Congenital Nevi 

Updated: Apr 24, 2019
Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD 

Overview

Background

Congenital nevi are present at birth and result from a proliferation of benign melanocytes in the dermis, epidermis, or both (see the image below). Occasionally, nevi that are not present at birth but are histologically identical to congenital nevi may develop during the first 2 years of life. This is referred to as congenital nevus tardive.[1]

The photomicrograph shows a symmetrical broad prol The photomicrograph shows a symmetrical broad proliferation of melanocytes in the papillary and reticular dermis with maturation with progressive descent; splaying between collagen bundles; and permeation of muscles of hair erection, blood vessels, and adnexa (hematoxylin and eosin stain, 20X magnification).

See Mole or Melanoma? Test Yourself With These Suspicious Lesions, a Critical Images slideshow, to help identify various skin lesions.

Congenital melanocytic nevi are one of several known risk factors for the eventual development of melanoma. Fortunately, melanoma remains an uncommon malignancy in prepubertal children, with an annual incidence of 0.7 cases per million children aged 0-9 years. Patient concerns regarding changing or worrisome-looking nevi are, nonetheless, very common. Moreover, by the time a child reaches adolescence, the incidence of melanoma increases substantially, with a rate of 13.2 cases per million children aged 15-19 years.[2] These melanoma metastasize and are thus life-threatening.[3]

While many sources have noted the so-called melanoma epidemic in adults, only in recent years have data documented an alarming increase in melanoma in adolescents. This increase, combined with the recognition of clearly identifiable melanoma risk factors in childhood, allows physicians of the 21st century to play a crucial role in the identification of children at risk for melanoma and to aid in the prevention of melanoma through education regarding the risks of ultraviolet light exposure.

Congenital melanocytic nevus can be divided into two types, the first being the most common, usually a solitary plaque growing in proportion to that of the child, and a second type composed of many lesions, at least one being large and surrounded by many others and sometimes involving bone and central nervous system.[4]

Pathophysiology

The etiology of congenital melanocytic nevi remains unclear. The melanocytes of the skin originate in the neuroectoderm, although the specific cell type from which they derive remains unknown.[5, 6, 7] One hypothesis is that pluripotential nerve sheath precursor cells migrate from the neural crest to the skin along paraspinal ganglia and peripheral nerve sheaths and differentiate into melanocytes upon reaching the skin.[8] One possible explanation for the presence of congenital melanocytic nevi is that an external insult results in a mutation that affects the morphogenesis of the embryonic neuroectoderm and migration of precursor cells to the skin. Multiple congenital melanocytic nevi may reflect a mosaic RASopathy, reflecting postzygotic activating mutations in NRAS.[9]

One study found that the MC1R (melanocortin-1-receptor) genotype, which corresponds to a red-haired genotype and a tendency to increased birthweight, was overrepresented in a cohort of congenital melanocytic nevi affected Northern European patients. How MC1R variants promote growth of congenital melanocytic nevi and the fetus itself is unknown as is the application of this finding to non-European and more darkly pigmented races.[10]

Congenital nevi have been stratified into 3 groups according to size. Small nevi are less than 1.5 cm in greatest diameter, medium nevi are 1.5-19.9 cm in greatest diameter, and large or giant nevi are greater than 20 cm in greatest diameter. Giant nevi are often surrounded by several smaller satellite nevi. An alternate definition is that a small congenital nevus is one for which primary closure is possible after excision.

