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Gestational trophoblastic disease (view source)

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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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==Choriocarcinoma==
==Choriocarcinoma==
{{Main|Choriocarcinoma}}
{{Main|Choriocarcinoma}}
===General===
*Classified as a [[germ cell tumour]].
*May be preceded by a [[complete hydatidiform mole]].<ref name=Ref_PBoD1110-1>{{Ref PBoD|1110-1111}}</ref>
===Gross===
*Dark, shaggy, focally hemorrhagic & friable/necrotic-appearing.
*Invasive border.
===Microscopic===
Features:
*Two cell populations:
#'''C'''ytotrophoblasts - '''key feature'''.
#*'''C'''lear cytoplasm.
#*Polygonal shaped cells in cords/masses.
#*Distinct cell borders.
#*Single uniform nucleus.
#Syncytiotrophoblasts - may be absent.<ref>URL: [http://www.webpathology.com/image.asp?n=4&Case=36 http://www.webpathology.com/image.asp?n=4&Case=36]. Accessed on: 8 February 2011.</ref>
#*Large + many irreg. or lobular hyperchromatic nuclei.
#*Eosinophilic vacuolated cytoplasm (contains hCG).
*+/-Hemorrhage.
*+/-Necrosis.
Notes:
*No ''[[chorionic villi]]'' should be present.
**If chorionic villi are present... it is likely a type of [[hydatidiform mole]].
*The dual cell population may not be evident at first.
**Hemorrhage and marked nuclear pleomorphism are suggestive of the diagnosis.
Images:
*www:
**[http://www.webpathology.com/image.asp?n=5&Case=36 Choriocarcinoma - low mag. (webpathology.com)].
**[http://www.webpathology.com/image.asp?case=36&n=1 Choriocarcinoma (webpathology.com)].
**[http://www.webpathology.com/image.asp?n=4&Case=36 Choriocarcinoma (webpathology.com)].
**[http://chestjournal.chestpubs.org/content/138/1/220.full Choriocarcinoma (chestjournal.chestpubs.org)].<ref>{{Cite journal  | last1 = Venkatram | first1 = S. | last2 = Muppuri | first2 = S. | last3 = Niazi | first3 = M. | last4 = Fuentes | first4 = GD. | title = A 24-year-old pregnant patient with diffuse alveolar hemorrhage. | journal = Chest | volume = 138 | issue = 1 | pages = 220-3 | month = Jul | year = 2010 | doi = 10.1378/chest.09-2688 | PMID = 20605823 }}</ref>
**[http://oac.med.jhmi.edu/Pathology/Repro/Placenta/279B_Full.html Choriocarcinoma - uterus (med.jhmi.edu)].
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Choriocarcinoma_-2-_high_mag.jpg Choriocarcinoma - high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Choriocarcinoma_-2-_very_high_mag.jpg Choriocarcinoma - very high mag. (WC)].
===IHC===
*beta-hCG +ve.<ref name=pmid19145204>{{cite journal |author=Kalhor N, Ramirez PT, Deavers MT, Malpica A, Silva EG |title=Immunohistochemical studies of trophoblastic tumors |journal=Am. J. Surg. Pathol. |volume=33 |issue=4 |pages=633–8 |year=2009 |month=April |pmid=19145204 |doi=10.1097/PAS.0b013e318191f2eb |url=}}</ref>
**Classically said to be produced by syncytiotrophoblasts.<ref name=pmid20735820>{{Cite journal  | last1 = Cole | first1 = LA. | title = Biological functions of hCG and hCG-related molecules. | journal = Reprod Biol Endocrinol | volume = 8 | issue =  | pages = 102 | month =  | year = 2010 | doi = 10.1186/1477-7827-8-102 | PMID = 20735820 | PMC = 2936313 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936313/ }}
</ref>
***[[Cytotrophoblast]]s also produce some.<ref name=pmid20735820/><ref name=pmid12242037>{{Cite journal  | last1 = Kovalevskaya | first1 = G. | last2 = Genbacev | first2 = O. | last3 = Fisher | first3 = SJ. | last4 = Caceres | first4 = E. | last5 = O'Connor | first5 = JF. | title = Trophoblast origin of hCG isoforms: cytotrophoblasts are the primary source of choriocarcinoma-like hCG. | journal = Mol Cell Endocrinol | volume = 194 | issue = 1-2 | pages = 147-55 | month = Aug | year = 2002 | doi =  | PMID = 12242037 }}</ref>


==Hydatidiform moles==
==Hydatidiform moles==
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! [[Blood vessel]]s
! [[Blood vessel]]s
! Nucleated RBCs
! Nucleated RBCs
! p57 / Ki-67<ref>URL: [http://www.ihcworld.com/_newsletter/2003/focus_mar_2003.pdf http://www.ihcworld.com/_newsletter/2003/focus_mar_2003.pdf]. Accessed on: 28 May 2011.</ref> staining
! p57 / Ki-67<ref>URL: [http://www.ihcworld.com/_newsletter/2003/focus_mar_2003.pdf http://www.ihcworld.com/_newsletter/2003/focus_mar_2003.pdf]. Accessed on: 28 May 2011.</ref> staining ‡
! Ploidy
! Ploidy
! Micrograph
! Micrograph
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| [http://www.ipath-network.com/ipath/object/view/181344]
| [http://www.ipath-network.com/ipath/object/view/181344]
|}
|}
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.


