Squamous Cell Carcinoma: Biomarkers and Potential Therapeutic Targets

Squamous cell carcinoma (SCC) is the second most frequent non-melanoma skin cancer (NMSC) and carries with it a significant psychosocial and economic burden for both patients and health-care systems. Known risk factors for SCC include chronic ultraviolet (UV) exposure, chronic wounds and inflammation, exposure to certain chemicals and immunosuppression. The considerable risk of SCC recurrence and metastasis has driven the need for the discovery of new molecules that could explain the initiation and biological behavior of this type of NMSC. In this respect, proteomic research techniques have rapidly evolved and adapted in order to connect missing links and single out distinctive skin cancer biosignatures. Proteomic analysis of normal, dysplastic, and malignant keratinocytes appears to be promising in respect to SCC biomarker discovery, with the potential to aid in risk assessment, early detection, disease progression and development of novel targeted therapeutic agents. Identifying changes in the keratinocyte proteome pattern from normal to inflammatory and malignant cells will lead to the discovery of novel SCC biomarkers that could represent valuable tools for patient screening, diagnosis, management and follow-up

The dermoscopic rainbow pattern - a review of the literature

The “rainbow” pattern is a relatively new dermoscopic term that describes a bluish-reddish coloration together with various colors of the rainbow observable mainly through polarized light dermoscopy. Despite several theories, the rainbow pattern has not yet been clearly associated with any particular histological structure. This feature has been described in skin lesions with abundant vascularization such as Kaposi’s sarcoma, basal cell carcinoma, scars, squamous cell carcinoma, melanoma, and others. In this paper we conducted a review of the available studies regarding the appearance of the rainbow pattern in different pathologies. Furthermore, we present a detailed description of the physical phenomenon in order to obtain a better understanding of this peculiar dermoscopic feature. </p

Feasibility of Reflectance Confocal Microscopy Monitoring in Oily, Acne-Prone Facial Skin Treated with a Topical Combination of Alpha and Beta-Hydroxy Acids, Anti-Inflammatory Molecules, and Herculane Thermal Water: A Blinded, One-Month Study

Oily, acne-prone skin is a common skin type which may be monitored in vivo using reflectance confocal microscopy (RCM). The aim of the study was to assess the feasibility of RCM in evaluating the effectiveness of a topical combination of alpha- and beta-hydroxy acids, anti-inflammatory and antibacterial molecules, and Herculane thermal water on acne-prone skin. Thirty-five subjects with oily, acne-prone skin were prescribed topical combination products and were evaluated by clinical, Wood’s lamp, and RCM imaging at baseline and after 28 days. At 28 days, the RCM-evaluated number of dilated infundibula, infundibula filled with keratotic material, and infundibula with thickened bright borders, as well as the density of the inflammatory infiltrate, were significantly decreased. Wood’s light images at 28 days showed a significantly reduced number of C. acnes-colonized infundibula, and both the median area and the intensity of the red-orange fluorescence were decreased. The reduction in the clinical score was concurrent with the improvement in the RCM parameters, suggesting that this non-invasive imaging technique is appropriate for efficiency evaluations of topical acne treatments

Artificial Intelligence-Based Approaches to Reflectance Confocal Microscopy Image Analysis in Dermatology

Reflectance confocal microscopy (RCM) is a non-invasive imaging method designed to identify various skin diseases. Confocal based diagnosis may be subjective due to the learning curve of the method, the scarcity of training programs available for RCM, and the lack of clearly defined diagnostic criteria for all skin conditions. Given that in vivo RCM is becoming more widely used in dermatology, numerous deep learning technologies have been developed in recent years to provide a more objective approach to RCM image analysis. Machine learning-based algorithms are used in RCM image quality assessment to reduce the number of artifacts the operator has to view, shorten evaluation times, and decrease the number of patient visits to the clinic. However, the current visual method for identifying the dermal-epidermal junction (DEJ) in RCM images is subjective, and there is a lot of variation. The delineation of DEJ on RCM images could be automated through artificial intelligence, saving time and assisting novice RCM users in studying the key DEJ morphological structure. The purpose of this paper is to supply a current summary of machine learning and artificial intelligence&rsquo;s impact on the quality control of RCM images, key morphological structures identification, and detection of different skin lesion types on static RCM images

