Epithelioid sarcoma

by Jason Wasserman MD PhD FRCPC and Bibianna Purgina MD FRCPC
August 24, 2023


What is epithelioid sarcoma?

Epithelioid sarcoma is a type of soft tissue cancer. It is called epithelioid because the tumour cells look and behave in a manner similar to epithelial cells that are normally found on the outside or inside surface of any organ.

Where is epithelioid sarcoma normally found in the body?

Although epithelioid sarcoma can occur almost anywhere in the body, the most common location is the hand.

What causes epithelioid sarcoma?

The cause of epithelioid sarcoma is currently unknown and there are no genetic syndromes associated with this type of cancer.

What are the symptoms of epithelioid sarcoma?

The symptoms of epithelioid sarcoma typically include a painless, slow-growing mass just under the skin. Over time an ulcer may develop in the overlying skin. Tumours in deep locations may not cause any symptoms until the tumour is very large or cells have spread to nearby lymph nodes.

Can the cells in epithelioid sarcoma spread to other parts of the body?

Yes. The tumour cells in epithelioid sarcoma can spread to other parts of the body including lymph nodes, the lungs, and bone.

What are the types of epithelioid sarcoma?

There are two types of epithelioid sarcoma: classic or distal type and proximal or large cell type. The classic (distal) type usually involves the hands or feet while the proximal (large cell) type involves the deep tissue of the chest, abdomen, or pelvis.

How is this diagnosis made?

The diagnosis of epithelioid sarcoma can only be made after tissue from the tumour is examined under a microscope by a pathologist.

What does epithelioid sarcoma look like under the microscope?

Classic (distal) type epithelioid sarcoma is made up of epithelioid and spindle cells arranged in groups called nodules. A type of cell death called necrosis is often seen in the centre of the nodule. The nodules of tumour cells can be mistaken for a necrotizing granuloma, a type of inflammation seen in infections. The cytoplasm (body) of the tumour cells is filled with eosinophilic material which gives the cells a pink look under the microscope.

Proximal (large cell) epithelioid sarcoma is also made up of epithelioid and spindle cells arranged in multiple nodules or large groups called sheets. In contrast to the classic type, the proximal type is less likely to be confused for a necrotizing granuloma.

Epithelioid sarcoma
Epithelioid sarcoma. This picture shows a tumour made up predominantly of pink epithelioid cells.

What other tests may be ordered to confirm the diagnosis?

Pathologists typically perform a test called immunohistochemistry (IHC) to confirm the diagnosis and to rule out other conditions that can look very similar to epithelioid sarcoma under the microscope. When immunohistochemistry is performed, the tumour cells are typically positive for epithelial markers including low- and high-molecular-weight cytokeratins, cytokeratin 8/18, and cytokeratin 9/19. Unlike real epithelial cells, the tumour cells in epithelioid sarcoma are also positive for CD34. Importantly, the tumour cells in epithelioid sarcoma show a loss of normal SMARCB1 (also known as INI1) protein expression and this loss allows the tumour cells to grow and divide in an uncontrolled manner.

What grade is epithelioid sarcoma?

By definition, all epithelioid sarcomas are considered high grade tumours.

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 was still alive at the time it was removed from the body. Pathologists use the term viable to describe tissue that was still alive at the time it was removed from the body. In contrast, pathologists use the term non-viable to describe tissue that was not alive at the time it was removed from the body. Most commonly, your pathologist will describe the percentage of tumours that is non-viable.

What does perineural invasion mean and why is it important?

Perineural invasion is a term pathologists use to describe cancer cells attached to or inside a nerve. A similar term, intraneural invasion, is used to describe cancer cells inside a nerve. Nerves are like long wires made up of groups of cells called neurons. 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 the cancer cells can use the nerve to spread into surrounding organs and tissues. This increases the risk that the tumour will regrow after surgery.

perineural invasion

What does lymphovascular invasion mean and why is it important?

Lymphovascular invasion means that cancer cells were seen inside 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. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs.

lymphovascular invasion

What is a margin and why are margins important?

In pathology, a margin is the edge of a tissue that is cut when removing a tumour from the body. The margins described in a pathology report are very important because they tell you if the entire tumour was removed or if some of the tumour was left behind. The margin status will determine what (if any) additional treatment you may require.

