Treatment Outcomes in Patients with Conjunctival Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma.

Purpose: To report the outcomes of different therapies in patients with conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma. Patients and Methods: This retrospective study included patients diagnosed with conjunctival MALT lymphoma between August 2000 and April 2022. Patients were classified into three groups according to their treatment: an observation group, a radiation therapy (RT) group, and a rituximab group (rituximab with or without chemotherapy). We analyzed overall survival (OS), overall, local, and systemic relapse-free survival (RFS), and adverse events after treatment. Results: This study included 15 patients (22 eyes). The 10-year OS was 100%. The 2-, 5-, and 10-year overall RFS rates were 80.1%, 41.2%, and 41.2% in all patients, respectively. The 2- and 5-year local RFS rates in the observation group were 100% and 0%, respectively. The 2-, 5-, and 10-year local RFS rates were 87%, 87%, and 87% in the RT group and 83%, 67%, and 67% in the rituximab group, respectively. The 2- and 5-year systemic RFS rates in the observation group were both 100%, and the 2-, 5-, and 10-year systemic RFS rates were 92%, 55%, and 55% in the RT group, and 100%, 60%, and 60% in the rituximab group, respectively. After RT, 53.3% of the eyes developed cataracts and 75% of these were treated with cataract surgery. In addition, 53.3% of the eyes developed dry eyes and were treated with eye drops. Rituximab with or without chemotherapy resulted in some systemic adverse events, but these improved following symptomatic therapies. Conclusion: RT resulted in good local control of conjunctival MALT lymphoma; however, systemic relapse may occur during long-term follow-up. Local and/or systemic relapse may also occur during long-term follow-up in patients treated by observation or rituximab with or without chemotherapy. Patients with conjunctival MALT lymphoma should be followed-up carefully for as long as possible after treatment.

Treatment-Resistant Immunoproliferative Small Intestinal Disease (IPSID) Leading to Lymphoma.

Immunoproliferative small intestinal disease (IPSID) is a distinct variant of mucosa-associated lymphoid tissue (MALT) lymphoma, often linked to chronic Campylobacter jejuni infection. Characterized as an extra-nodal marginal zone B-cell lymphoma, IPSID predominantly affects the proximal small intestine. It features lymphoplasmacytic infiltration and deposition of monotypic α-heavy chains in the lamina propria, leading to blunted intestinal villi, malabsorption, and protein-losing enteropathy. IPSID's clinical spectrum ranges from lymphoid infiltration to malignant diffuse large B-cell lymphoma. Similar to MALT lymphoma, early-stage IPSID can be resolved with antibiotic therapy. This case study documents a 50-year-old Nigerian woman presenting with recurrent watery diarrhea, abdominal pain, and weight loss, unresponsive to antibiotics. A 50-year-old female immigrant from Nigeria presented with recurrent watery diarrhea, abdominal pain, and significant weight loss, all refractory to antibiotic treatment. Initial diagnostic investigations revealed a positive Campylobacter stool antigen, mesenteric lymphadenopathy on CT and gallium scans, and diffuse mucosal lymphoplasmacytic infiltration with villi flattening on small bowel biopsies. An octreotide scan identified a reactive mesenteric lymph node, confirmed by surgical biopsy as reactive lymphadenitis. The patient was diagnosed with IPSID and commenced antibiotic therapy, which initially resolved her symptoms. However, she experienced frequent recurrences requiring multiple hospitalizations and repeated courses of intravenous antibiotics. Eventually, the disease progressed to lymphoma, necessitating chemotherapy initiation. This case underscores the diagnostic complexities of IPSID, particularly in distinguishing it from other causes of mesenteric lymphadenopathy. It also highlights the challenges in preventing disease progression from a benign to a malignant state despite appropriate antibiotic treatment. Given IPSID's prevalence in endemic regions, it should be considered in differential diagnoses for similar presentations. Continuous monitoring is crucial to evaluate therapeutic response and mitigate the risk of progression to lymphoma. IPSID presents a significant diagnostic and therapeutic challenge. This case exemplifies the necessity for heightened clinical awareness, especially in patients from endemic regions, and the importance of rigorous monitoring to prevent malignant transformation. Further research is warranted to elucidate the mechanisms behind IPSID progression in certain patients despite repeated antibiotic interventions.

