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 Blood, 29 January 2009, Vol. 113, No. 5, pp. 1053-1061.
Prepublished online as a Blood First Edition Paper on October 31, 2008; DOI 10.1182/blood-2008-07-168682.

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Submitted July 16, 2008
Accepted September 29, 2008

A distinctive subtype of t(14;18) negative nodal follicular non-Hodgkin lymphoma characterized by a predominantly diffuse growth pattern and deletions in the chromosomal region 1p36

Tiemo Katzenberger, Jorg Kalla, Ellen Leich, Heike Stocklein, Elena Hartmann, Sandra Barnickel, Swen Wessendorf, M. Michaela Ott, Hans Konrad Muller-Hermelink, Andreas Rosenwald, and German Ott*

Department of Pathology, University of Wuerzburg, Wuerzburg, Germany
Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany
Clinic for Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Department of Pathology, Caritas-Krankenhaus, Bad Mergentheim, Germany

* Corresponding author; email: german.ott{at}rbk.de.

Follicular lymphoma is a morphologically and genetically well characterized B-cell non-Hodgkin lymphoma that can show predominantly follicular, combined follicular and diffuse, or predominantly diffuse growth patterns. While approximately 85% of FL harbor the translocation t(14;18)(q32;q21) and consistently display a follicular growth pattern, predominantly diffuse FL are less well characterized on the phenotypical, molecular and clinical level. We studied 35 predominantly diffuse FL by immunohistochemistry, classical chromosome banding analysis, fluorescence in situ hybridization (FISH) and gene expression profiling. 28 of 29 analyzable cases lacked the t(14;18) and 27 of 29 cases revealed a unifying chromosomal aberration, a deletion in 1p36. Morphologically, 12 FL were grade 1 and 23 were grade 2, and the immunophenotype with frequent expression of CD10, BCL6 and CD23 was in line with a germinal center B-cell phenotype. The gene expression profiles of four predominantly diffuse FL fell into the spectrum of typical FL, with a unique enrichment of specific gene signatures. Remarkably, patients with diffuse FL frequently presented with low clinical stage and large, but localized inguinal tumors. These results suggest that predominantly diffuse FL represent a distinct subtype of t(14;18)-negative nodal FL with a unifying genetic alteration (deletion of 1p36) and characteristic clinical features.


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