Search Results (5,306)

Among hematological malignancies, lymphoma is associated with an increased incidence of venous thromboembolism (VTE) ranging between 4 and 12%. Although Khorana score was validated for stratifying VTE risk in cancer, its discrimination reliability in lymphoma is reduced by the lack of specific predictors. The aim of this systematic review was to summarize the evidence regarding predictors and available risk assessment models (RAMs) for VTE in patients with lymphoma. A systematic search was conducted on PubMed, Embase and Scopus in order to identify papers published until February 2026, which evaluated predictors and RAMs for VTE in patients diagnosed with lymphoma. Out of 592 evaluated papers, 44 met the inclusion criteria. The widely used Khorana score failed to appropriately identify patients with lymphoma at high risk for VTE, while the Thrombosis Lymphoma predictive score (ThroLy) showed modest improvement. Strong predictors for VTE were a poor performance status, older age, previous history of VTE, the use of central venous catheters, and bulky disease. However, the lack of external validation, the small sample size and bias due to confounding factors limit the generalizability of the results. Therefore, larger studies with external validation cohorts are needed to design lymphoma-specific RAMs and to identify predictors with high discrimination power. Full article

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma endemic in children in regions of sub-Saharan Africa, where its incidence geographically overlaps holoendemic Plasmodium falciparum malaria and poorly controlled childhood Epstein–Barr virus (EBV) infection. Despite decades of research, the precise mechanistic synergy between these two pathogens remains incompletely defined. This review synthesizes current epidemiological, immunological, and molecular evidence to propose an integrated model for the etiology of endemic BL. We outline a paradoxical, dual-edged relationship wherein EBV infection during infancy may provide a short-term child survival advantage against severe malaria while simultaneously increasing the long-term oncogenic risk in B-cells infected by EBV. P. falciparum infection triggers polyclonal B-cell activation, increasing the probability of an activation-induced cytidine deaminase (AID)-mediated c-MYC translocation in proportion to the recurrent parasite burden. Concurrently, EBV expands within this B-cell pool and modulates the host immune response, potentially through viral interleukin-10 (vIL-10), to prevent lethal malarial inflammation. At the cellular level, EBV provides a critical “second hit” when it establishes latency I infection that rescues c-MYC-translocated B-cells from apoptosis. This framework explains why BL manifests as a “tumor of malaria survivors,” peaking in incidence years after the highest-risk period for malaria mortality. Ultimately, this model underscores that malaria control is a critical form of cancer control and highlights key future directions for validating these pathways in prospective clinical studies. Full article

Non-Hodgkin lymphomas (NHL) are lymphoproliferative neoplasms with a heterogenous genetic landscape that require multiple assays to be characterized. Cytological samples are frequently utilized in the diagnosis of NHL. An RNA-based assay was utilized to detect translocations and identify mutations in fine-needle aspiration cytology (FNAC) samples of NHL. Fragmentation index and RNA concentration were evaluated in 54 FNAC and eight corresponding histological samples of NHL to establish first the material adequacy before sequencing. To sequence FusionPlex Lymphoma (ArcherDX, Boulder, USA), an anchored multiplex polymerase chain reaction-based RNA targeting 125 genes was used. The sequencing data processing was entirely carried out on the ArcherDX online platform. Mutations were detected in 21 of 62 samples (34%), and in 41 of 62 samples (66%), no genomic alterations were found. The FusionPlex assay detected five BCL6 translocations (three IGH-BCL6 and two EIF4A2-BCL6), six IGH-BCL2 translocations, two IGH-CCND1 translocations, two TP53 point mutations, two MYD88 mutation and four uncommon translocations (two EIF4E3-FOXP1, one TBL1XR1-TP63, one LOC105370537-FUT8). In eight out of eight cases, there was NGS (Next Generation Sequencing) results concordance between corresponding cytological and histological samples (100% concordance). FNAC samples of NHL are suitable for molecular assessment by NGS and FusionPlex Lymphoma assay is an effective method for this purpose. NGS allows the detection of mutations and the identification of translocations on cytological samples also with scanty diagnostic material. Full article

