Fetal/Placental Pathology Flashcards
Describe how a blastocyst implants into the endometrium around days 8-9 post-fertilization?
It is likely that some adhesion molecules are essential for blastocyst attachment to the endometrium. Once the trophoblastic shell has attached, marked changes occur on its surface and invasion is accomplished by dissociation and ingestion of endometrial cells.
So at approx 14 days from fertilization, the chorion extends its CT into the developing villi, the umbilical cord begins to develop from embryonic mesoderm, and the amnion fills with fluid, and then the embryo herniates into the amniotic cavity
With continued expansion of the embryonic cavity, the surface of the ovum becomes attenuated, the peripheral villi atrophy (with partial decidua necrosis), and the future placental “membranes” form.
What do placental ‘membranes’, that outline the uterine cavity where the fetus will develop, consist of?
These consist of decidua on the outside, hyalinized villi and trophoblasts in the middle, and the chorion (and amnion) on the inside.
What does the placenta develop from?
The placenta is a fetomaternal organ that has two components:
A fetal part that develops from the chorionic sac, the outermost fetal membrane
A maternal part that is derived from the endometrium
There is a placental membrane that acts as a location between the fetus and mother where blood and nutrients can be exchanges (villi)
What genes regulate placental development?
Homeobox genes ( HLX and DLX3 ) expressed in the trophoblast and its blood vessels
How does maternal blood enter the intervillous space?
from the spiral endometrial arteries in the decidua basalis
Describe the development of the urachus?
During the third week of development, the allantois protrudes into the area of the urogenital sinus.
Between the 5th and 7th week of development, the allantois will become the urachus, a duct between the bladder and the yolk sac. A patent allantois can result in urachal cyst.
What is symmetric growth restriction?
placental abnormalities/disruptions leading to all organ systems being similarly affected
What are some causes of symmetric growth restriction?
Chromosomal disorders, congenital anomalies, and congenital infections.
What types of infections fall can cause symmetric growth restriction?
•TORCH group of infections
toxoplasmosis,
other viruses and bacteria, such as syphilis.
rubella,
cytomegalovirus,
herpesvirus,
T or F. asymmetric growth restriction spares the brain and is caused by a down-regulation of growth in the latter half of gestation due to placental disruptions
T.
What are some common sources of Uteroplacental insufficiency that can cause asymmetric growth restriction?
- umbilical-placental vascular anomalies (such as single umbilical artery, abnormal cord insertion, placental hemangioma),
- placental abruption,
- placenta previa,
- placental thrombosis and infarction,
- placental infection , or
- multiple gestations.
Third trimester loss is usually due to what?
placental insufficiency, whereas earlier losses are more likely due to chromosomal abnormalities
Asymmetric etal growth restriction may also be due to maternal abnormalities or illnesses, not just placenta disruptions. Name some.
maternal conditions that result in decreased placental blood flow, including:
•Vascular diseases, such as preeclampsia (toxemia of pregnancy) and chronic hypertension
What is a spontaneous abortion defined as?
(aka miscarriage)- this is loss of a pregnancy before 20 weeks of gestation, whereas loss of pregnancy after 20 weeks is called a stillbirth
Again, most early SABs are due to chromosomal abnormalities, while the majorty of third trimester stillbirths are due to placental insufficiency. What causes the majority of pregnancy loss in the second trimester?
maternal or fetal anatomical abnormalities and ascending infection
What are some things included in ‘fetal or maternal structural abnormalities’ that commonly cause abortion in the second trimester?
- Maternal endocrine factors , including luteal-phase defect, poorly controlled diabetes, and other uncorrected endocrine disorders.
- Physical defects of the uterus , such as submucosal leiomyomas, uterine polyps, or uterine malformations, may prevent or disrupt implantation
- Systemic disorders affecting the maternal vasculature , such as antiphospholipid antibody syndrome, coagulopathies, and hypertension
Infections are a common cause of fetal morbidity and mortality in the second trimester. What is one of the more common infections?
Infections can either be ascending (more common) or blood-bourne. A particularly common blood-bourne fetal infection arises from Listeriosis infection, in which Listeria spp. from food (delis, unpasteurized drinks, sushi) enters from the GI and passes through the placenta
How does Listeria affect a fetus? What about the mother?
