Difference between revisions of "Germ cell neoplasia in situ"

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'''Intratubular germ cell neoplasia''', abbreviated '''ITGCN''', is a premalignant lesion of the [[testis]].
{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Image      = Intratubular germ cell neoplasia - 2 - very high mag.jpg
| Width      =
| Caption    = GCNIS (left of image). [[H&E stain]].
| Synonyms  = intratubular germ cell neoplasia (old term)
| Micro      = "large" round or polygonal nuclei, prominent nucleoli, clear cytoplasm, +/-cells (completely) fill the tubule
| Subtypes  = undifferentiated, differentiated (intratubular seminoma, intratubular non-seminoma)
| LMDDx      = [[seminoma]], [[embryonal carcinoma]], Sertoli cell-only syndrome, [[mixed germ cell tumour]]
| Stains    =
| IHC        = OCT4, PLAP +ve, D2-40 +ve
| EM        =
| Molecular  =
| IF        =
| Gross      =
| Grossing  =
| Site      = [[testis]]
| Assdx      =
| Syndromes  =
| Clinicalhx =
| Signs      =
| Symptoms  =
| Prevalence =
| Bloodwork  =
| Rads      =
| Endoscopy  =
| Prognosis  = premalignant
| Other      =
| ClinDDx    =
| Tx        = radiotherapy (?)
}}
'''Germ cell neoplasia in situ''', abbreviated '''GCNIS''', is a premalignant lesion of the [[testis]].
 
It was previously known previously known as '''intratubular germ cell neoplasia''' (abbreviated '''ITGCN''') and '''testicular intraepithelial neoplasia'''.<ref name=pmid23293116 >{{Cite journal  | last1 = Dieckmann | first1 = KP. | last2 = Wilken | first2 = S. | last3 = Loy | first3 = V. | last4 = Matthies | first4 = C. | last5 = Kleinschmidt | first5 = K. | last6 = Bedke | first6 = J. | last7 = Martinschek | first7 = A. | last8 = Souchon | first8 = R. | last9 = Pichlmeier | first9 = U. | title = Treatment of testicular intraepithelial neoplasia (intratubular germ cell neoplasia unspecified) with local radiotherapy or with platinum-based chemotherapy: a survey of the German Testicular Cancer Study Group. | journal = Ann Oncol | volume = 24 | issue = 5 | pages = 1332-7 | month = May | year = 2013 | doi = 10.1093/annonc/mds628 | PMID = 23293116 }}</ref><ref name=pmid26918959>{{Cite journal  | last1 = Berney | first1 = DM. | last2 = Looijenga | first2 = L. | last3 = Idrees | first3 = M. | last4 = Oosterhuis | first4 = JW. | last5 = Rajpert-De Meyts | first5 = E. | last6 = Ulbright | first6 = TM. | last7 = Skakkebaek | first7 = NE. | title = Germ Cell Neoplasia In Situ (GCNIS). Evolution of the Current Nomenclature for Testicular Pre-invasive Germ Cell Malignancy. | journal = Histopathology | volume =  | issue =  | pages =  | month = Feb | year = 2016 | doi = 10.1111/his.12958 | PMID = 26918959 }}</ref>


==General==
==General==
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*Not all germ cell tumours (GCTs) arise from ''intratubular germ cell neoplasia''.  
*Not all germ cell tumours (GCTs) arise from ''intratubular germ cell neoplasia''.  


