Monoclonal gammopathy of undetermined significance

Keywords: MGUS, Monoclonal gammopathy of uncertain significance, Benign monoclonal gammopathy

Key Information

Appropriate Tests

Introduction

Asymptomatic premalignant plasma cell/lymphoplasmacytic proliferative disorder characterised by a serum monoclonal protein of < 30g/L, < 10% plasma cells on bone marrow biopsy, without associated end organ dysfunction (hypercalcaemia, lytic skeletal lesions, renal dysfunction, anaemia and hyperviscosity).

3 major types:

1. Non-IgM MGUS (G, A, D, E) - most common. Risk of progression to smouldering myeloma and symptomatic myeloma; less frequently progresses to AL amyloidosis, light chain deposition disease or another lymphoproliferative disorder.

2. IgM MGUS - risk of progression to Waldenström's macroglobulinaemia (asymptomatic then symptomatic); less often progresses to lymphoma and AL amyloidosis.

3. Light chain MGUS (LC-MGUS) - may progress to idiopathic Bence-Jones proteinuria and to light chain plasma cell myeloma, AL amyloidosis or light chain deposition disease.

Affects approximately 1-2% of adults. Mean age of 70 years. Most cases are sporadic, though there is evidence that first degree relatives of patients with MGUS have a higher incidence of myeloma, lymphoma or Waldenström's macroglobulinaemia.

Usually encountered when patients are screened for a variety of other disorders/symptoms.

Investigations - aimed at excluding end organ damage

  • Full blood count and Blood film
  • Erythrocyte sedimentation rate
  • Serum Creatinine, eGFR and Calcium
  • Serum Protein electrophoresis and Immunofixation
  • Serum Free light chains assay
  • 24 hour urine collection, Protein electrophoresis urine and immunofixation
  • IgG, A and M quantitation.
  • Skeletal survey
  • Beta-2-microglobulin

A bone marrow biopsy is indicated if there are abnormalities indicating possible end organ damage, a monoclonal protein size of > 15g/L, or a non-IgG paraprotein of any level, or if any end organ damage is detected.  Haematology referral is recommended to see if a bone marrow biopsy may be required.

Monitoring

Patients with MGUS should be observed with clinical review, Full blood count, Electrolytes, Calcium, serum EPG, Immunofixation, Bence Jones protein urine and quantitative immunoglobulins every 3-12 months, depending on the age and level of concern in the individual patient.

See Paraproteinaemia and Plasma cell myeloma.