Causes of Melanoma

Melanoma skin cancer ---> Causes of melanoma

Numerous environmental and genetic risk factors have been implicated in the development of cutaneous melanoma. Risk factors include ultraviolet light (UVL) exposure, fair complexion/inability to tan, blue or green eyes, blonde or red hair, freckling, history of actinic keratosis or nonmelanoma skin cancer, history of blistering or peeling sunburns, immunosuppression, personal or family history of melanoma, xeroderma pigmentosa, atypical (dysplastic) nevus, more than 100 normal nevi, and giant congenital melanocytic nevus. Patients with a significant history of sun exposure are at particularly high risk, especially if they experienced peeling or blistering sunburns, even during childhood. Melanoma occurs infrequently in skin of color, suggesting that skin pigment plays a protective role. Melanoma incidence is subject to large geographic and ethnic variations, mainly because of an inverse correlation with latitude and with degree of skin pigmentation. Populations residing closer to the equator have a higher incidence of melanoma. Certainly UVL exposure from sun or artificial light sources is considered the best-known risk factor. However, UVL exposure does not cause all or even most melanomas.
Adults with more than 100 clinically normal-appearing nevi, children with more than 50 clinically normal-appearing nevi, and any patient with atypical or dysplastic nevi are at risk. A prior history of melanoma places a patient at increased risk, with 5% to 10% of individuals developing a second primary melanoma. This risk of developing a second primary is lifelong and can occur anywhere on the skin. Therefore, long-term surveillance with a thorough total body examination is recommended.
A genetic component has been implicated in the pathogenesis of melanoma. Of patients with melanoma, 10% to 15% report a positive family history. The genetic etiology of melanoma represents an area of future discovery.
The hereditary nature of cutaneous melanoma was also noted in the 1970s. Members afflicted with the B-K mole syndrome, named after two families, acquired large, irregular, and dysplastic nevi, often in sun-protected regions of the body such as the scalp and trunk. Familial association of melanoma among individuals with atypical nevi, is termed Familial Atypical Multiple Mole-Melanoma Syndrome, or FAMMM syndrome, with an autosomal dominant inheritance pattern. An atypical nevus is not a pre melanoma but represents a genetic marker for increased risk of development of melanoma, which may occur anywhere on the skin surface including sun-protected sites. In fact more than 50% to 75% of melanomas develop on clinically normal skin de novo, not in preexisting melanocytic lesions.
Xeroderma pigmentosa (XP) is a rare autosomal recessive disorder associated with a reduced or absent ability to repair DNA damaged by ultraviolet light. Consequently, this disorder results in the development of multiple primary cutaneous malignancies, including melanoma as well as BCC and SCC. Individuals are usually diagnosed with their first cancer before the age of 10 years. Unfortunately, the development of skin cancers is relentless.
Congenital melanocytic nevi (CMN) are present at birth or appear within the first 6 months of infancy. An estimated 1% to 6% of children are born with CMN. The nevi are classified by size. Small CMN measure less than 1.5 cm in diameter and account for the majority of lesions. Medium CMN measure between 1.5 and 19.9 cm in diameter. Large CMN, also termed giant congenital nevi, measure 20 cm or greater. This large size can lead to significant cosmetic and psychosocial implications. The risk of melanoma development in small and medium-size CMN is similar to any other area of skin. Melanoma development in small and medium CMN usually occurs after childhood and arises from the dermoepidermal junction, making early detection feasible. Routine prophylactic removal of small and medium CMN is rarely indicated in the absence of signs or symptoms for malignant progression. Conversely, giant congenital nevi carry an increased risk for melanoma, with an estimated rate of 5% to 20%. Of giant congenital nevi that progress to melanoma, 70% are diagnosed prior to age 10 years. Melanoma can originate deep in the epidermis in giant congenital nevi. Consequently, diagnosis within the setting of giant congenital nevi is challenging and may develop deep in the skin with a more advanced primary lesion.