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.

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.

Locally advanced basal cell carcinoma: Real-life data with sonidegib.

In recent years, the category of hedgehog pathway inhibitor (HHI) has shown great results in patients with advanced basal cell carcinoma (aBCC), but few real-life data on efficacy and safety profile of sonidegib are available. We report our management of locally advanced BCCs (laBCCs) with sonidegib, also describing the favorable response of locally advanced basosquamous carcinomas (laBSCs) treated with this hedgehog signaling inhibitor. Sonidegib was generally well tolerated and it achieved high response rates, improving quality of life. Our single-center experience could be useful to better delineate long-term efficacy and tolerability profile demonstrated in the trials described in literature. Moreover, our cases provide preliminary evidence that sonidegib might be effective for laBSC.

Melasma treatment: a systematic review.

Melasma is a common chronic refractory disorder of pigmentation affecting people with darker skin types. Overall prevalence varies between 8.8% and 40%, depending on the ethnicity of the population and the geographical area. Therapeutic management of melasma is challenging, with high recurrence rates which significant impacts on the quality of life. No single treatment is universally efficacious. Systemic treatments with tranexamic acid and polypodium leucotmatous had promising results, although the former was related to systemic side effects. Microneedling and peeling were also efficacious, although their superiority to topical hydroquinone, the gold standard in melasma treatment, remains to be established. Similarly, laser and light devices have been beneficial. However, recurrence rates remain high in all treatment groups. Combination therapies, either in double or triple combinations yielded the best results when compared to single terapies. Treatment choice should be made after Wood's lamp examination, as well as dermatoscopic evaluation, in order to select the best treatment option, targeted at each melasma subtype.

Regression of nevi, vitiligo-like depigmentation and halo phenomenon may indicate response to immunotherapy and targeted therapy in melanoma.

We present two patients with stage IV melanoma, the first with BRAF wild-type melanoma with multiple visceral metastases treated with immunotherapy (pembrolizumab) and the second with BRAFV600E melanoma with subcutaneous and lymph nodes metastasis treated with BRAF and MEK-inhibitors (dabrafenib/trametinib). Already after the second cycle of immunotherapy, the first patient developed a diffuse regression of nevi, perceptible only with the use of dermoscopy and 3 months later a clinically evident poliosis of the eyebrows. The second patient, treated with dabrafenib/trametinib, developed small areas of leukoderma on his chest and white halos around nevi with a dermoscopic globular or structureless pattern. Both observations are suggestive for an immune reaction against melanocytic cells, which is further supported by the complete response to systemic therapy in both patients. It has been demonstrated that the development of vitiligo-like depigmentation during immunotherapy is associated with a better prognosis; in our patient, the phenomenon of poliosis appeared much later than the dermoscopic presence of regression among his nevi, suggesting that the latter may be an early sign (along with vitiligo-like phenomena) of good response to immunotherapy. On the other hand, the development of halo nevi and leukoderma during treatment with BRAF/MEK-inhibitors, suggests that not only immunotherapy but also targeted therapy may induce an immunologic response against melanoma and nevi, again indicative of a favorable prognosis. More data are needed to confirm these findings; however, they indicate that dermatologists should be involved in the follow-up of patients with melanoma, both in studies and clinical practice.

Basal cell carcinoma and dermal nevi of the face: comparison of localization and dermatoscopic features.

BACKGROUND: Basal cell carcinoma (BCC) and dermal nevi located on the face can easily be confused on clinical examination. Little is known about the different preferential localizations of these entities, and a systematic analysis of dermatoscopic features for differential diagnosis is lacking. METHODS: Clinical and dermatoscopic images of BCCs and dermal nevi were retrospectively evaluated to study their relation to various face anatomical areas, BCC histotype, classic and nonclassic dermatoscopic BCC criteria, as well as typical dermatoscopic criteria for dermal nevi. RESULTS: We examined 118 BCCs and 77 dermal nevi, all having histopathological confirmation. BCCs were most frequently located on the lateral side of the forehead (12.7%), nasal dorsum (10.2%) and nasal ala (9.3%), while dermal nevi were found predominantly on the buccal area (11.8%), scalp (11.8%), and perioral region (10.8%). The prevalent dermatoscopic criteria for BCC were the classic arborizing vessels (94.1%) and arborizing microvessels (89%). The most common BCC histotype on the face was sclerodermiform (47.5%), followed by nodular (28%) and superficial (24.6%). CONCLUSIONS: This study shows that BCCs are preferentially located on the lateral side of the forehead, nasal dorsum and nasal ala, while dermal nevi of the face are preponderantly located on the buccal area, scalp, and perioral region. The dermatoscopic features confirmed the frequency of classic and nonclassic criteria for BCCs already demonstrated in other studies. No significant site-specific features were observed for either BCCs or dermal nevi.

