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Abstract Background c-MYC and BCL2 positivity are important prognostic factors for diffuse large B-cell lymphoma. However, manual quantification is subject to significant intra- and inter-observer variability. We developed an automated method for quantification in whole-slide images of tissue sections where manual quantification requires evaluating large areas of tissue with possibly heterogeneous staining. We train this method using annotations of tumor positivity in smaller tissue microarray cores where expression and staining are more homogeneous and then translate this model to whole-slide images. Methods Our method applies a technique called attention-based multiple instance learning to regress the proportion of c-MYC-positive and BCL2-positive tumor cells from pathologist-scored tissue microarray cores. This technique does not require annotation of individual cell nuclei and is trained instead on core-level annotations of percent tumor positivity. We translate this model to scoring of whole-slide images by tessellating the slide into smaller core-sized tissue regions and calculating an aggregate score. Our method was trained on a public tissue microarray dataset from Stanford and applied to whole-slide images from a geographically diverse multi-center cohort produced by the Lymphoma Epidemiology of Outcomes study. Results In tissue microarrays, the automated method had Pearson correlations of 0.843 and 0.919 with pathologist scores for c-MYC and BCL2, respectively. When utilizing standard clinical thresholds, the sensitivity/specificity of our method was 0.743 / 0.963 for c-MYC and 0.938 / 0.951 for BCL2. For double-expressors, sensitivity and specificity were 0.720 and 0.974. When translated to the external WSI dataset scored by two pathologists, Pearson correlation was 0.753 & 0.883 for c-MYC and 0.749 & 0.765 for BCL2, and sensitivity/specificity was 0.857/0.991 & 0.706/0.930 for c-MYC, 0.856/0.719 & 0.855/0.690 for BCL2, and 0.890/1.00 & 0.598/0.952 for double-expressors. Survival analysis demonstrates that for progression-free survival, model-predicted TMA scores significantly stratify double-expressors and non double-expressors (p = 0.0345), whereas pathologist scores do not (p = 0.128). Conclusions We conclude that proportion of positive stains can be regressed using attention-based multiple instance learning, that these models generalize well to whole slide images, and that our models can provide non-inferior stratification of progression-free survival outcomes.

Introduction: Neurological toxicity following chimeric antigen receptor T-cell infusion, termed immune cell-associated neurotoxicity syndrome (ICANS), is a common and limiting factor in the expansion of this promising treatment modality. While refractory cases of ICANS have been reported in clinical trials, there is limited description of these presentations and their associated treatment. The use of predictive biomarkers and risk stratification tools offer a means of identifying patients with higher likelihood of developing ICANS; however, their discriminatory sensitivity has been shown to vary depending on disease type. Case Presentation: In this case report, we present the clinical course of a patient with diffuse large B-cell lymphoma treated with axicabtagene ciloleucel who developed a nonsinusoidal pattern of severe neurotoxicity refractory to steroid treatment, and we evaluate the predictive value of commonly used biomarkers and risk scores in assessing the likelihood of her presentation. Conclusion: In assessing the efficacy of these scores in the context of our patient’s pattern of severe neurotoxicity exacerbations, we aim to provide valuable clinical insight to better manage refractory ICANS and ultimately improve patient outcomes.

Abstract Background The molecular diversity exhibited by diffuse large B-cell lymphoma (DLBCL) is a significant obstacle facing current precision therapies. However, scoring using the International Prognostic Index (IPI) is inadequate when fully predicting the development of DLBCL. Reprogramming lipid metabolism is crucial for DLBCL carcinogenesis and expansion, while a predictive approach derived from lipid metabolism-associated genes (LMAGs) has not yet been recognized for DLBCL. Methods Gene expression profiles of DLBCL were generated using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The LASSO Cox regression was used to construct an effective predictive risk-scoring model for DLBCL patients. The Kaplan-Meier survival assessment was employed to compare a given risk score with the IPI score and its impact on the survival of DLBCL patients. Functional enrichment examination was performed utilizing the KEGG pathway. After identifying hub genes via single-sample GSEA (ssGSEA), immunohistochemical staining and immunofluorescence were performed on lymph node samples from control and DLBCL patients to confirm these identified genes. Results Sixteen lipid metabolism- and survival-associated genes were identified to construct a prognostic risk-scoring approach. This model demonstrated robust performance over various datasets and emerged as an autonomous risk factor for predicting the development of DLBCL patients. The risk score could significantly distinguish the development of DLBCL patients from the low-risk and elevated-risk IPI classes. Results from the inhibitory immune-related pathways and lower immune scores suggested an immunosuppressive phenotype within the elevated-risk group. Three hub genes, MECR, ARSK, and RAN, were identified to be negatively correlated with activated CD8 T cells and natural killer T cells in the elevated-risk score class. Ultimately, it was determined that these three genes were expressed by lymphoma cells but not by T cells in clinical samples from DLBCL patients. Conclusion The risk level model derived from 16 lipid metabolism-associated genes represents a prognostic biomarker for DLBCL that is novel, robust, and may have an immunosuppressive role. It can compensate for the limitations of the IPI score in predicting overall survival and has potential clinical application value.

Diffuse large B-cell lymphoma is one of the most frequent mature B-cell hematological neoplasms and non-Hodgkin lymphomas. Despite advances in diagnosis and treatment, clinical evolution is unfavorable in a subset of patients. Using molecular techniques, several pathogenic models have been proposed, including cell-of-origin molecular classification; Hans’ classification and derivates; and the Schmitz, Chapuy, Lacy, Reddy, and Sha models. This study introduced different machine learning techniques and their classification. Later, several machine learning techniques and artificial neural networks were used to predict the DLBCL subtypes with high accuracy (100–95%), including Germinal center B-cell like (GCB), Activated B-cell like (ABC), Molecular high-grade (MHG), and Unclassified (UNC), in the context of the data released by the REMoDL-B trial. In order of accuracy (MHG vs. others), the techniques were XGBoost tree (100%); random trees (99.9%); random forest (99.5%); and C5, Bayesian network, SVM, logistic regression, KNN algorithm, neural networks, LSVM, discriminant analysis, CHAID, C&R tree, tree-AS, Quest, and XGBoost linear (99.4–91.1%). The inputs (predictors) were all the genes of the array and a set of 28 genes related to DLBCL-Burkitt differential expression. In summary, artificial intelligence (AI) is a useful tool for predictive analytics using gene expression data.

The gut microbiome (GMB) has been extensively reported to be associated with the development and prognosis of human diseases. This study aims to investigate the relationship between GMB composition and chemotherapy efficacy in diffuse large B-cell lymphoma (DLBCL). We demonstrated that DLBCL patients at diagnosis have altered GMB compositions. Significant enrichment of the Proteobacteria phylum in DLBCL patients was observed. Gene analysis showed a high abundance of virulence factors genes. We found baseline GMB to be associated with clinical outcomes. The emergence of Lactobacillus fermentum was correlated with better treatment outcome. Our pilot results suggested a correlation between GMB composition and DLBCL development and prognosis. Clues from our study, together with previous research, provided a rational foundation for further investigation on the pathogenesis, prognosis value, and targeted therapy of GMB in DLBCL.

