Mantle cell lymphoma (MCL) is a rare, incurable, and aggressive B-cell non-Hodgkin lymphoma (NHL). Early MCL diagnosis and treatment is critical and puzzling due to inter/intra-tumoral heterogeneity and limited understanding of the underlying molecular mechanisms. We developed and applied a multifaceted analysis of selected publicly available transcriptomic data of well-defined MCL stages, integrating network-based methods for pathway enrichment analysis, co-expression module alignment, drug repurposing, and prediction of effective drug combinations. We demonstrate the \"butterfly effect\" emerging from a small set of initially differentially expressed genes, rapidly expanding into numerous deregulated cellular processes, signaling pathways, and core machineries as MCL becomes aggressive. We explore pathogenicity-related signaling circuits by detecting common co-expression modules in MCL stages, pointing out, among others, the role of VEGFA and SPARC proteins in MCL progression and recommend further study of precise drug combinations. Our findings highlight the benefit that can be leveraged by such an approach for better understanding pathobiology and identifying high-priority novel diagnostic and prognostic biomarkers, drug targets, and efficacious combination therapies against MCL that should be further validated for their clinical impact.

BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) are a group of malignant neoplasms with extensive clinical and molecular heterogeneity. Several key genetic aberrations have been identified, such as those involving the MYC, BCL6, and BCL2 genes. Prior studies on the prognostic significance of Bcl-2 protein expression in DLBCL have been contradictory, with some suggesting it has an adverse effect, while others have shown no such association. Bcl-2 is known to be more highly expressed in the non-germinal center B-cell-like (non-GCB) subtype compared to germinal center B-cell-like (GCB) DLBCL. Non-GCB status is associated with a less favorable prognosis. This study aimed to investigate whether the expression of Bcl-2 protein in non-GCB DLBCL influences response to treatment, progression-free survival, or overall survival.
METHODS: In this retrospective study, we investigated whether there was a difference in the clinical outcomes of non-GCB DLBCL cases (n = 97) that were confirmed by immunochemistry to demonstrate high levels of Bcl-2 protein expression (>50% neoplastic cells stained) when compared to those who were deemed negative based on this criterion. Response to rituximab-based induction immunochemotherapy, five-year progression-free survival, and five-year overall survival were assessed.
RESULTS: There was no statistically significant difference in response to treatment, five-year progression-free survival, or five-year overall survival between the patients who were positive for Bcl-2 (n = 70) compared to those who were considered Bcl-2 negative (n = 27).
CONCLUSIONS: High levels of Bcl-2 protein expression do not appear to be of prognostic significance in non-GCB DLBCL and therefore Bcl-2 may not be a key therapeutic target in the treatment and improvement of clinical outcome in such cases.

The Food and Drug Administration and the European Medicines Agency have recently approved chimeric antigen receptor-engineered (CAR) T cells to treat several refractory/relapsed B-cell lymphomas. This comprehensive review aims to demonstrate the pivotal role that [18F]-FDG PET/computed tomographic (CT) imaging can play to enhance the care of patients treated with CAR T-cell therapy. To this end, this review deciphers evidence showing the diagnostic, prognostic, predictive, and theragnostic value of [18F]-FDG PET/CT-derived parameters.

