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 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 6 (March 15), 2000:
pp. 1950-1956
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Non-MALT marginal zone B-cell lymphomas: a description of clinical
presentation and outcome in 124 patients
Françoise Berger,
Pascale Felman,
Catherine Thieblemont,
Thierry Pradier,
Lucille Baseggio,
Paul-Andre Bryon,
Gilles Salles,
Evelyne Callet-Bauchu, and
Bertrand Coiffier
From the Service d'Anatomie Pathologique and Laboratoire
d'Hèmatologie, Hùpital Edouard-Herriot, Lyon, France;
Laboratoire d'Hèmatologie, Service d'Hèmatologie, and
Service de Chirurgie Gènèrale, Centre Hospitalier Lyon-Sud,
Pierre Bènite, France.
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Abstract |
Marginal zone B-cell lymphoma (MZL) is a recently individualized
lymphoma that encompasses mucosa-associated lymphoid tissue (MALT)
lymphoma, splenic lymphoma with or without villous lymphocytes, and
nodal lymphoma with or without monocytoid B-cells. If the clinical
description and outcome of MALT lymphoma is well known, this is not the
case for the other subtypes. We reviewed 124 patients presenting
non-MALT MZL treated in our department to describe the morphologic and
clinical presentation and the outcome of these lymphomas. Four clinical
subtypes were observed: splenic, 59 patients; nodal, 37 patients;
disseminated (splenic and nodal), 20 patients; and leukemic (not
splenic nor nodal), 8 patients. These lymphomas were usually CD5-,
CD10-, CD23-, and CD43-, but the detection of one or, rarely, two of
these antigens may be observed. Bone marrow and blood infiltrations
were frequent, except in the nodal subtype, but these locations were
not associated with a poorer outcome. Splenic and leukemic subtypes
were associated with a median time to progression (TTP) longer than 5 years, even in the absence of treatment or of complete response to
therapy. Nodal and disseminated subtypes were associated with a median
TTP of 1 year. However, in all these subtypes, survival was good with a
median survival of 9 years, allowing these lymphomas to be classified as indolent. Because of the retrospective nature of this analysis, no
conclusion may be drawn on the therapeutic aspects, but conservative treatments seem recommended for leukemic and splenic subtypes.
(Blood. 2000;95:1950-1956)
© 2000 by The American Society of Hematology.
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Introduction |
Among the new entities listed in the Revised
European-American Lymphoma (REAL) classification from the International
Lymphoma Study Group,1 most of the marginal zone
B-cell lymphomas (MZL) were categorized as a provisional entity,
including splenic lymphoma and nodal monocytoid B-cell lymphoma, but
not mucosa-associated lymphoid tissue (MALT) lymphoma that was
recognized and accepted years before.2 Even if the
forthcoming World Heath Organization (WHO) classification of neoplastic
diseases of the hematopoietic and lymphoid systems will consider them
as full-individualized lymphomas,3,4 some pathologists have
difficulties in recognizing them and in considering them as a true
entity. In the WHO classification, MZL is described with three
subtypes: extranodal MALT lymphoma,2,5 splenic MZL
with/without villous lymphocytes,6,7 and nodal MZL
with/without monocytoid B-cells.8,9 If these B-cell
lymphomas have only recently been recognized, they were previously
diagnosed under the names of other subtypes in the Working
Formulation10 or the Kiel classification.11 In
our preceding review of nonfollicular small-cell
lymphomas,12 the non-MALT MZL lymphomas were classified among the lymphoplasmacytoid lymphomas, but some cases may be found in
nearly all the other subtypes.13
The MZL term came from the supposed but controversial common origin of
the lymphoma cells with possibly different mechanisms of lymphoma
triggering. These lymphomas involve the marginal B-cell compartment of
lymphoid tissue outside the follicle mantle zone with a peculiar growth
pattern reminiscent of the marginal zone. They may also secondarily
involve the normal germinal centers, a pattern described as follicular
colonization.14 The cellular composition of these lymphomas
shows considerable variations: mostly clear cells with a
relatively abundant pale cytoplasm called monocytoid B cells or
centrocytic-like cells with a small percentage of larger cells and
plasmacytic cells. These cells have a virtually identical
immunophenotype, with the presence of surface immunoglobulin (Ig),
mainly IgM subtype, presence of B-cell markers (CD19+, CD20+, CD22+),
and absence of CD5, CD10, and CD23 antigens. There is no rearrangement
of bcl-1 or bcl-2 loci, but common cytogenetic abnormalities have been described, such as trisomy 3, trisomy X,
trisomy 18, or translocation (1;14).15-17
If the clinical characteristics and outcome of patients with MALT
lymphoma have been very well described,18,19 some
interrogations persist concerning the clinical characteristics,
prognostic parameters, and outcome of patients with non-MALT MZL. To
determine the clinical presentation and natural history of these
patients, we reviewed all our cases of MZL. We present here the
description of these patients with four different groups of patients,
according to their main sites of involvement.
