Lymphoid Infiltration Research Articles

Oral and maxillofacial manifestations of IgG4-related disease: A clinicopathological study.

IgG4-related disease is a fibroinflammatory and immune-mediated condition, which has extremely variable clinical manifestations. In this study, we aim to investigate the clinicopathological features of IgG4-related disease involving the oral and maxillofacial region. Cases of IgG4-related disease manifesting in the oral and maxillofacial region were retrieved from three Brazilian institutions. Clinical and serological data were obtained from the patients' medical charts, while microscopic and immunohistochemical findings were revised by oral pathologists. Diagnosis followed the American College of Rheumatology/European League against Rheumatism criteria. Seven patients diagnosed with IgG4-related disease were included in this study. Women were affected in all analysed cases, with a mean age of 55.4 years. Two patients presented with the clinical involvement of more than one oral and maxillofacial anatomic site. Therefore, our sample comprised nine oral and maxillofacial anatomic sites affected by IgG4-related disease. The submandibular gland was affected in four cases, the tongue and the parotid gland in two cases each, and the palate in one case. In a few cases, exploratory lower lip biopsy was used as a diagnostic approach. A moderate-to-severe lymphoid infiltrate containing plasma cells and lymphocytes, with an increased IgG4/IgG ratio, was common. Treatment varied and steroids were the most frequently used (57.4%). Six patients remained alive, while one died from unknown causes. Although major salivary glands are commonly affected by IgG4-related disease, the oral cavity can also be involved, and lower lip biopsy may be an auxiliary diagnostic tool.

Achy Breaky Heart: A Case of Lymphocytic Myocarditis Mimicking Takotsubo Cardiomyopathy

<h3>Introduction</h3> Myocarditis is an inflammatory disease of the myocardium that may be due to immune system activation, infection or exposure to toxic substances. The clinical presentation and trajectories encompass a wide spectrum. We present a case of cardiogenic shock fulfilling both the Mayo criteria for myocarditis and the WHO criteria for Takotsubo cardiomyopathy, distinguished by endomyocardial biopsy. <h3>Case Report</h3> A 65-year-old female with a history of mitral valve repair, hypertension and diabetes presented with acute onset chest pain and dyspnea. She denied recent viral illness. Upon examination, she was tachycardic with elevated JVP, crackles bilaterally, and bilateral lower extremity edema. EKG showed sinus tachycardia with PVCs and anteroseptal/lateral ischemic changes. Labs revealed troponin peaking in the 90s and leukocytosis. She underwent left and right cardiac catheterization revealing essentially clean coronaries, severely reduced LVEF 10-20%, severe hypokinesis of the inferoapical segments consistent with Takotsubo cardiomyopathy and hemodynamics consistent with cardiogenic shock. Cardiac MRI demonstrated findings consistent with myocarditis. The patient was successfully managed by a multidisciplinary team. Due to differential diagnoses of Takotsubo cardiomyopathy and myocarditis, serologies for cardiotropic viruses, urine toxicology, and autoimmune workup were performed and were negative. Therefore, an endomyocardial biopsy was obtained revealing lymphocytic and histiocytic infiltrates with localized areas of fiber necrosis. The lymphoid infiltrates were predominantly T-cells, highlighted with CD45 and CD3 stains, consistent with findings of lymphocytic myocarditis. <h3>Summary</h3> This case highlights lymphocytic myocarditis presenting similarly to Takotsubo cardiomyopathy in an older female. This is particularly thought-provoking given that myocarditis must be excluded in all cases of Takotsubo cardiomyopathy per the Mayo criteria. It illustrates the importance of recognizing the clinical presentation of myocarditis and distinguishing it from other secondary cardiomyopathies to properly manage these patients.

