Wednesday, February 28, 2001 Guerrero and Morales Mafia

Pathology 10am Viviane Mamlok, M.D.

Placental Pathology

Introduction Comments: Placentas are a messy portion of pathology, everybody hates them but she loves them.

I. Placenta

Slide #1a [Robbins fig 24-55a], placenta resembles an “upside-down tree” that attaches to the uterine wall; It gives all the good stuff to the baby from the mom and takes all the waste products from the baby to the mom who then serves as a garbage disposal unit. Looking at the placenta, you have a fetal surface with the famous extension cord to the baby and the maternal surface is the thing that is attached to the uterine wall. The maternal surface is rugged whereas the fetal surface is smooth and shiny. Here you have the maternal surface, there is the famous umbilical cord. The maternal blood goes through the umbilical vein to the baby and the waste products are returned to the mother through the two umbilical arteries.

Slide #1b [Robbins fig 24-55b] This is the maternal surface that looks like a big juicy hamburger patty from McDonalds.

Slide #2 micro of normal placenta (immature): What is the placenta made out of? It's made out of chorionic villi. Basically a placenta looks like an upside down flowerpot?? (Scribe note: I have no idea what she is talking about) Chorionic villi are made out of stroma and around it you have the outer surface which is syncytiotrophoblast. Below it you have a layer of cytotrophoblast. Lastly, deeply buried in the stroma of immature villi you see few capillaries.

Slide #3 micro of mature placenta: placenta is aging and running on its last legs. Chorionic villi are mature and much smaller. There is much less intervening stroma and capillaries are much more prominent. Intervillous spaces contain maternal blood, capillaries of chorionic villi contain fetal blood. In-between them are as little as one endothelial cells so exchange is very east at this point.

II. Spontaneous Abortion

A. Occurs in 10-15% of pregnancies

B. Fetal causes

1. Chromosomal abnormalities

a. Majority of cases, >50% of spontaneous abortions

b. Turner syndrome, triploidies

c. Do chromosome studies in the case of recurrent abortion or if you see something obviously wrong with the baby

2. Defect in implantation into uterine wall

C. Maternal causes

1. Infection

2. Uterine abnormalities

3. Trauma

4. Substance abuse

III. Ectopic Pregnancy

A. Fetal implantation occurs outside the uterus

1. Fallopian tubes (90%)

2. Within an ovary

3. Freely within the abdomen

4. Cornua (intra-uterine portion of fallopian tube)

B. Seen in 1/150 pregnancies

C. Patient presents with intense pain 6 weeks after last menstrual period

1. Severe abdominal pain, possibility of fallopian tube rupture with intraperitoneal hemorrhage with possible death.

Slide #1 [Robbins fig 24-54] frequent locations of ectopic pregnancy—fallopian tube, intrauterine portion of fallopian tube, attached to the ovary, and free-floating in the abdomen

IV. Twins …"you know, if one is not good enough they're twins"

A.  Monozygotic—division of one fertilized ovum, or dizygotic—fertilization of two ova.

B.  Slide #1 [Robbins fig 24-56]

1. Diamniotic, Dichorionic—2 amnions & 2 chorions, can be one placental disk or two separate disks, always dizygotic

2. Diamniotic, Monochorionic—2 amnions & one chorion, if it's monochorionic the twins can be identical

3. Monoamniotic, Monochorionic—1 amnion & 1 chorion, sibling rivalry sets in and can result in umbilical entanglement

Illustration of dividing membrane

Slide # 2 gross, diamniotic, monochorionic: one patty with two cords, the dividing membranes are shiny. "If you can read your newspaper through the dividing membranes it's most likely diamnionic, monochorionic.

Slide #3 micro, diamniotic, dichorionic non-fused: look at the dividing membrane, you see separate amnion and chorion for each twin

Slide #4, micro, diamniotic, dichorionic fused: same as #3 but the chorions stick together

Slide #5 micro, diamniotic, monochorionic: two amnions seen, with one chorion over them. Cannot see anything between the amnions

Slide #6 micro, monoamniotic, monochorionic

Slide #7 gross, monoamniotic, monochorionic: umbilical cords may become entangled, loss of blood supply as one cord strangles the other

C. Slide #8 gross, diamniotic, monochorionic: may have vascular anastamoses (present in 15-35%) that can lead to unequal blood distribution between twins = twin-to-twin transfusion

1. Most of the time both twins are fine, however unequal distribution can occur

2. Occurs only in monochorionic twins

3. Clinically, may not be very apparent or can result in the death of both babies

Slide #9 gross, twin-to-twin transfusion syndrome: section of placenta: one part (recipient of blood) is thick and healthy while the other part (donor of blood) looks pale and shrunken

Slide#10 #11 gross, twin-to-twin transfusion syndrome: donor is smaller, less healthy; organs of recipient are much better developed, may be congested (heart, lungs, liver, spleen, adrenals, and kidney of donor are pale and shrunken) [also see Robbins fig 24-57]

Slide#12 gross, quadrupled placenta

V. Inflammation & Infections

A. Ascending infection

1. Most common route of infection

2. Spreads up through the birth canal

3. Most often bacterial

4. Effects placental membranes, leading to:

Chorioamnionitis: may lead to premature rupture of membranes (premature labor)

