Melanoma
Melanoma can be found in the skin, however, also in the oral and anogenital areas of mucosa, the esophagus, the meninges, and also commonly the eye. Due to increased awareness through puclic programs, melanomas have been found early and easily treated before they spread. These lesions have been shown epidemiologically to be increasing for unknown reasons, but likely to increases in sunlight exposure, and more stronger radiation from loss of ozone. Upper abck melanoma is seen in men more frequently, in comtrast to women who have melanoma commonly also on their legs. In addition, to sunlight, pre-existing moles, termed dysplastic nevi, familial factors (family history of cancer) and exposure to certain chemicals that can cause cancer are well-known to be implicated in melanoma formation.
Melanoma of the skin is usually asymptomatic. This is why patients usually present late. The main clinical feature of melanoma, is variations in pigment, which different shades of black, brown, blue, gray and even white (areas where inflammatory cells have cleared malignant melanoma cells). Melanomas are usually more than a centimeter in diameter, have irregular borders, enlarge over time, and can be associated with pain and bleeding.
Melanoma cells are larger than normal melanocytes, contain large irregular nuclei with eosinophilic nucleoli (high in protein) and chromatin clumpings at the nucleus periphery.
It is crucial to understand the growth patterns of melanoma. These are the radial and vertical growth phases. Melanoma usually initially grows horizontally along the epidermal-dermal junction or just below it. It is during this stage, that melanoma is not metastazing. Variants of melanoma that only have radial growth are lentigo maligna, superficial spreading melanoma and acral lentiginous. It is worrisome if the melanoma begins to grow vertically. This occurs with time, so it is therefore crucial to excise the melanoma during the radial growth phase. During the vertical phase, the melanoma cells begin to lack cellular maturation, become smaller and more immature in appearance, and form nests of cells. Metastasis is then of main concern. The probability of metastasis can be easily determined by just measuring the depth of verrtical growth below the basal epidermal layer. Cells here begin to form nodules. Nests of melanoma cells can also be found in the epidermis.
Familial melanoma accounts for 10 to 15% of all melanomas. This is commonly seen with dysplastic nevi transforming into melanoma cells. Familial cancer syndromes with melanoma include, dysplastic nevus syndrome, familial atypical multiple mole-melanoma syndrome, also known as familial melanoma syndrome (FMS). Using information from these familial syndromes, the molecular pathogenesis of melanoma was elucidated.
The main genetic locus implicated in melanoma is on chromosome 9p21, which harbors p16INK4. p16INK4 is a cyclin-dependent kinase inhibitor 2, also known as CDNK2. It has been found to be frequently deleted within melanoma cells. Loss of this protein leads to cell cycle control loss, throuogh phosphorylation or the retinoblastoma tumor suppressor, RB, release of E2F from RB, and subsequent cycling of the cell without any inhibition. However, this locus is mutated in only 10% of sporadic melanoma cases.