Молекулярні механізми патогенезу автоімунного тиреоїдиту Хашимото (огляд літератури)

The purpose of the study was to systematize and analyze material of recent studies on molecular mechanisms of pathogenesis of autoimmune Hashimoto's thyroiditis. Materials and methods. Analytical and bibliosemantic methods were used in the study. Results and discussion. Autoimmune Hashimoto's thyroiditis is a chronic inflammatory disease of the thyroid gland of autoimmune genesis in which impaired tolerance to thyroid autoantigens results in chronic progressive lymphoid infiltration followed by gradual destruction of thyroid parenchyma. The disease is more often observed at the age of 45-65 years and is multifactorial – both genetic predisposition and environmental factors contribute to its development. The ratio of female to male patients is approximately 10-20:1, and in recent years, the prevalence of autoimmune Hashimoto's thyroiditis has increased more than tenfold. On morphological examination, the section of the thyroid is diffusely enlarged, the surface of the section is pale, yellow-brown in color, dense and nodular. Microscopic examination reveals numerous large mononuclear inflammatory infiltrates in the parenchyma, consisting of small lymphocytes and plasma cells, well-formed germinal centers. A twin method is used to assess the degree of contribution of genetic and environmental factors. Studies demonstrate significantly greater concordance in monozygotic twins than in dizygotic twins, confirming the important role of genetic factors in the etiology. Among the main immune mechanisms of damage are: direct action of CD8+ cytotoxic T cells on thyrocytes by binding through the Fas-receptor – Fas ligand system; the influence of cytokines, in particular – interferon γ, produced by TH1 cells and leading to macrophage activation with subsequent damage to follicles, antibody-dependent cell-mediated cytotoxicity, in which Fc fragments of antibodies previously bound to thyroid cells are binding sites to cells that commit killing, in particular – to the natural killer cells. In terms of thyroid cell damage, cytokines produced by the lymphocytic infiltrate play a key role. These include differentiation, signal transduction, and stimulation of other cells to release proinflammatory mediators or synthesize antibodies. Their ability to stimulate the thyroid cells themselves to release inflammatory mediators should be noted, thereby enhancing and perpetuating the autoimmune process. Researchers have identified other mechanisms, and the ratio of their contribution to the overall pathological process is a matter of debate and may vary from patient to patient. One explanation may be the multifactorial nature of the disease. In particular, different genetic mutations can lead to different disorders of intracellular and intercellular signaling, but the resulting factor will be one – immune autoaggression. Conclusion. The pathogenesis of autoimmune Hashimoto's thyroiditis is complex and multifaceted, involving both humoral and cellular immunity. The disease may be provoked both by mutations in the mechanisms of immune regulation, by mutations in the thyroid cells themselves, and by environmental factors

Rare central nervous system lymphomas.

Central nervous system (CNS) lymphomas are rare malignancies characterised by lymphoid infiltration into the brain, spinal cord, cranial nerves, meninges and/or eyes in the presence or absence of previous or concurrent systemic disease. Most CNS lymphomas are of the diffuse large B‐cell lymphoma (DLBCL) subtype for which treatment strategies, particularly the use of high‐dose methotrexate‐based protocols and consolidation with autologous stem cell transplantation, are well established. Other histopathological subtypes of CNS lymphoma are comparatively less common with published data on these rare lymphomas dominated by smaller case series and retrospective reports. Consequently, there exists little clinical consensus on the optimal methods to diagnose and manage these clinically and biologically heterogeneous CNS lymphomas. In this review article, we focus on rarer CNS lymphomas, summarising the available clinical data on incidence, context, diagnostic features, reported management strategies, and clinical outcomes.

Lymphocytic thyroiditis

Sixty five cases of chronic lymphocytic thyroiditis were included in the study. Most of the study subjects were females [61 cases (94%)] and male to female ratio was 1:15. The most common age group was ? 40 years (52 cases, 80%). Grade I lymphocytic thyroiditis was observed in seventeen (17 cases, 26%) cases, Grade II in twenty eight cases (28 cases, 43.07%) and Grade III thyroiditis was seen in twenty (20 cases, 31%) cases. Anti-TPO and TSH values were increased in 95% (19/20) of cases with grade 3 lymphoid infiltrate, 92.8% (26/28) of cases with grade 2, and 94.1% (16/17) of cases with grade 1. The diagnosis of Hashimoto Thyroiditis should be based on a multidisciplinary approach wherein clinical, radiological, biochemical, cytological, and radionuclide parameters are taken into consideration. However, in spite of the availability of different diagnostic modalities, demonstration of lymphocytic infiltration on cytologic smears still remains the gold standard.

