AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2017

N-F04

 

Signalment (JPC #2023496):  6-year-old female African elephant (Loxodonta africana)

 

HISTORY:  Located in the left superior temporal lobe was a focal, circumscribed (2.3 cm), grayish‑white, firm mass.

 

HISTOPATHOLOGIC DESCRIPTION: Brain, cerebrum: Effacing 70% of the tissue, affecting both gray and white matter, and compressing the adjacent neuropil is a 1.5 cm diameter granuloma composed of a large central area of necrotic debris (necrosis) centered on small, primarily extracellular clusters of brown pigmented yeast, pseudohyphae and hyphae, further surrounded by low numbers of epithelioid macrophages and rare multinucleated giant cells. At the periphery, there are multiple foci of deeply basophilic mineral admixed with foamy gitter cells, few remaining gliovascular strands, and low numbers of multinucleate giant cells that occasionally contain intracytoplasmic fungal hyphae. Yeasts are round to oval, 8‑10 um in diameter, and occasionally form chains (pseudohyphae). Hyphae are septate, with parallel walls that are 4-6um in width and with occasional bulbous dilatations up to 25um in diameter. The granuloma is surrounded by a 400 um wide band of fibrous connective tissue that is infiltrated by few lymphocytes, plasma cells, and neutrophils. These inflammatory cells also form multifocal perivascular cuffs around small vessels lined by hypertrophic (reactive) endothelial cells and minimally infiltrate the meninges. There is multifocal mild gliosis in the adjacent, spongiotic neuropil including few gemistocytes and rod-shaped microglia.

 

MORPHOLOGIC DIAGNOSIS: Cerebrum: Granuloma, focal, with extracellular and rare intrahistiocytic pigmented fungal yeast, pseudohyphae and hyphae, African elephant (Loxodonta africana), proboscid.

 

ETIOLOGIC DIAGNOSIS: Cerebral phaeohyphomycosis

 

CAUSE:Presumed Cladosporium sp.

 

GENERAL DISCUSSION:

·       Phaeohyphomycosis: Infection with dematiaceous (pigmented) fungi

·       Dematiaceous fungi are widespread saprophytes and cause opportunistic infections

·       Cladophialophora bantianum and Cladosporium bantianum are neurotropicand the most common cause of cerebral phaeohyphomycosis

 

PATHOGENESIS:

·       Two forms of phaeohyphomycosis are described:

·       Cutaneous (usually subcuticular):  Colonization of epidermis, hair follicles and subcutis following traumatic implantation

·       Systemic infection: 

·       Hypothesized as inhalation leading to pulmonary infection followed by hematogenous spread, however primary pulmonary infection not always identified

·       Hematogenous spread to CNS from fungal otitis has been documented

·       Cell mediated immunity is necessary to prevent infection; immunosuppression is  common in affected animals

·       The mechanism of neurotropism is unknown

·       Melanin synthesis in cell walls thought to be main virulence factor by blocking effects of hydrolytic enzymes and scavenging free radicals released by phagocytes

 

TYPICAL CLINICAL FINDINGS:

·       Variable or no CNS signs including proprioceptive deficits, nystagmus, lethargy, ataxia, paralysis, weakness, neck pain

 

TYPICAL GROSS FINDINGS:

·       Focal or multifocal; variably discrete areas of malacia to well defined abscesses

·       Meninges may be thickened and opaque

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·       Pigmented branching, septate, parallel walled hyphae, pseudohyphae, and yeast‑like organisms; extracellular and intracellular

·       Hyphae form dilated, round, thick walled structures resembling chlamydospores or chlamydoconidium

·       Hyphae are septate, irregular in width (2-8 um), with non-parallel pigmented walls and random dilated segments up to 25 um in diameter, resembling chlamydospores

·       Discrete abscesses with thick fibrous encapsulation to less discrete pyogranulomatous inflammation

·       Epithelioid and multinucleate macrophages.

