Eruptive Melanocytic Nevi: A Review.

Eruptive melanocytic nevi (EMN) is a phenomenon characterized by the sudden onset of nevi. Our objective was to compile all published reports of EMN to identify possible precipitating factors and to evaluate the clinical appearance and course. We conducted a systematic bibliographic search and selected 93 articles, representing 179 patients with EMN. The suspected causes were skin and other diseases (50%); immunosuppressive agents, chemotherapy or melanotan (41%); and miscellaneous, including idiopathic (9%). The clinical manifestations could largely be divided into two categories: EMN associated with skin diseases were frequently few in number (fewer than ten nevi), large, and localized to the site of previous skin disease, whereas those due to other causes presented most often with multiple small widespread nevi. In general, EMN seem to persist unchanged after their appearance, but development over several years or fading has also been reported. Overall, 16% of the cases had at least one histologically confirmed dysplastic nevus. Five cases of associated melanoma were reported. We conclude that the clinical appearance of EMN may differ according to the suggested triggering factor. Based on the clinical distinction, we propose a new subclassification of EMN: (1) widespread eruptive nevi (WEN), with numerous small nevi, triggered by, for example, drugs and internal diseases, and (2) Köbner-like eruptive nevi, often with big and few nevi, associated with skin diseases and most often localized at the site of previous skin disease/trauma. The nature of the data precluded assessment of risk of malignant transformation.

Trajectories of premalignancy during the journey from melanocyte to melanoma.

A stepwise progression from melanocytic precursors to cutaneous melanoma is a well-established model, based on decades of careful observation and morphological analysis. The steps identified are benign melanocytic naevus, dysplastic naevus, 'radial growth phase' melanoma (including melanoma in situ) and 'vertical growth phase' melanoma (also termed tumourigenic melanoma). Recent genomic data have refined the understanding of the steps of melanoma development and their relationship to one another. These data support the existence of dysplastic naevi as distinct lesions; suggest the importance of clonal dynamics in the precursor steps of melanoma; and confirm the carcinogenic role of ultraviolet radiation throughout early melanoma development and progression. In this review, the steps of melanoma development and progression are summarised and discussed in the context of recent genomic studies. This new understanding of melanoma pathogenesis that has been facilitated through careful correlation of morphological and molecular features will allow the identification and development of robust biomarkers to assist in more accurate diagnosis and prognostication of melanocytic tumours.

Stress and melanoma: increasing the evidence towards a causal basis.

Melanoma is a multifactorial disease with a strong genetic component and known risk factors such as excessive ultraviolet exposure, intermittent sunburns and fair skin type. The prognosis is poor if diagnosis is delayed, in spite of recent treatment advances. Evidence is mounting that the incidence of melanoma is higher in the immunosuppressed and individuals with highly stressful occupations. We present a case series of individuals diagnosed with multiple cutaneous melanomas over a few months to 1 year. All had encountered psychological stressors in their lives, and the melanomas were diagnosed briefly after encountering these stressors. No known causes of immunosuppression were detected to explain the sporadic occurrence of melanomas in these individuals. There is evidence in the current literature that stress can lead to immune disregulation, predisposing an individual to various disease states including melanoma. Stress hormones such as norepinephrine have been shown to cause upregulation of cytokines such as Interleukin 6 and 8, which are proangiogenic and support tumour progression. Coupled with genetic and environmental factors, stress appears to play a role in melanoma formation and progression. Large prospective studies are required to study the link between stress and melanoma and gain further insight into the etiology of melanoma.

Dysplastic nevi and melanoma.

Dysplastic nevi are described as being on a continuum between common acquired nevi and melanoma because they are morphologically and biologically intermediate between these 2 entities. Since initially being reported as histologic lesions observed in melanoma-prone families, there has been considerable debate about the definition of dysplastic nevi, the histologic and clinical criteria used to define them, and their biologic importance. Their role as precursor lesions for melanoma is not their primary role in their relationship to melanoma because of the rarity of transformation of any individual nevus to a melanoma. Although there is still no single, universally agreed upon histologic or clinical definition or even name for these nevi, dysplastic nevi should be considered important because of their association with an increased risk for melanoma.

The "dysplastic" nevus.

Dysplastic nevi have become an increasing focus clinically, with evidence that they are associated with a higher risk of developing melanoma. However, there still is contention regarding the significance of dysplastic nevi. This contribution provides an overview of the history, epidemiology, genetics, clinical and histologic features, and procedures for clinical management of dysplastic nevi. Since dysplastic nevi were described originally in 1978, a great deal of research has examined the epidemiology of these lesions and the genetic factors related to the development of dysplastic nevi. However, there is disagreement regarding the clinical management of dysplastic nevi and the histologic definition of dysplastic nevi. Current recommendations include preventative measures, such as sun protection and careful surveillance and biopsies of suspicious lesions as needed. The advent of new technologies, such as computer-vision systems, have the potential to significantly change treatment of dysplastic nevi in the future.

Dysplastic naevi: to shave, or not to shave? A retrospective study of the use of the shave biopsy technique in the initial management of dysplastic naevi.

