- Email: [email protected]
Renal malacoplakia
Magnetic Resonance Imaging 20 (2002) 611-614
Renal malacoplakia: demonstration by MR imaging Olga G. Ziminaa, Svetlana Rezuna, Diane Armaob, Larissa Bragab,1, Richard C. Semelkab,* b
a Department of Radiology, Cancer Research Center, Moscow, Russia Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Received 3 March 2002; accepted 30 May 2002
Abstract We report herein a case of histologically verified bilateral renal malacoplakia. MRI features were distinctive and include multiple nodules 1–2 cm in diameter that were low in signal on T1, T2 and early and late post gadolinium images with intervening fibrous stroma. Demonstration of renal malacoplakia on MR images may obviate the need for major surgery and rapidly direct patients to appropriate antimicrobial therapy for treatment. © 2002 Elsevier Science Inc. All rights reserved. Keywords: Kidneys; Malacoplakia; Chronic inflammatory disease; Magnetic resonance imaging; Disease course; Immunosuppression; Prognosis
1. Introduction Malacoplakia is a rare, chronic inflammatory disease predominantly affecting the bladder and occurring only occasionally in other organs including the kidney, skin, testis and gastrointestinal tract [1]. Isolated renal parenchymal involvement occurs in 16% of all cases [2]. Renal malacoplakia is associated with recurrent urinary tract infections [3]. Many patients with malacoplakia have underlying immunodeficiency or debility, including pharmacologic immunosuppression following transplantation. Of over 60 cases of renal malacoplakia reported in the literature, 75% have shown a multifocal pattern with bilateral disease in half of these cases [4]. To the best of our knowledge only a single paper has described the MRI findings of bilateral renal malacoplakia [5]. In the past, nephrectomy with histopathologic diagnosis was the mainstay of treatment for renal malacoplakia due to the rarity of the disease, its non-specific tumor-like appearance on radiologic studies and the lack of therapeutic options [6]. With recent advances in imaging, we believe that MR may be able to reliably distinguish renal malacoplakia from malignant masses and other tubulointerstitial disorders. We herein describe one case of malacoplakia which shows distinctive
* Corresponding author. Tel.: ⫹1-919-966-6777; fax: ⫹1-919-9669677. E-mail address: [email protected] (R.C. Semelka). 1 Supported by CAPES, Brasil.
features on MRI and review the appearance described in a prior report [5].
2. Materials and methods The MR examination was conducted on a 1.5 T MR image (VISION, Siemens Medical Systems, Iselin, NJ). The following MR sequences were employed: T2-weighted single-shot echo-train spin-echo (SS-ETSE; TR ⫽ infinity/ TE ⫽ 90; Flip angle ⫽ 150°); T1-weighted magnetization prepared gradient-echo images (Single-shot TR ⫽ 5/TE ⫽ 4; 180° preparation pulse); Fat suppressed spoiled gradientecho images with the same parameters. Gadolinium chelate (Magnevist, Berlex, Wayne, NJ, USA) was administered as a rapid bolus in a dosage of 0.1 mmol/Kg. Magnetization prepared gradient-echo images were repeated immediately after contrast administration, at 45 s and 1 min. Slice thickness was 8 –10 mm and field-of-view (FOV) was 300 –350 mm in all studies. Morphologic abnormalities, signal intensity, and enhancement features were evaluated.
3. Case report A 49-year-old African-American woman was admitted after a several week history of flank pain and malaise. Past medical history was significant for alcohol dependence and chronic pancreatitis. Clinical workup revealed hematuria, proteinuria, pyuria, elevated albumin and an elevated serum
0730-725X/02/$ – see front matter © 2002 Elsevier Science Inc. All rights reserved. PII: S 0 7 3 0 - 7 2 5 X ( 0 2 ) 0 0 5 2 0 - 9
612
O.G. Zimina et al. / Magnetic Resonance Imaging 20 (2002) 611-614
Fig. 1. Coronal (a) and transverse (b) SS-ETSE, transverse SGE (c) immediate post gadolinium SGE (d) and 1 min post gadolinium SGE (e). The kidneys are enlarged, irregularly contoured with ill define nodules that are low signal on T1-, T2-, early and late post gadolinium images. Ill defined nodules measuring 1 to 2 cm are subtended by fibrous septations, which are demonstrated as high signal on the T2-weighted images (a,b), low signal on pre gadolinium image (c), negligible enhancement immediately post gadolinium image (d) and exhibit pronounced enhancement on late post gadolinium image (arrow, e). Cortico-medullary differentiation is not present on early image (d).
