Placenta

A placenta (fetal aspect) with attached umbilical cord. (WC/Asturnut)

The placenta feeds the developing baby, breathes for it and disposes of its waste.

The organ is one that seems to be left behind; at least one review suggests it isn't done so well by general pathologists.

Placental pathology redirects to this article.

Clinical

Examination of the placenta

• Most placentas are not examined by a pathologist.

Indications for exam by pathology

Some indications for exam by a pathologist:

• Abnormalities in the:
  1. Fetus:
     • Bad fetal outcome.
     • Suspected or known congenital abnormalities or chromosomal abnormalities.
     • IUGR.
  2. Mother:
     • Infection/suspected infection.
     • Pre-term labour.
     • Maternal disease (e.g. SLE, coagulopathy).
     • Complicated pregnancy (preclampsia, pregnancy induced hypertension, gestational diabetes).
  3. Placenta:
     • Unusual gross characteristics.

A more detailed list is given by Hargitai et al. and Chang.

Most common

Most common reasons for submitting a placenta to pathology:

1. Prematurity.
2. PROM / possible chorioamnionitis.
3. Multiple gestation.

Bleeding in late pregnancy

DDx of bleeding in late pregnancy:

• Placental abruption (most common).
• Placenta previa.
• Vasa previa (fetus losing blood).

Clinical screening tests

Main article: Pregnancy

• PAPP-A - low values seen in aneuploidy.

Abbreviations

• C/S = Caesarean section.
• LSCS = lower segment C-section.
• FTP = failure to progress.
• PROM = premature rupture of membranes.
• PPROM = preterm premature ruptures of membranes.
• IUGR = intrauterine growth restriction.
• IOL = induction of labour.

Normal histology

Villi

Main article: Chorionic villi

This is dealt with in a separate article that also covers the types of trophoblast (cytotrophoblast, syncytiotrophoblast, intermediate trophoblast).

Cord

Omphalomesenteric duct remnant

• AKA vitelline duct.
• Benign embryologic remnant.

Features:

• Duct with benign looking cuboidal epithelium.

Allantoic duct remnant

• Benign embryologic remnant.

Features:

• Duct with benign looking flat epithelium.

Vitelline artery remnant

Features:

• Small artery in the cord.

Membranes

Fetus to mother:

• Amnion - thin layer: one cell layer, basement membrane, connective tissue.
• Cleft - artifactual - empty space.
• Chorion - vascular.
• Decidua (maternal tissue) - may contain obsolete chorionic villi; place to look for hypertensive changes.

Amnion

General:

• Next to fetus, surrounds amniotic fluid, avascular.

Characteristics:

• Characterized by a single layer of cells.
  • Cuboidal/squamoid shape.
  • Eosinophilic cytoplasm.
  • Central nucleus.
• Squamous metaplasia may be seen at cord insertion.
• Basement membrane.
• 'Compact layer'.
• 'Fibroblastic layer'.

Chorion

General:

• Surrounds amnion.

Characteristics:

• Layers:
  • 'Reticular layer' - cellular (inner aspect).
  • 'Pseudo-basemement membrane'.
  • 'Outer trophoblastic layer'.
• Has blood vessels.
• Opposed to "trophoblastic X cells" on side opposite of amnion.
  • Beneath of the "trophoblastic X cells" is decidua (mnemonic NEW = nucleus central, eosinophilic, well-defined cell border), which is maternal tissue.

Note:

• Fibrin deposition may be found deep to the chorion - known as subchorionic fibrin deposition.
  • Gross: subchorionic, white/yellow, laminated, classically has a triangular-shape with the base of triangle parallel to fetal aspect of disc.
    • Arises due to localized stasis of the inter-villous maternal blood.
  • Focal small deposits are considered to be a normal finding - seen in ~15% of cases.
    • The pathologic counterpart of this is perivillous fibrin deposition.

Image:

• Subchorionic fibrin deposition (ijpmonline.org).

Common terms

• Chorionic plate - fetal aspect of placenta.
• Basal plate - maternal aspect of placenta.
  • Has extravillous trophoblast.
  • Place to look for maternal vessels.

Grossing

This is often very quick. The gross is quite important, as some things cannot be diagnosed microscopically.

