JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2023

P-M05 (NP)

 

Signalment (JPC #2017918): Two-year-old, American quarter horse, gelding.

 

HISTORY: The horse presented to veterinarian with a five-day history of dyspnea.

 

HISTOPATHOLOGIC DESCRIPTION: Lung: There are multifocal to coalescing patchy areas of consolidation throughout the section. Approximately 50% of alveolar spaces and to a lesser extent bronchioles are filled with a cellular exudate composed of predominately foamy macrophages that often contain discrete, variably sized clear vacuoles (lipid) that peripheralize the nucleus. The exudate is also composed of numerous viable and necrotic neutrophils, fewer lymphocytes and plasma cells, occasional erythrocytes (hemorrhage), sloughed epithelial cells, and rare multinucleated foreign body-type giant cells admixed with abundant eosinophilic, homogeneous to fibrillar material (edema and fibrin), extracellular lipid globules, and small amounts of necrotic debris. Alveolar septa are either occasionally discontinuous with loss and necrosis of type I pneumocytes (septal necrosis); lined by plump, cuboidal type II pneumocytes (type II pneumocyte hyperplasia); mineralized; or often thickened 2-4 times normal by fibrin, edema, increased macrophages, lymphocytes, and minimal fibrosis. Multifocally, bronchiolar epithelium is mildly attenuated or hyperplastic. The pleura and interlobular septa are expanded 2‑4 times normal by congested blood vessels, edema, fibrin, the previously described inflammatory cells, and fibrosis.  

 

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, fibronecrotizing, subacute, multifocal, moderate, with intrahistiocytic and extracellular lipid globules, type II pneumocyte hyperplasia, fibrin, hemorrhage, and edema, American quarter horse, equine.    

 

CONDITION: Exogenous lipid pneumonia (mineral oil)

 

SYNONYMS: Cholesterol pneumonia; lipoid pneumonia; paraffinoma

 

GENERAL DISCUSSION:  

• Lipid pneumonia, type of noninfectious irritant or aspiration of foreign material

• Classified as exogenous or endogenous based on the source of lipid

• Exogenous lipid pneumonia may result from either aspiration of oily substances or gastroesophageal reflux
• In horses and cattle, often due to inappropriate administration of mineral oil for the treatment of gastrointestinal disorders, or in cats in an attempt to remove hairballs (aspiration pneumonia). 
• Always consider in animals whose swallowing has been compromised (aspiration) 
• Neurological diseases such as encephalitis (e.g. rabies) or encephalopathy (e.g. lead poisoning) should be investigated in cases where aspiration pneumonia is not explained otherwise

 

PATHOGENESIS:  

• Aspiration may result from faulty administration of the material or from depressed swallowing reflexes
• Chemically inert oils: Mineral oil is not hydrolyzed > small amounts are expectorated or removed through the lymphatics > residual mineral oil produces a chronic granulomatous, fibrotic response
• Vegetable oils: Emulsified > removed by expectoration > little or no tissue reaction
• Animal origin oils: Hydrolyzed by lipases > liberated free fatty acids > severe acute inflammatory response (exudation of serofibrinous fluid and leukocytes with replacement by foamy macrophages and giant cells) > thickening of alveolar septa by mononuclear cells and fibrosis

 

TYPICAL CLINICAL FINDINGS: 

• Subclinical to severe dyspnea
• Clinical, pathologic, and radiographic findings are non‑specific

 

TYPICAL GROSS FINDINGS: 

• Involvement is usually the right cranial lung lobe, but distribution can vary 
• Lesions uncomplicated by secondary bacterial infection have a yellowish, homogenous, or finely mottled appearance
• Variable: Multiple small pale nodules; sharply defined areas; or complete consolidation of a lobe

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Foamy, lipid‑laden macrophages fill alveoli
• Alveolar walls are thickened by infiltrating mononuclear cells, fibrosis, prominent type II pneumocyte hyperplasia, and occasional giant cells
• In exogenous lipid pneumonia, lipid is both intracellular and extracellular 

 

ADDITIONAL DIAGNOSTIC TESTS: 

• Mineral oil will not stain with osmic acid
• Lipid may be demonstrated with oil red O or Sudan black on frozen sections
• Cytologic findings:
  1. Variably sized, colorless, round structures (lipid) and discrete, colorless, cytoplasmic vacuoles (phagocytosed lipid) within macrophages
  2. Fewer lymphocytes and neutrophils
  3. May see multinucleate giant cells, epithelioid macrophages (granulomatous inflammation)

