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

J Pathol. 2005 Sep;207(1):72-82. doi: 10.1002/path.1808.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Mediastinal Neoplasms / pathology
  • Middle Aged
  • Neoplasms, Second Primary / immunology*
  • Neoplasms, Second Primary / pathology
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets / immunology
  • Thymoma / immunology*
  • Thymoma / pathology
  • Thymus Gland / immunology
  • Thymus Neoplasms / immunology*
  • Thymus Neoplasms / pathology


  • Chemokines