Search Results (1,141)

Background: Primary lymphoma of peripheral nerves (PLPN) is a rare extranodal non-Hodgkin lymphoma that mimics benign nerve conditions, leading to diagnostic delays. This systematic review evaluates the clinical, radiological, and pathological features of PLPN, alongside diagnostic and therapeutic strategies. Materials and Methods: A systematic search was conducted across PubMed, Scopus, and Web of Science, and identified 23 studies reporting 27 cases of PLPN. Data on demographics, clinical presentation, diagnostics, treatment, and outcomes were extracted and synthesized qualitatively due to study heterogeneity. Results: The sciatic nerve was most involved (48.15%), followed by the ulnar (18.5%) and radial nerves (18.5%). The median age at diagnosis was 58 years, with symptoms including motor deficits (88.9%), sensory disturbances (74.1%), and pain (70.4%). B-cell lymphomas accounted for 81.5% of cases, predominantly diffuse large B-cell lymphoma. MRI findings were non-specific; however, diffusion-weighted imaging (DWI) showed diagnostic potential. Treatments included combination therapies (51.9%), chemotherapy (25.9%), and surgery. Complete remission was achieved in 70.8%, with a 2-year survival rate of 83.3%. Conclusions: PLPN is rare but likely underdiagnosed. Early recognition requires multidisciplinary collaboration, advanced imaging, and standardized protocols. Future research should focus on molecular characterization, diagnostic criteria, and treatment optimization to improve outcomes for this challenging condition. Full article

Background/Objectives: Non-Hodgkin lymphoma (NHL) is a group of blood cancers that arise in the lymphatic nodes and other tissues after an injury to the DNA of B/T lineage and NK lymphocytes. Recently, we reported that incomptine A (IA) has in vivo antilymphoma properties. This research aimed to evaluate the effects of IA in the treatment of NHL using antilymphoma activity, Tandem Mass Tag (TMT), and bioinformatics approaches. Methods: The antilymphoma activity of IA was tested on male Balb/c mice inoculated with U-937 cells. Also, TMT, gene ontology enrichment, Reactome pathway, Kyoto Encyclopedia of Gene and Genomes pathway, molecular docking, toxicoinformatic, and pharmaceutical analyses were performed. Results: By TMT analysis of the altered levels of proteins present in the lymph nodes of Balb/c mice with NHL and treated with IA, we identified 106 significantly differentially expressed proteins (DEPs), including Il1rap, Ifi44, Timd4, Apoa4, and Fabp3 as well as Myh3, Eno 2, and H4c11. Among these, the Fhl1 result was the most important cluster altered and a potential core target of IA for the treatment of NHL. Network pharmacology studies have revealed that DEPs are associated with processes such as muscle contraction, glycolysis, hemostasis, epigenetic regulation of gene expression, transport of small molecules, neutrophil extracellular trap formation, adrenergic signaling in cardiomyocytes, systemic lupus erythematosus, alcoholism, and platelet activation, signaling, and aggregation. Computational studies revealed strong binding affinities with six proteins associated with cancer, positive pharmacokinetic properties, and no toxicity. Conclusions: Our contribution suggests that IA may be a compound with potential therapeutic effects against NHL. Full article

Background/Objectives: There is a need for prediction models which enable weighing benefits against risks of different treatment strategies for individual Hodgkin lymphoma (HL) patients. Therefore, we aimed to predict absolute risk of progression, first relapse or death (PRD) with and without incorporating HL treatment. Methods: The prognostic and treatment information of 2343 patients treated for classical HL at ages 15–60 years between 2008 and 2018 in the Netherlands was used to predict absolute risk of PRD up to 5 years after diagnosis using Cox proportional hazard models allowing for time-varying coefficients. Models were externally validated in 1675 patients treated for classical HL in Denmark between 2000 and 2018. Results: In early stages, gender, leukocyte, and lymphocyte counts were associated with risk of PRD. Additionally, receiving >4 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or ABVD plus radiotherapy predicted lower risk of relapse compared with receiving ≤4 cycles of ABVD. In advanced stages, age, albumin and leukocyte counts predicted PRD risk. Receiving (escalated) BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) predicted lower PRD risk compared to ABVD. In Danish patients treated between 2008 and 2018, adding treatment information improved 5-year Inverse Probability of Censoring Weighted (IPCW) Area Under the Curve (AUC) values from 0.63 (95% Confidence Interval (CI): 0.55–0.72) to 0.71 (95% CI: 0.63–0.79) in early stages (p-value = 0.04) and from 0.59 (95% CI: 0.52–0.65) to 0.62 (95% CI: 0.55–0.68) in advanced stages (p-value = 0.33). Conclusions: We developed well calibrated models with reasonable discrimination, not only incorporating pre-treatment prognostic factors but also treatment effect enabling the prediction of absolute risk of first relapse/progression. Full article