In vivo reflectance confocal microscopy of halo nevi.

INTRODUCTION: Halo nevi named also Sutton's nevi are uncommon melanocytic lesions occurring especially among adolescents. There are two effective diagnostic methods: dermoscopy and in vivo reflectance confocal microscopy (RCM), which can help us to observe many structural elements and characteristic features of Sutton's nevi. OBJECTIVES: The aim of this study was to describe reflectance confocal microscopy features of halo nevi. METHODS: Eleven patients with fourteen halo nevi were examined by FotoFinder Medicam 800 dermoscope and reflectance confocal microscope Viva Scope 1500 between May of 2018 and September of 2019. RESULTS: Dermoscopic examination revealed 78.6% nevi with a globular pattern, while 21.4% showed a homogenous pattern. In RCM, a typical honeycombed pattern was observed in 57.1% of nevi. 42.9% of nevi showed a disarray of the epidermis and presence of dendritic cells. 35.7% of all lesions presented roundish atypical cells in the epidermis. Roundish pagetoid cells in the dermo-epidermal junction were detected in 14.2% of nevi. Non-edged papillae were observed in 50% of lesions. In each nevus, there were dilated vessels. 50% of nevi revealed dense nests in the periphery, although in case of one lesion the dishomogeneous nests were observed. CONCLUSIONS: Halo nevi are important "melanoma simulators" in confocal microscopy.

Neoadjuvant Therapy for Non-melanoma Skin Cancer: Updated Therapeutic Approaches for Basal, Squamous, and Merkel Cell Carcinoma.

OPINION STATEMENT: Recently introduced systemic therapies for locally advanced and metastatic non-melanoma skin cancers (NMSCs) are paving the way for neoadjuvant approach. Although none of the therapeutic options has currently gained indication in this setting, neoadjuvant approach for NMSCs is an open field and we are likely to see huge developments in the near future. Targeted therapy with sonic hedgehog pathway inhibitors is very effective in locally advanced or multiple basal cell carcinomas while immunotherapy with immune checkpoint inhibitors appears to be promising for advanced cutaneous squamous cell carcinoma and Merkel cell carcinoma. To date, targeted therapy and immunotherapy represent the frontiers in NMSC therapeutic management and, according to recent studies, good results can be achieved.

Melanoma diagnosed on digital dermoscopy monitoring: A side-by-side image comparison is needed to improve early detection.

BACKGROUND: Digital dermoscopy monitoring (DDM) helps to recognize melanomas lacking specific dermoscopic features at baseline, but the number of melanomas eventually developing specific features is still unknown. OBJECTIVE: To assess how many melanomas are identified because they develop melanoma-specific criteria over time compared with melanomas recognized by side-by-side image comparison. METHODS: A case-control study was conducted collecting 206 melanomas: 103 melanomas diagnosed during DDM follow-up and 103 melanomas diagnosed at baseline. The control group was composed of 309 benign lesions consisting of 103 nevi excised for diagnostic reasons, 103 not excised nevi, and 103 not excised seborrheic keratoses. Dermoscopic images of all 515 lesions were randomly presented to 2 blinded experts to give a diagnosis and to score the criteria of the 7-point checklist. RESULTS: Of the 103 melanomas diagnosed at baseline, 78.6% (n = 81) were correctly identified compared with only 40.8% (n = 42) of melanomas diagnosed after DDM (P < .001). Of the 103 melanomas excised after DDM, 59.2% (n = 61), did not develop melanoma-specific criteria and were identified only because of the side-by-side image comparison. LIMITATIONS: The type of morphologic changes considered as suspicious on DDM was not assessed. CONCLUSIONS: Most melanomas are diagnosed with DDM by side-by-side image comparison.

Effects of topical piroxicam and sun filters in actinic keratosis evolution and field cancerization: a two-center, assessor-blinded, clinical, confocal microscopy and dermoscopy evaluation trial.

