The Role of Line-field Confocal Optical Coherence Tomography in the Diagnosis of Melanoma and Melanocytic Lesions: A Systematic Review

Line-field confocal optical coherence tomography (LC-OCT) is an emerging non-invasive imaging technique that provides real-time vertical, horizontal, and three-dimensional visualization of the skin at near-cellular resolution. We systematically reviewed the available evidence on LC-OCT in melanocytic lesions to identify diagnostic features associated with melanoma and to clarify its current clinical role. MEDLINE/PubMed, Scopus, Embase and Web of Science were searched from inception to September 2026 in accordance with PRISMA recommendations. Thirty-two studies were included, encompassing cutaneous melanoma, lentigo maligna and facial pigmented lesions, benign and atypical melanocytic lesions, and mucosal melanoma. Across studies, melanoma-associated findings included irregular or disorganized epidermal architecture, numerous or pleomorphic pagetoid cells, disruption or blurring of the dermoepidermal junction, atypical dermal nests, and clefting. In lentigo maligna and facial melanoma, peri-adnexal atypia and follicular involvement emerged as particularly relevant features, whereas mucosal melanoma was characterized by diffuse pagetoid spread, epithelial disarray, atypical junctional cells, and discohesive melanocytic nests. Benign lesions more often showed preserved epidermal architecture, a well-defined junction, organized nests, and a regular wave-like dermal pattern. However, substantial overlap was observed with atypical nevi, spitzoid lesions, blue nevi, melanosis, and other intermediate entities. Although selected studies reported promising diagnostic performance, the evidence remains heterogeneous and is largely based on small, descriptive cohorts. LC-OCT may therefore serve as a useful adjunct in clinically or dermoscopically equivocal melanocytic lesions, but prospective multicenter validation and assessment of reproducibility are required before widespread routine implementation.