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

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.