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Introduction: BRAFV600E mutation (BRAFmut) is common in papillary thyroid cancer (PTC), and most patients have an excellent outcome. However, a TERT-promoter mutation (pTERTmut) in the presence of BRAFmut (BRAFmutpTERTmut) has been demonstrated to confer a more aggressive behavior to PTC. Lymphocytic infiltration is often present in PTC. In this study, we sought to decipher the relationship between the BRAF and pTERT mutations and immune gene dysregulation in tumor samples from a cohort of 147 samples of PTC. Methods: The abundance of 770 immune gene transcripts was determined by multiprex capture/detection and digital counting of mRNA transcripts using the NanoString nCounter® PanCancer Immune Profiling Panel. Results: We identified 40 immune transcripts differentially expressed in BRAFmutpTERTmut vs BRAFmutpTERT wildtype (pTERTwt) (P <0.05). Transcripts induced by BRAFmut alone were significantly repressed in BRAFmutpTERTmut samples, such as genes expressed by lymphoid cells, antigen-presenting cells, and cytotoxic cells, including chemokines, cytokines, checkpoint control proteins, interferon downstream markers, TNF superfamily proteins and BMP markers. A validation analysis using 444 samples from The Cancer Genome Atlas (TCGA) PTC dataset yielded similar results. Deconvolution analysis confirmed differences in the immune cell populations such as increased presence of M2 macrophages in the BRAFmutpTERTmut Mayo cohort and a lower abundance of M1 macrophages in the BRAFmutpTERTmut TCGA cohort compared to BRAFmutpTERTwt. Most of the immune gene pathways were enriched in the BRAFmutpTERTwt tumors in both Mayo and TCGA cohorts but not in BRAFmutpTERTmut. BRAFmutpTERTwt had higher stromal lymphocytes infiltration as compared to BRAFwtpTERTwt tumors, corroborating the transcriptomic findings. Discussion: To our knowledge this is the first report of a potential link between TERT and the immune microenvironment, offering an explanation for the aggressive nature of BRAFmutpTERTmut PTC. [ABSTRACT FROM AUTHOR]

Background: Thyrotoxicosis is a clinical condition induced by tissue exposure to excess free thyroid hormones, especially thyroxine (T4) and/or triiodothyronine (T3). Aim: This study aimed to determine the relation between the lymphocytic infiltration degree and the postoperative manifestations of either recurrence or hypothyroidism. Patients and methods: This prospective comparative research was performed on one hundred cases of thyrotoxic goiter admitted to Mansoura University Endocrine Surgery Unit from December 2021 to December 2023. Results: The lymphocytic infiltration degree in the removed thyroid specimen was recorded. The majority of our patients were classified as grade 0 in 29 patients (29%), followed by grade 3 in 25 patients (25%), grade 1 in 23 patients (23%) and grade 2 in 23 patients (23%). They were separated into two equal groups. Six patients (12%) in group “A” who underwent total thyroidectomy (TT) showed hypothyroid manifestations, where there was grade 0 and grade 1 lymphocytic infiltration in specimens which can be corrected by giving levothyroxine (EltroxinTM). Four patients (8%) in group “B” who underwent near total thyroidectomy (NTT) showed recurrence of thyrotoxic manifestations where there was grade 2 and grade 3 lymphocytic infiltration in specimens which can be corrected by radioactive Iodine (RAI). Conclusion: Postoperative hypothyroidism was detected in 12 patients with mild lymphocytic infiltration after TT, while recurrence was observed in 8 patients with heavy lymphocytic infiltration after NTT in patients with thyrotoxic goiter. [ABSTRACT FROM AUTHOR]

IntroductionBRAFV600E mutation (BRAFmut) is common in papillary thyroid cancer (PTC), and most patients have an excellent outcome. However, a TERT-promoter mutation (pTERTmut) in the presence of BRAFmut (BRAFmutpTERTmut) has been demonstrated to confer a more aggressive behavior to PTC. Lymphocytic infiltration is often present in PTC. In this study, we sought to decipher the relationship between the BRAF and pTERT mutations and immune gene dysregulation in tumor samples from a cohort of 147 samples of PTC.MethodsThe abundance of 770 immune gene transcripts was determined by multiprex capture/detection and digital counting of mRNA transcripts using the NanoString nCounter® PanCancer Immune Profiling Panel.ResultsWe identified 40 immune transcripts differentially expressed in BRAFmutpTERTmutvs BRAFmutpTERT wildtype (pTERTwt) (P

It is stated that Hashimoto's Thyroiditis (HT) is a risk factor for the development of Papillary Thyroid Cancer (PTC). However, the effect of HT on the coexistence of HT and PTC is still controversial. In this study, our aim is to investigate the effect of the presence of HT on clinicopathological data in patients with PTC. All 356 patients whose pathology was reported as PTC who were operated between 2015 and 2023 were included in the study. PTC patients were divided into 2 groups as those with and without HT. The effect of HT association on clinicopathological features was investigated. In 356 PTC patients, the rate of HT was 31.2%. PTC patients with HT had less multifocality (p < 0.05), more lymph node metastases (LNM) (p < 0.01) compared to PTC patients without HT. The presence of HT did not affect the bilaterality of the tumor, tumor diameter, lymphovascular invasion, or capsule invasion. While multifocality was observed less frequently in PTC patients with HT, lymph node metastasis rates were higher. [ABSTRACT FROM AUTHOR]