Characteristics of composition a lymphoid infiltrate in the tongue squamous cell carcinoma

Introduction. Squamous cell carcinoma of the tongue is the most common oral cancer. The tumor microenvironment has a significant impact on tumor progression; therefore, better understanding of its characteristics is crucial for the treatment strategy, since in some cases it modifies the tumor microenvironment resulting in tumor resistance to therapy.Study objective – to compare the number of CD8+Т-lymphocytes, CD57+NK-cells, and CD20+B-lymphocytes in the microenvironment of tongue squamous cell carcinoma in patients receiving and not receiving neoadjuvant chemoradiotherapy.Materials and methods. We performed immunohistochemical examination of specimens from 67 patients with tongue squamous cell carcinoma who did not receive neoadjuvant chemoradiotherapy. Eleven patients were diagnosed with well differentiated tumors (G1); 21 patients had moderately differentiated tumors (G2); and 35 patients had poorly differentiated tumors (G3). T1 tumors were observed in 11 individuals, T2 tumors – in 26 individuals, T3 tumors – in 26 individuals, and T4 tumors – in 4 individuals. We also examined 30 patients who had undergone neoadjuvant chemoradiotherapy, including external beam radiotherapy (total dose of 60 Gy) and a cycle of polychemotherapy (cisplatin and 5‑fluorouracil). Of them, 6 patients had T1 tumors, 17 patients – T2 tumors, 5 patients – T3 tumors, and 2 patients – T4 tumors. We measured the areas occupied by CD8+T-lymphocytes, CD20+B-lymphocytes, and CD57+NK-cells in the hot spots in the tumor microenvironment.Results. The number of CD8+T-lymphocytes in the tumor microenvironment was higher in patients after neoadjuvant chemoradiotherapy than in those who did not receive it (р = 0.000), whereas the number of CD20+B-lymphocytes was lower after neoadjuvant chemoradiotherapy. The area occupied by CD57+NK-cells in the hot spots of the tumor microenvironment did not differ significantly before and after therapy (p &gt;0.05).Conclusion. Thus, neoadjuvant chemoradiotherapy in patients with tongue squamous cell carcinoma caused an increase in the number of CD8+T-lymphocytes, a decrease in the number of CD20+B-lymphocytes in the tumor microenvironment, and had no effect on the population of CD57+NK-cells.

Use of Ultrasensitive RNA In Situ Hybridization for Determining Clonality in Cutaneous B-Cell Lymphomas and Lymphoid Hyperplasia Decreases Subsequent Use of Molecular Testing and Is Cost-effective.

Primary cutaneous B-cell lymphomas (PCBCLs) are diagnostically challenging entities due to significant overlap in clinical and morphologic features with reactive lymphoid proliferations. Traditional methods for evaluating clonality such as immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) are limited by low sensitivity, which leads to additional costly and time-consuming molecular clonality assays. More recent technology has introduced ultrasensitive bright-field RNA in situ hybridization (BRISH) to the field, which can detect single molecules of light-chain mRNA. The current study evaluated 274 cases of PCBCL in addition to atypical and reactive lymphoid infiltrates, with CISH or BRISH performed on 180 (65.7%). CISH was performed on 105 (58.3%), and BRISH was performed on 75 (41.7%). Significantly fewer immunoglobulin heavy-chain (IGH) rearrangement studies were performed on cases that were evaluated with BRISH as compared with CISH (P=0.02). Subgroup analysis demonstrated that cases with restriction by BRISH were significantly less likely to have subsequent IGH studies performed (P=0.01). The expected costs of cases using CISH versus BRISH were $1053.89 versus $810.32 to the patient and $245.63 versus $225.23 to the laboratory. The use of ultrasensitive BRISH to evaluate clonality in PCBCL reduced the use of IGH rearrangement studies when compared with CISH. In particular, cases with light-chain restriction by BRISH did not result in confirmatory molecular testing. Despite slightly higher costs to the laboratory to perform BRISH, routine use of this methodology can result in cost savings to both the patient and laboratory by decreasing the use of expensive molecular methods.

