Primary Cutaneous CD4+ Small/Medium-Sized T-Cell Lymphoproliferative Disorder: A Retrospective Cohort Study of 40 Adult Patients.

Primary cutaneous CD4+ small/medium-sized T-cell lymphoproliferative disorder (CD4+ PCSM-LPD) is distinguished from other peripheral T-cell lymphomas, particularly multifocal variants, by its indolent clinical behavior and favorable prognosis. Recent studies have suggested a T follicular helper (TFH) cell origin for these lesions; however, further studies are warranted to substantiate this hypothesis and clarify their pathogenesis. A retrospective review was conducted of all adult cases of CD4+ PCSM-LPD diagnosed at Weill Cornell Medicine between 2018 and 2024. The aim of this study was to evaluate the clinical, pathological, and molecular characteristics of these cases, with a specific focus on exploring the hypothesis of a follicular helper T-cell origin in CD4+ PCSM-LPD. Forty patients (26 men, 14 women) were encountered (age 25-83 years at presentation). Except for 1 oligolesional case, all others presented with solitary lesions, most frequently involving the head and neck region (26 of 37 cases, 72.2%). Treatment included surgical excision or radiation alone, with 1 lesion resolving spontaneously following the initial biopsy. Recurrence occurred only in 1 oligolesional case. All cases displayed characteristic histopathology of CD4+ PCSM-LPD. Varying positivity for nonspecific TFH markers (PD-1, BCL-6 and ICOS) was observed; both PD1 and ICOS can be expressed by activated T cells. Specific markers, CD10 and CXCL13, were predominantly negative the staining profile of CD4+ PCSM-LPD therefore suggests a partially developed TFH phenotype, reflecting the dynamic acquisition of these markers by neoplastic T cells in a conducive monocyte derived CD11c dendritic cell enriched microenvironment. Light chain restriction for plasma cells was observed in a qaurter of the cases and reflects the role of plasma cells as a countercheck population controlling follicular helper T cell expansion. Finally the lack of a follicular helper T cell phenotype in select cases that are otherwise typical for CD4+ PCSM-LPD should not exclude the diagnosis.