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Intestinal metaplasia and dysplasia of prostatic urethra secondary to stricture
INTESTINAL METAPLASIA AND DYSPLASIA OF PROSTATIC URETHRA SECONDARY TO STRICTURE R . MAUNG, M .B ., B .S ., ER.C.P(C .) J . K . KELLY, M .B., B .S., ER .C .P(C .) D . A . GRACE, M .D . From the Departments of Pathology and Urology, Foothills Hospital and the University of Calgary, Calgary, and Department of Laboratory, Red Deer Regional Hospital Centre, Red Deer, Alberta, Canada
ABSTRACT-We report a case of intestinal metaplasia and dysplasia (villous adenoma) of the prostatic urethra secondary to stricture of the prostatic portion of the urethra and chronic inflammation. This sequence of events has previously been recognized in the urothelium of the bladder as a precursor of adenocarcinoma of intestinal type . Premalignant dysplasia of glandular type is rare in the urethra, as is adenocarcinoma, and this case suggests that the pathway to some adenocarcinomas of the urethra may be through intestinal metaplasia and dysplasia similar to the process recognized in the stomach, nose, and urinary bladder.
Intestinal metaplasia is a well-recognized, though rare, occurrence in the mucosa of the urinary tract. It has been described in the renal pelvis, bladder, and urethra 1-4 in relation to stones, chronic infection, exstrophy, urethral stricture, and schistosomiasis and may predispose to adenocarcinoma . 2 & 5 We report a dysplastic and metaplastic intestinal-type villous lesion of the prostate and prostatic urethra in an elderly man secondary to stricture of the urethra and chronic inflammation . Case Report A seventy-five-year-old man presented with increasing difficulty in micturition . He had had a urethral dilatation for stricture at another hospital twenty years earlier following an episode of urethritis many years before . On admission to this hospital cystoscopic examination revealed a long stricture of the membranous and bulbous urethra with mild prostatic enlargement . Urethral dilation was done, and transurethral resection of the prostate yielded 7 .5 g of chippings . The patient was instructed in self-
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catheterization and has been well for two years on that regimen . Pathology Microscopically there was heavy chronic inflammation of the bladder neck and prostatic glands with a few intraglandular microabscesses but without nodular hyperplasia . The urothelial lining of many fragments was normal or infiltrated by neutrophil leukocytes, and there was a heavy chronic inflammatory infiltrate beneath the urothelium . Four of the chippings contained villous metaplasia of intestinal type with Paneth cells, goblet cells, absorptive cells, and argentaffin cells (Fig . IA, B) . The Paneth cells stained for lysozyme (Fig . 1B) and the goblet cells for carcinoembryonic antigen (CEA) . The surrounding prostatic glands were strongly positive for prostate specific antigen, but the intestinal-type lesion was negative . In some areas the intestinal-type lesion was on the surface and in continuity with the urothelium, but in other areas it was in the prostatic stroma, presumably within the major ducts but
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1. (A) Villous metaplastic epithelium containing absorptive and goblet cells shows low-grade dysplasia characterized by nuclear crowding, multilayering, and hyperchromatism analogous with intestinal villous adenomas . (B) Basal Paneth cells stain positively for lysozyme by PAP immunoperoxidase technique . (C) On left side, dysplastic intestinal-type epithelium is on surface ; on right side it involves prostatic glands but does not invade stroma . Uninvolved prostatic glands present on extreme right (arrow), (A and C : hematoxylin and eosin . Original magnifications, x 147, x 294, and x 60, respectively.) FicuRE
