JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2026 P-M05 (NP)

HISTOPATHOLOGIC DESCRIPTION:

Lung: There are multifocal to coalescing patchy areas of consolidation throughout the section. Approximately 40% 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 lysed and intact 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 2-4x 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 2‑4x normal by congested blood vessels, edema, fibrin, the previously described inflammatory cells, and fibrosis.

GENERAL DISCUSSION:

• Lipid pneumonia, type of noninfectious irritant or aspiration of foreign material
• Classified as exogenous or endogenous based on the source of lipid
• Condition is part of alveolar filling disorders; material accumulates in alveoli secondary to impeded clearance
• Exogenous lipid pneumonia may result from either aspiration of oily substances or gastroesophageal reflux
  • Aspiration pneumonia secondary to aspiration of droplets of oil; oils of animal origin are high irritant
• Horses and cattle: Often due to inappropriate administration of mineral oil for the treatment of gastrointestinal disorders
• Cats: Due to an attempt to remove hairballs (aspiration pneumonia)

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
  • Non‑specific: Dyspnea, coughing, mucus expectoration

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:

• Cytologic findings:
  • Variably sized, colorless, round structures (lipid) and discrete, colorless, cytoplasmic vacuoles (phagocytosed lipid) within macrophages
  • Fewer lymphocytes and neutrophils
  • May see multinucleate giant cells, epithelioid macrophages (granulomatous inflammation)
  • Must be differentiated from endogenous lipid pneumonia
• Foamy, lipid‑laden macrophages fill alveoli and accumulate in peribronchial and interlobar septal lymphatics
• Alveolar walls are thickened by infiltrating mononuclear cells, fibrosis, prominent type II pneumocyte hyperplasia, and occasional giant cells
  • +/- epithelioid macrophages
• In exogenous lipid pneumonia, lipid is both intracellular and extracellular
• Extracellular lipid globules appear as clear spherical spaces with distinct borders

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
• Diagnostic imaging: radiography, CT
• Lung aspiration
• Sputum examination
• Bronchioalveolar lavage

DIFFERENTIAL DIAGNOSIS:

• Endogenous lipid pneumonia: Most common in laboratory rodents and mustelids and cats
  • More extreme end of the spectrum from alveolar histiocytosis
    • Dogs more reported with only alveolar histiocytosis
  • Mostly idiopathic; can be secondary to airway obstruction (exudates, bronchoconstriction, tumors, anomalous bronchi), reduced airway clearance, or increased exudate
    • Lipid accumulated most is surfactant or lipid from degenerated cells
  • May be associated with drug induced alveolar phospholipidosis or mutations in surfactant protein D
    • Lipid accumulates within macrophage lysosomes (alveolar foam cells)
  • May be secondary to bronchiectasis
    • Pigs, sheep, goats, cats, and dogs, with bronchial and bronchiolar obstruction due to parasitic bronchitis
    • Chronic bronchitis or bronchiectasis can lead to bronchiectasis
    • In cats left lung lobe most affected; in dogs right cranial lung lobe affected
  • Associated with cancerous lung lesions in cats, dogs, and humans
  • Often subclinical in cats and dogs
  • Gross appearance is irregular sub-pleural, yellow-white, firm foci that are sharply defined and/or bulge that rarely exceed 1 cm in diameter
  • Histology features
    • Alveolar histiocytosis: multifocal subpleural alveolar histiocytosis
    • Endogenous lipid pneumonia: Macrophages contain intracytoplasmic lipid, +/- cholesterol crystals; severe cases may not see lipid, intracellular and extracellular cholesterol crystals present with severe interstitial fibrosis, type II pneumocyte proliferation, giant cell accumulation, intra-alveolar fibroplasia, and accumulation of neutrophils and mononuclear inflammatory cells
  • Documented in blue-fronted Amazon parrot (Amazona aestiva) with atherosclerosis; foamy macrophages filled parabronchi (Grespan, J Comp Pathol. 2023)
  • Humans: Secondary to lipid storage disease and injury to type II pneumocytes (particulates and irritant gases)
• 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:

• Endogenous lipid pneumonia
  • North American opossums:
    • Incidental; multifocal plaques on dorsocaudal pleura
    • Aggregates of foamy macrophages in alveolar walls and spaces, minimal disruption of pulmonary architecture; severe cases form large nodules
    • Associated with Didelphostrongylus hayesi (bronchiolar obstruction)
    • A report associated with papillary adenocarcinoma (Falconier, 2025)
  • Companion birds
    • Parabronchi filled with proteinaceous fluid and foam cells
    • Air capillary collapse
    • Epithelial metaplasia, pneumocyte hyperplasia, smooth muscle hypertrophy, fibrosis, +/- adipose cell proliferation within lobules
  • A case in jungle cat reported (Kang, 2024)
• 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

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