Synovial sarcoma is a rare, soft tissue cancer that usually occurs in young to middle-aged people, mostly in limbs, although it can arise anywhere in the body.¹ There is a specific genetic defect responsible for this cancer in most cases. Treatment is usually surgery with radiotherapy and sometimes chemotherapy.

Overview

Synovial sarcoma, like all sarcomas, means a cancer arising from soft tissue. Despite its name, this cancer does not arise from the synovium. In fact, the cell of its origin is unclear. Some reports claim that this cancer originates from a primitive cell type called a multipotent stem cell.¹ Treatment is mainly surgery with variable outcomes that largely depend on the stage of the cancer. Synovial sarcoma can often spread to bones and lungs.

What causes synovial sarcoma?

No definitive cause has been identified for this cancer.² A weak association is reported with previous radiation to the area.¹

What is known is that there is a genetic translocation in about 90% of the cases.² This means a swap of genetic material between two chromosomes, which are the units that carry all our genes. This translocation is known as SS18-SSX1.

How common is synovial sarcoma?

There are about 79 cases diagnosed every year in England.²

Of all soft tissue sarcomas, synovial sarcomas make up about 2%.²

Does synovial sarcoma arise from synovium?

No. Despite the name, it does not arise from the synovium.

What are the symptoms of synovial sarcoma?

The symptoms depend on the site of origin of the cancer. Wherever it arises from, it presents as a lump which may be painless or painful.^5,7

Common sites in order of most frequency to least include

1. Extremities like arms and legs¹, especially around joints⁵
2. Head and neck
3. Within the chest cavity
4. Within the abdominal cavity

What are the physical findings in synovial sarcoma?

There may be a visible lump, especially on the arms and legs and near the joints. In other cases the lump can be deeper within the body.

What are the types of synovial sarcoma?

There are mainly two types of synovial sarcoma, as seen under the microscope.¹

1. Monophasic-only one type of cell arrangement is seen
2. Biphasic- two types of cell arrangement are seen, including sheets of spindle-shaped cells and gland-like arrangement of cells 

Rarely there can be other subtypes like poorly differentiated, myxoid, calcifying/ossifying etc¹

How is synovial sarcoma diagnosed?

Imaging

Radiology is often helpful in suspecting this diagnosis. A soft tissue shadow can be seen, sometimes with spotty calcifications in an x-ray of the lesion. CT scans are used to assess whether there is erosion of the underlying bone, which is not uncommon.⁶ Also CT scans are needed to check for spread of this disease into other parts of the body such as the chest. However imaging alone with scans is not adequate for diagnosis of synovial sarcoma.

Biopsy

The diagnosis of synovial sarcoma requires sampling of the cancer. This is called a biopsy, which is a small sample taken from the growth or lump.

The sample is then processed in the laboratory and viewed under the microscope.

Most of the time, this sample will require additional tests called immunohistochemistry. Immunohistochemistry means a way of getting a special stain to bind to cancer cells so that they light up under the microscope and can be identified as those belonging to a particular cancer.

Genetic testing

This is used to identify the genetic translocation that is seen in 90% of cases of synovial sarcoma.

What is the confirmatory genetic test?

Identifying the genetic translocation or genetic material mix-up will help to confirm synovial sarcoma together with the appropriate appearance in biopsy.

Since the translocation is present in 90% of this cancer, there's a high chance of confirming it with this test.

There are different types of tests that are used to diagnose this translocation. They are FISH(Fluorescence-in situ- hybridisation), RT-PCR or NGS.

What are the grades of synovial sarcoma?

Cancer grading is a way of classifying the severity of cancer based on its microscopic appearance, usually. This is not about its spread to other organs.

The grading for synovial sarcoma is based on a famous grading system called FNCLCC.⁹

The factors they consider are:

• how much of the tumour is dead (necrosis) (This is because fast-growing tumours outstrip their blood supply and the cells die as a result)
• how much proliferating(multiplying) activity there is (mitotic figures)
• how identifiable the tumour cells are compared to normal cells or its tissue of origin (differentiation)

What are the stages of synovial sarcoma?

Every cancer needs staging to understand to what level cancer has spread and to guide treatment. Staging is usually based on the standard TNM staging or staging with a number, which is used for most soft tissue sarcomas.⁸

What is the treatment for synovial sarcoma?

• Surgery: Surgically removing the cancer is the mainstay of treatment and can be life-saving. It is important that the surgical procedure achieves a good margin, free of tumour,⁶ since otherwise there can be recurrences. Surgery can be sometimes complicated by the fact that the cancer lies close to important blood vessels and nerves especially to limb girdles^6,7
• Radiotherapy: There is a definite place for radiotherapy when used together with surgery since there is evidence that it reduces recurrences³ and improves overall survival¹
• Chemotherapy: This is sometimes used in high-risk cases although there is some controversy surrounding this^1,3

Can synovial sarcoma spread to other parts of the body, or in other words metastasize, and if so where?

Yes. Synovial sarcoma is known to spread easily to the lungs, and can also spread to bones, lymph nodes and even the brain.¹

What is the prognosis or in other words, outcome for synovial sarcoma?

The outcome for synovial sarcoma is based on factors like the tumour location, size and even grade.⁶

The outcome of Synovial sarcoma in distal extremities is reported to be better than in proximal extremities or trunk for example.⁶

Synovial sarcoma also tends to be a cancer which metastasizes quite easily and the outcome also depends on that.

Generally, the survival rates are said to be about 50 to 60 % at 5 years.

What factors are associated with a poor outcome for synovial sarcoma?

There are a few factors which if they are present are associated with a worse outcome.¹

These include:

• Increased size
• Those assigned as male at birth (AMAB)
• Presence of the genetic mutation of SSX18: SSX1
• Monophasic type
• Size more than 5 cm
• Older age at diagnosis

What are the new and research level treatments for synovial sarcoma?

Some newer treatments are available for synovial sarcoma. But they need more research evidence to establish their effectiveness

• Treatment with a medication called Pazopanib, which is a tyrosine kinase inhibitor has shown some promise in recent trials¹
• Some early studies showed a benefit in a newer form of treatment called immunotherapy. In this case T cell based immunotherapy has shown some benefit clinically for the patient¹

What other cancers can be mistaken as synovial sarcoma under the microscope?

Cancers that show high-grade, spindle-shaped cells under the microscope can be confused for synovial sarcoma. Some of the salient features of synovial sarcoma are said to be the ‘blue’ appearance of this cancer and also irregularly, dilated, small blood vessels within it.

Immunohistochemical stains will often resolve this issue.

Can I prevent synovial sarcoma?

Since the causes are not established clearly, no definitive preventive measures can be identified. Noticing any growths or lumps in your body and seeking medical advice early is the best way to achieve a good outcome for any cancer.

Summary

Synovial sarcoma is a soft tissue cancer that arises in middle-aged people, usually in limbs but with the possibility of occurring in many organs. A genetic material swap within the chromosomes is responsible for most of these cancers. The cancer needs to be surgically removed with subsequent radiotherapy and sometimes chemotherapy. The outcome depends on the location of the cancer, grade, stage of cancer and related factors.