Polymorphous Infiltrate Research Articles

Pediatric eosinophilic fasciitis: similarities and differences with adult forms.

The purpose of this study was to identify pediatric eosinophilic fasciitis, which is an extremely rare condition, in order to describe their clinical, paraclinical, and therapeutic characteristics. We made a call for observations via societies for pediatric rheumatology in France and surrounding countries and collected clinical and paraclinical data of the cases fulfilling the diagnostic criteria. Eight patients under 18years of age with confirmed eosinophilic fasciitis followed between April 2004 and July 2022 in France, Germany, Italy, and Spain were included. The median age of onset of symptoms was 8.7years (range 3 to 12.6). All patients had skin and joint involvement at diagnosis. Eosinophilia was present at diagnosis in 5/8 patients and 5/7 patients presented hypergammaglobulinemia. All the patients had an MRI, and in 6, we observed thickened fascia with a T2 hypersignal. Five patients had undergone a full-thickness biopsy showing a polymorphic lymphoplasmacytic infiltrate of the fascia in all and the presence of eosinophils in 4 of them. All the patients were treated with corticosteroids with variable regimens and all received at least an immunosuppressant. Conclusion: To our knowledge, this is the largest pediatric series of eosinophilic fasciitis. The clinical and paraclinical presentation seems similar to that of adults except for a form that appears to be distinguished with isolated joint contractures, and hypergammaglobulinemia which appears to be more frequent in children. Dermatological and pathological expertise and MRI are key elements of the diagnosis. The most consensual treatment includes physiotherapy, prolonged corticosteroid therapy, and methotrexate as first-line therapy. What is Known •Eosinophilic fasciitis is a rare condition, especially in children with approximately 60 reportedpediatric cases. •Some pediatric specificities tend to emerge from somereports. What is New •Possible isolated joints contractures andmore frequent hypergammaglobulinemia seem to characterize pediatric eosinophilic fasciitis incomparison with adult forms. •The most frequently used first-line therapy combinesphysiotherapy, corticosteroids and methrotrexate.

MORPHOLOGICAL FEATURES OF THE MUSCULUS MASSETER IN PATIENTS WITH POST-IMMOBILIZATION EXTRA-ARTICULAR CONTRACTURES OF THE MANDIBLE

Aim. To determine the morphological features of the musculus masseter in patients with extra-articular post-immobilization contractures of the mandible. Materials and methods. The research material was fragments of the musculus masseter, which were divided into three groups. Group 1 included musculus masseter fragments from 8 people, whose autopsy did not reveal any pathology of the head and neck. Group 2 included fragments of the macroscopically altered musculus masseter from 6 people who underwent immobilization of the lower jaw using a double-jaw splinting during the first hospitalization, and metal-osteosynthesis during the second hospitalization. Group 3 included fragments of the macroscopically altered musculus masseter from 6 people who underwent immobilization of the lower jaw using a parieto-chin sling bandage during the first hospitalization, and metal-osteosynthesis during the second hospitalization. In patients of groups 2 and 3, an average of 37.6 days passed between the use of conservative immobilization methods and metal-osteosynthesis. Microslides stained with hematoxylin and eosin, picrofuchsin according to van Gieson were subjected to morphometric examination. Results. In patients with post-immobilization extra-articular contractures of the mandible, changes in the morphofunctional state of the parenchymal and stromal components of the musculus masseter were recorded. In the parenchymal component, wave-like deformation, ischemic-dystrophic and atrophic changes in muscle fibers were noted. The stromal component was characterized by the presence of focal-diffuse polymorphic cellular infiltration; excessive content of connective tissue fibers with the presence of adipocytes between them; a decrease in the number of vessels with the presence of dystrophic-necrotic and desquamative changes in endothelial cells, sclerotic changes in all layers of the vascular wall; dystrophic-sclerotic changes in nerve fibers. Conclusions. The structural changes in the musculus masseter identified by the authors, which are more pronounced in cases of using a parieto-chin sling bandage and less pronounced in cases of using a double-jaw splinting, may underlie the development of post-immobilization extra-articular contractures of the mandible.

Interdigitating dendritic cell sarcoma presenting as retroperitoneal mass and obstructive jaundice. An uncommon entity of complex diagnosis.

