A working group of pediatric dermatology experts conducted a narrative review to describe care related to congenital melanocytic naevi (CNMs) in newborns and children. There are no published guidelines for most aspects of care, including routine skin care and visit intervals. There are few guidelines for surgical management; The most recent recommendations favor conservative practice.
Emerging evidence contributes to recommendations for screening MRI to evaluate neural melanosis and related central nervous system complications, however, more research is needed. The risk of melanoma is generally low, but those with large, giant, or multiple NMCs are at higher risk.
Multidisciplinary care, focused on family and patient preferences, is of utmost importance. Without standardized screening and management guidelines, questions abound regarding appropriate physical examination intervals, potential treatment including complete or partial excision, timing and frequency of imaging, melanoma risk, and evaluation for melanosis. neural.
This review highlights the current state of knowledge regarding the care of patients with NMC, reveals gaps in the skin care literature, and provides management recommendations. They also discuss cutaneous complications of NMC, such as pruritus, hypertrichosis, and wound healing.
Resources and referrals for families and providers can help patients navigate this sometimes challenging diagnosis. Finally, they contribute expert care recommendations to the current body of literature as a basis for the development of more comprehensive future care guidelines.
| Methods |
A working group of pediatric dermatology experts was convened at the Pediatric Dermatology Research Alliance to investigate best practices and recommendations for the care of CMN in neonates and infants. The Pediatric Dermatology Research Alliance is a union of pediatric dermatology research organizations across North America.
A comprehensive review of the literature was performed from January 1, 1998 to December 31, 2017, using as keywords "congenital" and “melanocytic” and “nevus” or “nevus” in PubMed, Cochrane Database of Systematic Reviews, PyschInfo, Ovid Medline, Embase and CINAHL.
A second search (which also included Web of Science) for articles published from January 1, 2018, to July 24, 2020, and a manual search of articles identified from reference lists and more recent publications complemented the query. initial. Among these searches, 2,594 reports were identified, with 1,144 eligible for inclusion after removing duplicates, reports in languages other than English, abstracts, and non-NMC articles. However, the level of evidence was low, with many reviews and case reports.
There were no randomized controlled trials. There were no reports addressing routine skin care for patients born with NMC, although several published surgical interventions, imaging, and melanoma risk.
The authors conducted a manual search for complementary articles and began a narrative review, including the most relevant, practical, robust, and impactful articles identified in this search as determined by the expert reviewers. They included recommendations for important aspects of care, denoting statements without published guidelines as “author recommendations” within the text. Although formal consensus methodology was not used, all authors had the opportunity to review and comment on these recommendations, and all authors approved them.
| Clinical presentation and pathophysiology of NMC |
Congenital melanocytic nevi (CNM) are collections of melanocytes in the skin, with variable extension to adipose tissue, muscles and around the adnexa.
They are typically present at birth, although some appear after several months and can be located anywhere on the skin. The reported incidence of CMN of any size varies widely from <1% to 31.7%1–8; most studies estimate an incidence of <1% to 3.6%.3–6.8
Estimates are limited by age at examination, with reports of newborns lacking NMC that become visible after birth, and studies of older children potentially including more nevi than are truly congenital based on recall bias. and appearance. Additionally, many studies focus on children in the United States, Europe, and Australia.1,3,4,7,8
The initial presentation varies from red to brown to black; They may initially be confused with vascular lesions before the brown color develops. CMN may be flat (macules and patches), palpable (papules, plaques, and nodules), or both.
They often have variations in pigment within a single lesion, or between lesions in patients with >1 CMN. Hypertrichosis may be present at birth or develop later. NMCs can change over time, and continuous monitoring is important. Generally, NMCs are not identified prenatally.9
NMC typically grow in proportion to a child’s somatic growth and are categorized by projected adult size.10 Small and medium-sized NMCs are more common than large and giant ones, which are associated with greater morbidity and an increased risk of associated melanoma. (see forecast).
