JPC SYSTEMIC PATHOLOGY
URINARY SYSTEM
February 2018
U-V05

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

HISTORY:  None provided

HISTOPATHOLOGICIC 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, and 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 Amdovirus, with several strains of variable virulence; typically a disease of farm-raised mink (a disease of financial importance worldwide)
• Disease signs vary with viral strain and the age and coat color of mink
  • Viral strains: 4 recognized: Utah-1, Ontario, Montana, and Pullman
  • Mink coat color: Mink homozygous for the Aleutian gene (blue coat color, gene defect in lysosomal trafficking LYST gene resulting in Chediak-Higashi syndrome, see U-M02) are especially susceptible due to inhibited destruction of phagocytized immune complexes, heterozygous individuals are less severely affected, and mink lacking this gene defect are susceptible but may carry and excrete the virus for years without clinical signs

PATHOGENESIS:

• In general, all 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 (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:

• 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
• Kits: Acute pneumonia à lethargy, increasingly labored breathing, unconsciousness, death

TYPICAL GROSS FINDINGS: 

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

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: 

• Parvovirus: Icosahedral intranuclear viral particles 26-28nm in diameter forming paracrystalline arrays; chromatin usually clumped at the nuclear membrane

ADDITIONAL DIAGNOSTIC TESTS: 

• PCR, in situ hybridization, IHC, clinical pathology (hypergammaglobulinemia, plasmacytosis), counter-immunoelectrophoresis (CEP), IFA, radioimmunoassay, complement fixation, ELISA, virus isolation

DIFFERENTIAL DIAGNOSIS:

• Mink enteritis virus: Virus isolation may be necessary to differentiate

COMPARATIVE PATHOLOGY: 

ADV 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 (Vet Pathol. 2015)
• Multisystemic lymphoplasmacytic inflammation (interstitial nephritis, myocarditis, hepatitis, meningoencephalitis, pneumonia, splenitis)
• Immune complex deposition: Glomerulonephritis, multiorgan arteritis +/- fibrinoid necrosis
• Neurologic disease: encephalomalacia with cerebral microangiopathy

Other parvoviruses:  Parvovirus in many species targets crypt epithelium of the small intestine, resulting in intestinal disease, but 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 (underrecognized, important cause of myocardial damage in dogs), lymphopenia
• Bovine parvovirus (BPV 1-3): unclear status as pathogen, possible cause of neonatal diarrhea and adult respiratory/reproductive disease
• Mink:
• Aleutian disease virus
• Mink enteritis virus: Panleukopenia, severe hemorrhagic enteritis
• Rat: subclinical infections common
• Toolan H-1 virus, Rat Minute Virus, Rat Parvovirus
• Rat Virus/Kilham’s Rat Virus (RV): The most pathogenic, 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 calvaria 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. 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
2. Farid AH, Hussain I, Arju I. Detection of Aleutian mink disease virus DNA and antiviral antibodies in American mink (Neovison vison) 10 days postinoculation.  J Vet Diagn Invest. 2015:27(3):287-294.
3. Ford J, McEndaffer L, Renshaw R, Molesan A, Kelly K. Parvovirus infection is associated with myocarditis and myocardial fibrosis in young dogs.  Pathol. 2017;54(6): 964-971.
4. Kollias GV, Fernandez-Moran J.   In: Miller RE, Fowler ME.  Fowler’s zoo and wild animal medicine. Vol. 8.  St. Louis, MO: Elsevier; 2015: 484.
5. Kiupel M, Perpinan D. Viral diseases of ferrets.  In: Fox JG, Marini RP. Biology and diseases of the ferret.  3rd ed.  Ames, IA: Wiley; 2014: 461-467.
6. LaDouceur EEB, Anderson M, Ritchie BW, Ciembor P, Rimoldi G, Piazza M, Pesti D, Clifford DL, Gianniti F. Aleutian disease: an emerging disease in free-ranging striped skunks (Mephitis mephitis) from California.  Pathol. 2015;52(6):1250-1253.
7. Li L, Pesavento PA, Woods L, et al. Novel amdovirus in gray foxes. Emerg Infect Dis. 2011:17(10):1876-8.
8. MacLachlan NJ, Dubovi EJ, Eds. Fenner’s Veterinary Virology. 5th ed. San Diego, CA: Academic Press.  2017;245-257.
9. Nituch LA, Bowman J, Wilson PJ, Schulte-Hostedde AI. Aleutian mink disease virus in striped skunks (Mephitis mephitis): evidence for cross-species spillover.  Wildl. Dis.2015;51(2):389-400.
10. Quesenberry KE, Carpenter JW. Ferrets, Rabbits, and Rodents Clinical Medicine and Surgery. 3rd ed. St. Louis, MO: Elsevier; 2012: 48, 71-73, 135-136.
11. Snyder PW. Diseases of immunity. In: Zachary JD, ed., Pathologic Basis of Veterinary Disease.6th ed. St. Louis, MO: Elsevier; 2017: 266.
12. 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.
13. Wilson DJ, Baldwin TJ, Whitehouse CH, Hullinger G. Causes of mortality in farmed mink in the intermountain west, North America.  J Vet Diagn Invest. 2015:27(4):470-475.

 

 

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