Follicular T-Helper Cells in Marginal Zone Lymphoma: Evidence of an Organoid Immune Response

Introduction: Primary cutaneous marginal zone B-cell lymphoma (MZL) follows an indolent clinical course. Histopathologically, there is a polymorphous infiltrate that includes small lymphocyte-like and centrocyte-like B cells and plasma cells usually with a substantial T-cell fraction. Primary cutaneous CD4 + small/medium T-cell lymphoproliferative disorder, in which the signature cells have a follicular T-helper (TFH) phenotype and are admixed with numerous B cells. Thus, both present histologies of combined B-cell and T-cell infiltrates and represent differential diagnoses. The presence of TFH in MZL has yet to be elucidated. Methods: Forty-one biopsies from 40 cases of MZL and 7 cases of lymphoid hyperplasia cutis (LCH) were stained with antibodies to follicular T-helper cells, including Bcl-6, PD-1, ICOS, and CD10, as part of their diagnostic workup, were reviewed, and the stained slides were evaluated semiquantitively. Five reactive lymph nodes were also evaluated as controls. Results: All cases of MZL and LCH contained TFH, albeit usually in low proportions. There were repeated differences in levels of expression between TFH markers, with PD1 and Bcl-6 being the most prevalent. The pattern of involvement in MZL and LCH closely mirrored that observed in the reactive lymph nodes. Conclusion: MZL includes TFH cells, similar to reactive lymph nodes, and a complexity of cell types. This provides evidence of an organoid immune response challenging its simple categorization as a malignancy.