Oncogenic mutations within the MAPK pathway are frequent in melanoma, and targeting of MAPK signaling has yielded spectacular responses in a significant number of patients that last for several months before relapsing. We investigated the effects of two different inhibitors of MAPK signaling in proliferative and invasive melanoma cell cultures with various mutations in the MAPK pathway. Proliferative melanoma cells were more susceptible to pathway inhibition than invasive phenotype cells, irrespective of BRAF mutation status, while invasive phenotype cell response was dependent on BRAF mutation status. Critically, MAPK pathway inhibition of proliferative phenotype cells resulted in acquisition of invasive phenotype characteristics. These results show that melanoma cell phenotype is an important factor in MAPK pathway inhibition response. This suggests that while current therapeutic strategies target proliferative melanoma cells, future approaches should also account for the invasive phenotype population.

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Cutaneous AS was clinically diagnosed in 4 of 9 patients, while systemic lupus erythematosus was the most common misdiagnosis. Radiotherapy was the most prescribed treatment, but many different combinations of surgery, chemotherapy and radiotherapy were observed. Mean disease-free and overall survival (15.4 and 23.7 respectively) were consistent with previous series, with local recurrence rate (2/9) lower than previously reported data. CD31 was positive in all patients. Vimentin, D2-40 and VEGFR-3 were expressed by the vast majority, Factor VIII by 3/7 and CD34 by about 1/3 of patients. Cytokeratin was negative in all patients. The patients with the most unfavourable course showed a strong expression of Ki-67, while those with the best outcome only had a slight positive Ki-67 staining. Larger studies regarding tumour cell expression of Ki-67 and other markers such as D2-40 will be helpful to evaluate a potential prognostic value of these stainings.

Background: The incidence and mortality of malignant melanoma have been rising during the past decades, the latter being due to the high invasion capacity and the metastatic potential of melanoma cells to distant organs. Objective: We investigated the distribution pattern of melanoma metastases taking into account different clinicopathological subtypes of melanoma. Methods: We studied 310 stage IV (AJCC 2009) melanoma patients retrospectively with regard to potential correlations between frequency and occurrence of metastasis and the genetic background and pathological/clinical melanoma subtypes. For all patients, the time to distant metastasis (TTDM) and the distribution patterns of metastases were analyzed and correlated to the median survival time. Results: Superficially Spreading (SSM) and Nodular melanomas (NMM) spread to the brain more frequently than Acrolentiginous (ALM) and Mucosal (MM) melanomas (p = 0.0012). The preference to affect the skeleton was significantly higher for ALM and MM in comparison to SSM and NMM (p = 0.0049). Lentigo maligna (LMM) tumors showed a significantly lower metastatic spread to distant lymph nodes (p = 0.0159). BRAF mutant versus wildtype tumors showed no significant differences concerning localization of metastasis but patients with BRAF mutant tumors were significantly younger at primary diagnosis and had a significantly shorter stage IV survival (p = 0.0106). Conclusion: This study shows a clear distinction of melanoma subtypes with regard to metastasizing preferences. Further knowledge about melanoma subtype specific characteristics, including molecular markers predictive of homing preferences, may help to understand and manage this heterogeneous disease in terms of prognosis and follow-up procedures.

To cite this article: Schoenewolf NL, Hafner J, Dummer R, Bogdan Allemann I. Laser treatment of solar lentigines on dorsum of hands: QS Ruby laser versus ablative CO 2 fractional laser -a randomized controlled trial. Eur J Dermatol 2015; 25(2): 122-6Background: Lentigines solares (LS) on the dorsum of hands are often esthetically disturbing. Q-switched ruby laser treatment is highly effective in the treatment of these lesions. Ablative fractional photothermolysis may be a suitable alternative. We compared the Q-switched ruby laser with ablative CO 2 fractional photothermolysis for the treatment of solar lentigines. Objective: To evaluate the efficacy and side-effects of 694nm Q-switched ruby laser (Sinon) with the ablative 10,600nm CO 2 fractional laser (Quantel Excel O2) in an intra-individual side-to-side comparison in the treatment of LS on the dorsum of hands. Material and methods: Eleven patients were included in the study. The hands of each patient were randomized for treatment with the two laser systems. Three treatment sessions were scheduled at weeks 0, 4 and 8. Evaluations by patients, treating physician and blinded experts were scheduled at weeks 0, 4, 8, 16 and 24. Results: The Q-switched ruby laser was significantly more efficacious than the ablative CO 2 fractional laser for removing LS on the dorsum of hands (p = 0.01). Conclusion: In this first study on this topic, the Q-switched ruby laser was superior to the ablative CO 2 fractional laser in the treatment of lentigines solares on the dorsum of hands.