Signalment (JPC #2373445): A thoroughbred mare

HISTORY: This mare aborted 8 weeks pre-term, with no prior history of reproductive problems.

HISTOPATHOLOGIC DESCRIPTION: Chorioallantois: Comprising 40% of this section of placenta, the allantoic stroma is focally markedly expanded up to 4x normal by numerous variably sized, up to 6 mm diameter, multifocal to coalescing, cystic, gland-like structures. The cysts are lined by epithelium that is attenuated, cuboidal, or ciliated columnar and piles up to 5 cell layers thick with a moderate to abundant amount of finely granular eosinophilic cytoplasm and are occasionally admixed with goblet cells. Cyst lumina contain an exudate composed of abundant viable and necrotic neutrophils admixed with amphophilic to eosinophilic secretory product, sloughed epithelial cells, mucin, deeply basophilic granular mineral, and necrotic debris. Diffusely, the allantoic epithelium is thickened up to 5 cell layers thick (hyperplasia), and there are scattered intraepithelial vacuoles that often contain similar exudate as within cysts. There is nearly diffuse squamous metaplasia of the chorionic epithelium, chorionic villi are absent, there is a small amount of fibrin and debris adhered to the chorionic epithelium, and there are few subepithelial lymphocytes. Diffusely within the chorioallantoic stroma, collagen fibers are separated by pale, finely granular eosinophilic material and lymphatics are filled with amorphous, eosinophilic, sparsely cellular, proteinaceous fluid (edema). Multifocally few neutrophils, lymphocytes, plasma cells, and macrophages infiltrate the stroma. Diffusely, there is mild congestion.

MORPHOLOGIC DIAGNOSES: Chorioallantois: Allantoic epithelial hyperplasia, adenomatous and cystic, focally extensive, moderate, with chorionic epithelial squamous metaplasia, Thoroughbred, equine.

CONDITION: Allantoic adenomatous hyperplasia; cystic adenomatous hyperplasia; dysplasia of the equine allantois

GENERAL DISCUSSION:

Rarely, adenomatous tumor-like structures (nodules or plaques) develop in the allantois of the placenta of the mare
Identified in several horse breeds; wide range of ages; may be under-reported
Chronic placentitis is the most common concurrent placental lesion, but placentitis and abortion are not always associated
The normal allantois is lined by physiologically active, non-glandular endoderm
Equine placentitis generally arises in the chorion; severe inflammation extends to the allantois

PATHOGENESIS:

Exact etiology and pathogenesis uncertain
Commonly associated with chronic placental lesions and primary bacterial or fungal placentitis
Two proposed mechanisms:
1. Intraepithelial gland formation inducing stromal proliferation, forming cystic masses
2. Invagination of exaggerated hyperplastic epithelium into allantoic stroma with formation of glands or cysts

Microorganisms isolated from affected placentas include Streptococcus sp., Leptospira sp., Escherichia coli, fungi, Pseudomonas aeruginosa, Klebsiella sp., Enterobacter sp, Nocardioform (e.g., N. actinomycetes), Amycolatropsis sp.

TYPICAL CLINICAL FINDINGS:

Late term abortion (7-11 months), stillbirths, premature births; usually with no previous history of reproductive problems

TYPICAL GROSS FINDINGS:

Two types of lesions:

Single or multiple, tan, firm and solid or cystic nodules up to 5 cm in diameter
Adenomatous plaques up to 2 cm thick and 20 cm in diameter

Clustered on the allantois, often near umbilical stalk

Cystic contents may be serous to mucoid with or without flocculent material
Associated chorionitis

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Allantois: Affected area is thickened by variably sized, hyperplastic glandular structures
1. Gland-like structures are separated by thickened, loosely arranged fibrovascular stroma lined by epithelium that is occasionally continuous with the allantoic surface
2. Larger glands are lined by epithelium with foamy cytoplasm, vesicular nuclei, and prominent cell borders
3. The gland lumina may contain proteinaceous and cellular debris
Chorionic epithelium: mild to moderate, chronic-active inflammation with chorionic villar necrosis or in some cases the chorion may lack villi
Three histologic classifications (Hong, Vet Pathol, 1993)
1. Stage one: Hypertrophy and hyperplasia of the allantoic epithelium with intracytoplasmic vacuoles and intraepithelial gland formation; cilia are discernible at the apical border of cells lining the lumen
2. Stage two: Presence of a group of glands in a thick, reactive allantoic stroma
3. Stage three: Nodular masses composed of numerous glands or cysts of various sizes in the allantoic stroma; glands or cysts lined by flat or low-medium columnar epithelium; lumina are empty or contain amphophilic amorphous material +/- neutrophils; desquamated epithelium

COMPARATIVE PATHOLOGY:

Elephants and rhinoceros: Similar allantoic nodules near umbilical stalks
Adenomatous hyperplasia is a common pathologic change occurring in many glandular tissues, including:
1. Mammary glands: Mammary fibroadenomatous hyperplasia; the most common mammary glandular change in cats, most commonly in young, intact queens, maybe in response to progesterone stimulation (more common in luteal phase)
2. Endometrium: Endometrial hyperplasia with adenomatous projections reported in zoo felids, spontaneously or more commonly in melengestrol acetate (MGA) for contraception, possibly related to estrogen-primed endometrium responding to progestins
3. Ovaries: Adenomatous hyperplasia of rete ovarii, a type of intraovarian cyst
4. Various endocrine glands (e.g., pituitary, thyroid, or adrenal glands)

REFERENCES:

Christensen BW, Roberts, JF, Posor MA, Giguere S, Sells SF, Donahue JM. Nocardioform placentitis with isolation of Amycolatropsis spp in a Florida-bred mare. J Am Vet Med Assoc. 2006;228(8):1234-1239.
Duncan M. Perissodactyls. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:433-34.
Foster RA, Premanandan C. Female Reproductive System and Mammae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1307.
Hong CB, et al. Adenomatous hyperplasia of equine allantoic epithelium. Vet Pathol 1993;30(2):171-175.
McEntee M, Brown T, McEntee K. Adenomatous dysplasia of the equine allantois. Vet Pathol 1988;25(5):387-389.
Shivaprasad HL, Sundberg JP, McEntee K, et. al. Cystic adenomatous hyperplasia of the equine allantois: a report of eight cases. J Vet Diagn Invest. 1994;6(1):107-110.
Solano-Gallego L, Masserdotti C. Chapter 13: Reproductive System. In: Raskin RE, Meyer DJ, & Boes KM eds. Canine and Feline Cytopathology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2022:452.
Terio KA, McAloose D, Mitchell E. Felidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:269.