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Diagnosis of Diagnosis of Cutaneous MelanomaCutaneous Melanoma
R. Stan Taylor, M.D.R. Stan Taylor, M.D.JB Howell ProfessorJB Howell Professor
In Melanoma Education and DetectionIn Melanoma Education and Detection
Department of DermatologyDepartment of DermatologyUniversity of Texas SouthwesternUniversity of Texas Southwestern
Prepared for Melanoma Symposium, Dallas, TX 11/05/2005 Prepared for Melanoma Symposium, Dallas, TX 11/05/2005
►► A malignancy arising from pigment A malignancy arising from pigment producing cells.producing cells.
MelanomaMelanomaMelanomaO
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DEFINITIONDEFINITION
►► Internal: retina and intestinesInternal: retina and intestines
CutaneousCutaneous
►► The tumor resulting from The tumor resulting from malignant growth of the cells malignant growth of the cells invades locally and has a invades locally and has a relatively high risk of metastases relatively high risk of metastases beyond the skin. beyond the skin.
►► Skin: Skin: melanocytesmelanocytes and nevus cellsand nevus cells
►► increased CM with:increased CM with:decreased latitude of decreased latitude of residenceresidencelocation in sunlocation in sun--exposed anatomic exposed anatomic sitessitesmigration from migration from countries of low to countries of low to high sun exposure, high sun exposure,
Ultraviolet RadiationUltraviolet RadiationUltraviolet Radiation
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wETIOLOGYETIOLOGY
MelanomaMelanomaMelanomaCutaneousCutaneous
►► Intermittent intense Intermittent intense exposure, particularly exposure, particularly early in life, also early in life, also places individuals at places individuals at risk for melanoma.risk for melanoma.
Genetic FactorsGenetic FactorsSKIN TYPESKIN TYPEGenetic DeterminationsGenetic DeterminationsSkin TypeSkin TypeSkin Type
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Fair skin is at increaseCM risk
• Type I & II higher CM risk
Type II
Type I
Type III Type IV Type V
• CM linked to sunburn, due to skin typ
MelanomaMelanomaMelanomaCutaneousCutaneous
Genetic FactorsGenetic FactorsSKIN TYPESKIN TYPEGenetic DeterminationsGenetic DeterminationsGenetic Determinations
• 22% CM associated w/ DN
• Min. risk any DN becoming CM
• DN in CM prone families (32,000/US)
• DN in isolated individual (millions)
DN indicator of CM riskOve
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wETIOLOGYETIOLOGYETIOLOGY
MelanomaMelanomaMelanomaCutaneousCutaneous
Dysplastic NeviDysplasticDysplastic NeviNevi
►► Genetic Genetic defects have defects have localized to localized to chromosomes chromosomes 1, 6, 7, 9 and 1, 6, 7, 9 and 1010Genetic DefectsGenetic DefectsGenetic Defects
►► Inheritance Inheritance is is autosomalautosomaldominant; dominant; multiple multiple genes genes contributecontribute
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►► 88--12% MM pt have 1 12% MM pt have 1 relative w/ relative w/ hxhx CMCM
►► 1% w/ living relative w/ CM 1% w/ living relative w/ CM
MelanomaMelanomaMelanomaCutaneousCutaneous
Normal MelanocytesNormal Normal MelanocytesMelanocytes
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wPATHOPHYSIOLOGYPATHOPHYSIOLOGY
MelanomaMelanomaMelanomaCutaneousCutaneous
•• Loss of growth control Loss of growth control allows cells to grow allows cells to grow uncontrollably. uncontrollably. •• Occurs locally, in a Occurs locally, in a horizontalhorizontal fashion.fashion.•• Malignant Malignant melanocytesmelanocytesassume a assume a verticalvertical growth growth pattern invading across pattern invading across the dermalthe dermal--epidermal epidermal junction.junction.•• If the malignant cells If the malignant cells enter the dermis they enter the dermis they can then leave the skin can then leave the skin via blood vessels and via blood vessels and lymphaticslymphatics..Malignant MelanocytesMalignant Malignant MelanocytesMelanocytes
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MelanomaMelanomaMelanomaCutaneousCutaneous
• Lymphatic metastases commonly lead to regional lymph node enlargement but occasionally regional nodes may be skipped and metastases appear in distant nodal areas.
