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CD5-expressing B-cell non-Hodgkin's lymphomas with bcl-1 gene rearrangement
have a relatively homogeneous immunophenotype and are associated with an
overall poor prognosis
GH Segal, AS Masih, AC Fox, T Jorgensen, M Scott and RC Braylan
Department of Pathology, University of Florida College of Medicine,
Gainesville.
Mantle cell lymphomas (MCLs) are typically CD5-expressing B-cell non-
Hodgkin's lymphomas (NHLs) that frequently harbor the chromosomal
translocation 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 various
histologic and cytologic expressions, and in order to avoid using somewhat
arbitrary and subjective morphologic definitions, we chose to study cases
of MCL selected on more objective grounds. Specifically, 15 samples (from
14 patients) of CD5-expressing B-cell NHLs with detectable bcl-1 gene
rearrangement were included. Overall, these patients had relatively uniform
clinical manifestations. Most were older men (mean age, 67 years) who
presented with lymphadenopathy, high-stage disease, and bone marrow
involvement. All but two patients relapsed, demonstrated residual tumor, or
had disease progression after an initial response to various therapies.
Nine patients have died; these patients had a median survival of only 19
months. All cases could be classified within the broad morphologic spectrum
previously described for MCL, and no predominant histologic subtype was
observed. However, cases could be segregated into two major groups
according to tissue architecture: one with a purely diffuse pattern and the
other with at least a focal nodular component. Patients with purely diffuse
tumors had a lower survival 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 demonstrated intense CD20 expression, with typically
intense IgM and light chain expression, and relatively weak IgD expression.
In no case was CD10 detected on the neoplastic cells. DNA content analysis
showed aneuploidy only in three instances, and two groups of cases could be
arbitrarily defined on the basis of their S- phase fraction. A relationship
between a purely diffuse growth pattern and a high S-phase fraction
(greater than 5%) was observed. As expected from this association, patients
with tumors having high S-phase fractions fared worse (14% survival rate)
than those patients with tumors showing lower S-phase fractions (57%
survival rate). Thirteen NHLs from 12 patients had amplifiable 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 junctional sequences
and Ig joining region breakpoint sites.(ABSTRACT TRUNCATED AT 400 WORDS)
Volume 85,
Issue 6,
pp. 1570-1579,
03/15/1995
Copyright © 1995 by The American Society of Hematology
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