Lymph Glands Research Articles

TCL1A-expressing B cells are critical for tertiary lymphoid structure formation and the prognosis of oral squamous cell carcinoma

BackgroundOral squamous cell carcinoma (OSCC) is a malignant tumor with a poor prognosis. Traditional treatments have limited effectiveness. Regulation of the immune response represents a promising new approach for OSCC treatment. B cells are among the most abundant immune cells in OSCC. However, the role of B cells in OSCC treatment has not been fully elucidated.MethodsSingle-cell RNA sequencing analysis of 13 tissues and 8 adjacent normal tissues from OSCC patients was performed to explore differences in B-cell gene expression between OSCC tissues and normal tissues. We further investigated the relationship between differentially expressed genes and the immune response to OSCC. We utilized tissue microarray data for 146 OSCC clinical samples and RNA sequencing data of 359 OSCC samples from The Cancer Genome Atlas (TCGA) to investigate the role of T-cell leukemia 1 A (TCL1A) in OSCC prognosis. Multiplex immunohistochemistry (mIHC) was employed to investigate the spatial distribution of TCL1A in OSCC tissues. We then investigated the effect of TCL1A on B-cell proliferation and trogocytosis. Finally, lentiviral transduction was performed to induce TCL1A overexpression in B lymphoblastoid cell lines (BLCLs) to verify the function of TCL1A.ResultsOur findings revealed that TCL1A was predominantly expressed in B cells and was associated with a better prognosis in OSCC patients. Additionally, we found that TCL1A-expressing B cells are located at the periphery of lymphatic follicles and are associated with tertiary lymphoid structures (TLS) formation in OSCC. Mechanistically, upregulation of TCL1A promoted the trogocytosis of B cells on dendritic cells by mediating the upregulation of CR2, thereby improving antigen-presenting ability. Moreover, the upregulation of TCL1A expression promoted the proliferation of B cells.ConclusionThis study revealed the role of B-cell TCL1A expression in TLS formation and its effect on OSCC prognosis. These findings highlight TCL1A as a novel target for OSCC immunotherapy.

Extracellular traps in skin lesions infected with lymphocystis disease virus in black rockfish (Sebastes schlegelii)

The lymphocystis disease (LCD), caused by Lymphocystis disease virus (LCDV), is a benign and self-limiting disease described in a many freshwater and marine fish species. Hypertrophic fibroblasts and extensive aggregation of inflammatory cells are characteristics of LCD. In the present study, small animal imaging and ultrastructural investigations were carried out on the lymphocystis nodules of black rockfish (Sebastes schlegelii) naturally infected with lymphocystis iridovirus, to assess pathology, and the exudate with particular attention to the formation of extracellular traps (ETs) in vivo. Ex vivo were examined by nodules sections and primary cells stimulation. By histopathological analysis, the nodules contained infiltrated inflammatory cells and extensive basophilic fibrillar filaments at the periphery of the hypertrophied fibroblasts. ETs were assessed in nodules samples using indirect immunofluorescence to detect DNA and myeloperoxidase. Moreover, LCDV was able to infect peritoneal cells of black rockfish in vitro and induce the formation of ETs within 4 h. In summary, this study proved that ETs are involved in the response to LCDV infection and may be involved in formation of lymphoid nodules. Taken together, the findings provide a new perspective to determine the impact factors on the growth of nodules.

Modeling Structural Elements and Functional Responses to Lymphatic-Delivered Cues in a Murine Lymph Node on a Chip.

Lymph nodes (LNs) are organs of the immune system, critical for maintenance of homeostasis and initiation of immune responses, yet there are few models that accurately recapitulate LN functions in vitro. To tackle this issue, an engineered murine LN (eLN) has been developed, replicating key cellular components of the mouse LN; incorporating primary murine lymphocytes, fibroblastic reticular cells, and lymphatic endothelial cells. T and B cell compartments are incorporated within the eLN that mimic LN cortex and paracortex architectures. When challenged, the eLN elicits both robust inflammatory responses and antigen-specific immune activation, showing that the system can differentiate between non specific and antigen-specific stimulation and can be monitored in real time. Beyond immune responses, this model also enables interrogation of changes in stromal cells, thus permitting investigations of all LN cellular components in homeostasis and different disease settings, such as cancer. Here, how LN behavior can be influenced by murine melanoma-derived factors is presented. In conclusion, the eLN model presents a promising platform for in vitro study of LN biology that will enhance understanding of stromal and immune responses in the murine LN, and in doing so will enable development of novel therapeutic strategies to improve LN responses in disease.

