title: PD-1 expression in T-cell lymphomas and reactive lymphoid entities: potential overlap in staining patterns between lymphoma and viral lymphadenitis.
abstract: Peripheral T-cell lymphomas are a heterogeneous group that often requires the use of ancillary testing for accurate diagnosis. This is particularly applicable to the diagnosis of angiommunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, unclassified (PTCLU), because of their histologic and immunophenotypic overlap with reactive lymphoid proliferations. Recently, immunohistochemistry for programmed death-1 (PD-1), a marker of follicular helper T cells, was shown to be sensitive in the detection of AITL and PTCLU. The sensitivity of this marker in reactive entities, however, has not been adequately evaluated. We confirm that PD-1 staining is a highly sensitive marker in the diagnosis of peripheral T-cell lymphomas: increased extrafollicular PD-1-positive cells were seen in 93% (76/82) of AITL, 62% (16/26) of PTCLU, and 11% (2/18) of anaplastic-lymphoma-kinase (ALK)-negative anaplastic large-cell lymphomas. The majority of reactive lymphadenopathies including Cat-scratch disease, Kikuchi lymphadenitis, Castleman disease, and reactive follicular hyperplasia showed no PD-1 staining outside follicles. Some reactive lymph nodes, showed increased extrafollicular PD-1-positive cells in a pattern similar to AITL and PTCLU, and include progressive transformation of germinal centers, viral lymphadenitis (Epstein-Barr virusand human immunodeficiency virus) and Rosai-Dorfman disease. This study shows that PD-1-positive cells may be increased in a number of settings other than T-cell lymphomas. We conclude that staining for PD-1 in reactive and atypical lymphadenopathies should be interpreted with caution and in the context of other ancillary immunophenotypic and molecular studies before a diagnosis of AITL or PTCLU is entertained.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Chandra
authors.initials: C
authors.lastname: Krishnan
authors.forename: Roger A
authors.initials: RA
authors.lastname: Warnke
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Arber
authors.forename: Yasodha
authors.initials: Y
authors.lastname: Natkunam
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002999:Clone Cells; D006801:Humans; D007119:Immunoblastic Lymphadenopathy / Q000175:diagnosis* / Q000378:metabolism; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008199:Lymphadenitis / Q000175:diagnosis* / Q000821:virology; D016411:Lymphoma, T-Cell, Peripheral / Q000175:diagnosis* / Q000378:metabolism; D011237:Predictive Value of Tests; D061026:Programmed Cell Death 1 Receptor
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor