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Lentigo maligna (LM) and its invasive form, lentigo maligna melanoma (LMM), often occur in sun-exposed areas and are characterized by subclinical extension, thereby complicating margin delineation. Reflectance confocal microscopy (RCM) has emerged as a non-invasive imaging tool for presurgical mapping of such lesions. The objective is to evaluate the impact of RCM on surgical outcomes in LM/LMM compared to standard clinical and dermoscopic assessment.

We conducted a retrospective comparative cohort monocentric study by including 282 patients treated for LM or LMM between 2018 and 2025. Patients were divided into 2 groups: 184 who underwent presurgical RCM mapping (RCM group), and 98 who received standard care without RCM (non-RCM group). Surgical outcomes—including number of procedures, surgical margin, and recurrence rates—were compared between the groups.

The rate of complete excision after a single procedure was significantly higher in the RCM group (63.6%) compared to the non-RCM group (34.7%, p < 0.0001). Patients in the RCM group required fewer surgical stages (mean 1.18 vs. 1.94; p < 0.0001) and narrower margins (mean 5.2 mm vs. 6.2 mm; p = 0.002). These benefits were especially notable in complex facial subregions. Median follow-up durations were comparable between the groups (1096.5 vs. 1167.5 days; p = 0.27).

RCM-guided surgery improved margin control and surgical efficiency in LM and LMM, especially in anatomically complex regions. These results support the integration of RCM into routine preoperative planning for LM/LMM.

The role of lymph node dissection (LND) in melanoma has evolved substantially following publication of the MSLT-II trial and the introduction of effective adjuvant immunotherapy. These developments rendered routine completion LND obsolete. Real-world evidence describing changes in surgical indications, morbidity, adjuvant treatment, and survival remains limited. This study aimed to evaluate era-dependent changes in LND and their outcomes in a tertiary melanoma cohort.

A retrospective single-center cohort study included melanoma patients undergoing regional LND between 2011 and 2023. Patients were stratified into two periods (2011–2016 vs. 2017–2023) reflecting pre- and post-MSLT-II paradigms. Variables analyzed included indication for LND (therapeutic vs. completion), extracapsular extension (ECE), postoperative complications (Clavien–Dindo), recurrence, adjuvant therapy, and overall survival (OS). Recurrence was defined as any local, regional, or distant relapse. OS was calculated from date of LND to death or last follow-up using Kaplan–Meier analysis with log-rank comparison.

A total of 135 patients were analyzed (2011–2016: n=48; 2017–2023: n=87). Therapeutic LND increased markedly in the contemporary period (29% vs. 89%). ECE was observed in 35% and 43% of patients, respectively, while recurrence rates were comparable (52% vs. 49%). Adjuvant systemic therapy increased from 32% to 82%, whereas adjuvant radiotherapy decreased from 66% to 34%. Clavien–Dindo grade II, IIIa, and IIIb complications occurred in 12%, 12%, and 6% of patients in 2011–2016 compared with 7%, 15%, and 16% in 2017–2023, corresponding to major complication rates of 19% and 31%, respectively. One- and three-year OS were 98% and 77% in the earlier period versus 90% and 69% in the contemporary period, with no significant survival difference observed (log-rank p=0.57).

Melanoma lymph node dissection has transitioned to a predominantly therapeutic intervention within a modern multimodal treatment landscape characterized by increased immunotherapy use and reduction in adjuvant radiotherapy. Despite treatment of biologically higher-risk disease and increased major morbidity, recurrence rates and survival outcomes remained comparable, supporting the use of therapeutic lymph node dissection alone in contemporary melanoma management.

Cutaneous melanoma demonstrates significant heterogeneity in clinical behavior despite similar staging. Angiogenesis is a key driver of melanoma progression and may also influence tumor immune evasion. Improved biological stratification could refine surgical decision-making and adjuvant treatment planning. We investigated the prognostic and immunological relevance of angiogenesis-related genes in primary and metastatic skin melanoma.

Thirty-six angiogenesis-related genes were analyzed in TCGA-SKCM cohorts, separately for primary and metastatic tumors. Gene expression was correlated with overall survival, disease-specific survival, and progression-free interval using Cox regression and Kaplan-Meier analysis. Tumor immune contexture was evaluated using multiple established immune deconvolution approaches and immune checkpoint gene profiling.

Distinct stage-specific prognostic signatures were identified. S100A4, ITGAV, TIMP1, VEGFA and COL3A1 demonstrated significant associations with survival outcomes. Several genes showed differential expression between tumor and normal tissue and exhibited consistent correlations with immune suppressive phenotypes, including reduced cytotoxic T cell infiltration and increased macrophage-associated signatures. Immune associations differed between primary and metastatic cohorts, suggesting biologically distinct microenvironments across disease stages.

Angiogenesis-related gene expression is strongly associated with survival and tumor immune landscape in cutaneous melanoma. Stage-specific immune signatures may help refine biological risk stratification and support multidisciplinary decision-making, including surgical timing and adjuvant therapy selection. These findings highlight the relevance of integrating molecular profiling into melanoma surgical oncology.

Men have a significantly higher risk of developing cutaneous squamous cell carcinoma (SCC) compared to women. This difference has historically been attributed to behavior differences. Sexual hormones and their receptors however seem to play a role as well, despite limited description of the signaling pathways involved.

We developed a UV-induced SCC model in hairless mice by exposure to UV three times per week for 6 months. The severity of the induced lesions was characterized in a blinded manner both after a single dose of UV exposure and after chronic exposure. DNA damage and repair response were compared in both sexes, as well as epidermal proliferation and differentiation rates. The transcriptome of male and female mouse epidermis exposed to UV was analyzed using RNA sequencing to identify transcription factors and genes involved. The experiments were repeated on human skin samples and the impact of identified genes depletion was measured on two human squamous carcinoma cell lines in an in vivo xenograft model.

UV-induced lesion were present in 65% of the dorsal skin surface of males compared to only 27% of the dorsal skin surface of females. Lesions were also more advanced. Analysis of DNA damage and repair showed no differences between sexes but males’ epidermis showed an enhanced proliferation while female’s epidermis showed altered differentiation already 3 days after UV exposure. The E2F family of transcription factors was found to be downregulated in females only and this effect was found to be mediated by estrogen receptors. The expression of the target gene CDKN3 was reduced as well. Human skin samples showed the same UV dose-dependent reduction in E2F and CDKN3 expression. The latter was showed to have a protective effect against SCC development, most likely through blocking G1/S phase transition and thus cell cycle progression.

While UV-induced DNA damage is similar between sexes, we identified E2F transcription factors as key sex-specific markers of the proliferative response to UV and their target gene CDKN3 was selectively downregulated in female mouse and human epidermis following UV exposure through estrogen receptor mediation. Functionally, CDKN3 depletion impaired SCC cell progression into S-phase and reduced tumor growth in xenograft models.