 

DIFFERENTIAL DIAGNOSIS:

• Endogenous lipid pneumonia: Most common in laboratory rodents (may be associated with drug induced alveolar phospholipidosis), cats, ferrets, and dogs; 
  • Clinical signs include dyspnea, cough, and mucus expectoration, or asymptomatic
  • Subpleural alveoli filled with foamy macrophages with intracellular lipid presumed to be surfactant and degenerative cell membrane; cholesterol clefts and multinucleated giant cells
  • More extreme end of the spectrum from alveolar histiocytosis 
  • Gross appearance is irregular sub-pleural, yellow-white, firm foci that are sharply defined and/or bulge
  • Chronic bronchitis, bronchogenic carcinoma, and Dirofilaria immitis have been coexistent in cats and dogs
  • Documented in blue-fronted Amazon parrot (Amazona aestiva) with atherosclerosis; foamy macrophages filled parabronchi (Grespan, J Comp Pathol. 2023)
• Differentials for lipid pneumonia: Mycobacterial infections, Morbillivirus (Canine Distemper Virus) in Arctic foxes (Stimmelmayr, J Vet Diagn Invest. 2018)
• Differentials for foamy macrophages:  Pneumocystis sp., Histoplasma sp., Leishmania sp., or environmental mycobacterial infections
• Pulmonary hyalinosis (P-M04): Incidental finding in older dogs; accumulations of macrophages and giant cells containing laminated or amphophilic hyaline PAS positive material 
• Other agents commonly aspirated include barium and kaolin (P-M03)

 

COMPARATIVE PATHOLOGY:

• Exogenous lipid pneumonia reported in dogs, cats, cattle, horses, and humans
  1. Occurs in cats when treated with oral mineral oil in attempt to remove hairballs
• Endogenous lipid pneumonia common in mice, ferrets, raccoons, and opossums; less common in dogs, cats, laboratory rats, llamas, and parrots
  1. In North American opossums:
     • Multifocal yellow white subpleural plaques
     • Aggregates of foamy macrophages in alveolar walls and spaces, minimal disruption of pulmonary architecture
     • More severe cases form large nodular lesions
     • Associated with Didelphostrongylus hayesi (bronchiolar obstruction)
• Alveolar proteinosis in mice: Progressive accumulation of granular pale eosinophilic phospholipid (surfactant) with low numbers of macrophages; PAS positive material and diastase resistant; ultrastructural, consists of lamellar, tubular myelin-like arrays

 

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4^th  ed. Ames, IA: Iowa State Press; 2016:100.
2. Beaufrere H, et al. Lipid-related lesions in quaker parrots (Myiopsitta monachus). Vet Pathol:2019; 56(2): 282-288. 
3. Boes KM. Respiratory System. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023:215. 
4. Caswell JL, Williams KJ . The respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals, Vol 2, 6th ed. St. Louis, MO: Elsevier; 2016: 517.
5. Costa T, el al. Endogenous lipid pneumonia in an African grey parrot (Psittacus erithacus erithacus). J Comp Pathol. 2013; 149(2-3): 381-384.
6. Grespan A, Fiedler RT, Guedini BT, Costa LD, Raso TF. Endogenous lipid pneumonia associated with atherosclerosis in a blue-fronted Amazon parrot (Amazona aestiva). J Comp Pathol. 2023;201:130-134.
7. Grimes CN, Fry MM, LeBlanc CJ, Hecht S. The Lung and Intrathoracic Structures. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2020:272. 
8. Higgins D, Rose K, Spratt D. Monotremes and Marsupials. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:457. 
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; 2022:571-572; 606.
10. Raya AI, et al. Endogenous lipid pneumonia in a dog. J Comp Pathol. 2006; 135(2-3):153-155.
11. Schmidt R, Reavill DR, Phalen DN. Pathology of Pet and Aviary Birds. 2nd ed. Ames, IA: John Wiley & Sons, Inc.; 2015:43. 
12. Stimmelmayr, R, et al. Morbillivirus-associated lipid pneumonia in Arctic foxes. J Vet Diag Invest. 2018; 30(6): 933-936. 

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