11/27/13

Congenital Nevi

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Congenital Nevi
Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD more... Updated: Sep 26, 2013

Background
Congenital nevi are present at birth and result from a proliferation of benign melanocytes in the dermis, epidermis, or both. 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] Congenital 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] 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.

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.[3, 4, 5] 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.[6] 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. 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 thefetus itself is unknown as is the application of this finding to non-european and more darkly pigmented races.[7] 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.[8] 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
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Congenital Nevi

lesions are histologically benign.[9] 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.[9] Mutations in NRAS in congenital melanocytic nevi can cause mitogen-activated protein kinase activation and may represent early events in melanoma development.[10] 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.[11]

Epidemiology
Frequency
International 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.[12]

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.[13, 14] 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.[15] Another suggests multiple satellite nevi alone or with associated posterior midline location of large congenital melanocytic nevi is linked with increased risk.[16] 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.

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.

Contributor Information and Disclosures

Author Robert A Schwartz, MD, MPH Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American
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Congenital Nevi

Academy of Dermatology, American College of Physicians, New York Academy of Medicine, and Sigma Xi Disclosure: Nothing to disclose. Coauthor(s) Christopher J Steen, MD Dermatologist, Private Practice Christopher J Steen, MD is a member of the following medical societies: Alpha Omega Alpha and Sigma Xi Disclosure: Nothing to disclose. Jerry Rothenberg, MD Clinical Associate Professor, Department of Dermatology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School; President, Director, New Jersey Dermatopathology Laboratory, Inc Disclosure: Nothing to disclose. Isabelle Thomas, MD Associate Professor, Department of Dermatology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School; Chief of Dermatology Service, Veterans Affairs Medical Center of East Orange Isabelle Thomas, MD is a member of the following medical societies: American Academy of Dermatology and Sigma Xi Disclosure: Nothing to disclose. Specialty Editor Board Franklin Flowers, MD Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, Affiliate Associate Professor of Pediatrics and Pathology, University of Florida College of Medicine Franklin Flowers, MD, is a member of the following medical societies: American College of Mohs Micrographic Surgery and Cutaneous Oncology Disclosure: Nothing to disclose. David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa Disclosure: Nothing to disclose. Jeffrey Meffert, MD Assistant Clinical Professor of Dermatology, University of Texas School of Medicine at San Antonio Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, and Texas Dermatological Society Disclosure: Nothing to disclose. Catherine M Quirk, MD Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology Disclosure: Nothing to disclose. Chief Editor Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
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Disclosure: Nothing to disclose.

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