Pediatric Dermatology

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Important Melanocytic Lesions in Childhood and Adolescence Monique E. Roth, MD, * and Jane M. Grant-Kels, MDt

Melanocytic nevi are common in both children and adolescents and are generally benign. Some melanocytic lesions, however, are of concern because of their malignant potential or because of the difficulty in differentiating them from malignant melanoma. These lesions may present both clinical and histopathologic challenges, and several have been the source of considerable controversy. The clinical manifestations and management in children of common acquired melanocytic nevi, congenital nevi, dysplastic nevi, Spitz nevi, and malignant melanoma are reviewed in this article. COMMON ACQUIRED MELANOCYTIC NEVI Recent interest in banal acquired melanocytic nevi has been inspired by the recognition of these common lesions as potential markers of increased melanoma risk. Acquired nevi are generally first noted during infancy as minute tan macules. 21 Melanocytic nevi increase steadily in number throughout childhood, adolescence, and young adulthood. 42, 106 A British stud y137 of 187 children noted a statistically significant increase in the number of nevi present between the ages of 8 and 9. Grob et al 55 determined that 82% of individuals over 18 years of age had more than 10 nevi. Similarly, Holly et also found that 81 % of individuals from 20 to 74 years of age had more than 10 nevi. Clinical and histologic evolution of nevi occurs with aging, characteristically with progression from predominantly junctional nevi during childhood and adolescence, to compound nevi in young adulthood, and finally, to intradermal nevi in older individuals. 21 In later years, common acquired nevi typically regress,21, 49, 85 with many individuals over 71 years of age shOWing no nevi. 85 Increasing evidence exists that the presence of numerous banal com*Resident, Division of Dermatology, Brown University, ProVidence, Rhode Island tChief, Division of Dermatology, Director of Dermatopathology, Associate Professor of Medicine, and Assistant Professor of Pediatrics and Pathology, University of Connecticut Health Center, Farmington; and Clinical Instructor in Dermatology, Yale University, New Haven, Connecticut

Pediatric Clinics of North America-Vol. 38, No.4, August 1991

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mon acquired nevi represents a marker for individuals at increased risk of melanoma. A recent case control study showed nevus counts to be a better predictor of melanoma risk than sun exposure and such phenotypic traits as hair color, complexion, and propensity to sunburn. 55 The largest risk was associated with the presence of nevi considered by the investigators to be without evidence of clinical atypia but were fairly large (5-10 mm in diameter). A significant, but lesser, risk was associated with large numbers of small (1-5 mm) nevi. In a 1989 case control study, MacKie et a185 also found that the number of nevi present was the most important of the melanoma risk factors investigated; a tendency to freckle, presence of atypical nevi, and episodes of sunburn were other independent, but less powerful, predictors of melanoma risk. Likewise, Holly et a160 found a relative risk of melanoma of 1.6 for individuals with 11 to 25 nondysplastic nevi, 4.4 for those with 26 to 50 such lesions, and relative risks of 5.4 and 9.8, respectively, for patients with 51 to 100, and more than 101 banal nevi. Other investigators have also found a significantly increased risk of melanoma associated with large numbers of nevi. 47 . 61 Several studies have suggested that factors that have been implicated in the development of melanoma are instrumental in the generation of nevi during childhood. In a study of 211 Australian schoolchildren, male sex, pale skin, and nonblack hair showed independent statistically significant association with increased numbers of raised nevi. 48 In a study of 187 8- and 9-year-old British children, pale skin color and family history of skin cancer correlated with number of nevi. 137 Rampen et aP06 found that mole counts were higher in light-complexioned children and young adults and that the anatomic distribution of nevi in all age groups corresponded to the anatomic distribution of melanoma in adults, with women demonstrating more numerous nevi on the lower legs and men demonstrating a preponderance of nevi on the back. Similarly, in a study involving 1146 Canadian children 6 to 18 years of age, anatomic distribution of nevi in adolescents roughly paralleled the distribution associated with melanoma in the adult population, with men showing higher numbers of nevi on the head, neck, and trunk and women showing increased nevi on the limbs. 42 Nevi in adolescents and in younger children were most frequent in intermittently sun exposed areas, less frequent in maximally exposed areas, and least frequent in minimally exposed areas. 42 Further data gathered on 913 of these children revealed significantly higher numbers of nevi in children with a tendency to sunburn rather than tan and in those with a history of frequent or severe sunburn. 43 These investigations support other epidemiologic evidence62 • 82 that interventions aimed at the prevention of melanoma must be instituted in early childhood.

