Despite its rarity—affecting only about 225 young people in the U.S. each year—Ewing Sarcoma is a formidable and aggressive cancer that demands our urgent attention.
Key Takeaways
- Ewing sarcoma represents about 1% to 2% of all childhood cancers
- Approximately 225 children and adolescents are diagnosed with Ewing sarcoma each year in the United States
- The incidence rate of Ewing sarcoma is 2.9 cases per million children and adolescents aged 0-19 years worldwide
- More common in males with 1.4:1 ratio
- Peak incidence ages 10-20 years (75% of cases)
- Predominantly affects Caucasians (incidence 3x higher than African Americans)
- Pain at tumor site is the most common initial symptom (80-90%)
- Swelling or mass at site in 70% of cases
- Fever present in 20-30% without infection
- Biopsy confirms small round blue cell tumor
- EWSR1-FLI1 fusion detected by FISH in 95%
- MRI shows bone marrow involvement in 90%
- Multi-agent chemotherapy standard (vincristine, doxorubicin, cyclophosphamide, etc.)
- 5-year survival for localized disease 70-80%
- Metastatic disease 5-year survival 20-30%
Ewing sarcoma is a rare childhood cancer with about 200 US cases diagnosed each year.
Demographics and Risk Factors
- More common in males with 1.4:1 ratio
- Peak incidence ages 10-20 years (75% of cases)
- Predominantly affects Caucasians (incidence 3x higher than African Americans)
- Mean age at diagnosis 14.8 years
- Male to female ratio 1.3:1 to 1.5:1
- Extremely rare in African descent populations
- 70% of patients under 20 years old
- Higher incidence in adolescents than children under 10
- Rare in Asians (0.3 per million)
- No strong familial predisposition
- Associated with taller stature in some studies
- Genetic translocation t(11;22) in 85% of cases
- EWSR1-FLI1 fusion in 90-95% of Ewing sarcomas
- No known environmental risk factors definitively
- Possible weak link to paternal radiation exposure
- Higher in Europeans due to genetic susceptibility
- Median age 15 years, 60% male
- Rare before puberty, peaks post-puberty
- 5% of cases in adults over 40
- No association with smoking or alcohol
- Linked to germline TP53 mutations in some
- Most common in white non-Hispanics (2.3 per million)
- 25% familial aggregation rare
Demographics and Risk Factors Interpretation
This cancer seems to have a cruel and specific type: it has a clear adolescent bias, a puzzling racial disparity, and a definite male preference, making it an unwelcome and targeted intruder in the lives of mostly teenage boys of European ancestry.
Diagnosis and Pathology
- Biopsy confirms small round blue cell tumor
- EWSR1-FLI1 fusion detected by FISH in 95%
- MRI shows bone marrow involvement in 90%
- CT-guided biopsy diagnostic in 98%
- PET-CT for staging detects metastases in 80%
- CD99 positivity in 95-100% on immunohistochemistry
- t(11;22)(q24;q12) in 85-90% by cytogenetics
- Bone scan shows uptake in primary and mets (sensitive 90%)
- Plain X-ray: permeative destruction with periosteal reaction (onion skin) in 70%
- LDH >180 U/L adverse prognostic factor
- Electron microscopy shows glycogen rosettes
- Whole body MRI for staging superior to CT in some studies
- Micrometastases detected by PCR in 20% bone marrow
- FLi-1 nuclear positivity confirmatory
- Staging: 20-25% metastatic at diagnosis (ENCCS group IV)
- Tumor volume >200 mL poor prognostic
- RT-PCR for EWS-FLI1 transcript diagnostic
- Axial skeleton involvement in 50%
- H3K27 acetylation profiling distinguishes from mimics
- Bilateral bone marrow biopsies negative in localized disease 75%
- Neoadjuvant chemotherapy response assessed by necrosis >90% good
Diagnosis and Pathology Interpretation
While nearly all cases light up with CD99, the critical EWSR1-FLI1 fusion—the disease's molecular fingerprint—is found in 95% of patients, and when combined with a CT-guided biopsy, this devastating bone cancer is identified with near certainty in 98% of cases.
