Proliferation Of Lymphoid Tissue Research Articles

Orbital Lymphoma on a Case in a Secondary Center in Sikasso

Malignant lymphomas constitute a very heterogeneous group of malignant proliferation of lymphoid tissue whose starting point is extramedullary. The confirmatory diagnosis is based on the anatomopathologic examination of the surgical specimen. Immunohistochemical typing is used to determine Hodgkin's Lymphoma (HL) and other non-Hodgkin's lymphomas (NHL). The treatment of these lymphomas involves a multidisciplinary approach and includes surgical excision, cryotherapy, chemotherapy which can be associated with radiotherapy. Very few studies carried out on orbital lymphomas in Sikasso. The purpose of our study was to write the diagnostic procedures in a secondary center and the management as well as the prognosis. It was a 23-year-old young woman with no particular history, no notion of taking stimulants, who consulted for a necrotizing and painful swelling of the right eye evolving for more than 1 year in a progressive manner despite corticosteroid therapy. Imaging and pathological examination of the surgical specimen led to the diagnosis of large cell lymphoma. Surgical excision was the therapeutic means performed. The postoperative course was good with healing of the wound after 2 months. After 3 months of follow-up, the patient would have died after a period of loss of sight. The clinical polymorphism of lymphomas can mask the diagnosis and delay the therapeutic management which determines the prognosis.

Targeting neuropilin-1 abolishes anti-PD-1-upregulated regulatory T cells and synergizes with 4-1BB agonist for liver cancer treatment.

Regulatory T cells (Tregs) are an obstacle to PD-1 blockade-mediated antitumor efficacy. However, the behaviors of Tregs response to anti-PD-1 in HCC and the characteristics of Tregs tissue adaptation from peripheral lymphoid tissues to the tumor are still unclear. Here, we determine that PD-1 monotherapy potentially augments the accumulation of tumor CD4 + Tregs. Mechanistically, anti-PD-1 mediates Tregs proliferation in lymphoid tissues rather than in the tumor. Increased peripheral Tregs burden replenishes intratumoral Tregs, raising the ratio of intratumoral CD4 + Tregs to CD8 + T cells. Subsequently, single-cell transcriptomics revealed that neuropilin-1 (Nrp-1) supports Tregs migration behavior, and the genes of Crem and Tnfrsf9 regulate the behaviors of the terminal suppressive Tregs. Nrp-1 + 4-1BB - Tregs stepwise develop to the Nrp-1 - 4-1BB + Tregs from lymphoid tissues into the tumor. Moreover, Treg-restricted Nrp1 depletion abolishes anti-PD-1-upregulated intratumoral Tregs burden and synergizes with the 4-1BB agonist to enhance the antitumor response. Finally, a combination of the Nrp-1 inhibitor and the 4-1BB agonist in humanized HCC models showed a favorable and safe outcome and evoked the antitumor effect of the PD-1 blockade. Our findings elucidate the potential mechanism of anti-PD-1-mediated intratumoral Tregs accumulation in HCC and uncover the tissue adaptation characteristics of Tregs and identify the therapeutic potential of targeting Nrp-1 and 4-1BB for reprogramming the HCC microenvironment.

Histopathological Features of Helicobacter pylori Infection in Gastric Mucosa.

To investigate the histopathological characteristics of Helicobacter pylori (Hp) infection in the gastric mucosa in the process from occurrence to intraepithelial neoplasia. Specimens obtained from the endoscopic biopsy and endoscopic submucosal dissection of 2457 cases of gastric Hp infection were observed and assessed in detail using histology and immunohistochemistry techniques. The condition was divided according to the histopathological characteristics of gastric mucosal damage caused by Hp infection. The histopathological characteristics and immunophenotype of each stage were subsequently elucidated. Helicobacter pylori is initially implanted in the mucus layer covered by the epithelium on the surface of the gastric mucosa. It then selectively adheres to the cytoplasm of the surface mucus cells, which makes the oval and spherical particles containing mucus that is wrapped by the bounded membrane in the cytoplasm on the nucleus of the surface mucus cells disappear, while the cytoplasm undergoes spiderweb-like vacuolar degeneration. This leads to the proliferation and transformation of the surface mucous cells before developing into intraepithelial neoplasia. In the process of histomorphology, mucosal ulcers, mucosal lymphoid tissue proliferation, gland atrophy, intestinal epithelial metaplasia, mucosa-associated lymphoid tissue lymphoma, and adenocarcinoma may occur. In this study, the condition was divided into five stages according to the histopathological characteristics of gastric mucosal damage caused by Hp infection, as well as the degree of gastric mucosal damage and involvement depth as follows: the mucus infection stage, the surface epithelial cell infection stage, the lamina propria lesion stage, the mucosal atrophy stage, and the intraepithelial neoplasia stage. Understanding the histopathological characteristics of gastric Hp infection in terms of its occurrence and development into intraepithelial neoplasia is conducive to the precise treatment and tracking of malignant cell transformation, and is of great significance in controlling the occurrence and development of gastric cancer.

