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MalignantMelanomaWorkup
WORKUP

ApproachConsiderations
Thediagnosisofmelanomaisconfirmedbyexcisionalbiopsy.Patientswithclinicallyenlargedlymph
nodesandnoevidenceofdistantdiseaseshouldundergoacompleteregionallymphnodedissection.
Sentinellymphnodebiopsyisappropriateinselectedpatients.
Laboratorystudiesthatareindicatedincludethefollowing:
Completebloodcellcount(CBC)
Comprehensiveserumchemistrypanel
Lactatedehydrogenase(LDH)level
Imagingstudiesareoftenobtainedinpatientswithnewlydiagnosedmelanoma,toruleoutclinically
occultdistantdisease.Nevertheless,availableevidencesuggeststhatpreoperativeimagingstudies
havesignificantcostsandofferminimalbenefitinmostpatientswithmelanoma.[14]Onemeta
analysisofdiagnostictestsusedinstagingmelanomahasshownthatultrasonographyisthebest
imagingstudytodiagnoselymphnodeinvolvementandthatpositronemissiontomographycomputed
tomographyscanning(PET/CT)isthebestimagingstudytolookforothersitesofmetastasis.[15]

HistologicFindings
Althoughnosinglehistologicfeatureispathognomonicformelanoma,manycharacteristicfeatures
exist.Cytologicatypiavirtuallyalwaysisnoted,withenlargedcellscontaininglarge,pleomorphic,
hyperchromicnucleiwithprominentnucleoli.Numerousmitoticfiguresoftenarenoted.
Apagetoidgrowthpatternwithupwardgrowthofthemelanocytes,sotheyarenolongerconfinedto
thebasallayer,isconsideredpathognomonicformelanomabysomepathologists.
Althoughimmunohistochemicalstainsusuallyarenotnecessaryfordiagnosis,theyaregenerally
performedforcompleteness.BothS100andhomatropinemethylbromide(HMB45)stainsarepositive
inmelanoma.TheS100ishighlysensitive,althoughnotspecific,formelanoma,whiletheHMB45is
highlyspecificandmoderatelysensitiveformelanoma.The2stains,inconcert,canbeusefulin
diagnosingpoorlydifferentiatedmelanomas.

CompleteChemistryPanel
Thechemistrypanelmaygiveacluetopossiblemetastaticdisease.Forexample,anelevated
alkalinephosphataselevelmaysignalmetastasistotheboneorliver,whileelevatedlevelsonliver
functiontests(aspartateaminotransferase[AST],alanineaminotransferase[ALT])mayrepresent
metastasistotheliver.

Totalproteinandalbuminprovideinformationconcerningtheoverallhealthandnutritionalstatusof
thepatientandmayaffordprognosticinformation.
Manychemotherapyregimensmaybetoxictothekidneystherefore,acreatininelevelisnecessary
priortoinitiationofanytreatment.

LactateDehydrogenaseStudy
TheLDHleveliselevatedinmanyconditions,includingmanymalignancies.AlthoughLDHelevation
isnotspecificformelanoma,itmaybeusefulatdiagnosisandalsointhefollowupcareofpatients
withmelanoma.AmarkedlyelevatedLDHatdiagnosisoratafollowupvisitmayindicatedistant
metastases,especiallyinthelungandliver.
Althoughthespecificityandsensitivityofthistestarelow,multiplestudiesshowanelevatedLDH
leveltobeanindependentpredictivefactorforpoorprognosis.LDHlevelnowisconsideredpartof
thestagingsystemformelanoma.

ChestRadiography
ForpatientswithstageIorIIdisease,achestradiographisoftenobtained,althoughitsresultwill
likelybenegative.Todate,nostudiessupportobtainingaradiographinthesepatients,butanormal
chestradiographfindingatdiagnosisprovidesabaselineforfuturecomparison.
PatientswithstageIIIdisease,intransitdisease,orlocalrecurrenceshouldhaveachestradiograph
orCTscanofthechestbecausethelungsoftenarethefirstsiteofmetastaticdisease.

MRI
Magneticresonanceimaging(MRI)ofthebrainshouldbeobtainedduringtheworkupofapatientwith
knowndistantmetastasestodetectadditionalasymptomaticmetastaticdisease.Thisisespecially
trueforpatientsbeingconsideredforhighdoseinterleukin2treatment.
MRIofthebraininpatientswithoutknownmetastaticdiseaseshouldbereservedforthosepatients
whoaresymptomatic.

