Reflectance Confocal Microscopy Research Articles

Eruptive pseudoangiomatosis and parvovirus: exclusive clinical findings

Introduction: Eruptive pseudoangiomatosis (EP) is a rare type of cutaneous exanthema characterized by red angioma-like papules. An association of EP with viral infection has been reported. We herein describe four pediatric patients who showed a new variant of EP-associated rash with atypical clinical features and positivity for parvovirus B19 infection. Case Report: Pediatric patients showed a new variant of EP-associated rash with atypical clinical features and positivity for parvovirus B19 infection by dermoscopy and reflectance confocal microscopy. The papules were localized to the face and characteristic perilesional halo was absent. In all patients, serology revealed evidence of active infection by parvovirus B19. Discussion: Few cases of a facial pseudoangiomatous rash that is related to parvovirus B19 infection and lacks the typical anemic halo have been reported in the literature. Conclusion: These cases provide new data on the clinical spectrum of EP and its association with parvovirus.

Dermoscopy and reflectance confocal microscopy of solitary flat pink lesions: A new combined score to diagnose amelanotic melanoma.

Differential diagnosis of amelanotic/hypomelanotic melanoma among solitary flat pink lesions is challenging, due to limited clinical and dermoscopic clues. Dermoscopy and reflectance confocal microscopy assessments improve diagnostic accuracy, but their combined capacity among solitary flat pink lesions is yet to be defined. To determine (i) whether diagnostic accuracy is improved with combined dermoscopy and reflectance confocal microscopy, (ii) a model to estimate probability of flat amelanotic/hypomelanotic melanoma among solitary flat pink lesions. A retrospective single-centre study of solitary flat pink lesions, excised for suspected malignancy between 2011 and 2022 was performed. Images were independently evaluated by two dermatologists, blinded to histopathological diagnosis. Diagnostic performance was evaluated on the receiver operating characteristic curve and the area under the curve. Predictive features were identified by univariate and multivariate logistic regression analyses. A final predictive nomogram of independent risk factors was calculated by backward likelihood ratio. Hypothesis being tested was formulated before data collection. A total of 184 patients (87 females, 47.3%) were included; mean age was 57.6 years (19-95). Combined dermoscopy and reflectance confocal microscopy was more sensitive (83%, CI 69.2-92.4 and 91.5%, CI 79.6-97.6) than dermoscopy alone (76.6%, CI 62.0-87.7 and 85.1%, CI 71.7-93.8). Predictive features defined the new model, including linear irregular vessels (4.26-folds, CI 1.5-12.1), peripheral pigment network (6.07-folds, CI 1.83-20.15), remnants of pigmentation (4.3-folds, CI 1.27-14.55) at dermoscopy and atypical honeycomb (9.98-folds, CI 1.91-51.96), disarranged epidermal pattern (15.22-folds, CI 2.18-106.23), dendritic pagetoid cells in the epidermis (3.77-folds, CI 1.25-11.26), hypopigmented pagetoid cells (27.05-folds, CI 1.57-465.5), and dense and sparse nests (3.68-folds, CI 1.24-10.96) in reflectance confocal microscopy. Diagnostic accuracy of the model was high (AUC 0.91). Adjunctive reflectance confocal microscopy increases diagnostic sensitivity of flat amelanotic/hypomelanotic melanoma differential diagnosis. The proposed model requires validation.

Available medical imaging modalities for melanoma screening

The prevalence of melanoma of the skin has seen a significant rise in recent decades, constituting approximately one-third of all diagnosed cancer cases. Melanoma, the most fatal variant among cutaneous malignancies, exhibits a 4% probability of occurrence over an individual’s lifetime. The increasing incidence and mortality rates of skin cancer impose a substantial burden on healthcare resources and the economy. In recent years, several optical modalities, including dermoscopy, reflectance confocal microscopy (RCM), optical coherence tomography, multiphoton excited fluorescence imaging, and dermatofluorescence, have been extensively studied and utilized to improve the non-invasive diagnosis of skin cancer. This review article provides an analysis of the approach employed in the recently developed optical non-invasive diagnostic technologies. It explores the clinical uses of these techniques, while also examining their respective advantages and disadvantages. Furthermore, the paper explores the possibility for additional advancements in these technologies in the future.