Benign lymphoid hyperplasia of tongue base compromising the airway

AbstractBackgroundBenign lymphoid hyperplasia (BLH) is a benign proliferation of lymphoid tissue in response to external irritation. Although it had been described in the literature, occurrence within oral cavity is rare.MethodsWe reported a severe case of tongue base BLH compromising the breathing and swallowing of the affected patient. Clinically it mimicked a neoplastic lesion.ResultsThe patient was successfully treated by tracheostomy, debulking excision and a course of postoperative steroid. The diagnosis was confirmed on histopathology examination. There is no disease recurrence after a follow‐up of 11 months.ConclusionsBLH of tongue base can masquerade as malignancy and rarely compromise the upper airway. Prompt reduction surgery plus postoperative steroid can affirm the diagnosis and cure the disease.

Pulmonary lymphoproliferative disorders in children: a practical review.

Pulmonary lymphoproliferative disorders represent an uncommon spectrum of proliferation of lymphoid tissue in the lung parenchyma ranging from benign hyperplasia to malignancy. They tend to occur in certain clinical situations and have typical imaging features that together can be used by the radiologist to suggest these entities as part of the differential diagnosis. We review key clinical, histopathological and computed tomography features of pulmonary lymphoproliferative disorders in children including follicular bronchiolitis, lymphoid interstitial pneumonia, granulomatous-lymphocytic interstitial lung disease, lymphoma and post-transplant lymphoproliferative disorder to familiarize the pediatric radiologist with this group of disorders.

The clinicopathologic features and differential diagnosis of ocular Kimura disease and epithelioid hemangioma

Objective: To investigate the clinicopathologic features and differential diagnosis of ocular Kimura disease (KD) and epithelioid hemangioma. Methods: It was a retrospective case series study. The data of 10 patients with ocular KD and 3 patients with ocular epithelioid hemangioma from the Pathology Department of Eye & ENT Hospital of Fudan University from January 2010 to December 2019 were retrospectively analyzed, including clinical manifestations, morphology and immunophenotypes. Results: Among patients with ocular KD, there were 9 males and 1 female with an age from 7 to 75 years (mean, 30 years). There were 6 unilateral cases and 4 bilateral cases. The disease mainly involved the orbit in 3 patients, the lacrimal gland in 5 patients and the eyelid in 2 patients. The ophthalmic presentation included a palpable periorbital or eyelid mass with eyelid swelling and ptosis, proptosis and displacement of the eyeball, and ocular dysmotility. Three patients had a history of lymphadenopathy. The disease course ranged from 6 months to 7 years (mean, 34 months). All the patients had elevated peripheral blood eosinophilia. Three patients of ocular epithelioid hemangioma were all males with age from 25 to 60 years old. They were all unilateral cases with 1 right eye and 2 left eyes. The disease respectively involved eyelid and orbit, the eyebrow skin and the inner canthus skin. They presented with eyelid swelling, orbital mass or subcutaneous nodule for 5 months to 2 years. All patients (11 eyes) with KD underwent incisional or excisional biopsy. The histopathology revealed follicular hyperplasia of lymphoid tissue with active germinal centers in orbital fibroadipose tissue. There were massive interfollicular eosinophils with eosinophilic microabscesses. Some swelling endothelial cells of proliferating vessels were seen. All the 3 patients (3 eyes) with ocular epithelioid hemangioma underwent excision of the lesions. Histopathological examination showed proliferation of small and medium blood vessels. The vessels were lined by endothelial cells with abundant eosinophilic cytoplasm which protruded into the lumen. The endothelial cells were positive for CD31, factor Ⅷ-related antigen and E26 transformation-specific related gene immunohistochemically. There was a moderate amount of lymphocytes, plasma cells and eosinophils surrounding blood vessels without eosinophilic microabscess. Conclusions: Both ocular KD and epithelioid hemangioma are more commonly seen in males and share the common histopathological features of vascular proliferation, swelling endothelial cells and eosinophilic infiltration. KD is an allergic benign lymphoid tissue proliferation characteristic of massive eosinophilic infiltration, whereas epithelioid hemangioma is a benign neoplasm of blood vessels with plump and epithelioid endothelial cells. (Chin J Ophthalmol, 2021, 57: 689-695).