Subcutaneous parasitic infection in Slovenia: a case report

Filariasis is a parasitic disease caused by infection with roundworms of the Filarioidea superfamily. Depending on the species of roundworm, the disease can present itself in one of three forms. It can affect the lymphatic system, the subcutaneous tissue, or serous cavities. We present the case of a male patient from central Europe with a subcutaneous manifestation similar to filariasis. Laboratory findings showed eosinophilia and elevated levels of IgE antibodies, and histological examination of skin biopsy material showed granulation tissue with lymphoid and plasma cell infiltration. When the lesion was examined under a microscope following an excision, live wormlike parasites about 3.5 cm long were detected. Such parasitic infections are usually encountered in tropical regions and sometimes reported in travelers returning from endemic countries. Our patient, however, had never left Europe, which is what makes this case so interesting.

CHANGES IN THYROID NODULES CAUSED BY COVID-19, ACCORDING TO ULTRASOUND. FIRST OBSERVATIONS.

ObjectivesThe COVID-19 pandemic has posed a number of issues of medical and social significance to doctors of various specialties. In particular, the issue of the impact of COVID-19 on the course of chronic diseases and conditions is relevant and little studied.The aim of the work is to study changes in the structure of thyroid nodules after COVID-19 according to ultrasound data.MaterialsDynamic ultrasound examinations was performed in 39 patients with verified benign thyroid nodules and pseudonodular changes in autoimmune thyroiditis. The duration of follow-up before COVID-19 disease was 0.5-10 years, after the disease - 2-6 months.ResultsIn 8 (42%) of 19 patients with autoimmune thyroiditis, an increase in pseudonodes in size and the fusion of several small pseudonodes into large ones were noted without significant changes in echographic characteristics. Enlargement and fusion of pseudonodes can be caused by the intensification of lymphoid infiltration due to the activation of autoimmune processes determined by the COVID-19.In 11 (55%) of 20 patients with benign nodules, a change in their echostructure in the form of microcalcifications was noted, in 6 of them the nodule size increased. A possible cause of such changes may be the destruction of small blood vessels with pinpoint hemorrhages because of COVID-19, followed by their calcification. A fine-needle biopsy of the altered nodes was performed, in one case precancerous proliferation was detected.ConclusionsPostponed COVID-19 causes multidirectional changes in benign thyroid nodules, determined by ultrasound. Further studies are needed to assess their nature and impact on the course of the disease.

Acute Kidney Injury as an Initial Presentation in Mantle Cell Lymphoma- A Rare Case Report

Mantle Cell Lymphoma (MCL) is a rare aggressive lymphoid neoplasm accounting for 3-7% of all Non Hodgkin Lymphomas (NHL). Kidney involvement in MCL is rarely reported in biopsies from living patients, being caused by direct lymphoid infiltration. Only 19 cases have been documented of Acute Kidney Injury (AKI) with lymphomatous infiltration. This case report is of a 50-year-old male who presented with AKI and was found to have a MCL infiltrating the kidneys.

Waldenstrom Macroglobulinaemia with Signet Ring Cells: A Case Report

Waldenstrom Macroglobulinemia (WM) is an indolent lymphoproliferative disorder characterised by Immunoglobulin M (IgM) production and neoplastic lymphoid infiltrate. The morphology of the neoplastic cells show spectrum of maturation characterised by small lymphocytes, lymphoplasmacytoid cells and plasma cells. The infiltrate is predominantly lymphoid with relatively small population of plasma cells. The plasma cell morphology is commonly of mature type with basophilic cytoplasm, eccentric nucleus with clumped chromatin and perinuclear halo (hof). But incidence of signet ring cells in WM is very rare and only one case has been reported till date. Here, authors report an interesting case of a 61-year-old man who presented with on and off chest pain and later diagnosed as WM with signet ring cells. On examination, the patient was found to have anaemia and lymphadenopathy. Bone marrow aspirate cytology showed hypercellular particles and scattered signet ring like plasma cells with large globular cytoplasmic inclusions. Flow Cytometry (FCM) established the diagnosis by demonstrating the clonal nature of plasma cells and B-lymphoid cells. Immunofixation confirmed the presence of monoclonal protein of IgM lambda type. The cytoplasmic content in these signet ring plasma cells is probably the accumulated IgM due to the defect in releasing. Clustering of these signet ring cells in marrow may raise a suspicion of metastatic adenocarcinoma and should not be misinterpreted.