creatinine, reaching 6.7 mg/dl, for which she was placed on hemodialysis. Therapy was instituted for culture positive E. coli urinary tract infection/bacteremia. Renal ultrasound revealed bilateral kidney enlargement up to 15 cm. No hydronephosis or renal calculi were visualized. The kidneys showed normal reniform contours and cortical echogenicity. The patient was then referred to MRI.
MR study showed enlarged, irregularly contoured kidneys with a striking multinodular appearance. Nodules were characterized as ill-defined masses measuring 1–2 cm in diameter that were mildly low in signal intensity on T1-weighted, T2weighted and early and late post-gadolinium images (Fig. 1). Slender bands of intervening fibrous tissue demonstrated mild high signal on T2-weighted images, low signal on T1-weighted
O.G. Zimina et al. / Magnetic Resonance Imaging 20 (2002) 611-614
images and showed negligible early enhancement and more pronounced enhancement on late post gadolinium images. Lack of cortico-medullary differentiation was noted during the arterial phase of contrast enhancement. This reflected the extensive nature of the disease process. No urinary obstruction or lymphadenopathy were present. Work up for the patient’s renal failure showed a monoclonal gammapathy of undetermined significance (MGUS). Renal biopsy was interpreted as histopathologic changes most consistent with malacoplakia. The patient was given a six week course of oral Ciprofloxacin together with Vitamin C and Bethanechol. A salutary therapeutic response was reflected in decreased serum creatinine to normal baseline levels. Urine culture revealed only mixed urogenital flora. Hemodialysis was discontinued. Follow up renal ultrasound revealed normalization of kidney size to 10 to 11 cm. Normal echogenicity was noted. The patients’ renal function remains stable, with no indication of urinary tract infection six months after cessation of Ciprofloxacin therapy.
4. Discussion Malacoplakia is a rare chronic inflammatory disorder, the first report published in 1902 by Michaelis and Gutmann [7]. The designation “malacoplakia” is derived from the Greek words “malakos” (soft) and “plakos” (plaques). Renal malacoplakia usually affects woman over 40 years of age with a clinical history of recurrent urinary tract infections [8]. E. coli is the most common pathogen [8]. Approximately 20% of patients have an associated immunocompromised state [9]. Patients with renal involvement by malacoplakia may present with fatigue, fever, flank pain, hematuria, pyuria or a palpable mass. Acute renal failure or rapid deterioration of pre-existent compromised renal function is not uncommon [10]. Bilateral renal malacoplakia has been associated with high mortality [4]. More recently, outcome has improved due to advances in antibiotic therapy [4]. Previously, the clinical presentation and radiologic appearance of renal malacoplakia often simulated a neoplasm, notably renal cell carcinoma. Ultrasound (US) and Computed tomography (CT) findings are generally non-specific. On US images, the most common features of renal malacoplakia is diffuse enlargement of affected kidneys. Less frequently detected are hypoechoic lesions, distortion of parenchymal contour and increased echogenicity of the parenchyma [6]. On CT images, nephromegaly and parenchymal inhomogeneity are the most typical findings [6]. The MRI findings in our case were distinctive, and appeared virtually identical to the previously reported MR study on a patient with bilateral malacoplakia [5], showing multiple 1–2 cm low signal nodules on all sequences with intervening fibrous stroma. In our experience, based on the MR appearance, the two most important entities in the differential diagnosis of renal malacoplakia are lymphoma and post-transplant lymphoproliferative disorder (PTLPD). In the vast majority of
613
cases, renal cell carcinoma and metastatic lesions appear substantially different on MR images, and are of secondary consideration. Patient history is also an important exclusionary factor with metastatic disease. An important distinction between the multifocal form of renal lymphoma [11] and malacoplakia is the presence of lymphadenopathy or disseminated disease observed in the former disease. We have also not observed such extensive nodular involvement with lymphoma as found in our case of malacoplakia. PTLPD is a morphologically heterogeneous group of diseases ranging from lymphatic hyperplasias to malignant lymphomas which develop after transplantation. Post-transplantation lymphomas involve renal allografts in approximately one-third of instances [12]. One previously reported case of PTLPD cited CT findings of multiple heterogeneous