Congenital nevi may also be seen as a component of neurocutaneous melanosis, a rare congenital syndrome characterized by the presence of congenital melanocytic nevi and melanotic neoplasms of the central nervous system. Rokitansky first described neurocutaneous melanosis in 1861.[11] The current diagnostic criteria for neurocutaneous melanosis are (1) large (>20 cm) or multiple (>3) congenital nevi in association with meningeal melanosis or melanoma, (2) no evidence of meningeal melanoma except in patients in whom cutaneous lesions are histologically benign, and (3) no evidence of cutaneous melanoma except in patients in whom meningeal lesions are histologically benign.[12]

Neurocutaneous melanosis may result from an error in the morphogenesis of the neuroectoderm, which gives rise to the melanotic cells of both the skin and meninges. Clinically, patients may present with increased intracranial pressure due to hydrocephalus or a mass lesion. The prognosis of patients with symptomatic neurocutaneous melanosis is very poor, even in the absence of malignancy. In one review of 39 reported cases of symptomatic neurocutaneous melanosis, death occurred in more than half the patients within 3 years of the onset of neurological symptoms, and most deaths were in patients younger than 10 years.[12]

Mutations in NRAS in congenital melanocytic nevi can cause mitogen-activated protein kinase activation and may represent early events in melanoma development.[13]

Oncogenic missense mutations in codon 61 of NRAS were found in affected neurological and cutaneous tissues in 12 of 15 patients with congenital melanocytic nevi with neurocutaneous melanosis, implying single postzygotic NRAS mutations were responsible.[14]  However, the higher risk of a large or giant congenital melanocytic nevus becoming malignant compared with common acquired nevi is not explained by the presence of mutations in MAPK pathway genes.[15]

Etiology

The etiology of congenital melanocytic nevi has not been elucidated. One possible cause is a mutation due to an external insult.[16] An association between infantile hemangiomas and congenital melanocytic nevi has been suggested.[17] Future investigation may yield more definitive causative factors.

Epidemiology

Frequency

Congenital nevi are present in 1-2% of newborn infants. One small study in Spain found a higher prevalence of congenital melanocytic nevi in preterm infants, females, and nonwhite infants, whereas maternal age, number of previous pregnancies, and birth weight did not appear to influence the prevalence.[18]

Race

No racial predilection is recognized for congenital nevi.

Sex

Congenital nevi occur in both sexes, with no known predilection.

Age

To be considered congenital nevi, lesions must be present at birth.

Prognosis

The prognosis for patients with small or medium-sized congenital melanocytic nevi is good. Although the risk of developing melanoma in these lesions has not been quantified, it is generally regarded as only slightly higher than that of normal skin. Despite the increased risk for melanoma in patients with giant congenital melanocytic nevi, the vast majority of patients never develop melanoma. Therefore, prognosis remains good in these patients, especially if the lesions are examined regularly for signs of atypia.

Prognosis in cases of symptomatic neurocutaneous melanosis is quite poor.

Mortality/morbidity

Congenital nevi, depending on size and location, may have a significant impact on cosmesis. Giant congenital nevi place individuals at an increased risk for the development of melanoma at the site of the nevus. For giant congenital melanocytic nevi, the risk of developing melanoma has been reported to be as high as 5-7% by age 60 years.[19, 20] One study suggests that the risk of melanoma may be greater in those with giant congenital melanocytic nevi with more satellite lesions or a larger diameter,[21] although it is unlikely to be so high.[22] Another suggests multiple satellite nevi alone or with associated posterior midline location of large congenital melanocytic nevi is linked with increased risk.[23] Additionally, melanoma developing within giant congenital nevi may develop during childhood and occur deeper in the tissue where it is harder to detect clinically.

While the general consensus regarding smaller nevi is that they pose a greater risk for the development of melanoma than normal skin, this risk has not been quantified. Also suggested is that melanoma developing within smaller congenital nevi usually occurs at puberty or later and develops more superficially in the skin, where it is easier to detect clinically.

Patient Education

All people need to be educated on the importance of protection from ultraviolet light exposure. This is especially important in people who have congenital melanocytic nevi, particularly the giant type, because they are already at an increased risk for the development of melanoma.

For patient education resources, see the Skin, Hair, and Nails Center, as well as Skin Cancer and Mole Removal.

 

Presentation

History

The presence of congenital nevi may be reported by adults, adolescents, or the parents of infants and children.

Physical Examination

Nevi may be located anywhere on the body. Classification as a congenital nevus depends in large part on an accurate history or photographs or medical reports from birth.

