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[[Image:Mixed_Germ_Cell_Tumor_of_Testis_(3260625567).jpg|thumb|right|Testicular [[mixed germ cell tumour]]. (WC/euthman)]]
This article covers '''germ cell tumours''', often abbreviated [[GCT]], which classically arise in the gonads ([[ovary]], [[testis]]).  They are also found in the midline and make appearances in [[neuropathology]] (e.g. [[pineal gland]]) and in the [[mediastinum]].
This article covers '''germ cell tumours''', often abbreviated [[GCT]], which classically arise in the gonads ([[ovary]], [[testis]]).  They are also found in the midline and make appearances in [[neuropathology]] (e.g. [[pineal gland]]) and in the [[mediastinum]].


==Overview==
==Overview==
===Germ cell tumour - types===
Precusor:
Precusor:
*[[Intratubular germ cell neoplasia]].
*[[Intratubular germ cell neoplasia]].
Line 18: Line 20:
*[[Gonadoblastoma]].
*[[Gonadoblastoma]].
*[[Polyembryoma]].
*[[Polyembryoma]].
===Grossing===
{{Main|Orchiectomy}}
*1 cm<sup>2</sup> of tumour per cm of maximal tumour dimension - guideline for testicular cancer.<ref>URL: [http://www.uroweb.org/gls/pdf/10_Testicular_Cancer.pdf http://www.uroweb.org/gls/pdf/10_Testicular_Cancer.pdf]. Accessed on: 30 October 2012.</ref>


===IHC for GCTs===
===IHC for GCTs===
ABCDs of GCTs:
====ISUP====
An algorithmic approach based on the ISUP consensus paper by Ulbright ''et al.'':<ref name=pmid24832161>{{cite journal |author=Ulbright TM, Tickoo SK, Berney DM, Srigley JR |title=Best practices recommendations in the application of immunohistochemistry in testicular tumors: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=e50–9 |year=2014 |month=August |pmid=24832161 |doi=10.1097/PAS.0000000000000233 |url=}}</ref>
{{familytree/start}}
{{familytree | | | | | | | | | | | | | A01 | | | | | | | | | | | | | | | | | | |A01=[[Germ cell tumours]]}}
{{familytree | | | | | |,|-|-|-|-|-|-|-|^|-|-|-|-|-|-|-|.| | | | | | | | | | | |}}
{{familytree | | | | | B01 | | | | | | | | | | | | | | B02 | | | | | | | | | | |B01=OCT4 +ve | B02=OCT4 -ve}}
{{familytree | |,|-|-|-|^|-|-|-|.| | | | | |,|-|-|-|-|-|+|-|-|-|-|-|.| | | | | |}}
{{familytree | C01 | | | | | | C02 | | | | C03 | | | | C04 | | | | C05 | | | | |C01=CD117 +ve<br>CD30 -ve |C02= CD117 -ve<br>CD30 +ve|C03=[[Glypican 3]] +ve<br>AFP +ve<br>beta-hCG -ve|C04=Glypican 3 ?<br>AFP -ve<br>beta-hCG +ve|C05=Glypican 3 -ve<br>AFP -ve<br>beta-hCG -ve}}
{{familytree | |!| | | | | | | |!| | | | | |!| | | | | |!| | | | | |!| | | | | |}}
{{familytree | D01 | | | | | | D02 | | | | D03 | | | | D04 | | | | D05 | | | | |D01=[[Seminoma]]|D02=[[Embryonal carcinoma]]|D03=[[Yolk sac tumour]]|D04=[[Choriocarcinoma]] |D05= [[Spermatocytic seminoma]] }}
{{familytree/end}}
 
====ABCDs of GCTs====
*AFP - yolk sac tumour.
*AFP - yolk sac tumour.
*Beta-hCG - choriocarcinoma.
*Beta-hCG - choriocarcinoma.
*CD30 - embryonal carcinoma.
*CD30 - embryonal carcinoma.
*D2-40 - seminoma.
*D2-40 - seminoma.
====GCT versus sex cord-stromal tumour====
The ISUP recommends:<ref name=pmid25025364>{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*[[SALL4]] +ve (in GCTs).<ref name=pmid24525512>{{cite journal |author=Miettinen M, Wang Z, McCue PA, ''et al.'' |title=SALL4 expression in germ cell and non-germ cell tumors: a systematic immunohistochemical study of 3215 cases |journal=Am. J. Surg. Pathol. |volume=38 |issue=3 |pages=410–20 |year=2014 |month=March |pmid=24525512 |doi=10.1097/PAS.0000000000000116 |url=}}</ref>
*Alpha-inhibin -ve (+ve in [[SCST]]).
*Calretinin -ve (+ve in SCST).
Alternates for SALL4 are:<ref name=pmid25025364/>
*OCT4 and GPC3.