adjacent to the ordinary prostatic glands (Fig . IC) . There was no invasion of the underlying prostatic stroma, but the nuclear crowding and hyperchromatism was sufficient to be designated mild-to-moderate dysplasia by analogy with colonic adenomas (Fig . IA, C) . There was some variation in the degree of dysplasia in different areas . Comment Urothelium may undergo intestinal metaplasia under the stimulus of chronic infection, schistosomiasis, calculi, or exstrophy 1-4 Columnar epithelial metaplasia is seen in cystitis glandularis and, when associated with goblet cells only, is designated incomplete intestinal metaplasia,2 whereas when Paneth cells and argentaffin cells are additionally present, it is called complete intestinal metaplasia. I Adenocarcinomas of the urinary bladder are thought to arise either from intestinal metaplasia or from the urachal remnant . 1.3.3 The present case demonstrates that the urothelium lining the prostatic urethra is capable of undergoing metaplasia and dysplasia in the same way as the urothelium of the bladder. 362
A unique villous adenoma of colonic type in the urinary bladder was reported by Assor° and was presumed to arise from cystitis glandularis . It closely resembles the present case . Rare cases of benign villous polyps of the prostatic urethra have also been reported .'-" They are lined by a single layer of tall columnar or cuboidal epithelium devoid of epithelial mucin° and containing prostate specific antigen and prostatic acid phosphatase. 11 Thus they are of prostatic rather than intestinal type . "Endometrioid" carcinoma of the prostatic urethra described by Melicow and Pachter, 13 although first thought to originate from the prostatic utricle (uterus masculinis) because of its morphologic similarity to endometrial carcinoma," ," was shown to be of prostatic origin by histochemistry, electron microscopy, and immunocytochemistry.12. 17 Carcinomas of the urethra are rare . 18-40 The majority are squamous carcinomas, followed in descending order of frequency by transitional cell carcinoma, adenocarcinoma, and undifferentiated carcinoma ." A high proportion of urethral carcinomas are associated with a history of venereal disease, urethral stricture, or
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significant urethral trauma . 18-2 o The premalignant lesions preceding invasive carcinoma are rarely described . Dysplasia was described adjacent to an adenocarcinoma which showed intestinal-type differentiation by electron microscopy but benign metaplasia was not identified ." In other cases urethritis glandularis was associated with stricture, chronic inflammation, and urethral adenocarcinoma .l8,21 This case identifies a new form of villous lesion of the prostatic urethra, an intestinal type, additional to the prostatic form previously recognized and similar to the villous adenoma of the bladder described by Assor .e Furthermore, since it shows dysplasia and resembles villous adenomas of the colon, it is a preinvasive neoplastic lesion . The pathologic sequence of chronic inflammation leading sequentially to metaplasia, dysplasia, and adenocarcinoma is well recognized in the stomach,22 gallbladder, 23 and nose44 but less well in the urinary tract where adenocarcinomas are much less common than transitional cell carcinomas . Nevertheless there is firm literary support for this sequence in the bladder,' ,' and the present case suggests that the same sequence may also occur in the prostatic urethra . Department of Pathology Foothills Hospital Calgary, Alberta, T2N 2T9, Canada (DR . KELLY) References 1 . Gordon M : Intestinal metaplasia of the urinary tract epithelium, j Pathol Bacteriol 85 : 441 (1963) . 2 . Patch FS, and Rhea LJ : The genesis and development of Brunn's nests and their relation to cystitis cystica, cystitis glandularis, and primary adenocarcinoma of the bladder, Can Med Assoc j 33 : 597 (1935) . 3 . Pund ER, Yount HA, and Brunberg JM : Variations in morphology of urinary bladder epithelium . Special reference to cystitis glandularis and carcinoma, j Urol 68 : 242 (1952) . 4 . Ward AM : Glandular neoplama within the urinary tract.
