Pattern Analysis of Benign and Malignant Atypical Melanocytic Skin Lesions of Palms and Soles: Variations of Dermoscopic Features According to Anatomic Site and Personal Experience.

Background: The differential diagnosis of atypical melanocytic skin lesions localized on palms and soles represents a diagnostic challenge: indeed, this spectrum encompasses atypical nevi (AN) and early-stage melanomas (EN) displaying overlapping clinical and dermoscopic features. This often generates unnecessary excisions or delayed diagnosis. Investigations to date were mostly carried out in specific populations, focusing either on acrolentiginous melanomas or morphologically typical acquired nevi. Aims: To investigate the dermoscopic features of atypical melanocytic palmoplantar skin lesions (aMPPLs) as evaluated by variously skilled dermatologists and assess their concordance; to investigate the variations in dermoscopic appearance according to precise location on palms and soles; to detect the features with the strongest association with malignancy/benignity in each specific site. Methods: A dataset of 471 aMPPLs-excised in the suspect of malignancy-was collected from 10 European Centers, including a standardized dermoscopic picture (17×) and lesion/patient metadata. An anatomical classification into 17 subareas was considered, along with an anatomo-functional classification considering pressure/friction, (4 macroareas). A total of 156 participants (95 with less than 5 years of experience in dermoscopy and 61 with ≥than 5 years) from 17 countries performed a blinded tele-dermoscopic pattern analysis over 20 cases through a specifically realized web platform. Results: A total of 37,440 dermoscopic evaluations were obtained over 94 (20%) EM and 377 (80%) AN. The areas with the highest density of EM compared to AN were the heel (40.3% EM/aMPPLs) of the sole and the "fingers area" (33%EM/aMPPLs) of the palm, both characterized by intense/chronic traumatism/friction. Globally, the recognition rates of 12 dermoscopic patterns were non statistically different between 95 dermatology residents and 61 specialists: aMPPLs in the plantar arch appeared to be the most "difficult" to diagnose, the parallel ridge pattern was poorly recognized and irregular/regular fibrillar patterns often misinterpreted. Regarding the aMPPL of the "heel area", the parallel furrow pattern (p = 0.014) and lattice-like pattern (p = 0.001) significantly discriminated benign cases, while asymmetry of colors (p = 0.002) and regression structures (p = 0.025) malignant ones. In aMPPLs of the "plantar arch", the lattice-like pattern (p = 0.012) was significant for benignity and asymmetry of structures, asymmetry of colors, regression structures, or blue-white veil for malignancy. In palmar lesions, no data were significant in the discrimination between malignant and benign aMPPLs. Conclusions: This study highlights that (i) the pattern analysis of aMPPLs is challenging for both experienced and novice dermoscopists; (ii) the histological distribution varies according to the anatomo-functional classification; and (iii) different dermoscopic patterns are able to discriminate malignant from benign aMPPLs within specific plantar and palmar areas.

Therapeutic Potential of Targeting the JAK/STAT Pathway in Psoriasis: Focus on TYK2 Inhibition.

Psoriasis is an inflammatory skin disease with a chronic relapsing course and an often-detrimental impact on patients' quality of life. Thanks to incredible advances in research over the past few decades, the therapeutic armamentarium of psoriasis is now reasonably broad and structured, with several therapeutic agents that have demonstrated successful long-term control of this condition. However, there are still unfulfilled gaps resulting from the inherent limitations of existing therapies, which have paved the way for the identification of new therapeutic strategies or the improvement of existing ones. A great deal of attention has recently been paid to the JAK/STAT pathway, playing a crucial role in chronic inflammatory skin diseases, including psoriasis. Indeed, in a disease with such a complex pathogenesis, the possibility to antagonize multiple molecular pathways via JAK/STAT inhibition offers an undeniable therapeutic advantage. However, data from clinical trials evaluating the use of oral JAK inhibitors in immune-mediated disorders, such as RA, have arisen safety concerns, suggesting a potentially increased risk of class-specific AEs such as infections, venous thromboembolism, and malignancies. New molecules are currently under investigation for the treatment of psoriasis, such as deucravacitinib, an oral selective inhibitor that binds to the regulatory domain of TYK2, brepocitinib (PF-06700841) and PF-06826647 that bind to the active site in the catalytic domain. Due to the selective TYK2 blockade allowing the inhibition of key cytokine-mediated signals, such as those induced by IL-12 and IL-23, anti-TYK2 agents appear to be very promising as the safety profile seems to be superior compared with pan-JAK inhibitors. The aim of our review is to thoroughly explore the rationale behind the usage of JAK inhibitors in PsO, their efficacy and safety profiles, with a special focus on oral TYK2 inhibitors, as well as to provide a forward-looking update on novel therapeutic strategies targeting the TYK2 pathway in psoriasis.