====Mole vs. normal====
====Mole versus normal====
*Moles have large [[chorionic villi]] with edema and abnormal blood vessels.<ref>URL: [http://pathologyoutlines.com/placenta.html#hydatgeneral http://pathologyoutlines.com/placenta.html#hydatgeneral].</ref>
*Moles have large [[chorionic villi]] with edema and abnormal blood vessels.<ref>URL: [http://pathologyoutlines.com/placenta.html#hydatgeneral http://pathologyoutlines.com/placenta.html#hydatgeneral].</ref>


====Non-molar vs. partial vs. complete - short version====
====Non-molar versus partial versus complete - short version====
Features:<ref>{{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.
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===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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*"Norwegian fjord periphery"<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> - jagged border / irregular sawtooth-like periphery.
*"Norwegian fjord periphery"<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> - jagged border / irregular sawtooth-like periphery.
**Complete moles tend to have a smooth border
**Complete moles tend to have a smooth border
DDx:
*[[Complete hydatidiform mole]].
*[[Placental mesenchymal dysplasia]].
*Hydropic abortus - see [[products of conception]] and [[chorionic villi]].


Images:  
Images:  
*[http://www-medlib.med.utah.edu/WebPath/PLACHTML/PLAC067.html Partial mole (med.utah.edu)].
*[http://www-medlib.med.utah.edu/WebPath/PLACHTML/PLAC067.html Partial mole (med.utah.edu)].
*[http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=12&cat2=86&cat3=795&cat4=3&stype=n Partial mole - several images (gfmer.ch)].
*[http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=12&cat2=86&cat3=795&cat4=3&stype=n Partial mole - several images (gfmer.ch)].
===IHC===
Features:<ref name=pmid22218717>{{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>
*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==
==Complete hydatidiform mole==
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**Very rarely nucleated [[RBC]]s.
**Very rarely nucleated [[RBC]]s.


Images:
====Images====
*[http://commons.wikimedia.org/wiki/File:Intermediate_trophoblast_3_-_low_mag.jpg Complete mole and intermediate trophoblast - intermed. mag. (WC)].
<gallery>
*[http://commons.wikimedia.org/wiki/File:Hydatidiform_mole_%281%29_complete_type.jpg Complete mole - low mag. (WC)].
Image:Intermediate_trophoblast_3_-_low_mag.jpg | Complete mole and intermediate trophoblast - intermed. mag. (WC)
*[http://commons.wikimedia.org/wiki/File:Hydatidiform_mole_%282%29_complete_type.jpg Complete mole - high mag. (WC)].
Image:Hydatidiform_mole_%281%29_complete_type.jpg | Complete mole - low mag. (WC)
Image:Hydatidiform_mole_%282%29_complete_type.jpg | Complete mole - high mag. (WC)
</gallery>


==Invasive hydatidiform mole==
==Invasive hydatidiform mole==
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*[[Choriocarcinoma]] - lack [[chorionic villi]], usu. hemorrhagic.
*[[Choriocarcinoma]] - lack [[chorionic villi]], usu. hemorrhagic.


Images:
====Images====
*[http://commons.wikimedia.org/wiki/File:Invasive_hydatidiform_mole_-_low_mag.jpg Invasive mole - low mag. (WC)].
<gallery>
*[http://commons.wikimedia.org/wiki/File:Invasive_hydatidiform_mole_-_intermed_mag.jpg Invasive mole - intermed. mag. (WC)].
Image:Invasive hydatidiform mole - very low mag.jpg | Invasive mole - very low mag. (WC)
*[http://commons.wikimedia.org/wiki/File:Invasive_hydatidiform_mole_-_high_mag.jpg Invasive mole - high mag. (WC)].
Image:Invasive_hydatidiform_mole_-_low_mag.jpg | Invasive mole - low mag. (WC)
Image:Invasive_hydatidiform_mole_-_intermed_mag.jpg | Invasive mole - intermed. mag. (WC)
Image:Invasive_hydatidiform_mole_-_high_mag.jpg | Invasive mole - high mag. (WC)
Image:Invasive hydatidiform mole - very high mag.jpg | Invasive mole - very high mag. (WC)
</gallery>


