Micronodular thymoma: an epithelial tumour with abnormal chemokine expression setting the stage for lymphoma development.
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.
Ströbel
Philipp
P
Institute of Pathology, University of Würzburg, Germany. philipp.stroebel@mail.uni-wuerzburg.de
Marino
Mirella
M
Feuchtenberger
Martin
M
Rouzière
Anne-Sophie
AS
Tony
Hans Peter
HP
Wulbrand
Ulrich
U
Förster
Reinhold
R
Zettl
Andreas
A
Lee Harris
Nancy
N
Kreipe
Hans
H
Laeng
R Hubert
RH
Müller-Hermelink
Hans Konrad
HK
Marx
Alexander
A
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
D018925:Chemokines