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]]; | |||
==Pathogenesis== | ==Pathogenesis== | ||
==Normal process of testicular germ cells== | ===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]] | ||
==Normal process of testicular sex cord stromal== | ===Normal process of testicular sex cord stromal=== | ||
====Leydig cells==== | ====Leydig cells==== | ||
*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> | *[[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> | ||
*Leydig cells secrete testosterone hormone under the signal of luteinizing hormone | *[[Leydig cells]] secrete [[testosterone]] [[hormone]] under the signal of [[luteinizing hormone]]. | ||
*Leydig cells are involved in the | *[[Leydig cells]] are involved in the [[Development|developmen]]<nowiki/>t of [[male]] [[secondary sexual characteristics]] and [[spermatogenesis]]. | ||
=Germ cells tumors= | ==Germ cells tumors== | ||
==Germ cell tumors derived from germ cell neoplasia in situ== | ===Germ cell tumors derived from germ cell neoplasia in situ=== | ||
* Lack of | * 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> | ||
* Germ cell neoplasia in Situ may gain some abnormal chromosome(12), then it leads to seminomas and nonseminomas cancers. | * [[Germ cell]] [[neoplasia]] in Situ may gain some abnormal [[chromosome]](12), then it leads to [[Seminoma|seminomas]] and [[Nonseminoma|nonseminomas cancers]]. | ||
*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> | *[[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> | ||
* | **[[Aneuploid]] | ||
*Loss of chromosomes 4,5,11,13,18, and Y | **Loss of [[chromosomes]] 4,5,11,13,18, and Y | ||
*Gain of chromosomes 7,8,12, and X | **Gain of [[chromosomes]] 7,8,12, and X | ||
* 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. | * 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. | ||
* About 50% of all germ cell tumors are seminomas, or seminomatous germ cell tumours. They grow slower than non-seminomas. | * About 50% of all [[germ cell tumors]] are [[Seminoma|seminomas]], or [[seminomatous germ cell tumours]]. They grow slower than [[Nonseminoma|non-seminomas]]. | ||
* 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> | * 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> | ||
* 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> | * 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> | ||
* 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> | * [[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> | ||
* | * [[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> | ||
**Gene on chromosome Xq27 may be related to testicular germ cell tumors | **[[Gene]] on [[chromosome]] Xq27 may be related to testicular [[germ cell tumors]] | ||
* 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> | * 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== | ===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> | *[[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 | *Mostly located in the [[testis]] and rarely [[metastases]]. | ||
*Mutated proteins | *[[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> | *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= | |||
==Testicular sex cord stromal tumors== | |||
===Leydig cells tumor=== | ===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> | *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. | *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 | *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><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> | 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 54: | Line 59: | ||
!Images | !Images | ||
|- | |- | ||
![[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 | * [[Hyperchromatic]] [[nuclei]] | ||
*Prominent nucleoli and clear cytoplasm | *Prominent [[nucleoli]] and clear [[cytoplasm]] | ||
*Thickened basement menbrane | *[[Thickened]] basement menbrane | ||
*Proliferation of tumor germ cell in the seminiferous tubules | *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]] | | [[File:Intratubular germ cell neoplasia - 2 - very high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | ||
|- | |- | ||
