Transcript melanoma - Scioto County Medical Society

MICHAEL STEFAN, M.D.
SOUTHERN OHIO MEDICAL CENTER
SCIOTO COUNTY MEDICAL SOCIETY
2/19/10
MOLE OR MELANOMA: EARLY DETECTION
 LIFETIME RISK FOR THE DEVELOPMENT OF




MELANOMA IS 1 IN 40 FOR 2010; UP FROM 1 IN 1500 IN
THE 1935. ANNUAL NEW CASES ARE APPROXIMATELY
50,000.
IF SPREAD TO REGIONAL NODES ARE DISCOVERED,
ONLY ONE THIRD WILL BE CURED.
ABCDE-A=ASYMMETRY; B=BORDER IRREGULARITY;
C=COLOR VARIEGATION; D=DIAMETER >5MM AND E=
ELEVATION. THE COMMON DENOMINATOR IS THEIR
CHANGING NATURE WHICH SHOULD PROMPT
EXCISIONAL BIOPSY.
HIGH VIGILANCE AND A LOW THRESHOLD FOR
DERMATOLOGIC BIOPSY IS ESSENTIAL.
MOLES ARE A CLUSTER OF MELANOCYTES. MOST
PEOPLE HAVE 10 – 40 MOLES.
2
A SIMPLE TOOL FOR EVALUATION OF MOLES.
3
GROWTH PATTERNS OF MELANOMA
 SUPERFICIAL SPREADING MELANOMA = 70%
 NODULAR MELANOMA = 20%
 LENTIGO MALIGNA MELANOMA = 10% IN
ELDERLY POPULATION, MINIMAL PROPENSITY
TO UNDERGO VERTICAL GROTH PHASE.
 CONGENITAL NEVI
 AMELANOTIC MELANOMA
 UNKNOWN PRIMARY
 70% OF MELANOMAS FROM PRE-EXISTING
NEVUS.
4
HISTOLOGIC GROWTH PATTERNS OF MELANOMA:
 GROWTH PATTERNS; IMPORTANT BECAUSE THEY DETERMINE
PROGNOSIS AND ARE DIVIDED INTO 4 PATTERNS: 1. SSM 2. NM 3.LMM 4.
ACRAL LENTIGINOUS MELANOMA (ALM). 70% OF MELANOMAS ARE
SSM AND MOST ARISE IN A PRE-EXISTING NEVUS. NM ACCOUNTS FOR
15-30% AND FREQUENTLY EVOLVE DE NOVO, MORE COMMON IN MEN
AND AXIAL. LMMS CONSTITUTE 5% AND HAVE A LOW PROPENSITY FOR
METASTASIS AND ARE ON THE FACE IN ELDERLY INDIVIDUALS. .
UNCOMMON BEFORE AGE 50. ALMS OCCUR ON THE PALMS AND SOLES
AND NAILBEDS. THEY ARE MORE COMMON IN PHENOTYPES 3 AND 4 (
MEDITERRANIAN, LATIN AND AFRO-AMERICAN).WHILE ALM ARE RARE
THEY ARE AGGRESSIVE.
 BIOLOGY OF MELANOMA – LOCATED AT THE EPIDERMAL-DERMAL
JUNCTION, ARE OF NEURAL CREST ORIGIN AND ARE LOCATED ON THE
SKIN IN 90%. ABOUT 4% OF MELANOMAS HAVE NO KNOWN PRIMARY
SITE. THE TECHNIQUE OF MOLECULAR GENETICS HAVE BEEN USED TO
IDENTIFY THE GENE ENCODING TYRONINASE SPECIFICALLY EXPRESSED
IN MELANOCYTES. HMB-45 AND S-100 ARE HISTOLOGICAL MARKERS
USED TO I.D. MELANOMA.
5
FAMILIAL AND SYNDROMIC MELANOMA
 FAMILIAL MELANOMAS ARE UNCOMMON BUT
HAVE BEEN WELL DOCUMENTED . THIS IS A
AUTOSOMAL DOMINANT TRANSMISSION
ORIGINALLY TERMED THE B-K MOLE SYNDROME
AND NOW REFERRED TO AS THE DYSPLASTIC
NEVUS SYNDROME., FAMILIAL TYPE.
 MELANOMA SUSCEPTIBILITY GENES. 90% ARE
SPORADIC; 7% FAMILIAL AND 3% HEREDITARY,
THE HEREDITARY TYPE IS THE CDNK2A (P16)
GENE CONTROLLING CELL GROWTH.
