Synovial Sarcoma: Understanding Your Pathology Report

Synovial sarcoma is a rare type of soft tissue cancer. Despite its name, it does not usually start from the lining of joints (synovium). Instead, it arises from primitive connective tissue cells that exhibit features of both spindle-shaped cells and epithelial cells.

This article explains the pathology report for synovial sarcoma, including how it is diagnosed, what features pathologists look for, and how these findings relate to prognosis and treatment.

Where does synovial sarcoma develop?

Most synovial sarcomas develop in the deep soft tissues, especially:

• The lower and upper extremities (about 70% of cases) are often near joints.

• The trunk.

• Less commonly, the head and neck.

Although uncommon, synovial sarcoma can arise in many other locations, including internal organs such as the lung, kidney, gastrointestinal tract, heart, and even bone or nerve tissue. These unusual locations can make diagnosis more challenging.

What are the symptoms of synovial sarcoma?

Synovial sarcoma often presents as a slowly growing lump or swelling, which may or may not be painful. Because early growth can be slow and the tumour may appear well circumscribed on imaging, it is sometimes mistaken for a benign (non-cancerous) lesion.

Some tumours contain calcifications, which may be seen on imaging studies. More aggressive tumours can invade nearby structures, including bone, leading to pain or functional problems.

Who gets synovial sarcoma?

Synovial sarcoma can occur at any age and affects males and females equally. More than half of cases occur in adolescents and young adults, and about three-quarters of patients are diagnosed before the age of 50.

Among soft tissue sarcomas, synovial sarcoma is relatively common in children and young adults but becomes much less frequent with increasing age.

What causes synovial sarcoma?

There are no known lifestyle or environmental risk factors for synovial sarcoma. Very rarely, it has been linked to prior radiation therapy. Synovial sarcoma is driven by a specific genetic change found in the tumour cells. This change is not inherited and is not present in the rest of the body.

How does synovial sarcoma develop?

Nearly all synovial sarcomas contain a characteristic chromosomal translocation that joins two genes. This creates an SS18–SSX fusion gene (most often SS18–SSX1 or SS18–SSX2).

This fusion gene produces an abnormal protein that disrupts normal regulation of gene expression. In simple terms, it locks cells into an immature, cancer-forming state and prevents them from developing into normal tissue. Synovial sarcoma cells depend on this fusion protein to survive and grow.

Unlike many other cancers, synovial sarcoma usually has very few additional genetic mutations.

How is the diagnosis made?

The diagnosis is made by examining tumour tissue under the microscope and confirming the findings with immunohistochemistry and molecular testing.

Microscopic (pathologic) features

Under the microscope, synovial sarcoma is composed mainly of uniform spindle-shaped cells with minimal cytoplasm, giving the tumour a dark blue appearance on routine stains. These spindle cells grow in dense sheets or short fascicles and may show patterns such as herringbone or subtle nuclear palisading.

There are three main microscopic patterns:

• Monophasic synovial sarcoma: Made up almost entirely of spindle cells. This is the most common form.

• Biphasic synovial sarcoma: Contains both spindle cells and epithelial (gland-forming) cells. The epithelial component may form glands or solid nests and produce mucin.

• Poorly differentiated synovial sarcoma: Shows areas with more aggressive features, including higher cell density, more nuclear irregularity, increased mitotic activity, and sometimes necrosis. These areas may resemble other high-grade sarcomas or small round cell tumours.

Calcification, or bone formation, is seen in up to one-third of cases and can be extensive in some tumours.

Immunohistochemistry

Immunohistochemistry uses special stains to detect proteins in tumour cells.

Synovial sarcoma typically shows:

• EMA (epithelial membrane antigen) positivity, often more extensive than cytokeratin.

• Variable expression of cytokeratins, especially in biphasic tumours.

• TLE1, which shows strong nuclear staining in most cases, is a very helpful marker.

Other markers, such as BCL2 and CD99, are often positive but are not specific. S100 may be focally positive. Markers of smooth muscle differentiation are usually absent.

Because some markers overlap with other sarcomas, immunohistochemistry alone is not sufficient to make the diagnosis.

Molecular testing

Molecular testing is critical for confirming the diagnosis of synovial sarcoma.

