THE EWING FAMILY OF TUMORS: Ewing's Sarcoma and Primitive Neuroectodermal Tumors
Section snippets
CAUSE
The cause of Ewing's sarcoma is unknown. Radiation exposure does not appear to be a common cause of Ewing's sarcoma. For example, no increased incidence occurred after exposure to nuclear fallout in Japan.80 The tumor may occur after prior treatment for cancer, including radiotherapy73; however, the incidence is quite low. In a large study of secondary bone tumors after radiotherapy, 69% of the tumors were osteosarcoma, whereas only 3% were Ewing's sarcoma.75
Ewing's sarcoma does not appear to
MOLECULAR GENETICS
Nearly all Ewing's sarcomas and PNET have a clonal translocation seen in the malignant cells. By far, the most common translocation is between the long arms of chromosomes 11 and 22. This translocation can be found by standard cytogenetics in over 80% of the Ewing family of tumors, and is seen using molecular techniques in over 90%.12, 76, 79 The break point of this common translocation has been cloned; the rearrangement occurs within the EWS gene on chromosome 22 and the FLI-1 gene on
PATHOLOGY
Ewing's sarcoma and PNET belong to the group of neoplasms commonly referred to as small round cell tumors. These include neuroblastoma, rhabdomyosarcoma, and non-Hodgkin's lymphoma. The differentiation of Ewing's tumor from the other entities may occasionally be difficult, especially in the soft tissue variants.74 The individual cells in Ewing's sarcoma are round, of moderate size, have clear and frequently quite scant cytoplasm, and round to oval nucleus. Small to moderate areas of necrosis
CLINICAL PRESENTATION
Pain or swelling, or both, at the site of the primary tumor are, by far, the most common presenting symptoms in Ewing's sarcoma–PNET of bone and soft tissue. Unlike osteosarcoma, patients with Ewing's sarcoma may also present with systemic signs and symptoms such as weight loss, fever, and increased sedimentation rate. Systemic signs are more common in patients presenting with metastases.55 The presence of systemic symptoms often brings osteomyelitis into the differential diagnosis of patients
STAGING AND PROGNOSIS
The staging workup for Ewing's sarcoma is based on proper imaging of the primary tumor and sites of likely metastases: plain films and MR imaging of the primary site, chest radiographs and CT scan of the lung, bone scan, and bone marrow biopsy. Laboratory studies should include a complete blood count, an erythrocyte sedimentation rate (increased in up to 50% of patients), and baseline chemistries. The tumor biopsy should be done at a center with facilities to provide immunohistochemistry, solid
THERAPY
Treatment of Ewing's sarcoma requires eradication of the tumor at both its presenting site (local control) and the sites of metastatic or micrometastatic disease. Nearly all patients with Ewing's sarcoma have micrometastatic disease (i.e., tumor cells outside the primary site that cannot be detected by standard methods) at the time of diagnosis. This is evidenced by a cure rate of less than 10% when Ewing's sarcoma is treated with radiotherapy or surgery to the local site alone.18 In addition,
SUMMARY
There has been an explosion of new knowledge regarding the Ewing family of tumors over the past 5 to 10 years. Classical Ewing's sarcoma and PNET are now known to be the same tumor with variable differentiation, defined by a translocation between the EWS gene on chromosome 22 with one of three ETS-like genes, especially the FLI-1 gene on chromosome 11. Molecular techniques used to identify this translocation along with the knowledge that the protein product of the MIC2 gene is highly expressed
References (84)
- et al.
Radiation therapy in Ewing's sarcoma: An update of the CESS 86 Trial
Int J Radiat Oncol Biol Phys
(1995) - et al.
Long-term follow-up of Ewing's sarcoma of bone treated with combined modality therapy
Int J Radiat Oncol Biol Phys
(1991) - et al.
Ewing's sarcoma of bone: Clinicopathologic aspects of 303 cases from the Intergroup Ewing's Sarcoma Study
Hum Pathol
(1983) - et al.
Rarity of Ewing's sarcoma in China
Lancet
(1980) - et al.
The response to initial chemotherapy as a prognostic factor in localized Ewing's sarcoma
Eur J Cancer Clin Oncol
(1985) - et al.
The role of radiation therapy in the management of non-metastatic Ewing's sarcoma of bone. Report of the Intergroup Ewing's Sarcoma Study
Int J Radiat Oncol Biol Phys
(1981) - et al.
