EwingSarcoma

Ewing sarcoma is a malignant small round blue cell tumor that belongs to the Ewing family of tumors, which also includes extraskeletal Ewing sarcoma and peripheral primitive neuroectodermal tumor. It primarily affects children and adolescents and can arise in bone or in soft tissue (extraskeletal Ewing sarcoma).

Most cases are driven by chromosomal rearrangements involving the EWSR1 gene on chromosome 22. The most common fusion is EWSR1-FLI1, arising from t(11;22)(q24;q12). Other less frequent fusions, such as EWSR1-ERG, are also observed. These genetic changes underlie tumor development and aid in diagnosis.

Clinically, patients typically present with localized bone pain and swelling, sometimes with fever or malaise. Common sites include the pelvis, femur, tibia, and humerus, though tumors can occur anywhere. Imaging may reveal a destructive, permeative lesion with an aggressive periosteal reaction (often described as onion-skin), with MRI used to define extent. Chest imaging is important to assess for lung metastases.

Definitive diagnosis relies on tissue biopsy. Histology shows uniform small round blue cells. Immunohistochemistry often shows strong membranous CD99 expression. Molecular testing (FISH or RT-PCR) confirms the presence of an EWSR1 gene fusion.

Staging involves assessment for metastasis, typically with PET-CT or chest CT. Localized disease has a better prognosis than metastatic disease. Response to neoadjuvant chemotherapy correlates with outcome and guides subsequent therapy.

Treatment is multimodal: neoadjuvant chemotherapy (commonly vincristine, doxorubicin, cyclophosphamide, alternating with ifosfamide and etoposide – VDC/IE), followed by local control with surgery or radiotherapy, then consolidation chemotherapy. With modern therapy, localized disease has about a 60–70% long-term survival rate, while metastatic disease remains guarded. Late effects can include growth disturbances, infertility, and secondary malignancies.