Summary Synovial Sarcoma is a malignant, soft tissue sarcoma caused by a t(X;18) chromosomal translocation mutation ( SS18:SSX fusion protein) most commonly found near joints but rarely within the joint. The condition usually presents in patients between 15 and 40 years old with a growing mass in proximity to a joint. Diagnosis is made with a biopsy showing a classic mono/biphasic appearance with atypical spindle cells and epithelial cells. Immunostaining is positive for epithelial membrane antigen and vimentin. Treatment is usually wide surgical excision with perioperative radiation. Epidemiology Demographics 5-10% of all soft tissue sarcomas most common sarcoma found in adolescent age group affects males and females almost equally (1.2 to 1) More common in the lower limbs most commonly around the knee - popliteal fossa it is the most common sarcoma of the foot Etiology Mechanism mesenchymal soft tissue sarcoma with unknown cellular origin synovial sarcoma is a misnomer due to the tumor's microscopic resemblance to mature synovium Pathophysiology synovial sarcoma typically shows high histologic grade metastasis metastasis may develop in 30-60% of patients like other sarcomas, the lung is most common site of metastasis synovial sarcoma has been shown to have similar rates of lymph node metastasis compared to other soft tissue sarcomas i.e angiosarcoma, clear cell sarcoma, rhabdomyosarcoma, epithelioid sarcoma can stage with lymph node biopsy - called sentinel lymph node biopsy while lymph node metastasis is a poor prognostic sign, it is not as bad as lung metastasis metastasis is more common with large, deep, and high grade sarcomas Genetics chromosomal translocation t(X;18) is observed in more than 90% of cases translocation forms the SYT-SSX1, 2, or 4 fusion protein SYT-SSX4 is rare fusion proteins bind to BAF complex, which displaces the tumor suppressor BAF47 new BAF complex activates Sox2, which leads to tumor formation SYT-SSX1 vs. SYT-SSX2 SYT-SSX1 SYT-SSX2 Frequency More common (60% of tumors) Less common (40% of tumors) Histology type Biphasic (contains both spindle cells and epithelial cells) Monophasic (contains either spindle cells OR epithelial cells) Gender M:F = 1:1 M:F = 1:2 Presentation Larger, with metastases Smaller, without metastases Survival Worse Better Presentation Symptoms typically present as a slow growing mass in proximity to a joint may be painless or painful most commonly occur in periarticular locations knee, shoulder, elbow, foot 60% are found in the lower extremity Physical exam check for regional lymphadenopathy Imaging Ultrasound nonspecific heterogenous hypoechoic mass Radiographs can show soft tissue mineralization (calcification) in these tumors may resemble heterotopic ossification CT Well circumscribed mass can show calcification in the soft tissue mass CT chest for staging MRI Gold standard for diagnostic imaging MRI reveals a heterogenous mass that is typically dark on T1 weighted images and bright on T2 weighted images T2 "triple sign" areas of high signaling form necrosis/cystic degeneration and low signaling from calcifications and fibrosis Staging Biopsy core-needle versus incisional biopsy FNA is not gold-standard as it does not provide information on tumor structure CT Chest PET/CT Scan Histology Characteristic findings classical synovial sarcoma shows a mono/biphasic appearance with two typical cell types spindle cell type is most common relatively small and uniform and found in sheets of malignant appearing cells with minimal cytoplasm and dark atypical nuclei epithelial cell type gland, nest, or cyst-like cells cellular origin of synovial sarcoma is unknown Immunostaining synovial sarcoma stains positive for vimentin epithelial membrane antigen sporadic S-100 epithelial cells stain positive for keratin Treatment Operative wide surgical resection with perioperative radiotherapy indications standard of care in most patients technique radiotherapy may be delivered in neoadjuvant or adjuvant fashion no consensus as to which provides better outcomes decreases the rate of local recurrence and improves overall survival and disease-specific survival chemotherapy data regarding chemotherapy in synovial sarcoma suggests that chemotherapy may improve both local control and overall survival routine use is limited and there is no consensus for regimen or timing of chemotherapy Reserved for high risk tumors, metastatic disease, and younger populations Prognosis Overall prognosis is poor 5 year survival is approximately 50-60% 10 year survival is approximately 25% Prognostic factors include size, grade, location, patient age, and surgical margins SYT-SSX fusion type is most important prognostic factor SYT-SSX2 better survival