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Osteosarcoma in Pediatric Age

Osteosarcoma in Pediatric Age

Osteosarcoma is the most common primary bone malignancy in children and adolescents. It is a high-grade neoplasm in which malignant cells produce osteoid (immature bone).

Key Points:

  • Most common primary malignant bone tumor in children and adolescents
  • Typically occurs in the metaphyseal regions of long bones
  • Peak incidence during adolescent growth spurt
  • Requires a multimodal treatment approach
  • Survival rates have improved significantly with modern treatment protocols

Epidemiology

Osteosarcoma primarily affects children, adolescents, and young adults:

  • Incidence: 4.4 cases per million per year in children aged 0-14 years
  • Peak incidence: 15-19 years of age
  • Slight male predominance (1.4:1)
  • Second incidence peak in adults over 60 years (often associated with Paget's disease or prior radiation)

Risk Factors:

  • Rapid bone growth (adolescent growth spurt)
  • Genetic predisposition: Li-Fraumeni syndrome, hereditary retinoblastoma
  • Previous radiation exposure
  • Paget's disease of bone (in older adults)
  • Chronic osteomyelitis

Pathogenesis

The pathogenesis of osteosarcoma involves complex genetic and molecular alterations:

Key Genetic Abnormalities:

  • RB1 gene mutations (Retinoblastoma gene)
  • TP53 gene mutations
  • RECQL4 gene mutations (Rothmund-Thomson syndrome)
  • Chromosomal aneuploidy and complex karyotypes

Molecular Pathways:

  • Dysregulation of cell cycle control
  • Alterations in DNA repair mechanisms
  • Aberrant activation of growth factor signaling pathways (e.g., IGF-1R, VEGF)

These genetic and molecular changes lead to uncontrolled proliferation of osteoblastic cells and production of abnormal osteoid.

Classification

Osteosarcoma is classified based on histological features and location:

Histological Subtypes:

  1. Conventional Osteosarcoma (80-90% of cases)
    • Osteoblastic
    • Chondroblastic
    • Fibroblastic
  2. Telangiectatic Osteosarcoma
  3. Small Cell Osteosarcoma
  4. Low-grade Central Osteosarcoma
  5. Parosteal Osteosarcoma
  6. Periosteal Osteosarcoma

Location:

  • Intramedullary (central) - most common
  • Surface (peripheral)
  • Extraskeletal (rare)

Clinical Presentation

The clinical presentation of osteosarcoma can vary, but common symptoms include:

Symptoms:

  • Pain: Initially intermittent, often worse at night, progressively becomes constant
  • Swelling or mass: May be warm and tender
  • Decreased joint mobility
  • Pathological fracture (10-15% of cases)

Common Primary Sites:

  • Distal femur (40%)
  • Proximal tibia (20%)
  • Proximal humerus (10%)
  • Other sites: Pelvis, jaw, vertebrae

Note: Symptoms are often attributed to sports injuries or growing pains, leading to potential delays in diagnosis.

Diagnosis

Diagnosis of osteosarcoma involves a combination of imaging studies, biopsy, and laboratory tests:

Imaging Studies:

  • Plain Radiography: Initial imaging modality
    • Characteristic "sunburst" pattern
    • Codman's triangle (periosteal reaction)
  • MRI: For local staging and soft tissue extension
  • CT: For evaluation of pulmonary metastases
  • Bone Scan: To assess for skip metastases and distant bone involvement
  • PET-CT: For initial staging and response assessment

Biopsy:

  • Core needle biopsy: Preferred method
  • Open biopsy: If core biopsy is non-diagnostic

Laboratory Tests:

  • Elevated alkaline phosphatase and lactate dehydrogenase (LDH)
  • Complete blood count, renal and liver function tests

Histopathology:

  • Presence of malignant mesenchymal cells producing osteoid
  • Immunohistochemistry: SATB2, osteocalcin, osteonectin

Staging

Osteosarcoma is typically staged using the Enneking system and the AJCC (American Joint Committee on Cancer) system:

Enneking System:

  • Stage I: Low-grade, no metastases
  • Stage II: High-grade, no metastases
  • Stage III: Any grade, with metastases

AJCC System (8th edition):

  • Stage IA: G1 or GX, T1, N0, M0
  • Stage IB: G1 or GX, T2 or T3, N0, M0
  • Stage IIA: G2 or G3, T1, N0, M0
  • Stage IIB: G2 or G3, T2, N0, M0
  • Stage III: G2 or G3, T3, N0, M0
  • Stage IVA: Any G, Any T, N0, M1a (lung metastases)
  • Stage IVB: Any G, Any T, N1, Any M or M1b (other distant metastases)

Note: Most pediatric osteosarcomas are high-grade (G2 or G3) at diagnosis.

