Pub Date : 2022-01-01DOI: 10.31088/cem2023.12.2.25-35
M. Zavyalova, D. Loos, D. S. Pismenny, A. A. Durova, E. S. Andryukhova, E. Rodionov, S. Miller, S. Tuzikov, L. Tashireva, O. Pankova, V. Perelmuter
Introduction. To date, the molecular mechanisms underlying the development of STAS remain poorly understood. The development of STAS – a marker of an unfavorable outcome of lung cancer – is likely to be associated with markers of a high risk of hematogenous metastasis and recurrence, i.e., changes in the bronchial epithelium.The paper aimed to study the features of STAS in patients with different morphological changes in the bronchial epithelium. Materials and methods. We studied surgical material from 90 patients with non-small cell lung cancer who received combined treatment in the thoracoabdominal department of the Research Institute of Oncology of the Tomsk National Research Medical Center between 2009 and 2017. Case histories and outpatient cards of patients were analyzed. We determined the prevalence of the disease according to the international classification using the TNM staging system (2017). We used the standard method to post the material and manufacture histological preparations. The 2015 WHO classification was used to determine the histological type of cancer. The study included only cases with non-small cell lung carcinoma, namely squamous cell carcinoma (n=50) or adenocarcinoma (n=40). In the lymph nodes, we assessed the presence of metastatic lesions and counted the number of lymph nodes with metastases. In the bronchial mucosa located 3–4 cm from the border of the tumor, we assessed the presence of changes in the bronchial epithelium. The information about the presence, timing, and location of hematogenous metastases and relapses was taken into account. We used descriptive statistics; the results were discussed with the statistically significant difference at p<0.05. Results. We identified a number of patterns that could complement the understanding of SPAS pathogenesis, a form of tumor progression relevant for lung cancer. Conclusion. We propose to consider the detection of STAS as an unfavorable prognostic sign associated with the risk of locoregional metastasis. Keywords: STAS, non-small cell lung cancer, regenerative hyperplasia of the bronchial epithelium, metaplasia of the bronchial epithelium, metastasis
{"title":"Features of tumor spread through the air spaces in patients with non-small cell lung carcinoma","authors":"M. Zavyalova, D. Loos, D. S. Pismenny, A. A. Durova, E. S. Andryukhova, E. Rodionov, S. Miller, S. Tuzikov, L. Tashireva, O. Pankova, V. Perelmuter","doi":"10.31088/cem2023.12.2.25-35","DOIUrl":"https://doi.org/10.31088/cem2023.12.2.25-35","url":null,"abstract":"Introduction. To date, the molecular mechanisms underlying the development of STAS remain poorly understood. The development of STAS – a marker of an unfavorable outcome of lung cancer – is likely to be associated with markers of a high risk of hematogenous metastasis and recurrence, i.e., changes in the bronchial epithelium.The paper aimed to study the features of STAS in patients with different morphological changes in the bronchial epithelium. Materials and methods. We studied surgical material from 90 patients with non-small cell lung cancer who received combined treatment in the thoracoabdominal department of the Research Institute of Oncology of the Tomsk National Research Medical Center between 2009 and 2017. Case histories and outpatient cards of patients were analyzed. We determined the prevalence of the disease according to the international classification using the TNM staging system (2017). We used the standard method to post the material and manufacture histological preparations. The 2015 WHO classification was used to determine the histological type of cancer. The study included only cases with non-small cell lung carcinoma, namely squamous cell carcinoma (n=50) or adenocarcinoma (n=40). In the lymph nodes, we assessed the presence of metastatic lesions and counted the number of lymph nodes with metastases. In the bronchial mucosa located 3–4 cm from the border of the tumor, we assessed the presence of changes in the bronchial epithelium. The information about the presence, timing, and location of hematogenous metastases and relapses was taken into account. We used descriptive statistics; the results were discussed with the statistically significant difference at p<0.05. Results. We identified a number of patterns that could complement the understanding of SPAS pathogenesis, a form of tumor progression relevant for lung cancer. Conclusion. We propose to consider the detection of STAS as an unfavorable prognostic sign associated with the risk of locoregional metastasis. Keywords: STAS, non-small cell lung cancer, regenerative hyperplasia of the bronchial epithelium, metaplasia of the bronchial epithelium, metastasis","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69281267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.31088/cem2022.11.1.43-49
P. Pigarevsky, S. Maltseva, V. Snegova, N. G. Davydova, O. G. Yakovleva