Celecoxib ameliorates liver cirrhosis via reducing inflammation and oxidative stress along spleen-liver axis in rats

Background & aimsSplenomegaly is usually taken as a consequence of liver cirrhosis. However, as a risk factor for cirrhosis, the impacts of spleen-liver axis on the development of cirrhosis are largely unknown. This study focused on the impacts of splenomegaly on the development of cirrhosis and assessment of the effects of celecoxib, a selective COX-2 inhibitor, on the splenomegaly and cirrhotic liver. Materials and methodsLiver cirrhosis was induced by thioacetamide (TAA). Sixty rats were randomly divided into control, TAA-16w, TAA + celecoxib groups and normal, TAA + sham, TAA + splenectomy groups. Hepatic stellate cells (HSCs) or hepatocytes were co-cultured with splenocytes from those groups. ResultsSplenocytes of cirrhotic rats stimulated the HSCs activation and induced hepatocyte apoptosis via enhancing oxidative stress. The hepatic levels of NOX-4 and the in situ O2− were profoundly reduced in TAA + splenectomy group by 50.6% and 18.5% respectively, p < 0.05. Celecoxib significantly decreased the hepatic fibrotic septa induced with TAA by 50.8%, p < 0.05. Splenic lymphoid tissue proliferation and proinflammatory cytokines of the cirrhotic rats were also obviously suppressed by celecoxib, p < 0.05. Compared with the HSC or hepatocyte cell line co-cultured with the cirrhotic splenocytes, the expression of alpha-SMA, NOX-4, in situ O2− or the levels of cleaved caspase3 and NOX-4 were significantly decreased in those cell lines co-cultured with cirrhotic splenocytes treated by celecoxib, p < 0.05. ConclusionSplenomegaly contributed to the development of liver cirrhosis through enhancing oxidative stress in liver. Celecoxib could effectively ameliorate liver cirrhosis via reducing inflammatory cytokines and immune cells derived from spleen and suppressing oxidative stress.

Importance of Flow Cytometry in the Immunophenotyping Characterization of Mantle Cell Lymphoma in State of Rio Grande Do Norte, Brazil

Introduction:Mantle Cell Lymphoma (MCL) is a disease of a neoplastic nature characterized by proliferation in lymphoid tissues, classified as non-Hodgkin's lymphoma of B lymphocytes (NHBL). The nomenclature derives from the specific pathophysiology of this disease, that proliferates in the marginal area of the mantle of the germinal center of the lymph nodes.Objective:Carry out a detailed assessment of the immunophenotypic profile using the flow cytometry (CF) technique in 26 patients, NHBL to confirm mantle lymphoma.Materials and Methods:Biological samples from 26 patients, these being from peripheral blood (SP) or bone marrow (MO), of patients with suspected MCL were marked with monoclonal antibodies conjugated to fluorochromes and subsequently analyzed by FC.Results:all patients with a confirmed diagnosis of LCM were positive for pan-B antigens CD19, CD20 (strong) and CD22 (strong), CD19+/CD5+ and ciclin-D1 in 100% of cases. In addition to these, CD23, CD56, CD38, CD79b, Ki-67, Bcl-2, FMC-7 and HLA-Dr also obtained positive staining, as well as the immunoglobulin heavy chain (IgH) in all cases, and isotypes of immunoglobulins, IgD, IgG and IgM in most cases, with a predominance of the heavy chain of the lambda light chain in 79% of cases. Antigens related to T lymphocytes such as CD1a, CD2, CD3, CD7, TCR alpha/beta, TCR gamma/delta, CD4 and CD8, as well as antigens related to NK cells (CD16-56) and lymphoid progenitor cells (CD10 and Terminal- deoxynucleotidyl-transferase) were negative, as were CD200, antigens related to hairy cell leukemia (CD103, CD11c and CD123) and multiple myeloma (CD138).Discussion:According to the expression of the antigens, the antibodies were positive for: Cyclin D, CD19, CD20, CD22, CD38, Ki-67, Bcl-2, FMC-7 and CD79b, which are relevant to the diagnosis of this disease. Conclusion: Flow cytometry immunophenotyping is the technique currently used to confirm the diagnosis of neoplasms, such as LCM, which, due to its specific phenotype, helps in the correct selection of treatment. Disclosures No relevant conflicts of interest to declare.

