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Cystitis Follicularis1
CYSTITIS FOLLICULARIS 1 BENJ. H. SCHLOMOVITZ From the Veterans Administrations Facility, Wood, Wis.
The various types of chronic proliferative or hyperplastic lesions of the urinary bladder have been described recently by Hinman and Cordonnier, and Stirling and Ash. It is believed that Cruveilhier was the first to describe this condition in his treatise on pathological anatomy in 1856. There seemed to be a general opinion that the type known as cystitis follicularis or papular cystitis (disseminated lymphoid follicles in the mucosa) was a common finding. Very few cases, however, have been reported since 1881 when Weichselbaum and Chiari differed radically as to its pathologic significance. Przewoski formulated the view which has been generally accepted: the papules or lymphoid nodules are inflammatory in origin, in a large majority of cases. Confirmatory of this opinion are the findings of chronic bacilluria with the colon bacillus as the most frequent offender. In our routine gross inspection of several thousand urinary bladders at autopsy we have seen cystitis follicularis very rarely. This was confirmed by later histologic examination of many bladders including those having changes characteristic of chronic cystitis. It is recognized readily and it is obvious that the urologists, who see many more bladders than either the pathologist or surgeon, could easily discover it by cystoscopic examination, but Hinman and others still report this condition as rare. The cystoscopic findings are characteristic: numerous, discrete, gray, opaque, solid-looking nodules or papules several mm. in diameter stud the mucosa of the urinary bladder and project 1.0 to 3.0 mm. above the surrounding epithelium. Our microscopic examination of the mucosa of bladders (whether normal or pathologic) removed at autopsy never showed collections of lymphoid tissue except in the case reported below. Textbooks on histology still state that the mucosa of the urinary bladder sometimes contains small lymphatic nodules, but our experience finds this to be true of only pathologically altered mucosa. Although Hinman states that "no follicles have been found in the urinary tract of the newborn," still the fact that the urinary bladder and rectum are both derived embryologically from the cloaca, makes it possible that rarely an individual may show occasional discrete lymphoid follicles in the bladder mucosa. This rare "normal" discrete condition is far different, however, from cystitis follicularis in which the mucosa is peppered with follicles. The case which is the subject of this report had the following medical history. At the age of 22 he had a gonorrheal urethritis; at 35 a tonsillectomy and appendectomy. At 35, his gall-bladder was removed because of a chronic cholecysitis; a right nephroptosis was repaired and at this time the kidney was found to be hydronephrotic; and later he was treated medically for a trigonitis and 1 Published by authority of the Medical Director, Veterans Administration, Washington, D. C., who assumes no responsibility for opinions expressed by the author. 168
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Vincent's angina. At 42, he had attacks of severe pain in the left loin and a perinephric abscess on the left side was drained. A diagnosis of left pyelo-. nephritis was made. Later the right kidney was removed because of calculi, and we reported the specimen as "pyonephrosis with stones." X-ray examination at that time did not reveal calculi in the left kidney. In May 1941, when he was 43 years old, exitus occurred from acute dilatation of the heart on the basis of a toxic myocarditis with congestive heart failure. His blood Wassermann and Kahn tests were negative repeatedly during the last 7 years of his life. His blood pressure was normal throughout the same period. No urethral obstruction was discovered clinically. He had no diarrhoea. The post-mortem findings were as follows: pathologic changes of congestive heart failure (edema, congestion and transudates); enlargement of the lymph nodes that drained the renal areas; extensive postoperative abdominal adhesions; dense peritoneum; early septic spleen; toxic hepatitis; pallor of secondary anemia; and recent extensive, chronic adhesive pleurisy on the left side. The urinary tract disclosed a dense fibrosis at the site from which