JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2023

P-M02 (NP)

 

Signalment (JPC #1914189): Dog, age and breed unspecified

 

HISTORY: Died shortly after induction of anesthesia

 

HISTOPATHOLOGIC DESCRIPTION: Affecting approximately 70% of the terminal bronchioles and to a lesser extent small bronchioles, extending from the bronchiolar epithelium and partially to completely occluding the bronchiolar lumina are dense polyps of fibro-collagenous tissue, lined by cuboidal to attenuated epithelium. Polyps are composed of fibroblasts, collagen, and rare foamy macrophages. Affected bronchioles are surrounded by few lymphocytes, macrophages, and rare plasma cells. Alveolar septa near affected terminal bronchioles are slightly thickened up to three times normal by previously described inflammatory cells and mild type II pneumocyte hyperplasia. Smooth muscle surrounding affected bronchioles is moderately hyperplastic. There is increased clear space (edema) within the tunic adventitia of vessels within pulmonary interstitium. There is increased clear space (edema) within the pleural interstitium, and mesothelial cells are mildly hypertrophic (reactive).

 

MORPHOLOGIC DIAGNOSIS: Lung: Bronchiolar fibrous polyps, chronic, multifocal, moderate (bronchiolitis obliterans), breed unspecified, canine.

 

CONDITION: Bronchiolitis obliterans

 

SYNONYMS: Bronchiolitis fibrosa obliterans, obliterative bronchiolitis, organizing bronchiolitis; historically referred to as bronchiolitis obliterans organizing pneumonia (BOOP) or cryptogenic organizing pneumonia (COP)

 

GENERAL DISCUSSION:

• Bronchiolitis obliterans (BO) is a sequel to chronic bronchiolar damage which can be induced by any agent that severely damages bronchiolar epithelium 
  1. Described as wound healing gone awry
• BO used to describe the presence of fibrous polyps occluding the bronchiolar lumen
  1. BO is occasionally used elsewhere to describe acute lesions in which intraluminal aggregates of neutrophils obstruct airflow
• BO is a distinct entity different from constrictive bronchiolitis and hyaline scars (which involves the airway wall)
• Commonly identified within lesions of chronic bronchopneumonia in cattleà viral or neutrophil-mediated epithelial damage

 

PATHOGENESIS:

• The most common sequelae of fibrinous bronchopneumonia include alveolar fibrosis (organizing pneumonia) and bronchiolitis obliterans
• Damage to bronchiolar epithelium from many different causes (ranging from viral, inflammation, toxins, lung worms, etc.) à Fibrinous exudate in bronchiolar lumina à Organization and attachment (Fibroblast infiltration & neovascularization of the exudate) à Proliferation and migration of epithelial cells over the surface à Fibrous polyps à Luminal obstruction à Reduced air flow & gas exchange
• May occur in as little as 7-10 days following bronchiolar epithelial damage
• Polyps cause restriction of airflow and inhibit alveolar ventilation
• Pathogenesis of right heart failure that may develop in calves with history of viral pulmonary infection: Lungs may appear normal grossly, but on histology may show most bronchioles are occluded by epithelium covered polyps (bronchiolitis obliterans) à alveolar hypoventilation à pulmonary vascular constriction à pulmonary hypertension and medial hypertrophy of pulmonary arterioles à cor pulmonale with right heart failure 

 

TYPICAL CLINICAL FINDINGS:  

 

TYPICAL GROSS FINDINGS:  

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Polypoid proliferative projections from bronchiolar lumina composed of fibrous connective tissue admixed with inflammatory cells with partial to complete occlusion of bronchioles
• Polyps often covered by ciliated epithelial cells
• Medial hypertrophy of pulmonary arteries may be present 

 

ADDITIONAL DIAGNOSTIC TESTS:

 

DIFFERENTIAL DIAGNOSIS:

• Constrictive bronchiolitis: Not normally seen in animals
  1. Seen in human medicine (especially in lung transplants) à Fibrosis of the bronchiolar wall causes external compression à Reducing lumen diameter
• Hyaline Scars: Seen in lambs; nodular masses of fibrillar eosinophilic matrix and fibroblasts within wall of bronchioles (not intraluminal as in BO) à Compress the lumen à Do not form intrabronchiolar polyps (no epithelial lining); Usually caused by chronic viral or mycoplasmal pneumonia

 

COMPARATIVE PATHOLOGY:

• Bronchiolitis obliterans occurs in multiple species, including
  1. Apes secondary to a variety of viral infections, including influenza virus pneumonia
  2. Mice and rats following Sendai virus infection
  3. Humans and experimentally in rats following chronic inhalation of food flavorings (such as microwave popcorn butter flavoring) (Hubbs et al, Toxicol Pathol. 2019)
• Similar lesions to BO have been described in avian species following chronic exposure to smoke with damage to secondary and tertiary bronchi

 

 

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell; 2016: 
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; 2007:504-505.
3. Lowenstine LJ, McManamon R, Terio KA. Apes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:389. 
4. Lowenstein LJ, Osborn KG. Strait K, Else JG, Eberhard ML. Respiratory System Diseases of Nonhuman Primates. In: Abee CR, Mansfield K, Tardif S, Morris T. Nonhuman Primates in Biomedical Research: Volume 2: Diseases. 2^nd ed. San Diego, CA: Elsevier; 2012: 444.
5. 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; 2022:553-54, 587, 617.
6. Schmidt R, Reavill DR, Phalen DN. Respiratory System. In: Pathology of Pet and Aviary Birds. 2nd ed. Ames, IA: John Wiley & Sons, Inc.; 2015:42.
7. Hubbs AF, Kreiss K, et al. Flavorings-Related Lung Disease: A Brief Review and New Mechanistic Data. Toxicol Pathol. 2019 Dec;47(8):1012-1026.

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