Search Results (34)

Numerous studies point to the significance of cathepsin B (CTSB) in the development of carcinoma. Therefore, the aim of this pilot study was to investigate the levels of cathepsin B (CTSB) and the expression of CTSB mRNA in the plasma of non-Hodgkin lymphoma (NHL) patients. Methods: The study included 44 newly diagnosed NHL patients and 35 healthy volunteers comprising the control group. CTSB in the plasma samples were detected using the enzyme-linked immunosorbent assay (ELISA). Results: The level of CTSB was significantly higher in NHL patients compared to control subjects: 15.28 (11.68–17.23) versus 11.57 (10.12–13.41), p = 0.003. In addition, a positive correlation between plasma CTSB mRNA and CTSB after therapy was observed (rho = 0.591, p = 0.026). Regarding redox parameters, we found a negative correlation between CTSB and the total antioxidant status (TAS) (rho = −0.499, p = 0.035), as well as a positive correlation with the total oxidant status (TOS) (rho = 0.576, p = 0.012). Conclusions: Targeting CTSB might have significant clinical relevance in the diagnostics of NHL. Full article

Background/Objectives: Classic Hodgkin lymphoma (cHL) is a predominantly curable B-cell malignancy. However, primary refractory and relapsed (R/R) cHL remain therapeutic challenges, especially in regions with high tuberculosis (TB) prevalence, where clinical and radiologic features overlap and can obscure the correct diagnosis. This article, presenting a case of R/R cHL mimicking disseminated TB, reviews the evolving paradigm in R/R cHL management. Methods: A 30-year-old Middle Eastern male with advanced nodular sclerosis cHL initially achieved a complete remission (CR) with escalated BEACOPP chemotherapy. Shortly afterward, he developed respiratory symptoms and diffuse miliary pulmonary nodules, highly suggestive of disseminated TB. Despite extensive negative TB workup, including QuantiFERON-TB Gold testing, sputum acid-fast bacilli (AFB) staining, and PCR, his imaging raised concern for recurrent cHL. Due to the small size and diffuse distribution of nodules, biopsy was unfeasible, prompting empiric salvage therapy with DEHAP-Carbo, brentuximab vedotin (BV), and nivolumab. Results: The rapid and robust metabolic response on PET/CT supported lymphoma relapse rather than TB. Following four cycles of this combined regimen, he proceeded to autologous stem cell transplantation and achieved a second CR. Conclusions: This case highlights the diagnostic difficulties in differentiating cHL relapse from TB in endemic regions, emphasizes the critical role of PET/CT in guiding therapy when histopathological confirmation is impractical, and illustrates the impact of novel immunotherapies in improving outcomes. By underscoring the importance of early diagnostic suspicion and multimodal assessment, this article also reviews the evolving paradigm in R/R cHL management, where personalized approaches and targeted agents increasingly complement or replace traditional chemotherapy regimens. Full article

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common diagnosed aggressive B-cell lymphoma, with poor outcomes in those who experience relapsed or refractory (R/R) disease. Landmark clinical trials have demonstrated the efficacy and safety of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for patients with R/R DLBCL, though further exploration of real-world outcomes (RWOs) and safety data is warranted. Methods: A retrospective chart review was performed to collect patient and disease characteristics from patients with R/R DLBCL receiving CAR T-cell therapy for third-line treatment or beyond at the John Theurer Cancer Center as the standard of care. Results: We report on 82 patients with R/R DLBCL that successfully completed an infusion of an anti-CD19 CAR T-cell product at our institution. Best overall and complete response rates were 74.4% (95% CI, 64.9 to 83.8) and 67.1% (95% CI, 56.9 to 77.2), respectively. From the time of CAR T-cell infusion, median PFS was 26.5 months (95% CI, 8.6 months could not be estimated) and OS was not reached. Subgroup analyses revealed no statistical differences in outcomes by use of bridging therapy, Karnofsky performance status, transformed DLBCL status, and the type of CAR T-cell product used for this study. CAR T-cell therapy was well tolerated, with 58 patients (70.7%) experiencing cytokine-release syndrome and 17 patients (20.7%) experiencing immune effector cell-associated neurotoxicity syndrome. Conclusions: These results of RWOs in third-line patients with R/R DLBCL receiving anti-CD19 CAR T-cell therapy are comparable or superior to prior clinical trials and studies of RWOs, validating the strong efficacy and manageable toxicities of CAR T-cell therapy. Full article