Large or giant CMNs may occur along with smaller melanocytic naevi, which may be present at birth or develop over time. These smaller lesions were historically called "satellite" nevi; The term “satellite,” however, is neither developmentally nor spatially precise, and many authors prefer the term “multiple NMCs,” 11 with the total number of NMCs being important in categorization.10
Furthermore, multiple medium-sized NMCs without a large or giant NMC is a distinctive presentation. Krengel et al10 proposed characteristics to categorize CMNs including projected adult size, number of “satellite” nevi, site, color heterogeneity, and surface characteristics such as hypertrichosis or roughness. This scheme can be useful in clinical and research settings.
> Genetics
NMCs are caused by postzygotic somatic mutations and are not generally considered inherited. NRAS variants are the most common variants identified in large and giant NMCs, but BRAF , KRAS , APC , and MET variants , as well as rare protein fusions, are also reported.12 Other investigations of genotype-phenotype correlations are ongoing.13
> Neurocutaneous melanoma and melanosis
The lifetime risk of developing melanoma in association with a NMC is low.14–16 This risk varies depending on the size of the nevus. The incidence is reported between 0.7% to 2.2% for all lesions except for those with a giant CMN, in which the estimates are higher (3% to 8%).14–16
Neural melanosis , characterized by deposits of melanocytic cells along the leptomeninges or cerebral cortex or within the brain parenchyma, may be associated with NMC.
Neurocutaneous melanosis ( NCM) refers to the co-occurrence of neural melanosis and cutaneous nevi. Estimates of the overall incidence of NCM vary because different criteria are used in studies and case series examining imaging findings, and low-risk children are not routinely imaged.
In children considered high risk, the incidence of neural melanosis ranges from 17% to 41%. 17-19 The presence of neural melanosis is a risk factor for melanoma; In one study, patients who underwent MRI and were found to have neural melanosis had a 12% incidence of melanoma, compared with 2% of those without NCM.14
Notably, the population examined with MRI in this study only included patients with multiple CMNs, many of whom were seen in association with a large or giant CMN. In a small cohort of patients with multiple NMCs with giant NMC greater than 60 cm projected adult size or multiple NMCs without a major NMC, the incidence of melanoma was 8% (7/88).
The majority of these melanoma cases occurred in the CNS.14
Among fatal cases of pediatric cutaneous melanoma in a separate, large, multisite cohort study, 5 of 6 patients with melanoma associated with NMC had large or giant NMCs.20
Melanoma and neural melanosis are both more likely in patients with NMC who have a projected adult size >40 cm in diameter, numerous “satellite” naevi (many NMCs), and location on the trunk (which may be an indicator of the size of lesion) as well as patients with multiple medium-sized NMCs.17,21,22 Patients with multiple NMCs are considered at higher risk for NCM.
Historically, >20 NMCs was considered a strong risk factor.18,22 A recent proposal recommends imaging all patients with >1 NMC; however, this practice has not been accepted by all experts.19 An MRI of the brain and spine is the preferred screening modality.
Patients with neural melanosis can be symptomatic or asymptomatic. Symptoms may include seizures, headaches, rapid enlargement of the head circumference due to hydrocephalus, symptoms of spinal cord compression, and subsequent developmental delay.
| Management of the NMC |
> General skin care
There are no evidence-based standards or published guidelines on skin care in the infant with CMN. The recommendations here were extrapolated from general neonatal skin care and expert consensus.
