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Competing Interests: Conflicts of interest None disclosed.

Background: There is lack of uniformity in the reflectance confocal microscopy (RCM) terminology for melanocytic lesions., Objective: To review published RCM terms for melanocytic lesions and identify redundant, synonymous terms., Methods: A systematic review of original research articles adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was conducted until August 15, 2018. Two investigators gathered all published RCM terms used to describe melanoma and melanocytic nevi. Synonymous terms were grouped based on similarity in definition and in histopathologic correlation., Results: Out of 156 full-text screened articles, 59 studies met the inclusion criteria. We identified 209 terms; 191 (91.4%) corresponding to high-magnification/cellular-level terms and 18 (8.6%) corresponding to low-magnification/architectural patterns terms. The overall average use frequency of RCM terms was 3.1 times (range, 1-31). By grouping of individual RCM terms based on likely synonymous definitions and by eliminating terms lacking clear definition, the total number of RCM terms could be potentially reduced from 209 to 40 terms (80.8% reduction)., Limitations: Non-English and non-peer-reviewed articles were excluded., Conclusions: This systematic review of published RCM terms identified significant terminology redundancy. It provides the basis for subsequent terminology consensus on melanocytic neoplasms., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Accurate basal cell carcinoma (BCC) subtyping is requisite for appropriate management, but non-representative sampling occurs in 18% to 25% of biopsies. By enabling non-invasive diagnosis and more comprehensive sampling, integrated reflectance confocal microscopy-optical coherence tomography (RCM-OCT) may improve the accuracy of BCC subtyping and subsequent management. We evaluated RCM-OCT images and histopathology slides for the presence of two key features, angulation and small nests and cords, and calculated (a) sensitivity and specificity of these features, combined and individually, for identifying an infiltrative BCC subtype and (b) agreement across modalities., Methods: Thirty-three RCM-OCT-imaged, histopathologically-proven BCCs (17 superficial and/or nodular; 16 containing an infiltrative component) were evaluated., Results: The presence of angulation or small nests and cords was sufficient to identify infiltrative BCC on RCM-OCT with 100% sensitivity and 82% specificity, similar to histopathology (100% sensitivity, 88% specificity, kappa = 0.82). When both features were present, the sensitivity for identifying infiltrative BCC was 100% using either modality and specificity was 88% on RCM-OCT vs 94% on histopathology, indicating near-perfect agreement between non-invasive and invasive diagnostic modalities (kappa = 0.94)., Conclusions: RCM-OCT can non-invasively identify key histopathologic features of infiltrative BCC offering a possible alternative to traditional invasive biopsy., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Determining whether repigmentation within or adjacent to lentigo maligna or lentigo maligna melanoma (LM/LMM) scars represents recurrence of melanoma is challenging. The use of reflectance confocal microscopy (RCM) and dermoscopy may aid in differentiating true melanoma recurrence from other causes of repigmentation., Objectives: To describe the characteristics of repigmentation within or adjacent to LM/LMM scars observable on RCM and dermoscopy., Methods: We retrospectively analysed patients who presented with new pigmentation within or adjacent to scars from surgically treated LM/LMM between January 2014 and December 2018. Clinical and demographic characteristics and time to recurrence were recorded. RCM was used to evaluate areas of pigmentation before biopsy. If available, dermoscopic images were also evaluated., Results: In total, 30 confocal studies in 29 patients were included in the study cohort. Twenty-one patients had biopsy-confirmed recurrent LM/LMM; the remainder had pigmented actinic keratosis (n = 4) or hyperpigmentation/solar lentigo (n = 5). RCM had sensitivity of 95.24% (95% CI, 76.18-99.88%), specificity of 77.7% (95% CI, 39.99-97.19%), positive predictive value of 90.91% (95% CI, 74.58-97.15%) and negative predictive value of 87.5% (95% CI, 50.04-98.0%). The most common dermoscopic feature observed among patients with recurrent LM/LMM was focal homogeneous or structureless areas of light-brown pigmentation (92.8% vs. 37.5% in patients with other diagnoses; P = 0.009). LM-specific dermoscopic criteria were present in only 28.5% of patients with recurrent LM/LMM., Conclusions: Reflectance confocal microscopy and dermoscopy are valuable tools for the comprehensive evaluation of repigmentation within or adjacent to LM scars., (© 2019 European Academy of Dermatology and Venereology.)

