The relative risk for melanoma arising within a congenital nevus is related to the size of the lesion. The timing of and clinical presentation of development of melanoma is also related to the size of the lesion. Medical decisions are individualized taking into account the perceived risk of malignancy, psychosocial impact, and anticipated treatment outcome. In this article, the common features of congenital nevi are discussed as well as the potential individual variations and their impact on treatment recommendations.
One of the most common skin lesions in a newborn infant is the congenital melanocytic nevus. These lesions pose considerable clinical dilemma given their frequency, wide variation in presentation, potential psychosocial impact, and potential for medical significance. All of these factors affect decisions regarding their treatment. In general, lesions are either observed or removed with excisional surgery. Occasionally intermediary procedures, such as biopsy or alternative surgical procedure, are considered. A congenital nevus on a child can be a source of anxiety and distress for parents. The medical significance of these newborn skin lesions is that over a lifetime they can be a marker for increased risk of malignancy, may be associated with rare syndromes, or can transform into melanoma. Thankfully, melanoma in children is rare. Nonetheless, it does occur and the risk for melanoma increases dramatically at puberty.
The relative risk for melanoma arising within a congenital nevus is related to the size of the lesion. The timing of and clinical presentation of development of melanoma is also related to the size of the lesion. Medical decisions are individualized taking into account the perceived risk of malignancy, psychosocial impact, and anticipated treatment outcome. In this chapter, the common features of congenital nevi are discussed as well as the potential individual variations and their impact on treatment recommendations.
Definition and classification
A congenital melanocytic nevus is composed of melanocytes, the pigment-forming cells in the skin. This is in contrast to the broader category of congenital “nevi,” which may include nevus sebaceous (sebaceous gland proliferation) and epidermal nevus (keratinocyte proliferation). In contrast to acquired melanocytic nevi, congenital melanocytic nevi are present on the skin at birth or within the first year of life. A tardive congenital nevus is one that is not present at birth but becomes clinically apparent within the first 2 to 3 years of life. Congenital melanocytic nevi are considered benign nevomelanocytic proliferations and are common, with estimates in prevalence at 1% to 6%.
At birth, the lesions may be lightly pigmented macules or patches that in some cases mimic café au lait macules. They may be pink at birth, as is more typical on the scalp, or multiple shades of brown black. They are commonly small and oval, but can be a range of sizes and unlimited potential shapes, with round, linear, curvilinear, geographic pattern and random shape among the most common forms. Multiple lesions can be found, coalescing on one anatomic area, discontinuous in a geographic area, or randomly scattered. Once fully developed, the typical appearance is that of a pigmented brown plaque that is round to oval in shape, with regular, smooth, and well-demarcated borders. In addition to variations in shape, the fully formed congenital melanocytic nevus can have variations in border and coloration such as ill-defined, fading borders that are shades of brown, areas of darker brown or black pigmentation either symmetrically in the center of the lesion or randomly distributed within the lesion. Variations can also occur in surface characteristics and nevi can have a pebbly or rough surface or extremely hyperkeratotic surface, and frequently exhibit hypertrichosis. Most congenial melanocytic nevi occur sporadically but familial clustering has been observed.
Treatment depends on the location, size, appearance, and symptoms of the lesion; parental concerns; and presence of other risk factors.
The most commonly used classification for congenital melanocytic nevi is based on size with small (<1.5 cm), medium (1.5–19 cm), and large (>20 cm) lesions defined by the largest dimension diameter anticipated in adulthood .
The term giant congenital nevus is used for nevi covering large segments of the body. Other classifications that have less commonly been used for congenital nevi include those based on relationship to an anatomic structure (palm-size multiples), ease of removal (requiring skin graft), and relative body surface area (BSA) of involvement (30% BSA significance).
In infants and children, classification according to size is based on eventual anticipated size, and thus lesions on the head greater than 9 cm or on the body greater than 6 cm in an infant are referred to as large congenital nevi because relative eventual growth to approximately1.5 times and 3.0 times the size occurs on the head or body, respectively.
Recently, a proposed refinement in classification recommends separating medium from large congenital melanocytic nevi (CMN) at 10 and 20 cm, respectively, and defining a giant CMN as one measuring more than 20 cm in greatest diameter.
