JPC SYSTEMIC PATHOLOGY
Signalment (JPC 21474-5/6): 2-year-old dog
HISTORY: This dog from Florida had an expanding 3 cm circular indurated granuloma with numerous sinuses and fistulas in the skin over the right flank.
HISTOPATHOLOGIC DESCRIPTION: SLIDE A: Haired skin: Affecting up to 75% of the deep dermis and subcutis, extending into the panniculus and separating and surrounding skeletal myofibers are coalescing 0.5-2mm inflammatory nodules centered on faint negative images of fungal hyphae embedded in eosinophilic cellular and karyorrhectic debris (lytic necrosis). Necrotic foci and fungal hyphae are surrounded by numerous epithelioid macrophages, lymphocytes, plasma cells, and few neutrophils, with occasional multinucleated giant cells (foreign body and Langhans' type), admixed with fibroblasts and scant fibrous connective tissue. Inflammation extends into the adjacent adipose tissue and skeletal muscle. Remaining skeletal myocytes are often shrunken with fragmented hypereosinophilic sarcoplasm and nuclear pyknosis (necrosis), or pale, swollen and vacuolated (degeneration). Multifocally, scattered macrophages contain brown, intracytoplasmic pigment (hemosiderin). Diffusely, there is mild orthokeratotic hyperkeratosis.
Slide B: Gomori methenamine silver (GMS): Within the pyogranulomas are many, argyrophilic hyphae and hyphal fragments. Hyphae are occasionally septate, 4-15um in width with non-dichotomous branching and thin, non-parallel walls.
MORPHOLOGIC DIAGNOSIS: Haired skin: Dermatitis and panniculitis, nodular, granulomatous, multifocal and coalescing, marked, with numerous fungal hyphae, breed not specified, canine.
ETIOLOGIC DIAGNOSIS: Cutaneous zygomycosis
- Rare disease in dogs, cats, horses, llamas, sheep, and pigs
- Class Zygomycetes has two orders:
- Order Mucorales:
- Systemic disease called “mucormycosis”
- Genera: Absidia, Mucor, Rhizopus, Rhizomucor, Mortierella
- Order Entomophthorales
- Subcutaneous disease called “entomophthoromycosis”
- Genera: Basidiobolus, Conidiobolus
- Non-contagious (environment is the source), ubiquitous, saprophytic fungi
- Three syndromes have been described:
- Cutaneous/subcutaneous (most frequently in horses) – Basidiobolus haptosporus (horse) & Conidiobolus coronatus (dogs) most common
- Immune compromise usually not a feature as it is in humans, rather exposure to large numbers of organisms or implantation via penetrating injury
- Gains entry through cutaneous wounds, oral cavity, respiratory tract
- Systemic dissemination through angioinvasion by hyphae; common with Mucorales, but uncommon feature of Entomophthorales
TYPICAL CLINICAL FINDINGS:
- Pruritis is a common feature
- Chronic, rapidly progressive
TYPICAL GROSS FINDINGS:
- Skin lesion on lateral head, neck, trunk: Nodular, ulcerated, draining, with small yellow/white gritty masses (kunkers, leeches)
- Can reach 30 cm in diameter
- Surface is alopecic, scarred and ulcerated
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Necrotic core surrounded by a zone of eosinophils, neutrophils, epithelioid macrophages, and multinucleated giant cells are separated by fibrovascular connective tissue.
- Broad (5-20.5um), sparsely septate hyphae with non-dichotamous branching and non-parallel walls that stain poorly with routine (H&E) stains
- Folded, twisted, or compressed hyphae may be seen
- Some hyphae are surrounded by eosinophilic granular material or “eosinophilic halo” - (Splendore-Hoeppli phenomenon)
- Will see fungal hyphae within vessel walls commonly with Mucorales, but not with Entomophthorales
ADDITIONAL DIAGNOSTIC TESTS:
- Genus and species can only be diagnosed by culture
- Good staining with GMS, poor staining with PAS
- Need immunohistochemistry, culture or PCR to differentiate from pythiosis
Gross (cutaneous granulomas):
- Pythiosis–skin lesions most common in horses andgenerally located on lower limbs and ventrum with larger, coral shaped kunkers; skin lesions less common in dogs
- Bacterial granulomas
- Foreign-body granulomas
- Subcutaneous mycoses, algae and their infective agents include the following:
- Pythium - Lesions are very similar to zygomycosis, but hyphae are narrower (2-6um) and thicker walled; need culture to definitively differentiate
- Lagenidium – Reported only in dogs, more clinically aggressive than pythiosis, tends to go to distant visceral sites, hyphae stain with H&E
- Aspergillus - Parallel walls, with dichotomous branching of septate hyphae
- Candida - Parallel septate hyphae along with yeast-like cells and pseudohyphae
- Phaeohyphomycosis - Pigmented or dematiaceous fungi
- Eumycotic mycetoma - Presence of macroscopic granules in the exudates
- Prototheca wickerhamii - Usually a systemic disease in dogs and cats
- Sporothrix schenckii - Oval or cigar shaped yeasts
- Rhinosporidium seeberi - Large (100‑300 um) endosporulating sporangia
- Coccidioides immitis - Zygomycetes have been confused with this organism when there are transected hyphae-like spherules present in section
- Horse: Basidiobolus haptosporus ‑ subcutaneous swellings of lateral head, chest, and neck
- Non‑human primate and horse: Conidiobolus coronatus – subcutaneous nasofacial swelling
- Sheep: Conidiobolus incongruus ‑ rhinocerebral and nasal zygomycosis, loss of condition and death within 7-10 days
- Bovine: Mucormycosis (Mucor, Rhizopus, Absidia) ruminal ulceration and mastitis secondary to grain overload; Zygomycetes cause abortions, second only to Aspergillus fumigatus; a differential diagnosis for granulomatous lymphadenitis in feedlot steers
- Basidiobolus has been associated with the digestive tracts of a wide variety of amphibians and reptiles
- Porpoise: Mucormycosis (Neophocaena spp) systemically with secondary granulomatous pericarditis
- Canaries: ramosissimus associated with feather loss in canaries
- Deer: Conidiobolus incongruous associated with systemic infection and osteopathy
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