Патоморфологическая диагностика первичного кожного CD4-позитивного Т-клеточного лимфопролиферативного заболевания из мелких и средних клеток: серия из 28 случаев

Introduction. Primary cutaneous CD4+ lymphoproliferative disorder of small and medium cells (PC CD4+ T-LPD small/medium cell) is a new entity identified in the WHO classification published in 2017. The aim of the research was to characterize morphological and immunohistochemical features of PC CD4+ T-LPD small/medium cell. Materials and methods. The study examined 28 skin biopsies from 13 males and 15 females with PC CD4+ T-LPD small/medium cell using histological and immunohistochemical methods. Results. We detected growth pattern to be of nodular, focal–diffuse, and diffuse types. Each case was characterized by significant T-cell lymphoid infiltration with an immunophenotype of follicular T-helper cells (Tfh-immunophenotype), the number of B-cells varying. Conclusion. PC CD4+ T-LPD from small and medium cells is a rare disease that requires further study to determine the criteria for diagnosis and treatment. Keywords: primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, T follicular helper cells, immunophenotype

Особливості лімфоїдного мікрооточення в інвазивному протоковому раку грудної залози

The purpose of the study was to assess the distribution of tumor-infiltrating T-, B-lymphocytes and natural killer cells in various molecular subtypes of invasive ductal breast cancer and to establish their relationship with the degree of tumor differentiation. Materials and methods. The basis of the scientific work was a complex morphological, including immunohistochemical study of 193 cases of invasive ductal breast cancer. General histological processing of the samples was carried out in accordance with the standard technique. Immunohistochemical studies for CD3, CD20, CD56, ER, PR, c-erbB2, Ki-67 were performed according to the manufacturer's protocol with the control of samples. The grade of malignancy was determined according to the modified scheme of P. Scarff, H. Bloom and W. Richardson. The presence, localization, and expression intensity of diagnostic and prognostic biomarkers CD3, CD20, and CD56-positive cells (T-, B-, and natural killer cells, respectively) were determined using the new bioimage analysis software QuPath. Results and discussion. The differences obtained in our study varied depending on the subpopulations of immune cells and their location in the tumor tissue. The density of T and B lymphocytes was higher within the tumor and in the invasive margin in the non-luminal phenotypes compared to the luminal A and B phenotypes. Compared to the density of T-lymphocytes, the B-cell infiltrate was significantly (p &lt;0.01) less pronounced in tumors of both luminal and non-luminal phenotypes. The lowest density of natural killer cells among tumor-infiltrating lymphocytes was found within the tumor of luminal subtypes. The percentage of infiltrates of T and B cells both within the tumor focus and in the invasive margin, as well as natural killer cells in the invasive margin, was significantly lower with G1 and G2 than with the degree of differentiation G3 (p &lt;0.01). As for intratumoral natural killer cells, differences were found only between the degree of differentiation of G2 and G3, and the differences between G1 and G2 were not statistically significant (p&gt; 0.05). Qualitative and quantitative assessment of the intensity of expression of T-, B- and natural killer cells also demonstrated a different degree of expression of lymphocytes, depending on the molecular subtype and location of the infiltrate. The luminal subtype A was characterized by a significant predominance of mild expression (2+) CD3 both within the tumor and in the invasive margin of the tumor (p &lt;0.05), while in the luminal B and Her2 + phenotypes, the intensity of CD3 expression prevailed at the 1+ level. Triple negative tumors were characterized by strong expression of (3+) CD3 within the tumor and in the invasive margin of the tumor in all cases studied. Conclusion. Thus, tumor-infiltrating lymphocytes in different molecular subtypes of invasive ductal breast cancer can be considered a prognostic biomarker. Our results indicate a relationship between lymphoid infiltrate and the degree of differentiation in invasive ductal breast cancer, especially in less favorable molecular subtypes

