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

Placental Pathology

for the Non-Combatant

Glenn P. Taylor, MD, FRCPC

Slide Image Collection

Seminar Presented at the Annual Meeting

The Ontario Association of Pathologists

May 15, 2004

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

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.

Outline

Introduction

1. Brief Review of Placental Morphology2. Placental Infections

Chorioamnionitis

Villitis3. Vascular Obstructive Lesions

Outline

4. Infarcts and Impaired Uteroplacental

Perfusion

5. Perivillous Fibrin6. Placental Hematomas

7. Meconium and Other Staining

8. Twin Placentas

Conclusion

Brief Morphologic Reviewof the

Third Trimester Placenta

Relevant Placental Morphology

• selection of placentas for examination

• gross examination and morphology of the

placenta• microscopic features of the third trimester

placenta

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

Indications for Placental Examination

Maternal Placental

Maternal Conditions

• hypertension/preeclampsia/eclampsia

• diabetes mellitus

• maternal fever/infection• history of repeated pregnancy losses

• maternal substance abuse

• repetitive vaginal bleeding in pregnancy

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

Placental Conditions

• gross abnormality of membranes, cord, or disk

• suspicion of placental abruption

• oligohydramnios

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

Freeze Artifact - Hemolysis

Gross Examination of Placenta

• membranes

• cord

• disk – fetal surface

– maternal surface

– parenchyma

Reflected Membranes

• colour and opacity

– blood and/or meconium staining

• nature of insertion• point of rupture

• other abnormalities

Umbilical Cord

• length and diameter

• insertion

• vessel number • coiling

• abnormalities

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

– others

False Knot (Varices)

Chorionic (Fetal) Surface

• colour and opacity

• surface texture

– amnion nodosum• vascular pattern

• thrombi

• plaques• cysts

Trimmed Placenta

• weight

• dimensions

• contour • accessory lobes

Circumvallate Extrachorialis

Accessory Lobe

Basal (Maternal) Surface

• completeness

• contour

– depressions, bulges

• fibrin and calcification

• infarcts

• hematomas

Parenchyma

• texture and colour

• fibrinoid

• infarcts• thrombi

• cysts

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

Placenta Histology: Cord

Umbilical Vein

Umbilical Artery

Wharton’s Jelly

Cord Epithelium SquamousAmnion

Placenta Histology: Membranes

• amnion

• chorion

• chorion laeve• decidua capsularis

Membranes

Amnion

Chorion

Decidua

Amnion and Chorion

Chorion

Chorion Laeve

Decidual (Maternal) Vessels

Placenta Histology: Disk

• chorionic surface

• chorionic villi

• intervillous space• maternal (basal) surface

Amnion

Chorion

Trophoblast - Fibrin

Chorionic Surface

Stem Villous

Intermediate Villous

Tertiary Villi

Hofbauer Cells

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

Early Third Trimester

Mid Third Trimester

Late Third Trimester

Intervillous Space - Maternal Sickle Cells

Trophoblast andFibrinoid

Decidua

Maternal Surface

Decidual (Maternal) Plate

Placental Infections

Chorioamnionitis

Villitis

Chorioamnionitis(Ascending Infection)

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.

Stage I Stage II Stage III

Intervillous Space

Amniotic Cavity

Amnion

Chorion

Intervillositis(subchorionitis)

Chorionitis

Chorioamnionitis

= maternal PMN

Choriodeciduitis of Reflected Membranes

Early Chorioamnionitis of Reflected Membranes

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

Funisitis

Chorionic Surface Vasculitis

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)

Ch i i iti i l

Chorioamnionitis - special cases

• Candida choriamnionitis

• Listeria monocytogenes

• Herpes virus amniotic infection

Listeria Placentitis

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.

Villitis

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

Villitis

• destructive inflammatory process of chorionic

– maternal hematogenous route

• acute (rare) or chronic (common)

• specific etiology (rare) or unknown (common)

• clinically significant or not

Villitis of Unknown Etiology

• 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

Histologic Grading of VUE

< 5 villi/focus

single focus

1 slide only

Multifocal< 5 villi/focus

multiple slides

Diffuse > 5% of terminal villiaffected

Pathogenesis of VUE

• occult infection

• maternal immunological response

Clinical Associations of VUE

• intrauterine growth restriction

• ↑ maternal serum α-fetoprotein

• intrauterine fetal death

• preterm delivery

• recurrence in subsequent pregnancies

• toxemia

CMV Immunohistochemicalstaining

courtesy of Dr. S. Viero

Plasma Cell Villitis

• cytomegalovirus

• toxoplasmosis

• syphilis

• VUE

Other Specific Villitides

• varicella/herpes zoster

• herpes simplex

• HIV

• Parvovirus B19

• Listeria monocytogenes

• others…

Varicella Villitis

Toxoplasmosis

Basal Chronic Deciduitis/Villitis

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.

