In vivo reflectance confocal microscopy role for early to advanced lentigo maligna melanoma spectrum: A systematic review and pooled analysis.

Lentigo maligna (LM) is a growing problem worldwide and the main type of melanoma in situ in some Caucasian populations. It presents as a spectrum from atypical intraepidermal melanocytic proliferation (AIMP) to invasive lentigo maligna melanoma (LMM). Accurate diagnosis and staging are crucial for determining appropriate management strategies. To assess the role of in vivo reflectance confocal microscopy (RCM) in differentiating early and advanced stages of lentigo maligna. A systematic search was conducted on Medline, PubMed, Scopus, Web of Science, Proquest Central, Embase, Cochrane and Google Scholar. References of included and excluded studies were reviewed for additional sources. Studies involving RCM for AIMP, LM and LMM diagnosis published until 1 December 2023, were selected for analysis. Publications on other non-invasive imaging techniques, other skin diseases or those addressing only RCM surgical margins and therapeutic response without reporting RCM features were excluded. Each article was reviewed by two experts, with disagreements resolved by a third expert. Data for each RCM feature were pooled, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Features were stratified for architecture, cellular morphology and distribution. Twenty-seven articles involving 303 lesions were included. Features favouring LM over AIMP included (1) Architecture: the presence of non-edged papillae (OR 4.50, 95% CI 1.92-10.52) and (2) Cellular distribution: widespread pagetoid cells and junctional atypical cells (OR 25.06, 95% CI 4.19-148.45) and junctional nests (OR 18.06, 95% CI 3.04-106.32). Features favouring LMM over LM included (1) Architecture: epidermal disarray (OR 5.03, 95% CI 1.90-13.22), junctional disarray (OR 4.19, 95% CI 1.54-11.33) and destroyed collagen fibres (OR 3.91, 95% CI 1.80-8.44) and (2) cellular distribution: widespread pagetoid and junctional atypical cells (OR 2.71, 95% CI 1.27-5.75) and junctional nests (OR 4.48, 95% CI 2.12-9.43). This study identifies the RCM features associated with the LM/LMM spectrum.