Placenta

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

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 = Caesarian 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.

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.

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 I generated 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 almost certainly more reproducible than arbitrary descriptors which require experience and a continuing case volume to calibrate.

Placentomegaly

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.

Associations:

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

Sign out

PLACENTA, UMBILICAL CORD AND FETAL MEMBRANES, CESAERIAN SECTION:
- 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, CAESARIAN 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.

Associations

• Associated with congenital abnormalities, esp. cardiac - key point.
  • Thought to be an acquired defect (as prevalence is lower early in gestation).
• May be seen in association of other cord abnormalities (e.g. marginal insertion, velamentous insertion).
• In apparently well (liveborn) infants it is associated with (occult) renal abnormalities, specifically vesico-ureteric reflux; there is no evidence for other abnormalities.
• Associated with maternal diabetes.

Image:

• SUA (glown.com).

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.

Knots

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.

Image: Hematoma (flylib.com).

Membranes

• Squamous metaplasia.
• Chorioamnionitis - see infection section.

Amnion nodosum

General

• Associated with (long-standing) oligohydramnios.
• Should be separated from squamous metaplasia of amnion.

Gross

Features:

• Yellow nodules ~ 1-5 mm.
  • Some think they are white.

DDx:

• Squamous metaplasia of the amnion - large irregular patches, usu. white.

Images:

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

Microscopic

Features:

• Stratified squamous epithelium - non-keratinizing or minimal keratin.
• Amorphous acidophilic (pink) debris.

Note:

• Normal amnion = simple epithelium.

Images:

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

Placental meconium

• AKA meconium staining.

General

• Associated with fetal distress.
• Small amount - at term - is considered to be normal.

Other meconium-related pathology:

• Meconium peritonitis.
• Meconium ileus.

Gross

• Green/green discolourization.

Microscopic

Features:

• Meconium histiocytes - key feature.
  • Macrophages with brown fine granular pigment.
• Pseudostratified epithelium (amnion) - low power.
• Amnion - columnar morphology (normally cuboidal).
• "Drop-out" of individual amnion cells / loss of individual cells.

Time of meconium passage:

• <1 h - no staining of membranes.
• 1-3 h - amnion is stained.
• >3 h - chorion is stained.

DDx:

• Hemosiderin-laden macrophages.
  • This is sorted-out with an iron stain -- see below.

Notes:

• The above time course is disputed - in vitro experiments suggest it is considerably longer.

Images:

• Meconium-laden macrophages - high mag. (WC).
• Meconium-laden macrophages - intermed. mag. (WC).

Special stains

• Hemosiderin +ve in hemosiderin-laden macrophages.
• PAS +ve in meconium-laden macrophages.

Useful to differentiate hemosiderin-laden macrophages and meconium laden macrophages:

• Hemosiderin stain -- +ve for old blood.
  • Prussian-blue stain = hemosiderin stain.

Notes:

• PAS-D -- +ve in meconium... though may rarely stain hemosiderin.
• Meconium contains bile.

Sign out

PLACENTA, UMBILICAL CORD AND FETAL MEMBRANES, BIRTH:
- FETAL MEMBRANES WITH MECONIUM-LADEN MACROPHAGES, NEGATIVE FOR CHORIOAMNIONITIS.
- THREE VESSEL UMBILICAL CORD WITHIN NORMAL LIMITS.
- PLACENTAL DISC WITH THIRD TRIMESTER VILLI WITHIN NORMAL LIMITS.

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.

Microscopic

Features:

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

DDx:

• Chorioamnionitis.
• Fetal edema.
• Idiopathic (no cause apparent).

Image:

• villous edema (yale.edu).

Placental villous immaturity

• AKA distal villous immaturity, AKA villous immaturity, AKA villous dysmaturity.

General

Associated with:

• Diabetes mellitus.
• Beckwith-Wiedemann syndrome.
• Intrauterine fetal demise near term.