ThrombophiliaVascular Obstructive Lesions

Maternal ThrombophiliaP C l

Pregnancy Complications

• spontaneous abortion

• intrauterine fetal death• severe pre-eclampsia

• abruptio placentae

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

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”

Avascular Vili and Perivillous Fibrinoid

Fetal-Side Arterial ObstructionC

Causes

• antiplatelet antibodies

• anticoagulant factor deficiencies

– protein C – protein S

– antithrombin III

• hypercoagulability states – antiphospholipid antibody syndrome

Fetal-Side Arterial ObstructionC

Consequences

• hydrops fetalis

• neonatal asphyxia

Chorionic Vein Thrombosis

Hemorrhagic Endovasculopathy

Fetal-Side Venous ObstructionC

Causes

• acute and chronic umbilical cord occlusion

• hydrops fetalis

• maternal diabetes mellitus• antiphospholipid antibody syndrome

• chorioamnionitis with fetal surface vasculitis

Fetal-Side Venous ObstructionC

Consequences

• perinatal asphyxia

• cerebral injury with cerebral palsy• fetal systemic thromboembolism

Placental Venous Embolus with Gangrene

Take Home Messages

• 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.

Infarcts, Decidual Vasculopathy

andImpaired Uteroplacental Blood Flow

Impaired Uteroplacental Perfusion

• mother 32 years of age, hypertensive

• term delivery

• placenta 380 g

– 2 peripheral and 3 central discrete parenchymal

lesions

• 15% of placental volume

Placental Infarct

Decidual Vasculopathy

Placental Infarcts

Placental Infarcts: Pathogenesis

• impaired perfusion of intervillous space

– abnormal maternal decidual (spiral) arteries

– separation of villous tissue from decidual bed(abruption)

Placental Infarcts

“Normal” Abnormal

peripheral central

single multiple

< 1.0 cm diameter > 1.0 cm diameter

term placenta premature placenta

• fibrin deposition

• atherosis

• thrombosis

• fibrosis

• failure of adaptive changes in decidua basalis

arteries

“Adapted” Spiral Artery

Impaired Uteroplacental Perfusion

• Tenney-Parker changes – exaggerated syncytial knots

– small, fibrotic villi

• infarcts

• intervillous thrombi

• placental abruption

Tenney-Parker Changes

24 week GA

Severe Maternal PIHNormal

30 weeks GA - Accelerated Villous Maturation

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.

Perivillous Fibrin(oid)

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

Excessive Perivillous FibrinoidCauses/Associations

Causes/Associations

• unkown

• stasis of intervillous space

– maternal vascular disease

• antiphospholipid antibodies

• maternal hypercoagulable state

• severe chronic villitis

Perivillous Fibrinoid

Perivillous Fibrin

Chronic Villitis and Perivillous Fibrin

InfarctPerivillous Fibrinoid

Maternal Floor Infarct

Massive Perivillous Fibrinoid

Excessive Perivillous FibrinoidConsequences

• placenta small for gestational age

• severe early intrauterine growth restriction

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

• miscarriage

• recurrence in subsequent pregnancies (20%)

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.

Placental Hematomas

andPlacental Abruption

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

Abruptio Placentae

clinical obstetrical syndrome• acute abdominal pain

• abdominal rigidity and tenderness

• per vaginal bleeding

premature separation of the placenta

retroplacental hematoma

Abruption Morphology: Classic

• maternal surface large laminated blood clot – degenerating/organizing

• compression of adjacent placental villous

parenchyma

Abruption Morphology: Acute

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

• intravillous hemorrhage of adjacent villous

parenchyma

• infarction of adjacent villous parenchyma

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

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.

Meconium and Other Staining

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

Conditions Seen with Meconium

• placental abruption• umbilical cord compression

• large fetomaternal hemorrhage

• maternal floor infarction

• post maturity

• chorioamnionitis

Meconium Toxicity

• Amnion – degeneration

– necrosis

– ulceration• Umbilical and Chorionic Surface Vessels

– vasospasm

– medial myocyte degeneration – segmental inflammation

Amniotic Edema

Normal Amnion Meconium Exposure

Meconium “venulitis”

Myocyte Degeneration

Timing of Meconium Staining

meconium in

amniotic

macrophages

1 hour

meconium in

chorion4 to 6 hours

meconium in

decidua “several” hours

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

Hemosiderin

Amnion-Chorion Hemosiderin

• Subchorionic Thrombi• Marginal Premature Separation (abruption)

• Decidual Necrosis

• Chorionic Surface Vessel Bleeding

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.

Single Disk Twin Placenta

Twin Births

• Caucasian population – 1:80 births

– ~ 30% monozygous (identical)

– ~ 70% dizygous (fraternal)• Black Americans

– 1:70 births

– Noruba in Nigeria 1:20 births

Monozygotic Twin Placentae

courtesy of Dr. Virginia Baldwin

Monochorionic-DiamnioticDichorionic-Diamniotic

Dichorionic-Diamniotic

Monochorionic-Diamniotic

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

Recipient TwinDonor Twin

Fetus Papyraceusacardiac

Monochorionic-Monoamniotic

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.

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

placental pathology for the non combatant

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