Chapter 083. Cancer of the Skin (Part 1) Harrison's Internal Medicine > Chapter 83. Cancer of the Skin Melanoma Pigmented lesions are among the most common findings on skin examination. The challenge is to distinguish cutaneous melanomas, which may be lethal, from the remainder, which with rare exceptions are benign. Examples of malignant and benign pigmented lesions are shown in Fig. 83-1. Figure 83-1 Atypical and malignant pigmented lesions. The most common melanoma is superficial spreading melanoma (not pictured). A. Acral lentiginous melanoma is the most common melanoma in blacks, Asians, and Hispanics and occurs as an enlarging hyperpigmented macule or plaqu e on the palms and soles. Lateral pigment diffusion is present. B. Nodular melanoma most commonly manifests itself as a rapidly growing, often ulcerated or crusted black nodule. C. Lentigo maligna melanoma occurs on sun-exposed skin as a large, hyperpigmen ted macule or plaque with irregular borders and variable pigmentation. D. Dysplastic nevi are irregularly pigmented and shaped nevomelanocytic lesions which may be associated with familial melanoma. Epidemiology Melanomas originate from neural crest-derived melanocytes; pigment cells present normally in the epidermis and sometimes in the dermis. This tumor affects around 62,000 individuals per year in the United States, resulting in 7910 deaths. Melanoma is the fifth most common cancer in men (5% of cancers) and the sixth most common in women (4% of cancers). The tumor can affect adults of all ages, even young individuals (starting in the mid-teens); has distinct clinical features that make it detectable at a time when cure by surgical excision is possible; and is located on the skin surface, where it is visible. The incidence has increased dramatically (6% per year from 1973 to 1980, then 3% per year). Current lifetime risk ratio is 1:53 in males and 1:78 in females. The reason for this increase is uncertain but may involve increased recreational sun exposure, especially early in life. Individuals of similar ethnic background who immigrate after childhood to areas of high sun exposure (e.g., Israel and Australia) have lower melanoma rates than individuals of similar age who were either born in those countries or immigrated before age 10. The individuals most susceptible to development of melanoma are those with fair complexions, red or blond hair, blue eyes, and freckles and who tan poorly and sunburn easily. Other factors associated with increased risk include a family history of melanoma (~1 in 10 melanoma patients have a family member with melanoma), the presence of a clinically atypical mole (dysplastic nevus) or a giant congenital melanocytic nevus, the presence of a higher than average number of ordinary melanocytic nevi, and immunosuppression (Table 83-1). Individuals with 50 or more moles ≥2 mm in size have a 64-fold increased risk. About 30% of melanomas arise in a nevus. Some individuals with multiple primary melanomas and/or a strong family history have heritable mutations in the CDKN2A gene. Melanoma is relatively rare in heavily pigmented peoples. Dark-skinned populations (such as those of India and Puerto Rico), blacks, and East Asians have rates 10–20 times lower than lighter- skinned whites. In keeping with the role of sun exposure, the incidence is inversely correlated with the latitude of residence; at any latitude, darker-skinned persons have the lowest incidence. Melanoma is rare in children under age 10. Table 83-1 Risk Factors for Cutaneous Melanoma High risk (>50-fold increase in risk) Persistently changing mole Clinically atypical moles in patient with two family members with melanoma Adulthood (vs. childhood) >50 nevi ≥2 mm in diameter Intermediate risk (~10-fold increase in risk) Family history of melanoma Sporadic clinically atypical moles Congenital nevi (?) White ethnicity (vs. black or East Asian ethnicity) Personal history of prior melanoma Low risk (2- to 4-fold increase in risk) Immunosuppression Sun sensitivity or excess exposure to sun Source: Adapted from AR Rhodes et al: JAMA 258:3146, 1987. . Chapter 083. Cancer of the Skin (Part 1) Harrison's Internal Medicine > Chapter 83. Cancer of the Skin Melanoma Pigmented lesions are among the most common findings on skin. common cancer in men (5% of cancers) and the sixth most common in women (4% of cancers). The tumor can affect adults of all ages, even young individuals (starting in the mid-teens); has distinct. lighter- skinned whites. In keeping with the role of sun exposure, the incidence is inversely correlated with the latitude of residence; at any latitude, darker-skinned persons have the lowest