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1
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Li P, Huang Z, Qin Y, Liao W, Xiang T. Diagnosing pulmonary MALT lymphoma: a case of unilateral cystic lesions. Future Sci OA 2025; 11:2497214. [PMID: 40293107 PMCID: PMC12039412 DOI: 10.1080/20565623.2025.2497214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Accepted: 04/09/2025] [Indexed: 04/30/2025] Open
Abstract
We present an atypical case of a 62-year-old female diagnosed with pulmonary mucosa-associated lymphoid tissue (p-MALT) lymphoma, which uniquely manifested as a singular cystic lesion in the lung. Diagnostic evaluations, including comprehensive imaging, bronchoscopy, and CT-guided lung biopsy, revealed this uncommon radiological presentation. Detailed histopathological and immunohistochemical assessments further supported the diagnosis. To determine the extent of the disease, systemic evaluations, such as whole-body PET-CT, gastroscopy, colonoscopy, and bone marrow biopsy, were conducted, confirming its localized nature. Following the definitive diagnosis, the patient underwent a rituximab-centric therapeutic regimen, which yielded significant clinical improvement. This case highlights the importance of recognizing distinctive cystic lung features in p-MALT lymphoma and the indispensable role of holistic diagnostic approaches in guiding precise therapeutic and prognostic decisions.
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Affiliation(s)
- Ping Li
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, Jiangxi, P.R. China
- Jiang Xi Hospital of China-Japan Friendship Hospital, Nanchang, Jiangxi, P.R. China
| | - Zhisheng Huang
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, Jiangxi, P.R. China
| | - Yan Qin
- Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, Jiangxi, P.R. China
| | - Wenjian Liao
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, Jiangxi, P.R. China
| | - Tianxin Xiang
- Jiang Xi Hospital of China-Japan Friendship Hospital, Nanchang, Jiangxi, P.R. China
- Jiangxi Medical Center for Critical Public Health Events, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China
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2
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Du MQ. EMZL at various sites: learning from each other. Blood 2025; 145:2117-2127. [PMID: 39912633 DOI: 10.1182/blood.2024025794] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 12/30/2024] [Accepted: 01/02/2025] [Indexed: 02/07/2025] Open
Abstract
ABSTRACT Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL) invariably develops from a background of chronic inflammatory disorder caused by a diverse chronic microbial infection and/or autoimmunity, depending on the site. These chronic inflammatory/autoimmunity disorders trigger innate and acquired immune responses, generating a unique microenvironment at each site that drives clonal evolution of B cells, their expansion, and eventual malignant transformation. At a molecular level, this involves temporal and spatial acquisition of cooperative oncogenic events by dysregulated immune responses and somatic genetic changes. Although these events are not yet fully characterized, EMZL at several sites shows distinct genetic profiles and molecular insights, bridging the pathologic process to lymphomagenesis. For example, gastric EMZL, particularly those lacking a BCL10 or MALT1 translocation, critically depends on T-helper cell signals produced by immune responses to Helicobacter pylori infection. Likewise, thyroid EMZL may also involve exaggerated T-cell help because of highly frequent inactivating mutations in TET2, CD274 (programmed cell death 1 ligand 1), and TNFRSF14, which impede the coinhibitory interactions between the neoplastic B- and T-helper cells, thus releasing T-cell help. Ocular adnexal EMZL shows frequent TNFAIP3 (A20) mutation/deletion that significantly associates with expression of autoreactive IGHV4-34 B-cell receptor, emphasizing its potential cooperation in NF-κB pathway activation. Finally, the genesis of salivary gland EMZL may be closely associated with GPR34 activation that is caused by mutation/t(X;14)(p11;q32) and/or paracrine stimulation mediated by ligand generated by lymphoepithelial lesions. This review will focus on these novel molecular insights and how these advances may provide a paradigm for future investigations.
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MESH Headings
- Humans
- Lymphoma, B-Cell, Marginal Zone/pathology
- Lymphoma, B-Cell, Marginal Zone/genetics
- Lymphoma, B-Cell, Marginal Zone/immunology
- Lymphoma, B-Cell, Marginal Zone/metabolism
- Lymphoma, B-Cell, Marginal Zone/etiology
- Animals
- Helicobacter Infections/immunology
- Helicobacter Infections/complications
- Helicobacter Infections/pathology
- Helicobacter pylori
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Affiliation(s)
- Ming-Qing Du
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom
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3
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Fu L, Zhou X, Zhang X, Li X, Zhang F, Gu H, Wang X. Circulating tumor DNA in lymphoma: technologies and applications. J Hematol Oncol 2025; 18:29. [PMID: 40069858 PMCID: PMC11900646 DOI: 10.1186/s13045-025-01673-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 02/11/2025] [Indexed: 03/14/2025] Open
Abstract
Lymphoma, a malignant tumor derived from lymphocytes and lymphoid tissues, presents with complex and heterogeneous clinical manifestations, requiring accurate patient classification for appropriate treatment. While invasive pathological examination of lymph nodes or lymphoid tissue remains the gold standard for lymphoma diagnosis, its utility is limited in cases of deep-seated tumors such as intraperitoneal and central nervous system lymphomas. In addition, biopsy procedures carry an inherent risk of complications. Computed tomography (CT) and positron emission tomography/computed tomography (PET/CT) imaging are essential for treatment assessment and monitoring, but lack the ability to detect early clonal evolution and minimal residual disease (MRD). Liquid biopsy-based analysis of circulating tumor DNA (ctDNA) offers a non-invasive alternative that allows for repeated sampling and overcomes the limitations of spatial heterogeneity and invasive biopsies. ctDNA provides genetic and epigenetic insights into lymphoma and serves as a dynamic, quantifiable biomarker for diagnosis, risk stratification, and treatment response. This review comprehensively summarizes common genetic variations in lymphoma and systematically evaluates ctDNA detection technologies, including PCR-based assays and next-generation sequencing (NGS). Applications of ctDNA detection in noninvasive genotyping, risk stratification, therapeutic response monitoring, and MRD detection are discussed across various lymphoma subtypes, including diffuse large B-cell lymphoma, Hodgkin lymphoma, follicular lymphoma, and T-cell lymphoma. By integrating recent research findings, the review highlights the role of ctDNA profiling in advancing precision medicine, enabling personalized therapeutic strategies, and improving clinical outcomes in lymphoma.
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Affiliation(s)
- Lina Fu
- Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, Anhui Province, China
- Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, 230031, Anhui Province, China
| | - Xuerong Zhou
- Department of Hematology, The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, China
| | - Xiaoyu Zhang
- Department of Hematology, Qilu Hospital of Shandong University, Shandong Province, 250012, Jinan, China
| | - Xuhua Li
- Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, Anhui Province, China
- Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, 230031, Anhui Province, China
| | - Fan Zhang
- Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, Anhui Province, China
- Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, 230031, Anhui Province, China
| | - Hongcang Gu
- Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, Anhui Province, China.
- Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, 230031, Anhui Province, China.
| | - Xiaoxue Wang
- Department of Hematology, The First Hospital of China Medical University, Shenyang, 110001, Liaoning Province, China.
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Segura-Rivera R, Pina-Oviedo S. Marginal zone lymphoma of extranodal sites: A review with an emphasis on diagnostic pitfalls and differential diagnosis with reactive conditions. Hum Pathol 2025; 156:105683. [PMID: 39542179 DOI: 10.1016/j.humpath.2024.105683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 11/09/2024] [Accepted: 11/11/2024] [Indexed: 11/17/2024]
Abstract
Marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) represents 8% of all B-cell lymphomas and it is the most common small B-cell lymphoma arising at extranodal sites. The gold-standard test to establish a diagnosis of MALT lymphoma remains histopathologic analysis with the aid of immunohistochemistry (IHC) and/or flow cytometry immunophenotypic analysis. MALT lymphoma represents a progression from a persistent chronic inflammatory process, and therefore distinguishing MALT lymphoma from chronic inflammation by histopathology may be challenging in some cases. Despite recent trends to consider IGH rearrangement/clonality as a confirmatory diagnostic test of MALT lymphoma, this method is far from ideal for this purpose since a positive or a negative result does not necessarily confirm or exclude that a process is lymphoma or reactive. This test must be correlated with the morphologic findings. Moreover, MALT lymphoma may arise in association with underlying autoimmune conditions where clonal lymphoid populations are not uncommonly detected. Therefore, we believe that an integrated approach including detailed morphologic review in combination with IHC and/or flow cytometry is best to establish a diagnosis of MALT lymphoma in most cases. We present helpful morphologic tips to avoid potential diagnostic pitfalls at some of the most common extranodal sites, including the stomach, ocular adnexa/conjunctiva, salivary gland, lung, thymus, breast, thyroid, small and large intestine and the dura. The differential diagnosis of MALT lymphoma with IgG4-related disease is also discussed.
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Affiliation(s)
| | - Sergio Pina-Oviedo
- Department of Pathology, Duke University Medical Center, Durham, NC, USA.
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Steinbrecher O, Kiesewetter B, Dolak W, Brand R, Simonitsch‐Klupp I, Raderer M. Clinicopathological Characteristics of Extranodal Marginal Zone Lymphoma of the Mucosa Associated Lymphoid Tissue (MALT-Lymphoma) of the Intestine: A Single Center Analysis. Hematol Oncol 2025; 43:e70007. [PMID: 39624879 PMCID: PMC11612847 DOI: 10.1002/hon.70007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 11/07/2024] [Accepted: 11/16/2024] [Indexed: 12/06/2024]
Abstract
Extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT-lymphoma) is an indolent B-cell lymphoma with a distinct affinity for mucosal structures. Most commonly arising in the stomach, only roughly 2% of MALT-lymphomas occur in the colon or the intestine. In view of this, we have retrospectively assessed all patients with MALT-lymphoma involving the intestine for clinicopathological characteristics. Data of all patients with MALT-lymphoma and intestinal involvement (i.e. both primary and secondary), treated and followed at the Medical University of Vienna between 1999 and 2021 were retrospectively collected from hospital records and analyzed. Differences in baseline and therapy characteristics, as well as survival between primary and secondary, and between intestinal and gastric MALT-lymphoma (as the most common subgroup of patients) were investigated. In total, 42 patients were identified; 24/484 (5%) were classified as primary and 18 (3.7%) as secondary intestinal MALT-lymphomas. The most common primary intestinal location was the colon (10/24) and the most frequent primary site in the 18 cases with secondary intestinal MALT-lymphomas was the stomach (14/18). A total of 28/42 (66.7%) patients presented with LUGANO stage I, 7/42 (16.7%) with stage II/IIE and 7/42 (16.7%) with stage IV disease. Translocation t (11; 18) (q21; q21) was positive in 47% of patients with secondary and 25% of primary intestinal MALT-lymphomas. Median OS in for intestinal MALT-lymphoma was 301 months (95% CI n.a.) with 89.1% alive at 5 years and 77.2% alive at 10 years. Median PFS in the entire cohort was 50.4 months (95% CI 38.4-62.4 months), with an overall response rate and disease control rate of 73% and 97.3%, respectively. No difference in OS and PFS between primary and secondary intestinal, as well as between intestinal and gastric MALT-lymphoma was detected. Our data suggest that dissemination within the GI tract does not seem to be an adverse prognostic feature and highlights the preferred use of the Lugano staging system in such patients, which also summarizes multiple lesions within the GI-tract as Stage I.
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Affiliation(s)
- Oskar Steinbrecher
- Division of OncologyDepartment of Medicine IMedical University of ViennaViennaAustria
| | - Barbara Kiesewetter
- Division of OncologyDepartment of Medicine IMedical University of ViennaViennaAustria
| | - Werner Dolak
- Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria
| | - Rosa Brand
- Department of PathologyMedical University of ViennaViennaAustria
| | | | - Markus Raderer
- Division of OncologyDepartment of Medicine IMedical University of ViennaViennaAustria
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6
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Han Y, Wu R, Zhang Y, Zhang X, Gao Z. 18F-FDG PET/CT findings in a mucosa-associated lymphoid tissue lymphoma patient coexisting with primary myelofibrosis. AMERICAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 2024; 14:365-370. [PMID: 39840377 PMCID: PMC11744357 DOI: 10.62347/bzuz7442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 12/09/2024] [Indexed: 01/23/2025]
Abstract
A 61-year-old male presented with hematemesis and melena. Biopsy and immunohistochemistry confirmed mucosa-associated lymphoid tissue (MALT) lymphoma in the posterior wall of the gastric antrum, prompting further evaluation with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). In addition to elevated uptake in the gastric antrum, 18F-FDG PET/CT showed diffuse uptake in multiple bone marrow, initially suspected to indicate bone marrow involvement by lymphoma. Further examination identified it as primary myelofibrosis (PMF). Following concurrent therapies, 18F-FDG PET/CT demonstrated negative uptake in gastric antrum, indicating complete remission of the lymphoma, while the elevated bone marrow uptake suggested progression of PMF. The coexistence of MALT lymphoma and PMF is very rare. This case highlights the image characteristics and potential diagnostic and therapeutic monitoring value of 18F-FDG PET/CT in patients with concurrent MALT lymphoma and PMF.
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Affiliation(s)
- Yanmei Han
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan 430022, Hubei, China
- Hubei Key Laboratory of Molecular ImagingWuhan 430022, Hubei, China
- Key Laboratory of Biological Targeted Therapy, The Ministry of EducationWuhan 430022, Hubei, China
| | - Ruolin Wu
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan 430022, Hubei, China
- Hubei Key Laboratory of Molecular ImagingWuhan 430022, Hubei, China
- Key Laboratory of Biological Targeted Therapy, The Ministry of EducationWuhan 430022, Hubei, China
| | - Yajing Zhang
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan 430022, Hubei, China
- Hubei Key Laboratory of Molecular ImagingWuhan 430022, Hubei, China
- Key Laboratory of Biological Targeted Therapy, The Ministry of EducationWuhan 430022, Hubei, China
| | - Xiao Zhang
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan 430022, Hubei, China
- Hubei Key Laboratory of Molecular ImagingWuhan 430022, Hubei, China
- Key Laboratory of Biological Targeted Therapy, The Ministry of EducationWuhan 430022, Hubei, China
| | - Zairong Gao
- Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan 430022, Hubei, China
- Hubei Key Laboratory of Molecular ImagingWuhan 430022, Hubei, China
- Key Laboratory of Biological Targeted Therapy, The Ministry of EducationWuhan 430022, Hubei, China
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7
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Liang PS, Shih HJ, Huang SH, Chen YZ. Primary lymphoma of mucosa associated lymphoid tissue (MALT lymphoma) in the urinary bladder mimicking recurrent urinary tract infection: a case report and literature review. BMC Urol 2024; 24:223. [PMID: 39395994 PMCID: PMC11470736 DOI: 10.1186/s12894-024-01616-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 10/01/2024] [Indexed: 10/14/2024] Open
Abstract
We report the case of a 79-year-old woman with primary lymphoma of mucosa-associated lymphoid tissue (MALT) in the urinary bladder. The patient, with urinary frequency, urgency and suprapubic pain had several emergency room visits due to recurrent urinary tract infection. Both sonogram and cystoscopy identified bladder tumors near the bladder neck. An abdominal contrast-enhanced computed tomography scan revealed a polypoid lesion on the anterior bladder wall without enlarged lymph nodes. Transurethral resection of the bladder tumor was conducted. The pathology report confirmed extranodal marginal zone MALT lymphoma. The clinical stage was IEA. Follow-up imaging reported residual bladder tumors, prompting adjuvant radiotherapy. The patient was treated successfully and was disease-free at the 9-month follow-up visit. Primary lymphoma is an uncommon pathological subtype. Its clinical and radiological differentiation from urothelial carcinoma (UC) can be challenging, but treatment strategies differ significantly. A definitive diagnosis relies on histopathology and immunohistochemistry. Typically, bladder lymphoma has a favorable prognosis, but further research is required to identify the optimal treatment.
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Affiliation(s)
- Po-Sung Liang
- Division of Urology, Department of Surgery, Changhua Christian Hospital, Changhua City, Changhua County, Taiwan
| | - Hung-Jen Shih
- Division of Urology, Department of Surgery, Changhua Christian Hospital, Changhua City, Changhua County, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Sheng-Hsien Huang
- Division of Urology, Department of Surgery, Changhua Christian Hospital, Changhua City, Changhua County, Taiwan
| | - Yi-Zhong Chen
- Division of Urology, Department of Surgery, Changhua Christian Hospital, Changhua City, Changhua County, Taiwan.
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8
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Shirriff AS, Tauchi-Nishi PS, Hayashida KM, Sweeney AR. Orbital extranodal marginal zone lymphoma arising during pregnancy: a case report. Orbit 2024; 43:501-504. [PMID: 36880178 DOI: 10.1080/01676830.2023.2186433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 02/25/2023] [Indexed: 03/08/2023]
Abstract
A 37-year-old, previously healthy woman presented during her first trimester of pregnancy with a two-week history of rapidly progressive proptosis in the left eye. Clinical examination revealed limited left supraduction and diplopia in upward gaze. Orbital magnetic resonance imaging showed a medial orbital mass adjacent to the globe with secondary proptosis. Pathologic examination of a biopsied specimen of the orbital mass and subsequent immunophenotyping by flow cytometry revealed an extranodal marginal zone B-cell lymphoma. Clinical and histological features as well as a review of the literature are described.
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Affiliation(s)
- Ashley S Shirriff
- John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA
| | - Pamela S Tauchi-Nishi
- Department of Pathology, John A. Burns School of Medicine,University of Hawaii, Honolulu, Hawaii, USA
- Department of Pathology, Queen's Medical Center, Honolulu, Hawaii, USA
| | - Karin M Hayashida
- Department of Obstetrics and Gynecology, Kaiser Permanente Hawaii, Honolulu, Hawaii, USA
| | - Adam R Sweeney
- Section of Ophthalmology, Department of Surgery, University of Hawaii John A Burns School of Medicine, Honolulu, Hawaii, USA
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9
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Silkenstedt E, Salles G, Campo E, Dreyling M. B-cell non-Hodgkin lymphomas. Lancet 2024; 403:1791-1807. [PMID: 38614113 DOI: 10.1016/s0140-6736(23)02705-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 07/31/2023] [Accepted: 11/30/2023] [Indexed: 04/15/2024]
Abstract
B-cell lymphomas occur with an incidence of 20 new cases per 100 000 people per year in high-income countries. They can affect any organ and are characterised by heterogeneous clinical presentations and courses, varying from asymptomatic, to indolent, to very aggressive cases. Since the topic of B-cell non-Hodgkin lymphomas was last reviewed in The Lancet in 2017, a deeper understanding of the biological background of this heterogeneous group of malignancies, the availability of new diagnostic methods, and the development and implementation of new targeted and immunotherapeutic approaches have improved our ability to treat patients. This Seminar provides an overview of the pathobiology, classification, and prognostication of B-cell non-Hodgkin lymphomas and summarises the current knowledge and standard of care regarding biology and clinical management of the most common subtypes of mature B-cell non-Hodgkin lymphomas. It also highlights new findings in deciphering the molecular background of disease development and the implementation of new therapeutic approaches, particularly those targeting the immune system.
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Affiliation(s)
| | - Gilles Salles
- Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
| | - Elias Campo
- Department of Pathology, Hospital Clinic, Institute for Biomedical Research August Pi i Sunyer, University of Barcelona, Barcelona, Spain
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10
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Verhelst SHL, Prothiwa M. Chemical Probes for Profiling of MALT1 Protease Activity. Chembiochem 2023; 24:e202300444. [PMID: 37607867 DOI: 10.1002/cbic.202300444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 08/20/2023] [Accepted: 08/22/2023] [Indexed: 08/24/2023]
Abstract
The paracaspase MALT1 is a key regulator of the human immune response. It is implicated in a variety of human diseases. For example, deregulated protease activity drives the survival of malignant lymphomas and is involved in the pathophysiology of autoimmune/inflammatory diseases. Thus, MALT1 has attracted attention as promising drug target. Although many MALT1 inhibitors have been identified, molecular tools to study MALT1 activity, target engagement and inhibition in complex biological samples, such as living cells and patient material, are still scarce. Such tools are valuable to validate MALT1 as a drug target in vivo and to assess yet unknown biological roles of MALT1. In this review, we discuss the recent literature on the development and biological application of molecular tools to study MALT1 activity and inhibition.
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Affiliation(s)
- Steven H L Verhelst
- Department of Cellular and Molecular Medicine, KU Leuven - University of Leuven, Herestraat 49, box 901b, 3000, Leuven, Belgium
- Leibniz Institut für Analytische Wissenschaften - ISAS - e.V., Otto-Hahn Strasse 6b, 44227, Dortmund, Germany
| | - Michaela Prothiwa
- Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium
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11
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Dumitru AV, Țăpoi DA, Halcu G, Munteanu O, Dumitrascu DI, Ceaușu MC, Gheorghișan-Gălățeanu AA. The Polyvalent Role of CD30 for Cancer Diagnosis and Treatment. Cells 2023; 12:1783. [PMID: 37443818 PMCID: PMC10341339 DOI: 10.3390/cells12131783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 07/01/2023] [Accepted: 07/03/2023] [Indexed: 07/15/2023] Open
Abstract
CD30, also known as TNFRSF8 (tumor necrosis factor receptor superfamily member 8), is a protein receptor that is heavily glycosylated inside the Golgi apparatus, as well as a tumor marker that is found on the surface of specific cells in the body, including certain immune cells and cancer ones. This review aims to shed light on the critical importance of CD30, from its emergence in the cell to its position in diagnosing various diseases, including Hodgkin lymphoma, where it is expressed on Hodgkin and Reed-Sternberg cells, as well as embryonal carcinoma, anaplastic large cell lymphoma (ALCL), and cutaneous T-cell lymphoma (CTCL). In addition to its role in positive diagnosis, targeting CD30 has been a promising approach treating CD30-positive lymphomas, and there is ongoing research into the potential use of CD30-targeted therapies for autoimmune disorders. We aim to elaborate on CD30's roles as a tumor marker, supporting thus the hypothesis that this receptor might be the aim of cytostatic treatment.
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Affiliation(s)
- Adrian Vasile Dumitru
- Department of Pathology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.V.D.); (M.C.C.)
- Department of Pathology, University Emergency Hospital, 050098 Bucharest, Romania
| | - Dana Antonia Țăpoi
- Department of Pathology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.V.D.); (M.C.C.)
- Department of Pathology, University Emergency Hospital, 050098 Bucharest, Romania
| | - Georgian Halcu
- Department of Pathology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.V.D.); (M.C.C.)
- Department of Pathology, Colțea Clinical Hospital, 030171 Bucharest, Romania
| | - Octavian Munteanu
- Department of Anatomy, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania;
- Department of Obstetrics and Gynecology, University Emergency Hospital, 050098 Bucharest, Romania
| | - David-Ioan Dumitrascu
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania;
| | - Mihail Constantin Ceaușu
- Department of Pathology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.V.D.); (M.C.C.)
- Department of Pathology, Alexandru Trestioreanu Institute of Oncology, 022328 Bucharest, Romania
| | - Ancuța-Augustina Gheorghișan-Gălățeanu
- Department of Cellular and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania;
- C.I. Parhon National Institute of Endocrinology, 011863 Bucharest, Romania
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12
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Raderer M, Kiesewetter B, Du MQ. Clinical relevance of molecular aspects in extranodal marginal zone lymphoma: a critical appraisal. Ther Adv Med Oncol 2023; 15:17588359231183565. [PMID: 37389189 PMCID: PMC10302523 DOI: 10.1177/17588359231183565] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Accepted: 05/24/2023] [Indexed: 07/01/2023] Open
Abstract
Extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) is among the more common types of lymphoma accounting for up to 8% of newly diagnosed lymphoma cases. As opposed to other B-cell lymphomas, however, no predominant genetic hallmark has been defined in MALT lymphoma, but different localizations appear to be affected by different, sometimes distinct changes. Nonetheless, a high proportion of these genetic changes reported in MALT lymphomas dysregulate the pathways leading to NF-kB activation. t(11;18)(q21;q21)/BIRC3::MALT1 appears to be MALT lymphoma specific and is found in 24% of gastric and 40% of pulmonary MALT lymphomas. The translocation is associated with more disseminated disease in gastric MALT lymphoma and is found in a large percentage of patients whose lymphoma is unresponsive to antibiotic eradication of Helicobacter pylori. In addition to t(11;18)(q21;q21), nuclear expression of BCL10 or NF-kB appears to be highly associated with lymphoma cell survival independence of H. pylori-mediated stimulations. Antibiotic eradication, however, is the recommended therapy of choice irrespective of genetic findings, and molecular analysis is not required before initiation of therapy. The influence of genetic translocations including t(11;18)(q21;q21) on systemic therapies, however, is less clearly defined. While small series have shown no influence on the outcome for treatment with the anti-CD20 antibody rituximab (R) or treatment with cladribine (2-CdA), conflicting data have been reported for alkylating agents, especially chlorambucil and the combination of R + chlorambucil. None of other genetic changes seen in MALT lymphoma to date has discernible value in routine clinical applications, but recent data suggest that changes in TNFAIP3(A20), KMTD2 and CARD11 might be associated with response to Bruton kinase inhibitors.
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Affiliation(s)
| | - Barbara Kiesewetter
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Austria
| | - Ming-Qing Du
- Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK
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13
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Sreenivasan S, Solanki R, Kancharla P, Khan C, Samhouri Y. A Meningioma Mimic and Distinct Subtype of Primary Central Nervous System Lymphoma: Primary Dural Lymphoma. J Hematol 2023; 12:87-91. [PMID: 37187500 PMCID: PMC10181329 DOI: 10.14740/jh1113] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Accepted: 04/24/2023] [Indexed: 05/17/2023] Open
Abstract
Primary central nervous system lymphoma (PCNSL) is an aggressive form of extranodal non-Hodgkin lymphoma that arises in the brain parenchyma, eyes, meninges, or spinal cord in the absence of systemic disease. Primary dural lymphoma (PDL), in contrast, arises from the dura mater of the brain. PDL is usually a low-grade B-cell marginal zone lymphoma (MZL), whereas other types of PCNSL are usually high-grade large B-cell lymphoma. This specific pathological subtype has important therapeutic and prognostic implications, making PDL a distinct subtype of PCNSL. Herein, we report a case of PDL in an African American patient, in her late thirties, who presented to our emergency room with chronic headaches. An emergent magnetic resonance imaging (MRI) of the brain showed a dural-based homogeneously enhancing extra-axial mass along the left hemisphere, which was contained within the anterior and parietal dural mater. A surgical specimen was collected after an emergency debulking procedure. The flow cytometry, done on the surgical specimen obtained, was positive for CD19+, CD20+, and CD22+, but negative for CD5- and CD10-. These findings were consistent with a clonal B-lymphoproliferative disorder. The surgical pathology specimen immunohistochemistry was positive for CD20+ and CD45+, but negative for Bcl-6Cyclin D1- and CD56-. The Ki67 was 10-20%. These findings were consistent with extranodal MZL. Given the location and pathology, the patient was diagnosed with PDL. Due to MZL's indolent nature, location outside the blood-brain barrier, and known efficacy to bendamustine-rituximab (BR), we decided to treat our patient with BR. She completed six cycles without major complications, and her post-therapy brain MRI showed complete remission (CR). Our case adds to the sparse literature about PDL and highlights the efficacy of BR systemic chemotherapy on MZLs.
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Affiliation(s)
- Sushanth Sreenivasan
- Department of Internal Medicine, West Penn Hospital, Pittsburgh, PA, USA
- Corresponding Author: Sushanth Sreenivasan, Department of Internal Medicine, West Penn Hospital, Pittsburgh, PA, USA.
| | - Risha Solanki
- Division of Hematology and Cellular Therapy, Allegheny Health Network Cancer Institute, Pittsburgh, PA, USA
| | - Pragnan Kancharla
- Division of Hematology and Cellular Therapy, Allegheny Health Network Cancer Institute, Pittsburgh, PA, USA
| | - Cyrus Khan
- Division of Hematology and Cellular Therapy, Allegheny Health Network Cancer Institute, Pittsburgh, PA, USA
| | - Yazan Samhouri
- Division of Hematology and Cellular Therapy, Allegheny Health Network Cancer Institute, Pittsburgh, PA, USA
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14
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Kim SH, Soliman Y, Chitnavis VN, Chitnavis MV. Helicobacter Pylori-Negative MALT Lymphoma: A Series of Two Cases Presenting with Life-Threatening Upper Gastrointestinal Bleeding. Case Rep Gastrointest Med 2023; 2023:8244696. [PMID: 37009207 PMCID: PMC10063354 DOI: 10.1155/2023/8244696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Revised: 01/23/2023] [Accepted: 02/27/2023] [Indexed: 04/04/2023] Open
Abstract
Mucosa-associated lymphoid tissue (MALT) lymphoma is a common cause of gastric lymphoma. Although most cases are associated with an H. pylori infection, approximately 10% are H. pylori-negative. Patients with gastric MALT lymphoma are usually asymptomatic or present with nonspecific symptoms such as abdominal pain, dyspepsia, weight loss, and occult gastrointestinal bleeding. In this report, we describe two patients with H. pylori-negative MALT lymphoma who both presented with acute upper gastrointestinal bleeding that led to hemodynamic instability. After resuscitation, emergent endoscopy was performed. Both patients had the t (11; 18) (q21; q21) translocation, which prompted direct treatment by radiotherapy.
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Affiliation(s)
- Seo Hyun Kim
- Virginia Tech Carilion School of Medicine, Roanoke, VA, USA
| | | | - Vikas N. Chitnavis
- Department of Internal Medicine, Division of Gastroenterology, Carilion Clinic and Virginia Tech Carilion School of Medicine, Roanoke, VA, USA
| | - Maithili V. Chitnavis
- Inflammatory Bowel Disease Section, Atrium Health Gastroenterology, Charlotte, NC, USA
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15
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Old and New Facts and Speculations on the Role of the B Cell Receptor in the Origin of Chronic Lymphocytic Leukemia. Int J Mol Sci 2022; 23:ijms232214249. [PMID: 36430731 PMCID: PMC9693457 DOI: 10.3390/ijms232214249] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 11/09/2022] [Accepted: 11/11/2022] [Indexed: 11/19/2022] Open
Abstract
The engagement of the B cell receptor (BcR) on the surface of leukemic cells represents a key event in chronic lymphocytic leukemia (CLL) since it can lead to the maintenance and expansion of the neoplastic clone. This notion was initially suggested by observations of the CLL BcR repertoire and of correlations existing between certain BcR features and the clinical outcomes of single patients. Based on these observations, tyrosine kinase inhibitors (TKIs), which block BcR signaling, have been introduced in therapy with the aim of inhibiting CLL cell clonal expansion and of controlling the disease. Indeed, the impressive results obtained with these compounds provided further proof of the role of BcR in CLL. In this article, the key steps that led to the determination of the role of BcR are reviewed, including the features of the CLL cell repertoire and the fine mechanisms causing BcR engagement and cell signaling. Furthermore, we discuss the biological effects of the engagement, which can lead to cell survival/proliferation or apoptosis depending on certain intrinsic cell characteristics and on signals that the micro-environment can deliver to the leukemic cells. In addition, consideration is given to alternative mechanisms promoting cell proliferation in the absence of BcR signaling, which can explain in part the incomplete effectiveness of TKI therapies. The role of the BcR in determining clonal evolution and disease progression is also described. Finally, we discuss possible models to explain the selection of a special BcR set during leukemogenesis. The BcR may deliver activation signals to the cells, which lead to their uncontrolled growth, with the possible collaboration of other still-undefined events which are capable of deregulating the normal physiological response of B cells to BcR-delivered stimuli.
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16
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Chifiriuc MC, Filip R, Constantin M, Pircalabioru GG, Bleotu C, Burlibasa L, Ionica E, Corcionivoschi N, Mihaescu G. Common themes in antimicrobial and anticancer drug resistance. Front Microbiol 2022; 13:960693. [PMID: 36003940 PMCID: PMC9393787 DOI: 10.3389/fmicb.2022.960693] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 07/22/2022] [Indexed: 11/13/2022] Open
Abstract
Antimicrobial and anticancer drug resistance represent two of the main global challenges for the public health, requiring immediate practical solutions. In line with this, we need a better understanding of the origins of drug resistance in prokaryotic and eukaryotic cells and the evolutionary processes leading to the occurrence of adaptive phenotypes in response to the selective pressure of therapeutic agents. The purpose of this paper is to present some of the analogies between the antimicrobial and anticancer drug resistance. Antimicrobial and anticancer drugs share common targets and mechanisms of action as well as similar mechanisms of resistance (e.g., increased drug efflux, drug inactivation, target alteration, persister cells’ selection, protection of bacterial communities/malignant tissue by an extracellular matrix, etc.). Both individual and collective stress responses triggered by the chemotherapeutic agent involving complex intercellular communication processes, as well as with the surrounding microenvironment, will be considered. The common themes in antimicrobial and anticancer drug resistance recommend the utility of bacterial experimental models for unraveling the mechanisms that facilitate the evolution and adaptation of malignant cells to antineoplastic drugs.
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Affiliation(s)
- Mariana Carmen Chifiriuc
- Faculty of Biology, University of Bucharest, Bucharest, Romania
- Life, Environmental and Earth Sciences Division, Research Institute of the University of Bucharest, Bucharest, Romania
- The Romanian Academy, Bucharest, Romania
- Academy of Romanian Scientists, Bucharest, Romania
| | - Roxana Filip
- Faculty of Medicine and Biological Sciences, Stefan cel Mare University of Suceava, Suceava, Romania
- Suceava Emergency County Hospital, Suceava, Romania
| | | | - Gratiela Gradisteanu Pircalabioru
- Faculty of Biology, University of Bucharest, Bucharest, Romania
- Academy of Romanian Scientists, Bucharest, Romania
- *Correspondence: Gratiela Gradisteanu Pircalabioru,
| | - Coralia Bleotu
- Stefan S. Nicolau Institute of Virology, Bucharest, Romania
- Romanian Academy of Scientists, Bucharest, Romania
- Coralia Bleotu, ;
| | | | - Elena Ionica
- Faculty of Biology, University of Bucharest, Bucharest, Romania
| | - Nicolae Corcionivoschi
- Bacteriology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, Belfast, United Kingdom
- Faculty of Bioengineering of Animal Resources, Banat University of Agricultural Sciences and Veterinary Medicine—King Michael I of Romania, Timisoara, Romania
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17
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McGrath LA, Ryan DA, Warrier SK, Coupland SE, Glasson WJ. Conjunctival Lymphoma. Eye (Lond) 2022; 37:837-848. [PMID: 35882984 PMCID: PMC10049989 DOI: 10.1038/s41433-022-02176-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 06/20/2022] [Accepted: 07/01/2022] [Indexed: 11/09/2022] Open
Abstract
Lymphoma of the conjunctiva is an ocular malignancy derived from clonal proliferation of lymphocytes. The majority of conjunctival lymphoma is extranodal marginal zone B-Cell lymphoma (EMZL), however diffuse large B-cell (DLBCL), follicular (FL), mantle cell (MCL) and T- cell subtypes are also seen. Clinical manifestations are non-specific, but include unilateral or bilateral painless salmon-pink conjunctival lesions. Approaches to treatment have centered around local immunomodulation, often with Interferon-α2b or Rituximab (anti-CD20 monoclonal antibody) with or without radiation. Although conjunctival lymphoma is generally considered an indolent disease, recent advances in next-generation sequencing have improved clinicians' ability to predict future recurrence or systemic disease through assessment of cytogenic and molecular features. In this paper, we review the classification, clinical features, diagnostic techniques, and emerging strategies for management and prognostication of conjunctival lymphomas.
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Affiliation(s)
- Lindsay A McGrath
- Queensland Ocular Oncology Service, Terrace Eye Centre, Brisbane, QLD, Australia. .,University of Queensland, School of Medicine, Brisbane, QLD, Australia.
| | - David A Ryan
- Sullivan Nicolaides Pathology, Brisbane, QLD, Australia
| | - Sunil K Warrier
- Queensland Ocular Oncology Service, Terrace Eye Centre, Brisbane, QLD, Australia
| | - Sarah E Coupland
- Liverpool Clinical Laboratories, Liverpool University Hospitals Foundation Trust, Liverpool, UK.,Department. of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, UK
| | - William J Glasson
- Queensland Ocular Oncology Service, Terrace Eye Centre, Brisbane, QLD, Australia.,University of Queensland, School of Medicine, Brisbane, QLD, Australia
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18
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Raderer M, Kiesewetter B, Mayerhoefer ME. Positron emission tomography/magnetic resonance imaging (PET/MRI) vs. gastroscopy: Can it improve detection of extranodal marginal zone lymphomas of the stomach following H. pylori treatment? Expert Rev Hematol 2022; 15:565-571. [PMID: 35695746 DOI: 10.1080/17474086.2022.2089110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION The stomach is the most common site of origin for extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma). Antibiotic eradication of Helicobacter pylori (H. pylori) is the standard first-line treatment, with response assessment being performed by histological evaluation of multiple gastric biopsies. AREAS COVERED The objective of this review is to provide an update on results obtained using noninvasive methods, including magnetic resonance imaging (MRI), positron emission tomography combined with computed tomography (PET/CT), and most recently, PET/MRI for the assessment of disease extent and response to treatment in patients with gastric MALT lymphoma. EXPERT OPINION While CT is the officially recommended imaging technique, few studies in small cohorts have suggested that diffusion-weighted MRI shows higher sensitivity, also relative to 18 F-FDG PET/CT, for both gastric and nongastric MALT lymphomas. A recent prospective study using PET/MRI with the novel CXCR4-targeting radiotracer 68 Ga-Pentixafor suggested that, for patients with gastric MALT lymphoma after H. pylori eradication, this imaging technique may provide excellent accuracy (97%) for assessment of residual or recurrent disease. Although recent studies on CXCR4-targeting PET and to some extent also diffusion-weighted MRI are promising, there is insufficient evidence to suggest a change in clinical practice.
