Ewing sarcoma

ALSO KNOWN AS: Ewing’s sarcoma, Ewing sarcoma of the bone, extraosseous Ewing sarcoma, extraskeletal Ewing sarcoma, Ewing tumor, Ewing angioendothelioma, Ewing endothelial sarcoma, Ewing syndrome, malignant primary bone tumor, red bone marrow tumor, neural tumor

RELATED CONDITIONS: Primitive neuroectodermal tumor, peripheral primitive neuroectodermal tumor, Askin’s tumor, osteosarcoma

DEFINITION: Ewing sarcoma is a rare disease involving cancer cells found in bones and soft tissue. It usually occurs in the pelvis, ribs, arm bone (humerus), shoulder blade, or leg bone (femur). It gets its name from James Ewing, who, in the 1920s, first described the disease as being separate from other known types of cancers, such as lymphoma or neuroblastoma. Ewing noticed that this type of cancer responded well to radiation. It belongs to a group of tumors called the Ewing family of tumors because of the close molecular relationship between these kinds of tumors.

Risk factors: About 85 percent of people who develop this disease have an unusual rearrangement between chromosomes: A piece of chromosome 11 and a piece of chromosome 22 have switched places (called a gene translocation). However, this translocation is not inherited or passed on genetically, so family members of those affected with Ewing sarcoma do not have an increased risk of developing the cancer.

Male teenagers are most often diagnosed with this disease. The cancer is thought to be linked somehow to the rapid growth that occurs during puberty. White individuals are nine to ten times more likely to develop this disease than Asian and Black Americans. Very rarely, Ewing sarcoma can develop as a secondary tumor in patients who have had radiation therapy for another type of cancer.

Etiology and the disease process: Because this cancer occurs most often during the teenage years, there may be a link between the onset of puberty and the early stages of this disease. Ewing sarcoma usually starts in the pelvis or leg bones, though it can start in soft tissue. When tumor cells enter the bloodstream, tumors may spread to the chest cavity, other bones, bone marrow, lungs, kidneys, or heart. This disease may also spread to the central nervous system or lymph nodes, but this is much less common.

Incidence: This disease occurs most often in male children and teenagers between ten and fifteen. However, young females also develop this disease. People over the age of twenty-five rarely develop this type of cancer. Between 200 and 250 cases are diagnosed each year in the United States, accounting for about 1 percent of all childhood cancers.

Symptoms: Symptoms of Ewing sarcoma involve pain (which may be worse at night), swelling (especially when the tumor is in the long bones of the arm or leg), redness, tenderness, stiffness, a mass that grows quickly, and may feel warm, or a bone that breaks unexpectedly. Some patients have fever, fatigue, anemia, or weight loss. Numbness, tingling, or paralysis can also be symptoms if the tumor is near nerves.

Screening and diagnosis: No screening is recommended because this disease is so rare. When Ewing sarcoma is suspected, doctors generally use X-rays to determine if there is a suspicious growth. A magnetic resonance imaging (MRI) scan or blood tests also may help make a diagnosis. If Ewing sarcoma is suspected, a bone scan or a computed tomography (CT) scan, which usually includes the lungs to see if the disease has spread there, is used to see if the disease has spread.

Ewing sarcoma may initially be mistaken for a bone infection (osteomyelitis) or another type of bone cancer (osteomyelitis). A sample of the tumor (biopsy) is necessary to confirm the diagnosis of Ewing sarcoma. A biopsy may be performed with a fine needle, taking only a small sample of the tumor, or by surgery, where much of the tumor is removed. Sometimes, bone marrow is biopsied to determine if the disease has spread.

Staging for Ewing sarcoma follows the American Joint Committee on Cancer system for bone cancer, which is as follows:

• Stage IIA: The tumor is up to 8 centimeters wide. The cancer has not spread elsewhere within the body.
• Stage IIB: The tumor is wider than 8 centimeters. The cancer has not spread elsewhere within the body.
• Stage III: The tumor has spread to multiple sites within the same bone. The cancer has not spread elsewhere within the body.
• Stage IVA: The tumor (of any size) has metastasized to the lungs but not to the lymph nodes or other distant sites within the body.
• Stage IVB: The tumor (of any size) has metastasized to the lymph nodes or other distant sites, except the lungs.

