MALIGNAN

MALIGNAN
T
T
MELANOM
MELANOM
A
A

Malignant Melanoma
Malignant Melanoma

Introduction
Introduction

Epidemiology
Epidemiology

Types
Types

Invasion and Metastasis

Invasion and Metastasis

Risk Factors
Risk Factors

Diagnosis and Staging

Diagnosis and Staging

Treatment and Prevention

Treatment and Prevention

Skin:
Skin:
Epidermis -
Epidermis -
Melanocytes
Melanocytes

Melanocytes: Melanocytes:

In stratum basale In stratum basale

Pale !alo" o# cytoplasm Pale !alo" o# cytoplasm

$eural crest $eural crest

Produce melanin and pass Produce melanin and pass

it on to nearby it on to nearby
keratinocytes keratinocytes

Melanin covers nuclei o# Melanin covers nuclei o#

nearby keratinocytes nearby keratinocytes

Skin colour depends on Skin colour depends on

melanocytes activity% melanocytes activity%
rat!er t!an t!e number rat!er t!an t!e number
present present

Epidemiology
Epidemiology
Trent &'((() Trent &'((()
Incidence
Incidence
Mortality
Mortality
Male Male Femal Femal
e e
Male Male Femal Femal
e e
$umber $umber '*+ '*+ ,'- ,'- .+ .+ ./ ./
0rude Rate Per 0rude Rate Per
'11%111 '11%111
-21 -21 /2/ /2/ ,2, ,2, ,2* ,2*
3ge Standardised 3ge Standardised
Rate Per '11%111 Rate Per '11%111
.2+ .2+ 42/ 42/ ,21 ,21 '24 '24

Epidemiology
Epidemiology
3ge Speci5c Incidence Rates Trent '(((% Trent 0ancer Registry

Types
Types

Super5cial spreading MM &SSMM)

Super5cial spreading MM &SSMM)

6entigo maligna melanoma&6MM)

6entigo maligna melanoma&6MM)

$odular MM &$MM)
$odular MM &$MM)

3cral lentiginous MM &36MM)

3cral lentiginous MM &36MM)

Superfcial Spreading
Superfcial Spreading
Malignant Melanoma
Malignant Melanoma

417 o# all melanomas

417 o# all melanomas

Raised irregular margin

Raised irregular margin

8nevenly pigmented
8nevenly pigmented

9ecomes nodular on invasion% :!ic! is

9ecomes nodular on invasion% :!ic! is
common
common

0ells spread bet:een epidermal ridges

0ells spread bet:een epidermal ridges
via dermal papillae unlike benign lesions
via dermal papillae unlike benign lesions

Early detection leads to (.7 . year

Early detection leads to (.7 . year
survival rate
survival rate

Superfcial Spreading
Superfcial Spreading
Malignant Melanoma
Malignant Melanoma


Lentigo Maligna
Lentigo Maligna
Melanoma
Melanoma

Initially lentigo maligna &;utc!inson<s

Initially lentigo maligna &;utc!inson<s
#reckle)
#reckle)

'17 o# all melanomas

'17 o# all melanomas

0!ronic sun=e>posure to skin

0!ronic sun=e>posure to skin

Starts ?at and pigmented% becoming

Starts ?at and pigmented% becoming
nodular on invasion
nodular on invasion

0olour tan to black% areas o# blue and red

0olour tan to black% areas o# blue and red

8neven% sunken margin

8neven% sunken margin

6ate presentation makes it di@cult to

6ate presentation makes it di@cult to
e>cise
e>cise

Lentigo Maligna
Lentigo Maligna
Melanoma
Melanoma


Nodular Malignant
Nodular Malignant
Melanoma
Melanoma

'1='.7 o# all melanomas

'1='.7 o# all melanomas

Raised and nodular

Raised and nodular

Accasional ulceration
Accasional ulceration

Pigmentation is generally !eavy% t!oug!

Pigmentation is generally !eavy% t!oug!
occasionally t!ere is no pigmentation =
occasionally t!ere is no pigmentation =
3melanotic malignant melanoma
3melanotic malignant melanoma

$MM in5ltrates t!e epidermis #ast

$MM in5ltrates t!e epidermis #ast

Tumour cells eit!er epit!eliod or spindle cell

Tumour cells eit!er epit!eliod or spindle cell

Mitotic 5gures in t!e dermis component o#

Mitotic 5gures in t!e dermis component o#
lesions con5rm malignancy
lesions con5rm malignancy

Nodular Malignant
Nodular Malignant
Melanoma
Melanoma


Acral Lentiginous
Acral Lentiginous
Malignant Melanoma
Malignant Melanoma

Palmar plantar mucosal melanoma Palmar plantar mucosal melanoma

0ommon in 3sian and 3#rican populations 0ommon in 3sian and 3#rican populations

+ = .7 o# all melanomas + = .7 o# all melanomas

Initially ?at :it! !aBy margins and Initially ?at :it! !aBy margins and
pigmentation pigmentation

Eventually becomes raised and nodular Eventually becomes raised and nodular

36MM gro:s vertically and metastasises early 36MM gro:s vertically and metastasises early

Epidermis appears !yperplasic% :it! atypical Epidermis appears !yperplasic% :it! atypical
melanocytes present on t!e basal aspect2 melanocytes present on t!e basal aspect2

Mitotic 5gures commonly seen Mitotic 5gures commonly seen

Acral Lentiginous
Acral Lentiginous
Malignant Melanoma
Malignant Melanoma


Inasion And
Inasion And
Metastasis
Metastasis

6ate presentation is associated :it!

