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; wait 1 to 2 years after treatment for pregnancy as melanoma can spread to the placenta.

Epidemiology

Incidence

• In 2023, the estimated number of newly diagnosed melanoma cases in Americans are 97,610, with an estimate of 7,990 deaths.
• Predominant age: Median age at diagnosis is 66 years.
• Predominant sex: male > female (1.5 times)
• Melanoma is >20 times more common in whites than in African Americans.
• Minority groups demonstrate increased rates of metastasis, advanced stages at diagnosis, thicker initial lesions, earlier age at diagnosis, and overall poorer outcomes.

Prevalence

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

Etiology and Pathophysiology

• DNA damage by UVA/UVB exposure
• Tumor progression: initially confined to epidermis with lateral growth, 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 (1)

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).
• 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
• Use of sunscreen with at least SPF 30 to all exposed skin; reapply regularly and after swimming.
• Avoid tanning beds; class 1 carcinogen by World Health Organization (WHO)
• 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
• Psoriasis after psoralen-UV-A (PUVA) therapy