JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1454646): A 13-year-old female dog
HISTORY: This dog presented with a distended abdomen.
HISTOPATHOLOGIC DESCRIPTION: Uterus: The uterine wall is circumferentially thinned secondary to marked luminal dilation. Diffusely filling the lumen, infiltrating the ulcerated endometrium and underlying uterine stroma and separating, surrounding and filling endometrial glands are many viable and degenerate neutrophils, fewer epithelioid macrophages, lymphocytes, plasma cells, hemorrhage, fibrin and eosinophilic cellular and karyrorrhectic debris (necrosis). Endometrial glands are often ectatic and lined by attenuated to cuboidal epithelium or, occasionally, by tall columnar, pseudostratified epithelium which contains abundant eosinophilic foamy cytoplasm and vesiculate nuclei (progestational epithelium). Multifocally, glandular epithelium is disrupted and replaced by eosinophilic cellular and karyorrhectic debris (necrosis) and fibrin. Endometrial lymphatics are ectatic (edema) and blood vessels are congested. The deep endometrial stroma is edematous and contains moderate numbers of large foamy macrophages.
MORPHOLOGIC DIAGNOSIS: Uterus: Endometritis, necrosuppurative, diffuse, moderate, with ectatic glands, breed unspecified, canine.
ETIOLOGY: Bacterial infection of progesterone-primed endometrium
ETIOLOGIC DIAGNOSIS: Bacterial endometritis
- Endometritis: involvement of primarily uterine mucosa (endometrium – mucosa, glands and endometrial stroma)
- Start as inflammation of endometrium that progress to myometrium, becoming metritis (Inflammation of all layers of the uterine wall)
- Chronic endometritis: characterized by productive fibrosis lymphocytes and plasma cells
- The most common isolate is Escherichia coli (fecal isolates and urinary tract pathogens); pyometra may also be caused by other normal vaginal microorganisms or urinary tract pathogens (Staphylococcus , Streptococcus sp., Klebsiella sp., Pseudomonas sp., Proteus sp., Hemophilus sp., Pasteurella sp., Serratia sp.)
- Pyometra: acute or chronic suppurative infections with pus accumulation in the uterine lumen
- Common in bitches and cows, less so in other species
- In bitches and queens, most frequent weeks after estrus (during diestrus), with associated endometrial hyperplasia due to progesterone influence; associated with endometrial hyperplasia in bitches
- Extragenital lesions are also present due to toxemia and intermittent bacteremia
- In younger dogs is associated with estrogen administration for prevention of pregnancy (mismating injection)
- Uterine susceptibility to infection is highest during the luteal phase of the estrous cycle
- Progesterone is the dominate hormone during diestrus and causes increased susceptibility to infection via:
- Increased endometrial growth and glandular secretion
- Continued closure of cervix
- Decreased migration of neutrophils to the uterus and reduced phagocytosis of uterine bacteria
- Secretion of progesterone-induced immunosuppressants
- Pyometra typically develops a few weeks after estrus in the bitch
- The endometrial response to progesterone depends on estrogen priming in dogs and cats
- Recent evidence suggests that any appropriate stimulus to a progesterone-primed uterus can produce cystic endometrial hyperplasia (CEH); bacterial infection of the progesterone-primed uterus can cause both CEH and pyometra
- Cystic Endometrial Hyperplasia (CEH)
- Results in accumulation of endometrial excretions
- May involve a single gland, few glands, or entire surface
- May be due to prolonged estrogenic stimulation in some species
- Membranoproliferative glomerulonephritis results from immune complex deposition may be a sequelae
- Endometritis may also occur post-coitus in all species, but is typically mild
TYPICAL CLINICAL FINDINGS:
- Depression, anorexia, vomiting, polyuria/polydipsia, gait abnormalities and lameness
- Most pyometras are closed-cervix but if the cervix is open, there is a serosanguinous to mucopurulent discharge from the vagina
- Neutrophilia often with a left shift (may be degenerative with toxic changes), in pyometra
