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Skin Cancer

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Skin Cancer

  1. 1. SkinCancer W3 L1 & 5 Skin Cancer Malignant Melanoma - Nowthe most commoncancer in15-24 yearolds - Twice as manyyoungwomengetmelanomabutmore mendie - FastestincreasingcancerinScotland. More commonin females(2:1) - Ugly ducklingsign –one mole outof manyis differentcolourandshape - Can arise at any site butmostcommon onsun exposedsites –scalp,face,neck,arm, trunk,leg - Rarelyoccur ineye,meninges,oesophagus,biliarytract,anus– cellsgettrappedin embryogenesis BreslowThickness – the depthfromthe granularlayerof the epidermistothe deepestmelanoma cell.Itis usedasa prognosticindicatorof skincancer. - BreslowThickness < 1 mm 5 yearsurvival is95-100% - BreslowThickness 1-2mm 80% - BreslowThickness > 4 mm 50% - Metastases 5% - Thinmelanomasare cured.Earlydiagnosisisessential. A – asymmetry B – border C – colour– lightbrownisacceptable,anyothercolourisnot (pinkblue andwhite are the worst colours).Irregularpigmentation. D – diameter– upto 6mm isok E – evolution –change?Pain?Bleeding?Oozing? Satellite nodules?Ulceration? Otheradverse prognosticindicators • Ulcerationisa strong adverse indicator • Suffix bindicatestumourulceratione.g.pT3bisa tumourbetween2-4mmwithulceration – ulcerationjumpsupa stage and survival rate decreases. a = notulcerated(e.g.pT1a) • Highmitoticrate,lymphovascularinvasion,satellites,sentinellymphnode involvement • Satellite depositsof melanomainskin=advancedmetastatic disease –verydifficulttomanage, palliativecare Four maintypesof melanoma: • Superficial spreading (SSM) –trunksof menand legsof womenare the most commonareas. Most commonsubtype,affectsyoung/middleagedadults. Usuallymaculewithirregularborder and colourwhichmayhave beenincreasinginsize foryears(slow horizontal growthphase) before developinganodule (rapidvertical growthphase). • Acral/mucosal lentiginous-acral andmucosal (A/MLM) – palms,soles,nails andmucosal sites. Usually inelderlypatients.Hutchinsonsign –pigmentedextensionintothe nail fold • Lentigomaligna-sun-damagedface/neck/scalp (LMM) – elderlyface usually.Neoplastic melanocytesalongthe basal layerwhichmaythenbecome invasive • Nodular- variedsitesbutoftentrunk • Notmain subtype - Amelanocyticmelanoma–Absentorminimal visible pigment.Rare.
  2. 2. SkinCancer W3 L1 & 5 SSM, A/MLM and LMM: - Grow as maculeswheneitherin-ituorwithdermal microinvasion(radialgrowthphase) - Eventuallythe melanomacellsinvade the dermisforminganexpansile masswithmitoses (vertical growthphase) - Onlymelanomaswithavertical growthphase canmetastasise Nodularmelanoma: - No clinical ormicroscopicevidence of RGP - A nodule of VGPtumour - Some considerthismore aggressive - Occurs at any bodysite - Usuallyinolderpatients - Blue-blackorred-skin-colourednodule whichmaybe ulceratedorbleedingandhasusually developedrapidlyoverprecedingmonths - Unlike nodulesdevelopinginsuperficial spreadingmelanoma,nodularmelanomasdonot have any significantsurroundingmacularpigmentation MM spread - Local dermal lymphatics satellite depositsof MM – verybad prognosticsign - Regional lymphnode metastases –commonpatternof disease progression. Nodesexcised (radical lymphadenectomy) - Bloodspread - Skin/ softtissue,Heart, Lungs,GI tract, liver,brain MM treatment: • Primaryexcisiontogive clearmargins • Narrowcomplete excisionforconfirmationof diagnosisandassessmentof Breslow • If