Osteosarcoma

Classic Osteosarcoma (Intramedullary)

Epidemiology

• Male-to-female ratio: 1.5:1
• Common in young adults and children

Aetiology

• Exact cause unknown
• Associated with retinoblastoma gene and p53 translocation

Location

• Intramedullary meta-diaphyseal junction origin is classic
• Most common around the knee
• Less common in proximal humerus, proximal femur, and pelvis

Presentation

• Short history of pain
• Mass
• Symptoms may appear after an acute injury
• Pathologic fracture in 10% of cases
• 20% of patients have lung metastases at presentation

Imaging

XR

• Simultaneous bone formation and lysis
• Codman's triangle (elevated periosteum)
• Sunray spicules (tumor invasion into bone remodeling)
• Lesions may be sclerotic, lytic, or mixed

CXR

• Evaluate for pulmonary metastases.

MRI

• Assess neurovascular involvement, aid surgical planning, and identify skip lesions.

Bone Scan

• Screen for bony metastases and skip lesions.

CT

• Used for staging the chest, abdomen, and pelvis.

Histology

• Intramedullary osteosarcoma is high grade
• All osteosarcomas originate from spindle cells
• Diagnosis requires the presence of malignant osteoid
• Features include:
  • Pleomorphic cells (altered size and shape)
  • Dark-stained nuclei
  • Poorly differentiated nuclei
  • High mitotic activity
  • Invasion into surrounding tissues

Management

• Neo-adjuvant chemotherapy: Administered for 6–12 weeks to induce tumor necrosis and stabilize the reactive zone
• Re-staging of tumor
• Surgical excision: Wide or radical excision based on stage and tumor necrosis
• Adjuvant chemotherapy
• Amputation: Only if the limb is unsalvageable
• Limb salvage: Achievable in 90% of cases today
• Lung metastases: Isolated cases are potentially resectable

Outcomes

Poor Prognostic Indicators

1. High LDH levels
2. High alkaline phosphatase levels
3. No DNA alteration post-chemotherapy
4. Vascular invasion
5. Metastases at presentation (bone worse than lung)
6. Local recurrence or incomplete margins
7. Expression of P-glycoprotein
8. Absence of anti-shock protein 90 antibodies post-chemotherapy
9. Presentation with pathologic fractures (higher recurrence rates)
10. Pelvic location

Good Prognostic Indicators

1. No metastases and intracompartmental at presentation
2. 90% tumor necrosis after neo-adjuvant chemotherapy

Outcome Statistics

• Overall 5-year survival: 70%
• Pelvic osteosarcoma 5-year survival: 25%
• Metastatic presentation 5-year survival: 20%
• Local recurrence and bone metastases indicate poor long-term survival

Intramedullary, Paraosteal, and Periosteal Osteosarcoma

Osteosarcoma Subtypes