General

• Dimensions:
  • Disc.
  • Length of cord, diameter of cord.
  • Accessory lobes - dimensions.
    • Two lobes of equal size + cord arises in between = bilobate placenta.
• Mass (weight).
  • Should be done 'trimmed' (cord cut-off, membrane cut-off).
  • Should be done when placenta is "fresh", i.e. not fixed -- as mass tables are based on fresh state.
• Umbilical cord
  • Attachment.
    • Location: central, eccentric, marginal.
      • Marginal attachment assoc. with hypertension
    • Membranous or velamentous (veil-like) insertion.
      • Vessels separate/branch prior to reaching placental disc.
    • Furcate insertion - blood vessels separate before reaching placenta disc/not surrounded by Wharton's jelly - vessels more exposed to trauma (risk for vasa previa).
  • Knots (false vs. true).
    • False knots are nothing to worry about -- look like a knot but aren't really one.
  • Twisting/coiling - 1-3 coils/10 cm is normal.
  • Number of vessels.
    • Normal: 2 arteries, 1 vein.
• Membranes - shiny & translucent - normal (green, opaque/dull - chorioamnionitis).
  • Attachment (insertion): marginal (normal), circummarginate (inside edge), circumvallate (folding on self).
  • Site of rupture - if obvious; low point of rupture suggests low-lying placenta.
• Placental disc.
  • Fetal surface - normal is shinny.
    • Dull in chorioamnionitis.
  • Maternal surface
    • Are the cotyledons intact?
    • Adherent clot?
  • Parenchyma - after sectioning:
    • White vs. red nodules.

Notes:

• Parenchymal nodules - a brief DDx:
  • White: infarct (chronic), thrombi, chorangioma, perivillous fibrin deposition.
  • Red: infarct (acute), thrombi.

Sections

1. Cord two sections.
2. Membranes (rolled), two rolls or more.
3. Cord at insertion + disc.
4. Placenta - full thickness (maternal and fetal surface).
   • Sections should not be taken at the margin of the disc.

Placental membranes

Appearance:

• Normal - shiny.
• Chorioamnionitis - opaque/dull.
• Meconium - green.
• Amnion nodosum - yellow patches.
  • Some describe 'em as white.

Placental mass

It is considered routine to obtain a mass for the placenta. This is usually done when the placenta is fresh and with the membranes and cord trimmed, as most tables of placental mass were created with these parameters.

Placental mass by gestational age:

Gest. Age/Percentile	25%	50%	75%
32 weeks	275 g	318 g	377 g
36 weeks	369 g	440 g	508 g
40 weeks	440 g	501 g	572 g

Linear regression - placental mass-gestational age

Based on the table in the AFIP book one can generate the following regression lines:

	50%	10%	90%
slope (g/week)	21.58088235	19.70588235	25.40196078
y-intercept (g)	-357.4558824	-397.2352941	-366.7254902
Pearson (r)	0.988670724	0.988268672	0.982206408

placental mass = slope x gestational age + intercept

What to remember...

Extrapolated from the linear regression (see above):

• 50% at term = 500 grams.
• 50% at 26 weeks = 200 grams.
• The change in mass/week is approximately linear and equal to 300 grams / 14 weeks ~ 20 grams/week.
• The spread in mass between 10% and 90%, crudely estimated, is 200 grams (for GA=26-40).

Notes:

• Is it required?
  • Sebire and Fox have advocated abandoning the practise of obtaining a placental mass, due to the large number of uncontrolled variables inherent in these measures. Instead, they have advocated using mushy descriptors such as "small", "average" and "large", which require experience in examining the organ.
    • In the context of quality, a measure (even if somewhat flawed) is probably more reproducible and objective than arbitrary descriptors which require experience and a continuing case volume to calibrate.

Placentomegaly

• AKA large placenta.

Associations:

• Maternal diabetes - esp. poorly controlled.
• Maternal anemia/low maternal iron stores.
• Fetal malformations.
• Neoplasms of the placenta, e.g. chorangioma.
• Twin-twin transfusion syndrome.
• Chronic intrauterine infections, e.g. syphilis, toxoplasmosis, cytomegalovirus.

Lame causes of a heavy placenta:

• Dates wrong - error in determining the estimated date of confinement.
• Adherent blood clot.

