[Melanocytomas : Intermediate melanocytic neoplasms with distinct morphology and molecular background]

As early as the 1990s, Vogelstein demonstrated that oncogenesis is often initiated by an initial "driver mutation," followed by the accumulation of additional genetic alterations during tumor progression. In both nevi and melanoma, BRAF V600E frequently represents this driver mutation, while additional "second hits" determine the risk of progression to melanoma.The 5th edition of the WHO Classification of Skin Tumours introduced the term melanocytoma (MZ). This group includes WNT-activated deep penetrating/plexiform melanocytomas (DPN), pigmented epithelioid melanocytomas (PEM), BAP1-inactivated melanocytomas (BIM), and MITF pathway-activated melanocytic tumors. All melanocytomas share an intermediate biological behavior between benign nevi and melanoma, with a low risk of progression, characteristic histopathological features, and a defined molecular background. This often includes a BRAF V600E or MAP2K1 mutation, along with a second hit involving activation of an additional signaling pathway.Melanocytomas are classified within risk group 2 of melanocytic neoplasia stratification and should be completely excised. Distinguishing them from melanoma can be challenging in some cases; in such situations, a surgical margin of up to 1 cm may be recommended. In borderline lesions with uncertain biological potential, additional molecular analyses-such as next-generation sequencing-are often helpful. Findings suggestive of melanoma include homozygous p16 deletion, TERT promoter mutation, or more than six chromosomal copy number alterations.