Osteosarcoma
Summary
Osteosarcoma is the most common primary malignant bone tumour, characterised by the production of osteoid (Immature bone) by malignant cells. It has a bimodal age distribution: the majority occur in adolescents/young adults (10-25 years) during periods of rapid bone growth, with a second smaller peak in older adults (>60 years), often secondary to Paget's disease or prior radiation. The most common locations are the metaphysis of long bones around the knee (Distal Femur ~40%, Proximal Tibia ~20%). Patients present with persistent bone pain (Often worse at night), swelling, and occasionally pathological fracture. Imaging shows an aggressive lytic and sclerotic lesion with periosteal reaction (Sunburst, Codman's triangle). Diagnosis requires biopsy. Treatment involves Neoadjuvant Chemotherapy → Limb-sparing surgery/Amputation → Adjuvant Chemotherapy (MAP: Methotrexate, Adriamycin/Doxorubicin, Cisplatin). Prognosis depends on response to chemotherapy (>90% tumour necrosis = Good response) and presence of metastases (Lungs most common). 5-year survival for localised disease is ~70%. [1,2,3]
Clinical Pearls
"Knees Know": Most osteosarcomas occur around the knee – Distal Femur and Proximal Tibia.
"Sunburst + Codman's Triangle": Classic radiographic signs of osteosarcoma. Aggressive periosteal reaction.
"Pain at Night = Red Flag": Night pain / Rest pain suggests aggressive pathology. Think malignancy.
"Chemotherapy Response = Prognosis": >90% tumour necrosis on resection specimen (After neoadjuvant chemo) = Good prognosis.
Demographics
| Factor | Notes |
|---|---|
| Age | Bimodal: Peak 10-25 years (Adolescents). Second peak >60 years (Secondary osteosarcoma). |
| Sex | Male > Female (1.5:1). |
| Incidence | ~3-4 per million per year. Most common primary bone malignancy. |
Location
| Site | Frequency |
|---|---|
| Distal Femur | ~40% |
| Proximal Tibia | ~20% |
| Proximal Humerus | ~10% |
| Other Long Bones | Proximal femur, Pelvis, Jaw (Older adults). |
| Metaphysis | Most common site within long bones. |
Risk Factors
| Risk Factor | Notes |
|---|---|
| Rapid Bone Growth (Puberty) | Association with growth spurts. |
| Paget's Disease | Secondary osteosarcoma in older adults. Rare (less than 1% of Paget's). |
| Prior Radiation | Radiation-induced osteosarcoma. Latency of 10-20 years. |
| Hereditary Syndromes | Li-Fraumeni (TP53), Hereditary Retinoblastoma (RB1), Rothmund-Thomson, Werner. |
Histological Subtypes
| Subtype | Features |
|---|---|
| Conventional (High-Grade Intramedullary) | Most common (~75%). Osteoblastic, Chondroblastic, Fibroblastic variants. |
| Telangiectatic | Lytic, Blood-filled cysts. May mimic aneurysmal bone cyst. |
| Small Cell | Rare. May resemble Ewing sarcoma. |
| Parosteal (Low-Grade Surface) | Arises from periosteum. Well-differentiated. Better prognosis. |
| Periosteal | Intermediate grade. Cartilaginous component. |
| Secondary Osteosarcoma | Arising in Paget's disease, Prior radiation, Chronic osteomyelitis. |
Origin
- Arises from Primitive Mesenchymal Cells that differentiate towards osteoblast lineage.
- Malignant cells produce Osteoid (Unmineralised bone matrix).
Molecular Pathways
| Pathway | Notes |
|---|---|
| RB1 (Retinoblastoma Gene) | Inactivated in many osteosarcomas. |
| TP53 | Mutations common. Li-Fraumeni syndrome. |
| Complex Karyotype | Chromosomal instability. Aneuploidy. |
Metastasis
- Haematogenous spread (Via bloodstream).
- Lungs = Most common metastatic site (~80% of metastases).
- Bone metastases (Skip lesions in same bone, Or other bones).
