Cancers

Research

Jump to: Review

12 pages, 10534 KiB

Open AccessArticle

Is There a Role for [¹⁸F]FDG PET-CT in Staging MALT Lymphoma?

by Dan Cohen, Chava Perry, Shir Hazut-Krauthammer, Mikhail Kesler, Yair Herishanu, Efrat Luttwak, Einat Even-Sapir and Irit Avivi

Cancers 2022, 14(3), 750; https://doi.org/10.3390/cancers14030750 - 31 Jan 2022

Cited by 6 | Viewed by 3066

Abstract

The role of ¹⁸F-fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography—computed tomography (PET-CT) in assessing mucosa-associated lymphoid tissue (MALT) lymphoma is debatable. We retrospectively explored the role of [¹⁸F]FDG PET-CT in staging and predicting progression-free-survival (PFS) of patients with newly-diagnosed MALT [...] Read more.

The role of ¹⁸F-fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography—computed tomography (PET-CT) in assessing mucosa-associated lymphoid tissue (MALT) lymphoma is debatable. We retrospectively explored the role of [¹⁸F]FDG PET-CT in staging and predicting progression-free-survival (PFS) of patients with newly-diagnosed MALT lymphoma. Sixty-six studies were included. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were documented in the “hottest” extranodal and nodal lesions. Extranodal lesions and accompanying nodal disease were detected on PET in 38/66 (57.6%) and 13/66 (19.7%) studies, respectively. Detection rate of extranodal lesions differed significantly between those located in tissues with high/heterogeneous (e.g., stomach) vs low/homogenous (e.g., subcutaneous-tissue, lung) physiologic [¹⁸F]FDG-uptake (40.4% vs. 100%, p < 0.01). Nodal lesions had significantly lower SUVmax, MTV and TLG compared with extrandodal lesions in the same patients. Detection and [¹⁸F]FDG-avidity of extranodal lesions were higher in patients with advanced, bulky disease and concomitant marrow/nodal involvement. Increased SUVmax of extranodal lesions predicted shorter PFS (HR 1.10, 95% CI 1.01–1.19, p = 0.02). Higher SUVmax and TLG showed trends towards shorter PFS in patients with localized disease. In conclusion, detection rate of extranodal MALT lymphoma lesions located in tissues with low/homogeneous physiologic [¹⁸F]FDG-uptake is excellent on [¹⁸F]FDG PET-CT. When detected, SUVmax of extranodal lesions may predict PFS. Full article

(This article belongs to the Special Issue Management of MALT Lymphoma)

► Show Figures

Figure 1

14 pages, 2518 KiB

Open AccessArticle

Genetic Characterization and Clinical Features of Helicobacter pylori Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

by Barbara Kiesewetter, Christiane Copie-Bergman, Michael Levy, Fangtian Wu, Jehan Dupuis, Caroline Barau, Luca Arcaini, Marco Paulli, Marco Lucioni, Arturo Bonometti, Antonio Salar, Concepción Fernández-Rodriguez, Miguel A. Piris, Francesco Cucco, Rachel Dobson, Yan Li, Zi Chen, Cyrielle Robe, Ingrid Simonitsch-Klupp, Andrew Wotherspoon, Markus Raderer and Ming Qing Du Show full author list Hide full author list

Cancers 2021, 13(12), 2993; https://doi.org/10.3390/cancers13122993 - 15 Jun 2021

Cited by 10 | Viewed by 2304

Abstract

Background: In Western countries, the prevalence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma has declined over the last three decades. Contemporaneously, H. pylori negative gastric MALT lymphoma is increasingly encountered, and their genetic basis and clinical features remain elusive. Methods: A total of [...] Read more.

