JPC SYSTEMIC PATHOLOGY
REPRODUCTIVE SYSTEM
January 2022
R-M03

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, 5 x 10 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 um in diameter and have abundant vacuolated eosinophilic cytoplasm and multiple oval nuclei with clumped chromatin and one distinct nucleolus. Trophoblasts occasionally contain phagocytized erythrocytes.  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 um in diameter), with abundant, foamy, vacuolated cytoplasm (progestational stimulation) 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:

• Condition is unique to the bitch
• SIPS is a failure of trophoblasts that have penetrated the uterine wall to regress post-partum resulting in delayed re-epithelialization of the endometrium and prolonged uterine bleeding that manifests as bloody vaginal discharge lasting more than six weeks post-partum
• Trophoblasts within the endometrium and myometrium normally degenerate rapidly postpartum
• After whelping, uterine bleeding typically ceases within 7-10 days and uterine placental sites usually involute within 12 weeks
• SIPS does not affect the interplacental endometrium or ovaries
• More prevalent in young bitches
• May lead to ascending infection, endometritis, and open pyometra

PATHOGENESIS:

• Unknown

TYPICAL CLINICAL FINDINGS:

• Prolonged hemorrhagic vaginal discharge (>6 weeks)
• Abdominal pain and peritonitis may occur if the uterus ruptures at these sites
• Some bitches have no clinical signs and may recover spontaneously
• Anemia possible
• Can be fatal in bitches with coagulation disorders (e.g. vWD)

TYPICAL GROSS FINDINGS:

• Multiple segmental thickenings (ellipsoidal enlargements) of previous placental attachment sites visible from the serosal surface
• Endometrium is hemorrhagic and thickened
• Placental sites are raised, rough, gray-brown plaques
• Uterine lumen contains small amounts of serosanguinous fluid
• Endometrium between sites is normal
• 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, regenerating endometrium, and in deeper layers, syncytiotrophoblasts undergoing various stages of degeneration
  • Placental component of the lesion may contain masses of cells with closely packed, vesiculate nuclei and abundant foamy to vacuolated, pale, eosinophilic cytoplasm (syncytial trophoblasts 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
• Surface epithelium is usually detached, but when present has vacuolated cytoplasm, indicating progestational stimulation
• Endometrial glands are decreased in number and distended
• Necrotic areas may be mineralized
• Dense infiltration of lymphocytes, plasma cells, and macrophages may or may
• not surround the trophoblast cells

ADDITIONAL DIAGNOSTIC TESTS:

• Cytology, vaginal smear: Erythrocytes and syncytial trophoblasts
• Progesterone concentration (low)

DIFFERENTIAL DIAGNOSIS: 

For histologic findings:

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

COMPARATIVE PATHOLOGY:

• Hamster:
  • Giant trophoblastic cells appear in the myometrium during gestation and up to 3 weeks postpartum
  • Route of invasion is along the spiral uterine arteries
• Humans:
  • During pregnancy fetal trophoblasts invade the myometrium
  • Invasion similar to hamster and dog
  • Noninvolution of placental site is accompanied by failure of occlusion of placental vessels, resulting in hemorrhage
• Also described in a capybara

REFERENCES:

1. Al-Bassam MA, Thomson RG, O'Donnell L. Involution abnormalities in the postpartum uterus of the bitch. Vet Pathol 1981;18:208-218.
2. Foster, RA. Female reproductive system and mammae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6^th St. Louis, MO: Elsevier; 2017:1189.
3. 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.

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