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AIM: Literature data have suggested an increase of incidental thyroid nodules in patients with malignancies, including melanoma. METHODS: The ultrasound findings of 168 consecutive melanoma patients were revisited in order to evaluate the presence of incidental thyroid nodules and the results were compared with clinical features, Breslow thickness and the rate of malignancy of incidental thyroid nodules. RESULTS: We observed that: 1) incidental thyroid nodules are more frequent in patients affected by melanoma (60.6%) than in the healthy population; 2) no statistically significant difference were found in thyroid involvement on the basis of gender and age; 3) incidental thyroid nodules frequency is increased in patients with thinner melanoma and this increase is more evident if we consider melanoma in situ and female patients; 4) it was not detected malignant incidental thyroid nodules. CONCLUSION: The data revealed a high frequency of incidental thyroid nodules in patients with melanoma, suggesting that it is necessary to study this association in a larger group of patients, also including age/gender matched controls.

Background: Scalp melanomas are usually thicker and show worse prognosis than other sites and other head and neck melanomas. One hypothesis to explain this aggressive behavior could be diagnosis delay attributed to hair concealment of lesions. Methods: Primary melanomas of the scalp diagnosed over two decades at four reference centers in Australia and Italy were included. Hair coverage and visibility of the lesions were assessed on preoperative photographic documentation by two investigators and correlated with some prognostic factors (Breslow thickness, mitotic rate, and ulceration). Patients records and pathology reports provided clinical and histological data. Results: The majority of 113 melanomas included were located on easily visible areas of the scalp – hairless scalp (49%) or hairline (15%). The remaining ones (36%), considered to be hair-covered, showed more frequently thinning of hair (63%) than a dense hair coverage (37%). Melanomas of “hairy scalps” were more frequently invasive (81%) and had higher median Breslow (0.8±1.3mm) than those arising on bald scalps or areas with thinning of hair (43%; 0±0.6mm), P=0.004. However, when considering only the invasive cases (n=55), Breslow thickness and mitotic rate were not statistically different between concealed and easily visible areas. Melanomas detected by a doctor were thinner than those first noticed by the patient, relatives, or a hairdresser (P&nbsp

Background: Advanced cutaneous squamous cell carcinoma (aCSCC) represents an area of unmet clinical need, with no standardized treatments until the recent approval of immune checkpoint inhibitors (ICIs). Objectives: The aim of the study was to describe clinical characteristics and therapeutic strategies of a real-life Italian cohort of aCSCC patients managed at the beginning of cemiplimab approval as compassionate use in Italy. Methods: A multicenter retrospective study was performed by 10 Italian centers in the period January 1, 2018–May 31, 2020. Patients aged ≥18 years and diagnosed with aCSCC (locally aCSCC and metastatic CSCC) were eligible for the study. Analysis of patients’ characteristics and treatment strategies was performed. Results: 239 patients were initially recruited in the study: 19 patients were excluded due to incomplete data collection, yielding a final cohort of 220 patients, of which 191 and 220 were included for patients’ clinical characteristics and therapeutic intervention analysis, respectively. Median age at the time of diagnosis was 81 years (range: 72–86); nodal metastases were detected in 64/220 (29%) patients, and distant metastatic spread was reported in 33/220 (15%) patients. Most of our patients referred chronic occupational and/or recreational sun exposure, experienced ≥1 sunburn during their lifetime, never wore hats or used photoprotective filters, and presented with signs of cumulative sun damage (solar lentigines and/or actinic keratosis). Majority of our cohort received at least one intervention directed to the primary tumor (n = 212, 96.3%); surgery and radiotherapy were the most common therapeutic choices. Immunotherapy was administered to a small number of patients as compassionate use, especially in the metastatic setting. Conclusions: Our study outlines the complex and heterogeneous clinical and therapeutic landscape of aCSCC patients at the beginning of ICI era, highlighting the need of a standardized care for this fragile and high-need patient population.

Summary Background A number of mutations related to malignant melanoma (MM) have been identified, and of the mutated genes, BRAF has been found to be altered in > 50% of cases. Most of these have been BRAF V600E mutations, whereas the incidence of BRAF V600K may vary from 10% to 30%. Little is known about the clinical prognostic correlations of BRAF V600K MMs. We evaluated the clinical and dermoscopic features, incidence, therapy response and outcomes in the medium to long term. Aim To compare the clinical and dermoscopic characteristics, the response to systemic therapies and the prognosis among MMs with BRAF V600E and BRAF V600K mutations. Methods We retrieved the data of patients tested in our centre for MM from 2012 to 2015, including clinical features, dermoscopic pictures, clinical history and tumour mutations. Only patients with BRAF V600E and BRAF V600K mutations were included. Any MMs positive for BRAF V600K mutation were collected, and the number of V600K cases and their features were used to extract the same number of patients with BRAF V600E from our database using a matching method. The clinical and dermoscopic presentation, therapy response and disease progression of the two groups were then evaluated. Results In total, 132 cases of BRAF V600E-mutated MMs were identified, and then randomized with a propensity-score method to match the 10 retrieved cases of BRAF V600K mutation. Both groups had a nodular appearance to the tumours and an advanced disease stage, and no significant differences in dermoscopic features were highlighted. During the follow-up period, four patients with BRAF V600K died of disease-specific causes. Moreover, we found a higher frequency of metastasis, a faster disease progression and more rapid mortality in patients with BRAF V600K. Conclusion Despite the small size of this study, the results show similar clinical and dermoscopic characteristics between V600E and V600K mutations, but compared with BRAF V600E MMs, BRAF V600K MMs seem to be less responsive to therapy and have a worse prognosis.