Film-Forming, Moisturizing, and Sensory Properties of a Cosmetic Formulation Containing Tara Gum and Brazilian Berry Extracts.

The development of cosmetic formulations with moisturizing and film-forming properties has been very important to help keep skin physiology and protection. In this context, this study aimed to develop a cosmetic formulation containing Tara gum and Brazilian berry extract and evaluate its physical-mechanical, film-forming, and sensory properties. A gel formulation was developed based on Tara gum added to Plinia cauliflora extract and was characterized by its spreadability profile and sensory properties. A clinical study was carried out with ten participants to evaluate the skin microrelief, stratum corneum water content, transepidermal water loss (TEWL), and skin morphological characteristics by reflectance confocal microscopy (RCM) before and after 2h of application of the formulations. The formulation with Brazilian berry significantly decreased the work of shear parameter, which can be correlated with improved spreadability in the sensory analysis. The clinical study showed that both formulations improved skin hydration and reduced the TEWL. The RCM imaging analysis showed the visible film on the skin surface, a decrease in the size of furrows, an increase in the reflectance of the interkeratinocytes, and reflectance of the stratum corneum for both formulations. These results were more pronounced for the formulation containing Brazilian berry. The Tara gum in the gel formulation promoted the formation and visualization of a polymeric net on the stratum corneum surface, demonstrated by the images obtained from RCM. However, the formulation added with the Brazilian berry extract improved the skin microrelief, honeycomb pattern of the epidermis, and skin hydration in deeper layers of the epidermis.

A Prospective Double-Blinded Comparison of Reflectance Confocal Microscopy with Conventional Histopathology for In Vivo Assessment in Oral Cancer.

We investigated reflectance confocal microscopy (RCM) as a possible non-invasive approach for the diagnosis of cancer and real-time assessment of surgical margins. In a phase I study on 20 patients, we established the RCM imaging morphological features that distinguish OSCC from normal tissue with a newly developed intra-oral RCM probe. Our subsequent phase II prospective double-blinded study in 60 patients tested the diagnostic accuracy of RCM against histopathology. Five RCM videos from the tumor and five from normal surrounding mucosa were collected on each patient, followed by a 3-mm punch biopsy of the imaged area. An experienced RCM reader, who was blinded to biopsy location and histological diagnosis, examined the videos from both regions and classified each as "tumor" or "not-tumor" based on RCM features established in phase I. Hematoxylin and eosin slides from the biopsies were read by a pathologist who was blinded to RCM results. Using histology as the gold standard, we calculated the sensitivity and specificity of RCM. We report a high agreement between the blinded readers (95% for normal tissue and 81.7% for tumors), high specificity (98.3%) and negative predictive values (96.6%) for normal tissue identification, and high sensitivity (90%) and positive predictive values (88.2%) for tumor detection. RCM imaging is a promising technology for non-invasive in vivo diagnosis of OSCC and for real-time intraoperative evaluation of mucosal surgical margins. Its inherent constraint, however, stems from the diminished capability to evaluate structures located at more substantial depths within the tissue.

Abstract 4171: Utilizing biopsy-free virtual histology for improved clinical efficiency in the dermatologic surgical setting

