JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

October 2023

P-V27

 

Signalment (JPC #3170669): Tissue from a horse.

 

HISTORY: No history provided.  

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Within multifocal to regionally extensive compressive nodules affecting approximating 40% of the section, alveolar septa are diffusely and moderately thickened up to 8x normal by loose to mature collagen, hypertrophied fibroblasts, few neutrophils, rare macrophages, and scattered congested capillaries, and are often lined by cuboidal epithelial cells (type II pneumocyte hyperplasia). The alveolar and bronchiolar lumina within these areas of fibrosis contain mild to moderate amounts of exudate characterized by few viable to necrotic neutrophils, alveolar macrophages, rare sloughed epithelial cells, eosinophilic fibrillar material (fibrin), increased clear space (edema), and hemorrhage. Rarely, alveolar macrophages contain a single 4-6 µm, eosinophilic or basophilic, intranuclear viral inclusion body that peripheralizes the chromatin and is surrounded by a thin, clear halo. Bronchialar epithelial cells are mildly hyperplastic (up to three cells thick). Diffusely the pleural and subpleural connective tissues are mildly expanded by collagen, fibroblasts, edema, few neutrophils, lymphocytes, plasma cells, and rare macrophages. The perivascular and peribronchiolar connective tissue is infiltrated by low numbers of macrophages and lymphocytes. 

 

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, interstitial, nodular and fibrosing, chronic, multifocal, moderate, with type II pneumocyte hyperplasia and rare intrahistiocytic intranuclear viral inclusions.

 

ETIOLOGY: Equid herpesvirus-5

 

DISEASE NAME: Equine multinodular pulmonary fibrosis (EMPF)

 

GENERAL DISCUSSION:

 

PATHOGENESIS:  

 

TYPICAL CLINICAL FINDINGS:  

• Low-grade fever, weight loss, progressive exercise intolerance 
• Neutrophilia and hyperfibrinogenemia 

 

TYPICAL GROSS FINDINGS:  

• Vary from individual discrete, well demarcated, fibrotic, firm tan nodules separated by normal lung parenchyma to coalescent foci with little unaffected lung 
• Tracheobronchial lymph nodes often markedly enlarged

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Distinguishing histologic features include:

• Multifocal interstitial nodules composed of mature collagen
• Preservation of “alveolar-like” architecture: Thickened alveolar septa with alveolar lumina lined by cuboidal type II pneumocytes and intraluminal neutrophils and macrophages
• Alveolar macrophages occasionally have a large, eosinophilic intranuclear inclusion body

• Mixed interstitial inflammation of predominately lymphocytes with fewer macrophages, neutrophils, and rare eosinophils

 

ADDITIONAL DIAGNOSTIC TESTS:  

• Virus isolation, PCR
• Thoracic radiographs: Interstitial to nodular pulmonary pattern
• Thoracic ultrasound: Multiple round hypoechoic masses 

 

DIFFERENTIAL DIAGNOSIS:  

• For EMPF: Pulmonary neoplasia, fungal or bacterial pneumonia, interstitial pneumonia, idiopathic pulmonary fibrosis, and pyrrolidine alkaloid toxicosis
• For interstitial fibrosis: Silicate pneumoconiosis, idiopathic granulomatous pneumonia, idiopathic pulmonary fibrosis, equine rhinopneumonitis virus (EHV4), and any disease process with chronic alveolar damage 

 

COMPARATIVE PATHOLOGY:  

• Horses: 

• EHV-5 has also been associated (case report) with erythema multiforme; skin lesions were non-pruritic, multifocal, and pustular around the eyes, nostrils and muzzle; histologically, there was interface dermatitis with keratinocyte apoptosis and intranuclear inclusions.
• One report (Carrillo et al, JDVI 2020) of an organizing pneumonia characterized by multifocal areas of alveolar thickening with fibromyxoid connective tissue with no etiology found (not associated with EHV-5)

• Pulmonary fibrosis in other species:  

• Donkey pulmonary fibrosis: A common finding in the lung of aged donkeys; multifocal to coalescing visceral pleural/subpleural (intra-alveolar) fibrosis over dorsal lung; cause unknown (no link to gammaherpesvirus AHV-4 or AHV-5)

• AHV-4 and AHV-5 causes interstitial pneumonia in donkeys with bronchiolitis, type II pneumocyte hyperplasia, and presence of syncytial cells but not inclusion bodies; may also cause interstitial fibrosis

• West Highland White Terrier dogs: Deposition of collagenous matrix in septa and around small blood vessels;  no infectious cause has been identified  
• Idiopathic pulmonary fibrosis in cats:  patchy, multinodular areas where alveoli are thickened by smooth muscle, fibrosis, fibroblasts and myofibroblasts; cause is unknown but inappropriate apoptosis of type II pneumocytes may be involved 

 

REFERENCES: 

1. Carrillo MF, Kemper D, Woods LW, et al. Chronic interstitial pneumonia with features of organizing pneumonia in an adult horse. J Vet Diagn Invest. 2020;32(4):621-625. 
2. 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 Limited; 2016:514-515; 568-569.
3. Lopez A, Martinson SA.  Respiratory system, thoracic cavities, mediastinum, and pleurae.   In:  Zachary JF, ed. Pathologic Basis of Veterinary Disease, 6^th ed. St Louis, MO: Elsevier; 2022: 604.
4. Mauldin AE, Peters-Kennedy J.  Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol. 1. 6th ed. St. Louis, MO: Elsevier Limited; 2016:627.
5. Ochi A, Sekiguchi M Tsujimura K, et al. Two cases of equine multinodular pulmonary fibrosis in Japan. J Comp Pathol. 2019:170:46-52.

Click the slide to view.

---