Papillary RCC (renal cell carcinoma) represents between 7% and 15% of all RCCs. 1 Some cases of papillary RCC are hereditary, and these have been associated with germline mutations of the c-MET oncogene. 1,2,3 Male patients predominate with a male to female ratio of approximately 1.8-4:1. 3 Ages range from early adulthood to old age and peak in the 6th to 7th decades. Large papillary RCC can be cystic and necrotic. More than 50% of the papillary RCC are diagnosed as incidental masses on imaging studies. Contrast-enhanced imaging studies usually reveal an avascular or hypovascular lesion, in contrast to clear cell RCCs, which are often hypervascular. 4,5 Patients with a low-grade and low-stage papillary RCC have an excellent prognosis, whereas those with high-grade or high-stage papillary RCC typically have poor outcomes. 3 Low-grade papillary RCCs are often small peripheral tumors and are amenable to partial nephrectomy. Despite the high rate of multi-focality, patients do not appear to be at increased risk for local recurrence after partial nephrectomy. Papillary RCCs have a mortality of at least 16% at 10 years and sometimes manifest with metastases. 4,5

Papillary RCCs are further divided into two basic morphologic subtypes, types 1 and 2, which correlate with tumor grade. 1,2,4,5 Type 1 papillary RCC, the more common type, is a low-grade tumor composed of papillae that are lined by a single layer of tumor cells with scanty pale cytoplasm. Nuclei are small, round, and grooved with inconspicuous nucleoli (Fuhrman grade 1 or 2). Type 2 papillary RCC is less common and is a high-grade tumor composed of papillae lined by larger, eosinophilic and often pseudostratified tumor cells. The nuclei in type 2 tumors are large with prominent nucleoli (grade 3). 1,2,3,4 Immunohistochemically, papillary RCCs are immunoreactive for EMA, low-molecular-weight keratins, RCC, AMCAR, CD10, PAX8, PAX2 and CK7, and negative for high-molecular-weight keratin 34BE12, CD117, and WT1.6,7

Cytologically, the cells of a type 1 papillary RCC may resemble benign distal tubular cells. However, benign tubular cells are rarely present in large numbers, and never show papillae or spherule formation like in papillary RCC. Distorted benign glomeruli, with their densely cellular, spherical, and papillary arrangement, can be misinterpreted as a papillary RCC. Identifying the capillary loops on the edge is critical for recognition of glomeruli. Focal papillae and high nuclear grade in clear cell RCC may simulate type 2 papillary RCC. However, hallmarks of clear cell RCC include the presence of intricate blood vessels, abundant vacuolated or clear cytoplasm, a lack of foamy macrophages and intracytoplasmic hemosiderin, and negative immunohistochemical stain for CK7 and AMACR. 1,2 The diagnosis of papillary RCC in a young person should be made only after epithelial-predominant Wilms’ tumor has been excluded due to morphologic similarities between the two tumors. 8 Other  differential diagnoses include papillary hyperplasia within renal cysts, papillary urothelial carcinoma, chromophobe RCC, collecting duct carcinoma, and translocation-associated RCC.1