal ratio (>3.1 or <0.26) with normal renal function is highly suggestive of a plasma cell disorder and warrants bone marrow evaluation 3
Comprehensive Hematologic Workup
- Bone marrow aspiration and biopsy with immunohistochemistry and/or flow cytometry should be performed to quantify clonal plasma cells and assess for light chain-only myeloma or AL amyloidosis 1, 2, 3
- Cytogenetic studies including FISH analysis should be performed for del(13), t(4;14), t(14;16), del(17p), and 1q21 amplification to assess risk stratification 2, 3
Imaging and End-Organ Assessment
- A skeletal survey (whole body low-dose CT or MRI preferred over plain radiographs) should be performed to detect lytic lesions 2, 3
- Cardiac evaluation should be considered if clinical suspicion for AL amyloidosis exists (unexplained heart failure, LV wall thickness ≥14mm, low voltage ECG) 4, 5