JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

January 2025

I-B05

Signalment (JPC# 21474-3): Dog

HISTORY: This dog had fistulous cutaneous tracts that exuded a purulent, blood-tinged fluid.

HISTOPATHOLOGIC DESCRIPTION: Haired skin: Infiltrating the subcutis and panniculus carnosus are multifocal to coalescing nodular aggregates of numerous intact and degenerate neutrophils, moderate numbers of epithelioid macrophages, and fewer lymphocytes, plasma cells, and eosinophils. There is multifocal loss of architecture with replacement by eosinophilic cellular and karyorrhectic debris (lytic necrosis) and eosinophilic beaded to fibrillar material (fibrin). Similar inflammatory cells are scattered throughout the subcutis. Collagen bundles are loosely separated by clear space and ectatic lymphatics (edema). Occasionally, most often at the periphery of necrotic areas, there are scattered clusters of tangled, faintly eosinophilic, 1 um x 8-15 um, filamentous bacteria. Myofibers of the panniculus carnosus are multifocally shrunken (atrophy) or fragmented, hypereosinophilic with a pyknotic nucleus (necrosis).

MORPHOLOGIC DIAGNOSIS: Haired skin, subcutis: Panniculitis, pyogranulomatous, nodular, multifocal, moderate, with filamentous bacteria, breed unspecified, canine.

ETIOLOGIC DIAGNOSIS: Subcutaneous nocardiosis

CAUSE: Nocardia sp.

GENERAL DISCUSSION:

• Nocardia spp. is a saprophytic actinomycete that is present in most environments and produces a suppurative to granulomatous, opportunistic infection
• Gram-positive, non-motile, aerobic, 0.5-1 um diameter, branching, filamentous rods that are variably acid-fast (Fite Faraco)
• N. asteroides complex types I-VI are most commonly isolated, which includes N. brasiliensis, N. otitidis-caviarum, N. nova and N. farcinica

PATHOGENESIS:

• Commonly an opportunistic infection resulting from wound contamination, inhalation, or ingestion
• Spread by direct extension or hematogenous dissemination
• Nocardia spp. are facultative intracellular pathogens that survive within phagocytic vacuoles of macrophages and neutrophils by inhibiting phagosome-lysosome fusion, neutralizing phagosome acidification, resisting oxidative burst, and altering lysosomal enzymes
• Specific resistance is cell-mediated; antibody confers little protection
• Severe and disseminated nocardiosis is associated with immune suppression, especially due to administration of immunosuppressive or immunomodulatory medications

TYPICAL CLINICAL FINDINGS:

• Skin infections with ulcerated nodules and abscesses with draining tracts that occur at wound sites especially on distal limbs and head; can extend into and involve underlying bone
• Pulmonary nocardiosis is characterized by subacute to chronic respiratory infection with mucopurulent oculonasal discharge, dyspnea, diarrhea, and hyperthermia
• Systemic or disseminated nocardiosis involves lesions in two or more sites within the body; typically associated with pulmonary disease; most frequently involved extrathoracic organs include skin and subcutaneous tissue, kidney, liver, spleen, lymph node, CNS, bone, and joints
• Co-infection with canine distemper virus is commonly reported
• Nocardia spp. are a common cause of osteomyelitis.

TYPICAL GROSS FINDINGS:

• Skin abscesses with draining fistulous tracts
• Lesions of internal organs are numerous, subserosal, discrete to coalescing, raised, white nodules that are caseous to purulent on cut surface
• Lymph nodes are often massively enlarged with a caseous to purulent core
• Reddish-brown exudate or effusion may be present in pleural or peritoneal space or within abscesses (Vogel, 2024).
• Nocardia spp. rarely forms granules; granules (“sulfur granules”) are more suggestive of Actinomyces spp. Infection

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Induces predominately suppurative necrosis with variable granulomatous features
• Abundant bacteria are present in necrotic and suppurative tissue
• Bacteria: beaded, branching filaments individually or in tangled aggregates and shorter, coccobacillary forms; bacteria tend to be distributed singly and can be difficult to identify on H&E-stained sections
• Rosette-like arrays of colonies (sulfur granules) are not as common as in actinomycosis, and Nocardia spp. is not associated with Splendore-Hoeppli phenomenon (Faccin, 2023).
• Vascular necrosis and ischemia with invasion of blood vessels

ADDITIONAL DIAGNOSTIC TESTS:

• Culture, cytology, or PCR
• Nocardia sp. appears as beaded, branching filaments that stain poorly on H&E, Gridley’s fungal, or PAS; Gram stain or methenamine silver preparations are best for demonstrating the organism
• Mat-like colonies of filamentous, Gram positive organisms is indicative of Nocardia spp or Actinomyces spp.
• Nocardia spp. are often partially acid-fast but must use a Fite-Faraco modification of the Ziehl-Neelsen technique; Acid fast positivity is what helps differentiate Nocardia spp. from Actinomyces spp., which are acid fast negative (Faccin, 2023).
• Nocardia spp. are gram positive (Faccin, 2023).

