Premium
Micronodular thymoma: an epithelial tumour with abnormal chemokine expression setting the stage for lymphoma development
Author(s) -
Ströbel Philipp,
Marino Mirella,
Feuchtenberger Martin,
Rouzière AnneSophie,
Tony Hans Peter,
Wulbrand Ulrich,
Förster Reinhold,
Zettl Andreas,
Lee Harris Nancy,
Kreipe Hans,
Laeng R Hubert,
MüllerHermelink Hans Konrad,
Marx Alexander
Publication year - 2005
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1808
Subject(s) - thymoma , cxcl13 , lymphoma , pathology , biology , chemokine , b cell , malt lymphoma , monoclonal , germinal center , ccl20 , cancer research , immunology , monoclonal antibody , medicine , immune system , chemokine receptor , antibody
Abstract The aetiology of primary B‐cell lymphomas of the thymus is enigmatic. Although thymic follicular lymphoid hyperplasia (TFH) is commonly associated with myasthenia gravis (MG), lymphoma is not a complication of this condition. The present paper reports a high frequency of monoclonal B‐cell populations (6 of 18 cases; 33%) in micronodular thymoma (MNT), a peculiar thymic epithelial neoplasm with a B‐cell‐rich stroma, while B cells were consistently polyclonal in TFH (25 cases) and other types of thymomas (15 cases) ( p < 0.001). An intratumoural lymphoma could be identified in three of the six monoclonal MNTs. Sequencing of the monoclonal IgH chain revealed partially overlapping VDJ gene usage in MNT and thymic mucosa‐associated lymphoid tissue (MALT) lymphomas. The neoplastic epithelium of MNTs, but not of TFH and other types of thymoma, expressed high levels of dendritic cell, T‐cell, and B‐cell chemoattractants, such as CCL18, CCR6, and CCL20. It is concluded that abnormal chemokine expression in an epithelial tumour, MNT, can promote the recruitment of MALT, the emergence of monoclonal B cells, and, eventually, the subsequent development of mediastinal lymphomas. More generally, the concept that expression of a ‘high‐risk’ spectrum of chemokines due to local or genetic factors may interfere with B‐cell homeostasis and may contribute to MALT lymphoma development in chronic inflammatory states is proposed. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.