Gabriela Lladó Grove, Kevin Jacobsen, Nina Loeth Maartensson, Merete Haedersdal
{"title":"Subclinical effects of botulinum toxin A and microwave thermolysis for axillary hyperhidrosis: A descriptive study with line-field confocal optical coherence tomography and histology","authors":"Gabriela Lladó Grove, Kevin Jacobsen, Nina Loeth Maartensson, Merete Haedersdal","doi":"10.1111/exd.15110","DOIUrl":"10.1111/exd.15110","url":null,"abstract":"<p>Botulinum toxin A (BTX) and microwave thermolysis (MWT) are standard axillary hyperhidrosis treatments, but comparison of their subclinical effects is lacking. Line-field confocal optical coherence tomography (LC-OCT) is a promising non-invasive imaging tool for visualizing tissue-interactions. This study aimed to describe subclinical effects of BTX and MWT for axillary hyperhidrosis with LC-OCT-imaging compared to histology. This study derived from an intra-individual, randomized, controlled trial, treating axillary hyperhidrosis with BTX versus MWT. Subclinical effects based on LC-OCT images from baseline and 6-month follow-up (<i>n</i> = 8 patients) were evaluated and compared to corresponding histological samples. At baseline, LC-OCT visualized eccrine pores at the skin surface and ducts in the upper dermis (500 μm), but not deeper-lying sweat glands. Histology identified entire sweat glands. Six months post-treatment, LC-OCT revealed no detectable morphology changes in any BTX-treated axillae (100%), while recognizing obstructed eccrine pores and atrophy of eccrine ducts in most MWT-treated axillae (75%). Histology corroborated LC-OCT findings, while also showing substantial changes to entire sweat glands. LC-OCT enabled visualization of subclinical alterations of superficial eccrine ducts after MWT and unchanged morphology after BTX. LC-OCT is a promising tool for non-invasive assessment of treatment-specific tissue-interactions that can be complementary to histology.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hiroshi Maeno, Yoko Suzuki-Horiuchi, Ayaka Funakoshi, Onuma Chumsakul, Yasunari Sato, Tsuyoshi Ishii, John T. Seykora
{"title":"miR-4521—A novel biomarker for human lentigos","authors":"Hiroshi Maeno, Yoko Suzuki-Horiuchi, Ayaka Funakoshi, Onuma Chumsakul, Yasunari Sato, Tsuyoshi Ishii, John T. Seykora","doi":"10.1111/exd.15118","DOIUrl":"10.1111/exd.15118","url":null,"abstract":"<p>Lentigos are hyperpigmented skin lesions that can vary in size and shape, typically appearing on the face, hands and shoulders, usually on sun exposed skin. Currently, the molecular pathogenesis of lentigos remains unclear. As a first step in identifying potential biomarkers of lentigos that may drive lentigo formation, we performed laser-capture microdissection (LCM) on the lesional epidermis of lentigos from five archived patient samples and, as a control, from the epidermis of three unremarkable skin samples matching for site, sex and age (Table S1). Total RNA was extracted from the micro-dissected lentigo and control tissue samples to perform transcriptomic microarray analysis (ThermoFisher Human transcriptome Array 2.0.) to identify potential biomarkers of lentigos. Bioinformatics analysis of data obtained from the whole transcriptome array (ThermoFisher TAC4.0 software package, Figure S1) identified coding and non-coding transcripts that were significantly differentially expressed in lentigos; some of these differentially expressed transcripts are associated with melanogenesis which is consistent with previous studies (Table S2).<span><sup>1, 2</sup></span> Multiple non-coding RNAs were found to be differentially regulated in the top 10 differentially expressed genes, including small nucleolar RNA species (snoRNA) and micro-RNA species (miR) (Tables S2 and S3). Studies have shown evidence that microRNAs play important biological roles ranging from development, differentiation, tumour progression or suppression.<span><sup>3</sup></span> In our data, one of the most highly expressed microRNAs was miR-4521, which is recently reported to act as a “tumor suppressor miR” to decrease the expression of pro-oncogenic targets such as forkhead box protein M1 and insulin-like growth factor 2.