Placental Pathology for the Non Combatant

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Placental Pathology

for the Non-Combatant

Glenn P. Taylor, MD, FRCPC

Division of Pathology, Hospital for Sick Children

Department of Laboratory Medicine and Pathobiology

University of Toronto



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Placental Pathology

for the Non-Combatant

Glenn P. Taylor, MD, FRCPC

Slide Image Collection

Seminar Presented at the Annual Meeting

of

The Ontario Association of Pathologists

May 15, 2004



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Acknowledgements

• Dr. Virginia Baldwin University of British Columbia

• Dr. Fergall Magee BC Children’s and Women’s Hospitals

• Dr. Indrojit Roy St. Mary’s Hospital, Montreal



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Goals and Objectives

1. Understand guidelines for appropriate selection of

placentas for pathologic examination; approach the

examination in a systematic and informative way.

2. Recognize a spectrum of common gross

abnormalities and understand their potential clinical

relevance.

3. Identify some less common lesions that are

associated with significant potential for adverse

pregnancy outcome.



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Outline

Introduction

1. Brief Review of Placental Morphology2. Placental Infections

Chorioamnionitis

Villitis3. Vascular Obstructive Lesions



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Outline

4. Infarcts and Impaired Uteroplacental

Perfusion

5. Perivillous Fibrin6. Placental Hematomas

7. Meconium and Other Staining

8. Twin Placentas

Conclusion



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Brief Morphologic Reviewof the

Third Trimester Placenta



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Relevant Placental Morphology

• selection of placentas for examination

• gross examination and morphology of the

placenta• microscopic features of the third trimester

placenta



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Placental Examination

• audit antenatal clinical judgment/management

• uncover unavoidable or unpredictable factors

• reveal potentially recurrent, preventable or treatable conditions

• suggest risk for short or long-term sequelae to

newborn



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Indications for Placental Examination

Fetal

Maternal Placental



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Maternal Conditions

• hypertension/preeclampsia/eclampsia

• diabetes mellitus

• maternal fever/infection• history of repeated pregnancy losses

• maternal substance abuse

• repetitive vaginal bleeding in pregnancy



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Fetal and Neonatal Conditions

• stillbirth or perinatal death

• multiple birth

• congenital anomalies

• fetal growth restriction

• prematurity (<32 weeks)/post maturity (> 42 weeks)

• fetal hydrops

• admission to NICU/severe CNS depression

• suspected infection



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Placental Conditions

• gross abnormality of membranes, cord, or disk

• suspicion of placental abruption

• oligohydramnios



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Placental Examination

unfixed placenta

• amnion/chorion for cytogenetics• subamniotic swab for bacteriology

• viral cultures

• biochemical and molecular analyses

• vascular injection studies (multiple gestation)

• electron microscopy

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Freeze Artifact - Hemolysis

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Gross Examination of Placenta

• membranes

• cord

• disk – fetal surface

– maternal surface

– parenchyma

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Reflected Membranes

• colour and opacity

– blood and/or meconium staining

• nature of insertion• point of rupture

• other abnormalities

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Umbilical Cord

• length and diameter

• insertion

• vessel number • coiling

• abnormalities

– varices, false knots, and true knots – thromboses and hematomas

– others

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False Knot (Varices)

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Chorionic (Fetal) Surface

• colour and opacity

• surface texture

– amnion nodosum• vascular pattern

• thrombi

• plaques• cysts

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Trimmed Placenta

• weight

• dimensions

• contour • accessory lobes

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AV

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Circumvallate Extrachorialis

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Accessory Lobe

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Basal (Maternal) Surface

• completeness

• contour

– depressions, bulges

• fibrin and calcification

• infarcts

• hematomas

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Parenchyma

• texture and colour

• fibrinoid

• infarcts• thrombi

• cysts

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Microscopic Examination of Placenta

