Pub Date : 2021-01-01DOI: 10.31088/cem2021.10.3.14-20
D. S. Shvorob, T. I. Shevchenko, R.B. Kondratyk
Colorectal cancer ranks third in the morbidity structure among all malignant tumors and includes sporadic and hereditary neoplasms. Cancer genome sequencing has revealed numerous mutation variants that determine the ways colorectal carcinoma progresses. The course, prognosis, and management strategy of the disease vary greatly depending on the subtype of a molecular tumor. This literature review discusses the latest data on the variants of colorectal cancer oncogenesis and presents the phenotypic model classification based on them. Immunohistochemistry (IHC) is suggested for determining the individual tumor characteristics. The article also clarifies the Bethesda panel used to detect microsatellite instability, markers for Lynch syndrome, and a list of IHC markers for determining the phenotypic model of colorectal carcinoma. Keywords: colorectal cancer, phenotypic models, consensus molecular subtypes (CMS), immunohisto-chemistry, Bethesda panel, Lynch syndrome
{"title":"Diagnosis of molecular subtypes of colorectal cancer using immunohistochemistry","authors":"D. S. Shvorob, T. I. Shevchenko, R.B. Kondratyk","doi":"10.31088/cem2021.10.3.14-20","DOIUrl":"https://doi.org/10.31088/cem2021.10.3.14-20","url":null,"abstract":"Colorectal cancer ranks third in the morbidity structure among all malignant tumors and includes sporadic and hereditary neoplasms. Cancer genome sequencing has revealed numerous mutation variants that determine the ways colorectal carcinoma progresses. The course, prognosis, and management strategy of the disease vary greatly depending on the subtype of a molecular tumor. This literature review discusses the latest data on the variants of colorectal cancer oncogenesis and presents the phenotypic model classification based on them. Immunohistochemistry (IHC) is suggested for determining the individual tumor characteristics. The article also clarifies the Bethesda panel used to detect microsatellite instability, markers for Lynch syndrome, and a list of IHC markers for determining the phenotypic model of colorectal carcinoma. Keywords: colorectal cancer, phenotypic models, consensus molecular subtypes (CMS), immunohisto-chemistry, Bethesda panel, Lynch syndrome","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69279311","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 : 2021-01-01DOI: 10.31088/cem2021.10.3.5-13
E. V. Kusraeva
Hypersensitivity pneumonitis (HP) is an immune-mediated disease that manifests in susceptible individu-als after exposure to a provoking inhalation factor. The literature review describes etiological factors of the disease, its epidemiology and pathogenesis, as well as clinical features of various disease courses. A new clinical and morphological classification of HP is also presented. We analyzed changes in functional tests (external respiration function), CT images, cellular components of bronchoalveolar lavages, and modern approaches to the disease treatment. The review includes detailed morphological criteria according to the new classification, which will facilitate the diagnosis by pathologists. Since the diagnosis of the condition presents significant challenges, there are histological criteria for differential diagnosis of the fibrotic HP and usual interstitial pneumonia (idiopathic pulmonary fibrosis), sarcoidosis, lymphoid interstitial pneumonia, and pulmonary manifestations of connective tissue diseases. Keywords: hypersensitivity pneumonitis, interstitial lung diseases
{"title":"Clinical and morphological characteristics of hypersensitivity pneumonitis","authors":"E. V. Kusraeva","doi":"10.31088/cem2021.10.3.5-13","DOIUrl":"https://doi.org/10.31088/cem2021.10.3.5-13","url":null,"abstract":"Hypersensitivity pneumonitis (HP) is an immune-mediated disease that manifests in susceptible individu-als after exposure to a provoking inhalation factor. The literature review describes etiological factors of the disease, its epidemiology and pathogenesis, as well as clinical features of various disease courses. A new clinical and morphological classification of HP is also presented. We analyzed changes in functional tests (external respiration function), CT images, cellular components of bronchoalveolar lavages, and modern approaches to the disease treatment. The review includes detailed morphological criteria according to the new classification, which will facilitate the diagnosis by pathologists. Since the diagnosis of the condition presents significant challenges, there are histological criteria for differential diagnosis of the fibrotic HP and usual interstitial pneumonia (idiopathic pulmonary fibrosis), sarcoidosis, lymphoid interstitial pneumonia, and pulmonary manifestations of connective tissue diseases. Keywords: hypersensitivity pneumonitis, interstitial lung diseases","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69279472","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 : 2021-01-01DOI: 10.31088/CEM2021.10.1.5-10
