JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
August 2021
D-F05 (NP)

 

SIGNALMENT (JPC Accession #3165184):  A 4-year-old male owl monkey (Aotus sp.)

 

HISTORY:  This monkey had experienced weight loss and anemia of an 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 diffuse marked hyperplasia of the mucosal epithelium characterized by deep rete ridge formation and acanthosis, and there is increased intercellular clear space with prominent intercellular bridging (spongiosis) and intracellular edema (hydropic degeneration).  There are frequent areas of erosion and rare ulceration with replacement by, as well as frequent intramucosal pustules filled with, viable and necrotic neutrophils, macrophages, sloughed nucleated squamous epithelial cells, necrotic debris, and numerous fungi of varying life stages.  There are oval to round, 3-6 um diameter, pale-staining, thin-walled blastospores and blastoconidia arranged either in short chains (pseudohyphae), individual yeast, and slender, 3-4 um wide, septate, parallel-walled, non-branching hyphae. The lamina propria and submucosa are expanded by neutrophils, macrophages, and fewer lymphocytes and plasma cells.  Within the muscularis mucosa, these inflammatory cells which surround, and separate smooth muscle myocyte that are variably disorganized, degenerate (vacuolated sarcoplasm with vesiculate nuclei), and necrotic (shrunken, angular, hypereosinophilic sarcoplasm with pyknotic nuclei). There is mildly increased clear space and ectatic lymphatic vessels (edema) within the lamina propria and submucosa.   

 

Tongue:  There is diffuse marked hyperplasia of the mucosal epithelium characterized by deep rete ridge formation and acanthosis, and there is increased intercellular clear space with prominent intercellular bridging (spongiosis), and intracellular edema (hydropic degeneration).  The superficial mucosa contains pockets of viable and degenerate neutrophils admixed with eosinophilic and karyorrhectic cellular debris (intramucosal pustules).  The overlying mucosa is eroded and replaced by viable and necrotic neutrophils, sloughed nucleated 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 erosive, multifocal to coalescing, moderate, with mucosal hyperplasia and numerous yeast, pseudohyphae, and fungal hyphae, etiology consistent with Candida sp., Owl monkey, non-human primate.

 

ETIOLOGIC DIAGNOSIS:  Oral Candidiasis

 

CAUSE:  Candida alibicans

 

CONDITION:  “Thrush”

 

GENERAL DISCUSSION: 

• Candida are ubiquitous, dimorphic, saprophytic fungi that normally inhabit the alimentary, upper respiratory, and genital mucosa of mammals
• Most common species associated with 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, the disease is speculated to be associated with prolonged antibiotic use, immunosuppression, concurrent disease, and environmental stress/contamination

 

PATHOGENESIS: 

• 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, but most commonly affect the kidneys, heart valves, CNS, and lungs
• 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 the 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 the 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

 

DIFFERENTIAL DIAGNOSIS: 

• Geotrichum candidum: Yeast, pseudohyphae, and septate hyphae; may cause granulomatous inflammation
• Aspergillus sp: fumigatus most common; parallel, septate hyphae with dichotomous acute angle branching; conidiophores at air interfaces
• Zygomycetes: Usually nonseptate, branching hyphae; bulbous enlargements
• Paracoccidioides brasiliensis (previously named Lacazia loboi and 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

 

COMPARATIVE PATHOLOGY: 

• Birds: common; infections in the 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 the gastric squamous mucosa (pars esophagea) are 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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