Proliferative nodules of undifferentiated spindle cells arising in a large congenital melanocytic naevus

Proliferative nodules (PN) are benign lesions that arise in large congenital melanocytic naevi (LCMN). Clinically and histologically they can be difficult to differentiate from malignancies, which are also associated with LCMN. The PN in this case consisted of undifferentiated spindle cells and exhibited unusual histological features including negative stains for melanocytic markers (S100, HMB45 and MelA), negative stain for c‐Kit, high mitotic index and unusual morphology of the lesional cells. As a result, a firm histological classification could not be made, which posed a challenge for the clinical management.     

Giant hairy 'bathing trunk' naevus with multiple congenital melanocytic naevi

A 23-day-old male infant had hairy 'bathing trunk' naevus covering, neck and upper trunk along with multiple congenital melanocytic naevi scattered all over the body.     

Activating BRAF mutations in eruptive melanocytic naevi

Background Eruptive melanocytic naevi (EMN) are melanocytic proliferations developing rapidly on previously unaffected skin in association with various clinical scenarios, most commonly systemic immunosuppression. However, the exact mechanism leading to development of EMN is not understood. In particular, it is not known whether EMN harbour the BRAF mutations which occur frequently in melanoma and most common naevi. Objectives To evaluate whether activating BRAF mutations may play a role in genesis of EMN. Methods Genomic DNA was isolated from 20 EMN from a patient treated with 6‐mercaptopurine (6‐MP). Primary BRAF genotyping was performed by allele‐specific polymerase chain reaction, followed by validation using direct sequencing. Results The BRAF V600E mutation was identified in 85% of EMN examined. Conclusions Our results implicate mutational activation of the BRAF–MAPK pathway as a factor in development of EMN in the setting of 6‐MP treatment. The mechanism leading to development of EMN in this, and potentially other patients, may relate to synergistic mutagenic effects of thioguanines and ultraviolet (UV) A. Together with the documented importance of BRAF mutations in melanoma development and maintenance, these findings highlight the importance of UVA protection, especially in patients treated with thiopurines such as 6‐MP.     

Melanoma in congenital melanocytic naevi

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.     

Absence of BRAF and HRAS mutations in eruptive Spitz naevi

Background Eruptive Spitz naevi have been reported rarely in the literature. In solitary Spitz naevi, BRAF and HRAS mutations, as well as increased copy numbers of chromosome 11p have been identified. Objectives To investigate the genetic changes underlying eruptive Spitz naevi. Methods We report on a 16‐year‐old boy who developed multiple disseminated eruptive Spitz naevi within a few months. We analysed BRAF, HRAS, KRAS and NRAS genes in 39 naevi from this patient for hotspot mutations. Furthermore, comparative genomic hybridization analysis was performed in three lesions. Results None of the Spitz naevi displayed a mutation in the analysed genes, and no chromosomal imbalances were observed. Conclusions Our results indicate that the typical genetic alterations described in solitary Spitz naevi appear to be absent in eruptive Spitz naevi. Yet unknown alternative genetic alterations must account for this rare syndrome.     

Multiple congenital melanocytic naevi presenting with neurofibroma-like lesions complicated by malignant melanoma

Giant congenital pigmented naevi and neurofibromatosis (NF-1) may rarely occur together. We report an unusual case where extensive congenital melanocytic naevi were associated with neurofibroma-like lesions that were clinically and histologically confused with neurofibromatosis. The development of malignant melanomas within the pigmented and pendulous lesions representing multiple congenital melanocytic naevi highlights the importance of an accurate diagnosis and a close follow-up of such patients.     

Distribution of congenital melanocytic naevi and congenital naevus-like naevi in a survey of 3406 Italian schoolchildren

Background  Scanty information is available on the prevalence of congenital melanocytic naevi (CMN) and congenital naevus-like naevi (CNLN), particularly the small ones.
Objectives  To estimate the prevalence of CMN/CNLN in Italian schoolchildren, and to assess variations according to potential risk factors for melanoma.
Methods  We conducted a survey in 13 Italian areas on 3406 schoolchildren aged 12–17 years. Children were examined by dermatologists who assessed pigmentary traits and made a count of small (6–15 mm in diameter) and medium/large (> 15 mm) CMN/CNLN on 19 anatomical areas.
Results  Overall, 592 children (17·4%) had one or more CMN/CNLN. Prevalence of small CMN/CNLN was 16·1%, and that of medium/large CMN/CNLN was 1·8%. There was no difference between age groups and sexes. CMN/CNLN were more frequent in children with a higher number of common melanocytic naevi (multivariate odds ratio, OR = 7·1 for the highest vs. the lowest quartile), consistent in small (OR = 7·2) and medium/large CMN/CNLN (OR = 6·0). Family history of malignant melanoma (OR = 1·4) and personal history of diabetes (OR = 4·4) appeared to be directly, and sun exposure inversely associated with CMN/CNLN. No relation was evident between CMN/CNLN and pigmentary traits, anthropometric characteristics, dietary habits, freckles, sunburns, sunscreen use or history of selected diseases.
Conclusions  The association with family history of melanoma, the strong association with acquired melanocytic naevi, and the lack of association with pigmentary traits and sunburns suggest that CMN/CNLN may act as an independent risk marker for subjects at increased risk for cutaneous melanoma later in life.     