nodules in the renal allograft of a kidney transplant patient [13]. Renal malacoplakia is also associated with post transplant immunosuppression, with at least 19 renal transplant recipients reported to have developed malacoplakia in the allograft or at other sites [14]. Our experience with PTLPD of the kidneys is limited so, at present, we are unsure if the nodules in PTLPD are distinguishable from the nodules of malacoplakia. As present, both renal malacoplakia and PTLPD should be considered in the clinical setting of a patient with iatrogenic immunosuppression following organ transplantation showing radiologic evidence of a multinodular lesions in the kidney. In renal malacoplakia, gross examination displays an enlarged kidney with a smoothly bosselated surface. The cortex is expanded by homogeneous, soft-yellow nodules which bulge from the cut surface. Nodules may show an umbilicated, necrotic center. The disease process often extends into the medulla and effaces the corticomedullary junction. Ischemic necrosis of papillae is sometimes present [10]. Fibrosis may be a prominent feature [15]. Microscopic inspection discloses dense aggregates of plump, foamy macrophages, many of which contain the pathognomonic inclusion of malacoplakia, namely Michaelis-Gutmann bodies. Special stains for calcium and iron enhance the laminated, “target-like” appearance of these intracellular inclusions and demonstrate their mineralized nature. Biochemical analysis of inclusions has revealed an organic component, possibly of bacterial origin [16]. Scattered lymphocytes, plasma cells and fibrosis speak to the chronic inflammatory nature of the disorder. The precise pathogenesis of malacoplakia is unclear. Most experts agree that the disease is caused by a defect in macrophage function with impairment of bacteriocidal activity of monocytes/macrophages for Gram-negative organisms, especially E. coli [17]. The normal progression of lysosomes to phagolysosomes, with subsequent bacterial degradation and end product extrusion into the extracellular space, is delayed [1]. This functional abnormality has been ascribed to low levels of cyclic guanosine monophosphate (cGMP) [18]. Reduced cGMP levels impair microtubule assembly and -glucuronidase release, thus impairing
614
O.G. Zimina et al. / Magnetic Resonance Imaging 20 (2002) 611-614
phagolysome digestion of bacterial components [19]. Presumably, Michaelis-Gutmann bodies result from continued abnormal deposition of calcium phosphate and iron onto a matrix of incompletely digested bacterial components within overloaded phagolysosomes. Underlying immunodeficiency or debility have been cited as an accompanying secondary factor associated with altered reactivity of macrophages and lysosomal aberrations. The occurrence of malacoplakia in immunocompromised states are well documented and include such conditions as malignant neoplasms, systemic lupus erythematosis, tuberculosis, sarcoidosis and diabetes mellitus [20]. Ethanol abuse, as observed in our patient, and pharmacologic immunosuppression are also associated with renal malacoplakia. Renal malacoplakia is a highly treatable disease when detected in its early stages. In recent years, despite the limitations of US and CT, fine needle aspiration has been valuable in diagnosing the disease [19]. Successful medical management has been reported with antimicrobial agents capable of entering leukocytes and assisting in intracellular killing of bacterial. [4,19]. Effective antibiotics include Rifampin, Trimethoprim-Sulfamethoxazole and Ciprofloxacin [6,19]. Cholinergic agents such as bethanecol and ascorbic acid have been used as adjuvant therapy due to their ability to increase intracellular cGMP levels and enhance bacteriocidal activity of monocytes [19]. If possible, immunosuppressive drugs should be discontinued [3]. In summary, renal malacoplakia is a rare inflammatory disorder with morphologic and functional manifestations pointing to both microbiologic and host factors. In the past, the rarity of renal malacoplakia, its difficult clinical diagnosis and non specific tumor-like radiologic findings made nephrectomy the only treatment option. Based on our case, and its virtually identical appearance to another reported case, we believe that malacoplakia may have a distinctive MR appearance. Recognition of this appearance may serve to increase the early recognition of malacoplakia and direct patients to minimally invasive procedures such as fine needle aspiration to confirm the diagnosis. References [1] Horeta J, Cana˜ s M, Munne´ A, Arumi M. Renal malakoplakia: report of a case with multifocal involvement. Ultrastructural Pathol 1997; 21:5 75– 85.
