Search Results (230)

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

Relapsed/refractory diffuse large B-cell lymphoma and other non-Hodgkin lymphomas represent significant clinical challenges, particularly in patients who have exhausted standard immunochemotherapy and cellular therapies. Bispecific antibodies and antibody–drug conjugates have emerged as promising treatments, offering targeted and more effective treatment options compared to current standards. Bispecific antibodies, including epcoritamab and glofitamab, third-line therapies for diffuse large B-cell lymphoma, are recombinant immunoglobulins engineered to recognize two distinct antigens or epitopes simultaneously. This capability enhances therapeutic precision by bridging immune effector cells and tumor cells and modulating multiple signaling pathways involved in the pathogenesis of non-Hodgkin lymphoma. In the context of new therapies, antibody–drug conjugates, such as loncastuximab tesirine, are therapies composed of monoclonal antibodies linked to cytotoxic agents, in which the antibody selectively binds to tumor-associated antigens, delivering the cytotoxic payload directly to cancer cells while minimizing off-target effects. They combine the specificity of antibodies with the potency of chemotherapy, offering enhanced efficacy and safety in hematological malignancies. Ongoing clinical trials are investigating other molecules like odronextamab and the use of bispecific antibodies in combination regimens and earlier lines of therapy. The aim of this review is to explore actual therapies in relapsed/refractory diffuse large B-cell lymphoma, focusing on bispecific antibodies and antibody–drug conjugates. Full article

Intravascular lymphoma (IVL) is a rare, aggressive subtype of non-Hodgkin lymphoma (NHL) characterized by the selective proliferation of neoplastic lymphoid cells within small and medium-sized blood vessels, most frequently of B-cell origin (IVLBCL). Its protean clinical presentation, lack of pathognomonic findings, and absence of tumor masses or lymphadenopathies often lead to diagnostic delays and poor outcomes. IVLBCL can manifest in classic, hemophagocytic syndrome-associated (HPS), or cutaneous variants, with extremely variable organ involvement including the central nervous system (CNS), skin, lungs, and endocrine system. Diagnosis requires histopathologic identification of neoplastic intravascular lymphoid cells via targeted or random tissue biopsies. Tumor cells are highly atypical and display a non-GCB B-cell phenotype, often expressing CD20, MUM1, BCL2, and MYC; molecularly, they frequently harbor mutations in MYD88 and CD79B, defining a molecular profile shared with ABC-type DLBCL of immune-privileged sites. Therapeutic approaches are based on rituximab-containing chemotherapy regimens (R-CHOP), often supplemented with CNS-directed therapy due to the disease’s marked neurotropism. Emerging strategies include autologous stem cell transplantation (ASCT) and novel immunotherapeutic approaches, potentially exploiting the frequent expression of PD-L1 by tumor cells. A distinct but related entity, intravascular NK/T-cell lymphoma (IVNKTCL), is an exceedingly rare EBV-associated lymphoma, showing unique own histologic, immunophenotypic, and molecular features and an even poorer outcome. This review provides a comprehensive overview of the current understandings about clinicopathological, molecular, and therapeutic landscape of IVL, emphasizing the need for increased clinical awareness, standardized diagnostic protocols, and individualized treatment strategies for this aggressive yet intriguing malignancy. Full article

Background/Objectives: Reprogramming of the cellular metabolism is a hallmark of cancer, offering therapeutic opportunities to target cancer cell vulnerabilities for therapeutic purposes. 3-Bromopyruvate (3BP) is a small alkylating agent that functions as an anti-metabolite, targeting key substrates in cancer metabolism and demonstrating antitumor activity across multiple cancer types. However, unformulated 3BP is associated with significant toxicity. This study investigates the efficacy of KAT/3BP, a clinical derivative of 3BP currently in phase 1 trials for hepatocellular carcinoma, in preclinical lymphoma models. Results: In vitro, KAT/3BP exhibited cytotoxic activity across 12 lymphoma cell lines—including diffuse large B-cell lymphoma and mantle cell lymphoma—with a median IC₅₀ of 3.7 μM. It also remained effective against lymphoma cell lines with acquired resistance to FDA-approved therapies. In vivo, treatment with KAT/3BP led to reduced tumor size in a syngeneic mouse model, with the combination of oral and intratumoral administration showing the greatest efficacy. Furthermore, KAT/3BP demonstrated synergistic activity when combined with standard lymphoma therapies such as bendamustine and R-CHOP. Conclusions: Our findings highlight the potential of KAT/3BP as a novel therapeutic option, either as a single agent or in combination regimens, for treating lymphomas. Full article

