Skin Cancer: Melanoma, BCC, SCC, etc

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Skin Cancer

  • Skin Cancer:
    • 40% of all cancer cases
    • >1 million cases/yr
    • 40-50% US population affected
    • 95% curable
    • Geographic risk: highest rates of UV radiation: South Africa and Australia; In US Florida and Texas
  • Melanoma
    • Increasing in incidence
      • US: inc from 1:1500 (1935) to 1:74 (today)
    • Risk factors:
      • IMG_6695Familial: skin type and color; h/o malignant melanoma
        • White men highest risk
      •  Environmental
        • >3 blistering sunburns before age 20
        • Outdoor jobs >3 years in adolescent years
        • Use of sunlamps and tanning beds
      • Other
        • Actinic keratosis, elastosis
        • Marked freckling on upper back
        • Large number of normal nevi
        • Atypical nevi, congenital giant nevi
    •  Characteristics
      • Asymmetrical: one half the lesion is shaped differently
      • Border: irregular, blurred or ragged
      • Color: inconsistent pigmentation with varying shades of black or brown
      • Diameter: >6mm or a progressive change in size
      • Evolution: history of change of lesion
    • Types
      • Superficial Spreading (60%): prolonged radial growth phase, notching scalloping, areas of regression
      • Nodular: (15%): darker and thicker than superficial spreading, rapid onset; commonly blue-black or blue-red (5% amelanotic)
      • Lentigo Maligna (%5) enlarge slowly, usually large, flat, tan or brown
      • Acral Lentiginous: (rare: Asians 46%, blacks 70%) on soles, palms, subungual, usually large, tan or brown, irregular borders. Anti-reggae.
      • Desmoplastic (1.7%) rare locally aggressive, occur primarily on neck and head in elderly
    • Dx
      • <1.5cm : excisional biopsy
      • >1.5cm: Incisional Biopsy
      • Punch biopsy OK: look at ‘worst’ part
        • Goals
          • Narrow excisional bx: 2-3mm
          • Rule out lesions with potentially similar features:
            • seborrheic keratosis
            • pigmented basal cell ca
            • solar lentigines
            • atypical nevi
          • Determine depth of invasion
          • Identify prognostic features of the primary: ulceration and regression
      • Tests: get LDH (terrible prognosis, upstages), LFT
    • Staging: Breslow
      • T1            0-.75mm              Thin
      • T2            .75-1.49mm        Intermed
      • T3a         1.5-3.0mm           Intermed
      • T3b         3.01-4mm            Intermed
      • T4            >4mm                  Thick
    • Prognostic factors:
      • MULD: Mitotic rate, Ulceration, LDH, Depth of invasion
      • Male sex
      • Trunk/head and neck
      • Age:
        • Mortality increases with increasing age
        • Lymph node metastases higher in younger patients
      • Nodular sub-type
      • High mitotic rate (>6 mm2)
    • Recommended margins
      • Melanoma in Situ: 5mm
      • <1mm = 1cm
      • 1-2mm = 1-2cm
      • >2mm = 2 cm
      • May be modiefied by anatomic considerations
      • Negative peripheral margins important in ill defined lentigo maligna lesions
      • On the digits: Amputation at least one joint proximal to the tumor and sentinel node bx
    • Risk of nodal disease
      • <1mm w/o ulceration <5%
      • 1-4mm = 20%
      • >4mm = 35%
    • Sentinel Lymph Node Bx:
      • Radiocolloid and vital blue dye (given intradermal) improve accuracy
      • Excision of primary should occur at time of SLNB
      • Can be performed after: no decrement in identifying SLN after previous wide excision
      • Indications:  >1mm, any ulcerated, >1 mitosis/mm2
        • All pt with invasive melanoma
        • Primary melanoma >1 mm
        • M75 with ulceration, deep invasion, regression, truncal location, and mitoses
        • Pt with nevomelanocytic lesions assessed by bx in which biology is uncertain
      • If positive: 2.2x risk of recurrence and deaths
    • Lymphadenectomy
      • Deep inguinal lymph node dissection for: > 4 positive lymph nodes on superficial dissection, positive Cloques node (subinguinal), enlarged ileo-obturator lymph nodes on CT, clinically palpable or extracapsular invasion of femoral lymph nodes
      • A/E: 30% have lymphedema, wound complications, or other a/e
    • MSLT2 trial: positive node: dissection or u/s obs
    • 5 year survival: depth, with and w/o ulceration
      • <1mm   95%       91%
      • 1-2mm 89%       77%
      • 2-4mm 78%       63%
      • >4mm   67%       45%
    • Adjuvant Therapy: chemo, biochemo, immune, braf inhibitor
      • Adjuvant for high risk melanoma: significantly prolongs relapse free survival, 26% risk reduction
