JPC SYSTEMIC PATHOLOGY

URINARY SYSTEM

January 2024

U-V05

 

Signalment (JPC #3106379 / WSC 08-09 conference 14; case 2): Juvenile, female, Mahogany, (Mustela vison), mink.

 

HISTORY: None provided.

 

HISTOPATHOLOGIC DESCRIPTION: Kidney: Diffusely, glomerular capillary lumina are often indistinct, and glomeruli exhibit one or more of the following changes:  increased cellularity of the mesangium, increased eosinophilic hyaline material within the mesangium and/or glomerular basement membrane (hyalinosis or sclerosis), segmental to global replacement by eosinophilic cellular and karyorrhectic debris (necrosis) admixed with occasional hemorrhage and rare neutrophils, or segmental to global replacement of glomerular tuft components by mesangial matrix, sclerotic collagen and/or fibrous connective tissue (sclerosis). Multifocally, the parietal epithelium of Bowman’s capsule is hypertrophied. Tubular epithelium is often either pale, swollen, vacuolated (degenerative), shrunken and hypereosinophilic (necrotic), or rarely has increased basophilia with plump, vesiculate nuclei (regenerative). The interstitium contains multifocal infiltrates of abundant lymphocytes and plasma cells that occasionally replace tubules. Multifocally, the tunica media of small to medium-sized arterioles is thickened by eosinophilic hyaline material admixed with hemorrhage and edema (fibrinoid vasculitis), and are transmigrated and surrounded by variable numbers of lymphocytes and plasma cells. In the tunica intima the endothelium is hypertrophied or effaced and replaced by fibrin and debris. Multifocally there are ectatic lymphatics and increased clear space (edema).  

 

Urinary bladder: Diffusely, arterial walls are replaced with a hypereosinophilic hyaline material with multifocal cellular debris and are surrounded by abundant lymphocytes, plasma cells, few macrophages, eosinophils, and fibrosis. 

 

MORPHOLOGIC DIAGNOSIS: Kidney: Glomerulonephritis, membranoproliferative (presumptive), diffuse, moderate, with multifocal fibrinonecrotizing arteriolitis, lymphoplasmacytic interstitial nephritis, and tubular degeneration and necrosis, mink (Mustela vison), mustelid.

 

Urinary bladder: Arteritis, fibrinonecrotizing, diffuse, severe, with perivascular lymphoplasmacytic cystitis.

 

ETIOLOGIC DIAGNOSIS: Parvoviral glomerulonephritis and arteritis.

 

CAUSE: Aleutian mink disease virus (Amdovirus, ADV, AMDV)

 

SYNONYMS: Aleutian mink disease, mink plasmacytosis

 

GENERAL DISCUSSION:

• Single-stranded DNA virus; family Parvoviridae, genus Amdoparvovirus (previously Amdovirus), species Carnivore amdoparvovirus 1; there are several strains with variable virulence 
• Disease of farm-raised mink; a disease of financial importance worldwide

• Disease signs vary with the age and coat color of mink, as well as strain of virus

• 4 viral strains recognized: Utah-1, Ontario, Montana, and Pullman
• Coat color: Mink homozygous for the Aleutian gene (blue coat color) are especially susceptible, heterozygous individuals are less severely affected, and mink lacking this gene are susceptible but may carry and excrete the virus for years without clinical signs 

• The Aleutian gene is linked to a gene responsible for a lysosomal abnormality  (Chediak-Higashi syndrome, see U-M02) of granulocytes, which inhibits destruction of phagocytized immune complexes
• Chediak-Higashi syndrome is presumed to be a defect in the lysosomal trafficking gene (LYST) that results in defective melanosomes, lysosomes, platelet-dense granules, and cytolytic granules in many cell types, including melanocytes, neutrophils, monocytes, natural killer lymphocytes, and platelets

 

PATHOGENESIS:

• Parvoviruses are dependent on the S-phase of the host cell cycle for virus replication, and therefore induce greatest cytolytic disease in tissues with a high mitotic rate, including lymphoid tissues undergoing antigenic stimulation; virus localization is limited to certain cell types that bear the appropriate viral receptors
• Virus is shed in saliva, urine, and feces; transmission is via inhalation or ingestion; vertical transmission is mainly responsible for maintaining the virus in a population in the wild (mink are normally solitary animals) 
• Virus replicates and becomes sequestered in macrophages and dendritic cells; abundant viral antigen usually found in Kupffer cells and lymphoid organs
• In adults, strong humoral immune response is elicited à increased gamma globulins; with persistent infection, persistent antigenic stimulation à antigen-antibody complex deposition (type III hypersensitivity)à clinical signs (e.g. immune-complex glomerulonephritis and arteritis); in older mink, death is attributed to glomerulonephritis or secondary infection following immunosuppression
• In young animals (kits), virus has cytocidal effect on pneumocytes and disease manifests as an acute interstitial pneumonia (P-V14)

 

TYPICAL CLINICAL FINDINGS:

• Kits: Acute pneumonia à lethargy, increasingly labored breathing, unconsciousness, death
• Adults: Hypergammaglobulinemia (usually >20% of total serum protein), plasmacytosis, lethargy, anorexia, cachexia, polydipsia, fever, blood exuding from the mouth and anus; in persistently infected mink, infertility and abortion

 