The management of dysplastic naevi is a controversial subject. This study sought to assess the usefulness of the shave biopsy technique in the initial management of dysplastic naevi, and to demonstrate the advantages over the punch biopsy technique. We report a retrospective observational study of histopathology specimens examined in one histopathology practice over a 14-month period. Patients who had a clinical diagnosis of 'dysplastic naevus', which had initially been biopsied using either a shave or punch biopsy, and then followed up with a full-thickness elliptical excision, were included in the study. Histopathological concordance between the shave and punch biopsy specimens and their respective follow-up elliptical excisions was compared. We found that 21 of 22 (95.5%) shave biopsies were concordant with their respective excision specimens, and that 29 of 41 (70.7%) punch biopsies were concordant with their respective elliptical excision specimens. Of the shave biopsy specimens reviewed, 66% showed that the dysplastic naevi were completely excised with the initial biopsy, compared with 21.2% of the punch biopsy specimens. These findings confirm that shave biopsies provide accurate diagnostic information in the assessment of dysplastic naevi. Shave biopsies enable the entire lesion to be submitted for histopathological assessment, improving the chances of an accurate diagnosis.

Meta-analysis of risk factors for cutaneous melanoma: I. Common and atypical naevi.

A systematic meta-analysis of observational studies of melanoma and one of the most important risk factors, the number of naevi, was conducted in order to clarify aspects of the aetiology of this disease. Following a systematic literature search, relative risks (RRs) were extracted from 46 studies published before September 2002. Dose-response random effects models were used to obtain pooled estimates. Sub-group analysis and meta-regression were carried out to explore sources of between-study variation and bias. Sensitivity analyses investigated the reliability of the results and any publication bias. Number of common naevi was confirmed an important risk factor with a substantially increased risk associated with the presence of 101-120 naevi compared with <15 (pooled Relative Risk (RR) = 6.89; 95% Confidential Interval (CI): 4.63, 10.25) as was the number of atypical naevi (RR = 6.36 95%; CI: 3.80, 10.33; for 5 versus 0). The type of study and source of cases and controls were two study characteristics that significantly influenced the estimates. Case-control studies, in particular when the hospital was the source for cases or controls, appeared to present much lower and more precise estimates than cohort studies.

Ocular pigmented findings in patients with dysplastic naevus syndrome.

There is a growing body of evidence supporting the theory that cutaneous dysplastic naevus syndrome patients are at increased risk of developing not only skin but also uveal melanoma. The relationship between dysplastic naevus syndrome and ocular naevi needs to be clarified. In this study we investigated the ocular pigmented findings in patients with dysplastic naevus syndrome and compared the results with a control group (subjects without atypical moles) in order to investigate the frequency of ocular naevi among dysplastic naevi-bearing patients. A total of 152 dysplastic naevus syndrome patients were enrolled in our investigation. The control group consisted of 142 sex-, age- and skin type-matched healthy volunteers without cutaneous dysplastic naevi or skin melanoma. Conjunctival and uveal pigmented findings and iris colour were recorded during a detailed ophthalmic examination. A greater number of conjunctival naevi (3.2% versus 0%), iris naevi (5.2% versus 1.4%), iris freckles (17% versus 5.6%) and choroidal naevi (5.2% versus 0.7%) were detected in the dysplastic naevus syndrome group compared with the controls. The difference reached statistical significance in the case of conjunctival naevi, choroidal naevi and iris freckles. Our results confirm the hypothesis that dysplastic naevus syndrome patients might have overstimulation of their melanocytic system not only in the skin but also in the uvea, leading to increased benign (as well as rarely malignant) melanocytic proliferation. Dysplastic naevus syndrome patients should be screened by ophthalmologists because of the increased frequency of different ocular pigmented alterations.

Nevos de Spitz múltiples agminados hemifaciales / Multiple agminated hemifacial Spitz nevi

El nevo de Spitz es habitualmente una lesión solitaria benigna. La aparición de múltiples lesiones agrupadas (nevos de Spitz agminados) es muy rara. Describimos un ejemplo de una niña de 2 años con múltiples nevus de Spitz agrupados en la mitad izquierda de la cara (AU)

UV induction of cyclobutane thymine dimers in the DNA of cultured melanocytes from foreskin, common melanocytic nevi and dysplastic nevi.

We compared the induction of cyclobutane thymine dimers after exposure to 302 nm UV in foreskin-derived melanocytes and melanocytes from nevocellular nevi, as well as in melanocytes cultured from dysplastic nevi, precursor lesions of melanoma, derived from four, three and four individuals, respectively. Cyclobutane thymine dimers were quantified in situ by means of an immunofluorescence assay with a specific monoclonal antibody. A method was developed to compare separately performed experiments in a standardized manner. For melanocytes from each source, we demonstrated a linear relationship between UV dose and immunofluorescence. In nevocellular and dysplastic nevi, two subpopulations could be detected, distinguished by their nuclear size. Large nucleated nevocellular nevus cells were most susceptible to the induction of thymine dimers (49% higher induction compared to induction in foreskin melanocytes), while in normal-sized nuclei of these nevus cells the same induction of thymine dimers was found as in nuclei from foreskin melanocytes. In contrast, large nucleated dysplastic nevus melanocytes did not differ from the foreskin melanocytes, while normal-sized nuclei of dysplastic nevus cells showed a lower induction (32% lower induction than in foreskin melanocytes).