IRTA1 is selectively expressed in nodal and extranodal marginal zone lymphomas

Histopathology. 2012 Nov;61(5):930-41. doi: 10.1111/j.1365-2559.2012.04289.x. Epub 2012 Jun 20.

Abstract

Aims: The aim of this study was to search for a molecule selectively expressed by marginal zone (MZ) lymphomas (MZLs), whose diagnosis is currently based on morphological criteria and negativity for markers detectable in other B-cell lymphomas.

Methods and results: Two thousand one hundred and four peripheral lymphomas of various types were immunostained with a monoclonal antibody against immunoglobulin superfamily receptor translocation-associated 1 (IRTA1), which recognizes the equivalents of MZ in human lymphoid tissues other than spleen. IRTA1 expression was restricted to extranodal (93%) and nodal MZLs (73%) and to lymphomas with MZ differentiation. Extranodal MZL cells with the strongest IRTA1 expression were usually located adjacent to epithelia, mimicking the IRTA1 expression pattern of normal and acquired mucosa-associated lymphoid tissue (MALT). The cytological features, growth pattern and IRTA1 positivity in nodal MZLs suggest they may derive from IRTA1(+) perifollicular B cells or monocytoid B cells detectable in reactive lymph nodes. Double immunostaining for IRTA1/bcl-6 tracked the colonization of B-cell follicles by MZL cells, and showed modulation of their phenotype (e.g. acquisition of bcl-6) during recirculation through germinal centres. MZL cells differentiating into plasma cells usually lost IRTA1.

Conclusions: These results further expand our knowledge of the biology of MZLs, and highlight IRTA1 as the first positive marker for MZLs, enabling more accurate diagnosis of these neoplasms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Biomarkers, Tumor / immunology
  • Biomarkers, Tumor / metabolism
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell, Marginal Zone / genetics
  • Lymphoma, B-Cell, Marginal Zone / immunology*
  • Lymphoma, B-Cell, Marginal Zone / pathology*
  • Receptors, Fc / metabolism*
  • Spleen / immunology
  • Spleen / pathology
  • Translocation, Genetic

Substances

  • Biomarkers, Tumor
  • FCRL4 protein, human
  • Receptors, Fc