Synovial sarcoma

by Bibianna Purgina, MD FRCPC
August 16, 2024

Background:

Synovial sarcoma is a rare type of cancer that develops in the soft tissues of the body, such as muscles, fat, and connective tissues. Despite its name, synovial sarcoma does not usually start in the synovium (the tissue that lines joints) but can develop near joints or tendons. It is considered an aggressive cancer because it can grow quickly and spread to other parts of the body.

What are the symptoms of synovial sarcoma?

The symptoms of synovial sarcoma depend on the location and size of the tumour. Common symptoms include:

• A lump or swelling: Synovial sarcoma often presents as a painless lump or mass, which can grow over time.
• Pain or tenderness: Some patients may experience pain or discomfort, especially if the tumour is pressing on nearby nerves or muscles.
• Difficulty moving: If the tumour is near a joint, it may cause stiffness or difficulty moving the affected area.

What causes synovial sarcoma?

The exact cause of synovial sarcoma is not well understood, but it is thought to be related to specific genetic changes in the cells. Most cases occur sporadically, meaning they happen by chance and are not inherited.

What genetic changes are found in synovial sarcoma?

The most common genetic change found in synovial sarcoma is a specific rearrangement of two genes called SS18 and SSX. These genes fuse to form an abnormal gene called SS18-SSX, which drives the development of the tumour. This genetic change is not inherited but only found in the tumour cells.

How is the diagnosis of synovial sarcoma made?

The diagnosis of synovial sarcoma is usually made after a biopsy or surgery to remove the tumour. A pathologist examines the tissue under a microscope to look for features characteristic of synovial sarcoma. Additional tests, such as immunohistochemistry and molecular tests, may be performed to confirm the diagnosis.

Types of synovial sarcoma

Synovial sarcoma is divided into two main types:

• Biphasic type: This type of synovial sarcoma is made up of two kinds of cells: spindle cells and epithelial cells. The spindle cells are long and thin, while the epithelial cells are more rounded and can form nests, cords, or glands. The presence of both cell types is characteristic of the biphasic type.
• Monophasic type: This type is made up entirely of spindle cells, which are fairly uniform and relatively small. The spindle cells have sparse cytoplasm (the fluid inside the cell), ovoid (egg-shaped) hyperchromatic nuclei (dark-staining centers of the cells), and regular granular chromatin (the material in the nucleus) with inconspicuous nucleoli (small structures within the nucleus).

Poorly differentiated synovial sarcoma

In some cases, synovial sarcoma can undergo changes that make the tumour more aggressive. This is known as poorly differentiated synovial sarcoma. In this form, the tumour shows increased cellularity (more densely packed cells), greater nuclear atypia (abnormality in the shape and size of the cell nuclei), and high mitotic activity (rapid cell division). Poorly differentiated synovial sarcomas have more than 6 mitoses per mm² or more than 10 mitoses per 10 high-power fields under the microscope, indicating a high level of cell division.

Immunohistochemistry

Immunohistochemistry is a particular test that pathologists use to help confirm the diagnosis of synovial sarcoma. This test applies unique markers to the tissue sample to detect specific proteins in the tumour cells. Most synovial sarcomas are positive for TLE1, cytokeratins, and EMA. These markers help pathologists distinguish synovial sarcoma from other types of tumours that can look similar when examined under the microscope.

Molecular tests

Pathologists often use FISH (Fluorescence In Situ Hybridization) or NGS (Next-Generation Sequencing) to identify the genetic changes associated with synovial sarcoma. These tests detect the SS18-SSX gene fusion, which is a key feature of this tumour. FISH uses fluorescent probes to look for the gene fusion, while NGS sequences the DNA to identify the abnormal genes.

French Federation of Cancer Centres Sarcoma Grading System (FNCLCC)

The French Federation of Cancer Centres Sarcoma Grading system, or FNCLCC, is a system that pathologists use to grade sarcomas, including synovial sarcoma. The grade helps predict how the tumour will likely behave, including how fast it might grow and whether it might spread to other body parts.

