CT radiomics analysis discriminates pulmonary lesions in patients with pulmonary MALT lymphoma and non-pulmonary MALT lymphoma.

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.

Cellular and molecular diversity in Sjogren's syndrome salivary glands: Towards a better definition of disease subsets.

Primary Sjögren's syndrome (pSS) is a highly heterogeneous disease in terms of clinical presentation ranging from a mild disease localised to the salivary and lacrimal glands, to multiorgan complications of various degrees of severity, finishing with the evolution, in around 5% of pSS patients, to B cell lymphomas most commonly arising in the inflamed salivary glands. Currently, there are poor positive or negative predictors of disease evolution able to guide patient management and treatment at early stages of the diseases. Recent understanding of the pathogenic mechanisms driving immunopathology in pSS, particularly through histological and transcriptomic analysis of minor and parotid salivary gland (SG) biopsies, has highlighted a high degree of cellular and molecular heterogeneity of the inflammatory lesions but also allowed the identification of clusters of patients with similar underlying SG immunopathology. In particular, patients presenting with high degrees of B/T cell infiltration and the formation of ectopic lymphoid structures (ELS) in the SG have been associated, albeit with conflicting results, with higher degree of disease severity and enhanced risk of lymphoma evolution, suggesting that a dysregulated adaptive immune response plays a key role in driving disease manifestations in pSS. Recent data from randomised clinical trials with novel biological therapies in pSS have also highlighted the potential role of SG immunopathology and molecular pathology in stratifying patients for trial inclusion as well as assessing proof of mechanisms in longitudinal SG biopsies before and after treatment. Although significant progress has been made in the understanding of disease pathogenesis and heterogeneity through cellular and molecular SG pathology, further work is needed to validate their clinical utility in routine clinical settings and in randomised clinical trials.

Paracaspase MALT1 regulates glioma cell survival by controlling endo-lysosome homeostasis.

Glioblastoma is one of the most lethal forms of adult cancer with a median survival of around 15 months. A potential treatment strategy involves targeting glioblastoma stem-like cells (GSC), which constitute a cell autonomous reservoir of aberrant cells able to initiate, maintain, and repopulate the tumor mass. Here, we report that the expression of the paracaspase mucosa-associated lymphoid tissue l (MALT1), a protease previously linked to antigen receptor-mediated NF-κB activation and B-cell lymphoma survival, inversely correlates with patient probability of survival. The knockdown of MALT1 largely impaired the expansion of patient-derived stem-like cells in vitro, and this could be recapitulated with pharmacological inhibitors, in vitro and in vivo. Blocking MALT1 protease activity increases the endo-lysosome abundance, impairs autophagic flux, and culminates in lysosomal-mediated cell death, concomitantly with mTOR inactivation and dispersion from endo-lysosomes. These findings place MALT1 as a new druggable target involved in glioblastoma and unveil ways to modulate the homeostasis of endo-lysosomes.

Novel identification of t(14;18)(q32;q21)/IGH::MALT1 in chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is a clonal B-cell malignancy and remains a chronic disease despite improvements in clinical outcomes since the use of targeted therapies. Both clinical and biological parameters are important for determining prognosis. Unlike other mature B-cell lymphomas, translocations involving the immunoglobulin heavy chain (IGH) locus are uncommon in CLL. There have been few case reports of CLL harbouring t(14;18)/IGH::BCL2 and t(14;19)/IGH::BCL3. Here we describe the first two cases of patients with CLL with documented t(14;18)(q32;q21)/IGH::MALT1. Both cases in this report were associated with lower-risk biological parameters. Thus, FISH testing for MALT1 in cases with unknown IGH translocation partners in the setting of CLL should be implemented in clinical practice to better define such cases.

Study of individual domains contributing to MALT1 dimerization in BCL10-independent and dependent assembly.