• Hematogenousmetastases allow cells to spread rapidly throughout the body. Studies have shown that less than 1% of cells remain viable in the blood stream and therefore hematogenous spread is likely to be more clinically important in patients with large tumor burdens
MetastasisMetastasisMetastasis
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MelanomaMelanomaMelanomaCutaneousCutaneous
•• The degree of vertical growth or thickness of the tumor The degree of vertical growth or thickness of the tumor in the skin is consistently the most reliable predictor.in the skin is consistently the most reliable predictor.•• Thickness and bad prognosis are directly relatedThickness and bad prognosis are directly related
>
PrognosisPrognosisPrognosis
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MelanomaMelanomaMelanomaCutaneousCutaneous
•• Since 1980 the Since 1980 the number of melanomas number of melanomas diagnosed annually in diagnosed annually in the USA has doubled. the USA has doubled.
•• During the same period During the same period the population has the population has increased by only 11%.increased by only 11%.
•• Lifetime risk for melanoma in 1980 was Lifetime risk for melanoma in 1980 was 1 in 250 and now it is 1 in 75.1 in 250 and now it is 1 in 75.
INCIDENCEINCIDENCEO
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MelanomaMelanomaMelanomaCutaneousCutaneous
19351960
19801985 1990 2000
1:15001:15001:6001:600
1:2501:250
1:1501:1501:1201:120
1:901:90
SKIN CANCER DEATHSIN THE US
SCCSCC
MelanomaMelanoma
•• Approximately Approximately 72007200 deaths are deaths are attributable to attributable to melanoma each melanoma each year.year.
•• The mortality rate The mortality rate for melanoma has for melanoma has also increased but also increased but not as dramatically.not as dramatically.
MortalityMortalityMortality
INCIDENCEINCIDENCEO
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MelanomaMelanomaMelanomaCutaneousCutaneous
75% due to melanoma
Risk FactorsRisk FactorsRisk Factors
INCIDENCEINCIDENCEO
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MelanomaMelanomaMelanomaCutaneousCutaneous
•• blistering sun burns, blistering sun burns, particularly multiple and particularly multiple and earlier in lifeearlier in life
•• family/personal history family/personal history of of dysplasticdysplastic nevi or nevi or melanomamelanoma
•• sun exposuresun exposure
•• fair complexion fair complexion (skin types I and II)(skin types I and II)
Type IIType I
Type III Type IV Type V
•• Any pigmented lesion Any pigmented lesion that has changed in size, that has changed in size, color or shapecolor or shape•• or become an irritation to or become an irritation to the patient for any reasonthe patient for any reason•• should be evaluated for should be evaluated for the possibility of the possibility of malignancy malignancy
Unaided EvaluationUnaided EvaluationUnaided Evaluation
CLINICAL EVALUATIONCLINICAL EVALUATIONA
sses
smen
tA
sses
smen
tA
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smen
tMelanomaMelanomaMelanomaCutaneousCutaneous
ASYMMETRYASYMMETRY•• nonidenticalnonidentical halveshalvesdivided by a linedivided by a linedrawn through lesiondrawn through lesion
BORDERBORDER•• scallopedscalloped•• coast of Mainecoast of Maine
COLORCOLOR•• nonhomogeneousnonhomogeneous•• varingvaring shades ofshades ofbrown, black,brown, black,red, white, bluered, white, blue
DIAMETERDIAMETER•• > 6 mm> 6 mm•• > pencil eraser> pencil eraser
Abnormal Patternsof Pigmentation
Abnormal PatternsAbnormal Patternsof Pigmentationof Pigmentation
CLINICAL EVALUATIONCLINICAL EVALUATIONA
sses
smen
tA
sses
smen
tA
sses
smen
tMelanomaMelanomaMelanomaCutaneousCutaneous
Exam AidsExam AidsExam Aids
CLINICAL EVALUATIONCLINICAL EVALUATIONA
sses
smen
tA
sses
smen
tA
sses
smen
tMelanomaMelanomaMelanomaCutaneousCutaneous
Serial photographsSerial photographs: Total skin surface; one copy for home & : Total skin surface; one copy for home & one for clinic; used as a reference.one for clinic; used as a reference.
