Malakoplakia: A rare cause of hematochezia in pediatric patients

Abstract

Malakoplakia is a rare inflammatory condition characterized by impaired macrophages unable to completely digest and kill phagocytized bacteria, resulting in partially digested bacterial components accumulating within the phagolysosome. Malakoplakia typically presents in immunocompromised individuals due to underlying disease or to medication effects and is rarely diagnosed in the pediatric population. The urinary tract is the most commonly involved site, followed by the gastrointestinal (GI) tract, mainly affecting the descending colon, sigmoid colon, and rectum. Treatment focuses on the use of antibiotics that concentrate in macrophages such as quinolones and trimethoprim‐sulfamethoxazole as well as cholinergic agents such as bethanechol, which raise intracellular levels of cyclic guanosine monophosphate in macrophages to improve bactericidal activity. We report a rare case of GI tract malakoplakia in a pediatric patient undergoing treatment for leukemia.

1. INTRODUCTION

Malakoplakia is a rare inflammatory condition characterized by impaired macrophages unable to digest and kill phagocytized bacteria, resulting in partially digested bacterial components accumulating within the phagolysosome. ¹ Malakoplakia typically presents in immunocompromised individuals due to underlying disease or medication effects and is rarely diagnosed in the pediatric population. The urinary tract is the most commonly involved site, followed by the gastrointestinal (GI) tract, mainly affecting the descending colon, sigmoid colon, and rectum. ² , ³ Treatment focuses on antibiotics that concentrate in macrophages such as quinolones and trimethoprim‐sulfamethoxazole as well as cholinergic agents such as bethanechol, which raise intracellular levels of cyclic guanosine monophosphate in macrophages to improve bactericidal activity. ⁴ We report a rare case of GI tract malakoplakia in a pediatric patient undergoing treatment for leukemia.

2. CASE REPORT

A 13‐year‐old male being treated for T‐cell lymphoblastic leukemia was referred for gastroenterology consultation for hematochezia. He reported 3 months of bloody stool, passing two to three bowel movements daily described as Bristol type 5–6 with mixed blood and blood with wiping. Polyethylene glycol 3350 was trialed before referral resulting in loose stools without improvement in hematochezia. He had not experienced weight loss, poor appetite, abdominal pain, rashes, arthritis, oral sores, or perianal sores. At consultation, he was in remission on maintenance therapy with daily 6‐mercaptopurine, weekly oral methotrexate, and monthly vincristine and dexamethasone. He was clinically well but was intermittently neutropenic and consistently lymphopenic from chemotherapy.

Physical examination was notable for a benign abdomen and a small nonbleeding external hemorrhoid. Stool culture and polymerase chain reaction testing for Clostridioides difficile, cytomegalovirus, and adenovirus were negative. Colonoscopy revealed multiple semisessile, nonbleeding polyps in the rectum and sigmoid colon ranging from 1 to 5 mm in size (Figures 1 and 2). Polyps were incompletely removed with hot snare and were partially retrieved. The remainder of the colon appeared grossly normal. Histopathology of the polyps showed eroded surface mucosa with entrapped reactive hyperplastic glands and marked expansion of the lamina propria by a dense mixed inflammatory infiltrate. The inflammation had a predominance of pale histiocytes with vacuolated cytoplasm mixed with numerous eosinophils and smaller numbers of neutrophils and lymphocytes. The histiocytes contained numerous basophilic spherical and targetoid inclusions that were strongly positive for von Kossa (calcium) and periodic acid Schiff stains, consistent with Michaelis–Gutmann (MG) bodies of malakoplakia (Figure 3). Additional fungal stain (Grocott–Gömöri's methenamine silver stain) and acid‐fast stain (Kinyoun) were negative for organisms. The remainder of the colon demonstrated no specific histopathologic changes.

Figure 1.

Several 1–5 mm polyps in the rectum. The surrounding mucosa appears erythematous and eroded without evidence of active bleeding.

Figure 2.

Two polyps in the sigmoid colon measuring 3–5 mm. One area of erosion is noted with otherwise normal‐appearing mucosa.

Figure 3.

Histopathology of colonic polyp, noting Michaelis–Gutmann (MG) bodies identified by red circles. Inset is a von Kassa calcium stain which highlights the MG bodies.

