An observational study in Non Hodgkin Lymphoma, Follicular Lymphoma and Marginal Zone Lymphoma, sponsored by Hospices Civils de Lyon. Active, not recruiting at 1 site in France. Open to participants aged 25 Years to 100 Years. Per ClinicalTrials.gov, last updated 2024-05-23.
Sponsored by Hospices Civils de Lyon · Observational
Non-Hodgkin lymphomas (NHLs) constitute a heterogeneous group of malignant neoplasms, with diverse clinical behaviors and distinct pathologic and molecular characteristics. Among these lymphomas, follicular lymphomas (FLs), marginal zone lymphomas (MZLs) and diffuse large B-cell lymphomas (DLBCLs) emerge as the most prevalent entities. While FL and MZL are representative of indolent B-cell lymphomas, characterized by a slow progression of the disease and favorable clinical outcomes, DLBCL stands out as an aggressive lymphoma, often occuring from the transformation of a pre-existing indolent lymphoma.
Chromosome translocations are a hallmark of some NHL subtypes, offering insights into their molecular pathogenesis. For instance, the conventional FL is genetically characterized by the t(14;18) chromosomal translocation, found in 85-90% of cases, resulting in sustained elevation of the antiapoptotic protein B-cell lymphoma 2 (BCL2). However, certain FL cases lack BCL2 translocations and exhibit distinct clinical, morphological and phenotypical features with genetic heterogeneity.
A subset of BCL2-negative FLs displays rearrangements within chromosomal region 3q27, inducing abnormal modulation of B-cell lymphoma 6 (BCL6) expression. The BCL6 gene plays a critical role in germinal center development and B-cell differentiation. Previous investigations indicate that BCL6 rearrangements (BCL6-R) manifest distinct pathological and genetic features, diverging from classical FL presentations.
FLs carrying BCL6-R commonly share a specific CD10- Bcl-2- Bcl-6+ phenotype, often accompanied by a monocytoid component and increased frequency of diffuse architectural patterns. Patients with BCL6-R tend to exhibit advanced clinical stages and complex genetic profiles.
MZLs present differential diagnostic challenges due to shared monocytoid components, phenotypes traits, and common genetic features. The similarities observed between BCL6-R FL and MZL suggest a convergence in both morphological and genetic aspects, leading to intricate differentiation. Traditionally, these indolent NHLs with BCL6-R were categorized as FL and incorporated into the FL category in the WHO classification. However, few studies highlight the occurrence of BCL6-R in MZLs. This observation gives rise to the hypothesis that indolent NHLs exhibiting BCL6-R might correspond to a continuum comprising both FL and MZL.
Additionally, BCL6-R has been frequently documented in DLBCL cases with residual MZL component. These DLBCL cases might display a mutational profile reminiscent of MZL. This suggests a plausible origin of BCL6-R DLBCL from indolent BCL6-R MZLs or BCL6-R FLs cases.
5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.
This study's planned enrollment of 135 is close to the median of 136 across 625 observational studies indexed under Lymphoma.
Browse Lymphoma studies →Hospices Civils de Lyon is the lead sponsor of 1,826 studies on the registry; 439 are open to participants now.
Counted across the registry records on this site, refreshed daily.
All patients diagnosed with non-Hodgkin lymphoma from the routine diagnostic archives of the pathology department of CHU Lyon Sud between January 2016 and August 2023 and with BCL6-R detected by FISH analysis will be included in the study. A cohort of 135 cases will be assembled and subjected to the analysis.
This dataset will be reviewed by two haematopathologists to ensure the inclusion of the most relevant cases. Selection will favor cases with substantial histological material and available clinical, immunophenotypic and cytogenetic data. Comparative assessments will be conducted between distinct subtypes of NHL exhibiting BCL6-R, including FLs, MZLs, and DLBCLs.
Exclusion Criteria:
Diagnoses of follicular lymphomas based on the last World Health Organization (WHO) classification of haematolymphoid tumours at the time of occurrence of the disease. Fluorescence in situ hybridization (FISH) utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols.
Other: Histopathological analysis · Genetic: Molecular analysis
Diagnoses of marginal zone lymphomas based on the last WHO classification of haematolymphoid tumours at the time of occurrence of the disease. FISH utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols.
Other: Histopathological analysis · Genetic: Molecular analysis
Diagnoses of diffuse large B-cells lymphomas based on the last WHO classification of haematolymphoid tumours at the time of occurrence of the disease. FISH utilizes Vysis' Dual-Color Break-Apart Rearrangement Probes to detect BCL6 gene alterations. FISH patterns have been interpreted following established protocols.
Other: Histopathological analysis · Genetic: Molecular analysis
Morphological analysis will include the description of architectural patterns and cytological features on formalin-fixed and paraffin-embedded (FFPE) tissue samples retrieved from the routine diagnostic archives of the Pathology Department of the University Hospital Lyon Sud. A panel of immunohistochemical staining will be analyzed including CD20, CD3, CD10, Bcl-6, Bcl-2, CD5, CD23, CD38, MUM1, Ig kappa, Ig lambda, MEF2B, LMO2, MNDA, IRTA1, P53, CMYC and Ki67 . /MIB1. Diffuse large B-cells lymphomas will be classified into two distinct subgroups: centro-germinative (GC) and non-centro-germinative (nGC), using the Hans algorithm.
Next-generation sequencing (NGS) analysis will be performed on FFPE tissue samples retrieved from the routine diagnostic archives of the Pathology Department of the University Hospital Lyon Sud. A panel of 73 genes dedicated to lymphoma diagnosis determined by a consensus of French Lysa experts will be used. The identification of genetic variants will be followed by the attribution of pathogenicity class in accordance with the guidelines for validation of NGS-based oncology panels. RNA extraction will classify DLBCLs into two distinct subgroups: germinal-centre B-cell-like (GCB-DLBCL) and activated B-cell-like (ABC-DLBCL).
Comparison of LF and MZL with BCL6-R.
An examination of morphological attributes, including tissue architecture and cellular patterns will be performed on LF and MZL with BCL6-R. An extended immunohistochemical staining panel employing incorporated novel centro-germinative markers (LMO2 and MEF2B) and recently identified MZL-specific markers (IRTA1 and MNDA) is planned.
Time frame: The primary outcome will be analyzed retrospectively, or through study completion, an average of 1 year
Comparison of LF and MZL with BCL6-R.
Fluorescence in situ hybridization (FISH) will be employed for cytogenetic evaluation to detect BCL2 and BCL6 gene rearrangements. In parallel, targeted next-generation sequencing (NGS) analysis will enable genetic variant detection.
Time frame: The primary outcome will be analyzed retrospectively, or through study completion, an average of 1 year
Plan to share: No
No publications or documents are linked to this record.
This study is active, not recruiting, as verified in May 2024. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Hospices Civils de Lyon