Background: Diagnostic accuracy of reflectance confocal microscopy (RCM) as a stand-alone diagnostic tool for suspect skin lesions has not been extensively studied., Objective: Primary aim was to measure experts' accuracy in RCM-based management decisions. Secondary aim was to identify melanoma-specific RCM features., Methods: The study enrolled patients ≥18 years that underwent biopsy of skin lesions clinically suspected to be melanoma. One hundred lesions imaged by RCM were randomly selected from 439 lesions prospectively collected at four pigmented lesion clinics. The study data set included 23 melanomas, three basal cell and two squamous cell carcinomas, 11 indeterminate melanocytic lesions and 61 benign lesions including 50 nevi. Three expert RCM evaluators were blinded to clinical or dermoscopic images, and to the final histopathological diagnosis. Evaluators independently issued a binary RCM-based management decision, 'biopsy' vs. 'observation'; these decisions were scored against histopathological diagnosis, with 'biopsy' as the correct management decision for malignant and indeterminate lesions. A subset analysis of 23 melanomas and 50 nevi with unequivocal histopathological diagnosis was performed to identify melanoma-specific RCM features., Results: Sensitivity, specificity and diagnostic accuracy were 74%, 67% and 70% for reader 1, 46%, 84% and 69% for reader 2, and 72%, 46% and 56% for reader 3, respectively. The overall kappa for management decisions was 0.34. Readers had unanimous agreement on management for 50 of the 100 lesions. Non-specific architecture, non-visible papillae, streaming of nuclei, coarse collagen fibres and abnormal vasculature showed a significant association with melanoma in the evaluation of at least two readers., Conclusions: Reflectance confocal microscopy tele-consultation of especially challenging lesions, based on image review without benefit of clinical or dermoscopy images, may be associated with limited diagnostic accuracy and interobserver agreement. Architectural and stromal criteria may emerge as potentially useful and reproducible criteria for melanoma diagnosis., (© 2018 European Academy of Dermatology and Venereology.)

The classification of melanoma into four histological subtypes has been questioned regarding its clinical validity in providing relevant information for treatment for metastatic tumors. Specific genetic alterations are associated with particular clinical and histopathological features, suggesting that these could be helpful in refining existing melanoma classification schemes. We analyzed BRAF V600E mutated melanomas to explore the Reflectance confocal microscopy (RCM) utility as a screening aid in the evaluation of the most appropriate patients for genetic testing. Thus, 32 melanomas were assessed regarding their BRAF V600E mutational status. Experts blinded to dermoscopic images and V600E immunohistochemistry results evaluated RCM images regarding previously described melanoma features. BRAF positive melanomas were related to younger age (p = 0.035), invasive melanomas (p = 0.03) and to the presence of hiporreflective cells (p = 0.02), epidermal nests (p = 0.02), dermal-epidermal junction nests (p = 0.05), edged papillae (p = 0.05), and bright dots (p = 0.05), and to absence of junctional thickening due to isolated cells (p = 0.01) and meshwork (p = 0.02). This study can not characterize other mutations in the BRAF, because the immunohistochemistry is specific to the type V600E. The findings should encourage the genetic evaluation of BRAF mutation. This study highlights the potential of RCM as a supplementary tool in the screening of BRAF-mutated melanomas.

