EPILUMINESCENCE microscopy (ELM; in vivo cutaneous surface microscopy, dermoscopy, dermatoscopy, and magnified oil immersion diascopy) is an in vivo, noninvasive technique that has disclosed a new dimension of the clinical morphologic features of pigmented skin lesions using different incident light magnification systems with an oil immersion technique.¹

Purpose: The prevalence of BRAF, NRAS, and p16CDKN2A mutations during melanoma progression remains inconclusive. We investigated the prevalence and distribution of mutations in these genes in different melanoma tissues. Patients and Methods: In all, 291 tumor tissues from 132 patients with melanoma were screened. Paired samples of primary melanomas (n = 102) and synchronous or asynchronous metastases from the same patients (n = 165) were included. Tissue samples underwent mutation analysis (automated DNA sequencing). Secondary lesions included lymph nodes (n = 84), and skin (n = 36), visceral (n = 25), and brain (n = 44) sites. Results: BRAF/NRAS mutations were identified in 58% of primary melanomas (43% BRAF; 15% NRAS); 62% in lymph nodes, 61% subcutaneous, 56% visceral, and 70% in brain sites. Mutations were observed in 63% of metastases (48% BRAF; 15% NRAS), a nonsignificant increase in mutation frequency after progression from primary melanoma. Of the paired samples, lymph nodes (93% consistency) and visceral metastases (96% consistency) presented a highly similar distribution of BRAF/NRAS mutations versus primary melanomas, with a significantly less consistent pattern in brain (80%) and skin metastases (75%). This suggests that independent subclones are generated in some patients. p16CDKN2A mutations were identified in 7% and 14% of primary melanomas and metastases, with a low consistency (31%) between secondary and primary tumor samples. Conclusion: In the era of targeted therapies, assessment of the spectrum and distribution of alterations in molecular targets among patients with melanoma is needed. Our findings about the prevalence of BRAF/NRAS/p16CDKN2A mutations in paired tumor lesions from patients with melanoma may be useful in the management of this disease.

We have used nonlinear imaging to evaluate collagen organization in connective tissue ex‐vivo samples. Image analysis methods were tested on healthy dermis, normal scars, and keloids. The evaluation of the second harmonic to autofluorescence aging index of dermis (SAAID) has allowed a first characterization of tissues by scoring the collagen/elastin content. Further analyses on collagen morphology in healthy dermis and keloids were performed by image‐pattern analysis of SHG images. The gray‐level co‐occurrence matrix (GLCM) analysis method has allowed classification of different tissues based on the evaluation of geometrical arrangement of collagen fibrillar bundles, whereas a pattern analysis of the FFT images has allowed the discrimination of different tissues based on the anisotropy of collagen fibers distribution. This multiple scoring method represents a promising tool to be extended to other collagen disorders, as well as to be used in in‐vivo skin‐imaging applications.

Epidemiological and clinical studies have linked psychosocial factors such as chronic stress and depression with cancer progression and, to a lesser extent, cancer onset.^1-3 The results of experiments conducted in vitro confirm the assumption that stress is a cofactor in melanoma progression.⁴ Moreover, preclinical studies have shown that β-blockers and propranolol in particular inhibit angiogenesis and disrupt migration of cancer cells via inhibition of noradrenaline-dependent responses.^5-7 The first article describing the use of β-blockers in patients with melanoma was published by De Giorgi et al.⁸ In this study, after a median follow-up of 2.5 years, 34% of patients not using β-blockers had evidence of disease progression, while only 3% of those who used β-blockers (administered for other diseases) at the time of diagnosis showed melanoma progression. Thus, we conducted a prospective study in patients with melanoma in our center to compare those treated with propranolol for off-label use with those not treated. We designed 2 cohorts of patients with stage IB to IIIA melanoma, for whom no standard treatment is available, to verify the role of off-label propranolol on melanoma recurrence and mortality. Propranolol was chosen among the nonselective β-blockers because it has been shown to exhibit anticancer effects in cancer cell lines, animal models, and in the majority of studies published in the literature. In addition, the recent observation that propranolol successfully treated cases of infantile hemangioma⁹ and simultaneously reduced vascular endothelial growth factor levels further supported our decision to use a nonselective β-blocker for this off-label treatment.