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Malakoplakia of liver: Report of two cases Noha Botros a,∗ , Sen R. Yan b , Ian R. Wanless a a b
Department of Pathology, Dalhousie University, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia B3H 1V8, Canada Department of Pathology, Dr. Chalmers Regional Hospital, Fredericton, NB, Canada
a r t i c l e
i n f o
Article history: Received 25 April 2013 Received in revised form 5 December 2013 Accepted 12 March 2014 Keywords: Malakoplakia Liver Michaelis-Gutmann bodies
a b s t r a c t Malakoplakia is an unusual chronic inflammatory condition characterized by the presence of MichaelisGutmann bodies. Patients with malakoplakia often have an immunodeficiency state. It is believed that malakoplakia results from a defective macrophage response to phagocytosed bacteria. Malakoplakia most commonly affects the genitourinary tract. Cases confined to the liver are rare, with only five cases described in the literature. We report two cases of malakoplakia of liver; both were incidental autopsy findings. The first case involves a 53-year-old man with systemic lupus erythematosus and chronic refractory pancytopenia who presented with febrile neutropenia. His blood culture was positive for Stenotrophomonas maltophilia and Enterococcus faecium, and he subsequently developed invasive pulmonary aspergillosis. The second case involves a 60-year-old man who presented with a mass in periorbital tissue which, on biopsy, showed inflammation and Treponema-like spirochetes. He died unexpectedly at home. Autopsy revealed adrenal gland chronic inflammation and abscess. Both cases had grossly normal livers with microscopic findings of calcified targetoid structures consistent with Michaelis-Gutmann bodies. In these cases, malakoplakia was an incidental finding confined to liver. Although asymptomatic in these cases, diagnosis in the liver may be useful to initiate a search for hepatic or non-hepatic infections. © 2014 Elsevier GmbH. All rights reserved.
Introduction Malakoplakia is a distinctive inflammatory condition characterized by the presence of histiocytic cells with eosinophilic granular cytoplasm, often known as “von Hansemann’s histiocytes”, accompanied by the pathognomonic intracellular and extracellular siderocalcific Michaelis-Gutmann (MG) bodies [2]. The urinary bladder is the most common site of involvement. Malakoplakia of the liver is rare, with only five cases documented in the world literature [2,5,6,8,10]. We report two cases of liver malakoplakia. Both were incidental autopsy findings. Case reports Case 1 A 53-year-old man with chronic seizure disorder developed refractory pancytopenia associated with a monoclonal gammopathy. One year later, he had a complicated course with pneumonia
∗ Corresponding author. Tel.: +1 902 412 2683. E-mail address: [email protected] (N. Botros).
and probable viral encephalitis which was followed 3 months later with bilateral deep vein thrombosis and pulmonary embolism. Laboratory findings established a diagnosis of systemic lupus erythematosus, and he was started on steroids. Six months later, a renal biopsy was performed that showed membranous nephritis typical of lupus nephritis. He presented one week after the biopsy with rigors and urinary urgency. On admission, he was found to have severe febrile neutropenia. In the hospital, he had multiple recurrent febrile episodes, and blood culture was positive for Stenotrophomonas maltophilia and Enterococcus faecium. A bone marrow biopsy showed severe trilineage hypocellularity and abnormal lymphocytic infiltrate. Despite multiple courses of broad spectrum antibiotics and repeated blood transfusions, he developed progressive respiratory deterioration with bilateral pulmonary consolidation. He died of respiratory failure two weeks later. An autopsy was performed.
Case 2 A 60-year-old man presented with an acute vision problem. A CT scan showed a destructive bony process involving the lateral wall of the left orbit and sphenoid bone, which was clinically suspicious for malignancy. Biopsy of the lesion showed destructive inflammatory
http://dx.doi.org/10.1016/j.prp.2014.03.004 0344-0338/© 2014 Elsevier GmbH. All rights reserved.
