Helicobacter pylori Infection Promotes Gastric Premalignancies and Malignancies Lesions and Demotes Hyperplastic Polyps: A 5 Year Multicentric Study among Cameroonian Dyspeptic Patients.

BACKGROUND: Helicobacter pylori infection is the most well-known risk factor for gastric mucosa abnormalities. However, some geographic regions with persistent high H. pylori infection rates do not suffer from high gastric mucosa lesions incidence. The aim of the study was to establish the relationship between H. pylori infection and gastric pathological features in Cameroon. METHODS: We performed a retrospective study, collecting data from the University Teaching Hospital and the Cameroon Pasteur institute on 1290 patients (mean age 46.31 ± 16.45 years, sex ratio 1.19:1) for whom histological features of the gastric mucosa and H. pylori infection were investigated from 2014 to 2019. Data were extracted from the medical records; hospital computerized databases; or clinical charts of these patients and reviewed according to gender and age of participants. The study was approved by the Ethical Committee of Medical Sciences. RESULT: Approximately 3% (2.56%) of the sample population were with normal gastric mucosa whereas chronic gastritis, atrophic gastritis, intestinal metaplasia, dysplasia, carcinoma, hyperplastic polyps and MALT lymphoma was found in 75.35, 8.2, 7.7, 2.8, 9.3, 1.55 and 0.8% of cases respectively. Unlike hyperplasia (OR= 0.3838), infected participants were in a high risk to develop gastric lesions with an odds ratio of 1.1775, 1.4866, 1.4415, 1.2088, 0.9408 and 0.9075 for gastritis, atrophic gastric, dysplasia, carcinoma, intestinal metaplasia and MALT lymphoma respectively. CONCLUSION: our finding showed that chronic gastritis, gastric premalignancies and malignancies are positively link to Helicobacter pylori infection and that hyperplastic polyp is inversely associated with H. pylori infection in our milieu.

Navigating Through Surgical Implications of Helicobacter pylori: An Up-to-Date Comprehensive Literature Review.

Helicobacter pylori, a gram-negative bacterium, has been identified as a major contributor to gastrointestinal diseases, ranging from gastritis and peptic ulcers to more severe complications such as gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. While pharmacological eradication therapies have been successful in managing H. pylori-associated diseases, the implications of this bacterium on surgical interventions remain a topic of ongoing research and clinical consideration. This comprehensive review aims to elucidate the intricate surgical implications of H. pylori infection. Recent data on the well-known relationship between and the development of gastroduodenal diseases, including peptic ulcers and gastric cancer, is analyzed. Concurrently, Helicobacter pylori infection may have a role in promoting colonic carcinogenesis and, more interestingly, it has also been linked to biliary tract cancers. The review highlights the evolving landscape of H. pylori management in the context of surgical interventions, accentuating the need for further research to delineate optimal strategies for preoperative screening, eradication therapies, and their impact on surgical outcomes and long-term patient prognosis. Comprehending the surgical ramifications of H. pylori infection remains crucial, emphasizing the significance of interdisciplinary approaches and ongoing research effort aimed at enhancing patient care.

Lymphoepithelial lesions in the salivary glands of primary Sjögren's syndrome patients: the perfect storm?

In patients with primary Sjögren's syndrome (pSS), inflamed salivary gland (SG) tissue may contain lymphoepithelial lesions (LELs). LELs are histopathological phenomena whereby B cells are present in hyperplastic ductal epithelium of the SG. Despite the potential role of LELs in pSS pathogenesis, studies on their formation, detection, and prevalence in benign lesions (not complicated with lymphoma) are scarce. Recent evidence however shows that LELs are present in approximately half of the patients with pSS, both in minor and major SGs. Migration of a small number of B cells into the epithelium appears to be a critical initial step in LEL formation. These intra-epithelial B cells are proliferative, exhibit an innate-like phenotype, and may be linked to MALT lymphoma development. Alongside intra-epithelial B cells, the hyperplastic epithelial partner in LELs also engages in the local immune reaction. Epithelial cells are a source of cytokines and chemokines, with CXCL10 in particular playing a potential role in LEL formation. Importantly, LELs also have a negative impact on the maintenance of SG homeostasis by SG progenitor cell (SGPC) populations, likely due to dysregulation of SGPC lineage commitment or induction of plasticity. In conclusion, LEL formation mirrors a perfect storm of B and epithelial cell interaction culminating in increased risk of B cell derailment and SGPC dysregulation in pSS patients. We therefore argue that attenuation of LEL formation is an important treatment goal to preserve SG function and prevent B cell derailment in pSS.

