JPC SYSTEMIC PATHOLOGY
SIGNALMENT (AFIP Accession #3165184): An owl monkey
HISTORY: This 4-year-old, male, owl monkey (Aotus sp.) had experienced weight loss and anemia of undetermined cause over the last six months. Treatments for the latter had been unsuccessful. Recently, the animal was treated with an antibiotic for suspected sepsis. Subsequently, the monkey developed white plaques on the tongue and was euthanized.
HISTOPATHOLOGIC DESCRIPTION: Esophagus: There is marked hyperplasia of the mucosal epithelium characterized by deep rete ridge formation, acanthosis, increased intercellular clear space with prominent intercellular bridging (spongiosus), and intracellular edema with multifocal areas of erosion and ulceration and replacement with viable and degenerate neutrophils, macrophages, sloughed nucleated squamous epithelial cells, necrotic debris, and numerous oval to round, 3-6 um diameter, pale-staining, thin-walled blastospores and blastoconidia arranged in short chains (pseudohyphae), as individual yeast, and as slender, 3-4 um wide, septate, parallel-walled non-branching hyphae. Within the mucosa there are numerous intraepidermal pustules which contain viable and degenerate neutrophils, yeast, and necrotic debris. The lamina propria is expanded by neutrophils, macrophages, and fewer lymphocytes and plasma cells which surround, separate, and cause disorganization, degeneration (vacuolated sarcoplasm with vesiculate nuclei), and necrosis (shrunken, angular, hypereosinophilic sarcoplasm with pyknotic nuclei) of smooth myocytes in the muscularis mucosa admixed with increased clear space and ectatic lymphatic vessels (edema).
Tongue: There is marked hyperplasia of mucosal epithelium characterized by deep rete ridge formation, acanthosis, increased intercellular clear space with prominent intercellular bridging (spongiosus), and increased intracellular clear space (hydropic degeneration). Within the superficial mucosa, in between epithelial cells, there are pockets of viable and degenerate neutrophils admixed with eosinophilic and karyorrhectic cellular debris (mucosal pustules). The overlying mucosa is eroded, with loss of the stratum corneum which is replaced by viable and degenerate neutrophils, sloughed nucleated squames (acantholytic keratinocytes), necrotic debris, and numerous oval to round, 3-6 um diameter, pale-staining, thin-walled blastospores and blastoconidia arranged in short chains (pseudohyphae), as individual yeast, and as slender, 3-4 um wide, septate, parallel-walled, non-branching hyphae. Adjacent epithelial cells are degenerate (swollen epithelial cells with vacuolated cytoplasm and vesiculate nucleus) or necrotic (shrunken epithelial cells with hypereosinophilic cytoplasm and pyknotic nucleus). Rarely, there is transmigration of neutrophils across the mucosa. Within the superficial submucosa there are numerous lymphocytes and plasma cells with fewer neutrophils admixed with increased clear space and ectatic lymphatic vessels (edema).
MORPHOLOGIC DIAGNOSIS: Esophagus and tongue: Esophagitis and glossitis, neutrophilic and histiocytic, diffuse, moderate with mucosal hyperplasia numerous fungal yeast, pseudohyphae, and hyphae (etiology consistent with Candida sp.), Owl monkey, non-human primate.