CONGENITAL NEVI Melanocytic nevi are present on the skin of 1% to 2% of newborns. 4. Most of these congenital nevi are small. The frequency of giant congenital nevi ranges from 1 in 11604 in a series involving 4641 newborns in the United States, to 1 in 20,500 of a series of 532,831 South American 79. 120. 147

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newboms. 17 Although it is generally agreed that individuals with giant congenital nevi are at increased risk for the development of melanoma, 83, 104, lOS, 117 the risk associated with small and medium size congenital nevi has remained controversial. 3, 25, 32, 63, 70, 114, 115, 136 Relevant studies have been hampered by methodologic problems, including differing standards for classifying nevi based on size and lack of specificity of the histopathologic criteria used in identifYing nevi as congenital. 25,26, 70, 118 The criteria for classification of a nevus as giant have varied between studies. Definitions of giant congenital melanocytic nevi (GCMN) have included lesions large enough that they cannot be excised and closed primarily in a single procedure,s, 80 those with a diameter of more than 20 cm,70 and those with a diameter more than the size of the individual's palm if the lesion is on the head or neck, or twice this size if elsewhere on the body. 83 Clinically, GCMN are characterized by a medium to dark brown color, a verrucous or lobulated surface, 5 and coarse terminal hair growth. III GCMN frequently show peripheral satellite nevi (Fig, 1).5 Darkening of the lesion and increased surface irregularity often develop as the child ages. 5 The largest of these lesions are often described as being garment-like in their anatomic distribution. lOS, 117 The psychosocial impact of these lesions on the affected individual can be substantial. 44 GCMN involving the scalp and neck may be associated with leptomeningeal melanocytosis, resulting oc-

Figure 1. Child with a giant congenital melanocytic nevus and smaller satellite congenital nevi.

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casionally in development of hydrocephalus, seizures, and rarely, in the development of leptomeningeal melanoma. 12. lOS Despite the relative rarity of GCMN, most large reported series of children with melanoma include children in whom malignancy developed in such a lesion (Fig. 2).6,36, 81, 131, 144 In 1974, Kaplan64 reported seven cases

Figure 2. A and B, Newborn with a giant congenital melanocytic nevus showing prenatal development of malignant melanoma. (From Schneiderman H, Wu AY, Campbell WA, et al: Congenital melanoma with multiple prenatal metastases. Cancer 60:1371-1377, 1987; with permission. )

