Search

BACKGROUND: Mutations in the CDKN2A and CDK4 genes predispose to melanoma. From three case-control studies of cutaneous melanoma, we estimated the prevalence and predictors of these mutations for people from regions with widely differing latitudes and melanoma incidence. METHODS: Population-based cases and controls from the United Kingdom (1586 cases, 499 controls) and Australia (596 early-onset cases, 476 controls), and a hospital-based series from Spain (747 cases, 109 controls), were screened for variants in all exons of CDKN2A and the p16INK4A binding domain of CDK4. RESULTS: The prevalence of mutations for people with melanoma was similar across regions: 2.3%, 2.5% and 2.0% for Australia, Spain and the United Kingdom respectively. The strongest predictors of carrying a mutation were having multiple primaries (odds ratio (OR) = 5.4, 95% confidence interval (CI: 2.5, 11.6) for 2 primaries and OR = 32.4 (95% CI: 14.7, 71.2) for 3 or more compared with 1 primary only); and family history (OR = 3.8; 95% CI:1.89, 7.5) for 1 affected first- or second-degree relative and OR = 23.2 (95% CI: 11.3, 47.6) for 2 or more compared with no affected relatives). Only 1.1% of melanoma cases with neither a family history nor multiple primaries had mutations. CONCLUSIONS: There is a low probability (<2%) of detecting a germline CDKN2A mutation in people with melanoma except for those with a strong family history of melanoma (≥2 affected relatives, 25%), three or more primary melanomas (29%), or more than one primary melanoma who also have other affected relatives (27%).

BACKGROUND: The 'gold standard' for the diagnosis of melanocytic lesions is dermatopathology. Although most of the diagnostic criteria are clearly defined, the interpretation of histopathology slides may be subject to interobserver variability. OBJECTIVES: The aim of this study was to determine the variability among dermatopathologists in the interpretation of clinically difficult melanocytic lesions. METHODS: This study used the database of MelaFind®, a computer-vision system for the diagnosis of melanoma. All lesions were surgically removed and sent for independent evaluation by four dermatopathologists. Agreement was calculated using kappa statistics. RESULTS: A total of 1,249 pigmented melanocytic lesions were included. There was a substantial agreement among expert dermatopathologists: two-category kappa was 0.80 (melanoma vs. non-melanoma) and three-category kappa was 0.62 (malignant vs. borderline vs. benign melanocytic lesions). The agreement was significantly greater for patients ≥40 years (three-category kappa = 0.67) than for younger patients (kappa = 0.49). In addition, the agreement was significantly lower for patients with atypical mole syndrome (AMS) (kappa = 0.31) than for patients without AMS (kappa = 0.76). LIMITATIONS: The data were limited by the inclusion/exclusion criteria of the MelaFind® study. This might represent a selection bias. The agreement was evaluated using kappa statistics. This is a standard method for evaluating agreement among pathologists, but might be considered controversial by some statisticians. CONCLUSIONS: Expert dermatopathologists have a high level of agreement when diagnosing clinically difficult melanocytic lesions. However, even among expert dermatopathologists, the current 'gold standard' is not perfect. Our results indicate that lesions from younger patients and patients with AMS may be more problematic for the dermatopathologists, suggesting that improved diagnostic criteria are needed for such patients.

Because melanoma in advanced stages is still incurable, early detection is indispensable to reduce mortality. With the introduction of dermoscopy into the clinical practice, the diagnostic accuracy of pigmented skin lesions can be improved. Dermoscopy is a noninvasive diagnostic technique for the in vivo observation in dermatology. This technique enables the clinician to visualize pigmented structures of the epidermis, dermo–epidermal junction, and papillary dermis, which are not visible to the naked eye. The structures observed by dermoscopy correlate with histopathological findings. Dermoscopy opens a new dimension in the clinical morphology of pigmented skin lesions but diagnostic accuracy depends significantly on the experience of the examiner.

The mechanisms for the development of acquired melanocytic nevi remain mostly unclear. Here we report a case of eruptive nevi that developed after localized superficial trauma, and review the currently known cellular and triggering factors for acquired melanocytic nevi. A 66-year-old woman presented a linear arrangement of pigmented macules on her left calf that developed after a bloodless skin erosion on the same spot, resulting from friction with the lining of a ski boot. Dermatopathology identified multiple junctional proliferations of single or small nest-forming melanocytes with bridging, pigment incontinence and moderate cellular atypia. The number of a person's nevi correlates with age, race and genetics, but blistering diseases, scarring processes, light exposure and immunosuppression can contribute to nevocellular growth as well. Damaged keratinocytes and inflammatory cells can release growth factors inducing nevus cell proliferation, and immunosuppression could end cellular surveillance keeping preexisting nevus cell nests in check. We conclude that in predisposed patients, the trigger for eruptive nevi can be reduced to a simple localized minor trauma.