Difference between revisions of "Gestational trophoblastic disease"

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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=
===Most common===
===Most common===
Overview of gestational trophoblastic disease:
Overview of gestational trophoblastic disease:
{| class="wikitable"
{| class="wikitable sortable"
|
! Type of mole
| '''Gross'''
! Gross
| '''Nuclear atypia'''
! [[Nuclear atypia]]
| '''Villi'''
! [[Chorionic villi]]
| '''[[IHC]]'''
! [[IHC]]
| '''DNA content'''
! DNA content
| '''Images'''
! Micrographs
|-
|-
| Complete mole
| Complete mole
| "snowstorm"
| "snowstorm"
| +/- ?
| +/- ?
| yes, all abnormal <ref>[http://pathologyoutlines.com/placenta.html#completemole http://pathologyoutlines.com/placenta.html#completemole]</ref>
| yes, all abnormal  
| p57(KIP2) -ve
| p57(KIP2) -ve
| Paternal, diploid
| Paternal, diploid
| [http://www.pathconsultddx.com/pathCon/largeImage?pii=S1559-8675%2806%2970167-X&figureId=fig1 Complete mole (pathconsultddx.com)]
| [http://commons.wikimedia.org/wiki/File:Intermediate_trophoblast_3_-_low_mag.jpg complete mole + intermed. trophoblast (WC)], [http://en.wikipedia.org/wiki/File:Hydatidiform_mole_%281%29_complete_type.jpg complete mole (WC)]  
|-
|-
| Partial mole
| Partial mole
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| p57(KIP2) +ve
| p57(KIP2) +ve
| Maternal & paternal, tripoid
| Maternal & paternal, tripoid
| [http://library.med.utah.edu/WebPath/PLACHTML/PLAC064.html Partial mole (utah.edu)]
| [http://library.med.utah.edu/WebPath/PLACHTML/PLAC064.html partial mole (utah.edu)]
|-
|-
| Choriocarcinoma
| Choriocarcinoma
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| beta-hCG +ve
| beta-hCG +ve
| ?
| ?
| [http://www.webpathology.com/image.asp?case=36&n=1 Choriocarcinoma - testicular (webpathology.com)]
| [[Image:Choriocarcinoma_-2-_very_high_mag.jpg|thumb|center|120px|Choriocarcinoma. (WC)]]
|-
|-
|}
|}
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=Entities=
=Entities=
==Choriocarcinoma==
==Choriocarcinoma==
===General===
{{Main|Choriocarcinoma}}
*Classified as a [[germ cell tumour]].
*Usually a mixed tumour, i.e. pure choriocarcinoma is rare, e.g. [[dysgerminoma]] + choriocarcinoma.
 
===Clinical/Epidemiology===
*High beta-hCG.
*May be preceded by a complete hydatidiform mole.<ref name=Ref_PBoD1110-1>{{Ref PBoD|1110-1111}}</ref>
*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:
*[http://www.webpathology.com/image.asp?case=36&n=1 Choriocarcinoma (webpathology.com)].
*[http://oac.med.jhmi.edu/Pathology/Repro/Placenta/279B_Full.html Choriocarcinoma - testicular (med.jhmi.edu)].
 
Notes:
*Its usually ''NOT'' choriocarcinoma if there are villi.<ref>Notebook P.180. 21 September 2009.</ref>
 
===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>


==Hydatidiform moles==
==Hydatidiform moles==
Line 90: Line 66:


====Types====
====Types====
*Partial mole - see [[partial mole]].
#Partial mole - see [[partial mole]].
*Complete mole - see [[complete mole]].
#Complete mole - see [[complete mole]].
 
Extent:
*Invasive mole - '''not''' a subtype.
**Within uterine muscle +/- vessels.


