http://upload.orthobullets.com/topic/8052/images/Case B - axilla - xray - parsons_moved.jpg
http://upload.orthobullets.com/topic/8052/images/Case B - axilla - MRI - parsons_moved.jpg
http://upload.orthobullets.com/topic/8052/images/Histology C - parsons_moved.jpg
http://upload.orthobullets.com/topic/8052/images/Case C - leg -ct - parsons_moved.jpg
http://upload.orthobullets.com/topic/8052/images/Histology A_moved.jpg
http://upload.orthobullets.com/topic/8052/images/Histology B - Parsons_moved.png

Introduction
  • Malignant soft tissue sarcoma which arises near joints, but rarely within the joint
    • 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.
  • Epidemiology  
    • demographics
      • most common sarcoma found in young adults (15-40 years) 
      • affects more males than females
    • location
      • it is the most common malignant sarcoma of the foot 
  • 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
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
 

  • Metastases
    • 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, epitheliod sarcoma, angiosarcoma, rhabdomyosarcoma, clear cell 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
  • 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
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
    • examine 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
IBank
  Location
Xray
Xray
CT
B. Scan
MRI
MRI
Histo(1)
Case A
pelvis
 
 
 
Case B
axilla
 
 
 
Case C
leg
 
 
 
 
Case D
             
(1) - histology does not always correspond to clinical case 


 

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Questions (8)

(OBQ13.17) Which of the following tumors associated with the fusion protein SYT-SSX1 can metastasize via the lymph nodes? Review Topic

QID:4652
1

Alveolar rhabdomyosarcoma

3%

(74/2376)

2

Epitheliod sarcoma

4%

(90/2376)

3

Clear cell sarcoma

5%

(120/2376)

4

Angiosarcoma

2%

(56/2376)

5

Synovial sarcoma

85%

(2024/2376)

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

Synovial sarcoma is associated with the fusion protein SYT-SSX1 and can metastasize to the lymph nodes

Synovial sarcoma is the result of the chromosomal translocation t(X:18) in greater than 90% of cases. This yields the fusion protein SYT-SSX1. Given that synovial sarcomas have a high histologic grade, they have a rate of metastasis (between 30-60%). Despite this, the lungs remain the most common site for metastatic spread.

Riad et al. evaluated the correlation between lymph node involvement and disease survival in soft tissue sarcomas. Those with isolated lymph node metastases had a 4-year survival rate of 71%. They found that 5-year survival was 57% in patients who had lymph node resections. They note that long-term survival can be achieved with lymph node resection in the presence of soft-tissue sarcomas.

Illustration A shows an axial MRI sequence of a synovial sarcoma below the cuboid of the foot. Illustration B shows a histologic evaluation of a synovial sarcoma. Note the uniform spindle cells in sheets, consistent with monophasic synovial sarcoma.

Incorrect Answers:
Answer 1, 2, 3, 4: While these sarcomas can have lymphatic involvement, none of these choices are associated with the SYT-SSX1 fusion protein.

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(OBQ11.98) Which of the following fusion proteins is associated with synovial sarcoma? Review Topic

QID:3521
1

BCR-ABL

1%

(13/1706)

2

SYT-SSX

91%

(1556/1706)

3

EWS-FLI1

3%

(50/1706)

4

FUS-CHOP

2%

(28/1706)

5

COL1A1-PDGFB

3%

(53/1706)

Select Answer to see Preferred Response

PREFERRED RESPONSE 2

The t(X;18) chromosomal translocation is commonly associated with synovial sarcoma. This chromosomal translocation forms a common fusion protein seen in synovial sarcoma, the SYT-SSX protein. There are several different forms of the SYT-SSX fusion protein seen in synovial sarcoma - where either the SSX1, SSX2, or SSX4 genes combine with the SYT gene product.

Tornkvist et al describe the molecular analysis used in the pathological diagnosis of synovial sarcoma. Using specific PCR primers directed against the fusion protein seen in synovial sarcoma, they have increased both the sensitivity and specificity of this molecular diagnosis.