the right kidney had been removed; calculi in a chronic left pyelonephritis and hydronephrosis with fistulae extending from the left perinephric space into the adjacent iliopsoas muscles; thick greenish pus filled the kidney pelvis, ureter and fistulae; the left adrenal gland was encased by dense fibrotic tissue; subacute ureteritis; chronic follicular cystitis; urinary bladder distended by 500 cc of a greenish-gray turbid urine; and chronic prostatitis. Histologic examination of the kidney disclosed the findings typical of pyelonephritis and hydronephrosis. Microscopic examination of the epithelial layer lining the pelvis of the kidney, ureter, urinary bladder, posterior prostatic urethra and prostatic tubuloalveolar glands showed a generalized infiltration with lymphocytes and mononuclears (chronic inflammatory cells) and a generalized capillary injection throughout. Careful scrutiny disclosed ovoid lymphoid collections in the superficial portions of the epithelial layer nowhere except in the urinary bladder. In the bladder the lymphoid collections were usually centrally placed in the papules or nodules that projected above the surrounding plateau of epithelium or mucosa. An intact epithelium forms the free surface of the papule. A naked eye inspection of the histologic sections shows that the lymphoid tissue occupies approximately ½to ½of the total area of the papule. The remainder of the papule is composed of a loose, fine connective tissue background relatively acellular, and containing large blood-vessels and lymphatic vessels usually located at the periphery of the papule. No small blood vessels or sinuses could be visualized in the lymphocytic collections. The lymphoid collections contained no secondary follicles or germinal centers and no mitotic figures were discovered. In the state of our present knowledge on the significance of the secondary follicles in infections and toxic conditions and the controversy about the cyclic phases occurring in the germinal centers, it would be a waste of time to engage in an extended discussion. On the one hand it is stated that secondary follicles
'170
BENJ. H. SCHLOMOVITZ
may disappear in various chronic ailments and that in highly active lymphoid tissue, they tend to be replaced or crowded out by lymphocytes. On the other hand "in the stage of complete rest the secondary nodule is quite inconspicuous." It is a curious fact, in the case reported above, that although a histologically similar epithelial layer lined the urinary tract from the renal pelvis down to the prostate and showed evidence of an inflammatory reaction throughout, the lymphoid papules were found only in the urinary bladder. Clincally, it is known that there are no distinguishing symptoms peculiar to cystitis follicularis. The complaints may be such as are found in any chronic inflammation of the bladder, or at times the patient may be entirely free of symptoms. SUMMARY
At autopsy the case reported above disclosed an extensive, generalized lymphoid nodular involvement of the mucosa only in the urinary gladder, although there was a widespread inflammatory condition of the mucosa lining the excretory passageway of the entire urinary tract and glands of the prostate.
1210 Majestic Bldg., Milwaukee, Wis. REFERENCES BAETZNER, W.: Beitrag zur Kenntnis der Pyelitis granulosa. Ztschr. f. urol. Chir., 1: 285, 1913. CHIARI, H.: Med. Jahrb., 1881, 9. HINMAN, FRANK: Principles and Practice of Urology. Philadelphia and London: W. B. Saunders Co., 1935. ---AND CoRDONNIER, JusTIN: Cystitis follicularis. J. Urol., 34: 320, 1935. KRETSCHMER, H. L.: Pyelitis follicularis. Trans. Am. Urol. Assoc., 7: 94, 1913. MAXIMOW, ALEXANDER A., AND BLOOM, WILLIAM: In: Special Cytology; E. V. Cowdry, editor. 2: 603-643, 1932. - - - AND BLOOM, WILLIAM: Textbook of Histology, Philadelphia and London: W. B. Saunders Co., 1935. PRZEWOSKI, E.: Ueber nodulare oder folliculare Entzundung der Schleimhaut der Harnwege. Virchow's Arch., 116: 516, 1889. STIRLING, W. C.: Cystitis follicularis. J. A. M.A., 112: 1326, 1939. - - - AND AsH, J. E.: Chronic proliferative lesions of urinary tract. J. Urol., 45: 342, 1941. ---AND AsH, J.E.: A clinico-pathologic discussion of hyperplastic lesions of urinary tract. South M. J., 34: 358, 1941. WEICHSELBAUM, A.: Ueber das Vorkommen lymphatischen Gewebes in der normaler Harnblasenschleimhaut des Menschen. Allg. Wiener Med. Ztg., 26: 346, 1881.
