III.8 Congenital Melanocytic Nevi

III.8 III.8.1 Introduction and Definition Congenital melanocytic nevi (CMN), reported in 1–6% of newborns [31], are defined as benign melanocytic nevi whose presence is determined in utero. This definition encompasses congeni- tal nevi that are visible at birth, as well as the

“tardive” congenital nevi, which become appar- ent shortly after birth [29, 44]. Nevi with con- genital features that lack history of being pres- ent since infancy are termed congenital nevus-like nevi.

Many different definitions have been pro- posed to distinguish small and large congenital nevi (CMN) [32]; however, the most widely ap- plied classification is based on the greatest diam- eter they are predicted to attain during adult-

Congenital Melanocytic Nevi

Alon Scope, Cristiane Benvenuto-Andrade, Ashfaq A. Marghoob III.8

Contents

III.8.1 Introduction and Definition . . . .106

III.8.2 Etiology and Pathogenesis . . . .106

III.8.3 Clinical Features . . . .107

III.8.3.1 Clinical Variants . . . .109

III.8.4 Dermoscopic Criteria and Other Diagnostic Modalities . . . 110

III.8.5 Relevant Clinical Differential Diagnosis . . . 111

III.8.6 Histopathology . . . 111

III.8.7 Management . . . 111

III.8.7.1 Clinical Follow-up . . . 114

III.8.8 Case Study . . . 114

References . . . 116

hood, described as small (<1.5 cm), medium (1.5–19.9 cm), and large (20 cm or more). Given that most CMN grow in proportion to the ana- tomic site after early infancy [42], a factor of 1.5 for head lesions and a factor of 3 for all other anatomic areas can be used to estimate their size in adulthood and classify lesions in children.

Small CMN are seen in 1:100 newborns, medium in 1:1000, large in 1:20,000, and giant, the sub- group of large CMN with a diameter of 50 cm or more, in 1:500,000. With increasing nevus size, the frequency of complications is higher. These complications include the development of ma- lignancies, namely melanoma and more rarely rhabdomyosarcoma, manifestations of neurocu- taneous melanocytosis and greater psycho-so- cial burden for the patient and parents.

III.8.2 Etiology and Pathogenesis The embryonic origin of melanocytes is the neural crest. As the neural tube is formed, the cells of the neural crest migrate and give rise to multiple progeny, including melanocytes and peripheral neural system cells. Cramer pro- posed the theory of the melanocytic differen- tiation pathway [12], summarized in Fig. III.8.1.

A corollary of this hypothesis is that develop-

mental anomaly at the neural crest stage may

give rise to the presence of excessive melano-

cytes in both the skin and leptomeninges, as

seen in neurocutaneous melanocytosis. Fur-

thermore, nevi in individuals with neurocuta-

neous melanocytosis and large CMN may con-

tain not only an absolute increase in the number

of melanocytes, but also more primitive cells

with increased proliferative capacity.

Congenital Melanocytic Nevi

Alon Scope, Cristiane Benvenuto-Andrade, Ashfaq A. Marghoob III.8

Several molecular pathways have been impli- cated in the pathogenesis of CMN and its associ- ated complications. Hepatocyte growth factor/

scatter factor (HGF/SF) is a multi-functional cy- tokine implicated in the control of melanocytic proliferation, migration, and differentiation.

Transgenic mice over-expressing HGF/SF devel- op excessive melanocytosis of the skin and lepto- meninges, clinically resembling neurocutaneous melanocytosis [46]. They also are prone to de- velop melanoma and rhabdomyosarcoma [47].

Another important pathway for the proliferation, migration and differentiation of melanocytes is the stem cell factor (SCF) – c-kit pathway. It was shown that in neural-crest cell cultures, c-kit-ex- pressing cells invariably give rise to melanocytic clones [28]. In CMN, intense c-kit staining was found in proliferative nodules [19], which are rapidly growing benign nodules that arise within CMN in the early neonatal period and often prompt concern of malignancy. The darker pig- mentation of proliferative nodules may be the result of stimulation of the Mitogen-activated protein kinase (MAPK) pathway, downstream of

c-kit, leading to increased tyrosinase activity [19]. In addition, proliferative nodules display frequent chromosomal aberrations that are dif- ferent from those found in MM. Losses of chro- mosome 7 are found in nodular proliferations, whereas frequent losses of chromosomes 9 and 10 tend to be characteristic of MM [2].

