JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2026

P-V27

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. Bronchiolar 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.

GENERAL DISCUSSION

• Equine multinodular pulmonary fibrosis (EMPF) is a progressive, fibrosing interstitial lung disease in adult horses associated with Equid herpesvirus-5, a gammaherpesvirus (enveloped, dsDNA)

PATHOGENESIS

• Poorly understood, however, virus has been detected with PCR and virus isolation within EMPF lesions and EMPF has been induced in horses inoculated with EHV-5

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 with erythema interface dermatitis (Peters-Kennedy et al, 2023); skin lesions were non-pruritic, multifocal, crusted, irregular to annular areas over the face, nostrils, and muzzle; EHV-5 was confirmed via qPCR and ISH in 7 horses and by EM in 1 horse.
• Recent case report of interstitial pneumonia in two foals with EHV-5 confirmed on PCR and ISH along with histologic findings consistent with EMPF in the absence of any other infectious causes poses the question of EHV-5’s potential role in neonatal pneumonia in foals.
• 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. Caswell JL, Williams KJ. Respiratory System. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 2. 7th ed. Elsevier; 2026: 563-564.
2. Lopez A, Martinson SA. Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. Elsevier; 2022:604.
3. Mauldin EA, Welle MM. Integumentary System. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 1. 7th ed. Elsevier; 2026:636.
4. Peters-Kennedy J, Lohr CV, Cossic B, Glaser AL, Duhamel GE. Association of equine gammaherpesvirus-5 with facial lymphohistiocytic interface dermatitis in seven adult horses from the United States. Vet Pathol. 2023; 60(6):888-897.
5. Ochi A, Takechi M, Fujii S, Ohno O, Kishi D, Ueno T. Interstitial pneumonia associated with equid gammaherpesvirus 5 infection in 2 neonatal foals, and a retrospective study in Hokkaido, Japan. J Vet Diagn Invest. 2026; 38(4):792-799.