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).

            Visit: Primary Monophasic Synovial Sarcoma of the Lung

This tumour is commonly located in the paraarticular regions, close to tendon sheaths, bursae and joint capsules. The tumour rarely involves synovial membrane.  

Site: These are usually  located  around knee and ankle joint,as well as around hip, shoulder & elbow. Rare variants occur in the oral cavity, anterior abdominal wall, larynx, pleura, lung, pericardium, heart & mediastinum.

Gross appearance:  Gross Image
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 & 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 -PubMed Link
3 main groups : PubMed Link
 - 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.
      (D/D- Epitheliod sarcoma, undifferentiated carcinoma )
 -  High grade spindle cell tumour with 'herringbone" growth pattern
      (D/D- 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.

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

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.

Immunohistochemistry:
In Synovial sarcoma there is usually coexpression of mesenchymal (vimentin) and epithelial markers (cytokeratin & EMA).
The following immuno markers are useful in the diagnosis:
   -  Cytokeratin (+)
Only synovial sarcoma is positive with  cytokeratins 7 & 19 , other soft tissue sarcomas incl. synovial sarcoma is  positive with cytokeratin 8 & 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) ,
   - Vimentin (+), S100 protein (+) in some cases, CD99 (+) in 2/3rd of cases .
   - 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 .

Cytogenetics:
Synovial sarcoma is associated with chromosomal translocation t(x ;18) (p11.2 ; q11.2).
SSX  gene in chromosomeX and SYT gene in chromosome18 are involved.

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.