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Summary: Background: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front‐line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF). Objectives: To identify (i) differences in first‐line approaches according to tumour‐nodes‐metastasis‐blood (TNMB) staging; (ii) parameters related to a first‐line systemic approach and (iii) response rates and QoL measures. Methods: In total, 395 newly diagnosed patients with early‐stage MF (stage IA–IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. Results: The most common first‐line therapy was skin‐directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA–IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first‐line SDT was 73%, while the ORR to first‐line systemic treatments was lower (57%) (P = 0·027). Health‐related QoL improved significantly both in patients with responsive disease and in those with stable disease. Conclusions: Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early‐stage MF need to address these issues. What is already known about this topic? Early‐stage mycosis fungoides is characterized by a good prognosis.The first‐line treatment approach is typically stage based and is usually skin‐directed therapy. What does this study add? This multicentre prospective international study reports that real‐life treatment decisions are not limited to a stage‐based approach but are also influenced by the presence of plaques and folliculotropic mycosis fungoides.Approximately half of the patients with early‐stage disease experienced a moderate or severe impact on their quality of life at diagnosis.This study suggests that treatment guidelines in patients with early‐stage disease should incorporate high‐risk features and quality‐of-life evaluation. Linked Comment: Porcu and Nikbakht. Br J Dermatol 2021; 184:594–595. [ABSTRACT FROM AUTHOR]

Summary: Background: Naevi number changes with age. Thus, a better understanding of naevus biology will shed more light on the genetic and environmental factors involved in melanoma development. Objectives: To use a two‐wave study to better understand the evolution of naevi in healthy adults. Methods: This study is a prospective two‐wave study based on adult twins from the TwinsUK registry (n = 414) who underwent total body naevus counts with an interval of at least 15 years. A negative binomial hierarchical model with two levels, the individual and the twin pair, was used to estimate expected changes in naevus count between the first and second visit, at any specific body site and on the whole body. The model was adjusted for age, calendar year at the first visit, height and skin type. Results: The mean age of participants was 46 years at the first visit and 63 years at the second visit (the mean elapsed time between visits was 17 years). An increase in naevus count was observed in 235 (57%) participants and a decrease was observed in 166 (40%). The mean difference in total naevus count between the two visits was nine. The expected total body naevus count increased, on a logarithmic scale, by 0·28 [95% confidence interval (CI) 0·16–0·40] with a change in the incidence rate of total body naevus count of 32% (95% CI 17–49%). However, the observed increase in naevus count over time was observed only on the upper parts of the body, whereas there was no evidence of an increase on the lower parts. Conclusions: Naevus counts increased slightly over time at older ages, but this was dependent on body site. The overall decrease in naevus counts previously reported in cross‐sectional studies has not been confirmed by this longitudinal study. What is already known about this topic? Naevus counts change during a lifetime according to cross‐sectional studies, with a decreasing naevus count from adulthood onwards. What does this study add? This two‐wave study suggests that naevus counts increased slightly over time in participants at older ages; however, this was dependent on body site.A decrease in naevus counts reported in cross‐sectional studies has not been confirmed by this longitudinal study.A decrease in naevus count may occur at an earlier age than the age groups included in our study; other studies collecting longitudinal naevus data with similar protocols may need to include younger individuals.Misclassification of naevi as solar lentigines is also a possible explanation for this increase, as the rise was seen on sun‐exposed sites. Linked Comment: Cust. Br J Dermatol 2021; 184:193. [ABSTRACT FROM AUTHOR]

