JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
October 2018
D-V05

Signalment (JPC# 1902055):  Sprague-Dawley rat

HISTORY:  Swellings of the anteroventral cervical area were noted in 3 Sprague-Dawley rats in a colony of 20 rats.

HISTOPATHOLOGY DESCRIPTION:  Salivary gland, submandibular and parotid:  Approximately 80 percent of the salivary adenomeres exhibit one of the following changes: shrunken acini with loss of central acinar lumina (atrophy); acini lined by swollen epithelial cells with vacuolated, lightly basophilic cytoplasm that are occasionally distended up to 20um by a large clear vacuole (degeneration); acinar cells with condensed, hypereosinophilic cytoplasm with pyknotic nuclei (necrosis); or acini are lost and replaced with fibrin, edema, mild hemorrhage and moderate numbers of neutrophils, fewer lymphocytes, plasma cells and macrophages.  Ducts are often lined by flattened epithelial cells (squamous metaplasia), are up to 5 cells thick with increased mitotic figures (ductular regeneration), or are occasionally lined by necrotic epithelial cells which slough into the lumen, and multifocally contain eosinophilic and karryorhectic cellular debris (necrosis).  Diffusely, the interstitium, interlobular septa, and periglandular tissue are expanded up to three times normal by edema, fibrin and hemorrhage admixed with previously described inflammatory cells, and blood vessels are often lined by reactive endothelium.  The parotid (serous) salivary gland is similarly but less severely affected.

Lymph node, mandibular:  There are large coalescing lymphoid follicles with prominent germinal centers that contain many tingible body macrophages.  The paracortex and medulla are mildly expanded by increased lymphocytes and low to moderate numbers of macrophages.  Blood vessels are mildly congested and there is moderate intranodal and perinodal hemorrhage.

MORPHOLOGIC DIAGNOSIS:

1. Salivary glands, submandibular and parotid: Sialoadenitis, necrotizing, subacute, diffuse, moderate, with ductular squamous metaplasia and regeneration, Sprague-Dawley rat, rodent.
2. Lymph node, mandibular: Lymphoid hyperplasia, diffuse, mild, with draining hemorrhage.

ETIOLOGIC DIAGNOSIS:  Coronaviral sialoadenitis

CAUSE: Rat coronavirus (Rat sialodacryoadenitis virus - SDAV)

GENERAL DISCUSSION:

• SDAV includes any coronavirus isolate that causes necrosis of salivary and lacrimal glands; virulence varies between strains
• Coronaviruses are enveloped, single-stranded RNA viruses
• Causes transient necrotizing lesions affecting the parotid, submaxillary salivary glands, Harderian gland, exorbital glands and other lacrimal glands, lacrimal duct, nasal cavity; may produce respiratory disease in young rats (rhinitis, tracheitis, pneumonia)
• Mucous salivary glands (sublingual) are not affected
• Athymic nude rats are particularly susceptible and develop chronic persistent infections and wasting disease
• Significant additive effects in rats previously exposed to Mycoplasma pulmonis and CAR bacillus

PATHOGENESIS:

• Transmitted by infected nasal secretions and saliva
• Rapid spread in susceptible populations; high morbidity, low mortality
• Often subclinical
• Two stages:
  • Acute stage: Virus infects epithelial cells, causing necrosis of ductular structures spreading to adjacent acini and effacement of normal architecture
  • Reparative stage: Nonkeratinizing squamous metaplasia of ductal and acinar structures of salivary and lacrimal glands takes place with reactive hyperplasia of cervical lymph nodes
• Decreases salivary gland production of epidermal growth factor (EGF), affecting carcinogenicity studies and possibly reproduction
  • Damage to olfactory epithelium and epithelium within the vomeronasal organ may affect pheromone detection and therefore reproduction

TYPICAL CLINICAL FINDINGS:

• Cervical or intermandibular swelling, sniffling, blepharospasm, keratoconjunctivitis (lack of tear production), epiphora, and nasal and lacrimal discharges
• Chromodacryorrhea: Porphyrin-containing red encrustations around eyes and nares (characteristic pink fluorescence under ultraviolet light); NOT specific for rat coronavirus
• Reproductive problems: Irregular cycling, small litters, neonatal mortality

TYPICAL GROSS FINDINGS:

• Swelling of the submaxillary and parotid salivary glands with interlobular and periglandular edema
• Regional lymph node enlargement
• Unilateral or bilateral glaucoma/megaloglobus, hyphema and corneal ulceration
• Chromodacryorrhea
• Rhinitis

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Acute stage: 