Pagetoid reticulosis

Pagetoid reticulosis (PR) is a rare type of mycosis fungoides. Clinical symptoms of PR can mimic other skin diseases of papulosquamous, neoplastic, and infectious origin that hampers PR diagnostics. The main histopathologic feature of PR is dense intraepidermal infiltration by medium to large-size lymphocytes through the epidermis leading to pagetoid plaque formation. There are three common immunophenotypes of PR: CD4-positive T-helper phenotype (CD3+, CD4+, CD8); T-cytotoxic/suppressor (CD3+, CD4, CD8+); and double negative phenotype (CD3+, CD4, CD8). The clinical case of PR with rare immunophenotype (CD2+, CD3+, CD8+ lymphoid infiltrate) is presented. The careful analysis of the symptoms, pathomorphological and immunohistochemical data is necessary for accurate PR diagnostics.

Serum HIF-1α and TGF-β1 levels depending on the clinical and morphological characteristics of breast cancer and sensitivity of tumor to neoadjuvant chemotherapy

Purpose of the study. To assess the serum levels of HIF-1 α and TGF-β1 in patients with invasive breast cancer (BC) depending on the clinical and morphological characteristics, molecular biological subtypes and the degree of pathological response (PR) of the tumor and metastases in the regional lymph nodes.Materials and methods. 65 patients with newly diagnosed invasive BC, of whom 32 received from 6 to 8 courses of neoadjuvant chemotherapy (neo-A-CT) were included in this pilot study. The levels of TGF-β1 and HIF-1α were determined by enzyme-linked immunosorbent assay. Statistical analysis was performed using the Statistica 12.0 software.Results. It was found that a high level of TGF-β1 was significantly more often observed in HER2-positive and I-IIa stages of luminal A and triple-negative BC (p = 0.01). HIF-1a levels were significantly higher in the presence of distant metastases (p = 0.04) and slightly higher in the presence of microcalcifications on mammograms (p = 0.07).The analysis showed that patients with grade III-IV of PR in tumor were significantly younger (p = 0.047). Grade III-IV of PR in tumor was significantly more often observed in G3 (p = 0.05), in Her2-positive and triple negative BC (p = 0.01), in the absence of perineural (p = 0.002) and lymphovascular invasion (LVI) (p = 0.045), in the presence of lymphoid infiltration (p = 0.011) and microcalcifications in the tumor (p = 0.043), and slightly higher in ductal BC (p = 0.08). No significant correlations were found between the levels of TGF-β1 and HIF-1a and tumor PR (p = 0.6 and p = 0.9, respectively). However, in patients with grade III-IV of PR in regional metastases, the level of TGF-β1 was significantly lower than in patients with grade I-II (p = 0.03).Conclusions. Thus, these data indicate the presence of correlations between the levels of HIF-1 α and TGF-β1 in the blood serum and a number of clinical characteristics of BC. The highest levels of HIF-1α are observed in the presence of distant metastases, and the highest levels of TGF-β1 are noted in HER2-positive and I-IIa stages of luminal A and triple-negative breast cancer. Given the presence of significant correlations between the level of TGF-β1 and the degree of PR in regional lymph nodes, its determination may be useful for assessing the sensitivity of metastases to regional lymph nodes to the neo-A-CT.

