Immunohistochemical Characterisation of Cell of Origin in Diffuse Large B-cell Lymphoma and its Association with the Double Expressor Phenotype: A Retrospective Study

Abstract

Introduction: Diffuse Large B-cell Lymphoma (DLBCL) is the most common type of Non-Hodgkin Lymphoma (NHL) and is categorised into the Germinal Centre B-cell (GCB) and Activated B-cell (ABC/Non GCB) subtypes as per the Cell Of Origin (COO) model with the help of gene expression profiling/immunohistochemistry. The non GCB subtype has been found to associate with the Double Expressor (DE) phenotype (i.e., co-expression of BCL-2 and c-myc by IHC and this association was substantiated and proven to be statistically significant in the present study. Aim: To categorise all DLBCL cases into GCB and Non GCB and further into DE and Non-DE by using Hans and Choi IHC alogrithm. Materials and Methods: A retrospective study of 50 patients was carried out with the help of archival material filed in the Department of Anatomic Pathology at Dharamshila Narayana Superspeciality Hospital, New Delhi, India from 1st January 2019 to 30th June 2020. The study was approved by Instituitional Ethics Committee (IEC). The study cohort was divided into two groups- group A with nodal presentation and group B with extranodal presentation. By using the Hans and Choi IHC algorithms, the cases were categorised into the GCB and non GCB subtypes in both the groups. Chi-square test and Yates correction were used for statistical analysis. Results: The median age at presentation was 49 years (20-81 years) with a male to female ratio of 2.3:1 (35 males and 15 females). Group A with nodal disease included 28 patients and group B with extranodal disease included 22 patients. The DE phenotype was determined in each case by the co-expression of c-myc (>40%) and BCL-2 (>50%) by IHC. By using the statistical chi-square test analysis and Yates correction, the association of DE was found to be statistically significant with non GCB type lymphomas and non DE with GCB lymphomas with p-value being 0.0005 and 0.00168, respectively. Conclusion: Due to the heterogeneity inherent in DLBCL, prediction of the DE phenotype and the COO by IHC is a sensitive tool and helps in the prognostication and therapeutic triage of patients. Hence, in all the cases diagnosed as DLBCL, a detailed morphological and IHC work up is mandatory to determine prognosis and possibly tailor therapy according to COO and DE phenotype.

Keywords

• cell of origin model
• hans and choi algorithm
• immunohistochemistry