Background: Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy remains the standard of first-line treatment for diffuse large B-cell lymphoma (DLBCL). Up to 40% of DLBCL is characterized by relapse and refractory after treatment. Preliminary study reported Hypoxia-inducible factor-1a (HIF-1a) overexpression in 88.5% of DLBCL tumors in the Dr. Kariadi Hospital. Moreover, the role of hypoxia and HIF-1a has previously never been explored in DLBCL. Objectives: To evaluate the effect of hypoxia modulation to increased chemotherapeutic response in DLBCL. Methods: Single blind randomized control study was performed, with pre-test and post-test control group design. Research sampling consisted of DLBCL patients. The inclusion criteria include newly diagnosed DLBCL with HIF-1a overexpression and randomized to receive hypoxia modulation consisting of carbogen inhalation and nicotinamide administration, before R-CHOP chemotherapy. The tissue biopsy, histopathology and immunohistochemical studies were done. Chemotherapeutic responses were evaluated after 10-14 days following the first cycle of R-CHOP chemotherapy. Results: Out of twenty-six DLBCL participants with HIF-1a overexpression, there were 20 participants who completed the research protocol: 10 participants each in the intervention and control group. Demographic, clinicopathological, laboratory and disease characteristics were not statistically different between the two research groups (p>0.05). Baseline tumor volume to be evaluated was also considered equal (172.3 cm3 vs. 152.8 cm3 , p=0.597). Following the carbogen inhalation and nicotinamide administration, serum HIF-1a and lactate reduction can be observed. There was also a significant tumor volume shrinkage in both the intervention and control (mean -85.7 cm3 vs. -118.27 cm3 ) group, though the reduction was not statistically different (Delta 58.85% vs. 65.63%, p=0.474). Conclusion: The addition of hypoxia modulation to R-CHOP chemotherapy for DLBCL has shown beneficial effects on both serum HIF-1a and lactate concentration. However, the benefits did not correlate to increase a better tumor response compared to the control group.

Background. Coronavirus disease (COVID-19), caused by SARS-CoV-2, presents new challenges to hematologists, highlighting the vulnerability of patients with hematological malignancies, in particular with diffuse large B-cell lymphoma (DLBCL). Identification of hospital mortality risk factors is necessary for subsequent stratification of patients into risk groups, which will allow further risk-based therapy.Aim. To develop a prognostic model and identify risk factors for hospital mortality in patients with DLBCL associated with COVID-19.Materials and methods. The interim retrospective study included 112 patients with an immunohistochemically confirmed diagnosis of DLBCL, coronavirus infection verified based on polymerase chain reaction (PCR) for SARS-CoV-2, and viral pneumonia associated with COVID-19. To determine the risk factors for hospital mortality, a multivariate (logistic regression) statistical analysis was performed. The study end point was a binary variable - the patient vital status (discharged alive or died).Results and conclusion. Of the 112 patients, 24 died. Due to the limited number of patients compared to the number of predictors and to avoid overfitting, a two-stage approach to constructing a predictive model was used. In univariate analysis, statistically significant during hospitalization were the hematological disease status (complete remission/partial remission, progression/relapse, de novo), positive PCR result, C-reactive protein level >6 mg/L, platelets 248 U/L, D-dimer >500 ng/mL and the degree of lung tissue damage according to computed tomography >50 % (grade II and above), respiratory failure I degrees and higher. The final model was constructed by minimizing the Akaike information criterion. The final model included a positive PCR result, stage II respiratory failure, hematologic disease status (relapse/progression), and albumin level at the time of hospital admission.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin’s lymphoma, characterized by its aggressive nature and heterogeneity. Despite significant advances in understanding DLBCL pathogenesis, there is still a need to elucidate the intricate mechanisms involved in disease progression and identify novel therapeutic targets. Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as crucial mediators of intercellular communication in various physiological and pathological processes, including cancer. In recent years, evidence has suggested that EVs play a vital role in DLBCL biology by facilitating the exchange of genetic material, especially miRNAs, and proteins and lipids between tumor cells, immune cells, and the tumor microenvironment. We summarize and discuss the biological functions of EVs in DLBCL and their effects on the tumor microenvironment, highlighting their influence on DLBCL pathobiology, immune evasion, angiogenesis, and drug resistance. We also investigated EVs’ diagnostic and prognostic potential as circulating biomarkers in DLBCL, emphasizing their utility in the non-invasive monitoring of the disease status and treatment response. Understanding the complex interplay between EVs and DLBCL may open up new avenues for personalized medicine, improve patient stratification, and facilitate the development of innovative therapeutic interventions in this devastating hematological malignancy.

In this comprehensive review, we delve into the transformative role of artificial intelligence (AI) in refining the application of multi-omics and spatial multi-omics within the realm of diffuse large B-cell lymphoma (DLBCL) research. We scrutinized the current landscape of multi-omics and spatial multi-omics technologies, accentuating their combined potential with AI to provide unparalleled insights into the molecular intricacies and spatial heterogeneity inherent to DLBCL. Despite current progress, we acknowledge the hurdles that impede the full utilization of these technologies, such as the integration and sophisticated analysis of complex datasets, the necessity for standardized protocols, the reproducibility of findings, and the interpretation of their biological significance. We proceeded to pinpoint crucial research voids and advocated for a trajectory that incorporates the development of advanced AI-driven data integration and analytical frameworks. The evolution of these technologies is crucial for enhancing resolution and depth in multi-omics studies. We also emphasized the importance of amassing extensive, meticulously annotated multi-omics datasets and fostering translational research efforts to connect laboratory discoveries with clinical applications seamlessly. Our review concluded that the synergistic integration of multi-omics, spatial multi-omics, and AI holds immense promise for propelling precision medicine forward in DLBCL. By surmounting the present challenges and steering towards the outlined futuristic pathways, we can harness these potent investigative tools to decipher the molecular and spatial conundrums of DLBCL. This will pave the way for refined diagnostic precision, nuanced risk stratification, and individualized therapeutic regimens, ushering in a new era of patient-centric oncology care.

Objective: The purpose of this study is to investigate the correlation between elevated levels of CCAAT/enhancer-binding protein beta (CEBPB) gene expression and unfavorable outcomes in diffuse large B-cell lymphoma (DLBCL). The goal is to elucidate potential therapeutic targets associated with this relationship. Methods: Differential expression and survival analyses were conducted using data from the Gene Expression Omnibus (GEO) database. The functions of CEBPB in DLBCL cells were investigated through cell culture, RNA extraction, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. In addition, a weighted gene co-expression network analysis (WGCNA) was performed to pinpoint gene modules associated with CEBPB. Furthermore, experimental validation was carried out to explore the interaction between CEBPB and interleukin 1 beta (IL1B). Results: High levels of CEBPB expression are prominently observed in DLBCL, with its overabundance significantly linked to the diagnosis of DLBCL. Survival analysis reveals that patients exhibiting elevated CEBPB expression tend to experience a poorer prognosis. Further validation confirmed CEBPB's role in promoting DLBCL cell proliferation and cell cycle progression. WGCNA identified CEBPB-related gene modules, with IL1B identified as a potential regulatory gene of CEBPB. The presence of high levels of IL1B has been correlated with an unfavorable prognosis in individuals diagnosed with DLBCL. Experiments demonstrate that IL1B promotes DLBCL cell proliferation through CEBPB. Conclusions: This study reveals the significant roles of CEBPB and IL1B in DLBCL, providing new theoretical foundations and potential molecular targets for the treatment and prognosis of DLBCL.

