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Soft Tissue Pathology 

Pathology of Synovial Sarcoma

Dr Sampurna Roy MD             





Synovial sarcoma is a well defined entity which commonly occurs in adolescents and young adults. (between 15 and 40 years of age).

This tumour is commonly located in the paraarticular regions, close to tendon  sheaths, bursae and joint capsules.

The tumour rarely involves synovial membrane.  

The hallmark tumor marker is the t(X;18) translocation, which results in fusion of the SYT gene of chromosome 18 to the SSX gene of the X chromosome, creating most frequently either an SYT-SSX1 or SYT-SSX2 transfusion transcript.


These are usually located around knee and ankle joint, as well as around hip,shoulder and elbow.

Rare variants occur in the oral cavity, anterior abdominal wall, larynx, pleura, lung, pericardium, heart and mediastinum.

Gross appearance: 

The gross appearance depends on the rate of growth and site of the tumour. 

Slow growing tumours are well circumscribed , firm , round or multinodular lesion partly or fully encapsulated by pseudocapsule.

Cystic changes may be prominent.

Rapidly growing tumours are poorly circumscribed with a variegated , friable appearance.

There may be areas of haemorrhage and necrosis with cyst formation.

Microscopic features:

The two main variants are the monophasic and the biphasic types.

In both variants there are spindle shaped cells set in a collagenous backround.

I.  Biphasic pattern of synovial sarcoma consists of an admixture of glandular structures lined by cuboidal or columnar epithelium set in a sarcomatous stroma.

In some occult cases clusters of plump cells with pale cytoplasm are present in a spindle cell stroma.

These nests of cells are accentuated by reticulin stain.

II.  Monophasic pattern of synovial sarcoma is characterized by monomorphic population of spindle shaped cells arranged in fascicles.

The cells contain uniform tapering nuclei and pale cytoplasm.

Mitotic figures are present in variable numbers.

Other striking features include:

- Presence of mast cells

- Calcification with or without ossification. Calcification is usually preceded by hyalinization.

This is an important microscopic finding.

Prognosis is better for synovial sarcoma associated with osseous metaplasia or extensive calcification.

- Hemangiopericytoma - like vascular pattern.

III.  Monophasic epithelial variant of synovial sarcoma (extremely rare).

IV.  Poorly differentiated (PD) variant of synovial sarcoma. 

3 main groups :

- Round cell morphology associated with necrosis and high mitotic count.
(Differential diagnosis includes 'round cell tumours' -
Ewing's sarcoma / PNET , alveolar rhabdomyosarcoma, desmoplastic round cell tumours, Merkel cell tumours).

- Polygonal larger cells which sometimes show rhabdoid morphology.
(Differential Diagnosis -
Epithelioid sarcoma, undifferentiated carcinoma )

-  High grade spindle cell tumour with 'herringbone" growth pattern
(Differential Diagnosis - Malignant peripheral nerve sheath tumour
, fibrosarcoma)

Synovial sarcomas are also described in the pleural cavity where they may be confused with both mixed and sarcomatoid variants of mesothelioma.

A diagnosis of synovial sarcoma should be considered particularly if an abdominal spindle cell neoplasm shows a haemangiopericytomatous pattern and diffuse CD99 and CD56 immunopositivity.

A confident distinction between abdominal synovial sarcoma and GIST requires KIT/PDGFRA mutation analyses and specific molecular testing for synovial sarcoma

Synovial sarcoma demonstrates nuclear staining with TLE1 (transducin-like enhancer of split-1)

Distinction between poorly differentiated variant of Synovial sarcoma and Ewing's sarcoma/PNET:

FLI-1 has been described to be a useful marker for Ewing sarcoma


            Poorly differentiated synovial sarcoma                                              PNET/Ewing's sarcoma

FLI-1                   Negative                                                                                             Positive

TLE1                     95% cases positive                                                                         Negative

CD99               Cytoplasmic staining present.                                                            Shows strong              
     Membranous pattern of staining absent.                                                 membranous staining

60% cases positive                                                                         Focally positive

CK19                      Positive                                                                                            May be positive

CK7                         Positive                                                                                            Negative


Low and high power images of poorly differentiated variant of synovial sarcoma.

