Melanoma (malignant melanoma)

Cutaneous Melanoma
• also known as malignant melanoma, is a
type of cancer that develops from the
pigment-containing cells known as
melanocytes.

Classification Of Melanoma
I : De novo melanoma
A. Melanoma in situ (MIS)
B. Lentigo maligna melanoma (LMM)
C. Superficial spreading melanoma (SSM)
D. Nodular melanoma (NM)
E. Acral-lentiginous melanoma (ALM)
F. Melanoma of the mucous membranes
G. Desmoplastic melanoma

II Melanoma arising from precursors
A. Melanoma arising in dysplastic
nevomelanocytic nevi
B. Melanoma arising in congenital
nevomelanocytic nevi
C. Melanoma arising in common NMN

Etiology And Pathogenesis
• The etiology and pathogenesis of
cutaneous melanoma are unknown.
• Epidemiologic studies demonstrate a role
for genetic predisposition and sun
exposure in melanoma development.
• The major genes involved in melanoma
development reside on chromosome 9p21.

Etiology
• UVR, mostly of the UVB spectrum (290–320 nm)
that induces mutations in suppressor genes. The
propensity for multiple BCC may be inherited.
Associated with mutations in the PTCH gene in
many cases.

Predisposing Factors
Genetic markers (CDKN2a mutation)
Skin type I/II
Family history of dysplastic nevi or
melanoma
Personal history of melanoma
Ultraviolet irradiation, particularly sunburns
during childhood and intermittent burning
exposures

Predisposing Factors cont..
Number (>50) and size (>5 mm) of
melanocytic nevi
Congenital nevi
Number of dysplastic nevi (>5)
Dysplastic melanocytic nevus syndrome
Immune suppression (debatable)

Data And Facts
• Melanoma represents 5% of all cancers by
incidence in males and 6% in females.
• Most frequent sites
Whites
• Male: back, upper extremities.
• Female: back, lower legs.
Blacks and Asians: soles, mucous
membranes, palms, nail beds.

Melanoma Recognition
• Six Signs of Malignant Melanoma
(ABCDE Rule):
A- Asymmetry in shape—one-half unlike the other
half.
B- Border is irregular—edges irregularly
scalloped, notched, sharply defined.
C- Color is not uniform; mottled—haphazard
display of colors; all shades of brown, black, gray,
red, and white.

D- Diameter is usually large.
E- Elevation is almost always present and
is irregular—surface distortion is assessed
by side-lighting. others use E for
Enlargement— a history of an increase in
the size of lesion is one of the most
important signs of malignant melanoma.

Clinical Manifestation
• The clinical characteristics of the four
major types of melanoma are summarized
in Table ‫ليجوه‬ .
• Also discussed in this section are
melanoma in situ and desmoplastic
melanoma

Melanoma In Situ (MIS)
• The clinical features of MIS are not always
clearly presented.
the term is used when melanoma cells are
• confined to the epidermis, above the basement
membrane;
• basilar melanocytic atypia, hyperplasia, and
spread either occur in single-file alignment along
the basal membrane or are distributed
throughout the epidermis (pagetoid spread)

Such lesions
1- are flat, within the level of the skin, and
thus a macule

2- or a macule with barely perceptible
elevation with irregular borders and marked
variegation of color: brown, dark brown, and black
or reddish tones but without gray or blue

• The clinical correlations of MIS are lentigo
maligna and flat superficial spreading
melanoma and these are discussed in
the respective sections below.

Lentigo Maligna Melanoma
(LMM)
• The clinical features of MIS are not always
clearly presented.
the term is used when melanoma cells are
• confined to the epidermis, above the basement
membrane;
• basilar melanocytic atypia, hyperplasia, and
spread either occur in single-file alignment along
the basal membrane or are distributed
throughout the epidermis (pagetoid spread)

Epidemiology
• Age of Onset: Median age 65.
• Sex Equal incidence in males and
females.
• Race Rare in brown- (e.g., Asians, East
• Indians) and extremely rare in black
skinned (African Americans and Africans)
persons.
• Highest incidence in whites and skin
phototypes I, II, and III.

Epidemiology
• Incidence 5% of primary cutaneous
melanomas.
• Predisposing Factors:
Same factors as in sun induced non
melanoma skin cancer: older population,
outdoor occupations (farmers, sailors,
construction workers).

