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Smith&Tanagho'sGeneralUrology,18e>

Chapter24.GenitalTumors
JosephC.Presti,MD

TumorsoftheTestis
GermCellTumorsoftheTestis
EpidemiologyandRiskFactors
Malignanttumorsofthetestisarerare,withapproximately9newcasesper100,000malesreportedinthe
UnitedStateseachyear.Ofallprimarytesticulartumors,9095%aregermcelltumors(seminomaand
nonseminoma),whiletheremaindersarenongerminalneoplasms(Leydigcell,Sertolicell,gonadoblastoma).
Thelifetimeprobabilityofdevelopingtesticularcanceris0.2%forawhitemaleintheUnitedStates.Survival
ofpatientswithtesticularcancerhasimproveddramaticallyinrecentyears,reflectingthedevelopmentand
refinementofeffectivecombinationchemotherapy.Ofthe8480newcasesoftesticularcancerintheUnited
Statesin2010,only350deathsareexpected.
Theincidenceoftesticularcancershowsmarkedvariationamongdifferentcountries,races,and
socioeconomicclasses.Scandinaviancountriesreportupto6.7newcasesper100,000malesannuallyJapan
reports0.8per100,000males.IntheUnitedStates,theincidenceoftesticularcancerinblacksis
approximatelyonefourththatinwhites.Withinagivenrace,individualsinthehighersocioeconomicclasses
haveapproximatelytwicetheincidenceofthoseinthelowerclasses.
Testicularcancerisslightlymorecommonontherightsidethanontheleft,whichparallelstheincreased
incidenceofcryptorchidismontherightside.Ofprimarytesticulartumors,12%arebilateral,andabout50%
ofthesetumorsoccurinmenwithahistoryofunilateralorbilateralcryptorchidism.Primarybilateraltumors
ofthetestismayhappensynchronouslyorasynchronouslybuttendtobeofthesamehistologictype.
Seminomaisthemostcommongermcelltumorinbilateralprimarytesticulartumors,whilemalignant
lymphomaisthemostcommonbilateraltumorofthetestis.
Althoughthecauseoftesticularcancerisunknown,bothcongenitalandacquiredfactorshavebeenassociated
withtumordevelopment.Thestrongestassociationhasbeenwiththecryptorchidtestis.Approximately710%
oftesticulartumorsdevelopinpatientswhohaveahistoryofcryptorchidismseminomaisthemostcommon
formoftumorthesepatientshave.However,510%oftesticulartumorsoccurinthecontralateral,normally
descendedtestis.Therelativeriskofmalignancyishighestfortheintraabdominaltestis(1in20)andis
significantlylowerfortheinguinaltestis(1in80).Placementofthecryptorchidtestisintothescrotum
(orchiopexy)lowerstheriskofmalignancyifitisperformedpriortotheageof13(Petterssonetal,2007).
Exogenousestrogenadministrationtothemotherduringpregnancyhasbeenassociatedwithanincreased
relativeriskfortesticulartumorsinthefetus,rangingfrom2.8to5.3overtheexpectedincidence.Other
acquiredfactorssuchastraumaandinfectionrelatedtesticularatrophyhavebeenassociatedwithtesticular
tumorshowever,acausalrelationshiphasnotbeenestablished.

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Classification
Numerousclassificationsystemshavebeenproposedforgermcelltumorsofthetestis.Classificationby
histologictypeprovestobethemostusefulwithrespecttotreatment.Thetwomajordivisionsareseminoma
andnonseminomatousgermcelltumors(NSGCTs),whichincludeembryonal,teratoma,choriocarcinoma,and
mixedtumors.
TumorigenicHypothesisforGermCellTumorDevelopment
Duringembryonaldevelopment,thetotipotentialgermcellscantraveldownnormaldifferentiationpathways
andbecomespermatocytes.However,ifthesetotipotentialgermcellstraveldownabnormaldevelopmental
pathways,seminomaorembryonalcarcinomas(totipotentialtumorcells)develop.Iftheembryonalcells
undergofurtherdifferentiationalongintraembryonicpathways,teratomawillresult.Iftheembryonalcells
undergofurtherdifferentiationalongextraembryonicpathways,eitherchoriocarcinomaoryolksactumorsare
formed(Figure241).Thismodelhelpstoexplainwhyspecifichistologicpatternsoftesticulartumors
producecertaintumormarkers.Notethatyolksactumorsproducealphafetoprotein(AFP)justastheyolksac
producesAFPinnormaldevelopment.Likewise,choriocarcinomaproduceshumanchorionicgonadotropin
(hCG)justasthenormalplacentaproduceshCG.
Figure241.

Tumorigenicmodelforgermcelltumorsofthetestis.
Pathology
Seminoma(35%)

Threehistologicsubtypesofpureseminomahavebeendescribed.However,stageforstage,thereisno
prognosticsignificancetoanyofthesesubtypes.Classicseminomaaccountsfor85%ofallseminomasandis
mostcommoninthefourthdecadeoflife.Grossly,coalescinggraynodulesareobserved.Microscopically,
monotonoussheetsoflargecellswithclearcytoplasmanddenselystainingnucleiareseen.Itisnoteworthy
thatsyncytiotrophoblasticelementsareseeninapproximately1015%ofcases,anincidencethatcorresponds
approximatelytotheincidenceofhCGproductioninseminomas.
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Anaplasticseminomaaccountsfor510%ofallseminomas.Diagnosisrequiresthepresenceofthreeormore
mitosesperhighpowerfield,andthecellsdemonstrateahigherdegreeofnuclearpleomorphismthanthe
classictypes.Anaplasticseminomatendstopresentatahigherstagethantheclassicvariety.Whenstageis
takenintoconsideration,however,thissubtypedoesnotconveyaworseprognosis.
Spermatocyticseminomaaccountsfor510%ofallseminomas.Microscopically,cellsvaryinsizeandare
characterizedbydenselystainingcytoplasmandroundnucleithatcontaincondensedchromatin.Morethan
halfofthepatientswithspermatocyticseminomaareolderthan50years.
EmbryonalCellCarcinoma(20%)

Twovariantsofembryonalcellcarcinomaarecommon:theadulttypeandtheinfantiletypeoryolksactumor
(alsocalledendodermalsinustumor).Histologicstructureoftheadultvariantdemonstratesmarked
pleomorphismandindistinctcellularborders.Mitoticfiguresandgiantcellsarecommon.Cellsmaybe
arrangedinsheets,cords,glands,orpapillarystructures.Extensivehemorrhageandnecrosismaybeobserved
grossly.
Theinfantilevariant,oryolksactumor,isthemostcommontesticulartumorofinfantsandchildren.When
seeninadults,itusuallyoccursinmixedhistologictypesandpossiblyisresponsibleforAFPproductionin
thesetumors.Microscopically,cellsdemonstratevacuolatedcytoplasmsecondarytofatandglycogen
depositionandarearrangedinaloosenetworkwithlargeinterveningcysticspaces.Embryoidbodiesare
commonlyseenandresemble1to2weekoldembryosconsistingofacavitysurroundedbysyncytioand
cytotrophoblasts.
Teratoma(5%)

