Clear Cell Sarcoma (CCS) of soft tissue is a rare and highly malignant neoplasm primarily affecting young adults, often presenting in the deep soft tissues of the extremities. Despite morphological and immunophenotypic similarities to melanoma, CCS arises from connective tissues and is characterized by a distinct genetic hallmark: the EWSR1-ATF1 fusion resulting from t(12;22)(q13;q12) translocation. This genetic signature is absent in melanoma, making molecular diagnosis essential for accurate differentiation. Additionally, recent evidence highlights the utility of PRAME as an immunohistochemical marker to distinguish CCS from melanoma and other neoplasms. Clinically, CCS commonly involves tendons and aponeuroses, with metastatic potential leading to poor prognoses despite optimal local disease management. Histologically, CCS features lobular growth, spindle-to-epithelioid cells with clear cytoplasm, and low mitotic activity, often necessitating a multimodal diagnostic approach incorporating histopathology, immunohistochemistry, and molecular testing. Therapeutically, wide surgical excision remains the cornerstone for localized disease, with sentinel lymph node biopsy aiding in staging. Adjuvant radiotherapy is considered in select cases, while chemotherapy has limited efficacy in metastatic settings. Emerging treatments, including targeted therapies focusing on EWSR1-ATF1-driven pathways and immune checkpoint inhibitors, offer hope for improved outcomes. This review synthesizes current knowledge on CCS, emphasizing diagnostic challenges, the role of PRAME, and advancements in therapeutic strategies to enhance patient care.

Background: In recent decades, dermatological diagnostics have undergone a profound transformation, driven by the integration of new technologies alongside traditional methods. Classic techniques such as the Tzanck smear, potassium hydroxide (KOH) preparation, and Wood’s lamp examination remain fundamental in everyday clinical practice due to their simplicity, speed, and accessibility. At the same time, the development of non-invasive imaging technologies and the application of artificial intelligence (AI) have opened new frontiers in the early detection and monitoring of both neoplastic and inflammatory skin diseases. Methods: This review aims to provide a comprehensive overview of how conventional and emerging diagnostic tools can be integrated into dermatologic practice. Results: We examined a broad spectrum of diagnostic methods currently used in dermatology, ranging from traditional techniques to advanced approaches such as digital dermoscopy, reflectance confocal microscopy (RCM), optical coherence tomography (OCT), line-field confocal OCT (LC-OCT), 3D total body imaging systems with AI integration, mobile applications, electrical impedance spectroscopy (EIS), and multispectral imaging. Each method is discussed in terms of diagnostic accuracy, clinical applications, and potential limitations. While traditional methods continue to play a crucial role—especially in resource-limited settings or for immediate bedside decision-making—modern tools significantly enhance diagnostic precision. Dermoscopy and its digital evolution have improved the accuracy of melanoma and basal cell carcinoma detection. RCM and LC-OCT allow near-histological visualization of skin structures, reducing the need for invasive procedures. AI-powered platforms support lesion tracking and risk stratification, though their routine implementation requires further clinical validation and regulatory oversight. Tools like EIS and multispectral imaging may offer additional value in diagnostically challenging cases. An effective diagnostic approach in dermatology should rely on a thoughtful combination of methods, selected based on clinical suspicion and guided by Bayesian reasoning. Conclusions: Rather than replacing traditional tools, advanced technologies should complement them—optimizing diagnostic accuracy, improving patient outcomes, and supporting more individualized, evidence-based care.

Background/Objectives: Extramammary Paget’s disease (EMPD) is a rare cutaneous malignancy arising in areas rich in apocrine glands that poses diagnostic and therapeutic difficulties. Although surgery remains the standard of care, achieving clear margins is challenging and recurrence rates are high. This review explores the contribution of non-invasive imaging for diagnosis and monitoring, and evaluates conservative, non-surgical therapies as alternatives to radical surgery. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic review was conducted: eligible studies included interventional and observational research, as well as case series and reports, assessing non-invasive diagnostic methods or non-surgical treatments for EMPD. Data extraction and risk-of-bias evaluation were performed independently by multiple reviewers, and a narrative synthesis summarized therapeutic outcomes and diagnostic performance. Results: Of 808 identified records, 82 met the inclusion criteria: 66 focused on non-surgical therapies, 15 on diagnostic techniques, and one on both. Reflectance confocal microscopy (RCM) and photodynamic diagnosis (PDD) showed high concordance with histopathology, aiding both diagnosis and margin delineation. Among therapies, topical imiquimod and photodynamic therapy (PDT) demonstrated encouraging response rates, while radiotherapy, laser ablation, and systemic chemotherapy were less consistently reported. Evidence quality was limited by small cohorts, heterogeneous regimens, and variable follow-up. Conclusions: Non-invasive imaging enhances diagnostic accuracy and surgical planning, while non-surgical treatments—particularly imiquimod and PDT—offer viable alternatives in selected cases. Larger prospective studies are needed to establish standardized protocols and clarify long-term outcomes.

