Renal parenchymal malacoplakia: a different stage of xanthogranulomatous pyelonephritis?

Journal of Pediatric Surgery (2007) 42, E35–E38

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Renal parenchymal malacoplakia: a different stage of xanthogranulomatous pyelonephritis? Murat Yiğiter a , Dilek İlgici b , Mustafa Çelik a , İrfan Serdar Arda a,⁎, Akgün Hiçsönmez a a

Department of Pediatric Surgery, Baskent University Faculty of Medicine, 06490 Bahçelievler Ankara, Turkey Department of Pathology, Baskent University Faculty of Medicine, 06490 Bahçelievler Ankara, Turkey

b

Index words: Malacoplakia; Renal malacoplakia; Xanthogranulomatous pyelonephritis; Children

Abstract Malacoplakia is a rare inflammatory condition characterized by demonstrative MichaelisGutmann bodies, which are foamy histiocytes with distinctive basophilic inclusions. Malacoplakia is caused by the inadequate elimination of bacteria by macrophages or monocytes as a result of defective phagocytic activity. Xanthogranulomatous pyelonephritis is characterized by the destruction of renal parenchyma and its replacement by solid sheets of foamy lipid-laden macrophages. Prolonged infection of the kidney, which is frequently caused by an obstruction of the urinary tract, is the pathologic mechanism of that condition. We present a 6-year-old patient with a poorly functioning kidney who had a prolonged recurrent urinary tract infection. The results of histologic analysis revealed an inflammatory infiltration consisting predominantly of foamy and epithelioid histiocytes that contained round intracytoplasmic concretions characteristic of Michaelis-Gutmann bodies. We suggest that malacoplakia might be a stage of xanthogranulomatous pyelonephritis. © 2007 Elsevier Inc. All rights reserved.

Malacoplakia (MKP) is a rare inflammatory condition that is manifested as plaque or a nodule that typically affects the genitourinary tract [1]. Malacoplakia usually occurs in immunocompromised or debilitated adults. It was first described in 1902 as a disorder characterized by yellow soft plaques on the mucosa of the urinary bladder [2]. Rarely, MKP affects the renal parenchyma. It is more common in adults and is very rare in children [3,4]. Malacoplakia is believed to result from the inadequate elimination of bacteria by macrophages or monocytes that exhibit defective phagolysosomal activity [5]. Many possible causes of MKP (prolonged treatment with ⁎ Corresponding author. Baskent University Faculty of Medicine, Department of Pediatric Surgery, Fevzi Cakmak Caddesi 10, Sokak No. 45, Bahçelievler Ankara, Turkey. Tel.: +90 312 215 72 28, +90 312 212 29 12; fax: +90 312 213 23 40, +90 312 223 73 33. E-mail address: [email protected] (İ.S. Arda). 0022-3468/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2007.05.005

systemic corticosteroids, tuberculosis, sarcoidosis, fungal or viral infection, and neoplasia) have been proposed [5]. Microscopically, this disorder is characterized by foamy histiocytes with distinctive basophilic inclusions (Michaelis-Gutmann bodies) [2]. Xanthogranulomatous pyelonephritis (XGP) is a rare but well-recognized morphological and clinical variant of chronic pyelonephritis that is characterized by the destruction of the renal parenchyma and its replacement by granulomatous tissue containing foamy lipid-laden macrophages [6]. It is a rare condition in children; fewer than 300 cases have been reported in the literature since 1960 [7]. Xanthogranulomatous pyelonephritis develops after a prolonged kidney infection in which the passage of urine is obstructed, usually by a stone. Although MKP and XGP have similar gross and morphological features, they differ in cause and histologic characteristics. We report an unusual form of renal MKP

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Fig. 1 Nephrectomy specimen with calyceal dilatation and parenchymal yellowish nodularity.

Fig. 3 Round intracytoplasmic concretions in the histiocytes (black arrows; hematoxylin and eosin, original magnification ×400).

that occurred in a 6-year-old patient with obstructive uropathy. The morphological features of this form of MKP (focal collections of foamy lipid-laden macrophages and clusters of distinct Michaelis-Gutmann bodies) were suggestive of XGP.

