Synovial Sarcoma

Author: Patrick O'Donnell

Topic updated on 04/23/13 9:56pm

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
Metastatsis
- 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 metastatize 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%

Presentation

Symptoms
- typically present as a growing mass in proximity to a joint
- may be painless or painful
- most commonly occur in para-articular locations
  - knee, shoulder, elbow, foot
  - 60% are found in the lower extremity
Physical exam
- examen 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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Qbank (7 Questions)

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

Review Topic

1. BCR-ABL
2. SYT-SSX
3. EWS-FLI1
4. FUS-CHOP
5. COL1A1-PDGFB

PREFERRED RESPONSE ▶

DISCUSSION: 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

REFERENCES:

1. Tornkvist M, Brodin B, Bartolazzi A, Larsson O. A novel type of SYT/SSX fusion: methodological and biological implications. Mod Pathol. 2002 Jun;15(6):679-85. PMID:12065783 (Link to Abstract)

2. Yuan J, Fuchs B, Scully S. Molecular basis of cancer. In: Einhorn TA, O'Keefe RJ, Buckwalter JA, eds. Orthopaedic Basic Science: Foundations of Clinical Practice. 3rd ed. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2007:379-393.

Question Authors:

Patrick O'Donnell MD/PhD, John Badylak MD, Ben Taylor MD,

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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? Topic

Review Topic

FIGURES: A

1. Osteosarcoma
2. Morton's neuroma
3. Synovial sarcoma
4. Fibrous dysplasia
5. Desmoid tumor

PREFERRED RESPONSE ▶

DISCUSSION: 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.

REFERENCES:

1. Lewis JJ, Antonescu CR, Leung DH, Blumberg D, Healey JH, Woodruff JM, Brennan MF. Synovial sarcoma: a multivariate analysis of prognostic factors in 112 patients with primary localized tumors of the extremity. J Clin Oncol. 2000 May;18(10):2087-94. PMID:10811674 (Link to Abstract)

2. Thompson RC Jr, Garg A, Goswitz J, Cheng EY, Clohisy DR, Dusenbery K. Synovial sarcoma. Large size predicts poor outcome. Clin Orthop Relat Res. 2000 Apr;(373):18-24. PMID:10810458 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD, Guillem Lomas MD, Derek Moore,

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

Review Topic

1. Typically occur around the joints of the arm or leg
2. Immunohistochemisty is positive for cytokeratin and epithelial membrane antigen
3. Histology is named because the cell line of origin is the type II synovial cell
4. May show biphasic or monophasic histology
5. Classic age range is the younger adult < 40 years of age

PREFERRED RESPONSE ▶

DISCUSSION: 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.

Illustrations: A

REFERENCES:

1. Weiss SW, Goldblum JR. Malignant soft-tissue tumors of uncertain type, in Strauss M, Gery L (eds): Enzinger and Weiss’s Soft Tissue Tumors, ed 4. St. Louis, MO, Mosby, 2001, pp 1483-1509

2. Pradhan A, Cheung YC, Grimer RJ, Peake D, Al-Muderis OA, Thomas JM, Smith M. Soft-tissue sarcomas of the hand: oncological outcome and prognostic factors. J Bone Joint Surg Br. 2008 Feb;90(2):209-14. PMID:18256090 (Link to Abstract)

Question Authors:

Patrick O'Donnell MD/PhD,

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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? Topic

Review Topic

FIGURES: A

1. Synovial sarcoma
2. Liposarcoma
3. Malignant fibrous histiocytoma
4. Osteosarcoma
5. Chondrosarcoma

PREFERRED RESPONSE ▶

DISCUSSION: 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 5cm survived, patients with tumors between 5-10cm had a 75% survival, and patients with tumors greater than 10cm had a 20% survival.

REFERENCES:

Question Authors:

Patrick O'Donnell MD/PhD, Patrick McCulloch MD,

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

Review Topic

1. Myxoid liposarcoma
2. Synovial Sarcoma
3. Osteosarcoma
4. Ewing's Sarcoma
5. Clear cell sarcoma

PREFERRED RESPONSE ▶

DISCUSSION: 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),

REFERENCES:

1. Menendez LR: Othopaedic Knowledge Update: Musculoskeletal Tumors, Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 11-20

2. Kawai A, Woodruff J, Healey JH, Brennan MF, Antonescu CR, Ladanyi M. SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. New England Journal of Medicine, 338:153-160 PMID:9428816 (Link to Abstract)

3. Enzinger FM, Weiss SW: Soft Tissue Tumors, ed 4, St Louis, MO, Mosby, 2001, pp 1483 to 1571

Question Authors:

Jan Szatkowski MD, Michael Hughes MD,

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

Review Topic

FIGURES: A

1. Figure A
2. Figure B
3. Figure C
4. Figure D
5. Figure E

PREFERRED RESPONSE ▶

DISCUSSION: 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.