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Patients and methods |
Patients
Between October 1987 and July 1998, 2152 lymphoma patients were
treated in our department, and 281 of these patients had a MZL with 157 of them having a MALT lymphoma. Patients with an extranodal location of
the lymphoma and either splenic, nodal, or bone marrow localizations
were deemed to have a disseminated MALT lymphoma, and they were not
included in this analysis.20 Thus, 124 cases of MZL were
included in this analysis. All of them have been reviewed and confirmed
by two of us (FB and PF) on morphologic aspect and immunophenotype. To
be included in this analysis, a patient must fulfill the histological
characteristics defined in the REAL classification1 and the
proposed WHO classification.4,21
We planned to group patients according to the two identified categories
in the REAL and WHO classifications, splenic and nodal MZL,4,7,9 but we rapidly found that some patients had both splenic and nodal involvement, thus the creation of the disseminated subtype. Finally, some patients did not have any of these localizations but only bone marrow and blood involvement, thus the creation of the
leukemic subtype. Four clinical subtypes were defined, depending on the
involved sites at diagnosis (Table 1): 59 (48%) patients had a spleen enlargement without peripheral lymph nodes (splenic subtype); 37 (30%) patients had enlarged peripheral lymph nodes without splenomegaly (nodal subtype); 20 (16%) patients had a
disseminated disease with splenomegaly and peripheral lymph nodes
(disseminated subtype); and 8 (6%) patients had bone marrow involvement without splenomegaly or peripheral lymph node (leukemic subtype).
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Table 1.
Initial clinical, morphologic, and biologic
characteristics of the 124 patients with MZL included in this
analysis
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Morphologic features and immunophenotype
The available pathologic and cytological specimens were reviewed
without knowledge of the clinical course and patients' outcome. All
slides obtained at diagnosis and from subsequent biopsies performed
during relapse or progression, whether they originated from nodal,
spleen, bone marrow, or blood locations, were reviewed by histological,
cytological, and immunologic methods. Immunologic characterization was
performed on paraffin sections in 70% of the cases, on frozen sections
and/or cell suspensions in 73% using a flow cytometer. CD5, CD10,
CD23, and CD43 were prospectively evaluated on CD19+ cells by double staining.
