Search Results (697)

Skin diseases frequently coexist with other disorders, such as metabolic syndrome, diabetes mellitus, depression, psoriatic arthritis, and cardiovascular disease. Altered levels of distinct chemokines, like CCL5/RANTES, CXCL12/SDF-1a, CCL7/MCP-3, CCL2/MCP-1, CXCL1/GROa, and the eotaxin family, contribute to the development and/or exacerbation of inflammation, which is a common feature of numerous skin diseases as well as metabolic syndrome. The pathological and molecular connections between chronic inflammatory skin diseases and metabolic syndrome are increasingly recognized as being driven by shared inflammatory pathways, oxidative stress, and adipokine dysregulation. While systemic inflammation acts as a common thread, the precise mechanisms for some conditions remain partially understood. Nevertheless, the exact pathological and molecular connections between skin diseases (i.e., psoriasis, atopic dermatitis, pemphigus vulgaris, acute and chronic spontaneous urticaria, bullous pemphigoid, squamous cell carcinoma, alopecia areata, systemic sclerosis, discoid lupus erythematosus, diffuse large B-cell lymphoma) and metabolic syndrome are not yet fully understood. This narrative review summarizes the robust association between various chronic inflammatory skin diseases and metabolic syndrome in the context of pro-inflammatory chemokines. Full article

Background/Objectives: Central Nervous System (CNS) relapse represents a severe and often fatal complication of Diffuse Large B-Cell Lymphoma (DLBCL). This study aimed to evaluate clinical, biological, and treatment-related factors associated with progression-free survival (PFS) until CNS relapse in patients with DLBCL. Methods: A retrospective cohort study was conducted using clinical data from adult DLBCL patients evaluated and treated at the Regional Institute of Oncology, Iași, Romania, between 2015 and 2023. Associations between clinical, biological, and treatment-related variables and CNS relapse were evaluated using univariate and multivariable Cox proportional hazards models, Fine–Gray competing-risk analyses, and propensity score-based methods to address confounding by indication for CNS prophylaxis. Results: Twenty-six CNS relapse events (6.3%) and 72 deaths without prior CNS relapse occurred over a median follow-up of 12 months. In the prespecified reduced multivariable Cox model, non-R-CHOP regimens (HR 4.57, 95% CI 1.67–12.52; p = 0.003) and high CNS-IPI scores (HR 4.70, 95% CI 1.14–19.46; p = 0.033) were independently associated with CNS relapse. The 20-month cumulative incidence of CNS relapse was 7.0% in the R-CHOP-like group versus 35.2% in the non-R-CHOP group (Gray’s test p < 0.001). Fine–Gray modeling confirmed the association for non-R-CHOP regimens (SHR 3.38, 95% CI 1.21–9.45; p = 0.02). Cell-of-origin subtype, double-expressor phenotype, and Ki-67 were not significantly associated with CNS relapse. Conclusions: High CNS-IPI and treatment with non-R-CHOP regimens independently predicted earlier CNS relapse. Future multicenter studies with molecular profiling are needed to refine CNS risk stratification. Full article

The high incidence of thrombosis in lymphoma is largely due to chronic inflammation and endothelial dysfunction. To elucidate the mechanisms underlying thrombus formation and fibrinolysis, we investigated interactions between circulating endothelial cells and peripheral blood mononuclear cells (MNCs), along with inflammatory signaling pathways, in patients with follicular lymphoma (FL), Hodgkin lymphoma (HL), and diffuse large B-cell lymphoma (DLBCL), independent of the presence of thrombosis, compared to healthy controls by flow cytometry, immunoblotting, and fluorometric assays. We observed increased tissue factor (TF) expression on CD31+ endothelial cells in DLBCL and FL. In DLBCL, inducible nitric oxide synthase expression was elevated in MNCs, while reduced nitrite levels correlated with an advanced clinical stage in patients with thrombosis. In lymphoma, nuclear factor kappa B (NFκB) signaling was activated in MNCs, while signal transducer and activator of transcription 3 (STAT3) activation was increased in DLBCL with thrombosis. Trans-endothelial migration of MNC was enhanced in HL, FL and DLBCL with thrombosis and reduced by inflammatory cytokine tumor necrosis factor alpha (TNF-α) that promoted platelet aggregation like interleukin-6 (IL-6) in HL and FL. Fibrinolytic analyses showed reduced tissue type plasminogen activator in lymphoma, whereas increased urokinase-type plasminogen activator (uPA) was linked to poorer total survival in DLBCL with thrombosis, suggesting a compensatory role in early thrombus resolution. These findings indicate that chronic inflammation promotes endothelial activation, dysregulated fibrinolysis, and increased vascular permeability, contributing to heightened thrombotic risk. This study provides mechanistic insight into lymphoma-associated thrombosis and identifies TF, uPA, and the inflammatory signaling pathways as potential biomarkers and therapeutic targets. Full article

