Ewing's Sarcoma
Summary
Ewing's sarcoma is an aggressive malignant bone tumour that primarily affects children and adolescents aged 5-20 years. It is the second most common primary bone malignancy in this age group (after osteosarcoma). Histologically, it is a "small round blue cell tumour" characterised by the t(11;22) EWS-FLI1 translocation. It commonly arises in the diaphysis of long bones (femur, tibia, humerus) or flat bones (pelvis, ribs). The classic X-ray finding is "onion-skin" or "sunburst" periosteal reaction. Unlike osteosarcoma, Ewing's often presents with systemic symptoms (fever, raised inflammatory markers) and can mimic osteomyelitis. Treatment is multimodal: neoadjuvant chemotherapy, surgery (or radiotherapy), and adjuvant chemotherapy.
Key Facts
- Age: 5-20 years (peak 10-15)
- Histology: Small round blue cell tumour; t(11;22) EWS-FLI1
- Site: Diaphysis of long bones; Pelvis, Ribs
- X-ray: "Onion-skin" periosteal reaction
- Distinguishing Feature: Systemic symptoms (fever, weight loss, raised WCC)
- Treatment: Chemotherapy (highly sensitive) + Surgery/Radiotherapy
Clinical Pearls
"Ewing's Presents Like Infection": Unlike osteosarcoma, Ewing's often causes fever and raised inflammatory markers - easily mistaken for osteomyelitis.
"Diaphysis, Not Metaphysis": Ewing's typically arises in the diaphysis (shaft) of long bones, whereas osteosarcoma favours the metaphysis.
"Onion-Skin Sign": The lamellated periosteal reaction on X-ray looks like layers of an onion - classic for Ewing's.
"Chemotherapy First": Ewing's is highly chemosensitive. Neoadjuvant chemotherapy reduces tumour size and treats micrometastases before surgery.
Incidence
- 1-3 per million per year
- Second most common primary bone malignancy in children/adolescents
Demographics
- Peak age: 10-15 years
- M:F = 1.5:1
- Rare in Africans and Asians (predominantly Caucasian)
Sites
| Location | Frequency |
|---|---|
| Pelvis | 25% |
| Femur | 20% |
| Tibia/Fibula | 15% |
| Ribs | 10% |
| Humerus | 10% |
| Spine | 5% |
| Other | 15% |
Molecular Biology
- Characteristic translocation: t(11;22)(q24;q12)
- Fusion gene: EWS-FLI1 (85-90%)
- Other variants: EWS-ERG (5-10%)
- These fusion proteins are transcription factors driving oncogenesis
Histology
- Small round blue cells (similar size, high N:C ratio)
- PAS-positive (glycogen)
- CD99 (MIC2) positive on immunohistochemistry
Spread
- Local: Aggressive invasion
- Haematogenous metastases: Lung, bone, bone marrow (20-25% at diagnosis)
Symptoms
| Feature | Notes |
|---|---|
| Pain | Progressive, worse at night |
| Swelling | Localised mass |
| Systemic symptoms | Fever, weight loss, malaise (unlike osteosarcoma) |
| Limited function | If near joint |
| Pathological fracture | Occasionally presenting feature |
Laboratory Findings
Key Differential: Osteomyelitis
Inspection
- Swelling over affected bone
- Overlying skin may be warm, erythematous
Palpation
- Tender mass
- Firm, may be fixed
Function
- Reduced range of motion if near joint
- May have associated effusion
Imaging
| Modality | Findings |
|---|---|
| X-ray | Lytic lesion in diaphysis; "Onion-skin" or "sunburst" periosteal reaction; Soft tissue mass |
| MRI | Defines extent of tumour, soft tissue involvement, skip lesions |
| CT chest | Staging; Lung metastases |
| Bone scan / PET-CT | Staging; Bone metastases |
Biopsy
- Core needle or open biopsy
- Histology: Small round blue cells, CD99+, PAS+
- Molecular: EWS-FLI1 fusion (FISH or PCR)
Staging Workup
- MRI of primary
- CT chest
- Bone marrow biopsy
- Bone scan or PET-CT
Multimodal Approach
┌──────────────────────────────────────────────────────────┐
│ EWING'S SARCOMA MANAGEMENT │
├──────────────────────────────────────────────────────────┤
│ │
│ 1. NEOADJUVANT CHEMOTHERAPY: │
│ • 12-18 weeks prior to local treatment │
│ • Regimens: VDC/IE (Vincristine, Doxorubicin, │
│ Cyclophosphamide / Ifosfamide, Etoposide) │
│ • Assesses tumour response │
│ │
│ 2. LOCAL CONTROL: │
│ • Surgery (wide resection) - preferred if possible │
│ • Radiotherapy - if unresectable or poor margins │
│ • Ewing's is RADIOSENSITIVE │
│ │
│ 3. ADJUVANT CHEMOTHERAPY: │
│ • Continue for ~10-12 cycles total │
│ • Tailored to histological response │
│ │
│ 4. METASTATIC DISEASE: │
│ • Intensified chemotherapy │
│ • High-dose chemo + stem cell rescue in some │
│ • Local RT to metastases │
│ │
└──────────────────────────────────────────────────────────┘
Prognostic Factors
| Good | Poor |
|---|---|
| Localised disease | Metastases at diagnosis |
| Distal extremity | Axial/pelvic tumour |
| Good chemotherapy response | Poor response / viable tumour |
| Smaller tumour size | Large tumour (>cm) |
Of Disease
- Metastases (lung, bone, bone marrow)
- Pathological fracture
- Local recurrence
Of Treatment
- Chemotherapy: Myelosuppression, cardiotoxicity (doxorubicin), infertility
- Surgery: Limb dysfunction, amputation
- Radiotherapy: Growth disturbance, secondary malignancy
Survival
| Stage | 5-Year Survival |
|---|---|
| Localised | 65-75% |
| Metastatic at diagnosis | 20-30% |
| Recurrent | <10% |
Prognostic Markers
- Response to neoadjuvant chemotherapy (histological necrosis >90% = good)
- LDH level
- Tumour size and site
Key Guidelines
- ESMO Clinical Practice Guidelines: Bone Sarcomas
- Euro-Ewing Consortium Protocols
Key Evidence
Chemotherapy
- VDC/IE is standard regimen
Surgery vs Radiotherapy
- Surgery preferred for local control when feasible
- RT for unresectable or positive margins
What is Ewing's Sarcoma?
Ewing's sarcoma is a type of bone cancer that mainly affects children and teenagers. It usually starts in the bones of the legs, pelvis, or ribs.
What Are the Symptoms?
- Pain in the affected bone (often worse at night)
- Swelling or a lump
- Fever, tiredness, and weight loss (can look like an infection)
- Sometimes a broken bone without major injury
How is it Diagnosed?
- X-rays and MRI scans show the tumour
- A biopsy (tissue sample) confirms the diagnosis
How is it Treated?
Ewing's sarcoma is treated with a combination of:
- Chemotherapy (before and after surgery)
- Surgery to remove the tumour
- Radiotherapy (if surgery isn't possible or to ensure all cancer is gone)
What Are the Chances of Recovery?
With modern treatment, about 65-75% of children with localised Ewing's sarcoma survive long-term. Early diagnosis and treatment improve outcomes.
Primary Guidelines
- Euro-Ewing Consortium. Treatment Protocols for Ewing Sarcoma.
Key Studies
- Gaspar N, et al. Ewing Sarcoma: Current management and future approaches through collaboration. J Clin Oncol. 2015;33(27):3036-3046. PMID: 26304893