Vivo Reflectance Confocal Microscopy Research Articles

In Vivo reflectance confocal microscopy of cutaneous acute graft-versus-host disease: concordance with histopathology and interobserver reproducibility of a glossary with representative images.

The reliability to non-invasively identify features of inflammatory dermatoses by reflectance confocal microscopy (RCM) remains unknown. Lack of formal training among RCM readers can result in inconsistent assessments, limiting clinical utility. Specific consensus terminology with representative images is necessary to ensure consistent feature-level interpretation among RCM readers. (1) Develop a glossary with representative images of RCM features of cutaneous acute graft-versus-host disease (aGVHD) for consistent interpretation among observers, (2) assess the interobserver reproducibility among RCM readers using the glossary, and (3) determine the concordance between RCM and histopathology for aGVHD features. Through an iterative process of refinement and discussion among five international RCM experts, we developed a glossary with representative images of RCM features of aGVHD. From April to November 2018, patients suspected of aGVHD were imaged with RCM and subsequently biopsied. 17 lesions from 12 patients had clinically and pathologically confirmed cutaneous aGVHD. For each of these lesions, four dermatopathologists and four RCM readers independently evaluated the presence of aGVHD features in scanned histopathology slides and 1.5 × 1.5 mm RCM submosaics at 4 depths (blockstacks) respectively. RCM cases were adjudicated by a fifth RCM expert. Interobserver reproducibility was calculated by mean pairwise difference (U statistic). Concordance between modalities was determined by fraction of assignments with agreement. We present a glossary with representative images of 18 aGVHD features by RCM. The average interobserver reproducibility among RCM readers (75%, confidence interval, CI: 71-79%) did not differ significantly from dermatopathologists (80%, 76-85%). The concordance between RCM and histopathology was 59%. By using the glossary, the interobserver reproducibility among RCM readers was similar to the interobserver reproducibility among dermatopathologists. There was reasonable concordance between RCM and histopathology to visualize aGVHD features. The implementation of RCM can now be advanced in a variety of inflammatory conditions with a validated glossary and representative image set.

In Vivo Reflectance Confocal Microscopy as a Response Monitoring Tool for Actinic Keratoses Undergoing Cryotherapy and Photodynamic Therapy.

Simple SummaryThe assessment of actinic keratoses (AKs) in prevention and therapeutic trials, as well as clinical practice, could significantly benefit from the incorporation of non-invasive imaging technology. Such technology has the potential to enhance the objective evaluation of clinical and subclinical AKs with the added advantage of sequential monitoring. In vivo reflectance confocal microscopy (RCM) allows for the non-invasive imaging of AKs at a cellular level. We aimed to establish an in in vivo RCM protocol for AK response monitoring, ultimately leading to more reliable characterization of longitudinal responses and therapy optimization.Reflectance confocal microscopy (RCM) presents a non-invasive method to image actinic keratosis (AK) at a cellular level. However, RCM criteria for AK response monitoring vary across studies and a universal, standardized approach is lacking. We aimed to identify reliable AK response criteria and to compare the clinical and RCM evaluation of responses across AK severity grades. Twenty patients were included and randomized to receive either cryotherapy (n = 10) or PDT (n = 10). Clinical assessment and RCM evaluation of 12 criteria were performed in AK lesions and photodamaged skin at baseline, 3 and 6 months. We identified the RCM criteria that reliably characterize AK at baseline and display significant reduction following treatment. Those with the highest baseline odds ratio (OR), good interobserver agreement, and most significant change over time were atypical honeycomb pattern (OR: 12.7, CI: 5.7–28.1), hyperkeratosis (OR: 13.6, CI: 5.3–34.9), stratum corneum disruption (OR: 7.8, CI: 3.5–17.3), and disarranged epidermal pattern (OR: 6.5, CI: 2.9–14.8). Clinical evaluation demonstrated a significant treatment response without relapse. However, in grade 2 AK, 10/12 RCM parameters increased from 3 to 6 months, which suggested early subclinical recurrence detection by RCM. Incorporating standardized RCM protocols for the assessment of AK may enable a more meaningful comparison across clinical trials, while allowing for the early detection of relapses and evaluation of biological responses to therapy over time.

A Systematic Review and Meta-Analysis of the Accuracy of in VivoReflectance 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’ 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, 0.87–0.95; I2 = 85.27%) and 0.93 (95% CI, 0.85–0.97; I2 = 94.61%), the pooled positive and negative likelihood ratios were 13.51 (95% CI, 5.8–31.37; I2 = 91.01%) and 0.08 (95% CI, 0.05–0.14; I2 = 84.83%), and the pooled diagnostic odds ratio was 160.31 (95% CI, 64.73–397.02; 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.

In Vivo Reflectance Confocal Microscopy for the Diagnosis of Melanoma and Melanotic Macules of the Lip

