Description

• 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 invasive cutaneous melanomas include the following:
  • Superficial-spreading melanoma: approximately 70% of cases; occurs in sun-exposed areas (trunk, back, and extremities); most <1 mm thick at diagnosis; when seen in younger patients, presents as a flat, slow growing, irregularly bordered lesion
  • Nodular: 15–30% of cases; present in older patients; tendency to ulcerate and hemorrhage; most commonly thick and pigmented; most common melanoma >2 mm
  • 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 10–15% of cases; it is most commonly seen in elderly patients most often in the head and neck regions.
  • Acral lentiginous: <5% of all melanomas; however, most common melanoma in black or Asian patients; found in palmar, plantar, and subungual areas; can mimic other skin abnormalities, including warts, calluses, tinea pedis, or ingrown toenails
    • An important subtype of acral lentiginous melanoma is subungual melanoma. From the nail matrix, presents as dark stripe under the nail plate; Hutchinson nail sign when brown or black pigment extends from the nail to the cuticle and proximal or lateral nail folds
  • Amelanotic melanoma: <5% of cases; can be missed and diagnosed at a later stage because it can mimic benign skin conditions, and thus is referred to as a “great pretender”
  • Desmoplastic melanoma: ~1% of cases; “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

Geriatric Considerations
Lentigo maligna 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.

Pediatric Considerations
Large congenital nevi (>5 cm) are risk factors and have a >2% lifetime risk of malignant conversion. Blistering sunburns in childhood significantly increase risk.

Pregnancy Considerations
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 because melanoma can spread to the placenta.

Epidemiology

Incidence

• In 2020, 100,350 Americans are estimated to be newly diagnosed with melanoma, with approximately 6,850 expected deaths (1).
• Predominant age: median age at diagnosis 65 years (https://www.cancer.gov/)
• Predominant sex: male > female (1.5 times)
• Melanoma is >20 times more common in whites than in African Americans (1).
• 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

Prevalence

• Melanoma is the fifth most common type of cancer in the United States
• Lifetime risk: men: 1/28; female: 1/4 1 (1)
• 1.2% of all cancer deaths (1)

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

Genetics

• 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.
• 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 (2)

Risk Factors

• Genetic predisposition, personal/family history of melanoma
• UVA and UVB exposure
• History of >5 sunburns during lifetime, blistering sunburns in childhood
• Previous pigmented lesions (especially dysplastic melanocytic nevi)
• Fair complexion, freckling, blue eyes, blond/red hair
• Highest predictor of risk is increased number of nevi (>50).
• 70% of melanomas are de novo, not existing from previous nevi (2)
• 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)
• Living at high altitude (>700 meters or 2,300 feet above sea level)
• Occupational exposure to ionizing radiation

General Prevention

• Avoidance of sunburns, especially in childhood. Seek shade and avoid midday sun.
• Use of broad-spectrum 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 with 1- to 3-mm margins that encompass the entire breadth plus sufficient depth of the lesion. Options include elliptical excisions, punch, or deep shave biopsies.

Commonly Associated Conditions

• Dysplastic nevus syndrome
• >50 nevi. These individuals have higher lifetime risk of melanoma than the general population because 30% 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