=Entities - intermediate trophoblast=
=Entities - intermediate trophoblast=
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| [[EPS]], [[squamous carcinoma]]
| [[EPS]], [[squamous carcinoma]]
| post-partum
| post-partum
| [http://commons.wikimedia.org/wiki/File:Placental_site_nodule_-_intermed_mag.jpg (WC)], [http://www.ijpmonline.org/viewimage.asp?img=IndianJPatholMicrobiol_2009_52_2_240_48931_u4.jpg (ijpmonline.org)]
| [[Image:Placental_site_nodule_-_intermed_mag.jpg |thumb| center| 80px|PSN. (WC)]] [http://www.ijpmonline.org/viewimage.asp?img=IndianJPatholMicrobiol_2009_52_2_240_48931_u4.jpg (ijpmonline.org)]
|-
|-
| [[Exaggerated placental site]] (EPS)
| [[Exaggerated placental site]] (EPS)
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| [[invasive hydatidiform mole]], [[PSTT]]
| [[invasive hydatidiform mole]], [[PSTT]]
| elevated beta-hCG (serum); '''not''' intermediate trophoblast derived.
| elevated beta-hCG (serum); '''not''' intermediate trophoblast derived.
| [http://commons.wikimedia.org/wiki/File:Choriocarcinoma_-2-_very_high_mag.jpg (WC)], [http://www.webpathology.com/image.asp?case=36&n=1 (webpathology.com)]
| [[Image:Choriocarcinoma_-2-_very_high_mag.jpg|thumb|center|120px|Choriocarcinoma. (WC)]] [http://www.webpathology.com/image.asp?case=36&n=1 (webpathology.com)]
|- <!--
|- <!--
| Entity?
| Entity?
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==Placental site nodule==
==Placental site nodule==
*Abbreviated ''PSN''.
*Abbreviated ''PSN''.
 
{{Main|Placental site nodule}}
===General===
*Benign.
*Intermediate trophoblast remnants from a previous gestation.<ref name=pmid19332926>{{Cite journal  | last1 = Jacob | first1 = S. | last2 = Mohapatra | first2 = D. | title = Placental site nodule: a tumor-like trophoblastic lesion. | journal = Indian J Pathol Microbiol | volume = 52 | issue = 2 | pages = 240-1 | month =  | year =  | doi =  | PMID = 19332926 | url = http://www.ijpmonline.org/text.asp?2009/52/2/240/48931 }}</ref>
*Usually an incidental finding.
 
Clinical:
*Usually asymptomatic.
*Vaginal bleeding. (?)
*Infertility. (?)
 
===Microscopic===
Features:<ref name=pmid19332926/>
*Paucicellular with hyaline material scattered cells.
*Variable cell population:
**Small-large cells.
**Clear to eosinophilic cytoplasm.
**+/-Multinucleation.
 
Notes:
*No mitotic activity.
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Placental_site_nodule_-_intermed_mag.jpg PSN - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Placental_site_nodule_-_high_mag.jpg PSN - high mag. (WC)].
*www:
**[http://www.ijpmonline.org/viewimage.asp?img=IndianJPatholMicrobiol_2009_52_2_240_48931_u4.jpg PSN (ijpmonline.org)].<ref name=pmid19332926/>
**[http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=12&cat3=1256&stype=d PSN (gfmer.ch)] - includes images from ''Jacob and Mohapatra''.<ref name=pmid19332926/>
 
DDx:
*Invasive (cervical) [[squamous cell carcinoma]].
**Can be sorted-out with IHC (SCC will typically be: p16 +ve, MIB1 +ve).
*[[Exaggerated placental site]].
**Different histomorphology than PSN; EPS:<ref name=pmid19332926/> syncytiotrophoblastic tissue, in cords/nests, no hyaline nodules.
 
===IHC===
Features:<ref name=pmid19332926/>
*Inhibin alpha +ve.
*CK18 +ve.
*MIB1 low.
 
Other:
*p16 -ve.


==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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*Vaginal bleeding.  
*Vaginal bleeding.  
*Elevated beta-hCG.
*Elevated beta-hCG.
===Gross===
Features:<ref name=pmid16258513>{{Cite journal  | last1 = Fadare | first1 = O. | last2 = Parkash | first2 = V. | last3 = Carcangiu | first3 = ML. | last4 = Hui | first4 = P. | title = Epithelioid trophoblastic tumor: clinicopathological features with an emphasis on uterine cervical involvement. | journal = Mod Pathol | volume = 19 | issue = 1 | pages = 75-82 | month = Jan | year = 2006 | doi = 10.1038/modpathol.3800485 | PMID = 16258513 }}</ref>
*Solid mass.
*Flesh-like appearance.
Image:


===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]]
Michael
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