Pathology of Clear Cell Sarcoma 

Dr Sampurna Roy MD                2022

Clear cell sarcoma is a rare aggressive, soft tissue sarcoma which was initially named "malignant melanoma of soft parts".These tumors share histological and immunohistochemical characteristics with malignant melanoma.  Unlike malignant melanoma however, most clear cell sarcomas are associated with a t(12;22)(q13-14;q12) translocation.

It was originally described by Enzinger et al in 1965.

Clear cell sarcoma stain positive for the melanocyte immunohistochemical markers HMB-45 and S-100. It is thought to derive from neural crest cells. These markers are useful for distinguishing clear cell sarcoma from epithelial tumours and synovial sarcomas.

It is a slow growing, progressive tumour with poor prognosis.

The tumour is commonly arise from tendinous sheaths and aponeuroses, with the majority located in the extremities, specially around the knee, feet and ankle. Some cases have been described as arising in the chest wall and scapular soft tissues.

The patients are mostly young adults between the ages of 20 and 40 years with a higher incidence in female.

Grossly, the tumour is firm well circumscribed grey or white in appearance.

Poor prognosis is indicated by large size of the tumour , presence of necrosis and local recurrence.

Tumors <5 cm are much less likely to recur or metastasize, whereas those >5 cm are more commonly associated with metastatic disease.

Focal or diffuse tumor necrosis also correlates with a worse prognosis, independent of tumor size.

Metastasis occurs in more than 50% cases. Lymph node metastasis is  associated with a poor prognosis, since patients with regional metastasis eventually will develop distant metastasis.

Common sites of metastasis include bone, lymphnode and lungs. Repeated local recurrence is common in clear cell sarcoma.

The characteristic translocation t (12 ; 22) (q13 ; q12)  results in a fusion gene EWS/ATF1.  

The EWS/ATF1 fusion transcript is detectable in almost 90% of cases.

 Differential diagnosis of clear cell sarcoma:

1. Malignant melanoma (mitotic activity, cellular atypia and nuclear pleomorphism more prominent in melanoma)

Immunohistochemical studies in clear cell sarcoma commonly show neoplastic cells positive with HMB-45, S100 protein, and Melan-A. Most cases exhibit a t(12;22)(q13;q12) translocation causing an EWSR1/ATF1 gene fusion, a finding that helps differentiate these lesions from malignant melanoma.

2. PEComas- Clear cell myomelanocytic tumour - Clear cell myomelanocytic tumor belongs to a family of tumors known as perivascular epithelioid cell family of tumors, which present commonly in the abdomen, usually in the ligamentum teres of the liver of young patients.                                                 

3. Malignant peripheral nerve sheath tumour  - Usually arises within large peripheral nerves and is negative for HMB-45.

4. Melanotic Schwannoma,

5. Cellular Blue Naevus

6. Synovial Sarcoma (monophasic type) - Synovial sarcoma commonly shows a t(X;18)(p11.2;q11.2) translocation producing SYT/SSX1 or SYT/sSSX2 gene fusions, not seen in clear cell sarcoma.

7. Alveolar Soft Part Sarcoma

8. Epithelioid Sarcoma