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The etiology of adenocarcinoma of the urothelium with a review of the literature, Virchows Arch [A] 352 : 296 (1971) . 5 . Grace DA, and Winter CC : Mixed differentiation of primary carcinoma of the urinary bladder, Cancer 21 : 1239 (1968) . 6 . Assor D : A villous tumour of the bladder, j Uml 119 : 287 (1978) . 7 . Craig JR, and Hart WR : Benign polyps with prostatic-type epithelium of the urethra, Am J Clin Pathol 63 : 343 (1975) . 8 . Nesbit RM : The genesis of benign polyps in the prostatic urethra, j Urol 87: 416 (1962) . 9 . Murad TM, Robinson LH, and Bueschen AJ : Villous polyps of the urethra: a report of two cases, Human Pathol 10 : 478 (1979) . 10 . Goldstein AMB, Bragin SD, Terry R, and Yoell JH : Prostatic urethral polyps in adults : histopathologic variations and clinical manifestations, J Urol 126 : 129 (1980) . 11 . Remick DG, and Kumar NB : Benign polyps with prostatic-type epithelium of the urethra and the urinary bladder. A suggestion of histogenesis based on histologic and immunohistochemical studies, Am J Surg Pathol 8 : 833 (1984) . 12 . Ellis D W, Leffers S, Davies JS, and Ng ABP : Multiple immunoperoxidase markers in benign hyperplasia and adenocarcinoma of the prostate, Am J Clin Pathol 81 : 279 (1984) . 13 . Melicow MM, and Pachter MR : Endometrioid carcinoma of prostatic utricle (uterus masculinus), Cancer 20 : 1715 (1967) . 14 . Melicow MM, and Tannenbaum M : Endometrial carcinoma of uterus masculinus (prostatic utricle) . Report of 6 cases, j Urol 106 : 892 (1971) . 15 . Nadji M, et al : Prostatic origin of tumors : an immunohistochemical study, Am J Clin Pathol 73 : 735 (1980) . 16 . Walker AN, Mills SE, Fechner RE, and Perry JM : "Endometnioid" adenocarcinoma of the prostatic urethra arising in a villous polyp, a light microscopic and immunoperoxidase study, Arch Pathol Lab Med 106 : 624 (1982) . 17 . Zaloudek C, Williams JW, and Kempson RL : "Endometrial" adenocarcinoma of the prostate, a distinctive tumor of probable prostatic duct origin, Cancer 37 : 2255 (1976) . 18 . Bostwick DG, Lo R, and Stamey TA : Papillary adenocarcinoma of the male urethra : case report and review of the literature, Cancer 54 : 2556 (1984) . 19 . Kaplan GW, Bulkley GJ, and Grayhack JT : Carcinoma of the male urethra, j Urol 98 : 365 (1967) . 20 . Scott EVZ, and Barelare B : Adenocarcinoma of the male urethra, j Urol 68 : 311 (1952) . 21 . Posso MA, Berg CA, Murphy Al, and 7totten RS : Mucinous adenocarcinoma of the urethra : report of a case associated with urethritis glandularis, j Urol 85 : 944 (1961) . 22 . Jarvi 0, and Lauren P : On the role of heterotropias of the intestinal epithelium in the pathogenesis of gastric cancer, Acta Pathol Microblol Scand 29 : 26 (1954) . 23 . Laitio M : Histogenesis of epithelial neoplasms of the human gallbladder, 1 : dysplasia, Pathol Res Pract 178 : 51 (1983) . 24 . Jarvi 0 : A review of the part played by gastrointestinal heterotopias in neoplasmogenesis, Proc Finn Acad Sci Lett . p 151 (1982) .
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ABSTRACT-We report a case of intestinal metaplasia and dysplasia (villous adenoma) of the prostatic urethra secondary to stricture of the prostatic portion of the urethra and chronic inflammation. This sequence of events has previously been recognized in the urothelium of the bladder as a precursor of adenocarcinoma of intestinal type . Premalignant dysplasia of glandular type is rare in the urethra, as is adenocarcinoma, and this case suggests that the pathway to some adenocarcinomas of the urethra may be through intestinal metaplasia and dysplasia similar to the process recognized in the stomach, nose, and urinary bladder.
Intestinal metaplasia is a well-recognized, though rare, occurrence in the mucosa of the urinary tract. It has been described in the renal pelvis, bladder, and urethra 1-4 in relation to stones, chronic infection, exstrophy, urethral stricture, and schistosomiasis and may predispose to adenocarcinoma . 2 & 5 We report a dysplastic and metaplastic intestinal-type villous lesion of the prostate and prostatic urethra in an elderly man secondary to stricture of the urethra and chronic inflammation . Case Report A seventy-five-year-old man presented with increasing difficulty in micturition . He had had a urethral dilatation for stricture at another hospital twenty years earlier following an episode of urethritis many years before . On admission to this hospital cystoscopic examination revealed a long stricture of the membranous and bulbous urethra with mild prostatic enlargement . Urethral dilation was done, and transurethral resection of the prostate yielded 7 .5 g of chippings . The patient was instructed in self-
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catheterization and has been well for two years on that regimen . Pathology Microscopically there was heavy chronic inflammation of the bladder neck and prostatic glands with a few intraglandular microabscesses but without nodular hyperplasia . The urothelial lining of many fragments was normal or infiltrated by neutrophil leukocytes, and there was a heavy chronic inflammatory infiltrate beneath the urothelium . Four of the chippings contained villous metaplasia of intestinal type with Paneth cells, goblet cells, absorptive cells, and argentaffin cells (Fig . IA, B) . The Paneth cells stained for lysozyme (Fig . 1B) and the goblet cells for carcinoembryonic antigen (CEA) . The surrounding prostatic glands were strongly positive for prostate specific antigen, but the intestinal-type lesion was negative . In some areas the intestinal-type lesion was on the surface and in continuity with the urothelium, but in other areas it was in the prostatic stroma, presumably within the major ducts but
