Malakoplakia of testis

MALAKOPLAKIA

OF TESTIS

STEVEN Z. KLEINMAN, N. DAVID ROBINSON,

M.D. M.D.

STEVEN Miami

A. SIMON,

M.D.

Beach, Florida

ABSTRACT-Malakoplakia cases have been reverted.

A seventy-year-old white man was admitted to the hospital in April, 1981, after a three-day history of pain and swelling in the left testicle associated with high fever and dysuria. His left testicle was enlarged-approximately three times normal size, tender, with some involvement of the lower cord. Cefamandole nafate (Mandol) was started intravenously, but because of temperature elevation to 101 O F and persistence of swelling in his left testicle, tobramycin was added. Cultures of urine and blood showed no growth. Urinalysis showed 4 to 6 white blood cells and 1 to 3 red blood cells. Further evaluation included an intravenous pyelogram, testicular sonogram, and testicular scan. The testicular sonogram failed to demonstrate any discrete mass. The testicular scan showed increased perfusion to the left testicle compared with the right side, most consistent with an inflammatory process such as epididymitis or orchitis. The patient has mild signs of prostatism including nocturia ( x 2-3). The intravenous pyelogram showed partial duplication of the right collecting system and total duplication of the left collecting system. The prostate appeared enlarged and the bladder wall thickened and trabeculated. After a two-week hospital stay with no further fever or pain but with persistent testicular swelling the patient was discharged on a regimen of trimethoprim-sulfamethoxazole (Bactrim-DS). He was then followed as an

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in 1958. Since than 2zpproximately

of the testicle was first reported We add another case.

outpatient. Several weeks after was no decrease in the firmness therefore, the possibility existed lying cause might be a neoplasm cle. In June, 1981, the patient to the hospital for a left radical

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discharge, there of the testicle; that the underof the left testiwas readmitted orchiectomy.

Pathology The specimen was a slightly enlarged, moderately fir.m testis weighing 37 Gm and an attached, unremarkable segment of spermatic cord. The tunica albuginea was intact. Cut section revealed mottled, yellow-tan tissue separated by streaks of fibrous tissue replacing the testis (Fig. 1A). The seminiferous tubules could not be teased. On light microscopy the testicular architecture was effaced. Only the outlines of the seminiferous tubules remained. A granulomatous inflammation characterized by sheets of granular eosinophilic histiocytes containing solid or target-shaped calcospherites (MichaelisGutmann bodies) was present (Fig. 1B). The histiocytes contained PAS-positive cytoplasmic granules which resisted diastase digestion. The Michaelis-Gutmann bodies stained positively for calcium and iron. Electron ‘microscopy demonstrated characteristic Michaelis-Gutmann bodies with sharply circumscribed, electron-dense cores and paler outer zones containing particulate matter and

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FIGURE1. (A) G TOSSappearance of testicle; note streaks of fibrous tissue. (B) Malakoplakia: histiocytes with diagnostic Michaelis-Cutmann bodies. Some are solid (arrowhead), others are targetshaped (arrows). (Hematoxylin-eosin, high dry magnification.) (C) Electron microscopic appearance of Michaelis-Gutmann bodies. Round electrondense center surrounded by paler zone (arrow) with particulate matter (original magnification, X 25,300).

membrane fragments (Fig. 1C). Phagolysosomes containing lamellar and whorled structures were seen also.

ported the first caseof malakoplakia of the epididymis without testicular involvement. The fourteenth case report by Shaba and Black in 1971s was notable because no MichaelisGutmann bodies were seen, Approximately 25 casesof malakoplakia of the testis have been reported with involvement of the testis only, or the testis and epididymis.Q A recent case report by Saraf’Oinvolves both the testis and the prostate. Brown and Smith5 with their series of 8 patients found that malakoplakia of the testicle occurred in middle-aged men, with an age range of thirty-eight to sixty-two years. The mean age was 53.3 years. The right testicle was involved more frequently than the left. Caucasians were more frequently involved than blacks. Most of the patients were considered to have persisting orchitis, epididymitis, or epididymo-orchitis. Presenting symptoms and signs were acute onset presenting as testicular pain, swelling, tenderness, and sometimes chills and fever. In 7 of the patients an abscessof the involved testis developed, and thrombosed blood vessels were observed in 7. In most of the casesdefinitive orchiectomy has been required for diagnosis and/or cure.’ The differential diagnosis of

