Aggregates Of Lymphoid Cells Research Articles

Tertiary Lymphoid Structures Are Related to Inflammatory Progression and Bone Loss in Human Apical Periodontitis

IntroductionBone loss is strongly associated with the immunologic milieu in apical periodontitis (AP). Tertiary lymphoid structures (TLSs) are organized lymphoid cell aggregates that form in nonlymphoid tissues under persistent inflammatory circumstances. To date, there has been no relevant report of TLSs in periapical lesions. This work aimed to investigate the formation and potential function of TLSs in AP. MethodsTissues from human apical lesions (n = 61) and healthy oral mucosa (n = 5) were collected. Immunohistochemistry and multiplex immunofluorescence were used to detect the formation of TLSs. Correlation analyses were performed between clinical variables and TLSs. In addition, immunohistochemistry was used to evaluate the expression of interleukin-1 beta, interleukin-6, receptor activator of nuclear factor kappa-B ligand, and macrophage subsets in the apical lesions. ResultsPeriapical granulomas (n = 24) and cysts (n = 37) were identified by histologic evaluation. TLSs, composed of B-cell and T-cell clusters, developed in periapical granulomas and radicular cysts. The CXC-chemokine ligand 13, its receptor CXC-chemokine receptor 5, follicular dendritic cells, and high endothelial venules were localized in TLSs. The quantity and size of TLSs were positively associated with bone loss in AP. Moreover, proinflammatory cytokines and macrophage subsets were also substantially elevated in TLS regions of apical lesions. ConclusionsThe formation of TLSs in periapical granulomas and cysts was closely associated with persistent immune responses and bone loss in apical lesions. TLSs provide an updated insight into the complicated immune response process in AP.

Evaluation of feed utilization, immune response and disease resistance in striped catfish, Pangasianodon hypophthalmus (Sauvage 1878) fed with a novel Aeromonas hydrophila biofilm vaccine

Striped catfish, Pangasianodon hypophthalmus was immunized with Biofilm (BF) and Free cell (FC) of Aeromonas hydrophila vaccine at 1010 CFU g−1 for 20 days and monitored for growth parameters, immune responses and disease resistance up to 60 day post vaccination (dpv). Pangasius catfish in the BF vaccinated group had considerably higher growth and feed utilization than the FC vaccinated and unvaccinated groups (p < 0.05). Biofilm vaccinated group showed a significant increase (p < 0.05) in the mean weight gain (46.91 ± 0.59) than the FC (35.94 ± 0.21) and unvaccinated group (34.92 ± 0.35). The vaccinated fishes were challenged with A. hydrophila at 107 CFU/ml. Significant higher relative percentage survival (RPS) was recorded with BF (84.21 ± 1.49%) compared to that with FC (33.33 ± 1.21%). Polyclonal antibody-based ELISA was used to quantify the antibody titre. BF vaccinated group showed significantly higher antibody titer compared to other treatments (p < 0.05). Moreover, higher haematological parameters recorded in the present study were differentially stimulated by the oral administration of A. hydrophila biofilm vaccine. The mean total protein, albumin, and globulin levels of the BF vaccine groups were significantly higher (p < 0.05) than the mean total protein, albumin, and globulin contents of the unvaccinated group. Furthermore, biochemical stress parameters (SGPT, SGOT) in the vaccinated groups showed an incremental trend in the early days of the experimental period. However, the values were significantly lower (p < 0.05) in the biofilm group on 20 dpv onwards indicating improved health condition. Vaccinated BF fishes showed gut associated lymphoid tissues (GALT) within the laminar propria of mid gut. But in FC group fishes showed less aggregation of lymphoid cells. The unvaccinated control fish had no lymphoid cell aggregation in their intestines. The findings of the current research suggested that biofilm vaccine has the capability to be one of the potential oral vaccines in striped catfish against A. hydrophila infection.