Lingjia Li,1 Yulan Wang,2 Hua Gu2 1Department of Dermatology, Jiangnan University Medical Center, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Kunming Medical University Kunming, Kunming, People’s Republic of ChinaCorrespondence: Hua Gu, Department of Dermatology, The first Affiliated Hospital of Kunming Medical University Kunming, Kunming, People’s Republic of China, Tel +86-18762675765, Email guhua1978@sina.comAbstract: We report a case of rash in a 35-year-old female presenting with erythematous papules and infiltrative plaques on the nose and upper jaw resembling rosacea. The patient had been experiencing these symptoms for one year. A pathological biopsy revealed an inflammatory infiltrate consisting of dense perivascular lymphocytes surrounding hair follicles and sweat glands in the dermis. Immunohistochemistry demonstrated a predominance of CD4+ T cells compared to CD8+ T cells. Based on the clinical manifestations, histopathology, and immunohistochemistry, the patient was diagnosed with Jessner’s Lymphocytic infiltration of the skin (JLIS). The patient was treated with oral Minocycline, 100mg twice daily. After 4 weeks, the dosage was reduced by half and the treatment continued for 2 months, resulting in complete resolution of the rash. The clinical presentation resembled rosacea, and this particular manifestation of JLIS has not been previously reported. Treatment with minocycline yielded satisfactory efficacy, and no recurrence has been observed for 5 year.Keywords: lymphocytic infiltration, skin, rosacea, minocycline

Introduction: Thyroid lymphomas are a rare finding among thyroid malignancies, and Chronic Lymphocytic B-cell (CLL-B) type of thyroid lymphoma is even more infrequent. Lymphomas compose only 2% of thyroid malignancies, with primary thyroid lymphomas constituting only 2.5% of all lymphomas. Chronic lymphocytic B-cell (CLL-B) type of thyroid lymphoma (CLL-B) is is exceptionally rare, with only 4% of cases ever reported worldwide. Case Presentation: A55-year-old female presented with a complaint of swelling over the anterior part of neck. She had a pre-existing diagnosis of CLL, fine needle aspiration biopsy (FNAB)of the swelling revealed lymphocytic proliferation, classified as Bethesda grade II. The patients was in a euthyroid state and a 'core-needle' biopsy was performed to confirm the diagnosis of lymphocytic infiltration of the thyroid. The patient was managed conservatively and is currently under regular follow-up. Conclusions: The occurrence of thyroid swelling in CLL is a rare phenomenon, and confirming the diagnosis through biopsy is recommended. Surgeons should be cautious not to be deceived by the rarity of the swelling and avoid unnecessary surgical interventions. Conservative management has been the prevailing approach in the literature. This case report serves to support this conservative approach and contributes to the existing literature on Thyroid lymphoma due to CLL. [ABSTRACT FROM AUTHOR]

Introduction: Carcinoma of the stratified squamous epithelium of the oral cavity - oral squamous cell carcinoma (OSCC) is an invasive pathological lesion of the epithelium with varying degrees of squamous differentiation. It is characterized by early and extensive metastases, infiltration of adjacent anatomical structures, frequent recurrences, and a relatively low five-year survival rate of less than 50%. The aim of the study to determine the correlation between the analysis of the lymphocytic infiltrate of biopsy specimens with pathohistologically proven metastases of oral squamous cellular carcinoma on postoperative neck dissection specimens. Material and methods: The study included 42 patients with pathohistologically verified oral squamous cellular carcinoma who underwent surgery at the Department of Maxillofacial Surgery of the Clinic of Dental medicine in Niš in the period from 2018 to 2022. The histopathological analysis included the depth of tumor invasion, histopathological analysis of the lymph nodes of neck dissections, analysis of lymphocytic infiltration, and presence of lymphovascularand perineural invasion. Results: It was determined that the depth of invasion is statistically significantly different regarding the degree of lymphocytic infiltration (p=0.004). Invasion of over 4mm was present in 20% of patients with high infiltration, 44.4% of patients with medium infiltration, and 85.7% of patients with low infiltration. Conclusion: Given that the results of the study indicate that the analysis of the lymphocytic infiltrate can be a reliable predictive factor of the appearance of metastases in the lymph nodes of the neck, further research should be directed toward as sociating lymphocytic infiltration with certain biochemical and genetic parameters based on which a plan can be created for neck treatment in the N0 stage of oral squamous cellular carcinoma.

Copyright of Acta Stomatologica Naissi is the property of Clinic of Stomatology Nis and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Testicular torsion is a commonly encountered medical emergency in children. A 10-year-old boy with diagnostically confirmed leukemia presented with new onset testis swelling. Scrotal ultrasound showed absent blood flow on the left, consistent with acute testicular torsion. The patient underwent left orchiectomy due to the testis being unsalvageable. Later pathology confirmed lymphoblastic infiltrates. A malignancy of the testicles is rarely associated with torsion and, in the setting of leukemia, suggests widespread disease. Due to the risk of scrotal violation, an inguinal approach is preferable for surgical exploration of the testicles in patients with a history of leukemia.

Objective: This study aims to evaluate the relationship between the local immune response such as peritumoral and intratumoral lymphocytic infiltration and stromal reaction, with prognosis and other clinicopathological parameters in high-risk endometrioid carcinomas. Method: Totally 98 high-risk cases diagnosed as endometrioid carcinoma in our center between 2005 and 2017, were retrieved from the pathology archives and re-evaluated. Results: Totally 98 cases diagnosed as high-risk endometrial carcinoma were evaluated. Intratumoral and peritumoral lymphocytic infiltration was compared to overall survival period and overall survival was significantly higher in tumors showing peritumoral and intratumoral lymphocytic infiltration (p=0.000 <α=0.05, p=0.008 <α =0.05). However, a similar relationship between stromal reaction and overall survival rate was not detected. Intratumoral and peritumoral lymphocytic infiltration was compared to recurrence-free survival and recurrence-free survival period was significantly higher in cases showing either type of lymphocytic infiltration (p=0.003 <α =0.05, p=0.050 <α=0.05). Conclusions: Presence of peritumoral and intratumoral lymphocytic infiltration positively affects prognosis, similar to results of other studies. These parameters are important and necessary in predicting the prognosis of the patients and they should be included in pathology reports. [ABSTRACT FROM AUTHOR]