Abstract The ability to accurately define tumor margins may enhance tissue sparing and increase efficiency in the dermatologic surgery process, but no device exists that serves this role. Reflectance Confocal Microscopy (RCM) provides non-invasive cellular resolution of the skin. The only clinically-approved RCM device is bulky, non-portable, and requires a tissue cap which makes mapping of the underlying tissue impossible. We recently combined “virtual histology”, a machine learning algorithm with RCM images from this standard RCM device to generate biopsy-free histology to overcome these limitations. Whether virtual histology can be used with a portable, handheld RCM device to scan for residual tumor and tumor margins is currently unknown. We hypothesize that combining a handheld RCM device with virtual histology could provide accurate tumor margin assessment. We determined whether our established virtual histology algorithm could be applied to images from a portable RCM device and whether these pseudo-stained virtual histology images correlated with histology from skin specimens. The study was conducted as a prospective, consecutive non-randomized trial at a Veterans Affairs Medical Center dermatologic surgery clinic. All patients greater than 18 years of age with previously biopsied BCC, SCC, or SCCis were included. Successive confocal images from the epidermis to the dermis were obtained 1.5 microns apart from the handheld RCM device to detect residual skin cancer. The handheld, in-vivo RCM images were processed through a conditional generative adversarial network-based machine learning algorithm to digitally convert the images into H&E pseudo-stained virtual histology images. Virtual histology of in-vivo RCM images from unbiopsied skin captured with the portable RCM device were similar to those obtained with the standard RCM device and virtual histology applied to portable RCM images correctly correlated with frozen section histology. Residual tumors detected with virtual histology generated from the portable RCM images accurately corresponded with residual tumors shown in the frozen surgical tissue specimen. Residual tumor was also not detected when excised tissue was clear of tumor following surgical procedure. Thus, the combination of virtual histology with portable RCM may provide accurate histology-quality data for evaluation of residual skin cancer prior to surgery. Combining machine learning-based virtual histology with handheld RCM images demonstrates promise in providing insights into tumor characteristics and has the potential to assist the surgeon and better guide practice decisions to more efficiently serve patients, leading to decreased layers and appointment times. Future work is needed to provide real time virtual histology, convert horizontal/confocal sections into vertical or 3D sections, and to perform clinical studies to map tumors in tissue. Citation Format: Rachel Wahhab, Nelly Kokikian, Jingxi Li, Jason Garfinkel, Stephanie Martin, David Beynet, Aydogan Ozcan, Philip Scumpia. Utilizing biopsy-free virtual histology for improved clinical efficiency in the dermatologic surgical setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4171.

Abstract 4269: Effect of PAX3-FOXO1 fusion gene on cell-extracellular matrix interaction of Rhabdomyosarcoma

Abstract Background Rhabdomyosarcoma (RMS) is the most common childhood soft tissue sarcoma, categorized by two subtypes, fusion protein-positive (FPRMS) and negative (FNRMS), based on the existence of PAX3-FOXO1 fusion gene (P3F). Different features between the two subtypes could guide the use of distinct treatment approaches. We discovered that FNRMS exhibited enrichment of gene sets related to cell-extracellular matrix (ECM) interaction than FPRMS. ECM, providing physical support as a scaffold, regulates cancer development. We hypothesize that a distinct molecular feature, P3F, may cause the difference in cell-ECM interaction between FPRMS and FNRMS. Methods To confirm the higher cell-ECM interaction of FNRMS vs. FPRMS, we used confocal reflection microscopy (CRM), enabling us to monitor the fibrous structures of ECM. We generated the spheroids with FNRMS and FPRMS cell lines by hanging drop method and embedded them into collagen type I. Then, we assessed orientation and dynamic changes in the structure of collagen fibers surrounding spheroids. Also, we analyze the transcriptome of FPRMS cells with P3F knockdown to confirm if P3F regulates cell-ECM interaction negatively via RNA seq. Additionally, we examined ECM surrounding spheroids of P3F knockdown FPRMS cells if P3F modulates fibrous structures of ECM, indicating cell-ECM interaction. Results We showed that collagen fibers are oriented more perpendicular to the FNRMS spheroid surface, indicating the strong pulling and pushing effect of cells. However, fibers surrounding FPRMS spheroids showed parallel alignment to their surfaces, reflecting passively pushed by the spheroids. Additionally, fibers near FNRMS spheroids showed greater displacement than those near FNRMS spheroids, which suggests stronger cell-ECM interaction in FNRMS than in FPRMS. Furthermore, P3F knockdown FPRMS cells exhibited significant enrichment of gene sets related to cell-ECM interaction. Their CRM results showed that collagen fiber orientation was significantly perpendicular to the surfaces of spheroids of P3F knockdown FPRMS cells than those of control cells. P3F knockdown cell spheroids also displayed enhanced displacement of ECM fibers than control cells. These results suggest that P3F suppresses cell-ECM interaction, consistent with higher cell-ECM interaction of FNRMS than FPRMS. Conclusions The PAX3-FOXO1 gene may regulate cell-ECM interaction negatively, causing distinct features between FPRMS and FNRMS, which is crucial for various cellular functions and suggest different treatment between the two RMS subtypes. Citation Format: Chandra Kaladhar Vemula, Ivan Chavez, Anthony Chronopoulos, Jinseok Park. Effect of PAX3-FOXO1 fusion gene on cell-extracellular matrix interaction of Rhabdomyosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4269.

