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- Melanoma is a tumor arising from malignant transformation of pigment-containing cells called melanocytes, which are found in the stratum basale of the epidermis.
- Most arise in the skin but may also present as a primary lesion in any tissue: ocular (uvea), GI, GU, lymph node, paranasal sinuses, nasal cavity, anorectal mucosa, and leptomeninges.
- Extracutaneous sites have an adverse prognosis.
- Metastatic spread to any site in the body
- Types of cutaneous melanoma include (1):
- Superficial-spreading melanoma: 50–80% of cases; occurs in sun-exposed areas (trunk, back, and extremities); most ~6 mm diameter at diagnosis; when seen in younger patients, presents as a flat, slow growing, irregularly bordered lesion
- Nodular: 20–30% of cases; present in older patients; tendency to ulcerate and hemorrhage; most commonly thick and pigmented
- Lentigo maligna (subtype of melanoma in situ): slowest growing; older population; occurs in sun-exposed areas (head, neck, forearms). Lentigo maligna melanoma (LMM) is its invasive counterpart seen in (5–15% of cases); it is most commonly seen in elderly patients most often in the head and neck regions.
- Amelanotic melanoma (<5%): can be missed and diagnosed at a later stage, as it can mimic benign skin conditions, and thus is referred to as a “great pretender”
- Acral lentiginous: 2–8% of all melanomas; however, most common melanoma in black or Asian patients; found in palmar, plantar, and subungual areas
- Subungual melanoma (0.7–3.5%): dark longitudinal stripe under the nail plate; Hutchinson nail sign is when brown or black pigment extends from the nail to the cuticle and proximal or lateral nail folds.
- Desmoplastic melanoma (~1%): “neurotropic melanoma” or “spindled melanoma” with an abundance of fibrous tissue; demonstrates sarcoma-like tendencies with increased hematogenous spread; presents as a slow-growing lesion that is scar-like (no history of injury at the site is noted); often seen in the head and neck
- System(s) affected: skin/exocrine
Lentigo maligna, slowly enlarging pigmented lesion, is most common in elderly patients. This type is usually found on the face, beginning as a circumscribed macular patch of mottled pigmentation showing shades of dark brown, tan, or black.
Large congenital nevi (>5 cm) are risk factors and have a >2% lifetime risk of malignant conversion. Blistering sunburns in childhood significantly increase risk.
No increased risk of melanoma in pregnancy. In the case of recent melanoma treatment, it is recommended to wait 1 to 2 years prior to becoming pregnant, as melanoma can spread to the placenta.
- In 2017, an estimated 87,110 Americans were diagnosed with melanoma, with approximately 9,730 expected deaths (2).
- Predominant age: median age: 62 and 54 years for men and women respectively; >50% of all individuals with melanoma are between 20 and 40 years of age.
- Predominant sex: male > female (1.5 times)
- Melanoma is more than 20 times more common in whites than in African Americans (2).
- Minority groups demonstrate increased rates of metastasis, advanced stages at diagnosis, thicker initial lesions, earlier age at diagnosis, and overall poorer outcomes.
- Low socioeconomic status associated with higher incidence of melanoma
Etiology and Pathophysiology
- DNA damage by UVA/UVB exposure
- Tumor progression: initially may be confined to epidermis with lateral growth, may then grow into dermis with vertical growth
- Dysplastic nevus syndrome is a risk factor for development of melanoma. Close surveillance is warranted.
- 8–12% of patients with melanoma have a family history of disease.
- Mutation in CDKN2A (p16) is found in 1/3 of patients with family incidence of melanoma.
- Mutations in BRAF (V600E) implicated in 50–60% of cutaneous melanomas
- Familial atypical mole malignant melanoma (FAMMM) syndrome characterized by >50 atypical moles, +FH of melanoma, clinical diagnosis (3)
- Genetic predisposition, persona/family history of melanoma
- UV-A and UV-B exposure
- History of >5 sunburns during lifetime
- History of intense intermittent sun exposure
- Previous pigmented lesions (especially dysplastic melanocytic nevi)
- Fair complexion, freckling, blue eyes, blond/red hair
- Highest predictor of risk is increased number of nevi (>100).
- Tanning bed use: 75% increased risk if first exposure before age 35 years
- Changing nevus (see ABCDE criteria)
- Large (>5 cm) congenital nevi
- Chronic immunosuppression (chronic lymphocytic leukemia, non-Hodgkin lymphoma, AIDS, or posttransplant)
- Blistering sunburns in childhood
- Living at high altitude (>700 meters or 2,300 feet above sea level)
- Occupational exposure to ionizing radiation
- Avoidance of sunburns, especially in childhood
- Use of sunscreen with at least SPF 30 to all skin exposed to sunlight, reapplying regularly and after toweling or swimming
- Avoid tanning beds; class 1 carcinogen by World Health Organization (WHO)
- Screening of high-risk individuals, especially males >50 years
- Education for proper diagnosis plays a large factor in prevention.
- Any suspicious lesions should be biopsied with a narrow excision encompassing the entire breadth plus sufficient depth of the lesion. Options include elliptical excisions, punch, or shave biopsies.
Commonly Associated Conditions
- Dysplastic nevus syndrome
- >50 nevi. These individuals have higher lifetime risk of melanoma than the general population, as 50% of all melanoma arise in preexisting nevi.
- Giant congenital nevus: 6% lifetime incidence of melanoma
- Xeroderma pigmentosum is a rare condition associated with an extremely high risk of skin cancers, including melanoma.
- Psoriasis after psoralen-UV-A (PUVA) therapy