Malignant Melanoma Skin Cancer

Malignant melanoma is a neoplasm of melanocytes. Although melanoma was once
considered an uncommon disease, the annual incidence and death rate has
increased dramatically over the last few decades.

Frequency
United States
The American Cancer Society has estimated that 68,720 cases of melanoma will be
diagnosed in the United States in 2009 — 39,080 in men and 29,640 in women.

Although melanoma accounts for only approximately 5% of skin cancers, it is
responsible for 3 times as many deaths each year as nonmelanoma skin cancers. The
incidence of melanoma increases by 5-7% yearly, an annual increase second only to
lung cancer in women. While the lifetime risk of developing melanoma in 1935 was
only 1 per 1500, the lifetime risk in 2000 was estimated at 1 per 75.

International
Queensland, Australia has the highest incidence of melanoma in the world with
approximately 57 cases per 100,000 people per year.  Israel also has one of the
highest incidences with approximately 40 cases per 100,000 people annually. The
incidence of malignant melanoma is increasing rapidly worldwide and this increase is
occurring at a faster rate than that of any other cancer except lung cancer in women.
Melanoma is notorious for affecting young and middle-aged people unlike other solid
tumors, which mainly affect older adults.

Pathophysiology
Melanomas originate from melanocytes which reside in the basal layer of the skin and
produce a protective melanin pigment.  The greatest risk of sun exposure–induced
melanoma is associated with acute, intense, and intermittent blistering sunburns.
This risk is different than that of squamous and basal cell skin cancers, which are
associated with prolonged, long-term sun exposure.

Melanoma also may occur in unexposed areas of the skin, including the palms, soles,
and perineum. Certain lesions are considered to be precursor lesions of melanoma,
including the common acquired nevus, dysplastic nevus, congenital nevus, and
cellular blue nevus.

Melanomas have 2 growth phases, radial and vertical. During the radial growth
phase, malignant cells grow in a radial fashion in the epidermis. With time, most
melanomas progress to the vertical growth phase, in which the malignant cells invade
the dermis and develop the ability to metastasize.

Five different forms or histologic types of melanoma exist, as follows:
Superficial spreading melanomas: Approximately 70% of malignant melanomas are the
superficial spreading melanoma (SSM) type and often arise from a pigmented
dysplastic nevus. SSMs typically develop after a long-standing stable nevus changes;
typical changes include ulceration, enlargement, or color changes. A SSM may be
found on any body surface, especially the head, neck, and trunk of males and the
lower extremities of females.

Nodular melanomas: Approximately 10-15% of malignant melanomas and also are
found commonly on all body surfaces, especially the trunk of males. These lesions are
the most symmetrical and uniform of the melanomas and are dark brown or black in
color. The radial growth phase may not be evident in NMs; however, if this phase is
evident, it is short-lived because the tumor advances rapidly to the vertical growth
phase, thus making the NM a high-risk lesion. Approximately 5% of all NMs are
amelanotic melanomas.

Lentigo maligna melanomas: Account for 10-15% of melanomas. They typically are
found on sun-exposed areas (eg, hand, neck). LMMs may have areas of
hypopigmentation and often are quite large. LMMs arise from a lentigo maligna
precursor lesion.

Acral lentiginous melanomas: The only melanomas that have an equal frequency
among blacks and whites. They occur on the palms, soles, and subungual areas.
Subungual melanomas often are mistaken for subungual hematomas (splinter
hemorrhages). Like NM, ALM is extremely aggressive, with rapid progression from the
radial to vertical growth phase.

Mucosal lentiginous melanomas: Develop from the mucosal epithelium that lines the
respiratory, gastrointestinal, and genitourinary tracts. These lesions account for
approximately 3% of the melanomas diagnosed annually and may occur on any
mucosal surface, including the conjunctiva, oral cavity, esophagus, vagina, female
urethra, penis, and anus. Noncutaneous melanomas commonly are diagnosed in
patients of advanced age. MLMs appear to have a more aggressive course than
cutaneous melanomas, although this may be because they commonly are diagnosed
at a later stage of disease than the more readily apparent cutaneous melanomas.

Morbidity/Mortality
Prognosis of a melanoma lesion can be predicted based on the following: the depth
of invasion, presence or absence of ulceration and to nodal status at diagnosis.
Malignant melanomas usually present at 2 extremes: at one end of the spectrum are
patients with small skin lesions that are easily curable by surgical resection and at
the other are patients with widely metastatic disease in whom the therapeutic
options are limited with a median survival of only 6-9 months.