The various types of chronic proliferative or hyperplastic lesions of the urinary bladder have been described recently by Hinman and Cordonnier, and Stirling and Ash. It is believed that Cruveilhier was the first to describe this condition in his treatise on pathological anatomy in 1856. There seemed to be a general opinion that the type known as cystitis follicularis or papular cystitis (disseminated lymphoid follicles in the mucosa) was a common finding. Very few cases, however, have been reported since 1881 when Weichselbaum and Chiari differed radically as to its pathologic significance. Przewoski formulated the view which has been generally accepted: the papules or lymphoid nodules are inflammatory in origin, in a large majority of cases. Confirmatory of this opinion are the findings of chronic bacilluria with the colon bacillus as the most frequent offender. In our routine gross inspection of several thousand urinary bladders at autopsy we have seen cystitis follicularis very rarely. This was confirmed by later histologic examination of many bladders including those having changes characteristic of chronic cystitis. It is recognized readily and it is obvious that the urologists, who see many more bladders than either the pathologist or surgeon, could easily discover it by cystoscopic examination, but Hinman and others still report this condition as rare. The cystoscopic findings are characteristic: numerous, discrete, gray, opaque, solid-looking nodules or papules several mm. in diameter stud the mucosa of the urinary bladder and project 1.0 to 3.0 mm. above the surrounding epithelium. Our microscopic examination of the mucosa of bladders (whether normal or pathologic) removed at autopsy never showed collections of lymphoid tissue except in the case reported below. Textbooks on histology still state that the mucosa of the urinary bladder sometimes contains small lymphatic nodules, but our experience finds this to be true of only pathologically altered mucosa. Although Hinman states that "no follicles have been found in the urinary tract of the newborn," still the fact that the urinary bladder and rectum are both derived embryologically from the cloaca, makes it possible that rarely an individual may show occasional discrete lymphoid follicles in the bladder mucosa. This rare "normal" discrete condition is far different, however, from cystitis follicularis in which the mucosa is peppered with follicles. The case which is the subject of this report had the following medical history. At the age of 22 he had a gonorrheal urethritis; at 35 a tonsillectomy and appendectomy. At 35, his gall-bladder was removed because of a chronic cholecysitis; a right nephroptosis was repaired and at this time the kidney was found to be hydronephrotic; and later he was treated medically for a trigonitis and 1 Published by authority of the Medical Director, Veterans Administration, Washington, D. C., who assumes no responsibility for opinions expressed by the author. 168
CYSTITIS FOLLICULARIS
169
Vincent's angina. At 42, he had attacks of severe pain in the left loin and a perinephric abscess on the left side was drained. A diagnosis of left pyelo-. nephritis was made. Later the right kidney was removed because of calculi, and we reported the specimen as "pyonephrosis with stones." X-ray examination at that time did not reveal calculi in the left kidney. In May 1941, when he was 43 years old, exitus occurred from acute dilatation of the heart on the basis of a toxic myocarditis with congestive heart failure. His blood Wassermann and Kahn tests were negative repeatedly during the last 7 years of his life. His blood pressure was normal throughout the same period. No urethral obstruction was discovered clinically. He had no diarrhoea. The post-mortem findings were as follows: pathologic changes of congestive heart failure (edema, congestion and transudates); enlargement of the lymph nodes that drained the renal areas; extensive postoperative abdominal adhesions; dense peritoneum; early septic spleen; toxic hepatitis; pallor of secondary anemia; and recent extensive, chronic adhesive pleurisy on the left side. The urinary tract disclosed a dense fibrosis at the site from which the right kidney had been removed; calculi in a chronic left pyelonephritis and hydronephrosis with