Abstract
Non-clear cell renal cell carcinoma (RCC) is a heterogeneous disease. We report a case of sarcomatoid non-clear cell RCC in a patient with underlying multiple sclerosis (MS) on immunosuppression with a complete pathologic response to pembrolizumab and axitinib. Comprehensive genomic profiling revealed pathogenic mutations in SETD2 and TP53 with high RNA expression levels of immune checkpoint proteins. Our case illustrates the importance of treatment selection based on presence of sarcomatoid features, underlying autoimmune disease, and genomic profiling.