<span><sup>4</sup></span> Therefore, we further characterized the expression pattern of has-miR-4521 to validate it as a biomarker of lentigo.</p><p>The expression of miR-4521 in lentigos was evaluated by qRT-PCR and miR RNA in situ hybridization. miR-4521 expression level was 3.61 higher than that of control epidermis by qRT-PCR (Figure 1A, Mann–Whitney test, lentigo <i>n</i> = 6, control <i>n</i> = 4, <i>p</i> < 0.05). miR-4521 RNA in situ hybridization assays demonstrated stronger positive signals for the miR-4521 anti-sense probe in the epidermis between the stratum basalis and the stratum granulosum (Figure 1 E,G and H) compared to matched control skin (Figure 1D,F). In addition, the signal intensity of the anti-sense probe in the lentigo epidermis (Figure 1H) was higher than that of adjacent un-remarkable epidermis (Figure 1G) and matched control (Figure 1F). Together, these data indicate that miR-4521 expression is increased in lentigos primarily in the lesional keratinocytes. Melanocyte numbers were determined in all samples and there was no statistically significant difference noted (lentigo; 2.74 ± 0.37 SE /0.1 mm, control; 3.71 ± 0.21 SE / 0.1 mm, ","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Malassezia specific IgE in head and neck dermatitis of eczema: A systematic review & meta-analysis","authors":"Hui Xin See Tow, Yik Weng Yew","doi":"10.1111/exd.15108","DOIUrl":"10.1111/exd.15108","url":null,"abstract":"<p>Head and neck atopic dermatitis (HNAD) is a subtype of atopic dermatitis (AD), a common inflammatory skin condition with a distinctive clinical appearance. <i>Malassezia</i> spp., a predominant skin yeast, is considered to exacerbate HNAD. In this study, we investigate the prevalence of <i>Malassezia</i>-specific IgE among HNAD patients. A comprehensive search was performed for observational studies analysing the association between <i>Malassezia</i>-specific IgE and HNAD. This study was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 checklist and quality was assessed via the Newcastle-Ottawa Quality Assessment Scale (NOS). Fourteen observational studies (840 patients) were included in the analysis. 58% of HNAD patients were male (95% CI: 45.2–69.7). Overall prevalence of <i>Malassezia</i>-specific IgE among HNAD patients was 79.3% (95% CI: 57.5–91.5). Prevalence of <i>Malassezia-</i>specific IgE among HNAD patients varied significantly between geographical regions (<i>p</i> = 0.0441), with 88% in non-Asian regions (95% CI: 61.06–97.17) and 54.73% in Asian regions (95% CI: 34.36–73.63). <i>Malassezia</i>-specific IgE prevalence among HNAD patients varied significantly among studies of higher and lower NOS quality score (<i>p</i> = 0.0386), with 95.42% in studies with NOS ≥7 (95% CI: 63.54–99.60) and 58.05% in studies with NOS <7 (95% CI: 41.44–73.01). <i>Malassezia</i>-specific IgE prevalence among HNAD patients did not vary significantly between more and less predominant <i>Malassezia</i> species (<i>p</i> = 0.1048). <i>Malassezia</i> spp. plays a crucial role in the pathogenesis of HNAD, and IgE anti-<i>Malassezia</i> antibodies appeared to be a common marker for HNAD. Understanding the pathophysiology of <i>Malassezia</i> in HNAD can help develop more targeted therapeutic approaches in managing AD.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Mias, A. Stennevin, G. Doat, A. Catté, J. Chlasta, S. Bessou-Touya, H. Duplan
{"title":"Effect of a low-mineralized thermal spring water on skin barrier mechanical properties using atomic force microscopy","authors":"C. Mias, A. Stennevin, G. Doat, A. Catté, J. Chlasta, S. Bessou-Touya, H. Duplan","doi":"10.1111/exd.15113","DOIUrl":"10.1111/exd.15113","url":null,"abstract":"<p>The mineral content of thermal spring water (TSW) applied to the skin surface can directly influence the skin barrier. Indeed, our previous study showed that Avène TSW (ATSW), a low mineral content thermal spring water, protects the stratum corneum from dehydration compared to a mineral-rich TSW (MR-TSW) and maintains skin surface ultrastructure. While many TSWs