In this classification, giant lesions are further recognized in 10-cm intervals (G1, G2, G3), and in patients with more than 50 satellite lesions, the size category is increased by one category to account for the increased risk of melanoma. This classification allows for more precise stratification according to size and therefore nevus burden. Since as a general principle with CMN, size correlates with the depth of the lesion into the subcutis and with the total number of melanocytes present in the lesion.
Clinical appearance has not been considered a classifying feature for congenital nevi but is important for assessment of malignant potential, with and without regard to size. Uniformity and symmetry of coloration, shape, border, and topography are important clinical distinctions and will be reviewed later. A homogeneous uniform color and symmetric shape CMN with uniform topography (eg, no distinct papules) ( Fig. 1 ) is less concerning than a multicolored CMN with an uneven surface and ( Fig. 2 ) with irregular borders.
Synonyms for CMN include garment nevus, bathing trunk nevus, giant hairy nevus, giant pigmented nevus, pigmented hairy nevus, nevus pigmentosus, nevus pigmentosus et pilosus, and Tierfell nevus. Nevus spilus, which is characterized by a café-au-lait–like macule or patch with speckled pigmented macules and papules within it, may represent a clinical variant of congenital melanocytic nevus, especially when papular areas are present within the lesion (nevus spilus papulosis).
Tardive congenital nevi are nevi with congenital features that are not present at birth but instead arise within the first 1 to 2 years of life.
The term congenital-nevus–like nevus refers to a pigmented nevus that was not reported to be present at birth or shortly thereafter; however, it has histologic features consistent with a congenital nevus. It is unknown whether these represent congenital nevi that were present but not externally visible until later or whether these are actually acquired nevi with congenital histologic features. The prevalence of congenital-nevus–like nevus is estimated at 2% to 6% of the population. The term early-onset nevus has also been used.
Pathogenesis
The cause of congenital nevi is not known. In normal human development in utero, melanocytes are derived from the neural crest as melanoblasts and migrate from a dorsal location in the embryo ventrally to the skin, the central nervous system (CNS), eye, and adrenal glands between weeks 5 and 24 of gestation. Defects in migration or maturation are hypothesized. The molecular and genetic changes and chromosomal aberrations in congenital nevi are beginning to be characterized.
Somatic mosaicism and clonality have been suggested given the repetitive patterns of occurrence along developmental skin lines and the observation of twin spots.
Pathogenesis
The cause of congenital nevi is not known. In normal human development in utero, melanocytes are derived from the neural crest as melanoblasts and migrate from a dorsal location in the embryo ventrally to the skin, the central nervous system (CNS), eye, and adrenal glands between weeks 5 and 24 of gestation. Defects in migration or maturation are hypothesized. The molecular and genetic changes and chromosomal aberrations in congenital nevi are beginning to be characterized.
Somatic mosaicism and clonality have been suggested given the repetitive patterns of occurrence along developmental skin lines and the observation of twin spots.
Clinical presentation
Congenital nevi may have many different appearances in coloration, topography, and border, but the shape and pattern are often repetitive.
The congenital nevus is usually a round to oval shape and may be oriented with the long axis along lines of skin development ( Fig. 3 ). The color is usually brown to dark brown or black plaque with a rugose or mamillated topography.
Coloration
In the first few years of life, the lesions can be flat and less heavily pigmented color, and the appearance can mimic that of a café au lait macule ( Fig. 4 ). Occasionally congenital nevi, especially those located on the scalp and face can be pink-red and rarely without color (nonpigmented) ( Fig. 5 ). Rarely lesions may become hypopigmented or even regress.
More than one color can be present in a congenital nevus and most frequently are shades of brown and dark brown or black. The coloration can be present in a speckled pattern with darker brown papules randomly scattered in a tan-colored macular background (nevus spilus papulosis or speckled congenital nevus), or irregularly, randomly distributed papules or nodules in larger lesions.
The border of the nevus can be a different hue from the central body of the nevus, resembling a fried egg if darker color centrally than at the periphery, or, if lighter centrally and darker on the border, can resemble an eclipse. When congenital nevi consist of a predominantly pink color, they can have overlying hyperkeratosis and mimic a plaque of eczema.
