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Background: Melanoma metastasis to distant sites is associated with diminished survival rates and poor prognosis. Except of Breslow thickness and ulceration that are currently used in melanoma staging, the investigation of additional clinicopathological, dermatoscopic and molecular factors that could predict tumors with aggressive biologic behavior is of paramount importance., Methods: A literature search was conducted in PubMed, Scopus, Cochrane databases and gray literature until November 2023. Observational studies (including cohorts and case-control studies) were included and clinical and histopathological factors of primary cutaneous melanomas, along with dermatoscopic and molecular predictors of distant metastasis (DM) and distant metastasis-free survival (DMFS) were assessed. Random - effect models were preferred, the results were presented as Hazard Ratios (HRs) with 95 %Confidence Intervals (CIs) and the I 2 index quantified heterogeneity. Subgroup analysis according to AJCC stage and sensitivity analysis were also conducted., Results: One hundred forty-three and 101 studies were included in the qualitive and quantitative synthesis, respectively. Regarding clinical factors, males, compared to females, and head and neck location, compared to trunk, demonstrated higher risk for DM [n=36, HR 1.49, 95%CI 1.36 - 1.63, I 2 33% and n=21, HR 1.24, 95 %CI 1.01 - 1.52, I 2 62 %]. Both factors had similar effects on DMFS. Breslow thickness and ulceration were significant predictors or DM. Additional factors that posed an increased risk for DM were nodular (n=15, HR 2.51, 95 %CI 1.83 - 3.43, I 2 56 %) and lentigo maligna subtypes (n=12, HR 1.87, 95 %CI 1.27 - 2.75, I 2 0 %), compared to superficial spreading subtype, lymphovascular invasion (n=9, HR 2.05, 95 %CI 1.18 - 3.58, I 2 78 %), SLN positivity and BRAF+ mutational status. In contrast, regression was a negative predictor of DM (n=15, HR 0.59, 95 %CI 0.44 - 0.79, I 2 68 %). Two studies focused on dermatoscopic factors and found that low pigmentation and the presence of blue-white veil might predict DM development. The results of subgroup analysis for stage I-II patients were essentially similar and sensitivity analysis did not reveal significant alterations, despite the moderate or high heterogeneity in some categories., Conclusions: Clinical and histological characteristics of the tumor along with dermatoscopic features and molecular parameters hold significant prognostic information and could be incorporated into models to predict melanomas with high metastatic potential., Competing Interests: Declaration of Competing interest The authors declare that they have no known competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Melanoma disease patterns vary with patient age., Aim: To evaluate sentinel lymph node biopsy (SLNB) in managing melanoma at differing patient ages., Methods: Online prediction tools were applied to compare SLNB positivity (SLNB + ) and survival risk at patient ages 20-80. Tübingen melanoma data were used to determine variations in the hazard ratio of SLNB + for mortality at different patient ages., Results: Regardless of tumour thickness, predicted SLNB + rates were markedly higher than mortality rates for 20-year-old patients. For 80-year-old patients, it is the opposite., Discussion: If 1000 20-year-olds with a 0.4 mm thickness non-ulcerated melanoma underwent SLNB, 100 would likely be positive. If all 100 were to be offered adjuvant drug therapy (ADT), fewer than three more melanoma deaths in those 1000 patients would be avoided. In total, 97 patients would have received medication they may never have needed. If 1000 80-year-olds with a 3 mm thickness non-ulcerated melanoma underwent SLNB, only 40 would likely be positive. In total, 274 patients would be predicted to die of melanoma, 245 being SLNB negative and 29 SLNB + . ADT linked to SLNB + could deny treatment to 89% of these high-risk patients., Limitations: The authors relied on published risk data., Conclusion: SLNB has poor specificity at predicting mortality in young melanoma patients and poor sensitivity in older patients. SLNB is not indicated in managing cutaneous melanoma for patients under 40 or over 60 years of age. Many such patients could be managed with wide local excision alone in their clinician's office-based practice. For all cutaneous melanoma patients at all ages, linking ADT to BAUSSS biomarker, (an algorithm of Breslow thickness, age, ulceration, subtype, sex and Site) rather than SLNB + is likely more appropriate. BAUSSS provides a more accurate melanoma-specific mortality risk assessment for patients without burdening them with added surgery, hospitalization, costs or morbidity risk., (© 2024 European Academy of Dermatology and Venereology.)

Background: Breslow thickness, patient age and ulceration are the three most valuable clinical and pathological predictors of melanoma survival. A readily available reliable online tool that accurately considers these and other predictors could be valuable for clinicians managing melanoma patients., Objective: To compare online melanoma survival prediction tools that request user input on clinical and pathological features., Methods: Search engines were used to identify available predictive nomograms. For each, clinical and pathological predictors were compared., Results: Three tools were identified. The American Joint Committee on Cancer tool inappropriately rated thin tumours as higher risk than intermediate tumours. The University of Louisville tool was found to have six shortcomings: a requirement for sentinel node biopsy, unavailable input of thin melanoma or patients over 70 years of age and less reliable hazard ratio calculations for age, ulceration and tumour thickness. The LifeMath.net tool was found to appropriately consider tumour thickness, ulceration, age, sex, site and tumour subtype in predicting survival., Limitations: The authors did not have access to the base data used to compile various prediction tools., Conclusion: The LifeMath.net prediction tool is the most reliable for clinicians in counselling patients with newly diagnosed primary cutaneous melanoma regarding their survival prospects., (© 2023 European Academy of Dermatology and Venereology.)