have been recognized to have beneficial effects on skin, little is known about their localized and specific effects on skin barrier biomechanics at the nanometric scale. The aim of this study was to compare the effects of ATSW with a reference, MR-TSW, on the biomechanical barrier properties of the skin under homeostasis conditions using atomic force microscopy (AFM). AFM was used to obtain a precise nanomechanical mapping of the skin surface after three applications of both TSW. This provides specific information on the skin topographical profile and elasticity. The topographic profile of skin samples showed a specific compaction of the skin layers after application of MR-TSW, characterized by an increase of the total number of external skin layers, compared to non-treated samples. By contrast, ATSW did not modify the skin topographic profile. High-resolution force/volume acquisitions to capture the elastic modulus showed that it was directly correlated with skin rigidity. The elastic modulus strongly and significantly increased after MR-TSW application compared to non-treated skin. By contrast, applications of ATSW did not increase elastic modulus. These data demonstrate that applications of MR-TSW significantly modified skin barrier properties by increasing skin surface layer compaction and skin rigidity. By contrast, ATSW did not modify the topographical profile of skin explants nor induce mechanical stress at the level of the stratum corneum, indicating it does not disrupt the biophysical properties linked to skin surface integrity.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"IL-4 and IL-13 are not involved in IL-31-induced itch-associated scratching behaviour in mice","authors":"Rana Kawai, Nao Ichimasu, Kazumoto Katagiri","doi":"10.1111/exd.15115","DOIUrl":"10.1111/exd.15115","url":null,"abstract":"<p>Itchy skin or pruritus is a common cutaneous symptom that causes an urge to scratch, and the role of interleukins (IL) in itchy skin has been widely studied. IL-4 and IL-13 are known to induce chronic itch. Similarly, the direct role of IL-31 in inducing itch has been demonstrated in clinical situations such as atopic dermatitis and prurigo nodularis. Moreover, IL-4 receptor α antibodies (dupilumab) and IL-31 receptor A antibodies (nemolizumab) inhibit pruritus. However, the interplay between these ILs in pruritus remains unclear. Therefore, we investigated the reciprocal effects of these cytokines on pruritus in mice. The intradermal administration of IL-31 induced itch-associated scratching behaviour in a dose-dependent manner. Interestingly, the amount of IL-31 and IL-4/IL-13, co-administration or 30 min pre-administration of IL-4/IL-13 and intradermal or intravenous pre-administration of IL-4 did not affect IL-31-induced itch-associated scratching behaviour when it was observed for 30 min, 2 h, 24 h or 48 h. Pre-administration of neutralising antibodies against IL-4 and IL-13 also did not affect IL-31-induced itch-associated scratching behaviour. These results suggest that IL-31 can induce itching independently of IL-4 and IL-13 in vivo.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Research progress on the mechanism and signalling pathway of ferroptosis and its potential role in dermatosis research","authors":"Min Li, Jian Gong, Qiao Liu, Weiwei Wu","doi":"10.1111/exd.15114","DOIUrl":"10.1111/exd.15114","url":null,"abstract":"<p>Ferroptosis is a novel type of cell death that is dependent on lipid peroxidation and iron accumulation, which distinguishes it from other types of programmed cell death. Current research indicates a significant association between ferroptosis and various pathological conditions, including cancer, neurological disorders, and cardiovascular diseases, albeit with a relatively unexplored role in dermatological afflictions. This paper elaborates on the mechanisms and signalling pathways of ferroptosis, summarizing the recent studies on ferroptosis and its related factors in dermatosis. Our objective is to shed light on novel perspectives and therapeutic strategies for dermatosis, enhancing the understanding of this under-researched area through this comprehensive review.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yun Liu, Teng-Xiao Ma, Peng-Fei Fan, Ze Wang, Zhe Wang, Lei Li
