Melanoma for health care professionals, cancer of the skin.

1. Controversies in Melanoma
Prof Ravi Kant, Dr Ajay Yadav, Dr
Vivek Gupta, Dr Vishal Gupta,
Ms Tanmya Stuti Ravi

2. 2
Controversies in Melanoma
• Biology
• Detection-Computer, USG, RT-PCR
• Staging- AJCC 2000 +Prognosis
• SLN Biopsy + ELND
• Surgical margins
• Adjuvant treatment + Vaccines
• Summary

3. 3
Biology of melanoma
development and progression

4. 4
Biology of melanoma
1. Melanocytes →
2. Nevus →
3. Dysplastic nevus →
4. Radial growth phase →
5. Vertical growth phase →
6. Metastases.

5. 5
Melanoma & Nevi
• Class I = Precursor
• Class II = Intermediate
• Class III = VGP tumorigenic
VGP = vertical growth phase

6. 6
Cell cycle regulation in melanoma

7. 7
Expression of defined molecules in
melanoma cell

8. 8
Express adhesions receptors,
Integrins, Adherine, and cellular
adhesions molecules

9. 9
• melanoma cells express N-
adherine instead of E-adherine.
• E-adherine allows melanocytes
to adhere to keratinocytes,
while melanoma cells can not
adhere to keratinocytes

10. 10

11. 11
B- catenin pathway

12. 12
Biology- what is new?
• PTEN pathway = phosphatase and
tensin deleted on chromosome 10 →
• IGF-1 → Akt / PKB
(Oncogene)+PtdIns(3,4)P2→ P13
kinase →growth factor + adhesion
receptor (integrin)

13. 13
Biology – what is new?
• Ras pathway →Grb2/Sos →ras →Raf
→MEK 1,2 →MAPK 1.2
→TCF/SRF/Elk-1 →Proliferation
• As apoptosis is blocked by depriving
• Bad & Caspase-9 from p13 kinase
• Apoptosis turned into growth

14. Naevi

15. 15
Nevus
• Proliferative lesion of
melanocytes
• Scattered along basal layer
• Acquired - mostly
• congenital

16. 16
Naevi : types
1. Lentigo Flat
2. Junctional
3. Compound – slightly elevated
4. Intradermal – papillomatous

17. 17
Naevi: Lentigo simplex-1
• Pigmented macule, <5mm, jet
black color
• In infants & children
• Melanocytic proliferation along
basal layer

18. 18
Naevi: Lentigo simplex-2
• Abundant melanocytes along
basal layer
• Associated with Peutz-Jegher
syndrome
• P-J syndrome = hamartomatous
polypes in GIT +naevi in oral &
buccal mucosa

19. 19
Naevi: Junctional
• Next stage after lentigo
• Macular lesions, < 7mm
• Less deeply pigmented than
lentigo
• Homogenous brown black areas
• Melanocytic proliferation along
basal layer
• Highest malignant potential

20. 20
Naevi: Compound
• Next stage of maturation of
junctional naevi
• In children & adolescent
• Pale brown & papular
• Junctional + dermal
component

21. 21
Naevi: Intradermal
• Last stage in maturation
• Mostly after 30 years of age
• Flesh colored papule with little
pigment
• Melanocytes confined to
dermis only

22. 22
Blue naevi
• Benign melanocytic naevi
• Slate blue color
• Two types : common & cellular

23. 23
Common Blue naevi
Mostly in scalp & dorsum of hand, feet
1. Dermal collection of spindle
melanocytes
2. F > M , max. in 4th decade

24. 24
Blue naevi: Cellular type
1. Uncommon
2. F > M
3. > 50% in sacrococcygeal area&
buttock
4. < 1% under go malignancy
5. Rx : simple excision

25. 25
Nevus
• Common
• Atypical
• Congenital
• Spitz
• Familial

26. 26
Malignant Melanoma
• Arises from transformed melanocytes
of epidermis
• Accounts for almost all deaths from
skin cancer
• 4 fold increase in incidence in
Australia