The histological pattern of infiltration in lymph nodes was peri- or
interfollicular (Figure 1A), sometimes
perisinusoidal or nodular (Figure 1B), and rarely follicular by
colonization of germinal centers. In the spleen, it was either a
perifollicular infiltration, surrounding the residual white pulp
follicles, with more than a marginal-zone aspect (Figure 1C), or a
nodular infiltration by colonization of white pulp and involvement of
red pulp associated with a diffuse invasion of the sinuses (Figure 1D);
rarely, it was an exclusive diffuse infiltration of congestive red pulp
with normal or atrophic white pulp. This last aspect was mostly
observed in splenic MZL with villous lymphocytes. In bone marrow, the
aspect was variable with paratrabecular, nodular, or interstitial
infiltration, sometimes limited to intrasinusoidal infiltration (mostly
in splenic MZL with villous lymphocytes). Cytological aspects were very
heterogeneous with several cell types usually associated in varying
proportions: cells resembling small round lymphocytes, small cells with
irregular nuclei (centrocyte-like cells), small cells with more regular nuclei and clear cytoplasm (monocytoid B-cells), small cells with plasmacytoid differentiation (Figure 1 B), plasma cells, and variable content of medium to large cells (centroblast- or immunoblast-like cells). In typical splenic white pulp involvement, central small round
cells were surrounded by medium cells with clear cytoplasm, interspersed with variable numbers of large cells. In peripheral blood,
splenic lymphoma with villous lymphocyte (SLVL) was defined by the
presence of at least 20% of typical villous lymphocytes, showing a
clumped chromatin and a basophilic cytoplasm with polar projections. In
contrast to the usual homogeneous picture of SLVL, the cytological
spectrum of other MZL varied from slightly atypical lymphoid cells,
sometimes looking like chronic lymphocytic leukemia cells, to
heterogeneous lymphoid populations, composed of plasmacytoid cells,
prolymphocytes, centrocyte-like cells, villous lymphocytes (always
<20%), and large atypical cells (sometimes with a prominent single
nucleolus) in varying numbers. It is of note that villous lymphocytes
were generally not typical, with shorter and thinner projections than
in SLVL, and that circulating monocytoid B cells were rarely observed.
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| Fig 1.
Marginal zone B-cell lymphoma.
(A) Nodal peri- and interfollicular infiltration by monocytoid B-cells
with clear cytoplasm (HE × 60). (B) Nodal perisinusoidal
infiltration by small tumoral B-cells with plasmacytic differentiation
(HE × 400). (C) Splenic perifollicular infiltration surrounding
the residual white pulp follicles, with typical "marginal-zone"
pattern (HE × 60). (D) Splenic nodular infiltration with
colonization of the white pulp by the tumoral cells associated with a
diffuse invasion of the sinuses in the red pulp (HE × 60).
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Patients were split into three subgroups according to morphologic
features: common MZL (78 patients, 63%) without circulating villous
lymphocytes and with less than 50% large cells, splenic MZL with
circulating villous lymphocytes (SLVL, 12 patients, 10%),5 and large cell-rich variant in cases with more than 50% of large cells
or sheets of large B-cells (34 patients, 27%). These last cases may be
considered as having a "transformed" lymphoma at diagnosis
because these criteria were those retained to define transformation in
relapsing patients or a composite lymphoma with MZL aspect and features
of diffuse large B-cell lymphoma. Usually, large-cell proliferation was
observed in lymph nodes and small-cell proliferation was observed in
bone marrow and blood.
Cytogenetic analyses
Cytogenetic studies were performed on peripheral blood, lymph nodes,
or spleen samples, as previously described.22 Chromosomal analyses were carried out on RHG-banded metaphases and
evaluated according to the ISCN (1995) recommendations.
Fluorescent in situ hybridization experiments were performed, using a
panel of probes (paints, centromeric, and telomeric probes) specific
for chromosomes X, 1, 3, 7, 8, 12, and 18.
Staging procedure
Initial staging procedures included complete physical examination,
thorax and abdominal computerized tomography, endoscopic examinations
in case of gastrointestinal symptoms, bone marrow biopsy, and dosage of
blood levels of lactic dehydrogenase (LDH),  2-microglobulin, and
serum albumin. Patients were staged according to the Ann Arbor system.
Treatment
This was not a prospective study. Thus, patients were treated
according to disease stage and disease location with the therapeutic options in usage at the time of diagnosis. Table
2 presents the initial treatment for the
different clinical subtypes. No pattern was observed during this time
period, but usually elderly patients were not initially treated except
in cases of clinically aggressive disease; patients with large
splenomegaly had a splenectomy, alone or followed by chlorambucil;
disseminated lymphoma patients were treated with chemotherapy, either
single agent (chlorambucil or fludarabine) or multidrug regimens (CHOP
combining cyclophosphamide, doxorubicin, vincristine, and prednisone),
CHOP-like regimens, or high-dose CHOP (ACVB regimen23).
Only 40% of the patients were treated with CHOP or high-dose CHOP
regimens, usually because of disseminated disease with adverse
prognostic factors or a high percentage of large cells. Therapeutic
options were very heterogeneous because diagnosis of MZL was often not
originally done in ancient cases.
Statistical analyses
Overall survival was defined as the time from diagnosis (first
biopsy) to death or last follow-up. Time-to-progression (TTP) survival
was defined as the time from onset of treatment to the date of first
progression or last follow-up. For patients who did not receive any
specific therapy, TTP was defined as the date of the decision not to
treat this patient to first progression or last follow-up. Complete
remission (CR) was defined as the disappearance of all clinical
evidence of the lymphoma. Partial response was defined as a >50%
regression of lymphoma masses. Survival was analyzed according to the
method of Kaplan and Meier.24 Differences between survival
curves were evaluated with the log-rank test.25
Multivariate analyses were performed, using a Cox stepwise proportional
hazard model to identify factors that might be of independent
significance influencing survival.26 Patient
characteristics analyzed for possibly influencing survival were
histological subtype, sex, age, performance status, presence of B
symptoms, stage, peripheral and thoracic or abdominal lymph node
enlargement, bone marrow involvement, spleen involvement, initial
localizations, number of extranodal sites, tumor bulkiness (>10 cm),
anemia defined as hemoglobin level <12 g/dl, serum albumin <35 g/L,
LDH level above normal value, or 2-microglobulin level >3 mg/L.
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Results |
The identification of three clinical subtypes, splenic, nodal, or
disseminated, was defined before the analysis because two of them were
described in the REAL classification and because we observed that some
patients had a disease too disseminated to enter into the other
definitions of the initial clinical picture. The leukemic cases were
defined secondarily because these cases did not fit into one of the
previous categories. Disseminated disease patients had splenic, nodal,
extranodal, and bone marrow involvement, and leukemic cases only had
bone marrow and blood locations as described in Table 1.
Morphological and immunologic aspects
There was a direct correlation between the clinical subtypes and the
three histological variants (Table 3).
Among the SLVL patients, all except one were of the splenic subtype.
The large cell-rich variant was more frequent in the nodal subtype but
was seen in 20% of the cases of splenic and disseminated subtypes.
MZL was described as a CD5-, CD23-, CD10-, and CD43-proliferation, but,
in spite of the classical morphologic aspect, we found some cases with
the presence of one or two of these antigens. Only two cases showed a
positive reaction for CD10 antigen but 15, 13, and 13 cases were
positive for CD5, CD23, and CD43 antigens, respectively. It is of note
that CD43 positivity when evaluated by flow cytometry was faint and/or
partial in most cases. Among them, five cases showed a double
positivity for CD5 and CD43 or CD10 and CD23 antigens. One case showed
a positivity for CD5, CD23, and CD43 antigens.
Cytogenetic abnormalities
Among these 124 patients, 56 had a cytogenetic analysis done, and 12 had a normal karyotype. Forty-four patients had one or several
cytogenetic abnormalities: addition or deletion of some part of any
chromosomes, trisomy, or translocations. In 16 cases, a
single cytogenetic abnormality existed, and, in 28 cases, multiple abnormalities were present. An abnormality of chromosome 1 was present
in 17 cases; of chromosome 3, mostly trisomy 3, in 17 cases; of
chromosome 11 in 2 cases; and of chromosome 18 in 14 cases. A
translocation that involved chromosome 1 was present in three cases,
chromosome 3 in four cases, chromosome 11 in nine cases, and chromosome
18 in two cases. The rearrangement of bcl-2 gene was observed in none
of these patients, but some patients having a translocation involving
chromosome 11 or chromosome 14 had a bcl-1 rearrangement
(manuscript in preparation).