Introduction: Skin cancer is the most common type of cancer and is classified in melanoma and non-melanoma cancers, which include basal cell, squamous cell, and Merkel cell carcinoma. Specific microRNAs are dysregulated in each skin cancer type. MicroRNAs act as oncogene or tumor suppressor gene regulators and are actively released from tumor cells in the circulation. Cell-free microRNAs serve many, and possibly yet unexplored, functional roles, but their presence and abundance in the blood has been investigated as disease biomarker. Indeed, specific microRNAs can be isolated and quantified in the blood, usually in serum or plasma fractions, where they are uncommonly stable. MicroRNA levels reflect underlying conditions and have been associated with skin cancer presence, stage, evolution, or therapy efficacy. Areas covered: In this review, we summarize the state of the art on circulating microRNAs detectable in skin cancer patients including all the studies that performed microRNA identification and quantification in the circulation using appropriate sample size and statistics and providing detailed methodology, with a specific focus on diagnostic and prognostic biomarkers. Expert Opinion: Circulating microRNAs display a relevant biomarker potential. We expect the development of methodological guidelines and standardized protocols for circulating miRNA quantification in clinical settings.

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We report the case of a young woman who developed metastatic melanoma in the inguinal nodal region, which acquired chondrosarcomatous differentiation and preserved the BRAF mutation found in the primary tumor. The patient was treated with a BRAF/MEK inhibitor combination therapy (dabrafenib/trametinib), which was demonstrated to be effective and well‐tolerated., BRAF‐mutated melanoma with chondrosarcomatoid differentiation and response to targeted therapy.

Background: Lymphovascular invasion (LVI) is considered an unfavorable prognostic factor in cutaneous melanoma (CM). However, its detection by hematoxylin and eosin (H&E) is challenging, with discordant data about its association with clinical-pathological features and no previous studies investigating the inter- (IrOA) and intra-observer (IaOA) agreement. Herein, we tested H&E and double staining (DS) for CD34/SOX10 to detect the LVI in a cohort of 92 CMs, evaluating the IrOA, the IaOA, and the association with the other clinical-pathological features. Methods: Five authors independently evaluated 92 consecutive and retrospectively enrolled cases of CMs. We assessed the IrOA (Fleiss's Kappa/FK and intraclass correlation coefficient/ICC) and the IaOA (Cohen's Kappa/CK) with both H&E and CD34/SOX10. Furthermore, we compared the LVI assessment with the two stains and analyzed the association with other clinical-pathological features [χ2 tests for dichotomous and categorical data; Student t-test (normal distribution) and Mann-Whitney U-test (non-normal distribution) for continuous data]. Results: The IrOA was almost identical with H&E (FK=0.446; ICC=0.805) and CD34/SOX10 (FK=0.454; ICC=0.810); by contrast, the IaOA was higher with H&E for one pathologist (CK: 0.809) and with CD34/SOX10 for the other one (CK: 0.563). Applying previously defined criteria, LVI was detected in 10 (9.2%) and 11 (10.1%) cases with H&E and CD34/SOX10, respectively (p = 1.000). Both H&E and CD34/SOX10 were significantly associated with vertical growth phase (H&E, p: 0.014; CD34/SOX10, p: 0.010), mitosis ≥ 1/mm2 (H&E, p: 0.000; CD34/SOX10, p: 0.004), pT (H&E, p: 0.000; CD34/SOX10, p: 0.001), Breslow thickness (H&E, p: 0.000; CD34/SOX10, p: 0.001), and lymph node and/or distant metastasis (H&E, p: 0.005; CD34/SOX10, p: 0.000); only H&E was associated with ulceration (p: 0.002) and distant metastasis (p: 0.000), conversely, only CD34/SOX10 was associated with lymph node metastasis (p: 0.003). Conclusions: CD34/SOX10 does not improve the IrOA and the IaOA of the LVI assessment in CM; furthermore, H&E and CD34/SOX10 show a similar profile of association with the other unfavorable clinical-pathological features of CM. As result, CD34/SOX10 could be a redundant diagnostic tool if applied for the prognostic characterization of not-selected CM in a routine diagnostic scenario.

