Malignant Melanoma Juraj Hegyi LF MU lOriginates from melanocytes lMelanin producing cells lBasal membrane, hair follicules l8 most common malignant tumor in CR lIn the last 30 years 4x increased incidence l2500 new cases per annum (450 deaths) lEvery 4 diagnosed patient <50r. lCca 25.000 patients with dg. MM in anamn. lMalignant melanoma is usually diagnosed early approx. 85% lHigh 5 year survival rate lStage I. – 90/100 patients lStage IV. - 15/100 patients lCharacteristic horizontal growth phase followed by penetrating vertical phase lMost cases Sweden, Estonia, Denmark, Holand and Australia. Standardized mortality of MM per 100 000 capita lGenetics -Mutation of CDKN2A, CDK4, MCN1 -Aneuploidia of chromosomes 1,6,7,9,10,11 -BRAF, N-RAS mutations lEnviromental factors (UVA, UVB) -Intermittent sun exposure (short but intensive) ↑ -Long term sun exposure (slow but steady) ↓ -Solariums +/- lSensibilisation -Plants (furocoumarines, lime) -Tar -Medication (furosemide, diclofenac, TTC, ketoprofen) lImunosupression -Transplanted patients -Systemic treatment of autoimmune diseases lEthnicity -Pale skin (phototype I. a II.)Pigmented nevi -↓ incidence in darker skin Most common forms of MM lSuperficial spreading melanoma (SSM) lNodular melanoma (NMM) lAcral lentiginous melanoma (ALM) lLentigo maligna melanoma (LMM) Rarer types of MM lAmelanotic melanoma lNevoid melanoma lMalignant blue nevi lDesmoplastic melanoma lMucous membrane melanoma lOccular melanoma lJuvenile melanoma Superficial spreading melanoma (SSM) lMost common form (approx. 70%) lOften between 3 and 5 decade lWomen most often feet lMen most often upper body lDepigmentation (regression) – signs of interaction with immune system Superficial spreading melanoma (SSM) Superficial spreading melanoma (SSM) Nodular melanoma (NMM) l15-30% of all melanomas lOften in 6 decade of life lChest, neck, face lBlue or black nodules lOften without horizontal phase Nodular melanoma (NMM) Acral lentiginous melanoma (ALM) lLess common form of melanoma (5-10%) lMost common form in asians and blacks (45%/70%) lPalms, souls of feet, nails lDue to location hard to diagnose Acral lentiginous melanoma (ALM) Acral lentiginous melanoma (ALM) Lentigo maligna melanoma (LMM) lApprox. 15% of all melanoma lLocations of chronic sun damage lUsually 7 decade of life lMost often head, face and nose lDifferential diagnosis with sun damage Lentigo maligna melanoma (LMM) Amelanotic melanoma lRare form of pigmented -Approx. 2-20% of all diagnosed melanomas lOften misdiagnosed (BCC, verruca, fibroma) lVery hard to diagnose (3R method) -Raised -Red -Recent Amelanotic melanoma Diagnosis of MM lClinical image (ABCDEF rule) lMedical history lDermoscopy lHistological examination (excision/biopsy) -“When in doubt, cut it out” lFISH – detection of chromosomal aberrations Non invasive diagnosis Breslow scale Breslow thickness is the measurement of the depth of the melanoma from the surface of the skin down through to the deepest point of the tumour. Stratum granulosum Clark scale lI. Only epidermis (Carcinoma in situ) lII. down to papillary dermis lIII. papillary dermis involvement without reticular dermis invasion lIV. reticular dermis involvement without subcutis invasion lV. Da full monty Metastasis lLymphogenic a hematogenic spread lMost often lungs, liver, brain, bones lSatellites (2 cm from tumor) lIntransit (more then 2 cm from tumor) lNodal (regional lymph nodes) lMelanosis cutis diffusa Metastasis Primary therapy lWide excision (safety margin) -MM in situ – 0.5 cm -MM up to Breslow 2 mm – 1 cm -MM over Breslow 2 mm – 2 cm lExcision and sentinel lymph node extraction -Breslow over 1 mm -Breslow 0.8 mm and ulcerations Adjuvant therapy lChemotherapy (Dacarbazine, Cisplatina) lInterferon (Intron, Roferon) lCryosurgery (skin metastasis) lRadiotherapy lTargeted therapy (BRAF, MEK inhibítory) lImunotherapy (check point inhibition) lCombination anti CTLA-4 + anti PD-1 lTherapy till progression or toxicity