A 54-year-old man presented with a several-week history of fever, diarrhea, and jaundice. His past medical history was significant for a liver transplant 1 year earlier for hepatocellular carcinoma secondary to hepatitis C cirrhosis, and a second liver transplant performed 10 months later, after failure of the first liver transplant. Maintenance immunosuppression included prednisone and sirolimus. Laboratory findings included the following values: alanine aminotransferase, 353 U/L (normal, <48 U/L); aspartate aminotransferase, 482 U/L (normal, <48 U/L); and total bilirubin, 24.0 mg/dL (normal, <1.3 mg/ dL). A liver biopsy showed fibrosing cholestatic hepatitis. A pelvic computed tomographic scan revealed diffuse wall thickening of the sigmoid colon. Pale, edematous-appearing colonic mucosa was visualized during a flexible sigmoidoscopy, and multiple random colon biopsies were taken. Microscopic examination of the sigmoid colon biopsies revealed expansion of the lamina propria by aggregates of large histiocytes containing round inclusions of varying sizes in their cytoplasm (Figure 1). Many of these inclusions had a targetoid appearance with a basophilic rim and central round basophilic body in a clear interior (Figure 2), which stained positively for periodic acid–Schiff (Figure 3), calcium (Figure 4), and iron stain.

What is your diagnosis?

Malakoplakia, derived from the Greek malakos (soft) and plakos (plaque) is a rare inflammatory disease that was first described by Michaelis and Gutmann in 1902.1 Although malakoplakia usually involves the urinary tract, it has been reported in many other sites, including the gastrointestinal tract, pancreas, liver, lymph nodes, skin, respiratory tract, adrenal gland, vagina, and brain. Involvement of the gastrointestinal tract ranks second in frequency; most cases involve the rectum and colon.2 

Malakoplakia involving the colon has a distinctive gross and microscopic appearance. Colonic involvement is segmental or diffuse, and early lesions often appear soft, flat, and yellow-tan. Later, lesions become raised, tan-gray, with peripheral hyperemia and a central depressed area. Although submucosal lesions secondarily elevate the mucosa into soft yellow-tan plaques, often the overlying mucosa appears intact.3 

Histologically, malakoplakia is characterized by aggregates of granular histiocytes, known as von Hansemann cells, with intracellular and extracellular Michaelis-Gutmann bodies intermingled with lymphocytes and plasma cells. Michaelis-Gutmann bodies are phagolysomes that have become encrusted with calcium and iron salts and are diagnostic of malakoplakia. They vary in size from 2 to 10 μm, have a targetoid appearance due to concentric laminations, and stain with periodic acid–Schiff, Prussian blue, and von Kossa calcium stain.3 

Malakoplakia is clearly related to chronic bacterial infections, mostly by Escherichia coli.4 The etiology is most likely an abnormal macrophagic response resulting in incompletely digested bacterial fragments and subsequent mineralization. Malakoplakia is often associated with a concomitant generalized disease capable of altering the immune system and occurs with increased frequency in immunosuppressed transplant recipients.4,5 Approximately 40% of malakoplakia cases involving anatomic sites other than the urinary tract have been associated with immunosuppression.6 Although many cases of malakoplakia arising in renal transplant recipients have been described, our review of the literature revealed only 1 previously reported case following liver transplantation.7 Along with antibiotic therapy and cholinergic agonists, which promote phagocytic activity, a dramatic reduction of immunosuppressive medication is often a necessary component of medical treatment of malakoplakia in this setting.8,9 

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The authors have no relevant financial interest in the products or companies described in this article.

Author notes

Corresponding author: David M. Weinrach, MD, Department of Surgical Pathology, Feinberg School of Medicine, Northwestern University, Northwestern Memorial Hospital, Feinberg 7-325, 251 E Huron St, Chicago, IL 60611 (Dweinrach@md.northwestern.edu)