CUTANEOUS MELANOMA

Click here to load reader

  • date post

    17-Jan-2016
  • Category

    Documents

  • view

    57
  • download

    0

Embed Size (px)

description

CUTANEOUS MELANOMA. 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. - PowerPoint PPT Presentation

Transcript of CUTANEOUS MELANOMA

  • MICHAEL STEFAN, M.D.SOUTHERN OHIO MEDICAL CENTERSCIOTO COUNTY MEDICAL SOCIETY2/19/10

  • MOLE OR MELANOMA: EARLY DETECTIONLIFETIME 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.*

  • A SIMPLE TOOL FOR EVALUATION OF MOLES.*

  • GROWTH PATTERNS OF MELANOMASUPERFICIAL SPREADING MELANOMA = 70%NODULAR MELANOMA = 20%LENTIGO MALIGNA MELANOMA = 10% IN ELDERLY POPULATION, MINIMAL PROPENSITY TO UNDERGO VERTICAL GROTH PHASE.CONGENITAL NEVIAMELANOTIC MELANOMAUNKNOWN PRIMARY70% OF MELANOMAS FROM PRE-EXISTING NEVUS.

    *

  • 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. *

  • FAMILIAL AND SYNDROMIC MELANOMAFAMILIAL 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.*

  • *

  • *

  • *

  • *METASATIC MELANOMA

  • LENTIGO MALIGNA MELANOMA*

  • RISK FACTORS: CONGENITAL HAIRY NEVUS*

  • MELANOMA RISK FACTORS*

  • PHENOTYPE 1*

  • PHENOTYPE 3*

  • *

  • THE EPIDERMAL MELANIN UNIT*

  • RISK FACTORS FOR MELANOMA : INTRINSICMELANOCYTE :MELANOSOME :SKINRETINAMUCOSAMENINGESFOUND IN THE EPIDERMAL KERATINOCYTEMSH-MELANIN STINULATING HORMONE DETERMINES PHENOTYPE OF PATIENTFITZPATRICK PHENOTYPE IS CLASSIFIED FROM TYPE 1 THRU 5.*

  • RISK FACTORS FOR MELANOMA : EXTRINSIC*

  • PLUS

    CUMULATIVE LIFETIME ULTRAVIOLET RADIATION

    EQUALS

    MELANOMA RISK

    NOTE: GREATER THAN FIVE CHILDHOOD BURNS !*CUTANEOUS MELANOMA

  • MELANOMA PROGRESSIONPUTATIVE STEPS IN PROGRESSION FROM A NORMAL MELANOCYTE TO MELANOMA: COMMON AQUIRED NEVUSDYSPLASTIC NEVUSINTRAEPITHELIAL PROLIFERATION OF ATYPICAL MELANOCYTESMELANOMA IN SITUSSMVERTICAL GROWTH PHASEMETASTATICONE OF THE BEST CHARECTERIZED GROWTH FACTORS FOR MELANOMA IS bFGF BASIC FIBROBLAST GROWTH FACTOR. SEVERAL MELANOMA CELL SURFACE MARKERS ARE PRESENT INCLUDING GANGLIOSIDE GD2AT 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*

  • MELANOMA: CLINICAL WORK-UPWORKUP: CXR AND CT/PET SCAN- BLOOD CHEMISTRIES.SERUM ALKALINE PHOSPHATASE AND LACTIC DEHYDROGENASE-PERHAPS OF HISTORICAL INTEREST ONLY.BRAIN CT OR MRIBONE SCANCONSULTATIONS 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.

    *

  • MICROSTAGING: HISTORY*

  • MELANOMA HISTORYHISTORICALLY, 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 TREATMENTTHE 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.

    *

  • MELANOMA MICROSTAGINGA 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*

  • *

  • 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

  • MICROSTAGING:*

  • *

  • 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.*

  • MULTIVARIATE ANALYSIS OF MELANOMAMULTIFACTORIAL 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.

    *

  • SURGICAL THERAPY*

  • EXCISIONAL BIOPSYFOLLOWING 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*

  • EXCISIONAL BIOPSY*

  • SURGICAL TREATMENTTHE 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. LYMPHOSCINTIGRAPHYMELANOMAS 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.

    *

  • WIDE LOCAL EXCISION OF AN INTERMEDIATE DEPTH MELANOMA:NOTE THE USE OF LYMPHAZURIN BLUE*

  • SENTINAL LYMPH NODE MAPPINGSPONTANEOUS 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