Effect of Oral Administration of 3-Methylmorphine (Codeine) Induced Renal Toxicity in Adult Wistar Albino

Codeine (3-Methylmorphine) is the most common opiate consumed worldwide, it is widely used for its analgesic, antitussive and antidiarrheal activities. The study aims to determine the effect of oral administration of codeine induced renal toxicity in adult Wistar Albino Rats. Twenty albino rats weighing between 150-200g were used. Animals were divided into 4 groups (A, B, C and D). Group A served as the control group. Group B received 30mg/kg, group C received 60mg/kg and group D received 90mg/kg codeine orally for 28 days. Data obtained were calculated for one-way analysis of variance (ANOVA), followed by a Post Hoc test. Results were expressed as mean ± standard error of the mean. Statement of differences was based on significance level at p&lt;0.05. The results showed a slight decrease in the mean values of Na+ , Cl- , and HCO3 – levels which are not significant, while K+ level showed an increase in group B and C followed by a decrease in group D which were not statistically significant (p&lt;0.05). Creatinine level did not show any variation when compared with the control group but there was an increase in urea level which was also not statistically significant at p&lt;0.05. Photomicrographs of rat’s kidneys in the treatment group showed; degeneration of the glomerulus, hydrophobic changes in the renal tubular lumen, fatty tissue, multi-focal interstitial haemorrhages, infiltration of inflammatory lymphoid cells, mild mononuclear cells infiltration in the renal cortex and mass aggregation of lymphoid cells in the cellular medullar when compared to control.

Tertiary lymphoid structures (TLS) identification and density assessment on H&E-stained digital slides of lung cancer.

Tertiary lymphoid structures (TLS) are ectopic aggregates of lymphoid cells in inflamed, infected, or tumoral tissues that are easily recognized on an H&E histology slide as discrete entities, distinct from lymphocytes. TLS are associated with improved cancer prognosis but there is no standardised method available to quantify their presence. Previous studies have used immunohistochemistry to determine the presence of specific cells as a marker of the TLS. This has now been proven to be an underestimate of the true number of TLS. Thus, we propose a methodology for the automated identification and quantification of TLS, based on H&E slides. We subsequently determined the mathematical criteria defining a TLS. TLS regions were identified through a deep convolutional neural network and segmentation of lymphocytes was performed through an ellipsoidal model. This methodology had a 92.87% specificity at 95% sensitivity, 88.79% specificity at 98% sensitivity and 84.32% specificity at 99% sensitivity level based on 144 TLS annotated H&E slides implying that the automated approach was able to reproduce the histopathologists’ assessment with great accuracy. We showed that the minimum number of lymphocytes within TLS is 45 and the minimum TLS area is 6,245μm2. Furthermore, we have shown that the density of the lymphocytes is more than 3 times those outside of the TLS. The mean density and standard deviation of lymphocytes within a TLS area are 0.0128/μm2 and 0.0026/μm2 respectively compared to 0.004/μm2 and 0.001/μm2 in non-TLS regions. The proposed methodology shows great potential for automated identification and quantification of the TLS density on digital H&E slides.

Hazards of Chronic Exposure to Nonylphenol: Concomitant Effect on Non-alcoholic Fatty Liver Disease in Male Albino Rats

BACKGROUND: Chronic exposure to environmental endocrine disruptors like nonylphenol (NP), has been shown in previous studies to predispose to non-alcoholic fatty liver disease. METHODS: In this work, forty adult male albino rats were divided into four groups, a high sucrose-high-fat diet (HSHFD) group, a group receiving 20 μg/kg/day of NP, an NP + HSHFD group, and a control group. The rats were sacrificed on day 60 after anesthetization. RESULTS: Biochemical tests indicated that serum transaminases (alanine aminotransferase, aspartate aminotransferase) were significantly increased in the NP + HSHFD group. Lipid metabolism was most disrupted in the NP + HSHFD with a highly significant increase (p &lt; 0.001) of serum cholesterol, triglyceride, and low-density lipoprotein cholesterol compared to other groups. Heme oxygenase 1 showed the highest expression in the NP + HSHFD group, with a highly significant difference in comparison with the other groups (p &lt; 0.001). Histopathological studies revealed fatty changes and dilatation in the central vein in the HSHFD group. Lymphoid cell aggregates were detected in the NP group. Massive inflammation and degeneration were revealed in the NP + HSHFD group. There was also marked expression of the apoptotic protein caspase-3 in the NP + HSHFD group. CONCLUSION: In conclusion, exposure to a 20 μg/kg/day of NP induced oxidative stress leading to non-alcoholic steatohepatitis.

