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Malacoplakia: Report of a Case with Observations on Experimental Production of the Lesion
Vol. 105, May
THE JOURNAL OF UROLOGY
Copyright © 1971 by The Williams & Wilkins Co.
Printed in U.S.A.
MALACOPLAKIA: REPORT OF A CASE WITH OBSERVATIONS ON EXPERIMENTAL PRODUCTION OF THE LESION N. RAGHUNATHA RAO From the Department o.f Pathology, Kasturba Medical College, Manipal, S. K., Mysore State, India
Malacoplakia, most commonly found in the urinary tract, has been described in other locations. While much has to be learned regarding the etiology and pathogenesis, the disease is considered to be the result of infection. The most distinctive features of the lesion are proliferated mononuclear histiocytes and the presence of Michaelis-Gutmann bodies that give staining reactions for calcium and iron. Herein is reported a case in which the lesion occurred in the kidney and observations on the experimental production of the disease in animals.
diagnosed and a nephrectomy was performed. The patient was given streptomycin and when last seen, 6 months postoperatively, she showed overall improvement. The kidney specimen weighed 450 gm. and measured 15 by 9 by 7 cm. The pelvis contained 300 ml. pus which was aspirated during the operation. The capsule was thickened and showed adhesions to the surface. Section showed destruction of the calices (fig. 2). The kidney substance was almost totally replaced by a firm white tissue. The pelvic aspect was shaggy, friable and reddish brown. Microscopic examination revealed that the renal tissue was almost completely replaced by sheets and streams of mononuclear histiocytes which had abundant reticulated or vacuolated cytoplasm with eosinophilic granules (fig. 3). There was an admixture of polymorphocytes, lymphocytes and plasma cells. In the few surviving areas of cortex the glomeruli showed hyalinization. Areas of fibrosis were found at the periphery of the lesion close to the surviving areas of the cortex. Mononuclear histiocytes were identifiable amid the collagen bundles in these areas. Within and outside the mononuclear cells Michaelis-Gutmann bodies were seen especially well in periodic acid, Schiff (PAS) and von Kossa preparations. Imprints stained with 0.5 per cent aqueous toluidine blue and Gram's stain showed capsulated gramnegative rods in singles and clusters within the histiocytic cytoplasm (fig. 4). These were seen even in areas which did not appear necrotic, where only well preserved histiocytes were seen. An occasional blood vessel showed thrombus. Material from the kidney was cultured in several commonly used media. The organism that was grown was gram-negative and nonmotile, it did not ferment lactose on 2 days of incubation but did ferment glucose, sucrose and mannitol with acid and gas. Indole was produced, a methyl red test was positive and the VogesProskauer reaction was negative. The organism did not split urea.
CASE REPORT
A 40-year-old woman was admitted to the hospital with complaints of loin pain several weeks in duration, fever with rigors and burning during micturition. She had a right renal mass. The hemoglobin was 5 gm. per 100 ml. and a hypochromic microcytic anemia was noted. The total leukocyte count was 7,200 cells per cu. mm. with a normal differential count. The b~ood sedimentation rate was 140 mm. per hour. The blood urea nitrogen was 15 mg. per 100 ml. An excretory urogram showed the right kidney to be non-functioning. On cystoscopy pus was seen trickling out of the right ureteral orifice. The bladder mucosa showed no lesion. Clinical diagnosis was tuberculous pyonephrosis. Particles seen in cystoscopic washings were embedded in paraffin. Sections of these particles were stained with hematoxylin and eosin, revealing a few rounded bodies that were hematoxylinophilic amid dense collections of polymorphocytes and mononuclear cells (fig. 1). These bodies reacted to von Kossa's stain for calcium and the Perls' stain for iron and were, therefore, identified as Michaelis-Gutmann bodies. Renal malacoplakia was Accepted for publication September 1, 1970. Current address: Department of Pathology, Medical Center, The Voluntary Heal th Services, Madras 20, India. Requests for reprints: Dr. Belur Bhagavan, Department of Pathology, Sinai Hospital, Baltimore, Maryland 21215. 611
612
RAO EXPERIMENTAL LESIONS
