Reflectance Confocal Microscopy and Dermoscopy for the Diagnosis of Solitary Hypopigmented Pink Lesions: A Narrative Review.

Diagnosing solitary pink skin lesions poses a significant challenge due to the scarcity of specific clinical and dermoscopic criteria. Several benign lesions, such as cherry angioma, clear cell acanthoma, dermal nevus, keloid, hypertrophic scar, and Spitz nevus, often exhibit similar clinical and dermoscopic features. This similarity extends to some malignant lesions, including basal cell carcinoma, actinic keratosis, and amelanotic melanoma, making differentiation difficult. Recent studies highlight the enhanced diagnostic accuracy of reflectance confocal microscopy (RCM), which offers increased sensitivity and specificity compared to dermoscopy alone for diagnosing skin cancer. This study aims to summarize the application of dermoscopy and RCM in distinguishing between benign and malignant pinkish-reddish skin lesions. The integration of RCM with traditional dermoscopic techniques improves the ability to accurately identify and differentiate these lesions. However, it is crucial to note that for any suspicious lesions, a final diagnosis must be confirmed through surgical excision and histopathological evaluation. This comprehensive approach ensures accurate diagnosis and appropriate treatment, highlighting the importance of combining advanced imaging techniques in clinical practice.

Melasma and reflectance confocal microscopy: from baseline to treatment monitoring.

Melasma is a frequent condition worldwide, and it represents one of the most challenging disorders to treat in cosmetic dermatology. One of the critical factors for treatment prognosis is the assessment of the depth and distribution of pigment within the hyperpigmented area. Nowadays, non-invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to estimate pigment distribution and depth within different skin layers. This article aims to provide a systematic review of RCM applications in melasma, providing terminology and investigating characteristics of melasma at baseline and after medical and laser treatment. Our results support the recognition of two main types of melasma, epidermal and mixed type, thanks to the role of RCM in highlighting the precise pigment depth location in the skin non-invasively. RCM treatment monitoring enables the objectification of pigment variations after treatment and the identification of prognostic factors for different treatment modalities. After the era of the application of RCM as a technique applied strictly to skin cancers, additional cosmetic applications are emerging, such as the application of melasma treatment monitoring.

Unraveling the Complex Nexus of Human Papillomavirus (HPV) in Extragenital Keratinocyte Skin Tumors: A Comprehensive Analysis of Bowen's Disease and In Situ Squamous-Cell Carcinoma.

This comprehensive study delves into the intricate landscape surrounding the role of human papillomavirus (HPV) in extragenital keratinocyte skin tumors, specifically exploring Bowen's disease (BD) and in situ squamous-cell carcinoma (iSCC). Through a multifaceted examination, this research study elucidates the nuanced interplay of HPV, gender dynamics, anatomical site variations, and potential implications for the etiopathogenesis of these malignancies.

A Dramatic Response to Second-Line Nivolumab and Ipilimumab in BRAF-V600-Mutated Metastatic Melanoma.

Introduction: Current treatment options for BRAF V600-mutated unresectable stage III/IV melanoma include anti-PD-1 monotherapy or combination with anti-CTLA-4 or anti-LAG-3 agents, BRAF/MEK inhibitors, and clinical trials. The strategy of combination immunotherapy with nivolumab and ipilimumab has shown promising results, achieving higher response rates, longer duration of response, improved progression-free survival, and enhanced overall survival. The optimal sequence of treatments remains a topic of interest, with preliminary data suggesting a greater effectiveness of immunotherapy as the first-line approach. Preclinical trials have indicated that the efficacy of this sequence may be due to the modification of the immune environment by BRAF kinase inhibitors, leading to immune escape by tumor cells and resistance to immune checkpoint inhibitors. Case Presentation: We present a case of a 72-year-old woman with high-burden metastatic melanoma who failed to respond to prior targeted therapy with BRAF/MEK inhibitors and exhibited a successful response to the second-line treatment with ipilimumab and nivolumab. We discuss the potential reasons for this positive outcome contributing to the current debate concerning treatment sequences, resistance mechanisms, and biomarkers predictive of response to immune checkpoint inhibitors in metastatic melanoma. Conclusion: We believe that in few years the therapeutic algorithms in BRAF V600-mutated unresectable stage III/IV melanoma will be more complex since they will define clearly the correct therapeutic sequences with the inclusion of new immune checkpoint inhibitor drugs and multiple predictive biomarkers of response to better select patients eligible to immunotherapy.