CTScanning
ChestCTscan
AchestCTscanshouldbeincludedinthestagingworkupofapatientwithstageIVdisease(ie,the
patientwithknowndistantmetastases)todetectasymptomaticmetastaticlesions.
InpatientswithstageI,II,orIIIdisease,achestCTscanshouldbeperformedonlyifclinically
indicated.

CTscanoftheabdomen
ACTscanoftheabdomenoftenisobtainedwhenevaluatingapatientwithstageIII,locallyrecurrent,
orintransitdisease.Althoughtheyieldislow,anegativeCTscanprovidesabaselinestudyforfuture
comparison.

CTscanofthepelvis
Thisstudyisindicatedonlyifapatienthaslocalregionalrecurrencebelowthewaist,issymptomatic,
orhasknownmetastaticdiseasewithahistoryofprimarytumorsbelowthewaist.

PositronEmissionTomography
PETscansarenotindicatedinearlystagedisease(StageIorII),butaPETscanmayaidinstaging
patientswithknownnodeinvolvementorintransitorsatellitelesions.ManystudiesreportthatPET
scanshavegreatersensitivitythanconventionalradiographicstudiesforthedetectionofmetastatic
disease.
OnemetaanalysisfoundPETCTscanningtobethebestimagingstudytoutilizeforfindingother
sitesofmetastasis.[15]Inparticular,fluorodeoxyglucose(FDG)PET/CTscansareavaluabletoolfor
detectingadditionalmetastasisaspartofthepreoperativeevaluationofpatientswithadvancedand
metastaticmelanoma.[16]Finally,PETscansoftenareusefulinevaluatingtheresponseofmetastatic
diseasetotherapy.

BiopsyofaSuggestiveLesion
Acompleteexcisionalbiopsyispreferred.Thesampleshouldhavea13mmmarginofhealthyskin
andshouldincludealllayersofskinandsomesubcutaneousfat.Althoughsparingofthedeepfascia
isnotstandardinbiopsiesforsuspectedmelanoma,investigatorsattheMayoClinicrecommendthis
practiceinsomepatients.[17]
Ifthesuggestivelesionislargeorsituatedinacosmeticallysensitivearea,anincisionalorpunch
biopsymaybeappropriate.Theincisionalbiopsyspecimenshouldbetakenfromthemostabnormal
areaofthelesion.
Ashavebiopsyisusuallycontraindicated,asitmaycompromisepathologicdiagnosisandcomplete
determinationofBreslowthickness.However,theNationalComprehensiveCancerNetworksuggests
thatshavebiopsyisacceptablewhentheindexofsuspicionislow,andabroadshavebiopsymay
helpoptimizediagnosticsamplingincasesoflentigomalignamelanomainsitu.[18]Incaseswherea
shavebiopsywasdoneinappropriately,acompleteexcisionalbiopsyofthelesionshouldbe
performedifpossibletodeterminethedepthandextentofthelesion.

SurgicalExcisionorReexcisionAfterBiopsy
Becausefailuretoperformareexcisionafterbiopsyofamelanomaisassociatedwithalocal
recurrencerateofashighas40%,areexcisionmustbeperformed.
Currentrecommendationsforsurgicalmarginsofexcisionareasfollows[18]:
Insitulesions0.51cmmargin
Lesions1mminthickness1cmmargin
Lesions1.012mminthickness12cmmargin
Lesions2.014mminthickness2cmmargin
Lesionsgreaterthan4mminthicknessatleast2cmmargin
AstudybyGillgrenetaldeterminedthata2cmexcisionprovidedasafeandreliantresectionmargin
totreatlesionsthickerthan2mm.[19]

ElectiveLymphNodeDissection
Patientswithclinicallyenlargedlymphnodesandnoevidenceofdistantdiseaseshouldundergoa
completeregionallymphnodedissection(LND).
Foryears,patientswithoutclinicallyenlargednodesunderwentLND.However,studiesshowthatin
patientswithmelanomasthatare14mmthick,LNDmaynotyieldasignificantsurvivaladvantage.
TheonlypatientswhoseemtobenefitfromLNDarethosewithlesions1.12mmthickandwhoare
youngerthan60years.Patientswithlesionsgreaterthan4mminthicknessarewidelyconsiderednot
tobenefitfromremovalofclinicallynegativenodes.