A 24-hour broth culture was injected intraperitoneally into 2 rats. Both rats died 24 hours later and culture of heart blood yielded the organism. No lesions were seen. A 24-hour broth culture was injected subcutaneously into a rabbit. A swelling at the site of injection gradually grew in size. The swelling, 2 cm. in diameter, which was excised after 6 weeks, showed poor delimitation from the surrounding tissues and contained pultaceous material in its core. Microscopic examination of the central pultaceous material showed pus cells and sheets of histiocytes with vacuolated and granular cytoplasm. No Michaelis-Gutmann bodies were observed even after microincineration. Culture of the material yielded an organism of the type that was originally injected. Subcultures of this organism injected subcutaneously into 2 rabbits failed to produce the lesion. Material from the nephrectomy specimen was aseptically transferred into the peritoneal cavity of 2 rats. A swelling developed in both rats at the site of implantation. These were 2 cm. in diameter after 3 months when the rats were killed and the tissue was removed. The swellings showed adhesions to the surrounding tissues and contained a central core of pultaceous material. Material from the pultaceous core was reimplanted into 2 more rats. A similar lesion developed in 1 rat at the end of 2 months. However reimplantation of this material into 2 other rats failed to produce the lesion.
Fm. 2. Cut section of kidney shows destruction of calices and almost total replacement of renal substance by firm white tissue of malacoplakia.
Fm. 3. Sheet of malacoplakia histiocytes with hematoxylinophilic inclusions. H & E, reduced from X400.
Fm. 1. Hematoxylinophilic, roundedMichaelisGutmann bodies in cystoscopic washings show "pseudobudding" (arrow). H & E, reduced from X400.
Microscopically the core material showed areas with only pus cells, which also showed several foci of calcification. Elsewhere the tissue showed collections of mononuclear cells with a variable admixture of polymorphocytes, lymphocytes and plasma cells (fig. 5, A). Michaelis-Gutmann bodies were identified by von Kossa's and Perls' stains. At the margins the pultaceous core showed fibrosis. It was observed that in these areas the histiocytes assumed a spindle shape and transitions between these and cells appearing like fibroblasts were observed (fig. 5, B).
MALACOPLAKIA
613
Fm. 4. Histiocyte in imprint with bacterial rods in cytoplasm (arrow). Toluidine blue, reduced from Xl,000. DISCUSSION
Malacoplakia involves the bladder most frequently. 1 • 2 In many cases involvement of kidney and ureter has been recorded. Involvement of kidney alone was recorded by Purpon and Perez Tamayo 3 and and in one of Smith's 24 cases. At the time of Si.izer's report only 5 cases were believed to have been reported in the literature with involvement confined to the kidney. The number of recorded cases of malacoplakia is small but it appears that the disease is more common than the literature would indicate. Yunis and associates found 3 cases in a community hospital with 325 beds. 5 Within I year the lesion was encountered twice in a hospital with 200 beds. These 2 cases involved the one reported herein and a case in which the appendix, omentum and mesenteric and retroperitoneal lymph nodes were involved. We earlier reported a case found in a hospital only 40 miles 1 Melicow, M. M.: Malacoplakia: report of case, review of literature. J. Ural., 78: 33, 1957. 2 Smith, B. H.: Malacoplakis, of the urinary tract: a study of twenty-four cases. Amer. J. Clin. Path., 43: 409, 1965. 3 Purpon, I. and Perez Tamayo, R.: Malacoplakia of the kidney. J. Ural., 84: 231, 1960. 4 Seizer, I. T.: A rare localization of malakoplakia: renal pelvis. J. Urol., 95: 746, 1966. 5 Yunis, E. J., Estevez, J. M., Pinzon, G. J. and Moran, T. J.: Malacoplakia. Discussion of pathogenesis and report of three cases including one of fatal gastric and colonic involvement. Arch. Path., 83: 180, 1967. 6 Rao, N. R.: Malacoplakia of broad ligam.ent,
Fm. 5. A, section of lesion in rat shows histiocytes as in malacoplakia. H & E, reduced from X60. B, area of commencing fibrosis in rat lesion H & E, reduced from X240. The cases reported Purpon and Perez Tamayo and by Si.izer did not show ::\Iichaelisinguinal region, and endometrium. Arch. Path., 88: 85, 1969.
