Malignant Melanoma Robert Miller MD www.aboutcancer.com
melanocyte melanoma epidermis dermis
Malignant Melanoma Accounting for about 3 to 4% of all
diagnosed skin cancers, melanoma begins in the melanocytes, cells
within the epidermis that give skin its color. The incidence is
rising by 3% a year.
Most Common Skin Cancers in 2013 Basal Cell : 2,800,000 (78%)
Squamous: 700,000 (20%) Melanoma: 76,690 (2%) Between 40 and 50
percent of Americans who live to age 65 will have either BCC or SCC
at least once, about 2% will get melanoma
Melanoma Gender Distribution - US Male Female
New Cases New Cases 43,890 (5%) 34,590 (4%) Death Death 6,470
3,240 2014 Data
Age Distribution 0.25 US (2000-2011) from the NCDB 0.2 0.15 0.1
0.05 0 20 30 40 50 60 Age Distribution 70 80 90
Lifetime risk of an American developing invasive melanoma
Probability (%) of Getting Melanoma (2008-2010) Age Men Women
0-49 50-59 60-69 70+ 0.4 0.4 0.8 2.1 0.5 0.3 0.4 0.9 Lifetime 2.9%
1.9%
30 Melanoma by Race 25 20 15 10 5 0 white hispanic asian black
SEER database from 2000 to 2004, the male incidence rates per
100,000
Risk Factors Freckling mild moderate severe
Risk Factors Sun (Solar) Skin Damage Severe solar damage
Risk Calculator for Melanoma
http://www.cancer.gov/melanomarisktool/
Appearance and location of melanoma
Distribution of superficial spreading melanoma
Distribution of Skin Melanomas Men on their back
Distribution of Skin Melanomas Women on the back legs
45 yo man with mole on his back for years presented with
headaches and was found to have widespread (brain, liver, lung, b
owel spread) liver biopsy showed metastatic melanoma
45 yo man with mole on his back for years presented with
headaches and was found to have widespread (brain, liver, lung, b
owel spread) liver biopsy showed metastatic melanoma
Possible signs and symptoms of melanoma A is for Asymmetry: One
half of a mole or birthmark does not match the other. B is for
Border: The edges are irregular, ragged, notched, or blurred. C is
for Color: The color is not the same all over and may include
shades of brown or black, or sometimes with patches of pink, red,
white, or blue. D is for Diameter: The spot is larger than 6
millimeters across (about inch the size of a pencil eraser),
although melanomas can sometimes be smaller than this. E is for
Evolving: The mole is changing in size, shape, or color.
Superficial Spreading Melanoma
Nodular Melanoma
Lentigo Maligna Melanoma
Variety of Melanoma Skin Lesions
Twenty images of skin lesions. Images 1-6, 7-13, and 14-20 show
atypical, benign, and malignant lesions, respectively.
Recurrent melanoma with subcutaneou s nodules
Stage Distribution Melanoma by Race, United States, 2003 to
2009. All White Black
Stage Distribution Melanoma by Race, United States, 2003 to
2009. All White Black
Stage Distribution for Melanoma US 2000-2011 from NCDB 45 41%
40 35 30 25 23% 20 12.5% 15 8% 10 3.85% 5 0 Stage 0 Stage I Stage
II Stage III Stage IV
Stage (Clarks level or Breslow Depth) Current stage system is
based on depth of invasion
Clark Classification (Level of Invasion) Level I: Lesions
involving only the epidermis (in situ melanoma); not an invasive
lesion. Level II: Invasion of the papillary dermis but does not
reach the papillary-reticular dermal interface. Level III: Invasion
fills and expands the papillary dermis but does not penetrate the
reticular dermis. Level IV: Invasion into the reticular dermis but
not into the subcutaneous tissue. Level V: Invasion through the
reticular dermis into the subcutaneous tissue.
Stage System. T or Tumor Category
Stage IA and IB Melanoma T1a = 1mm, no ulceration T1b = 1mm,
ulceration or T2a = 2mm
Treatment Guidelines Early stages: wide local excision More
advanced: wide local excision plus sentinel node biopsy, then based
on the pathology consider research trial, observation or interferon
Metastatic: clinical trial, possible radiation and systemic
therapy
Treatment Guidelines Early stages: wide local excision More
advanced: wide local excision plus sentinel node biopsy, then based
on the pathology consider research trial, observation or interferon
Metastatic: clinical trial, possible radiation and systemic
therapy
Treatment Guidelines Early stages: wide local excision More
advanced: wide local excision plus sentinel node biopsy, then based
on the pathology consider research trial, observation or interferon
Metastatic: clinical trial, possible radiation and systemic
therapy
Lymphati c System Which node to biopsy?
Sentinel Node Biopsy Lymph node Sentinel node Sentinel nodes
removed Dye Cancer Lesion on the arm, which axillary node needs to
be
nomograms.mskcc.org/Melanoma/PositiveSentinelNode.asp x
www.lifemath.net/cancer
Treatment Guidelines Early stages: wide local excision More
advanced: wide local excision plus sentinel node biopsy, then based
on the pathology consider research trial, observation or interferon
Metastatic: clinical trial, possible radiation and systemic
therapy
Treatment Guidelines Early stages: wide local excision More
advanced: wide local excision plus sentinel node biopsy, then based
on the pathology consider research trial, observation or interferon
Metastatic: clinical trial, possible radiation and systemic
therapy
Systemic Therapy for Melanoma Until recently the only approved
drugs were chemotherapy (dacarbazine DTIC 9% response) or toxic
immunotherapy with interleukin-2 (IL-2 response rate 16%)
Activating definition of molecular subtypes of melanoma and
provided potential drug targets. BRAF are the most frequent
mutation in cutaneous melanoma. Approximately 40% to 60% Oncogenic
NRAS mutation in 15% to 20% of melanomas c-KIT mutation, or
increased copy number, is associated with mucosal and acral
melanomas (which comprise 6% to 7% of melanomas in Caucasians but
are the most common subtype in the Asian population). CDK4
mutations have been described in approximately 4% of melanomas and
are also more common in acral and mucosal melanomas.
New Therapies for Melanoma
Systemic Therapy for Melanoma Targeted therapies that block
oncogenic pathways. BRAF inhibitors (vemurafenib or debrafenib) MEK
inhibitors (trametinib) or KIT inhibitors (imatinib)
Systemic Therapy for Melanoma Drugs that disrupt immunologic
checkpoints CTLA-4 (cytotoxic T-lymphocyte antigen 4) : ipilimumab
and tremelimumab or PD-1 (programmed death-1) receptor: nivolumab,
lambrolizumab also PD-L1 (the ligand for PD-1)
Median overall survival in the YERVOY (ipilimumab) group was 10
months YERVOY is the only metastatic melanoma therapy proven in a
phase 3 study to deliver a durable longterm survival benefit at 2
years for 24% of patients, with some patients still alive up to 4.5
years*2
Systemic Therapy for Melanoma
Trends in 5 Year Survival for Melanoma by Year and Race Race
1975-77 1987-89 2003-09 White 82% 88% 93% Black 57% 79% 77%
Five-Year Relative Survival Rates for Selected Cancers by Race
and Stage at Diagnosis, United States, 2003 to 2009. All White
Black
Long Term Survival with Melanoma by Depth Breslow Depth