Cancer treatment-related adverse events (AEs) are sometimes associated with outcomes for cancer patients, especially with the newest therapies such as target therapy and immunotherapy. A few years ago, the first-line therapy for hormonereceptor-positive metastatic breast cancer (mBC) patients has been deeply changed by the introduction of cyclin-dependent kinase (CDK) 4/6 inhibitors, and now, we are improving our knowledge about their AEs and significance in clinical practice. Here, we report our experience with two cases of vitiligo-like lesions that occur early during treatment with ribociclib. We tried to change the CDK4/6 inhibitor for one patient, but the skin reaction persisted. Both patients retained only the endocrine therapy alone and had an unexpected durable progression-free survival (PFS). Some data on skin toxicities, including vitiligolike lesions by CDK4/6 inhibitors, have recently been reported in the literature, but for the first time, we highlight a possible correlation with improved survival outcomes of patients. Uncovering the etiology of this toxicity, verifying the involvement of the immune system, and demonstrating a possible positive impact in survival represent an intriguing research objective for the near future. [ABSTRACT FROM AUTHOR]

Abstract Background While contributions of dyslipidemia to autoimmune diseases have been described, its impact on thyroid autoimmunity (TA) is less clear. Programmed cell death 1(PD-1)/PD-ligand 1 (PD-L1) immune checkpoint is crucial in preventing autoimmune attack while its blockade exacerbates TA. We thus unveiled the effect of high-fat diet (HFD) on TA, focusing on the contribution of PD-1/PD-L1. Methods Female Sprague Dawley (SD) rats were randomly fed with a regular diet or HFD (60% calories from fat) for 24 weeks. Then, thyroid ultrasonography was performed and samples were collected for lipid and thyroid-related parameter measure. Results HFD rats exhibited hyperlipemia and abnormal biosynthesis of the unsaturated fatty acid in serum detected by lipidomics. These rats displayed a relatively lower echogenicity and increased inflammatory infiltration in thyroid accompanied by rising serum thyroid autoantibody levels and hypothyroidism, mimicking human Hashimoto’s thyroiditis. These alterations were concurrent with decreased mRNA and immunostaining of intrathyroidal PD-1 and also serum PD-1 levels but not the PD-L1 expression, suggesting a role of a PD-1 pathway. Meanwhile, the infiltration of B and T cell, a key cellular event inhibited by the PD-1 signals, was enhanced in the thyroid of HFD rats, along with thyroid fibrosis and apoptosis. Conclusions Our data suggest that HFD triggers TA through a mechanism possibly involving downregulation of PD-1-related immunosuppression, providing a novel insight into the link between dyslipidemia and autoimmune toxicities.

Cancer treatment-related adverse events (AEs) are sometimes associated with outcomes for cancer patients, especially with the newest therapies such as target therapy and immunotherapy. A few years ago, the first-line therapy for hormone-receptor-positive metastatic breast cancer (mBC) patients has been deeply changed by the introduction of cyclin-dependent kinase (CDK) 4/6 inhibitors, and now, we are improving our knowledge about their AEs and significance in clinical practice. Here, we report our experience with two cases of vitiligo-like lesions that occur early during treatment with ribociclib. We tried to change the CDK4/6 inhibitor for one patient, but the skin reaction persisted. Both patients retained only the endocrine therapy alone and had an unexpected durable progression-free survival (PFS). Some data on skin toxicities, including vitiligo-like lesions by CDK4/6 inhibitors, have recently been reported in the literature, but for the first time, we highlight a possible correlation with improved survival outcomes of patients. Uncovering the etiology of this toxicity, verifying the involvement of the immune system, and demonstrating a possible positive impact in survival represent an intriguing research objective for the near future.

In preclinical studies, which are conducted to study the therapeutic effectiveness and pharmacological safety of biologically active compounds for the correction of autoimmune thyroiditis, various experimental models of this pathology are used in the experiment. In this work, we analyzed various models of thyroiditis that have been used for the past fifty years. Such an analysis made it possible to choose the most optimal model for the study of autoimmune pathology of the thyroid gland as well as for the correction of this condition. The analysis of known and the search for new pathogenetically justified models of autoimmune diseases of endocrine organs is a very urgent task. The aim of the work was to study the dynamics of changes in the histomorphological structure of the thyroid gland when modeling autoimmune thyroiditis in rats using an allogeneic antigen isolated from the human thyroid gland. The postoperative thyroid gland of a person was used as an antigen. Morphological changes in the thyroid gland were studied one, three and six months after the end of the simulation. It was found that the use of this type of immunization led to changes in the parenchyma of the gland, characteristic of autoimmune thyroiditis. Already one month after modeling, Gürtle cells, fibrosis, areas of lymphoid infiltration of the parenchyma were registered. These pathological changes persisted and worsened three and six months after the end of the simulation. The investigated type of model of experimental autoimmune thyroiditis is easily reproduced. Pathological changes in the gland deepen over time and are comparable to those that occur in people with Hashimoto's thyroiditis. [ABSTRACT FROM AUTHOR]

Background: Our study has immunohistochemically examined T cells localization and number as well as proliferative activity level for the bulbourethral gland epithelium in men of different ages, using monoclonal antibodies against CD45RO and proliferating cell nuclear antigen (PCNA). Results: We have found that the T cells have been localized mainly in excretory ducts epithelium of the glands in any age group, meanwhile their relative number varies with age. The excretory ducts epithelium has shown a high proliferative activity when in acini the PCNA index has been low. Postnatal dynamics of the epithelium proliferative activity positively correlates with age-related density fluctuations in lymphocytic infiltration of the glands. Conclusions: We consider that intraepithelial T cells may contribute to the regulation of epithelial cells proliferation in the bulbourethral glands.

