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Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent mature B-cell neoplasms with variable clinical presentation and distinct histopathologic features. Recent advances in the biology and molecular characteristics of these lymphomas have further expanded our understanding of the heterogeneous nature of these lymphomas, with increasing recognition of specific disease entities within the broader categories of FL and MZL. Here, we discuss the conclusions of the 2022 International Consensus Classification of Mature Lymphoid Neoplasms (2022 ICC) dealing with FL, and review differences with the proposed WHO 5th Edition classification. We review issues related to grading and alternative forms of FL especially those lacking the genetic hallmark of FL, the t(14;18) chromosomal alteration. Among them, t(14;18)-negative CD23+ follicle center lymphoma has been proposed by the 2022 ICC as a provisional entity. Other follicle center–derived lymphomas such as pediatric-type follicular lymphoma, testicular follicular lymphoma, primary cutaneous follicle center lymphoma, and large B-cell lymphoma with IRF4 rearrangement are considered distinct entities separate from conventional FL. Importantly, large B-cell lymphoma with IRF4 rearrangement introduced as a provisional entity in the WHO 2017 is upgraded to a definite entity in the 2022 ICC. We also discuss diagnostic strategies for recognition of MZLs including splenic MZL, extranodal MZL (MALT lymphoma), and primary nodal MZL. The importance of molecular studies in the distinction among marginal zone lymphoma subtypes is emphasized, as well as their value in the differential diagnosis with other B-cell lymphomas.

The third most common lymphoma, MZL is usually indolent and often a consequence of chronic antigenic stimulation from a pathogen such as Helicobacter pylori or hepatitis C virus. Some MZLs regress with treatment of the infection. Patients with genetic lesions are treated with chemoimmunotherapy.

Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) accounts for 7% to 8% of newly diagnosed lymphomas. Because of its association with infectious causes, such as Helicobacter pylori (HP) or Chlamydophila psittaci (CP), and autoimmune diseases, it has become the paradigm of an antigen-driven malignancy. MALT lymphoma usually displays an indolent course, and watch-and-wait strategies are justified initially in a certain percentage of patients. In patients with gastric MALT lymphoma or ocular adnexal MALT lymphoma, antibiotic therapy against HP or CP, respectively, is the first-line management of choice, resulting in lymphoma response rates from 75% to 80% after HP eradication and from 33% to 65% after antibiotic therapy for CP. In patients who have localized disease that is refractory to antibiotics, radiation is widely applied in various centers with excellent local control, whereas systemic therapies are increasingly being applied, at least in Europe, because of the potentially systemic nature of the disease. Therefore, the objective of this review is to briefly summarize the clinicopathologic characteristics of this distinct type of lymphoma along with current data on management strategies.

Paraneoplastic glomerulonephritis (GN) has been reported in non-Hodgkin lymphoma (NHL), Hodgkin Lymphoma (HL), and chronic lymphocytic leukemia (CLL). Despite descriptions in NHL, very few reports have been documented in marginal zone lymphoma (MZL). In this article, we review the literature of currently known cases of MZL-associated GN and we detail two cases of patients with extra-nodal MZL (EMZL) who both presented with renal failure, fluid overload, and proteinuria which were attributed to GN after a renal biopsy. We discuss the pathology of each renal biopsy in depth and how the diagnosis of GN was made, along with potential mechanisms of how EMZL led to GN. We also discuss the treatments each patient received and whether this led to the resolution of their GN. Both cases highlight the importance of maintaining a high index of suspicion for this paraneoplastic syndrome when patients present with signs or symptoms of renal failure, proteinuria or hematuria, or potential renal involvement on imaging. In these cases, a renal biopsy should be pursued to confirm the diagnosis, and treatment should be tailored accordingly.