Fluorine-18-deoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) has been shown to be superior to other conventional imaging modalities in the detection of extra-nodal lymphomatous localizations. Especially in neurolymphomatosis which is rarely encountered in high-grade lymphomas. We report a case of a woman diagnosed with non-Hodgkin lymphoma, whose initial staging with [18F]FDG PET/CT showed increased [18F]FDG uptake along the brachial and sacral plexuses. [18F]FDG PET/CT remains the most appropriate diagnostic tool in these cases, whose prognosis is often poor.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare type of non-Hodgkin lymphoma (NHL). We present a case of a 60-year-old female who attended the emergency department (ED) with fatigue, recurrent fever, weight loss, and adenopathy for six months. Laboratory findings showed anemia, lymphocytosis, eosinophilia, thrombocytosis, cholestasis, hypoproteinemia, and hypoalbuminemia. Abdominopelvic computed tomography (CT) revealed multiple adenopathies. A lymph node biopsy yielded inconclusive results in the outpatient clinic. Later, during admission, the patient underwent a positron emission tomography-computed tomography (PET-CT), revealing a cervical adenopathy cluster that was excised en bloc. Histology confirmed the diagnosis of AITL. The medical team initiated chemotherapy but opted for exclusive symptomatic treatment due to disease progression. The patient died six months after diagnosis. The fluctuating and nonspecific presentation of AITL can hinder and delay definitive diagnosis, therefore impacting treatment and prognosis.

BACKGROUND: Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma associated with Plasmodium falciparum and Epstein-Barr virus, both of which affect metabolic pathways. The metabolomic patterns of BL is unknown.
METHODS: We measured 627 metabolites in pre-chemotherapy treatment plasma samples from 25 male children (6-11 years) with BL and 25 cancer-free area- and age-frequency-matched male controls from the Epidemiology of Burkitt Lymphoma in East African Children and Minors study in Uganda using liquid chromatography-tandem mass spectrometry. Unconditional, age-adjusted logistic regression analysis was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for the BL association with 1-standard deviation increase in the log-metabolite concentration, adjusting for multiple comparisons using false discovery rate (FDR) thresholds and Bonferroni correction.
RESULTS: Compared to controls, levels for 42 metabolite concentrations differed in BL cases (FDR < 0.001), including triacylglyceride (18:0_38:6), alpha-aminobutyric acid (AABA), ceramide (d18:1/20:0), phosphatidylcholine ae C40:6 and phosphatidylcholine C38:6 as the top signals associated with BL (ORs = 6.9 to 14.7, P < 2.4✕10- 4). Two metabolites (triacylglyceride (18:0_38:6) and AABA) selected using stepwise logistic regression discriminated BL cases from controls with an area under the curve of 0.97 (95% CI: 0.94, 1.00).
CONCLUSIONS: Our findings warrant further examination of plasma metabolites as potential biomarkers for BL risk/diagnosis.

UNASSIGNED: Despite advances in the treatment of oncology patients, therapy-related side effects may lead to premature morbidity. Inflammatory activation that has been linked to cardiovascular disease is crucial for the pathogenesis of both Hodgkin (HL) and non-Hodgkin lymphoma (NHL).
UNASSIGNED: The purpose of this study was to assess the vascular effects of chemotherapy in patients with HL and NHL by positron emission tomography/computed tomography with 18-fluorodeoxyglucose (18-FDG PET/CT) and to investigate interactions with systemic inflammation as assessed by circulating inflammatory markers.
UNASSIGNED: Between July 2015 and July 2019, 65 consecutive patients (mean age 56 ± 17.78 years) with confirmed diagnosis of either HL (n = 33) or NHL (n = 32) were prospectively studied. PET/CT imaging was performed at baseline, at an interim phase, and after first-line treatment. Aortic FDG uptake was assessed by measuring global aortic target-to-background ratio (GLA-TBR). Serum biomarkers interleukin (IL)-6 and IL-1b were measured at each phase.
UNASSIGNED: Patients with HL demonstrated significant reduction in aortic TBR after first-line treatment (median GLA-TBR baseline: 1.98, median GLA-TBR third scan: 1.75, median difference = -0.20, 95% CI: -0.07 to -0.33, P = 0.006), which remained significant after adjustment for confounders (adj. R2 of model = 0.53). In contrast, patients with NHL did not demonstrate a significant aortic inflammation response (P = 0.306). Furthermore, patients with HL demonstrated a significant reduction in IL-6 (P = 0.048) and IL-1b (P = 0.045), whereas patients with NHL did not demonstrate significant reduction in IL-6 (P = 0.085) and IL-1b levels (P = 0.476).
UNASSIGNED: Aortic inflammation, as assessed by 18-FDG PET/CT, is reduced in HL patients after first-line treatment but not in NHL patients. These findings imply that different pathophysiological pathways and different therapies might affect the arterial bed in different ways for patients with lymphoma.