The following testicular GCTs do not arise from ITGCN:
The following testicular GCTs do not arise from GCNIS:
*[[Spermatocytic seminoma]].<ref>{{cite journal |author=Müller J, Skakkebaek NE, Parkinson MC |title=The spermatocytic seminoma: views on pathogenesis |journal=Int. J. Androl. |volume=10 |issue=1 |pages=147–56 |year=1987 |month=February |pmid=3583416 |doi= |url=}}</ref>
*[[Spermatocytic tumour]].<ref name=pmid2837162>{{cite journal |author=Müller J, Skakkebaek NE, Parkinson MC |title=The spermatocytic seminoma: views on pathogenesis |journal=Int. J. Androl. |volume=10 |issue=1 |pages=147–56 |year=1987 |month=February |pmid=3583416 |doi= |url=}}</ref>
*[[Yolk sac tumour]]s (endodermal sinus tumour).<ref>{{cite journal |author=Manivel JC, Simonton S, Wold LE, Dehner LP |title=Absence of intratubular germ cell neoplasia in testicular yolk sac tumors in children. A histochemical and immunohistochemical study |journal=Arch. Pathol. Lab. Med. |volume=112 |issue=6 |pages=641–5 |year=1988 |month=June |pmid=2837162 |doi= |url=}}</ref>
*[[Yolk sac tumour]]s (endodermal sinus tumour).<ref>{{cite journal |author=Manivel JC, Simonton S, Wold LE, Dehner LP |title=Absence of intratubular germ cell neoplasia in testicular yolk sac tumors in children. A histochemical and immunohistochemical study |journal=Arch. Pathol. Lab. Med. |volume=112 |issue=6 |pages=641–5 |year=1988 |month=June |pmid=2837162 |doi= |url=}}</ref>
*Teratoma.{{Fact}}
*Teratoma.{{Fact}}


Classification:<ref name=pmid11900581/>  
Classification:<ref name=pmid11900581/>  
*Undifferentiated ITGCN.
*Undifferentiated GCNIS.
*Differentiated ITGCN.<ref name=pmid17592271>{{Cite journal  | last1 = Lau | first1 = SK. | last2 = Weiss | first2 = LM. | last3 = Chu | first3 = PG. | title = Association of intratubular seminoma and intratubular embryonal carcinoma with invasive testicular germ cell tumors. | journal = Am J Surg Pathol | volume = 31 | issue = 7 | pages = 1045-9 | month = Jul | year = 2007 | doi = 10.1097/PAS.0b013e31802b8712 | PMID = 17592271 }}</ref>
*Differentiated GCNIS.<ref name=pmid17592271>{{Cite journal  | last1 = Lau | first1 = SK. | last2 = Weiss | first2 = LM. | last3 = Chu | first3 = PG. | title = Association of intratubular seminoma and intratubular embryonal carcinoma with invasive testicular germ cell tumors. | journal = Am J Surg Pathol | volume = 31 | issue = 7 | pages = 1045-9 | month = Jul | year = 2007 | doi = 10.1097/PAS.0b013e31802b8712 | PMID = 17592271 }}</ref>
**''Intratubular embryonal carcinoma''.
**''Intratubular seminoma.''
**''Intratubular seminoma.''
**''Intratubular non-seminoma''.
Treatment:
*Radiotherapy.<ref name=pmid23293116 >{{Cite journal  | last1 = Dieckmann | first1 = KP. | last2 = Wilken | first2 = S. | last3 = Loy | first3 = V. | last4 = Matthies | first4 = C. | last5 = Kleinschmidt | first5 = K. | last6 = Bedke | first6 = J. | last7 = Martinschek | first7 = A. | last8 = Souchon | first8 = R. | last9 = Pichlmeier | first9 = U. | title = Treatment of testicular intraepithelial neoplasia (intratubular germ cell neoplasia unspecified) with local radiotherapy or with platinum-based chemotherapy: a survey of the German Testicular Cancer Study Group. | journal = Ann Oncol | volume = 24 | issue = 5 | pages = 1332-7 | month = May | year = 2013 | doi = 10.1093/annonc/mds628 | PMID = 23293116 }}</ref>


==Microscopic==
==Microscopic==
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**Polygonal nuclei = squared-off nuclear membrane.
**Polygonal nuclei = squared-off nuclear membrane.
*Prominent nucleoli - '''key feature'''.
*Prominent nucleoli - '''key feature'''.
*Clear cytoplasm.
*Clear cytoplasm - '''important'''.
*+/-Cells fill the tubule.
*+/-Cells fill the tubule.
Note:
*Sertoli cells may have a nucleolus... but they have eosinophilic ctyoplasm.{{fact}}


