Your pathology report for Ewing sarcoma

by Bibianna Purgina, MD FRCPC
January 2, 2026

---

Ewing sarcoma is a rare and aggressive type of cancer that most often affects bones and, less commonly, the soft tissues. It belongs to a group of tumours called sarcomas, which arise from connective tissues such as bone, muscle, or soft tissue. Ewing sarcoma is made up of very immature-appearing cells and is driven by a specific genetic change that causes abnormal cell growth.

This tumour most often occurs in children, adolescents, and young adults, and early diagnosis is important because prompt treatment can significantly improve outcomes.

Where does Ewing sarcoma develop?

Ewing sarcoma most commonly develops in the long bones, such as the thigh bone (femur), shin bone (tibia), and upper arm bone (humerus). It also frequently involves the pelvis and ribs. Within bones, the tumour usually arises in the shaft (diaphysis) or the area between the shaft and the end of the bone.

In about 10–15% of cases, Ewing sarcoma develops outside the bones in the soft tissues. This is called extraskeletal Ewing sarcoma and can occur in many different locations throughout the body.

What are the symptoms of Ewing sarcoma?

The most common symptoms are localized pain and swelling at the site of the tumour. The pain may worsen over time and can be mistaken for an injury, especially in children and teenagers.

Some patients develop a palpable mass, and in more advanced cases, the tumour may weaken the bone, leading to a pathological fracture. Fever and fatigue can occur, particularly as the disease advances or spreads.

About one quarter of patients have metastatic disease at the time of diagnosis, meaning the cancer has already spread to other parts of the body. When this happens, symptoms may relate to the affected organs, most commonly the lungs.

Who gets Ewing sarcoma?

Ewing sarcoma is the second most common malignant bone tumour in children and young adults, after osteosarcoma. Nearly 80% of patients are under 20 years of age, with the highest incidence during the teenage years. It is less common in adults over 30, and when present, the tumour more often arises in soft tissue than in bone.

The disease is slightly more common in males than in females. Ewing sarcoma is rare in individuals of African ancestry, likely due to genetic factors.

What causes Ewing sarcoma?

Most cases of Ewing sarcoma occur sporadically, meaning they develop by chance and are not inherited.

A genetic rearrangement inside the cancer cells causes the tumour. A genetic rearrangement occurs when pieces of DNA break and reattach incorrectly. In Ewing sarcoma, this creates an abnormal fusion gene that joins two genes together. The most common fusion involves the EWSR1 gene and the FLI1 gene.

This fusion gene produces an abnormal protein that acts as a powerful switch, turning many growth-related genes on or off at the wrong time. This disrupts normal cell development and drives tumour formation. Additional genetic changes may also be present and can influence how aggressive the tumour is.

How is the diagnosis made?

The diagnosis of Ewing sarcoma is based on a combination of imaging, microscopic examination, immunohistochemistry, and molecular testing.

Imaging

X-rays often show a poorly defined area of bone destruction with a characteristic layered reaction of the surrounding bone, sometimes described as an “onion-skin” appearance. CT, MRI, and PET scans are used to determine the size of the tumour, its extension into nearby soft tissue, and whether the cancer has spread.

Microscopic (pathologic) features

When examined under the microscope, Ewing sarcoma consists of small, round cells that appear very immature. The cells are usually uniform, with round nuclei, finely textured chromatin, and little visible cytoplasm. The borders between cells are indistinct, giving the tumour a densely packed appearance.

In some cases, the tumour cells are slightly larger and show more variation in shape and nuclear features. Rarely, the cells may show partial nerve-like differentiation, forming small groups oriented around a central space. After chemotherapy, areas of tumour cell death are common and may be replaced by scar-like tissue.

Immunohistochemistry

Immunohistochemistry uses special stains to detect proteins produced by tumour cells.

Most Ewing sarcomas show strong, diffuse CD99 staining along the cell membrane. While this finding is very sensitive, it is not entirely specific, so additional markers are often used. A protein called NKX2-2 is commonly positive and is more specific for Ewing sarcoma.

Some tumours express keratins or nerve-related markers, but these findings vary and are not required for diagnosis.

Molecular testing

Genetic confirmation is often required to make a definitive diagnosis of Ewing sarcoma.

In about 85% of cases, the tumour shows a fusion between EWSR1 and FLI1. Another 10% show a fusion between EWSR1 and ERG. All cases of Ewing sarcoma have a fusion involving a member of the FET gene family (usually EWSR1) and a member of the ETS family of transcription factors.

Detecting one of these fusions confirms the diagnosis and helps distinguish Ewing sarcoma from other small round cell tumours.

What does treatment response mean?

