JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2023

P-M01

 

Signalment (JPC #2285063): 8-year-old female German shepherd dog

 

HISTORY: This dog had a productive cough and progressive weight loss. Radiographic examination revealed consolidation of the right middle, caudal and accessory lung lobes.

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Approximately 60% of the section is effaced and replaced by multifocal to coalescing eosinophilic granulomas that compress adjacent less affected pulmonary parenchyma. Eosinophilic granulomas are centered on a core of hypereosinophilic cellular and karyorrhectic debris (lytic necrosis) admixed with numerous degenerate eosinophils and fewer degenerate neutrophils. Eosinophils often surround irregular bands or radiating spicules of brightly eosinophilic, hyalinized collagen (flame figures). Necrotic foci are surrounded by epithelioid macrophages, eosinophils, lymphocytes, and plasma cells, and are further surrounded by a thick rim of fibroblasts and abundant collagen (fibrosis). Eosinophilic granulomas are separated by compressed pulmonary parenchyma with architecture obscured by numerous alveolar macrophages, eosinophils, lymphocytes, and plasma cells admixed with moderate amounts of fibrin and edema, and scant cellular and karyorrhectic debris, that also forms an exudate that fills adjacent alveoli. Adjacent alveolar septa are thickened up to 4x normal by abundant fibrosis and low numbers of macrophages and lymphocytes with few plasma cells and eosinophils, and are occasionally lined by cuboidal pneumocytes (type II pneumocyte hyperplasia). Multifocally, the peribronchiolar and perivascular interstitia are expanded up to 5 times normal by dense fibrous connective tissue (fibrosis) and low numbers of previously described inflammatory cells. There is multifocal bronchiolar smooth muscle hypertrophy. Less affected alveoli contain increased numbers of foamy alveolar macrophages, and remaining bronchioles are often lined by hyperplastic epithelium and contain the previously described inflammatory exudate. The pleura is diffusely thickened up to 1 mm in some areas by fibrosis, ectatic lymphatic vessels (edema), and low numbers of previously described inflammatory cells.

 

MORPHOLOGIC DIAGNOSIS: Lung: Eosinophilic granulomas, multifocal to coalescing, severe, with flame figures, marked fibrosis, and bronchiolar smooth muscle hypertrophy, German shepherd dog, canine.

 

CONDITION: Eosinophilic pulmonary granulomatosis (EPG) 

 

SYNONYMS: Pulmonary infiltrates with eosinophils, pulmonary eosinophilia (PE), eosinophilic pneumonia, and pulmonary hypersensitivity

 

GENERAL DISCUSSION:

• Eosinophilic bronchopneumopathy (EBP) is an uncommon, usually steroid- responsive condition of young dogs
• No breed or sex predilection, generally dogs <3 years old; may be the most common cause of bronchiectasis in dogs 
• Diagnosis of exclusion; the process is thought to be immune mediated, but following should be excluded:
  • Tracheobronchial parasites: Crenosoma vulpis, Eucoleus aerophilus, Oslerus osleri
  • Lungworms: Angiostrongylus vasorum, Filaroides hirthi, occult Dirofilaria immitis
  • Neoplasia: Pulmonary carcinoma, histiocytic sarcoma, lymphoma
  • Aspergillosis 
  • Drug reaction
• Eosinophilic pulmonary granulomatosis (EPG) may be a severe form of EBP which tends to form distinct nodules or mass-like pulmonary lesions (as in this case); has a poorer prognosis
  • May represent a progressive form of EBP  
  • Generally a much higher and more consistent peripheral eosinophilia (>20,000/mL)
  • Like in EBP, some (but not all) have occult dirofilariasis

 

PATHOGENESIS:

• In both humans and dogs, hypersensitivity to airborne allergens is the suspected (but not confirmed) cause of EBP: 
  • Inciting allergen rarely identified
  • Suspected causes: Fungi, molds, drugs, bacteria, parasites
  • Dirofilariasis has been associated with EBP and EPG in dogs

 

TYPICAL CLINICAL FINDINGS:  

• Highly variable: Often include productive, corticosteroid-responsive cough; gagging; retching; exercise intolerance, dyspnea, and green nasal discharge; bronchoconstriction typically not a major feature
• Bronchoscopy: Green mucus, collapsed airways with nodular changes

 

TYPICAL GROSS FINDINGS: 