6ate presentation is associated :it!
:orse prognosis
:orse prognosis

6ate signs o# invasion:

6ate signs o# invasion:
9leeding% ulceration and pain 9leeding% ulceration and pain

Metastasis can occur via lymp!atics or

Metastasis can occur via lymp!atics or
!aematogenous
!aematogenous

Initially regional lymp! nodes

Initially regional lymp! nodes

Distant metastases :
Distant metastases :
6ICER% 68$D% 9A$E% 9R3I$ 6ICER% 68$D% 9A$E% 9R3I$

!isk "actors
!isk "actors

8ltraviolet lig!t &8C3% sun lamps% 8C9)

8ltraviolet lig!t &8C3% sun lamps% 8C9)

Skin type I
Skin type I

0!emicals:
0!emicals:
mercury% lead% coal% tar% aniline dye derivatives mercury% lead% coal% tar% aniline dye derivatives

Radiation:
Radiation:
E rays% E rays% g g rays% radiot!erapy rays% radiot!erapy

Eeroderma pigmentosum
Eeroderma pigmentosum

Increased numbers o# naevi

Increased numbers o# naevi

Positive #amily !istory

Positive #amily !istory

;uman papillomavirus &;PC)

;uman papillomavirus &;PC)

#ltraiolet Lig$t
#ltraiolet Lig$t

8C9 causes:
8C9 causes:

Melanogenesis Melanogenesis

Immediate skin pigmentation by melanin Immediate skin pigmentation by melanin

precursor p!oto=o>idation precursor p!oto=o>idation

Epidermal t!ickening via keratinocyte Epidermal t!ickening via keratinocyte

proli#eration proli#eration

Promotes vitamin D synt!esis Promotes vitamin D synt!esis

8C3 used in sun lamps by around '1=,17

8C3 used in sun lamps by around '1=,17
o# t!e 8F population
o# t!e 8F population

Evidence o# increased risk o# MM in

Evidence o# increased risk o# MM in
subGects :it! dark !air andHor #emales
subGects :it! dark !air andHor #emales

%iagnosis
%iagnosis

;istory
;istory

E>amination using total

E>amination using total
dermatoscopic score &390D)
dermatoscopic score &390D)

Skin biopsy:
Skin biopsy:
S!ave% punc!% incisionalHe>cisional
S!ave% punc!% incisionalHe>cisional

6ymp! node biopsy:

6ymp! node biopsy:
Fine needle aspiration% surgical e>cision
Fine needle aspiration% surgical e>cision

Staging
Staging

Tumour% $ode% Metastasis

Tumour% $ode% Metastasis

0lark<s staging &anatomic e>tent)

0lark<s staging &anatomic e>tent)

9reslo:<s t!ickness &vertical

9reslo:<s t!ickness &vertical
dept!)
dept!)

3merican Ioint 0ommittee on

3merican Ioint 0ommittee on
0ancer &modi5ed T$M)
0ancer &modi5ed T$M)

0linical
0linical

&lark's Staging
&lark's Staging
6evel
6evel
Description
Description
I I 6esions only involve epidermis 6esions only involve epidermis
II II Invasion o# papillary dermis% !as not Invasion o# papillary dermis% !as not
reac!ed papillary=reticular dermal reac!ed papillary=reticular dermal
inter#ace inter#ace
III III Invasion 5lls and e>pands papillary Invasion 5lls and e>pands papillary
dermis% but reticular dermis is not dermis% but reticular dermis is not
penetrated penetrated
IC IC Reticular dermis penetrated% but Reticular dermis penetrated% but
subcutaneous tissue is not subcutaneous tissue is not
C C Subcutaneous tissue invaded via Subcutaneous tissue invaded via
reticular dermis reticular dermis

(reslo)'s T$ickness
(reslo)'s T$ickness
9reslo:<s
T!ickness
T$M Staging
124. mm or less pT'% $1% M1
124- mm to '2.1 mm pT,% $1% M1
'2.' mm to *21 mm pT+% $1% M1
*21 mm and greater
pT*% $1% M1
pT% $'% M1
pT% $,% M1
pT% $% M'

&linical Staging
&linical Staging
Stage Description
I
&6ocal
)
a Primary lesion alone
b
Primary and satellites in a . cm
radius o# t!e primary tumour
c
6ocal recurrence in a . cm radius
o# a resected primary tumour
d
Metastases #ound more t!an . cm
#rom a primary site% but in t!e
primary lymp!atic drainage area
II Regional nodal disease
III Disseminated disease

