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Nephrogenic metaplasia (adenomatoid tumors) of bladder
NEPHROGENIC
METAPLASIA
(ADENOMATOID
TUMORS)
OF BLADDER JON A. KASWICK,
M.D.
JERRY
M.D.
WAISMAN,
WILLARD
E. GOODWIN,
M.D.
From the Department of Surgery, Division of Urology, and the Department of Pathology, UCLA School of Medicine, Los Angeles, California
ABSTRACT - Two cases of rare nephrogenic metaplasia of the bladder (adenomatoid bladder tumor) support the theory that these tumors originate as an atypical metaplastic response of urothelium to chronic infection or irritation. That these may also represent mesonephric or mesothelial choristomas is considered. Although benign, they may recur. Therapy should consist of antibiotics and transurethral resection or fulguration.
Nephrogenic metaplasia (nephrogenic adenoma or adenomatoid tumor) of the urinary bladder represents a benign lesion of equivocal origin. Survey of the literature revealed 26 previously reported cases occurring predominantly in young to middle-aged men. l-l6 Reviews of this topic have appeared in the recent urologic literature. l-4 Two patients in whom this lesion developed after rather prolonged and complicated urologic therapy are the subjects of this report.
Case 2
Case Reports Cnse 1 A fifty-seven-year-old man had a twenty-fiveyear history of recurrent calculi with multiple operations for stones. He underwent left ureterolithotomy and YV-plasty of the bladder neck at the UCLA Hospital in 1965. Postoperative escretory urogram was normal, and no lesions were present in the bladder. In September, 1969, after a solitary episode of gross hematuria, two papillary tumors at the bladder neck and above the left ureteral orifice were resected via the urethra. Findings on follow-up cystoscopy in October, 1970, were negative, but repeat cystoscopy a year later demonstrated a tiny papillary lesion above the left ureteral orifice. This lesion also was
CHOLOGY
/
SEPTEMBER
1976
/
treated by endoscopic resection. Cystoscopy and biopsy in November, 1972, revealed chronic inflammation without recurrence of the previous lesions, and cystoscopic findings in January, 1974, were negative. The original urine culture in 1965 grew Pseudomonas, but all subsequent cultures were sterile. The patient was most recently seen in January, 1975, at which time no visible recurrence of the lesion was present.
VOLUME
VIII,
NUMBER
A forty-seven-year-old woman with a one-year history of incontinence was referred to the UCLA Hospital in June, 1973, for management of a urethrovaginal fistula resulting from a MarshallMarchetti-Krantz bladder neck suspension procedure. Unsuccessful attempt at fistula repair had been previously performed elsewhere. Cystoscopy revealed no lesions in the bladder. She underwent a ureteroileocutaneous urinary diversion followed by a transvaginal fistula repair the next month. A Proteus mirabilis-enterobacter urinary infection was treated with appropriate antibiotics. In September, 1973, her urinary tract was reconstituted by ileocystostomy. Findings on follow-up cystoscopy in January, 1974, were negative, but the incontinence recurred. Cystoscopy later
3
283
FIGURE 1. (A to C) Case 1. (A) Original polypoid tumor; surface lined by low columnar cells while stroma has many glandular profiles and congested blood vessels (original magni$cation, x100). (B) Same tissue; spaces lined by low columnar, cuboidal, or squamous cells with foamy cytoplasm and small round nuclei; stroma contains inflammatory cells (original magnification, X 700). (C) Recurrence of tumor, again with columnar metaplasia of bladder lining (original magnijkation, X100). (D and E) Case 2. (D) Polypoid tumor with many glandular profiles and cysts (original magnijcation, X100). (E) Same tissue; cells lining glandular spaces have foamy cytoplasm and pleomorphic nuclei; vesicular, eosinophils are evident in stroma (original magnijication, X 700).
in October, 1974, revealed multiple papillary bladder tumors, and the most prominent of these lesions, located above the left ureteral orifice, was biopsied. Urine culture grew significant numbers of Escherichia coli. Treatment consisted of transurethral resection of the papillary lesions and appropriate antibiotic medication.
