JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
November 2021
D-V12 (NP)
Signalment (JPC #1171326): A guinea pig
HISTORY: Incidental finding
HISTOPATHOLOGIC DESCRIPTION: Salivary gland: Multifocally within periductal areas the interstitium is expanded by moderate numbers of lymphocytes and fewer plasma cells and macrophages, admixed with small amounts of necrotic cellular and karyorrhectic debris. Multifocally, rare acinar cells are enlarged up to ten times normal (cytomegaly), with abundant eosinophilic granular cytoplasm and one to two nuclei containing an 8-12 um diameter, deeply eosinophilic, round to oval intranuclear inclusion body which marginates the chromatin (“owl eye cells”). Multifocally, there is deeply basophilic mineral.
MORPHOLOGIC DIAGNOSIS: Salivary gland: Sialoadenitis, lymphoplasmacytic, multifocal, mild, with rare acinar cytomegaly with eosinophilic intranuclear inclusion bodies, breed unspecified, guinea pig (Cavia porcellus), rodent.
ETIOLOGIC DIAGNOSIS: Herpesviral sialoadenitis
CAUSE: Guinea pig cytomegalovirus (GPCMV); Caviid herpesvirus 2
GENERAL DISCUSSION:
- Common incidental finding in guinea pigs, affecting up to 70-80% of adults
- Animal model for human cytomegalovirus infection
- Cytomegaloviruses belong to the family Herpesviridae, subfamily betaherpesvirus; species-specific
- dsDNA virus with fibrous core, icosahedral capsid
- Replicates in host cell nucleus; acquires envelope by budding through the host nuclear membrane; fragile, does not survive in environment
- Transmission requires close contact with infected body secretions (e.g. coitus, nursing, closely confined populations)
- Latent phase, with relapses during periods of stress
PATHOGENESIS:
- Transmission via exposure to infected saliva or urine or transplacentally
- Guinea pigs are used as an animal model because both humans and guinea pigs have hemochorial placentation with a single trophoblast layer; transplacental transmission and fetal infection occur in both species
- Maternal and fetal outcomes are dependent on many variables (timing and route of infection, strain of guinea pig, source of virus and maternal immunity); viral inoculation early in pregnancy tends to lead to pup resorption, whereas challenge in late pregnancy tends to lead to pup mortality; maternal immunity may reduce in utero transmission and improve fetal outcomes
- Salivary glands, kidney, and liver are the primary target tissues for GPCMV in the guinea pig
TYPICAL CLINICAL FINDINGS: None
TYPICAL GROSS FINDINGS: None
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Lesions are primarily to the ductal epithelial cells of the salivary glands
- Karyomegaly with large eosinophilic intranuclear inclusion bodies that marginate chromatin (“owl eye cells”)
- Lymphoplasmacytic or neutrophilic inflammation
- Interstitial pneumonitis and multifocal necrosis within lymph nodes, spleen, liver, kidney, and lung may be present in acute systemic form of the disease
DIAGNOSIS:
- Viral isolation from actively shedding animals
- Serology (ELISA)
- In situ hybridization
DIFFERENTIAL DIAGNOSIS: (For intranuclear inclusions)
- Guinea pig herpes-like virus (Caviid herpesvirus 1): Isolated from many strains of guinea pigs; no clinical signs; no gross or microscopic lesions; produces intranuclear inclusions in degenerating kidney cell cultures
- Guinea pig X virus (Caviid herpesvirus 3): Experimentally, Hartley guinea pigs develop focal hepatic necrosis and mortality; has not been shown to cause natural disease, but could be a complicating factor in laboratory animals
- Guinea pig adenovirus infection: Large basophilic intranuclear inclusions in respiratory epithelium; severe pneumonia
COMPARATIVE PATHOLOGY:
CMV in other species:
- Rodents:
- Mice (mouse CMV, uncommon in laboratory mice),
- Rats (rat CMV, common in wild rats, but nonexistent in laboratory rats)
- Chinese hamsters (Cricetid herpesvirus, CrHV-1); usually asymptomatic, inclusion body sialoadenitis; does not cross the placenta
- Swine (Suid herpesvirus-2, CMV)
- Inclusion body rhinitis: mild to severe nonsuppurative necrotizing rhinitis in suckling piglets 3-5 weeks of age; histologically, there are large 8-12um basophilic intranuclear inclusion bodies within the epithelial cells of nasal mucosal glands/ducts; may go systemic in piglets <3 weeks old, affecting the kidneys and other organs
- Porcine cytomegalovirus abortion: When pregnant sows are infected, they may deliver small litters, mummified fetuses, or stillborn or weak piglets
- Non-human primates: Common, asymptomatic, host-specific, latent infection in many species of NHP
- Macaques (macacine herpesvirus-3): most are seropositive by 6 months old; can cause disease in immunosuppressed (common with SIV or SRV), including disseminated necrotizing lesions in the brain, lymph nodes, liver, spleen, kidney, small intestine, and nervous system
- Chimpanzees: develop disseminated CMV infection in captivity; occasional intranuclear inclusions in myocardium, retina, brain, salivary gland, spleen, lymph node, stomach, tonsil, pancreas, intestine, arteries, and adrenal gland
- Bovids (bovine herpesvirus-4, BoHV-4, Movar virus): An important cause of abortion in cattle (and occasionally swine); classified as a gammaherpesvirus; also responsible for infectious bovine cervicovaginitis and epididymitis (epivag) in African bovids
- Bats: CMV has been detected in the acinar cells of the submandibular gland of two captive Myotis lucifugus; asymptomatic with cytomegaly microscopically
- Hedgehogs: CMV has been isolated from the salivary glands of asymptomatic African hedgehogs with cytomegalic inclusion disease (CID)
- Humans (human cytomegalovirus, HCMV or human herpesvirus-5, HHV5): Most frequent congenital infection worldwide; leading cause of sensorineural hearing loss, developmental delay, and neurological deficits; transplacental transmission during maternal viremia
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