In Vivo Characterization of Mucin and Amyloid Deposits in Primary Basal Cell Carcinoma through Reflectance Confocal Microscopy: A Correlation with Histopathology

Basal cell carcinoma (BCC) is the most common keratinocyte carcinoma and the most prevalent skin cancer in humans, worldwide. BCC is histologically characterized by the proliferation of basaloid cells, arranged in globular masses of varying size, often separated from the surrounding stroma by optically empty spaces. Although attributed to tumor retraction during tissue processing for the preparation of pathology slides, these spaces are also seen on cryostat sections. The aim of this study is to in vivo characterize amyloid and mucin deposits in primary BCC lesions through RCM, followed by histopathological correlation. We included twenty-two consecutive subjects totaling thirty-one primary BCCs. Each lesion underwent the same evaluation protocol which included: clinical and dermoscopic images, RCM imaging, excisional biopsy under local anesthesia, and histopathological examination (colloidal iron and cytokeratin 34betaE12 stains). Hypo-reflective peritumoral clefts and hyper-reflective globules were measured on RCM images and compared to mucin and amyloid deposits seen on histology slides. The mean differences between RCM and histology measurements in both mucin and amyloid were not statistically significant. There were medium and strong correlations between RCM and histology regarding mucin and amyloid deposits, respectively

In Vivo Characterization of Mucin and Amyloid Deposits in Primary Basal Cell Carcinoma through Reflectance Confocal Microscopy: A Correlation with Histopathology

Basal cell carcinoma (BCC) is the most common keratinocyte carcinoma and the most prevalent skin cancer in humans, worldwide. BCC is histologically characterized by the proliferation of basaloid cells, arranged in globular masses of varying size, often separated from the surrounding stroma by optically empty spaces. Although attributed to tumor retraction during tissue processing for the preparation of pathology slides, these spaces are also seen on cryostat sections. The aim of this study is to in vivo characterize amyloid and mucin deposits in primary BCC lesions through RCM, followed by histopathological correlation. We included twenty-two consecutive subjects totaling thirty-one primary BCCs. Each lesion underwent the same evaluation protocol which included: clinical and dermoscopic images, RCM imaging, excisional biopsy under local anesthesia, and histopathological examination (colloidal iron and cytokeratin 34betaE12 stains). Hypo-reflective peritumoral clefts and hyper-reflective globules were measured on RCM images and compared to mucin and amyloid deposits seen on histology slides. The mean differences between RCM and histology measurements in both mucin and amyloid were not statistically significant. There were medium and strong correlations between RCM and histology regarding mucin and amyloid deposits, respectively

A Case of Multinucleate Cell Angiohistiocytoma with New Reflectance Confocal Microscopy Findings

Multinucleate cell angiohistiocytoma (MCAH) is a rare, benign, vascular or fibrohistiocytic tumor usually presenting as single or multiple, reddish-brown papules mostly affecting the limbs and dorsum of the hands of middle-aged females. Since 1985, relatively few MCAH cases have been reported. In vivo reflectance confocal microscopy (RCM) findings of MCAH have never been described. We report a case of MCAH with new non-invasive imaging findings through RCM in correlation with dermoscopy and histopathology. A 66-year-old woman with an unremarkable family and personal history of an atypical nevus presented with a lesion on her right breast. It had appeared 12 months earlier and progressively enlarged. Physical examination revealed a 20 &times; 11.6 mm, non-tender, reddish-brown maculo-papular lesion with blurred margins. Dermoscopy showed diffusely arranged reddish areas, coalescing whitish patches, truncated and dotted vessels, and a peripheral brown reticulated pattern. RCM revealed a poorly outlined lesion with a normal honeycomb pattern, numerous vessels at the dermal&ndash;epidermal junction, and isolated, large, mildly reflective, bizarre structures with angulated edges. These findings correlated well with histological features, which established the diagnosis of MCAH. Even though histopathology remains the gold standard in the diagnosis of MCAH, non-invasive tools such as RCM can help rule out other entities, therefore reducing surgery-associated morbidity