The Effectiveness of Laboratory Methods for the Early Differential Diagnosis of Ophthalmohlamidiosis and Conjunctival Lymphoma (Clinical Cases)

Conjunctival lymphomas are predominantly extranodal B-cell non-Hodgkin’s lymphomas (NHL), most of them are MALT-lymphomas originating from the mucosa-associated lymphoid tissue. Manifestations of the conjunctival NHL are very diverse, and often imitate the appearance of other ocular diseases, which makes their clinical diagnosis difficult and significantly lengthens the time from the first visit to the ophthalmologist until the diagnosis is verified. The article presents the case histories of two young patients who were treated for a long time at the place of residence as acute chlamydial conjunctivitis (in one case — 3, in the other — almost 5 months). A comprehensive laboratory study to detect specific blood antibodies, DNA of the pathogen in conjunctival scrapings and the cytological picture of the conjunctiva did not confirm the chlamydial etiology of the process. A pronounced lymphoid reaction mainly due to small lymphoid cells was found in both patients in scrapings from the conjunctiva of the eyelid, which was the basis for referring patients for consultation to oncologist. Histological examination of conjunctival biopsy specimens also revealed proliferation of lymphoid tissue: patients with suspected MALT lymphoma were referred to onco-hematologists. A PCR analysis of the biopsy material revealed HHV-8 DNA in one patient and Epstein-Barr (EBV) DNA in another, although no pathogen genomes were detected in the conjunctiva scrapings. Immunohistochemical analysis in one patient confirmed the conjunctival MALT-lymphoma, in another one diagnosed hyperplasia of the conjunctival mucous-associated lymphoid tissue, caused by prolonged antigenic stimulation (EBV DNA was detected in the biopsy). The follicular appearance of the lymphocyte hyperplasia in conjunctiva may imitate the clinical picture of infectious diseases. For differential diagnosis of chlamydial conjunctivitis and MALTlymphoma, especially in young patients with refractory follicular conjunctivitis, it is advisable to include a set of serological, molecular biology and cytological methods.

Castleman Hastalığı: Laparoskopik yaklaşımla tedavi edilen pararenal alanda nadir bir retroperitoneal kitle

Unicentric Castleman’s Disease (UCD) is a rare disorder with unknown etiology. UCD is characterized by a localized lymphoid tissue proliferation and interfollicular hypervascularity. It is a rarely seen mass in the pararenal space, which can mimic other tumors. In this case, we present a retroperitoneal UCD which is treated with laparoscopic approach in our clinic

Post-transplantation lymphoproliferative disorders: Current concepts and future therapeutic approaches.

Transplant recipients are vulnerable to a higher risk of malignancy after solid organ transplantation and allogeneic hematopoietic stem-cell transplant. Post-transplant lymphoproliferative disorders (PTLD) include a wide spectrum of diseases ranging from benign proliferation of lymphoid tissues to frank malignancy with aggressive behavior. Two main risk factors of PTLD are: Firstly, the cumulative immunosuppressive burden, and secondly, the oncogenic impact of the Epstein-Barr virus. The latter is a key pathognomonic driver of PTLD evolution. Over the last two decades, a considerable progress has been made in diagnosis and therapy of PTLD. The treatment of PTLD includes reduction of immunosuppression, rituximab therapy, either isolated or in combination with other chemotherapeutic agents, adoptive therapy, surgical intervention, antiviral therapy and radiotherapy. In this review we shall discuss the prevalence, clinical clues, prophylactic measures as well as the current and future therapeutic strategies of this devastating disorder.