Microscopic

Features:

• Large villi with:
  • Increased number of capillaries.
  • Edema.
  • Macrophages.
  • Large diffusion distance (vessel-to-villous surface distance large).

DDx:

• Chorangiosis.

Images:

• WC:
  • Placental villous immaturity - low mag. (WC).
  • Placental villous immaturity - intermed. mag. (WC).

Diseases of the placental attachment

Placenta creta

• What?
  • Trophoblastic tissue deeper than it should be.
• Clinical?
  • Postpartum hemorrhage leading to a hysterectomy.
• Pathogenesis?
  • It is suspected that it arises as there is defect in the endometrium/myometrium -- not deep trophoblastic invasion.

Note:

• Normal: trophoblastic tissue attaches to the decidua.

Placenta accreta

• Trophoblastic tissue (directly) adherent to the myometrium.

Image:

• Placenta accreta (med.utah.edu).

Placenta increta

• Trophoblastic tissue entends into the myometrium.

Placenta increta

• Trophoblastic tissue penetrates through the myometrium.

Placental abruption

General

Classic clinical manifestations:

• Vaginal bleeding (~70%).
• Abdominal pain (~50%).
• Fetal heart rate abnormalities (~70%).

Sign-out:

• Pathologists should sign-out this as "focal adherent retroplacental hematoma".
  • The pathologic findings may be due to abruption or manual removal of the placenta.

Gross

Features:

• Large adherent blood clot.
• Disc depression on maternal side.

Notes:

• Loosely attached clot less convincing.
• Central haemorrhage is the most worrisome.

Microscopic

Features:

1. Decidual hemorrhage.
   • Blood in the decidua.
2. Intravillous hemorrhage, AKA villous stromal hemorrhage.
   • "Bags of blood" - blood outside of vessels in the villi.
     • Should not be confused with congested villi.

Notes:

• There are no definitive microscopic findings for placental abruption.
• Intravillous hemorrhage is non-specific - may arise in the following: early placental infarct, cord compression, abdominal trauma.

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

General

• Controversial. (???)

Microscopic

Features:

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

Grading membranitis

Sternberg:

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

Chorioamnionitis

General

• Associated with pre-term labour.
  • Classically described as due to an ascending infection.
• At term usually non-infectious.

Clinical features:

• Maternal fever.
• Premature rupture of membranes (PROM).
• Non-reassuring fetal heart rate (NRFHR).

Microscopic

Features:

• Neutrophils in the amnion.
  • Amnion:
    • The simple cuboidal epithelium and the paucicellular underlying connective tissue
    • Separated from the chorion by an artefactual cleft.

Note:

• Severe cases may have umbilical cord vasculitis or funisitis.

Images:

• WC:
  • Chorioamnionitis - low mag. (WC).
  • Chorioamnionitis - high mag. (WC).
  • Chorioamnionitis - very high mag. (WC).

Grading chorioamnionitis

Chorioamnionitis:

1. placental chorionic plate only.
2. 1 + subamniotic tissue.
3. 1 or 2 + necrosis or abscess.

Sign out

PLACENTA, UMBILICAL CORD AND FETAL MEMBRANES, CESAERIAN SECTION:
- CHORIOAMNIONITIS.
- FETAL MEMBRANES NEGATIVE MECONIUM.
- THREE VESSEL UMBILICAL CORD WITHIN NORMAL LIMITS.
- PLACENTAL DISC WITH THIRD TRIMESTER VILLI.
- THROMBUS OF THE PLACENTAL DISC (1.3 CM - MAXIMAL DIMENSION).

Umbilical cord vasculitis

General

• Usually seen together with chorioamnionitis.
  • May be described as the fetal response to chorioamnionitis.
• Presence considered to be a good prognosticator.

Microscopic

Features:

• Neutrophils in the vessels of the umbilical cord.
• Wharton's jelly without neutrophils.

Note:

• Umbilical vein involvement (umbilical phlebitis) precedes umbilical artery involvement (umbilical arteritis).