Ewing's sarcoma: Routine diagnostic utilization of MIC2 analysis: A Pediatric Oncology Group/Children's Cancer Group Intergroup Study
Hum Pathol
(1994) - et al.
Ewing's sarcoma: Surgical resection as a prognostic factor
Int J Radiat Oncol Biol Phys
(1988) - et al.
Prognostic factors in the treatment of Ewing's sarcoma
Radiother Oncol
(1987) - et al.
Is neuro-ectodermal differentiation of Ewing's sarcoma of bone associated with an unfavourable prognosis?
Euro J Cancer
(1995)
Chromosomes in Ewing's sarcoma. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12)
Cancer Genet Cytogenet
Cytogenetic characterization of selected small round cell tumors of childhood
Canc Genet Cytogenet
Incidence of malignant tumors in U.S. children
J Pediatr
MIC2 is a specific marker for Ewing's sarcoma and peripheral primitive neuroectodermal tumors. Evidence for a common histogenesis of Ewing's sarcoma and peripheral primitive neuroectodermal tumors from MIC2 expression and specific chromosome aberration
Cancer
The treatment of localized Ewing's sarcoma: The experience at the Istituto Ortopedico Rizzoli in 163 cases treated with and without adjuvant chemotherapy
Cancer
Molecular assays for chromosomal translocations in the diagnosis of pediatric soft tissue sarcomas
JAMA
MR imaging of osteogenic and Ewing's sarcoma
Am J Radiol
Myeloablative radiochemotherapy and hematopoietic stem-cell rescue in poor-prognosis Ewing's sarcoma
J Clin Oncol
Multimodal therapy for the management of nonpelvic, localized Ewing's sarcoma of bone: Intergroup study IESS-II
J Clin Oncol
Ewing's sarcoma metastatic at diagnosis: Results and comparisons of two intergroup Ewing's sarcoma studies
Cancer
Ewing's sarcoma: Value of tumor necrosis as a predictive factor
Bull Cancer
Neuroepithelioma (primitive neuroectodermal tumor) and Ewing's sarcoma: At least a partial consensus
Arch Pathol Lab Med
The Ewing family of tumors: A subgroup of small-round-cell tumors defined by specific chimeric transcripts
N Engl J Med
Multiplex RT-PCR assay for the differential diagnosis of alveolar rhabdomyosarcoma and Ewing's sarcoma
Am J Pathol
Diffuse endothelioma of bone. Proc New York Path Soc 21:17, 1921
Reprinted in Clin Orthop Rel Res
Rarity of Ewing's sarcoma among U.S. negro children
Lancet
Long-term outcome of patients with monostotic Ewing's sarcoma treated with combined modality
Med Pediatr Oncol
Prognostic significance of tumor volume in localized Ewing's sarcoma of bone in children and adolescents
Cancer Res Clin Oncol
Diagnosis and Management of Malignant Solid Tumors in Infants and Children
Improved outcome in non-metastatic Ewing's sarcoma and PNET of bone with the addition of ifosfamide and etoposide to vincristine, adriamycin, cyclophosphamide, and actinomycin: A Children's Cancer Group and Pediatric Oncology Group report
Proc Am Soc Clin Oncol
Adding ifosfamide and etoposide to vincristine, cyclophosphamide, adriamycin, and actinomycin improves outcome in non-metastatic Ewing's and PNET: Update of CCG/POG study
Med Pediatr Oncol
Prognostic value of histopathology in Ewing's sarcoma: Long term follow-up of distal extremity primary tumors
Cancer
Long-term survival in patients with Ewing's sarcoma relapsing after completing therapy
Med Pediatr Oncol
Therapy for localized Ewing's sarcoma of bone
J Clin Oncol
Percutaneous biopsy of peripheral primitive neuroectodermal tumors and Ewing's sarcomas for cytogenetic analysis
AJR Am J Roentgenol
Magnetic resonance imaging of bone and soft tissue tumors: Early experience in 31 patients compared with computed tomography
Skeletal Radiol
Treatment of clinically localized Ewing's sarcoma with radiotherapy and combination therapy
Cancer
The neuroectodermal tumor of bone
Am J Surg Pathol
A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1
Oncogene
Ewing's sarcoma in female siblings. A clinical report and review of the literature
Cancer
High-dose ifosfamide with mesna uroprotection in Ewing's sarcoma
Cancer Chemother Pharmacol
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Address reprint requests to Holcombe E. Grier, MD, Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115
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From the Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital Boston; and the Department of Pediatrics, Harvard Medical School, Boston, Massachusetts