6
7
8
9
METASATIC MELANOMA
10
LENTIGO MALIGNA MELANOMA
11
RISK FACTORS: CONGENITAL HAIRY NEVUS
12
MELANOMA RISK FACTORS
13
PHENOTYPE 1
14
PHENOTYPE 3
15
16
THE EPIDERMAL MELANIN UNIT
17
RISK FACTORS FOR MELANOMA
: INTRINSIC
MELANOCYTE :
MELANOSOME :
 SKIN
 FOUND IN THE
 RETINA
EPIDERMAL
KERATINOCYTE
 MSH-MELANIN
STINULATING HORMONE
DETERMINES PHENOTYPE
OF PATIENT
 FITZPATRICK PHENOTYPE
IS CLASSIFIED FROM TYPE
1 THRU 5.
 MUCOSA
 MENINGES
18
RISK FACTORS FOR MELANOMA : EXTRINSIC
19
CUTANEOUS
MELANOMA
PLUS
CUMULATIVE LIFETIME ULTRAVIOLET RADIATION
EQUALS
MELANOMA RISK
NOTE: GREATER THAN FIVE CHILDHOOD BURNS !
20
MELANOMA PROGRESSION
 PUTATIVE STEPS IN PROGRESSION FROM A NORMAL MELANOCYTE TO
MELANOMA: COMMON AQUIRED NEVUS…DYSPLASTIC
NEVUS…INTRAEPITHELIAL PROLIFERATION OF ATYPICAL
MELANOCYTES…MELANOMA IN SITU…SSM…VERTICAL GROWTH
PHASE…METASTATIC
 ONE OF THE BEST CHARECTERIZED GROWTH FACTORS FOR
MELANOMA IS bFGF BASIC FIBROBLAST GROWTH FACTOR. SEVERAL
MELANOMA CELL SURFACE MARKERS ARE PRESENT INCLUDING
GANGLIOSIDE GD2
 AT LEAST 4 DISTINCT GENES LOCATED ON CHROMOSOMES 1,6,7 AND 9
MAY PLAY A ROLE IN MELANOMA.POSSIBLY A COMPLEX SET OF
GENETIC EVENTS. CYTOGENIC ANALYSIS OF MELANOMA COULD BE
USEFUL IN PREDICTING CLINICAL COURSE.
 EXPOSURE TO SUNLIGHT IS CONSIDERED THE MAJOR CAUSE OF
MELANOMA. THE IMMUNE SYSTEM MAY BE DEPRESSED BY UVB RAYS.
HOWEVER, CUMULATIVE SUN EXPOSURE DOES NOT EXPLAIN ALL OF
THE BIOLOGIC BEHAVIOR OF MELANOMA. THE HIGHEST INCIDENCE
OF MELANOMA IS IN QUEENSLAND, AUSTRALIA
21
MELANOMA: CLINICAL WORK-UP
 WORKUP:
 CXR AND CT/PET SCAN- BLOOD CHEMISTRIES.
 SERUM ALKALINE PHOSPHATASE AND LACTIC






DEHYDROGENASE-PERHAPS OF HISTORICAL INTEREST ONLY.
BRAIN CT OR MRI
BONE SCAN
CONSULTATIONS BETWEEN ONCOLOGIST, RADIATION
THERAPIST, GENERAL SURGEON AND PLASTIC SURGEON.
PROGNOSTIC FACTORS; BALCH 8500 PATIENTS UNIVARIANT
AND MULTIVARIANT ANALYSIS FOR STAGE 1 AND 2 PRODUCING
A RELATIONSHIP BETWEEN TUMOR THICKNESS AND 10 YEAR
MORTALITY.
FOLLOW-UP EVERY 6 MONTHS.
RECURRENCE CAN OCCUR AS LATE AS 20 YEARS FOLLOWING
PRIMARY DIAGNOSIS.
22
MICROSTAGING: HISTORY
23
MELANOMA HISTORY
 HISTORICALLY, THE FIRST PUBLISHED PATIENT WITH




MELANOMA WAS BY JOHN HUNTER IN 1787. THE PATIENT WAS A
35 YEAR-OLD MALE.
RENE LAENNEC FIRST DESCRIBED MELANOMA AS A DISEASE
ENTITY IN 1806. ( THEREFORE, NEARLY 200 YEARS OF
UNDERSTANDING THE DISEASE.)
