Primary Cutaneous Peripheral T-Cell Lymphoma With Follicular Helper T-Cell Phenotype

An otherwise healthy 82-year-old woman presented with recurrent, asymptomatic erythematous papulo-nodular lesions on the face and extremities. A skin biopsy revealed a dense, non-epidermotropic lymphohistiocytic infiltrate with granulomatous features and a mixed population of medium-sized atypical lymphoid cells and plasma cells. Immunohistochemistry demonstrated a predominant CD4+ T-cell population with a T-follicular helper (TFH) phenotype (PD1+, CXCL13+, BCL6+), admixed with EBV-negative monotypic B-cells. Clonality was confirmed for both T and B cells by BIOMED2 PCR, and a RHOA p.G17V mutation was identified. Next-generation sequencing revealed additional mutations in TET2 and DNMT3A. Complete staging studies showed no nodal or visceral involvement. A minimal circulating population (0.11%) of atypical CD4+ T-cells with surface CD3 loss and TFH markers was detected in peripheral blood. Based on clinical and histopathological findings, a diagnosis of primary cutaneous peripheral T-cell lymphoma with TFH phenotype (pcPTCL-TFH) was made. The patient also developed a cutaneous squamous cell carcinoma, in which a peritumoral TFH lymphoid infiltrate with the same clonal features was identified. This case illustrates the diagnostic complexity of pcPTCL-TFH and its potential overlap with systemic TFH-derived lymphomas, underscoring the need for molecular work-up and close clinical follow-up to detect possible extracutaneous progression.