An Unusual Riddle of Thyroid Swelling; Hodgkin’s Lymphoma Masquerading as Riedel’s Thyroiditis

Introduction: Thyroid swellings are one of the most common encountered endocrinological presentations however the prevalence of malignancy is about 4-6.5%. Hodgkin lymphomas usually present as neck swelling in form lymphadenopathy and Hodgkin disease affecting the thyroid gland is extremely rare (1-2.5% of all lymphomas). It usually occurs in middle age and has predilection for female gender. It can pose a diagnostic challenge with the histology of sclerosing fibrosis mimicking Riedel’s thyroiditis; another rare cause of stony hard goitre. Case History: A 39yr old female presented with rapidly enlarging painful thyroid mass. She complained of mild dysphagia but denied to have dyspnoea, dysphonia wheeze or stridor. There was no history of weight loss, B symptoms or any significant past illness. Clinically and biochemically she was euthyroid with normal TSH 0.73mU/l(0.35-3.50), Free thyroxine 13pmol/L (8-21), Free T3 3.9pmol/L (3.8-6.0). Blood count showed mild neutrophilia 8.21 (2-7x109/L). IGG subclasses 1-4 were all with normal limits. Initial Ultrasonography demonstrated 4.6 X 3.6cm U3 thyroid nodule extending retrosternally. FNA x2 was THY. Core biopsy demonstrated dense core of fibrous tissue with crushed aggregates of mature lymphoid cells and mixed neutrophils and histiocytes in keeping with fibro inflammatory process suggestive of Riedel’s thyroiditis. Patient was initiated on Prednisolone 100mg OD by the ENT surgeons after MDT discussion and patient had some symptomatic improvement in pain but no discernible reduction in size. Due to side effects from steroids she was referred to endocrinology department. Tamoxifen 20mg BD was started for symptom management. CTNCAP was organised to rule out lymphoproliferative disorder which was negative barring the known thyroid mass. She had no response to Tamoxifen either hence she underwent surgical resection. Surgical resection deemed very difficult due to mass infiltrating the strap muscles and neck vasculature hence wedge resection of the isthmus was done. Histology now revealed bands of dense fibrous tissue with admixed large lymphoid cells showing enlarged, red nucleoli. Immunohistochemistry of the large atypical lymphoid cells expressed CD30, CD15, MUM1, PAX5, CD20, CD79a and BCL6 and diagnosis was revised to Classic Hodgkin lymphoma, nodular sclerosis subtype. She was then referred to haematologist who initiated ABVD chemotherapy and her latest FDG PET scan shows complete metabolic response with significant reduction in the thyroid mass to 17mm X16 mm. Conclusion: Primary thyroid lymphoma can mimic Riedel’s and other forms of fibrosing thyroiditis. Most lymphomas arise from Hashimoto’s thyroiditis. Stony hard neck swellings are difficult to FNA and even core biopsy may not reveal the diagnosis, hence surgical resection and histological diagnosis should be sought earlier as most lymphomas respond well to chemotherapy.

Gastric Mucosa-associated Lymphoid Tissue Lymphoma: An Important Differential Diagnosis for a Rapidly Growing Gastric Subepithelial Tumor - A Case Report and Literature Review

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade lymphoma with a long median survival time because of its low proliferation rate. A 75-year-old man was referred to the hospital for hematemesis. Upper endoscopy revealed a 30-mm subepithelial tumor (SET). Abdominal CT and EUS revealed a homogeneously hypoechoic lesion arising from the second layer of the stomach, without distant metastasis. Laparoscopic wedge resection was performed. On microscopic examination, the tumor showed diffuse aggregation of small lymphoid cells with abnormal architecture. Neoplastic cells showed positive reactivity for CD20 and prominent lymphoepithelial lesions were observed. The urease breath test was also conducted, with a negative result. Our final diagnosis was &lt;i&gt;Helicobacter pylori&lt;/i&gt;-negative MALT lymphoma (Ann Arbor classification I&lt;sub&gt;E2&lt;/sub&gt;), which is a rapidly growing SET pattern. This case highlights the importance of including gastric MALT lymphoma as a differential diagnosis for rapidly growing gastric SETs.