27. 27
Melanoma : Risk Factors-1
• Congenital naevi >5% BSA, 1000X
• Previous melanoma
• Family history
• 5 naevi > 5mm (Common nevi)
• 50 naevi > 2mm (Common nevi)

28. 28
Melanoma : Risk Factors-2
• Dysplastic nevi, Atypical= 2X for
single; 12X for >10
• Family history Atypical =37-148X
• Dysplatic naevi syndrome

29. 29
Melanoma : Risk factors-3
• White race,
• Red hair,
• Blond hair,
• Blue eyes
• Poor tanning ability,
• Sunburns during childhood
• Albinism

30. 30
Melanoma : Risk factors-4
• Freckles
• Equatorial latitude
• Xeroderma pigmentosa
• Psoralen sunscreen
• Tanning salons
• Junctional naevi

31. 31
Melanoma : Risk factors-5
• Spitz Nevi= benign except when
>10 y age
+ulceration
>1cm
Involve subcut fat
Mitotic activity >6/mm2

32. 32
Melanoma : Risk factors-6
• Familial syndromes
• B-K nevus syndromes
• Atypical nevus
• CDKN2A mutation
• CDK4 mutation

33. 33
DD
• Pigmented Basal cell CA
• Seborrheic keratitis
• Solar lentigines
• Atypical nevi

34. 34
MM: Clinical features
• Lentigo maligna : Hutchinson's
freckle (7-15%)
• Superficial spreading : most
common (60-70%)
• Nodular : 12-25%
• Acral lentiginous
• Amelanotic

35. 35
1. Superficial spreading
Melanoma
• Most common type 70%
• Occur any where on skin except
hands & feet
• Usually > 5 mm , flat
• Variegated color pattern
• Irregular edge with areas of
regression
• Long radial growth phase

36. 36
2. Nodular Melanoma
• Most malignant
• Younger age group
• Any part of the body
• raised and always palpable with sharp
irregular border
• Blue, black or gray color
• Lack of radial growth phase

37. 37
2. Nodular Melanoma
• Second most common 15-30 %
• Rapid onset
• ♂>♀

38. 38
3. Lentigo maligna Melanoma
• Hutchinsons melanotic freckle
• Least common type 5%
• Most commonly on face of elderly
• Begins as irregularly pigmented ,flat,
brown macule
• quite large at the time of diagnosis late
invasive growth phase
• Good prognosis

39. 39
4. Acral lentiginous
• Uncommon 1-3%
• Palm, sole, heel & subungual
• More common in dark skin
persons
• Subungual –common in big toe or
thumb
• Poor prognosis , 29%@20Y
• 70% ulcerate, 74% >1.5 mm

40. 40
4. Acral lentiginous-risk factor
• >50 y age
• >3mm width, variegated border
• Extension of pigment in to nail
bed/ nail fold
• Dark complexioned patient

41. 41
5. Amelanotic Melanoma
• Desmoplastic, 1.7%
• H&N
• Pink, reveal some pigment on close
inspection; Stain+ with S-100
• Worse prognosis
• Often present with regional lymph
nodes metastases

42. 42
5. Amelanotic Melanoma
• Locally aggressive
• Known for local recurrences
• Stain ► S-100

43. 43
MM : spread
• Local extension
• Blood stream : lung, liver, brain, skin
• Lymphatic :
– embolisation, permeation
– satellite nodule
– in-transit nodule

44. 44
Controversies in Melanoma
• Biology
• Detection-Computer, USG, RT-PCR
• Staging- AJCC 2000 +Prognosis
• SLN Biopsy + ELND
• Surgical margins
• Adjuvant treatment + Vaccines
• Summary

45. 45
MM : Diagnosis
• Signs of transformation of mole in to MM
• Major
–Change in size, shape, color
• Minor
–Inflammation, itching
–Crusting or bleeding
– > 5mm diameter

