JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2017

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 alveoli spaces and to a lesser extent bronchioles are filled with a cellular exudate composed predominately foamy macrophages that often contain discrete, variably sized clear vacuoles (lipid) that peripheralize the nucleus.  The exudate also contains numerous viable and degenerate neutrophils, fewer lymphocytes and plasma cells, occasional erythrocytes (hemorrhage), sloughed epithelial cells, and rare multinucleated foreign body giant cells admixed with abundant eosinophilic, homogeneous to fibrillar material (edema and fibrin) extracellular lipid globules, and small amounts of necrotic debris.  There is necrosis and loss of type I pneumocytes and alveolar septa are thickened by fibrin, edema, increased macrophages and lymphocytes.  Multifocally there is type II pneumocyte hyperplasia and foci of mineralization involving alveolar septa.  Multifocally, bronchiolar epithelium is mildly attenuated or hyperplastic.  The pleura, interlobular septa, and 80% of the alveolar septa are expanded 2‑4 times normal by congested blood vessels, edema, fibrin, the previously described inflammatory cells, and fibrosis. 

MORPHOLOGIC DIAGNOSIS:  Lung:  Pneumonia, fibrinous and necrotizing, 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
• Basis off 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
• Causes of endogenous lipid pneumonia (EnLP) are often unknown
  • Occurs when pulmonary cell membranes degenerate causing release of cholesterol and other lipids into the alveolar spaces
  • Associated with bronchial obstruction, disturbance of lipid metabolism, lipids from pulmonary surfactant, or from degenerated cells

 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
• Endogenous lipid pneumonia: See below under differential diagnosis

TYPICAL CLINICAL FINDINGS:

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

TYPICAL GROSS FINDINGS:

• Involvement is usually bilateral and ventral
• 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

DIFFERENTIAL DIAGNOSIS:

• Endogenous lipid pneumonia: Most common in laboratory rodents (may be associated with drug induced alveolar phospholipidosis), cats, ferrets, and dogs;
  • 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
• Differentials for foamy macrophages: Pneumocystis , Histoplasma sp., Leishmania sp., or environmental mycobacterial infections
• Pulmonary hyalinosis: 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

COMPARATIVE PATHOLOGY:

• Exogenous lipid pneumonia reported in dogs, cats, cattle, horses, and humans
  • 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 and llamas
• 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, et al. Pathology of Laboratory Rodents and Rabbits. 4^th Ames, IA: Iowa State Press; 2016:100.
2. Bolo E, et al. Endogenous lipid (cholesterol) pneumonia in three captive Siberian tigers (Panthera tigris altaica). J Vet Diag Invest. 2012; 24:618-620.
3. Caswell JL, et al. 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.
4. Costa T, el al. Endogenous lipid pneumonia in an African grey parrot (Psittacus erithacus erithacus). J Comp Pathol. 2013; 149(2-3): 381-384.
5. Lopez A, et al. Respiratory system, mediastinum and pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6^th St. Louis, MO: Mosby Elsevier; 2016: 505, 528.
6. Perpinan D, et al. Pulmonary adenocarcinoma and endogenous lipid pneumonia in a common genet (Genetta genetta). J Zoo Wildl Med. 2010; 41(4): 710-712.
7. Raya AI, et al. Endogenous lipid pneumonia in a dog. J Comp Pathol. 2006;135(2-3):153-155.

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