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 in 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.

This cancer is most frequently diagnosed in adolescents and young adults but can occur at any age. It accounts for approximately 5–10% of all soft tissue sarcomas.

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.

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.

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.

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 play a role in increasing the risk.

• Random Cellular Events: Like many cancers, synovial sarcoma may result from random errors during cell division. Occasionally, normal cellular processes can go awry, leading to mutations like the SS18-SSX fusion.

• Potential Influences of Age and Development: Synovial sarcoma is most frequently diagnosed in adolescents and young adults, suggesting a possible link 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-known risk factors, such as smoking or a family history of related conditions. This makes predicting or preventing the disease particularly challenging.

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.

Diagnosing synovial sarcoma requires a combination of imaging, biopsy, and increasingly, advanced genetic testing. These methods confirm the diagnosis, assess the tumor’s characteristics, and guide treatment decisions.

Imaging Tests
Imaging scans help doctors assess the size, location, and spread of the tumor.

• MRI (Magnetic Resonance Imaging)
  • Ideal for visualizing soft tissue tumors.
  • Provides high-resolution images to determine if the tumor is invading surrounding tissues.

• CT (Computed Tomography) Scans
  • Often used to detect metastasis, particularly in the lungs (American Cancer Society).
  • Helps doctors plan surgical and treatment approaches.

• PET (Positron Emission Tomography) Scans
  • Detects cancer activity throughout the body.
  • Helps identify areas of metastasis and monitor treatment effectiveness.

Biopsy

A biopsy is necessary to confirm the presence of synovial sarcoma. The defining genetic marker of this cancer is the SS18-SSX fusion gene, found in nearly all cases.

• Core Needle Biopsy - A minimally invasive procedure that removes a small tissue sample for analysis.
• Surgical Biopsy - A larger tissue sample is extracted for more detailed examination.

Because synovial sarcoma can resemble other soft tissue tumors, biopsy samples should be analyzed by a specialized sarcoma pathology lab.

Advanced Genetic & Molecular Testing

Genetic and molecular testing plays an increasingly vital role in diagnosing synovial sarcoma, particularly for cases where imaging and 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):
  • Detects the SS18-SSX fusion gene, the hallmark of synovial sarcoma.
  • Uses fluorescent DNA probes to confirm the genetic sequences, allowing pathologists to visually confirm the presence of the chromosomal translocation under a microscope.
  • A highly specific and rapid diagnostic tool, making it one of the most widely used methods for diagnosing synovial sarcoma.

Reverse Transcription Polymerase Chain Reaction (RT-PCR):

• Identifies the exact fusion transcript from the the SS18-SSX gene rearrangement.
• Highly sensitive and often used alongside FISH for added confirmation.

Next-Generation Sequencing (NGS):

• Provides a comprehensive genetic profile of the tumor.
• Identifies additional genetic alterations that could guide personalized treatment decisions, such as targeted therapy or immunotherapy.
• Some clinical trials require NGS results to determine eligibility for experimental treatments.

• Synovial Sarcoma Foundation Patient Survey

• Penn Medicine: Synovial Sarcoma

• Children’s Hospital of Philadelphia (CHOP): Synovial Sarcoma

• Dana-Farber Cancer Institute: Synovial Sarcoma

• National Cancer Institute: Synovial Sarcoma