Peripheral T-cell lymphomas of follicular helper T-cell type frequently display an aberrant CD3−/dimCD4+ population by flow cytometry: an important clue to the diagnosis of a Hodgkin lymphoma mimic

Abstract

Nodal follicular helper T-cell-derived lymphoproliferations (specifically the less common peripheral T-cell lymphomas of follicular type) exhibit a spectrum of histologic features that may mimic reactive hyperplasia or Hodgkin lymphoma. Even though angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma of follicular type share a common biologic origin from follicular helper T-cells and their morphology has been well characterized, flow cytometry of peripheral T-cell lymphomas of follicular type has not been widely discussed as a tool for identifying this reactive hyperplasia/Hodgkin lymphoma mimic. We identified 10 peripheral T-cell lymphomas of follicular type with available flow cytometry data from five different institutions, including two cases with peripheral blood evaluation. For comparison, we examined flow cytometry data for 8 classical Hodgkin lymphomas (including 1 lymphocyte-rich classical Hodgkin lymphoma), 15 nodular lymphocyte predominant Hodgkin lymphomas, 15 angioimmunoblastic T-cell lymphomas, and 26 reactive nodes. Lymph node histology and flow cytometry data were reviewed, specifically for the presence of a CD3 − /dim CD4 + aberrant T-cell population (described in angioimmunoblastic T-cell lymphomas), besides other T-cell aberrancies. Nine of 10 (90%) peripheral T-cell lymphomas of follicular type showed a CD3 − /dim CD4 + T-cell population constituting 29.3% (range 7.9-62%) of all lymphocytes. Five of 10 (50%) had nodular lymphocyte predominant Hodgkin lymphoma or lymphocyte-rich classical Hodgkin lymphoma-like morphology with scattered Hodgkin-like cells that expressed CD20, CD30, CD15, and MUM1. Three cases had a nodular growth pattern and three others exhibited a perifollicular growth pattern without Hodgkin-like cells. Epstein-Barr virus was positive in 1 of 10 cases (10%). PCR analysis showed clonal T-cell receptor gamma gene rearrangement in all 10 peripheral T-cell lymphomas of follicular type. By flow cytometry, 11 of 15 (73.3%) angioimmunoblastic T-cell lymphomas showed the CD3 − /dim CD4 + population (mean: 19.5%, range: 3-71.8%). Using a threshold of 3% for CD3 − /dim CD4 + T cells, all 15 nodular lymphocyte predominant Hodgkin lymphoma controls and 8 classical Hodgkin lymphomas were negative (Mann-Whitney P = 0.01, F-PTCL vs Hodgkin lymphomas), as were 25 of 26 reactive lymph nodes. The

Bright PD-1 expression by flow cytometry is a powerful tool for diagnosis and monitoring of angioimmunoblastic T-cell lymphoma

“…In tissue samples, we frequently encountered that other standard TFH markers were not informative by immunohistochemistry, or interpretation of immunohistochemistry was challenging. In our cohort, expression of other TFH markers was not observed by immunohistochemistry in seven cases (25% of cases; Case #3, 7,8,12,15,19,28). Additional three cases (11% of cases; Case #21, 22, 27) presented with concomitant lymphoid neoplasm, which obscured morphologic and immunohistochemical evaluation for AITL ( Fig.…”

“…Previous studies identified abnormal T-cell population with sCD3-/CD4+immunophenotype in AITL [9][10][11][12][13] . In our cohort,~15% of AITL show two distinct abnormal T-cell populations with and without surface CD3 expression (Case 10, 12, 17, 23).…”

Approach to nodal-based T-cell lymphomas

“…4). 24,48,52,53 A chromosomal translocation t(5;9)(q33;q22) involving ITK and SYK tyrosine kinases is found in about 20% of F-PTCL, and has been reported thus far in only one case of typical AITL. 48,54,55 The ITK-SYK fusion may be detected by fluorescence in situ hybridisation (FISH) assays, but its diagnostic value is rather limited.…”

Peripheral T-cell lymphoma mimicking classic Hodgkin’s lymphoma in a patient presenting with fevers of unknown origin

“…With Hodgkin’s lymphoma in particular, Gaulard et al first noted the utility of combining histology and immunohistochemistry to reveal a clonal T-cell population to distinguish the aforementioned entities 26. Further research has shown that the presence of an aberrant CD3(-dim) CD4(+) population by flow cytometry is displayed in PTCL of follicular helper type 27. Using said flow cytometry and clonal PCR can even help distinguish the rare entity of a Hodgkin’s lymphoma with expressing a T-cell antigen 28 29.…”