White lightWhite light::scattered at surfacescattered at surfaceWoodWood’’s lamps lamp::accentuates slightaccentuates slightdifferences in colordifferences in color
Mole mapping devices:Mole mapping devices: computer programs allow the clinician computer programs allow the clinician to store digital images in a computer data base for easy to store digital images in a computer data base for easy comparative reference.comparative reference.
Exam AidsExam AidsExam Aids
SURFACE ILLUMINATIONSURFACE ILLUMINATIONA
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tMelanomaMelanomaMelanomaCutaneousCutaneous
OilOil •• Visualization into pigmented Visualization into pigmented lesions by passage of intense lesions by passage of intense white light through a thin layer white light through a thin layer of mineral oil and a glass.of mineral oil and a glass.
•• DermatoscopeDermatoscope: 10x lens; halogen : 10x lens; halogen bulb; battery power.bulb; battery power.
•• Mole Max machineMole Max machine -- digital camera digital camera that captures that captures epiluminescentepiluminescent images; images; stores images; compares images to a stores images; compares images to a library of pigmented lesions to assist library of pigmented lesions to assist in decisions.in decisions.
•• Malignant growth patterns have a Malignant growth patterns have a characteristic pigmentation pattern.characteristic pigmentation pattern.
Exam AidsExam AidsExam Aids
EPILUMINESCENCEEPILUMINESCENCEA
sses
smen
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smen
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tMelanomaMelanomaCutaneousCutaneousGlassGlass
Clinical viewClinical view
EpiluminescentEpiluminescent viewview
Level II MelanomaLevel II Melanoma
Clinical viewClinical view
EpiluminescentEpiluminescent viewview
LentigoLentigo
MoleMaxMoleMax IIII
VideomicroscopeVideomicroscopeMacro cameraMacro camera
DERMA Instruments, www.derma.comDERMA Instruments, www.derma.com
•• NevoscopeNevoscope: : camera lens; camera lens; by by TransliteTranslite, , www.tlite.comwww.tlite.com
•• ““back lightingback lighting”” of lesion by of lesion by angling the light to enter skin at the angling the light to enter skin at the periphery of the lesion; light periphery of the lesion; light penetrates underneath the lesion penetrates underneath the lesion reflecting back through lesions.reflecting back through lesions.
•• Characteristic Characteristic pigmentarypigmentarypatterns are seen for both patterns are seen for both benign and malignant benign and malignant lesions.lesions.
Exam AidsExam AidsExam Aids
TRANSILLUMINATIONTRANSILLUMINATIONA
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tMelanomaMelanomaMelanomaCutaneousCutaneous
SHAVESHAVE
PUNCHPUNCHEXCISIONEXCISION
SAUCERIZATIONSAUCERIZATION
GOALGOAL::•• diagnosisdiagnosis•• depthdepth
BIOPSYBIOPSYA
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smen
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tMelanomaMelanomaMelanomaCutaneousCutaneous
Ass
essm
ent
Ass
essm
ent
Ass
essm
ent ►► Morphology: depends upon the point in their Morphology: depends upon the point in their
malignant evolutionary process. malignant evolutionary process.
EM
DiagnosisDiagnosisDiagnosis
PATHOLOGICAL EVALUATIONPATHOLOGICAL EVALUATION
PagetoidPagetoid spreadspread-- cells in base of cells in base of epidermis.epidermis.In situIn situ-- cells confined to epidermis.cells confined to epidermis.Horizontal or Radial Growth PhaseHorizontal or Radial Growth Phase--cells spread through the epidermis.cells spread through the epidermis.Vertical Growth PhaseVertical Growth Phase-- cells penetrate cells penetrate into the dermis.into the dermis.Round or oval cells vs. spindle shapes.Round or oval cells vs. spindle shapes.
►► Special stains; used to differentiate tumor Special stains; used to differentiate tumor types.types.
Silver stains (Fontana Silver stains (Fontana -- Masson stain) for Masson stain) for the detection of melanin.the detection of melanin.ImmunohistochemicalImmunohistochemical (antibodies such (antibodies such as S as S -- 100, HMB 100, HMB -- 45, MART1, and 45, MART1, and VimentinVimentin))Electron microscopy (detect Electron microscopy (detect melanosomesmelanosomes))
MelanomaMelanomaMelanomaCutaneousCutaneous
►► Prognosis and therapeutic Prognosis and therapeutic considerations are based on considerations are based on the depth of penetration of the depth of penetration of malignant cellsmalignant cells
BreslowBreslow depth: depth: thickness thickness measured in millimeters.measured in millimeters.