ImportanceBenign melanotic macules (MAC) are the most frequent cause of lip pigmentation and sometimes difficult to differentiate from lip melanoma (MEL).ObjectivesTo report in vivo reflectance confocal microscopy (RCM) features of normal lips of different phototypes and to identify features that assist in distinguishing MEL from MAC using dermoscopy and RCM.Design, Setting, and ParticipantsFor this retrospective observational study, 2 groups of patients from 2 tertiary referral centers for melanoma (Sydney Melanoma Diagnostic Centre and Melanoma Institute Australia) were recruited between June 2007 and January 2015. Group 1 included patients with normal lips and different phototypes, and Group 2 consisted of patients with MAC and MEL; RCM and dermoscopy were used for lips analysis.Main Outcomes and MeasuresOverall, 92 RCM features were correlated with clinical history, dermoscopic images, and histopathology in all patients with MEL and 5 patients with MAC.ResultsImages from the vermillion and/or mucosal part of the lip were recorded from 10 patients with clinically normal lips (mean [SD] age, 34.5 [6.1] years), 16 patients with MAC (mean [SD] age, 49.6 [17.9] years), and 5 patients with 6 cases of MEL (1 patient had a recurrent lesion; mean [SD] age, 56.2 [15.5] years). In normal lips, the draped pattern—a previously described MAC RCM feature—was identified in all cases. In MEL, the following findings were frequent and significantly different from MAC: epidermal disarray; pagetoid infiltration of dendritic and/or round cells; a nonspecific architectural pattern at the dermoepidermal junction (DEJ); nonhomogenously distributed papillae; continuous (lentiginous) proliferation of cells with marked atypia at the DEJ, especially in interpapillary spaces; a higher number of dendritic cells (especially roundish); and atypical round cells at the DEJ. The cellular body area of dendritic cells was about the double in MEL compared with MAC. An RCM lip algorithm was developed that provided 100% sensitivity and 88% specificity for the diagnosis of MEL of the vermillion and mucosal part of the lip. With dermoscopy, MAC were correctly classified as benign in 13 of 16 cases (81%) and MEL were classified as equivocal or malignant in 5 of 6 cases (83%).Conclusions and RelevanceReflectance confocal microscopy can assist in the differential diagnosis of lip MEL and MAC. An RCM Lip Score that we developed based on study results is proposed and needs to be validated on an independent data set.

An Evolving Approach to the Detection of Melanoma and Other Skin Cancers Using In Vivo Reflectance Confocal Microscopy

An Evolving Approach to the Detection of Melanoma and Other Skin Cancers Using In Vivo Reflectance Confocal Microscopy

In Vivo Reflectance Confocal Microscopy of Basal Cell Carcinoma: Feasibility of Preoperative Mapping of Cancer Margins

Reflectance confocal microscopy (RCM) images skin at cellular resolution and has shown utility for the diagnosis of nonmelanoma skin cancer in vivo. It has the potential to define lesion margins before surgical therapy.ObjectivesTo investigate the feasibility of RCM in defining the margins of basal cell carcinoma before surgery.MethodsThe margins of 10 lesions were evaluated using RCM. Biopsies of the margins were used to confirm the results. A protocol was constructed to define margins. RCM was used to delineate preoperative surgical margins in 13 patients. Intraoperative frozen biopsy was used to confirm the margins.ResultsIn seven of 10 (70.0%) cases, the margins of the cancer were identified suing RCM. The tumor island was the critical feature in identifying the margins. In 12 of 13 (92.3%) cases, frozen biopsy corroborated that the surgical margins delineated by RCM were clear.ConclusionRCM imaging of the margins is feasible and demonstrates the possibility of preoperative mapping of cancer margins.

Correlation of Dermoscopy With In Vivo Reflectance Confocal Microscopy of Streaks in Melanocytic Lesions

To analyze dermoscopically identified streaks by direct correlation with features visualized on reflectance confocal microscopy (RCM). We evaluated by RCM melanocytic lesions showing peripheral streaks on dermoscopy. A digital camera connected to the RCM computer enabled direct analysis of the streaks. The lesions were excised and histopathologically analyzed. Dermatology clinic specializing in pigmented lesions. The study population comprised 7 patients with melanocytic lesions, including 2 melanomas, 4 dysplastic nevi, and 1 compound nevus with spitzoid features. In 6 of the cases, peripheral streaks were visualized on RCM as confluent aggregates composed of bright, ill-demarcated cells. These aggregates were contiguous with the bright central part of the lesion and appeared to be curving around dermal papillae. Of the 6 lesions, 3 with elongated aggregates visualized on RCM harbored peripheral, elongated nests on histopathologic examination, and 2 with shorter, more ill-defined peripheral aggregates visualized on RCM had smaller, more poorly formed peripheral nests on histopathologic examination. The seventh lesion showed few peripheral streaks on dermoscopy; however, corresponding features visualized on RCM showed discrete, dense, round nests aligned in proximity. We did not recognize in the present series distinguishing characteristics on RCM that could differentiate between the peripheral streaks of malignant melanoma and nevi. Direct dermoscopy-RCM correlation is a feasible method to study streaks and may help to improve the classification methods used in dermoscopy. Additional studies with larger series are needed to confirm our findings and may help elucidate the morphologic and biological nature of peripheral streaks.

Detection of UV-Induced Pigmentary and Epidermal Changes Over Time Using In Vivo Reflectance Confocal Microscopy

In vivo reflectance confocal microscopy (RCM) provides high-resolution optical sections of the skin in its native state, without needing to fix or section the tissue. Melanin provides an excellent contrast for RCM, giving a bright signal in the confocal images. The pigmented guinea-pig is a common animal model to study human pigment induction and modulation, as its tanning response is comparable to human tanning after exposure to ultraviolet radiation (UVR). We investigated the applicability of RCM to detecting UVR-induced pigmentary changes in this model. Animals were exposed to solar simulator radiation for 7 days. RCM was performed during the irradiation and follow-up period. Compared to non-irradiated skin, an increase in melanocyte size, dendricity, and number, as well as increased pigment in keratinocytes, was seen in the irradiated epidermis. Interestingly, these changes could be detected even before a tanning response was clinically visible. UVR-induced epidermal hyperplasia could also be detected and quantified. In conclusion, in vivo RCM is a sensitive non-invasive imaging technique that can repeatedly measure epidermal pigmentation and thickness, as demonstrated in the guinea-pig model. This technique should greatly enhance our appreciation of dynamic pigmentary changes in human or animal skin over time and in response to specific stimuli.