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Definition: A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines. Pathophysiology: The sequence of events where normal melanocytes transform to melanoma cells which is known as melanoma genesis is poorly understood. It involves a process of progressive genetic mutations that a) alter cell proliferation, differentiation and death and b) impact susceptibility to the carcinogenic effects of ultraviolet radiation. Prevention: Examine your skin regularly, especially those with red hair or blue eyes. Protect your skin: Stay out of the sun during the midday hours (10 am to 4 pm). Wear protective clothing such as a wide brim hat, shirts with sleeves to cover shoulders and tight woven clothing to keep sunlight out. Use sunscreen everyday with an SPF of at least 15. Use a higher SPF when you are at higher elevations. Avoid sunbathing and tanning salons. Risk Factors: o Presence of xeroderma pigmentosum or familial atypical mole melanoma syndrome. o Abundance of atypical/dysplastic nevi in familial melanoma. o Melanoma in first-degree relative(s). o Previous diagnosis of melanoma. o Male sex. o Age older than 50 years. o History of excessive sun exposure or sunburns. o Large congenital nevi (>20 cm diameter in adult). o Immunosuppression. o Fair skin types (blue/green eyes, blond or red hair, light complexion, sun sensitivity). Signs and Symptoms: The most common warning sign for melanoma is a changing mole or blemish. Other warning signs are a variation in color and/or an increase in diameter, height, or asymmetry of borders of a pigmented lesion. Symptoms such as bleeding, itching, ulceration and pain in pigmented lesion are less common but require evaluation. ABCDE: Asymmetry: The lesion is not symmetrical on both sides. Border irregularity: The edges are ragged, notched or blurred. Color variation: Lesion consists of multiple colors which may be shades of tan, brown, black, white, reddish, or blue. Diameter: A diameter greater than 6 mm, although some melanomas may be smaller. Evolution: This is the most crucial characteristic. Watching for changes in the lesion over time is critical.

Diagnostic Tests: Complete Chemistry Panel: Elevated levels of alkaline phosphatase, total protein and albumin may signal a metastatic disease. Biopsy of Suggested Lesion: A complete biopsy of the suggested lesion is preferred and should include 1-2 mm margin of healthy skin. All layers should be included in the biopsy therefore shave biopsies are contraindicated. Treatment: Surgery: Definitive treatment for early stage melanoma. A wide local excision with sentinel lymph node biopsy and/or elective lymph node dissection (LND) is considered the mainstay of treatment for patients with primary melanoma. In patients with solitary or acutely symptomatic brain metastases, surgical management may alleviate symptoms and provide local control of disease. Adjuvant Therapy: Gould Rothberg et al developed a prognosis marker where adjuvant therapies are favorable. A favorable prognosis was predicted by the following criteria:  ATF2 ln(non-nuclear/nuclear AQUA score ratio) greater than -0.052  p21(WAF1) nuclear compartment AQUA score greater than 12.98  p16(INK4A) ln(non-nuclear/nuclear AQUA score ratio) -0.083 or less  Beta-catenin total AQUA score greater than 38.68  Fibronectin total AQUA score 57.93 or less Primary tumors that met 4 to 5 criteria were considered low risk. Lose that met 3 or less criteria were at high risk. Chemotherapy: No standard systemic therapeutic regimens that offer prolongation of survival in patients with metastatic melanoma. Ipilimumab: Anti–cytotoxic T-lymphocyte associated protein 4 (CTLA-4) is a humanized antibody directed at a downregulatory receptor on activated T-cells. The proposed mechanism of action is inhibition of T-cell inactivation, allowing expansion of naturally developed melanoma-specific cytotoxic T-cells. Ipilimumab was approved by the FDA in 2011 for unresectable or metastatic cancer. Peginterferon Alfa-2b: Peginterferon alfa-2b is an immunomodulatory cytokine that enhances phagocyte and lymphocyte activity. It was approved by the FDA in March 2011 as adjuvant therapy following definitive surgical resection, including complete lymphadenectomy.
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