Skin cancers are the most frequent cancers in fair-skinned populations, but we can prevent them.

Cancers of the skin are the most commonly occurring cancers in humans. In fair-skinned populations, up to 95% of keratinocyte skin cancers and 70-95% of cutaneous melanomas are caused by ultraviolet radiation and are thus theoretically preventable. Currently, however, there is no comprehensive global advice on practical steps to be taken to reduce the toll of skin cancer. To address this gap, an expert working group comprising clinicians and researchers from Africa, America, Asia, Australia, and Europe, together with learned societies (European Association of Dermato-Oncology, Euromelanoma, Euroskin, European Union of Medical Specialists, and the Melanoma World Society) reviewed the extant evidence and issued the following evidence-based recommendations for photoprotection as a strategy to prevent skin cancer. Fair skinned people, especially children, should minimise their exposure to ultraviolet radiation, and are advised to use protective measures when the UV index is forecast to reach 3 or higher. Protective measures include a combination of seeking shade, physical protection (e.g. clothing, hat, sunglasses), and applying broad-spectrum, SPF 30 + sunscreens to uncovered skin. Intentional exposure to solar ultraviolet radiation for the purpose of sunbathing and tanning is considered an unhealthy behaviour and should be avoided. Similarly, use of solaria and other artificial sources of ultraviolet radiation to encourage tanning should be strongly discouraged, through regulation if necessary. Primary prevention of skin cancer has a positive return on investment. We encourage policymakers to communicate these messages to the general public and promote their wider implementation.

"White" network in Spitz nevi and early melanomas lacking significant pigmentation.

BACKGROUND: Spitz nevi and early melanomas lacking significant pigmentation exhibit overlapping dermoscopic patterns of regularly arranged dotted vessels over a pink background. Although white network has been described in both tumors, little is known about the frequency of this pattern in both tumors. OBJECTIVE: We sought to compare the frequency of white network in Spitz nevi and early melanomas lacking significant pigmentation and to correlate this feature with histopathology. METHODS: Two independent dermoscopists scored the presence of white network in a series of retrospectively collected images of histopathologically diagnosed cases of Spitz nevi and melanomas, dermoscopically typified by dotted vessels. RESULTS: A total of 65 cases including 39 melanomas (median thickness 0.4 mm) and 26 Spitz nevi were analyzed. Patients with Spitz nevi were significantly younger compared to patients with melanoma (mean age: 26.8 vs 51.2 years, respectively; P < .001). The 2 observers scored white network being present in 23 (88.5%) and 24 (92.3%) Spitz nevi compared with 10 (25.6%) and 8 (20.5%) cases of 39 melanomas, respectively (P < .001). Interobserver agreement for white network was good (kappa = 0.67; 95% confidence interval 0.44-0.90). Histopathologically, elongated rete ridges were observed in 22 (88.5%) Spitz nevi and 11 (36.7%) melanomas (P < .001). LIMITATIONS: We did not evaluate other dermoscopic-histopathologic correlates commonly seen in Spitz nevi and melanomas in our study. CONCLUSION: Although white network occurs at significantly higher frequency among hypopigmented/amelanotic Spitz nevi compared with early melanoma, it is not exclusively seen in Spitz nevi. Thus, excision of melanocytic tumors showing this pattern is mandatory.

Negative pigment network: an additional dermoscopic feature for the diagnosis of melanoma.

BACKGROUND: The negative pigment network (NPN) is seen as a negative of the pigmented network and it is purported to be a melanoma-specific structure. OBJECTIVES: We sought to assess the frequency, sensitivity, specificity, and odds ratios (ORs) of NPN between melanoma cases and a group of control lesions. METHODS: Digitalized images of skin lesions from 679 patients with histopathological diagnosis of dermatofibroma (115), melanocytic nevus (220), Spitz nevus (139), and melanoma (205) were retrospectively collected and blindly evaluated to assess the presence/absence of NPN. RESULTS: The frequency of occurrence of NPN was higher in the melanoma group (34.6%) than in Spitz nevus (28.8%), melanocytic nevus (18.2%), and dermatofibroma (11.3%) groups. An OR of 1.8 emerged for the diagnosis of melanoma in the presence of NPN as compared with nonmelanoma diagnosis. Conversely, for melanocytic nevi and dermatofibromas the OR was very low (0.5 and 0.3, respectively). For Spitz nevi the OR of 1.1 was not statistically significant. When comparing melanoma with dermatofibroma, melanocytic nevus, and Spitz nevus, we observed a significantly higher frequency of multicomponent pattern (68.1%), asymmetric pigmentation (92.9%), irregularly distributed NPN (87.3%), and peripheral location of NPN (66.2%) in melanomas. LIMITATIONS: Further studies can provide the precise dermoscopic-histopathologic correlation of NPN in melanoma and other lesions. CONCLUSIONS: The overall morphologic pattern of NPN, such as the irregular distribution and the peripheral location of NPN, along with the multicomponent pattern and the asymmetric pigmentation could be used as additional features in distinguishing melanoma from Spitz nevus and other benign lesions.