The CARMA-BCL10-MALT1 (CBM) signalosome functions as a pivotal supramolecular module, integrating diverse receptor-induced signaling pathways to regulate BCL10-dependent NF-kB activation in innate and adaptive immunity. Conversely, the API2-MALT1 fusion protein in t(11; 18)(q21; q21) MALT lymphoma constitutively induces BCL10-independent NF-kB activation. MALT1 dimer formation is indispensable for the requisite proteolytic activity and is critical for NF-kB activation regulation in both scenarios. However, the molecular assembly of MALT1 individual domains in CBM activation remains elusive. Here we report the crystal structure of the MALT1 death domain (DD) at a resolution of 2.1 Å, incorporating reconstructed residues in previously disordered loops 1 and 2. Additionally, we observe a conformational regulation element (CRE) regulating stem-helix formation in NLRPs pyrin (PYD) within the MALT1 DD structure. The structure reveals a stem-helix-mediated dimer further corroborated in solution. To elucidate how the BCL10 filament facilitates MALT1 dimerization, we reconstitute a BCL10-CARD-MALT1-DD-IG1-IG2 complex model. We propose a N+7 rule for BCL10-dependent MALT1 dimerization via the IG1-IG2 domain and for MALT1-dependent cleavage in trans. Biochemical data further indicates concentration-dependent dimerization of the MALT1 IG1-IG2 domain, facilitating MALT1 dimerization in BCL10-independent manner. Our findings provide a structural and biochemical foundation for understanding MALT1 dimeric mechanisms, shedding light on potential BCL10-independent MALT1 dimer formation and high-order BCL10-MALT1 assembly.

Primary MALT lymphoma of the breast: pathological and radiological characteristics.

PURPOSE: Primary Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare diagnosis in the breast, and clinical diagnosis based on radiological features is often challenging. This study aimed to evaluate the clinicopathological, and radiological characteristics of the patients diagnosed with primary breast MALT lymphoma. METHODS: This study examined 18 cases of primary MALT lymphoma of the breast diagnosed at a single tertiary center between January 2002 to December 2020. Medical charts, radiological imaging and original pathology slides were reviewed for each case. RESULTS: All cases were female (gender assigned at birth) and presented with a palpable mass or an incidental imaging finding. Imaging presentation ranged from mammographic asymmetries, circumscribed masses, and ultrasound masses lacking suspicious features. Seventeen cases were biopsied under ultrasound; one received a diagnostic excision biopsy. Microscopic examination of the breast specimens demonstrated atypical small lymphocyte infiltration with plasmacytoid differentiation and rare lymphoepithelial lesions. Immunohistochemistry was performed in all cases and established the diagnosis. Most patients were treated with radiotherapy, and only three were treated with chemotherapy. The median follow-up period was 4 years and 7.5 months, and all patients were alive at the last follow-up. CONCLUSION: Primary MALT breast lymphomas are usually indolent and non-systemic, and local radiotherapy may effectively alleviate local symptoms. Radiological findings show overlap with benign morphological features, which can delay the diagnosis of this unusual etiology. Although further studies involving a larger cohort could help establish the clinical and radiological characteristics of primary breast MALT lymphomas, pathology remains the primary method of diagnosis. TRIAL REGISTRATION NUMBER: University Health Network Ethics Committee (CAPCR/UHN REB number 19-5844), retrospectively registered.

MALT1 inhibition suppresses antigen-specific T cell responses.

The aim of this study was to assess the potential use of a selective small molecule MALT1 inhibitor in solid tumor treatment as an immunotherapy targeting regulatory T-cells (Tregs). In vitro, MALT1 inhibition suppressed the proteolytic cleavage of the MALT1-substrate HOIL1 and blocked IL-2 secretion in Jurkat cells. It selectively suppressed the proliferation of PBMC-derived Tregs, with no effect on conventional CD4+T-cells. In vivo, however, no evident anti-tumor effect was achieved by MALT1 inhibition monotherapy or in combination with anti-CTLA4 in the MB49 cancer model. Despite decreased Treg-frequencies in lymph nodes of tumor-bearing animals, intratumoral Treg depletion was not observed. We also showed that MALT1-inhibition caused a reduction of antigen-specific CD8+T-cells in an adoptive T-cell transfer model. Thus, selective targeting of Tregs would be required to improve the immunotherapeutic effect of MALT1-inhibition. Also, various dosing schedules and combination therapy strategies should be carefully designed and evaluated further.

