Original ArticlesExpansion of PD1-positive T Cells in Nodal Marginal Zone Lymphoma A Potential Diagnostic PitfallEgan, Caoimhe MB, BCh, BAO*; Laurent, Camille MD, PhD†; Alejo, Julie C. BS*; Pileri, Stefano MD, PhD‡; Campo, Elias MD, PhD§; Swerdlow, Steven H. MD∥; Piris, Miguel MD, PhD¶; Chan, Wing C. MD#; Warnke, Roger MD**; Gascoyne, Randy D. MD††; Xi, Liqiang MD*; Raffeld, Mark MD*; Pittaluga, Stefania MD, PhD*; Jaffe, Elaine S. MD* Author Information *National Institutes of Health, Bethesda, MD †Toulouse Center of Research on Cancer-Oncopole, CHU Toulouse, CRCT Inserm U1037, Toulouse, France ‡European Institute of Oncology, IRCCS—Scientific Institute for Research, Hospitalization and Health Care, Milan, Italy §Hospital Clinic of Barcelona, University of Barcelona, Barcelona ¶Jiménez Díaz Foundation University Hospital, Madrid, Spain ∥Department of Pathology, University of Pittsburgh, Pittsburgh, PA #City of Hope Medical Center, Duarte **Department of Pathology, Stanford University, Stanford, CA ††British Columbia Cancer, Centre for Lymphoid Cancer, Vancouver, BC, Canada Conflicts of Interest and Source of Funding: Supported by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute. S.P. is supported by a grant (n. 21198) of the Italian Association for Cancer Research, Milan, Italy. The remaining authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Elaine S. Jaffe, MD, Center for Cancer Research, National Cancer Institute, Building 10, Room 3S235, Bethesda, MD 20892-1500 (e-mail: [email protected]). The American Journal of Surgical Pathology 44(5):p 657-664, May 2020. | DOI: 10.1097/PAS.0000000000001414 Buy Metrics Abstract The diagnosis of nodal marginal zone lymphoma (NMZL) can be challenging, with the differential diagnosis including other low-grade B-cell lymphomas, reactive hyperplasia, and even some cases of peripheral T-cell lymphoma (PTCL). PTCL may have a perifollicular growth pattern mimicking NMZL. We and others have noted an atypical distribution of T-follicular helper (TFH) cells in some cases of NMZL. This study was prompted by the diagnosis of NMZL in several cases in which a marked increase of TFH cells, as determined by staining for programmed death-1 (PD1), had prompted suspicion for a diagnosis of PTCL. We analyzed PD1 staining in 48 cases of NMZL to characterize the extent and pattern of the PD1-positive infiltrate. Three main patterns of PD1 staining were identified: follicular pattern (peripheral, n=16; central, n=9; mixed, n=3), diffuse pattern (n=4), and a reduced or normal staining pattern in residual follicles (n=16). A comprehensive analysis of other TFH markers was undertaken in 14 cases with a high content of PD1-positive cells that were confirmed as B-cell lymphoma by clonality analysis. We describe in detail 5 of these cases in which PTCL was an initial consideration. This study illuminates the diverse immunohistochemical patterns encountered in NMZL and highlights a diagnostic pitfall important for diagnostic accuracy. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.