Listeriosis is a rare disease that causes mild maternal illness, but can be devastating to the fetus. Listeria’s obligate intracellular nature make it a difficult infection to diagnose and treat
It can also cause severe disease in the neonate, including death
What is this?
Deciduitis- acute exuate inflammation with microabscess (3-5 neutrophils collected together) formation within the decidua
What are the main ways placental infections can occur?
they can occur hematogenously or trans-placental. These are typically the TORCH infections and cause a chronic-villitis vs.
ascending from the birthing canal and these cause acute chorioamnionitis
What constitutes a fetal inflammatory response?
Inflammation of umbilical vessels (vasculitis) and cord substance (Wharton’s Jelly) (funisitis) occurs in response to infection, and constitutes the fetal inflammatory response (while choricoamnioitis is the maternal response)
•Inflammation in the umbilical vein is called what? the umbilical arteries?
phlebitis and arteritis
Established or long standing infections of the umbilical cord can cause what?
tissue necrosis and accumulation of cellular debris (necrotizing funisitis)
•Inflammation located at the periphery or surface of the umbilical cord may be the primary pattern seen. What is this called?
(peripheral funisitis)
Describe umbilical infections caused by Candida albicans
Candida is a fungal organsm that is the most common cause of acute chorioamnionitis with peripheral funisitis. Most cases are diagnosed in preterm deliveries
How would umbilica infections caused by Candida present grossly? histo?
● Gross description: well-circumscribed, pale yellow plaques scattered over the surface of the umbilical cord (top)
● Micro description: microabscesses containing yeast in subamniotic layer of umbilical cord; chorioamnionitis or necrotizing funisitis may be present (bottom)
What does this image show?
This is a chronic villitis with CMV
How commonly does CMV cause chronic villitis?
It causes about 10% of chronic villitis cases, but often these infections present with no clinical symptoms
When are fetal CMV infections most severe?
in placentas with plasmacytic villitis and inclusion bodies
How would the placenta look during a chronic villitis due to CMV infection?
placenta may be large and edematous or small and fibrotic
Micro description: lymphocytic or plasmacytic villitis with hyalinized villi and mineralization; Hofbauer cell (fetal macrophage) hyperplasia, rare intranuclear and cytoplasmic inclusions
T or F. Immunohistochemistry is often helpful in chronic villitis with CMV since histology often non-specific
T.
How might a palcental Parvovirus B19 infection present?
B19 destroys early RBCs (normoblasts), causing anemia and resultant fetal hydrops with marked erythroid hypoplasia of bone marrow and occasional giant erythroblasts. Fetuses may also develop myocarditis
Micro description: increased fetal erythroblasts with intranuclear inclusions and villous edema
What are monochorionic twins?
monozygotic (identical) twins that share the same placenta
What is twin-twin transfusion syndrome?
A complication of monochorionic twin pregnancy. Monochorionic twin placentas have vascular anastomoses that connect the circulations of the twins, and in some cases these connections include one or more arteriovenous shunts. If these shunts preferentially increase blood flow to one twin at the expense of the second, one twin will be underperfused, while the second will be fluid overloaded.
It is this phenomenon that constitutes the twin-twin transfusion syndrome, which if severe may result in the death of one or both fetuses.
During twin-twin transfusion syndrome, the twin that loses the blood when the blood supply is shunted to the other twin is called what?
donor twin (the other is the recipient twin)
Both infants may have problems depending on how much blood is passed from one to the other. The donor twin may have too little blood, and the other may have too much blood.
What are the symptoms of TTTS?
Most of the time, the donor twin is smaller than the other twin at birth. The donor infant often has anemia, is dehydrated, and looks pale.
The recipient twin is born larger, with redness to the skin, too much blood, and a higher blood pressure. The twin that gets too much blood may develop cardiac failure because of the high blood volume.
The unequal size of identical twins is referred to as _______
discordant twins.
Most of the time, the donor twin is smaller than the other twin at birth. The infant often has anemia, is dehydrated, and looks pale.