[2] Singh PB, Gupta RC, Dwivedi US, Rastogi BL. Renal parenchymal malakoplakia. Br J Urol 1989;63:99 –100. [3] Van der Voort PHJ, Tel Velden AM, Wassenaar RP, Silberbusch J. Malakoplakia: two case reports, and a comparison at treatment modalities based on literature review. Arch Intern Med 1996;156:577– 83. [4] Michell MA, Markovitz DM, Killen PD, Braun DK. Bilateral renal malakoplakia presenting as a fever of unknown origin: case report and review. Clin Infect Dis 1994;18:704 –18. [5] Kamishima T, Ito K, Awaya H, Mitchell DG. MR imaging of bilateral renal malakoplakia after liver transplantation. AJR Am J Roentgenol 2000;175:919 –20. [6] Venkatesh SK, Mehrotra N, Gujral RB. Sonographic findings in renal parenchymal malakoplakia. J Clin US 2000;28:353–7. [7] Hong JJ, Liao PL, Lin JL, Hsueh S, Huang CC. Bilateral renal malakoplakia presenting as hemolytic-uraemic syndrome. Nephrol Dial Transplant 1999;14:2206 –9. [8] Dobyan DC, Truong LD, Eknoyan G. Renal malakoplakia reappraised. Am J Kidney Dis 1993;22:243–52. [9] Muttarak M, Peh WCG, Thamprasert K. Renal malakoplakia: case report. Australasian Radiol 1999;43:405–7. [10] Esparza A, McKay D, Cronan J, Chazan J. Renal parenchymal malakoplakia: histologic spectrum and its relationship to megalocytic interstitial nephritis and xantogranulomatous pyelonephritis. Am J Surg Pathol 1989;13:225–36. [11] Semelka RC, Kelekis NL, Burdeny DA, Mitchell DG, Brown JJ, Siegelman E. Renal lymphoma: demonstration by MR imaging. AJR Am J Roentgenol 1995;166:823–7. [12] Cohen JI. Epstein-Barr virus lymphoproliferative disease associated with acquired immunodeficiency. Medicine 1991;70:137– 60. [13] Paiva A, Freitas L, Pratas J, Gomes H, Mota A, Adelino M, Furtado L. Post transplant lymphoproliferative disease. Nephrol Dial Transplant 1998;13:2968 –71. [14] Shabtai M, Anaise D, Frei L, Waltzer WC, Frischer ZI, Jao S, Miller F, Rapaport FT. Malakoplakia in renal transplantation: an expression of altered tissue reactivity under immunosuppression. Transplant Proc 1989;21(4):3725–7. [15] Ordon˜ es NG, Rosai J. In: Ackermans’ Surgical Pathology, 8th ed. Vol. 1. Philadelphia: Mosby, 1996. p. 1123. [16] Sterrett GF, Heenan PJ, Wyche P, Papadimitriou JM. Malakoplakia of the prostate: a morphological and biochemical study. Pathology 1975;7:139 – 47. [17] Van Crevel R, Curfs J, Van der Ven AJM, Assmain K, Meis JFGM, Van der Meer JWM. Functional and morphological monocyte abnormalities in a patient with malakoplakia. Am J Med 1998;105:74 –7. [18] Olmo JMC, Carcamo P, De Iriarte EG, Jininez F, Martinez-Pineiro L, Martinez-Pineiro JA. Genitourinary malakoplakia. Br J Urol 1993; 72:6 –12. [19] Kapasi H, Robertson S, Futter N. Diagnosis of renal malakoplakia by fine needle aspiration cytology. Acta Cytologica 1998;42:1419 –23. [20] August C, Holzhausen HJ, Schro¨ der S. Renal parenchymal malakoplakia: ultrastructural findings in different stages of morphogenesis. Ultrastructural Pathol 1994;18:483–91.