Primary lacrimal sac lymphoma is a rare condition, often presenting with nasolacrimal duct obstruction. Herein, we present a unique case of diffuse large B-cell lymphoma (DLBCL) involving the lacrimal sac, maxillary sinus, and infraorbital nerve. Prompt diagnosis via biopsy is essential for timely treatment and the prevention of tumor progression. A 66-year-old female presented with intractable epiphora, infraorbital nerve hypesthesia, and medial canthal swelling. Imaging revealed a soft tissue mass in the right maxillary sinus extending into the right inferior orbit and nasal cavity. A biopsy confirmed DLBCL, prompting systemic chemotherapy. Residual disease prompted high-dose involved-site radiation, resulting in tumor regression. To our knowledge, this is the first case of primary DLBCL of the lacrimal sac with concurrent involvement of the maxillary sinus and infraorbital nerve. This case underscores the significance of lacrimal sac biopsy in refractory dacryocystitis or unilateral sinus disease and the effectiveness of multimodal treatment approaches in managing DLBCL. [ABSTRACT FROM AUTHOR]

The standard treatment for Diffuse Large B-Cell Lymphoma (DLBCL) is rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). However, many patients require subsequent treatment after relapsed disease. The ABC subtype of DLBCL (ABC-DLBCL) has a worse prognosis, and the PHOENIX trial explored adding ibrutinib to RCHOP for this patient population. The trial showed favorable outcomes for younger patients, and our study aimed to inform clinical decision-making via a cost-effectiveness model to compare RCHOP with and without ibrutinib (I-RCHOP). A Markov decision analysis model was designed to compare the treatments for patients younger than 60 years with ABC-DLBCL. The model considered treatment pathways, adverse events, relapses, and death, incorporating data on salvage treatments and novel therapies. The results indicated that I-RCHOP was more cost-effective, with greater quality-adjusted life years (QALY, 15.48 years vs. 14.25 years) and an incremental cost-effectiveness ratio (ICER) of CAD 34,111.45/QALY compared to RCHOP only. Sensitivity analyses confirmed the model’s robustness. Considering the high market price for ibrutinib, I-RCHOP may be more costly. However, it is suggested as the preferred cost-effective strategy for younger patients due to its benefits in adverse events, overall survival, and quality of life. The decision analytic model provided relevant and robust results to inform clinical decision-making.

Abstract Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is considered for patients with high‐risk B‐cell lymphoma and relapsed or refractory disease. This study aimed to analyze the long‐term follow‐up data of patients who underwent allo‐HSCT in Taiwan. This was a retrospective observational study using data from the Taiwan Society of Blood and Marrow Transplantation database. A total of 105 patients who underwent allo‐HSCT because of high‐risk, relapsed, or refractory disease between 2010 and 2019 were included. Forty‐five percent of the patients previously underwent autologous stem cell transplantation (ASCT). The median follow‐up duration was 18.6 months. The probability of 3‐year progression‐free survival and overall survival (OS) was 34.5% and 37%, respectively. The probability of 1‐year non‐relapse mortality was 31.4%, and the major cause was infection (75.8%). The multivariable analysis showed that not in remission at the time of transplantation and the absence of graft‐versus‐host disease (GVHD) were factors associated with inferior OS. The probability of 3‐year OS in patients with diffuse large B‐cell lymphoma who underwent allo‐HSCT and allo‐HSCT after ASCT was 40.2% and 25.2%, respectively. Allo‐HSCT could be a salvage therapeutic option for relapsed or refractory B‐cell lymphoma. Complete remission at the time of allo‐HSCT and the presence of GVHD are independent variables for overall survival.

Lymphoma is a heterogeneous group of lymphocyte malignancies that may involve lymphatic tissue, bone marrow, or extranodal sites. The lecture provides a brief overview of the current state of the problem of diagnosis and treatment of primary testicular lymphoma. Primary testicular lymphoma (PTL) is a rare lymphoid malignancy. Though it is rare, PTL is the most common type of testicular tumor in men over 60 years of age. The most common histological type is diffuse large B-cell lymphoma. To date, there are no well-documented etiological or risk factors for PTL. In contrast to other common testicular neoplasms, there was no statistically significant association of PTL with cryptorchidism, trauma, chronic orchitis, or infertility. Ultrasound is generally the first-line imaging method used to characterize testicular lesions. PTL manifests itself in the form of a hypoechoic formation, which can take the form of either a single large formation or multiple small formations that occupy most of the testicular parenchyma or completely replace it. Systemic treatment, including orchiectomy, chemotherapy, radiation therapy, and intrathecal prophylaxis, is necessary for all patients with PTL. In addition to achieving complete remission, the goal of PTL treatment is to prevent recurrences in the contralateral testis and central nervous system. The presented information is supplemented by our own observation and images. Personal medical data is published with the written consent of the patient. In our case, the patient’s age was 38 years, which does not fall into the specified age group for primary testicular lymphoma. In our opinion, the publication of this clinical case and analysis of scientific literature on this topic are relevant.

Background/Aims Although rituximab, an antiCD20 monoclonal antibody, has dramatically improved the clinical outcomes of diffuse large B-cell lymphoma, rituximab resistance remains a challenge. Methods We developed a rituximab-resistant cell line (RRCL) by sequential exposure to gradually increasing concentrations of rituximab in a rituximab-sensitive cell line (RSCL). When the same dose of rituximab was administered, RRCL showed a smaller decrease in cell viability and apoptosis than RSCL. To determine the differences in gene expression between RSCL and RRCL, we performed next-generation sequencing. Results In total, 1,879 differentially expressed genes were identified, and in the over-representation analysis of Consensus-PathDB, mitogen-activated protein kinase (MAPK) signaling pathway showed statistical significance. MAPK13, which encodes the p38δ protein, was expressed more than four-fold in RRCL. Western blot analysis revealed that phosphop38 expression mainwas increased in RRCL, and when p38 inhibitor was administered, phosphop38 expression was significantly decreased. Therefore, we hypothesized that p38 MAPK activation was associated with rituximab resistance. Previous studies have suggested that p38 is associated with NF-κB activation. Deferasirox has been reported to inhibit NF-κB activity and suppress phosphorylation of the MAPK pathway. Furthermore, it also has cytotoxic effects on various cancers and synergistic effects in overcoming drug resistance. In this study, we confirmed that deferasirox induced dose-dependent cytotoxicity in both RSCL and RRCL, and the combination of deferasirox and rituximab showed a synergistic effect in RRCL at all combination concentrations. Conclusions We suggest that p38 MAPK, especially p38δ, activation is associated with rituximab resistance, and deferasirox may be a candidate to overcome rituximab resistance.

Abstract A 66‐year‐old woman who had received tacrolimus for more than 11 years was admitted with high fever, generalized lymphadenopathy, and persistent gastrointestinal bleeding. Histopathological evaluation of the lymph nodes and colonic mucosa confirmed the diagnosis of Epstein–Barr virus‐positive diffuse large B‐cell lymphoma. After discontinuation of tacrolimus, the lymphoma did not improve, and low‐dose chemotherapy was introduced, which resulted in a recovery of lymphocyte counts and induction of complete remission. Low‐dose anticancer treatments that suppress tumor growth while awaiting normal lymphocyte recovery for several weeks may be a useful therapeutic option even for aggressive lymphomas that develop during immunosuppressant therapy.

Malignant lymphoma has various pulmonary manifestations on chest CT, including nodules, masses, areas of consolidation, and ground-glass opacity. These presentations can pose a diagnostic challenge, as they mimic other disease patterns. Herein, we report a case of diffuse large B-cell lymphoma (DLBCL) manifesting as miliary nodules in a 67-year-old male initially presenting with dyspnea and fever. Radiologic findings included diffuse, bilateral, multiple tiny nodules consistent with metastasis, miliary tuberculosis, and fungal infection. However, further investigations, including laboratory tests, imaging, and biopsies, led to the diagnosis of DLBCL involving the lungs. Herein we reported a rare case of lymphoma involvement of the lung presenting as miliary nodules. Accurate diagnosis relies on a comprehensive evaluation of the clinical history, physical features, laboratory test results, and imaging findings.