> Bathrooms
Although studies on the barrier function of the skin overlying large and giant NMCs are lacking, scattered reports and clinical observations of xerosis, pruritus, and skin fragility support the concept of a skin barrier impairment in lesional skin. Bathing recommendations, therefore, include bathing with plain water or a soap-free cleanser at least 2 to 3 times a week followed by application of a mild emollient (authors’ recommendation).23 This may help improve skin hydration and skin barrier function.24
Soap-free cleaners are typically liquids with a neutral or slightly acidic pH. Mild emollients are creams or ointments with minimal or no fragrances or preservatives. The addition of an emollient after bathing results in less transepidermal water loss without an adverse effect on skin pH.25
> Xerosis and pruritus
Pruritus , especially in larger CMN, is common.26 Pruritus can occur with or without eczematous changes and fortunately rarely indicates malignant transformation.26 Eczematous changes may appear within or around the naevus (Meyerson’s phenomenon). 26 Thick emollients (creams or ointments with minimal or no fragrance or preservatives) are recommended for chronic treatment and low- to medium-potency topical corticosteroids twice daily as needed are added for acute eczematous eruptions (authors’ recommendation ).
> Skin fragility and wound healing
The NMC may show increased fragility resulting in ulcerations, erosions, and bleeding with minimal trauma.27
The neonate, however, should be handled the same as one would handle an unaffected newborn to foster parental bonding and minimize parental anxiety.
If ulcerations or erosions occur, the wounds should be gently cleaned with soap or a non-soap cleanser and water and Vaseline or a soft ointment and a bandage should be applied (authors’ recommendation).
Hydrocolloid or foam dressings, which are adherent but easily removable and gentle on the skin, are often helpful (authors’ recommendation). Topical or oral antibiotics are only indicated if an infection occurs.
Ulcers that do not heal should be evaluated for infection with cultures; Additionally, malignancy should be considered when evaluating chronic, nonhealing wounds, and biopsies should be performed as appropriate.27
> Hypohidrosis and anhidrosis
Anecdotal reports mention a lack of sweat glands histologically in some NMCs and some patients note hypohidrosis. Although more research is needed to explore this phenomenon, parents can be advised to avoid overheating and use cooling techniques, if appropriate.
> Photoprotection
There are no studies that specifically examine the effect of ultraviolet radiation on NMCs. Children with NMCs should follow the American Academy of Pediatric UV Radiation Protection recommendations.28 Photoprotective clothing (e.g., rash guards and hats) is particularly efficient at blocking the sun.
| Specialized care and comorbidities |
In the neonatal period, patients with large, giant, or multiple CMN of any size should pursue care with a pediatric dermatologist or general dermatologist with experience in CMN.
Unless there are clinical concerns (variation in color, nodules, symptoms, and/or location), referral to a primary care physician may be delayed in small and medium-sized solitary CMNs (authors’ recommendation).
> Visits to dermatology
During the initial dermatology visit, a complete skin examination, education and counseling, discussion of management, and recommendations for possible referrals and follow-up care are performed.
Evaluation of NMC involves (1) visual inspection, which may be assisted by dermoscopic evaluation, and (2) palpation. Palpation is particularly important because melanoma in NMC may present as deep nodules without overlapping color change within the dermis or subcutis, rather than within the epidermis.14 Serial photographs may be useful in monitoring the appearance of the nevus. and changes over time.
Palpation of regional lymph nodes is an important component of the physical examination in CMN patients at high risk for melanoma; however, both NMC and melanoma can proliferate in lymph nodes, and palpation cannot distinguish between benign and malignant proliferation.29,30 Clinical context, imaging, and biopsy, when necessary, inform this determination (recommendation of authors).
There are no evidence-based guidelines specifying visit intervals for NMC of any size. The frequency of dermatological visits is determined by the location and characteristics of the nevus, the age of the patient, the concerns and needs of the parents, and medical comorbidities (authors’ recommendation).
Benign-appearing, asymptomatic, small or medium-sized NMCs (low risk of malignant transformation) can often be followed by a primary care provider in well-child controls, while small or medium-sized changing or symptomatic NMCs or those with a unusual (e.g., variegated color) usually warrant referral to dermatology.
Larger, multiple, and changing naevi are generally managed closely by a dermatologist during childhood or at times when changes in the naevus are expected, such as puberty, due to the increased risk of melanoma and the need for family counseling. ; Visits every 3 months may be appropriate (authors’ recommendation).
