Placenta

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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 a pathologist:

  • Abnormalities in the:
    1. Fetus:
      • Bad fetal outcome.
      • Suspected or known congenital abnormalities or chromosomal abnormalities.
    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.

Bleeding in late pregnancy

DDx of bleeding in late pregnancy:

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

Clinical screening tests

  • PAPP-A - low values seen in aneuploidy.[1]
Main article: Pregnancy

Normal histology

Amnion

General:

  • Next to fetus, surrounds amniotic fluid, avascular.

Characteristics:

  • Characterized by a single layer of cells.[2]
    • Cuboidal/squamoid shape.
    • Eosinophilic cytoplasm.
    • Central nucleus.
  • Squamous metaplasia may be seen at cord insertion.
  • Basement membrane.
  • 'Compact layer'.[2]
  • 'Fibroblastic layer'.[2]

Chorion

General:

  • Surrounds amnion.

Characteristics:

  • Layers:[3]
    • 'Reticular layer' - cellular (inner aspect).
    • 'Pseudo-basemement membrane'.
    • 'Outer trophoblastic layer'.
  • Has blood vessels.
  • Opposed to "trophoblastic X cells" on side opposite of amnion.[2]
    • Beneath of the "trophoblastic X cells" is decidua (mnemonic NEW = nucleus central, eosinophilic, well-defined cell border), which is maternal tissue.

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.
  • Mass (weight) -- should be done 'trimmed' (cord cut-off, membrane cut-off).
  • Umbilical cord
    • Attachment.
      • Location: central, eccentric, marginal.
        • Marginal attachment assoc. with hypertension[4]
      • Membranous or velamentous (veil-like) insertion.
        • Vessels separate/branch prior to reaching placental disc.
      • Furcate insertion - vessel run on fetal surface (more exposed to trauma).
    • Knots (false vs. true).
      • False knots are nothing to worry about -- look like a knot but aren't really one.
    • Twisting/coiling.
    • Number of vessels.
      • Normal: 2 arteries, 1 vein.
  • Membranes - shiny, thin, translucent
    • Attachment: marginal (normal), circummarginate (inside edge), circumvallated (folding on self).
  • Placental disc.
    • Fetal surface - normal is shinny (dull in chorioamnionitis).
    • Maternal surface - are the cotyledons intact?

Sections

  • Cord two sections.
  • Cord at insertion.
  • Membranes (rolled).
  • Placenta - full thickness (maternal and fetal surface).

Placental membranes

Appearance:[5]

  • Normal - shiny.
  • Choriomnionitis - opaque/dull.
  • Meconium - green.
  • Amnion nodosum.
    • AKA squamous metaplasia of amnion.[6]
    • Assoc. with oligohydramnios.[7]
    • Gross: - (single) yellow patch or yellow nodules .

Placental mass

Placental mass by gestational age:[8]

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[9] 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).

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.

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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).

Cord pathology

  • Two vessel cord.
  • Hypercoiling.
  • Abnormal insertion.
  • Cord knots (true vs. false).
  • Strictures.
  • Hematoma.

Two vessel cord

  • AKA single umbilical artery.
  • Associated with congenital abnormalities, esp. cardiac - key point.[10]
    • Thought to be an acquired defect (as prevalence is lower in early in gestation).
  • May be seen in association of other cord abnormalities (e.g. marginal insertion, velamentous insertion).

Image:

Insertion

Marginal insertion

Definition:

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

Prevalence:

  • Approximately 12% of placentas.[10]

Relevance:

  • None according to WMSP.[10]
    • 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.[12]

Velamentous insertion

Definition:

  • The umbilical cord inserts into the fetal membranes.[10]
    • The vessels are not protected by Wharton's jelly.
      • Wharton's jelly = the connective tissue surrounding the vessels in the cord.