Incidence and Prevalence
- Ewing sarcoma represents about 1% to 2% of all childhood cancers
- Approximately 225 children and adolescents are diagnosed with Ewing sarcoma each year in the United States
- The incidence rate of Ewing sarcoma is 2.9 cases per million children and adolescents aged 0-19 years worldwide
- Ewing sarcoma has an annual incidence of 1.4 per million in the US population under 20 years
- In Europe, the incidence of Ewing sarcoma is around 3 per million children under 15 years
- Ewing sarcoma comprises 6-7% of all primary malignant bone tumors
- Global incidence shows higher rates in European populations at 2.9 per million
- In the US, about 200-250 new cases annually among people under 20
- Incidence peaks between ages 10-14 years with 4.5 cases per million
- Rare in adults over 40, with less than 5% of cases
- Ewing sarcoma incidence is lower in African and Asian populations
- Accounts for 10-20% of primary bone sarcomas in children
- Median age at diagnosis is 15 years
- Annual incidence in adolescents 15-19 is 2.9 per million
- Ewing sarcoma is the second most common primary bone cancer in pediatric patients after osteosarcoma
- Prevalence is low due to poor survival, estimated at 500-1000 survivors in US
- Incidence rate stable over past decades at ~1 per million under 20
- Higher in Hispanics at 3.3 per million vs 2.1 in non-Hispanics
- Represents 200 cases yearly in Europe for under 20s
- 85% of cases diagnosed before age 20
- Incidence in females slightly lower than males (1.4 vs 1.5 per million)
- Rare under age 5, with <10% of cases
- Ewing sarcoma more common in rural areas per some studies
- Lifetime risk ~1 in 1.3 million
- Peaks in second decade of life
- 25% of cases in soft tissue (extraosseous)
- Incidence declined slightly from 1973-2012
- Most common in pelvis (25%), femur (20%)
- Affects long bones in 40-50% of cases
- Global variation highest in Europe/North America
Incidence and Prevalence Interpretation
While statistically rare as childhood cancers go, Ewing sarcoma is a formidable foe, striking a predictable few hundred adolescents each year in the U.S. with a particular cruelty that peaks in the bones of teenagers.
Symptoms and Clinical Features
- Pain at tumor site is the most common initial symptom (80-90%)
- Swelling or mass at site in 70% of cases
- Fever present in 20-30% without infection
- Weight loss in 30% at diagnosis
- Fatigue common due to systemic effects
- Limping or pathologic fracture in lower extremity cases (40%)
- Back pain if spinal involvement (10-15%)
- Chest pain or shortness of breath in chest wall tumors
- Elevated LDH in 30-40% correlating with poor prognosis
- Anemia in 50% at presentation
- Pelvic tumors present with hip pain (25% of sites)
- Night pain wakes patient in 60%
- Systemic symptoms like fever mimic osteomyelitis (25%)
- Mass palpable in 60-70% of extremity cases
- Neurological deficits if cauda equina involved (rare)
- 20-25% have metastases at diagnosis, often lung
- Rib tumors cause respiratory symptoms (5-10%)
- Leukocytosis in 45% without infection
- Duration of symptoms before diagnosis averages 3-6 months
- Scapula involvement leads to shoulder pain (7%)
Symptoms and Clinical Features Interpretation
If the classic story of Ewing Sarcoma were a grim novel, its opening chapter would be titled "A Night Pains and Swelling," where the protagonist endures months of ambiguous agony before the plot twist of a poor prognosis—often written in elevated LDH levels—reveals itself far too late.
Treatment and Prognosis
- Multi-agent chemotherapy standard (vincristine, doxorubicin, cyclophosphamide, etc.)
- 5-year survival for localized disease 70-80%
- Metastatic disease 5-year survival 20-30%
- Local control with surgery + radiation 90%
- Overall survival improved from 50% to 75% with multi-modal therapy
- Radiation dose 45-60 Gy for unresectable tumors
- Relapse-free survival 60-70% at 5 years localized
- Lung metastases respond best to chemo (40% long-term survival)
- Poor response to chemo (<10% necrosis) predicts 20% survival
- Ewing sarcoma family tumors (ESFT) 70% event-free survival localized
- >20% bone marrow involvement survival <10%
- INTERVAL-COMPLETED trials show VDC/IE superior
- Adult patients have worse prognosis (50% vs 70%)
- Pelvic site 5-year survival 60% vs 75% extremity
- Second malignancies post-treatment 5-10% at 10 years
- Compression or busulfan-melphalan for high-risk
- 10-year overall survival 50-60% all stages
- Tumor size >8 cm survival 50%
- Age >15 years slightly worse prognosis
- Metastases to bone/bone marrow worse than lung-only
- Long-term cardiac toxicity from anthracyclines 5-10%
Treatment and Prognosis Interpretation
These statistics paint a sobering, hopeful, and complex portrait: while we've developed a powerful, albeit brutal, multi-modal assault that can cure most localized Ewing sarcoma, the disease remains a ferocious adversary when it metastasizes or presents in certain high-risk ways, trading some late toxicities for long-term survival.
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