Comment:

• Most of causes seem to have one thing in common:
  • There is a decreased oxygen delivery to the fetus.

Sign out

PLACENTA, UMBILICAL CORD AND FETAL MEMBRANES, CESAERIAN SECTION:
- LARGE PLACENTA (819 GRAMS -- TRIMMED, POST-FIXATION WEIGHT).
- FETAL MEMBRANES WITHIN NORMAL LIMITS.
- THREE VESSEL UMBILICAL CORD WITHIN NORMAL LIMITS.
- PLACENTAL DISC WITH THIRD TRIMESTER VILLI.

Placental growth restriction

• AKA placenta small for gestational age.
• Small placenta redirects here.

Associations:

• Maternal vascular disease, e.g. hypertension.
• Fetal malformations.

Sign out

PLACENTA, UMBILICAL CORD AND FETAL MEMBRANES, BIRTH:
- PLACENTA SMALL FOR GESTATIONAL AGE (160 GRAMS -- TRIMMED, POST-FIXATION WEIGHT).
- THREE VESSEL UMBILICAL CORD WITHIN NORMAL LIMITS.
- FETAL MEMBRANES WITHIN NORMAL LIMITS.
- PLACENTAL DISC WITH THIRD TRIMESTER VILLI WITH:
-- OLD CENTRAL TRANSMURAL INFARCT (1.7 CM MAXIMAL DIMENSION).

COMMENT:
The 10th percentile placental mass (pre-fixation) for 34 weeks and 2 days is approximately 390 grams.

Overview of placental pathology

Approach

The pathology of the placenta is diverse and is not easy to group.

It terms of remembering things. It is probably easiest to take a combined anatomical, etiologic and morphologic approach.

Anatomical basis:

• Cord.
• Membranes.
• Disc.

Etiologic:

• Congential.
• Infectious.
• Neoplastic.
• Endocrine.
• Trauma.
• Vascular.
• Degenerative.
• Autoimmune.
• Toxic.
• Idiopathic.

Compartmental:

• Vasculature.
• Membranes.
• Parenchyma:
  • Maternal part (decidua).
  • Fetal part (villi, cord).

Common entities/diagnoses

• Normal.
• Chorioamnionitis.
• Placental abruption.
• Meconium.
• Hypertensive changes.

Sign out

What should be commented on...

• Placenta:
  • Maturity of villi (2nd or 3rd trimester).
  • Infarction?
    • Subchorionic less important than maternal aspect.
    • Peripheral aspect of placental disc less important than central region of disc.
  • Blood vessels.
    • Maternal.
    • Fetal.
• Membranes.
  • Membranitis?
  • Chorioamnionitis?
• Cord:
  • 3 vessel?
  • Vasculitis/inflammation?

Mnemonic: chorio, cord, vessels, villi (maturity, infarction).

Normal placenta

PLACENTA, UMBILICAL CORD AND FETAL MEMBRANES, BIRTH:
- THREE VESSEL UMBILICAL CORD WITHIN NORMAL LIMITS.
- FETAL MEMBRANES WITHIN NORMAL LIMITS.
- PLACENTAL DISC WITH THIRD TRIMESTER VILLI WITHIN NORMAL LIMITS.

C-section

PLACENTA, UMBILICAL CORD AND FETAL MEMBRANES, CAESAREAN SECTION:
- THREE VESSEL UMBILICAL CORD WITHIN NORMAL LIMITS.
- FETAL MEMBRANES WITHIN NORMAL LIMITS.
- PLACENTAL DISC WITH THIRD TRIMESTER VILLI WITHIN NORMAL LIMITS.

Cord pathology

• Two vessel cord.
• Hypercoiling/Hypocoiling.
• Abnormal insertion.
• Cord knots (true vs. false).
• Strictures.
• Hematoma.
• Hemangioma.
• Benign cyst.

Two vessel umbilical cord

• AKA two vessel cord.
• AKA single umbilical artery.

Main article: Two vessel umbilical cord

Insertion

Marginal insertion

Definition:

• The umbilical cord is attached to the placental disc at its margin.

Prevalence:

• Approximately 12% of placentas.

