Synovial Sarcoma: Symptoms, Types, Causes and Treatment

Synovial sarcoma is a rare but aggressive cancer that typically affects the soft tissues near joints, especially in adolescents and young adults. Despite its name, it does not arise from synovial tissue but from mesenchymal cells, and it can develop almost anywhere in the body. Early recognition and accurate diagnosis are crucial, as the disease can be subtle and variable in presentation. This article provides an in-depth look at the symptoms, types, causes, and treatment options for synovial sarcoma, synthesizing the latest research and clinical insights.

Symptoms of Synovial Sarcoma

Synovial sarcoma can be challenging to spot early on because its symptoms often mimic benign conditions or other types of soft tissue tumors. Awareness of the range of possible symptoms is essential for early detection and timely intervention.

Symptom	Description	Frequency/Note	Source(s)
Mass/Lump	Painless or painful swelling, often slow-growing	Most common, often <5 cm at first	1,2,10
Pain	Can be present or absent	Sometimes the only symptom	1,6
No Mass	Some patients present without a palpable mass	Up to 30% of cases	1
Joint Contracture	Restricted movement or stiffness near a joint	Seen in ~21% of pediatric cases	1
Other	Unexplained swelling, tenderness, or local symptoms	Variable, can mimic benign lesions	1,2

Table 1: Key Symptoms

Overview of Symptom Presentation

The presentation of synovial sarcoma is diverse, making diagnosis tricky. The most common symptom is a soft tissue mass or lump, which is often painless and slow-growing. This lump can occur near large joints, particularly in the legs or arms, but may be present in other locations as well 1,2. Notably, nearly half of children with synovial sarcoma in one study had a painless mass, and about a third presented with no detectable mass at all 1.

Common and Uncommon Symptoms

• Painless Mass: The hallmark finding, especially in young people. Its slow growth often leads to delayed medical attention 1,2.
• Pain: While pain may be present, it is not universal. When present, it is often mild, leading to further diagnostic delays 1,6.
• No Mass: In some cases, especially in children, no mass is detectable, and symptoms may instead be joint-related or nonspecific 1.
• Joint Contracture: Some patients experience restricted range of motion or joint stiffness, sometimes in the absence of a discernible mass. This is particularly seen in pediatric patients 1.
• Other Signs: Swelling, tenderness, or unexplained local symptoms may be present. Synovial sarcomas can also mimic benign lesions due to their slow growth and well-defined margins 2.

Diagnostic Delays

The variety of symptoms, combined with their indolent nature, often leads to significant delays in diagnosis. Studies show that both patient and healthcare provider delays are common, sometimes stretching over months or even years 1,2.

Types of Synovial Sarcoma

Understanding the different types of synovial sarcoma is key for pathologists and oncologists, as the subtype can influence treatment decisions and prognosis.

Type	Morphology/Features	Prevalence	Source(s)
Monophasic	Spindle cells, lacks glandular/epithelial areas	Most common (~32%)	3,4,5
Biphasic	Both spindle and epithelial (glandular) cells	~20%	3,4,5
Poorly Differentiated	High-grade, aggressive, variable morphology	Rare	3,5
Epithelioid	Predominantly epithelial appearance	Very rare (<1%)	4

Table 2: Synovial Sarcoma Types

Monophasic Synovial Sarcoma

This is the most frequently encountered type, characterized by uniform spindle cells arranged in fascicles. There is little to no obvious epithelial/glandular component when viewed under a microscope. Diagnosis often relies on immunohistochemistry and genetic analysis 3,5,6.

Biphasic Synovial Sarcoma

Biphasic synovial sarcomas display both spindle (sarcomatous) and epithelial (glandular) cells. This classic pattern makes diagnosis more straightforward but is less common than the monophasic type 3,4.

Poorly Differentiated and Epithelioid Types

• Poorly Differentiated: These tumors have aggressive behavior, with high-grade features and marked cellular atypia. They can be seen in both monophasic and biphasic backgrounds 3,5.
• Epithelioid: Extremely rare, these tumors have a predominance of epithelial-like cells and are associated with a poorer prognosis 4.

Clinical Relevance of Subtypes

The subtype and grade of synovial sarcoma can influence both prognosis and treatment options. For example, poorly differentiated and epithelioid types tend to behave more aggressively and may require more intensive therapy 4,5,10.

Causes of Synovial Sarcoma

The root cause of synovial sarcoma lies in a well-characterized genetic abnormality, making it unique among many soft tissue sarcomas.

Cause	Mechanism/Description	Key Details	Source(s)
t(X;18) Translocation	Chromosomal fusion between SS18 and SSX1/2/4	Found in >90% of cases; pathognomonic	3,5,7,10,11
SS18-SSX Fusion Protein	Alters gene regulation via epigenetic disruption	Drives tumor formation	7,9,11
Risk Factors	Age 15–40, male sex, extremity location	Young adults most affected	4,7,11
Other Causes	No known environmental or inherited risk	Not associated with synovial tissue	3,5

Table 3: Key Causes and Risk Factors

Chromosomal Translocation t(X;18)

Synovial sarcoma is defined by a specific chromosomal translocation: t(X;18)(p11.2;q11.2). This results in the fusion of the SS18 gene on chromosome 18 with one of the SSX genes (usually SSX1 or SSX2) on the X chromosome. The resulting SS18-SSX fusion protein disrupts normal cell regulation and leads to cancer formation 3,5,7,10,11.