Teratomasmaybeseeninbothchildrenandadults.Theycontainmorethanonegermcelllayerinvarious
stagesofmaturationanddifferentiation.Grossly,thetumorappearslobulatedandcontainsvariablesizedcysts
filledwithgelatinousormucinousmaterial.Matureteratomamayhaveelementsresemblingbenignstructures
derivedfromectoderm,mesoderm,andendoderm,whileimmatureteratomaconsistsofundifferentiated
primitivetissue.Incontrasttoitsovariancounterpart,thematureteratomaofthetestisdoesnotattainthesame
degreeofdifferentiationasteratomaoftheovary.Microscopically,ectodermmayberepresentedbysquamous
epitheliumorneuraltissueendodermmayberepresentedbyintestinal,pancreatic,orrespiratorytissueand
mesodermmayberepresentedbysmoothorskeletalmuscle,cartilage,orbone.
Choriocarcinoma(<1%)

Purechoriocarcinomaisrare.Lesionstendtobesmallwithinthetestisandusuallydemonstratecentral
hemorrhageongrossinspection.Microscopically,syncytioandcytotrophoblastsmustbevisualized.The
syncytialelementsaretypicallylarge,multinucleatedcellswithvacuolated,eosinophiliccytoplasmthenuclei
arelarge,hyperchromatic,andirregular.Cytotrophoblastsareuniformcellswithdistinctcellborders,clear
cytoplasm,andasinglenucleus.
Clinically,choriocarcinomasbehaveinanaggressivefashioncharacterizedbyearlyhematogenousspread.
Paradoxically,smallintratesticularlesionscanbeassociatedwithwidespreadmetastaticdisease.
MixedCellType(40%)

Withinthecategoryofmixedcelltypes,most(upto25%ofalltesticulartumors)areteratocarcinomas,which
areacombinationofteratomaandembryonalcellcarcinoma.Upto6%ofalltesticulartumorsareofmixed
celltype,withseminomabeingoneofthecomponents.Treatmentforthesemixturesofseminomaand
NSGCTissimilartothatofNSGCTalone.
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CarcinomaInSitu

Inaseriesof250patientswithunilateraltesticularcancer,Berthelsenetal(1982)demonstratedthepresence
ofcarcinomainsitu(CIS)in13(5.2%)ofthecontralateraltestes.Thisisapproximatelytwicetheoverall
incidenceofbilateraltesticularcancer.Thepresenceofcontralateralatrophyorultrasonographicmicrolithiasis
inpatientswithtesticulartumorswarrantscontralateralbiopsy.Ifdiagnosed,CISisusuallytreatedbyexternal
beamradiationtherapy.
PatternsofMetastaticSpread
Withtheexceptionofchoriocarcinoma,whichdemonstratesearlyhematogenousspread,germcelltumorsof
thetestistypicallyspreadinastepwiselymphaticfashion.LymphnodesofthetestisextendfromT1toL4but
areconcentratedattheleveloftherenalhilumbecauseoftheircommonembryologicoriginwiththekidney.
Theprimarylandingsitefortherighttestisistheinteraortocavalareaattheleveloftherightrenalhilum.
Stepwisespread,inorder,istotheprecaval,preaortic,paracaval,rightcommoniliac,andrightexternaliliac
lymphnodes.Theprimarylandingsiteforthelefttestisistheparaaorticareaattheleveloftheleftrenal
hilum.Stepwisespread,inorder,istothepreaortic,leftcommoniliac,andleftexternaliliaclymphnodes.In
theabsenceofdiseaseontheleftside,nocrossovermetastasestotherightsidehaveeverbeenidentified.
However,righttoleftcrossovermetastasesarecommon.Theseobservationshaveresultedinmodified
surgicaldissectionstopreserveejaculationinselectedpatients(seeSectionTreatment).
Certainfactorsmayaltertheprimarydrainageofatestisneoplasm.Invasionoftheepididymisorspermatic
cordmayallowspreadtothedistalexternaliliacandobturatorlymphnodes.Scrotalviolationorinvasionof
thetunicaalbugineamayresultininguinalmetastases.Althoughtheretroperitoneumisthemostcommonly
involvedsiteinmetastaticdisease,visceralmetastasesmaybeseeninadvanceddisease.Thesitesinvolvedin
decreasingfrequencyincludelung,liver,brain,bone,kidney,adrenal,gastrointestinaltract,andspleen.As
mentionedpreviously,choriocarcinomaistheexceptiontotheruleandischaracterizedbyearlyhematogenous
spread,especiallytothelung.Choriocarcinomahasalsoapredilectionforunusualsitesofmetastasissuchas
thespleen.
ClinicalStaging
Manyclinicalstagingsystemshavebeenproposedfortesticularcancer.However,mostarevariationsofthe
originalsystemproposedbyBodenandGibb(1951).Inthissystem,astageAlesionwasconfinedtothe
testis,stageBdemonstratedregionallymphnodespread,andstageCwasspreadbeyondretroperitoneal
lymphnodes.Numerousclinicalstagingsystemshavealsobeensuggestedforseminoma.AstageIlesionis
confinedtothetestis.StageIIhasretroperitonealnodalinvolvement(IIAis<2cm,IIBis>2cm).StageIIIhas
supradiaphragmaticnodalinvolvementorvisceralinvolvement.TheTNMclassificationofAmericanJoint
Committee(2010)hasattemptedtostandardizeclinicalstagesasinTable241.
Table241.TNMClassificationofTumorsoftheTestis.
TPrimarytumor
TX: Cannotbeassessed
T0:

Noevidenceofprimarytumor

Tis: Intratubularcancer(CIS)
T1:

Limitedtotestisandepididymis,novascularinvasion

T2:

Invadesbeyondtunicaalbugineaandintotunicavaginalisorhasvascularinvasion

T3:

Invadesspermaticcord
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T4: Invadesscrotum
NRegionallymphnodes
NX: Cannotbeassessed
N0: Noregionallymphnodemetastasis
N1: Lymphnodemetastasis2cm,ormultiplenodes,none>2cmand<6nodespositive
N2: Nodalmass>2cmand5cmor6nodespositive
N3: Nodalmass>5cm
MDistantmetastasis
MX: Cannotbeassessed
M0: Nodistantmetastasis
M1a: Distantmetastasispresentinnonregionallymphnodesorlungs
M1b: Nonpulmonaryvisceralmetastases
SSerumtumormarkers
SX: Markersnotavailable
S0:

Markerlevelswithinnormallimits

S1:

Lacticaciddehydrogenase(LDH)<1.5normalandhCG<5000mIU/mLandAFP<1000ng/mL

S2:

LDH1.510normalorhCG500050,000mIU/mLorAFP100010,000ng/mL

S3:

LDH>10normalorhCG>50,000mIU/mLorAFP>10,000ng/mL

Source:AmericanJointCommitteeonCancer:CancerStagingManual,7thed.SpringerVerlag,NewYork,
2010.
ClinicalFindings
Symptoms

Themostcommonsymptomoftesticularcancerisapainlessenlargementofthetestis.Enlargementisusually
gradual,andasensationoftesticularheavinessisnotunusual.Thetypicaldelayintreatmentfrominitial
recognitionofthelesionbythepatienttodefinitivetherapy(orchiectomy)rangesfrom3to6months.The
lengthofdelaycorrelateswiththeincidenceofmetastases.Theimportanceofpatientawarenessandself
examinationisapparent.Acutetesticularpainisseeninapproximately10%ofcasesandmaybetheresultof
intratesticularhemorrhageorinfarction.
Approximately10%ofpatientspresentwithsymptomsrelatedtometastaticdisease.Backpain
(retroperitonealmetastasesinvolvingnerveroots)isthemostcommonsymptom.Othersymptomsinclude
coughordyspnea(pulmonarymetastases)anorexia,nausea,orvomiting(retroduodenalmetastases)bone
pain(skeletalmetastases)andlowerextremityswelling(venacavalobstruction).
Approximately10%ofpatientsareasymptomaticatpresentation,andthetumormaybedetectedincidentally
followingtrauma,oritmaybedetectedbythepatient'ssexualpartner.

