96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...
96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...
96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...
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phomas). Most prominent gains or amplifications (6/21 large cell lymphomas)<br />
concern region 2p16.1a-15d containing PAPOLG, REL, PUS10<br />
and PEX13. Amplification of REL was confirmed by FISH in these cases.<br />
In all these lymphomas, immunohistochemical staining for c-Rel was<br />
positive in at least 30% of the tumor cells. Regions with putative acquired<br />
uniparental disomies (aUPD) are more present in the large cell lymphomas:<br />
on the average 40 regions vs. 9 regions in the small cell lymphomas.<br />
Comparing the SNP profiles of two areas of the same tumor both with<br />
a t(11;18) Api2/Malt1 but with slightly different morphology, the analysis<br />
revealed additional gains in the more blastic part. Investigating two<br />
lymphoma samples from the same patient with an interval of two years,<br />
FISH analysis showed a signal pattern pointing to a large deletion in the<br />
IGH locus exclusively in the later sample. SNP analysis confirmed the<br />
FISH result and revealed about ten additional aberrations illustrating increasing<br />
genomic complexity during lymphoma progression.<br />
Conclusions. Small and large cell variants of gastrointestinal marginal<br />
zone B-cell lymphomas have distinct patterns of genomic aberrations<br />
but share some overlapping features. REL is frequently amplified in the<br />
large cell variants. In general, during lymphoma progression, the SNP<br />
data correlate with a more complex pattern of aberrations.<br />
DO-057<br />
Comparative analysis of gene expression profiles defines large<br />
cell variants of gastric marginal zone B-cell lymphoma as a distinct<br />
subgroup<br />
L . Floßbach1 , J . Kraus2 , K . Holzmann3 , P . Möller1 , H .A . Kestler2 , T .F .E . Barth1 1 2 Ulm University, Pathology, Ulm, Ulm University, Neural Information Processing,<br />
Ulm, 3Ulm University, IZKF, Ulm<br />
Aims. Gastrointestinal marginal zone B-cell lymphomas (MALT Lymphomas)<br />
often collocalize with a more aggressive, large cell component.<br />
The WHO classifies these lymphomas as “extranodal DLBCL with or<br />
without residing MALT component”. We have shown that the small and<br />
the large cell components of these composite lymphomas (ComL) are<br />
mostly clonal and, in addition to that, that the gene expression profiles<br />
of small cell MALT lymphomas and lymphoma components are similar<br />
to those of the large cell components or lymphomas. This suggests<br />
that most of the gastrointestinal DLBCL are indeed blastic variants of<br />
marginal zone B-cell lymphomas (MZBL) [Barth et al., J Pathol 2007;<br />
211(3):305; Flossbach et al. Int J Cancer 2011 129(1):70]. To further distinguish<br />
these large cell variants of MZBL from nodal and extranodal<br />
DLBCL we performed a comparative analysis of gene expression profiles<br />
from B-cell lymphomas.<br />
Methods. We extracted RNA from frozen tissue samples of 28 gastrointestinal<br />
marginal zone B-cell lymphomas (n=7), large cell components<br />
of ComL (n=8) and large cell variants (n=13). Gene expression profiling<br />
was performed using the Affymetrix U 133 plus 2.0 array. Additional datasets<br />
created with the same chip from DLBCL (n=119), PMBL (n=20),<br />
BL (n=33), FL (n=38), MCL (n=7), pulmonary MALT lymphomas (n=35)<br />
and normal B-cells (n=20) were obtained from the Gene Expression<br />
Omnibus (GEO) database. After normalization and based on a subset of<br />
NF-κB target genes [Compagno et al., Nature, 459, 717, 2009], we performed<br />
hierarchical clustering analysis. Additionally, we performed cluster<br />
robustness analysis using the k-means algorithm.<br />
Results. Cluster number estimation was robust for k=8. These eight<br />
clusters consisted mostly of: 1. naïve B-cells and memory B-cells, 2. centroblasts<br />
and centrocytes, 3. Burkitt’s lymphoma, 4. pulmonary MALT<br />
lymphoma, 5. follicular lymphoma, mantle cell lymphoma, and gastrointestinal<br />
MALT lymphoma, 6. PMBL and DLBCL, 7. DLBCL, 8. blastic<br />
