2. MALIGNANT MELANOMA
-Melanoma is a tumor that develops as a result of the
malignant transformation of melanocytes.
-Melanocytes cells are derived from the neural crest.
-Melanomas usually occur on the skin but can arise in
other locations where neural crest cells migrate, such as in
the gastrointestinal tract, eye or brain.
-Melanoma predominantly is an adult disease with a peak
incidence in the 4th
decade and no sex prevalence.
A patient's risk of developing a second primary melanoma
after diagnosis of the first one is 3-5%.
-The incidence is estimated to be rising rapidly by almost
6% per year.
Morbidity and Mortality
-Early diagnosis and treatment before metastasis most
important in management.
While only 5% of skin cancers are melanomas, about two-
thirds of all deaths from skin cancer are due to melanomas
Positive family history in 5-10% of patients
With at least one affected relative, 2.2-fold higher risk
-Blue eyes, fair and/or red hair, pale complexion
-Skin reaction to sunlight - Easily sunburned
3.Benign and/or dysplastic melanocytic nevi - Number
rather than size has better correlation
4.Immunosuppressive states - Transplant patients,
5.Sun exposure during adolescence
➢ High UV-B radiation
➢ Low latitude
➢ Number of blistering sunburns
6.Atypical mole syndrome (formerly termed B-K mole
syndrome, dysplastic nevus syndrome, familial atypical
multiple mole melanoma)
Benign melanocytic nevi are markers of melanoma risk
rather than direct precursors; however, dysplastic nevi are
believed to degenerate over time into melanoma.
Lentigo maligna is believed to be a pre-invasive precursor
of lentigo maligna melanoma, and at least 5% progress to
Patients usually present with skin lesions that have
changed in size, color, contour, or configuration. The
acronym "ABCDE" is the hallmark of international public
awareness campaigns and may be used to remember the
physical characteristics suggestive of malignancy.
ABCDE stands for
A-Asymmetry of shape
C-Color variations (especially red, white, and blue tones
in a brown or black lesion) or deepening of pigmentation
D-Diameter greater than 6 mm(size),or recent increase in
E-Elevated surface, erosions or ulcerations, bleeding
Other symptoms of the lessions
➢ Location in areas of constant trauma or
irritation ,lower limb or the back.
-The appearance of a new pigmented nevus should arouse
suspicion of melanoma.
-About one-third of all melanomas arise from pigmented
-Since the average white adult has 15-20 nevi, a clear idea
of the indications for biopsy or excision should be
developed. Recognition and early excision of atypical
pigmented lesions are potentially lifesaving, since surgery
is the only effective treatment.
Benign /common naevi
-Are usually small, circumscribed, light brown or black,
flat or only slightly elevated, and rarely contain hair. They
are found on all areas f the body, and moles of the
mucous membranes, genitalia, soles, and palms are
usually of this type.
-The nevus cells are located in the epidermis and at the
-Range from small spots to extensive areas covering
much of the body.
-Have variable shape and surface configuration, are
usually brown or black, and often are slightly elevated.
-Nevus cells are confined to the dermis, and the lesions
are basically benign.
Compound nevi have both junctional and intradermal
-Are circumscribed, flat or dome-shaped, bluish-black
lesions, usually on the hands, face, or arms.
-Although benign, they may closely resemble nodular
melanoma and require diagnostic excisional biopsy.
Are larger (5-12 mm) than common nevi.
-They have macular and papular components, are
variegated in color (tan-brown) on a pink base, and have
indistinct, irregular edges.
-Unlike common nevi, dysplastic nevi are most prevalent
on covered body areas, though they can appear anywhere.
Any suspicious lesions should be excised. An accurate
family history should be obtained in such cases, and first-
degree relatives should be examined.
-Occur in about 1% of newborns, and most lesions are
-Along with dysplastic nevi, these lesions are now
classified as precursors of melanoma.
-Lifetime risk of melanoma developing in large
congenital nevi (> 20 cm) is 5-20%, with some increased
risk in smaller lesions as well.
-Prophylactic excision is cosmetically prohibitive in many
cases, and these lesions must be carefully monitored for
Other pigmented lesions, including basal cell carcinomas,
seborrheic keratoses, and actinic keratoses, occasionally
resemble melanoma and require biopsy for diagnosis.
3. ➢ Itching, pain,ulcerate, Bleed, Develop satellites
-Perform biopsy on all lesions suggestive of melanoma in
the thickest part.
-If the resection will not result in a disfiguring defect,
excisional biopsy with a 2-cm skin margin and extending
to the subcutaneous tissue is suggested for lesions less
than 1.5 cm in diameter.
-If the lesion is large or located in an anatomic area where
skin removal would cause disfigurement, an incisional
biopsy may be performed.
