Micronodular thymoma

An epithelial tumour with abnormal chemokine expression setting the stage for lymphoma development

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

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)72-82
Number of pages11
JournalJournal of Pathology
Volume207
Issue number1
DOIs
Publication statusPublished - Sep 2005

Fingerprint

Thymoma
Chemokines
Lymphoma
B-Lymphocytes
Hyperplasia
Marginal Zone B-Cell Lymphoma
Neoplasms
Overlapping Genes
Thymus Neoplasms
Glandular and Epithelial Neoplasms
Myasthenia Gravis
Chemotactic Factors
B-Cell Lymphoma
Lymphoid Tissue
Dendritic Cells
Thymus Gland
Mucous Membrane
Homeostasis
Epithelium
T-Lymphocytes

Keywords

  • B cell
  • Chemokine
  • Lymphoma
  • MALT
  • Mediastinal
  • Micronodular
  • Thymoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Micronodular thymoma : An epithelial tumour with abnormal chemokine expression setting the stage for lymphoma development. / Ströbel, Philipp; Marino, Mirella; Feuchtenberger, Martin; Rouzière, Anne Sophie; Tony, Hans Peter; Wulbrand, Ulrich; Förster, Reinhold; Zettl, Andreas; Harris, Nancy Lee; Kreipe, Hans; Laeng, R. Hubert; Müller-Hermelink, Hans Konrad; Marx, Alexander.

In: Journal of Pathology, Vol. 207, No. 1, 09.2005, p. 72-82.

Research output: Contribution to journalArticle

Ströbel, P, Marino, M, Feuchtenberger, M, Rouzière, AS, Tony, HP, Wulbrand, U, Förster, R, Zettl, A, Harris, NL, Kreipe, H, Laeng, RH, Müller-Hermelink, HK & Marx, A 2005, 'Micronodular thymoma: An epithelial tumour with abnormal chemokine expression setting the stage for lymphoma development', Journal of Pathology, vol. 207, no. 1, pp. 72-82. https://doi.org/10.1002/path.1808
Ströbel, Philipp ; Marino, Mirella ; Feuchtenberger, Martin ; Rouzière, Anne Sophie ; Tony, Hans Peter ; Wulbrand, Ulrich ; Förster, Reinhold ; Zettl, Andreas ; Harris, Nancy Lee ; Kreipe, Hans ; Laeng, R. Hubert ; Müller-Hermelink, Hans Konrad ; Marx, Alexander. / Micronodular thymoma : An epithelial tumour with abnormal chemokine expression setting the stage for lymphoma development. In: Journal of Pathology. 2005 ; Vol. 207, No. 1. pp. 72-82.
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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.",
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