Primary Cutaneous Peripheral T‐Cell Lymphoma With TFH Phenotype With Divergent Clonal B‐ and Plasma‐Cell Populations and DNMT3A Mutation

ABSTRACT Primary cutaneous peripheral T‐cell lymphoma with T‐follicular helper phenotype (pcTFH‐PTCL) is rare, and concurrent clonal B‐lineage proliferations are uncommon. This lymphoma subtype presents unique diagnostic challenges due to its rarity and potential for misdiagnosis. We present a case of pcTFH‐PTCL in an 88‐year‐old man with pruritic nodules on the shoulders, later developing multifocal cutaneous lesions including a prominent eyebrow nodule. Biopsies showed dense dermal infiltrates of CD4 positive T cells expressing TFH markers (PD‐1, ICOS, and BCL6). Three lesions demonstrated an identical clonal T‐cell receptor (TCR) gene rearrangement, confirming a clonal T‐cell process. Remarkably, accompanying B‐lineage components varied: lambda‐restricted plasma cells and kappa‐restricted B cells were identified in multiple lesions. Clonality studies revealed mostly distinct immunoglobulin heavy chain (IGH) rearrangements across separate sites, indicating independent B‐cell clones. Whole exome sequencing revealed a pathogenic DNMT3A p.Arg882Cys mutation in two different biopsy sites. This case represents a rare pcTFH‐PTCL with a persistent T‐cell clone coexisting with divergent clonal B‐ and plasma cell populations. The findings emphasize the role of TFH‐derived neoplasms in fostering B‐cell expansions and highlight the diagnostic and therapeutic complexity posed by dual‐lineage clonality in cutaneous lymphomas.