Melanoma

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Slide 1 : Melanoma Edward Buckingham, M.D. Combined Plastics Conference September 6, 2000
Slide 2 : 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
Slide 3 : 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
Slide 4 : 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
Slide 5 : 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
Slide 6 : Evolution of Nevi
Slide 7 : Melanocyte Hyperplasia
Slide 8 : Junctional Nevi
Slide 9 : Compound Nevi
Slide 10 : Dermal Nevi
Slide 11 : 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
Slide 12 : 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
Slide 13 : Evolution of Melanoma
Slide 14 : 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
Slide 15 : Dysplastic Nevi
Slide 16 : Dysplastic Nevi
Slide 17 : Types of Melanoma Acral lentiginous Mucosal melanoma Superfical spreading melanoma Lentigo maligna melanoma Nodular melanoma
Slide 18 : 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
Slide 19 : Superficial spreading
Slide 20 : 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
Slide 21 : Lentigo maligna
Slide 22 : 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
Slide 23 : Nodular melanoma
Slide 24 : 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
Slide 25 : 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)
Slide 26 : Clinical early, increase in size, change in shape or color of pigmented lesion most common symptom pruritis late, tenderness, bleeding, ulceration ABCDE’s (asymmetry, border, color, diameter, elevation, surrounding tissue) Epiluminescence microscopy (ELM)
Slide 27 : 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
Slide 28 : 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
Slide 29 : Prognosis Breslow (thickness in millimeters) strongest predictor
Slide 30 : Prognosis Clark level less predictive, thin skin useful
Slide 31 : 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
Slide 32 : 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
Slide 33 : Work-up FDG-PET some use in distant disease sensitivity 17% in study with SLN biopsy
Slide 34 : 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
Slide 35 : Staging-Breslow <0.76 mm - thin 0.76 - 1.49 - intermediate 1.50 - 4.00 - intermediate >4.00 mm - thick
Slide 36 : Staging CS/PS (I, II, III) AJCC- Stage I and II - local, III - regional IV - distant
Slide 37 : AJCC Staging
Slide 38 : Surgical Treatment Recommended margins vary Rule of thumb <1mm then 1 cm 1-4mm then 2 cm >4mm then 3 cm All depths to underlying muscle fascia
Slide 39 : Nodal Disease CS-II remove regional lymphatics depending on location of primary and presence of distant metastasis
Slide 40 : 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 (<0.76) and thick (>4.0) no change with ELND
Slide 41 : Balch Study
Slide 42 : 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
Slide 43 : 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
Slide 44 : 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% Balch’s non-randomized study
Slide 45 : The Debate - CON ELND randomized trials 70% no occult disease sequential dissemination only theory
Slide 46 : Balch’s 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
Slide 47 : Sentinel Node Theory Essence of debate to identify those with occult metastasis Morton- first node in group to receive flow from tumor site
Slide 48 : 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
Slide 49 : 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
Slide 50 : 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
Slide 51 : 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
Slide 52 : 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
Slide 53 : 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

 


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