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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{{familytree | | | | | B01 | | | | | | | | | | | | | | B02 | | | | | | | | | | |B01=OCT4 +ve | B02=OCT4 -ve}}
{{familytree | | | | | B01 | | | | | | | | | | | | | | B02 | | | | | | | | | | |B01=OCT4 +ve | B02=OCT4 -ve}}
{{familytree | |,|-|-|-|^|-|-|-|.| | | | | |,|-|-|-|-|-|+|-|-|-|-|-|.| | | | | |}}
{{familytree | |,|-|-|-|^|-|-|-|.| | | | | |,|-|-|-|-|-|+|-|-|-|-|-|.| | | | | |}}
{{familytree | C01 | | | | | | C02 | | | | C03 | | | | C04 | | | | C05 | | | | |C01=CD117 +ve<br>CD30 -ve |C02= CD117 -ve<br>CD30 +ve|C03=Glypican3 +ve<br>AFP +ve<br>beta-hCG -ve|C04=Glypican3 ?<br>AFP -ve<br>beta-hCG +ve|C05=Glypican3 -ve<br>AFP -ve<br>beta-hCG -ve}}
{{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 | |!| | | | | | | |!| | | | | |!| | | | | |!| | | | | |!| | | | | |}}
{{familytree | D01 | | | | | | D02 | | | | D03 | | | | D04 | | | | D05 | | | | |D01=[[Seminoma]]|D02=[[Embryonal carcinoma]]|D03=[[Yolk sac tumour]]|D04=[[Choriocarcinoma]] |D05= [[Spermatocytic seminoma]] }}
{{familytree | D01 | | | | | | D02 | | | | D03 | | | | D04 | | | | D05 | | | | |D01=[[Seminoma]]|D02=[[Embryonal carcinoma]]|D03=[[Yolk sac tumour]]|D04=[[Choriocarcinoma]] |D05= [[Spermatocytic seminoma]] }}
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====GCT versus sex cord-stromal tumour====
====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>
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.<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>
*[[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]]).
*Alpha-inhibin -ve (+ve in [[SCST]]).
*Calretinin -ve (+ve in SCST).
*Calretinin -ve (+ve in SCST).
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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===

Latest revision as of 16:36, 13 October 2023

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.

Overview

Germ cell tumour - types

Precusor:

Germ cell tumours (GCTs):

Grossing

Main article: Orchiectomy
  • 1 cm2 of tumour per cm of maximal tumour dimension - guideline for testicular cancer.[1]

IHC for GCTs

ISUP

An algorithmic approach based on the ISUP consensus paper by Ulbright et al.:[2]

 
 
 
 
 
 
 
 
 
 
 
 
Germ cell tumours
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
OCT4 +ve
 
 
 
 
 
 
 
 
 
 
 
 
 
OCT4 -ve
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CD117 +ve
CD30 -ve
 
 
 
 
 
CD117 -ve
CD30 +ve
 
 
 
Glypican 3 +ve
AFP +ve
beta-hCG -ve
 
 
 
Glypican 3 ?
AFP -ve
beta-hCG +ve
 
 
 
Glypican 3 -ve
AFP -ve
beta-hCG -ve
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Seminoma
 
 
 
 
 
Embryonal carcinoma
 
 
 
Yolk sac tumour
 
 
 
Choriocarcinoma
 
 
 
Spermatocytic seminoma
 
 
 
 

ABCDs of GCTs

  • AFP - yolk sac tumour.
  • Beta-hCG - choriocarcinoma.
  • CD30 - embryonal carcinoma.
  • D2-40 - seminoma.

GCT versus sex cord-stromal tumour

The ISUP recommends:[3]

  • SALL4 +ve (in GCTs).[4]
  • Alpha-inhibin -ve (+ve in SCST).
  • Calretinin -ve (+ve in SCST).

Alternates for SALL4 are:[3]

  • OCT4 and GPC3.

