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MalignantMelanomaGuidelines
GUIDELINES

GuidelinesSummary
Guidelinescontributors:WesleyWu,MD,ResidentPhysician,DepartmentofDermatology,Baylor
CollegeofMedicineMohsinRMir,MD,Director,HighRiskSkinCancerClinic,AssistantProfessor,
MohsSurgery,LaserandCosmeticSurgery,DepartmentofDermatology,BaylorCollegeofMedicine

Screening
In2016,theU.S.PreventiveServicesTaskForce(USPSTF)concludedthereisnotenoughevidence
torecommendfororagainstroutinescreening(totalbodyexaminationbyaprimarycarephysicianor
patientselfexamination)forearlydetectionofskincancersintheadultgeneralpopulation.[74]
TheUSPSTFdidnotethefollowingclinicalconsiderations:
Skincancerofanytypeoccursmorecommonlyinmenthaninwomenandamongpersonswith
afaircomplexion,personswhouseindoortanningbeds,andpersonswithahistoryofsunburns
orpreviousskincancer.
Specificriskfactorsformelanomaincludehavinganatypicalmole,multiple(ie,100)moles,
andhavingafamilyhistoryofmelanoma.
Theriskofmelanomaincreaseswithagethemedianageatdiagnosisis63years,andthe
medianageatdeathis69years.
Clinicalvisualskinexaminationshouldassessskinlesionsforasymmetry,borderirregularity,
colorvariability,diametergreaterthan6mmorevolutionovertime(ABCDEcriteria)

ClinicalPresentationandWorkup
TheNationalComprehensiveCancerNetwork(NCCN)supportstheconceptthatmostmelanoma
recurrencesarediagnosedclinically.CurrentNCCNguidelinesstatethatnofurtherworkup(ie,
baselinelaboratorytestsandimagingstudies)isrequiredinstage0(melanomainsitu)andfor
asymptomaticpatientswithstageIA,IB,orIIAmelanoma.(PhysicianQualityReportingSystem
(PQRS)measure#224concernsoverutilizationofimagingstudiesinmelanoma.)Imaging(CT
scanning,PET,MRI)shouldbeobtainedonlyasclinicallyindicatedtoevaluatespecificsignsor
symptomsinstageIIBandIICpatientswithhigherriskmelanoma.[18]
The2015guidelinesfromtheEuropeanSocietyofMedicalOncology(ESMO)requirediagnosis
basedonafullthicknessexcisionalbiopsywithaminimalsidemarginthathasbeenprocessedbyan
experiencedpathologyinstitute.Histologyreportsshouldincludethefollowing[75]:
Informationonthetypeofmelanoma
Actinicdamage
Maximumverticalthicknessinmillimetres
InformationonmitoticrateincaseofpT1

Presenceofulceration
Presenceandextentofregression
Clearanceofthesurgicalmargins
Physicalexaminationwithspecialattentiontoothersuspiciouspigmentedlesions,tumoursatellites,
intransitmetastases,regionalLNanddistantmetastasesisrequried.Imagingisnotneededforlow
riskmelanomasbutisrequiredinhighertumorstagesforaccuratestaging.[75]
GuidelinesestablishedbytheAmericanAcademyofDermatology(AAD)in2011areasfollows[76]:
Baselinetestsarenotrecommendedinasymptomaticpatientswithanystageofprimary
melanoma(IAIIC)
Regularclinicalfollowupandintervalpatientselfexaminationofskinandregionallymphnodes
arethemostimportantmeansofdetectingrecurrentdiseaseornewprimarymelanoma
Findingsfromhistoryandphysicalexaminationshoulddirectneedforfurtherstudiestodetect
local,regional,anddistantmetastasis
Surveillancelaboratorytestsandimagingstudiesinasymptomaticpatientswithmelanomahave
lowyieldfordetectionofmetastaticdiseaseandareassociatedwithrelativelyhighfalsepositive
rates
CurrentNCCNguidelinesdonotrecommendsurveillance(followup)laboratoryorimagingstudiesfor
asymptomaticpatientswithstageIA,IB,andIIAmelanoma(ie,tumors4mmdepth).Imagingstudies
(chestradiograph,CTand/orPETCT)shouldbeobtainedasclinicallyindicatedforconfirmationof
suspectedmetastasisortodelineatetheextentofdisease.[18]
TheNCCNadvisesthatimagingstudiesmaybeconsideredtoscreenforrecurrent/metastaticdisease
inpatientswithstageIIBIVdisease,althoughthisrecommendationremainscontroversial.Routine
laboratoryorradiologicimaginginasymptomaticmelanomapatientsofanystageisnot
recommendedafter5yearsoffollowup.[18]
Whileabnormallaboratorytestresultsarerarelythesoleindicatorofmetastaticdisease,serum
lactatedehydrogenase(LDH)levelswereincorporatedintotheAmericanJointCommitteeonCancer
(AJCC)2002melanomastagingguidelinesfortheclassificationofstageIV(distant)disease.
ElevatedLDHlevelsareassociatedwithworsesurvivalinthissubgroupandremainapowerful
predictorofsurvivalinthe2009AmericanJointCommissionforCancer(AJCC)CancerStaging
Manual(7thEd)formelanomaoftheskin.[77]