DDx:
DDx:
*Sertoli cell-only syndrome - Sertoli cells also have nucleoli, wind swept appearance.<ref>URL: [http://www.webpathology.com/image.asp?n=3&Case=28 http://www.webpathology.com/image.asp?n=3&Case=28]. Accessed on: 25 March 2013.</ref>
*Sertoli cell-only syndrome - Sertoli cells also have nucleoli, wind swept appearance.<ref>URL: [http://www.webpathology.com/image.asp?n=3&Case=28 http://www.webpathology.com/image.asp?n=3&Case=28]. Accessed on: 25 March 2013.</ref>
*[[Seminoma]] - especially intratubular predominant growth pattern.
*[[Embryonal carcinoma]].
*[[Mixed germ cell tumour]].


===Images===
===Images===
====Case 1====
<gallery>
<gallery>
Image: Intratubular germ cell neoplasia - intermed mag.jpg | ITGCN - intermed. mag.
Image: Intratubular germ cell neoplasia - intermed mag.jpg | GCNIS (ITGCN) - intermed. mag.
Image: Intratubular germ cell neoplasia - high mag.jpg | ITGCN - high mag.
Image: Intratubular germ cell neoplasia - high mag.jpg | GCNIS (ITGCN) - high mag.
Image: Intratubular germ cell neoplasia - very high mag.jpg | ITGCN - very high mag.
Image: Intratubular germ cell neoplasia - very high mag.jpg | GCNIS (ITGCN) - very high mag.
Image: Intratubular germ cell neoplasia - 2 - very high mag.jpg | ITGCN - very high mag.
Image: Intratubular germ cell neoplasia - 2 - very high mag.jpg | GCNIS (ITGCN) - very high mag.
</gallery>
</gallery>
====Case 2====
<gallery>
<gallery>
Image:Intratubular_germ_cell_neoplasia_high_mag_cropped.jpg | ITGCN - cropped. (WC/Nephron)
Image:Intratubular_germ_cell_neoplasia_high_mag_cropped.jpg | GCNIS (ITGCN) - cropped. (WC/Nephron)
Image:Intratubular_germ_cell_neoplasia_high_mag.jpg | ITGCN. (WC/Nephron)
Image:Intratubular_germ_cell_neoplasia_high_mag.jpg | GCNIS (ITGCN). (WC/Nephron)
</gallery>
</gallery>
www:
====Case 3====
<gallery>
Image: ITGCN and Sertoli cells only -- intermed mag.jpg | GCNIS (ITGCN) & SCO - intermed. mag.
Image: ITGCN and Sertoli cells only -- high mag.jpg | GCNIS (ITGCN) & SCO - high mag.
 
Image: ITGCN and Sertoli cells only - PLAP -- intermed mag.jpg | GCNIS (ITGCN) & SCO - intermed. mag.
Image: ITGCN and Sertoli cells only - PLAP -- high mag.jpg | GCNIS (ITGCN) & SCO - high mag.
Image: ITGCN and Sertoli cells only - PLAP -- very high mag.jpg | GCNIS (ITGCN) & SCO - very high mag.
</gallery>
====www====
*[http://www.webpathology.com/image.asp?case=30&n=1 ITGCN (webpathology.com)].
*[http://www.webpathology.com/image.asp?case=30&n=1 ITGCN (webpathology.com)].
*[http://www.archivesofpathology.org/na101/home/literatum/publisher/pinnacle/journals/content/arpa/2002/15432165-126.4/0003-9985%282002%29126%3C0487%3Aiec%3E2.0.co%3B2/production/images/large/i1543-2165-126-4-487-f01.jpeg Intratubular embryonal carcinoma (archivesofpathology.org)].<ref name=pmid11900581/>
*[http://www.archivesofpathology.org/na101/home/literatum/publisher/pinnacle/journals/content/arpa/2002/15432165-126.4/0003-9985%282002%29126%3C0487%3Aiec%3E2.0.co%3B2/production/images/large/i1543-2165-126-4-487-f01.jpeg Intratubular embryonal carcinoma (archivesofpathology.org)].<ref name=pmid11900581/>


