Testicular cancer pathophysiology: Difference between revisions

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{{CMG}}; {{AE}} {{G.D.}}, {{SC}}
{{CMG}}; {{AE}} {{G.D.}}, {{SC}}
==Overview==
==Overview==
The pathophysiology of testicular cancer depends on the histological cell subtypes and findings. Most testicular cancers derived from the lack of differentiation of primordial germ cell into spermatogonia.  
The [[pathophysiology]] of testicular cancer depends on the [[histological]] cell subtypes and findings. Most testicular cancers derived from the lack of differentiation of [[Primordial germ cells|primordial]] [[germ cell]] into [[spermatogonia]]. [[Germ cells]] testicular tumor have some [[genetic]] component while most sex [[Stromal|cord stromal]] testicular cancer are [[hormonal]] dependent. Most gross [[pathology]] of testicular tumors look similar on the physical appearance. On [[microscopic]] [[histopathological]] analysis of testicular cancer, fried-egg appearance is the characteristic finding of [[seminoma]]; marked [[nuclear]] [[atypia]] is the characteristic finding of [[embryonal carcinoma]]; hyaline-type globules, and Schiller-Duval bodies are characteristic findings of [[yolk sac tumor ]] ; syncytiotrophoblasts and [[cytotrophoblast]] cells are the characteristic findings of [[choriocarcinoma]], [[Polymorphism]] with"spirene" [[chromatin]] for spermatocytic.
On microscopic histopathological analysis of testicular cancer, fried-egg appearance is the characteristic finding of [[seminoma]]; marked nuclear atypia is the characteristic finding of [[embryonal carcinoma]]; blander cytomorphology, hyaline-type globules, and Schiller-Duval bodies are characteristic findings of [[yolk sac tumor ]] ; syncytiotrophoblasts and cytotrophoblast cells are the characteristic findings of [[choriocarcinoma]].


==Pathogenesis==
==Pathogenesis==
==Normal process==
===Normal process of testicular germ cells===
* Normal inner cell mass leads to primordial germ cell mass<ref name="MiyaiIto2019">{{cite journal|last1=Miyai|first1=Kosuke|last2=Ito|first2=Keiichi|last3=Nakanishi|first3=Kuniaki|last4=Tsuda|first4=Hitoshi|title=Seminoma component of mixed testicular germ cell tumor shows a higher incidence of loss of heterozygosity than pure-type seminoma|journal=Human Pathology|volume=84|year=2019|pages=71–80|issn=00468177|doi=10.1016/j.humpath.2018.09.007}}</ref><ref name="pmid23575763">{{cite journal |vauthors=Kraggerud SM, Hoei-Hansen CE, Alagaratnam S, Skotheim RI, Abeler VM, Rajpert-De Meyts E, Lothe RA |title=Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: implications for pathogenesis |journal=Endocr. Rev. |volume=34 |issue=3 |pages=339–76 |date=June 2013 |pmid=23575763 |pmc=3787935 |doi=10.1210/er.2012-1045 |url=}}</ref>
* Normal inner [[cell]] [[mass]] leads to primordial [[Germ cells|germ cell]] [[mass]]<ref name="MiyaiIto2019">{{cite journal|last1=Miyai|first1=Kosuke|last2=Ito|first2=Keiichi|last3=Nakanishi|first3=Kuniaki|last4=Tsuda|first4=Hitoshi|title=Seminoma component of mixed testicular germ cell tumor shows a higher incidence of loss of heterozygosity than pure-type seminoma|journal=Human Pathology|volume=84|year=2019|pages=71–80|issn=00468177|doi=10.1016/j.humpath.2018.09.007}}</ref><ref name="pmid23575763">{{cite journal |vauthors=Kraggerud SM, Hoei-Hansen CE, Alagaratnam S, Skotheim RI, Abeler VM, Rajpert-De Meyts E, Lothe RA |title=Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: implications for pathogenesis |journal=Endocr. Rev. |volume=34 |issue=3 |pages=339–76 |date=June 2013 |pmid=23575763 |pmc=3787935 |doi=10.1210/er.2012-1045 |url=}}</ref>


