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. 2025 May 22;17(11):1745.
doi: 10.3390/cancers17111745.

Where Reflectance Confocal Microscopy Provides the Greatest Benefit for Diagnosing Skin Cancers: The Experience of the National Cancer Institute of Naples

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Where Reflectance Confocal Microscopy Provides the Greatest Benefit for Diagnosing Skin Cancers: The Experience of the National Cancer Institute of Naples

Marco Palla et al. Cancers (Basel). .

Abstract

Background: Although complete excision of suspicious melanocytic lesions is mandatory, it carries the risk of unnecessary scarring on one hand and inadequate treatment of misdiagnosed lesions on the other. Objectives: We evaluated the sensitivity, specificity, and predictive value of reflectance confocal microscopy (RCM) in diagnosing pigmented lesions with clinically ambiguous features-the so-called "gray zone" -and compared its performance with the more established technique of epiluminescence microscopy (ELM). Results: Between 2019 and 2020, a total of 2282 melanocytic lesions were assessed using both ELM and RCM. Histopathological diagnosis aligned with the ELM risk classification in 91.6% of melanocytic lesions, specifically in 92.0% of very-high-risk lesions, 88.5% of high-risk lesions, 66.3% of medium-risk lesions, 96.3% of low-risk lesions, and 98.0% of very low-risk lesions. Similarly, histopathological diagnosis of these lesions corresponded with the RCM risk assessment in 91.2% of cases, including 90.9% of very-high-risk lesions, 84.4% of high-risk lesions, 93.1% of medium-risk lesions, 90.5% of low-risk lesions, and 96.2% of very low-risk lesions. Conclusions: Although ELM is a valuable tool for increasing the efficacy of clinical diagnosis, its reliability decreases for a group of lesions that appear suspicious during clinical skin examination. RCM, as a newer technique, appears to improve malignancy detection in suspicious melanocytic lesions without requiring excision; its sensitivity and specificity remain high even in lesions classified by ELM as posing a medium risk of malignancy.

Keywords: epiluminescence microscopy; melanocytic lesions; melanoma; reflectance confocal microscopy.

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Conflict of interest statement

All the authors declare no competing interests except for P.A.A. He has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp and Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, iTeos, Medicenna, Bio-Al Health, ValoTX, and Replimmune. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer, and Sanofi, as well as travel support from Pfizer. The funders of this study had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Some examples of clinical (columns a,b), RCM (columns c,d), and histological (column e) images of type-3 pigmented lesions. Columns a,b show clinical and dermoscopic (ELM) images, respectively. Dermoscopic images highlight key features used for risk stratification, such as pigment network irregularities, asymmetry in color or structure, and the presence of melanoma-associated patterns including pseudopods, radial streaming, and blue-gray veil. Column c presents RCM images at the dermoepidermal junction, where architectural disarray, presence of atypical bright cells, and irregular nests are assessed. Column d shows magnified areas of interest; red arrows correspond to the same locations of the cross-sectional images in column e. The red rectangle indicates areas where melanoma-specific confocal features are present, including disarray of the dermoepidermal junction and atypical dendritic or round cells. Column e shows corresponding histopathological images used as reference standards. Rows 1, 2, 4, and 5: dysplastic nevus; rows 3 and 6: in situ melanoma on nevus.
Figure 2
Figure 2
ROC curves showing specificity and sensitivity of ELM and RCM. Red line: Random reference line.

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