Malacoplakia of the Urinary Tract

Vol. 100, Nov. Printed in U.S.A.

THE JOURNAL OF UROLOGY

Copyright © 1968 by The Williams & Wilkins Co.

~vIALACOPLAKIA OF THE URINARY TRACT CLARENCE SCHNEIDERMAN

AND

MORRIS A. SIMON

From the Departments of Urology and Pathology, The Jewish General Hospital, i"\fontreal, Canada

Although the basic lesion of malacoplakia in the urinary tract is generally regarded as benign in character, its occurrence in certain areas may lead to obstructive changes with serious consequences. A recent case involving primary lesions of the renal pelvis on one side, both ureters and, ultimately, the bladder illustrates the possible severity of this relatively uncommon pathological entity. In a review of the literature in 1957 Melicow found 67 cases of malacoplakia to which he added 1 case of his own. 1 The majority of these cases were found at autopsy. Subsequently sporadic cases have been reported of malacoplakia involving the pelvis, ureters, kidney, bladder, prostate and testis. 2-17 Goldman's report

in 1965 of malacoplakia involving the prostate gland brought the total number of reported cases to 92.1 5 To these cases may be added those of Hoffmann and Garrido involving the prostate,1 4 Siizer involving the renal pelvis16 and Brown and Smith involving the testis.17 The fatal case of Scott and Scott presented extensive involvement of the urinary tract with extension to the retroperitoneal structures and showed typical histological characteristics of malacoplakia within the adjacent perinephric abscesses. 4

Accepted for publication November 21, 1967. 1 JYielicow, M. M.: Malacoplakia: report of case, review of literature. J. Urol., 78: 33-40, 1957. 2 Haukohl, R. S. and Chinchinian, H.: l\1alakoplakia of the testicle. Report of a case. Amer. J. Clin. Path., 29: 473-478, 1958. 3 Hand, J. R.. and Sullivan, A. W.: Malakoplakia of the urinary tract; report of a case. Portland Clin. Bull., 12: 1-10, 1958. 4 Scott, E. V. Z. and Scott, W. F., Jr.: A fatal case of malakoplakia of the urinary tract. J. U rol., 79: 52-56, 1958. 5 Waard, T., de: Malacoplakie. Ned. Tschr. Geneesk., 102: 1530-1531, 1958. 6 Carruthers, N. C.: Malakoplakia, report of a case. Canad. J. Surg., 2: 213-214, 1959. 7 Haschek, H.: Malacoplakia and chronic urinary infection. Wien Med. Wschr., 109: 647-648, 1959.

8 Purpon, I. and Tamayo, R. P.: Malacoplakia of the kidney. J. Urol., 84: 231-235, 1960. 9 Curtis, W.R., Bozzell, J. D. and Green, C. L.: Malacoplakia of bladder; report of a case successfully treated with anti-tuberculosis medical therapy. J. Urol., 86: 78-81, 1961. 10 Jozsa, L.: Contributions to the pathogenesis of malakoplakia. Z. Urol., 54: 465-470, 1961. 11 Angelov, A.: Malacoplakia of the urinary tract. Z. Urol., 55: 371-376, 1962. 12 McKiel, C. F., Jr., Eisenstein, R. and McDonald, J. H.: Morphological and microbiological studies in malacoplakia. J. Urol., 88: 236-242, 1962. 13 Weber, H. F.: Malakoplakia of the urinary bladder. Urol. Inter., 13: 350-361, 1962. 14 Hoffmann, E. and Garrido, M.: Malakoplakia of the prostate: report of a case. J. Urol., 92:

311-313, 1964.

