Mehemet Yaldiz, Ali Kemal Uzunlar, Enver Ozdmemir, and Mehmet Ozaydin
Department of Pathology, Dicle University, Faculty of Medicine, Diyarbakir, Turkey
Department of Urology, dicle university, Facultiy of Medicien, Diyarbakir, Turkey

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Nephrogenic adenoma is an uncommon, benign lesion of the lower urinary tractus, occuring as an epithelial response to trauma or infection. Herewith, we report a patient with nephrogenic adenoma in the urinary bladder. Histhologically, the tumor consists of cystic and tubular structures resembling the distal part of the nephron. Local resection with fulguration of the base of the lesion, long-term antimicrobial therapy and periodic control with cystoscopy is the established modality of treatment. An increased awareness of nephrogenic adenoma by urologists and pathologists may lead to its more frequent diagnosis.
Key Words: Nephrogenic adenoma, Bladder tumors.

The term nephrogenic adenoma was first introduced by Friedman and Kuhlenbeck in 1950, to describe an adenomatoid tumor that contained epithelial-lined tubules resembling the developing nephron (1). While the gross appearance of these lesions is indistinguishable from the more common papillary transitional cell carcinoma, the microscopic appearance is distinctive. The behavior of nephrogenic adenoma is benign. These lesions are seen most commonly in men in the second and third decades of life. Usually, they occur in a setting of chronic inflammation, previous surgery, infection, trauma or stone but may also be seen in immunosuppressed patients (2,3).
We report a patient with nephrogenic adenoma of bladder and discuss the etiology and pathological features as well as therapeutic management to understand better this unusual bladder lesion on the basis of the available literature.

A 25-year-old man was admitted with the complaints of dysuria, hematuria, pain in bilateral flank and the left iliac fossa to the outpatient Department of Dicle University Hospital, Diyarbak‰Ó. He had the history of bilateral nephrolitotomy and cystolitotomy operation five years ago, because of bilateral pelvicalyceal stones and bladder stone on excretory urographic examination. During that operations, he had undergone urethral catheterisation for two-weeks. An excretory urogram was unremarkably normal at presentation. Urine culture examination showed E. coli infection, which was treated accordingly. During cystoscopy, multiple papillary lesions resembling low grade transitional cell carcinoma, involving the bladder wall and the trigone were noted. Biopsy specimens contained small cysts with single layered low cuboidal epithelium consistent with nephrogenic adenoma. The stroma contained an inflammatory infiltrate (Fig 1,2). At operation, 3 weeks later, all the lesions were resected and fulgurated endoscopically. Follow-up cystoscopic examinations up to nine months revealed no recurrence.

The etiology of nephrogenic adenoma is unclear. Several authors suggest that it arises from embryonic mesonephric tissue, whereas the majority of reports indicate that it is the response of urethelium to tissue injury (4,5). Moreover, in all children and in the overwhelming majority of adults, the adenoma was developed in the urethelium that had been exposed to previous surgery or long term inflammation. Its multifocal appearance, ranging from the trigone to the dome, would suggest an acquired lesion as opposed to embryonic persistence (6). The presence of localized tumor at definitive sites of injuries is also important. Localized nephrogenic adenoma in infected diverticula of the bladder and urethra may also demonstrate the involved bladder and urethral epithelium, and its metaplastic response to injury. This unusual manifestation of the epithelium concurs with MostofiŽŐs theory of the multipotantiality of the urothelium.(7).
The clinical features of nephrogenic adenoma ranges from gross hematuria to the more common signs of the bladder irritability secondary to inflammation (8). In addition, lesions have been found incidentally in cystectomy specimens removed for carcinoma as well as in resected specimens of diverticula of the bladder and the urethra (7,9).
The cystoscopic appearance of nephrogenic adenoma is extremely variable. As a rule, there are polyps which may have papillary appearance. Not infrequently the polyps appear as edematous areas which may be extensive and difficult to demarcate. Nephrogenic adenoma can, therefore, be mistaken for inflammatory as well as neoplastic disease (2,3).
Histologically, nephrogenic adenoma shows a constant and characteristic morphology. The tumor contains cystic and tubuler structures with a single layer of cuboidal or cylindric epithelium resembling the epithelial layer of the distal part of the nephron (1,10). Ultrastructural studies by Molland et al. revealed that the tubules do not have specialized features of any part of the adult nephron (10). In addition, the tubuler cells lacked features characteristic of urothelium. However, Imahori and Magoss showed that under electron microscopic examination the presence of branching and epithelial budding suggests ureteral bud branching seen in embryonic development of the fetal kidney (11). These findings would suggest metaplasia of the urethelium as opposed to a neoplastic process inferred by the term of nephrogenic adenoma.
The major concern in regard to nephrogenic adenoma is the question of its neoplastic potential. Although it has been associated in the bladder with concurrent carcinoma and has been related to mesonephric adenocarcinoma, its development into frank carcinoma has not been documented. Nephrohenic adenoma, moreover, may present with pseudoinfiltrative growth giving rise to difficulties in differential diagnosis (12).
The diagnosis is based on biopsy, and the specimen should include muscle to permit distinction between pseudoinfiltration and true infiltration (3). Although cystectomy and augmentation cystoplasty have been used, most of the patients are well controlled with endoscopic fulguration (8). Because of the benign nature of the disease and the potantial pathogenic bladder injury, limited endoscopic manipulation and long-term antimicrobial therapy are recommended (13). In addition, cytology and periodic cystoscopy are recommended because of the presence of a reactive and proliferative bladder epithelium, and the lack of knowledge in regard to the naturel history of nephrogenic adenoma.

1. Friedman NB, Kuhlenbeck H. Adenomatoid tumors of the bladder reproducing renal structures ( nephrogenic adenoma ). J Urol 1950; 64: 657-670.
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9. Peterson LJ, Matsumato LM. Nephrogenic adenoma in urethral diverticulum. Urology 1978; 11: 193-195.
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11.r Imahori S, and Magoss IV. Nephrogenic adenoma of the bladder. Clinical and ultrastructral study. Urology 1980; 16: 310-315.
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13. Lugo M, Peterson RO, Elfenbein B, Stein BS, Duker NJ. Nephrogenic metaplasia of the ureter. Am J Clin Pathol 1983; 80: 92-97.


Fig. 1. Low power photomicrograph shows typical papillary and tubular configuration of nephrogenic adenoma. (H&E, Orginal magnification 80x)

Fig. 2. High power photomicrograph illustrates cysts and tubules lined with a single layer of epithelial cells resembling renal tubular epithelium. Interstitium contains numerous mononuclear inflammatory cells. (H&E, Orginal magnification 160x).

Nagoya City University
Medical School