Published online 16 July 2009
Haematologica, Vol 94, Issue 11, 1595-1598 doi:10.3324/haematol.2009.010173
Copyright © 2009 by Ferrata Storti Foundation
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Malignant Lymphomas

Differential diagnosis of cyclin D2+ mantle cell lymphoma based on fluorescence in situ hybridization and quantitative real-time-PCR

Leticia Quintanilla-Martinez1, Julia Slotta-Huspenina2, Ina Koch2, Margit Klier1, Eric D. Hsi3, Laurence de Leval4, Wolfram Klapper5, Stefan Gesk6, Reiner Siebert6, Falko Fend1

1 Institute of Pathology, Eberhard-Karls-University of Tübingen, Tübingen, Germany
2 Institute of Pathology, Technical University Munich, Munich Germany
3 Department of Clinical Pathology, Hematopathology Section, Cleveland Clinic, Cleveland, USA
4 Department of Pathology, CHU Sart Tilman, University of Liege, Liege, Belgium
5 Institutes of Pathology
6 Human Genetics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Campus Kiel, Germany

Correspondence: Leticia Quintanilla-Martinez, M.D., Eberhard-Karls-University of Tübingen, Institute of Pathology, Liebermeisterstrasse 8, 72076 Tübingen, Germany. E-mail:leticia.quintanilla-fend{at}med.uni-tuebingen.de

Mantle cell lymphoma is characterized by the t(11;14) chromosomal translocation, resulting in the overexpression of cyclin D1 (CycD1). Recently, cases of mantle cell lymphoma negative for cycD1 but positive for cycD2 or cycD3 were identified by gene expression profiling and confirmed by immunohistochemistry. We analyzed 4 cases of cycD2+ mantle cell lymphoma with a translocation involving the CCND2 locus, and its differential diagnosis from 35 mature B-cell non-Hodgkin’s lymphomas based on immunohistochemistry, quantitative RT-PCR and FISH analysis. Bona fide cycD2+ mantle cell lymphoma carried translocations involving the CCND2 gene, and IGH and IGK loci were identified as partners. As a result of this translocation, cycD2 mRNA was highly over-expressed when compared with normal lymphoid tissue and other B-cell non-Hodgkin’s lymphomas, including chronic lymphocytic leukemia, making this technique ideally suited to identify cycD2+mantle cell lymphoma. In contrast, positive immunostaining for cycD2 was found in most B-cell non-Hodgkin’s lymphomas, and therefore, it is not specific for a diagnosis of cycD2+mantle cell lymphoma.

Key words: cyclin D2+, mantle cell lymphoma (MCL), FISH, QRT-PCR.


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S. A. Pileri and B. Falini
Mantle cell lymphoma
Haematologica, November 1, 2009; 94(11): 1488 - 1492.
[Full Text] [PDF]