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Malakoplakia of the Urinary Bladder and Generalized Sarcoidosis, Striking Similarity of Their Pathology, Etiology, Gross Appearance and Methods of Treatment1
MALAKOPLAKIA OF THE URINARY BLADDER AND GENERALIZED SARCOIDOSIS, STRIKING SIMILARITY OF THEIR PATHOLOGY, ETIOLOGY, GROSS APPEARANCE AND METHODS OF TREATMENT1 FRANCIS H. REDEWILL
Just as Schaumann2 in 1914 showed that Besnier's lupus pernio 3 of the nose, ears and fingers and Boeck's sarcoid4 of the skin, mucous membrane and lymph nodes are the same disease, so I will here attempt to point out how malakoplakia is strikingly similar to this complicated condition known today as sarcoidosis. Malakoplakia, was named by von Hansemann 5 in 1906, but was first described by Michaels and Gutmann6 in 1903. Since then there have been several excellent German articles describing this condition of the urinary bladder, of which one of the best is by Oppermann 7 • An excellent description of this lesion with colored plates is that by McDonald and Sewell 8 published in Great Britain. The first American article on the subject was by Pappenheimer 9 • Malakoplakia means soft plaques; the condition is characterized by brownish raised areas of the mucous membrane of the bladder; it also occurs in the kidney pelvis and ureters, the size of the plaques varies from pinhead single nodules to large coalesced masses with a spread of from 3 to 5 cm. and raised from 1 to 2 cm. above the normal mucous membrane (fig. 1). These growths are soft and have a tendency to central umbilication. Oppermann has reported 40 cases of malakoplakia, 28 in women, including one in a girl of 8 and 12 in men, almost all of them being past 40 years of age. There have been 3 cases reported in children. This condition may exist in the bladder for years without producing symptoms. Indeed, many authorities believe that it is far more common than reported because few make routine systematic urologic examinations of the symptomless urinary tract. Kimila10 in 1906 showed that tuberculous changes of the vesical 1 Read at the twentieth annual convention of the Western Section, the American Urological Association, Del Monte, Calif., June 22, 1942. 2 Schaumann, J.: Benign lymphogranuloma and Its cutaneous manifestations, Brit. J. Dermat., 36: 515, 1924; Congres international de dermatologie, Copenhagen; Lymphogranulomatosis benigna in the light of prolonged clinical observations and autopsy findings. Brit. J. Dermat., 48: 399, 1936; Sur le lupus pernio: Memoire presente en Novembre, 1914 a la Societe francaise de dermatologie et de syphiligraphic pour le Prix Zambaco. 'Besnier, E.: Lupus pernio de la face: synovites funguences symetrique des extremites superieures, Ann. de dermat. et syph., 10: 333, 1889. 4 Boeck, C.: Multiple benign sarcoid of skin; J. Cutan. & Genito-Urin. Dis., 17: 543,
1899. 5 Redewill, F. H.: Comparison of leukoplakia, malakoplakia and incrusted cystitis. J. A. M.A., 92: 532-536, 1929. von Hausemann and Hart: Ueber Malakoplakia der Harnblase. Virchows Arch. f. path. Anat., 173: 302, 1903. 6 Michaelis and Gutmann: Ueber Einschlusse in Blasentumoren. Ztschr. f. klin. Med., 47: 208, 1902. 7 Oppermann, E.: Malakoplakia of the urinary bladder in a girl of eight years; Ztschr. f. Urol., 38: 365, 1926. 8 McDonald, Stewart and Sewell, W. T.: Malakoplakia of the bladder and kidneys. J. Path. and Bact., 18: 306, 1913, 1914. . . 9 Pappenheimer: Malakoplakia of the urinary bladder: Report of two cases, New York Path. Soc., 1906. 1 ° Kimla: Hausemann's Malakoplakia vesica urinariae und ihre Bezieh.ung zur plaqueformigen. Tubrculese der Harnblase. Virchous Arch. f. path. Anat., 184: 469, 1906.
