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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 of The Ontario Association of Pathologists May 15, 2004

Acknowledgements
Dr. Virginia Baldwin University of British Columbia Dr. Fergall Magee BC Childrens and Womens Hospitals Dr. Indrojit Roy St. Marys 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 Morphology 2. Placental Infections
Chorioamnionitis Villitis

3. Vascular Obstructive Lesions

Outline
4. Infarcts and Impaired Uteroplacental Perfusion 5. Perivillous Fibrin 6. Placental Hematomas 7. Meconium and Other Staining 8. Twin Placentas Conclusion

Brief Morphologic Review of 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

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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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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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x3

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Placenta Histology: Cord

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Umbilical Vein

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Umbilical Artery

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Whartons Jelly

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Amnion

Cord Epithelium

Squamous

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Placenta Histology: Membranes

amnion chorion chorion laeve decidua capsularis

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Amnion Chorion

Decidua

Membranes

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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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Chorionic Surface
Amnion

Chorion

Trophoblast - Fibrin

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Stem Villous

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Intermediate Villous

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Hofbauer Cells

Tertiary Villi

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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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Maternal Surface

Trophoblast and Fibrinoid

Decidua

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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 the Placenta, 2nd Ed.

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Stage I
Intervillositis (subchorionitis) Amniotic Cavity Amnion

Stage II
Chorionitis

Stage III
Chorioamnionitis

Chorion

Intervillous Space

= maternal PMN

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Choriodeciduitis of Reflected Membranes

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Early Chorioamnionitis of Reflected Membranes

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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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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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Chorioamnionitis - special cases

Candida choriamnionitis Listeria monocytogenes Herpes virus amniotic infection

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Listeria Placentitis

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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 microscopically diagnosed 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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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
destructive inflammatory process of chorionic villi
maternal hematogenous route

acute (rare) or chronic (common) specific etiology (rare) or unknown (common) clinically significant or not

Villitis of Unknown Etiology (VUE)

no etiology identified by clinical, morphological, or microbiological investigations
diagnosis of exclusion

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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

Focal < 5 villi/focus single focus 1 slide only < 5 villi/focus multiple slides > 5% of terminal villi affected

Multifocal Diffuse

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Pathogenesis of VUE
occult infection
v.s.

maternal immunological response

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Clinical Associations of VUE

intrauterine growth restriction maternal serum -fetoprotein intrauterine fetal death preterm delivery recurrence in subsequent pregnancies toxemia

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CMV Immunohistochemical staining courtesy of Dr. S. Viero

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Plasma Cell Villitis

cytomegalovirus toxoplasmosis syphilis
VUE

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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

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 be documented because of its significant association with pregnancy complications. If plasma cells are present, CMV or other specific infectious etiology should be sought.

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Thrombophilia Vascular Obstructive Lesions

Maternal Thrombophilia Pregnancy Complications

spontaneous abortion intrauterine growth restriction intrauterine fetal death severe pre-eclampsia abruptio placentae

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Maternal Thrombophilia Placental Pathology

intervillous thrombi decidual vessel thrombi placental infarcts fibrinoid necrosis of decidual vessels
placental abruption

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excessive perivillous fibrin deposition

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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

Fetal-Side Arterial Obstruction Causes

antiplatelet antibodies anticoagulant factor deficiencies
protein C protein S antithrombin III

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hypercoagulability states
antiphospholipid antibody syndrome

Fetal-Side Arterial Obstruction Consequences

intrauterine growth restriction intrauterine fetal death hydrops fetalis neonatal asphyxia

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Chorionic Vein Thrombosis

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Hemorrhagic Endovasculopathy

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Fetal-Side Venous Obstruction 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 Obstruction Consequences

intrauterine fetal death 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

Maternal and fetal thrombophilia are associated 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 Impaired Uteroplacental Blood Flow

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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

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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
peripheral single < 1.0 cm diameter term placenta

Abnormal
central multiple > 1.0 cm diameter premature placenta

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Decidual Vasculopathy
fibrin deposition atherosis thrombosis fibrosis

failure of adaptive changes in decidua basalis arteries

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Adapted Spiral Artery

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Decidual Vasculopathy

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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

Normal

Severe Maternal PIH

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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 probably insignificant. However, multiple infarcts, central infarcts, large infarcts, or infarcts in premature placentas are markers for significant maternal vascular 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

Excessive Perivillous Fibrinoid Causes/Associations

unkown stasis of intervillous space
maternal vascular disease

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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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Perivillous Fibrinoid

Infarct

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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 Fibrinoid Consequences

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 important consequences for prognosis and management of future pregnancies of the affected mother.

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Placental Hematomas
and

Placental 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 not reported

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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 with significant 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 meconium in chorion meconium in decidua

1 hour 4 to 6 hours several hours

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Meconium: Clinical Correlates

Gross Features
green slimy staining (acute) slippery, edematous, dark membranes (subacute)

Clinical Outcome
usually normal high risk for meconium aspiration perinatal asphyxia cerebral palsy some infants have CNS deficits

dull, diffuse, muddy staining (chronic)

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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 distinguished morphologically.

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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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Dichorionic-Diamniotic

Monochorionic-Diamniotic

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Dichorionic-Diamniotic

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Dichorionic-Diamniotic

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Dichorionic-Diamniotic

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Monochorionic-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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Donor Twin

Recipient Twin

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Monochorionic-Diamniotic

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Fetus Papyraceus acardiac

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Monochorionic-Monoamniotic

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Take Home Messages

The nature of the separating membranes in a single 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 pathology
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what placental pathology might be important

Dr. G. Taylor

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Orcinus Orca