Histological Correlation between Tonsillar and Glomerular Lesions in Patients with IgA Nephropathy Justifying Tonsillectomy: A Retrospective Cohort Study.

Tonsillectomy with steroid pulse therapy (SPT) has been established as an effective treatment for immunoglobulin A nephropathy (IgAN) in Japan. However, the underlying mechanisms supporting tonsillectomy remain unclear. This study assessed palatine tonsils from 77 patients with IgAN, including 14 and 63 who received SPT before and after tonsillectomy, respectively. Tonsils from 21 patients with chronic tonsillitis were analyzed as controls. Specific tonsillar lesions were confirmed in patients with IgAN, correlating with active or chronic renal glomerular lesions and SPT. T-nodule and involution of lymphoepithelial symbiosis scores in tonsils correlated with the incidence of active crescents and segmental sclerosis in the glomeruli, respectively. The study revealed an essential role of the tonsil-glomerular axis in early active and late chronic phases. Moreover, the SPT-preceding group demonstrated no changes in the T-nodule score, which correlated with active crescent formation, but exhibited a considerable shrinkage of lymphatic follicles that produced aberrant IgA1. The study underscores the involvement of innate and cellular immunity in IgAN and advocates for tonsillectomy as a necessary treatment alongside SPT for IgAN, based on a stepwise process.

THE EFFECT OF GREEN TEA INFUSION (CAMELLIA SINENSIS) ON THE DIAMETER OF THE SPLEEN LYMPHATIC NODULUS OF MICE (MUS MUSCULUS) EXPOSED TO ELECTRIC CIGARETTE

E-cigarettes are the most widely used nicotine replacement therapy (NRT), particularly among young people. Exposure to e-cigarette vapor increases free radicals and suppresses the body's immune system. The accumulation of reactive oxygen species (ROS) in the spleen causes inflammation and tissue injury that decreases immune reactivity. It causes changes in the histoarchitecture of the spleen, including the lymphatic nodules. It might be repaired by the antioxidant and immunomodulatory activity of green tea that stimulates and enhances the immune system. Green tea polyphenols affect the production of cytokines along with the activation, proliferation, and differentiation of lymphocytes in the body. Increasing the diameter of the lymphatic nodules is an indicator of the immunomodulatory activity of green tea in mice exposed to e-cigarette vapor. The study design was a randomized post-test only controlled group with 27 sampled mice divided randomly into 3 groups, namely; P0 (e-cigarette vapor), P1 (e-cigarette vapor + green tea 0.020 g/bb/day), and P2 (e-cigarette vapor + green tea 0.040 g/bb/day). There were significant differences between the control and treatment groups, while between green tea doses of 0.020 g/bb/day and 0.040 g/bb/day was no significant difference. The study showed green tea infusion with an optimal dose of 0.020g/bb/day affected increasing the diameter of the spleen lymphatic nodules of mice exposed to e-cigarette vapor. Further research based on the difference in duration of infusion exposure and overall observation of the white pulp component are needed. Keywords : Green tea infusion, Lymphatic nodules, E-cigarette vapor.

Abstract PO4-25-01: Selective elimination of CD169+ macrophages in lymph nodes invaded by breast cancers