Summary: Background: The presence of ulceration has been recognized as an adverse prognostic factor in primary cutaneous melanoma (PCM). Objectives: To investigate whether the extent of ulceration (EoU) predicts relapse‐free survival (RFS) and overall survival (OS) in PCM. Materials and methods: We retrieved data for 477 patients with ulcerated PCM from databases of the Italian Melanoma Intergroup. Univariate and multivariable Cox proportional hazard models were used to assess the independent prognostic impact of EoU. Results: A significant interaction emerged between Breslow thickness (BT) and EoU, considering both RFS (P < 0·0001) and OS (P = 0·0006). At multivariable analysis, a significant negative impact of EoU on RFS [hazard ratio (HR) (1‐mm increase) 1·26, 95% confidence interval (CI) 1·08–1·48, P = 0·0047] and OS [HR (1‐mm increase) 1·25, 95% CI 1·05–1·48, P = 0·0120] was found in patients with BT ≤ 2 mm, after adjusting for BT, age, tumour‐infiltrating lymphocytes, sentinel lymph node status and mitotic rate. No impact of EoU was found in patients with 2·01–4 mm and > 4 mm BT. Conclusions: This study demonstrates that EoU has an independent prognostic impact in PCM and should be recorded as a required element in pathology reports. What is already known about this topic? Ulceration is a well‐known prognostic factor in melanoma.There are conflicting results on the prognostic value of the extent of ulceration. What does this study add? The extent of ulceration is an independent prognostic factor in primary cutaneous melanoma with Breslow thickness (BT) ≤ 2 mm.The extent of ulceration should be incorporated into the pathology report as a required, core element.Patients with extensive ulceration with a BT ≤ 2 mm are at high risk of recurrence and should be included in prospective adjuvant trials. Linked Comment: Wilkinson and Gyorki. Br J Dermatol 2021; 184:192–193. [ABSTRACT FROM AUTHOR]

Summary: Background: Ex vivo confocal microscopy (CM) works under two modes, fluorescence and reflectance, allowing the visualization of different structures. Fluorescence CM (FCM) requires a contrast agent and has been used for the analysis of basal cell carcinomas (BCCs) during Mohs surgery. Conversely, reflectance CM (RCM) is mostly used for in vivo diagnosis of equivocal skin tumours. Recently, a new, faster ex vivo confocal microscope has been developed which simultaneously uses both lasers (fusion mode). Objectives: To describe the BCC features identified on reflectance, fluorescence and fusion modes using this novel device. To determine the best mode to identify characteristic BCC features. To develop a new staining protocol to improve the visualization of BCC under the different modes. Methods: From September 2016 to June 2017, we prospectively included consecutive BCCs which were excised using Mohs surgery in our department. The lesions were evaluated using ex vivo CM after routine Mohs surgery. The specimens were first stained with acridine orange and then stained using both acetic acid and acridine orange. Results: We included 78 BCCs (35 infiltrative, 25 nodular, 12 micronodular, 6 superficial). Most features were better visualized with the fusion mode using the double staining. We also identified new CM ex vivo features, dendritic and plump cells, which have not been reported previously. Conclusions: Our results suggest that nuclei characteristics are better visualized in FCM but cytoplasm and surrounding stroma are better visualized in RCM. Thus, the simultaneous evaluation of reflectance and fluorescence seems to be beneficial due to its complementary effect. What's already known about this topic? Ex vivo fluorescent confocal microscopy (FCM) is an imaging technique that allows histopathological analysis of fresh tissue.FCM is faster – at least one‐third of the time – than conventional methods.FCM has a sensitivity of 88% and a specificity of 99% in detecting basal cell carcinomas (BCCs). What does this study add? Reflectance and fluorescence modes can be used simultaneously in a new ex vivo CM device.Each mode complements the other, resulting in an increase in the detection of BCC features in fusion mode.A combined staining using acetic acid and acridine orange enhances the visualization of tumour and stroma without damaging the tissue for further histopathological analysis. Linked Editorial: Navarrete‐Dechent et al. Br J Dermatol 2020; 182:257–259. Plain language summary available online [ABSTRACT FROM AUTHOR]

Dear Editor, Dupilumab, an inhibitor of interleukin (IL)-4/13 activity, is a biological agent approved for the treatment of moderate-to-severe atopic dermatitis (AD).1 In this study, we aimed to assess the long-term effectiveness and safety of dupilumab in a real-world clinical setting. Primary effectiveness outcomes included the proportion of patients at week 52 achieving EASI improvements of 50%, 75% or 90% (EASI 50, EASI 75 or EASI 90). Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS). [Extracted from the article]