SentinelLymphNodeBiopsy
Lymphaticsfromanygivenregionontheskindraintoasinglelymphnode.Thisnodeiscalledthe
sentinellymphnodeandalmostalwaysisthefirstsiteofnodalinvolvementwhenmelanomaspreads
toregionalnodes.
Todeterminewhichnodeisthesentinelnode,thefollowingtwotechniques,oftenincombination,are
used.Thecombinationofthetwotechniquesallowsdetectionofthesentinelnodeinasmanyas98%
ofcases.
Thefirsttechniqueinvolvesinjectingabluedyeatthesiteoftheprimaryand,throughasmallincision
overthenodalbasin,determiningthelocationofthesentinelnode.Thenodeisthenremovedfor
pathologicevaluation.
Thesecondtechniqueinvolvesaradiolabeledsolutioninjectedintothesiteoftheprimaryandtheuse
ofahandheldgammadetectortodeterminethelocationofthesentinelnode.
Sentinellymphnodebiopsy(SLNB)isnowknowntoofferimportantprognostic,diagnostic,and
therapeuticinformation.[20]
GuidelinesfromtheNationalComprehensiveCancerNetwork(NCCN)recommenddiscussingand
offeringSLNBtopatientswithstageIBorstageIImelanomathatis0.761mmthickwithulcerationor
withamitoticrate1/mm2,or>1mmthickwithanycharacteristicadversefeatures.TheNCCN
recommendsdiscussingandconsideringSLNBtopatientswithstageIAmelanomathatis0.761mm
thick,withnoulcerationandamitoticrateof0/mm3.[18]Sentinelnodebiopsymaybeofferedeitheras
standardcareorinthecontextofaclinicaltrial.
TheNCCNdoesnotrecommendSLNBforpatientswhosemelanomais0.75mmorlessinthickness.
TheNCCNadvisesthatSLNBmaybeconsideredifconventionalriskfactorssuchasulceration,high
mitoticrate,orlymphovascularinvasionarepresent,butnotesthatthoseareveryuncommonlyfound
withmelanomasthatthin.[18]
JointguidelinesfromtheAmericanSocietyofClinicalOncology(ASCO)andSocietyofSurgical
Oncology(SSO)recommendSLNBforpatientswithintermediatethicknessmelanomas(Breslow
thickness14mm)ofanyanatomicsite.Thereislessevidenceforpatientswiththickmelanomas(T4
Breslowthickness>4mm),butsentinellymphnodebiopsyisrecommendedforstagingand
facilitatingregionaldiseasecontrol.Evidencesupportingroutinesentinellymphnodebiopsyfor
patientswiththinmelanomas(T1Breslowthickness<1mm)islacking,butitmaybeanoptionin
selectedpatientswithhighriskfeaturesinwhomthebenefitsofstagingoutweightherisksofthe
procedure.

Theguidelinesrecommendcompletionlymphnodedissection(CLND)forallpatientswithapositive
SLNBCLNDachievesgoodregionaldiseasecontrol.WhetherCLNDimprovessurvivalaftera
positivesentinellymphnodebiopsyisbeingexaminedintheongoingMulticenterSelective
LymphadenectomyTrialII.[21]
Inpatientswhosesentinellymphnodebiopsyrevealsmicrometastases,arandomizedphaseIIItrial
bySteineretalfoundnosurvivalbenefitwithCLND.Nostatisticallysignificantdifferences(ie,10%or
higher)in5yearrecurrencefreesurvival,distantmetastasesfreesurvival,ormelanomaspecific
survivalwereevidentbetween242patientswhounderwentCLNDand241patientswhoreceived
observationonly.Atamedianfollowupof35months,however,regionallymphnodemetastases
developedin14.6%ofpatientsintheobservationgroupversus8.3%ofthoseintheCLNDgroup.[22]
Cadilietalreportedthatthelikelihoodofnonsentinellymphnodemetastasiscanbepredictedonthe
basisoftotalmetastasiswithinthesentinellymphnode.Theirdatashowedthatpatientswith5mm
ofmetastasishavea30%riskofmetastasis.Incontrast,thosewithlessthan2mmoftotalsentinel
lymphnodemetastasisareunlikely(<3.67%likelihood)toharbormetastasisinnonsentinelnodes,
andthosepatientsmaynotbenefitfromadditionalnodaldissection.[23]
GotoSentinelLymphNodeBiopsyinPatientsWithMelanomaforcompleteinformationonthistopic.
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