===Tabular summary of GCTs===
===Tabular summary of GCTs===
{| class="wikitable"
{| class="wikitable sortable"
!| Tumour
! Tumour
!| Key feature
! Key feature
!| Microscopic
! Microscopic
!| IHC
! IHC
!| Other
! Other
!| Image
! Image
|-  
|-  
| Intratubular germ cell neoplasia (ITGCN)
| [[Germ cell neoplasia in situ]] (GCNIS)
| nests of small fried egg cells
| nests of small fried egg cells
| large central nucleus, clear <br>cytoplasm, squared-off nuclear membrane, nucleoli<ref name=Ref_GUP538>{{Ref GUP|538}}</ref>
| large central nucleus, clear <br>cytoplasm, squared-off nuclear membrane, nucleoli<ref name=Ref_GUP538>{{Ref GUP|538}}</ref>
| CD117
| CD117 +ve, CD30 -ve
| appearance similar to seminoma
| appearance similar to [[seminoma]]
| [http://commons.wikimedia.org/wiki/File:Intratubular_germ_cell_neoplasia_high_mag.jpg], [http://commons.wikimedia.org/wiki/File:Intratubular_germ_cell_neoplasia_high_mag_cropped.jpg]
| [[Image:Intratubular_germ_cell_neoplasia_high_mag_cropped.jpg|thumb|center|150px|GCNIS (WC/Nephron)]]
|-  
|-  
| Germinoma / Seminoma / Dysgerminoma
| [[Germinoma]] / [[Seminoma]] / [[Dysgerminoma]]
| fried egg cells
| fried egg cells
| fried egg-like cells (central nucleus, clear <br>cytoplasm) with squared-off nuclear <br>membrane, nucleoli, lymphocytic infiltrate, granulomata,<br>syncytiotrophoblastic giant cells<ref name=Ref_GUP542>{{Ref GUP|542}}</ref>
| fried egg-like cells (central nucleus, clear <br>cytoplasm) with squared-off nuclear <br>membrane, nucleoli, lymphocytic infiltrate, granulomata,<br>syncytiotrophoblastic giant cells<ref name=Ref_GUP542>{{Ref GUP|542}}</ref>
| D2-40
| D2-40
| seminoma = male version of this tumour; dysgerminoma = female version of this tumour
| seminoma = male version of this tumour; dysgerminoma = female version of this tumour
| [http://commons.wikimedia.org/wiki/File:Seminoma_high_mag.jpg], [http://commons.wikimedia.org/wiki/File:Seminoma_intermed_mag.jpg]
| [[Image:Seminoma_intermed_mag.jpg|thumb|center|150px|Seminoma (WC/Nephron)]]
|-  
|-  
| [[Yolk sac tumour]] (endodermal sinus tumour)
| [[Yolk sac tumour]] (endodermal sinus tumour)
| Schiller-Duval bodies
| Schiller-Duval bodies
| Schiller-Duval b. = central blood vessel surrounded by epithelial-like cells a space and more epithelial-like cells, variable arch.  
| Schiller-Duval b. = central blood vessel surrounded by epithelial-like cells a space and more epithelial-like cells, variable arch.  
| AFP
| [[AFP]] +ve, [[Glypican 3]] +ve
| patterns: microcystic, solid, hepatoid
| patterns: microcystic, solid, hepatoid
| [http://webpathology.com/image.asp?case=34&n=6 hepatoid YST]
| [[Image:Mixed_germ_cell_tumour_-_very_high_mag.jpg|thumb|center|150px|Yolk sac tumour (WC)]]
|-  
|-  
| [[Embryonal carcinoma]]
| [[Embryonal carcinoma]]
| prominent nucleoli, vescicular nuclei
| prominent nucleoli, vescicular nuclei
| var. arch.: tubulopapillary, glandular, solid, embryoid bodies (ball of cells in surrounded by empty space on three sides), +/-nuclear overlap, mitoses common
| var. arch.: tubulopapillary, glandular, solid, embryoid bodies (ball of cells in surrounded by empty space on three sides), +/-nuclear overlap, mitoses common
| CD30
| CD30 +ve, CD117 -ve
| usu. part of a mixed GCT  
| usu. part of a mixed GCT  
| [http://commons.wikimedia.org/wiki/File:Embryonal_carcinoma_intermed_mag.jpg], [http://www.webpathology.com/image.asp?case=33&n=1], [http://www.webpathology.com/image.asp?n=4&Case=37]
| [[Image:Embryonal_carcinoma_high_mag.jpg|thumb|center|150px|Embryonal carcinoma (WC/Nephron)]]
|-  
|-  
| [[Choriocarcinoma]]
| [[Choriocarcinoma]]
| clear cytoplasm  
| clear cytoplasm  
| cells with abundant clear cytoplasm and eccentric atypical nuclei (cytotrophoblast), very large (multinucleated) cells with abundant eosinophilic cytoplasm and extreme nuclear atypia (syncytiotrophoblast)
| cells with abundant clear cytoplasm and eccentric atypical nuclei (cytotrophoblast), very large (multinucleated) cells with abundant eosinophilic cytoplasm and extreme nuclear atypia (syncytiotrophoblast)
| beta-hCG
| beta-hCG +ve
| may be preceded by a [[complete mole|complete hydatidiform mole]]
| may be preceded by a [[complete mole|complete hydatidiform mole]]
| [http://www.webpathology.com/image.asp?case=36&n=1], [http://www.webpathology.com/image.asp?n=2&Case=36]
| [[Image:Choriocarcinoma_-2-_very_high_mag.jpg|thumb|center|150px|Choriocarcinoma. (WC/Nephron)]]
|-  
|-  
| [[Teratoma]], immature
| [[Teratoma]], immature
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| pseudostratified epithelium in rosettes (gland-like arrangement)
| pseudostratified epithelium in rosettes (gland-like arrangement)
| None
| None
| teratoma are always malignant in males
| testicular teratomas in post-pubertal males are all considered malignant<ref>{{Cite journal  | last1 = Carver | first1 = BS. | last2 = Al-Ahmadie | first2 = H. | last3 = Sheinfeld | first3 = J. | title = Adult and pediatric testicular teratoma. | journal = Urol Clin North Am | volume = 34 | issue = 2 | pages = 245-51; abstract x | month = May | year = 2007 | doi = 10.1016/j.ucl.2007.02.013 | PMID = 17484929 }}</ref>
| [http://commons.wikimedia.org/wiki/File:Primitive_neuroepithelium_intermed_mag.jpg]
| [[Image:Primitive_neuroepithelium_intermed_mag.jpg|thumb|center|150px|Primitive neuroepithelium (WC/Nephron)]]
|-  
|-  
| [[Mixed germ cell tumour]]
| [[Mixed germ cell tumour]]
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| NA
| NA
| -
| -
| [http://commons.wikimedia.org/wiki/File:Mixed_germ_cell_tumour_-_intermed_mag.jpg]
| [[Image:Mixed_germ_cell_tumour_-_intermed_mag.jpg|thumb|center|150px|Mixed GCT (WC/Nephron)]]
|-  
|-  
| [[Gonadoblastoma]]
| [[Gonadoblastoma]]
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| ?
| ?
| often abnormal karyotype; usu. Y chromosome present
| often abnormal karyotype; usu. Y chromosome present
| [http://commons.wikimedia.org/wiki/File:Gonadoblastoma_-_intermed_mag.jpg]
| [[Image:Gonadoblastoma_-_intermed_mag.jpg|thumb|center|150px|Gonadoblastoma (WC/Nephron)]]
|}
|}


