Melanoma

Edward Buckingham, M.D. Combined Plastics Conference September 6, !!!

Melanoma " #utline

$ $ $ $ $ $ $ %eneral statistics and de&elopment 'isk factors and patient assessement Patholog( and prognosis )ork"up and staging Surgical treatment *(mph node contro&ers(+sentinel node ,d-u&ant therap(

Melanoma " Data

$ .ncidence increase fastest $ Mortalit( increase nd onl( to lung $ /th most pre&alent, incidence 01+(ear increase $ /1 skin cancer, 0/1 skin cancer death $ 2+0/ in !!!, 2+2/!! in 234/ $ !1 567, /21 facial, 61 scalp, 261 neck, 31 ear

De&elopment of 7e&i
$ Melanoc(tes
8 8 8 8 dendritic, neural crest, basal cell la(er s(nthesis of melanin 2+2! to keratinoc(tes h(perplasia" tanning+lentigines, increased ratio

$ 7e&us transformation
8 poorl( understood 8 dendritic" rounded 8 no longer lentigionous pattern" nests

De&elopment of 7e&i
$ 9unctional ne&i
8 nests along dermal"epidermal -unction

$ Compound ne&i
8 :in&ade; dermis, first as nests then cords and single cells

$ Dermal ne&i
8 -unctional component lost

E&olution of 7e&i

Melanoc(te 5(perplasia

9unctional 7e&i

Compound 7e&i

Dermal 7e&i

De&elopement of Melanoma
$ <uestionable
8 benign melanoc(tes 8 progressi&e h(perplasia+d(splasia

$ 'adial growth
8 in epidermis, lines of radii, no e=pansi&e nests or nodules 8 slow unrestricted , no metastatic potential

De&elopment of Melanoma
$ >ertical growth
8 &erticall( into dermis 8 e=pansi&e and coalescent nests and nodules 8 metastatic potential dermal l(mphatic and &ascular in&asion

$ %rowth patterns
8 biphasic" slow radial months to (ears" rapid &ertical growth 8 monophasic" rapid &ertical growth onl(

E&olution of Melanoma

D(splastic 7e&i
$ border melanoc(tic ne&i and malignant melanoma $ clinical resembles malignant melanoma $ lentiginous compound ne&us, prominent bridging across rete ridges $ aberrant in inter"rete spaces $ lamellar fibrosis of papillar( dermis, &ariable l(mphoid response

D(splastic 7e&i

D(splastic 7e&i

?(pes of Melanoma
$ $ $ $ $ ,cral lentiginous Mucosal melanoma Superfical spreading melanoma *entigo maligna melanoma 7odular melanoma

Superficial spreading
$ most common head and neck, /!1 $ @th to /th decade $ clinical mi=ture of brown+tan, pink+white irregular borders, biphasic growth $ irregular nests in epidermis $ underl(ing l(mphoid infiltrate $ enlarged nests and single cells in all epidermal la(ers

Superficial spreading

*entigo maligna
$ $ $ $ $ !1 of head and neck longest radial growth phase A2/ (rs elderl( sun e=posed areas clinical dark, irregular ink spot contiguous lintiginous proliferation, d(shesi&e, &ariable shape, atrophic epidermis, infundibular basal cell la(er of hair follicles

*entigo maligna

7odular melanoma
$ $ $ $ $ 4!1 of head and neck /th decade aggressi&e monophasic growth sun"e=posed and none=posed areas well circumscribed blue+black or nodular with in&olution in irregular plaBue $ downward tumorigenic growth, e=pand papillar( dermis into reticular dermis

7odular melanoma

Mucosal melanoma
$ $ $ $ $ $ C1 head and neck histologic staging little use local control predicts sur&i&al neck dissection for clinical 7D E'? for histo 7D ad-u&ant interferon alpha "b

'isk factors
$ $ $ $ $ $ ?(pe . or .. skin at(pical and congenital ne&i actinic skin changes histor( of melanoma famil( histor( of melanoma, at(pical ne&i histor( of significant sun e=posure FblisteringG

Clinical
$ earl(, increase in siHe, change in shape or color of pigmented lesion $ most common s(mptom pruritis $ late, tenderness, bleeding, ulceration $ ,BCDEIs Fas(mmetr(, border, color, diameter, ele&ation, surrounding tissueG $ Epiluminescence microscop( FE*MG

Biops(
$ $ $ $ e=cisional biops( or sauceriHation if small incisional if large Depth of biopsy must be to sub-Q fat if melanoma a second e=cision must be performed

Patholog(
$ diagnosis, tumor thickness in millimeters, margins $ histologic subt(pe, anatomic site, Clark le&el, mitotic rate, growth phase, ulceration, regression, l(mphoc(tes, angiol(mphatic spread, neurotropism, microsatellitosis, precursor lesion

Prognosis
$ Breslow Fthickness in millimetersG strongest predictor

Prognosis
$ Clark le&el less predicti&e, thin skin useful

Prognosis
$ anatomic site, ulceration, gender, histologic t(pe, nodal disease $ head and neck" scalp worse $ e=tremit( better trunk $ women better men $ l(mph node D
8 Breslow thickness, ulceration, J pos. nodes 8 Cohen 2! (r sur&i&al J nodes positi&e

)ork"up
$ 56P
8 entire skin, inguinal, a=illar(, supracla&icular, 567 nodes,especiall( primar( drainage 8 brain, bone, %., constitutional s(mptoms 8 palpable nodes K7,

