96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...

Abstracts
DO-053
Account of tumor infiltrating macrophages is a prognostic factor
for patients with mantle cell lymphoma
C . Schrader 1 , F . Sirin 1 , P . Meusers 2 , G . Brittinger 2 , J . Claasen 1 , W . Klapper 3
1 University Hospital of Kiel, 2 nd Department of Medicine, Kiel, 2 University
Essen, Department of Hämatology, 3 UKSH, Campus Kiel, Department of
Pathology
Aims. Mantle cell lymphoma (MCL) is a malignant lymphoma associated
with a relatively aggressive clinical course and a median overall survival
time of 3–4 years. Only limited data about tumor associated macrophages
and their influence on survival in MCL exists.
Methods. We analyzed the amount of CD68 macrophages in relation to
the clinical outcome in patients with MCL. Lymph node biopsies of 77
untreated patients (17 women and 60 men) enrolled in two multicenter
trials (1975–1985) with a median age of 66 years (range 41–86 years) were
included in this study. Biopsy specimens were investigated immunohistochemically
with monoclonal antibodies against CD68 (Ki-M1P).
10 High power fields (HPF) were evaluated by random.
Results. Patients with low account (less than 10/HPF) of CD 68 positive
macrophages had a median overall survival time of 38.2 months, compared
to 24.2 months for patients with high (more 10/HPF) CD 68 positive
macrophages. The Kaplan-Meier analysis showed a significant difference
in the overall survival time (p=0.0027).
Conclusions. Patients with mantle cell lymphoma and a low number of
CD 68 positive macrophages have a better prognosis and can predict
outcome.
DO-054
Transformation of gastritis to gastric marginal zone lymphoma is
associated with deregulated expression of microRNAs
C . Thorns1 , J . Kuba1 , A .C . Feller1 , V . Bernard 1 , A . Senft2 , S . Szymczak2 ,
H .-W . Bernd1 1 2 UKSH, Campus Lübeck, Pathology, University Lübeck, Institute for medical
bioinformatics and statistics
Aims. Gastric extranodal marginal zone lymphoma (MALT lymphoma)
generally evolve from a chronic Helicobacter pylori-positive gastritis.
The mechanisms that promote the malignant transformation from gastritis
to lymphoma are not well understood. This study aims to identify
microRNAs that might be involved in the process of neoplastic transformation.
Methods. Gastric biopsies were scored as 0 (normal), 1 (gastritis), 2 (follicular
gastritis), 3 (suspicious, probably reactive), 4 (suspicious, probably
lymphoma) and 5 (MALT lymphoma) (Wotherspoon scores). Groups 3,
4, and 5 were further evaluated for monoclonality by immunohistochemistry
for immunoglobulin light chains and/or by polymerase-chainreaction
for the immunoglobulin heavy chain locus (IgH). MicroRNAsignatures
of 68 cases were generated by RT-PCR for 376 miRNAs.
Results. MicroRNA signatures revealed a total of 41 miRNAs that were
significantly upregulated (n=33) or down regulated (n=8) in succession
from normal mucosa to gastritis and to MALT-lymphoma. Some of these
reflect the normal expression in lymhocytes (e.g. miR-566 and -212),
while others are known to be the effect of Helicobacter pylori infection
(e.g. miR-155 and let7f). A group of five miRNAs (miR-150, -550, -124a,
-518b and -539) were differentially expressed in gastritis (Wotherspoon
scores 1, 2 and polyclonal 3 and 4) and lymphomas (monoclonal scores 3,
4, and 5). These are likely to be involved in the malignant transformation
of gastritis into MALT lymphoma.
Conclusions. The development of gastric MALT-lymphoma out of chronic
gastritis is paralleled by the deregulation of distinct microRNAs
which might thus be centrally involved in the process of malignant
transformation.