Background: In Western countries, the prevalence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma has declined over the last three decades. Contemporaneously, H. pylori negative gastric MALT lymphoma is increasingly encountered, and their genetic basis and clinical features remain elusive. Methods: A total of 57 cases of H. pylori negative gastric MALT lymphoma were reviewed and investigated for chromosome translocation by fluorescence in-situ hybridization and for somatic mutations by the targeted sequencing of 93 genes. Results: MALT1 translocation, most likely t(11;18)(q21;q21)/BIRC3-MALT1, was detected in 39% (22/57) cases, and IGH translocation was further seen in 12 MALT1-negative cases, together accounting for 60% of the cohort. Targeted sequencing was successful in 35 cases, and showed frequent mutations in NF-κB signaling pathways (TNFAIP3 = 23%, CARD11 = 9%, MAP3K14 = 9%), together affecting 14 cases (40%). The NF-κB pathway mutations were mutually exclusive from MALT1, albeit not IGH translocation, altogether occurring in 86% of cases. There was no significant correlation between the genetic changes and clinicopathological parameters. The patients showed a median of progression-free survival (PFS) of 66.3 months, and a significant superior PFS when treated with systemic versus antibiotic therapy (p = 0.004). Conclusion: H. pylori negative gastric MALT lymphoma is characterized by highly frequent genetic changes in the NF-κB signaling pathways. Full article

(This article belongs to the Special Issue Management of MALT Lymphoma)

► Show Figures

Figure 1

17 pages, 2673 KiB

Open AccessArticle

Treatments and Outcomes in Stage I Extranodal Marginal Zone Lymphoma in the United States

by Juan Pablo Alderuccio, Jorge A. Florindez, Isildinha M. Reis, Wei Zhao and Izidore S. Lossos

Cancers 2021, 13(8), 1803; https://doi.org/10.3390/cancers13081803 - 09 Apr 2021

Cited by 7 | Viewed by 1952

Abstract

A considerable number of patients with extranodal marginal zone lymphoma (EMZL) are diagnosed with stage I disease. Information on treatments and survival by primary location remains limited. We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database to assess treatment, primary [...] Read more.

A considerable number of patients with extranodal marginal zone lymphoma (EMZL) are diagnosed with stage I disease. Information on treatments and survival by primary location remains limited. We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database to assess treatment, primary location, and survival of patients with stage I EMZL. Results show that 7961 patients met inclusion criteria. Observation (no treatment) was the most common approach (31%) followed by radiation therapy (RT, 23%). The median overall survival (OS) was 17.3 years (95%CI 16.3 to 18.3). Shorter survival was observed in patients with stage I EMZL compared to expected survival in a cohort derived from the general U.S. population matched by sex, age, and calendar year at diagnosis. However, similar survival was observed in RT-treated patients. We identified age ≥ 60 years (SHR = 4.00, 95%CI 3.10–5.15; p < 0.001), higher grade transformation (SHR = 4.63, 95%CI 3.29–6.52; p < 0.001), and primary lung EMZL (SHR = 1.44, 95%CI 1.05–1.96; p = 0.022) as factors associated with shorter lymphoma-specific survival (LSS). Conversely, primary skin location (SHR = 0.50, 95%CI 0.33–0.77; p = 0.002) was associated with longer LSS. Our results support the use of RT as the preferred approach in localized EMZL. Full article

(This article belongs to the Special Issue Management of MALT Lymphoma)

► Show Figures

Figure 1

Review

Jump to: Research

20 pages, 2132 KiB

Open AccessReview

Clinical Management of Patients with Gastric MALT Lymphoma: A Gastroenterologist’s Point of View

by Tamara Matysiak-Budnik, Kateryna Priadko, Céline Bossard, Nicolas Chapelle and Agnès Ruskoné-Fourmestraux

Cancers 2023, 15(15), 3811; https://doi.org/10.3390/cancers15153811 - 27 Jul 2023

Cited by 1 | Viewed by 1750

Abstract

Gastric mucosa-associated lymphoid tissue (MALT) lymphomas (GML) are non-Hodgkin lymphomas arising from the marginal zone of the lymphoid tissue of the stomach. They are usually induced by chronic infection with Helicobacter pylori (H. pylori); however, H. pylori-negative GML is of increasing [...] Read more.

