JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
AUGUST 2022
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 viable and degenerate neutrophils, moderate numbers of epitheliod 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 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 is most commonly isolated, which includes N. brasiliensis, N. otitidis-caviarum, N. nova and N. farcinica
PATHOGENESIS:
- Most commonly an opportunistic infection produced by wound contamination, inhalation, or ingestion
- Spread by direct extension or hematogenous dissemination
- Nocardia 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 with 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
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 may be present in pleural or peritoneal space or within abscesses
- Nocardia 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 is not associated with Splendore-Hoeppli phenomenon
- Vascular necrosis and ischemia with invasion of blood vessels
ADDITIONAL DIAGNOSTIC TESTS:
- Culture, cytology, or PCR
- Nocardia appears as beaded, branching filaments that stain poorly on H&E, Gridley’s fungal, or PAS; B&B or methenamine silver preparations are best for demonstrating the organism
- Nocardia are often partially acid-fast, but must use a Fite-Faraco modification of the Ziehl-Neelsen technique
DIFFERENTIAL DIAGNOSIS:
- Actinomycosis is the primary differential for nocardiosis: Actinomyces is gram positive, non-acid fast, 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
- 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, 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. It is generally systemic involving at least 2 organs most frequently in lungs and thoracic lymph nodes. If infections that lead to death, it is seen in the brain.
- Similarly, lung lesions have been seen in juvenile hooded seals that are immune suppressed.
- Nocardia asteroides has been associated with abortion in horses, cattle, sheep, and swine, often with no other signs in the dam
- Causes granulomatous mastitis in cattle and small ruminants
- Reported to cause granulomatous lymphadenitis in ungulates
- NHPs: asteroids; pyogranulomas in multiple organs with disseminated infection; rarely pulmonary without systemic involvement
REFERENCES:
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- Edwards DF. Actinomycosis and nocardiosis. In: Infectious Diseases of the Dog and Cat, 4th ed. St Louis, MO: Saunders Elsevier; 2006:492-495.
- 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.
- Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat Clinical and Histopathologic Diagnosis. 2nd ed. Ames, IA: Blackwell Publishing Professional; 2005:272-275.
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- Scott DW, Miller WH, Griffin CE. In: Muller and Kirk’s Small Animal Dermatology. 6th ed. Philadelphia, PA. W.B. Saunders Company; 2001:323-324.
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