Florid von Brunn nests mimicking urothelial carcinoma: a morphologic and immunohistochemical comparison to the nested variant of urothelial carcinoma

Abstract

Florid von Brunn nests may mimic the nested variant of urothelial carcinoma. We examined formalin-fixed, paraffin-embedded tissue from 21 cases of florid von Brunn nests and 11 cases of nested variant of urothelial carcinoma. Morphologic features were recorded in detail. Also, cases were stained with monoclonal antibodies against MIB-1, p53, p27, and cytokeratin 20. Percentage positivity was calculated by counting 300 to 500 cells from each case. Clinical follow-up information was also obtained. Florid von Brunn nests from the bladder were comprised of large nests with regular spacing, and all the nests extended to the same horizontal level at the base of the proliferation. Central lumen formation was often seen within florid von Brunn nests, at times with cystic dilatation, such that there was a spectrum from proliferating von Brunn nests to cystitis glandularis to cystitis cystica. Small, crowded nests with variable spacing and an infiltrative base characterized nested variant of urothelial carcinoma. Four cases showed detrusor muscle invasion on biopsy with an additional case showing detrusor muscle invasion at cystectomy. One additional patient with nested variant of urothelial carcinoma had distant metastases and another had prostatic invasion. Nine of 21 florid von Brunn nests cases were from either the ureter or renal pelvis, whereas all cases of nested variant of urothelial carcinoma arose in the bladder. The ureteral and pelvic florid von Brunn nest cases showed smaller, more variable nests with irregular spacing closely mimicking nested variant of urothelial carcinoma but had a noninfiltrative base and often areas with either a lobular or linear array. Immunohistochemical studies showed nested variant of urothelial carcinoma to have higher MIB-1 expression (8.8% vs. 2.8%, P = 0.01). Nested variant of urothelial carcinoma had nonsignificantly higher p53 positivity (4.2% vs. 1.5%, P = 0.06) and lower p27 positivity (4.7% vs. 7.8%, P = 0.22). Cytokeratin 20 staining was not discriminatory. However, staining with each antibody was widely variable. Wide variation in staining for MIB-1, p53, p27, and cytokeratin 20 was seen in both florid von Brunn nests and nested variant of urothelial carcinoma, such that except for a few cases, a specific cutoff value could not be determined for diagnostic purposes. The findings underscore the importance of morphologic assessment in the distinction of florid von Brunn nests and nested variant of urothelial carcinoma.