Clark's Levels:Clark's Levels: depth depth classified by cell penetration classified by cell penetration into different compartments into different compartments of the skin.of the skin.►► Clark Level IClark Level I-- cells confined cells confined
to the epidermisto the epidermis►► Clark's Levels VClark's Levels V-- deep deep
penetration into penetration into subcutaneous fatsubcutaneous fat
PrognosisPrognosisPrognosis
PATHOLOGICAL EVALUATIONPATHOLOGICAL EVALUATIONA
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►► HyperpigmentedHyperpigmented lesionslesions►► Commonly progress from flat Commonly progress from flat
(childhood) to (childhood) to pedunculatedpedunculated(adulthood)(adulthood)
►► Include the following:Include the following:JunctionalJunctional nevinevi: macular to : macular to slightly elevated; uniform slightly elevated; uniform brown to black; measure 0.1 to brown to black; measure 0.1 to 0.6 cm; often confused w/ CM; 0.6 cm; often confused w/ CM; rarely go to CM.rarely go to CM.Compound nevi:Compound nevi: slightly slightly elevated, dome shaped, smooth elevated, dome shaped, smooth or or verrucoidverrucoid papules; low risk papules; low risk of CM.of CM.IntradermalIntradermal nevi: nevi: dome dome shaped, smooth shaped, smooth verrucoidverrucoidpedunculatedpedunculated nodules; tend to be nodules; tend to be benign.benign.
Acquired Melanocytic NeviAcquired Acquired MelanocyticMelanocytic NeviNevi
PRECURSOR LESIONSPRECURSOR LESIONSC
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ntat
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Clin
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Pre
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atio
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linic
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ntat
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MelanomaMelanomaMelanomaCutaneousCutaneous
►► Detected at or shortly Detected at or shortly after birth.after birth.
►► Macular or plaqueMacular or plaque►► Vary greatly in size Vary greatly in size
( mm to many cm).( mm to many cm).►► May be mixed with May be mixed with
other components of other components of the skin including hair.the skin including hair.
►► Risk of CM increases Risk of CM increases w/ size.w/ size.
Congenital Melanocytic NeviCongenital Congenital MelanocyticMelanocytic NeviNevi
PRECURSOR LESIONSPRECURSOR LESIONSC
linic
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rese
ntat
ion
Clin
ical
Pre
sent
atio
nC
linic
al P
rese
ntat
ion
MelanomaMelanomaMelanomaCutaneousCutaneous
►► MelanocyticMelanocytic nevi which nevi which develop a hypo or develop a hypo or depigmenteddepigmented ring around ring around them.them.
►► Associated with Associated with vitiligovitiligo..►► Commonly seen in Commonly seen in
teenagers.teenagers.►► Thought to be an Thought to be an
immune response; often immune response; often halo nevi will regress halo nevi will regress leaving normal skin.leaving normal skin.
►► Asymmetry suggests CMAsymmetry suggests CM
Halo NeviHalo NeviHalo Nevi
PRECURSOR LESIONSPRECURSOR LESIONSC
linic
al P
rese
ntat
ion
Clin
ical
Pre
sent
atio
nC
linic
al P
rese
ntat
ion
MelanomaMelanomaMelanomaCutaneousCutaneous
Clin
ical
Pre
sent
atio
nC
linic
al P
rese
ntat
ion
Clin
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Pre
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atio
n►► Differ from common Differ from common
melanocyticmelanocytic nevi:nevi:►► marked size variability.marked size variability.►► irregular shape.irregular shape.►► larger in size (5 larger in size (5 -- 12 mm).12 mm).►► angulated or indistinct angulated or indistinct
borders.borders.►► non sunnon sun--exposed areas.exposed areas.►► large numbers (75 large numbers (75 -- greater greater
than 100).than 100).►► continue to develop over the continue to develop over the
patient's lifetime.patient's lifetime.►► CM risk 10x > for whites w/ CM risk 10x > for whites w/
DN.DN.►► CM risk 100% if CM risk 100% if DNDN pt. has pt. has
>2 first degree relatives w/ >2 first degree relatives w/ CM.CM.
