Overview
Definition:
Osteosarcoma is a malignant mesenchymal tumor characterized by the production of osteoid by the malignant cells
Ewing sarcoma is a highly malignant small round blue cell tumor of bone and soft tissue, typically arising in the diaphysis of long bones or the axial skeleton.
Epidemiology:
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, with a peak incidence in the second decade of life
Ewing sarcoma is the second most common primary bone cancer in children, typically occurring in children aged 10-20 years
Geographic variations exist, with higher incidence in North America and Europe
Both are rare overall, comprising <1% of all childhood cancers.
Clinical Significance:
Accurate differentiation between osteosarcoma and Ewing sarcoma is crucial for appropriate management, as treatment protocols, prognosis, and response to therapy differ significantly
Misdiagnosis can lead to suboptimal treatment and adverse outcomes for pediatric patients.
Clinical Presentation
Symptoms:
Pain in the affected bone, often worse at night and exacerbated by activity
Swelling or a palpable mass over the affected area
Limp or difficulty using the limb if the leg is affected
Pathological fracture occurring with minimal or no trauma
Systemic symptoms like fever, weight loss, and fatigue are more common with Ewing sarcoma, especially if metastatic.
Signs:
Localized tenderness and warmth over the tumor site
A palpable mass that may be firm and fixed
Restricted range of motion in adjacent joints
Ecchymosis or erythema overlying the mass in some cases
Systemic signs of illness may be present, particularly with widespread disease.
Diagnostic Criteria:
Diagnosis relies on a combination of clinical presentation, imaging studies, and histopathological examination
Histological confirmation is mandatory
No specific diagnostic criteria exist beyond the definitive histopathological diagnosis, but a high index of suspicion is warranted in children with bone pain and swelling.
Diagnostic Approach
History Taking:
Detailed history of bone pain (duration, character, nocturnal exacerbation, relation to activity)
History of trauma (though often incidental)
Presence of swelling or mass
Fever, weight loss, fatigue
Past medical history, including previous radiation therapy or chemotherapy
Family history of cancer.
Physical Examination:
Palpation of the affected bone for tenderness, warmth, and mass
Assessment of the extent of swelling and any palpable lymphadenopathy
Evaluation of range of motion of adjacent joints
Examination for distant metastases (e.g., lungs, liver)
Systemic review for constitutional symptoms.
Investigations:
Plain radiographs: often show a destructive bone lesion with periosteal reaction (Codman's triangle in osteosarcoma, sunburst appearance in Ewing sarcoma) and a soft tissue mass
MRI: The modality of choice for local staging, assessing tumor extent, neurovascular involvement, and intra-medullary spread
CT scan: Useful for assessing cortical breach and for pulmonary staging (detecting lung metastases)
Bone scan (Technetium-99m): Evaluates for skip lesions and skeletal metastases
Laboratory tests: Elevated alkaline phosphatase (AP) is common in osteosarcoma but not specific
Complete blood count (CBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) may be elevated in Ewing sarcoma
Serum lactate dehydrogenase (LDH) can be elevated in Ewing sarcoma and is a poor prognostic indicator.
Differential Diagnosis:
Benign bone lesions (e.g., osteochondroma, enchondroma, osteoid osteoma)
Other malignant bone tumors (e.g., chondrosarcoma, fibrosarcoma)
Metastatic tumors to bone (e.g., neuroblastoma, Wilms tumor)
Osteomyelitis (especially chronic)
Hematological malignancies involving bone
Soft tissue sarcomas.
Management
Initial Management:
Prompt referral to a pediatric oncologist or orthopedic oncologist
Imaging and biopsy for definitive diagnosis
Staging of the disease to determine extent and presence of metastases.
