Plasma cell dyscrasia characterised by abnormal clonal proliferation of post-germinal B cells (plasma cells)

Aetiology

• Cause is largely unknown
• Median age at diagnosis - 65 years
• Other risk factors include:
  • Male sex
  • Black African ethnicity
  • Family history
  • Obesity

Pathophysiology

• Plasma cells are B cells (B lymphocytes) of the immune system that have become activated to produce a certain antibody; they are found in the bone marrow
• Myeloma is a cancer of a specific type of plasma cell where there is a genetic mutation causing it to rapidly and uncontrollably multiply
• These plasma cells produce one type of antibody (immunoglobulin)
• When you measure the immunoglobulins in a patient with myeloma, one of those types will be significantly abundant → monoclonal paraprotein
  • More than 50% of the time this is immunoglobulin type G (IgG)
  • The ‘Bence Jones protein’ that can be found in the urine of many patients with myeloma is actually a part (subunit) of the antibody called the light chains

How does myeloma affect the body?

• Myeloma bone disease - dysregulation of bone remodelling leads to the typical lytic lesions, usually seen in the spine, skull, long bones and ribs
  • There is increased osteoclastic activity without increased osteoblast formation of bone, causing fractures of long bones, vertebral collapse and hypercalcaemia
  • Soft tissue plasmacytomas also occur and they are the usual cause of spinal cord compression
• Bone marrow infiltration with plasma cells - results in anaemia, neutropenia, and thrombocytopenia
• Paraprotein secretion - may (rarely) result in symptoms of hyperviscosity
  • In addition, there is a reduction in the levels of normal immunoglobulin (immune paresis), contributing to the tendency to contract recurrent infections
• Myeloma renal disease - 30% of patients have renal impairment at diagnosis, due to a number of factors:
  • Free light chain secretion leads to deposition in the renal tubules, causing renal impairment by cast nephropathy
  • Other factors such as hypercalcaemia, dehydration, use of non-steroidal anti-inflammatory drugs (NSAIDs) and, rarely, the deposition of AL amyloid can also contribute to renal injury

Clinical features

Symptoms

• Bone pain: most commonly backache, owing to vertebral involvement (60%)