After the first year of life, in the absence of particular concerns, the frequency of visits gradually decreases, but a minimum of an annual evaluation by a dermatologist is generally appropriate for large, giant, multiple CMNs or smaller CMNs with concern regarding their characteristics (authors’ recommendation).
Patients with concurrent medical conditions or undergoing immunosuppression may require special consideration due to a possible increased risk of melanoma.31,32 Additional factors may play a role, such as proximity of the patient and access to their dermatologist.
> Changes and growth within the NMC
Curiously, some nevi regress spontaneously.
Scalp NMCs in particular have a tendency to clear over time, although the histological presence of nevus cells has been reported to continue and therefore continuous skin examinations cannot be discontinued.33,34
The pigmentation of any NMC may evolve to include more mottling or speckled pigment, homogeneous or heterogeneous darkening or lightening, and/or a change in texture.35
The context of a patient’s skin pigmentation may be the most predictive characteristic in determining the ultimate color of the nevus.35 Changes in the surface over time include becoming more elevated, hypertrichotic, verrucous, cerebriform, mamillated, or papillated.
Between visits, parents, guardians, caregivers and/or patients should monitor nevi visually and with palpation and are encouraged to notify their doctor of any concerning changes, such as rapid growth, bleeding, pain, development of a lump or nodule. , or ulceration. These changes within a NMC should be evaluated promptly, preferably by a dermatologist (authors’ recommendation).
Importantly, melanoma can occur in the skin or in the CNS, and some children with large or giant CMN have had metastatic melanoma with no known primary site.14,16,36
Proliferative nodules, which are secondary benign melanocytic growths that can arise over time within a larger NMC, have clinical and histologic features overlapping with those of melanoma, but lack the genetic instability seen in malignancy. They can occur in early childhood or later and are diagnosed clinically or by pathology.37,38
Clinically, proliferative nodules may appear as papules, plaques, or nodules, with or without ulceration. Because there may be clinical and histologic uncertainty between proliferative nodules and melanoma, the decision to biopsy a new growth in an NMC is generally based on the physician’s level of concern for malignancy.
The size, location, appearance, and feel on palpation (eg, firm versus soft) can help determine whether a biopsy is necessary and the type of biopsy performed.
Histopathological examination of worrisome change or a possible proliferative nodule within a NMC should be performed by a dermatopathologist with experience in pigmented lesions in children because interpretation is often extremely complex.
Genetic studies, such as fluorescence in situ hybridization and comparative genomic hybridization, may be complementary diagnostic tools in more ambiguous lesions. Results from ancillary genomic testing may also drive treatment decisions for melanoma now that targeted treatments are available.
> Neural melanosis detection and monitoring
MRI of the brain and whole spine is used to detect and/or monitor CMN (screening, symptom-driven, and follow-up protocols differ).
Solitary, small, medium and large CMNs are low risk for CMN and MRI screening is not recommended unless signs or symptoms are found during the examination (authors’ recommendation).
Patients with multiple medium-sized NMCs, ≥10 "satellite" lesions, and giant NMCs are at high risk for NMC and should undergo MRI (authors’ recommendation).
Early MRI screening, without contrast, can often be performed using a "feed and swaddle" technique in newborns and even those younger than 2-3 months of age (although some will try this method up to the age of 6 months). to avoid the need for general anesthesia.39
In this age group, neural melanosis is not obscured by myelination and can be visualized without contrast.17 This may provide useful information in diagnosing the presence (or absence) of neural melanosis without the need for general anesthesia (authors’ recommendation ).
Telemedicine may be useful for primary care providers without close access to dermatologists to decide whether early MRI screening is warranted. Although it depends on the institution, some attempt noncontrast screening without anesthesia in older infants and children; However, such images may be somewhat less definitive due to rapid changes in brain myelination, again emphasizing that early images done without contrast are optimal.17,18,21 Additionally, motion artifact must be considered when imaging. determines the need for anesthesia.