Abstract Background 18F-FDG PET/CT provides precise information about dissemination of lymphoma lesions. Dmax, defined as distance between the two lesions that were farthest apart by PET/CT, was found to be a promising predictor of Diffuse large B-cell lymphoma (DLBCL) outcome in a small size of clinical trial data. We analyzed the impact of Dmax on the outcome of a large real-world DLBCL cohort. Methods Data of newly diagnosed DLBCL at the Third Affiliated Hospital of Soochow University were retrospectively collected. Baseline Dmax, clinical data and survival information were recorded. A metabolic parameter, metabolic bulk volume (MBV), was also measured to verify the independent impact of Dmax. Results Optimal cut-off values for Dmax and MBV were 45.34 cm and 21.65 cm3. With a median follow-up of 32 months, Dmax significantly impacted progression-free survival (PFS) and overall survival (OS) in 253 DLBCL patients. For Dmaxlow and Dmaxhigh groups, estimated 3-year OS were 87.0% and 53.8% (p

Objective To investigate the correlation between ITPKB mutation's variant allele frequency (VAF) and prognosis of diffuse large B-cell lymphoma (DLBCL). Methods This study included 155 patients with DLBCL initially diagnosed in the People's Hospital of Xinjiang Uygur Autonomous Region from June 2014 to December 2020. Paraffin-embedded tumor tissue specimens were obtained, and tumor tissue DNA was extracted. A total of 475 hotspot genes including ITPKB were detected by the next generation sequencing to analyze the relationship of the VAF of high-frequency mutant gene with progression-free survival (PFS) and overall survival (OS). Results The mutation frequency of ITPKB was 18.71%. The PFS was significantly shorter in the patients with ITPKB mutations than in those without mutations (37 months vs. 108 months; HR=1.643, 95%CI: 0.920-2.934, P=0.093). The R-language based web tool was used to find the best VAF cutoff to differentiate prognosis. The patients were divided into two groups (VAF High vs. VAF Low+Wt) according to their VAF values. The optimal VAF threshold for ITPKB was 27.48% (HR=3.480, 95%CI: 1.70-7.13, P=0.00027). Multivariate Cox analysis was conducted using clinical indicators such as age, gender, COO classification, IPI, and LDH, and the results showed that PFS was associated with high ITPKB VAF (≥28%) (HR=3.592, 95%CI: 1.738-7.425, P < 0.001) which was an independent adverse predictor of PFS. Conclusion The high load of ITPKB mutation is an independent risk factor for the PFS of patients with DLBCL, and the VAF of ITPKB mutation has a prognostic predictive value for patients with DLBCL.

Diffuse large B-cell lymphoma (DLBCL) and angioimmunoblastic T-cell lymphoma (AITL) are two subtypes of non-Hodgkin lymphoma (NHL). The simultaneous occurrence of DLBCL and AITL in a composite lymphoma is very rare, and there are no established treatment regimens. We present the case of an 85-year-old male admitted to the intensive care unit with distributive shock, lymphocytosis, and lymphadenopathy, who was subsequently diagnosed with composite AITL and DLBCL, and treated with brentuximab vedotin (BV) and rituximab. To our knowledge, this is the first case of composite lymphoma presenting with distributive shock and treated with BV and rituximab, with successful resolution of shock.

Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common histopathological type of non-Hodgkin's lymphoma and might arise from various extranodal sites. Little is known about the clinical characteristics and survival outcomes of primary DLBCL of the brain, including the cerebrum, cerebellum, brain steam and ventricle (CCSV). Thus, we performed this study to explore the independent prognostic factors of CCSV-DLBCL using the Surveillance, Epidemiology, and End Results (SEER) database. Materials and methods: We extracted the data of patients diagnosed with CCSV-DLBCL between 1975 and 2016 from the SEER database. Variables including demographic characteristics, Ann Arbor stage and therapies, such as surgery, radiation and chemotherapy, were all collected. The prognostic factors on overall survival (OS) and disease-specific survival (DSS) were analysed using Kaplan–Meier curves. Results: One thousand three hundred and twenty-eight patients were finally enrolled in the analysis. The median age was 62 years old. More than half of the cases of CCSV-DLBCL (54.22%) originated from the cerebrum. Patients older than 75 years had the worst OS and DSS. Moreover, black people had the worst survival outcomes compared with white and other people. Surgery, radiation and chemotherapy all significantly improved OS and DSS. Conclusion: To the best of our knowledge, this is the largest population-based study of CCSV-DLBCL. Advanced age, black race, lack of surgical resection, radiation or chemotherapy were all poor prognostic factors.

Predicting MYC and BCL2 double-expressor lymphoma prognosis using the system immune-inflammatory index (SII) and prognostic nutritional index (PNI) (DEL). From January 2015 to December 2021, 281 diffuse large B-cell lymphoma (DLBCL) wax blocks were used to make tissue chips. Screening double expressor lymphoma (DEL) instances involved immunocytochemistry and fluorescence in situ hybridization. Academic analysis used clinicopathological characteristics and follow-up data. SII, PNI, and DEL prognosis were correlated using univariate and multivariate cox regression analysis. The median age of 78 DEL patients is 60 (range: 43–74). SII and PNI cut-off values of 603.5, 3.07, and 144 predict PFS and OS well. Lower SII is associated with longer PFS (HR for SII = 0.34, 95% CI 0.15–0.76, P = 0.006; HR for NLR = 0.46, 95% CI 0.22–0.99, P = 0.048; HR for PLR = 0.39, 95% CI 0.17–0.94, P = 0.025; LMR = 0.39, 95%, CI 0.17–0.94, P = 0.025) and OS (HR for SII = 0.16, 95% CI 0.05–0.51, P = 0.005; HR for PNI = 0.20, 95% CI 0.06–0.62, P = 0.002). SII and PNI are promising predictors for twofold expressor DLBCL. Combining these increase prediction accuracy.

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in adults. Standard treatment includes chemoimmunotherapy with R-CHOP or similar regimens. Despite treatment advancements, many patients with DLBCL experience refractory disease or relapse. While baseline 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) parameters have shown promise in predicting survival, they may not fully capture lesion heterogeneity. This study aimed to assess the prognostic value of baseline 18F-FDG PET radiomics features in comparison with clinical factors and metabolic parameters for assessing 2-year progression-free survival (PFS) and 5-year overall survival (OS) in patients with DLBCL. Results A total of 201 patients with DLBCL were enrolled in this study, and 1328 radiomics features were extracted. The radiomics signatures, clinical factors, and metabolic parameters showed significant prognostic value for individualized prognosis prediction in patients with DLBCL. Radiomics signatures showed the lowest Akaike information criterion (AIC) value and highest Harrell’s concordance index (C-index) value in comparison with clinical factors and metabolic parameters for both PFS (AIC: 571.688 vs. 596.040 vs. 576.481; C-index: 0.732 vs. 0.658 vs. 0.702, respectively) and OS (AIC: 339.843 vs. 363.671 vs. 358.412; C-index: 0.759 vs. 0.667 vs. 0.659, respectively). Statistically significant differences were observed in the area under the curve (AUC) values between the radiomics signatures and clinical factors for both PFS (AUC: 0.768 vs. 0.681, P = 0.017) and OS (AUC: 0.767 vs. 0.667, P = 0.023). For OS, the AUC of the radiomics signatures were significantly higher than those of metabolic parameters (AUC: 0.767 vs. 0.688, P = 0.007). However, for PFS, no significant difference was observed between the radiomics signatures and metabolic parameters (AUC: 0.768 vs. 0.756, P = 0.654). The combined model and the best-performing individual model (radiomics signatures) alone showed no significant difference for both PFS (AUC: 0.784 vs. 0.768, P = 0.163) or OS (AUC: 0.772 vs. 0.767, P = 0.403). Conclusions Radiomics signatures derived from PET images showed the high predictive power for progression in patients with DLBCL. The combination of radiomics signatures, clinical factors, and metabolic parameters may not significantly improve predictive value beyond that of radiomics signatures alone.

