Abstract
Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoproliferative disorder (CD4+ PCSM-LPD) is characterized by its indolent course and favorable prognosis, distinguishing it from multifocal variants or other peripheral T-cell lymphomas. Pediatric cases are exceptionally rare, with only 9 pediatric cases documented, limiting understanding of their clinical, pathological, and molecular characteristics. Although recent studies propose a T follicular helper cell (TFH) origin, further investigation is necessary to substantiate this hypothesis and elucidate the pathogenesis of CD4+ PCSM-LPD in pediatric patients. We conducted a systematic literature review (6 studies documenting 9 cases) and retrospective chart review of pediatric CD4+ PCSM-LPD cases (≤21 years) diagnosed at Weill Cornell Medicine between 2010 and 2024 (4 cases). All 13 cases presented with solitary lesions, lacking the head and neck predominance observed in adult patients. Treatments included intralesional steroids, excision, and local radiation, with no recurrences. Histopathology mirrored adult cases, showing characteristic features of CD4+ PCSM-LPD. Nonspecific TFH markers (PD-1, BCL-6, ICOS) exhibited variable positivity, whereas specific markers (CD10, CXCL13) were predominantly negative. CD4+ PCSM-LPD is a rare entity that can potentially occur in pediatric patients, exhibiting clinical, histopathological, and phenotypic features similar to adult cases. However, the hypothesis of follicular helper T-cell ontogeny is questioned, as specific markers are usually absent, whereas commonly reported positive stains are not specific for follicular helper T cells. This suggests a malleable CD4+ T-cell phenotype influenced by the microenvironment.