Background: Clear cell sarcoma (CCS) is a rare soft tissue sarcoma primarily affecting lower extremities. Although CCS shares similarity with malignant melanoma, it’s often associated with EWS and ATF1 fusion genes that is not observed in melanoma.
Case presentation: We report a case of a young female presented with a malignant tumor in the perineum. She underwent local tumor resection and was initially diagnosed with malignant melanoma. Tumor reoccurred just after 4 months postoperation. Further genetic testing revealed an EWSR1-AT gene rearrangement, leading to the revised diagnosis of clear cell sarcoma originating from the vulva. The patient received anlotinib as the first-line therapy and envafolimab combining with Lenvatinib as the second-line. The patient experienced subjective relief and achieved a PFS of 3 months with both treatment regimens. After disease progression, chemotherapy as the third-line, and cabozantinib as the fourth-line therapy provided minimal clinical benefit. The patient had an overall survival of 22 months.
Conclusion: Between CCS and malignant melanoma, differential diagnosis is exceedingly important by molecular genetics tests. Our observations suggest that target therapy combined with immunotherapy may be a promising treatment option for locally advanced or metastatic CCS.