Oncology · Bone Tumors
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Ewing sarcoma is characterized by the t(11;22)(q24;q12) translocation, which results in the EWS-FLI1 fusion protein.
Radiographic imaging typically reveals a metadiaphyseal lesion with a classic onion-skin periosteal reaction.
Histopathology demonstrates small round blue cells that are CD99 positive and PAS positive.
Patients frequently present with localized bone pain and systemic symptoms such as fever, weight loss, and anemia.
The tumor most commonly arises in the metadiaphysis of long bones - especially the femur, tibia, and humerus - although the pelvis is the single most common anatomic region (about 18% of cases) in population-based series.
Ewing sarcoma is the second most common primary malignant bone tumor in children and adolescents.
Management requires a multimodal approach consisting of neoadjuvant chemotherapy, surgical resection, and radiation therapy.
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A 14-year-old male presents with a 3-month history of progressive mid-shaft thigh pain and intermittent low-grade fevers. Physical examination reveals localized tenderness and soft tissue swelling over the mid-femur. Laboratory studies show an elevated erythrocyte sedimentation rate (ESR) and leukocytosis. Radiographic imaging of the femur demonstrates a moth-eaten appearance with a lamellated onion-skin periosteal reaction in the metadiaphysis.
What is the most likely diagnosis?
Ewing Sarcoma
The combination of a metadiaphyseal lesion, systemic symptoms (fever), and the classic "onion-skin" periosteal reaction on X-ray is highly suggestive of Ewing sarcoma, which is confirmed by biopsy demonstrating the t(11;22) translocation/EWS-FLI1 fusion.
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Etiology / Epidemiology
Second most common primary bone malignancy in children/adolescents; peak incidence 10–20 years.
Clinical Manifestations
Localized bone pain and swelling; onion-skin periosteal reaction on imaging.
Diagnosis
Biopsy is the gold standard; look for small round blue cell tumor.
Treatment
Multimodal therapy: Chemotherapy followed by surgical resection or radiation.
Prognosis
Metastasis at presentation is the most significant negative prognostic factor.
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Epidemiology & Etiology
Predominantly affects non-Hispanic White males in the second decade of life. It is rarely seen in patients over age 30. Unlike osteosarcoma, it is not associated with Paget disease or prior radiation exposure.
Pertinent Anatomy
Most commonly arises in the metadiaphysis (often extending into the diaphysis) of long bones, particularly the femur, tibia, and humerus. By single anatomic region the pelvis is the most common primary site (about 18% of cases), with the femur the most commonly affected individual bone (about 11%); pelvic, other axial, and chest wall primaries often present with more aggressive clinical features.
Pathophysiology
Characterized by the t(11;22)(q24;q12) translocation, resulting in the EWS-FLI1 fusion protein. This oncogenic transcription factor drives uncontrolled cellular proliferation. Histology reveals sheets of uniform small round blue cells with scant cytoplasm.
Clinical Manifestations
Patients present with localized pain and a palpable mass, often mimicking osteomyelitis. Systemic symptoms like fever, weight loss, and anemia are common. Pathologic fractures may occur at the site of the lesion.
Diagnosis
Plain radiographs show a classic onion-skin periosteal reaction. Biopsy is the definitive diagnostic test. MRI is the gold standard for evaluating the extent of soft tissue involvement and marrow infiltration.
Treatment
Standard of care is neoadjuvant chemotherapy (interval-compressed VDC/IE: vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide) to shrink the tumor. Surgical resection is generally preferred for local control when the tumor can be removed with negative margins and acceptable function, largely because of the dose-dependent risk of radiation-induced secondary malignancy. Definitive radiation remains a standard primary local-control option for unresectable tumors and for pelvic or other axial primaries, where reported local control and survival are comparable across local-therapy modalities.
Prognosis
Five-year survival is approximately 80% for localized disease but drops significantly with distant metastasis (SEER/ACS data). Pulmonary metastasis is the most common site of spread and requires aggressive surveillance.
Differential Diagnosis
Osteosarcoma: sunburst periosteal reaction and Codman triangle
Osteomyelitis: positive blood or bone cultures; note that elevated ESR/CRP and leukocytosis occur in Ewing sarcoma as well and do not distinguish the two
Eosinophilic granuloma: punched-out lytic lesions
Lymphoma of bone: typically older patients with permeative bone destruction
Metastatic disease: usually older patients with a known primary malignancy