2. Introduction
neoplasm of epidermal melanocytes
more biologically unpredictable and deadly of
all human neoplasms
third most common cancer of the skin (basal
and squamous cell carcinomas are more
prevalent)
3%
Results in over 83% of all deaths due to skin
cancer in the United States
increasing in incidence
The frequency of its occurrence is closely
associated with the constitutive color of the
skin, and depends on the geographical zone.
3. Introduction
among dark skinned ethnic groups is 1
per 100,000 per year or less
affecting mainly the palms, soles, and
mucous membranes
light-skinned Caucasians up to 50 and
higher in some areas of the world
Cutaneous malignant melanoma is the
most rapidly increasing cancer in whites
sunlight is an important etiologic factor in
cutaneous melanoma
4. Melanomas may develop in or near a
previously existing precursor lesion or in
healthy-appearing skin
A malignant melanoma developing in
healthy skin is said to arise de novo,
without evidence of a precursor lesion
Certain lesions are considered to be
precursor lesions of melanoma, including
the common acquired nevus, dysplastic
nevus, congenital nevus, and cellular
blue nevus
5. Etiology
Environmental
1. Sun exposure
2. Artificial UV sources
3. Socioeconomic status
4. Fair skin, freckles, red hair
5. Number of melanocytic nevi
ETIOLOGY
Genetic
1. Familial melanoma
2. Xeroderma pigmentosum
6. Environmental Factors
Sun exposure
The highest incidence of melanoma -
areas with long hours of sunlight
throughout most of the year
lower risk for melanoma among people
who resided in a low ultraviolet
environment in childhood compared with
those who resided in a high UV
environment
Recreational activity leading to sunburns
in adulthood, such as sailing, has also
been incriminated as an etiological factor
7. Environmental Factors
Artificial UV sources
melanoma risk and tanning lamp use
have demonstrated a
positive relation
longer wave artificial UVA may play a
part in the etiology of melanoma in
addition to exposure to natural sunlight
The association of melanoma with PUVA
(combination of psoralen (P) and long
wave ultraviolet radiation (UVA)) therapy
has also been reported
8. Environmental Factors
Socioeconomic status
melanoma is more prevalent in those
of high socioeconomic status
An explanation - better afford holidays
in areas of high UV intensity, as well
as expensive outdoor hobbies like
sailing
9. Environmental Factors
Fair skin, freckles, red hair
increase the risk of melanoma
Number of melanocytic nevi.
The total number of melanocytic nevi,
dysplastic or bland, has been reported
by several groups as a strong risk
factor
10. Genetic Factors
Familial melanoma
2-5% of melanoma patients - positive
family history of melanoma in at least
one first degree relative
In approximately 30% of melanoma
patients abnormalities on
chromosome 9p21 are seen
11. Genetic Factors
Xeroderma pigmentosum
In this genetically determined disorder,
defective DNA repair mechanisms
lead to excessive chronic UV damage
and subsequent development of
different sun-related skin tumors,
including melanoma, in sun-exposed
areas
12. Risk Factors for oral mucosal
melanomas
unknown
no apparent relationship to chemical, thermal,
or physical events (e.g. smoking, alcohol
intake, poor oral hygiene, irritation from teeth,
dentures, or other oral appliances) to which
the oral mucosa is constantly exposed
Although benign, intraoral melanocytic
proliferations (nevi) occur and are potential
sources of some oral melanomas; the
sequence of events is poorly understood in
the oral cavity
Currently, most oral melanomas are thought
to arise de novo
13. Growth of melanoma
In 1975, Clark and his coworkers –
interesting concept - developmental
biology of cutaneous melanoma
They documented two phases in the
growth of melanoma:
1. the radial-growth phase and
2. the vertical-growth phase
14. Radial-growth phase
initial phase of growth
may last many years
confined to the epidermis
Neoplastic cells are shed with
normally maturing epithelial cells
some neoplastic cells may actually
penetrate the basement membrane,
they are destroyed by a host-cell
immunologic response
15. Vertical-growth phase
begins when neoplastic cells populate
the underlying dermis.
Because of increased virulence of the
neoplastic cells, a decreased host-cell
response, or a combination of both
Metastasis is possible
not all melanomas have both radial- and
vertical-growth phases
Nodular melanoma (q.v.) exists only in
the vertical-growth phase.