284
Pathologic
Observations
The initial specimen from the first patient consisted of eight pieces of tissue, the largest 7 mm. across. These were gray and several had a pink surface with isolated granular areas. Microscopic examination revealed bladder mucosa and muscular tissue with scant transitional epithelium, the
UROLOGY
/ SEPTEMBER1976
/ VOLUMEVIII,
NUMBER3
surface being bare or covered by low columnar cells. Throughout, the tissue was congested and edematous with scattered mononuclear inflammatory cells. Calcium deposits were noted in the lamina propria and on the epithelium. The adenomatoid tumor was seen best in one fragment with a papillary surface and columnar metaplasia (Fig. 1A). The lamina propria beneath contained many tubular structures, some small and others dilated. The tubules were continuous with the surface. Congested blood vessels were conspicuous, and there were inflammatory cells in the stroma. The tubules were lined by columnar, cuboidal, or squamous cells with reticulated cytoplasm and condensed round nuclei (Fig. 1B). There was no significant cytologic atypia, and mitotic figures were not evident. Dilated tubules were filled with an eosinophilic coagulum. The recurrence of the lesion in the first patient was observed in two small fragments of bladder mucosa resembling the original lesion in gross and microscopic features. The tubular structures were less conspicuous, and the cells lining these tubules were generally cuboidal or flat (Fig. 1C). The lesion was not evident in the final biopsy although chronic inflammation was specimen, present. The bladder specimen from the second patient was red and measured 7 by 4 by 3 mm. It had one rough surface and small cysts throughout. Microscopic examination revealed a lesion ahnost identical to that described previously. The surface showed columnar or cuboidal metaplasia, and there was considerable evidence of acute and chronic inflammation. Tubules and cysts filled the lamina propria (Fig. 1D). Compared with the first lesion, nuclei of cells lining the tubules were larger. more vesicular, and pleomorphic (Fig. LE); however, there was no histologic evidence of a malignant process.
disease was present in several of the patients,596 including one of ours, and traumatic rupture of the bladder was seen in several instances.7*” The lesions occurred both as solitary papillomas and multiple tumors, exhibiting a predilection for the bladder base and trigone but certainly not confined to this area. Histologic examination characteristically demonstrated chronic cystitis associated with the typical nephrogenic metaplastic changes described. Mostofi7 alluded to a patient with nephrogenic adenoma in whom bladder carcinoma later developed. Christoffersen and Moeller’ described a case in which histologic atypia developed in a recurrent nephrogenic adenoma. Dow and Young17 reported a case of primary mesonephric adenocarcinoma of the bladder but postulated that malignant degeneration of a nephrogenic pathogenesis. No adenoma was an “unlikely” other incidents of malignant transformation have been reported, and it appears appropriate to regard these as benign lesions.
Review of the 28 reported cases of nephrogenic metaplasia (adenomatoid tumors) of the bladder, including our 2 cases, reveals the following facts. Twenty-three of the patients were men and 5 were women. The age range was eighteen to seventy-one years, with more than 60 per cent of patients less than fifty years of age. Virtually all patients had irritative urinary symptoms, and most of the older men complained as well of lower urinary obstructive symptoms. Urine cultures, when reported, were frequently, although not invariably, positive. Microscopic or gross hematuria generally was present. Chronic calculous
There are two principal theories regarding the pathogenesis of this peculiar lesion. The “embryologic theory” suggests that since the bladder develops from both endoderm (cloaca) and mesoderm (mesonephric duct giving rise to the trigone), nephrogenic tumors represent embryonic rests or choristomas of mesodermally derived elements. This theory would explain the usual location of these tumors in proximity to the trigone, but would not account for the others which occur at sites more remote from the trigone. The “inflammatory theory” postulates that these tumors represent an unusual metaplastic reaction of the urothelium to chronic inflammation or irritation. The latter of these two theories is the more popular, and, indeed, our 2 cases appear to support it. Nevertheless, as suggested in two recent reports on this topic, we would agree that a combination of these two theories may well provide the most plausible explanation. ‘s2 Recently, a third theory was introduced b, Gordon and Kerr,‘based on their experience with the development of this lesion in a renal transplant patient on chronic immunosuppressive therapy. They regarded the lesion as neoplastic in origin, possibly related to a failure of the “immunologic surveillance” mechanism (T-cell function). Although to date no electron microscopic reports of nephrogenic metaplasia (adenomatoid tumors) of the bladder have been published, several investigations studying the ultrastructure of
l~HOI.O(;Y
3
Comment
/
SEPTEMBER
1976
/
VOLUME
VIII.