Thrombosis is a common complication in cancer patients, with a substantial impact on morbidity and mortality. Diffuse large B-cell lymphoma (DLBCL) and other aggressive lymphomas carry a high venous thromboembolism (VTE) risk. Extracellular vesicles (EVs) have gained attention in recent research as a new potential biomarker for VTE development. To determine the profile and association of EVs with VTE in patients with DLBCL, we conducted a prospective cohort study on 62 patients diagnosed with DLBCL. A total of 11 patients (17.7%) developed VTE. The concentrations of platelet-derived EVs (PEVs), E-selectin+ EVs, P-selectin+ EVs, tissue factor (TF)-positive/CD20+ EVs, TF−/CD19+ EVs, TF−/CD45+ EVs, and TF−/CD20+ EVs were significantly higher in DLBCL patients compared to healthy controls. In contrast, the concentration of TF− PEVs was significantly lower in DLBCL patients compared to healthy controls. No statistically significant differences were observed in the concentrations of the EV profiles among the DLBCL patients with and without VTE. Using Cox regression analysis, we found that none of the observed EV populations demonstrated an association with overall survival (OS). In conclusion, patients with DLBCL have elevated concentrations of distinct EV populations—in particular, PEVs, E-selectin EVs, P-selectin EVs, TF+/CD20+ EVs, and TF− DLBCL/B-cell EVs (CD19, CD20, CD45)—compared to healthy controls. DLBCL patients exhibit a specific EV profile, which is not significantly related to the risk of VTE and OS outcomes. Our data provide an intriguing insight into EV profiles in patients with DLBCL. Additional research is needed to elucidate these findings further. Full article

Background: Diffuse large B-cell lymphomas (DLBCLs) are the most common, aggressive disease form that accounts for 30% of all lymphoma cases. Identifying patients who will respond to these advanced cell-based therapies is an unaddressed challenge. Methods: We propose to develop a radiomics- (quantitative image metric) based signature on the patients’ imaging scans (positron emission tomography/computed tomography, PET/CT) and use these metrics to prognosticate response to axi-cel (axicabtagene ciloleucel), autologous CD19 chimeric antigen receptor (CAR) T-cell (CAR-T) therapy. We curated a cohort of 155 patients with relapsed/refractory (R/R) DLBCL who were treated with axi-cel. Using their baseline image scan (PET/CT), the largest lesions related to nodal/extra-nodal disease were identified and characterized using imaging metrics (radiomics). We used principal component (PC) analysis to reduce the dimensionality of these features across the functional categories (size, shape, and texture). We evaluated the prognostic ability of radiomic-based PC to treatment response (1-year), measured by overall survival (OS) and progression-free survival (PFS). Results: We found that radiomic PC was prognostic of overall survival (Shape-PC, q < 0.013/0.0108, Size-PC, q < 0.003/0.0088), in CT/PET, respectively. In comparison, the metabolic tumor volume (MTV) was prognostic (q < 0.0002/0.0007). The radiomic PCs across the functional categories showed moderate to weak correlation with MTV, Spearman’s ρ of 0.44/0.35/0.27, and 0.45/0.36/0.55 for Size/Shape/Texture-PC1 obtained on PET and CT, respectively. Conclusions: We found radiomic PC based on size and shape metrics that are able to prognosticate treatment response to CAR-T therapy. Full article

Liquid biopsy through the analysis of circulating tumor DNA (ctDNA) is emerging as a powerful and non-invasive tool complementing tissue biopsy in lymphoma management. Whilst tissue biopsy remains the diagnostic gold standard, it fails to detect the molecular heterogeneity of the tumor’s multiple compartments and poses challenges for sequential disease monitoring. In diffuse large-B-cell lymphoma (DLBCL), ctDNA facilitates non-invasive genotyping by identifying hallmark mutations (e.g., MYD88, CD79B, EZH2), enabling molecular cluster classification. Dynamic changes in ctDNA levels during DLBCL treatment correlate strongly with progression-free survival and overall survival, underscoring its value as a predictive and prognostic biomarker. In Hodgkin’s lymphoma, characterized by a scarcity of malignant cells in tissue biopsies, ctDNA provides reliable molecular insights into tumor biology, response to therapy, and relapse risk. In primary central nervous system lymphoma, the detection of MYD88 L265P in ctDNA offers a highly sensitive, specific, and minimally invasive diagnostic option. Likewise, in aggressive T-cell lymphomas, ctDNA supports molecular profiling, aligns with tumor burden, and shows high concordance with tissue-based results. Ongoing and future clinical trials will be critical for validating and standardizing ctDNA applications, ultimately integrating liquid biopsy into routine clinical practice and enabling more personalized and dynamic lymphoma care. Full article

