Rizwan Haq, MD, PhD, and F. Stephen Hodi, MD
Melanoma is the sixth most common cancer in
the United States and the leading cause of deaths
among all cutaneous malignancies.
1,2 In 2012, it
was estimated that approximately 75,000 individuals were diagnosed with melanoma and more than
9000 died. The incidence of melanoma is rising
the fastest among all major malignancies,
3 and the
lifetime risk of melanoma among men and women
now exceeds 1 in 68, as compared with 1:1500 in
1930.4 The incidence of melanoma is predicted to
continue increasing, and there has been no corresponding decrease in mortality.
3 This case-based
review summarizes the etiology, risk factors, clinical presentation, and management of cutaneous
melanomas, which comprise the majority of melanoma cases. The biology and management for
other noncutaneous melanomas (such as mucosal
or ocular melanomas) are beyond the scope of this
ETIOLOGY AND RISK FACTORS
Melanoma has been proposed to arise through
a stepwise progression of molecular lesions in a
5 Nevi arising from proliferating me-
lanocytes acquire sequential genetic lesions that
lead to dysplasia, invasion, and ultimately metas-
tasis. This process is influenced by both environ-
mental and genetic factors. Although it has not
been possible to prove experimentally, exposure to
ultraviolet light (sunlight) has been strongly impli-
cated as an important causative factor,
6 and ultra-
violet signature mutations are commonly detected
in the genomes of melanoma.
7 The incidence of
melanoma correlates with geographic latitude, with
higher incidence close to the equator and progres-
sively lower incidence toward the poles.
8, 9 Ultra-
violet B (wavelengths 290–320 nm) is most closely
associated with melanoma, although ultraviolet
A wavelength exposure in tanning salons also
correlates with melanoma risk.
10–12 The pattern of
exposure to ultraviolet light also appears to be im-
portant, as intermittent, intense exposure in child-
hood carries more risk than chronic, low-level of
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2 Hospital Physician Board Review Manual