Background: Malignant lymphoma is the most common hematological malignancy; however, primary central nervous system lymphoma accounts for only a small percentage of non-Hodgkin lymphoma (NHL). Among these, primary cauda equina lymphoma (CEL) is extremely uncommon. Its rarity and atypical clinical presentation often make diagnosis challenging. Case Presentation: An 80-year-old man presented with progressive gait disturbance, lower-extremity weakness, and numbness. MRI revealed diffuse swelling and homogeneous gadolinium enhancement of the cauda equina at T12–L1; additionally, CSF cytology identified malignant lymphocytes. Open biopsy confirmed a diagnosis of diffuse large B-cell lymphoma. At diagnosis, the patient was classified as Ann Arbor stage IV, and the clinical parameters corresponded to a high-risk International Prognostic Index (IPI) category. The patient received five courses of immunochemotherapy with rituximab, methotrexate, vincristine, and procarbazine (R-MPV), resulting in marked radiological improvement and functional recovery, achieving a complete response. However, consolidation therapy was discontinued as the patient did not wish to continue. Unfortunately, intracranial relapse occurred four months later, and the patient ultimately succumbed to infectious complications. Only 29 cases of primary CEL have been reported. For all cases, a biopsy with histopathological examination is required for a definitive diagnosis. Currently, combined chemotherapy and radiotherapy are considered the standard treatment. This case was diagnosed through nerve biopsy with cauda equina at T12 to L1 levels, and immunochemotherapy successfully reduced the lesion while improving lower extremity function. Conclusions: Despite the considerable burden on patients, nerve biopsy is necessary for primary CEL to obtain a diagnosis and an early therapeutic approach for both neurological and vital prognoses. Full article

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) and high-grade follicular lymphoma (FL) are aggressive B-cell malignancies predominantly affecting older adults. R-CHOP remains the frontline standard of care, with frail and elderly patients requiring attenuated regimens such as R-mini-CHOP. Real-world comparative data in elderly and Hispanic populations remain limited. We aimed to evaluate outcomes of R-mini-CHOP versus R-CHOP in elderly patients and to explore potential differences by ethnicity. Methods: Single-center retrospective analysis of adult patients older than 70 years with DLBCL and high-grade FL, treated between January 2014 and June 2025. Clinical characteristics, treatment responses, and survival outcomes were analyzed. The overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Results: A total of 136 patients were included (72 R-mini-CHOP; 64 R-CHOP). Patients receiving R-mini-CHOP were older (median 82 vs. 74 years) and had higher-risk features. Overall response rates were 88.7% and 92.6% in the R-mini-CHOP and R-CHOP groups, respectively. Two-year OS was 79.3% for R-mini-CHOP and 76.7% for R-CHOP. Median OS and PFS were not reached in either group. Elevated lactate dehydrogenase (LDH) was associated with an inferior response. We identified a trend toward better response with R-CHOP in Hispanic patients, although this was not statistically significant. Conclusions: In this real-world cohort, R-mini-CHOP achieved response and survival outcomes comparable to R-CHOP despite worse baseline characteristics. These findings support the use of dose-attenuated therapy in frail and elderly patients and suggest that equitable access to care may mitigate ethnic disparities in outcomes. Full article

