Maligna Melanoma

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
Male Female
Melanoma – Gender Distribution - US
2014 Data
New Cases

43,890 (5%)

Death

6,470
New Cases

34,590 (4%)

Death

3,240
0
0.05
0.1
0.15
0.2
0.25
20 30 40 50 60 70 80 90
Age Distribution
Age Distribution
US (2000-2011) from the NCDB
Lifetime risk of an American
developing invasive melanoma
Probability (%) of Getting
Melanoma (2008-2010)
Age Men Women

0-49 0.4 0.5
50-59 0.4 0.3
60-69 0.8 0.4
70+ 2.1 0.9

Lifetime 2.9% 1.9%

SEER database from 2000 to 2004, the male incidence rates per
100,000
0
5
10
15
20
25
30
white hispanic asian black
Melanoma by Race
Risk Factors

Freckling
mild
moderate
severe
Risk Factors
Sun (Solar) Skin Damage
Severe solar damage
http://www.cancer.gov/melanomarisktool/
Risk Calculator for Melanoma
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,
bowel 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,
bowel spread) liver
biopsy showed
metastatic
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 ¼ 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.
Possible signs and
symptoms of melanoma
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
0
5
10
15
20
25
30
35
40
45
Stage 0 Stage I Stage II Stage III Stage IV
Stage Distribution for Melanoma –
US 2000-2011 from NCDB
23%
3.85%
8%
12.5%
41%
Stage (Clark’s 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
Stage IIA, B, C Melanoma
Stage IA and IB Melanoma
T1a =
1mm, no
ulceration
T1b = 1mm,
ulceration or T2a
= 2mm
www.melanomacenter.org/melanomastaging/stagesta
rt.cfm
Treatment of Melanoma
NCCN.com
NCCN.org
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
Dye
Cancer
Sentinel node
Sentinel nodes
removed
Lesion on the arm, which
axillary node needs to be
biopsied?
Injection site Surgically exposed node
nomograms.mskcc.org/Melanoma/PositiveSentinelNode.aspx
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
http://www.mayoclinic.org/medical-
professionals/adjuvant-systemic-therapy-
tools/melanoma
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 long-
term 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 20 Year Survival

<0.25mm 98.3%
0.25 - .49mm 98.1%
0.50 – 0.74mm 96.2%
0.75mm – 1.0mm 89.0%
5 Year Melanoma Survival
Ulceration No Ulceration
Depth
<1.0mm 91% 95%
1.01 – 2.0mm 77% 89%
2.01 – 4.0mm 63% 79%
> 4mm 45% 67%

Nodes Involved
1 52% 69%
2 – 3 50% 63%
4 or + 37% 27%

www.melanomaprognosis.or
g
www.lifemath.net/cancer
Cellular Classification of Melanoma

Following is a list of clinicopathologic cellular subtypes of
malignant melanoma. These should be considered
descriptive terms of historic interest only as they do not
have independent prognostic or therapeutic significance.

Superficial spreading.
Nodular.
Lentigo maligna.
Acral lentiginous (palmar/plantar and subungual).
Miscellaneous unusual types:
Mucosal lentiginous (oral and genital).
Desmoplastic.
Verrucous.

aboutcancer.com/melanoma_calculators


Melanoma staging tool here
Memorial Sloan Kettering clinic has lymph
node calculators for melanoma here

Mayo clinic calculator for the benefit of
adjuvant interferon here
NCI, the risk of getting it melanoma here
MGH has calculators for melanoma (survival
and risk of lymph node spread) here
Prognosis for melanoma here
Risk of getting melanoma from Harvard here

Melanoma Calculators
Malignant Melanoma
Robert Miller MD
www.aboutcancer.com