18. Classification
Cutaneous melanoma has been
classified into a number of types
1. superficial
2. spreading melanoma
3. nodular melanoma
4. lentigo maligna
5. melanoma (Hutchinson’s freckle)
6. acral lentiginous melanoma
19. Clinical Features
Superficial spreading melanoma
most common
65% of cutaneous melanomas
exists in a radial-growth phase (called
premalignant melanosis or pagetoid melanoma in
situ)
tan, brown, black or admixed lesion on sun-
exposed skin, especially the back
occurs on the skin of the head and neck, chest
and abdomen and the extremities
The radial-growth phase may last for several
months to several years
The vertical-growth phase - an increase in size,
change in color, nodularity and, at times,
ulceration
20.
21. Clinical Features
Nodular melanoma
approximately 13%
no clinically recognizable radial-growth
phase, existing solely in a vertical growth
phase
sharply delineated nodule with varying
degrees of pigmentation
Pink (amelanotic melanoma) or black
Predilection for occurrence on the skin of the
back and head and neck skin of men
In other cutaneous sites, there is an even
gender distribution
22. Clinical Features
Lentigo maligna melanoma
approximately 10%
radial-growth phase which is known as lentigo
maligna or melanotic freckle of Hutchinson
macular lesion on the malar skin of middle-aged
and elderly Caucasians
more often in women than in men
An average age of 58 years in men and 55 in
women
median age was 70 years
lesion can remain in the radial-growth phase for
years
not only on the skin but also in the eye and on
mucous membranes
23.
24. Clinical Features
Acral lentiginous melanomas
palms and soles, as well as on toes and
fingers
10% of cases in whites
50% of all melanomas on Black and Asian
skin
macular, lentiginous pigmented area around
a nodule
Mechanical stress - erosion and ulceration
Subungual melanomas - pigmentations of the
nail bed
extremely aggressive, with rapid progression
from the radial to vertical growth phase
25. Clinical Features
Mucosal lentiginous melanomas
develop from the mucosal epithelium that
lines the respiratory, gastrointestinal, and
genitourinary systems
Approximately 3% of the melanomas
may occur on any mucosal surface,
including the conjunctiva, oral cavity,
esophagus, vagina, female urethra,
penis, and anus
Noncutaneous melanomas - advanced
age
aggressive course
26. Clinical Features
Amelanotic melanoma
erythematous or pink, sometimes
eroded, nodule
often confused for other tumors
only the histological examination
provides the right diagnosis
27. ABCDE-rule
The following criteria aid clinical diagnosis of
melanoma (ABCDE-rule):
Asymmetry—in which one half does not
match the other half
Border irregularity—with blurred, notched, or
ragged edges
Color irregularity—pigmentation is not
uniform. Brown black, tan, red, white, and
blue—can all appear in a melanoma
Diameter—greater than 6 mm. Growth in
itself is also a sign
Elevation—a raised surface can also be a
sign
30. Oral Manifestation
Uncommon neoplasm of the oral
mucosa
0.2–8%
melanoma of the oral mucosa - one of
the most common sites for the
neoplasm in Japanese
Melanomas in Blacks are seldom
found in the skin yet occur on mucous
membranes and on the plantar skin
31.
32.
33.
34.
35. Oral Manifestation
Primary oral melanoma is nearly twice as
common in men as in women
55 years (40 and 70 years)
definite predilection for the palate and maxillary
gingiva/alveolar ridge
also recorded on the buccal mucosa, mandibular
gingiva, tongue, lips and floor of the mouth
deeply pigmented area
At times ulcerated and hemorrhagic
tends to increase progressively in size
Amelanotic melanoma accounts for 5–35% of
oral melanomas which appear as a white,
mucosa-colored, or red mass
36. Oral Manifestation
focal pigmentation precedes before
the development of the actual
neoplasm
the appearance of melanin
pigmentation in the mouth and its
increase in size and in depth of color
should be viewed seriously
melanomas of the oral mucosa - can
exist in radial- and vertical-growth
phases
39. H/P
malignant cells - nest or cluster in groups in
an organoid fashion
however, single cells can predominate
Cells are round or polygonal
melanoma cells have large nuclei, often with
prominent nucleoli, and show nuclear
pseudoinclusions due to nuclear membrane
irregularity
The abundant cytoplasm may be uniformly
eosinophilic or optically clear
Occasionally, the cells become spindled or
neurotized in areas (interpreted as a more
aggressive feature)
41. H/P
SUPERFICIAL SPREADING MELANOMA
Malignant cells - confined to the epithelium - no
host cell response in the underlying connective
tissue
If Melanocytes penetrate basement membrane, a
florid host cell response of lymphocytes develops
Macrophages and melanophages may be
present
The tumor cells are often destroyed by this
cellular response
The vertical-growth phase is characterized by the
proliferation of malignant epithelioid melanocytes
in the underlying connective tissues
The cells may be arranged singly or in clusters
Melanin pigment is usually scanty
42.