Dysregulated activation of N-RAS/BRAF/

MAPK signal transduction pathway has impor- tant implications in melanoma progression [43].

Activating mutations in N-RAS have been found in 28–56% of CMN studied [10, 38]. The prog- nostic significance of N-RAS mutations in CMN remains to be elucidated, but interestingly, N- RAS mutations were reported to be associated with as many as one-third of nodular melano- mas [23]. Mutations in BRAF were found in 46–

86% of CMN in some small series [40, 53], while not in others [5], suggesting that this mutation may be an acquired event. Nevertheless, despite constitutive oncogene up-regulation, develop- ment of melanoma in CMN probably requires loss of the cellular mechanisms of senescence, such as the p16-Rb pathway, as well as immor- talization by telomerase activation [6, 36].

It is postulated that large CMN, which con- tains immature melanocytes, can undergo spontaneous mutations resulting in melanoma, thus accounting for the tendency of melanomas to develop early in life in patients with large CMN. In contrast, smaller CMN, composed of mature, differentiated nevo-melanocytes, may require exogenous influences, such as ultravio- let radiation, to induce mutations; thus, if mela- noma is seen in association with small CMN, it usually occurs later in life, similar to melano- mas that are associated with acquired nevi.

III.8.3 Clinical Features

Typically, CMN are round or oval pigmented le- sions with sharply demarcated borders. Their surface may be smooth (Fig. III.8.2), cerebri- form, rugose, verrucous, or lobular. CMN often have a diffuse homogeneous brown color; how- ever, some may have a multi-shaded pigment pattern, varying from light to dark brown (Fig. III.8.3). Others may be speckled with “is- lands” of darker or lighter pigment. Hypertri-

Fig. III.8.1. Pathway of melanocytic migration and dif- ferentiation, based on Cramer’s melanocytic differentia- tion pathway theory [12]. Melanocytes migrate from the neural crest to the dermis through the sheaths of periph- eral nerves. Immature melanocytes in the dermis then migrate to the epidermis and follicular epithelium, differ- entiating into the mature dendritic melanocytes capable of supplying melanin to the neighboring keratinocytes (i.e., epidermal–melanin unit). Other melanocytes from the neural crest migrate to visceral sites, including the leptomeninges, retina and inner ear

III.8

chosis, appearing at birth or by late childhood, is common (Fig. III.8.2). Although CMN are usually asymptomatic, some lesions may be as- sociated with pruritus, xerosis, and anhydrosis.

Over time, they may develop a nodular surface and become darker or lighter. Less commonly they may lose pigmentation or, in rare cases, re- gress [13, 48]. Some patients develop leukoder- ma, which can result in a halo phenomenon, fading of the nevus, and vitiligo-like lesions in distant skin sites [22]. This depigmentation is usually not associated with malignant degener- ation.

Patients with large CMN are additionally at risk for neurocutaneous melanocytosis [8]. Me- lanocytes occur naturally in the central nervous system where they usually remain quiescent. In neurocutaneous melanocytosis, however, there is an error in embryonal neuro-ectodermal morphogenesis, with dysregulated growth and migration of melanoblasts. Melanocytes at the leptomeninges may undergo asymptomatic be- nign proliferation (asymptomatic neurocutane- ous melanocytosis) or elicit neurological signs and symptoms secondary to impaired cerebro- spinal fluid circulation, mass effect, or intracra- nial hemorrhages (symptomatic neurocutane- ous melanocytosis). Some of these cells may give rise to melanoma. The incidence of symptom- atic neurocutaneous melanocytosis among pa- tients with large CMN is reported to be between 4.5–11% [1]. Based on MRI screening, the inci- dence of asymptomatic findings in the central nervous system among patients with large CMN has a range between 4.8 and 30%, with notable variability in study design [1, 15, 16]. The rate of development of symptomatic neurocutaneous melanocytosis among patients with a positive MRI is reported to be approximately 7% over 5 years of follow-up [15]. Patients at greatest risk for developing neurocutaneous melanocytosis are those with large CMN on the posterior axis and/or the presence of more than 20 satellite nevi (Fig. III.8.4) [14, 33]. Symptomatic neuro- cutaneous melanocytosis carries a poor progno- sis, even in the absence of malignant prolifera- tion. Neurological signs of cranial hypertension, such as hydrocephaly and seizures, may arise.

