Ewing sarcoma

Other Names: Ewing's tumor; Sarcoma, Ewing's; Ewing tumor; Ewing's sarcoma

Ewing sarcoma is a malignant (cancerous) bone tumor that affects children. It can occur any time during childhood and young adulthood, but usually develops during puberty, when bones are growing rapidly. The tumor may arise anywhere in the body, usually in the long bones of the arms and legs, the pelvis, or the chest. It may also develop in the skull or the flat bones of the trunk.

Distribution of Ewing's sarcoma: Most frequent locations are the large long bones and the pelvis.

Micrograph of a metastatic Ewing's sarcoma with the characteristic cytoplasmic clearing on H&E staining, which was showing to be PAS positive.

Cause

The cause of Ewing sarcoma is unknown. Most cases are thought to occur randomly and many involved a reciprocal translocation between chromosomes 11 and 22. Chromosomal studies have found that Ewing sarcoma cells are often characterized by an abnormal change in their genetic makeup known as a reciprocal translocation. The most common mutation, occurring in approximately 85% of Ewing sarcoma tumors, involves two genes, the EWSR1 gene on chromosome 22 and the FLI1 gene on chromosome 11. This rearrangement of genetic material between chromosomes 22 and 11 fuses part of the EWSR1 gene with part of the FLI1 gene, creating the EWSR1/FLI1 fusion gene. This mutation is acquired during a person's lifetime and is present only in tumor cells. This type of genetic change, called a somatic mutation, is not inherited. In extremely rare cases, Ewing sarcoma may develop as a second malignancy, which means that the condition develops as a late-onset complication of earlier treatment for another form of cancer.

Inheritance

This condition is generally not inherited but arises from a mutation in the body's cells that occurs after conception (somatic mutation). Most cases are considered to be sporadic. However, the incidence of neuroectodermal and stomach malignancies is increased among family members of patients with tumors of the Ewing sarcoma family.

Symptoms

There are few symptoms. The most common is pain and occasionally swelling at the site of the tumor. Fever may also be present. The tumor often spreads (metastasis) to the lungs and other bones. According to the Bone Cancer Research Trust (BCRT), the most common symptoms are localized pain, swelling, and sporadic bone pain with variable intensity. The swelling is most likely to be visible if the sarcoma is located on a bone near the surface of the body, but when it occurs in other places deeper in the body, like on the pelvis, it may not be visible.

Diagnosis

The definitive diagnosis is based on histomorphologic findings, immunohistochemistry and molecular pathology.

Ewing's sarcoma is a small-blue-round-cell tumor that typically has a clear cytoplasm on H&E staining, due to glycogen. The presence of the glycogen can be demonstrated with positive PAS staining and negative PAS diastase staining. The characteristic immunostain is CD99, which diffusely marks the cell membrane. However, as CD99 is not specific for Ewing's sarcoma, several auxiliary immunohistochemical markers can be employed to support the histological diagnosis. A small round cell tumor that lacks morphologic, immunohistochemical, and electron microscopic evidence of neuroectodermal differentiation. It represents one of the two ends of the spectrum called ewing sarcoma/peripheral neuroectodermal tumor.

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

Magnetic resonance imaging slice showing Ewing's sarcoma of the left hip (white area shown right)

Techniques used diagnosis are Magnetic resonance imaging radiographs Computed axial tomography (CT)

Treatment

Almost all people receive multidrug chemotherapy (most often vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide) The surgical resection may involve limb salvage or amputation.Radiotherapy has been used for localized disease.The tumor has a unique property of being highly sensitive to radiation, sometimes acknowledged by the phrase "melting like snow", but the main drawback is that it recurs dramatically after some time. Antisense oligodeoxynucleotides have been proposed as possible treatment by down-regulating the expression of the oncogenic fusion protein associated with the development of Ewing's sarcoma resulting from the EWS-ETS gene translocation. In most pediatric cancers including sarcoma, proton beam radiation (also known as proton therapy) delivers an equally effective dose to the tumor with less damage to the surrounding normal tissue compared to photon radiation.

Treatment often includes chemotherapy, radiation therapy, surgery, and stem cell transplant. Targeted therapy and immunotherapy are being studied.

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Pazopanib (Brand name: Votrient)Advanced soft tissue sarcoma (STS) who have received prior chemotherapy.

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