Soft tissue tumors: Ewing's tumors

Identity

Note	Ewing tumours form a histologically heterogeneous family belonging to the group of small round-cell tumours and derived from neural crests cells.

Classification

Ewing's tumors cover several distinct histological types: peripheral neuroepithelioma esthesioneuroblastoma Askin's tumour Ewing's sarcoma of bones and soft tissues

Clinics and Pathology

Epidemiology	peripheral neuroepithelioma is a very rare tumour (1% of all sarcomas); Ewing's sarcoma represents 5 to 15% of malignant bone and soft tissue tumours; two thirds of cases of Ewing's tumours occur before age 35 years, with a median age of 20 years.
Clinics	peripheral neuroepithelioma typically occurs in the extremities (buttock and upper thigh, shoulder and upper arm); esthesioneuroblastoma probably develops from the olfactive placode, in the nasal vault Ewing's sarcoma of bones affects preferentially long bones (especially the femur), the pelvis, and the ribs; extraskeletal Ewing's sarcoma occur in the paravertebral region and chest wall, often in association with vertebrae and ribs, and in lower extremities Askin's tumour is a paediatric tumour affecting mostly the chest wall and ribs
	Ewing's tumor : the tumor is composed of blastematous tissue with some differentiated glomerular structures associated with mesenchymal tissue and tubules. Courtesy Pierre Bedossa.
Pathology	peripheral neuroepithelioma show sheets or lobules of small round-cells with a scarce cytoplasm; cells are often arranged in rosettes with a neurofibrillar center (Homer-Wright rosettes) esthesioneuroblastoma is histologically very similar to neuroblastoma; rosettes may be present Askin's tumour seems to be more related to neuroepithelioma than to Ewing's sarcoma Ewing's sarcoma forms sheets of uniform small round-cells, sometimes arranged in a lobular pattern; the cytoplasm is scanty, pale stained and often vacuolated (glycogen); Ewing's sarcoma is considered as the less differentiated form of the Ewing's tumours family
Treatment	the treatment of Ewing's tumours is generally based on combined therapy with adjuvant chemotherapy, surgical resection and radiotherapy.
Prognosis	combined therapies have largely improved the prognosis of Ewing's tumours in the recent years; the prognosis is mainly determined by the presence of metastases at the time of diagnosis (15 to 35% of the cases); the 5-year survival rate is 10-35% in patients with mestastases, and 54-74% for patients with a localised disease at presentation.

Cytogenetics

Cytogenetics Morphological	about 90% of Ewing's tumours, whatever their type, show a t(11;22)(q24;q12); the translocation results in the fusion of the EWS gene with the transcription factor gene FLI1, leading to a hybrid transcript and an oncogenic chimeric protein; in about 5% of the cases, the EWS gene is involved in variant translocations: t(21;22)(q12;q12) and t(7;22)(p22;q12), leading to fusions EWS-ERG and EWS-ETV1, respectively.
	t(11;22)(q24;q12) in Ewing sarcoma, G- banding - top: courtesy Jean Luc Lai (with trisomy 8 on the right); - bottom: courtesy G. Reza Hafez, Eric B.Johnson, and Sara Morrison-Delap, UW Cytogenetic Services
Cytogenetics Molecular	additional anomalies in Ewing's tumours mainly consist in chromosome gains: +8 (45% of the cases) and, with a much lower frequency, trisomies 2, 5, 7, 9, 12 (between 10 and 15% of the cases); trisomy 1q, through unbalanced t(1q;16q), is observed in about 25% of the cases

Genes involved and Proteins

Gene Name	EWSR1
Location	22q12
Protein	RNA binding

Gene Name	FLI1
Location	11q24

Gene Name	ERG
Location	21q21

Gene Name	ETV1
Location	7p22

Result of the chromosomal anomaly

Hybrid Gene
Description	the 5' EWSR1 is fused to parts of either FLI1, ERG, or ETV1
Fusion Protein
Description	N terminal domain of EWS protein with DNA binding domain of FLI1, ERG (ETS family genes)
Oncogenesis	through transcription dysregulation

External links

Orphanet

Ewing sarcoma

Bibliography

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Turc-Carel C, Aurias A, Mugneret F, et al.

Cancer Genet Cytogenet 1988; 32: 229-238.

PMID 88210255

Chromosomes in Ewing's sarcoma. II. Non random additional changes, trisomy 8 and der(16)t(1;16).

Mugneret F, Lizard S, Aurias A, Turc-Carel C.

Cancer Genet Cytogenet 1988;32: 239-245.

PMID 88210256

Cytogenetic and pathologic aspects of Ewing's sarcoma and neuroectodermal tumors.

Stephenson CF, Bridge JA, Sandberg AA.

Hum Pathol 1992; 23: 1270-1277.

PMID 93052199

Gene fusion with an ETS DNA-binding domain in human tumours.

Delattre O, Zucman J, Plougastel B,et al.

Nature 1992; 359: 162-165.

PMID 92396239

The Ewing family of tumors - A subgroup of small-round-cell tumors defined by specific chimeric transcripts.

Delattre O, Zucman J, Melot T et al.

N Engl J Med 1994; 331: 294-299.

PMID 94293971

Soft tissue tumors.

Enzinger FM, Weiss SW.

Soft tissue tumors. 3rd. ed. pp 945-964, Mosby, St Louis, 1995.

A variant Ewing's sarcoma translocation fuses the EWS gene to the ETS gene ETV1.

Jeon IS, Davis JN, Braun BS et al.

Oncogene 1995; 10: 1229-1234.

PMID 95215084

Forest M, Tomeno B, Vanel D.

Orthopedic surgical pathology, pp 441-466, Churchill Livingstone, Edinburgh,1998.

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Contributor(s)

Written	06-1998	Jérôme Couturier

Citation

This paper should be referenced as such :

Couturier J . Soft tissue tumors: Ewing's tumors. Atlas Genet Cytogenet Oncol Haematol. June 1998 . URL : http://AtlasGeneticsOncology.org/Tumors/Ewing5010.html

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indexed on : Thu Apr 17 14:14:31 2008

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