15 Goldman, R. L.: A case of malacoplakia with involvement of the prostate gland. J. Urol.,

CASE REPORT

A 53-year-old white woman was admitted to the Jewish General Hospital on December 6, 1966 with a history of left loin pain, chills and fever. The woman had been treated by her family physician for 3 months because of recurrent urinary tract infection. She had received a variety of antibiotics to combat a heavy Escherichia coli infection in the urine, with no apparent improvement in her symptoms. "\Vhen seen in consultation on December 2, the woman appeared acutely ill with a temperature of 101.6 and a tender mass in the left loin. Urinalysis on admission to the hospital showed albumin plus, loaded with white blood cells per high power field (many clumps). The white blood count was 14,500 per cu. mm. and the hemoglobin was 74 per cent (11.6 gm.). The sedimentation rate was 55 mm. per hour. A differential smear showed 83 polymorphonuclear leukocytes, 10 lymphocytes and 7 eosinophils. Before and after meal sugar were 100 and 116 mg. per cent, respectively. Blood urea nitrogen was 22 mg. per cent. Creatinine was 1.5 and uric acid was 7 .2 mg. per cent. The culture of urine made when the patient was admitted to the hospital was negative. Subsequent cultures done on December 9 and 21 showed 10,000 and more than 100,000 E. coli per ml., respectively. The E. coli was sensitive to ampicillin, kanamycin, furadantin, polymyxin B, colistin and chloramphenicol and was resistant to 17 Brown, R. C. and Smith, B. H.: Malacoplakia of the testis. Amer. J. Clin. Path., 47: 135-147,

93: 407-410, 1965.

Siizer, I. T.: A rare localization of malakoplakia: renal pelvis. J. Urol., 95: 746-748, 1966. 16

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MALACOPLAKIA OF URINARY TRACT

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FIG. 1. A, preoperative excretory urogram shows marked dilatation of lefi renal pelvis and ca1yce.-;, with sharp cutoff at left ureteropelvic junction. B, retrograde ureterogram shows complete obsin1.c·tiou to contrast medium below ureteropelvic jnnction, No urinary drainage wns obtai11ed 1hrongh meteral catheter

tetracycliDe, sulfonamides and ueggram. Acidfast smears, cultures of the mine and chest x-ray were negative. T,Yo excretory urograms taken immediately prior to hospitalization aud OD admission to the hospital showed delayed excretion of contrast rnedium from the left kidney, with hyclronephro-sis and a cutoff at the ureteropelvic junction (fig. 1, A.). In the 2-hour film there appeared to be a gap in the upper third of the left ureter ,Yith dilatation of the ureter below this level. The right renal pelvis and calyces appeared normal; however, the lower portion of ureter \\'as dilated and somewhat tortuous. On cystoscopy the bladder shmwd a mild redness and edema of the mucosa. Obstruction 11·hich was encountered on passage of F.5 catheter into the upper left ureter could not be m·ercomc. An attempted ureterogram ,'3howcd complete obstruction at the distal encl of' the meteral catheter (19 cm. level) which appeared to be ,several centimeters below the antegrade cutoff at the ureteropelvic junction, as sPen on the retrograde pyelogram (fig. l, B). The differential diag1Josis at this point inYolved an infected left hydronephrosis caused either by a turnor of the ureter, possibly polypoid in nature, or by extrinsic pressure on the UJJJ)er ureter with

Fm. 2. Gross specimen of bisected left shows multiple raised nodules of ma]acoplakia and below nreteropelvic junction, rer;ulting in obstruction. Lower portion of renal pelviR shows extensive hemorrhagic nnd n!C'erntive infimn-mntory changes.

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Fm. 3. ~'i, low power view of nodule in upper ureter shows elevated lesion of malacoplakia lying between epithelium and muscle layer. B, high power view reveals details of large, pale, macrophagic cells. In center of photomicrograph circular target-like structure is seen within cytoplasm of cell. This was only structure resembling so-called calcospherite.

secondary hydronephrosis. It was difficult to adequately explain the two points of obstruction in the upper left ureter at the ureteropelvic junction and several centimeters below, which were so readily visualized on antegrade and retrograde pyelography. On December 9 exploration of the left loin revealed that the kidney was under marked tension, with corrniderable surrounding edema and perinephritic adhesions. A solid nodular mass was palpated in the upper third of the ureter, and on opening the latter over the mass, a gush of thick purulent urine from the renal pelvis ensued. The ureteropelvic junction was incised and 2 similar nodules presented which appeared discrete. The initial impression was that of multiple solid tumors arising from the ureteral wall and invaginating the mucosa. The pelvis had a similar ridge of thickened confluent nodules with marked ulceration and redness. N ephrectomy was then performed including the upper half of thP ureter. The main findings on inspection of the kidney were a semilunar valvelike mass at the ureteropelvic junction measuring 0.6 by 0.3 cm. and two smooth nodular lesions, one beneath the site of obstruction, measuring 0.5 by 0.2 cm. (fig. 2). Essentially, the microscopic appear.1nce taken through the nodule at the ureteropelvic junction showed an ulcerated, granulornatous lesion com-

