Epidemiology

Ewing sarcoma is a rare type of cancer, making it particularly challenging to study and treat. It affects approximately 200 to 300 new patients each year in the United States, representing less than one percent of all childhood cancers.^[5] The disease accounts for around 10 to 15 percent of all bone sarcomas and is the second most common bone cancer in children and young adults.^[3] In the United States, the incidence is about 1.5 per million in the adolescent and young adult population, with approximately 1.7 children out of every 1 million developing the disease among those younger than 15 years.^[6][10]

The cancer predominantly affects adolescents and young adults, with a peak occurrence between the ages of 10 and 20 years.^[1][2] Most people receive their diagnosis around age 15.^[2] However, Ewing sarcoma can also appear in younger children as well as in people in their late twenties to early thirties.^[2] The disease is slightly more common in males than in females.^[2][4] There are also notable differences across racial and ethnic groups. Ewing sarcoma is more likely to affect people who are white, both Hispanic and non-Hispanic, compared to those who are Asian American or Black.^[2][4] It is quite rare in African Americans.^[4]

Causes

The exact cause of Ewing sarcoma remains unknown, but researchers have identified that it results from a genetic change that occurs after birth, not before. This means that the condition is not inherited from parents.^[5] The cancer develops due to a genetic mutation, which is a change in the structure or sequence of a gene, involving two specific genes: the EWSR1 gene and the FLI1 gene.^[2][8]

In about 85 percent of cases, these two genes fuse together through a process called a chromosomal translocation, which means parts of two different chromosomes swap places. This fusion creates a new, abnormal gene called EWS-FLI1.^[3][8] In the remaining 10 to 15 percent of cases, the EWSR1 gene fuses with other genes, such as the ERG gene.^[3] This newly formed gene behaves like a faulty switch, instructing cells to multiply uncontrollably and form cancerous tumors.

Researchers do not know what triggers this genetic change. Importantly, they have ruled out exposure to cancer-causing substances, known as carcinogens, as a factor. This is because Ewing sarcoma typically affects children and young adults who have not had long-term exposure to harmful chemicals or environmental toxins that are known to cause other types of cancer.^[2] The chromosomal changes happen randomly, not as a result of lifestyle, diet, or behavior.^[5]

Risk Factors

A risk factor is something that increases a person’s likelihood of developing a disease. For Ewing sarcoma, only a few risk factors have been identified, and none of them are within a person’s control. There are no known dietary habits, lifestyle choices, or environmental exposures that increase the risk of developing this cancer.^[5]

Age is the most significant risk factor. Ewing sarcoma most commonly occurs in teenagers and young adults between the ages of 10 and 20, although anyone can develop the disease.^[2][4] Males are at slightly higher risk than females.^[2] Race and ethnicity also play a role. People who are white, whether Hispanic or non-Hispanic, have the highest risk for Ewing sarcoma compared to other racial groups in the United States. The disease is much less common in Asian Americans and is rare in African Americans.^[2][4]

While Ewing sarcoma does not appear to be strongly linked to known hereditary cancer syndromes, accumulating evidence suggests there may be an inherited risk factor involving multiple chromosome locations associated with susceptibility to the disease.^[4] Some cases are associated with a germline mutation, which is a genetic change present in all cells of the body from birth, but this is not common.^[4] It is important for patients and their families to understand that there is nothing they could have done differently to prevent the tumor from forming.^[5]

Symptoms

The symptoms of Ewing sarcoma depend on where the tumor is located in the body and how large it has grown. The most common symptom is bone pain that seems to come and go but gradually becomes worse over time. This pain often gets more intense at night and can be mistaken for growing pains or a sports injury, especially in active children and teenagers.^[1][2][5]

Many people with Ewing sarcoma notice a lump or swelling near the affected bone. This swelling may appear on the arms, legs, chest, or other areas where the tumor is located. The lump may feel warm and soft to the touch.^[2][5] Sometimes the area around the tumor becomes tender, and it may hurt when pressure is applied.^[1][5]

A fever that does not go away is another symptom that can occur with Ewing sarcoma.^[1][2] In some cases, a bone fracture can happen without any injury. This is called a pathologic fracture, and it occurs because the tumor has weakened the bone.^[2][4] About 10 to 15 percent of patients present with such fractures at the time of diagnosis.^[4]

If the cancer spreads to other parts of the body, additional symptoms may appear. These can include tiredness, also known as fatigue, and unexpected weight loss.^[1][2] In about 25 to 30 percent of cases, the cancer has already spread to other parts of the body at the time of diagnosis, most commonly to the lungs, other bones, or bone marrow.^[3][4]

Because many of these symptoms can be caused by other, more common health problems, it is important to see a healthcare provider if any of these signs persist or cause concern. Only a healthcare professional can determine whether symptoms are due to Ewing sarcoma or another condition.^[1]

Prevention

Currently, there is no known way to prevent Ewing sarcoma. Because the disease is caused by random genetic changes that occur after birth and is not linked to environmental exposures, lifestyle factors, or inherited genetic conditions in most cases, there are no specific steps individuals can take to reduce their risk.^[5]

There are also no screening tests available to detect Ewing sarcoma in people who do not have symptoms. Screening tests are typically used to look for diseases in healthy people before symptoms appear, but no such tests exist for Ewing sarcoma.^[5]

The most important preventive measure is awareness. Parents, caregivers, and young adults should be alert to persistent bone pain, unexplained swelling, lumps, or fevers that do not go away. Early recognition and prompt medical evaluation can lead to earlier diagnosis and treatment, which are crucial for improving outcomes. If ongoing symptoms cause concern, it is important to seek medical attention from a healthcare provider.^[1]

Pathophysiology

Pathophysiology refers to the changes in the normal functioning of the body that occur when a disease is present. In the case of Ewing sarcoma, understanding these changes helps explain how the cancer develops and affects the body.

Ewing sarcoma begins when normal cells undergo a genetic change. The most common change involves a translocation between chromosomes 11 and 22. During this process, parts of these two chromosomes break off and swap places. This creates a new, abnormal gene called EWS-FLI1, which is present in about 85 percent of Ewing sarcoma cases.^[3][8] In the remaining cases, the EWSR1 gene may fuse with other genes like ERG.^[3]

The newly formed fusion gene acts as an abnormal transcription factor, which is a protein that controls the activity of other genes. This faulty transcription factor sends incorrect signals to cells, causing them to grow and divide in an uncontrolled manner. Instead of maturing into healthy cells, these cells remain immature and multiply rapidly, forming a tumor.^[3]

Ewing sarcoma most often develops in the bones, particularly in the long bones of the legs and arms, the pelvis, the ribs, and the spine. The tumor can also form in the soft tissues surrounding the bones, such as muscles, tendons, and ligaments.^[1][2] Tumors often develop during puberty when bones are growing rapidly.^[2]

As the tumor grows, it can weaken the bone, making it more prone to fractures. The cancer can also spread, or metastasize, to other parts of the body. The lungs, other bones, and bone marrow are the most common sites where Ewing sarcoma spreads.^[3][4] In some cases, the cancer may already have spread to distant locations at the time of diagnosis, even if it cannot be detected by imaging tests. This is referred to as subclinical metastatic disease.^[3]

The tumor itself can cause pain, swelling, and inflammation in the affected area. When Ewing sarcoma occurs in certain locations, such as the chest wall or spine, it can compress nearby organs or nerves, leading to additional complications like difficulty breathing or nerve damage.^[4]