Symptoms
| Symptom | Notes |
|---|---|
| Pain | Most common. Persistent. Worse at night / Rest. Progressive. |
| Swelling / Mass | Palpable firm mass. May be warm. |
| Reduced Range of Motion | Near joint involvement. |
| Pathological Fracture | ~10% present with fracture through tumour. |
| Limp | If lower limb involved. |
| Systemic Symptoms | Rare early. Weight loss, Fatigue with advanced disease. |
Red Flags
| Red Flag | Notes |
|---|---|
| Night Pain / Rest Pain | Suggests aggressive pathology. |
| Rapidly Growing Mass | Malignancy concern. |
| Pain Not Responding to Simple Analgesia | |
| Symptoms >6 weeks | Persistent symptoms warrant investigation. |
Examination Findings
| Finding | Notes |
|---|---|
| Palpable Mass | Firm, Fixed to bone. May be tender. |
| Overlying Skin Changes | Warmth, Erythema, Dilated veins. |
| Joint Effusion | If near joint. |
| Limited ROM | |
| No Lymphadenopathy | (Bone tumours rarely spread to lymph nodes). |
Imaging
| Modality | Findings |
|---|---|
| X-Ray | Destructive lytic and/or sclerotic lesion. Periosteal reaction: Sunburst pattern, Codman's triangle (Lifted periosteum). "Fluffy" bone formation. Soft tissue mass. |
| MRI | Gold Standard for local staging. Extent of intramedullary involvement. Soft tissue extension. Skip lesions. Relationship to neurovascular structures. |
| CT Chest | Essential for Lung metastases (Most common site). |
| Bone Scan / PET-CT | Assess for bone metastases. PET useful for response assessment. |
Radiographic Signs
| Sign | Description |
|---|---|
| Sunburst/Sunray Pattern | Spiculated periosteal reaction radiating outwards from bone. |
| Codman's Triangle | Triangular elevation of periosteum at edge of tumour. |
| "Fluffy" Bone Formation | Disorganised ossification within tumour. |
| Soft Tissue Mass | Extension beyond cortex. |
Biopsy
| Type | Notes |
|---|---|
| Core Needle Biopsy | Usually sufficient. Planned carefully to avoid contaminating future surgical fields. |
| Open Biopsy | If core inconclusive. Performed by definitive surgeon along surgical approach. |
| Histology | Malignant cells producing osteoid. High-grade spindle cells. |
Staging (Enneking / AJCC)
| Stage | Description |
|---|---|
| IA | Low-grade, Intracompartmental. |
| IB | Low-grade, Extracompartmental. |
| IIA | High-grade, Intracompartmental. |
| IIB | High-grade, Extracompartmental. |
| III | Any grade, Metastatic. |
Management Algorithm
SUSPECTED OSTEOSARCOMA
(Bone pain, Mass, Aggressive X-ray)
↓
STAGING
- X-Ray
- MRI local (Extent, Skip lesions)
- CT Chest (Lung metastases)
- Bone Scan / PET
↓
BIOPSY (Planned by MDT)
- Core needle or Open
- Confirm diagnosis
- Do NOT touch tumour or spread contamination
↓
MULTIDISCIPLINARY TEAM (MDT)
┌────────────────┴────────────────┐
LOCALISED DISEASE METASTATIC DISEASE
↓ ↓
NEOADJUVANT CHEMOTHERAPY CHEMOTHERAPY
(MAP: Methotrexate, +/- Metastasectomy (Lung)
Adriamycin, Cisplatin) +/- Local treatment
8-10 weeks
↓
SURGERY
- Limb-Sparing Resection (Preferred if oncologically safe)
- Wide local excision + Reconstruction (Endoprosthesis, Allograft)
- Amputation (If not limb-sparing candidate)
↓
HISTOLOGICAL RESPONSE ASSESSMENT
(Tumour necrosis in resection specimen)
- Good Response: ≥90% necrosis
- Poor Response: less than 90% necrosis
↓
ADJUVANT CHEMOTHERAPY
(Continue MAP)
↓
SURVEILLANCE
- Regular imaging (CXR, MRI)
- Long-term follow-up
Chemotherapy (MAP Protocol)
| Drug | Notes |
|---|---|
| Methotrexate (High-Dose) | Folate antagonist. Requires Leucovorin rescue. Nephrotoxic, Hepatotoxic. |
| Adriamycin (Doxorubicin) | Anthracycline. Cardiotoxic (Cumulative dose limit). |
| Cisplatin | Platinum agent. Nephrotoxic, Ototoxic. |
Surgery
| Option | Notes |
|---|---|
| Limb-Sparing Surgery | Preferred if wide margins achievable. Requires good response to chemo, No major neurovascular involvement. Reconstruction with endoprosthesis, Allograft, Or combination. |
| Amputation | If limb-sparing not possible (Extensive involvement, Neurovascular encasement, Poor response to chemo). |
| Margins | Wide margins essential. Incomplete excision = High recurrence. |
Metastatic Disease
| Treatment | Notes |
