黑色素瘤47699

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Melanoma,Edward Buckingham, M.D.,Combined Plastics Conference,September 6, 2000,1,Melanoma - Outline,General statistics and development,Risk factors and patient assessement,Pathology and prognosis,Work-up and staging,Surgical treatment,Lymph node controversy/sentinel node,Adjuvant therapy,2,Melanoma - Data,Incidence increase fastest,Mortality increase 2nd only to lung,5th most prevalent, incidence 7%/year increase,5% skin cancer, 75% skin cancer death,1/75 in 2000, 1/1500 in 1935,20% H&N, 51% facial, 26% scalp, 16% neck, 9% ear,3,Development of Nevi,Melanocytes,dendritic, neural crest, basal cell layer,synthesis of melanin,1/10 to keratinocytes,hyperplasia- tanning/lentigines, increased ratio,Nevus transformation,poorly understood,dendritic- rounded,no longer lentigionous pattern- nests,4,Development of Nevi,Junctional nevi,nests along dermal-epidermal junction,Compound nevi,“invade” dermis, first as nests then cords and single cells,Dermal nevi,junctional component lost,5,Evolution of Nevi,6,Melanocyte Hyperplasia,7,Junctional Nevi,8,Compound Nevi,9,Dermal Nevi,10,Developement of Melanoma,Questionable,benign melanocytes,progressive hyperplasia/dysplasia,Radial growth,in epidermis, lines of radii, no expansive nests or nodules,slow unrestricted , no metastatic potential,11,Development of Melanoma,Vertical growth,vertically into dermis,expansive and coalescent nests and nodules,metastatic potential dermal lymphatic and vascular invasion,Growth patterns,biphasic- slow radial months to years- rapid vertical growth,monophasic- rapid vertical growth only,12,Evolution of Melanoma,13,Dysplastic Nevi,border melanocytic nevi and malignant melanoma,clinical resembles malignant melanoma,lentiginous compound nevus, prominent bridging across rete ridges,aberrant in inter-rete spaces,lamellar fibrosis of papillary dermis, variable lymphoid response,14,Dysplastic Nevi,15,Dysplastic Nevi,16,Types of Melanoma,Acral lentiginous,Mucosal melanoma,Superfical spreading melanoma,Lentigo maligna melanoma,Nodular melanoma,17,Superficial spreading,most common head and neck, 50%,4th to 5th decade,clinical mixture of brown/tan, pink/white irregular borders, biphasic growth,irregular nests in epidermis,underlying lymphoid infiltrate,enlarged nests and single cells in all epidermal layers,18,Superficial spreading,19,Lentigo maligna,20% of head and neck,longest radial growth phase 15 yrs,elderly sun exposed areas,clinical dark, irregular ink spot,contiguous lintiginous proliferation, dyshesive, variable shape, atrophic epidermis, infundibular basal cell layer of hair follicles,20,Lentigo maligna,21,Nodular melanoma,30% of head and neck,5th decade,aggressive monophasic growth,sun-exposed and nonexposed areas,well circumscribed blue/black or nodular with involution in irregular plaque,downward tumorigenic growth, expand papillary dermis into reticular dermis,22,Nodular melanoma,23,Mucosal melanoma,8% head and neck,histologic staging little use,local control predicts survival,neck dissection for clinical N+,XRT for histo N+,adjuvant interferon alpha 2-b,24,Risk factors,Type I or II skin,atypical and congenital nevi,actinic skin changes,history of melanoma,family history of melanoma, atypical nevi,history of significant sun exposure (blistering),25,Clinical,early, increase in size, change in shape or color of pigmented lesion,most common symptom pruritis,late, tenderness, bleeding, ulceration,ABCDEs (asymmetry, border, color, diameter, elevation, surrounding tissue),Epiluminescence microscopy (ELM),26,Biopsy,excisional biopsy or saucerization if small,incisional if large,Depth of biopsy must be to sub-Q fat,if melanoma a second excision must be performed,27,Pathology,diagnosis, tumor thickness in millimeters, margins,histologic subtype, anatomic site, Clark level, mitotic rate, growth phase, ulceration, regression, lymphocytes, angiolymphatic spread, neurotropism, microsatellitosis, precursor lesion,28,Prognosis,Breslow (thickness in millimeters) strongest predictor,29,Prognosis,Clark level less predictive, thin skin useful,30,Prognosis,anatomic site, ulceration, gender, histologic type, nodal disease,head and neck- scalp worse,extremity better trunk,women better