Ewing Sarcoma in Children
Ewing Sarcoma in Pediatric Age
Ewing sarcoma is a rare, aggressive malignancy primarily affecting children and young adults. It belongs to the Ewing sarcoma family of tumors (EFTs), which includes Ewing sarcoma of bone, extraosseous Ewing sarcoma, primitive neuroectodermal tumor (PNET), and Askin tumor (Ewing sarcoma of the chest wall).
- Second most common primary bone malignancy in children and adolescents
- Typically occurs in long bones, pelvis, and chest wall
- Characterized by small, round, blue cells on histology
- Associated with a specific chromosomal translocation: t(11;22)(q24;q12)
Epidemiology
- Incidence: 2.9 cases per million children
- Peak incidence: 10-20 years of age
- Slight male predominance (1.5:1 male to female ratio)
- More common in Caucasians; rare in African and Asian populations
- No clear environmental or genetic predisposing factors identified
Pathophysiology
- Arises from primitive neuroectodermal cells or mesenchymal stem cells
- Characterized by the EWSR1-FLI1 fusion gene (85% of cases)
- Other fusion partners include ERG, ETV1, ETV4, and FEV
- Fusion proteins act as aberrant transcription factors, leading to:
- Increased cell proliferation
- Decreased apoptosis
- Altered differentiation
- Enhanced angiogenesis
Clinical Presentation
- Pain and swelling at the tumor site (most common symptoms)
- Systemic symptoms: fever, weight loss, fatigue
- Pathological fractures (10-15% of cases)
- Neurological symptoms if spinal involvement
- Common primary sites:
- Axial skeleton: pelvis, ribs, vertebrae
- Appendicular skeleton: femur, tibia, fibula, humerus
- Soft tissue (extraosseous Ewing sarcoma)
Diagnosis
- Imaging studies:
- X-ray: "onion-skin" appearance, periosteal reaction
- MRI: extent of tumor and soft tissue involvement
- CT: lung metastases
- Bone scan: additional bone lesions
- PET-CT: metabolic activity and staging
- Biopsy: essential for definitive diagnosis
- Histology: small, round, blue cells
- Immunohistochemistry: CD99 positive, FLI1 positive
- Molecular testing: EWSR1 rearrangement (FISH or RT-PCR)
- Laboratory tests:
- Elevated LDH, ESR, and CRP
- Anemia
- Leukocytosis
Treatment
Multimodal approach including:
- Neoadjuvant chemotherapy:
- Vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC/IE)
- Duration: 12-18 weeks
- Local control:
- Surgery: wide resection when possible
- Radiation therapy: for unresectable tumors or positive margins
- Adjuvant chemotherapy:
- Continuation of VDC/IE regimen
- Total duration of chemotherapy: 8-12 months
- Management of metastatic disease:
- Intensified chemotherapy regimens
- Consideration of high-dose chemotherapy with stem cell rescue
- Local control of metastatic sites (surgery or radiation)
- Emerging therapies:
- Targeted therapies: IGF-1R inhibitors, PARP inhibitors
- Immunotherapy: GD2-targeted therapies, checkpoint inhibitors
Prognosis
- 5-year overall survival:
- Localized disease: 70-80%
- Metastatic disease: 30-40%
- Prognostic factors:
- Presence of metastases at diagnosis (most important)
- Tumor size and location
- Age at diagnosis (younger age associated with better outcomes)
- Response to neoadjuvant chemotherapy
- Surgical margins
- Long-term sequelae:
- Growth abnormalities
- Limb-length discrepancies
- Secondary malignancies
- Cardiotoxicity from anthracyclines
- Infertility
Ewing Sarcoma in Pediatric Age
- What is the characteristic genetic alteration in Ewing sarcoma?
EWSR1-FLI1 fusion (t(11;22) translocation) - What is the peak age of incidence for Ewing sarcoma?
10-20 years old - Which ethnic group has the highest incidence of Ewing sarcoma?
Caucasians - What is the most common primary site for Ewing sarcoma?
Pelvis and long bones of the lower extremities - Which imaging modality is considered the gold standard for local staging of Ewing sarcoma?
MRI - What is the characteristic histological appearance of Ewing sarcoma cells?
Small round blue cells - Which chemotherapy drugs are commonly used in the treatment of Ewing sarcoma?
Vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide - What is the overall survival rate for localized Ewing sarcoma?
70-80% - Which presenting symptom is most common in Ewing sarcoma?
Pain and swelling at the tumor site - What is the name of the staging system used for Ewing sarcoma?
TNM staging system - Which imaging modality is used for detecting bone metastases in Ewing sarcoma?
Technetium-99m bone scan - What is the most common site of metastasis in Ewing sarcoma?
Lungs - Which immunohistochemical marker is positive in Ewing sarcoma?
CD99 - What is the typical duration of chemotherapy for Ewing sarcoma?
10-12 months - Which prognostic factor is associated with poor outcome in Ewing sarcoma?
Presence of metastases at diagnosis - What is the role of radiation therapy in the treatment of Ewing sarcoma?
Used for local control, especially in unresectable tumors - Which molecular pathway is targeted by newer treatments for Ewing sarcoma?
PARP inhibition - What is the name of the cooperative group that conducts most Ewing sarcoma clinical trials in North America?
Children's Oncology Group (COG) - Which imaging modality is used to assess treatment response in Ewing sarcoma?
CT or MRI - What is the most common extraosseous primary site for Ewing sarcoma?
Soft tissues of the trunk - Which laboratory finding is often elevated in Ewing sarcoma?
Lactate dehydrogenase (LDH) - What is the name of the phenomenon where Ewing sarcoma cells form rosette-like structures?
Homer Wright rosettes - Which gene is the most common fusion partner with EWSR1 in Ewing sarcoma?
FLI1 - What is the recommended follow-up imaging for Ewing sarcoma survivors?
CT chest and imaging of primary site - Which late effect is associated with anthracycline chemotherapy in Ewing sarcoma treatment?
Cardiomyopathy - What is the name of the surgical approach that aims to preserve function in limb Ewing sarcoma?
Limb-salvage surgery - Which molecular test is used to detect EWSR1 rearrangements in Ewing sarcoma?
FISH or RT-PCR - What is the most common second malignancy in Ewing sarcoma survivors?
Acute myeloid leukemia - Which growth factor receptor is often overexpressed in Ewing sarcoma?
Insulin-like growth factor 1 receptor (IGF1R) - What is the name of the Ewing sarcoma-like tumor that lacks EWSR1 rearrangement?
Ewing-like sarcoma or round cell sarcoma
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.