Treatment response describes how much of the tumour was destroyed by treatment, most often chemotherapy given before surgery. In Ewing sarcoma, chemotherapy is a critical part of care, and evaluating how the tumour responded is very important.

After surgery, the pathologist examines the removed tumour under the microscope to determine how much of it is necrotic, meaning the tumour cells are dead and have been replaced by scar-like tissue.

• A good treatment response means there is 100% tumour necrosis, with no viable (living) tumour cells remaining in the specimen.

• A poor treatment response means that viable tumour cells remain, even if most of the tumour shows treatment-related damage.

This distinction is important because patients whose tumours show complete tumour necrosis tend to have a better prognosis. In contrast, the presence of any living tumour cells is associated with a higher risk of recurrence.

Treatment response does not change the diagnosis, but it helps doctors:

• Estimate the risk of the cancer coming back

• Decide whether additional treatment may be needed

• Plan follow-up care and surveillance

Your pathology report may describe treatment response using phrases such as complete tumour necrosis or residual viable tumour. Your healthcare team will explain what these findings mean for your individual situation.

Do pathologists grade Ewing sarcoma?

Unlike many other cancers, Ewing sarcoma is not graded by pathologists. Tumour grade is usually based on how closely cancer cells resemble normal cells, but Ewing sarcoma cells are uniformly high grade by definition. This means the tumour cells already look very abnormal and grow aggressively, regardless of subtle differences under the microscope.

Because of this, prognosis and treatment decisions for Ewing sarcoma are based on other factors, such as:

• Whether the cancer has spread at diagnosis.

• How large the tumour is and where it is located.

• How well the tumour responds to chemotherapy.

What does perineural invasion mean?

Perineural invasion (PNI) means that cancer cells are found around or along a nerve. Nerves can act as pathways that allow tumour cells to spread into nearby tissues.

Perineural invasion is uncommon in Ewing sarcoma. When present, it suggests more locally aggressive tumour behaviour, but it does not, by itself, mean the cancer has spread to distant organs. Pathologists report this feature because it may influence decisions about local treatment, such as surgery or radiation.

What does lymphovascular invasion mean?

Lymphovascular invasion (LVI) means that cancer cells are found inside small blood vessels or lymphatic channels. These vessels are part of the body’s circulation system and can provide a route for cancer cells to spread.

In Ewing sarcoma, lymphovascular invasion is not commonly identified, but when present, it may indicate a higher risk of tumour spread. Its presence is noted in the pathology report to help doctors assess overall risk and plan follow-up care.

What are margins, and why are they important?

Margins describe the edges of the tissue removed during surgery. After the tumour is removed, a pathologist examines the margins to see whether any cancer cells are present at the cut edges.

• A negative margin means no tumour cells are seen at the edge of the specimen, suggesting the tumour was removed entirely.

• A positive margin means tumour cells are present at the edge, indicating that some cancer may remain in the body.

In Ewing sarcoma, achieving negative margins is important because it lowers the risk of local recurrence. Margin status helps guide decisions about additional treatment, such as radiation therapy, and influences long-term follow-up planning.

How is Ewing sarcoma staged?

Ewing sarcoma is staged using standard cancer staging systems that consider:

• Tumour size and location.

• Involvement of nearby structures.

• Spread to lymph nodes.

• Presence of distant metastases.

The lungs are the most common site of metastatic disease.

What happens after the diagnosis?

After Ewing sarcoma is diagnosed, additional tests are performed to determine the stage of the disease and to guide treatment planning. These tests usually include imaging studies of the lungs and other parts of the body to detect metastatic disease, since the lungs are the most common site of metastasis.

Treatment typically involves a multimodal approach, which means using more than one type of therapy. This usually includes chemotherapy, combined with surgery and/or radiation therapy to treat the primary tumour. Chemotherapy is often given first to shrink the tumour and treat any microscopic spread before local treatment.

Patients are usually cared for by a specialized sarcoma team, often at a cancer centre with experience treating Ewing sarcoma. After treatment, regular follow-up with imaging and clinical exams is essential to monitor for recurrence or late treatment effects.

What is the prognosis for a person with Ewing sarcoma?

The outlook for Ewing sarcoma has improved significantly with modern treatment. For patients with localized disease, long-term cure rates are approximately 65–70%.

When the cancer has spread at diagnosis or returns early after treatment, the prognosis is less favourable, with long-term survival rates below 30%. Tumours arising in specific locations, such as the pelvis, tend to have a worse outcome.

A complete response to chemotherapy before surgery is associated with a better prognosis.

Questions to ask your doctor

• Where is my tumour located, and has it spread?
• Was genetic testing performed to confirm the diagnosis?
• What treatment options are available for my stage of disease?
• How will treatment affect my daily life and long-term health?
• What follow-up tests will I need after treatment?