The patient was started on levofloxacin and bethanechol, and hematochezia resolved within 1 month. Soon after starting these therapies, he developed bilateral leg pain impacting mobility. Levofloxacin was discontinued given association with myalgias and skeletal pain while continuing bethanechol monotherapy. Leg pain resolved within 3 days of discontinuation, and ciprofloxacin was started. Repeat flexible sigmoidoscopy 4 months after initial colonoscopy was notable for a localized area of mildly nodular and plaque‐covered mucosa in the sigmoid colon and a patchy area of mildly granular mucosa in the rectum. Histopathology demonstrated focal surface erosion of the sigmoid colon and rectum without MG bodies. Ciprofloxacin and bethanechol were discontinued at this time. Chemotherapy was discontinued 5 months later. He had not had recurrence of hematochezia at 12‐month follow‐up.

3. DISCUSSION

Malakoplakia is a rare inflammatory process first described by Leonor Michaelis and Carl Gutmann in 1902. The term “malakoplakia” stems from the Greek words “malakos” and “plakos,” meaning soft and plaque, respectively. Generally affecting adults, there is a bimodal incidence with a main peak in the fifth decade and a smaller peak in adolescence. ⁵ Malakoplakia typically affects the urinary tract, although involvement of other organ systems including GI tract, liver, central nervous system, and lungs is reported. The GI tract, mainly the left colon, is the second most affected organ system. Patients with malakoplakia are typically immunocompromised due to primary disease state or immunosuppressive therapy for disorders such as solid organ transplantation, malignancy, inflammatory bowel disease, and autoimmune disorders. ¹ Pathogenesis is poorly understood, although three possible mechanisms have been suggested including: (1) unusual response to bacteria such as Escherichia coli (found in more than two‐thirds of cases), Mycobacterium tuberculosis, Proteus mirabilis, and Staphylococcus aureus, (2) altered immune response, or (3) abnormal macrophage response due to defective lysosomal function. ²

The presentation of GI malakoplakia is varied and nonspecific ranging from asymptomatic to diarrhea, abdominal pain, or hematochezia. It can lead to significant complications including colonic strictures, GI hemorrhage, or gastric outlet obstruction. ⁶ Endoscopic findings are variable including grossly normal appearing mucosa, unifocal mucosal nodules and plaques, multifocal mucosal nodules and polyps, or mass‐like lesions. ³ The diagnosis is histologic with tissue demonstrating a mixed inflammatory infiltrate of neutrophils, lymphocytes, and plasma cells with MG bodies, the pathognomonic finding for malakoplakia. MG bodies are intracytoplasmic laminated concretions that represent accumulation of calcified, iron‐containing phagolysosomes thought to be partially degraded bacterial organisms. ⁷ The differential diagnosis for the various gross endoscopic findings with histologic findings of histiocytic proliferation includes Crohn's disease, malignancy, and infection such as atypical mycobacteria, Whipple disease, or tuberculosis, although these diagnoses do not include the finding of MG bodies. ¹

Given the rarity of malakoplakia, clinical trials are lacking, and much of the available literature regarding effective treatment comes in the form of case reports without standardized guidelines. ⁷ Treatment most commonly involves systemic antibiotics that penetrate macrophages and optimize the intracellular killing of phagocytized bacteria such as quinolones or trimethoprim‐sulfamethoxazole. Cholinergic agents such as bethanechol have been utilized in combination with antibiotics to raise intracellular levels of cyclic guanosine monophosphate in macrophages improving bactericidal activity. ⁷ , ⁸ , ⁹ Surgical resection has also occurred for various reasons. ⁶ , ⁹

Although most cases of malakoplakia occur in immunocompromised individuals, it can occur in immunocompetent patients and may be the initial finding of an underlying immunocompromised state. ¹⁰ There are few reports of malakoplakia in patients with leukemia. Pathologists should include malakoplakia in the differential diagnosis of pediatric patients with histiocyte inflammation in the GI tract regardless of baseline immunologic status.

This case highlights the importance of including malakoplakia in the differential for GI bleeding in immunocompromised pediatric patients, including those undergoing chemotherapy for leukemia. Further studies are needed to better understand this rare entity with the establishment of guidelines for treatment, monitoring, and follow‐up.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.

ETHICS STATEMENT

Informed assent and consent were obtained from the patient and legal guardian, respectively, for publication of the case details.

Porto A, Lebowitz J, Byrd R, Morgan E, Prozialeck JD. Malakoplakia: a rare cause of hematochezia in pediatric patients. JPGN Rep. 2024;5:360‐362. 10.1002/jpr3.12075