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Zhang Q, Yan W, Li H, Peng H. Advances in the Pathogenesis, Diagnosis, Treatment, and Prognosis of Marginal Zone Lymphoma. Curr Treat Options Oncol 2025; 26:142-155. [PMID: 39891871 DOI: 10.1007/s11864-025-01293-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/08/2025] [Indexed: 02/03/2025]
Abstract
OPINION STATEMENT The management of marginal zone lymphoma (MZL), an indolent B-cell non-Hodgkin lymphoma, requires a personalized and adaptive approach due to its clinical and prognostic heterogeneity. We believe treatment should emphasize a balanced strategy considering the subtype, disease burden, symptoms, and actionable genetic or environmental factors, such as infections or autoimmune diseases. For asymptomatic patients with low tumor burden or disseminated disease, a watch-and-wait approach remains appropriate, given MZL's indolent nature and the risks of overtreatment. Conversely, for symptomatic or high-burden cases, early intervention with chemoimmunotherapy is recommended for effective disease control. Surgery remains essential for both diagnosis and the treatment of localized disease. Incorporating molecular profiling and prognostic models, such as MZL-IPI and POD24, is crucial for decision-making and risk stratification. Testing for infectious agents like Helicobacter pylori or Hepatitis C virus should be standard practice, as eradication therapy offers a targeted, less toxic, and effective option in select patients. With ongoing advancements in understanding dysregulated signaling pathways and the tumor microenvironment, we anticipate novel targeted therapies and combination regimens will further improve outcomes. We advocate for molecular testing at diagnosis to identify actionable biomarkers, particularly for patients with refractory or relapsed disease. Finally, MZL management requires vigilant follow-up with adjustments based on evolving disease features. Treatment decisions should integrate patient preferences, clinical context, and the latest evidence to maximize survival while preserving quality of life.
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Affiliation(s)
- Qingyang Zhang
- Department of Hematology, The Second Xiangya Hospital, Central South University, No.139th Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Wenzhe Yan
- Department of Hematology, The Second Xiangya Hospital, Central South University, No.139th Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Heng Li
- Department of Hematology, The Second Xiangya Hospital, Central South University, No.139th Renmin Middle Road, Changsha, 410011, Hunan, China
| | - Hongling Peng
- Department of Hematology, The Second Xiangya Hospital, Central South University, No.139th Renmin Middle Road, Changsha, 410011, Hunan, China.
- Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, 410011, Hunan, China.
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Miyake K, Hirasawa K, Nishimura H, Tsukahara K. Rare incidence of mucosa-associated lymphoid tissue lymphoma presenting as buccal fat pad tumor: A case report. World J Clin Cases 2024; 12:6506-6512. [PMID: 39507115 PMCID: PMC11438690 DOI: 10.12998/wjcc.v12.i31.6506] [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: 05/29/2024] [Revised: 08/13/2024] [Accepted: 08/16/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND Mucosa-associated lymphoid tissue (MALT) lymphoma, a type of non-Hodgkin lymphoma, originates in the mucosal lining of body organs and internal cavities, including the nose, mouth, lungs, and digestive tract. The lymphoma develops when the body produces abnormal B lymphocytes. These lymphomas develop at the edge of the lymphoid tissue, called the marginal zone, and, hence, are classified as a type of marginal zone lymphomas. They are the most common type of marginal zone lymphomas although their occurrence is rare. To date, no previous cases of MALT lymphoma in the buccal fat pad have been reported. CASE SUMMARY We report the case of a patient who presented with a mass on the frontal cheek. Magnetic resonance imaging revealed a tumor in the buccal fat pad, and histopathological and immunohistochemical findings confirmed the diagnosis of MALT lymphoma. The patient had a history of Helicobacter pylori and hepatitis C virus infection, suggesting an association between these infective agents and MALT lymphoma. CONCLUSION Consideration of MALT lymphoma is essential in the differential diagnosis of frontal cheek masses.
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Affiliation(s)
- Keitaro Miyake
- Department of Otolaryngology, Head and Neck Surgery, Todachuo General Hospital, Toda-shi 335-0023, Saitama, Japan
| | - Kazuhiro Hirasawa
- Department of Otolaryngology, Head and Neck Surgery, Todachuo General Hospital, Toda-shi 335-0023, Saitama, Japan
| | - Haruka Nishimura
- Department of Otolaryngology, Head and Neck Surgery, Todachuo General Hospital, Toda-shi 335-0023, Saitama, Japan
| | - Kiyoaki Tsukahara
- Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University Hospital, Shinjuku-ku 160-0023, Japan
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Le Y, Zhu H, Ye C, Lin J, Wang N, Yang T. CT radiomics analysis discriminates pulmonary lesions in patients with pulmonary MALT lymphoma and non-pulmonary MALT lymphoma. Methods 2024; 224:54-62. [PMID: 38369073 DOI: 10.1016/j.ymeth.2024.02.003] [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: 09/14/2023] [Revised: 02/10/2024] [Accepted: 02/13/2024] [Indexed: 02/20/2024] Open
Abstract
PURPOSE The aim of this study is to create and validate a radiomics model based on CT scans, enabling the distinction between pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma and other pulmonary lesion causes. METHODS Patients diagnosed with primary pulmonary MALT lymphoma and lung infections at Fuzhou Pulmonary Hospital were randomly assigned to either a training group or a validation group. Meanwhile, individuals diagnosed with primary pulmonary MALT lymphoma and lung infections at Fujian Provincial Cancer Hospital were chosen as the external test group. We employed ITK-SNAP software for delineating the Region of Interest (ROI) within the images. Subsequently, we extracted radiomics features and convolutional neural networks using PyRadiomics, a component of the Onekey AI software suite. Relevant radiomic features were selected to build an intelligent diagnostic prediction model utilizing CT images, and the model's efficacy was assessed in both the validation group and the external test group. RESULTS Leveraging radiomics, ten distinct features were carefully chosen for analysis. Subsequently, this study employed the machine learning techniques of Logistic Regression (LR), Support Vector Machine (SVM), and k-Nearest Neighbors (KNN) to construct models using these ten selected radiomics features within the training groups. Among these, SVM exhibited the highest performance, achieving an accuracy of 0.868, 0.870, and 0.90 on the training, validation, and external testing groups, respectively. For LR, the accuracy was 0.837, 0.863, and 0.90 on the training, validation, and external testing groups, respectively. For KNN, the accuracy was 0.884, 0.859, and 0.790 on the training, validation, and external testing groups, respectively. CONCLUSION We established a noninvasive radiomics model utilizing CT imaging to diagnose pulmonary MALT lymphoma associated with pulmonary lesions. This model presents a promising adjunct tool to enhance diagnostic specificity for pulmonary MALT lymphoma, particularly in populations where pulmonary lesion changes may be attributed to other causes.
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Affiliation(s)
- Yuyin Le
- Department of Hematology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China; Department of Oncology Medicine, Fuzhou Pulmonary Hospital of Fujian Province, The Teaching Hospital of Fujian Medical University, 2 Hubian Rd, 350001 Fuzhou, Fujian, China
| | - Haojie Zhu
- Department of Hematology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China
| | - Chenjing Ye
- Fujian Medical University, Fuzhou, Fujian, China
| | - Jiexiang Lin
- The Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350001, China
| | - Nila Wang
- Department of Oncology Medicine, Fuzhou Pulmonary Hospital of Fujian Province, The Teaching Hospital of Fujian Medical University, 2 Hubian Rd, 350001 Fuzhou, Fujian, China
| | - Ting Yang
- Department of Hematology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China; Institute of Precision Medicine, Fujian Medical University, Fuzhou 350005, China.
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Chen D, Zhong DF, Yang Y, Chen SS, Liu D. Colonic mucosa-associated lymphoid tissue lymphoma: A case report. Front Surg 2023; 10:1178394. [PMID: 37181595 PMCID: PMC10169616 DOI: 10.3389/fsurg.2023.1178394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 03/22/2023] [Indexed: 05/16/2023] Open
Abstract
Background Mucosa-associated lymphoid tissue (MALT) lymphoma is a group of extranodal lymphomas that originate from B cells. Primary colonic MALT lymphoma is a rare disease, and there is no consensus on its endoscopic features and standard therapies. It is essential to raise awareness of colonic MALT lymphoma and choose the appropriate treatment. Case presentation In this case report, we describe a 0-IIb-type lesion that was found by electronic staining endoscopy and magnifying endoscopy. The patient underwent a definitive diagnostic ESD for diagnosis. The patient was evaluated for lymphoma after diagnostic ESD according to the Lugano 2014 evaluation criteria, which are divided into imaging remission on the basis of CT and/or magnetic resonance imaging (MRI) evaluation and metabolic remission on the basis of PET-CT evaluation. Based on the PET-CT results suggesting increased glucose metabolism in the sigmoid colon, the patient underwent additional surgical treatment. According to the pathological results of the surgery, we found that ESD could treat such lesions, which may provide a new option for colorectal MALT lymphoma. Conclusion The low incidence of colorectal MALT lymphoma, especially for 0-IIb lesions, which are difficult to detect, requires the use of electronic staining endoscopy to improve the detection rate. The combination with magnification endoscopy can improve the understanding of colorectal MALT lymphoma, which ultimately requires pathological support for diagnosis. According to our experience with the present patient case, ESD seems to be a feasible and economical choice for the treatment of massive colorectal MALT lymphoma. However, the combined application of ESD and another therapy scheme needs further clinical investigation.
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Affiliation(s)
- Dan Chen
- Department of Gastroenterology, Affiliated Jinhua Hospital of Wenzhou Medical University, Jinhua People's Hospital, Jinhua, China
| | - Ding-Fu Zhong
- Department of Gastroenterology, Affiliated Jinhua Hospital of Wenzhou Medical University, Jinhua People's Hospital, Jinhua, China
| | - Yi Yang
- Department of Gastroenterology, Affiliated Jinhua Hospital of Wenzhou Medical University, Jinhua People's Hospital, Jinhua, China
| | - Si-Shuang Chen
- Department of Pathology, Affiliated Jinhua Hospital of Wenzhou Medical University, Jinhua People's Hospital, Jinhua, China
| | - Dong Liu
- Department of Hepatobiliary and Pancreatic Gastroenterology, Affiliated Jinhua Hospital of Wenzhou Medical University, Jinhua People's Hospital, Jinhua, China
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Merli M, Rattotti S, Spina M, Re F, Motta M, Piazza F, Orsucci L, Ferreri AJ, Perbellini O, Dodero A, Vallisa D, Pulsoni A, Santoro A, Sacchi P, Zuccaro V, Chimienti E, Russo F, Visco C, Zignego AL, Marcheselli L, Passamonti F, Luminari S, Paulli M, Bruno R, Arcaini L. Direct-Acting Antivirals as Primary Treatment for Hepatitis C Virus-Associated Indolent Non-Hodgkin Lymphomas: The BArT Study of the Fondazione Italiana Linfomi. J Clin Oncol 2022; 40:4060-4070. [PMID: 35714311 PMCID: PMC9746784 DOI: 10.1200/jco.22.00668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
PURPOSE We prospectively treated patients with hepatitis C virus (HCV)-associated indolent lymphomas with genotype-appropriate direct-acting antivirals (DAAs) with the aim to evaluate virologic and hematologic outcomes. No prospective studies in this setting have been published so far. METHODS FIL_BArT is a prospective, multicenter, phase II trial that evaluated genotype-appropriate DAAs in untreated HCV-positive patients with indolent lymphomas without criteria for immediate conventional antilymphoma treatment. The primary objective was sustained virologic response, whereas the main secondary objectives were overall response rate of lymphoma and progression-free survival. RESULTS Forty patients were enrolled, including 27 with marginal zone lymphoma. Median age was 68 years. Extranodal sites were involved in 14 cases (35%). Main genotypes were 1 in 16 patients and 2 in 21 patients. All patients received genotype-guided DAAs: 17 ledipasvir/sofosbuvir, eight sofosbuvir plus ribavirin, and 15 sofosbuvir/velpatasvir. All patients achieved sustained virologic response (100%). DAAs were well tolerated, with only two grade 3-4 adverse events. Overall response rate of lymphoma was 45%, including eight patients (20%) achieving complete response and 10 (25%) partial response, whereas 16 exhibited stable disease and six progressed. With a median follow-up of 37 months, two patients died (3-year overall survival 93%; 95% CI, 74 to 98) and three additional patients progressed, with a 3-year progression-free survival of 76% (95% CI, 57 to 87). CONCLUSION HCV eradication by DAAs was achieved in 100% of HCV-positive patients with indolent lymphomas not requiring immediate conventional treatment and resulted in non-negligible rate of lymphoma responses. Treatment with DAAs should be considered as the first-line therapy in this setting.