Introduction. In the pathogenesis of atherosclerosis, a change in the content of different proteins in S100 protein family may play an important role in the formation of atherosclerotic lesions in the vascular wall. The aim was to study the content of mononuclear cells expressing protein S100A8 in different types of atherosclerotic lesions secondary to the development of the inflammatory process in the vascular wall during atherogenesis in humans. Materials and methods. Immunohistochemical and morphometric studies were performed on autopsy material (18 cases) obtained from patients who died from acute cardiovascular insufficiency of atherosclerotic etiology. We detected the expression of S100A8 protein in the aortic segments (from the arc, thoracic and abdominal regions), coronary arteries, and arteries of the circle of Willis (40 tissue samples) using a highly sensitive two-stage streptavidin-biotin method. Comparative analysis was subjected to normal areas of arteries, lipid stain, and unstable and stable atherosclerotic plaques. We performed a statistical analysis with the computer program Statistica Version 10. The significance of the differences between the samples studied was determined by the Student’s T-criterion. Results. Intracellular localization of S100A8 protein was found in the intima of unstable atherosclerotic lesions. Its expression was mainly concentrated in the cytoplasm of macrophages. Intracellular production of S100A8 was minimal or absent in normal areas of aorta intima, coronary arteries, a. basilaris, and in the cap of stable atherosclerotic plaques. We detected numerous inflammatory mononuclear cell infiltrates in the areas of the vascular wall with S100A8 expression. According to the morphometry, their content in the intima of unstable plaques significantly exceeded the similar rate in the intima of normal areas of arteries and stable lesions. Conclusion. We hypothesize that protein S100A8 may contribute to the activation of immune-inflammatory reactions in the vascular wall, which are the basis for the formation of unstable progressive atherosclerotic lesions leading to the development of acute coronary syndrome. Further research may provide more evidence to support that S100A8 proteins are a promising drug target in the prevention and therapy of atherosclerosis. Keywords: atherogenesis, S100A8 protein, unstable atherosclerotic plaque
介绍。在动脉粥样硬化的发病过程中,S100蛋白家族中不同蛋白含量的变化可能对血管壁动脉粥样硬化病变的形成起重要作用。目的是研究人类动脉粥样硬化过程中继发于血管壁炎症过程的不同类型动脉粥样硬化病变中表达S100A8蛋白的单个核细胞的含量。材料和方法。对18例因动脉粥样硬化致急性心血管功能不全死亡患者的尸检材料进行了免疫组织化学和形态计量学研究。我们使用高灵敏度的两阶段链霉亲和素-生物素法检测了S100A8蛋白在主动脉段(来自弧区、胸区和腹区)、冠状动脉和威利斯环动脉(40个组织样本)中的表达。对正常动脉区域、脂质染色、不稳定和稳定的动脉粥样硬化斑块进行比较分析。我们用计算机程序Statistica Version 10进行了统计分析。研究样本之间差异的显著性由学生t标准确定。结果。在不稳定动脉粥样硬化病变的内膜中发现了S100A8蛋白的细胞内定位。其表达主要集中在巨噬细胞的细胞质中。在主动脉内膜、冠状动脉、基底动脉的正常区域和稳定的动脉粥样硬化斑块中,细胞内S100A8的产生很少或不存在。我们在S100A8表达的血管壁区域检测到大量炎性单核细胞浸润。从形态学上看,它们在不稳定斑块内膜中的含量明显超过动脉正常区域和稳定病变内膜的相似率。结论。我们假设S100A8蛋白可能促进了血管壁免疫炎症反应的激活,这是不稳定进行性动脉粥样硬化病变形成的基础,导致急性冠状动脉综合征的发展。进一步的研究可能会提供更多的证据来支持S100A8蛋白是预防和治疗动脉粥样硬化的一个有希望的药物靶点。关键词:动脉粥样硬化,S100A8蛋白,不稳定动脉粥样硬化斑块
{"title":"Protein S100A8 in atherosclerotic lesions in humans","authors":"P. Pigarevsky, S. Maltseva, V. Snegova, N. G. Davydova, O. G. Yakovleva","doi":"10.31088/cem2022.11.1.43-49","DOIUrl":"https://doi.org/10.31088/cem2022.11.1.43-49","url":null,"abstract":"Introduction. In the pathogenesis of atherosclerosis, a change in the content of different proteins in S100 protein family may play an important role in the formation of atherosclerotic lesions in the vascular wall. The aim was to study the content of mononuclear cells expressing protein S100A8 in different types of atherosclerotic lesions secondary to the development of the inflammatory process in the vascular wall during atherogenesis in humans. Materials and methods. Immunohistochemical and morphometric studies were performed on autopsy material (18 cases) obtained from patients who died from acute cardiovascular insufficiency of atherosclerotic etiology. We detected the expression of S100A8 protein in the aortic segments (from the arc, thoracic and abdominal regions), coronary arteries, and arteries of the circle of Willis (40 tissue samples) using a highly sensitive two-stage streptavidin-biotin method. Comparative analysis was subjected to normal areas of arteries, lipid stain, and unstable and stable atherosclerotic plaques. We performed a statistical analysis with the computer program Statistica Version 10. The significance of the differences between the samples studied was determined by the Student’s T-criterion. Results. Intracellular localization of S100A8 protein was found in the intima of unstable atherosclerotic lesions. Its expression was mainly concentrated in the cytoplasm of macrophages. Intracellular production of S100A8 was minimal or absent in normal areas of aorta intima, coronary arteries, a. basilaris, and in the cap of stable atherosclerotic plaques. We detected numerous inflammatory mononuclear cell infiltrates in the areas of the vascular wall with S100A8 expression. According to the morphometry, their content in the intima of unstable plaques significantly exceeded the similar rate in the intima of normal areas of arteries and stable lesions. Conclusion. We hypothesize that protein S100A8 may contribute to the activation of immune-inflammatory reactions in the vascular wall, which are the basis for the formation of unstable progressive atherosclerotic lesions leading to the development of acute coronary syndrome. Further research may provide more evidence to support that S100A8 proteins are a promising drug target in the prevention and therapy of atherosclerosis. Keywords: atherogenesis, S100A8 protein, unstable atherosclerotic plaque","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69279761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.31088/cem2022.11.2.54-62