Renal malacoplakia: demonstration by MR imaging Olga G. Ziminaa, Svetlana Rezuna, Diane Armaob, Larissa Bragab,1, Richard C. Semelkab,* b
a Department of Radiology, Cancer Research Center, Moscow, Russia Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Received 3 March 2002; accepted 30 May 2002
Abstract We report herein a case of histologically verified bilateral renal malacoplakia. MRI features were distinctive and include multiple nodules 1–2 cm in diameter that were low in signal on T1, T2 and early and late post gadolinium images with intervening fibrous stroma. Demonstration of renal malacoplakia on MR images may obviate the need for major surgery and rapidly direct patients to appropriate antimicrobial therapy for treatment. © 2002 Elsevier Science Inc. All rights reserved. Keywords: Kidneys; Malacoplakia; Chronic inflammatory disease; Magnetic resonance imaging; Disease course; Immunosuppression; Prognosis
1. Introduction Malacoplakia is a rare, chronic inflammatory disease predominantly affecting the bladder and occurring only occasionally in other organs including the kidney, skin, testis and gastrointestinal tract [1]. Isolated renal parenchymal involvement occurs in 16% of all cases [2]. Renal malacoplakia is associated with recurrent urinary tract infections [3]. Many patients with malacoplakia have underlying immunodeficiency or debility, including pharmacologic immunosuppression following transplantation. Of over 60 cases of renal malacoplakia reported in the literature, 75% have shown a multifocal pattern with bilateral disease in half of these cases [4]. To the best of our knowledge only a single paper has described the MRI findings of bilateral renal malacoplakia [5]. In the past, nephrectomy with histopathologic diagnosis was the mainstay of treatment for renal malacoplakia due to the rarity of the disease, its non-specific tumor-like appearance on radiologic studies and the lack of therapeutic options [6]. With recent advances in imaging, we believe that MR may be able to reliably distinguish renal malacoplakia from malignant masses and other tubulointerstitial disorders. We herein describe one case of malacoplakia which shows distinctive
* Corresponding author. Tel.: ⫹1-919-966-6777; fax: ⫹1-919-9669677. E-mail address: [email protected] (R.C. Semelka). 1 Supported by CAPES, Brasil.
features on MRI and review the appearance described in a prior report [5].
2. Materials and methods The MR examination was conducted on a 1.5 T MR image (VISION, Siemens Medical Systems, Iselin, NJ). The following MR sequences were employed: T2-weighted single-shot echo-train spin-echo (SS-ETSE; TR ⫽ infinity/ TE ⫽ 90; Flip angle ⫽ 150°); T1-weighted magnetization prepared gradient-echo images (Single-shot TR ⫽ 5/TE ⫽ 4; 180° preparation pulse); Fat suppressed spoiled gradientecho images with the same parameters. Gadolinium chelate (Magnevist, Berlex, Wayne, NJ, USA) was administered as a rapid bolus in a dosage of 0.1 mmol/Kg. Magnetization prepared gradient-echo images were repeated immediately after contrast administration, at 45 s and 1 min. Slice thickness was 8 –10 mm and field-of-view (FOV) was 300 –350 mm in all studies. Morphologic abnormalities, signal intensity, and enhancement features were evaluated.
3. Case report A 49-year-old African-American woman was admitted after a several week history of flank pain and malaise. Past medical history was significant for alcohol dependence and chronic pancreatitis. Clinical workup revealed hematuria, proteinuria, pyuria, elevated albumin and an elevated serum
0730-725X/02/$ – see front matter © 2002 Elsevier Science Inc. All rights reserved. PII: S 0 7 3 0 - 7 2 5 X ( 0 2 ) 0 0 5 2 0 - 9
612
O.G. Zimina et al. / Magnetic Resonance Imaging 20 (2002) 611-614
Fig. 1. Coronal (a) and transverse (b) SS-ETSE, transverse SGE (c) immediate post gadolinium SGE (d) and 1 min post gadolinium SGE (e). The kidneys are enlarged, irregularly contoured with ill define nodules that are low signal on T1-, T2-, early and late post gadolinium images. Ill defined nodules measuring 1 to 2 cm are subtended by fibrous septations, which are demonstrated as high signal on the T2-weighted images (a,b), low signal on pre gadolinium image (c), negligible enhancement immediately post gadolinium image (d) and exhibit pronounced enhancement on late post gadolinium image (arrow, e). Cortico-medullary differentiation is not present on early image (d).
