a 3-year - old , female , spayed , domestic shorthair cat presented for dysuria and haematuria , unresponsive to antibiotic treatment . a small , fleshy
ultrasound identified a vaginal mass effect with mixed echogenicity measuring in excess of 3 cm .
vaginoscopy confirmed an extensive , fleshy , irregular mass that was characterised histologically as pyogranulomatous vaginitis , with periodic acid 
a 6 week course of enrofloxacin 5 mg / kg q24h resulted in complete resolution of the mass and clinical signs .
malakoplakia is a rare chronic inflammatory condition that has been previously reported in the bladder of two cats .
this is the first reported feline case with vaginal involvement , intracellular e coli and successful treatment with a fluoroquinolone .
malakoplakia is an important , non - neoplastic differential diagnosis when a mass is identified in the urogenital system of a young cat .
malakoplakia is a rare , chronic inflammatory condition that has been described in humans for over 100 years , most commonly involving the urinary bladder of middle - aged women , although other parts of the urinary tract and , rarely , other organs can be involved .
only more recently has this condition has been described as a spontaneous disease in animals , including two kittens , three pigs , and a cynomolgus monkey .
the term was originally created to describe soft , plaque - like lesions seen within the urinary bladder that were thought to be neoplastic .
grossly , human malakoplakia lesions vary from flat plaques to nodules and masses that resemble tumours .
histology reveals the inflammatory nature of the lesions , which are characterised by large numbers of histiocytes ( referred to as von hansemann cells ) containing periodic acid 
the pathogenesis of this disease is unclear , but it is often linked to a bacterial infection such as escherichia coli , with 8090% of people diagnosed with malakoplakia having a persistent coliform urinary tract infection .
immunosuppression or an innate host immune defect also could play a role , with some cases of malakoplakia reported in humans with aids , neoplasia or receiving immunosuppressive therapy for another disease .
descriptions of malakoplakia frequently identify bacteria associated with histiocytes on light or electron microscopy , and the michaelis 
it has been speculated that this disease is a consequence of impaired bacterial killing by macrophages , perhaps associated with ineffective assembly of microtubules .
experimental studies support this theory ; with similar lesions created in the kidney and testes of rats by injection of e coli lipopolysaccharide extracts , and in the skin of pigs by subcutaneous injection of rhodococcus equi .
the microscopic appearance of these lesions , and the identification of e coli within them has been compared with e coli - associated granulomatous colitis in boxers and french bulldogs .
a recent study of affected boxers and french bulldogs revealed genetic polymorphisms in a region of chromosome 38 , which includes loci encoding signalling lymphocytic activation molecule family glycoproteins ; these have been linked to impaired killing of e coli , consistent with the proposed pathogenesis of malakoplakia .
this report describes a case of malakoplakia involving the vagina of a young cat ; a novel location for the disease in animals , the first report describing intracellular e coli associated with feline malakoplakia , the second report of successful treatment of this disease , and also the first report of successful treatment with enrofloxacin .
a 3-year - old , female , spayed , domestic shorthair cat was presented to the primary veterinary clinic for malaise , anorexia , stranguria , periuria , pollakiuria and macroscopic haematuria .
the cat had no previous pertinent medical history , and had been spayed at 5 months of age , with no abnormalities or complications noted during or after surgery .
no abnormalities were noted on clinical examination , and the cat was prescribed an empirical 6 day course of amoxicillin / clavulanic acid tablets at 12.5mg / kg q12h ( clavulox ; zoetis animal health ) .
a cystocentesis sample revealed well - concentrated urine ( specific gravity 1.050 ) , with microscopic haematuria and trace protein noted on dipstick evaluation .
was seen protruding from the vulva ; a grab biopsy sample of this tissue was collected under general anaesthesia .
pending histopathology the cat was prescribed prednisone orally at 5 mg q12h for 7 days , reducing it to 5 mg q24h for 7 further days and further amoxicillin / clavulanic acid at the previous dose .
histopathology at a reference laboratory ( new zealand veterinary pathology , hamilton ) revealed dysplastic squamous epithelium , with moderate numbers of neutrophils , macrophages and activated fibroblasts , resulting in a diagnosis of chronic granulomatous and proliferative vaginitis with marked epithelial dysplasia . despite initial improvement with the new treatment regime , malaise , lethargy , vaginal swelling , macroscopic haematuria and periuria persisted , and so the cat was referred to an internal medicine specialist for further evaluation . on presentation to the veterinary specialist group , the sole abnormality noted on physical examination was a small , fleshy , erythematous mass protruding from the vaginal vault .
feline immunodeficiency virus and feline leukaemia virus elisas were negative ( snap fiv / felv combo ; idexx laboratories ) .
abdominal ultrasound ( ie35 , c8 - 5 probe ; philips ) identified free - floating and slowly settling echogenic debris and a single , 2.7 mm diameter mineralised structure revealing gravity dependence within the urinary bladder .