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Affiliation(s)
- Michele Merli
- Division of Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, University of Insubria, Varese, Italy
| | - Sara Rattotti
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Michele Spina
- Division of Medical Oncology and Immune-related Tumors, Centro di Riferimento Oncologico IRCCS, Aviano, Italy
| | - Francesca Re
- Division of Hematology and BMT Center, Azienda Ospedaliera Universitaria, Parma, Italy
| | - Marina Motta
- Division of Hematology, ASST Spedali Civili, Brescia, Italy
| | - Francesco Piazza
- Hematology and Clinical Immunology Unit, Department of Medicine—DIMED, University of Padova, Padova, Italy
| | - Lorella Orsucci
- Division of Hematology, Città della Salute e della Scienza di Torino, Torino, Italy
| | | | - Omar Perbellini
- Division of Hematology, San Bortolo Hospital, Vicenza, Italy
| | - Anna Dodero
- Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Daniele Vallisa
- Division of Hematology, Ospedale Guglielmo da Saliceto, Piacenza, Italy
| | - Alessandro Pulsoni
- Department of Translational and Precision Medicine, Sapienza University of Roma, Roma, Italy
| | - Armando Santoro
- Department of Biomedical Sciences, Humanitas University, IRCCS Humanitas Research Hospital-Humanitas Cancer Center, Milano, Italy
| | - Paolo Sacchi
- Division of Infectious and Tropical Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Valentina Zuccaro
- Division of Infectious and Tropical Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Emanuela Chimienti
- Division of Medical Oncology and Immune-related Tumors, Centro di Riferimento Oncologico IRCCS, Aviano, Italy
| | - Filomena Russo
- Division of Hematology and BMT Center, Azienda Ospedaliera Universitaria, Parma, Italy
| | - Carlo Visco
- Department of Medicine, Section of Hematology, University of Verona, Verona, Italy
| | - Anna Linda Zignego
- Department of Clinical and Experimental Medicine, Interdepartmental Hepatology Center MASVE, University of Firenze, Firenze, Italy
| | | | - Francesco Passamonti
- Division of Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi, University of Insubria, Varese, Italy,Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Stefano Luminari
- Surgical, Medical and Dental Department of Morphological Sciences related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy,Division of Hematology, Azienda Unità Sanitaria Locale-IRCCS, Reggio Emilia, Italy
| | - Marco Paulli
- Unit of Anatomic Pathology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy,Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Raffaele Bruno
- Division of Infectious and Tropical Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy,Department of Clinical, Surgical, Diagnostic, and Paediatric Sciences, University of Pavia, Pavia, Italy
| | - Luca Arcaini
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy,Department of Molecular Medicine, University of Pavia, Pavia, Italy,Luca Arcaini, MD, Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Viale Golgi 19, 27100 Pavia, Italy; e-mail:
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Affiliation(s)
- Davide Rossi
- From the International Extranodal Lymphoma Study Group, Bellinzona; the Institute of Oncology Research, Bellinzona; the Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona; and the Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano - all in Switzerland
| | - Francesco Bertoni
- From the International Extranodal Lymphoma Study Group, Bellinzona; the Institute of Oncology Research, Bellinzona; the Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona; and the Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano - all in Switzerland
| | - Emanuele Zucca
- From the International Extranodal Lymphoma Study Group, Bellinzona; the Institute of Oncology Research, Bellinzona; the Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona; and the Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano - all in Switzerland
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Lue JK, Downs-Canner S, Chaudhuri J. The role of B cells in the development, progression, and treatment of lymphomas and solid tumors. Adv Immunol 2022; 154:71-117. [PMID: 36038195 DOI: 10.1016/bs.ai.2022.07.002] [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: 01/27/2023]
Abstract
B cells are integral components of the mammalian immune response as they have the ability to generate antibodies against an almost infinite array of antigens. Over the past several decades, significant scientific progress has been made in understanding that this enormous B cell diversity contributes to pathogen clearance. However, our understanding of the humoral response to solid tumors and to tumor-specific antigens is unclear. In this review, we first discuss how B cells interact with other cells in the tumor microenvironment and influence the development and progression of various solid tumors. The ability of B lymphocytes to generate antibodies against a diverse repertoire of antigens and subsequently tailor the humoral immune response to specific pathogens relies on their ability to undergo genomic alterations during their development and differentiation. We will discuss key transforming events that lead to the development of B cell lymphomas. Overall, this review provides a foundation for innovative therapeutic interventions for both lymphoma and solid tumor malignancies.
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Affiliation(s)
- Jennifer K Lue
- Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
| | - Stephanie Downs-Canner
- Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
| | - Jayanta Chaudhuri
- Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
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Zhang M, Gao F, Peng L, Shen L, Zhao P, Ni B, Hou J, Huang H. Distinct clinical features and prognostic factors of hepatitis C virus-associated non-Hodgkin's lymphoma: a systematic review and meta-analysis. Cancer Cell Int 2021; 21:524. [PMID: 34627251 PMCID: PMC8502277 DOI: 10.1186/s12935-021-02230-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 09/27/2021] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Increasing evidence suggests that hepatitis C virus (HCV) infection is associated with non-Hodgkin's lymphoma (NHL). However, no clear consensus has been reached about the clinical features and effective treatment of HCV-associated NHL patients. We therefore performed a systematic review and meta-analysis to explore the clinical characteristics and effectiveness of antiviral treatment or rituximab administration among NHL patients with HCV infection. METHODS Eight electronic databases, including PubMed, OVID, EMBASE, Cochrane Library, ClinicalTrials, WANFANG, CNKI, and VIP, were searched for eligible studies up to July 31, 2021. The hazard ratio (HR) or odds ratio (OR) corresponding to the 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by Egger's and Begg's tests. Statistical analysis was performed with RevMan 5.4 software and Stata version 15. RESULTS There were 27 shortlisted articles out of a total of 13,368 NHL patients included in the current meta-analysis. Our results demonstrated that NHL patients with HCV infection had a significantly shorter overall survival (OS: HR 1.89; 95% CI 1.42-2.51, P < 0.0001) and progression-free survival (PFS: HR 1.58; 95% CI 1.26-1.98, P < 0.0001), a lower overall response rate (ORR: OR 0.58, 95% CI 0.46-0.73, P < 0.00001) and a higher incidence of hepatic dysfunction during chemotherapy (OR 5.96; 95% CI 2.61-13.62, P < 0.0001) than NHL patients without HCV infection. HCV-positive NHL patients exhibited an advanced disease stage, an elevated level of LDH, a high-intermediate and high IPI/FLIPI risk as well as a higher incidence of spleen and liver involvement. Moreover, antiviral treatment prolonged survival (OS: HR 0.38; 95% CI 0.24-0.60, P < 0.0001), reduced disease progression [PFS/DFS (disease-free survival): HR 0.63; 95% CI 0.46-0.86, P = 0.003] and reinforced the treatment response (ORR: OR 2.62; 95% CI 1.34-5.11, P = 0.005) among the HCV-infected NHL patients. Finally, rituximab administration was associated with a favourable OS, while liver cirrhosis and low levels of albumin predicted a poor OS for HCV-positive NHL patients. CONCLUSIONS The current study provided compelling evidence about an inferior prognosis and distinct clinical characteristics among HCV-associated NHL patients. Antiviral treatment and rituximab-containing regimens were shown to be efficacious in improving the clinical outcomes of NHL patients with HCV infection.
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Affiliation(s)
- Minyue Zhang
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.,Division of Chinese Medicine, M.D. Prefectural People's Hospital, Chuxiong Yi Autonomous Prefecture, 675500, China
| | - Fei Gao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, 611730, China
| | - Ling Peng
- Division of Chinese Medicine, M.D. Prefectural People's Hospital, Chuxiong Yi Autonomous Prefecture, 675500, China
| | - Lijing Shen
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Peng Zhao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Pharmacy School, Chengdu University of Traditional Chinese Medicine, Chengdu, 611730, China
| | - Beiwen Ni
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
| | - Jian Hou
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
| | - Honghui Huang
- Division of Hematology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
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Ocular adnexal lymphoma: long-term outcome, patterns of failure and prognostic factors in 174 patients. J Hematop 2020. [DOI: 10.1007/s12308-020-00424-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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Orbital and ocular adnexal lymphoma: a review of epidemiology and prognostic factors in Taiwan. Eye (Lond) 2020; 35:1946-1953. [PMID: 32994547 DOI: 10.1038/s41433-020-01198-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 08/19/2020] [Accepted: 09/18/2020] [Indexed: 12/18/2022] Open
Abstract
PURPOSE To investigate the clinical features, prognostic outcomes of patients with orbital and ocular adnexal lymphoma (OALs) in Taiwanese cohort. METHODS Total 112 patients with OALs were retrospectively reviewed. Demographic information such as age, gender, lymphoma subtype, tumor location and treatment modalities were recorded. The primary endpoints were disease-specific survival (DSS), and progression-free survival (PFS). RESULTS The mean patient age was 59.0 ± 15.5 years (range, 23-92 years). The major histopathologic subtypes were mucosa-associated lymphoid tissue (MALT) lymphoma in 76 patients (67.9%), followed by diffuse large B-cell lymphoma (DLBCL) (9.8%), follicular cell lymphoma (FL) (8.0%), and small lymphocytic lymphoma (SLL) (5.4%). The anatomical locations for OALs were the orbit (44 patients, 39.3%), the conjunctiva (31 patients, 27.7%), the lacrimal gland (28 patients, 25.0%), and the eyelid (8 patients, 7.1%). With a mean follow-up time of 74.5 ± 59.8 months (range 6-342 months), the DSS for all patients were 93.1%, 87.7%, and 68.8% at 60, 120, and 180 months' follow-up, respectively. The PFS at 60, 120, and 180 months' follow-up were 86.2%, 61.2%, and 44.6%, respectively. Regarding the analysis of prognostic factors, patients with high grade lymphoma subtype and advanced stage exhibited a worse prognosis. CONCLUSIONS MALT type lymphoma constitutes most of OALs in Taiwan and occurs more frequently than in Western countries. Patients with MALT lymphoma, FL, SLL and earlier stage have favorable outcomes compared with patients of high grade lymphoma and Ann Arbor stage IV lymphoma.