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Signs

Atesticularmassordiffuseenlargementisfoundinmostcases.Themassistypicallyfirmandnontenderand
theepididymisshouldbeeasilyseparablefromit.Ahydrocelemayaccompanythetesticulartumorandhelp
tocamouflageit.Transilluminationofthescrotumcanhelptodistinguishbetweentheseentities.
Palpationoftheabdomenmayrevealbulkyretroperitonealdiseaseassessmentofsupraclavicular,scalene,and
inguinalnodesshouldbeperformed.Gynecomastiaispresentin5%ofallgermcelltumorsbutmaybepresent
in3050%ofSertoliandLeydigcelltumors.Itscauseseemstoberelatedtomultiplecomplexhormonal
interactionsinvolvingtestosterone,estrone,estradiol,prolactin,andhCG.Hemoptysismaybeseenin
advancedpulmonarydisease.
LaboratoryFindingsandTumorMarkers

Anemiamaybedetectedinadvanceddisease.Liverfunctiontestsmaybeelevatedinthepresenceofhepatic
metastases.Renalfunctionmaybediminished(elevatedserumcreatinine)ifureteralobstructionsecondaryto
bulkyretroperitonealdiseaseispresent.Theassessmentofrenalfunction(creatinineclearance)ismandatory
inpatientswithadvanceddiseasewhorequirechemotherapy.
Severalbiochemicalmarkersareofimportanceinthediagnosisandmanagementoftesticularcarcinoma,
includingAFP,hCG,andlacticaciddehydrogenase(LDH).AFPisaglycoproteinwithamolecularmassof
70,000daltonsandahalflifeof46days.Althoughpresentinfetalseruminhighlevels,beyondtheageof1
year,itispresentonlyintraceamounts.WhilepresenttovaryingdegreesinmanyNSGCTs(Table242),itis
neverfoundinseminomas.
Table242.IncidenceofElevatedTumorMarkersbyHistologicTypeinTestisCancer.
hCG(%) AFP(%)
Seminoma
7
0
Teratoma
25
38
Teratocarcinoma 57
64
Embryonal
60
70
Choriocarcinoma 100
0
AFP,alphafetoproteinhCG,humanchorionicgonadotropin.
hCGisaglycoproteinwithamolecularmassof38,000daltonsandahalflifeof24hours.Itiscomposedof
twosubunits:alphaandbeta.Thealphasubunitissimilartothealphasubunitsofluteinizinghormone(LH),
folliclestimulatinghormone(FSH),andthyroidstimulatinghormone(TSH).Thebetasubunitconveysthe
activitytoeachofthesehormonesandallowsforahighlysensitiveandspecificradioimmunoassayinthe
determinationofhCGlevels.AnormalmanshouldnothavesignificantlevelsofbetahCG.Whilemore
commonlyelevatedinNSGCTs,hCGlevelsmaybeelevatedinupto7%ofseminomas.
LDHisacellularenzymewithamolecularmassof134,000daltonsthathasfiveisoenzymesitisnormally
foundinmuscle(smooth,cardiac,skeletal),liver,kidney,andbrain.ElevationoftotalserumLDHandin
particularisoenzymeIwasshowntocorrelatewithtumorburdeninNSGCTs.LDHmayalsobeelevatedin
seminoma.
Othermarkershavebeendescribedfortestiscancer,includingplacentalalkalinephosphatase(PLAP)and
gammaglutamyltranspeptidase(GGT).Thesemarkers,however,havenotcontributedasmuchtothe
managementofpatientsasthosementionedpreviously.
Imaging
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Theprimarytesticulartumorcanberapidlyandaccuratelyassessedbyscrotalultrasonography.Thistechnique
candeterminewhetherthemassistrulyintratesticular,canbeusedtodistinguishthetumorfromepididymal
pathology,andmayalsofacilitatetesticularexaminationinthepresenceofahydrocele.
Oncethediagnosisoftesticularcancerhasbeenestablishedbyinguinalorchiectomy,carefulclinicalstaging
ofdiseaseismandatory.Chestradiographs(posteroanteriorandlateral)andcomputedtomography(CTscan)
oftheabdomenandpelvisareusedtoassessthetwomostcommonsitesofmetastaticspread,namely,the
lungsandretroperitoneum.TheroleofCTscanningofthechestremainscontroversialbecauseofitsdecreased
specificity.Ofnoteisthefactthatroutinechestxrays(CXR)detect8590%ofpulmonarymetastases.Pedal
lymphangiography(LAG)israrelyusedowingtoitsinvasivenessaswellaslowspecificity,althoughitmay
bewarrantedinpatientsundergoingasurveillanceprotocol(seeSectionTreatment).
DifferentialDiagnosis
Anincorrectdiagnosisismadeattheinitialexaminationinupto25%ofpatientswithtesticulartumorsand
mayresultindelayintreatmentorasuboptimalsurgicalapproach(scrotalincision)forexploration.
Epididymitisorepididymoorchitisisthemostcommonmisdiagnosisinpatientswithtestiscancer.Early
epididymitisshouldrevealanenlarged,tenderepididymisthatisclearlyseparablefromthetestis.Inadvanced
stages,theinflammationmayspreadtothetestisandresultinanenlarged,tender,andinduratedtestisand
epididymis.Ahistoryofacuteonsetofsymptomsincludingfever,urethraldischarge,andirritativevoiding
symptomsmaymakethediagnosisofepididymitismorelikely.Ultrasonographymayidentifytheenlarged
epididymisasthecauseofthescrotalmass.
Hydroceleisthesecondmostcommonmisdiagnosis.Transilluminationofthescrotummayreadilydistinguish
betweenatranslucent,fluidfilledhydrocele,andasolidtesticulartumor.Since510%oftesticulartumors
maybeassociatedwithhydroceles,ifthetestiscannotbeadequatelyexamined,ascrotalultrasound
examinationismandatory.Aspirationofthehydroceleshouldbeavoidedbecausepositivecytologicresults
havebeenreportedinhydrocelesassociatedwithtesticulartumors.
Otherdiagnosestobeconsideredincludespermatocele,acysticmassmostcommonlyfoundextendingfrom
theheadoftheepididymishematoceleassociatedwithtraumagranulomatousorchitis,mostcommonly
resultingfromtuberculosisandassociatedwithbeadingofthevasdeferensandvaricocele,whichis
engorgementofthepampiniformplexusofveinsinthespermaticcordandshoulddisappearwhenthepatient
isinthesupineposition.
Althoughmostintratesticularmassesaremalignant,onebenignlesion,anepidermoidcyst,maybeseenon
rareoccasions.Usually,thesecystsareverysmallbenignnoduleslocatedjustunderneaththetunicaalbuginea
however,onoccasion,theycanbelarge.Thediagnosisisusuallymadefollowinginguinalorchiectomyas
frozensections,thelargerlesionsareoftendifficulttodistinguishfromteratoma.
Treatment
Inguinalexplorationwithcrossclampingofthespermaticcordvasculatureanddeliveryofthetestisintothe
fieldisthemainstayofexplorationforapossibletestistumor.Ifcancercannotbeexcludedbyexaminationof
thetestis,radicalorchiectomyiswarranted.Scrotalapproachesandopentesticularbiopsiesshouldbeavoided.
Furthertherapydependsonthehistologiccharacteristicsofthetumoraswellastheclinicalstage.
LowStageSeminoma