Pathogenesis
• In contrast to SSM and NM, which appear
to be related to intermittent high-intensity
sun exposure and occur on the
intermittently exposed areas (back and
legs) of young or middle-aged adults, LM
and LMM occur on the face, neck, and
dorsa of the forearms or hands

Pathogenesis
; furthermore, LM and LMM occur almost
always in older persons with evidence of
heavily sun damaged skin (dermatoheliosis).
The evolution of the lesion most clearly
reveals the transition from the radial to the
vertical growth phase and from a clinically
recognizable MIS to invasive melanoma

• LMM very slowly evolves from LM over a
period of several years, sometimes up to
20 years. There is practically always a
background of dermatoheliosis.

Skin Lesions Lentigo Maligna
• Uniformly flat, macule ; 0.5 cm or larger,
up to 20 cm.

• Lentigo maligna A very large lentigo maligna on the right
cheek with the typical variegation in color (tan, brown, black)
and highly irregular shape. The lesion is flat, macular, and
thus represents in situ melanoma.

• The classically macular lentigo maligna is highly
irregular in shape and variegated in color. However,
there is a bluish component and a large pink nodule in
the infraorbital region, indicating a switch from the radial
to the vertical growth phase and thus invasiveness: the
lesion is now called lentigo maligna melanoma.

• Lentigo Maligna Melanoma The clinical change
that indicates the transition of LM to LMM is the
appearance of variegated red, white, and blue
and of papules, plaques, or nodules

Thus LMM is the same as LM plus (1)
gray areas (indicate focal regression), and
blue areas [indicating dermal pigment
(melanocytes or melanin)], and
• (2) papules or nodules, which may be
blue, black, or pink

Distribution
• Single isolated lesion on the sun exposed
areas:
 Forehead,
 Nose,
 Cheeks,
 Neck,
 Forearms,
 And dorsa of hands;
 Rarely on lower legs.

Laboratory Examination
• Dermatopathology : LM shows increased
numbers of atypical melanocytes distributed in a
single layer along the basal layer and above the
basement membrane of an epidermis that
shows elongation of rete ridges.

• Lentigo maligna melanoma (LMM).
Extending from the epidermis into the
dermis are numerous elongated
melanocytes.
In LMM, these cells
are frequently
spindle shaped.

• Atypical melanocytes are usually singly
dispersed but may also aggregate to small
nests and extend into the hair follicles,
reaching the middermis, even in the
preinvasive stage of LM. In LMM, they
invade the dermis (vertical growth phase)
and expand into the deeper tissues

• Stage 0 melanoma in situ.

Stage I melanoma
• . In stage IA, the tumor is not more than 1
millimeter thick, with no ulceration (break
in the skin). In stage IB, the tumor is either
not more than 1 millimeter thick, with
ulceration, OR more than 1 but not more
than 2 millimeters thick, with no ulceration.
Skin thickness is different on different
parts of the body.

Stage II melanoma
• In stage IIA, the tumor is either more than 1 but
not more than 2 millimeters thick, with ulceration
(break in the skin), OR it is more than 2 but not
more than 4 millimeters thick, with no ulceration.
In stage IIB, the tumor is either more than 2 but
not more than 4 millimeters thick, with ulceration,
OR it is more than 4 millimeters thick, with no
ulceration. In stage IIC, the tumor is more than 4
millimeters thick, with ulceration. Skin thickness
is different on different parts of the body.

Stage III melanoma
The tumor may be any thickness, with or without
ulceration (a break in the skin), and (a) cancer has
spread to one or more lymph nodes; (b) lymph
nodes with cancer may be joined together
(matted); (c) cancer may be in a lymph vessel
between the primary tumor and nearby lymph
nodes; and/or (d) very small tumors may be found
on or under the skin, not more than 2 centimeters
away from the primary tumor.

Stage IV melanoma. The cancer has
spread to other parts of the body,
such as the brain, lung, liver, lymph
nodes, small intestine, and bone.

Stage IV melanoma
• In stage IV, the cancer has spread to other
places in the body, such as the lung, liver,
brain, bone, soft tissue, or gastrointestinal
(GI) tract. Cancer may have spread to
places in the skin far away from where it
first started.