614
RAO
Gutmann bodies, but Si:izer did find PAS-positive, von Rossa-positive granules. It is not clear whether in the absence of these bodies one could be certain of a diagnosis of malacoplakia, especially in the kidneys, since, as has been pointed out by Rios-Dalenz and Peacock, it would be difficult to exclude a diagnosis of xanthogranulomatous pyelonephritis. 7 Diagnosis of the lesion in the patient herein described was made possible by identification of MichaelisGutmann bodies in particles in the cystoscopic washings. Cytological diagnosis of malacoplakia in the urine sediment has been discussed by Melamed. 8 Several previous reports have discussed the histological and histochemical features of the lesion and the Michaelis-Gutmann bodies. Gram-negative bacilli were found in the necrotic areas in 5 of 9 patients examined by Brown and Smith. 9 Yunis and associates also found bacteria in one of their 3 cases. In each of the 3 cases studied by us bacterial rods were demonstrable in the tissues. Examination of imprints from unfixed tissue for bacteria would be of great value in determining if all cases of malacoplakia would show these, particularly since the observations on histological preparations have so often been negative. The lesions seen in the experimental rats with the Michaelis-Gutmann bodies and mononuclear histiocytes bore great similarity to malacoplakia. However, Heptinstall, who confirmed the diagnosis in this case and agreed that the lesions in the rat had many of the same features, wondered if one would be justified in calling the animal lesions malacoplakia. He pointed out that similar lesions are seen often in experimental pyelonephritis in rats. He considered these to be a peculiar reaction to infection. The absence of Michaelis-Gutmann bodies in the rabbit lesion is interesting. Yunis and associates su12:gested 7 Rios-Dalenz, J. L. and Peacock, R. C.: Xanthogranulomatous pyelonephritis. Cancer, 19: 289, 1966. 8 Melamed, M. R.: The urinary sediment cytology in a case of malakoplakia. Acta Cytol., 6: 471, 1962. 9 Brown, R. C. and Smith, B. H.: Malacoplakia of the testis. Amer. J. Clin. Path., 47: 135, 1967.
that these bodies represent deposition of calcium and iron in the granules of mast cells as in calciphylaxis, the mast cell proliferation being secondary to a chronic infection. In the rabbit the question of presence, distribution and density of population of the mast cells remains controversial.10 The inability of subcultures to produce the lesion and failure to reproduce the disease by repeated implantations may probably be related to the number of organisms introduced and their virulence. Terner and Lattes suggested that the Michaelis-Gutmann bodies contain a non-human glycolipid, probably of bacterial origin.11 They also suggested that the quantity of bacterial glycolipid released at one time may govern the occurrence of malacoplakia and postulated that when massive destruction of an appropriate micro-organism and a local release of glycolipid occurred the stage was set for malacoplakia. While the present experiments leave a number of questions unanswered, they at least lend support to the belief that the lesions of malacoplakia result from a chronic infection. It is also probable that more than one organism is capable of causing the lesion. In our other case which involved the appendix a different organism, of the genus Klebsiella, was isolated. SUMMARY
A case of malacoplakia involving the kidney only is described. Diagnosis of the lesion was made possible by the discovery of MichaelisGutmann bodies in particles floating in cystoscopic washings. Implantation of the material from the kidney into the peritoneal cavity of rats gave rise to lesions that bore similarity to malacoplakia. Dr. Robert H. Heptinstall confirmed the diagnosis. Dr. A. S. Narayan assisted in the study of this case and Mr. U. J. Devadiga helped with the preparation of photomicrographs. 10 Selye, H.: The Mast Cells. London: Butterworth & Co., Ltd., pp. 130-131, 1965. . 11 Terner, J. Y. and Lattes, R.: Malakoplakia of colon and retroperitoneum. Report of a case with a histochemical study of the Michaelis-Gutmann inclusion bodies. Amer. J. Clin. Path., 44: 20, 1965.
