Melanocytes are melanin-producing cells that originate in the neural crest and migrate in utero to the skin, mucous membranes, eyes, inner ear, and central nervous system (CNS). Tumors of melanocytes in the skin are composed of one of three types of cells: nevus cells, epidermal melanocytes, and dermal melanocytes (Box 68.1). All melanocytic tumors, except freckles, may be present at birth. Freckles are acquired later in childhood. Melanocytic nevi are further classified as junctional, intradermal, or compound when the location of nevus cells is within the epidermis, the dermis, or both, respectively.

Congenital melanocytic nevi (CMN) occur in 1% to 6% of all newborns and are classified according to the size they attain or are predicted to attain in adulthood. Nevi that are less than 1.5 cm in diameter are classified as small, nevi between 1.5 and 19.9 cm in diameter are classified as medium, and nevi that are 20 cm or greater in diameter are classified as large. The very large CMN involving a major portion of the body are often referred to as “giant” or “bathing trunk” nevi. CMN typically present as sharply demarcated, often multicolored and hairy, dark brown patches. In some CMN, especially the larger ones, the overlying skin can be thickened and verrucous, and satellite lesions may be present. CMN are significant because of their increased risk for development of malignant melanoma. The risk for developing melanoma increases with the size of the nevus. The lifetime risk for developing melanoma in patients with CMN less than 20 cm in diameter is estimated to be between 0% and 4.9% with most melanomas developing at or after puberty, whereas the lifetime risk of developing melanoma in patients with CMN greater than 20 cm is estimated to be between 4.5% and 10% with most melanomas arising before puberty. If prophylactic removal is decided, it should be performed early in life for large CMN and any time up to puberty for small and medium CMN. Features that suggest development of melanoma in a CMN include change in color, irregular or scalloped border, change in size or thickness, variation in color within the lesion, bleeding, or ulceration. CMN may have irregular borders and variation in color and thickness from the outset, making it difficult to follow these lesions for early malignant changes (Fig. 68.1). All CMN with atypical or suspicious features should be excised regardless of size.

Patients with large CMN are also at risk for neurocutaneous melanocytosis. The highest risk for melanoma or neurocutaneous melanocytosis is seen in patients with large CMN in a posterior axial location, especially when associated with satellite smaller CMN. Neurocutaneous melanosis can result in seizures, hydrocephalus, or focal neurologic defects. A risk exists of developing a primary malignant melanoma in the leptomeningeal lesions as well as the cutaneous CMN.

Often referred to as Mongolian spots, dermal melanocytosis (DM) is characterized by blue-gray, poorly defined patches
that are most commonly seen overlying the sacral region of the newborn. It is the most commonly encountered congenital pigmented lesion; however, there are marked racial differences in prevalence. It is seen in 95% of black, 81% of Asian, 46% to 70% of Hispanic, and 10% of white infants. The lesions are due to the delayed disappearance of dermal melanocytes. To help avoid possible confusion with bruising, DM should always be documented when detected on physical examination. DM is benign and usually disappears during the first or second year of life, but may persist in dark-skinned individuals.

Blue nevi are uncommon benign tumors composed of dermal melanocytes that may be present at birth. The common blue nevus and the cellular blue nevus cannot be distinguished clinically but differ histologically. Blue nevi are well-circumscribed, slate blue or bluish black papules or nodules with a predilection for the buttocks, face, or dorsum of the hands and feet. Common blue nevi are usually less than 15 mm in diameter and are not a risk for the development of malignant melanoma. Cellular blue nevi are often larger and may rarely undergo malignant transformation into malignant melanoma.

Café au lait spots (CALSs) are well-circumscribed, homogenously pigmented, light brown macules that range from 1.5 to 15 cm in diameter. They are frequently present at birth, are almost always present by 1 year of age, and may increase in number during early childhood. CALSs are seen in approximately 2% of all newborn infants and up to 25% of the normal adult population. They are more common in darker-pigmented races. The vast majority of patients with CALSs have one or two lesions and have no associated abnormalities. However, the presence of six or more with a diameter of greater than 0.5 cm before puberty and 1.5 cm after puberty is highly suggestive, but not diagnostic, of neurofibromatosis. CALSs are also seen in other disorders, including tuberous sclerosis, McCune Albright syndrome, ataxia-telangiectasia, and Bloom syndrome.

Mastocytosis is an uncommon disorder characterized by the abnormal accumulation of mast cells in tissues. Mast cell disease encompasses a spectrum from isolated cutaneous involvement to systemic disease (Table 68.2). The cause for the increase in mast cell numbers is not completely understood. However, mutations of c-kit, the receptor for mast cell growth factor, on mast cells have been demonstrated. Cutaneous lesions appear as red-brown to yellow-brown macules, papules, or nodules that range in size from a few millimeters to several centimeters in diameter. Characteristically, the skin lesions will urticate with rubbing (Darier sign) because of mast cell degranulation and histamine release resulting in increased vascular permeability, edema, and wheal formation. If the edema is marked, blistering may occur. Mastocytomas are present at birth or develop shortly thereafter and appear as reddish-brown plaques or nodules. Single lesions are the rule, although occasionally two or three are present, typically involving the distal extremities, particularly the wrist. Most isolated mastocytomas resolve spontaneously after several years. Generalized cutaneous mastocytosis (urticaria pigmentosa) is characterized by the appearance of multiple red-brown macules, papules, and plaques (Fig. 68.2). The majority of cases occur before puberty, with about half presenting before 9 months of age. Most affected children have significant clearing or complete resolution of the cutaneous lesions by early adulthood. Systemic symptoms may occur because of release of histamine and other mediators from cutaneous lesions and include pruritus, flushing, hypotension, tachycardia, and, less often, diarrhea, dyspnea, and syncope. Systemic mastocytosis with mast cell infiltration of bone, liver, spleen, lymph nodes, skin, and gastrointestinal tract is rare in children.

Epidermal nevi are benign tumors in which the epidermis is hyperplastic. A variety of names have been given to this lesion, including linear epidermal nevus, nevus unius lateris, ichthyosis hystrix, and systematized epidermal nevus. Most epidermal nevi are present at birth and may become more extensive with age. The lesions are tan, brown, or black verrucous growths arranged in a linear, asymmetric fashion and are more often unilateral than bilateral. The diagnosis of epidermal nevus syndrome is made when epidermal nevi are seen in association with central nervous system, ocular, musculoskeletal, and other organ abnormalities. Inflammatory linear verrucous epidermal nevi (ILVEN) are distinguished from linear epidermal nevi clinically by the presence of pruritus and erythema and histologically by the presence of inflammation and parakeratosis. They are usually present at birth and occur mainly on the extremities in girls.

Sebaceous nevi are benign hamartomas of sebaceous and apocrine glands that present at birth on the head or neck. They are well-circumscribed, often linear, yellow-orange, smooth, hairless, verrucous plaques (Fig. 68.3). At puberty, enlargement occurs as the sebaceous glands become active under androgenic influence. Large sebaceous nevi may be associated with congenital skeletal defects and CNS disease, including mental retardation and seizures, much like those seen in the epidermal nevus syndrome. Small, isolated lesions of sebaceous nevi are not associated with other defects. During adulthood, sebaceous nevi may be complicated by secondary tumor development. Syringocystadenoma papilliferum and trichoblastomas are the most common tumors to arise from sebaceous nevi and occur in approximately 10% of the cases. Basal cell carcinomas (BCCs) were previously believed to be the most common tumors arising from sebaceous nevi. However, retrospective studies have shown that the majority of these cases were actually trichoblastomas. Because most tumors occur in adults older than age 40 and the incidence of BCC is much lower than once believed, prophylactic surgery is of unclear benefit and clinical follow-up is probably sufficient.

Piebaldism is a rare autosomal dominant disorder caused by mutations in the c-kit gene, in which depigmented patches of skin are present at birth. Characteristic features are a white forelock or hypopigmented tuft of hair in the frontal region and the presence of normally pigmented islands of skin within the leukoderma. Some affected individuals have been reported to have cerebellar ataxia, neurosensory deafness, or mental retardation. A white forelock, leukoderma, heterochromic irides and fundi, hypertelorism, congenital deafness, premature graying of hair, confluence of the medial eyebrows, and a broad nasal root are manifestations of Waardenburg syndrome. Also autosomal dominant, there are several genetic variants of this disorder that are caused by mutations of the PAX3, MITF, or ENDRB genes.

Hypomelanosis of Ito (incontinentia pigmenti achromians) is a rare disorder of irregular, linear, and whorled hypopigmentation on the trunk and extremities. Approximately three-fourths of affected individuals will have associated abnormalities of the CNS, eyes, teeth, nails, hair, musculoskeletal system, or internal organs. In most cases, the pigmentary changes are present at birth or within the first year of life and may become more extensive.

Nevus anemicus is a congenital developmental anomaly that is characterized by hypopigmented macules of varying size and shape. The involved area is lighter than the normal skin, not because a loss of pigment occurs, but because blood vessels are constricted, producing a permanent blanching of the area. This blanching is a functional rather than a structural abnormality, presumed to be caused by local increased sensitivity to catecholamines. The color difference between the nevus and the normal skin can be accentuated by brisk rubbing; the normal skin becomes red, whereas the nevus does not. A nevus anemicus is not generally associated with other defects and does not change with age.