Relevance:

• None according to WMSP.
  • In theory, the cord, dependent on its relation to the internal os, is at greater risk of injury (leading to vasa previa) and compression (fetal hypoxia). A retrospective study found cord position in relation to the internal os is predictive for vasa previa.

Velamentous insertion

Definition:

• The umbilical cord inserts into the fetal membranes.
  • The vessels are not protected by Wharton's jelly.
    • Wharton's jelly = the connective tissue surrounding the vessels in the cord.

Details:

• 3/4 of the time the vessel also branch; in the remaining 1/4 the vessels stay together.

Relevance:

• Increased risk of vasa previa.

Sign out

PLACENTA, UMBILICAL CORDS AND FETAL MEMBRANES, BIRTH:
- THREE VESSEL UMBILICAL CORD WITH A VELAMENTOUS INSERTION, OTHERWISE WITHIN NORMAL LIMITS.
- FETAL MEMBRANES WITHIN NORMAL LIMITS.
- PLACENTAL DISC WITH THIRD TRIMESTER VILLI WITHIN NORMAL LIMITS.

Umbilical knot

• AKA umbilical cord knot.
• AKA cord knot.
• AKA true knot.

General

• Prevalence ~1.25%.
• Increase risk of stillbirth; odds ratio 3.93.

Gross

Work-up:

• Diameter measures and colour on both sides of the knot.
• Knot should be untied to assess for deformation of Wharton's jelly.
• Sections from both sides of the knot - to look for thrombi.

Note:

• False knots (large diameter - focally) are common - they cannot be untied.

Microscopic

Features:

• +/-Thrombi.
  • Fibrin deposition.
• +/-Lines of Zahn.

Images:

• Lines of Zahn (utah.edu).
• Lines of Zahn (ucsf.edu).

Coiling

• Hypo- and hypercoiling are both considered problematic.
  • Normal: 1-3 coils/10 cm.
• Associated with cord stricture, which is usu. at the fetal end of the cord.

Notes:

• There is little uniformity in how coiling is assessed in the medical literature - though 10% and 90% are considered the cut-points for normal.
  • What are the 10% and 90% cut-points? They are not given in WMSP. UT access to a journal article that might have it is screwed-up.

Cord hematoma

Features:

• Rare ~ 1/5500.
• Mortality ~50% is severe.

Membranes

• Squamous metaplasia.
• Chorioamnionitis - see infection section.

Amnion nodosum

Main article: Amnion nodosum

Placental meconium

Main article: Placental meconium

Squamous metaplasia of the amnion

General

• Benign common finding thought to be of no clinical significance.
  • One case report suggesting an association with chorioamnionitis.
• Needs to be separated from amnion nodosum - important.

Gross

Features:

• White (or yellow) plaques - irregular outline.

DDx:

• Amnion nodosum - small (~1-5 mm), round, classically yellow.

Images:

• Amnion nodosum & squamous metaplasia of the amnion (archivesofpathology.org).

Microscopic

Features:

• Dense, paucicellular (pink) compact keratin - key feature.

Image:

• Squmous metaplasia of the amnion (flylib.com).

Circumvallate placenta

• AKA circumvallate insertion of the membranes.

General

• May be associated with placental abruption.

Note:

• Membranes usually attach to the edge of the placenta.

Gross

• Fetal membranes attach to the fetal surface of the placenta away from the margin of the placental disc.

Classification:

• Partial - not circumferential.
• Complete.

DDx:

• Circummarginate placenta.

Images:

• Circumvallate placenta - partial and complete (utah.edu).
• Circumvallate placenta (utah.edu).

Twin placentas

Main article: Twin placentas

These are often submitted... even if they are normal. In these specimens, usually, the chorion is the key.

It covers:

• Monozygotic vs. dizygotic twins.
• Twin-to-twin transfusion syndrome.

Placental disc

Villous edema

General

• Non-specific finding.
• Reported in associated with congenital adrenal hyperplasia for the stem villi.

Microscopic

Features:

• "Swiss chesse-like" appearance / bubbly appearance.
• Usually patchy and focal.

Note:

• Cistern formation is reported in the stem villi in association with congenital adrenal hyperplasia.

DDx:

• Chorioamnionitis.
• Fetal edema.
• Idiopathic (no cause apparent).
• Placental villous immaturity.

Image:

• villous edema (yale.edu).

