PLACENTA LECTURE 1

Michael K Fritsch MD, PhD Northwestern University and Ann and Robert H. Lurie Childrens Hospital of Chicago

Dr. J. W. Ballantyne:

Maternal-Fetal-Placental Unit

a diseased fetus without its placenta is an imperfect specimen and a description of a fetal malady, unless accompanied by a notice of the placental condition is incomplete During intrauterine life, the fetus, the membranes, the cord and placenta form an organic whole and disease of any part must react upon and affect the other. Ballantyne, JW: Disease and Deformities of the Foetus: An Attempt to a System of Antenatal Pathology. Edinburgh, Oliver and Boyd, 1892-1895.

From DB Singer

GOALS Placenta Lecture 1

Placental development. Review normal histology. Review gross pathology of placenta, membranes, and umbilical cord.

PLACENTAL DEVELOPMENT

Early Embryonic Development (Differentiation)

Modified from Keller G. Genes & Development 19:1129-1155, 2005

Early Placental Development Day 7.5

From: Langmans Medical Embryolgy 11th ed. TW Sadler

Early Placental Development Day 9

Embryonic Pole

From: Langmans Medical Embryolgy 11th ed. TW Sadler

Early Placental Development Day 13

1 Completely embedded in endometrial stroma. 2 - Lacunae open into maternal spiral arteries sinusoids. Uteroplacental circulation established. 3 Extraembryonic mesoderm layer forms and lines the cytotrophoblast layer (to become chorion). 4 Amnionblast (derived from epiblast) will form separate layer amnion later. 5 Connecting stalk will become UC. 6 Primary villi form. 7 chorionic cavity forms.

From: Langmans Medical Embryolgy 11th ed. TW Sadler

VASCULOGENESIS OF THE PLACENTA (Beginning day 14)

New vessels formed from mesodermic mesenchyme.

Cytotrophoblast cells invade through syncytiotrophoblast and results in altered differentiation of extravillous trophoblast (EVT).

EVT

From: Langmans Medical Embryolgy 11th ed. TW Sadler

Villous Development 4th w 4th m

Archoring (primary) villi.

Branching to secondary and tertiary villi.

From: Langmans Medical Embryolgy 11th ed. TW Sadler

Formation of Membranes 8w 12 w

From: Langmans Medical Embryolgy 11th ed. TW Sadler

Formation of the Umbilical Cord

10 w 5w

From: Langmans Medical Embryolgy 11th ed. TW Sadler

NORMAL PLACENTAL HISTOLOGY

Placenta Review 3

1 2
The Developing Human by Moore & Persaud

Membranes

Decidua

Extravillous Trophoblast Amnion

Chorion

Chorionic Plate
Amnion
Amnion Epithelium Compact layer Amnion mesoderm

Chorion with fetal vessels

Chorion

Few trophoblast stem cells Langhans fibrinoid Invasive cytotrophoblast Syncytiotrophoblast Intervillous space

Villi and Intervillous space

Basal Plate

Decidua Nitabuchs Fibrinoid

Rohrs Fibrinoid Extravillous Trophoblast Villi

Term Villi

PLACENTAL PATHOLOGY

Why examine the placenta? Pros: Many neonatal diseases are associated with placental pathology. Placental pathology can give some insight into outcome. Prediction for future pregnancy outcomes. Cons: High false positive findings in placenta. Many normal neonates may have pathology in their placentas. Pathology findings are not necessarily disease specific. False negative findings not as great, but still significant. Fetuses with pathology may have a normal placenta. Skill and efforts of pathologists vary tremendously.

Fetal Outcomes Associated with Singleton Placental Pathology

1) 2) 3) 4) 5) 1) 2)

Normal Preterm delivery (spontaneous abortion) Fetal growth restriction (SGA - IUGR) Hypoxic/ischemic CNS injury Infection Death (stillbirth) Others (syndromes, tumors, gestational trophoblastic disease, recurrence, etc)

When does a placenta get sent to a pathologist?