Seminomaisexquisitelyradiosensitive.About95%ofallstageIseminomasarecuredwithradical
orchiectomyandretroperitonealirradiation(usually25003000cGy).Thislowdoseofradiationisusually
welltolerated,withminimalgastrointestinalsideeffects.Becauseradiationtherapyisassociatedwithsome
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morbidityandsecondarymalignancyrisk,thereisanincreasinginterestinsurveillanceinstageIseminoma.
Becauseoftheslowgrowthrateofseminoma,surveillancemustbeperformedforupto10yearsandtypically
consistsofahistoryandphysicalexamandtumormarkersevery34monthsforyears13,every6monthsfor
years47,andthenannuallyupto10years.ImagingwhileonsurveillanceincludesabdominalandpelvicCT
ateachvisitandCXRatalternatevisits.Alternatively,singleagentcarboplatinhasbeenusedinlowstage
seminoma(NCCN,2010).
Lowvolumeretroperitonealdiseasecanalsobetreatedeffectivelywithretroperitonealirradiationwithan
average5yearsurvivalrateof87%.Prophylacticmediastinalradiationisnolongeremployedbecausethis
maycauseconsiderablemyelosuppressionandthuscompromisethepatient'sabilitytoreceivechemotherapy
ifrequired.Chemotherapyshouldbeusedassalvagetherapyforpatientswhorelapsefollowingirradiation.
HighStageSeminoma

PatientswithbulkyseminomaandanyseminomaassociatedwithanelevatedAFPshouldreceiveprimary
chemotherapy.Seminomasarealsosensitivetoplatinumbasedregimens,asaretheirNSGCTcounterparts.
Goodriskpatients(seelater)receivefourcyclesofetoposideandcisplatin(EP)orthreecyclesofcisplatin,
etoposide,andbleomycin(PEB).IntermediateriskpatientsreceivefourcyclesofPEB.
Ninetypercentofpatientswithadvanceddiseaseachieveacompleteresponsewithchemotherapy.Residual
retroperitonealmassesfollowingchemotherapyareoftenfibrosis(90%)unlessthemassiswellcircumscribed
andinexcessof3cm,underwhichcircumstancesapproximately40%ofpatientsharborresidualseminoma.A
positronemissiontomography(PETscan)shouldbeperformedinpatientswitharesidualmassandifpositive,
surgicalresectioniswarranted.Insuchcases,surgicalexcisioniswarranted.
LowStageNonseminomatousGermCellTumors

StandardtreatmentforstageIdiseaseintheUnitedStateshasincludedretroperitoneallymphnodedissection
(RPLND).However,becausethreefourthsofpatientswithclinicalstageIdiseasearecuredbyorchiectomy
aloneandthemorbidityofRPLNDisnotnegligible,otheralternativeshavebeenexplored.Theseoptions
includesurveillanceandopennervesparingRPLND.
SurveillanceinstageINSGCTwasproposedbecause,asmentionedpreviously,75%ofpatientswithclinical
stageIdiseasehave,infact,pathologicstageIdisease.Inaddition,infertilityrelatedtodisruptionof
sympatheticnervefibersiscommonfollowingRPLND.Clinicalstaginghasbeenmarkedlyimprovedinthe
presenceofCTscanningandLAG.Andfinally,effectivechemotherapyregimenshavebeendevelopedfor
relapse.PatientsareconsideredcandidatesforsurveillanceifthetumorisanNSGCTconfinedwithinthe
tunicaalbuginea,thetumordoesnotdemonstratevascularinvasion,tumormarkersnormalizeafter
orchiectomy,radiographicimagingshowsnoevidenceofdisease(CXR,CT),andthepatientisconsidered
reliable.
Surveillanceshouldbeconsideredanactiveprocessonthepartofboththephysicianandthepatient.Patients
arefollowedevery12monthsforthefirst2years,every3monthsinyear3,every4monthsinyear4,and
every6monthsinyear5.TumormarkersandCXRareobtainedateachvisit,andCTscansareobtainedevery
23monthsinyear1,every34monthsinyear2,every4monthsinyear3,every6monthsinyear4,and
onceayearinyear5.Mostrelapsesoccur,however,withinthefirst810months.Withrareexceptions,
patientswhorelapsecanbecuredbychemotherapyorsurgery,orboth.
RetroperitoneallymphnodedissectionhasbeenthepreferredtreatmentoflowstageNSGCTsintheUnited
Statesuntilrecently.Athoracoabdominalormidlinetransabdominalapproachmaybeused,andallnodal
tissuebetweentheuretersfromtherenalvesselstothebifurcationofthecommoniliacvesselsisremoved.
PatientswithnegativenodesorN1diseasedonotrequireadjuvanttherapy,whereastherecommendationfor
thosewithN2diseaseistoreceivetwocyclesofchemotherapybecausetheirrelapserateapproaches50%.
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Whileeffectiveinsurgicallystagingandpotentiallycuringasubsetofpatients,RPLNDisassociatedwith
significantmorbidity,especiallywithrespecttofertilityinyoungmen.WithastandardRPLND,sympathetic
nervefibersaredisrupted,resultinginlossofseminalemission.Currently,amodifiedRPLNDcanbe
performedthatpreservesejaculationinupto90%ofpatients.Bymodifyingthedissectionbelowthelevelof
theinferiormesentericarterytoincludeonlythenodaltissueipsilateraltothetumor,importantsympathetic
fibersfromthecontralateralsidearepreserved,thusmaintainingemission.
AnalternativeapproachtopatientswithclinicalstageIdiseaseandvascularinvasionintheprimaryistwo
cyclesofchemotherapy.Whileobviatingtheneedforsurgery,suchanapproachisassociatedwith
neurotoxicityandfertilityissuesfortheseyoungpatients.
HighStageNonseminomatousGermCellTumors

Patientswithbulkyretroperitonealdisease(>3cmnodesorthreeormore1cmcutsonCTscan)ormetastatic
NSGCTaretreatedwithprimaryplatinumbasedcombinationchemotherapyfollowingorchiectomy.Good
riskpatientsaretreatedwitheitherfourcyclesofEPorthreecyclesofPEB.Intermediateandpoorrisk
patientsreceivefourcyclesofPEB.Iftumormarkersnormalizeandaresidualmassisapparentonimaging
studies,resectionofthatmassismandatory,because20%ofthetimeitwillharborresidualcancer,40%ofthe
timeitwillbeteratoma,and40%ofthetimeitwillbefibrosis(Figure242).Inpatientswithresidualcancer
intheresectedtissue,thehistologicpictureisusuallyembryonalcellcarcinoma,butmalignantteratomais
seenin<5%ofcases.Malignantteratomaisunresponsivetochemotherapy,andonly15%ofpatientssurvive
followingsurgicalresection.Iftumormarkersfailtonormalizefollowingprimarychemotherapy,salvage
chemotherapyisrequired(cisplatin,etoposide,bleomycin,ifosfamide).Evenifpatientsattainacomplete
responseafterchemotherapy(normaltumormarkers,nomassonCTscanorCXR),someinvestigators
advocateanRPLNDbecauseviablegermcelltumormaybeseeninupto10%ofcases.
Figure242.