===Microscopic===
===Microscopic===
Hydropic changes:
Hydropic changes:
{| class="wikitable"
{| class="wikitable sortable"
| '''Entity'''
! Entity
| '''Villi (outline)'''
! [[Chorionic villi]] (outline)
| '''Cisterns'''
! Cisterns
| '''Blood vessels'''
! [[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
| '''Image'''
! Micrograph
|-
|-
| Complete mole
| Complete mole
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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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===IHC===
===IHC===
*p57(KIP2) - the gene is strongly paternally imprinted and the paternal copy is inactived; its expression is from the maternal gene.
*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.<ref name=pmid15754295>{{cite journal |author=Merchant SH, Amin MB, Viswanatha DS, Malhotra RK, Moehlenkamp C, Joste NE |title=p57KIP2 immunohistochemistry in early molar pregnancies: emphasis on its complementary role in the differential diagnosis of hydropic abortuses |journal=Hum. Pathol. |volume=36 |issue=2 |pages=180–6 |year=2005 |month=February |pmid=15754295 |doi=10.1016/j.humpath.2004.12.007 |url=}}</ref>
**Complete moles lack the maternal genome; thus, p57(KIP2) immunostaining (in the cytotrophoblasts and villous stromal cells) is absent.<ref name=pmid15754295>{{cite journal |author=Merchant SH, Amin MB, Viswanatha DS, Malhotra RK, Moehlenkamp C, Joste NE |title=p57KIP2 immunohistochemistry in early molar pregnancies: emphasis on its complementary role in the differential diagnosis of hydropic abortuses |journal=Hum. Pathol. |volume=36 |issue=2 |pages=180–6 |year=2005 |month=February |pmid=15754295 |doi=10.1016/j.humpath.2004.12.007 |url=}}</ref><ref name=pmid12514787>{{Cite journal  | last1 = Fukunaga | first1 = M. | title = Immunohistochemical characterization of p57(KIP2) expression in early hydatidiform moles. | journal = Hum Pathol | volume = 33 | issue = 12 | pages = 1188-92 | month = Dec | year = 2002 | doi = 10.1053/hupa.2002.129421 | PMID = 12514787 }}</ref>
***Intermediate trophoblasts and maternal tissue are positive controls.<ref name=pmid12514787/>  
**Memory device:  
**Memory device:  
***'''''p'''57 is '''p'''ositive in '''p'''artial moles''.
***'''''p'''57 is '''p'''ositive in '''p'''artial moles''.
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*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>


==Partial Mole==
==Hydropic abortus==
*Formal name: ''partial hydatidiform mole''.
===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==
*[[AKA]] ''partial mole''.


===General===
===General===
Genetics:
Genetics:
*Polypoid - usually triploid (e.g. 69XXY).
*Usually triploid (e.g. 69XXY).
Images: [http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=12&cat2=86&cat3=795&cat4=3&stype=n]


===Microscopic===
===Microscopic===
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***Contain fluid in the centre, i.e. are "hydropic".
***Contain fluid in the centre, i.e. are "hydropic".
**Villi with cytotrophoblastic inclusions.
**Villi with cytotrophoblastic inclusions.
***Cytotrophoblast in the core of a villus (normally it is only at the surface of the villus).
***[[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.
*May have fetal parts, such as nucleated RBCs.
*Trophoblastic proliferation.
*Trophoblastic proliferation.
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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:  
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*[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)].


==Complete Mole==
===IHC===
*Formal name: ''complete hydatidiform mole''.
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>
*Also known as ''classic mole''.
*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===
===General===
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*Male derived, i.e. arise from DNA in sperm; empty egg fertilized.  
*Male derived, i.e. arise from DNA in sperm; empty egg fertilized.  