Clinical presentation
Among the 124 cases, the sex ratio was 1:1 and median age was 60 years, which is not different from other lymphoma entities. However,
the median age was younger in the nodal subtype and older in the
leukemic subtype (.5 = 10.8, P < .05). By definition,
patients with splenic involvement were observed in the splenic and
disseminated subtypes, and patients with peripheral lymph nodes were
observed in the nodal and disseminated subtypes. Thoracic and/or
abdominal lymph nodes were present in 34%, 49%, and 55% of the
splenic, nodal, and disseminated subtypes, respectively. They were
absent in the leukemic subtype. Liver involvement was present in 26% of the cases, more frequently in splenic and disseminated subtypes (P = .06). Pleura involvement was present in 11% of the
cases, more often in disseminated subtypes (P < .001). Bone
marrow involvement was present in 72% of the cases, less frequently in
the nodal subtype (43% compared with 80%-100% in other subtypes,
P < .0001). Blood involvement was defined by the presence
of abnormal lymphocytes or a lymphocyte count more than
5 × 109/L. It was present in 43% of the cases but
was rare (11%) in nodal subtype, present in half of the cases with
splenic or disseminated subtypes, and nearly constant in the leukemic
subtype. The two patients without spleen or lymph node enlargement and
without blood involvement had a bone marrow examination because of
cytopenia. Only 14.5% of the patients had a localized disease, most of
them in the nodal subtype (Table 1). Only 21% of the patients had B
symptoms, and 18% had a poor performance status, most of them in the
disseminated subtype. A bulky tumor (>10 cm) was observed in 39.5%
of the patients, absent in leukemic subtype, and less frequent in nodal
subtype (P < .001). More than one extranodal site of
involvement was observed in 56% of the patients, less frequently in
nodal subtype (P < 001), these extranodal sites being bone
marrow and blood in the majority of the patients.
Forty-three percent of the patients had a high LDH level without
difference among the subtypes. A 2-microglobulin level above 3 mg/L
was observed in 59% of the patients, less frequently in nodal subtype
(P < .05. Anemia (hemoglobin level <12 g/dL) was observed
in 52% of the patients, mostly in splenic and disseminated subtypes
(P < .01). Thrombocytopenia was observed in 17% of the cases, essentially in splenic subtype. A low serum albumin level (<35
g/L) was observed in 25% of the patients, less frequently in nodal
subtype. At diagnosis, 19 (15%) patients had an M component, all in
blood and three in urine. This M component was an IgM in 15 cases, IgG
in 1 case, and IgA in 3 cases with an equal repartition for  and  chains. Median level of the M component was 8 g/L (1-51 g/L). Fourteen
(11%) patients had a positive Coombs test, 12 of them with anemia.
According to the International Prognostic Index,27 15% of
our patients had low risk, 33% low-intermediate risk, 33%
high-intermediate risk, and 19% high risk, but the repartition was
clearly different in the splenic, leukemic, nodal, or disseminated
subtypes, with nodal subtype patients having more of a lower risk and
disseminated subtype patients a higher risk (Table 1).
The differences observed in the clinical presentation between
histological variants are shown in Table 4.
Most of the observed differences are explained by the fact that SLVL
was mainly observed in the splenic subtype and large cell-rich variant
in the nodal and disseminated subtypes.
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Table 4.
Clinical, biologic, and immunologic characteristics of
the 124 MZL patients according to the morphologic variants
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TTP and survival
Median survival and TTP for the whole group of patients was 9.1 years and 3.8 years, respectively, (Figure
2) without any plateau and a nearly
constant event rate. Figures 3 and
4 show TTP and survival for the four
clinical subtypes. Median TTP was 6.9 years and 5.6 years in splenic
and leukemic subtypes compared with 1.3 years and 1.1 years in nodal
and disseminated subtypes, respectively. If TTP was slightly longer in
SLVL cases (not reached) and common (4 years) subtypes than in
large-cell subtype (3 years), this was not statistically different.
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| Fig 3.
Time to progression of the 124 patients with marginal
zone B-cell lymphoma, according to the clinical subtypes.
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| Fig 4.
Overall survival of the 124 patients with marginal zone
B-cell lymphoma, according to the clinical subtypes.
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Response to treatment varied in the different subtypes, and a CR was
reached in 69% of nodal subtype compared with <30% in the other
subtypes, but a partial response was the rule in these cases and truly
refractory patients were rare (Table 2). A high CR rate was not
associated with a longer TTP. Most of the patients with bone marrow
involvement at time of diagnosis had a persisting involvement at the
end of the treatment. However, TTP in these partial response patients
was not worse than the TTP of patients who reached a CR.