• membrane roll and distal cord section

• fetal and maternal surfaces, proximal cord

section

• 2 - 3 full thickness sections, paracentral

parenchyma

• additional sections from macroscopic lesions

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x 3

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Placenta Histology: Cord

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Umbilical Vein

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Umbilical Artery

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Wharton’s Jelly

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Cord Epithelium SquamousAmnion

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Placenta Histology: Membranes

• amnion

• chorion

• chorion laeve• decidua capsularis

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Membranes

Amnion

Chorion

Decidua

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Amnion and Chorion

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Chorion

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Chorion Laeve

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Decidual (Maternal) Vessels

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Placenta Histology: Disk

• chorionic surface

• chorionic villi

• intervillous space• maternal (basal) surface

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Amnion

Chorion

Trophoblast - Fibrin

Chorionic Surface

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Stem Villous

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Intermediate Villous

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Tertiary Villi

Hofbauer Cells

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Maturation of Chorionic Villi

• increase in numbers of terminal villi

• increase in terminal villous capillaries

• decrease in thickness of the VSM

• decrease in the size of terminal villi

• decrease in prominence of cytotrophoblast cells

• increase of syncytial nuclear aggregates (knots)

• increase of villous fibrinoid

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Early Third Trimester

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Mid Third Trimester

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Late Third Trimester

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Late Third Trimester

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Intervillous Space - Maternal Sickle Cells

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Trophoblast andFibrinoid

Decidua

Maternal Surface

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Decidual (Maternal) Plate

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Placental Infections

Chorioamnionitis

Villitis

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Chorioamnionitis(Ascending Infection)

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Routes of Infection

1. maternal

hematogenous

2. direct from

endometrium

3. ascending decidual

infection

4. ascending amniotic

infection

5. iatrogenic

Fox, Pathology of thePlacenta, 2nd Ed.

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Stage I Stage II Stage III



Intervillous Space

Amniotic Cavity

Amnion

Chorion

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Intervillositis(subchorionitis)

g

Chorionitis

g

Chorioamnionitis

= maternal PMN

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Choriodeciduitis of Reflected Membranes

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Early Chorioamnionitis of Reflected Membranes

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F l R d C



Fetal Response and Consequences

• umbilical cord vasculitis

– funisitis

• chorionic surface vasculitis

– fetal vessel thrombosis

• fetal pneumonia and sepsis

• fetal cerebral injury

– cytokine mediated

– cerebral palsy

• preterm labour and delivery

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Funisitis

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Chorionic Surface Vasculitis

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Ch i i iti Eti l



Chorioamnionitis - Etiology

• culture negative

• Enterococci

• Group B Streptococcus, anerobic Streptoccus

• E. coli and other enteric bacteria

• Fusobacteria

• polymicrobial (”bacterial vaginosis”) – Gardnerella vaginalis, Mycoplasma homins,

Ureaplasma urealyticum, and others)

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Ch i i iti i l



Chorioamnionitis - special cases

• Candida choriamnionitis

• Listeria monocytogenes

• Herpes virus amniotic infection

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Listeria Placentitis

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T k H M



Take Home Messages

• Acute chorioamnionitis (ascending amniotic

infection) is the most common type of

placental infection (in up to 24% of placentas).

• There is poor correlation with microscopicallydiagnosed chorioamnionitis and clinical

chorioamnionitis, microbiology studies,

neonatal consequences, and even gross placental morphology.

• However, significant neonatal sequelae can

occur, especially in the preterm infant.

