03-07 Melanoma

Question 1

• Likelihood of developing melanoma in one’s lifetime?
• men v. women
• blacks? hispanics?

Answer 1

Males: 1 in 37
Females: 1 in 56

0. 5% (1 in 200) for Hispanics
1. 1% (1 in 1,000) for blacks

Melanoma is the most common form of cancer for young adults 25-29 years old and the second most common form of cancer for young people 15-29 years old

Question 2

% caused by UV?

Answer 2

86% attributable to UV damage

Question 3

5-year survival rate?

Answer 3

• detected early, before the tumor has spread to regional lymph nodes or other organs, is about 98 percent in the US
• reached LNs: falls to 62 percent when the disease reaches the lymph nodes
• distant organ mets: Only 15%

Question 4

Where do melanocytes arise from embryologically speaking?

Answer 4

Neural crest cells

• explains how you can get non-skin melanoma (Amelanotic melanoma)

Question 5

Categories of Melanoma Risks

Answer 5

• Your UV exposure
• Your skin tone
• Nevi (moles)
• Genetic predisposition
• syndromes
• Immunosuppression
  
  • e.g. transplant pts

Question 6

Phenotypic risk factors for melanoma?

Answer 6

• Fair Skin
• Light hair/eyes
• More than 50 nevi
  
  • Atypical/dysplastic nevi
• Lots of freckles
• History of sunburn
• 1 sunburn damages a lot of DNA

Question 7

Genetic Risk Factors for Melanoma

Answer 7

CDKN2A mutation is most significant

• Codes p16/p14arf
• Cell cycle regulators
• Associated with 25-60% if familial melanomas

Family history of melanoma

Syndromes

• Xerodermapigmentosum

Question 8

Nevi-associated risks

Answer 8

• Large congenital nevi >20cm
  
  • Risk lifetime: 5-20%
• Numerous atypical nev
• >50 benign melanocytic nevi > 5mm

25-50% of melanoma arise in pre-existing

• However, this means that > 50% arise in normal skin (i.e. had no mole precursor)

Question 9

UV Exposure Risks

Answer 9

Sunburn

• Intermittent sunburns in unacclimatized fair skin (acute, intermittent exposure, e.g. weekend warriors)
• One or more blistering sunburns in childhood or adolescence more than double a person’s chances of developing melanoma later
• A person’s risk for melanoma doubles if he or she has had more than five sunburns at any age

Tanning salon use

• Just one indoor tanning session increases risk of melanoma by 20 percent

Treatment with UVA/Psoralen

• a tx for psoriasis

Question 10

With which patterns can melanoma present?

Answer 10

EARLY MELANOMA

1. Lentigo Maligna
2. Melanoma in Situ

PRIMARY CUTANEOUS MELANOMAS

1. Superficial Spreading Melanoma (SSM) 70%
2. Nodular Melanoma (NM) 15%
3. Lentigo Maligna Melanoma (LMM) up to 15% of melanomas
4. Acral Lentiginous Melanoma (ALM)
   
   1. 5-10% in Caucasians, up to 70% of melanomas in darkly complected individuals

Question 11

Dx?

• How deep?
• Early or late presentation?

Answer 11

Lentigo Maligna (LM)

• Confined to epidermis
• Sun exposed skin
• Ill-defined
• Not lentigo maligna melanoma

Question 12

Dx?

• Early or late presentation?
• How deep?

Answer 12

Melanoma in situ

• Confined to epidermis
• Sun or non-exposed skin
  
  • vs. only sun-exposed w/ LM
• More well defined than LM

Question 13

Dx?

• Early or late presentation?
• Typical presentation
  
  • Age?
  • Location by sex?

Answer 13

Superficial Spreading

• Middle time-course presentation
• Most common – 70%
• 30-50 year olds
• Men – trunk
• Women –back of legs

Question 14

Dx?

• Age of presentation
• typical place on body it presents

Answer 14

Nodular Melanoma

• 2nd most common – 15%
• Age: 60 year olds
• Trunk, head and neck

Question 15

Dx?

• How common
• Age?
• Skin areas?

Answer 15

Lentigo Maligna Melanoma

• Up to 15%
• Age: 70’s
• Sun damaged skin

Question 16

Dx?

• Presents in what population?
• How common?
• Age?

Answer 16

Acral Lentiginous

• 5-10% light skin, 70% in darker skin
• Age: 50-60’s
• Hands and feet - digits

Question 17

Dx?