Correlation between super-high magnification (400x) dermoscopy and reflectance confocal microscopy for the diagnosis of melanosis and other pigmented genital lesions.

The clinical diagnosis of pigmented genital lesions is challenging. Reflectance confocal microscopy (RCM) is effective for diagnosis but is limited in its application due to elevated costs. A more affordable dermatoscope with a 400x magnification (D400) has recently been brought to market. The aim of our study was to compare these two imaging techniques for the analysis of pigmented genital tumours. An observational, prospective and mono-centric study was carried out from October 2017 to May 2019, in which clinical, dermatoscopic (20x and 400x) and RCM data from 207 pigmented genital lesions were collected. The images generated via D400 and RCM were analysed by three expert investigators. Similarities between the criteria observed using D400 and RCM were evaluated by each investigator. In total, 207 lesions were included: 183 melanosis, 19 nevi, one basal cell carcinoma (BCC), two condylomas and two melanomas in situ. Our series correlates well with data found in the literature especially for the distribution of different lesions, their topography, and their aspect using x20 dermatoscopy and RCM. Pattern and cell criteria defined using RCM largely paralleled those observed with D400 for all three investigators. Correlation between D400 and RCM was moderate to strong with regards to the identification of the ring pattern and clustered round cells, strong for dendritic and plump cells, and perfect for isolated round cells and spindle cells. D400 is an easy-to-use, cost-effective alternative for the analysis of pigmented genital lesions, particularly for melanosis.

Understanding the Dermoscopic Patterns of Basal Cell Carcinoma Using Line-Field Confocal Tomography.

Basal cell carcinoma (BCC) is the most frequent malignancy in the general population. To date, dermoscopy is considered a key tool for the diagnosis of BCC; nevertheless, line-field confocal optical coherence tomography (LC-OCT), a new non-invasive optical technique, has become increasingly important in clinical practice, allowing for in vivo imaging at cellular resolution. The present study aimed to investigate the possible correlation between the dermoscopic features of BCC and their LC-OCT counterparts. In total, 100 histopathologically confirmed BCC cases were collected at the Dermatologic Clinic of the University of Siena, Italy. Predefined dermoscopic and LC-OCT criteria were retrospectively evaluated, and their frequencies were calculated. The mean (SD) age of our cohort was 65.46 (13.36) years. Overall, BCC lesions were mainly located on the head (49%), and they were predominantly dermoscopically pigmented (59%). Interestingly, all dermoscopic features considered had a statistically significant agreement with the LC-OCT criteria (all p < 0.05). In conclusion, our results showed that dermoscopic patterns may be associated with LC-OCT findings, potentially increasing accuracy in BCC diagnosis. However, further studies are needed in this field.

Non-Invasive Imaging for the Diagnosis of Genital Warts and Their Imitators.

Genital warts are the most frequent sexually transmitted disease. Their clinical diagnosis is not always easy, and invasive skin biopsies for histological examination should be performed in these cases. The aim of the study was to investigate the use of non-invasive imaging techniques for the diagnosis of genital warts and their imitators. We retrospectively evaluated dermoscopy, reflectance confocal microscopy (RCM), and line-filed confocal microscopy (LC-OCT) images of nine patients with 19 warts of the mucous membranes and five patients with lesions that clinically mimic genital warts, including 12 molluscum contagiosum, 1 Fordyce's spot and one case of multiple acquired lymphangiomas. Most genital warts (15; 79%) showed dilated vessels surrounded by a whitish halo at dermoscopy. RCM and the new device LC-OCT could identify near histologic features such as the presence of hyperkeratosis, acanthosis, papillomatosis and enlarged vessels in all genital warts. However, the identification of koilocytes, which are the hallmark for the diagnosis of warts, was still difficult using both techniques. Non-invasive imaging techniques could also offer clues for the correct diagnosis of the imitators. This study confirmed the usefulness of dermoscopy in recognizing a precise pattern in warts and showed the potential use of RCM and LC-OCT to add additional findings to the clinical and dermoscopic examination.