Background: While contributions of dyslipidemia to autoimmune diseases have been described, its impact on thyroid autoimmunity (TA) is less clear. Programmed cell death 1(PD-1)/PD-ligand 1 (PD-L1) immune checkpoint is crucial in preventing autoimmune attack while its blockade exacerbates TA. We thus unveiled the effect of high-fat diet (HFD) on TA, focusing on the contribution of PD-1/PD-L1. Methods: Female Sprague Dawley (SD) rats were randomly fed with a regular diet or HFD (60% calories from fat) for 24 weeks. Then, thyroid ultrasonography was performed and samples were collected for lipid and thyroid-related parameter measure. Results: HFD rats exhibited hyperlipemia and abnormal biosynthesis of the unsaturated fatty acid in serum detected by lipidomics. These rats displayed a relatively lower echogenicity and increased inflammatory infiltration in thyroid accompanied by rising serum thyroid autoantibody levels and hypothyroidism, mimicking human Hashimoto's thyroiditis. These alterations were concurrent with decreased mRNA and immunostaining of intrathyroidal PD-1 and also serum PD-1 levels but not the PD-L1 expression, suggesting a role of a PD-1 pathway. Meanwhile, the infiltration of B and T cell, a key cellular event inhibited by the PD-1 signals, was enhanced in the thyroid of HFD rats, along with thyroid fibrosis and apoptosis. Conclusions: Our data suggest that HFD triggers TA through a mechanism possibly involving downregulation of PD-1-related immunosuppression, providing a novel insight into the link between dyslipidemia and autoimmune toxicities. [ABSTRACT FROM AUTHOR]

Purpose: The immune response within colorectal cancer is widely studied and evaluated. The presence of lymphocytic infiltration in the main mass of the tumor and its front indicates a different clinical course of the disease. The aim of the study was to presence of CD3+ T lymphocyte infiltration in the tumor and its front in correlation with clinicopathological parameters. Materials and Methods: The study included a group of patients operated on due to colorectal cancer. The histopathological results of the patients were analyzed, including the assessment of the expression of CD3 lymphocytes in the main mass of the tumor and its front, and an analysis of correlation with the patient's age, sex, histological malignancy stage, presence of metastases to lymph nodes and distant metastases was performed. Results: We found the correlation between the differential infiltration from CD3+ T lymphocytes in the front of the invasion and the depth of tumor infiltration (p=0.008). But we do not found the correlation between the expression of CD3 in the main tumor mass and expression CD3 of the invasion front and patient's age, sex, tumor location, histological type of the tumor, histological grade, the presence of metastases to lymph nodes and the presence of distant metastases. Conclusions: The obtained results suggest a relationship between the intensity of the CD3+ T lymphocyte infiltration in the front and the depth of the colorectal cancer infiltration. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer cells are infiltrated by different types of immune cells. They are scattered throughout the medulla, stroma, and glands of the tumor, as well as in the invasive margin and in organized lymphoid follicles distant from the cancerous lesion. The aim of the study was to presence of CD8+ T lymphocyte infiltration in the tumor and its front in correlation with clinicopathological parameters. Materials and Methods: The study included a group 62 of patients operated on due to colorectal cancer. The histopathological results of the patients were analyzed, including the assessment of the expression of CD8+ T lymphocytes in the main mass of the tumor and its front, and an analysis of correlation with the patient's age, sex, histological malignancy stage, presence of metastases to lymph nodes and distant metastases was performed. Results: Statistical significance was demonstrated for the correlation between the differentiation of TCD8+ infiltration in the invasion front and the presence of distant metastases (p = 0.041). Statistical significance was demonstrated for the correlation between the differentiation of TCD8+ infiltration in the invasion front and the depth of tumor infiltration (p = 0.042). Conclusions: The immune response expressed by CD8+ T lymphocyte infiltration increases with the depth of tumor infiltration. An immune response expressed by a strong expression of CD8+ T lymphocytes may be an indicator of the absence of distant metastases. [ABSTRACT FROM AUTHOR]

The adenomatous polyposis coli (APC) gene is the chromatin-remodeling-related gene and a typical tumor suppressor. Patients with a high expression of programmed death-ligand 1 (PD-L1) or a high level of tumor mutational burden (TMB) may benefit from immunotherapy in endometrial cancer (EC). This study aimed to demonstrate the role of APC in the diagnosis and immunotherapy treatment of EC. We performed an integrative analysis of a commercial panel including 520 cancer-related genes on 99 tumors from an endometrial cancer cohort in China and DNA-seq data from The Cancer Genome Atlas (TCGA) to identify new gene mutations as endometrial cancer immunotherapy markers. We found that the significant mutant genes that correlated with the PD-L1 expression and TMB were related to the chromatin state and generated a discovery set having 12 mutated genes, including the APC gene, which was identified as a new marker for immunotherapy. Further analysis revealed that tumors with the APC mutation had high TMB, increased expression of PD-L1, and increased lymphocytic infiltration. Next, we verified that APC has an inactive mutation in EC, which may affect the immune response, including PD-L1 expression, microsatellite instability, and lymphocytic infiltrate. Furthermore, patients with the APC mutation had longer overall survival. Our study demonstrates that APC could play an important role in enhancing the response to endometrial cancer treatment, particularly immunotherapy.

Neutrophilic dermatosis of the hands (NDH) is a rare localized acral variant of Sweet syndrome. NDH predominantly involves the dorsal hands with characteristic dense dermal neutrophilic infiltrate with an upper dermal edema observed on histopathology. Unusual findings like palmar involvement and predominant lymphomononuclear dermal infiltration in our case with NDH, makes it an interesting read.

Background: Severity of lymphocytic infiltration to gastric mucosa is a good indicator for severity of H. Pylori gastritis Objectives: To evaluate the lymphocytic infiltration in the gastric mucosa associated with H. Pylori infection. Patients and Method(s): This study done on 50 cases with chronic gastritis and H.Pylori were detected by using geimsa stain with evaluation of degree of lymphocytic infiltration Results: H. Pylori infection was detected in 86% of cases with mild, moderate and severs infection in (34%, 42% and 10%) respectively. The lymphocytic infiltration found in 66% of cases with four levels (mild 24%, moderate 16%, sever without L.F 18%, sever with L.F 8%). There was statistically significant relation between severity of H.Pylori infection and severity of lymphocytic infiltration (p≤0.001). Conclusion: Lymphocytic infiltration is an important feature of H.Pylori gastritis

