JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
AUGUST 2022
I-B06

 

Signalment (JPC# 4083133-00):  Two-year-old male intact beagle dog.

 

HISTORY: This hunting dog developed a large mass on the left lateral thorax wall with a draining tract into the subcutaneous tissue.

 

HISTOPATHOLOGIC DESCRIPTION: Dermis and subcutis (per contributor), left lateral thorax: Expanding the deep dermis and subcutis and extending to all borders is a poorly demarcated infiltrate of pyogranulomatous inflammation centered on a 5 x 3 mm, irregularly oval, birefringent structure composed of rectangular to oval, regularly arranged, clear cells with thick walls (foreign organic material, consistent with a grass awn). Adhering to and surrounding the foreign material are large radiating colonies of basophilic, filamentous, 1 x 3-7 µm bacteria. The foreign material and bacterial colonies are surrounded by areas of drop-out, loss of cellular architecture, and scattered eosinophilic and cellular debris (lytic necrosis) admixed with numerous viable and degenerate neutrophils, epithelioid macrophages, fewer lymphocytes, plasma cells, and occasional Langhans-type multinucleated giant cells, eosinophillic beaded fibrillar material (fibrin), hemorrhage, edema, and hemosiderin-laden macrophages. Nodules are further surrounded by haphazardly arranged, hypertrophied fibroblasts embedded in loose fibrous connective tissue with numerous small caliber vessels lined by hypertrophic endothelium (granulation tissue) that matures peripherally into thick bands of dense fibrous connective tissue (fibrosis). In less affected areas of the dermis and subcutis there are perivascular infiltrates of lymphocytes and plasma cells. Myocytes of the panniculus carnosus muscle frequently exhibit sarcoplasmic vacuolization with loss of cross striations (degeneration) or are shrunken (atrophy) and are surrounded by increased clear space and pale eosinophilic proteinaceous fluid (edema).

 

MORPHOLOGIC DIAGNOSIS: Dermis and subcutis (per contributor), left lateral thorax: Dermatitis and panniculitis, pyogranulomatous, chronic, focally extensive, severe, with large colonies of filamentous bacteria, foreign material (consistent with grass awn), and granulation tissue, beagle, canine.

 

ETIOLOGIC DIAGNOSIS: Actinomycotic dermatitis.

 

CAUSE:  Actinomyces spp.

 

GENERAL DISCUSSION: 

• Gram-positive, non–acid-fast, filamentous, anaerobic or microaerophilic bacilli
• Commensals of the oral cavity, intestine, and upper respiratory tract
• Opportunistic cutaneous, pulmonary, or disseminated infections and infections of the thorax or abdomen
• Infection usually secondary to penetrating wounds of oral mucosa or skin

 

PATHOGENESIS: 

• Infection requires disruption of mucosal or epidermal barriers by abrasion from coarse roughage (cattle), foreign body penetration (migrating grass awns in dogs), bite wounds (cats), or secondary to chronic periodontal disease
• Spreads by direct extension along tissue planes > invade adjacent structures, including bone
• Hematogenous dissemination is rarely reported
• Pneumonia may follow aspiration or esophageal perforation
• Actinomyces induce neutrophil chemotaxis, activate macrophages, and stimulate B-lymphocyte hyperplasia
• Proteolytic enzymes from the macrophages and degranulated neutrophils disrupt connective tissue, facilitating spread of the bacterium through normal tissue planes

 

TYPICAL CLINICAL FINDINGS:

• Subcutaneous: Painful lymphadenopathy associated with granulomas or abscesses, draining tracts, and radiographic evidence of osteomyelitis in underlying bone
  • Involvement of bone causes reactive bone formation
• Thoracic: Cough, dyspnea, decreased lung sounds, and pyothorax
• Abdominal: Palpable granuloma in GI tract and abdominal distension; hepatic abscess
• Retroperitoneal: Back pain and rear leg paresis/paralysis

 

TYPICAL GROSS FINDINGS:

