黑色素瘤因其显着的形态可塑性而受到认可。一些肿瘤可能失去传统特征和/或获得非黑素细胞特征，称为未分化、去分化和转分化黑色素瘤。尽管存在这种表型变异，黑色素瘤通常会维持其癌症驱动畸变，影响 BRAF、NRAS 和 NF1 等基因。目前，人们对 DNA 甲基化谱是随着分化的丧失或变化还是在广泛的形态学转变后保留下来知之甚少。在这项研究中，我们分析了 11 例黑色素瘤病例，包括 6 名男性和 5 名女性，中位年龄为 67 岁，包括五种未分化黑色素瘤、四种转分化黑色素瘤和两种去分化黑色素瘤。未分化和转分化肿瘤要么出现在患有已知黑色素瘤的患者中，要么出现在腹股沟/腋窝，其分子改变与黑色素瘤一致。异源分化的病例在形态学和免疫组织化学上类似于软骨肉瘤、骨肉瘤、血管肉瘤和横纹肌肉瘤，而未分化的肿瘤类似于未分化的多形性肉瘤。进行甲基化分析，无监督聚类分析显示 9 个病例（5 个未分化、3 个转分化和 1 个去分化）与参考集中的传统黑色素瘤紧密聚类在一起。两个病例分别与一组表现出 H3K27me3 缺失的传统黑色素瘤分开聚类。尽管分化和表型可塑性丧失，但甲基化模式似乎保留在未分化、去分化和转分化黑色素瘤中，并代表了提高诊断精度的有用诊断工具。这些诊断上具有挑战性的病例。© 2024 作者。组织病理学由约翰·威利出版

Melanomas are recognised for their remarkable morphological plasticity. Some tumours may lose conventional features and/or acquire non-melanocytic characteristics, referred to as undifferentiated, dedifferentiated and transdifferentiated melanoma. Despite this phenotypical variability, melanomas typically maintain their cancer driver aberrations, affecting genes such as BRAF, NRAS and NF1. Currently, little is known about whether the DNA methylation profile follows the loss or change of differentiation or is retained despite extensive morphological transformation.In this study we analysed 11 melanoma cases, comprising six males and five females, with a median age of 67 years, including five undifferentiated, four trans-differentiated and two de-differentiated melanomas. Undifferentiated and trans-differentiated tumours either arose in a patient with known melanoma and/or presented in the groin/axilla with molecular alterations consistent with melanoma. Cases with heterologous differentiation resembled chondrosarcoma, osteosarcoma, angiosarcoma and rhabdomyosarcoma both morphologically and immunohistochemically, while undifferentiated tumours resembled undifferentiated pleomorphic sarcoma. Methylome profiling was performed, and unsupervised clustering analysis revealed nine cases (five undifferentiated, three trans-differentiated and one de-differentiated) to cluster closely together with conventional melanomas from a reference set. Two cases clustered separately with a distinct group of conventional melanomas exhibiting H3K27me3 loss.Despite loss of differentiation and phenotypical plasticity, methylation patterns seem to be retained in undifferentiated, de-differentiated and trans-differentiated melanomas and represent useful diagnostic tools to enhance diagnostic precision in these diagnostically challenging cases.© 2024 The Author(s). Histopathology published by John Wiley & Sons Ltd.