Patients with large CMN presenting with subtle motor and behavioral or development problems must also be carefully evaluated for neurocuta- neous melanocytosis.

CMN can occasionally give rise to melanoma or, less frequently, other malignancies such as rhabdomyosarcoma, liposarcoma, and malig- nant peripheral nerve sheath tumor [20]. The risk of melanoma seems to correlate, to some degree, with the size of the nevus, with larger lesions carrying the higher risk. Overall, the lifetime risk for developing cutaneous or extra- cutaneous melanoma in patients with large CMN is between 4.5 and 10% [7, 50]. The risk of developing melanoma in small and medium

Fig. III.8.3. Melanoma detection in a large and hetero- geneous congenital nevus, as presented here, can be dif- ficult, demanding careful follow-up and consideration for prophylactic removal of specific areas as clinically indicated

Fig. III.8.2. Large congenital nevus with smooth surface and homogenous brown color as focal depicted here is relatively easy to follow-up clinically, as change in color or texture can be promptly detected. Hypertrichosis is common and carries no prognostic value

CMN is even less well known but is reported to be between 0 and 4.9% [41]. Unlike melanomas developing in large CMN, which occur before puberty, melanomas occurring in small and medium CMN generally develop at or after pu- berty. Also, melanomas developing in small or medium CMN often begin at the dermo-epider- mal junction and at the peripheral edge of the nevus; thus, they are more readily detectable than melanomas developing in large CMN, which frequently occur below the dermo-epi- dermal junction. Signs of malignant degenera- tion occurring within CMN include the sudden appearance of a nodule or a dark pigmented area, itching, pain, bleeding, and ulceration. It is noteworthy that biopsy specimens of prolifera- tive nodules that develop within large CMN, particularly those found during early infancy, may have histopathological features that resem-

ble melanoma and yet have a benign clinical be- havior [52]. Previous reports of melanoma risk as high as 42% may have been over-estimated due to this histopathological phenomenon. It is advised that excision biopsies of CMN be read by a dermato-pathologist experienced with pig- mented lesions.

III.8.3.1 Clinical Variants

Nevus spilus (speckled lentiginous nevus), seen in 0.2% of newborns, is characterized by a tan well-circumscribed patch that is speckled with darker macules or papules (Fig. III.8.5). Histo- pathologically, the background tan patch con- sists of lentiginous proliferation of single mela- nocytes with elongation of the rete ridges and epidermal hyperpigmentation, whereas the speckled component shows junctional melano- cytic nests and less frequently dermal nests. In addition, cases of nevus spilus in which the speckled component was histopathologically consistent with atypical [18], Spitz [9, 21], and

Fig. III.8.4. Patients with large congenital melanocytic nevi on the posterior axis in the presence of many satellite nevi, as depicted in this figure, are at risk for developing neurocutaneous melanosis

Fig. III.8.5. This 13-year-old girl was born with multiple large segmental speckled lentiginous nevi. This case il- lustrates the clinical overlap between speckled nevus and congenital melanocytic nevus

III.8

blue nevi [11, 24] have been described. There are several reports of melanoma arising in nevus spilus [39, 51], although an increased risk was not confirmed in a case-control study [26]; thus, a reasonable approach, especially for larger le- sions, would be careful follow-up, assisted by photography, and monitoring for clinical chang- es similarly to the approach for larger-sized CMN.

III.8.4 Dermoscopic Criteria and Other Diagnostic Modalities

The four most common global dermoscopic patterns seen in CMN are (a) reticular, which can consist of diffuse or patchy network; (b) globular, mostly composed of dense globules of variable sizes. If the globules are large and an- gulated, the term “cobblestone-like” is used (Fig. III.8.6); (c) reticulo-globular, mostly with central globules and peripheral network (Fig. III.8.7). Globules appearing in the holes of

Fig. III.8.7. This medium- sized congenital nevus shows a reticular globular dermoscopic patterns, with hypertrichosis, central bluish globules, and patchy pigment network

Fig. III.8.6. This small congenital nevus shows a globular dermoscopic pattern

the network are termed “target network with globules”; and (d) diffuse homogenous brown pigmentation (occasionally with remnants of network or globules). In large CMN there are often multiple “islands” of pigment; however, each island has an organized and homogeneous dermoscopic appearance.

