M. Peppelman

In vivo Diagnosis of Basal Cell Carcinoma Subtype by Reflectance Confocal Microscopy

Background: Reflectance confocal microscopy (RCM) is a noninvasive imaging technique. Currently, RCM is mainly used for the diagnosis of melanoma and nonmelanoma skin cancer including basal cell carcinoma (BCC). Until now, it has not been possible to distinguish between subtypes of BCC using RCM. Objective: To establish the RCM features for subtypes of BCC. Methods: 57 lesions were selected for RCM imaging. Clinical and dermatoscopic pictures were taken and a 3-mm biopsy was obtained. Results: It was demonstrated that tumor nests with peripheral palisading, branch-like structures, fibrotic septa and increase in vascular diameter were characteristic RCM features for nodular and micronodular BCC. The size and shape of the tumor nests allowed further distinction between these BCCs. Solar elastosis and tumor nests connected with the basal cell layer characterize superficial BCC. Conclusion: This study presents RCM features for BCC, which might allow in vivo diagnosis of the nodular, micronodular and superficial subtype of BCC. This could prevent a skin biopsy, resulting in direct proper treatment. Further, RCM allows to evaluate the total lesion, which makes it possible to detect mixed-type BCCs.

The value of in vivo reflectance confocal microscopy in the diagnosis and monitoring of inflammatory and infectious skin diseases: a systematic review

In vivo examination of the skin by reflectance confocal microscopy (RCM) has been performed for about 20 years, leading to a broad spectrum of imaged infectious and inflammatory skin diseases (ISD) with many described RCM features. We systematically reviewed all available literature concerning ISD evaluated by RCM. Furthermore, we assessed the accuracy of the features and defined recommendations for future studies after indicating the limitations in the current published literature. PubMed, Embase, Cochrane Library and Web of Science databases were searched for literature. All studies on RCM and ISD were reviewed and quality assessment was determined by using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist. The literature search revealed 77 eligible studies for inclusion. Different RCM features in a broad spectrum of ISD have been described. Further, RCM has been used for monitoring treatment and evolution of ISD, as well as for diagnostic purposes. This systematic review provides an overview of the broad spectrum of ISD imaged by RCM. Although RCM seems to be a promising monitoring and diagnostic tool for ISD, studies with appropriate methodological quality are necessary to create adequate guidelines and protocols for further implementation of RCM in clinical practice.

Reflectance confocal microscopy: non-invasive distinction between actinic keratosis and squamous cell carcinoma

Early recognition of squamous cell carcinoma (SCC) is difficult. Non‐invasive reflectance confocal microscopic (RCM) imaging of the skin is a promising diagnostic technique. Although several RCM features for SCC and AK have been described, it is not determined whether RCM has the ability to distinguish between SCC and actinic keratosis (AK).

Understanding the Acute Skin Injury Mechanism Caused by Player-Surface Contact During Soccer: A Survey and Systematic Review.

Background: Superficial skin injuries are considered minor, and their incidence is probably underestimated. Insight into the incidence and mechanism of acute skin injury can be helpful in developing suitable preventive measures and safer playing surfaces for soccer and other field sports. Purpose: To gain insight into the incidence and severity of skin injuries related to soccer and to describe the skin injury mechanism due to player-surface contact. Study Design: Systematic review; Level of evidence, 4. Methods: The prevention model by van Mechelen et al (1992) combined with the injury causation model of Bahr and Krosshaug (2005) were used as a framework for the survey to describe the skin injury incidence and mechanism caused by player-surface contact. Results: The reviewed literature showed that common injury reporting methods are mainly based on time lost from participation or the need for medical attention. Because skin abrasions seldom lead to absence or medical attention, they are often not reported. When reported, the incidence of abrasion/laceration injuries varies from 0.8 to 6.1 injuries per 1000 player-hours. Wound assessment techniques such as the Skin Damage Area and Severity Index can be a valuable tool to obtain a more accurate estimation of the incidence and severity of acute skin injuries. Conclusion: The use of protective equipment, a skin lubricant, or wet surface conditions has a positive effect on preventing abrasion-type injuries from artificial turf surfaces. The literature also shows that essential biomechanical information of the sliding event is lacking, such as how energy is transferred to the area of contact. From a clinical and histological perspective, there are strong indications that a sliding-induced skin lesion is caused by mechanical rather than thermal injury to the skin.