Castleman’s disease associated with mixed connective tissue disorder and cerebral ischaemia and vasculitis: A rare case and a diagnostic challenge for an infectologist

Introduction. Castleman's disease (CD) or angiofolicullar lymph node hyperplasia is a rare pathologic process characterized by non-neoplastic reactive proliferation of lymphoid tissue. Mimicking clinical and laboratory signs of infection, it could be a great diagnostic problem for an infectologist. Case report. We report a case of a 39-year old man who was initially clinically suspected to have an infectious central nervous system (CNS) affection, having most similar appearance to neurotuberculosis. Malignancy with bone metastases and lymphoma were also among many possible diagnoses. The patient was later histologically confirmed to have Castleman's disease, analyzing the enlarged inguinal lymph node, which was the key point in rejecting the suspicion of malignancy and tuberculosis. By further analyses, the patient was diagnosed to have mixed connective tissue disorder (MCTD). Vasculitis of mesencephalon and thalamus was detected by magnetic resonance imaging. Conclusion. CD with CNS involvement is very rare as well as CD with MCTD association, making this case even more unique. This case report underlines the importance of definitive histological diagnosis in patients with lymphadenopathia associated with systemic involvement and the need of additional immunological and radiological examinations, as well.

Laparoscopically resected Castleman's disease in the pelvic retroperitoneum: A case report.

Castleman's disease is a rare benign disorder of unknown etiology characterized by proliferation of lymphoid tissues. Castleman's disease arising from pelvic retroperitoneum is clinically rare. The present case report describes a rare case of laparoscopically resected Castleman's disease in the pelvic retroperitoneum associated with benign ovarian cyst. A 47-year-old woman, gravida 5, para 3, was referred to to the Department of Obstetrics and Gynecology of Wakayama Medical University with a suspected pelvic tumor. Magnetic resonance imaging revealed that the solid tumor was localized in the retroperitoneal space at the right side of the pelvis. The patient underwent laparoscopic surgery for the resection of the pelvic retroperitoneal tumor, with complete tumor resection. Postoperative pathological examination established the diagnosis of Castleman's disease. The postoperative course was uneventful, with no evidence of local recurrence or systemic disease 6 months after diagnosis.

2669 Mucosa-Associated Lymphoid Tissue Lymphoma: Crossing the Borders!

INTRODUCTION: Mucosa-associated lymphoid tissue (MALT) lymphoma or MALTomas are responsible for half of the primary gastric lymphomas and up to 8% of B-cell lymphomas. It mostly affects patients in their 5th or 6th decade of life. MALT lymphoma is well known to remain localized in the stomach and to follow a benign course. Despite that gastric MALToma is well defined in the literature, it is rather uncommon to present as a peri-pancreatic mass. Herein, we present the case of a patient with an incidental peri-pancreatic mass diagnosed as an aggressive form of MALT lymphoma. CASE DESCRIPTION/METHODS: A 76-year-old male with hypertension presented to the gastroenterology clinic for the evaluation of peri-pancreatic mass incidentally found during computed tomography (CT) scan performed for renal colic. Physical examination was remarkable for an epigastric fullness with no tenderness. Laboratory tests were remarkable for iron deficiency anemia. CT showed a 7 cm ill-defined soft tissue mass within the pancreaticoduodenal groove abutting the pancreatic head and encasing the gastroduodenal artery suspicious for a pancreatic neoplasm (Figure 1). Endoscopic ultrasound (EUS) showed a hypoechoic heterogeneous mass arising from the gastric wall in close proximity to the pancreas (Figure 2). EUS-guided biopsies were consistent with extra-nodal marginal zone lymphoma of MALT (Figure 3). Gastric biopsies confirmed the presence of MALToma and revealed positive Helicobacter Pylori (HP) infection. Staging workup confirmed extensive bone marrow as well as para-aortic, mediastinal and paratracheal lymph node involvement. The patient received curative HP treatment and was started on bendamustine and rituximab. DISCUSSION: The stomach is the most commonly affected organ by MALT lymphoma. Helicobacter Pylori is a major precursor for the development of gastric MALT lymphoma as up to 90% of affected patients show H.Pylori on stomach biopsies. Chronic HP infection leads to lymphoid tissue proliferation within the stomach and progression towards lymphoma. In this setting, the course is usually indolent with the disease usually confined to the stomach but aggressive tumor behavior has been reported. HP antibiotic eradication remains the first line therapy for early-stage HP positive gastric MALT lymphoma. In other instances, a patient-tailored approach is recommended based on the stage, involved site, HP status and clinical characteristics. Therapeutic options include radiation therapy, chemotherapy and surgery accordingly.