The incorrect answers are associated with the following disease conditions:
BCR-ABL: the Philadelphia chromosome is seen in CML
EWS-FLI1: Ewing's sarcoma
FUS-CHOP: Myxoid liposarcoma
COL1A1-PDGFB: Dermatofibrosarcoma protuberans


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(OBQ08.15) A 22-year-old female has a painful foot mass. Clinical photo, MRI, and histology slide are shown in Figures A through C. What is the most likely diagnosis? Review Topic

QID:401
FIGURES:
1

Osteosarcoma

1%

(11/1896)

2

Morton's neuroma

2%

(31/1896)

3

Synovial sarcoma

61%

(1150/1896)

4

Fibrous dysplasia

4%

(73/1896)

5

Desmoid tumor

33%

(628/1896)

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

The clinical photo, MRI, and histology slide are consistent with a diagnosis of synovial sarcoma, one of the most common soft tissue sarcomas of the foot/ankle. Despite the name "synovial sarcoma," these tumors do not occur inside joints or in relation to the synovial tissue. Rather, they occur in peri-articular locations of the lower extremity over 60% of the time. The pathology section shows the classic epithelial cells in gland like structures with associated elongated spindle cells, classic for synovial sarcoma. The common translocation X:18 is associated with synovial sarcoma and the fusion of the SYT and SSX gene products.

Lewis et al evaluated prognostic factors in 112 patients with synovial sarcoma treated at their institution. They found that tumor size greater than 5cm or bone/neurovascular invasion were all independent adverse predictors of distant recurrence and mortality.

In a related study, Thompson et al retrospectively evaluated 38 patients with biopsy proven synovial sarcoma. In their cohort, they too found a strong association between tumor size and patient survival.


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(OBQ08.236) All of the following statements regarding synovial sarcoma are correct EXCEPT? Review Topic

QID:622
1

Typically occur around the joints of the upper or lower limb

10%

(35/341)

2

Immunohistochemisty is positive for cytokeratin and epithelial membrane antigen

10%

(34/341)

3

Histology is named because the cell line of origin is the type II synovial cell

60%

(205/341)

4

May show biphasic or monophasic histology

8%

(27/341)

5

Classic age range is the younger adult < 40 years of age

11%

(38/341)

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PREFERRED RESPONSE 3

The cell of origin in synovial sarcoma is unknown. These tumors occur arounds the joints of the arm or leg and typically occur in younger adults < 40 years of age (Illustration A shows a classic MRI of a synovial sarcoma around the knee). They are one of the most common malignant soft tissue sarcomas of the hand. They show either a monophasic or biphasic histology (Illustration B shows the biphasic histology with epithelial and spindle cell components). The immunohistochemistry can be positive for cytokeratin, vimentin, sporadic S-100, and epithelial membrane antigen.

Pradhan evaluated the oncological outcome of 63 patients with soft tissue sarcomas of the hand and found that the margin of excision (amputation, wide, marginal, or intralesional) was directly related to the risk of both local recurrence and distant metastasis.

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(OBQ05.16) A 33-year-old male presents with a painful mass in his axilla. Radiographs, MRI, and histology are shown in Figures A-C. The tumor stains positive for vimentin and epithelial membrane antigen on immunohistochemistry. What is the most likely diagnosis? Review Topic

QID:53
FIGURES:
1

Synovial sarcoma

63%

(557/886)

2

Liposarcoma

9%

(84/886)

3

Malignant fibrous histiocytoma

25%

(220/886)

4

Osteosarcoma

1%

(5/886)

5

Chondrosarcoma

2%

(16/886)

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

The clinical presentation, images, and histology are consistent with synovial sarcoma. Liposarcomas have a soap bubble appearance on histology due to the neoplastic adipose tissue. Chondrosarcomas typically show the "blue balls of cartilage" on histology, not seen here. Osteosarcomas must show the production of osteoid on histology, not seen here. While the neoplastic cells of malignant fibrous histiocytoma can look similiar on pathology, only synovial sarcoma stains for vimentin and epithelial membrane antigen. Treatment is wide surgical resection with neoadjuvant or adjuvant radiotherapy and/or chemotherapy.

Lewis et al. evaluated 112 patients with synovial sarcoma who underwent surgical resection to determine independent prognostic factors. They found overal prognosis is most directly related to tumor size and invasion of bone and neurovascular structures.

Thompson et al. evaluated a series of 38 patients with synovial sarcoma. They found a strong statistical association between size of tumor and patient survival. All patients with size less than 5 cm survived, patients with tumors between 5-10 cm had a 75% survival, and patients with tumors greater than 10 cm had a 20% survival.


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(OBQ05.72) Which of the following is the most common sarcoma found in the foot? Review Topic

QID:958
1

Epithelioid Sarcoma

12%

(232/1896)

2

Liposarcoma

2%

(44/1896)

3

Fibrosarcoma

9%

(166/1896)

4

Synovial sarcoma

75%

(1428/1896)

5

Adamantinoma

1%

(16/1896)

Select Answer to see Preferred Response

PREFERRED RESPONSE 4

Synovial sarcoma is the most common sarcoma found in the foot. It is also the most commonly found sarcoma in young adults with an average age of incidence of <30 years of age.