-A full-thickness core punch biopsy in the most raised or
irregular area is suggested with the understanding that this
area may not be the thickest area.
The skin is composed of multiple layers. The epidermis is
the most superficial layer, and it contains keratinocytes in
various stages of development. Melanocytes are located in
the deepest layer of the epidermis. A basement membrane
separates the epidermis from the underlying dermis,
which is divided into 2 zones, papillary dermis and
reticular dermis. Subcutaneous tissue is deep to the
Four major types of melanomas exist based on growth
1. Superficial spreading melanoma
2. Nodular melanoma
3. Lentigo maligna melanoma
4. Acral lentiginous melanoma
Other more unusual types include mucosal lentiginous
melanoma, desmoplastic melanoma, and verrucous
1.Superficial spreading melanoma
Commonest up to 70% of melanomas in white population.
➢ Appear singly or in nests along the dermal-
➢ May migrate into the stratum granulosum or
➢ These cells can invade the papillary dermis
with an inflammatory lymphocytic infiltrate.
➢ Usually arise in a preexisting dysplastic nevus.
➢ Typically, this lesion changes slowly over
several months to years.
➢ They are usually flat but may become irregular
and elevated in later stages.
➢ The lesions average 2 cm in diameter with
variegated colors and peripheral notches and/or
They comprise approximately 15-30% of melanoma
➢ Characterized by extensive vertical growth into
the dermis with a minimal radial component.
➢ These tumors typically are blue-black but may
lack pigment in some circumstances.
➢ They are known to arise without a preexisting
lesion. May develop at the site of a preexisting
nevus and rapidly becomes a palpable, elevated,
3..Lentigo maligna melanoma
-4-10% of melanomas. Show dermal and epidermal
changes from sun exposure.
➢ Larger than 3 cm
➢ Flat, tan, and begin as small, freckle-like
➢ They occur in sun-exposed areas (eg, face and
neck of older individuals).
➢ Marked notching of the borders is present.
-Lentigo maligna melanoma usually arises within a
Hutchinson freckle (lentigo maligna).
The histologic appearance
➢ Irregularly shaped hyperchromatic cells that
form spindle-shaped nests.
➢ The epidermis is atrophic
➢ The dermis contains solar elastosis with chronic
4. Acral lentiginous melanoma
This tumor comprises 2-8% of melanomas in whites and
35-60% of melanomas in dark-skinned people.
➢ Occur in dermal-epidermal junction with
microinvasion into the papillary dermis.
➢ The cells have increased melanin granule
production, which fills their dendritic
➢ Occur on the palms of the hands, beneath the
nailbeds, and on the soles of the feet.
➢ They may appear as flat, tan, or brown stains
with irregular borders on the palms and soles
➢ Subungual lesions can be brown or black, with
ulcerations in later stages.
No correlation with a worse prognosis is demonstrated for
these lesions when tumor thickness is considered.
5. Desmoplastic melanoma
-These lesions account for approximately 1% of
melanoma cases; they are fairly rare.
- They demonstrate a tendency for perineural invasion,
especially in the head and neck.
-They have a propensity for higher local recurrence rates
but lower regional metastasis rates.
Classification and staging
Two classification schemes have been developed, based
1.The vertical thickness of the lesion in millimeters
2. The anatomic level of invasion of the layers of skin
Breslow classification scheme is used almost exclusively
now since it more accurately predicts future tumor
The TNM (tumor, node, metastasis) system is used for
4. firm nodule
Breslow classification -Thickness of lesion
Stage 1Thickness of 0.75 mm or less
Stage 2 Thickness of 0.76-1.50 mm
Stage 3 Thickness of 1.51-4.00 mm
Stage 4 Thickness greater than 4.00 mm
Level I - Involves only epidermis (in situ melanoma); no
Level II - Invades papillary dermis
Level III – Papillary-reticular dermis interface
Level IV - Invades reticular dermis
Level V - Invades into subcutaneous tissue
Primary tumor (pT)
pTX - Primary tumor cannot be assessed
pT0 - No evidence of primary tumor
pTis - Melanoma in situ (Clark level [CL] I)
pT1 - Tumor 0.75 mm or less in thickness; invades
papillary dermis (CL II)
pT2 - Tumor 0.76-1.50 mm in thickness and/or invades to
papillary-reticular dermal interface (CL III)
pT3 - Tumor 1.51-4.00 mm in thickness and/or invades
reticular dermis (CL IV)
pT3a - Tumor 1.51-3.00 mm in thickness
pT3b - Tumor 3.01-4.00 mm in thickness
pT4 - Tumor greater than 4.00 mm in thickness and/or
invades subcutaneous tissue (CL V) and/or satellite(s)
within 2 cm of the primary tumor
pT4a - Tumor greater than 4.00 mm in thickness and/or
invades subcutaneous tissue
pT4b - Satellite(s) within 2 cm of primary tumor
Regional lymph nodes (N)
NX - Regional lymph nodes cannot be assessed
N0 - No regional lymph node metastasis
N1 - Metastasis 3 cm or less in greatest dimension in any
regional lymph node
N2 - Metastasis more than 3 cm in greatest dimension in
any regional lymph node(s) and/or in-transit metastasis
N2a - Metastasis more than 3 cm in greatest dimension in
any regional lymph node(s)
N2b - In-transit metastasis
N2c - Both N2a and N2b
Distant metastasis (M)
MX - Distant metastasis cannot be assessed
M0 - No distant metastasis
M1 - Distant metastasis
M1a - Metastasis in skin or subcutaneous tissue or lymph
node(s) beyond the regional lymph nodes
M1b - Visceral metastasis.