BIOLOGY, NATURAL HISTORY AND TREATMENT
THE CURRENT 5 YEAR SURVIVAL RATE OF 84% REPRESENTS A
MARKED IMPROVEMENT OVER THE 60% RATE FOR THE YEAR
1960.
DYSPLASTIC NEVI ARE LARGER (>6MM ) THAN COMMON
MELANOCYTIC NEVI AND THEIR PRESENCE SUGGESTS AN
INCREASED INCIDENCE OF MELANOMA, EITHER IN THE
DYSPLASTIC NEVUS OR IN UNINVOLVED SKIN.
24
MELANOMA MICROSTAGING
 A MALIGNANT TUMOR OF MELANOCYTES, CELLS THAT ARE





DERIVED FROM THE NEURAL CREST.
PREDOMINANTLY OCCUR IN ADULTS.
EARLY SIGNS IN A NEVUS INCLUDE DARKER OR VARIABLE
DISCOLORATION, INTERVAL INCREASE IN SIZE, NODULARITY
AND SYMPTOMATOLOGY; ITCHING, ULCERATION OR BLEEDING.
EXCISIONAL BIOPSY IS REQUIRED. THERE IS NO ROLE FOR
INCISIONAL BIOPSY OR SHAVE BIOPSY AND AN EXPERIENCED
DERMATOPATHOLOGIST IS REQUIRED FOR PROPER
MICROSTAGING.
PROGNOSIS IS AFFECTED BY CLINICAL AND HISTOLOGIC
FACTORS.
HISTOLOGIC FEATURES; THICKNESS OR LEVEL OF INVASION,
MITOTIC INDEX, PRESENCE OF TUMOR INFILTRATING
LYMPHOCYTES, SATELITOSIS
25
26
MICROSTAGING
 DISTINGUISHING BETWEEN A BENIGN PIGMENTED
LESION AND EARLY MELANOMA CAN BE DIFFICULT,
AND EVEN EXPERIENCED DERMATOPATHOLOGISTS
CAN HAVE DIFFERING OPINIONS.
 THE MICROSTAGE OF MELANOMA IS DETERMINED BY
2 CLASSIFICATIONS ON HISTOLOGIC EXAMINATION.
THE VERTICAL THICKNESS (BRESLOW) AS MEASURED
BY A MICROMETER AND THE LEVEL OF INVASION
WITHIN THE VARIOUS DERMAL LAYERS ( CLARK).
 PATHOLOGIC STAGING INCLUDES MICROSTAGING OF
THE PRIMARY MELANOMA AND PATHOLOGIC
INFORMATION REGARDING THE REGIONAL LYMPH
NODES AFTER SENTINAL NODE BIOPSY AND/OR
LYMPHADENECTOMY.
 DISCUSSION REGARDING MICROSTAGING
27
MICROSTAGING:
28
29
CLARK AND BRESLOW CLASSIFICATIONS:
 CLARK CLASSIFICATION BASED ON DEPTH OF PENETRATION
INTO PAPPILARY AND RETICULAR DERMIS. A MELANOMA
BECOMES MALIGNANT WHEN IT PENETRATES THE BASEMENT
MEMBRANE. THE SPREAD OF MELANOMA OCCURS IN THE
SUPERFICIAL SUBCUTANEOUS TISSUE WHERE THE LYMPHATIC
DRAINAGE IS LOCATED.
 BRESLOW CLASSIFICATION- LESS SUBJECTIVE, MICROMETER IS
USED TO MEASURE FROM THE GRANULAR LAYER TO THE
DEEPEST POINT OF PENETRATION OF TUMOR CELLS.
 BOTH CLASSIFICATIONS ARE REPORTED IN PATHOLOGY
REPORT.
30
MULTIVARIATE ANALYSIS OF MELANOMA
 MULTIFACTORIAL ANALYSIS-THICKNESS OF
MELANOMA, ULCERATION, ANATOMIC
LOCATION APPEAR TO BE THE MOST
IMPORTANT. SEX, AGE AND TUMOR
CHARACTERISTICS ALSO IMPORTANT.
 HISTOLOGIC TUMOR CHARACTERISTICS OF
LYMPHOCYTE INVASION, MICROSCOPIC
SATELLITES, MITOTIC ACTIVITY AND LEVEL OF
INVASION.