Abstract Background Tumor-derived extracellular vesicles (EVs) have been proposed as the essential mediator between host immunity and cancer development. These EVs conduct cellular communication to facilitate tumor growth, enable invasion and metastasis, and shape the favorable tumor microenvironment. Lymphoma is one of the most common hematological malignancies in humans and dogs. Effective T-cell responses are required for the control of these malignancies. However, the immune crosstalk between CD8 + T-cells, which dominates anti-tumor responses, and canine lymphoma has rarely been described. Methods This study investigates the immune manipulating effects of EVs, produced from the clinical cases and cell line of canine B cell lymphoma, on CD8 + T-cells isolated from canine donors. Results Lymphoma-derived EVs lead to the apoptosis of CD8 + T-cells. Furthermore, EVs trigger the overexpression of CTLA-4 on CD8 + T-cells, which indicates that EV blockade could serve as a potential therapeutic strategy for lymphoma patients. Notably, EVs transform the CD8 + T-cells into regulatory phenotypes by upregulating their PD-1, PD-L1, and FoxP3 mRNA expression. The regulatory CD8 + T-cells secret the panel of inhibitory cytokines and angiogenic factors and thus create a pro-tumorigenic microenvironment. Conclusion In summary, the current study demonstrated that the EVs derived from canine B cell lymphoma impaired the anti-tumor activity of CD8 + T-cells and manipulated the possible induction of regulatory CD8 + T-cells to fail the activation of host cellular immunity.

Abstract Purpose To investigate the prognosis value of a combined model based on 18F-fluoro-deoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) baseline and interim parameters in patients with diffuse large B-cell lymphoma (DLBCL). Methods We retrospectively analyzed the PET metabolic parameters and clinical data of 154 DLBCL patients between December 2015 and October 2020. All of these patients underwent 18F-FDG PET/CT scan before treatment and after three or four courses of chemotherapy. The optimal cut-off values for quantitative variables were determined by the receiver operating characteristic (ROC) curve. The baseline and interim PET/CT parameters, which respectively included maximum standardized uptake value (SUVmax0), total metabolic tumor volume (TMTV0), standardized total metabolic tumor volume (STMTV0), and the distance between the two furthest lesions (Dmax) and total tumor lesion glycolysis (TTLG1), SUVmax1, TMTV1, and the rate of change of SUVmax (%ΔSUVmax), and clinical characteristics were analyzed by chi-squared test, Kaplan-Meier survival curve, and Cox regression analysis. Results Of 154 patients, 35 exhibited disease progression or recurrence. ROC analysis revealed that baseline 18F-FDG PET/CT metabolic parameters, including maximum standardized uptake value (SUVmax0), total metabolic tumor volume (TMTV0), standardized total metabolic tumor volume (STMTV0), and the distance between the two furthest lesions (Dmax), along with interim 18F-FDG PET/CT metabolic parameters such as total tumor lesion glycolysis (TTLG1), SUVmax1, TMTV1, and the rate of change of SUVmax (%ΔSUVmax), were predictive of relapse or progression in DLBCL patients (P

Mantle cell lymphoma (MCL) is an intermediate-grade B-cell lymphoma, representing 2.8% of all non-Hodgkin lymphomas in the US. It is associated with t(11;14)(q13; q23), which leads to the overexpression of cyclin D1, consequently promoting cell proliferation. MCL usually expresses CD19, CD20, CD43, surface immunoglobulins, FMC7, BCL2, cyclin D1, CD5, and SOX11. Herein is a case of a 67-year-old male, referred to our facility with shortness of breath, anemia (hemoglobin of 5.3 g/dL), thrombocytopenia (12 × 109/L), and leukocytosis (283 × 109/L). A peripheral blood smear showed marked lymphocytosis with blastoid morphology. Morphologic examination of the bone marrow biopsy revealed a diffuse sheet of blastoid cells expressing CD20 and CD10, but without CD5 or cyclin D1. Given these features, a differential diagnosis of diffuse large B-cell lymphoma (DLBCL) with germinal center derivation, high-grade follicular lymphoma, and Burkitt lymphoma was considered, with the latter not favored due to morphology. Additional studies revealed positive SOX11, and fluorescence in situ hybridization (FISH) studies detected t(11;14). These additional studies supported diagnosis of the blastoid variant of MCL. In conclusion, we present a unique and challenging case of MCL without cyclin D1 or CD5, but with an expression of CD10 and SOX11, along with t(11;14). Pathologists should explicitly consider the blastoid variant of MCL when dealing with mature B-cell neoplasms with blastoid morphology in adults, and utilize a broad panel of ancillary studies, including FISH and SOX11.

Abstract Background Comprehensive molecular subtyping of diffuse large B‐cell lymphoma (DLBCL) through genetic profiling has broadened our understanding of DLBCL biology. In this study, we investigated whether DLBCL, not otherwise specified (NOS) shows differences in mutational patterns depending on the primary organ. Patients and Methods Panel‐based next‐generation sequencing was performed on 345 DLBCL from various primary organs, and patterns of mutations according to primary organs were analyzed. Results DLBCL showed a characteristic mutational signature in several primary organs. Among them, the mutational pattern of DLBCL in the breast and ileocecal area was particularly different from that of other DLBCL NOS. In breast DLBCL, MYD88L265P (57.1%), CD79B mutation (42.9%), and CDKN2A/B loss (71.4%) were found at high frequencies, which were similar to the mutation patterns of DLBCL of immune‐privileged sites compared with DLBCL NOS. DLBCL in the ileocecal area showed a characteristic mutation pattern with the most frequent TP53 mutation (52.6%) and 18q21 gain (42.1%). This was also different from the mutational pattern observed in the stomach or other intestines. In discriminant analysis, DLBCL of the breast and ileocecal area tended to form separate genetic constellations from other DLBCL NOS. Conclusion DLBCL NOS has a characteristic mutational profile that depends on the primary organ. In particular, the mutational signature of DLBCL in the breast and ileocecal area was heterogeneous compared with that of other DLBCL NOS. Further research is needed to determine whether primary DLBCL in the breast and ileocecal area can be classified as an independent subtype.

ObjectivesThis study aims to develop 7×7 machine-learning cross-combinatorial methods for selecting and classifying radiomic features used to construct Radiomics Score (RadScore) of predicting the mid-term efficacy and prognosis in high-risk patients with diffuse large B-cell lymphoma (DLBCL).MethodsRetrospectively, we recruited 177 high-risk DLBCL patients from two medical centers between October 2012 and September 2022 and randomly divided them into a training cohort (n=123) and a validation cohort (n=54). We finally extracted 110 radiomic features along with SUVmax, MTV, and TLG from the baseline PET. The 49 features selection-classification pairs were used to obtain the optimal LASSO-LASSO model with 11 key radiomic features for RadScore. Logistic regression was employed to identify independent RadScore, clinical and PET factors. These models were evaluated using receiver operating characteristic (ROC) curves and calibration curves. Decision curve analysis (DCA) was conducted to assess the predictive power of the models. The prognostic power of RadScore was assessed using cox regression (COX) and Kaplan–Meier plots (KM).Results177 patients (mean age, 63 ± 13 years,129 men) were evaluated. Multivariate analyses showed that gender (OR,2.760; 95%CI:1.196,6.368); p=0.017), B symptoms (OR,4.065; 95%CI:1.837,8.955; p=0.001), SUVmax (OR,2.619; 95%CI:1.107,6.194; p=0.028), and RadScore (OR,7.167; 95%CI:2.815,18.248; p