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Affiliation(s)
- Markus Raderer
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - Barbara Kiesewetter
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - Marius E Mayerhoefer
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.,Therapy, Division of General and Pediatric, Radiology, Medical University of Vienna, Department of Biomedical Imaging and Image-guided, Vienna, Austria
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19
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Turning up the heat on salivary gland MALT lymphoma. Blood 2022; 139:2094-2096. [PMID: 35389438 DOI: 10.1182/blood.2021012624] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 06/02/2021] [Indexed: 12/24/2022] Open
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20
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Dehner CA, Ruff WE, Greiling T, Pereira MS, Redanz S, McNiff J, Girardi M, Kriegel MA. Malignant T Cell Activation by a Bacillus Species Isolated from Cutaneous T-Cell Lymphoma Lesions. JID INNOVATIONS 2022; 2:100084. [PMID: 35199089 PMCID: PMC8844718 DOI: 10.1016/j.xjidi.2021.100084] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 10/05/2021] [Accepted: 10/14/2021] [Indexed: 01/04/2023] Open
Abstract
Cutaneous T-cell lymphoma (CTCL) is a life-debilitating malignancy of lymphocytes homing to the skin. Although CTCL is thought to arise from a combination of genetic, epigenetic, and environmental factors, specific triggers are unclear. The skin is colonized by a unique microbiota and is heavily influenced by its interactions. We hypothesized that adaptive immune responses to skin commensals lead to clonal T-cell proliferation and transformation in the appropriate genetic background. We therefore collected lesional and nonlesional skin microbiota from patients with CTCL to study T cell interactions using skin T cell explants and peripheral, skin-homing CD4+ T cells. By various methods, we identified Bacillus safensis in CTCL lesions, a rare human commensal in healthy skin, and showed that it can induce malignant T cell activation and cytokine secretion. Taken together, our data suggest microbial triggers in the skin microbiota of patients with CTCL as potential instigators of tumorigenesis.
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Affiliation(s)
- Carina A. Dehner
- Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA
- Department of Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA
| | - William E. Ruff
- Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Teri Greiling
- Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA
- Department of Dermatology, Oregon Health & Science University, Portland, Oregon, USA
| | - Márcia S. Pereira
- Department of Translational Rheumatology and Immunology, Institute of Musculoskeletal Medicine, University of Münster, Münster, Germany
| | - Sylvio Redanz
- Department of Translational Rheumatology and Immunology, Institute of Musculoskeletal Medicine, University of Münster, Münster, Germany
| | - Jennifer McNiff
- Department of Dermatopathology, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Michael Girardi
- Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Martin A. Kriegel
- Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA
- Department of Translational Rheumatology and Immunology, Institute of Musculoskeletal Medicine, University of Münster, Münster, Germany
- Section of Rheumatology and Clinical Immunology, Department of Medicine, University Hospital Münster, Münster, Germany
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21
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Johansson P, Eckstein A, Küppers R. The Biology of Ocular Adnexal Marginal Zone Lymphomas. Cancers (Basel) 2022; 14:1264. [PMID: 35267569 PMCID: PMC8908984 DOI: 10.3390/cancers14051264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 02/06/2022] [Accepted: 02/23/2022] [Indexed: 02/04/2023] Open
Abstract
This review focuses on the biology of ocular adnexal marginal zone B-cell lymphomas of the mucosa-associated lymphatic tissue (MALT) (OAMZL) subtype. The ocular adnexa includes all structures and tissues within the orbit except for the eye bulb. In the region of the ocular adnexa, MALT lymphomas represent the most common subtype of lymphoma, accounting for around 8% of all non-Hodgkin lymphomas. These lymphomas are often preceded by inflammatory precursor lesions. Either autoantigens or infectious antigens may lead to disease development by functioning as continuous antigenic triggers. This triggering leads to a constitutive activation of the NF-κB signaling pathway. The role of antigenic stimulation in the pathogenesis of OAMZL is supported by the detection of somatic mutations (partially with further intraclonal diversity) in their rearranged immunoglobulin V genes; hence, their derivation from germinal-center-experienced B cells, by a restricted IGHV gene usage, and the validation of autoreactivity of the antibodies in selected cases. In the established lymphomas, NF-κB activity is further enforced by mutations in various genes regulating NF-κB activity (e.g., TNFAIP3, MYD88), as well as recurrent chromosomal translocations affecting NF-κB pathway components in a subset of cases. Further pathogenetic mechanisms include mutations in genes of the NOTCH pathway, and of epigenetic regulators. While gene expression and sequencing studies are available, the role of differential methylation of lymphoma cells, the role of micro-RNAs, and the contribution of the microenvironment remain largely unexplored.
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Affiliation(s)
- Patricia Johansson
- Institute of Cell Biology (Cancer Research), Faculty of Medicine, University of Duisburg-Essen, 45147 Essen, Germany;
| | - Anja Eckstein
- Molecular Ophthalmology Group, Department of Ophthalmology, University of Duisburg-Essen, 45147 Essen, Germany;
| | - Ralf Küppers
- Institute of Cell Biology (Cancer Research), Faculty of Medicine, University of Duisburg-Essen, 45147 Essen, Germany;
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22
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Zhang YY, Peng J, Luo XJ. Post-translational modification of MALT1 and its role in B cell- and T cell-related diseases. Biochem Pharmacol 2022; 198:114977. [PMID: 35218741 DOI: 10.1016/j.bcp.2022.114977] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Revised: 02/18/2022] [Accepted: 02/18/2022] [Indexed: 02/06/2023]
Abstract
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a multifunctional protein. MALT1 functions as an adaptor protein to assemble and recruit proteins such as B-cell lymphoma 10 (BCL10) and caspase-recruitment domain (CARD)-containing coiled-coil protein 11 (CARD11). Conversely it also acts as a paracaspase to cleave specified substrates. Because of its involvement in immunity, inflammation and cancer through its dual functions of scaffolding and catalytic activity, MALT1 is becoming a promising therapeutic target in B cell- and T cell-related diseases. There is growing evidence that the function of MALT1 is subtly modulated via post-translational modifications. This review summarized recent progress in relevant studies regarding the physiological and pathophysiological functions of MALT1, post-translational modifications of MALT1 and its role in B cell- and T cell- related diseases. In addition, the current available MALT1 inhibitors were also discussed.
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Affiliation(s)
- Yi-Yue Zhang
- Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China
| | - Jun Peng
- Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
| | - Xiu-Ju Luo
- Department of Laboratory Medicine, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
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23
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Uhl B, Prochazka KT, Fechter K, Pansy K, Greinix HT, Neumeister P, Deutsch AJA. Impact of the microenvironment on the pathogenesis of mucosa-associated lymphoid tissue lymphomas. World J Gastrointest Oncol 2022; 14:153-162. [PMID: 35116108 PMCID: PMC8790412 DOI: 10.4251/wjgo.v14.i1.153] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/16/2021] [Accepted: 12/10/2021] [Indexed: 02/06/2023] Open
Abstract
Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphomas of mucosa-associated lymphoid tissue (MALT), also known as MALT lymphomas. These arise at a wide range of different extranodal sites, with most cases affecting the stomach, the lung, the ocular adnexa and the thyroid. The small intestine is involved in a lower percentage of cases. Lymphoma growth in the early stages is associated with long-lasting chronic inflammation provoked by bacterial infections (e.g., Helicobacter pylori or Chlamydia psittaci infections) or autoimmune conditions (e.g., Sjögren’s syndrome or Hashimoto thyroiditis). While these inflammatory processes trigger lymphoma cell proliferation and/or survival, they also shape the microenvironment. Thus, activated immune cells are actively recruited to the lymphoma, resulting in either direct lymphoma cell stimulation via surface receptor interactions and/or indirect lymphoma cell stimulation via secretion of soluble factors like cytokines. In addition, chronic inflammatory conditions cause the acquisition of genetic alterations resulting in autonomous lymphoma cell growth. Recently, novel agents targeting the microenvironment have been developed and clinically tested in MALT lymphomas as well as other lymphoid malignancies. In this review, we aim to describe the composition of the microenvironment of MALT lymphoma, the interaction of activated immune cells with lymphoma cells and novel therapeutic approaches in MALT lymphomas using immunomodulatory and/or microenvironment-targeting agents.
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Affiliation(s)
- Barbara Uhl
- Division of Hematology, Medical University of Graz, Graz 8036, Austria
| | | | - Karoline Fechter
- Division of Hematology, Medical University of Graz, Graz 8036, Austria
| | - Katrin Pansy
- Division of Hematology, Medical University of Graz, Graz 8036, Austria
| | | | - Peter Neumeister
- Division of Hematology, Medical University of Graz, Graz 8036, Austria
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Chung HU, Son JH. Ocular adnexal mucosa-associated lymphoid tissue lymphoma: a narrative review. JOURNAL OF YEUNGNAM MEDICAL SCIENCE 2022; 39:3-11. [PMID: 34521183 PMCID: PMC8895963 DOI: 10.12701/yujm.2021.01263] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 08/01/2021] [Accepted: 08/12/2021] [Indexed: 12/02/2022]
Abstract
Lymphoma is the most common primary tumor of the orbit, accounting for 55% of all orbital malignancies. When divided into histopathological subtypes, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) comprises the largest proportion. Clinical manifestations are unspecific, but in patients with slow-growing painless orbital mass, or red conjunctival lesion suggestive of 'salmon patch', ocular adnexa lymphoma (OAL) should be suspected. Although the pathogenetic mechanism of ocular adnexal MALT lymphoma (OAML) is not yet fully understood, the relationship between OAML and Chlamydia psittaci has been hypothesized recently, similar to that between gastric MALT lymphoma and Helicobacter pylori. This suggests a new treatment option for OAML; bacterial eradication therapy with systemic antibiotics. Several other treatment methods for OAML have been introduced, but no treatment guidelines have been established yet. In this article, we summarize the current knowledge on the clinical features, pathogenesis, diagnostic methods, therapeutic strategies, and prognosis of OAML.
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Affiliation(s)
- Hyun Uk Chung
- Yeungnam Eye Center, Yeungnam University Hospital, Daegu, Korea
| | - Jun Hyuk Son
- Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, Korea
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25
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Eagle ZR, Essien F, Zibert K, Miller C, Van Dellen M, Eden R, Pinson R. Helicobacter pylori-negative extra-nodal marginal zone B-cell lymphoma of Mucosa-Associated Lymphoid Tissue (MALT) type following Roux-en-Y Gastric Bypass (RYGB). Clin Case Rep 2022; 10:e05261. [PMID: 35106160 PMCID: PMC8784857 DOI: 10.1002/ccr3.5261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 09/17/2021] [Accepted: 11/19/2021] [Indexed: 11/07/2022] Open
Abstract
Gastric MALT lymphoma is a common type of non-Hodgkin's lymphoma that has the potential for cure in patients found to have concomitant Helicobacter pylori (H. pylori) infection. This case report explores the evaluation, diagnosis, and treatment of H. pylori-negative MALT lymphoma in a patient with a history of a RYGB.
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Affiliation(s)
- Zachary R. Eagle
- Department of Internal MedicineKeesler Medical CenterKeesler Air Force BaseKeesler AFBMississippiUSA
| | - Francis Essien
- Department of Internal MedicineKeesler Medical CenterKeesler Air Force BaseKeesler AFBMississippiUSA
| | - Kimberly Zibert
- Division of GastroenterologyDepartment of Internal MedicineSan Antonio Medical CenterSan AntonioTexasUSA
| | - Charles Miller
- Division of GastroenterologyDepartment of Internal MedicineSan Antonio Medical CenterSan AntonioTexasUSA
| | - Melissa Van Dellen
- Division of PathologyDepartment of Internal MedicineKeesler Medical CenterKeesler Air Force BaseKeesler AFBMississippiUSA
| | - Rina Eden
- Division of PathologyDepartment of Internal MedicineKeesler Medical CenterKeesler Air Force BaseKeesler AFBMississippiUSA
| | - Ross Pinson
- Department of Internal MedicineKeesler Medical CenterKeesler Air Force BaseKeesler AFBMississippiUSA
- Division of GastroenterologyDepartment of Internal MedicineKeesler Medical CenterKeesler Air Force BaseKeesler AFBMississippiUSA
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Recent Advances in the Genetic of MALT Lymphomas. Cancers (Basel) 2021; 14:cancers14010176. [PMID: 35008340 PMCID: PMC8750177 DOI: 10.3390/cancers14010176] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 12/28/2021] [Accepted: 12/29/2021] [Indexed: 12/20/2022] Open
Abstract
Simple Summary Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common subtype of marginal zone lymphomas. These B-cell neoplasms may arise from many organs and usually have an indolent behavior. Recurrent chromosomal translocations and cytogenetic alterations are well characterized, some of them being associated to specific sites. Through next-generation sequencing technologies, the mutational landscape of MALT lymphomas has been explored and available data to date show that there are considerable variations in the incidence and spectrum of mutations among MALT lymphoma of different sites. Interestingly, most of these mutations affect several common pathways and some of them are potentially targetable. Gene expression profile and epigenetic studies have also added new information, potentially useful for diagnosis and treatment. This article provides a comprehensive review of the genetic landscape in MALT lymphomas. Abstract Mucosa-associated lymphoid tissue (MALT) lymphomas are a diverse group of lymphoid neoplasms with B-cell origin, occurring in adult patients and usually having an indolent clinical behavior. These lymphomas may arise in different anatomic locations, sharing many clinicopathological characteristics, but also having substantial variances in the aetiology and genetic alterations. Chromosomal translocations are recurrent in MALT lymphomas with different prevalence among different sites, being the 4 most common: t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). Several chromosomal numerical abnormalities have also been described, but probably represent secondary genetic events. The mutational landscape of MALT lymphomas is wide, and the most frequent mutations are: TNFAIP3, CREBBP, KMT2C, TET2, SPEN, KMT2D, LRP1B, PRDM1, EP300, TNFRSF14, NOTCH1/NOTCH2, and B2M, but many other genes may be involved. Similar to chromosomal translocations, certain mutations are enriched in specific lymphoma types. In the same line, variation in immunoglobulin gene usage is recognized among MALT lymphoma of different anatomic locations. In the last decade, several studies have analyzed the role of microRNA, transcriptomics and epigenetic alterations, further improving our knowledge about the pathogenic mechanisms in MALT lymphoma development. All these advances open the possibility of targeted directed treatment and push forward the concept of precision medicine in MALT lymphomas.
