Ewing sarcoma
- Lesion
An aggressive bone and soft tissue cancer of children and teens made of small round cells, driven by a gene fusion; it can mimic infection.
What it is
Ewing sarcoma is a malignant small round cell tumour of bone and soft tissue in children and adolescents. In most cases a translocation fuses EWSR1 on chromosome 22 with FLI1 on chromosome 11, t(11;22), creating an abnormal transcription factor that reprograms the cell. It favours the diaphysis of long bones and the pelvis, often with fever, raised ESR and leukocytosis that mimic osteomyelitis. Despite its aggressiveness, modern chemotherapy, surgery and radiation cure most patients with localized disease.
Structure
- Gross: soft, tan-white tumour with haemorrhage and necrosis, filling the marrow and extending into soft tissue.
- Micro: monotonous sheets of small cells slightly larger than lymphocytes, with round nuclei and fine chromatin.
- Cytoplasm is scant and clear because of glycogen; few stroma and little or no matrix.
- Homer Wright rosettes (cells around a fibrillary centre) show neuroectodermal differentiation.
Step by step
- A translocation fuses EWSR1 with an ETS family gene (usually FLI1).
- The fusion protein binds repetitive GGAA microsatellites and switches on genes for growth.
- It also represses differentiation and tumour-suppressor programs.
- Mesenchymal or neural crest-like progenitor cells become small round malignant cells.
- The tumour grows through bone into soft tissue and spreads to lungs, bone and marrow.
Small round blue cell tumours of childhood
| Tumour | Typical site | Key marker or genetics | Clue |
|---|---|---|---|
| Ewing sarcoma | Bone diaphysis, pelvis | CD99, NKX2-2; EWSR1-FLI1 | Onion-skin periosteum, fever |
| Rhabdomyosarcoma | Head and neck, genitourinary, limbs | Desmin, myogenin; PAX3/7-FOXO1 in alveolar type | Strap cells, botryoid grapes |
| Neuroblastoma | Adrenal, paraspinal | Synaptophysin, PHOX2B; MYCN amplification | Urine catecholamines, young children |
| Lymphoblastic lymphoma or leukaemia | Mediastinum, marrow | TdT, CD45 | Blood and marrow involvement |
| Wilms tumour (blastemal) | Kidney | WT1 | Triphasic histology |
Markers
- CD99 (membranous)
- NKX2-2
- FLI1
- EWSR1 break-apart FISH
Clinical notes
- Painful, sometimes warm swelling with fever and a high ESR: it can be mistaken for osteomyelitis.
- Metastases at diagnosis (lungs, bone, marrow) are the main adverse factor.
- Treated with multi-agent chemotherapy plus surgery or radiation.
Test yourself
Think of the answer, then tap the question to see it.
Which translocation is typical of Ewing sarcoma?
t(11;22), fusing EWSR1 with FLI1.
Which immunohistochemical marker is typically strongly positive in Ewing sarcoma?
CD99, with membranous staining (also NKX2-2).
Why can Ewing sarcoma be confused with osteomyelitis?
It causes fever, pain, warmth, leukocytosis and a raised ESR.
Where in the long bone does Ewing sarcoma usually arise?
In the diaphysis.
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Ewing sarcoma: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025); Ewing Sarcoma and Undifferentiated Small Round Cell Sarcomas of Bone and Soft Tissue Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2025).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.