Dysplastic NeviDysplasticDysplastic NeviNevi
PRECURSOR LESIONSPRECURSOR LESIONS
MelanomaMelanomaMelanomaCutaneousCutaneous
►► Nevus cells that reside Nevus cells that reside within the dermiswithin the dermis
►► SMALL BN (<0.5 cm)SMALL BN (<0.5 cm)appear in childhoodappear in childhoodextsexts. and dorsum of . and dorsum of handhandno assoc. w/ melanomano assoc. w/ melanoma►► LARGE CELLULAR BN (>1 LARGE CELLULAR BN (>1
cm)cm)nodular; trunknodular; trunkassoc. w/ melanomaassoc. w/ melanoma
Clin
ical
Pre
sent
atio
nC
linic
al P
rese
ntat
ion
Clin
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Pre
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atio
n
Blue NeviBlue NeviBlue Nevi
PRECURSOR LESIONSPRECURSOR LESIONS
MelanomaMelanomaMelanomaCutaneousCutaneous
Clin
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Pre
sent
atio
nC
linic
al P
rese
ntat
ion
Clin
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Pre
sent
atio
n CLINICOPATHOLOGIC TYPESCLINICOPATHOLOGIC TYPES
MelanomaMelanomaMelanomaCutaneousCutaneous
CLINICOPATHOLOGIC TYPESCLINICOPATHOLOGIC TYPES
MelanomaMelanomaMelanomaCutaneousCutaneousC
linic
al P
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ntat
ion
Clin
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Pre
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atio
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linic
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ion
Superficial SpreadingSuperficial SpreadingSuperficial Spreading
Superficial SpreadingSuperficial SpreadingSuperficial Spreading
Is this melanoma ?Is this melanoma ?
►► 48 48 yoyo femalefemale►► 2 yr 2 yr hxhx of pigmented of pigmented
plaqueplaque►► no personal or family no personal or family
hxhx of CMof CM►► PE otherwise normalPE otherwise normal
Pigmented Basal Cell Carcinoma
Pigmented Pigmented Basal Cell CarcinomaBasal Cell Carcinoma
Is this melanoma ?Is this melanoma ?
►► 52 52 yoyo hispanichispanic malemale►► 4.5 yr 4.5 yr hxhx of pigmented of pigmented
plaqueplaque►► no personal or family no personal or family
hxhx of CMof CM►► PE otherwise normalPE otherwise normal
Superficial SpreadingSuperficial SpreadingSuperficial Spreading
Is this melanoma ?Is this melanoma ?
►► 76 76 yoyo malemale►► >1 yr >1 yr hxhx of pigmented of pigmented
macular lesionmacular lesion►► sister w/ sister w/ hxhx of CMof CM►► PE otherwise normalPE otherwise normal
CLINICOPATHOLOGIC TYPESCLINICOPATHOLOGIC TYPESC
linic
al P
rese
ntat
ion
Clin
ical
Pre
sent
atio
nC
linic
al P
rese
ntat
ion
MelanomaMelanomaMelanomaCutaneousCutaneous
NodularNodularNodular
CLINICOPATHOLOGIC TYPESCLINICOPATHOLOGIC TYPESC
linic
al P
rese
ntat
ion
Clin
ical
Pre
sent
atio
nC
linic
al P
rese
ntat
ion
MelanomaMelanomaMelanomaCutaneousCutaneous
Lentigo MalignaLentigoLentigo MalignaMaligna
Lentigo MalignaLentigoLentigo MalignaMaligna
CLINICOPATHOLOGIC TYPESCLINICOPATHOLOGIC TYPESC
linic
al P
rese
ntat
ion
Clin
ical
Pre
sent
atio
nC
linic
al P
rese
ntat
ion
MelanomaMelanomaMelanomaCutaneousCutaneous
Acral LentiginousAcralAcral LentiginousLentiginous
Acral LentiginousAcralAcral LentiginousLentiginous
►► 71 71 yoyo white malewhite male►► >1.5 yr >1.5 yr hxhx of a of a
darkening pigmented darkening pigmented streak in nailstreak in nail
►► no family or personal no family or personal hxhx of CMof CM
►► PE otherwise normalPE otherwise normal
Is this melanoma ?Is this melanoma ?