A 60-year-old male was admitted for obstructive jaundice secondary to a 2 cm retroperitoneal lesion. Ultrasound endoscopy (UES) with fine needle biopsy (FNB) was performed, as well as endoscopic retrograde cholangiopancreatography (ERCP) with placement of a metal stent for bile duct drainage. Initially IgG4-related disease was suspected from FNB. After 8 months of treatment the patient attended with a progression evidenced in computed tomography (CT) with retroperitoneal adenopathies and liver metastasis, with involvement of duodenum and fistulation towards hepatic angle of colon. Upper endoscopy and colonoscopy was performed. The patient underwent a cephalic duodenopancreatectomy with antrectomy and right hemicolectomy. The histological study of the specimen revealed cells of fascicular distribution, fusiform aspect, with ovoid nuclei, accompanied by a polymorphic inflammatory infiltrate with mononuclear cells. Immunohistochemistry (IHQ) was positive for S100, CD21, CD23, D2-40 and Bcl-2 and negative for CD1a, CD2, CD3, CD4, CD5, CD8, CD20, CD79a, PD1, desmine, langherin, c-kit, PDGFR. These findings were suggestive of interdigitating dendritic cell sarcoma (IDCS). Systemic chemotherapy with R-CHOP was initiated and after the first 4 cycles of treatment, retroperitoneal adenopathies regressed, with stability of metastatic liver disease.

Epstein Barr Virus Positive Mucocutaneous Ulcer versus Classic Hodgkin Lymphoma: Challenges in Diagnosis

Abstract Introduction/Objective Epstein- Barr virus positive mucocutaneous ulcer (EBVMCU) is a clinicopathologic entity first identified in 2010. It occurs in patients with immunosuppression and presents as a well circumscribed ulceration on the oropharyngeal mucosa, skin or gastrointestinal tract. Infiltrates of atypical lymphoid cells that may have appearances similar to Diffuse Large B-cell Lymphoma (DLBCL) or Classic Hodgkin Lymphoma (CHL) are seen. Methods/Case Report A 41 year old male patient with history of HIV infection presented with hematochezia and rectal pain, underwent sigmoidoscopy and a large ulcerated mass was present at the anal verge. Polymorphic infiltrates of small lymphoid cells, eosinophils, granulocytes, plasma cells, histiocytes and scattered large atypical lymphoid cells, morphologically mimicking Reed-Sternberg cells were identified. The large atypical lymphoid cells were positive for CD30, MUM-1, BCL-6, EBER (EBV) and negative for CD3, CD15, CD20, CD45, CD79a, SOX-10. Based on lack of B-symptoms, no lymphadenopathy, superficial lesions, reduced CD4/CD8 ratio and specific location, EBVMCU was favored. Eight months later, he presented with night sweats, decreased appetite and inguinal lymphadenopathy. Lymph node excision displayed infiltrates of predominantly small lymphocytes, histiocytes, plasma cells and eosinophils. Foci of scattered large atypical cells morphologically compatible with Hodgkin/Reed Sternberg cells with focal necrosis were noted. The atypical cells were positive for CD30, PAX5 (weak), CD20 (subset), CD15 (focal), MUM-1 and EBV-EBER. CHL, Mixed Cellularity Subtype was diagnosed. Results (if a Case Study enter NA) NA Conclusion As a newer entity, we don’t know if EBVMCU can co-exist with or progress to CHL/DLBCL. Therefore, EBVMCU patients should undergo vigilant screening.

Integrated machine learning and Mendelian randomization reveal PALMD as a prognostic biomarker for nonspecific orbital inflammation

Background: Nonspecific Orbital Inflammation (NSOI) remains a perplexing enigma among proliferative inflammatory disorders. Its etiology is idiopathic, characterized by distinctive and polymorphous lymphoid infiltration within the orbital region. Preliminary investigations suggest that PALMD localizes within the cytosol, potentially playing a crucial role in cellular processes, including plasma membrane dynamics and myogenic differentiation. The potential of PALMD as a biomarker for NSOI warrants meticulous exploration. Methods: PALMD was identified through the intersection analysis of common DEGs from datasets GSE58331 and GSE105149 from the GEO database, alongside immune-related gene lists from the ImmPort database, using Lasso regression and SVM-RFE analysis. GSEA and GSVA were conducted with gene sets co-expressed with PALMD. To further investigate the correlation between PALMD and immune-related biological processes, the CIBERSORT algorithm and ESTIMATE method were employed to evaluate immune microenvironment characteristics of each sample. The expression levels of PALMD were subsequently validated using GSE105149. Results: Among the 314 DEGs identified, several showed significant differences. Lasso and SVM-RFE algorithms pinpointed 15 hub genes. Functional analysis of PALMD emphasized its involvement in cell-cell adhesion, leukocyte migration, and leukocyte-mediated immunity. Enrichment analysis revealed that gene sets positively correlated with PALMD were enriched in immune-related pathways. Immune infiltration analysis indicated that resting dendritic cells, resting mast cells, activated NK cells, and plasma cells positively associate with PALMD expression. Conversely, naive B cells, activated dendritic cells, M0 and M1 macrophages, activated mast cells, activated CD4 memory T cells, and naive CD4 T cells showed a negative correlation with PALMD expression. PALMD demonstrated significant diagnostic potential in differentiating NSOI. Conclusions: This study identifies PALMD as a potential biomarker linked to NSOI, providing insights into its pathogenesis and offering new avenues for tracking disease progression.