Design of a new 3D printed all-in-one magnetic smartphone adapter for fundus and anterior segment imaging.

PURPOSE: To describe and validate a 3D-printed adapter tool which could be used with either a slit lamp or a condensing lens, interchangeable between devices through magnetic fastening, in order to provide physicians a quick, easy and effective method of obtaining clinical photos. MATERIALS AND METHODS: Three specialists, with at least 4-year experience in ophthalmology, gave a rate of image quality obtained by our device and the diagnostic confidence grade. The 3 specialists conducted each 13 or 14 examinations with the smartphone and magnetic adapter. At the end of evaluation, they rated with the Likert scale the ease of use of the device in obtaining clinical images of the anterior segment and ocular fundus respectively. RESULTS: Data of quality perception and confidence demonstrated high values not dissimilar to the "de visu" eye examination. Moreover the instrument we designed turned out to be very user friendly. CONCLUSION: Our adapter coupled with a modern smartphone was able to obtain 4k images and videos of anterior segment, central and peripheral fundus, in an easy and inexpensive way.

A European Multicentric Investigation of Atypical Melanocytic Skin Lesions of Palms and Soles: The iDScore-PalmoPlantar Database.

Background: The differential diagnosis of atypical melanocytic palmoplantar skin lesions (aMPLs) represents a diagnostic challenge, including atypical nevi (AN) and early melanomas (MMs) that display overlapping clinical and dermoscopic features. We aimed to set up a multicentric dataset of aMPL dermoscopic cases paired with multiple anamnestic risk factors and demographic and morphologic data. Methods: Each aMPL case was paired with a dermoscopic and clinical picture and a series of lesion-related data (maximum diameter value; location on the palm/sole in 17 areas; histologic diagnosis; and patient-related data (age, sex, family history of melanoma/sunburns, phototype, pheomelanin, eye/hair color, multiple/dysplastic body nevi, and traumatism on palms/soles). Results: A total of 542 aMPL cases-113 MM and 429 AN-were collected from 195 males and 347 females. No sex prevalence was found for melanomas, while women were found to have relatively more nevi. Melanomas were prevalent on the heel, plantar arch, and fingers in patients aged 65.3 on average, with an average diameter of 17 mm. Atypical nevi were prevalent on the plantar arch and palmar area of patients aged 41.33 on average, with an average diameter of 7 mm. Conclusions: Keeping in mind the risk profile of an aMPL patient can help obtain a timely differentiation between malignant/benign cases, thus avoiding delayed and inappropriate excision, respectively, with the latter often causing discomfort/dysfunctional scarring, especially at acral sites.

Dermatoscopic patterns of cutaneous metastases: A multicentre cross-sectional study of the International Dermoscopy Society.

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.

Psoriasis and Fibromyalgia: A Systematic Review.

Psoriasis is a chronic inflammatory cutaneous condition characterized by several comorbidities, including musculoskeletal disorders. While the association with psoriatic arthritis has been widely addressed in literature, the aim of the present systematic review was to identify all available evidence on the relationship between psoriasis and fibromyalgia, a musculoskeletal syndrome primarily characterized by chronic widespread pain. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and MedLine and Web of Science (WOS) databases were searched for literature up to March 2023. After the removal of duplicate records, a total of 11 articles were deemed eligible for inclusion in a qualitative synthesis. Our results suggested that psoriatic patients had a higher prevalence of fibromyalgia (8-30%), with a very high impact on symptoms of psoriasis. Moreover, fibromyalgic patients had a slightly increased prevalence of psoriasis (2.2-6.7%) compared to the control groups. Finally, several studies demonstrated the substantial impact of fibromyalgia on psoriatic outcome measures in patients with concomitant psoriatic arthritis. In conclusion, available data support a potential interplay between psoriasis and fibromyalgia, but further research is encouraged in this area.