Specific dermoscopic findings that are com- monly observed in CMN include hypertricho- sis, milia-like cysts, and peri-follicular hypo- or hyperpigmentation. Although milia-like cysts are considered the “classic” dermoscopic sign of seborrheic keratoses, they should not divert the correct diagnosis in the presence of clinical and dermoscopic structures suggestive of a congeni- tal nevus. A multi-component pattern can be seen occasionally, consisting of three or more dermoscopic structures, often distributed asym- metrically. Since melanomas are often multi- component as well, this pattern in CMN should be viewed and managed with caution. In small- to-medium CMN, melanoma usually arises at the dermo-epidermal junction, a level well visu- alized by dermoscopy, whereas in large/giant CMN, melanoma may originate too deep in the tissue to be appreciated with dermoscopy.

Another non-invasive in-vivo imaging tool, reflectance confocal microscopy (see Chap. II.1), was reported to be useful for diagnosis of CMN [34]; however, its current effective depth of im- aging only reaches the papillary dermis and the procedure is time-consuming; thus, its use may be limited to small-to-medium CMN, similar to dermoscopy.

III.8.5 Relevant Clinical Differential Diagnosis

Small CMN can resemble acquired nevi, mela- noma, and pigmented seborrheic keratosis. Me- dium-sized CMN, particularly ones that are flat, can resemble café-au-lait spot, Becker’s ne- vus, epidermal nevus, and melanoma. Large and giant CMN are usually readily diagnosed.

Nevus spilus should be distinguished from ag- minated nevus by the lack of the brown back- ground in the latter.

III.8.6 Histopathology

Histopathological findings that distinguish congenital from acquired nevi are: (a) nevus cells with a band-like arrangement in a thick- ened papillary dermis reaching the reticular dermis; (b) nevus cells around and/or within epithelial adnexal structures (including hair fol- licles, sweat and sebaceous glands) as well as around blood vessels and nerves; and (c) pres- ence of nevus cells between the dermal collagen fibers singly or in Indian files. There is direct correlation between the size of the nevus and the depth of nevus infiltration. Medium to large CMN often reach at least the subcutaneous fat, whereas more superficial involvement of the re- ticular dermis may be seen in small CMN [27].

Also, the dermis is diffusely involved in large CMN, but tends to have patchy nevus cell infil- tration in small CMN [27]. The nevus cells in the dermis show the maturation phenome- non – the superficial cells have greater tendency to form nests, whereas the deeper cells are indi- vidually dispersed.

III.8.7 Management

Management of CMN must be tailored for each patient and lesion. Beyond the melanoma and neurocutaneous melanocytosis risk, there are often psychosocial/developmental concerns which should be reviewed. All of the following aspects should be taken into account: location, size, depth and appearance of the nevus; the likelihood of improved cosmesis; the potential for decreasing melanoma risk; general risks in- volved with anesthesia and surgery; degree of residual scarring; anticipated functional im- pairment; and discomfort. Based on these fac- tors, some CMN may not be amenable to surgi- cal excision. To reach a balance between decreasing the risk for developing melanoma through prophylactic removal of as much of the nevus as possible and attaining acceptable cos- metic results is one of the main objectives in the management of CMN (Table III.8.1).

Surgical excision is the most commonly used

method for treating CMN; however, there is a

wide range of available treatment modalities,

III.8

from dermabrasion and curettage to chemical peel and laser ablation (Table III.8.2). The choice on the best treatment usually relies on the phy- sicians experience and patient’s expectations

[17, 49]. For those patients in whom lesion re- moval is considered, surgery should be planned taking into account the fact that the best surgi- cal scars result from surgery performed early in

Table III.8.1. Absolute and relative indications for treatment of congenital melanocytic nevi

Treatment indica-

tions Reasons

Absolute

Malignancy develops Complete excision of the malignant tumor. Even a small congenital nevus that develops suspicious changes, becomes symptomatic or is irregular warrants excision Metastatic melanoma

with unknown primary

When the primary cutaneous melanoma is not found, the clinician must consider the possibility that a melanoma may be “hidden” within a congenital nevus.

A positron emission tomography scan may help in locating the primary focus of melanoma

Relative Prophylaxis

of melanoma Prophylactic removal should be strongly considered for lesions that are thick, rugous, and heterogeneous, making it difficult to detect melanoma within the nevus. Lesions that present in covered areas of the body (scalp, medial buttocks, perianal, and genital) may be clinically difficult to follow. Note: For congenital nevi

<1.5 cm in diameter, the risk for developing melanoma is considered low enough not to justify prophylactic removal

Physician

and patient anxiety Anxiety regarding the risk of melanoma is a factor in the decision to remove a congenital melanocytic nevus of any size. Families should be aware that while melanoma, neurocutaneous melanocytosis, and other complications can develop, the majority of affected individuals will not develop complications and clinical follow-up is an acceptable management option

Cosmesis Up to 30% of patients with large congenital nevi have social and behavioral/

emotional problems [25]. Patients, families, and physicians alike are usually of the opinion that a scar, even if extensive, is more socially acceptable than a large nevus

Fig. III.8.8. Photographic follow-up of a patient with a heterogeneous congenital nevus of the posterior axis (left) subjected to staged excisions of the nevus starting

at the age of 9 months (center). Recurrence of pigment along the scar edge is common after surgery (right) espe- cially when lesions are excised before the age of 2 years

life. Additionally, the risk of melanoma in pa- tients with large CMN is reported to be higher in the first decade, whereas in smaller CMN the melanomas occur later in adulthood; thus, pro- phylactic surgery of large CMN should be per- formed as early as possible.

Another important aspect of the surgical treatment for CMN is that very large lesions

may require serial or staged excisions, with or without tissue expanders (Fig. III.8.8). It is often impossible to assure complete removal of all ne- vus cells, leaving open the possibility for mela- noma to develop post-surgically from remain- ing nevus cells, even decades after the initial surgical procedure [45]; thus, it is recommended that large CMN be removed down to the fascial

Table III.8.2. Congenital melanocytic nevi treatment options. MM melanoma

Treatment  

option Benefits Risks

Full-thickness

excision Reduces melanoma risk Excision of large nevi may leave cosmetically disfiguring scar

Cosmesis Often requires serial excisions, tissue expanders, or skin grafts

Requires general anesthesia Partial-thickness

excision Reduces melanoma risk Melanoma may develop from residual melanocytes Excision of large nevi may leave cosmetically disfiguring scar

Requires general anesthesia Less potential for scarring

than full-thickness excision Difficult to detect subcutaneous MM Curettage Potential reduction of

melanoma risk if done early Melanoma may develop from residual melanocytes Requires general anesthesia

Must be performed within first few weeks of life May produce good

cosmetic result Repigmentation of scarred skin

Scarring may make it difficult to detect development of MM

Dermabrasion Reduces melanoma risk Case reports of melanoma development after dermabrasion

May produce good

cosmetic result Post-dermabraded skin is thin, fragile, tender, and with reduced hair density

Reduced pigmentation may allow for easier detection of developing melanoma

Should be performed early in life.

Procedure becomes less efficacious with time

Laser Unknown to what extent it may or may not reduce melanoma risk

Melanoma may develop from residual melanocytes

Low potential for scarring Repigmentation

Improved recovery time Unknown mutagenic potential

III.8

layer [3]. While patients should be aware that of all treatment modalities presented in Ta- ble III.8.2, surgical excision is the only treat- ment that attempts to remove all nevus cells [4].

III.8.7.1 Clinical Follow-up

In the great majority of cases, CMN can be clin- ically followed annually by total-body skin ex- aminations, with or without baseline photogra- phy (Fig. III.8.9). Photographs of the nevus, satellite nevi, and/or scars may be of great ben- efit in assisting the physician with the detection of subtle changes that may indicate melanoma [37]. Dermoscopy is particularly useful to iden- tify small foci of melanoma within a CMN, di- rect physicians to specific biopsy sites, and pre- vent biopsy sampling errors that result in false-negative diagnosis of melanoma. Large CMN that are thick and rugous and where sur- gical excision is not feasible may benefit from periodic positron emission tomography scan surveillance [30]. Individuals with CMN and their families should be counseled about avoid- ing over-exposure to UV light [35].

Patients at higher risk for neurocutaneous melanocytosis should receive careful follow-up, and consideration for screening brain magnetic resonance imaging (MRI), ideally before the age of 4 months, when myelination obscures subtle melanin deposits in the brain. At this moment there is no effective treatment for leptomenin- geal melanocytosis or central nervous system melanoma.