THE JOURNAL OF UROLOGY
Copyright © 1971 by The Williams & Wilkins Co.
Printed in U.S.A.
MALACOPLAKIA: REPORT OF A CASE WITH OBSERVATIONS ON EXPERIMENTAL PRODUCTION OF THE LESION N. RAGHUNATHA RAO From the Department o.f Pathology, Kasturba Medical College, Manipal, S. K., Mysore State, India
Malacoplakia, most commonly found in the urinary tract, has been described in other locations. While much has to be learned regarding the etiology and pathogenesis, the disease is considered to be the result of infection. The most distinctive features of the lesion are proliferated mononuclear histiocytes and the presence of Michaelis-Gutmann bodies that give staining reactions for calcium and iron. Herein is reported a case in which the lesion occurred in the kidney and observations on the experimental production of the disease in animals.
diagnosed and a nephrectomy was performed. The patient was given streptomycin and when last seen, 6 months postoperatively, she showed overall improvement. The kidney specimen weighed 450 gm. and measured 15 by 9 by 7 cm. The pelvis contained 300 ml. pus which was aspirated during the operation. The capsule was thickened and showed adhesions to the surface. Section showed destruction of the calices (fig. 2). The kidney substance was almost totally replaced by a firm white tissue. The pelvic aspect was shaggy, friable and reddish brown. Microscopic examination revealed that the renal tissue was almost completely replaced by sheets and streams of mononuclear histiocytes which had abundant reticulated or vacuolated cytoplasm with eosinophilic granules (fig. 3). There was an admixture of polymorphocytes, lymphocytes and plasma cells. In the few surviving areas of cortex the glomeruli showed hyalinization. Areas of fibrosis were found at the periphery of the lesion close to the surviving areas of the cortex. Mononuclear histiocytes were identifiable amid the collagen bundles in these areas. Within and outside the mononuclear cells Michaelis-Gutmann bodies were seen especially well in periodic acid, Schiff (PAS) and von Kossa preparations. Imprints stained with 0.5 per cent aqueous toluidine blue and Gram's stain showed capsulated gramnegative rods in singles and clusters within the histiocytic cytoplasm (fig. 4). These were seen even in areas which did not appear necrotic, where only well preserved histiocytes were seen. An occasional blood vessel showed thrombus. Material from the kidney was cultured in several commonly used media. The organism that was grown was gram-negative and nonmotile, it did not ferment lactose on 2 days of incubation but did ferment glucose, sucrose and mannitol with acid and gas. Indole was produced, a methyl red test was positive and the VogesProskauer reaction was negative. The organism did not split urea.
CASE REPORT
A 40-year-old woman was admitted to the hospital with complaints of loin pain several weeks in duration, fever with rigors and burning during micturition. She had a right renal mass. The hemoglobin was 5 gm. per 100 ml. and a hypochromic microcytic anemia was noted. The total leukocyte count was 7,200 cells per cu. mm. with a normal differential count. The b~ood sedimentation rate was 140 mm. per hour. The blood urea nitrogen was 15 mg. per 100 ml. An excretory urogram showed the right kidney to be non-functioning. On cystoscopy pus was seen trickling out of the right ureteral orifice. The bladder mucosa showed no lesion. Clinical diagnosis was tuberculous pyonephrosis. Particles seen in cystoscopic washings were embedded in paraffin. Sections of these particles were stained with hematoxylin and eosin, revealing a few rounded bodies that were hematoxylinophilic amid dense collections of polymorphocytes and mononuclear cells (fig. 1). These bodies reacted to von Kossa's stain for calcium and the Perls' stain for iron and were, therefore, identified as Michaelis-Gutmann bodies. Renal malacoplakia was Accepted for publication September 1, 1970. Current address: Department of Pathology, Medical Center, The Voluntary Heal th Services, Madras 20, India. Requests for reprints: Dr. Belur Bhagavan, Department of Pathology, Sinai Hospital, Baltimore, Maryland 21215. 611
612
RAO EXPERIMENTAL LESIONS
A 24-hour broth culture was injected intraperitoneally into 2 rats. Both rats died 24 hours later and culture of heart blood yielded the organism. No lesions were seen. A 24-hour broth culture was injected subcutaneously into a rabbit. A swelling at the site of injection gradually grew in size. The swelling, 2 cm. in diameter, which was excised after 6 weeks, showed poor delimitation from the surrounding tissues and contained pultaceous material in its core. Microscopic examination of the central pultaceous material showed pus cells and sheets of histiocytes with vacuolated and granular cytoplasm. No Michaelis-Gutmann bodies were observed even after microincineration. Culture of the material yielded an organism of the type that was originally injected. Subcultures of this organism injected subcutaneously into 2 rabbits failed to produce the lesion. Material from the nephrectomy specimen was aseptically transferred into the peritoneal cavity of 2 rats. A swelling developed in both rats at the site of implantation. These were 2 cm. in diameter after 3 months when the rats were killed and the tissue was removed. The swellings showed adhesions to the surrounding tissues and contained a central core of pultaceous material. Material from the pultaceous core was reimplanted into 2 more rats. A similar lesion developed in 1 rat at the end of 2 months. However reimplantation of this material into 2 other rats failed to produce the lesion.