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Gibson SE, Swerdlow SH. How I Diagnose Primary Cutaneous Marginal Zone Lymphoma. Am J Clin Pathol 2020; 154:428-449. [PMID: 32808967 DOI: 10.1093/ajcp/aqaa116] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVES Primary cutaneous marginal zone lymphoma (PCMZL) is 1 of the 3 major subtypes of primary cutaneous B-cell lymphoma. The diagnosis of PCMZL may be challenging, as the differential diagnosis includes benign cutaneous lymphoproliferations as well as other primary or secondary cutaneous B-cell or T-cell lymphomas. This review describes our approach to the diagnosis of PCMZL. METHODS Two cases are presented that illustrate how we diagnose each of the 2 subtypes of PCMZL. The clinicopathologic features of PCMZL and the ways in which these cases can be distinguished from both benign and other neoplastic entities are emphasized. RESULTS A definitive diagnosis of PCMZL requires the incorporation of histologic and immunophenotypic features, molecular genetic studies in some cases, and just as importantly, clinical findings. Emerging data suggest that the heavy chain class-switched cases may be more like a clonal chronic lymphoproliferative disorder. CONCLUSIONS The 2 subtypes of PCMZL create different diagnostic challenges and require the use of a multiparameter approach. Although very indolent, it is important to distinguish PCMZLs from reactive proliferations, because they frequently recur and may require antineoplastic therapies. It is also critical to distinguish PCMZLs from other B- or T-cell lymphomas so that patients are properly evaluated and not overtreated.
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Liţescu M, Baboi ID, Paverman L, Vrabie CD, Iordache N, Coman IS, Lupaşcu-Ursulescu CV, Dina I, Grigorean VT. Incidental case of primary renal lymphoma (PRL) in a patient with chronic hepatitis C infection. Report of a rare case. ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY = REVUE ROUMAINE DE MORPHOLOGIE ET EMBRYOLOGIE 2020; 61:929-934. [PMID: 33817736 PMCID: PMC8112798 DOI: 10.47162/rjme.61.3.33] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 03/19/2021] [Indexed: 12/09/2022]
Abstract
Chronic viral hepatitis C (CHC) is a global health problem, being responsible for about 399 000 deaths worldwide, mostly from cirrhosis and hepatocellular carcinoma. Virus C infection has well known hepatic manifestations - cirrhosis and liver cancer - but the extrahepatic ones are responsible for up to 75% of morbidity in these patients. The well-known hepatitis C virus (HCV) lymphotropism is probably linked with the most frequent extrahepatic manifestations, mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma (BCNHL). We report a very rare entity, the case of an 82-year-old female with Child-Pugh class A viral C cirrhosis associated with a primary renal lymphoma (PRL). PRL is a non-Hodgkin's lymphoma (NHL) localized in the kidney, without any involvement of extrarenal lymphatic tissue. In addition to the case report, some relevant data from the literature were reviewed here.
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Affiliation(s)
- Mircea Liţescu
- Department of General Surgery, Sf. Ioan Emergency Clinical Hospital, Bucharest, Romania
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Ion Daniel Baboi
- Department of Internal Medicine, Sf. Ioan Emergency Clinical Hospital, Bucharest, Romania
| | - Laura Paverman
- Department of Internal Medicine, Sf. Ioan Emergency Clinical Hospital, Bucharest, Romania
| | - Camelia Doina Vrabie
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Pathology, Sf. Ioan Emergency Clinical Hospital, Bucharest, Romania
| | - Niculae Iordache
- Department of General Surgery, Sf. Ioan Emergency Clinical Hospital, Bucharest, Romania
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Ionuţ Simion Coman
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of General Surgery, Bagdasar–Arseni Emergency Clinical Hospital, Bucharest, Romania
| | | | - Ion Dina
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Internal Medicine, Sf. Ioan Emergency Clinical Hospital, Bucharest, Romania
| | - Valentin Titus Grigorean
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of General Surgery, Bagdasar–Arseni Emergency Clinical Hospital, Bucharest, Romania
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13
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Interferon-free compared to interferon-based antiviral regimens as first-line therapy for B-cell lymphoproliferative disorders associated with hepatitis C virus infection. Leukemia 2019; 34:1462-1466. [PMID: 31836855 DOI: 10.1038/s41375-019-0687-2] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 11/16/2019] [Accepted: 12/05/2019] [Indexed: 02/06/2023]
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14
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Sindel A, Al-Juhaishi T, Yazbeck V. Marginal Zone Lymphoma: State-of-the-Art Treatment. Curr Treat Options Oncol 2019; 20:90. [PMID: 31807935 DOI: 10.1007/s11864-019-0687-5] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OPINION STATEMENT Despite being the second most common indolent non-Hodgkin's lymphoma (iNHL), marginal zone lymphoma (MZL) remains largely understudied, and given its underlying disease heterogeneity, it is challenging to define a single treatment approach for these patients. For localized disease, local therapy is recommended such as triple therapy for H. pylori in gastric extranodal MZL, splenectomy for splenic MZL, and radiotherapy for nodal MZL. For disseminated disease with low tumor burden, a watch and wait or single-agent rituximab can be used. However, for symptomatic disease, a similar approach to follicular lymphoma (FL) can be used with chemoimmunotherapy approaches such as bendamustine and rituximab. High FDG uptake is not common in MZL and is not diagnostic by itself of transformation to high-grade lymphoma but informs the choice of the site to be biopsied. Transformation into a large B cell lymphoma is treated with R-CHOP-like regimens. Patients with relapsing disease after at least one CD20-based therapy have several recently approved chemotherapy-free options including B cell receptor inhibitors such ibrutinib (approved specifically in MZL) and immunomodulatory agents such as lenalidomide and rituximab (FDA approved in MZL and FL). Phosphoinositide 3-kinase (PI3K) inhibitors have shown excellent activity in iNHL, specifically in MZL, with breakthrough designation status for copanlisib and umbralisib, allowing off label use of this class of agents in clinical practice. With the availability of prospective clinical trials using chemo-free approaches, specifically those targeting abnormal signaling pathways activated in MZL tumors and its microenvironment, treating physicians are encouraged to enroll patients on these clinical trials in order to better understand the underlying biology, mechanisms of response, and resistance to current therapies and help design future rationale combination strategies.
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Affiliation(s)
- Ariel Sindel
- Department of Internal Medicine, Virginia Commonwealth University, 401 College Street, Box 980035, Richmond, VA, 23298, USA
| | - Taha Al-Juhaishi
- Department of Internal Medicine, Virginia Commonwealth University, 401 College Street, Box 980035, Richmond, VA, 23298, USA
| | - Victor Yazbeck
- Department of Internal Medicine, Virginia Commonwealth University, 401 College Street, Box 980035, Richmond, VA, 23298, USA. .,Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
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15
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Juárez-Salcedo LM, Castillo JJ. Lymphoplasmacytic Lymphoma and Marginal Zone Lymphoma. Hematol Oncol Clin North Am 2019; 33:639-656. [DOI: 10.1016/j.hoc.2019.03.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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16
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Retamozo S, Brito-Zerón P, Ramos-Casals M. Prognostic markers of lymphoma development in primary Sjögren syndrome. Lupus 2019; 28:923-936. [PMID: 31215845 DOI: 10.1177/0961203319857132] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Sjögren syndrome is a systemic autoimmune disease that principally affects women between the fourth and sixth decades of life who present with sicca symptomatology caused by dryness of the main mucosal surfaces. The clinical spectrum of Sjögren syndrome extends from dryness to systemic involvement. Since 1978, Sjögren syndrome has been closely associated with an enhanced risk of lymphoma, one of the most severe complications a patient may develop. Primary Sjögren syndrome patients have a 10-44-fold greater risk of lymphoma than healthy individuals, higher than that reported for systemic lupus erythematosus and rheumatoid arthritis. The close link between lymphoma and Sjögren syndrome is clearly exemplified by the very specific type of lymphoma arising in Sjögren syndrome patients, mainly low-grade B-cell lymphomas (predominantly a marginal zone histological type) with primary extranodal involvement of the major salivary glands (overwhelmingly parotid), with a primordial role of cryoglobulinemic-related markers (both clinical and immunological). The most recent studies support a higher number of risk factors detected in an individual leads to a higher lymphoma risk. A close follow-up of high-risk groups with longitudinal assessments of all known risk factors, including cryoglobulin-related markers and EULAR Sjögren's syndrome disease activity index measurement in particular, is mandatory.
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Affiliation(s)
- S Retamozo
- 1 Instituto de Investigaciones en Ciencias de la Salud (INICSA), Universidad Nacional de Córdoba (UNC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina.,2 Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba, Argentina.,3 Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Barcelona, Spain
| | - P Brito-Zerón
- 3 Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Barcelona, Spain.,4 Department of Medicine, Hospital CIMA-Sanitas, Barcelona, Spain
| | - M Ramos-Casals
- 3 Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Barcelona, Spain.,5 Department of Autoimmune Diseases, ICMiD, Barcelona, Spain.,6 Department of Medicine, University of Barcelona, Barcelona, Spain
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17
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Diamantopoulos P, Dryllis G, Tsourouflis G, Petevi K, Boutsikas G, Rondogianni P, Boutsis D, Korkolopoulou P, Konstantopoulos K, Angelopoulou MK, Meletis J, Kanellis G, Vassilakopoulos TP. A Unique Case of Primary Extranodal Marginal Zone Lymphoma of the Anal Canal. Acta Haematol 2019; 142:87-91. [PMID: 31207598 DOI: 10.1159/000495601] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Accepted: 10/30/2018] [Indexed: 01/28/2023]
Abstract
Marginal zone lymphomas represent approximately 10-12% of all B-cell lymphomas. Extranodal marginal zone lymphomas (EMZL) or mucosa-associated lymphoid tissue (MALT) lymphomas are the most common subtype. Almost half of all MALT lymphomas arise in the gastrointestinal (GI) tract and, while the stomach is the most common site of GI involvement, the small and large intestines can also be involved. Rare cases of MALT lymphoma involving the rectum have been reported; however, to our knowledge, involvement of the anal canal has never been reported in the literature. Here, we describe a unique case of MALT lymphoma of the anal canal. Infectious agents have been implicated in the pathogenesis of MALT lymphomas, possibly through persistent antigenic stimulation of the area; however, in our case no such infection was documented.
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Affiliation(s)
- Panagiotis Diamantopoulos
- Department of Hematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Dryllis
- Department of Hematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Gerasimos Tsourouflis
- Second Department of Surgery, Propedeutic, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Kyriaki Petevi
- Department of Hematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Boutsikas
- Department of Hematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Phoebe Rondogianni
- Department of Nuclear Medicine and PET/CT, Evangelismos General Hospital, Athens, Greece
| | | | | | - Konstantinos Konstantopoulos
- Department of Hematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria K Angelopoulou
- Department of Hematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - John Meletis
- Department of Hematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - George Kanellis
- Department of Hematopathology, Evangelismos General Hospital, Athens, Greece
| | - Theodoros P Vassilakopoulos
- Department of Hematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece,
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18
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Couronné L, Bachy E, Roulland S, Nadel B, Davi F, Armand M, Canioni D, Michot JM, Visco C, Arcaini L, Besson C, Hermine O. From hepatitis C virus infection to B-cell lymphoma. Ann Oncol 2019; 29:92-100. [PMID: 29045541 DOI: 10.1093/annonc/mdx635] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
In addition to liver disorders, hepatitis C virus (HCV) is also associated with extrahepatic immune manifestations and B-cell non-Hodgkin lymphoma (NHL), especially marginal zone lymphoma, de novo or transformed diffuse large B-cell lymphoma and to a lesser extent, follicular lymphoma. Epidemiological data and clinical observations argue for an association between HCV and lymphoproliferative disorders. The causative role of HCV in NHL has been further supported by the response to antiviral therapy. Pathophysiological processes at stake leading from HCV infection to overt lymphoma still need to be further elucidated. Based on reported biological studies, several mechanisms of transformation seem however to emerge. A strong body of evidence supports the hypothesis of an indirect transformation mechanism by which sustained antigenic stimulation leads from oligoclonal to monoclonal expansion and sometimes to frank lymphoma, mostly of marginal zone subtype. By infecting lymphocytes, HCV could play a direct role in cellular transformation, particularly in de novo large B-cell lymphoma. Finally, HCV is associated with follicular lymphoma in a subset of patients. In this setting, it may be hypothesized that inflammatory cytokines stimulate proliferation and transformation of IgH-BCL2 clones that are increased during chronic HCV infection. Unraveling the pathogenesis of HCV-related B-cell lymphoproliferation is of prime importance to optimize therapeutic strategies, especially with the recent development of new direct-acting antiviral drugs.