men,lymph node +,Breslow thickness, ulceration, # pos. nodes,Cohen 10 yr survival # nodes positive,31,Work-up,H&P,entire skin, inguinal, axillary, supraclavicular, H&N nodes,especially primary drainage,brain, bone, GI, constitutional symptoms,palpable nodes FNA,Labs and imaging,vary, CXR to routine CT chest and LFT,H&N CT neck routine,If stage III(regional) or IV (distant) - CT head, chest, abdomen, pelvis,32,Work-up,FDG-PET,some use in distant disease,sensitivity 17% in study with SLN biopsy,33,Staging-Clark,Level I - in situ at basement membrane,Level II - through basement membrane into papillary dermis,Level III - spread to papillary/reticular interface,Level IV - spread to reticular dermis,Level V - sub-Q invasion,34,Staging-Breslow,4.00 mm - thick,35,Staging,CS/PS (I, II, III),AJCC- Stage I and II - local, III - regional IV - distant,36,AJCC Staging,37,Surgical Treatment,Recommended margins vary,Rule of thumb,4mm then 3 cm,All depths to underlying muscle fascia,38,Nodal Disease,CS-II remove regional lymphatics depending on location of primary and presence of distant metastasis,39,CSI- The Debate,Balch study- nonrandomized,5 and 10 yr survival intermediate thickness (0.76-3.99) doubled with ELND,5 and 10 yr survival for thin (4.0) no change with ELND,40,Balch Study,41,CSI - The Debate,Four prospective randomized trials,Mayo clinic 3 groups stage I (ELND, delayed, none) no survival difference, increased complications if none, criticized not looking at subgroups to benefit,WHO no survival benefit, criticized no subgroups, largely extremity lesions in females,42,CSI - The Debate,Four prospective randomized trials,Balch - no overall 5 yr difference, improved in patients , 60 yrs with ELND, 1-2 mm tumors, no ulceration, or both benefited,WHO trunk 1.5 mm or more immediate or delayed no significant survival benefit, however was between ELND with occult metastasis and later developers with delayed LND,43,The Debate - PRO ELND,sequential dissemination theory,30% stage I & II occult disease,Once palpable 70-80% distant disease, 10 yr survival 15-25%, 5 yr 1-2 nodes micrometastasis 65%,Balchs non-randomized study,44,The Debate - CON ELND,randomized trials,70% no occult disease,sequential dissemination only theory,45,Balchs recommendations,Three groups,local, local plus micro, local plus distant,Thin - 95% cure rate no benefit to ELND,Intermediate - 60% regional, 20% distant, benefit ELND,Thick - 60% regional, 70% distant, no benefit,Should consider other factors as well,46,Sentinel Node Theory,Essence of debate to identify those with occult metastasis,Morton- first node in group to receive flow from tumor site,47,SLN - procedure,isosulfan blue injection at tumor site, follow channels to node,studies with ELND 80% sensitivity, specificity 99%,preoperative lymphscintigraphy, intra-operative radiolymphoscintigrapy, and isosulfan blue dye,69.5% SLN excised blue dye, 83.5% “hot”, combined success 96%, location matters,48,SLN - Utility,prognostic indicator - study SLN status most significant indicator of disease-free and disease-specific survival,pathology,H&E, S-100, HMB-45 limited by # sections,reverse transcription with polymerase chain reaction (RT-PCR)- peripheral blood and nodes, (mRNA tyrosinase) 29 ELND 38% path positive, 66% RT-PCR positive,49,Adjuvant Therapy,Radiation,high dose (400-500 cGy) bulky, residual, recurrent, unresectable, ill,lentigo maligna 5 yr cure 80% (disfiguring, debilitating location),adjuvant- trend toward improved regional control in N+ dissected necks,palliate - especially bony mets,50,Adjuvant Therapy,Chemotherapy,response 25%, durable control 1%,consider in CSI with 1.5 mm, CSII with WLE, TND,no survival advantage demonstrated,single agent dacarbazine (DTIC),multiple combinations carmustine, cisplatin, DTIC, tamoxifen,51,Adjuvant Therapy,Immunotherapy,unusual behavior, no survival benefit,Interferon,ECOG 1684, 4mm or N+, 6.9 yrs high dose IFN-alpha-2b, improved disease-free and overall survival approx. 1 yr. 26% dropout rate toxicity,52,Summary,Incidence and deaths on rise,Survival rates increasing due to detection and thorough treatment,Depth and nodal status most important prognostic indicators,ELND still debated,SLD useful,Other modalities therapy further research,53,