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1. (A) Villous metaplastic epithelium containing absorptive and goblet cells shows low-grade dysplasia characterized by nuclear crowding, multilayering, and hyperchromatism analogous with intestinal villous adenomas . (B) Basal Paneth cells stain positively for lysozyme by PAP immunoperoxidase technique . (C) On left side, dysplastic intestinal-type epithelium is on surface ; on right side it involves prostatic glands but does not invade stroma . Uninvolved prostatic glands present on extreme right (arrow), (A and C : hematoxylin and eosin . Original magnifications, x 147, x 294, and x 60, respectively.) FicuRE
adjacent to the ordinary prostatic glands (Fig . IC) . There was no invasion of the underlying prostatic stroma, but the nuclear crowding and hyperchromatism was sufficient to be designated mild-to-moderate dysplasia by analogy with colonic adenomas (Fig . IA, C) . There was some variation in the degree of dysplasia in different areas . Comment Urothelium may undergo intestinal metaplasia under the stimulus of chronic infection, schistosomiasis, calculi, or exstrophy 1-4 Columnar epithelial metaplasia is seen in cystitis glandularis and, when associated with goblet cells only, is designated incomplete intestinal metaplasia,2 whereas when Paneth cells and argentaffin cells are additionally present, it is called complete intestinal metaplasia. I Adenocarcinomas of the urinary bladder are thought to arise either from intestinal metaplasia or from the urachal remnant . 1.3.3 The present case demonstrates that the urothelium lining the prostatic urethra is capable of undergoing metaplasia and dysplasia in the same way as the urothelium of the bladder. 362
A unique villous adenoma of colonic type in the urinary bladder was reported by Assor° and was presumed to arise from cystitis glandularis . It closely resembles the present case . Rare cases of benign villous polyps of the prostatic urethra have also been reported .'-" They are lined by a single layer of tall columnar or cuboidal epithelium devoid of epithelial mucin° and containing prostate specific antigen and prostatic acid phosphatase. 11 Thus they are of prostatic rather than intestinal type . "Endometrioid" carcinoma of the prostatic urethra described by Melicow and Pachter, 13 although first thought to originate from the prostatic utricle (uterus masculinis) because of its morphologic similarity to endometrial carcinoma," ," was shown to be of prostatic origin by histochemistry, electron microscopy, and immunocytochemistry.12. 17 Carcinomas of the urethra are rare . 18-40 The majority are squamous carcinomas, followed in descending order of frequency by transitional cell carcinoma, adenocarcinoma, and undifferentiated carcinoma ." A high proportion of urethral carcinomas are associated with a history of venereal disease, urethral stricture, or
UROLOGY
/
OCTOBER
1988
/
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XXXII,
NUMBER
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significant urethral trauma . 18-2 o The premalignant lesions preceding invasive carcinoma are rarely described . Dysplasia was described adjacent to an adenocarcinoma which showed intestinal-type differentiation by electron microscopy but benign metaplasia was not identified ." In other cases urethritis glandularis was associated with stricture, chronic inflammation, and urethral adenocarcinoma .l8,21 This case identifies a new form of villous lesion of the prostatic urethra, an intestinal type, additional to the prostatic form previously recognized and similar to the villous adenoma of the bladder described by Assor .e Furthermore, since it shows dysplasia and resembles villous adenomas of the colon, it is a preinvasive neoplastic lesion . The pathologic sequence of chronic inflammation leading sequentially to metaplasia, dysplasia, and adenocarcinoma is well recognized in the stomach,22 gallbladder, 23 and nose44 but less well in the urinary tract where adenocarcinomas are much less common than transitional cell carcinomas . Nevertheless there is firm literary support for this sequence in the bladder,' ,' and the present case suggests that the same sequence may also occur in the prostatic urethra . Department of Pathology Foothills Hospital Calgary, Alberta, T2N 2T9, Canada (DR . KELLY) References 1 . Gordon M : Intestinal metaplasia of the urinary tract epithelium, j Pathol Bacteriol 85 : 441 (1963) . 2 . Patch FS, and Rhea LJ : The genesis and development of Brunn's nests and their relation to cystitis cystica, cystitis glandularis, and primary adenocarcinoma of the bladder, Can Med Assoc j 33 : 597 (1935) . 3 . Pund ER, Yount HA, and Brunberg JM : Variations in morphology of urinary bladder epithelium . Special reference to cystitis glandularis and carcinoma, j Urol 68 : 242 (1952) . 4 . Ward AM : Glandular neoplama within the urinary tract.