N. Yaglova, S. Obernikhin, V. Yaglov, S. Nazimova
Skin represents a natural barrier and a site of contact with antigens. Skin demonstrates higher intensity of immune reactions compared to other organs, which implies the additional cell interactions. Dendritic cells are traditionally considered as the main antigenpresenting cells of the skin, however, in recent years, some data on the ability of another population, mast cells, to perform antigenpresenting functions have appeared. The review presents novel data on the interaction of skin dendritic and mast cells, including formation of immune synapses, exchange of surface molecules, and transfer of secretory material. The authors have developed and presented a new concept for the initiation and modulation of immune responses provided by the functional dendritic cell–mast cell complex. Keywords: dendritic cells, mast cells, skin, immunological synapse, degranulatory synapse, immune response
{"title":"Role of skin dendritic and mast cells communications in triggering immune\u0000 reactions","authors":"N. Yaglova, S. Obernikhin, V. Yaglov, S. Nazimova","doi":"10.31088/CEM2021.10.1.5-10","DOIUrl":"https://doi.org/10.31088/CEM2021.10.1.5-10","url":null,"abstract":"Skin represents a natural barrier and a site of contact with antigens. Skin demonstrates higher intensity of immune reactions compared to other organs, which implies the additional cell interactions. Dendritic cells are traditionally considered as the main antigenpresenting cells of the skin, however, in recent years, some data on the ability of another population, mast cells, to perform antigenpresenting functions have appeared. The review presents novel data on the interaction of skin dendritic and mast cells, including formation of immune synapses, exchange of surface molecules, and transfer of secretory material. The authors have developed and presented a new concept for the initiation and modulation of immune responses provided by the functional dendritic cell–mast cell complex. Keywords: dendritic cells, mast cells, skin, immunological synapse, degranulatory synapse, immune response","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69279685","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 : 2021-01-01DOI: 10.31088/cem2021.10.s4.34-41
K. Midiber, A. E. Biryukov, V. Pechnikova, N. A. Gracheva, N. Shakhpazyan, Z. Gioeva, L. Mikhaleva
Introduction. Despite various diagnostic testing and treatment options, stomach cancer ranks 5th in terms of global morbidity among all cancers. Diffuse gastric cancer occurs more frequently in younger patients and has a more aggressive course than the intestinal type. Modern ideas about the etiology, pathogenesis, and molecular structure of a tumor allow us to take a new look at diffuse gastric cancer in the light of revised classifications, recommendations, as well as approaches to the interpretation of morphological research data. Therefore, the study aimed to conduct a multifactorial analysis of patients with diffuse gastric cancer. Materials and methods. The study included 124 patients with diffuse gastric cancer. Clinical data (medical histories, protocols of endoscopic and surgical operations, sex, and age groups) and the primary tumor localization were analyzed. We formed a group of 25 observations out of 124 patients. In the group, we carried out a range of diagnostic measures: histological, histochemical, immunohistochemical, and molecular assays, as well as PCR testing. Results. In the group of 124 patients, the age of men averaged 67.5 (±12.4) years and that of women, 71 (±15.41) years. The malignant tumors were more frequently detected in distal parts of the stomach. In the group of 25 patients, Helicobacter pylori were present only in 2 cases. We detected the Epstein-Barr virus in 11 patients out of 25 using real-time PCR method. A study of the immunophenotype of diffuse gastric cancer using a wide panel of antibodies demonstrated heterogeneity of expression in both components of a malignant tumor. The expression of CK7, Muc1, Muc2, and Muc5AC markers in patients with a microsatellite unstable molecular subtype was noteworthy. Conclusion. The immunophenotypic heterogeneity of diffuse gastric cancer requires further research. It is necessary to create a standardized pathology evaluation protocol, including molecular and immunohistochemical tests that is the basis for modern management of cancer patients with diffuse gastric cancer. Keywords: gastric cancer, surgical pathology, immunohistochemistry, molecular genetics