Background: Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) exhibit substantial heterogeneity, reflecting the diversity of the germinal center (GC). Histologic transformation of FL to DLBCL is associated with poor prognosis, yet robust biomarkers predicting transformation remain limited. Methods: We integrated single-cell DNA sequencing, single-cell RNA sequencing, and spatial transcriptomics in diagnostic lymph-node biopsies from non-transformed FL (ntFL), transformed FL (tFL), and DLBCL to characterize clonal states and immune niches in GC lymphomas. T-cell signatures associated with transformation were evaluated in an independently published single-cell FL dataset. Results: Transcriptional profiling revealed similarities between tFL and DLBCL, consistent with a GC-related malignant program. The tFL microenvironment showed enrichment of exhausted CD4⁺ regulatory and CD8⁺ effector T cells, together with CD4⁺ follicular helper T cells (Tfh) displaying an adhesion-related phenotype. Spatial analysis suggested increased proximity of exhausted/immunosuppressive T cells and enhanced Tfh-B-cell interactions in tFL compared with ntFL. These immune signatures were also observed in an external cohort and were associated with early transformation. In addition, clonal hematopoiesis-associated mutations were detected in microenvironmental cells across samples, suggesting a potential contribution to the lymphoma microenvironment. Conclusions: This work demonstrates the feasibility of integrating single-cell and spatial analyses in GC lymphomas and provides a framework for investigating tumor heterogeneity and immune organization. These findings may inform future studies on biomarker development and the rational design of immunotherapies. Full article

Extracellular vesicles (EVs), as key mediators of intercellular communication, play multifaceted roles in the pathogenesis, treatment, drug resistance, and monitoring of B-cell non-Hodgkin lymphomas (B-NHLs), including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). EVs derived from lymphoma cells or tumor microenvironment cells carry diverse cargoes such as proteins, microRNAs (miRNAs), and viral oncoproteins, which regulate tumor progression by modulating signaling pathways related to cell proliferation, invasion, apoptosis, autophagy, and immune suppression. In terms of treatment, accumulating evidence suggests that EVs may be associated with the efficacy of classical regimens such as R-CHOP, and they also hold potential as therapeutic targets and drug delivery vehicles for B-NHL. They contribute to drug resistance by altering the expression of key molecules or reshaping the tumor niche. Additionally, EV-derived biomarkers enable non-invasive diagnosis and monitoring of treatment response and prognosis. This review summarizes the latest research progress on the roles of EVs in major B-NHL subtypes, aiming to provide new insights for the development of innovative diagnostic and therapeutic strategies for B-NHL. Full article

Background and Clinical Significance: Burkitt lymphoma is an aggressive form of non-Hodgkin lymphoma of B-cell origin, caused by a MYC gene translocation on chromosome 8. There are three clinical subtypes, of which the sporadic subtype is most prevalent in the United States. Sporadic Burkitt lymphoma is diagnosed at a median age of 30 years and commonly manifests as bulky abdominal lesions, most often involving the ileocecal region. Pancreatic involvement is uncommon, and presentation as acute pancreatitis secondary to Burkitt lymphoma is exceedingly rare. Case Presentation: We present a case of a young male who presented with epigastric pain, nausea, and vomiting. He had a diffusely tender abdomen and elevated lipase levels. On imaging, he was found to have large retroperitoneal and intraperitoneal masses, contiguous with an enlarged pancreas. Burkitt lymphoma was confirmed upon biopsy of duodenal and gastric masses via endoscopic ultrasound. MRI brain and testicular ultrasound revealed unilateral fifth cranial nerve and bilateral testicular involvement, respectively. His course was complicated by bowel perforation requiring urgent surgery. However, he achieved complete remission with dose-dense systemic and intrathecal chemotherapy. Conclusions: This case highlights the diverse presentations of Burkitt’s lymphoma and a favorable prognosis with treatment. Clinicians should maintain a high index of suspicion for a malignant etiology of acute pancreatitis in patients without classic risk factors. Full article