Primary cutaneous lymphomas (PCLs), including cutaneous T-cell lymphomas (CTCL) and primary cutaneous B-cell lymphomas (PCBCL), are a diverse group of non-Hodgkin lymphomas that primarily affect the skin. Radiotherapy (RT) plays a pivotal role in the treatment of these lymphomas, particularly for localized disease, due to its ability to deliver precise, skin-directed treatment. Mycosis fungoides (MF) and Sézary syndrome (SS), the most common subtypes of CTCL, often require skin-directed therapies such as electron beam therapy and superficial brachytherapy to manage localized lesions. Electron beam therapy, including total skin electron beam therapy (TSEBT), has been utilized for decades, offering high response rates but with the risk of cumulative skin toxicity. Recently, low-dose radiotherapy (LDRT) has gained attention as an effective alternative that reduces toxicity while maintaining durable responses. Superficial brachytherapy is another modality that delivers radiation through custom molds, allowing for homogeneous dosing over complex anatomical areas like the face. Both teleradiotherapy and brachytherapy have demonstrated high complete response rates, with low recurrence rates observed when higher doses are used. In the context of primary cutaneous B-cell lymphomas, such as primary cutaneous marginal zone lymphoma (PCMZL) and primary cutaneous follicle center lymphoma (PCFCL), radiotherapy also offers excellent local control, particularly for indolent subtypes. However, more aggressive subtypes, such as diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), may require systemic therapies in addition to radiation. Overall, teleradiotherapy and brachytherapy are essential components of the therapeutic arsenal for primary cutaneous lymphomas, offering effective disease control with manageable toxicity, while ongoing research focuses on optimizing treatment strategies and exploring novel combinations with systemic therapies. Full article

Epstein-Barr Virus (EBV) is a causative agent of infectious mononucleosis and is strongly associated with Burkitt lymphoma, Hodgkin lymphoma, and nasopharyngeal carcinoma. EBV encodes a deubiquitinating enzyme, BPLF1, which is important for infectious virus production, B-cell immortalization, and tumorigenesis. To elucidate BPLF1’s role, an affinity-based mass spectrometry screen was performed, which suggested that BPLF1 and mTOR interact. mTOR, a critical mediator within cellular signaling cascades and oncogenesis, exists in two distinct complexes: mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2). Here, we show that BPLF1 has direct deubiquitinating (DUB) activity on mTOR, removing both K48- and K63-ubiquitin linkages. Additionally, WT BPLF1 decreased mTORC1 localization to the lysosome and decreased the phosphorylation of mTORC1 downstream effectors, 4E-BP1 and S6K1. BPLF1 also had DUB activity on Raptor and Rictor, which have both been shown to preferentially cause the formation of mTORC2 over mTORC1 when not ubiquitinated. Immunoprecipitation of mTOR shows decreased mTORC1 formation in the presence of WT BPLF1. Importantly, treatment with rapamycin, an mTORC1 inhibitor, increased infectious virus production, while JR-AB2-011, an mTORC2 inhibitor, reduced infectious virus production. Taken together, these data demonstrate that BPLF1’s effect on the mTOR signaling cascade regulates cellular and viral processes during EBV infectivity and replication. Full article