Abstract Lymph node metastasis is a prognostically significant factor in breast cancer, though the colonization mechanism of cancer cells in this immune cell-rich organ remains elusive. This study aimed to elucidate the impact of breast cancer on the lymph node immune cell landscape. Multiscale transcriptomic analyses were performed on both metastatic and non-metastatic lymph node samples from breast cancer patients with lymph node metastasis. Twenty laser-micro-dissected sections were obtained from 17 lymph nodes across six breast cancer patients at stages II–III, with each patient contributing both types of lymph nodes for direct comparison. Comparing the transcriptomes of paired lymph nodes with and without metastasis from the same patients revealed selective downregulation of CD169+ macrophage-related genes in metastatic lymph nodes. The spatial transcriptome indicated a potential depletion of CD169+ macrophages, initiators of anticancer immunity, from their residence (sinuses) in metastatic lymph nodes, while other principal immune cell types were unaltered. Mass spectrometry imaging revealed that the numbers of CD169+ macrophages were smaller in the metastatic lymph nodes than in the non-metastatic lymph nodes, suggesting that cancer cells uprooted CD169+ macrophages from the lymph nodes. Conversely, the count of B, T, Treg, and CD11c+ cells remained comparable in both lymph node types, albeit an enrichment of Treg cells around metastasized cancer tissues was observed. Additional immunohistochemistry analysis of 315 non-metastatic lymph nodes and 159 metastatic lymph nodes from 58 patients with breast cancer showed that a reduced CD169+ macrophage population was prevalent in various breast cancer subtypes. A subset of metastatic lymph nodes (37 out of 159) displayed a complete absence of detectable CD169+ macrophages. The data also depicted a gradual decline in CD169+ macrophages correlating with the pN classification, while no correlation was identified with pathological tumor size classification (pT) or metastasized cancer volume. The data suggest precedence of CD169+ macrophage elimination over other reported immune cell abnormalities, such as cell number and metabolic irregularities. CD169+ macrophages are a unique type of resident macrophages in the lymphoid organs that present cancer-derived antigens to CD8+ cells. The antigen-presenting role of CD169+ macrophages to T cells, a pivotal step in adaptive immunity, signifies the catastrophic implications of their suppression. This study underscores CD169+ macrophage suppression as a pronounced pathological phenotype in lymph nodes with breast cancer metastasis, thereby establishing it as a critical future therapeutic target. Citation Format: Yurina Maeshima, Tatsuki R. Kataoka, Alexis Vandenbon, Masahiro Hirata, Yasuhide Takeuchi, Yutaka Suzuki, Yukiko Fukui, Yumiko Ibi, Hironori Haga, Satoshi Morita, Masakazu Toi, Shinpei Kawaoka, Kosuke Kawaguchi. Selective elimination of CD169+ macrophages in lymph nodes invaded by breast cancers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-01.

Abstract PO4-22-10: Prognostic impact of preoperative lymph node diagnostic tools for patients with suspicious node positive breast cancer

Abstract (Abstract) Recently, the SOUND trial demonstrated the feasibility for omission of sentinel lymph node biopsy (SNB) in cases with negative ultrasound (US)-guided fine-needle aspiration cytology (FNA) of suspicious lymph nodes (LNs). An important consideration for omission of SNB depends on a highly accurate assessment of preoperative staging for axillary LNs. (Purpose) The purpose of this study was to investigate the impact of preoperative diagnostic tools for axillary lymph nodes (LNs) staging of early breast cancer. (Materials and Methods) A total of 3088 consecutive patients with operable breast cancer were retrospectively identified at our institution between April 2013 and March 2020. Patients with suspicious axillary LN of breast cancer were assessed using preoperative US and computed tomography (CT), underwent FNA or core needle biopsy (CNB). The inclusion criteria for both FNA and CNB were a cortical thickness [3 mm or abnormal morphological characteristics. Patients with biopsy-proven metastasis underwent axillary lymph node dissection (ALND), and those with a negative FNA or CNB underwent SNB. If the SNB was positive, ALND was performed. Diagnostic accuracy for SNB was calculated for both FNA and CNB. In addition, the patients in this study were divided into two groups as follows: the cN0-FNA negative group (suspicious LN but negative FNA) and the cN0-CNB group (suspicious LN but negative CNB). Overall survival (OS)and invasive disease survival(iDFS) was estimated by using the Kaplan-Meier method and compared by using the log-rank test. (Results) A number of patients with negative or suspicious metastasis US/CT findings of LNs were 3187, with 963 undergoing FNA and 395 undergoing CNB for suspicious LNs. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 63, 99, 99, 73, and 81% in FNA, and 87, 100, 100, 91 and 95% in CNB, respectively. SNB was performed in 207 (cN0-CNB group) of 395 CNB and 581 (cN0-FNA group) of 963 FNA patients. Two hundred and seven patients from the cN0-CNB group (T1ab; 42, T1c; 72, T2;84, T3;9 patients) treated with SNB were compared to 581 from the cN0-FNA group (T1ab;86, T1c;193, T2;278, T3;24 patients) in terms of number of LN metastasis. A number of patients with micrometastases, 1,2,3 or more than 4 positive LNs were 5(2%),7(3%),3(1%)9,3(1%) and 0 (0%) in cN0-CNB group, and 23(4%),67(12%),26(4%),12(2%) and 29 (5%) in cN0-FNA group, respectively. The significant difference in 5ys iDFS and OS was observed between CNB group and FNA group (94.2% vs.91.4%, p =0.04 and 99% vs. 95%, p=0.004, respectively). Conclusions The preoperative diagnosis of axillary LNs was influenced by the diagnostic tool used. CNB is a reliable method for the preoperative diagnosis of LN metastasis. The prognosis of early breast cancer with clinically metastasis-negative lymph nodes diagnosed by CNB is better than that by FNA. Table. Number of positive lymph nodes cN0-FNA (%) cN0-CNB (%) Total 207 100 581 100 0 189 91 424 73 micrometastasis 5 2 23 4 1 7 3 67 12 2 3 1 26 4 3 3 1 12 2 4 more than 0 0 29 5 Citation Format: Rikiya Nakamura, Shouko Hayama, Rikiya Nakamura, Naohito Yamamoto. Prognostic impact of preoperative lymph node diagnostic tools for patients with suspicious node positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-22-10.

