Gestational trophoblastic disease

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

Overview

Most common

Overview of gestational trophoblastic disease:

Type of mole Gross Nuclear atypia Chorionic villi IHC DNA content Micrographs
Complete mole "snowstorm" +/- ? yes, all abnormal p57(KIP2) -ve Paternal, diploid complete mole + intermed. trophoblast (WC), complete mole (WC)
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 (webpathology.com)

More comprehensive overview

Benign abnormal looking placenta:

Abnormal fertilization:

Tumours:

Entities

Choriocarcinoma

Main article: Choriocarcinoma

Hydatidiform moles

General

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

Etymology:

  • Hydatid is literally watery vesicle.[1]

Types

  1. Partial mole - see partial mole.
  2. Complete mole - see complete mole.

Extent:

  • Invasive mole - not a subtype.
    • Within uterine muscle +/- vessels.

Microscopic

Hydropic changes:

Entity Chorionic villi (outline) Cisterns Blood vessels Nucleated RBCs p57 / Ki-67[2] staining ‡ Ploidy Micrograph
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]

Note:

  • ‡ The amount of Ki-67 staining varies considerably based on what one reads. Chen at al.[3] suggest 25% versus 5% for partial mole versus hydropic abortus.

Mole versus normal

Non-molar versus partial versus complete - short version

Features:[5]

  • 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 lack the maternal genome; thus, p57(KIP2) immunostaining (in the cytotrophoblasts and villous stromal cells) is absent.[6][7]
      • Intermediate trophoblasts and maternal tissue are positive controls.[7]
    • Memory device:
      • p57 is positive in partial moles.
      • 3 Ps - partial moles are triploid.

Molecular

Partial hydatidiform mole

  • AKA partial mole.

General

Genetics:

  • Usually triploid (e.g. 69XXY).

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.
    • Without atypia.[9]
  • "Norwegian fjord periphery"[10] - jagged border / irregular sawtooth-like periphery.
    • Complete moles tend to have a smooth border

DDx:

Images:

IHC

Features:[11]

  • Ki-67 ~ 25+/-5% of cytotrophoblasts and intermediate trophoblasts.
    • Hydropic abortus ~ 5+/-1%.
  • p53 ~ 22+/-12% of cytotrophoblasts and intermediate trophoblasts.
    • Hydropic abortus ~ 5+/-3%.

Complete hydatidiform mole

  • AKA complete mole, AKA classic mole.

General

Epidemiology:

Genetics:

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

Gross/Radiology

  • "Snowstorm" appearance on ultrasound.[13]
  • May be described as "grape-like" on gross exam.[14]

Image:

Microscopic

Features:

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

Images

  • Complete mole and intermediate trophoblast - intermed. mag. (WC)

  • Complete mole - low mag. (WC)

  • Complete mole - high mag. (WC)

Invasive hydatidiform mole

  • AKA invasive mole.
  • AKA chorioadenoma destruens.[15]

General

Microscopic

Features:

  • Chorionic villi - abnormal +/- normal.
  • Trophoblastic cells within uterine muscle +/- vessels - key feature.

DDx:

Images

  • Invasive mole - very low mag. (WC)

  • Invasive mole - low mag. (WC)

  • Invasive mole - intermed. mag. (WC)

  • Invasive mole - high mag. (WC)

  • Invasive mole - very high mag. (WC)

Entities - intermediate trophoblast

Entity Key feature Other histologic features IHC DDx Other Image
Placental site nodule (PSN) paucicellular, hyaline material no mitotic activity p16 -ve, MIB1 low EPS, squamous carcinoma post-partum
PSN. (WC)
(ijpmonline.org)
Exaggerated placental site (EPS) abundant intermediate trophoblasts - between muscle no mitotic activity MIB1 ~0% PSTT, PSN post-partum Image?
Placental site trophoblastic tumour (PSTT) abundant cytoplasm - not clear, dyscohesive +/-multinucleation MIB1 high, p63 -ve, CD146 +ve EPS, choriocarcinoma Other? (webpathology.com)
Epithelioid trophoblastic tumour (ETT) nests of cells in hyaline stroma eosinophilic cytoplasm, central nucleus MIB1 low, p63 +ve, CD146 -ve squamous carcinoma Other? (webpathology.com)
Choriocarcinoma polygonal cells with clear cytoplasm (cytotrophoblasts) multinucleated cells with smudged nuclei (syncytiotrophoblasts), no chorionic villi beta-hCG +ve, p63 +ve invasive hydatidiform mole, PSTT elevated beta-hCG (serum); not intermediate trophoblast derived.
Choriocarcinoma. (WC)
(webpathology.com)

Placental site nodule

  • Abbreviated PSN.

