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This article is a systematic review of studies that explore the use of game-based learning (GBL) in dermatology education. The review found that GBL can be an effective approach to teaching dermatology, with positive attitudes and favorable learning outcomes reported. However, the study quality of the reviewed articles was generally low, and there is a need for high-quality studies with objective outcomes. The authors suggest that GBL could play an important role in future dermatology training, but more research is needed to support its effectiveness. The study was funded by the Copenhagen Capital Region Postdoctorate Research Fund and the authors declare no conflicts of interest. [Extracted from the article]

Background: Line‐field confocal optical coherence tomography (LC‐OCT) is an emerging diagnostic tool with imaging depth reaching ~400 μm and a novel three‐dimensional (3D) cube providing cellular resolution. As far as we are aware, there are only a limited number of papers that have reported diagnostic criteria for melanocytic lesions using this technique, and none of them have been multicentric. Objectives: Our aim was to establish the diagnostic criteria for melanocytic lesions using LC‐OCT and identify the most significant architectural and cytologic features associated with malignancy. Methods: A retrospective evaluation of 80 consecutive melanocytic lesions from a prospective multicentric data set spanning three European centres was conducted. We excluded facial, acral and mucosal lesions from the study. Dermoscopic and LC‐OCT images were evaluated by a consensus of four observers. Multivariate logistic regression with backward elimination was employed. Results: The main melanoma diagnostic criteria include detecting >10 pagetoid cells in 3D acquisition, irregular 3D epidermal architecture, disrupted dermoepidermal junction (DEJ) and clefting. Significant risk factors were irregular 3D epidermal architecture, >10 pagetoid cells, dendritic cells at DEJ without underlying inflammation. Novel malignancy criteria in vertical view were DEJ disruption and clefting around atypical melanocyte nests. Exclusive melanoma features were epidermal nests, epidermal consumption, dense dermal nests with atypia. Protective features in the absence of any malignancy indicators were DEJ ring pattern, cobblestone, elongated rete ridges (vertical), well‐defined DEJ and wave pattern (vertical). Conclusions: A series of diagnostic criteria for the identification of melanocytic lesions with LC‐OCT have been established. Validation of these criteria in clinical practice through future studies is essential to further establish their utility. [ABSTRACT FROM AUTHOR]

Background: Early melanoma detection is the main factor affecting prognosis and survival. For that reason, non‐invasive technologies have been developed to provide a more accurate diagnosis. Recently, line‐field confocal optical coherence tomography (LC‐OCT) was developed to provide an in vivo, imaging device, with deep penetration and cellular resolution in three dimensions. Combining the advantages of conventional OCT and reflectance confocal microscopy, this tool seems to be particularly suitable for melanocytic lesions. Objectives: The objective of this study was to identify and describe the correlation between specific dermoscopic criteria and LC‐OCT features in three dimensions associated with melanocytic lesions. Methods: Dermoscopic and LC‐OCT images of 126 melanocytic lesions were acquired in three different centres. The following dermoscopic criteria have been considered: reticular pattern, dots and globules, structureless areas, blue‐whitish veil, regression structures, negative network, homogeneous pattern, streaks and blotches. Results: 69 (55%) benign and 57 (45%) malignant lesions were analysed. A regular reticular pattern was found associated in the 75% of the cases with the presence of elongated rete ridges with pigmented cells along the basal layer, while atypical reticular pattern showed an irregular organization of rete ridges with melanocytic hyperplasia, broadened and fused ridges and elongated nests. Both typical and atypical dots and globules were found associated with melanocytic nests in the dermis or at the dermoepidermal junction (DEJ), as well as with keratin cysts/pseudocysts. Grey globules corresponded to the presence of melanin‐containing dermal inflammatory cells (melanophages) within the papillae. Structureless brown/black areas correlated with alterations of the DEJ. We observed the same DEJ alterations, but with the presence of dermal melanophages, in 36% of the cases of blue/white/grey structureless areas. A description of each LC‐OCT/dermoscopy correlation was made. Conclusions: LC‐OCT permitted for the first time to perform an in vivo, 3D correlation between dermoscopic criteria and pathological‐like features of melanocytic lesions. [ABSTRACT FROM AUTHOR]

Background: In vivo reflectance confocal microscopy (RCM) enables the study of architectural and cytological aspects in horizontal sections, which closely correlate with histologic features. However, traditional histopathological vertical sections cannot totally reproduce the image of the in vivo RCM horizontal section. Objective: To evaluate the concordance between in vivo RCM and histopathologic transverse sections for melanocytic lesions, basal cell carcinoma and seborrheic keratoses. Methods: Prospectively collected benign melanocytic and non‐melanocytic tumours diagnosed by dermoscopy were evaluated for common RCM features and compared to histopathology in horizontal sections with haematoxylin and eosin staining. Results: A total of 44 skin tumours including 19 melanocytic lesions (nine compound, five junctional and five intradermal nevi), 12 basal cell carcinomas and 13 seborrheic keratoses were collected in the Department of Dermatology of Hospital Clinic of Barcelona. The RCM features that had statistically significant agreement with the histopathological horizontal sections were the preserved and visible honeycomb pattern, well defined DEJ, small bright particles, dermal nests, tumour islands and dark silhouettes, clefting, collagen bundles, thickened collagen bundles and cytologic atypia. Conclusions: Histopathology evaluation of horizontal sections of skin tumours can be correlated with main RCM findings. The results of this study have improved the understanding and interpretation of RCM features in relation to skin tumours, thus reinforcing the utility of RCM as a diagnostic tool. [ABSTRACT FROM AUTHOR]

Background: Most of large epidemiological studies on melanoma susceptibility have been conducted on fair skinned individuals (US, Australia and Northern Europe), while Southern European populations, characterized by high UV exposure and dark‐skinned individuals, are underrepresented. Objectives: We report a comprehensive pooled analysis of established high‐ and intermediate‐penetrance genetic variants and clinical characteristics of Mediterranean melanoma families from the MelaNostrum Consortium. Methods: Pooled epidemiological, clinical and genetic (CDKN2A, CDK4, ACD, BAP1, POT1, TERT, and TERF2IP and MC1R genes) retrospective data of melanoma families, collected within the MelaNostrum Consortium in Greece, Italy and Spain, were analysed. Univariate methods and multivariate logistic regression models were used to evaluate the association of variants with characteristics of families and of affected and unaffected family members. Subgroup analysis was performed for each country. Results: We included 839 families (1365 affected members and 2123 unaffected individuals). Pathogenic/likely pathogenic CDKN2A variants were identified in 13.8% of families. The strongest predictors of melanoma were ≥2 multiple primary melanoma cases (OR 8.1; 95% CI 3.3–19.7), >3 affected members (OR 2.6; 95% CI 1.3–5.2) and occurrence of pancreatic cancer (OR 4.8; 95% CI 2.4–9.4) in the family (AUC 0.76, 95% CI 0.71–0.82). We observed low frequency variants in POT1 (3.8%), TERF2IP (2.5%), ACD (0.8%) and BAP1 (0.3%). MC1R common variants (≥2 variants and ≥2 RHC variants) were associated with melanoma risk (OR 1.4; 95% CI 1.0–2.0 and OR 4.3; 95% CI 1.2–14.6, respectively). Conclusions: Variants in known high‐penetrance genes explain nearly 20% of melanoma familial aggregation in Mediterranean areas. CDKN2A melanoma predictors were identified with potential clinical relevance for cancer risk assessment. [ABSTRACT FROM AUTHOR]

This article discusses the use of line-field confocal optical coherence tomography (LC-OCT) as a new tool for assessing cutaneous mycosis fungoides (MF), the most common variant of cutaneous T-cell lymphoma. The early diagnosis of MF is challenging and often results in a therapeutic delay. LC-OCT allows for the visualization of various features of MF, such as epidermal architectural disarray, atypical lymphocytes, and dermal changes. The study demonstrates that LC-OCT has a high correlation with histology and can provide valuable information for the diagnosis and follow-up of MF. [Extracted from the article]