Synovial sarcoma is a malignant soft tissue tumor characterized by its unique (X;18)(p11;q11) chromosomal translocation. Because these tumors can grow slowly and are often associated with pain, they are sometimes misdiagnosed as a benign process, such as a ganglion cyst or bursitis. Treatment with wide surgical resection and adjuvant radiotherapy is the standard of care for these patients.

Damron et al. describe the epidemiology and clinical presentation of soft-tissue masses. They report that synovial sarcomas occur commonly in distal extremities, which include the hand, ankle and feet. They have a propensity for local recurrence and metastasis, most commonly to lung.

Scully et al. reviewed a case of 14 patients with synovial sarcoma of the foot and ankle. Ten patients had partial foot or leg amputations, and remaining had an attempted limb salvage procedure. Of the 14 patients, eight had pulmonary metastases and died of their disease.

Illustration A shows the histology of synovial sarcoma. There is an epithelial component with gland-like spaces lined by cuboidal and columnar cells

Incorrect Answers:
Answer 1: Epithelioid sarcoma is a rare tumor that most often develops in the forearm and hand. Patients are typically male in their late teens or 20's.
Answer 2: Liposarcoma is a malignant tumour that arises in fat cells, usually in deep soft tissue. They occur less frequently in the foot compared to synovial sarcoma and are very uncommon in young patients.
Answer 3: Fibrosarcoma is a malignant mesenchymal tumour derived from fibrous connective tissue. They are typically found in long or flat bones such as the femur, tibia, and mandible.
Answer 5: Adamantinoma is normally found in the diaphysis of the tibia and has a classic soap bubble appearance.

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(OBQ05.253) The chromosomal translocation t(X;18)is found in which of the following conditions? Review Topic

QID:1139
1

Myxoid liposarcoma

4%

(46/1224)

2

Synovial Sarcoma

83%

(1012/1224)

3

Osteosarcoma

2%

(29/1224)

4

Ewing's Sarcoma

7%

(87/1224)

5

Clear cell sarcoma

4%

(45/1224)

Select Answer to see Preferred Response

PREFERRED RESPONSE 2

Synovial sarcoma is a rare soft tissue sarcoma with biphasic features of both spindle cell and epithelial differentiation. Synovial sarcoma is a rare high-grade tumor that spreads along fascial planes and, thus, can be much more widespread than apparent on initial evaluation. Males are more commonly affected than females with a ratio of 1.1:1. Synovial sarcoma is characterized by a specific chromosomal translocation t(X;18)(p11;q11) that is observed in more than 90% of cases. The t(X;18)(p11;q11) translocation fuses the SYT gene from chromosome 18 to either of 2 homologous genes at Xp11, either SSX1 or SSX2. The fusion proteins SYT-SSX1 and SYT-SSX2 function as aberrant transcriptional regulators, resulting in either activation of protooncogenes or inhibition of tumor suppressor genes.

Kawai et al found that SYT-SSX fusion transcripts are a defining diagnostic marker of synovial sarcomas. These fusion transcripts may yield important independent prognostic information and provide important information for different types of treatment.

Incorrect Answers
Answer 1: Myxoid liposarcoma is associated with chromosomal translocation t(12;16)
Answer 4: Ewing's sarcoma with t(11;22)
Answer 5: Clear cell sarcoma with (12;22), Myxoid Chondrosarcoma with t(9;22),


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(OBQ04.172) Which of the following histology images represents a synovial sarcoma? Review Topic

QID:1277
FIGURES:
1

Figure A

69%

(457/666)

2

Figure B

1%

(9/666)

3

Figure C

14%

(91/666)

4

Figure D

5%

(35/666)

5

Figure E

11%

(71/666)

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PREFERRED RESPONSE 1

Figure A is the classic pattern of synovial sarcoma showing the biphasic appearance of both fibrous/spindle sarcomatous cells and epithelial cells. The high nuclear to cytoplasmic ratio and cellular atypia confirm a neoplastic process. Immunostaining of synovial sarcoma is vimentin positive and epithelial membrane antigen positive Chromosomal translocation t(X;18) is observed in more than 90% of synovial sarcoma cases and lung is most common site of metastasis. Figure B shows a Ewing's sarcoma. Figure C shows a clear cell sarcoma. Figure D shows a desmoid tumor. Finally Figure E shows fibrous dysplasia.


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