Gastric mucosa-associated lymphoid tissue (MALT) lymphomas (GML) are non-Hodgkin lymphomas arising from the marginal zone of the lymphoid tissue of the stomach. They are usually induced by chronic infection with Helicobacter pylori (H. pylori); however, H. pylori-negative GML is of increasing incidence. The diagnosis of GML is based on histological examination of gastric biopsies, but the role of upper endoscopy is crucial since it is the first step in the diagnostic process and, with currently available novel endoscopic techniques, may even allow an in vivo diagnosis of GML per se. The treatment of GML, which is usually localized, always includes the eradication of H. pylori, which should be performed even in H. pylori-negative GML. In the case of GML persistence after eradication of the bacteria, low-dose radiotherapy may be proposed, while systemic treatments (immunochemotherapy) should be reserved for very rare disseminated cases. In GML patients, at diagnosis but even after complete remission, special attention must be paid to an increased risk of gastric adenocarcinoma, especially in the presence of associated gastric precancerous lesions (gastric atrophy and gastric intestinal metaplasia), which requires adequate endoscopic surveillance of these patients. Full article

(This article belongs to the Special Issue Management of MALT Lymphoma)

► Show Figures

Figure 1

18 pages, 1403 KiB

Open AccessReview

Extranodal Marginal Zone Lymphoma: Pathogenesis, Diagnosis and Treatment

by Alice Di Rocco, Luigi Petrucci, Giovanni Manfredi Assanto, Maurizio Martelli and Alessandro Pulsoni

Cancers 2022, 14(7), 1742; https://doi.org/10.3390/cancers14071742 - 29 Mar 2022

Cited by 20 | Viewed by 6301

Abstract

Extranodal Marginal Zone Lymphoma (EMZL lymphoma) is an indolent B-cell lymphoma with a median age at diagnosis of about 60 years. It accounts for 7–8% of all B-cell lymphomas. It can occur in various extranodal sites, including stomach, lung, ocular adnexa, and skin; [...] Read more.

Extranodal Marginal Zone Lymphoma (EMZL lymphoma) is an indolent B-cell lymphoma with a median age at diagnosis of about 60 years. It accounts for 7–8% of all B-cell lymphomas. It can occur in various extranodal sites, including stomach, lung, ocular adnexa, and skin; furthermore, the disseminated disease can be found in 25–50% of cases. Several infectious agents, such as Helicobacter pylori (H. Pylori) in the case of gastric Mucosa Associated Lymphoid Tissue (MALT) Lymphoma, can drive the pathogenesis of this cancer, through the autoantigenic stimulation of T cells, but there may also be other factors participating such autoimmune diseases. Initial staging should include total body computed tomography, bone marrow aspirate, and endoscopic investigation if indicated. Fluorescence in situ hybridization (FISH), should be performed to detect the presence of specific chromosomal translocations involving the MALT1 and BCL10 genes, which leads to the activation of the NF-κB signaling pathway. Depending on the location and dissemination of the disease, different therapeutic choices may include targeted therapy against the etiopathogenetic agent, radiotherapy, immunochemotherapy, and biological drugs. The purpose of this review is to illustrate the complex biology and the diagnosis of this disease and to better define new treatment strategies. Full article

(This article belongs to the Special Issue Management of MALT Lymphoma)

► Show Figures

Figure 1

17 pages, 2416 KiB

Open AccessReview

The Biology of Ocular Adnexal Marginal Zone Lymphomas

by Patricia Johansson, Anja Eckstein and Ralf Küppers

Cancers 2022, 14(5), 1264; https://doi.org/10.3390/cancers14051264 - 28 Feb 2022

Cited by 4 | Viewed by 3233

Abstract

This review focuses on the biology of ocular adnexal marginal zone B-cell lymphomas of the mucosa-associated lymphatic tissue (MALT) (OAMZL) subtype. The ocular adnexa includes all structures and tissues within the orbit except for the eye bulb. In the region of the ocular [...] Read more.