===Molecular pathology===
===Molecular pathology===
Most common cytogenetic abnormality in GCTs:
Most common cytogenetic abnormality in GCTs:
* Isochromosome p12.<ref name=pmid10357096>{{Cite journal  | last1 = Looijenga | first1 = LH. | last2 = Oosterhuis | first2 = JW. | title = Pathogenesis of testicular germ cell tumours. | journal = Rev Reprod | volume = 4 | issue = 2 | pages = 90-100 | month = May | year = 1999 | doi =  | PMID = 10357096 }}</ref>
*[[Isochromosome 12p]].<ref name=pmid10357096>{{Cite journal  | last1 = Looijenga | first1 = LH. | last2 = Oosterhuis | first2 = JW. | title = Pathogenesis of testicular germ cell tumours. | journal = Rev Reprod | volume = 4 | issue = 2 | pages = 90-100 | month = May | year = 1999 | doi =  | PMID = 10357096 }}</ref>
** Isochromosome = one arm (p or q) is lost and replaced with a duplicate of the remaining one.
** Isochromosome = one arm (p or q) is lost and replaced with a duplicate of the remaining one.
***Example: isochromosome p12 = chromosome 12 where q is lost and two p arms are present.<ref>URL: [http://ghr.nlm.nih.gov/handbook/illustrations/isochromosomes http://ghr.nlm.nih.gov/handbook/illustrations/isochromosomes]. Accessed on: 15 February 2012.</ref>
***Example: isochromosome 12p = chromosome 12 where q is lost and two p arms are present.<ref>URL: [http://ghr.nlm.nih.gov/handbook/illustrations/isochromosomes http://ghr.nlm.nih.gov/handbook/illustrations/isochromosomes]. Accessed on: 15 February 2012.</ref>