Introduction: Folliculitis decalvans (FD) is a rare scarring alopecia mainly affecting middle-aged men, characterized by recurring episodes of follicular pustules, crusts, erythema, tufted hairs, and scars. Objectives: This study investigates the effectiveness of reflectance confocal microscopy (RCM) compared to trichoscopy for diagnosing and monitoring FD. Methods: The study involved 24 Caucasian patients diagnosed with FD. Patients were examined using trichoscopy and reflectance confocal miscroscopy (RCM), with a focus on specific features like erythema and inflammatory cell distribution. A subgroup of 16 patients was followed up after 3 months of therapy. The reproducibility of RCM and trichoscopy was assessed using Cohen Kappa Test. Results: RCM and trichoscopy consistently detected features such as tufted hairs, pustules, and perifollicular fibrosis. However, RCM provided more detailed insights into inflammatory activity and types of fibrosis, often overlooked by trichoscopy. It showed a reduction in vessels and inflammatory cells, which trichoscopy failed to detect. The concordance between RCM evaluations was excellent, indicating high reproducibility. Conclusions: RCM is effective in diagnosing and monitoring FD, offering detailed insights into inflammation and fibrosis. It complements trichoscopy, especially in aspects where trichoscopy is limited, such as precise measurement of inflammation. The study suggests that combining RCM with trichoscopy could enhance the accuracy of diagnosis and monitoring of FD, leading to tailored therapeutic approaches. Further studies with larger sample sizes and longitudinal designs are recommended to confirm these findings.

Background/Objectives: The efficacy of topical therapies in dermatology is often limited by the barrier function of the stratum corneum, which restricts drug penetration. Iontophoresis is a non-invasive transdermal delivery technique that uses a low-intensity electrical current to enhance the transport of charged and polar molecules across the skin. It has emerged as a strategy to improve local drug bioavailability while minimizing systemic exposure. We systematically reviewed the clinical evidence on the efficacy, safety, and pharmacologic performance of iontophoresis-assisted topical drug delivery in dermatologic diseases. Methods: This systematic review followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251234877). PubMed, Embase, Web of Science, CENTRAL, and ClinicalTrials.gov were searched through 19 November 2025 without language restrictions. Records were screened against predefined eligibility criteria, and data were extracted on study design, participants, dermatologic indications, intervention/comparator, iontophoresis parameters, efficacy outcomes, and adverse events. The risk of bias was assessed using RoB 2 for randomized trials and the JBI checklist for non-randomized studies. Because of substantial clinical and methodological heterogeneity, the findings were synthesized narratively and no meta-analysis was performed. Results: Twenty-one studies published between 1990 and 2025 met the inclusion criteria, including 15 randomized and 6 non-randomized studies. Investigated conditions included psoriasis, eczema, melasma, post-inflammatory hyperpigmentation, herpes labialis, onychomycosis, chronic ulcers, systemic sclerosis-related digital ulcers, acne scarring, and actinic keratosis. Across studies, findings were mixed. The most consistent signals of benefit were observed in pigmentary disorders and infectious diseases, whereas results were more heterogeneous in inflammatory dermatoses and some studies did not show superiority over active comparators. Tolerability was generally favorable, with adverse events limited to mild, reversible local reactions such as erythema, tingling, burning, or transient irritation. No serious treatment-related adverse events were reported. Conclusions: Iontophoresis may represent a useful non-invasive delivery-enhancement strategy in selected dermatologic settings, particularly when topical efficacy is limited by anatomical or physicochemical barriers. However, heterogeneity in protocols, formulations, outcomes, and clinical indications limits direct comparison and does not support broad conclusions of efficacy across all dermatologic conditions. Larger, standardized trials are needed to clarify its therapeutic role, long-term efficacy, and indication-specific benefit.