![[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 cytoplasm due to the presence of glycogen | * Large [[nucleoli]] with clear to pale to [[eosinophilic]] [[cytoplasm]] due to the presence of [[glycogen]] | ||
* Clonal proliferation of neoplastic [[germ cells]] | * [[Clonal]] proliferation of [[neoplastic]] [[germ cells]] | ||
* Fried-egg appearance | * [[Fried-egg]] appearance | ||
* Prominent mitotic figures | * Prominent [[mitotic]] figures | ||
* Nests and sheets of cancer cells with "squared-off" nuclei | * [[Nests]] and sheets of cancer cells with "squared-off" nuclei | ||
* Granulomatous inflammation | * [[Granulomatous]] [[inflammation]] | ||
| [[File:Intertubular seminoma -- intermed mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | | [[File:Intertubular seminoma -- intermed mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | ||
|- | |- | ||
![[Embryonal carcinoma]] | |||
| | | | ||
* Poorly demarcated mass | * Poorly demarcated [[mass]] | ||
* Soft gray on cut surface | * [[Soft|Soft gray]] on cut surface | ||
* Large hemorraghic and necrotic foci. | * Large hemorraghic and [[necrotic]] foci. | ||
| | | | ||
* Presents with mixed histological features (solid, papular, glandular) | * Presents with mixed [[histological]] features ([[solid]], papular, glandular) | ||
* Marked nuclear atypia | * Marked [[Nuclear|nuclear atypia]] | ||
* Marked epithelial cells with polymorphism | * Marked [[epithelial cells]] with [[polymorphism]] | ||
* Large nuclei with abundant amphophilic cytoplasm | * Large [[nuclei]] with abundant [[amphophilic]] [[cytoplasm]] | ||
* Prominent mitotic activities | * Prominent [[mitotic]] activities | ||
|[[File:Embryonal carcinoma - high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | |[[File:Embryonal carcinoma - high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | ||
|- | |- | ||
![[Yolk sac tumor]] | |||
| | | | ||
*Solid, lobulated, soft, mucinous on cut surface | *[[Solid]], lobulated, soft, [[mucinous]] on cut surface | ||
*Gray and grayish yellow mass | *Gray and grayish [[yellow]] [[mass]] | ||
*May have small hemorrhagic and necrotic foci | *May have small hemorrhagic and [[necrotic]] foci | ||
*Heterogenous mass | *[[Heterogenous]] [[mass]] | ||
| | | | ||
*Hyaline-type globules | *Hyaline-type [[globules]] | ||
* Schiller-Duval bodies | * Schiller-Duval bodies | ||
* Multiple histological patterns such as recticular, microcystic, glandular, papillary, hepatoid, and solid | * Multiple [[histological]] patterns such as [[recticular]], [[microcystic]], [[glandular]], [[papillary]], hepatoid, and [[solid]] | ||
* Associated with myxoid stroma | * Associated with [[myxoid]] [[stroma]] | ||
* Variable cytologic atypia | * Variable [[cytologic]] [[atypia]] | ||
|[[File:Shiller Duval body.jpg|thumb|none|300px|Contributed by EDDAOUALLINE Hanane in wikimedia.commons]] | |[[File:Shiller Duval body.jpg|thumb|none|300px|Contributed by EDDAOUALLINE Hanane in wikimedia.commons]] | ||
|- | |- | ||
![[Choriocarcinoma]] | |||
| | | | ||
* Hemorrhagic and necrotic nodules | * Hemorrhagic and [[necrotic]] [[nodules]] | ||
* May appear more cystic and calcified in homogeneous | * May appear more [[cystic]] and calcified in [[homogeneous]] | ||
| | | | ||
* More Hemorrhagic and necrotic | * More Hemorrhagic and [[necrotic]] | ||
* Made up of mononucleated trophoblast and multinucleated syncytiotrophoblast cells | * Made up of [[mononucleated]] [[trophoblast]] and [[multinucleated]] syncytiotrophoblast [[cells]] | ||
* Hyperchomatic cytoplasm | * Hyperchomatic [[cytoplasm]] | ||
|[[File:Choriocarcinoma - high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | |[[File:Choriocarcinoma - high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | ||
|- | |- | ||
![[Teratoma]], postpubertal-type | |||
| | | | ||
* Hetereogenous, cystic and irregular calcification on appearance | * Hetereogenous, [[cystic]] and irregular [[calcification]] on appearance | ||
* Solid, firm mass | * [[Solid]], firm [[mass]] | ||
| | | | ||
* Arrange in disorder fashion | * Arrange in disorder fashion | ||
* Cytologic atypia | * [[Cytological|Cytologic]] [[atypia]] | ||
* High mitotic activities | * High [[mitotic]] activities | ||