Rapid-sequence (“fast-brain” or “one-bang”) MRIs have low resolution.40 There are no published data to validate rapid-sequence MRI in the investigation of neural melanosis, and this method is not currently recommended for screening. or symptom-directed imagery.
Among patients with ≥2 NMCs who underwent screening MRI, 79% showed normal findings.19 Intraparenchymal melanosis, the most common abnormality, was seen in 10%. 19 As a note, an MRI may also reveal additional findings in patients with CMN, such as cysts, tumors, malformations, hydrocephalus, and tethered spinal cord.19,41
An abnormal MRI in patients with CMN is the best predictor of clinical outcomes.
Although the vast majority of people with neural melanosis do well, its presence, particularly if extensive, means an overall increased risk of melanoma. Additionally, early imaging establishes a baseline in case complications or symptoms arise later.19 Additionally, imaging should be followed up or repeated for new abnormal neurological findings or developmental deficits.
As a note, symptom-directed imaging or monitoring of known lesions is not “screening” and therefore different guidelines for imaging protocols are recommended. An MRI in these cases typically requires contrast and sedation in young children. All images should be reviewed by an expert neuroradiologist familiar with MNC.
Patients with proven CMN should be referred to a pediatric neurologist. Neurodevelopmental evaluations, including neuropsychological testing, should be recommended. Patients with a speech delay or newborns with a failed hearing screening should undergo audiologic evaluation.
Some doctors recommend ophthalmology consultation, particularly in children with neural melanosis, because melanocytic lesions can be identified in the retina; however, this is controversial. In infants with structural abnormalities (eg, hydrocephalus or concern for a tethered spinal cord), neurosurgical consultation may be appropriate.
> Endocrine comorbidities
A small number of patients with NMC have been described as having distinctive facial features and CNS or endocrinologic abnormalities, which are collectively termed NMC syndrome.42 Premature thelarche, undescended testes, insulin insensitivity, and tolerance testing altered oral glucose levels warrant further investigation.43
> Psychological considerations
Referral to psychology may be considered in all affected children to address issues regarding quality of life and emotional and behavioral health.44 The impacts of NMC on the child’s social relationships and affective functions are not always predictable.
In a study with parental representation on health-related quality of life and psychological adaptation, parents of children with neurological sequelae, skin symptoms, and high levels of perceived stigmatization observed greater deficiencies in these domains.44
In a study involving adolescent self-report, 46% of adolescents responded “no” to a “small” impact on their skin-related quality of life, while 54% reported a “moderate” to “extremely” impact. big.”45
More research is needed on the relationship of the response with the patient’s age (experience over time) and size and location of the CMN. It is important to support families and children emotionally and with community resources. Many families find support from patient groups.
| Management of CMN: Surgery and Procedures |
The decision for interventions or removal of an NMC is complicated by numerous factors, including family preference, the size and location of the nevus, the patient’s age, general health, and prognosis if NCM or melanoma is present.
Importantly, prophylactic removal does not eliminate the risk of melanoma from residual nevus cells that may remain after removal and, especially for larger nevi, it may be nearly impossible to surgically remove an NMC completely.36 Additionally, the risk of CNS melanoma is not affected by prophylactic removal of the nevus.
Removal may be associated with several risks, such as multiple procedures, repeated general anesthesia, anxiety associated with treatments, postoperative pain, and scar appearance.
Potential complications must be weighed against potential improvement in the patient’s appearance, improvement in function if there is associated impairment, and psychosocial benefit (or lack thereof).
Shared decision making can help patients and their families make decisions about treatments by focusing the discussion on patient and family preferences and medical evidence.