IntroductionFluorescence in situ hybridization (FISH) is an essential ancillary study used to identify clinically aggressive subsets of large B-cell lymphomas that have MYC, BCL2, or BCL6 rearrangements. Small-volume biopsies such as fine needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are increasingly used to diagnose lymphoma and obtain material for ancillary studies such as FISH. However, the performance of FISH in small biopsies has not been thoroughly evaluated or compared to surgical biopsies.MethodsWe describe the results of MYC, BCL2, and BCL6 FISH in a series of 222 biopsy specimens, including FNAB with cell blocks, CNBs, and surgical excisional or incisional biopsies from 208 unique patients aggregated from 6 academic medical centers. A subset of patients had FNAB followed by a surgical biopsy (either CNB or excisional biopsy) obtained from the same or contiguous anatomic site as part of the same clinical workup; FISH results were compared for these paired specimens.ResultsFISH had a low hybridization failure rate of around 1% across all specimen types. FISH identified concurrent MYC and BCL2 rearrangements in 20 of 197 (10%) specimens and concurrent MYC and BCL6 rearrangements in 3 of 182 (1.6%) specimens. The paired FNAB and surgical biopsy specimens did not show any discrepancies for MYC or BCL2 FISH; of the 17 patients with 34 paired cytology and surgical specimens, only 2 of the 49 FISH probes compared (4% of all comparisons) showed any discrepancy and both were at the BCL6 locus. One discrepancy was due to necrosis of the CNB specimen causing a false negative BCL6 FISH result when compared to the FNAB cell block that demonstrated a BCL6 rearrangement.DiscussionFISH showed a similar hybridization failure rate in all biopsy types. Ultimately, MYC, BCL2, or BCL6 FISH showed 96% concordance when compared across paired cytology and surgical specimens, suggesting FNAB with cell block is equivalent to other biopsy alternatives for evaluation of DLBCL or HGBCL FISH testing.

Exploring novel therapeutic targets of Diffuse large B cell lymphoma (DLBCL) to overcome its resistance to Bruton's Tyrosine Kinase (BTK) inhibitors is a key topic. Lipid metabolism, crucial in the resistance landscape of various cancers, may unlock new aspects of BTK inhibitor resistance in DLBCL. Despite the known importance of lipid metabolism in oncological resistance patterns, its intricate role in DLBCL and its resistance to BTK inhibitor therapies remains largely uncharted. This review will explore the complex relationship between lipid metabolism and BTK inhibitor resistance, giving new insights for improving the effectiveness of BTK inhibitors and developing innovative combination treatment methods for DLBCL. This review holds the potential for guiding future research directions, optimizing existing therapeutic processes, and inspiring the development of innovative combinatorial therapeutic strategies that improve outcomes in patients with DLBCL.

BackgroundReal-world health-related quality of life (HRQoL) data in patients with diffuse large B-cell lymphoma (DLBCL) are scarce. This study is to compare patient-reported outcomes in patients with DLBCL across therapy lines and countries.MethodsData were derived from the Adelphi DLBCL Disease Specific Programme™ from January 2021 to May 2021, a survey of physicians and their DLBCL patients in France, Germany, Italy, Spain, United Kingdom (UK), and the United States (US).ResultsOverall, analysis was conducted on 441 patients with DLBCL across Europe and the US (mean age 64.6 years, 64% male); 68% had an Ann Arbor stage III and 69% had an Eastern Cooperative Oncology Group Performance Status of 0 to 1. The mean overall GHS/QoL was 54.1; patients on their 3L+ therapy had a lower mean GHS/QoL compared with patients on 1L/2L (P = 0.0033). Further to this, mean EQ-5D-5L utility score was reduced from 0.73 for patients on 1L therapy to 0.66 for patients on 3L+ therapies (P = 0.0149). Mean percentages of impairment while working and overall work impairment were lower for patients receiving 3L+ therapy (12.5% and 17.7%; respectively) than those on 1L therapy (35.6% and 33.8%; respectively). When comparing region, patients in the US had significantly better scores for all functioning and symptomatic scales (per EORTC QLQ-C30) and work impairment (per WPAI) vs. patients with DLBCL in Europe. WPAI scores indicate that the overall activity impairment in the US was 36.6% and in Europe ranged from 42.4% in the UK to 54.9% in Germany. Mean EQ-5D-5L utility score for the US was 0.80, compared to 0.60 – 0.80 across the countries in Europe. Regression analysis showed patients who relapsed after more than one year of treatment were associated with better patient reported outcomes than those who relapse after less than one year.ConclusionPatient-reported outcomes of DLBCL patients remain poor and patients continue to experience considerable morbidity.

Diffuse large B-cell lymphoma (DLBCL) stands as the most prevalent subtype of non-Hodgkin's lymphoma and exhibits significant heterogeneity. Various forms of programmed cell death (PCD) have been established to have close associations with tumor onset and progression. To this end, this study has compiled 16 PCD-related genes. The investigation delved into genes linked with prognosis, constructing risk models through consecutive application of univariate Cox regression analysis and Lasso-Cox regression analysis. Furthermore, we employed RT-qPCR to validate the mRNA expression levels of certain diagnosis-related genes. Subsequently, the models underwent validation through KM survival curves and ROC curves, respectively. Additionally, nomogram models were formulated employing prognosis-related genes and risk scores. Lastly, disparities in immune cell infiltration abundance and the expression of immune checkpoint-associated genes between high- and low-risk groups, as classified by risk models, were explored. These findings contribute to a more comprehensive understanding of the role played by the 16 PCD-associated genes in DLBCL, shedding light on potential novel therapeutic strategies for the condition.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is a prevalent subtype of non-Hodgkin lymphoma (NHL) affecting predominantly elderly individuals. Case description: A 68-year-old man with a history of hypertension, hyperlipidaemia and a small pituitary gland tumour presented with sudden-onset binocular diplopia and right-eye blurry vision. A magnetic resonance imaging (MRI) of the brain revealed enhancing soft tissue in the right superolateral orbit inseparable from the lacrimal gland, extending medially to the right superior rectus muscle and soft tissue. Further scanning showed widespread metastasis to the bilateral retroperitoneal lymph nodes, adrenal gland, spine and lymph nodes in the neck. A biopsy of the lacrimal gland confirmed DLBCL. Conclusion: Primary lacrimal gland DLBCL is a rare and delayed diagnosis that often stems from the resemblance of its clinical manifestations to more benign conditions such as dacryocystitis, dacryostenosis or mucocele. Timely recognition and accurate diagnosis are essential for initiating appropriate treatment and improving patient outcomes.