A. Epishkina, A. Avdalyan, E. Grebenkin, D. Kobyakov, D. Protsenko, O. Zayratyants
Introduction. Non-small cell lung cancer (NSCLC), including squamous cell carcinoma, accounts for 80% of all lung cancers. Anti-angiogenic drugs are currently available for NSCLC treatment. However, there are no predictive biomarkers for selecting patients who could benefit from this therapy. The aim of the study was to assess the correlation between the density of the tumor vascular microenvironment and the tumor size, as well as between the density of tumor lymphatic vessels and the presence or absence of metastases in the ipsilateral peribronchial lymph nodes. Materials and methods. Patients with a morphologically verified diagnosis of squamous cell lung carcinoma were divided into 2 groups depending on the stage of cancer: group 1 (stage I, n=15) and group 2 (stage II, n=15). We performed a morphometric study of histological slides stained with hematoxylin and eosin and antibodies to CD34 and Podoplanin (specific and sensitive markers to blood and lymphatic vessels, re-spectively) with immunohistochemical methods. Vascular density was assessed according to the Chalkley method. We quantitatively evaluated the density of blood vessels in absolute numbers on a 0.73-mm² area with a magnification of ×200 (three fields of view were evaluated with subsequent calculation of the mean blood vessels density). Results. The median of vascular density of the microvasculature was 9.67 (8.67; 10.33) and 10.33 (9.67; 11.67) in the intratumoral zone in group 1 and group 2, respectively. In the peritumoral zone, it was 12 (11.33; 12.67) for group 1 and 16.33 (15.67; 19.67) for group 2. The median density of lymphatic vessels in group 1 and group 2 in the intratumoral zone amounted to 1.5 (1; 2) and 2 (1.67; 3.75), respectively; whereas in the peritumoral zone, this parameter was 2 (1.92; 2.75) and 3.33 (2.67; 4) for groups 1 and 2, respectively. We found a correlation between tumor size and vascular density of the microvasculature in the peritumoral zone (p<0.05) and between the density of lymphatic vessels in the peritumoral zone and the presence of metastases in the peribronchial lymph nodes (p<0.05). Conclusion. Features of the vascular microenvironment of the tumor contribute to the progression of squa-mous cell carcinoma of the lung. Keywords: squamous cell lung cancer, tumor vascular microenvironment, tumor vascular density
{"title":"Morphological assessment of the vascular microenvironment of squamous cell carcinomas of lung","authors":"A. Epishkina, A. Avdalyan, E. Grebenkin, D. Kobyakov, D. Protsenko, O. Zayratyants","doi":"10.31088/cem2022.11.2.54-62","DOIUrl":"https://doi.org/10.31088/cem2022.11.2.54-62","url":null,"abstract":"Introduction. Non-small cell lung cancer (NSCLC), including squamous cell carcinoma, accounts for 80% of all lung cancers. Anti-angiogenic drugs are currently available for NSCLC treatment. However, there are no predictive biomarkers for selecting patients who could benefit from this therapy. The aim of the study was to assess the correlation between the density of the tumor vascular microenvironment and the tumor size, as well as between the density of tumor lymphatic vessels and the presence or absence of metastases in the ipsilateral peribronchial lymph nodes. Materials and methods. Patients with a morphologically verified diagnosis of squamous cell lung carcinoma were divided into 2 groups depending on the stage of cancer: group 1 (stage I, n=15) and group 2 (stage II, n=15). We performed a morphometric study of histological slides stained with hematoxylin and eosin and antibodies to CD34 and Podoplanin (specific and sensitive markers to blood and lymphatic vessels, re-spectively) with immunohistochemical methods. Vascular density was assessed according to the Chalkley method. We quantitatively evaluated the density of blood vessels in absolute numbers on a 0.73-mm² area with a magnification of ×200 (three fields of view were evaluated with subsequent calculation of the mean blood vessels density). Results. The median of vascular density of the microvasculature was 9.67 (8.67; 10.33) and 10.33 (9.67; 11.67) in the intratumoral zone in group 1 and group 2, respectively. In the peritumoral zone, it was 12 (11.33; 12.67) for group 1 and 16.33 (15.67; 19.67) for group 2. The median density of lymphatic vessels in group 1 and group 2 in the intratumoral zone amounted to 1.5 (1; 2) and 2 (1.67; 3.75), respectively; whereas in the peritumoral zone, this parameter was 2 (1.92; 2.75) and 3.33 (2.67; 4) for groups 1 and 2, respectively. We found a correlation between tumor size and vascular density of the microvasculature in the peritumoral zone (p<0.05) and between the density of lymphatic vessels in the peritumoral zone and the presence of metastases in the peribronchial lymph nodes (p<0.05). Conclusion. Features of the vascular microenvironment of the tumor contribute to the progression of squa-mous cell carcinoma of the lung. Keywords: squamous cell lung cancer, tumor vascular microenvironment, tumor vascular density","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69280439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.31088/cem2022.11.4.48-52
