الفهرس 
Epidemiology and Etiology of Malignant MelanomaOnly 14 pages are availabe for public view
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Abstract
Malignant Melanoma is a neoplastic disorder produced by malignant transformation of the normal cutaneous melanocytes, and less frequently of retinal pigment epithelial cells (uveal melanoma).
Malignant melanoma is the sixth-most-common United States cancer diagnosis. The actual incidence of melanoma is increasing more rapidly than that of any other malignancy, with 59,940 cases of invasive melanoma and 8,110 melanoma deaths in the United States in 2007.
The incidence of cutaneous melanoma in Egypt is low, contributing about 0.65 % of all cancers.
One hundred and sixty thousand new cases of cutaneous melanoma are diagnosed world wide each year. It is particularly common in the white populations living in sunny climates. According to the WHO report, about 48,000 deaths are registered annually world wide due to malignant melanoma.
Generally an individual risk for developing melanoma depends on two factors: intrinsic and environmental factors; Intrinsic factors are generally individual’s family history and inherited genotypes, while the most relevant environmental factor is sun exposure.
Possible significant elements in determining risk include the intensity and duration of sun exposure, the age at which sun exposure occurs and the degree of skin pigmentation. Exposure during childhood is a more important risk factor than exposure in adulthood. Occasional extreme sun exposure resulting in sunburn is causally related to melanoma while those with more chronic long term exposure (out door workers) may develop protective mechanisms. Melanoma is most common on the back in men and the extremities in women (area of intermittent sun exposure).
Epidemiologic studies suggest that exposure to the ultraviolet radiation (UVA and UVB) is one of the major contributors to the development of melanoma. UV radiation causes damage to the DNA of the cell. When the cell divides these mutations are propagated to new generations of cells.
The transition from melanocyte to metastatic melanoma involves several histologic intermediates, including melanocytic atypia, atypical melanocytic hyperplasia, radial growth phase melanoma, vertical growth phase melanoma, and metastatic melanoma.
Identification of features that may mark lesions suspicious for melanoma can be simply recalled using the mnemonic ABCDE. A stands for asymmetry, B for borders that are irregular or diffuse, C for color variegation, D for diameter more than 5 mm, and E signifies enlargement of the lesion. Bleeding and ulceration occurs in 10% of localized melanomas and 54% of late melanomas and is a poor prognostic finding.
Early detection of melanoma is the most important prognostic criterion, as early melanomas can be cured.Biopsy of suspected melanoma is important, as histological measurement of the depth of the tumor is the most important prognostic criterion and will be used to determine appropriate surgical management,the techniques used are excisional biopsies, incisional biopsies, punch biopsies, and deep shave biopsies and is complemented with elective lymph node dissection and most recently with Sentinel node mapping which is used to determine which patients had micrometastases to the draining lymph node.
Features that affect prognosis are patient age and gender, tumor thickness in millimeters (Breslow’s depth), depth related to skin structures (Clark level), presence of ulceration, stage of melanoma, type of melanoma, location of lesion, presence of lymphovascular invasion, presence of tumor infiltrating lymphocytes (if present, prognosis is better), presence of satellite & In-transit metastases and presence of regional or distant metastasis.
When melanoma has spread to lymph nodes the most important factor is the number of lymph nodes with malignancy rather than their dimensions and the Extent of malignancy within a node is also important, as micrometastases in which malignancy is only microscopic, have a more favorable prognosis than macrometastases.
The most useful prognostic factors in clinical practice for localized melanoma are Breslow thickness, presence of lymph node involvement, and ulceration. Clark level has not proven useful except perhaps in thin (1 mm) melanoma. In metastatic disease, location of metastatic site and lactate dehydrogenase elevation.
Also from the factors which affect the prognosis of melanoma is the adjuvant therapy which includes the usage of interferon, systemic chemotherapy, immunotherapy, biochemotherapy and perfusion chemotherapy. The use of high dose of interferon alpha-2b improves the survival of patients with melanoma > 4mm thick; adjuvant treatment with low dose interferon alpha-2b diminishes the occurrence of metasteses and prolongs the disease free survival in patients with melanoma > 1.5 mm.
Systemic chemotherapy is used in patients with advanced stage 3 (unresecetable regional metasteses) or stage 4 (distant metasteses) melanoma. The chemotherapeutic agents used are Dacarbazine, Temozolomide (the active metabolite of Dacarbazine) or combination chemotherapy.
Immunotherapy is directed towards modulating or inducing the immune system against melanoma, the usage of interleukin-2 (IL-2) as a single agent has been utilized in metastatic melanoma. Isolated limb perfusion is used for melanoma of the extremities; it is considered the most effective method of treatment for local recurrent or intransit metastases of an extremity.
Radiation therapy is often used after surgical resection for patients with locally or regionally advanced melanoma or for patients judged to be medically inoperable or refuses surgery or with unresectable distant metastases.
The improved understanding of the oncogenic events in melanoma provides novel targets for therapeutic intervention. Novel targeted therapies are being developed that block the oncogenic signaling from mutations or genetic amplifications of members of the MAPK and PI3K signal transduction pathways (Sorafenib & mTOR inhibitor temsirolimus)
Melanoma patients must follow a follow up schedule of visit every 3 months for 2 years, followed by every 6 months for 3 years, then yearly for at least 5 years.