Synovial Sarcoma

Synovial sarcoma, also known as malignant synovioma, is a rare form of soft-tissue sarcoma that primarily affects the extremities of the arms or legs, often near joint capsules and tendon sheaths. Despite its name, the tumour does not necessarily originate from synovial cells. The exact cellular origin remains unknown.

This malignancy can also occur in other tissues and organs, including the brain, prostate, and heart. Synovial sarcoma has an incidence rate of about 1-2 per 1,000,000 people annually and is most common in the third decade of life, with a slightly higher prevalence in males compared to females (ratio approximately 1.2:1).

Overview

Synovial sarcoma typically presents as an asymptomatic swelling or mass. General symptoms associated with malignancies, such as fatigue, may occasionally be reported. The tumour's location near joints can sometimes cause discomfort or restricted movement, although pain is not a common initial symptom.

Signs and Symptoms

Synovial sarcoma typically presents as an asymptomatic swelling or mass. General symptoms associated with malignancies, such as fatigue, may occasionally be reported. The tumour's location near joints can sometimes cause discomfort or restricted movement, although pain is not a common initial symptom.

Diagnosis

Histopathology

The diagnosis of synovial sarcoma is usually based on histological examination and confirmed by identifying the t(X;18) chromosomal translocation. Microscopically, two cell types can be observed: spindle or sarcomatous cells, which are small and uniform, and epithelial cells. Classical synovial sarcoma exhibits a biphasic appearance with both cell types present. However, it can also appear as poorly differentiated or monophasic fibrous, consisting solely of spindle cells. There is a rare monophasic epithelial form that complicates differential diagnosis.

There is no universal grading system for reporting histopathology results for synovial sarcoma. In Europe, the Trojani system is gaining popularity, whereas the NCI grading system is more common in the United States. The Trojani system scores the sample based on tumour differentiation, mitotic index, and tumour necrosis, converting this into a grade between 1 and 3. The NCI system also uses a three-grade scale but incorporates additional factors.

Immunohistochemistry (IHC) plays a very important role in diagnosis. SS18-fusion specific antibody and SSX-CT antibody are highly sensitive and specific for synovial sarcoma. Cytokeratin is typically expressed, at least focally. TLE1, BCL2, and CD99 may be positive but lack specificity.

Molecular Biology

Most cases of synovial sarcoma are associated with a reciprocal translocation t(x;18)(p11.2;q11.2), resulting in the SS18-SSX fusion gene. This fusion protein involves the transcriptional activating domain of SS18 and the transcriptional repressor domains of SSX, incorporating into the SWI/SNF chromatin remodelling complex, a known tumour suppressor. The SS18-SSX fusion gene is believed to underlie synovial sarcoma pathogenesis through dysregulation of gene expression. There is some association between the SS18-SSX1 or SS18-SSX2 fusion type and both tumour morphology and five-year survival rates.

Treatment

Treatment for synovial sarcoma is typically multimodal, involving surgery, chemotherapy, and radiotherapy:

• Surgery: The primary treatment modality involves surgically removing the tumour along with a margin of healthy tissue. Surgery is curative in approximately 20–70% of patients, depending on the study.
• Chemotherapy: Conventional chemotherapy, such as doxorubicin hydrochloride and ifosfamide, is used to reduce microscopic metastases. Although the benefit of chemotherapy on overall survival is unclear, recent studies suggest marginal improvements in patients with advanced, poorly differentiated disease.
• Radiotherapy: Radiotherapy aims to reduce the chance of local recurrence. The benefit of radiotherapy is less clear than that of chemotherapy.

Synovial sarcoma remains a challenging cancer to treat due to its complexity and rarity, and ongoing research aims to improve diagnostic and therapeutic strategies.

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Self-assessment MCQs (single best answer)

What is the incidence rate of synovial sarcoma annually?

Which decade of life is synovial sarcoma most common?

What is the male-to-female prevalence ratio for synovial sarcoma?

Which chromosomal translocation is associated with synovial sarcoma?

What is the primary treatment modality for synovial sarcoma?

Which immunohistochemical marker is typically expressed in synovial sarcoma?

What role does radiotherapy play in the treatment of synovial sarcoma?

Which grading system is more commonly used in the United States for reporting histopathology results of synovial sarcoma?

What is the significance of the SS18-SSX fusion gene?

What are the two cell types observed microscopically in classical synovial sarcoma?