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The etiology of adenocarcinoma of the urothelium with a review of the literature, Virchows Arch [A] 352 : 296 (1971) . 5 . Grace DA, and Winter CC : Mixed differentiation of primary carcinoma of the urinary bladder, Cancer 21 : 1239 (1968) . 6 . Assor D : A villous tumour of the bladder, j Uml 119 : 287 (1978) . 7 . Craig JR, and Hart WR : Benign polyps with prostatic-type epithelium of the urethra, Am J Clin Pathol 63 : 343 (1975) . 8 . Nesbit RM : The genesis of benign polyps in the prostatic urethra, j Urol 87: 416 (1962) . 9 . Murad TM, Robinson LH, and Bueschen AJ : Villous polyps of the urethra: a report of two cases, Human Pathol 10 : 478 (1979) . 10 . Goldstein AMB, Bragin SD, Terry R, and Yoell JH : Prostatic urethral polyps in adults : histopathologic variations and clinical manifestations, J Urol 126 : 129 (1980) . 11 . Remick DG, and Kumar NB : Benign polyps with prostatic-type epithelium of the urethra and the urinary bladder. A suggestion of histogenesis based on histologic and immunohistochemical studies, Am J Surg Pathol 8 : 833 (1984) . 12 . Ellis D W, Leffers S, Davies JS, and Ng ABP : Multiple immunoperoxidase markers in benign hyperplasia and adenocarcinoma of the prostate, Am J Clin Pathol 81 : 279 (1984) . 13 . Melicow MM, and Pachter MR : Endometrioid carcinoma of prostatic utricle (uterus masculinus), Cancer 20 : 1715 (1967) . 14 . Melicow MM, and Tannenbaum M : Endometrial carcinoma of uterus masculinus (prostatic utricle) . Report of 6 cases, j Urol 106 : 892 (1971) . 15 . Nadji M, et al : Prostatic origin of tumors : an immunohistochemical study, Am J Clin Pathol 73 : 735 (1980) . 16 . Walker AN, Mills SE, Fechner RE, and Perry JM : "Endometnioid" adenocarcinoma of the prostatic urethra arising in a villous polyp, a light microscopic and immunoperoxidase study, Arch Pathol Lab Med 106 : 624 (1982) . 17 . Zaloudek C, Williams JW, and Kempson RL : "Endometrial" adenocarcinoma of the prostate, a distinctive tumor of probable prostatic duct origin, Cancer 37 : 2255 (1976) . 18 . Bostwick DG, Lo R, and Stamey TA : Papillary adenocarcinoma of the male urethra : case report and review of the literature, Cancer 54 : 2556 (1984) . 19 . Kaplan GW, Bulkley GJ, and Grayhack JT : Carcinoma of the male urethra, j Urol 98 : 365 (1967) . 20 . Scott EVZ, and Barelare B : Adenocarcinoma of the male urethra, j Urol 68 : 311 (1952) . 21 . Posso MA, Berg CA, Murphy Al, and 7totten RS : Mucinous adenocarcinoma of the urethra : report of a case associated with urethritis glandularis, j Urol 85 : 944 (1961) . 22 . Jarvi 0, and Lauren P : On the role of heterotropias of the intestinal epithelium in the pathogenesis of gastric cancer, Acta Pathol Microblol Scand 29 : 26 (1954) . 23 . Laitio M : Histogenesis of epithelial neoplasms of the human gallbladder, 1 : dysplasia, Pathol Res Pract 178 : 51 (1983) . 24 . Jarvi 0 : A review of the part played by gastrointestinal heterotopias in neoplasmogenesis, Proc Finn Acad Sci Lett . p 151 (1982) .
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