Primary Cutaneous Follicular Helper T‐Cell Lymphoma: A Clinicopathological Study of Six Cases and Review of the Literature

ABSTRACT Background Primary cutaneous follicular helper T‐cell lymphoma (pcTFH‐L) is a rare, poorly characterized entity. We present six new cases to elucidate its clinicopathological features. Methods We retrospectively analyzed the clinical, histomorphological, and immunohistochemical features (TFH markers: PD‐1, CXCL13, BCL‐6, CD10, ICOS), EBV status, and T‐cell receptor clonality of six pcTFH‐L cases, comparing findings with 48 previously reported cases. Results The cohort (five males, one female; median age 66.5 years, range 42–75 years) presented with localized skin lesions without B symptoms or lymphadenopathy. All cases showed dermal/subcutaneous infiltration by atypical lymphocytes without epidermotropism (nodular pattern in 4 cases, diffuse pattern in 2 cases). Prominent high endothelial venules (HEVs) were exhibited in 4/6 cases. Neoplastic cells in all cases expressed CD4 and at least three TFH markers, with PD‐1 (6/6), ICOS (6/6), and CXCL13 (6/6) being the most sensitive. CD21‐positive follicular dendritic cell (FDC) networks were observed in 4 of 6 cases. Epstein–Barr virus‐encoded RNA (EBER) was positive in 4 of 6 cases, and clonal T‐cell receptor (TCR) gene rearrangements were detected in all 6 cases tested. Treatments varied from none to combination chemotherapy, with outcomes ranging from stable disease to complete remission; one patient died of heart failure, and another died at 20 months despite treatment. Conclusions This case series reinforces pcTFH‐L as a distinct cutaneous lymphoma with a characteristic immunophenotype and microenvironment. The consistent expression of multiple TFH markers, particularly PD‐1, ICOS, and CXCL13, is essential for accurate diagnosis and differentiation from other cutaneous T‐cell lymphoproliferative disorders. The clinical course appears heterogeneous, with some cases showing indolent behavior while others may have more aggressive outcomes.