B-cell Lymphocytes Research Articles

Mapping integral cell-type-specific interferon-induced gene regulatory networks (GRNs) involved in systemic lupus erythematosus using systems and computational analysis.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder characterized by the production of autoantibodies, resulting in inflammation and organ damage. Although extensive research has been conducted on SLE pathogenesis, a comprehensive understanding of its molecular landscape in different cell types has not been achieved. This study uncovers the molecular mechanisms of the disease by thoroughly examining gene regulatory networks within neutrophils, dendritic cells, T cells, and B cells. Firstly, we identified genes and ncRNAs with differential expression in SLE patients compared to controls for different cell types. Furthermore, the derived differentially expressed genes were curated based on immune functions using functional enrichment analysis to create a protein-protein interaction network. Topological network analysis of the formed genes revealed key hub genes associated with each of the cell types. To understand the regulatory mechanism through which these hub genes function in the diseased state, their associations with transcription factors, and non-coding RNAs in different immune cell types were investigated through correlation analysis and regression models. Finally, by integrating these findings, distinct gene regulatory networks were constructed, which provide a novel perspective on the molecular, cellular, and immunological landscapes of SLE. Importantly, we reveal the crucial role of IRF3, IRF7, and STAT1 in neutrophils, dendritic cells, and T cells, where their aberrant upregulation in disease states might enhance the production of type I IFN. Furthermore, we found MYB to be a crucial regulator that might activate T cells toward autoimmune responses in SLE. Similarly, in B-cell lymphocytes, we found FOXO1 to be a key player in autophagy and chemokine regulation. These findings were also validated using single-cell RNASeq analysis using an independent dataset. Genotype variations of these genes were also explored using the GWAS central database to ensure their targetability. These findings indicate that IRF3, IRF7, STAT1, MYB, and FOXO1 are promising targets for therapeutic interventions for SLE.

Pathological and Immunohistochemical Characterization of Follicular Gastritis (Gastric Lymphofollicular Hyperplasia) in 41 Dogs.

Gastric lymphofollicular hyperplasia (GLFH) is characterized by large lymphoid nodules in the lamina propria. Its etiology and immunohistochemical characteristics are poorly understood. This study analyzed 41 canine GLFH cases, including clinical, endoscopic, histopathological, and immunohistochemical evaluations. Young French Bulldogs (75.06%) were the most affected. Endoscopically, lymphoid nodules were identified in both the antrum and gastric body. Lymphoid follicle diameters were similar in the gastric body (mean 295.587 μm) and antrum (mean 294.641 μm). Associated lesions included glandular atrophy, lymphoplasmacytic inflammation, and fibrosis. Minimal, moderate, and severe colonization with Helicobacter-like organisms (HLOs) were observed in 20, 6, and 3 cases, respectively. B-cell lymphocytes positive for Bcl6 and Pax5 were localized centrally in large follicles, surrounded by CD3+ T lymphocytes. Small follicles lacked germinal centers and showed mixed T and B lymphocytes. A positive correlation was found between the follicle diameter and both HLOs colonization (p = 0.049) and follicular hyperplasia (p < 0.001). A regression analysis indicated that HLOs colonization and hyperplasia accounted for 42.3% of follicle diameter variance (R2 = 0.423, p < 0.001). Additional studies are required to investigate potential correlations between GLFH and HLOs, as well as to assess the role of this lesion in the progression to neoplasia.

Hepatic methotrexate-associated lymphoproliferative disease: a case report and literature review