Background/Objectives: Epstein–Barr virus (EBV) detection patterns in lymphoproliferative disorders (LPDs) show significant geographical variation worldwide. Regional epidemiological data are essential for understanding viral distribution patterns and developing appropriate clinical surveillance strategies. This study aimed to determine EBV detection frequency in LPDs using available molecular and immunohistochemical methods in Western Mexico. Methods: We conducted a cross-sectional study of 200 formalin-fixed paraffin-embedded tissue samples from patients diagnosed with LPDs (2015–2019) at Hospital Civil de Guadalajara. EBV detection combined with real-time PCR targeting the BNTp143 gene and immunohistochemistry for LMP-1 protein. Cases were classified following current WHO criteria. Statistical analysis included multivariate logistic regression, diagnostic concordance assessment, and age-stratified analysis. Results: EBV detection frequency reached 35.5% overall, with marked differences between neoplastic (53.9%) and reactive LPDs (24.2%) (OR: 3.515; 95% CI: 1.859–6.645, p < 0.001). Hodgkin lymphoma showed the highest detection rate (80.6%), significantly exceeding non-Hodgkin lymphoma (39.3%) (OR: 6.43; 95% CI: 2.08–19.41, p = 0.001). Age-stratified analysis revealed predominant adult involvement (49.1% vs. 22.0% in young adults, p = 0.025). We identified three epidemiological categories based on detection probability patterns. Conclusions: This study represents the first comprehensive molecular and immunohistochemical characterization of Epstein–Barr virus in lymphoproliferative disorders from Western Mexico, establishing distinct epidemiological patterns that align with Latin American regional characteristics. The validated methodology provides a reproducible framework for multi-center studies, while the epidemiological data serve as an essential baseline for future longitudinal research and resource optimization in similar healthcare settings. Full article

Sweet syndrome (SS) is a rare neutrophilic dermatosis often associated with hematologic malignancies, particularly myelodysplastic syndromes (MDSs). We report a case of SS-like dermatosis in a patient with MDS who subsequently developed peripheral T-cell non-Hodgkin lymphoma (NHL). We review the literature on Sweet syndrome to contextualize this atypical presentation Methods: We present a case report of a 77-year-old male with leukopenia and known MDS, admitted for a persistent, infiltrated erythematous eruption. The patient underwent repeated dermatologic assessments, and serial skin and bone marrow biopsies with histopathologic and immunohistochemical analysis. A literature review was also conducted, focusing on SS in association with hematologic malignancies, including T-cell NHL. Results: Initial skin biopsies were inconclusive, and SS was diagnosed clinically based on lesion morphology and a prompt response to corticosteroids, despite the absence of definitive neutrophilic infiltrates. During follow-up, the patient’s condition progressed with worsening cytopenias and recurrent febrile episodes. Repeat biopsies eventually confirmed the diagnosis of peripheral T-cell NHL with secondary hemophagocytic lymphohistiocytosis (HLH). Conclusions: This case illustrates the diagnostic uncertainty of SS-like eruptions in hematologic patients when histopathological findings are atypical or absent. Corticosteroid responsiveness may guide early diagnosis. Full article

Background/Objectives: Chronic hepatitis C virus (HCV) infection is associated with a wide spectrum of extrahepatic manifestations, involving the immune, dermatologic, endocrine, vascular, and neuropsychiatric systems. Among these, mixed cryoglobulinemic vasculitis (CryoVas) remains one of the most clinically relevant complications. This work aims to provide a structured overview of HCV-related extrahepatic conditions and to analyze the clinical and virological outcomes of direct-acting antivirals (DAAs) in CryoVas patients. Methods: We first categorized and reviewed extrahepatic manifestations of HCV across five major domains: immune, inflammatory/metabolic/vascular, dermatological, thyroid, and neuropsychiatric. Subsequently, we conducted a comparative analysis of five clinical studies evaluating the impact of DAA therapy in patients with CryoVas. Data on demographics, clinical symptoms, treatment regimens, sustained virological response, and clinical response were extracted and summarized. Results: HCV was found to be associated with numerous extrahepatic conditions, including mixed cryoglobulinemia, non-Hodgkin lymphoma, autoimmune thyroiditis, insulin resistance, and neurocognitive symptoms. In the CryoVas subgroup analysis, virological response rates were uniformly high (88.9–100%), but clinical remission varied significantly. Complete response ranged from 39% to 90%, highlighting a discrepancy between viral eradication and extrahepatic symptom resolution. These findings underscore the need for individualized follow-up and further investigation into persistent immunological dysfunction post-sustained virological response (SVR). However, clinical outcomes were more variable: complete response (CR) varied between 39% and 90%, partial response (PR) ranged from 4% to 42%, and no response (NR) was reported in 0% to 40% of cases. Although significant improvement in key manifestations such as purpura, arthralgia, and neuropathy was frequently observed, a subset of patients continued to exhibit residual or refractory symptoms despite achieving SVR. Conclusions: HCV infection exerts multisystemic effects that extend beyond liver pathology. While DAAs offer near-universal virological clearance, the heterogeneous clinical response in CryoVas underscores the need for closer monitoring of extrahepatic outcomes. Future research should assess whether combining DAAs with immunomodulatory strategies can improve symptom control and long-term outcomes in patients with severe or refractory CryoVas. Full article