The current evidence on paediatric melanoma is heterogeneous, especially regarding the prognosis of different histological subtypes. We sought to systematically review the evidence on paediatric melanoma, highlighting the major sources of heterogeneity and focusing on available data on single patients. A systematic search was performed from 1948 to 25 January 2021. Only studies reporting at least one case of cutaneous melanoma in patients aged ≤18 years were included. Unknown primary and uncertain malignant melanomas were excluded. Three couples of authors independently performed title/abstract screening and two different authors reviewed all the relevant full texts. The selected articles were manually cross-checked for overlapping data for qualitative synthesis. Subsequently data on single patients were extracted to perform a patient-level meta-analysis. PROSPERO registration number: CRD42021233248. The main outcomes were melanoma-specific survival (MSS) and progression-free survival (PFS) outcomes. Separate analyses were done of cases with complete information on histologic subtype, focusing on superficial spreading (SSM), nodular (NM) and spitzoid melanomas, as well as of those classified as de-novo (DNM) and acquired or congenital nevus-associated melanomas (NAM). The qualitative synthesis covered 266 studies; however, data on single patients were available from 213 studies including 1002 patients. Among histologic subtypes, NM had a lower MSS than both SSM and spitzoid melanoma, and a lower PFS than SSM. Spitzoid melanoma had a significantly higher progression risk than SSM and trended toward lower mortality. Focusing on nevus-associated status, DNM demonstrated better MSS after progression than congenital NAM, and no differences were highlighted in PFS. Our findings describe the existence of different biological patterns in paediatric melanoma. Specifically, spitzoid melanomas demonstrated intermediate behaviour between SSM and NM and showed a high risk of nodal progression but low mortality. This raises the question of whether spitzoid lesions are being over-diagnosed as melanoma in childhood., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Whether menopausal hormone therapy (MHT) increases the risk of skin cancer is controversial., Aim: To systematically review and meta-analyze evidence regarding the association of MHT with the risk of melanoma and keratinocyte cancer (KC)., Material and Methods: A comprehensive literature search was conducted of the PubMed, Scopus and Cochrane databases, through to 30 October 2021. Skin neoplasms were divided into melanoma and KC. In the latter category, both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were considered. The results are presented as hazard ratios (HR) with 95 % confidence intervals (CI). The I 2 index was used to assess heterogeneity. Subgroup analysis and sensitivity analysis were also conducted in order to explore potential differences among studies., Results: Twenty-seven studies were included in the qualitative and 23 in the quantitative analysis, with a total of 2,612,712 menopausal women (25,126 with skin cancer; 20,150 with melanoma). MHT was associated with an increased risk of melanoma (HR 1.11; 95 % CI 1.05-1.19; I 2 45%). With regard to MHT type, both estrogen monotherapy (HR 1.22, 95 % CI 1.16-1.29; I 2 0%) and estrogen in combination with progestogen (HR 1.11, 95 % CI 1.05-1.18, I 2 26%) significantly increased that risk. Regarding melanoma subtype, superficial spreading melanoma (SSM) and lentigo maligna melanoma (LMM) were the only histologic subtypes associated with MHT use. MHT was also associated with an increased risk of KC (HR 1.17, 95 % CI 1.04-1.31, I 2 83%), specifically BCC (HR 1.22, 95 % CI 1.12-1.32; I 2 29%). Longer duration (>5 years) of MHT, current use and estrogen monotherapy were associated with an increased KC risk compared with no use., Conclusion: The use of MHT by postmenopausal women was associated with an increased risk of melanoma and KC. This risk was higher for current MHT users and those treated for over 5 years., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Peripheral globules (PG) in melanocytic lesions represent a concerning dermoscopic feature since they might be present in growing nevi and melanomas. Their natural evolution has not been fully elucidated, and an age-based management approach has been recommended., Objectives: The aim of this study was to calculate the growth rate of lesions with PG and investigate possible association with age, sex, location, and the global dermoscopic pattern., Methods: We retrospectively selected the lesions of interest from a cohort of Caucasian patients who underwent sequential digital dermoscopy monitoring. Lesions with PG distributed at 75% or more of their circumference with available follow-up images or histopathologic report were included. The surface area was automatically calculated with the help of an incorporated tool used in the acquisition of the images. The images were also evaluated by independent investigators for the presence of pre-defined criteria. Growth-curve models were used to assess the growth rate. The outcome variable was the area of nevi in mm2, and scatterplots with Lowess curves were used to present the mean change of nevi during follow-up., Results: A total of 208 lesions from 98 patients with a median age of 36 years (range 15-75) were included. The median follow-up time was 18 months (range 4-48). The mean growth rate for all nevi was 0.16 mm2/month (95% CI, 0.14-0.18, p < 0.001), ranging from -0.29 to 0.61 mm2/month. The growth rate was higher in nevi with a homogeneous dermoscopic pattern (p < 0.001). The number of peripheral globules during follow-up varied from increasing to complete disappearance. None of the lesions developed any melanoma-specific structure at follow-up., Conclusion: Nevi with PG grew at a mean rate of 0.16 mm2/month, and the growth rate was independent of age, gender, or anatomic location. Nevi with homogeneous pattern demonstrated the highest growth rate in our cohort. None of the monitored nevi with PG developed melanoma-specific criteria at follow-up., (© 2023 S. Karger AG, Basel.)

Background: The prevalence of acral nevi and their dermatoscopic patterns have been mainly studied in Asian populations. Few data exist on the prevalence and clinico-dermatoscopic morphology of acral nevi in white populations., Objectives: The aim of this study was to assess the prevalence of acral nevi and evaluate their features in a cohort of Caucasian individuals at high risk for skin cancer., Methods: We prospectively examined the palms and soles of 680 high-risk patients who underwent total body clinical and dermatoscopic documentation, as a part of their routine follow-up, between January 2016 and March 2020 at a skin cancer referral center in Greece., Results: Overall, 334 acral lesions were detected in 217 (37.0%) of 585 patients in the study. The presence of acral nevi was associated with 2.6 higher odds of a total nevus count higher than 50 (OR: 2.6, p < 0.05, confidence intervals [CI]: 1.11-6.09). Of 334 acral nevi, 65.0% were clinically flat and 35.0% were clinically palpable. Palpable lesion had 19-fold higher probability of being located on the sole (OR: 19.44, p < 0.05, CI: 3.91-96.7). The parallel furrow pattern was present in 147 lesions (44.0%). In 76 lesions (22.8%), we observed a previously undefined pattern consisting of wavy lines, which was correlated with clinically palpable lesions (p < 0.001). The third most common pattern was homogeneous (10.5%), followed by the fibrillar (8.7%), the lattice-like (7.2%), the reticular (3.6%), and globular (3.3%)., Conclusion: We observed a higher prevalence of benign acral melanocytic lesions than expected, probably related to our cohort selection of patients at high risk for developing skin cancer. Our study confirms the previously described dermatoscopic patterns and provides novel insights into the dermatoscopic morphology of acral palpable nevi, for which we described a new benign pattern consisting of wavy lines., (© 2023 S. Karger AG, Basel.)

Competing Interests: Conflicts of interest None disclosed.

Background: The dermoscopic features of classic patch stage mycosis fungoides (MF) have been described, but data on plaque and tumoral stage as well as rarer MF subtypes is limited., Objective: To evaluate dermoscopic morphology and dermoscopic-pathological correlations of classic MF stages and investigate dermoscopic features of MF variants., Methods: Patients with histopathologically confirmed lesions of classic MF (patch, plaque and tumoral stage) or folliculotropic, erythrodermic and poikilodermatous MF were included. Standardized evaluation of dermoscopic pictures of the included MF variants and comparative analysis and dermoscopic-pathological correlation assessment of different stages of classic MF were performed., Results: A total of 118 instances were included (75 classic MF, 26 folliculotropic MF, 9 erythrodermic MF and 8 poikilodermatous MF). Linear/linear-curved vessels and white scales in the skin furrows were significantly associated with patch-stage MF, while clustered dotted vessels were related to plaque-stage MF and peripheral linear vessels with branches, ulceration and red globules separated by white lines to tumour-stage MF. Moreover, patchy white scales were significantly more common in patches and plaques compared to tumours, whereas focal bright white structureless areas were related to plaque and tumoral stage. Vessels histopathologically corresponded to dilated vascular structures in the dermis, orange structureless areas to either dermal hemosiderin (patch/plaque stage) or dense cellular infiltration (tumours), bright white lines/structureless areas to dermal fibrosis and ulceration to loss of epidermis. The main dermoscopic findings of folliculotropic MF were lack of hairs, dilated follicles and follicular plugs, while erythrodermic MF was mainly characterized by linear/dotted vessels, patchy white scales and focal orange structureless areas and poikilodermatous MF by focal white and brown structureless areas, white patchy scales and brown reticular lines., Conclusion: Dermoscopy may allow a more precise characterization of classic MF and reveal clues suggestive of the main MF variants., (© 2022 European Academy of Dermatology and Venereology.)