Development and organization of pulmonary lymphoid aggregates after Klebsiella pneumoniae infection of the murine respiratory tract

Abstract Klebsiella pneumoniae is a worrisome nosocomial pathogen given the widespread emergence of antibiotic resistant strains. Little is known about the host immune response to K. pneumoniae; however, it has recently been shown that aggregates of lymphoid cells can be found in murine lungs 4 weeks after surviving K. pneumoniae pulmonary infection. Others have characterized pulmonary collections of lymphoid cells in response to other pathogens and coined them induced bronchus-associated lymphoid tissue (iBALT). iBALT is believed to assist in protection against re-infection. In our nonlethal model of K. pneumoniae, mice that survive the primary infection and exhibit these structures are indeed protected from K. pneumoniae challenge. To further characterize the development and organization of these structures, pulmonary immune cell populations were analyzed post-infection by flow cytometry, histology, and immunofluorescence. As expected, pulmonary neutrophil populations increase over the first 10 days post-infection. T cells appear to rapidly expand between 7 and 10 days post-infection and both CD4+ and γδ T cell subsets make up the majority of this population. Immunofluorescent imaging of lymphoid aggregates demonstrate that CD4+ and γδ T cells are found within these structures at early time-points. Experiments using TCRβδ−/− mice lacking T cells reveals the absence of lymphoid aggregates 28 days post-infection, suggesting that T cells are essential in the initial formation and development of these structures.

Impact Effect of Methyl Tertiary-Butyl Ether "Twelve Months Vapor Inhalation Study in Rats".

Simple SummaryThe detection of major blood-based markers for cancer requires expensive blood tests. Therefore, finding simple and effective blood-based markers is of great interest. The present results suggested that CA II, CA I, and peroxiredoxin2 could be utilized as potential biomarkers for the early detection of tracheal and lung cancer.We investigated the early risk of developing cancer by inhalation of low doses (60 µL/day) of methyl tertiary butyl ether (MTBE) vapors using protein SDS-PAGE and LC-MS/MS analysis of rat sera. Furthermore, histological alterations were assessed in the trachea and lungs of 60 adult male Wistar rats. SDS-PAGE of blood sera showed three protein bands corresponding to 29, 28, and 21 kDa. Mass spectroscopy was used to identify these three bands. The upper and middle protein bands showed homology to carbonic anhydrase 2 (CA II), whereas the lower protein band showed homology with peroxiredoxin 2. We found that exposure to MTBE resulted in histopathological alterations in the trachea and the lungs. The histological anomalies of trachea and lung showed that the lumen of trachea, bronchi, and air alveoli packed with free and necrotic epithelial cells (epithelialization). The tracheal lamina propria of lung demonstrated aggregation of lymphoid cells, lymphoid hyperplasia, hemorrhage, adenomas, fibroid degeneration, steatosis, foam cells, severe inflammatory cells with monocytic infiltration, edema, hemorrhage. Occluded, congested, and hypertrophied lung arteries in addition, degenerated thyroid follicles, were observed. The hyaline cartilage displayed degeneration, deformation, and abnormal protrusion. In conclusion, our results suggest that inhalation of very low concentrations of the gasoline additive MTBE could induce an increase in protein levels and resulted in histopathological alterations of the trachea and the lungs.

Immune response to Ichthyophthirius multifiliis and role of IgT.