Importance: Reflectance confocal microscopy (RCM) studies have been performed to identify criteria for diagnosis of skin neoplasms. However, RCM-based diagnosis is operator dependent. Hence, reproducibility of RCM criteria needs to be tested., Objective: To test interobserver reproducibility of recognition of previously published RCM descriptors and accuracy of RCM-based skin cancer diagnosis., Design, Setting, and Participants: Observational retrospective web-based study of a set of RCM images collected at a tertiary academic medical center. Nine dermatologists (6 of whom had ≥3 years of RCM experience) from 6 countries evaluated an RCM study set from 100 biopsy-proven lesions, including 55 melanocytic nevi, 20 melanomas, 15 basal cell carcinomas, 7 solar lentigines or seborrheic keratoses, and 3 actinic keratoses. Between June 15, 2010, and October 21, 2010, participanting dermatologists, blinded to histopathological diagnosis, evaluated 3 RCM mosaic images per lesion for the presence of predefined RCM descriptors., Main Outcomes and Measures: The main outcome was identification of RCM descriptors with fair to good interrater agreement (κ statistic, ≥0.3) and independent correlation with malignant vs benign diagnosis on discriminant analysis. Additional measures included sensitivity and specificity for diagnosis of malignant vs benign for each evaluator, for majority diagnosis (rendered by ≥5 of 9 evaluators), and for experienced vs recent RCM users., Results: Eight RCM descriptors showed fair to good reproducibility and were independently associated with a specific diagnosis. Of these, the presence of pagetoid cells, atypical cells at the dermal-epidermal junction, and irregular epidermal architecture were associated with melanoma. Aspecific junctional pattern, basaloid cords, and ulceration were associated with basal cell carcinomas. Ringed junctional pattern and dermal nests were associated with nevi. The mean sensitivity for the group of evaluators was 88.9% (range, 82.9%-100%), and the mean specificity was 79.3% (range, 69.2%-90.8%). Majority diagnosis showed sensitivity of 100% and specificity of 80.0%. Sensitivity was higher for experienced vs recent RCM users (91.0% vs. 84.8%), but specificity was similar (80.0% vs. 77.9%)., Conclusions and Relevance: The study highlights key RCM diagnostic criteria for melanoma and basal cell carcinoma that are reproducibly recognized among RCM users. Diagnostic accuracy increases with experience. The higher accuracy of majority diagnosis suggests that there is intrinsically more diagnostic information in RCM images than is currently used by individual evaluators.

Dermatophytoses are common skin infections. Traditional diagnostic tests such as skin scrapings for light microscopy examination, fungal cultures and biopsies remain imperfect due to false-negative test results, cost, time required to perform the procedure, time delays in test results and/or a requirement for an invasive procedure. Herein, we present a case of an 80-year-old female whose tinea incognito was non-invasively diagnosed within seconds using handheld reflectance confocal microscopy (RCM). As non-invasive skin imaging continues to improve, we expect light-based office microscopy to be replaced with technologies such as RCM, which has multiple and continually expanding diagnostic applications., (© 2015 Blackwell Verlag GmbH.)

Background: Lichen planus-like keratosis (LPLK) may be difficult to differentiate from melanoma and other skin cancers on sun-damaged skin based on clinical and dermoscopic examination. Reflectance confocal microscopy (RCM) allows evaluation of skin lesions at high resolution., Objectives: The aim of this study was to identify criteria for specific diagnosis of LPLK using in vivo RCM., Methods: Lesions included in the study were derived from patients presenting for skin examination at a private dermatology practice specializing in skin cancer. We retrospectively analysed RCM features of 28 biopsy-proven LPLK and compared them to RCM findings in skin cancers on sun-damaged skin, including five in situ squamous cell carcinomas, six actinic keratoses, seven superficial basal cell carcinomas and eight melanomas., Results: The main RCM features of LPLK and their relative frequencies were: (i) typical honeycomb pattern of the spinous layer (78.6%); (ii) elongated cords and/or bulbous projections at the dermal-epidermal junction (75%); and (iii) numerous plump-bright cells and/or bright stellate spots in the superficial dermis (92.9%). These RCM features correlated with the following histopathological findings respectively: (i) spinous-granular layers without significant atypia of keratinocytes; (ii) elongated, bulbous rete ridges; and (iii) dense infiltration of melanophages and lymphocytes in superficial dermis. We propose diagnostic criteria that classify correctly 71.4% of LPLK, while avoiding misclassification of any of the skin cancers in the present series as LPLK., Conclusions: We identified RCM criteria for diagnosis of LPLK that correlate well with histopathological findings and that allow differentiation of LPLK from skin cancer., (© 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.)