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Jiang ZZ, Zheng YY, Hou CL, Liu XT. Primary mucosal-associated lymphoid tissue extranodal marginal zone lymphoma of the bladder from an imaging perspective: A case report. World J Clin Cases 2021; 9:10024-10032. [PMID: 34877346 PMCID: PMC8610910 DOI: 10.12998/wjcc.v9.i32.10024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 08/10/2021] [Accepted: 09/19/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Mucosal-associated lymphoid tissue extranodal marginal zone (MALT) lymphoma is a low-grade tumor that rarely occurs in the urinary bladder. There is currently no consensus on the common imaging findings or most appropriate treatment in MALT lymphoma in the urinary bladder due to the limited number of reports.
CASE SUMMARY A 48-year-old woman was admitted to the hospital with a 1-year history of macroscopic hematuria. Imaging showed a large homogeneous mass with an unclear boundary and an irregular morphology in the bladder. The mass had an abundant blood supply. For further diagnosis, transurethral cystoscopic biopsy and bone marrow biopsy was performed, and the patient was finally diagnosed with primary MALT lymphoma of the bladder. R-CHOP chemotherapy was carried out. After three cycles of chemotherapy, the mass disappeared and the bladder wall thickness was only 4 mm, which indicated excellent therapeutic response to the chemotherapy. To date, the patient remains asymptomatic and she visits our hospital regularly for the completion of the remaining chemotherapy cycles.
CONCLUSION Primary MALT lymphoma of the bladder is rare, and there are certain characteristics in the ultrasonographic findings. Imaging findings play an important role in evaluating the therapeutic efficacy and are critical during long-term follow-up after therapy.
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Affiliation(s)
- Zhen-Zhen Jiang
- Department of Ultrasound, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing 312000, Zhejiang Province, China
| | - Yuan-Yuan Zheng
- Department of Ultrasound, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing 312000, Zhejiang Province, China
| | - Chuan-Ling Hou
- Department of Pathology, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing 312000, Zhejiang Province, China
| | - Xia-Tian Liu
- Department of Ultrasound, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing 312000, Zhejiang Province, China
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Raderer M, Kiesewetter B. What you always wanted to know about gastric MALT-lymphoma: a focus on recent developments. Ther Adv Med Oncol 2021; 13:17588359211033825. [PMID: 34621332 PMCID: PMC8491302 DOI: 10.1177/17588359211033825] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 07/02/2021] [Indexed: 12/17/2022] Open
Abstract
The stomach is the most common site of origin for extranodal lymphomas,
with extranodal marginal zone B-cell of the mucosa associated lymphoid
tissue (MALT-lymphoma) being the predominant subtype. MALT-lymphoma
develops in mucosa associated lymphoid structures acquired by
infection or chronic antigenic stimuli and may therefore arise in
almost any organ of the human body. In spite of histopathologic
similarities between various organs upon first glance, recent findings
suggest pronounced differences between different sites, with a variety
of features specific to gastric MALT-lymphoma. The objective of this
review is to sum up the current knowledge on pathogenesis, molecular
pathology, clinical presentation and therapeutic approaches to gastric
MALT-lymphoma with in-depth discussion of recent developments.
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Affiliation(s)
- Markus Raderer
- Division of Oncology, Internal Medicine I, Medical University of Vienna, Waehringer Guertel 18 - 20, Vienna, A 1090, Austria
| | - Barbara Kiesewetter
- Division of Oncology, Internal Medicine I, Medical University of Vienna, Vienna, Austria
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Mamgain G, Patra P, Naithani M, Nath UK. The Role of Microbiota in the Development of Cancer Tumour Cells and Lymphoma of B and T Cells. Cureus 2021; 13:e19047. [PMID: 34853760 PMCID: PMC8608681 DOI: 10.7759/cureus.19047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/25/2021] [Indexed: 11/26/2022] Open
Abstract
Human body harbours enormous numbers of microbial organisms, including bacteria, viruses, and fungi which have a momentous role in well-being and illness in humans. Immune system shelters us from pathogenic bacteria, microorganisms found in human tissues have many benefits related to the functional movement of the host by regulating important procedures such as immunity, signalling, and breakdown. Lymphocytes assume a significant part in the reaction to bacterial colonization, primarily by prompting a safe reaction to obstruction or initiation. Most immunologically occupant cells have a place with the mucosal invulnerable framework and are continually motioned by dendritic cells or other Antigen introducing cells that gather intestinal samples. Thus, Microbiome is a key contributor to developing lymphoma and specific alterations to microbiome composition could attenuate the risk. There is an indication that microbial morphology can affect and control humanoids. The difference in the composition of these microorganisms is associated with tumour development. With the increased knowledge of the connection among the human microbiome and carcinogenesis, the use of these findings to prevent, predict or diagnose of lymphomas has attracted a great attention. In this article, we explored current knowledge of various microbial ecosystems, their connection with carcinogens and the potential for useful microorganisms to control and prevent B and T cell lymphoma.
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Affiliation(s)
- Garima Mamgain
- Medical Oncology and Haematology, All India Institute of Medical Sciences, Rishikesh, IND
| | - Priyanka Patra
- Biochemistry, All India Institute of Medical Sciences, Rishikesh, IND
| | - Manisha Naithani
- Biochemistry & Advanced Center of Continuous Professional Development, All India Institute of Medical Sciences, Rishikesh, IND
| | - Uttam Kumar Nath
- Medical Oncology and Haematology, All India Institute of Medical Sciences, Rishikesh, IND
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Donzel M, Baseggio L, Fontaine J, Pesce F, Ghesquières H, Bachy E, Verney A, Traverse-Glehen A. New Insights into the Biology and Diagnosis of Splenic Marginal Zone Lymphomas. ACTA ACUST UNITED AC 2021; 28:3430-3447. [PMID: 34590593 PMCID: PMC8482189 DOI: 10.3390/curroncol28050297] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 09/02/2021] [Accepted: 09/03/2021] [Indexed: 11/16/2022]
Abstract
Splenic marginal zone lymphoma (SMZL) is a small B-cell lymphoma, which has been recognized as a distinct pathological entity since the WHO 2008 classification. It classically presents an indolent evolution, but a third of patients progress rapidly and require aggressive treatments, such as immuno-chemotherapy or splenectomy, with all associated side effects. In recent years, advances in the comprehension of SMZL physiopathology have multiplied, thanks to the arrival of new devices in the panel of available molecular biology techniques, allowing the discovery of new molecular findings. In the era of targeted therapies, an update of current knowledge is needed to guide future researches, such as those on epigenetic modifications or the microenvironment of these lymphomas.
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Affiliation(s)
- Marie Donzel
- Institut de pathologie multi-sites, Hôpital Lyon Sud, Hospices Civils de Lyon, 69310 Pierre Bénite, France; (M.D.); (J.F.); (F.P.)
| | - Lucile Baseggio
- Laboratoire d’hématologie, Hôpital Lyon Sud, Hospices Civils de Lyon, 69310 Pierre Bénite, France;
- INSERM-Unité Mixte de Recherche 1052 CNRS 5286, Team “Clinical and Experimental Models of Lymphomagenesis”, UCBL, Cancer Research Center of Lyon, Université Lyon, 69001 Lyon, France; (H.G.); (E.B.); (A.V.)
| | - Juliette Fontaine
- Institut de pathologie multi-sites, Hôpital Lyon Sud, Hospices Civils de Lyon, 69310 Pierre Bénite, France; (M.D.); (J.F.); (F.P.)
| | - Florian Pesce
- Institut de pathologie multi-sites, Hôpital Lyon Sud, Hospices Civils de Lyon, 69310 Pierre Bénite, France; (M.D.); (J.F.); (F.P.)
| | - Hervé Ghesquières
- INSERM-Unité Mixte de Recherche 1052 CNRS 5286, Team “Clinical and Experimental Models of Lymphomagenesis”, UCBL, Cancer Research Center of Lyon, Université Lyon, 69001 Lyon, France; (H.G.); (E.B.); (A.V.)
- Service d’hématologie, Hôpital Lyon Sud, Hospices Civils de Lyon, 69310 Pierre Bénite, France
| | - Emmanuel Bachy
- INSERM-Unité Mixte de Recherche 1052 CNRS 5286, Team “Clinical and Experimental Models of Lymphomagenesis”, UCBL, Cancer Research Center of Lyon, Université Lyon, 69001 Lyon, France; (H.G.); (E.B.); (A.V.)
- Service d’hématologie, Hôpital Lyon Sud, Hospices Civils de Lyon, 69310 Pierre Bénite, France
| | - Aurélie Verney
- INSERM-Unité Mixte de Recherche 1052 CNRS 5286, Team “Clinical and Experimental Models of Lymphomagenesis”, UCBL, Cancer Research Center of Lyon, Université Lyon, 69001 Lyon, France; (H.G.); (E.B.); (A.V.)
| | - Alexandra Traverse-Glehen
- Institut de pathologie multi-sites, Hôpital Lyon Sud, Hospices Civils de Lyon, 69310 Pierre Bénite, France; (M.D.); (J.F.); (F.P.)
- INSERM-Unité Mixte de Recherche 1052 CNRS 5286, Team “Clinical and Experimental Models of Lymphomagenesis”, UCBL, Cancer Research Center of Lyon, Université Lyon, 69001 Lyon, France; (H.G.); (E.B.); (A.V.)
- Correspondence: ; Tel.: +33-4-7876-1186
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Constitutive activation of NF-κB during early bone marrow development results in loss of B cells at the pro-B-cell stage. Blood Adv 2021; 5:745-755. [PMID: 33560391 DOI: 10.1182/bloodadvances.2020002932] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 12/21/2020] [Indexed: 11/20/2022] Open
Abstract
There is a considerable body of work exploring the role of NF-κB family of transcription factors in the maturation and functions of later stage B cells; however, their role in the earlier bone marrow stages of development is less well understood despite the demonstration that NF-κB activity is present at all early stages of B-cell development. To explore the consequences of early, B cell-targeted constitutive activation of both NF-κB pathways on B-cell development, we generated mice that have either or both. NF-κB pathways constitutively activated beginning in early pro-B cells. In marked contrast to activating a single pathway, we found mice with both pathways constitutively activated displayed a profound loss of B cells, starting with early pro-B cells and peaking at the late pro-B-cell stage, at least in part as a result of increased apoptosis. This effect was found to be cell autonomous and to have striking phenotypic consequences on the secondary lymphoid organs and circulating antibody levels. This effect was also found to be temporal in nature as similar activation under a Cre expressed later in development did not result in generation of a similar phenotype. Taken together, these findings help to shed further light on the need for tight regulation of the NF-κB family of transcription factors during the various stages of B-cell development in the bone marrow.
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Kiesewetter B, Raderer M. How can we assess and measure prognosis for MALT lymphoma? A review of current findings and strategies. Expert Rev Hematol 2021; 14:391-399. [PMID: 33764848 DOI: 10.1080/17474086.2021.1909468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
INTRODUCTION : MALT (mucosa associated lymphoid tissue) lymphoma is a distinct type of B-cell lymphoma characterized by extranodal manifestation and an indolent clinical course with 10-year survival rates up to 90%. However, transformation to aggressive lymphoma may occur and treatment is indicated in case of symptomatic or progressive disease. AREAS COVERED : This review covers clinical and biological features potentially related to prognosis and outcome of MALT lymphoma patients, as well as available prognostic tools and risk stratification systems with a focus on the MALT-IPI (international prognostic index) and the POD24 (progression of disease at 24 months) cohort. In addition, we address the role of watch-and-wait, the importance of defining the optimal time point for treatment initiation and the relevance of depth of remission, which appear to be some of the central questions for physicians involved in the care of MALT lymphoma patients. A computerized database search using PubMed® was performed to identify available publications on prognostic factors and risk stratification tools in MALT lymphoma. EXPERT OPINION : Despite the development of disease-specific risk stratification systems, there is no clear concept how to measure prognosis and tailor treatment. Careful observation of the individual clinical course is essential to assess the optimal time point of treatment initiation and avoid overtreatment, particularly in patients with disseminated disease. In addition, early detection of patients with histological transformation is necessary, as these patients face a poor prognosis.
