Answer: Villous adenoma with high grade dysplasia

Histology: This lesion is villoglandular, consisting of papillary fronds lined by pseudostratified columnar epithelium with numerous goblet cells. In most areas, polarity is maintained with nuclei oriented towards the base of the cell with maintenance of abundant apical cytoplasm. Focally, there is a loss of mucin with cells becoming less polarized and focal cribriform formation. If this lesion were present within the colon, it would be classic for a villous adenoma with focal high-grade dysplasia.

Discussion: Assessment of glandular lesions within the bladder and urethra is done in an analogous fashion as to how one would diagnose similar lesions present within the intestine. The spectrum of lesions that occur within the bladder and urethra range from villous adenoma to villous adenoma with high-grade dysplasia to villous adenoma with infiltrating adenocarcinoma. One may also see in situ adenocarcinoma arising in a more flat or polypoid mucosa without a villiform architecture. Finally, one can have infiltrating adenocarcinoma similar to what is seen in the intestine without an identifiable precursor lesion. Paralleling the situation seen within the intestine, if villous adenoma or villous adenoma with high-grade dysplasia is totally removed from the bladder or urethra, the treatment is curative. However, if the lesion has not been entirely sampled, and the histology shows villous adenoma or villous adenoma with high-grade dysplasia, complete sampling must be performed to rule out the presence of focally infiltrating adenocarcinoma. Villous adenomas may also occur within the urachus, located at the dome or anterior wall of the bladder.

The current lesion lacks individual glands extending into the underlying stroma, diagnostic of infiltrating adenocarcinoma. Infiltrating adenocarcinoma arising in the urethra or bladder may also show a mucinous histology with lakes of extra-cellular mucin lined by atypical columnar epithelium. Mucin positive signet cells are also typically seen in many adenocarcinomas arising within the bladder and urethra. Whenever one is presented with histology of a villous adenoma or adenocarcinoma involving the bladder, it is necessary to rule out the possibility of a metastasis from the colon. Adenocarcinomas of the colon may either directly invade or metastasize to the bladder, whereby they may closely mimic a primary villous adenoma or adenocarcinoma of the bladder. These metastases to the bladder may on occasion develop well-formed villiform fronds with an area similar in morphology to what is seen in the current case, although elsewhere there will be more typical findings of adenocarcinoma. Whereas adenocarcinomas of the colon can invade the bladder and present with a villiform morphology, a villiform pattern has not been seen with adenocarcinomas of the colon infiltrating the prostate and prostatic urethra. The lack of such a villiform pattern within colon cancers invading into the prostate and prostatic urethra probably relate to the lack of a large lumen for which this morphology requires for its growth pattern. Within the prostatic urethra, one must also consider other papillary glandular lesions. The most common entity entering into the differential diagnosis is prostatic duct adenocarcinoma, which most commonly has a papillary or cribriform morphology. Prostatic duct adenocarcinomas typically have amphophilic cytoplasm, yet uncommonly may reveal clear cytoplasm. These unusual prostatic duct adenocarcinomas with pseudostratified columnar cells and clear cytoplasm lack mucin-filled goblet cells. Mucin stains are be negative in prostatic duct adenocarcinoma, and stains for prostate specific antigen and prostate specific acid phosphatase are strongly positive.