Scalp nevi in children younger than 18 years old tend to have perifollicular hypopigmentation that creates the appearance of scalloped, irregular borders if occurring on the periphery, or variegation in pigmentation, if occurring within the nevi.[24]

Congenital melanocytic nevi affecting acral volar skin in children are larger, more asymmetrical, and commalike compared with their acquired counterpart.[25]

Complications

Patients with giant congenital melanocytic nevi have an increased risk of developing melanoma (as high as 5-7% by age 60 y). The lifetime risk of malignant transformation associated with smaller nevi is surely smaller than that for giant nevi but is unknown at this time.

Large congenital melanocytic nevi are associated with an increased risk for developing cutaneous melanoma, leptomeningeal melanoma, neurocutaneous melanocytosis, malformations of the brain, and, rarely, rhabdomyosarcoma and liposarcoma. The risk of developing malignancy in association with congenital melanocytic nevi is dependent on the size of the nevus; the risk of developing neurocutaneous melanocytosis correlates best with the number of satellite nevi.[26]

 

DDx

Diagnostic Considerations

Also consider the following:

The histopathologic interpretation of proliferative nodules (PNs) in congenital melanocytic nevi can be challenging, as some PNs may exhibit atypical features that make the distinction from melanoma difficult.[28] Histologic features and Ki-67 and PHH3 expression levels were found to be the best parameters to distinguish between benign versus atypical PNs, which appear to be borderline between benign PNs and dermal melanomas. It can be difficult to differentiate between benign and malignant proliferation in infants with secondary melanocytic proliferation.[29] Giant congenital melanocytic nevi with solid tumors within them presenting at birth are unusual; a variety of malignancies may occur within these masses.[30, 31]

A giant congenital melanocytic nevus with vascular malformation and epidermal cysts, associated with a somatic activating mutation in BRAF, has been described.[32]

Differential Diagnoses

 

Workup

Laboratory Studies

Biopsy confirms a benign or malignant nature in suggestive lesions.

Imaging Studies

In cases associated with a high index of suspicion for the presence of neurocutaneous melanosis, magnetic resonance imaging of the central nervous system is a useful diagnostic tool. The presence of a large congenital melanocytic nevus in an infant should prompt magnetic resonance imaging testing before age 4 months if it is in a posterior midline location or is associated with multiple satellite nevi.[23]

Congenital melanocytic nevi rarely involve underlying bones and the maxillary sinus. Such a tumor was documented by magnetic resonance imaging, scintigraphy, and histopathology.[33]

Other Tests

A review of dermoscopy patterns in congenital nevi found that most nevi demonstrate a reticular, globular, or reticuloglobular pattern. The findings varied with age and the anatomic location of the nevus, with the globular pattern found more often in younger children and the reticular pattern found in patients aged 12 years or older.[34]

Histologic Findings

Because of the increased risk of melanoma associated with congenital nevi, attempts have been made to distinguish congenital nevi from acquired nevi on the basis of histology. Distinguishing histologic features include (1) involvement by nevus cells of deep dermal appendages and neurovascular structures (including hair follicles, sebaceous glands, arrector pili muscles, and within walls of blood vessels), (2) extension of nevus cells to deep dermis and subcutaneous fat, (3) infiltration of nevus cells between collagen bundles, and (4) a nevus cell–poor subepidermal zone.[35, 36, 37] Note the images below.

The photomicrograph shows a symmetrical broad prol The photomicrograph shows a symmetrical broad proliferation of melanocytes in the papillary and reticular dermis with maturation with progressive descent; splaying between collagen bundles; and permeation of muscles of hair erection, blood vessels, and adnexa (hematoxylin and eosin stain, 20X magnification).
Higher-power view of the previous image (hematoxyl Higher-power view of the previous image (hematoxylin and eosin stain, 40X magnification).

In contrast to congenital nevi, acquired nevi are usually composed of nevus cells that are limited to the papillary and upper reticular dermis and do not involve the appendages.

