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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 w...
Most Common Skin Cancers in 2013
Basal Cell : 2,800,000 (78%)
Squamous: 700,000 (20%)
Melanoma:
76,690 (2%)

Between 40 an...
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...
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

L...
30

Melanoma by Race

25
20
15
10
5
0
white

hispanic

asian

black

SEER database from 2000 to 2004, the male incidence r...
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,...
45 yo man with
‘mole’ on his back
for years presented
with headaches
and was found to
have widespread
(brain, liver, lung,...
Possible signs and
symptoms of melanoma
A is for Asymmetry: One half of a mole or birthmark
does not match the other.
B is...
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...
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...
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
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, t...
Treatment Guidelines
• Early stages: wide local excision
• More advanced: wide local
excision plus sentinel node
biopsy, t...
Treatment Guidelines
• Early stages: wide local excision
• More advanced: wide local
excision plus sentinel node
biopsy, t...
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...
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, t...
http://www.mayoclinic.org/medicalprofessionals/adjuvant-systemic-therapytools/melanoma
Treatment Guidelines
• Early stages: wide local excision
• More advanced: wide local
excision plus sentinel node
biopsy, t...
Systemic Therapy for
Melanoma

• Until recently the only approved
drugs were chemotherapy
(dacarbazine DTIC 9% response)
o...
Activating definition of molecular subtypes
of melanoma and provided potential drug
targets.
BRAF are the most frequent mu...
New Therapies for Melanoma
Systemic Therapy for
Melanoma
Targeted therapies that block oncogenic
pathways.
BRAF inhibitors (vemurafenib or
debrafenib...
Systemic Therapy for
Melanoma

Drugs that disrupt immunologic
checkpoints
CTLA-4 (cytotoxic T-lymphocyte antigen
4) : ipil...
Median overall survival in the YERVOY (ipilimumab)
group was 10 months
YERVOY is the only metastatic melanoma therapy
prov...
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%
7...
Five-Year Relative Survival Rates for
Selected Cancers by Race and Stage at
Diagnosis, United States, 2003 to 2009.

All
W...
Long Term Survival with
Melanoma by Depth
Breslow Depth
<0.25mm
0.25 - .49mm
0.50 – 0.74mm
0.75mm – 1.0mm

20 Year Surviva...
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%
...
www.melanomaprognosis.or
g
www.lifemath.net/cancer
Cellular Classification of Melanoma
Following is a list of clinicopathologic cellular subtypes of
malignant melanoma. Thes...
Melanoma Calculators
Melanoma staging tool here
Memorial Sloan Kettering clinic has lymph
node calculators for melanoma he...
Malignant Melanoma
Robert Miller MD
www.aboutcancer.com
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Understanding and treating Malignant Melanoma

Published in: Health & Medicine
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Melanoma video slides

  1. 1. Malignant Melanoma Robert Miller MD www.aboutcancer.com melanocyte melanoma epidermis dermis
  2. 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. 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. 4. Melanoma – Gender Distribution - US Male Female
  5. 5. New Cases New Cases 43,890 (5%) 34,590 (4%) Death Death 6,470 3,240 2014 Data
  6. 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. 7. Lifetime risk of an American developing invasive melanoma
  8. 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. 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. 10. Risk Factors Freckling mild moderate severe
  11. 11. Risk Factors Sun (Solar) Skin Damage Severe solar damage
  12. 12. Risk Calculator for Melanoma http://www.cancer.gov/melanomarisktool/
  13. 13. Appearance and location of melanoma
  14. 14. Distribution of superficial spreading melanoma
  15. 15. Distribution of Skin Melanomas Men on their back
  16. 16. Distribution of Skin Melanomas Women on the back legs
  17. 17. 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
  18. 18. 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
  19. 19. 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.
  20. 20. Superficial Spreading Melanoma
  21. 21. Nodular Melanoma
  22. 22. Lentigo Maligna Melanoma
  23. 23. Variety of Melanoma Skin Lesions
  24. 24. Twenty images of skin lesions. Images 1-6, 7-13, and 14-20 show atypical, benign, and malignant lesions, respectively.
  25. 25. Recurrent melanoma with subcutaneou s nodules
  26. 26. Stage Distribution Melanoma by Race, United States, 2003 to 2009. All White Black
  27. 27. Stage Distribution Melanoma by Race, United States, 2003 to 2009. All White Black
  28. 28. 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
  29. 29. Stage (Clark’s level or Breslow Depth) Current stage system is based on depth of invasion
  30. 30. 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.
  31. 31. Stage System. T or Tumor Category
  32. 32. Stage IA and IB Melanoma T1a = 1mm, no ulceration T1b = 1mm, ulceration or T2a = 2mm
  33. 33. Stage IIA, B, C Melanoma
  34. 34. www.melanomacenter.org/melanomastaging/stagesta rt.cfm
  35. 35. Treatment of Melanoma
  36. 36. NCCN.com
  37. 37. NCCN.org
  38. 38. 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
  39. 39. 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
  40. 40. 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
  41. 41. Lymphati c System Which node to biopsy?
  42. 42. Sentinel Node Biopsy Lymph node Sentinel node Sentinel nodes removed Dye Cancer Lesion on the arm, which axillary node needs to be
  43. 43. Injection site Surgically exposed node
  44. 44. nomograms.mskcc.org/Melanoma/PositiveSentinelNode.aspx
  45. 45. nomograms.mskcc.org/Melanoma/PositiveSentinelNode.asp x
  46. 46. www.lifemath.net/cancer
  47. 47. 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. 48. http://www.mayoclinic.org/medicalprofessionals/adjuvant-systemic-therapytools/melanoma
  49. 49. 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
  50. 50. 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%)
  51. 51. 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.
  52. 52. New Therapies for Melanoma
  53. 53. Systemic Therapy for Melanoma Targeted therapies that block oncogenic pathways. BRAF inhibitors (vemurafenib or debrafenib) MEK inhibitors (trametinib) or KIT inhibitors (imatinib)
  54. 54. 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)
  55. 55. 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
  56. 56. Systemic Therapy for Melanoma
  57. 57. 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%
  58. 58. Five-Year Relative Survival Rates for Selected Cancers by Race and Stage at Diagnosis, United States, 2003 to 2009. All White Black
  59. 59. 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%
  60. 60. 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%
  61. 61. www.melanomaprognosis.or g
  62. 62. www.lifemath.net/cancer
  63. 63. 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.
  64. 64. 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
  65. 65. Malignant Melanoma Robert Miller MD www.aboutcancer.com

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