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Ewing’s Sarcoma

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- Discussion:
    - prevalence:
         - it represents approx 7% of all primary bone malignancies; 
         - second most common primary malignant bone tumor (behind osteosarcoma) (2.1 per 1 million children)
         - Ewing's sarcoma is more common in males and is rare in blacks;
    - source:
         - uncertain origin;
         - may arise from primitive reticulum cells of marrow;
         - common karyotypic translocation between chromosomes 11 and 22;
    - age:
         - it is a tumor of children & young adults, w/ most cases occurring between ages of 10 and 20 years;
         - 3% of Ewing's sarcoma occurs in children less than 3 years of age;
         - 64% of Ewing's sarcoma occur in the second decade;
    - genetics:
         - expresses p30/32 MIC2 antigen (cell surface glycoprotein);
         - 85% contain chromosomal translocation at the t(11;22)(q24;q12);
    - prognosis:
         - potentially the most lethal of all the bone tumors;
         - most important adverse prognostic factor was metastatic disease detectable at the time of diagnosis;
         - it almost always presents as a stage IIb lesion;
         - before routine use of adjuvant chemo, pts w/ Ewing's were treated w/ XRT alone, & 5 year survival rate was no more than 15%;
         - w/ use of adjuvant chemo, 5 year survival rate to more than 60%;
         - w/ non metastatic Ewing's, disease free survival is 55-70% versus 22-33% for metastatic;
         - pts require careful follow-up, due to post-XRT osteosarcoma;
         - pelvic ewing's:
               - tumors in pelvis are typically detected later & are therefore larger, with a poorer prognosis;
               - 5 year survival rate is about 25%;
    - differential diagnosis:
         - osteomyelitis, osteolytic osteosarcoma, & EOG, & neuroblastoma;
         - in infants and young children, rule out neuroblastoma (only 2% of patients with ewings sarcoma are less than 5 years of age);
               - ewing's sarcoma will stain positve for PAS (cytoplasmic glycogen) and will have a positive vimentin stain;
               - neuroblastoma stains negative for PAS and has a negative vimentin stain, but neuroblastoma is positive for neuron
                        -specific enolase and neurofilament;
         - midshaft lesion w/ large, assoc soft-tissue swelling suggests either infection or Ewing's sarcoma;
         - osteogenic sarcoma tends to be more metaphyseal;
         - ref: Ewings sarcoma masquerading as osteomyelitis


- Clinical Presentation:
    - may mimic osteomyelitis w/ fever, elevated WBC, & sed rate, wt loss, anemia;
    - enlarging, tender, bony prominence w/ an associated soft tissue mass;
    - sites:
           - femoral diaphysis > pelvis, tibia,  humerus, fibula & ribs;
                  - develops in axial skeleton in large proportion of pts (about 40 %);
           - tumors in pelvis are typically detected later & are therefore larger, with a poorer prognosis;
           - lesion also has peculiar predilection for shaft of fibula
           - an area containing little or no hematopoietic marrow;
           - it occasionally arises in extraosseous sites ("soft-tissue, Ewing's").
           - distant metastases are noted at diagnosis in about 20% of cases;


- Radiographs:
    - permeative diaphyseal tumor w/ mottled, or patchy density;
    - cortical involvement may produce periosteal reaction, "onion skin" pattern;
    - references:
         - Is PET Useful in Detecting Occult Nonpulmonary Metastases in Pediatric Bone Sarcomas?


- Microscopic Features:


- Treatment:
    - treatment consists of chemotherapy, surgical resection & possible XRT;
           - w/ combined therapy pt survival has improved.
           - reference: Outcomes and Prognostic Factors for Ewing-Family Tumors of the Extremities
    - some authors recommend bone marrow aspiration and biopsy at two or more sites for staging purposes;
    - radiotherapy:
           - approx 75-85 % of primary ewing's tumors are sensitive, depending primarily on tumor size and site;
           - poor to fair results are expect w/ large tumors located in axial skeleton;
           - obviously XRT is not desirable in children because of its effect on the growing limb and because of the possibility for causing 
                     secondary tumors (can be up to 20%);
           - ref: Improved Prognosis for Patients with Ewing Sarcoma in the Sacrum Compared with the Innominate Bones: The Scandinavian Sarcoma Group Experience.
    - chemotherapy:
           - vincristine, doxorubicin, cyclophosphamide, adriamycin, ifosfamide, and etoposide;
           - addition of chemotherapy with surgery increases survival to greater than 70% at 5 years;
           - references:
                   - Ewing’s sarcoma. only patients with 100% of necrosis after chemotherapy should be classified as having a good response
                   - Tumor volume as a predictor of necrosis after chemotherapy in Ewing's sarcoma.

    - wide surgical excision:
           - preferred over XRT if:
                   - involved bone is expendable (eg fibula, rib, clavicle);
                   - if XRT would damage growth plate (XRT may cause premature closure of growth plate);
                   - if there is pathologic frx;
           - limb salvage w/ insertion of long stem tibial component:

             



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References

Local and systemic control in Ewing's sarcoma of the femur treated with chemotherapy, and locally by radiotherapy and/or surgery.

Is PET Useful in Detecting Occult Nonpulmonary Metastases in Pediatric Bone Sarcomas?