TYPICAL GROSS FINDINGS:  

• Kits: Noncollapsing, patchy to diffusely red lungs; hepatomegaly, splenomegaly
• Adults: Splenomegaly and/or splenic congestion; lymphadenopathy; hepatomegaly and/or hepatic chronic passive congestion; gingivitis; oral ulcers; multiple hemorrhages; arteritis; enlarged pale yellow kidneys with petechiae, pitting, or atrophy

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Adults: Immune-complex glomerulonephritis and arteritis; plasma cell infiltrates in the renal interstitium, hepatic portal areas, and red pulp of the spleen; bile duct proliferation; multifocal lymphocytic infiltrates are common and tentatively diagnostic
• Kits: Acute interstitial pneumonia with type II pneumocyte hyperplasia, hyaline membrane formation, +/- amphophilic intranuclear inclusion bodies
• Large basophilic to amphophilic intranuclear inclusion bodies have been described in type II pneumocytes of experimentally inoculated mink, and have been described in renal tubular epithelial cells in striped skunks

 

ULTRASTRUCTURAL FINDINGS:  

 

ADDITIONAL DIAGNOSTIC TESTS:  

• Counter-immunoelectrophoresis (CIEP) testing remains the gold standard for AMDV diagnosis, especially in large captive facilities
• PCR, in-situ hybridization, IFA, radioimmunoassay, complement fixation, ELISA

 

DIFFERENTIAL DIAGNOSIS:

 

COMPARATIVE PATHOLOGY:  

Amdoparvoviruses in other species:

• First discovered in mink, later in domestic ferrets and wild mustelids (striped skunk)
• Ferrets: 

• Ferret-derived strains are different from mink-derived strains; although the mink strains of ADV can infect ferrets, there are several strains that are more commonly found in ferrets that are of lower virulence in mink
• Disease is similar but more insidious (chronic, progressive) than in mink 
• Other reported disease presentations include: liver failure, intestinal disease including melena, and central nervous system disease

• Striped skunks
• Red pandas

Other parvoviruses in other species: Parvovirus in many species targets crypt epithelium of the small intestine, resulting in intestinal disease; rodent parvoviruses do not target intestinal epithelium

• Porcine parvovirus: Stillbirth, abortion, fetal death, mummification, and infertility

• Feline panleukopenia virus (feline distemper): Affects all felids, mink, raccoons, and some other procyonids; generalized disease in kittens, with panleukopenia, enteritis; cerebellar hypoplasia

• Dog:

• Canine parvovirus 1: Minimal disease
• Canine parvovirus 2: Generalized neonatal disease; enteritis, nonsuppurative myocarditis (rare, 2-8 weeks old pups), lymphopenia

• Bovine parvovirus (BPV 1-3): Unclear status as pathogen, possible cause of neonatal diarrhea and adult respiratory/reproductive disease 

• Rat: Subclinical infections common

• Toolan H-1 virus, Rat Minute Virus, Rat Parvovirus
• Rat Virus/Kilham’s Rat Virus (RV): The most pathogenic of the rat parvoviruses, may be the only to cause natural disease; causes lymph node congestion, body fat loss, scrotal hemorrhage, +/- splenomegaly, icterus, ascites, CNS hemorrhagic foci, focal hepatocellular necrosis and intranuclear inclusion bodies, cerebellar hypoplasia; upon recovery, liver may have focal angiectasis (peliosis hepatis) and nodular hyperplasia

• Mouse:

• Minute virus of mice (MVM): Lymphocyte and endothelial tropism; dwarfism, cerebellar hypoplasia; disease is limited in duration with recovery in immunocompetent mice
• Mouse Parvovirus (MPV): Lymphocyte tropism; predominant parvoviral infection of mice (compared to MVM); infection is typically persistent

• Hamster parvovirus (possibly mouse parvovirus-3): Report of epizootic outbreak in suckling and weanling hamsters resulting in marked discoloration, malformation, and absence of incisor teeth, periodontitis, suppuration with mineralization and hemorrhage in the dental pulp, as well as domed calvarium and potbellied appearance

• Rabbit (Lapine parvovirus): Typically clinically normal
• Goose parvovirus: Hepatitis, myocarditis, myositis
• Duck parvovirus: Hepatitis, myocarditis, myositis
• Chicken and turkey parvovirus: Enteritis

 

REFERENCES:  

1. Alex CE, Watson KD, Schlesinger M, Jackson K, Mete A, Chu P, Pesavento PA. Amdoparvovirus-associated disease in striped skunks (Mephitis mephitis). Vet Pathol. 2023;60(4):438-442.
2. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016: 17-19, 122-124, 175-176, 196, 259.
3. Snyder PW.  The Urinary System. In: Zachary JD, ed., Pathologic Basis of Veterinary Disease.7th ed. St. Louis, MO: Elsevier; 2022: 727.
4. Sula MM, Lane LV.  The Urinary System. In: Zachary JD, ed., Pathologic Basis of Veterinary Disease.7th ed. St. Louis, MO: Elsevier; 2022: 330, 337.
5. Uzal FA, Plattner BL, Hostetter JM.  Alimentary system.  In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals.  Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:153-158.
6. Williams BH, Burek Huntington KA, Miller M. Mustelids. In: Terio KA, McAloose D, St. Leger J. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018: 554-296.

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