DIFFERENTIAL DIAGNOSIS:

• Actinomycosis is the primary differential for nocardiosis: Actinomyces is gram positive, acid-fast negative, anaerobic, and frequently forms sulfur granules; fibrosis surrounding granulomas tends to be more common and severe than in nocardiosis
• Rhodococcus equi is morphologically and histochemically similar; Rhodococcus is gram positive, partially acid-fast, and pleomorphic, ranging from short coccobacilli to filamentous mycelial bacilli; it is usually wider than Nocardia spp.
• Other causes of granulomatous inflammation: foreign body reactions, deep mycotic infections, infection caused by opportunistic mycobacteria, botryomycosis, or other chronic bacterial or fungal infections; rule out via culture, cytology, and histopathology

COMPARATIVE PATHOLOGY:

• Disease is reported in humans, dogs, cats, cattle, goats, horses, pigs, marine mammals, gazelles, llamas, fish, a raccoon, a buffalo calf, a reindeer, numerous bird species, and in wild boar
• Nocardiosis is more common in dogs than in cats
• Marine Mammals: Nocardiosis has been reported in cetaceans to include Atlantic bottled nose dolphins, beluga whales and killer whales
• Generally systemic involving at least 2 organs (most frequently in lungs and thoracic lymph nodes); when infections that lead to death, organisms can be found in the brain
• Lung lesions have been seen in juvenile hooded seals that are immunosuppressed
• Nocardia asteroides has been associated with abortion in horses, cattle, sheep, and swine, often with no other signs in the dam; recent report of Nocardia farcinia abortion in a goat (Vogel, 2024)
• Causes granulomatous mastitis in cattle and small ruminants; more commonly responsible for mastitis in cattle than other Nocardiosis disease presentations (Faccin, 2023).
• Reported to cause granulomatous lymphadenitis in ungulates
• NHPs: N. asteroids; pyogranulomas in multiple organs with disseminated infection; rarely pulmonary without systemic involvement
• Recently reported in ferrets to cause pyogranulomatous inflammation in numerous organs (Juan-Sallés, 2025)
• In birds, the most common isolate is Nocardia asteroids and the most common site of infection is the lungs with secondary dissemination to other organs

REFERENCES:

1. Colegrove K. Burdick-Huntington KA. Rowe W. Siebert U. Pinnipediae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier; 2018:582.
2. 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;60(6):796-811.
3. Foster RA, Premanandan C. Female Reproductive System and Mammae. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier Mosby; 2022:1185.
4. Hargis AM, Myers S. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1077.
5. Juan-Sallés C, Martínez-Chavarría LC, Montesinos A, Giner J, Valls X, Bermúdez J, Hernández-Castro R, Ardiaca M, González V, Villora J, Marco A. Nocardiosis in domestic ferrets (Mustela putorius furo). J Comp Pathol. 2025;217:1-10.
6. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Saunders Elsevier; 2016:637-638.
7. Raskin RE, Meyer DJ, eds. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 3rd ed. St. Louis, MO: Elsevier; 2016:43,145,167,199,364.
8. Schmidt R, Struthers, JD, Phalen DN. Pathology of Pet and Aviary Birds. 3rd ed. Hoboken, NJ: John Wiley & Sons, Inc.; 2024;119,133,135.490,523,575.
9. Simmons J, Gibson SV. Bacterial and mycotic diseases. In: Bennett BT, Abee CR, and Henrickson R. Nonhuman Primates in Biomedical Research: Diseases. 2nd ed. London, UK: Academic Press; 2012:119.
10. St. Leger J, Raverty S, Mena A. Cetacea. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier; 2018:557.
11. Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:45-46,76-80,205,237,273-275.
12. Vogel H, Daniels JB, Frank CB. Nocardia farcinica abortion in a goat. J Vet Diagn Invest. 2024;36(1):128-130.

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