Summary: The prognostic significance of histological regression in primary melanoma has been debated for many years. We aim to review the evidence to see how histological regression may affect prognosis. A systematic review was performed by searching in MEDLINE, Scopus and the Cochrane Library from 1 January 1966 to 1 August 2015. All studies reporting hazard ratios or data on survival and histological regression were included. Primary random‐effects meta‐analyses were used to summarize outcome measures. Heterogeneity was assessed using the χ2‐test and I2‐statistic. To assess the potential bias of small studies we used funnel plots and the Begg and Mazumdar adjusted rank correlation method. Summaries of survival outcomes were measured as hazard ratios or relative risk of death at 5 years according to the presence of histological regression of primary melanoma. In total, 183 articles were reviewed out of 1876 retrieved. Ten studies comprising 8557 patients were included. Patients with histological regression had a lower relative risk of death (0·77, 95% confidence interval 0·61–0·97) than those without. Examination of the funnel plot did not provide evidence of publication bias. The results showed that histological regression is a protective factor for survival. [ABSTRACT FROM AUTHOR]

Background Despite recent discoveries of germline and somatic mutations in melanoma, naevus count remains the most important risk factor for melanoma. Counting naevi on the whole body is time consuming. In order to identify patients at risk for melanoma, many studies have used naevus count on selected body sites as a proxy for total body naevus count ( TBNC). Objectives The main aim of this study was to assess the predictive value of naevus count on 17 different body sites in estimating TBNC in a large cohort of healthy U.K. Caucasian female subjects. Once the site with the best predictive value for TBNC was determined, a second aim was to estimate the cut-off values of naevus counts at this anatomical site that best predict the presence of 50 or 100 naevi, respectively. Methods The most predictive body site for TBNC was assessed in a cohort of healthy female twins. This finding was replicated on a control group from a U.K. case-control study and a prediction model was performed afterwards. The area under the receiver operating characteristics curve was used to evaluate the best cut-off for the prediction of having a TBNC of more than 50 or 100. Results There were 3694 female twins included. The TBNC showed a steady decline after the age of 30 years ( P < 0·001). The most predictive sites for TBNC were the arms and legs: the adjusted correlation coefficients were 0·50 and 0·51 ( P < 0·001) for the right and left arm, respectively, and 0·49 and 0·48 for the right and left legs, respectively ( P < 0·001). The arm remained the most predictive site for TBNC when replicated in a control population including both sexes. In the twin study, women with more than 11 naevi on the right arm were approximately nine times more likely to have more than 100 naevi (odds ratio = 9·38, 95% confidence interval 6·71-13·11). Conclusions The ability to estimate TBNC quickly by counting naevi on one arm could be a very useful tool in assessing melanoma risk in primary care. [ABSTRACT FROM AUTHOR]

The article focuses on a study which analyzes the dermoscopic and reflectance confocal microscopy (RCM) changes in vivo observed over time during the sequential follow-up of a series of Spitz naevi (SNs). Topics discussed include the study samples of lesions clinically and dermoscopically diagnosed as SN, the presence of sharp demarcation on most of the lesions, and the presence of pagetoid infiltration at the time of the first evaluation.

Background The prognostic significance of regression in primary melanoma has been debated over the past few years. Once it was considered to be a negative prognostic factor, as it may have prevented proper melanoma thickness measurement, therefore affecting the staging of the tumours. For this reason, it was considered to be an indication for sentinel lymph node biopsy ( SLNB) in melanoma < 1 mm. Objectives To ascertain the utility of SLNB in thin melanoma and to clarify the role of regression in disease-free survival ( DFS) and overall survival ( OS) in our series. Methods We analysed data collected from 1693 consecutive patients with AJCC (American Joint Committee on Cancer) stage I-II melanoma. Results Globally, SLNB was performed in 656 out of 1693 patients. Regression was present in 349 patients and 223 of them were characterized by thin lesions. SLNB was performed in 104 cases of thin melanoma with regression. The majority of regional lymph node metastases were observed in patients who did not undergo SLNB (89 out of 132). Among the remaining 43 'false negative' patients only three showed regression in the primary. Using the Cox multivariate model, histological regression maintained a significant protective role [hazard ratio ( HR) 0·62, P = 0·012 for DFS; HR 0·43, P = 0·008 for OS] when corrected for the principal histopathological and clinical features, despite SLNB. Conclusions We confirmed that regression alone should not be a reason to perform SLNB in thin melanoma and, on the contrary, it can be considered a favourable prognostic factor in patients with AJCC stage I-II melanoma. [ABSTRACT FROM AUTHOR]