Hodgkin’s Lymphoma (HL) affects approximately 8500 individuals annually in the United States. The 5-year relative survival rate has improved to 88.5%, driven by transformative advances in immunotherapy and precision oncology. The integration of Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) has redefined treatment paradigms. The phase III SWOG S1826 trial established nivolumab plus doxorubicin, vinblastine, and dacarbazine (N + AVD) as an emerging new standard for advanced-stage HL, achieving a 2-year progression-free survival (PFS) of 92% compared to 83% for BV plus AVD (HR 0.48, 95% CI: 0.33–0.70), with superior safety, particularly in patients over 60. In relapsed/refractory HL, pembrolizumab outperforms BV, with a median PFS of 13.2 versus 8.3 months (HR 0.65, 95% CI: 0.48–0.88), as demonstrated in the KEYNOTE-204 trial. Emerging strategies, including novel ICI combinations, minimal residual disease (MRD) monitoring via circulating tumor DNA (ctDNA), and artificial intelligence (AI)-driven diagnostics, promise to further personalize therapy. This review synthesizes HL’s epidemiology, pathogenesis, diagnostic innovations, and therapeutic advances, highlighting the role of precision medicine in addressing unmet needs and disparities in HL care. Full article

Background/Objectives: Aberrant expression of high-mobility group protein B1 (HMGB1) has been linked to cancer development and progression. Methods: To better comprehend the role of HMGB1 expression in cancer, a tissue microarray containing 14,966 samples from 134 different tumor entities and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Results: Strong HMGB1 staining occurred in almost all normal cell types and in most cancers. Of 11,808 evaluable cancers, only 7.8% showed complete absence of HMGB1 staining (HMGB1 deficiency) while 9.9% showed 1+, 25.0% showed 2+, and 57.2% showed 3+ HMGB1 positivity. Absence of HMGB1 staining mostly occurred in pheochromocytoma (90.0%), seminoma (72.4%), gastrointestinal stromal tumor (28.6%), adrenal cortical carcinoma (25.0%), and Hodgkin’s lymphoma (25.0%). Low HMGB1 staining was linked to poor histologic grade (p < 0.0001), advanced pT stage (p < 0.0001), high UICC stage (p < 0.0001), and distant metastasis (p = 0.0413) in clear cell renal cell carcinoma, invasive tumor growth in urothelial carcinoma (pTa vs. pT2–4, p < 0.0001), mismatch repair deficiency (p = 0.0167) in colorectal cancers, and advanced pT stage in invasive breast carcinoma of no special type (p = 0.0038). Strong HMGB1 staining was linked to nodal metastases in high-grade serous ovarian carcinomas (p = 0.0213) and colorectal adenocarcinomas (p = 0.0137), as well as to poor histological grade in squamous cell carcinomas (p = 0.0010). Conclusions: HMGB1 deficiency and reduced HMGB1 expression occur in a broad range of different tumor entities. Low rather than strong HMGB1 staining is often linked to an aggressive tumor phenotype. Whether HMGB1 deficiency renders cells susceptible to specific drugs remains to be determined. Full article

T-cell-engaging antibodies are a promising new type of treatment for patients with refractory or relapsed (R/R) diffuse large B-cell lymphoma, which has changed the prognosis and evolution of these patients in clinical trials. Bispecific antibodies (BsAbs) bind to two different targets (B and T lymphocytes) at the same time and in this way mimic the action of CAR (chimeric antigen receptor) T-cells. They are the T-cell-engaging antibodies most used in practice and are a solution for patients who do not respond to second- or later-line therapies, including chemoimmunotherapy, followed by salvage chemotherapy and hematopoietic stem cell transplantation. They are a therapeutic option for patients who are ineligible for CAR T-cell therapy and are also active in those with prior exposure to CAR T-cell treatment. A remarkable advantage of BsAbs is their rapid availability, even if the disease progresses rapidly, unlike CAR T-cell treatment, and they avoid the practical and financial challenges raised by autologous CAR T-cell therapies. CAR-T has been proven to have better efficacy compared to BsAbs, but cytokine release syndrome and neurotoxicity have appeared significantly more frequently in patients treated with CAR T-cells. The possibility of combining BsAbs with chemotherapy and their administration for relapses or as a frontline therapy is being studied to increase their efficacy. BsAbs are a life-saving therapy for many patients with diffuse large B-cell malignant non-Hodgkin’s lymphoma (NHL) who have a poor prognosis with classical therapies, but are not without adverse effects and require careful monitoring. Full article

