Synovial Sarcoma Metastatic

Metastatic synovial sarcoma occurs when this rare, aggressive cancer spreads beyond its original location to other parts of the body, most commonly the lungs and lymph nodes, significantly impacting survival and treatment options.

Table of contents

• What Is Synovial Sarcoma
• Understanding Metastatic Disease
• Symptoms and Clinical Presentation
• Causes and Genetic Changes
• Diagnosis and Testing
• Treatment Options
• Prognosis and Survival

What Is Synovial Sarcoma

Synovial sarcoma is a rare type of cancer that affects soft tissues, such as muscles, ligaments, and tendons^[2]. Despite its name, this cancer does not actually come from the tissue that lines joints. The term “synovial” is misleading because the tumor can develop anywhere in the body, not just near joints^[1].

This cancer is particularly aggressive and has a high potential for spreading to other parts of the body^[1]. In the United States, approximately 800 to 1,000 new cases are diagnosed each year, making it account for up to 10% of all soft tissue sarcomas^[1]. Synovial sarcoma most commonly affects adolescents and adults younger than 30 years old, and it is considered the most common sarcoma in the adolescent age group^[1].

The cancer typically appears in the extremities near large joints like the knees, ankles, elbows, hips, and shoulders. However, it can also occur in the abdomen, arms, feet, legs, and lungs, and very rarely in the chest, head, or neck^[2].

synovial cell sarcoma, malignant synovioma

Understanding Metastatic Disease

Metastatic disease occurs when cancer cells spread from the original tumor to other parts of the body. For synovial sarcoma, this spreading is common and represents a significant challenge in treatment and survival^[4].

The lungs are the most frequent site where synovial sarcoma spreads. About 50% of patients with high-grade synovial sarcoma eventually develop lung metastases, and in approximately 70% of these patients, the lungs remain the only organ affected by metastatic disease^[1]. Lymph nodes are another common site for metastasis^[4].

Advanced synovial sarcoma can present in several ways. The tumor may be too large to be fully removed by surgery, the cancer may have already spread to other areas of the body when first diagnosed, or the cancer may return after treatment^[6]. About 10% of patients present with synchronous metastatic disease, meaning the cancer has already spread at the time of initial diagnosis^[10].

Symptoms and Clinical Presentation

Synovial sarcoma grows very slowly, which can delay diagnosis. Tumors may grow undetected for up to two years, and during this time, patients may not experience any symptoms at all^[2].

When symptoms do appear, they typically include a lump that you can see and feel, which might be painless. Other symptoms may include numbness, pain, and swelling^[2]. If the tumor grows near nerves, it can cause pain or numbness as it presses against them^[7].

The symptoms of synovial sarcoma can resemble those of other, less serious conditions such as arthritis (joint inflammation) or bursitis (inflammation of fluid-filled sacs near joints). This similarity can lead to misdiagnosis and delays in proper treatment^[2]. On average, it can take up to two years from the start of symptoms to diagnosis, which can increase the likelihood that the cancer will be advanced when finally identified^[14].

Causes and Genetic Changes

The exact cause of synovial sarcoma is not fully understood, but researchers know it involves changes in chromosomes. Chromosomes are structures in cells that contain genes, which carry instructions for how cells function^[2].

In synovial sarcoma, a specific genetic change occurs where parts of chromosomes break and rejoin incorrectly. A gene called SS18 (formerly called SYT) on chromosome 18 joins with genes called SSX (usually SSX1 or SSX2) on chromosome X. This abnormal joining is written as t(X;18)(p11.2;q11.2), and it occurs in more than 90% of patients with synovial sarcoma^[1]. This genetic change is so characteristic that it is considered a defining feature of the disease^[1].

The abnormal fusion creates proteins called SS18:SSX fusion proteins, which cause cells to not work as they should, leading to cancer development^[2]. There are no known environmental or inherited risk factors associated with synovial sarcoma^[1]. Radiation-induced synovial sarcoma is extremely rare but has been reported^[1].