First detection of PCV4 in swine in the United States: codetection with PCV2 and PCV3 and direct detection within tissues.

Since PCV4 was first described in 2019, the virus has been identified in several countries in Southeast Asia and Europe. Most studies have been limited to detecting PCV4 by PCR. Thus, PCV4 has an unclear association with clinical disease. This study utilized 512 porcine clinical lung, feces, spleen, serum, lymphoid tissue, and fetus samples submitted to the ISU-VDL from June-September 2023. PCV4 was detected in 8.6% of samples with an average Ct value of 33. While detection rates among sample types were variable, lymphoid tissue had the highest detection rate (18.7%). Two ORF2 sequences were obtained from lymphoid tissue samples and had 96.36-98.98% nucleotide identity with reference sequences. Direct detection of PCV4 by RNAscope revealed viral replication in B lymphocytes and macrophages in lymph node germinal centers and histiocytic and T lymphocyte infiltration in the lamina propria of the small intestine. PCV4 detection was most commonly observed in nursery to finishing aged pigs displaying respiratory and enteric disease. Coinfection with PCV2, PCV3, and other endemic pathogens was frequently observed, highlighting the complex interplay between different PCVs and their potential roles in disease pathogenesis. This study provides insights into the frequency of detection, tissue distribution, and genetic characteristics of PCV4 in the US.

Subchronic intranasal lipopolysaccharide exposure induces pulmonary autoimmunity and glomerulonephritis in NZBWF1 mice.

Lupus, a systemic autoimmune disease shaped by gene-environment interplay, often progresses to endstage renal failure. While subchronic systemic exposure to bacterial lipopolysaccharide (LPS) triggers autoimmunity and glomerulonephritis in lupus-prone mice, it is unknown if inhaling LPS, which is common in certain occupations, can similarly trigger lupus. Here we determined how subchronic intranasal (IN) LPS instillation influences autoimmunity and glomerulonephritis development in lupusprone NZBWF1 female mice. Briefly, mice were IN-instilled with vehicle or E. coli LPS (0.8 µg/g) twice weekly for 5 wk, followed by necropsy. For systemic comparison, additional cohorts of mice were injected with LPS intraperitoneally (IP) using identical doses/timing. Lungs were assessed for inflammatory and autoimmune responses and then related to systemic autoimmunity and glomerulonephritis. IN/LPS exposure induced in the lung: i) leukocyte infiltration, ii)mRNA signatures for cytokines, chemokines, IFN-regulated, and cell death-related genes, iii) ectopic lymphoid tissue formation, and iv)diverse IgM and IgG autoantibodies (AAbs). Pulmonary effects coincided with enlarged spleens, elevated plasma IgG AAbs, and inflamed IgG-containing kidney glomeruli. In contrast, IP/LPS treatment induced systemic autoimmunity and glomerulonephritis without pulmonary manifestations. Taken together, these preclinical findings suggest the lung could serve as a critical nexus for triggering autoimmunity by respirable LPS in genetically predisposed individuals.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue of the ileum in an adult presenting with intussusception: a case report and literature review.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL), also known as MALT lymphoma, is an extranodal multiorgan-invasive proliferative lymphoma composed of small B cells with variable morphology. It most commonly occurs in the digestive tract, with a high prevalence in the stomach, but EMZL originating in the small intestine is rare and lacks specificity in clinical manifestations, which makes it easy to be misdiagnosed. Herein, we report a rare case of small intestinal EMZL presentation as intussusception in a 32-year-old man. A colonoscopy performed at the local hospital revealed a pedicled polyp about 5 cm × 5 cm in size with a rough surface, and hyperemia was seen in the ileocecal region. He was admitted to our hospital for a polypectomy. A contrast-enhanced computed tomographic (CT) scan suggested ileocolic intussusception, which was subsequently confirmed by a colonoscopy in our hospital. Adult intussusception is relatively rare, with 90% of cases having a known causative mechanism and 40% of cases caused by primary or secondary malignancies. Therefore, we performed a laparoscopic-assisted right hemicolectomy for the patient. The resected specimen showed that the terminal ileum was intussuscepted into the ascending colon, and the intussusception was hyperemia and edema. A 2.5 cm × 2.5 cm × 1.5 cm mass was seen at the end of the intussusception. Postoperative pathology revealed that the mass was EMZL, partially transformed into a large B-cell lymphoma. The patient was transferred to the hematology department and completed a PET-CT showing postoperative manifestations of primary intestinal lymphoma, Lugano staging IE2. Although EMZL was an indolent lymphoma and the patient was in the early stages, the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen was given in view of the histological transformation. The patient is in regular follow-up. This was a rare case of small intestinal mass due to EMZL presented as intussusception in adults, which highlighted laparoscopic-assisted enterectomy as a potential therapeutic approach in the multidisciplinary collaborative therapy of small intestine EMZL.