Eosinophilic dermatosis of haematologic malignancy treated with ibrutinib: A case report

AbstractEosinophilic dermatosis of haematologic malignancy is an infrequent skin disorder characterised by severe pruritus and skin lesions resembling arthropod bites. It primarily affects individuals with underlying haematological conditions, most commonly chronic lymphocytic leukaemia (CLL). While it does not correlate with a worse prognosis for the haematological disease itself, it significantly impacts patients' quality of life due to the distressing pruritus and recurring nature. Clinical presentation typically shows erythematous papules resembling arthropod bites, with less frequent occurrences of urticarial plaques or bullous lesions. Histologically, an intense and polymorphous inflammatory infiltrate is found both in the superficial and deep dermis, marked by an abundance of eosinophils and the absence of atypical cells. Treatment of this disease remains uncertain, with corticosteroids often being the only effective therapy. Here, we present the case of an 80‐year‐old patient with a history of CLL, who experienced a widespread, itchy eruption of papules and plaques over 2 months. Despite various therapeutic attempts, the lesions only responded to high‐dose corticosteroids. Following the initiation of ibrutinib at a daily dose of 420 mg, both the skin lesions and pruritus resolved within 3 months. Ibrutinib, a tyrosine kinase inhibitor, is approved as a first‐line treatment for CLL. However, its potential as a remedy for refractory eosinophilic dermatosis has not been reported thus far.

Changes in the liver of Djungarian hamsters under conditions of a three-month supply of water-soluble silicon of various concentrations

BACKGROUND: Silicon enters the human body through drinking water, air and food. Silicon nanoparticles used in the cosmetic, pharmaceutical and food industries are known to have biological activity. Taking into account the widespread prevalence of silicon compounds, the issue of the safety of its use is becoming more urgent. AIM: To study the effect of water-soluble silicon on the morphological structure of the liver of Djungarian hamsters for three months. MATERIALS AND METHODS: The experiment was carried out on Djungarian hamsters kept in normal vivarium conditions under natural light. The animals were divided into three groups: control, which received bottled drinking water; the first experimental group, which received the same water, but with the addition of sodium metasilicate nine-hydrate at a concentration of 10 mg/l in terms of silicon; the second experimental group, which also received the same water, but with the concentration of sodium metasilicate nine-hydrate doubled (up to 20 mg/l). After three months, the animals were removed from the experiment. Sections were processed by general histological (hematoxylin and eosin, Van Gieson method, toluidine blue), histochemical (monoamine oxidase-positive cells) methods. RESULTS: In the liver of hamsters from the experimental groups, changes in the micromorphological structure were revealed, such as an increase in the nuclear area, nuclear-cytoplasmic ratio of hepatocytes, and the diameter of sinusoidal capillaries. Moreover, more pronounced changes were observed in the liver of hamsters of the second experimental group, such as polymorphic cell infiltration of the portal tracts, an increase in the number of eosinophils, deformation of hepatocyte nuclei and the appearance of apoptotic bodies. A decrease in the area of mast cells and an increase in their number, as well as the number of monoamine oxidase-positive cells in the liver of hamsters of both experimental groups were recorded. CONCLUSIONS: An increase in the concentration of silicon supplied with drinking water in both cases is reflected in the micromorphological structure of the liver of hamsters. Moreover these changes are more pronounced in the liver of hamsters of the second experimental group.

Clinicopathological Profile of Pyoderma Gangrenosum: A 10-Year Retrospective Study from a Tertiary Care Center in South India.

Pyoderma gangrenosum (PG) is a reactive neutrophilic inflammatory dermatosis with a varied clinicopathologic presentation. It commonly manifests as rapidly progressive painful ulcers, mimicking varied conditions including infections, vasculitis, and malignancies, and is a diagnosis of exclusion. There are scarce data on PG from the Indian subcontinent. The aim of the study was to study the clinicopathologic profile of patients with PG and their underlying systemic associations. A retrospective observational study was done between 2011 and 2021, and patients diagnosed as PG based on the diagnostic tool proposed by Maverakis et al. were recruited and their demographic, clinical, and histological findings were obtained. Among 54 patients with suspected PG, 17 patients (eight males and nine females) fulfilled the diagnostic criteria, and the mean age of disease onset was 32.1 years (range: 3-60 years). Ulcerative variant was the most common type (9/17, 52.9%), and 29.4% had systemic associations including autoinflammatory syndromes. The onset at atypical sites such as face and hand were noted in one patient each. Histopathology revealed a polymorphous dermal infiltrate with neutrophilic predominance in the majority (94.1%). Systemic steroids (dose ranging from 0.5-1 mg/kg prednisolone equivalent) were used in 11/17 (64.7%) patients. The commonly used alternative drugs included clofazimine (47%), minocycline (29%), thalidomide (23.5%), adalimumab and mycophenolate mofetil in 17.6% each, dapsone and ciclosporine in 11.7% each. Remission was achieved between two weeks and three months in 10 (58.8%) patients after treatment initiation and two mortalities (11.7%) were recorded. PG can affect any age group and may be localized to rarer, atypical sites. The possibility of underlying autoinflammatory conditions should be considered in addition to the evaluation of other disorders like inflammatory bowel disease, hematological disorders, and rheumatological disorders.