Fm. 2. Cut section of kidney shows destruction of calices and almost total replacement of renal substance by firm white tissue of malacoplakia.
Fm. 3. Sheet of malacoplakia histiocytes with hematoxylinophilic inclusions. H & E, reduced from X400.
Fm. 1. Hematoxylinophilic, roundedMichaelisGutmann bodies in cystoscopic washings show "pseudobudding" (arrow). H & E, reduced from X400.
Microscopically the core material showed areas with only pus cells, which also showed several foci of calcification. Elsewhere the tissue showed collections of mononuclear cells with a variable admixture of polymorphocytes, lymphocytes and plasma cells (fig. 5, A). Michaelis-Gutmann bodies were identified by von Kossa's and Perls' stains. At the margins the pultaceous core showed fibrosis. It was observed that in these areas the histiocytes assumed a spindle shape and transitions between these and cells appearing like fibroblasts were observed (fig. 5, B).
MALACOPLAKIA
613
Fm. 4. Histiocyte in imprint with bacterial rods in cytoplasm (arrow). Toluidine blue, reduced from Xl,000. DISCUSSION
Malacoplakia involves the bladder most frequently. 1 • 2 In many cases involvement of kidney and ureter has been recorded. Involvement of kidney alone was recorded by Purpon and Perez Tamayo 3 and and in one of Smith's 24 cases. At the time of Si.izer's report only 5 cases were believed to have been reported in the literature with involvement confined to the kidney. The number of recorded cases of malacoplakia is small but it appears that the disease is more common than the literature would indicate. Yunis and associates found 3 cases in a community hospital with 325 beds. 5 Within I year the lesion was encountered twice in a hospital with 200 beds. These 2 cases involved the one reported herein and a case in which the appendix, omentum and mesenteric and retroperitoneal lymph nodes were involved. We earlier reported a case found in a hospital only 40 miles 1 Melicow, M. M.: Malacoplakia: report of case, review of literature. J. Ural., 78: 33, 1957. 2 Smith, B. H.: Malacoplakis, of the urinary tract: a study of twenty-four cases. Amer. J. Clin. Path., 43: 409, 1965. 3 Purpon, I. and Perez Tamayo, R.: Malacoplakia of the kidney. J. Ural., 84: 231, 1960. 4 Seizer, I. T.: A rare localization of malakoplakia: renal pelvis. J. Urol., 95: 746, 1966. 5 Yunis, E. J., Estevez, J. M., Pinzon, G. J. and Moran, T. J.: Malacoplakia. Discussion of pathogenesis and report of three cases including one of fatal gastric and colonic involvement. Arch. Path., 83: 180, 1967. 6 Rao, N. R.: Malacoplakia of broad ligam.ent,
Fm. 5. A, section of lesion in rat shows histiocytes as in malacoplakia. H & E, reduced from X60. B, area of commencing fibrosis in rat lesion H & E, reduced from X240. The cases reported Purpon and Perez Tamayo and by Si.izer did not show ::\Iichaelisinguinal region, and endometrium. Arch. Path., 88: 85, 1969.
