![Page 1: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/1.jpg)
Jane L. Messina, MD September 16, 2017
Jane L., Messina, MD September 16, 2017
MELANOMAVERSUSNEVUS:STRATEGIESFORTHEDIFFICULT
DECISION
![Page 2: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/2.jpg)
Conflicts
• IserveasaconsultanttoCastleBiosciences
![Page 3: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/3.jpg)
Objec.ves
• Reviewclassicfeaturesofmelanoma• AJCCupdate• Discusscommonlyencountereddiagnos<cdilemmas
![Page 4: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/4.jpg)
Thereal thing
Asymmetry
![Page 5: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/5.jpg)
Poorcircumscrip<on
![Page 6: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/6.jpg)
Confluence,epidermaleffacement
![Page 7: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/7.jpg)
Sheet-likegrowth,atypia,mitoses
![Page 8: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/8.jpg)
AJCC8 th edi.onupdate (effec.ve
1/1/2018)
• Primarytumorstaging:– Breslowdepthtonearest0.1mm– Ulcera<on(widthmeasured!!)– Microsatellites:“microscopictumorfociwithindermisorsubQadjacenttobutdiscon<nuousfromprimary”;nominimumsizeordistance
– Repor<ngofmitoses“recommended”
![Page 9: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/9.jpg)
AJCC8 th edi.onstagingchanges
TX Primarytumorthicknesscannotbeassessed(i.e.cureIagespecimen)
T0 Regressedmelanomaormelanomaofunknownprimary
T1a
T1b
0-0.8mm
>0.8mm-1.0mmorulcera.on
T2a/b 1.1-2.0mmw/orw/oulcera.on
T3a/b 2.1-4.0mmw/orw/oulcera.on
T4a/b >4.0mmw/orw/oulcera.on
N1 N2 N3
A-occult 1 2-3 >4
B-clinical 1 2-3,atleast1clinical+ >4,atleast1clinical+
C-microsatellites 0nodes+
microsatellite
Atleast1node+
microsatellite
Atleast2nodes+
microsatellite
![Page 10: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/10.jpg)
Commonlyencounteredscenarios
• Lackofcompunc<onatthejunc<on• Specialsites• Nevoidmelanoma,dysplas<cnevus,orboth??• Downanddirtyinthedermis:spindled,pigmented,andugly
• Spitzoidlesions
![Page 11: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/11.jpg)
Lackofcompunc.onatthe
junc.on
![Page 12: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/12.jpg)
![Page 13: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/13.jpg)
Melan-A
MITF
![Page 14: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/14.jpg)
Melanoma in s i tu!
![Page 15: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/15.jpg)
Immunohistochemistry in sun-damaged
skin
• S-100– Polyclonal:crossreactswithpigmentedAK
– Monoclonal:diminished
sensi.vityinLMandALM
• HMB-45:patchy/par.alstaining
• Melan-AandMart-1:overstainingaproblem
• Sox-10orMITF:ideal
Mart-1
MITF
![Page 16: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/16.jpg)
Quan.fica.onof melanocytes insun-
damagedskin(CSD)-what is normal?
• Confluence>3melanocytesfoundin16%ofSDSspecimensonH&E,4%onMart-1
• Deepfollicularmelanocytesin6%,nestedmelanocytesin1BCCspecimen
• Melanocytedensity:LM>NMSCpa<ents
Barlow,Maize,andLang.DermatolSurg2007;33:199–207Madden,Forman,andElston.JAmAcadDermatol2011;64:548-52.)
![Page 17: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/17.jpg)
*MANOVA
200µ
• Density:numberofmelanocytes/200µm• Diameter:modeofnucleardiameterofshortestaxisof3melanocytes• Densityxdiameter>80is85%sensi<veand100%specificforMIS
AmJDermatopathol2011;33:573–578
![Page 18: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/18.jpg)
Minimaldiagnos.ccriteriaforMIS
(len.gomalignatype)
• H&EandSox-10/MITFstaining• Highnumberofmelanocytes:>10per200µm,especiallyif
presentoverabroadfront• Nuclearenlargement>9µmdiameter/pleomorphism• Inabsenceofnes<ng,confluenceof>3melanocytes• Irregulardistribu<onofmelanocytes• Descentofmelanocytesfardownadnexalstructures• Irregulardistribu<onofpigment• Melanocytespresentabovebasallayerinsignificantnumbers
AmJDermatopathology;18(6),December1996,pp560-566
![Page 19: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/19.jpg)
Residual melanomavs melanocy.c
hyperplas ia?