Inflammatory Pseudotumor of the Liver or Intrahepatic Cholangiocarcinoma, That's the Question: A Review of the Literature.

An inflammatory pseudotumor of the liver is a rare tumor-like lesion composed of polymorphous inflammatory cell infiltrates and variable amounts of fibrosis that can often mimic a malignant liver neoplasm. The etiology of inflammatory pseudotumors of the liver is unknown; symptoms are faint and imaging non-specific. Thus, it is often hard to make a diagnosis preoperatively and it is not so rare to over-treat patients with this disease or vice versa. Thus, more profound knowledge is necessary to plan appropriate disease management. We reported our two cases and systematically searched the literature regarding IPTL. We selected articles published in English from four databases, PubMed, Scopus, Web of Science and Google Scholar, and we included only articles with consistent data. Twenty nine papers fulfilling criteria for the review were selected. The analysis of 69 cases published from 1953 confirmed that the risk factors are unclear, the imaging data is not specific, and biopsy is crucial but not so widely used in clinical practice due to the procedure's related risks, and relatively low effectiveness and improvement in imaging analysis. Regarding treatment, surgeons have moved towards a more conservative attitude over the years due to better imaging quality and patient surveillance. However, surgery remains the modality of choice for most cases with an indeterminate diagnosis. Even if an inflammatory pseudotumor of the liver is a benign tumor with a good prognosis, not requiring any treatment in most cases, sometimes it remains challenging to differentiate it from ICC; therefore, there is a solid recommendation to manage this condition with a multidisciplinary team.

Deciphering the role of HLF in idiopathic orbital inflammation: integrative analysis via bioinformatics and machine learning techniques

Idiopathic orbital inflammation, formerly known as NSOI (nonspecific orbital inflammation), is characterized as a spectrum disorder distinguished by the polymorphic infiltration of lymphoid tissue, presenting a complex and poorly understood etiology. Recent advancements have shed light on the HLF (Human lactoferrin), proposing its critical involvement in the regulation of hematopoiesis and the maintenance of innate mucosal immunity. This revelation has generated significant interest in exploring HLF's utility as a biomarker for NSOI, despite the existing gaps in our understanding of its biosynthetic pathways and operational mechanisms. Intersecting multi-omic datasets—specifically, common differentially expressed genes between GSE58331 and GSE105149 from the Gene Expression Omnibus and immune-related gene compendiums from the ImmPort database—we employed sophisticated analytical methodologies, including Lasso regression and support vector machine-recursive feature elimination, to identify HLF. Gene set enrichment analysis and gene set variation analysis disclosed significant immune pathway enrichment within gene sets linked to HLF. The intricate relationship between HLF expression and immunological processes was further dissected through the utilization of CIBERSORT and ESTIMATE algorithms, which assess characteristics of the immune microenvironment, highlighting a noteworthy association between increased HLF expression and enhanced immune cell infiltration. The expression levels of HLF were corroborated using data from the GSE58331 dataset, reinforcing the validity of our findings. Analysis of 218 HLF-related differentially expressed genes revealed statistically significant discrepancies. Fifteen hub genes were distilled using LASSO and SVM-RFE algorithms. Biological functions connected with HLF, such as leukocyte migration, ossification, and the negative regulation of immune processes, were illuminated. Immune cell analysis depicted a positive correlation between HLF and various cells, including resting mast cells, activated NK cells, plasma cells, and CD8 T cells. Conversely, a negative association was observed with gamma delta T cells, naive B cells, M0 and M1 macrophages, and activated mast cells. Diagnostic assessments of HLF in distinguishing NSOI showed promising accuracy. Our investigation delineates HLF as intricately associated with NSOI, casting light on novel biomarkers for diagnosis and progression monitoring of this perplexing condition.

The roles of IRF8 in nonspecific orbital inflammation: an integrated analysis by bioinformatics and machine learning

