Abstract
Background: Hodgkin Lymphoma (HL) constitutes 10% of lymphomas and 1% of cancers in industrialized nations, classified into classical Hodgkin Lymphoma (cHL) and nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHL). The four cHL subtypes include nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted. Etiologically, HL stems from B-cell clonal transformation, influenced by genetic predisposition and viruses like Epstein-Barr virus (EBV) and Human immunodeficiency virus (HIV). HL cells exhibit programmed death ligand 1 (PD-L1) overexpression, enabling immune evasion through interaction with PD-1 on T cells. The PD-1-PD-L1 axis is a promising therapeutic target, with ongoing scrutiny of PD-L1 identification by immunohistochemistry (IHC) in HL as a potential marker for immunotherapy efficacy.
Aim: To detect the frequency, and association between EBV & PDL-1 expression in Hodgkin lymphoma cases.To investigate the association between the expression of PD-L1 & EBV in Hodgkin lymphoma and some clinic-pathological parameters like age of patients & subtype.
Material and Methods: This is both a retrospective and prospective case series study which was conducted on 40 cases of Hodgkin Lymphoma, that were collected from private laboratories in the North of Iraq extending from November 2022 through September 2023. Reviewing of diagnosis & classification was done according to WHO of HL. PD-L1 & EBV status were evaluated immunohistochemically using intensity and percentage guided scoring for PD-L1 & cytoplasmic staining for EBV.
Results: In this study of 40 Hodgkin Lymphoma cases, the M: F was 3:2 & and nodular sclerosis subtype form the majority of cases (67.5%). PD-L1 expression occurred in (67.5%) of cases and (35%) in the tumor micro-environment. No significant associations were found with age, gender and subtype. EBV LMP-1 expression was found in (30%), with more frequency in males (83%), and associated with mixed cellularity HL subtype. PD-L1 intensity showed significant association with its cutoff in HRS cells and tumor microenvironment but not with EBV status, gender and HL subtype. PD-L1 and EBV LMP-1 expressions did not show a significant association.
Conclusion: In Hodgkin Lymphoma (HL), immunohistochemical expression of programmed death ligand 1 (PD-L1) is found in 67.5% of HL cases and 35% of the tumor micro-environment. However, there is no significant association between PD-L1 expression and the presence of EBV latent membrane protein-1 (LMP-1). Only 29.6% of patients with positive PD-L1 expression also show positive EBV LMP-1. Additionally, no significant associations were identified between PD-L1 expression and HL subtype, age, and gender. The expression of PD-L1 in the tumor micro-environment does not show a statistically significant difference when compared with HL subtypes. On the other hand, EBV LMP-1 immunohistochemical expression is significantly associated with male gender (83.3%) and certain histological subtypes but reveals no statistically significant difference concerning the age of the patients.