Understanding and treating Malignant Melanoma

1. Malignant Melanoma
Robert Miller MD
www.aboutcancer.com
melanocyte
melanoma
epidermis
dermis

2. 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.

3. 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

4. Melanoma – Gender Distribution - US
Male
Female

5. New Cases
New Cases
43,890 (5%)
34,590 (4%)
Death
Death
6,470
3,240
2014 Data

6. 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

7. Lifetime risk of an American
developing invasive melanoma

8. 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%

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

10. Risk Factors
Freckling
mild
moderate
severe

11. Risk Factors
Sun (Solar) Skin Damage
Severe solar damage

12. Risk Calculator for Melanoma
http://www.cancer.gov/melanomarisktool/

15. Appearance and location of
melanoma

16. Distribution of superficial
spreading melanoma

17. Distribution of Skin Melanomas
Men on their back

18. Distribution of Skin Melanomas
Women on the back legs

19. 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

20. 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

22. 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 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.

23. Superficial Spreading Melanoma

24. Nodular Melanoma

25. Lentigo
Maligna
Melanoma

26. Variety of Melanoma Skin Lesions

27. Twenty images of skin lesions. Images 1-6, 7-13, and
14-20 show atypical, benign, and malignant
lesions, respectively.

28. Recurrent
melanoma
with
subcutaneou
s nodules

29. Stage Distribution Melanoma by
Race, United States, 2003 to 2009.
All
White
Black

30. Stage Distribution Melanoma by
Race, United States, 2003 to 2009.
All
White
Black

31. 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

32. Stage (Clark’s level or Breslow
Depth)
Current stage system is based
on depth of invasion

33. 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.

34. Stage System. T or Tumor Category

38. Stage IA and IB Melanoma
T1a =
1mm, no
ulceration
T1b =
1mm, ulceration
or T2a = 2mm

39. Stage IIA, B, C Melanoma

40. www.melanomacenter.org/melanomastaging/stagesta
rt.cfm

41. Treatment of Melanoma

43. NCCN.com

44. NCCN.org

45. 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

46. 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

48. 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

49. Lymphati
c System
Which node
to biopsy?

50. Sentinel Node Biopsy
Lymph node
Sentinel node
Sentinel nodes
removed
Dye
Cancer
Lesion on the arm, which
axillary node needs to be

51. Injection site
Surgically exposed node

52. nomograms.mskcc.org/Melanoma/PositiveSentinelNode.aspx

53. nomograms.mskcc.org/Melanoma/PositiveSentinelNode.asp
x

54. www.lifemath.net/cancer

56. 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

57. http://www.mayoclinic.org/medicalprofessionals/adjuvant-systemic-therapytools/melanoma

59. 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

60. 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%)

61. 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.

62. New Therapies for Melanoma

63. Systemic Therapy for
Melanoma
Targeted therapies that block oncogenic
pathways.
BRAF inhibitors (vemurafenib or
debrafenib) MEK inhibitors (trametinib) or
KIT inhibitors (imatinib)

65. 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)

66. 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

67. Systemic Therapy for Melanoma

68. 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%

69. Five-Year Relative Survival Rates for
Selected Cancers by Race and Stage at
Diagnosis, United States, 2003 to 2009.
All
White
Black

70. Long Term Survival with
Melanoma by Depth
Breslow Depth
<0.25mm
0.25 - .49mm
0.50 – 0.74mm
0.75mm – 1.0mm
20 Year Survival
98.3%
98.1%
96.2%
89.0%

71. 5 Year Melanoma Survival
Ulceration
Depth
<1.0mm
1.01 – 2.0mm
2.01 – 4.0mm
> 4mm
No Ulceration
91%
77%
63%
45%
95%
89%
79%
67%
Nodes Involved
1
52%
2–3
50%
4 or +
37%
69%
63%
27%

73. www.melanomaprognosis.or
g

75. www.lifemath.net/cancer

77. 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.

78. 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
aboutcancer.com/melanoma_calculators

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