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FRANCIS H. REDEWILL
membrane can offer microscopically a picture which answers that of malakoplakia; whereas in 28 out of 40 of Oppermann's cases a diagnosis of tuberculosis had been made, in 12 no tuberculous involvement could be found postmortem. The reactivity to tuberculin in very low, even less than that of apparently non-
FIG. 1. Diagrammatic sketch of Case 2. plaques above interureteric ridge.
FIG. 2. A sarcoid of right cheek
Urinary bladder depicting malakoplakia
FIG. 3. Sarcoidosis of arm near elbow
tuberculous controls. It is interesting to note that no positive tuberculous cultures could be grown from malakoplakia plaques by any of the investigators, and Guterbock11 , Loth12 and Oppermann could find no bacteria in the tissues. Guterbock: Ein Pertraggur Malakoplakie der Harnblase, Diss. Leipzig, 1905. Loth: Ueber Zwei besonders saltene Falle Von Harnblasen Affektion. Monatsk f. Ural., 11: 90, 1906. 11
12
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The literature on sarcoidosis has reached enormous proportions partly because the disease appears in a variety of recognized forms. Many reviews and discussions on the relationship of sarcoid to tuberculosis, its etiology, pathoegnesis, treatment and manner by which recovery ensues have been described by Pautrier13, Rissmeyer14 , Schaumann, Longcope and Pierson15 , contributors to the Reunion Dermatologique 193416, Pinner17 , Snapper18 and Hunter19. The latest contribution by Longcope and Pierson20 presents observations made on 33 new cases. The age of patients in this group varied from 10 to 51. Sarcoid presents the features of chronic granuloma which seldom produces serious constitutional symptoms but persists for years. The predilection of the sarcoid is for the skin, consisting of certain nodular grouped superficial and subcutaneous granulmatous -infiltrations with a more or less tuberculous histology
Frn. 4. Sarcoidosis of back with extensive plaques
(figs. 2, 3, 4). The lesions are of a dull tint, being red, purple or brown plaques, having a tendency to umbilication. In more than half the cases sarcoids invade the mucous membranes, in which cases they are naturally softer than those that are pushed up through the tough integument of the epidermis. The superficial type of sarcoid is known as the Boeck, whereas the deep is called DornierRoussey21 from the authors who first described them. 13 Pautrier, L. M.: Une nouvelle grande reticulo-endotheliose Maladie de Besnier_Boeck-Schaumann Paris, Messon & Cie, 1940; Nouvelles remarques sur la maladie de Besnier-Boeck-Schumann Syndrome de Heerfordt, Bull, et mem. Soc. med. des hop. de Paris, 64: 708, 1938. 14 Rissmeyer, A.: La maladie Boeck: Sarcoides cutanees benignes multiples, Copenhagen, Levin & Munksgaard, 1932. 16 Longcope, W. T., and Pierson, J. W.: Boeck's sarcoid. Bull. John Hopkins Hosp., 60: 223, 1937. 16 Reunion Dermtologique, 1934. 11 Pinner, M.: Noncaseating Tuberculosis, A. Rev. Tuber., 37: 690, 1938. 1s Snapper, I., and Pompen, A. W. M.: Pseudotuberculosis in man. Lectures given in November 1937 at the Univ. of London, Haarlem, Deerven F. Bohn, 1938. 1 9 Hunter, F. T.: Hutchinson-Boeck's disease (generalized sarcoidosis). New England J.Med.,214:346, 1936. 20 Longcope, W. T., and Pierson, J. W.: Sarcoidosis or Besnier-Boeck-Schumann Disease, J. A. M.A., 117: 1321, 1941. 21 Dornier-Roussey: Ein Fall von Hautsarkoiden mit identischen Veranderungen. Arch. and Dermat. Sypth., 161: 504, 1930.