==IHC==
==IHC==
Features:<ref name=pmid15221945>{{Cite journal  | last1 = Honecker | first1 = F. | last2 = Stoop | first2 = H. | last3 = de Krijger | first3 = RR. | last4 = Chris Lau | first4 = YF. | last5 = Bokemeyer | first5 = C. | last6 = Looijenga | first6 = LH. | title = Pathobiological implications of the expression of markers of testicular carcinoma in situ by fetal germ cells. | journal = J Pathol | volume = 203 | issue = 3 | pages = 849-57 | month = Jul | year = 2004 | doi = 10.1002/path.1587 | PMID = 15221945 }}</ref>
===ISUP consensus===
*PLAP +ve.<ref>{{Cite journal  | last1 = Schreiber | first1 = L. | last2 = Lifschitz-Mercer | first2 = B. | last3 = Paz | first3 = G. | last4 = Yavetz | first4 = H. | last5 = Elliott | first5 = DJ. | last6 = Kula | first6 = K. | last7 = Slowikowska-Hilczer | first7 = J. | last8 = Maymon | first8 = BB. | title = Double immunolabeling by the RBM and the PLAP markers for identifying intratubular (in situ) germ cell neoplasia of the testis. | journal = Int J Surg Pathol | volume = 11 | issue = 1 | pages = 17-20 | month = Jan | year = 2003 | doi =  | PMID = 12598912 }}</ref>
GCNIS (ITGCN) versus atypical intratubular germ cells:<ref name=pmid25025364>{{Cite journal  | last1 = Amin | first1 = MB. | last2 = Epstein | first2 = JI. | last3 = Ulbright | first3 = TM. | last4 = Humphrey | first4 = PA. | last5 = Egevad | first5 = L. | last6 = Montironi | first6 = R. | last7 = Grignon | first7 = D. | last8 = Trpkov | first8 = K. | last9 = Lopez-Beltran | first9 = A. | 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 | month = Aug | year = 2014 | doi = 10.1097/PAS.0000000000000254 | PMID = 25025364 }}</ref>
*OCT4 +ve.
 
Alternates:
*[[PLAP]] +ve.<ref name=pmid12598912>{{Cite journal  | last1 = Schreiber | first1 = L. | last2 = Lifschitz-Mercer | first2 = B. | last3 = Paz | first3 = G. | last4 = Yavetz | first4 = H. | last5 = Elliott | first5 = DJ. | last6 = Kula | first6 = K. | last7 = Slowikowska-Hilczer | first7 = J. | last8 = Maymon | first8 = BB. | title = Double immunolabeling by the RBM and the PLAP markers for identifying intratubular (in situ) germ cell neoplasia of the testis. | journal = Int J Surg Pathol | volume = 11 | issue = 1 | pages = 17-20 | month = Jan | year = 2003 | doi =  | PMID = 12598912 }}</ref>
*D2-40 +ve.
 