BackgroundNonspecific Orbital Inflammation (NSOI) represents a persistent and idiopathic proliferative inflammatory disorder, characterized by polymorphous lymphoid infiltration within the orbit. The transcription factor Interferon Regulatory Factor 8 (IRF8), integral to the IRF protein family, was initially identified as a pivotal element for the commitment and differentiation of myeloid cell lineage. Serving as a central regulator of innate immune receptor signaling, IRF8 orchestrates a myriad of functions in hematopoietic cell development. However, the intricate mechanisms underlying IRF8 production remain to be elucidated, and its potential role as a biomarker for NSOI is yet to be resolved.MethodsIRF8 was extracted from the intersection analysis of common DEGs of GSE58331 and GSE105149 from the GEO and immune- related gene lists in the ImmPort database using The Lasso regression and SVM-RFE analysis. We performed GSEA and GSVA with gene sets coexpressed with IRF8, and observed that gene sets positively related to IRF8 were enriched in immune-related pathways. To further explore the correlation between IRF8 and immune-related biological process, the CIBERSORT algorithm and ESTIMATE method were employed to evaluate TME characteristics of each sample and confirmed that high IRF8 expression might give rise to high immune cell infiltration. Finally, the GSE58331 was utilized to confirm the levels of expression of IRF8.ResultsAmong the 314 differentially expressed genes (DEGs), some DEGs were found to be significantly different. With LASSO and SVM-RFE algorithms, we obtained 15 hub genes. For biological function analysis in IRF8, leukocyte mediated immunity, leukocyte cell-cell adhesion, negative regulation of immune system process were emphasized. B cells naive, Macrophages M0, Macrophages M1, T cells CD4 memory activated, T cells CD4 memory resting, T cells CD4 naive, and T cells gamma delta were shown to be positively associated with IRF8. While, Mast cells resting, Monocytes, NK cells activated, Plasma cells, T cells CD8, and T cells regulatory (Tregs) were shown to be negatively linked with IRF8. The diagnostic ability of the IRF8 in differentiating NSOI exhibited a good value.ConclusionsThis study discovered IRF8 that are linked to NSOI. IRF8 shed light on potential new biomarkers for NSOI and tracking its progression.

Elucidating the multifaceted roles of GPR146 in non-specific orbital inflammation: a concerted analytical approach through the prisms of bioinformatics and machine learning.

Non-specific Orbital Inflammation (NSOI) is a chronic idiopathic condition marked by extensive polymorphic lymphoid infiltration in the orbital area. The integration of metabolic and immune pathways suggests potential therapeutic roles for C-peptide and G protein-coupled receptor 146 (GPR146) in diabetes and its sequelae. However, the specific mechanisms through which GPR146 modulates immune responses remain poorly understood. Furthermore, the utility of GPR146 as a diagnostic or prognostic marker for NSOI has not been conclusively demonstrated. We adopted a comprehensive analytical strategy, merging differentially expressed genes (DEGs) from the Gene Expression Omnibus (GEO) datasets GSE58331 and GSE105149 with immune-related genes from the ImmPort database. Our methodology combined LASSO regression and support vector machine-recursive feature elimination (SVM-RFE) for feature selection, followed by Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) to explore gene sets co-expressed with GPR146, identifying a significant enrichment in immune-related pathways. The tumor microenvironment's immune composition was quantified using the CIBERSORT algorithm and the ESTIMATE method, which confirmed a positive correlation between GPR146 expression and immune cell infiltration. Validation of GPR146 expression was performed using the GSE58331 dataset. Analysis identified 113 DEGs associated with GPR146, with a significant subset showing distinct expression patterns. Using LASSO and SVM-RFE, we pinpointed 15 key hub genes. Functionally, these genes and GPR146 were predominantly linked to receptor ligand activity, immune receptor activity, and cytokine-mediated signaling. Specific immune cells, such as memory B cells, M2 macrophages, resting mast cells, monocytes, activated NK cells, plasma cells, and CD8+ T cells, were positively associated with GPR146 expression. In contrast, M0 macrophages, naive B cells, M1 macrophages, activated mast cells, activated memory CD4+ T cells, naive CD4+ T cells, and gamma delta T cells showed inverse correlations. Notably, our findings underscore the potential diagnostic relevance of GPR146 in distinguishing NSOI. Our study elucidates the immunological signatures associated with GPR146 in the context of NSOI, highlighting its prognostic and diagnostic potential. These insights pave the way for GPR146 to be a novel biomarker for monitoring the progression of NSOI, providing a foundation for future therapeutic strategies targeting immune-metabolic pathways.

Biocompatible 3D-Printed Devices With Adipose Stem Cells in the Regenerative Process of Sciatic Nerve Lesions in Rodent Models: An Experimental Study.