Single-cell profiling indicates a high similarity between immune cells in the cerebrospinal fluid and in meningeal ectopic lymphoid tissue in experimental autoimmune encephalomyelitis.

Background and objectives: B cell depleting anti-CD20 monoclonal antibodies (aCD20 mAbs) are highly effective in treatment of multiple sclerosis (MS) but fail to halt the formation of meningeal ectopic lymphoid tissue (mELT) in the murine model experimental autoimmune encephalomyelitis (EAE). While mELT can be examined in EAE, it is not accessible in vivo in MS patients. Our key objectives were to compare the immune cells in cerebrospinal fluid (CSF), which is accessible in patients, with those in mELT, and to study the effects of aCD20 mAbs on CSF and mELT in EAE. Methods: Applying single cell RNA sequencing, we compared gene expression profiles in immune cells from (1) CSF with mELT and (2) aCD20 mAbs treated with control treated mice in a spontaneous 2D2xTh EAE model. Results: The immune cell composition in CSF and mELT was very similar. Gene expression profiles and pathway enrichment analysis revealed no striking differences between the two compartments. aCD20 mAbs led not only to a virtually complete depletion of B cells in the CSF but also to a reduction of naïve CD4+ T cells and marked increase of macrophages. No remarkable differences in regulated genes or pathways were observed. Discussion: Our results suggest that immune cells in the CSF may serve as a surrogate for mELT in EAE. Future studies are required to confirm this in MS patients. The observed increase of macrophages in B cell depleted CSF is a novel finding and requires verification in CSF of aCD20 mAbs treated MS patients. Due to unresolved technical challenges, we were unable to study the effects of aCD20 mAbs on mELT. This should be addressed in future studies.

Evaluation of PTV margin in CBCT-based online adaptive radiation therapy for gastric mucosa-associated lymphoid tissue lymphoma.

The aim of this study was to investigate planning target volume (PTV) margin in online adaptive radiation therapy (oART) for gastric mucosa-associated lymphoid tissue (MALT) lymphomas. Four consecutive patients with gastric MALT lymphoma who received oART (30 Gy in 15 fractions) on the oART system were included in this study. One hundred and twenty cone-beam computed tomography (CBCT) scans acquired pre- and post-treatment of 60 fractions for all patients were used to evaluate intra- and interfractional motions. Patients were instructed on breath-holding at exhalation during image acquisition. To assess the intrafraction gastric motion, different PTVs were created by isotropically extending the CTV contoured on a pre-CBCT image (CTVpre) at1 mm intervals. Intrafraction motion was defined as the amount of expansion covering the contoured CTV on post-CBCT images (CTVpost). Interfractional motion was defined as the amount of reference CTV expansion that could cover each CTVpre, as well as the evaluation of the intrafractional motion. PTV margins were estimated from the cumulative proportion of fraction covering the intra- and interfractional motions. The extent of expansion covering the CTVs in 90% of fractions was adopted as the PTV margin. The PTV margin for intrafractional gastric motion using the oART system with breath-holding was 14 mm. In contrast, the PTV margin for interfractional gastric organ motion without the oART system was 25 mm. These results indicated that the oART system can reduce the PTV margin by >10 mm. Our results could be valuable data for oART cases.

[Gastrointestinal mucosa-associated lymphoma]. / Mukosaassoziierte Lymphome des Gastrointestinaltrakts.