{"title":"STAT3-induced lncRNA GNAS-AS1 accelerates keloid formation by mediating the miR-196a-5p/CXCL12/STAT3 axis in a feedback loop","authors":"Yun Liu, Teng-Xiao Ma, Peng-Fei Fan, Ze Wang, Zhe Wang, Lei Li","doi":"10.1111/exd.15111","DOIUrl":"10.1111/exd.15111","url":null,"abstract":"<p>Keloids are pathological scar tissue resulting from skin trauma or spontaneous formation, often accompanied by itching and pain. Although GNAS antisense RNA 1 (GNAS-AS1) shows abnormal upregulation in keloids, the underlying molecular mechanism is unclear. The levels of genes and proteins in clinical tissues from patients with keloids and human keloid fibroblasts (HKFs) were measured using quantitative reverse transcription PCR, western blot and enzyme-linked immunosorbent assay. The features of HKFs, including proliferation and migration, were evaluated using cell counting kit 8 and a wound healing assay. The colocalization of GNAS-AS1 and miR-196a-5p in HKFs was measured using fluorescence in situ hybridization. The relationships among GNAS-AS1, miR-196a-5p and C-X-C motif chemokine ligand 12 (CXCL12) in samples from patients with keloids were analysed by Pearson correlation analysis. Gene interactions were validated by chromatin immunoprecipitation and luciferase reporter assays. GNAS-AS1 and CXCL12 expression were upregulated and miR-196a-5p expression was downregulated in clinical tissues from patients with keloids. GNAS-AS1 knockdown inhibited proliferation, migration, and extracellular matrix (ECM) accumulation of HKFs, all of which were reversed by miR-196a-5p downregulation. Signal transducer and activator of transcription 3 (STAT3) induced GNAS-AS1 transcription through GNAS-AS1 promoter interaction, and niclosamide, a STAT3 inhibitor, decreased GNAS-AS1 expression. GNAS-AS1 positively regulated CXCL12 by sponging miR-196-5p. Furthermore, CXCL12 knockdown restrained STAT3 phosphorylation in HKFs. Our findings revealed a feedback loop of STAT3/GNAS-AS1/miR-196a-5p/CXCL12/STAT3 that promoted HKF proliferation, migration and ECM accumulation and affected keloid progression.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nuclear receptors for epidermal lipid barrier: Advances in mechanisms and applications","authors":"Xidie Yin, Yu Yan, Jiandan Li, Zhi Cao, Shuzhan Shen, Qihang Chang, Yiting Zhao, Xiuli Wang, Peiru Wang","doi":"10.1111/exd.15107","DOIUrl":"10.1111/exd.15107","url":null,"abstract":"<p>The skin plays an essential role in preventing the entry of external environmental threats and the loss of internal substances, depending on the epidermal permeability barrier. Nuclear receptors (NRs), present in various tissues and organs including full-thickness skin, have been demonstrated to exert significant effects on the epidermal lipid barrier. Formation of the lipid lamellar membrane and the normal proliferation and differentiation of keratinocytes (KCs) are crucial for the development of the epidermal permeability barrier and is regulated by specific NRs such as PPAR, LXR, VDR, RAR/RXR, AHR, PXR and FXR. These receptors play a key role in regulating KC differentiation and the entire process of epidermal lipid synthesis, processing and secretion. Lipids derived from sebaceous glands are influenced by NRs as well and participate in regulation of the epidermal lipid barrier. Furthermore, intricate interplay exists between these receptors. Disturbance of barrier function leads to a range of diseases, including psoriasis, atopic dermatitis and acne. Targeting these NRs with agonists or antagonists modulate pathways involved in lipid synthesis and cell differentiation, suggesting potential therapeutic approaches for dermatosis associated with barrier damage. This review focuses on the regulatory role of NRs in the maintenance and processing of the epidermal lipid barrier through their effects on skin lipid synthesis and KC differentiation, providing novel insights for drug targets to facilitate precision medicine strategies.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carl Kellett, Ranjit K. Bhogal, Natalia V. Botchkareva, Michael Y. Fessing