This review focuses on the biology of ocular adnexal marginal zone B-cell lymphomas of the mucosa-associated lymphatic tissue (MALT) (OAMZL) subtype. The ocular adnexa includes all structures and tissues within the orbit except for the eye bulb. In the region of the ocular adnexa, MALT lymphomas represent the most common subtype of lymphoma, accounting for around 8% of all non-Hodgkin lymphomas. These lymphomas are often preceded by inflammatory precursor lesions. Either autoantigens or infectious antigens may lead to disease development by functioning as continuous antigenic triggers. This triggering leads to a constitutive activation of the NF-κB signaling pathway. The role of antigenic stimulation in the pathogenesis of OAMZL is supported by the detection of somatic mutations (partially with further intraclonal diversity) in their rearranged immunoglobulin V genes; hence, their derivation from germinal-center-experienced B cells, by a restricted IGHV gene usage, and the validation of autoreactivity of the antibodies in selected cases. In the established lymphomas, NF-κB activity is further enforced by mutations in various genes regulating NF-κB activity (e.g., TNFAIP3, MYD88), as well as recurrent chromosomal translocations affecting NF-κB pathway components in a subset of cases. Further pathogenetic mechanisms include mutations in genes of the NOTCH pathway, and of epigenetic regulators. While gene expression and sequencing studies are available, the role of differential methylation of lymphoma cells, the role of micro-RNAs, and the contribution of the microenvironment remain largely unexplored. Full article

(This article belongs to the Special Issue Management of MALT Lymphoma)

► Show Figures

Figure 1

20 pages, 941 KiB

Open AccessReview

Current Status of the Spectrum and Therapeutics of Helicobacter pylori-Negative Mucosa-Associated Lymphoid Tissue Lymphoma

by Sung-Hsin Kuo, Kun-Huei Yeh, Chung-Wu Lin, Jyh-Ming Liou, Ming-Shiang Wu, Li-Tzong Chen and Ann-Lii Cheng

Cancers 2022, 14(4), 1005; https://doi.org/10.3390/cancers14041005 - 16 Feb 2022

Cited by 10 | Viewed by 3194

Abstract

Helicobacter pylori (HP)-unrelated mucosa-associated lymphoid tissue (MALT) lymphoma includes the majority of extragastric MALT lymphomas and a small proportion of gastric MALT lymphomas. Although the role of first-line antibiotics in treating HP-negative gastric MALT lymphomas remains controversial, HP eradication therapy (HPE)-like regimens may [...] Read more.

Helicobacter pylori (HP)-unrelated mucosa-associated lymphoid tissue (MALT) lymphoma includes the majority of extragastric MALT lymphomas and a small proportion of gastric MALT lymphomas. Although the role of first-line antibiotics in treating HP-negative gastric MALT lymphomas remains controversial, HP eradication therapy (HPE)-like regimens may result in approximately 20–30% complete remission (CR) for patients with localized HP-negative gastric MALT lymphoma. In these patients, H. heilmannii, H. bizzozeronii, and H. suis were detected in sporadic gastric biopsy specimens. Extragastric MALT lymphoma is conventionally treated with radiotherapy for localized disease and systemic chemotherapy for advanced and metastatic diseases. However, a proportion of extragastric MALT lymphomas, such as ocular adnexal lesions and small intestinal lesions, were reported to be controlled by antibiotics for Chlamydophila psittaci and Campylobacter jejuni, respectively. Some extragastric MALT lymphomas may even respond to first-line HPE. These findings suggest that some antibiotic-responsive tumors may exist in the family of HP-negative MALT lymphomas. Two mechanisms underlying the antibiotic responsiveness of HP-negative MALT lymphoma have been proposed. First, an HPE-like regimen may eradicate the antigens of unknown bacteria. Second, clarithromycin (the main component of HPE) may have direct or indirect antineoplastic effects, thus contributing to the CR of these tumors. For antibiotic-unresponsive HP-negative MALT lymphoma, high-dose macrolides and immunomodulatory drugs, such as thalidomide and lenalidomide, have reported sporadic success. Further investigation of new treatment regimens is warranted. Full article

(This article belongs to the Special Issue Management of MALT Lymphoma)

► Show Figures

Figure 1

16 pages, 2745 KiB

Open AccessReview

Development of Organ-Preserving Radiation Therapy in Gastric Marginal Zone Lymphoma

by Daniel Rolf, Gabriele Reinartz, Stephan Rehn, Christopher Kittel and Hans Theodor Eich

Cancers 2022, 14(4), 873; https://doi.org/10.3390/cancers14040873 - 10 Feb 2022

Cited by 1 | Viewed by 2351

Abstract

Gastric marginal zone lymphoma (gMZL) of mucosa-associated lymphoid tissue (MALT) may persist even after H. pylori eradication, or it can be primarily Helicobacter pylori (H. pylori) independent. For patients without the successful eradication of lymphoma, or with progressive disease, treatment options [...] Read more.

