What is abnormal in this electrophoresis chart?

Interpretation of Electrophoresis Chart: Monoclonal Gammopathy

The abnormality in this electrophoresis chart is a monoclonal spike (M-spike) in the gamma region, which strongly suggests a monoclonal gammopathy that requires further investigation to determine if it represents multiple myeloma or another plasma cell disorder.

Understanding the Abnormal Pattern

The characteristic finding in the electrophoresis chart is:

• A homogeneous, narrow-based spike in the gamma globulin region
• This represents a monoclonal immunoglobulin (M-protein) produced by a clonal proliferation of plasma cells

This pattern is distinctly different from:

• Normal electrophoresis patterns showing broad-based gamma regions
• Polyclonal gammopathies which show diffuse increases across the gamma region

Diagnostic Significance

This M-spike is the hallmark finding in several conditions 1:

• Multiple myeloma
• Monoclonal gammopathy of undetermined significance (MGUS)
• Smoldering multiple myeloma
• Waldenstrom's macroglobulinemia
• Solitary plasmacytoma
• Amyloidosis
• Heavy chain disease

Required Follow-up Testing

Based on NCCN guidelines 2 and International Myeloma Society recommendations 3, the following workup is essential:

Blood Tests

• Complete blood count with differential
• Comprehensive metabolic panel including:
  • Calcium
  • Creatinine
  • Albumin
  • Total protein
  • LDH
  • Beta-2 microglobulin
• Serum immunofixation electrophoresis (IFE) to identify the specific immunoglobulin type
• Quantitative immunoglobulins (IgG, IgA, IgM)
• Serum free light chain assay with kappa/lambda ratio

Urine Studies

• 24-hour urine collection for:
  • Total protein
  • Urine protein electrophoresis (UPEP)
  • Urine immunofixation electrophoresis (UIFE)

Bone Marrow Examination

• Bone marrow aspirate and biopsy with:
  • Immunohistochemical staining for kappa and lambda
  • Congo red staining for amyloid
  • Cytogenetic studies including FISH for high-risk abnormalities

Imaging Studies

• Whole-body low-dose CT (preferred) or complete skeletal survey
• Consider MRI of spine and pelvis if whole-body CT is negative

Diagnostic Criteria

The diagnosis will depend on findings from the complete workup 3:

1. Multiple Myeloma requires:

   • ≥10% clonal plasma cells in bone marrow OR biopsy-proven plasmacytoma
   • PLUS evidence of end-organ damage (CRAB criteria):
     • Hypercalcemia
     • Renal insufficiency
     • Anemia
     • Bone lesions

2. MGUS is characterized by:

   • <3 g/dL serum M-protein
   • <10% clonal plasma cells in bone marrow
   • No end-organ damage

3. Smoldering Multiple Myeloma:

   • Serum M-protein ≥3 g/dL and/or ≥10% clonal plasma cells
   • No CRAB criteria or other myeloma-defining events

Risk Stratification

For MGUS, risk of progression to multiple myeloma depends on 2:

• M-protein level (>1.5 g/dL is higher risk)
• Type of M-protein (non-IgG is higher risk)
• Abnormal serum free light chain ratio
• Percentage of abnormal plasma cells by flow cytometry

Clinical Pearls

1. The quantity of M-protein alone cannot differentiate between MGUS and multiple myeloma - a complete workup is essential 1.

2. Serum protein electrophoresis is highly sensitive but requires confirmation with immunofixation to identify the specific immunoglobulin type 4.

3. The serum free light chain assay is crucial for detecting light chain myeloma and monitoring disease 3.

4. Even if the M-spike is small, a complete workup is necessary as some patients with multiple myeloma may have small M-protein levels but significant end-organ damage 2.

5. Regular monitoring is essential for patients diagnosed with MGUS or smoldering myeloma to detect progression to symptomatic disease 3.