-Wide local excision of the primary tumor with 2-cm
Surgical therapy-wide margin excision. If the lesion has
not spread beyond the primary site, it is potentially
For a T1 lesion, 1-cm excision margins are adequate, but
lesions greater than 1 mm require 2-cm margins. Studies
demonstrate no improvement in recurrence or survival
rates with larger margins of resection. Attempt primary
closure and perform skin grafting or flap closure if
necessary. For lesions with a depth greater than 1 mm,
many recommend sentinel lymph node biopsy at the time
of wide local excision (see "Stage II," below).
Perform a 2-cm surgical resection on stage II lesions. No
recurrence or survival advantage exists when 2-cm
margins are compared to wider margins (4-6 cm).
Smaller resection decreases the need for skin grafting and
inpatient hospital stay.
-Perform a complete therapeutic lymphadenectomy on
patients with suspected lymph node metastases based on
physical examination. This consists of excision of all
lymph nodes in the affected regional lymph node basin.
-Consider sentinel lymph node biopsy if no clinically
positive nodes are present. Using blue dye and/or
radioisotope injected at the site of the primary melanoma,
the first-echelon node can be identified within the
regional lymph node basin. Send this sentinel node to the
pathologist for analysis using routine stains,
immunohistochemistry, and even polymerase chain
reaction in some centers.
-If the sentinel node is positive, then predictive
importance exists of regional lymph node metastases;
perform a complete lymph node dissection.
-The correlation is based on the thickness of the primary
tumor. If the sentinel lymph node is negative, a 99%
chance exists that all others are negative. This procedure
is becoming the standard of care for tumors greater than 1
mm in depth.
-Hyperthermic arterial limb perfusion with melphalan for
extremity melanomas has been studied as an adjuvant
therapy. One study found it to be beneficial in that it
produced higher response rates and overall survival rates
than those for surgery alone. Other studies do not
-Adjuvant chemotherapy and/or biological therapy also
are under clinical evaluation. One study demonstrated that
high-dose interferon alfa-2b resulted in prolonged
relapse-free survival and overall survival compared to no
adjuvant therapy. A follow-up study by the same group
demonstrated in preliminary results that high-dose
interferon offered patients a relapse-free survival benefit
over patients who did not receive adjuvant treatment but
not over those who received low-dose interferon.
-Neither high-dose nor low-dose interferon had a
significant overall survival advantage compared to
observation alone. High-dose interferon can be associated
with significant toxic side effects (ie, liver toxicity), and
some patients require dose reduction since it may not be
5. margins remains the first-line therapy.
-. Skin grafting or other tissue-transfer technique may be
necessary to close the defect.
-Perform regional lymph node dissection, since a stage III
melanoma represents nodal disease.
- If the nodal status is unknown, consider a sentinel lymph
node biopsy to determine if the disease is stage I, II, or
-As in stage II disease, a higher rate of treatment failure
exists with wide local excision alone in this group
compared to stages 0 and I. Many clinical trials currently
are exploring similar options as adjuvant therapy.
Advanced metastatic melanoma usually is refractory to
standard therapy; thus, consider these patients for clinical
Some treatments have reported various objective
responses, although they usually are short lived.
Dacarbazine (DTIC) and the nitrosoureas, carmustine
(BCNU) and lomustine (CCNU), produced a 20%
objective response rate.
Response rates for interferon alfa and interleukin-2 range
from 8-22% and 10-20%, respectively. Currently, other
studies in progress are comparing other cytotoxic and
biologic drug regimens.
1) Size of the tumor and the depth of invasion.
Small tumors with minimal invasion (< 0.7 mm)
are usually curable by wide local excision.
2) The prognosis is usually favorable in lentigo
maligna melanoma and in superficial spreading
melanomas without deep invasion. Most
nodular melanomas, particularly if ulcerated
and associated with deep invasion, have a poor
3) Lesions of the extremities have a more
favorable prognosis than those of the trunk, and
4) women with malignant melanoma have better
survival statistics at 5 and 10 years than men.