Background and Clinical Significance: Diffuse Large B-Cell Lymphoma (DLBCL) is a morphologically and molecularly heterogeneous lymphoproliferative disorder that originates from a clonal B-cell ancestor. Patients usually present with rapidly enlarging lymph nodes or mass(es) at single or multiple sites. Generally, 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography with computed tomography (PET-CT) is performed post-treatment to evaluate remission status, especially in radiologically residual tumors. Myofibroblastoma (MFB) is a benign mesenchymal tumor of the mammary stroma composed of fibroblasts and myofibroblasts. These entities do not often present concurrently. Case presentation: The patient was an 80-year-old man with a history of stage IV-BS Diffuse Large B-Cell Lymphoma (DLBCL) with a high-risk International Prognostic Index (IPI). The patient underwent treatment with a six-cycle R-CHOP regimen. Immediately after the last cycle, an 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography with computed tomography (PET-CT) scan revealed a nodular solid lesion with a faintly increased metabolic standardized uptake value (SUVmax) of 3 in the upper outer quadrant of his left breast. A biopsy of the breast lesion was performed, and it revealed a benign mesenchymal tumor, specifically a Myofibroblastoma. The patient has not presented any symptoms or complications since surgery (12 months) and remains in complete remission (CR). Conclusions: Given the potential diagnostic pitfalls and therapeutic implications of residual tumors in the context of DLBCL, a conscientious evaluation by a multidisciplinary team (MDT) is highly recommended. Full article

Background/Objectives: Lymphoproliferative disorders (LPDs) are adverse effects of methotrexate (MTX) prescribed for rheumatoid arthritis (RA). Sjögren’s disease (SjD), for which the presence of anti-Ro/SS-A antibodies (Abs) is a diagnostic criterion, might accompany RA and be a risk factor for LPDs. We conducted a retrospective study to analyze the effects of SjD or anti-Ro/SS-A Ab positivity on the clinical course of patients with RA complicated by LPDs. Methods: We retrospectively analyzed 25 patients in our department who had RA complicated by LPDs, specifically collecting clinical information regarding the complications of SjD and positivity for anti-Ro/SS-A Abs. Results: In total, 25 patients with RA were included in this study, 3 of which were diagnosed with SjD by attending physicians based on sicca symptoms and positiveness of anti-Ro/SS-A antibodies. No significant differences in clinical characteristics except for SjD diagnosis given by attending physicians were found between the patients positive for anti-Ro/SS-A Abs and the patients negative for anti-Ro/SS-A Ab. The most common histologic LPD subtype was diffuse large B cell lymphoma, while mucosa-associated lymphoid tissue lymphoma, the histologic subtype often diagnosed as SjD-LPD, was found in only one patient, who was positive for anti-Ro/SS-A Abs without an SjD diagnosis. There were no significant differences in the intervals between the RA and LPD diagnoses and those of SjD and anti-Ro/SS-A Ab positivity. Conclusions: While the rate of anti-Ro/SS-A Ab positivity in the study population seemed to be higher than that in the general RA population, any potential effects of SjD on RA-LPD development were not ascertained in this study. Full article

Background: Glofitamab is a bispecific antibody engaging CD3 on T-cells and CD20 on B-cells. Glofitamab is approved for the treatment of relapsed, refractory diffuse large B-cell lymphoma (R/R DLBCL). Lymphocyte-activation gene 3 (LAG3) and T-lymphocyte-associated protein 4 (CTLA4) are immune checkpoint receptors with inhibitory effects on T-cell activity. There are several common germline variants of both receptor genes. Methods: Here, we evaluate clinical outcomes in R/R DLBCL patients treated with glofitamab according to the single-nucleotide polymorphisms LAG3 rs870849 and CTLA4 rs231775. Results: While there was no apparent association of CTLA4 genotype with glofitamab treatment outcomes, significant differences emerged in LAG3 rs870849 carriers with extended progression-free and overall survival in homozygous LAG3 T455, intermediate PFS and OS in heterozygous LAG3 I455T, and short PFS and OS in homozygous LAG3 I455 carriers. Conclusions: LAG3 rs870849 may be a prognostic response marker in R/R DLBCL treated with glofitamab. Full article

