Melanoma in congenital melanocytic naevi

Abstract

Congenital melanocytic naevi (CMN) are a known risk factor for melanoma, with the greatest risk currently thought to be in childhood. There has been controversy over the years about the incidence of melanoma, and therefore over the clinical management of CMN, due partly to the difficulties of histological diagnosis and partly to publishing bias towards cases of malignancy. Large cohort studies have demonstrated that melanoma risk in childhood is related to the severity of the congenital phenotype. New understanding of the genetics of CMN offers the possibility of improvement in diagnosis of melanoma, identification of those at highest risk, and new treatment options. We review the world literature and our centre's experience over the last 25 years, including the molecular characteristics of melanoma in these patients and new melanoma incidence and outcome data from our prospective cohort. Management strategies are proposed for presentation of suspected melanoma of the skin and the central nervous system in patients with CMN, including use of oral mitogen-activated protein kinase kinase inhibitors in NRAS-mutated tumours.

Figure 1

Benign proliferative nodules, which develop commonly within large congenital melanocytic naevi. (a, b, e) Nodules more typical of the ‘classic proliferative nodule’ type; (d) typical ‘neuroid’ type growths; (c) multiple benign proliferations that are not typical of either category. Written consent was obtained for publication.

Figure 2

Congenital melanocytic naevus (CMN) – histological features in the nervous system (a–e) and skin (f–h). (a, b) Images of leptomeningeal disease showing a cellular collection of melanocytes with minimal atypia and no significant proliferation, confirmed on Ki67 labelling (b) (patient 3, Table 1). (c–e) In contrast, proliferation of markedly atypical cells with frequent mitotic figures and a high Ki67 labelling index (e). The lesion expresses markers of melanocytes (HMB45). (f–h) Areas in a proliferative nodule within a cutaneous CMN demonstrating typical small deep melanocytes admixed with expansile areas formed of spindled cells and areas with larger cells with eosinophilic cytoplasm; there is no significant atypia and no mitoses are seen. H&E, haematoxylin and eosin.

Figure 3

Congenital melanocytic naevus (CMN) – clinical photographs and representative array comparative genomic hybridization traces from chromosome 1 from a new nodule within a scalp CMN that was resected (a, b), but recurred as full‐blown cutaneous melanoma within weeks (c, d) (patient 12 in Table 1). The comparative genomic hybridization data from the nodule demonstrate mosaicism for copy‐number gains and losses, which are then easily seen and called by the program (red and green highlighted areas) in the melanoma sample. The only difference clinically between this nodule and those in Figure 2 was the more rapid rate of growth and failure to stabilize. Written consent was obtained for publication.

Figure 4

Congenital melanocytic naevus (CMN) – management pathways for suspected malignancy. (a) Proposed clinical pathways for investigation of a patient with CMN with new neurological symptoms or signs [possible central nervous system (CNS) melanoma]. (b) Proposed management of a new lump arising in a CMN. 4/52, 4 weeks; CGH, comparative genomic hybridization; FISH, fluorescence in situ hybridization; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; PET, positron emission tomography.