Transient caspase-mediated activation of caspase-activated DNase causes DNA damage required for phagocytic macrophage differentiation

Phagocytic macrophages are crucial for innate immunity and tissue homeostasis. Most tissue-resident macrophages develop from embryonic precursors that populate every organ before birth to lifelong self-renew. However, the mechanisms for versatile macrophage differentiation remain unknown. Here, we use invivo genetic and cell biological analysis of the Drosophila larval hematopoietic organ, the lymph gland that produces macrophages. We show that the developmentally regulated transient activation of caspase-activated DNase (CAD)-mediated DNA strand breaks in intermediate progenitors is essential for macrophage differentiation. Insulin receptor-mediated PI3K/Akt signaling regulates the apoptosis signal-regulating kinase 1 (Ask1)/c-Jun kinase (JNK) axis to control sublethal levels of caspase activation, causing DNA strand breaks during macrophage development. Furthermore, caspase activity is also required for embryonic-origin macrophage development and efficient phagocytosis. Our study provides insights into developmental signaling and CAD-mediated DNA strand breaks associated with multifunctional and heterogeneous macrophage differentiation.

Erythroblastosis Transformation-Specific Regulated Gene 1 (ERG) Immunohistochemistry in the Diagnosis of Acute Myeloid Leukemia.

The erythroblastosis transformation-specific regulated gene 1 (ERG) is a transcription factor that can be used as an immunohistochemical (IHC) marker in the diagnosis and prognostication of malignancy.ERG was initially used in prostate cancer; however, it is a useful marker in extramedullary myeloid disease. Patients with acute myeloid leukemia (AML), dry bone marrow aspirate, and CD34, CD117-negative blast cells can be in a diagnostic dilemma. This audit aimed to (a) validate ERG IHC in bone marrow trephine samples, (b) quantify ERG IHC positivity in an AML cohort, and correlate concordance with CD34 and CD117 IHC, when available, and (c) to see whether ERG is a useful adjunct in the diagnosis of cases of AML. A retrospective audit was completed of all new and relapsed cases of AML over one year at a single center. For inclusion, patients needed a trephine specimen at presentation, and all had ahematoxylin and eosin(H&E) specimen, ERG IHC, and at least one or both of CD34and CD117 IHC. Four pathologists independently assessed the stains quantitatively and qualitatively in comparison to the morphology seen on the H&E sample. The kappa value was used to assess agreement. Seventeen patients with AML met the inclusion criteria. All specimens had H&E, CD34, and ERG stains; 9/17 (53%) had CD117 IHC. ERG demonstrated high concordance with blast cells on H&E morphology, with a high agreement among pathologists. Qualitatively, pathologists recognized that ERG spared lymphoid nodules; however, it also stained granulocytes at various maturation stages. ERG is a sensitive marker for the diagnosis of AML. ERG can help visualize blast cells that have been confirmed by ancillary tests. More research into the utility of ERG in AML diagnostics is recommended.