Background: Limited data on dermatoscopy of nodular/plaque-type T-/B-cell primary cutaneous lymphomas (PCLs) is available., Objective: To describe dermatoscopic features of nodular/plaque-type PCLs, comparing them with those of clinical mimickers (pseudolymphomas, tumors, and inflammatory lesions) and investigating possible differences according to histologic subtypes., Methods: Participants were invited to join this retrospective, multicenter case-control study by submitting histologically/immunohistochemically confirmed instances of nodular/plaque-type PCLs and controls. Standardized assessments of the dermatoscopic images and comparative analyses were performed., Results: A total of 261 lesions were included (121 PCLs and 140 controls). Orange structureless areas were the strongest PCL dermatoscopic predictor on multivariate analysis compared with tumors and noninfiltrative inflammatory dermatoses. On the other hand, a positive association was found between PCLs and either unfocused linear vessels with branches or focal white structureless areas compared with infiltrative inflammatory dermatoses, whereas white lines were predictive of PCLs over pseudolymphomas. Differences in the vascular pattern were also seen between B- and T-cell PCLs and among B-cell PCL subtypes., Limitations: Retrospective design and the lack of a dermatoscopic-pathologic correlation analysis., Conclusion: Nodular/plaque-type PCLs display dermatoscopic clues, which may partially vary according to histologic subtype and whose diagnostic relevance depends on the considered clinical differential diagnoses., Competing Interests: Conflict of interest None disclosed., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Background: Metastasis from cutaneous squamous cell carcinoma (cSCC) mainly involve the regional nodal basin, with an incidence ranging from 2-4% until 15% in case of high-risk tumors. When dealing with high-risk cSCC, ultrasound examination is recommended every 3-4 months during follow-up. We aimed to determine the role of US examination in the early diagnosis of nodal metastasis from cSCC., Methods: We conducted a retrospective cohort study enrolling consecutive cases of histopathologically verified cSCCs from January 2007 to March 2018. All the enrolled cases were followed for at least one year and all cases of histopathologically verified metastasis were registered. We also reported if ultrasound of the regional basin was performed between the primary diagnosis and metastasis and how the latter was identified, through ultrasounds or clinically. A Kaplan-Meier survival analysis was conducted on patients undergoing ultrasounds during follow-up., Results: A total of 1881 cases, belonging to 1441 patients were included. Thirty-one cases of nodal metastasis diagnosed after the primary tumor, in as many patients, were identified. All of the selected metastasis derived from high-risk primary cSCCs. Only in 19 cases ultrasound examination was performed during follow-up; of these, 10 were diagnosed through ultrasounds and 9 clinically. Survival analysis demonstrated that the time interval between primary tumor and metastasis was significantly lower for patients with metastasis diagnosed by ultrasounds than clinically (P=0.036)., Conclusions: Our study highlighted the need to optimize the use of nodal ultrasound examination for high-risk cSCCs in order to early detect metastasis.

Background: Thin nodular melanoma (NM) often lacks conspicuous melanoma-specific dermatoscopic criteria and escapes clinical detection until it progresses to a thicker and more advanced tumour., Objective: To investigate the dermatoscopic morphology of thin (≤2 mm Breslow thickness) vs. thick (>2 mm) NM and to identify dermatoscopic predictors of its differential diagnosis from other nodular tumours., Methods: Retrospective, morphological case-control study, conducted on behalf of the International Dermoscopy Society. Dermatoscopic images of NM and other nodular tumours from 19 skin cancer centres worldwide were collected and analysed., Results: Overall, 254 tumours were collected (69 NM of Breslow thickness ≤2 mm, 96 NM >2 mm and 89 non-melanoma nodular lesions). Light brown coloration (50.7%) and irregular brown dots/globules (42.0%) were most frequently observed in ≤2 mm NMs. Multivariate analysis revealed that dotted vessels (3.4-fold), white shiny streaks (2.9-fold) and irregular blue structureless area (2.4-fold) were predictors for thinner NM compared to non-melanoma nodular tumours. Overall, irregular blue structureless area (3.4-fold), dotted vessels (4.6-fold) and serpentine vessels (1.9-fold) were predictors of all NM compared to non-melanoma nodular lesions., Limitations: Absence of a centralized, consensus pathology review and cases selected form tertiary centres maybe not reflecting the broader community., Conclusions: Our study sheds light into the dermatoscopic morphology of thin NM in comparison to thicker NM and could provide useful clues for its differential diagnosis from other non-melanoma nodular tumours., (© 2020 European Academy of Dermatology and Venereology.)

Background: Nevus-associated melanoma (NAM) has been regarded as a distinct biological entity from de-novo melanoma (DNM); however, static dermoscopy often fails in differentiating these entities. Digital dermoscopic monitoring allows to identify dynamic changes occurring during follow-up; this may improve diagnostic accuracy and potentially our knowledge on NAM biology. We aimed to define main independent factors associated with NAM diagnosis and those influencing follow-up time in a population of melanomas excised at follow-up., Methods: A cohort of melanomas excised at follow-up was retrospectively and consecutively selected. NAMs and DNMs were compared according to baseline features and main dermoscopic changes occurring during follow-up. Univariate and multivariable logistic and Cox's regression analysis were performed to respectively define factors associated with NAM diagnosis and those influencing the risk for excision., Results: Eighty-six melanomas were enrolled, of which 21 (24.4%) were nevus-associated. During follow-up NAMs mainly underwent atypical network modifications (47.6%), followed by inverse network (28.6%) and dermoscopic island (23.8%) worsening or appearance. DNMs were also mainly characterized by atypical network modifications (47.7%), however, a significant proportion of cases underwent irregular pigmentation/dots/globules or regression changes (29.2%), which were rarely seen among NAMs. Furthermore, both multivariable logistic and Cox's regression analysis demonstrated a significant association between NAM and a longer follow-up., Conclusions: We demonstrated that among melanomas excised at follow-up, different patterns of dermoscopic changes may be found between NAMs and DNMs. This finding, together with the association of NAM with a longer follow-up time, supports the hypothesis of different biological behavior of these two entities., (© 2020 the International Society of Dermatology.)

New drugs have been recently approved as adjuvant therapies for melanoma. In this Bayesian network meta-analysis, we aimed to assess the best therapeutic option in terms of recurrence-free survival (RFS), overall survival (OS) and adverse events (AEs). PubMed, Embase, Cochrane library and the American Society of Clinical Oncology databases were searched from inception until 20 August 2018. We estimated adjusted hazard ratios (HRs) for RFS and OS and relative odds ratios (ORs) for AEs and surface under the cumulative ranking (SUCRA) probabilities were calculated. A number of 872 records were identified, and six were finally included in the meta-analysis. A total of 4244 patients in six studies were randomized. The following therapies were considered in the selected studies: combined dabrafenib and trametinib, vemurafenib, nivolumab, ipilimumab and pembrolizumab. Nivolumab demonstrated the highest probability (75.1%) of being the best in term of RFS, followed by dabrafenib+trametinib, pembrolizumab, ipilimumab and vemurafenib; however, OS was not estimable. Concerning AEs, pembrolizumab and nivolumab showed the highest probability to be less associated with any and 3-4 grade AEs (83.1% and 64.4%, respectively). In conclusion, all new drugs are highly effective in adjuvant setting, and the best choice is dependent of patient's context., (© 2019 European Academy of Dermatology and Venereology.)