NUSlBER
285
adenomatoid tumors of the genital tract firmly support the mesothelial origin outside the bladder.g-‘2 Whether or not the genital adenomatoid tumors are related to the bladder lesions remains to be determined; it is likely that this is not the case. Finally, the management of this lesion consists of transurethral resection of fulguration, appropriate antimicrobial therapy, elimination of any source of chronic inflammation, infection, or irritation, and repeated follow-up cystoscopy to detect recurrences which frequently appear. Recently, we have observed at an &liated hospital (Harbor General Hospital, Torrance, California) 2 additional patients with this lesion, indicating that the tumor may not be as rare as previously considered. Los
Angeles, California 90024 (DR. KASWICK)
References KALLOOR, G. J., and SHAW, R. E.: Nephrogenic adenoma of the bladder, Br. J. Urol. 46: 91 (1974). TANEFA, 0. P., et al. : Nephrogenic adenoma of the urinary bladder, Br. J. Urol. 46: 97 (1974). ALLAN, E.: Nephrogenic adenoma of the bladder, J. Urol. 113: 35 (1975). GORDON, H. L., and KERR, S. G.: Nephrogenic adenoma of bladder in immunosuppressed renal transplantation, Urology 5: 275 (1975).
286
5. SUSSMAN, E. B., BRICE, M., II, and GRAY, G. F.: Nephrogenic metaplasia of the bladder, J. Urol. 111: 34 (1974). 6. CHRISTOFFERSEN, J., and MOELLER, J. E.: Adenomatoid tumors of the urinary bladder, Stand. J. Urol. Nephrol. 6: 295 (1972). of bladder epithelium, 7. MOSTOFI, F. K.: Potentialities J. Urol. 71: 705 (1954). adenoma of the bladder, 8. HASEN, H. B.: Nephrogenic ibid. 88: 629 (1962). 9. MARCUS, J. B., and LYNN, J. A.: Ultrastructural comparison of an adenomatoid tumor, lymphangioma, hemangioma, and mesothelioma, Cancer 25: 171(1970). 10. MACKAY, B., BENNINGTON, J. L., and SKOGLUND, R. . The adenomatoid tumor: fine structural evidence r”.. or a mesothelial origin, ibid. 27: 109 (1971). 11. SALAZAR, H., KANBOUR, A., and BURGESS, F.: Ultrastructure and observations on the histogenesis of mesotheliomas “adenomatoid tumors” of the female genital tract, ibid. 29: 141 (1972). 12. TAXY, J. B., BATTIFORA, H., and OYASU, R.: Adenomatoid tumors: a light microscopic, histochemical, and ultrastructural study, ibid. 34: 306 (1974). 13. DAVIS, T. A.: Hamartoma of the urinary bladder, Northwest Med. 48: 182 (1949). Ade14. FRIEDMAN, N. B., and KUHLENBECK, H.: nomatoid tumors of the bladder producing renal structures (nephrogenic adenomas), J. Urol. 64: 657 (1950). 15. BORSKI, A. A.: Hamartoma of the bladder, ibid. 104: 718 (1970). metaplasia (neph16. GOLDMAN, R. L.: Nephrogenic rogenic adenoma, adenomatoid tumor) of the bladder, ibid. 108: 565 (1972). 17. Dow, J. A., and YOUNG, J. D., JR.: Mesonephric adenocarcinoma of the bladder, ibid. 100:466 (1968).
