A Case of Urinary Bladder Malakoplakia in a Young French Bulldog: Diagnostic and Therapeutic Issues.

A 3-month-old female French Bulldog presented with hematuria, severe pollakiuria, and urinary incontinence lasting for 1.5 months. Broad-spectrum empirical antibiotic therapy and nonsteroidal anti-inflammatory drugs were initiated by the referring veterinarian. Due to a lack of improvement, the dog was referred. At referral examination, urinary clinical signs persisted (hematuria, severe pollakiuria) and a firm bladder was noted. Abdominal ultrasonography revealed severe, diffuse bladder wall thickening with a significant reduction in the bladder lumen. Urinary tract endoscopy showed whitish exophytic proliferations throughout the entire bladder wall. Histological bladder wall analysis led to a diagnosis of bladder malakoplakia. Prolonged antibiotic therapy with fluoroquinolones was prescribed and resulted in clinical remission despite persistent bacteria in the bladder wall. This report describes a case of successfully medically managed bladder malakoplakia, a very rare condition in veterinary medicine, well documented in humans.

A case of canine intestinal malakoplakia.

Malakoplakia is a rare chronic granulomatous disease usually affecting the urinary bladder and other locations. In humans, the gastrointestinal tract is the second most common location but there are no reports of intestinal malakoplakia in animals. A 10-month-old female French Bulldog was presented with chronic haemorrhagic diarrhoea and anorexia with normochromic-normocytic anaemia and hypoalbuminaemia. Grossly, there was mucosal thickening and ulceration of the caecum, colon and rectum. Microscopically, transmural sheets of foamy macrophages were seen in these tissues. Macrophages were periodic acid-Schiff, vimentin and ionized calcium-binding adaptor molecule 1 positive and contained von Kossa- and Prussian blue-positive Michaelis-Gutmann bodies. Giemsa staining revealed rod-shaped bacterial colonies and fluorescence in-situ hybridization demonstrated Escherichia coli within macrophages. This is the first reported case of intestinal malakoplakia in domestic animals. Pathological features of intestinal malakoplakia share many similarities with ulcerative histiocytic colitis in dogs but it is unclear if they are different forms of the same pathological process or distinct entities.

Malakoplakia of the urinary bladder in a young French Bulldog.

CASE DESCRIPTION: A 4-month-old 5.9-kg sexually intact female French Bulldog was presented because of recurrent urinary tract infections in combination with pollakiuria, hematuria, and urinary incontinence. CLINICAL FINDINGS: A diagnosis of malakoplakia was made on the basis of results of hematologic and serum biochemical testing, abdominal ultrasonography, bacterial culture, and cystoscopic biopsies of the urinary bladder wall. Biopsy samples were sent for routine histologic examination and fluorescence in situ hybridization to confirm the presence of intracellular and subendothelial bacteria. TREATMENT AND OUTCOME: Treatment with enrofloxacin was started after the diagnosis of malakoplakia was confirmed. During treatment, polypoid changes in the urinary bladder decreased dramatically but did not disappear. On follow-up ultrasonography after 12 weeks of treatment, marked improvement was visible and results of repeated bacterial culture and fluorescence in situ hybridization of bladder wall samples were negative. The patient was free from clinical signs and had an ultrasonographically normal urinary bladder 59 weeks after antimicrobial treatment was discontinued. CLINICAL RELEVANCE: Malakoplakia, a granulomatous disease characterized by impaired histiocytes that are unable to completely digest phagocytized bacteria, is a very rare disease in dogs, but early suspicion of the condition is essential to allow timely diagnosis and avoid disease progression and the need for prolonged treatment. Malakoplakia should be considered in young dogs with chronic urinary tract infections; the diagnosis can be made through a combination of histologic examination and fluorescence in situ hybridization of bladder wall biopsy samples.

Malakoplakia in the Urinary Bladder of 4 Puppies.

Malakoplakia in humans most often affects the urinary bladder and is characterized by inflammation with von Hansemann-type macrophages, with or without Michaelis-Gutmann bodies, and is frequently associated with Escherichia coli infection. We describe the microscopic features of malakoplakia in the urinary bladder of 4 puppies. In all cases, the lamina propria of the urinary bladder was markedly expanded by sheets of large, round to polygonal macrophages with intracytoplasmic, periodic acid-Schiff-positive granules and granular inclusions, and rare Prussian blue-positive inclusions. Macrophages were positive for CD18 and Iba1. In 2 cases, Michaelis-Gutmann bodies were detected with hematoxylin and eosin stain and were best demonstrated with von Kossa stain. E. coli infection was confirmed in 2 cases with bacterial culture or polymerase chain reaction (PCR) and sequencing of the bacterial 16S ribosomal RNA gene. Transmission electron microscopy of one case demonstrated macrophages with abundant lysosomes, phagolysosomes, and rod-shaped bacteria. Microscopic features were similar to human cases of malakoplakia. In dogs, the light microscopic characteristics of malakoplakia closely resemble granular cell tumors and histiocytic ulcerative colitis.