Background: Intraepidermal Langerhans cells (ILC) are difficult to differentiate from melanocytes under reflectance confocal microscopy (RCM) and their presence may simulate pagetoid spread of melanocytes on RCM images., Objective: We sought to correlate bright round and dendritic cells in a pagetoid pattern identified on RCM with findings of conventional histopathology and immunohistochemistry for lesions that were falsely diagnosed as melanoma by RCM., Methods: This retrospective study included histopathologically proven nevi, imaged by RCM, which displayed bright cells in a pagetoid pattern (BCPP) under RCM, resulting in the incorrect RCM diagnosis of melanoma. Morphological comparisons were made between RCM images of nevi showing BCPP, histopathologically proven melanomas displaying BCPP, and biopsy-proven nevi without BCPP., Results: We identified 24 nevi that were falsely diagnosed as melanoma by RCM because of the presence of BCPP. These pagetoid cells on RCM corresponded on histopathology to ILC with a high density in 23 of the 24 nevi (95%) and to melanocytes in 7 of the 24 nevi (29%). Among 6 melanomas displaying BCPP on RCM, ILC with high density were observed histopathologically in 5 of the 6 cases (83%) and pagetoid melanocytes were seen in all 6 cases (100%)., Limitations: The results cannot be generalized to clinically banal-appearing nevi., Conclusions: Although the finding of BCPP is a useful RCM feature for the diagnosis of melanoma, it does not always imply the presence of pagetoid melanocytes but may at times represent ILC., (Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Solitary pink lesions often manifest nondescript clinical and dermatoscopic primary morphologic features. The differential diagnosis for pink lesions tends, therefore, to be broad, ranging from inflammatory processes to malignancy. In vivo reflectance confocal microscopy (RCM) may help in the evaluation of pink lesions., Objective: We sought to demonstrate the use of RCM as an adjunct to the bedside diagnosis of pink lesions., Methods: We describe a series of patients with clinically and dermatoscopically equivocal pink lesions for which RCM examination allowed for a rapid and accurate diagnosis. All lesions were excised for histopathologic evaluation. Integrating the findings in the case series with a literature review, we present RCM diagnostic criteria for pink lesions., Results: Lesions included basal cell carcinoma, squamous cell carcinoma, amelanotic melanoma, and inflamed seborrheic keratosis. RCM shows distinctive findings for each diagnostic entity when stratified by anatomic level into suprabasal epidermis, dermoepidermal junction, and papillary dermis. In the cases presented RCM allowed for a rapid and accurate noninvasive diagnosis., Limitations: The study is descriptive and does not test accuracy of RCM criteria in a prospective series of pink lesions., Conclusion: RCM may add useful diagnostic features to the clinical evaluation of solitary pink lesions.

Background: Clear cell acanthoma (CCA) is a rare, benign neoplasm of unknown etiology, whose dermoscopic and histological features have been previously described. Usually, CCA can be diagnosed by clinical and dermoscopic examination. In some cases, diagnosis remains uncertain, and histological examination is needed. The aim of this paper was to describe the features of reflectance confocal microscopy (RCM) in diagnosing CCA, compare them with findings on dermoscopy and histology, and evaluate their possible usefulness in CCA evaluation., Patients and Methods: Five lesions diagnosed clinically as CCA were imaged using dermoscopy and RCM. All lesions were surgically excised to confirm the diagnosis and compare the morphological attributes under light microscopy with in vivo imaging., Results: RCM showed well-circumscribed lesions, often edged by a hyperkeratotic collarette with parakeratosis; inflammatory cells in the spinous layer; large keratinocytes; acanthosis with papillomatosis; epidermal disarray; and dilated capillaries forming glomeruloid shapes in the upper dermis., Conclusions: In this small study, RCM was able to identify most of the established diagnostic histological features of CCA. RCM appears to be a useful tool for in vivo diagnosis of CCA and may help avoid unnecessary biopsies.

Background: Reflectance confocal microscopy (RCM) has been used for over 10 years for in vivo skin imaging. However, to date no standard RCM terminology has been published., Objective: To establish a glossary of terms for RCM evaluation of melanocytic lesions., Methods: Prominent RCM researchers were presented with RCM images of melanocytic lesions. Reviewers evaluated RCM images for image quality, lesion architecture, and cellular details. Reviewers could utilize published descriptors or contribute unpublished terminology to describe lesion attributes. An online meeting was conducted to reach consensus that integrates and defines existing and new RCM descriptive terms., Results: We present a glossary with descriptors of image quality, normal skin morphology, lesion architecture, and cellular details for RCM evaluation of melanocytic lesions., Limitations: Usefulness of the glossary in RCM diagnosis of melanocytic lesions needs to be assessed., Conclusion: Standardization of terminology is important toward implementation of RCM in the clinical setting.

Objective: To analyze dermoscopically identified streaks by direct correlation with features visualized on reflectance confocal microscopy (RCM)., Design: 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., Setting: Dermatology clinic specializing in pigmented lesions., Patients: The study population comprised 7 patients with melanocytic lesions, including 2 melanomas, 4 dysplastic nevi, and 1 compound nevus with spitzoid features., Results: 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., Conclusions: 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.

