Background: Sonidegib displays class-specific adverse events (AEs), which impair therapeutic adherence. Every-other-day administration is within the label of sonidegib approval. Objective: to investigate the effectiveness and safety profile of every-other-day sonidegib in locally advanced basal cell carcinoma (laBCC) patients after a course of once-daily sonidegib. Methods: a multicenter retrospective observational study was performed at 15 Italian tertiary-referral centers (January 2016 - May 2024). Fisher's exact and Mann-Whitney test detected differences between the cohorts. Kaplan-Meier method estimated progression free survival (PFS). Univariate and multivariate logistic regressions investigated the association with switching to the every-other-day schedule. Results: 165 laBCC patients were enrolled, of whom 60 switched from once-daily to every-other-day sonidegib. Median sonidegib treatment duration was 14 months (range: 1-26) in the continuous regimen cohort, and 23 months (range: 6-29) in the reduced regimen cohort, p value < 0.0001. The objective response rate (ORR) was 80.8 % (95 % confidence interval [CI]: 87.4-72) and 84.8 % (95 % CI: 91.6-74.3) for patients on the once-daily and on the every-other-day sonidegib schedule, respectively. Median duration of response was 9.5 months (range: 1-37) and 6 months (range: 1-28) in the continuous and in the reduced regimen cohorts, respectively. PFS probability was reduced in the every-other-day sonidegib group compared to the once-daily group (hazard ratio: 4.8, 95 % CI: 1.10-21.27; p = 0.003). 62.6 % and 19.7 % patients experienced at least one AE on the once-daily and on the every-other-day schedule, respectively, p value < 0.0001. Conclusion: Switch to the every-other-day sonidegib schedule is safe and effective, albeit with reduced tumor control in the long-term.

BACKGROUND:Flat head/neck pigmented macules can be diagnostically challenging. OBJECTIVE:To assess the impact of reflectance confocal microscopy (RCM) integration to dermoscopic triage of equivocal lesions. METHODS:Prospective multicenter study of equivocal flat macules. Lesions suspicious or discordant were biopsied/excised; double-negative lesions were followed ≥1 year. Histopathology served as reference standard. RESULTS:A total of 2006 lesions from 801 patients (mean age 66.2 years) were evaluated. After dermoscopy-RCM integration, 236/2006 (11.8%) lesions were managed as malignant (226 biopsied/excised; 10 noninvasively treated: 8 basal cell carcinoma [BCC] and 2 lentigo maligna [LM]). Twenty-six lesions changed at follow-up and were removed, with 4 malignancies (0.4%; 3 LM, 1 BCC). Histology (n = 252) confirmed 114 malignancies (62 LM/lentigo maligna melanoma [LMM]; 52 BCC/squamous cell carcinoma [SCC]). Dermoscopy detected 54.8% of LM/LMM and 90.4% of BCC/SCC; RCM correctly diagnosed 91.9% of LM/LMM and 94.2% of BCC/SCC. LIMITATIONS:Verification and selection biases and follow-up losses. CONCLUSION:Integrating RCM significantly improves LM/LMM sensitivity detection and specificity for benign lesions compared to dermoscopy alone, minimizing overtreatment and missed malignancies. Although a small residual risk of missed malignancy persists, the combined approach offers a highly safe, noninvasive pathway for managing equivocal lesions in cosmetically sensitive areas.