===Radiology===
===Gross/Radiology===
*"Snowstorm" appearance on ultrasound.<ref>URL:[http://www.jultrasoundmed.org/cgi/content/abstract/18/9/589 http://www.jultrasoundmed.org/cgi/content/abstract/18/9/589]. Accessed on: 27 July 2010.</ref>
*"Snowstorm" appearance on ultrasound.<ref>URL:[http://www.jultrasoundmed.org/cgi/content/abstract/18/9/589 http://www.jultrasoundmed.org/cgi/content/abstract/18/9/589]. Accessed on: 27 July 2010.</ref>
*May be described as "grape-like" on gross exam.<ref name=pmid18162339>{{Cite journal  | last1 = Abike | first1 = F. | last2 = Temizkan | first2 = O. | last3 = Payasli | first3 = A. | last4 = Avsar | first4 = F. | last5 = Karahan | first5 = N. | last6 = Baspinar | first6 = S. | title = Postmenopausal complete hydatidiform mole: a case report. | journal = Maturitas | volume = 59 | issue = 1 | pages = 95-8 | month = Jan | year = 2008 | doi = 10.1016/j.maturitas.2007.10.005 | PMID = 18162339 }}</ref>
Image:
*[http://library.med.utah.edu/WebPath/PLACHTML/PLAC063.html Complete mole (utah.edu)].


===Microscopic===
===Microscopic===
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**Very rarely nucleated [[RBC]]s.
**Very rarely nucleated [[RBC]]s.


Image:  
====Images====
*[http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70167-X Complete mole (pathconsultddx.com)].
<gallery>
Image:Intermediate_trophoblast_3_-_low_mag.jpg | Complete mole and intermediate trophoblast - intermed. 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==
*[[AKA]] ''invasive mole''.
*[[AKA]] ''chorioadenoma destruens''.<ref name=pmid6300738>{{Cite journal  | last1 = McDonald | first1 = TW. | last2 = Ruffolo | first2 = EH. | title = Modern management of gestational trophoblastic disease. | journal = Obstet Gynecol Surv | volume = 38 | issue = 2 | pages = 67-83 | month = Feb | year = 1983 | doi =  | PMID = 6300738 }}</ref>
===General===
*This is not a distinct subtype - see ''[[hydatidiform mole]]''.
 
===Microscopic===
Features:
*[[Chorionic villi]] - abnormal +/- normal.
*Trophoblastic cells within uterine muscle +/- vessels - '''key feature'''.
 
DDx:
*[[Choriocarcinoma]] - lack [[chorionic villi]], usu. hemorrhagic.
 
====Images====
<gallery>
Image:Invasive hydatidiform mole - very low mag.jpg | Invasive mole - very low 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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! Image
! Image
|-
|-
| [[Placental site nodule]]
| [[Placental site nodule]] (PSN)
| paucicellular, hyaline material
| paucicellular, hyaline material
| no mitotic activity
| no mitotic activity
| IHC?
| p16 -ve, MIB1 low
| [[EPS]] ???
| [[EPS]], [[squamous carcinoma]]
| post-partum
| post-partum
| [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]]
| [[Exaggerated placental site]] (EPS)
| abundant [[intermediate trophoblast]]s - between muscle
| abundant [[intermediate trophoblast]]s - between muscle
| no mitotic activity
| no mitotic activity
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| Image?
| Image?
|-
|-
| Placental site trophoblastic tumour
| [[Placental site trophoblastic tumour]] (PSTT)
| abundant cytoplasm - not clear
| abundant cytoplasm - not clear, dyscohesive
| +/-multinucleation
| +/-multinucleation
| MIB1 high
| MIB1 high, p63 -ve, CD146 +ve
| [[EPS]]
| [[EPS]], [[choriocarcinoma]]
| Other?
| Other?
| [http://www.webpathology.com/case.asp?case=588 (webpathology.com)]
| [http://www.webpathology.com/case.asp?case=588 (webpathology.com)]
|-
|-
| [[Epithelioid trophoblastic tumour]]
| [[Epithelioid trophoblastic tumour]] (ETT)
| nests of cells in hyaline stroma
| nests of cells in hyaline stroma
| eosinophilic cytoplasm, central nucleus
| eosinophilic cytoplasm, central nucleus
| p16-, MIB1 low
| MIB1 low, p63 +ve, CD146 -ve
| [[squamous carcinoma]]
| [[squamous carcinoma]]
| Other?
| Other?
Line 245: Line 291:
|-
|-
| [[Choriocarcinoma]]
| [[Choriocarcinoma]]
| polygonal cells with clear cytoplasm (cytotrophoblasts)
| polygonal cells with clear cytoplasm ([[cytotrophoblast]]s)
| multinucleated cells with smudged nuclei (syncytiotrophoblasts), no [[chorionic villi]]
| multinucleated cells with smudged nuclei ([[syncytiotrophoblast]]s), '''no''' [[chorionic villi]]
| beta-hCG
| beta-hCG +ve, p63 +ve
| DDx?
| [[invasive hydatidiform mole]], [[PSTT]]
| elevated beta-hCG (serum)
| elevated beta-hCG (serum); '''not''' intermediate trophoblast derived.
| [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?
Line 263: Line 309:
==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>
 
