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  • Figure 2. Relationship between the Stage of Melanoma and Survival.
    Kaplan-Meier survival curves are adapted from the American Joint Committee on Cancer.23
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    1. 1. An Overview of MelanomaAn Overview of Melanoma Harriet Kluger, M.D.Harriet Kluger, M.D. Associate ProfessorAssociate Professor Section of Medical OncologySection of Medical Oncology Yale Cancer CenterYale Cancer Center
    2. 2. Melanoma StatisticsMelanoma Statistics  Median age at presentation – 45-55 yearsMedian age at presentation – 45-55 years  Incidence: 2003 – 54,200 casesIncidence: 2003 – 54,200 cases  2008 (projected) - 62,4802008 (projected) - 62,480  66thth among menamong men  77thth among womenamong women  Increasing in incidence in men and womenIncreasing in incidence in men and women  Mortality (2003) – 7600 patients, (2008) – 8420Mortality (2003) – 7600 patients, (2008) – 8420 projected deathsprojected deaths  1 in 17 white Australian males1 in 17 white Australian males
    3. 3. Melanoma tumor formationMelanoma tumor formation Bar-Eli M. Gene regulation in melanoma progression by the AP-2 transcription factor. Pigment Cell Res. 2001 Apr;14(2):78-85. Review. Normal Benign/premalignant Malignant / Locally Invasive Metastasis Normal Melanocytes Dysplastic Nevi Early Primary Radial Growth Phase Advanced Primary Vertical Growth Phase Metastatic Melanoma p16 Integrins p53 c-kit ↓ E-cadherin ↓ N-cadherin ↑ MUC18/MCAM ↑ CREB/ATF-1 ↑ Angiogenesis, Invasion & Apoptosis: e.g., bFGF, IL-8, MMP-2, EGF-R, PAR-1, FAS/APO-1
    4. 4. Risk Factors for MelanomaRisk Factors for Melanoma  Genetics & EnvironmentGenetics & Environment  Race (Caucasians 5-20 fold increased risk overRace (Caucasians 5-20 fold increased risk over Africans, East Asians, Hispanics)Africans, East Asians, Hispanics)  Geographic location (proximity to equator)Geographic location (proximity to equator)  Genetic Factors & RiskGenetic Factors & Risk  Skin pigmentation and propensity for sunburnSkin pigmentation and propensity for sunburn  Family history of melanomaFamily history of melanoma  Density and type of nevi (common, ‘atypical’)Density and type of nevi (common, ‘atypical’)  Genetic mutations: p16, CDK4Genetic mutations: p16, CDK4  Environmental FactorsEnvironmental Factors  Recreational and occupational sun exposureRecreational and occupational sun exposure  Ozone depletionOzone depletion
    5. 5. ABCDE of diagnosisABCDE of diagnosis  A:A: AAssymetryssymetry  B:B: BBorder irregularityorder irregularity  C:C: CColor - unusual or changingolor - unusual or changing  D:D: DDiameter > 6mmiameter > 6mm  E:E: EEvolution orvolution or EElevationlevation  ? F:? F: FFunny lookingunny looking
    6. 6. Changing or new moles Variation in color Irregular borders
    7. 7. The Pigmented Cell/MelanocyteThe Pigmented Cell/Melanocyte  Neural crest origin in embryonal lifeNeural crest origin in embryonal life  Function: synthesis, storage, and transferFunction: synthesis, storage, and transfer of melanin (pigment) to surrounding cellsof melanin (pigment) to surrounding cells  Melanoma occurs anywhere melanocytesMelanoma occurs anywhere melanocytes are foundare found
    8. 8. Melanoma subtypesMelanoma subtypes  Superficial spreadingSuperficial spreading: most common form,: most common form, often arise in preexisting moles, mostly onoften arise in preexisting moles, mostly on the extremities, bleed, more common inthe extremities, bleed, more common in womenwomen
    9. 9. Nodular melanomaNodular melanoma  15% of melanomas15% of melanomas  dome shapeddome shaped  uniform color, like blood blistersuniform color, like blood blisters  Younger patientsYounger patients  usually no prior mole in that areausually no prior mole in that area
    10. 10. Acral lentiginous melanomaAcral lentiginous melanoma  palms, soles, nailbedspalms, soles, nailbeds  Often thick and wideOften thick and wide  Males > femalesMales > females  Most common type in blacks andMost common type in blacks and hispanicshispanics
    11. 11. Lentigo Maligna MelanomaLentigo Maligna Melanoma  5-10% of melanomas5-10% of melanomas  Often on face and neckOften on face and neck  More common in the “elderly” (Median age 62)More common in the “elderly” (Median age 62)  Females > MalesFemales > Males  flat, grow very fast, rarely metastasize to internal organsflat, grow very fast, rarely metastasize to internal organs
    12. 12. Desmoplastic melanomasDesmoplastic melanomas  rarerare  Often in “elderly” (6Often in “elderly” (6thth or 7or 7thth decade)decade)  Often amelanotic (without pigment)Often amelanotic (without pigment)  Tend to grow on nervesTend to grow on nerves
    13. 13. Non-cutaneous MelanomaNon-cutaneous Melanoma (rare)(rare)  Ocular melanoma, mostly choroid andOcular melanoma, mostly choroid and ciliary bodyciliary body  Mucosal melanoma: Head and neckMucosal melanoma: Head and neck Vulva and vaginaVulva and vagina AnalAnal Female urethraFemale urethra EsophagusEsophagus
    14. 14. Multi-disciplinary therapeutic approach to melanoma Dermatopathology Dermatologist or Primary Care Physician Plastic or dermatologic surgery Pathology Radiology Medical Oncology Radiation oncologist (for palliation)
    15. 15.  Initial diagnosis by dermatologist or primary care doctorInitial diagnosis by dermatologist or primary care doctor  Vast majority present with resectable primary skin melanoma andVast majority present with resectable primary skin melanoma and majority are cured by resection alonemajority are cured by resection alone  Relatively few have lymph node disease at the time of diagnosisRelatively few have lymph node disease at the time of diagnosis  Metastases detected months to many years laterMetastases detected months to many years later  Patients can develop metastatic disease in almost any site, treatedPatients can develop metastatic disease in almost any site, treated with surgery when resectable or “systemic therapy” (by mouth or IV)with surgery when resectable or “systemic therapy” (by mouth or IV)  High propensity for brain metastases, which require radiationHigh propensity for brain metastases, which require radiation therapytherapy Therapeutic approach to melanoma
    16. 16. Clinical Staging of Melanoma toClinical Staging of Melanoma to Assess the PrognosisAssess the Prognosis  Depth of primary lesionDepth of primary lesion  Microscopic ulceration of primary lesionMicroscopic ulceration of primary lesion  Regional lymph node involvementRegional lymph node involvement  Presence or absence of in-transitPresence or absence of in-transit metastasesmetastases  Presence or absence of distantPresence or absence of distant metastases (in other organs)metastases (in other organs)
    17. 17. Tsao, H. et al. N Engl J Med 2004;351:998-1012 Relationship between Stage of Melanoma and Survival + nodes + Blood-borne metastases
    18. 18. Other important predictors of survivalOther important predictors of survival  Location of the melanoma (Trunk vs.Location of the melanoma (Trunk vs. extremity)extremity)  AgeAge  SexSex  Most important prognostic markers –Most important prognostic markers – depth of skin lesion, lymph nodedepth of skin lesion, lymph node involvement and presence of ulcerationinvolvement and presence of ulceration
    19. 19. Topics to be covered – patient careTopics to be covered – patient care  Risk factors, sun exposure and prevention (Dr. Leffell,Risk factors, sun exposure and prevention (Dr. Leffell, Dermatology)Dermatology)  Skin cancer screening and diagnosis of melanoma (Dr.Skin cancer screening and diagnosis of melanoma (Dr. Bolognia, Dermatology)Bolognia, Dermatology) Dermatopathology Dermatologist or Primary Care Physician Plastic or dermatologic surgery Pathology Radiology Medical Oncology Radiation oncologist (for palliation)
    20. 20. Surgical resection (Dr. Ariyan)Surgical resection (Dr. Ariyan) Drug treatments for prevention of treatmentDrug treatments for prevention of treatment of metastatic disease (Dr. Sznol)of metastatic disease (Dr. Sznol) Dermatopathology Dermatologist or Primary Care Physician Plastic or dermatologic surgery Pathology Radiology Medical Oncology Radiation oncologist (for palliation)
    21. 21. Our other mission - research toOur other mission - research to improve outcomeimprove outcome  Target populations:Target populations: a) patients at high risk for metastatic diseasea) patients at high risk for metastatic disease (understand what makes some melanomas(understand what makes some melanomas metastasize)metastasize) b) Patients with metastatic disease – developb) Patients with metastatic disease – develop novel drugs that attack the melanoma cells ornovel drugs that attack the melanoma cells or enhance the immune system to attack thoseenhance the immune system to attack those cellscells  Dr. HalabanDr. Halaban  Dr. SznolDr. Sznol

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