BackgroundMethotrexate-associated lymphoproliferative disease (MTX–LPD) is a rare and life-threatening complication of MTX administration. MTX–LPD features more extranodal lesions than malignant lymphoma; however, the liver is an extremely rare organ that develops LPD. Herein, we present a case of hepatic MTX–LPD treated with surgical resection. We also reviewed the literature on hepatic MTX–LPD.Case presentationA 66-year-old man with a history of rheumatoid arthritis (RA) was admitted to our department for the treatment of hepatic solitary liver tumor. The patient had been receiving MTX (14 mg/week) for RA for 6 years. MTX was withdrawn and salazosulfapyridine was prescribed 3 weeks prior to admission because of mediastinal MTX–LPD. Abdominal contrast-enhanced computed tomography showed a slightly ring-like enhanced hypovascularized mass (80 mm) in the lateral section of the liver. Carbohydrate antigen 19-9 (78.1 U/mL) level was elevated. No evidence was observed on esophagogastroduodenoscopy or colonoscopy. The tumor was suspected to be an intrahepatic cholangiocarcinoma. The patient underwent hepatic lateral sectionectomy and lymphadenectomy. Pathological examination revealed that the hepatic mass was coagulative necrosis of the CD20-positive B-cell lymphocytes. These histological findings were similar to those of rapid necrotic lymphoma. MTX–LPD is known to spontaneously regress after withdrawing MTX, and the patient was diagnosed with hepatic MTX–LPD.ConclusionsMTX–LPD can occur in the liver. Clinician should suspect hepatic MTX–LPD when a liver mass is detected in patient who had been treating with MTX for RA.

The effect of leflunomide on B-cell lymphocytes in vitiligo

The effect of leflunomide on B-cell lymphocytes in vitiligo

B Cell Lymphocytes as a Potential Source of Breast Carcinoma Marker Candidates.

Despite advances in the genomic classification of breast cancer, current clinical tests and treatment decisions are commonly based on protein-level information. Nowadays breast cancer clinical treatment selection is based on the immunohistochemical (IHC) determination of four protein biomarkers: Estrogen Receptor 1 (ESR1), Progesterone Receptor (PGR), Human Epidermal Growth Factor Receptor 2 (HER2), and proliferation marker Ki-67. The prognostic correlation of tumor-infiltrating T cells has been widely studied in breast cancer, but tumor-infiltrating B cells have not received so much attention. We aimed to find a correlation between immunohistochemical results and a proteomic approach in measuring the expression of proteins isolated from B-cell lymphocytes in peripheral blood samples. Shotgun proteomic analysis was chosen for its key advantage over other proteomic methods, which is its comprehensive and untargeted approach to analyzing proteins. This approach facilitates better characterization of disease-associated changes at the protein level. We identified 18 proteins in B cell lymphocytes with a significant fold change of more than 2, which have promising potential to serve as breast cancer biomarkers in the future.

Polyserositis as an Initial Manifestation of Chronic Lymphocytic Lymphoma

Abstract Chronic lymphocytic lymphoma (CLL) is a lymphoproliferative malignancy characterized by the generation and accumulation of CD5+ monoclonal B-cell lymphocytes, which are physically mature lymphocytes with aberrant immunological activity. The common presenting features are lymphadenopathy and leukocytosis. Because of its asymptomatic and indolent appearance, CLL requires a high index of suspicion to be diagnosed. Our patient presented with unusual symptoms of malignant polyserositis without substantial lymphadenopathy or hepatosplenomegaly. Ascitic fluid cytology and flow cytometry were done to confirm the diagnosis. The patient was staged modified Rai 0 and Binet A and categorized as low-risk status. Treatment is usually advised at Rai stage II and Binet stage B and higher. Although there is no mention of ascites or pleural effusion in the staging disease or deciding therapy, malignant polyserositis carries a poor prognosis and the decision to treat should be individualized. Our patient was offered chemotherapy but the patient denied it. He was on regular follow-ups receiving palliative therapy.

A comprehensive exploration of diverse skin cell types in the limb of the desert tortoise (Testudo graeca) through light, transmission, scanning electron microscopy, and immunofluorescence techniques