The parasitic ciliate Ichthyophthirius multifiliis causes white spot disease in freshwater fish worldwide. The theront penetrates external surfaces of the naïve fish where it develops into the feeding trophont stage and elicits a protective immune response both at the affected site as well as at the systemic level. The present work compiles data and presents an overall model of the protective reactions induced. A wide spectrum of inflammatory reactions are established upon invasion but the specific protection is provided by adaptive factors. Immunoglobulin IgT is involved in protection of surfaces in several fish species and is thereby one of the first adaptive immune molecules reacting with the penetrating theront. IgT producing lymphocytes occur in epithelia, dispersed or associated with lymphoid cell aggregations (skin epidermis, fins, gills, nostrils and buccal cavities) but they are also present in central immune organs such as the head kidney, spleen and liver. When theronts invade immunized fish skin, they are encountered by host factors which opsonize the parasite and may result in complement activation, phagocytosis or cell‐mediated killing. However, antibody (IgT, IgM and IgD) binding to parasite cilia has been suggested to alter parasite behaviour and induce an escape reaction, whereby specific IgT (or other classes of immunoglobulin in fish surfaces) takes a central role in protection against the parasite.

Fevipiprant, a selective prostaglandin D2 receptor 2 antagonist, inhibits human group 2 innate lymphoid cell aggregation and function

Fevipiprant, a selective prostaglandin D2 receptor 2 antagonist, inhibits human group 2 innate lymphoid cell aggregation and function

Isolated aggregates of lymphoid cells in the inner bronchial wall in asthma patients.

Here, we report findings in volunteers with bronchial asthma. Biopsies were obtained from the inner bronchial wall before and a short time again after segmental allergen provocation. In most of the baseline biopsies and in all evaluable biopsies after segmental allergen provocation, the follicular lymphoid tissue was detected by immunohistochemistry in the epithelium of these asthmatic patients. The basic occurrence of the tertiary lymphoid tissue in the bronchial mucosa of mild asthmatics was unexpected and may have consequences for the interpretation of pathophysiology, e.g., as a cause or consequence of bronchial asthma.

Identification of Nodular Gastritis among Patients Diagnosed with Lymphofollicular Gastritis on a Gastric Biopsied Specimen

Nodular gastritis (NG) is a well-known endoscopic finding observed in patients with a Helicobacter pylori infection, which may lead to invasive gastric cancer. Lymphofollicular gastritis consists of lymphoid follicles or lymphoid cell aggregates, and is common in children. The aim of this study was to identify patients with NG from those in whom gastric biopsied specimens showed lymphoid follicles and lymphoid cell aggregates. Subjects, whose gastric biopsy specimens showed lymphoid follicles or lymphoid cell aggregates, were included in this study. The inclusion criterion was that they underwent a serum pepsinogen assay on the day of upper gastrointestinal endoscopy. NG was diagnosed if the endoscopy findings revealed regular-sized, multiple, colorless subepithelial nodules. Among 108 subjects who showed lymphoid follicles or lymphoid cell aggregates, 13 (12.0%) revealed NG on endoscopy, and all these subjects showed positive Giemsa staining. Patients diagnosed with NG were younger (p=0.012) and showed a female predominance (p=0.001) compared to those without NG. The mean serum pepsinogen levels were higher (p=0.001) and lymphoid follicle-dominant subjects were more common (p<0.001) in the NG subjects than in those without NG. Logistic regression analysis revealed a younger age (p=0.041) and female gender (p=0.002) to be significant independent risk factors for NG. NG should be distinguished from lymphofollicular gastritis because only 12% of patients showing gastric biopsy findings of lymphoid follicles and lymphoid cell aggregates demonstrated NG on endoscopy. NG is an endoscopic finding that is more common in women and in the younger population, irrespective of the biopsy findings and gastric secretory ability.

A Case of Primary Cutaneous Aggressive Epidermotropic CD8+ Cytotoxic T-Cell Lymphoma

Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma is an aggressively proliferating cutaneous lymphoma expressing CD8+ cytotoxic phenotype. A 61-year-old man presented with a 1-year history of extensively diffuse erythematous plaques on the trunk, upper extremities, and face which had central necrosis with oozing and crust formation. Histopathologic examination displayed diffuse aggregates of atypical lymphoid cells with a pagetoid spreading of epidermotropism. The proliferating lymphocytes indicated strong labelling with CD3, CD8, and were negative for CD4, CD20 and CD56. Molecular analysis exhibited monoclonal rearrangement of TCR genes. Based on these clinical and histologic profiles, the patient was finally diagnosed with primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. This disease, classified as a provisional entity belonging to cutaneous T-cell lymphoma, has been reported in less than 60 case reports. Herein, we described the first Korean case of primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma, characterized by distinct clinicopathological and hard-to-cure features.