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of melanoma arising in large congenital nevi and provided a review of the literature that demonstrated a collective average risk of 14%. In 1987, however, Kaplan and NickolofP'5 noted that many clinical reviews, including their own earlier work, were flawed by selection bias for larger lesions and those in which melanoma had already developed, because these lesions are more likely to be referred to academic centers. In a review of 151 Danish patients with GCMN, Lorentzen et al83 calculated a 4.7% lifetime risk of melanoma. The late age of enrollment in this series, at a mean age of 8 years, probably led to an underestimation of risk by excluding those patients in whom fatal melanoma developed in early childhood. In Kaplan's 1974 review of the literature,64 60% of melanomas developing in individuals with GCMN occurred in the first decade of life. Rhodes et al ll7 recalculated a lifetime risk of melanoma of 6.3% in patients with GCMN using the data of Lorentzen et al. 83 Based on a series of 39 patients followed for a mean of 8.64 years, Quaba and Wallace lO4 calculated a melanoma risk of 8.52% during the first 15 years of life. A prospective study based on a registry of patients with congenital nevi more than 20 cm, which was established in 1979, will clarify the magnitude of risk of melanoma in these individuals. 44 Because of the high risk of malignant degeneration during childhood, the early excision of GCMN has been recommended. In 1981, Rhodes et al ll7 estimated the risk of death caused by general anesthesia during the first year of life to be considerably less than the risk of development of melanoma during the same period. Kaplan and NickolofI05 also recommend removal of GCMN during early infancy. They generally initiate surgical resection at the age of 3 to 6 months, with 6- to 9-month intervals between procedures if multiple surgeries are required. 65 Because the site of development of melanoma within GCMN can be nonepidermal, ll7 excision to the level of the subcutaneous tissue is preferred. 65 This objective may by necessity be compromised in areas where such excision would result in diminished function. 65 Development of melanoma beneath a skin graft at a site at which a giant congenital nevus had been excised to the superficial aspect of the subcutaneous fat has been reported. ll7 Decisions regarding excision of GCMN are complex, requiring evaluation of cosmetic, psychosocial, and functional considerations, as well as risk of malignant degeneration. 65 Small congenital melanocytic nevi (SCMN) are considerably more common than GCMN4 and are, therefore, of potentially greater epidemiologic significance if they represent precursors of melanoma. The risk associated with SCMN, however, remains controversial. Rhodes et al 1l5 found histologic features of congenital nevi to be present in 8.1% of 234 melanoma specimens. Rhodes and Melski 1l4 calculated the relative risk associated with SCMN by comparing the frequency of SCMN at the site of subsequently diagnosed melanoma with the statistical occurrence of histologically confirmed melanocytic nevi in newborns. A 21-fold increase in the risk of melanoma was estimated in individuals with SCMN when the presence of a congenital nevus at the site of melanoma was determined by patient history. A three to ten fold increase in risk of melanoma was associated with SCMN when the presence of SCMN at the site of devel-

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opment of a melanoma was determined histologically.114 Interpretation of such data is complicated by the lack of specific histologic criteria for the identification of SCMN 25, 26, !1S and the unreliability of patient history regarding the congenital nature of lesions. 25 The risk of melanoma associated with medium sized melanocytic nevi has not been thoroughly addressed. Some investigators have recommended the excision of all congenital nevi, citing risk of malignant degeneration and the low risk associated with the excision of small lesions under local anesthesia. 3, 113, 136 Others have argued against routine removal of SCMN, noting insufficient evidence of increased risk of melanoma25, 70 and the impracticality of devoting thousands of hours each year to the excision of these common lesions. 70 A 1984 consensus conference concluded that there were insufficient data to recommend prophylactic excision of all congenital nevi. 38 Elde~2 suggested that observation is a reasonable alternative to excision and that patients may be offered this option. He noted, however, that life-long follow-up of SCMN is more expensive than excision at the first visit. Among authors who recommend the prophylactic excision of SCMN, it is generally agreed that surgery need not be performed in early childhood. 63, 114 Illig et al 63 noted that in contrast to GCMN, the risk of melanoma associated with SCMN occurs primarily after the age of puberty. Rhodes and Melski 114 state that if follow-up is adequate and the lesion is without features suspicious for development of melanoma or features that would make detection of melanoma difficult, excision may be delayed until the child is old enough to cooperate with a procedure performed under local anesthesia. Although development of melanoma in SCMN is generally of epidermal origin and therefore relatively easily detected on examination, malignant melanoma developing from the dermal component of a SCMN in the absence of detectable change in surface pigmentation has been reported. 130

DYSPLASTIC NEVI The clinical and histopathologic features of the familial dysplastic nevus syndrome, initially designated the B-K mole syndrome, were first described by Clark et aP3 in 1978. Family members who inherit this autosomal dominant trait8, 10, 53, 84 have a phenotype characterized by atypical nevi and are at high risk for the development of melanoma. 23. 51, 52, 74, 109 Following the description of dysplastic nevi (ON) in the familial melanoma setting, the occurrence of clinically and histologically indistinguishable ON in individuals with nonfamilial melanoma was reported. 34 It was soon recognized that similar lesions may develop in individuals without melanoma. 28, 105 Such sporadic ON have been estimated to affect 7%93 to 9%56 of the population. In these individuals, ON may be markers of increased melanoma risk. 33, 56, 60. 75. 78. 93. 116, !19, 126 The importance of ON as markers for increased risk of melanoma outside of the familial melanoma setting remains controversial. AnalysiS of available data regarding these lesions is complicated by the use of differing histopathologic criteria for their diagnosis. 1, 20. 40, 118, 127 The detection in

