黑色素瘤发病机制通常被认为是分子变化的线性积累，揭示了由非线性生物过程驱动的显着异质性，包括黑素细胞干细胞的直接转化。这种异质性体现在不同的生物表型和发育状态中，影响对治疗的不同反应。揭示控制黑色素瘤发生、进展和转移的异常机制势在必行。除了致癌基因和肿瘤抑制基因的突变之外，不同分子途径的参与在黑色素瘤发病机制中发挥着关键作用。紫外线 (UV) 辐射是黑色素瘤病因学的主要因素，它根据累积阳光损伤 (CSD) 对黑色素瘤进行分类。病变的基因组景观与紫外线暴露相关，影响突变负荷和突变谱。世界卫生组织 2018 年的分类强调了阳光照射与基因组特征之间的相互作用，将与 CSD 相关的黑色素瘤与与 CSD 无关的黑色素瘤区分开来。该分类阐明了分子特征，例如与不同黑色素瘤亚型相关的肿瘤突变负荷和拷贝数改变。突变的 BRAF 基因及其通路，特别是 BRAFV600 变体，在黑色素瘤中的重要性至关重要。 BRAF 突变在多种癌症类型中普遍存在，提供了治疗途径，临床试验验证了靶向治疗和免疫治疗的功效。癌基因中的其他驱动突变进一步表征了特定的黑色素瘤途径，影响肿瘤行为。虽然组织病理学检查仍然至关重要，但对黑素细胞肿瘤进行分子分类仍然存在挑战。在这篇综述中，我们回顾了所有有助于区分常见和模糊病变的分子表征。将高度敏感的分子诊断测试整合到诊断工作流程中变得必不可少，特别是在仅靠组织学无法得出结论性诊断的情况下。本文提出了一种基于各种研究推断出的不同分子特征的诊断算法。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Melanoma pathogenesis, conventionally perceived as a linear accumulation of molecular changes, discloses substantial heterogeneity driven by non-linear biological processes, including the direct transformation of melanocyte stem cells. This heterogeneity manifests in diverse biological phenotypes and developmental states, influencing variable responses to treatments. Unveiling the aberrant mechanisms steering melanoma initiation, progression, and metastasis is imperative. Beyond mutations in oncogenic and tumor suppressor genes, the involvement of distinct molecular pathways assumes a pivotal role in melanoma pathogenesis. Ultraviolet (UV) radiations, a principal factor in melanoma etiology, categorizes melanomas based on cumulative sun damage (CSD). The genomic landscape of lesions correlates with UV exposure, impacting mutational load and spectrum of mutations. The World Health Organization's 2018 classification underscores the interplay between sun exposure and genomic characteristics, distinguishing melanomas associated with CSD from those unrelated to CSD. The classification elucidates molecular features such as tumor mutational burden and copy number alterations associated with different melanoma subtypes. The significance of the mutated BRAF gene and its pathway, notably BRAFV600 variants, in melanoma is paramount. BRAF mutations, prevalent across diverse cancer types, present therapeutic avenues, with clinical trials validating the efficacy of targeted therapies and immunotherapy. Additional driver mutations in oncogenes further characterize specific melanoma pathways, impacting tumor behavior. While histopathological examination remains pivotal, challenges persist in molecularly classifying melanocytic tumors. In this review, we went through all molecular characterization that aid in discriminating common and ambiguous lesions. Integration of highly sensitive molecular diagnostic tests into the diagnostic workflow becomes indispensable, particularly in instances where histology alone fails to achieve a conclusive diagnosis. A diagnostic algorithm based on different molecular features inferred by the various studies is here proposed.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.