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Villitis

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Villiti f U k Eti l



Villitis of Unknown Etiology

• 21 years old primigravida mother

• induction of labour at 37 weeks GA for:

– severe intrauterine growth restriction

– non-reassuring fetal heart rhythm strips

• infant weighed 1850 g, placenta 290 g

– placental weight index: 0.157, expected 0.145

• Apgar scores 81 and 95

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Villitis



Villitis

• destructive inflammatory process of chorionic

villi

– maternal hematogenous route

• acute (rare) or chronic (common)

• specific etiology (rare) or unknown (common)

• clinically significant or not

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Villitis of Unknown Etiology



gy

(VUE)

• no etiology identified by clinical, morphological, or microbiological investigations

– diagnosis of exclusion

• 85% of cases

• 3 to 10% of pregnancies

• association with adverse pregnancy outcome

– directly proportional to severity/extent of inflammation

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Histologic Grading of VUE



Histologic Grading of VUE

Focal

< 5 villi/focus

single focus

1 slide only

Multifocal< 5 villi/focus

multiple slides

Diffuse > 5% of terminal villiaffected

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Pathogenesis of VUE



Pathogenesis of VUE

• occult infection

v.s.

• maternal immunological response

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Clinical Associations of VUE



Clinical Associations of VUE

• intrauterine growth restriction

• ↑ maternal serum α-fetoprotein

• intrauterine fetal death

• preterm delivery

• recurrence in subsequent pregnancies

• toxemia

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CMV Immunohistochemicalstaining

courtesy of Dr. S. Viero

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Plasma Cell Villitis



Plasma Cell Villitis

• cytomegalovirus

• toxoplasmosis

• syphilis

• VUE

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Other Specific Villitides



Other Specific Villitides

• varicella/herpes zoster

• herpes simplex

• HIV

• Parvovirus B19

• Listeria monocytogenes

• others…

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Varicella Villitis

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Toxoplasmosis

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Toxoplasmosis

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Basal Chronic Deciduitis/Villitis

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Take Home Messages



Take Home Messages

• Chronic villitis is the most common type of villous inflammation, seen in up to 10% of placentas.

• The most common form is “villitis of unknown etiology,” a condition that should bedocumented because of its significantassociation with pregnancy complications.

• If plasma cells are present, CMV or other specific infectious etiology should be sought.

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ThrombophiliaVascular Obstructive Lesions

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Maternal ThrombophiliaP C l



Pregnancy Complications

• spontaneous abortion


• intrauterine fetal death• severe pre-eclampsia

• abruptio placentae

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Maternal ThrombophiliaPl l P h l



Placental Pathology

• intervillous thrombi

• decidual vessel thrombi

• placental infarcts• fibrinoid necrosis of decidual vessels

– placental abruption

• excessive perivillous fibrin deposition

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Fetal-Side Vascular Obstruction



Fetal Side Vascular Obstruction

• arterial thrombi

– localized or diffuse thrombosis of surface or stem

chorionic villous arteries

– downstream avascular villi

• venous thrombi

– occlusive thrombosis of surface or stem chorionic

villous veins

– intimal fibrin cushions

– “hemorrhagic endovasculopathy”

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Avascular Vili and Perivillous Fibrinoid

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Fetal-Side Arterial ObstructionC



Causes

• antiplatelet antibodies

• anticoagulant factor deficiencies

– protein C – protein S

– antithrombin III

• hypercoagulability states – antiphospholipid antibody syndrome

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Fetal-Side Arterial ObstructionC



Consequences



• hydrops fetalis

• neonatal asphyxia

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Chorionic Vein Thrombosis

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Hemorrhagic Endovasculopathy

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Fetal-Side Venous ObstructionC



Causes

• acute and chronic umbilical cord occlusion

• hydrops fetalis

• maternal diabetes mellitus• antiphospholipid antibody syndrome

• chorioamnionitis with fetal surface vasculitis

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Fetal-Side Venous ObstructionC



Consequences


• perinatal asphyxia

• cerebral injury with cerebral palsy• fetal systemic thromboembolism

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Placental Venous Embolus with Gangrene

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Take Home Messages



g

• Maternal and fetal thrombophilia areassociated with vascular obstructive lesions

and poor pregnancy outcome.

• The thrombophilic states may be recurrent,therefore recognition of obstructive lesions in

the various vascular compartments of the

placenta, and their morphologic consequences,can provide important information for

management of future pregnancies.