Please cite this article in press as: N. Botros, et al., Malakoplakia of liver: Report of two cases, Pathol. – Res. Pract (2014), http://dx.doi.org/10.1016/j.prp.2014.03.004
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process involving bone, skeletal muscle and lacrimal gland. Plasma cells, macrophages and numerous neutrophilic microabscesses were seen. Scattered Treponema-like spirochetes were identified on Steiner stain. The biopsy findings were highly suggestive of a gummatous lesion of syphilis. He died unexpectedly at home, and an autopsy was done. Pathologic findings Case 1 Autopsy showed invasive pulmonary aspergillosis with extensive fungal colonization of both lungs. Features included diffuse alveolar damage, fungal invasion of vessel walls, thrombosis, and infarcts. The liver was grossly normal with incidental microscopic findings of mild portal lymphoid and macrophage infiltration without significant fibrosis (Fig. 1). There were multiple, small round to oval,
calcified bodies (calcospherites) located within portal interstitium and sinusoids. The bodies were either intracellular or extracellular. Many of the bodies were confirmed to be within macrophages using CD68 stain. Some of the bodies displayed a target-like layered appearance. The bodies stained positively with the periodic acid-Schiff, von Kossa, and Perl’s stains, confirming the typical appearance of MG bodies. Numerous hemosiderin-positive granules were seen singly and in clumps within macrophages and other sinusoidal cells. These clumps possibly represent nucleation sites for the development of MG bodies. GMS and PAS stains were negative for fungal elements. Case 2 At autopsy, both adrenal glands had focal chronic inflammation with prominent plasma cells and a small abscess in one gland. This inflammation was similar to that found in the orbital syphilitic lesion found on biopsy. Although this raises the possibility of
Fig. 1. (A–D) Case 1. (A) There are numerous Michaelis-Gutmann (MG) bodies with different stages of development, mostly located in macrophages (H&E, bar = 25 m). (B) MG bodies are calcified (arrows) (Von Kossa, bar = 25 m). (C) MG bodies contain hemosiderin (arrows). Other small iron-positive granules may be nascent MG bodies (Perl’s iron stain, bar = 50 m). (D) Several MG bodies are present within macrophage cytoplasm (CD68-positive) along with other small granules. The large MG bodies are CD68-negative. The small granules are likely nascent MG bodies. They are refractile and CD68-negative in their centers (CD68, bar = 50 m). (E–J) Case 2. (E) There are numerous interstitial and intravascular MG bodies. There is also mild portal mononuclear cell infiltrate (H&E, bar = 50 m). (F) Many MG bodies, as here, have a targetoid appearance (H&E, bar = 12.5 m). (G) This MG body is located within a macrophage (CD68, bar = 25 m). (H) This MG body is extracellular (CD68, bar = 25 m). (I) MG bodies are negative for Herpes simplex stain (Herpes simplex type 1, bar = 25 m). (J) MG bodies are negative for CMV (CMV, bar = 25 m).
Please cite this article in press as: N. Botros, et al., Malakoplakia of liver: Report of two cases, Pathol. – Res. Pract (2014), http://dx.doi.org/10.1016/j.prp.2014.03.004
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Table 1 Reports of malakoplakia apparently confined to liver. Reference
Age/sex
Underlying disease
Diagnostic material
Moldavski and Rustamov [8] De Saint-Maur and Gallot [5] Robertson et al. [10]
34/female 68/female 54/female
Miliary tuberculosis with hepatic pseudocyst Infected polycystic liver; E. coli Liver abscess following immunosuppression for systemic lupus erythematosus; E. coli and Acinetobacter
Autopsy Segmentectomy Wedge biopsy
Boucher et al. [2] Hartman et al. [6] Botros et al. (present report)
43/male 19/male 53/male 60/male
Perforated colonic diverticulum; E. coli and Enterococcus Small bowel ileus following Klebsiella pneumonia Systemic lupus erythematosus treated with steroids; Stenotrophomonas and enterococcus Tertiary syphilis with orbital involvement, adrenal abscess
Segmentectomy Needle core biopsy Autopsy Autopsy
