Is an elevated IgG level with an M spike, without hypercalcemia or anemia, indicative of multiple myeloma?

Diagnosis: This is NOT Multiple Myeloma

An IgG level of 3887 mg/dL (approximately 3.9 g/dL) with an M-spike, in the absence of hypercalcemia and anemia, does NOT meet diagnostic criteria for multiple myeloma and most likely represents either Monoclonal Gammopathy of Undetermined Significance (MGUS) or Smoldering Multiple Myeloma (SMM), depending on bone marrow plasma cell percentage. 1, 2

Diagnostic Framework

Multiple Myeloma Requires CRAB Criteria

Multiple myeloma diagnosis mandates the presence of end-organ damage, specifically the CRAB criteria 1, 2:

• Calcium elevation (>11.5 mg/dL) - ABSENT in your patient
• Renal insufficiency (creatinine >2 mg/dL or clearance <40 mL/min) - Need to verify
• Anemia (hemoglobin <10 g/dL or ≥2 g/dL below normal) - ABSENT in your patient
• Bone lesions (lytic lesions, severe osteopenia, or pathologic fractures) - Need to verify

Your patient lacks at least 2 of the 4 CRAB criteria, making multiple myeloma diagnosis impossible at this time. 1, 2

Distinguishing MGUS from SMM

The critical distinction depends on two parameters 2:

MGUS criteria:

• M-protein <3 g/dL (30 g/L) 3, 2
• Bone marrow plasma cells <10% 3, 2
• No end-organ damage (no CRAB) 2

SMM criteria:

• M-protein ≥3 g/dL OR bone marrow plasma cells ≥10% 2
• No end-organ damage (no CRAB) 2

Your patient's IgG of 3.9 g/dL exceeds the 3 g/dL threshold, suggesting SMM if bone marrow plasma cells are ≥10%, or potentially high-risk MGUS if plasma cells are <10%. 3, 2

Required Additional Workup

Essential Immediate Testing

You must obtain the following to complete the diagnosis 2, 4:

• Bone marrow aspiration and biopsy - Required for all IgA and IgM cases, and recommended for IgG when M-protein >15 g/L (1.5 g/dL) 2
• Serum free light chain (FLC) assay with kappa/lambda ratio - Critical prognostic marker 3, 4
• Complete skeletal survey (X-rays of spine, pelvis, skull, humeri, femurs) 4
• MRI of spine and pelvis if skeletal survey is negative 2, 4
• 24-hour urine protein electrophoresis (not random sample) 2, 4
• Complete metabolic panel including renal function and calcium 4
• Complete blood count to confirm absence of anemia 4

Risk Stratification

If this proves to be MGUS or SMM, risk of progression depends on 3:

High-risk features (each increases progression risk):

• M-protein ≥15 g/L (1.5 g/dL) - Your patient has 39 g/L, placing them at HIGH RISK 3
• Abnormal serum FLC ratio 3
• IgA or IgM type (IgG is lower risk) - Your patient has IgG, which is favorable 3
• Bone marrow plasma cells >5% (or ≥10% for SMM) 3

Patients with all three risk factors (M-protein ≥15 g/L, non-IgG type, abnormal FLC ratio) have 58% progression risk at 20 years, versus only 5% with no risk factors. 3

Management Implications

If MGUS (plasma cells <10%)

• No immediate treatment required 2
• Lifelong monitoring needed 2
• Progression risk approximately 1% per year 3
• Follow-up intervals based on risk stratification 2

If SMM (plasma cells ≥10%)

• No immediate treatment currently recommended 2
• Much higher progression risk: 10% per year for first 5 years 2
• Requires closer monitoring than MGUS 2
• Follow-up every 3 months for first year to establish disease pattern 2

Critical Pitfalls to Avoid

• Do not diagnose multiple myeloma without documented CRAB criteria - This leads to unnecessary treatment with significant toxicity 1, 2
• Do not skip bone marrow biopsy - Essential for distinguishing MGUS from SMM and ruling out other plasma cell disorders 2
• Do not use random urine samples - 24-hour collection is mandatory for accurate assessment 2, 4
• Do not assume anemia/renal failure is myeloma-related - These may be unrelated to the M-protein and should not trigger myeloma diagnosis without other evidence 3
• Monitor for evolving disease - Progressive increase in M-protein during first year is the single most important predictor of progression 3