Background: Around 0.5% of cutaneous melanoma (CM) patients will present with synchronous melanomas when first seen. Moreover, 26–40% of patients with multiple primary melanomas present with synchronous lesions. Objectives: To assess the prevalence, clinical and histopathological characteristics, germline mutations and outcome in patients with synchronous melanoma. Methods: Clinical and histopathological data from 4703 melanoma patients were included. Clinical, histological and genetic mutational status information was analysed. Kaplan–Meier curves were used to investigate survival outcomes. Results: A total of 144 patients (3.06%) presented simultaneously with two or more primary melanomas. During follow‐up, 25.7% of patients with synchronous melanoma developed a new primary melanoma compared to 8.6% of patients diagnosed with single melanoma (P < 0.001). Germinal CDKN2A mutations were identified in 10.7% of patients with synchronous melanomas and genetic variants in MC1R in 72%. No significant differences in all survival outcomes between patients with synchronous melanomas and single melanomas were found. Conclusion: Synchronous melanomas are more frequent than previously reported and are more frequent in older patients compared to single melanomas. Moreover, these patients have a higher risk of developing a new primary melanoma during follow‐up and have higher rates of germline susceptibility variants. Nevertheless, these findings were not associated with worse outcomes. [ABSTRACT FROM AUTHOR]

Background: Basosquamous carcinoma (BSC) is a rare and potentially aggressive cutaneous neoplasm combining histopathological features of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Line‐field confocal optical coherence tomography (LC‐OCT) is a new, non‐invasive imaging technique featuring excellent resolution and penetration. To date, studies about the use of LC‐OCT in the BCC and SCC fields are available, but similar investigations are lacking in the BSC field. Objective: The goal of the present study was to identify/describe LC‐OCT criteria of BSC. Methods: Consecutively enrolled BSCs were imaged with dermoscopy and LC‐OCT prior to surgical excision. Dermoscopic and LC‐OCT images were evaluated, and histopathological slides were reviewed. Results: Six BSCs from six patients [four (66.7%) males and two (33.3%) females; mean age 76.5 (62–96) years] were included. Identified LC‐OCT criteria for BSC included BCC‐associated (dermal lobules with millefeuille pattern, dilated vessels, bright cells within the epidermis, bright cells within lobules, stromal stretching, stromal brightness) and SCC‐associated features (acanthosis, hyperkeratosis, disarranged epidermal architecture, broad strands, elastosis and glomerular vessels). Interruption of the dermal–epidermal junction and ulceration represented overlapping criteria. Conclusion: Line‐field confocal‐OCT is a new promising technique that may support the non‐invasive recognition of BSC through the simultaneous detection of BCC‐associated and SCC‐associated features. We hypothesize that the use of LC‐OCT might be helpful not only in the diagnostic setting but also in the follow‐up surveillance for an early identification of recurrences. Further larger studies are needed to prove this hypothesis. [ABSTRACT FROM AUTHOR]

Medical device (MD) is a broad term that encompasses products ranging from, for example, examination gloves to digital dermoscopy systems; all of which are regulated by a new regulatory framework in the EU from May 2021. The new Medical Device Regulation (MDR) (Regulation EU 2017/745) will have a significant effect on suppliers of MD and will have subsequent effects also for dermatologists and other clinicians. Medical device software and apps are reclassified leading to more stringent requirements on documentation within, e.g. clinical evidence, as well as regulatory authority control. The changes will likely have positive effects on quality, to the benefit of patients. There will, however, be implications affecting the availability and support of existing devices and the introduction of new devices, as well as a likely price increase due to the higher costs for suppliers. Dermatologists, other clinicians and administrators need to be aware of the effects of MDR to ensure that existing devices and new purchases can be used as planned. Specifically, clinicians need to be aware of the following: (i) improved quality of MD and follow‐up of incidents can be expected. (ii) Only 'non‐significant' updates will be permitted after May 2021 to many existing systems and devices unless approved under the new MDR. (iii) Existing devices that do not achieve approval under the new regulation will no longer be manufactured after May 2024. (iv) New products and methods will take longer time to be approved and available. (v) Prices will likely increase. (vi) Suppliers of products that do not fulfil the new regulation will disappear, and the availability of consumables, spare parts or upgrades might be discontinued. (vii) A trend to oligopoly may appear in the market. It is therefore important to check with your suppliers as to how and when they will adhere to the new MDR regulation. [ABSTRACT FROM AUTHOR]

Background: No simple staging system has emerged for basal cell carcinomas (BCCs), since they do not follow the TNM process, and practitioners failed to agree on simple clinical or pathological criteria as a basis for a classification. Operational classification of BCCs is required for decision‐making, trials and guidelines. Unsupervised clustering of real cases of difficult‐to‐treat BCCs (DTT‐BCCs; part 1) has demonstrated that experts could blindly agree on a five groups classification of DTT‐BCCs based on five patterns of clinical situations. Objective: Using this five patterns to generate an operational and comprehensive classification of BCCs. Method: Testing practitioner's agreement, when using the five patterns classification to ensure that it is robust enough to be used in the practice. Generating the first version of a staging system of BCCs based on pattern recognition. Results: Sixty‐two physicians, including 48 practitioners and the 14 experts who participated in the generation of the five different patterns of DTT‐BCCs, agreed on 90% of cases when classifying 199 DTT‐BCCs cases using the five patterns classification (part 1) attesting that this classification is understandable and usable in practice. In order to cover the whole field of BCCs, these five groups of DTT‐BCCs were added a group representing the huge number of easy‐to‐treat BCCs, for which sub‐classification has little interest, and a group of very rare metastatic cases, resulting in a four‐stage and seven‐substage staging system of BCCs. Conclusion: A practical classification adapted to the specificities of BCCs is proposed. It is the first tumour classification based on pattern recognition of clinical situations, which proves to be consistent and usable. This EADO staging system version 1 will be improved step by step and tested as a decision tool and a prognostic instrument. [ABSTRACT FROM AUTHOR]

Dermatoscopic features of thin (<=2 mm Breslow thickness) vs. thick (>2 mm Breslow thickness) nodular melanoma and predictors of nodular melanoma versus nodular non-melanoma tumours: a multicentric collaborative study by the International Dermoscopy Society. GLO:3NZ/01nov21:jdv17428-fig-0001.jpg PHOTO (COLOR): 1 Nodular melanomas presenting with a typical clinical morphology as arises from an agreement of 4 out of 6 evaluators: (a) pigmented nodular melanoma-like, (b) hypo/amelanotic melanoma-like and nodular melanomas imitating benign and malignant non-melanoma lesions, (c) seborrheic keratosis-like, (d) pyogenic granuloma-angioma-angiokeratoma-like and (e)-(f) non-melanoma skin cancer-like. gl The distinct patterns of NM identified are of great importance to address the early detection of this melanoma subtype in clinical practice. Dermoscopy improves the diagnostic accuracy of melanomas clinically resembling seborrheic keratosis: cross-sectional study of the ability to detect seborrheic keratosis-like melanomas by a group of dermatologists with varying degrees of experience. [Extracted from the article]