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Affiliation(s)
- Barbara Kiesewetter
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - Markus Raderer
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
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Case report of primary dural lymphoma mimicking a cerebellar meningioma and brief review of literature. Acta Neurol Belg 2021; 121:409-414. [PMID: 31301042 DOI: 10.1007/s13760-019-01188-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 07/02/2019] [Indexed: 10/26/2022]
Abstract
Primary dural lymphoma (PDL) is an extremely rare subtype of primary central nervous system lymphoma arising from the dura mater in absence of systemic disease. The most common histological type is the low-grade marginal zone lymphoma, whereas high-grade lymphomas are unusual. We present a case of primary diffuse large B-cell lymphoma, presenting as PDL in the posterior fossa, originating from the dura mater of the petrous bone covering the surface of the left cerebellum, a location not previously described. A 65-year-old woman presented with sudden onset of severe dizziness was admitted in otolaryngology department then transferred to neurosurgery ward. CT scan revealed a large lesion involving left cerebellum, subsequent MRI of the brain demonstrated an enhancing mass suggestive for petrous bone meningioma. The tumor was excised, and the histopathological examination unexpectedly revealed a diffuse large B-cell lymphoma. The patient received postoperative chemoradiotherapy. 20 months after surgery a good outcome was registered. Due to the rarity of primary dural lymphomas no standard treatment is available, however, gross total or subtotal resection followed by adjuvant therapy seems to be a good choice to manage the pathology.
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Zhang C, Xia R, Gu T, Wang L, Tian Z, Zhu L, Han J, Hu Y, Wang Y, Sun J, Li J. Clinicopathological aspects of primary mucosa-associated lymphoid tissue lymphoma of the salivary gland: A retrospective single-center analysis of 72 cases. J Oral Pathol Med 2021; 50:723-730. [PMID: 33730431 DOI: 10.1111/jop.13168] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 01/27/2021] [Accepted: 02/23/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Salivary gland extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) is uncommon and has not been studied extensively. We aimed to investigate the features of clinicopathological and molecular changes of salivary MALT lymphoma. METHODS Seventy-two cases of primary salivary MALT lymphoma that had clinicopathological information available were utilized in this study. MALT1 gene translocation, trisomy 3, and trisomy 18 were detected by interphase fluorescence in situ hybridization (FISH). The data were analyzed using SPSS 17.0 software package. RESULTS The ratio of male to female was 1:2.8, and the median age was 57.0 years. 12.5% (9/72) of the patients presented with multiple swellings. Among the others with solitary mass, the parotid gland was involved most frequently (47/63,74.6%), followed by the palate (7/63, 11.1%). 34.7% of patients had an autoimmune disease, with Sjögren syndrome (SS) being the most common. Among the 70 cases successfully performed, it was identified that trisomy 3 was the most frequent molecular change (41/70, 58.6%), followed by trisomy 18 (7/70, 10%) and MALT1 translocation (5/70, 7.1%). The tumor tissue tended to exhibit trisomy 3 in patients without SS (p = 0.038). The 5-year overall survival was 94.1%, and the 5-year disease-free survival was 85.3% (mean follow-up time: 104.7 months). The patients without SS and trisomy 18 had a prolonged recurrence-free survival (p = 0.015, p = 0.001 respectively). CONCLUSION Salivary gland MALT lymphoma is associated with autoimmune diseases, and trisomy 3 is the most common genetic change. Trisomy 18 can be used to predict the possibility of tumor relapse.
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Affiliation(s)
- Chunye Zhang
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Department of Oral Pathology, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, Shanghai Ninth People's Hospital, Shanghai, China
| | - Ronghui Xia
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Department of Oral Pathology, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, Shanghai Ninth People's Hospital, Shanghai, China
| | - Ting Gu
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Department of Oral Pathology, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, Shanghai Ninth People's Hospital, Shanghai, China
| | - Lizhen Wang
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Department of Oral Pathology, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, Shanghai Ninth People's Hospital, Shanghai, China
| | - Zhen Tian
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Department of Oral Pathology, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, Shanghai Ninth People's Hospital, Shanghai, China
| | - Ling Zhu
- Department of Radiology, Shanghai Ninth People's Hospital, Shanghai, China
| | - Jing Han
- Department of Oral and Maxillofacial-Head and Neck Oncology, College of Stomatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuhua Hu
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Department of Oral Pathology, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, Shanghai Ninth People's Hospital, Shanghai, China
| | - Yu Wang
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Department of Oral Pathology, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, Shanghai Ninth People's Hospital, Shanghai, China
| | - Jingjing Sun
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Department of Oral Pathology, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, Shanghai Ninth People's Hospital, Shanghai, China
| | - Jiang Li
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Department of Oral Pathology, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, Shanghai Ninth People's Hospital, Shanghai, China
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Liang X, Cao Y, Li C, Yu H, Yang C, Liu H. MALT1 as a promising target to treat lymphoma and other diseases related to MALT1 anomalies. Med Res Rev 2021; 41:2388-2422. [PMID: 33763890 DOI: 10.1002/med.21799] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 12/23/2020] [Accepted: 03/03/2021] [Indexed: 12/25/2022]
Abstract
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a key adaptor protein that regulates the NF-κB pathway, in which MALT1 functions as a scaffold protein and protease to trigger downstream signals. The abnormal expression of MALT1 is closely associated with lymphomagenesis and other diseases, including solid tumors and autoimmune diseases. MALT1 is the only protease in the underlying pathogenesis of these diseases, and its proteolytic activity can be pharmacologically regulated. Therefore, MALT1 is a potential and promising target for anti-lymphoma and other MALT1-related disease treatments. Currently, the development of MALT1 inhibitors is still in its early stages. This review presents an overview of MALT1, particularly its X-ray structures and biological functions, and elaborates on the pathogenesis of diseases associated with its dysregulation. We then summarize previously reported MALT1 inhibitors, focusing on their molecular structure, biological activity, structure-activity relationship, and limitations. Finally, we propose future research directions to accelerate the discovery of novel MALT1 inhibitors with clinical applications. Overall, this review provides a comprehensive and systematic overview of MALT1-related research advances and serves as a theoretical basis for drug discovery and research.
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Affiliation(s)
- Xuewu Liang
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - YiChun Cao
- School of Pharmacy, Fudan University, Shanghai, China
| | - Chunpu Li
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
| | - Haolan Yu
- Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Chenghua Yang
- Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Hong Liu
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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Yokoyama T, Tanaka T, Harada S, Ueda T, Ejiri G, Sasaki S, Takeda M, Yoshimura A. A case of gastric and duodenal mucosa-associated lymphoid tissue lymphoma with multiple gastric cancers: a case report. Surg Case Rep 2021; 7:30. [PMID: 33492581 PMCID: PMC7835272 DOI: 10.1186/s40792-020-01081-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 11/24/2020] [Indexed: 12/02/2022] Open
Abstract
Background Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is often caused by Helicobacter pylori and has a good prognosis. Rarely, patients with MALT lymphoma may have gastric cancer and have a poor prognosis. Case presentation We herein report a case in which surgical treatment was achieved for a 72-year-old male patient with gastric and duodenal MALT lymphoma coexisting multiple gastric cancers. He underwent upper endoscopy for epigastric discomfort, which revealed mucosal erosion on the posterior wall of the middle body of the stomach, an elevated lesion on the duodenal bulb, and a raised tumor on the antrum of the stomach. He was diagnosed with gastric and duodenal MALT lymphoma with early gastric cancer. One month after H. pylori eradication, a second upper endoscopy revealed no improvement in the gastric or duodenal mucosa, and areas of strong redness with a shallow recess just below the cardia of the stomach. As a result, a diagnosis of gastric and duodenal MALT lymphoma with two gastric cancers was made. Total gastrectomy with proximal duodenum resection using intraoperative upper endoscopy and regional lymph node dissection was performed. Pathologically, gastric and duodenal MALT lymphoma and three gastric cancers were detected. Since one of them was an advanced cancer, he started taking S-1 after his general condition improved. Conclusion For early detection of gastric and duodenal MALT lymphoma or gastric cancer, appropriate upper endoscopy and a biopsy are important. It is necessary to select a suitable treatment, such as H. pylori eradication, endoscopic treatment, surgery, chemotherapy, and irradiation, according to the disease state.
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Affiliation(s)
- Takashi Yokoyama
- Department of Surgery, Minami-Nara General Medical Center, 8-1 Fukugami, Oyodo, Yoshino, Nara, 638-8551, Japan.
| | - Tetsuya Tanaka
- Department of Surgery, Minami-Nara General Medical Center, 8-1 Fukugami, Oyodo, Yoshino, Nara, 638-8551, Japan
| | - Suzuka Harada
- Department of Surgery, Minami-Nara General Medical Center, 8-1 Fukugami, Oyodo, Yoshino, Nara, 638-8551, Japan
| | - Takeshi Ueda
- Department of Surgery, Minami-Nara General Medical Center, 8-1 Fukugami, Oyodo, Yoshino, Nara, 638-8551, Japan
| | - Goki Ejiri
- Department of Surgery, Minami-Nara General Medical Center, 8-1 Fukugami, Oyodo, Yoshino, Nara, 638-8551, Japan
| | - Shoh Sasaki
- Department of Pathology, Nara Medical University Hospital, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan
| | - Maiko Takeda
- Department of Pathology, Nara Medical University Hospital, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan
| | - Atsushi Yoshimura
- Department of Surgery, Minami-Nara General Medical Center, 8-1 Fukugami, Oyodo, Yoshino, Nara, 638-8551, Japan
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Li JJ, Chen BC, Dong J, Chen Y, Chen YW. Synchronous colonic mucosa-associated lymphoid tissue lymphoma found after surgery for adenocarcinoma: A case report and review of literature. World J Clin Cases 2020; 8:6456-6464. [PMID: 33392331 PMCID: PMC7760443 DOI: 10.12998/wjcc.v8.i24.6456] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 10/11/2020] [Accepted: 10/26/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Mucosa-associated lymphoid tissue (MALT) lymphoma is a subtype of non-Hodgkin lymphoma that is mainly involved in the gastrointestinal tract. The synchronous occurrence of colonic MALT lymphoma and adenocarcinoma in the same patient is extremely rare. We here report a case of synchronous colonic MALT lymphoma found on surveillance colonoscopy five months after surgery and chemotherapy for sigmoid adenocarcinoma. CASE SUMMARY A 67-year-old man was admitted because of hematochezia for two months. Colonoscopy suggested a colonic tumor before hospitalization. Abdominal computed tomography (CT) revealed local thickening of the sigmoid colon. The patient underwent a left hemicolectomy with local lymph node dissection. The histopathology revealed moderately differentiated adenocarcinoma and partially mucinous adenocarcinoma. The pTNM stage was T3N1Mx. The patient received chemotherapy with six cycles of mFOLFOX6 after surgery. Colonoscopy was performed five months later and revealed single, flat, polypoid lesions of the colon 33 cm away from the anus. Subsequently, the patient underwent endoscopic mucosal resection for further diagnosis. The pathological diagnosis was MALT lymphoma. Positron emission tomography /CT suggested metastasis. The patient refused further treatment and died ten months later. CONCLUSION Colonic MALT lymphoma may occur after surgery and chemotherapy for adenocarcinoma as a synchronous malignancy. Regular surveillance colonoscopy and careful monitoring after surgery are critical.
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Affiliation(s)
- Juan-Juan Li
- Department of Intensive Care Unit and Comprehensive Support, Wang-Jiang-Shan Branch of Zhejiang Provincial People's Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
| | - Bing-Chen Chen
- Department of Colorectal Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
| | - Jie Dong
- Department of Gastroenterology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
| | - Yuan Chen
- Department of Pathology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
| | - You-Wei Chen
- Department of Gastroenterology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
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Epstein-Barr Virus-negative Marginal Zone Lymphoma as an Uncommon Form of Monomorphic Posttransplant Lymphoproliferative Disorder. Am J Surg Pathol 2020; 44:1340-1352. [PMID: 32554995 DOI: 10.1097/pas.0000000000001514] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Monomorphic posttransplant lymphoproliferative disorders have been defined as lymphoid or plasmacytic proliferations that fulfill criteria for one of the B-cell or T/NK-cell neoplasms recognized in immunocompetent hosts in the current WHO Classification. Low-grade B-cell neoplasms have historically been excluded from this category, although rare reports of marginal zone lymphoma (MZL) have been described. We report 9 cases of posttransplant Epstein-Barr virus-negative MZL, all arising in solid organ transplant recipients (4 renal, 3 liver, 1 cardiac, and 1 liver, pancreas, and small bowel). Seven were extranodal MZL of mucosa-associated lymphoid tissue type, all of which had gastrointestinal involvement (4 colon, 1 duodenum, 1 stomach, and 1 oropharynx/base of tongue). Notably, the preferential involvement of intestine distinguishes posttransplant extranodal MZL from sporadic cases. Immunoglobulin light-chain restriction was seen in all cases, with polymerase chain reaction showing a monoclonal pattern in 7 of 8 cases with successful amplification of polymerase chain reaction products. A clonally unrelated recurrence was seen in one case. Next-generation sequencing identified recurrent mutations previously reported in MZL in 3/5 cases. MZL was diagnosed at least 1 year after solid organ transplant (median time to presentation, 84 mo; range, 13 to 108 mo). The median age was 44 (range, 9 to 73 y); the male: female ratio was 5:4. The mean follow-up was 33.4 months, with an indolent clinical course observed. A subset responded to reduction in immunosuppression and anti-CD20 therapy alone. These data support the designation of Epstein-Barr virus-negative MZL as an uncommon form of monomorphic posttransplant lymphoproliferative disorders.
