Melanoma

Melanoma, a highly malignant tumor arising from melanocytes, is the most common life-threatening dermatological disease. Risk factors include UV radiation exposure, particularly in light-skinned individuals that are easily sunburned, increasing age, family history, and immunosuppression. The superficial spreading melanoma is the most common subtype. Other subtypes, such as nodular melanoma, have a significantly worse prognosis because they tend to metastasize more rapidly. Invasive melanoma is particular in its propensity to metastasize to unusual locations that are not commonly affected by other malignancies. Immediate full-thickness surgical biopsy of the primary tumor is usually the best initial diagnostic test and may be therapeutic for localized disease. Chemotherapy, biologics, and/or radiation therapy are recommended for recurrent or widespread disease. Tumor thickness is the most important prognostic factor.

Most common life-threatening dermatological disease

References:^[1]

Epidemiological data refers to the US, unless otherwise specified.

• Origin
  • Melanocytes from the epidermal skin layer
  • A precursor lesion (e.g., congenital or atypical nevi, lentigo maligna) in ⅓ of cases
• Risk factors
  • UV radiation exposure
  • Light skin
  • Dysplastic nevi , giant congenital nevi, or inherited skin conditions (e.g., dysplastic nevus syndrome, familial atypical mole, melanoma syndrome, xeroderma pigmentosa)
  • Immunosuppression
  • Genetics ^[2]
    • BRAF gene mutations; V600E is the most common mutation ^[3]
    • CDKN2A gene mutations ^[4]

Appearance

• Pruritic, persistently bleeding skin lesion
• Dermoscopy should be used to examine lesions for ABCDE criteria:
  • A = Asymmetry
  • B = Border (irregular border with indistinct margins)
  • C = Color (new changes in pigmentation or variations in pigmentation within the same lesion)
  • D = Diameter > 6 mm
  • E = Evolving (new lesion or a lesion that changes in size, shape, or color over time)

Types of melanoma

Genitourinary melanoma (GU melanoma)

Overview ^[6]

• Rare (< 5%)
• Approx. 45% of all mucosal melanomas
• Most commonly affects female individuals (approx. 90%)
• Cause remains unknown.
• Expression of cell biomarkers such as PD-1 and PD-L1 in vulvar melanoma is significantly higher than in cutaneous melanomas.
• Prognosis is generally poor.

Types of GU melanoma ^[6]

Other

• Amelanotic melanoma
  • Nodules ranging from skin-colored to bright pink or red.
  • Diagnosis requires histological confirmation.
• Uveal melanoma
• Subungual melanoma
  • Rare subtype of acral lentiginous melanoma that develops within the nail unit
  • Commonly manifests as melanonychia (i.e., brown to black longitudinal band) > 3 mm involving a single nail
  • Features suggestive of malignancy
    • Rapid enlargement
    • Irregular or blurred borders
    • Variegated pigmentation
    • Triangular shape
    • Nail dystrophy, fissuring, or splitting
    • Hutchinson sign of the nail

• A full-thickness excisional biopsy (best diagnostic test) with 1–3 mm margins is indicated in all suspicious lesions. ; ^[9]
  • An excisional biopsy procedure used to obtain a tissue sample of skin that includes every layer (i.e., healthy and abnormal tissue)
  • A second resection may be necessary if the melanoma is histologically confirmed.
  • Pathology shows s100-protein positive, epithelioid cells with fine granules in cytoplasm
• Staging tests (e.g., ultrasound or MRI) once diagnosis confirmed: to determine tumor thickness, spread to lymph nodes, or distant metastasis ^[10]

Complete excisional biopsies are always preferred over incisional biopsies, as they allow tumor thickness to be properly estimated!

Benign lesions commonly resemble melanomas and should be biopsied to rule out cancer (see “Benign skin lesions”).

The differential diagnoses listed here are not exhaustive.

• Surgical excision: full-thickness excision with appropriate safety margins
  • 0.5–1 cm safety margin: melanoma in situ (T0)
  • Other margins according to Breslow depth: thickness from the granular layer to the lowest detectable tumor cell. The Breslow index correlates with the risk of metastasis.

• Medical therapy
  • BRAF kinase inhibitor (e.g., vemurafenib) is used in metastatic or unresectable melanomas that have the BRAF V600E mutation (substitution of glutamic acid in place of valine at amino acid position 600 caused by activating mutations in the BRAF gene) ^[11]
  • Immunotherapy: checkpoint inhibitors (e.g., pembrolizumab, nivolumab) for tumors positive for PD-1 mutations ^[12]

The gold standard is immediate, complete excision of the tumor.

Metastatic disease ^[13]

• Metastatic melanoma may spread to lymph nodes, liver, lung, brain, and bone
• May also metastasize to locations not typically affected by metastatic malignancies ^[14]
• Up to 5% of metastatic cases have no known primary tumor.
• Characteristic black pigmentation

We list the most important complications. The selection is not exhaustive.

• Negative prognostic factors
  • Epidemiological features: male sex
  • Clinical features: type , localization , and presence of ulcerations
  • Melanoma has a significant risk of metastasis, which is associated with a poorer prognosis.
  • Tumor thickness, as determined from the Breslow thickness, is the most important prognostic factor.
  • Regression

• One-Minute Telegram 74-2023-1/3: Unclear benefit of skin cancer screening