Background: In retrospective studies, a second primary melanoma (SPM) develops in 2%-20% of melanoma patients. Scarce evidence exists on the usefulness of total-body photography (TBP) and digital dermatoscopic documentation (DDD) for detecting SPMs., Objective: The primary aim was to quantify the risk and investigate the time of occurrence of SPMs. Secondary aims were to identify risk factors for SPM and to assess the usefulness of TBP and DDD for SPM detection., Methods: This prospective cohort included patients with recently diagnosed melanoma that underwent sequential clinical and dermatoscopic examinations for up to 5 years. Life table analysis and Kaplan-Meier survival analysis were performed. Multivariate Cox models were constructed to identify factors affecting the outcome., Results: An SPM developed in 46 of 977 (4.7%) patients. Life table analysis revealed a 5-year cumulative risk of 8.0% for SPM. High nevus count, fair phototype, and occupational sun exposure were potent predictors of SPM. Of all new melanomas, 17.3% were diagnosed by clinical and dermatoscopic examination, 48.1% by TBP, and 34.6% by DDD., Limitations: All patients followed the same protocol and diagnostic bias associated with sequential dermatoscopic imaging., Conclusion: In this cohort, melanoma patients were at 8% risk of an SPM developing within 5 years. TBP and DDD significantly contributed to the early detection of SPM., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Non-melanoma skin cancer (NMSC) is the commonest malignancy worldwide (>80% located in the head and neck area). The aim of this study was to assess risk factors predisposing to local recurrence of NMSC of the middle third of the face (MTF). This was a single-centre retrospective analysis of patients with NMSC of the MTF treated during 1995-2010. Data on epidemiological and tumour characteristics were collected. Survival analysis was performed and log-rank tests were used to compare differences in survival for each variable. A total of 531 patients with basal cell carcinoma (BCC) of the MTF were identified. Most tumours were nodular type (28.4%), located on the nose (34.3%), and confined to the dermis (75.5%). Negative margins were achieved in 91% of cases. Median follow-up time was 35 months and 15.2% of patients developed local recurrence. Incomplete excision was the only variable predisposing to local recurrence. The cohort also included 114 patients with squamous cell carcinoma (SCC). Most tumours were well differentiated (43.9%), located at the zygomatic area (49.1%), excised with negative margins (93%), and confined to the dermis (67.8%). At a median follow-up time of 42 months, local recurrence occurred in 15.7% of patients. Tumour size, depth of invasion, and prior history of head and neck SCC were risk factors for local recurrence. The variables predictive of recurrence of BCC were incomplete excision and for SCC tumour size, depth of invasion, and a prior history of head and neck SCC.

Since their first description by Sophie Spitz, Spitz nevi have been a subject of controversy among clinicians for many decades, and remain a clinical conundrum until today as their etiology, morphology, biological behavior and natural evolution is still not totally clear. This is because their clinical, dermoscopic and histopathologic features sometimes overlap with those of melanoma, rendering the management of spitzoid lesions particularly difficult. In addition, cases of histopatologically equivocal lesions do exist and their classification might sometimes be very challenging. Among several terms that have been used to describe these morphologically "intermediate" lesions, atypical Spitz tumor (AST) is the most widely used. The aim of this review paper was to describe the dermoscopic patterns and structures seen in Spitz/Reed nevi, spitzoid melanoma and AST. Finally, this article provides an evidence-based update on the available options for the management of spitzoid lesions, before and after histopathologic diagnosis.

Background: In vivo reflectance confocal microscopy significantly improves melanoma diagnosis as compared to clinical/dermoscopic examination alone. Several confocal criteria have been described allowing to differentiate melanoma from nevi; by combining different criteria, three pure confocal scores (Pellacani 2005, Segura 2009 and Pellacani 2012) and one mixed dermoscopic/confocal score (Borsari 2018) were constructed., Objective: Our aim was to externally validate and compare the performance of these confocal scores., Methods: We retrospectively enrolled excised melanocytic lesions which underwent confocal examination in a 2-year period. Lesions located on the face and acral sites were excluded. Both dermoscopic and confocal criteria considered in the four scores were evaluated by experts. Subsequently, specificity and sensitivity levels for each score were calculated, together with the positive and negative predictive values and likelihood ratios; also, receiver operating characteristic curves were constructed., Results: A total of 389 patients with 422 lesions were retrospectively enrolled, of which 162 (38.4%) were melanomas and 260 (61.6%) were nevi (189 common and 71 Spitz/Reed nevi). The highest sensitivity levels were recorded for Segura 2009 with cut-off ≥-1 (92.0%), while Pellacani 2005 with cut-off ≥5 achieved the highest specificity (69.6%). The score by Borsari et al. showed the highest levels of positive and negative predictive values (59.8% and 91.5%) and likelihood ratios (2.4 and 0.1) as well as the highest area under the curve values (0.76; 95% CI 0.72-0.81; P < 0.001)., Conclusions: High levels of accuracy were found for each of the four considered scores. No differences were found among scores in confirming melanoma diagnosis when positive; however, the score by Borsari 2018 was the best in excluding melanoma diagnosis when negative., (© 2019 European Academy of Dermatology and Venereology.)

Background: Frozen histological sections are used for intraoperative margin assessment during Mohs surgery. Fluorescence confocal microscopy (FCM) is a new tool that offers a promising and faster alternative to frozen histology., Objectives: To evaluate prospectively in a clinical setting the accuracy of FCM vs. frozen sections in margin assessment of basal cell carcinoma (BCC)., Methods: Patients with BCC scheduled for Mohs surgery were prospectively enrolled. Freshly excised surgical specimens were examined by FCM and then frozen sections were evaluated. Permanent sections were obtained, in order to validate the sample technique. A blind re-evaluation was also performed for discordant cases. Sensitivity and specificity levels, as well as positive and negative predictive values (PPV and NPV, respectively), were calculated and receiver-operating characteristic curves generated., Results: We enrolled 127 BCCs in as many patients (40·2% females). Seven hundred and fifty-three sections were examined. All BCCs were located in the head and neck area. In evaluating the performance of FCM vs. frozen sections, sensitivity was 79·8%, specificity was 95·8%, PPV was 80·5% and NPV was 95·7% [area under the curve 0·88, 95% confidence interval 0·84-0·92 (P < 0·001)]. Forty-nine discordant cases were re-evaluated; 24 were false positive and 25 false negative. The performance of FCM and frozen sections was also evaluated according to the final histopathological assessment., Conclusions: We found high levels of accuracy for FCM vs. frozen section evaluation in intraoperative BCC margin assessment during Mohs surgery. Some technical issues prevent the wide use of this technique, but new devices promise to overcome these limitations., (© 2018 British Association of Dermatologists.)

Background/objectives: Little is known about the dermoscopic features of atypical fibroxanthoma., Methods: This was a case-control study. Atypical fibroxanthoma lesions were compared with a control group with non-melanoma skin cancer., Results: Altogether 40 atypical fibroxanthoma were collected. Most developed in men (93%), appearing mainly as nodular (63%), amelanotic (93%) and ulcerated (78%) lesions. Most lesions were located on the scalp (55%) and the ears (13%). Dermoscopically, most atypical fibroxanthoma displayed red (83%) and white (70%) structureless areas and irregular linear vessels (43%). A series of features achieved statistical significance when comparing atypical fibroxanthoma with non-melanoma skin cancer. The presence of red and white structureless areas and white lines, and the absence of yellowish-white opaque scales, hairpin vessels and arborising vessels were predictive of atypical fibroxanthoma in univariate analysis. However, when squamous cell carcinoma was excluded from the analysis, none of the criteria achieved statistical significance. When basal cell carcinoma was excluded, three variables achieved statistical significance in predicting atypical fibroxanthoma: red, structureless areas, the absence of opaque yellowish-white scales and absence of white circles., Conclusions: Atypical fibroxanthomas seem to be barely distinguishable from basal cell carcinoma dermoscopically, but they are more easily distinguishable from a well to moderately differentiated squamous cell carcinoma. A histopathological examination is needed for the final diagnosis., (© 2018 The Australasian College of Dermatologists.)

