Clear Cell Sarcoma of the Knee: A Case Report of Diagnostic Challenges, Rapid Metastatic Spread, and Treatment Dilemmas

Clear cell sarcoma (CCS) is a rare, aggressive soft tissue sarcoma with a strong predilection for the extremities. It is often misdiagnosed as melanoma. Despite surgical resection, CCS carries a high risk of early metastasis, most commonly to the lungs, bones, and lymph nodes, with limited effective systemic therapies available. We present the case of a 48-year-old man with CCS of the knee, initially presenting as a localized disease but rapidly progressing to widespread metastasis within three months. The patient underwent radical resection with knee arthroplasty and adjuvant radiotherapy, followed by systemic therapy with cabozantinib, ipilimumab, and nivolumab. Despite aggressive treatment, the disease progressed, leading to recurrent pleural effusions, respiratory failure, and, ultimately, the patient's demise within 10 months of diagnosis. This case underscores the highly aggressive nature of CCS and the challenges associated with its management. The rapid metastatic spread despite multimodal therapy highlights the need for improved early detection strategies and more effective systemic treatments, including novel targeted therapies and immunotherapy combinations.