The recipient twin is born larger, with redness to the skin, too much blood, and a higher blood pressure. The twin that gets too much blood may develop cardiac failure because of the high blood volume.
What is Placenta previa?
This results from a very low lying placenta or a placenta which cover the os. Obviously, severe hemorrhage can result with cervical dilation and passage of the baby through the birth canal
What is Placenta accreta?
results from a lack of formation of a normal decidual plate. Thus, the chorionic villi extend into myometrium, and the placenta cannot separate normally following delivery. Severe hemorrhage results.
What is abruptio placenta?
This results from premature separation of the placenta prior to delivery, with formation of a retroplacental blood clot. The blood supply of oxygen and nutrients to the fetus is compromised to a greater degree with increasing size of the abruption.
What is Amnion Nodosum?
This is seen in placentas affected by oligohydramnios, which may be associated with fetal renal agenesis and pulmonary hypoplasia
May be due to desquamated skin or membrane injury
Grossly describe amnion nodosum
Multiple yellow-tan superficial amniotic lesions, 0.2 to 0.4 cm and usually near insertion of umbilical cord
Provide a micro description of amnion nodosum
- Nodules of protuberant eosinophilic fibrinous material with entrapped squamous cells
- Associated with stratified squamous metaplasia
What is Potter sequence?
the atypical physical appearance of a fetus or neonate due to oligohydramnios experienced in the uterus. Oligohydramnios is the decrease in amniotic fluid volume sufficient to cause deformations in morphogenesis of the fetus
clubbed feet, pulmonary hypoplasia, and cranial anomalies = potters sequence
What are some causes of oligohydramnios?
It can be caused by renal diseases such as bilateral renal agenesis (BRA), atresia of the ureter or urethra causing obstruction of the urinary tract, polycystic or multicystic kidney diseases, renal hypoplasia, amniotic rupture, toxemia, oruteroplacental insufficiency from maternal hypertension.
What is preeclampsia?
The presentation of edema, HTN, and proteinuria typically beyond 20 weeks.
How is the placenta involved in pereclampsia?
An ischemic placenta releases factors that affect the maternal endothelium
How can the placenta appear in cases of preeclampsia?
Most placentas are smaller than expected (left: normal; right: preeclampsia) and Infarcts and retroplacental hematomas are more common
How do placental infarcts from preeclampsia affect a neonate?
small infarcts may be of no consequence to the fetus, but if more than a third or half of the placental parenchyma is infarcted or lost in some fashion, then the blood supply to the fetus can become severely compromised and fetal demise may occur.
What are Syncytiotrophoblastic knots or syncytial knots?
These are aggregates of syncytial nuclei at the surface of terminal villi, commonly seen in preeclampsia.
In the term placenta, most syncytial knots are thought to be artifacts from tangential sectioning while the minority are syncytial sprouts, bridges, or apoptotic knots. Syncytial knots are consistently present, increasing with increasing gestational age, and can be used to evaluate villous maturity. Increased syncytial knots are associated with conditions of uteroplacental malperfusion and are important in placental examination.
There is fibrinoid necrosis of the vessel wall (strong eosinophilic staining areas). These are maternal vessels in the decidua.
What is a molar pregnancy?
also known as hydatidiform mole —this is a noncancerous (benign) tumor that develops in the uterus. A molar pregnancy starts when an egg is fertilized, but instead of a normal, viable pregnancy resulting, the placenta develops into an abnormal mass of cysts, often described as a grapelike cluster
What is a complete molar pregnancy?
A complete mole is caused by a single (incidence is about 90%) or two (incidence is about 10%) sperm combining with an egg which has lost its DNA (the sperm then reduplicates forming a “complete” 46 chromosomeset), The genotype is typically 46,XX (diploid) due to subsequent mitosis of the fertilizing sperm, but can also be 46,XY (diploid). 46,YY (diploid) is not observed
What risks are associated with complete molar pregnancies?
an increased risk of persistent trophoblastic disease (invasive mole) or 3% chance of turning into a choriocarcinoma
T or F. In a complete molar pregnancy, there’s no embryo or normal placental tissue
T.