The spread of EBV to ectopic lymphoid aggregates may be the final common pathway in the pathogenesis of ME/CFS

According to the hypothesis presented here, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) develops over 3 steps: Step 1 is characterized by the aggregation of lymphoid cells in dorsal root ganglia or other nervous structures. The cause of this formation of ectopic lymphoid aggregates may be an acute infection, asymptomatic reactivations of a common neurotropic virus, exposure to a neurotoxin, or physical injury to peripheral nerves. In step 2, Epstein-Barr virus (EBV)-infected lymphocytes or monocytes bring EBV from the circulation to one or several of these lymphoid aggregates, whereupon cell-to-cell transmission of EBV and proliferation of latently EBV-infected lymphocytes lead to the presence of many EBV-infected cells in the lymphoid aggregates. The EBV-infected cells in the aggregates ignite an inflammation in the surrounding nervous tissue. This local inflammation elicits, in turn, a wave of glial cell activation that spreads from the EBV-infected area to parts of the nervous system that are not EBV-infected, disturbing the neuron-glial interaction in both the peripheral – and central nervous system. In step 3, immune cell exhaustion contributes to a consolidation of the pathological processes. There might be a cure: Infusions of autologous EBV-specific T-lymphocytes can perhaps remove the EBV-infected cells from the nervous system.

Distribution of Podoplanin in Synovial Tissues in Rheumatoid Arthritis Patients Using Biologic or Conventional Disease-Modifying Anti-Rheumatic Drugs.

Podoplanin (PDPN) mediates tumor cell migration and invasion, which phenomena might also play a role in severe rheumatoid arthritis (RA). Therefore, the precise cellular distribution of PDPN and it's relationships with inflammation was studied in RA treated with biologic disease-modifying anti-rheumatic drugs (DMARD) or conventional DMARDs (cDMARD). PDPN+ cells were immunostained by NZ-1 mAb, and scored (3+; >50%/ area, 2+; 20%- 50%, 1+; 5%-20%, 0: <5%) in synovial tissues from RA treated with biologic DMARDs (BIO, n=20) or cDMARD (n=20) for comparison with osteoarthritis (OA, n=5), followed by cell grading of inflammation and cell-typing. Inflammatory synovitis score was 1.4 in both BIO and cDMARD, compared to only 0.2 in OA. PDPN+ cells were found in the lining layer (BIO 1.6, cDMARD 1.3, OA 0.2) and lymphoid aggregates (BIO 0.6, cDMRD 0.7, OA 0.2), and correlated with RA-inflammation in BIO- and cDMARD-groups in both area (r=0.7/0.9, r=0.6/0.7, respectively p<0.05). PDPN was expressed in CD68+ type A macrophage-like and 5B5+ type B fibroblast-like cells in the lining layer, and in IL- 17+ cells in lymphoid aggregates in RA. PDPN was markedly increased in the immunologically inflamed RA synovitis, which was surgically treated due to BIO- and cDMARD-resistant RA. PDPN may have potential of a new marker of residual arthritis in local joints for inflammation-associated severe RA.

Occurrence of lymphoid leukosis in poultry population of Mizoram

A study were undertaken to survey the prevalence of viral diseases of Poultry in Mizoram during March, 2013 to February, 2014. Out of 476 poultry carcasses examined, 208 (43.69%) cases were diagnosed as viral diseases. Among the viral diseases, 28 (5.88%) cases of lymphoid leukosis were recorded based on clinical history, gross and microscopic changes. The disease was found to occur in adult birds above 12 weeks of age with percent morbidity and mortality of 2–3% and 1.5–2.4%, respectively. The characteristic signs recorded during the study included weakness, diarrhea, dehydration, emaciation, anorexia, pale wattle and enlargement of the abdomen. The significant gross lesions were severe emaciation and dehydrated carcasses, markedly enlarged liver and spleen. Microscopically, liver, spleen and other visceral organs revealed aggregates of large lymphoid cells (lymphoblasts) of variable sizes. Confirmatory diagnosis was done based on characteristic microscopic changes in the affected organs.