The Greek tortoise, inhabiting harsh desert environments, provides a compelling case for investigating skin adaptations to extreme conditions. We have utilized light microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and immunofluorescence analysis to describe the structure of the arid-adapted limb skin in the Greek tortoise. Our aim was to identify the cell types that reflect the skin adaptation of this tortoise to arid conditions. Utilizing seven antibodies, we localized and elucidated the functions of various skin cells, shedding light on how the tortoise adapts to adverse environmental conditions. Our findings unveiled numerous scales on the limbs, varying in size and color, acting as protective armor against abrasions, bites, and other potential threats in their rocky habitats. The epidermis comprises four layers: stratum basalis, stratum spinosum, peri-corneous layer, and stratum corneum. Cytokeratin 14 (CK14) was explicitly detected in the basal layer of the epidermis, suggesting a role in maintaining epidermal integrity and cellular function. Langerhans cells were observed between epidermal cells filled with ribosomes and Birbeck granules. Numerous dendritic-shaped Langerhans cells revealed through E-Cadherin signify strong immunity in tortoises' skin. Melanophores were identified using the Melan-A antibody, labeling the cytoplasm, and the SOX10 antibody, labeling the nucleus, providing comprehensive insights into melanophores morphology and distribution. Two types of melanophores were found: dendritic below the stratum basalis of the epidermis and clustered oval melanophores in the deep dermal layer. Varied melanophores distribution resulted in a spotted skin pattern, potentially offering adaptive camouflage and protection against environmental challenges. Numerous myofibroblasts were discerned through alpha-smooth actin (α-SMA) expression, indicating that the Greek tortoise's skin possesses a robust tissue repair and remodeling capacity. B-cell lymphocytes detected via CD20 immunostaining exhibited sporadic distribution in the dermis, concentrating in lymphoid aggregates and around vessels, implying potential roles in local immune responses and inflammation modulation. Employing Tom20 to identify skin cells with abundant mitochondria revealed a notable presence in melanophores and the basal layer of the epidermis, suggesting high metabolic activity in these cell types and potentially influencing cellular functions. These findings contribute to our comprehension of tortoise skin anatomy and physiology, offering insights into the remarkable adaptations of this species finely tuned to their specific environmental habitats.

Peritoneal lymphomatosis with pleural and peritoneal effusions in a dog: a case report

Peritoneal lymphomatosis (PL) is a rare lymphoid neoplasm in dogs. A nine-year-old spayed female Labrador retriever presented with pleural and peritoneal effusions. Diagnostic imaging revealed diffuse nodular to massive lesions in the mesentery, particularly in the caudal abdomen. While the superficial lymph nodes did not show significant changes, enlargement was observed in the intra-abdominal and intra-thoracic lymph nodes. Cytological and flow cytometric analyses of the effusion indicated the presence of large B-cell lymphocytes expressing CD3-/CD5-/CD14-/CD21-/CD34+/CD45+/CD79a+. PL was diagnosed using diagnostic imaging and fluid analysis. This case report highlights the clinical and diagnostic features of canine PL.

Hematological manifestations of Helicobacter Pylori (literature review)

It is known that Helicobacter pylori to be a key factor in the etiology of various gastrointestinal diseases, ranging from chronic gastritis without clinical symptoms to peptic ulcer, autoimmune gastritis, adenocarcinoma and gastric MALT lymphoma. However, current research suggests that Helicobacter pylori may be associated with numerous extra-gastric diseases that lead to chronic local or systemic inflammation and the initiation of autoimmune reactions, including hematological ones. The article describes the role of Helicobacter pylori CagA in the pathogenesis of iron deficiency anemia, immune thrombocytopenic purpura and MALT lymphoma. Studies of the iron-deficiency anemia pathogenesis in infected H. pylori patients have shown a connection between the CagA oncoprotein and iron homeostasis. It was established that transferrin endocytosis is mediated and iron absorption increases. In the development of immune thrombocytopenic purpura, CagA leads to a systemic host immune response through mechanisms of molecular mimicry. In pathogenesis of MALT lymphoma, it is considered significant that after the transfer of CagA to B-cell lymphocytes, through the type 4 secretory system (T4SS), a phosphorylated CagA-SHP2 complex is formed by affecting endoplasmic reticulum kinases 1 and 2 (ERK1, ERK2), p38MAPK, BCL2 and NF -κB, as well as through inhibition of p53 accumulation or inhibition of the JAK-STAT signaling pathway, ultimately promoting lymphogenesis and immortalization of B-cell lymphocytes. So, it was established that the presence of CagA protein in the Helicobacter pylori strain is key to the development of inflammation and tumor transformation. The disclosure of these mechanisms is necessary for a more accurate understanding of some pathological processes caused by this bacterium, both in the stomach and outside it. This will help improve diagnosis, guide treatment and predict clinical prognosis. Keywords: hypomagnesaemia, blood pressure, diabetes mellitus.

