Fetal/Placental Pathology

Question 1

Describe how a blastocyst implants into the endometrium around days 8-9 post-fertilization?

Answer 1

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.

Question 2

Answer 2

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

Question 3

Answer 3

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.

Question 4

What do placental ‘membranes’, that outline the uterine cavity where the fetus will develop, consist of?

Answer 4

These consist of decidua on the outside, hyalinized villi and trophoblasts in the middle, and the chorion (and amnion) on the inside.

Question 5

What does the placenta develop from?

Answer 5

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)

Question 6

What genes regulate placental development?

Answer 6

Homeobox genes ( HLX and DLX3 ) expressed in the trophoblast and its blood vessels

Question 7

How does maternal blood enter the intervillous space?

Answer 7

from the spiral endometrial arteries in the decidua basalis

Question 8

Question 9

Answer 9

Question 10

Question 11

Describe the development of the urachus?

Answer 11

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.

Answer 12

Question 13

What is symmetric growth restriction?

Answer 13

placental abnormalities/disruptions leading to all organ systems being similarly affected

Question 14

What are some causes of symmetric growth restriction?

Answer 14

Chromosomal disorders, congenital anomalies, and congenital infections.

Question 15

What types of infections fall can cause symmetric growth restriction?

Answer 15

•TORCH group of infections

toxoplasmosis,

other viruses and bacteria, such as syphilis.

rubella,

cytomegalovirus,

herpesvirus,

Question 16

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

Answer 16

T.

Question 17

What are some common sources of Uteroplacental insufficiency that can cause asymmetric growth restriction?

Answer 17

• 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.

Question 18

Third trimester loss is usually due to what?

Answer 18

placental insufficiency, whereas earlier losses are more likely due to chromosomal abnormalities

Question 19

Asymmetric etal growth restriction may also be due to maternal abnormalities or illnesses, not just placenta disruptions. Name some.

Answer 19

maternal conditions that result in decreased placental blood flow, including:

•Vascular diseases, such as preeclampsia (toxemia of pregnancy) and chronic hypertension

Question 20

What is a spontaneous abortion defined as?

Answer 20

(aka miscarriage)- this is loss of a pregnancy before 20 weeks of gestation, whereas loss of pregnancy after 20 weeks is called a stillbirth

Question 21

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?

Answer 21

maternal or fetal anatomical abnormalities and ascending infection

Question 22

What are some things included in ‘fetal or maternal structural abnormalities’ that commonly cause abortion in the second trimester?

Answer 22

• 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

Question 23

Infections are a common cause of fetal morbidity and mortality in the second trimester. What is one of the more common infections?

Answer 23

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

Question 24

How does Listeria affect a fetus? What about the mother?

Answer 24

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

Question 25

Question 26

What is this?

Answer 26

Deciduitis- acute exuate inflammation with microabscess (3-5 neutrophils collected together) formation within the decidua

Question 27

What are the main ways placental infections can occur?

Answer 27

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

Question 28

What constitutes a fetal inflammatory response?

Answer 28

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)

Question 29

•Inflammation in the umbilical vein is called what? the umbilical arteries?

Answer 29

phlebitis and arteritis

Question 30

Established or long standing infections of the umbilical cord can cause what?

Answer 30

tissue necrosis and accumulation of cellular debris (necrotizing funisitis)

Question 31

•Inflammation located at the periphery or surface of the umbilical cord may be the primary pattern seen. What is this called?

Answer 31

(peripheral funisitis)

Question 32

Describe umbilical infections caused by Candida albicans

Answer 32

Candida is a fungal organsm that is the most common cause of acute chorioamnionitis with peripheral funisitis. Most cases are diagnosed in preterm deliveries

Question 33

How would umbilica infections caused by Candida present grossly? histo?

Answer 33

● 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)

Question 34

What does this image show?

Answer 34

This is a chronic villitis with CMV

Question 35

How commonly does CMV cause chronic villitis?

Answer 35

It causes about 10% of chronic villitis cases, but often these infections present with no clinical symptoms

Question 36

When are fetal CMV infections most severe?

Answer 36

in placentas with plasmacytic villitis and inclusion bodies

Question 37

How would the placenta look during a chronic villitis due to CMV infection?

Answer 37

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

Question 38

T or F. Immunohistochemistry is often helpful in chronic villitis with CMV since histology often non-specific

Answer 38

T.

Question 39

How might a palcental Parvovirus B19 infection present?

Answer 39

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**

Question 40

Micro description: increased fetal erythroblasts with intranuclear inclusions and villous edema

Question 41

Question 42

What are monochorionic twins?

Answer 42

monozygotic (identical) twins that share the same placenta

Question 43

What is twin-twin transfusion syndrome?

Answer 43

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.

Question 44

During twin-twin transfusion syndrome, the twin that loses the blood when the blood supply is shunted to the other twin is called what?

Answer 44

donor twin (the other is the recipient twin) ## Footnote 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.