Tabular summary of GCTs

Tumour Key feature Microscopic IHC Other Image
Germ cell neoplasia in situ (GCNIS) nests of small fried egg cells large central nucleus, clear
cytoplasm, squared-off nuclear membrane, nucleoli[5] 		CD117 +ve, CD30 -ve appearance similar to seminoma
GCNIS (WC/Nephron)
Germinoma / Seminoma / Dysgerminoma fried egg cells fried egg-like cells (central nucleus, clear
cytoplasm) with squared-off nuclear
membrane, nucleoli, lymphocytic infiltrate, granulomata,
syncytiotrophoblastic giant cells[6] 		D2-40 seminoma = male version of this tumour; dysgerminoma = female version of this tumour
Seminoma (WC/Nephron)
Yolk sac tumour (endodermal sinus tumour) Schiller-Duval bodies Schiller-Duval b. = central blood vessel surrounded by epithelial-like cells a space and more epithelial-like cells, variable arch. AFP +ve, Glypican 3 +ve patterns: microcystic, solid, hepatoid
Yolk sac tumour (WC)
Embryonal carcinoma 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 CD30 +ve, CD117 -ve usu. part of a mixed GCT
Embryonal carcinoma (WC/Nephron)
Choriocarcinoma 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) beta-hCG +ve may be preceded by a complete hydatidiform mole
Choriocarcinoma. (WC/Nephron)
Teratoma, immature primitive neuroepithelium pseudostratified epithelium in rosettes (gland-like arrangement) None testicular teratomas in post-pubertal males are all considered malignant[7]
Primitive neuroepithelium (WC/Nephron)
Mixed germ cell tumour NA common combinations: teratoma + embryonal carcinoma + endodermal sinus tumour (yolk sac tumour) (TEE); seminoma + embryonal (SE); embryonal + teratoma (TE) NA -
Mixed GCT (WC/Nephron)
Gonadoblastoma primitive germ cells (central nucleus, moderate (eosinophilic) cytoplasm); sex cord element sex cord element may be either granulosa cells (follicle-like arch.) or Sertoli cells (trabecular arch.) ? often abnormal karyotype; usu. Y chromosome present
Gonadoblastoma (WC/Nephron)

Molecular pathology

Most common cytogenetic abnormality in GCTs:

  • Isochromosome 12p.[8]
    • Isochromosome = one arm (p or q) is lost and replaced with a duplicate of the remaining one.
      • Example: isochromosome 12p = chromosome 12 where q is lost and two p arms are present.[9]

Germinoma

Comes in three flavours:

  • Germinoma.
  • Seminoma.
  • Dysgerminoma.

Germinoma

Is the generic version of this tumour. It is found in the midline (brain, mediastinum).

Image: Germinoma (upmc.edu).[10]

  • Germinoma of the brain, low mag. (WC/jensflorian)

  • Germinoma intermed. mag. (WC/jensflorian)

  • Germinoma very high. mag. (WC/jensflorian)

  • Germinoma Oct3/4 staining (WC/jensflorian)


Seminoma

Main article: Seminoma

A common GCT in males.

Dysgerminoma

Main article: Ovarian tumours#Dysgerminoma

A common GCT in females.

Yolk sac tumour

Main article: Yolk sac tumour

Embryonal carcinoma

Main article: Embryonal carcinoma

Choriocarcinoma

Main article: Choriocarcinoma

Teratoma

Main article: Teratoma

Gonadoblastoma

Main article: Gonadoblastoma

Polyembryoma

Main article: Polyembryoma

Mixed germ cell tumour

Main article: Mixed germ cell tumour

See also

References

  1. ↑ URL: http://www.uroweb.org/gls/pdf/10_Testicular_Cancer.pdf. Accessed on: 30 October 2012.
  2. ↑ Ulbright TM, Tickoo SK, Berney DM, Srigley JR (August 2014). "Best practices recommendations in the application of immunohistochemistry in testicular tumors: report from the international society of urological pathology consensus conference". Am. J. Surg. Pathol. 38 (8): e50–9. doi:10.1097/PAS.0000000000000233. PMID 24832161.
  3. ↑ 3.0 3.1 Amin MB, Epstein JI, Ulbright TM, et al. (August 2014). "Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference". Am. J. Surg. Pathol. 38 (8): 1017–22. doi:10.1097/PAS.0000000000000254. PMID 25025364.
  4. ↑ Miettinen M, Wang Z, McCue PA, et al. (March 2014). "SALL4 expression in germ cell and non-germ cell tumors: a systematic immunohistochemical study of 3215 cases". Am. J. Surg. Pathol. 38 (3): 410–20. doi:10.1097/PAS.0000000000000116. PMID 24525512.
  5. ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 538. ISBN 978-0443066771.
  6. ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 542. ISBN 978-0443066771.
  7. ↑ Carver, BS.; Al-Ahmadie, H.; Sheinfeld, J. (May 2007). "Adult and pediatric testicular teratoma.". Urol Clin North Am 34 (2): 245-51; abstract x. doi:10.1016/j.ucl.2007.02.013. PMID 17484929.
  8. ↑ Looijenga, LH.; Oosterhuis, JW. (May 1999). "Pathogenesis of testicular germ cell tumours.". Rev Reprod 4 (2): 90-100. PMID 10357096.
  9. ↑ URL: http://ghr.nlm.nih.gov/handbook/illustrations/isochromosomes. Accessed on: 15 February 2012.
  10. ↑ URL: http://path.upmc.edu/cases/case525.html. Accessed on: 25 January 2012.
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