IRTA1 is selectively expressed in nodal and extranodal marginal zone lymphomas.
OBJECTIVE
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.


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.
Institute of Haematology, University of Perugia, Ospedale S Maria della Misericordia, Perugia, Italy. faliniem@unipg.it
Brunangelo
B
Falini
Claudio
C
Agostinelli
Barbara
B
Bigerna
Alessandra
A
Pucciarini
Roberta
R
Pacini
Alessia
A
Tabarrini
Flavio
F
Falcinelli
Milena
M
Piccioli
Marco
M
Paulli
Marcello
M
Gambacorta
Maurilio
M
Ponzoni
Enrico
E
Tiacci
Stefano
S
Ascani
Maria Paola
MP
Martelli
Riccardo
R
Dalla Favera
Harald
H
Stein
Stefano A
SA
Pileri
D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D011961:Receptors, Fc / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014178:Translocation, Genetic
D014408:Biomarkers, Tumor; C423544:FCRL4 protein, human; D011961:Receptors, Fc