![Page 20: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/20.jpg)
![Page 21: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/21.jpg)
Lookatrequisi<on!“r/oresidualBCC”
Diagnosis:NoresidualBCC(melanocy<chyperplasiaatpriorbiopsysite)
![Page 22: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/22.jpg)
Previouslybiopsiedlesionwasdiscarded
MarkedcytologicatypiaMyriadresult:3.1
Diagnosis:melanomainsitu,recurrent
![Page 23: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/23.jpg)
Lesiondiameter=2mmPa<entage:8
Diagnosis:PagetoidSpitznevus
![Page 24: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/24.jpg)
PagetoidSpitz nevus
• 5-10%ofallSpitznevi• Largestseries(12):allfemale,extremitypredominant,medianage34years
• <5mmdiameter• Nests<1/3overallcellularity;singlecellsconfinedtolower½ofepidermisin75%
• Molecular/IHCanalysisnotextremelyhelpful
FernandezAP,BillingsSD,BergfeldWF,KoJS,PiliangM.PagetoidSpitznevi:clinicopathologiccharacteriza<onofaseriesof12cases.JCutanPathol2016;43:932–939
![Page 25: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/25.jpg)
Junc.onal melanocy.cneoplasmonthe
leg of a woman
![Page 26: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/26.jpg)
Diagnosis:Junc<onalmelanocy<cnevus(“len<ginous”type)
![Page 27: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/27.jpg)
“Leg-type”nevi
• Describedonthigh,belowknee,andankle• “Epithelioidcellmelanocy<cnevus”,“melanocy<cneviofanklewithatypicalfeatures”,“dysplas<cnevioflegofwomen”
• Small(4-5mm)• Singlecells=nests• Lowpagetoidspread
Dona<P,MuscardinL,CotaC,PaneraC,PaolinoG.Themelanocy<cepithelioidcellnevusofthethighofwoman:asimulatorofmelanoma.AmJDermatopathol.2012Dec;34(8):853-5.doi:10.1097/DAD.0b013e31824d4f86.PubMedPMID:22481498.CorasB,LandthalerM,StolzW,VogtT.Dysplas<cmelanocy<cneviofthelowerleg:sex-andsite-specifichistopathology.AmJDermatopathol.2010Aug;32(6):599-602.doi:10.1097/DAD.0b013e3181ce910b.PubMedPMID:20534984.KhalifehI,TaraifS,ReedJA,LazarAF,DiwanAH,PrietoVG.Asubgroupofmelanocy<cnevionthedistallowerextremity(ankle)sharesfeaturesofacralnevi,dysplas<cnevi,andmelanomainsitu:apoten<almisdiagnosisofmelanomainsitu.AmJSurgPathol.2007Jul;31(7):1130-6.PubMedPMID:17592281.
![Page 28: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/28.jpg)
©2012LippincorWilliams&Wilkins,Inc.PublishedbyLippincorWilliams&Wilkins,Inc. 2
FIGURE2
TheMelanocy.cEpithelioidCellNevusoftheThighof
Woman:ASimulatorofMelanoma.
Dona<,Pietro;Muscardin,Luca;Cota,Carlo;Panera,Chiara;Paolino,GiovanniAmericanJournalofDermatopathology.34(8):853-855,December2012.DOI:10.1097/DAD.0b013e31824d4f86
FIGURE2.Intraepidermalmelanocy<cprolifera<onwithepithelioidappearance(hematoxylinandeosinstain,originalmagnifica<onx10).
![Page 29: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/29.jpg)
EverysiteisSPECIALinitsownway
Ahn,C.,Guerra,A.,andSangueza,OP.AmJDermatopathol2016;38:867-881
![Page 30: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/30.jpg)
Acral sk in
• Len<ginous>nestedgrowth• Pagetoidspreadin36%(MANIAClesion!)• Banal,patchydermalcomponent
![Page 31: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/31.jpg)
![Page 32: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/32.jpg)
Genital ia
• Large(upto1cm)andwellcircumscribed• Highcellularityofjunc<onalnests• Bridgingandfibroplasia• Dermalmito<cac<vityin7%• LsEtAbackground:epidermaleffacementandsinglecellconfluencepossible
![Page 33: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/33.jpg)
fromSanguezaetal.