Exploring the Utilization of Imaging Modalities in the Diagnosis of Basal Cell Carcinoma: A Scoping Review.

Basal cell carcinoma (BCC) is a common skin cancer that occurs due to various genetic and environmental factors. Diagnosis is made by a combination of clinical appearance, biopsy, imaging, and histopathological analysis. This review describes the current array of imaging modalities available to physicians to aid in the diagnosis of BCC. It is important to stay up-to-date with improvements in diagnostic screening, and knowledge of these options is instrumental in providing the best care to patients. Embase, Medline Industries, and PubMed were searched for articles within the past 10 years based on a search query that looked for imaging modalities used in the diagnosis and evaluation of a variety of dermatologic conditions. The search was further refined to focus on BCC and satisfy the inclusion/exclusion criteria determined by the authors. The research process was detailed in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses diagram. Dermoscopy is a non-invasive in vivo microscopic technique used to evaluate skin lesions. Features of dermoscopy cannot be visualized with the naked eye, and studies found that dermoscopy increased diagnostic accuracy. Reflectance confocal microscopy (RCM) examines skin morphology, and recent studies found that 100% of patients with BCC had tumor-free margins when diagnosed with RCM. It allows for a one-stop-shop for diagnosis. Optical spectroscopy samples multiple sites without removing tissue. It helps detect subtle biophysical differences, allowing for earlier diagnosis. High-frequency ultrasound (HFUS) helps determine tumor size, structure, depth of invasionand spread. Studies found statistically significant positive correlations between depth of spread and HFUS readings. Optical coherence tomography takes cross-sectional images to analyze histopathology and morphology. It produces high-resolution images, confers slightly more accurate results than a biopsy, and expedites the treatment process through an earlier diagnosis without a biopsy.These results will advance the fields of dermatology and radiology as they describe unique uses for these imaging modalities. There are a variety of ways to use microscopy, and these techniques may be applied to many different lesions and help revolutionize the diagnosis and treatment of skin cancer and other lesions without the need for multiple, sometimes disfiguring surgical procedures. With the increase in diagnostic accuracy and decrease in diagnosis time, advanced imaging studies will become an integral part of dermatologic diagnosis and be included in future management and treatment plans, especially in the case of BCC.

Diagnosis and therapy of actinic keratosis.

Actinic keratosis (AK) is considered a chronic and recurring in situ skin neoplasia, with a possible transformation into invasive squamous cell carcinoma (SCC). Among others, predominant risk factors for development of AK are UV-light exposure and immunosuppression. Basal epidermal keratinocyte atypia (AK I) and proliferation (PRO score) seem to drive malignant transformation, rather than clinical appearance of AK (Olsen I-III). Due to the invasiveness of punch biopsy, those histological criteria are not regularly assessed. Non-invasive imaging techniques, such as optical coherence tomography (OCT), reflectance confocal microscopy (RCM) and line-field confocal OCT (LC-OCT) are helpful to distinguish complex cases of AK, Bowen's disease, and SCC. Moreover, LC-OCT can visualize the epidermis and the papillary dermis at cellular resolution, allowing real-time PRO score assessment. The decision-making for implementation of therapy is still based on clinical risk factors, ranging from lesion- to field-targeted and ablative to non-ablative regimens, but in approximately 85% of the cases a recurrence of AK can be observed after a 1-year follow-up. The possible beneficial use of imaging techniques for a non-invasive follow-up of AK to detect recurrence or invasive progression early on should be subject to critical evaluation in further studies.

Melasma and reflectance confocal microscopy: from baseline to treatment monitoring.

Melasma is a frequent condition worldwide, and it represents one of the most challenging disorders to treat in cosmetic dermatology. One of the critical factors for treatment prognosis is the assessment of the depth and distribution of pigment within the hyperpigmented area. Nowadays, non-invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to estimate pigment distribution and depth within different skin layers. This article aims to provide a systematic review of RCM applications in melasma, providing terminology and investigating characteristics of melasma at baseline and after medical and laser treatment. Our results support the recognition of two main types of melasma, epidermal and mixed type, thanks to the role of RCM in highlighting the precise pigment depth location in the skin non-invasively. RCM treatment monitoring enables the objectification of pigment variations after treatment and the identification of prognostic factors for different treatment modalities. After the era of the application of RCM as a technique applied strictly to skin cancers, additional cosmetic applications are emerging, such as the application of melasma treatment monitoring.

Features of tattoo-associated cutaneous lymphoid hyperplasia on reflectance confocal microscopy and line-field confocal optical coherence tomography.

The popularity of tattoos has led to an increase in associated skin reactions, including complications such as infection, allergic reactions and rare conditions such as tattoo-induced cutaneous lymphoid hyperplasia (CLH). CLH is a benign lymphoproliferative reaction with clinical features resembling malignant cutaneous lymphomas. Non-invasive diagnostic tools like reflectance confocal microscopy (RCM) and the new line-field confocal optical coherence tomography (LC-OCT) are being studied in dermatology better to understand the morphological patterns of many dermatological diseases. Between September 2021 and May 2023, patients with suspicious lesions for tattoo-related CLH were analysed using RCM and LC-OCT before confirming the diagnosis of CLH through skin biopsy and histopathological examination. The study included five cases of CLH. It focused on the analysis of high-quality LC-OCT images/videos and RCM images to investigate the features of CLH in tattooed individuals. Most (80%) cases exhibited a mixed T and B lymphocyte infiltration subtype, while 20% showed a predominant T infiltration subtype. RCM and LC-OCT revealed characteristic features, including architectural disarray, fibrosis, lymphoid infiltrates, and pigment deposits in the epidermis and dermis. Non-invasive tools such as RCM and LC-OCT are valuable in diagnosing tattoo-related CLH. While skin biopsy remains the current standard for diagnosis, RCM and LC-OCT can serve as helpful adjuncts in identifying the most representative area for biopsy. They may potentially become alternative diagnostic options in the future, offering benefits in terms of cost, diagnostic efficiency, aesthetics and patient satisfaction as the prevalence of tattoo-related adverse reactions continues to rise.

Non-Invasive Imaging for the Diagnosis of Genital Warts and Their Imitators.

Genital warts are the most frequent sexually transmitted disease. Their clinical diagnosis is not always easy, and invasive skin biopsies for histological examination should be performed in these cases. The aim of the study was to investigate the use of non-invasive imaging techniques for the diagnosis of genital warts and their imitators. We retrospectively evaluated dermoscopy, reflectance confocal microscopy (RCM), and line-filed confocal microscopy (LC-OCT) images of nine patients with 19 warts of the mucous membranes and five patients with lesions that clinically mimic genital warts, including 12 molluscum contagiosum, 1 Fordyce's spot and one case of multiple acquired lymphangiomas. Most genital warts (15; 79%) showed dilated vessels surrounded by a whitish halo at dermoscopy. RCM and the new device LC-OCT could identify near histologic features such as the presence of hyperkeratosis, acanthosis, papillomatosis and enlarged vessels in all genital warts. However, the identification of koilocytes, which are the hallmark for the diagnosis of warts, was still difficult using both techniques. Non-invasive imaging techniques could also offer clues for the correct diagnosis of the imitators. This study confirmed the usefulness of dermoscopy in recognizing a precise pattern in warts and showed the potential use of RCM and LC-OCT to add additional findings to the clinical and dermoscopic examination.

Phase contrast reflectance confocal brain imaging at 1650nm.

