Question
Osteosarcoma
Answer
Osteosarcoma is the most common primary malignant bone tumour, arising in the metaphysis of long bones (distal femur, proximal tibia, proximal humerus) with a bimodal age distribution (peak in adolescents/young adults; a second smaller peak in older adults, often secondary to Paget disease or prior irradiation).
Aetiology/risk factors: Rapid bone growth (adolescent peak), RB gene mutations (retinoblastoma survivors have markedly increased risk), TP53 mutations (Li-Fraumeni syndrome), Paget disease of bone, prior radiation exposure.
Gross: Grey-white, gritty (due to bone/osteoid formation), haemorrhagic and necrotic mass destroying the cortex and extending into surrounding soft tissue; wide zone of transition with surrounding bone.
Radiology:
- Destructive, mixed lytic-blastic lesion in the metaphysis.
- Codman triangle — periosteal elevation at the tumour margin.
- Sunburst/sunray appearance — radiating spicules of reactive bone.
Microscopy:
- Anaplastic, pleomorphic spindle/polygonal malignant cells with marked nuclear atypia and numerous, often abnormal, mitoses.
- Hallmark: direct production of osteoid/immature woven bone by malignant tumour cells (diagnostic feature).
- Chondroblastic and fibroblastic differentiation may coexist.
- Areas of necrosis, haemorrhage, and vascular invasion.
Clinical: Presents with localized bone pain (worse at night, may follow minor trauma) and swelling; elevated serum alkaline phosphatase. Metastasizes early and haematogenously, chiefly to the lungs. Treated with neoadjuvant chemotherapy plus limb-sparing surgical resection; survival has improved markedly with combined modality treatment.