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Background: The diagnosis of nodal nevi (NN) is challenging as they mimic melanoma metastases (MM), with a detection rate mostly ranging between 1% and 11% in sentinel lymph node biopsy (SLNB). Herein, we assessed the incidence of NN and the association with the clinical-pathological features of primary melanoma, adopting the updated European Organisation for Research and Treatment of Cancer (EORTC) protocol for SLNB. Methods: All cases of paired melanoma and SLNB were retrospectively evaluated (April 2019-May 2020). Appropriate statistical tests were adopted, with significant variables included in the logistic regression model. Results: 81 patients and a total of 186 lymph nodes (LNs) were included. Eleven patients had only NN and 4 had both NN and MM (18.5%); 29 LNs (15.6%) showed at least one NN and 12 (6.5%) showed more than one NN (a total amount of 43 NN was detected). All NN and none MM stained for p16. NN were associated with age < 60 years (p: 0.042), no ulceration (p: 0.025) and nevus-associated melanoma (NAM) (p: 0.018), with this latter being the only predictor at the logistic regression model (p: 0.022). Conclusions: The updated EORTC protocol shows a high number of NN and highlights a strong association with NAM.

Background: Retinoids and alpha-hydroxy acids are commonly used topically as anti-aging substances. Current medical devices contain retinoic acid (0.02%) and glycolic acid (4%) in a polyvinyl gel vehicle (R-G gel). There are still no clinical data nor objective evaluation of the anti-aging effect this product has in the short term. Aims: To assess in a prospective 1-month, noncomparative, primary outcome assessor-blinded proof-of-concept trial the clinical efficacy, tolerability, and the skin cells modification (evaluated through reflectance confocal microscopy; RCM), of R-G gel in skin aging treatment. Methods: Twelve women with moderate-severe skin aging (Glogau score≥3) were enrolled. The product was applied on the face three times a week for 4weeks. Study visits were performed at baseline and after 2 and 4weeks. RCM evaluation was performed openly at each visit using Viva Scope 1500 to evaluate the left cheek (5mm below the zygomatic process). Results: Eleven subjects concluded the trial. At baseline, the Glogau score was 3.4±0.5 and decreased significantly at week 4 (P=.0001; ANOVA test) to 2.7±0.6. Significant reductions of dark spots (−40%) and severity of wrinkles (−12%) were observed at week 4 compared to baseline. The RCM score improved significantly at week 4 with the recovery of the polygonal keratinocytes pattern as the central aspect observed. Conclusion: The gel containing retinoic acid and glycolic acid showed significant improvements of the clinical signs of severe skin aging with a concomitant improvement of epidermal and dermal structures evaluated via RCM.

Orale und Nagelpigmentierungen: eine für den Kliniker nützliche Parallelität.

Squamous cell carcinoma (SCC) is the most common malignancy of the nail unit. Pathogenetic mechanisms are yet to be determined, and a deeper molecular characterization of this disease is still necessary. The aim was to obtain a molecular characterization of NU SCC samples using an NGS approach to identify the genetic drivers involved in this tumor. The presence of HPV infection was also assessed. Furthermore, the mutational status was correlated with specific clinical-pathological features for a better insight into the carcinogenesis of this uncommon tumor. We analysed twenty paraffin-embedded nail unit SCC samples from patients diagnosed with primary SCC of the nail unit by next genome sequencing. In the 20 tested samples, the neoplastic cells enrichment ranged from 10% to 50% (mean value: 25.7%). In 14/20 cases (70.0%), at least one mutation was detected; whereas in the other six cases (30.0%), no alterations were observed (‘wild-type/WT cases’). Overall, a total of 23 mutations were identified in the 20 specimens. TP53 was the most mutated gene (6/20 cases, 30.0%), while cKit, GNAS, EGFR, DICER1 and CTNNB1 were observed in one sample each (5.0%). No clinical-pathological parameters (age, sex, depth of invasion-DOI, histological subtype, grading and HPV) were significantly associated with the mutational status. The nail unit SCC mutational landscape appeared to be heterogeneous, favouring the hypothesis of a complex pathogenesis and an interaction of multiple elements, including HPV infections. This wealth of information undoubtedly improves our understanding of SCC biology.

We report the case of a 64-year-old north-Italian female who accessed our dermatological emergency room for the appearance of sudden multiple red dots all over his body. She referred that the rash started five days ago, three-four hours after receiving the SARS-CoV-2 mRNA vaccine second dose (Pfizer, Cominarty). She did not report any additional symptoms, The past medical history is almost silent, except for ulcerative colitis controlled without medications. She has not taken drugs in chronic nor in a discontinuous manner in the last two months.

Polypoid melanoma is a variant of nodular melanoma, whose poor prognosis depends on its thickness and the presence of ulceration at the time of diagnosis. The authors report two cases of polypoid melanoma, presenting as broad, cauliflower-like, polypoid masses. Dermoscopy was characterized by a multicolored pattern, atypical polymorphic vessels, and the fiber sign. Clinical and dermoscopic features can help to diagnose polypoid melanoma and exclude other possible differential diagnoses. However, histology remains mandatory to confirm the diagnostic suspicion.