tions, and a few renal calculi, all of which are characteristics of XGP. The results of a technetium 99m diethylenetriamine pentaacetic acid split renal function test indicated that patient's left kidney function accounted for only approximately 5% of the patient's total renal function. Biochemical analysis showed no abnormality. Urinalysis revealed 22 white blood cells per high-powered field, but the result of a urine culture was negative. The results of immunologic studies were within normal limits for the patient's age. During surgery, the left kidney was found to be enlarged and was firmly adherent to the left colon and perirenal fascia. Nephroureterectomy was performed. The left ureter was filled with stones. In macroscopic evaluation, the kidney weighed 92 g, and moderate calyceal dilatation and calculi were noted. The capsule was adherent to (and was removed with difficulty from) the parenchyma. The renal surface was covered with granular scar tissue, and firm yellow nodules surrounded the calyces and parenchyma in its cut surface (Fig. 1). Microscopic examination revealed a granulomatous inflammatory infiltrate consisting primarily of foamy and epithelioid histiocytes, multinucleated giant cells, and a mixture of lymphocytes and plasma cells (Fig. 2). Some epithelioid histiocytes contained round intracytoplasmic concretions that were characteristic of Michaelis-Gutmann bodies (Fig. 3). They were better visualized with von Kossa's calcium stain (Fig. 4). A true granulomatous formation with both histiocytes and giant cells was noted, as was central necrosis in some areas. The result of a special stain for fungi and acid-fast organisms was negative. The patient was diagnosed as having MKP with clusters of MichaelisGutmann bodies.

1. Case report A 6-year-old girl was admitted to our institution with significantly decreased function of the left kidney. Her history was remarkable for recurrent urinary tract infections, and she had undergone surgery to treat left-sided pyonephrosis and urolithiasis a few months earlier. Physical examination revealed no abnormality. The results of renal ultrasonography showed a lobulated left kidney with multiple parenchymal hypoechogenic areas, an absence of normal parenchymal structures, perinephric thickening with multiple calcifica-

2. Discussion Fig. 2 Prominent foamy histiocytes admixed with mononuclear cells. Black arrows show foamy lipid laden histiocytes (hematoxylin and eosin, original magnification ×200).

Malacoplakia, which was originally described in the early 1900s, is an uncommon form of chronic inflammatory

Renal parenchymal malacoplakia

Fig. 4 White arrows show lamellar bodies containing iron and calcium (Michaelis-Gutmann bodies; von Kossa's calcium stain, original magnification ×400).

granulomatous disease with distinctive histologic features. The first pathologic descriptions of MKP were provided by Michaelis and Gutmann [2]. von Hansemann [8] introduced the term malacoplakia, which was derived from the Greek words malakos (soft) and plakos (plaque). Malacoplakia most frequently affects the urinary tract but has also been identified at other anatomical sites, including the genital tract, skin, retroperitoneum, lung, gastrointestinal tract, testis, thyroid, and bone [6]. The kidney is affected in only 15% of patients with MKP [9]. Patients with MKP usually have an underlying systemic disease such as systemic lupus erythematosus, diabetes mellitus, myotonic dystrophy, or chronic active hepatitis. Malacoplakia occurs infrequently in immunocompromised patients [10]. Gramnegative bacteria are most often associated with this disorder; Escherichia coli is found in more than two thirds of MKP lesions [1,3]. Malacoplakia that affects the genitourinary system is most common in middle-aged women (average age at onset, N50 years), and childhood renal MKP is a very rare condition. To our knowledge, fewer than 15 childhood cases of renal MKP have been reported in the English literature to date. The underlying abnormality in people with MKP seems to be a defective macrophage lysosomal digestion of phagocytosed bacteria (particularly coliform varieties). This results in the inadequate elimination of bacteria, which in turn leads to the accumulation of partially digested bacteria as a deposition of calcium and iron on residual bacterial glycolipid in monocytes or macrophages [1,5]. This resulting basophilic inclusion structure, which consists of the calcified products of phagocytized bacteria, is found in Michaelis-Gutmann bodies, the presence of which is pathognomonic for MKP [2,8,11]. Functional monocyte abnormalities are considered in the development of disease [12]. Studies suggest that a decreased proportion in the level of intracellular cyclic guanosine monophosphate and the level of cyclic adenosine monophosphate might be the cause