Evaluation of Sensitivity and Specificity of Ultrasound-Guided FNA of Suspicious Axillary Lymph Nodes in Patients with Breast Cancer

Background: The axillary lymph node status in breast cancer is a major prognostic factor in survival and establishing a personalized treatment scheme. The ultrasound-guided fine needle aspiration (US-FNA) is a method for taking a lymph node sample. It allows physicians to decide how to manage the axilla. Objectives: This study was conducted to investigate the sensitivity of the US-FNA technique on suspicious axillary lymph nodes with a thickness of 3 to 6 mm in breast cancer patients. Methods: In a cross-sectional study, all the patients were subjected to preoperative ultrasound evaluation of the axilla to determine the presence of lymph nodes suspicious of malignancy. In cases where the suspicious lymph node cortex size was between 3 and 6 mm, US-FNA was performed. After surgery, the frozen section of the biopsy sample was examined histologically and compared with fine needle aspiration (FNA) cytology results. Results: A total of 102 patients were examined in the study. FNA test results indicated that 46 subjects had axillary malignant tissue, and benign cases summed 56. Also, the final results of frozen section surgical histopathology identified 46.1% of patients with involved lymph nodes. The sensitivity and specificity of FNA were 93.62% and 96.36%, respectively. Also, the overall diagnostic accuracy was 95.1%. Conclusions: This study showed that the sensitivity, specificity, and accuracy were more than 90% for the ultrasound-guided FNA test in identifying involved lymph nodes in patients with breast cancer. Therefore, the results of this test can be considered clinically reliable. However, there is still a need to examine the sensitivity and specificity of this method in identifying lymph node involvement.

Participation of the spleen in the neuroinflammation after pilocarpine-induced status epilepticus: implications for epileptogenesis and epilepsy.

Epilepsy, a chronic neurological disorder characterized by recurrent seizures, affects millions of individuals worldwide. Despite extensive research, the underlying mechanisms leading to epileptogenesis, the process by which a normal brain develops epilepsy, remain elusive. We, here, explored the immune system and spleen responses triggered by pilocarpine-induced status epilepticus (SE) focusing on their role in the epileptogenesis that follows SE. Initial examination of spleen histopathology revealed transient disorganization of white pulp, in animals subjected to SE. This disorganization, attributed to immune activation, peaked at 1-day post-SE (1DPSE) but returned to control levels at 3DPSE. Alterations in peripheral blood lymphocyte populations, demonstrated a decrease following SE, accompanied by a reduction in CD3+ T-lymphocytes. Further investigations uncovered an increased abundance of T-lymphocytes in the piriform cortex and choroid plexus at 3DPSE, suggesting a specific mobilization toward the Central Nervous System. Notably, splenectomy mitigated brain reactive astrogliosis, neuroinflammation, and macrophage infiltration post-SE, particularly in the hippocampus and piriform cortex. Additionally, splenectomized animals exhibited reduced lymphatic follicle size in the deep cervical lymph nodes. Most significantly, splenectomy correlated with improved neuronal survival, substantiated by decreased neuronal loss and reduced degenerating neurons in the piriform cortex and hippocampal CA2-3 post-SE. Overall, these findings underscore the pivotal role of the spleen in orchestrating immune responses and neuroinflammation following pilocarpine-induced SE, implicating the peripheral immune system as a potential therapeutic target for mitigating neuronal degeneration in epilepsy.

Developmental characteristics of aggregated lymphoid nodules area in the abomasum of fetal Bactrian camels (Camelus bactrianus)