• Lung lobes may be firm, consolidated, and fail to collapse 
• EPG: Multifocal to regionally extensive, greenish-tan, discrete, nodules
  • Extrapulmonary nodules may also be found in the intrathoracic lymph nodes (hilar lymphadenopathy may be severe), liver, spleen, abdominal lymph nodes, small intestine, and kidneys
  • Adult heartworms may be present

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Highly variable, owing to diverse clinical picture and likely variety of causes
• Acute: Alveoli flooded with eosinophils, lymphocytes, and histiocytes;
• Subacute: Type II pneumocyte hyperplasia, epithelial ulceration, microhemorrhage
• Chronic: Chronic eosinophilic bronchitis with epithelial hyperplasia, ulceration, or squamous metaplasia; bronchiectasis in 25% of cases
• Lung parenchyma: Diffuse eosinophilic and granulomatous infiltrates, focal eosinophilic granuloma centered on necrotic tissue and densely eosinophilic material and large areas of necrosis and fibrosis
• Perivascular infiltration with lymphocytes and eosinophils is inconsistent
• EPG:
  • Interstitial pneumonia with granulomas that obliterate normal architecture
  • Granulomas contain dense aggregates of epithelioid macrophages, eosinophils, fewer plasma cells, lymphocytes, and mast cells with occasional areas of necrosis
  • Bronchial smooth muscle hypertrophy prominent in granulomatous areas
  • Possible infiltration of eosinophils or eosinophilic granulomas throughout the body (e.g., intrathoracic lymph nodes, liver, spleen, trachea, peripheral or abdominal lymph nodes, small intestine and kidney)

 

ADDITIONAL DIAGNOSTIC TESTS:  

• CBC and differential: Eosinophilia and basophilia are the most common abnormalities; however, eosinophilia may be absent in spite of marked pulmonary involvement; variable neutrophilia
• Cytology: TTW/BAL fluid, and thoracic aspirates may have increased cell counts (cells/uL) with elevated percentages of eosinophils and neutrophils
• Rule out other causes of eosinophilic pulmonary disease:
  • Heartworm tests – microfilaria-concentrating and antigen tests
  • Fecal samples (multiple) – fecal flotation and Baermann examination to check for lungworm infection
  • Serology for endemic mycotic diseases

 

DIFFERENTIAL DIAGNOSIS: 

• Differential diagnosis for eosinophilic lung disease:
  • Hypersensitivity - pulmonary parasites, D. immitis, drugs, or aeroallergens 
  • Infection – parasitic, fungal, bacteria
• Gross differential diagnosis for pulmonary nodules +/- hilar lymphadenopathy:
  • Systemic mycoses
  • Primary and metastatic pulmonary neoplasia
  • Lymphoid granulomatosis

 

COMPARATIVE PATHOLOGY:  

• Brown Norway rats – Eosinophilic granulomatous pneumonia:
  • Model for studying asthma pathogenesis
  • May develop spontaneous eosinophil-rich granulomatous pneumonia in absence of experimental procedure
  • Gross: Multifocal tan to gray 1-3 mm foci throughout lungs
  • Histologic: Multifocal to diffuse granulomatous pneumonitis with a cellular infiltrate of epithelioid cells with occasional multinucleated giant cells
• One case of fatal eosinophilic bronchitis has been reported in a rhesus macaque; no gross lesions, but histology revealed bronchioles filled with mucus, sloughed epithelium, and macrophages, and bronchial walls heavily infiltrated by mixed inflammatory cells in which eosinophils predominated.

 

REFERENCES:

1. Abbott DEE, Allen AL. Canine eosinophilic pulmonary granulomatosis: case report and literature review. J Vet Diagn Invest. 2020;32(2):329-335.
2. Abee CR, Mansfield K, Tardif S, Morris T. Nonhuman Primates in Biomedical Research: Volume 2: Diseases. 2^nd ed. San Diego, CA: Elsevier; 2012:438.
3. Caswell JL, Williams KJ. Respiratory system.  In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, PA:Elsevier Saunders; 2016: 501-502, 513.
4. 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; 2020:273. 
5. Johnson LR, Johnson EG, Hulsebosch SE, Dear JD, Vernau W. Eosinophilic bronchitis, eosinophilic granuloma, and eosinophilic bronchopneumopathy in 75 dogs (2006-2016). J Vet Intern Med. 2019;33(5):2217-2226.
6. Percy DH, Barthold SW, Griffey SM. Pathology of laboratory rodents and rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:160.

 

 

 

 

 

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