Soft tissue

Uncertain differentiation

Synovial sarcoma


Editorial Board Member: Jose G. Mantilla, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Farres Obeidin, M.D.
Borislav A. Alexiev, M.D.

Topic Completed: 13 September 2021

Minor changes: 20 September 2021

Copyright: 2003-2021, PathologyOutlines.com, Inc.

PubMed Search: Synovial sarcoma [title] soft tissue pathology free full text[sb] "last 5 years"[DP]

Farres Obeidin, M.D.
Borislav A. Alexiev, M.D.
Page views in 2020: 47,052
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Cite this page: Obeidin F, Alexiev BA. Synovial sarcoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/softtissuesynovialsarc.html. Accessed September 22nd, 2021.
Definition / general
  • Malignant soft tissue tumor of uncertain histogenesis with variable epithelial differentiation
Essential features
  • Can occur in or around any tissue in the body
  • Multiple morphologies, including monophasic spindle cell, biphasic, poorly differentiated, myxoid, ossifying and monophasic epithelial
  • Monotonous spindle cells with vesicular, plump and overlapping nuclei with hemangiopericytic vessels
  • TLE1+, cytokeratin+, EMA+, BCL2+, CD99+
  • Has a characteristic chromosomal translocation t(X;18)(p11;q11) involving genes SS18 and either SSX1, SSX2 or SSX4
Terminology
  • Obsolete terms: malignant synovioma
ICD coding
  • ICD-O: 9040/3 - synovial sarcoma, NOS
  • ICD-11: 2B5A.Y & XH9B22 - synovial sarcoma, other specified primary site & synovial sarcoma, NOS
Epidemiology
  • Accounts for 5 - 10% of all soft tissue sarcomas
  • Median age: 35
  • Age range: 0 - 85+
  • Slight male predominance (M:F = 1.2:1)
  • 17.6% of cases occur in children and young adults ages 0 - 19 (Pediatr Blood Cancer 2011;57:943)
Sites
  • Can occur anywhere in the body
  • Primary site distribution (Pediatr Blood Cancer 2011;57:943):
    • Extremities: 68.7%
    • Trunk: 15.7%
    • Head and neck: 6.3%
    • Intrathoracic: 5.3%
    • Intra-abdominal: 1.8%
    • Other: 2.2%
Pathophysiology
  • Driven by the chromosomal translocation t(X;18)(p11;q11) involving genes SS18 and either SSX1, SSX2 or SSX4
  • Translocation has multiple effects on oncogenetic pathways, including the SWI / SNF chromatin remodeling complex, polycomb repressor complex and canonical Wnt pathway (Cancer Discov 2015;5:124)
  • Translocation partner affects epithelial differentiation (Int J Clin Exp Pathol 2013;6:2272):
    • SS18-SSX1: 60 - 70% monophasic, 30 - 40% biphasic
    • SS18-SSX2: 97% monophasic, 3% biphasic
    • SS18-SSX1 inhibits Snail gene while SS18-SSX2 inhibits Slug gene (OMIM: Snail Family Transcriptional Repressor 1; SNAI1 [Accessed 9 July 2021])
    • Interfering with Snail leads to stronger derepression of E-cadherin than does interfering with Slug
    • Stronger E-cadherin and increased extracellular matrix protein MMP2 expression are needed for biphasic morphology to develop
Etiology
  • Despite the name, the cells of origin are not synovial cells
  • Histogenesis is still debated
  • 1 study has shown stem cell marker expression, suggesting that origin may be a multipotent mesenchymal stem cell (Stem Cells 2010;28:1119)
  • 1 study using mice identified satellite cells (immature myoblasts) as a potential source (Cancer Cell 2007;11:375)
Clinical features
  • Very rarely associated with prior radiation therapy (Mod Pathol 2002;15:998)
  • Not classically known to be associated with any syndromes
Diagnosis
Radiology description
  • Most present as round to oval, lobulated masses
  • Bone involvement is rare
  • Ossifying synovial sarcomas have characteristic spotty radiopacities caused by focal calcifications (Pathol Res Pract 2009;205:195)
Radiology images

Contributed by Farres Obeidin, M.D.

Elbow mass

Shoulder mass

Arm mass

Prognostic factors
Case reports
Treatment
  • Primarily surgical
  • Radiotherapy and adjuvant chemotherapy have been evaluated in high risk situations (tumors > 5 cm or difficult to resect)
  • Radiation therapy: adjuvant use has shown improvement in oncologic outcome and overall survival (J Surg Oncol 2015;111:158)
  • Adjuvant chemotherapy:
    • Data is conflicting on its use but can be considered in high risk patients
    • Ifosfamide was shown to increase disease specific survival (Ann Surg 2007;246:105)
    • 2 large European Organization for Research and Treatment of Cancer (EORTC) database clinical trials showed no benefit of doxorubicin on overall survival (Ann Oncol 2014;25:2425)
  • Novel therapies:
    • Initial PDL1 and CTLA4 studies have shown no benefit (Sarcoma 2013;2013:168145)
    • Receptor tyrosine kinase inhibitor pazopanib has a promising trend toward better overall survival
    • Tazemetostat, an EZH2 inhibitor, has also been studied in INI1 deficient tumors, including synovial sarcoma (Curr Treat Options Oncol 2018;19:13)
    • Early studies on T cell receptor based immunotherapy directed towards NY-ESO-1 in HLA-A*0201+ patients have demonstrated radiological and clinical benefit (J Clin Oncol 2011;29:917)
Gross description
  • Tumor is well circumscribed and frequently multinodular
  • Most tumors are 3 - 10 cm in greatest dimension at time of diagnosis
  • Minute lesions (< 1 cm) occur, especially in hands and feet (Am J Surg Pathol 2006;30:721)
  • Cut surface may be tan or grey, yellow or pink and soft or firm (Pathol Annu 1980;15:309)
  • Myxoid change, necrosis, calcifications and metaplastic ossification may be present
Gross images

Contributed by Farres Obeidin, M.D.