Clinical and epidemiological features of infections caused by HHV-6A and HHV-6B

Objective. To determine the detection rates of HHV-6A and HHV-6B compared to other herpes viruses in children of different age groups. Materials and Methods. A total of 128 patients with symptoms of respiratory viral infections (RVI) aged from 1 to 16 years and 101 otherwise healthy children. A comprehensive examination of the patients, including ELISA, indirect immunofluorescence assay, rapid culture method, PCR, and determination of nucleotide sequences of HHV-6 was performed. Children positive for HHV-6 markers (antibodies, early and late antigens) and positive for HHV-6 DNA were selected into one group (n=59), of which 14 children aged from 3 to 10 years were healthy and 45 children (&lt;3 years of age [20 children] and ≥3 years of age [25 children]) had clinical manifestations of RVI. Results. The incidence rates of acute HHV-6 infection and HHV-6 reactivation were similar between healthy children and children with RVI symptoms (21.9% each). The active Epstein-Barr Virus (EBV) infection took a second place among examined children: acute EBV infection and EBV reactivation were determined in 19 (14.8%) and 10 (7.8%) children, respectively. The incidence rates of HHV-6A and HHV6B among children with RVI symptoms were similar (55.5% and 42.2%, respectively) whereas HHV-6B was predominant in healthy children (85.7%). The HHV-6A was more common (70%) in children under 3 years of age, but HHV-6B was more frequent (67%) in children aged 3 years and older. The most often initial manifestations of HHV-6A infection were acute fever and catarrhal syndrome; whereas HHV-6B was found more frequently in otherwise healthy children. A sudden exanthema and febrile seizures were significantly more common symptoms in children with HHV-6A infection, whereas tonsillar enlargement with exudate and swollen lymph nodes were observed more frequently in children with HHV-6B infection. Conclusions. HHV-6A more often causes acute infection in children less than 3 years of age, which is characterized by fever, febrile seizures, rash (roseola), and upper respiratory tract infection with significant catarrhal syndrome. HHV-6B more often causes acute infection in children aged 3 years and older and is rarely presented with specific symptoms of HHV-6 infection, such as sudden exanthema and febrile seizures. HHV-6B is characterized by lymphoid tissue proliferation (tonsillar enlargement and lymphadenopathy) and hepatomegaly in all age groups of children.

Unicentric hyaline vascular type of castleman disease of the renal hilum with diagnostic dilemma: A case report and review of literature

Castleman disease (CD) represents a morphologically distinct variety of benign proliferation of lymphoid tissue. Renal hilum involvement is rare and may be confused with renal malignancy or granulomatous diseases. Here, we report a rare case of unicentric CD of renal hilum. A 56-year-old male patient presented with flank pain and voiding symptoms. Contrast-enhanced computed tomography scan showed a left renal hilar tumor mimicking a renal malignancy which led to nephrectomy. Our case is the first report of the unicentric hyaline vascular type of CD of the renal hilum reported from India. Awareness of such cases is important for radiologists and surgeons to prevent the misdiagnosis of a renal malignant tumor and to avoid nephrectomy.