Introduction: Cutaneous T cell lymphoma (CTCL), most commonly known as mycosis fungoides (MF), is characterized by an increasingly immunosuppressive tumor microenvironment (TME) as the disease progresses. Cancer-associated fibroblasts (CAFs) are key stromal components that support a permissive niche, in part through the secretion of small extracellular vesicles (sEVs), predominantly exosomes, that mediate intercellular communication. We investigated the immunomodulatory role of exosome-enriched sEVs derived from MF fibroblasts (MF-Fs) compared to normal fibroblasts (N-Fs). Materials and Methods: Primary MF-Fs from early-stage MF biopsies and N-Fs from healthy skin were cultured in vitro. sEVs enriched with exosomes were isolated by ultracentrifugation and characterized by flow cytometry (CD81), electron microscopy, Nanosight analysis, and protein quantification, and their uptake by normal peripheral blood mononuclear cells (nPBMCs) was confirmed using PKH26-labeled sEVs. nPBMCs, monocytes, CD4⁺ and CD8⁺ T cells from healthy donors were exposed to MF-F or N-F sEVs. Cell viability was assessed using MTT and trypan blue exclusion assays. Mass cytometry (CyTOF) profiled immune subsets and regulatory proteins for preliminary observation. Monocyte polarization was evaluated by flow cytometry for M1 (CD80, CD86) and M2 (CD163, CD206) markers and PD-L1 expression; M1/M2-associated cytokines and sEV-microRNAs were quantified by qRT-PCR. Results: Both MF-F and N-F sEVs were internalized by nPBMCs and reduced their viability, with a more pronounced effect observed for MF-F sEVs. In nPBMCs, MF-F sEVs also increased the frequency of M2-like macrophages, decreased M1 polarization, and enhanced PD-L1 expression. In primary monocytes, MF-F- compared with N-F-derived sEVs upregulated M2-associated cytokines (IL-10, TGF-β), increased PD-L1 expression, and generated M2-like cells that suppressed CD4⁺ and CD8⁺ T cell viability. Conclusions: MF-F sEVs promote an immunosuppressive TME and represent potential therapeutic or biomarker targets in MF. Full article

Background/Objectives: Kimura disease is a rare, chronic immune-mediated disorder that classically produces painless head-and-neck masses, regional lymphadenopathy, blood eosinophilia, and a raised serum immunoglobulin E (IgE). Almost all reported patients are young East Asian men, and the condition is seldom encountered in the Middle East, where it is easily mistaken for lymphoma or another eosinophilic disorder. We describe a histologically confirmed case in a Saudi adolescent and review the literature to compare treatment strategies and outcomes across populations. Methods: We documented the clinical course, laboratory profile, histopathological findings, and 15-month outcome of the patient, and searched PubMed for reported cases of Kimura disease, with emphasis on pediatric and non-Asian series. Results: A 16-year-old boy presented with a one-year history of painless right cervical swelling, constitutional symptoms and striking eosinophilia (36%; absolute eosinophil count 6.5 × 10⁹/L). Hematological malignancy was excluded through bone-marrow examination, flow cytometry and molecular studies. Excisional lymph node biopsy revealed the diagnostic triad—reactive follicular hyperplasia, a dense eosinophilic infiltrate with microabscesses, and vascular proliferation—together with IgE-positive immunostaining. Complete remission followed surgical excision alone and was maintained at 15 months without systemic corticosteroids. Conclusions: Kimura disease occurs well beyond its traditional geographic boundaries and belongs in the differential diagnosis of eosinophilia accompanied by lymphadenopathy. Although corticosteroids remain the mainstay for extensive disease, relapse on tapering is common, whereas complete excision can secure lasting remission in localized pediatric disease while sparing patients from steroid-related toxicity. Full article