Decrease in naturally occurring antibodies against epitopes of Alzheimer’s disease (AD) risk gene products is associated with cognitive decline in AD

BackgroundNaturally occurring antibodies (NAbs) are germline-encoded immunoglobulins that can bind to and clear out self-neo-epitopes as well as apoptotic and necrotic cells. However, NAbs pathological relevance in Alzheimer’s disease (AD) is not well-understood.MethodsTwenty-eight candidate proteins encoded by AD-associated genes were selected for this study based on a number of selection criteria, including preferential expression in the brain and B-lymphocyte cells. The levels of NAbs in plasma were analyzed according to their epitopes in age- and gender-matched cognitively normal subjects (CN, n = 56), subjects with mild cognitive impairment (MCI, n = 16) and subjects with AD (n = 56). We aimed to study the levels of their NAbs in plasma and their associations with cognitive decline in individuals with AD.ResultsOf the 28 antigens tested, 17 showed decreased NAbs in individuals with AD; in particular, NAb-TREM2 had an area under the ROC curve of 0.806, with the highest sensitivity (0.370) at 95% specificity among all 28 tests. Further protein–protein interaction networks and functional enrichment analysis suggested that target genes were enriched in AD-related pathological processes classified under “Alzheimer’s disease”, “neurodegenerative disease” and “amyloidosis”. The “Alzheimer’s disease” and “neurodegenerative disease” clusters, which converged on the initial “recognition” step of microglial phagocytosis, showed the best diagnostic performance for AD.ConclusionsThis study suggests a decline in the function of the adaptive immune system in AD, and the levels of circulating NAbs are likely to serve as biomarkers for surveilling the progression of AD.

Computational predictions of 3D chromatin many-body interactions reveal roles of chromatin hubs in gene expression.

Chromatin 3D organization plays important roles in the regulation of gene expression. Hi-C measurements provide a projection of 3D chromatin organization onto a 2D heatmap, which depicts the population-averaged pairwise contact frequencies between all genomic elements. These 2D heatmaps highlight structural units of chromatin organization such as TADs. As distal cis-regulatory elements such as enhancers interact with promoters to increase the transcriptional output of target genes in a tissue-specific manner, quantifying cell-type specific chromatin spatial organization is therefore critical. However, TADs have been found to be largely invariant across cell types, suggesting that features of 2D Hi-C heatmaps are insufficient to gain understanding of tissue-specific gene expression. Another challenge is when multiple genomic elements are involved: It is not possible to obtain higher-order many-body interactions from Hi-C data. In order to address these problems, we apply CHROMATIX, a computational method which reconstructs ensembles of single-cell chromatin conformations by deconvolving Hi-C data. We reconstructed large ensembles (2×104) of independent 3D single-cell chromatin conformations which reproduce imaging, Dip-C, and 3D FISH single cell measurements. The reconstructed ensembles of single-cell chromatin structures further enable us to uncover statistically significant 3D hubs of higher-order many-body interactions. We uncovered chromatin hubs of many-bodies across hundreds of loci in B-lymphocyte cells. We illustrate the functional roles of these 3D hubs of many-body interactions in regulating gene expression. Using the example of eQTL associated genes, we show that higher-order 3D hubs provide the physical basis of differential gene expression, with detailed examples of hubs of 1-gene-to-many-eQTLs and many-genes-to-1-eQTL. Overall, our results show 3D chromatin many-body hubs are important for regulating gene expression, and they can be discovered through CHROMATIX computational modeling single-cell 3D chromatin conformations using population Hi-C data.