fistulae extending from the left perinephric space into the adjacent iliopsoas muscles; thick greenish pus filled the kidney pelvis, ureter and fistulae; the left adrenal gland was encased by dense fibrotic tissue; subacute ureteritis; chronic follicular cystitis; urinary bladder distended by 500 cc of a greenish-gray turbid urine; and chronic prostatitis. Histologic examination of the kidney disclosed the findings typical of pyelonephritis and hydronephrosis. Microscopic examination of the epithelial layer lining the pelvis of the kidney, ureter, urinary bladder, posterior prostatic urethra and prostatic tubuloalveolar glands showed a generalized infiltration with lymphocytes and mononuclears (chronic inflammatory cells) and a generalized capillary injection throughout. Careful scrutiny disclosed ovoid lymphoid collections in the superficial portions of the epithelial layer nowhere except in the urinary bladder. In the bladder the lymphoid collections were usually centrally placed in the papules or nodules that projected above the surrounding plateau of epithelium or mucosa. An intact epithelium forms the free surface of the papule. A naked eye inspection of the histologic sections shows that the lymphoid tissue occupies approximately ½to ½of the total area of the papule. The remainder of the papule is composed of a loose, fine connective tissue background relatively acellular, and containing large blood-vessels and lymphatic vessels usually located at the periphery of the papule. No small blood vessels or sinuses could be visualized in the lymphocytic collections. The lymphoid collections contained no secondary follicles or germinal centers and no mitotic figures were discovered. In the state of our present knowledge on the significance of the secondary follicles in infections and toxic conditions and the controversy about the cyclic phases occurring in the germinal centers, it would be a waste of time to engage in an extended discussion. On the one hand it is stated that secondary follicles
'170
BENJ. H. SCHLOMOVITZ
may disappear in various chronic ailments and that in highly active lymphoid tissue, they tend to be replaced or crowded out by lymphocytes. On the other hand "in the stage of complete rest the secondary nodule is quite inconspicuous." It is a curious fact, in the case reported above, that although a histologically similar epithelial layer lined the urinary tract from the renal pelvis down to the prostate and showed evidence of an inflammatory reaction throughout, the lymphoid papules were found only in the urinary bladder. Clincally, it is known that there are no distinguishing symptoms peculiar to cystitis follicularis. The complaints may be such as are found in any chronic inflammation of the bladder, or at times the patient may be entirely free of symptoms. SUMMARY
At autopsy the case reported above disclosed an extensive, generalized lymphoid nodular involvement of the mucosa only in the urinary gladder, although there was a widespread inflammatory condition of the mucosa lining the excretory passageway of the entire urinary tract and glands of the prostate.
1210 Majestic Bldg., Milwaukee, Wis. REFERENCES BAETZNER, W.: Beitrag zur Kenntnis der Pyelitis granulosa. Ztschr. f. urol. Chir., 1: 285, 1913. CHIARI, H.: Med. Jahrb., 1881, 9. HINMAN, FRANK: Principles and Practice of Urology. Philadelphia and London: W. B. Saunders Co., 1935. ---AND CoRDONNIER, JusTIN: Cystitis follicularis. J. Urol., 34: 320, 1935. KRETSCHMER, H. L.: Pyelitis follicularis. Trans. Am. Urol. Assoc., 7: 94, 1913. MAXIMOW, ALEXANDER A., AND BLOOM, WILLIAM: In: Special Cytology; E. V. Cowdry, editor. 2: 603-643, 1932. - - - AND BLOOM, WILLIAM: Textbook of Histology, Philadelphia and London: W. B. Saunders Co., 1935. PRZEWOSKI, E.: Ueber nodulare oder folliculare Entzundung der Schleimhaut der Harnwege. Virchow's Arch., 116: 516, 1889. STIRLING, W. C.: Cystitis follicularis. J. A. M.A., 112: 1326, 1939. - - - AND AsH, J. E.: Chronic proliferative lesions of urinary tract. J. Urol., 45: 342, 1941. ---AND AsH, J.E.: A clinico-pathologic discussion of hyperplastic lesions of urinary tract. South M. J., 34: 358, 1941. WEICHSELBAUM, A.: Ueber das Vorkommen lymphatischen Gewebes in der normaler Harnblasenschleimhaut des Menschen. Allg. Wiener Med. Ztg., 26: 346, 1881.