Prognosis

With the exception of giant congenital melanocytic nevi, the majority of nevi are common conditions with a benign course. The most important differential is melanoma, which has some overlapping features clinically and histologically with benign melanocytic nevi, particularly dysplastic or Clark nevi. Despite this, most melanomas arise de novo, and prophylactic removal of nevi is not recommended.[32][47][48][86] Patients with risk factors for nevi are likely to share multiple risk factors for melanoma and nonmelanoma skin cancers, and therefore should be screened appropriately.

Outcome in high-risk patients

Patients with multiple risk factors for nevi including multiple dysplastic nevi, fair skin and eyes, freckling, and predisposition to burn share risk factors with those at risk of skin cancer, and therefore deserve routine skin exams to screen for melanoma and other nonmelanoma skin cancers. As of 2007, the estimated lifetime risk of a person in the US developing an invasive melanoma was 1 in 63, and 1 in 33 overall if in-situ melanomas are included.[73] Melanoma is the most common form of cancer for young adults from 25 to 29 years old and the second most common cancer in adolescents and young adults from 15 to 29 years old.[87] If detected and treated in the early stages before it has spread to the lymph nodes, melanoma has a 99% 5-year survival rate.[72]

Giant congenital nevi

Large or giant congenital melanocytic nevi are rare, often truncal, and defined as >20 cm in their largest dimension. They are associated with about a 2% to 6% lifetime risk of melanoma.[5][6][16][52][88] This risk appears to be greatest in the first 10 years of life. Signs suggestive of melanoma include sudden rapid growth, nodularity, irregular margins and texture, and color variation. Additionally, these nevi confer an increased risk of neurocutaneous melanosis, including leptomeningeal involvement, which may cause central nervous system (CNS) signs (e.g., increased intracranial pressure, mass lesions, or spinal cord compression). Surgical removal cannot eliminate the risk of melanoma in these nevi, as in 50% of cases the melanoma develops in deeper structures, with the CNS being the most common extracutaneous site. Axial location and multiple satellite nevi appear to increase the risk of melanoma. Although there are case reports of malignant transformation in congenital nevi 19.9 cm or less in size, the occurrence has not been quantified and is rare, so prophylactic removal of small and medium congenital nevi is not recommended.[52]

Spitz nevi

Current management of Spitz nevi is driven primarily by the clinician’s experience and comfort level, expert opinion, and the fear of missing a spitzoid melanoma. It is not based on a high level of evidence and there are no guidelines.

Differentiating Spitz nevi from spitzoid melanoma is challenging, even with advances in molecular diagnostics. Spitz nevi frequently harbor histopathological findings that are associated with melanomas, therefore the management of these nevi is more aggressive.

Atypical spitzoid tumors are a heterogeneous group of melanocytic neoplasms for which pathologists cannot accurately and confidently assign true biological potential.[89] Interobserver reproducibility in the diagnosis of atypical Spitz tumor is low, indicating that the threshold for assigning a spitzoid melanocytic neoplasm as atypical varies significantly among pathologists. The rare cases of atypical spitzoid tumor with poor outcomes represent misclassified melanomas. Atypical Spitz tumors are more aggressively managed than Spitz nevi, with some advocating sentinel node biopsy even though there is no proven clinical benefit.

Spitzoid neoplasms should be managed on a case-by-case basis. Spitz nevi are relatively more common in children than in adults. Spitz nevi with typical clinical appearance in children can be conservatively managed: reassure the patient and parent(s)/carer(s), and/or monitor the lesion. An excisional biopsy or a full excision should be attempted if the decision is taken to remove a Spitz nevus for reasons of symptoms or cosmesis. Because the vast majority of atypical spitzoid tumors in children behave in a benign fashion, complete excision with clinical follow-up is reasonable.[90][91][92] The pretest probability of spitzoid melanoma is higher in adults, therefore Spitz nevi are typically completely excised whenever they are encountered. For atypical spitzoid tumors in adults, a sentinel biopsy should be considered only in select lesions in which there is a high index of suspicion for spitzoid melanoma.

Atypical, dysplastic, or Clark nevi

There are practitioners who advocate the notion that dysplastic nevi are both a marker and a precursor lesion to melanoma.[86][93] Although dysplastic nevi may identify people who have an increased risk of melanoma, and therefore may be a marker for such a risk, the notion that they are a precursor lesion is highly controversial and is not widely accepted.[7][17][31][47][48]

Dysplastic nevi represent one of several physical traits commonly found in individuals who have an increased risk of developing melanoma compared with the population at large. Other traits include fair skin (and thus frequent sunburn), freckles, and red hair. In other words, these traits tend to cosegregate with dysplastic nevi. Dysplastic nevi are extremely common in white people, and familial kindreds with multiple lesions are frequently observed. These patients have been dubbed as having familial dysplastic nevus syndrome (or familial atypical mole melanoma syndrome). These patients have been the center of attention for dermatologists because of their higher relative risk of developing melanoma.[47][74][94] Families with multiple dysplastic nevi, however, need to be differentiated from families with hereditary melanoma, whose members are near-certain to develop melanoma in their lifetime.[47][94][95] Fortunately, hereditary melanoma syndrome is exceedingly rare. Family pedigree in these families will reveal the alarming rate of melanomas and deaths in the immediate family members, usually at a very young age.[47][95] In these families, the regulatory protein CDKN2A has been found to be mutated, but this finding has not been a universal one in all familial kindreds of hereditary melanoma, and studies have not found that the presence of the mutation correlates with the presence of dysplastic nevi.[32][47] The risk of melanoma may approach 100% in these patients.[32] Considering the rarity of the mutation, its use as a screening tool would be low-yield and expensive.

Indiscriminate removal or biopsy of dysplastic nevi is not recommended even by those who believe that dysplastic nevi are precursor lesions, because the vast majority are stable.[32][47][86] The designation "Clark nevi" is preferred by those who do not agree that they are precursors, to emphasize that these nevi are but one of many types of nevi encountered.[17][47] For practicing clinicians, dysplastic nevi may at times be difficult to distinguish from early flat melanomas. Familiarity with the morphologic spectrum of dysplastic nevi and their diagnostic pitfalls is essential to manage these patients appropriately. If the clinician is unfamiliar in managing these lesions, referral to more experienced hands should be considered.

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