CAP guidelines (1997) and each hospital to establish their criteria based on above.
From Embryo and Fetal Pathology by E. Gilbert-Barness

SUMMARY

AFIP Placental Pathology by Kraus et al. 2004

GROSS PLACENTAL PATHOLOGY

Placenta Review

Normal: Size (at term) 450-630 gm, 15-25 cm in diameter, up to 3 cm thick, ovoid to round, single lobe with 15-20 cotelydons. Membranes Clear and inserted at margins. Placenta Parenchyma beefy red without lesions. Chorionic plate clear with uniformly sized surface vessels. Umbilical cord Eccentric insertion of 3 vessel cord, 1-2 cm in thickness. Uniformly white surface and Whartons jelly.

SIZE AND SHAPE

SHAPE ACCESSORY LOBES

Accessory Lobe

MultilobedPlacenta
1 5% 2 membrane vessels 3 increased risk for: - bleeding - placenta previa - retained placenta

Succenturiate (Multilobed) Placenta

From DB Singer

SIZE
LGA (>10%) due to diabetes, hydrops, mesenchymal dysplasia, infections (syphilis), maternal obesity, genetic, others. SGA (<10%) due to MVU (HTN, preeclampsia, infarcts), MPVFD/MFI, maternal chronic disease, chronic villitis, severe fetal thrombotic vasculopathy, genetic, others.

WEIGHT (GM)

FETUS

PLACENTA

GESTATIONAL AGE (WEEKS)

From DB Singer

MEMBRANES & CHORIONIC PLATE

Circumvallate Membrane Insertion

Cicumvallate ridge present associated with increased risk of bleeding and premature delivery. Circummarginate no ridge (common 25%) significance uncertain. We report both as % of circumference involved and widest amount of extrachorialis (cm).
From DB Singer

Membranes with remote parietal hemorrhages with hemosiderin.

When extensive consider the diagnosis of diffuse chorioamniotic hemosiderosis.

Subchorionic Hemorrhages and Fibrin Thrombi

Subchorionic Fibrin Thrombus

Common 60% Associated with preterm birth, abortion, vaginal bleeding, IUGR, fetal demise. Frequent in placentas from mothers with severe heart disease or thrombophilia.

Subchorionic Acute Hemorrhage Associated with Amniotic Fluid Infection

SquamousMetaplasiaofAmnion

From DB Singer

SquamousMetaplasia

From DB Singer

AmnionNodosum (Oligohydramnios&Decreased Movement)

From DB Singer

AmnionNodosum

From DB Singer

Fetus Papyraceous

Fetus Papyraceous

SUBCHORIONIC CYST

BASAL PLATE & PARENCHYMA

Hemorrhages including abruption

Retroplacental and Marginal Hemorrhages AbruptionwithVaginalHemorrhage

Abruptions (1-4%) are clinically significant retroplacental/marginal hemorrhages.

From DB Singer

MarginalAbruption

From DB Singer

Low Implantation- Praevia

From DB Singer

Central Abruption

From DB Singer

CentralAbruption

Adherent central clot 3.4 cm Adherent marginal clot 2.4 cm

Retroplacental & marginal acute to subacute hemorrhages with intraparenchymal extension consistent with the clinical history of abruption.

Compression of intervillous space near hemorrhages.

MARGINAL HEMORRHAGE/ABRUPTION IN AFI

ChronicAbruption

From DB Singer

Summary Retroplacental and Marginal Hemorrhages: 1 Do not correlate well with abruption (separation of basal plate from uterine wall due to intervening hemorrhage). 2 Clinically significant (true abruption) acute hemorrhages associated with adverse outcomes: preterm delivery, IUGR, stillbirth, CNS injury. 3 Etiologies MVU, trauma, amniocentesis, uterine anomalies, placenta previa, cocaine use, nicotine, multiparity. 4 Clinical triad vaginal bleeding, pain, rigid abdomen. 5 Histologic criteria: < 1h maybe nothing Acute (hours to a few days) compression of villi and loss of intervillous spaces, increased perivillous fibrin focally, acute hemorrhage with neutrophils, associated decidual necrosis (arterial). Chronic (days to weeks) above with infarcted villi, and hemosiderin (venous). Associated with multiparity, smoking, oligohydramnios, and deep implantation, circumvallate insertion, preterm delivery, CP, neurologic impairment.