On occasion, congenital nevi are not present at birth because the melanocytes lack visible pigment. In these cases, the CMN becomes clinically apparent within the first 2 years of life and is referred to as a “tardive” congenital nevus. In the case of a melanocytic nevus mimicking the appearance of a café au lait macule with tan brown color and macular instead of plaque morphology, the lesion thickens usually over a period of years, and the distinction toward true nevus becomes more evident in this time.
Shape and Configuration
Nevoid shape is generally oval, but round, geographic, curvilinear, arcuate, ink blot, leaflike, and more angular shapes such as square, rectangular, or triangular shapes can be seen. When multiple lesions are present, they can be present in the same anatomic segment or area or be randomly distributed on the body. When localized to one segment of the body, multiple lesions can be discontinuous in a random pattern or coalescing into one of the previously mentioned shapes, occasionally background tan coloration encompasses the group of individual nevi. Borders can be well defined or ill defined, can be uniform and regular, or can be irregular—either uniformly irregular or randomly irregular.
Location
Congenital nevi can involve any location in the skin including the mouth, palms and soles, and nails ( Fig. 6 ). When located in the mouth and nails, the lesions are usually macular. When located on the scalp, the lesion commonly displays a central area of coloration that is a different shade or color than the rim. Benign features of these lesions are symmetry of shape and pigmentation and a lack of other significant irregularities.
Secondary Changes
Although the surface is typically rugose and elevated, congenital melanocytic nevi can be flat, especially in the first 1 to 2 years of life. Randomly distributed papules may occur within an otherwise flat lesion. Alternatively, the entire lesion can be significantly elevated off the skin surface, resembling a tumorlike growth. Congenital melanocytic nevi frequently develop hypertrichosis (symmetric) over the surface and frequently this hair is hyperpigmented as well. This can be especially dramatic in the scalp where congenital nevi can have hypertrichosis as well as hyperpigmentation of the scalp hair in the area. As previously mentioned, eczemalike appearance resulting from hyperkeratosis is common. Very thick hyperkeratosis resembling an epidermal nevus can also occur. Erosion and ulceration of the surface can be found. Heavily pigmented large congenital melanocytic nevi over a limb may be found in association with underdevelopment of the limb, resulting in limb asymmetry.
Within an individual CMN, multiple variations in any of the previously mentioned descriptive characteristics can coexist.
Multiplicity
One lesion is normally present, but multiple congenital nevi can be present in the same patient, numbering hundreds. “Satellite nevi” describes the presence of multiple small congenital nevi in association with a large congenital nevus ( Fig. 7 ).
Clinical course
Congenital nevi will often “fill in” in the first few years of life. A once ill-defined border may become more defined and color may darken. They tend to thicken over a period of years. On the contrary, however, lesions may lighten over time as well and some lesions may even regress, especially in patients with vitiligo. The lesions can develop hypertrichosis, which, when uniformly distributed, is considered a normal occurrence. Hyperkeratosis can develop over the lesion secondary to dryness or concomitant eczema. Lesions once homogeneous can become speckled and lesions once flat can become papular or proliferative nodules can develop ( Figs. 8 and 9 ). In the first few years of life some lesions can grow rapidly, but many are assumed to grow proportionately with the growth of the child. Erosions or proliferative nodules can occur within the first few weeks of life and although they should be considered a potential sign of malignancy, this can be a normal occurrence as well.
Diagnosis
Diagnosis of a congenital nevus is usually a clinical diagnosis made by history of the nevus since birth and the distinctive clinical appearance of that of a larger nevus that has a rugose topography (see Fig. 2 ). Diagnosis can be verified via skin biopsy, when necessary, which usually demonstrates typical histologic features.
Histology
CMNs display characteristic histology including infiltration into the reticular dermis (and occasionally in the subcutaneous tissue including muscle and nerves extending in the subfascial plane), infiltration in and around skin appendages including hair follicles and sweat glands, and infiltration of single cells or single file between collagen bundles.
In giant congenital nevi, nevus cells have been found infiltrating the blood vessels and lymphatics. Although the vast majority of congenital nevi share these features, some truly congenital nevi that are small may not display this histology. Many different histologic subtypes of congenital nevi exist with junctional, deep, blue, combined, and Spitz representing some of the more common descriptive subsets.