Insights into the molecular mechanisms of H. pylori-associated B-cell lymphoma.

Cancer research has extensively explored various factors contributing to cancer development, including chemicals, drugs, smoking, and obesity. However, the role of bacterial infections in cancer induction remains underexplored. In particular, the mechanisms underlying H. pylori-induced B-cell lymphoma, a potential consequence of bacterial infection, have received little attention. In recent years, there has been speculation about contagious agents causing persistent inflammation and encouraging B-lymphocyte transition along with lymphomagenesis. MALT lymphoma associated with chronic H. pylori infection, apart from two other central associated lymphomas - Burkitt's Lymphoma and DLBCL, is well studied. Owing to the increasing colonization of H. pylori in the host gut and its possible action in the development of B-cell lymphoma, this review aims to summarize the existing reports on different B-cell lymphomas' probable association with H. pylori infections; also emphasizing the function of the organism in lymphomagenesis; including its interaction with the host, pathogen and host-specific factors, and tumor microenvironment.

The role of baseline 2-[18 F]-FDG-PET/CT metrics and radiomics features in predicting primary gastric lymphoma diagnosis.

Diffuse Large B-Cell Lymphomas (DLCBL) and mucosa-associated lymphoid tissue (MALT) are the two most common primary gastric lymphomas (PGLs), but have strongly different features. DLBCL is more aggressive, is frequently diagnosed at an advanced stage and has a poorer prognosis. The aim of this retrospective study was to explore the role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (2-[18 F]-FDG-PET/CT) and radiomics features (RFs) in predicting the final diagnosis of patients with PGLs. Ninety-one patients with newly diagnosed PGLs who underwent pre-treatment 2-[18 F]-FDG-PET/CT were included. PET images were qualitatively and semi-quantitatively analyzed by deriving maximum standardized uptake value body weight (SUVbw), maximum standardized uptake value lean body mass (SUVlbm), maximum standardized uptake value body surface area (SUVbsa), lesion to liver SUVmax ratio (L-L SUV R), lesion to blood-pool SUVmax ratio (L-BP SUV R), metabolic tumor volume (gMTV) and total lesion glycolysis of gastric lesion (gTLG), total MTV (tMTV), TLG, and first-order RFs (histogram-related and shape related). Receiver-operating characteristic (ROC) curve analyses were performed to determine the differential diagnostic values of PET parameters. The final diagnosis was DLBCL in 54 (59%) cases and MALT in 37 cases (41%). PGLs showed FDG avidity in 83 cases (90%), 54/54 of DLBCL and 29/37 of MALT. All PET/CT metabolic features, such as stage of disease and tumor size, were significantly higher in DLBCL than MALT; while the presence of H. Pylori infection was more common in MALT. At univariate analysis, all PET/CT metrics were significantly higher in DLBCL than MALT lymphomas, while among RFs only Shape volume_vx and Shape sphericity showed a significant difference between the two groups. In conclusion we demonstrated that 2-[18 F]-FDG-PET/CT parameters can potentially discriminate between DLBCL and MALT lymphomas with high accuracy. Among first-order RFs, only Shape volume_vx and Shape sphericity helped in the differential diagnosis.

Inhibition of the MALT1-LPCAT3 axis protects cartilage degeneration and osteoarthritis.

