Clear Cell Sarcoma

Abstract

Clear cell sarcoma (CCS) is an aggressive, rare soft-tissue sarcoma, initially described by Dr. Enzinger. The tumor has a propensity to involve the tendons and aponeuroses of distal extremities of relatively young individuals. This sarcoma is characterized by multiple local recurrences with late metastases, frequent lymph node involvement and a poor prognosis. CCS is also referred as a malignant melanoma of soft parts because of its melanocytic features. Molecular genetic studies have shown cytogenetic rearrangements resulting in a EWSR1-ATF1 fusion gene specific of CCS. Poor prognostic factors include mitotic index ≥10, presence of necrosis, primary tumor size ≥5 cm, presence of metastases at diagnosis and trunk localization. Wide surgical excision remains the only curative treatment for localized cases. Sentinel node biopsy has been reported in CCS but the benefit of this procedure still needs further investigation. The treatment of advanced, inoperable CCS remains indeed a challenge due to the lack of an established systemic standard of treatment. CCS tends to be resistant both to chemotherapy and to radiation therapy. Objective tumor responses have been observed upon tyrosine kinase inhibitors (sorafenib and sunitinib). A recent phase II trial demonstrated that crizotinib provided a clinical benefit, with 69.2% of CCS cases achieving disease control for a median of 131 days. Anecdotal reports have included a complete response to interferon alpha, stable disease for 6–24 months in two patients after ipilimumab treatment, and a partial and a complete clinical response in two patients after pembrolizumab.