UROLOGY
/
SEPTEMBER 1976 /
VOLUME VIII, NUMBER 3
METAPLASIA
(ADENOMATOID
TUMORS)
OF BLADDER JON A. KASWICK,
M.D.
JERRY
M.D.
WAISMAN,
WILLARD
E. GOODWIN,
M.D.
From the Department of Surgery, Division of Urology, and the Department of Pathology, UCLA School of Medicine, Los Angeles, California
ABSTRACT - Two cases of rare nephrogenic metaplasia of the bladder (adenomatoid bladder tumor) support the theory that these tumors originate as an atypical metaplastic response of urothelium to chronic infection or irritation. That these may also represent mesonephric or mesothelial choristomas is considered. Although benign, they may recur. Therapy should consist of antibiotics and transurethral resection or fulguration.
Nephrogenic metaplasia (nephrogenic adenoma or adenomatoid tumor) of the urinary bladder represents a benign lesion of equivocal origin. Survey of the literature revealed 26 previously reported cases occurring predominantly in young to middle-aged men. l-l6 Reviews of this topic have appeared in the recent urologic literature. l-4 Two patients in whom this lesion developed after rather prolonged and complicated urologic therapy are the subjects of this report.
Case 2
Case Reports Cnse 1 A fifty-seven-year-old man had a twenty-fiveyear history of recurrent calculi with multiple operations for stones. He underwent left ureterolithotomy and YV-plasty of the bladder neck at the UCLA Hospital in 1965. Postoperative escretory urogram was normal, and no lesions were present in the bladder. In September, 1969, after a solitary episode of gross hematuria, two papillary tumors at the bladder neck and above the left ureteral orifice were resected via the urethra. Findings on follow-up cystoscopy in October, 1970, were negative, but repeat cystoscopy a year later demonstrated a tiny papillary lesion above the left ureteral orifice. This lesion also was
CHOLOGY
/
SEPTEMBER
1976
/
treated by endoscopic resection. Cystoscopy and biopsy in November, 1972, revealed chronic inflammation without recurrence of the previous lesions, and cystoscopic findings in January, 1974, were negative. The original urine culture in 1965 grew Pseudomonas, but all subsequent cultures were sterile. The patient was most recently seen in January, 1975, at which time no visible recurrence of the lesion was present.
VOLUME
VIII,
NUMBER
A forty-seven-year-old woman with a one-year history of incontinence was referred to the UCLA Hospital in June, 1973, for management of a urethrovaginal fistula resulting from a MarshallMarchetti-Krantz bladder neck suspension procedure. Unsuccessful attempt at fistula repair had been previously performed elsewhere. Cystoscopy revealed no lesions in the bladder. She underwent a ureteroileocutaneous urinary diversion followed by a transvaginal fistula repair the next month. A Proteus mirabilis-enterobacter urinary infection was treated with appropriate antibiotics. In September, 1973, her urinary tract was reconstituted by ileocystostomy. Findings on follow-up cystoscopy in January, 1974, were negative, but the incontinence recurred. Cystoscopy later
3
283
FIGURE 1. (A to C) Case 1. (A) Original polypoid tumor; surface lined by low columnar cells while stroma has many glandular profiles and congested blood vessels (original magni$cation, x100). (B) Same tissue; spaces lined by low columnar, cuboidal, or squamous cells with foamy cytoplasm and small round nuclei; stroma contains inflammatory cells (original magnification, X 700). (C) Recurrence of tumor, again with columnar metaplasia of bladder lining (original magnijkation, X100). (D and E) Case 2. (D) Polypoid tumor with many glandular profiles and cysts (original magnijcation, X100). (E) Same tissue; cells lining glandular spaces have foamy cytoplasm and pleomorphic nuclei; vesicular, eosinophils are evident in stroma (original magnijication, X 700).
in October, 1974, revealed multiple papillary bladder tumors, and the most prominent of these lesions, located above the left ureteral orifice, was biopsied. Urine culture grew significant numbers of Escherichia coli. Treatment consisted of transurethral resection of the papillary lesions and appropriate antibiotic medication.
