Search

The genotypic profile of rare amelanotic melanomas (AMs) has been poorly investigated, thus preventing either an accurate identification as a distinctive melanoma subtype or therapy stratification. Here, we investigated the presence of the BRAF(V600E) mutation by real-time quantitative PCR and KIT mutations (exons 11 and 17) by sequencing analysis in 33 AMs. AMs included 'truly' amelanotic lesions (n = 19), with no melanin pigmentation upon dermoscopic inspection and hypomelanotic lesions (n = 14), by definition partially pigmented lesions showing a melanin pigmentation area of less than 25% of the total surface area. The frequency of the BRAF(V600E) mutation was 70.3% in the 33 cases, a percentage that increased to 89% when only the subgroup of thin melanomas (≤ 1 mm in thickness, n = 9) was considered. KIT mutations were found in 12.1% of AMs, all of which developed in nonacral sites. The identification of a relatively high frequency of BRAF(V600E) and KIT mutations in AMs may have important consequences for implementation of the novel targeted therapies now available to treat this life-threatening disease.

Controversies exist regarding the true incidence and significance of the histological association between melanocytic naevi and melanomas. The current study was undertaken to determine the incidence of melanocytic naevi histologically associated with melanomas, to compare the clinicopathological profiles of melanomas associated with a naevus (MN+) and melanomas not associated with a naevus (MN-), and to verify the interobserver reliability of classifying the naevus remnants as congenital or acquired. We evaluated 131 patients with invasive melanoma < or = 4 mm in thickness with a Clark's level < V. Histological evidence of an associated melanocytic naevus was found in 27 out of 131 melanoma cases (20.6%). MN+ were significantly more frequent among males compared with MN-(P = 0.002) and were predominantly located on the trunk (P =0.001). No significant differences between MN+ and MN- were found in the distribution of histotype, Clark's level and thickness. Among MN-, the naevus component showed acquired features in 14 cases (51.8%), whereas 12 cases (44.5%) had features of small superficial congenital naevi; in one case (3.7%) a confident distinction between congenital and acquired naevus could not be made. Overall, there was concordance among the three observers in the diagnosis of the type of naevus remnants in 81.4% of cases (kappa = 0.78; P<0.0001). We conclude that, although the majority of cutaneous melanomas arise de novo, in approximately 20% of cases an associated melanocytic naevus is found. Our observation that MN+ and MN- have different clinicopathological profiles suggests that, at least for some cases, a causal relationship between the two lesions may be present. However, when the naevus is histopathologically adjacent to the melanoma, the possibility of a collision event cannot be ruled out. Finally, we documented a significant concordance among examiners in the diagnosis of the congenital versus acquired nature of the associated naevus. This suggests that the histopathological criteria generally employed to distinguish between congenital and acquired naevi have good reproducibility.