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Blue nevus-like lesions constitute a category of melanocytic lesions clinically identified by their blue coloration. Histologically, they exhibit two primary features: a dermal location and intense pigmentation. The latest World Health Organization (WHO) classification categorizes blue melanocytic lesions into benign entities (dermal melanocytoses, blue nevus, and deep penetrating nevus), melanocytic tumors with low to intermediate malignant potential (pigmented epithelioid melanocytoma, PEM), and malignant lesions (blue nevus-like melanoma and melanoma arising in blue nevus). Clinically, blue nevi are enduring and stable lesions, displaying a structureless blue pigmentation both clinically and dermatoscopically, with a straightforward histologic diagnosis. Conversely, lesions with recent onset and/or rapid growth are more commonly associated with diagnoses falling within the intermediate part of the spectrum or with melanoma. These lesions often present with a blue color along with additional features such as black blotches, irregular vessels, and irregular pigmented globules. They typically emerge de novo without recognizable precursors, they pose significant challenges for patient management. Melanoma on a blue nevus is an exceedingly rare entity with only a few cases described to date. Histologically, differentiating between lesions with intermediate malignant potential and melanoma is always challenging, necessitating a comprehensive evaluation of all morphologic findings of the lesion.

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The global healthcare sector faced immense challenges due to the COVID-19 pandemic. Oncologists noted reduced cancer screening, which impacted melanoma diagnosis and treatment, leading to concerns about delayed care and poorer outcomes. This review analyzes how the pandemic influenced melanoma ulceration risk and Breslow thickness index through a meta-analysis of published studies. Following PRISMA guidelines, we conducted a systematic review of literature from January 2021 to December 2022 on cutaneous melanoma before and during the COVID-19 pandemic. Upon screening 1854 manuscripts, the review led to 13 studies meeting inclusion standards. The quality assessment followed MINORS and Newcastle-Ottawa Scale criteria. Regarding ulceration, post-COVID ulceration surpassed pre-COVID levels significantly, with a risk ratio of 1.31 and an estimated odds ratio of 1.41, indicating a 44% rise post-COVID. As for Breslow thickness, studies show a rising trend in the Breslow index post-COVID, but less significantly, with an effect size of 0.08 regarding the meta-analysis model (P = 0.02) with a pre-COVID mean Breslow of 1.56 mm and post-COVID of 1.84 mm. This meta-analysis concluded that post-COVID ulceration rates significantly surpassed pre-COVID levels. Considering that ulcerated melanomas usually undergo sentinel lymph node biopsy and are more likely to benefit from adjuvant therapies, this indicates important implications, as many patients might have missed the opportunity to start therapy appropriately, regardless of their Breslow thickness status.

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INTRODUCTION: Stage IIA cutaneous melanoma is typified by a Breslow thickness between 1.1 and 2.0 mm with ulceration or between 2.1 and 4.0 mm without ulceration. The role of radiological investigations in staging and follow-up of this intermediate-risk subgroup of patients is still debated. OBJECTIVES: The aim of this study is to investigate the role of imaging procedures in the follow-up of stage IIA melanoma asymptomatic patients. METHODS: Data were retrieved from two tertiary referral centers in Italy. Among patients with stage IIA melanoma, those who relapsed were investigated concerning type of detection (by patient or by doctor), and modality of detection (clinical examination, ultrasound, CT scan). In addition, false positive data were collected. RESULTS: In total, 213 patients were retrieved, with 26 patients showing relapse (recurrence rate, 12.2%). The mean follow-up time was 3 years and the mean time to recurrence was 17.8 months. 21/26 (80.7%) recurrences were identified by the doctor and 5/26 (19.2%) by the patient (P < 0.05). Among those identified by the doctor, 16/21 (76,1%) were identified by radiological examinations. Nine out of 15 (60%) lymph node recurrences were detected by ultrasound and 6/7 (85.7%) distant metastases were detected by CT. The false positive rate was 7% (P < 0.05). CONCLUSIONS: In our study the great majority of metastases were detected using imaging procedures. Given the new therapeutic options offered by targeted therapy and immunotherapy in relapsing patients, the role of radiological investigations in the follow-up of stage IIA patients should be reconsidered.