Gastric marginal zone lymphoma (gMZL) of mucosa-associated lymphoid tissue (MALT) may persist even after H. pylori eradication, or it can be primarily Helicobacter pylori (H. pylori) independent. For patients without the successful eradication of lymphoma, or with progressive disease, treatment options have historically included partial or total gastrectomy. Presently, in these instances, curative radiation therapy (RT) is the current standard of care. This review emphasizes the historically changing role of radiation therapy in gMZL, progressing from large-volume RT without surgery, to localized RT, on its own, as a curative organ-preserving treatment. This overview shows the substantial progress in radiation therapy during the recent two to three decades, from high-dose, large-field techniques to low-dose, localized target volumes based on advanced imaging, three-dimensional treatment planning, and advanced treatment delivery techniques. RT has evolved from very large extended field techniques (EF) with prophylactic treatment of the whole abdomen and the supradiaphragmatic lymph nodes, applying doses between 30 and 50 Gy, to involved-field RT (IF), to the current internationally recommended involved site radiation therapy (ISRT) with a radiation dose of 24–30 Gy in gMZL. Stage-adapted RT is a highly effective and safe treatment with excellent overall survival rates and very rare acute or late treatment-related toxicities, as shown not only in retrospective studies, but also in large prospective multicenter studies, such as those conducted by the German Study Group on Gastrointestinal Lymphoma (DSGL). Further de-escalation of the radiation treatments with low-dose 20 Gy, as well as ultra-low-dose 4 Gy radiation therapy, is under investigation within ongoing prospective clinical trials of the International Lymphoma Radiation Oncology Group (ILROG) and of the German Lymphoma Alliance (GLA). Full article

(This article belongs to the Special Issue Management of MALT Lymphoma)

► Show Figures

Figure 1

18 pages, 1778 KiB

Open AccessReview

Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma in the Gastrointestinal Tract in the Modern Era

by Eri Ishikawa, Masanao Nakamura, Akira Satou, Kazuyuki Shimada and Shotaro Nakamura

Cancers 2022, 14(2), 446; https://doi.org/10.3390/cancers14020446 - 17 Jan 2022

Cited by 20 | Viewed by 6688

Abstract

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) typically arises from sites such as the stomach, where there is no organized lymphoid tissue. Close associations between Helicobacter pylori and gastric MALT lymphoma or Campylobacter jejuni and immunoproliferative small intestinal disease (IPSID) [...] Read more.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) typically arises from sites such as the stomach, where there is no organized lymphoid tissue. Close associations between Helicobacter pylori and gastric MALT lymphoma or Campylobacter jejuni and immunoproliferative small intestinal disease (IPSID) have been established. A subset of tumors is associated with chromosomal rearrangement and/or genetic alterations. This disease often presents as localized disease, requiring diverse treatment approaches, from antibiotic therapy to radiotherapy and immunochemotherapy. Eradication therapy for H. pylori effectively cures gastric MALT lymphoma in most patients. However, treatment strategies for H. pylori-negative gastric MALT lymphoma are still challenging. In addition, the effectiveness of antibiotic therapy has been controversial in intestinal MALT lymphoma, except for IPSID. Endoscopic treatment has been noted to usually achieve complete remission in endoscopically resectable colorectal MALT lymphoma with localized disease. MALT lymphoma has been excluded from post-transplant lymphoproliferative disorders with the exception of Epstein–Barr virus (EBV)-positive marginal zone lymphoma (MZL). We also describe the expanding spectrum of EBV-negative MZL and a close association of the disease with the gastrointestinal tract. Full article

(This article belongs to the Special Issue Management of MALT Lymphoma)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Management of MALT Lymphoma

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (9 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI