Extra-osseous Ewing’s Sarcoma

Extraosseous Ewing sarcoma, EES, Extraosseous Ewing tumor, EOE, Extraskeletal Ewing sarcoma

Extra-osseous Ewing’s sarcoma is a rare and aggressive cancer that begins in the soft tissues around bones rather than in the bones themselves. While most Ewing sarcomas start in bones, this form affects muscles, tendons, ligaments, and sometimes even internal organs, requiring specialized diagnosis and treatment approaches.

Table of contents

• What Is Extra-osseous Ewing’s Sarcoma?
• Where Does It Occur?
• Who Is Affected?
• Signs and Symptoms
• What Causes This Condition?
• How Doctors Diagnose Extra-osseous Ewing’s Sarcoma
• Treatment Approaches
• Outlook and Long-Term Considerations

What Is Extra-osseous Ewing’s Sarcoma?

Extra-osseous Ewing’s sarcoma is a type of cancer that develops in the soft tissues surrounding bones rather than in the bones themselves^[1]. It belongs to a family of cancers called the Ewing sarcoma family of tumors, which are cancers that look similar under a microscope and are made up of small round blue cells^[4].

This condition is closely related to Ewing sarcoma of the bone, which is the more common form. Both types share similar characteristics and genetic changes, but they differ in where they begin growing in the body^[3]. Extra-osseous Ewing’s sarcoma affects soft tissues, which include muscles, tendons, and ligaments that connect, support, and surround other body parts and organs^[11].

Although Ewing sarcoma is already rare, accounting for less than 1% of all childhood cancers, the extra-osseous form is even less common^[4]. Doctors have identified extra-osseous Ewing sarcoma as one of several types within the Ewing family of tumors^[17].

Where Does It Occur?

Extra-osseous Ewing’s sarcoma most commonly develops in specific areas of the body. The paravertebral spaces (areas near the spine), lower extremities, head and neck, and pelvis are the most frequently affected sites^[1].

However, this cancer can also appear in other, less common locations throughout the body. These rare sites include the retroperitoneum (the space behind the abdominal cavity), omentum (a fold of tissue in the abdomen), orbit (the eye socket), skin, and chest wall^[1]. In very rare cases, extra-osseous Ewing sarcoma has been found in solid organs such as the pancreas^[7].

When extra-osseous Ewing sarcoma occurs in the chest wall, it may be referred to as an Askin tumor^[17]. Unlike bone-based Ewing sarcomas, the extra-osseous form is more likely to arise from areas along the central axis of the body and less likely to start in the pelvis^[1].

Who Is Affected?

Extra-osseous Ewing’s sarcoma typically affects children and young adults, with most cases occurring in people between the ages of 10 and 20 years^[3]. The condition can also affect younger children and people in their late 20s to early 30s^[3].

Patients with extra-osseous Ewing sarcoma tend to have different characteristics compared to those with bone-based Ewing sarcoma. People with the extra-osseous form are generally older on average and are less likely to be male or White compared to patients with skeletal tumors^[1].

Ewing sarcoma in general is slightly more common in males than females. The disease is more likely to affect people who are White (Hispanic or non-Hispanic) than people who are Asian American or Black^[3].

Signs and Symptoms

The symptoms of extra-osseous Ewing’s sarcoma depend mainly on where the tumor is located in the body^[1]. Because this cancer can develop in various soft tissue locations, the symptoms can vary considerably from person to person.

Common symptoms may include pain at the site of the tumor, which can come and go and may worsen at night^[3]. Swelling or a lump may appear in the affected area. These lumps may feel soft or warm to the touch^[17].

When the tumor is located near the spine, symptoms might include back pain, weakness in the arms or legs, numbness, or even paralysis caused by the tumor pressing on nerves^[3]. If the tumor develops in the chest wall, a person may experience cough, shortness of breath, or chest pain^[4].

Some people with extra-osseous Ewing’s sarcoma may experience symptoms that affect the whole body, including fever that doesn’t go away, losing weight without trying, and fatigue^[2]. However, the tumor may be present for many months before it becomes large enough to cause noticeable symptoms^[4].

What Causes This Condition?

The exact cause of extra-osseous Ewing’s sarcoma is not known. The cancer develops when changes occur in a cell’s genetic material^[17]. In Ewing sarcoma cells, a genetic mutation (change) happens after a person is born, involving specific genes called EWSR1 and FLI1. These two genes fuse together to create a new gene that causes cells to multiply and create cancerous tumors^[3].

