Cutaneous melanoma is the most severe form of skin cancer. The incidence of the disease has been increasing in the last decades, largely due to increased ultraviolet radiation exposure. A comprehensive understanding of the complex biological processes involved in melanoma development and progression is essential for advancing patient care. Improvement in surveillance strategies, widespread use of sentinel lymph node biopsy, and breakthroughs in systemic therapy have all contributed considerably to enhancing patient outcomes and survival. Rapid advancements in melanoma management are expected to continue, particularly through innovations in molecular biology and genetics. These emerging technologies aim to enhance diagnostic accuracy, predict disease progression, and improve prognosis. Staying informed about these evolving developments is essential for professionals dealing with melanoma patients. This narrative review provides a comprehensive overview of the current state of cutaneous melanoma, covering fundamental areas, such as histopathology, genetics, epidemiology, diagnosis, and staging. It provides a foundation to enhance understanding of current treatment approaches and the principles behind emerging technologies. This review also highlights future directions in melanoma care, including improvements in neoadjuvant therapy, use of artificial intelligence-based algorithms, use of molecular biomarkers to improve diagnosis and prognosis, and development of personalized neoantigen mRNA vaccines. Ultimately, this review aims to support clinicians in understanding the current landscape and anticipated innovations in melanoma management to improve clinical decision-making.

Background/ Objectives: Melanoma is the most severe form of skin cancer, with incidence increasing worldwide. However, there is still a lack of strong evidence to support melanoma screening, and screening strategies vary among healthcare systems. This study aims to compare the effectiveness of two strategies, total-body screening (TBS) examination and lesion-directed examination (LDE) of a suspicious lesion, in detecting melanoma at earlier stages (thickness<0.8mm). Methods: Data was collected from all patients who came for dermatology visits, whose appointment reason was either a TBS visit or a LDE of a suspicious melanoma lesion. All visits were performed at Ospedale Maggiore Policlinico, Milan, Italy, between October and December 2023. Results: 1116 patients were included in the cohort (866 came for TBS, 250 came for LDE) and 19 melanomas were histologically confirmed (10 in the TBS group, 9 in the LDE group). Positive predictive value was 26.7%. Melanomas were diagnosed more often in male sex (73.7%; p=0.013) and in older patients (mean age 64.5 years old; p=0.016). Patients in the TBS group were younger and more frequently associated with a positive risk factor for melanoma, compared to patients in the LDE group (p<0.001). Even though thicker melanomas (≥0.8mm) were found more often in patients who came for LDE visits, this finding was not confirmed to be statistically significant (p=0.350). TBS visits were, therefore, not associated with the diagnosis of melanoma at earlier stages. Among patients with melanoma diagnosis, no demographic, histologic or clinical characteristics were different between TBS and LDE groups. Conclusions: Lesion-directed examination, when performed by dermatologists, can be an alternative to standard total-body screening visits for the detection of melanoma at earlier stages in the general population.