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Affiliation(s)
- L Couronné
- Department of Hematology, Assistance Publique-Hôpitaux de Paris (APHP), Necker Hospital, Paris, France.,INSERM UMR 1163, CNRS ERL 8254, Imagine Institute, Paris, France.,Paris Descartes-Sorbonne Paris Cité University, Paris, France
| | - E Bachy
- Cancer Research Center of Lyon, INSERM U1052, CNRS UMR 5286, Lyon, France.,Department of Hematology, Lyon Sud Hospital, Lyon, France
| | - S Roulland
- Center of Immunology of Marseille-Luminy, Aix Marseille University, Marseille, France
| | - B Nadel
- Center of Immunology of Marseille-Luminy, Aix Marseille University, Marseille, France
| | - F Davi
- INSERM U1104, Marseille, France.,CNRS UMR 7280, Marseille, France.,Department of Hematology, Pitié-Salpêtrière Hospital, Pierre et Marie Curie University, Paris, France
| | - M Armand
- INSERM U1104, Marseille, France.,CNRS UMR 7280, Marseille, France.,Department of Hematology, Pitié-Salpêtrière Hospital, Pierre et Marie Curie University, Paris, France
| | - D Canioni
- Department of Pathology, Necker Hospital, AP-HP, Paris Descartes-Sorbonne Paris Cité University, Paris, France
| | - J M Michot
- Department of Hematology and Drug Development, Gustave Roussy Institute, Villejuif; France
| | - C Visco
- Department of Cell Therapy and Hematology, San Bortolo Hospital, Vicenza, Italy
| | - L Arcaini
- Department of Molecular Medicine, University of Pavia, Pavia, Italy.,Departement of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - C Besson
- Department of Hematology and Oncology, Hospital of Versailles, Le Chesnay, France.,University of Versailles Saint Quentin en Yvelines, Paris-Saclay University, Communauté Paris-Saclay, Paris, France.,INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, France
| | - O Hermine
- Department of Hematology, Assistance Publique-Hôpitaux de Paris (APHP), Necker Hospital, Paris, France.,INSERM UMR 1163, CNRS ERL 8254, Imagine Institute, Paris, France.,Paris Descartes-Sorbonne Paris Cité University, Paris, France
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19
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Rattotti S, Ferretti VV, Rusconi C, Rossi A, Fogazzi S, Baldini L, Pioltelli P, Balzarotti M, Farina L, Ferreri AJM, Laszlo D, Speziale V, Varettoni M, Sciarra R, Morello L, Tedeschi A, Frigeni M, Defrancesco I, Zerbi C, Flospergher E, Nizzoli ME, Morra E, Arcaini L. Lymphomas associated with chronic hepatitis C virus infection: A prospective multicenter cohort study from the Rete Ematologica Lombarda (REL) clinical network. Hematol Oncol 2019; 37:160-167. [PMID: 30726562 DOI: 10.1002/hon.2575] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2018] [Revised: 01/21/2019] [Accepted: 01/31/2019] [Indexed: 01/16/2023]
Abstract
Chronic hepatitis C virus (HCV) infection is related with an increased risk of non-Hodgkin lymphomas (NHL). In indolent subtypes, regression of NHL was reported after HCV eradication with antiviral therapy (AT). In 2008 in Lombardy, a region of Northern Italy, the "Rete Ematologica Lombarda" (REL, Hematology Network of Lombardy-Lymphoma Workgroup) started a prospective multicenter observational cohort study on NHL associated with HCV infection, named "Registro Lombardo dei Linfomi HCV-positivi" ("Lombardy Registry of HCV-associated non-Hodgkin lymphomas"). Two hundred fifty patients with a first diagnosis of NHL associated with HCV infection were enrolled; also in our cohort, diffuse large B cell lymphoma (DLBCL) and marginal zone lymphoma (MZL) are the two most frequent HCV-associated lymphomas. Two thirds of patients had HCV-positivity detection before NHL; overall, NHL was diagnosed after a median time of 11 years since HCV survey. Our data on eradication of HCV infection were collected prior the recent introduction of the direct-acting antivirals (DAAs) therapy. Sixteen patients with indolent NHL treated with interferon-based AT as first line anti-lymphoma therapy, because of the absence of criteria for an immediate conventional treatment for lymphoma, had an overall response rate of 90%. After a median follow-up of 7 years, the overall survival (OS) was significantly longer in indolent NHL treated with AT as first line (P = 0.048); this confirms a favorable outcome in this subset. Liver toxicity was an important adverse event after a conventional treatment in 20% of all patients, in particular among DLBCL, in which it is more frequent the coexistence of a more advanced liver disease. Overall, HCV infection should be consider as an important co-pathology in the treatment of lymphomas and an interdisciplinary approach should be always considered, in particular to evaluate the presence of fibrosis or necroinflammatory liver disease.
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Affiliation(s)
- Sara Rattotti
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - Chiara Rusconi
- Division of Hematology, Ospedale Niguarda Ca' Granda, Milan, Italy
| | - Andrea Rossi
- Division of Hematology, Ospedali Riuniti, Bergamo, Italy
| | | | - Luca Baldini
- Division of Hematology, Fondazione IRCCS Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | | | | | - Lucia Farina
- Division of Hematology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Andrés J M Ferreri
- Unit of Lymphoid Malignancies, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Daniele Laszlo
- Division of Hematology, Istituto Europeo di Oncologia, Milan, Italy
| | - Valentina Speziale
- Division of Internal Medicine, Ospedale Civile di Legnano, Legnano, Italy
| | - Marzia Varettoni
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Roberta Sciarra
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Lucia Morello
- Division of Hematology, Humanitas Cancer Center, Milan, Italy
| | | | - Marco Frigeni
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.,Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | | | - Caterina Zerbi
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | | | | | - Enrica Morra
- Division of Hematology, Ospedale Niguarda Ca' Granda, Milan, Italy
| | - Luca Arcaini
- Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.,Department of Molecular Medicine, University of Pavia, Pavia, Italy
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20
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Abstract
Orbital lymphomas constitute 50-60% of ocular adnexal lymphomas. A total of 2211 cases of orbital lymphoma with a known subtype have been reported in the last 24 years (1994-2017). The vast majority of orbital lymphomas are of B-cell origin (97%), of which extranodal marginal zone B-cell lymphoma (EMZL) (59%) is the most common subtype, followed by diffuse large B-cell lymphoma (23%), follicular lymphoma (9%), and mantle cell lymphoma (5%). Orbital lymphoma is primarily a disease of the elderly. Gender distribution varies according to lymphoma subtype. However, extranodal marginal zone B-cell lymphoma (53%) and follicular lymphoma (75%) show a female predominance, whereas diffuse large B-cell lymphoma shows an even gender distribution. Mantle cell lymphoma has a striking male predominance of 80%. The histopathological subtype and the clinical stage of the disease are the best indicators of prognosis and patient outcome. Low-grade lymphomas such as extranodal marginal zone B-cell lymphoma and FL have a good prognosis, whereas high-grade lymphomas (diffuse large B-cell lymphoma and mantle cell lymphoma) are associated with a poor prognosis. When managing solitary low-grade lymphomas, radiotherapy is the treatment of choice. Chemotherapy, with or without radiotherapy, should be chosen for disseminated and high-grade lymphomas.
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Affiliation(s)
- Tine Gadegaard Olsen
- Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Steffen Heegaard
- Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Ophthalmology, Rigshospitalet-Glostrup, University of Copenhagen, Copenhagen, Denmark.
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21
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Abdelwahed Hussein MR. Non-Hodgkin’s lymphoma of the oral cavity and maxillofacial region: a pathologist viewpoint. Expert Rev Hematol 2018; 11:737-748. [DOI: 10.1080/17474086.2018.1506326] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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22
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Denlinger NM, Epperla N, William BM. Management of relapsed/refractory marginal zone lymphoma: focus on ibrutinib. Cancer Manag Res 2018; 10:615-624. [PMID: 29628774 PMCID: PMC5877869 DOI: 10.2147/cmar.s133291] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Marginal zone lymphomas (MZLs) consist of a diverse family of malignancies, which are derived from B-cells. The disease subtypes are recognized extranodal, nodal, and splenic MZLs. The disease characteristics, clinical course, and treatment vary considerably based on the site of involvement. In 2017, the US Food and Drug Administration approved ibrutinib, a first in class Bruton’s tyrosine kinase inhibitor that revolutionized the care of chronic lymphocytic leukemia patients; for, the treatment of relapsed/refractory MZL based on pivotal open-label Phase II trial demonstrated an overall response rate of 48%, with a complete response rate of 3%, median progression-free survival of 14.2 months, and median overall survival not yet reached at a median follow-up of 19.4 months. In this review, we aim to summarize the current conundrums in the management of MZL and the evolving role of ibrutinib in the treatment of MZL.
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Affiliation(s)
- Nathan M Denlinger
- Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center (OSUCCC-James), The Ohio State University, Columbus, OH, USA
| | - Narendranath Epperla
- Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center (OSUCCC-James), The Ohio State University, Columbus, OH, USA
| | - Basem M William
- Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center (OSUCCC-James), The Ohio State University, Columbus, OH, USA
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23
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Defrancesco I, Arcaini L. Overview on the management of non-gastric MALT lymphomas. Best Pract Res Clin Haematol 2017; 31:57-64. [PMID: 29452667 DOI: 10.1016/j.beha.2017.11.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Revised: 11/08/2017] [Accepted: 11/10/2017] [Indexed: 12/15/2022]
Abstract
Extranodal marginal zone B-cell lymphomas (EMZLs) of the mucosa-associated lymphoid tissue (MALT) are indolent lymphomas which can present at any extranodal site. The most frequent localizations (other than stomach) are ocular adnexa, salivary gland, skin, lung and thyroid. Chronic inflammation and antigenic stimulation are a potential risk for the development of MALT lymphomas. While Helicobacter Pylori (HP) is known to be associated with gastric MALT lymphoma and antibiotic therapy is effective in the setting of HP-positive, other microorganisms (such as Chlamydophila Psittaci, Campylobacter Jejiuni, Borrelia Burgdoferi) have been implicated in the pathogenesis of non-gastric MALT lymphomas. However, antibiotic therapy has not been extensively investigated for the non-gastric type, except for ocular adnexal MALT lymphoma, which could benefit from an upfront treatment with doxycycline. Surgery, radiotherapy, Rituximab alone or in combination with chemotherapy and "chemo-free" approaches, including lenalidomide, have shown efficacy in the treatment of non-gastric MALT lymphomas.