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Sentinel lymph node biopsy (SLNB) is a surgical procedure aimed to detect nodal metastases in patients with clinically occult disease. Since the advent of new systemic therapies, its role in melanoma has been extensively debated over the last years. In this article, three possible scenarios are discussed, considering the SLNB impact on the management of melanoma patients. First, pT1b and pT2a patients with negative SLNB (stages IA and IB) and those with positive SLNB (stage IIIA) would all not benefit from adjuvant treatment. Therefore, SLNB might be avoided in these categories of patients. Second, in IIB and IIC, melanoma patients are already candidates for adjuvant treatment; therefore, SLNB in patients with T3b, T4a, or T4b melanoma would not change treatment decisions. On the other end of the spectrum, patients with pT2b and pT3a melanomas (clinical stage IIA) represent the only two groups whose management would be significantly affected by the SLNB status, being adjuvant therapy only indicated for SLN-positive patients. Further studies are needed to investigate which melanoma patient deserves SLNB.

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(1) Background: Nevus-associated cutaneous melanoma (CM) is relatively common in the clinical practice of dermatopathologists. The correct diagnosis and staging of nevus-associated cutaneous melanoma (CM) mainly relies on the correct discrimination between benign and malignant cells. Recently, PRAME has emerged as a promising immunohistochemical marker of malignant melanocytes. (2) Methods: PRAME immunohistochemistry (IHC) was performed in 69 cases of nevus-associated CMs. Its expression was evaluated using a score ranging from 0 to 4+ based on the percentage of melanocytic cells with a nuclear expression. PRAME IHC sensitivity, specificity, positive predictive values, and negative predictive values were assessed. Furthermore, the agreement between morphological data and PRAME expression was evaluated for the diagnosis of melanoma components and nevus components. (3) Results: PRAME IHC showed a sensitivity of 59%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 71%. The diagnostic agreement between morphology and PRAME IHC was fair (Cohen's Kappa: 0.3); the diagnostic agreement regarding the benign nevus components associated with CM was perfect (Cohen's Kappa: 1.0). PRAME was significantly more expressed in thick invasive CMs than in thin cases (p = 0.02). (4) Conclusions: PRAME IHC should be considered for the diagnostic evaluation of nevus-associated CM and is most useful in cases of thick melanomas. Pathologists should carefully consider that a PRAME-positive cellular population within the context of a nevus could indicate a CM associated with the nevus. A negative result does not rule out this possibility.

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The field of skin cancer detection offers a compelling use case for the application of artificial intelligence (AI) within the realm of image-based diagnostic medicine. Through the analysis of large datasets, AI algorithms have the capacity to classify clinical or dermoscopic images with remarkable accuracy. Although these AI-based applications can operate both autonomously and under human supervision, the best results are achieved through a collaborative approach that leverages the expertise of both AI and human experts. However, it is important to note that most studies focus on assessing the diagnostic accuracy of AI in artificial settings rather than in real-world scenarios. Consequently, the practical utility of AI-assisted diagnosis in a clinical environment is still largely unknown. Furthermore, there exists a knowledge gap concerning the optimal use cases and deployment settings for these AI systems as well as the practical challenges that may arise from widespread implementation. This review explores the advantages and limitations of AI in a variety of real-world contexts, with a specific focus on its value to consumers, general practitioners, and dermatologists.

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BACKGROUND: Methyl aminolevulinate (MAL) photodynamic therapy (PDT) is commonly used for field treatment of actinic keratoses (AKs). In standard natural daylight PDT (n-DL-PDT) the first step, after the application of chemical solar filter, is removal of crusts and scales by curettage, followed by the application of MAL cream. Some patients experience intense pain during curettage and stinging after application of the photosensitizer to just curettaged skin. OBJECTIVES: To evaluate whether n-DL-PDT without curettage, but preceded by application of keratolytics, would maintain a similar efficacy, based on clinical, dermoscopic, reflectance confocal microscopy (RCM) assessments, safety and patient satisfaction as standard n-DL-PDT with curettage. METHODS: Forty patients with multiple AKs on the face and/or scalp were enrolled in this study. Patients were randomized into two groups of treatment as follows: (i) MAL n-DL-PDT without previous curettage, preceded by skin preparation at home with keratolytics (30% urea cream, twice a day for 7 days; -Cur group) and (ii) MAL n-DL-PDT preceded by skin preparation at the hospital with curettage (+Cur group). RESULTS: Thirty-nine participants completed the study. Four hundred and twenty-one AKs in -Cur group and 337 AKs in +Cur group were treated. The mean reduction in the number of AK lesions 3 months after the treatment was 10.7 (-54.7%) in the -Cur and 10.4 (-58.7%) in the +Cur group. We found that the differences in terms of efficacy and patient satisfaction comparing the two treatment regimens were not statistically significant. The pain score reported during and after daylight exposure was similar and low in both groups. Moreover, no unexpected adverse events occurred during the trial period. CONCLUSIONS: According to our results, curettage is not necessary to obtain the full treatment effect of n-DL-PDT. We experienced in a real-life setting that n-DL-PDT protocol could be changed by replacing curettage with keratolytics.

