JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
August 2021
D-F02

 

 

SLIDE A:  SIGNALMENT (JPC Accession #1142242):  Cow

 

HISTORY:  None

 

HISTOPATHOLOGIC DESCRIPTION:  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 um 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:  Mucormyces fungi (formerly Zygomyces)

 

CONDITION:  Mycotic rumenitis

 

GENERAL DISCUSSION: 

• Implicated fungal organisms: Mucor, Rhizopus, Absidia, (phylum Mucormycota, 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 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

 

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 abomasums
  • 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: Ulcerative and granulomatous stomatitis, gastritis, and enteritis, lymphadenopathy with calcification, encephalitis, pneumonia, cutaneous nodules        
• Horses: Lips and pharynx, nostrils, nasal mucosa
• Bison: Severe, diffuse fibrinous peritonitis; large area of infarction and hemorrhages on the omasum, abomasum, and reticulum

 

REFERENCES:

1. Chandler FW, Kaplan W, Ajello L. Color Atlas and Text of the Histopathology of Mycotic Diseases. Lochem, NL: Wolfe Medical Publications; 1980: 122-126, 294-300.
2. Dyer NW, Newell TK. Mycotic Rumenitis in American Bison (Bison bison). J Vet Diagn Invest. 2002; 14(5):414-416.
3. Gelberg HB. Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:393-394.
4. Jang SS, Walker RL. Fungal diseases. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 4th ed. St. Louis, MO: Elsevier Saunders; 2012: 683-684.
5. Jensen HE, Olsen SN, Aalbaek B. Gastrointestinal aspergillosis and zygomycosis of Cattle. Vet Pathol. 1994; 31:28-36.
6. Jones EM, Gasper DJ, Mitchell E. Chapter 5: Bovidae, Antilocapridae, Giraffidae, Tragulidae, Hippopotamidae. In: Terio KA, McAloose D, St. Leger J, ed. Pathology of Wildlife and Zoo Animals, Cambridge, MA Academic Press; 2018: 119.
7. Songer JG, Post KW. Veterinary Microbiology, Bacterial and Fungal Agents of Animal Disease. St. Louis, MO: Elsevier Saunders; 2005: 398-401.
8. Uzal FA, Platter BL, Hostetter JM. Alimentary System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. St. Louis, MO: Elsevier; 2016: 40-43.
9. Vermunt JJ, West DM. Fusobacterium necrophorum, Dichelobacter (Bacteroides) nodosus and Bacteroides infections. In: Coetzer JAW, Tustin RC, eds. Infectious Diseases of Livestock. 3rd ed. Oxford, UK: Oxford University Press; 2004: 1738-1741.

 

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