DDx:

• Funisitis - neutrophils also in the connective tissue of the umbilical cord (Wharton's jelly).

Grading

Umbilical cord vasculitis:

• +0.5 for each vessel.
• +0.5 for each vessel with severe involvement.

Funisitis

General

• Usu. seen together with chorioamnionitis.

Microscopic

Features:

• Neutrophils in the vessels of the umbilical cord and Wharton's jelly.

Note:

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

Grading funisitis

Funisitis:

1. Focal inflammation.
2. Diffuse inflammation.
3. Necrosis - in umbilical vessels or Wharton jelly.

Sign out

PLACENTA, UMBILICAL CORD AND FETAL MEMBRANES, BIRTH:
- CHORIOAMNIONITIS.
- THREE VESSEL UMBILICAL CORD WITH FUNISITIS.
- PLACENTAL DISC WITH THIRD TRIMESTER VILLI.
- TWO THROMBI OF THE PLACENTAL DISC (LARGEST 0.9 CM - MAXIMAL DIMENSION).

Villitis of unknown etiology

• Abbreviated VUE.

General

Features:

• Usually term placenta.
• Prevalence: 5% to 15% of all placentas.
• Associated with:
  • Intrauterine growth restriction (IUGR).
  • Recurrent reproductive loss/adverse outcomes in subsequent pregnancies -- key point.
    • Recurrence in up 37% of cases.

Etiology:

• Unknown - as the name of the entity suggests.
  • Suspected to be immune-mediated.

Microscopic

Features:

• Lymphocytes in villous stroma - key feature.
  • Usually focal/patchy.
  • Lymphocytes: maternal derivation, T-lymphocytes -- mostly CD8-positive.
• +/-Intervillositis (lymphocytes between villi).
• +/-Histiocytes.

Notes:

• Lymphocytes are smaller and stain darker than the cells of the villi. (???)
• Neutrophils are usually absent. A significant number of 'em is suggestive of an infectious villitis.
• Infective villitis is usu. B-cell predominant.
• No plasma cells - this suggests an infectious etiology.
  • Plasma cells may be seen in the decidua -- these can be ignored.

Images:

• WC:
  • VUE - intermed. mag. (WC).
  • VUE - very high mag. (WC).
• www:
  • VUE (bmj.com).
  • VUE (flickr.com).
  • VUE (flickr.com).

Intervillitis

• AKA 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.

General

• Associated with preterm labour.

Microscopic

Features:

• Plasma cells within the decidua.

Notes:

• Decidua = maternal tissue.

Images:

• Chronic deciduitis - intermed. mag. (WC).
• Chronic deciduitis - very high mag. (WC).

Placental infarction

True infarcts

Main article: Infarction

General

• May be seen in conjunction with a retroplacental hematoma.
• Infarcts frequently associated with hypertension.

Note: "Maternal floor infarct" is not a true infarct.

Gross

Features:

• Early - red.
• Late - white/grey.

Significant infarcts

• > 3cm --or-- central location --or-- in 1st or 2nd trimester.^{[citation needed]}
  • Small foci are accepted in term placentae - typically at periphery.

Images:

• Placental infarcts (pathweb.uchc.edu).
• Placental infarcts (med.utah.edu).

Microscopic

Features:

1. Necrosis of villi; hyaline material (acellular eosinophilic material) replaces the stroma of the villi.
2. Loss of intervillous space.
   • Villi appear to be crowded.
     • Normal spacing is ~1x smallest villus or larger.
       • In perivillous fibrin deposition - spacing usu. larger than normal.
3. Prominent syncytial knots.
4. Thickened trophoblastic basement membrane (below cytotrophoblasts).
5. +/-Changes seen in decidual vasculopathy:
   • Acute atherosis (vaguely like atherosclerosis).
     • Fibrinoid necrosis.
     • Vessel wall lipid deposition.

