JPC SYSTEMIC PATHOLOGY
Signalment (JPC # 3104239): 14-month-old Newfoundland dog
HISTOPATHOLOGIC DESCRIPTION: SLIDE A: Haired skin: Multifocally expanding the dermis, separating and surrounding adnexal structures and extending into the markedly hyperplastic and hyperkeratotic epidermis, are multiple coalescing nodules composed of numerous epithelioid macrophages and neutrophils with fewer lymphocytes, plasma cells, and rare eosinophils, often surrounded by loosely arranged fibroblasts. Within this infiltrate are many oval, 10-20 um in diameter, yeast with a 1 um distinct double-contoured cell wall and granular protoplasm, which occasionally exhibit broad-based budding. The overlying epithelium is markedly hyperplastic with numerous anastomosing rete ridges, abundant basilar mitoses, moderate acanthosis, and a 500 um thick layer of orthokeratotic and parakeratotic hyperkeratosis. The inflammatory nodules often separate the stratum spinosum from the stratum corneum (intraepidermal abscesses); there are also multifocal intracorneal pustules, composed of degenerate neutrophils and necrotic debris. Multifocally, apocrine glands are ectatic and endothelium lining vessels is mildly hypertrophied (reactive).
Slide B (PAS): Haired Skin: Multifocally, there are PAS positive 10-20 um diameter oval yeasts with double contoured walls and broad based budding within the dermis and epidermis.
MORPHOLOGICAL DIAGNOSIS: Haired Skin: Dermatitis, pyogranulomatous, multifocal to coalescing, marked, with intraepidermal abscesses, epidermal hyperplasia, and yeast, etiology consistent with Blastomyces dermatitidis, Newfoundland, canine.
ETIOLOGIC DIAGNOSIS: Cutaneous blastomycosis
CAUSE: Blastomyces dermatitidis
SYNONYMS: Gilchrist’s disease, Chicago disease, North American blastomycosis
· Dimorphic soil saprophyte that exists in mycelial form in soil and yeast form in tissue
· Primary pathogenic dimorphic fungi:
· Blastomyces dermatitidis
· Coccidioides immitis
· Histoplasma capsulatum
· Paracoccidioides brasiliensis
· Sporothrix schenkii
· Penicillium marneffei
· Young male dogs of large and sporting breeds
· Increased numbers of cases in the fall; frequently associated with proximity to water and acidic sandy soil
· Principally a disease of North America (especially Great Lakes, Missouri, Ohio, Mississippi river valleys); has also been identified in Africa, India, Middle East and Europe
· Infection rate is 10 times greater in dogs than in man, hence the dog is important epidemiologic marker for human blastomycosis
· Most common cause of intraocular mycosis in dogs
· Primary pulmonary infection (most common)
· Inhaled conidia seed terminal bronchioles and alveoli
· Conidia rapidly germinate into yeast form and yeast phase specific virulence genes are induced with expression and secretion of blastomyces adhesion 1 (BAD 1) (formerly WI-1)
· BAD 1 mediates adhesion to phagocytic cells (CR3 and CD14), and suppresses generation of TNF alpha
· Cell wall polysaccharide alpha-glucan protects against killing by macrophages
· Yeast forms proliferate within the lungs and disseminate via the blood and lymphatic vessels, but are not contagious
· Disseminated disease
· Occurs via lymphatic and vascular channels
· In dogs, the most common sites of extrapulmonary dissemination are the lymph nodes, eyes, skin, subcutaneous tissues, bones, and joints; less common are the central nervous system, urogenital tract, spleen and mammary gland
· Localized cutaneous infection
· Cutaneous infection should be considered a manifestation of underlying disseminated visceral disease
· Rarely, can be caused by direct inoculation
TYPICAL CLINICAL FINDINGS:
· Anorexia, weight loss, coughing, dyspnea, ocular disease, lameness, skin disease
· Skin lesions include papules, nodules, plaques, ulcers, draining tracts and abscesses in the subcutis; usually multiple, frequently found on nasal planum, face, and nail beds
· Hypercalcemia of granulomatous disease due to the excessive production of 1,25 dihydroxycholecalciferol by macrophages
· Hypercoagulability in systemic blastomycosis with elevations in plasma fibrinogen concentration
TYPICAL GROSS FINDINGS:
· Ulcerated, cutaneous granulomatous papules and nodules
· Draining tracts with a serosanguinous to purulent exudate
· Occasional generalized lymphadenopathy
· The lung is the most consistently affected site with diffuse, multifocal distribution of variably sized grey-white nodules
TYPICAL LIGHT MICROSCOPIC FINDINGS:
· Mixed granulomatous to pyogranulomatous inflammatory reaction depending on site and chronicity
· Epidermis is often acanthotic or ulcerated and exudative and may contain abscesses
· Discrete granulomas or pyogranulomatous foci may be present
· Necrosis is often present
· Yeast are 5-15 um, round, non-encapsulated, distinct wall, and a granular protoplasm
· Broad based budding
· Found free in tissue and in macrophages often at the center of inflammatory focus
· Touch impression or cytologic preparations describe a round, basophilic yeast that measures 6-15 um in diameter (approximately the size of a RBC to slightly larger than a neutrophil) and has a thick, clear, refractile cell wall; organism usually stains dark blue and exhibits broad based budding
ADDITIONAL DIAGNOSTIC TESTS:
· Periodic acid‑Schiff (PAS) reaction
· Gomori’s methenamine silver (GMS)
· Gridley’s stain
· Agar gel immunodiffusion (AGID) and ELISA commercial kits available for demonstration of A-antigen (capsular antigen)
· Radioimmunoassay (RIA) for antibodies against WI-1 antigen - high sensitivity and specificity
· Culture of cytologic specimens is not recommended for in-hospital laboratories because of the danger of infection from the mycelial form of the organism
· For gross finding of multinodular lesions within the lung and other organs:
· Metastatic neoplasia: Nodules often larger and more variable in size
· For histological findings:
· Cryptococcus neoformans: 2‑20 um in diameter, thick 2‑10 um mucopolysaccharide capsule that is mucicarmine positive, narrow- based budding
· Coccidioides immitis: Spherules 20‑200 um diameter; endospores 2‑5 um in diameter
· Paracoccidioides brasiliensis (South American blastomycosis): 5‑60 um diameter, exhibit multiple narrow based budding giving the appearance of a “spoke wheel”
· Histoplasma capsulatum var. duboisii: 8‑15 um diameter, size is similar but bud from a narrow base, hourglass shape, uninucleate, vacuolated cytoplasm
· Histoplasma capsulatum var. capsulatum: 2‑5 um diameter; intracellular
· Sporothrix schenckii: Smaller and generally more pleomorphic than B. dermatitidis; often “cigar-shaped”
· Prototheca: Algae; larger with characteristic “Mercedes Benz” endospore morphology
· Lacazia (Loboa) loboi: Yeast often associate to produce “string of pearls” appearance
· Occasionally in cats
· Has been reported in rhesus monkey, horses, African and Asian lions, Siberian tiger, cheetah, snow leopard, polar bear, wolves, Indian fruit bat, ferret, Atlantic bottlenose dolphin, Steller’s and California sea lions, mice, and chinchillas (most of them are disseminated cases)
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