BACKGROUND:Basal cell carcinoma (BCC) is the most prevalent form of skin cancer. Accurate histological subtyping is essential for appropriate therapeutic planning, particularly for infiltrative variants associated with higher recurrence rates. Noninvasive imaging modalities such as dermoscopy and reflectance confocal microscopy (RCM) may enhance the diagnostic precision of BCC subtyping prior to treatment. OBJECTIVES:To validate dermoscopic criteria and identify RCM features associated with distinct BCC subtypes in a larger cohort and to improve the accuracy of noninvasive BCC subtyping and support precision treatment planning. METHODS:This was a prospective multicentre study conducted between August 2017 and June 2019 across three centres in Northern Italy. In total, 281 histologically confirmed BCCs from 256 patients were analysed. Each lesion underwent standardized clinical, dermoscopic and handheld RCM evaluation prior to biopsy. Subtype-specific features were recorded and correlated with histopathology. Interobserver agreement was assessed using Cohen's kappa, and diagnostic performance was evaluated via sensitivity, specificity and the area under the receiver operating characteristic curve (AUC). The study was registered at Clinicaltrials.gov (NCT04789421). RESULTS:Among the 281 BCCs, 15% were superficial, 38% were nodular and 47% were infiltrative. Dermoscopically, superficial BCCs exhibited brown globules and shiny white-red structureless areas; nodular BCCs presented blue structures, arborizing vessels and ulceration; infiltrative BCCs showed white porcelain areas and lacked pigmentation. RCM identified streaming and cords in superficial BCCs (P = 0.003; threefold risk), large tumour islands in nodular BCCs, and dark silhouettes in infiltrative BCCs (P = 0.005; two-threefold risk). Diagnostic accuracy improved with combined dermoscopy and RCM. Sensitivity for superficial BCC increased from 74.4% [95% confidence interval (CI) 60.2-85.8] to 81.4% (95% CI 68.1-91.0), specificity from 97.9% (95% CI 95.5-99.5) to 98.3% (95% CI 96.1-99.5), and AUC reached 0.899. CONCLUSIONS:The integration of dermoscopic and RCM findings significantly enhances the noninvasive preoperative classification of BCC subtypes. This approach improves diagnostic accuracy and may inform more precise, subtype-tailored management, reducing treatment failures and supporting personalized dermatological care.

Nevus-associated melanoma (NAM) is histologically defined by coexisting nevus and melanoma components, yet the nevus component is frequently not visible on dermoscopy. We performed a retrospective, single-centre observational study including histologically diagnosed NAMs (2011-2024). Dermoscopic images were assessed independently by two readers. Histopathology was systematically revised to quantify nevus proportion, size, and depth. Univariate and multivariable logistic regression evaluated associations with (a) invasive vs. in situ NAM and (b) dermoscopically visible vs. non-visible nevus component. Among 340 NAMs, 36.8% were in situ and 63.2% invasive. A dermoscopic nevus was visible in 45.6%. In multivariable analysis, nevus visibility under dermoscopy was independently associated with histopathologic features such as larger nevus size, particularly 2.1-4 mm (OR 2.5, 95% CI 1.3-4.6), 4.1-10 mm (OR 3.7, 95% CI 2.0-7.0), and > 10 mm (OR 5.3, 95% CI 1.4-20.0), whereas deep nevus location (OR 0.3, 95% CI 0.2-0.5) and ulceration (OR 0.2, 95% CI 0.1-0.6) reduced visibility. Invasive NAM was independently associated with a visible nevus component under dermoscopy (OR 2.5, 95% CI 1.7-3.7), shiny white structures (OR 5.0, 95% CI 2.6-9.4), negative pigment network (OR 1.9, 95% CI 1.2-3.2), and blue-white veil (OR 8.3, 95% CI 4.5-15.4), whereas atypical pigment network and melanoma pigmentation were inversely associated with invasion. Dermoscopic nevus visibility in NAM is mainly determined by nevus size and depth, while melanoma-related changes, particularly ulceration, can obscure the nevus component. Dermoscopic markers of invasiveness should prompt timely management even when an associated nevus is suspected.

BACKGROUND:Chronic skin ulcers represent a significant burden for healthcare systems due to their high prevalence, prolonged healing times and recurrence rates. Despite their impact, the organization and resources of outpatient ulcer clinics remain poorly characterized worldwide. The aim of this study was to evaluate the organization of outpatient clinics for chronic skin ulcers in the Italian dermatological setting. METHODS:A survey was distributed to all the members of the Study Group on Cutaneous Vascular Diseases and Skin Ulcers of the Italian Society of Dermatology and Venereology. The survey collected data on outpatient service organization, multidisciplinary involvement, nursing support, services provided, and patient volume. RESULTS:Thirty-nine clinicians from 10 centers participated. Nine centers reported dedicated outpatient dermatologic ulcer clinics, with approximately two thirds (6/9) integrating multidisciplinary approaches. The services operate an average of three days per week and manage approximately 13-14 patients per day (mean:13.5). Universally available services at ulcer outpatient clinics include dermatological consultation, wound care (curettage, simple dressings, advanced dressings) and specialized nursing staff. Further widely performed diagnostic and therapeutic procedures include microbiological swabs, skin biopsy and vascular consultation. More advanced services are available only in selected centers. CONCLUSIONS:This study highlights significant variations in the organization and resources of outpatient ulcer clinics among participating centers. Addressing these disparities through standardized protocols, equitable resource allocation, and integration of advanced tools is essential to improve patient care and outcomes.