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Infarcts, Decidual Vasculopathy

andImpaired Uteroplacental Blood Flow

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Impaired Uteroplacental Perfusion



p p

• mother 32 years of age, hypertensive

• term delivery

• placenta 380 g

– 2 peripheral and 3 central discrete parenchymal

lesions

• 15% of placental volume

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Placental Infarct

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Decidual Vasculopathy

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Placental Infarcts

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Placental Infarcts: Pathogenesis



• impaired perfusion of intervillous space

– abnormal maternal decidual (spiral) arteries

– separation of villous tissue from decidual bed(abruption)

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Placental Infarcts



“Normal” Abnormal

peripheral central

single multiple

< 1.0 cm diameter > 1.0 cm diameter

term placenta premature placenta

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• fibrin deposition

• atherosis

• thrombosis

• fibrosis

• failure of adaptive changes in decidua basalis

arteries

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“Adapted” Spiral Artery

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Impaired Uteroplacental Perfusion



• Tenney-Parker changes – exaggerated syncytial knots

– small, fibrotic villi

• infarcts

• intervillous thrombi

• placental abruption

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Tenney-Parker Changes

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24 week GA



Severe Maternal PIHNormal

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30 weeks GA - Accelerated Villous Maturation

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Take Home Messages



• A small infarct at the periphery of a term placenta is common and probablyinsignificant.

• However, multiple infarcts, central infarcts,large infarcts, or infarcts in premature placentas are markers for significant maternalvascular disease, especially hypertension.

• They are associated with significant risk for adverse pregnancy outcome.

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Perivillous Fibrin(oid)

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Excessive Perivillous Fibrinoid



• diffuse massive perivillous fibrin(oid) – Gitterinfarkt

– > 20% of terminal villi encased in fibrin

• maternal floor infarct – excessive basal fibrinoid deposition forming a

thick “rind” up to 2 cm deep

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Excessive Perivillous FibrinoidCauses/Associations



Causes/Associations

• unkown

• stasis of intervillous space

– maternal vascular disease

• antiphospholipid antibodies

• maternal hypercoagulable state

• severe chronic villitis

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Perivillous Fibrinoid

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Perivillous Fibrin

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Chronic Villitis and Perivillous Fibrin

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InfarctPerivillous Fibrinoid

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Maternal Floor Infarct

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Maternal Floor Infarct

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Massive Perivillous Fibrinoid

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Excessive Perivillous FibrinoidConsequences



q

• placenta small for gestational age

• severe early intrauterine growth restriction

• intrauterine fetal death (up to 50%)• preterm delivery

• miscarriage

• recurrence in subsequent pregnancies (20%)

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Take Home Messages



• There is a strong association of massive perivillous fibrinoid deposition and poor

pregnancy outcome.

• Identification of this pathology has importantconsequences for prognosis and management

of future pregnancies of the affected mother.

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Placental Hematomas

andPlacental Abruption

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Placental Abruption



• 27 years old primigravida mother • delivery induced at 34 weeks GA for PROM of

1 week and maternal fever

• placenta weighed 420 g, infant weight notreported

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Abruptio Placentae



clinical obstetrical syndrome• acute abdominal pain

• abdominal rigidity and tenderness

• per vaginal bleeding

premature separation of the placenta

retroplacental hematoma

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Abruption Morphology: Classic



• maternal surface large laminated blood clot – degenerating/organizing

• compression of adjacent placental villous

parenchyma

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Abruption Morphology: Acute



• non-organized blood clot +/- adherent• decidual hemorrhage, necrosis, inflammation

• intravillous hemorrhage of adjacent villous

parenchyma

• infarction of adjacent villous parenchyma

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Causes of Placental Abruption



• maternal hypertension• preeclampsia/eclampsia

• HELLP syndrome

• lupus anticoagulant

• anticardiolipin syndrome

• systemic lupus

erythematosus

• decidual arteriopathy

• maternal diabetes mellitus

• cigarette smoking

• cocaine use

• maternal abdominal trauma

(i.e., MVA)• complication of amniocentesis

• abnormal uterine structure

• chorioamnionitis

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Take Home Messages



• Retroplacental hematoma is associated withsignificant fetal morbidity and mortality and

with several important maternal disorders.