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FRANCIS H. REDEWILL
As Longcope, et al. say, "in the study of patients -with sarcoid, one is impressed by the fact that symptoms, when they exist, are caused primarily by the mechanical interference with the function of organs rather than by any form of intoxication." Massive involvement of the eye may necessitate enucleation, whereas extensive growth in the musculature of the heart, mediastinum and lungs may produce severe dyspnea and even death. This is due to mechanical interference with these organs and not to infection. It is interesting to note that most of these cases, even with massive involvement, will clear up with no signs of sarcoidosis, although recurrence is not uncommon, and the disease is likely to run a long course, during which relapses with involvement of different organs and tissues alternate with quiescent and latent periods. Sarcoids have been described as occurring in all parts of the body, including the urinary tract, though we could find in the literature no detailed description of their appearance in the urinary bladder, while, on the other hand, malakoplakia of the bladder has been described by hosts of writers. Longcope and Pierson have described symptomless involvement of the urinary tract with the former, though no detailed description is given. GROSS APPEARANCE
Various authors have described malakoplakia of the bladder as raised nodules, involving the trigone and adjacent areas at the base of the bladder, varying in size from 0.5 cm to several centimeters in diameter. Some of the masses are rounded and almost pedunculated, others have broad bases and resemble plaques. None of these growths in the bladder had the appearance of papillomata, there being no fronds or villi. None showed ulceration but many of the larger ones are often umbilicated. MICROSCOPIC APPEARANCE
JVI alakoplakia. The appearance may strongly suggest tuberculosis, being distinguished by lack of caseation, exudation and calcification. Histologic examination of the nodules reveals collections of large, palely staining epithelioid cells arranged in the form of miliary tubercles, sometimes as isolated structures in comparatively normal tissue, and sometimes occurring in groups or strands. Giant cells are numerous, surrounded by outpouring of epithelioid cells and connective tissue stroma containing spindle cells (figs. 5, 6). Over 15 years ago I described the calcium-like inclusion bodies in the giant cells of malakoplakia tissue (5); this has been considered pathognomonic of this tissue. Sarcoids. Here the histologic picture also strongly suggests tuberculosis with lack of caseation, exudation or calcification. Giant cells are present as well as large epithelioid cells surrounded by connective tissue. Tumors of both types have a tendency to umbilicate but in neither type do they break down and ulcerate. Giant cells of sarcoids are often extremely large and irregular, showing many pale nuclei and containing peculiar inclusions of various sizes and shapes staining deeply in hematoxylin. These cell inclusions, repeatedly observed, give the appearance of calcified material. These inclusions have been repeatedly
MALAKOPLAKIA OF URINARY BLADDER AND SARCOIDOSIS
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reported as pathognomonic of malakoplakia. In both malakoplakia and sarcoid the reaction to tuberculin is very low. The globulin fraction of plasma proteins is markedly increased in both malakoplakia and sarcoidosis, depending directly on the amount of this foreign tissue present.
Frn. 5. Photomicrograph of skin sarcoid. giant cells with calcified inclusion bodies.
K ote epitheloid cells and extremely large
Frn. 6. Photomicrograph of biopsy specimen of malakoplakia, Case 2. and giant cells with inclusion bodies.
K oted epitheloid
CASE REPORTS
Case 1. No. 582, male, J. S., age 62, with hematuria but without symptoms of cystitis, was examined in June 1927, and found to have chronic pulmonary tuberculosis in the primary stage in the upper right lobe, chronic arthritis and hypertrophied prostate. There were albumin and casts in the urine but bacteria
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FRANCIS H. REDEWILL