E37 of defective phagocytosis, which in turn causes incomplete bacterial digestion [13]. Malacoplakia is a histologic diagnosis. On gross examination, the lesions of MKP appear to be yellow-brown plaques or nodules that are sometimes umbilicated and are rarely ulcerated. Microscopically, the large macrophages with foamy eosinophilic cytoplasm that are present at sites of infection exhibit numerous secondary lysosomes (von Hansemann cells) that contain partially digested organisms. The fusion and calcification of these lysosomes result in the formation of intracytoplasmic crystalline bodies with a central hydroxyapatite core (Michaelis-Gutmann bodies). When examined via light microscopy, Michaelis-Gutmann bodies often have a targetoid appearance with a dense central core. That typical targetoid appearance may not be apparent if the plane of section does not pass through the dense central core. Michaelis-Gutmann bodies stain pale basophilic in hematoxylin-eosin–stained sections or when examined with periodic acid-Schiff and von Kossa's stains, but they are diastase resistant [14]. Microscopically, the lesion evolves through 3 phases [15]: an early phase that is characterized by plasma cells and histiocytes in the edematous stroma, a classic phase that is characterized by histiocytes containing Michaelis-Gutmann bodies and few lymphocytes and plasma cells, and a fibrosing phase that is characterized by fibroblasts and collagen that are found in well-defined bundles between the foci of the histiocytes, with occasional Michaelis-Gutmann bodies. The radiologic findings in patients with MKP are nonspecific. Most patients demonstrate renal enlargement, disorganization of the central echo, and complex and poor echogenicity of the kidney on ultrasonographic examination [16]. It has been reported that MKP may have distinct characteristics that, when detected via magnetic resonance imaging, obviate the need for major surgery [17]. Multifocal bacterial nephritis, xanthogranulomatous nephritis, lymphoma, and polycystic kidney disease may have characteristics similar to those of MKP. In recent years, the use of fine-needle aspiration biopsy has enabled the rapid and correct diagnosis of that disorder [18]. The treatment of renal MKP depends on the degree of kidney involvement. Improving immunodeficient states and administering antibiotics with high intracellular diffusion and activity and/or bethanechol chloride (urecholine), a cholinergic agonist that improves the bactericidal activity of monocytes against E coli, are medical treatment options. When there is a poor response to medical therapy, the surgical drainage of renal abscess or nephrectomy is mandatory. Xanthogranulomatous pyelonephritis is an uncommon chronic inflammatory renal disorder that is characterized by the destruction of the renal parenchyma and its replacement by solid sheets of foamy lipid-laden macrophages [5,19]. Xanthogranulomatous pyelonephritis develops during prolonged kidney infection when the passage of urine is obstructed, usually by a stone. Urinary tract infections with gram-negative bacteria, particularly Proteus species or

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E38 (next most frequently) E coli, are most commonly associated with XGP. This disorder often mimics neoplastic and other renal parenchymal and inflammatory diseases, which may result in misdiagnosis. Xanthogranulomatous pyelonephritis is classified as diffuse (92%) or focal (8%) [19]. It is further divided into 3 stages: stage 1 (nephric XGP, inflammation confined to the kidneys), stage 2 (perinephric XGP, inflammation involving the kidneys and perirenal fat), and stage 3 (paranephric XGP, inflammation involving the kidneys, perirenal fat, and retroperitoneum). Ultrasonographic studies are helpful in determining the site and size of a renal mass. In patients with XGP, enlargement of the entire kidney, multiple hypoechoic renal areas of calyceal dilatation and parenchymal destruction, and presence of perinephric fluid are often noted. Computed tomographic evaluations are sensitive in revealing intrarenal lesions such as calculi, areas of renal destruction, hydronephrosis, and abscesses [20]. The differential diagnosis of XGP includes neoplastic disorders such as Wilms tumor, neuroblastoma, leukemia, lymphoma, clear cell carcinoma, or retroperitoneal sarcoma, as well as inflammatory processes such as renal or perirenal abscess, pyonephrosis, renal tuberculosis, focal or diffuse nephritis, or fungal infection. The definitive diagnosis depends on the results of the examination of tissue obtained by percutaneous fine-needle aspiration or by surgery. Gross examination reveals a marked loss of renal parenchyma that has been replaced by yellow fatty tissue, with or without macroscopic focal abscesses. Microscopic examination shows a diffuse granulomatous inflammatory infiltrate that includes a large number of foamy histiocytes and some multinucleated giant cells, as well as lymphocytes, plasma cells, and neutrophils [14]. Renal parenchymal MKP and XGP are uncommon inflammatory conditions of the kidney with strikingly similar gross and morphological characteristics. Their clinical association with repeated urinary tract infections and tumor-like enlargement and deformity of the affected kidney has been established. Renal parenchymal MKP and XGP are characterized by a mixture of inflammatory cells in which histiocytes predominate. Although the cells specific for XGP are the foamy histiocytes, Michaelis-Gutmann bodies are identified only in cases of MKP. Unlike most adult patients with MKP, our patient had no malignancy, immunodeficiency syndrome, or autoimmune disease and had not been receiving steroids or immunosuppressive agents. She had experienced repeated urinary tract infections, pyonephrosis, and renal calculi. She demonstrated destructive and frankly granulomatous histologic findings with a preponderance of foamy histiocytes reminiscent of XGP and clusters of Michaelis-Gutmann bodies that produced a positive result

when stained with von Kossa's stain. We concluded that this patient exhibited an atypical histologic presentation of MKP with findings of XGP, and we suggest that MKP is a different stage or appearance of XGP.

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