Summary: Background: Differentiating Spitz naevi from melanomas can be difficult both clinically and dermoscopically. Previous studies have reported the potential role of in vivo reflectance confocal microscopy (RCM) in increasing diagnostic accuracy. Objectives: To define RCM criteria that can differentiate 'false twins', namely Spitz naevi and melanomas sharing similar dermoscopic appearance. Methods: Lesions histopathologically diagnosed as Spitz naevi or melanomas were retrospectively retrieved. They were selected to cover all dermoscopic types and were put into couples sharing similar aspects. Lesions were classified into three main dermoscopic categories: globular and starburst pattern, spitzoid with dotted vessels, and multicomponent or aspecific pattern. Results: RCM findings revealed that striking cell pleomorphism within the epidermis, widespread atypical cells at the dermoepidermal junction and marked pleomorphism within nests were significantly associated with the diagnosis of melanoma, while spindled cells and peripheral clefting were found exclusively with and pathognomonic of Spitz naevi. Furthermore, the analysis of a dermoscopic subgroup highlights the importance of striking pleomorphism and spindled cells as clues to differentiate 'false twins' with globular or starburst patterns. Conclusions: The current study highlights the role of RCM in discriminating 'false twins' of Spitz naevi and melanomas for lesions showing starburst and globular patterns on dermoscopy, whereas RCM is not useful in the other dermoscopic subgroups. What's already known about this topic? The differential diagnosis between Spitz naevi and melanomas can be challenging. Reflectance confocal microscopy (RCM) represents an add-on tool that improves diagnostic accuracy for skin cancer. What does this study add? RCM is useful to discriminate Spitz naevi and melanomas sharing the same dermoscopic pattern, namely globular or starburst patterns. RCM is not helpful in other dermoscopic subgroups.
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