* Primordial germ cell mass leads to gonocytes through cell proliferation
* [[Primordial germ cells|Primordial]] [[germ cell]] [[mass]] leads to [[Gonocyte|gonocytes]] through [[cell]] proliferation
* Gonocytes differentiate into spermatogonia
* [[Gonocyte|Gonocytes]] differentiate into [[spermatogonia]]
=Germ cells tumors=
===Normal process of testicular sex cord stromal===
==Germ cell tumors derived from germ cell neoplasia in situ==
====Leydig cells====
* Lack of primordial germ cell to differentiate into spermatogonia leads to germ cell neoplasia in Situ<ref name="pmid23575763">{{cite journal |vauthors=Kraggerud SM, Hoei-Hansen CE, Alagaratnam S, Skotheim RI, Abeler VM, Rajpert-De Meyts E, Lothe RA |title=Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: implications for pathogenesis |journal=Endocr. Rev. |volume=34 |issue=3 |pages=339–76 |date=June 2013 |pmid=23575763 |pmc=3787935 |doi=10.1210/er.2012-1045 |url=}}</ref>
*[[Leydig cells]] are found in the [[seminiferous tubules]] of the [[testis]].<ref name="pmid17284120">{{cite journal |vauthors=Al-Agha OM, Axiotis CA |title=An in-depth look at Leydig cell tumor of the testis |journal=Arch. Pathol. Lab. Med. |volume=131 |issue=2 |pages=311–7 |date=February 2007 |pmid=17284120 |doi=10.1043/1543-2165(2007)131[311:AILALC]2.0.CO;2 |url=}}</ref><ref name="pmid1095296">{{cite journal |vauthors=Neaves WB |title=Leydig cells |journal=Contraception |volume=11 |issue=5 |pages=571–606 |date=May 1975 |pmid=1095296 |doi= |url=}}</ref>
* Germ cell neoplasia in Situ may gain some abnormal chromosome(12), then it leads to seminomas and nonseminomas cancers.
*[[Leydig cells]] secrete [[testosterone]] [[hormone]] under the signal of [[luteinizing hormone]].
*Seminomas and non seminotous germ cell tumors have similar pathogenesis<ref name="pmid16614105">{{cite journal |vauthors=Bray F, Richiardi L, Ekbom A, Forman D, Pukkala E, Cuninkova M, Møller H |title=Do testicular seminoma and nonseminoma share the same etiology? Evidence from an age-period-cohort analysis of incidence trends in eight European countries |journal=Cancer Epidemiol. Biomarkers Prev. |volume=15 |issue=4 |pages=652–8 |date=April 2006 |pmid=16614105 |doi=10.1158/1055-9965.EPI-05-0565 |url=}}</ref><ref name="pmid15821489">{{cite journal |vauthors=Linke J, Loy V, Dieckmann KP |title=Prevalence of testicular intraepithelial neoplasia in healthy males |journal=J. Urol. |volume=173 |issue=5 |pages=1577–9 |date=May 2005 |pmid=15821489 |doi=10.1097/01.ju.0000154348.68575.95 |url=}}</ref>
*[[Leydig cells]] are involved in the [[Development|developmen]]<nowiki/>t of [[male]] [[secondary sexual characteristics]] and [[spermatogenesis]].  
*Aneuploid
==Germ cells tumors==
*Loss of chromosomes 4,5,11,13,18, and Y
===Germ cell tumors derived from germ cell neoplasia in situ===
*Gain of chromosomes 7,8,12, and X
* Lack of [[Primordial germ cells|primordial germ cell]] to differentiate into [[spermatogonia]] leads to [[Germ cell neoplasm|germ cell neoplasia]] in Situ<ref name="pmid23575763">{{cite journal |vauthors=Kraggerud SM, Hoei-Hansen CE, Alagaratnam S, Skotheim RI, Abeler VM, Rajpert-De Meyts E, Lothe RA |title=Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: implications for pathogenesis |journal=Endocr. Rev. |volume=34 |issue=3 |pages=339–76 |date=June 2013 |pmid=23575763 |pmc=3787935 |doi=10.1210/er.2012-1045 |url=}}</ref>
* More than 90% of all testicular cancers are [[germ cell tumors]]. This type of cancer starts in germ cells, which are the cells that develop into [[sperm]]s.
* [[Germ cell]] [[neoplasia]] in Situ may gain some abnormal [[chromosome]](12), then it leads to [[Seminoma|seminomas]] and [[Nonseminoma|nonseminomas cancers]].
* About 50% of all germ cell tumors are seminomas, or seminomatous germ cell tumours. They grow slower than non-seminomas.
*[[Seminoma|Seminomas]] and [[Germ cell tumors|non seminotous germ cell tumors]] have similar [[pathogenesis]].<ref name="pmid16614105">{{cite journal |vauthors=Bray F, Richiardi L, Ekbom A, Forman D, Pukkala E, Cuninkova M, Møller H |title=Do testicular seminoma and nonseminoma share the same etiology? Evidence from an age-period-cohort analysis of incidence trends in eight European countries |journal=Cancer Epidemiol. Biomarkers Prev. |volume=15 |issue=4 |pages=652–8 |date=April 2006 |pmid=16614105 |doi=10.1158/1055-9965.EPI-05-0565 |url=}}</ref><ref name="pmid15821489">{{cite journal |vauthors=Linke J, Loy V, Dieckmann KP |title=Prevalence of testicular intraepithelial neoplasia in healthy males |journal=J. Urol. |volume=173 |issue=5 |pages=1577–9 |date=May 2005 |pmid=15821489 |doi=10.1097/01.ju.0000154348.68575.95 |url=}}</ref>
* Overrepresentation of short arm of chromosomes 12p may be related to invasive growth of seminomas and nonseminomatous testicular cancer.<ref name="pmid11127816">{{cite journal |vauthors=Rosenberg C, Van Gurp RJ, Geelen E, Oosterhuis JW, Looijenga LH |title=Overrepresentation of the short arm of chromosome 12 is related to invasive growth of human testicular seminomas and nonseminomas |journal=Oncogene |volume=19 |issue=51 |pages=5858–62 |date=November 2000 |pmid=11127816 |doi= |url=}}</ref>
**[[Aneuploid]]
* Seminomas tumors may have both genetic and immune components due to lymphocytes infiltration in HIV patients.<ref name="pmid12743144">{{cite journal |vauthors=Powles T, Bower M, Daugaard G, Shamash J, De Ruiter A, Johnson M, Fisher M, Anderson J, Mandalia S, Stebbing J, Nelson M, Gazzard B, Oliver T |title=Multicenter study of human immunodeficiency virus-related germ cell tumors |journal=J. Clin. Oncol. |volume=21 |issue=10 |pages=1922–7 |date=May 2003 |pmid=12743144 |doi=10.1200/JCO.2003.09.107 |url=}}</ref>
**Loss of [[chromosomes]] 4,5,11,13,18, and Y
* Histological of seminomas tumor in HIV patients: tumor infiltrated by lymphocytes which may lead to weak immune system response.<ref name="pmid12743144">{{cite journal |vauthors=Powles T, Bower M, Daugaard G, Shamash J, De Ruiter A, Johnson M, Fisher M, Anderson J, Mandalia S, Stebbing J, Nelson M, Gazzard B, Oliver T |title=Multicenter study of human immunodeficiency virus-related germ cell tumors |journal=J. Clin. Oncol. |volume=21 |issue=10 |pages=1922–7 |date=May 2003 |pmid=12743144 |doi=10.1200/JCO.2003.09.107 |url=}}</ref>
**Gain of [[chromosomes]] 7,8,12, and X
* familial contribution:<ref name="RapleyCrockford2000">{{cite journal|last1=Rapley|first1=Elizabeth A.|last2=Crockford|first2=Gillian P.|last3=Teare|first3=Dawn|last4=Biggs|first4=Patrick|last5=Seal|first5=Sheila|last6=Barfoot|first6=Rita|last7=Edwards|first7=Sandra|last8=Hamoudi|first8=Rifat|last9=Heimdal|first9=Ketil|last10=Fosså|first10=Sophie D.|last11=Tucker|first11=Kathy|last12=Donald|first12=Jenny|last13=Collins|first13=Felicity|last14=Friedlander|first14=Michael|last15=Hogg|first15=David|last16=Goss|first16=Paul|last17=Heidenreich|first17=Axel|last18=Ormiston|first18=Wilma|last19=Daly|first19=Peter A.|last20=Forman|first20=David|last21=Oliver|first21=Timothy D.|last22=Leahy|first22=Michael|last23=Huddart|first23=Robert|last24=Cooper|first24=Colin S.|last25=Bodmer|first25=Julia G.|last26=Easton|first26=Douglas F.|last27=Stratton|first27=Michael R.|last28=Bishop|first28=D. Timothy|title=Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours|journal=Nature Genetics|volume=24|issue=2|year=2000|pages=197–200|issn=1061-4036|doi=10.1038/72877}}</ref>
* More than 90% of all testicular cancers are [[germ cell tumors]]. This type of [[cancer]] starts in [[germ cells]], which are the [[cells]] that develop into [[sperm]]s.
**Gene on chromosome Xq27 may be related to testicular germ cell tumors
* About 50% of all [[germ cell tumors]] are [[Seminoma|seminomas]], or [[seminomatous germ cell tumours]]. They grow slower than [[Nonseminoma|non-seminomas]].
* Some proteins such as C-kit (receptor) and placental-like alkaline phosphatase (PLAP) may be excessively expressed<ref name="pmid15821122">{{cite journal |vauthors=Hoei-Hansen CE, Rajpert-De Meyts E, Daugaard G, Skakkebaek NE |title=Carcinoma in situ testis, the progenitor of testicular germ cell tumours: a clinical review |journal=Ann. Oncol. |volume=16 |issue=6 |pages=863–8 |date=June 2005 |pmid=15821122 |doi=10.1093/annonc/mdi175 |url=}}</ref>
* Overrepresentation of short arm of [[Chromosome|chromosomes]] 12p may be related to invasive growth of [[Seminoma|seminomas]] and nonseminomatous testicular cancer.<ref name="pmid11127816">{{cite journal |vauthors=Rosenberg C, Van Gurp RJ, Geelen E, Oosterhuis JW, Looijenga LH |title=Overrepresentation of the short arm of chromosome 12 is related to invasive growth of human testicular seminomas and nonseminomas |journal=Oncogene |volume=19 |issue=51 |pages=5858–62 |date=November 2000 |pmid=11127816 |doi= |url=}}</ref>
==Germ cell tumors unrelated to germ cell neoplasia in situ==
* Seminomas tumors may have both [[genetic]] and [[immune]] components due to [[lymphocytes]] infiltration in [[HIV]] patients.<ref name="pmid12743144">{{cite journal |vauthors=Powles T, Bower M, Daugaard G, Shamash J, De Ruiter A, Johnson M, Fisher M, Anderson J, Mandalia S, Stebbing J, Nelson M, Gazzard B, Oliver T |title=Multicenter study of human immunodeficiency virus-related germ cell tumors |journal=J. Clin. Oncol. |volume=21 |issue=10 |pages=1922–7 |date=May 2003 |pmid=12743144 |doi=10.1200/JCO.2003.09.107 |url=}}</ref>
*Mutations from the proteins that may be involved in the maturation of the spermatogonia.<ref name="pmid21725972">{{cite journal |vauthors=Looijenga LH |title=Spermatocytic seminoma: toward further understanding of pathogenesis |journal=J. Pathol. |volume=224 |issue=4 |pages=431–3 |date=August 2011 |pmid=21725972 |doi=10.1002/path.2939 |url=}}</ref>
* [[Histological]] of seminomas tumor in [[HIV]] [[patients]]: [[tumor]] infiltrated by [[lymphocytes]] which may lead to weak [[immune]] [[System|system response]].<ref name="pmid12743144">{{cite journal |vauthors=Powles T, Bower M, Daugaard G, Shamash J, De Ruiter A, Johnson M, Fisher M, Anderson J, Mandalia S, Stebbing J, Nelson M, Gazzard B, Oliver T |title=Multicenter study of human immunodeficiency virus-related germ cell tumors |journal=J. Clin. Oncol. |volume=21 |issue=10 |pages=1922–7 |date=May 2003 |pmid=12743144 |doi=10.1200/JCO.2003.09.107 |url=}}</ref>
*Mostly located in the testis and rarely metastases
* [[Familial]] contribution:<ref name="RapleyCrockford2000">{{cite journal|last1=Rapley|first1=Elizabeth A.|last2=Crockford|first2=Gillian P.|last3=Teare|first3=Dawn|last4=Biggs|first4=Patrick|last5=Seal|first5=Sheila|last6=Barfoot|first6=Rita|last7=Edwards|first7=Sandra|last8=Hamoudi|first8=Rifat|last9=Heimdal|first9=Ketil|last10=Fosså|first10=Sophie D.|last11=Tucker|first11=Kathy|last12=Donald|first12=Jenny|last13=Collins|first13=Felicity|last14=Friedlander|first14=Michael|last15=Hogg|first15=David|last16=Goss|first16=Paul|last17=Heidenreich|first17=Axel|last18=Ormiston|first18=Wilma|last19=Daly|first19=Peter A.|last20=Forman|first20=David|last21=Oliver|first21=Timothy D.|last22=Leahy|first22=Michael|last23=Huddart|first23=Robert|last24=Cooper|first24=Colin S.|last25=Bodmer|first25=Julia G.|last26=Easton|first26=Douglas F.|last27=Stratton|first27=Michael R.|last28=Bishop|first28=D. Timothy|title=Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours|journal=Nature Genetics|volume=24|issue=2|year=2000|pages=197–200|issn=1061-4036|doi=10.1038/72877}}</ref>
*Mutated proteins invovloved:SAGE1 and SSX2-4
**[[Gene]] on [[chromosome]] Xq27 may be related to testicular [[germ cell tumors]]
*Hypothesis of gain of chromosome 9 may be involved in the process<ref name="pmid26612222">{{cite journal |vauthors=Howitt BE, Berney DM |title=Tumors of the Testis: Morphologic Features and Molecular Alterations |journal=Surg Pathol Clin |volume=8 |issue=4 |pages=687–716 |date=December 2015 |pmid=26612222 |doi=10.1016/j.path.2015.07.007 |url=}}</ref>
* Some [[proteins]] such as [[C-kit]] (receptor) and placental-like alkaline phosphatase (PLAP) may be excessively expressed<ref name="pmid15821122">{{cite journal |vauthors=Hoei-Hansen CE, Rajpert-De Meyts E, Daugaard G, Skakkebaek NE |title=Carcinoma in situ testis, the progenitor of testicular germ cell tumours: a clinical review |journal=Ann. Oncol. |volume=16 |issue=6 |pages=863–8 |date=June 2005 |pmid=15821122 |doi=10.1093/annonc/mdi175 |url=}}</ref>
===Germ cell tumors unrelated to germ cell neoplasia in situ===
*[[Mutations]] from the [[proteins]] that may be involved in the [[maturation]] of the [[spermatogonia]].<ref name="pmid21725972">{{cite journal |vauthors=Looijenga LH |title=Spermatocytic seminoma: toward further understanding of pathogenesis |journal=J. Pathol. |volume=224 |issue=4 |pages=431–3 |date=August 2011 |pmid=21725972 |doi=10.1002/path.2939 |url=}}</ref>
*Mostly located in the [[testis]] and rarely [[metastases]].
*[[Mutated]] [[proteins]] involved: SAGE1 and SSX2-4.
*Hypothesis of gain of [[chromosome]] 9 may be involved in the process.<ref name="pmid26612222">{{cite journal |vauthors=Howitt BE, Berney DM |title=Tumors of the Testis: Morphologic Features and Molecular Alterations |journal=Surg Pathol Clin |volume=8 |issue=4 |pages=687–716 |date=December 2015 |pmid=26612222 |doi=10.1016/j.path.2015.07.007 |url=}}</ref>