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some investigations of a high frequency of DN in the general population has led to questions regarding the importance of these lesions in the epidemiology of melanoma. Piepkorn et aPOl detected clinically atypical and histologically dysplastic nevi in 20% of a white population. They estimated the prevalence of persons with histologic dysplasia in at least one of two biopsied nevi to be 53% of a white population. A recent study noted histologic features associated with DN in 87.8% of clinically benign nevi when cytologic atypia was not required for the diagnosis. 69 When cytologic atypia was required, changes believed to be diagnostic of DN were found in 29.3% of clinically benign appearing nevi. 69 A classification system proposed by Kraemer et aF5 is useful in conceptualizing the occurrence of DN in various groups of individuals. Type A dysplastic nevus syndrome (DNS) is comprised of individuals with , DN, but without melanoma and without family members with DN. In Type B DNS, DN are present in two or more family members, but there is no history of melanoma within the kindred. An individual with both DN and melanoma but without either present in family members represents Type C DNS. Type D DNS includes kindreds in which both familial dysplastic nevi and familial melanoma are present; it is further subdivided into Type D-1, in which only one family member has had DN and melanoma and Type D-2, in which at least two family members have had both melanoma and DN. The estimated 32,000 individuals 75 with DN who are members of D-2 kindreds have an extremely high risk of melanoma. 52. 73. 75 In affected individuals, the probability of melanoma developing between the ages of 20 and 59 is 56%.52 Thirty percent of such patients develop more than one melanoma over the course of their lives. 52 The median age at the time of diagnosis of a first melanoma in affected individuals is 35 years for men and 29 years for women. 52 Melanoma developed before the age of 20 years in 10% of 67 D-2 family members with melanoma.145 Reports have included children in D-2 families who developed melanoma at 10145 and 12 years of age. 52 As noted, the risk associated with DN outside of the familial melanoma setting remains controversial. In a recent case control study, the odds ratio for development of melanoma in individuals with sporadic DN was calculated to be 3.7. 56 Clinically, dysplastic nevi differ from common acquired nevi by their larger size (frequently 5-10 mm in diameter), common presence on the trunk and buttocks, and their continued development throughout life. 23, 74 Lesions may number from very few to more than 100. 23, 74 The clinical appearance of DN is the same in both sporadic and familial forms. Lesions are variegated in color, with shades of tan, brown, and pink, and often have an indistinct and irregular border (Fig. 3).23, 74 They are frequently macular74 or show a dark central papule surrounded by a lighter macular periphery,39 The surface may show a cobblestone appearance. 39 Development of melanoma within a DN is often associated with the appearance of a new black area within the lesion. 52. 74 In affected patients, however, melanoma may develop de novo at a site uninvolved by DN,40 Dysplastic nevi serve, therefore, not only as precursors of melanoma, but as markers of increased risk.

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Figure 3. Cluster of three dysplastic nevi on the trunk of a child. (Courtesy of R. Friedman, MD.)

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The care of individuals with DNS is focused on the prevention and the early detection of melanoma. Education of patients is central in encouraging self examination and medical follow-up, as well as in promoting such risk-altering behavior as avoidance of sunburn. The effectiveness of such surveillance in facilitating the early detection of melanoma in D-2 DNS families has been demonstrated. 88 When a patient who is not known to belong to a D-2 family is diagnosed with melanoma or with DN, an attempt should be made to examine first degree relatives, as well as an inquiry made regarding a family history of melanoma. Such an approach will assist in establishing the degree of risk associated with DN in the patient and may result in the early detection of melanoma in family members.2 Children with familial DNS characteristically are without unusual pigmented lesions during infancy and early childhood, so. 73. 145 but frequently develop an increased number of morphologically normal nevi between 5 and 9 years of age. 145 Typical dysplastic nevi often first appear as the child reaches puberty.73. 145 The scalp is not infrequently the earliest site at which clinically and histologically dysplastic nevi occur. 145 There are limited data available regarding the management of DN during childhood. A recent symposium has addressed some of the issues involved in the diagnosis and care of affected children. 125 The optimal frequency of follow-up for such patients has not been established. Many recommend annual examination of prepubescent D-2 family members who are without unusual nevi. 125 Examination before the age of 5 or 6, however, is likely to be unrevealing. 50 Preadolescent family members with dysplastic nevi are commonly followed at 6-month intervals, although various authors

