Gamma-Delta Phenotypic Evolution in Mycosis Fungoides With CD30-Positive Cutaneous Progression

CD30-positive large-cell proliferations arising in patients with mycosis fungoides can be diagnostically challenging, particularly when they show variable T-cell receptor expression or gamma/delta (γδ) phenotype. We present two cases of mycosis fungoides (MF) with CD30-positive large cell transformation (LCT)/progression exhibiting γδ T-cell phenotypic evolution. Case 1, a 50-year-old woman, initially presented with hyperpigmented patches and papulonodular lesions showing epidermotropic small-cell MF alongside dermal CD30-positive large cells with a γδ phenotype. Over ten years, she developed recurrent cutaneous and eventually nodal disease with phenotypic shifts between γδ and αβ expression, while molecular studies confirmed a single clonal process across all biopsies. Potentially pathogenic variants in FAS and CD70 were identified. Case 2, a 72-year-old man with longstanding MF, developed CD30-positive LCT initially with an αβ phenotype that subsequently acquired γδ expression and DUSP22 rearrangement. Oncoscan microarray revealed shared copy-number alterations including CDKN2A/B loss across temporally distinct biopsies, and sequencing identified KMT2C and TET1 variants. Both cases illustrate that MF can exhibit dynamic T-cell receptor phenotypic evolution, posing significant diagnostic challenges with lymphomatoid papulosis and primary cutaneous γδ T-cell lymphoma. Clonal identity confirmation through molecular studies is essential for accurate classification.