Medical Management:
Chemotherapy is the cornerstone of treatment for both
Osteosarcoma: Neoadjuvant chemotherapy (e.g., high-dose methotrexate, doxorubicin, cisplatin) followed by surgery, and then adjuvant chemotherapy
Ewing sarcoma: Neoadjuvant chemotherapy (e.g., vincristine, dactinomycin, cyclophosphamide, doxorubicin, etoposide - VDC/IE regimen) followed by surgery or radiation, and then adjuvant chemotherapy.
Surgical Management:
Osteosarcoma: Limb-sparing surgery is preferred when feasible, aiming for complete tumor resection with wide margins
Amputation may be necessary for unresectable tumors or when limb salvage is not oncologically sound
Reconstruction is performed using endoprostheses, allografts, or autografts
Ewing sarcoma: Surgical resection with adequate margins is often performed, especially for localized disease
Radiation therapy is a significant component of treatment for Ewing sarcoma, particularly for tumors in areas difficult to resect surgically (e.g., pelvis, axial skeleton) or when margins are close/positive after surgery.
Supportive Care:
Pain management: analgesics, including opioids as needed
Nutritional support: adequate caloric and protein intake
Blood product support: transfusions for anemia or thrombocytopenia
Management of chemotherapy side effects: antiemetics, growth factors (G-CSF), infection prophylaxis
Psychosocial support for the patient and family.
Complications
Early Complications:
Infection (surgical site infection, sepsis)
Bleeding
Wound dehiscence
Metastasis to lungs or bone
Severe toxicity from chemotherapy (e.g., myelosuppression, mucositis, cardiotoxicity, nephrotoxicity).
Late Complications:
Recurrence of the tumor (local or distant)
Limb length discrepancy or functional impairment after limb salvage surgery
Osteoarthritis of adjacent joints
Radiation-induced sarcomas or secondary malignancies
Infertility due to chemotherapy/radiation
Growth disturbances
Psychological distress.
Prevention Strategies:
Meticulous surgical technique to minimize infection and bleeding
Aggressive pulmonary staging to detect and manage metastases early
Prophylactic antiemetics and G-CSF for chemotherapy
Careful monitoring for tumor recurrence and second malignancies
Genetic counseling and fertility preservation options.
Prognosis
Factors Affecting Prognosis:
For osteosarcoma: tumor site, size, presence of metastasis at diagnosis, response to neoadjuvant chemotherapy (histological necrosis), and achievement of negative surgical margins
For Ewing sarcoma: presence of metastasis at diagnosis, tumor site, tumor size, serum LDH levels, and response to initial therapy
Genetic factors and specific molecular markers also play a role.
Outcomes:
With current multimodal therapy, the 5-year survival rate for localized osteosarcoma is approximately 60-70%
For localized Ewing sarcoma, survival rates can be around 70-80%
Metastatic disease significantly reduces survival for both
Continuous research is improving outcomes.
Follow Up:
Regular clinical examinations, serial chest X-rays and CT scans for pulmonary surveillance, and bone scans as indicated for at least 5-10 years
Monitoring for late effects of treatment, including growth and development, skeletal integrity, cardiovascular health, and endocrine function.
Key Points
Exam Focus:
Osteosarcoma: Osteoid production by malignant cells, common in metaphysis of long bones, sunburst periosteal reaction, Codman triangle
Ewing Sarcoma: Small round blue cell tumor, diaphysis of long bones or axial skeleton, onion skin periosteal reaction, often associated with systemic symptoms, t(11;22) translocation.
Clinical Pearls:
Always consider primary bone tumors in a child with persistent bone pain and swelling, especially if worsening at night
Plain X-ray is the first imaging modality, but MRI is crucial for local staging
Histopathology is definitive
Multidisciplinary team approach is essential for optimal management.
Common Mistakes:
Attributing bone pain solely to trauma or growing pains without further investigation
Delays in referral to specialist centers
Inadequate biopsy technique, leading to sampling error
Underestimating the importance of staging investigations, especially pulmonary CT
Misinterpreting radiographic findings without considering the clinical context and histopathology.