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Objectives: The extension of atypical melanocytes to the hair follicle, also termed melanoma folliculotropism, is poorly evaluated and its role is contradictory. We performed an observational study focusing on anatomical areas rich in follicles, such as the head and neck region. Methods: Primary head and neck melanomas diagnosed in the Melanoma Unit, Policlinic Sant'Orsola-Malpighi, University of Bologna were analyzed. Folliculotropism was evaluated with a quantitative and morphologic parameter. Statistical analyses were performed correlating patients' prognosis with folliculotropism and other clinical and histopathologic factors. Results: The study was carried out on a sample of 62 patients. The diffuse distribution (atypical melanocytes present in more than three contiguous follicular units) correlated with scalp localization, nodular subtype, higher Breslow thickness, and a poorer prognosis. Conclusions: We believe that folliculotropism should be further investigated and reported by pathologists during the histologic diagnosis of melanoma.

Skin cancers are the most common cancers worldwide. They can be classified in melanoma and non-melanoma skin cancer (NMSC), the latter includes squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and merkel cell carcinoma (MCC). In recent years, the crucial role of non-coding RNAs (ncRNAs) in skin cancer pathogenesis has become increasingly evident. NcRNAs are functional RNA molecules that lack any protein-coding activity. These ncRNAs are classified based on their length: small, medium-size, and long ncRNAs. Among the most studied ncRNAs there are microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNA (circRNAs). ncRNAs have the ability to regulate gene expression at transcriptional and post-transcriptional levels and are involved in skin cancer cell proliferation, angiogenesis, invasion, and metastasis. Many ncRNAs exhibit tissue- or cell-specific expression while others have been correlated to tumor staging, drug resistance, and prognosis. For these reasons, ncRNAs have both a diagnostic and prognostic significance in skin cancers. Our review summarizes the functional role of ncRNAs in skin cancers and their potential clinical application as biomarkers.

Acral lentiginous melanoma (ALM) is the most common type of malignant melanoma (MM) in Asians, Afro-Americans and Middle-Easterners. It represents 1.5-10% of all MM cases, being the most common histological type of MM arising on palms, soles and nail apparatus, which is more generically defined as acral MM. To date no risk factors have been officially established, however a history of trauma may be involved in the pathogenesis of acral MM. This shows heterogeneous clinical features and frequently presents with advanced stage and aggressive behavior, often as a result of misdiagnosis or delayed identification. Dermoscopy is helpful for an early diagnosis of ALM: the most characteristic dermoscopic patterns are the parallel ridge and the irregular diffuse pigmentation. On histopathology ALM displays a lentiginous growth pattern, with melanocytes arranged as solitary units along the basilar epidermis, without notable pagetoid growth in the early stage. Not all acral MMs present a lentiginous pattern: superficial spreading melanoma and nodular melanoma patterns are also possible. Novel studies investigating the biologic characteristics of acral MM reported variable results: the overall mutational rates ranged respectively between 8.5% and 23% for KIT, between 3.6% and 33.3% for BRAF and between 3% and 47% for NRAS in ALMs. Increasing attention has been recently given to other genes, such as telomerase reverse transcriptase, platelet-derived growth factor receptor alfa and cyclin D1. Larger molecular investigations urge to describe the molecular profile of acral MM, to allow the development of specific targeted therapies.

Mohs micrographic surgery (MMS) is a good treatment option for epithelial neoplasms, especially when localized in areas where tissue conservation is crucial, such as the nail unit (NU). MMS is a method of radical excision offering high cure rates due to the margin control and functional preservation. Our aim is to provide a review on the use of MMS for the treatment of the most common nail tumours. We revised the current literature on the use of MMS to treat malignant neoplasms (Bowen's disease, squamous cell carcinoma, melanoma, basal cell carcinoma, keratoacanthoma, carcinoma cuniculatum) and benign neoplasms (onychomatricoma and glomus tumour). MMS represents a successful surgical option for nail tumours, firstly in terms of tissue conservation: the NU anatomy is complex and the preservation of the component structures is imperative for its functionality. Secondly, due to the surgical radicality, which is essential not only for the clearing of malignant tumours, but also for benign cases, in order to reduce recurrences. Although a conservative treatment of NU melanoma with MMS has been proposed, in our experience, the conservative approach with functional surgery is a good option for the treatment of non-invasive melanoma (in situ and Ia).