Splenic rupture and hematoma are significant complications that can occur in patients with non-Hodgkin lymphoma (NHL). Understanding these associated complications is essential for optimal patient management and enhanced patient outcomes. Histopathological and immunohistochemical analyses are crucial in diagnosing NHL and assessing splenic involvement. In this study, a judicial autopsy had been requested by the Prosecutor\'s Office for a malpractice claim due to a fall in the hospital. In the Emergency Department, a 72-year-old man fell from a gurney and reported sustaining a wound to his forehead. No other symptoms were reported. A face and brain CT scan showed no abnormalities. Nine days after discharge, the patient presented with abdominal pain. An abdominal CT revealed splenic rupture and hemoperitoneum. The patient underwent open splenectomy but showed signs of hemodynamic shock and subsequently died. The evidence from the autopsy allowed us to diagnose mantle cell non-Hodgkin lymphoma with spleen involvement, previously unknown. Histopathological and immunohistochemical analyses were performed to assess the diagnosis of splenic rupture and estimate its timing. The findings strongly suggest that the splenic rupture was associated with the patient\'s fall and the pre-existing malignancy. This case highlights the importance of considering an underlying hematological malignancy when investigating delayed splenic rupture. An immunohistochemical study of spleen samples allowed the timing of splenic hematoma and rupture to be assessed, leading to the establishment of a causal relationship with trauma.

Systemic capillary leak syndrome (SCLS) is a rare entity that is frequently idiopathic or, rarely, associated with infections, autoimmune diseases, drugs, surgery, and cancer. Several cancers can directly cause SCLS, although it is very uncommon as the inaugural presentation of a non-Hodgkin lymphoma. We report a case of SCLS as a paraneoplastic syndrome which revealed a large B-cell lymphoma, a non-Hodgkin lymphoma of B-cell origin.

We observed lack of clarity and consistency in end point definitions of large randomized clinical trials in diffuse large B-cell lymphoma. These inconsistencies are such that trials might, in fact, address different clinical questions. They complicate interpretation of results, including comparisons across studies. Problems arise from different ways to account for events occurring after randomization including absence of improvement in disease status, treatment discontinuation or the initiation of new therapy. We call for more dialogue between stakeholders to define with clarity the questions of interest and corresponding end points. We illustrate that assessing different end point rules across a range of plausible patient journeys can be a powerful tool to facilitate such a discussion and contribute to better understanding of patient-relevant end points.
What is this article about? This article talks about the lack of clarity and consistency in the definitions of outcomes used in clinical trials that investigate new treatments for diffuse large B-cell lymphoma. This is mainly due to how these different outcome definitions handle events such as absence of improvement in disease status, treatment discontinuation or initiation of new treatment. The authors discuss how these inconsistencies make it hard to interpret the results of individual clinical trials and to compare results across clinical trials.Why is it important? Defining the above events and consequently defining outcomes affects what we can learn from the trials and can lead to different results. Some approaches may not reflect good and bad outcomes for patients appropriately. This makes it challenging for patients, physicians, health authorities and payors to understand the true benefit of treatments under investigation and which one is better.What are the key take-aways? This article serves as a call-to-action for more dialogue among all stakeholders involved in drug development and the decision-making process related to drug evaluations. There is an urgent need for clinical trials to be designed with more clarity and consistency on what is being measured so that relevant questions for patients and prescribing physicians are addressed. Understanding patient journeys will be key to successfully understand what truly matters to patients and how to measure the benefit of new treatments. Such discussions will contribute toward more clarity and consistency in the evaluation of new treatments.