Line-field confocal optical coherence tomography as a tool for three-dimensional in vivo quantification of healthy epidermis: A pilot study.

Epidermal three-dimensional (3D) topography/quantification has not been completely characterized yet. The recently developed line-field confocal optical coherence tomography (LC-OCT) provides real-time, high-resolution, in-vivo 3D imaging of the skin. This pilot study aimed at quantifying epidermal metrics (epidermal thicknesses, dermal-epidermal junction [DEJ] undulation and keratinocyte number/shape/size) using 3D LC-OCT. For each study participant (8 female, skin-type-II, younger/older volunteers), seven body sites were imaged with LC-OCT. Epidermal metrics were calculated by segmentations and measurements assisted by artificial intelligence (AI) when appropriate. Thicknesses of epidermis/SC, DEJ undulation and keratinocyte nuclei volume varied across body sites. Evidence of keratinocyte maturation was observed in vivo: keratinocyte nuclei being small/spherical near the DEJ and flatter/elliptical near the skin surface. Skin microanatomy can be quantified by combining LC-OCT and AI. This technology could be highly relevant to understand aging processes and conditions linked to epidermal disorders. Future clinical/research applications are to be expected in this scenario.

Line field confocal optical coherence tomography: An adjunctive tool in the diagnosis of autoimmune bullous diseases.

Autoimmune bullous diseases (AIBDs) still represent a considerable a source of morbidity and mortality: early identification of a specific AIBD is often difficult due to overlapping clinical and/or laboratory features and time-consuming invasive laboratory tests. We aimed to investigate the potential role of a new imaging technology, line-field confocal optical coherence tomography (LC-OCT), in the non-invasive diagnosis of AIBDs. LC-OCT was performed at lesional, perilesional and contralateral healthy sites in 30 patients, before histology and direct immunofluorescence. LC-OCT examination was able to identify the level of split (subcorneal/suprabasal/subepidermal/sublamina densa), to provide detailed images of the bulla roof morphology and content (eg, erythrocytes/acantholytic cells/polymorphonucleates). Areas of intra/subepidermal detachment were also detected also at clinically normal perilesional skin sites. LC-OCT can support physicians, real time and at bed-site, in the differential diagnosis of various AIBDs and their mimickers. Moreover, it can be used for the identification of subclinical lesions and therapy tapering.

Entodermoscopy: a new tool for diagnosing skin infections and infestations.

BACKGROUND: There is upcoming evidence that dermoscopy facilitates the in vivo diagnosis of skin infections and infestations. As such, dermoscopy connects the research fields of dermatologists and entomologists, opening a new research field of 'entodermoscopy'. OBJECTIVE: To provide an overview on the current applications of entodermoscopy. METHODS: Systematic review of the English- and German-language literature by searches of Medline, Medscape and abstracts of the 1st World Congress of the International Dermoscopy Society. RESULTS: Dermoscopic patterns have been described for viral warts, molluscum contagiosum, scabies, pediculosis, tinea nigra, tungiasis, cutaneous larva migrans, ticks and reactions to spider leg spines. Besides the diagnostic role of dermoscopy, there is increasing evidence that it can also assist in the monitoring of treatment efficacy for some of these conditions. CONCLUSION: Although most of the current available literature is based on single observations and small case studies rather than controlled trials, an increasing interest in this field can be observed.

Biochemotherapy with temozolomide, cisplatin, vinblastine, subcutaneous interleukin-2 and interferon-alpha in patients with metastatic melanoma.