BACKGROUND:Dermoscopy is a critical tool for diagnosing basal cell carcinoma (BCC) and differentiating its histopathological subtypes. However, BCC on the lower limbs may present with atypical dermoscopic features, making its diagnosis challenging. OBJECTIVES:To identify specific dermoscopic patterns of BCC on the lower limbs, focusing on the newly observed purpura-like pattern, and to assess how these features differ from BCCs in other anatomical sites. METHODS:A retrospective, single-centre study reviewed standardized polarized dermoscopic images of 478 BCCs collected between January 2011 and December 2022. Two independent dermatologists evaluated the dermoscopic images, blinded to histopathological diagnoses and anatomical sites. Statistical analysis was performed to determine correlations between dermoscopic features and BCC locations. A matched test set with dermoscopic images of skin conditions of the lower limb (control group) was then evaluated. RESULTS:A new dermoscopic pattern, a purpura-like pattern, was identified in lower-limb BCCs, in addition to other features such as dotted-glomerular vessels, shiny-white structures and small erosions. The purpura-like pattern, which appeared as peripheral, out-of-focus dots or globules on a coppery red background, was significantly associated with lower-limb BCCs (odds ratio 7.13, 95% confidence interval 5.01-10.16, P < 0.001). Dotted-glomerular vessels were also more frequent in lower-limb BCCs. In the control group, composed of 239 histologically confirmed non-BCC lower-limb lesions, the purpura-like pattern was identified in 3.8% (9/239) of lesions, including Kaposi sarcoma, acroangiodermatitis/stasis dermatitis, mycosis fungoides, viral wart and basosquamous carcinoma. Interrater agreement for pattern recognition was high (Cohen's kappa = 0.81, P < 0.001). CONCLUSIONS:The purpura-like pattern is an additional dermoscopic feature significantly associated with BCC on the lower limbs. Although not exclusive to BCCs, its presence, especially if combined with other dermoscopic criteria, may enhance diagnostic accuracy in this diagnostically challenging anatomical site. Further validation in larger, prospective studies is warranted.

Introduction: Skin cancer prevention campaigns aim to reduce modifiable risk factors, yet high-risk groups often maintain inadequate protection practices. Objectives: This study analyzed data from Italy's 2023 "Save Your Skin" campaign, which provided free skin checks nationwide. Methods: Data from 1,773 participants across 29 centers in 13 regions were collected to assess sun exposure, photoprotection habits, and skin cancer awareness, identifying gaps in prevention efforts. Results: Most participants were female (70.16%) with a median age of 36, and 96.61% were born in Italy. While 71.24% joined for preventive reasons, others participated due to changes in a nevus (12.35%) or personal (2.31%) or family (7.33%) history of skin cancer. Self-assessments of nevi often did not align with dermatologists’ evaluations, but family and personal history reporting was more accurate. Participants showed confusion about nevi and melanoma: only 52.7% correctly identified nevi as benign, while 67.2% recognized melanoma as malignant. On average, participants answered 1.57 out of 3 knowledge questions correctly, with those having a family or personal history of skin cancer performing better. High-risk sun exposure behaviors were identified in 37.78% of participants. Older adults used sunscreen less frequently but relied more on hats and shade, while younger individuals reported less sun exposure at work. Notably, participants with actinic damage demonstrated lower awareness and provided fewer correct answers on photoprotection. Conclusions: These findings underscore the need for targeted public health strategies to improve education on skin cancer prevention, particularly among high-risk and older populations.

