The significance of sarcomatoid and rhabdoid dedifferentiation in renal cell carcinoma

•Sarcomatoid and/or rhabdoid dedifferentiation are infrequent events that may be heterogeneous throughout a given renal cell carcinoma (RCC) tumor and confer a poor prognosis.•Sarcomatoid dedifferentiation is thought to arise from a common cell of origin with the epithelial component of an RCC, but the sarcomatoid component has a higher incidence of alterations in TP53, CDKN2A, and the Hippo pathway. Rhabdoid dedifferentiation also exhibits clonal evolution and TP53 alterations, yet gene expression is similar across the rhabdoid and epithelial components and distinct from clear cell RCC.•Sarcomatoid dedifferentiation has shown remarkable responses to immune checkpoint therapy combinations, particularly nivolumab plus ipilimumab, whereas less is known about outcomes with systemic treatment for rhabdoid dedifferentiation. Dedifferentiation in renal cell carcinoma (RCC), either sarcomatoid or rhabdoid, is an infrequent event that may occur heterogeneously in the setting of any RCC histology and is associated with poor outcomes. Sarcomatoid dedifferentiation is associated with inferior survival with angiogenesis targeted therapy and infrequent responses to cytotoxic chemotherapy. However, immune checkpoint therapy has significantly improved outcomes for patients with sarcomatoid dedifferentiation. Biologically, sarcomatoid dedifferentiation has increased programmed death-ligand 1 (PD-L1) expression and an inflamed tumor microenvironment, in addition to other distinct molecular alterations. Less is known about rhabdoid dedifferentiation from either a clinical, biological, or therapeutic perspective. In this focused review, we will discuss the prognostic implications, outcomes with systemic therapy, and underlying biology in RCC with either sarcomatoid or rhabdoid dedifferentiation present.