Background: No simple classification system has emerged for 'advanced basal cell carcinomas', and more generally for all difficult‐to‐treat BCCs (DTT‐BCCs), due to the heterogeneity of situations, TNM inappropriateness to BCCs, and different approaches of different specialists. Objective: To generate an operational classification, using the unconscious ability of experts to simplify the great heterogeneity of the clinical situations into a few relevant groups, which drive their treatment decisions. Method: Non‐supervised independent and blinded clustering of real clinical cases of DTT‐BCCs was used. Fourteen international experts from different specialties independently partitioned 199 patient cases considered 'difficult to treat' into as many clusters they want (≤10), choosing their own criteria for partitioning. Convergences and divergences between the individual partitions were analyzed using the similarity matrix, K‐mean approach, and average silhouette method. Results: There was a rather consensual clustering of cases, regardless of the specialty and nationality of the experts. Mathematical analysis showed that consensus between experts was best represented by a partition of DTT‐BCCs into five clusters, easily recognized a posteriori as five clear‐cut patterns of clinical situations. The concept of 'locally advanced' did not appear consistent between experts. Conclusion: Although convergence between experts was not granted, this experiment shows that clinicians dealing with BCCs all tend to work by a similar pattern recognition based on the overall analysis of the situation. This study thus provides the first consensual classification of DTT‐BCCs. This experimental approach using mathematical analysis of independent and blinded clustering of cases by experts can probably be applied to many other situations in dermatology and oncology. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis and subtype classification of basal cell carcinoma (BCC) are crucial to reduce morbidity and optimize treatment. Good accuracy in differentiating BCC from clinical imitators has been achieved with existing diagnostic strategies but lower performance in discriminating BCC subtypes. Line‐field confocal optical coherence tomography (LC‐OCT) is a new technology able to combine the technical advantages of reflectance confocal microscopy and OCT. Objectives: To identify and describe LC‐OCT criteria associated with BCC and explore their association with BCC subtypes. Methods: Basal cell carcinoma were imaged with a handheld LC‐OCT device before surgical excision. LC‐OCT images were retrospectively evaluated by three observers for presence/absence of criteria for BCC. Multivariate logistic regression models were used to find independent predictors of BCC subtypes. Results: Eighty‐nine histopathologically proven BCCs were included, of which 66 (74.2%) were pure subtypes [superficial BCC (sBCC): 19/66 (28.8%); nodular BCC (nBCC): 31/66 (47.0%); infiltrative BCC (iBCC): 16/66 (24.2%)]. Lobules, blood vessels and small bright cells within epidermis/lobules were the most frequent criteria for BCC. LC‐OCT criteria independently associated with sBCC were presence of hemispheric lobules, absence of lobule separation from the epidermis, absence of stretching of the stroma; with nBCC were presence of macrolobules, absence of lobule connection to the epidermis; and with iBCC were presence of branched lobules. Conclusions: This was the first study describing the characteristics of BCC under LC‐OCT examination. We proposed morphologic criteria, which could be potentially useful for diagnosis and subtype classification of BCC, as well as for its therapeutic management. Future studies are needed to assess these hypotheses. [ABSTRACT FROM AUTHOR]

Background: MC1R polymorphisms interact with CDKN2A mutations modulating melanoma risk and contribute to a less suspicious clinical and dermoscopic appearance of melanomas. Different strategies, including dermoscopic comparative approach and digital monitoring, are used for the melanoma diagnosis in this context. Objective: To analyse the diagnostic accuracy of the morphologic approach and comparative approach in dermoscopy, and to detect melanoma in familial melanoma (FamMM) patients according to different genetic backgrounds. Methods: Two independent readers evaluated 415 lesions belonging to 25 FamMM: 26 melanomas (62% in situ, 36% early invasive) and 389 naevi, blinded for dermoscopic and histopathologic diagnosis, following two different steps. First step‐Randomized: all lesions were randomly located in one single folder. Second step‐Comparative approach: the lesions were clustered by patient. Sensitivity, specificity and number needed to excise (NNE) for melanoma diagnosis were calculated for both diagnostic strategies. Sensitivity and specificity were also assessed regarding the genetic background. Results: The comparative approach showed lower sensitivity compared to the morphologic approach (69.2 and 73.1 vs. 76.9 both readers) but better specificity (95.9 and 95.1 vs. 84.3 and 90.2, respectively). NNE was better in the comparative approach. The readers had more difficulties diagnosing lesions from CDKN2A mutation carriers with red hair colour (RHC) MC1R variants. Conclusion: The comparative approach can be useful in high‐risk patients to decrease the NNE. Early melanomas in CDKN2A carriers with RHC polymorphisms are more difficult to diagnose even with the comparative approach and benefit from the detection of changes during digital dermoscopy monitoring for early diagnosis. Linked Commentary: A. Lallas. J Eur Acad Dermatol Venereol 2021; 35: 274‐275. https://doi.org/10.1111/jdv.17104. [ABSTRACT FROM AUTHOR]

Background: Treatment response for psoriasis is typically evaluated using clinical scores. However, patients can relapse after clinical clearance, suggesting persistent inflammation. Dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) can non‐invasively improve treatment response assessment. Objectives: To compare the clinical and non‐invasive microscopic features in a psoriatic target lesion treated with clobetasol cream or calcipotriol/betamethasone dipropionate foam (Cal/BD foam). Methods: Prospective, unicentric, open, randomized clinical trial comparing clinical data [total clinical score (TCS)] and microscopic data (dermoscopy, RCM and OCT) in psoriasis patients treated with clobetasol or Cal/BD foam. Results: We included 36 adult patients (22 men). At week 4, more patients treated with Cal/BD foam achieved TCS ≤1 than with clobetasol (63.2% vs. 18.8%, P = 0.016). Treatment satisfaction was higher with Cal/BD foam (P < 0.03). Microscopically, Cal/BD foam induced more reduction in epidermal thickness at week 4 (P < 0.049). Dilated horizontal blood vessels were more common with clobetasol than with Cal/BD foam at week 8 (69.2% vs. 31.2%, P = 0.159). If epidermal hyperplasia was noted at baseline, the response was poorer with clobetasol (P = 0.029). Limitations: Small sample size, open study, imaging sampling bias. Conclusion: Cal/BD foam is more effective than clobetasol, has better patient satisfaction and induces greater reduction in the hyperkeratosis/acanthosis, regardless of baseline epidermal hyperplasia. [ABSTRACT FROM AUTHOR]

Background: Line‐field confocal optical coherence tomography (LC‐OCT) is a non‐invasive optical technique recently developed for skin examination in vivo. It provides real‐time, high‐resolution vertical images with an isotropic resolution of ~1 µm and a penetration depth of ~500 µm. Objectives: Study goals were to qualitatively/quantitatively characterize healthy skin at different body sites using LC‐OCT. Methods: The skin of young healthy volunteers was imaged with a handheld LC‐OCT imaging device. Seven body sites (back of the hand, forehead, cheek, nose, chest, forearm and back) were investigated. An independent qualitative [cutaneous structures' description; visibility of keratinocytes' nuclei and dermal–epidermal junction (DEJ)] and quantitative [stratum corneum (SC)/epidermal thicknesses; height of dermal papillae] assessment of the LC‐OCT images was performed. Results: A total of 88 LC‐OCT images were collected from 29 participants (20 females; nine males; mean age 25.9 years). Keratinocytes' nuclei and DEJ were visible in the totality of images. The different layers of the epidermis and the remaining cutaneous structures/findings were visualized. Body sites‐related variability was detected for SC/epidermal thicknesses and height of dermal papillae. Inter‐observer agreement was excellent (SC thickness), good‐to‐excellent (epidermal thickness) and moderate‐to‐good (papillae). Conclusions: Line‐field confocal‐OCT provides non‐invasive, real‐time imaging of the skin in vivo with deep penetration and high resolution, enabling the visualization of single cells. The histology‐like vertical view provides an easy way to recognize/measure different cutaneous structures/findings. LC‐OCT appears as a promising technique for the examination of physiological/pathological skin. [ABSTRACT FROM AUTHOR]

Background: There is no internationally vetted set of anatomic terms to describe human surface anatomy. Objective: To establish expert consensus on a standardized set of terms that describe clinically relevant human surface anatomy. Methods: We conducted a Delphi consensus on surface anatomy terminology between July 2017 and July 2019. The initial survey included 385 anatomic terms, organized in seven levels of hierarchy. If agreement exceeded the 75% established threshold, the term was considered 'accepted' and included in the final list. Terms added by the participants were passed on to the next round of consensus. Terms with <75% agreement were included in subsequent surveys along with alternative terms proposed by participants until agreement was reached on all terms. Results: The Delphi included 21 participants. We found consensus (≥75% agreement) on 361/385 (93.8%) terms and eliminated one term in the first round. Of 49 new terms suggested by participants, 45 were added via consensus. To adjust for a recently published International Classification of Diseases‐Surface Topography list of terms, a third survey including 111 discrepant terms was sent to participants. Finally, a total of 513 terms reached agreement via the Delphi method. Conclusions: We have established a set of 513 clinically relevant terms for denoting human surface anatomy, towards the use of standardized terminology in dermatologic documentation. Linked Commentary: R.J.G. Chalmers. J Eur Acad Dermatol Venereol 2020; 34: 2456–2457. https://doi.org/10.1111/jdv.16978. [ABSTRACT FROM AUTHOR]