Case Report of a 60-Year-Old Woman with Autoimmune Hemolytic Anaemia after Venetoclax

Background: Chronic Lymphocytic Leukaemia (CLL) is a common haematological malignant neoplasm that is characterized by proliferation of clonal B-cell lymphocytes and infiltration of blood, lymph nodes, spleen and bone marrow. Autoimmune Hemolytic Anaemia (AIHA) is a medical condition in which patient’s red blood cells are being destructed by immune system through antibodies leading to red blood cell lysis. Venetoclax is a novel BCL-2 selective inhibitor introduced amongst patients with CLL refractory to standard treatment lines. Common adverse events in Venetoclax treatment are: neutropenia, thrombocytopenia and diarrhea. Case Report: The following case study presents 60-year-old female patient that developed an autoimmune hemolytic anemia after introducing Venetoclax for CLL diagnosed nearly 13 years before and treated with many other treatment lines. AIHA was resolved after withdrawing Venetoclax and being treated with steroids, Rituximab and plasmapheresis. After that, Venetoclax was reintroduced with carefully monitored hemolysis markers as well as maintaining steroids and Rituximab treatment with good results. Conclusion: Although AIHA caused by Venetoclax is still not mentioned by producer’s summary of product characteristic (sPC), it is valuable for clinicians to have the knowledge that such adverse event may occur (diagnosed after eliminating other causes) and how it can be handled based on experiences of fellow clinicians.

Unusual Association of Non-paraneoplastic Variant of Lambert-Eaton Myasthenic Syndrome with Predominant B-cell Inflammatory Myopathy

Introduction: Myasthenia gravis disease (MGD) and inflammatory myopathy (IM) are commonly reported in the literature and usually appear with thymic pathology. Lambert-Eton myasthenic syndrome (LEMS) associated with IM is extremely rare. Case Presentation: We report a 42-year-old female patient who presented with proximal muscle weakness of the upper and lower limbs, normal creatinine kinase (CK) level, and positive acetylcholine and voltage-gated calcium channel receptor antibodies. There were no oculobulbar symptoms and no history of thymoma, and the electrophysiological tests were unremarkable. Muscle biopsy revealed focal perimysial and perivascular inflammation, predominantly B-cell lymphocytes, in a non-necrotizing muscle. Conclusions: LEMS associated with IM, particularly B-cell inflammation, has never been reported in the absence of cancer history. Clinical investigations and myopathological features can help establish the diagnosis.

Flow Cytometry Analysis Reveals a Wide Cytologic and Immunophenotypic Spectrum of Peripheral B Lymphocytes in Angioimmunoblastic T-Cell Lymphoma

Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive T-cell lymphoma commonly associated with B-cell dysregulation. Correlations involving B-cell dysregulation and clinicopathological features remain unclear. Methods: We prospectively collected blood samples from 11 AITL patients and 17 healthy controls. The percentages of B-cell subpopulations and lymphocytes with IL-21 production were assessed using flow cytometry. Peripheral blood lymphocyte morphology was evaluated microscopically. Results: Six of 11 (54.5%) patients presented with polyclonal hypergammaglobulinemia. Three of 11 (27.3%) tumor biopsies showed monoclonal immunoglobulin gene rearrangement. The patients exhibited significantly lower levels of naive (p < 0.001) and class-switched (p < 0.001) B cells than controls. The percentages of IgD−CD27− B cells (p = 0.007) and antibody-secreting cells (ASCs) (p = 0.001) were increased. Blood smears revealed atypical lymphocytes and immature plasma cells with morphological diversity. In comparison to normal controls, IL-21 production significantly increased in CD4+ (p < 0.001) and CD8+ (p = 0.020) T cells. B-cell clonality, RHOA G17V mutation, and the presence of sheets of clear cells and immature/mature plasma cells in lymph nodes were significantly associated with percentages of class-switched B cells and ASCs. The patients with circulating EBV DNA had a lower percentage of naive B cells (p = 0.009). Conclusions: Our results demonstrated a wide spectrum of peripheral B-cell morphologies and immunophenotypes of peripheral B cells in AITL. These findings correspond to dysregulated B-cell immunity and heterogeneous clinicopathological features.

HDAC inhibitor Vorinostat and BET inhibitor Plx51107 epigenetic agents' combined treatments exert a therapeutic approach upon acute myeloid leukemia cell model.

