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 paucicellular, hyaline material no mitotic activity IHC? EPS ??? post-partum (ijpmonline.org)
Exaggerated placental site abundant intermediate trophoblasts - between muscle no mitotic activity MIB1 ~0% PSTT, PSN post-partum Image?
Placental site trophoblastic tumour abundant cytoplasm - not clear +/-multinucleation MIB1 high EPS Other? (webpathology.com)
Epithelioid trophoblastic tumour nests of cells in hyaline stroma eosinophilic cytoplasm, central nucleus p16-, MIB1 low squamous carcinoma Other? (webpathology.com)
Choriocarcinoma polygonal cells with clear cytoplasm (cytotrophoblasts) multinucleated cells with smudged nuclei (syncytiotrophoblasts), no chorionic villi beta-hCG DDx? elevated beta-hCG (serum) (webpathology.com)

Placental site nodule

  • Abbreviated PSN.

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 15.3 15.4 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.
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