{"title":"Clinical and morphological heterogeneity of diffuse gastric cancer","authors":"K. Midiber, A. E. Biryukov, V. Pechnikova, N. A. Gracheva, N. Shakhpazyan, Z. Gioeva, L. Mikhaleva","doi":"10.31088/cem2021.10.s4.34-41","DOIUrl":"https://doi.org/10.31088/cem2021.10.s4.34-41","url":null,"abstract":"Introduction. Despite various diagnostic testing and treatment options, stomach cancer ranks 5th in terms of global morbidity among all cancers. Diffuse gastric cancer occurs more frequently in younger patients and has a more aggressive course than the intestinal type. Modern ideas about the etiology, pathogenesis, and molecular structure of a tumor allow us to take a new look at diffuse gastric cancer in the light of revised classifications, recommendations, as well as approaches to the interpretation of morphological research data. Therefore, the study aimed to conduct a multifactorial analysis of patients with diffuse gastric cancer. Materials and methods. The study included 124 patients with diffuse gastric cancer. Clinical data (medical histories, protocols of endoscopic and surgical operations, sex, and age groups) and the primary tumor localization were analyzed. We formed a group of 25 observations out of 124 patients. In the group, we carried out a range of diagnostic measures: histological, histochemical, immunohistochemical, and molecular assays, as well as PCR testing. Results. In the group of 124 patients, the age of men averaged 67.5 (±12.4) years and that of women, 71 (±15.41) years. The malignant tumors were more frequently detected in distal parts of the stomach. In the group of 25 patients, Helicobacter pylori were present only in 2 cases. We detected the Epstein-Barr virus in 11 patients out of 25 using real-time PCR method. A study of the immunophenotype of diffuse gastric cancer using a wide panel of antibodies demonstrated heterogeneity of expression in both components of a malignant tumor. The expression of CK7, Muc1, Muc2, and Muc5AC markers in patients with a microsatellite unstable molecular subtype was noteworthy. Conclusion. The immunophenotypic heterogeneity of diffuse gastric cancer requires further research. It is necessary to create a standardized pathology evaluation protocol, including molecular and immunohistochemical tests that is the basis for modern management of cancer patients with diffuse gastric cancer. Keywords: gastric cancer, surgical pathology, immunohistochemistry, molecular genetics","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69279984","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 : 2021-01-01DOI: 10.31088/cem2021.10.s4.61-67
O. Kovaleva, I. Boulytcheva, A. N. Gratchev, N. S. Babkin, E. R. Musaev, N. Kushlinskii
Introduction. Chordomas are rare malignant neoplasms that are highly recurrent and with limited treatment options. Invasion of the vital structures of the nervous system complicates their treatment. The search for new methods of drug therapy for chordomas is an urgent problem. The aim of the research was to study PD-L1 expression in tumor cells and tumor infiltrating lymphocytes (TILs) in chordoma samples and its interrelation with tumor characteristics and prognosis. Materials and methods. We analyzed PD-L1 expression in 30 primary chordomas using immunohistochemistry and differences in independent groups using Chi-square and Kruskal–Wallis tests. Survival analysis was performed by constructing Kaplan–Meier survival curves. We compared the significance of differences with the logarithmic rank test. Differences were considered significant at p<0.05. Results. PD-L1 expression was detected in tumor cells in 43% of samples and in TILs in 80%. PD-L1 expres-sion in tumor cells and TILs was not associated with the clinical features of the disease. However, PD-L1 expression in tumor cells in all samples correlates positively with the content of this marker in TILs (r=0.409, p=0.028). Different histological variants of chordomas were shown to differ in the content of PD-L1 in both tumor cells and TILs. PD-L1 expression in tumor cells is not a predictor of the disease, while its expression in TILs tends to be a marker of a favorable prognosis (HR=0.1429; p=0.0570). Conclusion. We found the lowest level of PD-L1 expression in both tumor cells and TILs in dedifferentiated chordoma. PD-L1 expression in TILs is associated with a favorable prognosis of chordomas and indicates the potential for the use of checkpoint inhibitors in therapy. Keywords: chordoma, PD-L1, lymphocytes, prognosis, survival
{"title":"Prognostic significance of programmed cell death receptor ligand PD-L1 expression in chordoma","authors":"O. Kovaleva, I. Boulytcheva, A. N. Gratchev, N. S. Babkin, E. R. Musaev, N. Kushlinskii","doi":"10.31088/cem2021.10.s4.61-67","DOIUrl":"https://doi.org/10.31088/cem2021.10.s4.61-67","url":null,"abstract":"Introduction. Chordomas are rare malignant neoplasms that are highly recurrent and with limited treatment options. Invasion of the vital structures of the nervous system complicates their treatment. The search for new methods of drug therapy for chordomas is an urgent problem. The aim of the research was to study PD-L1 expression in tumor cells and tumor infiltrating lymphocytes (TILs) in chordoma samples and its interrelation with tumor characteristics and prognosis. Materials and methods. We analyzed PD-L1 expression in 30 primary chordomas using immunohistochemistry and differences in independent groups using Chi-square and Kruskal–Wallis tests. Survival analysis was performed by constructing Kaplan–Meier survival curves. We compared the significance of