Molecular Mechanism

The SS18-SSX fusion protein alters the function of multi-protein complexes that control the epigenetic landscape of the cell, including the SWI/SNF (BAF) complex and Polycomb Repressive Complexes (PRC1/2), resulting in aberrant gene expression and unregulated cell growth 7,9,11.

Demographic and Anatomic Risk Factors

• Age and Gender: Most cases occur in adolescents and young adults (ages 15–40), with a slight male predominance 4,7,11.
• Location: Although “synovial” is in the name, the tumor most often arises near, but not within, large joints—especially the knees, feet, and arms. It can also appear in the head/neck or, rarely, in the lungs and other unusual sites 2,5,6.
• No Known Environmental or Inherited Risk: There are currently no identified environmental exposures, lifestyle factors, or inherited genetic syndromes linked with synovial sarcoma 3,5.

Why the Name “Synovial Sarcoma”?

Despite its name, synovial sarcoma does not originate from synovial cells. Instead, it arises from primitive mesenchymal cells capable of both mesenchymal and epithelial differentiation, explaining its varied histological appearance 3,5.

Treatment of Synovial Sarcoma

Treatment for synovial sarcoma is complex and often requires a multidisciplinary approach. Current therapies aim both to remove or shrink the tumor locally and to address the risk of metastasis.

Treatment	Description/Strategy	Role/Effectiveness	Source(s)
Surgery	Wide local excision/removal	Cornerstone for local control	5,7,10,12
Radiotherapy	Pre- or post-operative targeted radiation	Improves local control, survival benefit in some	4,7,9,10
Chemotherapy	Ifosfamide, doxorubicin, trabectedin, pazopanib	Used in high-risk/metastatic cases; relative chemosensitivity	7,9,12,14,15
Targeted/Novel Therapies	Immunotherapy, epigenetic, kinase, DNA damage response inhibitors	Experimental/clinical trials	7,8,9,13,15

Table 4: Main Treatment Options

Surgery

Wide surgical excision with negative margins is the primary treatment for localized synovial sarcoma. Surgery aims to completely remove the tumor and any surrounding tissue that may harbor microscopic disease 5,7,10,12. In the head and neck or other complex anatomical areas, surgery can be particularly challenging 6.

Radiotherapy

Radiation therapy is frequently used either before or after surgery, especially for larger or deeper tumors. It reduces the risk of local recurrence and can improve survival outcomes in some patient groups 4,7,9,10. In pediatric patients, the side effects of radiation must be carefully weighed against the benefits 11.

Chemotherapy

Synovial sarcoma is more responsive to chemotherapy than many other soft tissue sarcomas, though responses are variable. Commonly used drugs include:

• Ifosfamide
• Doxorubicin
• Trabectedin
• Pazopanib (especially in advanced/metastatic cases)

Combination regimens (e.g., ifosfamide plus doxorubicin) are often used in high-risk or metastatic disease. However, the overall benefit of chemotherapy, particularly in adults with localized disease, remains a matter of debate 7,12,14,15.

Emerging and Experimental Therapies

Newer therapies are under investigation, including:

• Targeted Therapy: Agents directed at the SS18-SSX fusion protein or its downstream pathways, such as epigenetic modulators and kinase inhibitors 7,8,9,13.
• Immunotherapy: Approaches to stimulate the immune system against the tumor, including peptide vaccines targeting the fusion protein 5,7.
• DNA Damage Response Inhibitors: Drugs like ATR inhibitors have shown promise in preclinical studies, especially in combination with standard chemotherapy 13,15.
• Clinical Trials: Participation in clinical trials is encouraged, as outcomes for advanced or metastatic synovial sarcoma remain poor with current treatments 7,14.

Prognosis and Follow-Up

Prognosis depends on several factors, including tumor size, location, patient age, and subtype. Smaller tumors and younger patient age are associated with better outcomes. Poorly differentiated and epithelioid subtypes, larger tumors, older age, and non-extremity locations predict worse survival 4,10,11. Five-year survival rates for localized disease can range from 40% to 90%, but metastatic disease has a much poorer outlook 14.

Conclusion

Synovial sarcoma is a rare and complex cancer that requires high clinical suspicion for diagnosis and an expert, multidisciplinary approach for treatment. Advances in molecular biology are opening new doors to targeted therapies, but early detection and timely intervention remain critical. Here’s a summary of the main points:

• Symptoms are highly variable, most commonly a painless, slow-growing mass near a joint, but can also include pain, joint contracture, or no mass at all.
• Three main types exist: monophasic, biphasic, and poorly differentiated, each with distinct histological features and implications for treatment.
• The cause is a specific genetic translocation (t(X;18)), resulting in a fusion gene that drives tumor development through epigenetic changes.
• Treatment is multidisciplinary, centering on surgery with radiotherapy and/or chemotherapy as needed; new targeted therapies are in development but not yet standard.

If you or someone you know has unexplained swelling, a persistent lump near a joint, or joint stiffness, especially in adolescence or young adulthood, early evaluation by a healthcare professional is essential. Ongoing research promises hope for more effective and personalized therapies in the future.