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recommend a follow-up examination ranging from 3-month to yearly intervals. 125 Increased frequency of surveillance may be advisable at puberty and during the late teens and early twenties, because these ages are frequently associated with acceleration in the appearance of new nevi and with changes in existing nevi. 50 0-2 family members who do not demonstrate dysplastic nevi by the late teens or early twenties generally remain unaffected. 50 Optimal follow-up of postpubescent patients with dysplastic nevi but without a significant family history has not been established. These patients are commonly followed at 6-month to yearly intervals. 125 Although some authors have recommended routine excision of one or two lesions for histologic confirmation, 19 others have recommended that the diagnosis of dysplastic nevi be made on a clinical basis and biopsy be performed only if a lesion is suspicious for the development of melanoma. 125 Because of the difficulty involved in monitoring scalp nevi, some investigators have advocated excision of all ON occurring in this location 145; others, however, do not recommend the routine removal of such lesions. 125 Photography has been advocated as a means of monitoring patients with dysplastic nevi for new and changing lesions. 19. 71. 132 Centers specializing in pigmented lesions frequently perform total body photographs of affected patients, with close-ups of particularly atypical lesions. 132 Although the need for photography has been questioned based on the expense involved,27. 107 it has been argued that such documentation is cost effective because it helps avoid l,mnecessary biopsies. 72 In adults, the removal of all new or changing nevi has been recommended. 19 In preadolescent children, the use of whole body photographs is complicated by the expected increase in number of nevi as the child ages, making excision of all new lesions impractical and unwarranted. l25 In children with a limited number of lesions, close-up shots of particularly atypical nevi may be helpful.

SPITZ NEVI

The significance of Spitz nevi (nevi of large spindle and/or epithelioid cells) derives mainly from the difficulty that may be encountered in differentiating these benign lesions from malignant melanoma. Prior to Spitz's description in 1948 of histopathologically distinct lesions that she termed juvenile melanoma,138 malignant melanoma was believed to behave in a benign manner in children. 97 As a result of misdiagnosis of Spitz nevi as malignant melanoma, earlier literature overestimated the incidence of malignant melanoma in children and underestimated the mortality rate associated with it. 87. 128 Although Spitz nevi may occur at any age, most occur in children and young adults. 98, 100, 148 These lesions have been estimated to constitute considerably less than 1% of melanocytic nevi occurring in children. 98 Although more frequently reported in white children, Spitz nevi may also be seen in black children. 16 Most reviews have found the head, neck, and lower extremities to be the most frequent site of these lesions, although the trunk and arms are not uncommon locations. 98, 100 As is the case with

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malignant melanoma, change in color or size of a given lesion is a frequent presenting complaint of patients with Spitz nevi. 100 Clinically, Spitz nevi are generally less than 6 mm in diameter,l48 show a smooth surface,98 and are frequently dome-shaped (Fig. 4),98 although they may occasionally be polypoid98. 148 or Hat. 148 Spitz nevi are often red or pink, although tan, brown, and black lesions may be seen. 98. 100 Although they are usually solitary, multiple agminate lesions46 and, rarely, eruptive, widespread Spitz nevp33 have been reported. Although the histopathologic features of Spitz nevi may resemble those of malignant melanoma, the two can usually be differentiated. 98 Occasional lesions, however, remain diagnostic dilemmas. 94• 98 In some cases, lesions initially diagnosed as Spitz nevi have metastasized, leading to reclassification of the lesion as a malignant melanoma. 45. 94. 100 If incompletely excised, Spitz nevi occasionally recur. 96. 140 Such a recurrence is apparently uncommon; a recent report66 noted no recurrences after excision of Spitz nevi in a series of 49 patients, including 24 cases in which the lesions had been incompletely excised. Because recurrent lesions may present an even more ambiguous histopathologic appearance, however, conservative reexcision of incompletely excised Spitz nevi has been recommended. II2