Background/Objectives: Diffuse Large B-Cell Lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and demands precise segmentation and classification of nuclei for effective diagnosis and disease severity assessment. This study aims to evaluate the performance of HoVerNet, a deep learning model, for nuclei segmentation and classification in CMYC-stained whole slide images and to assess its integration into a user-friendly diagnostic tool. Methods: A dataset of 122 CMYC-stained whole slide images (WSIs) was used. Pre-processing steps, including stain normalization and patch extraction, were applied to improve input consistency. HoVerNet, a multi-branch neural network, was used for both nuclei segmentation and classification, particularly focusing on its ability to manage overlapping nuclei and complex morphological variations. Model performance was validated using metrics such as accuracy, precision, recall, and F1 score. Additionally, a graphic user interface (GUI) was developed to incorporate automated segmentation, cell counting, and severity assessment functionalities. Results: HoVerNet achieved a validation accuracy of 82.5%, with a precision of 85.3%, recall of 82.6%, and an F1 score of 83.9%. The model showed powerful performance in differentiating overlapping and morphologically complex nuclei. The developed GUI enabled real-time visualization and diagnostic support, enhancing the efficiency and usability of DLBCL histopathological analysis. Conclusions: HoVerNet, combined with an integrated GUI, presents a promising approach for streamlining DLBCL diagnostics through accurate segmentation and real-time visualization. Future work will focus on incorporating Vision Transformers and additional staining protocols to improve generalizability and clinical utility. Full article

Classical Hodgkin lymphoma (cHL) is a biologically and clinically unique malignancy characterized by rare Hodgkin and Reed–Sternberg (HRS) cells surrounded by a dense and diverse inflammatory infiltrate. These malignant cells actively reshape the tumor microenvironment (TME) through metabolic reprogramming and immune evasion strategies. This review synthesizes current knowledge on how metabolic alterations contribute to tumor survival, immune dysfunction, and therapeutic resistance in cHL. We discuss novel therapeutic approaches aimed at disrupting these processes and examine the potential of combining metabolic interventions with immune-based strategies—such as immune checkpoint inhibitors (CPIs), epigenetic modulators, bispecific antibodies, and CAR-T/CAR-NK cell therapies—which may help overcome resistance and enhance anti-tumor responses. Several agents are currently under investigation for their ability to modulate immune cell metabolism and restore effective immune surveillance. Altogether, targeting metabolic vulnerabilities within both tumor and immune compartments offers a promising, multifaceted strategy to improve clinical outcomes in patients with relapsed or refractory cHL. Full article

Background and Objectives: Metabolic tumor volume (MTV) and inflammation-based indices have recently gained attention as potential prognostic markers of diffuse large B-cell lymphoma (DLBCL). We aimed to evaluate the prognostic significance of metabolic and systemic inflammatory parameters in predicting treatment response, relapse, and overall survival (OS) in patients with DLBCL. Materials and Methods: This retrospective cohort study included 70 patients with DLBCL. Clinical characteristics, laboratory values, and metabolic parameters, including maximum standardized uptake value (SUVmax^liver and SUVmax), heterogeneity indices HI1 and HI2, and MTV were analyzed. Survival outcomes were assessed using Kaplan–Meier and log-rank tests. Receiver operating characteristic analyses helped evaluate the diagnostic performance of the selected biomarkers in predicting relapse and mortality. Univariate and multivariate logistic regression analyses were conducted to identify the independent predictors. Results: The mean OS and mean relapse-free survival (RFS) were 71.6 ± 7.4 and 38.7 ± 2.9 months, respectively. SUVmax^liver ≤ 22 and HI2 > 62.3 were associated with a significantly shorter OS. High lactate dehydrogenase (LDH) levels and HI2 > 87.9 were significantly associated with a reduced RFS. LDH, SUVmax^liver, and HI2 had a significant predictive value for relapse. SUVmax^liver and HI2 levels were also predictive of mortality; SUVmax^liver ≤ 22 and HI2 > 62.3 independently predicted mortality, while HI2 > 87.9 independently predicted relapse. MTV was not significantly associated with survival. Conclusions: Metabolic tumor burden and inflammation-based markers, particularly SUVmax^liver and HI2, are significant prognostic indicators of DLBCL and may enhance risk stratification and aid in identifying patients with an increased risk of relapse or mortality, potentially guiding personalized therapy. Full article