JPC SYSTEMIC PATHOLOGY
REPRODUCTIVE SYSTEM
January 2022
R-F01

Signalment (JPC# 1421031):  Bovine fetus

HISTORY:  None

SLIDE A: HISTOPATHOLOGIC DESCRIPTION:  Placenta, chorioallantois and yolk sac:  Diffusely, there is loss of the chorionic villar architecture of the cotyledon and thickening of both the cotyledonary and intercotyledonary chorioallantois up to 1mm.  Within the cotyledon, the chorionic villar epithelium along the disrupted villi is replaced with abundant eosinophilic cellular and basophilic karyorrhectic debris (necrosis) admixed with fewer identifiable sloughed trophoblasts, occasional scattered viable and necrotic neutrophils and macrophages, hemorrhage, fibrin, several free and intracytoplasmic 1-2um diameter basophilic coccobacilli, and few negative staining fungal hyphae.  The fungal hyphae are 2-4um wide, septate, parallel walled, and exhibit dichotomous branching.  The stroma of the cotyledonary and intercotyledonary chorioallantois as well as the yolk sac is expanded by moderate numbers of macrophages, fewer neutrophils and lymphocytes, and scattered eosinophilic cellular and basophilic karyorrhectic debris, multifocal hemorrhage, fibrin, edema, and rare foci of angular basophilic material (mineral).  Multifocally, the tunica intima and tunica media of numerous blood vessels within the chorioallantoic stroma are disrupted and contain abundant karyorrhectic debris with few invading fungal hyphae as previously described (necrotizing vasculitis; angioinvasion).  The fungal hyphae are also present within cellular debris adhered to the allantoic membrane and along the margin of the parietal yolk sac.

Haired skin:  There is multifocal mild epidermal hyperplasia (acanthosis), spongiosis, and orthokeratotic hyperkeratosis.  The hyperkeratotic stratum corneum is infiltrated by few previously described fungal hyphae.  Diffusely, the superficial dermis is infiltrated by moderate numbers of lymphocytes, plasma cells, and fewer macrophages, and there is separation of dermal collagen by increased clear space (edema).  There is a focal intra-corneal pustule composed of degenerate neutrophils.  The follicle subjacent to this pustule is hyperkeratotic and contains a small amount of luminal amorphous eosinophilic cellular debris and few degenerate neutrophils (luminal folliculitis).

SLIDE B: Periodic Acid Schiff (PAS):  PAS-positive fungal hyphae are 2-4 um wide, septate, parallel walled, and exhibit dichotomous branching and are present on the allantoic membrane, parietal yolk sac, within chorioallantoic stroma and vessels, and within the stratum corneum of the skin. 

MORPHOLOGIC DIAGNOSIS: 

1. Placenta, chorioallantois and yolk sac: Placentitis and yolk sacculitis, necrotizing, subacute, diffuse, moderate, with necrotizing vasculitis, coccobacilli, and fungal hyphae, breed unspecified, bovine.

2. Haired skin: Dermatitis, lymphoplasmacytic and histiocytic, superficial interstitial, diffuse, subacute, moderate, with multifocal acanthosis, orthokeratotic hyperkeratosis, rare intracorneal pustules and neutrophilic luminal folliculitis, and few intracorneal fungal hyphae.

ETIOLOGIC DIAGNOSIS:  Mycotic placentitis, yolk sacculitis, and dermatitis

GENERAL DISCUSSION:

• Aspergillus fumigatus is the most common cause of mycotic placentitis in cattle
• Absidia, Mucor, Rhizopus, Mortierella, Candida and Torulopsis are other common causes

PATHOGENESIS:

• Bovine – usually hematogenous route to the placentomes by extension from forestomach or respiratory infections; portal of entry is unknown; in some cases, lesions begin in the placenta at the tip of the uterine horn and spread in a descending fashion
• Lesions begin in the cotyledons and spread to the intercotyledonary placenta

TYPICAL CLINICAL FINDINGS:

• Late term abortions - between the 6th and 8th month of gestation
• Placenta is often retained
• Majority of dams recover and can carry subsequent pregnancies to term

TYPICAL GROSS FINDINGS:

• Placenta
  • Placental lesions are both cotyledonary and intercotyledonary
  • Enlarged, yellow-brown, necrotic to hemorrhagic cotyledons with prominent margins (“cupping”) and thickened, opaque, yellow-brown, leathery intercotyledonary areas
• Fetus
  • Cutaneous lesions are multifocal, irregular, elevated, alopecic, gray plaques resembling ichthyosis or ringworm
  • Most common on the periorbital area, occiput, shoulders, back, and sides

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Placenta
  • Necrotizing placentitis with fungal hyphae, vasculitis and thrombosis
  • Endometrial lesions are less severe than those in the placenta
• Fetus
  • Cutaneous lesions: Hyperkeratosis, acanthosis, dermatitis
  • Infection is superficial, however invasion into hair follicles and dermis can occur

ADDITIONAL DIAGNOSTIC TESTS:

• Histochemical stains for fungi: Periodic acid Schiff (PAS), Gridley's, Grocott's methenamine silver nitrate (GMS)
• Culture of placenta and fetal skin or fetal gastric contents
• Immunohistochemistry
• ELISA of antibodies in serology

DIFFERENTIAL DIAGNOSIS:

Both cotyledonary and intercotyledonary bovine placentitis:

• Brucella abortus (R-B03): Cotyledonary necrosis, intercotyledonary areas thickened and leathery; numerous bacteria in chorionic epithelium and trophoblasts
• Coxiella burnetii (R-B07): Severe infections are rare in bovines, more often subclinical; trophoblasts with foamy cytoplasm (intracytoplasmic bacteria)

Late term abortion in cattle:

• Brucella abortus (R-B03), Campylobacter fetus venerealis (R-B10), Leptospira sp., Listeria monocytogenes, epizootic bovine abortion (foothills abortion; Pajaroellobacter abortibovis; R-B01), Salmonella sp., Sarcocystis cruzi

Fetal dermatitis with multifocal dermal plaques:

• Icthyosis fetalis (I-M08) or icthyosis congenita – an autosomal recessive molecular defect in many breeds of cattle that results in flat plates of hyperkeratosis; icthyosis fetalis is the more severe form compared to icthyosis congenita

Amniotic fluid changes: thick, white, yellow

• Ureaplasma diversum (R-B06)

COMPARATIVE PATHOLOGY:

Mycotic placentitis in other species:

• Mare: Aspergillus fumigatus and Mucor are the most common causes of equine mycotic abortion; infections are typically transcervical (i.e. ascending); grossly, there is brown inflammatory exudate that thickens the chorion adjacent to the cervical os (cervical star)
• Small ruminants: Campylobacter fetus fetus, Coxiella burnetti, Chlamydia sp., and Toxoplasma gondii are much more common causes of abortion than are fungi
• Swine: Viral and bacterial abortions are common; mycotic abortions are rare

REFERENCES:

1. Foster RA. Female reproductive system and mammae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:1181-1182.
2. Schlafer DH, Foster RA. Female genital system. In: Maxie MG, ed. Jubb, Kennedy, and Palmers Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Saunders Elsevier; 2016:398, 418-419.

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