* Presence of 3 germ cells layers | * Presence of 3 [[germ]] [[cells]] layers | ||
* Presence of immature elements with primitive nuclei | * Presence of [[immature]] elements with [[primitive]] [[nuclei]] | ||
|[[File:Immature teratoma high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | |[[File:Immature teratoma high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | ||
|- | |- | ||
!Mixed [[germ cell tumors]] | |||
| | | | ||
* Solid and cystic mass | * [[Solid]] and [[cystic]] [[mass]] | ||
* More hemorhragic and necrotic. | * More hemorhragic and [[necrotic]]. | ||
| | | | ||
*Microscopic findings are variable depending on the tumor type | *[[Microscopic]] findings are variable depending on the [[tumor]] type | ||
*May have the component of | *May have the component of [[yolk sac]] and [[choriocarcinoma]] | ||
|[[File:Mixed germ cell tumour - high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | |[[File:Mixed germ cell tumour - high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | ||
|- | |- | ||
!Spermatocytic [[tumor]] | |||
| | | | ||
* Soft, gray, and gelatinous mass | * Soft, gray, and gelatinous [[mass]] | ||
* Well circumscribed with small hemorrhagic and necrotic foci. | * Well circumscribed with small hemorrhagic and [[necrotic]] foci. | ||
| | | | ||
* Atyical mitoses | * Atyical [[mitoses]] activities | ||
* Eosinophilic cytoplasm without glycogen | * [[Eosinophilic]] [[cytoplasm]] without glycogen | ||
* Tumors cells with three different sizes (small, intermediate, and large) | * [[Tumors]] cells with three different sizes (small, intermediate, and large) | ||
* Polymorphism with"spirene" chromatin find in the giant cells | * [[Polymorphism]] with"spirene" [[chromatin]] find in the [[giant cells]] | ||
*<nowiki/>Freque<nowiki/>nt apoptosis | *<nowiki/>Freque<nowiki/>nt [[apoptosis]] | ||
|[[File:Spermatocytic seminoma high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | |[[File:Spermatocytic seminoma high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | ||
|- | |- | ||
![[Teratoma]], prepubertal-type, | |||
Desmoid cyst | [[Desmoid Tumor|Desmoid]] [[cyst]] | ||
Epidermoid cyst | [[Epidermoid cyst|Epidermoid]] [[cyst]] | ||
| | | | ||
* Solid and firm mass | * [[Solid]] and firm [[mass]] | ||
| | | | ||
* Lack of cytologic atypia | * Lack of cytologic [[atypia]] | ||
* No mitotic activities | * No [[mitotic]] activities | ||
* Absence of immature elements | * Absence of immature elements | ||
* Desmoid cyst has polosebaceous cells | * [[Desmoid tumor|Desmoid]] cyst has polosebaceous cells | ||
* Epidermoist cyst is surrounded with squamous epithelial 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]] | |[[File:Epidermoid cyst of testis -- high mag.jpg|thumb|none|100px|Contributed by Nephron in wikimedia.commons]] | ||
|- | |- | ||
![[Testicular]] [[lymphoma]] | |||
| | | | ||
* Soft, gray, and gelatinous mass | * Soft, gray, and gelatinous [[mass]] | ||
* Well circumscribed with small hemorrhagic and necrotic foci. | * Well circumscribed with small hemorrhagic and [[necrotic]] foci. | ||
| | | | ||
* Vascular invasion | * Vascular invasion | ||
* Pleomorphic tumor cells | * [[Pleomorphic]] tumor cells | ||
* Large irregular nuclei | * Large irregular [[nuclei]] | ||
|[[File:DLBCL of testis -- very high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | |[[File:DLBCL of testis -- very high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | ||
|- | |- | ||
|- | |- | ||
|Leydig cells tumor | ![[Leydig cells|Leydig cells tumor]] | ||
| | | | ||
* Homogeneous and well circumscribed mass | * [[Homogeneous]] and well circumscribed [[mass]] | ||
* Solitary and unilateral mass | * [[Solitary]] and unilateral [[mass]] | ||
* White to brown to yellow on cut surface | * White to [[brown]] to yellow on cut surface | ||
| | | | ||
* Cells are arranged in nest, sheets polygonal fahsion | * [[Cells]] are arranged in nest, sheets polygonal fahsion | ||
* Cytoplasm is eosinophilic with round nuclei and prominent nucleoli | * [[Cytoplasm]] is [[eosinophilic]] with round [[nuclei]] and prominent [[nucleoli]] | ||
* Presence of lipofuscin pigment and reinke crystal intracytoplasmic | * 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]] | ||
