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Home > Prevalence of Double Myc/Bcl2 Expression and the Cell of Origin in Diffuse Large B-Cell Lymphomas Diagnosed at a Tertiary Level Referral Laboratory

Prevalence of Double Myc/Bcl2 Expression and the Cell of Origin in Diffuse Large B-Cell Lymphomas Diagnosed at a Tertiary Level Referral Laboratory

Thesis Info

Author

Wawire, Jonathan

Department

Pathology (East Africa)

Program

MMed

Institute

Aga Khan University

Institute Type

Private

City

Karachi

Province

Sindh

Country

Pakistan

Thesis Completing Year

2017

Thesis Completion Status

Completed

Subject

Medicine

Language

English

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676728061016

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Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most commonly diagnosed non-Hodgkin’s lymphoma in adults worldwide. In Kenya DLBCL accounts for 64% of all non-Hodgkin’s lymphomas diagnosed in adults. It is a heterogeneous disease and patients show varying outcomes despite standard treatment. This variability is attributed to the differences in the biology and molecular pathogenesis of DLBCL. The five most important prognostic factors for DLBCL include scores for the revised international prognostic index (R-IPI), the cell of origin (COO), presence of myelocytomatosis (MYC) and B-cell lymphoma 2 (BCL2) gene rearrangements by fluorescent in situ hybridisation (FISH) or standard cytogenetics, the absolute lymphocyte and monocyte count, and imaging with positron emission tomography (PET scan). Current data shows that the use of immunohistochemistry in identifying cases of DLBCL with MYC and BCL2 protein over-expression (double-expressing lymphomas) yields important prognostic information since these patients form a higher proportion of cases compared to those with concurrent MYC and BCL2 translocations (double-hit lymphomas) using FISH/cytogenetics . The double expressing DLBCL have a poorer prognosis compared to cases of DLBCL lacking MYC/BCL2 double-expression. With advances in targeted therapy for DLBCL, it is important to also identify patients who may benefit from new regimens by determining their cell of origin. Gene expression profiling (GEP), the technique for determining the COO is not available to the routine diagnostic laboratory. Consequently, robust immunohistochemistry surrogates have been developed in place of GEP for this purpose. Hans’ algorithm which uses three antibodies in sequence (CD10, BCL6 and MUM1) is the most widely applied for determining COO. The World Health Organization (WHO) guidelines currently recommend definition of the cell of origin and testing for double MYC/BCL2 expression for every patient diagnosed with diffuse large B cell lymphoma. Furthermore, in order to establish a diagnosis of DLBCL, NOS with certainty, other high-grade B-cell lymphomas, such as Burkitt lymphoma and plasmablastic lymphoma, need to be excluded. This can be achieved by a comprehensive antibody panel that includes MYC and BCL2. These antibodies need to be optimised and standardised for the settings in which a particular laboratory operates. Objectives: To determine the prevalence of MYC/BCL2 double-expression among diffuse large B cell lymphomas diagnosed at The Aga Khan University Hospital, Nairobi (AKUH, N) Laboratory. To define the cell of origin of DLBCL diagnosed at AKUH, N laboratory. Methods: Formalin fixed Paraffin embedded (FFPE) blocks of DLBCL cases diagnosed between January 1st 2012 and December 31st 2015
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