JPC SYSTEMIC PATHOLOGY

SPECIAL SENSES SYSTEM

April 2024

S-V02

Signalment (JPC #2015685): Rat

HISTORY: This rat was one of six in a group of 28 rats that spontaneously developed ocular lesions. Grossly, the corners of both eyes were opaque and dry; the right eye had central ulceration and hyphema and the associated Harderian gland was slightly darker than normal.

HISTOPATHOLOGIC DESCRIPTION: 1. Harderian gland: Diffusely, acini are atrophied, decreased in number, and multifocally infiltrated by macrophages, fewer lymphocytes and plasma cells, and rare neutrophils. Remaining acini are lined by cells that pile up to 3 cell layers thick, have a high nuclear to cytoplasmic ratio, large vesiculate nuclei, and frequent mitotic figures (regeneration). Intralobular and interlobular ducts are prominent (secondary to decreased acinar parenchyma), ectatic, and multifocally lined by hyperplastic or flattened cells (squamous metaplasia), and occasionally contain sloughed cells and necrotic debris. Multifocally, macrophages contain small amounts of intracytoplasic yellowish-brown, finely granular material (porphyrin). The gland stroma is mildly edematous.

2. Eye: Diffusely, the corneal stroma and to a lesser extent the conjunctiva and sclera are expanded by a severe neutrophilic and lymphoplasmacytic infiltrate (keratitis, conjunctivitis, scleritis), blood vessels (corneal vascularization), and increased clear space and irregular corneal stromal clefting (corneal edema). The corneal epithelium is focally ulcerated and replaced by a serocellular crust. The corneal epithelium adjacent to the ulcer is hyperplastic and keratinized, exhibits intracellular edema, and there are transmigrating neutrophils and lymphocytes. The conjunctival epithelium is mildly to moderately hyperplastic with occasional transmigrating inflammatory cells. The anterior and posterior chambers and vitreous compartment are filled with abundant hemorrhage which surrounds the lens, fibrin, and proteinaceous fluid admixed with few hemosiderin-laden macrophages, neutrophils, lymphocytes, and plasma cells. A fibrovascular membrane extends across the vitreous chamber, encircles the lens, and extends to the ciliary body (intravitreal and cyclitic fibrovascular membranes). Multifocally, the iris epithelium is adhered to Descemet’s membrane (anterior synechia). The filtration angle is obscured by hypertrophied fibroblasts, hemorrhage, fibrin, few macrophages, and viable and degenerate neutrophils. Lens epithelial cells are hypertrophied with microvacuolated cytoplasm, and extend around the lens an increased distance posterior to the equator (mild posterior migration of lens epithelium). Diffusely there is liquefaction of lenticular fibers with replacement by eosinophilic, globular material (Morgagnian globules). The retina artifactual detachment of the retina.

MORPHOLOGIC DIAGNOSIS: 1. Harderian gland: Adenitis, lymphohistiocytic, chronic, diffuse, severe, with acinar atrophy and regeneration, ductal ectasia, and squamous metaplasia, rat, rodent.

2. Eye: Keratitis, ulcerative, neutrophilic and histiocytic, diffuse, severe, with corneal keratinization, anterior uveitis, hemophthalmos, conjunctivitis, anterior synechia, and cataractous change.

ETIOLOGIC DIAGNOSIS: Coronaviral dacryoadenitis

CAUSE: Sialodacryoadenitis virus (SDAV)

GENERAL DISCUSSION:

SDAV is a morphological term and represents any and all coronavirus isolates that results in necrotizing inflammation of the salivary and lacrimal glands
Single stranded RNA coronavirus
Targets lacrimal and salivary glands as well as the respiratory tract
Self-limiting, acute disease in all ages of rats
Sporadic outbreaks occur in laboratory and pet rats; may be enzootic in some research colonies and in pet and free-ranging rats
Subclinical to high morbidity; low mortality, except through anesthetic deaths
Potential to compromise toxicological studies
Affects serous glands (parotid, submandibular, Harderian)
Does not affect mucous glands (sublingual)

PATHOGENESIS:

Transmission by nasal secretions or saliva
Infects and replicates in upper respiratory tract > spreads to salivary and lacrimal glands > secondary lesions in the nasopharynx, respiratory tract, and eyes by an unknown mechanism
Ocular lesions are secondary to lacrimal gland dysfunction
Neonatal rats often develop pneumonia and olfactory dysfunction leading to nursing failure and death
Reproductive disorders such as neonatal death and alteration in the estrous cycle have been associated with SDAV
Athymic nude rats develop chronic persistent infections and wasting disease

TYPICAL CLINICAL FINDINGS:

Range from subclinical infections to explosive, enzootic outbreaks
Intermandibular swelling; enlarged submandibular and parotid salivary glands
Excessive lacrimation, red ocular and nasal discharge or encrustations, photophobia, sneezing, sniffling, epiphora, blepharospasm, keratoconjunctivitis, cataracts
Red encrustations around eyes and nares contain porphyrins, which exhibit bright pink fluorescence under UV light
Secondary ocular changes: Unilateral or bilateral corneal ulcers, hyphema, glaucoma

TYPICAL GROSS FINDINGS:

Parotid and submandibular salivary glands, Harderian glands, extraorbital glands, and cervical lymph nodes are enlarged, pale, and edematous
Blotchy, brown pigmentation of Harderian glands due to the accumulation of porphyrin within the acini
Enlarged and edematous cervical lymph nodes

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Acute stage: Acute necrotizing adenitis; characterized by necrotizing inflammation (neutrophilic and monocytic) of salivary and lacrimal glands (coagulation necrosis of ductal structures with variable involvement of adjacent acini and effacement of normal architecture)
Reparative stage (>7 days postinfection): Nonkeratinizing squamous metaplasia most marked in Harderian glands of ductal and acinar structures, monocytic inflammation; reactive hyperplasia of cervical lymph nodes; fibrosis
Rhinitis, tracheitis, bronchitis, and bronchiolitis in severe and chronic cases
Mucous salivary glands (sublingual) not affected
Mononuclear to neutrophilic rhinitis, tracheitis, bronchitis or bronchiolitis with occasional respiratory epithelial hyperplasia, loss of cilia and epithelial flattening

ULTRASTRUCTURAL FINDINGS:

Pleomorphic, 60‑200 nm diameter virion
Envelope covered by 20 nm long club‑shaped radial surface projections (peplomers)

ADDITIONAL DIAGNOSTIC TESTS:

Typical microscopic lesions in salivary and lacrimal glands are diagnostic
Serology (IFA, ELISA)
Viral antigen in respiratory tract and affected glands 4-6 days post-exposure
SDAV is distinguished from rat coronavirus by cell culture

DIFFERENTIAL DIAGNOSIS:

Dacryoadenitis in rats:

Necrotizing inflammation of the Harderian gland may occur following orbital puncture for blood sampling (lesion is more localized than SDAV)
Autoimmune dacryoadenitis causes a granulomatous reaction

Other coronaviruses in rats:

    Parkers rat coronavirus (PRC): Primarily lung lesions with only minimal salivary or lacrimal involvement

COMPARATIVE PATHOLOGY:

Mice can be experimentally infected and develop multifocal interstitial pneumonia; natural infection does not occur
Coronaviruses in other species generally do not cause similar lesions

REFERENCES:

Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: John Wiley & Sons; 2016:125-127.
Delaney MA, Treuting PM, Rothenburger JL. Rodentia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 508.