10 research outputs found
Gray zones around diffuse large B cell lymphoma. Conclusions based on the workshop of the XIV meeting of the European Association for Hematopathology and the Society of Hematopathology in Bordeaux, France
The term âgray-zoneâ lymphoma has been used to denote a group of lymphomas with overlapping histological, biological, and clinical features between various types of lymphomas. It has been used in the context of Hodgkin lymphomas (HL) and non-Hodgkin lymphomas (NHL), including classical HL (CHL), and primary mediastinal large B cell lymphoma, cases with overlapping features between nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B cell lymphoma, CHL, and EpsteinâBarr-virus-positive lymphoproliferative disorders, and peripheral T cell lymphomas simulating CHL. A second group of gray-zone lymphomas includes B cell NHL with intermediate features between diffuse large B cell lymphoma and classical Burkitt lymphoma. In order to review controversial issues in gray-zone lymphomas, a joint Workshop of the European Association for Hematopathology and the Society for Hematopathology was held in Bordeaux, France, in September 2008. The panel members reviewed and discussed 145 submitted cases and reached consensus diagnoses. This Workshop summary is focused on the most controversial aspects of gray-zone lymphomas and describes the panelâs proposals regarding diagnostic criteria, terminology, and new prognostic and diagnostic parameters
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Paraffin-Based 6-Gene Model Predicts Outcome of Diffuse Large B-Cell Lymphoma Patients Treated with R-CHOP
Abstract
Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by highly variable clinical outcomes. It is therefore of paramount importance to be able to predict the outcome of patients at the time of diagnosis. Previously, we constructed a 6 gene model for outcome prediction of DLBCL patients treated with anthracycline-based chemotherapies (Lossos et al NEJM 2004, 350:1829). However, the standard therapy has evolved to rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). Subset analyses of clinical trials have suggested that some of the prognostic factors lose their predictive power in R-CHOP treated patients. Consequently, the molecular gold standard for survival prediction in R-CHOP treated patients has not been established. Herein, we evaluated the predictive power of the 6-gene model in R-CHOP treated DLBCL patients. We have employed new methodology that allows quantitation of gene expression from paraffin embedded, fixed tissues.
Methods: RNA was extracted from 100 paraffin-embedded specimens (Chen et al Diagn Mol Pathol 2007, 16:61), from patients with DLBCL treated with R-CHOP in British Columbia (73) and at the University of Miami (27). Expression of the 6 genes comprising the model was measured in these samples and the mortality-prediction score was calculated for each patient, as reported previously.
Results: The study group consisted of 100 patients with a median age of 58 y (range, 16â92y) that were followed for a median of 2.1 years (range, 0.1â5.6). Distribution according to IPI: 0â1 factor, 42; 2 factors, 24; 3 factors, 19; and â„4 factors, 14. RNA of sufficient quality and quantity was successfully extracted from all the 100 paraffin embedded specimens tested, some of which had been stored for up to 6 years. The mortality-prediction score derived from the model divided patients into low-risk (50%) and high-risk (50%) subgroups with significantly different overall survival (OS) (p=0.02) and progression free survival (PFS) (p=0.02). Notably the OS was similar between the groups during the 1st year, due to the inclusion of patients with advanced age and poor performance status, but it was markedly different beyond the first 2 years, with the 3 year OS of 80% and 50% in the low risk and high risk groups, respectively. The predictive power of the 6-gene model was independent of the IPI prognostic factors for prediction of OS (P=0.06) and PFS (p=0.01) in these patients.
Conclusions: The prognostic value of the 6-gene model remains significant in the era of R-CHOP treatment. Further, using the new RNA extraction methodology, we demonstrate that the model can be applied to routinely available formalin-fixed paraffin blocks from initial diagnostic biopsies, even after long term storage. Following validation in an independent cohort of patients, the six gene model may be practically applied in routine clinical practice
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Expression of HGAL in primary cutaneous large B-cell lymphomas: evidence for germinal center derivation of primary cutaneous follicular lymphoma
The classification of primary cutaneous large B-cell lymphoma (PCLBCL) is based on standard morphology, immunohistochemistry, and clinical presentation. There are two major subtypes in the current WHO-EORTC classification: follicle center lymphoma and diffuse large B-cell lymphoma, leg-type (DLBCL-LT). The goals of this study were to examine a series of DLBCLs to determine (1) whether the immunohistochemical paradigm of germinal center B-cell and non-germinal center B-cell types of systemic DLBCL could be applied to PCLBCL; (2) whether application of the newly described germinal center B-cell marker, human germinal center-associated lymphoma (HGAL) also discriminates between these types as a further support for germinal center B-cell origin for primary cutaneous center lymphoma; and (3) whether any of these biologic markers were of prognostic significance. To this end, 32 cases of diffuse PCLBCL (22 primary cutaneous follicular center lymphomas and 10 DLBCL-LT) were classified based on the WHO-EORTC criteria and studied for expression of CD20, BCL2, BCL6, CD10, MUM-1, and HGAL by immunohistochemistry. Results were correlated with clinical features. HGAL and BCL6 expression and germinal center B-cell phenotype were associated with primary cutaneous follicular center lymphoma. The combination of HGAL and BCL6 positivity had the highest sensitivity (88%) and specificity (100%) for predicting subtype compared to either marker alone. Both HGAL and BCL6 were associated with the germinal center B-cell phenotype. The correlation of HGAL expression with the germinal center B-cell phenotype demonstrates the role of this marker in the classification of cutaneous large B-cell lymphomas. BCL6 expression was the only immunohistochemical marker associated with overall survival. Characterizing PCLBCLs with markers of B-cell maturation stage is a useful framework for studying, classifying, and clinically stratifying these lymphomas