Relapsed and refractory diffuse large B-cell lymphoma (DLBCL) is associated with poor prognosis. As such, a comprehensive analysis of intratumoral components, intratumoral heterogeneity, and the immune microenvironment is essential to elucidate the mechanisms driving the progression of DLBCL and to develop new therapeutics. Here, we used single-cell transcriptome sequencing and conventional bulk next-generation sequencing (NGS) to understand the composite tumor landscape of a single patient who had experienced multiple tumor recurrences following several chemotherapy treatments. NGS revealed several key somatic mutations that are known to contribute to drug resistance. Based on gene expression profiles at the single-cell level, we identified four clusters of malignant B cells with distinct transcriptional signatures, showing high intra-tumoral heterogeneity. Among them, heterogeneity was reflected in activating several key pathways, human leukocyte antigen (HLA)-related molecules’ expression, and key oncogenes, which may lead to multi-drug resistance. In addition, FOXP3+ regulatory CD4+ T cells and exhausted cytotoxic CD8+ T cells were identified, accounted for a significant proportion, and showed highly immunosuppressive properties. Finally, cell communication analysis indicated complex interactions between malignant B cells and T cells. In conclusion, this case report demonstrates the value of single-cell RNA sequencing for visualizing the tumor microenvironment and identifying potential therapeutic targets in a patient with treatment-refractory DLBCL. The combination of NGS and single-cell RNA sequencing may facilitate clinical decision-making and drug selection in challenging DLBCL cases. [ABSTRACT FROM AUTHOR]

Aim: To assess treatment patterns, healthcare resource utilization (HCRU), and costs for patients with diffuse large B-cell lymphoma (DLBCL) who did not receive stem cell transplantation in second-line. Patients & methods: An administrative MarketScan® database study to assess DLBCL claims from 01/01/2009–30/09/2020. Results: Most patients (n = 750) received rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone in first-line (86.8%) and rituximab (39.5%) or bendamustine ± rituximab ± other (16.3%) in second-line. Over half were hospitalized (mean duration: 16.5 (standard deviation [SD]: 25.8) days per patient per year). Mean medical/pharmacy costs were US$141,532 per patient per year (SD: $189,579), driven by DLBCL-related claims. Conclusion: Healthcare resource utilization and costs for DLBCL-related claims were due to hospitalizations and outpatient visits. Novel therapies to reduce clinical and economic burdens are needed. In a study of patients with diffuse large B-cell lymphoma who do not proceed to transplant in second line, high HCRU and costs were mostly due to hospitalizations and outpatient visits. [ABSTRACT FROM AUTHOR]

In this hypothesis-generating analysis, we examined whether longitudinal changes in patient-reported outcomes (PROs), such as symptoms, over time would be prognostic for progression-free survival (PFS) and overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL) who were newly treated with obinutuzumab (G) in combination with CHOP (G-CHOP) or rituximab (R) with CHOP (R-CHOP), in the GOYA Phase 3 trial (NCT01287741). Our results show that from the study baseline to cycle 3 day 1, every 1-point increase (worsening) in fever symptoms was associated with a 41% higher risk of death (hazard ratio [HR], 1.41; P = 0.01). Every 1-point increase (worsening) in lumps or swelling symptoms was associated with a 27% higher risk of disease progression or death (PFS events) (HR, 1.27; P = 0.01) and a 29% higher risk of death (OS events) (HR, 1.29; P = 0.02). No significant associations were observed between survival and changes in other symptoms, such as itching. Our study suggests that changes in some PROs are related to survival in DLBCL patients. [ABSTRACT FROM AUTHOR]

Introduction: Chimeric antigen receptor (CAR) T cell therapy has markedly improved the prognosis of patients with diffuse large B‐cell lymphoma (DLBCL). The relative positioning of tumor lesions in lymphoma varies among patients, manifesting as either aggregation (clumped together) or dissemination (spread throughout the body). Prognostic significance of factors indicating the relative positioning of tumor lesions in CAR T cell therapy remains underexplored. For aggregation, prior research proposed the tumor volume surface ratio (TVSR), linking it to prognosis in chemotherapy. Regarding dissemination, indicators such as disease stage or extranodal involvement, commonly used in clinical practice, have not demonstrated prognostic significance in CAR T cell therapy. This study aims to analyze current indicators of tumor aggregation or dissemination and introduce a novel indicator to assess the prognostic value of tumor lesions' relative positioning in DLBCL patients undergoing CAR T cell therapy. Methods: This retrospective study included 42 patients receiving CAR T cell therapy. Lesion image information was obtained from the last PET/CT scan prior to CAR T cell infusion, including total metabolic tumor volume, total tumor surface, diameter of lymphoma masses, and the sites of tumor lesions. We evaluated TVSR and bulky disease as descriptors of tumor aggregation. We refined existing indicators, stage III&IV and >1 site extranodal involvement, to distill a new indicator, termed 'extra stage', to better represent tumor dissemination. The study examined the prognostic significance of tumor aggregation and dissemination. Results: Our findings indicate that TVSR, while prognostically valuable in chemotherapy, lacks practical prognostic value in CAR T cell therapy. Conversely, bulky disease emerged as an optimal prognostic indicator of tumor aggregation. Both bulky disease and extra stage were associated with poor prognosis and exhibiting synergistic prognostic impact in CAR T cell therapy. Conclusions: Overall, the relative positioning of tumor lesions significantly influences the prognosis of patients with DLBCL receiving CAR T cell therapy. The ideal scenario involves tumors with minimal dissemination and no aggregation. The relative positioning of tumor lesions is associated with the prognosis of patients with DLBCL receiving CAR T cell therapy.The tumor lesion with limited dissemination and no aggregation is the most ideal. [ABSTRACT FROM AUTHOR]

To provide insights into targetable oncogenic pathways, this retrospective cohort study investigated the genetic profile of 26 patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), and two patients with high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL) presenting in the ocular adnexa. Pathogenic variants and copy number variations in 128 B-cell lymphoma-relevant genes were analyzed by targeted next-generation sequencing. Genetic subtypes were determined with the LymphGen algorithm. Primary ocular adnexal DLBCL-NOS constituted 50% (n = 14) and was generally characterized by non-germinal center B-cell origin (non-GCB) (n = 8, 57%), and LymphGen MCD subtype (n = 5, 36%). Primary ocular adnexal DLBCL-NOS presented pathogenic variants in genes involved in NF-κB activation and genes which are recurrently mutated in other extranodal lymphomas of non-GCB origin, including MYD88 (n = 4, 29%), CD79B (n = 3, 21%), PIM1 (n = 3, 21%), and TBL1XR1 (n = 3, 21%). Relapsed DLBCL-NOS presenting in the ocular adnexa (n = 6) were all of non-GCB origin and frequently of MCD subtype (n = 3, 50%), presenting with a similar genetic profile as primary ocular adnexal DLBCL-NOS. These results provide valuable insights into genetic drivers in ocular adnexal DLBCL-NOS, offering potential applications in future precision medicine. [ABSTRACT FROM AUTHOR]

Some patients with marginal zone lymphoma (MZL) experience histological transformation to diffuse large B‐cell lymphoma (DLBCL). Because of the paucity of long‐term data on transformation, we conducted a population‐based study to estimate the risk of transformation and its impact on survival in MZL. Using the Surveillance, Epidemiology and End Results database, we identified 23 221 patients with histology‐proven MZL between 2000 and 2018. Competing risk method, Kaplan‐Meier and Cox proportional hazards regression were performed to analyze time‐to‐event outcomes. Based on 420 events of transformation, the 10‐year cumulative incidence rate of transformation is 2.23% (95% CI: 2.00%‐2.46%) in MZL, 1.5% (95% CI: 1.3%‐1.8%), 2.7% (95% CI: 2.3%‐3.2%) and 5.8% (95% CI: 4.6%‐7.1%) in extranodal, nodal and splenic MZL (EMZL, NMZL and SMZL), respectively. Patients with SMZL (subdistribution hazard ratio [SHR], 2.96; 95% CI: 2.21‐3.96) or NMZL (SHR, 1.49; 95% CI: 1.17‐1.90) have a higher risk of transformation than those with EMZL. For each MZL subtype, patients with transformation had a significantly shorter overall survival. Patients with transformation >18 months since MZL diagnosis had longer OS than those who presented within 18 months (5‐year rate, 87.4% [95% CI: 83.7%‐91.2%] vs 47.9% [95% CI: 38.8%‐59.0%]; P <.001). Compared to patients with matched de novo DLBCL, those whose DLBCL was transformed from MZL had a shorter OS (5‐year rate, 56.6% [95% CI: 51.9%‐61.8%] vs 46.1% [95% CI: 40.9%‐51.9%]; P <.001). We concluded that patients with SMZL had the highest risk of transformation. Regardless of MZL subtype, transformation resulted in significantly increased mortality. [ABSTRACT FROM AUTHOR]