Mucosa-associated lymphomas of the gastrointestinal tract are a heterogeneous group differing in pathogenesis, localization and therapeutic options. For all of them, differentiated treatment requires an exact determination of lymphoma stage. For gastric MALT lymphoma, the pathogenetic role of Helicobacter pylori infection has become evident in the last 30 years. These insights were consequently implemented into clinical practice. Nowadays, Helicobacter pylori eradication is the treatment of choice for gastric MALT lymphoma, leading to complete remission of the lymphoma in the majority of cases. In the absence of success, radiotherapy is available in localized stages I/II E with excellent results. Immuno-chemotherapy is the domain for advanced stages III/IV E, and surgery plays no role any more. The rare intestinal and colorectal MALT lymphomas require an individualized therapeutic approach.

Clinicopathological characteristics of methotrexate-related lymphoproliferative disorder of the thyroid: A study of 11 patients.

Methotrexate (MTX) is a well-known agent that can potentially cause lymphoproliferative disorder (LPD), known as MTX-related LPD (MTX-LPD). Only two cases of thyroid MTX-LPD have been reported to date. This study aimed to report 11 cases of MTX-LPDs arising in the thyroid gland and discuss their clinicopathological characteristics. Of the 747 patients with cytologically suspected lymphoma, 11 had received MTX. The mean age of the patients with MTX-LPD was 70.2 years (range: 51-82 years), and all were female. The duration of MTX administration ranged from 5 to 31 years (mean: 19.5 years). Nine patients (81.8 %) tested positive for anti-thyroglobulin antibody and/or anti-thyroid peroxidase antibody. In three patients, the tumor decreased in size or disappeared without surgery or chemotherapy after withdrawal of MTX therapy. Histologically, all eight nodules examined were B-cell lymphomas, and seven were mucosa-associated lymphoid tissue (MALT) lymphomas. Epstein-Barr virus-encoded small RNA in situ hybridization showed negative results for all six nodules examined. All five patients who were followed-up at our hospital exhibited progression-free survival for >3 years without chemotherapy. Six patients were transferred to other hospitals, and their follow-up details are unknown. MTX-LPDs occurring in the thyroid are characterized by a high female predominance, positivity for anti-thyroid autoantibodies, high prevalence of MALT lymphomas, negativity for Epstein-Barr virus, and good outcomes without chemotherapy. We recommend that patients with thyroid lymphoma should be checked for a history of MTX.

The National Landscapes of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma: Stable Trends in Black Populations and Late-Stage Tumors.