The proinflammatory cytokines and arachidonic acid (AA)-derived eicosanoids play a key role in cartilage degeneration in osteoarthritis (OA). The lysophosphatidylcholine acyltransferase 3 (LPCAT3) preferentially incorporates AA into the membranes. Our recent studies showed that MALT1 [mucosa-associated lymphoid tissue lymphoma translocation protein 1]) plays a crucial role in propagating inflammatory signaling triggered by IL-1ß and other inflammatory mediators in endothelial cells. The present study shows that LPCAT3 expression was up-regulated in both human and mice articular cartilage of OA, and correlated with severity of OA. The IL-1ß-induces cell death via upregulation of LPCAT3, MMP3, ADAMTS5, and eicosanoids via MALT1. Gene silencing or pharmacological inhibition of LPCAT3 or MALT1 in chondrocytes and human cartilage explants notably suppressed the IL-1ß-induced cartilage catabolism through inhibition of expression of MMP3, ADAMTS5, and also secretion of cytokines and eicosanoids. Mechanistically, overexpression of MALT1 in chondrocytes significantly upregulated the expression of LPCAT3 along with MMP3 and ADAMTS5 via c-Myc. Inhibition of c-Myc suppressed the IL-1ß-MALT1-dependent upregulation of LPCAT3, MMP3 and ADAMTS5. Consistent with the in vitro data, pharmacological inhibition of MALT1 or gene silencing of LPCAT3 using siRNA-lipid nanoparticles suppressed the synovial articular cartilage erosion, pro-inflammatory cytokines, and eicosanoids such as PGE2, LTB4, and attenuated osteoarthritis induced by the destabilization of the medial meniscus in mice. Overall, our data reveal a previously unrecognized role of the MALT1-LPCAT3 axis in osteoarthritis. Targeting the MALT1-LPCAT3 pathway with MALT1 inhibitors or siRNA-liposomes of LPCAT3 may become an effective strategy to treat OA by suppressing eicosanoids, matrix-degrading enzymes, and proinflammatory cytokines.

The COP9 signalosome stabilized MALT1 promotes Non-Small Cell Lung Cancer progression through activation of NF-κB pathway.

MALT1 has been implicated as an upstream regulator of NF-κB signaling in immune cells and tumors. This study determined the regulatory mechanisms and biological functions of MALT1 in non-small cell lung cancer (NSCLC). In cell culture and orthotopic xenograft models, MALT1 suppression via gene expression interference or protein activity inhibition significantly impaired malignant phenotypes and enhanced radiation sensitivity of NSCLC cells. CSN5, the core subunit of COP9 signalosome, was firstly verified to stabilize MALT1 via disturbing the interaction with E3 ligase FBXO3. Loss of FBXO3 in NSCLC cells reduced MALT1 ubiquitination and promoted its accumulation, which was reversed by CSN5 interference. An association between CSN5/FBXO3/MALT1 regulatory axis and poor prognosis in NSCLC patients was identified. Our findings revealed the detail mechanism of continuous MALT1 activation in NF-κB signaling, highlighting its significance as predictor and potential therapeutic target in NSCLC.

Endoscopic morphology of gastric MALT lymphoma correlate with API2/MALT1 fusion and predict treatment response after helicobacter pylori eradication.