GenitalnevuswithLSetA
![Page 34: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/34.jpg)
Ear
• Poorcircumscrip<on• Irregularnes<ng,bridging,fibroplasia
• Cytologicatypialesscommon
fromSanguezaetal.
![Page 35: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/35.jpg)
Scalp
• Featuresoverlapwithdysplas<cnevi– Asymmetry,poorcircumscrip<on,irregularnes<ng,bridging,fibrosis,inflamma<on
• Mostcommonly,butnotexclusively,foundinadolescentsFisherK,MaizeJC,andMaizeJC.JAmAcadDermatol2013;68:466-72.)
![Page 36: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/36.jpg)
F lexura l s i tes
-m i l k l i ne
- an tecub i ta l /pop l i tea l fo s sae
- b reas t
• Nestsatsides/betweenrete• Dyscohesivenestsandsinglecells,len<ginousgrowth,pagetoidspread,andadnexalepithelialinvolvement
• Atypiamildtoabsent• Umbilicus:fibroplasia• Breast:atypia,highcellularitymorecommon
![Page 37: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/37.jpg)
Breast nevi
fromSanguezaetal.
![Page 38: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/38.jpg)
Nevoidmelanoma,dysplas.c
nevus,orboth?
![Page 39: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/39.jpg)
Useful immunohistochemicaltools
OR ?
• Prolifera<onmarkers:Ki-67,phosphohistoneH3
• Matura<onmarker:HMB-45• P16
![Page 40: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/40.jpg)
Ki-67:thegood,thebad,andthe
ugly
![Page 41: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/41.jpg)
Melan-A/Ki-67(MelPro) innevoid
melanoma
Nevi:<5%Melanoma:>10%
![Page 42: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/42.jpg)
MelPro in a nevus
![Page 43: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/43.jpg)
PhosphohistoneH3formitoses
• Compoundnevus:MR0.06/sqmm• Spitznevus:meanMR0.5mitoses/10HPF(range0-2)orMR0.325/sqmm
• Melanoma:meanMR24.7(range2-75)
NasrMR,El-ZammarO.AmJDermatopathol.Apr2008;30(2):117-122Phadkeetal.AmJSurgPathol2011;35:656-699Glatzetal.AmJDermatopathol2010Oct;32(7)643-649.
![Page 44: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/44.jpg)
HMB-45staininginnevusversus
nevoidmelanoma
NevusMelanoma
Pixalls• Bluenevus,DPN,trauma<zednevusexpressHMB-45
• 10%ofmelanomasshowgradientexpression
![Page 45: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/45.jpg)
p16andmal ignant poten.al
AlDhaybiRetalJAmAcadDermatol.Aug2011;65(2):357-363Ohsieetal.JCutanPathol2008;35:433-444
Retainedexpression:favorsbenign
Expressionlostin50-98%ofmelanomas
![Page 46: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/46.jpg)
p16caveats
• Manymelanomass<llexpressp16,andbenignnevimaynotexpressit
• Lossofp16stainingdoesnotequatetohomozygousdele<onof9p21– Itcanbeposi<veevenin9p21deletedlesions(15%)– Itcanbenega<veinlesionswithheterozygousloss,epigene<csilencing,orevennormal9p21
Gray-SchopferVCetal.BrJCancer2006;95:496-505Yazdanetal.AmJSurgPathol2014;38:638-645.
![Page 47: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/47.jpg)
![Page 48: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/48.jpg)
Nevoidmelanoma
• a/k/a/minimaldevia<onorsmallcellmelanoma,~3%ofmelanomas
• Non-uniformcriteria(Spitzoidlesions?)– 55%plaque-like:paralleltheques– 45%polypoid:resemblecompoundnevi– “pseudomatura<on”:cellsizeshrinks,butnucleusremainssame
– DEjunc<onmosthelpful– Deepmitoses
“Amelanocy<cneoplasmcalledanevus,butwith
subsequentdiagnos<cregret”DiwanandLazar,SurgPathClin
2009
DiwanAH,LazarAJ.SurgPatholClin2009Sep;2(3):521-33Idrissetal.JAAD2015Nov;73(5):836-42
![Page 49: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/49.jpg)
Confluenceatjunc<onParallelthequesPseudomatura<onHopefullyamitosisortwo
![Page 50: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/50.jpg)
Dermal melanomavs. pre-exis.ngnevus
![Page 51: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/51.jpg)
![Page 52: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/52.jpg)
Melanoma!