===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:
*[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 [[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.


==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.
 
DDx:
*[[PSTT]].
 
===IHC===
*MIB1 ~0%.
**Used to differentiate from [[PSTT]].


==Placental site trophoblastic tumour==
==Placental site trophoblastic tumour==
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*Malignant counterpart of ''exaggerated placental site'' (abbreviated ''EPS'').
*Malignant counterpart of ''exaggerated placental site'' (abbreviated ''EPS'').
===General===
===General===
====Clinical====
*Derived from ''intermediate trophoblast''.
*Raised beta-hCG - but usually not has high as in choriocarcinoma.<ref name=pstt_pc>URL: [http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70463-6 http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70463-6]. Accessed on: 23 September 2009.</ref>
*Follows pregnancy.
*Derived from ''trophoblast'' - the stuff that forms the chorionic villi - remember: ''syncytiotrophoblasts'' (outer layer) and ''cytotrophoblasts'' (inner layer).
*May be associated with [[nephrotic syndrome]]<ref name=pmid15457847>{{Cite journal  | last1 = Bonazzi | first1 = C. | last2 = Urso | first2 = M. | last3 = Dell'Anna | first3 = T. | last4 = Sacco | first4 = S. | last5 = Buda | first5 = A. | last6 = Cantú | first6 = MG. | title = Placental site trophoblastic tumor: an overview. | journal = J Reprod Med | volume = 49 | issue = 8 | pages = 585-8 | month = Aug | year = 2004 | doi =  | PMID = 15457847 }}</ref> with granular IgM staining.<ref>{{Cite journal  | last1 = Komatsuda | first1 = A. | last2 = Nakamoto | first2 = Y. | last3 = Asakura | first3 = K. | last4 = Yasuda | first4 = T. | last5 = Imai | first5 = H. | last6 = Miura | first6 = AB. | title = Case report: nephrotic syndrome associated with a total hydatidiform mole. | journal = Am J Med Sci | volume = 303 | issue = 5 | pages = 309-12 | month = May | year = 1992 | doi =  | PMID = 1580319 }}</ref>