Background: Thin nodular melanoma (NM) often lacks conspicuous melanoma‐specific dermatoscopic criteria and escapes clinical detection until it progresses to a thicker and more advanced tumour. Objective: To investigate the dermatoscopic morphology of thin (≤2 mm Breslow thickness) vs. thick (>2 mm) NM and to identify dermatoscopic predictors of its differential diagnosis from other nodular tumours. Methods: Retrospective, morphological case–control study, conducted on behalf of the International Dermoscopy Society. Dermatoscopic images of NM and other nodular tumours from 19 skin cancer centres worldwide were collected and analysed. Results: Overall, 254 tumours were collected (69 NM of Breslow thickness ≤2 mm, 96 NM >2 mm and 89 non‐melanoma nodular lesions). Light brown coloration (50.7%) and irregular brown dots/globules (42.0%) were most frequently observed in ≤2 mm NMs. Multivariate analysis revealed that dotted vessels (3.4‐fold), white shiny streaks (2.9‐fold) and irregular blue structureless area (2.4‐fold) were predictors for thinner NM compared to non‐melanoma nodular tumours. Overall, irregular blue structureless area (3.4‐fold), dotted vessels (4.6‐fold) and serpentine vessels (1.9‐fold) were predictors of all NM compared to non‐melanoma nodular lesions. Limitations: Absence of a centralized, consensus pathology review and cases selected form tertiary centres maybe not reflecting the broader community. Conclusions: Our study sheds light into the dermatoscopic morphology of thin NM in comparison to thicker NM and could provide useful clues for its differential diagnosis from other non‐melanoma nodular tumours. [ABSTRACT FROM AUTHOR]

These technical characteristics make the LC-OCT a valuable tool for the examination of physiological skin2 as well as for the diagnosis of different types of skin lesions.3-9 Actinic keratosis (AK) is the most common precancerous cutaneous lesion and is mainly observed on chronically sun-exposed skin. GLO:3NZ/01dec21:jdv17548-fig-0002.jpg PHOTO (COLOR): 2 LC-OCT and histopathological presentation of four different subtypes of actinic keratoses (AKs): atrophic AK on the right temple of a 77-year-old woman (a, b); hypertrophic AK on the left leg of a 55-year-old man (c, d); proliferative AK on the left breast of a 71-year-old man (e, f); and acantholytic AK on the nose dorsum of a 77-year-old woman (g, h). GLO:3NZ/01dec21:jdv17548-fig-0001.jpg PHOTO (COLOR): 1 Actinic keratosis (AK) on the right upper-lip of a 74-year-old woman: clinical (a), dermoscopic (b), line-field confocal optical coherence tomography (LC-OCT) (c) and histopathological (d) presentation; squamous cell carcinoma (SCC) on the left cheek of an 82-year-old man: clinical (e), dermoscopic (f), LC-OCT (g) and histopathological (h) presentation. [Extracted from the article]

In order to study this, we retrospectively reviewed confocal findings of 20 cases of inflamed tumours: 5 thin melanomas with regression features on histopathology, 5 banal naevi and 10 histologically proven Sutton's naevi. In conclusion, marked inflamed naevi such as Sutton's naevi can simulate melanoma when assessed by RCM and vice versa: they could be a pitfall in RCM evaluation even in the hands of confocal experts. [Extracted from the article]

Sonidegib and vismodegib are hedgehog pathway inhibitors (HhIs) approved for the treatment of advanced basal cell carcinoma (BCC). Until recently, vismodegib was the only targeted treatment available for patients with locally advanced BCC (laBCC) in cases where surgery and radiotherapy are inappropriate. Sonidegib has recently been approved and now presents an alternative treatment option. The clinical differences between the two HhIs in patients with laBCC are unclear, as no head‐to‐head randomized controlled trials are or will be initiated. Moreover, there were important differences in the designs of their pivotal studies, BOLT (sonidegib) and ERIVANCE (vismodegib), and these differences complicate evidence‐based analysis of their relative efficacy and safety profiles. In this paper, a group of clinical experts in the management of laBCC summarizes the clinical and pharmacological profiles of sonidegib and vismodegib based on published data and their own clinical experience. One key difference between the two pivotal studies was the criteria used to assess BCC severity. ERIVANCE (a single‐arm phase II trial) used the conventional Response Evaluation Criteria in Solid Tumors (RECIST), while the more recent double‐blind randomized BOLT trial used the stringent modified RECIST. A preplanned analysis adjusted the outcomes from BOLT with RECIST‐like criteria, and this enabled the experts to discuss relative efficacy outcomes for the two treatments. Centrally reviewed objective response rate (ORR) for vismodegib was 47.6% (95% CI: 35.5–60.6) at 21‐month follow‐up using RECIST. After adjusting with RECIST‐like criteria, the ORR for sonidegib according to central review at 18‐month follow‐up was 60.6% (95% CI: 47.8–72.4). Both treatments were associated with similar patterns of adverse events. Sonidegib and vismodegib share the same efficacy and tolerability profiles, but their pharmacokinetic profiles show several differences, such as volume of distribution and half‐life. Further studies are needed to understand how these differences may impact clinical practice. [ABSTRACT FROM AUTHOR]

Background: The role of S100B protein in detecting early melanoma relapses is controversial, since most metastasis occur within normal values of S100B. Objective: The aim of this study was to assess the performance of S100B in detecting early disease progression in high‐risk melanoma patients. Methods: Retrospective cohort study including patients with an initial diagnosis of stage IIB, IIC and III melanoma between January 2003 and July 2013. All patients were followed up in accordance with an intensive protocol based on imaging studies and serum S100B levels every 3–6 months. We compared two methods to evaluate changes in S100B. The classic method referring to a single determination of S100B above the cut‐off level at the time of metastasis, which was evaluated in all patients. And a new method based on monthly changes of S100, which was used in the setting of patients with S100B levels within the normal range. Results: Overall, 289 of patients were followed up for 44 months (IQR 17–73) and 45% developed metastases. During the study period, 129 patients relapsed of which 46 (35.7%) present elevated values of S100B at the time of relapse. The classic method had a sensitivity and specificity of S100B protein of 35.7% and 92.5%, respectively. Furthermore, for the patients that relapsed with normal values of S100B, the new method was applied and showed a sensitivity and specificity of 41.1% and 92.4%, respectively, allowing to detect additional relapses that were missing by the classic method. Conclusion: During follow‐up of high‐risk melanoma patients, rising serum S100B values within the normal range can be an important clue to disease progression. Linked Commentary: C. Posch. J Eur Acad Dermatol Venereol 2020; 34: 1386–1386. https://doi.org/10.1111/jdv.16731. [ABSTRACT FROM AUTHOR]

Background: Mammary Paget's disease (MPD) is a rare intraepidermal adenocarcinoma of the nipple‐areola complex, associated with an underlying breast cancer in approximately 90% of cases. Delayed diagnosis of MPD is common. Its dermoscopic features have been ill defined in the literature. Objectives: To determine the clinical and dermoscopic features of MPD versus other dermatologic entities that involve nipple and areola. Methods: Members of the IDS were invited to submit any case of histologically confirmed MPD, as well as other benign and malignant dermatoses that involve the nipple and areola complex. A standardized evaluation of the dermoscopic images was performed and the results were statistically analyzed. Results: Sixty‐five lesions were included in the study, 22 (33.8%) of them MPD and 43 (66.2%) controls. The most frequent dermoscopic criteria of MPD were white scales (86.4%) and pink structureless areas (81.8%), followed by dotted vessels (72.7%), erosion/ulceration (68.2%) and white shiny lines (63.6%). The multivariate analysis showed that white scales and pink structureless areas were significant predictors of MPD, posing a 68‐fold and a 31‐fold probability of MPD, respectively. Split of the population into pigmented and non‐pigmented lesions showed that in pigmented MPD, pink structureless areas, white lines and grey granules and dots are positive predictors of the disease. Among non‐pigmented lesions, pink structureless areas, white lines, erosion/ulceration and white scales served as predictors of MPD. Conclusions: The most frequent profile of an individual with MPD is an elderly female with unilateral, asymptomatic, erythematous plaque of the nipple, dermoscopically displaying pink structureless areas, fine white scales, dotted and a few short linear vessels. In case of pigmentation we may also observe brown structureless areas and pigmented granules. Limitations: Small sample size, retrospective design. [ABSTRACT FROM AUTHOR]

