Pathological Insights into the Subclassification of Diffuse Large B-Cell Lymphoma (NOS)
Authors: Girgis Boctor Mary Louis Labib , Salman Manal Ibrahim , Mohamed Abd El Khalek Safaa Mahmoud , Halim Ibrahim Mariam Ibrahim 
Published: November 2024

Abstract

Introduction
Diffuse Large B-cell Lymphoma, NOS represents around 25-35% of adult Non- Hodgkin’s lymphoma worldwide. According to the 5th edition of WHO for Hematolymphoid neoplasms, DLBCL, NOS encompasses all biologically heterogeneous cases with no clear criteria for inclusion in a specific diagnostic category. The sixth and seventh decade are reported as the median age for DLBCL, NOS in developed countries and a lower median age in developing countries, with slight male predominance (1.2:1). DLBCL, NOS is further subclassified according to cell of origin (COO) using gene expression profiling (GEP) and various immunohistocehmical (IHC) algorithms into germinal center (GCB) and activated B-cell (ABC) subtypes, which carries a prognostic and therapeutic value.

Objectives
In our study, we have recorded and compared the demographic and pathological data of the DLBCL, NOS subtypes in Ain Shams University Hospitals over the period of three years.

Materials and Methods
Our retrospective study was conducted in the Department of Histopathology in Ain Shams University Hospitals from January 2020 till December 2022. We retrieved all available cases with a diagnosis consistent with DLBCL, NOS over the period of these three years. A total of 102 cases with available reports, H&E slides and paraffin blocks with sufficient tissue material were included in this study. We recorded the demographic and pathological data of the cases, re-examined available H& E and IHC slides, and applied immunohistochemical (IHC) staining of CD10, and multiple myeloma oncogene 1(MUM1) to remaining DLBCL cases with available paraffin blocks and sufficient tissue material for further subclassification of into GCB and ABC subtypes according to the Hans and modified Hans immuoalgorithms. Finally, we compared and analyzed the demographic and pathological data of both subtypes.

Results
DLBCL, NOS represented 35.3 % of all NHL cases and 26.19% of all lymphoma cases overall. Out of 102 cases of DLBCL, NOS, 38.2% were GCB while were 61.8 % ABC subtypes. The median age for DLBCL, NOS was 54.9 with male to female ratio of 1.3:1. The ABC subtype showed a higher median age and female affection predominance as compared to GCB. The most affected site overall was the cervical nodal group while stomach, spleen and liver were reported as the most commonly involved extranodal sites. The ABC subtype showed significant association with extra-abdominal nodal groups as compared to the GCB subtype (P = 0.02). The mean Ki-67 proliferation index for DLBCL, NOS was 70.42% while the ABC subtype exhibited higher Ki-67 index with a mean of 74.21 as compared to the GCB subtype with a mean of 69.1 (P = 0.08). A higher proportion of cases of the ABC subtype exhibited &gt;70 % ki-67 proliferation index than the GCB subtype (P = 0.08). Tumor necrosis was noted in 34.8% of cases overall, with higher proportion of cases belonging to the ABC subtype (P = 0.45). Moreover, centroblastic morphological variant was the most common histology reported in both subtypes with less common histological features/variants observed in the ABC subtype; immunoblastic and anaplastic variants.

Conclusion
In conclusion, incidence of DLBCL, NOS in Ain Shams university hospitals was closely similar to recorded international incidence. According to COO, the ABC subtype was more frequent than the GCB subtype. The ABC subtype was associated with more nodal involvement with a significant predilection to extra- abdominal nodal groups. Moreover, the ABC subtype reported higher overall ki-67 proliferation index with more proportion of cases with &gt; 70% proliferation index and more advanced histological features: immunoblastic/anaplastic variants and necrosis.