Answer: Nested variant of urothelial carcinoma

Histology: Large irregular nests of urothelium extend deep into the muscularis propria and focally into the perivesicular soft tissue. Cytologically, the urothelial cells are extremely bland, some with nuclear grooves as seen in normal urothelium, and virtually no mitotic activity. In general, there is little to no stromal reaction around the tumor nests. On the surface there is a focal exophytic papillary component.

Discussion: There is a general rule in bladder pathology that if you see nests of urothelium in the muscularis propria then it has to be invasive urothelial carcinoma. Mimickers of invasive urothelial carcinoma, such a florid proliferation of von Brun nests or inverted papilloma can be large and fill the lamina propria but not extend into the muscularis propria. The only exceptions are non-tumoral, such as in a diverticulum, urachal remnant, and the intramural portion of the ureters. Similarly, inverted growth patterns of PUNLMP or non-invasive low grade papillary urothelial carcinoma do not invade the muscularis propria. The findings in this case are typical of nested urothelial carcinoma, and in particular the large nested variant. The hallmark of nested carcinoma is the bland cytology indistinguishable in most areas of the tumor from normal urothelium. Architecturally, typical nested carcinoma consists of small nests that are too crowded or infiltrate irregularly in the lamina propria to be von Brun nests. When nested carcinoma is seen in the muscularis propria, the diagnosis is more straightforward since as noted above von Brun nests do not extend into the muscularis propria. The large nested variant consists of much larger nests that mimic the inverted growth pattern on non-invasive PUNLMP or low grade papillary urothelial carcinoma. However, if nests of urothelium are seen infiltrating between bundles of the muscularis propria no matter how cytologically bland, then the diagnosis is nested carcinoma. It is very difficult to diagnose large nested carcinoma on a biopsy where muscularis propria invasion is not seen. In these cases the irregular and haphazard arrangement of the nests provide the clues to its malignancy. In most cases of nested carcinoma there is no surface precursor component which adds to the difficulty in establishing a diagnosis. Nested carcinoma, stage for stage, behaves the same as infiltrating high grade urothelial carcinoma.

References:

Large nested variant of urothelial carcinoma: 23 cases mimicking von Brunn nests and inverted growth pattern of noninvasive papillary urothelial carcinoma. Cox R, Epstein JI. Am J Surg Pathol. 2011 Sep;35(9):1337-42.

Florid von Brunn nests mimicking urothelial carcinoma: a morphologic and immunohistochemical comparison to the nested variant of urothelial carcinoma. Volmar KE, Chan TY, De Marzo AM, Epstein JI. Am J Surg Pathol. 2003 Sep;27(9):1243-52.