Gestational trophoblastic disease

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Gestational trophoblastic disease (GTD) includes choriocarcinoma and hydatidiform moles.

Overview

Most common

Overview of gestational trophoblastic disease:

Gross Nuclear atypia Villi IHC DNA content Images
Complete mole "snowstorm" +/- ? yes, all abnormal [1] p57(KIP2) -ve Paternal, diploid Complete mole (pathconsultddx.com)
Partial mole grape-like
clusters 		+/- large villi, villi with cisterns,
villi with cytotrophoblastic inclusions 		p57(KIP2) +ve Maternal & paternal, tripoid Partial mole (utah.edu)
Choriocarcinoma haemorrahagic, necrotic marked none beta-hCG +ve ? Choriocarcinoma - testicular (webpathology.com)

More comprehensive overview

Benign abnormal looking placenta:

  • Placental site nodule (PSN).
  • Exaggerated placental site (EPS).

Abnormal fertilization:

  • Hydatidiform mole.

Tumours:

  • Invasive mole.
  • Choriocarcinoma.
  • Placental site trophoblastic tumour (PSTT).
  • Epithelioid trophoblastic tumour (ETT).

Choriocarcinoma

General

Clinical/Epidemiology

  • High beta-hCG.
  • May be preceded by a complete hydatidiform mole.[2]
  • More common in the far east.
  • More common at extremes of fertile age (teens and 40-50 years).

Microscopic

Features:

  • Nuclear pleomorphism - usually marked.
  • Often haemorrhage.
  • Syncytiotrophoblast surrounds nests of cytotrophoblast.

Image:

Notes:

  • Its usually NOT choriocarcinoma if there are villi.[3]

IHC

  • beta-hCG +ve.[4]

Hydatidiform moles

General

  • Non-neoplastic proliferation.
  • Significance: increased risk for choriocarcinoma (in complete moles).

Etymology:

  • Hydatid is literally watery vesicle.[5]

Types

  • Partial mole.
    • Triploid.
    • Choriocarcinoma extremely rare.
  • Complete mole.
    • Diploid or tetraploid.
    • "Empty" egg fertilized, ergo paternal DNA.
    • Risk for choriocarcinoma; memory device complete -> choriocarcinoma.

Microscopic

Partial

Features:

  • Scant trophoblastic proliferation.
    • May form finger-like projections.
  • Fetal tissue.
    • Nucleated RBCs common.

Complete

Features:

  • Cisterns usu. well-developed.
    • Large empty areas within trophoblastic tissue.
  • Rarely nucleated RBCs.
  • Canalicular (thin) blood vessels.

Mole vs. normal

IHC

  • p57(KIP2) - the gene is strongly paternally imprinted and the paternal copy is inactived; its expression is from the maternal gene.
    • Complete moles lacks the maternal genome; thus, p57(KIP2) immunostaining is absent.[7]
    • Memory device:
      • p57 is positive in partial moles.
      • 3 Ps - partial moles are triploid.

Molecular

Partial Mole

  • Formal name: partial hydatidiform mole.

Genetics

  • Polypoid - usually triploid (e.g. 69XXY).

Images: [1]

Histology

  • Abnormal chorionic villi.
    • Villi too large (>0.1 mm ?).
    • Villi with cisterns.
      • Contain fluid in the centre, i.e. are "hydropic".
    • Villi with cytotrophoblastic inclusions.
      • Cytotrophoblast in the core of a villus (normally it is only at the surface of the villus).
  • May have fetal parts, such as nucleated RBCs.
  • Trophoblastic proliferation - image - med.utah.edu.
    • Without atypia.[9]

Images:

Complete Mole

  • Formal name: complete hydatidiform mole.
  • Also known as classic mole.

Epidemiology

Genetics

  • Diploid - most are 46XX.
  • All male dervived, i.e. arise from DNA in sperm.

Microscopy

  • No normal villi.
  • No fetal parts seen.

Image:

Radiology

  • "Snowstorm" appearance on ultrasound.[11]

Placental site trophoblastic tumour

  • Abbreviated PSTT.
  • Malignant counterpart of exaggerated placental site or EPS.

Clinical

  • Raised beta-hCG - but usually not has high as in choriocarcinoma.[12]
  • Derived from trophoblast - the stuff that forms the chorionic villi - remember: syncytiotrophoblasts (outer layer) and cytotrophoblasts (inner layer).

Epidemiology

  • Usually follows a normal pregnancy ~ 75% of cases.[12]

Microscopic

Features:

  • Large cells.
  • Nuclear atypia.
  • Cytoplasm - cytoplasmic.
  • NC ratio ~ normal.

EPS vs. PSTT:

  • EPS has a low MIB-1 (Ki-67).

Epithelioid trophoblastic tumour

  • Abbreviated ETT.
  • Often in endocervix.
  • Malignant counterpart of placental site nodule or PSN.

Images:

DDx:

Placental site nodule

General

  • Benign.

Microscopic

Features:

  • Small collection of cells that look similar to decidua (mnemonic NEW):
    • Nucleus, central location.
    • Eosinophilic cytoplasm.
    • Well-defined cell borders.

Images:

DDx:

See also

References

  1. ↑ http://pathologyoutlines.com/placenta.html#completemole
  2. ↑ 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. 1110-1111. ISBN 0-7216-0187-1.
  3. ↑ Notebook P.180. 21 September 2009.
  4. ↑ Kalhor N, Ramirez PT, Deavers MT, Malpica A, Silva EG (April 2009). "Immunohistochemical studies of trophoblastic tumors". Am. J. Surg. Pathol. 33 (4): 633–8. doi:10.1097/PAS.0b013e318191f2eb. PMID 19145204.
  5. ↑ URL: http://dictionary.reference.com/browse/hydatid.
  6. ↑ URL: http://pathologyoutlines.com/placenta.html#hydatgeneral.
  7. ↑ Merchant SH, Amin MB, Viswanatha DS, Malhotra RK, Moehlenkamp C, Joste NE (February 2005). "p57KIP2 immunohistochemistry in early molar pregnancies: emphasis on its complementary role in the differential diagnosis of hydropic abortuses". Hum. Pathol. 36 (2): 180–6. doi:10.1016/j.humpath.2004.12.007. PMID 15754295.
  8. ↑ http://jcp.bmjjournals.com/cgi/reprint/51/6/438.pdf
  9. ↑ http://pathologyoutlines.com/placenta.html#incompletemole
  10. ↑ 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. 1111. ISBN 0-7216-0187-1.
  11. ↑ URL:http://www.jultrasoundmed.org/cgi/content/abstract/18/9/589. Accessed on: 27 July 2010.
  12. ↑ 12.0 12.1 URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70463-6. Accessed on: 23 September 2009.
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