Older Female Presented with Hematuria

Specimen Type:

Bladder

History:

A 94 year-old woman presented with hematuria. Subsequent studies revealed a severely hydronephrotic, non-functioning right kidney. On cystoscopy, she was found to have a 2.0 cm diameter papillary mass overlying the right ureteral orifice. Transurethral resection was done.

Pathologic Features:

The histological features are similar to those of a colonic tubulo-villous adenoma. The tumor consists of pointed or blunt finger-like processes lined by pseudostratified columnar epithelium (Fig. 1.1, 1.2). The abrupt transition from urothelium to columnar epithelium is characteristic (Fig. 1.1). Coexistent intestinal metaplasia with goblet cells is also seen (Fig. 1.2). There is nuclear hyperchromasia, nuclear stratification and overcrowding, and prominent nucleoli (Fig.1.3). Architecturally-distorted glands infiltrate the lamina propria with an accompanying desmoplastic response (Fig. 1.4). There is no muscularis propria in the biopsy for evaluation.

Differential Diagnosis:

The differential diagnostic considerations include cystitis cystica and glandularis (Fig. 1.5, Fig. 1.6), villous adenoma arising in urinary bladder (Fig. 1.7, Fig.1.8), adenocarcinoma of bladder – colonic type (Fig. 1.9), and adenocarcinoma of colon with secondary bladder involvement.

Diagnosis:

Well-Differentiated Adenocarcinoma Arising in Villous Adenoma of Bladder

Key Features:

  • An uncommon neoplasm
  • Usually involves urachus, dome, and trigone of the urinary bladder; rarely, ureter (Fig.1.10) or urethra may be affected
  • Presents with hematuria and irritative symptoms
  • A mass usually identified on cystoscopy
  • Histologically identical to its colonic counterpart
  • Differential diagnosis includes cystitis glandularis (intestinal type), well-differentiated adenocarcinoma of bladder (enteric type), and secondary involvement of bladder by a colonic adenocarcinoma
  • Coexistent adenocarcinoma is seen in about 35% of villous adenomas of bladder
  • An adequate tissue sample and good clinical history are essential before rendering a diagnosis of villous adenoma of bladder
  • Simple excision is curative. Risk of recurrence is low
  • Left untreated, its biological behavior is uncertain. It may be responsible for some cases of bladder adenocarcinoma

Immunohistochemical stains are not required for the diagnosis and were not performed in this case. The majority of villous adenomas of the bladder show reactivity for cytokeratin 20 (CK20) and carcinoembryonic antigen (CEA). Immunoreactivity for cytokeratin 7 (CK7) is seen in about half of the cases. About one-fifth of cases are reactive for epithelial membrane antigen (EMA). Colonic adenocarcinoma shows immunoreactivity for CEA, EMA, and CK20 and is negative for CK7. Immunohistochemical profile may be used in distinguishing primary villous adenoma of the bladder from colonic adenocarcinoma secondarily involving bladder; however, caution is warranted in interpreting immunohistochemical results (1).

Discussion: Villous adenoma of the urinary tract is uncommon (2). It occurs in the elderly patients with a predilection for the urachus, dome, and trigone of the urinary bladder; rare cases involve the ureters (Fig.1.10) or urethra (3). Typical presenting features include hematuria and irritative voiding symptoms. Tumors involving urachus may present with mucusuria due to abundant mucin production (4,5). Cystoscopy usually identifies a mass.

The light microscopic features of villous adenoma of the bladder are virtually identical to the colonic counterparts. Distinction of villous adenoma of the bladder with coexistent adenocarcinoma from secondary involvement by colonic cancer may be difficult on morphological grounds alone, especially in a small biopsy sample (6). In such cases, clinical presentation, endoscopic examination, and radiographic studies are helpful in locating the primary site. Rare cases of coexistent squamous cell carcinoma have also been reported (7). A limited biopsy sample may only show changes of villous adenoma. Further compounding this problem is the difficulty in orienting tissue fragments removed by transurethral resection. Accordingly, diagnosis of villous adenoma of the urinary tract should be made only after adequate tissue sampling and consideration of secondary involvement from other sites such as the colon, prostate, and female genital tract.

The potential for malignant transformation of the villous adenoma of the bladder is unknown because most lesions are completely resected for histological evaluation. Villous adenoma is rarer than adenocarcinoma. The possibility that coexistent villous adenoma and adenocarcinoma may be an epiphenomenon cannot be ruled out with certainity. Nevertheless, the progression from metaplasia in cystitis glandularis to dysplasia in villous adenoma and adenocarcinoma has been proposed for the urinary tract, analogous to the adenoma-carcinoma sequence for colonic cancer (8,9). Rare cases demonstrating such morphologic continuum have been reported (10).

Patients with isolated villous adenoma have an excellent prognosis and most are cured by simple excision. Recurrence of the original tumor or subsequent development of adenocarcinoma is rarely seen. Those with coexistent adenocarcinoma are at risk for multiple recurrences or distant metastases and benefit from aggressive treatment.

Follow-up:Additional studies in this patient revealed two metastatic pulmonary nodules. Because of advanced age and poor health, aggressive therapy was not provided. Three months after diagnosis, the patient was alive with persistent cancer.

References:

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  2. Cheng L, Montironi R, Bostwick DG. Villous adenoma of the urinary tract: A report of 23 cases, including 8 with coexistent adenocarcinoma. Am J Surg Pathol 1999; 23(7):764-71.
  3. Tran KP, Epstein JI. Mucinous adenocarcinoma of urinary bladder type arising from the prostatic urethra. Distinction from mucinous adenocarcinoma of the prostate. Am J Surg Pathol 1996; 20(11):1346-50.
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  10. Lucas DR, Lawrence DW, McDevitt WJ, Giacomelli F. Mucinous papillary adenocarcinoma of the bladder arising within a villous adenoma of urachal remnants. J Urologic Pathol 1994; 2:173-82.