Median canaliform nail dystrophy of Heller in a patient with atopic dermatitis: "miraculous" healing with dupilumab Median canaliform dystrophy of Heller is a relatively rare nail abnormality characterized by central single longitudinal split with an inverted fir-tree pattern, which commonly involves the thumbnails, and rarely other fingernails.[1] The pathogenesis is not entirely clear; the most common hypothesis is repetitive trauma to the proximal nail fold and the underlying nail matrix, also self-induced, or compression by subungual tumours. We report a patient in whom nail dystrophy resolved following resolution of pruritus with dupilumab, given for severe AD. [Extracted from the article]

Linked Article: Duffy et al. Br J Dermatol 2019; 181:1009–1016. [ABSTRACT FROM AUTHOR]

Linked Article: Pérez‐Anker et al. Br J Dermatol 2020; 182:468–476 [ABSTRACT FROM AUTHOR]

Summary: Ex vivo (meaning that it takes place outside the body) confocal microscopy is an imaging technique which allows scientists to look at samples of skin that have been removed by biopsy (where a small tissue sample is removed surgically), and it is often used to diagnose skin cancers including basal cell carcinomas (BCC). There are two main types, fluorescence confocal microscopy (FCM) and reflectance confocal microscopy (RCM), allowing the visualization of different structures in the tissue sample. FCM requires a stain, a type of dye, to be added to the sample and has been used for the analysis of BCC during a type of surgery called Mohs micrographic surgery (MMS). MMS involves removing a thin layer of the tumour at a time with a very small margin of healthy skin around it, and each layer is immediately checked under the microscope. In RCM, a beam of light is focused on a small area of skin. Varying amounts of this light are reflected back depending on the structure of the cells. This creates a grey‐scale image of a section of the skin which allows doctors to see abnormalities. Recently, a new, faster ex vivo confocal microscope has been developed which uses reflectance and fluorescence simultaneously, providing high‐resolution images in both modes separately and in combination (fusion mode). In this study, the researchers, from Spain, explain which features of a BCC are seen using each of the methods, and if one of the methods is better than the others. They also wanted to develop a new staining protocol to improve the visualization of BCC under the different modes. The researchers used BCCs which were excised (removed) using Mohs surgery in their department. The specimens were first stained with acridine orange and then stained using both acetic acid and acridine orange. Most features were better visualized with the fusion mode using double staining. They also identified new ex vivo confocal microscopy features, dendritic and plump cells, which have not been previously reported. Their results suggest that some features (nuclei characteristics) are better visualized in FCM but others (cytoplasm and surrounding stroma) are better visualized in RCM. For this reason, using both reflectance and fluorescence at the same time, using fusion mode, seems to be beneficial. This summary relates to the study: Basal cell carcinoma characterization using fusion ex vivo confocal microscopy: a promising change in conventional skin histopathology Linked Article: Pérez‐Anker et al. Br J Dermatol 2020; 182:468–476 [ABSTRACT FROM AUTHOR]

The article examines the effects of naevus body distribution and melanoma risk in two melanoma case-control studies in Great Britain and Australia. Topics discussed include a comparison of body-site mean naevus counts according to sex, logistic regression on melanoma risk based on numbers of naevi according to sex, and high incidence of naevi on the trunk in men.

The article describes the utility of dermoscopy and reflectance confocal microscopy (RCM) in evaluating the full regression of skin metastases after BRAF inhibitor therapy in a woman in her 50s who has a ductal infiltrating carcinoma at her right breast. Topics discussed include the typified nodules and papules and the presence of bluish colour with crystalline structures and peppering features observed during dermoscopy and the scar-like collagen with few inflammatory cells revealed by RCM.

The authors discuss the heritability aspects of naevus pattern. Topics include the environmental and genetic factors of naevus morphology, the association of heritability rate with the distribution of naevus at sun-exposed areas, and a study regarding the differences in particular naevus dermoscopic traits between dizygotic (DZ) and monozygotic (MZ) twins.