Difference between revisions of "Germ cell neoplasia in situ"

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Germ cell neoplasia in situ (view source)

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#redirect [[Testis#Intratubular_germ_cell_neoplasia]]
{{ 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==
*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:
*[[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>
*Teratoma.{{Fact}}
 
Classification:<ref name=pmid11900581/>
*Undifferentiated GCNIS.
*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 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==
Features:<ref>URL: [http://www.webpathology.com/image.asp?case=30&n=1 http://www.webpathology.com/image.asp?case=30&n=1]. Accessed on: 18 May 2010.</ref><ref name=pmid3328244>{{Cite journal  | last1 = Gondos | first1 = B. | last2 = Migliozzi | first2 = JA. | title = Intratubular germ cell neoplasia. | journal = Semin Diagn Pathol | volume = 4 | issue = 4 | pages = 292-303 | month = Nov | year = 1987 | doi =  | PMID = 3328244 }}</ref>
*"Large" round ''or'' polygonal nuclei.
**Size in relation to normal often not defined.
***Rakheja ''et al.'' say >= 5x a lymphocyte for intratubular embryonal carcinoma.<ref name=pmid11900581>{{Cite journal  | last1 = Rakheja | first1 = D. | last2 = Hoang | first2 = MP. | last3 = Sharma | first3 = S. | last4 = Albores-Saavedra | first4 = J. | title = Intratubular embryonal carcinoma. | journal = Arch Pathol Lab Med | volume = 126 | issue = 4 | pages = 487-90 | month = Apr | year = 2002 | doi = 10.1043/0003-9985(2002)1260487:IEC2.0.CO;2 | PMID = 11900581 | url = http://www.archivesofpathology.org/doi/full/10.1043/0003-9985(2002)126%3C0487:IEC%3E2.0.CO;2 }}</ref>
**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.{{fact}}
 
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>
*[[Seminoma]] - especially intratubular predominant growth pattern.
*[[Embryonal carcinoma]].
*[[Mixed germ cell tumour]].
 
===Images===
====Case 1====
<gallery>
Image: Intratubular germ cell neoplasia - intermed mag.jpg | GCNIS (ITGCN) - intermed. mag.
Image: Intratubular germ cell neoplasia - high mag.jpg | GCNIS (ITGCN) - 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 | GCNIS (ITGCN) - very high mag.
</gallery>
====Case 2====
<gallery>
Image:Intratubular_germ_cell_neoplasia_high_mag_cropped.jpg | GCNIS (ITGCN) - cropped. (WC/Nephron)
Image:Intratubular_germ_cell_neoplasia_high_mag.jpg | GCNIS (ITGCN). (WC/Nephron)
</gallery>
====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.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==
===ISUP consensus===
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.
**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.
 
==See also==
*[[Testis]].
*[[Germ cell tumours]].
 
==References==
{{Reflist|2}}


[[Category:Diagnosis]]
[[Category:Diagnosis]]
[[Category:Testis]]
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