Intervillous Thrombus Common (20%). Nonspecific. Associated with FMH, maternal thrombophilias, and preeclampsia. Usually fetal blood.

Intervillous Thrombi

Villous Infarcts

Due to diminished maternal perfusion with ischemic necrosis of affected villi. Associated with HTN and preeclampsia (MVU). Histologic findings: Early Loss of intervillous space and villous crowding. Increased perivillous fibrin. Acute inflammation. Later Loss of nuclear basophilia. Ghosted villi +/- surrounding fibrin. Calcification. Surrounding villi with DVH and increased syncytial knots.

Adverse outcomes: IUGR, small placenta, death (>50% placenta infarcted).

Placental Infarcts

From DB Singer

Acute Infarct with Inflammation

Remote Infarct with DVH and SK

Chorangioma

Benign neoplasm of fetal capillaries. Associated with multiple gestations and congenital anomalies. Grossly: a bulging white or red mass. Histology: Proliferating fetal blood vessels (capillaries) with a cellular stroma. Adverse outcomes: Rare unless large. Fetal hydrops, stillbirth, IUGR, anemia, thrombocytopenia, CHF, abruption, premature delivery, preeclampsia.

Chorangioma with fibrosis

From DB Singer

CHORANGIOMA

CHORANGIOMA

UMBILICAL CORD PATHOLOGY

Insertion Pathology:

Marginal (<1cm from margin): 7%; ? Clinical significance associated with Preterm labor, neonatal asphyxia, abortions, malformed infants. Velamentous (into membranes): 1% singleton (> in twins); prone to trauma, rupture, compression, thrombosis; associated with fetal thrombotic vasculopathy, low birth weight, low Apgar, abnormal fetal heart rate patterns, prematurity, cerebral palsy, early abortion, congenital anomalies, and death. Furcate (vessels leave Whartons jelly before insertion): most normal, but weak association with stillbirth, thrombosis of fetal vessels, IUGR & hemorrhage.

Marginal Insertion

198 GM (23 W 133-211 GM) Marginal insertion 3v UC

Marginal and Velamentous Insertion

VelamentousCordInsertion

From DB Singer

VelamentousCordwithRuptured Vessel

From DB Singer

Marginal and Furcate Insertion

Coiling Pathology: Normal: 1-3 twists (coils) per 10cm of cord. Hypercoiled: >3 twists/10cm Undercoiled: <1twist/10cm Both associated with increased risk of IUGR, fetal distress and perinatal death.

Marginal Insertion of Hypercoiled UC with Meconium

Hypercoiled UC with Partial Loss of Whartons Jelly

UNDERCOILED 2 VESSEL UC

Length: Normal at term: 60 +/- 13 cm. Excessively long cords (5%) are associated with cord accidents (stillbirth), entanglements, cord prolapse, true knots, excessive coiling, constricture, thrombi. Associated adverse outcomes include fetal distress, neurologic impairment, IUGR and IUFD. Abnormally short cords (1-2%) are associated with cord hemorrhages, abruption, failure of descent, fetal distress, low Apgar, & congenital anomalies.

LongandHypercoiledCord

From DB Singer

Number of UC vessels: Single umbilical artery (2 vessel cord) occurs in 1% of singleton pregnancies. Most outcomes completely normal. Associated increased risk of IUGR, antepartum hemorrhage, polyhydramnios and oligohydramnios. Increased SUA in mothers with diabetes. In autopsy studies SUA is associated with increased likelihood of other congenital anomalies. Accessory vessels: aberrant right umbilical vein or vitelline vessels.

NORMAL UMBILICAL CORD SINGLE UMBILICAL ARTERY

Knots: Rare < 1%. Classify as tight or loose. Tight knots can result in umbilical vein compression. Tight knots associated with increased risk of IUFD and intrapartum demise (up to 10%) and poor neurologic outcome.

True Knot (Tight)

Double True Knot

False Knots (varices)

From DB Singer

Salzburg Austria