The misdiagnosis of pigmented lesions is common and they can often be difficult to distinguish from other entities. For this reason, histologic interpretation of congenital melanocytic nevi that are atypical or questionable should be made by a pathologist experienced in the interpretation of pigmented skin lesions.
Significance
A congenital nevus can have medical, cosmetic, and psychological implications. Congenital melanocytic nevi have been associated with the presence of other congenital skin lesions as well as random internal associations.
Presence of congenital nevi as part of the NAME (LAMB or Carney) syndrome has been described.
Malignancy has been reported in increased frequency within these lesions including melanoma and rhabdomyosarcoma, liposarcoma, and peripheral nerve sheath tumor. The most significant feature of a congenital nevus is the associated risk for transformation into malignant melanoma.
Although the exact risk of transformation is unknown, estimates for risk of transformation vary and the lifetime risk ranges from 4% to 10%. Smaller lesions are thought to have lower risk for transformation than larger congenital nevi relative to the “nevus burden.” The risk for small CMN is controversial and is thought to be between and 0% and 4.0%, and for those with large or giant CMN the risk estimates are between 4.5% and 10.0%.
Earlier estimates that were higher (as high as 42%) are now thought to be flawed from methodology or lack of improved histology. Although there are multiple reports of melanoma arising in small congenital nevi, studies fail to show an overall increased risk in this subset. Many of these small lesions are removed earlier in life before the onset for the greatest risk of melanoma; the impact of this on the natural history is unknown.
Melanoma arising from large congenital nevi presents in a different manner in large congenital nevi than in small congenital nevi. Melanoma typically presents at a very young age (first 2–5 years of life) in these larger lesions. Seventy percent of patients with a large CMN diagnosed with melanoma are diagnosed within the first 10 years of life.
Melanoma most commonly begins in deeper dermis or subcutaneous tissue in larger lesions and therefore often presents as a palpable nodule. Patients with melanoma in early childhood may be diagnosed with melanoma of unknown primary origin site because the focus of melanoma is hidden somewhere deep in the skin or subcutaneous tissue and cannot be found. Melanoma that is deep to the surface of the skin may be difficult to find in these larger lesions. Melanoma associated with these lesions may alternatively present outside of the involved skin and instead within the associated areas of neurocutaneous melanocytosis in the central nervous system.
Smaller lesions of congenital nevi are thinner in their depth of penetration into the skin and thus melanocytic aberrations occur in the superficial skin layers (at the dermal epidermal junction rather than in the subcutis). The transformation into melanoma is more commonly noticed as a change in pigmentation and/or shape of the lesion. The most frequent presentation is an area of hypopigmentation (or hyperpigmentation) on the periphery of the lesion. In these smaller congenital melanocytic nevi, the development of melanoma more often is not until adulthood, perhaps related to the smaller burden of nevus cells and therefore less cell cycle activity.
In addition to being precursors to melanoma, the presence of a CMN may be a risk factor for the eventual development of melanoma anywhere on the skin, not necessarily within the lesion. The presence of a congenital nevus has been associated with an increase in the development of melanoma over a lifetime. Some investigators think this is controversial.
Parental anxiety can also be significant in patients with congenital nevi. Anxiety is expected regarding potential development of skin cancer in pigmented lesions; however, beyond the risk of cancer, the presence of a congenital nevus can contribute to anxiety because of the social stigmatization from the visual presence of a lesion that is different or disfiguring, anxiety regarding changes within a lesion, requirements for increased sun precautions, knowledge of risk of associated conditions such as neurocutaneous melanocytosis, or pain or discomfort associated with multiple medical procedures or scars. Behavioral changes have been found in as many as 30% of children with a large CMN, which may result from or contribute to family stress.
