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ACG Case Rep J
ACG Case Rep J
ACGCRJ
AC9
ACG Case Reports Journal
2326-3253
Wolters Kluwer Maryland, MD

ACGCR-24-0496
10.14309/crj.0000000000001486
00018
3
Case Report
Liver
Malakoplakia in a Transplanted Liver
https://orcid.org/0000-0002-5223-1412
Ansari Zaid MD 1
Ahmad Akram MD 1ahmada5@ccf.org

Bejarano Pablo A. MD 2bejarap@ccf.org

Pinna Antonio MD 3pinnaa@ccf.org

Zervos Xaralambos MD 1zervosx@ccf.org

1 Department of Gastroenterology and Hepatology, Cleveland Clinic, Weston, FL
2 Department of Pathology, Cleveland Clinic, Weston, FL
3 Department of Transplant Surgery, Cleveland Clinic, Weston, FL
Correspondence: Zaid Ansari, MD (ansarizaidnexus@gmail.com).
9 2024
11 9 2024
11 9 e0148629 5 2024
27 7 2024
© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

ABSTRACT

Malakoplakia is a rare acquired histiocytic disorder first described in the urinary bladder. There have been 8 cases reported involving the liver, and this is the first reported case of malakoplakia involving an adult transplanted liver. We report a 63-year-old man with a medical history of orthotopic liver transplantation who presented with fever, chills, and abdominal pain. Imaging found confluent microabscesses in the right lobe of the liver that persisted despite prolonged antibiotics. He was taken to the operating room for a segment 6 hepatectomy of the abscess. Histologically, the inflammatory process showed malakoplakia.

KEYWORDS:

Malakoplakia
liver transplant
liver abscess
liver mass
OPEN-ACCESSTRUE
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pmcINTRODUCTION

Malakoplakia is a rare acquired histiocytic disorder that was first described in the urinary bladder by Leonor Michaelis and Carl Gutmann in 1902 in a patient referred to them by von Hansemann.1,2 In Greek, it means “soft plaque”, and it has mostly been found in the genitourinary system. The pathogenesis of malakoplakia is poorly understood, but it is thought to be secondary to an acquired bactericidal defect in macrophages occurring mostly in immunosuppressed patients or in the setting of autoimmune disease. The diagnosis is typically delayed secondary to lesions mimicking other conditions such as indolent infections or malignancy. There have been 8 cases reported that we were able to locate that involve the liver, with only 1 prior case in a pediatric transplanted liver.3–9 This is the first reported case to our knowledge of malakoplakia involving an adult transplanted liver whose diagnosis required a partial hepatectomy.

CASE REPORT

A 63-year-old man with a medical history of alcohol-associated cirrhosis, hepatocellular carcinoma, and orthotopic liver transplantation 6 months prior with an unremarkable postoperative course presented to clinic with skin rash concerning for graft-versus-host disease (GVHD). Immunosuppression was with tacrolimus 3 mg twice daily and mycophenolate mofetil that had been held 2 weeks prior due to leukopenia and cytomegalovirus viremia. A skin biopsy later reported changes suggestive of graft-versus-host disease. Allograft function was normal, and donor T lymphocyte showed moderate evidence of chimerism (average 82.9%). He was admitted for further evaluation with a bone marrow biopsy and given IV methylprednisolone 1 g once a day, followed by a taper on oral prednisone. A change from tacrolimus to cyclosporine was also made due to unexplained peripheral neurologic manifestations with subsequent resolution.

One month later, he presented with fever, chills, and abdominal pain. An abdominal/pelvic computed tomography found a cluster of confluent microabscesses in the right lobe of the liver forming a mass-like process measuring 11 cm (Figures 1 and 2). He did not have any extrahepatic lesions. He was on prednisone 20 mg daily and cyclosporine 150 mg twice daily at this time, which was switched to prednisone 10 mg daily and back to tacrolimus 3 mg twice daily. Tacrolimus dose was decreased to 1.5 mg twice daily later based on trough levels. Magnetic resonance imaging/magentic resonance cholangiopancreatography showed a similar conglomerate area as well as a 3.3-cm area clustered in the right hepatic lobe (Figures 3 and 4). Endoscopic retrograde cholangiopancreatography did not show any contrast extravasation or filling defects in the cholangiogram. Interventional radiology-guided aspiration was performed and sent for cultures that grew extended-spectrum beta-lactamase Escherichia coli. He was given a 12-week course of IV ertapenem 1 g every 24 hours upon discharge based on culture and sensitivity results.

