Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2025;15(3):5961 1 Reflectance Confocal Microscopy and LC-OCT for Noninvasive Evaluation of Clonal Seborrheic Keratosis in Dark Skin Individuals Giulio Cortonesi1, Vittoria Cioppa1, Linda Tognetti1, Pietro Rubegni1, Elisa Cinotti1 1 Dermatology Section, Department of Medical, Surgical, and Neurological Sciences, Santa Maria Alle Scotte Hospital, Siena, Italy Citation: Cortonesi G, Cioppa V, Tognetti L, et al. Reflectance Confocal Microscopy and LC-OCT for Noninvasive Evaluation of Clonal Seborrheic Keratosis in Dark Skin Individuals. Dermatol Pract Concept. 2025;15(3):5961. DOI: https://doi.org/10.5826/dpc.1503a5961 Accepted: April 9, 2025; Published: July 2025 Copyright: ©2025 Cortonesi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Vittoria Cioppa, MD, Dermatology Section, Santa Maria alle Scotte Hospital, Viale Mario Bracci, 53100, Siena, Italy. E-mail: v.cioppa@student.unisi.it Orcid n.: 0000-0003-0640-2134 Introduction Line-field confocal optical coherence tomography (LC-OCT) is an advanced, non-invasive imaging modality that combines the principles of optical coherence tomogra- phy (OCT) with reflectance confocal microscopy (RCM) to provide high-resolution images of the skin at both the epi- dermal and superficial dermal levels. This technique enables real-time visualization of cellular and architectural details, al- lowing for improved diagnostic accuracy in various dermato- logical conditions [1-3]. LC-OCT has been widely applied for the non-invasive diagnosis of infectious, inflammatory, and neoplastic skin diseases, including cutaneous larva migrans, scabies, genital warts, and hypomelanotic melanoma [4]. Among the numerous cutaneous lesions evaluated with LC- OCT, seborrheic keratoses (SKs) represent a common benign epidermal tumor with various histopathological subtypes, including the clonal variant. Clonal seborrheic keratoses (CSKs) are characterized histologically by intraepidermal nests of basaloid or squamous cells and may exhibit features overlapping with other pigmented lesions, such as clear cell acanthoma and melanoma [5]. Case Presentation A black patient presented to our dermatology clinic for the appearance of a rapidly growing nodular skin lesion on the thigh (Figure 1 A). The growth was interpreted as a nodular melanoma by the general practitioner. On clini- cal examination, the growth appeared nodular with a ho- mogeneous color pattern. On dermoscopy, the lesion had a pseudoreticulum that could appear to be a melanocytic lesion (Figure 1 B). Under reflectance confocal microscopy (RCM), it showed well-defined, hyperreflective nests in the epidermis, with regular cell architecture. The cell clusters ob- served are not groups of melanocytes, as seen in nevus, but components of seborrheic keratosis. The basal layer exhib- ited acanthosis and papillomatosis, while the dermoepider- mal junction appeared irregular, without atypical or invasive features (Figure 2 A and B). LC-OCT showed well-defined, 2 Research Letter | Dermatol Pract Concept. 2025;15(3):5961 Figure 1. Seborrheic keratosis on the right thigh of the patient (A). Dermoscopic 40x view (B). Figure 2. RCM shows hyperreflective nests in the epidermis composed by homogeneous cell clusters observed (red narrows) (A). Acanthosis and papillomatosis of the basal layer (B). Vertical LC-OCT view (C) and horizontal LC-OCT view (D). Analyzed spatial reference of the lesion (E). hyper-reflective epidermal nests with regular cell structure. The epidermis was thickened, and the dermoepidermal junction appeared irregular, but no invasive or atypical fea- tures were present, distinguishing it from malignant lesions (Figure 2 C, D and E). Histological examination revealed clonal seborrheic keratosis. Discussion Accurate diagnosis of CSKs is crucial to avoiding unneces- sary excisions and misinterpretations. Recent studies have demonstrated the utility of LC-OCT in differentiating CSKs from other skin neoplasms. This technology provides valu- able morphological details, such as well-demarcated exo- phytic growth, intraepidermal pseudocysts, and the presence of polycyclic and cerebriform structures, which are highly characteristic of SKs. Furthermore, LC-OCT can distinguish between CSKs and other benign and malignant lesions based on their distinctive reflectance patterns and architectural arrangements [4]. The integration of LC-OCT with other non-invasive imaging modalities, such as dermoscopy and RCM, enhances diagnostic precision and facilitates better lesion characterization. By improving early and accurate di- agnosis, LC-OCT reduces the need for invasive biopsies and optimizes patient management [6]. Conclusion In conclusion, RCM and LC-OCT represents a promising advancement in dermatological imaging, providing high- resolution in vivo-histology-like images that aid in the Research Letter | Dermatol Pract Concept. 2025;15(3):5961 3 diagnosis of various skin conditions, including CSKs. 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