Difference between revisions of "Gestational trophoblastic disease"

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'''Gestational trophoblastic disease''' (GTD) includes [[choriocarcinoma]] and hydatidiform moles.
'''Gestational trophoblastic disease''' (abbreviated '''GTD'''), also '''gestational trophoblastic neoplasia''' (abbreviated '''GTN'''), includes [[choriocarcinoma]] and hydatidiform moles.


=Overview=
=Overview=
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! Type of mole
! Type of mole
! Gross
! Gross
! Nuclear atypia
! [[Nuclear atypia]]
! [[Chorionic villi]]
! [[Chorionic villi]]
! [[IHC]]
! [[IHC]]
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| beta-hCG +ve
| beta-hCG +ve
| ?
| ?
| [http://www.webpathology.com/image.asp?case=36&n=1 choriocarcinoma (webpathology.com)]
| [[Image:Choriocarcinoma_-2-_very_high_mag.jpg|thumb|center|120px|Choriocarcinoma. (WC)]]
|-
|-
|}
|}
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|}
|}
Note:
Note:
* ‡ The amount of Ki-67 staining varies considerably based on what one reads. Chen ''at al.''<ref>{{Cite journal  | last1 = Chen | first1 = Y. | last2 = Shen | first2 = D. | last3 = Gu | first3 = Y. | last4 = Zhong | first4 = P. | last5 = Xie | first5 = J. | last6 = Song | first6 = Q. | title = The diagnostic value of Ki-67, P53 and P63 in distinguishing partial Hydatidiform mole from hydropic abortion. | journal = Wien Klin Wochenschr | volume = 124 | issue = 5-6 | pages = 184-7 | month = Mar | year = 2012 | doi = 10.1007/s00508-011-0119-4 | PMID = 22218717 }}</ref> suggest 25% versus 5% for partial mole versus hydropic abortus.
* ‡ The amount of [[Ki-67]] staining varies considerably based on what one reads. Chen ''at al.''<ref>{{Cite journal  | last1 = Chen | first1 = Y. | last2 = Shen | first2 = D. | last3 = Gu | first3 = Y. | last4 = Zhong | first4 = P. | last5 = Xie | first5 = J. | last6 = Song | first6 = Q. | title = The diagnostic value of Ki-67, P53 and P63 in distinguishing partial Hydatidiform mole from hydropic abortion. | journal = Wien Klin Wochenschr | volume = 124 | issue = 5-6 | pages = 184-7 | month = Mar | year = 2012 | doi = 10.1007/s00508-011-0119-4 | PMID = 22218717 }}</ref> suggest 25% versus 5% for partial mole versus hydropic abortus.


====Mole versus normal====
====Mole versus normal====
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====Non-molar versus partial versus complete - short version====
====Non-molar versus partial versus complete - short version====
Features:<ref name=pmid8157742>{{Cite journal  | last1 = Howat | first1 = AJ. | last2 = Beck | first2 = S. | last3 = Fox | first3 = H. | last4 = Harris | first4 = SC. | last5 = Hill | first5 = AS. | last6 = Nicholson | first6 = CM. | last7 = Williams | first7 = RA. | title = Can histopathologists reliably diagnose molar pregnancy? | journal = J Clin Pathol | volume = 46 | issue = 7 | pages = 599-602 | month = Jul | year = 1993 | doi =  | PMID = 8157742 }}</ref>
Features:<ref name=pmid8157742>{{Cite journal  | last1 = Howat | first1 = AJ. | last2 = Beck | first2 = S. | last3 = Fox | first3 = H. | last4 = Harris | first4 = SC. | last5 = Hill | first5 = AS. | last6 = Nicholson | first6 = CM. | last7 = Williams | first7 = RA. | title = Can histopathologists reliably diagnose molar pregnancy? | journal = J Clin Pathol | volume = 46 | issue = 7 | pages = 599-602 | month = Jul | year = 1993 | doi =  | PMID = 8157742 | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC501384/?page=3 }}</ref>
*Non-molar pregnancy: polar proliferation of trophoblastic tissue.
*Non-molar pregnancy: polar proliferation of trophoblastic tissue.
*Partial mole: Norwegian fjord periphery, circumferential or multifocal trophoblastic proliferation, fetal parts.
*Partial mole: Norwegian fjord periphery, circumferential or multifocal trophoblastic proliferation, fetal parts.
Line 134: Line 134:
===Molecular===
===Molecular===
*The type of mole can be determined by [[cytogenetics]].<ref>[http://jcp.bmjjournals.com/cgi/reprint/51/6/438.pdf http://jcp.bmjjournals.com/cgi/reprint/51/6/438.pdf]</ref>
*The type of mole can be determined by [[cytogenetics]].<ref>[http://jcp.bmjjournals.com/cgi/reprint/51/6/438.pdf http://jcp.bmjjournals.com/cgi/reprint/51/6/438.pdf]</ref>
==Hydropic abortus==
===General===
*May be seen in the context of a previously detected fetal heart beat.
===Microsopic===
Features:
*Enlarged chorionic villi with some cisterns.
DDx:<ref>{{cite journal |authors=Rios-Doria E, Pennington KP, Reiter DJ, Parker EU |title=Diagnostic challenges in differentiating between hydropic abortus, and complete and partial hydatidiform molar pregnancies in early gestation |journal=Int J Gynecol Cancer |volume=33 |issue=9 |pages=1482–1484 |date=September 2023 |pmid=37268312 |doi=10.1136/ijgc-2022-004104 |url=}}</ref>
*Molar pregnancy.
===Sign out===
<pre>
Submitted as "Retained Products of Conception":
- Small and large chorionic villi with cisterns, suggestive of hydropic abortus, see comment.
- Benign decidual tissue present.
- Negative for evidence of fetal tissue in sampled tissue, see comment.
 