Absence of large, pleomorphic, hyper-reflective cells in the epidermis and the lobules, which would suggest nests of atypical melanocytic cells. Line-field confocal optical coherence tomography (LC-OCT) is a newly developed non-invasive imaging technique that combines high penetration depth (500 µm, similar to conventional OCT) with high isotropic resolution (lateral 1.3 µm, axial 1.1 µm, similar to reflectance confocal microscopy [RCM]).1 Moreover, with its ability to produce images in both vertical and horizontal planes, it enables a tridimensional (3D) analysis of the skin, which can prove very useful for assessing physiological2 and pathological skin.3-5Sebaceous hyperplasia (SH) is one of the most common lesions that dermatologists can encounter especially on the face of middle-aged to elderly patients. In dermal nevus, a wave-like pattern can be visualized as ill-defined lobules/strands in the dermis corresponding to melanocytic nests (i). gl Previous attempts to define specific criteria in order to recognize SH upon older non-invasive imaging techniques were too often unreliable in daily practice due to technical limitations. [Extracted from the article]

Upon LC-OCT examination, dermal nevi are characterized by the presence in the papillary and reticular dermis of alternating undulated hyper-reflective and hypo-reflective lines corresponding to melanocytic strands/cords/nests in the dermis. We hereby report the main LC-OCT features of dermal nevi and of the dermal component of compound nevi, which we observed in seven histopathologically confirmed cases. Line-field confocal optical coherence tomography (LC-OCT) is a recently developed non-invasive imaging technique able to combine the technical principles of conventional OCT (high in-tissue penetration and visualization of the vertical plane) and reflectance confocal microscopy (high resolution).1-3 Indeed, LC-OCT provides tridimensional images of the skin (vertical and horizontal planes) up to a 500-µm depth and features excellent isotropic resolution (lateral: 1.3 µm; axial: 1.1 µm). [Extracted from the article]

Background: The clinical and pathological features of primary melanoma are not sufficiently sensitive to accurately predict which patients are at a greater risk of relapse. Recently, a 31‐gene expression profile (DecisionDx‐Melanoma) test has shown promising results. Objectives: To evaluate the early prognostic performance of a genetic signature in a multicentre prospectively evaluated cohort. Methods: Inclusion of patients with AJCC stages IB and II conducted between April 2015 and December 2016. All patients were followed up prospectively to assess their risk of relapse. Prognostic performance of this test was evaluated individually and later combined with the AJCC staging system. Prognostic accuracy of disease‐free survival was determined using Kaplan–Meier curves and Cox regression analysis. Results of the gene expression profile test were designated as Class 1 (low risk) and Class 2 (high risk). Results: Median follow‐up time was 26 months (IQR 22–30). The gene expression profile test was performed with 86 patients; seven had developed metastasis (8.1%) and all of them were in the Class 2 group, representing 21.2% of this group. Gene expression profile was an independent prognostic factor for relapse as indicated by multivariate Cox regression analysis, adjusted for AJCC stages and age. Conclusions: This prospective multicentre cohort study, performed in a Spanish Caucasian cohort, shows that this 31‐gene expression profile test could correctly identify patients at early AJCC stages who are at greater risk of relapse. We believe that gene expression profile in combination with the AJCC staging system could well improve the detection of patients who need intensive surveillance and optimize follow‐up strategies. [ABSTRACT FROM AUTHOR]

Background: Vulvar melanosis can occasionally be clinically challenging by mimicking an early melanoma. Objective: To report our experience of initial evaluation and follow‐up in this peculiar subset of vulvar melanosis using reflectance confocal microscopy (RCM). Methods: We retrospectively evaluated 18 consecutive cases referred for atypical vulvar pigmentation or for which melanoma was considered and that underwent both RCM examination and histopathological assessment. In 13 cases with available dermoscopic pictures, RCM classification was compared to dermoscopic diagnosis, and in all cases, the density of melanocytes was evaluated on biopsies using MelanA immunostaining. Results: Among the 18 atypical pigmented lesions, 17 vulvar melanosis and one melanoma were histologically determined. RCM concluded a benign vulvar melanosis in 10 of 17 cases, whereas dermoscopy did so in three of 12 cases. RCM identified the only early malignant lentiginous melanoma. In several cases of vulvar melanosis, RCM could identify foci of melanocytic hyperplasia in an otherwise benign pattern. Conclusions: In this clinically and dermoscopically challenging subset of vulvar pigmentations, RCM appears relevant for initial extensive evaluation, especially to target initial biopsy sampling, and to perform non‐invasive monitoring of foci of melanocytic hyperplasia. [ABSTRACT FROM AUTHOR]

Background Actinic keratosis ( AK) severity is currently evaluated by subjective assessment of patients. Objectives To develop and perform an initial pilot validation of a new easy-to-use quantitative tool for assessing AK severity on the head. Methods The actinic keratosis area and severity index ( AKASI) for the head was developed based on a review of other severity scoring systems in dermatology, in particular the psoriasis area and severity index ( PASI). Initial validation was performed by 13 physicians assessing AK severity in 18 AK patients and two controls using a physician global assessment ( PGA) and AKASI. To determine an AKASI score, the head was divided into four regions (scalp, forehead, left/right cheek ear, chin and nose). In each region, the percentage of the area affected by AKs was estimated, and the severities of three clinical signs of AK were assessed: distribution, erythema and thickness. Results There was a strong correlation between AKASI and PGA scores (Pearson correlation coefficient: 0.86). AKASI was able to discriminate between different PGA categories: mean ( SD) AKASI increased from 2.88 (1.18) for 'light' to 5.33 (1.48) for 'moderate', 8.28 (1.89) for 'severe', and 8.73 (3.03) for 'very severe' PGA classification. The coefficient of variation for AKASI scores was low and relatively constant across all PGA categories. Conclusions Actinic keratosis area and severity index is proposed as a new quantitative tool for assessing AK severity on the head. It may be useful in the future evaluation of new AK treatments in clinical studies and the management of AK in daily practice. [ABSTRACT FROM AUTHOR]

Background The regrowth of a tumor after complete clinical response and the development of keratinocytic neoplasms while patients are still undergoing continuous vismodegib have stressed the importance of the accurate monitoring to detect recurrences earlier and ensure the best possible outcome. Objective The objective of this study was to determine the role of reflectance confocal microscopy ( RCM) in monitoring the response of locally advanced basal cell carcinoma (la BCC) to vismodegib and to discard secondary resistance. Methods Seven patients presenting with nine la BCC, were prospectively included and their response to this drug was assessed by means of clinical examination, dermoscopy, and RCM. The study was conducted at the Melanoma Unit in Hospital Clinic of Barcelona, between June 2012 and March 2013. Results Histologically confirmed lesion 10 mm or larger in diameter for which surgery was contraindicated and radiation therapy was inappropriate. The median patient age was 73 years and the most common histological type was infiltrating BCC. RCM allowed the identification of residual tumor in two lesions and to confirm complete response in the other four cases. Two patients developed new lesions within the tumor bed, they were assessed by RCM showing features of actinic keratosis which were confirmed by histopathology. Conclusion The use of in vivo RCM allowed the characterization of the dynamic morphologic changes in tumor response helping to better define partial response and to differentiate it from secondary resistance. Another interesting observation was the recognition of a phenomenon characterized by the development of keratinocytic neoplasms within the tumor bed. [ABSTRACT FROM AUTHOR]