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First Line Systemic Treatment for MALT Lymphoma-Do We Still Need Chemotherapy? Real World Data from the Medical University Vienna. Cancers (Basel) 2020; 12:cancers12123533. [PMID: 33256131 PMCID: PMC7761357 DOI: 10.3390/cancers12123533] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 11/23/2020] [Accepted: 11/25/2020] [Indexed: 12/23/2022] Open
Abstract
There is no clear therapeutic algorithm for mucosa-associated lymphoid tissue (MALT) lymphoma beyond Helicobacter pylori eradication and while chemotherapy-based regimens are standard for MALT lymphoma patients in need of systemic treatment, it appears of interest to also investigate chemotherapy-free strategies. We have retrospectively assessed MALT lymphoma patients undergoing upfront systemic treatment, classified either as chemotherapy (=classical cytostatic agents +/- rituximab) or immunotherapy (=immunomodulatory agents or single anti-CD20 antibodies) at the Medical University Vienna 1999-2019. The primary endpoint was progression-free survival (PFS). In total, 159 patients were identified with a median follow-up of 67 months. The majority of patients had extragastric disease (80%), but we also identified 32 patients (20%) with Helicobacter pylori negative or disseminated gastric lymphoma. Regarding the type of first line treatment and outcome, 46% (74/159) received a chemotherapy-based regimen and 54% (85/159) immunotherapy including IMiDs lenalidomide/thalidomide (37%), anti-CD20-anitbodies rituximab/ofatumumab (27%), macrolides clarithromycin/azithromycin (27%) and proteasome inhibitor bortezomib (9%). Median PFS was 76 months (95%CI 50-102), and while the overall response (90% vs. 68%, p < 0.01) and the complete remission rate (75% vs. 43%, p < 0.01) was significantly higher for chemotherapy, there was no difference in PFS between chemotherapy (median 81 months, 95%CI 47-116) and immunotherapy (76 months, 95%CI 50-103, p = 0.57), suggesting comparable long-term outcomes. To conclude, our data show higher response rates with chemo- compared to immunotherapy, but this did not translate into a superior PFS. Given the biological background of MALT lymphoma, and the favorable toxicity profile of novel immunomodulatory treatments, this should be further investigated.
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Ismail S, Kherbek H, Skef J, Naser Eldine M, Alshehabi Z. Primary marginal zone lymphoma of the breast; a rare case report and review of the literature. HUMAN PATHOLOGY: CASE REPORTS 2020; 22:200443. [DOI: 10.1016/j.ehpc.2020.200443] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
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Huh SJ, Oh SY, Lee S, Lee JH, Kim SH, Pak MK, Kim HJ. Mutational analysis of extranodal marginal zone lymphoma using next generation sequencing. Oncol Lett 2020; 20:205. [PMID: 32963611 PMCID: PMC7491050 DOI: 10.3892/ol.2020.12068] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Accepted: 07/06/2020] [Indexed: 12/16/2022] Open
Abstract
Extranodal marginal zone lymphoma is a type of low-grade B-cell lymphoma that can be classified as a mucosal-associated lymphoid tissue (MALT) lymphoma. Recently, second-generation or next-generation sequencing (NGS), which allows simultaneous sequencing of hundreds to billions of DNA strands, has been a focus of attention and is rapidly being adopted in various fields. In the present study, paraffin-embedded tissue samples of gastric MALT lymphoma (n=1) and small intestine MALT lymphoma (n=4) were selected, and DNA was extracted from the tissue samples. After performing quality control, NGS was performed using HemaSCAN™, a custom panel of 426 genes, including essential blood cancer genes. NGS revealed single nucleotide variations (SNVs), short insertions and deletions (InDels) and copy number variations (CNVs). These genomic variants were reported as annotated, known or novel variants. An annotated variant, an erb-b2 receptor tyrosine kinase 2 gene amplification, was observed in one patient. Known and novel variants, including SNVs of SET binding protein 6 (SETBP6), Runt-related transcription factor 1 and Kelch-like ECH-associated protein 1 genes, InDel of the marker of proliferation Ki-67 gene, and CNVs of the zinc finger protein 703 and NOTCH1 genes, were observed in ≥2 patients. Additionally, InDels with frameshift mutations were identified in the B-cell lymphoma/leukemia 10, DEAD-box helicase 3 X-linked, forkhead box O3 and mucin 2, oligomeric mucus/gel-forming genes in one patient. Since few NGS studies have been performed on MALT lymphoma, the current results were unable to determine if the different mutations that were identified are ‘actionable’ (that is, potentially responsive to a targeted therapy) Further studies are required to determine the associations between genetic mutations and the development of MALT lymphoma.
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Affiliation(s)
- Seok Jae Huh
- Department of Internal Medicine, Dong-A University College of Medicine, Seo-gu, Busan 49201, Republic of Korea
| | - Sung Yong Oh
- Department of Internal Medicine, Dong-A University College of Medicine, Seo-gu, Busan 49201, Republic of Korea
| | - Suee Lee
- Department of Internal Medicine, Dong-A University College of Medicine, Seo-gu, Busan 49201, Republic of Korea
| | - Ji Hyun Lee
- Department of Internal Medicine, Dong-A University College of Medicine, Seo-gu, Busan 49201, Republic of Korea
| | - Sung Hyun Kim
- Department of Internal Medicine, Dong-A University College of Medicine, Seo-gu, Busan 49201, Republic of Korea
| | - Min Kyung Pak
- Department of Pathology, Dong-A University College of Medicine, Seo-gu, Busan 49201, Republic of Korea
| | - Hyo-Jin Kim
- Department of Internal Medicine, Dong-A University College of Medicine, Seo-gu, Busan 49201, Republic of Korea
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Yoo RE, Park SW, Rhim JH, Kim JE, Kim SC, Choe JY, Choung HK, Khwarg SI, Kim JH, Lee JH, Lee BE, Kang Y. CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease: multi-institutional case series. Int J Ophthalmol 2020; 13:1231-1237. [PMID: 32821676 DOI: 10.18240/ijo.2020.08.08] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 02/12/2020] [Indexed: 12/14/2022] Open
Abstract
AIM To report CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease (IgG4-MALT lymphoma), a rare but clinically important complication of ocular adnexal IgG4-related disease. METHODS We retrospectively reviewed all cases of histologically confirmed ocular adnexal IgG4-related disease at three tertiary and one secondary referral centers, between February 2003 and December 2016. Seven cases of histopathologically diagnosed IgG4-MALT lymphoma were identified. CT and MR images were analyzed by consensus of two experienced head and neck radiologists. RESULTS Lacrimal glands were the main site of involvement in all seven patients. The lesions typically showed well-demarcated margins, iso- to hyperattenuation on precontrast CT, T2 hypo- to isointensity, T1 isointensity, and homogenous internal architecture with homogenous enhancement pattern. Lesions were mostly hyperdense and isointense to normal extraocular muscles on postcontrast CT and MR images, respectively. CONCLUSION Unlike in typical ocular adnexal IgG4-related disease, T2 isointensity and hyperattenuation on precontrast CT images were noted in some IgG4-MALT lymphoma cases. Although the findings may be nonspecific, the possibility of accompanying MALT lymphoma may need to be considered, when ocular adnexal lesions in patients clinically suspected of having IgG4-related disease are refractory to glucocorticoids and show T2 isointensity and hyperattenuation on precontrast CT for the optimal management of the patients. However, this is a case series of a very rare complication of ocular adnexal IgG4-related disease, and thus caution is warranted to generalize the conclusion.
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Affiliation(s)
- Roh-Eul Yoo
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.,Department of Radiology, Seoul National University Hospital, Seoul 03080, Republic of Korea
| | - Sun-Won Park
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.,Department of Radiology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul 07061, Republic of Korea
| | - Jung Hyo Rhim
- Department of Radiology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul 07061, Republic of Korea
| | - Ji Eun Kim
- Department of Pathology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul 07061, Republic of Korea.,Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Soo Chin Kim
- Department of Radiology, Asan Medical Center, Seoul 05505, Republic of Korea
| | - Ji-Young Choe
- Department of Pathology, Hallym University Sacred Heart Hospital, Anyang 14068, Republic of Korea
| | - Ho-Kyung Choung
- Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul 07061, Republic of Korea.,Department of Ophthalmology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Sang In Khwarg
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
| | - Ji-Hoon Kim
- Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.,Department of Radiology, Seoul National University Hospital, Seoul 03080, Republic of Korea
| | - Jeong Hyun Lee
- Department of Radiology, Asan Medical Center, Seoul 05505, Republic of Korea.,Department of Radiology, Ulsan University College of Medicine, Seoul 05505, Republic of Korea
| | - Bo Eun Lee
- Department of Radiology, Asan Medical Center, Seoul 05505, Republic of Korea.,Department of Radiology, Ulsan University College of Medicine, Seoul 05505, Republic of Korea
| | - Yeonah Kang
- Department of Radiology, Inje University Haeundae Paik Hospital, Busan 47392, Republic of Korea
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Kiesewetter B, Raderer M. Immunomodulatory treatment for mucosa-associated lymphoid tissue lymphoma (MALT lymphoma). Hematol Oncol 2020; 38:417-424. [PMID: 32469432 DOI: 10.1002/hon.2754] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 05/09/2020] [Accepted: 05/25/2020] [Indexed: 12/12/2022]
Abstract
The pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma has been characterized as a dynamic process driven by lymphoma cell dependency on T-cell signaling, chronic antigenic stimulation of marginal zone B-cells and activation of the nuclear factor-kappa B signaling pathway. This concept is underlined by the strong causal connection of chronic Helicobacter pylori associated gastritis and MALT lymphoma development based on perpetual auto-antigenic stimulation of Helicobacter pylori-specific T-cells, but also its association with further potential infectious triggers and autoimmune disorders for extragastric lymphoma sites. Thus, given the dependency of MALT lymphoma cells on the tumor microenvironment, this specific entity appears highly suitable for immunomodulatory treatment strategies. Several approaches have been assessed in the last years including promising data on immunomodulatory agents "IMiDs" thalidomide and lenalidomide, macrolide antibiotics and antibodies. The aim of the present review is to discuss rationales for immunomodulatory therapies in MALT lymphoma and to present the statu quo on immunomodulatory and therefore chemotherapy-free treatment strategies for these patients.
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Affiliation(s)
- Barbara Kiesewetter
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - Markus Raderer
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
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44
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Lu HY, Biggs CM, Blanchard-Rohner G, Fung SY, Sharma M, Turvey SE. Germline CBM-opathies: From immunodeficiency to atopy. J Allergy Clin Immunol 2020; 143:1661-1673. [PMID: 31060714 DOI: 10.1016/j.jaci.2019.03.009] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Revised: 03/09/2019] [Accepted: 03/15/2019] [Indexed: 12/31/2022]
Abstract
Caspase recruitment domain (CARD) protein-B cell CLL/lymphoma 10 (BCL10)-MALT1 paracaspase (MALT1) [CBM] complexes are critical signaling adaptors that facilitate immune and inflammatory responses downstream of both cell surface and intracellular receptors. Germline mutations that alter the function of members of this complex (termed CBM-opathies) cause a broad array of clinical phenotypes, ranging from profound combined immunodeficiency to B-cell lymphocytosis. With an increasing number of patients being described in recent years, the clinical spectrum of diseases associated with CBM-opathies is rapidly expanding and becoming unexpectedly heterogeneous. Here we review major discoveries that have shaped our understanding of CBM complex biology, and we provide an overview of the clinical presentation, diagnostic approach, and treatment options for those carrying germline mutations affecting CARD9, CARD11, CARD14, BCL10, and MALT1.
