11 Clinicopathological and molecular analysis of diffuse large B cell lymphoma:A retrospective study of 23 cases with focus on genetic alterations and prognostic markers

Context Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous and aggressive malignancy with varied clinical presentations, molecular features, and prognostic factors. This retrospective study aimed to analyze 23 distinct DLBCL cases, emphasizing common clinical, molecular, and genetic characteristics, especially in the elderly female population. Design A cohort of 23 DLBCL patients was retrospectively reviewed, with 72% being elderly females over 70 years. Accurate diagnosis was confirmed through histology, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and B-cell rearrangement studies. The cell origin classification of dividing DLBCL into germinal center type (GCB) or activated b cell type (ABC) was used based on IHC expression of CD10, BCL6 and MUM-1/IRF4. Results The most frequent and prominent anatomic locations were cervical lymph nodes and retroperitoneal masses. MYC, BCL2, and BCL6 rearrangements were identified in four 17.4 %(4/23) , 17.4%(4/23) and 21.7%(5/23) cases, respectively. A rare and remarkable case of triple-hit lymphoma was observed in a 3-year-old female, exhibiting rearrangements in all three genes. One case of DLBCL-ABC type was found to have MYD88 p.L268P mutation along with CD79B mutation,B lymphocyte induced maturation protein-1 (BLIPM-1) mutation and CDKN2A deletion. Poor prognostic markers, including biallelic TP53 mutations, CDK2A deletions and MYC rearrangement with BCL2 /BCL6 translocations were detected in select cases. Additionally, eight cases showed no conventional DLBCL FISH panel aberrations, highlighting significant genetic and molecular diversity. Conclusion This study underscores the remarkable molecular complexity and clinical heterogeneity of DLBCL, particularly in elderly females. It highlights the critical importance of advanced and comprehensive diagnostic techniques, such as FISH, NGS, and B-cell rearrangement studies. The identification of triple-hit lymphoma and the mutational prognostic markers emphasises the need for an accurate and nuanced diagnostic approach. Furthermore, the detection of prognostic markers significantly influences the therapeutic strategy and clinical outcomes.. The absence of conventional FISH panel aberrations demonstrates the considerable genetic diversity of DLBCL.