Treatment

Treatment of osteosarcoma requires a multimodal approach:

1. Neoadjuvant Chemotherapy:

  • Standard regimen: MAP (Methotrexate, Doxorubicin, Cisplatin)
  • Duration: Typically 10-12 weeks
  • Goals: Tumor necrosis, treatment of micrometastases

2. Surgery:

  • Limb-salvage surgery (preferred when possible)
  • Amputation (if limb-salvage not feasible)
  • Rotationplasty (for distal femur or proximal tibia tumors)

3. Adjuvant Chemotherapy:

  • Continuation of MAP regimen
  • Total duration of chemotherapy: 6-8 months
  • Adjustments based on histological response to neoadjuvant therapy

4. Radiation Therapy:

  • Not routinely used due to osteosarcoma's relative radioresistance
  • May be considered for unresectable tumors or positive margins

5. Novel Therapies:

  • Immunotherapy: Mifamurtide (muramyl tripeptide)
  • Targeted therapies: IGF-1R inhibitors, mTOR inhibitors
  • Radionuclide therapy: Samarium-153-EDTMP

Prognosis

Prognosis for osteosarcoma has improved significantly with modern treatment protocols:

Prognostic Factors:

  • Presence of metastases at diagnosis (most important factor)
  • Tumor size and location
  • Surgical margins
  • Histological response to neoadjuvant chemotherapy
  • Serum LDH and alkaline phosphatase levels

Survival Rates:

  • Localized disease: 60-70% 5-year overall survival
  • Metastatic disease: 20-30% 5-year overall survival
  • Recurrent disease: Poor prognosis, <20% long-term survival

Long-term Follow-up:

  • Regular imaging to monitor for recurrence and metastases
  • Screening for late effects of therapy (e.g., cardiotoxicity, hearing loss, infertility)
  • Monitoring for secondary malignancies

Ongoing research aims to improve outcomes for patients with poor prognostic factors and those with metastatic or recurrent disease.



Osteosarcoma in Pediatric Age
  1. What is the most common primary malignant bone tumor in children and adolescents?
    Osteosarcoma
  2. What is the peak age of incidence for osteosarcoma?
    10-20 years old
  3. Which genetic syndrome is associated with an increased risk of osteosarcoma?
    Li-Fraumeni syndrome
  4. What is the most common primary site for osteosarcoma?
    Metaphysis of long bones (distal femur, proximal tibia, proximal humerus)
  5. Which imaging modality is considered the gold standard for local staging of osteosarcoma?
    MRI
  6. What is the characteristic histological feature of osteosarcoma?
    Production of osteoid by malignant cells
  7. Which chemotherapy drugs are commonly used in the treatment of osteosarcoma?
    Methotrexate, doxorubicin, and cisplatin (MAP regimen)
  8. What is the overall survival rate for localized osteosarcoma?
    70-75%
  9. Which presenting symptom is most common in osteosarcoma?
    Pain and swelling at the tumor site
  10. What is the name of the staging system used for osteosarcoma?
    Enneking staging system
  11. Which imaging modality is used for detecting bone metastases in osteosarcoma?
    Technetium-99m bone scan
  12. What is the most common site of metastasis in osteosarcoma?
    Lungs
  13. Which laboratory test is often elevated in osteosarcoma?
    Alkaline phosphatase
  14. What is the typical duration of chemotherapy for osteosarcoma?
    6-8 months
  15. Which prognostic factor is associated with better outcome in osteosarcoma?
    Good histologic response to neoadjuvant chemotherapy
  16. What is the role of radiation therapy in the treatment of osteosarcoma?
    Limited role, used mainly for palliation or in unresectable tumors
  17. Which molecular pathway is targeted by newer treatments for osteosarcoma?
    mTOR pathway
  18. What is the name of the cooperative group that conducts most osteosarcoma clinical trials in North America?
    Children's Oncology Group (COG)
  19. Which imaging modality is used to assess treatment response in osteosarcoma?
    CT or MRI
  20. What is the most common histological subtype of osteosarcoma?
    Conventional (osteoblastic) osteosarcoma
  21. Which radiographic finding is characteristic of osteosarcoma?
    Codman's triangle
  22. What is the name of the phenomenon where osteosarcoma cells form a "sunburst" pattern on imaging?
    Sunburst periosteal reaction
  23. Which gene is commonly mutated in sporadic osteosarcoma?
    RB1 (Retinoblastoma) gene
  24. What is the recommended follow-up imaging for osteosarcoma survivors?
    Chest CT and imaging of primary site
  25. Which late effect is associated with cisplatin chemotherapy in osteosarcoma treatment?
    Hearing loss
  26. What is the name of the surgical approach that aims to preserve function in limb osteosarcoma?
    Limb-salvage surgery
  27. Which molecular test is used to detect TP53 mutations in osteosarcoma?
    Next-generation sequencing
  28. What is the most common second malignancy in osteosarcoma survivors?
    Secondary sarcomas
  29. Which growth factor receptor is often overexpressed in osteosarcoma?
    Insulin-like growth factor 1 receptor (IGF1R)
  30. What is the name of the osteosarcoma subtype that occurs in older adults?
    Secondary osteosarcoma


Disclaimer

The notes provided on Pediatime are generated from online resources and AI sources and have been carefully checked for accuracy. However, these notes are not intended to replace standard textbooks. They are designed to serve as a quick review and revision tool for medical students and professionals, and to aid in theory exam preparation. For comprehensive learning, please refer to recommended textbooks and guidelines.





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