Poorly differentiated variant of synovial sarcoma is a round cell sarcoma which may be histologically indistinguishable from Ewing's Sarcoma / PNET.

The diagnosis of synovial sarcoma was established by :

Cytogenetic analysis:   Detection chromosomal rearrangement of SS18

Further reading:

Poorly differentiated synovial sarcoma: Immunohistochemical distinction from primitive neuroectodermal tumors and high-grade malignant peripheral nerve sheath tumors.  

Utility of cytokeratin subsets for distinguishing poorly differentiated synovial sarcoma from peripheral neuroectodermal tumour. 

Synovial sarcoma histologically mimicking primitive neuroectodermal tumour/Ewing's sarcoma at distant site.

Should molecular testing be required for diagnosing synovial sarcoma ? A prospective study of 204 cases 

Identification of poorly differentiated synovial sarcoma : a comparison of clinicopathological and cytogenetic features with those of typical synovial sarcoma. 

Special stains:

Histochemistry- Secretions within the epithelial cells and pseudoglandular spaces are PAS positive and diastase resistant, alcian blue and mucicarmine positive.

The stromal mucin secreted by the spindle cells are alcian blue positive but PAS negative.

Reticulin stain demonstrate the biphasic pattern of the tumor. Nests of plump rounded cells are highlighted by the reticulin stain.


Synovial sarcoma demonstrates nuclear staining with TLE1 (transducin-like enhancer of split-1) in 95% of tumors and appears to be a very sensitive marker. TLE1 encodes for a transcriptional corepressor that is involved in epithelial and neuronal differentiation.

In Synovial sarcoma there is usually coexpression of mesenchymal (vimentin) and epithelial markers (cytokeratin and EMA).

The following immunomarkers are useful in the diagnosis:

  -  Cytokeratin (+)

Only synovial sarcoma is positive with  cytokeratins 7 and 19 , other soft tissue sarcomas including synovial sarcoma is  positive with cytokeratin 8 and 18 ;

In monophasic synovial sarcoma immunoreactivity of cytokeratin is reduced by almost 60% ;

    - Cytokeratin positivity is noted in only 50% cases of PD synovial sarcoma.

   - EMA (+) (more sensitive than cytokeratin) ,

   - S100 protein (+) in some cases,

   - CD99 (+) in 2/3rd of cases .

CD99 (positive)

   - bcl-2  (+) in most cases.

Application of a panel of immunohistochemical markers is suggested to avoid diagnostic pitfalls.

Diagnostic clue:  In the differential diagnosis of  'round cell tumours expressing epithelial markers' , poorly differentiated synovial sarcoma should be included .


As one of the first sarcomas to be defined by the presence of a specific chromosomal translocation leading to the production of the SS18-SSX fusion oncogene, it is perhaps a typical "translocation-associated sarcoma," and its translocation remains unique to this tumor type.

Differential diagnosis: Malignant peripheral nerve sheath tumor; Solitary fibrous tumor ; Abdominal spindle cell neoplasm (GIST) depending on the site of the lesion

The following factors indicate poor prognosis-

- More than 5 cm size ;

- Presence of neurovascular invasion ;

- Lower extremity tumour location ;

- Grade 3 nuclei ;

- Presence of rhabdoid cells ;

- More than 10 mitosis/ 10 HPF. ;

- Atleast 20% of tumour shows poorly differentiated areas. ;

- Overexpression of p53 ;

- High Ki-67 proliferation index.


Further reading:

Circulating tumor cells in sarcomas: a brief review.

Synovial Sarcoma: Recent Discoveries as a Roadmap to New Avenues for Therapy.

Right ventricle inflow obstructing mass proven to be a synovial sarcoma

Synovial sarcoma in children and adolescents.

Synovial sarcoma: defining features and diagnostic evolution.

Primary Synovial Sarcomas of the Mediastinum: A Clinicopathologic, Immunohistochemical, and Ultrastructural Study of 15 Cases.  

Primary pulmonary synovial sarcoma confirmed by molecular detection of SYT-SSX1 fusion gene transcripts: a case report and review of the literature.

Prognostic significance of histologic grade and nuclear expression of beta-catenin in synovial sarcoma. 

Matrix metalloproteinase-2 expression correlates with morphological and immunohistochemical epithelial characteristics in synovial sarcoma.




Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)






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