What are the symptoms of Monoclonal Gammopathy of Undetermined Significance (MGUS) versus multiple myeloma?

Symptoms of MGUS vs Multiple Myeloma

MGUS is asymptomatic by definition, while multiple myeloma presents with end-organ damage characterized by hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB criteria). 1, 2

MGUS (Monoclonal Gammopathy of Undetermined Significance)

• No clinical manifestations/symptoms - MGUS is defined by the absence of symptoms or end-organ damage 1, 2

• Laboratory findings only:

  • Serum monoclonal protein <3 g/dL 1, 2
  • Bone marrow clonal plasma cells <10% 1, 2
  • No evidence of end-organ damage 1

• Potential complications - While MGUS is technically asymptomatic, it can occasionally be associated with:

  • Peripheral neuropathy (especially with IgM MGUS) 1
  • Renal disorders (monoclonal immunoglobulin deposition disease) 1
  • Blood disorders (cold agglutinin disease, immune thrombocytopenia) 1
  • Increased risk of infections 1
  • Increased risk of venous/arterial thrombosis 1
  • Osteoporosis 1

Multiple Myeloma

• End-organ damage (CRAB criteria) - The hallmark symptoms of multiple myeloma include: 1, 2

  • C: Hypercalcemia (serum calcium >11.5 mg/dL) 2
    • Symptoms: nausea, vomiting, confusion, polyuria, constipation
  • R: Renal insufficiency (creatinine >2 mg/dL or clearance <40 mL/min) 2
    • Symptoms: edema, fatigue, decreased urine output
  • A: Anemia (hemoglobin <10 g/dL or 2 g/dL below lower limit of normal) 2
    • Symptoms: fatigue, weakness, pallor, dyspnea
  • B: Bone lesions (lytic lesions, severe osteopenia, pathologic fractures) 2
    • Symptoms: bone pain (especially back pain), pathologic fractures

• Additional clinical manifestations:

  • Recurrent bacterial infections due to immunodeficiency 1
  • Extramedullary plasmacytomas (soft tissue masses) 1
  • Hyperviscosity syndrome (with high M-protein levels) 3
  • Neurological symptoms from spinal cord compression 3

Smoldering Multiple Myeloma (SMM) - Intermediate Stage

• No clinical manifestations/symptoms - Like MGUS, SMM has no symptoms 1, 2
• Laboratory findings:
  • Serum monoclonal protein ≥3 g/dL and/or 1
  • Bone marrow clonal plasma cells 10-60% 1
  • No evidence of end-organ damage 1
• Higher risk of progression - 10% per year for the first 5 years (versus 1% per year for MGUS) 1, 2

Diagnostic Pitfalls

• Mimicking conditions - Several conditions can mimic myeloma symptoms: 1

  • Mild increase in serum creatinine from diabetes or hypertension 1
  • Anemia from iron, vitamin B12, or folic acid deficiency 1
  • Diffuse osteoporosis (especially in elderly women) 1
  • Hyperparathyroidism causing hypercalcemia 1
  • Benign bone cysts or angiomas mimicking lytic lesions 1

• Key distinguishing factor - The critical difference is that in MGUS and SMM, any laboratory abnormalities or clinical features cannot be attributed to the plasma cell disorder, while in multiple myeloma, they are directly caused by it 1

Monitoring and Progression

• MGUS progression risk - Approximately 1% per year risk of progression to multiple myeloma or related disorders 1
• SMM progression risk - Approximately 10% per year for the first 5 years, 3% per year for the next 5 years, and 1% per year thereafter 1
• Myeloma-defining events - Patients with any of these findings are now considered to have multiple myeloma requiring therapy: 4
  • Bone marrow plasma cell percentage ≥60% 4
  • Free light-chain ratio ≥100 4

  • 1 focal lesion on MRI 4