The FNCLCC system assigns a score to the tumour based on three components:

• Mitotic activity: This refers to the number of cells that are actively dividing in the tumour. Pathologists count the number of mitotic figures (cells in the process of dividing) in an area measuring 10 high-powered fields under the microscope. The score for mitotic activity can range from 1 to 3, with a higher score indicating more frequent cell division and a potentially more aggressive tumour.
• Necrosis: Necrosis refers to areas of the tumour where the cells have died. The score for necrosis also ranges from 1 to 3, with a higher score indicating more extensive necrosis, which usually suggests a more aggressive tumour.
• Differentiation: Differentiation refers to how much the tumour cells look like normal cells. In the FNCLCC system, all synovial sarcomas are given a differentiation score of 3 because the tumour cells do not resemble normal cells.

The scores from these three components are added to give the tumour an overall grade, ranging from Grade 1 (low grade) to Grade 3 (high grade). A higher grade indicates a more aggressive tumour.

Tumour size

Tumour size is important because tumours less than 5 cm are less likely to spread to other body parts and are associated with a better prognosis. Tumour size is also used to determine the pathologic tumour stage (pT).

Tumour extension

Most synovial sarcomas tend to occur in the extremities (arms and legs) and are well-defined, but the tumour may grow into or around nearby organs and bones. This is called tumour extension. Your pathologist will examine samples of the surrounding organs and tissues under the microscope for tumour cells. Any surrounding organs or tissue that contains tumour cells will be described in your report.

Perineural invasion

Perineural invasion means that tumour cells were seen attached to a nerve. Nerves are found all over the body and are responsible for sending information (such as temperature, pressure, and pain) between the body and the brain. Perineural invasion is important because tumour cells 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.

Lymphovascular invasion

Lymphovascular invasion means tumour 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. Lymphovascular invasion is important because it increases the risk that the tumour will metastasize or spread to other body parts, such as lymph nodes or the lungs.

Margins

In pathology, a margin is the edge of tissue removed during tumour surgery. The margin status in a pathology report is important as it indicates whether the entire tumour was removed or if some was left behind. This information helps determine the need for further treatment.

Pathologists typically assess margins following a surgical procedure, like an excision or resection, that removes the entire tumour. Margins aren’t usually evaluated after a biopsy, which removes only part of the tumour. The number of margins reported and their size—how much normal tissue is between the tumour and the cut edge—vary based on the tissue type and tumour location.

Pathologists examine margins to check if tumour cells are at the tissue’s cut edge. A positive margin, where tumour cells are found, suggests that some cancer may remain in the body. In contrast, a negative margin, with no tumour cells at the edge, suggests the tumour was fully removed. Some reports also measure the distance between the nearest tumour cells and the margin, even if all margins are negative.

Treatment effect

If you have been diagnosed with synovial sarcoma on a biopsy, you may be offered chemotherapy and/or radiation therapy before the operation to remove the tumour. If you have received either of these treatments before your surgery, your pathologist will examine all the tissue sent to pathology to see how much of the tumour is still alive (viable).

Different systems are used to describe the treatment effects for synovial sarcoma. Most commonly, your pathologist will describe the percentage of dead tumour. Pathologists use the word necrosis to describe dead (non-viable) tumours. A tumour showing 90% or more therapy response (meaning 90% of the tumour is dead and 10% or less alive) is considered an excellent response to therapy and is associated with a better prognosis.

Lymph nodes

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread through small lymphatic vessels from a tumour to lymph nodes. 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 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. The examination of lymph nodes is important for two reasons. First, this information determines 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.

Some helpful definitions:

• Positive: Positive means that cancer cells were found in the lymph node being examined.
• Negative: Negative means that no cancer cells were found in the lymph node being examined.
• Deposit: The term deposit describes a group of cancer cells inside a lymph node. Some reports include the size of the largest deposit. A similar term is “focus”.
• Extranodal extension: Extranodal extension means that the tumour cells have broken through the capsule on the outside of the lymph node and have spread into the surrounding tissue.

Pathologic stage (pTNM)

​The pathologic stage for synovial sarcoma is based on the TNM staging system, an internationally recognized system 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 synovial sarcoma

The tumour stage for synovial sarcoma varies based on the body part involved. For example, a 5-centimetre tumour that starts in the head will be given a different stage than a tumour that begins 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 surrounding 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 synovial sarcoma

Synovial 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, the nodal stage is N1.