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:
Familial: 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
- Goals
- 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
- IL2
- 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
- Zelboraf: vemurafanib: inhibitory molecule selective for V600E mutation
- 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
- Adjuvant for high risk melanoma: significantly prolongs relapse free survival, 26% risk reduction
- 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
- Increasing in incidence
- 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
- MC benign skin tumor
- 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
- Basics
- 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