General

  • Benign.
  • Intermediate trophoblast remnants from a previous gestation.[16]
  • Usually an incidental finding.

Clinical:

  • Usually asymptomatic.
  • Vaginal bleeding. (?)
  • Infertility. (?)

Microscopic

Features:[16]

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

Notes:

  • No mitotic activity.

DDx:

Images

  • PSN - intermed. mag. (WC)

  • PSN - high mag. (WC)

www:

IHC

Features:[16]

  • Inhibin alpha +ve.
  • CK18 +ve.
  • MIB1 low.

Other:

  • p16 -ve.

Exaggerated placental site

  • Abbreviated EPS.

General

  • Benign.

Definition:

Note:

  • Used to go by a terrible old term: syncytial endometritis:[17]
    • Not syncytial -- mostly.
    • Not inflammatory.

Microscopic

Features:[17]

  • 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.
  • Ectatic blood vessels.

DDx:

IHC

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

Placental site trophoblastic tumour

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

General

  • Derived from intermediate trophoblast.
  • Follows pregnancy.
  • May be associated with nephrotic syndrome[18] with granular IgM staining.[19]

Clinical:

  • Raised (serum) beta-hCG - but usually not has high as in choriocarcinoma.
    • In ~70% < 1000 IU/L.[20]
    • In a series of 55 cases the average beta-hCG was ~700 IU/L.[21]
  • Prognosis dependent on time of diagnosis from last pregnancy.
    • <48 months = good prognosis.[20]

Microscopic

Features:

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

Note:

DDx:

Images:

IHC

Features:[23]

  • CD146 +ve.
  • p63 -ve.
  • Ki-67 ~14+/-7%.
    • Choriocarcinoma ~69+/-20%.

Epithelioid trophoblastic tumour

  • Abbreviated ETT.

General

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

Clinical:

  • Vaginal bleeding.
  • Elevated beta-hCG.

Gross

Features:[24]

  • Solid mass.
  • Flesh-like appearance.

Image:

Microscopic

Features:[25]

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

DDx:

Images:

IHC

Features:[26]

  • Cyclin E +ve (nuclear).
  • p16 -ve.
    • +ve (nuclear) in squamous cell carcinoma of the cervix.

Others:

  • HMCK -ve.
    • SCC +ve.

Note:

  • p63 not useful... +ve in both SCC and ETT.