==Germinoma==
==Germinoma==
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Image: [http://path.upmc.edu/cases/case525/images/fig02a.jpg Germinoma (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case525.html http://path.upmc.edu/cases/case525.html]. Accessed on: 25 January 2012.</ref>
Image: [http://path.upmc.edu/cases/case525/images/fig02a.jpg Germinoma (upmc.edu)].<ref>URL: [http://path.upmc.edu/cases/case525.html http://path.upmc.edu/cases/case525.html]. Accessed on: 25 January 2012.</ref>
<gallery>
Image:Neuropathology_case_VIII_01.jpg | Germinoma  of the brain, low mag. (WC/jensflorian)
Image:Neuropathology_case_VIII_02.jpg | Germinoma intermed. mag. (WC/jensflorian)
Image:Neuropathology_case_VIII_03.jpg | Germinoma very high. mag. (WC/jensflorian)
Image:Neuropathology_case_VIII_05.jpg | Germinoma Oct3/4 staining (WC/jensflorian)
</gallery>


===Seminoma===
===Seminoma===
{{Main|Testis#Seminoma}}
{{Main|Seminoma}}
A common GCT in males.
A common GCT in males.


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==Yolk sac tumour==
==Yolk sac tumour==
===General===
{{Main|Yolk sac tumour}}
*Tumour also known as ''endodermal sinus tumour''.
 
====Epidemiology====
*Most common GCT in infants and young boys.
 
===Microscopic===
Classic feature:<ref name=Ref_PCPBoD8_510>{{Ref PCPBoD8|510}}</ref>
*Schiller-Duval bodies.
**Look like glomerulus - central blood vessel surrounded by epithelial-like cells a space and more epithelial-like cells
*Architecure - variable.
*#Reticular - most common according to WMSP.<ref name=Ref_WMSP369>{{Ref WMSP|369}}</ref>
*#Microcystic - most common according to ''webpathology.com''.<ref name=webpath_case34>URL: [http://webpathology.com/image.asp?case=34&n=1 http://webpathology.com/image.asp?case=34&n=1]. Accessed on: March 8, 2010.</ref> 
*#*Lace-like pattern.
*#Endodermal sinus-like - has Schiller-Duval bodies.
*#Solid.
*#Papillary.
*#Glandular.
*#Alveolar.
*#Enteric.
*#Polyvesicular vitelline.
*#Hepatoid.
*+/-Eosinophilic hyaline globules (contain alpha-fetoprotein).
 
Notes:
*Has a loose stroma/vaguely discohesive -- unlike embryonal carcinoma.
 
