Osteosarcoma is the most common malignancy of the bone after haematological and metastatic disease. It is usually divided into conventional osteosarcoma, the more common type that occurs in young people, and secondary osteosarcoma which is related to Paget's disease of bone or radiation exposure. Uncommon variants exist.
Epidemiology
Conventional osteosarcoma has its highest incidence in the teenage years (similar to PNET/Ewing Sarcoma). Men are more commonly affected, and tend to develop the disease earlier. About 30% of cases occur in people over 40 although secondary osteosarcoma must be excluded. It has no other special epidemiological features.
Secondary osteosarcoma is related to its cause.
Aetiology and Pathogenesis
There is no strong evidence linking conventional osteosarcoma to a causative agent. Trauma is often considered to be a suspect but most feel that this simply brings the sarcoma to attention. Similarly, there are no well-identified genetic changes that are commonly found in osteosarcoma, with the lone exception of 17p amplification in about 50% of cases. RB1 and TP53 germline mutations both place people at higher risk for osteosarcoma as well as other malignancies.
Secondary osteosarcoma, by definition, occurs in association a causative factor. This is usually Paget's disease or radiation exposure. Patients with Paget's disease of bone may also have genetic susceptibility to developing osteosarcoma but this is mostly conjecture.
Natural History
Osteosarcoma is highly aggressive with significant local destruction coupled with haematogenous spread, most commonly to the lungs or other bones.
Clinical Presentation
Trauma is often seen as a precursor to diagnosis, this is thought to be unrelated to the disease process. Most commonly patients present with pain (usually deep and constant) and/or a mass that is related to the site of disease. Pulmonary metastases at diagnosis is a very poor prognostic feature.
The ALP level is usually elevated; importantly, in patients with Paget's disease and secondary osteosarcoma it is elevated in excess of the usual levels seen in that disease.
Radiological findings are variable. The most commonly involved site is the metaphysis (growth plate) of long bones, in contrast to PNET which usually involves the diaphysis. The disease is usually confined within the periosteum until late in the course; spread along the medulla of long bones is common.
Tumour/Normal Tissue Features
Macroscopically, the tumour destroys the medulla and cortex of the bone and appears to arise from the metaphysis. Colour is variable.
Microscopically, the most important feature for diagnosis is osteoid. This is dimineralised bone matrix which appears as eosinophilic matter on conventional light microscopy. The malignant cells themselves are typically pleomorphic and have numerous appearances.
There are no good immunohistochemical or genetic tests for osteosarcoma.
Variants
There are a number of variants seen with osteosarcoma:
- Osteoblastic osteosarcoma has a high proportion of osteoid (50% of diagnoses)
- Chondroblastic osteosarcoma has regions of cartilagenous differentiation (20% of diagnoses)
- Fibroblastic osteosarcoma features low amounts of osteoid and a large population of spindle cells (20% of diagnoses)
- Telangiectatic osteosarcoma contains large, blood filled spaces in between the malignant areas of the tumour (<5%)
- Small cell osteosarcoma has features similar to PNET but contains osteiod. (<5%)
Staging / Classification
Staging is through the TNM system. The latest edition (7th):
| T Stage | Description |
|---|---|
| T1 | < 8 cm in maximum dimension |
| T2 | > 8 cm in maximum dimension |
| T3 | Discontinuous tumours in the same bone |
| N Stage | Description |
|---|---|
| N1 | Nodal metastases |
| M Stage | Description |
|---|---|
| M1a | Lung metastases |
| M1b | Other distant metastases |
Grade is also included in TNM staging; most osteosarcomas are of high grade.
| Stage | T | N | M | Grade |
|---|---|---|---|---|
| IA | T1 | N0 | M0 | Low |
| IB | T2 | N0 | M0 | Low |
| IIA | T1 | N0 | M0 | High |
| IIB | T2 | N0 | M0 | High |
| III | T3 | N0 | M0 | Any |
| IVA | Tany | N0 | M1a | Any |
| IVB | Tany | N1 Nany |
Many M1b |
Any |
