Answer: B

Histological Description: Arising from the renal pelvis is a low grade papillary urothelial carcinoma with minimal cytological atypia. In addition, there is a proliferation of irregular nests in the hilar peri-pelvic adipose tissue. The nests are associated with a desmoplastic stromal reaction. Cytologically, the tumor within the nests are very bland with virtually no atypia and no mitotic figures.

Discussion: Florid von Brunn nest (VBN) proliferations are very common in the ureter and renal pelvis. At cystoscopy, VBN proliferations can be tumor-like presenting as a polypoid mass with a smooth surface.  These are usually < 3 cm., but can have a wide range in size. At low magnification, the surface is smooth without exophytic papillary fronds. The lamina propria is filled with evenly small rounded uniform nests. In resection specimens, one can appreciate that the nests are linear or lobular without an infiltrative lower border (i.e. can mentally draw a straight line at the base of the lesion).  There is no associated stromal reaction. Most cases have a low ki67 rate.

With an inverted component of noninvasive low grade papillary urothelial carcinoma, the vast majority of papillary urothelial neoplasms have some exophytic component, although uncommonly the entire lesion is inverted. The lamina propria filled with large rounded nests of urothelium which lack an infiltrative border at the base of the lesion and would not extend into renal hilar adipose tissue. The nests are crowded with a more uniform spacing than nested carcinoma. There is lack of desmoplastic stroma. Ki67 can be low although typically higher than proliferation of VBN.

Nested urothelial carcinoma typically occur in the bladder, with only rare cases in the renal pelvis or ureter. At cystoscopy, there is a nodular surface typically without an exophytic papillary component with a wide range in size. At low magnification, the surface is typically smooth without exophytic papillary fronds, although uncommonly, as in the current case, the surface shows CIS or papillary urothelial carcinoma. The lamina propria is filled with small crowded nests of urothelium in the classic variant and large irregular nests in the large nested variant. As in the current case, there is an irregular base with infiltrative nests extending to different depths. In the current example, the nests are in adipose tissue in the renal hilum that is diagnostic of invasive carcinoma. Typically, there is no stromal reaction in the usual nested variant but a variable desmoplastic stroma with variable inflammatory response can be seen in the large nested variant. The diagnosis of nested urothelial carcinoma should not be made on biopsy of the ureter or renal pelvis in the absence of muscularis propria invasion, since on biopsy one cannot appreciate an infiltrative border and given the overlapping morphological features with von Brunn nests in these sites. Most cases have a low ki67 rate, with only a few cases with a rate >20%. Nested carcinoma has an  aggressive behavior comparable to invasive high grade urothelial carcinoma.