·       Suppurative meningitis

·       Vascular invasion with thrombosis possible

 

ADDITIONAL DIAGNOSTIC TESTS:

·       Special fungal stains (eg. GMS, Gridley's) are not normally necessary

·       Fontana-Masson method will highlight sparsely pigmented fungi

·       Culture required for a specific diagnosis

 

DIFFERENTIAL DIAGNOSIS:

Cerebral mycoses:

·       Cryptococcus neoformans

·       Common saprophyte, often systemic infection

·       Grossly gelatinous foci in the brain

·       Large (up to 20 um); thick carminophilic capsule

·       Blastomyces dermatitidis,: Yeasts with broad based budding

·       Chromoblastomycosis:  Pigmented, without hyphae

·       Aspergillus sp., Mucor sp., Candida sp.:  Hyphae are not pigmented

 

COMPARATIVE PATHOLOGY:

·       Reported in horses, cattle, dogs, birds, and cats

·       Chickens and turkeys:  Epizootic encephalitis caused by Ochroconis gallopavum (a dematiaceous fungus)

·       Associated with ossification of the skull and cervical vertebrae in a shark

·       Reported to cause disseminated fungal infection in weedy and leafy seadragons

 

References:

1.      Bonar CJ, Garner MM, et al. Pathologic findings in weedy (Phyllopteryx taeniolatus) and leafy (Phycodurus eques) seadragons. Vet Pathol. 2013; 50(3):368-376.

2.      Bouljihad M, Lindeman CJ, Hayden DW. Pyogranulomatous meningoencephalitis associated with dematiaceous fungal (Cladophialophora bantiana) infection in a domestic cat. J Vet Diagn Invest. 2002; 14(1):70-72.

3.      Chandler F. Pathologic Diagnosis of Fungal Infections.  Chicago, IL: American Society of Clinical Pathologists Press; 1987:239-247.

4.      Dillehay D, Ribas J, Newton J, Kwapien R. Cerebral phaeohyphomycosis in two dogs and a cat.  Vet Pathol. 1987; 24:192-194.

5.      Eliesi L, Balandraud V, Boulouha L, Crespeau F, Guillot J. Fatal systemic phaeohyphomycosis in a cat due to Cladophialophora bantiana. J Vet Med A Physiol Pathol Clin Med. 2003; 50(1):50-53.

6.      Erlacher-Reid C, Nollens HH, Schmitt TL, St. Leger J, Sunico S. Phaeohyphomycosis associated with ossification of the skull and cervical vertebrae in a swell shark (Cephaloscyllium ventriosum). J Zoo Wildl Med. 2016; 47(4):1081-1085.

7.      Frank C, Vemulapalli R, Lin T. Cerebral phaeohyphomycosis due to Cladophialophora bantiana in a Huacaya alpaca (Vicugna pacos). J Comp Pathol. 2011; 145(4):410-413.

8.      Giri DK, Sims WP, Sura R, Cooper JJ, Gavrilov BK, Mansell J. Cerebral and renal phaeohyphomycosis in a dog infected with Bipolaris species. Vet Pathol. 2011; 48(3):754-757.

9.      Herraez P, Rees C, Dunstan R. Invasive phaeohyphomycosis caused by Curvularia species in a dog. Vet Pathol. 2001; 38:456-459.

10.   Lapointe J, Higgins R, Sturges B. Phaeohyphomycotic ependymitis in a cat. J Vet Diagn Invest. 1998; 10:202-204.

11.   Mauldin E, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA:Elsevier; 2016:654-655.

12.   Mariani CL, Platt SR, Scase TJ, Howerth EW, Chrisman CL, Clemmons RM. Cerebral phaeohyphomycosis caused by Cladosporium sp. in two domestic shorthair cats. J Am Anim Hosp Assoc. 2000; 38(3):225-230.

13.   Perpinan D, Blas-Machado U, Sanchez S, Miller DL. Concurrent phaeohyphomycosis and ranavirus infection in an eastern box turtle (Terrapene carolina) in Athens, Georgia, USA. J Wildl Dis. 2016; 52(3):742-745.

14.   Summer B, Cummings J, de Lahunta A. Veterinary Neuropathology. St. Louis, MO: Mosby; 1995:151-155.



 





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