Access Keys:
Skip to content (Access Key - 0)

Ewing sarcoma

Tumor biology and incidence

  • Small, malignant, round-cell tumor
  • Second most common primary malignant bone tumor in children
  • Accounts for approximately 10% of all primary malignant bone tumors
  • Recent genetic, biochemical, and electron microscopic studies suggest Ewing sarcoma is a spectrum of tumors
  • Closely related to peripheral/primitive neuro-ectodermal tumor (PNET)
    • Aame chromosomal translocation between chromosomes 11 and 22
    • Both thought to arise from the neural crest
    • Similar presentations
    • Identical treatments
    • Almost identical histologic characteristics


5-25 years; rare in children younger than age 5 or adults older than age 30


M:F = 3:2


  • Pain and localized swelling, representing an associated soft tissue mass
  • Constitutional symptoms, such as fever, malaise, and weight loss common, especially with metastatic disease
  • 25% of patients present with overt metastases
    • Poor prognostic finding
    • Metastases typically found in lungs, bone marrow, bone

Physical findings

  • Mass often warm, firm, and tender, almost presenting like an infective/inflammatory lesion
  • If located in rib, may have pleural effusion
  • If located in spine or pelvis, may have neurologic signs


  • Increased ESR and LDH common.
  • Possibly anemia and leukocytosis

Plain films

  • Femur, tibia, fibula, pelvis most common sites
  • May be found in humerus, clavicle, scapula, ribs
  • In long tubular bones, lesion often found in diaphysis, but could be metaphyseal/epiphyseal

Usually greater than 5 cm

Tumor effect on bone
  • Diffuse, permeative bone destruction
  • Destruction of bone may be minimal compared with soft tissue mass
Bone response to tumor
  • Poorly defined margins
  • Permeative or moth-eaten bone destruction
  • Onion skinning periosteal response
  • Dense host bone sclerosis rare

None produced

  • Often moth-eaten but structurally intact underlying the typical soft tissue mass
    • Caused by rapid growth of tumor through the Haversian canals of intact cortex
    • Onion skinning periosteal reaction frequent, as are "sunburst" or "spiculated" patterns of periosteal reaction
Soft tissue mass
  • Often present (large, non-calcified)
  • May be more visible on radiographs than bone lesion

Bone scan and chest CT

  • Necessary for systemic staging
  • Remote site of bone marrow aspiration also needed to complete staging


  • The extraosseous soft tissue mass and medullary canal involvement can be best seen on MRI; usually more extensive than what was expected from plain radiographs
  • Usually repeated after several cycles of chemotherapy
    • Assess the response of the tumor to neoadjuvant chemoherapy
    • Help plan definitive treatment of primary lesion

Differential diagnosis

  • Osteomyelitis
    • Presents with pain, fever, elevated WBC count, elevated ESR
    • Can involve diaphysis or metaphysis as well
  • Lymphoma
  • Osteosarcoma
  • Eosinophilic granuloma
  • MFH
  • Fibrosarcoma
  • Metastatic neuroblastoma (in very young patients)

Natural History

  • Advances in chemotherapy have improved long-term survival rate from 10% to over 70%
  • Good prognosis: small, distal extremity lesion
  • Poor prognosis: metastases on presentation (other bones or lungs), proximal extremity or axial, large lesion


  • Gross: Gray-white tumor with a variable amount of necrosis, hemorrhage, or cyst formation
    • At times, the tumor tissue may be almost liquid, mimicking a purulent mass
  • Microscopic: Numerous small, round cells with a diffuse homogeneous growth pattern and sparse intercellular stroma
    • Cells have ill-defined borders and finely dispersed chromatin pattern
    • Cells uniform
    • Mitotic activity seldom high
    • Glycogen granules in cytoplasm, which produce positive periodic acid-Schiff (PAS) stain on routine histology
  • Recent advances in cytogenetics and immunohistochemistry allow for more precise diagnostic evaluations
    • Ewing sarcoma/PNET cells strongly express p30/32 MIC2 antigen, a cell-surface glycoprotein encoded by the MIC2 gene
    • MIC2 analysis has sensitivity of 95% in diagnosing Ewing sarcoma/PNET
    • Cytogenetic studies have revealed that 85% of Ewing sarcoma/PNET contain a translocation either of chromosomes 11 and 22 [t(11;22)] or of chromosomes 21 and 22 [t(21;22)]
    • Resultant fusion gene is composed of part of the EWS gene from chromosome 22 and the FLY1 gene from chromosome 11 or the ERG gene from chromosome 21


  • Non-metastatic cases treated with administration of multiagent chemotherapy to achieve local control
  • Chemotherapeutic agents most widely used include:
    • Vincristine
    • Cyclophosphamide
    • Doxorubicin
    • Ifosfamide
    • Etoposide
  • Chemotherapy dramatically reduces soft tissue component of lesion in most cases
  • 2-year disease-free survival rates vary from 50% to 80% in patients treated with chemotherapy
  • Resection of primary lesion with wide surgical margins recommended for local control of Ewing sarcoma/PNET, provided functional consequences of resection are acceptable
  • Limb-salvage surgery possible in most patients
  • Amputation may be necessary if limb-salvage is contraindicated
  • Postoperative irradiation usually recommended when surgical margins are close and significant viable tumor is present in resected specimen
  • Irradiation alone can be used when there is extreme morbidity of resecting primary tumor
  • Total dosage should be kept as low as possible, usually around 50 Gray, because dosages of more than 60 Gray can be associated with increased incidence of secondary irradiation-induced sarcomas

Peer Review

OrthopaedicsOne Peer Review Workflow is an innovative platform that allows the process of peer review to occur right within an OrthopaedicsOne article in an open, transparent and flexible manner. Learn more

Instructions for Authors

Read our Instructions for Authors to learn about contributing or editing articles on OrthopaedicsOne.

Content Partner

Learn about becoming an OrthopaedicsOne Content Partner.

Academic Resources

Resources on Ewing sarcoma from Pubget.

The license could not be verified: License Certificate has expired!
Orthopaedic Web Links

Internet resources validated by

The license could not be verified: License Certificate has expired!
Related Content

Resources on Ewing sarcoma and related topics in OrthopaedicsOne spaces.

Page: Ewing sarcoma (OrthopaedicsOne Articles)
Page: Osteosarcoma (OrthopaedicsOne Articles)
Page: Polyostotic conditions (OrthopaedicsOne Articles)
Page: Osteoid osteoma (OrthopaedicsOne Articles)
Page: Unicameral bone cyst (OrthopaedicsOne Articles)
Page: Chondroblastoma (OrthopaedicsOne Articles)
Page: Fibrous dysplasia (OrthopaedicsOne Articles)
Page: Giant cell tumor (OrthopaedicsOne Articles)
Page: Osteoblastoma (OrthopaedicsOne Articles)
Page: Aneurysmal bone cyst (OrthopaedicsOne Articles)
Showing first 10 of 449 results