INTRODUCTION:Magnified dermoscopy (MD), or optical super-high magnification dermoscopy, is an emerging technique in dermatology. OBJECTIVES:The study aimed to evaluate the distribution of conventional dermoscopy, MD, and reflectance confocal microscopy (RCM) features in dermoscopically equivocal pigmented lesions and to estimate their diagnostic accuracy. METHODS:A retrospective analysis of conventional dermoscopic (20x), MD (400x), and RCM images of dermoscopically equivocal pigmented lesions, diagnosed as either nevi or melanoma, was performed. Distribution of features, sensitivity, and specificity for dermoscopy, MD, RCM, and a combination of these last two with conventional dermoscopy was estimated. RESULTS:A total of 74 nevi and 20 melanomas were included in the analysis. A positive correlation was observed between seven-point checklist in conventional dermoscopy and the diagnosis of melanoma. With MD, a significant correlation between dots, non-edged papillae, and melanoma was observed, but the technique did not have a significant impact on diagnostic accuracy as compared to traditional dermoscopy. On the other hand, RCM, alone or in combination with traditional dermoscopy, proved to increase diagnostic accuracy, in particular, specificity for melanoma diagnosis. CONCLUSIONS:RCM has a defined role in increasing diagnostic accuracy of doubtful dermoscopic lesions, while the role of MD in clinical practice has yet to be defined, and methodologic standardization as well as a revision of terminology is encouraged to improve the recognition of features.

BACKGROUND:The differential diagnosis of early nail unit melanoma can be challenging. OBJECTIVES:This retrospective cross-sectional study aimed to characterize the clinical and dermoscopic changes in a series of cases of longitudinal melanonychia that underwent clinical and dermoscopic sequential digital monitoring. METHODS:All patients were adults presenting with a single acquired pigmented nail band and were monitored over time. Histologic diagnosis served as the gold standard for cases where excision was performed. For non-excised cases, inclusion in the study required a minimum of 1 year of documented clinical and dermoscopic stability. Clinical and dermoscopic features were assessed at baseline and during the final follow-up visit. RESULTS:After a median follow-up of 17 months, 27 out of 62 lesions were excised. Among these, six cases (9.7%) were diagnosed as in situ melanomas, nine (14.5%) as nevi and 12 (19.4%) as lentigo or melanocytic hyperplasia. At baseline clinical evaluation, most of the bands, both benign and malignant, occupied less than one-third of the nail plate (62.5% and 50%, respectively). Comparing dermoscopic features between baseline and follow-up, granular pigmentation emerged in 33.3% of malignant nail bands but only in 3.6% of benign bands (p = 0.04). An increase in the number of colours was observed in 50% of in situ melanomas, compared with 8.9% of benign lesions (p = 0.02). Additionally, 83.3% of melanomas showed an increased intensity of pigmentation, a feature seen in only 14.3% of benign bands (p = 0.001). Limitations include the relatively small number of melanoma cases (n = 6), all cases were from pigment lesion clinics in Europe and involved only Caucasian patients. Lastly, only pigmented lesions were included, so no conclusions can be drawn regarding amelanotic subungual melanoma. CONCLUSIONS:In conclusion, digital dermoscopy follow-up of longitudinal melanonychia is a valuable management strategy in uncertain cases. The emergence of new colours, granular pigmentation or increased intensity of pigmentation during follow-up should prompt a biopsy to rule out malignancy.

BACKGROUND:Pigmented purpuric dermatoses (PPD) are a group of chronic, benign skin conditions with limited evidence-based data regarding their diagnosis and management. The aim of our work was to evaluate the clinical practices of dermatologists in managing PPD, focusing on patient presentation, treatment preferences, and the need for further diagnostic evaluations. METHODS:We utilized a survey-based design for the present study. The survey was distributed to the Study Group on Cutaneous Vascular Diseases and Skin Ulcers of the Italian Society of Dermatology and Venereology. The survey collected data on the number of patients evaluated weekly, the proportion of patients requesting treatment, preferred therapeutic approaches, and indications for additional diagnostic tests. RESULTS:Twenty-four clinicians from 11 centers participated. Respondents reported managing an average of 5 PPD cases per week, with treatment required in approximately 50% of cases, while the remainder were incidental findings during evaluations for other dermatological conditions. Skin moisturizers and topical corticosteroids (tCS) were universally recommended as first-line treatments. Additional therapies included zinc oxide cream, compression stockings, and flavonoid-based oral supplements. Further diagnostic workups, such as leg Doppler ultrasound, skin biopsy, and blood tests, were considered necessary only in selected patients based on clinical presentation and comorbidities. CONCLUSIONS:Moisturizers and tCS are the cornerstone of PPD treatment, supplemented by tailored therapies and diagnostic evaluations. These findings highlight the need for standardized, evidence-based guidelines to optimize the management of PPD.