Arm mass

Shoulder mass

Lung mass

Elbow mass



Images hosted on other servers:
Missing Image

Tumor within the vastus intermedius muscle

Microscopic (histologic) description
  • General (Ann Diagn Pathol 2014;18:369):
    • 2 main subtypes: biphasic and monophasic spindle cell
    • Rarer subtypes: poorly differentiated (round cell), monophasic epithelial, calcifying / ossifying and myxoid
  • Biphasic:
    • Architecture:
      • 2 components: spindle cells and gland-like epithelial structures
      • Glandular lumina contain mucin
    • Cytologic features:
      • Epithelial component has moderate, distinct amphophilic cytoplasm with round to ovoid nuclei
      • Rarely, squamous metaplasia can occur
  • Monophasic:
    • Architecture:
      • Infiltrative borders
      • Hypercellular fascicular architecture with little intervening stroma
      • Can rarely show hyalinization or myxoid change
      • Ill defined nuclear palisading may be seen
    • Cytologic features:
      • Monotonous cells with scant amphophilic cytoplasm, ovoid to spindled vesicular nuclei with evenly dispersed chromatin and inconspicuous nucleoli
      • Nuclei often close enough to overlap with adjacent nuclei
  • Poorly differentiated: highly cellular round cells with hyperchromatic nuclei and frequent mitotic activity and necrosis
  • Additional features:
    • Characteristically features focal staghorn (or hemangiopericytic), branching vascular pattern, reminiscent of solitary fibrous tumor
    • Mast cells are common
    • Focal calcification can be seen in 33% of cases
Microscopic (histologic) images

Contributed by Farres Obeidin, M.D.

Monophasic synovial sarcoma

Hemangiopericytic vessel

Mitotic activity


Focal palisading

Posttreatment

Biphasic synovial sarcoma


Patchy
AE1 / AE3+

Weak, patchy EMA+

BCL2+

CD99+

S100+

TLE1+



Contributed by Debra Zynger, M.D.

Monophasic synovial sarcoma

Monophasic synovial sarcoma, TLE1+

Positive stains
Negative stains
Electron microscopy description
  • Glandular formation of epithelioid tumor cells with sparse luminal microvilli
Electron microscopy images

Contributed by Mark R. Wick, M.D.

Biphasic, glandular cells

Biphasic, spindle cells

Molecular / cytogenetics description
Molecular / cytogenetics images

Contributed by Mark R. Wick, M.D.

X18, in situ hybridization

Translocation in synovial sarcoma

Sample pathology report
[insert representative image here]

  • Right lower extremity, biopsy:
    • Synovial sarcoma, monophasic, FNCLCC grade 2 (see comment)
    • Comment: The tumor is composed of fascicles of bland spindle cells with sparse cytoplasm and relatively uniform, ovoid hyperchromatic nuclei and inconspicuous nucleoli. The stroma contains strands of wiry collagen. Mitoses are sparse (2 mitoses/10 high power fields). No tumor necrosis is identified. Immunohistochemically, the tumor cells are immunoreactive for CD99, EMA (subset) and TLE1, while all of the following are negative: h-caldesmon, myogenin, MyoD1, STAT6, SOX10 and WT1 (C terminus). The findings support the above diagnosis. Synovial sarcoma has a variable prognosis. Major prognostic determinants are tumor stage at presentation, tumor size and FNCLCC tumor grade.
Differential diagnosis
Board review style question #1

    Which of the following is true about the lesion pictured above?

  1. Commonly has PAX3 rearrangements
  2. It is associated with HHV8 infection
  3. It is negative for cytokeratin
  4. It occurs primarily in elderly patients
  5. SS18-SSX fusion is the characteristic chromosomal abnormality
Board review style answer #1
E. Synovial sarcoma has fusion of SS18 with SSX1, SSX2 or SSX4. It typically occurs in younger patients, with the peak incidence in the third to fourth decade and in most cases shows at least focal cytokeratin expression. It is not associated with PAX3 rearrangements, a typical finding in alveolar rhabdomyosarcoma and biphenotypic sinonasal sarcoma. HHV8 is seen in Kaposi sarcoma.

Comment Here

Reference: Synovial sarcoma
Board review style question #2
    Which morphologic feature is commonly seen in synovial sarcoma?

  1. Chicken wire calcifications
  2. Extravasated red blood cells
  3. Hemangiopericytic vessels
  4. Nuclear pleomorphism
  5. Prominent storiform pattern
Board review style answer #2
C. Hemangiopericytic vessels and monotonous nuclei are commonly seen in synovial sarcoma. Chicken wire calcifications are typically seen with chondroblastoma. Extravasated red blood cells are common in nodular fasciitis, fibromatosis and Kaposi sarcoma. A storiform pattern is characteristic of dermatofibrosarcoma protuberans.

Comment Here

Reference: Synovial sarcoma
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