Variants:
*Hepatoid pattern.<ref>URL: [http://webpathology.com/image.asp?case=34&n=6 http://webpathology.com/image.asp?case=34&n=6]. Accessed on: March 8, 2010.</ref>
**Vaguely resembles liver.
***[[Hyaline globules]] (light red well-circumscribed globs).
***Bile canaculi.
*Solid pattern.<ref>URL: [http://webpathology.com/image.asp?case=34&n=8 http://webpathology.com/image.asp?case=34&n=8]. Accessed on: March 8, 2010.</ref>
**Vaguely resembles ''seminoma''.
 
Images:
*[http://webpathology.com/image.asp?case=34&n=6 Hepatoid Pattern (webpathology.com)].
*[http://www.webpathology.com/image.asp?case=34&n=5 Schiller-Duval body (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=6&Case=34 Hyaline globules (webpathology.com)].
*[http://path.upmc.edu/cases/case152.html Yolk sac tumour - case 1 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case492.html Yolk sca tumour - case 2 - several images (upmc.edu)].
 
===IHC===
*AFP +ve.
*Glypican 3 +ve.
**More sensitive than AFP.<ref name=pmid20438407>{{Cite journal  | last1 = Emerson | first1 = RE. | last2 = Ulbright | first2 = TM. | title = Intratubular germ cell neoplasia of the testis and its associated cancers: the use of novel biomarkers. | journal = Pathology | volume = 42 | issue = 4 | pages = 344-55 | month = Jun | year = 2010 | doi = 10.3109/00313021003767355 | PMID = 20438407 }}</ref>
*Alpha-1 AT +ve.
*Cytokeratin +ve. ???
 
===DDx===
*Embryonal carcinoma.


==Embryonal carcinoma==
==Embryonal carcinoma==
===General===
{{Main|Embryonal carcinoma}}
*Affects young adults.
**May be seen in women.
 
===Microscopic===
Features:<ref name=Ref_GUP549>{{Ref GUP|549}}</ref>
#Nucleoli - '''key feature'''.
#Vesicular nuclei (clear, empty appearing nuclei) - '''key feature'''.
#Nuclei overlap.
#[[Necrosis]] - common.
#*Not commonly present in seminoma.
#Indistinct cell borders
#Mitoses - common.
#Variable architecture:
#*Tubulopapillary.
#*Glandular.
#*Solid.
#*Embryoid bodies - ball of cells in surrounded by empty space on three sides.
 
Notes:
*Cytoplasmic staining variable (eosinophilic to basophilic).
 
Images:
*Set 1:
**[http://commons.wikimedia.org/wiki/File:Embryonal_carcinoma_-_very_high_mag_-_cropped.jpg Embryonal carcinoma - very high mag. - cropped (WC)].
**[http://commons.wikimedia.org/wiki/File:Embryonal_carcinoma_-_high_mag.jpg Embryonal carcinoma - high mag. (WC)].
*Set 2:
**[http://commons.wikimedia.org/wiki/File:Embryonal_carcinoma_high_mag.jpg Embryonal carcinoma - high mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Embryonal_carcinoma_intermed_mag.jpg Embryonal carcinoma - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Embryonal_carcinoma_low_mag.jpg Embryonal carcinoma - low mag. (WC)].
 
===DDx===
*Yolk sac tumour.
 
===IHC===
*AE1/AE3 +ve.
*CD30 +ve.


==Choriocarcinoma==
==Choriocarcinoma==
===General===
{{Main|Choriocarcinoma}}
*Aggressive clinical course.
*Usually a mixed tumour, i.e. pure choriocarcinoma is rare, e.g. [[dysgerminoma]] + choriocarcinoma.
 