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INTRODUCTION: Although the dermoscopic features of facial lentiginous melanomas (LM), including lentigo maligna and lentigo maligna melanoma, have been extensively studied, the literature about those located on the scalp is scarce. This study aims to describe the dermoscopic features of scalp LM and assess the diagnostic accuracy of dermoscopy to discriminate them from equivocal benign pigmented macules. METHODS: Consecutive cases of scalp LM and histopathology-proven benign but clinically equivocal pigmented macules (actinic keratoses, solar lentigos, seborrhoeic keratoses, and lichen planus-like keratoses) from four referral centres were included. Dermoscopic features were analysed by two blinded experts. The diagnostic performance of a predictive model was assessed. RESULTS: 56 LM and 44 controls were included. Multiple features previously described for facial and extrafacial LM were frequently identified in both groups. Expert's sensitivity to diagnose scalp LM was 76.8% (63.6-87.0) and 78.6% (65.6-88.4), with specificity of 54.5% (38.9-69.6) and 56.8% (41.0-71.7), and fair agreement (kappa coefficient 0.248). The strongest independent predictors of malignancy were (OR, 95% CI) chaos of colour (15.43, 1.48-160.3), pigmented reticular lines (14.96, 1.68-132.9), increased density of vascular network (3.45, 1.09-10.92), and perifollicular grey circles (2.89, 0.96-8.67). The predictive model achieved 85.7% (73.8-93.6) sensitivity, 61.4% (45.5-75.6) specificity, and 81.5 (73.0-90.0) area under curve to discriminate benign and malignant lesions. A diagnostic flowchart was proposed, which should improve the diagnostic performance of dermoscopy. CONCLUSION: Both facial and extrafacial dermoscopic patterns can be identified in scalp LM, with considerable overlap with benign pigmented macules, leading to low specificity and interobserver agreement on dermoscopy.

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INTRODUCTION: Seborrheic keratoses (SK), are very common benign skin lesions, which may increase in number and size with age. OBJECTIVES: The aim of the study was to assess any differences seen in seborrheic keratoses in relation to different skin types (ST) and lesion location. METHODS: This was a retrospective observational study of 10-months period, based on dermoscopic images of seborrheic keratoses and patient history recorded in database. Patients were categorized according to their age, sex, skin type, and location of SK. RESULTS: The frequency of SK remained high on the back for skin type 1, 2, 3 and 4. This same trend was also seen on the face and chest. In skin type 3 we saw a reversal of distribution of SK, the highest frequency remained on the back, and this was followed by the chest rather than the face. In skin type 5 and 6, the nature of the distribution of SK was more facial, CONCLUSIONS: In summary our study shows that SK are more commonly seen in males than in females, they tend to dominate in sun exposed sites especially the back and the face. Both the smaller and larger sized SK dominated in ST 1 and 2. The lighter to darker shades of color seen in seborrheic keratoses varied in accordance with the skin type, with lighter colored SK being seen more in lighter skin types as compared to darker skin types, whereas bluish colored SK were seen in all skin types except ST 1.

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BACKGROUND: Cutaneous adverse events (CAEs) related to oncological therapies are a common scenario in daily clinical practice. METHODS: This is a retrospective observational study collecting the data regarding CAEs of patients treated with immune checkpoints inhibitors (ICIs) in four different Italian centers. RESULTS: Of 323 patients included, 305 were evaluable for this analysis; 182 patients (59.7%) had metastatic cutaneous melanoma (CM), 99 (32.5%) non-small cell lung cancer (NSCLC) and 24 (7.8%) renal cell carcinoma (RCC). The most frequent CAEs that we found, considering all the 305 patients, were pruriginous maculopapular rash (10.2% of the patients), vitiligo-like areas (7.2% of the patients), psoriasiform rash (6.2% of the patients), asymptomatic maculopapular rash (4.6% of the patients), and lichenoid rash (4.3% of the patients). Vitiligo-like areas occurred more frequently in patients with CM, while a lichenoid rash was more frequently observed in patients with RCC. Treatment interruption was related to drug-induced CAEs in 15.4% of melanoma patients and 0.0% of lung and kidney patients. Patients developing a cutaneous adverse event had better overall response rate and higher progression free survival and overall survival than the patients without CAEs. CONCLUSIONS: Our study brings new information on the characteristics of CAEs related to ICIs treatment in three different types of cancers, CM, NSCLC and RCC.