Immunotherapy with checkpoint inhibitors significantly improves the outcome for stage III and IV melanoma. Cutaneous adverse events during treatment are often reported. We herein aim to review the principal pigmentation changes induced by immune check-point inhibitors: the appearance of vitiligo, the Sutton phenomenon, melanosis and hair and nail toxicities.

none 10 no Oral pigmentations (OPs) are often neglected, although a meticulous examination of the oral cavity is important not only in the diagnosis of oral melanoma, but also for the detection of important clinical findings that may indicate the presence of a systemic disease. OPs may be classified into two major groups on the basis of their clinical appearance: focal and diffuse pigmentations, even though this distinction may not appear so limpid in some cases. The former include amalgam tattoo, melanocytic nevi, melanoacanthoma and melanosis, while the latter include physiological/racial pigmentations, smoker's melanosis, drug-induced hyperpigmentations, postinflammatory hyperpigmentations and OPs associated with systemic diseases. We will discuss the most frequent OPs and the differential diagnosis with oral mucosal melanoma (OMM), underlining the most frequent lesions that need to undergo a bioptic examination and lesions that could be proposed for a sequential follow-up. none Lambertini, M; Patrizi, A; Fanti, P A; Melotti, B; Caliceti, U; Magnoni, C; Misciali, C; Baraldi, C; Ravaioli, G M; Dika, E Lambertini, M; Patrizi, A; Fanti, P A; Melotti, B; Caliceti, U; Magnoni, C; Misciali, C; Baraldi, C; Ravaioli, G M; Dika, E

The effect of hormonal stimulation and fertility treatments, on the development of malignant melanoma (MM) remains to be determined. The aim of this study was to investigate the presence of oestrogen receptor alpha (ERα) and progesterone receptor (PR) in MM and nevi after hormonal stimulation. Immunohistochemical analyses were performed utilizing antibodies specifically directed against ERα and PR in MM and atypical nevi specimens from patients: (1) diagnosed during pregnancy, (2) diagnosed in the six months following delivery, or (3) who had undergone repetitive cycles of hormonal stimulation for in vitro fertilization (IVF) in the year that preceded MM diagnosis. Controls were atypical nevi and MM specimens of female patients of the same age group who had received no hormonal therapies and reported no pregnancies in the five years before diagnosis. Twenty-eight female patients at childbearing age were selected for this study. Strong cytoplasmic positivity of ERα and PR was detected in atypical melanocytes of two MM specimens of patients who had undergone repetitive cycles of hormonal stimulation during IVF procedures. All other specimens showed no expression of ERα or PR. Since our results represent preliminary findings, conclusions regarding a possible correlation between IVF therapy and melanoma occurrence cannot be ascertained. Larger laboratory studies should be performed to investigate reproductive hormone receptor expression in MM in women following IVF, pregnancy, prolonged contraceptive use, or hormone replacement therapy.

We report hereby a Median canaliform nail dystrophy of Heller in a patient with atopic dermatitis: ‘miraculous’ healing with dupilumab

Vulvar intraepithelial neoplasia (VIN) is a subtype of in situ squamous cell carcinoma (SCC). The diagnosis is clinical and histopathological. Dermoscopy of VIN has been scarcely reported. Herein we describe the dermoscopic features in 4 female patients. This article is protected by copyright. All rights reserved.

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Background The association of clinical and dermoscopic features with BRAF mutational status has been poorly analysed in multiple primary melanomas (MPM). Objective To investigate whether concordance of BRAF mutational status is associated with dermoscopic similarity in multiple melanomas of the same patient. Methods Dermoscopic images and corresponding tissue sections of 124 melanomas from 62 patients with MPM were selected at four Italian Dermatology Departments. Similarity of dermoscopic appearance between multiple melanomas was evaluated according to the presence of the same prevalent dermoscopic feature. The BRAFV600 mutational status was analysed with allele-specific TaqManTM assays or pyrosequencing. Spearman's correlation and univariate and multivariate regression analysis were used for statistical analysis. Results A similar dermoscopic appearance was identified in 38.7% (24/62) of patients with MPM and was correlated with older age at first diagnosis (rho: 0.26; P: 0.042) and occurrence on sun-damaged skin (rho: 0.27; P: 0.037). The BRAFV600 mutation was detected in 39.5% (49/124) of the tumors and a concordant BRAF mutational status between melanomas in 33/62 (53.2%) MPM patients. Dermoscopically similar melanomas showed 5.7-fold higher odds to be concordant for BRAF mutational status compared to dissimilar lesions (OR: 5.7; 95% CI 1.7-19.5; P: 0.005). Conclusion Dermoscopic similarity of multiple melanomas represents an independent clinical predictor of a concordant BRAF mutational status in MPM patients.

We read with interest the paper by Longo C. etal.1 regarding the diagnostic accuracy of ex vivo fluorescence confocal microscopy (FCM) for Mohs surgery (MMS) of basal cell carcinomas and we appreciated the potential of this imaging tool. Nevertheless, we would like to point out some issues regarding the use of MMS reported in the case series. As showed in picture 2, standard vertical sections were cut and stained according to the "perimeter technique" (PT) in contrast with the principles of MMS consisting in cutting horizontal sections in order to get a proper peripheral and margin control. This article is protected by copyright. All rights reserved.