syphilis in the adrenal glands, Treponema organisms were not identified at that site on Steiner stain. The liver at autopsy was grossly normal. Histologically, MG bodies were found in the liver, especially in portal tracts (Fig. 1). MG bodies were not found in adrenal glands, kidneys, spleen, or any other organ sampled. MG bodies were calcified and contained hemosiderin. Viral stains of liver for Herpes I and II and CMV were negative. Discussion Malakoplakia, a Greek term meaning soft (malako) plaque (plakia), is a rare and distinctive chronic inflammatory process. The disease was discovered and named by von Hansemann in 1901 (published in 1903) [15], with further descriptions reported by Michaelis and Gutmann in 1902 [4,7]. It was first reported and is most commonly seen in the urinary bladder. It has since been described to occur elsewhere in the genitourinary tract and also in gastrointestinal tract, lung, skin, bone, conjunctiva, adrenal gland and liver. Primary hepatic malakoplakia has been reported in five cases in the literature (Table 1) [2,5,8,10]. Hepatic involvement secondary to renal malakoplakia has been reported in two additional cases [3,13]. The pathogenesis of malakoplakia has been discussed [16]. The role of bacterial infection is evident, as this was present in almost all reported cases, regardless of the site of organ involvement. The most commonly associated infections are those of Klebsiella or Escherichia coli, although other gram-negative, gram-positive, and acid-fast bacilli have been implicated. An association with some unusual organisms, such as Rhodococcus equi and Paracoccidioides brasiliensis, has been reported [6]. A defective immune system has frequently been associated with malakoplakia. Patients are often immunosuppressed or have an autoimmune disease, neoplasm, organ transplant, or acquired immunodeficiency syndrome. In several patients, macrophages were shown to be able to ingest but not kill specific organisms [14]. Partially digested bacteria accumulate inside the macrophages with subsequent deposition of calcium and iron on residual bacterial glycolipid. Some authors have proposed that low levels of intracellular cyclic guanosine monophosphate may interfere with adequate microtubular function and lysosomal activity, leading to incomplete elimination of bacteria from macrophages [1]. Thus, it is likely that malakoplakia occurs when a host becomes infected with organisms that cannot be controlled because of defective bacterial killing or generalized immunosuppression. However, even with underlying cellular defects, high cure rates have been associated with the use of antibiotics that can penetrate the cell membrane and concentrate in macrophages [16]. Clinical findings in malakoplakia may vary from a silent nodule to various organ-specific manifestations [16]. Lesions can be solitary, multifocal or present as a large mass. The typical lesions in urothelial and colonic mucosa are variably sized, soft, yellowto-brown plaques or polyps with central erosion and peripheral hyperemia [12].
Three phases have been described in the histopathologic evolution of malakoplakia [11]. The early phase consists of macrophages (von Hansemann histiocytes) and plasma cells in an edematous stroma. No MG bodies can be seen at this stage. The granulomatous phase displays many lymphocytes and plump macrophages containing typical calcified MG bodies. The fibrosing or healing phase is characterized by interwoven fibroblasts and strands of thickened collagen admixed with macrophages and sparse MG bodies [6]. Our first patient was an immunosuppressed host and had Stenotrophomonas bacteremia. Some organisms of this genus are prone to biofilm formation [9] and may have caused iron deposition and clumping of the organism in the hepatic macrophages. In the second patient, malakoplakia was possibly related to infection with Treponema organisms. These are the sixth and seventh reported cases in the medical literature of malakoplakia that were documented solely in the liver and the second and third of those to be diagnosed on autopsy. To our knowledge, the association with Stenotrophomonas maltophilia (in case 1) and Treponema pallidum (in case 2) was not reported previously. Both cases possibly represent late granulomatous and early fibrous phase of malakoplakia. As shown in the two cases (Fig. 1), MG bodies may occur in small numbers with mild or no accompanying inflammatory infiltrate. Some can be extracellular. These are likely residual calcific deposits after resolution of the active phase. MG bodies can be visualized by PAS stain, von Kossa stain for calcium, and Prussian blue stain for iron. Mortality in patients with malakoplakia is related to the underlying immunosuppression or preexisting condition rather than to the lesion itself [2]. In both of our cases, malakoplakia was discovered incidentally on autopsy. However, a diagnosis of hepatic malakoplakia provides a clue as to the presence of a chronic systemic infection and/or a defect of the innate immune system with macrophage dysfunction.