Treatment of locally advanced and metastatic basosquamous carcinoma, navigating among sonic hedgehog pathway inhibitors, immune checkpoint inhibitors, chemotherapy, and radiotherapy: A case series and literature review.

Locally advanced (laBSCs) and metastatic basosquamous carcinomas (mBSCs) represent a therapeutic challenge. By definition, these forms are not amenable to surgery or radiotherapy, but according to literature reports, sonic hedgehog pathway inhibitors (HHIs), anti-programmed death 1 receptor antibodies (anti-PD-1), and other treatment approaches involving chemotherapy, surgery, and radiotherapy have been used. This work features 5 real-life cases of advanced BSCs, treated at the Dermato-Oncology Unit of Trieste (Maggiore Hospital, University of Trieste). In addition, a review of the current treatment options reported in the literature for laBSC and mBSC is provided, collecting a total of 17 patients. According to these preliminary data, HHIs such as sonidegib and vismodegib could represent a safe and effective first line of treatment, while the anti-PD-1 cemiplimab may be useful as a second-line option. Chemotherapy and combined approaches involving surgery and radiotherapy have been also reported to be suitable in some patients.

Carbon-assisted Q-switched Nd: YAG laser and Microneedling Delivery of Botulinum Toxin: a prospective pilot study.

INTRODUCTION: Carbon-assisted Q-switched Nd:Yag laser treatment consists in applying a topical carbon suspension all over the face followed by irradiation with a Q-switched 1064 Nd:YAG laser. The delivery of multiple microdroplets of dilute Onabotulinum Toxin-A into the dermis, has been investigated as a tool for facial rejuvenation. The aim of this study is to assess the effectiveness of the combined treatment with botulinum toxin and carbon peel laser (performed with a standardized technique) in patients with seborrhea, dilated pores and wrinkles, and to demonstrate its benefits in improving the overall skin aspect. MATERIAL AND METHODS: Patients enrolled in this prospective pilot study were subjected to 3 sessions of the combined treatment carried out 3 months apart. To evaluate the improvement of skin texture, wrinkles, dilated pores and acne lesions, several scales have been used, namely Fitzpatrick Wrinkle Assessment Scale (FWAS), the Physician Global Aesthetic Improvement Scale (GAIS), a photographic scale for the pore assessment and the Investigator Global Assessment of Acne (IGA). Face Q was also administered to assess patients' satisfaction. The scores obtained were compared using a paired T-test. RESULTS: Twenty patients were recruited. Difference of pre and post-treatment scores of the FWAS, GAIS, IGA, Face Q and the photographic scale for the pore assessment were statistically significant (p < 0,05). CONCLUSIONS: This combined protocol could be considered as an useful tool to treat skin flaws affecting texture, microroughness and seborrhea and to reduce enlarged pore size and its versatility allows customized treatment with minimum discomfort in patients.

Efficacy of a multimodal approach of laser therapy for earlobe keloids management in dark population.