IMMUNOHISTOCHEMICAL FEATURES IN SOFT TISSUE SARCOMAS

Sarcomas are relatively rare, accounting for only 1% of all adult malignancies and 15% of childhood malignancies [2]. According to the World Health Organization (WHO), the group of soft tissue sarcomas includes more than 100 different histological subtypes [3]. According to the recommmendations of the WHO to improve the accuracy of diagnosis in soft tissue sarcoma, the traditional histopathological examination should be supplemented with immunohistochemical and molecular methods [1]. It was carried out immunohistochemical research of CD31 receptor of Vascular Endothelial Growth Factor (VEGF) in 129 patients with STS. The age range of patients is on average 14-77 years with a peak in the age of 50-59 years. The most common reason for initial visit to a medical institution was palpable tumor (100%). It was studied the following correlative interdependences: It was determined that histodifferentiation of tumour is in inverse correlation with expression CD31 receptor. Distinctions of expression level of CD31 are shown, depending on the degree of tumor differentiation, presence or absence of its spontaneous necrotization, limphoid infiltration of pathological nidus and amount of vessels in tumor tissue. That is as high the degree of histological differentiation of tumour as low the level of expression CD31 receptor (χ2=35,4; p&lt;0,001; р=-0,322). In FHTof ST is exposed inverse dependence between expression CD31 endotelial cells with spontaneous necrosis and lymphoid infiltration. As more the size and foci of spontaneous necrosis (χ2=67,1; p&lt;0,001; р=-0,473) and lymphoid infiltration (χ2=46,1; p&lt;0,001; р=-0,346), as low the level of expression CD31 receptor. It was found that the high level of espression CD31 receptor is in direct correlation with metastasis (χ2=18,6; р=0,42; p&lt;0,001) and recurrence (χ2=9,43; р=0,30; p&lt;0,01) of the process. Studied modern approaches to the diaqnostics and treatment of malignancies. One such approach is ”Oncology Control”, which means minimizing the risk of recurrence at the local and systemic level. Following treatment, follow-up should include history and physical examination accompanied by imaging (Ultrasound or MRI) every 3 to 6 month for 2 to 3 years, and then every 6 to 12 months thereafter to asses for recurrence. So in high positivity of CD31 receptor is exposed unfavourable prognosis in patients with STS. Summarizing before said we have come to the conclusion that immune-histo-chemical investigation of CD31 receptor of VEGF has important prognostical meaning in patients STS.

Quantitative assessment of the immune microenvironment in African American Triple Negative Breast Cancer: a case\u2013control study

PurposeTriple negative breast cancer (TNBC) is more common in African American (AA) than Non-AA (NAA) population. We hypothesize that tumor microenvironment (TME) contributes to this disparity. Here, we use multiplex quantitative immunofluorescence to characterize the expression of immunologic biomarkers in the TME in both populations.Patients and methodsTNBC tumor resection specimen tissues from a 100-patient case: control cohort including 49 AA and 51 NAA were collected. TME markers including CD45, CD14, CD68, CD206, CD4, CD8, CD20, CD3, Ki67, GzB, Thy1, FAP, aSMA, CD34, Col4, VWF and PD-L1 we quantitatively assessed in every field of view. Mean expression levels were compared between cases and controls.ResultsAlthough no significant differences were detected in individual lymphoid and myeloid markers, we found that infiltration with CD45+ immune cells (p = 0.0102) was higher in TNBC in AA population. AA TNBC tumors also had significantly higher level of lymphocytic infiltration defined as CD45+ CD14− cells (p = 0.0081). CD3+ T-cells in AA tumors expressed significantly higher levels of Ki67 (0.0066) compared to NAAs, indicating that a higher percentage of AA tumors contained activated T-cells. All other biomarkers showed no significant differences between the AA and NAA group.ConclusionsWhile the TME in TNBC is rich in immune cells in both racial groups, there is a numerical increase in lymphoid infiltration in AA compared to NAA TNBC. Significantly, higher activated T cells seen in AA patients raises the possibility that there may be a subset of AA patients with improved response to immunotherapy.