46. 46
MM: Diagnosis
• A : Asymmetry
• B : irregular border
• C : color variegation
• D : diameter > 5 mm
• E : enlargement or evolution

47. 47
Detection- Vision
• A = asymmetry
• B = border irregularity
• C = color variegation
• D =diameter > 6mm
• E = elevation, enlargement,
evolutionary changes
• F= any funny change

48. 48
Detection- Vision
1. Change in size
2. Change in shape
3. Change in Color
4. Inflammation
5. Crusting / bleeding
6. Sensory change
7. > 7mm in size enlargement

49. 49
Detection- Digital Vision
• Epiluminescence microscopy
• Dermatoscopy
• Surface microscopy
• Incident light microscopy
• Can see the dermis, epidermo-dermal
junction

50. 50
Epiluminescence microscopy
-ominous signs
• Melanin pigment
network
• Black dots
• Globules
• Streaks
• Radial streaming
• Blue-white milky
veils
• Pseudopods
• Pseudo network
• Structure less area
• Melanin reticulum
• Epidermo-dermal
junction
• Multiple brown dots

51. 51
Epiluminescence microscopy
-good signs
• Axial symmetry of pigmentation
• Presence of one color only
• Sensitivity 92%
• Specificity 71%

52. 52
Detection-digital vision
• Computer based Dermatoscopy
• Spectrophotometric image analysis
• Reflectance spectroscopy
• Computer aided image analysis
Topodermatographic
• USG, MR and OCT = in vivo histology
• Virtual histology

53. 53
USG for Regional LN
• 7.5-20 mhZ for LN : 20-100 for Virtual
• USG B scan-LN
• Vassallo index<2 (Long:Trans)
• Hypoechoic central area
• Color Doppler-peripheral perfusion
• USG Guided FNAC +RT-PCR Tyro
• USG guided anchor wire for mets

54. 54
Screening
Dermatologist
or
non-Dermatologists?

55. 55
Screening
Dermatologist
• sensitivity 89% - 97%
• positive predictive value - 17-75%
• specificity - 97%

56. 56
PET vs CT
Sensitive
%
Specificity
%
FDG PET 94-100 83 -94
CT 55-84 68-84
Holder
Ann Surg 1998
Rinne
Cancer 1998

57. 57
FDG PET >CT
• regional and mediastinum
lymph nodes
• abdominal visceral and soft
tissue metastasis

58. 58
Lung mets
87 vs 70 %
CT>PET

59. 59
MRI for brain

60. 60
A single whole body PET scan
could replace all other imaging
modalities in melanoma.
PET

61. 61
1. Cost
2. Limited availability
3. Lack of sufficient data
Limitations of PET

62. 62
Controversies in Melanoma
• Biology
• Detection-Computer, USG, RT-PCR
• Staging- AJCC 2000 + Prognosis
• SLN Biopsy + ELND
• Surgical margins
• Adjuvant treatment + Vaccines
• Summary

63. 63
Prognostic factors
Tumor thickness = Breslow
Vs
Level of invasion = Clark level

64. 64
Thickness vs. Level
54 multivariate analysis of
prognostic factors using data
from 48 papers
Vollmer

65. 65
Thickness vs. Level
Tumor thickness significant
in 42 of 54 studies
Vollmer

66. 66
Thickness vs. Level
Level of invasion important
prognostic factor in only 8 of 48
Studies
Vollmer

67. 67
Thickness vs. Level
• Tumor thickness
• 1 , 2, & 4 mm
• Best for survival data
• Adopted in 2002 AJCC
Buttner
Buzaid

68. 68
Thickness vs. Level-
conclusion
• Clark level of invasion is a minor
prognostic factor
• cutoffs of tumor thickness
such as 1mm, 2mm and 4mm
provide better prognostic
information
• 2002 AJCC staging of melanoma