Figure 1. Abdominal/pelvic computed tomography with contrast: coronal view. Yellow arrow pointing towards complex mass/cluster of microabscesses in the liver.

Figure 2. Computed tomography with contrast liver protocol: axial view. Yellow arrow pointing towards complex mass/cluster of microabscesses in the liver.

Figure 3. Abdominal magnetic resonance imaging without contrast: coronal view. Yellow arrow pointing towards complex mass/cluster of microabscesses in the liver.

Figure 4. Abdominal magnetic resonance imaging without contrast: axial view. Yellow arrow pointing towards complex mass/cluster of microabscesses in the liver.

The patient was admitted to the hospital 3 months later due to worsening abdominal pain and the persistence of the complex mass/microabscesses despite antibiotics. Interventional radiology-guided drainage was attempted but was unsuccessful, and therefore, he was taken to the operating room for a segment 6 hepatectomy of the abscess (Figure 5). Histologically, the inflammatory process showed extensive necrosis and fibroblastic reaction. No evidence of malignancy or infection with acid-fast bacilli or fungi was seen. Mucicarmine stain was negative. CD21 was negative too. Macrophages containing the characteristic Michaelis-Gutmann bodies were present (Figures 6–8). The findings were consistent with a diagnosis of malakoplakia. Skin biopsy was also repeated, which did not show features of malakoplakia and was consistent with GVHD.

Figure 5. The 7 cm resected liver shows clustering plaque nodules of tan-white soft material. This is the first gross image of liver malakoplakia ever published. Black arrows indicates tan white plaque/nodules of malakoplakia.

Figure 6. Cytoplasm of histiocytes contains eye-like targetoid inclusions corresponding to Michaelis-Gutmann bodies (hematoxylin and eosin, 200×). Black arrow showing michaelis-gutmann bodies.

Figure 7. The inclusions are highlighted with a Prussian iron stain (100×). Black arrows pointing towards iron stain positive inclusions.

Figure 8. The inclusions are highlighted with a von Kossa stain indicating their calcium content (100×). Black arrow showing a positive von Kossa stain.

In the following 3 months, attempts at augmenting immunosuppression for his GVHD were complicated by recurrent infections leading to progressive clinical decline and eventual demise.

DISCUSSION

Malakoplakia is characterized by sheets of histiocytes called von Hansemann cells with basophilic inclusions due to intracellular calcium and iron deposition named Michaelis-Gutmann bodies. The pathogenesis is thought to be due to the diminished release of beta-glucuronidase as well as levels of cGMP, which lead to decreased clearance of pathogenic organisms due to the persistence of phagolysosomes.10

The disease occurs in the background of immunocompromise such as HIV, malignancy, or organ transplantation. The most commonly implicated species of bacteria is Escherichia coli, which was also the causative organism in our case. Other organisms have also been reported including Proteus, Klebsiella, Corynebacterium, Pseudomonas, Acinetobacter, Staphylococcus, Streptococcus, Enterococcus, Aerobacter, Rhodococcus, Mycobacterium, Salmonella, and Burkholderia.11

When considering malakoplakia in all organ systems, the mean age at diagnosis is 50 years. The most common site of involvement is the genitourinary system, with the gastrointestinal system being second. The involvement of the genitourinary system typically presents with symptoms such as fever, flank pain, and dysuria. The difficulty lies in distinguishing this condition from chronic infections and tumors. A renal biopsy is usually required. Treatment depends on the extent of the disease and underlying comorbidities. Antibiotics are used for bilateral and multifocal disease, and a resection or nephrectomy may be required for unifocal disease.12 The clinical features are variable depending on the organ system involved—rectal bleeding with gastrointestinal involvement or a skin rash with cutaneous involvement. They can also present as soft yellow to tan lesions or plaques in the affected organ. The evaluation usually requires obtaining a tissue sample to make a diagnosis due to the nonspecific presentation and the clinical differential including malignancy. In our patient, the initial presentation was multiple microabscesses seen on imaging as a complex mass. There were no vascular complications after transplant, and Doppler ultrasound of the hepatic arteries was normal. Graft function was good with normal function tests. Epstein-Barr virus polymerase chain reaction was negative, and there was a low level of cytomegalovirus viremia (<100 IU/mL). Initial aspiration did result in a microbiological diagnosis; however, we did not make a diagnosis until after a hepatectomy and histopathological analysis.

