Sarah L Chamlin

Shedding light on moles, melanoma, and the sun 

 With the alarming increase in the incidence of melanoma, pediatricians must know how to differentiate worrisome moles from benign ones, identify children at risk, and educate families about sun protection. 

 The incidence of melanoma is increasing at an alarming rate. In 1935, the lifetime risk of developing a melanoma was one in 1,500. By 1991, it had risen to one in 105. Today, melanoma occurs in approximately one in 75 persons.

 Although melanoma accounts for only 2% of all pediatric malignancies, the incidence in older adolescents has doubled in the past 10 years.

 In the United States, melanoma is the sixth most common cancer in adolescents 15 to 19 years old. Teenagers, it seems, are catching the tail of the worldwide adult-centered melanoma epidemic.

 Most risk factors for the development of melanomaincluding sun sensitivity, excessive sun exposure, numerous or atypical nevi, congenital nevi, and a family history of melanomacan be identified in childhood. Pediatricians, therefore, play a pivotal role in identifying and monitoring children at risk and in educating children and families about sun protection.

 Approximately 1% of newborns are born with a congenital nevus. Congenital nevi are categorized according to their estimated adult size: large (greater than 20 cm), intermediate (between 2 cm and 20 cm), and small (less than 2 cm). Congenital nevi are often larger than common acquired nevi, more likely to have a papillated surface, and frequently develop hair within them (Figures 1 and 2). In some newborns, congenital nevi are light brown and flat and may be difficult to distinguish from café-au-lait patches until they thicken and darken with time. Some nevi that appear later in childhood are indistinguishable from congenital nevi clinically or histologically and are considered congenital nevus-like nevi.

 While only 1% of newborns have congenital nevi, 6% to 12% of children and adults have congenital nevus-like nevi, and 20% of adults report this type of nevus present since childhood.

An increased risk of melanoma has been ascribed to congenital nevi, although the magnitude of this risk is uncertain. Early assessments of melanoma risk in congenital nevi (between 2% and 15%)

 were overestimates because they did not take into account the prevalence of congenital nevus-like nevi in the population.

 Although the risk for the development of melanoma is likely at the low end of these early estimates, the occurrence of melanoma in congenital nevi is well documented, and these nevi need to be assessed and monitored for atypical features and changes. Features of concern include development of an off-center nodule or papule, color change within a portion of the nevus, bleeding, persistent irritation, erosion, ulceration, and rapid growth. Some changes in congenital nevi are considered normal and physiologic, including uniform darkening and the development of hair.

Therapy should be individualized according to age, race, site of the nevus, and other risk factors.

 Deeply pigmented or nodular lesions may require excision because of the difficulty in assessing clinical change. Congenital nevi in African-American children and other deeply pigmented races are low-risk lesions and in most instances do not need to be excised.

 Congenital nevi should be followed annually for clinical change. If excision is recommended, it can often be delayed until the child is old enough to tolerate a procedure under local anesthesia.

Congenital nevi exceeding 20 cm in size (giant or large) are rare and occur in less than one in 20,000 infants. They are most commonly found on the trunk but can occur in any location. Smaller "satellite" nevi may be present at birth or can appear later in life. Neurocutaneous melanosis, a melanocytic proliferation within the leptomeninges or brain parenchyma, occurs in approximately one fourth of children with a giant congenital nevus overlying the head or spine.

 Although symptomatic neurocutaneous melanosis is rare, children with giant congenital nevi should be evaluated for central nervous system (CNS) involvement with gadolinium-enhanced magnetic resonance imaging when the nevus is present on the scalp or over the spine.

The risk of melanoma in giant nevi is estimated to be 5% to 15%.

Melanoma can arise from the nevus itself or from extracutaneous sites such as the CNS. Satellite nevi have not been associated with malignancy. Ideally, a team of physicians that includes a pediatrician, dermatologist, and plastic surgeon should care for infants with giant nevi. Close clinical follow-up for early detection of melanoma is required and total or partial excision of the nevus is recommended when feasible.

Appearing early in childhood, common acquired nevi reach their maximal number by 20 to 30 years of life, and tend to disappear with age. This type of nevi is small (less than 5 mm) and evenly pigmented with sharply demarcated borders, and predominates in sun-exposed areas. Common acquired nevi can be junctional (a pigmented macule), compound (a pigmented papule), or intradermal (a skin-colored papule).

 The number of common acquired nevi present on a person is determined by many factors including sun exposure, skin type (Table 1), and genetics (Figure 3). Intense sun exposure during childhood is associated with increased mole counts. Lightly pigmented skin types have high mole counts, and darkly pigmented skin types have low mole counts.

Monozygotic twins have similar mole counts, suggesting a role for genetics.

 In addition, immunosuppressed children may develop an increased number of nevi.