==Testicular sex cord stromal tumors==
===Leydig cells tumor===
*The [[pathogenesis]] of [[leydig cells]] tumors is not well understood.<ref name="pmid17284120">{{cite journal |vauthors=Al-Agha OM, Axiotis CA |title=An in-depth look at Leydig cell tumor of the testis |journal=Arch. Pathol. Lab. Med. |volume=131 |issue=2 |pages=311–7 |date=February 2007 |pmid=17284120 |doi=10.1043/1543-2165(2007)131[311:AILALC]2.0.CO;2 |url=}}</ref><ref name="pmid16097561">{{cite journal |vauthors=Conkey DS, Howard GC, Grigor KM, McLaren DB, Kerr GR |title=Testicular sex cord-stromal tumours: the Edinburgh experience 1988-2002, and a review of the literature |journal=Clin Oncol (R Coll Radiol) |volume=17 |issue=5 |pages=322–7 |date=August 2005 |pmid=16097561 |doi= |url=}}</ref>
*It is hypothesized that there is a disturbance of hypothalamic-pituitary-testicular axis which lead to excess of [[hormone]] productions.
*The [[G proteins]] in the [[leydig cells]] and the structure alteration of [[Luteinizing hormone]] receptors may play role in [[leydig cells]] tumors.
===Sertoli cell tumor===
*[[Sertoli cell]] arise from [[testicular]] supporting cells which regulate the [[spermatogenesis]].
*It may due to excess production of [[androgen]] [[hormone]].<ref name="DilworthFarrow1991">{{cite journal|last1=Dilworth|first1=J. Patrick|last2=Farrow|first2=George M.|last3=Oesterling|first3=Joseph E.|title=Non-germ cell tumors of testis|journal=Urology|volume=37|issue=5|year=1991|pages=399–417|issn=00904295|doi=10.1016/0090-4295(91)80100-L}}</ref>
===Granulosa cell tumor===
* It involved in [[hyperestrogenism]] due to an unregulated [[aromatase]] [[enzyme]] activity that leads to excessive production of [[hormones]].<ref name="pmid8406422">{{cite journal |vauthors=Jimenez-Quintero LP, Ro JY, Zavala-Pompa A, Amin MB, Tetu B, Ordoñez NG, Ayala AG |title=Granulosa cell tumor of the adult testis: a clinicopathologic study of seven cases and a review of the literature |journal=Hum. Pathol. |volume=24 |issue=10 |pages=1120–5 |date=October 1993 |pmid=8406422 |doi= |url=}}</ref>
==Gross and Microscopic Pathology==
==Gross and Microscopic Pathology==
The gross and microscopic features of the most common tumors are described below:<ref name="pmid292626682">{{cite journal |vauthors=Boccellino M, Vanacore D, Zappavigna S, Cavaliere C, Rossetti S, D'Aniello C, Chieffi P, Amler E, Buonerba C, Di Lorenzo G, Di Franco R, Izzo A, Piscitelli R, Iovane G, Muto P, Botti G, Perdonà S, Caraglia M, Facchini G |title=Testicular cancer from diagnosis to epigenetic factors |journal=Oncotarget |volume=8 |issue=61 |pages=104654–104663 |date=November 2017 |pmid=29262668 |pmc=5732834 |doi=10.18632/oncotarget.20992 |url=}}</ref><ref name="pmid266122222">{{cite journal |vauthors=Howitt BE, Berney DM |title=Tumors of the Testis: Morphologic Features and Molecular Alterations |journal=Surg Pathol Clin |volume=8 |issue=4 |pages=687–716 |date=December 2015 |pmid=26612222 |doi=10.1016/j.path.2015.07.007 |url=}}</ref><ref name="pmid26742998">{{cite journal |vauthors=Siegel RL, Miller KD, Jemal A |title=Cancer statistics, 2016 |journal=CA Cancer J Clin |volume=66 |issue=1 |pages=7–30 |date=2016 |pmid=26742998 |doi=10.3322/caac.21332 |url=}}</ref>
The [[gross]] and [[microscopic]] features of the most common [[tumors]] are described below:<ref name="pmid292626682">{{cite journal |vauthors=Boccellino M, Vanacore D, Zappavigna S, Cavaliere C, Rossetti S, D'Aniello C, Chieffi P, Amler E, Buonerba C, Di Lorenzo G, Di Franco R, Izzo A, Piscitelli R, Iovane G, Muto P, Botti G, Perdonà S, Caraglia M, Facchini G |title=Testicular cancer from diagnosis to epigenetic factors |journal=Oncotarget |volume=8 |issue=61 |pages=104654–104663 |date=November 2017 |pmid=29262668 |pmc=5732834 |doi=10.18632/oncotarget.20992 |url=}}</ref><ref name="pmid266122222">{{cite journal |vauthors=Howitt BE, Berney DM |title=Tumors of the Testis: Morphologic Features and Molecular Alterations |journal=Surg Pathol Clin |volume=8 |issue=4 |pages=687–716 |date=December 2015 |pmid=26612222 |doi=10.1016/j.path.2015.07.007 |url=}}</ref><ref name="pmid26742998">{{cite journal |vauthors=Siegel RL, Miller KD, Jemal A |title=Cancer statistics, 2016 |journal=CA Cancer J Clin |volume=66 |issue=1 |pages=7–30 |date=2016 |pmid=26742998 |doi=10.3322/caac.21332 |url=}}</ref><ref name="pmid6093440">{{cite journal| author=Krag Jacobsen G, Barlebo H, Olsen J, Schultz HP, Starklint H, Søgaard H et al.| title=Testicular germ cell tumours in Denmark 1976-1980. Pathology of 1058 consecutive cases. | journal=Acta Radiol Oncol | year= 1984 | volume= 23 | issue= 4 | pages= 239-47 | pmid=6093440 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6093440  }} </ref><ref name="pmid23478232">{{cite journal |vauthors=Emerson RE, Cheng L |title=Premalignancy of the testis and paratestis |journal=Pathology |volume=45 |issue=3 |pages=264–72 |date=April 2013 |pmid=23478232 |doi=10.1097/PAT.0b013e32835f3e1a |url=}}</ref><ref name="pmid29262668">{{cite journal |vauthors=Boccellino M, Vanacore D, Zappavigna S, Cavaliere C, Rossetti S, D'Aniello C, Chieffi P, Amler E, Buonerba C, Di Lorenzo G, Di Franco R, Izzo A, Piscitelli R, Iovane G, Muto P, Botti G, Perdonà S, Caraglia M, Facchini G |title=Testicular cancer from diagnosis to epigenetic factors |journal=Oncotarget |volume=8 |issue=61 |pages=104654–104663 |date=November 2017 |pmid=29262668 |pmc=5732834 |doi=10.18632/oncotarget.20992 |url=}}</ref><ref name="pmid6155988">{{cite journal| author=Talerman A, Haije WG, Baggerman L| title=Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: correlation between endodermal sinus (yolk sac) tumor and raised serum AFP. | journal=Cancer | year= 1980 | volume= 46 | issue= 2 | pages= 380-5 | pmid=6155988 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6155988  }} </ref><ref name="pmid6093440">{{cite journal| author=Krag Jacobsen G, Barlebo H, Olsen J, Schultz HP, Starklint H, Søgaard H et al.| title=Testicular germ cell tumours in Denmark 1976-1980. Pathology of 1058 consecutive cases. | journal=Acta Radiol Oncol | year= 1984 | volume= 23 | issue= 4 | pages= 239-47 | pmid=6093440 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6093440  }} </ref><ref name="pmid8583612">{{cite journal |vauthors=Simmonds PD, Lee AH, Theaker JM, Tung K, Smart CJ, Mead GM |title=Primary pure teratoma of the testis |journal=J. Urol. |volume=155 |issue=3 |pages=939–42 |date=March 1996 |pmid=8583612 |doi= |url=}}</ref><ref name="pmid10375083">{{cite journal |vauthors=Shahab N, Doll DC |title=Testicular lymphoma |journal=Semin. Oncol. |volume=26 |issue=3 |pages=259–69 |date=June 1999 |pmid=10375083 |doi= |url=}}</ref><ref name="pmid20331874">{{cite journal |vauthors=Chuang KL, Liaw CC, Ueng SH, Liao SK, Pang ST, Chang YH, Chuang HC, Chuang CK |title=Mixed germ cell tumor metastatic to the skin: case report and literature review |journal=World J Surg Oncol |volume=8 |issue= |pages=21 |date=March 2010 |pmid=20331874 |pmc=2851696 |doi=10.1186/1477-7819-8-21 |url=}}</ref><ref name="pmid3820391">{{cite journal |vauthors=Ramón y Cajal S, Piñango L, Barat A, Moldenhauer F, Oliva H |title=Metastatic pure choriocarcinoma of the testis in an elderly man |journal=J. Urol. |volume=137 |issue=3 |pages=516–9 |date=March 1987 |pmid=3820391 |doi= |url=}}</ref><ref name="pmid25547829">{{cite journal |vauthors=Wei Y, Wu S, Lin T, He D, Li X, Liu J, Liu X, Hua Y, Lu P, Wei G |title=Testicular yolk sac tumors in children: a review of 61 patients over 19 years |journal=World J Surg Oncol |volume=12 |issue= |pages=400 |date=December 2014 |pmid=25547829 |pmc=4326497 |doi=10.1186/1477-7819-12-400 |url=}}</ref><ref name="pmid17284120">{{cite journal |vauthors=Al-Agha OM, Axiotis CA |title=An in-depth look at Leydig cell tumor of the testis |journal=Arch. Pathol. Lab. Med. |volume=131 |issue=2 |pages=311–7 |date=February 2007 |pmid=17284120 |doi=10.1043/1543-2165(2007)131[311:AILALC]2.0.CO;2 |url=}}</ref><ref name="pmid9808128">{{cite journal |vauthors=Cheville JC, Sebo TJ, Lager DJ, Bostwick DG, Farrow GM |title=Leydig cell tumor of the testis: a clinicopathologic, DNA content, and MIB-1 comparison of nonmetastasizing and metastasizing tumors |journal=Am. J. Surg. Pathol. |volume=22 |issue=11 |pages=1361–7 |date=November 1998 |pmid=9808128 |doi= |url=}}</ref><ref name="pmid15502809">{{cite journal |vauthors=Young RH |title=Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems |journal=Mod. Pathol. |volume=18 Suppl 2 |issue= |pages=S81–98 |date=February 2005 |pmid=15502809 |doi=10.1038/modpathol.3800311 |url=}}</ref><ref name="pmid8406422">{{cite journal |vauthors=Jimenez-Quintero LP, Ro JY, Zavala-Pompa A, Amin MB, Tetu B, Ordoñez NG, Ayala AG |title=Granulosa cell tumor of the adult testis: a clinicopathologic study of seven cases and a review of the literature |journal=Hum. Pathol. |volume=24 |issue=10 |pages=1120–5 |date=October 1993 |pmid=8406422 |doi= |url=}}</ref>