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Affiliation(s)
| | - Luca Arcaini
- Department of Molecular Medicine, University of Pavia, Pavia, Italy; Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
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24
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Yi S, Yan Y, Xiong W, Lv R, Yu Z, Liu W, Liu E, Li H, Liu H, Li Z, An G, Xu Y, Ru K, Zou D, Qiu L. Distinct clinical characteristics draw a new prognostic model for splenic marginal zone lymphoma in HBV high prevalent region. Oncotarget 2017; 8:98757-98770. [PMID: 29228725 PMCID: PMC5716765 DOI: 10.18632/oncotarget.21931] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2017] [Accepted: 08/27/2017] [Indexed: 12/14/2022] Open
Abstract
Splenic marginal zone lymphoma (SMZL) is a rare indolent B-cell neoplasm with hepatitis virus supposed to involve in the pathogenesis. The characteristics of SMZL derived from Caucasia population and high hepatitis C virus (HCV) infection region have been widely investigated, but few was reported in the Eastern population with HBV prevalent region. We analyzed the clinical characteristics, cytogenetic aberrations and prognostic factors in 160 SMZL patients from China. 25 patients (16%) were HBsAg-positive and 54 (34%) patients with resolved HBV infection. IGH gene usage was analyzed in 39 patients. The preferential usages of IGHV genes were IGHV1-2 (26%), followed by IGHV4-34 (18%) and IGHV2-70 (10%). The patients with HBV infection presented biased IGHV-D-J rearrangements and mutational status. Using three independent factors hemoglobin level, HBsAg positivity and complex karyotype, we developed a new hierarchical prognostic model, which showed a better c-index than the previously reported IIL and HPLL scoring systems in SMZL. In conclusion, SMZL in HBV prevalent region have unique clinical and biological characteristics and new prognostic scoring model should be adopted in this population.
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Affiliation(s)
- Shuhua Yi
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China
| | - Yuting Yan
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China
| | - Wenjie Xiong
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China
| | - Rui Lv
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China
| | - Zhen Yu
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China
| | - Wei Liu
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China
| | - Enbin Liu
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China
| | - Heng Li
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China
| | - Huimin Liu
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China
| | - Zengjun Li
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China
| | - Gang An
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China
| | - Yan Xu
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China
| | - Kun Ru
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China
| | - Dehui Zou
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China
| | - Lugui Qiu
- State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300020, China
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25
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Ayanambakkam A, Ibrahimi S, Bilal K, Cherry MA. Extranodal Marginal Zone Lymphoma of the Central Nervous System. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2017; 18:34-37.e8. [PMID: 29103980 DOI: 10.1016/j.clml.2017.09.012] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Accepted: 09/15/2017] [Indexed: 12/11/2022]
Abstract
Extranodal marginal zone lymphoma of the central nervous system (CNS EMZBL) is a rare disease. We present a review of the literature and describe its presentation, differential diagnosis, treatment options, and outcomes. Systematic search of PubMed, Medline, and Embase databases via the Ovid engine for primary articles and case reports yielded 37 unduplicated peer-reviewed articles of CNS EMZBL. We identified 69 cases in these articles and 1 unreported case at our institution, which were included for this review's analysis. Median age at diagnosis was 55 years (range, 18-78 years), with a female preponderance of 77% (n = 54). Most common presenting symptoms were headache in 43% (n = 30), seizures in 31% (n = 22), and visual defects in 27% (n = 19). The most common treatment modalities were localized therapies, which were provided to 67% (n = 47) of cases. These included radiotherapy in 27% (n = 19), radiotherapy with surgery in 24% (n = 17), and surgery alone in 16% (n = 11). Ninety percent (n = 63) of patients had a median follow-up of 23 months. Complete remission was experienced by 77% (n = 49) patients, and 22% (n = 14) were alive with disease. Three patients had evidence of relapse, and one patient died. CNS EMZBL is an indolent, low-grade, radiosensitive lymphoma with good treatment outcomes and prognosis. It is an important differential to consider in extra-axial dural-based masses. Individualized management plans, with preference given to localized treatment options, should be considered after factoring in the site and extent of disease, its resectability, and the expected adverse effects of systemic therapy.
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Affiliation(s)
- Adanma Ayanambakkam
- Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK
| | - Sami Ibrahimi
- Department of Hematology and Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
| | - Khalid Bilal
- Department of Hematology and Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
| | - Mohamad A Cherry
- Department of Hematology and Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
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26
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Carroll WJ, Peck T, Jenkins TL, Karcioglu ZA. Periocular, periorbital, and orbital pathology in liver disease. Surv Ophthalmol 2017; 62:134-149. [DOI: 10.1016/j.survophthal.2016.11.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Revised: 11/01/2016] [Accepted: 11/04/2016] [Indexed: 12/24/2022]
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27
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Brown NA, Elenitoba-Johnson KSJ. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Hematolymphoid Tumours. Head Neck Pathol 2017; 11:96-109. [PMID: 28247223 PMCID: PMC5340738 DOI: 10.1007/s12105-017-0802-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Accepted: 02/06/2017] [Indexed: 01/13/2023]
Abstract
In 2017, the latest revision to the WHO Classification of Head and Neck Tumours will be released. Similar to the 2005 WHO, the codification of hematopoietic and lymphoid neoplasms of the head and neck is included within chapters pertaining to the nasal cavity and paranasal sinuses, the nasopharynx, the larynx, the oral cavity and oropharynx, the neck and the salivary glands. Herein, we describe both changes to the classification of hematolymphoid neoplasms of the head and neck since the 2005 WHO, as well as recent advances in our understanding of the underlying pathogenesis and molecular pathology of these neoplasms.
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Affiliation(s)
- Noah A Brown
- Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA
| | - Kojo S J Elenitoba-Johnson
- Department of Pathology, Perelman School of Medicine at University of Pennsylvania, 609A Stellar Chance Laboratories, 420 Curie Boulevard, Philadelphia, PA, 1904, USA.
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28
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Hepatitis C virus - Associated marginal zone lymphoma. Best Pract Res Clin Haematol 2017; 30:41-49. [PMID: 28288715 DOI: 10.1016/j.beha.2017.02.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Accepted: 02/06/2017] [Indexed: 12/18/2022]
Abstract
The link between hepatitis C virus (HCV) infection and the development of B-cell non-Hodgkin lymphoma is now well established and based on a number of epidemiological studies. It is further supported by the observation of lymphoma regression after HCV eradication by antiviral treatment. The far most frequent entities are marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL). MZL usually emerge on a background of mixed cryoglobulinemia, a low-grade lymphoproliferation, and often transform into DLBCL, thereby following a multistep oncogenesis process. The role of HCV in lymphomagenesis is not yet fully understood but several mechanisms have been proposed including (i) chronic external stimulation through the B-cell receptor and other surface receptors, and (ii) direct transformation by intracellular viral proteins, the former being probably predominant in MZL. Regression of HCV-associated MZL can be achieved with antiviral therapy and the novel generation of direct-acting antiviral agents appears highly effective and safe for the treatment of these lymphoma.
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29
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Sassone M, Ponzoni M, Ferreri AJM. Ocular adnexal marginal zone lymphoma: Clinical presentation, pathogenesis, diagnosis, prognosis, and treatment. Best Pract Res Clin Haematol 2016; 30:118-130. [PMID: 28288706 DOI: 10.1016/j.beha.2016.11.002] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Accepted: 11/29/2016] [Indexed: 01/08/2023]
Abstract
Ocular adnexal marginal zone lymphoma (OAML) represents 1-2% of all non Hodgkin lymphomas. In the last few years many advances in understanding the pathogenesis and the molecular basis involved in its development have been done. Many potential risk factors have been proposed; a dysregulation of immune response in association with a chronic antigenic stimulation, have been hypothesized as possible pathogenic mechanism. In particular, Chlamydia psittaci infection has been related to OAML arising, and eradicating antibiotic therapy has been addressed as a safe and cost-effective approach. Management of OAML is still heterogeneous and matter of debate. There is no consensus about the best upfront treatment and therapeutic decision should take into account several patient-, lymphoma- and treatment-related factors. Novel agents and chemotherapy-free strategies are being investigated to reduce side effects and improve tumor control. This review is focused in recent knowledge improvements in this lymphoma.
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Affiliation(s)
- Marianna Sassone
- Unit of Lymphoid Malignancies, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milano, Italy
| | - Maurilio Ponzoni
- Unit of Lymphoid Malignancies, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milano, Italy; Pathology Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy; Università Vita e Salute, IRCCS San Raffaele Scientific Institute, Milano, Italy
| | - Andrés J M Ferreri
- Unit of Lymphoid Malignancies, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milano, Italy.
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30
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Fetica B, Pop B, Blaga ML, Fulop A, Dima D, Zdrenghea MT, Vlad CI, Bojan AS, Achimas-Cadariu P, Lisencu CI, Irimie A, Weisenburger DD. High prevalence of viral hepatitis in a series of splenic marginal zone lymphomas from Romania. Blood Cancer J 2016; 6:e498. [PMID: 27834940 PMCID: PMC5148050 DOI: 10.1038/bcj.2016.102] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Affiliation(s)
- B Fetica
- Department of Pathology, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania
| | - B Pop
- Department of Pathology, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania.,Department of Pathology, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - M L Blaga
- Department of Epidemiology and Biostatistics, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania
| | - A Fulop
- Department of Pathology, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania
| | - D Dima
- Department of Hematology, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania
| | - M T Zdrenghea
- Department of Hematology, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania.,Department of Hematology, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - C I Vlad
- Department of Surgery, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania.,Department of Surgery and Gynecologic Oncology, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - A S Bojan
- Department of Hematology, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania.,Department of Hematology, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - P Achimas-Cadariu
- Department of Surgery, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania.,Department of Surgery and Gynecologic Oncology, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - C I Lisencu
- Department of Surgery, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania.,Department of Surgery and Gynecologic Oncology, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - A Irimie
- Department of Surgery, The Oncology Institute 'Prof. dr. I. Chiricuta', Cluj-Napoca, Romania.,Department of Surgery and Gynecologic Oncology, University of Medicine and Pharmacy 'Iuliu Hatieganu', Cluj-Napoca, Romania
| | - D D Weisenburger
- Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA
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31
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Sriskandarajah P, Dearden CE. Epidemiology and environmental aspects of marginal zone lymphomas. Best Pract Res Clin Haematol 2016; 30:84-91. [PMID: 28288721 DOI: 10.1016/j.beha.2016.07.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2016] [Revised: 07/27/2016] [Accepted: 07/27/2016] [Indexed: 02/09/2023]
Abstract
Marginal zone lymphomas (MZLs) account for between 5% and 17% of all non-Hodgkin's lymphomas. MZLs consist of 3 different subtypes with extranodal being the most commonly reported, representing 50-70% of MZL, followed by splenic (20%) and nodal (10%). Median age at presentation varies between these lymphoma sub-types, ranging between 50 and 69 years, with an overall greater incidence noted in males compared to females. Given the rarity of these lymphomas, epidemiologic data has been sparse, although it has been suggested the aetiology is multi-factorial including ethnicity and geographical factors. Other reported associations include autoimmune disease and infection, with Helicobacter pylori and Campylobacter psittaci, being the most commonly reported pathogens. Larger population studies are required to investigate the role of these environmental factors further as these can direct the future management of these lymphomas, through the use of more effective targeted treatments.
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Affiliation(s)
- Priya Sriskandarajah
- Department of Haemato-Oncology, Royal Marsden Hospital NHS Foundation Trust, Downs Road, Sutton, UK; Division of Molecular Pathology, Institute of Cancer Research, 15 Cotswold Road, Sutton, UK.
| | - Claire E Dearden
- Department of Haemato-Oncology, Royal Marsden Hospital NHS Foundation Trust, Downs Road, Sutton, UK.