This meta-analysis aims to concisely summarize the genetic landscape of splenic, nodal and extranodal marginal zone lymphomas (MZL) in the dura mater, salivary glands, thyroid, ocular adnexa, lung, stomach and skin with respect to somatic variants. A systematic PubMed search for sequencing studies of MZL was executed. All somatic mutations of the organs mentioned above were combined, uniformly annotated, and a dataset containing 25 publications comprising 6016 variants from 1663 patients was created. In splenic MZL, KLF2 (18%, 103/567) and NOTCH2 (16%, 118/725) were the most frequently mutated genes. Pulmonary and nodal MZL displayed recurrent mutations in chromatin-modifier-encoding genes, especially KMT2D (25%, 13/51, and 20%, 20/98, respectively). In contrast, ocular adnexal, gastric, and dura mater MZL had mutations in genes encoding for NF-κB pathway compounds, in particular TNFAIP3, with 39% (113/293), 15% (8/55), and 45% (5/11), respectively. Cutaneous MZL frequently had FAS mutations (63%, 24/38), while MZL of the thyroid had a higher prevalence for TET2 variants (61%, 11/18). Finally, TBL1XR1 (24%, 14/58) was the most commonly mutated gene in MZL of the salivary glands. Mutations of distinct genes show origin-preferential distribution among nodal and splenic MZL as well as extranodal MZL at/from different anatomic locations. Recognition of such mutational distribution patterns may help assigning MZL origin in difficult cases and possibly pave the way for novel more tailored treatment concepts.

Mucosa‐associated lymphoid tissue (MALT) lymphoma is an extranodal low‐grade non‐Hodgkin lymphoma that extremely rarely localises to the mediastinum. A 34‐year‐old female with chronic arthralgia, sicca and rash was found to have a well‐demarcated mediastinal cystic mass with equivocal nodular enhancement within the cystic wall on chest CT during a workup for Sjögren's syndrome. Subsequent 68 Ga‐Pentixafor‐PET/CT revealed focal uptake increase within the cystic capsule. The patient underwent thoracoscopic resection of the mediastinal lesion, and pathology revealed MALT lymphoma in the wall of a thymic cyst. This case highlights that 68 Ga‐pentixafor PET/CT could be valuable for the non‐invasive detection of occult thymic MALT lymphoma. Trial Registration: ClinicalTrials.gov . ( www.clinicaltrials.gov , NCT06086327)

Marginal zone lymphoma (MZL) is a rare, indolent form of non-Hodgkin lymphoma that arises from B cells in the marginal zone of lymphoid tissues. MZL comprises 3 key subtypes: extranodal, nodal, and splenic MZL. Despite being generally slow growing, MZL presents significant challenges due to its heterogeneous nature, inconsistently defined disease, and the limited efficacy and availability of current treatments. Advancements in targeted therapies and a deeper understanding of the molecular underpinnings of MZL are critical to improving patient outcomes and achieving more durable remissions. At the Lymphoma Research Foundation’s 2024 Marginal Zone Lymphoma Virtual Scientific Workshop, researchers gathered to discuss recent developments in both basic scientific and clinical research so that together we can continue to develop our understanding of MZL and improve outcomes for patients. This report, which includes a summary of each presentation, aims to review the findings presented at the workshop. Additionally, it highlights opportunities, reviews questions, and assesses areas for future study to set the stage for treatment advancements in the coming decades.

Session 3 of the lymphoma workshop of the XXI joint meeting of the European Association for Haematopathology and the Society for Hematopathology took place in Florence, Italy, on September 22, 2022. The topics of this session were splenic and nodal marginal zone lymphomas, transformation in marginal zone lymphomas, and pediatric nodal marginal zone lymphomas and their differential diagnosis as well as related entities. Forty-two cases in these categories were submitted to the workshop, including splenic lymphomas (marginal zone and diffuse red pulp lymphomas), transformed marginal zone lymphomas (splenic and nodal), nodal marginal zone lymphomas with increased TFH-cells, and pediatric nodal marginal zone lymphomas. The case review highlighted some of the principal problems in the diagnosis of marginal zone lymphomas, including the difficulties in the distinction between splenic marginal zone lymphoma, splenic diffuse red pulp lymphoma, and hairy cell leukemia variant/splenic B-cell lymphoma with prominent nucleoli which requires integration of clinical features, immunophenotype, and morphology in blood, bone marrow, and spleen; cases of marginal zone lymphoma with markedly increased TFH-cells, simulating a T-cell lymphoma, where molecular studies (clonality and mutation detection) can help to establish the final diagnosis; the criteria for transformation of marginal zone lymphomas, which are still unclear and might require the integration of morphological and molecular data; the concept of an overlapping spectrum between pediatric nodal marginal zone lymphoma and pediatric-type follicular lymphoma; and the distinction between pediatric nodal marginal zone lymphoma and “atypical” marginal zone hyperplasia, where molecular studies are mandatory to correctly classify cases.

