Osteosarcoma
- Lesion
The commonest primary bone cancer of children and teens: malignant cells that make osteoid, usually around the knee, spreading to the lungs.
What it is
Osteosarcoma is a malignant tumour whose cells produce osteoid or bone. It has two age peaks: most cases are in adolescents during the growth spurt, at the metaphysis of the distal femur, proximal tibia or proximal humerus; a second peak in older adults arises in bone damaged by Paget disease, radiation or infarcts. Its genetics are complex, with frequent loss of RB1 and TP53 and amplification of CDK4 or MDM2 in some types; people with hereditary retinoblastoma or Li-Fraumeni syndrome have a high risk. It spreads by the blood, mostly to the lungs.
Structure
- Gross: gritty, grey-white mass in the metaphysis with haemorrhage and necrosis, breaking through cortex and lifting periosteum; usually stops at the growth plate.
- Micro: pleomorphic cells with large hyperchromatic nuclei, bizarre giant cells and many atypical mitoses.
- Neoplastic osteoid is pink and lace-like, laid down directly by tumour cells and permeating host bone.
- Some tumours also make malignant cartilage (chondroblastic) or are mostly spindle cells (fibroblastic); telangiectatic osteosarcoma is blood-filled and mimics an aneurysmal bone cyst.
- Surface variants: parosteal (low grade, on the posterior distal femur) and periosteal.
Step by step
- Rapidly dividing osteoprogenitor cells in growing bone are exposed to mutations.
- Loss of RB1 and TP53 removes the main cell-cycle brakes and the DNA damage response.
- Genomic instability creates many structural changes and amplifications.
- Malignant cells make osteoid and destroy cortex, lifting the periosteum.
- Tumour cells enter marrow sinusoids and veins and seed the lungs; skip lesions can form in the same bone.
Osteosarcoma and its look-alikes
| Lesion | Age | Site | Key difference |
|---|---|---|---|
| Conventional osteosarcoma | Teens | Metaphysis near the knee | Atypical cells making lace-like osteoid; permeates host bone |
| Secondary osteosarcoma | Older adults | Pagetic or irradiated bone | Same histology, worse outcome |
| Osteoblastoma | Young people | Spine posterior elements | No atypia, no permeation |
| Fracture callus | Any | Fracture site | Orderly zones, history and X-ray of fracture |
| Ewing sarcoma | Children | Diaphysis, pelvis | Small round blue cells, no osteoid, CD99 |
Markers
- SATB2 (osteoblastic differentiation)
- MDM2 and CDK4 (low-grade types)
- Alkaline phosphatase in serum
Clinical notes
- Painful, enlarging mass around the knee in a teenager, sometimes with a pathologic fracture.
- Treatment is neoadjuvant chemotherapy, limb-sparing surgery and further chemotherapy; tumour necrosis after chemotherapy predicts outcome.
- Lung metastases are present at diagnosis in a minority and determine prognosis.
Test yourself
Think of the answer, then tap the question to see it.
What histologic finding defines osteosarcoma?
Malignant tumour cells directly producing osteoid or bone.
Which inherited syndromes raise the risk of osteosarcoma?
Hereditary retinoblastoma (RB1) and Li-Fraumeni syndrome (TP53).
What is a Codman triangle?
Reactive bone at the edge where the tumour lifts the periosteum off the cortex.
Where does osteosarcoma usually metastasize?
To the lungs, by the blood.
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: Osteosarcoma and Undifferentiated Pleomorphic Sarcoma of Bone Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2025); Primary Bone Cancer - NCI (National Cancer Institute, 2025).
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Representative model, for educational purposes only.