69. 69
Ulceration: prognostic significance
Significant prognostic factor
Vollmer - multivariate analysis in
7 of 11 studies

70. 70
Ulceration: prognostic significance
strongest predictors of outcome
Balch - meta-analysis that
included 15,798 patients with
localized melanoma

71. 71
Ulceration: prognostic significance
• Ulceration has the most
significant impact on survival.
• Buzaid : influence of ulceration
according to the tumor
thickness

72. 72
Ulceration
• Acantholysis
• Shows autocrine and paracrine
pathways are active
• Adverse prognosis

73. 73
Ulceration: prognostic significance
• Independent prognostic factor
• Included in AJCC 2002 staging
• Upstage patients compared
with those having tumor of
same thickness

74. 74
Satellites vs. In-transit metastases
• In transit and satellite metastases
common manifestations of
intralymphatic metastasis
• associated with poor prognosis

75. 75
Satellites vs. In-transit metastases
prognosis of patient with
satellites is usually worse than
that of patient with in-transit or
nodal metastasis (stage III)
Buzaid J Clin Oncol 1997
Haffner Br J Cancer 1992
Cascinelli J Surg Oncol 1986

76. 76
Satellites vs. In-transit metastases
• Satellites =
• pT4b (1997)  N2c / N3 (2002)
• Stage II  stage III

77. 77
Lymph node size vs. number-
Prognostic value
Size not a significant prognostic
factor even after stratification
according to cutoff size
Drepper Cancer 1993
Buzaid J Clin Oncol 1995

78. 78
Lymph node size vs. number-
Prognostic value
Number of LN most consistent
prognostic factor by
multivariate analysis
Buzaid J Clin Oncol 1997

79. 79
Author Pt No OS
%
Survival % by LN no
1 2-4 5 or ↑
Buzaid 95 442 42 55 34 25
Drepper
93
112 39 47 31 20
Singletary
92
264 NS 45 31
Balch 92 234 NS 40 28 18
Coit 91 449 32 40 40 19

80. 80
Lymph node number-Prognostic
value
• number of positive nodes
has replaced size of lymph
node mass
Current 2002 AJCC staging system.

81. 81
Lymph node number-Prognostic
value
N1 = 1 LN
N2 = 2 or 3 LNs
N3 =  4 LNs
AJCC 2002 staging

82. 82
Prognostic Value of Biochemical
& serologic markers
Significant prognostic factor in
melanoma
• LDH
• S-100-B
• melanoma inhibitory activity
serum markers

83. 83
Prognostic Value of Biochemical
& serologic markers
After logistic regression analysis,
LDH is found to be the only
statistically significant marker
for progressive disease and the
most relevant overall parameter

84. 84
Prognostic Value of Biochemical
& serologic markers
• AJCC staging 2002 includes
LDH
• Distant metastases + elevated
serum LDH = M1c category
• Two or more reports = > 24 hrs
apart.

85. 85
Prognostic Markers-1
• Micro stage
• Breslow 1,2,4
• Clark levels
• Ulceration
• Mitotic figures
• Inflammatory
regression
• Micro satellites
• Vertical growth
fraction
• Tumor infiltrating
lymphocytes
• Molecular
markers
• Micro staging
approaches

86. 86
Prognostic Markers-2
• S phase fraction
• Mitotic index
• Ulceration
• RT-PCR +
• Tyrosinase or
• MelanA or
• MART1 m rna
• Integrins: β3
subunit of
vitronectin-
receptor for
Vertical growth
phase
• Β1integrin for LN
mets

87. 87
Prognostic Markers-3
• MMP-2 ↑=☼
• VEGF ↑=☼
• Mitf=
Microphtalmia
transcription
factor ↑=☺
• CD 40 + =☼
• CD 40 L+ CD 40
= worse
prognosis