Bacterial infection-driven lymphomagenesis.

PURPOSE OF REVIEW: The first convincing evidence for a causal relationship between bacterial infection and lymphomagenesis came from the link between gastric lymphoma and chronic Helicobacter pylori gastritis. This review will summarize the current epidemiological, clinical, and biological evidence of a causative role of bacteria in the development of malignant lymphomas, particularly, the extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type. RECENT FINDINGS: Other microorganisms have been associated with specific extranodal lymphoma sites with variable and not always definitive, evidence, including Chlamydia psittaci , Borrelia burgdorferi , Campylobacter jejuni and, most recently, Coxiella Burnetii . According to most plausible models, lymphoma growth is a consequence of continuous antigenic stimulation induced by chronic infection. However, some evidence of a direct oncogenic role of H. pylori has been provided, too. SUMMARY: Lymphomas are not the result of a single cause but multifactorial diseases, influenced by a variety of genetic and environmental elements. Hence, ascertaining the specific contribution of bacterial infections is not always easy. Nevertheless, the eradication of the associated chronic infection may result in sustained lymphoma regression. Moreover, the association between infections and lymphoma may offer opportunities for reducing lymphoma incidence by preventing the predisposing infections or treating them early.

Chemotherapy is an efficient treatment in primary CNS MALT lymphoma.

BACKGROUND: Mucosae-associated lymphoid tissue (MALT) lymphomas are a rare and poorly understood form of primary central nervous system lymphoma (PCNSL). The aim of this study was to better describe these tumors, their management and their long-term prognosis. METHODS: Patients with primary CNS MALT lymphoma (PCNSML) were retrospectively selected from the database on PCNSL of the Pitié-Salpêtrière Hospital. RESULTS: Of 662 PCNSL, 11 (1.7%) PCNSML (9 females and 2 males, median age: 56 years) were selected. The median time from first symptoms to diagnosis was 13 months. Location was dural in 8 cases and parenchymal in 3 cases. The disease was multifocal/diffuse in 7 cases. In first line, all patients received chemotherapy (high-dose methotrexate (HD-MTX) based chemotherapy (n = 4) and non-HD-MTX-based chemotherapy (n = 7)), preceded by surgery in 4 cases. None received radiotherapy. According to the IPCG (International PCNSL Collaborative Group) criteria, the overall response rate was 7/11 (64%). At latest news, 5 patients had persistent contrast enhancement, stable with no treatment since a median of 57 months, raising the question of complete response despite persisting contrast enhancement. No patient developed neurotoxicity except for one patient who subsequently received radiotherapy. The median follow-up was 109 months. The median progression-free survival was 78.0 months and the 10-year overall survival rate was 90%. CONCLUSION: This is the largest series demonstrating that chemotherapy is an efficient treatment in PCNSML, with an excellent long-term outcome and the absence of neurotoxicity, and calling into question the relevance of the IPCG criteria for the evaluation of response.

NOTCH signaling in the pathogenesis of splenic marginal zone lymphoma-opportunities for therapy.

NOTCH signaling is a highly conserved pathway mediated by four receptors (NOTCH 1-4) playing critical functions in proliferation, differentiation, and cell death. Under physiologic circumstances, NOTCH2 is a key regulator in marginal zone differentiation and development. Over the last decade, growing data demonstrated frequent NOTCH2 mutations in splenic marginal zone lymphoma (SMZL) underscoring its critical role in the pathogenesis of this disease. Moreover, NOTCH2 specificity across studies supports the rationale to assess its value as a diagnosis biomarker in a disease without pathognomonic features. These data make NOTCH signaling an appealing target for drug discovery in SMZL; however, prior efforts attempting to manipulate this pathway failed to demonstrate meaningful clinical benefit, or their safety profile prevented further development. In this review, we discuss the current knowledge of NOTCH implications in the pathogenesis and as a potential druggable target in SMZL.

Clinico-biological features and outcome of patients with splenic marginal zone lymphoma with histological transformation.