![Page 53: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/53.jpg)
Pre-exis<ngnevus!
![Page 54: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/54.jpg)
37y/omale,backlesion,“r/oatypia”
![Page 55: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/55.jpg)
![Page 56: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/56.jpg)
![Page 57: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/57.jpg)
HMB-45
![Page 58: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/58.jpg)
Sox10
![Page 59: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/59.jpg)
![Page 60: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/60.jpg)
Pagetoid melanocytes in dysplas.cnevi
• 43dysplas<cnevi• Pagetoidmelanocytesseenin63%ofcasesonIHC,11%onH&E
AmJDermatopathol2014;36:340–343)
![Page 61: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/61.jpg)
Downanddirtyinthe
dermis
![Page 62: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/62.jpg)
![Page 63: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/63.jpg)
63
S-100
P75-NGFR
Sox-10
MiTF negative (usually)
HMB-45 negative
Melan-A negative
![Page 64: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/64.jpg)
Desmoplas.cmelanoma
• Purevmixed:>or<90%paucicellulardermalgrowth– Hypercellularcomponentmaybespindleorepithelioid
64Busam et al. Am J Surg Pathol 2004; 28:1518-1525. Pure Mixed
![Page 65: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/65.jpg)
Differen.al diagnosis
• Scar:Sox-10nega<ve• DesmoplasIc(Spitz)nevus:p16NOThelpful(strongin75%pureDM)
• Neurofibroma:“fingerprint”parernCD34posi<vity• MPNST:S-100andSox-10usuallyweak/patchy,BRAFusuallynega<ve,lossofH3K27me3
65
Neurofibroma DM Desmoplastic nevus
![Page 66: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/66.jpg)
H3K27me3express ion can d is.nguish
betweenMPNSTand desmoplas.c melanoma
• LossofstainingusingC36B11an<body(CellSignalingTechnology)seenin69%ofMPNST
• However,insporadicandradia<on-relatedMPNST,absentstainingseenin95%and91%
• TMAcontaining55desmoplas<cmelanomasallshowedretainedstaining
66Prieto-Granada C et al., Am J Surg Pathol 2016; 49(4): 479-489
![Page 67: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/67.jpg)
Reta ined express ion
of H3K27me3 in
desmoplas.c/
sp ind le ce l l
melanoma
67
![Page 68: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/68.jpg)
Loss of H3K27me3 in MPNSTar is ing in
neurofibroma
68
![Page 69: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/69.jpg)
Feel ingblue
Epithelioidbluenevus
Pigmentedepithelioidmelanocytoma
Animal-typemelanoma
![Page 70: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/70.jpg)
Epithelioidbluenevus• Carneytriad
• LossofPRKAR1α
![Page 71: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/71.jpg)
Pigmentedepithelioidmelanocytoma• Epidermalhyperplasia
• Perinuclearpigmentclearing• <<5%prolifera<onrate
• 40%SLN+• Allcasesnega<vef/uthusfar
![Page 72: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/72.jpg)
Epithel ioid andfus i formbluenevus
• CSDskin,noCarneytriad,PRKAR1αretained
Yazdan,P.,Haghighat,Z.,Guitart,J.,andGermai,P.AmJSurgPathol2013;37:81–88)
![Page 73: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/73.jpg)
Clonal nevus
Clonal(“invertedtypeA”)nevus
![Page 74: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/74.jpg)
![Page 75: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/75.jpg)
MBAIT(Melanocy<cBAP-1lossassociatedintradermaltumor)
• LossofnuclearstainingbyBAP1• Screenforuveal>cutaneousmelanoma,
mesothelioma
![Page 76: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/76.jpg)
Whataboutme????