88. 88
Prognostic Markers-4
• Mutation in
Codon 12 or 61
of N-ras = ☼ =
↓ OS
• Mutation in
Codon 18 of N-
ras exon 1 = ☺
(No mets)
• Transcription
factor = Activator
Protein-2=AP-2
• Regulates gene
in cell cycle and
growth control
• ↓ AP-2= ↓ p21=
↓ RFS & ↓OS

89. 89
MM : prognostic factors
• Depth of invasion (BRESLOW)
• Ulceration
• High mitotic rate
• Anatomic location
• Histologic type
• Lymphoid & dendritic cell infiltration
• regression

90. 90
Depth of invasion in mm:
Breslow
I  1
II 1-2
III 2-4
IV >4

91. 91
Depth of invasion : Clark
• I : superficial to basement
membrane
• II : papillary dermis
• III : papillary/reticular dermis junction
• IV : reticular dermis
• V : subcutaneous fat

92. 92
Controversies in Melanoma
• Biology
• Detection-Computer, USG, RT-PCR
• Staging- AJCC 2000 +Prognosis
• SLN Biopsy + ELND
• Surgical margins
• Adjuvant treatment + Vaccines
• Summary

93. 93
Elective LN dissection
Persistent area of controversy
Micro metastases in Clinically N-
= 14% -20%

94. 94
Arguments for Elective LN dissection
retrospective + prospective studies
Goldsmith
Memorial hospital
1552 patients
5 yr survival
78% vs. 68%

95. 95
Melanoma Inter-group Trial 1996
• 700 patients
• Prospective study
• Significantly improved survival rates
with ELND in a subgroup = <60 years,
non-ulcerated 1-4 mm
Balch : Ann Surg 1996

96. 96
Balch Cancer 1979
At 5 Year Distant
Metastases
Survival
ELND 15% 83%
TLND 78% 37%

97. 97
Survival advantage ?
Positive nodes after ELND 16%
Slingluff Ann Surg 1994

98. 98
Elective LN dissection: no benefit
WHO 1998 Prospective
Intergroup Melanoma
1996
Prospective
Mayo Clinic, 1986 Prospective
WHO, 1977 Prospective
Sydney melanoma, 1995 Retrospective
Duke university, 1994 Retrospective
University of
Pennsylvania,1985
Retrospective

99. 99
Elective LN dissection: benefit
Romple, 1995 Retrospective
Drepper, 1993 Retrospective
Sydney melanoma
unit, 1985
Retrospective
Duke university,
1983
Retrospective
University of
Alabama, 1982
Retrospective
Memorial, 1975 Retrospective

100. 100
ELND
or
Sentinel LN biopsy ?

101. 101
Sentinel Lymph Node Biopsy
Sensible approach
In view of low occult metastasis - 12-
15% ; It allows upto 85% of patients
with melanoma to be spared a formal
lymph node dissection, thus
avoiding complication associated
with that procedure

102. 102
SLN biopsy
• 100% sensitive
• 97% specific
Pu Plast Reconstruct Surg 1999

103. 103
• No decrease in survival
compared with patients
undergoing ELND
• Therapeutically equivalent but
prognostically more accurate
than ELND
Essner Ann Surg Oncol 1999

104. 104
SLN Indications:
• 5-10% risk of mets to Node
• Candidate for High dose interferon
alfa-2b
• Melanoma < 1mm thickness but
Clarke level III or ↑ (10% risk of
recurrence)

105. 105
• Primary tumors between 1mm
and 4mm thickness
• up to 45% incidence of occult
nodal metastases

106. 106
SLN: Contraindication-1
1. < 1 mm thickness melanoma
(< 2% N or M)
2. > 4mm thickness melanoma,
Clinically N-
(as 60-70% N & occult M 70%)

107. 107
SLN: Contraindication-2
• FNAC + LN
• Prior wide excision of primary

108. 108
SLN Micromets: Significance
Gershenwald 1999 J Clin Oncol
+SLN= 23% rec rate; 16% death rate
- SLN=9% recurrence rate, 35% death
Clary 2001, Ann Surg 233:250-258
+SLN=40% recurrence, 58%DFS@3y
-SLN=14% recurrence, 75%DFS@3y