Primary cutaneous lymphomas (PCLs) constitute a heterogeneous group of rare diseases. Previously, few studies have focused on the aspect of scalp involvement by PCLs. The objective of this study was to analyze the clinical presentation, diagnostic pathways, and treatment methods in patients diagnosed with scalp PCLs. A comprehensive literature review was conducted using the PubMed database, with the search terms “scalp” AND “cutaneous lymphoma”, “folliculotropic mycosis fungoides” AND “scalp”, “trichoscopy” AND “lymphoma”, and “dermoscopy” AND “scalp” AND “lymphoma.” The search was limited to articles published from database inception to May 2, 2024. Based on the title and abstract analysis, we included articles on PCLs involving the scalp. After a thorough review of the full manuscripts, several were excluded due to irrelevance, the absence of essential clinical data, discrepancies in patient age, gender, and diagnosis, and a lack of information pertinent to scalp PCLs. The literature search identified 1482 patients with scalp involvement in PCLs. Of the total number of cases, 1096 were diagnosed with B-cell PCLs, 384 with T-cell PCLs, and two cases lacked a precise PCL diagnosis. Primary cutaneous follicle center lymphoma was the most frequently reported B-cell PCL of the scalp, while mycosis fungoides was the most common T-cell PCL. Alopecia was observed in 69.0% of the patients analyzed, with the most prevalent form being non-scarring focal alopecia. It is imperative to consider the scalp in patients with PCLs, particularly in light of the knowledge that some lymphomas affecting the scalp exhibit a higher degree of aggressiveness. Full article

Background: Primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS), is a rare and aggressive form of lymphoma. Its characteristics and treatment outcomes remain poorly understood. Methods: We identified 15 patients who were diagnosed with pcPTCL-NOS between January 2014 and August 2024 at Tianjin Medical University Cancer Institute and Hospital (TMUCIH) in this retrospective study. The clinical and immunophenotypic features, treatment regimens, and outcomes of these patients were investigated. Results: All patients (4 men, 11 women; median age 54 years) presented with skin lesions, including five stage T1, four stage T2 and six stage T3 lesions. pcPTCL-NOS manifests clinically either with solitary or disseminated rapidly growing nodules/tumors and papules and, less often, ulcers. The lesion sites in patients presenting with solitary/localized tumors (stage T1 and T2) were the head and limbs, and those in patients presenting with disseminated lesions (stage T3) were the trunk, head, and limbs. The CD4/CD8 immunophenotypic characteristics were as follows: CD4+/CD8− 53.33%; CD4+/CD8+ 26.67%; CD4−/CD8− 13.33%; and CD4−/CD8+ 6.67%. One patient had a T follicular helper (TFH) phenotype. Five patients had aberrant expression of the B-cell marker CD20 by tumor cells. All patients received CHOP or CHOP-like regimens as the initial treatment, with three patients undergoing complete lesion resection before chemotherapy, seven patients receiving treatment combined with chidamide (tucidinostat), two patients receiving treatment combined with brentuximab vedotin, two patients receiving treatment combined with mitoxantrone liposomes (Lipo-Mit), three patients receiving treatment combined with radiotherapy, and two patients receiving ASCT after the first-line treatment. The OS rates at 1 year, 2 years, and 3 years were 80%, 77.8%, and 77.8%, respectively; the PFS rates were 60%, 44.4%, and 33.3%, respectively. With a median follow-up of 40 months, the median PFS was 21 months, and the median OS was not reached. Univariate analyses revealed that patients with B symptoms and the CD4−/CD8− phenotype had inferior outcomes (p < 0.05). Age, sex, tumor stage, PIT score, Ki-67 index, elevated β2-MG levels, expression of CD20 or PD1, and treatment selection were not associated with the prognosis. A trend of a survival benefit in patients with solitary (T1) tumors compared with patients with disseminated (T2, T3) tumors was observed, suggesting that it is possible to reduce the intensity of treatment in patients with T1 tumors in the future. Conclusions: pcPTCL-NOS is an aggressive but poorly characterized lymphoma that may require early and active systemic treatment. However, for patients with T1 tumors, reducing the intensity of treatment with CHOP should be appropriately considered. Full article