Copyright of Pamukkale Medical Journal is the property of Pamukkale Journal of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by deteriorated exocrine gland function with associated lymphocytic infiltration. However, there are few pathological studies on bronchial glands in SS. In this study, we aimed to clarify pathological features of bronchial glands in SS. Methods We retrospectively evaluated infiltration of lymphocytes in the bronchial glands incidentally collected by transbronchial lung cryobiopsy (TBLC), which were performed for the diagnosis of diffuse lung diseases. The degrees of lymphocyte infiltration in the bronchial glands were classified into four grades (grade 0–3). We compared the degrees of infiltration of SS with those of other diffuse lung diseases. Results TBLC for diagnosis of diffuse lung diseases were performed on 432 cases during the study period. The samples of 50 cases included bronchial glands. Of those, 20 cases were excluded due to insufficient size or influence of therapy. The remaining 30 cases included 17 of idiopathic interstitial pneumonias, 5 of chronic hypersensitivity pneumonia, 6 of connective tissue disease (SS; n = 4, systemic sclerosis; n = 1, dermatomyositis; n = 1) and 2 of other diseases. In SS, infiltration of lymphocytes was observed in all cases; grade 1 in one, grade 2 in one, and grade 3 in two cases. In contrast, 11 of 26 in other diseases showed no lymphocytes infiltration, with the remaining 15 of grade 1 infiltration. Grade 2 or more infiltration were found only in SS but not in other diseases. Conclusion Our results suggested that high-grade lymphocytic infiltration of bronchial glands is a distinct characteristics in SS.

Objective: To evaluate the detectability of herpes simplex virus type 1 and 2 (HSV-1, 2) antigens in the esophageal mucosa in esophageal cancer., Methods: A cross-sectional pilot study with a control group was conducted from December 2022 to May 2023. The patients were divided into two groups: the main group with verified esophageal cancer and the control group without esophageal cancer based on the histological report. Diagnosis using fibroesophagogastroscopy (FEGS), histological analysis, and indirect immunofluorescence reaction (iIFR) was accomplished according to indications at the outpatient center of the endoscopic department of the Multidisciplinary Medical Center, Astana. Descriptive statistics and nonparametric methods were used to analyze the data., Result: A total of 30 patients were recruited in the study, with 15 patients in the main group and 15 patients in the control group. HSV-1 and HSV-2 antigens were detected in the 13 cases (86.7%) during the study of biomaterial from patients with confirmed esophageal cancer in the main group and only in one case (6.8%) in the control group (95% CI 7.35 - 1126.9%, p=0.001). The presence of lymphocytic infiltration was detected in 13 cases (86.7%) in the main group and in 5 cases (33.3%) in the control group (95% CI 2.07 - 81.48%, p = 0.008). The process of keratinization was identified in HSV-1,2 antigens positive cases in the main group in 5 cases (35.7%) G1, in 5 cases (35.7%) G2, and in 3 cases (21.4 %) G3 (95% CI 1.66 - 656.23%, p=0.002)., Conclusion: Overall, the local activity of herpesvirus infection to a certain extent influences the malignant potential of tumor cells and the resistance of surrounding healthy tissues. A large-scale study is still needed to confirm these results. The present pilot study provided an overview of a possible method for detecting HSV-1,2 activity in malignant tissue from esophageal cancer.

Aim. In this paper, we aim to analyse our own clinical observation of a patient with CLIPPERS syndrome on the basis of available literature data. Materials and methods. The medical record of a patient treated at the Neurology Unit of the S.V. Ochapovsky Regional Clinical Hospital No. 1 (Kradnodarsy Krai) was investigated, along with available national and foreign literary sources. Results. The patient was diagnosed with autoimmune brainstem encephalitis (CLIPPERS syndrome) on the basis of the diagnostic CLIPPERS syndrome criteria modified and adapted by W. Tobin and co-authors in 2017. Among them are: 1) subacute development of symptoms for the pons and cerebellum lesions along with other signs of CNS damage (onset is characterised by diplopia and ataxia); 2) good response to glucocorticosteroid (GCS) therapy; 3) lack of involvement of the peripheral nervous system; 4) enhanced MRI lesions homogeneously accumulating contrast agents without a mass effect; 5) a significant decrease in the accumulation of contrast material during GCS therapy; 6) absence of myelin loss. Conclusion. Considering that the GCS therapy produces a rapid and significant effect, it is important to focus on early detection and treatment of this disease through the development of more accurate markers and evaluation criteria for its diagnosis.

Background. Lymphocytic infiltration of the pituitary is an unusual inflammatory disorder of the pituitary and indicated to be autoimmune in origin. Presentations depend on the site of involvement and degree of destruction of the cellular population of the pituitary and may range from an asymptomatic state to pan-hypopituitarism with or without mass effects. In the present study, we represent a rare case of lymphocytic infiltration of the pituitary gland who was diagnosed with such condition and the subsequent management. Case presentation. A 22-year-old male who was admitted with symptoms of increased thirst and excessive fatigue. Following a thorough physical, clinical, laboratory, biochemistry, and imaging examinations a timely diagnosis of lymphocytic infiltration of the pituitary was made without using the invasive procedure of pituitary biopsy. In light of the diagnosis prompt management with the mainstay of glucocorticoid was started along with replenishing the other deficient hormones. In this study we describe a rare case of lymphocytic infiltration of the pituitary discussing in terms of epidemiology, sign and symptoms, laboratory evaluation, imaging studies, histopathology, management, and the usual outcome. Conclusion. Lymphocytic infiltration of the pituitary gland can be diagnosed with the clinical presentation along with lab evaluation and imaging but without pituitary biopsy, which could help in an early and accurate diagnosis which is the basis for better management of the rare condition. [ABSTRACT FROM AUTHOR]

Neutrophilic dermatosis of the hands (NDH) is a rare localized acral variant of Sweet syndrome. NDH predominantly involves the dorsal hands with characteristic dense dermal neutrophilic infiltrate with an upper dermal edema observed on histopathology. Unusual findings like palmar involvement and predominant lymphomononuclear dermal infiltration in our case with NDH, makes it an interesting read. [ABSTRACT FROM AUTHOR]

