Papillary renal epithelial tumors can be either benign or malignant.  Papillary adenoma (PA) is a benign lesion which is morphologically similar to papillary renal cell carcinoma (PRCC) but is unencapsulated and typically smaller in size (less than 1.5 cm).  There is some evidence to suggest that PAs are a precursor to PRCC as both tumor types can share a KMT2C-specific mutation. ¹ Both PA and PRCC are also frequently seen in end-stage kidney disease.  PRCC has been shown to demonstrate chromosomes 7 and 17 gains; acquiring additionally polysomies represents the progression of low to high tumor grade.  Some tumors with papillary architecture and high-grade eosinophilic cytology (previously classified as “type 2 PRCC”), are now known to represent a heterogeneous group of tumors which includes PRCC, but also includes other previously unrecognized, but distinctive types of renal cell carcinomas characterized by distinct molecular findings (e.g., FH-deficient RCC), and already incorporated in the renal tumor WHO 2022 classification. ^2,3
In addition, new entities with overlapping morphologic and genetic feature to PRCC are emerging (e.g. Biphasic squamoid alveolar RCC and Warthin-like PRCC) as well as tumors with overlapping morphologic yet distinct molecular features (e.g., Biphasic hyalinizing psammomatous RCC and papillary renal neoplasms with reversed polarity) have been described. ^3-5