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

ABSTRACT

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.