31
SURGICAL THERAPY
32
EXCISIONAL BIOPSY
 FOLLOWING EXCISIONAL BIOPSY, THIN MELANOMAS
( < .76 mm ) ARE SURGICALLY TREATED WITH A 1.0 CM
RADIAL EXCISION MARGIN. INTERMEDIATE DEPTH
LESIONS ( .75 TO 2.0 mm ) ARE TREATED WITH A 2.0
RADIAL EXCISION. SOMEWHAT CONTROVERSIAL,
PRIMARY LESIONS 2.0 TO 4 mm CAN BE TREATED
WITH A 2.0 CM RADIAL EXCISION. MORE RADICAL
TREATMENT OF THE PRIMARY SITE PROBABLY DOES
NOT CONFER A SURVIVAL ADVANTAGE. LESIONS
GREATER THAN 4 mm REQUIRE EXCISIONAL BIOPSY
ONLY AND FURTHER THERAPY IS AIMED AT SYSTEMIC
CONTROL BASED ON THE HIGH PREVELANCE OF
ESTABLISHED SYTEMIC METASTASIS
33
EXCISIONAL BIOPSY
34
SURGICAL TREATMENT
 THE CORRECT SURGICAL TECHNIQUE FOR TREATMENT OF THE PRIMARY
LESION INCLUDES A COMPOSITE RESECTION OF SKIN AND SUBCUTANEOUS FAT
WITH PRESERVATION OF THE UNDERLYING FASCIA OR MUSCLE. REGARDLESS OF
ANATOMIC LOCATION, FLAP RECONSTRUCTION OF THE POST-SURGICAL SITE IS
PREFERRED. THERE IS NO ROLE FOR SKIN GRAFTING IN THIS REGARD.
 PRIOR TO RESECTION OF THE PRIMARY LESION, ACCURATE IDENTIFICATION OF
POTENTIALLY INVOLVED NODAL BASINS IS REQUIRED. LYMPHOSCINTIGRAPHY
 MELANOMAS THAT HAVE A THICKNESS GREATER THAN 4.0 mm SHOULD BE
CONSIDERED FOR ADJUVANT THERAPY WITH HIGH DOSE INTERFERON. TO
DATE, THREE WELL DESIGNED PROSPECTIVE, RANDOMIZED CONTROLLED
TRIALS DEMONSTRATED BOTH A DISEASE-FREE AND OVERALL SURVIVAL
ADVANTAGE WITH INTERFERON WHEN COMPARED TO OBSERVATION OR
ALTERNATE GANGLIOSIDE VACCINE.
 ADJUNCTIVE CHEMOTHERAPY WITH MELPHALAN DOES NOT IMPROVE
SURVIVAL . THE ONLY POTENTIAL DURABLE RESPONSE TO DISSEMINATED
MELANOMA IS HIGH-DOSE INTERLEUKIN-2 (IL-2).
 ALL PATIENTS WITH DISTANT METASTASIS ARE APPROPRIATELY CONSIDERED
CANDIDATES FOR CLINICAL TRIALS EXPLORING NEW FORMS OF TREATMENT
SUCH AS COMBINATION CHEMOTHERAPY, MONOCLONAL ANTIBODIES, IL-2,
INTERFERONS, VACCINE IMMUNOTHERAPY AND BIOCHEMOTHERAPY.
35
WIDE LOCAL EXCISION OF AN INTERMEDIATE DEPTH MELANOMA:
NOTE THE USE OF LYMPHAZURIN BLUE
36
SENTINAL LYMPH NODE MAPPING
 SPONTANEOUS REGRESSION OF MELANOMA IS SEEN IN LESS THAN 1%.
 INTERMEDIATE THICKNESS IS >.75 TO 2mm IN DEPTH. REGARDLESS OF
THE BRESLOW DEPTH OF THE PRIMARY LESION IT IS SAFE TO SAY THAT
ALL LESIONS CAN BE ADEQUATELY TREATED WITH A 2CM RADIAL
MARGIN. ELECTIVE REGIONAL LYMPH NODE DISSECTION IS OF NO
PROVEN BENEFIT IN STAGE 1 MELANOMA. HOWEVER, LYMPHATIC
MAPPING AND SENTINAL LYMPH NODE BIOPSY FOR PATIENTS WHO
HAVE TUMORS OF INTERMEDIATE THICKNESS MAY IDENTIFY THOSE
PATIENTS WHO MAY BENEFIT FROM THERAPEUTIC
LYMPHADENECTOMY.