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INTRODUCTION: Phosphodiesterase 5 inhibitors (PDE5-is) are used worldwide as first line therapy for erectile dysfunction (ED). Current literature reported data on the warning association between PDE5-is use and the development of cutaneous melanoma. However, these data are contrasting, thus we aim to summarise evidence regarding this association. CONTENT: A systematic review of all published articles related to the effects of PDE5-is in the development of cutaneous melanoma was performed. PubMed, EMBASE, and Cochrane library were queried for all the published studies indexed up to the 26th of May 2023. A combination of keywords related to PDE5-is and melanoma were used. Only original studies based on human subjects in the English language were included in the analysis. SUMMARY AND OUTLOOK: Of 505 articles identified, only eight original articles were considered for further analysis. Overall, five of the selected articles including 657,984 subjects agrees on an increased risk of developing melanoma in PDE5-is users. On the other hand, three original articles based on data regarding 360,915 subjects, disagree with the previous statement declaring any association between PDE5-i use and melanoma. Current literature still reports contrasting data regarding the association between PDE5-is assumption and increased risk of melanoma, but a possible association is described, bringing attention to higher risk melanoma category of patients. More clinical studies are needed to clarify the impact of PDE5-is in the development and progression of melanoma.

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BACKGROUND: Extra facial lentigo maligna (EF-LM) arises outside the head and neck area. EF-LM presents the classic histological features of lentigo maligna. The dermoscopic aspects of EF-LM have been poorly studied. OBJECTIVE: The primary aims of our study were to analyse and describe the clinical, dermoscopic and confocal microscopy features of a series of histologically confirmed EF-LM. METHOD: We conducted a retrospective and multicentric study. From our database, we selected 48 cases of thin melanomas on photodamaged skin with histological features of EF-LM of which clinical, dermoscopic and confocal microscopy images were available, and a control group of 45 lesions, that can be subjected to differential diagnosis such as solar lentigo, lichenoid keratosis, seborrheic keratosis and melanocytic nevi, of which dermoscopic and confocal microscope images were available. RESULTS: Extra facial lentigo maligna had a higher prevalence of lentigo-like pigment patterns, angulated lines and zigzag structures. At confocal microscopy, LM-EF cases showed a higher prevalence of pagetoid spreading, round cells, dendritic cells in the epidermis, atypical cells at the dermo-epidermal junction, dendritic cells at the junction, meshwork pattern and elastosis. Our study shows that reflectance confocal microscopy (RCM) has a sensitivity of 90% and a specificity of 97% for the differential diagnosis of this type of melanoma. CONCLUSIONS: Extra facial lentigo maligna does not have the classic dermoscopic features of superficial spreading melanoma, the most observed dermoscopic criteria are angulated lines and lentigo-like pigment patterns without lentigo-like border. RCM can be a valuable imaging tool for the evaluation of all those suspicion skin lesions at dermoscopy highlighting cellular atypia suggestive for melanoma.

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BACKGROUND: The management of cytological samples can significantly impact diagnostic interpretation. Cell blocks (CB) are a popular method due to their ability to provide additional morphological information and be used for immunocytochemistry and molecular tests. Recently, a new CB technique called the synthetic matrix CytoMatrix (CM) has been introduced, which can gather and hold cytological material within its three-dimensional structure. METHODS: In this study, 40 cytological samples from patients with melanoma metastases were analyzed to evaluate the diagnostic performance of CM compared to another CB method used in the laboratory. The researchers assessed the morphological adequacy of the two techniques, as well as their performance in immunocytochemical analysis and molecular. RESULTS: This study showed that CM was quicker and equally effective compared to the other method, with the laboratory technician having less of an impact on the CM approach across all passages. Additionally, all CMs were adequate, whereas the other method was adequate in 90% of cases. Immunocytochemistry confirmed the diagnosis of melanoma metastases in all cases, and all 40 CMs and 36 of the other method were adequate for fluorescence in situ hybridization analysis. CONCLUSION: CM is a low-time-consuming technology that is unaffected by technicians during all setup phases, making it simpler to standardize the procedure. Moreover, a low loss of diagnostic cells ensures greater benefits for morphological analysis, immunocytochemistry, and molecular testing. Overall, the study highlights the potential of CM as a valuable technique for managing cytological samples.