Abstract Background We previously observed that T-bet+ tumor-infiltrating T lymphocytes (T-bet+ TILs) in primary breast tumors were associated with adverse clinicopathological features, yet favorable clinical outcome. We identified BRD4 (Bromodomain-Containing Protein 4), a member of the Bromodomain and Extra Terminal domain (BET) family, as a gene that distinguished T-bet+/high and T-bet−/low tumors. In clinical studies, BET inhibitors have been shown to suppress inflammation in various cancers, suggesting a potential link between BRD4 and immune infiltration in cancer. Hence, we examined the BRD4 expression and clinicopathological features of breast cancer. Methods The cohort consisted of a prospectively ascertained consecutive series of women with axillary node-negative breast cancer with long follow-up. Gene expression microarray data were used to detect mRNAs differentially expressed between T-bet+/high (n = 6) and T-bet−/low (n = 41) tumors. Tissue microarrays (TMAs) constructed from tumors of 612 women were used to quantify expression of BRD4 by immunohistochemistry, which was analyzed for its association with T-bet+ TILs, Jagged1, clinicopathological features, and disease-free survival. Results Microarray analysis indicated that BRD4 mRNA expression was up to 44-fold higher in T-bet+/high tumors compared to T-bet−/low tumors (p = 5.38E-05). Immunohistochemical expression of BRD4 in cancer cells was also shown to be associated with T-bet+ TILs (p = 0.0415) as well as with Jagged1 mRNA and protein expression (p = 0.0171, 0.0010 respectively). BRD4 expression correlated with larger tumor size (p = 0.0049), pre-menopausal status (p = 0.0018), and high Ki-67 proliferative index (p = 0.0009). Women with high tumoral BRD4 expression in the absence of T-bet+ TILs exhibited a significantly poorer outcome (log rank test p = 0.0165) relative to other subgroups. Conclusions The association of BRD4 expression with T-bet+ TILs, and T-bet+ TIL-dependent disease-free survival suggests a potential link between BRD4-mediated tumor development and tumor immune surveillance, possibly through BRD4’s regulation of Jagged1 signaling pathways. Further understanding BRD4’s role in different immune contexts may help to identify an appropriate subset of breast cancer patients who may benefit from BET inhibitors without the risk of diminishing the anti-tumoral immune activity.

CLIPPERS syndrome (Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids) is a recently described rare disease affecting the central nervous system. It is characterized by subacute development of symptoms of lesions predominantly in the brain stem and cerebellum, by specific magnetic resonance imaging (MRI) changes, perivascular lymphocytic infiltration in the brain substance and a good response to glucocorticoid (GC) therapy. The paper describes CLIPPERS syndrome in a patient who has been followed up in a clinic for 10 years. During this period, different variants of clinical diagnosis have been considered. The final diagnosis was made only when comparing the clinical course and manifestations of the disease, MRI data, as well as the reaction to GC therapy and its discontinuation. Literature data and diagnostic criteria of this disease are presented.

Background: The tumor microenvironment is highly heterogeneous, and it is understood to affect tumor progression and patient outcome. A number of studies have reported the prognostic significance of tumor-infiltrating lymphocytes and tumor budding in colorectal cancer (CRC). However, the significance of the intratumoral heterogeneity present in the spatial distribution of these features within the tumor immune microenvironment (TIME) has not been previously reported. Evaluating this intratumoral heterogeneity may aid the understanding of the TIME's effect on patient prognosis as well as identify novel aggressive phenotypes which can be further investigated as potential targets for new treatment. Methods: In this study, we propose and apply two spatial statistical methodologies for the evaluation of the intratumor heterogeneity present in the distribution of CD3 + and CD8 + lymphocytes and tumor buds (TB) in 232 Stage II CRC cases. Getis-Ord hotspot analysis was applied to quantify the cold and hotspots, defined as regions with a significantly low or high number of each feature of interest, respectively. A novel spatial heatmap methodology for the quantification of the cold and hotspots of each feature of interest, which took into account both the interpatient heterogeneity and the intratumor heterogeneity, was further developed. Results: Resultant data from each analysis, characterizing the spatial intratumor heterogeneity of lymphocytes and TBs were used for the development of two new highly prognostic risk models. Conclusions: Our results highlight the value of applying spatial statistics for the assessment of the intratumor heterogeneity. Both Getis-Ord hotspot and our proposed spatial heatmap analysis are broadly applicable across other tissue types as well as other features of interest. [ABSTRACT FROM AUTHOR]

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Neoadjuvant Chemotherapy (NACT) followed by Interval Debulking Surgery (IDS) is an accepted frontline treatment in patients with advanced Epithelial Ovarian Cancer (EOC). Histopathologic assessment of tumor post NACT may provide a surrogate for response to treatment. The present study aims to characterize the pathological response and to examine its prognostic significance in these patients. Medical records of women with EOC treated in our institution from 2011 to 2016 were retrospectively identified. IDS specimens were reviewed by study pathologist and Chemotherapy Response Score (CRS), lymphocytic infiltration, necrosis and mitosis were assessed. 55 patients with EOC treated with NACT were identified and 48 had complete clinical and pathological data. Median age was 63 years. CRS assessed at omentum predicted PFS when adjusted for age, stage, debulking status (complete, optimal, suboptimal) and post IDS bevacizumab administration (mPFS CRS 1 vs 2 vs 3: 10.3–14–18.7 months 95% CI [7.4–15.7], [12.2–22.9], [13.5–31.3]). Presence of lymphocytic infiltration was associated with improved OS (log-rank test P = 0.015). Post IDS bevacizumab was associated with shorter PFS in patients with lymphocytic infiltration. BRCA status was known for 25 patients and presence of BRCA1/2 mutations was strongly correlated with lymphocytic infiltration (P = 0.011) but not CRS omentum (P = 0.926). Our study confirms the predictive value of CRS in EOC patients treated with NACT and IDS, but also demonstrates the prognostic significance of lymphocytic infiltration as well as its possible interaction with bevacizumab treatment. • Chemotherapy Response Score is prognostic. • Lymphocytic infiltration in pretreatment biopsies is prognostic. • Bevacizumab administration may adversely affect the survival of patients with lymphocytic infiltration. [ABSTRACT FROM AUTHOR]