Transformation
Twenty patients presented a histological transformation during the
course of the disease. This diagnosis was made when a patient progressed with a high component of large cells or sheets of large cells in the new biopsy. This transformation was observed in first or
subsequent progression and occurred with a median time of 4.5 years
after the diagnosis (extreme: 1 year and 22 years). The clinical
picture of the disease at time of transformation was not different of
what has been described in the transformation of other indolent
lymphoma: presence of B symptoms (8 patients), poor performance status
(7 patients), bulky tumor (5 patients), extranodal locations other than
bone marrow (13 patients), and high LDH level (14 patients). Response
to treatment was poor, and survival after transformation was usually short.
Parameters associated with a good outcome
None of the studied initial parameters (Table
5) was associated with a poorer survival.
This may be related to the fact that overall survival is good in our
short series. None of the classical prognostic parameters, such as
those of the International Prognostic Index, was associated with a
shorter TTP. However, the absence of peripheral lymph nodes and the
presence of spleen involvement or blood involvement were associated
with a longer TTP (Table 5 and Figure 5).
No difference was observed between the three histological subtypes.
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Table 5.
Parameters associated with a longer time to progression
and a longer survival in the 124 patients with non-MALT MZL
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| Fig 5.
Time to progression survival according to the presence or
absence of blood involvement (X2 = 4.5,
P < .05).
Blood involvement was defined by either an excess of blood lymphocytes
(> 5 × 109/L) or presence of abnormal cells.
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Discussion |
In this review, we have collected all patients with lymphoma who did
not fit well into the new lymphoma classifications and reclassified
them. We were able to find 124 cases of marginal non-MALT lymphoma with
a satisfactory morphologic and clinical description. However, their
treatment was quite heterogeneous, and, if this study may add to the
knowledge of this newly described lymphoma, we are not able to describe
the best therapeutic options for these patients. We were able to
recognize without much difficulty the different morphologic aspects:
splenic lymphoma with or without villous lymphocytes, nodal lymphoma
with monocytoid B-cells, and cases with plasmacytic differentiation
being in the past classified as immunocytoma (Figure 1B). However, we
found histological aspects that did not fit very well in the proposed
classifications, particularly cases with a high component of large
cells at diagnosis, sometimes considered as a composite lymphoma at
diagnosis. Because of the same phenotype observed in small and large
cells, we prefer the name of large-cell variant to the name
"composite lymphoma" that may suggest two origins of the lymphoid
proliferation. This description does not mean that these patients must
be treated as having an indolent lymphoma: The treatment has to be
decided on the presence of clinical aggressiveness. Clearly, we need
more work on a larger group of patients to propose a definitive
classification for these lymphomas.
We described four clinical subtypes corresponding to the primary
clinical aspects, two of them, splenic and nodal subtypes, being the
subtypes proposed in the REAL and the WHO classifications. The splenic
lymphomas are characterized by a predominantly enlarged spleen with
frequent bone marrow and blood involvement. In some patients, abdominal
lymph nodes may be observed. Contrarily, the nodal subtype is
characterized by localized or disseminated lymph nodes with rare blood
involvement. Disseminated cases represent cases with a disease too
disseminated to identify the site of origin or the initial (or primary)
site of the disease. These cases represent probably a late stage of the
disease for either nodal or splenic subtypes. Contrarily, leukemic
cases may represent early diagnosis of a splenic subtype with a small
splenomegaly or no enlargement of the spleen at all. This last
hypothesis is comforted by the fact that these patients have a disease
that shares the same characteristics as those of splenic cases, and they have a very good outcome.
If the survival of these patients was truly good, defining these
lymphomas as indolent lymphomas, TTP is clearly different between the
splenic subtype and nodal or disseminated subtypes. Splenic MZL, with
or without villous lymphocytes, is obviously an indolent lymphoma with
difficulty to reach a CR whatever the treatment is, but with long TTP
and survival. Splenectomy was done in our patients without adverse
parameters, and it was associated with a very long TTP (Figure
6). Contrarily, nodal MZL may be a
localized disease, but the disease progressed very rapidly with the
therapy we have used. Even if TTP was short, survival is longer, and
this seems linked to the responses observed with salvage therapy. Disseminated MZL is a more aggressive disease, often with large-cell component and poor prognosis parameters, and it probably represents the
end stage of the other subtypes.
