Peripheral T-cell lymphomas with a follicular growth pattern are derived from follicular helper T cells (TFH) and may show overlapping features with angioimmunoblastic T-cell lymphomas

Abstract

Rare cases of peripheral T-cell lymphomas with follicular growth pattern (PTCL-F) have been recently reported, and their association with t(5;9)(q33;q22) involving ITK and SYK has been suggested. However, the clinicopathologic aspects of PTCL-F are poorly described and the normal cell counterpart of this subgroup of lymphoma is still unknown. Therefore, we analyzed the pathologic, phenotypic, and cytogenetic features of a series of 30 patients (range: 33 to 88 y) that showed histopathologic features of PTCL-F in at least 1 biopsy (n=30), either at initial presentation (n=26) or at relapse (n=4). Neoplastic cells were medium-sized clear cells that were CD4+ (24/27, 89%), CD10+ (21/29, 72%), BCL-6+ (14/19, 74%), and expressed programed death-1 (27/27, 100%), CXCL13 (23/27, 85%), and ICOS (11/11, 100%), markers of follicular helper T cells (TFH). Four of 22 patients (18%) had t(5;9)(q33;q22) detected by fluorescence in situ hybridization. Patients with clinical data available had multiple lymphadenopathies (25/28, 89%), stage III to IV diseases (17/26, 65%), B symptoms (7/27, 26%), and skin lesions (6/23, 26%). Three patients with sequential biopsies disclosed clinical and histopathologic features of angioimmunoblastic T-cell lymphoma at initial presentation. Our results show that this rare form of PTCL-F (1) has an immunophenotype indicative of derivation from TFH cells, (2) is associated with t(5;9) in a proportion of cases, and (3) shows some overlapping features with angioimmunoblastic T-cell lymphoma, raising the question of a possible relationship.

Figure 1

Two types of peripheral T-cell lymphoma with follicular growth pattern. A, Hematoxylin and eosin (H&E)-stained sections showing a follicular lymphoma-like PTCL-F (#1) characterized by numerous nodules in a back-to-back fashion mimicking a follicular lymphoma, composed of medium-sized neoplastic cells with clear cytoplasm and irregular nuclei (inset). The neoplastic cells are surrounded by (B) CD20+ B cells and positive for (C) CD5 and CXCL13 (inset, #8). D, H&E sections showing a progressive transformation of germinal center-like PTCL-F (#29) characterized by small aggregates of neoplastic cells dispersed in large irregular nodules mimicking progressive transformation of germinal center. The inset shows that the neoplastic cells have irregular nuclei and clear cytoplasm. The neoplastic cells are surrounded by (E) IgD+ small, mature B cells and positive for (F) CD3 and CXCL13 (inset, #15). G and H, H&E sections showing features of (G) angioimmunoblastic T-cell lymphoma in the first episode then relapsed as (H) PTCL-F in patient #15. I, FISH for the detection of the t(5;9)/ITK-SYK. Separate green and red signals for ITK (left panel) and SYK (right panel) demonstrate rearrangements of the genes in a t(5;9)/ITK-SYK positive patient (#5-1^st). (Original magnification A and D x2.5; B, C, E, and F, x10; G, and H, x25; A inset, C inset, D inset, and F inset, x40).