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32
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Matutes E, Montalban C. Clinical features and management of non-gastrointestinal non-ocular extranodal mucosa associated lymphoid tissue (ENMALT) marginal zone lymphomas. Best Pract Res Clin Haematol 2016; 30:99-108. [PMID: 28288723 DOI: 10.1016/j.beha.2016.07.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Accepted: 07/09/2016] [Indexed: 02/07/2023]
Abstract
Extranodal mucosa associated lymphoid tissue (ENMALT) marginal zone lymphomas may arise at any site of the body. The most frequent localizations other than gastrointestinal and eye are salivary gland, skin, lung and thyroid. These lymphomas usually arise in a setting of inflammation due to a persistent infection or autoimmune diseases such as Sjogren syndrome in salivary MALT lymphomas and Hashimoto's thryroiditis in thyroid lymphomas. They affect middle-aged patients with a female predominance when lymphoma arises in certain locations. Patients often present with localised stage I or II although disseminated disease may be present at diagnosis or relapse in a third of the cases. Biopsy of the affected site is mandatory to establish the diagnosis and a full work-up staging is recommended. The clinical course is indolent and prognosis is good despite that recurrences following response to therapy are frequent. Surgery, radiotherapy and/or Rituximab based regimens are effective in these lymphomas.
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Affiliation(s)
| | - Carlos Montalban
- Department of Hematology, MD Anderson Cancer Center, Madrid, Spain.
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33
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Mucosa-Associated Lymphoid Tissue Lymphoma of the Sigmoid Colon Discovered on Routine Screening Colonoscopy in Patient with Hepatitis C and Helicobacter pylori Infection. ACG Case Rep J 2016; 3:e90. [PMID: 27807552 PMCID: PMC5062656 DOI: 10.14309/crj.2016.63] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2016] [Accepted: 02/18/2016] [Indexed: 02/07/2023] Open
Abstract
Mucosa-associated lymphoid tissue (MALT) lymphoma is predominantly found in the stomach. Rarely, it is found in the proximal colon and even less so in the sigmoid colon. We present a rare case of primary sigmoid colon MALT lymphoma in a patient with concomitant Helicobacter pylori and hepatitis C infection. We also review current imaging, staging, and therapeutic modalities. To our knowledge, this is the first sigmoid colon MALT lymphoma reported in the United States.
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34
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Merli M, Carli G, Arcaini L, Visco C. Antiviral therapy of hepatitis C as curative treatment of indolent B-cell lymphoma. World J Gastroenterol 2016; 22:8447-8458. [PMID: 27784957 PMCID: PMC5064026 DOI: 10.3748/wjg.v22.i38.8447] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 08/02/2016] [Accepted: 08/23/2016] [Indexed: 02/06/2023] Open
Abstract
The association of hepatitis C virus (HCV) and B-cell non-Hodgkin lymphomas (NHL) has been highlighted by several epidemiological and biological insights; however the most convincing evidence is represented by interventional studies demonstrating the capability of antiviral treatment (AT) with interferon (IFN) with or without ribavirin to induce the regression of indolent lymphomas, especially of marginal-zone origin. In the largest published retrospective study (100 patients) the overall response rate (ORR) after first-line IFN-based AT was 77% (44% complete responses) and responses were sustainable (median duration of response 33 mo). These results were confirmed by a recent meta-analysis on 254 patients, demonstrating an ORR of 73%. Moreover this analysis confirmed the highly significant correlation between the achievement of viral eradication sustained virological response (SVR) and hematological responses. Two large prospective studies demonstrated that AT is associated with improved survival and argue in favor of current guidelines’ recommendation of AT as preferential first-line option in asymptomatic patients with HCV-associated indolent NHL. The recently approved direct-acting antiviral agents (DAAs) revolutionized the treatment of HCV infection, leading to SVR approaching 100% in all genotypes. Very preliminary data of IFN-free DAAs therapy in indolent HCV-positive NHL seem to confirm their activity in inducing lymphoma regression.
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35
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Ferri C, Ramos-Casals M, Zignego AL, Arcaini L, Roccatello D, Antonelli A, Saadoun D, Desbois AC, Sebastiani M, Casato M, Lamprecht P, Mangia A, Tzioufas AG, Younossi ZM, Cacoub P. International diagnostic guidelines for patients with HCV-related extrahepatic manifestations. A multidisciplinary expert statement. Autoimmun Rev 2016; 15:1145-1160. [PMID: 27640316 DOI: 10.1016/j.autrev.2016.09.006] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Accepted: 07/19/2016] [Indexed: 02/08/2023]
Abstract
Hepatitis C virus (HCV) infection is responsible for both hepatic and extra-hepatic disorders (HCV-EHDs); these latter are correlated on one hand clearly with HCV lymphotropism causing immune-system dysregulation as well as with viral oncogenic potential, and on the other hand probably with chronic inflammatory status causing cardio-metabolic complications as well as neurocognitive disturbances. The spectrum of HCV-EHDs ranges from mild or moderate manifestations, such as arthralgia, sicca syndrome, peripheral neuropathy, to severe, life-threatening complications, mainly vasculitis and neoplastic conditions. Given the clinical heterogeneity of HCV-EHDs, HCV-infected individuals are inevitably referred to different specialists according to the presenting/prevalent symptom(s); therefore, the availability of comprehensive diagnostic guidelines is necessary for a patient's whole assessment that is decisive for early diagnosis and correct therapeutic approach of various hepatic and HCV-EHDs, regardless of the specific competencies of different physicians or referral centers. In this respect, a multidisciplinary network of experts, the International Study Group of Extrahepatic Manifestations Related to Hepatitis C Virus Infection (ISG-EHCV), was organized with the intention to formulate diagnostic guidelines for the work-up of possible HCV-EHDs. There was a broad consensus among ISG-EHCV members on the proposed guidelines, which essentially are based on two main levels of patient's assessment. At the referral stage, it is proposed that all patients with HCV infection should be invariably examined by means of first-line diagnostic procedures including virological and hepatic parameter evaluation, as well as the detection of clinical findings that may suggest one or more HCV-EHDs. This preliminary assessment should reveal specific HCV-EHDs, which will be deeper analyzed by means of second-line, targeted investigations. The proposed multidisciplinary expert statement represents the first attempt to draw comprehensive diagnostic guidelines for HCV-infected individuals encompassing the entire spectrum of HCV-related disorders, namely typical hepatic manifestations along with less common, often unpredictable HCV-EHDs. The HCV-EHDs may compromise to a substantial degree the overall disease outcome in a significant number of HCV-infected individuals that renders their timely identification and treatment an imperative. In conclusion, the application of standardized but thorough diagnostic guidelines of HCV-EHDs is advisable at the referral stage as well as during the follow-up period of HCV infected patients. It is envisioned that the proposed strategy will result in improvement of clinical outcomes in such patients.
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Affiliation(s)
- Clodoveo Ferri
- Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, 41124 Modena, Italy.
| | - Manuel Ramos-Casals
- Department of Autoimmune Diseases, ICMiD Josep Font Autoimmune Lab, CELLEX-IDIBAPS, Hospital Clinic, Barcelona, Spain
| | - Anna Linda Zignego
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Luca Arcaini
- Department of Molecular Medicine, University of Pavia, Italy; Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Dario Roccatello
- Center of Research of Immunopathology and Rare Diseases, and Nephrology and Dialysis Unit, San G. Bosco Hospital and University of Turin, Italy
| | - Alessandro Antonelli
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, Pisa 56126, Italy
| | - David Saadoun
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Anne Claire Desbois
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Marco Sebastiani
- Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, 41124 Modena, Italy
| | - Milvia Casato
- Department of Clinical Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185 Rome, Italy.
| | - Peter Lamprecht
- Department of Rheumatology & Vasculitis Center, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
| | - Alessandra Mangia
- Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
| | - Athanasios G Tzioufas
- Department of Pathophysiology, School of Medicine, University of Athens, 75 M. Asias st, Building 16, Room 32, 11527 Athens, Greece.
| | - Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital; Beatty Liver and Obesity Program, Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - Patrice Cacoub
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
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36
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Laribi K, Tempescul A, Ghnaya H, Denizon N, Besançon A, Anghel A, Farhi J, Truong C, Lemaire P, Poulain S, Bolle D, Ianotto JC, Baugier de Materre A. The bendamustine plus rituximab regimen is active against primary nodal marginal zone B-cell lymphoma. Hematol Oncol 2016; 35:536-541. [PMID: 27443419 DOI: 10.1002/hon.2334] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Revised: 06/21/2016] [Accepted: 06/29/2016] [Indexed: 12/13/2022]
Abstract
Primary nodal marginal zone lymphoma (NMZL) is a rare disease. There is no current consensus on how to treat it. The bendamustine plus rituximab (BR) regimen is effective for the treatment of follicular and other indolent lymphomas, but its efficacy in NMZL is not known. We analyzed the outcome of 14 patients diagnosed with NMZL (median age 67 years) who were treated with 375 mg/m2 of rituximab on day 1 and 90 mg/m2 of bendamustine on days 1 and 2. The overall and complete response rates were 93% and 71%, respectively. Major toxicity (grade 3/4 neutropenia) occurred in 5% of treatment courses. After a median follow-up of 22 months (range: 18-55), the overall survival and the free survival rates were 100% and 93%, respectively. None of the patients showing a complete or partial response developed secondary myelodysplastic syndrome/acute myeloid leukemia. Bendamustine plus rituximab was found to be an active and well-tolerated regimen leading to the rapid control of disease.
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Affiliation(s)
- Kamel Laribi
- Department of Hematology, Centre Hospitalier du Mans, Le Mans, France
| | - Adrien Tempescul
- Department of Hematology, Institut de Cancéro-Hématologie, CHRU Brest, Brest, France
| | - Habib Ghnaya
- Department of Hematology, Centre Hospitalier du Mans, Le Mans, France
| | - Nathalie Denizon
- Department of Hematology, Centre Hospitalier du Mans, Le Mans, France
| | - Anne Besançon
- Department of Hematology, Centre Hospitalier du Mans, Le Mans, France
| | - Andreea Anghel
- Department of Hematology, Centre Hospitalier du Mans, Le Mans, France
| | - Jonathan Farhi
- Department of Hematology, Centre Hospitalier du Mans, Le Mans, France
| | - Catherine Truong
- Clinical Research Center, Centre Hospitalier du Mans, Le Mans, France
| | - Pierre Lemaire
- Laboratory of Biology and Hematology, Centre Hospitalier du Mans, Le Mans, France
| | - Stephanie Poulain
- Service d'Hématologie-Immunologie-Cytogénétique, Centre Hospitalier de Valenciennes, Valenciennes, France.,Laboratoire d'Hématologie, Centre de Biologie et Pathologie, CHRU de Lille, Lille, France.,INSERM UMR 1172, IRCL, Lille, France
| | - Delphine Bolle
- Department of Pharmacy, Centre Hospitalier du Mans, Le Mans, France
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37
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Autoimmune/Inflammatory Arthritis Associated Lymphomas: Who Is at Risk? BIOMED RESEARCH INTERNATIONAL 2016; 2016:8631061. [PMID: 27429984 PMCID: PMC4939344 DOI: 10.1155/2016/8631061] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Revised: 05/17/2016] [Accepted: 05/25/2016] [Indexed: 12/13/2022]
Abstract
Specific autoimmune and inflammatory rheumatic diseases have been associated with an increased risk of malignant lymphomas. Conditions such as rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE), dermatomyositis, and celiac disease have been consistently linked to malignant lymphomas. Isolated cases of lymphomas associated with spondyloarthropathies and autoinflammatory diseases have also been reported. Direct association between autoimmunity and lymphomagenesis has been reinforced by large epidemiological studies. It is still uncertain whether disease specific determinants or phenotypic or treatment related characteristics increase likelihood of lymphomagenesis in these patients. For example, recent literature has indicated a positive correlation between severity of inflammation and risk of lymphomas among RA and Sjögren's syndrome patients. It is also debated whether specific lymphoma variants are more commonly seen in accordance with certain chronic autoimmune arthritis. Previous studies have revealed a higher incidence of diffuse large B-cell lymphomas in RA and SLE patients, whereas pSS has been linked with increased risk of mucosa-associated lymphoid tissue lymphoma. This review summarizes recent literature evaluating risk of lymphomas in arthritis patients and disease specific risk determinants. We also elaborate on the association of autoimmune arthritis with specific lymphoma variants along with genetic, environmental, and therapeutic risk factors.