====Epidemiology====
Clinical:
*Usually follows a normal pregnancy ~ 75% of cases.<ref name=pstt_pc>URL: [http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70463-6 http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675(06)70463-6]. Accessed on: 23 September 2009.</ref>
*Raised (serum) beta-hCG - but usually not has high as in [[choriocarcinoma]].
**In ~70% < 1000 IU/L.<ref name=pmid19552948>{{Cite journal  | last1 = Schmid | first1 = P. | last2 = Nagai | first2 = Y. | last3 = Agarwal | first3 = R. | last4 = Hancock | first4 = B. | last5 = Savage | first5 = PM. | last6 = Sebire | first6 = NJ. | last7 = Lindsay | first7 = I. | last8 = Wells | first8 = M. | last9 = Fisher | first9 = RA. | title = Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study. | journal = Lancet | volume = 374 | issue = 9683 | pages = 48-55 | month = Jul | year = 2009 | doi = 10.1016/S0140-6736(09)60618-8 | PMID = 19552948 }}</ref>
**In a series of 55 cases the average beta-hCG was ~700 IU/L.<ref name=pmid16246400>{{Cite journal  | last1 = Baergen | first1 = RN. | last2 = Rutgers | first2 = JL. | last3 = Young | first3 = RH. | last4 = Osann | first4 = K. | last5 = Scully | first5 = RE. | title = Placental site trophoblastic tumor: A study of 55 cases and review of the literature emphasizing factors of prognostic significance. | journal = Gynecol Oncol | volume = 100 | issue = 3 | pages = 511-20 | month = Mar | year = 2006 | doi = 10.1016/j.ygyno.2005.08.058 | PMID = 16246400 }}</ref>
*Prognosis dependent on time of diagnosis from last pregnancy.
**<48 months = good prognosis.<ref name=pmid19552948/>


===Microscopic===
===Microscopic===
Features:
Features:
*Large cells.
*Large cells:
*Nuclear pleomorphism.
**Nuclear pleomorphism.
*Cytoplasm:
**Cytoplasm:
**Abundant.  
***Abundant.  
**Solid, i.e. not vesicular.
***Solid, i.e. not vesicular.
**Light basophilic, not clear - '''key feature'''.
***Light basophilic, not clear - '''key feature'''.
*NC ratio ~ normal.
**[[NC ratio]] ~ normal.
*+/-Multinucleated cells.
*+/-Multinucleated cells.
*Ectatic blood vessels.
Note:
*'''No''' chorionic villi.
**If villi are present... it is probably a [[hydatidiform mole]].


DDx:
DDx:
*[[Exaggerated placental site]].
*[[Exaggerated placental site]] - EPS has near zero Ki-67.
*[[Choriocarcinoma]].
*[[Choriocarcinoma]] - choriocarcinoma biphasic.<ref>URL: [http://www.webpathology.com/image.asp?n=3&Case=588 http://www.webpathology.com/image.asp?n=3&Case=588]. Accessed on: 1 January 2012.</ref>
 
EPS vs. PSTT:
*EPS has a low MIB1 (Ki-67).


Images:
Images:
*[http://www.webpathology.com/case.asp?case=588 Collection of PSTT images (webpathology.com)].
*[http://www.webpathology.com/case.asp?case=588 Collection of PSTT images (webpathology.com)].
===IHC===
Features:<ref>{{Cite journal  | last1 = Shih | first1 = IM. | last2 = Kurman | first2 = RJ. | title = 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. | journal = Hum Pathol | volume = 29 | issue = 1 | pages = 27-33 | month = Jan | year = 1998 | doi =  | PMID = 9445130 }}</ref>
*CD146 +ve.
*p63 -ve.
*Ki-67 ~14+/-7%.
**Choriocarcinoma ~69+/-20%.


==Epithelioid trophoblastic tumour==
==Epithelioid 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===
Line 370: Line 388:
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===
Features:<ref name=pmid16931955>{{Cite journal  | last1 = Mao | first1 = TL. | last2 = Seidman | first2 = JD. | last3 = Kurman | first3 = RJ. | last4 = Shih | first4 = IeM. | title = Cyclin E and p16 immunoreactivity in epithelioid trophoblastic tumor--an aid in differential diagnosis. | journal = Am J Surg Pathol | volume = 30 | issue = 9 | pages = 1105-10 | month = Sep | year = 2006 | doi = 10.1097/01.pas.0000209854.28282.87 | PMID = 16931955 }}</ref>
*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=
=See also=
Line 383: Line 413:


[[Category:Gynecologic pathology]]
[[Category:Gynecologic pathology]]
[[Category:Gestational trophoblastic disease]]
Michael
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