in-situthenclearbycirca 5mm • If invasive but<1mm thick -1cm clearance • If invasive and>1mm thick -2cm clearance • SNB if >1mm thickor thinnerwithmitoses • Some alsoreceive asentinel nodebiopsy • Sentinel lymphnode biopsycanprovide furtherprognosticinformation. If SN positive- regional lymphadenectomy • Treatmentof advanceddisease difficult • Chemo,immunotherapy,genetictherapies Melanomagenetics Some acral melanomashave c-kitmutationsandmaybe treatedwithimantinib Melanomasonintermittentlysun-exposedskinmayhave BRAFmutation - Wildtype BRAFis a weakcytosolicproto-oncogene - If mutateddrivescell proliferationbyup-regulatingMEKand ERK - Range of drugsdevelopedtointerferewiththispathwaye.g.dabrafenibandvemurafenib - Response timesare limited(onlyworksforabout6 months) - May be betterincombinationwithMEKinhibitor - May be betterinadjuvantsettingforhighrisklesionsbefore metastasesdevelop - Rapidlyevolvingarea
  3. 3. SkinCancer W3 L1 & 5 Non-melanoma skin cancer – Basal cell and squamous cell • 90-95% of skincancers & Commonesthumancancer • >100,000 cases peryearin UK & ~500 deaths/year Basal Cell Carcinoma (BCC) Clinical Presentation - ~ 75% of NMSCs;verycommon – increasinglyseenin youngerpatients - Basal cellssproutfromepidermisandgroupsof cells invade/budintodermis - Mitosesandapoptosisverynumerous - slowgrowinglumpornon-healingulcer–nodular, superficial or ulcerated/infiltrative BCC - painlessandoftenignored - ‘pearly’ortranslucentbutcan be pigmentedBCC - visible,arborisingbloodvessels - central ulceration - “rodentulcer” - can presentasscaly plaque - ‘superficial BCC’ - can be infiltrative- ‘morphoeicBCC’ – tumourcellsdosubclinical therefore are hardtotreat - locallyinvasive,butrarelymetastasize40 yrs,but can be 3rd or 4th decade - Margins are poorlydefinedandmayspreadalongnerves - Can damage bonesof face or eyesif too close – resectionischallenging - May kill byinvadingeye  brain–veryhard to treat/cure Squamous Cell Carcinoma Clinical Presentation - about20% of all skincancers - hyperkeratotic(crusted) orwarty lumpor non- healingulcer - arisesonsun-damagedskin - grow relativelyfast,maybe painful &/orbleed – feel lumptodiagnose - majority- well differentiatedlowriskSCC –best prognosis - minority - poorlydifferentiatedhighriskSCC – worstprognosis - Ear, face,lipand scalpare highrisksites - Perineural spreadisanadverse prognostic indicator - Precursors:Bowen’sdisease (esp.onlegs), Actinickeratosis(esp.onhead/neck),Viral lesions(esp.onanogenitalskin).These precursorsshow squamousdysplasia - NotuncommoninUK forSCC to grow onchronic ulcers/scars/wounds - Rare associationswith xerodermapigmentosumanddystrophicvariantepidermolysisbullosa
  4. 4. SkinCancer W3 L1 & 5 - riskof metastasisabout5% - seriousconsequences - poor prognosisonce metastatic - Keratoacanthoma(KA) - self-resolving(notmalignantbutlookslikeSCC – remove tobe sure) - 50% furtherNMSCat 5 years - 5 yearsurvival rate of metastaticSCC25% Actinickeratoses–pre-cancerousskinlesions,highlyassociatedwithincreasedriskof SCCor BCC. Oftenmultiplegiving“fielddamage”ormore severe “fieldcancerisation”. Potentially pre-malignant cutaneous tumours: Actinickeratosis: - Developlaterinlife inwhite-skinnedpeoplewhohave hadsignificantsunexposure - Appearonsun exposedareas - Erythematoussilver-scalypapulesorpatcheswithaconical surface and redbase - Backgroundskin isofteninelastic,wrinkledandmayshow flatbrownmacules(solar lentigos) reflectingdiffuse