JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2023

P-M03 (NP)

 

Signalment (JPC #1820691): Unknown age and gender owl monkey.

 

HISTORY: Unknown

 

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.  

 

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, granulomatous, multifocal to coalescing, severe, with intraalveolar and intrahistiocytic anisotropic foreign material, owl monkey, Aotus trivirgatus, primate.

 

ETIOLOGIC DIAGNOSIS: Inhalation/aspiration (foreign body) pneumonia

 

CAUSE: Kaolin 

 

SYNONYMS: Bolus alba, white clay, China clay, Fuller’s earth

 

GENERAL: 

• Kaolin is a hydrated aluminum silicate (kaolinite) previously used in many antidiarrheal medications
• When aspirated, it causes interstitial pneumonia and neck and anterior thoracic cavity granulomas 

 

PATHOGENESIS:  

• Initially, the alveolar epithelial and capillary endothelial cells are injured and then serofibrinous exudate fills the alveoli 
• In severe cases, hyaline membranes composed of fibrin, serum proteins, and cell debris line the air spaces
• Upon initial contact with the particles, alveolar macrophages release chemotactic factors (IL-8) that recruit activated inflammatory cells; these cells infiltrate alveolar lumina and interstitium, then release injurious (oxidants, cytokines) and fibrogenic mediators (platelet derived growth factor, fibroblast growth factor, IL-1)
• Fibroblasts proliferate and there is increased collagen deposition in the interstitium  
• If there are multiple or more severe episodes or chronic exposure, inflammation persists and normal regeneration is inhibited

 

TYPICAL CLINICAL FINDINGS:  

 

TYPICAL GROSS FINDINGS: 

• Multifocal areas of pulmonary consolidation and hyperemia; lesions are commonly lobar 
• Distribution depends on the position of the animal upon inhalation or aspiration of foreign material  
  • If standing, middle and accessory lobe bronchi of the right or left side affected  
  • If prostrate, middle, cranial or accessory lobes of the recumbent side affected 
• Kaolinite granulomas may be small, cystic, spongy masses or firm, variably sized masses; some may cavitate and contain a creamy, gray, nonodorous material

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• In acute lesions, there is peribronchial to diffuse, intraalveolar dull eosinophilic exudate containing varying numbers of macrophages and neutrophils 
• Highly birefringent, irregular, needle-shaped crystals are phagocytized by macrophages and admixed with the exudates
• With any aspiration pneumonia, there can be acute bronchiolitis with various degrees of acute alveolar inflammation and foreign material or lipids  
• Chronically, form classic granulomas

 

DIFFERENTIAL DIAGNOSES:

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
• Silicosis: Microscopically, anisotropic crystals within areas of fibrosis, which appear as dense sclerotic coalescing nodules
• 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
• 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 airwaysàhypoxic pulmonary vasoconstrictionàpulmonary hypertension and right-to-left shunting across ductus arteriosus or foramen ovale

 

COMPARATIVE PATHOLOGY:

• Pneumoconiosis: Lung disease from inhalation and retention of inorganic dusts
  • Humans: Dense pulmonary scarring or fibrosis (mining or industrial exposure)
  • Horses (and rarely dogs): Silicate pneumoconiosis (silicosis) is the only clinically important pneumoconiosis in domestic animals and occurs in certain geographical areas containing crystalline forms of free silica in the soil; in horses, associated with osteoporosis and equine bone fragility syndrome
  • Ratites: Common in captive kiwi and lesions can be marked (associated with dry, dusty substrates and enhanced by the bird’s sniffing behavior during feeding and substrate investigation):
• Aspiration pneumonia in domestic animals is often of liquids, a common sequela to cleft palate, and has the following characteristics
  • Localized or unilateral (right cranial lung lobe most severely affected unless animal in lateral recumbency)
  • Extensive necrosis, liquefaction, foul smell, rapid green discoloration
  • Plant material may be visible in herbivores
• Inhaled milk is observed in pail-fed or tube-fed calves

 

REFERENCES:

1. Arens AM, Barr B, Puchalski SM, et. al. Osteoporosis associated with pulmonary silicosis in an equine bone fragility syndrome. Vet Pathol. 2011;48(3):593-615.
2. Bischoff K. Toxicity of over-the-counter drugs. In: Gupta RC ed. Veterinary Toxicology: Basic and Clinical Principles. New York, NY: Academic Press; 2007:388.
3. Bowden DH, Adamson YR. Fibroblast interactions with alveolar and interstitial macrophages. Models: silicosis and abestosis in the mouse. In: Jones TC, Dungworth DL, Mohr U, eds. Monographs on Pathology of Laboratory Animals: Respiratory System. 2nd ed. New York, NY: Springer-Verlag;1996: 265-269. 
4. 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: Elsvier; 2016:508-509, 516-518. 
5. Haschek WM, Rousseaux CG. Handbook of Toxicologic Pathology. San Diego, CA: Academic Press; 1991:805-809. 
6. Husain AN. The lung. In: Kumar V, Abbas AK, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease. 10th ed. Philadelphia, PA: Elsevier; 2020:711.
7. Jones TC, Hunt RD, and King NW. Veterinary Pathology. 6th ed. Baltimore, MD: Williams & Wilkins; 1997:65.

8. Klaassen CD. Casarett & Doull’s Toxicology, The Basic Science of Poisons. 6th ed. New York, NY: McGraw Hill; 2001:526-529. 

9. 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; 2022:559-561.
10. Naota M, Shiotsu S, Shimada A, Kohara Y, Morita T, Inoue K, Takano H. Pathological study of chronic pulmonary toxicity induced by intratracheally instilled Asian sand dust (kosa). Tox Pathol. 2013;41:48-62.
11. Smith DA. Palaeognathae: Apterygiformes, Casuariiformes, Rheiformes, Struthioniformes; Tinamiformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals, Cambridge, MA Academic Press; 2018: 638.

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