JPC SYSTEMIC PATHOLOGY
PULMONARY SYSTEM
October 2023
P-V13
Signalment (JPC #1619887): Three-week-old pig, breed and gender unspecified
HISTORY: This pig died after developing upper respiratory distress. At necropsy, there was a fibrinonecrotic membrane lining the nasal sinuses
HISTOPATHOLOGIC DESCRIPTION: Nasal turbinate: Diffusely, the submucosa is thickened up to 1 mm by many infiltrating lymphocytes, plasma cells, and fewer macrophages which infiltrate to the level of the turbinate bones multifocally. The respiratory epithelium is diffusely either ulcerated, attenuated, or has undergone multifocal squamous metaplasia, and there are small amounts of fibrin and hemorrhage adhered to the mucosa. Nasal mucus gland epithelial cells are often enlarged up to 50 µm in diameter (cytomegaly) with abundant, often vacuolated cytoplasm and a single 20-30µm, basophilic, irregular, smudgy to granular intranuclear viral inclusion that fills and distends the karyomegalic nucleus. Multifocally, the mucus glands are ectatic, often lined by attenuated, degenerate, or necrotic epithelium, and gland lumina often contain an exudate composed of viable and degenerate neutrophils admixed with variable amounts of amphophilic mucus and necrotic cellular debris. The nasal cavity is partially filled with an exudate composed of hemorrhage and sloughed and necrotic epithelial cells. Multifocally, the vascular endothelium is hypertrophic (reactive), and perivascular connective tissue is edematous with dilated lymphatics. There are multifocal areas of mild turbinate bone resorption and remodeling.
MORPHOLOGIC DIAGNOSIS: Nasal turbinate: Rhinitis, necrotizing and lymphoplasmacytic, subacute, diffuse, marked, with mucosal ulceration and mucus gland epithelial karyomegaly, cytomegaly, and intranuclear viral inclusions, breed unspecified, porcine.
ETIOLOGIC DIAGNOSIS: Cytomegaloviral rhinitis
CAUSE: Suid Herpesvirus 2 (porcine cytomegalovirus)
CONDITION: Inclusion body rhinitis
GENERAL DISSCUSION:
- Betaherpesvirus that causes an acute to subacute, mild rhinitis with high morbidity and low mortality 3-5-week-old suckling piglets
- Secondary bacterial infections will increase mortality rate
- Systemic infections usually affect piglets <3 weeks of age
- Betaherpesviruses have a limited host range and they produce cytomegaly and karyomegaly with prominent basophilic intranuclear inclusion bodies
PATHOGENESIS:
- Pathogenesis incompletely understood; damage caused by virus may be secondary to injury of epithelial cells and immune response – worsened by secondary bacterial infection
- Unclear how virus gets through mucus layer to epithelial cell site of action and how exactly it spreads systemically (though monocyte system/trafficking seems to play a role)
- Virus shed in nasal and ocular secretions,
- Virus is inhaled or enters conjunctiva with movement down lacrimal duct à replication in nasal/sinus epithelium à dysfunction and lysis of epithelial cells à lymphocytic and necrotizing rhinitis à viremia à monocyte trafficking to epithelial cells à necrosis
- Inclusions are most numerous in epithelium but also occur in macrophages and endothelial cells
- The mild rhinitis can progress to a mucopurulent discharge with subsequent blockage of nasal passages and interference with suckling, resulting in rapid weight loss and death (or poor growth/weight gain)
TYPICAL CLINICAL FINDINGS:
- Piglets:
- Mild, transient rhinitis with fever, sneezing, mucoid nasal discharge, and epiphora
- Systemic disease: sudden death, or sneezing, anorexia, lethargy, subcutaneous edema of the jaw and tarsal joints, and dyspnea
- Naïve pregnant sows: Mild lethargy and anorexia with delivery of stillborn or weak piglets
