Ewing's Sarcoma/Peripheral Neuroectodermal Tumor

Key Points:

  • Ewing’s Sarcoma is a malignant small round blue cell tumor found mostly in bone and soft tissue of the extremities and the axial skeleton. 
  • Ewing’s Family of Tumors (EFT) represent the second most common primary bone malignancy affecting children and adolescents.
  • In 85-to-90% of cases of EFT, a recurrent chromosomal translocation, t(11;22)(q24;q12), fuses EWSR1 gene on chromosome 22 to FLI1.
  • These lesions when located in the long bones are typically found in the diaphysis. They have a radiolucent (osteolytic) pattern with extension into the adjacent soft tissue. This lesion can also present as a primary soft tissue tumor.
  • Staging studies for the work-up include MRI of the extremity, whole body bone scan to evaluate for bone metastasis, CT scan of the chest to assess for metastatic disease and bone marrow biopsy to assess for bone marrow involvement.
  • Systemic chemotherapy, as well as surgery or radiation for local control, are the mainstays of treatment for patients with Ewing’s Sarcoma. Radiation is typically reserved for unresectable disease or when disease resection would be excessively morbid (pelvic and spine). 
  • The key prognostic factor in ES is the presence or absence of metastases. The approximate five-year survival rate for patients with localized disease is 70 percent, and 33 percent for those with metastases at diagnosis.

Description:

Ewing’s Sarcoma (ES) and Peripheral Neuroectodermal Tumor (PNET) are part of a spectrum of neoplastic diseases known as the Ewing sarcoma family of tumors. These diseases are associated with malignant small-cell tumors that can be found both in the bone and soft tissues of the extremities, but can also present in the axial skeleton. This family of tumors has the same chromosomal translocation t(11;22). Male patients outnumber female patients, and the femur is the most common site of origin. ES and PNET have similar presentations and treatment. There is usually a soft tissue mass associated with the bone lesion. There are no specific abnormal laboratory values that are diagnostic of these tumors. Elevated LDH level indicates a poor prognosis.

Epidemiology:

The Ewing’s sarcoma family of tumors represent the second most common primary bone malignancy affecting children and adolescents, after osteosarcoma. The peak incidence for these tumors is between 10 to 15 years of age. There is a slight male predominance. These tumors affect mainly Caucasians and are extremely uncommon among blacks and Asians. 

Clinical Findings:

Imaging Studies:

The plain radiographs of a patient with Ewing’s Sarcoma will usually demonstrate diffuse destruction of the bone that extends through the cortex, and would reveal a soft-tissue component. These lesions are classically associated with an onion-skin periosteal reaction.  The extraosseous soft tissue mass and the medullary canal involvement are best seen on MRI. Technetium bone scan is most useful in finding occult bone metastasis. Approximately 20% of these patients present with metastatic disease (lung is the most common site). The utility of PET or integrated PET-CT for initial staging is unclear and remains investigational.

Etiology:

No specific environmental exposures have been identified as risk factors for development of these tumors. They are thought to arise sporadically. 

Treatment:

The treatment for ES/PNET is a combination of chemotherapy and local control, either by surgery, radiation therapy, or a combination of both. The drugs commonly used include vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide. A multi-agent chemotherapy protocol using these agents is applied for 2-4 cycles before the management of the primary tumor. Surgical resection is recommended if the consequences of the resection do not have a significant impact on function. If the primary tumor cannot be resected without undue morbidity, or is unresectable, radiation alone can be used with good local control. Postoperative radiation can be used in the setting of close or positive margins. After the management of the primary tumor, a post-operative course of the same agents is usually continued.

For lesions involving either the upper or lower extremity, a limb salvage surgical resection can improve functional outcome without sacrificing local disease control as long as complete tumor resection is anatomically possible.  However, in some instances amputation or rotationplasty will result in the most functional outcome. Allografts and metal endoprostheses are common means of reconstructing bone defects that result from sarcoma resections. Expandable prostheses have been developed for reconstruction in skeletally immature children and allow lengthening of the limb, thus making limb salvage surgery an option in the younger skeletally immature patient.

Complications:

  • Oncologic complications can be due to the extent of disease and acute complications associated with the chemotherapy agents (vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide).
  • Growth disturbance and leg length discrepancy due to resection of an extremity growth plate.
  • Long-term complications from chemotherapy such as congestive heart failure, myelodysplasia, and acute leukemia.
  • Radiation associated sarcomas. Particularly if the total dosages surpass 60Gy.

References:

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Top Contributors:

Henock T. Wolde-Semait MD
Scott Rosenfeld MD