Transformed mycosis fungoides: Biological heterogeneity, clinicopathological features, and prognostic determinants

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. A subset of patients develops large cell transformation, a biological and histopathological event associated with advanced-stage disease and poor outcomes. This narrative review summarizes current evidence on the biology, clinicopathological features, prognostic factors, and therapeutic implications of transformed MF. Available data indicate that transformation reflects clonal evolution accompanied by genomic instability, dysregulated oncogenic signaling, and gene-expression signatures consistent with an immunosuppressive tumor microenvironment. The most consistently reported adverse prognostic factors include advanced clinical stage, older age, elevated serum lactate dehydrogenase, and absent or low CD30 expression, while emerging biomarkers such as GATA3 may further refine risk stratification. Although treatment generally follows the principles of advanced MF, localized radiotherapy, CD30-directed therapy, and early consideration of allogeneic hematopoietic cell transplantation have particular relevance. Future advances will depend on biomarker-driven risk stratification and prospective studies dedicated to transformed MF.