The imaging depth of microscopy techniques is limited by the ability of light to penetrate biological tissue. Recent research has addressed this limitation by combining a reflectance confocal microscope with the NIR-II (or shortwave infrared) spectrum. This approach offers significant imaging depth, is straightforward in design, and remains cost-effective. However, the imaging system, which relies on intrinsic signals, could benefit from adjustments in its optical design and post-processing methods to differentiate cortical cells, such as neurons and small blood vessels. We implemented a phase contrast detection scheme to a reflectance confocal microscope using NIR-II spectral range as illumination. We analyzed the features retrieved in the images while testing the imaging depth. Moreover, we introduce an acquisition method for distinguishing dynamic signals from the background, allowing the creation of vascular maps similar to those produced by optical coherence tomography. The phase contrast implementation is successful to retrieve deep images in the cortex up to using a cranial window. Vascular maps were retrieved at similar cortical depth and the possibility of combining multiple images can provide a vessel network. Phase contrast reflectance confocal microscopy can improve the outlining of cortical cell bodies. With the presented framework, angiograms can be retrieved from the dynamic signal in the biological tissue. Our work presents an optical implementation and analysis techniques from a former microscope design.

Vitiligo Treated with Combined Piperine-Based Topical Treatment and Narrowband Ultraviolet B Therapy: Follow-Up with Reflectance Confocal Microscopy.

Reflectance confocal microscopy (RCM) has a defined in vivo morphology of vitiligo and re-pigmentation. Combination therapies seem more effective than monotherapies. We aim to describe the clinical and RCM features of re-pigmentation with combined narrowband ultraviolet B (NB-UVB) and piperine-based topical treatment in localized vitiligo. Eight patients enrolled at a single center received combined treatment: topical treatment was applied twice daily + NB-UVB twice weekly for 2 × 2-month periods. Clinical changes were analyzed by the Vitiligo Noticeability Scale (VNS) and percentage of re-pigmentation. The evaluator agreement was assessed. Predefined RCM features had the presence/absence of (i) blood vessels, (ii) dendritic cells, and the quantity of (i) an irregular honeycombed pattern and (ii) non-pigmented papillae. Clinical and RCM monitoring was performed at the baseline, 2, 3, 5, and 7 months. Macules were "slightly less noticeable" with 25-50% re-pigmentation. Irregular honeycomb patterns and non-pigmented papillae were significantly less frequently observed, and in less extended areas (T1 vs. T2, p = 0.039; T0 vs. T1, p = 0.005 and T2 vs. T4, p = 0.033). Dendritic cells and blood vessels improved, with significant changes in blood vessels (T1 vs. T2, p = 0.005 and T3 vs. T4, p = 0.008). RCM confirms the morphological changes induced by combined treatment for localized vitiligo.

Periocular sebaceous carcinoma: updates in the diagnosis, treatment, staging, and management.

Periocular sebaceous carcinoma (PSC) is a rare, aggressive, and potentially metastatic adnexal malignancy. Due to the ability of PSC to resemble several benign and malignant conditions, diagnosis is often delayed or mistaken. In addition, even with a known diagnosis, choosing the right treatment is still an open debate. For this reason, we decided to review the most up-to-date literature on PSC and propose a dedicated procedural protocol to help clinicians when dealing with PSC. A PubMed search was carried out using the terms "Sebaceous Carcinoma", "Adnexal Periocular Cancer", "Sebaceous Carcinoma AND eyelid", "Periocular Sebaceous Carcinoma", and "Ocular Adnexa". Pertinent studies published in English from 1997 up to December 2022 were compared to the selection criteria and if suitable, included in this review. Through the initial search, 84 articles were selected. Of these, 36 were included in the final study. Several papers explored different diagnostic and therapeutic strategies regarding PSC diagnosis and management. In light of the current literature review and the multidisciplinary experience of three clinical centers, a dedicated procedural protocol is proposed. PSC diagnosis may be achieved through accurate clinical evaluation, but it requires histopathologic confirmation, which can be challenging. Dermoscopy, in vivo reflectance confocal microscopy, and optical coherence tomography may facilitate PSC clinical examination, while immunohistochemistry stains may support histological diagnosis. Appropriate disease staging is necessary before choosing the treatment, as local disease requires radically different treatment compared to advanced disease. In addition, recent innovations in nonsurgical treatments, including radio-chemotherapy, immunotherapy, and targeted therapy, may be a viable option in the most challenging cases.

