[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Bones, joints and soft tissue](https://durgical.com/en/general-pathology/areas/bone-soft/) › Giant cell tumour of bone

# Giant cell tumour of bone

- Lesion

A locally aggressive tumour at the ends of long bones in young adults: mutant stromal cells call in huge numbers of osteoclast-like cells.

Updated Nov 12, 2026

## Key points

- Age 20–40; epiphysis of long bones after closure of the growth plate (distal femur, proximal tibia, distal radius).
- X-ray: eccentric lytic lesion reaching the subchondral bone, with a 'soap bubble' look and thin or absent rim.
- Neoplastic cell = mononuclear stromal cell with H3-3A G34W mutation; the giant cells are reactive osteoclasts.
- Stromal cells express RANKL; denosumab (anti-RANKL antibody) shrinks the tumour.
- Local recurrence after curettage is common; benign lung implants occur rarely; true malignant transformation is rare.
- Giant cells also appear in brown tumour, aneurysmal bone cyst and chondroblastoma: context matters.

## What it is

Giant cell tumour of bone is a benign but locally aggressive tumour of young adults, after the growth plate has closed. It arises in the epiphysis, extending into the metaphysis, most often around the knee and the distal radius. The neoplastic cells are mononuclear stromal cells with a mutation in the histone gene H3-3A (formerly H3F3A, usually G34W); they express RANKL and recruit the many non-neoplastic osteoclast-type giant cells that destroy bone. It recurs after curettage and rarely implants in the lungs as benign nodules.

## Structure

- Gross: red-brown, haemorrhagic, often cystic mass that expands the bone end and thins the cortex.
- Micro: evenly spread osteoclast-type giant cells with dozens of nuclei in a sea of oval mononuclear cells.
- The nuclei of the mononuclear cells match those of the giant cells.
- Haemorrhage, haemosiderin, foamy macrophages and reactive bone at the edge; necrosis and mitoses can occur without malignancy.

## Step by step

- A mesenchymal stromal cell acquires an H3-3A mutation that alters gene expression.
- Mutant stromal cells proliferate and express high RANKL.
- RANKL recruits monocytes and fuses them into osteoclast-type giant cells.
- Giant cells resorb the bone end and expand it toward the joint.
- Blocking RANKL removes the giant cells and lets bone re-form.

## Markers

- H3.3 G34W immunostain in stromal cells

## Clinical notes

- Knee or wrist pain and swelling in a young adult, sometimes with pathologic fracture.
- Treated by curettage with adjuvants and filling; denosumab is used for unresectable tumours.
- Before calling a giant-cell lesion a giant cell tumour, rule out hyperparathyroidism (brown tumour).

## Memory aid

Giant cell tumour: the giants are hired muscle; the real boss is the small stromal cell holding RANKL.

## Test yourself

Think of the answer, then tap the question to see it.

## Which cell is neoplastic in giant cell tumour of bone?

The mononuclear stromal cell, which carries an H3-3A (H3.3 G34W) mutation.

## Why does denosumab work in giant cell tumour?

The stromal cells drive osteoclast-type giant cells through RANKL; denosumab blocks RANKL.

## Where and at what age does giant cell tumour arise?

In the epiphysis of long bones of young adults (20–40) after growth plate closure.

## Which other lesion must be excluded with blood tests?

Brown tumour of hyperparathyroidism.

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## Elsewhere in DurgiPedia

- [Bone remodeling](https://durgical.com/en/physiology/bone-remodeling/)

## Connections

## Related 5

- [Benign vs malignant tumours: the comparison table](https://durgical.com/en/general-pathology/benign-vs-malignant-tumours-the-comparison-table/)
- [Bone tumours at a glance](https://durgical.com/en/general-pathology/bone-tumours-at-a-glance/)
- [Fibrous dysplasia and other fibrous and cystic bone lesions](https://durgical.com/en/general-pathology/fibrous-dysplasia-and-other-fibrous-and-cystic-bone-lesions/)
- [Bone in hyperparathyroidism and renal osteodystrophy](https://durgical.com/en/general-pathology/bone-in-hyperparathyroidism-and-renal-osteodystrophy/)
- [Joint cysts and tenosynovial giant cell tumour](https://durgical.com/en/general-pathology/joint-cysts-and-tenosynovial-giant-cell-tumour/)

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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: [Primary Bone Cancer - NCI](https://www.cancer.gov/types/bone/bone-fact-sheet) (National Cancer Institute, 2025).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/giant-cell-tumour-of-bone/