Details:[10]

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

Relevance:

  • Increased risk of vasa previa.[12]

Knots

General

  • Prevalence ~1.25%.[13][14]
  • Increase risk of stillbirth; odds ratio 3.93.[13]

Gross

Work-up:[14]

  • 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:

Coiling

General

  • There is little uniformity in how coiling is assessed in the medical literature - though 10% and 90% are considered the cut-points for normal.[15]
  • Hypo- and hypercoiling are both considered problematic.[10]
  • What are the 10% and 90% cut-points? They are not given in WMSP. UT access to a journal article[16] that might have it is screwed-up.

Twin placentas

These are often submitted... even if they are normal.

General

No membrane between fetuses.

  • Split at approx. 7th day.

Diamnionic-monochorionic (DiMo)

  • No interposed chorion.[17]
  • Always monozygotic.
  • Highest risk of TTTS (twin-to-twin transfusion syndrome).

Diamnionic-dichorionic (DiDi)

  • Most dizygotic (70%), may be monozygotic (30%).
  • If monozygotic -- split before 3 days.

Twin-to-twin transfusion syndrome

General

  • Abbreviated as TTTS.

Definition:

  • Monozygotic twins that share a placental disc, have vessels which cross-over between the twins that lead to a blood imbalance between the two twins.
    • Only seen in monozygotic twins.
    • Vascular connection may be vein-to-vein, artery-to-vein, artery-to-artery (uncommon).[18]

Prevalence:

  • Seen in ~15% of monozygotic twins.[18]

Clinical:

  • Donor:
    • Twin: hypovolemic, oliguric, oligohydramnic, +/- anemia, +/-hypoglycemia, +/- small pale organs.
    • Placental disc: large, pale.
  • Recipient:
    • Twin: hypervolemia, polyuria, polyhydramnios, +/- hydrops fetalis, +/- CHF, hemolytic janundice, +/- large congested organs.
    • Placental disc: small, firm, congested.

Gross

  • Large vessels that connect the two umbilical cords.

Microscopic

Features:[19]

  • Artery-to-vein anatomosis - where artery and vein are associated with different umbilical cords.
  • Donor twin side of placenta:
    • Edematous villi.
    • Increased nucleated RBCs.
  • Recipient twin side of placenta:
    • Congested.

Diseases of the placental attachment

Placenta acreta/percreta/increta

Placenta attaches to the uterus deeper than it should.

Placental abruption

General

Classic clinical manifestations:[20]

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

Pathologic findings

Features:

  • Gross pathology: depression on maternal side, large blood clot.
    • Central haemorrhage is the most worrisome.

Note:

  • There are no good microscopic findings for placental abruption.

Infection

General[21]

  • Infection usually ascending, i.e. from vagina up through cervix.
    • Assoc. 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)[21]

  • Fetal membranes: chorioamnionitis, membranitis.[22]
  • Umbilical cord: funisitis.
  • Placenta: placentitis, villitis.

Grading infection (chorioamnionitis, membranitis, funisitis)

Membranitis:[22]

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

Chorioamnionitis:[22]

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

Sternberg separates vasculitis and funisitis without really explaining the terms[22] -- I presume: vasculitis = inflammation of vessels in the umbilical cord. funisitis = inflammation of the cord (vessels and Wharton jelly).

Umbilical cord vasculitis:[22]

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

Umbilical funisitis:[22]

  1. focal inflammation.
  2. diffuse inflammation.
  3. necrosis - in vessels or Wharton jelly.

Note: There is no such thing as chorionitis.[23]

Infarction

True infarcts

General

  • Associated with retroplacental hematoma.

Gross

Features:[24]

  • Early - red.
  • Late - white/grey.

Images:

Microscopic

Features:

  • Loss of intervillous space.[24]
    • Villi appear to be crowded.[25]
  • Prominent syncytial knots.
  • Thickened trophoblastic basement membrance (below cytotrophoblasts).
  • +/-Acute atherosis (vaguely like atherosclerosis).
    • Fibrioid necrosis.
    • Vessel wall lipid deposition.

Images:

Significant infarcts

  • > 3cm --or-- central location --or-- in 1st or 2nd trimester.
    • Small foci are accepted in term placentae - typically at periphery.