109. 109
SLN Micromets: Significance
Short term DFS ↑ : HE-, IH-, RT PCR+
Short term DFS ↓ : HE-, IH-, RT PCR+

110. 110
SLN
Method Success
in %
Blue dye 70-82
Isotope 84-94
Both 96-98
False +
in %
False-
in %
0,5, 27

111. 111
Blue dye for SLN
• Patent blue V & Isosulfan blue
• Anaphylaxis in 3 / 406 cases
• Incidence with Isosulfan blue =1%
• Prepared for anaphylaxis treatment

112. 112
Blue dye for SLN
• 2-5 ml of 1% Isosulfan blue into the
dermis (not sub cut) around the intact
tumor + Exercise+ 5-15 minutes wait
• Clears from SLN within 45 minutes

113. 113
Isotope
• Tc 99m labeled sulfur colloid
• 100 μm filtered Tc 99m labeled sulfur
colloid- even better
• 99m Tc DTPA mannosyl-dextran →
affinity for lymph node; avoid distal
lymph node imaging
• 3 hours prior injection, intradermally
around the tumor

114. 114
Isotope
• Allows dissection down to the LN
without need to create flaps
• Keep hand held array at an angle=
avoid “Shine Through”
• If ↑ 3:1 resection bed : background
ratio = search more SLN

115. 115
SLN
• H/E stain
• Immunohistochemistry to S-100
protein, HMB-45 antigen,
• RT-PCR Tyrosinase, Mel A
• 14% are HE – and + by IH
• 20-30% are HE-, IH- but RT-PCR+
• Cell culture technique

116. 116
Controversies in Melanoma
• Biology
• Detection-Computer, USG, RT-PCR
• Staging- AJCC 2000 +Prognosis
• SLN Biopsy + ELND
• Surgical margins
• Adjuvant treatment + Vaccines
• Summary

117. 117
• In situ 5 mm
• <2mm 1cm
• >2mm 2cm
Sober AJ : J Am Acad Dermatol 2001
Current recommendations for
surgical margins: primary
cutaneous melanoma :
thickness based decision

118. 118
Diameter, Location & Surgical
Margins : Zitelli 1997
Location
►
Head &
Neck, Hand
Trunk &
Extremity
Size in cm
↓
Margin in cm ↓ Margin in cm ↓
< 2 1.5 1
>2 2.5 1.5

119. 119
Surgical margins
No significant difference in
survival for excision margin 2
cm or 4 cm for tumor between
1mm and 4mm
Balch Ann Surg 1993

120. 120
Tumor thickness =1-2 mm
Margin 1cm or 3cm
OS same
Margin: WHO Melanoma group

121. 121
No significant difference in
survival for margins 2 or 5 cm for
tumors between 0.6 mm to 2mm
Swedish melanoma group.
Cancer 1998
Margin 2 or 5 cm

122. 122
Mohs Micrographically controlled
Surgery
• In situ fixation- earlier by ZnO
• Now micrography-sectioned and
inked and oriented=mapped

123. 123
Controversies in Melanoma
• Biology
• Detection-Computer, USG, RT-PCR
• Staging- AJCC 2000 +Prognosis
• SLN Biopsy + ELND
• Surgical margins
• Adjuvant treatment + Vaccines
• Summary

124. 124
No Role of prophylactic
(adjuvant)
Isolated Limb Perfusion

125. 125
EORTC
WHO
North American Perfusion Group
No improvement in survival
Isolated Limb Perfusion

126. 126
Therapeutic isolated limb
perfusion
• Better DFS
• No significant change in OS
Hafstrom J Clin Oncol 1991

127. 127
Who are candidates for ILP?

128. 128
Therapeutic
Patients with in transit disease
confined to a limb, with no
signs of distant metastases at
presentation.

