Melanoma is the most dangerous form of skin cancer that develops from the malignant transformation of the melanocytes located in the basal layer of the epidermis (cutaneous melanoma). Melanocytes may also be found in the meninges, eyes, ears, gastrointestinal tract, genito-urinary system, or other mucosal surfaces (mucosal melanoma). Melanoma is caused by an uncontrolled proliferation of melanocytes, that at first may form a benign lesion (nevogenesis), but in time, it may transition to melanoma, determining what it is named, melanomagenesis. Some tumors may appear spontaneously (de novo melanoma) or on preexisting lesions (nevus-associated melanoma). The exact cause of melanoma may not be fully understood yet, but there are some factors that initiate and promote this malignant process. This study aims to provide a summary of the latest articles regarding the key factors that may lead to melanomagenesis. The secondary objectives are to reveal the relationship between nevi and melanoma, to understand the cause of “de novo” and “nevus-associated melanoma” and highlight the differences between these subtypes.

Dermoscopy is a non-invasive method of examination that aids the clinician in many ways, especially in early skin cancer detection. Melanoma is one of the most aggressive forms of skin cancer that can affect individuals of any age, having an increasing incidence worldwide. The gold standard for melanoma diagnosis is histopathological examination, but dermoscopy is also very important for its detection. To highlight the many roles of dermoscopy, we analyzed 200 melanocytic lesions. The main objective of this study was to detect through dermoscopy hints of melanomagenesis in the studied lot. The most suspicious were 10 lesions which proved to be melanomas confirmed through histopathology. The second objective of this study was to establish if dermoscopy can aid in estimating the Breslow index (tumoral thickness) of the melanomas and to compare the results to the histopathological examination. We found that the tumoral thickness may be estimated through dermoscopy, but the histopathological examination is superior. To conclude, the aim of this study was to showcase the versatility and many roles of dermoscopy, besides being one of the most important tools for early melanoma diagnosis.

Aim and objectives: Melanoma is one of the most complex skin cancers based on its numerous somatic mutations and chromosomal instability. Besides the traditional causative factors, such as ultraviolet radiation, or genetic factors, recent studies showed that melanoma highly depends on its adjacent microenvironment. A malignant tumor, like melanoma, is composed of oncogenic cells, regular cells (melanocytes, macrophages, mast cells, keratinocytes, and others), the supporting stroma, which includes fibroblasts, endothelial cells, immune cells, soluble molecules, and the extracellular matrix (ECM). This article aims to present the tumor microenvironment's main functions in the development or progression of melanoma. Material and methods: we have studied some of the most recent 30 articles based on the role of the microenvironment in melanoma. Results: After analyzing the most recent articles regarding melanoma’s tumor microenvironment (TME) and its impact, we have found that the cells that comprise the TME can affect melanoma’s onset or progression. TME’s cells actively interact with each other and have many functions, from tumor-suppressing roles to the initiation or progression of melanoma. Conclusions: Understanding the complex interplay between tumor cells, and systemic mediators of disease progression is critical for the rational development of effective melanoma treatments. Each cell involved in the TME can play an important role either in the onset or advancement of melanoma with the help of certain mutagenic factors.

Background and Objectives: Angiogenesis plays an important role in many types of cancers, including melanoma. Mast cells are among the most important cellular partners involved in the angiogenic process. The purpose of the present study is to establish the interrelations between microvessels and mast cell density, and to describe the prognostic role of mast cells in malignant melanoma. Materials and Methods: A total of 92 cases of melanoma were evaluated. Hematoxylin–eosin staining and CD34/mast cell tryptase double immunostaining were performed. Results: Of the cases, 28 were classified as T1 (30.43%), 31 as T2 (33.69%), 21 as T3 (22.82%), and 12 as T4 (13.04%). Mast cells were mainly located in the infiltrate area in cases with inflammatory infiltrate. Few mast cells were observed in the absence of infiltrate. A granular type was observed in intratumoral areas with an isolated and perivascular distribution of mast cells. A significant correlation was found between intratumoral MVD and intratumoral MCD (mast cell density) in T1 and T4 melanoma cases (p = 0.0001 and p = 0.0029, respectively). In T2 cases, significant correlations were found between intratumoral and peritumoral MVD and G (p = 0.0169, p = 0.0003), between intratumoral MCD and MVD (p = 0.0041), and between peritumoral MVD and the number of peritumoral mast cells (p = 0.0011). T3 cases showed a significant correlation between the density of intratumoral mast cells and peritumoral ones (p = 0.001); between the MVD and mast cell density of the intratumoral area (p = 0.0001); between the intratumoral MVD and peritumoral mast cell density (p = 0.0001); between the MVD and mast cell density of the peritumoral area (p = 0.0325); and between the peritumoral MVD and intratumoral mast cell density (p = 0.0458). Conclusions: Both intratumoral and peritumoral mast cells were found to participate in melanoma progression, and they showed greater involvement in the early phases of angiogenesis in malignant melanoma.

Melanocytic lesions frequently present diagnostic challenges due to their high degree of morphological heterogeneity. While histopathological examination remains the gold standard for melanoma diagnosis, alternative methods, such as fluorescence in situ hybridization (FISH), are used to support diagnosis in uncertain cases. FISH is a complementary diagnostic tool that can help differentiate between nevi and melanoma by detecting chromosomal anomalies. However, its accuracy is limited by false‑positive and false‑negative results. The present study assessed the utility and limitations of FISH in melanoma diagnosis by analyzing chromosomal anomalies in 18 melanocytic lesions previously classified as atypical nevi or melanoma based on dermoscopic and histopathological criteria. The results revealed that FISH confirmed nearly all atypical nevi as benign lesions (with the exception of one lesion); however, it failed to definitively confirm all melanomas. These findings highlight both the strengths and weaknesses of FISH, suggesting that while it is a useful adjunctive tool, it should not replace conventional histopathological examination. Instead, FISH should be interpreted with caution due to its potential for false‑positive and false‑negative results, underscoring the need for further studies to refine its diagnostic reliability.