Ewing Sarcoma
Ewing sarcoma is a high-grade malignant small round cell tumor of bone and soft tissue, primarily affecting children and young adults. It represents the second most common primary malignant bone tumor after osteosarcoma. The hallmark of Ewing sarcoma is a chromosomal translocation involving the EWSR1 gene, most commonly t(11;22)(q24;q12), resulting in the EWSR1–FLI1 fusion gene.
Epidemiology
Peak incidence: ages 10–20 years.
Slight male predominance (M = 1.5:1).
Common locations: diaphysis of long bones (femur, tibia, humerus) and pelvis.
Rare in individuals of African or Asian descent.
Pathophysiology
Arises from primitive neuroectodermal cells (PNET family).
The EWSR1–FLI1 fusion protein acts as an aberrant transcription factor promoting uncontrolled proliferation.
Highly aggressive, with early hematogenous metastasis—most often to lungs, bone, and bone marrow.
Clinical Features
Localized pain and swelling, often progressive and worse at night.
Systemic symptoms (fever, fatigue, weight loss) may mimic infection.
Palpable mass, warmth, and tenderness in affected region.
Pathological fractures in advanced cortical destruction.
Imaging Findings
Radiographs:
Permeative, moth-eaten lytic lesion with cortical destruction.
Characteristic “onion-skin” periosteal reaction from layered new bone formation.
May exhibit Codman’s triangle or sunburst periosteal reaction in aggressive forms.
MRI:
Defines intramedullary extent and soft tissue mass.
Low-to-intermediate T1 and high T2 signal intensity.
Post-contrast enhancement of tumor and surrounding edema.
CT and PET-CT:
Evaluate cortical erosion, lung metastases, and treatment response.
Histopathology
Sheets of small round blue cells with scant cytoplasm and round nuclei.
Glycogen-rich cytoplasm (PAS positive).
CD99 (MIC2) shows strong membranous positivity.
EWSR1–FLI1 fusion gene detected via FISH or RT-PCR confirms diagnosis.
Differential Diagnosis
Condition Distinguishing Feature
Osteomyelitis Presence of fever, elevated inflammatory markers, response to antibiotics
Lymphoma of bone LCA positive, CD99 negative
Small cell osteosarcoma Osteoid production by tumor cells
Rhabdomyosarcoma Desmin and MyoD1 positivity
Neuroblastoma metastasis Pediatric patients, abdominal primary
Treatment
Ewing sarcoma requires a multimodal approach combining systemic and local therapy:
Neoadjuvant chemotherapy – for tumor control and early metastasis treatment.Standard protocol: VDC/IE (Vincristine, Doxorubicin, Cyclophosphamide / Ifosfamide, Etoposide).
Administered for 12–14 cycles over ~10 months.
Local controlLimb-salvage surgery preferred if negative margins achievable.
Radiotherapy indicated for unresectable lesions or positive margins.
Combined surgery and RT may enhance local control but increase complications.
Adjuvant chemotherapyContinued systemic therapy post-surgery for micrometastatic disease.
Prognosis
Localized disease: 5-year survival ~70–75%.
Metastatic disease: 5-year survival ~25–30%.
Poor prognostic indicators:
Metastases at presentation (especially to bone or bone marrow)
Large tumor size (>8 cm)
Pelvic location
Poor histologic response to neoadjuvant chemotherapy (<90% necrosis).
Key Points
Second most common primary malignant bone tumor in youth.
Defined by EWSR1–FLI1 fusion and CD99 positivity.
Managed with VDC/IE chemotherapy and limb-salvage surgery.
Prognosis strongly linked to metastatic status and histologic response.
References
Ladenstein R et al. Ewing Sarcoma: Current Management and Future Directions. J Clin Oncol. 2021;39(26):3039–3053.
Gaspar N et al. Ewing Sarcoma: ESMO–EURACAN Clinical Practice Guidelines. Ann Oncol. 2022;33(12):1344–1358.
Balamuth NJ, Womer RB. Ewing’s Sarcoma. Lancet Oncol. 2010;11(2):184–192.
Patel SR, Benjamin RS. Chemotherapy for Bone Sarcomas: Ewing and Beyond. Cancer Treat Rev. 2023;115:102521.
