What is Synovial Sarcoma?

Synovial sarcoma is a rare and aggressive cancer originating primarily in deeper soft tissues such as muscles, tendons, ligaments, and fibrous connective tissue, typically close to joints. Despite its name, synovial sarcoma does not originate from synovial tissue, which is the specialized lining found inside joints. Instead, it received its name because cancer cells closely resemble synovial cells under a microscope.

Synovial sarcoma is classified as an orphan disease, indicating that it is exceptionally rare, historically receiving limited research funding and medical attention. Due to its rarity, it has posed significant challenges for accurate diagnosis, treatment advancement, and patient support. The Synovial Sarcoma Foundation aims to bridge these gaps by promoting research, awareness, and improved medical outcomes.

Where Does Synovial Sarcoma Occur? 

Synovial sarcoma can occur virtually anywhere in the body but most often develops in soft tissues near large joints. According to a comprehensive patient survey conducted by the Synovial Sarcoma Foundation involving over 200 respondents:

  • Legs (32%) – especially near the knee and thigh.
  • Chest (17%) – often within the thoracic cavity, lungs, or chest wall.

Other frequent locations include:

  • Arms: especially near the elbows, wrists, or forearms.
  • Ankles and feet: often appearing as a lump or swelling.
  • Hips and pelvis: near major joints or muscles.
  • Shoulders: typically around or just below the joint.

Though less common, synovial sarcoma can also develop internally in areas such as the abdomen, heart, or head and neck regions, making diagnosis more challenging.

Who Does Synovial Sarcoma Affect?

Synovial sarcoma is rare but most frequently diagnosed in younger individuals, typically between the ages of 15 and 40. Approximately one-third of cases are diagnosed in individuals under age 30. It occurs slightly more often in males than females, though individuals of all genders and ethnicities can be affected.

This type of sarcoma is exceptionally uncommon, accounting for approximately 5% to 10% of all soft tissue sarcomas. Soft tissue sarcomas themselves make up less than 1% of all cancers, meaning synovial sarcoma is incredibly rare, occurring in just 1 to 2 individuals per million annually.

What Causes Synovial Sarcoma?

The exact cause of synovial sarcoma remains unknown, but researchers have identified that it is driven by a genetic mutation. This mutation occurs when parts of two genes—SS18 (formerly called SYT) and SSX1, SSX2, or less commonly, SSX4—fuse together. This fusion produces an abnormal protein that disrupts normal cellular function, leading to uncontrolled cell growth and tumor formation.

While we know the genetic mechanism behind synovial sarcoma, the factors that cause this mutation to occur in the first place remain unclear. Scientists have studied several possibilities, but no definitive environmental, lifestyle, or inherited genetic causes have been identified:

  • Not Typically Inherited: Synovial sarcoma is not considered hereditary, meaning it does not typically run in families. The SS18-SSX fusion mutation arises spontaneously in affected cells rather than being passed down genetically (Dana-Farber Cancer Institute).
  • Environmental Factors: There is no conclusive evidence linking synovial sarcoma to environmental exposures, such as radiation, toxins, or chemicals. However, researchers continue to explore whether certain exposures could increase the risk of developing this mutation.
  • Random Cellular Events: Like many cancers, synovial sarcoma may develop due to random errors during cell division. Over time, normal cellular processes can occasionally go awry, resulting in mutations like the SS18-SSX fusion.
  • Potential Influences of Age and Development: Synovial sarcoma is most commonly diagnosed in adolescents and young adults, suggesting a possible connection to rapid cellular growth or developmental processes during these life stages. However, this remains an area of active research.
  • No Established Risk Factors: Unlike some cancers, synovial sarcoma does not have well-established risk factors, such as smoking or a family history of related conditions. This makes predicting or preventing the disease challenging.

Are There Different Types of Synovial Sarcoma?

Synovial sarcoma can be divided into three main types based on cellular appearance under the microscope. Identifying the specific type of synovial sarcoma helps doctors predict the tumor’s behavior and guide appropriate treatment decisions.

  • Monophasic Synovial Sarcoma: The most common type, comprising about 60% to 70% of cases. These tumors primarily contain spindle-shaped cells, closely resembling fibrous or connective tissue.

  • Biphasic Synovial Sarcoma: Making up around 20% to 30% of cases, biphasic tumors include two distinct cell types: spindle-shaped cells and epithelial-like cells, which have a rounded, glandular appearance.

  • Poorly Differentiated Synovial Sarcoma: The rarest and most aggressive form, accounting for approximately 10% of cases. These tumors have cells that appear highly abnormal and lack clear structural organization, which makes them more likely to spread rapidly.

How is Synovial Sarcoma Diagnosed? 

Synovial sarcoma is typically diagnosed using a combination of imaging, biopsy, and, increasingly, advanced genetic testing. These tools are critical in confirming the diagnosis, understanding the tumor’s characteristics, and guiding treatment decisions.

  • Imaging Tests:
    • MRI and CT scans are used to determine the size, location, and extent of the tumor. These imaging techniques help doctors assess whether the tumor is invading nearby tissues and plan the most effective surgical or treatment approach.
    • PET scans are used to detect cancer activity in the body. PET scans are particularly helpful in identifying areas of metastasis and monitoring the effectiveness of treatment.
  • Biopsy: A biopsy involves taking a sample of the tumor to confirm the presence of synovial sarcoma. The most definitive feature of this cancer is the presence of the SS18-SSX fusion gene, which is found in nearly all cases. A biopsy can be performed using a core needle biopsy (minimally invasive) or a surgical biopsy (removing a larger tissue sample). Because synovial sarcoma can resemble other soft tissue tumors, it is crucial to analyze the biopsy sample at a specialized sarcoma pathology lab.
  • Advanced DNA and Genetic Testing: Genetic and molecular testing plays an increasingly vital role in diagnosing synovial sarcoma, particularly for cases where biopsy findings are inconclusive. These tests analyze the tumor’s genetic makeup, providing precise confirmation of the disease and identifying potential treatment targets.
    • Fluorescence In Situ Hybridization (FISH): This specialized molecular test is used to detect the SS18-SSX fusion gene, which is the hallmark of synovial sarcoma. FISH uses fluorescently labeled DNA probes that attach to specific genetic sequences, allowing pathologists to visually confirm the presence of the chromosomal translocation under a microscope. It is highly specific and rapid, making it one of the most commonly used tests for diagnosing synovial sarcoma.
    • Reverse Transcription Polymerase Chain Reaction (RT-PCR): This test detects the exact fusion transcript produced by the SS18-SSX gene rearrangement. It is highly sensitive and is sometimes used alongside FISH to provide additional confirmation.
    • Next-Generation Sequencing (NGS): This broader genomic analysis can identify other genetic alterations in the tumor, which may help guide personalized treatment decisions, such as targeted therapy or immunotherapy. Some clinical trials require NGS results to determine eligibility for experimental treatments.

Sources and Additional Information

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