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Synovial Sarcoma Dr. Prabesh Kr. Choudhary 2nd Year Resident, Pathology: 

Synovial Sarcoma Dr. Prabesh Kr. Choudhary 2 nd Year Resident, Pathology

What is Synovial Sarcoma?: 

What is Synovial Sarcoma? Synovial sarcoma (SS) is a mesenchymal spindle cell tumour which displays variable epithelial differentiation, including glandular formation and has a specific chromosomal translocation t(X;18) (p11;q11).

Epidemiology: 

Epidemiology Accounts for 5 to 10% of the soft tissue sarcomas. Has been reported from birth to 89 years but more common in young adults. Males affected more than females. 90% cases occur before 50, and most common in between 15 and 35 years. Approximately 800 new cases occur per year in the United States.

Sites of Involvement: 

Sites of Involvement Over 80% arise in deep soft tissue of extremities, especially around the knee and adjacent to joint or tendon sheaths. Around 5% arises in head and neck region. Unusual sites:

Unusual Sites of Occurence: 

Unusual Sites of Occurence Head and Neck · Orofacial · Tongue · Tonsil · Larynx · Trachea · Parapharynx Abdominal wall Vulva Penis Kidney Prostate Skin Intravascular

Unusual Sites of Occurrence;contd: 

Unusual Sites of Occurrence;contd Intra-abdominal · Mesentry · Retroperitoneum Intrathoracic · Mediastinum · Pleura · Lung · Heart · Oesophagus Intraneural Intra-osseous Intra- articular Intracranial · 3 rd ventricle

Symptoms: 

Symptoms The most common presentation is a swelling or mass with or without pain or tenderness. Pain or tenderness can be present for several years even though a mass could not be felt. Local symptoms e.g. dysphagia . Growth is often slow, averaging 2-4 yrs, and 20 yrs-histories are known.

Etiology: 

Etiology No specific predisposing factors. Occurrence has been associated with metal implant used in hip replacement, and radiotherapy in Hodgkin disease. Specific chromosomal translocation that is presumably relevant in pathogenesis has been found.

Diagnostic Methods: 

Diagnostic Methods The most effective way to diagnose this cancer is by having a tissue biopsy. Magnetic Resonance Imaging (MRI) is very useful in determining the extent to which the cancer has grown. Computed Tomography (CT) Scan.

Imaging findings: : 

Imaging findings: Soft tissue mass of moderate density in close proximity to a joint. Occasional bone invasion(15 to 20%). May cause a periosteal reaction. Multiple spotty calcifications(15 to 20%). Metastases to lungs and bone.

Macroscopy: 

Macroscopy Usually 3-10cm in diametre and circumscribed. Tan or grey, and soft when lacking fibrous stroma . Frequently multinodular , and can be multicystic . Necrosis is seen in poorly differentiated (PD) SS.

· Histopathology: 

· Histopathology Histologically 3 types: Biphasic SS: Both epithelial and spindle cell components. Monophasic SS: · Spindle cell · purely glandular · Epithelial cell Poorly differentiated

Monophasic SS: 

Monophasic SS

Biphasic SS: 

Biphasic SS

Poorly Differentiated SS: 

Poorly Differentiated SS

D/D of Synovial Sarcoma: 

D/D of Synovial Sarcoma Fibrosarcoma MPNST Adenocarcinoma Mesothelioma Small round cell tumors

Immunophenotyping: 

Immunophenotyping Cytokeratin (CK): · 90% of SS express CK (7 and 19) in · epithelial component. Epithelial membrane antigen(EMA): Use of both CK and EMA. Others: S 100(30%); CD99(62%);BCL2 Muscle marker: Calponin , desmin , actin Vimentin

Immunophenotyping; Contd.: 

Immunophenotyping ; Contd. Immunophenotyping in Monophasic SS: Role of immunophenotyping in the differential diagnosis of synovial sarcoma.

Cytogenetics: 

Cytogenetics t(X;18)(p11;q11) is the cytogenetic hallmark of SS, being present in more than 90% of the cases. Other cytogenetic abnormalities: -3, +7, +8, and +12.

Molecular Genetics: 

Molecular Genetics Genes affected by t(X;18): · Chromosome 18: SS18(SYT or SSXT) · X-chromosome: SSX1, SSX2, and SSX4 FISH and RT-PCR can be used as rapid diagnostic tools. SS18 gene: 418 Amino acids; transcriptional coactivator ; embryogenesis. SSX gene (5 members): 188 amino acid protein; transcriptional repressor.

Molecular Genetics; contd.: 

Molecular Genetics; contd. In most SS18/SSX fusion proteins identified, the C-terminal 8 amino acids of SS18 are replaced the last 78 amino acids of SSX augmenting the transcriptional co activating activity. SS18/SSX2 fusion more common in biphasic SS. SS18/SSX1 fusion more common in monophasic SS.

Histogenesis: 

Histogenesis Very controversial issue. Why ‘Synovial’? Sarcoma or Carcinoma? Normal or reactive synovial cells do not express keratin. Epithelial rest or mesenchymal tissue with epithelial metaplasia .

Treatments: 

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

Surgery: 

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 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 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.

prognosis: 

prognosis 50% of SS recur, usually within 2 yrs, but sometimes up to 30 yrs after diagnosis. 40% cases metastasize, commonly to lungs and bones and also in regional lymph nodes. Adequate local excision with postoperative radiotherapy can control local recurrence. 5 yrs survival is 36-76% and 10 yrs survival is 20-63%.

Prognosis; contd,: 

Prognosis; contd , Survival has been increased by adjuvant therapy. Best outcomes have been found in following circumstances: · Childhood patients. · Tumor less than 5cm in diameter. · Less than 10 mitosis/10 hpf . · No necrosis. · Tumor eradicated locally.

Prognosis; contd,: 

Prognosis; contd , Other prognostic factors: Site: Extent of calcification: Rhabdoid cell: Mast cell count: Proliferative index: Ploidy :

Prognosis; contd,: 

Prognosis; contd , Prognosis does not differ between monophasic and biphasic tumors or in relation to immunophenotyping . Cases with SS18/SSX2 fusion which is mostly found in MSS, have a better prognosis. PDSS is very aggressive and metastasize in high percentage of cases. Calcifying variant has better prognosis.

Questions?: 

Questions?