We describe 36 patients with splenic marginal zone lymphoma (SMZL) with transformation (SMZL-T), including 15 from a series of 84 patients with SMZL diagnosed at the Hospital Clinic of Barcelona (HCB) and 21 diagnosed with SMZL-T in other centres. In the HCB cohort, the cumulative incidence of transformation at 5 years was 15%. Predictors for transformation were cytopenias, hypoalbuminaemia, complex karyotype (CK) and both the Intergruppo Italiano Linfomi (ILL) and simplified Haemoglobin, Platelet count, lactate dehydrogenase (LDH) and extrahilar Lymphadenopathy (HPLL)/ABC scores (P < 0·05). The only independent predictor for transformation in multivariate analysis was CK [hazard ratio (HR) 4·025, P = 0·05]. Patients with SMZL-T had a significantly higher risk of death than the remainder (HR 3·89, P < 0·001). Of the 36 patients with SMZL-T, one developed Hodgkin lymphoma and 35 a diffuse large B-cell lymphoma, 71% with a non-germinal centre phenotype. The main features were B symptoms, lymphadenopathy, and high serum LDH. CK was observed in 12/22 (55%) SMZL-T and fluorescence in situ hybridisation detected abnormalities of MYC proto-oncogene, basic helix-loop-helix transcription factor (MYC), B-cell leukaemia/lymphoma 2 (BCL2) and/or BCL6 in six of 14 (43%). In all, 21 patients received immunochemotherapy, six chemotherapy, one radiotherapy and three splenectomy. The complete response (CR) rate was 61% and the median survival from transformation was 4·92 years. Predictors for a worse survival in multivariate analysis were high-risk International Prognostic Index (HR 5·294, P = 0·016) and lack of CR (HR 2·67, P < 0·001).

Obesity Is a Risk Factor Associated with H. pylori-negative MALT Lymphoma of Stomach.

OBJECTIVE: More than 90% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are attributed to Helicobacter pylori infections. However, the pathogenesis of H. pylori-negative MALT lymphomas is controversial, and additional etiologies need to be investigated. MATERIALS: A retrospective study of gastric MALT lymphoma cases over a 15-year period revealed 56 cases. The H. pylori status, clinical information, and body mass index (BMI) data were collected. The results of the urea breath test, serology, stool antigen, and previous biopsy results were documented. RESULTS: The 56 cases had an average height of 166.57 cm (range, 147.3-190.5), weight of 83.98 kg (range 55-153.1), and body mass index (BMI) of 30.34 kg/m2 (range, 17.96-49.77). Twenty-one cases were H. pylori-positive (37.5%), with a mean BMI of 27.36 kg/m2 (range, 17.96-47.25), and BMI>30 kg/m2 in 5 (23.8%) patients. Thirty-five cases were H. pylori-negative, with a mean BMI of 31.90 kg/m2 (range, 18.17-49.77), and 20 (57.1%) having BMI>30 kg/m2. A Fisher's exact test and two-tailed test showed a statistically significant difference between the two groups. CONCLUSION: Obesity leads to a baseline state of chronic inflammation and increased production of pro-inflammatory cytokines that can stimulate the lymphocytes, leading to lymphomatous proliferation. Our study suggests a potential correlation between obesity and the risk of development of primary gastric MALT lymphoma.

Hepatitis C virus-associated indolent B-cell lymphomas: A review on the role of the new direct antiviral agents therapy.

Several studies have suggested that hepatitis C virus (HCV) may be the causative agent of some B-cell non-Hodgkin lymphomas (B-NHL). Several authors have demonstrated that pegylated interferon (Peg-IFN) plus ribavirin (RBV) can revert indolent low-grade B-NHL by inducing HCV eradication. Presently, the combination therapy (IFN plus RBV) has been abandoned since the direct antiviral agents (DAAs) have shown very high efficacy in achieving sustained virologic response (SVR) (range: 95%-100%). This review analyzed DAAs efficacy in HCV-associated indolent low-grade NHL, providing a detailed literature review. Overall, 122 B-cell NHL patients were treated with DAAs: complete/partial hematological response, particularly in those with marginal zone lymphoma, was obtained in most cases. Hematological response, obtained either with DAAs or IFN-based therapy, was similar. Nonetheless, DAAs therapy showed better tolerability and higher SVR. A fraction of the patients, despite SVR, underwent hematologic relapse or progression. In these cases, a recovery treatment with immunotherapy, or chemoimmunotherapy, had to be planned. In conclusion, data obtained from published studies mostly agree that HCV eradication with DAAs should be considered as the first-line treatment in HCV-related NHL. In fact, the chronic viral stimulation of the immune system might be the primary pathogenic mechanism in disease development and progression.

Helicobacter pylori and Gastric Cancer.