43.
44. H/P
Nodular melanoma also is characterized
by large, epithelioid
melanocytes within the connective
tissue. However, small
ovoid and spindle-shaped cells may be
present. Melanin
pigment is usually but not invariably
present. The tumor
cells may invade and ulcerate the
overlying epithelium and
penetrate the deep soft tissues
45.
46. H/P
Lentigo maligna (melanotic freckle of Hutchinson)
Well defined histologic features
increased numbers of atypical melanocytes within the
basal epithelial layer
Epithelium - generally atrophic
dermal collagen shows the effects of sun-damage
(basophilic degeneration)
If skin appendages are present, they are often involved
with atypical melanocytes as well.
In time, cords and nests of atypical melanocytes may
be evident
characterized by invasive spindle-shaped cells into the
underlying dermis
A lympho-histiocytic infiltrate is usually present
47. H/P
Acral-lentiginous Melanoma
histologically similar to lentigo maligna
melanoma
salient histologic features are:
A lentiginous radial-growth phase
A deep vertical-growth phase composed
predominantly of spindle-shaped cells
Psoriasiform epidermal hyperplasia
An intense host-cell response
A prominent desmoplasia associated
with the vertical growth phase
48.
49. H/P
Less common histologic variants of
melanoma
1. Desmoplastic
2. Neurotropic
3. spindle cell and
4. balloon cell melanomas
50. Investigation
The lymph node metastasis is
identified – lympho-scintigraphy and a
radioactive tracer (technetium labeled
sulfur colloid or human serum
albumin)
51. Investigation
immunohistochemical stains – not necessary for
diagnosis
performed for confirmation
Both S-100 and homatropine methylbromide (HMB45)
stains are positive in melanoma
The S-100 is highly sensitive, although not specific, for
melanoma
HMB45 is highly specific and moderately sensitive for
melanoma.
Both stains, in concert, can be useful in diagnosing
poorly differentiated melanomas
Vimentin is positive in most cases
Recently, microphthalmic transcription factor,
tyrosinase, and melano A immunostains have been
used to highlight melanocytes
53. Treatment and Prognosis
The treatment of cutaneous malignant
melanoma is surgical excision
regional lymph node dissection is indicated
when nodes are involved
tumors greater than 0.75 millimeters in
thickness and located in the so-called BANS
(back, arm, neck and scalp) sites have a
greater tendency to metastasize
On the other hand, melanomas of the skin of
the face have a much more favorable
prognosis
Chemotherapy, immunotherapy and radiation
therapy have been used in the treatment of
cutaneous melanoma
54. Treatment and Prognosis
The treatment of oral melanoma –
surgical excision
Jaw resection and lymph node
dissection - in cases involving bone
and regional lymph nodes
55. Treatment and Prognosis
both clinical and histologic factors which
are of great prognostic significance in
cutaneous melanomas
According to McGovern, clinical features
with prognostic significance are the
gender and age of the patient and the
site of the lesion
Women have a much better survival rate
up to the age of 50 years and then the
rate declines
56. Treatment and Prognosis
Histologic features -of prognostic
significance - histologic type and
depth of invasion
Nodular melanoma and superficial
spreading melanoma have much
poorer prognosis than lentigo maligna
melanoma
tumors less than 0.75 mm in thickness
rarely metastasize or cause death,
regardless of the location on skin
57. Treatment and Prognosis
Unfortunately, oral mucosal
melanomas have a far worse
prognosis than cutaneous melanomas
the five-year survival rate for such
tumors is approximately 7%
58. Treatment and Prognosis
The level of tumor invasion is another
important indicator of the prognosis of
MM
The Clark system is generally used
to grade tumor invasion based on the
deepest histologic cutaneous structure
the tumor infiltrates