TYPICAL GROSS FINDINGS:
- Uncomplicated cases in suckling piglets (3-5 weeks): Usually none to hyperemic nasal mucosa
- Mucopurulent nasal exudate present with secondary bacterial infection
- Systemic disease in neonates (<3 weeks): Catarrhal rhinitis, hydrothorax, hydropericardium, pulmonary and subcutaneous edema, and renal petechiae
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Inclusion bodies, cytomegaly, and karyomegaly are pathognomonic when present
- Necrotizing, nonsuppurative rhinitis with large, 8-12 um, basophilic, intranuclear viral inclusion bodies in epithelial cells of nasal mucosa and cytomegaly of the nasal epithelium, mucosal glands and ducts, and Harderian and lacrimal glands
- Lymphocytic infiltration in lamina propria
- Macrophages and lymphocytes accumulate in glands
- Squamous metaplasia of nasal epithelium
- Systemic infection:
- Intranuclear viral inclusions in epithelial cells of renal tubules and glomeruli; lacrimal, Harderian and salivary glands; glial cells in CNS (focal gliosis)
- Less commonly in hepatocytes, adrenal gland, esophageal submucosal glands, lymph nodes, spleen, lung, macrophages, and endothelial cells
ULTRASTRUCTURAL FINDINGS:
- dsDNA virus with an enveloped virion approximately 150-200 nm in diameter and an 80-120 nm diameter, icosahedral nucleocapsid
ADDITIONAL DIAGNOSTICS:
- Virus isolation, immunofluorescence, or PCR on nasal scrapings, lung wash cells, or kidney homogenates
DIFFERENTIAL DIAGNOSIS:
- Atrophic rhinitis, a mixed bacterial (Pasteurella multocida and Bordetella bronchiseptica) infection that results in inflammation and atrophy of the nasal turbinates with septal deviation
- Penetrating wounds or removal of needle teeth can introduce Fusobacterium necrophorum, causing a paranasal abscess in young pigs (bull nose)
- Adenovirus: Intranuclear inclusions (but not cytomegaly); typically found in GI
- Pseudorabies: Also has intranuclear inclusions (less obvious) and can be found in respiratory tract, but brain is more common – inclusions are eosinophilic however
COMPARATIVE PATHOLOGY:
- Selected other Betaherpesviruses
- NHPs – Simian cytomegaloviruses affect both OWM & NWM
- Disease occurs in SIV or SRV infected macaques
- Mice – Murid herpesvirus 1 and 2 (mouse CMV)
- Rats – Murid herpesvirus 8 (rat CMV)
- Guinea Pigs – Caviid herpesvirus 2 (D-V12, guinea pig CMV)
- All lab rodent species commonly have salivary gland as tissue affected
- Elephants – Elephant endotheliotropic herpesvirus, NOT a cytomegalovirus (EEHV)
References:
- Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:529-530, 537.
- Cheville NF, Lehmkuhl H. Cytopathology of Viral Diseases. In: Ultrastructural Pathology: The Comparative Cellular Basis of Disease. 2nd ed. Ames, IA: Wiley-Blackwell; 2009: 335, 338.
- Matz-Rensing K et al. New World and Old World Monkeys. In: Terio KA et al., eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 350-351.
- Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. Ames, IA: John Wiley & Sons, Inc.; 2016: 15-16,122,219.
- Landolfi JA, Terrell SP. Proboscidae. In: Terio KA et al, eds. Pathology of Wildlife and Zoo Animals. 1st ed. San Diego, CA: Elsevier, Inc; 2018:419-423.
- Lowenstine LJ, et al. Apes. In: Terio KA et al., eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 384-385.
- Lopez A, Martinson SA. Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022: 624
- Mettenleiter TC, Ehlers B, Muller T, Yoon KJ, Tiefke JP. Herpesviruses. In: Zimmerman JJ et al, eds. Diseases of Swine. 11th ed. Hoboken, NJ: Wiley; 2019: 561-565.
- Stanton JB, Zachary JF. Mechanisms of Microbial Infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022: 256.