{| class="wikitable"
{| class="wikitable"
Line 44: Line 59:
!Images
!Images
|-
|-
|Germ cell neoplasia in situ
![[Germ cell]] [[neoplasia]] [[in situ]]
|
|
* Solid, fleshy nodules
* [[Solid]], [[fleshy]] [[nodules]]
* Similar to seminoma in appearance
* Similar to [[seminoma]] in appearance
* Well-circumscribed with hemorraghic and necrotic areas
* Well-[[Circumscri|circumscribed]] with [[Hemorrag|hemorraghic]] and [[necrotic]] areas
|
* Hyperchromatic nuclei
*Prominent nucleoli and clear cytoplasm
*Thickened basement menbrane
*Proliferation of tumor germ cell in the seminiferous tubules
|
|
* [[Hyperchromatic]] [[nuclei]]
*Prominent [[nucleoli]] and clear [[cytoplasm]]
*[[Thickened]] basement menbrane
*Proliferation of [[tumor]] [[germ cell]] in the [[Seminiferous tubule|seminiferous tubules]]
| [[File:Intratubular germ cell neoplasia - 2 - very high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]]


|-
|-
|Seminoma
![[Seminoma]]
|
|
* Solid, firm without cross section
* [[Solid]], firm without cross section


* Solid fleshy tan to yellow mass in homogeneous appearance
* [[Solid]] fleshy tan to [[yellow]] [[mass]] in [[homogeneous]] appearance
* Well-circumscribed with small hemorraghic and necrotic areas
* Well-circumscribed with small [[hemorraghic]] and [[necrotic]] areas
|
* Large nucleoli with clear to pale to eosinophilic cytoplasma due to the presence of glycogen
* Clonal proliferation of neoplastic [[germ cells]]
* Fried-egg appearance
* Prominent mitotic figures
* Nests and sheets of cancer cells with "squared-off" nuclei
|
|
* Large [[nucleoli]] with clear to pale to [[eosinophilic]] [[cytoplasm]] due to the presence of [[glycogen]]
* [[Clonal]] proliferation of [[neoplastic]] [[germ cells]]
* [[Fried-egg]] appearance
* Prominent [[mitotic]] figures
* [[Nests]] and sheets of cancer cells with "squared-off" nuclei
* [[Granulomatous]] [[inflammation]]
| [[File:Intertubular seminoma -- intermed mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]]
|-
|-
|Embryonal carcinoma
![[Embryonal carcinoma]]
|
|
* They are usually solid and yellow
* Poorly demarcated [[mass]]
* [[Soft|Soft gray]] on cut surface
* Large hemorraghic and [[necrotic]] foci.
|
|
* They are characterized by simple and complex annular (ring-shaped) tubules often with calcification
* Presents with mixed [[histological]] features ([[solid]], papular, glandular)
* Marked [[Nuclear|nuclear atypia]]
* Marked [[epithelial cells]] with [[polymorphism]]
* Large [[nuclei]] with abundant [[amphophilic]] [[cytoplasm]]
* Prominent [[mitotic]] activities
|[[File:Embryonal carcinoma - high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]]


* They show tubules with Sertoli cells arranged around one or more hyaline bodies
|-
![[Yolk sac tumor]]
|
*[[Solid]], lobulated, soft, [[mucinous]] on cut  surface
*Gray and grayish [[yellow]] [[mass]]


* These tubules may be scattered and admixed with normal ovarian tissue rather than forming a distinct mass especially, in patients with Peutz-Jegher syndrome
*May have small hemorrhagic and [[necrotic]] foci
*[[Heterogenous]] [[mass]]
|
|
*Hyaline-type [[globules]]
* Schiller-Duval bodies
* Multiple [[histological]] patterns such as [[recticular]], [[microcystic]], [[glandular]], [[papillary]], hepatoid, and [[solid]]
* Associated with [[myxoid]] [[stroma]]
* Variable [[cytologic]] [[atypia]]
|[[File:Shiller Duval body.jpg|thumb|none|300px|Contributed by EDDAOUALLINE Hanane in wikimedia.commons]]


|-
|-
|Yolk sac tumor, postpubertal-type
![[Choriocarcinoma]]
|
|
*They are solid, lobulated, yellow on cut  surfaces
* Hemorrhagic and [[necrotic]] [[nodules]]
* May appear more [[cystic]] and calcified in [[homogeneous]]
|
* More Hemorrhagic and [[necrotic]]
* Made up of [[mononucleated]] [[trophoblast]] and [[multinucleated]] syncytiotrophoblast [[cells]]
* Hyperchomatic [[cytoplasm]]
|[[File:Choriocarcinoma - high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]]


*Retiform tumours have a spongy sectioned surface
|-
 
![[Teratoma]], postpubertal-type
*Poorly differentiated tumours may be extensively haemorrhagic and necrotic
|
|
*Well differentiated tumours are characterised by Sertoli cells in a predominantly tubular pattern, and Leydig cells in the intervening stroma
* Hetereogenous, [[cystic]] and irregular [[calcification]] on appearance
 
* [[Solid]], firm [[mass]]
*Tumours of intermediate differentiation often show a striking so-called alveolar pattern of Sertoli cells with pale cytoplasm
*Poorly differentiated tumors are usually dominantly sarcomatoid
 
*Retiform tumors shows elongated tubules and the stroma is focally somewhat hyalinised
*Heterologous elements include mucinous epithelial glands or rhabdomyosarcomatous and/or chondrosarcomatous elements
|
|
 