===Others===
*CD117 +ve.  
*CD117 +ve.  
**Disputed: doesn't differentiate neoplastic from non-neoplastic according to Biermann ''et al''.<ref name=pmid22340755>{{Cite journal  | last1 = Biermann | first1 = K. | last2 = Stoop | first2 = H. | last3 = Looijenga | first3 = L. | title = c-KIT protein expression does not discriminate neoplastic from non-neoplastic intratubular germ cells. | journal = Histopathology | volume = 60 | issue = 6 | pages = 1017-9 | month = May | year = 2012 | doi = 10.1111/j.1365-2559.2011.04157.x | PMID = 22340755 }}</ref>
**Disputed: doesn't differentiate neoplastic from non-neoplastic according to Biermann ''et al''.<ref name=pmid22340755>{{Cite journal  | last1 = Biermann | first1 = K. | last2 = Stoop | first2 = H. | last3 = Looijenga | first3 = L. | title = c-KIT protein expression does not discriminate neoplastic from non-neoplastic intratubular germ cells. | journal = Histopathology | volume = 60 | issue = 6 | pages = 1017-9 | month = May | year = 2012 | doi = 10.1111/j.1365-2559.2011.04157.x | PMID = 22340755 }}</ref>
*OCT3/4 +ve.
*OCT3/4 +ve.
Note:
*Normal testis PLAP -ve, CD117 -ve.<ref name=pmid9104938>{{Cite journal  | last1 = Hawkins | first1 = E. | last2 = Heifetz | first2 = SA. | last3 = Giller | first3 = R. | last4 = Cushing | first4 = B. | title = The prepubertal testis (prenatal and postnatal): its relationship to intratubular germ cell neoplasia: a combined Pediatric Oncology Group and Children's Cancer Study Group. | journal = Hum Pathol | volume = 28 | issue = 4 | pages = 404-10 | month = Apr | year = 1997 | doi =  | PMID = 9104938 }}</ref>


==See also==
==See also==

Latest revision as of 04:41, 22 March 2016

Germ cell neoplasia in situ
Diagnosis in short

GCNIS (left of image). H&E stain.
Synonyms intratubular germ cell neoplasia (old term)
LM "large" round or polygonal nuclei, prominent nucleoli, clear cytoplasm, +/-cells (completely) fill the tubule
Subtypes undifferentiated, differentiated (intratubular seminoma, intratubular non-seminoma)
LM DDx seminoma, embryonal carcinoma, Sertoli cell-only syndrome, mixed germ cell tumour
IHC OCT4, PLAP +ve, D2-40 +ve
Site testis
Prognosis premalignant
Treatment radiotherapy (?)

Germ cell neoplasia in situ, abbreviated GCNIS, is a premalignant lesion of the testis.

It was previously known previously known as intratubular germ cell neoplasia (abbreviated ITGCN) and testicular intraepithelial neoplasia.[1][2]

General

  • Considered the precursor lesion for germ cell tumours.
  • Not all germ cell tumours (GCTs) arise from intratubular germ cell neoplasia.

The following testicular GCTs do not arise from GCNIS:

Classification:[5]

  • Undifferentiated GCNIS.
  • Differentiated GCNIS.[6]
    • Intratubular seminoma.
    • Intratubular non-seminoma.

Treatment:

  • Radiotherapy.[1]

Microscopic

Features:[7][8]

  • "Large" round or polygonal nuclei.
    • Size in relation to normal often not defined.
      • Rakheja et al. say >= 5x a lymphocyte for intratubular embryonal carcinoma.[5]
    • Polygonal nuclei = squared-off nuclear membrane.
  • Prominent nucleoli - key feature.
  • Clear cytoplasm - important.
  • +/-Cells fill the tubule.

Note:

  • Sertoli cells may have a nucleolus... but they have eosinophilic ctyoplasm.[citation needed]

DDx:

Images

Case 1

  • GCNIS (ITGCN) - intermed. mag.

  • GCNIS (ITGCN) - high mag.

  • GCNIS (ITGCN) - very high mag.

  • GCNIS (ITGCN) - very high mag.

Case 2

  • GCNIS (ITGCN) - cropped. (WC/Nephron)

  • GCNIS (ITGCN). (WC/Nephron)

Case 3

  • GCNIS (ITGCN) & SCO - intermed. mag.

  • GCNIS (ITGCN) & SCO - high mag.

  • GCNIS (ITGCN) & SCO - intermed. mag.

  • GCNIS (ITGCN) & SCO - high mag.

  • GCNIS (ITGCN) & SCO - very high mag.

www

IHC

ISUP consensus

GCNIS (ITGCN) versus atypical intratubular germ cells:[10]

  • OCT4 +ve.

