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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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LYMPHOID NEOPLASIA

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 Katzenberger1, Jörg Kalla1, Ellen Leich1, Heike Stöcklein1,2, Elena Hartmann1, Sandra Barnickel1, Swen Wessendorf3, M. Michaela Ott4, Hans Konrad Müller-Hermelink1, Andreas Rosenwald1,*, and German Ott1,2,*

1 Department of Pathology, University of Würzburg, Würzburg; 2 Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart; 3 Clinic for Internal Medicine III, University Hospital of Ulm, Ulm; and 4 Department of Pathology, Caritas-Krankenhaus, Bad Mergentheim, Germany

Follicular lymphoma (FL) 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. Although approximately 85% of FLs harbor the translocation t(14;18)(q32;q21) and consistently display a follicular growth pattern, predominantly diffuse FLs 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. A total of 28 of 29 analyzable cases lacked t(14;18), and 27 of 29 cases revealed a unifying chromosomal aberration, a deletion in 1p36. Morphologically, 12 FLs 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 4 predominantly diffuse FLs 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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