JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
AUGUST 2022
I-B02
SIGNALMENT (JPC #1691879): A rat.
HISTORY: The lesion involved the entire head.
HISTOPATHOLOGIC DESCRIPTION: Dermis and subcutis, head (per contributor): Expanding and effacing up to 80% of the normal architecture are multifocal to coalescing variably sized pyogranulomas centered on large, up to 200 um-diameter, colonies of 2 x 2µm basophilic cocci embedded in hyalinized, eosinophilic material that occasionally forms radiating club-shaped projections (Splendore-Hoeppli material). Pyogranulomas are characterized by a central core of eosinophilic cellular and karyorrhectic debris (lytic necrosis) with occasional areas of drop out and numerous degenerate neutrophils, surrounded by epithelioid macrophages, moderate numbers of lymphocytes and plasma cells, all of which is further surrounded by fibrosis. Adjacent fibrovascular tissue has areas of hemorrhage, fibrin, edema, with hemosiderin laden macrophages, lymphocytes and plasma cells
MORPHOLOGIC DIAGNOSIS: Dermis and subcutis, head: Pyogranulomas, multifocal to coalescing, severe, with large colonies of cocci and Splendore-Hoeppli material, breed not specified, rodent.
ETIOLOGIC DIAGNOSIS: Staphylococcal cellulitis
CAUSE: Staphylococcus aureus
CONDITION: Botryomycosis
SYNONYMS: Bacterial pseudomycosis; bacterial pseudomycetoma; bacterial pseudogranuloma
GENERAL DISCUSSION:
- Chronic pyogranulomatous disease caused by non-branching bacteria surrounded by eosinophilic, acellular material that forms radiating clubs (Splendore-Hoeppli material), affects the skin and, rarely, the viscera
- In rodents, primarily caused by staphylococcal bacteria (usually coagulase-positive Staphylococcus aureus), but other causes include Streptococcus, Pasteurella spp., Proteus spp., Pseudomonas aeruginosa, Actinobacillus lignieresii, and Bibersteinia trehalosi
- Occurs in numerous species, including cattle, sheep, horses, dogs, cats, pigs, rats, rats, mice, guinea pigs.
- The term “botryomycosis” is technically incorrect - it implies the disease is caused by a fungus, but the name has persisted since the lesions closely resemble fungal granulomas
PATHOGENESIS:
- Pathogenesis is unclear but probably results from an imbalance between the host resistance and organism virulence; host can isolate and contain the infection, but cannot eliminate it
- Usually initiated by local trauma to the skin by a bite or other wound; some are associated with a foreign body, which provides a nidus for granuloma formation
- Possible genetic predilection - certain strains of mice are more susceptible
- Urokinase plasminogen activator-deficient mice (uPA-/-) are predisposed: Absence of uPA > local response to injury is altered > unfavorable conditions in the microenvironment > ineffective wound healing > may facilitate bacterial invasion and infection
- Immunodeficiency may be involved – lesion reported in humans with HIV infection and chronic granulomatous disease
TYPICAL GROSS FINDINGS:
- Firm nodules with draining fistulous tracts that exude orange-yellow purulent exudate containing small white granules (grains)
- Involves the deep dermis and subcutis and occasionally extends to the muscle, adjacent bone, and rarely the viscera
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Nodular to diffuse pyogranulomatous dermatitis and panniculitis
- Pyogranulomas have a central core of large compact bacterial colonies (tissue granules or grains) surrounded by amorphous eosinophilic material that often forms radiating clubs (Splendore-Hoeppli material); further surrounded by many neutrophils, epithelioid macrophages, lymphocytes, plasma cells, and variable amount of fibrosis
ADDITIONAL DIAGNOSTIC TESTS:
- Culture required for definitive diagnosis
- Gram stain; Brown and Brenn (B&B) stain
DIFFERENTIAL DIAGNOSIS:
For histologic findings:
- Eumycotic mycetoma: Center of granuloma contains dense aggregates of fungal elements
- Actinomycotic mycetoma: Center of granuloma contains filamentous Gram-positive bacteria (Actinomyces, Nocardia spp.); Nocardia spp. are also weakly acid-fast
- Feline dermatophyte pseudomycetoma: Rare manifestation of Microsporum canis in Persian cats; dermatophytes evident with fungal stains
- Foreign body reaction: Inflammation surrounds foreign, anisotropic material
COMPARATIVE PATHOLOGY:
- Botryomycosis:
- Pulmonary botryomycosis is a reported, but rare, condition in horses, guinea pigs, and cattle
- Nude mice: Periorbital abscesses and nasal furunculosis due to sparse protective pelage, distorted hair shaft growth, and impaired T-cell function
- Sheep and goats: Mastitis
- Cattle: Mastitis; Actinobacillus lignieresii infection (wooden tongue) is a form of botryomycosis
- Pigs: Castration wounds; mammary glands; aural botryomycosis
- Horses: Stub of the spermatic cord in geldings (common site); neck and pectoral region (“breast boils”)
- Staphylococcal infection:
- Mice and rats: Red ulcerative skin lesions over the shoulders and rib cage, submandibular regions, head, neck, and ears.
- Gerbils: Acute, diffuse dermatitis in young gerbils with high morbidity and mortality; focal suppurative hepatitis may be present; associated with nasal dermatitis (sore nose)
- Rabbits: Mastitis (“blue breast”); can lead to fatal septicemia
- Hamsters: Cutaneous and cervical abscesses
- Chickens:
- Gangrenous dermatitis: Young growing chickens (4-20 weeks old)
- Staphylococcosis: Systemic disease in broilers usually due to break in skin or beak, or via respiratory tract.