 

Treatment

Medical Care

The management of congenital melanocytic nevi depends on a number of factors, including the size of the lesion, the location of the lesion, the age of patient, the effect on cosmesis, and the potential for malignant transformation.

Although the risk of malignant transformation in small and medium-sized congenital melanocytic nevi has not been established, many physicians agree that the risk is probably not significant enough to warrant the prophylactic removal of all of these lesions. However, some patients may desire removal of these lesions to improve cosmesis.[38] Until evidence is presented on which to base definitive treatment guidelines, many physicians are managing small and medium-sized congenital melanocytic nevi with baseline photography and regular follow-up, with frequency dependent upon the clinician's experience and practice.[39]

Surgical Care

Surgical removal of congenital melanocytic nevi is performed for two main reasons, (1) to improve the cosmetic appearance of the patient and (2) to reduce the likelihood of malignant transformation. The increased risk of malignant transformation associated with giant congenital melanocytic nevi is well established. Ideally, these lesions are removed whenever possible. Children with congenital melanocytic nevi of the eyelids and periorbital region may also benefit from early treatment to prevent or minimize disturbance of eyelid function.[40] Barriers to removal may include the size of the lesion and its proximity to vital structures. Several different procedures are available to remove congenital melanocytic nevi.[41] Serial excision can be an effective approach.[42] After excision of a giant congenital melanocytic nevus, recurrent nevi may be evident.[43]

Surgical excision of giant congenital melanocytic nevi, depending on the size and location of the lesion, may be challenging.[44] Often, the size of the lesion necessitates a staged excision. Tissue expanders, tissue grafts, and tissue flaps are often necessary to close the large defects following excision. Cultured skin replacements have also been used in the closure of surgical wounds.[45] Because the melanocytes in such cases may extend deep into underlying tissues (including muscle, bone, and central nervous system), removing the cutaneous component may not eliminate the risk of malignancy. Excision may be facilitated by tissue expansion. Immediate expansion using a Foley catheter may be used in single-stage reconstruction of head and neck defects; it has the advantage of omnidirectional expansion.[46] Alternative strategies may be mandated.[44]

Curettage of the lesions may be performed during the neonatal period,[47] but long-term studies suggest the nevus will, in part, recur. This is likely due to those components of the epidermis that are deep to the level of curettage.

Laser treatment of the lesions has been performed with a number of different types of lasers, including the following systems:

  • High-energy pulsed carbon dioxide laser[48, 49, 50, 51]

  • Erbium:YAG laser[49, 52]

  • Normal-mode ruby laser[49, 53, 54]

  • Q-switched ruby laser[49, 54, 55]

  • Switched alexandrite laser[51, 53, 56]

Because of the lack of penetrance to deeper tissue levels, long-term recurrence is also an issue with these techniques. Laser treatment of congenital melanocytic nevi also remains controversial for a variety of reasons. The effects of sublethal laser fluences on the risk of malignant transformation of melanocytes are uncertain. Additionally, while the destruction of more superficial melanocytes may improve cosmesis, if melanoma does develop in a laser-treated lesion, it may be more likely to occur deeper in the tissue, where it may evade clinical detection until it reaches a more advanced stage.

Consultations

Because of the risk of neurocutaneous melanosis in patients with giant congenital nevi or multiple smaller congenital nevi, consultation with a neurologist, pediatrician, or both may be useful to detect possible early neurologic manifestations of the disease. Even in the absence of malignancy, neurocutaneous melanosis may cause problems such as obstructive hydrocephalus.

Diet

No specific dietary recommendations are necessary for patients with congenital nevi.

Activity

No specific activity restrictions are necessary for patients with congenital nevi. However, because of the increased risk for the development of melanoma, especially in patients with giant congenital nevi, proper protective measures should be taken to minimize ultraviolet light exposure. Maintaining the ability to take part in normal activities should be a consideration when planning surgical removal of a congenital nevus.

Affected children may be stigmatized with psychological maladjustment and need special monitoring and support.[57]