Cutaneous squamous cell carcinoma (cSCC) is the second most common type of skin cancer globally, accounting for 20% to 50% of all skin cancers [...]

Background: In a recent prospective, multicenter, two-arm randomized controlled trial (RCT), we demonstrated that adjunctive reflectance confocal microscopy (RCM) in routine clinical practice provides clinical benefits, including safe melanoma detection and a 43.3% reduction in the number needed to excise (NNE). Methods: A cost-benefit analysis was conducted based on NNEs for standard care (5.3) and adjunctive RCM (3.0). Cost data were supplied by one center, applying a micro-costing approach from the hospital's perspective. Costs were calculated for dermatology exams, excisions, medications, histopathology, and follow-up. The outcomes were extrapolated to provincial and national settings to assess the economic benefits of RCM. Results: The cost per patient for standard care was 143.63, compared to 114.74 for adjunctive RCM. The cost per melanoma excised with standard care (NNE 5.3) was 904.87, almost twice the cost for RCM (458.96). Annual regional and national costs for standard care were 864,150.85 and 11,491,849.00, respectively, while RCM reduced these to 438,306.80 and 5,828,792.00. Estimated annual savings with adjunctive RCM were 425,844.05 regionally and 5,663,057.00 nationally. The cost-benefit ratio for RCM was 3.89, meaning that for every 1 spent on RCM, there is a benefit of 3.89. Conclusion: In real-world clinical practice, adjunctive RCM offers significant economic advantages at local, regional, and national levels while maintaining patient safety and reducing unnecessary surgical procedures.

BACKGROUND:Familial melanoma comprises approximately 10% of cutaneous melanomas. Individuals with pathogenic germline variants have a higher risk of developing multiple primary melanomas (MPMs) than individuals who lack these variants. However, differences in clinical, dermoscopic and reflectance confocal microscopy (RCM) features between variant carriers and noncarriers are not well established. OBJECTIVES:To compare the clinical, dermoscopic and RCM characteristics of patients with MPMs with or without the pathogenic germline variants associated with familial melanoma. METHODS:This retrospective study included 45 patients with MPMs who underwent Sanger sequencing and/or custom next-generation sequencing (NGS) panels between 2020 and 2023. Clinical, dermoscopic and RCM images were reviewed and compared between pathogenic germline variant-positive and pathogenic germline variant-negative groups. RESULTS:Pathogenic germline variants in moderate-risk to high-risk melanoma genes were found in 15 patients. Carriers were diagnosed at a younger age than noncarriers [mean (SD) 41.8 years (10.1) vs. 53.5 (10.4); P < 0.001], more frequently had a family history of melanoma (P = 0.02), had more melanomas arising from pre-existing naevi (P < 0.001) and less actinic damage (P = 0.05). CDKN2A carriers were younger [38.9 years (11.4) vs. 45.3 (7.8)] and had fewer melanomas [2.7 (1.3) vs. 4.1 (1.2); P = 0.05] than MITF or POT1 carriers. CDKN2A carriers had low (n = 5), medium (n = 1) or high (n = 2) naevus counts, while MITF carriers had medium (n = 1) to high (n = 4) counts. Dermoscopically, pathogenic germline variant carriers showed fewer regression structures (8.3% vs. 39.8%; P = 0.01). RCM findings indicated a nonsignificant trend toward more dendritic cell-type melanomas in noncarriers (33.9% vs. 19.4%). CONCLUSIONS:Patients with MPMs who carry pathogenic germline variants demonstrate distinct clinical and imaging profiles compared with patients who do not carry these variants. These findings support personalized surveillance of individuals at high risk of developing MPMs and the integration of genetic testing into melanoma management. Further studies with larger cohorts are needed to refine genotype-phenotype associations.

