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Abstract: Rhinophyma is the advanced stage of rosacea and manifests clinically with disfigurement of the nose. The histopathology has been classified into classical and severe types. We studied the clinicopathological characteristics of 8 cases with the diagnosis of rhinophyma. In 5 of 9 specimens, floret-like multinucleated giant cells containing lipid were identified. This finding, to the best of our knowledge, has not been previously described., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Conflicts of interest The authors declare they have no conflicts of interest.

Lentigo Maligna is a benign subtype of melanoma in situ and can progress to lentigo maligna melanoma, which is invasive. Complete surgical excision is the gold standard of treatment but requires large margins. If affecting the peri-ocular region, surgical excision leads to extensive defects, complex reconstructions, and functional impairment of the protection of the ocular surface. Here we review the reported literature about the use of Imiquimod 5% topical cream for lentigo maligna of the eyelid, the treatment outcomes, side effects and tolerance. In addition, the side effects of imiquimod treatment of non-LM lesions are described to help better inform the decision-making process. Treatment for peri-ocular Lentigo maligna showed a 56-86% complete treatment response and a 90% tolerability rate. However, reported treatment protocols vary and histopathological confirmation of clearance was only obtained in 56%. Further studies are required to determine the optimal treatment protocol to maximise clearance rates. Overall, Imiquimod was well tolerated in the peri-ocular area., (© 2022. Crown.)

Optical coherence tomography (OCT) is a noninvasive optical imaging method that can generate high-resolution en face and cross-sectional images of the skin in vivo to a maximum depth of 2 mm. While OCT holds considerable potential for noninvasive diagnosis and disease monitoring, it is poorly understood by many dermatologists. Here we aim to equip the practising dermatologist with an understanding of the principles of skin OCT and the potential clinical indications. We begin with an introduction to the technology and discuss the different modalities of OCT including angiographic (dynamic) OCT, which can image cutaneous blood vessels at high resolution. Next we review clinical applications. OCT has been most extensively investigated in the diagnosis of keratinocyte carcinomas, particularly basal cell carcinoma. To date, OCT has not proven sufficiently accurate for the robust diagnosis of malignant melanoma; however, the evaluation of abnormal vasculature with angiographic OCT is an area of active investigation. OCT, and in particular angiographic OCT, also shows promise in monitoring the response to therapy of inflammatory dermatoses, such as psoriasis and connective tissues disease. We additionally discuss a potential role for artificial intelligence in improving the accuracy of interpretation of OCT imaging data., (© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Early accurate detection of all skin cancer types is important to guide appropriate management and improve morbidity and survival. Basal cell carcinoma (BCC) is usually a localised skin cancer but with potential to infiltrate and damage surrounding tissue, whereas cutaneous squamous cell carcinoma (cSCC) and melanoma are higher risk skin cancers with the potential to metastasise and ultimately lead to death. When used in conjunction with clinical or dermoscopic suspicion of malignancy, or both, reflectance confocal microscopy (RCM) may help to identify cancers eligible for non-surgical treatment without the need for a diagnostic biopsy, particularly in people with suspected BCC. Any potential benefit must be balanced against the risk of any misdiagnoses., Objectives: To determine the diagnostic accuracy of RCM for the detection of BCC, cSCC, or any skin cancer in adults with any suspicious lesion and lesions that are difficult to diagnose (equivocal); and to compare its accuracy with that of usual practice (visual inspection or dermoscopy, or both)., Search Methods: We undertook a comprehensive search of the following databases from inception to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL; CPCI; Zetoc; Science Citation Index; US National Institutes of Health Ongoing Trials Register; NIHR Clinical Research Network Portfolio Database; and the World Health Organization International Clinical Trials Registry Platform. We studied reference lists and published systematic review articles., Selection Criteria: Studies of any design that evaluated the accuracy of RCM alone, or RCM in comparison to visual inspection or dermoscopy, or both, in adults with lesions suspicious for skin cancer compared with a reference standard of either histological confirmation or clinical follow-up, or both., Data Collection and Analysis: Two review authors independently extracted data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated summary sensitivities and specificities using the bivariate hierarchical model. For computation of likely numbers of true-positive, false-positive, false-negative, and true-negative findings in the 'Summary of findings' tables, we applied summary sensitivity and specificity estimates to lower quartile, median and upper quartiles of the prevalence observed in the study groups. We also investigated the impact of observer experience., Main Results: The review included 10 studies reporting on 11 study cohorts. All 11 cohorts reported data for the detection of BCC, including 2037 lesions (464 with BCC); and four cohorts reported data for the detection of cSCC, including 834 lesions (71 with cSCC). Only one study also reported data for the detection of BCC or cSCC using dermoscopy, limiting comparisons between RCM and dermoscopy. Studies were at high or unclear risk of bias across almost all methodological quality domains, and were of high or unclear concern regarding applicability of the evidence. Selective participant recruitment, unclear blinding of the reference test, and exclusions due to image quality or technical difficulties were observed. It was unclear whether studies were representative of populations eligible for testing with RCM, and test interpretation was often undertaken using images, remotely from the participant and the interpreter blinded to clinical information that would normally be available in practice.Meta-analysis found RCM to be more sensitive but less specific for the detection of BCC in studies of participants with equivocal lesions (sensitivity 94%, 95% confidence interval (CI) 79% to 98%; specificity 85%, 95% CI 72% to 92%; 3 studies) compared to studies that included any suspicious lesion (sensitivity 76%, 95% CI 45% to 92%; specificity 95%, 95% CI 66% to 99%; 4 studies), although CIs were wide. At the median prevalence of disease of 12.5% observed in studies including any suspicious lesion, applying these results to a hypothetical population of 1000 lesions results in 30 BCCs missed with 44 false-positive results (lesions misdiagnosed as BCCs). At the median prevalence of disease of 15% observed in studies of equivocal lesions, nine BCCs would be missed with 128 false-positive results in a population of 1000 lesions. Across both sets of studies, up to 15% of these false-positive lesions were observed to be melanomas mistaken for BCCs. There was some suggestion of higher sensitivities in studies with more experienced observers. Summary sensitivity and specificity could not be estimated for the detection of cSCC due to paucity of data., Authors' Conclusions: There is insufficient evidence for the use of RCM for the diagnosis of BCC or cSCC in either population group. A possible role for RCM in clinical practice is as a tool to avoid diagnostic biopsies in lesions with a relatively high clinical suspicion of BCC. The potential for, and consequences of, misclassification of other skin cancers such as melanoma as BCCs requires further research. Importantly, data are lacking that compare RCM to standard clinical practice (with or without dermoscopy).