differences with the logarithmic rank test. Differences were considered significant at p<0.05. Results. PD-L1 expression was detected in tumor cells in 43% of samples and in TILs in 80%. PD-L1 expres-sion in tumor cells and TILs was not associated with the clinical features of the disease. However, PD-L1 expression in tumor cells in all samples correlates positively with the content of this marker in TILs (r=0.409, p=0.028). Different histological variants of chordomas were shown to differ in the content of PD-L1 in both tumor cells and TILs. PD-L1 expression in tumor cells is not a predictor of the disease, while its expression in TILs tends to be a marker of a favorable prognosis (HR=0.1429; p=0.0570). Conclusion. We found the lowest level of PD-L1 expression in both tumor cells and TILs in dedifferentiated chordoma. PD-L1 expression in TILs is associated with a favorable prognosis of chordomas and indicates the potential for the use of checkpoint inhibitors in therapy. Keywords: chordoma, PD-L1, lymphocytes, prognosis, survival","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69280050","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 : 2021-01-01DOI: 10.31088/cem2021.10.s4.7-22
L. Gurevich, E. Bondarenko, O. Vasyukova, L. Mikhaleva
The paper reviews the role of transcription factors that are part of the Yamanaka cocktail (OCT4, SOX2, KLF4, and c-Myc) in the mechanisms of tumor stem cell (TSC) differentiation (a pool of pluripotent cells), their participation in the malignant transformation of somatic cells, and in tumor progression. Their increased proliferative activity, which determines their malignant potential, was believed to be the main feature of tumor cells. Currently, there is more evidence supporting another concept that explains the continued tumor growth, metastasis, and resistance to therapy of most malignant tumors with a small, rest-ing, and rarely dividing population of pluripotent tumor cells. Year 2006 is considered to be the beginning of a new direction in developmental biology when Japanese researchers K. Takahashi and S. Yamanaka published the results of their studies on the properties of embryonic stem cells and experiments on direct reprogramming of somatic terminally differentiated cells.The research proved that four transcription factors were sufficient to maintain the pluripotent properties of cells, namely Oct4, SOX2, KLF4, and c-Myc, which were later called the Yamanaka cocktail. Such factors as SOX2and Oct4 are at the top of the hierarchy of transcription factors that regulate the pluripotent proper-ties of cells, their differentiation, and dedifferentiation. TSCs represent, albeit a complex, but very promising target for the development of innovative products for the diagnosis of and targeted therapy for neoplasms. From this point of view, the factors of pluripotency, which are parts of the Yamanaka cocktail, could be such promising targets, whose effect will probably be able to suppress or reduce the malignant potential of the most aggressive tumors and even prevent carcinogenic transformation in cases of precancerous pathology. Keywords: Yamanaka cocktail, OCT4, SOX2, KLF4, c-Myc, malignant transformation
{"title":"The role of Yamanaka cocktail transcription factors (OCT4, SOX2, KLF4, c-Myc) in the differentiation of somatic cells, their malignant transformation, and tumor progression","authors":"L. Gurevich, E. Bondarenko, O. Vasyukova, L. Mikhaleva","doi":"10.31088/cem2021.10.s4.7-22","DOIUrl":"https://doi.org/10.31088/cem2021.10.s4.7-22","url":null,"abstract":"The paper reviews the role of transcription factors that are part of the Yamanaka cocktail (OCT4, SOX2, KLF4, and c-Myc) in the mechanisms of tumor stem cell (TSC) differentiation (a pool of pluripotent cells), their participation in the malignant transformation of somatic cells, and in tumor progression. Their increased proliferative activity, which determines their malignant potential, was believed to be the main feature of tumor cells. Currently, there is more evidence supporting another concept that explains the continued tumor growth, metastasis, and resistance to therapy of most malignant tumors with a small, rest-ing, and rarely dividing population of pluripotent tumor cells. Year 2006 is considered to be the beginning of a new direction in developmental biology when Japanese researchers K. Takahashi and S. Yamanaka published the results of their studies on the properties of embryonic stem cells and experiments on direct reprogramming of somatic terminally differentiated cells.The research proved that four transcription factors were sufficient to maintain the pluripotent properties of cells, namely Oct4, SOX2, KLF4, and c-Myc, which were later called the Yamanaka cocktail. Such factors as SOX2and Oct4 are at the top of the hierarchy of transcription factors that regulate the pluripotent proper-ties of cells, their differentiation, and dedifferentiation. TSCs represent, albeit a complex, but very promising target for the development of innovative products for the diagnosis of and targeted therapy for neoplasms. From this point of view, the factors of pluripotency, which are parts of the Yamanaka cocktail, could be such promising targets, whose effect will probably be able to suppress or reduce the malignant potential of the most aggressive tumors and even prevent carcinogenic transformation in cases of precancerous pathology. Keywords: Yamanaka cocktail, OCT4, SOX2, KLF4, c-Myc, malignant transformation","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69280075","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 : 2021-01-01DOI: 10.31088/cem2021.10.2.13-20