614
RAO
Gutmann bodies, but Si:izer did find PAS-positive, von Rossa-positive granules. It is not clear whether in the absence of these bodies one could be certain of a diagnosis of malacoplakia, especially in the kidneys, since, as has been pointed out by Rios-Dalenz and Peacock, it would be difficult to exclude a diagnosis of xanthogranulomatous pyelonephritis. 7 Diagnosis of the lesion in the patient herein described was made possible by identification of MichaelisGutmann bodies in particles in the cystoscopic washings. Cytological diagnosis of malacoplakia in the urine sediment has been discussed by Melamed. 8 Several previous reports have discussed the histological and histochemical features of the lesion and the Michaelis-Gutmann bodies. Gram-negative bacilli were found in the necrotic areas in 5 of 9 patients examined by Brown and Smith. 9 Yunis and associates also found bacteria in one of their 3 cases. In each of the 3 cases studied by us bacterial rods were demonstrable in the tissues. Examination of imprints from unfixed tissue for bacteria would be of great value in determining if all cases of malacoplakia would show these, particularly since the observations on histological preparations have so often been negative. The lesions seen in the experimental rats with the Michaelis-Gutmann bodies and mononuclear histiocytes bore great similarity to malacoplakia. However, Heptinstall, who confirmed the diagnosis in this case and agreed that the lesions in the rat had many of the same features, wondered if one would be justified in calling the animal lesions malacoplakia. He pointed out that similar lesions are seen often in experimental pyelonephritis in rats. He considered these to be a peculiar reaction to infection. The absence of Michaelis-Gutmann bodies in the rabbit lesion is interesting. Yunis and associates su12:gested 7 Rios-Dalenz, J. L. and Peacock, R. C.: Xanthogranulomatous pyelonephritis. Cancer, 19: 289, 1966. 8 Melamed, M. R.: The urinary sediment cytology in a case of malakoplakia. Acta Cytol., 6: 471, 1962. 9 Brown, R. C. and Smith, B. H.: Malacoplakia of the testis. Amer. J. Clin. Path., 47: 135, 1967.
that these bodies represent deposition of calcium and iron in the granules of mast cells as in calciphylaxis, the mast cell proliferation being secondary to a chronic infection. In the rabbit the question of presence, distribution and density of population of the mast cells remains controversial.10 The inability of subcultures to produce the lesion and failure to reproduce the disease by repeated implantations may probably be related to the number of organisms introduced and their virulence. Terner and Lattes suggested that the Michaelis-Gutmann bodies contain a non-human glycolipid, probably of bacterial origin.11 They also suggested that the quantity of bacterial glycolipid released at one time may govern the occurrence of malacoplakia and postulated that when massive destruction of an appropriate micro-organism and a local release of glycolipid occurred the stage was set for malacoplakia. While the present experiments leave a number of questions unanswered, they at least lend support to the belief that the lesions of malacoplakia result from a chronic infection. It is also probable that more than one organism is capable of causing the lesion. In our other case which involved the appendix a different organism, of the genus Klebsiella, was isolated. SUMMARY
A case of malacoplakia involving the kidney only is described. Diagnosis of the lesion was made possible by the discovery of MichaelisGutmann bodies in particles floating in cystoscopic washings. Implantation of the material from the kidney into the peritoneal cavity of rats gave rise to lesions that bore similarity to malacoplakia. Dr. Robert H. Heptinstall confirmed the diagnosis. Dr. A. S. Narayan assisted in the study of this case and Mr. U. J. Devadiga helped with the preparation of photomicrographs. 10 Selye, H.: The Mast Cells. London: Butterworth & Co., Ltd., pp. 130-131, 1965. . 11 Terner, J. Y. and Lattes, R.: Malakoplakia of colon and retroperitoneum. Report of a case with a histochemical study of the Michaelis-Gutmann inclusion bodies. Amer. J. Clin. Path., 44: 20, 1965.