Background Patient-reported outcome measures are very important outcomes. For specific diseases, health-related quality of life-instruments ( HRQoL) are increasingly used to provide data on patients' overall perceptions of the course of a given disease. Actinic keratoses ( AKs) are common keratotic lesions that occur on chronically sunlight-exposed skin. Only few studies regarding HRQoL in AKs have been made. Objective In order to be able to compare HRQoL among different countries and cultures, we aimed to translate and validate the Actinic Keratosis Quality of Life ( AKQoL) questionnaire into Spanish and quantify the impairment caused by AKs in Spanish patients. Methods The AKQoL was translated. Then, 15 patients with AKs were interviewed to ensure cultural adaption before it was tested in one hundred patients with AK lesions at the Melanoma Unit of Hospital Clinic in Barcelona. Results Validation showed high interitem correlations, as well as a high correlation of each item and the total score. Internal consistency (Cronbach's coefficient alpha) was also high at 0.91 and an alpha value of 0.90 at retest. The test-retest correlation was 0.96, and the intraclass coefficient was 0.98. Conclusion The presented data support the AKQoL Spanish version as a valid and reliable HRQoL questionnaire for the description of AK-related QoL and may provide a method for comparison of AK specific QoL between different cultures and countries. [ABSTRACT FROM AUTHOR]

Background Melanomas harbouring common genetic mutations might share certain morphological features detectable with dermoscopy and reflectance confocal microscopy. BRAF mutational status is crucial for the management of metastatic melanoma. Objectives To correlate the dermoscopic characteristics of primary cutaneous melanomas with BRAF mutational status. Furthermore, a subset of tumours has also been analysed for the presence of possible confocal features that might be linked with BRAF status. Methods Retrospectively acquired dermoscopic and confocal images of patients with melanoma in tertiary referral academic centres: Skin Cancer Unit in Reggio Emilia and at the Melanoma Unit in Barcelona. Kruskal-Wallis test, logistic regressions, univariate and multivariate analyses have been performed to find dermoscopic and confocal features significantly correlated with BRAF mutational status. Results Dermoscopically, the presence of irregular peripheral streaks and ulceration were positive predictors of BRAF-mutated melanomas with a statistically significance value, while dotted vessels were more represented in wild-type melanomas. None of the evaluated reflectance confocal microscopy features were correlated with genetic profiling. Conclusions Ulceration and irregular peripheral streaks represent dermoscopic feature indicative for BRAF-mutated melanoma, while dotted vessels are suggestive for wild-type melanoma. [ABSTRACT FROM AUTHOR]

Background Reflectance confocal microscopy (RCM) and high-definition optical coherence tomography (HD-OCT) allow the observation in vivo of dynamic changes in response to non-surgical treatment of actinic keratosis and field of cancerisation. Objective To non-invasively assess the pharmacodynamic changes induced by treatment with low dose 5-fluorouracil and 10% salicylic acid by means of RCM and high-definition OCT in field cancerization and actinic keratosis. Methods Twenty patients aged >50 years with diagnosis of actinic keratosis on the head and face and indication for treatment with 0.5% 5-fluorouracil and 10% salicylic acid were enrolled. An area of 25 cm² including visible type I and II AK and subclinical AK was treated once daily during 6 weeks and examination was performed with RCM and HD-OCT before treatment and 2 weeks after the end of treatment Results High-definition optical coherence tomography results at baseline of mean thickness of the stratum corneum and epidermis were in AK 10.4 (SD = 4.99) and 43.3 (SD = 24.01) μm respectively and in subclinical AK 3.7 (SD = 2.15) and 30.05 (SD = 16.85) μm. At week 8 (2 weeks after the end of treatment) measurements of stratum corneum and epidermis were significantly reduced in AK and subclinical AK for stratum corneum and epidermis. In RCM at week 8 scaling, detached corneocytes, atypical honeycomb, round nucleated cells in the spinosum granulosum layer, round vessels (dermal papillae), inflammatory cells and total AK score were significantly reduced in AK and subclinical AK. Conclusions Evaluation of AK and subclinical AK by RCM and HD-OCT showed objective improvement after treatment with 5-fluorouracil and 10% salicylic acid. These methods allowed the study of dynamic changes in the tissue at a subclinical level. [ABSTRACT FROM AUTHOR]

Background Naevus sebaceous is a congenital hamartoma commonly associated with the development of secondary neoplasms. There are sparse data relating to the dermoscopy of tumours arising in naevus sebaceous. Objectives To evaluate the dermoscopic features of a large series of neoplasms arising in naevus sebaceous. Methods Digital dermoscopic images of 58 histopathologically confirmed cases of secondary neoplasms arising in naevus sebaceous collected from 11 hospitals in Spain, France, Italy and Austria were evaluated for the presence of dermoscopic structures and patterns. Results The most frequent tumours collected were: trichoblastoma (39.6%), basal cell carcinoma (20.7%) and syringocystadenoma papilliferum (15.6%). The most remarkable findings were: (i) the pattern composed of asymmetrical large blue-grey ovoid nests was more common in basal cell carcinomas than in trichoblastoma (58.3% vs. 4.3%; P < 0.001) and the pattern composed of a symmetrical total large blue-grey ovoid nest (a blue-grey homogeneous area which occupies the whole lesion) was more common in trichoblastoma (82.6% vs. 16.6%; P < 0.001); (ii) the most frequent pattern associated with syringocystadenoma papilliferum was a symmetric, erythematous lesion with exophytic papillary structures, ulceration and vessels (55.5%); (iii) the most common pattern associated with apocrine hidrocystomas was a total symmetric homogeneous area and arborizing telangiectasias (60%). Conclusions Benign adnexal tumours associated with naevus sebaceous are dermoscopic mimickers of basal cell carcinomas. A pigmented nodule arising in a naevus sebaceous with a total blue large ovoid nest on dermoscopy could be a trichoblastoma, basal cell carcinoma, hidrocystoma or hidradenoma. Dermoscopy can be a useful diagnostic tool which generates a more accurate preoperative diagnosis. [ABSTRACT FROM AUTHOR]

Background Digital follow-up is a useful method for the detection of melanoma in atypical mole syndrome patients. The combination of digital follow-up (DFU) and reflectance confocal microscopy ( RCM) could be useful to increase the accuracy in the classification of equivocal lesions in atypical mole syndrome patients. Objectives To assess the impact of RCM analysis on sensitivity and specificity of digital follow-up in a high-risk melanoma setting. Methods Retrospective study with dermoscopy and RCM of consecutive equivocal atypical melanocytic lesions exhibiting changes in digital dermoscopy in a referral centre. Results Sixty-four lesions from 51 patients were included. Thirteen changing lesions (20.3%) corresponded to eight melanomas in situ and five invasive melanomas with Breslow less than 1 mm. Fifty-one lesions corresponded to melanocytic naevus with variable atypia. Total dermoscopy scores were not different between naevus and melanoma neither in the baseline (mean 5.06 and 5.24; P = 0.37) nor in the follow-up dermoscopic control (mean 5.44 and 5.55; P = 0.37). The only significant dermoscopic feature associated with melanoma in multivariate analysis was the presence of streaks after follow-up ( P = 0.027; OR = 3.6; CI 1.50-8.70). The confocal microscopy evaluation (by means both the Modena and Barcelona methods) showed a sensitivity and specificity for the diagnosis of melanoma of 100% and 69% respectively. Based on our experience, the combination of RCM and DFU could have avoided 35 of 51 nevi excised. Conclusions Reflectance confocal microscopy evaluation of equivocal lesions detected by DFU improved the accuracy in the detection of melanoma. The combination of dermoscopy, DFU and confocal microscopy in equivocal lesions can be useful to dramatically reduce the number of excisions of benign lesions in atypical mole syndrome patients. [ABSTRACT FROM AUTHOR]