MELANOMA IN CHILDREN Although melanoma is considerably more common in adults, it does occur in children. Approximately 2% of melanomas occur in patients younger than 20 years of age. 6 The incidence of melanoma increases steadily with age and it occurs seven times more frequently in the second decade of life as in the first.6 The annual incidence of melanoma in a US study was estimated to be 0.8 cases per million in the first decade oflife and 6.3 cases per million in the second decade. 6 A recent study noted an incidence of

Figure 4. Dome-shaped Spitz nevus on the cheek of a child.

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0.6 melanomas per 100,000 German children below the age of 15 years between 1981 and 1983. 99 Although melanoma may occur in children without known predisposing conditions,91 it is possible to identifY children who are at increased risk. 124 These children include those with giant congenital nevi and familial dysplastic nevus syndrome, as already discussed. Xeroderma pigmentosum, a rare hereditary disorder characterized by defects in the repair of ultraviolet-induced DNA damage,24. 76,122,123 is also associated with development of melanoma during childhood. 77, 143 Pigmentary traits such as fair skin and a tendency to sunburn are risk factors for melanoma in adults,35, 41, 47, 61, 62 although their contribution to development of melanoma during childhood is unknown. Solar exposure has been implicated as an etiologic factor in the development of melanoma. 31 , 47, 62, 86, 134 Sun exposure and sunburn during childhood62,82 and during the teenage years 149 have in particular been shown to be associated with development of melanoma in adulthood. Although the contribution of sun exposure to development of melanoma during childhood is unknown, the strong association of sun exposure during youth with melanoma in adulthood underscores the need for early initiation of avoidance of excessive sun exposure. Immunodeficient children may also be at increased risk for development of melanoma. Evidence of the prominent role of the immune system in the biology of melanoma includes the occasional spontaneous regression of metastatic melanoma, prolonged periods between excision of a primary melanoma and the development of metastases, and the effectiveness of immunotherapy in some patients. 15 An increased risk of melanoma has been reported in adults with Hodgkin's disease, 146 in renal transplant recipients, 54 and in children with genetic immunodeficiency syndromes. 50 The sudden, eruptive appearance of numerous dysplastic nevi has been reported in a 12-year-old child after renal transplantation and immunosuppressive therapy9 and in the setting of human immunodeficiency virus (HIV) infection. 3O Association of HIV infection with both eruptive dysplastic nevi and changes in a large congenital nevus has been reported in a lO-year-old boy. 30 Although rare, melanoma may be present at birth. 57, 95, 129, 141, 142 In several cases melanoma has developed prenatally in a giant melanocytic nevus. I29, 141, 142 (see Figs. 2 and 3). Extensive prenatal metastasis, 57, 142 including metastasis of fetal melanoma to the placenta,129 has been reported. Although it is a very uncommon event, transplacental metastasis of melanoma from mother to fetus has also been reported. 14, 18, 29, 59, 102 In other cases, metastasis of maternal melanoma to the placenta without apparent involvement of the fetus has occurred. 37, 102, no, 139 As in adults,7, 13, 22 the prognosis of melanoma in children depends on the level and depth of invasion of the tumor. 57, 81, 91, 92 Skov-Jensen et al131 reviewed the literature on melanoma in children and calculated that the 3-. year survival rate of children with regional lymph node metastases approximated the expected 5-year survival rate in adults. They proposed that the poorer prognosis was caused by delayed diagnosis of melanoma in children. 131 Others have reported 5-year survival rates of 33% to 34% in

