Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy and a heterogeneous entity comprised of several biologically distinct subtypes. Recently, novel genetic classifications of DLBCL have been resolved based on common mutational patterns indicative of distinct pathways of transformation. However, the complicated and costly nature of the novel classifiers has precluded their inclusion into routine practice. In view of this, the status of the TP53 gene, which is mutated or deleted in 20–30% of the cases, has emerged as an important prognostic factor for DLBCL patients, setting itself apart from other predictors. TP53 genetic lesions are particularly enriched in a genetic subtype of DLBCL that shares genomic features with Richter Syndrome, highlighting the possibility of a subset of DLBCL arising from the transformation of an occult chronic lymphocytic leukemia-like malignancy, such as monoclonal B-cell lymphocytosis. Patients with TP53-mutated DLBCL, including those with Richter Syndrome, have a particularly poor prognosis and display inferior responses to standard chemoimmunotherapy regimens. The data presented in this manuscript argue for the need for improved and more practical risk-stratification models for patients with DLBCL and show the potential for the use of TP53 mutational status for prognostication and, in prospect, treatment stratification in DLBCL.

Introduction: Hepatitis B virus (HBV) and hepatitis C virus (HCV) represent common infections that are presumably associated with various types of lymphoma and specific clinical features. However, conclusive data are lacking and results from different regional studies are conflicting. Hence, a national study was performed in order to investigate potential associations between hepatitis infections and lymphoma in the Republic of Moldova. Methodology: Data were collected from newly diagnosed adult lymphoma patients from January 2020 to January 2022. Patients who were not tested for HBsAg and anti-HCV and those with an undetermined lymphoma subtype diagnosis were excluded from the study. Subjects with and without viral hepatitis were then evaluated on the basis of clinical and pathological characteristics. Results: One hundred and twenty-nine lymphoma patients were included in the study; 15 (11.6%) patients were diagnosed with hepatitis B, 21 (16.3%) patients with hepatitis C, and 1 (0.78%) patient was positive for both. The majority of hepatitis patients were over 60 years old (62.2%), presented with stage III or IV (81%), had normal lactate dehydrogenase (58.3%) and 0 or 1 extranodal sites (78.4%). The most common lymphoma subtypes were diffuse large B-cell lymphoma (64.9%) and marginal zone lymphoma (8.1%). We did not find any statistically significant differences between infected and uninfected lymphoma patients in regards to clinical features, specific lymphoma subtypes, and presence and location of extranodal involvement. Conclusions: Presence of hepatitis B or C virus infections is not associated with specific clinical and pathological features in Moldovan lymphoma patients.

Introduction. Follicular lymphoma (FL) is a slow-growing B-cell lymphoma with a generally favorable prognosis. Nevertheless, its clinical course is heterogeneous, with a significant subset of patients experiencing early progression or histological transformation into diffuse large B-cell lymphoma (DLBCL), both considered to be high-risk events associated with treatment resistance and markedly inferior outcomes. Importantly, clinical risk factors have limited value in predicting these complications. This review outlines the key biologic features of FL, discussing how the novel molecular biology approaches can explain the clinical heterogeneity and high-risk disease evolution of FL. Materials and methods. A focused literature review was conducted using the PubMed/MEDLINE database to identify studies on follicular lymphoma and its histological transformation to diffuse large B-cell lymphoma. Priority was given to original research or review articles investigating genetic, epigenetic, transcriptional, or microenvironmental determinants of FL. Results. Evidence from early cytogenetic and DNA sequencing studies established BCL2 deregulation as an initiating lesion in FL, with further genetic alterations in epigenetic regulators like KMT2D, EZH2, CREBBP/EP300 occurring early on and persisting throughout the disease course. Studies of transformed FL samples indicate that aggressive evolution is associated with acquisition of additional genetic lesions, such as those affecting the cell cycle regulators CDKN2A/2B and TP53. More recently, integrated genomic, transcriptomic and spatial resolved techniques have demonstrated substantial transcriptional heterogeneity within individual genetic subclones, suggesting that the genotype alone does not determine the phenotype of the malignant cells and supporting a pathogenetic model in which clinical trajectories reflect the combined effects of genomic evolution, transcriptional cell state, and tumor-microenvironment crosstalk. Important findings, including greater infiltration with LAG3+CD8+ T cells in cases of histological transformation to DLBCL and upregulation of transcriptional programs that promote stromal expansion and B-cell receptor signaling in cases of early FL relapse, indicate that integrated profiling represents a promising avenue for identifying the biomarkers and treatment targets that are specific to high-risk disease. Conclusions. Continued research concentrated on multiomic profiling of both malignant and non-malignant tumor compartments is essential in order to reveal the mechanisms of FL heterogeneity and translate these data into practical biomarkers and therapeutic strategies.

Title: A Case of Relapsed Acute Myeloid Leukemia Mimicking Acute Otomoastoiditis

Key Clinical Message: Identifying myeloid sarcoma in rare locations is a diagnostic challenge and requires careful evaluation. The optimal management of extramedullary disease requires further investigation, but tissue biopsy and a personalized approach are crucial. Herein, we describe an unusual case of acute myeloid leukemia presenting with an isolated involvement of the temporal bone after a complete remission of systemic disease for more than a year. The clinical, radiological, and pathological features are discussed, highlighting the importance of considering differential diagnoses and appropriate management.