Peripheral nerve injuries are a significant clinical challenge. The rat sciatic nerve serves as an ideal model for studying nerve regeneration. Extensive research has been conducted to unravel the intricate mechanisms involved in peripheral nerve regeneration, aiming to develop effective therapeutic strategies for nerve injury patients. Research including different types of materials that can be used as nerve guides like synthetic polymershave been investigated for their biocompatibility and molding properties. Among multiple stem cell types, adipose-derived stem cells (ASCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), and induced pluripotent stem cells (iPSCs) have shown neuroprotective and regenerative important properties. The purposes of our study were to develop a protocol for rat sciatic nerve injury treated with 3D-printed guide and adipose stem cells to investigate nerve regeneration through histologic examination and biomechanical characteristics of muscular tissue. We use 20 (100%) male Wistar rats, measuring between 350 g ± 35 g, whounderwent complete transection of the right sciatic nerve, resulting in a 1 cm defect. The group was separated into three subgroups: the first subgroup (n = 8) was treated with a 3D-printed guide with adiposestem cells, the second subgroup (n = 8) was treated with a 3D-printed guide without adiposestem cells, and the third subgroup (n = 4) was the control group. At four, eight, and 12 weeks, we measured with ultrasonography the grade of muscular atrophy. At 12 weeks, we harvested the sciatic nerve and performed a histological examination and mechanical investigation of the tibialis anterior muscle. On the examined specimen of the first subgroup, cross-sectioned nerve structures were present, surrounded by a mature fibro-adipose connective tissue, with blood vessels. In the second subgroup, no nerve structure was observed on the examined sections, but in the polymorphic inflammatory infiltrate and control group, no signs of regeneration were found. The present study shows a promising potential when utilizing adipose stem cell-based therapies for promoting peripheral nerve regeneration following large (>1 cm) nerve defects knowing that at this size, regeneration is impossible with known treatments.

Cytokine-determined mechanisms of the pathomorphological realization of gastroesophageal reflux disease against the background of autoimmune thyroiditis in young persons

The aim: to study the features of proinflammatory cytokine status and pathomorphological realization of gastroesophageal reflux disease (GERD) against the background of autoimmune thyroiditis (AIT) in young people.
 Materials and methods. Examinations involved 120 patients with GERD and AIT and 45 people with isolated GERD. The control group consisted of 20 volunteers matched by age, gender, and social status. All patients underwent esophagogastroduodenoscopy, histological study, comparative morphometry of the esophageal mucosa, and determination of proinflammatory cytokines’ levels: interleukin‑1β (IL‑1β), IL‑18, tumor necrosis factor‑α (TNF‑α).
 Results. The frequency of erosive GERD in the examined groups of patients did not statistically differ. At the same time, analysis of the structure of erosive GERD forms revealed a significant redistribution of esophagitis grades towards its enhancement in patients with comorbid pathology. The histological study showed that in patients with nonerosive GERD and AIT all the studied morphometric parameters had significantly deeper changes and exceeded similar indicators of the group with isolated GERD: epithelium total thickness 319.3±9.1 µm against 286.1±8.2 µm (p <0.01), epithelium basal layer thickness 79.6±3.2 µm versus 49.7±2.1 µm (p <0.01), connective tissue papillae height 224.8±7.3 µm against 172.7±4.6 µm (p <0.01), intercellular space 1.55±0.11 µm versus 1.12±0.09 µm (p <0.01). The presence of concomitant AIT was associated with a significant redistribution towards increased degrees of hyperplasia of the basal layer of the epithelium, elongation of the papillae, and leukocyte infiltration. The comorbidity of GERD and AIT in young people was associated with significant increase in the blood serum levels of proinflammatory cytokines in compared to isolated GERD: IL‑1β — 29.6 pg/ml versus 17.7 pg/ml (p <0.01), IL‑18—1763.4 pg/ml versus 614.6 pg/ml (p <0.01), TNF‑α — 7.6 pg/ml versus 5.2 pg/ml (p <0.01). Correlation analysis of the cytokine content and expressivity of certain morphometric parameters of the esophageal mucosa revealed the direct correlations.
 Conclusions. GERD and euthyroid AIT comorbidity in the student population is accompanied by significant redistribution of esophagitis grades towards its aggravation. The presence of concomitant AIT in patients with non‑erosive GERD leads to the significant intensification of the degree of epithelium basal layer hyperplasia, connective tissue papillae elongation, and polymorphic cellular inflammatory infiltration in comparison with isolated GERD, while these deviations demonstrate direct correlations with the levels of IL‑1β, IL‑18, and TNF‑α.

Glutamine metabolism-related genes and immunotherapy in nonspecific orbital inflammation were validated using bioinformatics and machine learning

BackgroundNonspecific orbital inflammation (NSOI) is an idiopathic, persistent, and proliferative inflammatory condition affecting the orbit, characterized by polymorphous lymphoid infiltration. Its pathogenesis and progression have been linked to imbalances in tumor metabolic pathways, with glutamine (Gln) metabolism emerging as a critical aspect in cancer. Metabolic reprogramming is known to influence clinical outcomes in various malignancies. However, comprehensive research on glutamine metabolism's significance in NSOI is lacking.MethodsThis study conducted a bioinformatics analysis to identify and validate potential glutamine-related molecules (GlnMgs) associated with NSOI. The discovery of GlnMgs involved the intersection of differential expression analysis with a set of 42 candidate GlnMgs. The biological functions and pathways of the identified GlnMgs were analyzed using GSEA and GSVA. Lasso regression and SVM-RFE methods identified hub genes and assessed the diagnostic efficacy of fourteen GlnMgs in NSOI. The correlation between hub GlnMgs and clinical characteristics was also examined. The expression levels of the fourteen GlnMgs were validated using datasets GSE58331 and GSE105149.ResultsFourteen GlnMgs related to NSOI were identified, including FTCD, CPS1, CTPS1, NAGS, DDAH2, PHGDH, GGT1, GCLM, GLUD1, ART4, AADAT, ASNSD1, SLC38A1, and GFPT2. Biological function analysis indicated their involvement in responses to extracellular stimulus, mitochondrial matrix, and lipid transport. The diagnostic performance of these GlnMgs in distinguishing NSOI showed promising results.ConclusionsThis study successfully identified fourteen GlnMgs associated with NSOI, providing insights into potential novel biomarkers for NSOI and avenues for monitoring disease progression.

