JPC SYSTEMIC PATHOLOGY

HISTOPATHOLOGIC DESCRIPTION

Lung: Expanding approximately 75% of alveolar septa and peribronchial and perivascular interstitium and compressing adjacent alveoli are multifocal to coalescing granulomas centered on abundant epithelioid macrophages that contain intracytoplasmic, amphophilic to light brown, granular to spicular, anisotropic material. This material is also present extracellularly. Surrounding the core of macrophages are rare multinucleated giant cells (Langhans type) further surrounded by a rim of lymphocytes, plasma cells, and fewer neutrophils. In less severely affected areas, alveolar lumina are filled with eosinophilic homogenous proteinaceous material (edema) and scattered macrophages. There is multifocal minimal type II pneumocyte hyperplasia.

GENERAL

• Pneumoconiosis less common in animals than humans due to lack of occupational exposure (most common inorganic dusts inhaled are carbon, asbestos, or silica)
• Anthracosis: deposition of carbon (e.g. from cigarette smoke or polluted air)
• Asbestosis: characterized by ferruginous asbestos bodies (linear, beaded fibers with globose ends); animals do not have asbestos-associated mesothelioma

PATHOGENESIS

• Macrophages engulf dust induces fibrosis and granulomatous inflammation
• Some materials (especially silica) elicit inflammation via TNF-α, IL-1, and IL-6 promoting fibrosis
• Iron contamination may increase silicate toxicity by increasing hydroxyl radicals, oxidative damage, disruption of macrophage lysosomal membranes

TYPICAL CLINICAL FINDINGS

• Silicosis: equine chronic interstitial pneumonia, weight loss, exercise intolerance, dyspnea, osteoporosis-like bone fragility
• Anthracosis and asbestosis common findings in dogs, with unknown clinical significance
• Incidental in most captive birds

TYPICAL GROSS FINDINGS

• Silicate inhalation: miliary gritty lesions throughout lung
• Anthracosis: fine gray-black stippling on lung, discoloration of tracheobronchial lymph nodes
• Dust granulomas in birds usually not grossly evident, but can be large with necrotic centers

TYPICAL LIGHT MICROSCOPIC FINDINGS

• Lesions centered on bronchioles, less frequently in interlobular septa
• Multifocal fibrosis and granulomatous inflammation
• Can have necrosis and mineralization
• Silica: birefringent crystals within macrophage cytoplasm (can be clear, brown, black)
• Anthracosis: fine black granular and crystalline material in macrophages
• Dust granuloma (birds): can have dense aggregates of brown pigment and nodular organization of histiocytes; most often in parabronchi walls, occasionally in secondary bronchi; do NOT elicit fibrosis

ADDITIONAL DIAGNOSTIC TESTS

• Silicate crystals can be highlighted by acid-fast stains and X-ray spectroscopy
• Dust particles are variably birefringent with polarized light
• Scanning electron microscopy

DIFFERENTIAL DIAGNOSES

• Aspiration pneumonia: generally due to liquids in animals
  • Due to force feeding, nasogastric tubes passed into lungs, vomiting/regurgitation, recumbency, anesthesia, cleft palate
  • Bronchopneumonia with unilateral, asymmetrical lesions
  • If anaerobic bacteria involved there is necrosis, foul smell, liquefaction

Foreign material in lungs:

• Barium Sulfate: In peracute cases, anisotropic crystals of barium sulfate may be free within airways without any noticeable cellular response; in older lesions, material may be within neutrophils or macrophages surrounded by areas of fibrosis
• Siderosis: Iron dust is inhaled primarily as hematite or iron oxide and does not incite fibrosis or an inflammatory reaction; hematite and iron oxide appear as red crystals of varying size; they are anisotropic, appear orange with polarized light, and can be demonstrated with iron stains such as Prussian blue
• Kaolin: a hydrated silicate previously used in many antidiarrhea medications; when aspirated it causes interstitial pneumonia, neck and thoracic cavity granulomas
• Asbestosis: Asbestos bodies are long beaded rods with rounded ends, which appear yellow due to an iron coating, which can be demonstrated with a Prussian blue stain; incites fibrous scarring of the pleura, around bronchioles and alveolar ducts, and within alveolar septa; discrete nodules, as in silicosis, do not develop
• Anthracosilicosis: Macrophages near terminal bronchiolar areas contain black, granular isotropic carbon pigment inter-mixed with numerous anisotropic crystalline spicules (silicate crystals)
• Lipid pneumonia/mineral oil: Most commonly seen in cats where mineral oil is used as a laxative to relieve chronic constipation or in horses after treatment of impaction colic with mineral oil via nasogastric tube
• Asian sand dust (kosa aerosol): Causes air pollution in China, Korea and Japan; granulomas that are composed of epithelioid cells, macrophages, multinucleated giant cells, neutrophils and crystal-like transparent particles
• Meconium: Most common in neonatal calves, lungs contain amorphous yellow-orange meconium, keratin, and squamous epithelial cells; obstructs airways hypoxic pulmonary vasoconstriction pulmonary hypertension and right-to-left shunting across ductus arteriosus or foramen ovale

COMPARATIVE PATHOLOGY

• Captive kiwi: marked lesions associated with dry, dusty substrates and bird’s sniffing behavior during feeding and substrate investigation
• Avian species: species differences in susceptibility with woodpeckers, granivorous, and burrowing birds being more tolerant than arboreal birds exposed to smoke
• NHP: chronic progressive process may not be clinically apparent until granulomatous inflammation and fibrosis extends to adjacent parenchyma
• Rock hyraxes multifocal to coalescing macrophages and fibrous tissue with silica crystals suspected due to play sand housing
• Humans: grading system exists for assessment of silicotic/asbestos nodules and has been utilized for statistical analysis of animals (Walker et al 2023)
• Mongoose: high prevalence of silicate accumulations hypothesized due to small size, dry habitat and burrowing behaviors
• Leopards: common insignificant finding attributed to increased inhalation during dry season, with increase in environmental exposure

REFERENCES

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