posed primarily of large numbers of pale histiocytes or macrophages with abundant cytoplasm and uniform, vesicular nuclei (fig. 3). A careful search failed to reveal any intracytoplasmic inclusions of any sort which could be considered as so-called Michaelis-Gutmann bodies. The nodules below the ureteropelvic junction were essentially similar in microscopic appearance, and no calcospherites were seen with the exception of a single cell in which an indistinct target-like structure was seen in the cytoplasm. Because of the failure to find any MichaelisGutmann bodies and because, clinically, no lesions were noted in the bladder where malacoplakia usually first appears, a diagnosis of nodular pyelitis and ureteritis was made. The possibility of malacoplakia was considered in a discussion of the differential diagnosis. Postoperatively the patient was given ampicillin and then furadantin, because of a heavy growth of E.coli which was found on urine culture, 2 weeks after nephrectomy. Convalescence was uneventful, but a severe drug eruption developed while the patient was on furadantin and, accordingly, all drugs were discontinued. In February 1967 urinalysis revealed the presence of a large number of pus cells and repeated urine cultures showed a significant growth of E.coli. The patient was given tetra-

JVJALACOPLAKIA OF URINARY 'l'RACT

cyclinc, ampicillin and ,mlfonamides during the next 2 months, but continued to exhibit marked pyuria although she was completely asymptomatic. Cystoscopy on .June 8 reYealed nurnernus discrete pinkish-gray t1odules which appeared to bulge through the bladder rnucosa. These nodules appcarecl strikingly similar to those ~een in the left ureter and renal JJelvis, and at this point the conviction grew that this was trnly a case of malacoplakia. The patient was then seen in comultation by Dr Da\·icl C. l-tz, at the l\layo Clinic, a summary of whose fimlings follows. An exeretmy urngram shmwd a pernisteut defect in the terminal few centimeters of the right ureter. At cystoscopy there were multiple submucosal nodules which lweamc more confluent across the base of the bladder. Bilateral uretemgram., showed filling defect., in each meter, consistent with i1wolvement of each system. A biopsy of the bladder lesions and material rnbmitted from the 11ephrectomy ~pecimen ,vere studic,d by ~en">ral pathoogi,ts, who were i11 agreement with the diagnosis of malacoplakia. These pathologists also observed the unusual absence of inclnsicm of calcific bodies but the general histologic pattern, in their >tnalysis, could only be classified as malacoplakia. The characteristic E.coli appeared on several urine cultures. It was recommended that the patient be maintained on long-term antibiotic therapy. She was ginn 1 gm. ampicilliu, 4 times daily. After 1 week the aforementioned dosage was reduced to 250 mg, daily and 5 gm. gantrisin, 4 times daily was added. Repeated cultures of the urine during July and August 1967 showed no significallt bacteriuria and repeated urinalyses have been negative. The patient remains completely asymptomatic but it is proposed to continue long-term antibiotic therapy. Cystoscopy on September 13 showed complete disappearance of the previously noted rnalacoplakic nodules in the bladder. DISCUSSTOK

l\Ialacoplakia is essentially a granulomatous lesion involving the urinary tract. The disease occurs more commonly in female subjects (ratio of 4 to 1) and has its highest incidence in patients in their fifth decade. The condition was first described by lviichaelis and Gutmann in 190218 18 Michaelis, L. and Gutmann, C.: Ueber Eisehlusse in Blasentumoren. Ztschr. f. klin. Med., 47: 208-215, 1902.