Background/Objectives: Although outcomes in Hodgkin lymphoma (HL) have improved substantially, patients with advanced-stage disease, comorbidities, or relapsed/refractory presentations can still fare poorly. Blood-based indices of systemic inflammation and nutrition are derived from routine tests, but their value beyond established prognostic models is uncertain. We examined the association of the baseline Gustave Roussy Immune Score (GRIm) and Glasgow Prognostic Score (GPS) with treatment response, progression-free survival (PFS), and overall survival (OS) in HL, focusing on their performance relative to the seven-factor International Prognostic Score (IPS-7). Methods: We retrospectively analysed 110 adults with histologically confirmed HL treated at a tertiary haematology centre between January 2015 and December 2025. GPS, GRIm, and IPS-7 were calculated from data recorded at diagnosis. Treatment response was classified as complete versus non-complete. Outcomes were assessed with Kaplan–Meier analysis, log-rank tests, Cox regression, Harrell’s C-index, and likelihood-ratio testing. Results: Most patients had advanced-stage disease (69.1%) and received ABVD-based treatment (94.5%); complete response was achieved in 90 (81.8%). GPS and GRIm were not significantly associated with non-complete response, whereas IPS-7 was. Over a median follow-up of 39.5 months, 28 patients (25.5%) progressed or died and 17 (15.5%) died. In univariable Cox analysis, high GRIm risk (HR = 2.68, 95% CI 1.17–6.14), higher GPS (HR = 2.18 per point, 95% CI 1.23–3.89), and higher IPS-7 (HR = 2.10 per point, 95% CI 1.59–2.77) predicted shorter PFS. For OS, GPS and IPS-7 were significant, whereas GRIm was not. After adjustment for IPS-7, neither GPS nor GRIm remained independently associated with PFS or OS, and adding either score to IPS-7 produced only small, non-significant gains in discrimination. Conclusions: Baseline GPS and GRIm were associated with survival on univariable analysis, particularly for PFS, but their incremental value beyond IPS-7 was limited. These scores may help describe baseline inflammatory and nutritional risk and should not be regarded as alternatives to established HL prognostic models. In particular, GPS and GRIm were not significantly associated with treatment response and should be viewed as supportive markers requiring external validation, rather than as tools that can independently guide treatment decisions. Full article

Background/Objectives: Patients with lymphoma are at increased risk of dysglycemia due to disease-related and treatment-associated metabolic alterations. This study aimed to characterize fasting capillary glucose patterns in patients with lymphoma undergoing routine capillary fasting blood glucose assessment before fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). Materials and Methods: Consecutive patients with lymphoma undergoing clinically indicated FDG PET/CT at the University Hospital Zurich were included. Capillary fasting blood glucose (cFBG) was measured before tracer administration and categorized according to American Diabetes Association fasting glucose thresholds. Additional analyses were performed in patients examined before 11:00 AM and in patients without known diabetes mellitus. Multivariable linear regression was used to identify factors associated with cFBG. Results: The cohort included 210 consecutive patients with lymphoma (median age 64 years, IQR 48–73; 44% female, 92/210; median BMI 24 kg/m², IQR 22–28). Known diabetes mellitus was present in 12% (25/210). Median cFBG was 104 mg/dL (IQR 95–115; 5.8 mmol/L, IQR 5.3–6.4). Overall, 64% (135/210) had cFBG values above the normal range (≥100 mg/dL; ≥5.6 mmol/L). Among patients examined before 11:00 AM, this proportion was 69% (81/117). After excluding patients with known diabetes mellitus, 60% (111/185) had cFBG values above the normal range, and 7% (13/185) had values ≥126 mg/dL (≥7.0 mmol/L). In multivariable analysis, BMI and regular exercise were independently associated with cFBG. Conclusions: Almost two-thirds of patients with lymphoma undergoing FDG PET/CT had cFBG values above the normal range, including 60% of those without known diabetes mellitus. These findings highlight the need for improved dysglycemia screening and management in lymphoma care. Full article

