Multiple myeloma
- Lesion
Cancer of plasma cells in the bone marrow: it eats bone, raises calcium, harms the kidneys and causes anaemia and infections.
What it is
Multiple myeloma is a neoplasm of plasma cells that fills the marrow and forms many lytic bone lesions, mostly in the axial skeleton. It secretes an M protein (IgG, IgA or free light chains) and suppresses normal antibodies. The tumour activates osteoclasts and inhibits osteoblasts, causing bone pain, fractures and hypercalcaemia; light chains injure the kidney. It is a disease of older adults and is commoner in people of African descent.
Structure
- Bone: soft red gelatinous tumour filling round lytic defects without a sclerotic rim.
- Marrow: sheets of plasma cells, often with atypia: binucleate cells, prominent nucleoli, flame cells, Mott cells.
- Inclusions: Russell bodies (cytoplasmic immunoglobulin globules) and Dutcher bodies (nuclear).
- Kidney: tubular casts of light chains surrounded by multinucleated giant cells; interstitial inflammation.
Step by step
- A plasma cell clone with an IGH translocation (cyclin D1, cyclin D3, FGFR3/MMSET, MAF) or hyperdiploidy expands from an MGUS stage.
- Marrow stromal cells supply IL-6; the clone grows and replaces the marrow.
- Tumour cells raise RANKL and lower osteoprotegerin and osteoblast activity: bone dissolves.
- Calcium released from bone raises serum calcium; light chains filtered by the kidney form toxic casts.
- Normal antibody production falls and the marrow fails: infections and anaemia.
The CRAB features and what causes each
| Feature | Mechanism | What you see |
|---|---|---|
| Bone lesions | Osteoclast activation through RANKL; osteoblast suppression | Punched-out lytic lesions, fractures, bone pain |
| Hypercalcaemia | Calcium released from resorbed bone | Confusion, constipation, polyuria |
| Anaemia | Marrow replacement and cytokines | Normocytic anaemia, rouleaux |
| Kidney injury | Light-chain casts, amyloid, hypercalcaemia, infections | Rising creatinine, Bence Jones proteinuria |
| Infections | Suppressed normal immunoglobulins | Recurrent pneumonia and urinary infections with encapsulated bacteria |
Markers
- CD138
- CD38
- Light-chain restriction
- CD56 (aberrant)
Clinical notes
- Back pain or a pathologic fracture in an older adult with anaemia and high total protein.
- Vertebral collapse can cause spinal cord compression.
- Survival has improved greatly with modern therapy.
In the lab
- M spike on serum electrophoresis; Bence Jones proteins (free light chains) in urine.
- About one in five patients secretes only free light chains, so a normal serum electrophoresis does not exclude myeloma.
Test yourself
Think of the answer, then tap the question to see it.
How does myeloma destroy bone?
Tumour cells increase RANKL to activate osteoclasts and secrete inhibitors (such as DKK1) that block osteoblasts.
What is cast nephropathy?
Tubular obstruction and injury by precipitated monoclonal light chains, surrounded by giant-cell reactions.
What are Russell bodies?
Cytoplasmic globules of immunoglobulin in plasma cells; Dutcher bodies are the nuclear equivalent.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Multiple myeloma: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Patient Version (National Cancer Institute (NCI), 2026).
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Representative model, for educational purposes only.