* Arrange in disorder fashion
* [[Cytological|Cytologic]] [[atypia]]
* High [[mitotic]] activities
* Presence of 3 [[germ]] [[cells]] layers
* Presence of [[immature]] elements with [[primitive]] [[nuclei]]
|[[File:Immature teratoma high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]]
|-
|-
|Choriocarcinoma
!Mixed [[germ cell tumors]]
|
|
* They are mostly solid masses with yellowish foci, edema, and cystic areas
* [[Solid]] and [[cystic]] [[mass]]
* More hemorhragic and [[necrotic]].
|
|
* A pseudolobular pattern, admixed spindled and rounded weakly luteinised cells,
*[[Microscopic]] findings are variable depending on the [[tumor]] type
 
*May have the component of [[yolk sac]] and [[choriocarcinoma]]
* Prominent typically ectatic branching staghorn-like blood vessels
|[[File:Mixed germ cell tumour - high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]]
|-
!Spermatocytic [[tumor]]
|
* Soft, gray, and gelatinous [[mass]]
* Well circumscribed with small hemorrhagic and [[necrotic]] foci.
|
|
* Atyical [[mitoses]] activities
* [[Eosinophilic]] [[cytoplasm]] without glycogen
* [[Tumors]] cells with three different sizes (small, intermediate, and large)
* [[Polymorphism]] with"spirene" [[chromatin]] find in the [[giant cells]]
*<nowiki/>Freque<nowiki/>nt [[apoptosis]]
|[[File:Spermatocytic seminoma high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]]
|-
![[Teratoma]], prepubertal-type,
[[Desmoid Tumor|Desmoid]] [[cyst]]


|-
[[Epidermoid cyst|Epidermoid]] [[cyst]]
|Teratoma, postpubertal-type
|
|
* They are bilateral with abnormal in appearance due to a  hypercerebriform contour
* [[Solid]] and firm [[mass]]
 
* often large masses  having a beefy appearance with oedema and cyst formation
|
|
* Microcytic change within the cellular neoplasm composed of admixed, spindled, and weakly luteinised cells
* Lack of cytologic [[atypia]]
* No [[mitotic]] activities
* Absence of immature elements
* [[Desmoid tumor|Desmoid]] cyst has polosebaceous cells
* [[Epidermoist]] cyst is surrounded with [[squamous]] [[epithelial cells]]
|[[File:Epidermoid cyst of testis -- high mag.jpg|thumb|none|100px|Contributed by Nephron in wikimedia.commons]]


* Normal ovarian elements are often present between the proliferating spindle cells
|
|-
|-
|Mixed germ cell tumors
![[Testicular]] [[lymphoma]]
|
|
* They are solid and cystic with solid tissue that is tan to white to rarely yellow.
* Soft, gray, and gelatinous [[mass]]
* Well circumscribed with small hemorrhagic and [[necrotic]] foci.
|
|
*The microscopic appearance consists of three components:
* Vascular invasion
* Microcysts (present in 60% of cases)
* [[Pleomorphic]] tumor cells
 
* Large irregular [[nuclei]]
* Solid cellular areas
|[[File:DLBCL of testis -- very high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]]
|-


* Hyalinised fibrous stroma
*The microcystic pattern is characterised by small round to oval cystic spaces, focally coalescing into larger irregular channels; intracytoplasmic vacuoles are also common
*The solid cellular areas are usually intersected by fibrous bands and hyalineplaques
|
|-
|-
|Spermatocytic tumor
![[Leydig cells|Leydig cells tumor]]
|
|
* They are solid ovarian tumors
* [[Homogeneous]] and well circumscribed [[mass]]
|
 
* Spindle-shaped [[fibroblast]]<nowiki/>s are seen
* [[Solitary]] and unilateral [[mass]]
* White to [[brown]] to yellow on cut surface
|
|
* [[Cells]] are arranged in nest, sheets polygonal fahsion
* [[Cytoplasm]] is [[eosinophilic]] with round [[nuclei]] and prominent [[nucleoli]]
* Presence of [[lipofuscin]] [[pigment]] and reinke [[crystal]] [[Intracytoplasmic sperm injection|intracytoplasmic]]
|[[File:Leydig cell tumour1.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]]
|-
|-
|Teratoma, prepubertal-type
![[Sertoli cell|Sertoli tumor]]
|
|
* They appear yellow on solid sectioned surface
* [[Homogeneous]] and well circumscribed [[mass]]
|
 
* Lipid-laden [[Stromal cell|stromal cells]] with pale, vaculolated [[cytoplasm]]
* White to grey on cut surface
*
|
|
* [[Cells]] are arranged in [[Cord|cords]], nests and lobulated [[tubules]]
* [[Fibrous]] [[stroma]] ans septa with [[lymphocytes]]
* Elongated spaces and microscysts
* Pale lipid- rich [[cytoplasm]]
* No prominent [[nucleoli]]
|[[File:Sertoli cell tumour high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]]
|-
|-
|Yolk sac tumor, prepubertal-type
 
![[Granulosa|Granulosa tumor]]
|
|
* They are large unilateral masses, often with necrosis and hemorrhage
Adult type
 
* No distint feature
Juvenile type
* [[Solid]], [[nodule]] yellow-orange and [[cystic]] [[mass]]
*
|
|
* Fibromas with increased cellularity and cell proliferation (''mitotic activity'')
Adult type
* [[Cells]] are arranged in elongated, microfollicular "call-Exner bodies"
Juvenile type
*[[Cells]] are presented in [[solid]] sheets and [[nodules]] and form the estatic space
*[[Eosinophilic]] [[cytoplasm]]
*Hyperchromatic, round to oval [[nuclei]]
*High [[mitotic]] activities
*[[Follicle|Follicles]] are located on the periphery
|[[File:Granulosa cell tumour2.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]]


* They follow a malignant course
|-
|
|}
|}
'''Germ cell Tumors'''<ref name="pmid6093440">{{cite journal| author=Krag Jacobsen G, Barlebo H, Olsen J, Schultz HP, Starklint H, Søgaard H et al.| title=Testicular germ cell tumours in Denmark 1976-1980. Pathology of 1058 consecutive cases. | journal=Acta Radiol Oncol | year= 1984 | volume= 23 | issue= 4 | pages= 239-47 | pmid=6093440 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6093440  }} </ref>
*
* [[Seminoma]]
==Genetics==
:*  
These are [[genes]] involved in the pathogenesis of testicular cancer:<ref name="pmid8527395">{{cite journal |vauthors=van Echten J, Oosterhuis JW, Looijenga LH, van de Pol M, Wiersema J, te Meerman GJ, Schaffordt Koops H, Sleijfer DT, de Jong B |title=No recurrent structural abnormalities apart from i(12p) in primary germ cell tumors of the adult testis |journal=Genes Chromosomes Cancer |volume=14 |issue=2 |pages=133–44 |date=October 1995 |pmid=8527395 |doi= |url=}}</ref><ref name="pmid9227931">{{cite journal |vauthors=Bosl GJ, Motzer RJ |title=Testicular germ-cell cancer |journal=N. Engl. J. Med. |volume=337 |issue=4 |pages=242–53 |date=July 1997 |pmid=9227931 |doi=10.1056/NEJM199707243370406 |url=}}</ref>
*[[Chromosome]] 12p
*12q22.2
 
==Immunohistochemical Markers==
*[[Germ]] [[cell]] [[neoplastic]] [[in situ]]:
**+PLAP (Placenta like-alkaline phosphatase)<ref name="pmid6209917">{{cite journal |vauthors=Jacobsen GK, Nørgaard-Pedersen B |title=Placental alkaline phosphatase in testicular germ cell tumours and in carcinoma-in-situ of the testis. An immunohistochemical study |journal=Acta Pathol Microbiol Immunol Scand A |volume=92 |issue=5 |pages=323–9 |date=September 1984 |pmid=6209917 |doi= |url=}}</ref>
*[[Seminoma]]<nowiki/>s:<ref name="pmid29262668">{{cite journal |vauthors=Boccellino M, Vanacore D, Zappavigna S, Cavaliere C, Rossetti S, D'Aniello C, Chieffi P, Amler E, Buonerba C, Di Lorenzo G, Di Franco R, Izzo A, Piscitelli R, Iovane G, Muto P, Botti G, Perdonà S, Caraglia M, Facchini G |title=Testicular cancer from diagnosis to epigenetic factors |journal=Oncotarget |volume=8 |issue=61 |pages=104654–104663 |date=November 2017 |pmid=29262668 |pmc=5732834 |doi=10.18632/oncotarget.20992 |url=}}</ref><ref name="pmid17527070">{{cite journal |vauthors=Santagata S, Ligon KL, Hornick JL |title=Embryonic stem cell transcription factor signatures in the diagnosis of primary and metastatic germ cell tumors |journal=Am. J. Surg. Pathol. |volume=31 |issue=6 |pages=836–45 |date=June 2007 |pmid=17527070 |doi=10.1097/PAS.0b013e31802e708a |url=}}</ref><ref name="pmid17117392">{{cite journal |vauthors=Cheng L, Sung MT, Cossu-Rocca P, Jones TD, MacLennan GT, De Jong J, Lopez-Beltran A, Montironi R, Looijenga LH |title=OCT4: biological functions and clinical applications as a marker of germ cell neoplasia |journal=J. Pathol. |volume=211 |issue=1 |pages=1–9 |date=January 2007 |pmid=17117392 |doi=10.1002/path.2105 |url=}}</ref>
**OCT3/4 [[transcription]] factors<ref name="pmid15818593">{{cite journal |vauthors=de Jong J, Stoop H, Dohle GR, Bangma CH, Kliffen M, van Esser JW, van den Bent M, Kros JM, Oosterhuis JW, Looijenga LH |title=Diagnostic value of OCT3/4 for pre-invasive and invasive testicular germ cell tumours |journal=J. Pathol. |volume=206 |issue=2 |pages=242–9 |date=June 2005 |pmid=15818593 |doi=10.1002/path.1766 |url=}}</ref>
**[[C-kit]]
**[[CD30]]
**D2-40 [[monoclonal antibody]]
**PLAP
**NANOG [[transcription factor]]
 