![Page 77: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/77.jpg)
Incidence(%)
BAP-1lossHRASNTRKALKROS-1BRAFRETUnknown
34%unknown
Van-Engen-vanGrunsvenetal.AmJSurgPathol2010;34:1436-41Wiesneretal.NatCommun2014;5:3116
![Page 78: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/78.jpg)
• FoundinlesionsacrossSpitzoidspectrum• Canbeiden<fiedbyimmunohistochemistry• AssociatedAST’smayhavedis<nc<vehistology• Conferpossiblesensi<vitytotargetedtherapy
• Crizo<nib,cabozantanib,vande<nibusedtotreatALKandROS-1+lungtumorsoflungandRET+thyroidtumors
Significanceofkinasefusions
![Page 79: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/79.jpg)
Moffitt 5-tiered nomenclature for melanocytic neoplasms RISKOFMALIGNANCY
1 2 3 4 5
BENIGN ATYPICAL,FAVORBENIGN
UNCERTAINMALIGNANTPOTENTIAL
ATYPICAL,FAVOR
MALIGNANT
MALIGNANT
CATEGORY
B-BLUENEVUSLIKE
C-CONGENITAL
D-DYSPLASTIC
S-SPITZOID
• CLINICALHISTORYANDAPPEARANCE• HISTOLOGICANDIMMUNOHISTOCHEMICALFINDINGS
• MOLECULARTESTINGIFNECESSARY
![Page 80: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/80.jpg)
Putting it all together
S1
BenignSpitz
nevus
S2
Atypical,
favorbenign
S3
Atypical,
uncertain
biologic
poten.al
S4
Atypical,
favor
malignant
S5
Spitzoid
melanoma
HRAS
amplifica.on
11por7pgain
6p25gain
11q13gain
9p21dele.on
orabn.CGH
6q23gain
![Page 81: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/81.jpg)
Customizing treatment
S1
BenignSpitz
nevus
S2
Atypical,
favorbenign
S3
Atypical,
uncertain
biologic
poten.al
S4
Atypical,
favor
malignant
S5
Spitzoid
melanoma
Re-
excision
0.5-1cm
Re-excision1cmwithSLNB
![Page 82: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/82.jpg)
541pa<entswithAST
SLNB303(56%)
+SLN119(39%)
CLND97(82%)
+CLND18(19%)
NoCLND22(18%)
-SLN184(61%)
NoSLNB238(44%)
5(4%)REGIONAL
RECURRENCE11(5%)REGIONAL
RECURRENCE
1DEATH 5(1%)DEATHS
Lallasetal.LancetOncol2014;15:e178–83
• 24studies,2002-2013• Averageage:24years• Medianf/u:59.3months
Let’s do the numbers….
![Page 83: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/83.jpg)
Molecular tests for accurate
iden.fica.onof melanoma
• Fluorescenceinsituhybridiza<on– Frequentlyusedintheevalua<onofdiagnos<callychallengingmelanocy<cprolifera<ons
• AtypicalSpitzoidprolifera<ons(AST),atypicalbluenevus-likeprolifera<ons
• Compara<vegenomichybridiza<on• MyriadmyPATH
![Page 84: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/84.jpg)
Oldassay6q23CEP66p25,11q13
Fluorescence in s i tu hybr idiza.on-
NeoSITE®melanoma
• NeogenomicsLaboratories(Ft.Myers,FL):$1500• Whataboutborderlinelesionssuchasthis?
