• The increasing rate of melanoma diagnoses is
the highest of any cancer in the United States.
• The age-adjusted incidence of invasive
melanoma in the United States increased from
approximately 4 to 18 per 100,000 white
males between 1973 and 1998.73
• The pathogenesis of melanoma is complex
and remains poorly understood to date.
• Melanoma may arise from transformed
• Although nevi (freckles) are benign
melanocytic neoplasms found on the skin of
many people, dysplastic nevi contain a
histologically identifiable focus of atypical
• These lesions are thought to represent an
intermediate stage between benign nevus and
true malignant melanoma.
• Studies demonstrate increased relative risk of
melanoma development based on increasing
numbers of dysplastic nevi found on the
• a strong genetic component has been
• Up to 14% of malignant melanomas occur in a
• family members of those with either
dysplastic nevi or melanoma are at increased
risk for tumor development.
•Once the melanocyte has transformed into the
malignant phenotype, tumor growth occurs
radially in the epidermal plane.
•Even though microinvasion of the dermis may
have occurred, metastases do not occur until
these melanocytes form dermal nests.
• During the subsequent vertical growth phase,
cells develop different cell-surface antigens
and their malignant behavior becomes much
• 90% of melanomas are found on the skin
• the eye and anus are notable sites
• 4% of tumors are discovered as metastases
without any identifiable primary site.
features suggestive of melanoma
pigmented lesion with an irregular border
recent changes in nevus appearance that may
denote malignant transformation.
• 5 to 10% of melanomas are nonpigmented.
• accounts for up to 70% of melanomas
• occur anywhere on the skin except the hands
• typically flat and measure 1 to 2 cm in
diameter at diagnosis.
• a prolonged radial growth phase is
characteristic of these lesions.
• Typically of darker coloration and often raised
• accounts for 15 to 30% of melanomas.
• noted for their lack of radial growth
• all nodular melanomas are in the vertical
growth phase at diagnosis.
• Although considered a more aggressive lesion,
the prognosis for patients with nodular-type
melanomas is similar to that for a patient with
a superficial spreading lesion of the same
• accounts for 4 to 15% of melanomas
• occurs most frequently on the neck, face, and
hands of the elderly.
• tend to be quite large at diagnosis, these
lesions have the best prognosis because
invasive growth occurs late.
• Less than 5% of lentigo maligna are estimated
to evolve into melanoma.
• Least common type
• 2 to 8% of melanomas in white populations.
• this type accounts for 29 to 72% of all
melanomas in dark-skinned people (African
Americans, Asians, and Hispanics).
• Acral lentiginous melanoma most frequently is
encountered on the palms, soles, and
• Most common on the great toe or thumb,
subungual lesions appear as blue-black
discolorations of the posterior nail fold.
• The additional presence of pigmentation in
the proximal or lateral nail folds (Hutchinson's
sign) is diagnostic of subungual melanoma.
• Independent of histologic type and depth of
• lesions of the extremities have a better
prognosis than patients with melanomas of
the head, neck, or trunk (10-year survival rate
of 82% for localized disease of the extremity
compared to a 68% survival rate with a lesion
of the face)
• Lesion ulceration carries a worse prognosis.
The 10-year survival rate for patients with
local disease (stage I) and an ulcerated
melanoma was 50% compared to 78% for the
same stage lesion without ulceration.
• Early studies identified that the incidence of
ulceration increases with increasing thickness,
from 12.5% in melanomas less than 0.75 mm
to 72.5% in melanomas greater than 4.0
mm.74,76 Recent evidence suggests that tumors
ulcerate as the result of increased
• females have an improved survival compared
• Women tend to acquire melanomas in more
favorable anatomic sites
• less likely to contain ulceration.
• After correcting for thickness, age, and
location, females continue to have a higher
survival rate than men (10-year survival rate
of 80% for women vs. 61% for men with stage
• In general, there is no significant difference
between different histologic tumor types in
terms of prognosis, when matched for tumor
thickness, gender, age, or other.
• Nodular melanomas have the same prognosis
as superficial spreading types when lesions
are matched for depth of invasion.
• Lentigo maligna types have a better prognosis
even after correcting for thickness
• acral lentiginous lesions have a worse
• Even though the various types of melanoma
have similar prognoses when controlled for
the other prognostic factors, acral lentiginous
melanoma has a shorter interval to
• Historically, the vertical thickness of the
primary tumor (Breslow thickness) and the
anatomic depth of invasion (Clark level) have
represented the dominant factors in the T
• The T classification of lesions comes from the
original observation by Clark that prognosis is
directly related to the level of invasion of the
skin by the melanoma.