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Upper:Computedtomographyscanofpatientwithbulkyretroperitonealmassafterradicalorchiectomyfor
embryonalcarcinoma.Lower:Residualcysticmassafterchemotherapyitwasresectedandfoundtobe
teratoma.
Althoughthetreatmentplandescribedcuresupto70%ofpatientswithhighvolumedisease,therearepatients
whofailtorespond.Also,thepotentialcomplicationsfromchemotherapyincludingsepsis,neuropathy,renal
toxicity,anddeathmustbeconsidered.Itisthusapparentthatitisimportanttobeabletodiscriminate
betweenpatientswhoarelikelytorespondtostandardchemotherapy(goodrisk)andthosewhomayrequire
moreaggressiveregimens(intermediateorhighrisk).Table243stratifiespatientswithadvancedtesticular
cancerintoriskgroupsbasedupontheprimarytumorsite,locationofmetastases,andserumtumormarkers.
Therateofdeclineofserumtumormarkersduringchemotherapyhasalsobeenusedtopredictresponsein
patientswithadvanceddisease.
Table243.RiskClassificationforTesticularCancer.
Riskstatus
Nonseminoma
Seminoma
Testicularorretroperitonealprimary Anyprimarysite

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Testicularorretroperitonealprimary Anyprimarysite
Goodrisk

Nononpulmonaryvisceralmetastases Nononpulmonaryvisceralmetastases
PostorchiectomymarkersS1level
NormalAFP,anyhCG,anyLDH
Testicularorretroperitonealprimary Anyprimarysite

Intermediaterisk Nononpulmonaryvisceralmetastases Nononpulmonaryvisceralmetastases

Poorrisk

PostorchiectomymarkersS2level
Mediastinalprimarytumor

NormalAFP,anyhCG,anyLDH

Nonpulmonaryvisceralmetastases

None

PostorchiectomymarkersS3level
AFP,alphafetoproteinhCG,humanchorionicgonadotropinLDH,lacticaciddehydrogenase.
FollowUpCare
Allpatientswithtesticularcancerrequireregularfollowupcare.Asdiscussedpreviously,patientsona
surveillanceprotocolrequirevigorousfollowup.Forthosewhohaveundergonesurgery(RPLND)or
radiotherapy,ingeneral,theyarefollowedat3monthintervalsforthefirst2years,thenevery6monthsuntil
5years,andthenyearly.Followupvisitsshouldincludecarefulexaminationoftheremainingtestis,the
abdomen,andthelymphnodeareas.LaboratoryinvestigationshouldincludeAFP,hCG,andLDHlevels.A
CXRandanabdominalfilm(ifanLAGwasperformed)shouldalsobeincludedateachvisit.AbdominalCT
scansareusedlessfrequentlyasriskofrelapseintheretroperitoneumislowfollowingRPLND.
Prognosis
Survivalintesticularcancerhasimproveddramaticallyoverthepastseveralyears,reflectingthecontinuing
improvementandrefinementincombinationchemotherapy.Forseminomatreatedbyorchiectomyand
radiotherapy,the5yeardiseasefreesurvivalrateis98%forstageIand9294%forstageIIAinseveral
recentseries.Higherstagediseasetreatedbyorchiectomyandprimarychemotherapyhasa5yeardiseasefree
survivalrateof3575%,yetthelowervaluecomesfromolderseriesinwhichmorecrudechemotherapy
regimenswereemployed.
SurvivalinpatientswithNSGCTstreatedbyorchiectomyandRPLNDforstageIdiseaserangesfrom96%to
100%.ForlowvolumestageIIdiseasetreatedwithchemotherapyplussurgery,>90%5yeardiseasefree
survivalratesareattainable.Patientswithbulkyretroperitonealordisseminateddiseasetreatedwithprimary
chemotherapyfollowedbysurgeryhavea5yeardiseasefreesurvivalrateof5580%.

NonGermCellTumorsoftheTestis
Approximately56%ofalltestistumorsarenongermcelltumorsofthetestis.Threetypeswillbe
considered,namely,Leydigcelltumors,Sertolicelltumors,andgonadoblastomas.

LeydigCellTumors
EpidemiologyandPathology
Leydigcelltumorsarethemostcommonnongermcelltumorsofthetestisandaccountfor13%ofall
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testiculartumors.Theyfollowabimodalagedistribution:the5to9yearoldandthe25to35yearoldage
groups.Twentyfivepercentofthesetumorsoccurinchildhood.Bilateralityisseenin510%ofcases.The
causeofthesetumorsisunknownunlikegermcelltumors,thereisnoassociationwithcryptorchidism.
Pathologicexaminationrevealsasmall,yellow,wellcircumscribedlesiondevoidofhemorrhageornecrosis.
Microscopically,hexagonallyshapedcellswithgranular,eosinophiliccytoplasmcontaininglipidvacuolesare
seen.ReinkecrystalsarefusiformshapedcytoplasmicinclusionsthatarepathognomonicforLeydigcells.
ClinicalFindings
Prepubertalchildrenusuallypresentwithvirilization,andtumorsarebenign.Adultsareusuallyasymptomatic,
althoughgynecomastiamaybepresentin2025%.Tenpercentoftumorsinadultsaremalignant.Laboratory
findingsincludeelevatedserumandurinary17ketosteroidsaswellasestrogens.
TreatmentandPrognosis
RadicalorchiectomyistheinitialtreatmentforLeydigcelltumors.Clinicalstagingissimilartothatforgerm
celltumors,andlevelsofthe17ketosteroidscanbehelpfulindistinguishingbetweenbenignandmalignant
lesions.Elevationsof1030timesnormalaretypicalofmalignancy.RPLNDisrecommendedformalignant
lesions.Becauseoftherarityoftheselesions,theroleofchemotherapyremainstobedefined.Prognosisis
excellentforbenignlesions,whileitremainspoorforpatientswithdisseminateddisease.

SertoliCellTumors
EpidemiologyandPathology
Sertolicelltumorsareexceedinglyrare,composing<1%ofalltesticulartumors.Abimodalagedistributionis
seen:1yearoldoryoungerandthe20to45yearoldagegroup.Approximately10%ofthelesionsare
malignant.Grossexaminationrevealsayelloworgraywhitelesionwithcysticcomponents.Benignlesions
arewellcircumscribed,whilemalignantlesionsshowilldefinedborders.Microscopically,tumorsappear
heterogeneouswithmixedamountsofepithelialandstromalcomponents.Sertolicellsarecolumnaror
hexagonalcellswithalargenucleusandsolitarynucleolusandcontainvacuolatedcytoplasm.
ClinicalFindings
Atesticularmassisthemostcommonpresentation.Virilizationisoftenseeninchildren,andgynecomastia
maybepresentin30%ofadults.Becauseoftherarityofthesetumors,minimalendocrinedataareavailable
onthesepatients.
Treatment
Radicalorchiectomyistheinitialprocedureofchoice.Incasesofmalignancy,RPLNDisindicatedhowever,
therolesofchemotherapyandradiotherapyremainunclear.