• Morphologic confirmation of an acute placental abruption may be difficult, but there

are some gross and microscopic clues to help

distinguish delivery-associated clot from true

retroplacental hematoma.

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Meconium and Other Staining

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Intrauterine Meconium Discharge



• primigravida 26 years old mother • labour at 41 weeks GA

• emergency Cesarean section for FHR of 50/

min• thick meconium covered placenta

• Apgar scores 11 and 810

– first cord pH 6.83

• placenta weighed 365 g

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Conditions Seen with Meconium



• placental abruption• umbilical cord compression

• large fetomaternal hemorrhage

• maternal floor infarction

• post maturity

• chorioamnionitis

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Meconium Toxicity



• Amnion – degeneration

– necrosis

– ulceration• Umbilical and Chorionic Surface Vessels

– vasospasm

– medial myocyte degeneration – segmental inflammation

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Amniotic Edema

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Normal Amnion Meconium Exposure

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Meconium “venulitis”

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Myocyte Degeneration

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Timing of Meconium Staining



meconium in

amniotic

macrophages

1 hour

meconium in

chorion4 to 6 hours

meconium in

decidua “several” hours

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Meconium: Clinical Correlates



Gross Features

• green slimy staining (acute)

• slippery, edematous, dark

membranes (subacute)

• dull, diffuse, muddy

staining (chronic)

Clinical Outcome

• usually normal

• high risk for

– meconium aspiration– perinatal asphyxia

– cerebral palsy

• some infants have CNS

deficits

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Hemosiderin

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Amnion-Chorion Hemosiderin



• Subchorionic Thrombi• Marginal Premature Separation (abruption)

• Decidual Necrosis

• Chorionic Surface Vessel Bleeding

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Take Home Messages



• Passage of meconium in utero is not normal, but becomes more “normal” towards term.

• There is a positive association with poor pregnancy

outcome and meconium passage in earlier gestation

and in post mature pregnancies.

• Subacute and chronic meconium exposure has

stronger association with bad outcome than does

acute discharge. These can be distinguishedmorphologically.

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Single Disk Twin Placenta

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Twin Births



• Caucasian population – 1:80 births

– ~ 30% monozygous (identical)

– ~ 70% dizygous (fraternal)• Black Americans

– 1:70 births

– Noruba in Nigeria 1:20 births

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Monozygotic Twin Placentae



courtesy of Dr. Virginia Baldwin

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Monochorionic-DiamnioticDichorionic-Diamniotic

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Dichorionic-Diamniotic

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Monochorionic-Diamniotic

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Monchorionic Twin Placenta



• Monochorionic-Diamniotic – premature labour and delivery

– twin-twin transfusion syndrome (~15%)

• chronic/acute – polyhydramnios

– shared autolytic products of a dead twin

• Monochorionic-Monoamniotic – as above

– cord entanglement

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Recipient TwinDonor Twin

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Fetus Papyraceusacardiac

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Monochorionic-Monoamniotic

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Take Home Messages



• The nature of the separating membranes in asingle disk twin placenta provides a good

indication of zygosity and the potential for

problems with the twin pregnancy.

• Monochorionic placentas have shared vascular

domains, which can cause significant in utero

or perinatal adverse events. Documentation of

the extent and nature of the vascular

anastomoses requires examination of the

placenta in the fresh state.

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Conclusion: Placental Pathology for the Non-Combatant



this presentation aimed to provide guidance on

• when to look for placental pathology

• how to investigate placental pathologyand

• what placental pathology might be important

Dr. G. Taylor

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Placental Pathology for the Non Combatant