Diffuse large B-cell lymphoma (DLBCL), recognized as the most prevalent variant of adult non-Hodgkin lymphoma, presents considerable challenges in diagnosis owing to its diverse morphological features and frequent extranodal involvement, which may frequently mimic nonhematopoietic neoplasms. The 2022 WHO Classification of Lymphoid and Hematopoietic Tissues provides essential updates, highlighting the necessity of combining morphology, immunohistochemistry, cytogenetics, and molecular testing for precise subclassification. This review presents a practical method for differentiating DLBCL from other aggressive B-cell neoplasms, such as Burkitt lymphoma, B-lymphoblastic lymphoma, and mantle cell lymphoma. It highlights vital diagnostic tools, including CD45, B/T-cell markers, germinal center markers, and the Hans algorithm, as well as the role of FISH in identifying rearrangements of key genes MYC, BCL2, and BCL6, which are significant for recognizing double-hit and triple-hit lymphomas. Special focus is given to EBV-associated DLBCL and uncommon subtypes featuring plasmablastic or ALK-positive traits. This review aims to enhance diagnostic accuracy and ensure appropriate treatment strategies for patients with large B-cell lymphomas by emphasizing thorough morphological evaluation, specific adjunct testing, and adherence to the most recent classification standards. Full article

With the advent of new therapeutic approaches, there is hope that anticancer treatment will eventually be possible without the use of chemotherapy. Efficient immunotherapeutic options have recently emerged in many cancers, offering a less aggressive approach, with overall better tolerance, making them also suitable for frail patients. Response to immunotherapy relies on the availability, functionality, and efficacy of the host’s immune effector mechanisms. One of the key factors determining the efficacy of immunotherapy is the tumor microenvironment, which encompasses various immune effectors, including macrophages, which play a crucial role in regulating immune responses through phagocytosis and antigen presentation. Macrophages are prototypically divided, according to their polarization, into either the pro-inflammatory M1 type or the anti-inflammatory M2 type. In the tumor microenvironment, M2-polarized macrophages, known as tumor-associated macrophages (TAMs), are the predominant phenotype and are associated with tumor progression. The M1/M2 paradigm contributes to the understanding of tumor progression. Due to the variable microenvironment, the mechanisms regulating TAMs can vary across different cancers. Variations in TAM polarization may account for the different treatment responses in patients with similar diseases. This paper investigates the connection between TAMs, disease progression, and treatment responses in the most frequent solid hematologic cancer, diffuse large B-cell lymphoma. Full article

Primary mediastinal large B-cell lymphoma (PMLBCL) is a rare and aggressive non-Hodgkin lymphoma (NHL), considered a specific entity with proper characteristics, therapies, and prognosis. First-line treatment is not unique, and subsequent strategies in case of disease persistence or relapse are the subject of debate and studies. In this scenario, [18F]FDG PET/CT plays a pivotal role both in characterizing the mediastinal mass, the main feature of PMLBCL, in staging, in restaging during therapy (interim PET), and at the end of treatment (EoT PET), to guide clinical management and give prognostic insights. The main issue with PMLBCL is distinguishing viable disease from residual fibrotic/inflammatory mass after therapy and, consequently, settling the next clinical strategy. Novel therapeutic approaches are ongoing and associated with the deepening of [18F]FDG PET/CT potentials as a principal tool in this context. In this review, we will explore PMLBCL from a Nuclear Medicine point of view to help clinicians in the management of these patients. Full article

Waldenström Macroglobulinemia (WM) is a rare, indolent B-cell lymphoproliferative disorder characterized by the production of monoclonal IgM paraprotein and infiltration of the bone marrow by lymphoplasmacytic cells. While WM generally exhibits a slow clinical course, it has the potential to progress into more aggressive hematologic malignancies, such as diffuse large B-cell lymphoma. The TP53 gene, often referred to as the “guardian of the genome”, plays a pivotal role in maintaining genomic stability, regulating the cell cycle, and orchestrating apoptosis. Mutations in TP53 undermine these essential processes, resulting in dysregulated cellular proliferation, defective apoptotic mechanisms, and genomic instability—hallmarks of cancer development. Although TP53 mutations have been extensively investigated in several hematologic malignancies, including acute myeloid leukemia, myelodysplastic syndromes, and chronic lymphocytic leukemia, their role in WM remains underexplored. Emerging evidence suggests that TP53 mutations may have a significant impact on the disease progression and therapeutic response in WM. This review examines the current knowledge of TP53 mutations in WM, highlighting their implications for prognosis and therapeutic strategies. A deeper understanding of the role of TP53 in WM could provide critical insights for improving disease management and advancing the development of targeted therapies. Full article