Peripheral T-cell lymphomas of follicular helper T-cell type frequently display an aberrant CD3(-/dim)CD4(+) population by flow cytometry: an important clue to the diagnosis of a Hodgkin lymphoma mimic.
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 high frequency of CD3(-/dim)CD4(+) aberrant T cells is similar in angioimmunoblastic T-cell lymphomas and peripheral T-cell lymphomas of follicular type, and is a useful feature in distinguishing peripheral T-cell lymphomas of follicular type from morphologic mimics such as reactive hyperplasia or Hodgkin lymphoma.
Department of Pathology, University of Chicago, Chicago, IL, USA.
Mir
M
Alikhan
Department of Pathology, City of Hope Medical Center, Duarte, CA, USA.
Joo Y
JY
Song
Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Aliyah R
AR
Sohani
Department of Pathology, University of Paris-Est, Hôpital Henri Mondor, Créteil, France.
Julien
J
Moroch
Department of Immunology, University of Paris-Est, Hôpital Henri Mondor, Créteil, France.
Anne
A
Plonquet
Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Amy S
AS
Duffield
Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
Michael J
MJ
Borowitz
Department of Pathology, Mayo Clinic, Jacksonville, FL, USA.
Liuyan
L
Jiang
Department of Pathology, MD Anderson, Houston, TX, USA.
Carlos
C
Bueso-Ramos
Department of Pathology, Henry Ford Health systems, Detroit, MI, USA.
Kedar
K
Inamdar
Department of Pathology, Henry Ford Health systems, Detroit, MI, USA.
Madhu P
MP
Menon
Department of Pathology, University of Chicago, Chicago, IL, USA.
Sandeep
S
Gurbuxani
Department of Pathology, University of Chicago, Chicago, IL, USA.
Ernest
E
Chan
Department of Hematology/Oncology, University of Chicago, Chicago, IL, USA.
Sonali M
SM
Smith
National Cancer Institute, Section of Hematopathology, National Institutes of Health, Bethesda, MD, USA.
Alina
A
Nicolae
National Cancer Institute, Section of Hematopathology, National Institutes of Health, Bethesda, MD, USA.
Elaine S
ES
Jaffe
Department of Pathology, University of Paris-Est, Hôpital Henri Mondor, Créteil, France.
Philippe
P
Gaulard
Department of Pathology, University of Chicago, Chicago, IL, USA.
Girish
G
Venkataraman
D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003937:Diagnosis, Differential; D005260:Female; D005434:Flow Cytometry; D006689:Hodgkin Disease / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D016411:Lymphoma, T-Cell, Peripheral / Q000175:diagnosis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology*