JPC SYSTEMIC PATHOLOGY

SPECIAL SENSES

April 2024

S-F02 (NP)

Signalment (N27784F): Unknown age and gender Doberman pinscher

HISTORY: Presented with multiple non-pruritic, draining, fluctuant nodules and fistulous tracts on the face, trunk, and extremities along with exercise intolerance and ocular discharge. The right eye had a grade 2/4 flare, rubeosis iridis, and conjunctival injection. The pupil would not dilate and the fundus could not be assessed. The left eye had a detached retina.

HISTOPATHOLOGIC DESCRIPTION: Eye: Diffusely, the retina is separated from the hypertrophic retinal pigmented epithelium by copious exudate composed of numerous viable and degenerate neutrophils, macrophages, rare multinucleated giant cells (foreign body type), viable and degenerate yeast (within macrophages and extracellular), and abundant eosinophilic homogenous to fibrillar and lacy material (fibrin and edema). The yeast are 12-18 µm diameter with a 2-3 µm thick wall, a centrally located eosinophilic or basophilic granular nucleus, and rare broad base budding. Diffusely, the overlying detached retina is convoluted, with disorganized or lost cell layers that are expanded by similar inflammation, fibrin, edema and congestion. The choroid, ciliary body, and iridial stroma are edematous, congested, and are infiltrated by numerous plasma cells, macrophages, and fewer neutrophils and lymphocytes. The posterior and anterior chambers contain abundant fibrin. Overlying the anterior surface of the iris is a proliferation of fibrovascular tissue measuring up to ~40µm (pre-iridal fibrovascular membrane). The periphery of the cornea contains numerous small blood vessels lined by plump endothelial cells (vascularization), separated by loosely arranged collagenous stroma with plump fibroblasts (fibroplasia) and rare lymphocytes, macrophages, and neutrophils. This inflammation extends throughout the corneal stroma and there is loss of corneal stromal clefts (edema).

MORPHOLOGIC DIAGNOSIS:

1. Eye: Endophthalmitis, pyogranulomatous, diffuse, severe, with retinal detachment, pre-iridal fibrovascular membrane and numerous budding yeasts, Doberman pinscher, canine.

2. Eye, cornea: Keratitis, chronic-active, multifocal, mild with vascularization and edema.

ETIOLOGIC DIAGNOSIS: Mycotic ophthalmitis

CAUSE: Blastomyces dermatitidis

CONDITION: North American blastomycosis

GENERAL DISCUSSION:

Systemic mycotic disease caused by a dimorphic soil saprophyte (see P-F05 and I-F06 for discussion on pulmonary and integumentary manifestations)
Endemic areas are centered around wet and swampy areas to include Mississippi, Missouri, Ohio River valleys, and mid-Atlantic states; also found in Europe, Asia, the Middle East, and Africa
Most frequently reported cause of intraocular mycosis in dogs; mainly young outdoor dogs; rare in cats
Ocular manifestations reported in up to 50% of dogs with systemic blastomycosis

PATHOGENESIS:

Mycelial spores (conidia) inhaled à conidia are either rapidly phagocytized and killed by macrophages/neutrophils, or they rapidly convert to yeast form (yeast form is resistant to phagocytosis/killing) à proliferate in lungs à may disseminate systemically via leukocyte trafficking (macrophages) via blood and lymphatics
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

TYPICAL CLINICAL FINDINGS:

Clinical signs reflect the involved tissue; respiratory symptoms from granulomatous pneumonia are most common
Eye: Anterior uveitis, panophthalmitis, chorioretinitis, retinal detachment, secondary glaucoma, and optic neuritis
Blastomycosis has been associated with pulmonary embolism in a dog

TYPICAL GROSS FINDINGS:

Pyogranulomatous or granulomatous endophthalmitis, granulomatous optic neuritis, and exudative retinal separation