====Clinical====
*High beta-hCG -- usually > 10,000 IU.
*Vaginal bleeding.
*Occasionally thyrotoxicosis.<ref name=pmid8395487>{{Cite journal  | last1 = O'Reilly | first1 = S. | last2 = Lyons | first2 = DJ. | last3 = Harrison | first3 = M. | last4 = Gaffney | first4 = E. | last5 = Cullen | first5 = M. | last6 = Clancy | first6 = L. | title = Thyrotoxicosis induced by choriocarcinoma a report of two cases. | journal = Ir Med J | volume = 86 | issue = 4 | pages = 124, 127 | month =  | year =  | doi =  | PMID = 8395487 }}</ref>
 
====Epidemiology====
*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:
*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 - classically in the centre of the lesion.
*+/-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.
**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>
***Cytotrophoblasts 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> - usu. no staining.
*MUC-4 +ve.<ref name=pmid18059230>{{Cite journal  | last1 = Mao | first1 = TL. | last2 = Kurman | first2 = RJ. | last3 = Huang | first3 = CC. | last4 = Lin | first4 = MC. | last5 = Shih | first5 = IeM. | title = Immunohistochemistry of choriocarcinoma: an aid in differential diagnosis and in elucidating pathogenesis. | journal = Am J Surg Pathol | volume = 31 | issue = 11 | pages = 1726-32 | month = Nov | year = 2007 | doi = 10.1097/PAS.0b013e318058a529 | PMID = 18059230 }}</ref>
*Ki-67 +ve -- typically >30%.


==Teratoma==
==Teratoma==
===General===
{{Main|Teratoma}}
*May be benign or malignant.
*Are supposed to consists of all three [[germ layers]] - this is not always true.
*May be associated with sacral agenesis.<ref name=omim176450>{{OMIM|176450}}</ref>
 
====Classification====
#Mature.
#*Common in females.
#*Usually benign; however, mature component may give rise to a malignancy like elsewhere in the body.
#**Most common malignancy arising from a mature teratoma: [[squamous cell carcinoma]].
#*A special type of mature teratoma is ''fetus in fetu''; this can be thought of as a very well-developed mature teratoma.
#Immature.
#*Uncommon.
#*Malignant.
#Monodermal.
#*Rare.
#*Highly specialized.
 
===Mature teratoma===
Features - three germ cell layers (usually):<ref>{{cite book |author=Moore, Keith L.; Persaud, T.V.N.|title=The Developing Human: Clinically Oriented Embryology |publisher=Saunders |location= |year=2002 |pages= 83 |edition=7th |isbn=978-0721694122 |oclc= |doi= |accessdate=}}</ref>
#Endoderm:
#*Skin, (mature) CNS.
#Mesoderm:
#*Muscle, bone, connective tissue, blood.
#Ectoderm:
#*Internal organs.
 
Note:
*May consist of skin only - in which case it is commonly called a ''dermoid''.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Teratoma_2_low_mag.jpg Mature teratoma - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Teratoma_2_high_mag.jpg Mature teratoma - high mag. (WC)].
 
===Immature teratoma===
Features:
*Immature if neural tissue is present:<ref>RS. 2 May 2010.</ref>
**Vaguely resembles pseudostratified respiratory epithelium.
*Islands of small hyperchromatic cells - "blastema".
*+/-Cartilage.
*+/-Adipocytes.
*+/-Colonic type mucosa.
*+/-Stratified squamous epithelium (skin).
 
Images:
*[http://commons.wikimedia.org/wiki/File:Immature_teratoma_high_mag.jpg Primitive neuroepithelium - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Primitive_neuroepithelium_intermed_mag.jpg Primitive neuroepithelium - intermed mag. (WC)]
*[http://commons.wikimedia.org/wiki/File:Teratoma_intermed_mag.jpg Teratoma - mature components (WC)].
 
Other images:
*[http://www.webpathology.com/image.asp?n=5&Case=35 Immature teratoma - myxomatous stroma (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=6&Case=35 Immature teratoma - blastema (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=7&Case=35 Immature teratoma - primitive neuroepithelium (webpathology.com)].
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/N0C001-PQ01-M.htm Immature teratoma - primitive neuroepithelium (ouhsc.edu)].
 