BACKGROUND: The presence of API2/MALT1 fusion in gastric mucosa-associated lymphoid tissue (MALT) lymphoma predicts poor response to Helicobacter pylori (Hp) eradication therapy. This study aimed to assess the correlation between endoscopic morphology of MALT lymphoma and API2/MALT1 fusion and evaluate treatment response to Hp eradication based on morphological subtypes. METHODS: A retrospective review was conducted on patients diagnosed with gastric MALT lymphoma between January 2011 and December 2022. Endoscopic morphology was categorized as superficial, non-superficial, or mixed type. The superficial type was further classified into gastritis superficial lesion and localized superficial lesion based on border clarity. Logistic regression models evaluated the impact of clinical and endoscopic characteristics on anti-Hp therapy effectiveness. RESULTS: Among the 114 patients included, 93 (81.6%) were Hp-positive, and API2/MALT1 fusion was detected in 58 (50.9%) cases, The superficial type was the predominate morphology (73/114, 64%). The regular arrangement of collecting venules (RAC) sign was noted in 21 (18.4%) cases. In superficial subtypes, the RAC signs were more frequently observed in localized lesion than gastritis lesion (35.6% vs. 7.1%, p = 0.01). and the superficial localized lesion was more common in individuals with positive API/MALT1 fusion than negative ones (76.9% vs. 44.1%, p = 0.01). Following Hp eradication, the remission rate for localized lesion was 34.3%, significantly lower than for gastritis lesion (66.7%, p = 0.01). Both endoscopic morphology (OR = 0.26, 95% CI 0.09-0.75) and API2-MALT1 fusion (OR = 14.29, 95% CI 4.19-48.67) impacted the efficacy of anti-Hp therapy. However, multivariate analysis identified API2-MALT1 fusion as the only independent predictor of treatment outcome (OR = 12.18, 95% CI 3.49-42.55, p < 0.001). CONCLUSION: Gastric MALT lymphomas with superficial-type morphology, particularly those with defined borders resembling early gastric cancer, were associated with API2/MALT1 fusion and a lower remission rate after Hp eradication therapy. This suggests that endoscopic morphology, along with API2/MALT1 fusion status, could help predict the therapeutic response, with API2/MALT1 fusion serving as a critical indicator of treatment resistance.

Lymphoma-associated mutations in autoreactive memory B cells of patients with Sjögren's syndrome.

We recently demonstrated that normal memory B lymphocytes carry a substantial number of de novo mutations in the genome. Here, we performed exome-wide somatic mutation analyses of bona fide autoreactive rheumatoid factor (RF)-expressing memory B cells retrieved from patients with SjÓ§gren's syndrome (SS). The amount and repertoire of the de novo exome mutations of RF B cells were found to be essentially different from those detected in healthy donor memory B cells. In contrast to the mutation spectra of normal B cells, which appeared random and non-selected, the mutations of the RF B cells were greater in number and enriched for mutations in genes also found mutated in B-cell non-Hodgkin lymphomas. During the study, one of the SS patients developed a diffuse large B-cell lymphoma (DLBCL) out of an RF clone that was identified 2 years earlier in an inflamed salivary gland biopsy. The successive oncogenic events in the RF precursor clone and the DLBCL were assessed. In conclusion, our findings of enhanced and selected genomic damage in growth-regulating genes in RF memory B cells of SS patients together with the documented transformation of an RF-precursor clone into DLBCL provide unique novel insight into the earliest stages of B-cell derailment and lymphomagenesis. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Anti-CD40L therapy prevents the formation of precursor lesions to gastric B-cell MALT lymphoma in a mouse model.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a B-cell tumour that develops over many decades in the stomachs of individuals with chronic Helicobacter pylori infection. We developed a new mouse model of human gastric MALT lymphoma in which mice with a myeloid-specific deletion of the innate immune molecule, Nlrc5, develop precursor B-cell lesions to MALT lymphoma at only 3 months post-Helicobacter infection versus 9-24 months in existing models. The gastric B-cell lesions in the Nlrc5 knockout mice had the histopathological features of the human disease, notably lymphoepithelial-like lesions, centrocyte-like cells, and were infiltrated by dendritic cells (DCs), macrophages, and T-cells (CD4+ , CD8+ and Foxp3+ ). Mouse and human gastric tissues contained immune cells expressing immune checkpoint receptor programmed death 1 (PD-1) and its ligand PD-L1, indicating an immunosuppressive tissue microenvironment. We next determined whether CD40L, overexpressed in a range of B-cell malignancies, may be a potential drug target for the treatment of gastric MALT lymphoma. Importantly, we showed that the administration of anti-CD40L antibody either coincident with or after establishment of Helicobacter infection prevented gastric B-cell lesions in mice, when compared with the control antibody treatment. Mice administered the CD40L antibody also had significantly reduced numbers of gastric DCs, CD8+ and Foxp3+ T-cells, as well as decreased gastric expression of B-cell lymphoma genes. These findings validate the potential of CD40L as a therapeutic target in the treatment of human gastric B-cell MALT lymphoma. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Intraoral primary syphilis mimicking lymphoproliferative disorder.

