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A. Definition navigator

  1. Small round blue cell tumor of bone or soft tissue
  2. High grade, small, differentiated, round cell bone sarcoma
    1. Unclear etiology; defined as Ewing's when histologically undifferentiated
    2. Cells have neuroectodermal markers of differentiation
    3. PNET when more neurally differentiated by immunohistochemistry
    4. CNS PNETs include medulloblastoma and other supra/ infratentorial tumors
  3. Usually occurs on diaphysis of long bones
  4. Variant high-grade synovial cell sarcomas can occur [4]
  5. Intensive chemotherapy with surgery and/or radiation affords up to 70% cure rates

B. Epidemiologynavigator

  1. 2 new cases per million people per year
  2. 5-10% of all bony sarcomas (second most common bone tumor of children)
  3. Peak onset between 10 and 15 years
  4. Rare in blacks and Asians for unclear reasons
  5. No association with familial cancer syndromes or radiation exposure

C. Pathogenesisnavigator

  1. The EWS gene, located on chromosome 22, has unknown cellular function
  2. Associated with the following translocations of EWS on chr 22: [5]
    1. t(11;22) - FL11 gene on chr 11
    2. t(21;22) - ERG gene on chr 21
    3. t(7;22) - ETV1 on chr 7
    4. Translocations to E1AF on chr 17 or FEV on chr 2 are rare
  3. Genetic changes involve a loss of the usual regulatory sequences for the EWS gene and replacement with transcription factor gene
  4. EWS gene may be future target for gene therapy

D. Clinical Presentationnavigator

  1. Pain, swelling, mass or warmth in bone or soft tissue
  2. Systemic signs: weight loss or fevers
  3. Tends to arises in flat bones and diaphysis of long bones, most commonly:
    1. Pelvis
    2. Femur
    3. Humerus
  4. Occasionally arises in extraosseous sites such as soft tissue of the chest wall
  5. About 25% of cases have demonstrable metastases at presentation
    1. Lung is by far the most common
    2. Metastases to bone are seen
    3. Bone marrow involvement also common
  6. Thus, hematogenous spread of tumors is common

E. Diagnosis and Stagingnavigator

  1. Plain radiograph: lytic or sclerotic lesion of affected bone
  2. Further delineation with CT with bone windows of affected area
  3. Staging: MRI of site, chest CT, bone scan
  4. Surgical pathology showing small round blue cells with Homer-Wright pesudorosettes
  5. Staging evaluation to assess for metastatic disease
    1. MRI of involved site
    2. Chest CT
    3. Bone scan
    4. Bone marrow biopsy

F. Treatmentnavigator

  1. Local Control
    1. Need to ablate primary for chance at cure
    2. Surgical resection best option
    3. High dose radiation therapy associated with up to 20% incidence of secondary tumors
  2. Systemic Chemotherapy
    1. Over 90% of cases have at least micrometastatic at presentation
    2. Typical regimens: vincristine, doxorubicin, cyclophosphamde, dactinomycin alternating with ifosfamide/VP-16 (etoposide)
    3. Chemotherapy typically given both prior to and after surgical resection
  3. Treatment of Localized Ewing's Sarcoma
    1. Chemotherapy as above (for micrometastatic disease)
    2. 8-12 months of therapy
    3. Surgery and/or radiation therapy for local tumor control
    4. Ifosfamide and etoposide added to standard therapy for Ewing's Sarcoma improves outcome for non-metastatic (but not metastatic) disease [6]
  4. Treatment of Metastatic Ewing's Sarcoma
    1. Chemotherapy as above and/or
    2. High dose chemotherapy with stem-cell support (limited success)
    3. Treatment for 8-12 months
    4. Surgery and/or radiation therapy for local tumor control

G. Prognosis [6]navigator

  1. No detectable metastases at presentation
    1. Results suggest micrometasites in most cases
    2. Surgery alone: <10% disease free survival (DFS)
    3. Surgery with Chemotherapy: 50-60% DFS at 3-5 years
  2. Detectable metastases at presentation: 22% overall survival at 5 years
  3. Relapses
    1. Can occur up to 10 years after initial diagnosis
    2. Some DFS if able to resect all recurrent tumor and undergo adjuvant chemotherapy
  4. Prognosis based on genotype is under investigation

References navigator

  1. Grier HE. 1997. Pediatric Clinics of North America. 44(4): 991 abstract
  2. Haeglem BP. 1996. Pediatric Clinics of North America. 43(4): 967 abstract
  3. Arndt CAS and Crist WM. 1999. NEJM. 341(5):343
  4. Cohen IJ, Issakov J, Avidgad S, et al. 1997. Lancet. 350(9091):1679
  5. Delattre O, Zucman J, Melot T, et al. 1994. NEJM. 331(5):294 abstract
  6. Grier HE, Krailo MD, Tarbell NJ, et al. 2003. NEJM. 348(8):694 abstract