Utilization of Imaging Modalities in the Diagnosis of Melanoma: A Scoping Review.

Melanomas arise de novo or in the context of a precursor lesion. Lesions typically grow radially and then undergo a vertical growth phase proceeding to local invasion and metastasis. This review describes the utility of different imaging modalities in diagnosis and melanocytic lesion monitoring. A literature search was performed in November 2023 utilizing EMBASE, Medline, and PubMed. The PRISMA diagram demonstrates the review process. Reflectance confocal microscopy (RCM) utilizes near-infrared light to help diagnose dermatologic lesions. RCMwas found to demonstrate nearly two times the positive predictive value compared to dermoscopy. The introduction of the Berlin Ultrasound (US) Morphology Criteria permitted a 65-80% improvement in diagnostic sensitivity. US with fine-needle aspiration cytology (FNAC) accurately predicts the necessity for sentinel lymph node biopsy and lymphadenectomy, sparing patients with metastasis and prompting biopsy for equivocal lesions. Single-photon emission computed tomography/computed tomography (SPECT/CT) is an adjunctive tool to anatomically and functionally assess lymphatic invasion. SPECT/CT improves the detection of sentinel nodes while decreasing operating time and improving cosmetic outcomes. 18F-fluorodeoxyglucose(18F-FDG) positron emission tomography/computed tomography (PET/CT) with small voxel reconstruction demonstrated increased specificity and sensitivity for detecting in-transit metastases of melanomas, specifically in the limbs. Dermoscopy allows providers to cost-effectively recognize common lesion patterns. Multiphoton microscopy assigns a weight-based score based on malignant features. Optical coherence angiography captures images of vessels to help diagnose equivocal lesions. Utilization of imaging techniques may increase diagnostic accuracy, reduce unnecessary procedures, and help guide treatment plans. Additional research is needed to further characterize the utility of these techniques in order to improve the diagnosis and treatment of melanomas.

Diagnostic Imaging of Agminated Blue Lesions and Blue Lesions with Satellitosis: Case Series with a Concise Review of the Current Literature

Background: Agmination and/or satellitosis in pigmented blue lesions is a phenomenon rarely mentioned in the literature and not well known. This phenomenon can be expressed by several benign and malignant pigmented blue lesions, such as blue nevi, Spitz nevi, melanocytoma and melanoma. On this spectrum, dermoscopy, reflectance confocal microscopy (RCM) and dynamic Optical coherence tomography (D-OCT) represent non-invasive imaging technologies, which may help clinicians in the diagnosis of melanoma and non-melanoma skin cancers in daily clinical practice. Methods: Currently, in the literature there is a lack of new data about agminated blue lesions and blues lesions with satellitosis, as well as the lack of a recent and updated review of the literature about this topic. Therefore, considering that clinicians must be confident with the diagnosis of these rare skin lesions, we decided to carry out this work. Results: In this paper, four new cases of agminated pigmented cutaneous lesions were described. Moreover, a review of the current literature on this topic was performed. Conclusions: A clinical–pathological correlation is often needed to reach a correct diagnosis; currently, dermoscopy and non-invasive diagnostic techniques, such as reflectance confocal microscopy and optical coherence tomography, due to the depth of these skin lesions in the dermis, can only make a partial and limited contribution.