Images:

• WC:
  • Placental infarct - low mag. (WC).
  • Placental infarct - intermed. mag. (WC).
• www:
  • Recent infarct (pathweb.uchc.edu).
  • Placental infarct (umpmc.edu).
  • Placental infarct - necrotic villi (mda-sy.com).

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).

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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.

General

• Not a true infact.
  • It is really fibrin deposition.

Associations:

• Intrauterine growth restriction (IUGR).
• Anti-phospholipid antibody (APLA) syndrome.
  • APLA is associated with recurrent miscarriage - can be treated with heparin + ASA.
• Pregnancy-induced hypertension.

Gross

Features:

• +/-Thickened placenta.
• Maternal aspect of placental disc irregular or lobulated appearance.
• +/-Yellowish discolourization.

Microscopic

Features:

• Extensive fibrin deposition around villi on maternal aspect - see: Perivillous fibrin deposition.
  • Described as having a "net-like" pattern.
  • "Extensive" - either of the following:
    1. Micro: one slide with >50% of villi involved.
       • Gross: full thickness involvement.
    2. Micro: maternal floor has at least 3 mm of fibrin on one slide.
       • Gross: maternal floor diffusely involved.

DDx:

• Perivillous fibrin deposition - less perivillous fibrin.
• Placental infarction.

Images:

• Maternal floor infarct (flickr.com).
• Maternal floor infarct (flickr.com).
• Maternal floor infarct - several images (upmc.edu).

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PLACENTA, UMBILICAL CORD AND FETAL MEMBRANES, BIRTH:
- THREE VESSEL UMBILICAL CORD WITHIN NORMAL LIMITS.
- FETAL MEMBRANES WITHIN NORMAL LIMITS.
- SMALL PLACENTAL DISC WITH MASSIVE PERIVILLOUS FIBRIN DEPOSITION, SEE COMMENT.

COMMENT:
Massive perivillous fibrin deposition (MPVFD) is associated with intrauterine 
growth restriction (IUGR). MPVFD is described in association with in 
anti-phospholipid antibody (APLA) syndrome, pregnancy-induced hypertension and 
congenital infections. Perivillous fibrin deposition may be seen in diabetes.

There is no apparent infection. Changes suggestive of decidual vasculopathy 
are not apparent. Changes suggestive of fetal thrombotic vasculopathy are 
not identified.

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.

General

• May cause IUGR.
• Associated with cerebral palsy and common in perinatal deaths.

Microscopic

Features:

• Thrombus in the fetal vasculature +/- recanalization.
  • Eosinophilic (light pink on H&E), moderately granular intravascular material (fibrin) with layering.
• Clustered fibrotic villi without blood vessels - key feature.
  • This is a chronic change.

Images:

• www:
  • FTV (bmj.com).
  • Thrombus - rat (bmj.com).
  • FTV - low mag. (womenandinfants.org).
  • FTV - high mag. (womenandinfants.org).
• WC:
  • FTV - intermed. mag. (WC).
  • FTV - high mag. (WC).

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.

Hypertrophic decidual vasculopathy

General

• A change seen in hypertension.
• Seen in intrauterine growth restriction (IUGR).

Microscopic

Features:

• Mild or moderate:
  1. Perivascular inflammatory cells.
  2. +/-Vascular thrombosis.
  3. Smooth muscle hypertrophy.
  4. Endothelial hyperplasia.
     • Above two lead to narrowing of the decidual spiral arteries -- key feature.
• Severe:
  1. Atherosis of maternal blood vessels.
     • Foamy macrophages within vascular wall.
  2. Fibrinoid necrosis of vessel wall (amorphous eosinophilic material vessel wall).

Note:

• Smooth muscle hypertrophy can also be understood as lack of physiological conversion of spiral arteries of the uterus.

Images:

• WC:
  • HDV - intermed. mag. (WC).
  • HDV - low mag. (WC).
• www:
  • Atherosis (upmc.edu).

HELLP syndrome

General

• Diagnosed clinically.
• Pathologically not the same as severe preclampsia.

