Synovial Sarcoma - Pathology

summary
- Synovial Sarcoma is a malignant, soft tissue sarcoma caused by a t(X;18) chromosomal translocation mutation 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 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 radiation.

Epidemiology
- Demographics
  - most common sarcoma found in young adults (15-40 years)
  - affects more males than females
- Anatomic location
  - it is the most common malignant sarcoma of the foot

                        Etiology
                    
                        Mechanism
                    
                        cellular origin of synovial sarcoma is unknown, but it is not the synovial cell or any cell involved in the synovium
                    
                        the name synovial sarcoma is a misnomer.
                    
                        Pathophysiology
                    
                        metastasis
                    
                        synovial sarcoma typically shows high histologic grade
                    
                        metastasis may develop in 30-60% of patients
                    
                        like other sarcomas, the lung is most common site of metastasis
                    
                        synovial sarcoma is one of the rare soft tissue sarcomas which can metastasize to lymph nodes 
                    
                        the other sarcomas which can metastasize to lymph nodes include
                    
                        angiosarcoma
                    
                        clear cell sarcoma
                    
                        rhabdomyosarcoma
                    
                        epithelioid sarcoma
                    
                        can stage with 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
                    
                                            SYT-SSX1 vs. SYT-SSX2
                                        
                                            SYT-SSX1

                                            SYT-SSX2
                                        
                                            Frequency
                                        
                                            More common (60% of tumors)
                                        
                                            Less common (40% of tumors)
                                        
                                            Histology type
                                        
                                            Biphasic
                                        
                                            Monophasic
                                        
                                            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 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
- Radiographs
  - can show soft tissue mineralization (calcification) in these tumors
  - may resemble heterotopic ossification
- CT
  - can show calcification in the soft tissue mass
- MRI
  - MRI reveals a heterogenous mass that is typically dark on T1 weighted images and bright on T2 weighted images

Histology
- Characteristic findings
  - classical synovial sarcoma shows a biphasic appearance with two typical cell types
    
    spindle cells (fibrous type of cells)
    
    relatively small and uniform and found in sheets of malignant appearing cells with minimal cytoplasm and dark atypical nuclei
    
    epithelial cells
    
    gland, nest, or cyst-like cells
  - rarely, synovial sarcoma can also present with poorly differentiated or monophasic fibrous cell histology, consisting only of sheets of spindle cells
  - cellular origin of synovial sarcoma is unknown, but it is not the synovial cell or any cell involved in the synovium. The name SYNOVIAL sarcoma is a misnomer
- Immunostaining for
  - synovial sarcoma stains positive for
    
    vimentin
    
    epithelial membrane antigen
    
    sporadic S-100
    
    epithelial cells stain positive for keratin

Treatment
- Operative
  - wide surgical resection with adjuvant radiotherapy
    
    indications
    
    standard of care in most patients
    
    technique
    
    radiotherapy
    
    may be delivered either pre-surgery or post-surgery
    
    chemotherapy
    
    data regarding chemotherapy in synovial sarcoma suggests that chemotherapy may improve both local control and overall survival

Prognosis
- Overall prognosis is poor
  - 5 year survival is approximately 50%
  - 10 year survival is approximately 25%
- SYT-SSX fusion type is most important prognostic factor
  - SYT-SSX2 better survival

SYT-SSX1 vs. SYT-SSX2
	SYT-SSX1	SYT-SSX2
Frequency	More common (60% of tumors)	Less common (40% of tumors)
Histology type	Biphasic	Monophasic
Gender	M:F = 1:1	M:F = 1:2
Presentation	Larger, with metastases	Smaller, without metastases
Survival	Worse	Better