Real-life practice of reflectance confocal microscopy in France: A prospective multicenter study

BackgroundStudies demonstrating the potential utility of reflectance confocal microscopy (RCM) have been performed under experimental conditions. ObjectiveTo provide an overview of RCM practice in real-life. MethodsA multicenter, prospective study carried out in 10 university dermatology departments in France. Results0verall, 410 patients were enrolled. Half of the patients (48%) were referred by private-practice dermatologists. They were referred for diagnosis (84.9%) or pre-surgical mapping (13%). For diagnosis, the lesions were located on the face (62%), arms and legs (14.9%), and trunk (13,6%), and pre-surgical mapping was almost exclusively on the face (90.9%). Among those referred for diagnosis, the main indication was suspicion of a skin tumor (92.8%). Of these,50.6% were spared biopsies after RCM. When RCM indicated surgery, histology revealed malignant lesions in 72.7% of cases. The correlation between RCM and histopathology was high, with a correlation rate of 82.76% and a kappa coefficient of 0.73 (0.63; 0.82). Limitations: This study was performed in the settings of French tertiary referral hospitals. Conclusion: This study shows that in real-life RCM can be integrated into the workflow of a public private network, which enables a less invasive diagnostic procedure for patients.

Evaluation of linear dermatoses by reflectance confocal microscopy in children.

Lichen striatus (LS), linear psoriasis (LPs), linear cutaneous lupus erythematosus (LCLE) and linear lichen planus (LLP) often have similar clinical manifestations, which makes clinical diagnosis with the naked eye difficult; therefore, they are easily misdiagnosed. The purpose of this study was to determine whether reflectance confocal microscopy (RCM) is helpful in differentiating between these four linear dermatoses in children. This retrospective study included 14 patients with LS, nine with LPs, eight with LCLE and 12 with LLP. All patients were analysed using RCM, and biopsies were collected from lesions previously imaged by RCM. For LS, the dermal papillary rings were partially absent, but when present, manifested with small, homogeneously round, bright cells and occasionally highly refractive plump cellular structures, aggregated in clusters. LPs exhibited dark cyst-like structures with small, bright, round cells aggregated at the epidermal level; at the dermal-epidermal junction, homogeneously distributed, enlarged, faint dermal papillary rings and numerous enlarged low-refractive canalicular structures were observed in the superficial dermis. LCLE and LLP exhibited similar manifestations, including epidermal disarray, almost total absence of dermal papillary rings, and various sized refractive structures densely distributed in the dermis. The key distinguishing features of LCLE were the different sized structures mainly clustered around hair follicles, while LLP demonstrated dense structures with a scattered distribution. RCM may be used to distinguish between the key features of LS, LPs, LCLE and LLP in children.

Artificial Intelligence Applied to Non-Invasive Imaging Modalities in Identification of Nonmelanoma Skin Cancer: A Systematic Review

Background: The objective of this study is to systematically analyze the current state of the literature regarding novel artificial intelligence (AI) machine learning models utilized in non-invasive imaging for the early detection of nonmelanoma skin cancers. Furthermore, we aimed to assess their potential clinical relevance by evaluating the accuracy, sensitivity, and specificity of each algorithm and assessing for the risk of bias. Methods: Two reviewers screened the MEDLINE, Cochrane, PubMed, and Embase databases for peer-reviewed studies that focused on AI-based skin cancer classification involving nonmelanoma skin cancers and were published between 2018 and 2023. The search terms included skin neoplasms, nonmelanoma, basal-cell carcinoma, squamous-cell carcinoma, diagnostic techniques and procedures, artificial intelligence, algorithms, computer systems, dermoscopy, reflectance confocal microscopy, and optical coherence tomography. Based on the search results, only studies that directly answered the review objectives were included and the efficacy measures for each were recorded. A QUADAS-2 risk assessment for bias in included studies was then conducted. Results: A total of 44 studies were included in our review; 40 utilizing dermoscopy, 3 using reflectance confocal microscopy (RCM), and 1 for hyperspectral epidermal imaging (HEI). The average accuracy of AI algorithms applied to all imaging modalities combined was 86.80%, with the same average for dermoscopy. Only one of the three studies applying AI to RCM measured accuracy, with a result of 87%. Accuracy was not measured in regard to AI based HEI interpretation. Conclusion: AI algorithms exhibited an overall favorable performance in the diagnosis of nonmelanoma skin cancer via noninvasive imaging techniques. Ultimately, further research is needed to isolate pooled diagnostic accuracy for nonmelanoma skin cancers as many testing datasets also include melanoma and other pigmented lesions.