Background: Melanoma has one of the fastest rising incidence rates of any cancer. It accounts for a small percentage of skin cancer cases but is responsible for the majority of skin cancer deaths. Early detection and treatment is key to improving survival; however, anxiety around missing early cases needs to be balanced against appropriate levels of referral and excision of benign lesions. Used in conjunction with clinical or dermoscopic suspicion of malignancy, or both, reflectance confocal microscopy (RCM) may reduce unnecessary excisions without missing melanoma cases., Objectives: To determine the diagnostic accuracy of reflectance confocal microscopy for the detection of cutaneous invasive melanoma and atypical intraepidermal melanocytic variants in adults with any lesion suspicious for melanoma and lesions that are difficult to diagnose, and to compare its accuracy with that of dermoscopy., Search Methods: We undertook a comprehensive search of the following databases from inception up to August 2016: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; and seven other databases. We studied reference lists and published systematic review articles., Selection Criteria: Studies of any design that evaluated RCM alone, or RCM in comparison to dermoscopy, in adults with lesions suspicious for melanoma or atypical intraepidermal melanocytic variants, compared with a reference standard of either histological confirmation or clinical follow-up., Data Collection and Analysis: Two review authors independently extracted all data using a standardised data extraction and quality assessment form (based on QUADAS-2). We contacted authors of included studies where information related to the target condition or diagnostic threshold were missing. We estimated summary sensitivities and specificities per algorithm and threshold using the bivariate hierarchical model. To compare RCM with dermoscopy, we grouped studies by population (defined by difficulty of lesion diagnosis) and combined data using hierarchical summary receiver operating characteristic (SROC) methods. Analysis of studies allowing direct comparison between tests was undertaken. To facilitate interpretation of results, we computed values of specificity at the point on the SROC curve with 90% sensitivity as this value lies within the estimates for the majority of analyses. We investigated the impact of using a purposely developed RCM algorithm and in-person test interpretation., Main Results: The search identified 18 publications reporting on 19 study cohorts with 2838 lesions (including 658 with melanoma), which provided 67 datasets for RCM and seven for dermoscopy. Studies were generally at high or unclear risk of bias across almost all domains and of high or unclear concern regarding applicability of the evidence. Selective participant recruitment, lack of blinding of the reference test to the RCM result, and differential verification were particularly problematic. Studies may not be representative of populations eligible for RCM, and test interpretation was often undertaken remotely from the patient and blinded to clinical information.Meta-analysis found RCM to be more accurate than dermoscopy in studies of participants with any lesion suspicious for melanoma and in participants with lesions that were more difficult to diagnose (equivocal lesion populations). Assuming a fixed sensitivity of 90% for both tests, specificities were 82% for RCM and 42% for dermoscopy for any lesion suspicious for melanoma (9 RCM datasets; 1452 lesions and 370 melanomas). For a hypothetical population of 1000 lesions at the median observed melanoma prevalence of 30%, this equated to a reduction in unnecessary excisions with RCM of 280 compared to dermoscopy, with 30 melanomas missed by both tests. For studies in equivocal lesions, specificities of 86% would be observed for RCM and 49% for dermoscopy (7 RCM datasets; 1177 lesions and 180 melanomas). At the median observed melanoma prevalence of 20%, this reduced unnecessary excisions by 296 with RCM compared with dermoscopy, with 20 melanomas missed by both tests. Across all populations, algorithms and thresholds assessed, the sensitivity and specificity of the Pellacani RCM score at a threshold of three or greater were estimated at 92% (95% confidence interval (CI) 87 to 95) for RCM and 72% (95% CI 62 to 81) for dermoscopy., Authors' Conclusions: RCM may have a potential role in clinical practice, particularly for the assessment of lesions that are difficult to diagnose using visual inspection and dermoscopy alone, where the evidence suggests that RCM may be both more sensitive and specific in comparison to dermoscopy. Given the paucity of data to allow comparison with dermoscopy, the results presented require further confirmation in prospective studies comparing RCM with dermoscopy in a real-world setting in a representative population.