REFERENCES:

1. Scwartz HS (ed). Orthopaedic Knowledge Update: Musculoskeletal tumors 2. American Academy of Orthopaedic Surgeons. Rosemont, IL. 2007, pp 353-357

Question Authors:

Patrick O'Donnell MD/PhD,

Please Rate Educational Value!

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Groups

ABOS II: Synovial Sarcoma

General - Oral Boards Review

7/29/2011

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Evidence & References Show References

Level of Evidence 4 (Case Series)

Lewis JJ, Antonescu CR, Leung DH, Blumberg D, Healey JH, Woodruff JM, Brennan MF. Synovial sarcoma: a multivariate analysis of prognostic factors in 112 patients with primary localized tumors of the extremity. J Clin Oncol. 2000 May;18(10):2087-94. PMID:10811674 (Link to Abstract)
Thompson RC Jr, Garg A, Goswitz J, Cheng EY, Clohisy DR, Dusenbery K. Synovial sarcoma. Large size predicts poor outcome. Clin Orthop Relat Res. 2000 Apr;(373):18-24. PMID:10810458 (Link to Abstract)
Pradhan A, Cheung YC, Grimer RJ, Peake D, Al-Muderis OA, Thomas JM, Smith M. Soft-tissue sarcomas of the hand: oncological outcome and prognostic factors. J Bone Joint Surg Br. 2008 Feb;90(2):209-14. PMID:18256090 (Link to Abstract)
Kawai A, Woodruff J, Healey JH, Brennan MF, Antonescu CR, Ladanyi M. SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. New England Journal of Medicine, 338:153-160 PMID:9428816 (Link to Abstract)

Level of Evidence 5 and Other Journal Articles (includes Case Reports, Expert Opinions, Personal Observations, and Biomechanic Studies)

Tornkvist M, Brodin B, Bartolazzi A, Larsson O. A novel type of SYT/SSX fusion: methodological and biological implications. Mod Pathol. 2002 Jun;15(6):679-85. PMID:12065783 (Link to Abstract)

Textbooks

Review of Orthopaedics, 6th Edition, Mark D. Miller MD, Stephen R. Thompson MBBS MEd FRCSC, Jennifer Hart MPAS PA-C ATC, an imprint of Elsevier, Philadelphia, Copyright 2012
AAOS Comprehensive Orthopaedic Review, Jay R. Leiberman. Published by American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2009
Orthopaedic Knowledge Update 10, John M Flyn. Published by American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2011
Hoppenfeld SP. Surgical Exposures in Orthopaedics: The Anatomic Approach. Lipponcott, Williams, and Wilkins, Philadelphia, PA, Copyright 2009
Orthopaedic In-training Examination (OITE) Questions 2004-2012, American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2004-2012
Self-Assessment Examination (SAE) Questions 2004-2012, American Academy of Orthopaedic Surgeons, Rosemont IL. Copyright 2004-2012
Yuan J, Fuchs B, Scully S. Molecular basis of cancer. In: Einhorn TA, O'Keefe RJ, Buckwalter JA, eds. Orthopaedic Basic Science: Foundations of Clinical Practice. 3rd ed. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2007:379-393.
Weiss SW, Goldblum JR. Malignant soft-tissue tumors of uncertain type, in Strauss M, Gery L (eds): Enzinger and Weiss’s Soft Tissue Tumors, ed 4. St. Louis, MO, Mosby, 2001, pp 1483-1509
Menendez LR: Othopaedic Knowledge Update: Musculoskeletal Tumors, Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 11-20
Enzinger FM, Weiss SW: Soft Tissue Tumors, ed 4, St Louis, MO, Mosby, 2001, pp 1483 to 1571
Scwartz HS (ed). Orthopaedic Knowledge Update: Musculoskeletal tumors 2. American Academy of Orthopaedic Surgeons. Rosemont, IL. 2007, pp 353-357

Undefined

Lewis JJ, Antonescu CR, Leung DH, Blumberg D, Healey JH, Woodruff JM, Brennan MF. Synovial sarcoma: a multivariate analysis of prognostic factors in 112 patients with primary localized tumors of the extremity. J Clin Oncol. 2000 May;18(10):2087-94. PMID:10811674 (Link to Abstract)
Thompson RC Jr, Garg A, Goswitz J, Cheng EY, Clohisy DR, Dusenbery K. Synovial sarcoma. Large size predicts poor outcome. Clin Orthop Relat Res. 2000 Apr;(373):18-24. PMID:10810458 (Link to Abstract)
Damron TA, Beauchamp CP, Rougraff BT, et al: Soft-tissue lumps and bumps. Instr Course Lect 2004; 53: 625-637.
Rydholm A, Berg NO, Gullberg B, et al: Epidemiology of soft-tissue sarcoma in the locomotor system: A retrospective population-based study of inter-relationships between clinical and morphologic variables. Acta Pathol Microbiol Immunol Scand [A] 1984; 92: 363-374.

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Synovial Sarcoma

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