Background: Although several dermoscopic features of in situ melanoma have been identified, data on confocal features of in situ melanoma are still lacking., Objectives: To identify reflectance confocal microscopy (RCM) features of in situ melanoma and to develop a diagnostic score combining dermoscopy and RCM., Methods: In total, 120 in situ melanoma and 213 nevi (test set) were retrospectively analysed to assess the presence of dermoscopic and RCM criteria. Facial and acral lesions were excluded. Spearman's correlation, univariate and multivariate regression models were used to identify features significantly correlated with in situ melanoma diagnosis. Multivariate results on the test set allowed the development of a multistep algorithm, that was tested on a validation set of 100 lesions., Results: The dermoscopic findings of an atypical network and regression were independent predicting factors for in situ melanoma diagnosis [odds ratio (OR) 3·44, 95% CI (confidence interval) 1·70-6·97 and OR 4·17, 95% CI 1·93-9·00, respectively]. Significant confocal predictors for malignancy were epidermal pagetoid spread (OR 2·83, 95% CI 1·32-6·04) and junctional cytological atypia (OR 3·39, 95% CI 1·38-8·30 if focal, OR 8·44, 95% CI 3·21-22·16 if widespread). A multistep diagnostic algorithm able to predict in situ melanoma with a sensitivity of 92·5% and a specificity of 61% was developed. The validation set confirmed the high diagnostic value (sensitivity 92%, specificity 58%)., Conclusions: An easy and reproducible multistep algorithm for in situ melanoma detection is suggested, that can be routinely used in tertiary centres., (© 2018 British Association of Dermatologists.)

Background: Nevi of special sites encompass a class of benign lesions characterized by the presence of atypical clinical and histopathological features that can be difficult to distinguish from melanoma. Dermoscopy and reflectance confocal microscopy may improve the clinical assessment of melanocytic lesions to avoid unnecessary excisions., Objectives: The aim of this study was to assess the value of specific dermoscopic and confocal criteria in distinguishing melanomas from nevi of the breast area., Methods: Dermoscopic and confocal images from consecutive patients with at least one clinically and/or dermoscopically equivocal melanocytic skin lesion of the breast area were retrospectively evaluated. In this case-control study, only histopathologically proven melanomas (cases) and nevi (controls) were included. Spearman's coefficients were first calculated to flag significant correlation; then univariate and multivariate logistic regression analyses were performed to assess which factors were independently associated with the histopathological diagnosis. Finally, a mixed dermoscopic/confocal score was created to distinguish nevi from melanomas on the breast area., Results: The study population included 55 skin lesions of the breast area, 34 (61.8%) nevi and 21 (38.2%) melanomas. Among dermoscopic criteria, atypical network and irregular pigmentation resulted independently associated with melanoma diagnosis (OR: 11.1; 95% CI 1.0-119.9; P:0.048 and OR: 6.5; 95% CI 1.1-37.5; P:0.037, respectively). Furthermore, on RCM examination, the presence of pagetoid cells was an independent positive predictor for melanoma (OR: 38.5; 95% CI 3.9-379.6; P:0.002). The mixed score showed high levels of sensitivity and specificity, 95.2% and 82.4%, respectively, which were higher than dermoscopic and confocal evaluations alone., Conclusion: The combined use of dermoscopy and confocal microscopy in the triage of pigmented lesions of the breast area may help in increasing the diagnostic accuracy and avoiding unnecessary excisions., (© 2017 European Academy of Dermatology and Venereology.)

Importance: The accuracy of melanoma-specific dermoscopic criteria has been tested mainly in studies including invasive tumors. Scarce evidence exists on the usefulness of these criteria for the diagnosis of melanoma in situ (MIS)., Objective: To investigate the diagnostic accuracy of dermoscopic criteria for the diagnosis of MIS., Design, Setting, and Participants: A diagnostic accuracy study with retrospective patient enrollment was conducted in 3 centers specializing in skin cancer diagnosis and management. A total of 1285 individuals with histopathologically diagnosed MIS or other flat, pigmented skin tumors that were histopathologically diagnosed or monitored for at least 1 year were included. Dermoscopic images of MIS and other flat, pigmented skin tumors were evaluated by 3 independent investigators for the presence of predefined criteria. Evaluators were blinded to the clinic dermoscopic and histopathologic diagnosis., Main Outcomes and Measures: Frequencies of dermoscopic criteria per diagnosis were calculated. Crude odds ratios, adjusted odds ratios, and corresponding 95% CIs were calculated by univariate and multivariate logistic regression, respectively., Results: A total of 1285 patients were included in the study (642 [50%] male); mean age was 45.9 years (range, 9-91 years). Of a total of 1285 lesions obtained from these patients, 325 (25.3%) were MIS; 574 (44.7%) were nevi (312 [24.3%] excised and 262 [20.4%] not excised); 67 (5.2%) were seborrheic keratoses, solar lentigines, or lichen planus-like keratoses; 91 (7.1%) were pigmented superficial basal cell carcinomas; 26 (2.0%) were pigmented intraepithelial carcinomas; 100 (7.8%) were Reed nevi; and 102 (7.9%) were invasive melanomas with a Breslow thickness less than 0.75 mm. The most frequent dermoscopic criteria for MIS were regression (302 [92.9%]), atypical network (278 [85.5%]), and irregular dots and/or globules (163 [50.2%]). The multivariate analysis revealed 5 main positive dermoscopic indicators of MIS: atypical network (3.7-fold; 95% CI, 2.5-5.4), regression (4.7-fold; 95% CI, 2.8-8.1), irregular hyperpigmented areas (5.4-fold; 95% CI, 3.7-8.0), prominent skin markings (3.4-fold; 95% CI, 1.9-6.1), and angulated lines (2.2-fold; 95% CI, 1.2-4.1). When compared only with excised nevi, 2 of these criteria remained potent MIS indicators, namely, irregular hyperpigmented areas (4.3-fold; 95% CI, 2.7-6.8) and prominent skin markings (2.7-fold; 95% CI, 1.3-5.7)., Conclusions and Relevance: Clinicians should take into consideration the aforementioned dermoscopic indicators for the diagnosis of MIS.

The reported prevalence of nevus-associated melanoma varies substantially. We performed a systematic review and meta-analysis to determine the incidence and prevalence of this disease; we also performed subanalyses considering age, tumor thickness, and nevus-type classification. In 38 observational cohort and case-control studies, 29.1% of melanomas likely arose from a preexisting nevus and 70.9% de novo. Any given melanoma was 64% less likely to be nevus-associated than de novo (risk ratio 0.36, 95% confidence interval [CI] 0.29-0.44; P < .001; I 2  = 99%); nevus-associated melanomas had a lower mean Breslow thickness than de novo melanomas (mean difference -0.39 mm; 95% CI -0.60 to -0.18; P = .0003; I 2  = 66%). No significant differences were noted regarding the association of nevus-associated melanomas with nondysplastic nevi or dysplastic nevi (risk ratio 0.77, 95% CI 0.49-1.20; P = .24; I 2  = 98%)., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Spitzoid lesions represent a challenging and controversial group of tumours, in terms of clinical recognition, biological behaviour and management strategies. Although Spitz naevi are considered benign tumours, their clinical and dermoscopic morphological overlap with spitzoid melanoma renders the management of spitzoid lesions particularly difficult. The controversy deepens because of the existence of tumours that cannot be safely histopathologically diagnosed as naevi or melanomas (atypical Spitz tumours). The dual objective of the present study was to provide an updated classification on dermoscopy of Spitz naevi, and management recommendations of spitzoid-looking lesions based on a consensus among experts in the field. After a detailed search of the literature for eligible studies, a data synthesis was performed from 15 studies on dermoscopy of Spitz naevi. Dermoscopically, Spitz naevi are typified by three main patterns: starburst pattern (51%), a pattern of regularly distributed dotted vessels (19%) and globular pattern with reticular depigmentation (17%). A consensus-based algorithm for the management of spitzoid lesions is proposed. According to it, dermoscopically asymmetric lesions with spitzoid features (both flat/raised and nodular) should be excised to rule out melanoma. Dermoscopically symmetric spitzoid nodules should also be excised or closely monitored, irrespective of age, to rule out atypical Spitz tumours. Dermoscopically symmetric, flat spitzoid lesions should be managed according to the age of the patient. Finally, the histopathological diagnosis of atypical Spitz tumour should warrant wide excision but not a sentinel lymph-node biopsy., (© 2017 British Association of Dermatologists.)