Placental villous immaturity

Main article: Placental villous immaturity

Villous hypoplasia

• AKA terminal villus deficiency.

Main article: Villous hypoplasia

Diseases of the placental attachment

Placenta creta

Includes placenta accreta, placenta increta, and placenta percreta.

Main article: Placenta creta

Placental abruption

Main article: Placental abruption

Inflammatory pathologies

Overview of infections

General:

• Infection usually ascending, i.e. from vagina up through cervix.
  • Associated with intercourse.
• Hematogenous rare - manifest as villitis.
  • Think TORCH infections (toxoplasmosis, others (syphilis, TB, listeriosis), rubella, cytomegalovirus, herpes simplex virus).
• Funisitis usually follows chorioamnionitis.
  • Inflammatory cells in umbilical cord are fetal (trivia).

Types

By site:

• Fetal membranes: chorioamnionitis, membranitis.
• Umbilical cord: funisitis.
• Placenta: placentitis, villitis.

Membranitis

Chorionitis redirects here.

General

• Early chorioamnionitis.
• Controversial.^{[citation needed]}

Microscopic

Features:

• PMNs in the decidua.
• +/-PMNs in subamniotic tissue.
• +/-Necrosis in decidua or chorion/subamniotic tissue.

Note:

• Plasma cells in the decidua = chronic deciduitis.

DDx:

• Chorioamnionitis.

Grading membranitis

Sternberg:

1. PMNs - decidua only.
2. PMNs - in subamniotic tissue.
3. 1 or 2 + necrosis in decidua or chorion/subamniotic tissue.

Sign out

PLACENTA, UMBILICAL CORD AND FETAL MEMBRANES, CESAERIAN SECTION:
- FETAL MEMBRANES WITH CHORIONITIS.
- THREE VESSEL UMBILICAL CORD WITH VASCULITIS.
- PLACENTAL DISC WITH THIRD TRIMESTER VILLI.

Waffle

PLACENTA, UMBILICAL CORD AND FETAL MEMBRANES, BIRTH:
- FETAL MEMBRANES WITH MECONIUM-LADEN MACROPHAGES AND ABUNDANT DECIDUAL NEUTROPHILS
  SUSPICIOUS FOR EARLY CHORIONITIS.
- PLACENTAL DISC WITH THIRD TRIMESTER VILLI.
- THREE VESSEL UMBILICAL CORD WITHIN NORMAL LIMITS.

Chorioamnionitis

Main article: Chorioamnionitis

Umbilical cord vasculitis

Main article: Umbilical cord vasculitis

Funisitis

Main article: Funisitis

• Inflammation of Wharton's jelly - the connective tissue of the umbilical cord.

Acute villitis

Main article: Acute villitis

Villitis of unknown etiology

Main article: Villitis of unknown etiology

Chronic intervillitis

• AKA chronic intervillositis.

General

• Rare.
• Massive chronic intervillitis - associated IUGR, spontaneous abortion, perinatal fetal death.
• Recurs.

Microscopic

Features:

• Intervillous inflammatory cells:
  • Lymphocytes.
  • Histiocytes.
• Fibrinoid deposition.

Images

• 

  Intervillitis - intermed. mag. (WC)

• 

  Intervillitis - very high mag. (WC)

Chronic deciduitis

• AKA plasma cell deciduitis.

Main article: Chronic deciduitis

Placental infarction

True infarcts

Main article: Placental infarct

Perivillous fibrin deposition

• Abbreviation PFD.

General

• Thought to be an immunologic problem - resulting in platelet activation and fibrin deposition.
• May be associated with diabetes mellitus.

Gross

• Pale (white).
• Firm.
• White fibrous sepatae.

Microscopic

Features:

• Acellular eosinophilic material around formed villi.
• Obliteration of intervillous space.
  • Intervillous distance increased vis-a-vis normal - key feature.

Notes:

• Nuclei of villi are usually preserved.
• Villi may have secondary infarction, i.e. there may be nuclear destruction (karyolysis, karyorrhexis, pyknosis).

DDx:

• Placental infarction - loss of nuclei in the villi (below the edge of the lesion).
• Massive perivillous fibrin deposition (maternal floor infarct).

Images:

• APLA syndrome (upmc.edu).