Survivors of childhood acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and non-Hodgkin lymphoma (NHL) are at risk of developing long-term adverse effects after survival. This study examined observed proportions of perceived mental distress, fatigue, and executive function (EF) impairment in adult childhood cancer survivors (CCSs) of ALL, AML, and NHL. Secondly, it examined the association between perceived EF impairment and mental distress or fatigue. Participants (n = 132; 57% female) were recruited from two major Norwegian hospitals. Self-report questionnaires included the Behavior Rating Inventory of Executive Function, Adult Version, the Hopkins Symptom Checklist-25, and the Fatigue Severity Scale. Proportions exceeding established clinical thresholds were calculated, and groups were compared using Pearson’s chi-squared test and Newcombe confidence intervals. Overall, 49% and 41% of participants met the clinical thresholds for depression and anxiety; 43% for fatigue; and 28% for EF impairment. Perceived EF impairment was significantly associated with mental distress and fatigue. Mental distress, fatigue, and EF impairment are commonly reported and distressing late effects among CCSs of ALL, AML, and NHL. Follow-up care focusing on neurocognitive and psychological outcomes is important for the long-term functioning and well-being of this survivor group. Targeted neurocognitive rehabilitation may represent a key component of follow-up care. Full article

After first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), 20–30% of patients with diffuse large B-cell lymphoma (DLBCL) have relapsed or refractory disease. Semi-quantitative volume parameters on [18F]Fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT), performed at diagnosis, could represent variables with prognostic influence. We retrospectively analyzed 53 consecutive patients, treated between 2016 and 2022. Semi-quantitative metabolic parameters, assessed by the software LIFEx, included total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), Dmax and DmaxVox. All cases received R-CHOP/CHOP-like regimens with curative intent. The International Metabolic Prognostic Index (IMPI) was low in 43/53 cases (81.1%). CR was achieved in 49/53 patients (92.4%); 7/53 (13.2%) relapsed after achieving a CR. For the entire cohort, 2-year PFS and OS were 84.9% and 90.6%, respectively, while 5-year PFS and OS were 65.5% and 77.6%, respectively. IPI score, B symptoms, TMTV, Dmax and DmaxVox were associated with reduced PFS in an exploratory univariate analysis. IPI score was the only variable for which we found a significant association with reduced OS. In this exploratory analysis in a small, event-limited population, we suggest the baseline, semi-quantitative metabolic parameters of PET/CT at diagnosis could contribute to defining tumor burden and to predict PFS for DLBCL patients. Full article

Background and Purpose: Contrast-enhanced MRI findings of leptomeningeal enhancement (LME) indicate dysfunction of the blood–brain barrier and can be seen in various neoplastic, infectious, and inflammatory conditions. To the best of our knowledge, systematic evaluation of different patterns of LME remains limited. This case series aims to describe and compare MRI patterns of leptomeningeal enhancement across diverse etiologies. Materials and Methods: We retrospectively evaluated six patients with known or suspected leptomeningeal disease on contrast-enhanced MRI studies of the brain and/or spine with regard to pattern, distribution, localization, and thickness of LME. Results: The patterns of neoplastic causes (glioblastoma, lymphoma, and adenocarcinoma) were characterized by diffuse, thick, and nodular LME, as well as frequently affected cranial nerve and nerve-root involvement. The infections caused various patterns: in cases of tuberculous meningitis, LME was focal and basal in nature, accompanied by parenchymal lesions; whereas in cases of HIV-related meningitis, LME was diffuse and exhibited a pseudocisternogram pattern. The inflammation (suspected neurosarcoidosis) revealed smooth-to-nodular LME with spinal and suprasellar involvement. Conclusions: Although LME patterns are not specific, systematic evaluation of enhancement characteristics may provide useful diagnostic clues and assist in narrowing the differential diagnosis. Full article

Background/Objectives: Anaplastic lymphoma kinase (ALK) fusion is a driver gene translocation detected in 3–5% of patients with non-small-cell lung cancer (NSCLC). Next-generation sequencing (NGS)-based tests are the standard of care for detecting actionable gene alterations; however, false negatives remain a concern. Immunohistochemical staining is another reliable, rapid, and low-cost method for detecting ALK fusions. Previous studies have reported high concordance with NGS, although further studies are needed to draw definitive conclusions. Methods: A retrospective analysis was conducted on consecutive patients with NSCLC who were tested using the Oncomine Dx Target Test (ODxTT), an amplicon-based DNA and RNA NGS test for NSCLC, and ALK-immunohistochemistry (IHC) at our institution between 8 August 2019 and 11 April 2025. Results: Of 919 eligible patients included in this study, ALK fusion was detected in 30 (3.26%) patients, whereas ALK-IHC was positive in 35 (3.80%) patients. The concordance and κ coefficient of the two tests were 99.4% and 0.920, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of ALK-IHC for ODxTT were 100%, 99.4%, 85.7%, and 100%, respectively. Five discordant patients were NGS negative and IHC positive. Among the five discordant cases, one had a false-negative NGS result, whereas the remaining four had false-positive ALK-IHC results, including three patients with neuroendocrine carcinomas. Conclusions: ALK-IHC shows diagnostic accuracy comparable to ODxTT, although prudent interpretation is needed for patients without adenocarcinoma. Our findings suggest the complementary role of ALK-IHC alongside NGS-based testing, particularly in patients with a high pre-test probability of harbouring ALK fusions. Full article