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Diffuse pyogranulomatous or granulomatous endophthalmitis with chorioretinitis, hyalitis, exudative retinal separation, cataract(s), and often granulomatous optic neuritis
Anterior uveitis usually less pronounced than choroiditis
Lens capsule rupture
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; most commonly found in choroid

ADDITIONAL DIAGNOSTIC TESTS:

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

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
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

DIFFERENTIAL DIAGNOSIS:

Mycotic ocular infections:

Cryptococcus neoformans (S-F01): Predominantly within retina, choroid, and optic nerve; often no inflammation; yeast are 5-20 µm with narrow based budding and thin cells well and a thick capsule (halo)
Coccidioides immitis: Rare; generally a more destructive lesion than other mycoses; often suppurative panophthalmitis with pyogranulomatous reaction around fungal spherules; endosporulation; larger than Blastomyces dermatitidis (30-100 µm)
Histoplasma capsulatum: Lymphoplasmacytic and histiocytic choroiditis or panuveitis, retinal separation, optic neuritis; small yeasts (2-4 µm) within macrophages
Prototheca sp. (S-M03): Algae causing marked inflammation in the choroid, retina, and subretinal space; ovoid or angular organism (8-20 µm)
Generalized disease with Aspergillus sp. and Candida sp. may involve the eyes in immunosuppressed animals

COMPARATIVE PATHOLOGY:

Cat: Rare cause of ocular mycosis
Disseminated blastomyocosis has been reported in numerous animal species

References:

Barger AM. Musculoskeletal system. In: Raskin RE, Meyer DJ, Boes KM, eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. St. Louis, MO: Elsevier; 2023:490, 503.
Blauvelt M, Messick JB. The Lymph Nodes. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2020:174-175, 177.
Boes KM. Body Cavity Fluids. In: Raskin RE, Meyer DJ, Boes KM, eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. St. Louis, MO: Elsevier; 2023:254.
Boes KM. Respiratory system. In: Raskin RE, Meyer DJ, Boes KM, eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. St. Louis, MO: Elsevier; 2023:189, 219-221.
Conrado FO. Fecal and Rectal Cytopathology. In: Raskin RE, Meyer DJ, Boes KM, eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. St. Louis, MO: Elsevier; 2023:394.
De Lorenzi D, Pintore L. Nervous system. In: Raskin RE, Meyer DJ, Boes KM, eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. St. Louis, MO: Elsevier; 2023:545.
Di Terlizzi R, English K, Cowell RL, et al. Transtracheal and bronchoalveolar washes. In: Valenciano AC, Cowell RL, eds. Cowell and Tyler’s Diagnostic Cytology and Hematology of the Dog and Cat. St. Louis, MO: Elsevier; 2020:261.
Ewing PJ, Meinkoth JH, Cowell RL, Tyler RD. The Kidneys. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2020:371-373.
Fisher DJ. Cutaneous and Subcutaneous Lesions. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2020:80-81.
Haddad JL, Roode SC, Grindem CB. Bone Marrow. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2020:502.
Hostetter SJ. Oral Cavity, Gastrointestinal Tract, and Associated Structures. In: Raskin RE, Meyer DJ, Boes KM, eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. St. Louis, MO: Elsevier; 2023:312.
Labelle P. The eye. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7^th Ed. St. Louis, MO: Elsevier; 2022:1415-1416.
Levine GJ, Cook JR. Cerebrospinal Fluid and Central Nervous System Cytology. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2020:221.
Raskin RE, Conrado FO. Integumentary System. In: Raskin RE, Meyer DJ, Boes KM, eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. St. Louis, MO: Elsevier; 2023:50-51.
Stanton JB, Zachary JF. Mechanisms of Microbial Infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7^th Ed. St. Louis, MO: Elsevier; 2022:280.
Wilcock BP, Njaa BL. Special senses. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. Vol 1. St. Louis, MO: Elsevier Inc; 2016:449-450.