- In chronic cases, there is normocytic, normochromic, nonregenerative anemia
- Hyperproteinemia and hyperglobulinemia
- Hypoglycemia is possible with sepsis
- Isosthenuria or hyposthenuria
- Endotoxin (usually coli) impairs sensitivity of collecting tubular epithelial cells to ADH > polyuria/polydypsia
TYPICAL GROSS FINDINGS:
- Uterine enlargement
- Serosa is dark with congested vessels
- Uterine wall is friable; rupture may occur, with subsequent peritonitis
- Character of the pus varies with causative agent:
- E. coli and Proteus sp. produce thick, viscid, tenacious, opaque to brown material that has a characteristic fetid odor
- Staphylococcus and Streptococcus sp. produce a typically yellow purulent exudate
- Irregularly thickened mucosa with patchy areas of necrosis and ulceration
- Hyperplastic endometrium which contains small cysts and is dull white
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Progestational changes to the endometrial epithelium in bitches:
- Enlarged, tall columnar, and vacuolated with pyknosis
- Pseudostratification or papillary proliferations
- In acute stage, numerous neutrophils in the lumen and infiltrating the epithelium and stroma
- Characterized by plasma cells, with foci of lymphocytes in the stroma in all species
- Chronic infection may be accompanied by fibrosis, hyperplasia and squamous metaplasia of surface epithelium
- Variably cystic glands
- Non-uterine lesions (in bitch): Bone marrow depression, widespread extramedullary hematopoiesis, and immune complex glomerulonephropathy
ADDITIONAL DIAGNOSTIC TESTS:
For an enlarged uterus:
- Hydrometra or mucometra; sterile fluid or mucus in the uterus that develops in association with endometrial hyperplasia
- Cow: Uterine disease associated with pyometra inhibits the synthesis and release of prostaglandin F2-alpha, the luteolytic factor, leading to persistence of the corpus luteum (CL) and high progesterone levels; pyometra usually occurs early postpartum or following a breeding-induced venereal infection
- Common agents include Streptococci, Staphylococci, coliforms, pyogenes, Pseudomonas and T. foetus after breeding
- Cattle with tuberculosis may have uterine lesions including miliary and diffuse caseating forms
- Coxiella burnetti may also cause severe chronic endometritis
- Endometritis may be associated with bovine herpesvirus 4
- Queen: Pyometra develops 2-5 weeks after estrus; approximately 50% of affected cats do not have a CL which is associated with pyometra development, and the association with endometrial hyperplasia is not clear; the cat is an induced ovulatory
- Mare: Most mares continue to cycle during disease but estrous cycle length may be affected will decrease fertility; pyometra in the mare rarely leads to systemic disease and cystic enodmetrial hyperplasia is very uncommon in mares
- Most common after foaling and breeding
- Taylorella equigenitalis (contagious equine metritis organism): venereal disease of mares that cause temporary infertility
- Doe: Pasteurella multocida and Staphylococcus aureus frequently isolated in pyometra or metritis
- Non-human primates: coli and coagulase-positive Staphylococcus sp. are the most common isolates
- Ewe: Uncommon; recent association with indwelling central venous catheter and Staphylococcus aureus
- Sow: Uncommon
- Zoo canids: Red wolves, maned wolves, African wild dogs, bat eared foxes and others treated with melengestrol acetate, a contraceptive, are prone to development of uterine lesions including cystic endometrial hyperplasia, uterine mineralization, pyometra and endometritis
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- Moresco A, Munson L, Gardner IA. Naturally occurring and melengestrol acetate-associated reproductive tract lesions in zoo canids. Vet Pathol. 2009;46(6):1117-1128.
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- Zhao JL, Ding YX, Zhao HX, et al. Presence of superantigen genes and antimicrobial resistance in Staphylococcus isolates obtained from the uteri of dairy cows with clinical endometritis. Vet Rec. 2014;175(14):352.