Perivillous fibrin deposition

  • Massive perivillous fibrin deposition is assoc. with anti-phospholipid antibody (APLA) syndrome.[27]
    • APLA is assoc. with recurrent miscarriage - can be treated with heparin + ASA.[27]
  • Thought to be an immunologic problem - resulting in platelet activation and fibrin deposition.[27]

Gross

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

Microscopy

  • Acellular eosinophilic material around formed villi.
    • Obliteration of intervillous space.

Other

Passage of meconium

General

  • Associated with fetal distress.

Gross

  • Green/green discolourization.

Microscopy

Features:[28]

  • Macrophages with brown fine granular pigment.
  • Columnar morphology (normally cuboidal).
  • "Drop-out" of individual cell -- the loss of individual cells.

Level of staining and time:[29]

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

DDx:

  • Hemosiderin-laden macrophages.

Images:

Special stains

  • Hemosiderin +ve in hemosiderin-laden macrophages.
  • PAS +ve in meconium-laden macrophages.[30]

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

  • Hemosiderin stain -- +ve for old blood.
    • Prussian-blue stain = hemosiderin stain.[31]
  • PAS-D -- +ve in chorioamnionitis???

Note:

  • Meconium contains bile.[32]

Maternal disease

Hypertensive changes

Features:[33]

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

Associated changes:[33]

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

Hypertrophic decidual vasculopathy

Features:[34]

  • 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[35] -- key feature.
  • Severe:[34]
    1. Atherosis of maternal blood vessels.
      • Foamy macrophages within vascular wall.
    2. Fibrinoid necrosis of vessel wall (amorphous eosinophilic material vessel wall).

General:

  • Seen in intrauterine growth restriction (IUGR).

Images:

HELLP syndrome

General

  • Diagnosed clinically.
  • Pathologically not the same as severe preclampsia.[36]

Definition:

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

Microscopic

Features:[37]

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

Tumours

Main article: Gestational trophoblastic disease

Chorangioma

General

Epidemiology

  • Often benign.
  • May be association with:
    • Fetal maternal haemorrhage.
    • Hydrops.
    • IUGR.

Microscopy

Features:

  • Mass of capillaries.

Image:

See also

References

  1. ↑ URL: http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5069. Accessed on: 7 July 2010.
  2. ↑ 2.0 2.1 2.2 2.3 Sternberg, Stephen S. (1997). Histology for Pathologists (2nd ed.). Lippincott Williams & Wilkins. pp. 974. ISBN 978-0397517183.
  3. ↑ Sternberg, Stephen S. (1997). Histology for Pathologists (2nd ed.). Lippincott Williams & Wilkins. pp. 977. ISBN 978-0397517183.
  4. ↑ J Anat. Soc. India 49(2) 149-152 (2000). Available at: http://www.indmedica.com/anatomy/aindex1.cfm?anid=41. Accessed on: January 21, 2009.
  5. ↑ Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 461. ISBN 978-0443066450.
  6. ↑ URL: http://medical-dictionary.thefreedictionary.com/amnion+nodosum. Accessed on: 18 November 2010.
  7. ↑ http://library.med.utah.edu/WebPath/PLACHTML/PLAC042.html
  8. ↑ AFIP Placental pathol. ISBN: 1-881041-89-1. P.312
  9. ↑ AFIP Placental pathol. ISBN: 1-881041-89-1. P.312
  10. ↑ 10.0 10.1 10.2 10.3 10.4 10.5 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 464. ISBN 978-0781765275.
  11. ↑ URL: http://www.glowm.com/?p=glowm.cml/section_view&articleid=151. Accessed on: 8 January 2011.
  12. ↑ 12.0 12.1 Hasegawa J, Farina A, Nakamura M, et al. (December 2010). "Analysis of the ultrasonographic findings predictive of vasa previa". Prenat. Diagn. 30 (12-13): 1121–5. doi:10.1002/pd.2618. PMID 20872421.
  13. ↑ 13.0 13.1 Airas U, Heinonen S (April 2002). "Clinical significance of true umbilical knots: a population-based analysis". Am J Perinatol 19 (3): 127–32. doi:10.1055/s-2002-25311. PMID 12012287.
  14. ↑ 14.0 14.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 464. ISBN 978-0781765275.
  15. ↑ Khong TY (December 2010). "Evidence-based pathology: umbilical cord coiling". Pathology 42 (7): 618–22. doi:10.3109/00313025.2010.520309. PMID 21080869.
  16. ↑ PMID 16076615.
  17. ↑ Sternberg, Stephen S. (1997). Histology for Pathologists (2nd ed.). Lippincott Williams & Wilkins. pp. 979. ISBN 978-0397517183.
  18. ↑ 18.0 18.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 469. ISBN 978-0781765275.
  19. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 469-70. ISBN 978-0781765275.
  20. ↑ Tikkanen M, Nuutila M, Hiilesmaa V, Paavonen J, Ylikorkala O (2006). "Clinical presentation and risk factors of placental abruption". Acta Obstet Gynecol Scand 85 (6): 700–5. doi:10.1080/00016340500449915. PMID 16752262.
  21. ↑ 21.0 21.1 Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1106. ISBN 0-7216-0187-1.
  22. ↑ 22.0 22.1 22.2 22.3 22.4 22.5 Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 2311. ISBN 978-0781740517.
  23. ↑ ALS. February 2009.
  24. ↑ 24.0 24.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 465. ISBN 978-0781765275.
  25. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1109. ISBN 0-7216-0187-1.
  26. ↑ URL: http://path.upmc.edu/cases/case75/micro.html. Accessed on: 6 January 2011.
  27. ↑ 27.0 27.1 27.2 Sebire NJ, Backos M, Goldin RD, Regan L (May 2002). "Placental massive perivillous fibrin deposition associated with antiphospholipid antibody syndrome". BJOG 109 (5): 570–3. PMID 12066949. http://www3.interscience.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1470-0328&date=2002&volume=109&issue=5&spage=570.
  28. ↑ ALS. 6 Feb 2009.
  29. ↑ 3 Apr 2009.
  30. ↑ Povýsil C, Bennett R, Povýsilová V (January 2001). "CD 68 positivity of the so-called meconium corpuscles in human foetal intestine". Cesk Patol 37 (1): 7–9. PMID 11268705.
  31. ↑ Sienko A, Altshuler G (September 1999). "Meconium-induced umbilical vascular necrosis in abortuses and fetuses: a histopathologic study for cytokines". Obstet Gynecol 94 (3): 415?0. PMID 10472870.
  32. ↑ Sienko A, Altshuler G (September 1999). "Meconium-induced umbilical vascular necrosis in abortuses and fetuses: a histopathologic study for cytokines". Obstet Gynecol 94 (3): 415?0. PMID 10472870.
  33. ↑ 33.0 33.1 Soma H, Yoshida K, Mukaida T, Tabuchi Y (1982). "Morphologic changes in the hypertensive placenta". Contrib Gynecol Obstet 9: 58–75. PMID 6754249.
  34. ↑ 34.0 34.1 Roberts, DJ.; Post, MD. (Dec 2008). "The placenta in pre-eclampsia and intrauterine growth restriction.". J Clin Pathol 61 (12): 1254-60. doi:10.1136/jcp.2008.055236. PMID 18641412.
  35. ↑ AFIP - Placental Pathology. P.122. ISBN: 1-881041-89-1. 2004.
  36. ↑ Vinnars MT, Wijnaendts LC, Westgren M, Bolte AC, Papadogiannakis N, Nasiell J (May 2008). "Severe preeclampsia with and without HELLP differ with regard to placental pathology". Hypertension 51 (5): 1295–9. doi:10.1161/HYPERTENSIONAHA.107.104844. PMID 18362224.
  37. ↑ Ornstein MH, Rand JH (July 1994). "An association between refractory HELLP syndrome and antiphospholipid antibodies during pregnancy; a report of 2 cases". J. Rheumatol. 21 (7): 1360–4. PMID 7966086.
  38. ↑ Amer HZ, Heller DS (2010). "Chorangioma and related vascular lesions of the placenta--a review". Fetal Pediatr Pathol 29 (4): 199–206. doi:10.3109/15513815.2010.487009. PMID 20594143.

External links

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