Background: Actinic keratosis (AK) is considered an "in situ" non-melanoma skin cancer induced by ultraviolet chronic exposure. Sunscreen and topical anti-inflammatory agents like diclofenac could improve the evolution of this kind of lesions. A topical product containing piroxicam 0.8% and sun filters (50 SPF) (ACTX) has been shown to be very effective in reducing AK lesions. So far, no data are available regarding the effects of this product on skin modifications evaluated by reflectance confocal microscopy (RCM) and dermoscopy at the lesion sites and on the skin around the lesions (field cancerization). Study aim: To evaluate in a two-center, assessor-blinded, prospective trial the effect of ACTX on AK number, RCM and dermoscopy parameter evolution of a target lesion in subjects with multiple AK lesions. Subjects and methods: A total of 54 subjects (42 men and 12 women; mean age 65 years) with AK lesions grade I-III located on the scalp (n = 36) or face (n = 18) were enrolled after their written informed consent. ACTX was applied twice daily on the face and scalp for six consecutive months. AK lesion count was performed at baseline and after 3 and 6 months. Lesion count was assessed in a blind fashion evaluating digital color high definition images performed at each visit and coded in a blinded fashion. RCM evaluations were performed at the same time-points. A dermoscopy evaluation was performed at baseline and after 6 months. RCM and dermoscopy were assessed on a pre-specified target lesion. The RCM severity score was used evaluating 11 items, examining stratum corneum, stratum granulosum, stratum spinous and dermal layers (maximum score 11 points). The dermoscopy score evaluated erythema, scaling and follicular plugs (from 0 to 4 for each item) and pigmentation (from 0 to 5). Results: Forty-nine subjects (90%) concluded the trial. At baseline, the mean (SD) number of AK lesions was 9.6 (5.2). AK lesions significantly decreased to 5.9 and to 5.6 after 3 and 6 months of ACTX treatment (p = .001; intention to treat analysis), representing a -42% reduction. A reduction of AK lesion numbers >50% in comparison with baseline was observed in 51% of subjects at month 6. New AK lesions appeared in five subjects (9%). The RCM mean (SD) severity score at baseline was 6.4 (2.0). ACTX treatment was associated with a progressive and significant (p = .002) reduction to 4.9 after 3 months and to 4.8 (2.3) at month 6 (a -25% reduction). The dermoscopy score at baseline was 5.5 (2) and it was reduced significantly (p = .007) to 4.5 (2) at the end of the study. The product was in general very well tolerated. Conclusion: A 6 month application of ACTX in subjects with AK lesions was associated with an improvement in AK lesion count and with a reduction in the RCM/dermoscopy severity scores of the target lesion. Trial registration number: ISRCTN22070974.

Plasma radiofrequency ablation for treatment of benign skin lesions: Clinical and reflectance confocal microscopy outcomes.

BACKGROUND: In the latest few years, plasma radiofrequency ablation has turned out a good option for treatment of several benign skin lesions. The technique can be easily performed to treat skin lesions with limited tissue invasion and no residual scars or hypo/hyperpigmentation areas. OBJECTIVE: The aim of this study was to assess the effects of plasma radiofrequency ablation in treatment of benign skin lesions, through clinical and reflectance confocal microscopy outcomes. METHODS: Six patients who presented benign skin lesions underwent long-wave plasma radiofrequency ablation treatment with DAS medical device (Technolux, Italia). Reflectance confocal microscopy analysis was performed at baseline and after 1 month. RESULTS: The treatment was well tolerated; only a slight erythema and a thin crust on the treated area were referred for 3-7 days after treatment. After one month from treatments, we observed the complete disappearance of the lesions and no significant signs of inflammation, redness, hypo/hyperpigmentation, or scars on the site of the treated areas; these clinical data were also confirmed by reflectance confocal microscopy analysis. CONCLUSIONS: Long-wave plasma radiofrequency ablation actually can be considered a well-tolerated, painless, safe, effective, and low-cost procedure for skin treatments.

The use of in vivo reflectance confocal microscopy for the diagnosis of melanoma.

INTRODUCTION: The use of reflectance confocal microscopy (RCM) for imaging the skin non-invasively raised constantly during the last decade. One of the main field of application is skin cancer diagnosis, and in particular melanoma diagnosis. Several studies have investigated the diagnostic accuracy of RCM as compared to dermoscopic examination, and its value in enhancing early diagnosis of dermoscopic difficult melanomas. Areas covered: The purpose of this paper was to review the principles behind RCM image acquisition as well as to describe and discuss key RCM features of melanoma. Moreover, we conducted a literature search in order to highlight the current available evidence about RCM sensitivity and specificity in the diagnosis of melanoma. Expert commentary: During the last decade, we assisted at the increasing interest in non invasive imaging tools for the diagnosis of skin cancer. RCM is one of the most studied of a series of diagnostic methods that are emerging in the field of melanoma imaging. Most probably in the future, RCM will be more frequently available in tertiary referral centres, thus the knowledge of the pros and contra of the tool and its clinical applicability is of upmost importance in order to allow correct referrals with the final aim of improving diagnostic accuracy.