Ewing sarcoma

by Bibianna Purgina, MD FRCPC
October 3, 2023


What is Ewing sarcoma?

Ewing sarcoma is a type of cancer. It is part of a category of diseases called Ewing family of tumours (EFTs) which also includes peripheral primitive neuroectodermal tumour (PNET). Ewing sarcoma typically occurs in teenagers and young adults. Ewing sarcoma is an aggressive cancer that often spreads from bone to the lungs.

About this article

This article was written by medical doctors in conjunction with patient advisers. It was designed to help patients read and understand their pathology report for Ewing sarcoma. The sections below explain many of the most common features found in pathology reports for this condition. If you have any questions about this article, please contact us.

Where in the body is Ewing sarcoma found?

The tumour can start in a bone or in the deep soft tissue such as muscle. The most common locations for Ewing sarcoma include the chest wall, lower limbs, and around the spine.

What genetic changes are found in Ewing sarcoma?

Ewing sarcoma typically shows a genetic change called a translocation involving a gene called EWSR1. A gene is a region of DNA that provides instructions for making a protein. DNA is stored on 46 chromosomes in each cell. Sometimes, a piece of DNA falls off one chromosome and becomes attached to a different chromosome. This is called translocation and it can result in the cell making a new and abnormal protein. If the new protein allows the cell to live longer than other cells or spread to other parts of the body, the cell can become a cancer.

How is this diagnosis made?

The first diagnosis of Ewing sarcoma is usually made after a small sample of the tumour is removed in a procedure called a biopsy. The biopsy tissue is then sent to a pathologist who examines it under a microscope.

What should you look for in your pathology report for Ewing sarcoma?

The information found in your pathology report for Ewing sarcoma will depend on the type of procedure performed. For example, the information found in a report after a biopsy is performed is usually limited to the diagnosis although some reports may also describe the results of additional tests such as immunohistochemistry (see section below).

After the entire tumour has been removed, your pathology report will include additional information such as the tumour size, tumour extension, presence or absence of lymphovascular and perineural invasion, and the assessment of margins. The results of any lymph nodes examined should also be included in this final report. This information is used to determine the cancer stage and to decide if additional treatment is required. These topics are described in more detail in the sections below.

What does Ewing sarcoma look like under the microscope?

When viewed under the microscope, Ewing sarcoma is made up of round cells that look blue because the nucleus of the cell (the part that contains the genetic information) is large compared to the cytoplasm (body of the cell). Pathologists describe cells that look like this as primitive and the tumour is sometimes called a small round blue cell tumour.

This picture shows a Ewing sarcoma made up of small round blood cells arranged in nests.
This picture shows a Ewing sarcoma made up of small round blood cells arranged in nests.

What other tests may be performed to confirm the diagnosis?

Additional tests such as immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), or next-generation sequencing (NGS) may usually performed to confirm the diagnosis and to look for changes in the EWSR1 gene.  When IHC is performed, the tumour cells are positive (reactive) for CD99. Specifically, CD99 should stain the outer wall (cell membrane) of the tumour cells. These tests can be done on the biopsy specimen or when the tumor has been surgically removed.

Why is the tumour size important?

After the entire tumour has been removed, your pathologist will measure it in three dimensions and the largest dimension will be described in your pathology report. The size of the tumour is important because it is used to determine the pathologic tumour stage (pT).

Is Ewing sarcoma graded?

By definition, all Ewing sarcoma’s are considered high grade tumours.

Has the tumour spread into surrounding tissues?

Most Ewing sarcomas start in deep sites such as bone, the chest wall, and around the muscles of the lower limb.  As the tumour grows, it can spread into or around neighboring muscles, bones, and blood vessels. Your pathologist will examine samples of the surrounding tissues under the microscope to look for cancer cells. Any surrounding organs or tissues that contain cancer cells will be described in your report.

What does treatment effect​ mean?

If you received chemotherapy and/or radiation therapy before the operation to remove the tumour, your pathologist will examine all the tissue sent to pathology to see how much of the tumour is still alive (viable). Most commonly, your pathologist will describe the percentage of tumour that is dead.

What does perineural invasion mean and why is it important?

Perineural invasion means that tumour cells were seen attached to a nerve. Nerves are found all over the body and they are responsible for sending information (such as temperature, pressure, and pain) between your body and your brain. Perineural invasion is important because tumour cells that have become attached to a nerve can spread into surrounding tissues by growing along the nerve. This increases the risk that the tumour will regrow after treatment.

Perineural invasion

What does lymphovascular invasion mean?

Lymphovascular invasion means that tumour cells were seen inside of a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. Lymphovascular invasion is important because tumour cells can use blood vessels or lymphatic vessels to spread to other body parts such as lymph nodes or the lungs.

Lymphovascular invasion

What is a margin?

A margin is any tissue that was cut by the surgeon to remove the tumour from your body. Depending on the type of surgery you have had, the margins can include bones, muscles, blood vessels, and nerves that were cut to remove the tumour from your body. Margins will only be described in your report after the entire tumour has been removed.

Tumour margin

All margins will be very closely examined under the microscope by your pathologist to determine the margin status.  A margin is considered ‘negative’ when there are no cancer cells at the edge of the cut tissue. A margin is considered ‘positive’ when there are cancer cells at the edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will recur in the same site after treatment (local recurrence).

What are lymph nodes​?

Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of cancer cells from the tumour to a lymph node is called metastasis.

Lymph node

Your pathologist will carefully examine each lymph node for cancer cells. Lymph nodes on the same side as the tumour are called ipsilateral while those on the opposite side of the tumour are called contralateral. Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative. The examination of lymph nodes is important because this information is used to determine the nodal stage (see Pathologic stage below).

How do pathologists determine the pathologic stage for Ewing sarcoma?

​The pathologic stage for Ewing sarcoma is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer. There are separate staging systems for Ewing sarcoma arising in bone and soft tissue. Tumours occurring in children are not staged using this system.

This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. Generally, a higher number means more advanced disease and a worse prognosis.

If the tumour started in bone, it is staged as follows:
Tumour stage (pT)

For bone cancers or sarcomas such as Ewing sarcoma, the primary tumour (T) stage depends on where the tumour was located in your body.

​If the tumour was located in your appendicular skeleton (these are bones of your appendages, and include the arms, legs, shoulder, trunk, skull, and facial bones), it is given a tumour stage from 1-3 based on tumour size whether there a separate tumor nodule(s).

  • pT1: Tumor ≤ 8 cm in greatest dimension.
  • pT2: Tumor > 8 cm in greatest dimension.
  • pT3: Discontinuous tumors in the primary bone site.

If the tumour was located in your spine, it is given a tumour stage from 1-4 based on the extent of tumor growth.

  • pT1: Tumor confined to one vertebral segment or two adjacent vertebral segments.
  • pT2: Tumor confined to three adjacent vertebral segments.
  • pT3: Tumor confined to four or more adjacent vertebral segments, or any nonadjacent vertebral segments.
  • pT4: Extension into the spinal canal or great vessels.

If the tumour was located in your pelvis, it is given a tumour stage from 1-4 based on the size of the tumour and the extent of tumor growth.

  • pT1: Tumor confined to one pelvic segment with no extraosseous (growing outside of the bone) extension.
    • pT1a: Tumor ≤ 8 cm in greatest dimension.
    • pT1b: Tumor >8 cm in greatest dimension.
  • pT2: Tumor confined to one pelvic segment with extraosseous extension or two segments without extraosseous extension.
    • pT2a: Tumor ≤ 8 cm in greatest dimension.
    • pT2b: Tumor >8 cm in greatest dimension.
  • pT3: Tumor spanning two pelvic segments with extraosseous extension.
    • pT3a: Tumor ≤ 8 cm in greatest dimension.
    • pT3b: Tumor >8 cm in greatest dimension.
  • pT4: Tumor spanning three pelvic segments or crossing the sacroiliac joint.
    • pT4a: Tumor involves sacroiliac joint and extends medially to the sacral neuroforamen (space where the nerves pass through).
    • pT4b: Tumor encasement of external iliac vessels or presence of gross tumor thrombus in major pelvic vessel.

If after microscopic examination, no tumour is seen in the resection specimen sent to pathology for examination, it is given the tumour stage pT0 which means there is no evidence of primary tumour.

If your pathologist cannot reliably evaluate the tumor size or the extent of growth, it is given the tumour stage pTX (primary tumour cannot be assessed).  This may happen if the tumour is received as multiple small fragments.

Nodal stage (pN)

Primary bone cancers or sarcomas such as Ewing sarcoma are given a nodal stage of 0 or 1 based on the presence or absence of cancer cells in one or more lymph nodes.

If no cancer cells are seen in any lymph nodes, the nodal stage is N0. If no lymph nodes are sent for pathological examination, the nodal stage cannot be determined, and the nodal stage is listed as NX.  If cancer cells are found in any lymph nodes, then the nodal stage is listed as N1.

Metastasis stage (pM)

Bone sarcomas such as Ewing sarcoma are given a metastasis stage only if the presence of metastasis has been confirmed by a pathologist.  There are two metastasis stages in primary bone sarcomas such as Ewing sarcoma, M1a and M1b.  If there are confirmed lung metastasis, then the tumor metastatic stage is 1a.

The metastasis stage can only be given if tissue from a distant site is sent for pathological examination. Because this tissue is rarely present, the metastasis stage cannot be determined, and it is typically not included in your report.

If the tumour developed in soft tissue such as muscle or fat, it is staged as follows:
Tumour stage (pT)

The tumour stage for Ewing sarcoma varies based on the body part involved. For example, a 5-centimeter tumour that starts in the head will be given a different tumour stage than a tumour that starts deep in the back of the abdomen (the retroperitoneum). However, in most body sites, the tumour stage includes the tumour size and whether the tumour has grown into surrounding body parts.

Tumour stage for tumours starting in the head and neck:
  • T1 – The tumour is no greater than 2 centimeters in size.
  • T2 – The tumour is between 2 and 4 centimeters in size.
  • T3 – The tumour is greater than 4 centimeters in size.
  • T4 – The tumour has grown into surrounding tissues such as the bones of the face or skull, the eye, the larger blood vessels in the neck, or the brain.
Tumour stage for tumours starting on the outside of the chest, back, or stomach and the arms or legs (trunk and extremities):
  • T1 – The tumour is no greater than 5 centimeters in size.
  • T2 – The tumour is between 5 and 10 centimeters in size.
  • T3 – The tumour is between 10 and 15 centimeters in size.
  • T4 – The tumour is greater than 15 centimeters in size.
Tumour stage for tumours starting in the abdomen and organs inside the chest (thoracic visceral organs):
  • T1 – The tumour is only seen in one organ.
  • T2 – The tumour has grown into the connective tissue that surrounds the organ from which is started.
  • T3 – The tumour has grown into at least one other organ.
  • T4 – Multiple tumours are found.
Tumour stage for tumours starting in the space at the very back of the abdominal cavity (retroperitoneum):
  • T1 – The tumour is no greater than 5 centimeters in size.
  • T2 – The tumour is between 5 and 10 centimeters in size.
  • T3 – The tumour is between 10 and 15 centimeters in size.
  • T4 – The tumour is greater than 15 centimeters in size.
Tumour stage for tumours starting in the space around the eye (orbit):
  • T1 – The tumour is no greater than 2 centimeters in size.
  • T2 – The tumour is greater than 2 centimeters in size but has not grown into the bones surrounding the eye.
  • T3 – The tumour has grown into the bones surrounding the eye or other bones of the skull.
  • T4 – The tumour has grown into the eye (the globe) or the surrounding tissues such as the eyelids, sinuses, or brain.

If after microscopic examination, no tumour is seen in the resection specimen sent to pathology for examination, it is given the tumour stage pT0 which means there is no evidence of primary tumour.

If your pathologist cannot reliably evaluate the tumor size or the extent of growth, it is given the tumour stage pTX (primary tumour cannot be assessed).  This may happen if the tumour is received as multiple small fragments.

Nodal stage (pN)

Ewing sarcomas are given a nodal stage of 0 or 1 based on the presence or absence of cancer cells in one or more lymph nodes.

If no cancer cells are seen in any lymph nodes, the nodal stage is N0. If no lymph nodes are sent for pathological examination, the nodal stage cannot be determined, and the nodal stage is listed as NX.  If cancer cells are found in any lymph nodes, then the nodal stage is listed as N1.

Metastasis stage (pM)

Ewing sarcomas are given a metastasis stage only if the presence of metastasis has been confirmed by a pathologist.  There are two metastasis stages in primary bone sarcomas such as EFT, M1a and M1b.  If there are confirmed lung metastasis, then the tumor metastatic stage is 1a.

The metastasis stage can only be given if tissue from a distant site is sent for pathological examination. Because this tissue is rarely present, the metastasis stage cannot be determined, and it is typically not included in your report.

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