I. Vasilenko, R.B. Kondratyk, I. S. Grekov, A. M. Yarkov
Introduction. The rapid development of basic science enabled us to significantly expand our understanding of various intercellular interactions. Epithelial-mesenchymal transition (EMT) is known to play a key role in certain tissue formation in the embryonic period. However, recent data show that EMT can also be observed in some pathological conditions, in particular, in various neoplasm development. This suggests that there are a number of alternative and fundamentally new mechanisms for the tumor formation and progression. Thus, EMT, which occurs in carcinomas, increases the invasiveness, immunoresistance, immunity to therapy, and the metastatic potential. Knowledge of EMT features and their timely recognition in morphological tumor diagnosis is of great predictive importance for patients. The aim of the research was to study the morphologi-cal features of epithelial-mesenchymal transition in the main types of gastric cancer. Materials and methods. We studied specimens of gastric carcinomas (N=64) including 31 cases of diffuse type, 19 cases of intestinal type, and 14 cases of mixed type. Results. All cases of the diffuse carcinoma group showed spread EMT features, which appeared already in the mucosa and completed with positive vimentin expression in 93.5% of cases. The malignant cell prolifera-tive activity was low; however, in 29% of cases we detected areas of moderate or even high activity. In the intestinal type gastric cancer, EMT developed as a result of tumor progression, it arose more often in the deeper layers and was incomplete and focal. As a rule, the proliferative activity of tumor cells was high and moderate. Vascular invasion occurred more often in diffuse type (90.3%), less often in mixed type (71.4%), and even less often in the intestine type (55.8%) gastric carcinoma. Conclusion. The variety of morphological features of EMT, its frequency, prevalence, completeness, and sequence in the development of various types of gastric cancer determines the features of their clinical manifestation and influences their further management. Keywords: gastric cancer, diagnosis, histological main types, EMT, morphopathology
{"title":"Epithelial-mesenchymal transition in main types of gastric carcinoma","authors":"I. Vasilenko, R.B. Kondratyk, I. S. Grekov, A. M. Yarkov","doi":"10.31088/cem2021.10.2.13-20","DOIUrl":"https://doi.org/10.31088/cem2021.10.2.13-20","url":null,"abstract":"Introduction. The rapid development of basic science enabled us to significantly expand our understanding of various intercellular interactions. Epithelial-mesenchymal transition (EMT) is known to play a key role in certain tissue formation in the embryonic period. However, recent data show that EMT can also be observed in some pathological conditions, in particular, in various neoplasm development. This suggests that there are a number of alternative and fundamentally new mechanisms for the tumor formation and progression. Thus, EMT, which occurs in carcinomas, increases the invasiveness, immunoresistance, immunity to therapy, and the metastatic potential. Knowledge of EMT features and their timely recognition in morphological tumor diagnosis is of great predictive importance for patients. The aim of the research was to study the morphologi-cal features of epithelial-mesenchymal transition in the main types of gastric cancer. Materials and methods. We studied specimens of gastric carcinomas (N=64) including 31 cases of diffuse type, 19 cases of intestinal type, and 14 cases of mixed type. Results. All cases of the diffuse carcinoma group showed spread EMT features, which appeared already in the mucosa and completed with positive vimentin expression in 93.5% of cases. The malignant cell prolifera-tive activity was low; however, in 29% of cases we detected areas of moderate or even high activity. In the intestinal type gastric cancer, EMT developed as a result of tumor progression, it arose more often in the deeper layers and was incomplete and focal. As a rule, the proliferative activity of tumor cells was high and moderate. Vascular invasion occurred more often in diffuse type (90.3%), less often in mixed type (71.4%), and even less often in the intestine type (55.8%) gastric carcinoma. Conclusion. The variety of morphological features of EMT, its frequency, prevalence, completeness, and sequence in the development of various types of gastric cancer determines the features of their clinical manifestation and influences their further management. Keywords: gastric cancer, diagnosis, histological main types, EMT, morphopathology","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69279692","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 : 2021-01-01DOI: 10.31088/cem2021.10.2.50-56