Sign out

Thrombi

PLACENTA, UMBILICAL CORD AND FETAL MEMBRANES, BIRTH:
- THREE VESSEL UMBILICAL CORD WITHIN NORMAL LIMITS.
- FETAL MEMBRANES WITHIN NORMAL LIMITS.
- PLACENTAL DISC WITH THIRD TRIMESTER VILLI AND THREE LARGE INTERVILLOUS 
THROMBI (BLOCKS A7-A9).

Maternal floor infarction

• Abbreviated MFI.
• Formally placental maternal floor infarction.
• AKA massive perivillous fibrin deposition.

Main article: Maternal floor infarction

Fetal disease

Fetal thrombotic vasculopathy

• Abbreviated FTV.
• A large number of terms are used for this including:
  • Fibrinous vasculosis.
  • Fibromuscular sclerosis.
  • Fetal artery stem thrombosis.
• The multitude of terms reflects the confusion about this finding and that it has numerous etiologies.

Main article: Fetal thrombotic vasculopathy

Hemorrhagic endovasculitis

• Abbreviated HEV.

General

• Associated with stillbirth.

Microscopic

Features:

• Walls of the (fetal) placental blood vessels (in the villi) are disrupted.
• +/-Intraluminal necrotic debris.
• RBC fragmentation.

Maternal disease

Hypertensive changes

General

Associated pathologic changes:

• Placental infarcts.
• Increased syncytial knots.
• Hypovascularity of the villi.
• Cytotrophoblastic proliferation.
• Thickening of the trophoblastic basement membrane.

Microscopic

Features:

• Enlarged endothelial cells - fetal capillaries.
• Atherosis of the spiral arteries - placental bed (maternal).

Notes:

• One should look for the changes in the membrane roll, not the maternal surface.

Images:

• Pregnancy-induced hypertension (pathxchange.org).

Hypertrophic decidual vasculopathy

AKA decidual vasculopathy.

Main article: Hypertrophic decidual vasculopathy

HELLP syndrome

Main article: HELLP syndrome

Malaria

Main article: Malaria

General

• Uncommon in Canada.
• May lead to fetal demise.

Microscopic

Feature:

• RBCs with basophilic dots ~1-2 micrometres.

Image

• 

  Maternal malaria - very high mag. (WC)

Tumours

Main article: Gestational trophoblastic disease

Chorangioma

Main article: Chorangioma

Chorangiomatosis

General

Associated with:

• Preeclampsia.
• IUGR.

Gross

• Multiple tan nodules.

Microscopic

Features:

• Multiple chorangiomas - the difference between chorangioma and chorangiomatosis is not well defined.

Images:

• Chorangiomatosis - several images (upmc.edu).

Chorangiosis

Main article: Chorangiosis

Other

Fetus papyraceus

• May be spelled foetus papyraceus.
• AKA fetus compressus.

Main article: Fetus papyraceus

Placental mesenchymal dysplasia

• Abbreviated PMD.

Main article: Placental mesenchymal dysplasia

Placental cysts and pseudocysts

Types:

• Amnionic epithelial inclusion cyst (amniotic cyst).
• Epidermal inclusion cyst - lined by keratinized squamous epithelium.
• Chorionic cyst (AKA chorionic pseudocyts).
• Cell island cyst.

Other considerations:

• Hematoma.
• Fibrin-lined pseudocyst.

General:

• Usually good outcome.
• Large cysts (>4.5 cm) or multiple cysts (>3) are associated with IUGR.

Images:

• Subchorionic cysts (jultrasoundmed.org).

See also

• Chorionic villi.
• Endometrium.
• Pregnancy.
• Gestational trophoblastic disease.
• TORCH infections.

Recommended reading

• Langston C, Kaplan C, Macpherson T, et al. (May 1997). "Practice guideline for examination of the placenta: developed by the Placental Pathology Practice Guideline Development Task Force of the College of American Pathologists". Arch. Pathol. Lab. Med. 121 (5): 449–76. PMID 9167599.
• Baergen, Rebecca N. (2005). Manual of Benirschke and Kaufmann's Pathology of the Human Placenta (1st ed.). Springer. ISBN 978-0387220895.

External links

• Cord complications (emedicine.medscape.com).
• Placenta notes (palpath.com).