Comment Malakoplakia is a chronic granulomatous disease characterized by sheets of histiocytes and round calcified. structures (Michaelis-Gutmann bodies). It may involve any organ, but most frequently affects the genitourinary tract, gastrointestinal tract, and retroperitoneum. ls2Malakoplakia wa.s first described in 1902 by Michaelis and Gutmann and by von Hanseman in 1993.3 The clinical presentation of testicular malakoplakia includes acute onset of testicular pain, swelling, tenderness, and occasionally chills and fever. Of I53 cases of malakoplakia reviewed by Stanton and Maxted,l the testes were involved primarily in 12 per cent. The first caseof malakoplakia of the testicle was reported in 1958 by Haukohl and Chinchinian.3 Blackwell and Finley-Jones4 added a second case. Eight cases from the Armed Forces Institute of Pathology were reported by Brown and Smith in 1967.5 The eleventh and twelfth caseswere reported by Waisman and Rampton in 1968.s Green’ reUROLOGY

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TAHIX I.

Method Hematoxylin and eosin PAS with diastase Giemsa Sudan black (paraffin) Acid-fast Iron Autofluorescence (paraffin) Calcium Electron microscopy

‘Michaelis-Cutmann

Differential staining in conditions PAS-positive histiocytes

Malakoplakia

Whipple

Disease

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Granular Cell Tumor Eosinophilic

Ceroid Histiocytosis

Eosinophilic

Eosinophilic

Positive

Positive

Eosinophilic with golden brown Positive

Negative Negative

Negative Negative

Positive (sea blue) Positive

Negative Negative

Negative Positive (M-G* bodies)

Negative Negative

Positive Negative

Negative Negative

Negative

Negative

Golden yellow

Negative

Positive (M-G bodies)

Negative

Negative

Negative

Crystalline (M-G bodies) and osmophilic cytoplasmic granules

Bacilliform bodies

Osmophilic cystoplasmic granules

Meylin figuks, small and large lysosomal granules

bodies.

Source:

Amazon

K and Rywlin

-

Positive

AM.ls

and fungus diseaseneedsto be considered. Since, at present, testicular qnalakoplakia is not easily recognized or even considered in differential diagnosis, it is likely that many casesare being classified in a broad category of granulomatous orchitis.” Malakoplakia is generally considered to represent a chronic granulomatous inflammatory response to a gramnegative bacillus, particularly Escherichia coli or Aerobacter-Klebsiella species.eMacroscopitally, malakoplakia has a characteristic yellow, nodular appearance. 5 Microscopically, the Michaelis-Gutmann bodies are pathognomonic of malakoplakia. These are round to oval intracytoplasmic or extracellular bodies 3 to 5~ in diameter, hematoxylinophilic, and containing iron and calcium, and are chiefly located within large mononucleated cells. Histologic featureP of testicular malakoplakia, like those of lesions occurring in any other site, are characterized by closely packed, large macrophages, often of polyhedral configuration, with acidophilic cytoplasm (von Hanseman cells), in addition to inflammatory cell infiltration and fibrosis which usually characterize a nonspecific inflammatory process. MichaelisGutmann” bodies are found in the majority of cases of malakoplakia, but in some recorded casesthey were not described. neoplasm

associated with

In 1965 Smith13described a morphogenesisof urinary tract malakoplakia, consisting of three phases: early phase, classic or granulomatous phase, and fibrosing or healing phase. The early phase consists of plasma and Von Hansemann cells in an edematous connective tissue stroma. The classic or granulomatous phase consists of typical Michaelis-Gutmann bodies and large plump histiocytes, occasional giant cells, and a variable number of lymphocytes. The fibrosing or healing phase consists of fibroblasts and bundles of collagen around histiocytes with only occasional Michaelis-Gutmann bbdies. Michaelis-Gutmann bodies accdrding to Terner and Lattes14 are composed of a nonhuman glycolipid substancewhich could well represent remnants of the cell wall of enteric bacilli. Michaelis-Gutmann bodies have been found to be gram-negative, to stain positive with periodic acid Schiff and black with von Kossa.’ It is possible in early malakoplakia that Michaelis-Gutmann bodies may not be seen. In 1977 Abdou and associates15did in-depth immunologic

testing in a patient

with severe retro-

peritoneal malakoplakia who had positive eultures for E. coli. They found defects in blood monocytes including (1) decreased bactericidal activity to E. coli, (2) abnormally large lysosoma1 granules, (3) low levels of cyclic-guanine

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25 casesin the literature. Our patient, despite negative cultures, was treated with widespectrum antibiotics for left orchitis and epididymitis. The testicle remained hard, enlarged, and nontender two months after initial treatment despite continued use of antibiotics. The possibility of a neoplasm could not be excluded, and the patient finally underwent a left radical orchiectomy which revealed malakoplakia of the testicle.

