JPC SYSTEMIC PATHOLOGY
SPECIAL SENSES SYSTEM
Signalment (JPC #1743577): Labrador mix
HISTORY: This Labrador mix developed neurological signs including papillitis, which eventually progressed to blindness. At necropsy, the animal also had meningitis.
HISTOPATHOLOGIC DESCRIPTION: Eye: Expanding the optic nerve meninges, surrounding the nerve, and extending into perineural adipose tissue are numerous epithelioid macrophages, fewer lymphocytes and plasma cells, occasional multinucleated giant cells, and rare neutrophils. There are numerous extracellular and intrahistiocytic, round to crescentic, non-staining, 5-20 um diameter yeast, with thin, birefringent walls and rare narrow-based budding. Yeasts are surrounded by a clear, 5-10 um wide halo. Focally within the choroid, there is a single, 70 by 80 um nodule composed of moderate numbers of previously described inflammatory cells and yeast that elevates the retinal pigmented epithelium.
MORPHOLOGIC DIAGNOSIS: Eye, optic nerve: Meningitis, granulomatous, diffuse, moderate, with focal choroiditis, perineural steatitis, and myriad yeast, etiology consistent with Cryptococcus neoformans, Labrador mix, canine.
ETIOLOGIC DIAGNOSIS: Ocular cryptococcosis
CAUSE: Cryptococcus neoformans
SYNONYM: European blastomycosis, torulosis
- Cryptococcus neoformans is a worldwide cause of subacute to chronic mycotic infections in a wide variety of animals (especially cats) and humans
- neoformans is a saprophytic, 5-20 um wide, yeast-like basidiomycete fungal organism that reproduces by narrow-based budding; in tissues, organisms are round to crescentic, thin walled, and surrounded by a thick, 5-10 um wide, mucopolysaccharide capsule forming a clear halo that imparts the characteristic “soap bubble” appearance
- There are two variants: Cryptococcus neoformans neoformans associated with pigeon and other bird droppings, and Cryptococcus neoformans var. gattii, found in debris under eucalyptus trees
- Infections occur primarily in immunocompromised animals and may be localized or disseminated; there is a predilection for the respiratory (particularly the nasal region) and central nervous systems; cutaneous and ocular lesions occur less frequently
- Transmission generally occurs via inhalation of contaminated dust or soil enriched with pigeon droppings; the organism settles in the nasal mucosa or alveoli, inducing local granulomas
- The capsule thickness and release of glycoprotein into the circulation interfere with antigen presentation, subsequent immune response, and elimination of the organism
- Direct or hematogenous dissemination causes secondary infection of other organs, such as the CNS, eyes (choroid, optic nerve), lymph nodes, mammary glands, skin, and bone
- In cats especially, extension is often through the cribiform plate > olfactory bulbs > olfactory tracts > meningitis
- Organisms may persist in ocular tissues due to anterior chamber-associated immune deviation that results in antigen-specific suppression of delayed-type hypersensitivity; anterior chamber-associated immune deviation is thought to have evolved to prevent excessive inflammation in the eye and destruction of normal tissues; the disadvantage is that it limits the ability of the eye to eliminate certain pathogens (fungi, parasites, intracellular bacteria) > pathogens remain in the eye > reservoir of reinfection
TYPICAL CLINICAL FINDINGS:
- Ocular: Papillitis, optic neuritis, chorioretinitis, anterior uveitis, blindness, mydriasis, posterior synechia, retinal hemorrhage and detachment, endophthalmos due to retrobulbar abscess
- CNS: Disorientation, circling, ataxia, paresis/paralysis, Horner’s syndrome
- Respiratory: Unilateral or bilateral rhinitis, nasal swelling, mucopurulent discharge, sneezing
- Cutaneous: Ulcerated dermal nodules, usually on the head and often associated with lymphadenopathy
- Mammary (especially cows): Intractable mastitis and supramammary lymphadenitis
TYPICAL GROSS FINDINGS:
- Typical presentation is of rapidly growing, often multiple, pale, gelatinous to mucoid, granulomatous or tumor-like masses in the affected organs; the eye, the optic nerve, meninges, retina, and choroid may be diffusely or multifocally thickened by gelatinous material that may displace surrounding structures
- In the CNS, the meninges are similarly thickened, and organisms and inflammation may displace underlying cerebral tissues or invade adjacent bone
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Numerous ovoid or spherical, 5-20 um, thick-walled, yeast-like organisms surrounded by a 5-10 um thick gelatinous capsule with occasional narrow-based budding and forming “soap bubble” masses
- Minimal to moderate mononuclear, granulomatous, or pyogranulomatous inflammation
- Mucicarmine, PAS, and alcian blue-positive staining of the capsule, giving it a radiating, spoke-wheeled appearance
ADDITIONAL DIAGNOSTIC TESTS:
- Serology: Direct ELISA, latex agglutination, FA
- Cytology: Mucicarmine, India ink
Causes of Fungal/Algal Intraocular Infections:
- Blastomyces dermatitidis: Most common cause of intraocular mycosis in dogs and causes diffuse granulomatous to pyogranulomatous endophthalmitis with retinitis, exudative retinal separation, and granulomatous optic neuritis; buds are broad-based; yeast walls may demonstrate mild mucicarmine staining, but there is no capsule
- Histoplasma capsulatum: Rarely causes ocular disease and is less destructive than Cryptococcus or Blastomyces, with lesions centered on the choroid and dominated by plasma cells and macrophages
- Coccidioides immitis: Large, 5-50 um wide, non-encapsulated yeast with reproduction via endosporulation; rarely affects the eye, causing pyogranulomatous inflammation that is more destructive than Cryptococcus or Blastomyces
- Prototheca zopfii: Colorless, refractile, 2-20 um wide, endosporulated algal organisms with tripartite cell wall division; argyrophilic and PAS-positive; causes minimal to intense granulomatous inflammation
- Aspergillus terreus: Disseminated granulomatous infection in young to middle-aged German Shepherds with chronic anterior and posterior uveitis and diskospondylitis
- Cats: The most common systemic mycosis in cats; causes primarily nasal lesions with direct extension to the CNS
- Horses: Primarily nasal lesions with direct extension to the CNS; also causes placentitis and abortions
- Cattle: Associated with intractable mastitis with supramammary lymphadenopathy and rare dissemination to other regions
- Rabbits: Have been used as a model for chronic cryptococcal meningitis; normally highly resistant to C. neoformans infection
- Humans: Usually localized in the meninges with pulmonary lesions less common; often underlying immunodeficiency
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