Diabetes mellitus (DM) may influence susceptibility to ocular infection and inflammatory phenotypes; however, disease-specific DM prevalence across uveitis etiologies has not been well characterized. We evaluated DM prevalence across major uveitis entities in a large single-center cohort and compared observed prevalence estimates with age-specific national estimates from Japan. A total of 3163 adult patients out of 4751 patients newly diagnosed with uveitis at the Tokyo Medical University Hospital between 2004 and 2023 were included in the final analysis after excluding patients without DM-related laboratory parameters, those who declined to participate through the institutional opt-out procedure, pediatric patients, and patients with diabetic iritis. DM was defined as an HbA1c level of 6.5% or higher, current treatment for DM, or a random blood glucose level of 200 mg/dL or higher. For reference comparisons with national data, we analyzed seven adult entities with sufficient sample size. For each entity, expected DM prevalence was based on the corresponding national age-stratum estimate according to the mean age category of that entity. Observed and expected DM prevalence estimates were compared using Fisher’s exact test. Multivariable modified Poisson regression with robust variance estimation was used to estimate adjusted prevalence ratios (aPRs) for DM prevalence, including age, sex, and individual uveitis entities as covariates. Overall, 166 of 3163 patients (5.3%) had DM. DM prevalence differed substantially by etiology, ranging from 18.0% in endophthalmitis to 1.8% in Behçet disease. Selected infectious uveitis showed a higher crude prevalence of DM than selected noninfectious uveitis (10.4% vs. 3.8%; p < 0.01). In comparisons with corresponding national age-stratum estimates, the observed prevalence estimates of DM in endophthalmitis and herpetic iritis did not differ significantly from the expected national prevalence estimates, whereas acute retinal necrosis, intraocular lymphoma, sarcoidosis, and Behçet disease showed a significantly lower prevalence than expected. In the multivariable analysis, older age (aPR per 10-year increase, 1.49; 95% CI, 1.33–1.67; p < 0.001) and male sex (aPR, 2.11; 95% CI, 1.40–3.19; p < 0.001) were independently associated with DM prevalence, whereas individual uveitis entities were not significantly associated after adjustment for covariates. DM prevalence in uveitis is heterogeneous and disease-specific. Although selected infectious uveitis showed a higher crude prevalence of DM, comparisons with corresponding national age-stratum estimates suggested that some of the differences reflected the underlying age structure. Older age and male sex were the strongest independent correlates of DM prevalence. Full article

Diffuse large B-cell lymphoma (DLBCL) is a biologically heterogeneous mature B-cell neoplasm whose classification, prognosis, and therapy have been reshaped by advances in genomic, transcriptomic, epigenomic, single-cell, and spatial profiling technologies. This review focuses on how these approaches have refined the molecular landscape of DLBCL, including recurrent chromosomal translocations, tumor-suppressor alterations, oncogenic signaling pathways, and tumor-microenvironment programs. Cell-of-origin (COO) frameworks remain clinically useful. However, contemporary models extend beyond conventional germinal center categories by incorporating probabilistic genetic subtypes, expression-defined high-risk states, and spatially resolved lymphoma-cell and immune-cell ecosystems. These high-resolution methods clarify intratumoral heterogeneity, identify biologically distinct subgroups, and inform prognosis and therapeutic selection. The review also summarizes how tumor-intrinsic biology and the tumor-microenvironment (TME) shape responses to frontline therapy, targeted agents, antibody-drug conjugates, bispecific antibodies, and CD19-directed CAR T-cell therapy. Particular emphasis is placed on product-specific evidence in relapsed/refractory disease, rational sequencing of immunotherapies, and emerging biomarkers such as circulating tumor DNA-based measurable residual disease (ctDNA-MRD). Together, these developments support a shift from COO-centric classification toward dynamic, biology-driven models that incorporate tumor-intrinsic and microenvironmental determinants to guide personalized therapy in DLBCL. Full article