Background: Primary endometrial lymphomas (PELs) are exceedingly rare and diagnostically challenging lesions. Objective: To assess the clinicopathologic features of PELs. Methods: We adhered to the PRISMA-2020 guidelines for reporting systematic reviews. A PubMed literature search (1956–2025) was conducted using keyword combinations including “endometrium” and “lymphoma,” “lymphoid proliferation,” or “lymphoproliferative lesions.” Only original articles published in the English peer-reviewed journals were considered. The inclusion criteria were: (i) studies involving human subjects, and (ii) studies published in the English language. Reviews, editorials, meeting abstracts, and non-English publications were excluded. Results: We identified 42 studies for our analysis, collectively reporting 58 cases of PELs. Abnormal uterine bleeding was the main complaint. Non-Hodgkin lymphoma (57 cases) and Hodgkin lymphoma (one case) were identified. In most cases, lymphoma was the sole lesion. In five cases, lymphoma coexisted with, preceded, or followed endometrial carcinoma. Histologically, PELs either diffusely involved the endometrium (50 cases) or were localized to endometrial polyps (eight cases). Marginal zone lymphoma (MZL) was the most frequently reported type, followed by diffuse large B-cell lymphoma (DLBCL). Other rare types included intravascular large B-cell lymphoma, NK/T-cell lymphoma, T-cell lymphoma, and low-grade B-cell lymphoma. Conclusions: Our study indicates that MZL and DLBCL were the most common types of PELs. Other extremely rare subtypes were also identified. Moreover, some PELs developed in the background of endometrial polyps and, in exceptional cases, in association with endometrial carcinoma. Radiological findings were critical for provisional diagnosis, staging, and follow-up. Key modalities included ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and 18F-fluoro-2-deoxyglucose positron emission tomography/CT (18F-FDG PET/CT). Full article

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and remains incurable in approximately 30–40% of patients despite advances in immunochemotherapy. Although gene expression profiling has improved risk stratification, there is an ongoing need for non-invasive, cost-effective, and clinically practical biomarkers to identify patients at high risk of treatment resistance or relapse (R/R). Systemic inflammation plays a pivotal role in DLBCL pathogenesis, impacting both tumor progression and treatment response. The C-reactive protein–albumin–lymphocyte (CALLY) index, integrating markers of inflammation, nutritional status, and immune competence, has demonstrated prognostic relevance in solid tumors; however, its relevance in hematologic malignancies remains unexplored. Methods: We retrospectively analyzed 180 adults with newly diagnosed DLBCL, NOS (not otherwise specified) who received frontline rituximab-based immunochemotherapy (R-CHOP or CHOP-like regimens) between January 2014 and December 2019 at three tertiary centers in Serbia. The median age was 67 years (IQR 59–73), and 56.1% were female. Receiver operating characteristic (ROC) analysis determined 6.5 as the optimal CALLY index cut-off (AUC 0.744, 95% CI 0.670–0.817; p < 0.001). Results: A low CALLY index (<6.5) was significantly associated with adverse clinical features, including anemia, elevated lactate dehydrogenase and β2-microglobulin, poor ECOG performance status, bulky disease, advanced stage, and unfavorable IPI, R-IPI, and NCCN-IPI scores (all p < 0.001). In contrast, no associations were observed with tumor subtype, immunophenotype, or comorbidities. Furthermore, patients with CALLY <6.5 showed lower overall response rates to treatment (59.6% vs. 85.5%, p < 0.001) and higher relapse rates (21.0% vs. 6.2%, p = 0.014). They also experienced reduced 3- and 5-year overall survival (OS) and event-free survival (EFS) (all p < 0.001). In multivariate analysis, a low CALLY index independently predicted poorer OS (HR 2.04, 95% CI 1.13–3.67; p = 0.017) and EFS (HR 1.89, 95% CI 1.13–3.14; p = 0.015). In addition, it independently identified patients at risk of relapsed/refractory (R/R) disease (OR 2.50, 95% CI 1.02–10.10; p = 0.04), outperforming standard prognostic indices. Conclusions: The CALLY index is a simple, low-cost, and widely accessible biomarker that independently predicts prognosis in DLBCL, NOS. It outperforms standard indices in identifying R/R cases. The CALLY index may enhance risk stratification and guide individualized treatment strategies. Full article