The clinicopathologic spectrum of nodular lymphocyte-predominant Hodgkin lymphoma, now termed “nodular lymphocyte-predominant B-cell lymphoma” (NLPBCL), may include incipient, typical and transformed forms. On the basis of its clinicopathologic spectrum, NLPBCL is very similar to follicular lymphoma not associated with BCL2 translocation. In addition, NLPBCL, based on biopathologic features (gene profiling signature, and phenotypic and morphotypic characteristics), is a germinal center-derived B-cell neoplasm; therefore, it could be included in the follicular lymphoma group of non-Hodgkin lymphoma. Full article

Background: High-grade B-cell lymphoma with c-MYC and BCL2 and/or BCL6 rearrangements (HGBL-DHL/THL) is a recently identified category in the most recent World Health Organization (WHO) classification. For all tumors displaying the appearance of diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL), it is necessary to perform fluorescence in situ hybridization (FISH) in order to achieve an accurate diagnosis. The findings of FISH and immunohistochemistry (IHC) examinations from 50 DLBCL/HGBL samples obtained from Hassan II University Hospital in Fez/Morocco are reported. Methods: This retrospective study included 50 patients diagnosed with DLBCL/HGBL over a period of nine years (2013–2022) and treated with RCHOP chemotherapy protocol. All patients underwent a histological study followed by an immunohistochemical study to confirm the diagnosis and to classify patients according to cell of origin into non-GCB and GCB subtypes; then, a cytogenetic study using FISH was performed to classify patients according to the presence or absence of rearrangements in the c-MYC, BCL2 and BCL6 genes. A comparison was made between the molecular subtypes of DLBCL/HGBL in relation to clinicopathological features and outcomes. Results: Among the 50 cases studied in our population, we found 5 cases of HGBL with DLBCL morphology and 45 cases of DLBCL, which consisted of 13 cases (28.89%) of GCB subtype and 32 cases (71.11%) of non-GCB subtype based on the immunohistochemistry Hans algorithm. After FISH testing of all cases, we found three cases of double-hit lymphoma (DHL) and one case of triple-hit lymphoma (THL). Thus, HGBL-DHL/THL accounted for 8% of the cases. Furthermore, two cases were detected with only one rearrangement in the BCL2 gene and one case harboring a rearrangement in the BCL6 gene. DHL and THL patients and patients with a single rearrangement (BCL2 or BCL6) have a worse prognosis than patients with no rearrangement. Conclusions: DHL and THL are an aggressive entity of HGBL with poorer outcomes in comparison to DLBCL/HGBL NOS. First-line treatment with the RCHOP chemotherapy protocol may not be effective for all aggressive DLBCL cases. More targeted treatment is crucial for better patient outcomes. Full article

Introduction: Primary bone lymphoma (PBL) is a rare clinical entity, accounting for less than 5% of all extranodal non-Hodgkin lymphomas and approximately 5% of primary bone tumors. Diffuse large B-cell lymphoma (DLBCL) is the most common histotype, accounting for about 80% of all PBL cases. Conversely, the incidence of indolent primary bone lymphomas (iPBL) represents less than 1% of all reported PBL cases, and data on these rarer lymphomas are scarce. Drawing on diagnostic criteria developed by the World Health Organization (WHO) and the International Extranodal Lymphoma Study Group (IELSG), we report a rare case of primary bone follicular lymphoma, focusing specifically on the clinical presentation and treatment. Discussion: Additionally, we provide a systematic review of the literature data on this very rare lymphoproliferative entity. Full article

A two-day meeting on controversial topics in hematopathology was held in Bologna, Italy, on 19–20 January 2024. The meeting primarily targeted pathologists lacking experience in hematological neoplasms and pathologists in training. The course aimed to highlight practical diagnostic challenges faced by pathologists and discuss solutions through the application of conventional histology, along with appropriate immunohistological, genetic, and molecular findings. The teaching program included lectures and slide seminars presented by a team of expert hematopathologists who were co-authors of the WHO classification of hematolymphoid tumors. Special interest revolved around “lymphadenitis and lymphoma mimickers”, “a rational approach to low-grade B-cell lymphomas”, and “advancements in defining Hodgkin lymphoma”. A key aspect emphasized by the faculty team was the use of the fifth edition of the WHO Bluebook and the International Consensus Classification (ICC 2022) of lymphomas. Full article