Almost all cases show a t(X;18) chromosomal translocation, resulting in an SS18–SSX1, SS18–SSX2, or rarely SS18–SSX4 fusion gene. This fusion can be detected using tests such as FISH, RT-PCR, or next-generation sequencing.

Identifying this fusion confirms the diagnosis and helps distinguish synovial sarcoma from other spindle cell tumours.

French Federation of Cancer Centres Sarcoma Grading System (FNCLCC)

Pathologists use the French Federation of Cancer Centres Sarcoma Grading System (FNCLCC) to grade many sarcomas, including synovial sarcoma. The tumour grade helps predict how the cancer is likely to behave, such as how quickly it may grow and how likely it is to spread to other parts of the body.

The FNCLCC system evaluates three features seen under the microscope: mitotic activity, necrosis, and differentiation. These features are described below.

Mitotic activity

This refers to the number of tumour cells actively dividing. Pathologists count the number of dividing cells (called mitotic figures) in a defined area of the tumour. A higher number means the tumour is growing more quickly and is more aggressive.

Necrosis

Necrosis refers to areas of the tumour where cells have died. A higher amount of necrosis usually reflects rapid tumour growth that has outpaced its blood supply and is associated with more aggressive behaviour.

Differentiation

Differentiation describes how closely the tumour cells resemble normal tissue. In synovial sarcoma, the tumour cells do not resemble normal cells, so all synovial sarcomas receive the highest differentiation score in this system.

The scores from these three features are added together to assign an overall grade:

• Grade 1 (low grade).

• Grade 2 (intermediate grade).

• Grade 3 (high grade).

A higher grade indicates a more aggressive tumour and is associated with a worse prognosis.

Tumour size

Tumour size is an important feature in synovial sarcoma. Tumours that are smaller than 5 cm are less likely to spread to other parts of the body and are generally associated with a better prognosis.

Tumour size is also used to determine the pathologic tumour stage (pT), which plays a key role in staging and treatment planning.

Tumour extension

Although synovial sarcoma most often arises in the arms or legs and may appear well-defined, it can sometimes grow into or around nearby structures, including muscle, bone, or other tissues. This spread into surrounding structures is called tumour extension.

Your pathologist carefully examines tissue taken from around the tumour to see whether cancer cells have grown beyond the main mass. Any organs or tissues involved by tumour extension will be described in your pathology report.

Tumour extension is important because it is associated with a higher risk of local recurrence (the tumour coming back in the same area) and may affect tumour stage.

Perineural invasion

Perineural invasion (PNI) means that tumour cells are found growing along or around a nerve. Nerves are present throughout the body and transmit signals such as pain, temperature, and pressure.

Perineural invasion is important because tumour cells can use nerves as pathways to spread into surrounding tissues. When perineural invasion is present, the risk of local recurrence after treatment increases.

Lymphovascular invasion

Lymphovascular invasion (LVI) means that tumour cells are seen inside a blood vessel or a lymphatic vessel. Blood vessels carry blood, while lymphatic vessels carry lymph, a fluid that helps remove waste and transport immune cells.

Finding tumour cells in these vessels is important because it indicates a higher risk of metastasis, meaning the tumour may spread to other parts of the body, such as the lungs or lymph nodes.

Margins

A margin is the edge of tissue removed during surgery. Margin status tells doctors whether the tumour was removed entirely or whether some cancer cells may still be present.

Margins are usually evaluated after a surgical procedure that removes the entire tumour, such as an excision or resection. Margins are not typically assessed after a biopsy, which removes only part of the tumour.

Pathologists examine the margins to determine whether tumour cells are present at the cut edge:

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

• A positive margin indicates that tumour cells are present at the edge, suggesting that some tumour may remain in the body.

Some pathology reports also measure the distance between the closest tumour cells and the margin, even when margins are negative. Margin status is important because positive margins are associated with a higher risk of local recurrence and may influence decisions about additional treatment.

Treatment effect

If synovial sarcoma is first diagnosed on a biopsy, treatment such as chemotherapy and/or radiation therapy may be given before surgery to shrink the tumour. This is called neoadjuvant therapy.

If treatment is given before surgery, your pathologist will examine the removed tumour to see how much of it is still alive. Dead tumour cells are described as necrosis, while living tumour cells are described as viable.

