CD5-EXPRESSING B-CELL NON-HODGKINS-LYMPHOMAS WITH BCL-1 GENE REARRANGEMENT HAVE A RELATIVELY HOMOGENEOUS IMMUNOPHENOTYPE AND ARE ASSOCIATEDWITH AN OVERALL POOR-PROGNOSIS

Mantle cell lymphomas (MCLs) are typically CD5-expressing B-cell non-H odgkin's lymphomas (NHLs) that frequently harbor the chromosomal trans location t(11;14) or bcl-1 gene rearrangements. Insufficient data are available on the biologic features and clinical behavior of rigorously characterized MCL. As these NHLs have been reported to exhibit variou s histologic and cytologic expressions, and in order to avoid using so mewhat arbitrary and subjective morphologic definitions, we chose to s tudy cases of MCL selected on more objective grounds. Specifically, 15 samples (from 14 patients) of CDS-expressing B-cell NHLs with detecta ble bcl-1 gene rearrangement were included. Overall, these patients ha d relatively uniform clinical manifestations. Most were older men (mea n age, 67 years) who presented with lymphadenopathy, high-stage diseas e, and bone marrow involvement. All but two patients relapsed, demonst rated residual tumor, or had disease progression after an initial resp onse to various therapies. Nine patients have died; these patients had a median survival of only 19 months. All cases could be classified wi thin the broad morphologic spectrum previously described for MCL, and no predominant histologic subtype was observed. However, cases could b e segregated into two major groups according to tissue architecture: o ne with a purely diffuse pattern and the other with at least a focal n odular component. Patients with purely diffuse tumors had a lower surv ival rate (0%) than those with tumors having a nodular component (62% survival rate). In contrast to the morphologic variability, these NHL exhibited a rather homogeneous immunophenotypic pattern. All cases dem onstrated intense CD20 expression, with typically intense IgM and ligh t chain expression, and relatively weak IgD expression. In no case was CD10 detected on the neoplastic cells. DNA content analysis showed an euploidy only in three instances, and two groups of cases could be arb itrarily defined on the basis of their S-phase fraction. A relationshi p between a purely diffuse growth pattern and a high S-phase fraction (greater than 5%) was observed. As expected from this association, pat ients with tumors having high S-phase fractions fared worse (14% survi val rate) than those patients with tumors showing lower S phase fracti ons (57% survival rate). Thirteen NHLs from 12 patients had amplifiabl e bcl-1 gene rearrangements at the major translocation cluster (MTC). The bcl-1 breakpoints aggregated within a 63-bp region of the MTC, and the amplified tumor DNA from each patient had unique N-nucleotide jun ctional sequences and lg joining region breakpoint sites. Two addition al NHLs had bcl-1 gene rearrangements detected only with Southern blot hybridization using a genomic probe directed at a breakpoint site dis tant from the MTC. We conclude that CD5-expressing B-cell NHLs with bc l-1 gene rearrangement can be morphologically classified as MCL, have relatively uniform immuno-phenotypic characteristics, and are associat ed with an overall poor prognosis. Architectural growth pattern and ki netic information, such as S-phase fraction, may help separate a more aggressive group of these NHL from a relatively less aggressive subset . (C) 1995 by The American Society of Hematology.