> Surgery: small and medium NMC
In general, small and medium-sized lesions can be seen if there are no complications.46 Indications for surgery may include functional considerations, symptoms, difficulty managing an injury clinically, or stigma. The psychosocial impact of NMC can be variable and must be considered when making surgical decisions.45
> Surgery: large and giant NMC
Surgical approaches to large and giant NMC include serial excision, tissue expansion, local flaps, and grafting with skin or artificial skin substrates.
The benefits of serial excision include a single linear scar when size allows and no donor sites or large flaps.
Tissue expansion may allow a reduction in the number of surgical procedures and reduced time to complete excision of a nevus; Tissue expansion, however, has a high overall complication rate (18.2%), with 60% of these cases undergoing successful subsequent reconstruction.47
In particular, routine excision of large and giant NMCs has fallen out of favor, as the surgery presents its own risks and has not demonstrated a reduced lifetime risk of melanoma.46,48 Furthermore, neither NMC nor the risk of melanoma of the CNS is affected by surgical approaches.14 Additionally, disfigurement caused by resection and procedures has psychological effects and functional consequences, and must be considered along with the psychosocial impact of NMC on the child and family. Conservative management is now frequently recommended for large and giant CMNs, except when there are concerning findings on examination.46
> Other approaches to treatment procedures for NMC
Pigment-specific ablative lasers, curettage and dermabrasion have also been used to treat NMC. These non-excisional approaches are used primarily for cosmetic purposes, when surgical excision and reconstruction are not options.
Some authors suggest that these interventions may make melanoma more difficult to detect due to the resulting fibrosis and scarring.49
Risks of destructive treatment include scarring, depigmentation, need for repeated treatments, poor wound healing, infections and eventual repigmentation, which is common.
Some report worsening appearance after intervention, including disfiguring scars, keloids, and recurrent nevi.46,50 Many CMNs clear up over time without intervention, which should be considered before any cosmetic intervention.33,35
> Hair removal
Hair removal is poorly studied in children with CMN. Shaving, waxing, threading, chemical hair removal, electrolysis or trimming are low risk.
Hypertrichosis often becomes more prominent over time. For babies, simple hair trimming is generally adequate if caregivers wish to do so.
Laser hair reduction51 and electrolysis are more permanent and require serial treatment. Histological and dermoscopic changes in nevi have been noted after laser hair removal,52,53 but the risk of melanoma from these procedures is thought to be low.
| NMC Management: Medical Care |
Medical interventions for NMC are emerging and currently under investigation. They are based on the evolutionary understanding of NMC genomics and the target pathways involved in its growth and proliferation.
Current approaches are experimental and have been used infrequently for neonates and infants, except in rare cases of compassionate use. Research in this area may validate a role for medical treatment of infants with thick, itchy, or painful CMN that interferes with development.54–56
| Patient and family support |
Families may have little familiarity with NMC before their child is born and require immediate support and provision of reliable information about NMC and skin care. Provide information about patient advocacy and support organizations, find a care provider, sun protection, and melanoma.
| Conclusions |
CMNs vary in size, color, location, and associated comorbidities. Classification is based on size, number of lesions, and associated findings at birth, which helps predict prognosis and complications.
Management of large, giant, and multiple CMNs is complex and typically involves multidisciplinary care.
Optimal routine skin care recommendations have not been developed specifically for NMC care; Best practices are extrapolated from general child care. Screening guidelines are needed to standardize care and optimize outcomes.
| Comment |
This review on the management of CMNs provides a baseline guide for the pediatrician having compiled the available information.
The need for basal skin care, follow-up by the primary care physician and the specialist to screen for complications, and advice regarding studies and management are highlighted.
Evidence suggests the use of MRI for the detection of NCM and CNS complications, although more evidence will be needed.
The risk of melanoma is generally low, with large, giant or multiple CMNs being the highest risk.
The type of treatment to be performed should be evaluated according to the patient’s clinical picture and quality of life, patient and family preferences, and the risks of short- and long-term complications.