The correlation between HPV and nail squamous cell carcinoma is investigated in a case series.

Background Skin biopsy is an important tool for various skin conditions. However, in the case of leg ulcers, some Authors still consider it highly risky and mandatory only in selected cases. Methods The aim of this study was to evaluate the rate of adverse events after leg ulcers biopsy in 866 consecutive patients referring to our Wound Care Unit in Bologna from January 2008 to December 2016. Two biopsies were performed (from the border and the centre) by the same dermatologist following a standardized structured protocol. Results A total of 329 males and 537 females (ratio of 1:1.6), mean age 72 years (range 50-97 years) underwent a skin biopsy. Up to 70% of all analyses revealed a vascular ulcer (614 patients; 70.9%) while other conditions (252 patients; 29.1%) included inflammatory dermatitis, vasculitis, ulcerated neoplasms, infective lesions, post-traumatic and pressure sores, erosive pustular, dermatitis and pyoderma gangrenosum. Adverse events occurred in 322 patients (38.43% of all biopsies), mostly a dull pain (320 patients, 37%) that resolved within some hours. Five patients with vasculitis (0.6%) experienced a worsening of the lesion and another five patients (0.6%) developed erysipelas. Only two patients, on double antithrombotic therapy (0.23%), had intraoperative bleeding. No allergic reactions were detected. Conclusions According to our experience, skin biopsy should be mandatory for non-healing wounds. It is safe and involves only a low rate of adverse events.

Chilblain lupus erythematosus is a rare, chronic variant of cutaneous lupus erythematosus that occurs during cold or damp periods on the hands, fingers, or feet. It is often associated with other forms of cutaneous lupus and about 20% of patients develop systemic lupus erythematosus. Various medications have been put forward, including steroids, mycophenolate mofetil, calcium channel blockers, and hydroxychloroquine, but the symptoms do not remit completely.

Spitzoid neoplasms may represent a difficult diagnosis in the practice of dermatopathology. We evaluated the concordance of the fluorescence in-situ hybridization (FISH) assay, histopathology, and dermoscopy in a group of adults and in a group of children with spitzoid neoplasms. The FISH assay, designed to detect the copy number of the RREB1 (6p25), MYB (6q23), and CCND1 (11q13) genes and of centromere 6 (Cep 6), was performed in a group of children and in a group of adults with a histopathologic diagnosis of spitzoid neoplasms. FISH data were compared with dermoscopy and histopathology. Fifteen spitzoid neoplasms were collected from 13 patients (five children and eight adults): nine lesions were histologically diagnosed as typical Spitz nevi; three lesions were melanomas and three were atypical Spitz nevi. The conventional FISH criteria were concordant with the clinical and histopathologic diagnosis of Spitz nevi in four adults and in three children. FISH criteria of the other neoplasms showed a concordance with the histopathologic diagnosis in three cases. Discordant results were obtained in five cases (two children, three adults). The FISH melanoma assay proved more reliable in spitzoid lesions found in adults than in children. This assay should be interpreted carefully in pediatric patients with Spitz nevi in the context of histological features as melanomas in the pediatric population may show distinct chromosomal aberrations.

The observation of a black-brown pigmentation of the nail is often alarming for the patient and for the clinician, as they are aware that it can be a possible clinical manifestation of melanoma of the nail apparatus. Luckily, however, nail melanoma is a much less frequent cause of brown-black nail color than other melanocytic and nonmelanocytic pigmentations, which include subungual hematoma, exogenous pigmentations, and melanonychia due to benign conditions. A correct clinical history and careful examination help the clinician to distinguish the different conditions and to decide the correct management of melanonychia both in children and in adults.

BACKGROUND: Targeted therapies in melanoma have shown clinical benefit in incrementing the overall survival of metastatic patients. However, cutaneous adverse events have been frequently associated with these drugs. METHODS: We report our experience in the management of patients treated with dabrafenib for metastatic melanoma, focusing on the monitoring of pigmented lesions. Dermatologic evaluation was performed during the first visit, at the start of each treatment and subsequently after every four weeks. Global nevi count, videodermoscopy of suspected lesions, and surgical excisions when necessary were performed at the beginning of the treatment and every fourth week. All other cutaneous adverse events (cAEs) were noted and documented. Eleven patients were included. RESULTS: The most important cAEs included palmo-plantar hyperkeratosis, diffuse xerosis and pigmented lesion changes. Regarding the latter, in 6 patients, especially in the first months of treatment, we observed hyperpigmentation and hyperkeratosis of the nevi, of the pigmented mucosae and, in one patient, hyperkeratotic changes on a cutaneous metastasis. Histopathology of the excised lesions showed one ex novo melanoma occurrence and benign changes to pre-existing nevi. CONCLUSIONS: The awareness of the importance of sequential monitoring of pigmented lesions, with particular attention to the lesions of new onset, is crucial for the best management of these complex patients.