MZBL and DLBCL. The dendrogramm, generated by the hierarchical<br />
average linkage clustering process, was consistent with this classification.<br />
In comparison to all DLBCLs and PMBLs, the blastic MZBLs had<br />
relatively un<strong>der</strong>expressed PTPN3 and relatively overexpressed BANK,<br />
CD44, CD63, and FAS.<br />
Conclusions. These data confirm our view of blastic marginal zone B-cell<br />
lymphomas as a distinct group of extranodal diffuse large B-cell lymphomas.<br />
DO-058<br />
Prognostic phenotypic and genotypic in situ biomarkers in diffuse<br />
large B-cell lymphomas: preliminary translational report of the<br />
prospective SAKK 38/07 trial<br />
A . Tzankov1 , N . Leu1 , S . Muenst1 , D . Klingbiel2 , C . Mamot3 , S . Dirnhofer1 1 2 University Hospital Basel, Pathology, Basel, Switzerland, SAKK Coordinating<br />
Center, Swiss Group for Clinical Cancer Research, Bern, Switzerland,<br />
3Cantonal Hospital Aarau, Aarau, Switzerland<br />
Aims. Diffuse large-B cell lymphoma (DLBCL) exhibits variable outcomes<br />
and risk assessment is based on the international prognostic index<br />
(IPI), which takes into account primarily patient-related parameters. The<br />
prognostic role of tumor-related parameters is a matter of controversy.<br />
Methods. We prospectively analyzed the prognostic value of phenotypic<br />
and genotypic profiles suggested to play a role in DLBCL on a clinical trial<br />
collective of 124 DLBCL patients homogenously treated with six cycles<br />
of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone,<br />
followed by 2 cycles rituximab (R-CHOP). Evaluation of the role of positron<br />
emission tomography was a main objective, and was performed<br />
before, after 2 cycles of therapy and at the end of treatment. Immunohistochemical<br />
(BCL2, BCL6, CD5, CD10, CD20, CD95, CD168, Cyclin<br />
E, FOXP1, GCET, Ki-67, MUM1p, pSTAT3) and in situ hybridization<br />
analyses [BCL2 break apart probe (BAP), C-MYC BAP and C-MYC/<br />
IgH double-fusion probe (DFP) and Epstein-Barr virus probe (EBER)]<br />
were performed and correlated with clinicopathological parameters and<br />
outcome.<br />
Results. The median patients’ age was 59 years; 68 were males, 56 females.<br />
BCL2 gene breaks were observed in 11% of cases, and those cases also expressed<br />
BCL2 in a mean of 95% of tumor cells, compared to 42% in nonrearranged<br />
instances; 85% of the rearranged cases were of the germinal<br />
center (GC) phenotype according to the Tally algorithm. 3% of cases (all<br />
of the non-GC phenotype) showed BCL2 amplifications. C-MYC breaks<br />
were observed in 10% of cases; 66% were of the GC phenotype. Of the C-<br />
MYC rearranged cases only a third displayed C-MYC/IgH fusions corresponding<br />
to t(8;14), the others being assumed to have alternative C-MYC<br />
rearrangement partners. Cases with rearranged C-MYC showed as high<br />
Ki-67 labeling as non-rearranged. Cases with both BCL2 and C-MYC<br />
rearrangements were not observed. A complete response (CR) defined<br />
by Cheson’s criteria was achieved in 90 out of 117 patients, for 7 there<br />
were no data. Factors that were linked to failure to achieve CR were CD5<br />
positivity (11% compared to 2%, p=0.051), EBER positivity (4% of cases<br />
compared to 0% of those with CR, p=0.072) and presence of either BCL2<br />
or C-MYC gene rearrangements (46% compared to 18%, p=0.132), but not<br />
IPI or Tally phenotype.<br />
Conclusions. Phenotypic and genotypic studies with carefully selected<br />
biomarkers like CD5, EBER and BCL2- as well C-MYC BAP might be of<br />
prognostic value in DLBCL patients treated by R-CHOP.<br />
DO-059<br />
Phenotype of primary testicular diffuse large B-cell lymphomas<br />
T . Menter1 , M . Ernst1 , S . Dirnhofer1 , A . Braghorn2 , P . Went1 , A . Tzankov1 1University of Basel, Institute of Pathology, Basel, Switzerland,<br />
2Medica Zürich, Switzerland<br />
Aims. Primary testicular diffuse large B-cell lymphomas (tDLBCL) are<br />
rare neoplasms with few comprehensive studies conducted so far. We<br />
therefore aimed to systematically analyze the morphology and phenotype<br />
of tDLBCL.<br />
Der Pathologe · Supplement 1 · 2012 |<br />
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