Syphilis can mimic, clinically and microscopically, many other diseases. By microscopy, typically syphilis presents with plasma cell infiltration, admixed with lymphocytes and macrophages, in lichenoid and/or perivascular/perineural distribution pattern. When exuberant, this inflammatory infiltrate can mimic a lymphoproliferative disorder (LPD), notably plasma cell neoplasia or lymphoma. To date, about 12 cases of secondary syphilis, all but one in extraoral location, suggesting initially a LPD, have been published. Here, to our knowledge, we report an unusual case of intraoral primary syphilis initially suggesting LPD, notably lymphoid hyperplasia (pseudolymphoma); however, mucosa-associated lymphoid tissue (MALT) lymphoma and follicular lymphoma could not be disregarded. Polyclonality of plasma cells on immunohistochemistry, in strict clinical correlation, was essential to arrive at the correct diagnosis.

An Unusual Case of Extranodal Marginal Zone Lymphoma Mimicking Abdominal Cocoon Syndrome in an Adolescent Patient.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is an indolent non-Hodgkin lymphoma rarely seen in pediatric patients. MALT lymphoma most commonly involves the gastrointestinal tract or peri-orbital tissues, potentially as sequela of chronic antigenic stimulation or immune dysregulation. Rare cases of MALT lymphoma arising from the gynecologic tract have been reported in older adult patients. We present the unique case of a 16-year-old postpubescent female with MALT lymphoma localized to the gynecologic tract, who initially presented with abdominal fullness, abnormal uterine bleeding, and obstructive acute kidney injury secondary to urinary outflow obstruction. Intraoperatively, dense fibrosis of the uterus and left fallopian tube was noted which mimicked abdominal cocoon syndrome. She was treated with 6 cycles of bendamustine and rituximab with complete anatomic and metabolic remission. In this report we highlight a very unusual presentation of a rare malignancy in the pediatric population as well as unique treatment considerations given this patient's young age and tumor location.

Artificial intelligence-based differential diagnosis of orbital MALT lymphoma and IgG4 related ophthalmic disease using hematoxylin-eosin images.

PURPOSE: To investigate the possibility of distinguishing between IgG4-related ophthalmic disease (IgG4-ROD) and orbital MALT lymphoma using artificial intelligence (AI) and hematoxylin-eosin (HE) images. METHODS: After identifying a total of 127 patients from whom we were able to procure tissue blocks with IgG4-ROD and orbital MALT lymphoma, we performed histological and molecular genetic analyses, such as gene rearrangement. Subsequently, pathological HE images were collected from these patients followed by the cutting out of 10 different image patches from the HE image of each patient. A total of 970 image patches from the 97 patients were used to construct nine different models of deep learning, and the 300 image patches from the remaining 30 patients were used to evaluate the diagnostic performance of the models. Area under the curve (AUC) and accuracy (ACC) were used for the performance evaluation of the deep learning models. In addition, four ophthalmologists performed the binary classification between IgG4-ROD and orbital MALT lymphoma. RESULTS: EVA, which is a vision-centric foundation model to explore the limits of visual representation, was the best deep learning model among the nine models. The results of EVA were ACC = 73.3% and AUC = 0.807. The ACC of the four ophthalmologists ranged from 40 to 60%. CONCLUSIONS: It was possible to construct an AI software based on deep learning that was able to distinguish between IgG4-ROD and orbital MALT. This AI model may be useful as an initial screening tool to direct further ancillary investigations.

Histopathologic clues to the etiopathogenesis of orbital inflammatory disease: Idiopathic, IgG4-related, neoplastic, autoimmune and beyond.