Background/Objectives: Outcomes after CD19-directed chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) aggressive large B-cell lymphoma (aLBCL) remain heterogeneous. Tumor genomic biomarkers, such as TP53 alteration, MYC/BCL2/BCL6 rearrangement-defined double-hit or triple-hit lymphoma (DHL/THL), cell of origin (COO), and complex karyotype, are established or candidate prognostic factors in conventionally treated lymphoma, but their relevance after CAR T-cell therapy is uncertain. We conducted a systematic review with exploratory meta-analysis of biomarker-stratified outcomes after CD19 CAR T-cell therapy in aLBCL. Methods: We searched MEDLINE, Embase, and Web of Science/BIOSIS (April 2026), with targeted PubMed citation lookup during full-text retrieval (PROSPERO CRD420261350514). Eligible studies enrolled adults with R/R disease treated with protocol-eligible CD19 CAR T-cell therapy and reported prespecified tumor genomic biomarkers with stratified outcomes. Random-effects models, using restricted maximum-likelihood estimation with Hartung–Knapp–Sidik–Jonkman (HKSJ) adjustment, were fitted when at least three comparable, non-overlapping studies provided extractable data. Results: After duplicate removal, 182 records were screened, 37 were assessed for eligibility, and 26 studies were included in the qualitative synthesis; 10 contributed to 4 pooled analyses. DHL/THL-positive disease was associated with worse unadjusted overall survival (OS) (hazard ratio [HR] 1.52; 95% confidence interval [CI], 1.21–1.89; 95% prediction interval (PI), 0.56–4.08), and non-Germinal center B-cell-like (GCB)/ABC COO with worse adjusted progression-free survival (PFS) (HR 1.44; 95% CI, 1.04–2.00; 95% PI, 0.86–2.43). The complete-response analyses for TP53 alteration (OR 1.30; 95% CI, 0.01–156.60) and COO (OR 1.27; 95% CI, 0.24–6.61) were statistically uninformative. No study permitted evaluation of complex karyotypes. Conclusions: Biomarker-stratified evidence after CD19 CAR T-cell therapy is sparse and inconsistently reported. DHL/THL status and non-GCB/activated B-cell-like (ABC) COO showed exploratory survival signals, whereas the TP53 and COO complete-response analyses were uninformative. These biomarkers remain hypothesis-generating rather than validated predictors of CAR T-cell outcome, and standardized, prospective biomarker-stratified reporting is needed. Full article

Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation and is mechanistically distinct from apoptosis, necrosis and pyroptosis. Increasing evidence indicates that ferroptosis plays a critical role in cancer biology, including lymphoproliferative disorders, where chronic redox imbalance, dysregulated iron metabolism, and metabolic rewiring create a permissive environment for ferroptotic vulnerability. In these malignancies, altered iron handling, elevated reactive oxygen species, and a strong reliance on antioxidant systems such as glutathione and glutathione peroxidase 4 tightly control ferroptotic sensitivity. Dysregulation of key components, including SLC7A11, lipid metabolism pathways, and intracellular iron homeostasis, further shapes the susceptibility of malignant lymphoid cells to ferroptosis. Importantly, emerging preclinical studies suggest that therapeutic targeting of ferroptosis may overcome resistance to conventional chemotherapy, targeted agents, and immunotherapy, offering novel opportunities particularly in relapsed or refractory disease. This review provides a comprehensive overview of the molecular mechanisms governing ferroptosis in lymphoproliferative disorders, highlights the interplay between ferroptosis and major cellular and metabolic pathways, and discusses current and emerging strategies to pharmacologically induce ferroptosis, with an emphasis on biomarker-driven clinical translation. Full article