Management
1. Very early LM lesions: Imiquimod.
2. Excise with 1-cm beyond the clinically
visible lesion where possible and provided
the flat component does not involve a major
organ. Use of Wood lamp and dermoscopy
help in defining borders.
3. Sentinel node to be done in lesions >1.0
mm in terms of thickness.

Superficial Spreading
Melanoma
• Superficial spreading melanoma (SSM) is the
most common melanoma (70%) type in persons
with white skin.

Epidemiology
• Age of Onset 30 to 50 (median, 37) years
of age.
• Sex Slightly higher incidence in females.
• Race In world surveys, white-skinned
persons overwhelmingly predominate.

Epidemiology
• Incidence SSM constitutes 70% of all
melanomas arising in white persons.
• Predisposing Factors:
• In order of importance these are presence
of precursor lesions , family history,
light skin color (skin phototypes I and II);
and sunburns,

Skin Lesions
• SSM is the lesion to which the ABCDE
rule .
• Initially a very flat plaque 5–12 mm or
smaller

• Dark brown, black, with admixture of pink,
gray, and blue-gray hues—with marked
variegation and a haphazard pattern.
White areas indicate regressed portions

• An SSM is thus a flat plaque with all
shades of brown to black plus the
American flag or the tricolore (red, blue,
white)

• As the vertical growth phase progresses,
nodules appear; eventually erosions and
even superficial ulceration develop

Distribution
• Back (males and females); legs (females,
between knees and ankles); anterior trunk
and legs in males lesions on covered
areas, e.g., buttocks, lower abdomen

• Dermatopathology
• Malignant melanocytes expand in a
pagetoid pattern Superficial papillary body
of the dermis—the radial growth phase.
• In the vertical growth phase, presenting
clinically as small nodules, they expand
further into the reticular dermis

Course And Prognosis
• Left untreated, SSM develops deep
invasion (vertical growth) over months to
years

Diagnosis
• Clinically according to the ABCDE rule,
verified by dermoscopy.

Nodular Melanoma
Epidemiology
• Age of Onset Middle life.
• Sex Equal incidence in males and females
• Race NM occurs in all races,
• Incidence NM constitutes 15%

Pathogenesis
• Both SSM and NM occur in approximately
the same sites (upper back in males, lower
legs in females),

• Skin Lesions Uniformly elevated “blueberrylike”
nodule or ulcerated or “thick” plaque; may
become polypoid. Uniformly dark blue, black, or
“thundercloud”gray Early lesions are 1–3 cm in
size but may grow much larger if undetected.
Oval or round, usually with smooth, not irregular,
borders, as in all other types of melanoma.
Sharply defined, may be pedunculated

Laboratory Examinations
• Dermatopathology Malignant
melanocytes,which appear as epithelioid,
spindle, or small atypical cells, show little
lateral (radial) growth within and below the
epidermis and invade vertically into the
dermis and underlying subcutaneous fat

• Serology Serum levels of S-100 beta and
melanoma-inhibiting activity (MIA), S-
cysteinyldopa, and lactate dehydrogenase
(LDH) levels are markers for advanced
melanoma patie

Differential Diagnosis
• Blue/Black Papule/Nodule NM can be
confusedwith hemangioma (long history)
and pyogenic granuloma (short history—
weeks) sometimes almost
indistinguishable from pigmented basal
cell carcinoma

Desmoplastic Melanoma (Dm)
• The term desmoplasia refers to connective
tissue proliferation and, when applied to
malignant melanoma, describes (1) a dermal
fibroblastic component of melanoma with only
minimal melanocytic proliferation at the dermal-
epidermal junction; (2) nerve-centered
superficial malignant melanoma with or without
an atypical intraepidermal melanocytic
component; or (3) other lesions in which the
tumor appears to arise in lentigo maligna or,
rarely, in acral lentiginous melanoma or
superficial spreading melanoma

• DM may be a variant of LMM in that most
lesions occur on the head and neck in
patients with dermatoheliosis. DM is more
likely to recur locally and metastasize than
LMM, however. DM is rare and occurs
more frequently in women and persons
>55 years old

• At diagnosis DM lesions have been
present from months to years. DM is
asymptomatic, usually not pigmented and
is therefore overlooked by the patient.
Early lesions may appear as variegated
lentiginous macules or plaques, at times
with small blue-gray specks of color .
• Later lesions may appear as dermal
nodules, and although they commonly lack
any melanin

• There are mixed views about the
prognosis of DM. In one series,
approximately 50% of patients
experienced a local recurrence after
primary excision of DM, usually within 3
years of excision; some patients
experienced multiple recurrences. Lymph
node metastasis occurs less often than
local recurrence. In one series, 20%
developed metastases, and DM was
regarded as a more aggressive tumor than
LMM.