• Whereas Clark used the histologic level [I,
superficial to basement membrane (in situ); II,
papillary dermis; III, papillary/reticular dermal
junction; IV, reticular dermis; and V,
• Breslow modified the approach to obtain a
more reproducible measure of invasion by the
use of an ocular micrometer.
• The lesions were measured from the granular
layer of the epidermis or the base of the ulcer
to the greatest depth of the tumor (I, 0.75 mm
or less; II, 0.76 to 1.5 mm; III, 1.51 to 4.0 mm;
IV, 4.0 mm or more).
• These levels of invasion have been
subsequently modified and incorporated in
the AJCC staging system.
American Joint Committee on
• The most current staging system
• contains the best method of interpreting
clinical information in regard to prognosis of
• The new staging system has largely replaced
the Clark level with another histologic feature,
ulceration, based on analysis of large
databases available to the AJCC Melanoma
• Evidence of tumor in regional LNs is a poor
prognostic sign associated with a steep drop
in survival at 15-year follow-up.
• Positive node status will advance any stage 1
or 2 to stage 3
• Identification of distant metastasis is the
worst prognostic sign and is classified as stage
• Although occasional survival for several years
has been noted, median survival ranges from
2 to 7 months depending on the number and
site of metastases.
How to diagnose
- Physical examination
• Biopsy :• Diagnosis of melanoma typically requires
• A 1-mm margin of normal skin is taken if the
wound can be closed primarily.
• In large lesions incisional biopsy
• Special stains and markers (sp-100), vimentin
• surgical excision is the management of choice.
• Lesions 1 mm or less in thickness can be
treated with a 1-cm margin.
• For lesions 1 mm to 4 mm thick, a 2-cm
margin is recommended.
• Lesions of greater than 4 mm may be treated
with 3-cm margins.
• The surrounding tissue should be removed
down to the fascia to remove all lymphatic
• If the deep fascia is not involved by the tumor,
removing it does not affect recurrence or
survival rates, so the fascia is left intact.
Treatment of regional LNs
• Treatment of regional LNs that do not
obviously contain tumor in patients without
evidence of metastasis is an area of continued
• If < 1 mm depth no LN treatment needed
• With lesions deeper than 4 mm most likely
has distant mets so local LN is not beneficial
no effect on survival (most die of dist mets )
• In patients with intermediate-thickness
tumors (T2 and T3, 1 to 4.0 mm) and no
clinical evidence of nodal or metastatic
disease, the use of prophylactic dissection
(elective LN dissection on clinically negative
nodes) is controversial.
• To date, no prospective, randomized studies
have demonstrated that elective LN dissection
improves survival in patients with
• However, 25 to 50% of LN specimens contain
micrometastases in these cases and
recurrence may be decreased with LN
• Sentinel lymphadenectomy for malignant
melanoma is gaining acceptance
• Once melanoma has spread to a distant site,
median survival is 7 to 8 months and the 5year survival rate is less than 5%.
• Solitary lesions in the brain, GI tract, or skin
that are symptomatic should be excised when
possible. (cure is very rare but asymptomatic
survival prolonged )
• A decision to operate on metastatic lesions
must be made after careful deliberation with
the patient and the treating oncologist.
• Locally recurrent, lymphatic-invading, or
tumors unamenable to surgical excision
present a significant management challenge.
• local disease in lymphatics) develops in 5 to
8% of melanoma patients with a high-risk
primary melanoma (>1.5 mm).
• Hyperthermic ( 42 c) regional perfusion with a
chemotherapeutic agent (e.g., melphalan) is
presently the treatment of choice.
• Difficult to perform
• Associated with complications (neutropenia,
• it does produce a high response rate (greater
• Addition of tumor necrosis factor alpha or
interferon- ϒ with melphalan results in the
regression of more than 90% of cutaneous intransit metastases.
• Use of radiation in under investigation
• High dose per-fraction radiation produces a
better response rate than low dose
• the treatment of choice for patients with
symptomatic multiple brain metastases
• radiation therapy produced measurable
improvement in tumor size, symptomatology,
or performance status in 70% of treated
• Interferon alfa-2b is the only Food and Drug
Administration approved adjuvant treatment
for AJCC stages IIB/III melanoma.
• Side effects were common and frequently
• majority of the patients required modification
of the initial dosage and 24% discontinued
• Immunotherapy also continues to be a field of
• Vaccines have been developed with the hope
of stimulating the body's own immune system
against the tumor.
• Melanoma cells contain a number of distinctly
different cell-surface antigens, and
monoclonal antibodies have been raised
against these antigens.
• Schwartz principles of surgery 9 e