A case of exuberant endoscopic presentation of asymptomatic eosinophilic colitis.

Eosinophilic colitis is a rare entity characterized by a broad range of gastrointestinal symptoms and idiopathic infiltration of eosinophils in the colon. This condition is most likely underreported due to the absence of standardized diagnostic criteria. We present the case of a 72-year-old man who underwent an outpatient colorectal cancer surveillance colonoscopy without gastrointestinal complaints. Colonoscopy revealed a diffuse micronodular pattern of the colonic mucosa, with histopathological analysis showing a polymorphic infiltrate rich in eosinophils in the lamina propria. The patient was kept under surveillance, with a repeat colonoscopy showing persistent endoscopic and histological findings consistent with eosinophilic colitis. The patient remains asymptomatic. This case is unique from both clinical and endoscopic perspectives due to the asymptomatic course of this rare condition and the illustrative iconography.

Solving the mystery of Reed Sternberg like cells in a composite Peripheral T Cell Lymphoma with Epstein Barr Virus and Epstein Barr Virus driven Lymphoproliferative Disorder

Abstract Introduction/Objective Nodal PTCL with EBV positivity can occasionally contain Reed Sternberg-like cells, and EBV- LPD can mimic Hodgkin lymphoma. Coexistence of these two unusual lymphomas in the same lymph node is very rare. We present a case of a 56-year-old male with Composite EBV+ PTCL NOS and EBV LPD, with positive B-cell gene rearrangement and negative T-cell gene rearrangement presenting a significant diagnostic challenge. Methods/Case Report A 56-year-old male with a history of abdominal tuberculosis presented with lethargy, fatigue, and poor appetite. Physical examination revealed generalized lymphadenopathy. CT scan confirmed lymphadenopathy in bilateral axilla, supraclavicular lymph nodes along with lytic lesions on illiac crest. Ill defined splenic lesions raised concerns for metastasis. Cervical lymph node and bone marrow biopsies were performed. Flow cytometry on the lymph node was not done due to tuberculosis history. Flow cytometry on the bone marrow showed an inverted CD4:CD8 ratio. H&E sections of the lymph node revealed a polymorphic lymphoid infiltrate with prominent Reed Sternberg-like cells. Immunohistochemical staining showed CD30-positive and CD45-negative large cells. T-cell and B-cell gene rearrangements were performed. Initially, B-cell gene rearrangements were positive, while T-gamma was negative. Further testing by IHC and morphological evaluation revealed two distinct cell populations, one with CD3, CD5, and CD7 positivity with partial weak positivity for PD1, CD43, and CD8 and the other consisting of B-cells expressing CD30, EBV, MUM1, and partial expression of BCL6 rare CD79a, and partial weak Pax5. Outside molecular testing showed positive T-cell gene rearrangements. The diagnosis of Composite EBV+ Peripheral T Cell Lymphoma, not otherwise specified, with cytotoxic profile along with EBV driven LPD was made. Bone marrow studies confirmed involvement by the same lymphoma. Results (if a Case Study enter NA) NA Conclusion Identifying EBV-positive Reed Sternberg-like cells in both EBV LPD and PTCL-NOS in a composite lymphoma can be challenging. In the absence of flow cytometry, a composite lymphoma can potentially be misdiagnosed, leading to under-treatment. Repeat testing can be helpful in case of any doubt. Although EBV-positive PTCL with cytotoxic profile and EBV-positive LPD has been reported, the combination of these two lymphomas together is exceedingly rare.