Sensi<vity:87%Specificity:95%
Newassay8q249p21
94%98%
Unequivocalmelanoma
![Page 85: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/85.jpg)
FISH in histological ly ambiguousSpitzoid
les ions (AST)
Probeset ASTw/o
recurrence
“AST”withpoor
outcome
(melanoma)
TypicalSpitz
OLDsensi<vity 50-100%6,1,4
OLDspecificity 57-91%4,1 75-100%5,1
NEWsensi<vity 50-100%3,2
NEWspecificity 74-87%2,3
1DemarchisEHetal,PediatrDermatol.2014;31(5)561-92Geramietal,AmJSurgPatholFeb20133Tetzlaffetal,AmJSurgPathol.Dec20134Massietal.JAmAcadDermatol2011;64:919-355DikaetalMelResearch2015;25(4):295-3016Vergieretal.ModernPathology2011;24:613-623
![Page 86: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/86.jpg)
Spec ific F ISHabnormal i.es assoc iatedwith
outcome in border l ine les ions (AST)
• Homozygousdele.onof9p21:predictslocalrecurrenceandonlyfeaturepredic<veofdeath
• Gainof6p25and/or11q13:predictsSLNinvolvementbutnotrecurrenceordeath
• Heterozygous9p21loss:significantsen<nelnodeinvolvementbutnospreadbeyondtheregionalnodes
• 6q23(MYB)loss:associatedwithgoodlongtermoutcome
Geramietal,AmJSurgPathol,Feb2013Northetal.AmJSurgPathol2014;38:824-31Raskinetal.AmJSurgPathol2011;35:243-52
![Page 87: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/87.jpg)
Compara.vegenomic hybridiza.on
• Assesseschromosomalcopynumberchangesacross<ssue,butmissesindividualcellabnormali<es
• 95%ofmelanomasharbornumerouschromosomalgainsandlosses
• Nevirarelyshowaberra<ons• ExcepIons:
– 12-26%ofSpitznevi(esp.recurrent)have11por7qgain– SomeASThaveabnormalCGH(45%,mostcommongainof1p)
• DoesnotpredictSLNinvolvement• Prolifera<venodulesincongenitalnevimayhavewholechromosomalgains
Bas<anBCetal.JInvestDermatol.1999;113:1065–1069.Bas<anBCetal.AmJPathol.2003;163:1765–1770Raskinetal.AmJSurgPathol2011;35:243–252
![Page 88: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/88.jpg)
Compara.vegenomic hybridiza.on
• Mostcommonlyusedtodis<nguishpediatricatypicalSpitztumorfrommelanoma
• Notwidelyavailable,insurancecoveragevaries• Typicalout-of-pocketcost$2500
![Page 89: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/89.jpg)
MyriadMyPath-diagnos.caid for
equivocal les ions
• 23-geneexpressionsignaturethatcanhelpdifferen<atenevifrommelanoma-u<lizes5recutslidesfromparaffinblock
• Trainingandvalida<oncohortsof900+unequivocalmelanomaandnevi:sensi<vity90%specificity91%
• Currentlyundergoinglarge-scaletes<ngofclinicalu<litywithmelEvalPRO
Clarkeetal.JCutanPathol2015;42:244-252
Superficial
spreading>nodular>len.go
maligna
Compound
anddermal
nevi
![Page 90: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/90.jpg)
Independent val ida.onof myPath
• 1400lesionsindependentlyreviewedby3experts– Tripleconcordance:993lesions(70.9%)– Excludedindeterminatescores:860lesions(24%malignant,76%benign)
– Excludedlesionswith<10%tumorvolume:763lesions
• Sensi<vity91.5%--Specificity92.5%– Falsenega<ves-len<gomalignaanddesmoplas<cmelanomavariants
– Falseposi<ves-dysplas<cnevi
Clarkeetal.,Cancer,October2016Clarke,ASDPOctober2016
![Page 91: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/91.jpg)
29yearoldpregnantfemalewithchanginglesiononback
Junc<onaldysplas<cnevuswithmoderatetosevereatypia
![Page 92: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/92.jpg)
MyPathanddiagnos.cal ly chal lenging
les ions
• 39unequivocallesions:62%sensi<vity,95%specificity
• 78challenginglesionswithexpertconsensus(27favormalignant,30favorbenign,21ambiguous)
• myPathscoreagreedwithhistologyin64%,agreedwithFISH70%of<me– Limitedbylackofclinicaloutcome
SUMMARY:myPathscorecanincreasediagnos<ccertaintyandinfluencetreatmentrecommenda<ons,BUTperformancenotproveninambiguouslesions
Mincaetal,ModernPathology,August2016,29:832-843.
![Page 93: Jane L. Messina, MD September 16, 2017 MELANOMA VERSUS ... · Jane L. Messina, MD September 16, 2017 Jane L., Messina, MD September 16, 2017 MELANOMA VERSUS NEVUS: STRATEGIES FOR](https://reader031.vdocuments.site/reader031/viewer/2022022113/5c66863b09d3f2d0218c696a/html5/thumbnails/93.jpg)
Molecular tests for melanomadiagnosis
Summary
• FISHandmyPathsensi<vityandspecificity~90%inunequivocalmelanomasandnevi
• FISHsensi<vitydropsto50-100%andspecificityto74-87%inAST
• CGHcanaidinatypicalcaseswithnega<veFISH,buthamperedbylimitedavailabilityandreimbursement