Alternates:

Others

  • CD117 +ve.
    • Disputed: doesn't differentiate neoplastic from non-neoplastic according to Biermann et al.[12]
  • OCT3/4 +ve.

See also

References

  1. ↑ 1.0 1.1 Dieckmann, KP.; Wilken, S.; Loy, V.; Matthies, C.; Kleinschmidt, K.; Bedke, J.; Martinschek, A.; Souchon, R. et al. (May 2013). "Treatment of testicular intraepithelial neoplasia (intratubular germ cell neoplasia unspecified) with local radiotherapy or with platinum-based chemotherapy: a survey of the German Testicular Cancer Study Group.". Ann Oncol 24 (5): 1332-7. doi:10.1093/annonc/mds628. PMID 23293116.
  2. ↑ Berney, DM.; Looijenga, L.; Idrees, M.; Oosterhuis, JW.; Rajpert-De Meyts, E.; Ulbright, TM.; Skakkebaek, NE. (Feb 2016). "Germ Cell Neoplasia In Situ (GCNIS). Evolution of the Current Nomenclature for Testicular Pre-invasive Germ Cell Malignancy.". Histopathology. doi:10.1111/his.12958. PMID 26918959.
  3. ↑ Müller J, Skakkebaek NE, Parkinson MC (February 1987). "The spermatocytic seminoma: views on pathogenesis". Int. J. Androl. 10 (1): 147–56. PMID 3583416.
  4. ↑ Manivel JC, Simonton S, Wold LE, Dehner LP (June 1988). "Absence of intratubular germ cell neoplasia in testicular yolk sac tumors in children. A histochemical and immunohistochemical study". Arch. Pathol. Lab. Med. 112 (6): 641–5. PMID 2837162.
  5. ↑ 5.0 5.1 5.2 Rakheja, D.; Hoang, MP.; Sharma, S.; Albores-Saavedra, J. (Apr 2002). "Intratubular embryonal carcinoma.". Arch Pathol Lab Med 126 (4): 487-90. doi:10.1043/0003-9985(2002)1260487:IEC2.0.CO;2. PMID 11900581. http://www.archivesofpathology.org/doi/full/10.1043/0003-9985(2002)126%3C0487:IEC%3E2.0.CO;2.
  6. ↑ Lau, SK.; Weiss, LM.; Chu, PG. (Jul 2007). "Association of intratubular seminoma and intratubular embryonal carcinoma with invasive testicular germ cell tumors.". Am J Surg Pathol 31 (7): 1045-9. doi:10.1097/PAS.0b013e31802b8712. PMID 17592271.
  7. ↑ URL: http://www.webpathology.com/image.asp?case=30&n=1. Accessed on: 18 May 2010.
  8. ↑ Gondos, B.; Migliozzi, JA. (Nov 1987). "Intratubular germ cell neoplasia.". Semin Diagn Pathol 4 (4): 292-303. PMID 3328244.
  9. ↑ URL: http://www.webpathology.com/image.asp?n=3&Case=28. Accessed on: 25 March 2013.
  10. ↑ Amin, MB.; Epstein, JI.; Ulbright, TM.; Humphrey, PA.; Egevad, L.; Montironi, R.; Grignon, D.; Trpkov, K. et al. (Aug 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.
  11. ↑ Schreiber, L.; Lifschitz-Mercer, B.; Paz, G.; Yavetz, H.; Elliott, DJ.; Kula, K.; Slowikowska-Hilczer, J.; Maymon, BB. (Jan 2003). "Double immunolabeling by the RBM and the PLAP markers for identifying intratubular (in situ) germ cell neoplasia of the testis.". Int J Surg Pathol 11 (1): 17-20. PMID 12598912.
  12. ↑ Biermann, K.; Stoop, H.; Looijenga, L. (May 2012). "c-KIT protein expression does not discriminate neoplastic from non-neoplastic intratubular germ cells.". Histopathology 60 (6): 1017-9. doi:10.1111/j.1365-2559.2011.04157.x. PMID 22340755.
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