Definition:

• H = hemolysis.
• EL = elevated liver enzymes.
• LP = low platelets.

Microscopic

Features:

• Thrombotic microangiopathic vasculopathy.
  • In essence: severe hypertrophic decidual vasculopathy. (???)

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

General

• Hamartoma-like growth in the placenta consisting of blood vessels.

Epidemiology:

• Often benign/insignificant; large lesions (>4 cm or >5 cm) or multiple lesions are significant.
• May be association with:
  • Fetal maternal haemorrhage.
  • Fetal hydrops.
  • IUGR.
• Incidence: ~1 in 100 placentas.

Gross

• White lesions.
  • Occasionally red lesions.

Microscopic

Features:

• Mass of capillaries - key feature.
• +/-High cellularity.
• +/-Degenerative changes.

Images:

• Chorangioma - intermed. mag. (WC).
• Chorangioma - low mag. (WC).

Notes:

• Must be differentiated from chorangiomatosis (associated with preeclampsia & IUGR) and chorangiosis (assoc. with maternal diabetes mellitus).

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

General

• Should not be confused with chorangioma.
• Relative common among babies in ICU ~5%.

Associations:

• Maternal hypoxia:
  • Smoking.
  • Altitude.
  • Gestational diabetes.

Gross

• Usually not seen on gross pathology.

Microscopic

Features:

• Increased blood vessels in the terminal villi.
  • Altshuler criteria: "a minimum of 10 villi, each with 10 or more vascular channels, in 3 or more random, non-infarcted placental areas when using a ×10 ocular."
    • The definition suffers from IPFitis.
• Lesion not well circumscribed.
• Villi tend to be larger and have centrally placed blood vessels.

Notes:

• Normal villi have up to five vascular channels.

Images:

• Chorangiosis - intermed. mag. (WC).
• Chorangiosis - high mag. (WC).

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PLACENTA, UMBILICAL CORD AND FETAL MEMBRANES, CESAERIAN SECTION:
- THREE VESSEL UMBILICAL CORD WITHIN NORMAL LIMITS.
- FETAL MEMBRANES WITHIN MECONIUM STAINING OF THE AMNION, NEGATIVE FOR CHORIOAMNIONITIS.
- PLACENTAL DISC WITH:
-- CHORANGIOSIS.
-- FOCAL PERIVILLOUS FIBRIN DEPOSITION.

COMMENT:
Chorangiosis is a non-specific finding that may be associated with diabetes, smoking or high altitude.

Other

Fetus papyraceus

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

General

• Remnant of a dead fetus usu. from a twin pregnancy.
  • No clinical consequence for mother and remaining fetus.

Clinical:

• Documented multiple gestation by imaging.
• Elevated AFP.
• May be a "fetal reduction" in the context of in vitro fertilization (IVF).

Note:

• "Papyraceus" = paper-like.

Gross

• Pale yellow flattened disk or plaque with a pigmented macule - on membranes or placental disc.

Microscopic

Features:

• Fetal structures - such as:
  • Cartilage.
  • Bone.

Images:

• Fetus papyraceus (nejm.org).
• Fetus papyraceus (upmc.edu).
• Fetus papyraceus (neonet.ch).

Placental mesenchymal dysplasia

General

• Very rare ~ 70 reported cases.
• Etiology unknown.

Associations:

• IUGR ~ 50% of cases.
• Fetal demise ~ 40-45% of cases.
• Beckwith-Wiedemann syndrome.

Gross

Features:

• Placentomegaly.
• Grape-like vesicles.

DDx - gross:

• Partial hydatidiform mole.

Image:

• PMD (nih.gov).

Microscopic

Features:

• Stem villi with edema (hydropic changes) and few blood vessels.
• Paucivascular (few blood vessels) or avascular villi.

Note:

• Stem villi = large villi with a fibrotic core and (fetal) arteries and veins.

Image:

• PMD (nih.gov).

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).