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

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.