*[[Embryonal carcinoma]]:<ref name="pmid17527070">{{cite journal |vauthors=Santagata S, Ligon KL, Hornick JL |title=Embryonic stem cell transcription factor signatures in the diagnosis of primary and metastatic germ cell tumors |journal=Am. J. Surg. Pathol. |volume=31 |issue=6 |pages=836–45 |date=June 2007 |pmid=17527070 |doi=10.1097/PAS.0b013e31802e708a |url=}}</ref><ref name="pmid17117392">{{cite journal |vauthors=Cheng L, Sung MT, Cossu-Rocca P, Jones TD, MacLennan GT, De Jong J, Lopez-Beltran A, Montironi R, Looijenga LH |title=OCT4: biological functions and clinical applications as a marker of germ cell neoplasia |journal=J. Pathol. |volume=211 |issue=1 |pages=1–9 |date=January 2007 |pmid=17117392 |doi=10.1002/path.2105 |url=}}</ref>
**PLAP
**OCT3/4<ref name="pmid15818593">{{cite journal |vauthors=de Jong J, Stoop H, Dohle GR, Bangma CH, Kliffen M, van Esser JW, van den Bent M, Kros JM, Oosterhuis JW, Looijenga LH |title=Diagnostic value of OCT3/4 for pre-invasive and invasive testicular germ cell tumours |journal=J. Pathol. |volume=206 |issue=2 |pages=242–9 |date=June 2005 |pmid=15818593 |doi=10.1002/path.1766 |url=}}</ref>
**[[SOX2]]
**[[CD30]]
**+/-GpC3,[[keratin]]
 
*[[Yolk sac tumor]]:<ref name="pmid26612222">{{cite journal |vauthors=Howitt BE, Berney DM |title=Tumors of the Testis: Morphologic Features and Molecular Alterations |journal=Surg Pathol Clin |volume=8 |issue=4 |pages=687–716 |date=December 2015 |pmid=26612222 |doi=10.1016/j.path.2015.07.007 |url=}}</ref><ref name="pmid19365862">{{cite journal |vauthors=Cao D, Humphrey PA, Allan RW |title=SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors |journal=Cancer |volume=115 |issue=12 |pages=2640–51 |date=June 2009 |pmid=19365862 |doi=10.1002/cncr.24308 |url=}}</ref>
**+[[SALL4]]
**+AFP
**+[[GATA3]]
**+Glypican3
**+[[Keratin]]
**+/-[[C-kit]]


* Non-seminomas
*[[Choriocarcinoma]]:<ref name="pmid26612222">{{cite journal |vauthors=Howitt BE, Berney DM |title=Tumors of the Testis: Morphologic Features and Molecular Alterations |journal=Surg Pathol Clin |volume=8 |issue=4 |pages=687–716 |date=December 2015 |pmid=26612222 |doi=10.1016/j.path.2015.07.007 |url=}}</ref>
:* [[Embryonal carcinoma]]<ref name="pmid6155988">{{cite journal| author=Talerman A, Haije WG, Baggerman L| title=Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: correlation between endodermal sinus (yolk sac) tumor and raised serum AFP. | journal=Cancer | year= 1980 | volume= 46 | issue= 2 | pages= 380-5 | pmid=6155988 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6155988  }} </ref>
**+Ck7
::* Marked nuclear atypia
**+[[GATA3]]
**+[[HCG]]
**+/-[[SALL4]]


:* [[Yolk sac tumor]]<ref name="pmid6093440">{{cite journal| author=Krag Jacobsen G, Barlebo H, Olsen J, Schultz HP, Starklint H, Søgaard H et al.| title=Testicular germ cell tumours in Denmark 1976-1980. Pathology of 1058 consecutive cases. | journal=Acta Radiol Oncol | year= 1984 | volume= 23 | issue= 4 | pages= 239-47 | pmid=6093440 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6093440  }} </ref>
*Spermatocytic [[tumor]]:<ref name="pmid26612222">{{cite journal |vauthors=Howitt BE, Berney DM |title=Tumors of the Testis: Morphologic Features and Molecular Alterations |journal=Surg Pathol Clin |volume=8 |issue=4 |pages=687–716 |date=December 2015 |pmid=26612222 |doi=10.1016/j.path.2015.07.007 |url=}}</ref>
::* Blander cytomorphology
**+[[SALL4]]
::* Hyaline-type globules
**+/-[[C-kit]]
::* Schiller-Duval bodies


:* [[Choriocarcinoma]]  
*[[Teratoma]]:<ref name="pmid8583612">{{cite journal |vauthors=Simmonds PD, Lee AH, Theaker JM, Tung K, Smart CJ, Mead GM |title=Primary pure teratoma of the testis |journal=J. Urol. |volume=155 |issue=3 |pages=939–42 |date=March 1996 |pmid=8583612 |doi= |url=}}</ref><ref name="pmid377749">{{cite journal |vauthors=Brosman SA |title=Testicular tumors in prepubertal children |journal=Urology |volume=13 |issue=6 |pages=581–8 |date=June 1979 |pmid=377749 |doi= |url=}}</ref><ref name="pmid26612222">{{cite journal |vauthors=Howitt BE, Berney DM |title=Tumors of the Testis: Morphologic Features and Molecular Alterations |journal=Surg Pathol Clin |volume=8 |issue=4 |pages=687–716 |date=December 2015 |pmid=26612222 |doi=10.1016/j.path.2015.07.007 |url=}}</ref>
::* Both syncytiotrophoblasts and cytotrophoblast cells
**+[[SALL4]]
* Germ cell neoplasia in situ<ref name="pmid23478232">{{cite journal |vauthors=Emerson RE, Cheng L |title=Premalignancy of the testis and paratestis |journal=Pathology |volume=45 |issue=3 |pages=264–72 |date=April 2013 |pmid=23478232 |doi=10.1097/PAT.0b013e32835f3e1a |url=}}</ref><ref name="pmid29262668">{{cite journal |vauthors=Boccellino M, Vanacore D, Zappavigna S, Cavaliere C, Rossetti S, D'Aniello C, Chieffi P, Amler E, Buonerba C, Di Lorenzo G, Di Franco R, Izzo A, Piscitelli R, Iovane G, Muto P, Botti G, Perdonà S, Caraglia M, Facchini G |title=Testicular cancer from diagnosis to epigenetic factors |journal=Oncotarget |volume=8 |issue=61 |pages=104654–104663 |date=November 2017 |pmid=29262668 |pmc=5732834 |doi=10.18632/oncotarget.20992 |url=}}</ref>
**+[[Cytokeratin]]
::*Hyperchromatic nuclei
**+[[HCG]]
::*Prominent nucleoli
**+/-[[GATA3]],[[SOX2]],[[OCT4]]
::*Intact basement menbrane.


==Genetics==
*[[Testicular]] [[lymphoma]]:<ref name="pmid26612222">{{cite journal |vauthors=Howitt BE, Berney DM |title=Tumors of the Testis: Morphologic Features and Molecular Alterations |journal=Surg Pathol Clin |volume=8 |issue=4 |pages=687–716 |date=December 2015 |pmid=26612222 |doi=10.1016/j.path.2015.07.007 |url=}}</ref>
Genes involved in the pathogenesis of testicular cancer.
**+[[CD3]]
*4q22
**+[[CD20]]
*7q22
**+[[CD45]]
*16q22.3
 
*17q22
*[[Leydig cell tumor]]:<ref name="pmid17284120">{{cite journal |vauthors=Al-Agha OM, Axiotis CA |title=An in-depth look at Leydig cell tumor of the testis |journal=Arch. Pathol. Lab. Med. |volume=131 |issue=2 |pages=311–7 |date=February 2007 |pmid=17284120 |doi=10.1043/1543-2165(2007)131[311:AILALC]2.0.CO;2 |url=}}</ref><ref name="pmid9720507">{{cite journal |vauthors=Iczkowski KA, Bostwick DG, Roche PC, Cheville JC |title=Inhibin A is a sensitive and specific marker for testicular sex cord-stromal tumors |journal=Mod. Pathol. |volume=11 |issue=8 |pages=774–9 |date=August 1998 |pmid=9720507 |doi= |url=}}</ref>
**+[[Inhibin]]
**+[[Calretinin]]
**+Melan-A
**+[[Vimentin]]
 
