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Sonidegib is a Hedgehog pathway inhibitor (HHIs) used as first-line systemic treatment for patients with advanced basal cell carcinoma (aBCC). Alopecia is reported as a frequent adverse event (AE), occurring in 49% of patients. Forty-five patients with aBCC were treated with sonidegib between December 2022 and December 2023; among them, 11/45 patients developed alopecia. Trichoscopic features included yellow dots, black dots, exclamation mark hairs, and broken hairs. Upon LC-OCT examination, yellow dots were seen as dilated follicular dark spaces containing malted nonhomogeneous material and outlined by bright collarets; black dots corresponded to normal-sized follicular ostia filled with bright, homogeneous material and cadaverized hair; exclamation mark hairs were short dark dysmorphic hairs with a different size of proximal and distal end and broken hairs were short dysmorphic hairs. LC-OCT may provide additional insights of early signs and clinical evolution of sonidegib-induced alopecia in patients with aBCC.

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.

Introduction: Basosquamous carcinoma is an uncommon subtype of basal cell carcinoma (BCC), characterized by aggressive local growth and metastatic potential, that mainly develops on the nose, perinasal area, and ears, representing 1.2–2.7% of all head-neck keratinocyte carcinomas. Although systemic therapy with hedgehog inhibitors (HHIs) represents the first-line medical treatment in advanced BCC, to date, no standard therapy for advanced basosquamous carcinoma has been established. Herein, we reported a case series of patients affected by locally advanced basosquamous carcinomas, who were treated with HHIs. Case Presentation: Data of 5 patients receiving HHIs for locally advanced basosquamous carcinomas were retrieved (2 women and 3 males, age range: 63–89 years, average age of 77 years). Skin lesions were located on the head-neck area; in particular, 4 tumors involved orbital and periorbital area and 1 tumor developed in the retro-auricular region. A clinical response was obtained in 3 out of 5 patients (2 partial responses and 1 complete response), while disease progression was observed in the remaining 2 patients. Hence, therapy was interrupted, switching to surgery or immunotherapy. Conclusion: Increasing evidence suggests considering HHIs for large skin tumors developing in functionally and cosmetically sensitive areas, in patients with multiple comorbidities, although their use for basosquamous carcinoma require more exploration, large cohort populations, and long follow-up assessment.

Background: Acral melanocytic lesions often pose a diagnostic and therapeutic challenge for many clinicians. Reflectance confocal microscopy (RCM) is an imaging technique widely used for the assessment of skin cancers. The aim of this review is to explore the applicability of RCM for the diagnosis of nevi and melanoma on the acral sites. Methods: Study selection was conducted based on the application of RCM for acral melanocytic lesions. All types of articles (original articles, short reports, and single case reports) were included in the analysis following PRISMA updated guidelines. Results: The search retrieved 18 papers according to the selection criteria; after removing duplicate records and additional articles by one or more of the exclusion criteria, a total of seven studies were carefully evaluated. Conclusions: RCM seems a valuable and useful additional tool for the diagnosis of acral melanocytic lesions, and its use may decrease the need for invasive procedures to some extent. Visualization of deeper layers may be achieved through mechanical removal of the superficial stratum corneum.

Background: Line-field confocal optical coherence tomography is a novel technology able to reproduce a “virtual biopsy” of the skin. The aim of this review is to explore the application of line-field confocal optical coherence tomography (LC-OCT) in various skin diseases, covering skin cancers, inflammatory and infectious skin diseases, genetic diseases, cosmetic procedures, and less common disorders. Methods: Study selection was conducted based on LC-OCT and using pertinent MeSh terms, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines from inception to March 2024; to evaluate the quality and risk of bias of studies, Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used. Results: the search retrieved 154 papers according to the selection criteria; after removing publications by one or more of the exclusion criteria, a total of 96 studies were found to be suitable for the analysis. Conclusions: Increasing evidence supports the use of LC-OCT as an adjunctive diagnostic tool for the in vivo diagnosis of a variety of skin tumors. As this device can be considered a “bridge” between dermoscopy and histopathology, widening applications in numerous fields of clinical dermatology, including inflammatory skin disease treatment, presurgical mapping, cosmetic procedures, and monitoring of non-invasive therapies, have been explored.

Introduction: Pigmentation of lip and/or genitalia is mainly due to the development of benign melanotic macules, with a less occurrence of melanocytic and other non-melanocytic lesions. Mucosal melanoma has worse prognosis compared with cutaneous counterpart, hence identification of atypical features for an early diagnosis is crucial. Objectives: The aim of this study was to report further data of confocal features characterizing pigmented mucosal lesions of genital area and of the lips and test the diagnostic role of the reflectance confocal microscopy (RCM)lip score. Methods: Clinical, dermoscopic and RCM images of histologically proven pigmented lesions, involving the genital area (vulva or glans penis) and lip, were retrospectively reviewed. RCM images were evaluated for malignant criteria, and statistical analysis was conducted for categorical variables. Results: Seventy pigmented lesions were included in the study and divided into two groups based on the body area location: lip (17) and genital area (53). Architectural disarray (P = 0.002), dendritic (P = 0.031) and roundish cells in epidermis (P < 0.0001), interpapillary dendritic cells (P = 0.039) and junctional atypical cells (P = 0.002) were associated to genital melanoma. Melanoma involving the lip was characterized by roundish cells in epidermis, a criterion found in one labial benign lesion, only (P = 0.005). Main limitations of the study are the inclusion of low melanomas and the presence of epidermal dendritic cells in melanosis and melanoma, as a confusing factor in imaging. Conclusions: Dermatologists should consider confocal microscopy as an adjunctive tool to dermoscopy in the differential diagnosis of pigmented mucosal lesions, especially in presence of clinical and dermoscopic findings suspicious for malignancy.