Note that Ewing tumors are considered high-grade and thus always staged beyond stage I.

Treatment and therapy: Ewing sarcoma is usually a very aggressive disease. By the time of diagnosis, nearly all patients with Ewing sarcoma have some spreading of the disease throughout the body. Most patients are treated with chemotherapy, sometimes before and after surgery, to ensure treatment of any tumors throughout the body.

Surgery or radiation may be used at the site of the main tumor if it can be removed without damaging vital organs. Sometimes, surgery involves removing bones, which can be replaced or rebuilt with artificial bones or bone grafts. With Ewing sarcoma, radiation therapy usually involves radiation that comes from a machine outside the body rather than from implanted radiation seeds. Radiation therapy can shrink large tumors to alleviate symptoms if the tumor cannot be removed with surgery.

Other types of treatment may include rehabilitation, including occupational or physical therapy. Patients may also need supportive care to help with the side effects of chemotherapy, radiation, or surgery. Some patients may benefit from blood stem cells or bone marrow transplants.

Diagnosis of Ewing sarcoma usually occurs during the teenage years, sometimes an already turbulent period. Surgery may cause disfigurement during a period of life when looks are very important. Support groups in which teens meet other people with this condition may be especially helpful in dealing with the psychological trauma that this disease can cause.

Generally, patients with Ewing sarcoma benefit from treatment at a children’s hospital or medical center with doctors who have experience treating pediatric cancers.

Prognosis, prevention, and outcomes: The prognosis for patients with this disease depends on the primary tumor's spread, size and location, and how responsive they are to chemotherapy. Patients who, at diagnosis, show no signs of the spread of the disease and choose an aggressive course of treatment involving chemotherapy, surgery, and radiation have survival rates at five years, between 70 and 82 percent. However, at diagnosis, about one-quarter to one-third of these patients have widespread because symptoms are vague and nonspecific. These patients have a five-year survival rate of 39 percent. Children under ten, those with smaller tumors, those who respond well to chemotherapy, and those who have tumors below the elbow or the calf have the highest survival rates.

People who have had Ewing sarcoma need continual follow-up care. Even if the cancer is treated and its spread stopped, it often develops again in the place where it first arose and tends to spread throughout the body. Health issues may develop later due to treatment. These issues may involve heart and lung problems, slowed or decreased growth and development, and problems with sexual development. Monitoring is essential for patients who have this disease.

There is no known way to prevent Ewing sarcoma. However, not everyone with the gene translocation develops this disease. Scientists are investigating why gene translocation causes the disease in some people to see if there are ways to block this cancer from forming. Research is also underway to determine new and improved techniques for diagnosing this cancer earlier in the disease process.

Bibliography

Arndt, Carola A. S. Sarcomas of Bone and Soft Tissues in Children and Adolescents. Springer, 2021. 

"Ewing Family of Tumors." American Cancer Society, www.cancer.org/cancer/ewing-tumor. Accessed 20 July 2024.

"Ewing Sarcoma." Genetics Home Reference. US National Library of Medicine, June 2016, ghr.nlm.nih.gov/condition/ewing-sarcoma. Accessed 20 July 2024.

"Ewing Sarcoma." MedlinePlus, US National Library of Medicine, 25 Jan. 2022, medlineplus.gov/ency/article/001302.htm. Accessed 20 July 2024.

Grünewald, Thomas G. P., et al. "Ewing Sarcoma." Nature Reviews Disease Primers, vol. 4, no. 1, 2018, p. 5. doi.org/10.1038/s41572-018-0003-x.

Machado, Isidro, et al. "Biomarkers in the Ewing Sarcoma Family of Tumors." Current Biomarker Findings, vol. 4, 2014, pp. 81–91.

National Cancer Institute. "Ewing Sarcoma Treatment (PDQ)—Health Professional Version." National Institutes of Health, US Dept. of Health and Human Services, 19 Apr. 2024, www.cancer.gov/types/bone/hp/ewing-treatment-pdq. Accessed 20 July 2024.

Zöllner, Stefan K., et al. "Ewing Sarcoma—Diagnosis, Treatment, Clinical Challenges and Future Perspectives." Journal of Clinical Medicine, vol. 10, no. 8, 2021, p. 1685. doi.org/10.3390/jcm10081685.