were not demonstrable after continued search. There was no frequency, tenesmus or residual urine and pyelograms taken on each side showed the pelves to be negative as to pathologic signs. Four lavages of the kidney pelves with weak silver nitrate solution cleared up the hematuria. There were numerous raised, rounded, brownish soft plaques, varying in size from that of a pea to one coalesced nodule in the upper right portion of the bladder wall with about a 3 cm. spread. The plaques did not show ulceration. Upon removal of a small plaque with cystoscopic ronguer frozen sections showed typical malakoplakia cells with large epithelial cells. A diagnosis of malakoplakia of the urinary bladder was made. The patient was treated for four months. Some of the nodules disappeared and the remainder decreased in size. Case 2. No. 2256, a woman, M. L., aged 40, fell 1 week before from a street car. She came in on November 1941 complaining of pain in the right back, radiating around to the front and blood in the urine. Physical examination revealed brownish soft plaques distributed over the body, especially on the elbows, arms, chest and back and also two large ones on the sides of her cheeks. This condition which developed gradually over 1 year was symptomless. Diagnosis, generalized sarcoidosis and partial rupture of the right kidney as result of fall. Cystoscopy revealed sanguinous urine being expelled from the right ureter. There were no signs of internal hemorrhage, the patient was in fairly good shape. Treated expectantly, the condition cleared up. On examining the bladder I found brownish soft plaques above the interureteric ridge which I diagnosed as malakoplakia. I was struck by the similarity of the plaques on the surface of the body with the malakoplakia of the bladder. I induced the patient to allow me to make a biopsy of several sarcoids and also of the malakoplakia. Stained sections of both types revealed strikingly similar pathological changes. Below the mucous membrane, on the one hand and cutis on the other, I found a dissemination of giant cells with outpouring of large epithelioid cells surrounded by connective tissue stroma, spindle shaped cells, and calcified-like inclusions in the giant cells. ·wny cannot this so-called malakoplakia be a form of sarcoid? Many articles have been written on both of these conditions. However, no one has associated the one with the other. Let me summarize how closely related these two conditions are. SUMMARY
If it were possible to transplant malakoplakia of the bladder to the skin, lymph nodes or any other part of the body, it would be diagnosed sarcoid. Why? Because the gross and microscopic pathology of the former are similar to the latter, including (a) the large epithelioid cells, (b) giant cells with (c) corpus amylaciallike calcium inclusions that are characteristic of both types, (d) unless the growths impinge mechanically in some organ they are symptomless. (e) These symptomless types of both diseases as a rule heal spontaneously; (f) the globulin fraction of the plasma is increased in both types in direct proportion to the size
MALAKOPLAKIA OF URIKARY BLADDER AND SARCOIDOSIS
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and number of tumor masses. (g) The tumors of both types umbilicate, do not ulcerate; tubercle bacteria cannot be cultured from either. (h) There is often a tuberculous diathesis in the patient who harbors either type, though his tuberculin reaction is low. I believe that, if the scores of generalized sarcoidosis cases that have been reported had been cystoscoped, a great many would have been discovered to have so-called malakoplakia of the bladder, that is, bladder sarcoids. I have reported 1 case of generalized sarcoidosis that I found to have malakoplakia of the bladder, the pathology of biopsy specimens of both conditions being strikingly similar. Flood Bldg., San Francisco, Calif.
Just as Schaumann2 in 1914 showed that Besnier's lupus pernio 3 of the nose, ears and fingers and Boeck's sarcoid4 of the skin, mucous membrane and lymph nodes are the same disease, so I will here attempt to point out how malakoplakia is strikingly similar to this complicated condition known today as sarcoidosis. Malakoplakia, was named by von Hansemann 5 in 1906, but was first described by Michaels and Gutmann6 in 1903. Since then there have been several excellent German articles describing this condition of the urinary bladder, of which one of the best is by Oppermann 7 • An excellent description of this lesion with colored plates is that by McDonald and Sewell 8 published in Great Britain. The first American article on the subject was by Pappenheimer 9 • Malakoplakia means soft plaques; the condition is characterized by brownish raised areas of the mucous membrane of the bladder; it also occurs in the kidney pelvis and ureters, the size of the plaques varies from pinhead single nodules to large coalesced masses with a spread of from 3 to 5 cm. and raised from 1 to 2 cm. above the normal mucous