Abstract Context: Cutaneous toxicity is a frequent side effect of new anticancer targeted therapies. Skin reactions can severely impact the patient's physical, psychological and social well-being and may sometimes lead to discontinuations either treatment dose reductions. Objective: This study evaluates the impact of cutaneous adverse drug reactions (cADR) of the new therapies bortezomib and lenalidomide and presents a review of their skin side effects. Materials and method: Type, frequency, severity, time of onset and management of cADR were collected and the medical records of all multiple myeloma patients receiving bortezomib or lenalidomide in the Hematology and Medical Oncology Institute of the University of Bologna, were analyzed. Results: A total of 17 cADR occurred in 10 patients of 17 (58.8% of patients) treated with bortezomib: 5 rashes, 3 events of pruriginous rash, 1 purpuric rash, 2 records of mouth swelling, 1 stomatitis-mucositis, 3 cases of edema in the lower limbs, 1 patient referred pruritus and another telogen effluvium. Eight skin manifestations were due to lenalidomide in 7 patients of 25 treated (28%): 2 pruriginous rashes, 3 cases of edema, 2 records of pruritus, 1 case of stomatitis-mucositis. Three adverse events linked to bortezomib and 4 to lenalidomide forced to a complete withdrawal of the drug, while 3 reactions due to bortezomib mandated a dose reduction. Dermatological evaluation was performed only in 2 patients treated with bortezomib and 1 with lenalidomide. Discussion: Evaluations of cADR due to bortezomib and lenalidomide were performed. There are no other reports focused on skin events in patients treated with the triple regimen velcade (bortezomib)-thalidomide-dexamethasone (VTD) up to date. Our study suggests that cutaneous toxicities, when researched by Dermatologists, are a side effect even more frequent than the reported data. Limitations: As it is a single institute and retrospective study, ongoing cADR were rarely evaluated by dermatologists; thus, it is possible that cutaneous reactions (especially mild) may have been under reported by Hematologists and Oncologists in clinical records. Conclusions: Even with the development of new drugs for cancer treatment, "old" cutaneous side effects may still be present, compromising patients' quality of life. Physicians prescribing bortezomib and lenalidomide should monitor their patients for the spectrum of cADR, and they should involve dermatologists in consultations and management of these events. A multidisciplinar approach is necessary to oncologic patient in order to provide a tailored supportive clinical care.

Summary Background Subungual squamous cell carcinoma (SSCC) is the most common malignancy of the nail unit. Mohs micrographic surgery (MMS) is a microscopically controlled surgical technique that has a high cure rate for skin cancers despite allowing narrow surgical margins. Objective To evaluate the long-term effectiveness of MMS in the treatment of SSCC, and in particular its ability to reduce the number of digital amputations. Methods Fifteen patients diagnosed with SSCC were treated with MMS as the first-line surgical approach, and were followed up for between 2 and 5 years. Results SSCC was completely excised in 13 patients, while two patients required amputation of the distal phalanx. For tumours with predominantly exophytic growth, clinical and radiological findings were found not to be reliable indicators of bone invasion. No recurrences were detected on follow-up. Conclusion Our results show that MMS provides a high cure rate for SSCC and reduces the number of amputations needed. MMS should become the first-line surgical approach for SSCC.

Background Pain is a frequent symptom in cancer patients. The aim of our study was to evaluate the presence of pain in histopathologically-diagnosed hypertrophic actinic keratosis (AK) or cutaneous squamous cell carcinoma (SCC). Methods An observational study evaluating pain presence and intensity in skin cancer was performed, including patients affected either by SCC or by hypertrophic AK. Pain intensity was assessed using the 11-point Numeric Rating Scale, ranging from 0 (absence of pain) to 10 (most intense pain). Both spontaneous pain and pressure-related pain intensity, due to local digital pressure, were evaluated. Results In patients with SCC, spontaneous pain was present in 57.5% of the cases, while pressure-related pain was revealed in 80.0% of the cases. In hypertrophic AK patients, spontaneous pain was detected only in 15.0% of the cases, while pressure-related pain was present in 25.0% of the cases. A statistically significant difference between the 2 groups was found in the evaluation of spontaneous and pressure-related pain values, these values being significantly higher in the SCC group. No significant correlations between the degree of inflammation, the histotype or invasiveness of SCCs, and the intensity of pain were found. Conclusions The recognition of pain as a symptom, more frequently associated with SCC, might prove useful in the clinical practice. Further research is needed, in order to better understand and characterize pain associated with different skin neoplasms.

