ArticleHistopathology2025
The utility of DNA methylation profiling in the diagnosis of un-, de- and trans-differentiated melanoma: a series of 11 cases.
Article in Histopathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- DNA Methylation Signatures of Upper Aerodigestive Tract Squamous Cell Carcinoma and Sarcomatoid Squamous Cell Carcinoma Are Similar: A Potential Novel Diagnostic Tool for the Diagnosis of Sarcomatoid Squamous Cell Carcinoma.Head and neck pathology · 2026Article
- Pitfalls in Bone and Soft Tissue Pathology of the Head and Neck: Primary Intraosseous Rhabdomyosarcoma/FUS::TFCP2-Rearranged Spindle Cell Rhabdomyosarcoma and Transdifferentiated/Dedifferentiated/Undifferentiated Melanoma.Head and neck pathology · 2026Review
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7 authors.
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Abstract
aimsMelanomas 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. METHODS AND
resultsIn 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.
conclusionsDespite 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.
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