Gonadoblastomas
EpidemiologyandPathology
Gonadoblastomascomprise0.5%ofalltesticulartumorsandarealmostexclusivelyseeninpatientswithsome
formofgonadaldysgenesis.Mostofthesetumorsoccurinpatientsyoungerthan30years,althoughtheage
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distributionrangesfrominfancyto>70years.Grossexaminationrevealsayelloworgraywhitelesionthat
canvaryinsizefrommicroscopicto>20cmandmayexhibitcalcifications.Microscopically,threecelltypes
areseen:Sertolicells,interstitialcells,andgermcells.
ClinicalFindings
Theclinicalmanifestationsarepredominantlyrelatedtotheunderlyinggonadaldysgenesisandarediscussed
elsewhereinthisbook.Itisnoteworthythatfourfifthsofpatientswithgonadoblastomasarephenotypic
females.Malestypicallyhavecryptorchidismorhypospadias.
TreatmentandPrognosis
Radicalorchiectomyistheprimarytreatmentofchoice.Inthepresenceofgonadaldysgenesis,acontralateral
gonadectomyisrecommendedbecausethetumortendstobebilateralin50%ofcasesinthissetting.Prognosis
isexcellent.

SecondaryTumorsoftheTestis
Secondarytumorsofthetestisarerare.Threecategoriesareconsidered:lymphoma,leukemia,andmetastatic
tumors.

Lymphoma
EpidemiologyandPathology
Lymphomaisthemostcommontesticulartumorinapatientolderthan50yearsandisthemostcommon
secondaryneoplasmofthetestis,accountingfor5%ofalltesticulartumors.Itmaybeseeninthreeclinical
settings:(1)latemanifestationofwidespreadlymphoma(2)initialpresentationofclinicallyoccultdisease
and(3)primaryextranodaldisease.Grossexaminationrevealsabulging,grayorpinklesionwithilldefined
margins.Hemorrhageandnecrosisarecommon.Microscopically,diffusehistiocyticlymphomaisthemost
commontype.
ClinicalFindings
Painlessenlargementofthetestisiscommon.Generalizedconstitutionalsymptomsoccurinonefourthof
patients.Bilateraltestisinvolvementoccursin50%ofpatients,usuallyasynchronously.
TreatmentandPrognosis
Fineneedleaspirationshouldbeconsideredinpatientswithaknownorsuspecteddiagnosisoflymphoma
whileradicalorchiectomyisreservedforthosewithsuspectedprimarylymphomaofthetesticle.Further
stagingandtreatmentshouldbehandledinconjunctionwiththemedicaloncologist.Prognosisisrelatedtothe
stageofdisease.Somereportssupportadjuvantchemotherapyforprimarytesticularlymphoma,with
improvedsurvivalratesofupto93%after44monthsoffollowup.

LeukemicInfiltrationoftheTestis
Thetestisisacommonsiteofrelapseforchildrenwithacutelymphocyticleukemia.Bilateralinvolvement
maybepresentinonehalfofcases.Testisbiopsyratherthanorchiectomyisthediagnosticprocedureof
choice.Bilateraltesticularirradiationwith20Gyandreinstitutionofadjuvantchemotherapyconstitutethe
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treatmentofchoice.Prognosisremainsguarded.

MetastaticTumors
Metastasistothetestisisrare.Theselesionsaretypicallyincidentalfindingsatautopsy.Themostcommon
primarysiteistheprostate,followedbythelung,gastrointestinaltract,melanoma,andkidney.Thetypical
pathologicfindingisneoplasticcellsintheinterstitiumwithrelativesparingoftheseminiferoustubules.

ExtragonadalGermCellTumors
EpidemiologyandPathology
Extragonadalgermcelltumorsarerare,accountingforapproximately3%ofallgermcelltumors.Debate
continuesoverwhethertheselesionsoriginatefromburnedouttesticularprimariesororiginatedenovo.
Mostretroperitonealtumorshavetheiroriginfromatesticularprimary,whereasmediastinalgermcelltumors
aretrulyectopic.
Themostcommonsitesoforiginindecreasingorderaremediastinum,retroperitoneum,sacrococcygealarea,
andpinealgland.Allgermcelltypesmaybeobserved.Seminomacomposesmorethanhalfofthe
retroperitonealandmediastinaltumors.
ClinicalFindings
Clinicalpresentationdependsonthesiteandvolumeofdisease.Mediastinallesionsmaypresentwith
pulmonarycomplaints.Retroperitoneallesionsmaypresentwithabdominalorbackpainandapalpablemass.
Sacrococcygealtumorsaremostcommonlyseeninneonatesandmaypresentwithapalpablemassandbowel
orurinaryobstruction.Pinealtumorsmaypresentwithheadache,visualorauditorycomplaints,or
hypopituitarism.
Metastaticspreadistoregionallymphnodes,lung,liver,bone,andbrain.Metastaticworkupissimilar,
therefore,tothatoftesticulargermcelltumors.Acarefultesticularexaminationismandatoryalongwith
ultrasonographytoexcludeanocculttesticularprimary.
TreatmentandPrognosis
Treatmentofextragonadalgermcelltumorsparallelsthatoftesticulartumors.Lowvolumeseminomacanbe
managedwithradiotherapy.Highvolumeseminomashouldreceiveprimarychemotherapy.Prognosisparallels
thatoftesticularseminoma.Primarychemotherapyshouldbeemployedfornonseminomatouselementswith
surgicalexcisionofresidualmasseshowever,prognosisremainspoorforthesepatients.

TumorsoftheEpididymis,ParatesticularTissues,andSpermaticCord
Primarytumorsoftheepididymisarerareandaremostcommonlybenign.Adenomatoidtumorsofthe
epididymisarethemostcommonandtypicallyoccurinthethirdandfourthdecadeoflife.Theyaretypically
asymptomatic,solidlesionsthatarisefromanyportionoftheepididymis.
Leiomyomasarethesecondmostcommontumoroftheepididymis.Theselesionstendtobepainfulandare
oftenassociatedwithahydrocele.Cystadenomasarebenignlesionsoftheepididymisthatarebilateralin30%
ofcasesandarefrequentlyseeninassociationwithvonHippelLindaudisease.Histologically,theselesions
aredifficulttodistinguishfromrenalcellcarcinoma.Malignantlesionsoftheepididymisareextremelyrare.
Ingeneral,aninguinalapproachshouldbeused,andiffrozensectionconfirmsabenignlesion,
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epididymectomyshouldbeperformed.Ifamalignanttumorisdiagnosed,radicalorchiectomymustbe
performed.
Tumorsofthespermaticcordaretypicallybenign.Lipomasofthecordaccountformostoftheselesions.Of
themalignantlesions,rhabdomyosarcomaisthemostcommon,followedbyleiomyosarcoma,fibrosarcoma,
andliposarcoma.
Clinicaldiagnosisoftumorsofthespermaticcordcanbedifficult.Differentiatingbetweenaherniaanda
spermaticcordtumormaybepossibleonlyatexploration.Ingeneral,theselesionsshouldbeapproached
throughaninguinalincision.Thecordshouldbeoccludedattheinternalringandfrozensectionsobtained.If
malignancyisdiagnosed,attentionshouldbedirectedtowardperformingwidelocalexcisiontoavoidlocal
recurrence.Stagingofdiseaseissimilartothatoftesticulartumors.Forrhabdomyosarcoma,RPLNDshould
beperformedwithadjuvantradiotherapyandchemotherapy.ThevalueofRPLNDfortheothermalignant
spermaticcordtumorsremainstobedetermined.Prognosisrelatestothehistologicstatus,stage,andsiteof
disease.

TumorsofthePenis
EpidemiologyandRiskFactors
Carcinomaofthepenisaccountsfor<1%ofcancersamongmalesintheUnitedStates,withapproximately
onetotwonewcasesbeingreportedper100,000men.Thereismarkedvariationinincidencewithgeographic
location.InareassuchasAfricaandregionsofSouthAmerica,penilecarcinomamaycompose1020%ofall
malignantlesions.Penilecarcinomaoccursmostcommonlyinthesixthdecadeoflife,althoughrarecase
reportshaveincludedchildren.
Theoneetiologicfactormostcommonlyassociatedwithpenilecarcinomaispoorhygiene.Thediseaseis
virtuallyunheardofinmalescircumcisednearbirth.Onetheorypostulatesthatsmegmaaccumulationunder
thephimoticforeskinresultsinchronicinflammationleadingtocarcinoma.Aviralcausehasalsobeen
suggestedasaresultoftheassociationofthistumorwithcervicalcarcinoma.
Pathology
PrecancerousDermatologicLesions

Leukoplakiaisarareconditionthatmostcommonlyoccursindiabeticpatients.Awhiteplaquetypically
involvingthemeatusisseen.Histologicexaminationrevealsacanthosis,hyperkeratosis,andparakeratosis.
Thislesionmayprecedeoroccursimultaneouslywithpenilecarcinoma.
Balanitisxeroticaobliteransisawhitepatchoriginatingontheprepuceorglansandusuallyinvolvingthe
meatus.Theconditionismostcommonlyobservedinmiddleageddiabeticpatients.Microscopicexamination
revealsatrophicepidermisandabnormalitiesincollagendeposition.
Giantcondylomataacuminataarecauliflowerlikelesionsarisingfromtheprepuceorglans.Thecauseis
believedtobeviral(humanpapillomavirus).Theselesionsmaybedifficulttodistinguishfromwell
differentiatedsquamouscellcarcinoma.
CarcinomaInSitu(BowenDisease,ErythroplasiaofQueyrat)

Bowendiseaseisasquamouscellcarcinomainsitutypicallyinvolvingthepenileshaft.Thelesionappearsas
aredplaquewithencrustations.
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ErythroplasiaofQueyratisavelvety,redlesionwithulcerationsthatusuallyinvolvetheglans.Microscopic
examinationshowstypical,hyperplasticcellsinadisorderedarraywithvacuolatedcytoplasmandmitotic
figures.
InvasiveCarcinomaofthePenis

Squamouscellcarcinomacomposesmostpenilecancers.Itmostcommonlyoriginatesontheglans,withthe
nextmostcommonsites,inorder,beingtheprepuceandshaft.Theappearancemaybepapillaryorulcerative.
Verrucouscarcinomaisavariantofsquamouscellcarcinomacomposing516%ofpenilecarcinomas.This
lesionispapillaryinappearance,andonhistologicexamination,itisnotedtohaveawelldemarcateddeep
marginunliketheinfiltratingmarginofthetypicalsquamouscellcarcinoma.
PatternsofSpread
Invasivecarcinomaofthepenisbeginsasanulcerativeorpapillarylesion,whichmaygraduallygrowto
involvetheentireglansorshaftofthepenis.Buck'sfasciarepresentsabarriertocorporalinvasionand
hematogenousspread.Primarydisseminationisvialymphaticchannelstothefemoralandiliacnodes.The
prepuceandshaftskindrainintothesuperficialinguinalnodes(superficialtofascialata),whiletheglansand
corporalbodiesdraintobothsuperficialanddeepinguinalnodes(deeptofascialata).Therearemanycross
communicationssothatpenilelymphaticdrainageisbilateraltobothinguinalareas.Drainagefromthe
inguinalnodesistothepelvicnodes.Involvementofthefemoralnodesmayresultinskinnecrosisand
infectionorfemoralvesselerosionandhemorrhage.Distantmetastasesareclinicallyapparentin<10%of
casesandmayinvolvelung,liver,bone,orbrain.
TumorStaging
ThestagingsystemusedmostcommonlyintheUnitedStateswasproposedbyJackson(1966),andthestages
areasfollows:InstageI,thetumorisconfinedtotheglansorprepuce.StageIIinvolvesthepenileshaft.
StageIIIhasoperableinguinalnodemetastasis.InstageIV,thetumorextendsbeyondthepenileshaft,with
inoperableinguinalordistantmetastases.TheTNMclassificationoftheAmericanJointCommittee(1996)is
giveninTable244.
Table244.TNMClassificationofTumorsofthePenis.
TPrimarytumor
TX: Cannotbeassessed
T0: Noevidenceofprimarytumor
Tis: Carcinomainsitu
Ta: Noninvasiveverrucouscarcinoma
T1: Invadessubepithelialconnectivetissue
T2: Invadescorpusspongiosumorcavernosum
T3: Invadesurethraorprostate
T4: Invadesotheradjacentstructures
NRegionallymphnodes
NX: Cannotbeassessed
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N0: Noregionallymphnodemetastasis
N1: Metastasisinsinglesuperficialinguinalnode
N2: Metastasisinmultipleorbilateralsuperficialinguinalnodes
N3: Metastasisindeepinguinalorpelvicnodes
MDistantmetastasis
MX: Cannotbeassessed
M0: Nodistantmetastasis
M1: Distantmetastasispresent
Source:AmericanJointCommitteeonCancer:TNMClassificationGenitourinarySites,2010.
ClinicalFindings
Symptoms

Themostcommoncomplaintatpresentationisthelesionitself.Itmayappearasanareaofindurationor
erythema,anulceration,asmallnodule,oranexophyticgrowth.Phimosismayobscurethelesionandresultin
adelayinseekingmedicalattention.Infact,1550%ofpatientsdelayforatleast1yearinseekingmedical
attention.Othersymptomsincludepain,discharge,irritativevoidingsymptoms,andbleeding.
Signs

Lesionsaretypicallyconfinedtothepenisatpresentation.Theprimarylesionshouldbecharacterizedwith
respecttosize,location,andpotentialcorporalbodyinvolvement.Carefulpalpationoftheinguinalareais
mandatorybecause>50%ofpatientspresentwithenlargedinguinalnodes.Thisenlargementmaybe
secondarytoinflammationormetastaticspread.
LaboratoryFindings

Laboratoryevaluationistypicallynormal.Anemiaandleukocytosismaybepresentinpatientswithlong
standingdiseaseorextensivelocalinfection.Hypercalcemiaintheabsenceofosseousmetastasesmaybeseen
in20%ofpatientsandappearstocorrelatewithvolumeofdisease.
Imaging