creatinine, reaching 6.7 mg/dl, for which she was placed on hemodialysis. Therapy was instituted for culture positive E. coli urinary tract infection/bacteremia. Renal ultrasound revealed bilateral kidney enlargement up to 15 cm. No hydronephosis or renal calculi were visualized. The kidneys showed normal reniform contours and cortical echogenicity. The patient was then referred to MRI.
MR study showed enlarged, irregularly contoured kidneys with a striking multinodular appearance. Nodules were characterized as ill-defined masses measuring 1–2 cm in diameter that were mildly low in signal intensity on T1-weighted, T2weighted and early and late post-gadolinium images (Fig. 1). Slender bands of intervening fibrous tissue demonstrated mild high signal on T2-weighted images, low signal on T1-weighted
O.G. Zimina et al. / Magnetic Resonance Imaging 20 (2002) 611-614
images and showed negligible early enhancement and more pronounced enhancement on late post gadolinium images. Lack of cortico-medullary differentiation was noted during the arterial phase of contrast enhancement. This reflected the extensive nature of the disease process. No urinary obstruction or lymphadenopathy were present. Work up for the patient’s renal failure showed a monoclonal gammapathy of undetermined significance (MGUS). Renal biopsy was interpreted as histopathologic changes most consistent with malacoplakia. The patient was given a six week course of oral Ciprofloxacin together with Vitamin C and Bethanechol. A salutary therapeutic response was reflected in decreased serum creatinine to normal baseline levels. Urine culture revealed only mixed urogenital flora. Hemodialysis was discontinued. Follow up renal ultrasound revealed normalization of kidney size to 10 to 11 cm. Normal echogenicity was noted. The patients’ renal function remains stable, with no indication of urinary tract infection six months after cessation of Ciprofloxacin therapy.
4. Discussion Malacoplakia is a rare chronic inflammatory disorder, the first report published in 1902 by Michaelis and Gutmann [7]. The designation “malacoplakia” is derived from the Greek words “malakos” (soft) and “plakos” (plaques). Renal malacoplakia usually affects woman over 40 years of age with a clinical history of recurrent urinary tract infections [8]. E. coli is the most common pathogen [8]. Approximately 20% of patients have an associated immunocompromised state [9]. Patients with renal involvement by malacoplakia may present with fatigue, fever, flank pain, hematuria, pyuria or a palpable mass. Acute renal failure or rapid deterioration of pre-existent compromised renal function is not uncommon [10]. Bilateral renal malacoplakia has been associated with high mortality [4]. More recently, outcome has improved due to advances in antibiotic therapy [4]. Previously, the clinical presentation and radiologic appearance of renal malacoplakia often simulated a neoplasm, notably renal cell carcinoma. Ultrasound (US) and Computed tomography (CT) findings are generally non-specific. On US images, the most common features of renal malacoplakia is diffuse enlargement of affected kidneys. Less frequently detected are hypoechoic lesions, distortion of parenchymal contour and increased echogenicity of the parenchyma [6]. On CT images, nephromegaly and parenchymal inhomogeneity are the most typical findings [6]. The MRI findings in our case were distinctive, and appeared virtually identical to the previously reported MR study on a patient with bilateral malacoplakia [5], showing multiple 1–2 cm low signal nodules on all sequences with intervening fibrous stroma. In our experience, based on the MR appearance, the two most important entities in the differential diagnosis of renal malacoplakia are lymphoma and post-transplant lymphoproliferative disorder (PTLPD). In the vast majority of
613
cases, renal cell carcinoma and metastatic lesions appear substantially different on MR images, and are of secondary consideration. Patient history is also an important exclusionary factor with metastatic disease. An important distinction between the multifocal form of renal lymphoma [11] and malacoplakia is the presence of lymphadenopathy or disseminated disease observed in the former disease. We have also not observed such extensive nodular involvement with lymphoma as found in our case of malacoplakia. PTLPD is a morphologically heterogeneous group of diseases ranging from lymphatic hyperplasias to malignant lymphomas which develop after transplantation. Post-transplantation lymphomas involve renal allografts in approximately one-third of instances [12]. One previously reported case of PTLPD cited CT findings of multiple heterogeneous