The present study aimed to elucidate the prognostic mutation signature (PMS) associated with long-term survival in a diffuse large B-cell lymphoma (DLBCL) cohort. All data including derivation and validation cohorts were retrospectively retrieved from The Cancer Genome Atlas (TCGA) database and whole-exome sequencing (WES) data. The Lasso Cox regression analysis was used to construct the PMS based on WES data, and the PMS was determined using the area under the receiver operating curve (AUC). The predictive performance of eligible PMS was analyzed by time-dependent receiver operating curve (ROC) analyses. After the initial evaluation, a PMS composed of 94 PFS-related genes was constructed. Notably, this constructed PMS accurately predicted the 12-, 36-, and 60-month PFS, with AUC values of 0.982, 0.983, and 0.987, respectively. A higher level of PMS was closely linked to a significantly worse PFS, regardless of the molecular subtype. Further evaluation by forest plot revealed incorporation of international prognostic index or tumor mutational burden into PMS increased the prediction capability for PFS. The drug-gene interaction and pathway exploration revealed the PFS-related genes were associated with DNA damage, TP53, apoptosis, and immune cell functions. In conclusion, this study utilizing a high throughput genetic approach demonstrated that the PMS could serve as a prognostic predictor in DLBCL patients. Furthermore, the identification of the key signaling pathways for disease progression also provides information for further investigation to gain more insight into novel drug-resistant mechanisms. [ABSTRACT FROM AUTHOR]

Background: Papillary carcinoma is the most frequent type of thyroid carcinoma, while primary thyroid lymphoma is uncommon disease. The coexistence of these entities has already been described, and the common risk factor is considered Hashimoto thyroiditis. The two most frequent histotypes of primary thyroid lymphoma are diffuse large B-cell and mucosa-associated lymphoid tissue lymphoma, but the coexistence of both with papillary carcinoma is rarely reported. Methods: We present a case of a previously healthy 57-years old male with rapidly growing lump on the right side of the neck. Ultrasonography revealed nodules in both thyroid lobes. Fine needle aspiration cytology and pertechnetate scintigraphy were performed. Due to the Bethesda T-5 in the "cold" nodule of the right lobe, surgery with histopathological and immunohistochemistry analysis was indicated. Results: Histopathological and immunohistochemistry methods confirmed concomitant malignancies in the thyroid gland: diffuse large B-cell lymphoma and papillary carcinoma in the right, and mucosa-associated lymphoid tissue lymphoma in the left lobe with Hashimoto thyroiditis in the remaining tissue. Patient underwent therapy procedures and was without signs of local recurrence or metastatic spread on subsequent follow-up. Conclusions: Sudden appearance of the neck mass in patients with Hashimoto thyroiditis should raise suspicion on primary thyroid lymphoma and be promptly taken in the diagnostic workup, including fine needle aspiration cytology. Pathology with immunohistochemistry is crucial for further clinical decision making. Since the standardized protocol in management of these complex patients is missing, personal approach and close collaboration between cytologist, pathologist, surgeon, haematologist and nuclear medicine specialist is essential. [ABSTRACT FROM AUTHOR]

AIM: To investigate the role of Ywhab in the growth of mouse B-cell lymphoma, and to explore the potential underlying mechanisms. METHODS : The correlation between Ywhab and human diffuse large B-cell lymphoma (DLBCL) was investigated by bioinformatics analysis. Infection with retroviral vector was performed to establish stable mouse B-cell lymphoma 38B9 cell line with overexpression of Ywhab gene, which was verified by RT-qPCR and Western blot. The impact of Ywhab overexpression on 38B9 cell growth both in vitro and in vivo was detected by cell counting, CCK-8 assay, and subcutaneous tumor loading experiments. The expression of apoptosis-related proteins was detected by RT-qPCR and Western blot. Co-immunoprecipitation combined with mass spectrometry (CoIP-MS) was employed to search for proteins specifically binding to Ywhab gene product 14-3-3β, which was confirmed by Western blot and molecular docking analysis. RESULTS: The Ywhab gene exhibited low expression in DLBCL, which was correlated with poor clinical prognosis of DLBCL patients. Compared with normal mouse bone marrow B cells, Ywhab expression was low in 38B9 cells. Overexpression of Ywhab induced apoptosis of 38B9 cells both in vitro and in vivo, promoted the expression of pro-apoptotic proteins Puma, Noxa and Bax at both mRNA and protein levels, and inhibited the mRNA and protein expression of anti-apoptotic protein Bcl2 (P<0. 05). The 14-3-3β protein specifically bound to Hsp90aa1 and reduced Hsp90aa1 protein levels, thereby suppressing the growth of 38B9 cells. CONCLUSION: Ywhab promotes the apoptosis of B-cell lymphoma cells by binding to Hsp90aa1 and thereby inhibiting the function of Hsp90aa1. [ABSTRACT FROM AUTHOR]

Predicting prognosis is crucial in older patients with diffuse large B-cell lymphoma (DLBCL). This study evaluated the prognostic impact of the controlling nutritional status (CONUT) score, a simple nutritional index, for older DLBCL patients (≥65 years of age) treated with R-CHOP-like regimens in a retrospective, cohort study including 203 patients. The CONUT score was an independent prognostic factor for overall survival (hazard ratio 1.11, 95% confidence interval (CI) 1.01-1.21, p = 0.032) in a multivariable Cox proportional hazards model. On receiver-operating characteristic analysis, the optimal cutoff value was 3. The CONUT score (≥3 or <3) effectively stratified older DLBCL patients, regardless of the International Prognostic Index (p = 0.71 for interaction). Further, the CONUT score independently affected initial dose intensity (odds ratio 0.84, 95% CI 0.73-0.95, p = 0.008), likely reflecting the patients' status at diagnosis and affecting dose adjustments. In conclusion, the CONUT score is associated with a poorer prognosis in older DLBCL patients. [ABSTRACT FROM AUTHOR]

Objective: Anemia is common in cancer patients and has adverse effects on prognosis. In this study, we investigated the prevalence, etiological causes, and effects of anemia on the prognosis of patients with lymphoma. Methods: We analyzed 153 newly diagnosed lymphoma cases. The hemoglobin (Hb) cut-off value for the diagnosis of anemia was set as Hb <12 g/dL in women and Hb <13 g/dL in men. Cases with anemia were classified as mild (Hb =10 g/dL-normal value), moderate (Hb =8-9.9 g/dL), and severe (Hb <8 g/dL) anemia. The relationship between the presence and degree of anemia and the revised international prognostic index (r-IPI) score, Eastern Cooperative Oncology Group performance score, Ann Arbor stage, presence of B symptoms, bulky mass, extra-nodal involvement, and life status was evaluated. Results: Anemia was detected in 82 (53.6%) patients, and the most common cause of anemia was chronic disease anemia (30.5%). There was no significant relationship between the presence of anemia and the presence of bulky mass, r-IPI score, performance score, or Ann Arbor stage. A significant correlation was found between the degree of anemia and the presence of extranodal involvement and B symptoms (p<0.001, p=0.01, respectively). A significant correlation was found between the presence and degree of anemia and overall survival (p=0.011, p<0.001, respectively). Conclusion: Anemia is common in Hodgkin and diffuse large B-cell lymphoma patients and is associated with some worse prognostic factors. Therefore, further studies examining more cases and including patients in all non-Hodgkin lymphoma subgroups are needed to better understand the importance of anemia in lymphoma cases. [ABSTRACT FROM AUTHOR]