• How common?
• DDx

Answer 17

Amelanotic melanoma

• ~2% of melanomas
• Clinically can appear similar to BCC
  
  • Can’t tell by looking
  • Non pigmented = red color
  • Or can look like this:

Question 18

Name non-sun exposed areas to check for meloma

Answer 18

• Periungual - around the nail or under the nail
• Mucosal ~5%
  
  • Genital
    
    • 4.7% whites
    • 12%Hisp
    • 2% blacks
  • Oral 1.9%
  • Anorectal .3%, urethra .2%,
• esophagus 0.1%
• Ocular ~5 %
• “Melanoma of unknown primary” – metastatic melanoma presents internally, but no original source from the skin is known.

Question 19

Pediatric Melanoma

• Usually presents where?
• Prognosis?
• Most common subtype?
• Most common in which age range of pedi pts?

Answer 19

• head and neck
• prognosis: Mortality before age of 10 is rare
• superficial is most common subtype
• kids w/ cogenital melanocytic nevi (CMN) are >400X more likely to get melanoma
• Most commonly in pedi-patients aged 10-19
• Melanoma accounts for up to three percent of all pediatric cancers
• Diagnosis and treatment is delayed in up to 40 percent of childhood melanoma cases.

Question 20

ABC’s of Melanoma + Other suspicious findings

Answer 20

• A - Asymmetry
• B - Border
  
  • -Jagged
  • -Blurred
  • -Irregular
  • -Notched
  • -Missing
• C - Color varies over surface
• D - Diameter ≥ 6 mm (pencil eraser)
• E - Evolution
  
  • i.e. mole changes in
    
    • ABCDs

Other Suspicious Findings

• Inflammation within or around the nevus
• “Ugly duckling”
  
  • diff than pt’s other moles
• Bleeding or scabbing w/o trauma

Question 21

Melanoma is most commonly found in:

• ____ on men
• ____ on women

Answer 21

• Men: Trunk (his lecture) back (AAD learning module)
• Women: legs

Question 22

Prognostic Factors (7)

Answer 22

• Men do worse
  
  • ?b/c they present later
• Site - % survival – best to worst:
  
  • extremities >
  • head, neck, trunk, >
  • volar (palm/sole) or sublingual
• Ulceration = worse
• Deeper (Breslow depth) = worse
• LN
  
  • more, and more palpable LN involvement = worse
  • visceral worse than non
• Age- older age = worse prognosis
• Mitoses – > 1 = worse

Question 23

What does the “T” in TMN Staging stand for when talking about melanoma?

• Importance of this value?

Answer 23

T = thickness

• highly correlated w/ prognosis
• resection margins are based on it

Question 24

• Stages (roughly)
• Treatment of melanoma by stage?

Answer 24

See attached picture for stages

• Stage 1-2a - excision only
• Stage 2b-2c - exicision + interferon
• Stage 3 - WLE (wide local excision)
  
  • clinical trial +/-
  • interferon-alpha +/-
  • observation
• Stage 4 - rapidly changing
  
  • Ipilimumab
  • Vemurafenib
  • Clinical trials
  • High dose IL-2

Question 25

Ipilimumab

• MoA
• Efficacy
• Side Effects

Answer 25

• MoA blocks CTLA-4 inhibitory signal to CTLs allowing CTL stimulation which kill cancer cells (see picture)
  
  • Idea is that the cancer cell is inhibiting immune response
• Efficacy:
  
  • Average survival increase ~2months
  • Takes months to get response
  • Only 20% of pts respond
• ADRs:
  
  • auto-immunity (b/c you are revving up the immune system)
  • Diarrhea most common (can be additive with IL-2)

Question 26

Vemurafenib

• MoA
• Efficacy
• Side Effects

Answer 26

MoA

• Binds and inhibits mutant form (V600e) of BRAF which is in Ras cell proliferation signal cascade
  
  • 45% of metastatic melanoma tumors have a BRAF activating mutation
  • Need to test for this first
  • Approved for metastatic or unresectable MM

Efficacy

• 20% survival increase at 6 months
• ~50% response rate
• effects seen in days to weeks but duration of response only 5-6 months

Side Effects

• Many skin side effects
• SCC eruptions (18%) (B/c of inhib of BRAF)
• Other cancers
• Photosensitivity (12%)

Question 27

What does SPF actually mean?

Answer 27

SPF

• Measures blockage of UVB only
• SPF XX – skin takes XX times as long to burn (redden) after proper application
• Real world use is about ½ of SPF on the bottle
  
  • The test w/ 2mg/cm2
• Higher numbers may last longer

UVA

• When a bottle says “UVA coverage” this is not included in the SPF.
• No qualitative measure for UVA