{"title":"ATP-dependent chromatin remodeller brahma related gene 1 promotes keratinocyte migration and modulates cell Signalling during wound healing in human skin","authors":"Carl Kellett, Ranjit K. Bhogal, Natalia V. Botchkareva, Michael Y. Fessing","doi":"10.1111/exd.15100","DOIUrl":"10.1111/exd.15100","url":null,"abstract":"<p>Skin wound healing is driven by proliferation, migration and differentiation of several cell types that are controlled by the alterations in the gene expression programmes. Brahma Gene 1 (BRG1) (also known as SMARCA4) is a core ATPase in the BRG1 Associated Factors (BAF) ATP-dependent chromatin remodelling complexes that alter DNA-histone interaction in chromatin at the specific gene regulatory elements resulting in increase or decrease of the target gene transcription. Using siRNA mediated suppression of <i>BRG1</i> during wound healing in a human ex vivo and in vitro (scratch assay) models, we demonstrated that BRG1 is essential for efficient skin wound healing by promoting epidermal keratinocytes migration, but not their proliferation or survival. BRG1 controls changes in the expression of genes associated with gene transcription, response to wounding, cell migration and cell signalling. Altogether, our data revealed that BRG1 play positive role in skin repair by promoting keratinocyte migration and impacting the genes expression programmes associated with cell migration and cellular signalling.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yingrou Tan, Yuning Zhang, Jackson Liang Yao Li, Hui Yi Chia, Melissa Wee Ping Tan, Gernot Ebel, Keith Weng Kit Leong, Eiffer Ying Qi Lim, Kylia Kai Ling Chong, Bernett Teck Kwong Lee, Lai Guan Ng, Hong Liang Tey
{"title":"Visualising cancer in 3D: 3-Dimensional Tissue Imaging for management of cutaneous basal cell carcinoma","authors":"Yingrou Tan, Yuning Zhang, Jackson Liang Yao Li, Hui Yi Chia, Melissa Wee Ping Tan, Gernot Ebel, Keith Weng Kit Leong, Eiffer Ying Qi Lim, Kylia Kai Ling Chong, Bernett Teck Kwong Lee, Lai Guan Ng, Hong Liang Tey","doi":"10.1111/exd.15097","DOIUrl":"10.1111/exd.15097","url":null,"abstract":"<p>Surgical management of basal cell carcinoma (BCC) typically involves surgical excision with post-operative margin assessment using the bread-loafing technique; or gold-standard Mohs micrographic surgery (MMS), where margins are iteratively examined for residual cancer after tumour removal, with additional excisions performed upon detecting residual tumour at margins. There is limited sampling of resection margins with bread loafing, with detection of positive margins 44% of the time using 2 mm intervals. To resolve this, we have developed three-dimensional (3D) Tissue Imaging for: (1) complete examination of cancer margins and (2) detection of tumour proximity to nerves and blood vessels. 3D Tissue optical clearing with a light sheet imaging protocol was developed for margin assessment in two datasets assessed by two independent evaluators: (1) 48 samples from 29 patients with varied BCC subtypes, sizes and pigmentation levels; (2) 32 samples with matching Mohs' surgeon reading of tumour margins using two-dimensional haematoxylin & eosin-stained sections. The 3D Tissue Imaging protocol permits a complete examination of deeper and peripheral margins. Two independent evaluators achieved negative predictive values of 92.3% and 88.24% with 3D Tissue Imaging. Images obtained from 3D Tissue Imaging recapitulates histological features of BCC, such as nuclear crowding, palisading and retraction clefting and provides a 3D context for recognising normal skin adnexal structures. Concurrent immunofluorescence labelling of nerves and blood vessels allows visualisation of structures closer to tumour-positive regions, which may have a higher risk for neural and vascular infiltration. Together, this method provides more information in a 3D spatial context, enabling better cancer management by clinicians.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}