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children with metastatic melanoma. 81 • 144 In a series of 25 patients younger than 20 years of age, a delay in diagnosis ranging from a few months to 5 years occurred in 60%, most often as a result of failure of a physician to recognize the malignant nature of the lesion. 91 The clinical and histopathologic features of melanoma in children are similar to those occurring in adults. As in adults, any change within a pigmented lesion is of concern. 135 Clinical findings suggestive of melanoma include an increase in the size of a melanocytic nevus, variegation in color, asymmetry, and an irregular surface (Fig. 5).67 Advanced melanomas may show ulceration, bleeding, and satellite lesions. 67 In order of decreasing frequency, the common presenting complaints of children younger than 12 years of age with melanoma are increase in size, bleeding or color change of a nevus, subcutaneous mass, pruritus of the involved lesion, and lymphadenopathy.12 In adolescents, common presenting signs and symptoms were found to include a change in the size (55%) or color (23%) of a nevus as well as bleeding (35%) or pruritus of the lesion (15%).11 Other manifestations at presentation included lymphadenopathy in 7% of patients, subcutaneous mass in 6%, and pain in 4%.11 In the case of leptomeningeal melanomas, central nervous system symptoms such as headache and ataxia are common presenting features. 12 Therapy for melanoma in children is based on experience with melanoma in adults and is primarily surgical. 91 • 92. 103 Unless contraindicated by

Figure 5. Superficial spreading melanoma with characteristic variegation in color, asymmetry, and border irregularity. (From Ross DM, Grant-Kels JM: Significant melanocytic lesions in infancy, childhood and adolescence. Dermatol Clin 4:29-44, 1986; with permission.)

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the size of the lesion or by its location, an excisional biopsy with narrow margins should be performed. 67, 92 The area may be reexcised after the diagnosis of melanoma has been established, with margin width based on the thickness of the lesion. 58 Unless extensive metastatic disease is present, clinically suspect regional lymph nodes should be resected. 58, 67 Elective regional lymph node dissection in the absence of clinically involved nodes remains controversial but is most likely to be of benefit with melanomas from 1.5 to 4.0 mm thick. 58 The most effective single chemotherapeutic agent for use in metastatic melanoma is DTIC (dimethyl triazeno imidazole carboxamide). Response rates are rather low, however, and responses are generally partial and of short duration. 58 As in adults, chemotherapy has for the most part been associated with poor responses in children. 91, 103 Prolonged survival after chemotherapy with cyclophosphamide, vincristine, and dactinomycin in children with metastatic disease has been reported. 57 In adults with melanoma, adjuvant chemotherapy to prevent dissemination in patients without known metastasis has not been shown to be effective. 58 Nonspecific immunotherapy with bacillus Calmette-Guerin has not been shown to be effective in patients with extensive melanoma. 15, 58 Various other forms of immunotherapy are under investigation, including the use of interferons,68, 90 melanoma vaccines,15 monoclonal antibodies,89 and tumor-infiltrating lymphocytes. 123

SUMMARY Melanocytic nevi are common in children and adolescents, and the preponderance of these lesions are benign. Congenital melanocytic nevi, dysplastic nevi, and large numbers of common acquired nevi, however, may indicate an increased risk of malignant melanoma. With the exception, possibly, of giant congenital nevi, melanoma associated with these lesions generally occurs in adulthood. Nonetheless, some patients can be identified as being at increased risk for the development of melanoma during childhood. The poor prognosis associated with advanced melanoma and the curability of early lesions underscore the importance of prompt recognition of melanoma when it does occur in children. Furthermore, physicians who care for children are in a key position to decrease risk of melanoma throughout the lifespan by encouraging avoidance of excessive sun exposure during childhood.

REFERENCES 1. Ackerman AB: What nevus is dysplastic, a syndrome and the commonest precursor of malignant melanoma? A riddle and an answer. Histopathology 13:241-256, 1988 2. Albert LS, Rhodes AR, Sober AJ: Dysplastic melanocytic nevi and cutaneous melanoma: Markers of increased melanoma risk for affected persons and blood relatives, J Am Acad Dermatol 22:69-75, 1990 3. Alper JC: Congenital nevi: The controversy rages on. Arch DermatoI121:734-735, 1985 4. Alper J, Holmes LB, Mihm MC Jr: Birthmarks with serious medical significance:

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