BACKGROUND: Helicobacter pylori (H. Pylori) eradication has been the mainstream for preventing and treating gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Prior data showed disparities in eradication rates of H. Pylori between different populations. This can potentially impact the occurrence of gastric MALT lymphoma. There are limited data on the incidence and mortality rates and trends of gastric MALT lymphoma in the US. Therefore, the aim of the current study was to conduct a time-trend analysis of gastric MALT lymphoma incidence and mortality rates in different populations. METHODS: The incidence rates of gastric MALT lymphoma were calculated from the United States Cancer Statistics (USCS) database (which covers nearly 98% of the US population) between 2001-2020 and were age-adjusted to the standard 2000 US population using SEER*Stat software (version 8.4.3, national cancer institute "NCI"). Incidence-based mortality (IBM) rates, also age-adjusted to the standard 2000 US population, were calculated from the Surveillance Epidemiology and End Results (SEER) database. Tumor location was specified using ICD-O-3 codes C 160-C 169 with malignant behavior. Histopathology was specified using the ICD-O-3 code 9699. The rates were categorized by sex, age, race/ethnicity, and tumor stage at diagnosis. Age groups were older adults (aged 55 years or older) and younger adults (aged younger than 55 years). Race/ethnic groups included Non-Hispanic White (White), Non-Hispanic Black (Black), Hispanic, Non-Hispanic Asian/Pacific Islander (API), and Non-Hispanic American Indian/Alaska Native (AI/AN), as reported in the database. Stage at diagnosis included early stage (in situ and localized tumors) and late stage (regional and distant site tumors). Joinpoint Regression Software (version 5.0.2, NCI) using the weighted Bayesian Information Criteria method was used to generate time trends. Trends were reported as annual percentage change (APC) and average APC (AAPC). Parametric estimations were used with a two-sided t-test to evaluate the trends with a p-value cutoff at 0.05. RESULTS: There were 21,625 patients diagnosed with gastric MALT lymphoma in the US between 2001 and 2020. Overall, incidence rates were significantly decreasing over the study period (AAPC = -1.93). This decrease was seen in males (AAPC = -1.67) and in females (AAPC = -1.66) (Figure). When categorized by age groups, older adults also experienced a significant decrease in gastric MALT lymphoma incidence rates (AAPC = -1.66). While this was also seen in younger adults, the rates were decreasing at a slower pace (AAPC = -1.38). When categorizing the trends by race/ethnicity, incidence rates were significantly decreasing in White (AAPC = -2.09), Hispanic (AAPC = -1.61), and API (AAPC = -3.92) populations. However, the rates were stable among Blacks. While early-stage tumors experienced a significant decrease (AAPC = -1.10), the rates were stable for late-stage tumors. When evaluating mortality, there were 11,036 patients whose death was attributed to gastric MALT lymphoma between 2000 and 2020. IBM rates were decreasing in males (AAPC = -1.47), older adults (AAPC = -1.55), Whites (AAPC = -1.23), Hispanics (AAPC = -1.73), APIs (AAPC = -2.30), and early-stage tumors (AAPC = -1.08). On the other hand, IBM rates were stable in females, younger adults, Blacks, and late-stage tumors. DISCUSSION: An extensive nationwide data analysis encompassing nearly 98% of patients diagnosed with gastric MALT lymphoma in the US unveils a declining trend in the incidence of cancer overall over the past two decades. This decline is observed in both sexes and various age groups. When stratifying by race and ethnicity, this incidence has been decreasing in all populations except among Black individuals. While early-stage tumors have also demonstrated a significant decrease in incidence rates, late-stage tumors have shown no parallel decline. Mortality evaluation also revealed an improvement in most of the US population except among females, younger adults, Black individuals, and late-stage tumors. While the cause of our findings is unclear, it could be driven by disproportionate exposure to risk factors, including H. Pylori, and disparities in screening, management, and outcomes. Future studies are warranted to investigate factors contributing to worse outcomes of gastric MALT lymphoma, especially in the Black population.

Tips and tricks for a proper radiological assessment of abdominal and pelvic lymph nodes.

The assessment of lymph node dimensions is a commonly used criterion in analyzing lymphatic involvement related to inflammatory or neoplastic diseases. However, it is important to understand that the interpretation of lymph nodes goes beyond simply considering their size. A pathologic lymph node can present with enlarged dimensions, a heterogeneous appearance, increased cortex thickness, irregular contours, or a lobulated shape. In this context, it is essential to consider not only the dimensions but also the morphology, attenuation, and enhancement of lymph nodes on imaging exams. This article aims to demonstrate how characteristics of lymph nodes, beyond their size, can provide crucial insights that assist in diagnostic reasoning, focusing on computed tomography. By emphasizing different enhancement patterns, attenuation, and the potential contents related to these patterns, the study seeks to show how these features can indicate possible differential diagnoses and guide more accurate clinical assessments.

Investigating the shared genetic basis and causal relationships between mucosa-associated lymphoid tissue inflammation and psychiatric disorders.

Background: Chronic and acute inflammation of the mucosa-associated lymphoid tissue have been positively linked to the development of psychiatric disorders in observational studies. However, it remains unclear whether this association is causal. In the present study, we investigated this association, using as proxies genetically predicted tonsillectomy, appendectomy and appendicitis on psychiatric disorders including major depressive disorder (MDD), schizophrenia (SCZ), bipolar depression (BD) and anxiety (ANX) via a two-sample Mendelian randomization (MR) analysis. Methods: Genetic association summary statistics for tonsillectomy, appendectomy and appendicitis were sourced from FinnGen Consortium, comprising data from 342,000 participants. Genetic correlations between all exposures and outcome were calculated with Linkage Disequilibrium Score (LDSC) Regression analysis. MR estimates were then calculated to assess their impact on the risk of developing psychiatric disorders. Sensitivity analysis was employed to test for any directional pleiotropy. Results: Our results suggest that there is no direct causal association between tonsillectomy, appendectomy or appendicitis with a heightened risk for development of psychiatric disorders. The robustness of the results of the main MR analysis was further confirmed with additional sensitivity analyses. However, a moderate inverse genetic correlation was observed between tonsillectomy and MDD traits (rg=-0.39, p-value (P)=7.5x10-5). Conclusion: Our findings provide, for the first time, evidence that there is no causal association between tonsillectomy or appendectomy on subsequent vulnerability of developing psychiatric disorders. Future studies using larger sample size GWAS should focus on unraveling the confounding factors and mediators to investigate this relationship further.