Tráfico leucocitario y trastorno inflamatorio

IntroductionImmune cells patrol the organism looking for danger signals and pathogens which stimulate mediator production and leucocyte extravasation. Starting of the local inflammatory response (IR)Infected cells and sentinel cells start the IR. Endothelium it is activated and liquids, molecules and leucocytes extravasate. Propagation of the IRLiquids molecules and cells drain from the focus of infection propagating the RI to the secondary lymphoid organs (SLO) where the dendritic cells will present the antigens (Ag) to the T lymphocytes, and the Ag-complement complexes will stimulate the B lymphocytes. Systemic repercussion of the IREfferent lymph carries inflammatory mediators to blood circulation where they will start the acute phase response in the spleen, liver and bone marrow. Adaptive responseIn the SLO, Ag-specific lymphocytes will start the clonal response against the pathogen-Ag and will differentiate in effector and memory cells. Effector cells return to blood and the infected tissues where they eliminate the pathogen. They can form structured aggregates of lymphoid cells (granulomas and the ectopic lymphoid follicles). Clinical responseThe increased production of soluble mediators of the IR can cause pathologies. These mediators of leucocyte extravasation are putative therapeutic targets for the control of the IR.

Extra-Adrenal Myelolipoma Containing Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia: A Case Report and Review of the Literature.

Myelolipoma is a benign tumor consisting of mature fat interspersed with hematopoietic elements resembling bone marrow. The vast majority occurs within the adrenal glands, but several cases of extra-adrenal myelolipomas (EAMLs) have been reported. We report a case of a 64-year-old male who presented with complaint of lower abdominal discomfort. CT scan of abdomen and pelvis showed a 6 cm × 5 cm, well-circumscribed, predominantly fatty mass in the presacral region. Histological examination of the pelvic mass revealed a myelolipoma heavily infiltrated by small lymphoid cell aggregates with immunophenotypic features of small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). Review of the literature revealed that there is only one published report of SLL/CLL involving a myelolipoma, which was also an extra-adrenal myelolipoma, and, therefore, our case is the second case of a SLL/CLL involving a myelolipoma that is an extra-adrenal myelolipoma. Extra-adrenal myelolipomas seem to the preferred myelolipomas for involvement by SLL/CLL.

Abstract 1550: Significance of ectopic lymph node-like structures in neuroendocrine tumors of the small bowel

Abstract The formation of extranodal tertiary lymphoid follicles and lymphoid cell aggregates has been described in nonmalignant conditions including autoimmune diseases and chronic inflammation as well as in cancer. Tumor-induced lymph node-like structures (LLS) participate in the host's antitumor immune response by driving intratumoral immune cell priming. We evaluated the host immune response by immunohistochemistry in 60 well differentiated small bowel NETs. A miRNA microarray analysis was also performed to identify a molecular signature of LLS presence. In 13/60 samples the immune response was organized as ectopic LLS. When present, LLS were localized at the invasive edge of the tumors and contained germinal centers in different stages of maturation. CD21+ dendritic cells were present within the follicular germinal centers, while CD3+ T cells were dispersed in the parafollicular cortex zone surrounding the CD20+ B cell area of the follicles. Time to progression of metastatic tumors was compared in an exploratory cohort of 5 patients with strong evidence of LLS vs 5 patients with no evidence of LLS and was substantially longer in the former group (94 vs 28 months; p = 0.15). Updated survival and miRNA microarray analysis will be presented at the meeting.The understanding of the functional nature of LLS may provide new insights into the pathogenesis of the disease, possibly furnishing a new tool for prognostic stratification and prediction of response to immune-based treatments. Citation Format: Mauro Cives, Jonathan Strosberg, Stacey A. Simons, Domenico Coppola. Significance of ectopic lymph node-like structures in neuroendocrine tumors of the small bowel. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1550. doi:10.1158/1538-7445.AM2015-1550