What causes synovial sarcoma

Overview

Synovial sarcoma is a rare and aggressive form of soft tissue sarcoma. Despite its name, it does not originate from the synovial cells that line joints. Instead, it is believed to arise from primitive mesenchymal stem cells that have the potential to differentiate into various cell types, including those that might resemble synovial cells. This tumor can occur in various parts of the body, most commonly in the extremities, particularly around large joints like the knee, elbow, and ankle. However, it can also develop in the trunk, head, neck, and internal organs.

The development of synovial sarcoma, like other cancers, is a complex process involving genetic alterations. While the exact triggers are not fully understood, research has identified a specific genetic abnormality that is highly characteristic of this tumor type. This genetic hallmark plays a crucial role in the formation and progression of synovial sarcoma and is a key factor in its diagnosis.

Details

What is Synovial Sarcoma?

Synovial sarcoma is classified as a mesenchymal tumor, meaning it originates from connective tissues such as muscle, fat, nerve, or bone. It is one of over 50 different types of soft tissue sarcomas. These tumors are characterized by their ability to grow and invade surrounding tissues, and they have the potential to metastasize, or spread, to other parts of the body, most commonly to the lungs.

The term 'synovial' was historically used because the tumor was often found near joints and its microscopic appearance could sometimes mimic tissues found in the synovium. However, modern genetic and molecular studies have shown that it does not arise from the synovial membrane itself. It is now understood to be a malignancy of primitive cells with the capacity for differentiation.

What Causes Synovial Sarcoma?

The precise cause of synovial sarcoma remains unknown, but scientific research has pointed towards specific genetic mutations as the primary drivers. The most significant finding is a recurrent chromosomal translocation, denoted as t(X;18)(p11.2;q11.2). This translocation involves the swapping of genetic material between the X chromosome and chromosome 18.

This specific translocation leads to the fusion of the SS18 gene (located on chromosome 18) with one of the SSX genes (located on the X chromosome). The most common fusion partners are SSX1, SSX2, and less frequently, SSX4. This fusion gene, such as SS18-SSX1 or SS18-SSX2, produces an abnormal protein that disrupts normal cellular function. This disruption is believed to promote uncontrolled cell growth and contribute to the development of sarcoma.

Genetic Factors and Translocations

The SS18-SSX fusion gene is considered a hallmark of synovial sarcoma and is present in approximately 80-90% of cases. The presence of this specific translocation is invaluable for diagnosis, helping to distinguish synovial sarcoma from other soft tissue tumors. While the translocation itself is the key genetic event, the exact environmental or cellular factors that initiate this translocation in the first place are still under investigation. It is not considered a hereditary condition, meaning it is not typically passed down through families.

Risk Factors

Unlike some other cancers, there are no well-established environmental risk factors definitively linked to the development of synovial sarcoma. Age is a factor, as it most commonly affects young adults between 20 and 40 years old. There is no known association with lifestyle choices, diet, or exposure to common carcinogens. Some research has explored potential links to previous radiation exposure or certain genetic syndromes, but these are not considered major causes.

Symptoms of Synovial Sarcoma

The symptoms of synovial sarcoma often depend on the location and size of the tumor. Common signs can include:

• A palpable lump or swelling, which may or may not be painful.
• Pain in the affected area, which can be constant or intermittent, and may worsen at night.
• Limited range of motion in a nearby joint if the tumor is pressing on it.
• In some cases, especially in the early stages, the tumor may be asymptomatic and only discovered incidentally on imaging performed for other reasons.

Diagnosis and Treatment

Diagnosis typically involves imaging tests (such as MRI, CT, or PET scans) to assess the size and location of the tumor and to check for spread. A biopsy is essential to confirm the diagnosis and determine the specific type of sarcoma. Genetic testing of the tumor cells can often detect the characteristic SS18-SSX fusion gene, aiding in definitive diagnosis. Treatment usually involves a multidisciplinary approach, including surgery to remove the tumor, often followed by radiation therapy and sometimes chemotherapy, depending on the stage and characteristics of the sarcoma.