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| Fig 6.
Time to progression in the splenic subtype patients
according to the type of initial treatment. It is of note that the
initial treatment was decided according to the clinical presentation at
time of diagnosis and that CHOP chemotherapy was always realized in
patients with a more aggressive picture.
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The therapeutic strategy may not be defined after this
retrospective analysis, but we may give some recommendations for
future prospective studies or for the day-to-day care of these
patients. First, a correct diagnosis needs in many cases at least
immunophenotyping and often cytogenetic analysis, with nevertheless
some persisting borderline cases. A review by a panel of
hematopathologists seems necessary in prospective trials and to foresee
a cytogenetic examination is recommended. Second, splenic and leukemic
MZLs are clearly indolent lymphomas, and a conservative treatment is
probably the best choice, particularly for old patients.
Splenectomy may be done when the increase in spleen volume is too
important or when cytopenia occurs. Finally, nodal and
disseminated subtypes, particularly those with a component of
large cells or composite lymphoma, are more aggressive, and CHOP may be
considered as a first-line treatment.
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Acknowledgments |
We would like to thank the Programme National de Recherche Clinique
(PNRC Lyon 97-062), the Comitès Dèpartementaux de la Ligue
Nationale contre le Cancer du Rhùne, de l'Ardëche et de la
Saùne et Loire for funding this study.
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Footnotes |
Submitted September 27, 1999; accepted November 22, 1999.
Reprints: B. Coiffier, Service d'Hèmatologie, Centre
Hospitalier Lyon-Sud, 69495 Pierre-Bènite Cedex, France; e-mail: bertrand.coiffier{at}chu-lyon1.fr.
The publication costs of this
article were defrayed in part by
page charge payment. Therefore,
and solely to indicate this fact,
this article is hereby marked
"advertisement"
in accordance with 18 U.S.C.
section 1734.
| |
References |
1.
Harris NL, Jaffe ES, Stein H, et al.
A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group.
Blood.
1994;84:1361[Free Full Text].
2.
Isaacson PG, Spencer J.
Malignant lymphoma of mucosa-associated lymphoid tissue.
Histopathology.
1987;11:445[Medline]
[Order article via Infotrieve].
3.
Pileri SA, Milani M, Fraternali-Orcioni G, Sabattini E.
From the REAL classification to the upcoming WHO scheme: a step toward universal categorization of lymphoma entities?
Ann Oncol.
1998;9:607[Free Full Text].
4.
Jaffe ES, Harris NL, Diebold J, Muller-Hermelink HK.
World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: a progress report.
Am J Clin Pathol.
1999;110:s8.
5.
Isaacson PG, Matutes E, Burke M, Catovsky D.
The histopathology of splenic lymphoma with villous lymphocytes.
Blood.
1994;84:3828[Abstract/Free Full Text].
6.
Schmid C, Kirkham N, Diss T, Isaacson PG.
Splenic marginal zone cell lymphoma.
Am J Surg Pathol.
1992;16:455[Medline]
[Order article via Infotrieve].
7.
Catovsky D, Matutes E.
Splenic lymphoma with circulating villous lymphocytes/splenic marginal-zone lymphoma.
Sem Hematol.
1999;36:148[Medline]
[Order article via Infotrieve].
8.
Sheibani K, Sohn CC, Burke JS, Winberg CD, Wu AM, Rappaport H.
Monocytoid B-cell lymphoma: a novel B-cell neoplasm.
Am J Pathol.
1986;124:310[Abstract].
9.
Nathwani BN, Drachenberg MR, Hernandez AM, Levine AM, Sheibani K.
Nodal monocytoid B-cell lymphoma (nodal marginal-zone B-cell lymphoma).
Sem Hematol.
1999;36:128[Medline]
[Order article via Infotrieve].
10.
The Non-Hodgkin's Lymphoma Pathologic Classification Project.