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The spectrum of MALT lymphoma at different sites: biological and therapeutic relevance. Blood 2016; 127:2082-92. [DOI: 10.1182/blood-2015-12-624304] [Citation(s) in RCA: 165] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Accepted: 02/01/2016] [Indexed: 12/14/2022] Open
Abstract
Abstract
Extranodal marginal zone (MZ) B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) arise from lymphoid populations that are induced by chronic inflammation in extranodal sites. The best evidence of an etiopathogenetic link is provided by the association between Helicobacter pylori–positive gastritis and gastric MALT lymphoma. Indeed, successful eradication of this microorganism with antibiotics can be followed by gastric MALT lymphoma regression in most cases. Other microbial agents have been implicated in the pathogenesis of MZ lymphoma arising at different sites. Apart from gastric MALT lymphoma, antibiotic therapies have been adequately tested only in ocular adnexal MALT lymphomas where upfront doxycycline may be a reasonable and effective initial treatment of patients with Chlamydophila psittaci–positive lymphoma before considering more aggressive strategies. In all other instances, antibiotic treatment of nongastric lymphomas remains investigational. Indeed, there is no clear consensus for the treatment of patients with gastric MALT lymphoma requiring further treatment beyond H pylori eradication or with extensive disease. Both radiotherapy and systemic treatments with chemotherapy and anti-CD20 antibodies are efficacious and thus the experience of individual centers and each patient’s preferences in terms of adverse effects are important parameters in the decision process.
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Optimizing therapy for nodal marginal zone lymphoma. Blood 2016; 127:2064-71. [PMID: 26989202 DOI: 10.1182/blood-2015-12-624296] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Accepted: 01/27/2016] [Indexed: 12/20/2022] Open
Abstract
Nodal marginal zone lymphoma (NMZL) is a rare form of indolent small B-cell lymphoma which has only been clearly identified in the last 2 decades and which to date remains incurable. Progress in therapeutic management has been slow, largely due to the very small number of patients treated and the heterogeneity of treatments administered; thus, standard-of-care treatment is currently nonspecific for this lymphoma entity. In this review, treatments routinely used to manage adult NMZL patients are presented, principally based on immunochemotherapy (when treatment is needed). Biological research behind the key axes of agents currently under development is described; development of novel agents is heavily based on data from gene profiling and genome-wide sequencing research, uncovering a number of critical deregulated pathways specific to NMZL tumors. These include B-cell receptor, JAK/STAT, NF-κB, NOTCH, and Toll-like receptor signaling pathways, as well as intracellular processes such as the cell cycle, chromatin remodeling, and transcriptional regulation in terms of epigenetic modifiers, histones, or transcriptional co-repressors, along with immune escape via T-cell-mediated tumor surveillance. These pathways are examined in detail and a projection of how the field may evolve in the near future for an efficient personalized treatment approach for NMZL patients is presented.
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Infectious Aetiology of Marginal Zone Lymphoma and Role of Anti-Infective Therapy. Mediterr J Hematol Infect Dis 2016; 8:e2016006. [PMID: 26740867 PMCID: PMC4696464 DOI: 10.4084/mjhid.2016.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Accepted: 11/16/2015] [Indexed: 02/08/2023] Open
Abstract
Marginal zone lymphomas have been associated with several infectious agents covering both viral and bacterial pathogens and in some cases a clear aetiological role has been established. Pathogenetic mechanisms are currently not completely understood. However, the role of chronic stimulation of the host immune response with persistent lymphocyte activation represents the most convincing explanation for lymphoproliferation. Gastric MALT lymphoma is strictly associated with Helicobacter pylori infection and various eradicating protocols, developed due to increasing antibiotic resistance, represent the first line therapy for gastric MALT. The response rate to eradication is good with 80% of response at 1 year; this finding is also noteworthy because it recapitulates cancer cured only by the antibacterial approach and it satisfies the Koch postulates of causation, establishing a causative relationship between Hp and gastric MALT lymphoma. Patients with chronic HCV infection have 5 times higher risk to develop MZL, in particular, an association with splenic and nodal MZL has been shown in several studies. Moreover, there is evidence of lymphoma regression after antiviral therapy with interferon+ribavirin, thus raising hope that newly available drugs, extremely efficient against HCV replication, could improve outcome also in HCV-driven lymphomas. Another case-study are represented by those rare cases of MZL localized to orbital fat and eye conjunctivas that have been associated with Chlamydophila psittaci infection carried by birds. Efficacy of antibacterial therapy against C. psittaci are conflicting and generally poorer than gastric MALT. Finally, some case reports will cover the relationship between primary cutaneous B-cell Lymphomas and Borrelia Burgdorferi.
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41
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Vannata B, Arcaini L, Zucca E. Hepatitis C virus-associated B-cell non-Hodgkin's lymphomas: what do we know? Ther Adv Hematol 2015; 7:94-107. [PMID: 27054025 DOI: 10.1177/2040620715623924] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Epidemiological studies have shown an increased risk of developing B-cell lymphomas in patients with chronic hepatitis C virus (HCV) infection. There is, however, a great geographic variability and it remains unclear whether additional environmental and genetic factors are involved or whether the international discrepancies represent simply a consequence of the variable prevalence of HCV infection in different countries. Other confounding factors may affect the comparability of the different studies, including the method of HCV assessment, the selection of normal controls, the lymphoma classification used and the year of publication. The most convincing evidence for a causal relationship comes from the observation, mainly limited to some indolent subtypes, of B-cell lymphoma regressions after successful HCV eradication with antiviral treatment. Yet, the molecular mechanism of HCV-induced lymphomagenesis are mainly hypothetical. According to most plausible models, lymphoma growth is a consequence of continuous antigenic stimulation induced by the chronic viral infection. This review will summarize the current knowledge on HCV-associated lymphomas and their management.
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Affiliation(s)
- Barbara Vannata
- Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
| | - Luca Arcaini
- Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo and Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Emanuele Zucca
- Lymphoma Unit, Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona 6500, Switzerland
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42
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Zhang Y, Wei Z, Li J, Liu P. Molecular pathogenesis of lymphomas of mucosa-associated lymphoid tissue--from (auto)antigen driven selection to the activation of NF-κB signaling. SCIENCE CHINA-LIFE SCIENCES 2015; 58:1246-55. [PMID: 26612043 DOI: 10.1007/s11427-015-4977-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2015] [Accepted: 10/16/2015] [Indexed: 12/14/2022]
Abstract
Lymphomas of mucosa-associated lymphoid tissue (MALT) are typically present at sites such as the stomach, lung or urinary tract, where lymphoid tissues scatter in mucosa lamina propria, intra- or sub-epithelial cells. The infection of certain pathogens, such as Helicobacter pylori, Chlamydophila psittaci, Borrelia burgdorferi, hepatitis C virus, or certain autoantigens cause these sites to generate a germinal center called the "acquired lymphoid tissue". The molecular pathogenesis of MALT lymphoma is a multi-step process. Receptor signaling, such as the contact stimulation of B cell receptors and CD4 positive T cells mediated by CD40/CD40-ligand and T helper cell type 2 cytokines like interleukin-4, contributes to tumor cell proliferation. A number of genetic alterations have been identified in MALT lymphoma, and among them are important translocations, such as t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21) and t(3;14)(p13;q32). Fusion proteins generated by these translocations share the same NF-κB signaling pathway, which is activated by the caspase activation and recruitment domain containing molecules of the membrane associated guanylate kinase family, B cell lymphoma-10 and MALT1 (CBM) protein complex. They act downstream of cell surface receptors, such as B cell receptors, T cell receptors, B cell activating factors and Toll-like receptors, and participate in the biological process of MALT lymphoma. The discovery of therapeutic drugs that exclusively inhibit the antigen receptor signaling pathway will be beneficial for the treatment of B cell lymphomas in the future.
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Affiliation(s)
- YiAn Zhang
- Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Zheng Wei
- Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Jing Li
- Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Peng Liu
- Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
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Satoh K, Morita T, Fumimoto S, Tsuji H, Ichihashi Y, Ochi K, Hanaoka N, Okada Y, Katsumata T. Rare Pulmonary Metastasis From Thyroid Mucosa-Associated Lymphoid Tissue Lymphoma. Ann Thorac Surg 2015; 100:700-2. [PMID: 26234841 DOI: 10.1016/j.athoracsur.2014.09.070] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Revised: 07/03/2014] [Accepted: 09/09/2014] [Indexed: 10/23/2022]
Abstract
Primary pulmonary lymphomas constitute up to 1% of all pulmonary malignancies. Patients with mucosa-associated lymphoid tissue (MALT) lymphoma represent approximately 90% of patients with primary pulmonary lymphoma. Most pulmonary MALT lymphomas are primary tumors. Pulmonary metastasis is extremely rare. A 65-year-old woman was diagnosed with a thyroid MALT lymphoma in 2008 and underwent total thyroidectomy, followed by chemotherapy. After 5 years of follow-up, she referred to our hospital with an abnormal shadow on a chest roentgenogram. She underwent video-assisted thoracoscopic surgery and was diagnosed with metastatic thyroid MALT lymphoma. Postoperatively, she was treated with chemotherapy, including rituximab, and is alive without recurrence.