SentinelLymphNodeDissection
ThemelanomaguidelinesfromtheNationalComprehensiveCancerNetwork(NCCN)donot
recommendsentinellymphnodebiopsyforpatientswithinsitumelanoma(stage0).[18]
Evidencesupportingroutinesentinellymphnodebiopsyforpatientswiththinmelanomas(T1
Breslowthickness<1mm)islackingandrecommendationsremaincontroversial.TheNCCNdoes
notrecommendsentinellymphnodebiopsyforpatientswithlesions0.75mmorthinner.{ref2}ESMO
recommendssentinellymphnodebiopsywithlesions>1mmand/orulcerationforprecisestaging.In
addition,sentinellymphnodebiopsyshouldbediscussedwithpatientswithaT1btumorgreaterthan
0.75mm.[75]
TheAmericanAcademyofDermatology(AAD)recommendsconsiderationofsentinellymphnode
biopsyinpatientswithlesions,includingthoselessthan0.76mm,withanyofthefollowinghighrisk
features[76]:

Ulceration
Mitosis
Angiolymphaticinvasion
Positivedeepmargin
Youngpatientage
However,recentdatasuggestthatthepresenceofasinglemitoticfiguremaynotcorrelatewellwith
sentinelnodestatusinthinlesions.[78]Inaddition,thepresenceofregressioninthinlesionsis
associatedwithalowerriskofnodalmetastasis.[79]
The2012jointguidelinesfromtheAmericanSocietyofClinicalOncology(ASCO)andSocietyof
SurgicalOncology(SSO),aswellasthe2009AmericanJointCommissionforCancer(AJCC)
MelanomaStagingandClassificationCommittee(BALCH),recommendsentinellymphnodebiopsy
forpatientswithintermediatethicknessmelanomas(Breslowthickness14mm)atanyanatomicsite.
Thereislessevidenceforpatientswiththickmelanomas(T4Breslowthickness>4mm),butsentinel
lymphnodebiopsyisrecommendedforstagingandfacilitatingregionaldiseasecontrol.
Theguidelinesalsorecommendcompletionlymphnodedissection(CLND)forallpatientswitha
positivesentinellymphnodebiopsy.CLNDachievesgoodregionaldiseasecontrolhowever,its
impactondiseasefreesurvivalremainstobeclarifiedintheongoingMulticenterSelective
LymphadenectomyTrialII.[21]

MohsSurgery
TheNCCNcitesanMMSstudythatemployedMMSenhancedbyimmunohistochemicalstainingas
theprimarytreatmentmodalityformelanomainsitu,whichresultedin99%removalofmelanomain
situwhenatotalsurgicalmarginof9mmwasused,versusan86%rateofremovalwith6mm
margins.ThestaincomprisedantibodiestoamelanomaantigenrecognizedbyTcells(MART1).[18,
80]

