Preferential Dissemination of B-Cell Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma to the Splenic Marginal Zone

Author:

Du Ming-Qing1,Peng Huai-Zheng1,Dogan Ahmet1,Diss Tim C.1,Liu Haiqun1,Pan Lang-Xing1,Moseley Robin P.1,Briskin Michael J.1,Chan John K.C.1,Isaacson Peter G.1

Affiliation:

1. From the Department of Histopathology and the Department of Medicine, University College London Medical School, London, UK; LeukoSite, Inc, Cambridge, MA; and the Department of Pathology, Queen Elizabeth Hospital, Hong Kong.

Abstract

Abstract The tendency for gastric mucosa-associated lymphoid tissue (MALT) lymphoma cells preferentially to localize around reactive B-cell follicles, both in the mucosa and regional lymph nodes, coupled with their immunophenotype, has led to the proposal that the normal cell counterpart of this lymphoma is the marginal zone B cell. In keeping with this proposition, lymphocytes expressing the lymphoma idiotype have been detected in the splenic marginal zone in a single case of gastric MALT lymphoma. To confirm that this truly represented preferential homing of MALT lymphoma to the splenic marginal zone, we have now re-examined this case, together with 17 other cases, using both immunohistochemical and molecular methods in an attempt to establish clonal identity between the gastric lymphoma and cells in the splenic marginal zone. In three cases, the spleen was characterized by marked expansion of marginal zones by cells showing the same pattern of Ig light chain restriction as the gastric lymphoma. None of the remaining 15 cases showed histologic evidence of lymphomatous infiltration. Analysis of the Ig genes by polymerase chain reaction (PCR), cloning, and sequencing confirmed clonal identity between the splenic marginal zone infiltrates and the gastric lymphoma in the histologically involved cases. Amplifiable DNA could be extracted from only 5 of the remaining 15 cases. In 3 of these cases, including the case previously studied using an anti-idiotype, involvement of the splenic marginal zone could be confirmed using microdissection and clone-specific PCR. No involvement could be detected in the remaining 2 cases. In addition, we have shown that mucosal addressin cell adhesion molecule-1 (MAdCAM-1), the primary homing receptor of gut-mucosa for lymphocytes, was strongly expressed by the sinus lining cells of the splenic marginal zone. These results provide strong evidence for preferential involvement of the marginal zone when gastric MALT lymphomas disseminate to the spleen, which is in keeping with the notion that the marginal zone B cells are the normal counterparts of MALT lymphoma cells.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference32 articles.

1. Malignant lymphoma of mucosa-associated lymphoid tissue.;Isaacson;Histopathology,1987

2. Analysis of mutations in immunoglobulin heavy chain variable region genes of microdissected marginal zone (MGZ) B cells suggests that the MGZ of human spleen is a reservoir of memory B cells.;Dunn;J Exp Med,1995

3. Ongoing mutation in MALT lymphoma immunoglobulin VH gene suggests that antigen stimulation plays a role in the clonal expansion.;Du MQ;Leukemia,1996

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