Synovial Sarcoma

Synovial sarcoma is a high-grade soft tissue sarcoma that makes up 5 to 10% of soft tissue sarcomas. Despite its name, it does not arise from synovium. Most patients are 15 to 40 years old. About 70 to 80% occur in the extremities near large joints (the knee is the most common), and the rest in the head and neck, trunk and retroperitoneum.

The defining lesion is a fusion of SS18 to SSX1, SSX2 or SSX4 from t(X;18), which is present in over 95%. Histology: monophasic (spindle cells), biphasic (epithelial and spindle cells) and poorly differentiated. Metastases develop in 30 to 50%, mainly to the lung, with a pattern of late recurrence years after treatment. Regional lymph node spread is uncommon (about 5%).

Five-year survival is about 60 to 70%, with a worse outlook for tumors over 5 cm, poor differentiation, truncal and head-neck sites, and age over 20. Complications: local recurrence, pulmonary metastases and neurovascular compression.

• A slowly growing deep mass near a joint, often present for years before diagnosis
• Pain or tenderness in about half
• Neurovascular compression, joint limitation and rarely a mass in the pharynx or lung
• Cough and breathlessness from pulmonary metastases
• Red flags: rapid growth, size over 5 cm, deep location, a mass in a young patient that was dismissed as benign

1. Radiographs: a soft tissue mass with calcification in about 30%.
2. MRI with gadolinium: a heterogeneous mass, with a classic triple signal (hyperintense, intermediate and hypointense areas), hemorrhage and septations.
3. Core needle biopsy along the future surgical tract. Immunohistochemistry: TLE1, epithelial membrane antigen, cytokeratin and BCL2 positivity.
4. Molecular confirmation: SS18 break-apart FISH or SS18-SSX RT-PCR, which is diagnostic.
5. Staging: CT chest (and whole body PET-CT or CT of abdomen when indicated).

Differentials: malignant peripheral nerve sheath tumor, fibrosarcoma, Ewing sarcoma, pigmented villonodular synovitis, ganglion, hemangioma, epithelioid sarcoma.

• Limb-sparing wide excision with negative margins in a multidisciplinary sarcoma centre. Avoid unplanned excision.
• Prophylaxis: cefazolin 2 g IV before incision (3 g if over 120 kg), and enoxaparin 40 mg SC daily while mobility is reduced.
• Radiotherapy: preoperative 50 Gy in 25 fractions, or postoperative 60 to 66 Gy in 30 to 33 fractions for positive margins, to improve local control.
• Chemotherapy (this tumor is relatively chemosensitive) for tumors over 5 cm, deep high-grade tumors and metastatic disease:
  • Doxorubicin 75 mg/m2 IV on day 1 with ifosfamide 2.5 g/m2 IV daily on days 1 to 4 and mesna at 100% of the ifosfamide dose, every 21 days for 4 to 6 cycles, with filgrastim 5 micrograms/kg SC daily.
  • Monitor echocardiogram, creatinine, blood count, and neurotoxicity.
  • Second line: pazopanib 800 mg orally once daily (check blood pressure, thyroid function and liver tests), trabectedin 1.5 mg/m2 IV over 24 hours every 21 days, or high-dose ifosfamide 14 g/m2 over 14 days.
• Isolated pulmonary metastases: metastasectomy, or stereotactic ablative radiotherapy 50 Gy in 5 fractions.
• Targeted T cell therapy for advanced HLA-A*02 positive disease with MAGE-A4 expression is available in specialist centres.

Follow-up: MRI of the primary and CT chest every 3 months for 2 years, every 6 months to year 5, then yearly. Counsel on late recurrence and on fertility.