A 43-year- old woman presented with distended neurogenic bladder. Cystoscopy showed an exophytic 3 cm bladder neck mass which clinically appeared to have ball-valve effect into the urethra, causing urinary obstruction.
Multiple fragments of urothelium-lined mucosa with submucosa and muscularis propria are present. Most pieces show papillary, tubular and cystic proliferation of atypical epithelial cells (Fig 1). In some areas complex papillary structures predominate and in other areas variable small to large tubular structures predominate. Invasion into the lamina propria and muscularis propria is identified. The proliferating epithelial cells are variable in their appearance ranging from flattened to cuboidal to columnar and areas with elongate hobnail appearance ( Fig 2).The cytoplasm of the cells are eosinophilic with hyaline-like secretions (Fig 3). The nuclei are intermediate to large in size, often with prominent nucleoli. Brisk mitotic activity is present.
Nephrogenic metaplasia: Nephrogenic metaplasia is most common in the bladder but may involve the urethra, urether and renal pelvis. Most patients have a history of an operative procedure or one or more irritants, including calculi, trauma, and cystitis. It is usually 1cm or less in diameter and single, but exceptions occur. Although tubular pattern is the most common, polypoid, papillary and cystic patterns are also seen. The tubules appear as small, round, hollow acini reminiscent of renal tubules. The tubules, cysts, and papillae are lined by flattened, cuboidal or low columnar cells with scant cytoplasm, and hobnail cells are appreciated in up to 70% of the cases. Nuclear abnormalities are uncommon and, when present, appear reactive or degenerative.
Urothelial carcinoma with glandular differentiation: Typical urothelial carcinoma should be invariably identified, and the “glands” with lumen formation are surrounded by cells with pseudostratified appearance and superficial cell differentiation of urothelium, although typical glands lined by single layer columnar epithelium can be present.
Metastatic clear cell carcinoma: Metastatic clear cell carcinoma should be excluded in female patients and requires clinical correlation. Renal cell carcinoma rarely metastasized to the bladder and should be excluded; recognition of the typical sinusoidal vascular pattern, lack of tubular differentiation, absence of mucin, and clinical features should resolve this issue.
Clear cell adenocarcinoma of bladder primary with invasion into muscularis propria.
Key Features:
Table 1 Features distinguishing nephrogenic adenoma from clear cell
Features
Nephrogenic Adenoma
Clear Cell Adenocarcinoma
Gender predominance
Male
Female
Age
33% < 30 years
All > 43 years
Associated genitourinary conditions
Very common
Absent
Size
Usually small
Often large
Solid growth pattern
Rare
Common
Clear cells
Uncommon
Glycogen in cytoplasm
Common and abundant
Nuclear atypia and mitotic figures
Comment: Clear cell adenocarcinoma is very rare in the bladder and more common in the urethra. Clear cell adenocarcinoma is typically solid or papillary and located in the trigone or posterior wall. Microscopically, it invariably has tubular component, often with cystic dilatation. The lining cells are flat, cuboidal or columnar and characteristic “hobnail” cells are at least focally present. There is typically significant nuclear pleomorphism with frequent mitotic figures. The cytoplasm is clear because of abundant glycogen and focal cytoplasmic and luminal mucin. The major differential diagnostic consideration is nephrogenic metaplasia. Nephrogenic metaplasia is typically a small lesion with minimal cytologic atypia; it may infilatrate the muscular wall, and the presence of this feature should not be used as a diagnostic criterion for malignancy.