Position statement of the EADV Artificial Intelligence (AI) Task Force on AI-assisted smartphone apps and web-based services for skin disease.

BACKGROUND: As the use of smartphones continues to surge globally, mobile applications (apps) have become a powerful tool for healthcare engagement. Prominent among these are dermatology apps powered by Artificial Intelligence (AI), which provide immediate diagnostic guidance and educational resources for skin diseases, including skin cancer. OBJECTIVE: This article, authored by the EADV AI Task Force, seeks to offer insights and recommendations for the present and future deployment of AI-assisted smartphone applications (apps) and web-based services for skin diseases with emphasis on skin cancer detection. METHODS: An initial position statement was drafted on a comprehensive literature review, which was subsequently refined through two rounds of digital discussions and meticulous feedback by the EADV AI Task Force, ensuring its accuracy, clarity and relevance. RESULTS: Eight key considerations were identified, including risks associated with inaccuracy and improper user education, a decline in professional skills, the influence of non-medical commercial interests, data security, direct and indirect costs, regulatory approval and the necessity of multidisciplinary implementation. Following these considerations, three main recommendations were formulated: (1) to ensure user trust, app developers should prioritize transparency in data quality, accuracy, intended use, privacy and costs; (2) Apps and web-based services should ensure a uniform user experience for diverse groups of patients; (3) European authorities should adopt a rigorous and consistent regulatory framework for dermatology apps to ensure their safety and accuracy for users. CONCLUSIONS: The utilisation of AI-assisted smartphone apps and web-based services in diagnosing and treating skin diseases has the potential to greatly benefit patients in their dermatology journeys. By prioritising innovation, fostering collaboration and implementing effective regulations, we can ensure the successful integration of these apps into clinical practice.

Signaling Pathways and Therapeutic Strategies in Advanced Basal Cell Carcinoma.

Non-melanoma skin cancers (NMSCs) are the most common human neoplasms world-wide. In detail, basal cell carcinoma (BCC) is the most frequent malignancy in the fair-skinned population. The incidence of BCC remains difficult to assess due to the poor registration practice; however, it has been increasing in the last few years. Approximately, 85% of sporadic BCCs carry mutations in Hedgehog pathway genes, especially in PTCH, SUFU and SMO genes, which lead to the aberrant activation of GLI transcriptional factors, typically silent in cells of adult individuals. The management of advanced BCC (aBCC), both metastatic (mBCC) and locally advanced BCC (laBCC), not candidates for surgical excision or radiotherapy, remains challenging. The discovery of mutations in the Hh signaling pathway has paved the way for the development of Hh pathway inhibiting agents, such as vismodegib and sonidegib, which have represented a breakthrough in the aBCC management. However, the use of these agents is limited by the frequent occurrence of adverse events or the development of drug resistance. In this review, we thoroughly describe the current knowledge regarding the available options for the pharmacological management of aBCCs and provide a forward-looking update on novel therapeutic strategies that could enrich the therapeutic armamentarium of BCC in the near future.

Characteristics of Primary Cutaneous Lymphoma in Italy: A Tertiary Care, Single-Center Study.

Data on primary cutaneous lymphomas (PCLs) patients in the Italian population are limited, and, despite the existence of several treatment options, the management of those patients remains challenging. Our study aimed to investigate the clinical and therapeutic features of PCL patients in a referral center in Italy. We conducted a retrospective study on 100 consecutive PCL patients between January 2017 and December 2022. The mean (SD) age of our cohort was 70.33 (14.14) years. Cutaneous T-cell lymphomas (CTCLs) represented 65% of all cases; the majority were mycosis fungoides (42%), followed by cases of Sezary syndrome (10%) and primary cutaneous anaplastic large cell lymphoma (4%). Cutaneous B-cell lymphomas (CBCLs) accounted for 35 % of PCLs, with 15 cases of primary cutaneous follicle center lymphoma, 10 cases of primary cutaneous diffuse large B-cell lymphoma leg type, and 9 cases of marginal zone B-cell lymphoma. A higher frequency of pruritus (p = 0.008) and higher peripheral blood levels of beta-2 microglobulin (p ≤ 0.001) and lactate dehydrogenase (p = 0.025) were found in CTCLs compared to those of CBCLs. Considering all therapeutic lines performed, treatments were extremely heterogeneous and skin-directed therapies represented the most frequently used approach. Our study confirms the distribution of PCL subtypes formerly reported in the literature and highlights the utility of real-life data in treatments to improve the current management of PCL patients.