Table 1 summarizes the previously reported cases involving the liver. Two of the 8 cases did not have any signs/symptoms suggesting liver involvement and were diagnosed only after autopsy.6 One case was diagnosed after a liver biopsy for evaluation of cirrhosis, and similar to our case, 4 cases presented as a complex liver mass/abscess.3–5,7,8 Four out of 8 cases did not receive antibiotics as the diagnosis was made after death.5,6,9 One patient had no liver sampling, but malakoplakia was diagnosed on his skin. He had a liver lesion that disappeared after antibiotics; hence, the assumption was made that the liver was involved.7 From the remaining 3 cases, 1 patient died despite prolonged antibiotics and 2 patients had a hepatectomy. Our case is the only reported case that required a hepatectomy for diagnosis and treatment of malakoplakia in a liver transplant.3,4,8

Table 1. Review of prior cases

Reference	Age/sex	Underlying disease/microbiology	Tissue for Diagnosis	Treatment/outcome	
Robertson, 19913	54, F	SLE on immunosuppression/Escherichia coli, Acinetobacter	Wedge biopsy of the liver	Discontinue steroids, unspecified antibiotics	
Boucher, 19944	43, M	Perforated colonic diverticulum/Escherichia coli, Enterococcus, Bacteroides	Hepatectomy	Tobramycin, ampicillin/Unasyn, metronidazole, followed by partial hepatectomy of the right lobe. The patient survived	
Hartman, 20025	19, M	Cirrhosis, small bowel ileus/Klebsiella	Needle core biopsy of the liver	Deceased before Rx	
Botros, 20146	53, M	SLE on immunosuppression/Stenotrophomonas, Enterococcus	Autopsy	Deceased before Rx	
Botros, 20146	60, M	Tertiary syphilis	Autopsy	Deceased before Rx	
Gerard, 20237	16, M	Liver transplant for AIH/Escherichia coli, Rothi, Actinomycetes, Streptococcus	Core biopsy of skin and abdominal wall	Piperacillin/tazobactam, followed by doxycycline and cefdinir. The patient survived	
De Saint-Maur, 19908	34, F	Infected polycystic liver/Escherichia coli	Hepatectomy	Antibiotics not specified	
Moldavski, 19849	68, F	Miliary tuberculosis with hepatic pseudocyst	Autopsy	Deceased before Rx	
AIH, autoimmune hepatitis; SLE, systemic lupus erythematosus; Rx, prescription.

Since the condition is rare, there are no established treatment recommendations. However, the focus of treatment is antibiotics, such as quinolones and trimethoprim/sulfamethoxazole, as well as mitigating the underlying immunosuppression as possible. The duration of therapy depends on the site of involvement as well as the presence or absence of abscess formation.

We were limited in reducing immunosuppression due to his transplant as well as coexistent graft-versus-host disease, which required additional steroids for therapy. We did not use the antibiotics mentioned above as we were able to tailor antibiotic therapy based on culture and sensitivities. We did note a decrease in the size of the complex mass, but medical management was not adequate and source control was required. Interventional radiology-guided aspiration was unable to drain the complex mass, and we opted for surgical evacuation of the abscess with a hepatectomy. After initially weaning off steroids and continuing tacrolimus, chimerism testing was repeated and found to be positive. Skin biopsy was consistent with GVHD, and therefore, he was restarted on prednisone.

Despite not having any further involvement of the liver or malakoplakia found at other sites, our patient had a worsening clinical course due to recurrent infections and GVHD complications. This further highlights the high mortality seen in patients with malakoplakia, as seen in previously documented cases.

As the number of liver transplanted patients increases, it is important to consider malakoplakia as a differential for a complex mass or lesion in patients with suboptimal response to antibiotics. Since histopathology is required for diagnosis, we suggest considering a liver biopsy for recurrent or refractory abscesses with unusual mass-like appearance. Treatment may involve prolonged antibiotics with reduction in immunosuppression if possible, in addition to percutaneous or open surgical procedures.

DISCLOSURES

Author contributions: Z. Ansari, A. Ahmad wrote the manuscript and obtained images; PA Bejarano provided pathology images and reviewed the manuscript; A. Pinna, X. Zervos reviewed and edited the final version of the manuscript. Z. Ansari is the article guarantor.

Financial disclosure: None to report.

Informed consent was obtained for this case report.
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