Classic Hodgkin lymphoma (cHL) is a B-cell lymphoma in which tumour cells, the so-called Hodgkin Reed–Sternberg (HRS) cells, are admixed with non-malignant cell types that are a functional part of the disease. Immune cells, fibroblasts, specialised mesenchymal cells, and microvasculature together make up the tumour microenvironment and have functional interactions with tumour cells. HRS cells are surrounded by T and B cells admixed with plasma cells, macrophages, eosinophils, and mast cells. A cross-talk occurs between HRS cells and immune cells of the TME. This cross-talk is mediated either by a large network of cytokines and chemokines expressed by HRS cells or molecules produced by different cell types of the TME, i.e., CD30/CD30L, CD40/CD40L, OX40L/OX40, Il- 3/Il-3R, CCR5/CCL5, CD74 macrophage migration inhibitory factor/macrophages, and PD-L1/PD-1. The over-expression of CD30 and CD40, members of the TNF receptor family, is a hallmark of HRS cells. This review highlights the current development of newer therapeutic strategies as a means of immune checkpoint blockade and suggests that further research should explore innovative molecules aimed at targeting components of HL that are involved in cancer cell growth and/or immune escape. Hopefully, this will influence sensitivity or resistance to checkpoint inhibitor therapy in an individual patient. Full article

The World Health Organization (WHO) “Classification of Tumours of Haematopoietic and Lymphoid Tissues”, published in 2001 and subsequently updated in 2008 and 2017, defined disease entities based on morphologic and phenotypic characteristics, clinical features, and genomic findings. Recently, the criteria for the diagnosis of many lymphoma entities have been refined in a proposal by the International Consensus Classification (ICC). Some provisional categories have now been recognized as “definite” entities, while other categories have undergone major revision. This article reports on the major revisions in the criteria and definition of B- and T-/NK-cell lymphomas by the ICC system. Full article

Background: Artificial intelligence in medicine is a field that is rapidly evolving. Machine learning and deep learning are used to improve disease identification and diagnosis, personalize disease treatment, analyze medical images, evaluate clinical trials, and speed drug development. Methods: First, relevant aspects of AI are revised in a comprehensive manner, including the classification of hematopoietic neoplasms, types of AI, applications in medicine and hematological neoplasia, generative pre-trained transformers (GPTs), and the architecture and interpretation of feedforward neural net-works (multilayer perceptron). Second, a series of 233 diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab-CHOP from the Lymphoma/Leukemia Molecular Profiling Project (LLMPP) was analyzed. Results: Using conventional statistics, the high expression of MYC and BCL2 was associated with poor survival, but high BCL6 was associated with a favorable overall survival of the patients. Then, a neural network predicted MYC, BCL2, and BCL6 with high accuracy using a pan-cancer panel of 758 genes of immuno-oncology and translational research that includes clinically relevant actionable genes and pathways. A comparable analysis was performed using gene set enrichment analysis (GSEA). Conclusions: The mathematical way in which neural networks reach conclusions has been considered a black box, but a careful understanding and evaluation of the architectural design allows us to interpret the results logically. In diffuse large B-cell lymphoma, neural networks are a plausible data analysis approach. Full article

The concept of gray-zone lymphoma (GZL) has been progressively refined since its introduction in the literature in 1998. For several years, it was applied to a rather broad spectrum of conditions, posing the problem of the differential diagnosis between any type of Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma, with special reference to primary mediastinal forms (PMBL). Officially recognised as a provisional entity in the 4th and revised 4th editions of the WHO Classification of Tumour of Haematopoietic and Lymphoid Tissues with the term “B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and classic Hodgkin lymphoma”, it was limited to tumours showing either morphologic features reminiscent of classic HL (CHL) but carrying a complete B-cell phenotype or conversely provided with a PMBL morphology yet revealing CHL phenotypic characteristics. The definition of GZL has been further revised in the recently published International Lymphoma Classification and 5th edition of the WHO Classification of Haematolymphoid Tumours, which have limited it to mediastinal neoplasms (MGZL) based on emerging molecular evidence. The aim of this review is to critically discuss the issue of MGZL, as well as in light of the suboptimal response to current therapies. Full article

