SYNOVIAL SARCOMA

DR NARMADA PRASAD TIWARI

What is Synovial Sarcoma?

The name "synovial sarcoma" was coined early in the 20th century, as some researchers thought that the microscopic similarity of some tumors to synovial, and its propensity to arise adjacent to joints, indicated a synovial origin; however, the actual cells from which the tumour develops are unknown and not necessarily synovial.

Synovial sarcoma is a misnomer because this malignancy is only rarely found within joints and it has no immunocytochemical relationship to the CK-negative normal synovium

What is Synovial Sarcoma?

This is a rare and aggressive soft tissue malignant tumor that begins near joints in the body.

Site-Typically around ankle and knee joint.Around shoulder and hip joint.Other site- including neck (particularly the retropharyngeal

area), anterior abdominal wall, abdominal cavity, retroperitoneum, mediastinum , blood vessels, nerves.

Lately, it has become evident that the distribution of this tumor is even wider, with cases reported in the oral cavity salivary glands, lung, gastrointestinal tract , kidney, prostate and vulva.

Who is Affected?

Age- 30 yr.

Male: Female- 1.2

Etiology

The exact etiology of Synovial sarcomas is unknown.

What is known is that many Synovial sarcoma cells are characterized by a chromosomal translocation that fuses the SYT gene from chromosome 18 to either the SSX1 or the SSX2 gene.

Etiology Continued

The fusion proteins SYT-SSX1 and SYT-SSX2 are believed to function as abnormal transcriptional regulators that result in

Either activation of proto-oncogenes or inhibition of tumor suppressor genes.

Break-apart FISH probes can reliably identify the SYT disruption in synovial sarcoma. Two probes, one in the red and one in the green spectrum stain the 18q11.2 region. The normal and abnormal (broken apart) one can be seen here

Symptoms

The most common symptom experienced is a swelling or mass that may be accompanied by pain or tenderness.

In a few cases it has been noted that pain or tenderness was present for several years even though a mass could not be felt.

Limping or difficulty using legs, arms, hands or feet have been reported.

GROSS

well-circumscribed, firm, and grayish pink. Focal calcification is frequent and may be detected radiographically.When located in the hands or feet, it may have extremely small dimensions.

MICROSCOPY

Biphasic tumor composed of sharply segregated epithelial and sarcomatous components

The epithelial areas usually appear in the form of gland-like spaces lined by cuboidal or columnar cells, but can also present as solid nests of large pale cells. It is exceptional for this component to exhibit squamous features.[1537]

The sarcomatous component is made up of spindle cells with a fibroblast-like appearance.

It tends to be hypercellular but with a relatively monotonous appearance, plump nuclei, a focally whorled pattern, distinct lobulation or fasciculation,,

Large number of mast cells

Hyalinization,

calcification, and When the calcification is particularly heavy, the term calcifying synovial sarcoma has been used.

osseous metaplasia can be present.

Typical biphasic appearance of synovial sarcoma

Calcifying synovial sarcoma. , Radiographic appearance of tumor located in popliteal space

Calcifying synovial sarcoma.. Microscopic appearance.

Monophasic synovial sarcoma is composed of only one of the two components.

In the large majority of cases, this applies to the spindle cell sarcomatous component, which is easily misdiagnosed as fibrosarcoma,hemangiopericytoma.

A search for epithelial-looking foci should be carried out in these situations, as well as a thorough immunohistochemical (and possibly molecular) evaluation

Theoretically, a monophasic form of synovial sarcoma composed only of the epithelial elements of the tumor should also exist.

The fact that in some neoplasms the glandular elements are so prominent as to simulate a metastatic adenocarcinoma cannot be denied.

However, the existence of a pure form of monophasic epithelial synovial sarcoma has yet to be convincingly demonstrated at the cytogenetic/molecular level

A poorly differentiated form of synovial sarcoma is being increasingly recognized, characterized by a greater degree of cellularity, atypia, and mitotic activity.

The tumor cells may be spindle, small, or large and clear, Here too, immunohistochemical and particularly cytogenetic/molecular confirmation becomes crucial

Monophasic synovial sarcoma. The tumor is hypercellular but remarkably monomorphic

Differential diagnosis

Fibrosarcoma.AdenocarcinomaMesothelioma (WT-1)Small round cell tumour.

SPECIAL STAIN

Special stains: Histochemistry- Secretions within the epithelial cell 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 ;

   - EMA (+) ,    - Vimentin (+),

in some cases S100 protein (+), CD99 (+) .

   - bcl-2  (+)

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

epithelial membrane antigen (EMA) positivity is found near the periphery of the lesion. Up to 97% of cases of synovial sarcoma will have EMA+ areas.

CD99, the product of the MIC2 gene is seen in a membranous pattern and can be detected in up to 70% of synovial sarcomas

, the bcl-2 protein can be demonstrated strongly, as here. These immunohistochemistry stains help confirm the diagnosis of synovial sarcoma.

Cytogenetics

Synovial sarcoma is associated with chromosomal translocation t(x ;18) (p11.2 ; q11.2).

Synovial sarcoma can recur locally .

Metastasize distantly, particularly to the lung and lymph nodes.

The incidence of nodal metastases is in the range of 10–15%

Prognosis

Better for the synovial sarcomas associated with heavy calcification (calcifying synovial sarcoma),

Age (better in young patients),

Site (better for distal lesions),

SIZE-better for tumors less than 5 cm in diameter),

Status of the surgical margins,

Mitotic activity (better for tumors having fewer than 15 mitoses per 10 high-power fields),

Necrosis (worse for tumors having tumor necrosis of more than 50%),

Rhabdoid cells (worse when present),

Dysadherin expression (worse when present, indicating E-cadherin dysfunction),

DNA ploidy pattern (worse for aneuploid tumors).[

Treatments

Synovial sarcomas may be treated by using the following medical approaches… Surgery Radiation Chemotherapy

Surgery

Complete surgical excision of the tumor, nearby muscle and lymph nodes is the best way of treating this cancer.

Depending on the location and size of the tumor, it may be necessary to remove all or part of a limb.

Radiation

Radiation is often used in conjunction with surgery to kill cancer cells.

It can be given before surgery in order to shrink a tumor or afterwards to kill any remaining cancer cells.

On rare occasions radiation alone has been used for treatment of the primary tumor.

Chemotherapy

Chemotherapy has been proven highly effective with treating this form of cancer and it may be administered in one of the following ways… As a pill to swallow As an injection into the muscle or fat tissue Intravenously is the most common form of delivery for

chemotherapy drugs.

REGULAR CALCIFIED

Average age- 30Sex-(m:f)- 1.2 Site-Extremities Recurrance-32- 55%Metastatis-52-74%Survival- 5 yr- 50%

261.9Extremities 32%25%83%

SYNOVIAL SARCOMA

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