title: 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.affiliation: Institute of Pathology, University of Würzburg, Germany. philipp.stroebel@mail.uni-wuerzburg.de
authors.forename: Philipp
authors.initials: P
authors.lastname: Ströbel
authors.forename: Mirella
authors.initials: M
authors.lastname: Marino
authors.forename: Martin
authors.initials: M
authors.lastname: Feuchtenberger
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Rouzière
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Tony
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wulbrand
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
authors.forename: Andreas
authors.initials: A
authors.lastname: Zettl
authors.forename: Nancy
authors.initials: N
authors.lastname: Lee Harris
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
authors.forename: R Hubert
authors.initials: RH
authors.lastname: Laeng
authors.forename: Hans Konrad
authors.initials: HK
authors.lastname: Müller-Hermelink
authors.forename: Alexander
authors.initials: A
authors.lastname: Marx
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016175:B-Lymphocyte Subsets / Q000276:immunology; D018925:Chemokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000473:pathology; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D006965:Hyperplasia / Q000276:immunology; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008264:Macrophages / Q000473:pathology; D008297:Male; D008479:Mediastinal Neoplasms / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000276:immunology* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013945:Thymoma / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology; D013953:Thymus Neoplasms / Q000276:immunology* / Q000473:pathology
chemical_list: D018925:Chemokines