Distinct and overlapping features of nodal peripheral T-cell lymphomas exhibiting a follicular helper T-cell phenotype: a multicenter study emphasizing the clinicopathological significance of follicular helper T-cell marker expression

Nodal peripheral T-cell lymphoma (PTCL) is a heterogeneous category including angioimmunoblastic T-cell lymphoma (AITL), PTCL of follicular helper T-cell (Tfh) phenotype (PTCL-Tfh), and PTCL, not otherwise specified (PTCL-NOS). We explored Tfh marker profiles in nodal PTCL. Nodal PTCLs (n = 129) were reclassified into AITL (58%; 75/129), PTCL-Tfh (26%; 34/129), and PTCL-NOS (16%; 20/129). Histologically, clear cell clusters, high endothelial venules, follicular dendritic cell proliferation, EBV+ cells, and Hodgkin-Reed-Sternberg (HRS)-like cells were more common in AITL than PTCL-Tfh (HRS-like cells, P =.005; otherwise, P <.001) and PTCL-NOS (HRS-like cells, P =.028; otherwise, P <.001). PTCL-NOS had a higher Ki-67 index than AITL (P =.001) and PTCL-Tfh (P =.002). Clinically, AITL had frequent B symptoms (versus PTCL-Tfh, P =.010), while PTCL-NOS exhibited low stage (versus AITL + PTCL-Tfh, P =.036). Positive Tfh markers were greater in AITL (3.5 ± 1.1) than PTCL-Tfh (2.9 ± 0.9; P =.006) and PTCL-NOS (0.5 ± 0.5; P <.001). Tfh markers showed close correlations among them and AITL-defining histology. By clustering analysis, AITL and PTCL-NOS were relatively exclusively clustered, while PTCL-Tfh overlapped with them. Survival was not different among the PTCL entities. By Cox regression, sex and ECOG performance status (PS) independently predicted shorter progression-free survival in the whole cohort (male, P =.001, HR = 2.5; PS ≥ 2, P =.010, HR = 1.9) and in ‘Tfh-lymphomas’ (ie, AITL + PTCL-Tfh) (male, P =.001, HR = 2.6; PS ≥ 2, P =.016, HR = 2.1), while only PS predicted shorter overall survival (OS) in the whole cohort (P =.012, HR = 2.7) and in ‘Tfh-lymphomas’ (P =.001; HR = 3.2). ICOS predicted favorable OS in ‘Tfh-lymphomas’ (log-rank; P =.016). Despite the overlapping features, nodal PTCL entities could be characterized by Tfh markers revealing clinicopathologic implications.