like human beings , the incidence of bladder stone or urolithiasis is a common finding in domestic animals such as dogs and cats . in laboratory animals such as mice and rats , sporadic and outbreak of kidney and bladder stone in laboratory rodents have been reported earlier , and the most of them have been linked to dietary ingredients . intravesical obstructions , such as prostatic hyperplasia and neurogenic bladder are two known risk factors for bladder stone in elderly men . several other predisposing factors are also responsible for formation of bladder stones in humans and animals , that is , chronic urinary tract infection ( uti ) , presence of intravesical foreign substances , bladder diverticula , and upper urinary tract stones . in a rat experimental model , moreover , rats have been used to develop a spinal cord injury animal model for the study of bladder stones . animals with bladder stone may display dysuria , irritating urine voiding symptoms , and macroscopic hematuria . to understand the role of bacterial infection in prostate cancer pathogenesis ; currently , we are conducting multiple animal studies . mostly , we are using copenhagen rats for our experimental studies . with the permission of institutional animal ethical committee ; till date , we have already received and used more than thirty adult male copenhagen rats . coincidentally , among the animals that we had received for our study , one animal had lethargic posture and rough body coat . while holding the animal , we notice a nodular solid mass inside the abdomen of the animal . from the exterior palpation , it was difficult to know the exact origin or location of the solid mass . therefore , with the consultation of veterinarian in - charge of the animal house we decided to sacrifice the animal and conduct a thorough necropsy . upon excision of the ventral abdomen , there was a very few fecal material inside the stomach and intestine ; which , might be due to less food intake . palpation of the bladder was giving gritty feeling , and was clearly suggesting the presence of bladder stones . we excised prostate , seminal vesicle , and bladder together , and captured the photograph [ figure 1 ] . exploratory puncture of the seminal vesicle showed the presence of yellow caseous exudates with the purulent smell . the urinary bladder was highly stretched and had lost its tonicity . upon opening of the bladder the gross investigation clearly suggested this case as a complicated case of urinary bladder stone accompanied by urinary tract and accessory sex glands infection . to understand the histological changes that might have occurred due to these complications , bladder , prostate , and seminal vesicle tissues were separated from each other and fixed in buffered formalin . gross images of the rat bladder ( bl ) filled with multiple bladder stones ( st ) , seminal vesicles filled with caseous mass ( sv ) , and enlarged prostate ( pr ) microscopy of bladder tissue samples revealed transitional epithelium replaced by squamous epithelium ( squamous metaplasia ) and covered by laminated keratin [ figure 2 ] . there was an excessive accumulation of denudated keratin lamella inside the lumen , which is a typical feature of keratinizing desquamative squamous metaplasia ( kdsm ) . the stromal region had moderate inflammation compare to other organs ( prostate and seminal vesicle ) . the anterior and posterior prostate were processed separately , and histological analysis showed the presence of an excessive number of inflammatory cells in both anterior and posteriors glands [ figure 2 ] . the lumen of the prostatic glands and the surrounding stroma was filled with the inflammatory cells and debris . in posterior prostate , the denudated keratin lamella covered the inflammatory cells inside the lumen of the glands . at many places a similar type of alteration was also noticed in seminal vesicle [ figure 2 ] . the presence of more number of alpha smooth muscle actin expressing myofibroblast like cells , and deposition of excessive collage in the stromal region indicates its reactive nature and confirms prostatic fibrosis [ figure 3 ] . histology of bladder , seminal vesicle , anterior , and posterior prostate tissues stained with h and e. there is a distinct keratinizing desquamative squamous metaplasia of normal epithelium in all the organs ( arrow heads ) . excessive accumulation of denudated keratin lamella is clearly visible all - over the bladder lumen , and other organs also have keratin lamellae at many places of their lumens ( stars ) . lumens and surrounding stroma of prostate glands and seminal vesicles are filled with immune cells ( hashes ) . in the lumens of some prostate glands , the immune cells are covered with keratin lamellae ( star ) . in most of the prostate glands and some places of seminal vesicles , the epithelial cells , and basement membrane were totally destroyed by invading immune cells ( percentage ) histology of the posterior prostate tissue shows interstitial fibrosis . ( a ) h and e staining shows the presence of