AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

August 2019

I-F08 (NP)

 

Signalment (JPC #1665005): Monkey

 

HISTORY: None

 

HISTOPATHOLOGIC DESCRIPTION: Slide A: Mucous membrane (site not specified): Markedly expanding the submucosa are multifocal to coalescing nodular cellular infiltrates predominately composed of macrophages admixed with moderate numbers of non-degenerate and degenerate neutrophils, and fewer eosinophils, lymphocytes, plasma cells, and multinucleated giant cells (Langhans and foreign-body type) and variable amounts of eosinophilic cellular and karyorrhectic debris (necrosis), fibrin, and hemorrhage. Occasionally these aggregates have central areas of necrosis bordered by macrophages and few neutrophils, further surrounded by collagen and reactive fibroblasts (granulomas). Scattered throughout the inflammation and within multinucleated giant cells are numerous 4-8um diameter round yeast with 1um thin eosinophilic walls and clear centers that are surrounded by clear space that is up to 10um thick (capsule). Scattered similar inflammatory cells extend multifocally into the adjacent skeletal muscle, disrupting and separating myofibers. The superficial submucosa is expanded by fibrin, edema, few plasma cells, lymphocytes, and rare neutrophils.

 

Slide B: Mucicarmine stain: The capsule is 3-8um thick and bright red (carminophilic). Fungal organisms are 4-8um in diameter, occasionally clustered, and frequently bud with a narrow base. The organisms are surrounded by a 10-15um thick, clear space (shrinkage artifact) with short radiating carminophilic spines extending from the capsule.

 

MORPHOLOGIC DIAGNOSIS: Mucous membrane (site not specified): Cellulitis, pyogranulomatous, multifocal to coalescing, marked, with numerous encapsulated yeast, etiology consistent with Cryptococcus spp., monkey (species not specified), non-human primate.

 

ETIOLOGIC DIAGNOSIS: Mucosal cryptococcosis

 

CAUSE: Cryptococcus neoformans

 

SYNONYM: European blastomycosis; torulosis

 

GENERAL DISCUSSION:

·      Causes subacute or chronic mycotic infection in humans and a wide variety of animals and has a predilection for the respiratory system (especially nasal region) and central nervous system; cutaneous and ocular lesions are seen less frequently

·      Organism is dimorphic, saprophytic, yeast-like fungus that is 3.5-7um in diameter with a large 1-30um diameter heteropolysaccharide capsule; reproduces by single, narrow-based budding

·      One of the few systemic mycoses that affects cats more commonly than dogs

·      Pigeons thought to be the most important vector; the pigeon’s high body temperature is thought to protect it from pathogenic infection

·      Organism is not contagious and primarily infects animals that are immunocompromised, stressed, or treated for prolonged periods with corticosteroids

·      Inflammation is mild compared to the number of organisms observed within lesions

·      Inflammation can be severe in cutaneous capsule-deficient strains

 

PATHOGENESIS:

·      Opportunistic infection usually via inhalation

·      Organisms are unencapsulated in the environment, increasing the chances of aerosolization; once in the respiratory system, they regain their capsule

·      Can disseminate hematogenously or via lymphatics

·      Can extend locally from the nasal cavity to the CNS

·      Virulence factors

1. Polysaccharide capsule - prevents phagocytosis by macrophages, inhibits leukocyte migration, and inhibits recruitment of inflammatory cells

2. Melanin – antioxidant properties

 

TYPICAL CLINICAL FINDINGS:

·      Majority of clinical signs are attributable to infection of the primary organ (i.e. lung, nasal cavity, skin, ocular, or CNS)

 

TYPICAL GROSS FINDINGS: (lesions in the skin)

·      Well-circumscribed, firm small nodules which tend to ulcerate

·      Draining tracts may be present which exude mucoid to serous exudate that contains organisms

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·      Foamy (“soap-bubble”) appearance due to unstained capsules of organisms

·      Pleomorphic, round or oval, thin‑walled cells (3.5-7um diameter) surrounded by a thick heteropolysaccharide capsule (1-30um diameter) that forms a clear or refractile halo

·      Reproduce by narrow-based budding

·      Inflammation is usually scant to absent in the skin

·      If present, inflammation consists of macrophages with engulfed organisms and variable numbers of neutrophils

·      Marked pyogranulomatous and eosinophilic dermatitis is associated with capsule-deficient C. neoformans

 

 

ULTRASTRUCTURAL FINDINGS:

·      Capsule is formed of filaments which are anchored in the cell wall and radiate peripherally

·      Microbody is found in cytoplasm – a modified peroxisome that is involved in metabolism of xanthine and urate; may underlie propensity to live in urate-rich bird feces

 

ADDITIONAL DIAGNOSTIC TESTS:

·      Cytology of aspirate or direct smear; Negative staining of wide capsular zone by India ink

·      Capsule stains with mucicarmine, PAS, GMS and Fontana-Masson; the clear halo that remains around the mucicarmine-stained organism is due to shrinkage of the capsule during fixation

·      Culture: May take up to 6 weeks for positive culture

·      Serologic tests: Latex agglutination procedure to identify capsular antigen

 

DIFFERENTIAL DIAGNOSIS:

For microscopic findings:

·      Poorly encapsulated C. neoformans is difficult to differentiate from other unencapsulated fungi

·      Blastomyces dermatitidis - lacks the wide capsule and exhibits broad-based budding

·      Histoplasma capsulatum var. capsulatum - smaller (2-5um); usually within macrophages

·      Coccidioides immitis - much larger (5-50um); reproduces by endosporulation rather than budding

·      Candida albicans - often forms yeast, hyphae, and pseudohyphae in tissue

·      Lacazia (Loboa) loboi – often forms chains of yeast in tissue

·      Sporothrix schenckii – smaller (3-8um); more pleomorphic, often cigar-shaped

 

COMPARATIVE PATHOLOGY:

·      Most species acquire the respiratory or CNS form

 

Cats:

·      Most common systemic fungal infection in the cat; Siamese cats may have an increased risk of infection

·      Upper nasal cavity is typically initial site of infection; also have CNS (extension through the cribriform plate), ocular, and cutaneous involvement; skin lesions occur in 40-50% of cases and are often on the face, pinnae, and paws

 

Dogs:

·      Young, large breed dogs are overrepresented, disseminated form more common; may occur in immunocompetent hosts, skin lesions may occur on the nose, lips, tongue, and nail beds, one recent report of pyelonephritis

·      Bovine: Associated with mastitis

·      Llama: Report of infection in brain, spinal cord, lung, and kidney

·      Elk: Report of meningoencephalitis and pneumonia

·      Humans: Occurs in immunocompromised people, primarily CNS

 

REFERENCES:

1.    Craig LE, Dittmer KE, Thompson, KG. Bones and Joints. In: Maxie MG ed. Jubb, Kennedy,and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier; 2016:104.

2.    Gross TL, Ihrke PJ, Walder EJ, Affolter VK. In: Skin diseases of the dog and cat. 2nd ed. St Louis, MO: Blackwell publishing; 2005:291.

3.    Myers A, Meason-Smith C, et al. Atypical cutaneous cryptococcosis in four cats in the USA. Vet Dermatol. 2017; 28(4):405-e97.

4.    Sykes JE, Malik R. Cryptococcosis. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 4th ed. St. Louis, MO: Elsevier Saunders; 2012:621-634

5.    Hargis AM, Myers S. The integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:1084.

6.    Miller, Jr. WH, Griffin CE, Campbell KL. In: Muller and Kirk’s Small Animal Dermatology. 7th ed. St. Louis, MO: Elsevier; 2013: 262-264.


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