[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [White cells, lymph nodes, spleen and thymus](https://durgical.com/en/general-pathology/areas/hematolymphoid/) › Multiple myeloma

# Multiple myeloma

- Lesion

Cancer of plasma cells in the bone marrow: it eats bone, raises calcium, harms the kidneys and causes anaemia and infections.

Updated Nov 12, 2026

## Key points

- CRAB: hypercalcaemia, renal failure, anaemia, bone lesions.
- Punched-out lytic lesions, best seen in the skull; generalized osteoporosis is also common.
- Myeloma cells drive RANKL, and inhibit osteoblasts through DKK1; IL-6 is the key growth cytokine.
- Myeloma kidney (cast nephropathy): light chains precipitate in distal tubules with giant-cell reactions; also AL amyloid and hypercalcaemic injury.
- Rouleaux on the smear; recurrent bacterial infections from low normal immunoglobulins.

On this page

- The basics Key points
- What it is
- Structure
- Step by step
- The CRAB features and what causes each
- Markers
- Memory aid
- Elsewhere in DurgiPedia

- Clinical Clinical notes
- In the lab

- Study Test yourself

- Connections Connections

## 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](https://durgical.com/en/conditions/hypercalcaemia-of-malignancy/) | Calcium released from resorbed bone | Confusion, constipation, polyuria |
| Anaemia | Marrow replacement and cytokines | Normocytic anaemia, rouleaux |
| [Kidney injury](https://durgical.com/en/conditions/acute-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.

## Memory aid

Myeloma is CRABby: calcium up, renal down, anaemia, and bones full of holes.

## 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.

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## Elsewhere in DurgiPedia

- [Plasma proteins and electrophoresis](https://durgical.com/en/biochemistry/topics/plasma-proteins-and-electrophoresis/)
- [Immunoglobulins (antibodies)](https://durgical.com/en/biochemistry/enzymes/immunoglobulins/)
- [B cell and plasma cell](https://durgical.com/en/immunology/b-cell-and-plasma-cell/)

## Connections

## Related 4

- [Plasma cell disorders: MGUS to myeloma](https://durgical.com/en/general-pathology/plasma-cell-disorders-mgus-to-myeloma/)
- [Paraneoplastic syndromes: the table to know](https://durgical.com/en/general-pathology/paraneoplastic-syndromes-the-table-to-know/)
- [Pathologic calcification: dystrophic vs metastatic](https://durgical.com/en/general-pathology/pathologic-calcification-dystrophic-vs-metastatic/)
- [Red cell morphology on the smear](https://durgical.com/en/general-pathology/red-cell-morphology-on-the-smear/)

## Related conditions 6

- [Multiple myeloma](https://durgical.com/en/conditions/multiple-myeloma/)
- [Amyloidosis](https://durgical.com/en/conditions/amyloidosis/)
- [Hypercalcaemia of malignancy](https://durgical.com/en/conditions/hypercalcaemia-of-malignancy/)
- [Acute kidney injury](https://durgical.com/en/conditions/acute-kidney-injury/)
- [Malignant spinal cord compression](https://durgical.com/en/conditions/malignant-spinal-cord-compression/)
- [Chronic kidney disease](https://durgical.com/en/conditions/chronic-kidney-disease/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

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](https://medlineplus.gov/ency/article/000583.htm) (MedlinePlus, US National Library of Medicine, 2026); [Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Patient Version](https://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq) (National Cancer Institute (NCI), 2026).

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