What is a partial molar pregnancy?
A partial mole occurs when a haploid egg is fertilized by two sperm or by one sperm which reduplicates itself yielding the genotypes of 69,XXY (triploid) or 92,XXXY (tetraploid).
In a partial molar pregnancy, there’s an abnormal embryo and possibly some normal placental tissue. The embryo begins to develop but is malformed and can’t survive.
T or F. A Complete mole occurs when an egg that has lost its female chromosomes, and as a result the genetic material is completely paternally derived
T. A partial mole occurs due to fertilization of an egg with two sperm
Are hCG levels elevated with a mole?
hCG very elevated in complete mole, slightly elevated in partial compared to normal levels for gestation
What is the buzzword for a complete hydatidiform mole?
‘Snowstorm”
What is this?
A partial hydatidiform mole- some villi appear normal, whereas others are swollen, avascular, and grape-like (though not as large as a complete mole).
There is minimal trophoblastic proliferation
What are gestational choriocarcinomas?
a malignant neoplasm of trophoblastic cells derived 50% from in moles, 25% in SAB, and 22% in normal pregnancies.
How do gestational choriocarcinomas progress?
Choriocarcinoma is rapidly invasive and metastasizes widely to the lungs, but once identified responds well to chemotherapy.
Mitoses are abundant and sometimes abnormal. The tumor invades the underlying myometrium, frequently penetrates blood vessels, and in some cases extends out onto the uterine serosa and into adjacent structures.
How do gestational choricocarcinomas appear histologically?
The tumor is composed of syncytiotrophoblastic giant cells in association with cytotrophoblasts on a highly hemorrhagic background.
How do gestational choricocarcinomas appear grossly?
Choriocarcinoma is a soft, fleshy, yellow-white tumor that usually has large pale areas of necrosis and extensive hemorrhage
What serum marker is usally high in gestational choriocarcinomas?
hCG
What are some main sequelae associated with premature delivery?
- Neonatal respiratory distress syndrome, also known as hyaline membrane disease
- Necrotizing enterocolitis
- Sepsis
- Intraventricular and germinal matrix hemorrhage
What is this?
Necrotizing enterocolitis (NEC).
A, entire small bowel is markedly distended with a perilously thin wall (impending perforation).
B, The congested portion of the ileum corresponds to areas of hemorrhagic infarction and transmural necrosis microscopically. Submucosal gas bubbles (pneumatosis intestinalis) can be seen in several areas (arrows).
What is fetal hydrops?
accumulation of edema fluid in the fetus during intrauterine growth.
What causes hydrops fetalis?
cardiovascular, chromosomal, fetal anemia (immune, Parvo B19, homozygous alpha-thalassemia), twin-twin, etc
What are the main immune causes of hydrops fetalis?
Immune hydrops - The major antigens known to induce clinically significant immunologic reactions are certain of the Rh antigens and the ABO blood groups.
The reaction occurs in second and subsequent pregnancies in an Rh-negative mother with an Rh-positive father.
Why does hydrops fetalis develop via RH factor differences (ie RH negative mom and RH positive fetus)?
Rh+ eryhtrocytes get into maternal circulation where they are recognized as foreign bodies and an immune response is made against them where IgG ABs are made that can cross the placenta and enter the fetal circulation causing:
lysis of RBCs, leading to anemia, and then extramedullary hematopoiesis and cardiac decompensation (causes the edema), as well as
bilirubin release from degraded hemoglobin which produced jaundice and kernicterus
What is this? When does it classically occur?
Fluid accumulation is particularly prominent in the soft tissues of the neck, and this condition has been termed cystic hygroma.
Cystic hygromas are characteristically seen, but not limited to, constitutional chromosomal anomalies such as 45,X karyotypes (aka Turner syndrome)
What is SIDS?
defined as “the sudden death of an infant under 1 year of age which remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history.”
sudden unexpected infant death (SUID)
What causes SIDS?
A “triple-risk” model of SIDS has been proposed, which postulates the intersection of three overlapping factors:
(1) a vulnerable infant,
(2) a critical developmental period in homeostatic control, and
(3) an exogenous stressor.