References [1] N.I. Abdou, C. NaPombejara, A. Sagawa, C. Ragland, D.J. Stechschulte, U. Nilsson, et al., Malakoplakia: evidence for monocyte lysosomal abnormality correctable by cholinergic agonist in vitro and in vivo, N. Engl. J. Med. 297 (1977) 1413–1419. [2] L. Boucher, A. Makoto, E. Lee, M. Cibull, Malakoplakia of liver associated with perforated colonic diverticulum: a case report and review of the literature, J. Clin. Gastroenterol. 19 (1994) 318–320. [3] C.S. Chen, M.K. Lai, S. Hsueh, T.L. Hwang, C.K. Chuang, Renal malacoplakia with secondary hepato-duodenal involvement, J. Urol. 151 (1994) 982–985. [4] I. Damjanov, S.M. Katz, Malakoplakia, Pathobiol. Annu. 16 (Pt 2) (1981) 103–126 (Review). [5] P. De Saint-Maur, D. Gallot, Malakoplakie hepatique compliquant une polykystose, Ann. Pathol. 10 (1990) 50–51 (Letter). [6] G. Hartman, S.L. Young, G. Chejfec, Malakoplakia of liver diagnosed by needle core biopsy, Arch. Pathol. Lab. Med. 126 (2002) 372–374. [7] L. Michaelis, C. Gutmann, Über Einschlüsse in Blasentumoren, Z. Klin. Med. 47 (1902) 208–215. [8] M. Moldavski, I. Rustamov, Multichamber pseudocyst of the liver with malakoplakia, Klin. Khir. 9 (1984) 64–65 (in Russian). [9] A. Pompilio, V. Crocetta, P. Confalone, M. Nicoletti, A. Petrucca, S. Guarnieri, E. Fiscarelli, V. Savini, R. Piccolomini, G. Di Bonaventura, Adhesion to and biofilm formation on IB3-1 bronchial cells by Stenotrophomonas maltophilia isolates from cystic fibrosis patients, BMC Microbiol. 10 (2010) 102.
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[10] S. Robertson, R. Higgins, C. Powell, Malakoplakia of liver: a case report, Hum. Pathol. 22 (1991) 1294–1295. [11] B. Smith, Malakoplakia of the urinary tract: a study of twenty-four cases, Am. J. Clin. Pathol. 43 (1965) 409–417. [12] M.J. Stanton, W. Maxted, Malacoplakia: a study of the literature and current concepts of pathogenesis, diagnosis and treatment, J. Urol. 125 (1981) 139–146. [13] D.E. Sung, E. Yu, C.S. Kim, J.-Y. Ro, Renal malakoplakia with secondary hepatic extension: a case report, Korean J. Parasitol. 37 (2003) 199–203 (in Korean).
[14] R. van Crevel, J. Curfs, A.J. van der Ven, K. Assmann, J.F. Meis, J.W. van der Meer, Functional and morphological monocyte abnormalities in a patient with malakoplakia, Am. J. Med. 105 (1998) 74–77. [15] D. Von Hansemann, Über Malakoplakie der Harnblase, Virchows Arch. (Pathol. Anat.) 173 (1903) 302–308. [16] G. Yousef, B. Naghibi, Malakoplakia outside the urinary tract, Arch. Pathol. Lab. Med. 131 (2007) 297–300.
Please cite this article in press as: N. Botros, et al., Malakoplakia of liver: Report of two cases, Pathol. – Res. Pract (2014), http://dx.doi.org/10.1016/j.prp.2014.03.004
ARTICLE IN PRESS Pathology – Research and Practice xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Pathology – Research and Practice journal homepage: www.elsevier.com/locate/prp
Teaching cases
Malakoplakia of liver: Report of two cases Noha Botros a,∗ , Sen R. Yan b , Ian R. Wanless a a b
Department of Pathology, Dalhousie University, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia B3H 1V8, Canada Department of Pathology, Dr. Chalmers Regional Hospital, Fredericton, NB, Canada
a r t i c l e
i n f o
Article history: Received 25 April 2013 Received in revised form 5 December 2013 Accepted 12 March 2014 Keywords: Malakoplakia Liver Michaelis-Gutmann bodies
a b s t r a c t Malakoplakia is an unusual chronic inflammatory condition characterized by the presence of MichaelisGutmann bodies. Patients with malakoplakia often have an immunodeficiency state. It is believed that malakoplakia results from a defective macrophage response to phagocytosed bacteria. Malakoplakia most commonly affects the genitourinary tract. Cases confined to the liver are rare, with only five cases described in the literature. We report two cases of malakoplakia of liver; both were incidental autopsy findings. The first case involves a 53-year-old man with systemic lupus erythematosus and chronic refractory pancytopenia who presented with febrile neutropenia. His blood culture was positive for Stenotrophomonas maltophilia and Enterococcus faecium, and he subsequently developed invasive pulmonary aspergillosis. The second case involves a 60-year-old man who presented with a mass in periorbital tissue which, on biopsy, showed inflammation and Treponema-like spirochetes. He died unexpectedly at home. Autopsy revealed adrenal gland chronic inflammation and abscess. Both cases had grossly normal livers with microscopic findings of calcified targetoid structures consistent with Michaelis-Gutmann bodies. In these cases, malakoplakia was an incidental finding confined to liver. Although asymptomatic in these cases, diagnosis in the liver may be useful to initiate a search for hepatic or non-hepatic infections. © 2014 Elsevier GmbH. All rights reserved.