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BACKGROUND: Incidence of cutaneous melanoma is steadily growing, and its early recognition is of paramount importance. Small, pigmented lesions often represent a challenge for the clinician, as predictors of melanoma have not yet been uniquely identified in this setting. OBJECTIVES: To identify dermoscopic features that aid in distinguishing small diameter melanomas (≤5 mm) from equivocal melanocytic nevi measuring ≤5 mm. METHODS: A retrospective multicenter study was conducted to collect demographics, clinical and dermoscopic pictures of (i) histology-proven flat melanomas, measuring ≤5 mm, (ii) histology-proven but clinically/dermoscopically equivocal melanocytic nevi measuring ≤5 mm, and (iii) histology-proven flat melanomas, measuring >5 mm. An independent dermoscopic evaluation was performed. Differences in predefined dermoscopic features were assessed across the three groups. RESULTS: A total of 103 melanomas measuring ≤5 mm were collected; 166 control lesions, comprising 85 large (>5 mm) melanomas and 81 dubious, clinically equivocal melanocytic nevi measuring ≤5 mm were included. Of the 103 mini-melanomas, only 44 were melanoma in situ. Five dermoscopic predictors of melanoma were identified for the assessment of flat, non-facial melanocytic lesions measuring ≤5 mm, namely: atypical pigment network, blue-white veil, pseudopods, peripheral radial streaks, and presence of more than one color. The latter were combined into a predictive model capable of identifying melanoma with 65% sensitivity and 86.4% specificity, at a cut-off score of 3. Among melanomas measuring ≤5 mm, presence of a blue-white veil (P = 0.0027) or negative pigment network (P = 0.0063) was associated with invasiveness. CONCLUSION: A set of five dermoscopic predictors of melanoma, atypical pigment network, blue-white veil, pseudopods, peripheral radial streaks, and presence of more than one color is proposed for the assessment of flat, non-facial melanocytic lesions measuring ≤5 mm.

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INTRODUCTION: Spitz nevi (SN) are benign melanocytic proliferations frequently occurring in children. Some pigmented SN with a starburst pattern evolve into the "stardust" one, which is characterized by a central, black to gray, hyperpigmented area and remnants of a brown network at the periphery. These dermoscopy changes are often the first alert to induce excision. OBJECTIVES: The aim of this study is to enlarge the case series of stardust SN in children, in order to increase confidence with this new dermoscopic pattern and reduce unnecessary excisions. METHODS: This retrospective observational study was conducted with SN cases received from IDS members. The inclusion criteria were: clinical and/or histopathologic diagnosis of Spitz naevus with starburst appearance in children <12 years old, availability of a dermoscopic image at baseline and after follow-up of at least 1 year, availability of patient data. The dermoscopic images and their changes over time were assessed by three evaluators in consensus. RESULTS: 38 SN were enrolled, with a median age of 7 years and a median FUP duration of 15,5 months. Comparing the evolution with time of FUP, no significant differences were found between growing and involuting lesions in terms of patient age and sex, location and palpability of lesions. CONCLUSIONS: The long follow-up reported in our study could really support the concept of benignity of changing SN. A conservative approach is acceptable for nevi showing the stardust pattern, because it may be considered a physiological evolution of pigmented Spitz nevus, and urgent surgeries could be avoided.

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INTRODUCTION: Melanoma on the head/neck area can show subtle clinical, dermoscopic and histologic features at early stages, being difficult to differentiate from junctional nevi. OBJECTIVES: This case series aims to raise awareness on the topic of misdiagnosis of early lentigo maligna as junctional nevi. METHODS: From the databases of three pigmented lesion clinics in Italy, Australia, and France, we retrieved all cases of lesions of the head/neck area with an initial histopathologic diagnosis of junctional nevus (JN) or dysplastic junctional nevus (DJN) which subsequently recurred and were ultimately diagnosed as melanoma. Moreover, we also retrieved those cases with an initial diagnosis of JN/DJN made on a partial biopsy that were diagnosed as melanoma after complete surgical removal. RESULTS: Here we report 14 cases in which the initial histologic diagnosis was junctional nevus or dysplastic junctional nevus. The lesions recurred over time with a final diagnosis of lentigo maligna. CONCLUSIONS: Clinicians should critically question a given histologic diagnosis of junctional or dysplastic junctional nevus on the head/neck area if the clinical or dermoscopic features are discordant. Clinico-pathologic correlation is the best way to increase diagnostic accuracy and optimize management for the patient.