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Affiliation(s)
- Henry Y Lu
- Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada; Experimental Medicine Program, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Catherine M Biggs
- Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada; Experimental Medicine Program, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Geraldine Blanchard-Rohner
- Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
| | - Shan-Yu Fung
- Department of Immunology, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University, Tianjin, China
| | - Mehul Sharma
- Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
| | - Stuart E Turvey
- Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada; Experimental Medicine Program, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
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45
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Melenotte C, Mezouar S, Mège JL, Gorvel JP, Kroemer G, Raoult D. Bacterial infection and non-Hodgkin's lymphoma. Crit Rev Microbiol 2020; 46:270-287. [PMID: 32412856 DOI: 10.1080/1040841x.2020.1760786] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
One quarter of all cancers are linked to infectious diseases. The link between viral infection and cancer has been widely studied, but few reports have focused on the carcinogenic role of bacterial infection. Nonetheless, Helicobacter pylori, Chlamydia psittaci, Coxiella burnetii, Borrelia burgdorferi and Campylobacter jejuni are bacteria that can be associated with non-Hodgkin's lymphoma (NHL), the most common haematologic malignancy. Here, we review the evidence in favour of a link between these bacterial infections and NHL. Sero-epidemiological observation makes it possible to identify a link between H. pylori, C. burnetii, B. burgdorferi infection and NHL. Helicobacter pylori, Chlamydia psittaci, Coxiella burnetii, Borrelia burgdorferi and Campylobacter jejuni could be identified in NHL tissue samples at the site of chronic inflammation, where B and T lymphocytes are attracted to participate in follicle formation. Lymphoma remissions have been observed under antimicrobial therapies supporting the carcinogenic contribution of bacteria. If the theory of causality is characterized by the lack of universal criteria for establishing a causal link between two diseases, infection and lymphoma, epidemiological, clinical, and histological evidences reported here, should lead clinicians to pay attention to these infectious agents, to detect early lymphoma transformation.
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Affiliation(s)
- Cléa Melenotte
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Soraya Mezouar
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | - Jean-Louis Mège
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
| | | | - Guido Kroemer
- Cell Biology and Metabolomics platforms, Villejuif, France.,INSERM, Paris, France.,Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.,Sorbonne Paris Cité, Université Paris Descartes, Paris, France.,Université Pierre et Marie Curie, Paris, France.,Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.,Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden
| | - Didier Raoult
- Aix-Marseille University, IRD, APHM, MEPHI, Marseille, France.,IHU-Méditerranée Infection, Marseille, France
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Izumi K, Nishikori M, Yuan H, Otsuka Y, Nakao K, Takaori-Kondo A. Establishment and characterization of a MALT lymphoma cell line carrying an API2-MALT1 translocation. Genes Chromosomes Cancer 2020; 59:517-524. [PMID: 32348592 DOI: 10.1002/gcc.22855] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 04/21/2020] [Accepted: 04/23/2020] [Indexed: 11/07/2022] Open
Abstract
MALT lymphomas with API2(BIRC3)-MALT1 translocation usually have an indolent clinical course and rarely transform into aggressive lymphoma, and there have been no lymphoma cell lines carrying API2-MALT1 translocation reported to date. We established a novel lymphoma cell line named BMA19, carrying the API2-MALT1 translocation from a patient with histologic transformation of intestinal MALT lymphoma. The cells were suggested to carry API2-MALT1 and MYC-IGH translocations by chromosomal analysis, and these translocations were confirmed by polymerase chain reaction analysis. The expression of MYC was shown to be enhanced as a result of the MYC-IGH translocation, and it is considered to have played a role in the histologic transformation of MALT lymphoma. Whole exome sequencing of BMA19 identified several nucleotide variations in genes reported to be mutated in previous studies of marginal zone lymphomas. The MALT1 inhibitor MI-2 specifically decreased cell growth, and the BMA19 cell line was suggested to be still dependent on the API2-MALT1 signal. Subtractive microarray analysis showed that one of the earliest events resulting from MALT1 inhibition is increased susceptibility to endoplasmic reticulum stress-induced apoptosis. The BMA19 cell line is considered to conserve the biological properties of MALT lymphoma and is expected to be a valuable tool for research into the pathogenesis of MALT lymphoma with an API2-MALT1 translocation.
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Affiliation(s)
- Kiyotaka Izumi
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Momoko Nishikori
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hepei Yuan
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yasuyuki Otsuka
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kensuke Nakao
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Akifumi Takaori-Kondo
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Marguet F, Fontanilles M, Bohers E, Derrey S, Langlois O, Veresezan L, Leprêtre S, Sabourin JC, Jardin F, Laquerrière A. [Low-grade dural extranodal marginal zone lymphoma]. Ann Pathol 2020; 40:243-247. [PMID: 31948699 DOI: 10.1016/j.annpat.2019.12.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Revised: 09/11/2019] [Accepted: 12/19/2019] [Indexed: 11/17/2022]
Abstract
Primary low-grade dural marginal zone lymphoma is an indolent low grade lymphoma occurring especially among middle-aged immunocompetent women, and is not associated to an infectious process, contrary to gastric or intestinal marginal zone lymphomas. Dural location is rare since only 105 cases have been reported so far. We report herein on two additional cases, a 72-year-old woman and a 36-year-old man whose lymphoma was revealed by partial seizures and headaches. Morphological analysis of surgical specimens displayed a tumoral proliferation made of small lymphocytes arranged in sheets or in nodules with CD20, CD79a and BCL2-immunopositivity, but CD5 and CD10 negativity. Molecular analysis using a panel of 34 genes involved in lymphomagenesis disclosed a deletion of SOCS1 and TNFAIP3 genes, implicated in the JAK/STAT and NFκB pathways respectively in the first patient that could explain unfavourable prognosis despite complementary radiotherapy. No anomaly was identified in the second patient who is alive with no recurrence or progression seven years after the diagnosis. Currently, there are no standardized treatment schedules, but the vast majority of patients are treated by surgery, then radiotherapy followed by adjuvant chemotherapy using methotrexate alone or in combination with rituximab. Literature review indicates that five-year survival has been estimated at 96.7%, suggesting a better prognosis compared to other locations.
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Affiliation(s)
- Florent Marguet
- Inserm U1245, service d'anatomie pathologique, UNIROUEN, Normandie Université, CHU de Rouen, 76000 Rouen, France.
| | - Maxime Fontanilles
- Inserm U1245, IRON group, service d'oncologie médicale, Centre Henri-Becquerel, UNIROUEN, Normandie Université, 76000 Rouen, France
| | - Elodie Bohers
- Inserm U1245, Centre Henri-Becquerel, UNIROUEN, Normandie Université, 76000 Rouen, France
| | - Stéphane Derrey
- Inserm U1239, service de neurochirurgie, UNIROUEN, Normandie Université, CHU de Rouen, 76000 Rouen, France
| | - Olivier Langlois
- Inserm U1239, service de neurochirurgie, UNIROUEN, Normandie Université, CHU de Rouen, 76000 Rouen, France
| | - Liana Veresezan
- Service d'anatomie pathologique, Centre Henri-Becquerel, UNIROUEN, Normandie Université, 76000 Rouen, France
| | - Stéphane Leprêtre
- Inserm U1245, service d'hématologie, Centre Henri-Becquerel, UNIROUEN, Normandie Université, 76000 Rouen, France
| | - Jean-Christophe Sabourin
- Inserm U1245, service d'anatomie pathologique, UNIROUEN, Normandie Université, CHU de Rouen, 76000 Rouen, France
| | - Fabrice Jardin
- Inserm U1245, service d'hématologie, Centre Henri-Becquerel, UNIROUEN, Normandie Université, 76000 Rouen, France
| | - Annie Laquerrière
- Inserm U1245, service d'anatomie pathologique, UNIROUEN, Normandie Université, CHU de Rouen, 76000 Rouen, France
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Abuderman AWA, Syed R, Mateen A, Malik A, Ola MS. Epidemiological characterization, genetic alterations of Helicobacter pylori infection in chronic gastric disorder and prognostic values of heterozygosity loss in chromosome 3p. Mol Biol Rep 2019; 46:4323-4332. [PMID: 31250359 DOI: 10.1007/s11033-019-04886-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Accepted: 05/15/2019] [Indexed: 11/30/2022]
Abstract
From the literature review, there seem to be no studies conducted on infection caused by Helicobacter pylori in patients with gastric MALT lymphoma in the KSA region. The present research is an attempt to understand the prevalence of patients infected with H. pylori in the selected region and the role of allelic imbalance of chromosome 3p regions to understand the clinical manifestations and features associated with MALT lymphomagenesis. The researcher analyzed the frequency of infection in patients from the region of Saudi Arabia by examining the data collected from hospitals and biopsy tissue samples as per the recommended protocol. The endoscopic diagnosis was performed to collect biopsy samples. Histology and AP-PCR DNA fingerprinting analyses were performed from the endoscopic gastric mucosal biopsies collected from patients with associated gastric MALT lymphoma. The existence of H. pylori was examined based on the results of gastric mucosal biopsies stained with hematoxylin-eosin (H&E) and Steiner's silver stains. MALT, MALT lymphoma tissue samples and H. pylori-positive chronic gastritis were examined for LOH at chromosome 3p24 using standard procedures and techniques. The findings of the paper revealed the H. pylori was found to be positive in 17% of the cases significantly high among the age group of 31-50 years. Patients with MALT, MALT lymphoma, and H. pylori-associated gastritis presented features such as lymphocyte accumulation, vacuolation, Peyer's patch appearance, and lymphatic follicles. H. pylori were found to appear as a dense colored accumulated mass in the gastric epithelial layer. The findings from AP-PCR generated DNA fingerprints revealed intense band including two prominent bands in MALT lymphoma. Among other loci, 3p24 was the only one locus that showed high percentages of LOH as reported earlier in all cancer-related cases. The findings of this research paper empower the fact that allelic imbalances play a vital role in the development of MALT lymphoma. However, future researches should be conducted to identify the chromosome regions of the AP-PCR generated DNA fingerprints of human gastric MALT lymphoma in order to confirm this proposition.
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Affiliation(s)
- Abdul Wahab Ali Abuderman
- Department of Basic Medical Science, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Rabbani Syed
- Department of Pharmaceutics, College of Pharmacy, King Saud University, PO Box 2457, Riyadh, 11451, Saudi Arabia.
| | - Ayesha Mateen
- Department of Clinical Laboratory Science, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Abdul Malik
- Department of Clinical Laboratory Science, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Mohammad Shamsul Ola
- Department of Biochemistry, College of Science, King Saud University, PO Box 2455, Riyadh, Saudi Arabia
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Kiesewetter B, Lamm W, Neuper O, Mayerhoefer ME, Simonitsch-Klupp I, Raderer M. Prolonged follow-up on lenalidomide-based treatment for mucosa-associated lymphoid tissue lymphoma (MALT lymphoma)-Real-world data from the Medical University of Vienna. Hematol Oncol 2019; 37:345-351. [PMID: 31283840 PMCID: PMC6899635 DOI: 10.1002/hon.2647] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 07/03/2019] [Accepted: 07/04/2019] [Indexed: 01/03/2023]
Abstract
Based on results of two pilot trials, lenalidomide (LEN) was found to be active and safe as monotherapy and showed an increased response rate of 80% in combination with rituximab (R) for patients with mucosa‐associated lymphoid tissue (MALT) lymphoma. While initial results were promising, there are currently no data on long‐term outcome, and larger international phase II/III trials on LEN for indolent lymphoma lack specific subgroup analyses. Thus, we have systematically analyzed 50 patients treated with LEN‐based therapy (LEN‐monotherapy n = 16, R‐LEN n = 34) at the Medical University of Vienna 2009 to 2019 and investigated long‐term outcome and relapse patterns. At a follow‐up of more than 5 years (median 68 months), 54% of patients are free of relapse, and estimated median progression‐free survival (PFS) was 72 months (95%CI 49‐96). There was no difference in PFS according to stage of disease, i.e. localized versus disseminated disease (P = .67) and previous systemic treatment (P = .16). Interestingly, but with the caveat of the limited number of patients included in this series, primary extragastric disease had a superior PFS compared with gastric lymphoma (P = .04) and also depth of response, i.e. complete or partial response versus stable disease was associated with significantly prolonged PFS (P = .01). We documented four patients (8%) with pronounced improvement of response during follow‐up including three patients initially rated as partial remission and finally achieving complete remission at 12 to 32 months. This highlights the potential of delayed responses to LEN treatment. Estimated overall survival at 5 years was excellent at 92%. These “real‐world” data confirm long‐term activity of LEN in MALT lymphoma.
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Affiliation(s)
- Barbara Kiesewetter
- Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - Wolfgang Lamm
- Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - Ortrun Neuper
- Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - Marius E Mayerhoefer
- Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
| | | | - Markus Raderer
- Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria
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50
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Li Z, Wang K, Hong J. Rare Multiple Lesions Arising in Small and Large Intestines. Gastroenterology 2019; 156:e1-e3. [PMID: 30612999 DOI: 10.1053/j.gastro.2018.10.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Revised: 09/28/2018] [Accepted: 10/04/2018] [Indexed: 12/02/2022]
Affiliation(s)
- Zhen Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, P.R. China
| | - Kangyu Wang
- School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, Jinan, P.R. China; Shandong Cancer Hospital and Institute, Jinan, P.R. China
| | - Jianguo Hong
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, P.R. China.
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