See also

References

  1. ↑ URL: http://dictionary.reference.com/browse/hydatid.
  2. ↑ URL: http://www.ihcworld.com/_newsletter/2003/focus_mar_2003.pdf. Accessed on: 28 May 2011.
  3. ↑ Chen, Y.; Shen, D.; Gu, Y.; Zhong, P.; Xie, J.; Song, Q. (Mar 2012). "The diagnostic value of Ki-67, P53 and P63 in distinguishing partial Hydatidiform mole from hydropic abortion.". Wien Klin Wochenschr 124 (5-6): 184-7. doi:10.1007/s00508-011-0119-4. PMID 22218717.
  4. ↑ URL: http://pathologyoutlines.com/placenta.html#hydatgeneral.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 7.0 7.1 Fukunaga, M. (Dec 2002). "Immunohistochemical characterization of p57(KIP2) expression in early hydatidiform moles.". Hum Pathol 33 (12): 1188-92. doi:10.1053/hupa.2002.129421. PMID 12514787.
  8. ↑ http://jcp.bmjjournals.com/cgi/reprint/51/6/438.pdf
  9. ↑ URL: http://pathologyoutlines.com/placenta.html#incompletemole. Accessed on: 9 August 2011.
  10. ↑ 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.
  11. ↑ Chen, Y.; Shen, D.; Gu, Y.; Zhong, P.; Xie, J.; Song, Q. (Mar 2012). "The diagnostic value of Ki-67, P53 and P63 in distinguishing partial Hydatidiform mole from hydropic abortion.". Wien Klin Wochenschr 124 (5-6): 184-7. doi:10.1007/s00508-011-0119-4. PMID 22218717.
  12. ↑ 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.
  13. ↑ URL:http://www.jultrasoundmed.org/cgi/content/abstract/18/9/589. Accessed on: 27 July 2010.
  14. ↑ Abike, F.; Temizkan, O.; Payasli, A.; Avsar, F.; Karahan, N.; Baspinar, S. (Jan 2008). "Postmenopausal complete hydatidiform mole: a case report.". Maturitas 59 (1): 95-8. doi:10.1016/j.maturitas.2007.10.005. PMID 18162339.
  15. ↑ McDonald, TW.; Ruffolo, EH. (Feb 1983). "Modern management of gestational trophoblastic disease.". Obstet Gynecol Surv 38 (2): 67-83. PMID 6300738.
  16. ↑ 16.0 16.1 16.2 16.3 16.4 16.5 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.
  17. ↑ 17.0 17.1 URL: http://moon.ouhsc.edu/kfung/IACP-OLP/TC-Text/TC-01-Supp.pdf. Accessed on: 15 August 2011.
  18. ↑ Bonazzi, C.; Urso, M.; Dell'Anna, T.; Sacco, S.; Buda, A.; Cantú, MG. (Aug 2004). "Placental site trophoblastic tumor: an overview.". J Reprod Med 49 (8): 585-8. PMID 15457847.
  19. ↑ Komatsuda, A.; Nakamoto, Y.; Asakura, K.; Yasuda, T.; Imai, H.; Miura, AB. (May 1992). "Case report: nephrotic syndrome associated with a total hydatidiform mole.". Am J Med Sci 303 (5): 309-12. PMID 1580319.
  20. ↑ 20.0 20.1 Schmid, P.; Nagai, Y.; Agarwal, R.; Hancock, B.; Savage, PM.; Sebire, NJ.; Lindsay, I.; Wells, M. et al. (Jul 2009). "Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study.". Lancet 374 (9683): 48-55. doi:10.1016/S0140-6736(09)60618-8. PMID 19552948.
  21. ↑ Baergen, RN.; Rutgers, JL.; Young, RH.; Osann, K.; Scully, RE. (Mar 2006). "Placental site trophoblastic tumor: A study of 55 cases and review of the literature emphasizing factors of prognostic significance.". Gynecol Oncol 100 (3): 511-20. doi:10.1016/j.ygyno.2005.08.058. PMID 16246400.
  22. ↑ URL: http://www.webpathology.com/image.asp?n=3&Case=588. Accessed on: 1 January 2012.
  23. ↑ Shih, IM.; Kurman, RJ. (Jan 1998). "Ki-67 labeling index in the differential diagnosis of exaggerated placental site, placental site trophoblastic tumor, and choriocarcinoma: a double immunohistochemical staining technique using Ki-67 and Mel-CAM antibodies.". Hum Pathol 29 (1): 27-33. PMID 9445130.
  24. ↑ 24.0 24.1 Fadare, O.; Parkash, V.; Carcangiu, ML.; Hui, P. (Jan 2006). "Epithelioid trophoblastic tumor: clinicopathological features with an emphasis on uterine cervical involvement.". Mod Pathol 19 (1): 75-82. doi:10.1038/modpathol.3800485. PMID 16258513.
  25. ↑ 25.0 25.1 URL: http://www.webpathology.com/image.asp?case=589&n=2. Accessed on: 15 August 2011.
  26. ↑ Mao, TL.; Seidman, JD.; Kurman, RJ.; Shih, IeM. (Sep 2006). "Cyclin E and p16 immunoreactivity in epithelioid trophoblastic tumor--an aid in differential diagnosis.". Am J Surg Pathol 30 (9): 1105-10. doi:10.1097/01.pas.0000209854.28282.87. PMID 16931955.
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