Pathology of the Placenta & Gestational Trophoblastic Disease Flashcards
How do hCG levels change in normal pregnancy, ectopic pregnancy, and trophoblastic disease states?
Normal pregnancy: Early rise to 10^5 or 10^6 range by fifth week, then fall to ~10^3 for remainder of pregnancy
Ectopic pregnancy: delayed rise to ~10^4 range before other evidence of ectopic pregnancy
Trophoblastic disease: slightly delayed rise compared to normal, but increase far above normal range and remain elevated.
What hCG levels correlate with US detectable gestational sac?
1,500 IU/ml = 5-6 weeks and tranvaginal US
4,000 IU/ml = 7 weeks and abdominal US
Where do the majority of ectopic pregnancies implant, and what are the diagnostic criteria?
90% implant in the fallopian tubes (other sites are ovary, abdominal cavity, and corneal tube)
35-50% associated with PID (also endometriosis, appendicitis)
Diagnostic: Clinical symptoms (sudden onset pain), B-hCG levels, ultrasound
What is the definition of trophoblastic diseases?
Group of rare tumors that involve abnormal growth of cells. Starting in the cells that would normally develop into the placenta.
- Can be either benign or malignant
- Some result from an abnormal conception/pregnancy
- Some are true neoplasms – uncontrolled tumor-forming proliferation of malignant trophoblast
What are the two types of molar pregnancies and what causes each?
Complete mole is diandric diploid (46, XX or XY) No maternal tissue
Partial mole is diandric triploid (69, XXY) 1/3 maternal tissue
Need both maternal and paternal DNA for normal development
Mom = embryonic tissue
Dad = placental tissue (hence over development of placental tissue/function in molar pregnancies)
What are the differences in US appearance and clinical consequences between partial and complete hydatidiform moles?
Partial: May have fetal parts
Large cystic spaces
Rarely recur or progress
Complete: Absence of fetal parts
“Snowstorm” appearance
Cystically dilated spaces without fetal parts
Potential to recur or become invasive
What are the signs and symptoms of a complete molar pregnancy?
Present with:
- elevated β-hCG,
- uterine size greater than dates,
- hyperemesis gravidarum,
- vaginal bleeding,
- early pre-eclampsia,
- hyperthyroidism
20% complete moles develop persistent Gestational Trophoblastic Disease
Recurrent or invasive Complete Hydatidiform Mole
Choriocarcinoma (1-2%)
How does a complete mole result in increased chances of gestational trophoblastic neoplasia?
Diandric cells have silenced p57kip2 genes.
p57kip2 is a cyclin dependent kinase inhibitor, loss of this gene may lead to neoplastic growth.
What are the gestational trophoblastic neoplasms?
Choriocarcinoma (gestational)
Placental site trophoblastic tumor
What are the signs of a choriocarcinoma?
Vaginal bleeding,
High serum β-hCG
Single/multiple hemorrhagic well-circumscribed nodules in uterus
Biphasic pattern w hemorrhage and necrosis
Marked nuclear atypia and mitoses
What are the four anatomic components of the placenta?
Chorionic plate
Parenchyma
Villi
Basal (maternal) plate
What is the chorionic plate?
tough fibrous layer that carries fetal blood vessels, often with atrophied villous remains (chorion frondosum)
What is found in the parenchyma?
Villous Tree
Maternal Blood
Fetal Vessels
What is found within the villi?
Stromal core with vessels
Cytotrophoblast - Inner, mononuclear
Syncytiotrophoblast - Outer, multinucleated
What does G5 P2123 mean?
P has four components (TPAL): Term delivery Preterm delivery Abortion (Less than 20 week delivery – spontaneous or induced) Living children
What are the three categories of placental injury, and what results from each?
Inflammatory
- Acute Chorioamnionitis
- Chronic Villitis or Deciduitis
Fetal Vascular Supply
- Maldevelopment – villous maturity, chorangioma
- Obstruction or Rupture – myonecrosis, hemorrhage
Maternal Vascular Supply
- Maldevelopment – abnormal implantation
- Obstruction or Rupture – infarction, abruption
What is chorioamnionitis?
Inflammation in the chorion
2° infection
Neutrophils (maternal) in fetal membranes
Poor correlation with clinical chorioamnionitis
Fever, leukocytosis, uterine tenderness, tachycardia
May be via ascending (cervico-vaginal flora) often GBS or trans-placental (hematogenous) routes often ToRCHeS (Toxoplasma, Rubella, CMV, HIV, HSV, Syphilis)
What are the ToRCHeS infections?
ToRCHeS (Toxoplasma, Rubella, CMV, HIV, HSV, Syphilis)
What is CMV Placentitis?
CMV = β-group herpesvirus, “owl’s eye” inclusion on histology
Common Infection
Primary or recurrent
Rarely problems (95% asymptomatic):
- IUFD (Intra-uterine fetal demise)
- IUGR (intra-uterine growth restriction)
- Deafness
Detection:
- Histology (placenta)
- Antibody testing
- Shell-virus urine culture
What are the common causes of infectious villitis and what are the clinical implications?
Syphilis- Perivascular fibrous proliferation
Toxoplasmosis - Granulomatous with cysts
Herpes- Multinucleated cells with inclusions
Listeria - Acute inflammation destroying villi
Clinical implications: Treatment for mother and child Unsuspected maternal immunosuppression Generally does not recur Public health/epidemiologic tracking Closure for family in poor outcomes
What are the two classes of villitis?
Infectious villitis
Villitis of unknown etiology
What is the histological findings in Villitis of Unknown Etiology and the clinical consequences?
Results in:
Agglutination/clumping of villi
Maternal lymphocytes attacking & destroying villi
Recurrence risk = 10-15% recur; ~2/3 IUFD or IUGR
Evaluation for infectious villitis
With stem villous/chorionic plate vasculitis = obliterative fetal vasculopathy
Independent risk factor for poor long-term fetal outcome
What conditions may lead to fetal vascular injury?
Meconium myonecrosis - meconium is toxic to vascular smooth muscle
Intervillous Thrombi - 1/5 of term placentas, leads to fetopmaternal hemorrhage (Kleinhauer-Betke test), laminated appearance (lines of Zahn)
Placental infarct - Acute cessation of maternal flow with live fetus Central more significant than peripheral Associated with IUGR, fetal hypoxia, IUFD
What are some conditions caused by abnormal placental location?
Placental accreta - Failure of decidual formation
Trophoblast invade abnormally deeply
Chorionic villi adhere to myometrium
Placenta Increta - Villi INVADE into myometrium
Placenta Percreta - Villi PENETRATE through serosa
Placenta Previa - Placenta covers the internal os
Increased risk for abruption, postpartum hemorrhage, C-section
Abruptio placentae - detachment of placenta from decidual seat, vaginal bleeding, abdominal/back pain, rapid uterine contractions
