Difference between revisions of "Germ cell tumours"

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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]].


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===Grossing===
===Grossing===
*1 cm^2 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>
{{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===
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! 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]]
| [[Image:Intratubular_germ_cell_neoplasia_high_mag_cropped.jpg|thumb|center|150px|ITGCN (WC/Nephron)]]
| [[Image:Intratubular_germ_cell_neoplasia_high_mag_cropped.jpg|thumb|center|150px|GCNIS (WC/Nephron)]]
|-  
|-  
| [[Germinoma]] / [[Seminoma]] / [[Dysgerminoma]]
| [[Germinoma]] / [[Seminoma]] / [[Dysgerminoma]]
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| 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
| [[Image:Mixed_germ_cell_tumour_-_very_high_mag.jpg|thumb|center|150px|Yolk sac tumour (WC)]]
| [[Image:Mixed_germ_cell_tumour_-_very_high_mag.jpg|thumb|center|150px|Yolk sac tumour (WC)]]
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| 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  
| [[Image:Embryonal_carcinoma_high_mag.jpg|thumb|center|150px|Embryonal carcinoma (WC/Nephron)]]
| [[Image:Embryonal_carcinoma_high_mag.jpg|thumb|center|150px|Embryonal carcinoma (WC/Nephron)]]
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| 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]]
| [[Image:Choriocarcinoma_-2-_very_high_mag.jpg|thumb|center|150px|Choriocarcinoma. (WC/Nephron)]]
| [[Image:Choriocarcinoma_-2-_very_high_mag.jpg|thumb|center|150px|Choriocarcinoma. (WC/Nephron)]]
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===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===
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==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)].
<gallery>
Image:Gonadoblastoma_-_intermed_mag.jpg | Gonadoblastoma - intermed. mag. (WC/Nephron)
Image:Gonadoblastoma_-_b_-_high_mag.jpg | Gonadoblastoma - high mag. (WC/Nephron)
</gallery>
==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====
<gallery>
Image:Mixed_germ_cell_tumour_-_intermed_mag.jpg | Mixed GCT - intermed mag. (WC/Nephron)
Image:Mixed germ cell tumour - high mag.jpg | Mixed GCT - high mag. (WC/Nephron)
</gallery>
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==
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*[[Ovarian tumours]].
*[[Ovarian tumours]].
*[[Trophoblast]].
*[[Trophoblast]].
*[[Sex cord-stromal tumours]].


==References==
==References==
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