JPC SYSTEMIC PATHOLOGY

URINARY SYSTEM

January 2024

U-P05 (NP)

 

Signalment (JPC# A75-40-2): Puppy

 

HISTORY: Incidental finding from a puppy killed by a car.

 

HISTOPATHOLOGIC DESCRIPTION: Kidney (2 sections): Multifocally, effacing less than 5% of renal cortex and compressing adjacent tubules, there are variably sized granulomas. The granulomas are up to 300 µm in diameter, have a central core of necrosis surrounded by epithelioid macrophages, which are further bounded by lymphocytes, plasma cells, occasional eosinophils, fibroblasts, fibrous connective tissue, and occasional multinucleated giant cells (foreign body and Langhans type).  Occasionally, the granulomas center on cross and tangential sections contain an often poorly discernible nematode larva. Larval nematodes are 40 µm in diameter with a 2 µm eosinophilic cuticle, and large lateral cords that fill the pseudocoelom. Within the renal interstitium, there are multifocal aggregates of low numbers of lymphocytes and plasma cells. Multifocally, scattered tubules are ectatic and lined by attenuated epithelium. The subcapsular surface is mildly irregular and undulant.

 

MORPHOLOGIC DIAGNOSIS: Kidney: Granulomas, multiple with mild multifocal lymphoplasmacytic interstitial nephritis and nematode larva, breed unspecified, canine.

 

ETIOLOGIC DIAGNOSIS: Renal toxicariasis

 

CAUSE: Toxocara canis

 

GENERAL DISCUSSION:

• Toxocara sp. are Ascarid nematode parasites, which are some of the most common intestinal parasites in birds and Mammals; most are host specific and rarely develop to maturity in species other than their true host; eggs remain infective in soil for years
• T. canis granulomas are the most common parasitic lesion in the kidneys of dogs:
  1. Focal areas of inflammation and scarring are occasionally observed as incidental lesions
  2. Renal function is rarely affected, even when numerous larvae are present

 

PATHOGENESIS 

• Four possible modes of infection: Ingestion (of embryonated eggs), in utero, transmammary infection, and ingestion of a paratenic host (e.g., rodents, rabbits)

• After ingestion the parasite’s larval sheath, feces, and saliva are antigenic

 

LIFE CYCLE

• After ingestion of embryonated ova, larvae penetrate intestinal mucosa -> Migrate via the liver to arrive in the lungs -> Larvae then follow one of two different pathways (depending on age and immune status):
  1. Tracheal migration: Larvae penetrate alveoli ->Trachea -> Coughed up and swallowed -> Mature into adults in intestine (produces patent infection)
  2. Larval migrans: Larvae penetrate alveoli -> Distributed by the circulatory system throughout the body to encyst (non-patent infection)
     • Commonly end up in kidneys, skeletal muscle, liver and central nervous system
     • Visceral larval migrans (VLM): If aberrant or dead-end hosts ingest embryonated eggs from the environment or infective larva, larvae can migrate into variety of tissues including the eyes (ocular larva migrans)
       • Some sources (e.g., JKP) separate VLM in aberrant hosts with larval migrans in the dog
       • VLM is more common in older animals and there is generally greater damage created in an aberrant host
• In utero transplacental infection: In pregnant bitch, encysted larvae are reactivated within the last 7-10 d of gestation-> Migrate to placenta > To liver of fetus > To lungs just after birth > > intestine (via trachea) > final molts
  1. The most important route of infection in young dogs is transplacental transmission

 

TYPICAL CLINICAL FINDINGS:  

 

TYPICAL GROSS FINDINGS:   

• Granulomas randomly scattered throughout kidneys, but primarily in the cortex
• Lesions initially are small 2-3 mm gray-yellow foci with soft centers; later, these areas become firm and white with pitting of the cortical surface
• Other lesions caused by migrating larvae include focal hemorrhages in lungs and granulomas in various tissues; in the eyes, there may be retinitis or post-inflammatory retinopathy
• Large numbers of maturing worms in intestine

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Small granulomas (2-3 mm in diameter) surround entrapped larva (may be difficult to find in sections) and are composed of epithelioid macrophages and lymphocytes with occasional eosinophils, surrounded by fibroblasts within concentrically arranged fibrous connective tissue; randomly scattered throughout the subcapsular renal cortex
• As larvae die, the become fragmented, and the debris is either phagocytosed and eliminated or retained with a resultant granulomatous response and fibrosis (Residual scar > dense concentrically arranged fibrous tissue)

 

ADDITIONAL DIAGNOSTIC TESTS: 

 

DIFFERENTIAL DIAGNOSIS:

Granulomatous nephritis:

• Encephalitozoon cuniculi - lymphoplasmacytic to granulomatous nephritis in puppies with systemic infections
• Xanthogranulomas - dogs with hypothyroidism and severe atherosclerosis; foamy, lipid-laden macrophages, lymphocytes, plasma cells, and fibrosis interspersed with cholesterol clefts
• Fungi: Aspergillus sp., Phycomycetes, Histoplasma capsulatum
• Algae: Prototheca sp.
• Bacteria: Mycobacterium sp. - granulomas up to 10 cm in diameter; central area of necrosis surrounded by epithelioid macrophages and giant cells that contain acid-fast bacteria

 

COMPARATIVE PATHOLOGY:

• Ascaridae
  1. Cat, lion, leopard: Toxocara cati > Produce similar residual scar as T. canis
  2. Dog, cat, lion, tiger, fox: Toxascaris leonina
  3. Cattle and water buffalo: Toxocara vitulorum > Produce similar residual scar as T. canis  
  4. Horse: Parascaris equorum
  5. Chickens, turkeys: Ascaridia galli
  6. Flying foxes: Toxocara pteropodis 
• Halicephalobus gingivalis (N-P11) may produce granulomas in the kidneys, nasal cavity, or cerebrum of horses

 

REFERENCES

1. Buckle KN, Hardcastle MR, Scott I, et al. Toxocara canis Larval Migration Causing Verminous Pneumonia in Fading Puppies From 2 Scottish Terrier Litters. Vet Pathol. 2019;56(6):903-906. 
2. Conrado FO. Fecal and Rectal Cytopathology: Raskin RE, Meyer DJ, and Bowes KM. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023:378. 
3. Cianciolo RE, Mohr FC. Urinary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:442.
4. Farina LL, Lankton JS. Chiroptera. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:607-632. 
5. Haddad JL, Marks Stowe DA, Neel JA. The Gastrointestinal Tract. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:305-306. 
6. Labelle P. The Eye. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1423.
7. Miller AD, Porter, BF. Nervous System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:931.
8. Spagnoli ST, Gelberg HB. Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:435. 
9. Sula MM, Lane LV. The Urinary System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:742.
10. Uzal FA, Plattner BL, Hostetter JM. Digestive system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed.  Philadelphia, PA: Elsevier; 2016:219-220.
11. Valentine BA. Skeletal Muscle. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1007.e1.

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