BACKGROUND: Patients with keloids are often younger than 30 years old and have darker skin. AIM: To evaluate the efficacy and safety of CO2 laser therapy in the management of earlobe and helix keloids in dark subjects. METHODS: A total of 21 dark patients (five men and 16 women) presented with the earlobe and ear helix keloids, with a mean age of 30.5 (±6.7) years and with phototype between III-VI, were enrolled. In order to improve their earlobe and helix keloids, all patients underwent a single session of CO2 laser therapy immediately followed by a pulsed Dye laser procedure. A single well-experienced doctor performed all treatment sessions and the response to treatment. Patients were followed-up for 6 months after termination of therapy. Clinical images were examined and collected: all patients were examined clinically and with Dermoscopy. RESULTS: The majority of the patients treated show complete remission of keloid lesions. Clinical photographs show a visible aesthetic improvement of several types of keloids in dark subjects. CONCLUSIONS: Our data demonstrate that this combined laser therapeutic protocol appears to be effective and well tolerated for the management of earlobe and helix keloids in dark subjects, with no high recurrence rate and avoiding the adverse effects and lengthy recovery time.

Spitz nevus and melanoma: evaluation with dermoscopy and reflectance confocal microscopy.

Introduction: Spitz nevi (SN) include a wide range of benign melanocytic nevi, which are controversial due to their morphologic resemblance to melanoma (MM). Aim: To describe dermoscopic and reflectance confocal microscopic (RCM) features of SN compared to MM and assess the RCM utility in the differential diagnosis. Material and methods: We performed a multicentre retrospective analysis of MM and SN evaluated with dermoscopy and reflectance confocal microscopy. Three RCM mosaics were obtained for each lesion. Nine dermoscopic and twenty-one microscopic features were assessed for each lesion. Results: A total of 26 lesions (15 SN and 11 MM) were included. Dermoscopically, most SN showed a "starburst" pattern. Asymmetry was marked in 8 MM. There were 6 dermoscopic features significantly more prevalent in MM than in SN. RCM showed that an atypical honeycomb pattern, atypical infiltration, and disarray of the epidermis were significant for MM. SN mostly revealed a typical honeycomb pattern. At the DEJ, most of SN had a meshwork pattern; MM revealed an atypical meshwork pattern. Atypical cells and sheet-like structures were observed in most MM. Conclusions: A combined approach using dermoscopy and RCM supports the differential diagnosis of SN and MM. Although our study showed some significant differences between SN and MM in RCM, further research on a larger group should be considered.

Novel Management of Granuloma Formation Secondary to Dermal Filler with Intralesional 1444 nm Nd:YAG Laser Technique.

Background: Dermal fillers for soft tissue for the treatment of face sagging, volume loss, and wrinkles have become popular among patients of all ages and ethnicities, and their use is becoming increasingly widespread. Aim: the goal of this study was to evaluate the effectiveness and safety of a micro-pulsed, 1444 nm Nd:YAG laser on dermal filler complications, in particular on granuloma management. Methods: A subcutaneous, 1444 nm Nd:YAG laser was used on five female patients (range age 52-68 years) with hyaluronic filler granulomas located on the face (two on the cheek area and three on the lips); three patients had self-injected the filler, buying it online. Before and after the therapy, the patients received a skin ultrasound to determine the form and location of the granulomas and to determine if there had been a full or partial resolution. During this study, all possible adverse effects at the treatment site were monitored. The 5-point Global Aesthetic Improvement Scale (GAIS) (0 point-no change; 1 point-25%, mild improvement; 2 points-50%, moderate improvement; 3 points-75%, good improvement; 4 points-100%, excellent improvement) was recorded at a 3-month follow-up. Results: good results were obtained in the treatment of filler granulomas with the intralesional 1444 nm laser, even if just a single treatment was performed (one intervention was effective for curing granulomas up to 5 mm in diameter). Three patients were satisfied with excellent improvement, and two patients experienced good improvement. The results are functional and aesthetically satisfying, as shown by photographic assessment. At the last follow-up, the granuloma had reduced or completely disappeared in all cases, and no infections, burns, scarring or fibrosis, episodes of severe bleeding, or other serious adverse effects had been reported. All subjects tolerated the post-treatment period well. Conclusions: Our findings showed that granuloma treatment with an intralesional 1444 nm Nd:YAG laser is a minimally invasive, easy, fast, efficient, and low-risk procedure.

Actinic Keratoses: A Prospective Pilot Study on a Novel Formulation of 4% 5-Fluorouracil Cream and a Review of Other Current Topical Treatment Options.

BACKGROUND: Actinic keratosis (AK) is one of the most common skin diseases, with a low risk of progression into invasive squamous cell carcinoma. We aim to assess efficacy and safety of a novel formulation of 5-Fluorouracil (5-FU) 4% with once daily application for the treatment of multiple AKs. METHODS: A pilot study was performed on 30 patients with a clinical and dermoscopic diagnosis of multiple AKs, enrolled between September 2021 and May 2022 at the Dermatology Departments of two Italian hospitals. Patients were treated with 5-FU 4% cream once daily for 30 consecutive days. The Actinic Keratosis Area and Severity Index (AKASI) was calculated before starting therapy, and at each follow-up, to assess objective clinical response. RESULTS: The cohort analyzed included 14 (47%) males and 16 (53%) females (mean age: 71 ± 12 years). A significant decrease in AKASI score at both 6 and 12 weeks (p < 0.0001) was observed. Only three patients (10%) discontinued therapy, and 13 patients (43%) did not report any adverse reactions; no unexpected adverse events were observed. CONCLUSIONS: In the setting of topical chemotherapy and immunotherapy, the new formulation of 5-FU 4% proved to be a highly effective treatment for AKs and field cancerization.

A group of three miRNAs can act as candidate circulating biomarkers in liquid biopsies from melanoma patients.

Background: Staging of melanoma and follow up after melanoma diagnosis aims at predicting risk and detecting progression or recurrence at early stage, respectively in order to timely start and/or change treatment. Tumor thickness according to Breslow, status of the sentinel node and value of the lactate dehydrogenase (LDH) are well-established prognostic markers for metastatic risk, but reliable biomarkers identifying early recurrence or candidates who may benefit best from medical treatment are still warranted. Liquid biopsy has emerged to be a suitable method for identifying biomarkers for early cancer diagnosis, prognosis, therapeutic response prediction, and patient follow-up. Liquid biopsy is a blood-based non-invasive procedure that allows analyzing circulating analytes, including extracellular vesicles. Methods: In this study we have explored the use of 7 miRNAs, namely hsa-miR-149-3p, hsa-miR-150-5p, hsa-miR-21-5p, hsa-miR-200c-3p, hsa-miR-134-5p, hsa-miR-144-3p and hsa-miR-221-3p in plasma exosomes to discriminate melanoma patients from controls without melanoma in a cohort of 92 individuals. Results and discussion: Our results showed that three out seven miRNAs, namely hsa-miR-200c-3p, hsa-miR-144-3p and hsa-miR-221-3p were differentially expressed in plasma-derived exosomes from melanoma patients and controls. Furthermore, the expression of the three miRNAs may be a promising ancillary tool as a melanoma biomarker, even for discriminating between nevi and melanoma.

Long Pulsed 1064 nm Nd:YAG Laser Treatment for Skin Laxity and Wrinkle Reduction: Evaluation of New Handpiece and "in Motion" Setting Technique-A Case Series Study.

Background: The fourth most common healthy skin phenomenon is aging. Objective: To assess the efficacy of Nd:YAG laser with a new handpiece for the treatment of wrinkles and skin laxity. Methods: A total of 30 patients underwent three laser sessions at 1-month intervals. The treated areas were cheek, perioral, periocular, and forehead. The visual analog scale, Global Aesthetic Improvement Scale (GAIS), and a photographic evaluation were performed before and at 3 months follow-up after the last treatment. Results: After three treatment sessions, an improvement of the patient's skin texture with a reduction of wrinkles was observed. The GAIS score was no change 3%, improved 37%, much improved 57%, and very much improved 3%. The average pain score was 2.6 ± 0.5. None of the adverse effects monitored was detected. Conclusions: Laser treatments stimulate collagen without causing epidermal damage, which results in less disability time and postoperative awkwardness.