nodules in the renal allograft of a kidney transplant patient [13]. Renal malacoplakia is also associated with post transplant immunosuppression, with at least 19 renal transplant recipients reported to have developed malacoplakia in the allograft or at other sites [14]. Our experience with PTLPD of the kidneys is limited so, at present, we are unsure if the nodules in PTLPD are distinguishable from the nodules of malacoplakia. As present, both renal malacoplakia and PTLPD should be considered in the clinical setting of a patient with iatrogenic immunosuppression following organ transplantation showing radiologic evidence of a multinodular lesions in the kidney. In renal malacoplakia, gross examination displays an enlarged kidney with a smoothly bosselated surface. The cortex is expanded by homogeneous, soft-yellow nodules which bulge from the cut surface. Nodules may show an umbilicated, necrotic center. The disease process often extends into the medulla and effaces the corticomedullary junction. Ischemic necrosis of papillae is sometimes present [10]. Fibrosis may be a prominent feature [15]. Microscopic inspection discloses dense aggregates of plump, foamy macrophages, many of which contain the pathognomonic inclusion of malacoplakia, namely Michaelis-Gutmann bodies. Special stains for calcium and iron enhance the laminated, “target-like” appearance of these intracellular inclusions and demonstrate their mineralized nature. Biochemical analysis of inclusions has revealed an organic component, possibly of bacterial origin [16]. Scattered lymphocytes, plasma cells and fibrosis speak to the chronic inflammatory nature of the disorder. The precise pathogenesis of malacoplakia is unclear. Most experts agree that the disease is caused by a defect in macrophage function with impairment of bacteriocidal activity of monocytes/macrophages for Gram-negative organisms, especially E. coli [17]. The normal progression of lysosomes to phagolysosomes, with subsequent bacterial degradation and end product extrusion into the extracellular space, is delayed [1]. This functional abnormality has been ascribed to low levels of cyclic guanosine monophosphate (cGMP) [18]. Reduced cGMP levels impair microtubule assembly and -glucuronidase release, thus impairing
614
O.G. Zimina et al. / Magnetic Resonance Imaging 20 (2002) 611-614
phagolysome digestion of bacterial components [19]. Presumably, Michaelis-Gutmann bodies result from continued abnormal deposition of calcium phosphate and iron onto a matrix of incompletely digested bacterial components within overloaded phagolysosomes. Underlying immunodeficiency or debility have been cited as an accompanying secondary factor associated with altered reactivity of macrophages and lysosomal aberrations. The occurrence of malacoplakia in immunocompromised states are well documented and include such conditions as malignant neoplasms, systemic lupus erythematosis, tuberculosis, sarcoidosis and diabetes mellitus [20]. Ethanol abuse, as observed in our patient, and pharmacologic immunosuppression are also associated with renal malacoplakia. Renal malacoplakia is a highly treatable disease when detected in its early stages. In recent years, despite the limitations of US and CT, fine needle aspiration has been valuable in diagnosing the disease [19]. Successful medical management has been reported with antimicrobial agents capable of entering leukocytes and assisting in intracellular killing of bacterial. [4,19]. Effective antibiotics include Rifampin, Trimethoprim-Sulfamethoxazole and Ciprofloxacin [6,19]. Cholinergic agents such as bethanecol and ascorbic acid have been used as adjuvant therapy due to their ability to increase intracellular cGMP levels and enhance bacteriocidal activity of monocytes [19]. If possible, immunosuppressive drugs should be discontinued [3]. In summary, renal malacoplakia is a rare inflammatory disorder with morphologic and functional manifestations pointing to both microbiologic and host factors. In the past, the rarity of renal malacoplakia, its difficult clinical diagnosis and non specific tumor-like radiologic findings made nephrectomy the only treatment option. Based on our case, and its virtually identical appearance to another reported case, we believe that malacoplakia may have a distinctive MR appearance. Recognition of this appearance may serve to increase the early recognition of malacoplakia and direct patients to minimally invasive procedures such as fine needle aspiration to confirm the diagnosis. References [1] Horeta J, Cana˜ s M, Munne´ A, Arumi M. Renal malakoplakia: report of a case with multifocal involvement. Ultrastructural Pathol 1997; 21:5 75– 85.