E. Mishina, M. Zatolokina, M. Mnikhovich
Introduction. Skin expansion is known to be the most effective way to obtain skin for alloplastic closing of large defects, and it has proven to be successfully used in various fields of surgery, cosmetology, and traumatology. At the same time, the issues of skin flap restructuring when it is stretched and possible range of its application are still relevant. In this regard, the aim was to study the adaptive skin rearrangements of the fibrous skeleton in a murine skin expansion model. Materials and methods. We used the skin of mature male Wistar rats (N=30) after a 2-week stretching. We utilized a complex morphological light and electron microscopy approach as well as an immunohistochemi-cal method to determine the types of collagen and to study the alterations in skin samples. Results. We revealed pronounced reactive changes in the skin structural components in the skin expansion area. On day 14, we observed a decrease in the epidermal cell layer thickness as well as stretching, partial disorganization, and damage of dermal fibrous structure. At the same time, cellular mechanisms of regen-eration and activation of collagen synthesis were launched, the morphological substrate of which was (1) a significant 2.7-fold increase in the number density of fibroblasts, which produce substances for building fibrous structures, (2) a five-fold increase in macrophages, which are a catalyst for the fibroblast functional activity and (3) a collagen fiber types’ redistribution s with Type III collagen structures’ predominance. Conclusion. The results indicate, first of all, the restructuring of the dermal fibrous component, which im-plies reparative and restorative processes. These must be taken into account in clinical practice to achieve not only an esthetic effect but also the subsequent adequate functioning and vital activity of the skin flap. Keywords: skin expansion, fibrous dermis, remodeling, skin, hyperextension
{"title":"Structural dermis remodeling in a skin expansion rat model","authors":"E. Mishina, M. Zatolokina, M. Mnikhovich","doi":"10.31088/cem2021.10.2.50-56","DOIUrl":"https://doi.org/10.31088/cem2021.10.2.50-56","url":null,"abstract":"Introduction. Skin expansion is known to be the most effective way to obtain skin for alloplastic closing of large defects, and it has proven to be successfully used in various fields of surgery, cosmetology, and traumatology. At the same time, the issues of skin flap restructuring when it is stretched and possible range of its application are still relevant. In this regard, the aim was to study the adaptive skin rearrangements of the fibrous skeleton in a murine skin expansion model. Materials and methods. We used the skin of mature male Wistar rats (N=30) after a 2-week stretching. We utilized a complex morphological light and electron microscopy approach as well as an immunohistochemi-cal method to determine the types of collagen and to study the alterations in skin samples. Results. We revealed pronounced reactive changes in the skin structural components in the skin expansion area. On day 14, we observed a decrease in the epidermal cell layer thickness as well as stretching, partial disorganization, and damage of dermal fibrous structure. At the same time, cellular mechanisms of regen-eration and activation of collagen synthesis were launched, the morphological substrate of which was (1) a significant 2.7-fold increase in the number density of fibroblasts, which produce substances for building fibrous structures, (2) a five-fold increase in macrophages, which are a catalyst for the fibroblast functional activity and (3) a collagen fiber types’ redistribution s with Type III collagen structures’ predominance. Conclusion. The results indicate, first of all, the restructuring of the dermal fibrous component, which im-plies reparative and restorative processes. These must be taken into account in clinical practice to achieve not only an esthetic effect but also the subsequent adequate functioning and vital activity of the skin flap. Keywords: skin expansion, fibrous dermis, remodeling, skin, hyperextension","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69279218","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 : 2021-01-01DOI: 10.31088/cem2021.10.3.21-28
Kh M Akhrieva, E. A. Kogan, A.S. Tertychniy, O. Zayratyants, L. S. Selivanova