National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: summary and description of a Working Formulation for Clinical Usage.
Cancer.
1982;49:2112[Medline]
[Order article via Infotrieve].
11.
Lennert K, Feller AC.
Histopathologie der Non-Hodgkin Lymphome (nach der acktulisierten Kiel-Klassifikation). Berlin, Germany: Springer Verlag; 1990.
12.
Berger F, Felman P, Sonet A, et al.
Nonfollicular small B-cell lymphomas: a heterogenous group of patients with distinct clinical features and outcome.
Blood.
1994;83:2829[Abstract/Free Full Text].
13.
Fisher RI, Dahlberg S, Nathwani BN, Banks PM, Miller TP, Grogan TM.
A clinical analysis of two indolent lymphoma entities: mantle cell lymphoma and marginal zone lymphoma (including the mucosa-associated lymphoid tissue and monocytoid B-cell subcategories): a Southwest Oncology Group study.
Blood.
1995;85:1075[Abstract/Free Full Text].
14.
Isaacson PG, Wotherspoon AC, Diss T, Pan LX.
Follicular colonization in B-cell lymphoma of mucosa-associated lymphoid tissue.
Am J Surg Pathol.
1991;15:819[Medline]
[Order article via Infotrieve].
15.
Dierlamm J, Pittaluga S, Wlodarska I, et al.
Marginal zone B-cell lymphomas of different sites share similar cytogenetic and morphologic features.
Blood.
1996;87:299[Abstract/Free Full Text].
16.
Dierlamm J, Michaux L, Wlodarska I, et al.
Trisomy 3 in marginal zone B-cell lymphoma: a study based on cytogenetic analysis and fluorescence in situ hybridization.
Br J Haematol.
1996;93:242[Medline]
[Order article via Infotrieve].
17.
Sole F, Woessner S, Florensa L, et al.
Frequent involvement of chromosomes 1, 3, 7 and 8 in splenic marginal zone B-cell lymphoma.
Br J Haematol.
1997;98:446[Medline]
[Order article via Infotrieve].
18.
Isaacson PG.
Gastrointestinal lymphoma.
Hum Pathol.
1994;25:1020[Medline]
[Order article via Infotrieve].
19.
Thieblemont C, Bastion Y, Berger F, et al.
Mucosa-associated lymphoid tissue gastrointestinal and nongastrointestinal lymphoma behavior: analysis of 108 patients.
J Clin Oncol.
1997;15:1624[Abstract].
20. Thieblemont C, Berger F, Dumontet C, et al. Mucosa-associated lymphoid
tissue (MALT) lymphoma is a disseminated disease in one third of the
patients: analysis of 159 patients. Blood. In press, 2000.
21.
Jaffe ES, Harris NL, Diebold J, Muller-Hermelink HK.
World Health Organization classification of lymphomas: a work in progress.
Ann Oncol.
1998;9:25.
22.
Callet-Bauchu E, Rimokh R, Tigaud I, et al.
Dic(4-17)(p11;p11): a new recurrent chromosomal abnormality in chronic B-lymphoid disorders.
Genes Chromosomes Cancer.
1996;17:185[Medline]
[Order article via Infotrieve].
23.
Coiffier B.
Fourteen years of high-dose CHOP (ACVB regimen): preliminary conclusions about the treatment of aggressive-lymphoma patients.
Ann Oncol.
1995;6:211[Free Full Text].
24.
Kaplan EL, Meier P.
Nonparametric estimation from incomplete observations.
J Am Stat Assoc.
1958;53:157.
25.
Peto R, Pike MC, Armitage PEA.
Design and analysis of randomized clinical trials requiring prolonged observations of each patient, II: analysis and examples.
Br J Cancer.
1977;35:1[Medline]
[Order article via Infotrieve].
26.
Cox J.
Regression models and life-tables.
J R Stat Soc.
1972;34:187.
27.
The International Non-Hodgkin's Lymphoma Prognostic Factors Project.
a predictive model for aggressive non-Hodgkin's lymphoma.
N Engl J Med.
1993;329:987[Abstract/Free Full Text].
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Abstract
Introduction