[2] Singh PB, Gupta RC, Dwivedi US, Rastogi BL. Renal parenchymal malakoplakia. Br J Urol 1989;63:99 –100. [3] Van der Voort PHJ, Tel Velden AM, Wassenaar RP, Silberbusch J. Malakoplakia: two case reports, and a comparison at treatment modalities based on literature review. Arch Intern Med 1996;156:577– 83. [4] Michell MA, Markovitz DM, Killen PD, Braun DK. Bilateral renal malakoplakia presenting as a fever of unknown origin: case report and review. Clin Infect Dis 1994;18:704 –18. [5] Kamishima T, Ito K, Awaya H, Mitchell DG. MR imaging of bilateral renal malakoplakia after liver transplantation. AJR Am J Roentgenol 2000;175:919 –20. [6] Venkatesh SK, Mehrotra N, Gujral RB. Sonographic findings in renal parenchymal malakoplakia. J Clin US 2000;28:353–7. [7] Hong JJ, Liao PL, Lin JL, Hsueh S, Huang CC. Bilateral renal malakoplakia presenting as hemolytic-uraemic syndrome. Nephrol Dial Transplant 1999;14:2206 –9. [8] Dobyan DC, Truong LD, Eknoyan G. Renal malakoplakia reappraised. Am J Kidney Dis 1993;22:243–52. [9] Muttarak M, Peh WCG, Thamprasert K. Renal malakoplakia: case report. Australasian Radiol 1999;43:405–7. [10] Esparza A, McKay D, Cronan J, Chazan J. Renal parenchymal malakoplakia: histologic spectrum and its relationship to megalocytic interstitial nephritis and xantogranulomatous pyelonephritis. Am J Surg Pathol 1989;13:225–36. [11] Semelka RC, Kelekis NL, Burdeny DA, Mitchell DG, Brown JJ, Siegelman E. Renal lymphoma: demonstration by MR imaging. AJR Am J Roentgenol 1995;166:823–7. [12] Cohen JI. Epstein-Barr virus lymphoproliferative disease associated with acquired immunodeficiency. Medicine 1991;70:137– 60. [13] Paiva A, Freitas L, Pratas J, Gomes H, Mota A, Adelino M, Furtado L. Post transplant lymphoproliferative disease. Nephrol Dial Transplant 1998;13:2968 –71. [14] Shabtai M, Anaise D, Frei L, Waltzer WC, Frischer ZI, Jao S, Miller F, Rapaport FT. Malakoplakia in renal transplantation: an expression of altered tissue reactivity under immunosuppression. Transplant Proc 1989;21(4):3725–7. [15] Ordon˜ es NG, Rosai J. In: Ackermans’ Surgical Pathology, 8th ed. Vol. 1. Philadelphia: Mosby, 1996. p. 1123. [16] Sterrett GF, Heenan PJ, Wyche P, Papadimitriou JM. Malakoplakia of the prostate: a morphological and biochemical study. Pathology 1975;7:139 – 47. [17] Van Crevel R, Curfs J, Van der Ven AJM, Assmain K, Meis JFGM, Van der Meer JWM. Functional and morphological monocyte abnormalities in a patient with malakoplakia. Am J Med 1998;105:74 –7. [18] Olmo JMC, Carcamo P, De Iriarte EG, Jininez F, Martinez-Pineiro L, Martinez-Pineiro JA. Genitourinary malakoplakia. Br J Urol 1993; 72:6 –12. [19] Kapasi H, Robertson S, Futter N. Diagnosis of renal malakoplakia by fine needle aspiration cytology. Acta Cytologica 1998;42:1419 –23. [20] August C, Holzhausen HJ, Schro¨ der S. Renal parenchymal malakoplakia: ultrastructural findings in different stages of morphogenesis. Ultrastructural Pathol 1994;18:483–91.