*[[Sertoli cell]] [[tumor]]:<ref name="pmid15502809">{{cite journal |vauthors=Young RH |title=Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems |journal=Mod. Pathol. |volume=18 Suppl 2 |issue= |pages=S81–98 |date=February 2005 |pmid=15502809 |doi=10.1038/modpathol.3800311 |url=}}</ref><ref name="pmid9720507">{{cite journal |vauthors=Iczkowski KA, Bostwick DG, Roche PC, Cheville JC |title=Inhibin A is a sensitive and specific marker for testicular sex cord-stromal tumors |journal=Mod. Pathol. |volume=11 |issue=8 |pages=774–9 |date=August 1998 |pmid=9720507 |doi= |url=}}</ref><ref name="pmid17284120">{{cite journal |vauthors=Al-Agha OM, Axiotis CA |title=An in-depth look at Leydig cell tumor of the testis |journal=Arch. Pathol. Lab. Med. |volume=131 |issue=2 |pages=311–7 |date=February 2007 |pmid=17284120 |doi=10.1043/1543-2165(2007)131[311:AILALC]2.0.CO;2 |url=}}</ref>
**+[[Inhibin]]
**+[[Vimentin]]
**+EMA (epithelial menbrane antigen)
**+/-[[Cytokeratin]]
 
*[[Granulosa cell tumor]]:<ref name="pmid17628299">{{cite journal |vauthors=Ditonno P, Lucarelli G, Battaglia M, Mancini V, Palazzo S, Trabucco S, Bettocchi C, Paolo Selvaggi F |title=Testicular granulosa cell tumor of adult type: a new case and a review of the literature |journal=Urol. Oncol. |volume=25 |issue=4 |pages=322–5 |date=2007 |pmid=17628299 |doi=10.1016/j.urolonc.2006.08.019 |url=}}</ref><ref name="pmid15502809">{{cite journal |vauthors=Young RH |title=Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems |journal=Mod. Pathol. |volume=18 Suppl 2 |issue= |pages=S81–98 |date=February 2005 |pmid=15502809 |doi=10.1038/modpathol.3800311 |url=}}</ref><ref name="pmid9591732">{{cite journal |vauthors=McCluggage WG, Shanks JH, Whiteside C, Maxwell P, Banerjee SS, Biggart JD |title=Immunohistochemical study of testicular sex cord-stromal tumors, including staining with anti-inhibin antibody |journal=Am. J. Surg. Pathol. |volume=22 |issue=5 |pages=615–9 |date=May 1998 |pmid=9591732 |doi= |url=}}</ref>
**+[[Inhibin]]
**+[[Calretinin]]
**+[[Vimentin]]
**


==References==
==References==

Latest revision as of 09:25, 29 May 2019

Testicular cancer Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gertrude Djouka, M.D.[2], Shanshan Cen, M.D. [3]

Overview

The pathophysiology of testicular cancer depends on the histological cell subtypes and findings. Most testicular cancers derived from the lack of differentiation of primordial germ cell into spermatogonia. Germ cells testicular tumor have some genetic component while most sex cord stromal testicular cancer are hormonal dependent. Most gross pathology of testicular tumors look similar on the physical appearance. On microscopic histopathological analysis of testicular cancer, fried-egg appearance is the characteristic finding of seminoma; marked nuclear atypia is the characteristic finding of embryonal carcinoma; hyaline-type globules, and Schiller-Duval bodies are characteristic findings of yolk sac tumor  ; syncytiotrophoblasts and cytotrophoblast cells are the characteristic findings of choriocarcinoma, Polymorphism with"spirene" chromatin for spermatocytic.

Pathogenesis

Normal process of testicular germ cells

Normal process of testicular sex cord stromal

Leydig cells

Germ cells tumors

Germ cell tumors derived from germ cell neoplasia in situ

Germ cell tumors unrelated to germ cell neoplasia in situ

Testicular sex cord stromal tumors

Leydig cells tumor

Sertoli cell tumor

Granulosa cell tumor

Gross and Microscopic Pathology

The gross and microscopic features of the most common tumors are described below:[16][17][18][19][20][21][22][19][23][24][25][26][27][3][28][29][15]

Types Gross pathology Microscopic pathology Images
Germ cell neoplasia in situ
Contributed by Nephron in wikimedia.commons
Seminoma
  • Solid, firm without cross section
Contributed by Nephron in wikimedia.commons
Embryonal carcinoma
Contributed by Nephron in wikimedia.commons
Yolk sac tumor
Contributed by EDDAOUALLINE Hanane in wikimedia.commons
Choriocarcinoma
Contributed by Nephron in wikimedia.commons
Teratoma, postpubertal-type
Contributed by Nephron in wikimedia.commons
Mixed germ cell tumors
Contributed by Nephron in wikimedia.commons
Spermatocytic tumor
  • Soft, gray, and gelatinous mass
  • Well circumscribed with small hemorrhagic and necrotic foci.
Contributed by Nephron in wikimedia.commons
Teratoma, prepubertal-type,

Desmoid cyst

Epidermoid cyst

Contributed by Nephron in wikimedia.commons
Testicular lymphoma
  • Soft, gray, and gelatinous mass
  • Well circumscribed with small hemorrhagic and necrotic foci.
Contributed by Nephron in wikimedia.commons
Leydig cells tumor
Contributed by Nephron in wikimedia.commons
Sertoli tumor
  • White to grey on cut surface
Contributed by Nephron in wikimedia.commons
Granulosa tumor

Adult type

  • No distint feature

Juvenile type

Adult type

  • Cells are arranged in elongated, microfollicular "call-Exner bodies"

Juvenile type

Contributed by Nephron in wikimedia.commons

Genetics

These are genes involved in the pathogenesis of testicular cancer:[30][31]