imaging from a perineal window identified a vaginal mass effect greater than 3 cm in size with mixed echogenicity , a hyperechoic centre and a hypoechoic periphery ( figure 1 ) .
the caudal limits of the lesion had a bulbous shape while the cranial limits revealed a thickened fusiform shape .
longitudinal view of the vaginal mass , with calipers demonstrating the craniocaudal extent of the lesion .
white arrows indicate the location of the lesion vaginoscopy , performed under general anaesthesia using a 3.5 mm rigid endoscope ( 64019 ba , 1030340 camera , dx pal 202420 - 20 processor ; karl storz ) identified an extensive , fleshy , friable , irregularly shaped mass with diffuse attachment to the mucosa within the vaginal vault .
thick , firm , white exudate was present , particularly around the cranial aspect of this lesion .
extensive debridement and biopsy of abnormal tissue was performed with 2.8 mm round - cup biopsy forceps ( fb-35c-1 ; olympus ) .
the urethral orifice was not visible ; however , a urinary catheter was passed blindly to ensure urination after mass debridement .
culture of the fresh tissue at a reference laboratory ( gribbles veterinary , auckland ) produced a heavy growth of e coli , sensitive to amoxicillin / clavulanic acid , cephalothin , enrofloxacin , trimethoprim sulpha , polymyxin b and neomycin by standard disc diffusion testing .
the cat was hospitalised with the urinary catheter in situ for 48 h , and then discharged with no complications noted . in the light of the culture , sensitivity and histopathology results , enrofloxacin ( baytril ; bayer animal health ) was prescribed at a dose of 5 mg / kg q24h for 6 weeks .
this resulted in rapid and complete resolution of the clinical signs and the cat is clinically normal 1 year after treatment .
the biopsy samples were fixed in 10% neutral buffered formalin before routine histological processing and embedding in paraffin wax .
on histopathological examination the biopsies were well preserved , and lined by dysplastic squamous epithelial cells ; similar cells also formed cords , islands or glandular / ductular structures infiltrated by neutrophils within the samples ( presumed dysplastic vestibular glands ) .
the adjacent stroma was heavily and diffusely infiltrated by neutrophils , lymphocytes and plasma cells admixed with many macrophages ( figure 2 ) .
these had abundant , faintly granular eosinophilic cytoplasm , with variably strong pas - positive staining ( figure 3 ) .
the macrophages sometimes contained a neutrophil , vacuolated space or short bacterial rods , found to be gram - negative on gram staining ( figure 4 ) ; similar rods were also seen apparently within neutrophils .
no basophilic bodies were seen within macrophages on haematoxylin and eosin or von kossa stains .
faint basophilic objects consistent with bacterial rods are visible in macrophages ( see inset , indicated by white arrow ) .
schiff - positive granules ( pas ,  50 ) macrophages contain gram - negative bacterial rods ( see inset , indicated by white arrow ) .
gram stain ,  100 unstained sections ( 5 m on charged glass slides ) of formalin - fixed , paraffin - embedded tissue were submitted to cornell university for fluorescence in situ hybridisation ( fish ) analysis with a eubacterial probe and an e coli probe as described previously .
specificity of hybridisation was controlled by co - hybridisation with an irrelevant labelled probe ( non - eub-338 [ actc - ctacgggaggcagc-6-fam ] ) , and the use of control slides of cultured e coli , streptococcus species and proteus species .
hybridised samples were washed in phosphate - buffered saline , allowed to air dry and mounted with a prolong antifade kit ( molecular probes ) .
sections were examined on an axioskop 2 ( carl zeiss ) or a bx51 ( olympus america ) epifluorescence microscope , and images were captured with a zeiss axiocam or olympus dp-7 camera , respectively .
multifocal clusters of short- and medium - sized rods that hybridised with eubacterial probe 338 were visualised within cells that were consistent with macrophages within mucosa .
these bacteria also hybridised with e coli / shigella species probe , indicating the presence of intramucosal infection with e coli ( figure 5 ) .
eubacterial fish revealed multifocal clusters of intracellular rods within the vaginal mucosa ( arrows ) .
this is the first reported feline case of malakoplakia with vaginal involvement , intracellular e coli and successful treatment with a fluoroquinolone .
reports to date suggest that malakoplakia is an important differential diagnosis for lower urinary tract disease in a young cat , especially when a granulomatous mass is identified involving the urogenital system and , especially as these reports illustrate that this condition is treatable , in contrast to comments from another source .
this case had pas - positive macrophages and invasive gram - negative bacteria but did not have the michaelis 
. however , their absence does not preclude a diagnosis of malakoplakia as they are not uniformly present or easily detected in malakoplakia in people or animals .