ETIOLOGIC DIAGNOSIS: Oral Candidiasis
CAUSE: Candida alibicans
- Members of the family Candida are ubiquitous, dimorphic, saprophytic fungi that normally inhabit the alimentary, upper respiratory and genital mucosa of mammals
- Most common species producing candidiasis are albicans and C. tropicalis; other species include C. glabrata, C. krusei, and C. parasillosis
- Candidiasis is mainly a disease of keratinized epithelium in young animals, especially pigs, calves, and foals
- In marine mammals disease is speculated to be associated with prolonged antibiotic use, immunosuppression, concurrent disease, and environmental stress/contamination
- Superficial (localized) candidiasis produces relatively mild lesions in skin and mucous membranes
- Non-human primates: lesions of the tongue, oral cavity (“thrush” or “moniliasis”), esophagus and intestine are most common
- Systemic (disseminated) candidiasis may involve any organ with the kidneys, heart valves, CNS and lungs most commonly affected
- All of the following can increase the risk of both localized and systemic candidiasis: immunosuppression, cytotoxic chemotherapy causing neutropenia, diabetes mellitus, long-term glucocorticoid therapy, prolonged use of broad-spectrum antibiotics (alters normal protective flora), or disruption of mucosal barriers (trauma, surgery, indwelling catheters, neoplasia)
- Candida produce a large number of functionally distinct adhesins that are important determinants of virulence; Candida yeast mainly bind mannose receptors, while Candida hyphae primarily bind complement receptor 3 (CR3) and the Fc-gamma receptor
- Adherence and persistence of many Candida species is facilitated by biofilm formation; biofilm formation also increases adherent Candida resistance to antifungal drugs
- Candida produce enzymes including aspartyl proteinases (degrades extracellular matrix proteins) and catalases (resists oxidative killing by phagocytic cells) as well as adenosine (blocks neutrophil oxygen radical production and degranulation
- Cell-mediated immunity appears to be an important limitation to the pathologic spread of Candida
- Accumulation of keratin in the upper digestive tract due to anorexia may also contribute to the extensiveness of lesions in all species by increasing the substrate available to the fungus
TYPICAL CLINICAL FINDINGS:
- Often nonspecific; related to the organ system(s) most severely affected
TYPICAL GROSS FINDINGS:
- Cutaneous/mucous membrane form (i.e. oral cavity, esophagus): White pseudomembranes that are peeled easily from the mucosal surface; reveal ulcerated or erythematous tissue underneath
- Systemic form: Multiple white foci in affected organs
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Pseudohyphae (chains of blastoconidia which are distinguished from true hyphae by constriction at points of attachment of the individual yeast); hyphae 3-4 um wide, parallel-walled, septate; and 2-6 um round to oval narrow-based budding yeast
- Systemic infections: Suppurative inflammation and necrosis; rarely granulomatous
- Inflammation may be minimal in severely immunosuppressed individuals
- Colonization of the keratinized stratified squamous epithelium of oral, crop and esophageal mucosa is typically limited to the stratum corneum but may extend into the superficial stratum spinosum
- Fibrinosuppurative membrane with necrotic debris, yeast, pseudohyphae, hyphae and sloughed epithelial cells often covers mucosal surface
ADDITIONAL DIAGNOSTIC TESTS:
- PAS, Gridley, and Gomori methenamine silver stains
- Culture results should be correlated with histology since albicans can be normal flora
- Geotrichum candidum: Yeast, pseudohyphae, and septate hyphae; may cause granulomatous inflammation
- Aspergillus sp: fumigatus most common; septate hyphae with dichotomous branching; conidiophores
- Zygomycetes: Usually nonseptate, branching hyphae; bulbous enlargements
- Loboa loboi: Granulomatous dermatitis in Atlantic bottlenose dolphins; yeast in branching chains
- Candida glabrata (previously Torulopsis glabrata): Do not form hyphae; 2-3um diameter yeast; now considered part of the Candida genus
- Histoplasma capsulatum: 2-4um yeast, intrahistiocytic
- Blastomyces dermatitidis: 7-17um yeast with single, broad-base budding
- Birds: common; infections in mouth, esophagus, crop, proventriculus; hyperkeratosis due to vitamin A deficiency or anorexia can help propagate infection
- Pigs (piglets): oral cavity – mycotic esophagitis (“thrush”), esophagus, and gastric squamous mucosa most often affected
- Ox: systemic infections; mastitis and abortion
- Calves: lesions are present in the ventral sac of the rumen, omasum, or reticulum following prolonged antibiotic therapy
- Horse: squamous epithelial ulceration typically adjacent to the margo plicatus (foal); valvular endocarditis (adult)
- Mice: gastritis reported in immunocompromised mice
- Rats: systemic infection of Sprague-Dawley rats is used to evaluate antifungal therapies
- Dog: mycotic stomatitis (“thrush”), peritonitis, cystitis, rare systemic disease or sepsis (usually in immunocompromised animals)
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