Objective: To determine the utility of reflectance confocal microscopy (RCM) in the in vivo evaluation of dermoscopic structures of melanocytic lesions., Design: For each described dermoscopic feature, we evaluated by RCM at least 2 melanocytic lesions. A digital camera connected to the confocal computer enabled direct analysis of the dermoscopic structures. To ascertain precision of correlation, the orientation of the dermoscopic and RCM images were compared using a superimposed grid., Setting: Dermatology clinic specializing in pigmented lesions. Patients Eleven patients with melanocytic lesions, including 2 melanomas, 1 Spitz nevus, 7 dysplastic nevi, and 1 compound nevus. Main Outcome Measure Direct correlation of structures seen using dermoscopy with those seen using RCM., Results: There was a good correlation between the global dermoscopic pattern and findings on the 4 x 4-mm mosaic of confocal images at the level of the dermoepidermal junction. The atypical network correlated with variability in the size and shape of dermal papillae. Globules corresponded with aggregates of bright cells, and darker shades of brown on dermoscopy appeared brighter on RCM. In peripheral streaks, RCM showed dense aggregates of pleomorphic cells of variable brightness and ill-defined cellular borders. These aggregates were continuous with the bright mesh that composed the central bulk of the lesion. A blue-white veil correlated with disruption of the rimmed papillae meshlike pattern and sometimes with the presence of bright cells corresponding to melanophages., Conclusion: Correlating dermoscopic structures to RCM features is possible and a necessary step toward understanding the potential benefits of RCM in the clinical setting.

Background: Trichoepitheliomas (TE) are benign neoplasms of follicular differentiation. Solitary lesions are often confused with basal cell carcinoma (BCC). Reflectance confocal microscopy (RCM) and dermoscopy are imaging tools for in vivo, noninvasive evaluation of skin lesions. To date, there has been no description of their findings in the evaluation of TE., Objective: Our aim is to describe the dermoscopic and RCM findings of histopathologically confirmed TE., Methods: Four TE were evaluated, 2 each of the desmoplastic and nondesmoplastic variants. RCM was performed on 1 of the desmoplastic and both of the nondesmoplastic lesions., Results: Dermoscopically, all of the lesions showed arborizing telangiectasias. The desmoplastic lesions also had an ivory-white background throughout. RCM showed oval, darker-appearing tumor islands that contained brightly refractile material, consistent with keratin horn cysts at the center, as well as parallel bundles of highly refractile dermal collagen surrounding the tumor islands., Conclusion: The ivory-white background throughout the lesion seen on dermoscopy may be helpful in distinguishing desmoplastic TE from BCC. The RCM findings in TE of keratin-filled cysts in tumor islands and attachment of the tumor to follicular structures have not been previously observed in BCC, and thus may also be diagnostically helpful. Further study is necessary for validation of these findings., (2007 S. Karger AG, Basel)

Objective: To determine the utility of confocal scanning laser microscopy (CSLM) in the in vivo evaluation of congenital melanocytic nevi (CMNs) that are suggestive of having developed melanoma., Design: The CMNs suggestive of melanoma by clinical and dermoscopic examination were imaged by CSLM, and the findings correlated with the features seen on dermoscopic and histologic examination., Setting: Dermatology clinic specializing in pigmented lesions., Patients: Seven patients with clinically irregular small to medium CMNs., Interventions: The areas imaged by CSLM were sampled with 3-mm punch biopsy specimens. The entire lesion was subsequently excised. The punch biopsy specimens were step sectioned horizontally to correlate with the CSLM images. Excised samples were step sectioned and processed routinely. Histologic features observed on CSLM were correlated with the features seen on dermoscopic and light microscopic examination., Main Outcome Measure: Correlation of the structures seen using CSLM with the dermoscopic and histologic features of CMNs and melanoma., Results: The CSLM illustrated histologic characteristics of CMNs, including the presence of hyperpigmented keratinocytes, nevus cells, melanophages, and a normal "honeycomb" epidermal architecture. Features suggestive of melanoma were not evident by CSLM in 6 histologically proven benign CMNs. Histologic features associated with melanoma, such as an increased number of intraepidermal atypical melanocytes (pagetoid) and loss of normal epidermal cellular architecture, were identified by CSLM in 1 lesion, which on histologic analysis revealed melanoma in association with a CMN., Conclusion: Our results illustrate that CSLM may be useful for clinicopathologic correlations and for the preliminary noninvasive diagnosis of pigmented neoplasms in vivo.