Comment:
Imaging previously described a gestational sac and a fetal heart beat. 
</pre>


==Partial hydatidiform mole==
==Partial hydatidiform mole==
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==Placental site nodule==
==Placental site nodule==
*Abbreviated ''PSN''.
*Abbreviated ''PSN''.
*''Implantation site'' redirects here.
{{Main|Placental site nodule}}
{{Main|Placental site nodule}}


==Exaggerated placental site==
==Exaggerated placental site==
*Abbreviated ''EPS''.
*Abbreviated ''EPS''.
 
*Previously known as ''syncytial endometritis''.<ref>URL: [http://www.webpathology.com/image.asp?case=565&n=7 http://www.webpathology.com/image.asp?case=565&n=7]. Accessed on: 22 May 2014.</ref>
===General===
{{Main|Exaggerated placental site}}
*Benign.
 
Definition:
*"Increased number" of implantation-site [[Intermediate trophoblast|intermediate trophoblastic cells]].
 
Note:
*Used to go by a terrible old term: ''syncytial endometritis'':<ref name=ouhsc_kfung>URL: [http://moon.ouhsc.edu/kfung/IACP-OLP/TC-Text/TC-01-Supp.pdf http://moon.ouhsc.edu/kfung/IACP-OLP/TC-Text/TC-01-Supp.pdf]. Accessed on: 15 August 2011.</ref>
**Not syncytial -- mostly.
**Not inflammatory.
===Microscopic===
Features:<ref name=ouhsc_kfung/>
*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:
*[[PSTT]].
 
===IHC===
*MIB1 ~0%.
**Used to differentiate from [[PSTT]].


==Placental site trophoblastic tumour==
==Placental site trophoblastic tumour==
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Image:
Image:
*[http://www.nature.com/modpathol/journal/v19/n1/fig_tab/3800485f1.html#figure-title ETT (nature.com)].<ref name=pmid16258513/>


===Microscopic===
===Microscopic===
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Images:
Images:
*[http://www.webpathology.com/image.asp?case=589&n=2 ETT (webpathology.com)].<ref name=webp_ett/>
*[http://www.webpathology.com/image.asp?case=589&n=2 ETT (webpathology.com)].<ref name=webp_ett/>
*[http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=12&cat3=861&stype=d ETT - several images (gfmer.ch)].


===IHC===
===IHC===
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[[Category:Gynecologic pathology]]
[[Category:Gynecologic pathology]]
[[Category:Gestational trophoblastic disease]]

Latest revision as of 22:07, 7 December 2023

Gestational trophoblastic disease (abbreviated GTD), also gestational trophoblastic neoplasia (abbreviated GTN), 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. (WC)

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

Hydropic abortus

General

  • May be seen in the context of a previously detected fetal heart beat.

Microsopic

Features:

  • Enlarged chorionic villi with some cisterns.

DDx:[9]

  • Molar pregnancy.

Sign out

Submitted as "Retained Products of Conception":
- Small and large chorionic villi with cisterns, suggestive of hydropic abortus, see comment.
- Benign decidual tissue present.
- Negative for evidence of fetal tissue in sampled tissue, see comment.
 
Comment:
Imaging previously described a gestational sac and a fetal heart beat.

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.
  • "Norwegian fjord periphery"[5] - 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.
Main article: Placental site nodule

Exaggerated placental site

  • Abbreviated EPS.
  • Previously known as syncytial endometritis.[16]
Main article: Exaggerated placental site

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[17] with granular IgM staining.[18]

Clinical:

  • Raised (serum) beta-hCG - but usually not has high as in choriocarcinoma.
    • In ~70% < 1000 IU/L.[19]
    • In a series of 55 cases the average beta-hCG was ~700 IU/L.[20]
  • Prognosis dependent on time of diagnosis from last pregnancy.
    • <48 months = good prognosis.[19]

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:[22]

  • 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:[23]

  • Solid mass.
  • Flesh-like appearance.

Image:

Microscopic

Features:[24]

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

DDx:

Images:

IHC

Features:[25]

  • 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. ↑ 5.0 5.1 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.
  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. ↑ Rios-Doria E, Pennington KP, Reiter DJ, Parker EU (September 2023). "Diagnostic challenges in differentiating between hydropic abortus, and complete and partial hydatidiform molar pregnancies in early gestation". Int J Gynecol Cancer 33 (9): 1482–1484. doi:10.1136/ijgc-2022-004104. PMID 37268312.
  10. ↑ URL: http://pathologyoutlines.com/placenta.html#incompletemole. Accessed on: 9 August 2011.
  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. ↑ URL: http://www.webpathology.com/image.asp?case=565&n=7. Accessed on: 22 May 2014.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 19.0 19.1 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.
  20. ↑ 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.
  21. ↑ URL: http://www.webpathology.com/image.asp?n=3&Case=588. Accessed on: 1 January 2012.
  22. ↑ 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.
  23. ↑ 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.
  24. ↑ 24.0 24.1 URL: http://www.webpathology.com/image.asp?case=589&n=2. Accessed on: 15 August 2011.
  25. ↑ 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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