Diagnosis and Testing

Diagnosing synovial sarcoma can be complex because the cancer may resemble other illnesses or injuries. A healthcare provider will start with a physical examination and ask about symptoms and medical history. If synovial sarcoma is suspected, referral to an oncologist (a doctor who specializes in cancer) is necessary^[2].

Several imaging tests are used to determine the size and location of the tumor and whether it has spread. These tests include X-rays, magnetic resonance imaging (MRI) scans, ultrasound, and computed tomography (CT) scans^[2][7].

A biopsy is essential for confirming the diagnosis. During this procedure, a small sample of tissue is removed from the tumor using a needle inserted through the skin, or sometimes through surgery. The tissue sample is examined in a laboratory to determine if it is cancer^[2][7].

Special laboratory tests look for the characteristic chromosome changes (the SS18:SSX fusion) to confirm that the tumor is synovial sarcoma. Doctors use this information, along with details about the tumor’s size, location, and whether it has spread, to create a treatment plan^[7][12].

Treatment Options

Treatment for metastatic synovial sarcoma is challenging and typically involves multiple approaches. The main treatment options include surgery, radiation therapy, and chemotherapy, though their use depends on the extent of disease spread^[1].

Surgery

Surgery remains the cornerstone of treatment for synovial sarcoma when possible. The goal is to remove the entire tumor along with a margin of healthy tissue around it to ensure no cancer cells remain. Complete surgical removal with clear margins provides the best chance for survival^[1][7]. However, when the cancer has spread to other parts of the body, complete removal may not be possible^[7].

Radiation Therapy

Radiation therapy uses powerful energy beams to kill cancer cells. It can be given before surgery to shrink the tumor and make successful removal more likely, or after surgery to reduce the chances of the cancer returning^[12][21].

Chemotherapy

Chemotherapy uses drugs to kill cancer cells throughout the body. Compared to other soft tissue sarcomas, synovial sarcoma is relatively responsive to chemotherapy^[10]. The role of chemotherapy in adults remains somewhat controversial, though it is regularly used in children^[1].

For patients with metastatic disease, doxorubicin-based chemotherapy is typically recommended as first-line treatment. In fit patients, combination treatment with doxorubicin and ifosfamide is a preferred option, while sequential treatment may be considered for others^[10]. Chemotherapy is particularly important when the tumor cannot be completely removed by surgery or when it has already spread^[7].

For patients who have received first-line chemotherapy, second-line options include pazopanib and trabectedin, which have shown activity against synovial sarcoma^[10]. Other regimens being used include combinations of ifosfamide with etoposide, docetaxel with gemcitabine, and single agents such as dacarbazine and eribulin^[9].

Emerging Therapies

Many new approaches are currently under investigation for metastatic synovial sarcoma, including targeted therapies, drugs that modify how genes are expressed, compounds that interfere with DNA repair, and immunotherapy treatments^[10].

Prognosis and Survival

The outlook for patients with metastatic synovial sarcoma is generally poor. Patients with metastasized soft tissue sarcomas typically have a median survival of about 12 months, though recent studies report improvements with treatment, showing median overall survival of 16 to 17 months^[18][4].

Several factors influence prognosis in synovial sarcoma. Stage 4 disease (metastatic synovial sarcoma) has a particularly poor prognosis^[22]. The size of the tumor matters significantly—tumors that are 5 centimeters or smaller have a better outlook than larger ones^[22].

Other important factors affecting prognosis include how deeply the tumor is located in the body, with surface tumors having better outcomes than deep tumors; where the cancer started, with tumors in the arms, legs, or surface of the trunk having better outcomes; and the tumor’s grade (a measure of how quickly cancer cells are growing), with low-grade tumors having better outcomes^[22].

The ability to completely remove the tumor through surgery is crucial. When all of the tumor can be removed and there is no sign of cancer elsewhere in the body, there is a better chance of survival^[7]. Age also plays a role, with people under 50 years old tending to have better outcomes than those over 50^[22].

Because synovial sarcoma is rare, survival rates may not be very accurate, and estimates generally show that anywhere from 36% to 76% of people with synovial sarcoma will be alive five years after diagnosis^[7]. These figures do not account for newer treatments currently being developed.