Assessment of Expressor Lymphoma Prevalence in High-Grade Large B-cell Lymphomas: An Observational Analysis From a Tertiary Care Centre

Abstract

Double or Triple Hit Lymphomas (DHL/THL) represent a subset of aggressive B-cell lymphomas with markedly poorer outcomes and survival rates compared to Diffuse Large B-cell Lymphomas, NOS (DLBCL, NOS). Identifying the Hit status in High-grade large B-cell lymphoma (HGBL)/ Diffuse Large B-cell Lymphomas (used synonymously henceforth) can aid in identifying cases with aggressive clinical course that may benefit from more intensive chemotherapy. Utilizing immunohistochemistry (IHC) to detect Expressor Lymphomas (EL) provides a simpler and cost-effective means to screen DLBCL cases for further molecular studies aimed at identifying potential Hit status. Our investigation aimed to assess the occurrence of Expressor Lymphoma cases in the Indian population and compare clinical (age, gender, site of tumor and B-symptoms) and pathological parameters {Ki67 proliferation index and Germinal Centre/Non-Germinal Centre (GC/Non-GC) phenotype} between Expressor and Non-Expressor Lymphomas (NEL). The present study included 131 patients diagnosed with HGBL. Men comprised 62.6% of patients, with 58% aged 60 years or younger. Clinical data on the occurrence of B-symptoms was accessible for 99 patients, with only 35 of them displaying such symptoms. Serum LDH levels were measured in 34 of the 131 total cases, and 30 of these showed elevated levels. Nodal disease was present in 26% of cases, while the remaining had extranodal involvement. The GC phenotype was observed in 58.8% of cases. Out of 131 cases, 22.2% were EL, while 77.8% were NEL. ELs exhibited a higher mean Ki67 value (p = 0.025) compared to NEL cases, indicating increased proliferation. No significant correlation was found between EL and NEL with respect to age, gender, tumor site, B-symptoms, LDH levels, or GC/non-GC phenotype. In the present study, out of a total of 131 cases, 29 were classified as EL (22.1%), while 102 cases (77.8%) were classified as NEL. It is recommended to perform IHC to detect expressor status in all cases of DLBCL, as a significant percentage of them may turn out to be ELs, indicating a potentially aggressive clinical course that warrants therapy intensification. Moreover, this IHC panel may serve as a screening tool to identify cases requiring further molecular studies for potential Hit status detection.

Keywords: BCL2; C-MYC; Diffuse large B-cell lymphoma; Double/Triple expressor lymphoma; Double/Triple hit lymphoma; High-grade large B-cell lymphoma; Immunohistochemistry.