Diagnosis

Osteosarcoma

Etiology

Cause [g5i]

• Primary osteosarcoma originates within normal bone (childhood and adolescence):

  • Unknown cause

  • Possible theories:

    • Genetic predisposition

    • Enviromental factors

• Secondary osteosarcoma originates in bone affected by a disease:

  • Paget disease of bone

  • Radiation exposure

  • Case reports: history of electrical burns, trauma, and joint arthroplasty

Pathophysiology [g5i]

1. Localization:

   • Primary: Near the growth plates of long bones (femur, tibia, humerus)

     Rapid bone growth during adolescence --> Increased risk of DNA mutation

   • Secondary: Skull, jaw, and pelvis, primarily the ilium

     Inflammation --> Increased risk of DNA mutation

2. Sporadic mutation in the tumor suppressor genes

3. Regulatory mechanisms become defective

4. Uncontrolled cellular proliferation of a single clone of bone cells

5. Osteosarcoma usually starts in osteoblasts

6. Clinical presentation: bone pain, swelling, pathological fracture

Risk factors [g5i]

• Past treatment with chemotherapy or radiation therapy

• RB1 gene

• Bloom syndrome

• Diamond-Blackfan anemia

• Li-Fraumeni syndrome

• Paget disease

• Hereditary retinoblastoma

• Rothmund-Thomson syndrome

• Werner syndrome

Complications [g5i]

• Metastasis (10-20% present with metastases, primarily to the lungs)

• Pathologic fracture

• Treatment complications

Classification of bone tumors

• Malignant: Osteosarcoma, Chondrosarcoma, Ewings Tumor

• Benign: Osteoid Osteoma, Osteoblastoma, Osteochondroma, Enchondroma, Giant cell tumor

Epidemiology

Incidence per 100.000 [g5i][sk6][gk6][d7u]

Approach

• Blood test: blood count, alkaline phosphatase, and lactate dehydrogenase

• X-ray

• MRI

• Biopsy

• CT scan of the lungs

• PET-CT scan

Treatment

1. Chemotherapy: [gk6]

   • Neoadjuvant (preoperative) --> Tumor shrinkage --> Facilitate surgical removal

   • Provide an important risk parameter

2. Radiotherapy: Osteosarcomas are not particularly responsive to radiotherapy

3. Surgery is the only option for definitive tumor removal [g5i]

   • Wide local excision

   • Limb-sparing surgery with allograft bone replacement or metallic prosthetics

   • Amputation

   • Rotationplasty

4. Samarium: A radioactive drug that targets areas where bone cells are growing

5. Targeted therapy: Drugs that block the action of specific enzymes, proteins, or other molecules involved in the growth of benign or malignant tumor cells

   • Kinase inhibitor

   • Mammalian target of rapamycin (mTOR) inhibitor [ree]

Differential diagnoses

Arthritis, Ewing sarcoma, Fracture, Langerhans cell histiocytosis, Lymphoma, Osteoblastoma, Osteoid osteoma, Osteomyelitis, Osteoperiostitis, Spinal disc herniation