• Lesions most common on the head, neck, and extremities
• Abscesses, cellulitis, ulcerated nodules, draining tracts, dense fibrous nodules
  • Subcutaneous, firm, lumpy, white, glistening masses
  • Thin serosanguinous to thick purulent and hemorrhagic exudate
  • White to yellow flecks (sulfur granules – grossly visible bacterial colonies)
  • Regional lymphadenopathy
• Intra-cavitary infection:
  • Red, velvety proliferation of parietal pleura, peritoneum, or omentum; visceral pleura and peritoneum are less often affected
  • Variable amount of reddish-brown exudate
• Actinomycotic mycetoma: presence of swelling (tumefaction), draining tracts, and sulfur granules together

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Pyogranulomatous dermatitis and panniculitis
  • Central cores of neutrophils surrounded by epithelioid macrophages and variable numbers of multinucleated giant cells
  • Masses of filamentous and branching, basophilic to amphophilic bacilli often surrounded by club-shaped, brightly eosinophilic Splendore-Hoeppli material
  • Dense fibrosis +/- granulation tissue between pyogranulomas
    • Fibrosis tends to be more prominent in actinomycosis compared to nocardiosis
  • Epidermis may be ulcerated and variably acanthotic
• Chronic lesions may be mineralized
• Osteomyelitis of the mandible or other bones may occur

 

ULTRASTRUCTURAL FINDINGS:

• Bacterial envelope is tri-layer and composed of an inner plasma membrane, a thick cell wall with densely staining internal layer, and a thick capsule with numerous pili

 

ADDITIONAL DIAGNOSTIC TESTS: 

• Clinicopathologic abnormalities: Nonregenerative anemia, leukocytosis, monocytosis, hypoglycemia, hypoalbuminemia, and hyperglobulinemia
• Gram stain (Brown-Brenn): Gram-positive clumps of tangled, filamentous bacteria
• Cytology: Impression smears of nodule cut surface; smears of sulfur granules
• Culture: Facultative or obligate anaerobe

 

DIFFERENTIAL DIAGNOSIS: 

• Nocardiosis: Gram-positive, filamentous, beaded rods; +/- "sulfur granules", modified acid-fast stain (Fite-Farraco) will stain Nocardia but not Actinomyces spp.
• Actinobacillosis: Gram-negative rods
• Botryomycosis (Staphylococcus): Gram-positive cocci
• Other granulomatous diseases including foreign body reactions, mycobacterial infections, and deep mycoses (fungal mycetomas)
  • Dogs – canine leproid granuloma
  • Cats – atypical mycobacteriosis, feline leprosy (I-B03), tuberculosis
  • Cattle – bovine cutaneous opportunistic mycobacteriosis, tuberculosis

 

COMPARATIVE PATHOLOGY: 

• Cattle: bovis causes mandibular and maxillary osteomyelitis (lumpy jaw) with nodules, abscesses, and draining tracts
• Pigs: Nodules commonly found on ventral abdomen and in udder
• Horses: Rare; associated with poll evil (cranial and/or caudal nuchal bursa inflammation), fistulous withers (suprasinous bursa inflammation), mandibular lymphadenitis, and abscesses
• Goats: Lesions previously described in leg and shoulder
• Koala: Recent report of pulmonary actinomycosis causing pyogranulomatous lobar pneumonia in free-ranging and captive koalas

 

REFERENCES:

1. Cheville NF. Ultrastructural Pathology: The Comparative Cellular Basis of Disease. 2^nd Wiley-Blackwell, 2009:487-491.
2. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat. 2^nd Oxford, England: Blackwell Science; 2005: 272-275.
3. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6^th Philadelphia, PA: Elsevier Saunders; 2016: 629, 636-639.
4. Stephenson T, Lee K, Griffith JE, et al. Pulmonary Actinomycosis in South Australian Koalas (Phascolarctos cinereus). Vet Pathol. 2021; 58(2):416-422.
5. Sykes JE. Actinomycosis and nocardiosis. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 4^th St. Louis, MO: Elsevier Saunders; 2012: 484-495.
6. Valentine BA. Skeletal muscle. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7^th St. Louis, MO: Mosby Elsevier; 2022: 1010, 1025.
7. Welle MM, Linder EE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7^th St. Louis, MO: Mosby Elsevier; 2022: 1173.

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