Question 45

What are the symptoms of TTTS?

Answer 45

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.

Question 46

The unequal size of identical twins is referred to as \_\_\_\_\_\_\_

Answer 46

discordant twins.

Question 47

Answer 47

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.

Question 48

Question 49

What is Placenta previa?

Answer 49

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

Question 50

What is Placenta accreta?

Answer 50

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.

Question 51

What is abruptio placenta?

Answer 51

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.

Question 52

Question 53

Question 54

What is Amnion Nodosum?

Answer 54

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

Question 55

Grossly describe amnion nodosum

Answer 55

Multiple yellow-tan superficial amniotic lesions, 0.2 to 0.4 cm and usually near insertion of umbilical cord

Question 56

Provide a micro description of amnion nodosum

Answer 56

* Nodules of protuberant eosinophilic fibrinous material with entrapped squamous cells * Associated with stratified squamous metaplasia

Question 57

What is Potter sequence?

Answer 57

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

Question 58

What are some causes of oligohydramnios?

Answer 58

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.

Question 59

What is preeclampsia?

Answer 59

The presentation of edema, HTN, and proteinuria typically beyond 20 weeks.

Question 60

How is the placenta involved in pereclampsia?

Answer 60

An ischemic placenta releases factors that affect the maternal endothelium

Question 61

How can the placenta appear in cases of preeclampsia?

Answer 61

Most placentas are smaller than expected (left: normal; right: preeclampsia) and Infarcts and retroplacental hematomas are more common

Question 62

How do placental infarcts from preeclampsia affect a neonate?

Answer 62

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.

Question 63

What are Syncytiotrophoblastic knots or syncytial knots?

Answer 63

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.

Question 64

There is fibrinoid necrosis of the vessel wall (strong eosinophilic staining areas). These are maternal vessels in the decidua.

Question 65

What is a molar pregnancy?

Answer 65

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

Question 66

What is a complete molar pregnancy?

Answer 66

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

Question 67

What risks are associated with complete molar pregnancies?

Answer 67

an increased risk of persistent trophoblastic disease (invasive mole) or 3% chance of turning into a choriocarcinoma

Question 68

T or F. In a complete molar pregnancy, there's no embryo or normal placental tissue

Answer 68

T.

Question 69

What is a partial molar pregnancy?

Answer 69

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.

Question 70

Question 71

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

Answer 71

T. A partial mole occurs due to fertilization of an egg with two sperm

Question 72

Are hCG levels elevated with a mole?

Answer 72

hCG very elevated in complete mole, slightly elevated in partial compared to normal levels for gestation

Question 73

What is the buzzword for a complete hydatidiform mole?

Answer 73

'Snowstorm"

Question 74

What is this?

Answer 74

A partial hydatidiform mole- some villi appear normal, whereas others are swollen, avascular, and grape-like (though not as large as a complete mole). ## Footnote There is minimal trophoblastic proliferation

Question 75

Question 76

What are gestational choriocarcinomas?

Answer 76

a malignant neoplasm of trophoblastic cells derived 50% from in moles, 25% in SAB, and 22% in normal pregnancies.

Question 77

How do gestational choriocarcinomas progress?

Answer 77

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.

Question 78

How do gestational choricocarcinomas appear histologically?

Answer 78

The tumor is composed of **syncytiotrophoblastic giant cells** in association with **cytotrophoblasts** on a highly **hemorrhagic background.**

Question 79

How do gestational choricocarcinomas appear grossly?

Answer 79

Choriocarcinoma is a soft, fleshy, yellow-white tumor that usually has large pale areas of necrosis and extensive hemorrhage

Question 80

What serum marker is usally high in gestational choriocarcinomas?

Answer 80

hCG

Question 81

Question 82

What are some main sequelae associated with premature delivery?

Answer 82

- Neonatal respiratory distress syndrome, also known as hyaline membrane disease - Necrotizing enterocolitis - Sepsis - Intraventricular and germinal matrix hemorrhage

Question 83

What is this?

Answer 83

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).

Question 84

Question 85

What is fetal hydrops?

Answer 85

accumulation of edema fluid in the fetus during intrauterine growth.

Question 86

What causes hydrops fetalis?

Answer 86

cardiovascular, chromosomal, fetal anemia (immune, Parvo B19, homozygous alpha-thalassemia), twin-twin, etc

Question 87

What are the main immune causes of hydrops fetalis?

Answer 87

Immune hydrops - The major antigens known to induce clinically significant immunologic reactions are certain of the Rh antigens and the ABO blood groups. ## Footnote The reaction occurs in **second and subsequent pregnancies** in an Rh-negative mother with an Rh-positive father.

Question 88

Why does hydrops fetalis develop via RH factor differences (ie RH negative mom and RH positive fetus)?

Answer 88

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

Question 89

What is this? When does it classically occur?

Answer 89

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)**

Question 90

What is SIDS?

Answer 90

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)

Question 91

What causes SIDS?

Answer 91

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.