- Omphalitis: Less common than other bacteria
- Gangrenous dermatitis: Young growing chickens (4-20 weeks old); typically secondary to immunosuppression caused by infectious bursal disease or chicken infectious anemia virus
- Cellulitis: Purulent inflammation in subcutaneous tissues
- Abscesses: Localized purulent lesions in the skin; foot common site (bumblefoot)
- Septicemia: Increase in mortality with congestion of internal organs;
- Arthritis/periarthritis/synovitis: Occurs as sequel to septicemia; any joint, tendon sheath, or synovial bursa can be affected, but usually hocks and feet; often associated with bile stasis of the liver and high numbers of large mononuclear cells on blood smears
- Discospondylitis (spondylitis): Joints of articulating thoracolumbar vertebrae and adjacent vertebrae; paresis and paralysis with pressure on the spinal cord
- Osteomyelitis: Occurs as sequel to septicemia; localize in metaphyseal vessels invading cartilage of growth plate of actively growing bones, especially proximal tibia and metatarsus
- Endocarditis: Uncommon sequel to septicemia; vegetations of aortic and/or mitral valves with emboli and infarcts in liver, brain, and spleen
- Turkeys:
- Gangrenous dermatitis
- Green liver-osteomyelitis complex: Observed at slaughter; green discoloration of the liver, arthritis/synovitis, osteomyelitis of the proximal tibia, and soft-tissue abscesses in otherwise normal-appearing turkey
- Arthritis: Occurs as sequel to septicemia; usually hocks and feet
- New world and old world monkeys:
- Infection possible with break in the skin resulting in pustular dermatitis (young animals), vaginal infections (adults), cellulitis, lymphangitis, abscessation, suppurative meningoencephalitis, and bacteremia resulting in visceral abscesses, pericarditis, arthritis, septic shock, or vegetative valvular endocarditis with septic emboli and associated infarcts
- Squirrel monkey: One report of meningitis
- Rhesus macaque: One report of dry skin, epithelial sloughing, scaling, and skin thickening due to methicillin resistant staph aureus in a whole-body-irradiated animal
- Stump-tailed macaques: Pneumonia in immune-suppressed animals naturally infected with SIV
- Apes:
- Opportunistic systemic or intra-vesicular bacterial infection secondary to monkeypox virus infection
- Meningitis, encephalitis, regional necrosis, and gliosis: Opportunistic systemic infection or extension from otitis
- Methicillin resistant staph aureus (MRSA) carried by chimpanzees and shared to humans
- Suppurative arthritis: One report in neonatal orangutan
- Porpoises: Pyogranulomatous myocarditis, necrotizing bronchopneumonia, pyelonephritis, osteomyelitis, leptomeningitis, lymph node and skeletal muscle abscesses, and suppurative epicarditis
- Killer whales: One report of suppurative pneumonia and nephritis, and tooth root abscessation in a dead stranded killer whale
- Silver carp: One report of corneal damage progressing to phthisis bulbi
REFERENCES:
- Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell Publishing; 2016:70,144, 186, 204, 228-229.
- Cooper BJ, Valentine BA: Muscle and tendon. In: Maxie MG, ed. Jubb, Kennedy, and Palmer's Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:233-4.
- Crespo R, Franca MS, Fenton H, and Shivaprasad HL. Galliformes and Columbiformes. In: Terio K, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018:
- Delaney MA, Treuting PM, and Rothenberger JL. Lagomorpha. In: Terio K, McAloose D, St. Leger J, eds, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018:494.
- Fahey MA and Westmoreland SV. Nervous System Disorders of Nonhuman Primates and Research Models. In: Abee CR, Mansfield K, Tardif S, and Morris T, eds. Nonhuman Primates in Biomedical Research. 2nd San Diego, CA; Elsevier; 2012:743.
- Foster RA and Premanandan C. Male reproductive System. In: Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1226.
- Fulton RM. Bacterial Diseases. In: Boulianne M, ed. Avian Disease Manual. 8th Jacksonville, FL; AAAP Inc.; 2019:87-88,109-111.
- Gross TL, Ihrke PJ, Walder EJ, Affolter VK. In: Skin diseases of the Dog and Cat. 2nd ed. Ames, IA: Blackwell Publishing; 2005: 275-276.
- Lowenstine LJ, McManamon R, and Terio KA. Apes. In: Terio K, McAloose D, St. Leger J, eds, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018:383, 393.
- Lowenstine LJ and Osborn KG. Respiratory System Diseases of Nonhuman Primates. In: Abee CR, Mansfield K, Tardif S, and Morris T, eds. Nonhuman Primates in Biomedical Research. 2nd San Diego, CA; Elsevier; 2012:453.
- Matz-Rensing K and Lowenstine LJ. New World and Old World Monkeys. In: Terio K, McAloose D, St. Leger J, eds, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018:363-364.
- Noga EJ. Fish Disease: Diagnosis and Treatment. 2nd Ames, IA; Wiley-Blackwell; 2010:212.
- Simmons J and Gibson S. Bacterial and Mycotic Diseases of Nonhuman Primates. In: Abee CR, Mansfield K, Tardif S, and Morris T, eds. Nonhuman Primates in Biomedical Research. 2nd San Diego, CA; Elsevier; 2012:107.
- Leger J, Raverty S, and Mena A. Cetacea. In: Terio K, McAloose D, St. Leger J, eds, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018:559.
- Welle MM and Linder KE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1173.