284
Pathologic
Observations
The initial specimen from the first patient consisted of eight pieces of tissue, the largest 7 mm. across. These were gray and several had a pink surface with isolated granular areas. Microscopic examination revealed bladder mucosa and muscular tissue with scant transitional epithelium, the
UROLOGY
/ SEPTEMBER1976
/ VOLUMEVIII,
NUMBER3
surface being bare or covered by low columnar cells. Throughout, the tissue was congested and edematous with scattered mononuclear inflammatory cells. Calcium deposits were noted in the lamina propria and on the epithelium. The adenomatoid tumor was seen best in one fragment with a papillary surface and columnar metaplasia (Fig. 1A). The lamina propria beneath contained many tubular structures, some small and others dilated. The tubules were continuous with the surface. Congested blood vessels were conspicuous, and there were inflammatory cells in the stroma. The tubules were lined by columnar, cuboidal, or squamous cells with reticulated cytoplasm and condensed round nuclei (Fig. 1B). There was no significant cytologic atypia, and mitotic figures were not evident. Dilated tubules were filled with an eosinophilic coagulum. The recurrence of the lesion in the first patient was observed in two small fragments of bladder mucosa resembling the original lesion in gross and microscopic features. The tubular structures were less conspicuous, and the cells lining these tubules were generally cuboidal or flat (Fig. 1C). The lesion was not evident in the final biopsy although chronic inflammation was specimen, present. The bladder specimen from the second patient was red and measured 7 by 4 by 3 mm. It had one rough surface and small cysts throughout. Microscopic examination revealed a lesion ahnost identical to that described previously. The surface showed columnar or cuboidal metaplasia, and there was considerable evidence of acute and chronic inflammation. Tubules and cysts filled the lamina propria (Fig. 1D). Compared with the first lesion, nuclei of cells lining the tubules were larger. more vesicular, and pleomorphic (Fig. LE); however, there was no histologic evidence of a malignant process.
disease was present in several of the patients,596 including one of ours, and traumatic rupture of the bladder was seen in several instances.7*” The lesions occurred both as solitary papillomas and multiple tumors, exhibiting a predilection for the bladder base and trigone but certainly not confined to this area. Histologic examination characteristically demonstrated chronic cystitis associated with the typical nephrogenic metaplastic changes described. Mostofi7 alluded to a patient with nephrogenic adenoma in whom bladder carcinoma later developed. Christoffersen and Moeller’ described a case in which histologic atypia developed in a recurrent nephrogenic adenoma. Dow and Young17 reported a case of primary mesonephric adenocarcinoma of the bladder but postulated that malignant degeneration of a nephrogenic pathogenesis. No adenoma was an “unlikely” other incidents of malignant transformation have been reported, and it appears appropriate to regard these as benign lesions.
Review of the 28 reported cases of nephrogenic metaplasia (adenomatoid tumors) of the bladder, including our 2 cases, reveals the following facts. Twenty-three of the patients were men and 5 were women. The age range was eighteen to seventy-one years, with more than 60 per cent of patients less than fifty years of age. Virtually all patients had irritative urinary symptoms, and most of the older men complained as well of lower urinary obstructive symptoms. Urine cultures, when reported, were frequently, although not invariably, positive. Microscopic or gross hematuria generally was present. Chronic calculous
There are two principal theories regarding the pathogenesis of this peculiar lesion. The “embryologic theory” suggests that since the bladder develops from both endoderm (cloaca) and mesoderm (mesonephric duct giving rise to the trigone), nephrogenic tumors represent embryonic rests or choristomas of mesodermally derived elements. This theory would explain the usual location of these tumors in proximity to the trigone, but would not account for the others which occur at sites more remote from the trigone. The “inflammatory theory” postulates that these tumors represent an unusual metaplastic reaction of the urothelium to chronic inflammation or irritation. The latter of these two theories is the more popular, and, indeed, our 2 cases appear to support it. Nevertheless, as suggested in two recent reports on this topic, we would agree that a combination of these two theories may well provide the most plausible explanation. ‘s2 Recently, a third theory was introduced b, Gordon and Kerr,‘based on their experience with the development of this lesion in a renal transplant patient on chronic immunosuppressive therapy. They regarded the lesion as neoplastic in origin, possibly related to a failure of the “immunologic surveillance” mechanism (T-cell function). Although to date no electron microscopic reports of nephrogenic metaplasia (adenomatoid tumors) of the bladder have been published, several investigations studying the ultrastructure of
l~HOI.O(;Y
3
Comment
/
SEPTEMBER
1976
/
VOLUME
VIII.
