Osteosarcoma

Aka: Osteosarcoma, Osteogenic Sarcoma, Bone Sarcoma

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II. Epidemiology

  1. Bone Sarcoma is rare
    1. Incidence: 2500 U.S. cases diagnosed per year overall
    2. Of these, 1200 cases of Osteosarcoma are diagnosed
  2. Osteosarcoma is most common Bone Sarcoma and the most common Bone Cancer
    1. Third most common childhood malignancy
  3. Ages affected: 5-30 years (most common ages 10-20)
    1. Median Incidence age 12 years in girls and age 16 years in boys
    2. Rare after age 60 years
  4. Gender
    1. More common in males
  5. Race
    1. More common in black patients

III. Risk Factors

  1. Genetic factors
    1. Li-Fraumeni Syndrome (p53 oncogene mutation)
    2. Retinoblastoma (Rb oncogene mutation)
    3. Rothmund-Thomson Syndrome (Autosomal Recessive)
  2. Other factors
    1. Radiation Therapy (precedes Osteosarcoma by 10-20 years)
    2. Orthopedic surgery with implanted metal prosthesis
    3. Paget Disease

IV. Pathophysiology

  1. High-grade mesenchymal tumor
    1. Primitive mesenchymal cells differentiate into Osteoblasts
    2. Osteoblasts generate malignant osteoid matrix
  2. Most common sites (60% of cases) of involvement
    1. Long bone metaphysis
      1. Distal femur
      2. Proximal tibia
      3. Proximal Humerus
    2. Other sites
      1. Pelvis
      2. Skull
  3. Most common sites of metastasis
    1. Skip lesions
      1. Regional metastases form via satellite growth
      2. May be transarticular across a joint or intraosseous along the same bone
    2. Systemic metastases
      1. Lungs (most common)
      2. Distant bone (occurs after lung metastases)
  4. Growth
    1. Grows outward radially forming ball-like mass
    2. Metaphysis contains Growth Plate and Osteosarcomas are most common when bone growth is rapid
    3. Reactive Zone (Pseudocapsule composed of Muscle)
      1. Forms when Tumor extends beyond bone cortex
      2. Compresses surrounding Muscles
      3. Muscle appears as pseudocapsule to tumor
    4. Satellites (Tumor extension beyond pseudocapsule)
      1. Small tumor Nodules form outside pseudocapsule
      2. Microextension of tumor (satellites)

V. Symptoms

  1. Dull aching unilateral bone pain for several months
    1. Patient often presents for sudden worsening
    2. Referred pain is common in children
  2. Night pain may awaken patient from sleep
    1. Distinguishing feature from benign causes
  3. May be misdiagnosed associated with minor injury
    1. Growing Pains (e.g. Osgood Schlatter)
    2. Recent Knee Injury or strain
  4. Uncommon features
    1. Fever
    2. Night Sweats
    3. Weight loss
    4. Lymphadenopathy (think Osteomyelitis if present)

VI. Signs

  1. Local tenderness, swelling, mass or deformity
  2. Patient limps
  3. Muscle atrophy
  4. Decreased joint range of motion
  5. Pathologic Fracture

VII. Differential diagnosis

  1. Ewing's Sarcoma
  2. Osteomyelitis
  3. Osteoblastoma
  4. Giant Cell Tumor
  5. Aneurysmal bone cyst
  6. Fibrous dysplasia

VIII. Imaging

  1. Bone XRay
    1. Sunburst appearance (radiating calcifications)
    2. Dense sclerosis (small, irregular cloud-like densities) most commonly at metaphysis
    3. Lytic lesions (30% of cases)
    4. Pathologic Fractures
  2. Bone MRI
    1. Defines tumor involvement
      1. Intraosseous and extraosseous changes
      2. Soft tissue extension (75% of cases)
      3. Skip lesions
      4. Neurovascular involvement
    2. Used preoperatively
      1. Establishes surgical margins (2-3 cm from tumor)
      2. Establishes resectability
  3. Bone CT with contrast
    1. Preferred over MRI if significant edema and necrosis
    2. Defines neurovascular structures via IV contrast
  4. Other measures used in defining tumor involvement
    1. Chest XRay
      1. Up to 20% of patients present with lung metastases
    2. Bone scintigraphy
    3. Thallium scintigraphy
    4. Angiography

IX. Staging (Enneking system)

  1. Stage I: Low-grade tumor
  2. Stage IA: Intracompartmental
  3. Stage IB: Extracompartmental
  4. Stage II: High grade tumor
  5. Stage IIA: Intracompartmental
  6. Stage IIB: Extracompartmental
  7. Stage III: Metastatic disease from either grade
  8. Enneking (1980) Clin Orthop 153:106-20 [PubMed]

X. Monitoring

  1. Timing
    1. First 2 years after treatment: Every 3 months
    2. Two to 5 years after treatment: Every 6 months
    3. Five or more years after treatment: Annual
  2. Protocol
    1. Serial Physical exams
      1. Palpate extremity for masses
      2. Assess for prosthetic failure or Infection
    2. Serial XRay of involved limb
    3. Serial CT Chest
      1. Baseline, at time of diagnosis
      2. Repeat every 6 months to 2 years
  3. Additional testing
    1. Bone scan annually for first 2 years

XI. Management

  1. Surgery (preceded and followed by Chemotherapy)
    1. Limb salvage in most cases
      1. Amputation in some cases of large tumor, vital structure risk, tumor progression or poor response
    2. Tumor resection with clear margins and limb reconstruction
  2. Chemotherapy
    1. Phases
      1. Neoadjuvant (pre-operative Chemotherapy)
      2. Adjuvant (post-operative Chemotherapy)
    2. Common Agents used
      1. Cisplatin
      2. Doxorubicin (Adriamycin)
      3. Methotrexate (high dose)
      4. Additional agents may be used in combination (e.g. Etoposide, Isosfamide)

XII. Prognosis: Survival

  1. Eligible for limb sparing surgery in U.S.: 90-95%
    1. Contrast with 100% amputation rate before 1970
  2. Long-term survival with localized disease: 60-80%
    1. Contrast with 80% mortality rate before 1970

XIII. Prognosis: Predictive factors (same as for Ewing's Sarcoma)

  1. Positive prognostic factors
    1. Localized extremity disease
    2. Clear margins on surgical resection
    3. Tumor necrosis response >90%
  2. Negative prognostic factors
    1. Incomplete surgical resection
    2. Older patient age at onset
    3. Poor Chemotherapy response
    4. Metastases present
    5. Axial skeleton primary tumors
    6. Tumor >8 cm in size

XIV. References

  1. Abeloff (2000) Clinical Oncology, Churchill, p. 2170-97
  2. Canale (1998) Campbell's Orthopaedics, Mosby, p. 715-7
  3. Ferguson (2018) Am Fam Physician 98(4): 205-13 [PubMed]
  4. Wittig (2002) Am Fam Physician 65(6): 1123-32 [PubMed]

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