AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2020

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 neuroparenchyma is a 1.5 cm diameter granuloma composed of a large central area of eosinophilic cellular and karyorrhectic debris (necrotic debris) interspersed with 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 of the granuloma, internal to a thick, 400um wide band of dense, mature fibrous connective tissue, there are multiple foci of deeply basophilic mineral admixed with epithelioid macrophages, few 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 4-6um walls, with occasional bulbous dilatations up to 25um in diameter. The fibrous capsule and surrounding neuroparenchyma are multifocally infiltrated by few lymphocytes, plasma cells, and neutrophils, which multifocally form perivascular cuffs around small vessels and minimally infiltrate the meninges. There is multifocal mild gliosis in the adjacent, spongiotic neuropil including few gemistocytes and rod-shaped microglia (rod cells).

 

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 (chromomycosis)

 

CAUSE: Presumed Cladosporium sp.

 

GENERAL DISCUSSION:

·       Phaeohyphomycosis: Uncommon; infection with dematiaceous (pigmented) fungi

·       Vs. hyalohyphomycosis (paecilomycosis): infection with non-pigmented, saprophytic fungi

·       Dematiaceous fungi are widespread saprophytes and cause opportunistic infections; species include Alternaria, Bipolaris, Cladosporium, Curvularia, Exophila, Phialophora, Wangiella, Drechslera

·      Cladophialophora is the most common cause of cerebral phaeohyphomycosis in dogs and cats (Grooters, Infectious Diseases of the Dog and Cat, 2012)

·      Reported most commonly in horses, cattle, dogs, birds, and cats; German shepherd dogs may be predisposed

 

PATHOGENESIS:

·      Two forms of phaeohyphomycosis are described:

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

·      Systemic infection:

·      Hypothesized as inhalationàpulmonary infectionàhematogenous 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, 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 microabscesses

·      Pigmentation may be grossly visible

·      Meninges may be thickened and opaque

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

·      Discrete abscesses with thick fibrous encapsulation

·      Hyphae are septate, 2-6um (often variable in width), with variably present branching, and are often individualized or in small aggregates scattered throughout lesion; pigmentation may not be apparent in tissue sections

·      Necrosis may be extensive

·      Vascular invasion with thrombosis possible

·      Skin lesions contain variably discrete abscesses to less discrete pyogranulomatous dermatitis and panniculitis

 

ADDITIONAL DIAGNOSTIC TESTS:

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

·      Fontana-Masson method will highlight the pigment of sparsely pigmented fungi (such as Alternaria spp.)

·      Culture or molecular diagnostics is required for a specific fungal species diagnosis due to similar morphologic appearance between etiologic agents

DIFFERENTIAL DIAGNOSIS:

Cerebral mycoses:

·      Other pigmented lesions:

·      Chromoblastomycosis: Pigmented fungi, histologically lacks presence of hyphae; bulbous forms termed “sclerotic bodies”

·      Melanocytic neoplasms

·      Other fungal encephalidities:

·      Chromoblastomycosis: Pigmented fungi, histologically lacks presence of hyphae; bulbous forms termed “sclerotic bodies

·      Cryptococcus neoformans (N-F02)

·      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

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

·      Fungal skin lesions:

·      Dog, case report: Cutaneous-lymphatic form of sporotrichosis

·      Eumycotic mycetomas (eumycetoma): discrete organized (often) extracellular granules (fungi) with Splendore-Hoeppli reaction forming “tissue grains”

 

COMPARATIVE PATHOLOGY:

·      Dogs: Often multiple lesions; ulceration, draining nodules, and/or plaques on paws and legs

·      Cats: Lesions most often single, involving the nose or pinnae (face), and paws; ulceration, draining tracts

·      Horses: Lesions often multifocal, though can be generalized

·      Cattle: Multiple ulcerate cutaneous nodules; may involve nasal mucosa

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

·      Zoo/exotic species (Pathology of Wildlife and Zoo Animals, 2018)

·      Amphibians: Pigmented fungi, including Cladosporium, Philalophora, and Fonsecaea species, among others, cause chromoblastomycosis and phaeohyphomycosis, more often in captive amphibians

·      Chelonia: Phaeohyphomycosis infections associated with granulomatous to ulcerative skin lesions on the feet and tail (box turtles), oral granuloma (radiated tortoise), deep ulcerative shell lesions (Aldabra tortoise), and unilateral ocular infection and systemic disease (Galapagos tortoise)

·      Bony fish species (Osteichthyes): Phaeohyphomycosis lesions may be cutaneous, subcutaneous, or systemic

·      Weedy and leafy seadragons: Disseminated phaeohyphomycosis (Exophiala angulospora, E. aquamarina) infection characterized by systemic necrotizing lesions, angioinvasion, and vascular necrosis, with/without cutaneous ulcers

·      Atlantic salmon: Infection with E. pisciphila, with hyphal invasion of the cranial structures, semicircular canals and lateral line, with granulomatous inflammation

·      Phomamycosis causes phaehypomycosis of hatchery-reared fish, especially salmonids in intensive aquaculture

·      Grevy’s zebra: Focal pyogranulomatous pneumonia, myocarditis and pericardial effusion; yeast forms found in the heart

·      Shark, case report: Associated with ossification of the skull and cervical vertebrae (Erlacher-Reid, Jour Zoo Wildl Med 2016)

 

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.

  1. Duncan M. Perissodactyls. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 449.

3.    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). Jour Zoo Wildl Med. 2016;47(4): 1081-1085.

4.    Frasca, Jr. S, Wolf JC, Kinsel MJ, Camus AC, Lombardini ED. Osteichthyes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 973-975.

5.    Grooters AM, Foil CS. Miscellaneous fungal infections. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 4th ed. St. Louis, MO: Elsevier-Saunders; 2012: 685-687.

6.    Hargis AM, Myers S. The integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed., St. Louis, MO: Elsevier; 2017: 1083.

7.    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: 653-655.

8.    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. Jour Wildl Dis. 2016;52(3): 742-745.

  1. Pessier AP. Amphibia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 932-933.
  2. Rodriguez CE, Henao Duque AMH, Steinberg J, Woodburn DB. Chelonia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 839.


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