Background: Periocular malignancies may be clinically different from the examples arising at other sites, with possible delayed diagnosis and greater challenges for treatment and repair. Line-field confocal optical coherence tomography (LC-OCT) is a recently developed technique characterized by an unprecedented capacity to acquire high-definition images in vertical and horizontal modes. In this study, we aimed to investigate the LC-OCT morphological features of a series of eyelid skin lesions, correlating them to histopathological findings. Methods: Patients with biopsy-proven equivocal skin lesion in the eyelid area, previously investigated by means of LC-OCT, were included in the study. Percentage overall agreement was estimated for LC-OCT and histopathological diagnosis for study cases. Results: A total of 51 patients (28 women, 23 men; mean age 66.4 years old), for a total of 51 skin lesions, were assessed. The histopathological diagnosis consisted of 30 malignant and 21 benign tumors. Different entities were characterized by peculiar findings in LC-OCT, alike to histopathological features, allowing for an accurate “in vivo” classification in almost all cases, with a diagnostic concordance with histopathology of 92.1% (47/51). Conclusions: By integrating this new imaging technique into the assessment of suspicious tumors in this area, diagnostic accuracy may increase, improving strategies adopted in multidisciplinary meetings and patient-centered care.

While in the past technology has mostly been utilized to store information about the structural configuration of proteins and molecules for research and medical purposes, Artificial Intelligence is nowadays able to learn from the existing data how to predict and model properties and interactions, revealing important knowledge about complex biological processes, such as aging. Modern technologies, moreover, can rely on a broader set of information, including those derived from the next-generation sequencing (e.g., proteomics, lipidomics, and other omics), to understand the interactions between human body and the external environment. This is especially relevant as external factors have been shown to have a key role in aging. As the field of computational systems biology keeps improving and new biomarkers of aging are being developed, artificial intelligence promises to become a major ally of aging research.

Introduction: A peripheral rim of globules represents a marker of horizontal growth phase in nevi and is a common feature in children and adolescents. The observation of melanocytic lesion with peripheral globules (MLPG) in adulthood deserve more attention, since a melanoma may exhibits this feature albeit rarely. Risk stratified management recommendations considering a global clinical approach are still missing. Objectives: To analyze current knowledge on MLPG and propose an integrated management algorithm stratified for age groups. Methods: We conducted a narrative review of current published data on MPLG, analyzing clinical dermoscopic and confocal distinguishing features of melanoma from bening nevi. Results: The risk of finding a melanoma when removing a MLPG increases with age especially in people >55 years old and results significantly higher on extremities, head/neck and in case of a single asymmetrical lesion, ≥6 mm in diameter. Dermoscopic features associated to melanoma diagnosis include atypical peripheral globules, asymmetrical distribution, multiple rims as well as globules reappearance after previous loss. In addition, wide blue-grey regression areas, atypical network, eccentric blotches, tan structureless peripheral areas and vascularizationare atypical dermoscopic features. Confocal worrisome findingss are represented by pagetoid cells within the epidermis, architectural disarrangement and atypical cells of the dermo-epidermal junction with irregular peripheral nests. Conclusion: We proposed a multi-step age-stratified management algorithm integrating clinical, dermoscopic and confocal findings that may increase the early recognition of melanoma and avoid surgical excision of benign nevi.

Immune checkpoint inhibitors have shown efficacy in the treatment of different cancers by stimulating the antitumoral activity of the patient’s immune system, representing a major breakthrough in the field of cancer therapy. Monoclonal antibodies including anti-cytotoxic T-lymphocyte–associated protein 4, anti–programmed cell death protein 1 and its ligand inhibitors have been approved for advanced melanoma among other solid cancers. Although immunotherapy demonstrated a good safety profile, a new spectrum of multisystemic immune-related adverse events has been recently reported due to their use. Cutaneous reactions represent one of the leading adverse events, often reported in literature as “skin rash”, and rarely further characterized in distinct dermatologic entities. Herein we describe the distinctive cutaneous rashes occurring during immunotherapies for advanced melanoma, discussing implications in the treatment management.

Limited data concerning the development of autoimmune skin diseases after COVID-19 vaccination are currently available. Recently, a few reports described the development, worsening or recurrence of alopecia areata after the administration of COVID-19 vaccines. High variability in terms of disease onset following vaccination as well as the heterogeneous topical and/or systemic treatment approaches have been described. Methods: All patient-related data and images were obtained as part of clinical routine. Diagnosis of alopecia areata was established according to clinical and trichoscopic findings, along with the exclusion of common differential diagnoses. Results. Twenty-four patients, 20 females (83.3%) and four males (16.7%), with a mean age of 39.1 years (age range: 14–66 years), were examined for the occurrence of alopecia areata within 16 weeks after COVID-19 vaccination. Out of 24, 14 patients (58.3%) experienced a patchy alopecia areata, while an extensive disease occurred in 10/24 patients (41.7%): six patients with whole scalp involvement (alopecia areata totalis) and four patients with the whole body affected (alopecia areata universalis). Twelve patients reported a history of autoimmune disease (50%). Treatment with topical corticosteroid was performed in almost all patients with patchy alopecia areata, whilst it was associated with systemic drugs (corticosteroids, minoxidil, cyclosporin) in the case of generalized alopecia areata and alopecia areata universalis. Mean baseline values of Severity of Alopecia Tool (SALT) score decreased from 43.4 to 36.6 after 12 weeks of treatment, with evidence of hair regrowth in 16/21 patients. Conclusion. This study described the occurrence of alopecia areata after COVID-19 vaccination and its management that implicates the use of both topical and systemic therapies.