Bone marrow involvement in B-cell non-Hodgkin lymphoma is an adverse prognostic factor; therefore, its detection is necessary at the time of diagnosis and during follow-up. This study evaluates the concordance between flow cytometry (FC) and bone marrow biopsy (BMB) in detecting bone marrow involvement in B-cell non-Hodgkin lymphomas as well as their prognostic relevance in a Chilean cohort. A total of 202 samples from 172 patients with diffuse large B-cell (DLBCL), follicular (FL), marginal-zone (MZL), and mantle cell (MCL) lymphoma were retrospectively analyzed; all patients underwent simultaneous BMB and FC. Bone marrow involvement was identified in 29% of samples via BMB and in 40% via FC, with an overall concordance of 89% (kappa: 0.75), which was lower in mantle cell lymphoma. Eleven percent of cases showed BMB-FC+ discordance, generally associated with low tumor burden. In survival analyses, the BMB+/FC+ group exhibited shorter overall and progression-free survival, and concordant involvement was associated with a higher risk of mortality and progression, particularly among patients with an intermediate or high IPI. Involvement detected exclusively by FC did not have a significant prognostic impact. These findings support the role of FC as a complementary or alternative diagnostic tool in settings with limited resources, improving sensitivity for detecting bone marrow involvement without compromising clinical relevance. Full article

Introduction: Central nervous system (CNS) involvement is reported to represent 5% of extranodal diffuse large B cell lymphoma (DLBCL) at diagnosis. To stratify patients’ risk of CNS involvement, the CNS-International Prognostic Index (CNS-IPI) score was developed. Serum uric acid level has not been incorporated into IPI or CNS-IPI score and its correlation with CNS-IPI risk groups and the CNS relapse has not been studied to date. Therefore, we aimed to retrospectively analyze the relationship between uric acid levels and CNS relapse risk in patients with newly diagnosed adult DLBCL. Methods: Ninety-four adult newly diagnosed DLBCL patients were retrospectively assessed via electronic records and patient files. Demographic data, IPI and CNS-IPI scores, hematologic parameters, serum lactate dehydrogenase, beta-2 microglobulin, serum uric acid and creatinine levels at diagnosis were recorded for analysis. Uric acid levels were compared between CNS-IPI low-intermediate and high groups and cumulative incidence of CNS relapses were analyzed between normal and elevated uric acid levels. Results: Uric acid levels were found to be significantly higher in CNS-IPI high-risk patients (p = 0.008). Elevated serum uric acid levels at diagnosis were significantly associated with high CNS-IPI risk in the logistic regression analysis (OR 1.34, 95% CI 1.05–1.78, p = 0.047). Uric acid also higher than 5.39 mg/dL showed a discriminatory ability in ROC analyses (AUC 0.633, 95% CI 0.495–0.771, p = 0.05). In the competing risks regression analysis, accounting for non-CNS-related death and progression as the competing events, CNS-IPI subgroups and uric acid levels were not significantly associated with the cumulative incidence of CNS relapse (SHR 0.81, 95% CI 0.12–5.59; Fine–Gray, p = 0.834), (SHR 0.55, 95% CI 0.09–3.47; Fine–Gray, p = 0.526), respectively. Conclusions: Even though uric acid levels are significantly higher and showed a discriminatory ability to detect the CNS-IPI high subgroup, elevated uric acid levels could not predict the CNS relapses. Full article