$ *abs and imaging

8 &ar(, CE' to routine C? chest and *K? 8 567 C? neck routine 8 .f stage ...FregionalG or .> FdistantG " C? head, chest, abdomen, pel&is

)ork"up
$ KD%"PE?
8 some use in distant disease 8 sensiti&it( 201 in stud( with S*7 biops(

Staging"Clark
$ *e&el . " in situ at basement membrane $ *e&el .. " through basement membrane into papillar( dermis $ *e&el ... " spread to papillar(+reticular interface $ *e&el .> " spread to reticular dermis $ *e&el > " sub"< in&asion

Staging"Breslow
$ $ $ $ L!.06 mm " thin !.06 " 2.@3 " intermediate 2./! " @.!! " intermediate A@.!! mm " thick

Staging
$ CS+PS F., .., ...G $ ,9CC" Stage . and .. " local, ... " regional .> " distant

,9CC Staging

Surgical ?reatment
$ 'ecommended margins &ar( $ 'ule of thumb
8 L2mm then 2 cm 8 2"@mm then cm 8 A@mm then 4 cm

$ ,ll depths to underl(ing muscle fascia

7odal Disease
$ CS".. remo&e regional l(mphatics depending on location of primar( and presence of distant metastasis

CS." ?he Debate

$ Balch stud(" nonrandomiHed
8 / and 2! (r sur&i&al intermediate thickness F!.06"4.33G doubled with E*7D 8 / and 2! (r sur&i&al for thin FL!.06G and thick FA@.!G no change with E*7D

Balch Stud(

CS. " ?he Debate

$ Kour prospecti&e randomiHed trials
8 Ma(o clinic 4 groups stage . FE*7D, dela(ed, noneG no sur&i&al difference, increased complications if none, criticiHed not looking at subgroups to benefit 8 )5# no sur&i&al benefit, criticiHed no subgroups, largel( e=tremit( lesions in females

CS. " ?he Debate

$ Kour prospecti&e randomiHed trials
8 Balch " no o&erall / (r difference, impro&ed in patients , 6! (rs with E*7D, 2" mm tumors, no ulceration, or both benefited, 8 )5# trunk 2./ mm or more immediate or dela(ed no significant sur&i&al benefit, howe&er was between E*7D with occult metastasis and later de&elopers with dela(ed *7D

?he Debate " P'# E*7D

$ seBuential dissemination theor( $ 4!1 stage . 6 .. occult disease $ #nce palpable 0!"C!1 distant disease, 2! (r sur&i&al 2/" /1, / (r 2" nodes micrometastasis 6/1 $ BalchIs non"randomiHed stud(

?he Debate " C#7 E*7D

$ randomiHed trials $ 0!1 no occult disease $ seBuential dissemination onl( theor(

BalchIs recommendations
$ ?hree groups
8 local, local plus micro, local plus distant

$ ?hin " 3/1 cure rate no benefit to E*7D $ .ntermediate " 6!1 regional, !1 distant, benefit E*7D $ ?hick " A6!1 regional, A0!1 distant, no benefit $ Should consider other factors as well

Sentinel 7ode ?heor(

$ Essence of debate to identif( those with occult metastasis $ Morton" first node in group to recei&e flow from tumor site

S*7 " procedure

$ isosulfan blue in-ection at tumor site, follow channels to node
8 studies with E*7D C!1 sensiti&it(, specificit( 331

$ preoperati&e l(mphscintigraph(, intra" operati&e radiol(mphoscintigrap(, and isosulfan blue d(e

8 63./1 S*7 e=cised blue d(e, C4./1 :hot;, combined success 361, location matters

S*7 " Mtilit(

$ prognostic indicator " stud( S*7 status most significant indicator of disease"free and disease"specific sur&i&al $ patholog(
8 56E, S"2!!, 5MB"@/ limited b( J sections 8 re&erse transcription with pol(merase chain reaction F'?"PC'G" peripheral blood and nodes, Fm'7, t(rosinaseG 3 E*7D 4C1 path positi&e, 661 '?"PC' positi&e

,d-u&ant ?herap(
$ 'adiation
8 high dose F@!!"/!! c%(G bulk(, residual, recurrent, unresectable, ill 8 lentigo maligna / (r cure C!1 Fdisfiguring, debilitating locationG 8 ad-u&ant" trend toward impro&ed regional control in 7D dissected necks 8 palliate " especiall( bon( mets

,d-u&ant ?herap(
$ Chemotherap(
8 response /1, durable control 21 8 consider in CS. with A2./ mm, CS.. with )*E, ?7D 8 no sur&i&al ad&antage demonstrated 8 single agent dacarbaHine FD?.CG 8 multiple combinations carmustine, cisplatin, D?.C, tamo=ifen

,d-u&ant ?herap(
$ .mmunotherap(
8 unusual beha&ior, no sur&i&al benefit

$ .nterferon
8 EC#% 26C@, A@mm or 7D, 6.3 (rs high dose .K7"alpha" b, impro&ed disease"free and o&erall sur&i&al appro=. 2 (r. 61 dropout rate to=icit(

Summar(
$ .ncidence and deaths on rise $ Sur&i&al rates increasing due to detection and thorough treatment $ Depth and nodal status most important prognostic indicators $ E*7D still debated $ S*D useful $ #ther modalities therap( further research