BackgroundBactrian camel is one of the important economic animals in northwest China. They live in arid desert, and their gestation period is about 13 months, which is longer than other ruminants (such as cattle and sheep). The harsh living conditions have made its unique histological characteristics a research focus. Aggregated lymphoid nodules area (ALNA) in the abomasum of Bactrian camels, as one of the most important sites for the induction of the immune response, provide a comprehensive and effective protective role for the organism, and their lack of information will affect the feeding management, reproduction and epidemic prevention of Bactrian camels. In this study, the histological characteristics of the fetal ALNA in the abomasum of Bactrian camels at different developmental gestation have been described by using light microscopy and histology .ResultsThe ALNA in the abomasum of the Chinese Alashan Bactrian camel is a special immune structure that was first discovered and reported by Wen-hui Wang. To further establish the developmental characteristics of this special structure in the embryonic stage, the abomasum ALNA of 8 fetuses of Alashan Bactrian camels with different gestational ages (5~13 months) were observed and studied by anatomy and histology. The results showed that the aggregation of reticular epithelial cells (RECs) surrounded by a very small number of lymphoid cells was detected for the first time in the abomasum of fetal camel at 5 months gestation, which was presumed to be primitive ALNA. At 7 months gestation, the reticular mucosal folds region (RMFR) appeared, but the longitudinal mucosal folds region (LMFR) was not significant, and histological observations showed that there were diffusely distributed lymphocytes around the RECs. At 10months gestation, RMFR and LMFR were clearly visible, lymphoid follicles appeared in histological observation, lymphocytes proliferated vigorously. By 13 months, the volume of lymphoid follicles increased, forming the subepithelial dome (SED), and there was a primitive interfollicular area between the lymphoid follicles, which contained high endothelial vein (HEV), but no germinal center (GC) was found. In summary, ALNA of Bactrian camels is not fully mature before birth.ConclusionsGenerally, the small intestine PPs of ruminants (such as cattle and sheep) is already mature before birth, while the ALNA in the abomasum of Bactrian camels is not yet mature in the fetal period. During the development of ALNA in Bactrian camel, the development of lymphoid follicles extends from submucosa to Lamina propria. Interestingly, the deformation of FAE changes with age from simple columnar epithelium at the beginning of pregnancy to Simple cuboidal epithelium, which is opposite to the FAE deformation characteristics of PPs in the small intestine of fetal cattle and sheep. These results are the basis of further research on the specificity of ALNA in the abomasum of Bactrian camels.

Selpercatinib for treating recurrent mixed medullary and follicular cell-derived thyroid carcinoma: a case report

BackgroundMixed medullary and follicular cell-derived thyroid carcinoma (MMFCC) is characterized by the coexistence of follicular and C cell–derived tumour cell populations within the same lesion. Due to its rarity, its etiology and clinical course remain unclear, and treatment for advanced or recurrent cases has not been established.Case presentationWe report a case of MMFCC treated with selpercatinib. The patient was a 69-year-old male presenting with tumors in the right thyroid lobe and in the upper mediastinum. Fine-needle aspiration (FNA) cytology of the right thyroid lobe tumor revealed a medullary carcinoma; germline RET mutations were not detected. After resection of the right thyroid lobe with central node dissection, rapid intraoperative diagnosis of the mediastinal mass confirmed malignancy, leading to total thyroidectomy with excision of the upper mediastinal tumor. Histologically, the tumor in the right thyroid lobe and the pretracheal lymph node revealed a mixture of medullary and follicular carcinoma components, diagnosed as MMFCC. The mediastinal lymph node exhibited only medullary carcinoma components. At 11 months postoperatively, computed tomography scans showed enlargement of the right supraclavicular and upper mediastinal lymph nodes. FNA cytology of the right supraclavicular lymph node suggested the recurrence of medullary thyroid carcinoma. The gene panel testing (The Oncomine Dx Target Test Multi-CDx system®, Thermo Fisher SCIENTIFIC) of metastatic lymph node revealed RET somatic mutation (M918T). Treatment with selpercatinib was initiated, and both the cervical and mediastinal lymph nodes showed a reduction in size.ConclusionsWe report a rare case of selpercatinib use for MMFCC. Since RET mutations may occur frequently in MMFCC, selpercatinib could be effective in treating MMFCC.

Effect of Selenium-Yeast supplementation on gut microbiome, intestinal histomorphology and immunity in broilers

Selenium-yeast was mixed with the basal diet of treatment groups of birds at the dose rate of 0.15 mg/kg diet in treatment-I (T-I), 0.225 mg/kg in treatment-II (T-II) and 0.30 mg/kg in treatment-III (T-III) group. The body weight and weekly weight gain increased and, feed conversion ratio improved significantly (p<0.05) in the T-III group as compared to control group. The number of goblet cells, lymphatic nodules in the intestine was more in treated birds. The villi height and crypts depth and their ratio were significantly highest in T-III group. Bursal morphology significantly improved and the number of Hassall’s corpuscle, macrophages and plasma cells were more frequent in treated birds. Among the lymphoglandular organs, the maximum IL-10 positive cells were found in the caecum and Bursa of Fabricius (BF). Among the groups, T-III group showed weak to nil IL-10 reaction. When compared between the days, BF and spleen showed better IL-10 positive reaction on 7th day but in caecal tonsil and thymus, the better reaction was on 35th day. The expression of IL-10 in the lymphoglandular organs was significantly (p<0.05) lower and T-III had minimum expression. T-II and T-III groups were better than T-I and control groups for enhancing humoral immunity against Newcastle disease virus, reduction of gut Escherichia coli, Salmonella and increased gut Bifidobacterium spp. In conclusion, supplementation of Se-yeast to the poultry diet at the dose rate 0.30 mg/kg improved the growth performance and guts microbial health, and enhanced the immunity of poultry birds.