membrane (fig. 1). These growths are soft and have a tendency to central umbilication. Oppermann has reported 40 cases of malakoplakia, 28 in women, including one in a girl of 8 and 12 in men, almost all of them being past 40 years of age. There have been 3 cases reported in children. This condition may exist in the bladder for years without producing symptoms. Indeed, many authorities believe that it is far more common than reported because few make routine systematic urologic examinations of the symptomless urinary tract. Kimila10 in 1906 showed that tuberculous changes of the vesical 1 Read at the twentieth annual convention of the Western Section, the American Urological Association, Del Monte, Calif., June 22, 1942. 2 Schaumann, J.: Benign lymphogranuloma and Its cutaneous manifestations, Brit. J. Dermat., 36: 515, 1924; Congres international de dermatologie, Copenhagen; Lymphogranulomatosis benigna in the light of prolonged clinical observations and autopsy findings. Brit. J. Dermat., 48: 399, 1936; Sur le lupus pernio: Memoire presente en Novembre, 1914 a la Societe francaise de dermatologie et de syphiligraphic pour le Prix Zambaco. 'Besnier, E.: Lupus pernio de la face: synovites funguences symetrique des extremites superieures, Ann. de dermat. et syph., 10: 333, 1889. 4 Boeck, C.: Multiple benign sarcoid of skin; J. Cutan. & Genito-Urin. Dis., 17: 543,
1899. 5 Redewill, F. H.: Comparison of leukoplakia, malakoplakia and incrusted cystitis. J. A. M.A., 92: 532-536, 1929. von Hausemann and Hart: Ueber Malakoplakia der Harnblase. Virchows Arch. f. path. Anat., 173: 302, 1903. 6 Michaelis and Gutmann: Ueber Einschlusse in Blasentumoren. Ztschr. f. klin. Med., 47: 208, 1902. 7 Oppermann, E.: Malakoplakia of the urinary bladder in a girl of eight years; Ztschr. f. Urol., 38: 365, 1926. 8 McDonald, Stewart and Sewell, W. T.: Malakoplakia of the bladder and kidneys. J. Path. and Bact., 18: 306, 1913, 1914. . . 9 Pappenheimer: Malakoplakia of the urinary bladder: Report of two cases, New York Path. Soc., 1906. 1 ° Kimla: Hausemann's Malakoplakia vesica urinariae und ihre Bezieh.ung zur plaqueformigen. Tubrculese der Harnblase. Virchous Arch. f. path. Anat., 184: 469, 1906.
401
402
FRANCIS H. REDEWILL
membrane can offer microscopically a picture which answers that of malakoplakia; whereas in 28 out of 40 of Oppermann's cases a diagnosis of tuberculosis had been made, in 12 no tuberculous involvement could be found postmortem. The reactivity to tuberculin in very low, even less than that of apparently non-
FIG. 1. Diagrammatic sketch of Case 2. plaques above interureteric ridge.
FIG. 2. A sarcoid of right cheek
Urinary bladder depicting malakoplakia
FIG. 3. Sarcoidosis of arm near elbow
tuberculous controls. It is interesting to note that no positive tuberculous cultures could be grown from malakoplakia plaques by any of the investigators, and Guterbock11 , Loth12 and Oppermann could find no bacteria in the tissues. Guterbock: Ein Pertraggur Malakoplakie der Harnblase, Diss. Leipzig, 1905. Loth: Ueber Zwei besonders saltene Falle Von Harnblasen Affektion. Monatsk f. Ural., 11: 90, 1906. 11
12
MALAKOPLAKIA OF URINARY BLADDER AND SARCOIDOSIS ·
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The literature on sarcoidosis has reached enormous proportions partly because the disease appears in a variety of recognized forms. Many reviews and discussions on the relationship of sarcoid to tuberculosis, its etiology, pathoegnesis, treatment and manner by which recovery ensues have been described by Pautrier13, Rissmeyer14 , Schaumann, Longcope and Pierson15 , contributors to the Reunion Dermatologique 193416, Pinner17 , Snapper18 and Hunter19. The latest contribution by Longcope and Pierson20 presents observations made on 33 new cases. The age of patients in this group varied from 10 to 51. Sarcoid presents the features of chronic granuloma which seldom produces serious constitutional symptoms but persists for years. The predilection of the sarcoid is for the skin, consisting of certain nodular grouped superficial and subcutaneous granulmatous -infiltrations with a more or less tuberculous histology
Frn. 4. Sarcoidosis of back with extensive plaques