Uncommon presentation of gastric mucosa-associated lymphoid tissue lymphoma in a 13-year-old girl: acute vomiting of blood as the initial symptom.

Introduction and importance: Extranodal marginal zone lymphoma (EMZL lymphoma), also known as mucosa-associated lymphoid tissue (MALT) lymphoma, is a rare B-cell lymphoma that rarely affects children. The involvement of infectious agents, especially H. pylori, has been observed in the formation and progression of MALT lymphoma in the stomach. Hematemesis as the primary clinical manifestation is uncommon, highlighting the need for case studies with this presentation. This article uses SCARE2023 criteria as a framework to sort out a case report in order. Case presentation: A 13-year-old female patient was admitted in August 2022 with an episode of hematemesis. She had a prior diagnosis of anaemia and was found positive for H. pylori. Despite treatment, she developed symptoms of chronic non-atrophic gastritis and had recurring episodes of hematemesis. Physical and diagnostic examinations revealed B-cell lymphoma localized in the gastric antrum. The primary diagnosis was extranodal MALT lymphoma with unique plasma cell differentiation. Clinical discussion: The presentation of gastric MALT lymphoma can be variable, with definitive diagnosis often achieved via endoscopic biopsy. H. pylori plays a significant role in the onset and progression of this lymphoma, emphasizing the importance of its eradication for treatment. Effective outcomes can be achieved through anti-H. pylori treatment, although it is essential for clinicians to ensure its complete eradication post-treatment. Conclusion: Paediatric presentation of gastric MALT lymphoma, especially with hematemesis as the primary symptom, is rare and can be easily misdiagnosed. Compared to adults, children generally exhibit a better prognosis with effective H. pylori treatment. It is vital for medical professionals to recognize the differences in presentation between children and adults to ensure accurate diagnosis and treatment.

A case of pulmonary primary MALT lymphoma with distinctive bronchoscopic findings.

Mucosa-associated lymphoid tissue (MALT) is a low-grade lymphoma, but cases in which it has transformed into a high-grade lymphoma have been reported, necessitating an accurate diagnosis. The patient was a 79-year-old nonsmoking Japanese female with history of ocular sarcoidosis. A computed tomography scan of her chest revealed a 35-mm nodule in the left S1 + 2, contiguous with the lymph nodes. Additional nodules were observed around the left B5 and B10a. Bronchoscopy revealed stenosis caused by a white, glossy, elevated lesion with angiogenesis at the orifice of the left upper lobe bronchus. The biopsy specimen demonstrated the dominance of lymphoid cells and tested positive for CD20, CD79a, Bcl-2, and IRTA-1, which is consistent with the findings in MALT lymphoma. Therefore, in the presence of multiple infiltrative shadows along the bronchi with glossy elevated lesions without necrosis on bronchoscopy, it is important to consider MALT lymphoma as a differential diagnosis.

Inhibition of caspase pathways limits CD4+ T cell loss and restores host anti-retroviral function in HIV-1 infected humanized mice with augmented lymphoid tissue.