Abstract 11421: The M2 Gene is a Determinant of Reovirus-Induced Myocarditis

Although a broad range of viruses can cause myocarditis, the mechanisms that underlie virus-induced cardiac inflammatory disease are poorly understood. Here, we use mammalian orthoreovirus (reovirus) to examine mechanisms of viral myocarditis. We found that the M2 gene is a determinant of reovirus myocarditis in neonatal mice. The M2 gene encodes viral outer capsid protein μ1, which mediates host membrane penetration during viral entry. A recombinant reovirus in which the M2 gene from strain T3D was substituted into an otherwise strain T1L genetic background (T1L/T3DM2) caused significantly more myocarditis than the parental T1L strain. T1L was non-lethal in wild-type mice, whereas greater than 90% of mice succumbed to T1L/T3DM2. T1L/T3DM2 produced higher viral loads at the site of inoculation and disseminated with more rapid kinetics than T1L. T1L/T3DM2 also produced higher peak viral titers compared to T1L, most notably in the heart where T1L/T3DM2 viral loads were approximately 50-fold higher than T1L. Hearts from T1L-infected animals contained small purulent lesions, consistent with previous reports that T1L is mildly myocarditic. In contrast, hearts from T1L/T3DM2-infected mice were grossly abnormal, with extensive pericardial inflammatory infiltrate. Histological analysis revealed that T1L/T3DM2-infected hearts had larger and more frequent heart lesions containing necrotic cardiomyocytes with pyknotic debris than animals infected with T1L. T1L/T3DM2 also induced more lymphocyte and histiocyte infiltration than T1L. More cells with activated caspase-3 were found in hearts infected with T1L/T3DM2. Flow cytometry profiling of cardiac immune cells revealed that T1L/T3DM2 induced significantly more lymphoid cell (CD4 + and CD8 + T cells) and inflammatory monocyte infiltration than T1L. Together, our findings indicate that the M2 gene, and by extension the μ1 protein, promotes reovirus replication in the heart, leading to increased cardiac inflammation and enhanced myocarditis.

Clinical, Morphological, and Immunohistochemical Justification of Surgery for Chronic Appendicitis in Children.

Objective: Chronic appendicitis (CA) is a diagnosis characterized by long-standing right lower quadrant pain. We analyzed clinical, morphological, and immunohistochemical studies of the appendix to confirm the adequacy of surgery for CA in children with chronic right lower quadrant pain. Patients and Methods: We carried out comparative studies of clinical presentations and results of morphological and immunohistochemical studies of remote appendicitis in 55 children with chronic recurrent lower quadrant pain (CRLQP). Results: Morphological and immunohistochemical studies revealed three types of changes in the appendix. Type 1 (n = 21)-chronic inflammation. Inflammatory leukocyte infiltration was localized within the mucous membrane of the appendix. An immunohistochemical study revealed a significant (P < .01) increase in the expression of CD106 (vascular cell adhesion molecule 1) and in the number of matrix metalloproteinase 9 (MMP-9) positive cells. Type 2 (n = 20)-lymphoid hyperplasia. Morphological changes were characterized by lymphoid infiltration of the mucosa and submucosa of the appendix. Immunological changes were characterized by an increase (P < .01) in the expression and number of MMP-9, expression of CD106 positive cells, an increase in the expression of collagen IIIα in combination with a decrease in the expression and number of positive vascular endothelial growth factor (VEGF) and vasoactive intestinal peptide cells. Type 3 (n = 12)-catarrhal inflammation. Morphological changes were characterized by impaired blood circulation only in the mucous membrane, without destructive or inflammatory changes. Immunological changes were characterized by an increase (P < .01) in the expression and number of VEGF-positive cells, which may indicate a response to local hypoxia of the appendix and explain neovascularization in a chronic condition. The abdominal syndrome after appendectomy was noted to disappear in 89% of patients. The established changes in remote appendicitis, other than acute inflammation, make it possible to consider reasonable appendectomy a way of treating CRLQP in children. Conclusions: We have identified immunohistochemical and morphological changes pointing to autoimmune and vascular mechanisms of appendix damage in children with CRLQP. Laparoscopic appendectomy helps to eliminate abdominal pain in most CA patients.

Hashimoto type thyroiditis

Thyroiditis (struma limfomatosa - Hashimoto's disease) is a two-sided diffuse dense goiter, intimately fused with the trachea. Fusion with other organs and tissues is not observed. At the same time, the thyroid gland is often slightly enlarged and can cause compression of the trachea, which leads to hoarseness. The disease usually affects older women over 40 years of age (Babcock). On the cut, the tissue of the thyroid gland is dense, whitish, with significant lymphoid infiltration, proliferation of connective tissue, atrophy of the glandular tissue and degeneration of the epithelium. Struma Hashimoto was considered a disease of the Anglo-Saxon countries, where about 200 observations are described. However, in recent years, the domestic literature has been significantly enriched with reports of chronic lymphoid thyroiditis.