Since the introduction of rituximab in the late 1990s, significant progress has been made in advancing targeted therapies for B cell lymphomas, improving patients’ chance of being cured and clinicians’ therapeutic armamentarium. A better understanding of disease biology and pathogenic pathways, coupled with refinements in immunophenotypic and molecular diagnostics, have been instrumental in these achievements. While traditional chemotherapy remains fundamental in most cases, concerns surrounding chemorefractoriness and cumulative toxicities, particularly the depletion of the hemopoietic reserve, underscore the imperative for personalized treatment approaches. Integrating targeted agents, notably monoclonal antibodies, alongside chemotherapy has yielded heightened response rates and prolonged survival. A notable paradigm shift is underway with innovative-targeted therapies replacing cytotoxic drugs, challenging conventional salvage strategies like stem cell transplantation. This review examines the landscape of emerging targets for lymphoma cells and explores innovative therapies for diffuse large B cell lymphoma (DLBCL). From Chimeric Antigen Receptor-T cells to more potent monoclonal antibodies, antibody–drug conjugates, bispecific antibodies, checkpoint inhibitors, and small molecules targeting intracellular pathways, each modality offers promising avenues for therapeutic advancement. This review aims to furnish insights into their potential implications for the future of DLBCL treatment strategies.

EUS-FNB has been introduced in clinical practice as a less invasive diagnostic approach with respect to surgery. We performed a single-center retrospective study on the diagnostic efficacy of EUS-guided FNB, including 171 patients with lymph nodes, splenic, and extranodal lesions that underwent EUS for FNB at our institution. Excluding 12 patients who did not undergo FNB and 25 patients with a previous diagnosis of a solid tumor, we included 134 patients with clinical/radiological suspect of a lymphoproliferative disease, including 20 patients with a previous history of lymphoma. Out of the 134 biopsies, material of diagnostic quality was obtained in 111 procedures (84.3%). Histological examination of the EUS-FNB samples produced an actionable diagnosis in 100 cases (74.6%). Among the patients without an actionable diagnosis, a second, different diagnostic procedure produced a further eight diagnoses of lymphoma. Therefore, the sensitivity of EUS-FNB for diagnosing lymphomas was calculated to be 86.4% (51/59). Assignment of lymphomas to WHO classification subtypes was possible in 47/51 (92%) of the cases. In conclusion, EUS-FNB is an effective procedure for the histological characterization of lesions that are suspected to be lymphoproliferative disease, allowing for an actionable diagnosis in 75% of cases.

Background: CD79b is a B-cell-specific antigen that is crucial to the B-cell receptor and is considered a key target for treatment in aggressive B-cell lymphomas. Methods: While immunohistochemical studies have shown widespread expression of CD79b in mature B-cell-derived lymphomas, flow cytometry allows for precise measurement and differentiation between surface and intracellular localization. Results: In our comparative analysis, we discovered that CD79b expression percentages and mean fluorescence intensity (MFI) were lower in a group of 127 cases of aggressive B-cell lymphomas compared to a control group of benign reactive hyperplasia. We also observed significant variability in the surface expression of CD79b among lymphoma cases, with 18% showing predominantly intracellular positivity. There was a strong correlation between the surface expression of CD79b and clonal light chains. Notably, primary mediastinal B-cell lymphomas exhibited significantly lower surface CD79b expression compared to other lymphoma subtypes (median 0.8% IQR 0–48.5 vs. 80% IQR 24–97, p = 0.0005). Furthermore, patients over 60 years old and those with a higher Revised International Prognostic Index (R-IPI) had significantly higher CD79b expression, both of which are associated with a significant benefit from adding an anti-CD79b drug conjugate to first-line chemotherapy in diffuse large B-cell lymphomas. Conclusions: In conclusion, the quantitative flow cytometric analysis of CD79b surface expression in aggressive B-cell lymphomas provides clinically relevant information, highlighting its potential usefulness in guiding therapeutic decisions.

Background and Clinical Significance: This case report describes a 46-year-old male with no prior comorbidities who developed progressive neurological symptoms—ataxia and diplopia—shortly after the second Comirnaty (Pfizer-BioNTech) COVID-19 vaccine dose. The aim is to highlight the diagnostic challenges of central nervous system-dominant hemophagocytic lymphohistiocytosis (HLH) and its overlap with neuroinflammatory disorders. Case Presentation: Initial MRI showed demyelinating lesions in the brain and spinal cord, suggesting acute disseminated encephalomyelitis (ADEM). The patient had only transient improvement with corticosteroids and then multiple relapses with expanding CNS lesions despite cyclophosphamide, plasmapheresis, and rituximab. After 27 months, systemic features appeared, including fever, cytopenias, elevated inflammatory markers, and splenomegaly. Bone marrow analysis revealed hemophagocytosis, fulfilling HLH-2004 criteria, with an H-score of 200 supporting secondary HLH. Given consanguinity and persistent immune activation, next-generation sequencing identified two homozygous PRF1 variants—one pathogenic (p.Arg232His) and one of uncertain significance (p.Ala91Val)—consistent with autosomal recessive familial type 2 HLH. The patient underwent matched unrelated donor hematopoietic stem cell transplantation (HSCT) 11 months after HLH diagnosis, achieving initial stabilization, but ultimately died from infectious complications in March 2025 without evidence of HLH relapse. Conclusions: This case illustrates an atypical adult-onset presentation of familial HLH manifesting primarily with recurrent neuroinflammatory symptoms that initially mimicked ADEM. The diagnostic delay reflects the challenge of recognizing CNS-dominant HLH, especially in adults and in the absence of early systemic features. The identification of biallelic PRF1 variants confirmed an underlying genetic predisposition. This is the first reported case of adult-onset familial HLH presenting predominantly with neurological symptoms following COVID-19 vaccination. The case emphasizes the need to consider genetic forms of HLH in relapsing neuroinflammatory disorders and raises the hypothesis that vaccination may unmask subclinical immune dysregulation in genetically susceptible individuals