Helicobacter pylori is present in approximately one-half of the world's population. There are significant differences in prevalence based on region, age, race/ethnicity, and socioeconomic status. H pylori is the most common cause of infection-related cancers. Studies have demonstrated the relationship between H pylori infection and gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. H pylori has features and enzymatic properties allowing it to survive in the acidic stomach environment, and has specific virulence factors that promote an increased risk of gastric pathology. Eradication of H pylori is first-line therapy for mucosa-associated lymphoid tissue lymphoma and decreases the risk of gastric adenocarcinoma.

Dissecting the Helicobacter pylori-regulated transcriptome of B cells.

Persistent infections with the bacterial group-I carcinogen Helicobacter pylori (H. pylori) have been associated with a broad range of gastric disorders, including gastritis, ulceration, gastric cancer or mucosa-associated lymphoid tissue (MALT) lymphoma. Pathogenesis of H. pylori requires a balance between immune tolerance and defense. Although H. pylori induces inflammatory responses, the immune system cannot eliminate the pathogen. The detailed molecular mechanisms of how H. pylori interferes with cells of the immune system, in particular infiltrated B cells, are not well investigated. Previously, it was shown that the bacterial effector and oncoprotein cytotoxin-associated gene A (CagA) is delivered into B cells followed by its tyrosine-phosphorylation. To investigate the functional consequences in B cells colonized by CagA-positive H. pylori, we analyzed the global transcriptome of H. pylori-infected Mec-1 cells by RNA sequencing. We found 889 differentially expressed genes (DEGs) and validated JUN, FOSL2, HSPA1B, SRC, CXCR3, TLR-4, TNF-α, CXCL8, CCL2, CCL4, MHC class I and MHC class II molecules by qPCR, western blot, flow cytometry and ELISA assays. The H. pylori-specific mRNA expression signature reveals a downregulation of inflammation- and migration-associated genes, whereas central signal transduction regulators of cell survival and death are upregulated.

Unique expansion of IL-21+ Tfh and Tph cells under control of ICOS identifies Sjögren's syndrome with ectopic germinal centres and MALT lymphoma.

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

APRIL-producing eosinophils are involved in gastric MALT lymphomagenesis induced by Helicobacter sp infection.

The roles of the inflammatory response and production of a proliferation-inducing ligand (APRIL) cytokine in gastric mucosa-associated lymphoid tissue (MALT) lymphomagenesis induced by Helicobacter species infection are not clearly understood. We characterized the gastric mucosal inflammatory response associated with gastric MALT lymphoma (GML) and identified APRIL-producing cells in two model systems: an APRIL transgenic mouse model of GML induced by Helicobacter infection (Tg-hAPRIL) and human gastric biopsy samples from Helicobacter pylori-infected GML patients. In the mouse model, polarization of T helper 1 (tbet), T helper 2 (gata3), and regulatory T cell (foxp3) responses was evaluated by quantitative PCR. In humans, a significant increase in april gene expression was observed in GML compared to gastritis. APRIL-producing cells were eosinophilic polynuclear cells located within lymphoid infiltrates, and tumoral B lymphocytes were targeted by APRIL. Together, the results of this study demonstrate that the Treg-balanced inflammatory environment is important for gastric lymphomagenesis induced by Helicobacter species, and suggest the pro-tumorigenic potential of APRIL-producing eosinophils.

Transcriptome hallmarks in Helicobacter pylori infection influence gastric cancer and MALT lymphoma.

Aim: Altered long noncoding RNA (lncRNA) and mRNA is vital in the progression from Helicobacter pylori (H. pylori, HP) infection to gastric cancer (GC) and mucosa-associated lymphoid tissue (MALT) lymphoma. Materials & methods: Five independent Gene Expression Omnibus datasets (GSE5081, GSE84433, GSE15459, GSE66229 and GSE25638) were included in our study. Results: Differentially expressed lncRNAs and mRNAs in both H. pylori-positive gastritis and GC tissues were identified. Using two GC cohorts, the H. pylori-related mRNA DYNC1I1 and MMP7 were independent predictors of overall survival. Moreover, the expressions of lncRNA GHRLOS and 44 mRNAs were significantly changed in gastric MALT lymphoma patients. Conclusion: The lncRNA/mRNA response to H. pylori infection in gastritis and GC influence the outcome of GC and progression of MALT lymphoma.

Helicobacter pylori: A Review of Current Diagnostic and Management Strategies.