solardamage - Small proportioncantransforminSCC but onlyaftermanyyears - Tx – cryotherapy,topical 5-fluoroacill cream, 5% imiquimodcreamordiclofenacgel Bowen’sdisease - Intraepidermalcarcinomain-situ - Rarelybecomesinvasive - Due to longterm sunexposure andpresentsonsunexposedareas,mostcommonly womenslegs - No maturationof cellsleadstoparakeratosisonsurface - Isolatedscalyredpatchor plaque lookinglike psoriasisbutithas an irregularedge - Slowlyincrease withtimebutnodermal invasion - Tx – cryotherapy,topical 5-fluoroacill cream, 5% imiquimodcream, cryotherapy,curettage Actinickeratosis - Verycommon - Sun-exposedskinesp.scalp,face,hands - Variable epidermal dysplasia - Severelyatypical lesionsare bowenoid(lookslike bowensdisease) - Commonprecursorof invasive SCC Atypical/Dysplasticnaevussyndrome –see W3 L3&4 notes Giant congenital melanocyticnaevi - see W3L3&4 notes Viral precursors - Viral genital lesionsoftendysplastic withelevatedatypical mitoses - Erythroplasiaof Queryat= penile Bowen’s - AssociatedwithHumanpapillomavirus - HPVtype 16 associatedwithdysplasia - HPV in almost100% penile dysplasia.HPV foundin50% invasive penileSCC
  5. 5. SkinCancer W3 L1 & 5 Risk factors for skin cancer - Sunexposure (espUVA) o Sunburnandsolar lentigo(liverspots,oldage spots) reflectUVBdamage,whereassolarageing isattributedtothe deeperpenetrationandsolar elastosisof UVA. o The formationof ‘sunburn’cellsisaprotective mechanismwherebybadlyUV-damaged keratinocytesundergoapoptosisorprogrammedcell death.Frecklesoccurinthose who cannot tan sufficientlytoprotecttheirskinfromsun. o Damage occurs repeatedlyleadingtoDNA mutationsandskincanceroccurs o Up to 80% sun damage occurs duringfirst18 years o Childhoodsunburnincreasesmelanomarisk4x o SCC - chronic,cumulative UV-exposure(total exposureisthe mostimportantfactor, irrespectiveof howitisachieved) o BCC - intermittent,intensesunburnepisodes o Melanoma- intermittent,intensesunburnepisodes o Those whowork outdoors(farmers,sailorsetc) are at increasedriskastheyare constantly exposingtheirbodiestothe sun. - Geneticsusceptibility o Amountandtype of melanindictatesyouskintype (SPT1-4) o DNA repairsyndromes,e.g.XerodermaPigmentosum –defectinone of 7 nucleotide excisionrepairgenesleadingtophotosensitivity,skincancersonUV-exposedsites, neurological degenerationandincreasedriskof othercancers o Albinism o Naevoidbasal cell carcinoma(Gorlin’s) syndrome –autosomadominantfamilial cancer syndrome – earlyonset/multiple BCCs.Palmerpitsjaw cystsandectopiccalcificationfalx - Immunosuppression –SCC isthe most commonformof skincancerin these patients.Organ transplantrecipientsneedregularskinsurveillance. - Otherenvironmental carcinogens:coal tar,smoking,ionisingradiation,arsenic,trauma,chronic ulceration Phototoxic drugs: - Voriconazole Thiazide diuretics - Anti-TNF NSAIDs - BRAFinhibitors Skin cancer prevention Behaviour: - avoidsunat its height(11am-3pm) - use shade whereverpossible - particularcare of babies/children avoidsunbeds Sunscreens- broadspectrum(SPF25+) withUVA protection Clothing - tightlywoven,loose fittingclothing (dark) - longsleeves,trousers,skirts Regular (self-) surveillance Examine molesregularlyandif in doubt“check itout” Sun Smart S – Stay inthe shade 11am-3pm M – Make sure youneverburn A – Alwayscoverup R – Remembertotake extracare with children T – Thenuse factor 15+ sunscreen
  6. 6. SkinCancer W3 L1 & 5

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