The Morphology of Nasal Polyps in Different Age Groups: Histopathological Features.

Nasal polyps (NPs) represent the end-stage manifestation of chronic rhinosinusitis (CRS), a relatively common pathological condition encountered in all ages of life. The aim of our study was to evaluate the histological features and inflammatory cellular components of NPs in a retrospective cohort (143 cases) of pediatric, adult and elderly populations in order to discuss the possible morphological age-related differences statistically documented. In the pediatric group, the inflammatory infiltrate presented many eosinophils mixed with lymphocytes, while in the adult population, lymphocytes and plasma cells were mainly evident, frequently with a perivascular distribution or with the formation of subepithelial lymphoid nodules. In the elderly population, inflammation was less evident and was associated with cavernous-like angecthatic structures with thrombotic stratification. Nearly all morphological findings exhibited statistically significant values among differently aged subgroups. Our results support the presence of histological specificities of NPs at different ages of life, providing new insight into the etiopathogenesis of NPs. The future role of biological therapies, mainly in cases refractory to already available standard medical and surgical treatments, may be analyzed by a prospective study using a larger cohort with a long-term evaluation also in relation to a possible relapse.

Determination of the Lymphadenopathy in Child Care

The majority of the time, swollen lymph nodes are a sign that your body is battling a virus or bacterial infection. Immune cells, viruses or bacteria, and fluid fill the nodes, increasing their size. Rarely, other, graver diseases can also result in swollen lymph nodes. Lymphadenopathy is fairly typical. Typically, it is not clinically significant in and of itself. However, it might indicate a serious underlying illness. For clinicians, the challenge is to avoid aggressive examination and biopsy of the majority of children while providing prompt, accurate for kids with serious underlying diseases. Lymphadenopathy is the term for swollen glands or swelling of the lymph nodes. The lymph glands are part of the immune system and help fight infections and other disease. They are enlarged when the body is fighting infection or other diseases. In children its to be able to feel some lymph nodes small, movable lumps under the skin. But if the nodes get bigger than usual, your child may have an infection or other problem. In most cases, lymphadenitis clears up quickly with proper treatment but it may take more time for lymph nodes swelling to go away. Be sure to let your healthcare provider know if your lymphadenitis symptoms come back. The most common treatment for swollen lymph nodes caused by a bacterial infection is antibiotics.

Formation of recurring transient Ca2+-based intercellular communities during Drosophila hematopoiesis

Tissue development occurs through a complex interplay between many individual cells. Yet, the fundamental question of how collective tissue behavior emerges from heterogeneous and noisy information processing and transfer at the single-cell level remains unknown. Here, we reveal that tissue scale signaling regulation can arise from local gap-junction mediated cell-cell signaling through the spatiotemporal establishment of an intermediate-scale of transient multicellular communication communities over the course of tissue development. We demonstrated this intermediate scale of emergent signaling using Ca2+ signaling in the intact, ex vivo cultured, live developing Drosophila hematopoietic organ, the lymph gland. Recurrent activation of these transient signaling communities defined self-organized signaling "hotspots" that gradually formed over the course of larva development. These hotspots receive and transmit information to facilitate repetitive interactions with nonhotspot neighbors. Overall, this work bridges the scales between single-cell and emergent group behavior providing key mechanistic insight into how cells establish tissue-scale communication networks.

A Systematic Review and Meta-Analysis of 29 Studies Predicting Diagnostic Accuracy of CT, MRI, PET, and USG in Detecting Extracapsular Spread in Head and Neck Cancers.

