Melanoma

Background

• Melanoma, a malignant tumor of melanocytes, is a characteristically aggressive cancer that most commonly affects the skin. Rarely, it may involve other sites such as mucosa, intestines, the brain, or the uvea.
• There are 4 types of cutaneous invasive melanoma:
  • Superficial spreading melanoma is the most common type, accounting for about 70% of cutaneous melanomas. It is typically seen on sun-exposed skin, particularly areas of intermittent exposure, such as the posterior legs in women, and on the back in men.
  • Nodular melanoma accounts for about 5% of all melanomas and appears more commonly in men, occurring at any site, and is often associated with ulceration.
  • Acral lentiginous melanoma accounts for about 5%-10% of all melanomas, but appears to be the most common type of melanoma in patients who are Asian and Hispanic, and patients of African descent.
  • Lentigo maligna (invasive melanoma) accounts for about 4%-15% of cutaneous cases and usually develops from lentigo maligna (in situ) on sun-damaged skin.
• Although melanoma can present at any age, about 50% of newly diagnosed cutaneous melanoma cases present in patients aged 35-65 years.
• Patients with fair skin or hair, increased exposure to sun or other forms of ultraviolet radiation, multiple nevi, immunosuppression, or a family history of melanoma appear to be at increased risk for melanoma, and should be counselled on preventive strategies, sun protection, and self-examination of skin.
• For cutaneous melanomas ≤ 1-mm deep, 10-year survival is over 80% depending on type and location, but more invasive and metastatic melanomas are associated with a poor 5-year prognosis.

Evaluation

• Assess symptoms and risk factors including personal and family history or skin cancer. Examine suspicious lesions by the ABCDE criteria or revised 7-point checklist, and in reference to other nevi on the patient.
• Suspicious lesions may appear as an "ugly duckling" lesion compared to other nevi on the patient. Suspicious lesions are typically characterized by the ABCDE, or revised 7-point checklist criteria.
  • ABCDE criteria includes:
    • A - asymmetry
    • B - border irregularities
    • C - color variation (mottled, shades of brown, black, gray, and white)
    • D - diameter > 6 mm (pencil eraser)
    • E - evolving size, shape, surface (raised, bleeding, crusting), shades of color, or symptoms (itchiness, tenderness)
  • The revised 7-point checklist for melanoma (also known as revised Glasgow checklist) describes change in size, irregular shape or color, diameter ≥ 7 mm, inflammation, oozing, and change in sensation of a suspicious lesion.
• The differential diagnosis of melanoma includes other nevi types, epithelial or mesenchymal neoplasms, and pigmented actinic keratoses and similar lesions.
• Dermoscopy may be used for a more detailed exam of suspicious lesions, but a biopsy, preferably an excisional biopsy, is required to confirm the diagnosis.
• For metastatic disease, tissue should be tested for BRAF mutations, which suggest susceptibility to BRAF-inhibitor drugs (Strong recommendation).

Management

• Treatment of melanoma is based on TNM staging of the tumor as determined by depth, ulceration, mitotic rate, and presence or absence of nodal or distant metastases.
• Local wide excision of the lesion is the primary treatment for cutaneous melanoma (Strong recommendation). Recommended excision margins are:
  • 5-mm margin for melanoma in situ
  • 1-cm margin for melanomas < 1-mm thick
  • 1- to 2-cm margin for melanomas ≤ 2-mm thick
  • 2-cm margin for melanomas > 2-mm thick
• Consider a sentinel lymph node biopsy (SLNB) for staging in patients with tumors that have pathologic features with higher risk of positivity, such as Breslow depth < 0.8 mm with ulceration or other high risk features and lesions > 0.8 mm thick (Weak recommendation).
• For advanced melanoma and/or patients at high risk of developing metastatic disease, consider adjuvant targeted therapy with nivolumab, pembrolizumab or targeted therapy with dabrafenib/trametinib, or adjuvant radiation therapy (Weak recommendation).
• For patients with metastatic or unresectable melanoma and good clinical status, consider systemic treatment. Options include:
  • Immunotherapy with a checkpoint inhibitor, such as nivolumab, pembrolizumab, or nivolumab plus ipilimumab (Strong recommendation).
  • Or, for patients with positive BRAF mutations, use targeted therapy, preferably with combination treatment of dabrafenib plus trametinib, vemurafenib plus cobimetinib, or encorafenib plus binimetinib (Strong recommendation).
  • An alternative option is combination targeted therapy and anti-PD-L1 therapy if BRAF V600 present, such as atezolizumab plus vemurafenib and cobimetinib (Weak recommendation).
• There is limited evidence to guide surveillance, but consider a follow-up every 3-12 months with clinical skin exam and lymph node palpation, depending on the risk of recurrence or risk for a second primary tumor (Weak recommendation).