What is the diagnosis and treatment for a patient with elevated kappa light chain, abnormal kappa/lambda ratio, joint stiffness, bone pain, and hip pain?

Diagnostic Evaluation and Management of Suspected Light Chain Multiple Myeloma

This patient requires immediate comprehensive workup for light chain multiple myeloma given the elevated kappa light chain (25.84 mg/dL) with borderline abnormal kappa/lambda ratio (1.21, upper limit of normal 1.65) combined with classic myeloma symptoms of bone pain, joint stiffness, and hip pain. 1, 2

Immediate Diagnostic Workup Required

The following tests must be obtained urgently to establish or exclude multiple myeloma:

• Serum protein electrophoresis (SPEP) with immunofixation electrophoresis (IFE) - essential for detecting monoclonal proteins, though may be negative in light chain-only disease 3, 1
• 24-hour urine collection with urine protein electrophoresis and immunofixation - critical as light chain myeloma often presents with urinary M-protein that may be missed on serum testing alone 1, 4
• Bone marrow aspiration and biopsy - required to assess plasma cell percentage (≥10% clonal plasma cells needed for myeloma diagnosis) and perform cytogenetic/FISH studies 3, 1
• Complete skeletal survey including spine, pelvis, skull, humeri, and femurs to evaluate for lytic bone lesions, which would fulfill CRAB criteria 3
• Laboratory panel: complete blood count, serum creatinine, calcium, albumin, LDH, and beta-2 microglobulin 3, 1

Interpretation of Current Light Chain Results

Your patient's kappa/lambda ratio of 1.21 sits at the upper boundary of normal (0.26-1.65), which creates diagnostic ambiguity: 1, 2

• A ratio >1.65 would definitively indicate monoclonal kappa disease requiring immediate hematologic evaluation 1, 2
• The borderline ratio combined with elevated absolute kappa level (25.84 mg/dL) and classic myeloma symptoms (bone pain, joint stiffness) strongly suggests evolving light chain myeloma rather than benign polyclonal elevation 1, 5
• Renal function must be assessed immediately, as chronic kidney disease can elevate both light chains and expand the "normal" ratio range to 0.34-3.10, potentially masking monoclonal disease 1, 2

Diagnostic Criteria for Multiple Myeloma

To diagnose symptomatic multiple myeloma, the patient must meet both criteria: 3

1. ≥10% clonal plasma cells on bone marrow examination or biopsy-proven plasmacytoma
2. Evidence of end-organ damage (CRAB criteria) attributable to the plasma cell disorder:
   • Calcium elevation (>11 mg/dL)
   • Renal insufficiency (creatinine >2 mg/dL or creatinine clearance <40 mL/min)
   • Anemia (hemoglobin <10 g/dL or >2 g/dL below normal)
   • Bone lesions (lytic lesions on skeletal survey, CT, or PET-CT)

Your patient's bone pain and hip pain suggest possible lytic bone lesions, which would fulfill the "B" criterion if confirmed on imaging. 3

Common Diagnostic Pitfalls

• Light chain-only myeloma (15-20% of cases) produces no M-spike on serum protein electrophoresis, making it easily missed if only SPEP is performed without free light chain testing 5, 6
• Serum immunofixation detects only 69% of AL amyloidosis cases, while free light chain assay detects 91% - the combination detects 99% of cases 7
• An abnormal kappa/lambda ratio can occur in 42.5% of patients with chronic kidney disease or proteinuria without myeloma, emphasizing the need for complete workup rather than relying on light chains alone 8
• Renal impairment decreases clearance of both light chains, potentially normalizing an otherwise abnormal ratio and delaying diagnosis 1, 2

Treatment Initiation if Myeloma Confirmed

If diagnostic workup confirms multiple myeloma with renal involvement (light chain cast nephropathy), immediate initiation of bortezomib-based therapy is mandatory to rapidly reduce nephrotoxic light chain production: 4, 9

• Bortezomib plus dexamethasone is the standard regimen, with bortezomib 1.3 mg/m² IV on days 1,4,8, and 11 of 21-day cycles 9
• Rapid reduction of serum free light chains by ≥50-60% within 12-21 days is essential for renal recovery in patients with light chain cast nephropathy 4
• Discontinue all nephrotoxic medications immediately and provide aggressive hydration with urine alkalinization 1

For patients eligible for high-dose therapy (age ≤65, good performance status, no renal failure), autologous stem cell transplantation following induction therapy is standard treatment, with high-dose melphalan 200 mg/m² as the preparative regimen 3

Risk Stratification Once Diagnosed

If myeloma is confirmed, the Revised International Staging System (R-ISS) incorporating beta-2 microglobulin, albumin, LDH, and cytogenetics should guide prognosis and treatment intensity: 4

• An abnormal free light chain ratio ≥100 (for involved kappa) or ≤0.01 (for involved lambda) is considered a myeloma-defining event indicating high-risk disease even without CRAB criteria 2, 4
• Light chain myeloma typically has a more aggressive course and poorer prognosis than intact immunoglobulin myeloma 5