September 2024

D-F02

SIGNALMENT (JPC Accession #1142242): Cow

HISTORY: None

HISTOPATHOLOGIC DESCRIPTION: SLIDE A: Rumen: There is a transmural, wedge-shaped, focally extensive infarct comprising 30% of the tissue section. The infarct is characterized by a focally extensive area of loss of differential staining and retained tissue architecture (coagulative necrosis) bound transmurally by a 5 mm thick band of eosinophilic cellular and karyorrhectic debris (lytic necrosis) admixed with viable and necrotic neutrophils, macrophages, lymphocytes, and plasma cells that multifocally extends into and replaces the external muscularis layers and extends into the serosa. Multifocally within the infarcted and adjacent areas, the tunica media and tunica adventitia of blood vessels are expanded and effaced by lymphocytes, plasma cells, macrophages, fewer neutrophils, fibrin, edema, and karyorrhectic and cellular debris (necrotizing vasculitis). Affected vascular lumina are often occluded by fibrin with enmeshed previously described inflammatory cells and cellular and karyorrhectic debris (fibrin thrombi) admixed with and multiple fungal hyphae that extend transmurally through the vessel walls into the surrounding perivascular space. Fungal hyphae are 5-15 µm wide, pauci-septate, have non-parallel walls with bulbous dilatations, and exhibit non-dichotomous, irregular or right angle branching. The mucosal epithelium adjacent to the infarct is thickened up to 3 times normal with prominent anastomosing rete ridges (mucosal hyperplasia), intracellular and intercellular edema, multifocal erosions and ulceration, and intraepithelial aggregates of degenerate and viable neutrophils (abscesses). The lamina propria, submucosa, and serosa are markedly expanded by increased clear space and ectatic lymphatics (edema), previously described inflammatory cells, and fibrin. Mesothelial cells lining the serosa are multifocally hypertrophied (reactive).

SLIDE B: Gomori methenamine silver (GMS): Rumen: Multifocally throughout the tissue, often centered on vessels, there are GMS-positive fungal hyphae as previously described.

MORPHOLOGIC DIAGNOSIS: Rumen: Rumenitis, necrosuppurative, acute, focally extensive and transmural, severe, with infarction, necrotizing vasculitis, thrombosis, and numerous pauci-septate fungal hyphae, breed not specified, bovine.

ETIOLOGIC DIAGNOSIS: Ruminal mucormycosis (formerly zygomycosis)

CAUSE: Mucoromyces fungi (formerly Zygomyces)

CONDITION: Mycotic rumenitis

GENERAL DISCUSSION:

Implicated fungal organisms: Mucor, Rhizopus, Absidia, (phylum Mucoromycota, formerly obsolete phylum Zygomycota) with lesser frequency by Aspergillus and Mortierella spp
Ubiquitous saprophytic molds associated within water, soil, decaying matter, and substrates high in carbohydrates
Cause opportunistic disease in ruminants resulting in disseminated disease in immunocompromised or debilitated animals
Lesions result from submucosal venular thrombosis caused by fungal invasion
Occasional metastases to liver, and cause necrotizing thrombophlebitis
Organism is angioinvasive
Commonly affects the rumen, reticulum and omasum

PATHOGENESIS:

Fungi are common contaminants of feed and are normal GI inhabitants
Opportunistic infection secondary to mucosal damage caused by ruminal acidosis (grain overload), or may occur in the absence of ruminal acidosis, e.g. sepsis, prolonged antibiotic therapy, reflux of acidic abomasal contents, mucosal disease (bovine pestivirus, flavivirus), immunosuppression, recent parturition and ingestion of young grass
High carbohydrate diet (e.g. grain) > reduction in rumen pH > increase in ruminal volatile fatty acids > changes in ruminal microflora (increased Streptococcus bovis (produces lactic acid) followed by lactobacilli) > decreased rumen motility, movement of fluid into the rumen, and hypovolemia > ulceration of mucosa > invasion of submucosa and vessels by opportunistic fungi > thrombosis, infarction, necrosis

TYPICAL CLINICAL FINDINGS:

Anorexia, depression, rumen atony, foul-smelling feces
Increased heart and respiratory rates because of acidosis
Hypovolemia from movement of fluid from the circulation into the rumen due to change in osmotic pressure

TYPICAL GROSS FINDINGS:

Mycotic rumenitis is much more severe and extensive than necrobacillary rumenitis (caused by Fusobacterium necrophorum)
Well-circumscribed necrotic areas surrounded by zone of hyperemia that extends to the serosa in the rumen, reticulum, and omasum
+/- Fibrinohemorrhagic peritonitis that mats the omentum to the rumen
Extensive, well-demarcated infarcts; red to black, thickened, firm, and leathery
Liver: Small irregular tan areas of infarction bordered by a hyperemic margin

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Lesions are hemorrhagic and angiocentric: Necrotizing vasculitis, submucosal venular thrombosis, infarctions, and hemorrhagic necrosis
Diffuse pyogranulomatous inflammation (+/- transmural) with coagulative necrosis and multinucleated giant cells

Chronic cases: Granulomatous inflammation in the deep mucosa
Fibrinous exudate; varying leukocytic inflammation

Pauciseptate, thin-walled, 3-25 um wide fungal hyphae with non-parallel walls, non-dichotomous, irregular, often right angle, branching, and focal bulbous dilatations

Hyphae in necrotic/infarcted areas and within blood vessels (angiotropic)
Liver: Necrotizing thrombophlebitis of portal radicles with disseminated infections

These fungi can spread to the placenta hematogenously and cause mycotic placentitis resulting in abortion

DIAGNOSIS:

Histomorphology, silver stains, PAS
Fungal culture: Required for identification to genus and species
Immunohistochemistry, immunofluorescence, enzyme immunocomplex

DIFFERENTIAL DIAGNOSIS:

Fusobacterium necrophorum (necrobacillary rumenitis ): Usually superficial; affects papillated areas of ventral sac and occasionally ruminal pillars; less hemorrhagic

Mycotic rumenitis

Aspergillus fumigatus (phylum Ascomycota):

Hyphae stain poorly with hematoxylin and eosin and are 3-6 microns wide, septate, with parallel walls and acute angle, dichotomous branching
Reproduce asexually via conidia and sexually via an ascus (sac-like structure containing eight ascospores)

More common in abomasum
Angioinvasive
Candida albicans (Class Blastomycetes, Family Cryptococcaceae):

Masses of branching, septate hyphae, with pseudohyphae, and round to oval budding yeasts (blastospores)
Hyphae are 3-5 microns in diameter
Typically an infection of squamous epithelium in young animals (“thrush”)
Occasional opportunistic invader in aged animals
Imperfect fungus: Life cycle not completely defined; sexual stages unknown

COMPARATIVE PATHOLOGY:

Mucormycosis (formerly zygomycosis) in other species:

Dogs: Basidiobolus and Conidiobolus most common although rare: Ulcerative and granulomatous stomatitis, gastritis, and enteritis, lymphadenopathy with calcification, encephalitis, pneumonia, cutaneous nodules, cutaneous draining tracts
Horses: Lips and pharynx, nostrils, nasal mucosa
Birds: Trachea, bronchi, sinus (sinusitis), nasal cavity (rhinitis), and body cavity; affinity to localize within blood vessels and the heart; pulmonary granuloma and pneumonia; proventriculitis and ventriculitis with erosion and ulceration; hyphae non-septate or rarely septate with non-dichotomous branching
Bison: Severe, diffuse fibrinous peritonitis; large area of infarction and hemorrhages on the omasum, abomasum, and reticulum
NHPs: Gastric and intestinal lesions most common; angioinvasion with thrombosis Platypus: Mucor amphibiorum causes granulomatous dermatitis with significant mortality and morbidity; secondary to skin wounds/ trauma it can extend into underlying muscule and internal organs (primarily lungs)
Cetaceans: Mucor, Rhizopus, Rhizomucor, Absidia, Aphophysomyces and Saksenaea associated with vascular infection (necrosis, vasculitis, hemorrhage, thromboembolism, ischemia, infarction), dermatitis, cellulitis or myositis.
Ostrich chicks: Proventriculus and ventriculus mucosal erosion and ulceration, subserosal edema and hemorrhage, with intralesional fungus; ventriculus may have characteristic thick layer of mucosal mucus due to mucous cell hyperplasia
Frogs/toads: Mucor amphibiorum causes disseminated mycosis forming a unique nonhyphal spherule; grossly pale green to yellow nodules on serosal surfaces and in parenchyma of liver, spleen and kidney; cutaneous papules +/- ulceration

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