• Coagulative necrosis of salivary and lacrimal ductal structures with disrupted architecture
• Edema admixed with mixed inflammatory cell infiltrate and fibrin
• Respiratory epithelium: Loss of cilia and mucosal necrosis; edema, inflammation, goblet cell loss, fibrinocellular exudates; epithelial hyperplasia (tracheitis, focal bronchitis and bronchiolitis)
  • Necrotizing rhinitis with mixed inflammatory infiltrate
• Ophthalmic lesions: Keratitis, keratoconjunctivitis; occasionally anterior uveitis and glaucoma with multifocal retinal degeneration Reparative stage:
• Nonkeratinizing squamous metaplasia of ductal and acinar structures, and Harderian glands with mixed inflammation; reactive hyperplasia of cervical lymph nodes 7-10 days post-exposure

ULTRASTRUCTURE:

• Virions are spherical, 60-70 nm, with a rim of petal-shaped peplomers
• Found in cytolysosomes of epithelial cells, in dilated tubules in the smooth ER, and free in the lumen

ADDITIONAL DIAGNOSTIC TESTS:

• Serologic testing with IFA and ELISA
• PCR

DIFFERENTIAL DIAGNOSIS:

• Viral infections of salivary glands
  • Cytomegalovirus (betaherpesvirus): Infects salivary and lacrimal glands; ductal cytomegaly with intranuclear and intracytoplasmic inclusions; nonsuppurative inflammation; common in wild mice, not laboratory mice
  • Papovavirus (Polyomavirus): Pneumonia and parotid sialoadenitis; intranuclear inclusions in the ducts, occasionally in acini
• Nasal and ocular discharge
  • Sendai virus (Paramyxovirus): More often affects the lower respiratory tract than does SDAV; suppurative to necrotizing bronchitis, alveolitis
  • Pneumonia virus of mice (Paramyxovirus): Multifocal, nonsuppurative vasculitis and interstitial pneumonia; also affects hamsters, rats, less often guinea pigs and gerbils
  • Mycoplasma pulmonis: Suppurative rhinitis with polymorphonuclear and lymphocytic infiltration and hyperplasia of submucosal glands
• Ocular and nasal irritation in rats: Elevated ammonia levels; stress
• Edema of tissues associated with the head: Psuedomonas aeruginosa
• Squamous metaplasia: Vitamin A deficiency; lacks inflammation and necrosis

COMPARATIVE PATHOLOGY:

• Group 1 coronaviruses:
  • Canine coronavirus type 1 & 2 (CoV)
  • Canine coronavirus CB/05
  • Feline coronavirus type 1 & 2 (FCoV)
  • Transmissible gastroenteritis virus (TGEV) of swine
  • Porcine respiratory coronavirus (PRCoV)
  • Porcine epidemic diarrhea virus (PEDV)
  • Human coronavirus 229E and NL63
  • Ferret coronavirus (epizootic catarrhal enteritis)
• Group 2 coronaviruses:
  • Group 2A (bovine-like)
    • Bovine coronavirus (BCoV)
    • Mouse hepatitis virus (MHV)
    • Rat coronavirus
    • Porcine haemagglutinating encephalomyelitis virus (PHEV)
    • Human coronavirus OC43
    • Human enteric coronavirus
    • Equine coronavirus
    • Canine respiratory coronavirus
  • Group 2B (SARS-like)
    • Severe acute respiratory syndrome coronavirus
    • Bat and wild carnivore isolates
  • Group 3 coronaviruses:
    • Avian bronchitis
    • Turkey coronavirus

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:27, 125-127.
2. Bihun CGD, Percy DH. Morphologic changes in the nasal cavity associated with sialodacryoadenitis virus infection in the Wistar rat. Vet Pathol.  1995;32:1-10.
3. Boorman GA, Eustis SL. Lung. In: Boorman GA, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds. Pathology of the Fischer Rat. San Diego, CA: Academic Press; 1990:348-349.
4. Liang SC, Schoeb TR, Davis JK, Simecka JW, Cassell GH, Lindsey JR. Comparative severity of respiratory lesions of sialodacryoadenitis virus and sendai virus infections in Lewis and F344 rats. Vet Pathol. 1995;32:661-667.
5. Macy JD, Weir EC, Barthold SW. Reproductive abnormalities associated with a coronavirus infection in rats. Lab An Sc. 1996;46:129-132.
6. Neuenschwander SB, Elwell MR. Salivary glands. In: Boorman GA, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds. Pathology of the Fischer Rat. San Diego, CA: Academic Press; 1990:35-36.
7. Williams DL. Laboratory animal ophthalmology. In: Gelatt KN, ed. Veterinary Ophthalmology. 3rd ed. Philadelphia, PA: Lippincott, Williams, Wilkins; 1999:1214-1215.
8. Holmberg BJ. Ophthalmology of exotic pets.  In: Maggs DJ, Miller, PE, Ofri R, eds.  Slatter’s Fundamentals of Veterinary Ophthalmology. 4th ed. St. Louis, MO: Elsevier; 2008:433-434.

Click the slide to view.

---