and the term '·rnalakoplakia" was JJroposecl by von Han,,;emann in 1903 (Grerk clerin:1tiou. rnalakos, soft, plakos, plaque). 19 The lesions are 11rimarily seeu in the bladdcr but may involve the ureter, reual pch·is and, rarely, the rrnal parenchyrna, retropcrito11eai strnctures, prostate aud testis. The unusual case~ of Haukohl and C'hi11chi11ia11, 2 and Brown am! Srnith, 17 involving the testicle, suggest that thi, disease entity is uot confined solely to the urillt1l") tract. The lesions arc multiple, raiser!, discrete plaques or nodules varying from 0.1 mm. to 3 cm., with occasional confluence creating a much mass. The nodules appear as greyish-yellow 01· pinkish-brown excrescences ll"hich seem t,, i1wagiuatc the; mucosa and show circumferential hyperemia aucl oc:casionall>· e<:ntrnl ulceration In cases in which the disease prncess involves the ureter, ureteral orifice or bladder neck, s,:courlar~' obstn1ctive changes may occur ,Yith se\·ere darn-aging effects, such as i11 our case and the fatal case cited by Scott and Scott. 4 Y\Then confined ti., the bladder the character of the disease generally benign. Histologically the plaques arn composed principally of histiocytes (Hansemaun cell,) and of collections of lymphocytes. The large phagocytic mononuclear cells often contain the classical l\'Iichaelis-Gutmann bodies which are round, basophilic and laminated. They are thought to be cytoplasmic concleusations, often eontaini11g deposits of calcium and iron. Although the etiology of rnalacoplakia uncertain, it is generally agreed that the cliseas(, entity is a granuloma, often associated with chronic urinary tract infection principally clue to E.coli. Other suggested causes include neoplasm, tuberculosis, Boeck's sarcoid, fungal and viral disease. l\IcKiel and associates reported a case of malacoplakia and described the ultrastructure of the lesion as demonstrated by electron micro~copy, and bacterial, viral and fungal ;-;tucliC's.12 They concluded that the basic nature of malaeoplakia was a chronic inflammatory process located beneath thC' urothelium. They noted Urn t the predominant cellular components are the plasma cell and histiocyte, and considered the genesis of the calcareous spherules or l\Iichaeli~Gutmann bodies as being formed from cyto19 von Hansemam1, D.: Liber malakoplakie der harnblase. Yirch. Arch. f. path. Anat., 173: ::l02,

1903.

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plasmic granules which stain red with the periodic acid Schiff reagent. They attributed the formation of typical plaques as a response to a chronic inflammatory state, with histiocytic phagocytosis of fatty acids and/or polysaccharides and their subsequent calcification without the influence of either fungi or viruses. The clinical picture is that of chronic urinary tract infection, with frequency, dysuria, pyuria and hematuria being of most frequent occurrence. In cases in which the upper urinary tract is involved by obstruction, pain and recurrent pyrexia are observed. In many incidences the disease is asymptomatic. There are no characteri~tic radiographic findings, and the cystoscopic appearance is multiple raised nodular excrescences, whether circumscribed or confluent, pinkish-brown and, occasionally, ulceration. The differential diagnosis includes tumor, tuberculosis or other varieties of chronic inflammatory disease. Biopsy of the lesion may be difficult to interpret and may require considerable study. Therapy is directed at eradication of the chronic infection, usually due to E.coli, and must of necessity be long-term in order to achieve a permanent arrest or regression of the disease. If upper tract obstruction and infection occur (as in our case) removal of the diseased kidney and ureter may be necessary. Fulguration of localized bladder lesions and instillation of silver nitrate have been used in some instances. King 20

°King,

K. B. Urologists Letter Club, March 1957 (cited by Scott and Scott 4 ). 2

and Curtis and associates 9 reported an encouraging response to antituberculous therapy with streptomycin and para-aminosalicylic acid, although the rationale for such treatment appears vague. SUMMARY

A case is presented of malacoplakia of the urinary tract with extensive involvement of the renal pelvis, both ureters and bladder and obstruction and infection supervening. The condition necessitated a nephrectomy. Review of the disease process points to the pathological lesion as probably being the result of a chronic inflammatory granulomatous process located beneath the urothelium and frequently associated with E.coli infection. Histopathological interpretation may be difficult in the absence of the typical calcospherite bodies, as described by Michaelis-Gutmann. We thank Dr. David C. Utz for his valued consultation and the pathologists who reviewed the histological sections and confirmed the impression of malacoplakia in this case. REFERENCES T. E., BARE'l'A, J. ,,ND LAKE, G. C.: Malacoplakia; case involving bladder and one kidney and ureter. Urol. Inter., 1: 5-14,

GIBSON,

1955.

P. A.: Urological Pathology. Philadelphia: Lea & Febiger, vol. 1, pp. 215--217,

HERBUT,

1952.