Line-Field Confocal Optical Coherence Tomography for the Diagnosis of Skin Carcinomas: Real-Life Data over Three Years.

Line-field confocal optical coherence tomography (LC-OCT) can help the clinical diagnosis of skin diseases. The present study aimed to evaluate the sensitivity, specificity, and diagnostic accuracy of LC-OCT for the diagnosis of the most frequent non-melanoma skin cancers (NMSCs), i.e., basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Comparing LC-OCT diagnostic performances with those of dermoscopy, histopathological examination was used as a gold standard. For every study endpoint, the diagnostic ability of LC-OCT revealed superiority over the dermoscopic examination. In particular, a significant increase in specificity was observed. Sensitivity, specificity, and diagnostic accuracy of dermoscopy and LC-OCT for the diagnosis of malignancy were, respectively, 0.97 (CI 0.94-0.99), 0.43 (CI 0.36-0.51), and 0.77 (CI 0.72-0.81) for dermoscopy and 0.99 (CI 0.97-1.00), 0.90 (CI 0.84-0.94), and 0.96 (CI 0.93-0.97) for LC-OCT. The positive predictive value (PPV) resulted in 0.74 (CI 0.69-0.78) for dermoscopy and 0.94 (CI 0.91-0.97) for LC-OCT, and the negative predictive value (NPV) was 0.89 (CI 0.81-0.95) for dermoscopy and 0.98 (CI 0.95-1.00) for LC-OCT. Finally, our real-life study showed a potentially important role of LC-OCT in the non-invasive diagnosis of NMSCs, especially BCC. The real-time imaging technique could spare unnecessary biopsies with an increased sensitivity, a much higher specificity, and better accuracy than clinical assessment with dermoscopy alone.

Unfolding dermatologic spectrum of Behçet's disease in Italy: real-life data from the International AIDA Network Behçet's disease Registry.

Behçet's disease (BD) is a heterogeneous multifactorial autoinflammatory disease characterized by a plethora of clinical manifestations. Cutaneous lesions are considered hallmarks of the disease. However, their evolution over time and a thorough description are scarcely reported in non-endemic regions. The aim of this study was to detail BD skin manifestations and their evolution over time in Italy, as well as the dermatological prognostic impact of specific cutaneous features in long-standing disease. Data were collected in a double fashion, both retrospectively and prospectively, from the AutoInflammatory Disease Alliance (AIDA) international registry dedicated to BD, between January 2022 and December 2022. A total of 458 Italian patients were included. When assessing skin manifestations course, the constant or sporadic presence or absence of cutaneous involvement between onset and follow-up was considered. Oral ulcers (OU) (88.4%) and genital ulcers (GU) (52.6%), followed by skin involvement (53.7%) represented the most common presenting mucocutaneous manifestations at disease onset. Up to the time of enrolment into the AIDA registry, 411 (93.8%) patients had suffered from OU and 252 (57.9%) from GU; pseudofolliculitis (PF) accounted for the most common skin manifestation (170 patients, 37.1%), followed by erythema nodosum (EN) (102 patients, 22.3%), skin ulcers (9 patients, 2%) and pyoderma gangrenosum (4 patients, 0.9%). A prospective follow-up visit was reported in 261/458 patients; 24/148 (16.2%) subjects with skin involvement as early as BD onset maintained cutaneous lesions for the entire period of observation, while 120 (44.1%) patients suffered from sporadic skin involvement. Conversely, 94/113 (83.2%) with no skin involvement at disease onset did not develop skin lesions thereafter. At follow-up visits, cutaneous involvement was observed in 52 (20%) patients, with a statistically significant association between PF and constant skin involvement (p = 0.031). BD in Italy is characterized by a wide spectrum of clinical presentations and skin manifestations in line with what is described in endemic countries. Patients with skin disease at the onset are likely to present persistent cutaneous involvement thereafter; mucocutaneous lesions observed at the onset, especially PF, could represent a warning sign for future persistent skin involvement requiring closer dermatological care.