The aim of this study was to determine the efficacy and tolerability of a biochemotherapy regimen, including low-dose subcutaneous interleukin-2 and temozolomide, in patients with metastatic melanoma. Treatment consisted of temozolomide (150 mg/m per day on days 1-5), cisplatin (20 mg/m per day intravenously on days 1-4), vinblastine (1.5 mg/m per day on days 1-4), interleukin-2 (4.5 MU/m per day subcutaneously on days 5-8) and interferon-alpha2b (5 MU subcutaneously on days 5-9, 11, 13, 15, every 28 days). Thirty-six patients were included. Patients with poor prognostic factors were not excluded. Seventeen patients (47%) had been treated previously in an adjuvant setting with interferon-alpha. Four patients (11%) had been treated previously with chemotherapy and six (17%) had been treated with other biochemotherapy regimens. The distribution by American Joint Committee on Cancer staging was as follows: M1a in two patients (6%), M1b in 11 patients (31%) and M1c in 23 patients (64%). At inclusion, seven patients (19.4%) had cerebral metastases that had previously been treated with whole brain radiotherapy. For thirty-four evaluable patients, seven (20.5%) achieved an objective response. Overall, metastatic disease was substantially decreased or temporarily stabilized in 11 patients (32.4%; 95% confidence interval, 17.4-50.5). Responses were observed for all locations. The central nervous system was the initial site of relapse in two responding patients. The median survival was 10 months. The main toxicities noted were haematological (grades 3-4): neutropenia (1.8%), thrombocytopenia (1.8%) and anaemia (1.2%). It can be concluded that this regimen is well tolerated and has a modest activity despite the poor prognosis of our patient population. The low haematological toxicity rate obtained suggests that higher doses could be tried.

Ex vivo dermoscopy for biobank-oriented sampling of melanoma.

IMPORTANCE: In the era of targeted therapy for cancer, translational research identifying molecular targets in melanoma offers novel opportunities for potential new treatments. OBJECTIVES: To describe a method for sampling fresh tissue from primary melanoma and to test whether the area of maximal thickness can be identified with dermoscopy to ensure it remains available for routine histopathological diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Tumors clinically suspicious for melanoma with diameter exceeding 5 mm were included. Dermoscopy-guided sampling was performed using a 2-mm to 3-mm punch through not the thickest part of the tumor. In vivo and ex vivo dermoscopic images obtained were available to the diagnosing pathologist. Melanoma samples were obtained in a referral melanoma unit. MAIN OUTCOMES AND MEASURES: In study 1, Breslow thickness in 10 melanomas was compared between sampled tissue and the remaining specimen to confirm that the area of maximal thickness remained available for the histopathological diagnosis. In study 2, forty-three additional melanomas were sampled for biobanking prospectively. Agreement between 2 independent observers on dermoscopic identification of the thickest part of the melanoma was studied. RESULTS: In study 1, the area of maximal Breslow thickness in all 10 melanomas was not sampled and remained in the main specimen. In study 2, sampling was performed by one of the investigators. Concordance was 93% between 2 independent observers for the dermoscopic selection of the thickest portion of the melanoma. Pathologists asserted that the sampling procedure did not compromise their ability to evaluate melanoma specimens. A limitation is that this is a single-center study. Each case required joint evaluation by expert dermoscopists and dermatopathologists. CONCLUSIONS AND RELEVANCE: In applying the dermoscopy-guided sampling protocol, we make the following 5 recommendations: Samples should only be obtained from areas that will not interfere with the pathologist's diagnosis and prognostic information. Sampling should not be obtained from tumors for which one suspects that the histopathological evaluation may prove difficult. Sampling should not be performed on small melanomas; we recommend a minimum diameter of 10 mm. All the dermoscopy-guided sampling should be documented with images, available to pathologists and clinicians, and reflected in the pathology report. Finally, the frozen biobank samples should be made available for routine hematoxylin-eosin histopathological evaluation until the final pathology report is produced. Ex vivo dermoscopy may serve to guide the procurement of small samples from primary melanoma for fresh tissue biobanking without compromising the histopathological evaluation.

Evidence of a limited intra-individual diversity of nevi: intuitive perception of dominant clusters is a crucial step in the analysis of nevi by dermatologists.

Although nevi are highly polymorphous, it has been suggested that each individual is characterized by only a few dominant patterns of nevi. Therefore, a nevus that does not fit in with these patterns, the "ugly duckling" nevus, is suspicious. Our objective was to study the intra-individual diversity of nevi, using human ability to build "perceived similarity clusters" (PSCs). Nine dermatologists had to cluster all the nevi of 80 patients into PSCs, at the clinical scale (CS) and at the dermoscopic scale (DS) (subset of 30 patients). Nine novices did the same in a subset of 11 patients. The experts identified a mean of 2.8 PSCs/patient at CS. Concordance was higher between experts than between novices at CS and at DS. Despite a trend for more PSCs at DS than at CS, the number of nevus patterns per patient remained low, regardless of the number of nevi. Inter-expert concordance permits a consensus representation of nevus diversity in each individual. Nevus diversity is limited in each patient and constitutes an individual reference system, which we can intuitively perceive. This reference is probably crucial for nevus analysis and melanoma detection and opens perspectives for computer-aided diagnostics.