What is the most likely diagnosis and appropriate work‑up and treatment for a patient with a lytic wrist lesion and elevated serum free kappa and lambda light chains?

Elevated Free Kappa and Lambda Chains with Lytic Wrist Lesion

The most likely diagnosis is a plasma cell disorder—either solitary plasmacytoma of bone or light chain multiple myeloma—and you must immediately obtain a tissue biopsy of the wrist lesion with immunohistochemistry, bone marrow aspiration and biopsy with flow cytometry, complete skeletal imaging, and comprehensive protein studies to distinguish between these entities and guide treatment. 1

Most Likely Diagnosis

The combination of a lytic bone lesion and elevated serum free light chains strongly suggests a plasma cell neoplasm. The differential includes:

• Solitary plasmacytoma of bone (SPB) if this represents an isolated lesion 1
• Light chain multiple myeloma if additional lesions or bone marrow involvement >10% is present 1, 2
• Multiple myeloma with oligosecretory disease if both kappa and lambda are elevated but with an abnormal ratio 3, 4

Critical distinction: Elevation of both kappa and lambda chains can occur in plasma cell disorders when there is concurrent renal impairment causing polyclonal elevation superimposed on monoclonal production, or rarely in biphenotypic myeloma 3, 5, 6. The kappa/lambda ratio is the key discriminator—a ratio outside 0.26-1.65 indicates monoclonality despite elevation of both chains 3, 4.

Immediate Diagnostic Work-Up

Tissue Diagnosis (Highest Priority)

• Biopsy of the wrist lesion with histological confirmation of monoclonal plasma cell infiltration using CD138 and/or CD38 immunohistochemistry 1
• Prove monoclonality by kappa/lambda light chain restriction on immunohistochemistry or PCR-based approach 1
• This is mandatory and cannot be bypassed—tissue diagnosis is required for definitive diagnosis of plasmacytoma 1

Bone Marrow Evaluation

• Unilateral bone marrow aspiration and trephine biopsy to quantify plasma cell percentage 1
• Flow cytometry on bone marrow aspirate to detect aberrant clonal plasma cells—this has critical prognostic significance, as 68-71% of patients with occult bone marrow disease progress to multiple myeloma versus only 8-12.5% without 1
• Cytogenetic analysis and FISH for del(13q), t(4;14), t(14;16), del(17p), and 1q21 amplification for risk stratification 1, 4
• >10% clonal plasma cells = multiple myeloma diagnosis, not solitary plasmacytoma 1

Comprehensive Protein Studies

• Serum protein electrophoresis (SPEP) with immunofixation (SIFE) 1, 4
• 24-hour urine collection for total protein, urine protein electrophoresis (UPEP), and urine immunofixation (UIFE)—this cannot be replaced by spot urine or serum FLC alone 1, 5
• Quantitative immunoglobulins (IgG, IgA, IgM) 1
• Repeat serum free light chain assay and calculate the kappa/lambda ratio—a ratio >100 or <0.01 is a myeloma-defining event even without other CRAB criteria 3, 4, 5

Complete Skeletal Imaging

• Full skeletal survey (or preferably whole-body low-dose CT or MRI) to detect additional lytic lesions 1, 4
• MRI of spine and pelvis is mandatory for all patients with suspected solitary plasmacytoma to exclude occult lesions 1
• Detection of additional lesions changes the diagnosis from solitary plasmacytoma to multiple myeloma 1

Laboratory Assessment for End-Organ Damage (CRAB Criteria)

• Complete blood count to assess for anemia (hemoglobin <10 g/dL or ≥2 g/dL below normal) 1
• Serum calcium (>11.5 mg/dL indicates hypercalcemia) 1
• Serum creatinine and estimated GFR (creatinine >2 mg/dL or GFR <40 mL/min indicates renal insufficiency) 1
• Beta-2 microglobulin, albumin, and LDH for International Staging System (ISS) and Revised ISS prognostication 1, 5

Treatment Algorithm

If Solitary Plasmacytoma of Bone (Single Lesion, <10% BM Plasma Cells, No CRAB)

• Radiotherapy is the primary treatment for solitary plasmacytoma 1
• Close surveillance with serial imaging and protein studies, as 49-68% have occult bone marrow disease and are at high risk for progression to myeloma 1
• Median time to progression is 26 months in those with aberrant bone marrow plasma cells by flow cytometry 1

If Multiple Myeloma (≥10% BM Plasma Cells OR Multiple Lesions OR CRAB Criteria Present)

• Immediate systemic therapy is required 1
• Treatment regimen depends on transplant eligibility, cytogenetic risk, and renal function 1
• If acute kidney injury with serum FLC >80-200 mg/dL: Urgent bortezomib-containing regimen to rapidly reduce FLC by ≥50-60% within 12-21 days for renal recovery 3, 5

Critical Pitfalls to Avoid

• Never rely on serum FLC assay alone—always combine with SPEP, SIFE, UPEP, and UIFE, as FLC assay can miss certain monoclonal proteins 3, 4
• Do not skip the tissue biopsy—diagnosis of plasmacytoma requires histological confirmation of monoclonal plasma cells 1
• Renal impairment causes polyclonal elevation of both kappa and lambda chains—always check the kappa/lambda ratio and assess renal function 3, 4, 5
• Flow cytometry on bone marrow has critical prognostic value—it distinguishes true solitary plasmacytoma (negative flow, 8% progression risk) from occult myeloma (positive flow, 71% progression risk) 1
• MRI of spine and pelvis is mandatory for suspected solitary plasmacytoma—it detects occult lesions that change the diagnosis to myeloma 1
• If the patient is receiving daratumumab therapy, be aware it interferes with serum protein electrophoresis and immunofixation, potentially causing false-positive results in IgG kappa myeloma patients 7
• Use the same assay for serial FLC monitoring to ensure accurate comparison over time 1, 4, 5