Introduction Malakoplakia is a distinctive inflammatory condition characterized by the presence of histiocytic cells with eosinophilic granular cytoplasm, often known as “von Hansemann’s histiocytes”, accompanied by the pathognomonic intracellular and extracellular siderocalcific Michaelis-Gutmann (MG) bodies [2]. The urinary bladder is the most common site of involvement. Malakoplakia of the liver is rare, with only five cases documented in the world literature [2,5,6,8,10]. We report two cases of liver malakoplakia. Both were incidental autopsy findings. Case reports Case 1 A 53-year-old man with chronic seizure disorder developed refractory pancytopenia associated with a monoclonal gammopathy. One year later, he had a complicated course with pneumonia
∗ Corresponding author. Tel.: +1 902 412 2683. E-mail address: [email protected] (N. Botros).
and probable viral encephalitis which was followed 3 months later with bilateral deep vein thrombosis and pulmonary embolism. Laboratory findings established a diagnosis of systemic lupus erythematosus, and he was started on steroids. Six months later, a renal biopsy was performed that showed membranous nephritis typical of lupus nephritis. He presented one week after the biopsy with rigors and urinary urgency. On admission, he was found to have severe febrile neutropenia. In the hospital, he had multiple recurrent febrile episodes, and blood culture was positive for Stenotrophomonas maltophilia and Enterococcus faecium. A bone marrow biopsy showed severe trilineage hypocellularity and abnormal lymphocytic infiltrate. Despite multiple courses of broad spectrum antibiotics and repeated blood transfusions, he developed progressive respiratory deterioration with bilateral pulmonary consolidation. He died of respiratory failure two weeks later. An autopsy was performed.
Case 2 A 60-year-old man presented with an acute vision problem. A CT scan showed a destructive bony process involving the lateral wall of the left orbit and sphenoid bone, which was clinically suspicious for malignancy. Biopsy of the lesion showed destructive inflammatory
http://dx.doi.org/10.1016/j.prp.2014.03.004 0344-0338/© 2014 Elsevier GmbH. All rights reserved.
Please cite this article in press as: N. Botros, et al., Malakoplakia of liver: Report of two cases, Pathol. – Res. Pract (2014), http://dx.doi.org/10.1016/j.prp.2014.03.004
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process involving bone, skeletal muscle and lacrimal gland. Plasma cells, macrophages and numerous neutrophilic microabscesses were seen. Scattered Treponema-like spirochetes were identified on Steiner stain. The biopsy findings were highly suggestive of a gummatous lesion of syphilis. He died unexpectedly at home, and an autopsy was done. Pathologic findings Case 1 Autopsy showed invasive pulmonary aspergillosis with extensive fungal colonization of both lungs. Features included diffuse alveolar damage, fungal invasion of vessel walls, thrombosis, and infarcts. The liver was grossly normal with incidental microscopic findings of mild portal lymphoid and macrophage infiltration without significant fibrosis (Fig. 1). There were multiple, small round to oval,
calcified bodies (calcospherites) located within portal interstitium and sinusoids. The bodies were either intracellular or extracellular. Many of the bodies were confirmed to be within macrophages using CD68 stain. Some of the bodies displayed a target-like layered appearance. The bodies stained positively with the periodic acid-Schiff, von Kossa, and Perl’s stains, confirming the typical appearance of MG bodies. Numerous hemosiderin-positive granules were seen singly and in clumps within macrophages and other sinusoidal cells. These clumps possibly represent nucleation sites for the development of MG bodies. GMS and PAS stains were negative for fungal elements. Case 2 At autopsy, both adrenal glands had focal chronic inflammation with prominent plasma cells and a small abscess in one gland. This inflammation was similar to that found in the orbital syphilitic lesion found on biopsy. Although this raises the possibility of
Fig. 1. (A–D) Case 1. (A) There are numerous Michaelis-Gutmann (MG) bodies with different stages of development, mostly located in macrophages (H&E, bar = 25 m). (B) MG bodies are calcified (arrows) (Von Kossa, bar = 25 m). (C) MG bodies contain hemosiderin (arrows). Other small iron-positive granules may be nascent MG bodies (Perl’s iron stain, bar = 50 m). (D) Several MG bodies are present within macrophage cytoplasm (CD68-positive) along with other small granules. The large MG bodies are CD68-negative. The small granules are likely nascent MG bodies. They are refractile and CD68-negative in their centers (CD68, bar = 50 m). (E–J) Case 2. (E) There are numerous interstitial and intravascular MG bodies. There is also mild portal mononuclear cell infiltrate (H&E, bar = 50 m). (F) Many MG bodies, as here, have a targetoid appearance (H&E, bar = 12.5 m). (G) This MG body is located within a macrophage (CD68, bar = 25 m). (H) This MG body is extracellular (CD68, bar = 25 m). (I) MG bodies are negative for Herpes simplex stain (Herpes simplex type 1, bar = 25 m). (J) MG bodies are negative for CMV (CMV, bar = 25 m).