Besides the medical follow-up all patients/

families should be offered the opportunity to contact support groups such as Nevus Outreach (www.nevus.org) or Nevus Network (www.ne-

vusnetwork.org). III.8.8 Case Study

At 7 days of age, the child shown in Fig. III.8.10 was referred to Memorial Sloan-Kettering Hos- pital for consultation for a large truncal CMN.

The nevus extended from the neck to below the mid-back and consisted of a brown patch stud- ded with dark brown-black macules and plaques, as well as a 4-mm dark nodule with a crusted erosion, which was compatible with a prolifera-

Fig. III.8.9. The resection of some congenital nevi may not be feasible. This nevus wraps around the entire cir- cumference of body. Surgical excision would result in substantial functional impairment. This patient is being followed periodically with total body skin examinations, palpation of the lesion, and dermoscopy and baseline photographs, in an attempt to detect subtle changes

tive nodule. In addition, eight satellite nevi were apparent, mostly on the trunk. Dermoscopy of this large CMN showed a diffuse globular pat- tern with foci of black dots. Given the size, mid- back location, and presence of satellites, the in- creased risk for developing melanoma and neurocutaneous melanocytosis were discussed with the parents, albeit emphasizing that most individuals with large CMN do not develop these complications. Moderate sun avoidance was advised. The foreseen changes in contour and color of the nevus as well as possible ap- pearance of additional satellite nevi were also discussed. The nevus was photographed, with close-up and dermoscopy images. As a multi- disciplinary approach is essential in such pa- tients, the child was referred to (a) pediatrician for growth and head circumference monitoring;

(b) a pediatric neurologist to monitor for neuro- logical abnormalities; (c) MRI of the brain and spine at baseline to assess for neurocutaneous melanocytosis; and (d) a plastic surgeon consul- tation to discuss possible surgical treatment op- tions. The family was referred to Nevus Out-

reach support group, a non-profit support organization for patients and families with large CMN. At 1 month of age, the nevus became focally more rugous, some of the speckled macules turned into papules, while the proliferative nod- ule had diminished in size, and there were over 30 visible satellites dispersed over the torso and extremities. The baseline MRI showed an equiv- ocal brain lesion suspicious for neurocutaneous melanocytosis, but there was no change at 6- month imaging, and clinically the patient re- mained asymptomatic. The parents decided to pursue surgery for cosmesis and possible reduc- tion of melanoma risk. A staged excision was undertaken, starting at 5 months of age for the portion with most heterogeneous appearance.

The staged surgeries continued over the next few years using tissue expanders. During 5 years of dermatological follow-up, the remaining por- tion of the nevus was noted to attain overall lighter color, albeit with focal appearance of darker papules as well as new satellites that are being monitored with digital photography.

Fig. III.8.10. At the age of 1 week, a 4-mm violaceous- brown proliferative nodule with a crusted erosion is seen on the background of a heterogeneously pigmented large

congenital nevus (left). At 1 year the nodule had dimin- ished in size, and the nevus has become more darkly pig- mented and hairy (right)

III.8 ^References

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Core Messages

■ Individuals with CMN can develop medical, cosmetic, and psychological problems.

■ The absolute risk for developing cutaneous melanoma in association with a CMN is low; however, the relative risk is greatest for patients with large CMN.

■ The risk of neurocutaneous melanocy- tosis and extracutaneous melanoma is greatest for individuals with a large CMN located on the posterior axis (para-vertebral) and in those with many satellite nevi.

■ Cutaneous melanomas arising in large CMN tend to develop early in life and often develop below the dermo- epidermal junction, making early diagnosis challenging. In smaller CMN, melanoma tends to develop in adult- hood and at the dermo-epidermal junction and thus early detection is more feasible.

■ Surveillance for malignancy entails inspection and palpation to help detect new subcutaneous nodules that may represent dermal melanoma.

■ Congenital nevi with a benign dermo- scopic pattern can be followed clini- cally, whereas nevi with a multi-com- ponent pattern or with an uncom- mon pattern should be viewed with caution.

■ Prophylactic surgery may reduce the risk of cutaneous melanoma; however, melanoma can still develop from residual nevus cells or in extracutane- ous sites.

■ Ideal timing for prophylactic surgery of large CMN is early in life. For smaller nevi, one may elect to wait until the patient can participate in the decision-making process.

■ Patients at high risk for neurocutane- ous melanocytosis should be evaluated by a pediatric neurologist and/or by MRI scanning (ideally before 4 months of age).

■ All patients should be instructed on

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