**If detected early, melanoma can be cured with complete, wide, surgical excision.**
Otherwise:
•        Stage IIIC: Patients with any depth lesion, positive ulceration and 1 lymph
node positive for macrometastasis (T1-4b,N1b,M0) or 2-3 nodes positive for
macrometastasis (T1-4b,N2b,M0) or 4 or more metastatic lymph nodes, matted lymph
nodes, or in transit met(s)/satellite(s) have a 5-year survival rate of 24-29%.
•        Stage IV: Melanoma metastatic to skin, subcutaneous tissue, or lymph nodes
with normal LDH (M1a) is associated with a 5-year survival rate of 19%. M1b disease
(metastatic disease to lungs with normal LDH) has a 5-year survival rate of 7%. M1c
disease (metastatic disease to all other visceral organs and normal LDH or any
distant disease with elevated LDH) is associated with a 5-year survival rate of 10%.

Race
Melanoma is more common in whites than in blacks and Asians. The rate of melanoma
in blacks is estimated to be one twentieth that of whites. White people with dark skin
also have a much lower risk of developing melanoma than those with light skin. The
typical patient with melanoma has fair skin and a tendency to sunburn rather than
tan. White people with blond or red hair and profuse freckling appear to be most
prone to melanomas. In Hawaii and the southwestern United States, whites have the
highest incidence, approximately 20-30 cases per 100,000 people per year.

Sex
Melanoma is slightly more common in men than women (1.2:1). Melanoma is the fifth
most common malignancy in men and the sixth most common malignancy in women,
accounting for 5% and 4% of all new cancer cases, respectively.  Women tend to
have lesions that are nonulcerated and thinner than those in men.

Age
Melanoma may occur at any age, although children younger than 10 years rarely
develop a de novo melanoma.
•        The average age at diagnosis is 57 years, and up to 75% of patients are
younger than 70 years.
•        Melanoma is the most common malignancy in women aged 25-29 years and
accounts for more than 7000 deaths annually.
•        It is commonly found in patients younger than 55 years, and it accounts for the
third highest number of lives lost across all cancers.

Clinical History
A family history of irregular, prominent moles is important.  Approximately 10% of all
patients with melanoma have a family history of melanoma. These patients typically
develop melanoma at an earlier age and tend to have multiple dysplastic nevi.

Physical Findings
During a skin examination, assess the total number of typical and atypical nevi
present on the patient's skin. The exam must be conducted on a totally nude patient
in a well lit room, and photos with measurement of the lesions obtained.

The ABCDs for differentiating early melanomas from benign nevi include the following:
o        A - Asymmetry (melanoma lesion more likely to be asymmetric)
o        B - Border irregularity (melanoma more likely to have irregular borders)
o        C - Color (melanoma more likely to be very dark black or blue and have
variation in color than a benign mole, which more often is uniform in color and light
tan or brown)
o        D - Diameter (mole <6 mm in diameter usually benign)

Lymph node examination: If a patient is diagnosed with a melanoma, examine all
lymph node groups. Melanoma may disseminate both through the lymphatics, leading
to involvement of regional lymph nodes, and hematogenously, leading to involvement
of any node basin in the body.

Major Causative Factors
  • Exposure to ultraviolet radiation (UVR) is a critical factor in the development of
    most melanomas.
  • Both ultraviolet A (UVA), wavelength 320-400 nm, and ultraviolet B (UVB), 290-
    320 nm, potentially are carcinogenic and actually may work in concert to induce
    a melanoma.
  • UVR appears to be an effective inducer of melanoma through many
    mechanisms, including suppression of the immune system of the skin, induction
    of melanocyte cell division, free radical production, and damage of melanocyte
    DNA.
  • Interestingly, melanoma does not have a direct relationship with the amount of
    sun exposure because it is more common in white-collar workers than in those
    who work outdoors.
  • The greatest risk for melanoma is associated with acute, intermittent, blistering
    sunburns, especially on areas that occasionally receive sun exposure. LMM is
    an exception to this rule, because it frequently appears on the head and neck
    of older individuals who have a history of long-term sun exposure.
  • Importantly, other factors exist that may predispose an individual to
    melanoma; chemicals and viruses are 2 etiologic agents that also have been
    implicated in the development of melanoma.
  • Greatly elevated risk factors for cutaneous melanoma
  • Changing mole
  • Dysplastic nevi in familial melanoma
  • Greater than 50 nevi, 2 mm or greater in diameter
  • Moderately elevated risk factors for cutaneous melanoma
  • One family member with melanoma
  • Previous history of melanoma
  • Sporadic dysplastic nevi
  • Congenital nevus
  • Slightly elevated risk factors for cutaneous melanoma
  • Immunosuppression
  • Sun sensitivity
  • History of acute, severe, blistering sunburns
  • Freckling

Surgical Treatment
Surgery is the definitive treatment for early stage melanoma. A wide local excision
with sentinel lymph node biopsy and/or elective LND is considered the mainstay of
treatment for patients with primary melanoma.  In patients with solitary or acutely
symptomatic brain metastases, surgical management may alleviate symptoms and
provide local control of disease.

Consultations
If diagnosis of melanoma is made, the patient should be referred to an oncologist
after definitive surgery is performed.

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