Please cite this article in press as: N. Botros, et al., Malakoplakia of liver: Report of two cases, Pathol. – Res. Pract (2014), http://dx.doi.org/10.1016/j.prp.2014.03.004
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Table 1 Reports of malakoplakia apparently confined to liver. Reference
Age/sex
Underlying disease
Diagnostic material
Moldavski and Rustamov [8] De Saint-Maur and Gallot [5] Robertson et al. [10]
34/female 68/female 54/female
Miliary tuberculosis with hepatic pseudocyst Infected polycystic liver; E. coli Liver abscess following immunosuppression for systemic lupus erythematosus; E. coli and Acinetobacter
Autopsy Segmentectomy Wedge biopsy
Boucher et al. [2] Hartman et al. [6] Botros et al. (present report)
43/male 19/male 53/male 60/male
Perforated colonic diverticulum; E. coli and Enterococcus Small bowel ileus following Klebsiella pneumonia Systemic lupus erythematosus treated with steroids; Stenotrophomonas and enterococcus Tertiary syphilis with orbital involvement, adrenal abscess
Segmentectomy Needle core biopsy Autopsy Autopsy
syphilis in the adrenal glands, Treponema organisms were not identified at that site on Steiner stain. The liver at autopsy was grossly normal. Histologically, MG bodies were found in the liver, especially in portal tracts (Fig. 1). MG bodies were not found in adrenal glands, kidneys, spleen, or any other organ sampled. MG bodies were calcified and contained hemosiderin. Viral stains of liver for Herpes I and II and CMV were negative. Discussion Malakoplakia, a Greek term meaning soft (malako) plaque (plakia), is a rare and distinctive chronic inflammatory process. The disease was discovered and named by von Hansemann in 1901 (published in 1903) [15], with further descriptions reported by Michaelis and Gutmann in 1902 [4,7]. It was first reported and is most commonly seen in the urinary bladder. It has since been described to occur elsewhere in the genitourinary tract and also in gastrointestinal tract, lung, skin, bone, conjunctiva, adrenal gland and liver. Primary hepatic malakoplakia has been reported in five cases in the literature (Table 1) [2,5,8,10]. Hepatic involvement secondary to renal malakoplakia has been reported in two additional cases [3,13]. The pathogenesis of malakoplakia has been discussed [16]. The role of bacterial infection is evident, as this was present in almost all reported cases, regardless of the site of organ involvement. The most commonly associated infections are those of Klebsiella or Escherichia coli, although other gram-negative, gram-positive, and acid-fast bacilli have been implicated. An association with some unusual organisms, such as Rhodococcus equi and Paracoccidioides brasiliensis, has been reported [6]. A defective immune system has frequently been associated with malakoplakia. Patients are often immunosuppressed or have an autoimmune disease, neoplasm, organ transplant, or acquired immunodeficiency syndrome. In several patients, macrophages were shown to be able to ingest but not kill specific organisms [14]. Partially digested bacteria accumulate inside the macrophages with subsequent deposition of calcium and iron on residual bacterial glycolipid. Some authors have proposed that low levels of intracellular cyclic guanosine monophosphate may interfere with adequate microtubular function and lysosomal activity, leading to incomplete elimination of bacteria from macrophages [1]. Thus, it is likely that malakoplakia occurs when a host becomes infected with organisms that cannot be controlled because of defective bacterial killing or generalized immunosuppression. However, even with underlying cellular defects, high cure rates have been associated with the use of antibiotics that can penetrate the cell membrane and concentrate in macrophages [16]. Clinical findings in malakoplakia may vary from a silent nodule to various organ-specific manifestations [16]. Lesions can be solitary, multifocal or present as a large mass. The typical lesions in urothelial and colonic mucosa are variably sized, soft, yellowto-brown plaques or polyps with central erosion and peripheral hyperemia [12].