Orbital inflammatory diseases represent a heterogenous group of idiopathic, autoimmune-related, and sometimes neoplastic conditions with overlapping clinical and histopathologic features, as well as variable levels of IgG4-positive plasma cells detected within tissue biopsies. Some histopathologic features, especially in an appropriate clinical context, may point to a specific diagnosis in a given patient. Diagnoses of non-specific orbital inflammation, orbital inflammation related to autoimmune diseases such as granulomatosis with polyangiitis and IgG4-related disease, lymphoma, and xanthogranulomatous diseases are discussed, contrasted and illustrated.

Evaluation of kikuyu grass wetland for wastewater treatment efficiency from malt factory, Ethiopia.

BACKGROUND: The majority of existing industries in Ethiopia discharge untreated effluents into nearby water bodies, streams and open land. The wastewater generated by Gondar malt factory (GMF) was disposed freely and join a natural wetland implemented for the treatment of the wastewater. The objective of the study was to analyze and characterize wastewater from GMF and to evaluate the effectiveness of the wetland for the treatment purpose. METHODS: Different Physicochemical quality indicators (color, turbidity pH, temperature, Total Dissolved solids, Total Suspended solids, total solid, conductivity, alkalinity, hardness, nitrate, phosphate, sulfate, free chlorides, heavy metals-(Cd, Cr, Fe, Mn, and Pb)and Biological Oxygen Demand were measured according to the standard procedures. Data was analyzed using Statistical Package for Social Sciences (SPSS-25). Analysis of Variance (ANOVA) was used to find whether significant differences existed in the different sampling stations for the parameters studied. P value less than 0.05 was considered to show significant difference. RESULTS: The results of this study revealed that most of the quality indicators were improved in value after the water passed through the wetland except for alkalinity M, sulfite, Mn, temperature and pH. From ANOVA result, it was noted that there was a significant mean difference between the stations except for chromium, manganese and lead. The result showed that the wetland plays a great role in the removal of pollutants where the best performance was obtained at removal efficiency of 96.188% PO4HR,75.63% Nitrate,>99% Cl2, ammonia and nitrite 99.99%, 92.77% sulfate,84.36% Total hardness,87.43% color, and for others it is ranged between 30 and 60%. CONCLUSION: the study concluded that GMF wetland was almost effective and had potential in treatment of the wastewater from the discharging facilities (especially for nutrients, alkalinity P, hardness, color and chloride). It is recommended that wetlands should be conserved and used as wastewater treatment facility.

Thymic MALT lymphoma associated with Sjögren's syndrome with postoperative cardiac tamponade and acute pleuritis: a case report.

BACKGROUND: Thymic mucosa-associated lymphoid tissue (MALT) lymphoma is rare and is known to be associated with Sjögren's syndrome (SjS). SjS is rarely accompanied by serositis. Here, we describe the first case of postoperative cardiac tamponade and acute pleuritis in a patient with thymic MALT lymphoma associated with SjS. CASE PRESENTATION: A 33-year-old woman with SjS presented with an anterior mediastinal mass on chest computed tomography, which was performed for further examination of the condition. Suspecting a thymic MALT lymphoma or thymic epithelial tumor, total thymectomy was performed. The mediastinal mass was histopathologically diagnosed as a thymic MALT lymphoma. The patient was discharged with a good postoperative course but visited the hospital 30 days after surgery for dyspnea. Cardiac tamponade was observed and drainage was performed. Four days after pericardial drainage, chest radiography revealed massive left pleural effusion, and thoracic drainage was performed. The patient was diagnosed with serositis associated with SjS and treated with methylprednisolone, which relieved cardiac tamponade and pleuritis. CONCLUSIONS: Surgical invasion of thymic MALT lymphomas associated with SjS may cause serositis. Postoperative follow-up should be conducted, considering the possibility of cardiac tamponade or acute pleuritis due to serositis as postoperative complications.