Background: In the United Kingdom, 350,000 patients per year are referred to hospital clinics with suspicious moles, and approximately half undergo a biopsy to identify the 5%-10% who require further treatment. If cancer cannot be ruled out clinically and on the basis of biopsy results, the lesion is surgically removed. One type of precancerous mole, called lentigo maligna, is particularly challenging to delineate and treat. Reflectance confocal microscopy (VivaScope, Caliber Imaging & Diagnostics) is an imaging technique that can supplement dermoscopy in identifying whether a clinically suspicious mole is malignant and can better assess lentigo maligna margins for excision. It allows clinicians to visualize the skin lesion to a depth of 200 microns with subcellular resolution, described as quasi-histological, and therefore better guide more accurate diagnoses., Objective: The aim of this paper is to describe a prospective, single blinded, multicenter study to examine patients with clinically suspicious moles or lentigo maligna to determine whether confocal microscopy can both reduce the number of unnecessary biopsies of moles and more accurately guide the surgical excision margins of lentigo maligna., Methods: This study will prospectively recruit adults into the following two cohorts: diagnostic accuracy and margin delineation. The diagnostic accuracy cohort will assess people with clinically suspicious lesions suspected of being diagnosed with melanoma and having an equivocal finding on dermoscopy or persistent clinical suspicion despite normal dermoscopy. Diagnostic accuracy will include the sensitivity and specificity of VivaScope in comparison with the histological diagnosis as the gold standard for patients. The margin delineation cohort will assess the ability of VivaScope to accurately delineate the margins of lentigo maligna compared with that of dermoscopy alone using margins taken during Mohs micrographic surgery as the gold standard. The primary study outcomes will be the diagnostic accuracy of VivaScope for the first cohort of patients and margin agreement between VivaScope and the final pathology report for the second cohort of patients., Results: Funding for this proposed research is being secured., Conclusions: The outcomes of the proposed study will indicate how many biopsies of nonmelanoma lesions, which are potentially unnecessary, could be prevented. This would reduce patient anxiety and cost to the National Health Service (NHS) in the United Kingdom. Improved margin delineation of lentigo maligna could also improve the surgical clearance rates and decrease overall cost. The results would demonstrate whether the adoption of VivaScope would potentially benefit patients and the NHS., Registered Report Identifier: RR1-10.2196/9296., (©Naomi D. Herz, Anastasia Chalkidou, Fiona Reid, Stephen F. Keevil, Andrew Coleman, Emma Craythorne, Rakesh Patalay. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 09.08.2018.)

For squamous cell carcinoma (SCC) treated using Mohs micrographic surgery (MMS), interpretation of haematoxylin and eosin-stained frozen sections can be challenging. In these situations, ancillary use of immunostaining is a useful tool for the Mohs surgeon. However, use of immunostaining in MMS laboratories is limited, mainly because current manual immunostaining platforms are subject to operator error, and automated immunostaining, albeit accurate, is too slow for inclusion in MMS. In this report, we describe a novel 1-hour protocol for rapid frozen section immunocytochemistry, using the pancytokeratin markers AE1/AE3. This protocol has been specifically designed to integrate the speed of manual techniques and the accuracy of automated platforms, making it a valuable addition to the MMS laboratory. We propose that in selected or histologically challenging cases, there is a role for the use of this novel protocol, allowing the Mohs surgeon to more confidently declare tumour clearance, thus preventing further unnecessary surgery and preserving healthy tissue., (© 2018 British Association of Dermatologists.)