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Affiliation(s)
- Kiyoshi Satoh
- Department of Thoracic Surgery, Osaka Medical College Hospital, Takatsuki, Japan.
| | - Takuya Morita
- Department of Thoracic Surgery, Osaka Medical College Hospital, Takatsuki, Japan
| | - Satoshi Fumimoto
- Department of Thoracic Surgery, Osaka Medical College Hospital, Takatsuki, Japan
| | - Hiroyuki Tsuji
- Department of Respiratory Medicine, Osaka Medical College Hospital, Takatsuki, Japan
| | - Yoshio Ichihashi
- Department of Thoracic Surgery, Osaka Medical College Hospital, Takatsuki, Japan
| | - Kaoru Ochi
- Department of Thoracic Surgery, Osaka Medical College Hospital, Takatsuki, Japan
| | - Nobuharu Hanaoka
- Department of Thoracic Surgery, Osaka Medical College Hospital, Takatsuki, Japan
| | - Yoshikatsu Okada
- Department of Pathology, Osaka Medical College Hospital, Takatsuki, Japan
| | - Takahiro Katsumata
- Department of Thoracic Surgery, Osaka Medical College Hospital, Takatsuki, Japan
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44
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Zucca E, Bertoni F, Vannata B, Cavalli F. Emerging role of infectious etiologies in the pathogenesis of marginal zone B-cell lymphomas. Clin Cancer Res 2015; 20:5207-16. [PMID: 25320370 DOI: 10.1158/1078-0432.ccr-14-0496] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Extranodal marginal zone B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) arise from lymphoid populations that are induced by chronic inflammation in extranodal sites. The most frequently affected organ is the stomach, where MALT lymphoma is incontrovertibly associated with a chronic gastritis induced by a microbial pathogen, Helicobacter pylori. Gastric MALT lymphoma therefore represents a paradigm for evaluating inflammation-associated lymphomagenesis, which may lead to a deeper understanding of a possible etiologic association between other microorganisms and nongastric marginal zone lymphomas. Besides infectious etiology, chronic inflammation caused by autoimmune diseases, such as Sjögren syndrome or Hashimoto thyroiditis, can also carry a significant risk factor for the development of marginal zone lymphoma. In addition to the continuous antigenic drive, additional oncogenic events play a relevant role in lymphoma growth and progression to the point at which the lymphoproliferative process may eventually become independent of antigenic stimulation. Recent studies on MALT lymphomas have in fact demonstrated genetic alterations affecting the NF-κB) pathway, a major signaling pathway involved in many cancers. This review aims to present marginal zone lymphoma as an example of the close pathogenetic link between chronic inflammation and tumor development, with particular attention to the role of infectious agents and the integration of these observations into everyday clinical practice. See all articles in this CCR Focus section, "Paradigm Shifts in Lymphoma."
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Affiliation(s)
- Emanuele Zucca
- Lymphoma Unit, Division of Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
| | - Francesco Bertoni
- Lymphoma Unit, Division of Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. Lymphoma and Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland
| | - Barbara Vannata
- Lymphoma Unit, Division of Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
| | - Franco Cavalli
- Lymphoma Unit, Division of Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
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45
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Tasleem S, Sood GK. Hepatitis C Associated B-cell Non-Hodgkin Lymphoma: Clinical Features and the Role of Antiviral Therapy. J Clin Transl Hepatol 2015; 3:134-9. [PMID: 26357640 PMCID: PMC4548354 DOI: 10.14218/jcth.2015.00011] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2015] [Revised: 05/16/2015] [Accepted: 05/18/2015] [Indexed: 12/13/2022] Open
Abstract
The link between chronic hepatitis C virus (HCV) infection and a subset of B-cell non-Hodgkin lymphomas (B-NHL) is strongly supported by epidemiological studies. Evidence demonstrating complete regression of lymphoma after antiviral treatments suggests possible chronic antigenic stimulation for the origin of B-NHL and provides evidence for a virus-mediated lymphomagenesis. B-NHL is a heterogeneous group of lymphomas with varied clinical presentation and may be indolent or aggressive. The optimal management of HCV related B-NHL is not clear. Antiviral treatment may be sufficient for low-grade lymphomas, but chemotherapy is necessary in patients with high grade lymphomas. Interferon (IFN)-based antiviral treatment regimens for HCV infection are limited by poor tolerance and suboptimal antiviral response. Recently approved novel direct acting antiviral (DAA) drugs are highly effective and safe. This has opened a new era for the treatment of HCV related B-NHL alone or in conjunction with chemotherapy. Treatment of HCV associated B-NHL should be performed in an interdisciplinary approach in close consultation with hematologist and hepatologist. In this review, we summarize data regarding clinical features and epidemiology of B-NHL and discuss novel therapeutic approaches, including DAAs, that may prove to be effective in the treatment of HCV associated lymphomas.
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Affiliation(s)
- Syed Tasleem
- Department of Surgery, St. Luke’s Center for Liver Disease, Baylor College of Medicine, Houston, Texas, USA
| | - Gagan K Sood
- Department of Surgery, St. Luke’s Center for Liver Disease, Baylor College of Medicine, Houston, Texas, USA
- Department of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
- Correspondence to: Gagan K Sood, Department of Surgery, St. Luke’s Center for Liver disease, Baylor College of Medicine, 6620 Main Street, Houston, Texas 77030, USA. Tel: +1-832-355-1400, Fax: +1-713-610-2479, E-mail:
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46
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Cappelletti F, Clementi N, Mancini N, Clementi M, Burioni R. Virus-induced preferential antibody gene-usage and its importance in humoral autoimmunity. Semin Immunol 2015; 27:138-43. [PMID: 25857210 DOI: 10.1016/j.smim.2015.03.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Accepted: 03/13/2015] [Indexed: 12/12/2022]
Abstract
It is known that even the adaptive components of the immune system are based on genetic traits common to all individuals, and that diversity is shaped by the lifelong contacts with different non-self antigens, including those found on infectious pathogens. Besides the individual differences, some of these common traits may be more prone to react against a given antigen, and this may be exploited by the infectious pathogens. Indeed, viral infections can deregulate immune response by subverting antibody (Ab) gene usage, leading to the overexpression of specific Ab subfamilies. This overexpression often results in a protective antiviral response but, in some cases, also correlates with a higher likelihood of developing humoral autoimmune disorders. These aspects of virus-induced autoimmunity have never been thoroughly reviewed, and this is the main purpose of this review. An accurate examination of virus specific Ab subfamilies elicited during infections may help further characterize the complex interplay between viruses and the humoral immune response, and be useful in the design of future monoclonal antibody (mAb)-based anti-infective prophylactic and therapeutic strategies.
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Affiliation(s)
- Francesca Cappelletti
- Laboratory of Microbiology and Virology, Università "Vita-Salute" San Raffaele, Milano, Italy
| | - Nicola Clementi
- Laboratory of Microbiology and Virology, Università "Vita-Salute" San Raffaele, Milano, Italy
| | - Nicasio Mancini
- Laboratory of Microbiology and Virology, Università "Vita-Salute" San Raffaele, Milano, Italy
| | - Massimo Clementi
- Laboratory of Microbiology and Virology, Università "Vita-Salute" San Raffaele, Milano, Italy
| | - Roberto Burioni
- Laboratory of Microbiology and Virology, Università "Vita-Salute" San Raffaele, Milano, Italy.
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47
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Abstract
Marginal zone lymphomas (MZL) represent around 8 % of all non-Hodgkin lymphomas. During the last decades a number of studies have addressed the mechanisms underlying the disease development. Extranodal MZL lymphoma usually arises in mucosal sites where lymphocytes are not normally present from a background of either autoimmune processes, such as Hashimoto thyroiditis or Sjögren syndrome or chronic infectious conditions. In the context of a persistent antigenic stimulation, successive genetic abnormalities can progressively hit a B-cell clone among the reactive B-cells of the chronic inflammatory tissue and give rise to a MALT lymphoma. The best evidence of an etiopathogenetic link is available for the association between Helicobacter pylori-positive gastritis and gastric MALT lymphoma. Indeed, a successful eradication of this micro-organism with antibiotics can be followed by gastric MALT lymphoma regression in more than 2/3 of cases. Other microbial agents have been implicated in the pathogenesis of MZL arising in the skin (Borrelia burgdorferi), in the ocular adnexa (Chlamydophila psittaci), and in the small intestine (Campylobacter jejuni). The prevalence of hepatitis C virus (HCV) has also been reported higher in MZL patients (particularly of the splenic type) than in the control population, suggesting a possible causative role of the virus. In non-gastric MALT lymphoma and in splenic MZL the role of the antimicrobial therapy is, however, less clear. This review summarizes the recent advances in Marginal Zone Lymphomas, addressing the critical points in their diagnosis, staging and clinical management.
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48
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Min C, Higuchi T, Koyamada R, Yamaguchi N, Okada S. Pulmonary Extranodal Marginal Zone Lymphoma with Macroglobulinemia and Mixed Cryoglobulinemia Developed in a Patient with Chronic Hepatitis C. Intern Med 2015; 54:2061-4. [PMID: 26278303 DOI: 10.2169/internalmedicine.54.3968] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
We report a 65-year-old woman with a chronic hepatitis C virus infection who developed pulmonary extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissues complicated with macroglobulinemia and mixed cryoglobulinemia. She was treated with immunochemotherapy which resulted in the reduction of both the tumors and the serum immunoglobulin (Ig) M level. This case exemplifies an extensive stimulation upon immune system with derangement in the production of immunoglobulines associated with EMZL, and suggests that it is necessary to consider the possibility of B-cell lymphoma when IgM paraprotein is detected.
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Affiliation(s)
- Chisun Min
- Internal Medicine, St. Luke's International Hospital, Japan
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49
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Vannata B, Zucca E. Hepatitis C virus-associated B-cell non-Hodgkin lymphomas. HEMATOLOGY. AMERICAN SOCIETY OF HEMATOLOGY. EDUCATION PROGRAM 2014; 2014:590-598. [PMID: 25696916 DOI: 10.1182/asheducation-2014.1.590] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Epidemiological studies have demonstrated an increased risk of developing B-cell lymphomas in patients with chronic hepatitis C virus (HCV) infection. However, the strength of the association shows great geographic discrepancies, with higher relative risk in countries with high HCV prevalence. It remains unclear whether additional environmental and genetic factors are involved or if the international variability is simply a consequence of the variable infection prevalence. Therefore, a causal relationship remains controversial. Other confounding factors may affect the comparability of the different studies, including the method of HCV assessment, the selection of normal controls, the lymphoma classification used, and the year of publication. The most convincing proof is the observation, mainly limited to some indolent subtypes, of B-cell lymphoma regressions after HCV eradication with IFN and ribavirin. However, the molecular mechanisms of the HCV-induced lymphomagenesis are mainly hypothetical. According to the model considered to be most plausible, lymphoma growth is a consequence of the continuous antigenic stimulation of the B-cell immunologic response induced by the chronic viral infection. This review summarizes the current epidemiological and biological evidence of a role of HCV in lymphomagenesis, describing the putative mechanisms for a causative relationship. The clinical characteristics and management difficulties of the HCV-associated lymphomas are also discussed. HCV treatment with IFN cannot be given safely in concomitance with cytotoxic lymphoma treatment because of hematological and liver toxicity. However, novel and better tolerated antiviral regimens are under development and will hopefully make the treatment of both lymphoma and hepatitis easier in the future.
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Affiliation(s)
- Barbara Vannata
- Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
| | - Emanuele Zucca
- Lymphoma Unit, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
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50
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Sulyok M, Makara M, Újhelyi E, Vályi-Nagy I. Non-Hodgkin lymphoma and hepatitis C: where we are and what next? Pathol Oncol Res 2014; 21:1-7. [PMID: 25273531 DOI: 10.1007/s12253-014-9845-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Accepted: 09/19/2014] [Indexed: 12/16/2022]
Abstract
The association between hepatitis C virus and certain B-cell non-Hodgkin lymphomas, such as marginal zone lymphomas, is supported by epidemiological studies. The exact pathogenetic mechanism is still unknown but both chronic antigenic stimulation and viral lymphotropism may contribute to the evolution of the malignant clone. Furthermore, the hematologic response following hepatitis C antiviral treatment suggests that the virus may have an etiologic role. Interferon and ribavirin based treatment proved to be successful in small case series of hepatitis C virus associated splenic lymphoma with villous lymphocytes, therefore, it is suggested that antiviral treatment could be an alternative to chemo-immunotherapy. In the near future new more potent direct acting antivirals will make interferon free treatments possible. It is still an open question whether these new short-course regimens are also effective in the treatment of associated lymphomas and what is the importance of the lymphoid reservoir in eliminating HCV.
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Affiliation(s)
- Mihály Sulyok
- St. István and St László Hospital, Hepatology Center, 1097, Albert Flórián str. 5-7, Budapest, Hungary,
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