title: Peripheral T-cell lymphomas of follicular T-helper cell derivation with Hodgkin/Reed-Sternberg cells of B-cell lineage: both EBV-positive and EBV-negative variants exist.
abstract: Peripheral T-cell lymphomas (PTCLs) are functionally and morphologically complex. Epstein-Barr virus (EBV)-positive B cells have been reported in angioimmunoblastic T-cell lymphoma (AITL) and other PTCLs and may mimic Hodgkin/Reed-Sternberg (HRS) cells, but EBV-negative HRS-like B cells have not been described. We wished to assess the nature of the PTCL associated with HRS-like cells and to determine whether EBV-negative HRS-like cells may be seen. We identified 57 PTCL cases reported as containing HRS-like cells. These included 32 AITL, 19 PTCL, not otherwise specified (NOS), 3 PTCL-NOS, follicular variant, 1 PTCL-NOS, T-zone variant, and 2 adult T-cell leukemia/lymphoma cases. All patients were adults with a median age of 63 and presented with lymphadenopathy. The male:female ratio was 31:26 (1.2:1). Clonal TRG rearrangement was detected in 46/53 cases. Six of 38 cases had a concomitant clonal immunoglobulin gene rearrangement. In 52/57 cases the HRS cells were positive for EBV. Five cases, 3 classified as AITL and 2 as PTCL-NOS, follicular variant, contained HRS-like cells negative for EBV. All PTCLs with EBV-negative HRS cells had a T follicular helper cell immunophenotype. The neoplastic T cells expressed CD3, CD4, and PD-1 and formed rosettes around the HRS-like cells. The HRS-like cells were positive for CD20 (variable intensity), PAX5, CD30, and CD15 (4/5). We conclude that both EBV-positive and EBV-negative HRS-like B cells may occur in the background of PTCL; caution is needed to avoid misdiagnosis as classical Hodgkin lymphoma. The close interaction between the HRS-like cells and the rosetting PD-1-positive T cells suggests a possible pathogenetic role in this phenomenon and provides new insights into the abnormal B-cell proliferations that occur in the context of TFH malignancies.
authors.affiliation: Hematopathology Section §Molecular Diagnostics Unit, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. elainejaffe@nih.gov
authors.forename: Alina
authors.initials: A
authors.lastname: Nicolae
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Girish
authors.initials: G
authors.lastname: Venkataraman
authors.forename: Anahi
authors.initials: A
authors.lastname: Vijnovich-Baron
authors.forename: Liqiang
authors.initials: L
authors.lastname: Xi
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015139:Blotting, Southern; D020031:Epstein-Barr Virus Infections / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D016411:Lymphoma, T-Cell, Peripheral / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016539:Reed-Sternberg Cells / Q000473:pathology* / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000473:pathology*