(figs. 2, 3, 4). The lesions are of a dull tint, being red, purple or brown plaques, having a tendency to umbilication. In more than half the cases sarcoids invade the mucous membranes, in which cases they are naturally softer than those that are pushed up through the tough integument of the epidermis. The superficial type of sarcoid is known as the Boeck, whereas the deep is called DornierRoussey21 from the authors who first described them. 13 Pautrier, L. M.: Une nouvelle grande reticulo-endotheliose Maladie de Besnier_Boeck-Schaumann Paris, Messon & Cie, 1940; Nouvelles remarques sur la maladie de Besnier-Boeck-Schumann Syndrome de Heerfordt, Bull, et mem. Soc. med. des hop. de Paris, 64: 708, 1938. 14 Rissmeyer, A.: La maladie Boeck: Sarcoides cutanees benignes multiples, Copenhagen, Levin & Munksgaard, 1932. 16 Longcope, W. T., and Pierson, J. W.: Boeck's sarcoid. Bull. John Hopkins Hosp., 60: 223, 1937. 16 Reunion Dermtologique, 1934. 11 Pinner, M.: Noncaseating Tuberculosis, A. Rev. Tuber., 37: 690, 1938. 1s Snapper, I., and Pompen, A. W. M.: Pseudotuberculosis in man. Lectures given in November 1937 at the Univ. of London, Haarlem, Deerven F. Bohn, 1938. 1 9 Hunter, F. T.: Hutchinson-Boeck's disease (generalized sarcoidosis). New England J.Med.,214:346, 1936. 20 Longcope, W. T., and Pierson, J. W.: Sarcoidosis or Besnier-Boeck-Schumann Disease, J. A. M.A., 117: 1321, 1941. 21 Dornier-Roussey: Ein Fall von Hautsarkoiden mit identischen Veranderungen. Arch. and Dermat. Sypth., 161: 504, 1930.
404
FRANCIS H. REDEWILL
As Longcope, et al. say, "in the study of patients -with sarcoid, one is impressed by the fact that symptoms, when they exist, are caused primarily by the mechanical interference with the function of organs rather than by any form of intoxication." Massive involvement of the eye may necessitate enucleation, whereas extensive growth in the musculature of the heart, mediastinum and lungs may produce severe dyspnea and even death. This is due to mechanical interference with these organs and not to infection. It is interesting to note that most of these cases, even with massive involvement, will clear up with no signs of sarcoidosis, although recurrence is not uncommon, and the disease is likely to run a long course, during which relapses with involvement of different organs and tissues alternate with quiescent and latent periods. Sarcoids have been described as occurring in all parts of the body, including the urinary tract, though we could find in the literature no detailed description of their appearance in the urinary bladder, while, on the other hand, malakoplakia of the bladder has been described by hosts of writers. Longcope and Pierson have described symptomless involvement of the urinary tract with the former, though no detailed description is given. GROSS APPEARANCE
Various authors have described malakoplakia of the bladder as raised nodules, involving the trigone and adjacent areas at the base of the bladder, varying in size from 0.5 cm to several centimeters in diameter. Some of the masses are rounded and almost pedunculated, others have broad bases and resemble plaques. None of these growths in the bladder had the appearance of papillomata, there being no fronds or villi. None showed ulceration but many of the larger ones are often umbilicated. MICROSCOPIC APPEARANCE
JVI alakoplakia. The appearance may strongly suggest tuberculosis, being distinguished by lack of caseation, exudation and calcification. Histologic examination of the nodules reveals collections of large, palely staining epithelioid cells arranged in the form of miliary tubercles, sometimes as isolated structures in comparatively normal tissue, and sometimes occurring in groups or strands. Giant cells are numerous, surrounded by outpouring of epithelioid cells and connective tissue stroma containing spindle cells (figs. 5, 6). Over 15 years ago I described the calcium-like inclusion bodies in the giant cells of malakoplakia tissue (5); this has been considered pathognomonic of this tissue. Sarcoids. Here the histologic picture also strongly suggests tuberculosis with lack of caseation, exudation or calcification. Giant cells are present as well as large epithelioid cells surrounded by connective tissue. Tumors of both types have a tendency to umbilicate but in neither type do they break down and ulcerate. Giant cells of sarcoids are often extremely large and irregular, showing many pale nuclei and containing peculiar inclusions of various sizes and shapes staining deeply in hematoxylin. These cell inclusions, repeatedly observed, give the appearance of calcified material. These inclusions have been repeatedly
MALAKOPLAKIA OF URINARY BLADDER AND SARCOIDOSIS
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reported as pathognomonic of malakoplakia. In both malakoplakia and sarcoid the reaction to tuberculin is very low. The globulin fraction of plasma proteins is markedly increased in both malakoplakia and sarcoidosis, depending directly on the amount of this foreign tissue present.
Frn. 5. Photomicrograph of skin sarcoid. giant cells with calcified inclusion bodies.
K ote epitheloid cells and extremely large
Frn. 6. Photomicrograph of biopsy specimen of malakoplakia, Case 2. and giant cells with inclusion bodies.
K oted epitheloid
CASE REPORTS
Case 1. No. 582, male, J. S., age 62, with hematuria but without symptoms of cystitis, was examined in June 1927, and found to have chronic pulmonary tuberculosis in the primary stage in the upper right lobe, chronic arthritis and hypertrophied prostate. There were albumin and casts in the urine but bacteria
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FRANCIS H. REDEWILL
were not demonstrable after continued search. There was no frequency, tenesmus or residual urine and pyelograms taken on each side showed the pelves to be negative as to pathologic signs. Four lavages of the kidney pelves with weak silver nitrate solution cleared up the hematuria. There were numerous raised, rounded, brownish soft plaques, varying in size from that of a pea to one coalesced nodule in the upper right portion of the bladder wall with about a 3 cm. spread. The plaques did not show ulceration. Upon removal of a small plaque with cystoscopic ronguer frozen sections showed typical malakoplakia cells with large epithelial cells. A diagnosis of malakoplakia of the urinary bladder was made. The patient was treated for four months. Some of the nodules disappeared and the remainder decreased in size. Case 2. No. 2256, a woman, M. L., aged 40, fell 1 week before from a street car. She came in on November 1941 complaining of pain in the right back, radiating around to the front and blood in the urine. Physical examination revealed brownish soft plaques distributed over the body, especially on the elbows, arms, chest and back and also two large ones on the sides of her cheeks. This condition which developed gradually over 1 year was symptomless. Diagnosis, generalized sarcoidosis and partial rupture of the right kidney as result of fall. Cystoscopy revealed sanguinous urine being expelled from the right ureter. There were no signs of internal hemorrhage, the patient was in fairly good shape. Treated expectantly, the condition cleared up. On examining the bladder I found brownish soft plaques above the interureteric ridge which I diagnosed as malakoplakia. I was struck by the similarity of the plaques on the surface of the body with the malakoplakia of the bladder. I induced the patient to allow me to make a biopsy of several sarcoids and also of the malakoplakia. Stained sections of both types revealed strikingly similar pathological changes. Below the mucous membrane, on the one hand and cutis on the other, I found a dissemination of giant cells with outpouring of large epithelioid cells surrounded by connective tissue stroma, spindle shaped cells, and calcified-like inclusions in the giant cells. ·wny cannot this so-called malakoplakia be a form of sarcoid? Many articles have been written on both of these conditions. However, no one has associated the one with the other. Let me summarize how closely related these two conditions are. SUMMARY
If it were possible to transplant malakoplakia of the bladder to the skin, lymph nodes or any other part of the body, it would be diagnosed sarcoid. Why? Because the gross and microscopic pathology of the former are similar to the latter, including (a) the large epithelioid cells, (b) giant cells with (c) corpus amylaciallike calcium inclusions that are characteristic of both types, (d) unless the growths impinge mechanically in some organ they are symptomless. (e) These symptomless types of both diseases as a rule heal spontaneously; (f) the globulin fraction of the plasma is increased in both types in direct proportion to the size
MALAKOPLAKIA OF URIKARY BLADDER AND SARCOIDOSIS
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and number of tumor masses. (g) The tumors of both types umbilicate, do not ulcerate; tubercle bacteria cannot be cultured from either. (h) There is often a tuberculous diathesis in the patient who harbors either type, though his tuberculin reaction is low. I believe that, if the scores of generalized sarcoidosis cases that have been reported had been cystoscoped, a great many would have been discovered to have so-called malakoplakia of the bladder, that is, bladder sarcoids. I have reported 1 case of generalized sarcoidosis that I found to have malakoplakia of the bladder, the pathology of biopsy specimens of both conditions being strikingly similar. Flood Bldg., San Francisco, Calif.