Background: Skin cancer is one of the most common cancers in the UK. Patients with suspicious skin lesions are assessed clinically with/without dermoscopy, and lesions still considered suspicious are then surgically removed or have the diagnosis confirmed by a punch biopsy., Aim: To evaluate the diagnostic accuracy of the in vivo VivaScope © reflective confocal microscopy (RCM) system, a noninvasive technology designed to provide a more accurate presurgical diagnosis, leading to fewer biopsies of benign lesions, or to provide greater accuracy for lesion margins., Methods: MEDLINE, EMBASE and the Cochrane Library were searched to identify studies evaluating dermoscopy plus RCM, or RCM alone, with histopathology as the reference test. Clinical experts were also contacted for information on unpublished studies., Results: Eleven studies met the inclusion criteria but were too heterogeneous to be combined by meta-analysis. Results indicated that VivaScope subsequent to dermoscopy may improve diagnostic accuracy of malignant melanomas compared with dermoscopy. For margin delineation, the data suggest that mapping using VivaScope 1500 for lentigo maligna (LM) and LM melanoma may improve accuracy in terms of complete excision of lesions compared with dermoscopically determined margins. For basal cell carcinoma, the limited data show high diagnostic accuracy with both VivaScope 1500 and VivaScope 3000. Evidence on the effectiveness of VivaScope in diagnosing cutaneous squamous cell carcinomas was very limited., Conclusion: The use of VivaScope 1500 following dermoscopy may improve patient care and management of suspicious skin lesions, although the generalizability of these results to the UK population remains unclear., (© 2017 British Association of Dermatologists.)

Wells syndrome is a rare disorder of unknown etiology. Precipitants include insect bites, infections, medications, malignancies, and vaccinations. Possible mechanisms include hypersensitivity reactions to antigens. There are four reports in the literature of Wells syndrome precipitated by vaccinations (hepatitis B vaccine, tetanus vaccine, tetanus-diptheria vaccine and triple antigen vaccine). We present a further case of Wells syndrome in a 22-month-old child after influenza vaccine as a novel trigger not previously reported., (© 2015 Wiley Periodicals, Inc.)

We present the first detailed study using multispectral multiphoton fluorescence lifetime imaging to differentiate basal cell carcinoma cells (BCCs) from normal keratinocytes. Images were acquired from 19 freshly excised BCCs and 27 samples of normal skin (in & ex vivo). Features from fluorescence lifetime images were used to discriminate BCCs with a sensitivity/specificity of 79%/93% respectively. A mosaic of BCC fluorescence lifetime images covering >1 mm(2) is also presented, demonstrating the potential for tumour margin delineation. Using 10,462 manually segmented cells from the image data, we quantify the cellular morphology and spectroscopic differences between BCCs and normal skin for the first time. Statistically significant increases were found in the fluorescence lifetimes of cells from BCCs in all spectral channels, ranging from 19.9% (425-515 nm spectral emission) to 39.8% (620-655 nm emission). A discriminant analysis based diagnostic algorithm allowed the fraction of cells classified as malignant to be calculated for each patient. This yielded a receiver operator characteristic area under the curve for the detection of BCC of 0.83. We have used both morphological and spectroscopic parameters to discriminate BCC from normal skin, and provide a comprehensive base for how this technique could be used for BCC assessment in clinical practice.

We explore the diagnostic potential of imaging endogenous fluorophores using two photon microscopy and fluorescence lifetime imaging (FLIM) in human skin with two spectral detection channels. Freshly excised benign dysplastic nevi (DN) and malignant nodular Basal Cell Carcinomas (nBCCs) were excited at 760 nm. The resulting fluorescence signal was binned manually on a cell by cell basis. This improved the reliability of fitting using a double exponential decay model and allowed the fluorescence signatures from different cell populations within the tissue to be identified and studied. We also performed a direct comparison between different diagnostic groups. A statistically significant difference between the median mean fluorescence lifetime of 2.79 ns versus 2.52 ns (blue channel, 300-500 nm) and 2.08 ns versus 1.33 ns (green channel, 500-640 nm) was found between nBCCs and DN respectively, using the Mann-Whitney U test (p < 0.01). Further differences in the distribution of fluorescence lifetime parameters and inter-patient variability are also discussed.

When performing multiphoton fluorescence lifetime imaging in multiple spectral emission channels, an instrument response function must be acquired in each channel if accurate measurements of complex fluorescence decays are to be performed. Although this can be achieved using the reference reconvolution technique, it is difficult to identify suitable fluorophores with a mono-exponential fluorescence decay across a broad emission spectrum. We present a solution to this problem by measuring the IRF using the ultrafast luminescence from gold nanorods. We show that ultrafast gold nanorod luminescence allows the IRF to be directly obtained in multiple spectral channels simultaneously across a wide spectral range. We validate this approach by presenting an analysis of multispectral autofluorescence FLIM data obtained from human skin ex vivo.