Sarcomatoid differentiation in RCC, recognized as a malignant spindle cell component resembling a sarcoma, is no longer thought to define a distinct subtype of RCC. Rather, it is thought to represent a common pathway of tumor dedifferentiation that can occur in any RCC subtype. Sarcomatoid differentiation in RCC has been demonstrated repeatedly to be associated with aggressive behavior independent of other pathologic parameters; patients with sarcomatoid differentiation have frequent metastases, often at the time of presentation, and short survival (median 6–19 months) [12–14]. In some studies, a higher percentage of sarcomatoid differentiation has been associated with decreased survival [12, 14]. The parent subtype of RCC does not appear to have prognostic significance once sarcomatoid differentiation has occurred [12, 13, 15], although one recent study suggests that patients with metastatic sarcomatoid carcinoma arising in association with clear cell RCC may have a better response to vascular epidermal growth factor (VEGF)-targeted therapy [16].

Grossly, areas of sarcomatoid differentiation are often seen as dense, tan to white fleshy areas with infiltrative borders, often contrasting with the softer character of the associated RCC in which they arose [12].

Microscopically, sarcomatoid differentiation is recognized as a malignant spindle cell component that resembles a sarcoma (Fig. 25.2). The appearance most commonly resembles fibrosarcoma, malignant fibrous histiocytoma, or an unclassified sarcoma. Heterologous differentiation is rare, often taking the form of osteosarcoma, chrondrosarcoma, or rhabdomyosarcoma, and has not been shown to affect outcome in the few instances reported [12, 14, 15].

Because sarcomatoid differentiation is associated with such aggressive behavior, its presence should be mentioned in the surgical pathology report. At the most recent meeting of the ISUP, there was consensus that no minimum amount of sarcomatoid differentiation was necessary to establish a diagnosis of sarcomatoid carcinoma; thus, any amount of sarcomatoid differentiation should be mentioned in the surgical pathology report [11] .

Rhabdoid differentiation, so named because it describes tumor cells that resemble rhabdomyoblasts, was described in RCC in a series by Gokden et al. in 2000 [17]. The rhabdoid phenotype is most commonly seen in association with clear cell RCC, but has been reported in numerous other subtypes, including papillary, chromophobe, medullary, and acquired cystic disease-associated RCC [18–22]. Cells with rhabdoid differentiation are variably cohesive and contain large, densely eosinophilic intracytoplasmic inclusions and eccentrically located nuclei, often with prominent nucleoli (Fig. 25.3). These hyaline inclusions do not represent muscle differentiation but rather have been shown to be aggregates of cytoskeletal filaments or degraded organelles [17, 21].

Rhabdoid differentiation has been associated with increased tumor grade and stage, as well as frequent metastasis and death of disease in several studies [17, 21, 23]. More recently, it has been shown to be independently associated with poor outcome [24]. Therefore, it should be mentioned when present. This practice was likewise supported by ISUP consensus [11].