Makindo Medical Notes

Related Subjects: |Hypercalcaemia |Multiple Myeloma |Extramedullary Plasmacytoma |Smouldering Myeloma |MGUS |Waldenstrom Macroglobulinaemia |Oncological emergencies

🧪 Monoclonal Gammopathy of Undetermined Significance (MGUS) is a benign paraproteinaemia defined by a serum monoclonal protein < 30 g/L, < 10% plasma cells in the marrow, and no end-organ damage (CRAB: hyperCalcaemia, Renal failure, Anaemia, Bone lesions). The key differentiating feature from myeloma is the absence of complications such as immune paresis, hypercalcaemia, renal impairment, or bone disease.

📖 About

• MGUS is a paraproteinaemia that may progress to myeloma.
• Serum monoclonal protein < 30 g/L, plasma cells < 10%.
• Progression to myeloma may take years (≈1% per year risk).

📊 Epidemiology

• Asymptomatic and very common in older adults.
• ~1% prevalence over age 25, 3% >70 yrs, 10% >80 yrs.
• Only ~25% of cases progress to myeloma.

🔎 Differential Diagnosis of a Monoclonal Band

• 🦴 Multiple Myeloma: Bone pain, lytic lesions, hypercalcaemia, renal disease.
• 🧬 Lymphoma: Lymphadenopathy, hepatosplenomegaly.
• 🧪 Chronic Lymphocytic Leukaemia (CLL): Raised lymphocyte count.
• 🟢 MGUS: Asymptomatic, low paraprotein, no CRAB features.

⚡ Clinical Features

• Typically none due to MGUS itself.
• No bone pain or recurrent infections.
• 10–30% may have a demyelinating neuropathy.

🚫 In MGUS there is NO:

• Bence-Jones proteinuria.
• Lytic bone lesions.
• Hypercalcaemia.
• Renal insufficiency.
• Anaemia.
• Monoclonal Ig level > 30 g/L.
• Plasma cells > 10% on bone marrow exam.
• Immunoparesis (suppression of other Ig classes).

📈 Risk of Progression

• ~1% of patients progress to myeloma each year.
• Risk factors for progression include paraprotein type and level, and serum free light chain ratio.

🧮 Risk Stratification – “Mayo Model”

• Paraprotein > 15 g/L ➕ 1 point.
• Abnormal free light chain ratio ➕ 1 point.
• Non-IgG paraprotein (IgA, IgM, IgE) ➕ 1 point.

📊 20-Year Risk of Progression

• 0 factors → 5%.
• 1 factor → 21%.
• 2 factors → 37%.
• 3 factors → 58%.

🧾 Management

• Low-risk MGUS (0–1 risk factors) can be managed in primary care.
• Follow-up every 6–12 months:
  • History: weight loss, night sweats, bone pain.
  • Examination: lymphadenopathy, hepatosplenomegaly.
  • Tests: FBC, calcium, creatinine, albumin, SPE with paraprotein quantification.
• Refer to haematology if:
  • Lymphadenopathy.
  • Significant paraprotein rise (>25% & absolute rise >5 g/L).
  • New cytopenias (anaemia, neutropenia, thrombocytopenia).
  • Renal impairment or new bone pain.

Cases — MGUS (Monoclonal Gammopathy of Undetermined Significance)

• Case 1 — Incidental Finding in the Elderly: A 72-year-old man has routine bloods before cataract surgery. Serum protein electrophoresis shows a small monoclonal IgG kappa paraprotein (12 g/L). Hb, calcium, creatinine, and skeletal survey are normal. He is asymptomatic. Diagnosis: MGUS, requires monitoring for progression.
• Case 2 — Workup for Anaemia: A 65-year-old woman is investigated for mild normocytic anaemia. SPEP reveals a monoclonal IgA lambda band of 18 g/L. Bone marrow biopsy shows plasma cells <10%. No lytic lesions, renal impairment, or hypercalcaemia. Diagnosis: MGUS, not myeloma.

Teaching Commentary 🧬

MGUS is a benign clonal plasma cell disorder defined by: - Serum monoclonal protein <30 g/L, - <10% plasma cells in bone marrow, - No CRAB features (hyperCalcaemia, Renal impairment, Anaemia, Bone lesions). It is common in older adults (≈3–5% over age 70). MGUS is usually asymptomatic but carries a risk (~1% per year) of progression to multiple myeloma or related disorders. Management: no treatment, but regular monitoring with FBC, renal function, calcium, and paraprotein levels to detect progression early.