JPC SYSTEMIC PATHOLOGY

URINARY SYSTEM

January 2024

U-P10

 

Signalment (AFIP #1184029): Rat.

 

HISTORY: Clinically normal.

 

HISTOPATHOLOGIC DESCRIPTION: Urinary bladder: Diffusely, the urothelial cells pile up to 10 cell layers thick (hyperplasia) with loss organization (dysplasia). Multifocally within the urothelium there are multiple cross and tangential sections of adult nematodes and rare eggs surrounded with attenuated overlying epithelium. Adult nematodes are 150-200 µm in diameter, with a smooth cuticle, polymyarian-coelomyarian musculature, a pseudocoelom, bacillary bands, a large intestine lined by numerous uninucleate cells, and a prominent, thick-walled uterus which often contains several developing and larvated eggs which are oval, approximately 40 x 70 µm, bi-operculate with a golden-brown anisotropic shell. There are few lymphocytes, macrophages, and rare neutrophils within the lamina propria. Multifocally within the lumen, there is an abundant amount of deeply eosinophilic granular to flocculent material admixed with hemorrhage.

 

Salivary glands (parotid, submandibular and sublingual); mandibular lymph node; prostate gland; coagulating glands; seminal vesicles; vas deferens; and urethra: Essentially normal tissue.

 

MORPHOLOGIC DIAGNOSIS:  Urinary bladder: Urothelial hyperplasia, multifocal, mild, with mild lymphohistiocytic cystitis, and intraepithelial and luminal adult nematodes and eggs, rat, rodent.

 

ETIOLOGIC DIAGNOSIS:  Urinary trichosomoidiasis

 

CAUSE:  Trichosomoides crassicauda (Bladder threadworm)

 

GENERAL DISCUSSION: 

• Member of order Enoplida under the Aphasmid group and phylogenetically related to Trichuris sp., Trichinella spiralis, and Calodium hepaticum  
• Only known hosts are Rattus norvegicus and R. rattus; occurs in wild rats and rarely, in laboratory rats, females overrepresented (Rothenburger et. al, J Vet Diagn Invest, 2019)
• Reside in the urinary bladder, ureters or renal pelvis
• Bi-operculate larvated eggs are shed in the urine in bunches, and are held together by an adhesive that also helps them to stick to surfaces in the environment
• Eggs remain infective for long periods; direct contact with infected rats appears to be required for natural transmission; intra-cage transmission readily occurs
• Important because of potential confusion over parasite induced lesions versus chemically induced urothelial changes in toxicological studies (N-methylnitrosourea (MNU))

 

PATHOGENESIS:

• Migrating larvae in the lungs may result in multifocal granulomas and eosinophilia 
• Peripheral blood eosinophilia is common during larval migration  
• Often non-pathogenic, but adult worms may cause urinary calculi, bladder papillomas and possibly urothelial carcinoma 

 

LIFE CYCLE:  

• Direct: Ingested embryonated eggs voided from the urine hatch in the stomach > larvae penetrate gastric wall > migrate to the portal vein > heart, lungs, other parts of the body > break through the wall of submucosal vessels in the urinary bladder, renal pelvis, ureters > migrate to lumen > mature to adults (prepatent period is 50 to 60 days)  
• Females partially burrow into the mucosa
• Males are capable of freely moving and relocating, and occasionally more than one male will reside within a single female  

 

TYPICAL CLINICAL FINDINGS:

• Usually asymptomatic
• Pulmonary hemorrhages and granulomas 
• Peripheral blood eosinophilia 

 

TYPICAL GROSS FINDINGS:

• Threadlike worms up to 10 mm long either free in the bladder lumen or with anterior end embedded in the mucosa 
• Focal white thickenings and masses on the mucosal surface
• Focal hemorrhages in the lungs, liver, and kidneys during larval migration; may cause granulomatous lesions in lungs 
• Retarded growth and rough hair coat

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Female worms are embedded in the mucosa or free in the lumen while males are typically free in the lumen
• Aphasmid nematode: Adults are 100-200 um in diameter, have polymyarian coelomyarian musculature, bacillary bands, stichosome esophagus, pseudocoelom, intestine with numerous uninucleate cells, and a male or female reproductive tract
• Eggs are thick walled, golden brown, bi-operculated and larvated 

• Increased leukocytes in the bladder mucosa
• Mucosal erosions and epithelial hyperplasia

• Migrating larvae in and around blood vessels in the kidney, ureters, and bladder, as well as other organs, especially the lungs
• Congestion, hemorrhage and granulomas in the lungs

 

ADDITIONAL DIAGNOSTIC TESTS:

• Examination of urine filtrate for eggs
• Light microscopy, EM, frozen sections stained with acridine orange

 

DIFFERENTIAL DIAGNOSIS:

• Definitive diagnosis is made by identifying worms in tissue sections or eggs in urine 
• Must differentiate parasite induced urothelial hyperplasia and papillomas from those induced by chemicals used in toxicological studies

 

COMPARATIVE PATHOLOGY:  

• Dogs and cats: Pearsonema (Capillaria) plica, P. feliscati - attach to renal pelvis, ureter and bladder; cause hemorrhage and cellular infiltrates

• Intraepithelial nematodes:

• Gongylonema sp.: Esophagus; affects ruminants, pigs, horses, nonhuman primates, and occasionally rodents 

• Anatrichosoma sp. (I-P05): Nasal mucosa of nonhuman primates
• Trichosomoides crassicauda: Urothelium of rats
• Eucoleus boehmi: Nasal mucosa of dogs
• Eucoleus aerophilus: Respiratory parasite

 

REFERENCES:

1.  Barthold SW, Griffey SM, Percy DH.  Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: John Wiley & Sons; 2016:152-153.

2.  Frazier KS, Seely JC, Hard GC et al.  Proliferative and nonproliferative lesions of the rat and mouse urinary system. Toxicol Pathol. 2012; 40(S): 14-86. 

3.  Rothenburger JL, Himsworth CG, La Perle KMD, Leighton FA, Nemeth NM, Treuting PM, Jardine CM. Pathology of wild Norway rats in Vancouver, Canada. J Vet Diagn Invest. 2019;31(2):184-199.

4.  Taylor MA, Coop RL, Wall RL. Veterinary Parasitology. 4^th ed. West Sussex, UK: John Wiley and Sons; 2016: 849.

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