MetastaticworkupshouldincludeCXR,bonescan,andCTscanoftheabdomenandpelvis.Disseminated
diseaseispresentin<10%ofpatientsatpresentation.
DifferentialDiagnosis
Inadditiontothedermatologiclesionsdiscussedpreviously,carcinomaofthepenismustbedifferentiated
fromseveralinfectiouslesions.Syphiliticchancremaypresentasapainlessulceration.Serologicanddark
fieldexaminationshouldestablishthediagnosis.Chancroidtypicallyappearsasapainfululcerationofthe
penis.SelectiveculturesforHaemophilusducreyishouldidentifythecause.Condylomataacuminataappearas
exophytic,soft,grapeclusterlesionsanywhereonthepenileshaftorglans.Biopsycandistinguishthis
lesionfromcarcinomaifanydoubtexists.
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Treatment
PrimaryLesion

Biopsyoftheprimarylesionismandatorytoestablishthediagnosisofmalignancy.Treatmentvaries
dependingonthepathologyaswellasthelocationofthelesion.CISmaybetreatedconservativelyinreliable
patients.Fluorouracilcreamapplicationorneodymium:YAGlasertreatmentiseffectiveforCISandis
preservingofthepenis.Patientsmustcomeforfrequentfollowupexaminationstomonitorresponse.
Thegoaloftreatmentininvasivepenilecarcinomaiscompleteexcisionwithadequatemargins.Forlesions
involvingtheprepuce,thismaybeaccomplishedbysimplecircumcision.Forlesionsinvolvingtheglansor
distalshaft,partialpenectomywitha2cmmargintodecreaselocalrecurrencehastraditionallybeen
suggested.LessaggressivesurgicalresectionssuchasMohsmicrographicsurgeryandlocalexcisionsdirected
atpenilepreservationyetattaininganegativesurgicalmarginhavegainedpopularity.Forlesionsinvolvingthe
proximalshaftorwhenpartialpenectomyresultsinapenilestumpofinsufficientlengthforsexualfunctionor
directingtheurinarystream,totalpenectomywithperinealurethrostomyhasbeenrecommended.
RegionalLymphNodes

Asdiscussedpreviously,penilecarcinomaspreadsprimarilytotheinguinallymphnodes.However,
enlargementofinguinalnodesatpresentationdoesnotnecessarilyimplymetastaticdisease.Infact,upto50%
ofthetimethisenlargementiscausedbyinflammation.Thus,patientswhopresentwithenlargedinguinal
nodesshouldundergotreatmentoftheprimarylesionfollowedbya4to6weekcourseoforalbroad
spectrumantibiotics.Persistentadenopathyfollowingantibiotictreatmentshouldbeconsideredtobe
metastaticdisease,andsequentialbilateralilioinguinalnodedissectionsshouldbeperformed.If
lymphadenopathyresolveswithantibiotics,observationinlowstageprimarytumors(Tis,T1)iswarranted.
However,iflymphadenopathyresolvesinhigherstagetumors,morelimitedlymphnodesamplingsshouldbe
considered,suchasthesentinelnodebiopsydescribedbyCabanas(1977)oramodified(limited)dissectionas
suggestedbyCatalona(1988)(Figure243).Ifpositivenodesareencountered,bilateralilioinguinalnode
dissectionshouldbeperformed.AdecisiontreeforpenilecarcinomaispresentedinFigure244.Patientswho
initiallyhaveclinicallynegativenodesbutinwhomclinicallypalpablenodeslaterdevelopshouldundergoa
unilateralilioinguinalnodedissection.
Figure243.

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Comparisonoflimitsofdissectionofcomplete(dashedline)versuslimited(solidline)inguinal
lymphadenectomy.
Figure244.

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Managementofpenilecarcinoma.
Patientswhohaveinoperablediseaseandbulkyinguinalmetastasesaretreatedwithchemotherapy(cisplatin
and5fluorouracil).Insomecases,regionalradiotherapycanprovidesignificantpalliationbydelaying
ulcerationandinfectiouscomplicationsandalleviatingpain.
SystemicDisease

Fourchemotherapeuticagentsdemonstrateactivityagainstpenilecarcinoma:bleomycin,methotrexate,
cisplatin,and5fluorouracil.However,nolongtermrespondershavebeenreported.
Prognosis
Survivalinpenilecarcinomacorrelateswiththepresenceorabsenceofnodaldisease.Fiveyearsurvivalrates
forpatientswithnodenegativediseaserangefrom65%to90%.Forpatientswithpositiveinguinalnodes,this
ratedecreasesto3050%andwithpositiveiliacnodesdecreasesto<20%.Inthepresenceofsofttissueor
bonymetastases,no5yearsurvivorshavebeenreported.
OtherPenileTumors
Squamouscellcarcinomaaccountsfor98%ofpenilecancers.Sporadiccasesofmelanoma,basalcell
carcinoma,andPagetdiseasehavebeenreported.TheincidenceofKaposisarcomaofthepenisisincreasing
withtheincreasingprevalenceofthehumanimmunodeficiencyvirus.Itappearsasapainfulpapuleonthe
glansorshaftwithbluishpurplediscoloration.Theselesionstendtoberadiosensitive.

TumorsoftheScrotum
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Tumorsofthescrotalskinarerare.Themostcommonbenignlesionisasebaceouscyst.Squamouscell
carcinomaisthemostcommonmalignanttumorofthescrotum,althoughrarecasesofmelanoma,basalcell
carcinoma,andKaposisarcomahavebeenreported.Inthepast,squamouscellcarcinomaofthescrotummost
commonlyresultedfromexposuretoenvironmentalcarcinogensincludingchimneysoot,tars,paraffin,and
somepetroleumproducts.Today,mostcasesresultfrompoorhygieneandchronicinflammation.
Biopsyofthescrotallesionmustbeperformedtoestablishahistologicdiagnosis.Wideexcisionwitha2cm
marginshouldbeperformedformalignanttumors.Surroundingsubcutaneoustissueshouldbeexcisedwith
theprimarytumorhowever,resectionofthescrotalcontentsisrarelynecessary.Primaryclosureusingthe
redundantscrotalskinisusuallypossible.Themanagementofinguinalnodesshouldbesimilartothatof
penilecancer.
Prognosiscorrelateswiththepresenceorabsenceofnodalinvolvement.Inthepresenceofinguinalnode
metastasis,the5yearsurvivalrateisapproximately25%therearevirtuallynosurvivorsifiliacnodesare
involved.

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TumorsofthePenis
CabanasRM:Anapproachforthetreatmentofpenilecarcinoma.Cancer197739:456.[PubMed:837331]
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McGrawHill
CopyrightMcGrawHillGlobalEducationHoldings,LLC.
Allrightsreserved.
YourIPaddressis189.149.255.191
AccessProvidedby:UniversidadAutonomadeYucatan
Silverchair
Tumorigenicmodelforgermcelltumorsofthetestis.
Upper:Computedtomographyscanofpatientwithbulkyretroperitonealmassafterradicalorchiectomyfor
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embryonalcarcinoma.Lower:Residualcysticmassafterchemotherapyitwasresectedandfoundtobe
teratoma.
Comparisonoflimitsofdissectionofcomplete(dashedline)versuslimited(solidline)inguinal
lymphadenectomy.
Managementofpenilecarcinoma.

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