Introduction/Objective. We examine the prognostic significance and association between lymphocytic infiltration and papillary thyroid carcinoma. This manuscript aims to establish whether the presence of lymphocytic infiltration in the classical type of papillary thyroid carcinoma is a favorable prognostic factor for survival. Methods. This is a retrospective study of patients treated for papillary thyroid carcinoma at the Clinical Centre of Montenegro over a period of seven years (2010–2017). A total of 105 patients aged 12 to 84 years were included in the study, of which 74% showed concomitant histological evidence of lymphocytic infiltration. The patients were divided into two groups – one with lymphocytic infiltration and the other without it. Anti-CD3 and anti-CD20 antibodies were used to identify T and B lymphocytes. The prognostic outcome was assessed using the Kaplan–Meier survival plots. Results. The cohort with lymphocytic infiltration revealed a lower frequency of extrathyroidal invasion (p < 0.0001), nodal metastases (p < 0.0001), and the absence of distant metastases, compared with those without lymphocytic infiltration. Chronic lymphocytic thyroiditis is a favorable prognostic factor for survival in our examined group (p < 0.0001). Conclusion. The present study shows that immune reaction involving lymphocytic infiltration plays a role in extrathyroidal tumor growth and development of nodal and distant metastases in patients with papillary thyroid cancer. The presence of lymphocytic infiltration is a favorable factor for survival in the classical form of papillary thyroid carcinoma.

The etiopathologies behind autoimmune thyroid diseases (AITDs) unravel misbehavior of immune components leading to the corruption of immune homeostasis where thyroid autoantigens turn foe to the self. In AITDs lymphocytic infiltration in the thyroid shows up a deranged immune system charging the follicular cells of the thyroid gland (thyrocytes) leading to the condition of either hyperthyroidism or hypothyroidism. The inflammation in AITDs consistently associate with ER function due to which disturbances in the ER protein homeostasis leads to unfolded protein response (UPR) that promotes pathogenesis of autoimmunity. The roles of ER stress in the instantaneous downregulation of MHC class I molecules on thyrocytes and the relevance of IFN γ in the pathogenesis of AITD has been well-documented. Thyroglobulin being the major target of autoantibodies in most of the AITDs is because of its unusual processing in the ER. Autoimmune disorders display a conglomeration of ER stress-induced UPR activated molecules. Several epidemiological data highlight the preponderance of AITDs in women as well as its concurrence with breast cancer. Both being an active glandular system displaying endocrine activity, thyroid as well as breast tissue show various commonalities in the expression pattern of heterogenous molecules that not only participate in the normal functioning but at the same time share the blame during disease establishment. Studies on the development and progression of breast carcinoma display a deranged and uncontrolled immune response, which is meticulously exploited during tumor metastasis. The molecular crosstalks between AITDs and breast tumor microenvironment rely on active participation of immune cells. The induction of ER stress by Tunicamycin advocates to provide a model for cancer therapy by intervening glycosylation. Therefore, this review attempts to showcase the molecules that are involved in feeding up the relationship between breast carcinoma and AITDs.

Morphology of the Meckel's diverticulum (MD) of broiler chicken was investigated using gross anatomical, histological and transmission electron microscopy techniques. Forty fertile eggs and 100 chicks of Marshall broiler chicken were used for the study. Samples were collected from 6 randomly selected embryos or chicks on embryonic days 14, 17 and 19, and post-hatch days 1, 3, 5, 7, 14, 21, 28, 35, 42 and 56. The results showed that the mean lengths of the small intestine from the gizzard to the MD and from the MD to the ileocecal junction increased steadily with age. On embryonic days 14, 17 and 19, the poorly differentiated tunics of the MD were composed of lamina epithelialis mucosae and indistinct lamina propria mucosae as well as submucosal areas. The tunica muscularis exhibited loose islands of nascent smooth muscle fibres. Whereas on post-hatch day 1, the lamina epithelialis mucosae showed scanty microvilli and enterocytes with large cytoplasmic vacuoles, the MD of 3-day-old post-hatch chicks contained lymphatic tissues in the lamina propria mucosae. On post-hatch day 35, the lamina epithelialis mucosae demonstrated the presence of apoptotic cells while numerous lymphocytes at various stages of differentiation were observed within the lamina propria mucosae and tunica submucosa. In conclusion, the present study has provided clear structural evidence which shows that intense cellular proliferation occurs in the MD of broiler chicken between embryonic days 14 and 19. This organ may play significant roles in immunological surveillance of the gut, and such functions may peak on post-hatch day 35. [ABSTRACT FROM AUTHOR]

Conjunctival nevi in young individuals can correspond to the entity named Inflammatory Juvenile Conjunctival Nevus (IJCN), presenting clinically as a rapid growth lesion, and showing at the histopathological study an inflammatory infiltrate surrounding the lesion. All these findings can suggest a diagnosis of malignancy. Due to a case of IJCN diagnosed in our Pathology department, we realized that this entity is rarely reported in the literature and histopathological diagnostic criteria are not well defined. The aim of our study is to compare the histopathological characteristics of conjunctival nevi in patients aged thirty years or less to those in patients above 30 years, looking for the findings described in IJCN. All the excisional specimens of resected conjunctival nevus in a tertiary hospital from 2000 to 2018 were retrieved from the Pathology department archives. Demographic data were recorded, and histopathological variables (histological type of nevus, lymphocytic infiltration, eosinophilic infiltration, presence of lymphoid follicles, stromal nevomelanocytic component, intraepithelial nevomelanocytic component, epithelial inclusions, quantity of goblet cells in epithelial inclusions, cellular atypia, mitoses and maturation of the lesion) were evaluated by three independent observers. Statistical analysis was performed comparing the two age groups. The study determined a significant predominance of the lymphocytic and eosinophilic infiltration in the group of patients aged thirty years or less respect to the elderly group. The percentage of stromal component of the lesion is larger in patients over thirty years compared to the younger group. There was no correlation between epithelial inclusions, maturation or cytological atypia and age groups. We found some histopathological differences in conjunctival nevi related to young age, some of them coincident with the ones described in IJCN, which histopathologically could lead to a misleading diagnosis. However, we did not find significant differences related to age in many of the described histopathological findings described in IJCN. Larger series with a greater number of cases would be of interest to characterize more precisely this lesion. [ABSTRACT FROM AUTHOR]

