Malignant melanoma is a relatively common neoplasm that not long ago was considered almost uniformly deadly. Although the great preponderance of melanomas arise in the skin other sites origin include the oral and anogenital mucosal surfaces, esophagus , meninges, and notably the eye. The following comments apply to cutaneous melanomas. Intaocular melanomas.

Today as a result of increased public awareness of the earliest signs of skin melanomas most are cured surgically. Nonetheless the incidence of these lesions is on the rise, necessitating vigorous surveillance for their development.

As with epithelial malignant neoplasms of the skin sunlight appears to play an important role in the development of skin malignant melanoma. For example men commonly develop this tumor on the upper back whereas women have a relatively high incidence on both the back and the legs. Lightly pigmented individuals are at higher risk for the development of melanoma than are darkly pigmented individuals. Sunlight, however, does not seem to be the only predisposing factor, and the presence of apreexisting nevus, hereditary factors or even exposure to certain carcinogens may play a role in lesion development and evolution.

Molecular Geletics

The molecular basis for nonheritable forms of melanoma is incompletely understood and much of out current knowledge is based upon evaluation of the approximately 10% of melanomas that tend to run in families. As stated before these melanomas are often ( but not invariably) associated with multiple sysplastic nevi. Some of the suspected melanoma associated genes in this setting include: (1) the CMM1 gene on chromosome lp36; (2) the tumor suppressor gene p16 mapped to chromosome 9p21 (Genetic analyses have revealed germline mutations in this gene in certain melanoma patients and their family members. It may be recalled that this tumor suppressor gene is an inhibitor of cyclin dependent kinase4 [CDK 4] and such negatively regulateds the cell cycle and (3) the cyclin dependent kinase gene CDK4on chromosome 12q14. Transgenic mice with melanocyte specific expression of activated ras on a genetic background dificient for alleles of p16 exhibit accelerated development of melanoma thus confirming the role of this tumor suppressor in the pathogenesis of melanomas.

Clinical Features

Malignant melanoma of the skin is usually asymptomatic although itching may be an early manifestation. The most important clinical sign of the disease is change in color in a pigmented lesion. Unlike benign (nondysplastic) navi, melanomas exhibit striking variations in pigmentation, appearing in shades of black , brown , red, dark blue, and gray. On occation , zones of white or flesh colored hypopigmentation are also present. The borders of melanomas are not smooth, round and uniform as in nevocellular nevi, but iregular and often notched. In summary the clinical warming signs of melanoma are (1)enlargement of preexisting mole, (2) itching or pain in apreexisting mole (3) development of a new pigmented lesion during elder life( irregularity of borders of apigmented lesion, and (5) variegation of color within a picmented lesion.