The study of HIV infection and pathogenicity in physical reservoirs requires a biologically relevant model. The human immune system (HIS) mouse is an established model of HIV infection, but defects in immune tissue reconstitution remain a challenge for examining pathology in tissues. We utilized exogenous injection of the human recombinant FMS-like tyrosine kinase 3 ligand (rFLT-3 L) into the hematopoietic stem cell (HSC) cord blood HIS mouse model to significantly expand the total area of lymph node (LN) and the number of circulating human T cells. The results enabled visualization and quantification of HIV infectivity, CD4 T cell depletion and other measures of pathogenesis in the secondary lymphoid tissues of the spleen and LN. Treatment with the Caspase-1/4 inhibitor VX-765 limited CD4+ T cell loss in the spleen and reduced viral load in both the spleen and axillary LN. In situ hybridization further demonstrated a decrease in viral RNA in both the spleen and LN. Transcriptomic analysis revealed that in vivo inhibition of caspase-1/4 led to an upregulation in host HIV restriction factors including SAMHD1 and APOBEC3A. These findings highlight the use of rFLT-3 L to augment human immune system characteristics in HIS mice to support investigations of HIV pathogenesis and test host directed therapies, though further refinements are needed to further augment LN architecture and cellular populations. The results further provide in vivo evidence of the potential to target inflammasome pathways as an avenue of host-directed therapy to limit immune dysfunction and virus replication in tissue compartments of HIV+ persons.

Mucosa-Associated Lymphoid Tissue Surgeries as a Possible Risk for Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Background: Inflammatory bowel disease (IBD) is a group of chronic inflammatory gastrointestinal disorders that are caused by genetic susceptibility and environmental factors and affects a significant portion of the global population. The gut-associated lymphoid tissue (GALT) is known to play a crucial role in immune modulation and maintaining gut microbiota balance. Dysbiosis in the latter has a known link to IBD. Therefore, the increasing prevalence of adenoidectomy in children should be explored for its potential association with IBD. The objective of this paper was to assess the association between adenoid tissue removal and the risk of developing Crohn's disease (CD) and ulcerative colitis (UC). Methods: We conducted a pooled meta-analysis to evaluate the extended clinical outcomes in patients who underwent appendicectomy and tonsillectomy compared to those who did not. Our approach involved systematically searching the PubMed database for relevant observational studies written in English. We followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines to collect data from various time periods, and to address the diversity in study results; we employed a random-effects analysis that considered heterogeneity. For outcomes, odds ratios (ORs) were pooled using a random-effects model. Results: Seven studies, out of a total of 114,537, met our inclusion criteria. Our meta-analysis revealed a significant association between appendicectomy and CD (OR: 1.57; 95% confidence interval (CI): 1.01 - 2.43; heterogeneity I2 = 93%). Similarly, we found a significant association between tonsillectomy and CD (OR: 1.93; 95% CI: 0.96 - 3.89; I2 = 62%). However, no significant association was observed between appendicectomy and UC (OR: 0.60; 95% CI: 0.24 - 1.47; I2 = 96%), while a modest association was found between tonsillectomy and UC (OR: 1.24; 95% CI: 1.18 - 1.30; I2 = 0%). Conclusions: In summary, we found that the trend of appendicectomy is linked to higher odds of CD, and tonsillectomy is more likely associated with increased odds for both CD and UC, with a risk of bias present.

Definitive Radiotherapy for Stage I Gastric Mucosa-Associated Lymphoid Tissue Lymphoma: A Retrospective Cohort of Unique-Dose Administration of 30 Gy in 15 Fractions and Analysis of Remission Duration.

Background: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma constitutes a significant proportion of primary stomach lymphomas. The optimal dosage for radiotherapy and standardized follow-up protocols are yet to be universally established. This study focuses on stage I gastric MALT lymphoma patients, presenting clinical outcomes of radiotherapy with a unique dose of 30 Gy in 15 fractions and analyzing remission time. Methods: A retrospective cohort study, approved by the institutional review board, included consecutive stage I gastric MALT lymphoma patients undergoing curative radiotherapy between 2008 and 2022. Staging followed the Lugano Modification of the Ann Arbor Staging System. The prescribed dose was uniform dose of 30 Gy in 15 fractions. Results: Fifty-three patients were eligible, with a median age of 63 years. All achieved complete remission (CR), with a median CR time of 3.9 months. At a median follow-up of 56.8 months, no deaths occurred, and three recurrences were noted. The 5-year overall survival, local control survival, and disease-free survival rates were 100%, 100%, and 97.7%, respectively. No severe acute adverse events were observed. Conclusion: The study demonstrates sustained and favorable long-term disease control with a 30 Gy dose in 15 fractions for stage I gastric MALT lymphoma. Comparisons with existing literature highlight the efficacy and safety of radiotherapy in achieving durable remission. Ongoing efforts explore dose reduction and technological advancements to minimize toxicity. This study emphasizes the importance of awaiting clinical response confirmation to validate these outcomes in patients with gastric MALT lymphoma.