Most pathology reports only describe margins after a surgical procedure called an excision or resection has been performed for the purpose of removing the entire tumour. For this reason, margins are not usually described after a procedure called a biopsy is performed for the purpose of removing only part of the tumour. The number of margins described in a pathology report depends on the types of tissues removed and the location of the tumour. The size of the margin (the amount of normal tissue between the tumour and the cut edge) depends on the type of tumour being removed and the location of the tumour.

Pathologists carefully examine the margins to look for tumour cells at the cut edge of the tissue. If tumour cells are seen at the cut edge of the tissue, the margin will be described as positive. If no tumour cells are seen at the cut edge of the tissue, a margin will be described as negative. Even if all of the margins are negative, some pathology reports will also provide a measurement of the closest tumour cells to the cut edge of the tissue.

A positive (or very close) margin is important because it means that tumour cells may have been left behind in your body when the tumour was surgically removed. For this reason, patients who have a positive margin may be offered another surgery to remove the rest of the tumour or radiation therapy to the area of the body with the positive margin. The decision to offer additional treatment and the type of treatment options offered will depend on a variety of factors including the type of tumour removed and the area of the body involved.

Margin

Were lymph nodes examined and did any contain cancer cells?

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small vessels called lymphatics. For this reason, lymph nodes are commonly removed and examined under a microscope to look for cancer cells. The movement of cancer cells from the tumour to another part of the body such as a lymph node is called a metastasis.

Cancer cells typically spread first to lymph nodes close to the tumour although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in the lymph node.

If any lymph nodes were removed from your body, they will be examined under the microscope by a pathologist and the results of this examination will be described in your report. Most reports will include the total number of lymph nodes examined, where in the body the lymph nodes were found, and the number (if any) that contain cancer cells. If cancer cells were seen in a lymph node, the size of the largest group of cancer cells (often described as “focus” or “deposit”) may also be included.

The examination of lymph nodes is important for two reasons. First, this information is used to determine the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment such as chemotherapy, radiation therapy, or immunotherapy is required.

What does it mean if a lymph node is described as positive?

Pathologists often use the term “positive” to describe a lymph node that contains cancer cells. For example, a lymph node that contains cancer cells may be called “positive for malignancy”.

What does it mean if a lymph node is described as negative?

Pathologists often use the term “negative” to describe a lymph node that does not contain any cancer cells. For example, a lymph node that does not contain cancer cells may be called “negative for malignancy”.

Lymph node

How do pathologists determine the pathologic stage (pTNM) for epithelioid sarcoma?

​The pathologic stage for epithelioid sarcoma is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer. 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. In general, a higher number means a more advanced disease and a worse prognosis.

Tumour stage (pT) for epithelioid sarcoma

The tumour stage for epithelioid sarcoma varies based on the body part involved. For example, a 5-centimetre 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.

Head and neck
  • T1 – The tumour is no greater than 2 centimetres in size.
  • T2 – The tumour is between 2 and 4 centimetres in size.
  • T3 – The tumour is greater than 4 centimetres 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.
Chest, back, or stomach and the arms or legs (trunk and extremities)
  • T1 – The tumour is no greater than 5 centimetres in size.
  • T2 – The tumour is between 5 and 10 centimetres in size.
  • T3 – The tumour is between 10 and 15 centimetres in size.
  • T4 – The tumour is greater than 15 centimetres in size.
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 it started.
  • T3 – The tumour has grown into at least one other organ.
  • T4 – Multiple tumours are found.
Retroperitoneum (the space at the very back of the abdominal cavity)
  • T1 – The tumour is no greater than 5 centimetres in size.
  • T2 – The tumour is between 5 and 10 centimetres in size.
  • T3 – The tumour is between 10 and 15 centimetres in size.
  • T4 – The tumour is greater than 15 centimetres in size.
Tissue around the eye (orbit)
  • T1 – The tumour is no greater than 2 centimetres in size.
  • T2 – The tumour is greater than 2 centimetres 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.
Nodal stage (pN) for epithelioid sarcoma

Epithelioid sarcoma is given a nodal stage of 0 or 1 based on the presence or absence of tumour cells in one or more lymph nodes. If no tumour 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 tumour cells are found in any lymph nodes, then the nodal stage is listed as N1.

Metastasis stage (pM) for epithelioid sarcoma

Epithelioid sarcoma is given a metastatic stage of 0 or 1 based on the presence of tumour cells at a distant site in the body (for example the lungs). The metastatic stage can only be assigned if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.

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