NUSlBER
285
adenomatoid tumors of the genital tract firmly support the mesothelial origin outside the bladder.g-‘2 Whether or not the genital adenomatoid tumors are related to the bladder lesions remains to be determined; it is likely that this is not the case. Finally, the management of this lesion consists of transurethral resection of fulguration, appropriate antimicrobial therapy, elimination of any source of chronic inflammation, infection, or irritation, and repeated follow-up cystoscopy to detect recurrences which frequently appear. Recently, we have observed at an &liated hospital (Harbor General Hospital, Torrance, California) 2 additional patients with this lesion, indicating that the tumor may not be as rare as previously considered. Los
Angeles, California 90024 (DR. KASWICK)
References KALLOOR, G. J., and SHAW, R. E.: Nephrogenic adenoma of the bladder, Br. J. Urol. 46: 91 (1974). TANEFA, 0. P., et al. : Nephrogenic adenoma of the urinary bladder, Br. J. Urol. 46: 97 (1974). ALLAN, E.: Nephrogenic adenoma of the bladder, J. Urol. 113: 35 (1975). GORDON, H. L., and KERR, S. G.: Nephrogenic adenoma of bladder in immunosuppressed renal transplantation, Urology 5: 275 (1975).
286
5. SUSSMAN, E. B., BRICE, M., II, and GRAY, G. F.: Nephrogenic metaplasia of the bladder, J. Urol. 111: 34 (1974). 6. CHRISTOFFERSEN, J., and MOELLER, J. E.: Adenomatoid tumors of the urinary bladder, Stand. J. Urol. Nephrol. 6: 295 (1972). of bladder epithelium, 7. MOSTOFI, F. K.: Potentialities J. Urol. 71: 705 (1954). adenoma of the bladder, 8. HASEN, H. B.: Nephrogenic ibid. 88: 629 (1962). 9. MARCUS, J. B., and LYNN, J. A.: Ultrastructural comparison of an adenomatoid tumor, lymphangioma, hemangioma, and mesothelioma, Cancer 25: 171(1970). 10. MACKAY, B., BENNINGTON, J. L., and SKOGLUND, R. . The adenomatoid tumor: fine structural evidence r”.. or a mesothelial origin, ibid. 27: 109 (1971). 11. SALAZAR, H., KANBOUR, A., and BURGESS, F.: Ultrastructure and observations on the histogenesis of mesotheliomas “adenomatoid tumors” of the female genital tract, ibid. 29: 141 (1972). 12. TAXY, J. B., BATTIFORA, H., and OYASU, R.: Adenomatoid tumors: a light microscopic, histochemical, and ultrastructural study, ibid. 34: 306 (1974). 13. DAVIS, T. A.: Hamartoma of the urinary bladder, Northwest Med. 48: 182 (1949). Ade14. FRIEDMAN, N. B., and KUHLENBECK, H.: nomatoid tumors of the bladder producing renal structures (nephrogenic adenomas), J. Urol. 64: 657 (1950). 15. BORSKI, A. A.: Hamartoma of the bladder, ibid. 104: 718 (1970). metaplasia (neph16. GOLDMAN, R. L.: Nephrogenic rogenic adenoma, adenomatoid tumor) of the bladder, ibid. 108: 565 (1972). 17. Dow, J. A., and YOUNG, J. D., JR.: Mesonephric adenocarcinoma of the bladder, ibid. 100:466 (1968).
UROLOGY
/
SEPTEMBER 1976 /
VOLUME VIII, NUMBER 3