A Rectal Tonsil Like No Other

Rectal tonsil is a rare condition. Its etiology is unknown, but it is comprised of a reactive proliferation of lymphoid tissue. Here we present a case of large, bleeding rectal tonsil. A 33-year-old healthy female presented with a 3-year history of intermittent rectal bleeding. Initial colonoscopy revealed irregular granular-appearing rectal mucosa, which was partially circumferential and extended 10 cm from the anal verge. Biopsy showed atypical lymphoid infiltrate positive for CD-20 and bcl-2, concerning for low-grade B-cell non-Hodgkin lymphoma. Endoscopic ultrasound showed mild, diffuse wall thickening of the mucosal/submucosal layer. Biopsies confirmed reactive lymphoid hyperplasia with flow cytometry negative for clonal population. She continued to have rectal bleeding at 6-month follow-up. Repeat colonoscopy showed a circumferential area of severely granular mucosa from the dentate line to 5 cm from the anal verge. Biopsies again revealed reactive lymphoid hyperplasia with negative flow cytometry and FISH. Currently, the patient continues to be monitored with close follow-up. The rectal tonsil is a rare finding. The most common presentation is rectal bleeding. Our case is the largest lesion presented in the literature as majority of the lesions reported consisted of discrete small (< 6mm) polypoid lesions or nodules. Previous studies reported complete resection of these small discrete lesions and show no recurrence or lymphoma transformation. However, the follow up for these studies is brief. Rectal tonsil should be distinguished from MALT lymphoma and other lymphoid diseases with malignant potential. Our patient is unique as the lesion was large and circumferential; therefore the patient elected to remain under close surveillance. It is important to continue to surveillance of these patients to understand long-term outcomes.Figure: Colonoscopy: Rectal tonsil.Figure: Colonoscopy: Rectal tonsil (retroflexion).

Abstract 1637: ICOS agonism induces potent immune activation and anti-tumor response in non-clinical models

Abstract Inducible T-cell costimulator (ICOS) is a costimulatory receptor that is upregulated on activated CD4 and CD8 T cells and plays an important role in T cell survival, differentiation, regulation of memory and regulatory T cell pools and humoral responses. Preclinically, augmenting signaling through the ICOS pathway has been reported to induce anti-tumor activity and enhance responses to CTLA4 blockade. Here we present non-clinical data evaluating ICOS agonist antibody activity in human and mouse model systems using a different antibody for each species. GSK3359609 is a novel, selective anti-human ICOS agonist. GSK3359609 induces ICOS signaling through phosphorylation of intermediates in the Pi3K pathway leading to lymphocyte activation, proliferation and pro-inflammatory cytokine secretion in human PBMC in-vitro. A robust increase in CD4 effector T cell proliferation and Granzyme B secreting CD8 T cells was observed with GSK3359609 treatment in in-vitro assays utilizing PBMC from healthy donors, cancer patients or tumor infiltrating lymphocytes (TIL). Modest induction of regulatory T cell proliferation and IL-10 secretion were also observed. Significant increase in IFNγ (p&amp;lt;0.05) and TNFα secretion was observed in both primary PBMC and TIL based assays. Gene expression analysis of GSK3359609 treated human T cells confirmed changes in genes associated with T and B cell activation. In mice, an ICOS surrogate antibody was utilized in immune competent mouse tumor models. Tumor regressions were observed in 10-40% of mice and were associated with a robust increase in effector memory T cells in periphery as well as increases in T cell activation and proliferation in lymphoid tissues and tumor. Robust increases in PD1, PD-L1 and PD-L2 gene expression were observed in the tumors from ICOS antibody treated mice along with an increase in cytotoxic T cell signature and induction of an IFNγ gene signature. Changes in regulatory T cell proliferation were also observed in the blood and tumor of mice treated with the mouse ICOS agonist however changes were consistently less in magnitude than corresponding functional changes in cytotoxic CD8+ and effector CD4 cells. We further explored treatment settings where a combination therapy may condition the tumor immune microenvironment to a more favorable context for ICOS agonist therapy. Treatment with an anti-PD1 antibody resulted in strong upregulation of ICOS expression on tumor infiltrating CD8, CD4 effector and regulatory T cells while decreasing ICOS+ Tregs relative to CD8 and CD4 effectors in the tumor microenvironment. Synergistic anti-tumor activity was observed for the combination of PD-1 with ICOS agonist antibodies in preclinical studies. These studies provide a strong rationale for the ongoing FTIH Phase I study of GSK3359609 administered alone and in combination with pembrolizumab to patients with selected advanced solid tumors. Citation Format: Sapna Yadavilli, Tianqian Zhang, Ashleigh Hahn, Laura M. Seestaller-Wehr, Hong Shi, Yao-Bin Liu, M.Phillip DeYoung, David J. Kilian, Meixia Bi, Michael P. Adam, Shu-Yun Zhang, Sabyasachi Bhattacharya, Yuliya Katlinskaya, Christina Blackwell, Christopher B. Hopson, Niranjan Yanamandra, Roopa Srinivasan, Patrick A. Mayes, Axel Hoos. ICOS agonism induces potent immune activation and anti-tumor response in non-clinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1637. doi:10.1158/1538-7445.AM2017-1637