|---|---|
| Lung Metastasectomy | Considered if resectable. Can still achieve long-term survival (~30-40%). |
| Palliative Chemotherapy | For unresectable disease. |
Disease-Related
| Complication | Notes |
|---|---|
| Pathological Fracture | May present at diagnosis or during treatment. |
| Lung Metastases | Most common cause of death. |
| Local Recurrence | If inadequate margins. |
Treatment-Related
| Complication | Notes |
|---|---|
| Chemotherapy Toxicity | Cardiotoxicity (Doxorubicin), Nephrotoxicity (Cisplatin, Methotrexate), Ototoxicity, Myelosuppression, Infertility. |
| Surgical Complications | Infection, Non-union, Prosthesis failure, Limb-length discrepancy. |
| Late Effects | Secondary malignancy, Cardiac disease, Renal impairment. |
| Factor | Notes |
|---|---|
| Localised Disease (No Metastases) | 5-year survival ~60-70%. |
| Metastatic at Diagnosis | 5-year survival ~20-30%. |
| Chemotherapy Response (>90% Necrosis) | Better prognosis. ~80% survival. |
| Poor Response (less than 90% Necrosis) | Worse prognosis. ~50% survival. |
| Resectable Lung Metastases | Survival improved with complete metastasectomy. |
| Axial Location (Pelvis) | Worse prognosis than appendicular. |
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Bone Sarcoma | NICE / ESMO | MDT management. Neoadjuvant + Adjuvant chemotherapy. Limb-sparing surgery where possible. |
| Bone Tumour Referral | NICE NG12 | Urgent referral pathway for suspected bone cancer. |
Landmark Trials
| Finding | Notes |
|---|---|
| Chemotherapy + Surgery >> Surgery Alone | Addition of chemotherapy dramatically improved survival from ~20% to ~70% for localised disease. |
| Limb-Sparing = Amputation (Survival) | No difference in survival between limb-sparing surgery and amputation if margins adequate. |
What is Osteosarcoma?
Osteosarcoma is a type of bone cancer. It most commonly affects teenagers and young adults during their growth years, and typically occurs around the knee.
What are the symptoms?
- Bone pain – Persistent, Often worse at night.
- Swelling or a lump near a joint.
- Limping if in the leg.
- Rarely, a fracture through the weakened bone.
If pain persists for more than a few weeks, especially with night pain, see your doctor.
How is it treated?
Treatment usually involves:
- Chemotherapy first (To shrink the tumour).
- Surgery (To remove the tumour – Usually limb-sparing surgery, Sometimes amputation).
- More chemotherapy (After surgery).
Can the limb be saved?
In most cases (~80%), surgeons can remove the tumour while saving the limb. The bone is replaced with a metal prosthesis or bone graft.
What is the outlook?
For osteosarcoma that has not spread, about 7 out of 10 people are cured. If it has spread to the lungs, treatment is still possible but cure rates are lower.
Primary Sources
- Mirabello L, et al. Osteosarcoma incidence and survival rates from 1973 to 2004. Cancer. 2009;115(7):1531-1543. PMID: 19197972.
- Bielack SS, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk. J Clin Oncol. 2002;20(3):776-790. PMID: 11821461.
- ESMO/European Sarcoma Network Working Group. Bone sarcomas: ESMO-PaedCan-EURACAN Clinical Practice Guidelines. Ann Oncol. 2021;32(12):1520-1536. PMID: 34500020.
Common Exam Questions
- Most Common Location: "Where does osteosarcoma most commonly occur?"
- Answer: Distal Femur and Proximal Tibia (Around the knee).
- Radiographic Signs: "What are the classic X-ray findings?"
- Answer: Sunburst/Sunray periosteal reaction, Codman's triangle, Lytic + Sclerotic lesion, Soft tissue mass.
- Chemotherapy Response: "What indicates a good response to neoadjuvant chemotherapy?"
- Answer: ≥90% tumour necrosis in the resection specimen.
- Metastatic Site: "What is the most common site of metastasis?"
- Answer: Lungs.
Viva Points
- Age Distribution: Bimodal. Young (Adolescent) + Older (Secondary to Paget's/Radiation).
- Metaphysis: Most common location within bone.
- Limb-Sparing vs Amputation: No survival difference if margins adequate. Limb-sparing preferred.
- Biopsy Planning: Crucial. Biopsy tract must be excised with tumour. Plan with MDT.
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