This genetic abnormality is not inherited from a child’s parents. The chromosomal changes occur after birth, and researchers do not understand why this abnormality occurs^[17]. Studies have shown that extra-osseous Ewing sarcoma shares the same genetic abnormality, the EWSR1 gene rearrangement, with other members of the Ewing sarcoma family of tumors^[7].

Importantly, researchers have ruled out exposure to substances that cause cancer as a trigger for Ewing sarcoma. This is because the condition typically affects children and young adults who have not experienced long-term exposure to cancer-causing substances^[3].

Doctors have not identified any specific risk factors that make one person more at risk than another. The tumor does not develop as a result of any dietary, social, or behavioral habits. There are no known ways to prevent the disease, and patients or their parents should know that there is nothing they could have done differently to prevent these tumors^[17].

How Doctors Diagnose Extra-osseous Ewing’s Sarcoma

Diagnosing extra-osseous Ewing’s sarcoma requires several different tests and procedures. Healthcare providers will start with a physical examination, feeling for any lumps or bumps and asking about symptoms^[3].

The available diagnostic tools include ultrasonographic evaluation, computed tomography (CT), and magnetic resonance imaging (MRI)^[1]. Imaging tests allow providers to take a closer look at soft tissues. Common tests include CT scans, MRI scans, PET scans, and bone scans^[3].

A biopsy is essential for confirming the diagnosis. During a biopsy, doctors remove a small sample of tissue from the tumor to examine it under a microscope^[1]. The tissue then undergoes histopathologic and immunohistochemical examination, which means specialists look at the tissue structure and use special tests to identify specific proteins and markers in the cells^[1].

Several histologic and genetic biomarkers have been established to help identify extra-osseous Ewing’s sarcoma, although their use needs to be further tested by larger studies^[1]. Under the microscope, extra-osseous Ewing sarcoma appears as small round blue cells, similar to other tumors in the Ewing family^[4].

Treatment Approaches

Extra-osseous Ewing’s sarcoma requires multimodality therapeutic strategies, meaning treatment typically involves a combination of different approaches^[1]. The main treatment methods include surgery, chemotherapy, and sometimes radiation therapy.

For localized disease (cancer that has not spread), the recommended treatment is surgery^[1]. However, chemotherapy is usually added to achieve improved survival. Neoadjuvant chemotherapy (chemotherapy given before surgery) has shown more promising results than adjuvant chemotherapy (chemotherapy given after surgery)^[1].

A typical treatment plan often begins with chemotherapy for 8 to 12 weeks. Doctors then evaluate the tumor with a CT or MRI scan. Depending on the tumor size and location, patients may need surgery or radiation therapy. After surgery or radiation, chemotherapy usually continues for several more months^[14].

Radiotherapy is an option to achieve local control of the cancer, although its complications have reduced its use in some cases^[1]. For metastatic or recurrent disease (cancer that has spread or come back), systematic chemotherapy improves survival^[1].

Treatment requires a team approach involving multiple specialists. The team typically includes a cancer specialist (oncologist), an orthopedic surgeon who operates on bones, and a radiation oncologist who works with radiation to kill cancer cells^[14].

Outlook and Long-Term Considerations

Patient characteristics and outcomes appear to be different in extra-osseous Ewing sarcoma compared to patients with skeletal Ewing sarcoma, with implications for patient care and prognosis^[1]. Extra-osseous Ewing sarcoma is characterized by its aggressive nature and predilection for soft tissue sites^[7].

The cancer shows aggressive clinical behavior with a high rate of local recurrence (cancer coming back in the same area) and distant metastasis (cancer spreading to other parts of the body)^[1]. The prognosis can be unfavorable due to late-stage diagnosis and frequent recurrence and metastasis^[7].

Young people who undergo treatment for Ewing sarcoma may experience late effects, which are health issues that develop months or years after completing treatment^[2]. Cancer and cancer treatment may lead to issues affecting organs and tissues, growth and development, moods and mental health, the ability to think and remember information, and the ability to have children^[3].

Because of these potential long-term effects, healthcare professionals often suggest long-term monitoring for side effects after treatment^[2]. Regular follow-up care is essential for managing any complications and ensuring the best possible quality of life for survivors.