Subungual HematomaSubungualSubungual HematomaHematoma
►► 26 26 yoyo malemale►► 6 week 6 week hxhx of of
pigmented nail pigmented nail ►► mother w/ mother w/ hxhx of CMof CM►► PE otherwise normalPE otherwise normal
Is this melanoma ?Is this melanoma ?
Acral Nodular CMAcralAcral Nodular CMNodular CM
►► 56 56 yoyo femalefemale►► <1 yr <1 yr hxhx of nodular of nodular
lesion; recent rapid lesion; recent rapid growthgrowth
►► no no hxhx of traumaof trauma►► no family or personal no family or personal
hxhx of CMof CM►► PE otherwise normalPE otherwise normal
Is this melanoma ?Is this melanoma ?
Pyogenic GranulomaPyogenicPyogenic GranulomaGranuloma
Amelanotic CMAmelanoticAmelanotic CMCMClin
ical
Pre
sent
atio
nC
linic
al P
rese
ntat
ion
Clin
ical
Pre
sent
atio
nMelanomaMelanomaMelanomaCutaneousCutaneous
CLINICOPATHOLOGIC TYPESCLINICOPATHOLOGIC TYPES
Contact DermatitisContact DermatitisContact Dermatitis
Amelanotic
Is this melanoma ?Is this melanoma ?►► 57 57 yoyo male executivemale executive►► 9 month 9 month hxhx of of
erythematouserythematous scaly plaqueplaque
►► cousin w/ cousin w/ hxhx of CMof CM►► PE otherwise normalPE otherwise normal
scaly
CMAmelanoticAmelanotic CMCM
►► Determine if the patient has a Determine if the patient has a personal or family history of: personal or family history of:
melanomamelanomaor melanoma precursor lesionsor melanoma precursor lesions
Wor
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Wor
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Wor
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HISTORYHISTORY
►► Careful documentation of lesions Careful documentation of lesions previously biopsied on patients.previously biopsied on patients.
►► If a biopsy is in question a reIf a biopsy is in question a re--evaluation of the specimen evaluation of the specimen should be performed by a should be performed by a recognized expert in melanoma recognized expert in melanoma histology.histology.
Is this melanoma ?Is this melanoma ?
Wor
kup
Wor
kup
Wor
kup
SKIN EXAMSKIN EXAMAny patient w/ melanoma or at Any patient w/ melanoma or at
risk for melanoma:risk for melanoma:►► A total body skin exam A total body skin exam
using good direct light.using good direct light.►► Examination aids Examination aids
((i.e.dermatoscopei.e.dermatoscope))►► All suspicious lesions should All suspicious lesions should
be carefully visualized, be carefully visualized, measured and documented measured and documented in the patient's medical in the patient's medical record.record.
MelanomaMelanomaMelanomaCutaneousCutaneous
Rol
e of
the
patie
ntR
ole
of th
e pa
tient
Rol
e of
the
patie
nt
►►Self exams (skin & lymph nodes) Self exams (skin & lymph nodes) twice a monthtwice a month
►►Follow up with physiciansFollow up with physicians►►Education of family membersEducation of family members
ABCDABCD’’ssEncourage frequent self skin Encourage frequent self skin examsexamsSkin exam by physicianSkin exam by physicianSunWiseSunWise behaviorsbehaviors
►► Prolonged Prolonged outdoor outdoor exposureexposure
►► Minimal Minimal protective protective clothingclothing
►► Improper use Improper use of sunscreenof sunscreen
►► Outdoor Outdoor activities activities between 10 between 10 am and 4 PMam and 4 PM
►► TanningTanning
UNWISE BEHAVIORS►► Hat w/ broad Hat w/ broad
brimbrim►► LongsleeveLongsleeve shirtshirt►► Long pantsLong pants►► Sunscreen on Sunscreen on
noncoverednoncoveredareasareas
►► Restrict outdoor Restrict outdoor activities to activities to early AM or late early AM or late afternoonafternoon
SUNWISE BEHAVIORSSUNWISE BEHAVIORS
MelanomaMelanomaMelanomaCutaneousCutaneous