129. 129
Drugs for ILP
• DTIC + Others
• Melphalan +others
• TNF ά
• Interferon

130. 130
Palliative
Bulky regional disease with
limited systemic metastases

131. 131
• identified by prognostic
factors or
• identified by sentinel lymph
node biopsy.
Clark : J Natl Cancer Inst 1989
Adjuvant Indications:
↑risk for metastatic disease

132. 132
High risk melanoma: Interferon
• Thickness >4mm
• Mitotic index
• Location
• Gender
• Ulceration
• +SLN
• AP-2 index

133. 133
Interferon 2b
• √ US FDA for high risk melanoma
• ↓Recurrence
• Interferon alpha2b ▲DFS , ▲ OS by
EOCG HDI 1684, EOCG1690 and
French LDI Grob 2000- in selected
cases

134. 134
• high dose interferon alpha 2b
• tamoxifen,
• cisplatin, and
• Vindesine
• GM CSF
• Levamisole.
Adjuvant ?

135. 135
• TNF
• Interleukin-2
• Biochemotherapy
• Cytokines
• Ab3
• Peptide based vaccines
• MAGE tumor specific shared ag
Adjuvant ?

136. 136
What are New Options
• Biochemotherapy
• DTIC or temozolomide+Nitrosureas
• Interferon = antiproliferative and
immunomodulatory
• Interleukin-2 =Immunostimulatory
cytokine ►NK cells

137. 137
Vaccines
• Vaccines-ganglioside GM2
• MAGE Tumor specific antigens
• Ab3 a cytokine
• Antibody based vaccines
• HLA based
• Cell based vaccines
• Peptide vaccines
• Recombinant viruses

138. 138
Controversies in Melanoma
• Biology
• Detection-Computer, USG, RT-PCR
• Staging- AJCC 2000 +Prognosis
• SLN Biopsy + ELND
• Treatment margins
• Adjuvant treatment + Vaccines
• Summary

139. 139
Major changes in AJCC
classification in 2002 -1
• √ Thickness
• X not levels
• √ Ulceration
• √ Number of LN
• X size of LN
• √ LDH

140. 140
Major changes in AJCC
classification in 2002-2
• √ Upstaging with ulceration
• √ Merge micro satellite & in-transit
mets into stage III
• √ Include SLN into staging

141. 141
Major changes
• Ultrasound of LN
• RT-PCR Tyrosinase of SLN
• 1→ 106–109
• Detect 1 cancer cell out of 106 – 109
normal cells
• Thin margins
• Adjuvant interferon +/-

142. 142
• In situ 5 mm
• <2mm 1cm
• >2mm 2cm
Sober AJ : J Am Acad Dermatol 2001
Current recommendations for
surgical margins: primary
cutaneous melanoma

143. 143
Summary
• No role of wide margins
• No role of ELND
• No role of Prophylactic ILP
• Role of SLN
• Interferon alpha2b ▲DFS , ▲ OS
→ EOCG HDI 1684, EOCG1690
& French LDI Grob 2000- in selected cases

144. 144
Summary Rx
• Primary surgical
• Surgical principles
Complete surgical excision
Minimum margin 1.0 cm
Maximum margin 2.0 cm
Do not excise beyond deep
fascia

145. 145
MM :– management of lymph
nodes
• Biopsy : FNAC preferred
• Elective dissection : for
1. Clinically involved nodes,
2. Satellitosis,
3. Lymphatic invasion

146. 146
Sentinel lymph node biopsy
• Detects micrometastasis in lymph
nodes
• Inrtadermal injection of radioactive
colloid around lesion
• Lymph node identified by gamma
probe

147. 147
Sentinel lymph node biopsy
• Intraoperative identification by
using patent blue dye
• Identify patients appropriate for
elective dissection
• Identify patients among high risk
for adjuvant interferon.

148. 148
Thank You