 ALTHOUGH PROPHYLACTIC REGIONAL LYMPH NODE DISSECTIONS
HAVE BEEN USED IN PATIENTS WITH STAGE 11 MELANOMAS, 4
PROSPECTIVE RANDOMIZED TRIALS HAVE FAILED TO SHOW A
SURVIVAL BENEFIT. IN FACT, TO DATE ELND AND TLND HAVE
UNIVERSALLLY FAILED TO ABATE DISEASE PROGRESSION.
FURTHERMORE, UNLIKE BREAST CANCER WHEREIN NODE DISSECTION
IS OF VALUE FOR STAGING ONLY, RADICAL LYMPHADENECTOMY
CARRIES A SIGNIFICANT OCCURRENCE OF PATIENT MORBIDITY.
37
SENTINAL LYMPH NODE MAPPING: GAMMA
DETECTION
38
SENTINAL LYMPH NODE MAPPING
39
SENTINAL LYMPH NODE MAPPING
40
SAPPY’S LINE: OF HISTORICAL IMPORTANCE ONLY
41
THIS WILL IDENTIFY THE NODAL BASIN(S) THE
MELANOMA IS DRAINING TO AND DIRECT THE SURGEON
IN OBTAINING A SENTINAL NODE.
FROZEN SECTION HISTOPATHOLOGY CANNOT BE
PERFORMED ON THE PRIMARY LESION OR NODE.
THE FALSE NEGATIVE RATE FOR SENTINAL NODE BIOPSY
IS 3%.
42
43
SENTINAL LYMPH NODE BIOPSY
 THE DIAGNOSTIC ACCURACY OF SENTINAL LYMPH NODE
BIOPSY (SLNB) HAS BEEN DEMONSTRATED IN SEVERAL
STUDIES., WITH A FALSE NEGATIVE RATE <2%. USING A VITAL
BLUE DYE AND A RADIOPHARMACEUTICAL AGENT INJECTED AT
THE SITE OF THE PRIMARY TUMOR. THE FIRST LYMPH NODE
THAT DRAINS THE NODAL BASIN CAN BE IDENTIFIED AND
EXAMINED FOR MICROMETASTASIS. IF MICROMETASTASIS IS
FOUND BY THE DERMATOPATHOLOGIST, ELND CAN BE
PERFORMED. HOWEVER, THERE IS NO PROVEN SCIENTIFIC
EVIDENCE THAT ELND IN THE SETTING OF MICROMETASTASIS
WILL IMPROVE DISEASE FREE SURVIVAL. THESE PATIENTS MAY
BENEFIT FROM INTERFERON THERAPY AND IT IS PERHAPS HERE,
THAT SLNB IS OF VALUE.
 THE OVERALL MEDIAN SURVIVAL FOR PATIENTS TREATED WITH
HIGH DOSE INTERFERON WHEN COMPARED WITH CONTROLS
IS 3.8 YEARS.
44
SENTINAL LYMPHADENECTOMY IN CUTANEOUS
THIN MELANOMAS :
RICHARD BLEICHER, JOHN WAYNE CANCER INSTITUTE
 HIGHLY ACCURATE AND MINIMALLY MORBID
 FOLLOWING LYMPHOSCINTIGRAPHY, LYMPHATIC
MAPPING AND SENTINAL LYMPADENECTOMY (LM/SL)
