JPC SYSTEMIC PATHOLOGY
REPRODUCTIVE SYSTEM
January 2022
R-M02 (NP)
Signalment (JPC #2118235): Female chinchilla
HISTORY: None.
HISTOPATHOLOGIC DESCRIPTION: Lung: Multifocally, alveolar capillary lumens are occluded by small aggregates of irregularly round, uninucleate or binucleate, placental trophoblasts which measure up to 150 um in diameter. Trophoblasts have an abundant amount of amphophilic, finely granular to microvacuolated cytoplasm and round to oval, 30-50 um diameter nuclei with clumped chromatin. Diffusely, alveolar septa are mildly expanded by dilated capillaries, edema, fibrin, low numbers of lymphocytes, and fewer neutrophils. Multifocally, alveolar lumina contain an increased number of alveolar macrophages and a minimal amount of fibrin.
Uterus: Essentially normal tissue.
MORPHOLOGIC DIAGNOSIS: Lung, alveolar capillaries: Trophoblast emboli, multifocal, mild, chinchilla (Chinchilla lanigera), rodent.
GENERAL DISCUSSION:
- Trophoblasts line the chorion; functions include:
- Invasion of the maternal endometrium and establishment/initiation of placentation
- Modulation of maternal vascular dilation
- Inhibition of uterine prostaglandin secretion to preserve the corpora lutea
- Protection of the fetus from maternal immune responses
- Four types of trophoblasts
- Cytotrophoblast – mononuclear trophoblast precursor; mitotically active
- Villous syncytiotrophoblast – endocrinologically active; secretes hCG in humans; non-mitotic multinucleated cells
- Junctional trophoblast – attaches anchoring villi to maternal deciduas
- Invasive intermediate trophoblast – migrates into deciduas, myometrium, and arteries of uterus
PATHOGENESIS:
- Animals with hemochorial placentation have fetal trophoblastic cells in direct contact with the maternal circulation
- There is loss of endothelium, elastic membrane, and smooth muscle in affected arteries with no reaction from the maternal immune system
- In animals with hemochorial placentation, trophoblast deportation is a feature of normal pregnancy as part of the normal lifecycle of the syncytiotrophoblast as they undergo apoptosis (physiologic desquamation)
- Shedding of syncytial knots (i.e. large, multinucleate trophoblast cells) à enter maternal circulation à transported to lungs à lodge in capillaries à phagocytosed by pulmonary endothelium
- If the syncytiotrophoblasts are necrotic due to placental hemodynamic abnormalities (i.e. as in eclampsia) that may result in trophoblast necrosis in lieu of apoptosis à same process as above, except once phagocytosed by pulmonary endothelium, those endothelial cells become activated à release IL-5, IL-6, and TNF-alpha à systemic endothelial activation à pre-eclampsia/eclampsia
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Large, multinucleate trophoblast cells (syncytial knots) within maternal small pulmonary vessels without an inflammatory reaction
ADDITIONAL DIAGNOSTIC TESTS:
- Immunohistochemistry: Cytokeratin positive
DIFFERENTIAL DIAGNOSIS:
- Neoplastic emboli (choriocarcinoma, placental site trophoblastic tumor)
- Megakaryoctyes
COMPARATIVE PATHOLOGY:
- Syrian hamsters are a model for trophoblast-blood vessel interaction
REFERENCES:
- Burek JD, Goldberg B, Hutchins G, Strandberg JD. The pregnant Syrian hamster as a model to study intravascular trophoblasts and associated maternal blood vessel changes. Vet Pathol. 1979;16(5):556‑566.
- Chen Q, Stone P, Ching LM, Chamley L. A role for interleukin-6 in spreading endothelial cell activation after phagocytosis of necrotic trophoblastic material: implications for the pathogenesis of pre-eclampsia. J Pathol. 2009;217(1):122-130.
- Kliman HJ. Uteroplacental blood flow. The story of decidualization, menstruation and trophoblast invasion. Am J Pathol. 2000;157(6):1759-1768.
- La Perle KMD, Green MG, Niewiesk S. Trophoblast Deportation to the Lungs of Cotton Rats (Sigmoden hispidus). Comp Med. 2014;64(6):448-455.
- Noden DM, De Lahanta A. The Embryology of Domestic Animals: Developmental Mechanisms and Malformations. Baltimore, MD: Williams and Wilkins;1985:50‑69.
- Tvedten HW, Langham RF. Trophoblastic emboli in a chinchilla. J Am Vet Med Assoc. 1974;165(9):828‑829.