Experimental observation on the histopathological and ultrastructural pathology of Great Gerbils (Rhombomys opimus) in the Junggar Basin by subcutaneous injecting of Yersinia pestis

Objective: To understand the histopathological and ultrastructural pathology changes of great gerbils in the Junggar Basin to Yersinia pestis infection. Methods: Forty captured great gerbils from the Junggar Basin that tested negative for anti-F1 antibodies were infected. The Y. pestis strain 2504, isolated from a live great gerbil in the natural plague foci of the Junggar Basin in 2005 with a median lethal dose (LD(50)) of <10 CFU/ml, was used in this study. Forty great gerbils were divided into seven infection groups and were subcutaneously infected with 7.4×10(5), 7.4×10(6), 7.4×10(7), 7.4×10(8), 7.4×10(9), 7.4×10(10), or 3.0×10(11) CFU/ml of 2504. One milliliter of physiological saline was injected in the noninfected group as a control. We collected the liver, spleen, heart, and lung from all animals for histopathologic and ultrastructural pathology examination. Results: Great gerbils in the 7.4×10(8)-3.0×10(11) CFU/ml groups did not survive and exhibited pathological changes and altered ultrastructural pathology. The liver tissue of infected great gerbils showed spotty necrosis and fatty degeneration, intranuclear canaliculi with increased hepatocytes, and uneven distribution of organelles. Additionally, reactive proliferation of lymphoid tissue in the spleen, blood sinusoid lacunae with neutrophil infiltration, and phagocytosed bacteria in phagocyte cells were observed. Myocardial fiber hypertrophy and interstitial indistinction, nuclear matrices decreased in cardiac myocytes, and loose arrangement of myogenic fibers in myocardial cells were also observed. Angiectasia, capillary congestion, and tissue necrosis were found in the lung. No significant difference in histopathological and ultrastructural pathology in the parenchymal organ was observed between the 7.4×10(5)-7.4×10(7) CFU/ml groups and the 7.4×10(8)-3.0×10(11) CFU/ml groups, and no specific death caused by Y. pestis infection was apparent in the 7.4×10(5)-7.4×10(7) CFU/ml groups. Conclusion:Y. pestis infection altered tissue and ultrastructural pathology in the parenchyma apparatus of great gerbils. In particular, the liver and spleen appeared to be the primary site of Y. pestis infection in great gerbils.

The etiological structure of diseases in frequently ill children depending on age

The urgency of the problem of frequently ill children is associated with a significant number of patients who can be assigned to this category. Objective: to present the nosological and etiological structure of diseases in frequently ill children depending on age. Subjects and methods. 243 children aged 1 to 17 years with recurrent respiratory infections were followed up. The children were examined using routine clinical, laboratory, and instrumental examinations. The etiological diagnosisincluded bacteriological examination of the upperrespiratory tract microflora; determination of IgM and IgG antibodies against Chlamydophila pneumoniae, Mycoplasma pneumoniae, Epstein–Barr virus(EBV), and cytomegalovirus(CMV) in blood by enzyme immunoassay and that of Chlamydia and Mycoplasma DNA in pharyngealswabs and that of CMV, EBV and human herpesvirustype 6 DNA in blood by polymerase chain reaction. Results. Recurrentrespiratory diseases were found to be associated with herpesvirusinfection in 75% of the children aged 1 to 6 years, with Streptococcus, Mycoplasma, and Chlamydia infections in 16, 10, and 4% of those aged 3 to 6 years, respectively, and to be accompanied by abnormal lymphoid tissue proliferation in 84% of the children aged 3 to 6 years, with the abundant growth of bacterial opportunistic pathogensin one half of the patients. Despite the continuing importance of infectious agents(herpesviruses and streptococci in 29 and 20%, respectively), the chronically ill school-aged children displayed a high incidence of somatic diseases: chronic tonsillitis (43%) and chronic sinusitis (14%) in children aged older than 12 years and allergic rhinitis (23%) in those aged 7 to 17 years. The symptoms of autonomic vascular dystonia were observed in 21% of the patients; cardiac arrhythmias were diagnosed in 14%.