Benign melanocytic proliferative nodule within a congenital naevus

A neonate presented with a deeply pigmented papule within a medium-sized congenital naevus. Histologically, this proved to be a benign proliferative nodule in a congenital naevus. This case is presented to highlight the occurrence of this lesion, the main differential of which is the rare entity of true congenital melanoma.     

Desmoplastic hairless hypopigmented naevus: a variant of giant congenital melanocytic naevus

Desmoplasia has been described in melanoma and Spitz naevus but not in giant congenital melanocytic naevus (GCMN). In melanoma desmoplasia is associated with a better survival. Four paediatric patients with hard, ligneous, progressively hypopigmented and alopecic GCMN were seen among 143 cases of GCMN at the Department of Dermatology of the National Institute of Paediatrics, Mexico City. Clinically, induration was progressive in three patients and regressive in one. Pigmentation was regressive in all. Histopathologically, all four patients showed intense dermal fibrosis, scarce naevus cells, and hypotrophic or absent hair follicles. Follow-up and serial biopsies in three patients documented the progressive nature of fibrosis and naevus cell depletion. No evidence of malignant transformation was found. Naevus cell depletion resulted in pigment loss and may have reduced the risk of malignant transformation. Although the cause of fibrosis is unknown, the possibility of an immune reaction to naevus cells is postulated.     

Regressing eruptive disseminated pigmented Spitz (Reed) nevi in a young adult

Eruptive disseminated Spitz nevi is a rare clinical presentation that features an abrupt widespread eruption of Spitz nevi. Spontaneous regression of these nevi has been rarely reported in previous literature. The authors of the present study report the case of a 30-year-old man who presented eruptive disseminated Spitz nevi that appeared within a week and started regression in the following years.     

Melanoma risk in congenital melanocytic naevi: a systematic review

BACKGROUND: The risk of malignant melanoma in congenital melanocytic naevi (CMN) is a matter of controversial and ongoing debate. OBJECTIVES: The purpose of this systematic review is to provide a careful and detailed summary of the published data, including several recently published studies. METHODS: Articles on CMN (n=1424) were retrieved from Medline, 1966-October 2005. Case reports and studies lacking relevant clinical information were excluded. Only systematic collections of cases were taken into consideration. Series with fewer than 20 patients or studies with a mean follow-up of <3 years were regarded as epidemiologically less significant. RESULTS: Fourteen articles were finally chosen for further analysis. The studies varied significantly with respect to study design (source of cases; retrospective vs. prospective analysis), age of patients, follow-up time, and naevus characteristics. The frequency of melanomas ranged between 0.05% and 10.7% and was significantly higher in smaller studies (P<0.0001). In a total of 6571 patients with CMN who were followed for a mean of 3.4-23.7 years, 46 patients (0.7%) developed 49 melanomas. The mean age at diagnosis of melanoma was 15.5 years (median 7). By comparison with age-adjusted data from the Surveillance, Epidemiology and End Results database, we calculated that patients with CMN carry an approximately 465-fold increased relative risk of developing melanoma during childhood and adolescence. Primary melanomas arose inside the naevi in 33 of 49 cases (67%). In seven cases (14%), metastatic melanoma with unknown primary was encountered; in four cases (8%) the melanoma developed at an extracutaneous site. The risk of developing melanoma and the rate of fatal courses were by far highest in CMN>or=40 cm in diameter. CONCLUSIONS: The overall risk of melanoma of 0.7% in all 14 studies was lower than expected. The higher incidence of melanomas in smaller studies indicates selection bias. The melanoma risk strongly depends on the size of CMN and is highest in those naevi traditionally designated as garment naevi. The median age of 7 years at diagnosis of melanoma points to a risk maximum in childhood and adolescence. Future studies on CMN should report: (i) diameter, percentage of body surface, and localization of the CMN; (ii) percentage of naevus area removed by excision or subject to dermabrasion or other superficial treatments; (iii) mean and median age at entry into the study; (iv) mean and median follow-up time; (v) details on each melanoma case; (vi) standardized morbidity ratio of melanoma; and (vii) percentage of neurocutaneous melanosis.     

Psychosocial sequelae in 29 children with giant congenital melanocytic naevi

Giant congenital melanocytic naevus (GCMN) may be expected to affect psychosocial functioning of children and their parents due to deviant appearance and painful treatment. To obtain insight into clinical aspects and psychosocial functioning of those suffering from GCMN, 29 children diagnosed with GCMN syndrome or single GCMN received a dermatological examination, were interviewed, and their mothers and teachers completed standardized questionnaires on the child's competence and behavioural/emotional problems and their own adjustment. Social problems were reported for 30% of the patients and behavioural/emotional problems for 25.9%. There was no correlation between visibility of the naevus, treatment or child age and psychological problems. Mothers reported considerable psychosocial burden. It is concluded that children with GCMN are at increased risk of social and behavioural/emotional problems, and mothers suffer considerable psychological impact of their child's condition.