P-F05

Signalment (JPC #3141624): 1-year-old Labrador retriever dog

HISTORY: This dog presented on emergency for respiratory distress and died during hospitalization.

HISTOPATHOLOGIC DESCRIPTION: Lung: Multifocally affecting 50% of the section, the pulmonary parenchyma, to include alveoli, alveolar septa, terminal bronchioles, and the interstitium, is expanded or replaced by a densely cellular exudate composed of macrophages (often epithelioid) and multinucleated giant cells (foreign body and Langhans types), neutrophils, and fewer lymphocytes and plasma cells admixed with eosinophilic cellular and karyorrhectic debris (necrosis), eosinophilic fibrillar material (fibrin), hemorrhage, and edema. There are numerous intracytoplasmic (within macrophages and multinucleate giant cells) and extracellular round, 5-20 µm yeast that have a 1 µm refractile wall, basophilic granular protoplasm and occasional broad-based budding. In less affected areas, alveoli contain abundant seroproteinaceous edema fluid and increased numbers of foamy alveolar macrophages. Vessels are diffusely congested and multifocally are surrounded by ectatic lymphatics and increased clear space (edema).

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, pyogranulomatous, multifocal to coalescing, severe, with numerous intrahistiocytic and extracellular broad-based budding yeasts, Labrador retriever, canine.

ETIOLOGIC DIAGNOSIS: Pulmonary blastomycosis

CAUSE: Blastomyces dermatitidis

SYNONYMS: North American blastomycosis

GENERAL DISCUSSION:

An infectious, non-contagious disease most frequently reported in dogs, especially young, large breeds housed outside or used for hunting; however, numerous cases in many mammalian species have been documented
Endemic to the midwestern and northern United States and Canada, including the Mississippi, Ohio, and St. Lawrence river valleys, northern Ontario, and the Great Lakes region; also occurs in Africa, the Middle East, and occasionally Europe; outbreaks associated with recently disturbed soil
Dimorphic fungus (thermally dependent) that exists in a contagious mycelial (mold) form in cooler temperatures and converts to non-contagious yeast form above 37^oC (body temperature)

3 disease forms: pulmonary (most common), disseminated, and cutaneous (rare)

PATHOGENESIS:

Mycelial spores (conidia) inhaled from soil à trapped in mucus layer of terminal bronchioles via centrifugal and inertial turbulence à conidia bind to alveolar macrophages via surface adhesins (e.g. BAD1) à conidia are either rapidly phagocytized and killed by macrophages/neutrophils (conidia readily phagocytized/killed), or they rapidly convert to yeast form (yeast are resistant to phagocytosis/killing) à proliferate in lungs à may disseminate systemically via leukocyte trafficking (macrophages) via blood and lymphatics to lymph nodes, eyes, skin/subcutaneous tissues, bones, and joints most commonly; other organs are less commonly affected

Virulence factors:
- BAD-1 (Blastomyces adhesion factor 1) surface protein mediates adhesion to alveolar macrophages
- Alpha-1,3-glucan within yeast cell wall and melanin are protective against phagocytosis/killing

TYPICAL CLINICAL FINDINGS:

Pulmonary disease: Dyspnea, nasal discharge, chronic coughing, respiratory distress

Hypercalcemia of granulomatous disease due to the excessive production of 1,25 dihydroxycholecalciferol by macrophages

TYPICAL GROSS FINDINGS:

Lung: Most commonly infected organ; granulomatous to pyogranulomatous interstitial pneumonia with yellow-white, variably sized, randomly distributed granulomas
Disseminated form: Can reach the lymph node (regional lymphadenopathy with expansile yellow-white granulomas), eye (S-F02), skin and subcutaneous tissue (I-F06), bone, and brain; lesions are typical granulomas or pyogranulomatous foci

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Yeast: 5-15 µm (occasionally up to 30 µm) in diameter, round, non-encapsulated, with a distinct 1-µm thick wall, granular protoplasm completely or partially filling the center; broad based budding; extracellular and occasionally within macrophages, often at the center of inflammatory focus
Granulomatous to pyogranulomatous inflammation depending on site and chronicity

ADDITIONAL DIAGNOSTIC TESTS:

Histochemical stains: Grocott methenamine silver (GMS), Periodic-Acid Schiff (PAS)

Cytology of transtracheal wash or lymph node aspirate; granulomatous to pyogranulomatous inflammation; yeast are spherical, 5-20µm, deeply blue with thick, refractile double contoured wall and broad based budding; typically extracellular, but may rarely be within macrophages
PCR
Serology: False negatives common
Enzyme immunoassays for galactomannan: Widely used clinically; sensitivity in urine 94%, serum 87%
Culture: NOT recommended due to the danger of infection from the mycelial form

DIFFERENTIAL DIAGNOSIS:

Gross appearance:

Metastatic neoplasia
Granulomatous pneumonia of other etiology

Cryptococcus neoformans (P-F04): Narrow base budding, thick carminophilic capsule; mutants of Cryptococcus that lack the characteristic thick capsule may closely resemble B. dermatitidis
Coccidioides immitis/C. posadasii (P-F03): Spherules (containing endospores) are larger (20-200µm) with no budding

Histoplasma capsulatum var. capsulatum (P-F02, 2-5µm) and var. duboisii (I-F13, 8-15µm): Narrow base budding, intrahistiocytic
Mycobacterium sp. (P-B10): Small, acid fast bacilli

Prototheca sp. (D-F03, S-M03, U-M25): Larger with characteristic tripartite endospore morphology

COMPARATIVE PATHOLOGY:

Occasionally reported in cats, horses, coyotes; rarely reported in bears, mice, rhesus macaques, chinchillas, and other animals
NHP: Single report in a rhesus macaque that had been previously housed outdoors near the Mississippi river delta prior to developing pyogranulomatous pneumonia, encephalitis, and splenitis several years later

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