The etiopathologies behind autoimmune thyroid diseases (AITDs) unravel misbehavior of immune components leading to the corruption of immune homeostasis where thyroid autoantigens turn foe to the self. In AITDs lymphocytic infiltration in the thyroid shows up a deranged immune system charging the follicular cells of the thyroid gland (thyrocytes) leading to the condition of either hyperthyroidism or hypothyroidism. The inflammation in AITDs consistently associate with ER function due to which disturbances in the ER protein homeostasis leads to unfolded protein response (UPR) that promotes pathogenesis of autoimmunity. The roles of ER stress in the instantaneous downregulation of MHC class I molecules on thyrocytes and the relevance of IFN γ in the pathogenesis of AITD has been well-documented. Thyroglobulin being the major target of autoantibodies in most of the AITDs is because of its unusual processing in the ER. Autoimmune disorders display a conglomeration of ER stress-induced UPR activated molecules. Several epidemiological data highlight the preponderance of AITDs in women as well as its concurrence with breast cancer. Both being an active glandular system displaying endocrine activity, thyroid as well as breast tissue show various commonalities in the expression pattern of heterogenous molecules that not only participate in the normal functioning but at the same time share the blame during disease establishment. Studies on the development and progression of breast carcinoma display a deranged and uncontrolled immune response, which is meticulously exploited during tumor metastasis. The molecular crosstalks between AITDs and breast tumor microenvironment rely on active participation of immune cells. The induction of ER stress by Tunicamycin advocates to provide a model for cancer therapy by intervening glycosylation. Therefore, this review attempts to showcase the molecules that are involved in feeding up the relationship between breast carcinoma and AITDs. [ABSTRACT FROM AUTHOR]

Background: We previously observed that T-bet+ tumor-infiltrating T lymphocytes (T-bet+ TILs) in primary breast tumors were associated with adverse clinicopathological features, yet favorable clinical outcome. We identified BRD4 (Bromodomain-Containing Protein 4), a member of the  Bromodomain and Extra Terminal domain (BET) family, as a gene that distinguished T-bet+/high and T-bet-/low tumors. In clinical studies, BET inhibitors have been shown to suppress inflammation in various cancers, suggesting a potential link between BRD4 and immune infiltration in cancer. Hence, we examined the BRD4 expression and clinicopathological features of breast cancer.Methods: The cohort consisted of a prospectively ascertained consecutive series of women with axillary node-negative breast cancer with long follow-up. Gene expression microarray data were used to detect mRNAs differentially expressed between T-bet+/high (n = 6) and T-bet-/low (n = 41) tumors. Tissue microarrays (TMAs) constructed from tumors of 612 women were used to quantify expression of BRD4 by immunohistochemistry, which was analyzed for its association with T-bet+ TILs, Jagged1, clinicopathological features, and disease-free survival.Results: Microarray analysis indicated that BRD4 mRNA expression was up to 44-fold higher in T-bet+/high tumors compared to T-bet-/low tumors (p = 5.38E-05). Immunohistochemical expression of BRD4 in cancer cells was also shown to be associated with T-bet+ TILs (p = 0.0415) as well as with Jagged1 mRNA and protein expression (p = 0.0171, 0.0010 respectively). BRD4 expression correlated with larger tumor size (p = 0.0049), pre-menopausal status (p = 0.0018), and high Ki-67 proliferative index (p = 0.0009). Women with high tumoral BRD4 expression in the absence of T-bet+ TILs exhibited a significantly poorer outcome (log rank test p = 0.0165) relative to other subgroups.Conclusions: The association of BRD4 expression with T-bet+ TILs, and T-bet+ TIL-dependent disease-free survival suggests a potential link between BRD4-mediated tumor development and tumor immune surveillance, possibly through BRD4's regulation of Jagged1 signaling pathways. Further understanding BRD4's role in different immune contexts may help to identify an appropriate subset of breast cancer patients who may benefit from BET inhibitors without the risk of diminishing the anti-tumoral immune activity. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is an immunosuppressive malignancy characterized by tumor-driven immune-system abnormalities that contribute to disease progression. For patients with surgically resectable HNSCC, treatment is often curative surgery followed by irradiation or chemoradiation in high-risk settings to reduce the risk of recurrence. Poor survival and considerable morbidity of current treatments suggest the need for new therapeutic modalities that can improve outcomes. Defects in antitumor immunity of HNSCC patients include suppressed dendritic cell (DC) maturation, deficient antigen-presenting cell function, compromised natural killer (NK)-cell cytotoxicity, increased apoptosis of activated T lymphocytes, and impaired immune-cell migration to tumor sites. Strategies for relieving immunosuppression and restoring antitumor immune functions could benefit HNSCC patients. IRX-2 is a primary cell-derived biologic consisting of physiologic levels of T-helper type 1 cytokines produced by stimulating peripheral blood mononuclear cells of normal donors with phytohemagglutinin. The primary active components in IRX-2 are IL2, IL1β, IFNγ, and TNFα. In vitro, IRX-2 acts on multiple immune-system cell types, including DCs, T cells, and NK cells, to overcome tumor-mediated immunosuppression. In clinical settings, IRX-2 is administered as part of a 21-day neoadjuvant regimen, which includes additional pharmacologic agents (low-dose cyclophosphamide, indomethacin, and zinc) to promote anticancer immunoresponses. In a Phase IIA trial in 27 patients with surgically resectable, previously untreated HNSCC, neoadjuvant IRX-2 increased infiltration of T cells, B cells, and DCs into tumors and was associated with radiological reductions in tumor size. Event-free survival was 64% at 2 years, and overall 5-year survival was 65%. Follow-up and data analysis are under way in the multicenter, randomized, Phase IIB INSPIRE trial evaluating the IRX-2 regimen as a stand-alone therapy for activating the immune system to recognize and attack tumors. [ABSTRACT FROM AUTHOR]