Signalment (JPC #2033220): Two-year-old female shih tzu, post-partum

HISTORY: During a routine spay, the uterine wall was circumferentially and segmentally thickened near the bifurcation.

HISTOPATHOLOGIC DESCRIPTION: Uterus: Filling the uterine lumen and expanding the endometrium up to three times normal is a circumferential, irregular, 5x10 mm, multilobulated, eosinophilic coagulum that compresses the subjacent endometrium and myometrium, and focally extends into and replaces the outer muscular layer of the myometrium. There is a complex mosaic of coagulative necrosis throughout the coagulum which is admixed with hemorrhage, fibrin, mineral, and granular, extracellular bright yellow pigment (hematoidin). Multifocally, blood vessels contain poorly organized fibrin thrombin. Dispersed throughout the base of the coagulum are ectatic, tortuous endometrial glands. Within both the endometrium and subjacent myometrium are dilated, blood-filled sinuses separated by connective tissue and variable numbers of Iymphocytes, plasma cells, neutrophils, and hemosiderin-laden macrophages admixed with large, pleomorphic cells (syncytiotrophoblasts) that often surround endometrial and myometrial blood vessels. These syncytiotrophoblasts are 30-50 µm in diameter and have abundant vacuolated eosinophilic cytoplasm and multiple oval nuclei with clumped chromatin and one distinct nucleolus. Trophoblasts occasionally contain phagocytized erythrocytes or cellular debris. Multifocally, ectatic endometrial glands are lined by attenuated epithelium and contain necrotic debris, fibrin, erythrocytes, and scattered neutrophils. The adjacent endometrial epithelial cells are hypertrophic (up to 75 µm in diameter), with abundant, foamy, vacuolated cytoplasm (progestational change) and apically located nuclei. These cells often form focally extensive hyperplastic fronds or papillary projections and palisade along a fibrovascular stroma. Lymphatic vessels within the tunica muscularis are markedly ectatic (edema) and there is diffuse congestion of uterine blood vessels.

MORPHOLOGIC DIAGNOSIS: Uterus, placental site: Necrosis, coagulative, subacute, focally extensive, marked, with retention of syncytiotrophoblasts, endometrial hyperplasia, hemorrhage, and endometritis (subinvolution of placental sites), Shih Tzu, canine.

CAUSE: Unknown

CONDITION: Subinvolution of placental sites (SIPS)

GENERAL DISCUSSION:

SIPS is a condition unique to the bitch (more prevalent in younger) in which there is persistence of placental sites within the uterus after parturition beyond the normal 12 weeks
Due to a failure of trophoblasts regressing post-partum, resulting in prolonged uterine bleeding which manifests as bloody vaginal discharge lasting >6 weeks post-partum
1. SIPS does not affect the interplacental endometrium or ovaries
Normal gestation
1. Trophoblasts are found in the endometrium around blood vessels of the myometrium, but they rapidly degenerate after whelping
2. Uterine bleeding typically ceases within 7-10 days and uterine placental sites usually involute within 12 weeks
May lead to ascending infection, endometritis, and open pyometra

PATHOGENESIS:

Unknown

TYPICAL CLINICAL FINDINGS:

Prolonged hemorrhagic vaginal discharge (>6 weeks)
1. Anemia possible; can be fatal in bitches with coagulation disorders (e.g., von Willebrand’s disease)
2. Can result in uterine rupture
Some bitches have no clinical signs and may recover spontaneously

TYPICAL GROSS FINDINGS:

Multiple segmental thickenings (“ellipsoidal enlargements”) of previous placental attachment sites visible from the serosal surface
1. Placental sites are raised, rough, gray-brown plaques roughly twice as wide as normal (for that stage of regression)
2. Adjacent endometrium is hemorrhagic and thickened
3. Endometrium between sites is normal
4. Uterine lumen contains small amounts of serosanguinous fluid
Ovaries frequently have corpora lutea
The same uterus may display SIPS at some sites and normal involution at other sites

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Placental sites are composed of amorphous eosinophilic necrotic debris, fibrin, hemorrhage/hematoma and regenerating endometrium
1. In deeper layers, there is abundant eosinophilic matrix, hemorrhage, decreased density of endometrial glands and degenerating syncytiotrophoblasts
2. Placental component of the lesion may contain masses of cells with closely packed, abundant foamy to vacuolated, pale, eosinophilic cytoplasm and large, vesiculate nuclei (syncytiotrophoblasts or may represent decidual cells) that occur at the base of collagenous masses, often surround blood vessels, and may invade into the myometrium and/or through the serosa
Endometrial epithelium is usually detached, but when present has vacuolated cytoplasm, indicating progestational stimulation

ADDITIONAL DIAGNOSTIC TESTS:

Cytology, vaginal smear: Erythrocytes and syncytiotrophoblasts (especially if taken several weeks after whelping)
Progesterone concentration (low)

DIFFERENTIAL DIAGNOSIS:

For histologic findings:

Endometritis/metritis: Lacks persistent syncytiotrophoblasts
Pseudoplacentational endometrial hyperplasia: Associated with pseudopregnancy in the dog
1. Resembles pregnant uterus without fetal membranes and no trophoblasts
2. Villi extending from endometrial surface
3. Lumen filled with mucinous uterine secretions
Marked cystic endometrial hyperplasia
1. No trophoblasts
Normal placental involution
1. No deep invasion of trophoblasts
2. Involution should be complete by 12-15 weeks

COMPARATIVE PATHOLOGY:

This condition is described as unique to the bitch

REFERENCES:

Camus MS, Allison RW, Miller D. Female Reproductive Tract. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:423-438.
Foster RA, Premanandan C. Female Reproductive System and Mammae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1303-04.
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: Elsevier; 2016:440-442.