Establishing the dynamics of neutrophil accumulation in vivo by reflectance confocal microscopy

Reflectance confocal microscopy (RCM) is an imaging tool, which visualizes the epidermal skin layers in vivo with a cellular resolution. Neutrophil accumulation is a characteristic feature in psoriasis and is thought to play a role in the pathophysiology of psoriasis. Until now, imaging of neutrophil accumulation in vivo is not performed. We evaluated the dynamics of neutrophil migration in active psoriatic lesions by non‐invasive RCM imaging. Additionally, we evaluated the time phasing and duration of neutrophil trafficking. We performed RCM imaging prior to the start of topical treatment and for seven consecutive days with a 24‐h time interval at the Radboud University Medical Center, Nijmegen, the Netherlands. Twelve psoriatic lesions in three patients with a severe exacerbation of psoriasis were included. The four most active lesions were selected in each patient based on the highest degree of redness, induration and expansion in the previous 2 weeks. In all lesions, a cyclic pattern of neutrophil migration was observed, consisting of squirting papillae, transepidermal migration, accumulation in the stratum spinosum, accumulation in the stratum corneum and degeneration of the abscesses. The time interval of a neutrophil‐trafficking cycle was 5–7 days and showed a synchronic time phasing. This study is the first to establish the dynamics and time phasing of neutrophil migration in vivo in psoriatic lesions. Previously reported theories were confirmed by these novel in vivo data. RCM might distinguish between active or chronic psoriatic areas, which might contribute to new insights into the pathogenesis of psoriasis.

Combining tape stripping and non‐invasive reflectance confocal microscopy : an in vivo model to study skin damage

Evaluation of (immuno)histological and cell biological changes in damaged skin requires often an invasive skin biopsy, making in vivo models inappropriate to study skin damage. Reflectance confocal microscopy (RCM) might overcome this limitation. Therefore, we evaluated the use of a tape‐stripping model in combination with RCM to provide morphological data on skin damage and recovery.

Prospective differentiation of clinically difficult to distinguish nodular basal cell carcinomas and intradermal nevi by non‐invasive Reflectance Confocal Microscopy: a case series study

Clinical differentiation between a nodular basal cell carcinoma (nBCC) and a benign intradermal nevus can be difficult. Even with additional dermoscopic evaluation, a correct diagnosis may be difficult. Currently, histopathological examination of a biopsy is the gold standard to differentiate between these lesions. However, this is an invasive technique and sampling errors can occur. In vivo Reflectance Confocal Microscopy (RCM) is a non‐invasive technique to evaluate a skin lesion at a microscopic level. RCM features of nBCCs and intradermal nevi have been described in research setting. However, the use of RCM for prospective differentiation between difficult to diagnose nodules into nBCCs and intradermal nevi in clinical practice has not been demonstrated yet.

Measurement of skin surface biomakers by Transdermal Analyses Patch following different in vivo models of irritation: a pilot study

FibroTx Transdermal Analyses Patch (TAP) is a novel technology for non‐invasive measurements of protein biomarkers on the skin surface, in vivo. The aim of this study was to explore the potential of TAP in detecting skin surface biomarkers following mild perturbations, in vivo, using two experimental models: tape stripping, mimicking acute barrier disruption, and histamine iontophoresis, mimicking acute and local inflammation at minimal skin barrier insult.

The current role of in vivo reflectance confocal microscopy within the continuum of actinic keratosis and squamous cell carcinoma: a systematic review

BackgroundClinical differentiation between actinic keratosis (AK), squamous cell carcinoma (SCC) in situ, and invasiveSCCand its variants may be difficult. Reflectance confocal microscopy (RCM) is a noninvasive technique for in vivo skin imaging.ObjectivesTo explicate the diagnostic and monitoring use of RCM within the spectrum of AK and SCC, and evaluate the accuracy of RCM for these diagnoses relative to histopathology.Materials & methodsA systematic literature search was performed in PubMed, EMBASE, the Cochrane Library, and Web of Science databases. The quality was assessed using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist.ResultsTwenty-five eligible studies were included. Different diagnostic RCM features have been described for AK, actinic cheilitis (AC), erythroplasia of Queyrat, Bowen disease, invasive SCC, and keratoacanthoma (KA). The overall range of sensitivity and specificity of RCM for the diagnosis of SCC, AK, SCC in situ, and KA was 79-100% and 78-100%, respectively.ConclusionThe current literature describes the use ofRCMfor diagnosing AK,AC, erythroplasia of Queyrat, Bowen disease, invasive SCC, and KA, as well as for monitoring treatments of AK, with good accuracy. Unfortunately, studies with high method-ological quality are lacking. Pre-treatment of hyperkeratotic lesions and uniform definitions of RCM features are required to simplify the differentiation between AKs, SCC in situ, and SCC and its variants in clinical practice.

Application of leukotriene B4 and reflectance confocal microscopy as a noninvasive in vivo model to study the dynamics of skin inflammation

Application of leukotriene B4 (LTB4) is an established in vivo model that locally induces skin inflammation. Currently in this model, a biopsy is inevitable. In vivo reflectance confocal microscopy (RCM), a noninvasive imaging technique, could overcome this limitation. To find out to what extent RCM may be an in vivo investigative and diagnostic tool in neutrophilic conditions, we studied the dynamics of polymorphonuclear leukocytes (PMN) migration from dermis to stratum corneum using an established LTB4 model.