desquamated keratin lamella covering immune cells inside the lumens , and the presence of excessive immune cells in inside the stroma . ( b ) alpha smooth muscle actin immunohistochemistry shows the presence of multiple myofibroblast like cells in the stromal regions . , the urinary stone can promote further infection of other adjacent organs like prostate and seminal vesicles . in this particular case , it is difficult to figure out the origin of infection ; however , co - existence of bladder stone , prostitis and seminal vesiculitis might have mutually promoted each other . though dietary factors and genetic predisposition are some of the risk factors for bladder stone , but absence of this kind of complicacies in other animals of the same age group ( even older ) partially rules out this possibilities . however , further biochemical analysis of the uterine stones might have provided some important clues about the possible cause of stone formation . kdsm otherwise known as upper urinary tract leukoplakia or cholesteatoma is a very rare disease . the hyperkeratosis and squamous metaplasia noticed in almost all the epithelia is a natural protective event to withstand the harsh condition produced by urinary stone and/or infection - induced chronic inflammation . the etiology of kdsm includes the presence of chronic irritation / inflammation or secondary to vitamin a deficiency . though squamous metaplasia is nonmalignant in nature , but keratinizing squamous metaplasia of the bladder is a significant risk factor for bladder cancer . likewise , it has also been believed that under adverse conditions the normal columnar prostatic epithelial cells might undergo squamous metaplasia , which later on could form squamous cell carcinoma . however , more experimental evidences are required to justify this poorly established fact . there are reports that copenhagen rats could develop spontaneous prostate cancer . including our lab many other labs have used copenhagen prostate cancer cell lines that were originated from a spontaneous tumor . the spontaneous origin of a prostate tumor in rats and similar genetic makeup of the derived cancer cell lines with human prostate cancer cells suggests a similarity between the pathophysiology of this disease both in human and rats . metaplasia is known as the reversible replacement of one differentiated cell type with another mature differentiated cell type . metaplasia mostly occurs in response to chronic inflammation or irritation and leads to a change of original cells with cells that are capable enough to withstand the new adverse environment . metaplasia occurs due to reprograming of progenitor or stem cells that are present in the normal tissues . recently , a series of experiments have demonstrated that murine prostate basal and luminal cell lineage are independently sustained ( lineage restricted unipotent stem cells ) , and in rare cases some basal cells are capable of differentiate into luminal cells . , 2014 provides the experimental evidence that bacterial infection stimulates differentiation of basal cells to luminal cells . therefore , the metaplasia observed in the aforementioned rat prostate might have originated from basal cells or from the self - sustained luminal cells . kwon et al . , have used a mouse model of prostitis in which infection of mouse prostate ( c57bl/6 ) was induced with an uropathogenic escherichia coli strain , cp9 . in this model the authors have observed almost all kind of histopathological changes that we observed in the infected rat prostate tissue ( immune cell infiltration , expansion of myofibrobalst stromal cells , fibrosis , etc . ) ; however , no report has been made about the possible metaplastic changes in prostate epithelium . the infection could induce both hyperplasia and metaplasia of human and rodent cells . at the same time , both hyperplasia and metaplasia are two completely different cellular events . therefore , in future information about the factors that decide the fate of luminal cells upon chronic prostate infection might be interesting . taken together , this particular case has provided a hope that these strain of rats might be a nice model to induce infection - mediated prostatic metaplasia and observe its effect on the incidence of prostate cancer . copenhagen rats could develop spontaneous urinary bladder stones.urinary bladder obstruction in rats might get associated with prostate and seminal vesicle infection.chronic infection of the prostate might induce kdsm .
we report a very rare case of urinary bladder stone in a laboratory rat , which was associated with severe prostatitis and seminal vesiculitis . 
 importantly , the histopathological analysis revealed the rare variety of keratinizing desquamative squamous metaplasia of bladder , prostate , and seminal vesicle epithelium . 
 immunohistochemistry for alpha smooth muscle actin protein and aniline blue staining for collagen clearly showed interstitial prostate fibrosis . 
 the detail information about these findings and subsequent discussion are provided here .