Angioimmunoblastic T-Cell Lymphoma with Concurrent EBV Viremia: A Challenging Case

Abstract Introduction/Objective Angioimmunoblastic T-cell lymphoma (AITL) represents only 1-2% of all non-Hodgkin lymphomas but is one of the most common non-cutaneous T-cell lymphomas. Although typically associated with latent Epstein Barr Virus (EBV) infection, recent studies have demonstrated the presence and prognostic impact of EBV viremia at the time of diagnosis. Here, we present a case of AITL in which the diagnosis was complicated by EBV viremia. Methods/Case Report A 41-year-old male presented to our hospital with generalized abdominal pain, diffuse lymphadenopathy, hepatomegaly, ascites, and diffuse body wall edema. A recent retroperitoneal lymph node biopsy reportedly demonstrated features suggesting an infectious process, and EBV PCR revealed a viral load of 141,050 copies/mL. A left axillary lymph node was excised, which demonstrated vascular proliferation and diffuse architectural effacement by a polymorphous infiltrate including variably sized lymphocytes with moderate to abundant clear cytoplasm, and occasional admixed neutrophils, plasma cells, and eosinophils. Immunohistochemical staining demonstrated an atypical CD4-positive, CD7-negative T-cell population in a vaguely nodular distribution, expressing Bcl-6, PD-1, ICOS, and CXCL13 without definite CD10 expression. CD21 immunostaining demonstrated markedly expanded follicular dendritic cell meshworks in a distribution similar to the atypical T-cell population. No B-cell or cytotoxic T-cell proliferation was seen, and in situ hybridization for EBV-encoded RNA (EBER ISH) demonstrated only scattered EBV- positive cells. Taken together, these findings supported a diagnosis of AITL over an atypical reaction to EBV infection. Next-generation sequencing demonstrated mutations in TET2, IDH2, and RHOA, further confirming the diagnosis. Results (if a Case Study enter NA) NA Conclusion AITL manifests with a diverse range of clinical symptoms and pathological features and may mimic infection. Additionally, acute EBV infection is well-known to mimic various lymphomas and has rarely been reported to mimic AITL. We present this case to raise awareness of the concurrent presentation of AITL with EBV viremia and to highlight features that may be helpful in distinguishing between the two.

Primary CNS EBV-positive post-transplant lymphoproliferative disorder with polymorphic and classic Hodgkin lymphoma features: A case report and literature review.

Post-transplant lymphoproliferative disorders (PTLD) are typically Epstein-Barr virus (EBV)-associated lymphoid or plasmacytic proliferations that occur when immunosuppressed after transplantation. Only 2 cases of primary central nervous system (PCNS) classic Hodgkin lymphoma PTLD and 1 case of PCNS Hodgkin lymphoma-like PTLD have been previously reported. A 59-year-old male presented with malaise, headaches, and dizziness; neuroimaging revealed a 1.7-cm right cerebellar mass and a 0.6-cm right frontal mass. Microscopic examination demonstrated a perivascular and parenchymal polymorphous infiltrate composed of lymphocytes (CD3-positive T cells and CD20-positive B cells), plasma cells, and macrophages. Focally, macrophages had a spindled morphology with a fascicular arrangement amounting to poorly formed granulomata. Mitoses were seen. Scattered large atypical cells were visualized with irregular hyperchromatic nuclei, reminiscent of lacunar cells, mononuclear Hodgkin and binucleate Reed-Sternberg (RS) cells. EBV in situ highlighted a significant number of small lymphoid cells as well as many large atypical forms. Large atypical cells were seen to co-express CD15 and CD30. To our knowledge, this is the first such case with hybrid polymorphic PTLD and classic Hodgkin lymphoma features and the first such case to arise following liver transplantation. This case highlights the histological and immunophenotypic spectrum of these lymphoid proliferations and the resulting challenges in diagnosis and definitive subtyping.

Preclinical safety study of local use of the directed ozone gas flow in abdominal surgery

Purpose of the study: to assess the patho-histological changes in the intact pancreas and parietal peritoneum against the background of the directed ozone gas flow.Material and methods. The prospective study was conducted in 54 adult male Wistar rats. In 1st and 2nd groups (n = 24, each) the left pancreatic lobe and parietal peritoneum, respectively, was treated with a 40 mg/L ozone gas stream at a rate of 2 L/min for 1.5 minutes. 1, 3, 30 and 120 days after the first operation 6 animals of each groups were sacrificed and tissue specimens were collected for histological analysis. In the control group (6 sham operated animals), tissue samples were collected 120 days after laparotomy.Results. A day after treatment with ozone gas stream, the pancreatic specimens of 1st group differed from the control in moderate and mild perivascular infiltration and edema. In the period from 3 to 120 days after exposure, the pancreatic specimens of 1st group and control did not differ significantly. Specimens of 2nd group differed from the control degree of edema and infiltration in the first 3 days, the level of proliferation of fibroblast-like cells and fibrosis in 120 days after treatment of the parietal peritoneum with a directed ozone gas stream.Conclusion. Local use of the directed ozone gas flow at a concentration of 40 mg/L at a rate of 2 L/min is accompanied by the same type of patho-histological changes from the intact pancreas and parietal peritoneum in the form of mild to moderate edema, perivascular polymorphic cell infiltration in the early period after exposure. Late parietal peritoneum reaction (moderate events fibroblast-like cell proliferation and fibrosis) requires additional safety studies of intraabdominal use of ozone-oxygen mixture.