MOST MELANOMA ARISE DENOVO

Contrary to a widely held assumption, only a minority of melanomas arise in conjunction with a preexisting nevus, commonly referred to as skin moles. The finding comes from an extensive review and meta-analysis of the literature and provides further evidence that most melanomas do not originate as malignant transformations of nevus cells, say the authors.

"It's extremely important to be aware that the majority of melanomas arise de novo because it implies that any newly appearing lesion in adults should be regarded as suspicious," senior author Caterina Longo, MD, PhD, University of Modena and Reggio Emilia, Italy, told Medscape Medical News in an email.

"The practical implication is that both patients and doctors should check all skin carefully, and any newly appearing lesion in adults should be regarded as malignant," she added.

The study was published online August 29 in the Journal of the American Academy of Dermatology.

Under lead author Riccardo Pampena, MD, Arcispedale Santa Maria Nuova, Instituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy, the investigators reviewed 38 studies involving 20,126 melanomas.

In this series, 29.1% of melanomas were associated with a preexisting nevus; thus, 70.9% of the melanomas reviewed had arisen de novo.

"Any given melanoma was 64% less likely to be nevus-associated than de novo," the study authors note (P < .001).

Patients whose melanomas arose from a preexisting nevus were significantly younger, by approximately 4.9 years, than those whose melanomas appeared as new lesions on the skin (P < .001). No significant sex differences in the incidence of either type of melanoma were observed.

Nor were there any differences between melanomas arising from a preexisting nevus and those arising de novo in either histologic subtype or the site at which they appeared on the body.

"Superficial spreading melanoma was the most frequent histologic subtype, and the trunk and extremities were the most common locations reported in both groups," Dr Pampena and colleagues observe.

In those studies in which melanomas were characterized by Breslow thickness, the researchers found that melanomas from a preexisting nevus were thinner than those arising de novo, with a mean difference of -0.39 mm (P = .003). Dr Longo noted that this difference might be explained by the fact that patients with many moles are often screened more regularly by a dermatologist for signs of dysplastic changes in their moles.

Patients with a large number of moles are also more likely to be aware that they need to inspect their own nevi frequently and to notice even small changes in their moles compared to patients whose melanomas appear as new lesions on the skin.

Only 13 of the 38 studies reviewed made a distinction between congenital and acquired nevi. Despite this limitation, Dr Pampena and colleagues found that 77.4% of nevus-associated melanomas were linked to acquired nevi, vs 22.6% of melanomas that were associated with congenital nevi.

Only 15 studies reported information as to whether nevus remnants were dysplastic or nondysplastic, but among those studies with this information, the investigators found slightly more nondysplastic remnants, at 56.7%, compared with 43.3% with dysplastic remnants.

There was also a slight though nonsignificant trend for melanomas arising from preexisting nevi to be associated with nondysplastic nevi relative to dysplastic nevi.

Mean Follow-up of 9 Years

"From information available in 28 studies, the mean follow-up time was found to be 9.3 years," the study authors note. Only two studies reported survival rates for both types of melanomas. Both of those studies suggested that there was a survival advantage for patients whose melanomas arose from preexisting nevi.

However, others have not found any difference in survival for patients with a nevus-associated melanoma compared to those whose melanomas appear as new lesions on the skin.

Dr Longo noted that the lessons learned from this analysis are fairly straightforward. First, general practitioners should apply the "EFG" rule — elevation, growing, firm — as well as taking into consideration other risk factors in selecting patients for referral to a dermatologist.

Dermatologists should also carefully check patients' skin from top to toe," Dr Longo noted, "and in particular, they should carefully check patients with a high number of nevi who are at higher risk to develop a melanoma, even though this melanoma would probably not be nevus-associated," she added.

Dr Longo also emphasized that digital dermoscopic monitoring is required for patients with a large number of nevi in order to avoid "overcalling" melanomas.

And she underscored how important it is for everyone to familiarize themselves with all of their own moles and not only to look for changes in existing moles but also to inspect the skin for any new lesions.

The study was supported by the Italian Ministry of Health. The authors have disclosed no relevant financial relationships. 

J Am Acad Dermatol. Published online August 29, 2017. Abstract