Melanoma

Overview
  • Melanoma is a malignant neoplasm of pigment-forming cells: Melanocytes and nevocytes. The incidence of melanoma is increasing and typically occurs in early and middle-aged adults, in the second through fifth decades. The metastatic potential of melanoma is directly related to its depth of dermal invasion and thus early identification and excision is critical.
Pathogenesis
  • The precise pathogenesis of melanoma is unclear. Risk factors include fair skin, a history of frequent sunburns, and large numbers of nevi. Rare familial syndromes have been described. In recent years, whole-genome sequencing of these tumors have revealed frequent activating mutations in certain tyrosine kinase genes.
Gross Morphology
  • Overview
    • The ABCDE criteria have been popularized for clinical detection of melanoma. Accordingly, melanomas tend to display an Asymmetric shape, have an irregular Border, show variegated and non-uniform Color, a Diameter greater than 6mm, and Evolve over time. Additional clues that should raise suspicion include a newly pruritic, bleeding, or ulcerated pigmented lesion.
    • Several variants of melanoma have been described based on their growth patterns and are discussed below. In some variants neoplastic cells tend to grow radially and superficially before invading more deeply, thus carrying a better prognosis, while in others there is little to no radial growth phase preceding deep invasion.
  • Lentigo Maligna Melanoma
    • This variant displays the longest radial growth phase, expanding up to 7cm, prior to deeper invasion. It is often preceded by "Lentigo Melanoma", also known as "Melanoma in situ" in which neoplastic cells spread superficially only within the basal layer of the skin. This variant typically occurs on the head and neck.
  • Superficial Spreading Melanoma
    • This variant also displays a long radial growth phase, expanding up to 3cm, prior to deeper invasion. It is typically found on the trunk in either gender as well as the lower legs in women.
  • Nodular Melanoma
    • Nodular melanomas display almost no radial growth phase and immediately dive into the dermis. These tend to display the poorest prognosis and are infrequently found prior to metastasis
  • Acral Lentiginous Melanoma
    • This variant occurs on the acral surfaces, including the palms and soles, and is more common in Blacks.
Histological Morphology
  • Histological diagnosis of melanoma is extremely challenging and a large number of clues can argue for or against a pigmented lesion representing a melanoma. Beyond diagnosis, pathology is critical for prognosis as the five-year survival rate of the patient is highly dependent on the "Breslow Depth" of the lesion: The number of millimeters below the surface of the skin that neoplastic cells are found. The Breslow depth also dictates the size of the margin used to excise the lesion.
Clinical Consequences
  • If treated at an early stage when tumor cells have not invaded significantly, melanoma can be curable; however, as the depth of invasion increases so does the probability of metastasis. Remarkably, patients successfully treated for melanoma have been shown to harbor metastasis even decades later.