Malakoplakia of the Bladder in a 4-Month-Old Puppy.

A 4 mo old female Staffordshire bull terrier puppy was presented with chronic Escherichia coli cystitis. Ultrasound and cystoscopic examination revealed innumerable, intraluminal, finger-like proliferations arising from the dorsal urinary bladder (UB) wall. Histological examination of mucosal biopsies obtained by cystoscopy was suggestive of granulomatous cystitis. The proliferative lesions were removed surgically and submitted for histological examination. The UB submucosa was heavily infiltrated by macrophages with periodic acid-Schiff-positive cytoplasm exhibiting rare Michaelis-Gutmann bodies, leading to the diagnosis of malakoplakia. The puppy was prescribed with sulfamethoxazole-trimethoprim. The urinary signs disappeared despite the persistent UB wall thickening revealed by abdominal ultrasound. Urine culture performed during the ninth week of treatment showed a persistent infection by E coli resistant to sulfamethoxazole-trimethoprim. The dog was switched to doxycycline but was then lost to follow-up. Malakoplakia is a chronic granulomatous inflammation well documented in humans. Its pathophysiology is not fully understood, but bacterial infection, immunodepression, and a defective lysosomal function may lead to the intracytoplasmic accumulation of partially degraded bacteria that can subsequently mineralize to form the Michaelis-Gutmann bodies. Malakoplakia should be suspected when UB mass lesions are identified in a young dog with bacterial cystitis.

Malakoplakia with digestive tract involvement in a pig.

Malakoplakia is a rare, granulomatous, inflammatory disease that mimics malignant tumors and can affect any organ. Herein is described a case of malakoplakia in a 10-month-old slaughter pig. Diffuse, pleomorphic, round cell infiltrates, mainly histiocytes, with a tumor-like growth pattern at gross examination, infiltrated the stomach, pancreas, omentum, and mesenteric lymph nodes. The histiocytes and multinucleated giant cells had concentric, target-like inclusions known as Michaelis-Gutmann bodies. Microorganisms were not detected by the periodic acid-Schiff reaction, Ziehl-Neelsen, Gram, and Warthin-Starry staining or by electron microscopic and bacteriologic investigations. Porcine circovirus type 2 and porcine reproductive and respiratory syndrome viruses were not detected by immunohistochemistry in the sections examined.

Successful treatment of malakoplakia of the bladder in a kitten.

A 4-month-old female kitten presented with chronic lower urinary tract signs and Escherichia coli cystitis, and was diagnosed with urinary bladder malakoplakia based upon histopathology. The kitten was treated with a prolonged antibiotic course and the malakoplakia resolved. Malakoplakia is a chronic granulomatous reaction characterized by the formation of Michaelis-Gutman bodies within von Hansemann macrophages. It is well described in humans, but has never been documented in a living veterinary patient. This case report describes the first successful treatment of malakoplakia in veterinary medicine.

Malakoplakia in the urinary bladder of a kitten.

Malakoplakia is a form of chronic granulomatous inflammation that in humans most commonly affects the urinary bladder of middle-aged women. Naturally occurring malakoplakia is rare in animals, having been described twice in the pig only. An 8-week-old kitten was diagnosed with malakoplakia of the urinary bladder after a 3-week history of dysuria. Post-mortem examination revealed a markedly enlarged bladder with a diffusely nodular mucosal surface. Microscopically, there was diffuse submucosal infiltration by histiocytes stained positively by periodic acid Schiff (PAS) and described in the human condition as "von Hansemann cells". Intracellular and extracellular "Michaelis-Gutman" inclusion bodies were seen on light and electron microscopical examination. These structures are considered pathognomonic for malakoplakia. The pathogenesis of malakoplakia is enigmatic. Defective function of phagolysosomes is currently suspected to underlie the abnormal accumulation of submucosal histiocytes; however the primary functional defect remains unknown.

Systemic malacoplakia in a breeding pig.

An adult breeding pig had multiple disseminated lesions in several organs of the thoracic and abdominal cavities. Histopathologically, the lesions consisted of accumulated histiocytic cells with a few giant cells and a mild infiltration of lymphocytes and plasma cells associated with concentric laminated spherical Michaelis-Gutmann bodies which stained strongly with haematoxylin and varied in diameter. The histological features of the lesions were similar to those of malacoplakia reported in man. The present case seems to be unique because the characteristic lesions were found in many organs including kidneys, liver, spleen, lungs, gall bladder, small intestine and several lymph nodes. The possibility of the haematogenous spread of malacoplakia was suggested by the frequent formation of the lesions in perivascular areas. The present case should be described as "systemic malacoplakia in a breeding pig".