monophosphate in the mononuclear cells, and (4) poor release of /3-glucuronidasefrom leukocytes on their exposure to opsonized zymosan particles. These defects could be corrected by cholinergic agonists such as carbachol in vitro or bethanechol in vivo. They used 40 mg of bethanechol chloride by mouth daily for one month. The pathologic processappearsto be an altered macrophage responseto E. coli.16 The causation is unclear, but E, coli infection can be identified in 75 per cent of cases.The basic defect is an abnormality of the bacteria-digesting function of tissue macrophages.17The granuloma is a secondary responseto a failure in the degradation of engulfed particles by phagocytes. The etiology and pathogenesis of malakoplakia are not well understood. However the most popular theory is a granulomatous reaction to gram-negative infection. This theory is supported by the electron microscopic findings of structures resembling gram-negative organisms and studies suggesting a variety of biochemical or phagocytic defects in histiocytes especially against E. coli. Malakoplakia is distinguished from granulomatous orchitis by the presenceof Michaelis-Gutmann bodies. These bodies are PAS positive and stain for calcium. The histiocytes of malakoplakia contain PAS-positive cytoplasmic granules which resist diastase digestion. These cytoplasmic granules may represent residual bodies (lysosomes containing breakdown products which cannot be further digested). The 14ichaelis-Gutmann bodies may represent a precipitate of calcium salts and other substances around a bacterial nidus within lysosomes. The differential diagnosis of large PAS-positive cells includes ceroid histiocytosis, Whipple disease,granular cell tumor, and malakoplakia. .A variety of additional special stains and clinical data may be required to differentiate these entities (Table I). Regarding therapy, Stanton and Maxted’ suggest a combination of an intracellularly active antibiotic to which the organism is sensitive, such as one of the sulfonamides, trimethoprim-sulfamethoxazole, or rifampin in conjunction with bethanechol and ascorbic acid. In summary, ‘we report an additional caseof malakoplakia of the testis to the approximately

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Suite 1020 1688Meridian Avenue Miami Beach, Florida 33139 (DR. KLEINMAN) References 1. Stanton M, and Maxted H: Malakoplakia: a study of the literature and current concepts of pathogenesis, diagnosis and treatment, J Urol 125: 139 (1981). 2. Rywlin AM, Ravel R, and Horwitz A: Malakoplakia of the colon, Am J Dig Dis 14: 491 (1969). 3. Haukohl R, and Chinchinian H: Malakoplakia of the testicle, Am J Clin Path01 29: 473 (1958). 4. Blackwell JB, and Finley-Jones JR: Malakoplakia of the testis, J Path01 Bacterial 78: 571 (1959). 5. Brown R, and Smith B: Malakoplakia of the testis, Am J Clin Path01 47: 135 (1967). 6. Waisman J, and Rampton JB: Malakoplakia of the testis and epididymis, Arch Path01 86: 43i (1968). 7. Green W: Malakonlakia of the enididvmis fwithout testicu’ ’ lar involvement), ibid sb: 138 (1968).& 8. Shaba J, and Black WA: Malakoplakia granuloma of the testis, J Urol 105: 687 (1971). 9. McClure J: Malakoplakia of the testis and its relationship to granulomatous orchitis, Am J Clin Path01 33: 670 (1980). 10. Saraf P: Malakoplakia case reported that involves testis, prostate, Urology Times, p 23, February, 1982. 11. Dionne GP, Bovill MD, and Seemayer TA: New fine structural observations in testicular malakoplakia, Urology 5: 828 (1975). 12. Tamura H, and Iannetti H: Ultrastructure of MichaelisGutmann body, study of a case of testicular malakoplakia, Arch Path01 98: 413 (1974). 13. Smith BH: Malakoplakia of urinary tract: a study of 24 cases, Am J Clin Path01 43: 409 (1965). 14. Terner JY, and Lattes R: Malakoplakia of colon and retroperitoneum: report of a case with histochemical study of the Michaelis-Gutmann inclusion bodies, ibid 44: 20 (1965): 15. Abdou N. et al: Malakodakia: evidence for monocvte lvsosomal abnormahty correctableby cholinergic agonist in vitro and in vivo, N Engl J Med 297: 1413 (1977). 16. Konnak JW: Malacoplakia of the Bladder, in Kaufman J (Ed): Current Urologic Therapy, Philadelphia, W! B. Saunders Company, 1980, p 221. 17. Maderazo E, Berlin BB, and Mohardt MD: Treatment of malakoplakia with trimethoprim-sulfamethoxazole, Urology 13:

70 (1979). 18. Amazon K, and Rywlin AM: Ceroid granulomas ovarian cyst, South Med J 73: 1067 (1980).

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