JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

August 2023

P-B17

 

Signalment (JPC #2130811): Beagle

 

HISTORY: This dog was found dead.

 

HISTOPATHOLOGIC DESCRIPTION: Pleura (per contributor): Diffusely, the pleura is expanded up to 10mm, often forming papillary projections, and contains multifocal to coalescing variably sized foci of pyogranulomatous inflammation and areas of lytic necrosis. Foci of lytic necrosis are characterized by loss of normal architecture with replacement by necrotic cellular debris, degenerate neutrophils, fibrin, and areas of drop-out, often centered on large (up to 1.5mm) mats of 2µm, beaded, filamentous bacilli. Bacteria are admixed with large accumulations of finely granular basophilic to eosinophilic material which radiates outwards (Splendore-Hoeppli material; “sulfur granules”). Surrounding necrotic areas and markedly expanding the surrounding pleura there are numerous viable and degenerate neutrophils, epithelioid macrophages, few multinucleated giant macrophages, and aggregates of lymphocytes and plasma cells admixed with hemorrhage, fibrin, edema, and eosinophilic cellular and karyorrhectic necrotic debris. Adjacent pleura also contains abundant loose (edematous) to hyalinized fibrous connective tissue with plump reactive fibroblasts and numerous small caliber vessels (granulation tissue). Multifocally, vessel lumina are congested and contain enmeshed neutrophils, macrophages, and fewer lymphocytes and plasma cells, and endothelial cells are often hypertrophic (reactive). Villous projections are multifocally lined by hypertrophied mesothelial cells that occasionally pile up to 3 cell layers (mesothelial hyperplasia).

 

MORPHOLOGIC DIAGNOSIS: Pleura: Pleuritis, proliferative, pyogranulomatous, and necrotizing, chronic, diffuse, severe, with granulation tissue, mesothelial hyperplasia, sulfur granules, and large colonies of filamentous bacteria, beagle, canine.

 

ETIOLOGIC DIAGNOSIS: Actinomycotic pleuritis

 

CAUSE: Actinomyces sp.

 

GENERAL DISCUSSION:

• Actinomyces is a slender, filamentous, branching, gram positive, lightly basophilic rod; acid fast negative
• Actinomyces sp. are normal flora of oral mucus membranes, tooth surfaces (dental plaque), upper respiratory tract, and the gastrointestinal tract 
• Hunting dogs or dogs with access to outdoor, rural environments
• Commonly recovered organisms are Actinomyces, Nocardia, and Bacteroides spp.

 

PATHOGENESIS: 

 

TYPICAL CLINICAL FINDINGS:

• Chronic fever, emaciation, lethargy, dyspnea and fistulous tracts
• Cough and dyspnea 

 

TYPICAL GROSS FINDINGS:

• Pyothorax; generally bilateral; pneumonia absent or minor 
• Exudate is bloody and opaque (“tomato soup”) to creamy or darkly serofibrinous; pleural surfaces are thickened and velvety, red or gray-yellow and fibrotic; yellow “sulfur” granules often present in exudate; “sulfur” granules are aggregated mats of bacteria surrounded by eosinophilic hyalinized material
• Cutaneous or subcutaneous nodules with deep cellulitis that may be ulcerated or fistulated (Faccin, 2023)

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Pyogranulomatous pleuritis and mediastinitis; infrequent aggregates of filamentous bacteria (“sulfur granules”); villous-like projections with abundant fibrovascular tissue
• Skin or mucosa: Pyogranulomatous inflammation composed of neutrophils and surrounded by epithelioid macrophages with intracellular and extracellular bacteria; Splendore-Hoeppli reaction (Faccin, 2023)
  1. Rarely Actinomyces can form hyphae-like filaments in tissue

 

ADDITIONAL DIAGNOSTIC TESTS:

• Cytology: Long, slender, filamentous rods; gram-positive, acid-fast negative (Nocardia is variably acid-fast); silver stain
• Anaerobic culture
• Bacterial histochemical stains: Gram stain (Brown-Brenn), geimsa, and silver stains à clumps of intermittently branching, tangled, filaments

 

DIFFERENTIAL DIAGNOSIS:

• Pleuritis in dogs: Bite wounds, esophageal perforation, or bacteremia
• Sparganosis (larval cestodes of genus Spirometra) àpleural thickening due to chronic inflammation with presence of plerocercoids/spargana

• Nocardia sp. (I-B05):  Slender, beaded, filamentous, gram-positive, aerobic and variably acid-fast (Fite-Faraco, modified Kinyoun stain); sulfur granules rare; high mortality

 

COMPARATIVE PATHOLOGY:

Actinomyces sp. in other animals:

• Cats: Pyothorax and subcutaneous abscesses secondary to bite wounds are the most common clinical presentations; there is often yellow to sanguineous exudate without a granulomatous mass
  • Other causes of pleuritis in cats: FIP, Pasteurella multocida, Streptotoccus sp., Staphylococcus sp.
• Cattle: Actinomyces bovis causes lumpy jaw
• Swine: Actinomyces suis causes mastitis in sows; mammary tissue is markedly swollen, and there is granulation tissue
• Horses: A. bovis may be recovered with Brucella abortus and B. suis from the supraspinous bursa of horses with "poll evil" or "fistulous withers"
• Otter: Actinomyces sp. with closest match to A. bowdenii was isolated in river otter in British Columbia
• Hamster: Actinomyces bovis found in cutaneous and cervical abscesses
• Rabbit: Cause of granulomatous osteitis of the head, spinal cord, and extremities, as well as tooth-related abscesses in domestic rabbits
• Koala: Pyogranulomatous lobar pneumonia; novel Actinomyces cultured (Stephenson, 2021)
• Non-human primates:
  • Pyometra in a rhesus monkey: Actinomyces spp. along with Staphylococcus aureus were isolated as probable causative organisms 
  • Granulomatous lesions: face of a capuchin and spider monkey, abdominal wall of a moor macaque, hemorrhagic enteritis in a Macaca maura
    • Pyogranulomas with necrotic centers and sulfur granules are the typical microscopic lesion

 

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH, eds. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley-Blackwell; 2016:79,186,271. 
2. Caswell JL, Williams KJ. Respiratory system. In: Maxie ME, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, PA: Elsevier; 2016:521-522.
3. Cowell RL, Arndt TP. Selected infectious agents. In. Cowell RL, ed Diagnostic cytology and hematology of the dog and cat. 4^th ed. St Louis, MO: Elsevier; 2014:49.
4. Faccin M, Wiener DJ, Rech RR, Santoro D, Rodrigues Hoffmann A. Common superficial and deep cutaneous bacterial infections in domestic animals: A review. Vet Pathol. 2023:1-16.
5. Fisher DJ. Cutaneous and Subcutaneous Lesions. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:75-102. 
6. 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; 2022:638,642. 
7. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie ME, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier; 2016:637-639.
8. Abee CR, Mansfield K, Tardif S, Morris T. Nonhuman Primates in Biomedical Research: Volume 2: Diseases. 2^nd ed. San Diego, CA: Elsevier; 2012:120.
9. Raskin RE. Skin and Subcutaneous Tissues. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 3rd ed. St. Louis, MO: Elsevier; 2016:41-97. 
10. Stephenson T, Lee K, Griffith JE, et al. Pulmonary Actinomycosis in South Australian Koalas (Phascolarctos cinereus). Vet Pathol. 2021; 58(2):416-422.

 

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