Ewing Sarcoma

Ewing sarcoma is a type of paediatric cancer that typically forms in bone or soft tissue. It is a small round cell sarcoma with an unknown cause, often presenting in teenagers and young adults. This cancer is more prevalent among Caucasians and males, affecting approximately one in a million people per year in the United States.

Signs and Symptoms

Ewing sarcoma commonly presents with localised pain and swelling at the tumour site. The most frequently affected areas are the large long bones, pelvis, and chest wall. Patients may also experience intermittent fevers, anaemia, leukocytosis, and increased sedimentation rate, reflecting systemic inflammation. In about 25% of cases, the cancer has metastasized at diagnosis, complicating treatment and prognosis.

Distribution of Ewing Sarcoma: The most frequent locations are the large long bones and the pelvis.

Genetics

Ewing sarcoma is often linked to a genetic translocation between chromosomes 11 and 22, resulting in the fusion of the EWSR1 and FLI1 genes. This produces the EWS-FLI1 fusion protein, which plays a very important role in tumour development by altering gene expression through epigenetic mechanisms. This protein can increase cell pluripotency and oncogenesis by inhibiting microRNA and modifying chromatin structure.

Diagnosis

Diagnosis of Ewing sarcoma is confirmed through biopsy and analysis of histomorphologic, immunohistochemical, and molecular pathology findings.

Micrograph of metastatic Ewing sarcoma with characteristic cytoplasmic clearing on H&E staining, which was shown to be PAS positive

Ewing sarcoma is characterised as a small-blue-round-cell tumour with clear cytoplasm on H&E staining due to glycogen, demonstrated by positive PAS staining. CD99 is a typical immunostain marker, but other markers may be used to support the diagnosis. The most common chromosomal translocation associated with Ewing sarcoma is t(11;22)(q24;q12).

Medical Imaging

Imaging plays a very important role in diagnosing and managing Ewing sarcoma. Conventional radiographs reveal a "moth-eaten" pattern of lytic bone lesions and periosteal reactions such as the Codman triangle and onion peel appearance.

X-ray of a child with Ewing sarcoma of the tibia

MRI is essential for showing the full extent of bony and soft tissue involvement, while CT scans help define extraosseous tumour extent. Bone scintigraphy and dynamic contrast-enhanced MRI can also be useful in evaluating tumour response to therapy.

MRI slice showing Ewing sarcoma of the left hip (white area shown right)

Treatment

Treatment typically involves a combination of chemotherapy, radiation therapy, and surgery. Multidrug chemotherapy usually includes vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide. Surgery may involve limb salvage or amputation, and radiotherapy is used for localised disease control. Proton beam radiation is also an option for minimising damage to surrounding tissues.

Prognosis

The prognosis for Ewing sarcoma depends on several factors, including metastatic presence at diagnosis, tumour location, size, patient age, and lactate dehydrogenase levels. The five-year survival rate is about 70% for localised disease but drops to 30% for metastatic cases. Advances in multidisciplinary therapy have significantly improved survival rates.

Epidemiology

Ewing sarcomas represent 16% of primary bone sarcomas, with the highest incidence in adolescents aged 15-19 years. It is rare in children under five and adults over 30. The cancer is more common in people of European descent and less so in those of African descent. Incidence rates vary globally, with the United Kingdom reporting an average of six cases per year, primarily in males undergoing puberty.

Micrograph of metastatic Ewing sarcoma (right of image) in normal lung (left of image). PAS stain.

Self-assessment MCQs (single best answer)

Which demographic is most commonly affected by Ewing sarcoma?

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What is the typical age group for the onset of Ewing sarcoma?

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What is the most common chromosomal translocation associated with Ewing sarcoma?

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Which imaging modality is essential for showing the full extent of bony and soft tissue involvement in Ewing sarcoma?

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Which protein is typically produced as a result of the genetic translocation in Ewing sarcoma?

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What is the typical five-year survival rate for patients with localised Ewing sarcoma?

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Which histological feature is characteristic of Ewing sarcoma on H&E staining?

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Which chemotherapy drugs are commonly used in the treatment of Ewing sarcoma?

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What is a typical radiographic feature of Ewing sarcoma on X-ray?

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Which marker is typically used in immunostaining to help support a diagnosis of Ewing sarcoma?

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