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.

Integrative clinicopathological and molecular analyses of angioimmunoblastic T-cell lymphoma and other nodal lymphomas of follicular helper T-cell origin

“…7,8 Furthermore, the rare "follicular" T-cell lymphoma (F-PTCL), initially classified as a PTCL-NOS variant, is characterized by a TFH immunophenotype and clinicopathological features overlapping with AITL. 9,10 Recently, recurrent AITL-associated TET2, DNMT3A and RHOA mutations were also found in a subset of PTCL-NOS, and tended to correlate with TFH features. 11,12 Based on these recent findings, the 2016 update of the WHO classification groups AITL and other nodal lymphomas of TFH origin under the same umbrella.…”

Follicular center helper T-cell (TFH) marker positive mycosis fungoides/Sezary syndrome

“…15,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] These include angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma with a follicular growth pattern, primary cutaneous CD4( þ ) small/ medium-sized pleomorphic T-cell lymphoma and, occasionally, peripheral T-cell lymphoma, not otherwise specified and anaplastic large cell lymphoma. 15,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Clinically, primary cutaneous CD4( þ ) small/ medium-sized pleomorphic T-cell lymphoma and angioimmunoblastic T-cell lymphoma present or may present with primary cutaneous involvement. 20,[36][37][38][39][40] Other CD4( þ ) T-cell lymphomas with primary cutaneous manifestations include mycosis fungoides and its variants including Sezary syndrome, adult T-cell leukemia/lymphoma and primary cutaneous CD30 þ lymphoproliferative disorders.…”

“…These lymphomas have morphologic findings that overlap with, and may be indistinguishable from, angioimmunoblastic T-cell lymphoma. 26 Detection of CD10 on tumor cells in skin biopsies by immunohistochemistry can be difficult due to expression of CD10 on tumor-associated dermal fibroblasts obscuring the cellular origin of the staining. 6,7,42 As an alternative to immunohistochemistry, CD10 on tumor cells can be detected by flow cytometry.…”

Peripheral T cell lymphoma in Asia

“…Clinically, the coexistence of PTCL-F and AITCL in the same patient has been reported [31]. Some patients who were initially diagnosed with AITCL relapsed with PTCL-F [32]. Morphologically, some cases of PTCL-F can show many morphological features of AITCL, including focal regressed follicles, high-endothelial venule hyperplasia, and focal follicular dendritic cell expansion [30].…”