New insights from genomic studies have had an impact on the definition and the diagnosis of several lymphoid tumors including follicular B-cell lymphomas, aggressive diffuse large B-cell lymphomas, and lymphoproliferations associated with acquired and posttransplant immunodeficiencies. Follicular lymphoma (FL) includes tumors whose behavior varies widely from indolent/early lesions to aggressive/transformed lymphomas. Although some large B-cell lymphomas can be subclassified as specific entities, the majority lack the characteristics necessary for subclassification and, thus, are termed diffuse large B-cell lymphoma, NOS. There have been, however, some changes in the classification of specific subtypes of large B-cell lymphoma as well as the addition of new entities, a few of which are highlighted in this article. The immunodeficiency-related lymphoproliferative disorders are currently divided into four major categories based on the clinical setting in which they arose: primary immune deficiency, post-transplant, HIV infection, and iatrogenic immunosuppression. In the two upcoming classifications systems for hematolymphoid neoplasms, International Consensus Classification (ICC) and WHO-HAEM-5, there is a divergence in the approach to categorize these lesions. Furthermore, whereas the WHO-HAEM-5 confirms the ability to classify a spectrum of EBV+ lesions as EBV+ DLBCL, NOS, the ICC has separated out lesions that are composed of a heterogenous cellular infiltrate into a new separate category, “EBV-positive polymorphic B cell lymphoproliferative disorder, NOS”. Both WHO-HAEM-5 and ICC recognize a number of KSHV/HHV8-associated lymphoid lesions and acknowledge that there is significant overlap among the different lesions. In the future, translation of these innovations in general practice requires further validation. Full article

Lymphoproliferative neoplasms of uncertain biological significance are increasingly encountered due to widespread usage of immunophenotypic and molecular techniques. Considering that clearer biological criteria and patient management have been established for B-cell lymphoproliferative diseases of undetermined significance occurring in the peripheral blood, many issues are still obscure for early lesions detected in lymphoid tissues. Regardless that some categories of lymphoproliferative neoplasms of uncertain biological significance have been recognized by the 4th edition of the WHO, other anecdotal early lymphoproliferative lesions still remain fully undefined. Some early lesions frequently originate from the germinal center, including atypical germinal centers BCL2-negative, an early pattern of large B-cell lymphoma with IRF4 rearrangement, and “in situ” high-grade B lymphomas. Moreover, other early lymphoproliferative lesions arise outside the germinal center and include those developing within the setting of monocytoid B-cell hyperplasia, but they also can be directly or indirectly associated with chronic inflammations. This review aims to summarize the concepts discussed during the IV Workshop organized by the Italian Group of Hematopathology, focus on the state-of-the-art on B-cell lymphoproliferative neoplasms of uncertain biological significance, and offer operative insights to pathologists and clinicians in routine diagnostics. Full article

Histological transformation (HT) to a more aggressive disease–mostly diffuse large B-cell lymphoma–is considered one of the most dismal events in the clinical course of follicular lymphoma (FL). Current knowledge has not found a single biological event specific for HT, although different studies have highlighted common genetic alterations, such as TP53 and CDKN2A/B loss, and MYC translocations, among others. Together, they increase genomic complexity and mutational burden at HT. A better knowledge of HT pathogenesis would presumably help to find diagnostic biomarkers allowing the identification of patients at high-risk of transformation, as well as the discrimination from patients with FL recurrence, and those who remain in remission. This would also help to identify new drug targets and the design of clinical trials for the treatment of transformation. In the present review we provide a comprehensive overview of the genetic events frequently identified in transformed FL contributing to the switch towards aggressive behaviour, and we will discuss current open questions in the field of HT. Full article

Follicular lymphoma (FL), a generally indolent disease that derives from germinal center (GC) B cells, represents around 20–25% of all new lymphomas diagnosed in Western countries. The characteristic t(14;18)(q32;q21) translocation that places the BCL2 oncogene under control of the immunoglobulin heavy-chain enhancer occurs in pro- or pre-B cells. However, additional secondary alterations are required for the development of overt FL, which mainly affects genes involved in epigenetic and transcriptional regulation, signaling and B cell differentiation, the BCR/NF-κB pathway, and proliferation/apoptosis. On the other hand, new insights into the FL pathogenesis suggest that FL lacking the BCL2 translocation might be a distinct biological entity with genomic features different from the classical FL. Although FL is considered an indolent disease, around 10–20% of cases eventually transform to an aggressive lymphoma, usually a diffuse large B cell lymphoma, generally by a divergent evolution process from a common altered precursor cell acquiring genomic alterations involved in the cell cycle and DNA damage responses. Importantly, FL tumor cells require interaction with the microenvironment, which sustains cell survival and proliferation. Although the use of rituximab has improved the outlook of most FL patients, further genomic studies are needed to identify those of high risk who can benefit from innovative therapies. This review provides an updated synopsis of FL, including the molecular and cellular pathogenesis, key events of transformation, and targeted treatments. Full article