What Is Synovial Sarcoma? Causes, Symptoms and Treatment

Synovial sarcoma is a rare type of soft tissue cancer (accounting for 5-10% of soft tissue cancers). Although it can occur anywhere in the body, it most often arises in cells around joints and tendons near the knee. In general, 1 in 3 patients diagnosed with synovial sarcoma is under 30, and it is more common in men.

When examined under a microscope, a synovial sarcoma tumor is seen in the following 4 main histopathological types:

• biphasic type
• monophasic spindle cell type
• monophasic epithelial type
• poorly differentiated type

What Are the Risk Factors and Causes of Synovial Sarcoma?

No definitive risk factor for synovial sarcoma has yet been identified. It has been suggested that the disease may be associated with a chromosomal translocation involving chromosome 18 and the X chromosome (a broken part of one chromosome attaching to another). It is not yet known whether this occurs randomly or follows a specific chain of cellular/genetic events. Ultimately, the mutant gene resulting from this chromosomal translocation is thought to cause synovial sarcoma to develop.

Metal hip replacement implants and radiation therapy for Hodking lymphoma have also been associated with synovial sarcoma.

What Are the Symptoms of Synovial Sarcoma?

The symptoms caused by synovial sarcoma differ according to the tumor's location.

It is a progressively growing tumor. It initially grows at a moderate rate, and there may generally be no symptoms until it reaches a certain size. It may then suddenly continue growing rapidly. The first symptoms may become apparent as the tumor grows.

• A lump or swelling
• The tumor may cause pain and numbness, particularly if it is close to nerves.
• In the head and neck region, it may cause difficulty swallowing or breathing, or a change in voice.

Before diagnosis, all or some of these symptoms may be present, or there may be no symptoms at all.

How Is Synovial Sarcoma Staged?

Grading

• Low grade: means that cancer cells grow slowly, look quite similar to normal cells, are less aggressive and are less likely to spread.
• Intermediate grade: means that cancer cells grow somewhat faster and look more abnormal.
• High grade: means that cancer cells grow quickly, look very abnormal, are more aggressive and are more likely to spread.

Staging

• Stage 1: means that the cancer is low-grade, small (less than 5 cm) and has not spread to other parts of the body.
• Stage 2: means that the cancer can be of any grade and is generally larger than at the first stage, but has not spread to other parts of the body.
• Stage 3: means a high-grade cancer that has not spread to other parts of the body
• Stage 4: means cancer of any grade or size that has spread anywhere in the body.

How Is Synovial Sarcoma Diagnosed?

As with other soft tissue cancers, diagnosis of synovial sarcoma usually begins when a patient notices a lump or swelling.

Patients consulting a physician with these complaints undergo a series of tests:

• Physical examination
• Imaging (ultrasound, X-ray, Computed Tomography (CT), Endoscopic Ultrasound Scan (EUS), Positron Emission Tomography (PET), Magnetic Resonance Imaging (MRI))
• Biopsy (taking and examining a tissue sample from the mass)
• Genetic testing and analysis (to determine whether a chromosomal translocation is present)

Diagnosis is made from the results of these tests.

How Is Synovial Sarcoma Treated?

Synovial sarcoma is a type of soft tissue sarcoma. Soft tissue sarcomas are a heterogeneous group of rare tumors arising from mesenchymal cells in all body regions. A consensus is emerging that, particularly in advanced (stage 4) disease, treatment selection should be histology-driven.