|- | |- | ||
|Sertoli tumor | ![[Sertoli cell|Sertoli tumor]] | ||
| | | | ||
* Homogeneous and well circumscribed mass | * [[Homogeneous]] and well circumscribed [[mass]] | ||
* White to grey on cut surface | * White to grey on cut surface | ||
* | * | ||
| | | | ||
* Cells are arranged in cords, nests and lobulated tubules | * [[Cells]] are arranged in [[Cord|cords]], nests and lobulated [[tubules]] | ||
* Fibrous stroma ans septa with lymphocytes | * [[Fibrous]] [[stroma]] ans septa with [[lymphocytes]] | ||
* Elongated spaces and microscysts | * Elongated spaces and microscysts | ||
* Pale lipid- rich cytoplasm | * Pale lipid- rich [[cytoplasm]] | ||
* No prominent nucleoli | * No prominent [[nucleoli]] | ||
|[[File:Sertoli cell tumour high mag.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | |||
|- | |||
| | |||
![[Granulosa|Granulosa tumor]] | |||
|Granulosa tumor | |||
| | | | ||
Adult type | Adult type | ||
Line 220: | Line 223: | ||
* No distint feature | * No distint feature | ||
Juvenile type | Juvenile type | ||
* Solid, nodule yellow-orange and cystic mass | * [[Solid]], [[nodule]] yellow-orange and [[cystic]] [[mass]] | ||
* | * | ||
| | | | ||
Adult type | Adult type | ||
* Cells are arranged in elongated, microfollicular "call-Exner bodies" | * [[Cells]] are arranged in elongated, microfollicular "call-Exner bodies" | ||
Juvenile type | Juvenile type | ||
*Cells are presented in solid sheets and nodules and form the estatic space | *[[Cells]] are presented in [[solid]] sheets and [[nodules]] and form the estatic space | ||
*Eosinophilic | *[[Eosinophilic]] [[cytoplasm]] | ||
*Hyperchromatic, round to oval nuclei | *Hyperchromatic, round to oval [[nuclei]] | ||
*High mitotic activities | *High [[mitotic]] activities | ||
*Follicles are located on the periphery | *[[Follicle|Follicles]] are located on the periphery | ||
| | |[[File:Granulosa cell tumour2.jpg|thumb|none|300px|Contributed by Nephron in wikimedia.commons]] | ||
|- | |- | ||
|} | |} | ||
* | * | ||
==Genetics== | ==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> | 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 | *12q22.2 | ||
==Immunohistochemical Markers== | ==Immunohistochemical Markers== | ||
Germ cell | *[[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> | **+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]] | |||
*[[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> | |||
**+Ck7 | |||
**+[[GATA3]] | |||
**+[[HCG]] | |||
**+/-[[SALL4]] | |||
*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> | |||
**+[[SALL4]] | |||
**+/-[[C-kit]] | |||
*[[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> | |||
**+[[SALL4]] | |||
**+[[Cytokeratin]] | |||
**+[[HCG]] | |||
**+/-[[GATA3]],[[SOX2]],[[OCT4]] | |||
*[[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> | |||
**+[[CD3]] | |||
**+[[CD20]] | |||
**+[[CD45]] | |||
*[[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 |
Diagnosis |
---|
Treatment |
Case Studies |
Testicular cancer pathophysiology On the Web |
American Roentgen Ray Society Images of Testicular cancer pathophysiology |
Risk calculators and risk factors for Testicular cancer pathophysiology |
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
- Primordial germ cell mass leads to gonocytes through cell proliferation
- Gonocytes differentiate into spermatogonia
Normal process of testicular sex cord stromal
Leydig cells
- Leydig cells are found in the seminiferous tubules of the testis.[3][4]
- Leydig cells secrete testosterone hormone under the signal of luteinizing hormone.
- Leydig cells are involved in the development of male secondary sexual characteristics and spermatogenesis.
Germ cells tumors
Germ cell tumors derived from germ cell neoplasia in situ
- Lack of primordial germ cell to differentiate into spermatogonia leads to germ cell neoplasia in Situ[2]
- Germ cell neoplasia in Situ may gain some abnormal chromosome(12), then it leads to seminomas and nonseminomas cancers.
- Seminomas and non seminotous germ cell tumors have similar pathogenesis.[5][6]
- Aneuploid
- Loss of chromosomes 4,5,11,13,18, and Y
- Gain of chromosomes 7,8,12, and X
- 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 sperms.