Extracapsular spread (ECS) is the extension of cancer cells beyond the lymph node capsule and is a significant prognostic factor in head and neck cancers. This meta-analysis compared the diagnostic accuracy of CT, MRI, PET, and USG in detecting ECS in head and neck cancers. The authors conducted a systematic review and meta-analysis of studies that compared the diagnostic accuracy of CT, MRI, PET, and USG in detecting ECS in head and neck cancers. They included studies that were published between 1990 and December 2023 and that used histopathology as the reference standard for ECS. The pooled sensitivity and specificity of CT scan were 0.63 (95% CI = 0.53-0.73) and 0.85 (95% CI = 0.74-0.91), respectively. The pooled sensitivity and specificity of MRI were 0.83 (95% CI = 0.71-0.90) and 0.85 (95% CI = 0.73-0.92), respectively. The pooled sensitivity and specificity of PET were 0.80 (95% CI = 0.74-0.85) and 0.93 (95% CI = 0.92-0.94), respectively. The pooled sensitivity and specificity of USG were 0.80 (95% CI = 0.68-0.88) and 0.84 (95% CI = 0.74-0.91), respectively. MRI had significantly higher sensitivity than CT scan (p-0.05). The specificity of CT and MRI was not significantly different (p-0.99). PET scan had the highest specificity among all imaging modalities. MRI is the most accurate imaging modality for detecting ECS in head and neck cancers. CT scan is a reasonable alternative, but PET scan may be considered when high specificity is required. USG may not add any further benefit in detecting ECS.

Diffuse large B-cell lymphoma with DNA copy number changes in a Japanese black calf

A 2-month-old Japanese Black calf exhibited mandibular and superficial cervical lymph node swelling. Fine needle aspiration cytology of the superficial cervical lymph node revealed large lymphoblast-like cells with mitoses. Hematological examination revealed remarkable lymphocytosis with atypical lymphocytes. Increased activities of serum total lactate dehydrogenase and thymidine kinase were detected. At necropsy, generalized swelling of lymph nodes was observed. Histopathological analysis revealed diffuse proliferation of medium-sized round centroblastic neoplastic cells that were positive for CD20, CD79α, PAX5, and BLA-36, and negative for CD3, CD5, CD10, and CD34. The calf was diagnosed with centroblastic diffuse large B-cell lymphoma (DLBCL) based on these findings. Analysis of DNA copy number variation revealed an increased copy number for the GIMAP family relative to that in healthy cattle. Moreover, decreases in copy numbers of GBP-1, MIR3141, OR5P1E, and PTPRG relative to those in healthy cattle were also observed. Because DNA copy number variation represent a major contribution to the somatic mutation landscapes in human tumors, these findings suggest that DNA copy number changes might have contributed to the onset of DLBCL in the present case.

171 Not Just a Matter of Retained Embryonic Spinal Cord: Histopathology of the Filum Terminale in Tethered Cord Syndrome

INTRODUCTION: We present a large consecutive series of patients with tethered cord syndrome who underwent resection of the filum terminale (FT) and the histopathologic findings as analyzed by the neuropathologists. METHODS: FT specimens obtained from a consecutive series of 288 pediatric and adult patients that underwent spinal cord releases performed at a single academic institution from 2013-2021 were analyzed retrospectively (IRB #787945). Hematoxylin and eosin (HE) and immunohistochemistry staining was performed to study the spectrum of cells known to reside in connective tissues. RESULTS: The most common structures included peripheral nerves (97.6%), ependymal cells (70.8%), ganglion cells (38.5%), and neuropil (15.3%). Cases with excess ependymal cells were associated with ependymal canals (5.9%), ependymal cysts (3.1%), and one case with extensive ependymal “proliferation” (0.3%). With regards to the inflammatory cellular findings, eleven specimens (3.8%) contained scattered or accumulated lymphocytes, macrophages, mast cells, macrophage-derived giant cells, and a secondary lymph follicle in one patient. 36 patients (12.5%) had increased vascularity with enlarged capillaries. Nine patients (3.1%) had an associated type of vascular malformation. A group of specimens included dystrophic calcification within the FT (7.6%). CONCLUSIONS: Both vascular and inflammatory changes along with calcifications have been overlooked as possible associated histologic secondary to mechanical stress on the FT. Additionally, vascular anomalies could alter the filum’s mechanical properties due to venous congestion.