Background Preliminary studies have described morphological features of basal cell carcinoma ( BCC) imaged by high-definition optical coherence tomography ( HD- OCT) and suggested that this technique may aid in its diagnosis and management. However, systematic studies evaluating the accuracy of HD- OCT for the diagnosis of BCC are lacking. Objective The aim of this study was to identify three-dimensional (3-D) HD- OCT features able i) to distinguish BCC from clinical BCC imitators and ii) to discriminate between the most common BCC subtypes. Based on these particular features, a diagnostic algorithm will be suggested. Method A total of 50 histopathologically confirmed BCCs (18 superficial, 19 nodular, 13 infiltrative) were imaged by HD- OCT at the centre of the lesion prior to standard surgical excision and subsequent histopathological analysis. Fifty images of clinical BCC imitators were also retrieved as a 'pitfalls' group. Results The simultaneous presence of grey/dark subepidermal (hemi-spherical) or intradermal lobulated structure(s) presenting a typical cockade feature in both HD- OCT modes was a significant feature for BCC diagnosis. Features discriminating between BCC subtypes were location of the roof of BCC lobules, vascular pattern of the papillary plexus and stretching effect on the stroma. Clinical BCC imitators such as actinic keratosis, compound and intradermal naevi, amelanotic melanoma, sebaceous hyperplasia and small haemangioma could be differentiated from BCC by means of HD- OCT. Conclusion This study provides a thorough description of 3-D HD- OCT features that can permit discrimination of BCC from clinical BCC imitators and differentiation of BCC subtypes. Based on these features, a diagnostic algorithm is proposed which requires additional validation, but enhances current understanding of the morphological correlates of HD- OCT images in skin. [ABSTRACT FROM AUTHOR]

Background Preliminary studies described morphological features of actinic keratosis ( AK) and squamous cell carcinoma ( SCC) imaged by High-Definition Optical Coherence Tomography ( HD- OCT) and suggested that this technique may aid in their diagnosis. However, systematic studies evaluating the accuracy of HD- OCT for the diagnosis of AK and SCC are lacking so far. Objective In this study, we sought to design an algorithm for AK classification that could (i) distinguish SCC from AK and normal skin, (ii) differentiate AK from normal skin and (iii) discriminate AKs with adnexal involvement from those without. Methods A total of 53 histopathologically confirmed lesions (37 AKs and 16 SCC) were imaged by HD- OCT. Fifty-three HD- OCT images of normal skin of healthy volunteers, with matched age, skin type and anatomic site, were taken as reference. By comparing these 106 en face and cross-sectional HD- OCT images, particular features were selected based on their potential to discriminate AK from normal skin and from SCC, and to assess adnexal involvement in AK. This study represents a training set not a testing set. Severe (>300 μm) hyperkeratotic AKs were not included in this study. Results Particular features with high Phi coefficient could be identified. The absence of an outlined dermo-epidermal junction ( DEJ) on cross-sectional images allowed discriminating SCC from AK and normal skin (Phi coefficient = 0.84). AK could be discriminated from normal skin in both imaging modes by the presence of alternating hyperkeratosis/parakeratosis in cross-sectional mode and/or variability in shape, size and reflectivity of cells (atypical honeycomb pattern) in en face mode. Adnexal involvement of AK could be assessed by the disappearance of the typical cocarde image of adnexal epithelium in en face mode. Conclusion This study provides select 3-D HD- OCT features having a potential to discriminate SCC from AK and normal skin. Based on these particular features with high Phi coefficient, a diagnostic algorithm is designed which will be used later in validation studies to determine HD- OCT accuracy in AK/ SCC classification. [ABSTRACT FROM AUTHOR]

In actinic keratosis (AK), clinical and subclinical lesions coexist across large areas of sun-exposed skin resulting in field cancerization. The lesions are part of a disease continuum which can progress into invasive squamous cell carcinoma (SCC). Conventional biopsy sampling together with histopathological analysis of the excised tissue is still the gold standard for differentially diagnosing AK from invasive SCC and identifying the characteristic pathophysiological features of these lesions. Given that biopsy sampling is invasive and not suited to the investigation of disease across large fields of skin, several imaging technologies have been applied to non-invasively investigate AK. Widely available imaging technologies such as cross-polarized light, fluorescence and dermoscopy can assist the dermatologist in diagnosing AK and in identifying different types of AK lesions. Modern imaging technologies such as reflectance confocal microscopy (RCM) and high-definition optical coherence tomography (HD-OCT) provide high-resolution images of the skin. These techniques can be used to image the histological changes that characterize AK and so can be used to diagnose the disease and its severity. They can also identify the presence of subclinical lesions and non-invasively monitor the effects of AK treatments on both subclinical and clinical lesions over time. Both RCM and HD-OCT have revealed a new vision of AK by visualizing in detail the cellular and histological changes that characterize both clinical and subclinical lesions, and confirming that the disease affects the entire sun-exposed field. As a consequence of these findings, the target for the treatment of AK now needs to be the detection and clearance of all clinical and subclinical lesions across the entire sun-exposed field. [ABSTRACT FROM AUTHOR]

Background Desmoplastic malignant melanoma ( DMM) is a rare and usually misdiagnosed type of melanoma. Delayed detection at complicated anatomical locations can lead to the necessity of alternative therapies. Objective Characterization of DMM on the nose, which is the second more frequent type of MM. Methods Review of case series of eight pathologically proven DMM on the nose from two referral centres with a mean follow-up of 69 ± 40.5 months. Results According to a single centre experience, there is a more than 70-fold increased risk of having a DMM on the nose compared with a non- DMM ( P < 0.0005, CI99% 16.3-317.3). Clinical and pathological misdiagnoses were frequent, only three of the eight cases were properly diagnosed and treated and indeed they did not experience relapses. Due to non-clinical suspicion and superficial biopsies, three cases were initially pathologically misdiagnosed as basal cell carcinomas and a nevus respectively. Atypical vessels and remnants of pigment on dermoscopy are indicative findings even in non-pigmented cases. Although not significant, the mean disease-free survival differed between cases with a correct initial management (four cases, 66.7 ± 57.3 months) in contrast to improper (four cases, 16.25 ± 18.9 months). Electrochemotherapy achieved a complete local control of disease in two cases unsuitable for surgery. Conclusions Use of dermoscopy and correctly selected biopsy of lesions on the face is mandatory to improve early diagnosis of DMM. Improper management of challenging cases implies a more complicated therapy and loco-regional invasion risk. Electrochemotherapy could be a promising therapy in local advanced tumours. [ABSTRACT FROM AUTHOR]

Background UV radiation and the presence of melanocytic nevi are the main risk factors of sporadic melanoma (MM). Protection of skin by an oral photoprotective agent would have substantial benefits. Objective We investigated the possible role of an oral Polypodium leucotomos (PL) extract to improve systemic photoprotection in patients at risk of skin cancer analyzing the ability to decrease UV-induced erythema. We also studied the interaction among MC1R polymorphisms and CDKN2A status with the minimal erythematous dose (MED) and their influence in the response after oral PL. Methods A total of 61 patients (25 with familial and/or multiple MM, 20 with sporadic MM and 16 with atypical mole syndrome without history of MM) were exposed to varying doses of artificial UVB radiation without and after oral administration of a total dose of 1080mg of PL. Results Oral PL treatment significantly increased the MED mean in all group patients (0.123 to 0.161 J/cm2, p<0.05). Although not significant, we noticed a stronger effect of PL on the MED of patients with familial MM compared to those with MM ( U=273, p=0.06). Among the patients with familial MM, those exhibiting a mutated CDKN2A and/or polymorphisms in MC1R had the bigger differences in response to treatment with PL. Limitations Reduced number of patients. No control population. Conclusions Administration of PL leads to a significant reduction of sensitivity to UVR (p<0.05) in all patients. Dark-eye patients and patients with higher UVR sensibility (lower basal MED) would be the most benefited from oral PL treatment. [ABSTRACT FROM AUTHOR]

It has been demonstrated that dermoscopic monitoring of melanocytic lesions allows for the recognition of melanoma in early stages while minimizing the excision of benign lesions. However, it is still pending to determine the real impact of digital follow-up in the clinical management of pigmented lesions. To assess the evidence of follow-up of melanocytic skin lesions with digital dermoscopy in the management of individuals at risk for melanoma by performing a meta-analysis. Medline database was screened, no limits in terms of date or language were applied. Original studies were selected when the following criteria were met: performed in clinical setting with clinical and dermoscopic evaluation made by physicians, data regarding population characteristics included, follow-up strategy used described. Fourteen of 145 retrieved references were retained. Included studies account for a total of 5787 patients (mean 445 per study) and 52 739 lesions monitored (mean per study 4057; range 272-11 396) with a mean of 12 lesions monitored per patient; a total of 4388 lesions (8.3%) were excised. The mean length of follow-up was 30 months. A mean of <1 lesion was excised per patient along the surveillance period. The number needed to monitor (NNM) ranged from 31 to 1008 (mean: 348) among eligible studies. For every additional month of monitoring, 1additional melanoma was detected. Using digital dermoscopy follow-up, the proportion of in situ melanoma and thin melanomas are higher than expected in general population. Chances to detect a melanoma during surveillance increase as the length of follow-up extends. [ABSTRACT FROM AUTHOR]