28 | Der Pathologe · Supplement 1 · 2012
AG Hämatopathologie II
DO-055
Bcl6 expression is not limited to germinal center B-cells and is
associated with progression of extranodal marginal zone B-cell
lymphomas of the gastrointestinal tract
U . Boruschek1 , L . Floßbach1 , M . Buck1 , S . Brüderlein1 , P . Möller1 , T .F .E . Barth1 1Ulm University, Pathology, Ulm
Aims. We have previously shown that progression in gastrointestinal
B-cell lymphomas is associated with changes in the BCL6 locus and
with an increased expression of Bcl6 [Flossbach et al. Int J Cancer 2011;
129(1):70–7]. Bcl6 is a well known germinal center marker; the extranodal
marginal zone B-cell lymphomas (MALT lymphomas) are supposed to
stem from cells of the extrafollicular space, therefore the expression of
Bcl6 in these lymphomas during progression seems conflicting. We have
analyzed the detailed expression of Bcl6 in lymph nodes with toxoplasmosis
since one of the cells discussed to be the potential progenitor of
MALT lymphomas is the monocytoid B-cell.
Methods. We studied lymph node paraffin sections of four patients with
toxoplasmosis by double immunofluorescence staining using a broad
panel of antibodies. For this purpose we first established a new technique
based on sequential heating of the samples that now even allows the
application of antibodies from the same species or the simultaneous use
of monoclonal and polyclonal antibodies. Further we performed stimulation
experiments with lymphoblastoid B-cells.
Results. We found a strong expression of Bcl6 in the germinal center. However,
we also detected some scattered Bcl6 positive cells in the extrafollicular
space. These extrafollicular Bcl6-positive cells were characterized
as: CD19+,CD75+, AID+, IgA+, IgG+/−, CD30−, CD10−, CD38−, Bcl2−,
ZAP70−, cRel−, IgM−, IgD−, CD11c−. Monocytoid B-cells expressed
Bcl6 in a subfraction of less than 1%. The profile of the Bcl6+ extrafollicular
B-cells corresponds to an activated post germinal center B-cell differing
from monocytoid B-cells. Expression of Bcl6 was partially inducible
in lymphoblastoid EBV transformed B-cells by TNFα, TPA, and LPS.
Conclusions. We conclude that Bcl6 expression is not limited to germinal
B-cells but is also found in extrafollicular B-cells. We suggest that the
blastic variant of MALT lymphoma may have preserved the potential of
up-regulating Bcl6 as an antiapoptotic mechanism.
DO-056
Characterization of gastrointestinal marginal zone B-cell lymphoma
and large cell variants using high-resolution SNP-arrays
L . Floßbach1 , K . Holzmann2 , T . Mattfeldt 1 , P . Möller1 , T .F .E . Barth1 1 2 Ulm University, Pathology, Ulm, Ulm University, IZKF, Ulm
Aims. Gastrointestinal marginal zone B-cell lymphomas (MALT Lymphomas)
are a model for tumor progression since we and others have
shown that the frequently coexisting more aggressive large cell component
is clonally related to the small cell lymphoma. We used SNP analysis
to further characterize these lymphomas.
Methods. We extracted genomic DNA from frozen tissue samples of 28
gastrointestinal marginal zone B-cell lymphomas (n=7) and large cell
variants (n=21). We performed SNP analysis using the Affymetrix HGW
SNP array 6.0 platform. Results were correlated with FISH and IHC analyses.
Results. While small cell lymphomas have on the average 8 aberrations
longer than 0.2MB each case, large cell variants have more than 14. Both
small and large cell lymphomas have losses in regions 1p13 and 6q15 as
well as gains on 1p36 and 17q21. Gains on 9q12i-j (2/7) are restricted to
small cell lymphomas. Losses on 6q24 (5/21) and gains on 11q23 (8/21)
are restricted to the large cell lymphomas. Most frequent losses or deletions
concern region 6q14.1a-c containing HTR1B, IRAK1BP1, PHIP,
HMGN3, LCA5 and SH3BGRL2 (5/21 large cell and 1/7 small cell lym-