Neurocutaneous melanocytosis
Neurocutaneous melanocytosis is a rare syndrome of increased melanocytes in the CNS in the presence of congenital nevus on the skin. The first historical classification in 1972 defined the condition as having (1) large or numerous pigmented nevi in association with leptomeningeal melanocytosis or melanoma, (2) no evidence of malignancy in any of the skin lesions, and (3) no evidence of melanoma in any location other than the meninges. The criteria have been refined more recently to the widely accepted definition of (1) the presence of a large CMN (>9 cm on the head or 6 cm on the body) or multiple (more than 3) congenital melanocytic nevi on the skin; (2) no evidence of cutaneous melanoma, except in people without meningeal melanoma as proven by biopsy; and (3) no evidence of meningeal melanoma, except in patients with benign cutaneous histology (also proven by histology). Whereas the presence of increased melanocytes in the CNS may indicate proliferation of benign melanocytes (neurocutaneous melanocytosis [NCM]) or malignant melanocytes (primary melanoma or metastatic melanoma [MM]), neurocutaneous melanocytosis refers to the presence of an increased number of melanocytes in the CNS or meninges without melanoma. Melanocytes are present normally in the CNS, but in the presence of NCM, they are increased in number and usually associated with the existence of a CMN. Although the exact incidence of NCM is unknown, this is a rare phenomenon.
NCM can be asymptomatic or symptomatic. Symptomatic NCM is associated with a grave prognosis, and thus it is important to screen all at-risk patients for symptoms of NCM. Proliferation of melanocytes in the CNS can result in a variety of complications depending on the location of the melanocytes, including obstruction of cerebrospinal fluid, compression of vital structures, and even death.
The risk for associated NCM in a patient with a congenital nevus is thought to be greater in patients with large lesions, which, as previously defined, includes those that are anticipated to be greater than 9 cm on the head or 6 cm on the body. In patients with large CMN, the subgroup of patients with a large CMN in an anatomic location that is posterior (eg, the posterior head, neck, spine, or paravertebral location) are the patients most likely to have associated NCM, and especially those with multiple satellite nevi.
It is important to recognize that even patients with multiple medium-sized congenital nevi are also at risk for NCM, as are those with multiple satellite (small) CMN (>3) without a large nevus.
Diagnosis of neurocutaneous melanocytosis is made by magnetic resonance imaging.
Increased melanin is detected most commonly in the cerebellum or anterior temporal lobes and manifests with thickening of the leptomeninges and/or T1 (less likely T2) shortening in the brain parenchyma or meninges. Findings can be subtle and difficult to interpret and experience in interpreting the radiologic findings in these lesions is necessary.
NCM usually presents in the first few years of life, with rare cases reported in the second or fourth decade. Although most patients with NCM are asymptomatic, symptoms may include seizures, hydrocephalus, developmental delay, motor delay, nerve damage or spinal cord compression, or impaired mental status. Symptomatic patients generally present earlier, within the first 2 years of life.
There is no standard recommended screening for NCM or follow-up interval. Patients planning complicated surgical resection of the CMN frequently undergo screening MRI. MRI before 4 months of age is more sensitive, because myelination of the CNS after that time can obscure subtle infiltrates. Approximately half of all patients with large CMN lesions were screened in a registry-based study.
The interval for re-screening of positive patients is determined by the individual circumstances, such as extent of involvement of the melanocytosis and presence of neurologic symptoms. The necessity for follow-up MRI evaluation a patient with an initial negative screen is unknown. Although early MRI follow-up has been recommended for those with diagnosis of NCM, close neurologic follow-up seems to be a reasonable alternative, as current treatments are not curative and are directed toward relieving symptoms.
Treatments for neurocutaneous melanocytosis include those to control seizures, and/or interventions to relieve intracranial pressure, such as shunt placement, and those to stop proliferation of melanocytes. Combined chemotherapy and radiation has also been attempted but not met with much success. Unfortunately, interferon alpha and interleukin (IL)-2 have also been ineffective in treating melanoma in the CNS. Other chemotherapy agents are under investigation for CNS disease. Surgical resection has also been performed, although even with treatment, the prognosis is not altered.
Regarding the projected outcome for NCM, there are 2 prognostic categories: those with asymptomatic NCM and those with symptomatic NCM. For the vast majority of patients who have symptomatic NCM, the outcome has been fatal within a few years after diagnosis. Treatment in these cases is palliative. For patients with asymptomatic NCM, there is a wider spectrum and the prognosis is unknown.
Melanoma associated with a large congenital nevus may also occur in areas of neurocutaneous melanocytosis.
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