The process of cancer initiation and development is regulated via the transcriptional expression of cells going under genomic and epigenetic changes. Targeting epigenetic "readers", i.e., bromodomains (BRD) and post-translational modifications of nucleosomal histone proteins regulate gene expression in both cancerous and healthy cells. In this study, the new epigenetic agent BRD inhibitor PLX51107 and histone deacetylase (HDAC) inhibitor SAHA' s (Vorinostat) single/combined applications' reflections were analyzed in case of cell proliferation, cytotoxicity, apoptosis, cell cycle arrest, and finally target gene expression regulation upon both AML and healthy B-lymphocyte cells; HL60 and NCIBL2171, respectively; in vitro. Since mono treatments of either Vorinostat or Plx51107 regulated cellular responses such as growth, proliferation, apoptosis, and cell cycle arrest of tumor cells; their combination treatments exerted accelerated results. We detected that combined treatment of Plx51107 and Vorinostat strengthened effects detected upon leukemic cells for gaining more sensitization to the agents, decreasing cell proliferation, dramatically inducing apoptosis, and cell cycle arrest; thus regulating target gene expressions. We have shown for the first time that the newly analyzed BRD inhibitor Plx51107 could be a promising therapeutic approach for hematological malignancies and its mono or combined usage might support a rapid transition to clinical trials.

Integrated analysis of long-noncoding RNA and circular RNA expression in Peste-des-Petits-Ruminants Virus (PPRV) infected marmoset B lymphocyte (B95a) cells.

Peste-des-Petits-Ruminants (PPR) or goat plague is an important viral disease of sheep and goats caused by the small ruminant morbilli virus or PPR virus (PPRV). Long non coding RNAs (lncRNA) and circular RNAs (circRNA) play a pivotal role in several biological processes including regulation of virus-host interactions. The present study explored the expression of lncRNA, circRNA and their functions in PPRV infected B-lymphocyte (B95a) cells. The results revealed a total of 4531 lncRNA and 2348 circRNA expression in both mock and PPRV infected samples. Analysis of differentially expressed (DE) RNA identified 123 DE-lncRNA and 39 DE-circRNA as significantly dysregulated. Functional analysis of cis-target genes of DE-lncRNA indicated activation of TCF dependent WNT signaling and PKN1 stimulated transcription process. Interactions (sponging) of microRNA (miRNA) revealed 344 DE-lncRNA-miRNA and 93 DE-circRNA-miRNA pairs. The competing endogenous RNA (ceRNA) network of lncRNA/circRNA-miRNA-mRNA in PPRV infected B95a cells was represented by 69 ceRNA pairs. We validated the DE-circRNA by targeted amplification and sequencing of back spliced junctions (BSJs). The present study revealed a profile of lncRNA, circRNA and their potential ceRNA network in PPRV infection. The results provide insight for better understanding of PPRV-host interactions.

Destructive inflammatory reaction after an autologous retinal pigment epithelium and choroid transplantation: no detection of an auto-immune response

PurposeFive patients who underwent uncomplicated retinal pigment epithelium (RPE)-choroid transplantation for neovascular age-related macular degeneration developed a destructive inflammatory reaction causing subretinal fluid accumulation and extensive RPE atrophy in the graft. We hypothesized that this inflammation could be caused by an auto-immune response against the graft, resulting in circulating auto-antibodies. The aim of our study was to examine a potential autoimmune origin, which would allow a more targeted therapy approach.MethodsFive above-mentioned patients and four control groups of five patients each were included: 1) after uncomplicated RPE-choroid transplantation, 2) after full macular translocation, 3) treated with anti-vascular endothelial growth factor, and 4) healthy controls. Histopathology of rejected graft tissue was performed using standard procedures. Presence of RPE-choroid autoantibodies in serum was examined by indirect immunofluorescence and Western blot, and human leukocyte antigen (HLA) typing was performed.ResultsHistopathological examination of an explanted graft showed infiltration of T-lymphocytes and macrophages in the choroid and RPE, and an increased number of B-cell lymphocytes were found in the choroid. Indirect immunofluorescence showed weak RPE-choroid autoantibody immunoreactivity in three patients of different groups. Western blot did not show specific RPE-choroid autoantibody immunoreactivity and no difference of HLA genotypes between the groups was found.ConclusionsAlthough local mononuclear inflammatory cell infiltration and a high number of B-lymphocytes were observed in an explanted graft, we did not detect serological evidence of an autoimmune origin of the postoperative inflammation using direct immunofluorescence and Western Blot. Alternatively, the graft failure may have been caused by local innate inflammation, triggered by breakdown of tolerance. Based on our current findings of this small study group, we have no rationale to pursue therapies targeted towards autoreactive graft failure. More research is needed to confirm our findings.

