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:

Abnormal fertilization:

Tumours:

Entities

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

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

Etymology:

  • Hydatid is literally watery vesicle.[5]

Types

Microscopic

Hydropic changes:

Entity Villi (outline) Cisterns Blood vessels Nucleated RBCs p57 / Ki-67[6] staining Ploidy Image
Complete mole bizarre; often not ovoid; fissures/slit-like gaps well-developed canalicular (thin walled) / few (???) rare -ve / ~70% diploid / tetraploid [1], [2], [3], [4]
Partial mole jagged, still quasi ovoid poorly developed / small present common +ve / ~70% triploid [5], [6]
Hydropic abortus smooth poorly developed / small common common +ve / ~20% diploid [7]

Mole vs. normal

Non-molar vs. partial vs. complete - short version

Features:[8]

  • Non-molar pregnancy: polar proliferation of trophoblastic tissue.
  • Partial mole: Norwegian fjord periphery, circumferential or multifocal trophoblastic proliferation, fetal parts.
  • Complete mole: grapes grossly, large villi with round borders.

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.[9]
    • Memory device:
      • p57 is positive in partial moles.
      • 3 Ps - partial moles are triploid.

Molecular

Partial Mole

  • Formal name: partial hydatidiform mole.

General

Genetics:

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

Images: [8]

Microscopic

Features:

  • 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.
  • "Norwegian fjord periphery"[12] - jagged border / irregular sawtooth-like periphery.
    • Complete moles tend to have a smooth border

Images:

Complete Mole

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

General

Epidemiology:

Genetics:

  • Diploid - most are 46XX.
  • Male derived, i.e. arise from DNA in sperm; empty egg fertilized.

Radiology

  • "Snowstorm" appearance on ultrasound.[14]

Microscopic

Features:

  • No normal villi.
  • No fetal parts seen.
    • Very rarely nucleated RBCs.

Image:

Entities - intermediate trophoblast

Entity Key feature Other histologic features IHC DDx Other Image
Placental site nodule Key feature? Other histologic features? IHC? DDx? Other? Image?
Exaggerated placental site Key feature? Other histologic features? MIB1 ~0% PSTT Other? Image?
Placental site trophoblastic tumour abundant cytoplasm - not clear +/-multinucleation MIB1 high EPS Other? Image?
Epithelioid trophoblastic tumour nests of cells in hyaline stroma eosinophilic cytoplasm, central nucleus p16-, MIB1 low squamous carcinoma Other? Image?
Choriocarcinoma polygonal cells with clear cytoplasm (cytotrophoblasts) multinucleated cells with smudged nuclei (syncytiotrophoblasts), no chorionic villi beta-hCG DDx? elevated beta-hCG (serum) Image?

Placental site nodule

General

  • Benign.
  • Intermediate trophoblast remnants from a previous gestation.[15]

Microscopic

Features:[15]

  • Paucicellular with hyaline material scattered cells.
  • Variable cell population:
    • Small-large cells.
    • Clear to eosinophilic cytoplasm.
    • +/-Multinucleation.

Notes:

  • No mitotic activity.

Images:

DDx:

Exaggerated placental site

  • Abbreviated EPS.

General

  • Benign.

Definition:

Note:

  • Used to go by a terrible old term: syncytial endometritis:[16]
    • Not syncytial -- mostly.
    • Not inflammatory.

Microscopic

Features:[16]

  • Intermediate trophoblast:
    • Abundant (eosinophilic) cytoplasm.
  • Usu. adjacent to:
    • Chorionic villi.
    • Decidua - endometrial stromal cells with a nucleus central, eosinphilic cytoplasm, well-defined cell borders.
  • No mitotic activity.

DDx:

IHC

  • MIB1 ~0%.
    • Used to differentiate from PSTT.

Placental site trophoblastic tumour

  • Abbreviated PSTT.
  • Malignant counterpart of exaggerated placental site (abbreviated EPS).

General

Clinical

  • Raised beta-hCG - but usually not has high as in choriocarcinoma.[17]
  • 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.[17]

Microscopic

Features:

  • Large cells.
  • Nuclear pleomorphism.
  • Cytoplasm:
    • Abundant.
    • Solid, i.e. not vesicular.
    • Light basophilic, not clear - key feature.
  • NC ratio ~ normal.
  • +/-Multinucleated cells.

DDx:

EPS vs. PSTT:

  • EPS has a low MIB1 (Ki-67).

Images:

Epithelioid trophoblastic tumour

  • Abbreviated ETT.

General

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

Clinical:

  • Vaginal bleeding.
  • Elevated beta-hCG.

Microscopic

Features:[18]

  • Architecture: nests in hyaline matrix.
  • Cytoplasm: abundant, eosinophilic.

DDx:

Images:

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://www.ihcworld.com/_newsletter/2003/focus_mar_2003.pdf. Accessed on: 28 May 2011.
  7. URL: http://pathologyoutlines.com/placenta.html#hydatgeneral.
  8. Howat, AJ.; Beck, S.; Fox, H.; Harris, SC.; Hill, AS.; Nicholson, CM.; Williams, RA. (Jul 1993). "Can histopathologists reliably diagnose molar pregnancy?". J Clin Pathol 46 (7): 599-602. PMID 8157742.
  9. 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.
  10. http://jcp.bmjjournals.com/cgi/reprint/51/6/438.pdf
  11. URL: http://pathologyoutlines.com/placenta.html#incompletemole. Accessed on: 9 August 2011.
  12. Howat, AJ.; Beck, S.; Fox, H.; Harris, SC.; Hill, AS.; Nicholson, CM.; Williams, RA. (Jul 1993). "Can histopathologists reliably diagnose molar pregnancy?". J Clin Pathol 46 (7): 599-602. PMID 8157742. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC501384/?page=3.
  13. 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.
  14. URL:http://www.jultrasoundmed.org/cgi/content/abstract/18/9/589. Accessed on: 27 July 2010.
  15. 15.0 15.1 15.2 Jacob, S.; Mohapatra, D.. "Placental site nodule: a tumor-like trophoblastic lesion.". Indian J Pathol Microbiol 52 (2): 240-1. PMID 19332926. http://www.ijpmonline.org/text.asp?2009/52/2/240/48931.
  16. 16.0 16.1 URL: http://moon.ouhsc.edu/kfung/IACP-OLP/TC-Text/TC-01-Supp.pdf. Accessed on: 15 August 2011.
  17. 17.0 17.1 URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70463-6. Accessed on: 23 September 2009.
  18. 18.0 18.1 URL: http://www.webpathology.com/image.asp?case=589&n=2. Accessed on: 15 August 2011.