The basic treatment principles for soft tissue sarcomas are as follows:

• Surgical removal of metastatic tumors may provide long-term recurrence-free survival and possibly a cure in selected patients, most of whom have isolated lung metastases.
• For most patients with metastatic soft tissue sarcoma, however, chemotherapy is used to reduce tumor volume, alleviate symptoms, improve quality of life and prolong survival, with palliative intent. Objective response rate (assessed by a reduction in the size of measurable lesions) is a poor surrogate endpoint for benefit in metastatic soft tissue sarcoma, particularly for molecularly targeted therapies and drugs such as trabectedin.
• The natural course of unresectable metastatic sarcoma varies and is influenced by treatment as well as disease biology. For some patients with asymptomatic, low-grade, inoperable disease (e.g., low-grade intra-abdominal leiomyosarcoma [LMS]), observation without active chemotherapy may be reasonable. Conversely, for patients with a high-grade, chemotherapy-sensitive tumor such as synovial sarcoma or liposarcoma, early use of combination chemotherapy may be preferred.
• Patients with advanced, surgically unresectable soft tissue sarcoma are suitable candidates for clinical trials to identify more active treatment approaches. If trial participation is not possible, conventional systemic therapy is an appropriate option for selected patients.

How Should First-Line Treatment Be Selected?

For patients with sarcoma, "anthracyclines" are the first chemotherapy option that comes to mind.

• Sarcoma subtypes known to be sensitive to anthracyclines include leiomyosarcoma, myxoid / round cell liposarcoma, epithelioid sarcoma, dedifferentiated and pleomorphic liposarcoma, synovial sarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma and malignant peripheral nerve sheath tumor. For these sarcoma types, we recommend doxorubicin with or without ifosfamide rather than other treatments. In symptomatic patients needing the fastest possible tumor response, combination therapy with doxorubicin plus ifosfamide may be preferred over doxorubicin alone.
  • A gemcitabine-based combination may be recommended as an alternative in cases of heart failure or inability to receive anthracyclines.
  • Paclitaxel is a reasonable alternative to anthracyclines for initial treatment of patients with angiosarcoma.
• For patients with poorer performance status or extensive comorbidities who are still suitable for chemotherapy, options include liposomal doxorubicin, gemcitabine alone or a gemcitabine-based combination.
• Treatment of anthracycline-resistant sarcoma subtypes: Some sarcoma subtypes are not sensitive to anthracyclines, the standard treatment.

The Importance of Genetic Testing in Advanced Synovial Sarcoma

Genetic testing is now necessary in many advanced solid (organ) cancers to offer new treatment options. Genetic testing in cancer now brings to mind next-generation sequencing (NGS = Next Generation Sequencing) (for example, Genekor's PRIME Extended test).

Next-generation sequencing can test eligibility for molecularly targeted drugs approved by the US Food and Drug Administration (FDA). These agents include targeted drugs that can be used according to the tumor biomarker regardless of organ, such as larotrectinib or entrectinib. These drugs were developed against neurotrophic tyrosine receptor kinase (NTRK) genetic alterations. The immunotherapy pembrolizumab (Keytruda) is also approved regardless of organ for patients with high tumor mutational burden (TMB-high) and microsatellite instability (MSI-High) by the FDA.

Another treatment being investigated for synovial sarcoma is a type of immunotherapy called adoptive cell therapy. Metastatic (stage 4) synovial sarcoma cells contain an antigen called NY-ESO-1 / LAGE1a in 70% to 80% of cases. An antigen is a toxin or other foreign substance that can trigger the immune system, particularly antibody production. Modified to target this antigen using a T-cell receptor, T cells produced a strong antitumor response in patients with synovial cancer. A complete response in 1 patient was reported in a noteworthy study published in Cancer Discovery on June 11, 2018.

What Are the Survival Statistics for Synovial Sarcoma?

Facing a rare cancer can make the situation difficult to assess. Survival rates for synovial sarcoma are affected by recurrence or spread. In general, overall 5-year survival can be said to range between 36% and 76%. These rates naturally vary from patient to patient.

In summary, factors affecting prognosis (the course of the disease) include:

• small tumor size (less than 5 cm)
• a tumor that is easy to remove surgically
• a localized tumor (not spread)
• the patient's age

Does Synovial Sarcoma Recur?

Synovial sarcoma may reappear in the same area after treatment, which is called local recurrence.

It is important to treat the cancer as early as possible if it returns. Treatment may include surgery and/or radiotherapy. This is assessed individually for each patient.