TheappropriateusecriteriaforMMSfromtheAAD,AmericanCollegeofMohsSurgery(ACMS),
AmericanSocietyforDermatologicSurgeryAssociation(ASDSA),andtheAmericanSocietyforMohs
Surgery(ASMS)furtherstatethatMMSisappropriateforallrecurrentmelanomainsituandlentigo
maligna,aswellasprimarylesionsatthefollowingsites[81]:
Head
Neck
Hands
Feet
Pretibialsurface
Nails
Ankles

WideExcisionSurgicalMargins
Forwideexcisionofprimarymelanoma,theNCCN,AADandESMOpracticeguidelinesagreeonthe
followingsurgicalmarginrecommendationsforprimarymelanoma[18,76,75]:
TumorinsituMarginsize0.51.0cm
Tumorsmallerthan1mmMarginsize1cm

Tumor12mmMarginsize12cm
Tumor24mmMarginsize2cm
Tumorgreaterthan4mmMarginsizeatleast2cm

RadiationTherapy
NCCNguidelinesrecommendconsiderationofradiationtherapyinthefollowingsituations[18]:
Primarydisease:Asadjuvanttreatmentinselectedpatientswithfactorsthatincludedeep
desmoplasticmelanomawithnarrowmargins,extensiveneurotropism,orlocallyrecurrent
disease
Regionaldisease:Asadjuvanttreatmentfollowingresectionofcategory2BnodesandLDH<
1.5timestheupperlimitofnormal,andextranodaltumorextensionaspalliativetreatmentfor
unresectabledisease
Metastaticdisease:Aseitheradjuvantorprimarytreatmentforbrainmetastases
ESMOrecommendsconsideringstereotacticradiationofregionalorsingledistantmetastaticdisease.
[75]

TreatmentforAdvancedMelanoma
NCCNrecommendationsfortreatmentofmelanomastageIVdiseasewithdistantmetastasisinclude
thefollowing[18]:
Treatmentdependsonwhethermelanomaislimited(resectable)ordisseminated(unresectable)
Inlimiteddisease,resectionisrecommendedalternatively,observationorsystemictherapymay
bechosen
Treatmentforlimiteddiseaseincludesclinicaltrialenrollmentorsystemictherapy
Forpatientswithunresectablediseasewithoutbrainmetastases,treatmentincludessystemic
therapypatientswithbrainmetastasesrequiretreatmentofthecentralnervousdisease
Preferredregimensforsystemictherapy,accordingtotheNCCNguidelines,areasfollows[18]:
Ipilimumab
Dabrafenibplustrametinib
Pembrolizumab
Nivolumab
Otheractiveregimensincludethefollowing,amongothers[18]:
Vemurafenib
Dabrafenib
Trametinib
Highdoseinterleukin2(IL2)
Dacarbazine,temozolomide,orpaclitaxelbasedchemotherapy

FollowupforMelanomaCancerSurvivors
FollowupguidelinesfromtheNationalComprehensiveCancerNetworkarelistedbelow.[18]
Followupforstage0insituisasfollows:

Atleastannualskinexaminationforlife
Educatepatientinmonthlyselfexaminationofskin
FollowupforstageIAisasfollows:
Historyandphysicalexamination(H&P),withemphasisonlymphnodesandskin,every312
mofor5y,thenannuallyasclinicallyindicated
Atleastannualskinexaminationforlife
Educatepatientinmonthlyselfexaminationofskinandlymphnodes
FollowupforstageIBIV(patientswithnoevidenceofdisease)isasfollows:
H&P(withemphasisonnodesandskin)every36mofor2y,thenevery312mofor2y,then
annuallyasclinicallyindicated
Chestradiography,lactatedehydrogenase(LDH)level,andcompletebloodcellcount(CBC)
every612mo(optional)
RoutineimagingisnotrecommendedforstageIBorIIAdisease
Computedtomography(CT)scanstofollowupforspecificsignsandsymptoms
ConsiderCTand/orPETscanstoscreenstageIIBandhigherforrecurrent/metastaticdisease
every3to12months
Atleastannualskinexaminationforlife
Educatepatientinmonthlyselfexaminationofskinandlymphnodes
Medication
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