Discussion:

Proliferative or reactive changes occurring in von Brunn nests which acquire luminal spaces, become cystically dilated (cystitis cystica), undergo glandular metaplasia (cystitis glandularis) or intestinal type metaplasia.

Extremely common incidental finding.

Develops in the setting of chronic mucosal irritation or inflammation.

Cystitis cystica and cystitis glandularis are frequently coexisting interrelated lesions.

Bladder neck and trigone are most common sites.

Reactive process in response to chronic irritation, infection, calculi, outlet obstruction, catheterization.

Occasionally appears as polypoid or papillary mass on cystoscopy

• Often exhibit a vaguely lobular distribution of invaginations
• Noninfiltrative growth and variable connection to surface

Abundant urothelial von Brunn nests

Gland-like lumens with columnar or cuboidal cells (cystitis glandularis).

Cystically dilated lumens or cystic cavities filled with eosinophilic fluid (cystitis cystica).

Majority of cases show coexistence of both patterns.

Cells lack significant atypia, mitotic activity, stromal reaction and muscular invasion

• Degenerative atypia occasionally present

Replacement of urothelium by benign colonic or small intestinal epithelium, with presence of mucin producing goblet cells.

Intestinal or colonic metaplasia: glandular epithelium with mucin secreting goblet cells (single or aggregates) replacing surface mucosa and von Brunn nests.

May coexist with cystitis glandularis, characterized by formation of glandular structures in lamina propria within von Brunn nests that have an innermost lining of columnar or cuboidal cells bound by transitional cells at periphery.

Metaplastic reactive alteration induced by chronic inflammation or irritation.

Clinical Features: Hematuria, dysuria, urgency or obstructive symptoms.

Variable presence of Paneth cells (small, intestine-like) or neuroendocrine cells (rare).

Mucin may be occasionally extravasated into the stroma.

Urothelial carcinoma with villoglandular differentiation (UCVGD) is a rare aggressive variant of urothelial carcinoma.

It is usually associated with high-grade urothelial carcinoma or rarely adenocarcinoma.

Glandular differentiation is defined by the presence of true glandular spaces, usually tubular or gland-like lumina, or with morphology similar to enteric adenocarcinomas and variable mucin production.

Common Sites: Kidney and Bladder.

Presence of true glandular spaces

• Cytoplasmic mucin is seen in normal urothelium and not diagnostic of glandular differentiation

Glands are of either tubular or enteric type, with a single layer of neoplastic columnar cells radially arranged around a lumen, with or without mucin production.

May resemble enteric adenocarcinomas.

May have signet ring morphology, with neoplastic signet ring cells floating in pools of mucin.