====Grading (immature)====
Based on quantity of immature neuroepithelium:<ref name=pmid17080330>{{cite journal |author=Harms D, Zahn S, Göbel U, Schneider DT |title=Pathology and molecular biology of teratomas in childhood and adolescence |journal=Klin Padiatr |volume=218 |issue=6 |pages=296–302 |year=2006 |pmid=17080330 |doi=10.1055/s-2006-942271 |url=}}</ref><ref name=pmid15761467>{{cite journal |author=Ulbright TM |title=Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues |journal=Mod. Pathol. |volume=18 Suppl 2 |issue= |pages=S61–79 |year=2005 |month=February |pmid=15761467 |doi=10.1038/modpathol.3800310 |url=http://www.nature.com/modpathol/journal/v18/n2s/full/3800310a.html}}</ref><ref name=pmid7814189>{{cite journal |author=O'Connor DM, Norris HJ |title=The influence of grade on the outcome of stage I ovarian immature (malignant) teratomas and the reproducibility of grading |journal=Int. J. Gynecol. Pathol. |volume=13 |issue=4 |pages=283–9 |year=1994 |month=October |pmid=7814189 |doi= |url=}}</ref>
*G0 - mature teratoma; no immature neuroepithelium.
*G1 - less than one lower power field ([[LPF]]) of immature neuroepithelium; LPF defined field at 4X magnification.
*G2 - 1-3 LPFs.
*G3 - more than 3 LPFs.
 
Note:
*LPF not adequately defined - see [[LPFitis]]. Same BS as HPF.
 
====IHC (immature)====
Features:
*Primitive neuroepithelium:<ref name=pmid11598856>{{cite journal |author=Craver RD, Lipscomb JT, Suskind D, Velez MC |title=Malignant teratoma of the thyroid with primitive neuroepithelial and mesenchymal sarcomatous components |journal=Ann Diagn Pathol |volume=5 |issue=5 |pages=285–92 |year=2001 |month=October |pmid=11598856 |doi=10.1053/adpa.2001.27918 |url=}}</ref>
**Neuron-specific enolase (NSE) +ve.
**Neuron-specific B tubulin +ve.
**Synaptophysin +ve.
 
===Monodermal teratomas===
====Struma ovarii====
Features:
*Thyroid tissue present - colloid is seen.
**May develop pathologies seen in the [[thyroid gland]], e.g. [[papillary thyroid carcinoma]].
 
Images:
*[http://commons.wikimedia.org/wiki/File:Struma_ovarii_-_low_mag.jpg Struma ovarii - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Struma_ovarii_-_high_mag.jpg Struma ovarii - high mag. (WC)].
 
====Strumal carcinoid====
Features:<ref name=pmid18509188>{{Cite journal  | last1 = Gorin | first1 = I. | last2 = Sastre-Garau | first2 = X. | title = Strumal carcinoid tumor of the ovary. | journal = J Clin Oncol | volume = 26 | issue = 16 | pages = 2780-1 | month = Jun | year = 2008 | doi = 10.1200/JCO.2008.16.1620 | PMID = 18509188 }}</ref><ref>{{Cite journal  | last1 = Tamsen | first1 = A. | last2 = Mazur | first2 = MT. | title = Ovarian strumal carcinoid in association with multiple endocrine neoplasia, type IIA. | journal = Arch Pathol Lab Med | volume = 116 | issue = 2 | pages = 200-3 | month = Feb | year = 1992 | doi =  | PMID = 1346363 }}</ref>
*Has components that suggest:
*#Carcinoid ([[neuroendocrine tumour]]).
*#*Nuclei with stippled chromatin (salt-and-pepper chromatin).
*#[[Thyroid]] - cystic spaces/follicular-like structures.
 
Images:
*[http://commons.wikimedia.org/wiki/File:Strumal_carcinoid_-_intermed_mag.jpg Strumal carcinoid - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Strumal_carcinoid_-_high_mag.jpg Strumal carcinoid - high mag. (WC)].


==Gonadoblastoma==
==Gonadoblastoma==
===General===
{{Main|Gonadoblastoma}}
*Associated with abnormal sexual development.
*Often coexist with a [[dysgerminoma]].
*A mixed tumour that consists of (1) primitive germ cells and (2) sex cord elements.
 
===Gross===
*+/-Cystic.
 
