Bladder Neck Tumor in an Older Female

Specimen Type:

Bladder

History:

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.

Pathologic Features:

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.

Differential Diagnosis:

  • Nephrogenic metaplasia (Fig 4)
  • Urothelial carcinoma with glandular differentiation
  • Metastatic clear cell carcinoma

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.

Diagnosis:

Clear cell adenocarcinoma of bladder primary with invasion into muscularis propria.

Key Features:

  • Infiltrating pattern
  • Tubulocystic architecture
  • Cells have abundant clear or eosinophilic cytoplasm with hobnail cell features
  • Significant cytologic atypia including enlarged nuclei, prominent nucleoli and mitotic figures

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 Common
Glycogen in cytoplasm Rare Common and abundant
Nuclear atypia and mitotic figures Rare Common

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.

References:

  1. Bostwick DG, Lopez-Beltran A. Bladder biopsy interpretation. United Pathology Press 1999, pp 174-175.
  2. Drew PA, Murphy WM, Civantos F, Speights VO. The histogenesis of clear cell adenocarcinoma of the lower urinary tract. Case series and review of the literature. Hum Pathol. 1996 Mar;27(3):248-52.
  3. Young RH, Scully RE. Clear cell adenocarcinoma of the bladder and urethra. A report of three cases and review of the literature. Am J Surg Pathol. 1985 Nov;9(11):816-26.
  4. Chor PJ, Gaum LD, Young RH. Clear cell adenocarcinoma of the urinary bladder: report of a case of probable mullerian origin. Mod Pathol. 1993 Mar;6(2):225-8.