Acral Lentiginous Melanoma
Epidemiology
• Age of Onset Median age is 65.
• Incidence 7 to 9% of all melanomas; in
whites, 2 to 8%.
• Sex Male:female ratio, 3:1.
• Race ALM is the principal melanoma in
the Japanese (50–70%) and in American
and sub- Saharan African blacks.

Skin Lesions
• Acral and Palm/Sole Macular or slightly
raised lesion in the radial growth phase
• Subungual Subungual macule beginning
at the nail matrix nail bed and nail plate.
Papules, nodules, and destruction of the
nail plate may occur in the vertical growth
phase

• Dermatopathology intense lymphocytic
• inflammation at the dermal-epidermal
junction. Characteristic large melanocytes
along the basal cell layer may extend as
large nests into the dermis, along eccrine
ducts.

Prognosis
• Five-year survival rates are <50%. The
subungual type of ALM has a better 5-year
survival rate (80%) than does the volar
type,

Management
• Subungual ALM and volar-type ALM:
amputation [toe(s), finger(s)]; volar and
plantar ALM: wide excision with split skin
grafting. Sentinel lymph node procedure
necessary in most cases

Amelanotic Melanoma
• All types of melanoma can be amelanotic.
Since they don't have the characteristic
pigment marker they are a diagnostic
challenge often there are pigmented clones
in the tumor, which reveal its nature as a
melanoma In most cases only biopsy will
reveal the correct diagnosis

Malignant Melanoma Of The
Mucosa
• Malignant melanomas arising in the
mucosal epithelial lining of the respiratory
tract and gastrointestinal and genitourinary
tracts are very rare, with an annual
incidence of 0.15% per 100,000
individuals.

• Major sites of the mucosal melanomas are
the vulva and vagina (45%) and the nasal
and oral cavity (43%).

Metastatic Melanoma
• Metastatic melanoma occurs in 15–26% of
stage I
• stage II melanoma .
• The spread of disease from the primary
site usually occurs in a stepwise
sequence: primary melanoma→ regional
metastasis → distant metastasis.

• Distant metastasis can occur, skipping the
regional lymph nodes and indicating
hematogenous spread.
• Distant metastases occur anywhere but
usually in the following organs: lungs (18–
36%), liver (14–29%), brain (12–20%),
bone (11–17%), and intestines (1–7%).

• Widespread metastasis can also lead to
singlem metastatic melanoma cell
lodgement in all organs with melanosis of
the skin ,mucous membranes, liver,
kidney, heart muscle and other tissues.

• Melanoma may have a late recurrence
(≥10 years). The usual time is 14 years,
but there have been “very late”
recurrences (>15 years) Patients with a
solitary metastasis confined to the
subcutaneous, nonregional lymph nodes
or lung are most likely to benefit from
surgical intervention.

Staging Of Melanoma
• Staging of melanoma depends on its TNM
Classification (primary tumor, regional n
odes, m etastases.
• Clinical staging of melanoma
differentiates between local, regional, and
distant disease and is based on
microstaging of the melanoma and clinical
and imaging evaluation for metastases.

• Pathologic staging consists of
microstaging of the primary tumor and
pathologic evaluation of regional lymph
nodes . Staging of melanoma is strongly
correlated with survival.

Prognosis Of Melanoma
• Prognosis of melanoma can be either
excellent or grave, depending on whether
the tumor is diagnosed early or late, when
regional or distant metastases have
occurred This emphasizes the importance
of early diagnosis, of questioning patients
for melanoma

Management Of Melanoma
• The only curative treatment of melanoma
is early surgical excision.

• SOURCE: From FITZPATRICK’S COLOR ATLAS
AND SYNOPSIS OF CLINICAL DERMATOLOGY
SIXTH EDITION

Melanoma (malignant melanoma)

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