Funisitis: "This is a cute word" umbilical cord infection occurs after prolonged chorioamnionitis

B. Hematogenous infection

1. Spreads through placental blood supply

2. Leads to inflammation of chorionic villi—villitis

3. Most often viral (TORCH—Toxoplasmosis, Others: syphilis, leptospira etc, Rubella, CMV, & Herpes)

Slide #1 [Robbins fig 24-58] gross, chorioamnionitis: cloudy, purulent, foul smelling placenta with thickened membranes (cannot read newspaper through the membranes)

Slide #2 micro, placental membranes: PMNs from chorion spilling into amniotic epithelium (this is chorioamnionitis, if infection restricted to chorion—chorionitis)

Slide #3 micro, sometimes fetal surface contains many microabscesses (when this is the case think of Listeria)

Slide #4 gross, funisitis: surface of umbilical cord is cloudy; in this case, white plaques are seen (to impress colleagues, you can correctly identify this as Candida infection)

Slide #5 micro, between wall of umbilical vein and Warthin’s jelly: invasion of PMNs

Slide #6 micro, characteristic of candida funisitis: PMNs invade to the surface forming sub-amniotic aggregates

Slide #7 micro, candida invading Warthin’s jelly from the surface

Slide #8 gross, cross section: chronic funisitis: wide rings seen around vessels

Slide#9 micro, villitis: placenta infected through hematogenous route; increased cellularity in villi, lymphocytes present; consider TORCH organisms (in the case of CMV, can see owls eye inclusions; also hydrocephalus and periventricular calcifications by x-ray; kidney effected as well)

VI. Gestational Trophoblastic Disease… "Just something that you'll have to memorize and I'm sorry about that."

A. Hydatiform Mole (HM)

1. Occurs in 1/1000 pregnancies, is more common in the far east

2. Histologically, edematous chorionic villi and trophoblastic proliferation observed, looks like a mass of grapes.

3. Patients present with vaginal bleeding

4. Physical exam reveals uterine enlargement (more than expected per stage of gestation)

5. Patient may notice passage of watery fluid with small grape-like masses of tissue (friable)

Complete mole:

Entire placenta is affected

Hydrops (edematous swelling) of most/all chorionic villi

Diffuse trophoblastic hyperplasia, mainly syncytiotrophoblast

Virtual absence of vessels

No fetal parts

90% are 46 XX diploid: maternal DNA lost, all genetic material derived from(one or two) sperm

10% are 46 XY

2% of complete hydatiform moles give rise to choriocarcinoma

Partial mole:

Not all villi are swollen

Focal trophoblastic proliferation

Fertilization of egg by (one or two sperm) can give triploid or tetraploid karyotype—maternal DNA intact

Presence of fetal parts

Robbins, table 24-5 is a very good comparative summary

Slide #1 [similar to Robbins fig 24-62] gross, complete mole: no “hamburger appearance,” grape-like tissue throughout the placenta; no umbilicus (no fetal parts)

Slide#2 [similar to Robbins fig 24-63b] micro, complete mole: swollen villi, diffuse circumfrential cytotrophoblast proliferation, no blood vessels

Slide#3 gross, partial mole: normal placenta along with grape clusters

Slide#4 gross, partial mole: can see fetal parts

Slide #5 [refer also to Robbins fig 24-63a] micro, partial mole: some proliferation of trophoblasts, swelling of a few villi, some normal villi

B. Invasive Mole

1. Penetrates or perforates the uterine wall

2. Usually local, may embolize to distant sites (lung, brain)

3. Patient presents with vaginal bleeding

4. Physical exam reveals uterine enlargement (larger than expected per gestational age upon abdominal palpation)

Slide#6 [similar to Robbins fig 24-64] gross, mole (grape-like clusters) invading uterine wall

Slide#7 micro, invasive mole

C. Choriocarcinoma: malignant trophoblastic disease

1. Not common: occurs in 1/20000-30000 pregnancies

2. May occur in normal or abnormal pregnancies

50% arise in patients with previous hydatiform moles

25% arise in patients with previous abortions

22% occur in normal pregnancies

3. Malignant neoplasm of trophoblastic cells—abnormal proliferation of cytotrophoblasts & syncytiotrophoblasts

4. Soft, fleshy (yellow-white) tumor with ischemic necrosis and extensive hemorrhage

5. HCG is highly increased

6. Tumor does not produce chorionic villi

7. Rapid local invasion

8. Widely metastasizing (especially to the lungs: metastases may be all that remain of choriocarcinoma if primary tumor has undergone total ischemic necrosis)

9. Patients present with spotting (bleeding) during normal pregnancy, after miscarriage, or after curettage

10. Responds well to chemotherapy

Slide #8 gross [Robbins fig 24-65]

Slide#9 micro[Robbins fig 24-65], syncytiotrophoblasts invading wall of uterus; cytotrophoblasts may be seen

Slide#10 micro, no placental architecture left (no more chorionic villi), invades as sheets of cells

D. Placental Site Trophoblastic Tumor (for completeness sake)

1. Rare

2. Proliferation of intermediate trophoblasts

3. Low HCG

4. Locally invasive—into myometrium