Three phases have been described in the histopathologic evolution of malakoplakia [11]. The early phase consists of macrophages (von Hansemann histiocytes) and plasma cells in an edematous stroma. No MG bodies can be seen at this stage. The granulomatous phase displays many lymphocytes and plump macrophages containing typical calcified MG bodies. The fibrosing or healing phase is characterized by interwoven fibroblasts and strands of thickened collagen admixed with macrophages and sparse MG bodies [6]. Our first patient was an immunosuppressed host and had Stenotrophomonas bacteremia. Some organisms of this genus are prone to biofilm formation [9] and may have caused iron deposition and clumping of the organism in the hepatic macrophages. In the second patient, malakoplakia was possibly related to infection with Treponema organisms. These are the sixth and seventh reported cases in the medical literature of malakoplakia that were documented solely in the liver and the second and third of those to be diagnosed on autopsy. To our knowledge, the association with Stenotrophomonas maltophilia (in case 1) and Treponema pallidum (in case 2) was not reported previously. Both cases possibly represent late granulomatous and early fibrous phase of malakoplakia. As shown in the two cases (Fig. 1), MG bodies may occur in small numbers with mild or no accompanying inflammatory infiltrate. Some can be extracellular. These are likely residual calcific deposits after resolution of the active phase. MG bodies can be visualized by PAS stain, von Kossa stain for calcium, and Prussian blue stain for iron. Mortality in patients with malakoplakia is related to the underlying immunosuppression or preexisting condition rather than to the lesion itself [2]. In both of our cases, malakoplakia was discovered incidentally on autopsy. However, a diagnosis of hepatic malakoplakia provides a clue as to the presence of a chronic systemic infection and/or a defect of the innate immune system with macrophage dysfunction.
References [1] N.I. Abdou, C. NaPombejara, A. Sagawa, C. Ragland, D.J. Stechschulte, U. Nilsson, et al., Malakoplakia: evidence for monocyte lysosomal abnormality correctable by cholinergic agonist in vitro and in vivo, N. Engl. J. Med. 297 (1977) 1413–1419. [2] L. Boucher, A. Makoto, E. Lee, M. Cibull, Malakoplakia of liver associated with perforated colonic diverticulum: a case report and review of the literature, J. Clin. Gastroenterol. 19 (1994) 318–320. [3] C.S. Chen, M.K. Lai, S. Hsueh, T.L. Hwang, C.K. Chuang, Renal malacoplakia with secondary hepato-duodenal involvement, J. Urol. 151 (1994) 982–985. [4] I. Damjanov, S.M. Katz, Malakoplakia, Pathobiol. Annu. 16 (Pt 2) (1981) 103–126 (Review). [5] P. De Saint-Maur, D. Gallot, Malakoplakie hepatique compliquant une polykystose, Ann. Pathol. 10 (1990) 50–51 (Letter). [6] G. Hartman, S.L. Young, G. Chejfec, Malakoplakia of liver diagnosed by needle core biopsy, Arch. Pathol. Lab. Med. 126 (2002) 372–374. [7] L. Michaelis, C. Gutmann, Über Einschlüsse in Blasentumoren, Z. Klin. Med. 47 (1902) 208–215. [8] M. Moldavski, I. Rustamov, Multichamber pseudocyst of the liver with malakoplakia, Klin. Khir. 9 (1984) 64–65 (in Russian). [9] A. Pompilio, V. Crocetta, P. Confalone, M. Nicoletti, A. Petrucca, S. Guarnieri, E. Fiscarelli, V. Savini, R. Piccolomini, G. Di Bonaventura, Adhesion to and biofilm formation on IB3-1 bronchial cells by Stenotrophomonas maltophilia isolates from cystic fibrosis patients, BMC Microbiol. 10 (2010) 102.
Please cite this article in press as: N. Botros, et al., Malakoplakia of liver: Report of two cases, Pathol. – Res. Pract (2014), http://dx.doi.org/10.1016/j.prp.2014.03.004
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Please cite this article in press as: N. Botros, et al., Malakoplakia of liver: Report of two cases, Pathol. – Res. Pract (2014), http://dx.doi.org/10.1016/j.prp.2014.03.004