Most commonly, the treatment response is reported as the percentage of tumour necrosis:

• A tumour showing 90% or more necrosis (meaning 10% or less of the tumour is still alive) is considered an excellent response to treatment and is associated with a better prognosis.

• Tumours with less necrosis are considered to have a poorer response to therapy.

Treatment response helps doctors assess how well the tumour responded to therapy and may influence further treatment and follow-up planning.

Pathologic stage (pTNM)

The pathologic stage describes the extent of synovial sarcoma’s spread based on examination of tissue removed during surgery. Staging is determined using the TNM staging system, an internationally recognized system developed by the American Joint Committee on Cancer.

This system combines information about:

• T (tumour) – the size of the tumour and how far it has grown locally,

• N (nodes) – whether cancer cells have spread to nearby lymph nodes, and

• M (metastasis) – whether cancer has spread to distant organs.

Your pathologist assigns a number to each of these categories. In general, higher numbers mean more advanced disease and a worse prognosis. The complete stage is reported as pTNM.

Tumour stage (pT) for synovial sarcoma

The tumour stage depends on where in the body the tumour started. This is because the same-sized tumour can behave differently depending on its location. For example, a 5-centimetre tumour in the head is staged differently from a 5-centimetre tumour deep in the abdomen.

In most locations, tumour stage is based on tumour size and whether the tumour has grown into nearby structures.

Head and neck

• T1 – The tumour is 2 cm or smaller.

• T2 – The tumour is larger than 2 cm but no larger than 4 cm.

• T3 – The tumour is larger than 4 cm.

• T4 – The tumour has grown into nearby vital structures, such as the bones of the face or skull, the eye, major blood vessels in the neck, or the brain.

Chest, back, abdomen wall, arms, or legs (trunk and extremities)

• T1 – The tumour is 5 cm or smaller.

• T2 – The tumour is larger than 5 cm but no larger than 10 cm.

• T3 – The tumour is larger than 10 cm but no larger than 15 cm.

• T4 – The tumour is larger than 15 cm.

Abdomen and organs inside the chest (thoracic visceral organs)

• T1 – The tumour is confined to one organ.

• T2 – The tumour has grown into the connective tissue surrounding the organ.

• T3 – The tumour has grown into at least one nearby organ.

• T4 – Multiple tumours are present.

Retroperitoneum

(The space at the very back of the abdominal cavity)

• T1 – The tumour is 5 cm or smaller.

• T2 – The tumour is larger than 5 cm but no larger than 10 cm.

• T3 – The tumour is larger than 10 cm but no larger than 15 cm.

• T4 – The tumour is larger than 15 cm.

Tissue around the eye (orbit)

• T1 – The tumour is 2 cm or smaller.

• T2 – The tumour is larger than 2 cm but has not grown into the surrounding bones.

• T3 – The tumour has grown into the bones around the eye or skull.

• T4 – The tumour has grown into the eye itself or nearby structures such as the eyelids, sinuses, or brain.

Nodal stage (pN) for synovial sarcoma

The nodal stage describes whether cancer cells have spread to lymph nodes, which are small immune organs that help filter lymph fluid.

• pN0 – No cancer cells are found in any lymph nodes examined.

• pN1 – Cancer cells are found in one or more lymph nodes.

• pNX – No lymph nodes were sent for examination, so the nodal stage cannot be determined.

Lymph node involvement is uncommon in synovial sarcoma, but when present, it is associated with more advanced disease and may influence treatment decisions.

What is the prognosis for a person with synovial sarcoma?

The prognosis for a person diagnosed with synovial sarcoma varies widely. Important factors include:

• Tumour size (smaller tumours do better).

• Stage at diagnosis.

• Tumour grade.

• Location (extremity tumours have a better outcome than trunk or head and neck tumours).

Children and adolescents generally have better outcomes than adults. Some patients experience late recurrences, even more than 10 years after diagnosis, so long-term follow-up is essential.

Questions to ask your doctor

• Was molecular testing performed, and what fusion was found?
• What is the FNCLCC grade?
• Has the tumour spread to the lungs or lymph nodes?
• What treatments are recommended for my stage of disease?
• How long will follow-up be needed after treatment?