WAS PERFORMED USING BLUE DYE ALONE OR WITH
RADIOPHARMACEUTICAL
 512 PATIENTS INSTITUTIONAL REVIEW FROM 19852000.
 THE RATE OF SN POSITIVE WAS 7.1% IN LESIONS
BETWEEN 1.01 AND 1.5mm. FOR THE 272 PATIENTS
WITH LESIONS < 1.00mm 2.9% WERE SN POSITIVE
AND 1.7% OF PATIENTS WITH LESIONS < .75 mm HAD
NODAL METS. PATIENTS WITH POSITIVE NODES
TENDED TO BE YOUNGER
45
SENTINAL LYMPHADENECTOMY IN CUTANEOUS
THIN MELANOMAS
:
RICHARD BLEICHER, JOHN WAYNE CANCER INSTITUTE
 CONCLUSIONS; LM/SL IS INDICATED IN ALL
PRIMARY LESIONS > 1mm AND YOUNG AGE MAY
CORRELATE WITH NODAL METS IN LESIONS < 1.0
mm. FOR LESIONS <.75 LM/SL IS RARELY
INDICATED, HOWEVER, SHOULD BE CONSIDERED
IN NODULAR PRIMARY AND IN YOUNG AGE, (<40
YEARS OLD)
46
CUTANEOUS MELANOMA
 CASE STUDIES
47
SUPERFICIAL SPREADING MELANOMA 1.7MM
BRESLOW DEPTH
48
WLE WITH RHOMBOID FLAP RECONSTRUCTION
49
FACIAL MELANOMA
SSM- “FIELD OF FIRE”
DISSECTION WITH MUSTARDE
FLAP
50
FACIAL MELANOMA
51
INTERMEDIATE DEPTH SSM OF EARLOBE
52
EARLOBE RECONSTRUCTION AND NECK DISSECTION
53
A FARMER FROM IOWA PRESENTS TO OFFICE
54
SIX MONTHS FOLLOWING RADICAL NODE
DISSECTION WITH RECURRENCE
55
THERAPEUTIC NODE DISSECTION
56
THERAPEUTIC NODE DISSECTION
 IN STAGE 3, PATIENTS WITH ENLARGED NODES HAVE A 85%
CHANCE OF HARBORING DISTANT METS AND A SURVIVAL RATE
OF <10% AT 10 YEARS.
 THE PATIENT SHOWN, DIED 6 MONTHS LATER WITH
CHEMOTHERAPY.
57
VISCERAL METASTASES
58
ELECTIVE NODE DISSECTION: PRIOR TO KNOWN
NODAL METASTASES
 IN STAGE 3 MELANOMA (BY DEFINITION, LIMITED NODAL METS)
THE NUMBER OF INVOLVED NODES IS IMPORTANT.
 ELND- THE WHO PROSPECTIVE NONRANDOMIZED STUDY OF
1319 IMPROVED SURVIVAL OF INTERMEDIATE THICKNESS. AT
UAB 676 PTS WITH INTERMEDIATE THICKNESS (1.5-4.0) ALSO
IMPROVED SURVIVAL.

 THERE HAVE BEEN NO RANDOMIZED PROSPECTIVE TRIALS
INDICATING SURVIVAL STATISTICS FOR ELND OF AXIAL
MELANOMAS.
 THE MAYO CLINIC AND WHO MELANOMA GROUP STUDIES
INDICATED NO BENEFIT FROM ROUTINE ELND FOR PATIENTS
WITH STAGE1 AND 2 EXTREMITY MELANOMAS
59
HOW IS MELANOMA STAGED ?
 STAGING SYSTEM ADOPTED BY THE AMERICAN
JOINT COMMITTEE ON CANCERIS BASED ON
TUMOR MICROSTAGING OF THE PRIMARY
LESION
 REGIONAL NODAL BASINS ARE THE MOST LIKELY
SITE TO HARBOR SPREAD FOLLOWED BY
REGIONAL SKIN (SATELLITOSIS) SUBCUTANEOUS
SKIN AND LUNG. COMMON METASTATIC SITES
ARE THE LIVER, BRAIN AND BONE.
60
HOW IS MELANOMA STAGED ?
61
HOW IS MELANOMA STAGED ?
62
CUTANEOUS MELANOMA?
ADJUVANT THERAPY
63
ADJUVANT THERAPY IN STAGE 3 AND 4 MELANOMA
SOMETHING THAT ENHANCES THE EFFECTIVENESS OF MEDICAL THERAPY
 CLINICAL BENEFIT OF CYTOTOXIC T LYMPHOCYTES (CTL)
 CHEMOTHERAPY
 VACCINES—ALLOGENIC AND AUTOLOGOUS CELLULAR VACCINES,
CARBOHYDRATE VACCINES, DNA VACCINES, PEPTIDE VACCINES AND
HEAT-SHOCK PROTEIN VACCINES.
 MELANOMA, THE MOST FATAL FORM OF SKIN CANCER, IS RISING AT A
RATE FASTER THAN ALL PREVENTABLE CANCERS EXCEPT LUNG CANCER
IN THE UNITED STATES. “WE” EVALUATED THE EPA’S SUNWISE SCHOOL
PROGRAM FOR SUN SAFETY FOR CHILDREN. RESULTS: STANDARDIZED
SUN PROTECTION EDUCATION CAN BE EFFICIENTLY INTERWOVEN
INTO SCHOOL HEALTH EDUCATION AND RESULT IN IMPROVEMENTS
IN KNOWLEDGE AND POSITIVE INTENTIONS FOR SUN PROTECTION.
