Atypical nevi

Management Strategy

Differentiating DN from melanoma is the cornerstone of patient management and requires integrating information from multiple sources. The overarching goal in managing patients with DN and AMS is to find early melanoma while minimizing the unnecessary removal of nevi. The level of evidence-strength of recommendation of the various management options of DN is difficult to ascertain due to a paucity of prospective randomized studies.

Achieving the first objective of finding early melanoma requires patients’ and physicians’ vigilance for the presence of any new or changing lesions. Patients should be encouraged to perform self-examination on a periodic basis and if they notice any new, changing, or symptomatic lesions, to bring it to the attention of their physician. In addition, patients should visit their physician on a regular basis, at least annually.

Patient’s profile is vitally important as patients with many nevi including multiple DN or personal or familial history of melanoma are at significantly higher risk for developing melanoma. Personal history of melanoma increases the risk for a subsequent melanoma by 100-fold; history of at least two family members with melanoma increases the risk 200-fold; and, for both personal and family history, the risk increases by 1200-fold.

The skin cancer surveillance examination should involve examining the entire skin surface with dermoscopic evaluation of nevi and baseline photography . Individuals with many nevi can get their entire skin surface imaged. These total body photographs serve as a baseline to which subsequent examinations of the patient are compared to detect new or changed lesions.

Once a lesion of interest has been identified, it can be examined further with dermoscopy to determine if a biopsy is warranted. Clinically distinguishing DN from melanoma using the clinical ABCD rule (Asymmetry, Border irregularity, Color variegation, Diameter >6mm) is of little use since DN and melanoma share the same criteria. Dermoscopy of these lesions can help in distinguishing many DN from melanoma. In addition, the comparative approach, which relies on identifying the dermoscopic signature nevus pattern/s in a given individual and then isolating those lesions that deviate from the signature pattern/s (i.e., outlier lesion or ugly duckling lesion), is another means for finding lesions with a higher pre-test probability for being malignant. Baseline dermoscopy images of individual nevi can also be obtained for future comparison (digital dermoscopic monitoring). Over time these nevi can be examined and compared to their baseline dermoscopic images, with the aim of finding subtle changes that may herald the earliest signs of melanoma. Numerous studies have shown that total body photography and digital dermoscopy contribute to improvements in the clinician’s diagnostic accuracy, both during in-person clinic visits and during teledermatology consultations.

Besides dermoscopy, other in vivo technologies such as reflectance confocal microscopy (RCM), optical coherence tomography, and electrical impedance spectroscopy may also help in differentiating nevi from melanoma. The most studied of these is RCM , which provides horizontal section images of the skin at cellular resolution. These quasi-histology RCM images can further enhance the clinician’s diagnostic accuracy beyond that achieved with dermoscopy alone.

During the initial patient encounter, the dermatologist will need to evaluate all lesions and decide whether any are suspicious for skin cancer, based on patient history or findings noted on clinical-dermoscopic examination. Outlier lesions, lesions deviating from the normal dermoscopic nevus patterns, and lesions manifesting melanoma specific structures on dermoscopy require particularly close attention. Depending on the degree of concern, lesions can be subjected to further investigations with tools such as RCM or imaged for baseline for the purpose of close monitoring or subjected to excisional biopsy if concern for melanoma remains. For patients with AMS, total body photographs and digital dermoscopy imaging should be obtained and used for comparison during subsequent encounters. Longitudinal monitoring of lesions helps identify new and changing lesions with a higher pre-test probability for being melanoma. The monitoring intervals for individual lesions is separated into short-term (3–6-month interval) and long-term (>6-month interval) depending on the degree of concern. For lesions, where the index of suspicion for melanoma is high, a monitoring interval of between 3–6 months is recommended. Any dermoscopic changes noted comparing the baseline dermoscopy image and the follow-up dermoscopy image warrants strong consideration for biopsy. For lesions manifesting a benign clinical and dermoscopy morphology, follow-up intervals of 6–12 months are recommended. Unlike short-term monitoring where the subtlest of changes warrants a biopsy, during long-term monitoring the changes that prompt a biopsy need to be more substantial.

The current recommendation by experts is that individuals at risk for developing melanoma should be screened at least annually. However, depending on the complexity of the examination, the number of nevi, the number of DN, and the history of melanoma, the examination frequency can be a short as 3 months.

Genetic testing should be considered after appropriate genetic counseling of AMS patients who have a strong family history of melanoma. Of all melanoma cases, 5–10% will be found to have one of the known germline mutations associated with familial AMS and melanoma. The most common of these mutations is in CDKN2A , with a frequency of 20–40% among those individuals. However, CDKN2A mutation carriers are not necessarily associated with an AMS phenotype. Individuals with germline CDKN2A mutations are at increased risk for developing mainly melanoma and pancreatic cancer. While there is strong evidence that skin cancer surveillance in these individuals leads to detection of thinner melanomas with improved survival, this cannot yet be said for pancreatic cancer surveillance. Other germline alterations that may be found in a subgroup of AMS patients are the BAP-1 mutations. These individuals are at increased risk for cutaneous melanoma, ocular melanoma, renal cell cancer, and mesothelioma, among other cancers.

The prophylactic excision of DN should be abandoned in favor of targeted excision of only those lesions that cannot be differentiated from melanoma. In such cases it will be necessary to perform a biopsy and the recommended technique, if feasible, is an e xcisional biopsy or deep shave/saucerization removal of the entire lesion with narrow margins. Incisional (partial) biopsy and shallow shave biopsies are discouraged and should only be considered in lesions located in certain anatomic sites such as the nose and eyelids, or in excessively large lesions. If the DN is completely excised with clear margins, no further action is required. However, if the margins of excision are positive, then the question of re-excision of DN to ensure clear margins needs to be addressed, and clinical–dermoscopic–pathologic correlation can prove helpful in shaping clinical management decisions. Clearly, the degree of cytologic atypia influences the management decisions, with DN manifesting severe atypia being reexcised much more commonly than DN manifesting lesser degree of atypia. In general, DN that clinically and dermoscopically display features consistent with melanoma or have severe atypia on histopathology should be re-excised. DN that manifest mild-to-moderate atypia can generally be followed up without the need to reexcise all such lesions.