T. Gaydina, O. Patsap, A. Dvornikov
Despite the prevalence of melanocytic skin nevi (MSN) in the population, the management of patients especially with multiple melanocytic nevi remains ambiguous. According to some studies, after removal, the frequency of recurrence of MSN ranges from 11.7% to 20% after shave biopsy and destructive physical methods, respectively. Recurrent melanocytic skin nevus is a histological mimic of skin melanoma and requires careful diagnosis. The article presents a clinical case of recurrent melanocytic nevus that was first diagnosed with an optical device Handyscope (FotoFinder; Germany) and Handyscope3 app based on artificial intelligence (AI) and then confirmed by subsequent histological examination. Since it is impossible to predict which MSN will relapse and considering that the recurrence of melanocytic nevi does not always correlate with amount of lesion excision and a surgeon’s experience, it is necessary to develop clear criteria on the feasibility and removal method of melanocytic nevi, including the use of AI. All removals of melanocytic nevi should be carried out only with histological examination with further mandatory long-term follow-up. Keywords: recurrent melanocytic skin nevus, melanoma of the skin, melanocytic skin nevus
{"title":"Features of clinical and histological diagnosis of recurrent melanocytic nevus","authors":"T. Gaydina, O. Patsap, A. Dvornikov","doi":"10.31088/cem2022.11.4.48-52","DOIUrl":"https://doi.org/10.31088/cem2022.11.4.48-52","url":null,"abstract":"Despite the prevalence of melanocytic skin nevi (MSN) in the population, the management of patients especially with multiple melanocytic nevi remains ambiguous. According to some studies, after removal, the frequency of recurrence of MSN ranges from 11.7% to 20% after shave biopsy and destructive physical methods, respectively. Recurrent melanocytic skin nevus is a histological mimic of skin melanoma and requires careful diagnosis. The article presents a clinical case of recurrent melanocytic nevus that was first diagnosed with an optical device Handyscope (FotoFinder; Germany) and Handyscope3 app based on artificial intelligence (AI) and then confirmed by subsequent histological examination. Since it is impossible to predict which MSN will relapse and considering that the recurrence of melanocytic nevi does not always correlate with amount of lesion excision and a surgeon’s experience, it is necessary to develop clear criteria on the feasibility and removal method of melanocytic nevi, including the use of AI. All removals of melanocytic nevi should be carried out only with histological examination with further mandatory long-term follow-up. Keywords: recurrent melanocytic skin nevus, melanoma of the skin, melanocytic skin nevus","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69280692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.31088/cem2022.11.4.53-58
N. V. Motina, N. Veselovskaya, G. Kostyuchenko, A. Ott, V.Y. Gervald, Y. Motin
We present a clinical and morphological case study of a delayed LAMP2-cardiomyopathy (Danon disease) in a 44-year-old woman. LAMP2-cardiomyopathy is caused by impaired autophagy processes due to lysosome-associated membrane protein-2 (LAMP-2) deficiency in cardiomyocytes. This is a rare and diagnostically challenging condition inherited in an X-linked dominant pattern. A medical triad includes myocardial damage with hypertrophic LAMP2-cardiomyopathy, intellectual disability, and skeletal myopa-thy, the first one being the most significant prognostic factor and the main cause of death in these patients. However, autophagy disturbance and lysosomal glycogen accumulation in cardiomyocytes often remain unrecognized as the cause of hypertrophic cardiomyopathy. The report briefly describes disease etiology and epidemiology and outlines the clinical findings of the morphological study focusing on intravital ultra-structural features of structural changes in the myocardium. We provide data from the patient’s history, the results of laboratory and imaging studies, as well as endomyocardial biopsy examination at the light-optical and electron microscopic levels. Keywords: Danon disease, hypertrophic cardiomyopathy, LAMP2, electron microscopy
{"title":"Morphological features of the myocardium in LAMP2-cardiomyopathy","authors":"N. V. Motina, N. Veselovskaya, G. Kostyuchenko, A. Ott, V.Y. Gervald, Y. Motin","doi":"10.31088/cem2022.11.4.53-58","DOIUrl":"https://doi.org/10.31088/cem2022.11.4.53-58","url":null,"abstract":"We present a clinical and morphological case study of a delayed LAMP2-cardiomyopathy (Danon disease) in a 44-year-old woman. LAMP2-cardiomyopathy is caused by impaired autophagy processes due to lysosome-associated membrane protein-2 (LAMP-2) deficiency in cardiomyocytes. This is a rare and diagnostically challenging condition inherited in an X-linked dominant pattern. A medical triad includes myocardial damage with hypertrophic LAMP2-cardiomyopathy, intellectual disability, and skeletal myopa-thy, the first one being the most significant prognostic factor and the main cause of death in these patients. However, autophagy disturbance and lysosomal glycogen accumulation in cardiomyocytes often remain unrecognized as the cause of hypertrophic cardiomyopathy. The report briefly describes disease etiology and epidemiology and outlines the clinical findings of the morphological study focusing on intravital ultra-structural features of structural changes in the myocardium. We provide data from the patient’s history, the results of laboratory and imaging studies, as well as endomyocardial biopsy examination at the light-optical and electron microscopic levels. Keywords: Danon disease, hypertrophic cardiomyopathy, LAMP2, electron microscopy","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69280717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.31088/cem2023.12.2.54-60
A. Sherstnev, A. Kovrigina, L. Gorenkova
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
{"title":"Pathomorphological diagnosis of primary cutaneous CD4-positive small/medium T-cell lymphoproliferative disorder: a 28-case series","authors":"A. Sherstnev, A. Kovrigina, L. Gorenkova","doi":"10.31088/cem2023.12.2.54-60","DOIUrl":"https://doi.org/10.31088/cem2023.12.2.54-60","url":null,"abstract":"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","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69281348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.31088/cem2022.11.1.33-42
V. Pechnikova, A. Pshikhachev, L. Mikhaleva
Introduction. Bladder cancer (BC) is a significant public health problem due to its high likelihood of relapse and local or metastatic progression, which requires big government funding. The study of the urothelial precancerous lesions contributes to the earlier disease detection and influences the management strategy. However, experts argue on how to interpret pathological processes of the urothelium, therefore, the purpose of our study was to evaluate clinical and morphological features of inflammatory, precancerous, and cancerous lesions of the urothelium. Materials and methods. The study included 120 patients (77 men and 43 women) with inflammatory, pre-cancerous, and cancerous lesions of the urothelium. The patients were divided into 4 subgroups: subgroup I included 11 patients with reactive atypia of the urothelium; subgroup II involved 24 patients with urothelial dysplasia; subgroup III consisted of 51 patients with non–muscle-invasive BC (NMIBC); and subgroup IV included 34 patients with muscle-invasive BC (MIBC). We assessed clinically gender, age, size, lesion location, singleness and multiplicity of lesions, and the presence of blood in the urine. We also performed pathological assessment for subgroups III and IV: we studied the level of tumor invasion and the tumor grade. For statistical processing of the data, we used IBM SPSS Statistics (version 23) for Windows. Results. The study revealed tumor lesions to be more common in men than in women. The size of urothelial dysplasia in women was significantly greater than in men (U=26; p=0.019). In subgroup III (NMIBC), multiple lesions were more common with increasing age (U=155.5; p=0.048). In subgroup IV (MIBC), younger patients were found to have less differentiated tumors. Conclusion. This study demonstrated the clinical and morphological features of patients with inflammatory, precancerous, and cancerous lesions of the bladder. Keywords: bladder cancer, muscle non-invasive bladder cancer, muscle invasive bladder cancer, urothelial dysplasia, reactive atypia, oncology, pathology
{"title":"Clinical and morphological features of inflammatory, precancerous, and cancerous lesions of the urothelium","authors":"V. Pechnikova, A. Pshikhachev, L. Mikhaleva","doi":"10.31088/cem2022.11.1.33-42","DOIUrl":"https://doi.org/10.31088/cem2022.11.1.33-42","url":null,"abstract":"Introduction. Bladder cancer (BC) is a significant public health problem due to its high likelihood of relapse and local or metastatic progression, which requires big government funding. The study of the urothelial precancerous lesions contributes to the earlier disease detection and influences the management strategy. However, experts argue on how to interpret pathological processes of the urothelium, therefore, the purpose of our study was to evaluate clinical and morphological features of inflammatory, precancerous, and cancerous lesions of the urothelium. Materials and methods. The study included 120 patients (77 men and 43 women) with inflammatory, pre-cancerous, and cancerous lesions of the urothelium. The patients were divided into 4 subgroups: subgroup I included 11 patients with reactive atypia of the urothelium; subgroup II involved 24 patients with urothelial dysplasia; subgroup III consisted of 51 patients with non–muscle-invasive BC (NMIBC); and subgroup IV included 34 patients with muscle-invasive BC (MIBC). We assessed clinically gender, age, size, lesion location, singleness and multiplicity of lesions, and the presence of blood in the urine. We also performed pathological assessment for subgroups III and IV: we studied the level of tumor invasion and the tumor grade. For statistical processing of the data, we used IBM SPSS Statistics (version 23) for Windows. Results. The study revealed tumor lesions to be more common in men than in women. The size of urothelial dysplasia in women was significantly greater than in men (U=26; p=0.019). In subgroup III (NMIBC), multiple lesions were more common with increasing age (U=155.5; p=0.048). In subgroup IV (MIBC), younger patients were found to have less differentiated tumors. Conclusion. This study demonstrated the clinical and morphological features of patients with inflammatory, precancerous, and cancerous lesions of the bladder. Keywords: bladder cancer, muscle non-invasive bladder cancer, muscle invasive bladder cancer, urothelial dysplasia, reactive atypia, oncology, pathology","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69279693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.31088/cem2022.11.2.63-70
T. Tral, G. Tolibova, I. Kogan
Introduction. Demographic decline is one of the main challenges to modern society. Thus, the problem of early pregnancy loss retains medical and social significance regardless of the way of conception. The endometrium continues to be an underestimated component in the reproduction process, while studies ofthe gravid endometrium are few. The aim of the paper was to evaluate expression of progesterone-induced blocking factor (PIBF) in the gravid endometrium in early pregnancy loss following IVF methods. Materials and methods. Histological and immunohistochemical studies were carried out on samples of products of conception (POCs). Seventy-seven POCs with normal chorionic villi karyotype were collected from women with missed miscarriage of 5–8 weeks of embryohistological term after IVF; the other 15 samples of elective POCs were collected at the same term. We evaluated PIBF expression in glands and stroma of the gravid endometrium compact layer using immunohistochemical method. Results. Morphological features of missed miscarriage after IVF were characterized by violated transformation and decidualization of the gravid endometrium. Immunohistochemistry showed decreased PIBF expression in the experimental groups regardless of endometrial transformation options. It might indicate disturbances in the gravid endometrium and implantation compared to the control group (p<0.001). Conclusion. A comprehensive morphological evaluation of POCs with PIBF expression assessment will allow to verify violation of transformational potential of glands and stroma of the gravid endometrium in cases of early pregnancy loss regardless of the way of conception. Keywords: missed abortion, infertility, IVF, progesterone-induced blocking factor, gravid transformation of the endometrium
{"title":"PIBF expression in the gravid endometrium in early pregnancy loss following assisted reproductive technologies","authors":"T. Tral, G. Tolibova, I. Kogan","doi":"10.31088/cem2022.11.2.63-70","DOIUrl":"https://doi.org/10.31088/cem2022.11.2.63-70","url":null,"abstract":"Introduction. Demographic decline is one of the main challenges to modern society. Thus, the problem of early pregnancy loss retains medical and social significance regardless of the way of conception. The endometrium continues to be an underestimated component in the reproduction process, while studies ofthe gravid endometrium are few. The aim of the paper was to evaluate expression of progesterone-induced blocking factor (PIBF) in the gravid endometrium in early pregnancy loss following IVF methods. Materials and methods. Histological and immunohistochemical studies were carried out on samples of products of conception (POCs). Seventy-seven POCs with normal chorionic villi karyotype were collected from women with missed miscarriage of 5–8 weeks of embryohistological term after IVF; the other 15 samples of elective POCs were collected at the same term. We evaluated PIBF expression in glands and stroma of the gravid endometrium compact layer using immunohistochemical method. Results. Morphological features of missed miscarriage after IVF were characterized by violated transformation and decidualization of the gravid endometrium. Immunohistochemistry showed decreased PIBF expression in the experimental groups regardless of endometrial transformation options. It might indicate disturbances in the gravid endometrium and implantation compared to the control group (p<0.001). Conclusion. A comprehensive morphological evaluation of POCs with PIBF expression assessment will allow to verify violation of transformational potential of glands and stroma of the gravid endometrium in cases of early pregnancy loss regardless of the way of conception. Keywords: missed abortion, infertility, IVF, progesterone-induced blocking factor, gravid transformation of the endometrium","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69280526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.31088/cem2022.11.3.45-55
E. Borkhunova, S. Pozyabin, S.V. Saroyan, A. Dovgii
Introduction. Regenerative medicine is a promising and actively developing scientific area. Of particular interest are studies related to the mechanisms of biological drug action, a particular focus being on secretomes. The term “secretomes” refers to numerous cytokines, growth factors, and other proteins and peptides that are secreted by cells and regulate biological processes. Most published literature on biologi-cal effects of individual cytokines and cell secretomes during reparative regeneration processes have been carried out in vitro. Studies describing morphological control, i.e. assessing structural changes in tissue and identifying the key processes influenced by cytokines during regeneration, are scarce, and further research is needed. This article presents the results of evaluating the reparative corneal regeneration with secretome produced by mesenchymal stem cells (MSCs). Materials and methods. We divided guinea pigs (N=30) into three groups (experimental, comparison, and control). Under isoflurane anesthesia, each animal received a mechanical corneal defect 5 mm in diameter affecting 2/3 of the cornea in depth. We observed the animals and performed daily ophthalmological examinations. Animals were sacrificed on days 1, 5, 11, and 28 after the manipulation with an overdose of anesthesia. Then, we performed histological and micromorphometric evaluation. Results. We revealed that under the influence of cytokines, corneal regeneration was with less pronounced inflammation and exudation. The restoration of corneal curvature was full whereas that of corneal transparency was partial. Microscopic examination of the samples obtained from the animals of the experimental group showed that they had a lower inflammatory cell response, earlier epithelialization, restored thickness of the regenerate, and less scar-like tissue formation in the cornea than those in the comparison and control groups. We observed the appearance of hypovascular and avascular foci in the structure of the regenerate connective tissue, which may be associated with the remodeling process. This factor may also be responsible for the observed partial restoration of corneal transparency. Conclusion. The secret of stem cells has a positive effect on the healing of corneal wounds. The inflammation is moderate. The corneal regenerate is of nubecula type; corneal transparency is partially restored. Keywords: mesenchymal stem cells, secretome, cytokines, cornea, wound, reparative regeneration
{"title":"Peculiarities of reparative corneal regeneration applying stem cell secretome","authors":"E. Borkhunova, S. Pozyabin, S.V. Saroyan, A. Dovgii","doi":"10.31088/cem2022.11.3.45-55","DOIUrl":"https://doi.org/10.31088/cem2022.11.3.45-55","url":null,"abstract":"Introduction. Regenerative medicine is a promising and actively developing scientific area. Of particular interest are studies related to the mechanisms of biological drug action, a particular focus being on secretomes. The term “secretomes” refers to numerous cytokines, growth factors, and other proteins and peptides that are secreted by cells and regulate biological processes. Most published literature on biologi-cal effects of individual cytokines and cell secretomes during reparative regeneration processes have been carried out in vitro. Studies describing morphological control, i.e. assessing structural changes in tissue and identifying the key processes influenced by cytokines during regeneration, are scarce, and further research is needed. This article presents the results of evaluating the reparative corneal regeneration with secretome produced by mesenchymal stem cells (MSCs). Materials and methods. We divided guinea pigs (N=30) into three groups (experimental, comparison, and control). Under isoflurane anesthesia, each animal received a mechanical corneal defect 5 mm in diameter affecting 2/3 of the cornea in depth. We observed the animals and performed daily ophthalmological examinations. Animals were sacrificed on days 1, 5, 11, and 28 after the manipulation with an overdose of anesthesia. Then, we performed histological and micromorphometric evaluation. Results. We revealed that under the influence of cytokines, corneal regeneration was with less pronounced inflammation and exudation. The restoration of corneal curvature was full whereas that of corneal transparency was partial. Microscopic examination of the samples obtained from the animals of the experimental group showed that they had a lower inflammatory cell response, earlier epithelialization, restored thickness of the regenerate, and less scar-like tissue formation in the cornea than those in the comparison and control groups. We observed the appearance of hypovascular and avascular foci in the structure of the regenerate connective tissue, which may be associated with the remodeling process. This factor may also be responsible for the observed partial restoration of corneal transparency. Conclusion. The secret of stem cells has a positive effect on the healing of corneal wounds. The inflammation is moderate. The corneal regenerate is of nubecula type; corneal transparency is partially restored. Keywords: mesenchymal stem cells, secretome, cytokines, cornea, wound, reparative regeneration","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69280897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.31088/cem2022.11.4.25-37
А.Yu. Shamanova, Е.L. Каzachkov, I. Panova
Introduction. Early diagnosis and prediction of distant metastases in choroidal melanoma patients based on morphological and IHC assessment of the components of the tumor microenvironment is a topical issue. The aim was to evaluate the IHC expression of MMP-9 and type IV collagen in metastatic choroidal melanoma. Materials and methods. We analyzed 43 cases of choroidal melanoma T2(a,b,c)-3N0M0-1 during 2013–2017. The patients were divided into two groups: group 1 included patients with primary choroidal melanoma without distant metastases (N=25) and group 2 included patients with primary choroidal melanoma with distant liver metastases (N=18). We performed an IHC assay of the surgical samples with MMP-9 (Poly) (MMP-9) and Collagen-IV (Clone CIV 22) (Col4) antibodies. Qualitative, semi-quantitative, and quantita-tive parameters were evaluated with digital pathology software. We developed a semi-quantitative method for estimating the intensity of IHC expression of these markers (in scores) in choroidal melanoma. Results. The study included 22 female and 21 male patients (51.2% and 48.8%, respectively), the average age being 60.5 years. The thickness of choroidal melanoma averaged 8.3 mm; the average diameter of the tumor was 12.3 mm. We detected strong MMP-9 expression in tumor cells and their microenvironment and remodeled collagen framework in tumors with pronounced tumor necrosis, thickness, and scleral involve-ment. A more pronounced expression of MMP-9 was associated with an increase in isolated type IV collagen fibers in the extracellular matrix (ECM) of the metastatic choroidal melanoma. Conclusion. During the growth and progression of choroidal melanoma, the components of the microenvi-ronment and tumor cells have a mutual effect with the disorganization of ECM components. Indicators of IHC expression (MMP-9, Col4) in a tumor should not be considered as a diagnostic marker of metastatic choroidal melanoma. However, they can be used in clinical practice when monitoring the course of the disease and in studying the mechanisms of remodeling of the tumor microenvironment. Keywords: choroidal melanoma, MMP-9, type IV collagen, metastasis
{"title":"Morphological features of the distribution of extracellular matrix components MMP-9 and type IV collagen in metastatic choroidal melanoma","authors":"А.Yu. Shamanova, Е.L. Каzachkov, I. Panova","doi":"10.31088/cem2022.11.4.25-37","DOIUrl":"https://doi.org/10.31088/cem2022.11.4.25-37","url":null,"abstract":"Introduction. Early diagnosis and prediction of distant metastases in choroidal melanoma patients based on morphological and IHC assessment of the components of the tumor microenvironment is a topical issue. The aim was to evaluate the IHC expression of MMP-9 and type IV collagen in metastatic choroidal melanoma. Materials and methods. We analyzed 43 cases of choroidal melanoma T2(a,b,c)-3N0M0-1 during 2013–2017. The patients were divided into two groups: group 1 included patients with primary choroidal melanoma without distant metastases (N=25) and group 2 included patients with primary choroidal melanoma with distant liver metastases (N=18). We performed an IHC assay of the surgical samples with MMP-9 (Poly) (MMP-9) and Collagen-IV (Clone CIV 22) (Col4) antibodies. Qualitative, semi-quantitative, and quantita-tive parameters were evaluated with digital pathology software. We developed a semi-quantitative method for estimating the intensity of IHC expression of these markers (in scores) in choroidal melanoma. Results. The study included 22 female and 21 male patients (51.2% and 48.8%, respectively), the average age being 60.5 years. The thickness of choroidal melanoma averaged 8.3 mm; the average diameter of the tumor was 12.3 mm. We detected strong MMP-9 expression in tumor cells and their microenvironment and remodeled collagen framework in tumors with pronounced tumor necrosis, thickness, and scleral involve-ment. A more pronounced expression of MMP-9 was associated with an increase in isolated type IV collagen fibers in the extracellular matrix (ECM) of the metastatic choroidal melanoma. Conclusion. During the growth and progression of choroidal melanoma, the components of the microenvi-ronment and tumor cells have a mutual effect with the disorganization of ECM components. Indicators of IHC expression (MMP-9, Col4) in a tumor should not be considered as a diagnostic marker of metastatic choroidal melanoma. However, they can be used in clinical practice when monitoring the course of the disease and in studying the mechanisms of remodeling of the tumor microenvironment. Keywords: choroidal melanoma, MMP-9, type IV collagen, metastasis","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69281148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}