 MELANOMA INCIDENCE IS RISING 7% PER YEAR
64
ADJUVANT THERAPY IN STAGE 3 AND 4 MELANOMA
SOMETHING THAT ENHANCES THE EFFECTIVENESS OF MEDICAL THERAPY
 VACCINES—ALLOGENIC AND AUTOLOGOUS
CELLULAR VACCINES, CARBOHYDRATE VACCINES,
DNA VACCINES, PEPTIDE VACCINES AND HEAT-SHOCK
PROTEIN VACCINES.
65
ADJUVANT THERAPY IN STAGE 3 AND 4 MELANOMA
CHEMOTHERAPY; INTERFERON
 THERE ARE NO PROVEN TREATMENT REGIMENS THAT SIGNIFICANTLY
REDUCE THE LIKELYHOOD OF RECURRENT DISEASE.
 IMMUNOTHERAPY- WHILE TOXIC EFFECTS OF HIGH DOSE IL-2 ARE
SEVERE, SIG. RESPONSE RATES HAVE BEEN REPORTED.
 MONCLONAL ANTIBODY- MONOCLONAL ANTIBODIES ARE TARGETED
AS ANTIGENS EXPRESSED ON THE SURFACE OF MELANOMA. THESE
ANTIBODIES CAN BE USED TO ACTIVATE THE HOST IMMUNE SYSTEM
OR CONJUGATED TO A CYTOTOXIC AGENT.
66
CHEMOTHERAPY
 CONVENTIONAL CHEMOTHERAPY (CYTOTOXIC
DRUGS) IN THE TREATMENT OF MALIGNANT
MELANOMA HAS BEEN DISAPPOINTINGLY
INEFFECTIVE.
 ONE OF THE MOST EFFECTIVE AGENTS IS
DACARBAZIDE. WHY? THE BASIS FOR DRUG
RESISTANCE IN MELANOMA IS MOST LIKELY
DYSREGULATION OF APOPTOSIS, ALTHOUGH OTHER
MECHANISMS SUCH AS DRUG TRANSPORT,
DETOXIFICATION AND ENHANCED DNA REPAIR MAY
ALSO PLAY A ROLE. AN INHIBITOR OF APOPTOSIS,
SURVIVIN, IS EXPRESSED IN MELANOMA AND
REQUIRED FOR CELL VIABILITY. TARGETING OF
SURVIVIN AND OTHER APOPTOTIC REGULATORS
INCREASES THE SENSITIVITY OF MELANOMA CELLS
TO CYTOTOXIC DRUGS.
67
MELANOMA CHEMOTHERAPY
 CHEMOTHERAPY – FOR PAST 20 YEARS,
DICARBAZINE (DTIC) WITH RESPONSE RATES
OF < 20%. COMPLETE REMISSION IN < 5% OF
PATIENTS. THE COMBINATION OF DTIC,
CARMUSTINE, CISPLATIN, AND TAMOXIFEN
RESPONSE RATE OF 50% AND A WITH A
MEDIAN SURVIVAL OF RERSPONDERS + 10
MONTHS.

68
CUTANEOUS MELANOMA
 MOLECULAR AND GENETIC LESIONS
UNDERLYING MELANOMA
69
THIS IS THE FUTURE OF MELANOMA
TPREVENTION AND TREATMENT:
AS WITH ALL CANCERS WE ARE LOOKING AT
THEMOLECULAR BIOLOGY, PATIENT PHENOTYPE
AND CELLULAR MANIPULATION.
70
71
IMPORTANT GENES IN MELANOMA
72
MELANOMA PREVENTION
 MELANOMA, THE MOST FATAL FORM OF COMMON
SKIN CANCER, IS RISING AT A RATE FASTER THAN ALL
PREVENTABLE CANCERS EXCEPT LUNG CANCER IN
THE UNITED STATES.
 “WE” EVALUATED THE EPA’S SUNWISE SCHOOL
PROGRAM FOR SUN SAFETY FOR CHILDREN. RESULTS:
STANDARDIZED SUN PROTECTION EDUCATION CAN
BE EFFICIENTLY INTERWOVEN INTO SCHOOL BASED
EDUCATION PROGRAMS.
 TANNING BEDS – ONCOLOGIC AND AESTHETIC
NO WIN !
73
CUTANEOUS MELANOMA: QUESTIONS ?
74