Micronodular thymoma: an epithelial tumour with abnormal chemokine expression setting the stage for lymphoma development.

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.

• Authors: Philipp Ströbel, Mirella Marino, Martin Feuchtenberger, Anne-Sophie Rouzière, Hans Peter Tony, Ulrich Wulbrand, Reinhold Förster, Andreas Zettl, Nancy Lee Harris, Hans Kreipe, R Hubert Laeng, Hans Konrad Müller-Hermelink, Alexander Marx
• Journal: The Journal of pathology (J Pathol) Vol. 207 Issue 1 Pg. 72-82 (Sep 2005) ISSN: 0022-3417 [Print] England
• PMID: 15965907 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Chemical References

• Chemokines

Topics

• Adult
• Aged
• Aged, 80 and over
• B-Lymphocyte Subsets (immunology)
• Chemokines (metabolism)
• Dendritic Cells (pathology)
• Epithelial Cells (pathology)
• Female
• Gene Rearrangement, B-Lymphocyte
• Humans
• Hyperplasia (immunology)
• Immunophenotyping
• In Situ Hybridization, Fluorescence
• Macrophages (pathology)
• Male
• Mediastinal Neoplasms (immunology, pathology)
• Middle Aged
• Neoplasms, Second Primary (immunology, pathology)
• Oligonucleotide Array Sequence Analysis
• Reverse Transcriptase Polymerase Chain Reaction
• T-Lymphocyte Subsets (immunology)
• Thymoma (immunology, pathology)
• Thymus Gland (immunology)
• Thymus Neoplasms (immunology, pathology)