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Clear cell sarcoma from diagnosis and multidisciplinary treatment to clinical trials

Anna M. Czarnecka1, Paulina Chmiel1, Paweł Sobczuk12, Mateusz Spałek3, Anna Szumera-Ciećkiewicz4, Ewa Bartnik56, Marcin Zdzienicki1, Tomasz Świtaj1, Monika Dudzisz-Śledź1, Piotr Rutkowski1

Abstract

Clear cell sarcoma (CCS), formerly called soft tissue melanoma, is a rare malignant soft tissue sarcoma (STS) characterized by a propensity for lymphatic spread and poor prognosis. Clear cell sarcoma can be distinguished by a t(12; 22) (q13; q12) translocation, which in addition to diagnostic implications may be important for targeted treatment in the future. Clear cell sarcoma occurs mainly on the extremities, most often the shin (in the feet and ankle area), in the tendons, and aponeurosis, often at a young age. Considering the significant ability to develop metastases to regional lymph nodes (about 30% of cases), a sentinel node biopsy (SLNB) should be considered in diagnosis, with possible subsequent radical lymphadenectomy (LND) in the case of metastases. Treatment of localized disease is limited to radical local excision with optional complementary radiotherapy. Due to the resistance to classical chemotherapy and the presence of characteristic molecular abnormalities, research focusing on the use of molecular targeted therapies in this group of cancers is ongoing. In clinical trials, MET inhibitors, and tyrosine kinase inhibitors (TKI) were evaluated. Clear cell sarcoma was also one of the subtypes of tumors assessed in the CREATE clinical trial with crizotinib and IMMUNOSARC with checkpoint inhibitors. However, a poor understanding of the biology and natural course of this sarcoma requires further research to develop an effective treatment and unify clinical guidelines. 

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