===Microscopic===
Features:<ref name=Ref_PBoD1104>{{Ref PBoD|1104}}</ref>
*Immature germ cells resembling Sertoli cells or granulosa cells.
**Sertoli cells = moderate cytoplasm in a trabecular or tubular architecture.
**Granulosa cells = form follicle-like structures.
***May form nests.
*Primitive germ cells resemble those of a [[dysgerminoma]].
**Polygonal cells with a central nucleus, squared-off nuclear membrane and clear cytoplasm.
*+/-Calcification (very common).
*+/-Eosinophilic basement membrane material between the (primitive) germ cells and support cells.<ref>URL: [http://www.flickr.com/photos/ckrishnan/3972432044/in/photostream/ http://www.flickr.com/photos/ckrishnan/3972432044/in/photostream/]. Accessed on: 11 September 2011.</ref>
 
Images:
*www:
**[http://www.webpathology.com/image.asp?n=40&Case=532 Gonadoblastoma - low mag. (webpathology.com)].
**[http://www.webpathology.com/image.asp?case=532&n=42 Gonadoblastoma - high mag. (webpathology.com)].
**[http://www.webpathology.com/image.asp?case=532&n=44 Gonadoblastoma - high mag. (webpathology.com)].
**[http://www.flickr.com/photos/ckrishnan/3972431774/in/photostream/ Gonadoblastoma - low mag. (flickr.com)].
**[http://www.flickr.com/photos/ckrishnan/3972432404/in/photostream/ Gonadoblastoma - intermed. mag. (flickr.com)].
**[http://www.flickr.com/photos/ckrishnan/3972432044/in/photostream/ Gonadoblastoma - high mag. (flickr.com)].
**[http://path.upmc.edu/cases/case356.html Gonadoblastoma - several cases (upmc.edu)].
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Gonadoblastoma_-_intermed_mag.jpg Gonadoblastoma - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Gonadoblastoma_-_b_-_high_mag.jpg Gonadoblastoma - high mag. (WC)].


==Polyembryoma==
==Polyembryoma==
===General===
{{Main|Polyembryoma}}
*Poor prognosis.
*Almost never in pure form, i.e. usu. a component of a [[mixed germ cell tumour]].<ref>{{Cite journal  | last1 = Young | first1 = RH. | title = Testicular tumors--some new and a few perennial problems. | journal = Arch Pathol Lab Med | volume = 132 | issue = 4 | pages = 548-64 | month = Apr | year = 2008 | doi = 10.1043/1543-2165(2008)132[548:TTNAAF]2.0.CO;2 | PMID = 18384207 }}</ref>
 
===Microscopic===
Features:
*Disc shaped structure (embryo-like) with:
**The one side endoderm.
***Skin/CNS.
**The other side ectoderm.
***Internal organs - GI tract.
 
Images:
*[http://www.webpathology.com/image.asp?case=37&n=6 Polyembryoma - low mag. (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=7&Case=37 Polyembryoma - high mag. (webpathology.com)].


==Mixed germ cell tumour==
==Mixed germ cell tumour==
===General===
{{Main|Mixed germ cell tumour}}
*60% of GCTs are mixed.
 
Common combinations:
# Teratoma + embryonal carcinoma + endodermal sinus tumour (yolk sac tumour) (TEE).
# Seminoma + embryonal (SE).
# Teratoma + embryonal +(TE).
 
Memory device: ''TEE'' + all combinations have embryonal carcinoma.
===Microscopic===
Features:
*Depends on components.
 
Notes:
*If one cannot identify the component... it is probably yolk sac as this has so many different patterns.
 
Images:
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Mixed_germ_cell_tumour_-_intermed_mag.jpg Mixed germ cell tumour - intermed mag. (WC)].
*www:
**[http://path.upmc.edu/cases/case192/micro.html Mixed germ cell tumour - several images (upmc.edu)].
**[http://path.upmc.edu/cases/case356.html Mixed germ cell tumour - several cases (upmc.edu)].
 
===IHC===
*Beta-hCG +ve - if syncytiotrophoblasts are present.
*AFP +ve - a yolk sac tumour component is present.
*GFAP +ve - if neuroepithelium is present.


==See also==
==See also==
Line 440: Line 177:
*[[Ovarian tumours]].
*[[Ovarian tumours]].
*[[Trophoblast]].
*[[Trophoblast]].
*[[Sex cord-stromal tumours]].


==References==
==References==
Line 446: Line 184:
[[Category:Gynecologic pathology]]
[[Category:Gynecologic pathology]]
[[Category:Genitourinary pathology]]
[[Category:Genitourinary pathology]]
[[Category:Germ cell tumours|Germ cell tumours]]
Michael
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