BACKGROUND: Several options for the treatment of ingrowing toenails are available, ranging from simple conservative approaches to extensive surgical procedures. OBJECTIVE: To evaluate in a long-term follow-up (36 months) the efficacy of chemical matricectomy with phenol for the treatment of ingrowing toenails. METHODS AND MATERIALS: A total of 197 phenol ablations were performed in 139 patients with stage 2 and 3 disease. Each patient was examined weekly until full wound healing was achieved and was followed for 36 months to assess the long-term efficacy of the treatment. The healing period after surgery ranged from 2 to 4 weeks; few postoperative complications were seen. RESULTS: Only three recurrences were observed (after 2, 4, and 11 months). Short-term results were excellent. No severe complications occurred during the 36-month follow-up period. Cosmetic results were remarkable. The success rate was 98.5%. CONCLUSIONS: Phenol cauterization is an excellent surgical method for the treatment of ingrowing toenails, being simple and associated with low morbidity and a high success rate, even over the long term (36 months).

Background/purpose: If the occlusion time of a closed chamber evaporimeter on the skin is too long, saturation might occur. We previously compared an open chamber and a closed chamber device on healthy volunteers. Comparable data on stripped skin with higher evaporation rates are not available. This study compares the sensitivity and correlation of open and closed chamber devices in a tape-stripping human model. The amount of tape removed SC was also quantified with a protein assay method. Methods: Ten healthy volunteers (six male and four female; seven Caucasians and three Asian; mean age 38±16) were enrolled. In a randomized manner, one forearm was measured by an open chamber device and the opposite by a closed chamber device. After recording baseline measurements, 20 strippings were taken on each test site with tape disks. Transepidermal water loss (TEWL) was measured at the end of 10 and 20 tape strippings at each test site. Stratum corneum (SC) aggregates in the strips was assayed. Results: The mean values obtained from two devices were similar after 10 trips and 20 strips. There was no statistically significant difference. The closed chamber device showed a slightly higher (but not significant) inter-individual coefficient of variation. SC aggregates in the strips were similar and without a statistically significant difference. Conclusion: The study suggests that both devices might yield similar TEWL values on stripped human skin in vivo.

Background: Syphilitic alopecia (SA) is mainly described in single case reports, and there are only a few epidemiological studies. Objective: To investigate the clinical and dermoscopic features of SA in patients with secondary syphilis and to record its actual prevalence. Methods: All patients with a diagnosis of secondary syphilis were clinically and trichoscopically evaluated in search of hair and scalp alterations. Results: Five of 12 patients (41.6%) diagnosed with secondary syphilis had SA. The ‘moth-eaten' pattern was detected in 4 patients (80% of cases): 1 had ‘essential' SA, whereas 3 patients had ‘symptomatic' SA. The ‘diffuse' SA pattern was found in 1 patient. Trichoscopy of the ‘moth-eaten' areas showed that alopecia is mainly due to a reduction in the number of terminal hairs. One patient with secondary syphilis showed trichodynia that regressed completely after antibiotic therapy. Limitations: The small number of patients included and the fact that none of our patients accepted to be biopsied in an affected area. Conclusion: Since SA appears to be present much more frequently than reported in the literature, when secondary syphilis is suspected, the patient should be examined for the presence of signs compatible with SA and the scalp should be examined by dermoscopy.

BACKGROUND: Melanocytic naevi located in special sites, such as the vulvar mucosa might present peculiar clinical and dermatoscopic features. OBJECTIVES: We describe a management proposal of a genital naevus associated with inflammatory disorders that aims to facilitate the clinical and pathologic diagnosis. METHODS: Videodermoscopy of a genital naevus associated with lichen sclerosus of an 8-year-old girl, was carried out before and 2 months after treatment with topical steroids. An excisional biopsy and immunohistochemical studies with HMB-45, MART -1 and molecular studies with p 16 staining were performed. RESULTS: The features of the melanocytic lesion associated with lichen sclerosus were troublesome on the basis of clinical and videodermoscopic evaluation. Histopathologic and immunohistochemical examination performed after topical treatment, showed a compound melanocytic naevus with an underlying inflammation consistent with lichen sclerosus. CONCLUSIONS: The evaluation of genital naevi should take into account the presence of inflammatory disorders, not uncommon in such location. Treatment of the latter and short follow-up of the patients, can avoid over-diagnosis of malignancies and extensive surgical procedures. Background Melanocytic naevi located in special sites, such as the vulvar mucosa might present peculiar clinical and dermatoscopic features. Objectives We describe a management proposal of a genital naevus associated with inflammatory disorders that aims to facilitate the clinical and pathologic diagnosis. Methods Videodermoscopy of a genital naevus associated with lichen sclerosus of an 8-year-old girl, was carried out before and 2 months after treatment with topical steroids. An excisional biopsy and immunohistochemical studies with HMB-45, MART -1 and molecular studies with p 16 staining were performed. Results The features of the melanocytic lesion associated with lichen sclerosus were troublesome on the basis of clinical and videodermoscopic evaluation. Histopathologic and immunohistochemical examination performed after topical treatment, showed a compound melanocytic naevus with an underlying inflammation consistent with lichen sclerosus. Conclusions The evaluation of genital naevi should take into account the presence of inflammatory disorders, not uncommon in such location. Treatment of the latter and short follow-up of the patients, can avoid over-diagnosis of malignancies and extensive surgical procedures.

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