- About 50% of all germ cell tumors are seminomas, or seminomatous germ cell tumours. They grow slower than non-seminomas.
- Overrepresentation of short arm of chromosomes 12p may be related to invasive growth of seminomas and nonseminomatous testicular cancer.[7]
- Seminomas tumors may have both genetic and immune components due to lymphocytes infiltration in HIV patients.[8]
- Histological of seminomas tumor in HIV patients: tumor infiltrated by lymphocytes which may lead to weak immune system response.[8]
- Familial contribution:[9]
- Gene on chromosome Xq27 may be related to testicular germ cell tumors
- Some proteins such as C-kit (receptor) and placental-like alkaline phosphatase (PLAP) may be excessively expressed[10]
- Mutations from the proteins that may be involved in the maturation of the spermatogonia.[11]
- 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.[12]
Testicular sex cord stromal tumors
Leydig cells tumor
- The pathogenesis of leydig cells tumors is not well understood.[3][13]
- 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.[14]
Granulosa cell tumor
- It involved in hyperestrogenism due to an unregulated aromatase enzyme activity that leads to excessive production of hormones.[15]
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 |
|
|
|
Seminoma |
|
|
|
Embryonal carcinoma |
|
||
Yolk sac tumor |
|
|
|
Choriocarcinoma |
|
|
|
Teratoma, postpubertal-type |
|
||
Mixed germ cell tumors |
|
||
Spermatocytic tumor |
|
||
Teratoma, prepubertal-type, |
|
||
Testicular lymphoma |
|
||
Leydig cells tumor |
|
|
|
Sertoli tumor |
|
||
Granulosa tumor |
Adult type
Juvenile type |
Adult type
Juvenile type |
Genetics
These are genes involved in the pathogenesis of testicular cancer:[30][31]
- Chromosome 12p
- 12q22.2
Immunohistochemical Markers
- Germ cell neoplastic in situ:
- +PLAP (Placenta like-alkaline phosphatase)[32]
- Seminomas:[21][33][34]
- OCT3/4 transcription factors[35]
- C-kit
- CD30
- D2-40 monoclonal antibody
- PLAP
- NANOG transcription factor
- Leydig cell tumor:[3][38]
- +Inhibin
- +Calretinin
- +Melan-A
- +Vimentin
- Sertoli cell tumor:[29][38][3]
- +Inhibin
- +Vimentin
- +EMA (epithelial menbrane antigen)
- +/-Cytokeratin
References
- ↑ 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.
- ↑ 2.0 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.
- ↑ 3.0 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.
- ↑ Neaves WB (May 1975). "Leydig cells". Contraception. 11 (5): 571–606. PMID 1095296.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 8.0 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.
- ↑ 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.
- ↑ 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.
- ↑ Looijenga LH (August 2011). "Spermatocytic seminoma: toward further understanding of pathogenesis". J. Pathol. 224 (4): 431–3. doi:10.1002/path.2939. PMID 21725972.
- ↑ 12.0 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.
- ↑ 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.
- ↑ 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.
- ↑ 15.0 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 19.0 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.
- ↑ Emerson RE, Cheng L (April 2013). "Premalignancy of the testis and paratestis". Pathology. 45 (3): 264–72. doi:10.1097/PAT.0b013e32835f3e1a. PMID 23478232.
- ↑ 21.0 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.
- ↑ 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.
- ↑ 23.0 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.
- ↑ Shahab N, Doll DC (June 1999). "Testicular lymphoma". Semin. Oncol. 26 (3): 259–69. PMID 10375083.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 29.0 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.
- ↑ 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.
- ↑ Bosl GJ, Motzer RJ (July 1997). "Testicular germ-cell cancer". N. Engl. J. Med. 337 (4): 242–53. doi:10.1056/NEJM199707243370406. PMID 9227931.
- ↑ 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.
- ↑ 33.0 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.
- ↑ 34.0 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.
- ↑ 35.0 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.
- ↑ 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.
- ↑ Brosman SA (June 1979). "Testicular tumors in prepubertal children". Urology. 13 (6): 581–8. PMID 377749.
- ↑ 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.
- ↑ 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.
- ↑ 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.