Treatment
Treatment

Surgical resection o# tumour

Surgical resection o# tumour

MA;S tec!niJue
MA;S tec!niJue

6ymp! node dissection

6ymp! node dissection

0!emot!erapy
0!emot!erapy

Radiot!erapy
Radiot!erapy

Immunot!erapy
Immunot!erapy

Surgical E*cision
Surgical E*cision

3t t!is point in
3t t!is point in
time% t!e only
time% t!e only
maGor eKective
maGor eKective
t!erapy #or
t!erapy #or
malignant
malignant
melanoma
melanoma

E>cision margins
E>cision margins
are important
are important
9reslo:
9reslo:
T!icknes
T!icknes
s
s
E>cision
E>cision
Margin
Margin
Recommend
Recommend
ed
ed
124. mm
124. mm
or less
or less
' cm
' cm
124- to
124- to
*21 mm
*21 mm
, cm
, cm
*21 mm
*21 mm
and
and
greater
greater
+ to . cm
+ to . cm

MO+S Tec$ni,ue
MO+S Tec$ni,ue

Surgeon removes tumour using a

Surgeon removes tumour using a
microscope to map !istology
microscope to map !istology

Stop e>cision :!en !istology is

Stop e>cision :!en !istology is
once again normal
once again normal

T!is spares as muc! skin as

T!is spares as muc! skin as
possible
possible

Lymp$ Node %issection
Lymp$ Node %issection

L!en node kno:n to contain

L!en node kno:n to contain
metastases &t!erapeutic)
metastases &t!erapeutic)

L!en no evidence o# palpable

L!en no evidence o# palpable
masses &immediate)
masses &immediate)

6ymp!oscintigrap!y can !elp to

6ymp!oscintigrap!y can !elp to
identi#y drainage o# a node
identi#y drainage o# a node

&$emot$erapy
&$emot$erapy

Topical or systemic
Topical or systemic

.=?uorouracil% do>orubicin% or
.=?uorouracil% do>orubicin% or
cisplatin
cisplatin

0an delay tumour spread% and can

0an delay tumour spread% and can
sometimes relieve symptoms
sometimes relieve symptoms

0annot cure metastatic melanoma

0annot cure metastatic melanoma

Side eKects include

Side eKects include
immunode5ciency
immunode5ciency

!adiot$erapy
!adiot$erapy

8se !ig!=energy beams to give a

8se !ig!=energy beams to give a
less intense super5cial dose% t!ereby
less intense super5cial dose% t!ereby
sparing t!e surrounding skin% as
sparing t!e surrounding skin% as
melanoma is invariably deep
melanoma is invariably deep

Telet!erapy &e>ternal source) can

Telet!erapy &e>ternal source) can
provide long=term local control and
provide long=term local control and
eKective palliation in melanoma
eKective palliation in melanoma

8sed as an adGuvant
8sed as an adGuvant

Immunot$erapy
Immunot$erapy

Manipulation o# t!e !ost<s o:n

Manipulation o# t!e !ost<s o:n
immune response to:ards tumour
immune response to:ards tumour
cells
cells

Ideas include:
Ideas include:
Immunomodulatory cytokines%
Immunomodulatory cytokines%
autologousHallogeneic
autologousHallogeneic
immunocompetent cells% monoclonal
immunocompetent cells% monoclonal
antibodies% tumour vaccines and
antibodies% tumour vaccines and
inter#eron
inter#eron

Immunot$erapy
Immunot$erapy

$on=speci5c stimulants:
$on=speci5c stimulants:
90D% 0orynebacterium parvum% levimasole 90D% 0orynebacterium parvum% levimasole

Inter#eron
Inter#eron
a
a
can !elp make melanoma
can !elp make melanoma
cells more susceptible to immunologic
cells more susceptible to immunologic
eKector mec!anisms
eKector mec!anisms

Results comparable to drugs like

Results comparable to drugs like
dacarbaBine
dacarbaBine

Inter#eron
Inter#eron
a=,b
a=,b
gives a ,*7
gives a ,*7
improvement in .MSR% and is as cost=
improvement in .MSR% and is as cost=
eKective in !ig! risk patients as ot!er
eKective in !ig! risk patients as ot!er
interventions
interventions

Immunot$erapy
Immunot$erapy

Caccines:
Caccines:

Ciral oncosylates to increase

Ciral oncosylates to increase
antigenicity
antigenicity

Dangliosides to increase antibody

Dangliosides to increase antibody
production
production

&ost -er -atient
&ost -er -atient
0linical
Stage
3ppro>imate 0ost
9ased An
0urrent
E>c!ange
Rates
I N/4+2,+
II N,%'((2+4
III N,4%4/1214
IC N,/%,4,2(4

-reention
-reention

Reduce risk #actor e>posure:

Reduce risk #actor e>posure:

3:areness &TC% lea?ets%

3:areness &TC% lea?ets%
billboards)
billboards)

0overing up &sunscreen%
0overing up &sunscreen%
sunglasses% clot!es)
sunglasses% clot!es)

3voidance &less time in sun)

3voidance &less time in sun)

Screening &possibly #easible)

Screening &possibly #easible)