Malignant melanoma: causes, risk factors, and prevention
Exposure to ultraviolet (UV) light (eg, sunlight, indoor tanning) is the most important risk factor for melanoma.4 UV exposure results in genetic alterations in melanocytes, which in turn lead to malignant transformation.5 Fair-skinned and light-haired persons living in high sun-exposure environments have the greatest risk,5 but malignant melanoma can also affect persons with darker skin (see Sidebar).6 Other risk factors include sunburns, the presence of melanocytic or dysplastic nevi, and a personal history or family history of cutaneous melanoma (see Sidebar).4,5,7 Hereditary gene variants may be a reason for the increased risk among individuals with a family history of melanoma.7-10 Notably, melanoma can also occur on skin that is shielded from sun exposure (see Sidebar).11
Melanoma is one of the more preventable forms of cancer. Counseling in primary care settings about modified behaviors, including decreased intentional tanning, leads to reduced risk of melanoma.12 The United States Preventive Services Task Force (USPSTF) recommends that clinicians counsel patients with fair skin who are 10 to 24 years old to minimize their exposure to sunlight and artificial UV light.13 The ACS recommends4,14
- Avoiding prolonged exposure to midday sun
- Wearing a wide-brimmed hat
- Wearing tightly woven clothing that covers arms and legs
- Wearing sunglasses that block both UVA and UVB rays
- Using a broad-spectrum sunscreen with an SPF of 30 or higher
- Avoiding indoor tanning
Diagnosis
Diagnosis of melanoma combines visual screening, biopsy, and histological examination as discussed below.
Visual screening
Pigmented nevi (moles) are benign proliferations of melanocytes in the skin, and typically do not change in size or disappear over time.15 However, approximately 33% of melanomas are derived from pigmented nevi.15 Visual screening during a total body skin examination (TBSE) is an easy and effective way to detect new or changing moles—patients should be encouraged to examine themselves each month.16,17 A monthly TBSE is especially important for people of color in whom skin cancer, including melanoma, is often diagnosed at a late stage (see Sidebar).6
Characteristic clinical features of pigmented lesions can suggest the presence of melanoma and are represented by the mnemonic “ABCDEs” of melanoma: (A) asymmetry; (B) border irregularity; (C) color variation; (D) diameter >6 mm; and (E) evolving or changing appearance.16,17
Dermatoscopy involves the use of a handheld instrument that provides 10× magnification and illuminates skin such that light reflection from the surface is minimized. The tool is useful for examining pigmented lesions, identifying characteristics suggestive of melanoma, and determining the extent of a biopsy.18,19
Biopsy
While physical characteristics of a pigmented lesion can raise the suspicion of melanoma, definitive diagnosis requires a biopsy of the lesion and examination of the tissue specimen by an experienced dermatopathologist.20 American Academy of Dermatology (AAD) guidelines indicate that a biopsy can be incisional (removing part of the lesion) or excisional (removing the entire lesion).20 For lesions with a high suspicion of being melanoma, AAD recommends an excisional biopsy with 1- to 3-mm margins and sufficient depth to ensure the lesion is not transected.20
Biopsy can be performed by surgical excision, punch excision, or shave removal to a depth below the suspected plane of the lesion.20 Patient age and sex, anatomic location, size of the lesions, and biopsy technique are important information to include with the biopsy tissue specimen.20 Other information, such as dermatoscopic features and photographs, can also help dermatopathologists evaluate the tissue specimen.
Histologic examination of tissue specimen
Melanoma is definitively diagnosed by histopathologic examination of the tissue specimen to assess histologic type and other tumor characteristics.21,22 Tumor thickness (Breslow thickness), ulceration, dermal mitotic rate, peripheral and deep margin status (positive vs negative), anatomic level of invasion (Clark level), and microsatellitosis should be examined and included in the pathology report.20 Other features useful for diagnosis include lymphovascular invasion, neurotropism, regression, T-stage, tumor infiltrating lymphocytes, and vertical growth phase.20
While the aforementioned characteristics may be associated with prognosis and outcome, 3 histologic features are the most important20:
- Maximum Breslow thickness, measured from the granular of the overlying epidermis or base of superficial ulceration to the deepest malignant cells invading the dermis
- Presence or absence of microscopic ulceration, defined as tumor-induced full-thickness loss of epidermis with subjacent dermal tumor and reactive dermal changes
- Mitotic rate: the number of dermal mitoses per mm2; a mitotic rate ≥1 mitosis/mm2 is independently associated with worse disease-specific outcome