Immunohistochemical Markers

References

  1. ↑ Miyai, Kosuke; Ito, Keiichi; Nakanishi, Kuniaki; Tsuda, Hitoshi (2019). "Seminoma component of mixed testicular germ cell tumor shows a higher incidence of loss of heterozygosity than pure-type seminoma". Human Pathology. 84: 71–80. doi:10.1016/j.humpath.2018.09.007. ISSN 0046-8177.
  2. ↑ 2.0 2.1 Kraggerud SM, Hoei-Hansen CE, Alagaratnam S, Skotheim RI, Abeler VM, Rajpert-De Meyts E, Lothe RA (June 2013). "Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: implications for pathogenesis". Endocr. Rev. 34 (3): 339–76. doi:10.1210/er.2012-1045. PMC 3787935. PMID 23575763.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 Al-Agha OM, Axiotis CA (February 2007). "An in-depth look at Leydig cell tumor of the testis". Arch. Pathol. Lab. Med. 131 (2): 311–7. doi:10.1043/1543-2165(2007)131[311:AILALC]2.0.CO;2. PMID 17284120.
  4. ↑ Neaves WB (May 1975). "Leydig cells". Contraception. 11 (5): 571–606. PMID 1095296.
  5. ↑ Bray F, Richiardi L, Ekbom A, Forman D, Pukkala E, Cuninkova M, Møller H (April 2006). "Do testicular seminoma and nonseminoma share the same etiology? Evidence from an age-period-cohort analysis of incidence trends in eight European countries". Cancer Epidemiol. Biomarkers Prev. 15 (4): 652–8. doi:10.1158/1055-9965.EPI-05-0565. PMID 16614105.
  6. ↑ Linke J, Loy V, Dieckmann KP (May 2005). "Prevalence of testicular intraepithelial neoplasia in healthy males". J. Urol. 173 (5): 1577–9. doi:10.1097/01.ju.0000154348.68575.95. PMID 15821489.
  7. ↑ Rosenberg C, Van Gurp RJ, Geelen E, Oosterhuis JW, Looijenga LH (November 2000). "Overrepresentation of the short arm of chromosome 12 is related to invasive growth of human testicular seminomas and nonseminomas". Oncogene. 19 (51): 5858–62. PMID 11127816.
  8. ↑ 8.0 8.1 Powles T, Bower M, Daugaard G, Shamash J, De Ruiter A, Johnson M, Fisher M, Anderson J, Mandalia S, Stebbing J, Nelson M, Gazzard B, Oliver T (May 2003). "Multicenter study of human immunodeficiency virus-related germ cell tumors". J. Clin. Oncol. 21 (10): 1922–7. doi:10.1200/JCO.2003.09.107. PMID 12743144.
  9. ↑ Rapley, Elizabeth A.; Crockford, Gillian P.; Teare, Dawn; Biggs, Patrick; Seal, Sheila; Barfoot, Rita; Edwards, Sandra; Hamoudi, Rifat; Heimdal, Ketil; Fosså, Sophie D.; Tucker, Kathy; Donald, Jenny; Collins, Felicity; Friedlander, Michael; Hogg, David; Goss, Paul; Heidenreich, Axel; Ormiston, Wilma; Daly, Peter A.; Forman, David; Oliver, Timothy D.; Leahy, Michael; Huddart, Robert; Cooper, Colin S.; Bodmer, Julia G.; Easton, Douglas F.; Stratton, Michael R.; Bishop, D. Timothy (2000). "Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours". Nature Genetics. 24 (2): 197–200. doi:10.1038/72877. ISSN 1061-4036.
  10. ↑ Hoei-Hansen CE, Rajpert-De Meyts E, Daugaard G, Skakkebaek NE (June 2005). "Carcinoma in situ testis, the progenitor of testicular germ cell tumours: a clinical review". Ann. Oncol. 16 (6): 863–8. doi:10.1093/annonc/mdi175. PMID 15821122.
  11. ↑ Looijenga LH (August 2011). "Spermatocytic seminoma: toward further understanding of pathogenesis". J. Pathol. 224 (4): 431–3. doi:10.1002/path.2939. PMID 21725972.
  12. ↑ 12.0 12.1 12.2 12.3 12.4 12.5 Howitt BE, Berney DM (December 2015). "Tumors of the Testis: Morphologic Features and Molecular Alterations". Surg Pathol Clin. 8 (4): 687–716. doi:10.1016/j.path.2015.07.007. PMID 26612222.
  13. ↑ Conkey DS, Howard GC, Grigor KM, McLaren DB, Kerr GR (August 2005). "Testicular sex cord-stromal tumours: the Edinburgh experience 1988-2002, and a review of the literature". Clin Oncol (R Coll Radiol). 17 (5): 322–7. PMID 16097561.
  14. ↑ Dilworth, J. Patrick; Farrow, George M.; Oesterling, Joseph E. (1991). "Non-germ cell tumors of testis". Urology. 37 (5): 399–417. doi:10.1016/0090-4295(91)80100-L. ISSN 0090-4295.
  15. ↑ 15.0 15.1 Jimenez-Quintero LP, Ro JY, Zavala-Pompa A, Amin MB, Tetu B, Ordoñez NG, Ayala AG (October 1993). "Granulosa cell tumor of the adult testis: a clinicopathologic study of seven cases and a review of the literature". Hum. Pathol. 24 (10): 1120–5. PMID 8406422.
  16. ↑ Boccellino M, Vanacore D, Zappavigna S, Cavaliere C, Rossetti S, D'Aniello C, Chieffi P, Amler E, Buonerba C, Di Lorenzo G, Di Franco R, Izzo A, Piscitelli R, Iovane G, Muto P, Botti G, Perdonà S, Caraglia M, Facchini G (November 2017). "Testicular cancer from diagnosis to epigenetic factors". Oncotarget. 8 (61): 104654–104663. doi:10.18632/oncotarget.20992. PMC 5732834. PMID 29262668.
  17. ↑ Howitt BE, Berney DM (December 2015). "Tumors of the Testis: Morphologic Features and Molecular Alterations". Surg Pathol Clin. 8 (4): 687–716. doi:10.1016/j.path.2015.07.007. PMID 26612222.
  18. ↑ Siegel RL, Miller KD, Jemal A (2016). "Cancer statistics, 2016". CA Cancer J Clin. 66 (1): 7–30. doi:10.3322/caac.21332. PMID 26742998.
  19. ↑ 19.0 19.1 Krag Jacobsen G, Barlebo H, Olsen J, Schultz HP, Starklint H, Søgaard H; et al. (1984). "Testicular germ cell tumours in Denmark 1976-1980. Pathology of 1058 consecutive cases". Acta Radiol Oncol. 23 (4): 239–47. PMID 6093440.
  20. ↑ Emerson RE, Cheng L (April 2013). "Premalignancy of the testis and paratestis". Pathology. 45 (3): 264–72. doi:10.1097/PAT.0b013e32835f3e1a. PMID 23478232.
  21. ↑ 21.0 21.1 Boccellino M, Vanacore D, Zappavigna S, Cavaliere C, Rossetti S, D'Aniello C, Chieffi P, Amler E, Buonerba C, Di Lorenzo G, Di Franco R, Izzo A, Piscitelli R, Iovane G, Muto P, Botti G, Perdonà S, Caraglia M, Facchini G (November 2017). "Testicular cancer from diagnosis to epigenetic factors". Oncotarget. 8 (61): 104654–104663. doi:10.18632/oncotarget.20992. PMC 5732834. PMID 29262668.
  22. ↑ Talerman A, Haije WG, Baggerman L (1980). "Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: correlation between endodermal sinus (yolk sac) tumor and raised serum AFP". Cancer. 46 (2): 380–5. PMID 6155988.
  23. ↑ 23.0 23.1 Simmonds PD, Lee AH, Theaker JM, Tung K, Smart CJ, Mead GM (March 1996). "Primary pure teratoma of the testis". J. Urol. 155 (3): 939–42. PMID 8583612.
  24. ↑ Shahab N, Doll DC (June 1999). "Testicular lymphoma". Semin. Oncol. 26 (3): 259–69. PMID 10375083.
  25. ↑ Chuang KL, Liaw CC, Ueng SH, Liao SK, Pang ST, Chang YH, Chuang HC, Chuang CK (March 2010). "Mixed germ cell tumor metastatic to the skin: case report and literature review". World J Surg Oncol. 8: 21. doi:10.1186/1477-7819-8-21. PMC 2851696. PMID 20331874.
  26. ↑ Ramón y Cajal S, Piñango L, Barat A, Moldenhauer F, Oliva H (March 1987). "Metastatic pure choriocarcinoma of the testis in an elderly man". J. Urol. 137 (3): 516–9. PMID 3820391.
  27. ↑ Wei Y, Wu S, Lin T, He D, Li X, Liu J, Liu X, Hua Y, Lu P, Wei G (December 2014). "Testicular yolk sac tumors in children: a review of 61 patients over 19 years". World J Surg Oncol. 12: 400. doi:10.1186/1477-7819-12-400. PMC 4326497. PMID 25547829.
  28. ↑ Cheville JC, Sebo TJ, Lager DJ, Bostwick DG, Farrow GM (November 1998). "Leydig cell tumor of the testis: a clinicopathologic, DNA content, and MIB-1 comparison of nonmetastasizing and metastasizing tumors". Am. J. Surg. Pathol. 22 (11): 1361–7. PMID 9808128.
  29. ↑ 29.0 29.1 29.2 Young RH (February 2005). "Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems". Mod. Pathol. 18 Suppl 2: S81–98. doi:10.1038/modpathol.3800311. PMID 15502809.
  30. ↑ van Echten J, Oosterhuis JW, Looijenga LH, van de Pol M, Wiersema J, te Meerman GJ, Schaffordt Koops H, Sleijfer DT, de Jong B (October 1995). "No recurrent structural abnormalities apart from i(12p) in primary germ cell tumors of the adult testis". Genes Chromosomes Cancer. 14 (2): 133–44. PMID 8527395.
  31. ↑ Bosl GJ, Motzer RJ (July 1997). "Testicular germ-cell cancer". N. Engl. J. Med. 337 (4): 242–53. doi:10.1056/NEJM199707243370406. PMID 9227931.
  32. ↑ Jacobsen GK, Nørgaard-Pedersen B (September 1984). "Placental alkaline phosphatase in testicular germ cell tumours and in carcinoma-in-situ of the testis. An immunohistochemical study". Acta Pathol Microbiol Immunol Scand A. 92 (5): 323–9. PMID 6209917.
  33. ↑ 33.0 33.1 Santagata S, Ligon KL, Hornick JL (June 2007). "Embryonic stem cell transcription factor signatures in the diagnosis of primary and metastatic germ cell tumors". Am. J. Surg. Pathol. 31 (6): 836–45. doi:10.1097/PAS.0b013e31802e708a. PMID 17527070.
  34. ↑ 34.0 34.1 Cheng L, Sung MT, Cossu-Rocca P, Jones TD, MacLennan GT, De Jong J, Lopez-Beltran A, Montironi R, Looijenga LH (January 2007). "OCT4: biological functions and clinical applications as a marker of germ cell neoplasia". J. Pathol. 211 (1): 1–9. doi:10.1002/path.2105. PMID 17117392.
  35. ↑ 35.0 35.1 de Jong J, Stoop H, Dohle GR, Bangma CH, Kliffen M, van Esser JW, van den Bent M, Kros JM, Oosterhuis JW, Looijenga LH (June 2005). "Diagnostic value of OCT3/4 for pre-invasive and invasive testicular germ cell tumours". J. Pathol. 206 (2): 242–9. doi:10.1002/path.1766. PMID 15818593.
  36. ↑ Cao D, Humphrey PA, Allan RW (June 2009). "SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors". Cancer. 115 (12): 2640–51. doi:10.1002/cncr.24308. PMID 19365862.
  37. ↑ Brosman SA (June 1979). "Testicular tumors in prepubertal children". Urology. 13 (6): 581–8. PMID 377749.
  38. ↑ 38.0 38.1 Iczkowski KA, Bostwick DG, Roche PC, Cheville JC (August 1998). "Inhibin A is a sensitive and specific marker for testicular sex cord-stromal tumors". Mod. Pathol. 11 (8): 774–9. PMID 9720507.
  39. ↑ Ditonno P, Lucarelli G, Battaglia M, Mancini V, Palazzo S, Trabucco S, Bettocchi C, Paolo Selvaggi F (2007). "Testicular granulosa cell tumor of adult type: a new case and a review of the literature". Urol. Oncol. 25 (4): 322–5. doi:10.1016/j.urolonc.2006.08.019. PMID 17628299.
  40. ↑ McCluggage WG, Shanks JH, Whiteside C, Maxwell P, Banerjee SS, Biggart JD (May 1998). "Immunohistochemical study of testicular sex cord-stromal tumors, including staining with anti-inhibin antibody". Am. J. Surg. Pathol. 22 (5): 615–9. PMID 9591732.


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