Preoperative Evaluation through Dermoscopy and Reflectance Confocal Microscopy of the Lateral Excision Margins for Primary Basal Cell Carcinoma

Complete removal of malignant skin lesions with minimal impact on the aesthetic and functional aspects is the ideal of every dermatologic surgeon. Incomplete surgical excisions and tumor recurrences of basal cell carcinomas (BCC) commonly occur due to the subclinical extension of tumor lateral margins. Presently, the lateral excision margins for BCC cannot be objectively assessed preoperatively, dermoscopy proving to be relatively inefficient in this respect. The question is whether BCC lateral excision margins can be precisely determined preoperatively through the use of complementary non-invasive imaging techniques such as dermoscopy and reflectance confocal microscopy (RCM), thus permitting the complete removal of the lesion in a single stage, estimation of the post-excisional defect, and planning an appropriate reconstruction, especially in medical centers where Mohs micrographic surgery is not available. We present the results of a prospective, histopathologically controlled study designed to determine the feasibility of preoperative, non-invasive, in vivo evaluation of the lateral excision margins for primary basal cell carcinoma, through dermoscopy and RCM

Preoperative Evaluation through Dermoscopy and Reflectance Confocal Microscopy of the Lateral Excision Margins for Primary Basal Cell Carcinoma

Complete removal of malignant skin lesions with minimal impact on the aesthetic and functional aspects is the ideal of every dermatologic surgeon. Incomplete surgical excisions and tumor recurrences of basal cell carcinomas (BCC) commonly occur due to the subclinical extension of tumor lateral margins. Presently, the lateral excision margins for BCC cannot be objectively assessed preoperatively, dermoscopy proving to be relatively inefficient in this respect. The question is whether BCC lateral excision margins can be precisely determined preoperatively through the use of complementary non-invasive imaging techniques such as dermoscopy and reflectance confocal microscopy (RCM), thus permitting the complete removal of the lesion in a single stage, estimation of the post-excisional defect, and planning an appropriate reconstruction, especially in medical centers where Mohs micrographic surgery is not available. We present the results of a prospective, histopathologically controlled study designed to determine the feasibility of preoperative, non-invasive, in vivo evaluation of the lateral excision margins for primary basal cell carcinoma, through dermoscopy and RCM

A Systematic Review and Meta-Analysis of the Accuracy of in Vivo Reflectance Confocal Microscopy for the Diagnosis of Primary Basal Cell Carcinoma

Basal cell carcinoma (BCC) is the most common cancer worldwide and its incidence is constantly rising. Early diagnosis and treatment can significantly reduce patient morbidity and healthcare costs. The value of reflectance confocal microscopy (RCM) in non-melanoma skin cancer diagnosis is still under debate. This systematic review and meta-analysis were conducted to assess the diagnostic accuracy of RCM in primary BCC. PubMed, Google Scholar, Scopus, and Web of Science databases were searched up to July 05, 2019, to collect articles concerning primary BCC diagnosis through RCM. The studies&rsquo; methodological quality was assessed by the QUADAS-2 tool. The meta-analysis was conducted using Stata 13.0, RevMan 5.0, and MetaDisc 1.4 software. We included 15 studies totaling a number of 4163 lesions. The pooled sensitivity and specificity were 0.92 (95% CI, 0.87&ndash;0.95; I2 = 85.27%) and 0.93 (95% CI, 0.85&ndash;0.97; I2 = 94.61%), the pooled positive and negative likelihood ratios were 13.51 (95% CI, 5.8&ndash;31.37; I2 = 91.01%) and 0.08 (95% CI, 0.05&ndash;0.14; I2 = 84.83%), and the pooled diagnostic odds ratio was 160.31 (95% CI, 64.73&ndash;397.02; I2 = 71%). Despite the heterogeneity and risk of bias, this study demonstrates that RCM, through its high sensitivity and specificity, may have a significant clinical impact on the diagnosis of primary BCC