Expansion of PD1-positive T Cells in Nodal Marginal Zone Lymphoma: A Potential Diagnostic Pitfall

Caoimhe Egan, Camille Laurent, Julie C Alejo, Stefano Pileri, Elias Campo, Steven H Swerdlow, Miguel Piris, Wing C Chan, Roger Warnke, Randy D Gascoyne, Liqiang Xi, Mark Raffeld, Stefania Pittaluga, Elaine S Jaffe

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)657-664
Number of pages8
JournalAmerican Journal of Surgical Pathology
Issue number5
Publication statusPublished - May 2020


  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor/analysis
  • Cell Proliferation
  • Diagnosis, Differential
  • Diagnostic Errors
  • Europe
  • Female
  • Humans
  • Lymphoma, B-Cell, Marginal Zone/immunology
  • Lymphoma, T-Cell, Peripheral/immunology
  • Male
  • Middle Aged
  • North America
  • Predictive Value of Tests
  • Programmed Cell Death 1 Receptor/analysis
  • T-Lymphocytes, Helper-Inducer/immunology
  • Tumor Microenvironment


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