The literature has not been able to conclude whether pregnancy influences the prognosis of melanoma. The aim of this study was to explore the prognosis of melanoma diagnosed during pregnancy or post partum [pregnancy-associated melanoma (PAM)] compared with melanoma in female patients who were not pregnant. We systematically searched for studies of female patients with melanoma that reported outcomes related to survival. Fifteen eligible studies were found. Overall, PAM was associated with a 17% higher mortality compared with melanoma diagnosed in female patients who were not pregnant (hazard ratio=1.17, 95% confidence interval: 1.03-1.33, P=0.02). The heterogeneity associated with this test was moderate (P=0.07; I=38%). PAM was also associated with a 50% higher recurrence rate compared with melanoma not associated with pregnancy (hazard ratio=1.50, 95% confidence interval: 1.19-1.90, P<0.001). The heterogeneity associated with this test was low (P=0.69; I=0%). A limitation of this meta-analysis is the definition of PAM, which is not unanimous among the studies included. Our results indicate that PAM is associated with a worse prognosis than melanoma not related to pregnancy, both in terms of overall survival and disease-free survival. On the basis of our data, we anticipate that the survival difference we report here will be further amplified with the addition of future well-carried out studies. We suggest that detection of PAM requires particular awareness by healthcare professionals.

Importance: Reflectance confocal microscopy (RCM) improves diagnostic accuracy in skin cancer detection when combined with dermoscopy; however, little evidence has been gathered regarding its real impact on routine clinical workflow, and, to our knowledge, no studies have defined the terms for its optimal application., Objective: To identify lesions on which RCM performs better in terms of diagnostic accuracy and consequently to outline the best indications for use of RCM., Design, Setting, and Participants: Prospectively acquired and evaluated RCM images from consecutive patients with at least 1 clinically and/or dermoscopically equivocal skin lesion referred to RCM imaging, from January 2012 to October 2014, carried out in a tertiary referral academic center., Main Outcomes and Measures: A total of 1279 equivocal skin lesions were sent for RCM imaging. Spearman correlation, univariate, and multivariate regression models were performed to find features significantly correlated with RCM outcome., Results: In a total of 1279 lesions in 1147 patients, RCM sensitivity and specificity were 95.3% and 83.9%, respectively. The number of lesions needed to excise to rule out a melanoma was 2.4. After univariate and multivariate regression analysis, head and neck resulted as the most appropriate body location for confocal examination; RCM showed a high diagnostic accuracy for lesions located on sun-damaged skin (adjusted odds ratio [aOR], 2.13; 95% CI, 1.37-3.30; P=.001) and typified by dermoscopic regression (aOR, 2.13; 95% CI, 1.31-3.47; P=.002) or basal-cell carcinoma specific criteria (aOR, 9.35; 95% CI, 1.28-68.58; P=.03)., Conclusions and Relevance: Lesions located on the head and neck, damaged by chronic sun-exposure, and dermoscopically typified by regression represent best indications for the use of RCM.

Background: Dermoscopy is limited in differentiating accurately between pigmented lentigo maligna (LM) and pigmented actinic keratosis (PAK). This might be related to the fact that most studies have focused on pigmented criteria only, without considering additional recognizable features., Objectives: To investigate the diagnostic accuracy of established dermoscopic criteria for pigmented LM and PAK, but including in the evaluation features previously associated with nonpigmented facial actinic keratosis., Methods: Retrospectively enrolled cases of histopathologically diagnosed LM, PAK and solar lentigo/early seborrhoeic keratosis (SL/SK) were dermoscopically evaluated for the presence of predefined criteria. Univariate and multivariate regression analyses were performed and receiver operating characteristic curves were used., Results: The study sample consisted of 70 LMs, 56 PAKs and 18 SL/SKs. In a multivariate analysis, the most potent predictors of LM were grey rhomboids (sixfold increased probability of LM), nonevident follicles (fourfold) and intense pigmentation (twofold). In contrast, white circles, scales and red colour were significantly correlated with PAK, posing a 14-fold, eightfold and fourfold probability for PAK, respectively. The absence of evident follicles also represented a frequent LM criterion, characterizing 71% of LMs., Conclusions: White and evident follicles, scales and red colour represent significant diagnostic clues for PAK. Conversely, intense pigmentation and grey rhomboidal lines appear highly suggestive of LM., (© 2015 British Association of Dermatologists.)

Background: Ultraviolet radiation plays an important role in the pathogenesis of non-melanoma skin cancer. Outdoor workers, including farmers, experience higher exposure levels compared to the general population. Available literature data suggest that occupational ultraviolet exposure represents an independent risk factor for squamous cell carcinoma; whereas for basal cell carcinoma (BCC) this association still remains unclarified., Objectives: To analyse the epidemiological, clinical and histological data of patients diagnosed with BCC, and correlate them with outdoor occupation in farmers., Methods: Individuals with histologically diagnosed BCCs, between September 2013 and September 2015, were included in the study. Their medical data, including epidemiological, clinical and histological characteristics, were recorded and analysed in conjunction with the occupation. Farmers were identified based on their specific public health insurance., Results: Three hundred and forty patients, with 542 BCCs were included in the study. One hundred and twenty (35.3%) were farmers. Mean age of farmers was lower than non-farmers (66.0 ± 9.1 years vs. 75 ± 6.6 years, Mann-Whitney U-test, P < 0.001). Farmers had a sixfold higher probability for exhibiting photodamaged skin (OR = 6.02, 95% CI: 3.66-9.90, P < 0.001). Farmer workers were more likely to exhibit infiltrative or morpheaform BCC, but less likely to develop superficial BCC., Conclusion: Our results indicate a higher risk of earlier development of more aggressive histological subtypes of BCCs in farmers. Photodamage was also more common in this group. Primary and secondary prevention strategies focusing on outdoor workers, including farmers, are mandatory., (© 2016 European Academy of Dermatology and Venereology.)

Background: Radiotherapy is an established treatment for some types of patients with nonmelanoma skin cancer. A hypofractionated schedule has been proposed as a valuable option for elderly disabled patients to minimize the number of hospital visits., Objective: We sought to compare a weekly hypofractionated orthovoltage radiotherapy regimen with a standard daily one for the treatment of nonmelanoma skin cancer., Methods: A retrospective cohort study was performed on 436 tumors. Overall survival, disease-free survival, and cosmetic outcome were measured. Life-table analysis, Kaplan-Meier survival analysis, and multivariate Cox regression model were performed., Results: The hypofractionated regimen was not associated with increased recurrence rates and mortality, or with a poorer cosmetic outcome, when compared with the daily schedule., Limitations: Absence of complete information about acute treatment toxicity and a shorter follow-up time for patients receiving the weekly schedule are limitations of this study., Conclusions: A weekly hypofractionated regimen of orthovoltage radiotherapy seems to be the most appropriate approach in elderly disabled patients with nonmelanoma skin cancers., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Epidemiological and clinical data suggest that actinic damage to the skin is an important predictor of skin carcinogenesis., Aim: To investigate the association of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with sun-damage alterations seen by histopathology., Method: In the current prospective study, perilesional skin of SCC or BCC lesions was evaluated for presence of alterations associated with chronic photodamage. Presence of scarring, perineural/perivascular invasion, haemorrhage/haemorrhagic crust, ulceration/erosion and margin involvement were also assessed., Result: Of 6038 included lesions, 4523 (74.9%) were BCCs and 1515 (25.1%) were SCCs. Presence of actinic damage was five times more frequent in SCC than in BCC (OR = 5.29, 95% CI 4.44-6.00, P < 0.001), and diagnosis of SCC was twice as common in photo-exposed than nonphoto-exposed body sites (OR = 2.34, 95% CI 2.03-2.70, P < 0.001). There were twofold higher odds for actinic damage in SCC compared with Bowen disease (OR = 2.015, 95% CI 1.55-2.61, P < 0.001). Assessing the different BCC histological subtypes, we found that nodular BCC had at least twofold higher odds (OR = 2.63, 95% CI 2.09-3.32), infiltrative BCC had 48% higher odds (OR = 1.487, 95% CI 1.18-1.87) and basosquamous BCC had fourfold higher odds (OR = 4.10, 95% CI 3.01-5.57) of having actinic damage compared with superficial BCC., Conclusions: Histological verification of ultraviolet-associated alterations in the perilesional skin in patients with NMSC in our study confirms the aetiopathogenic link between sun exposure and epithelial carcinogenesis on a histopathological basis. This correlation was stronger for SCCs than for BCCs., (© 2015 British Association of Dermatologists.)

Background: Melanosis is the most common cause of mucosal pigmentation and can be clinically difficult to differentiate from early melanoma (MM). Dermoscopy can help in the distinction between melanosis and MM, but in some instances, melanoses may exhibit overlapping features with MM such as the presence of grey colour., Objective: We sought to evaluate whether reflectance confocal microscopy (RCM) can help to better understand the dermoscopic features of melanoses in order to assist clinicians in their diagnosis., Methods: All melanoses diagnosed between June 2011 and December 2014 in the Departments of Dermatology of the University of Saint-Etienne (France) and of Modena and Reggio Emilia (Italy), for which dermoscopic and RCM images were available, were included. Twenty-two lesions were biopsied to confirm the clinical diagnosis, whereas the others did not present any change at a follow-up of at least 6 months. The correlation between dermoscopic and RCM features were evaluated by the Spearman's rho correlation coefficient., Results: 55 melanoses were studied: 31 of the oral mucosa and 24 of the genital mucosa. 49% (n = 27) of melanoses exhibited a grey colour under dermoscopy. The grey colour correlated with the presence of melanophages under RCM (ρ = 0.424, P = 0.002)., Conclusion: Our findings highlight that the presence of the grey colour on dermoscopy, considered as an alerting feature, is common in melanoses and it is related to the presence of melanin-laden inflammatory cells in the papillary dermis on RCM. When it is present as a 'pure' feature not associated to other colours than brown or to atypical dermoscopical structures, it could be related to the diagnosis of melanosis., (© 2015 European Academy of Dermatology and Venereology.)

Background: Dermoscopically, one of the most common findings in melanocytic lesions is a globular pattern. A regular globular pattern is a common finding in naevi. Melanoma can also show a globular pattern, with globules typically irregular in size, colour and distribution., Objectives: To investigate the likelihood of diagnosing melanoma according to distinct dermoscopic and confocal aspects., Methods: Dermoscopic and confocal aspects of 83 excised melanocytic lesions dermoscopically showing globules were analysed., Results: Our study population included 39 acquired melanocytic naevi, 16 Spitz naevi and 28 melanomas. Univariate analysis showed that regular distribution of globules on dermoscopy is associated with a ninefold lower risk for melanoma, whereas an irregular distribution is associated with an almost 10-fold increased risk for melanoma. Concerning confocal features, dense nests are associated with a fivefold lower risk for melanoma, whereas loosely arranged nests are associated with an almost sixfold risk for melanoma; moreover, the presence of round cells is associated with a 17-fold lower risk for melanoma, whereas pleomorphic cells are associated with an almost 16-fold risk for melanoma., Conclusions: So that melanoma is not missed, clinicians should carefully analyse globular lesions in adults, focusing, in particular, on the distribution of globules and on the presence of confocal cytological atypia., (© 2015 British Association of Dermatologists.)

Background: Few studies have described the clinical and dermoscopic features of atypical Spitz tumors., Objective: We sought to describe the clinical and dermoscopic features of a series of atypical Spitz tumors as compared with those of conventional Spitz nevi., Methods: This was a multicenter, retrospective, case-control study, analyzing the clinical and dermoscopic characteristics of 55 atypical Spitz tumors and 110 Spitz nevi that were excised and diagnosed histopathologically., Results: The majority of atypical Spitz tumors presented clinically as a plaque or nodule, dermoscopically typified by a multicomponent or nonspecific pattern. A proportion of lesions (16.4%) exhibited the typical nonpigmented Spitzoid pattern of dotted vessels and white lines under dermoscopy. Nodularity, ulceration, linear vessels, polymorphic vessels, white lines, and blue-white veil were associated with atypical Spitz tumors by univariate analysis, but only nodularity and white lines remained significant after multivariate analysis. In contrast, a pigmented typical Spitzoid pattern was a potent predictor of Spitz nevi, associated with 6.5-fold increased probability., Limitations: Differentiation from Spitzoid melanoma and other nonmelanocytic lesions was not investigated., Conclusion: Atypical Spitz tumors are polymorphic melanocytic proliferations with a nodular clinical appearance. Dermoscopically they demonstrate a multicomponent and nonspecific pattern. A typical nonpigmented Spitzoid pattern on dermoscopy (with dotted vessels and white lines) does not exclude atypical Spitz tumors., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The parallel ridge pattern (PRP) is considered the dermoscopic hallmark of acral melanoma (AM). However, it was recently shown that approximately one-third of AMs do not display a PRP dermoscopically, rendering their detection more troublesome., Objectives: To investigate the diagnostic accuracy of dermoscopic criteria for the diagnosis of AM., Methods: Dermoscopic images of consecutive cases of histopathologically diagnosed AMs and acral naevi with histopathological diagnosis or with at least 1 year of follow-up were evaluated by three independent investigators for the presence of predefined criteria. Crude and adjusted odds ratios and their corresponding 95% confidence intervals were calculated by univariate and multivariate logistic regression, respectively. Receiver operating characteristic curves were used to choose among competing classification schemes., Results: In total 603 lesions (472 naevi and 131 AMs) were included in the study. A scoring system (named BRAAFF) composed of six variables was associated with optimal area under the curve and sensitivity for the diagnosis of AM. This method includes four positive (irregular blotches, ridge pattern, asymmetry of structures and asymmetry of colours) and two negative predictors (furrow pattern and fibrillar pattern)., Conclusions: The BRAAFF checklist significantly improves the diagnostic accuracy of dermoscopy for the diagnosis of AM., (© 2015 British Association of Dermatologists.)

Background: The clinical and histopathological diagnosis of skin tumours arising on the face may be challenging., Objective: An improved knowledge about the age-related patterns of facial skin tumours may aid the correct diagnosis and management., Methods: We conducted a prospective, cross-sectional morphological study to investigate the age-related frequency and morphological variability in facial skin tumours in a cohort of consecutive subjects attending two skin lesion clinics in Italy between June and September 2011. A total of 454 consecutive subjects (249 women; 55.5%) presenting with a total of 1866 facial tumours were enrolled in the study. Of the entire cohort, 54 (11.9%) subjects had no facial lesion., Results: Total body naevus count correlated significantly with the mean number of facial lesions (ρ = 0.289, P < 0.001). The majority of flat lesions were pigmented (1056; 75.70%), compared to palpable (233; 17.40%) and raised lesions (93; 6.90%), the association being statistically significant (Pearson's chi square, P < 0.001. Considering melanocytic tumours only, the frequency of flat lesions significantly decreased with increasing age, while the number of palpable and raised lesions increased with increasing age (chi-square, P < 0.001). This trend was mainly due to naevi, whereby pigmented melanocytic naevi decreased with increasing age. Conversely, the percentage of non- pigmented naevi increased with increasing age (chi-square, P < 0.001)., Limitations: The study was conducted in skin lesion clinics in Italy, thus any general conclusions with respect to common traits or features based on the phenotypic and genetic diversity within the European population cannot be stated., Conclusions and Relevance: Our study suggests that a high number of facial naevi could predict a high total naevus count. Moreover, naevi present a different morphological appearance during lifetime being initially flat, small and pigmented and becoming later raised, large and hypopigmented. Instead, lentigo maligna is an intraepidermal proliferation that typically presents as flat, large pigmented macule. A given histopathological diagnosis of a junctional naevus of a flat, facial pigmented macule of an elderly should be critically reviewed and treated with caution., (© 2014 European Academy of Dermatology and Venereology.)

Background: Melanoma is the leading cause of skin cancer-associated mortality. The vast majority of newly diagnosed melanomas are confined to the primary cutaneous site. Surgery represents the mainstay of melanoma treatment. Treatment strategies include wide excision of the primary tumour and sentinel lymph node biopsy (SLNB) to assess the status of the regional nodal basin(s). SLNB has become an important component of initial melanoma management providing accurate disease staging., Objectives: To assess the effects and safety of SLNB followed by completion lymph node dissection (CLND) for the treatment of localised primary cutaneous melanoma., Search Methods: We searched the following databases up to February 2015: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2015, Issue 1), MEDLINE (from 1946), EMBASE (from 1974), and LILACS ((Latin American and Caribbean Health Science Information database, from 1982). We also searched the following from inception: African Index Medicus, IndMED of India, Index Medicus for the South-East Asia Region, and six trials registers. We checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials (RCTs). We searched ISI Web of Science Conference Proceedings from inception to February 2015, and we scanned the abstracts of major dermatology and oncology conference proceedings up to 2015., Selection Criteria: Two review authors independently assessed all RCTs comparing SLNB followed by CLND for the treatment of primary localised cutaneous melanoma for inclusion. Primary outcome measures were overall survival and rate of treatment complications and side effects., Data Collection and Analysis: Two review authors independently extracted and analysed data on survival and recurrence, assessed risk of bias, and collected adverse effect information from included trials., Main Results: We identified and included a single eligible trial comparing SLNB with observation and published in eight different reports (from 2005 to 2014) with 2001 participants. This did not report on our first primary outcome of overall survival. The study did report on the rate of treatment complications. Our secondary outcomes of disease-specific and disease-free survival, local recurrence and distant metastases were reported. There were 1347 participants in the intermediate-thickness melanoma group and 314 in the thick melanoma group.With regard to treatment complications, short-term surgical morbidity (30 days) in 1735 participants showed no difference between SLNB and observation (risk ratio [RR] 1.11; 95% confidence interval [CI] 0.9 to 1.37) for wide excision of the tumour site but favoured observation for complications related to the regional nodal basin (RR 14.36; 95% CI 6.74 to 30.59).The study did not report the actual 10-year melanoma-specific survival rate for all included participants. Instead, melanoma-specific survival rates for each group of participants: intermediate-thickness melanoma (defined as 1.2 to 3.5 mm) and thick melanomas (defined as 3.50 mm or more) was reported.In the intermediate-thickness melanoma group there was no statistically significant difference in disease-specific survival between study groups at 10 years (81.4 ± 1.5% versus 78.3 ± 2.0%, hazard ratio [HR] 0.84; 95% CI 0.65 to 1.09). In the thick melanoma group, again there was no statistically significant difference in disease-specific survival between study groups at 10 years (58.9.3 ± 4.1% versus 64.4 ± 4.6%, HR 1.12; 95% CI 0.77 to 1.64). Combining these groups there was some heterogeneity (I² = 34%) but the total HR was not statistically significant (HR 0.92; 95% CI 0.74 to 1.14). This study failed to show any difference for its stated primary outcome.The summary estimate for disease-free survival at 10 years favoured SLNB over observation in participants with intermediate-thickness and thick melanomas (HR 0.75; 95% CI 0.63 to 0.89).With regard to the rate of local and regional recurrence as the site of first recurrence, a benefit of SLNB uniformly existed in both groups of participants with intermediate-thickness and thick melanomas (RR 0.56; 95% CI 0.45 to 0.69). This is in contrast with a uniformly unfavourable effect of SLNB with regard to the rate of distant metastases as site of first recurrence, in both groups of participants with intermediate-thickness and thick melanomas (HR 1.33; 95% CI 1.03 to 1.72)., Authors' Conclusions: We contacted the trial authors querying the lack of data on overall survival which was the primary outcome of their important study. They stated "there are numerous additional analyses that have yet to be reported for the trial". We expect that overall survival data will be available in a future update of this review.Disease-free survival and rate of local and regional recurrence favoured SLNB in both groups of participants with intermediate-thickness and thick melanomas but short-term surgical morbidity was higher in the SLNB group, especially with regard to complications in the nodal basin.The evidence for the outcomes of interest in this review is of low quality due to the risk of bias and imprecision of the estimated effects. Further research may have an important impact on our estimate of the effectiveness of SLNB in managing primary localised cutaneous melanoma. Currently this evidence is not sufficient to document a benefit of SLNB when compared to observation in individuals with primary localised cutaneous melanoma.

Background: Dermoscopy improves the recognition of melanoma and Spitz nevus but occasionally melanoma may exhibit a symmetric pattern mimicking Spitz nevus., Objective: We sought to investigate the likelihood of finding melanoma when excising a symmetric Spitzoid-looking lesion in patients aged 12 years or older., Methods: This study included patients aged 12 years or older with symmetric, Spitzoid-looking lesions that were diagnosed histopathologically as Spitz nevus or melanoma. Demographic, clinical, and dermoscopic variables were included in the analysis. We used χ(2) for nonparametric comparisons. Crude odds ratios and 95% confidence intervals were calculated by univariate logistic regression., Results: Of 384 included lesions, 333 (86.7%) were histopathologically diagnosed as Spitz nevus and 51 (13.3%) as melanoma. The risk of melanoma significantly increased with increasing age, being 50% or higher after the age of 50 years., Limitations: Limitations are retrospective design, exclusion of patients younger than 12 years, lack of detailed histopathologic data, and limited sample size., Conclusion: Our results confirm the observation that melanoma may be dermoscopically indistinguishable from Spitz nevi, strongly suggesting that the only safe strategy not to miss melanoma is to excise all Spitzoid-looking lesions in patients aged 12 years or older., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)