Nowhere has the divide between advocates and critics of globalization been more striking than in debates over free trade and the environment. And yet the literature on the subject is high on rhetoric and low on results. This book is the first to systematically investigate the subject using both economic theory and empirical analysis. Brian Copeland and Scott Taylor establish a powerful theoretical framework for examining the impact of international trade on local pollution levels, and use it to offer a uniquely integrated treatment of the links between economic growth, liberalized trade, and the environment. The results will surprise many. The authors set out the two leading theories linking international trade to environmental outcomes, develop the empirical implications, and examine their validity using data on measured sulfur dioxide concentrations from over 100 cities worldwide during the period from 1971 to 1986. The empirical results are provocative. For an average country in the sample, free trade is good for the environment. There is little evidence that developing countries will specialize in pollution-intensive products with further trade. In fact, the results suggest just the opposite: free trade will shift pollution-intensive goods production from poor countries with lax regulation to rich countries with tight regulation, thereby lowering world pollution. The results also suggest that pollution declines amid economic growth fueled by economy-wide technological progress but rises when growth is fueled by capital accumulation alone. Lucidly argued and authoritatively written, this book will provide students and researchers of international trade and environmental economics a more reliable way of thinking about this contentious issue, and the methodological tools with which to do so.

ObjectivesTo explore the relevance of T-follicular-helper (Tfh) and pathogenic peripheral-helper T-cells (Tph) in promoting ectopic lymphoid structures (ELS) and B-cell mucosa-associated lymphoid tissue (MALT) lymphomas (MALT-L) in Sjögren’s syndrome (SS) patients.MethodsSalivary gland (SG) biopsies with matched peripheral blood were collected from four centres across the European Union. Transcriptomic (microarray and quantitative PCR) analysis, FACS T-cell immunophenotyping with intracellular cytokine detection, multicolor immune-fluorescence microscopy and in situ hybridisation were performed to characterise lesional and circulating Tfh and Tph-cells. SG-organ cultures were used to investigate functionally the blockade of T-cell costimulatory pathways on key proinflammatory cytokine production.ResultsTranscriptomic analysis in SG identified Tfh-signature, interleukin-21 (IL-21) and the inducible T-cell co-stimulator (ICOS) costimulatory pathway as the most upregulated genes in ELS+SS patients, with parotid MALT-L displaying a 400-folds increase in IL-21 mRNA. Peripheral CD4+CXC-motif chemokine receptor 5 (CXCR5)+programmed cell death protein 1 (PD1)+ICOS+ Tfh-like cells were significantly expanded in ELS+SS patients, were the main producers of IL-21, and closely correlated with circulating IgG and reduced complement C4. In the SG, lesional CD4+CD45RO+ICOS+PD1+ cells selectively infiltrated ELS+ tissues and were aberrantly expanded in parotid MALT-L. In ELS+SG and MALT-L parotids, conventional CXCR5+CD4+PD1+ICOS+Foxp3- Tfh-cells and a uniquely expanded population of CXCR5-CD4+PD1hiICOS+Foxp3- Tph-cells displayed frequent IL-21/interferon-γ double-production but poor IL-17 expression. Finally, ICOS blockade in ex vivo SG-organ cultures significantly reduced the production of IL-21 and inflammatory cytokines IL-6, IL-8 and tumour necrosis factor-α (TNF-α).ConclusionsOverall, these findings highlight Tfh and Tph-cells, IL-21 and the ICOS costimulatory pathway as key pathogenic players in SS immunopathology and exploitable therapeutic targets in SS.