        • 15% overall survival improvement, 1 year benefit
        • stage 4 (6-9mo median survival, 5 year 6%)
      •  Indication: Pt high risk for systemic dz
        • Ulcerated
        • Positive LN
          • In transit tumor cells
        • Thick primary >4mm
        • Regional Recurrence
      • Chemo
        • Dacarbazine: response 20%, no change in survival
        • Temozalmide: oral agent, crosses bbbb, no change in survival
        • Combo: Cisplatin, vinblastine, dacarbazine
          • Improved response 25-30%, no change in survival
      • Immunotherapy:
        • IL2
          • T cell growth factor, produced by t cells
          • Induces T and NK cell proliferation
          • Strong anti tumor properties
          • Approved for melanoma and renal cell
        • INFalpha
          • IFN alpha 2b: for stage 3
          • Survival benefit 1 month
      • Targeted therapies:
        • Zelboraf: vemurafanib: inhibitory molecule selective for V600E mutation
          • BRAF: mutated: acquired to activate map kinase pathway
          • Selects out the 40-60% of melanoma with NRAF mutation
          • Response rate 48%, survival at 6 mo 84 v 64 with dacabazine as control
          • Unknown MOA: protein death 1
          • A/e cutaneous scc and keratoacanthoma
      • MAB:
        • Ipilimumab & nivolumab trial for metastatic tx/ 4 mo gain (10mo total)
        • Ipilimumab: CTL4 blocker: increases antitumor T cell survival
          • A/e: colitis, rash, elevated LFTs
          • Increased survival rates 21 v 12% v vaccine
    • Metastatic Melanoma
      • Considerations: Prior disease free interval, sites of dz, amount of tumor burden, ability to resect entire disease, pt performance, potential to down stage with systemic therapy
    • Mucosal melanoma: poor actors: locally excise
      • Unlikely to have braf mutation
    • Occular melanoma: go to liver even after enucleation
      • Ckit mutation: studying gleevec
  • Seborrhaic Keratosis
    • MC benign skin tumor
      • Ddx melanoma
    • Greasy/waxy stuck on raised appearance, oval
    • Clonal origin: neoplastic not hyperplastic
    • RF: sun exposure , age
      • Familial predisposition with postulated AD inheritance
    • MC location: face, neck, back
      • Never found on mucosa, palms or soles
      • “Never occur before 30”
    • Can spontaneous regress, assoc with pregnancy, inflammatory skin conditions and malignancy
    •  Tx: Ablative: cryotherapy, laser, electrodessication, surgical
  • Basal Cell
    • Basics
      • MC skin cancer 90%
      • Arise from lowest layer of the skin
      • Rarely metastasize or spread
      • RF: UV radiation: Sun exposed areas
        • Canthi of eye and nose
        • 86% on face
      • Failure to heal
      • Indolent
    • MC: modular type: face; waxy central cupping no ulceration
    • Superficial scaly plaque, sm compared to squamous cell 15% and truncal, no raised edges
    • Tx MOHs surgery: tangential/ transverse chemo fix and map and plan next cut: failure rate less than half other modalities; involve plastic surgeon; cold knife or radiate, can freeze, electodesicate;
      • If recurrence: more MOHs
    • mets very rare, occur only if neglected
      • no chemo no LN resections
      • Txlocal excision with clean margin’s
    • 2-3mm margin
  • Squamous cell
    • RF: UV: exposure, chronic inflam sites, long standing wounds: scar, burn, pilonidal, anal fistulae, xeroderma
    • Tx goal: complete removal: excision with narrow margin is acceptable
      • Curettage: dermatologist
      • Cryotherapy: liquid nitrogen
      • Mohs Surgery: Best for face, neck, hands
      • Radiation Therapy: inaccessible locations, recurrence
      • Topical Chemotherapy: fluorouracil
      • Surgical: 2-3mm margin
  • Merkel Cell Carcinoma
    • Cutaneous neuroendocrine tumor with keratin filaments and cytoplasmic dense core neuroendocrine granules
    • Oval shaped synaptic receptor cells
    • RF: UV, ICed, polyomavirus
      • Occurs in sun damaged skin and lymphatic spread is common
      • More common in immunosupporessed
    • tx wide excision 1-2cm margin with SNLBx and positive in most
    • Chemo: platinum
    • Rad: >2cm do radiation
    • Bad prognosis, high propensity for local recurrence
  •  Bowen
    • Carcinoma in situ of the skin
    • RF: sun exposure, chronic immunosuprresion, hpv
    • Tx: WLE
  • Spitz Nevi
    • Solitary benign melanotic proliferations
    • Children < 10 y/o
      • Pink/red and dome shaped
      • Pattern: starburst transitions to reticular
    • Adults: brown or black
      • Tx: Excision with 2mm margin

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