JPC SYSTEMIC PATHOLOGY

CARDIOVASCULAR SYSTEM

March 2025

C-V01 (NP)

 

SIGNALMENT (JPC #2014367): A 5-week-old Labrador retriever

 

HISTORY: None

 

HISTOPATHOLOGIC DESCRIPTION: Heart: Multifocally, low numbers of cardiomyocytes are lost and replaced by loosely arranged, thin bands of edematous collagen, small amounts of fibrin, edema, and few lymphocytes and rare plasma cells. Adjacent cardiomyocytes are often shrunken with otherwise normal cell architecture (atrophy), are occasionally swollen and vacuolated (degeneration), or rarely are shrunken and fragmented with loss of cross striations and hypereosinophilic sarcoplasm (necrosis). Multifocally, low numbers of cardiomyocyte nuclei contain a 5-10µm diameter intranuclear inclusion body that is basophilic and completely fills the nucleus, or is eosinophilic and surrounded by a 1-2µm clear halo and marginated chromatin. Diffusely, the endomysial fibrous connective tissue is mildly expanded by clear space and eosinophilic proteinaceous fluid (edema).

MORPHOLOGIC DIAGNOSIS: Heart: Myocarditis, lymphoplasmacytic, chronic, multifocal, moderate, with cardiomyocyte atrophy, degeneration, and necrosis, and intranuclear viral inclusions, Labrador retriever, canine.

 

ETIOLOGIC DIAGNOSIS: Parvoviral myocarditis

 

CAUSE: Canine parvovirus 2 (CPV-2)

GENERAL DISCUSSION:

• Canine parvovirus is a common, often fatal, environmentally stable virus that can infect all canids and causes 3 distinct age-related clinical syndromes (see clinical findings below)
• Several antigenically distinct serotypes:
  • CPV-1 (Bocavirus; syn. Minute virus of canines): Causes myocarditis and respiratory diseases and intestinal enterocyte hyperplasia with eosinophilic to amphophilic intranuclear inclusion bodies (low/minimal pathogenic potential)
  • CPV-2 (subtypes 2a and 2b): Causes parvoviral enteritis (D-V02), myocarditis
• Rottweilers, Doberman pinschers, Labrador retrievers, American Staffordshire terriers, German shepherd dogs, and English springer spaniels may have increased risk for severe CPV enteritis
• In utero CPV infection is rarely associated with cerebellar hypoplasia in dogs
• Maternal antibody interference can cause vaccination failures
• Viral myocarditis is rarely noted in CPV-2 due to protective effect of maternal antibodies (and widespread vaccination), though natural disease still does occur

PATHOGENESIS:

• Parvoviral replication occurs in the nucleus and depends on host-cell DNA polymerases produced in the S phase of the cell cycle; therefore, it has a predilection for fetal, hematopoietic, lymphoid tissues, and intestinal crypt epithelium
• Host ranges of virus determined in part due to differences in capsid protein binding to the transferrin receptor for viral entry (FPV also utilizes neuraminic acid receptor)
• Oronasal exposure to contaminated feces > viral uptake by epithelium overlying tonsils and Peyer's patches > replication in nasopharyngeal lymphoid tissue (1-2 days) > dissemination in lymphoblasts to many tissues (3-4 days) > lymphocytolysis > release of virus > viremia > neutralizing antibody appears in circulation, terminating viremia (5-7 days) > myocarditis in puppies infected early in life (cardiac rhabdomyocytes are actively dividing cells in dogs under 15 days old), or infection of gastrointestinal crypt epithelium and Peyer’s patches in older puppies
• Myocardial cells are still dividing up to 15 days postnatally and are susceptible/permissive to viral infection and subsequent replication

TYPICAL CLINICAL FINDINGS:

• Three distinct syndromes:
  • Cardiac form: Rare form in puppies 3-8 weeks old; can cause sudden death (without preceding clinical signs) from cardiac arrhythmia; survivors usually die by 5 months of age from chronic myocardial fibrosis and resultant cardiac arrhythmias
  • Generalized neonatal disease: Rare form in neonatal puppies <2 weeks old; death usually occurs by 10 days of age
  • Leukopenia/enteritis: Common, often fatal form in puppies 8 weeks or older
    • Vomiting/anorexia, pyrexia, dehydration, lethargy, bloody diarrhea
    • Leukopenia, with relative or absolute lymphopenia, hypoproteinemia, and anemia
• Myocardial and enteric forms rarely occur together

TYPICAL GROSS FINDINGS:

• Cardiac form:
  • Heart: Flaccid, dilated, with myocardial pallor (diffuse or streaked) 
  • Acute congestive heart failure: Pulmonary edema, hepatic congestion, ascites, and hydrothorax
• Leukopenia/enteritis:
  • Segmental to diffuse hemorrhagic enteritis with Peyer’s patch necrosis
  • Thymic atrophy; semiliquid, yellowish bone marrow

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Cardiac form:
  • Multifocal myocardial necrosis and degeneration with intranuclear basophilic inclusion bodies in cardiomyocytes
  • Nonsuppurative (lymphocytic) to granulomatous myocarditis, +/- mineralization, fibrosis with chronicity
• Leukopenia/enteritis:
  • Severe necrohemorrhagic gastroenteritis, crypt necrosis, villous blunting and fusion
  • Lymphoid and bone marrow depletion
  • +/- multisystemic necrotizing vasculitis
  • +/- basophilic intranuclear inclusion bodies in the heart, kidney, liver, lung, gut or vascular endothelium 

ULTRASTRUCTURAL FINDINGS:

ADDITIONAL DIAGNOSTIC TESTS:

• Fecal ELISA antigen tests, fecal PCR, in situ hybridization, serology, and EM
• IFA, PCR, or IHC on the dorsal surface of the tongue, pharynx, esophagus, small intestinal mucosa, bone marrow, heart, or spleen

DIFFERENTIAL DIAGNOSIS:

• Myocardial necrosis in puppies:
  • Canine distemper virus (Paramyxoviridae, morbillivirus): Often purely degenerative; intracytoplasmic and intranuclear inclusion bodies
  • Canine herpes virus: Inflammatory exudate; intranuclear inclusions

COMPARATIVE PATHOLOGY:

Other parvoviruses of veterinary importance:

• Minute virus of canines (CPV-1): Sporadic cause of respiratory disease, mild enteritis, or myocarditis in 1-3 week old pups; enterocyte hyperplasia with intranuclear inclusions in villus epithelium, no crypt lesions 
• Feline parvovirus (feline panleukopenia): In utero infection results in cerebellar hypoplasia; panleukopenia and enteritis in postnatal kittens and cats
• There is a tentative association between feline parvovirus infection and myocarditis 
• Porcine parvovirus: Subclinical in adults; important cause of reproductive failure and the SMEDI syndrome (Stillborn, mummification, embryonic death, infertility)
• Rodent parvoviruses - Most cause subclinical infections:
  • Rats: 4 serotypes: Kilham's rat virus (rat virus), Toolan’s H1 virus, rat parvovirus, rat minute virus; rat virus is the most pathogenic and may be the only strain to cause clinical disease under natural conditions
    • Lesions in adult rats - Lymph node congestion, scrotal/ testicular/ epididymal and cerebral/ cerebellar hemorrhages, focal hepatocellular necrosis; intranuclear inclusions within hepatocytes, endothelium, biliary epithelium
    • Lesions in infant rats - Cerebellar hypoplasia, hepatitis, jaundice
  • Mice: 
    • Minute virus of mice (infant mice) - Cerebellar hypoplasia
    • Mouse parvovirus (adult mice) - Tropism for T lymphocytes resulting in immune modulation
  • Hamster parvovirus - Epizootic occurrence in weanling/suckling hamsters, high mortality; dental malformations; domed calvaria; testicular and cerebellar hypoplasia, hemorrhage 
• Mink parvoviruses:
  • Mink enteritis virus: Closely related to feline parvovirus; panleukopenia, enteritis
  • Aleutian Mink Disease (AMD): 
    • In mink, results in rapidly life-threatening immune-mediated glomerulonephritis, vasculitis, and hypergammaglobulinemia
    • In ferrets AMD is a more protracted disease (2 years or more) characterized by hypergammaglobulinemia and immune complex glomerulonephritis; prominent plasmacytic infiltrates in numerous organs especially renal interstitium, hepatic portal areas, and splenic red pulp where a nearly pure population of plasma cells expands the red pulp
• Duck parvovirus: Muscovy ducklings; hepatitis, myocarditis; closely related to adeno-associated virus 2
• Goose parvovirus: Lethal disease of young goslings and Muscovy ducks; hepatitis, myocarditis; inclusion bodies in liver, spleen, myocardium, thymus, thyroid gland, intestines
• Chicken parvovirus: Runting-stunting syndrome (RSS); impaired growth, poor feathering, mustard yellow diarrhea, osteoporosis 
• Turkey parvovirus: Poult enteritis and mortality syndrome (PEMS); similar to chickens with listlessness, depression, and splayed legs

 

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4^th ed. Ames, IA: Blackwell Publishing; 2016:17-19, 122-124, 175-176.
2. Ford J, McEndaffer L, Renshaw R, et al. Parvovirus Infection Is Associated With Myocarditis and Myocardial Fibrosis in Young Dogs. Vet Pathol. 2017:54(6):964-971.
3.    Palya VJ. Parvovirus infections of waterfowl. In: Swayne DE, Boulianne M, Logue CM, et al eds. Disease of Poultry 14th ed. Hoboken, NJ; John Wiley & Sons, Inc. 2020:474-48
4. Gal A, Castillo-Alcala F. Cardiovascular System, Pericardial Cavity, and Lymphatic Vessels. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:691-692.
5. Kim DY, Zinn MM, Odemuyiwa SO, Mitchell WJ Jr, Johnson GC. Myocarditis caused by naturally acquired canine distemper virus infection in 4 dogs. J Vet Diagn Invest. 2021;33(1):167-169.
6. Parrish CR, Sykes JE. Canine parvovirus infections and other viral enteritides. In: Sykes JE, ed. Greene’s Infectious Diseases of the Dog and Cat. 5^th ed. St. Louis, MO: Elsevier; 2023: 341-351.
7. Robinson WF, Robinson NA. Cardiovascular System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St Louis, MO: Elsevier; 2016:34.
8. Stanton J, Zachary J. Mechanisms of Microbial Infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:262-263.
9. 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.

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