Tubulointerstitial nephritis with IgG4-positive plasma cell infiltration and tertiary lymphoid tissue in a patient with cryoglobulinemic vasculitis: a case report.

Tertiary lymphoid tissue (TLT) develops at sites of chronic immune stimulation, including infection, autoimmune disease, transplant rejection, and cancer. Recently, TLT has been focused on an indicator for poor renal prognosis in various kidney diseases. In cryoglobulinemic vasculitis (CV), specific glomerular and vascular lesions are seen; however, tubulointerstitial lesions are usually nonspecific. We herein report the case of a 74-year-old man with idiopathic CV with rare tubulointerstitial lesions, such as tubulointerstitial nephritis (TIN) with IgG4-positive plasma cell infiltration and TLT. To our knowledge, this is the first report identifying TLT in the kidney biopsy in a patient with CV. Glucocorticoid improved the renal outcome. The association between CV and TIN with TLT remains unknown.

Spontaneous regression and rare relapse after excisional biopsy in long-term observation of 31 patients with primary conjunctival lymphoma.

To elucidate long-term outcome in primary conjunctival lymphoma, a review was conducted of 31 consecutive patients: 21 men and 10 women with an age range of 28 to 85 (median, 61) years at presentation and follow-up periods ranging from 1 to 19 (median, 7) years. Conjunctival lymphoma was on the right side in 10 patients, on the left side in 12, and on both sides in 9. Upper, lower, or both fornix lesions in 28 patients were all diagnosed as extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), while thick nasal bulbar conjunctival lesions in 3 patients were differently diagnosed as MALT lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma, respectively. Seven patients underwent local radiation (30 Gy): as initial treatment in 5 patients and treatment for relapse in 2 patients. The remaining 24 patients were observed without additional treatment after excisional biopsy: 5 of these 24 patients showed relapse 0.5 to 6 years later and underwent excisional biopsy again that revealed MALT lymphoma. Of the 5 patients with relapse, only one with second-time relapse underwent radiation. Fluorodeoxyglucose positron emission tomography was performed in 18 patients and showed no systemic lesions: high uptake was noted in the residual conjunctival lesions of 4 patients and in the relapsed conjunctival lesions of 3 patients. One patient died of rectal cancer while no patients died of lymphoma. Observation is an option in patients with primary conjunctival lymphoma after excisional biopsy. Radiation is a treatment option in the case of relapse.

Immunohistochemistry of the nasal cavity-associated lymphoid tissue in the dolphin (Stenella coeruleoalba, Meyen 1833).

The striped dolphin (Stenella coeruleoalba) is a medium-sized pelagic dolphin with a single external nasal opening (blowhole) located in the rostral and dorsal regions of the skull. The nasal cavity is divided into three sections: the olfactory, respiratory, and vestibular areas. The surface epithelium lining the regio vestibularis is the first tissue in the nose to be directly affected by environmental antigens. Cetaceans have a significant amount of mucosa-associated lymphoid tissue (MALT) located throughout their bodies. The lymphoid tissue found in the nasal mucosa is known as nose- or nasopharynx-associated lymphoid tissue (NALT). NALT has not yet been studied in dolphins, but it has been identified and documented in humans and laboratory rodents. This study utilized toll-like receptor 2 (TLR2), CD4, Langerin/CD207, and inducible nitric oxide synthase to characterize, for the first time, immune cells in the mucosal regio vestibularis of the S. coeruleoalba nasal cavity using confocal microscopy immunofluorescence techniques. The findings revealed scattered immune cells immunoreactive to the tested antibodies, present in both the epithelial tissue lining the nasal cavity vestibulum and the underlying connective tissue. This study enhances our comprehension of the immune system of cetaceans. RESEARCH HIGHLIGHTS: This study provides new insights into NALT in S. coeruleoalba. This research deepens the knowledge of the skin of cetaceans.