2021-05 / February 01
Contributor: Daniel Athanazio

A female patient in her 80s with clinical suspicion of chronic cystitis and gross hematuria underwent cystoscopy showing multifocal erythema and erosions. There was no previous history of bladder surgery or instrumentation. At microscopy, the transurethral resection specimen showed several papillary lesions – the larger lesion measuring 2.6 mm.


1. What is the correct diagnosis?

a. Noninvasive papillary urothelial carcinoma

b. Nephrogenic adenoma

c. Clear cell carcinoma

d. Urothelial carcinoma with microcystic variant morphology

1. Nephrogenic Adenoma

Nephrogenic adenoma may show a broad spectrum of growth patterns including papillary, tubular, and solid. All three patterns are observed in this case. The lesions were diffusely positive for PAX8 and Cytokeratin 7, and entirely negative for GATA3 and p63. We also performed pan-Cytokeratin staining that did not highlight any areas suspicious of stromal invasion.

Some of the small lesions showed a flat pattern – a distinct morphologic presentation of nephrogenic adenoma that had been recently described. The flat pattern of nephrogenic adenoma is usually highlighted by PAX2 or PAX8 stains (see figure 4B).

Regardless of the pattern observed, the observation of epithelial lesions covered by a single layer of cells within the urinary tract mucosa is a valuable clue to consider the diagnosis of nephrogenic adenoma.

1. Rahemtullah A, Oliva E. Nephrogenic adenoma: an update on an innocuous but troublesome entity. Adv Anat Pathol. 2006 Sep;13(5):247-55.

2. Piña-Oviedo S, Shen SS, Truong LD, Ayala AG, Ro JY. Flat pattern of nephrogenic adenoma: previously unrecognized pattern unveiled using PAX2 and PAX8 immunohistochemistry. Mod Pathol. 2013 Jun;26(6):792-8.

Daniel Athanazio
Professor of Medicine, Federal University of Bahia
Imagepat, Laboratory of Pathology
Salvador, Bahia, Brazil


Bladder; Nephrogenic adenoma; PAX8