As one of the most prevalent infections globally, Helicobacter pylori (H. pylori) continues to present diagnostic and therapeutic challenges for clinicians worldwide. Diagnostically, the "test-and-treat" strategy is the recommended approach for healthcare practitioners when managing this potentially curable disease. The choice of testing method should be based on several factors including patient age, presenting symptoms, and medication use, as well as test reliability, availability, and cost. With rising antibiotic resistance, particularly of macrolides, care must be taken to ensure that therapy is selected based on regional resistance patterns and prior antibiotic exposure. In the USA, macrolide antibiotic resistance rates in some areas have reached or exceeded a generally accepted threshold, such that clarithromycin triple therapy may no longer be an appropriate first-line empiric treatment. Instead, bismuth quadruple therapy should be considered, while levofloxacin-based or alternative macrolide-containing therapies are also options. Once treated, it is essential to test for eradication as untreated H. pylori is associated with serious complications including peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. This review article aims to consolidate current knowledge of H. pylori infection with a particular emphasis on diagnostic and treatment strategies.

[Clinicopathological analysis of mucosa associated lymphoid tissue lymphoma secondary to Sjögren' s syndrome in salivary gland].

OBJECTIVE: To analyze the clinicopathological characteristics of mucosa associated lymphoid tissue (MALT) lymphoma secondary to Sjögren' s syndrome (SS) (SS-MALT lymphoma) in salivary gland and to explore the value of the combined application of histopathological morphology, protein expression and molecular phenotype in pathological diagnosis and prognostic evaluation of SS-MALT lymphoma. METHODS: Sixteen patients with SS-MALT lymphoma were collected from 260 patients who were diagnosed with SS in Peking University School and Hospital of Stomatology from January 1997 to December 2016. Twelve patients with non-MALT lymphoma secondary to SS (non-SS-MALT lymphoma) in salivary gland were selected as controls. The clinical data of the patients were retrospectively reviewed and analyzed. All the patients were followed up until December 20, 2019. Hematoxylin-eosin staining, immunohistochemistry, polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) techniques were used to observe the histologic characteristics and to detect the manifestations of light chain restrictive expression, immunoglobulin (Ig) gene clonal rearrangement, chromosome translocation and gene abnormality, so as to evaluate their values in pathological diagnosis and prognostic evaluation. RESULTS: The malignant transformation rate of SS to MALT lymphoma was about 6.15%, ranged from 3 to 240 months, during which 2 patients died due to high-level deterioration. Microscopically, the acini of the glandular tissue were atrophied and destroyed. The tumor cells dominated by central cell-like lymphocytes grew diffusely, destroying the epithelial islands. All SS-MALT lymphoma cases were positive in CD20 and Pax5. Half of them had the Ki-67 proliferation index of 10% or less, and half greater than 10%. 93.75% cases expressed AE1/AE3 protein, which showed the residual glandular epithelium. All the tumor cells were negative in CD3ε, and the plasma cells were detected by CD138 antigen. The light chain restrictive expression of κ and λ was 37.5% in SS-MALT lymphoma group. The positive detection rates of immunoglobulin heavy chain (IgH)-FR1, IgH-FR2, IgH-FR3, immunoglobulin kappa chain (IgK)-A, and IgK-B in SS-MALT lymphoma group were 33.3%, 53.3%, 33.3%, 20.0%, and 26.7%, respectively, and 93.3% when together used with IgH and IgK. The positive rates of the MALT1, IGH and BCL6 genes with dual color break-apart probes were 36.4%, 27.3% and 27.3%, and the detection rate of chromosome translocation and gene abnormality by applying the three probes was 72.7%. CONCLUSION: There are no specific histological characteristics and protein phenotypes in the histologic diagnosis of SS-MALT lymphoma in salivary gland. The combined application of histopathological manifestations, immunohistochemistry, PCR and FISH techniques helps the accurate pathologic diagnosis of the disease. Although SS-MALT lymphoma is considered as an indolent lymphoma with a relatively favorable prognosis, the regular return visit and long-term follow-up should be conducted to detect the clues of recurrence and advanced deterioration.

Marginal Zone Lymphoma: State-of-the-Art Treatment.

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.

An unusual presentation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma following blunt abdominal trauma.

A 79-year-old woman presented to the emergency department following a motor vehicle collision. As part of her workup she underwent a CT scan which identified a large mass containing calcifications centred around the gastric antrum, and while being assessed she produced 500 mL of haematemesis. An endoscopy revealed an area of friable mucosa the nature of which was uncertain, and multiple biopsies revealed amyloid deposition and active Helicobacter pylori gastritis. Following review of imaging and pathology, a diagnosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma was established. She was treated with quadruple therapy for the H. pylori and at 6-month follow-up she is asymptomatic with repeat endoscopy revealing healing of the ulceration and no biopsy evidence of H. pylori or MALT.