 Melanoma risk increases with high mole counts, suggesting that aggressive sun protection in infancy, childhood, and adolescence may reduce this risk.

 Dysplastic or Clark's nevi, as atypical nevi are also known, are often larger than common acquired nevi, have irregular or poorly defined borders, and have variable pigmentation (Figure 4). They frequently occur in persons with a high mole count.

 Although an increased number of nevi and atypical nevi are both risk factors for melanoma, the presence of atypical nevi may be a more important risk factor for melanoma than the number of nevi alone.

 Children with an increased number of common acquired nevi should be closely monitored for the development of atypical nevi. As a rule, preadolescent children should have less than 15 common acquired nevi; more than this number may indicate the "atypical mole" phenotype. Most often, atypical nevi appear during adolescence. Of note: Not only can existing atypical nevi transform into a melanoma; melanoma can arise de novo. Routine full-body examination is indicated in children with atypical nevi, an increased number of nevi, and a family history of melanoma. Suspicious or changing lesions should be referred for evaluation by a dermatologist (Table 2 in the print edition, adapted from Chamlin SL, Williams ML: Pigmented lesions in adolescents. 

Adolescent Medicine: State of the art Reviews

Some children and adolescents with multiple common acquired nevi and multiple atypical nevi are difficult to accurately evaluate for new or changing nevi because of the vast number of nevi. Full-body photographs are an invaluable tool for evaluating nevi in older adolescents and adults, but are less useful in young children because the development of new nevi and changes in existing nevi are most often normal events.

Children with multiple atypical nevi and family members with atypical nevi and melanoma may be affected by the autosomal dominant, familial atypical mole and melanoma syndrome. Two genes that predispose to melanoma have been identified in such familiesCDKN2A (on the short arm of chromosome 9) and CDK4 (on the long arm of chromosome 12).

 Familial melanoma occurs at a younger age, with 10% of affected persons experiencing their first melanoma in childhood.

 A higher frequency of multiple melanoma lesions is seen with this syndrome than with nonfamilial melanoma. Children with a family history of melanoma require early careful monitoring for suspicious lesions.

 A few other types of nevi deserve special attention. A 

 is usually a smooth, pink to brown, dome-shaped papule (Figure 5). This nevus is more common in children than in adults and often occurs on the head and neck. All Spitz nevi do not need to be excised, but complete excision should be considered for large, rapidly growing or changing lesions. Although, histologically, these nevi appear similar to melanoma, in most cases architectural features differentiate them. If a Spitz nevus is incompletely excised and recurs, histopathologic differentiation from melanoma can be difficult. Although a Spitz nevus is considered benign, lymph node metastasis has been reported in pediatric patients.

 is a pigmented nevus surrounded by a ring of depigmented skin (Figure 6). This immune reaction to the nevus eventually results in its eradication over months to years. Halo nevi are a common finding in children and adolescents. Although these nevi are usually of no significance to pediatric patients, a melanoma at a distant site can trigger this type of immune response, and a careful, full-body examination for suspicious lesions is indicated for patients with halo nevi. A more common association than melanoma in children with halo nevi is vitiligo.

, or speckled lentiginous nevus, is a solitary light brown patch (1 to 20 cm in diameter) with multiple darker brown or brown-black papules within it (Figure 7). This nevus can be congenital or acquired and occurs in 2% to 3% of adults.

 Nevi spili have the potential to develop melanoma and routine follow-up is advised. Because of the speckled appearance and difficulty in detecting change, nevus photographs may be helpful.

 is a type of intradermal nevus with heavily pigmented melanocytes (nevus cells) deep within the skin. Blue nevi may be present at birth, but more commonly appear later in life as blue, well-demarcated papules or nodules (Figure 8). Melanoma can develop in a blue nevus and excision is required for a rapidly changing or growing lesion.

Pigmented lesions involving the nail unit

 pose a challenging situation. The differential diagnosis of a pigmented band in a nail includes a nevus, nail trauma, infection, drug-induced causes, and benign longitudinal melanonychia. The latter is commonly seen in darkly pigmented races and occurs in 60% of African-Americans more than 20 years of age.

 Although melanoma is uncommon in African- Americans, 20% of melanomas in this population involve the nails. When all races are considered, only 2% to 3% of melanomas involve the nail. Nail melanoma is exceedingly rare in children, but a nail matrix biopsy is indicated for an enlarging or irregularly pigmented band, particularly if the proximal nail fold (cuticle) is also pigmented (Hutchinson's sign).

 In preadolescent children, melanoma is most often the nodular type and presents as a rapidly growing lesion with bleeding or itching. It may present as a subcutaneous nodule or localized lymphadenopathy. In older children and adolescents, melanoma presents as an enlarging or changing pigmented lesion with irregular color or borders. These features are characteristic of superficial spreading melanomas (Figure 9).

Melanoma most commonly occurs in sites of intermittent intense sun exposure and sites of previous sunburn. In men, truncal melanoma is more common; in women, lower extremity melanoma. This anatomic distribution is similar for adolescents with melanoma.

Numerous nevi, atypical nevi, and a family history of melanoma are strong predictors of melanoma risk in children.

 The strongest risk factor associated with melanoma in adolescents in one recent case-control study was the presence of more than 100 nevi 2 mm or greater in size. Other reported risk factors include red hair, blue eyes, inability to tan after sun exposure, and heavy facial freckling.

 Although melanomas occurring in giant congenital nevi during childhood are well documented, they account for only 3% of pediatric melanomas.

 Clinically, melanomas are often larger than benign nevi. Pigmentation is often irregular with shades of brown, blue, black, red-purple, or gray, and borders are irregular or notched. The ABCD signs of melanoma can help in identifying atypical nevi and melanomas (Table 3). Off-center nodules, pruritus, ulceration, and bleeding are also potential signs of melanoma. In a child with multiple nevi, it is useful to assess if one lesion stands out from its neighbors (the "ugly duckling sign").

 In an adult, growth of an existing nevus is a sign of malignancy, but in a child growth is expected as skin surface area increases. Growth of nevi, change in existing nevi, and the appearance of new nevi in children challenge the pediatrician and dermatologist to differentiate physiologic changes from malignant change. The ABCD signs of melanoma may be helpful in this regard.

The survival rate for melanoma in children and adults seems to be the same, with tumor thickness and depth of invasion the primary determinants of prognosis. Brain metastasis occurs in approximately 18% of children with melanoma and is associated with a poorer prognosis.

 Some series report a poorer prognosis for melanoma in children than in adults, possibly because of a delay in diagnosis.

 This delay may be attributed to the rarity of pediatric melanoma, the difficulty in evaluating change in pediatric pigmented lesions, and the relative reluctance to biopsy children.

Surgical excision is the first step in the management of melanoma. Commonly, surgeons perform a conservative excision with narrow margins followed by a wider excision; margin size is dictated by the depth of melanoma invasion. Staging with a sentinel lymph node dissection is often performed for high-risk melanomas. This technique involves an injection of a radiolabeled dye at the site of the melanoma. The dye is traced to the lymph node bed and the node(s) first labeled are removed. This procedure is associated with lower morbidity than an elective lymph node resection, which involves a more radical removal of the lymph node bed. Therapy of advanced melanoma may include chemotherapy, radiotherapy, and immunotherapy. Adjuvant therapy with high-dose interferon alfa-2b is indicated for patients with high-risk melanoma; data suggest improved relapse-free and overall survival.

Excessive childhood sun exposures, sunburn, and sun sensitivity increase melanoma and non-melanoma skin cancer risk. Our best defenses against the sun are avoidance, protective clothing, and sunscreen and sunblock. Although concerns have been raised that sunscreen is not protective against melanoma, use of sunscreens is, in fact, an important defense against the sun. The controversy has arisen for several reasons. In the past, most sunscreens protected the skin mainly from UVB light, not UVA light, which is implicated in the pathogenesis of melanoma. UVA light is able to produce melanoma in fish, but the wavelength of light that produces melanoma in humans is uncertain.

 In addition, the use of sunscreens may instill a false sense of security and result in longer time spent in the sun, which may increase rather than reduce skin cancer risk.

 Sunscreen and sunblock with broad-spectrum protection from both UVB and UVA light should be recommended for use in children. But the use of these products does not give our patients carte blanche to spend the day in the sun. In addition, other protective measures are required, including protective clothing and avoidance of peak sun hours (see the 

Despite the recent increase in public awareness and regular use of sunscreen, the melanoma rate continues to rise. It will be decades before the impact that sun safety measures have on the incidence of melanoma can be measured. Regrettably, changes in behavior lag far behind awareness of risk, with suntans still viewed as a sign of health to many. The difficulty in changing public behavior and perception and the perceived "invincibility" of teenagers (and their desire to fit in) pose a real challenge for pediatricians and dermatologists. An estimated 80% of lifetime sun exposure occurs before the age of 21 years, and it is estimated that regular use of sunscreens in the first 18 years of life could reduce the lifetime incidence of all skin cancers by 78%.

 Broad-spectrum sunscreen use may be associated with the development of fewer nevi, particularly in freckled children.

 Decreasing the mole count (an important melanoma risk factor) in this fashion may have an impact on one's ultimate melanoma risk.

 Sun safety should begin in infancy and should be included in discussions of risk behaviors, including smoking and seatbelt use for teens.

 Sun safety education, through the combined efforts of pediatricians, dermatologists, the media, and schools, may help bring the melanoma epidemic under control.

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Pediatricians must know how to differentiate worrisome moles from benign ones, identify children at risk, and educate families about sun protection.