smith described three stages of malakoplakia lesion development in humans , with the first ( early ) stage characterised by plasma cells , macrophages , eosinophils and an absence of michaelis  gutmann bodies .
an experimental study involving the injection of e coli into the kidneys and testes of rats produced lesions resembling those described in smith s stages , with michaelis 
gutmann bodies appearing later in the disease process . garrett and mcclure had similar findings but suggested an alternative explanation that the dose of e coli stimulus dictated whether or not michaelis  gutmann bodies formed .
in this case , the lesion location ( close to the urethral orifice ) , microscopic appearance , presence of e coli and response to therapy lead to the diagnosis of pyogranulomatous vaginitis / vestibulitis consistent with malakoplakia .
however , further investigation and treatment was directed at the obvious mass present in the vagina , with a plan to address the urinary bladder if the clinical signs did not resolve .
the microscopic appearance of these lesions , and the identification of e coli within them has been compared to whipple s disease of humans , and granulomatous colitis of boxers and french bulldogs .
it is relevant to this case that pas - positive macrophages are found in granulomatous colitis , but invasive bacteria are rarely seen on routine histopathology , and michaelis  gutmann bodies have not been reported in those lesions .
intracellular bacteria were not identified in the two case studies in cats , although e coli was cultured from the bladder wall and urine of one kitten .
fish was performed in this case , in addition to gram staining and histopathology , to confirm the presence of intracellular bacteria .
successful treatment with long courses of antibiotics capable of penetrating macrophages is common in human malakoplakia , and has recently been reported in one of the kittens with urinary bladder lesions .
the second reported feline case , also in the urinary bladder , was diagnosed post mortem .
it is interesting to note that the cat described herein was initially unsuccessfully treated with antibiotics to which the organism was susceptible in vitro .
this is similar to a previous cat , which eventually responded to sulfamethoxazole and trimethoprim , in conjunction with amoxicillin and clavulanic acid .
antibiotics other than fluoroquinolones , or trimethoprim / sulfamethoxazole , have not been effective in human medicine .
it has been hypothesised that penetration of antibiotics into macrophages may be important in treatment success in people , and fluoroquinolone antibiotics are known to achieve this .
one review of the human literature suggested long courses of fluoroquinolone antibiotics have a cure rate of 90% .
the importance of combining antimicrobial sensitivity with the ability to penetrate macrophages is pivotal for successful treatment of e coli - associated granulomatous colitis in boxers .
this is in contrast to humans , where the average age of presentation is > 50 years , and 40% of people have concurrent systemic illness .
we are aware of another case of malakoplakia recently diagnosed in christchurch , new zealand , in the urinary bladder of a 3-month - old kitten ( r fairley , 2016 , personal communication ) , suggesting that malakoplakia is more common in young cats than previously thought .
a survey of pathologists showed a low rate of correct identification of the classic histological appearance of this disease in people , which may also be the case in domestic animals , resulting in misdiagnosis .
this report provides further evidence that malakoplakia is a treatable disease that needs to be considered as a differential diagnosis for lesions within the urogenital tract of cats , especially if young .
this case report describes a unique presentation , and the first case of malakoplakia outside of the urinary bladder in a cat , and the first responding to enrofloxacin .
further study would be beneficial to clarify the pathogenesis and prevalence of this disease , along with optimal treatment strategies .
 case summarya 3-year - old , female , spayed , domestic shorthair cat presented for dysuria and haematuria , unresponsive to antibiotic treatment . 
 a small , fleshy , erythematous mass protruded from the vaginal vault . 
 ultrasound identified a vaginal mass effect with mixed echogenicity measuring in excess of 3 cm . 
 vaginoscopy confirmed an extensive , fleshy , irregular mass that was characterised histologically as pyogranulomatous vaginitis , with periodic acid  
 schiff - positive macrophages containing gram - negative bacteria . 
 fluorescence in situ hybridisation analysis demonstrated invasive intracellular escherichia coli . 
 vaginal malakoplakia was diagnosed . 
 tissue culture and antimicrobial susceptibility of e coli was used to guide treatment . 
 a 6 week course of enrofloxacin 5 mg / kg q24h resulted in complete resolution of the mass and clinical signs.relevance and novel informationmalakoplakia is a rare chronic inflammatory condition that has been previously reported in the bladder of two cats . 
 the pathogenesis of malakoplakia is thought to involve ineffective killing of bacteria ( eg . 
 e coli ) , similar to granulomatous colitis in boxers and french bulldogs . 
 the literature on malakoplakia in cats is sparse . 
 this is the first reported feline case with vaginal involvement , intracellular e coli and successful treatment with a fluoroquinolone . 
 malakoplakia is an important , non - neoplastic differential diagnosis when a mass is identified in the urogenital system of a young cat . 
Case summary
Relevance and novel information
Introduction
Case description
Discussion
Conclusions