Background Little is known about the dermoscopic features of scalp tumours. Objective To determine the dermoscopic features of scalp tumours. Methods Retrospective analysis of dermoscopic images of histopathologically diagnosed scalp tumours from International Dermoscopy Society members. Results A total of 323 tumours of the scalp from 315 patients (mean age: 52 years; range 3-88 years) were analysed. Scalp nevi were significantly associated with young age (<30 years) and exhibited a globular or network pattern with central or perifollicular hypopigmentation. Melanoma and non-melanoma skin cancer were associated with male gender, androgenetic alopecia, age >65 years and sun damage. Atypical network and regression were predictive for thin (≤1 mm) melanomas, whereas advanced melanomas (tumour thickness > 1 mm) revealed blue white veil, unspecific patterns and irregular black blotches or dots. Conclusions The data collected provide a new knowledge regarding the clinical and dermoscopy features of pigmented scalp tumours. [ABSTRACT FROM AUTHOR]

Patients with genodermatosis such as Gorlin syndrome (GS) and Xeroderma pigmentosum (XP) require a close follow-up for early diagnosis and treatment of skin cancer. We aimed to evaluate the efficacy of methyl-aminolevulinate (MAL) photodynamic therapy (PDT) in basal cell carcinomas (BCCs) from patients with GS and XP, and to determine the utility of reflectance confocal microscopy (RCM) in the diagnosis and the evaluation of therapeutic response. We included four patients with GS and two siblings with XP. Single or multiple lesions in localized areas were treated with 1-3 cycles of MAL PDT. RCM was performed before and 3 months after the treatment in target lesions in all the patients. Patients were followed up for 3 years. In XP patients, we treated 13 pigmented BCCs on the face. All the lesions responded to the treatment and six lesions showed a complete clinical clearing. In GS patients, facial or trunk areas with multiple BCCs were treated (up to 200). Complete clinical remission was obtained in 25-67% of the lesions. Some nodular and pigmented lesions failed to achieve a complete remission. RCM could identify already described confocal features for BCC. Tumour remissions could be assessed by this technique. Methyl-aminolevulinate PDT may be useful for the treatment of superficial BCC in GS and XP. In some nodular lesions, PDT may complement surgery reducing tumour size. RCM may be regarded in the future as a complementary technique in BCC for the diagnosis and post-treatment assessment to non-invasive therapeutic modalities. [ABSTRACT FROM AUTHOR]

Trichothiodystrophy (TTD) is a hair abnormality that may be associated with a large number of alterations affecting the skin phenotype and skin appendages, nervous system, eyes, bones, and immune, gonadal, and endocrine systems. We report the first case of TTD associated with a urologic malformation and primary hypercalciuria. Our patient had congenital ichthyosis, physical and mental retardation, and a dysmorphic facies associated with a complex urologic malformation and primary hypercalciuria. Characteristic features of his hair under microscopic examination (trichoschisis, alternating light and dark bands under polarizing microscopy, and a severely defective cuticle) and low sulfur content by radiographic microanalysis confirmed the diagnosis. We discuss the meaning of this new association in the spectrum of abnormalities related to TTD. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning a case of molluscum contagiosum.

Background: There is currently no staging system for cutaneous squamous cell carcinoma (cSCC) that is adapted to decision-making and universally used. Experts have unconscious ability to simplify the heterogeneity of clinical situations into a few relevant groups to drive their therapeutic decisions. Therefore, we have used unsupervised clustering of real cases by experts to generate an operational classification of cSCCs, an approach that was successful for basal cell carcinomas., Objective: To generate a consensual and operational classification of cSCCs., Method: Unsupervised independent clustering of 248 cases of cSCCs considered difficult-to-treat. Eighteen international experts from different specialties classified these cases into what they considered homogeneous clusters useful for management, each with freedom regarding clustering criteria. Convergences and divergences between clustering were analysed using a similarity matrix, the K-mean approach and the average silhouette method. Mathematical modelling was used to look for the best consensual clustering. The operability of the derived classification was validated on 23 new practitioners., Results: Despite the high heterogeneity of the clinical cases, a mathematical consensus was observed. It was best represented by a partition into five clusters, which appeared a posteriori to describe different clinical scenarios. Applicability of this classification was shown by a good concordance (94%) in the allocation of cases between the new practitioners and the 18 experts. An additional group of easy-to-treat cSCC was included, resulting in a six-group final classification: easy-to-treat/complex to treat due to tumour and/or patient characteristics/multiple/locally advanced/regional disease/visceral metastases., Conclusion: Given the methodology based on the convergence of unguided intuitive clustering of cases by experts, this new classification is relevant for clinical practice. It does not compete with staging systems, but they may complement each other, whether the objective is to select the best therapeutic approach in tumour boards or to design homogeneous groups for trials., (© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: The detection of cutaneous metastases (CMs) from various primary tumours represents a diagnostic challenge., Objectives: Our aim was to evaluate the general characteristics and dermatoscopic features of CMs from different primary tumours., Methods: Retrospective, multicentre, descriptive, cross-sectional study of biopsy-proven CMs., Results: We included 583 patients (247 females, median age: 64 years, 25%-75% percentiles: 54-74 years) with 632 CMs, of which 52.2% (n = 330) were local, and 26.7% (n = 169) were distant. The most common primary tumours were melanomas (n = 474) and breast cancer (n = 59). Most non-melanoma CMs were non-pigmented (n = 151, 95.6%). Of 169 distant metastases, 54 (32.0%) appeared on the head and neck region. On dermatoscopy, pigmented melanoma metastases were frequently structureless blue (63.6%, n = 201), while amelanotic metastases were typified by linear serpentine vessels and a white structureless pattern. No significant difference was found between amelanotic melanoma metastases and CMs of other primary tumours., Conclusions: The head and neck area is a common site for distant CMs. Our study confirms that most pigmented melanoma metastasis are structureless blue on dermatoscopy and may mimic blue nevi. Amelanotic metastases are typified by linear serpentine vessels and a white structureless pattern, regardless of the primary tumour., (© 2024 European Academy of Dermatology and Venereology.)

Actinic keratoses (AK) are common skin lesions associated with chronic exposure to sun. They are believed to be precursors of malignancy as they potentially may progress to invasive squamous cell carcinomas. The goal of current therapies is to reduce the number of AK and to prevent future cancer development. This review aims at providing an overview of the hallmarks of AK and skin field cancerization. We discuss epidemiology trends, risk factors and the state of the art and evidence of the current treatments. We review key figures of AK prevalence from different countries with regard to skin cancer risk and the associated economic burden of AK. We discuss the mutational status in AK lesions and the difficulties encountered by clinicians in evaluating AK visible and invisible lesions, referring to the concept of field cancerization. Based on a systematic literature review, we further evaluate the available treatment options. The presence of subclinical skin alterations in the periphery of visible AK lesions has gained a particular attention as those non-visible lesions are known to contain the same genetic changes as those found in the AK lesions themselves, prompting the concept of 'field cancerization'. Therefore, AK treatment guidelines now recognize the importance of treating the field in patients with AK. A recent systematic literature review and network meta-analysis showed that 5-FU interventions were associated with the best efficacy and a satisfactory acceptability profile compared with other field-directed therapies used in the treatment of AK. Although AK are considered quite common, they lack an accurate descriptive definition and conclusive epidemiologic data. Limited public awareness is a barrier to early and effective treatment, including prevention strategies. While different treatment options are available, there is still a limited understanding of long-term outcomes of treatment as measured by recurrence of cancer prevention., (© 2024 European Academy of Dermatology and Venereology.)