JAK inhibitors are used to treat various inflammatory skin diseases. However, systemic formulations are associated with an increased risk of major adverse events. Ruxolitinib 1.5% cream is a selective topical JAK1 and JAK2 inhibitor, which has recently been approved by EMA and MHRA for treating non-segmental vitiligo, while being FDA-approved for both vitiligo and atopic dermatitis. Recent literature has reported the off-label use of topical Ruxolitinib for several skin conditions, but data are mostly limited to single case reports and series and few prospective studies, with mixed results. We conducted a systematic review of the literature to investigate the potential efficacy of topical Ruxolitinib in various skin diseases in an off-label setting. The following keywords were used for searching the MEDLINE (Pubmed) and Scopus databases from inception to September 2024: "ruxolitinib cream and dermatology" and "topical ruxolitinib and dermatology". Reviews, articles not focusing on the main topic, books and book chapters, and articles with no English text were excluded. A total of 170 studies were screened, of which 112 fell within exclusion criteria and 58 were assessed for eligibility. Of these, 28 studies, published between 2012 and 2024, were selected. Ruxolitinib cream resulted in being used off-label mostly for treating lichenoid and granulomatous dermatoses, as well as alopecia areata. While for the former skin conditions, topical ruxolitinib proved to be effective and safe, results on efficacy in alopecia areata were controversial. Topical ruxolitinib might be a promising therapeutic option for lichenoid and granulomatous dermatoses. Noteworthily, despite the exciting results from the oral formulation, no consistent data were described for topical ruxolitinib in alopecia areata. Our review reported encouraging results for many inflammatory skin conditions that should be investigated in further studies.

BACKGROUND:Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor that usually presents as a pink nodule on sun-exposed skin in elderly patients. This study aimed to investigate the dermoscopic patterns of MCC and identify predictors that may help distinguish it from other benign or malignant tumors often included in its differential diagnosis. METHODS:This was a study announced via an online call on the International Dermoscopy Society website where we collected macroscopic and dermoscopic images of MCC and other tumors with similar clinical morphology that served as controls. Sixteen experts were asked to assess the images for the presence of preselected dermoscopic features. Univariable feature analysis, multivariable logistic regression analysis, and interrater reliability assessment were performed. RESULTS:In total, 402 cases were collected: 134 MCCs and 268 controls. Three hundred and ninety six images were included in the analysis after the exclusion of poor-quality photographs. Pink color was the most common feature in MCC (92.4%, 95% confidence interval [CI]: 1.17-5.7), followed by white color (58%, 95% CI: 0.62-1.51) and linear irregular vessels (43.5%, 95% CI: 0.61-1.47). Scale on the surface was documented in 33.6% of MCCs compared to 23.4% of controls (95% CI: 1.01-2.69). Multivariable logistic regression analysis identified two positive predictors of MCC, namely pink color and scale, and three negative predictors, namely ulceration, brown, and blue-gray pigmentation. CONCLUSION:MCC might mimic other benign or malignant lesions. In nonpigmented tumors dermoscopically characterized by pink color and scales, MCC should be prioritized among the differentials.

Negative pigment network (NPN) is a dermoscopic structure frequently associated with melanoma. Though commonly observed in Spitz naevi (SN) and Spitzoid melanoma (SM), its reflectance confocal microscopy (RCM) correlates have been primarily studied in non-Spitzoid melanocytic neoplasms. This study aimed to identify clinical, dermoscopic, and RCM features associated with dermoscopic NPN in Spitzoid neoplasms and explore its histopathological correlates. We retrospectively analysed clinical, dermoscopic, and RCM images from 128 histopathologically confirmed SN and SM cases diagnosed between 2014 and 2020. Lesions were grouped by presence or absence of dermoscopic NPN, and comparisons were made across clinical, dermoscopic, and RCM features. A subset of 20 cases underwent histopathologic correlation. Of the 128 cases, 96 (74%) were SN and 32 (26%) SM. NPN was present in 58 lesions (45%)-40 SN (42%) and 18 SM (56%). NPN was associated with lesion diameter ≥ 5 mm, presence of shiny white structures, dotted vessels, and inversely associated with diffuse blue-white veil. SMs showed higher frequencies of asymmetry, multicomponent patterns, and extensive NPN. RCM features previously linked to NPN-round or linear surface disruptions, bright suprabasal areas, and broadened interpapillary spaces-were seen in 87% of cases but did not correlate with diagnosis or dermoscopic NPN. Corresponding histologic features included keratin-filled dells, hypergranulosis, and broadened rete ridges or infundibula. RCM correlates of dermoscopic NPN are frequently observed in Spitzoid neoplasms, independent of visible dermoscopic NPN, suggesting perceptibility may depend on contrast within dermoscopic patterns.