Presentation of multiple myeloma with absolute lymphocytosis? Coexistence of CLL &amp; multiple myeloma

The presence of a chronic lymphocytic leukemia and multiple myeloma in a single patient is very rare. Multiple myeloma is a plasma cell disorder, whereas CLL (Chronic Lymphocytic Leukemia) is the mature B-cell lymphocytes disorder. We described a 50 year-old man who presented with fatigue and lethargy of 1 month duration. He was found to be anemic, with lymphocytosis, decreased renal function, high calcium level, and conspicuous M-Spike on serum electrophoresis. Furthermore, peripheral smear &amp; bone marrow biopsy demonstrated two distinct hematological malignancies on morphological basis.

Inflammatory Pseudotumor Simulating a Jugular Foramen Meningioma: Case Report, Technical Video, and Literature Review

Inflammatory pseudotumor (IP) is a nonneoplastic, reactive inflammatory process, of unknown etiology, characterized by a proliferation of connective tissue with an inflammatory infiltrate, most commonly involving the lungs and orbits. Primary intracranial IP is an extremely rare entity often arising from the meningeal structures of the skull base. We reported an extremely rare case of a primary intracranial IP located in the cerebellopontine angle, mimicking a jugular foramen meningioma. We further illustrated our microsurgical technique through a surgical video and performed a review of the pertinent scientific literature. The patient underwent gross total microsurgical resection of the tumor mass through a left retrosigmoid approach. Intraoperative neuromonitoring of the VII-VIII cranial nerve complex and lower cranial nerve was performed, and thulium laser fibers were used as a tool for tumor debulking. Postoperatively, the patient's neurologic symptoms recovered. Histopathologic studies showed dense infiltrate of T- and B-cell lymphocytes and epithelioid granulomas, compatible with the diagnosis of IP. Postoperatively, magnetic resonance imaging scans showed complete tumor resection. The patient underwent a 3-month oral corticosteroid therapy showing no signs of recurrence at the radiologic follow-up. Primary intracranial IPs are rare pathologic entities that can mimic extraaxial tumors and should be taken into consideration as a potential differential diagnosis. Complete microsurgical resection in combination with other treatments (steroids therapy, radiotherapy) is the most common treatment of choice and is associated with good outcomes and low rates of recurrence.

The molecular and cellular mechanisms associated with the destruction of terminal bronchioles in COPD.

Peripheral airway obstruction is a key feature of chronic obstructive pulmonary disease (COPD), but the mechanisms of airway loss are unknown. This study aims to identify the molecular and cellular mechanisms associated with peripheral airway obstruction in COPD. Ten explanted lung specimens donated by patients with very severe COPD treated by lung transplantation and five unused donor control lungs were sampled using systematic uniform random sampling (SURS), resulting in 240 samples. These samples were further examined by micro-computed tomography (CT), quantitative histology and gene expression profiling. Micro-CT analysis showed that the loss of terminal bronchioles in COPD occurs in regions of microscopic emphysematous destruction with an average airspace size of ≥500 and <1000 µm, which we have termed a "hot spot". Based on microarray gene expression profiling, the hot spot was associated with an 11-gene signature, with upregulation of pro-inflammatory genes and downregulation of inhibitory immune checkpoint genes, indicating immune response activation. Results from both quantitative histology and the bioinformatics computational tool CIBERSORT, which predicts the percentage of immune cells in tissues from transcriptomic data, showed that the hot spot regions were associated with increased infiltration of CD4 and CD8 T-cell and B-cell lymphocytes. The reduction in terminal bronchioles observed in lungs from patients with COPD occurs in a hot spot of microscopic emphysema, where there is upregulation of IFNG signalling, co-stimulatory immune checkpoint genes and genes related to the inflammasome pathway, and increased infiltration of immune cells. These could be potential targets for therapeutic interventions in COPD.