Objective To detect a detrimental or beneficial effect of anti‐IL‐12/23 biological agents (ustekinumab and briakinumab) for the treatment of chronic plaque psoriasis on major adverse cardiovascular ...events (MACEs).
Design Systematic review and meta‐analysis MEDLINE, EMBASE, the Cochrane Skin Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, SciVerse Scopus and ongoing trial registries were searched from inception until December 2011. Search strategy, eligibility criteria, data and statistical analysis methods were defined prior to the literature search. Randomized, placebo‐controlled, double‐blind, monotherapy studies with safety data for MACEs of IL‐12/23 antibodies in adults were eligible for inclusion. Studies of psoriatic arthritis were excluded. Information from each study was extracted independently by two reviewers, using a standardized data extraction form. The primary outcome measure was the number of MACEs during the placebo‐controlled phase of treatment.
Results MACEs include myocardial infarction, cerebrovascular accident or cardiovascular death. No statistical heterogeneity across the studies using the I2 statistic (I2 = 0) was found. We employed Peto one‐step method to determine odds ratios and quantify a possible detrimental or beneficial association of IL‐12/23 antibodies treatment with MACEs. We found a possible higher risk of MACEs in those patients treated with IL‐12/23 antibodies compared with those at placebo (OR = 4.23, 95% CI: 1.07–16.75, P = 0.04). This study is unaffected by non‐reporting of outcomes with no events.
Conclusion Compared with placebo, there was a significant difference in the rate of MACEs observed in patients receiving anti‐IL‐12/23 biological agents.
Summary
Background Dermoscopy is useful in evaluating skin tumours, but its applicability extends also to the field of inflammatory skin disorders. Plaque psoriasis (PP), dermatitis, lichen planus ...(LP) and pityriasis rosea (PR) are common inflammatory skin diseases, but little is currently known about their dermoscopic features.
Objectives To determine and compare the dermoscopic patterns associated with PP, dermatitis, LP and PR and to assess the validity of certain dermoscopic criteria in the diagnosis of PP.
Methods Patients with PP, dermatitis, LP and PR were prospectively enrolled. The single most recently developed lesion was examined dermoscopically and histopathologically. Variables included vascular morphology, vascular arrangement, background colour, scale colour, scale distribution and presence of Wickham striae. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot receiver‐operator characteristic curves.
Results Eighty‐three patients with PP and 86 patients with either dermatitis, LP or PR were included in the study. Dotted vessels in a regular arrangement over a light red background and white scales were highly predictive for the diagnosis of PP, whereas dermatitis more commonly showed yellow scales and dotted vessels in a patchy arrangement. PR was characterized by yellowish background, dotted vessels and peripheral scales; whitish lines (Wickham striae) were seen exclusively in LP.
Conclusions PP, LP, PR and dermatitis show specific dermoscopic patterns that may aid their clinical diagnosis. Certain combinations of dermoscopic features can reliably predict the diagnosis of PP.
Summary
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.
What's already known about this topic?
Ex vivo fluorescent confocal microscopy (FCM) is a new imaging tool that offers an attractive alternative to conventional frozen histology for the detection of margins in freshly excised tissue.
What does this study add?
Our study of 753 specimens found that FCM is a valid imaging tool to assess basal cell carcinoma margins in Mohs surgery, with high diagnostic accuracy when compared with frozen sections.
Furthermore, FCM is a safe procedure that result in few false‐negative cases when compared with permanent formalin‐embedded sections.
Linked Comment: Notingher. Br J Dermatol 2019; 180:1295–1296.
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Summary
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.
What's already known about this topic?
Spitzoid lesions represent a challenging and controversial group of tumours, in terms of clinical recognition, biological behaviour and management strategies.
Dermoscopy improves the clinical recognition of Spitz naevi, but a morphological overlap between Spitz naevi and spitzoid melanoma does exist.
Histopathologically, some tumours cannot be safely diagnosed either as Spitz naevi or as melanomas.
These controversies result in a significant inconsistency of management of spitzoid tumours among clinicians.
What does this study add?
Three dermoscopic patterns may be considered as suggestive of a Spitz naevus: starburst pattern, regularly distributed dotted vessels and globular pattern with reticular depigmentation.
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 the age, to rule out atypical Spitz tumours.
Dermoscopically symmetric flat spitzoid lesions should be managed according to the age of the patient.
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Summary
Background
Little is known about the variability of the dermoscopic criteria of squamous cell carcinoma (SCC) according to the histopathological differentiation grade.
Objectives
To evaluate ...whether specific dermoscopic criteria can predict the diagnosis of poorly differentiated SCC compared with well‐ and moderately differentiated SCC.
Methods
Clinical and dermoscopic images of SCCs were retrospectively evaluated for the presence of predefined criteria. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot receiver–operator characteristic curves.
Results
Of 143 SCCs included, 48 (33·5%) were well differentiated, 45 (31·5%) were moderately differentiated and 50 (35·0%) were poorly differentiated. Flat tumours had a fourfold increased probability of being poorly differentiated. Dermoscopically, the presence of a predominantly red colour posed a 13‐fold possibility of poor differentiation, whereas a predominantly white and white–yellow colour decreased the odds of poorly differentiated SCC by 97% each. The presence of vessels in more than 50% of the tumour's surface, a diffuse distribution of vessels and bleeding were significantly associated with poor differentiation, while scale/keratin was a potent predictor of well‐ or moderately differentiated tumours.
Conclusions
Dermoscopy may be regarded as a reliable preoperative tool to distinguish poorly from well‐ and moderately differentiated SCC. Given that poor differentiation of SCC represents an independent risk factor for recurrence, metastasis and disease‐specific death, identifying poorly differentiated tumours in vivo may enhance their appropriate management.
What's already known about this topic?
While the dermoscopic criteria of squamous cell carcinoma (SCC) have been well described, little is currently known about the variability of these criteria with respect to the histopathological grade of differentiation in SCC.
What does this study add?
Poorly differentiated SCC is dermoscopically typified by a predominantly red colour, attributed to the presence of bleeding and/or dense vascularity.
Identifying poorly differentiated tumours in vivo may enhance their appropriate management.
Summary
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.
What's already known about this topic?
Approximately one‐third of acral melanomas (AMs) lack a dermoscopic parallel ridge pattern, rendering their detection more troublesome.
What does this study add?
A scoring system composed of six variables achieves the highest diagnostic accuracy for AM.
Application of this diagnostic scheme minimizes the possibility of missing AMs that are not dermoscopically characterized by a parallel ridge pattern.
Linked Comment: Rao and Giambrone, Br J Dermatol 2015; 173: 893–894.
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.
Summary
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.
What's already known about this topic?
Data on reflectance confocal microscopy (RCM) diagnostic features for in situ melanoma are still lacking.
What does this study add?
Findings of an atypical network and regression from dermoscopy, and epidermal pagetoid spreading and junctional cytological atypia from RCM are positive predictors for in situ melanoma diagnosis.
This multistep algorithm can be used routinely in tertiary centres to improve the accuracy of diagnosing in situ melanoma.
Linked Comment: Bahadoran. Br J Dermatol 2018; 179:12–13.
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