Introduction. Morphological diagnosis of inflammatory bowel diseases (IBDs) based on endoscopic biopsies remains a rather challenging task and does not always allow the pathologist to make the final conclusion. Difficulties arise due to the absence of a classical morphological picture in biopsy specimens as well as the lack of clinical and laboratory data. These issues may lead to an incorrect interpretation of the detected pathological changes and an erroneous conclusion. The aim of the study was to assess the quality of biopsy diagnosis of IBDs using Internet diagnostic tools, namely, the digitalized histological slides. Materials and methods. We created an Internet platform, which contained 100 scanned images of histologi-cal slides from 70 patients with suspected IBD. Based on our own practical experience and guidelines of international European and British societies of pathology, we arranged a survey. The diagnosis was made on the combined clinical and morphological approach, considering also a complex of clinical, laboratory, endoscopic, and morphological data. The first stage of the survey was anonymous and included a list of 25 questions. Ten pathologists, who agreed to take part in the study, completed the questionnaire. After statistical processing, the results were assessed using a Fleiss' kappa criterion. Results. The comparative analysis of morphological study showed that the participants were able to diagnose accurately only 71% of ulcerative colitis cases and 63% of Crohn’s disease cases. At the same time, the agreement coefficient demonstrated satisfactory values: the Fleiss' kappa was 0.34 and 0.25, respectively. In some cases, the participants found it difficult to perform a differential diagnosis between IBD and other forms of colitis and were not always capable of distinguishing ulcerative colitis from Crohn’s disease. A few of the individual criteria, on which the diagnosis is based, rarely reached agreement above a kappa of 0.5. The participants’ agreement was considered more often as “weak” and “satisfactory”. This is largely due to the fact that we did not discuss the exact criteria for the proposed parameters and that these parameters were divided into four degrees of severity from 0 to 3. Conclusion. The results showed the current discrepancies in the assessment of biopsies in patients with suspected IBD. The developed Internet platform provides additional significant opportunities to improve the quality of morphological diagnosis in ileal and colon biopsies by means of refining the criteria and their assessment in the final diagnosis statement. Keywords: inflammatory bowel disease, colitis, digital pathology
{"title":"Quality assessment of the inflammatory bowel disease biopsy diagnosis using digital images","authors":"Kh M Akhrieva, E. A. Kogan, A.S. Tertychniy, O. Zayratyants, L. S. Selivanova","doi":"10.31088/cem2021.10.3.21-28","DOIUrl":"https://doi.org/10.31088/cem2021.10.3.21-28","url":null,"abstract":"Introduction. Morphological diagnosis of inflammatory bowel diseases (IBDs) based on endoscopic biopsies remains a rather challenging task and does not always allow the pathologist to make the final conclusion. Difficulties arise due to the absence of a classical morphological picture in biopsy specimens as well as the lack of clinical and laboratory data. These issues may lead to an incorrect interpretation of the detected pathological changes and an erroneous conclusion. The aim of the study was to assess the quality of biopsy diagnosis of IBDs using Internet diagnostic tools, namely, the digitalized histological slides. Materials and methods. We created an Internet platform, which contained 100 scanned images of histologi-cal slides from 70 patients with suspected IBD. Based on our own practical experience and guidelines of international European and British societies of pathology, we arranged a survey. The diagnosis was made on the combined clinical and morphological approach, considering also a complex of clinical, laboratory, endoscopic, and morphological data. The first stage of the survey was anonymous and included a list of 25 questions. Ten pathologists, who agreed to take part in the study, completed the questionnaire. After statistical processing, the results were assessed using a Fleiss' kappa criterion. Results. The comparative analysis of morphological study showed that the participants were able to diagnose accurately only 71% of ulcerative colitis cases and 63% of Crohn’s disease cases. At the same time, the agreement coefficient demonstrated satisfactory values: the Fleiss' kappa was 0.34 and 0.25, respectively. In some cases, the participants found it difficult to perform a differential diagnosis between IBD and other forms of colitis and were not always capable of distinguishing ulcerative colitis from Crohn’s disease. A few of the individual criteria, on which the diagnosis is based, rarely reached agreement above a kappa of 0.5. The participants’ agreement was considered more often as “weak” and “satisfactory”. This is largely due to the fact that we did not discuss the exact criteria for the proposed parameters and that these parameters were divided into four degrees of severity from 0 to 3. Conclusion. The results showed the current discrepancies in the assessment of biopsies in patients with suspected IBD. The developed Internet platform provides additional significant opportunities to improve the quality of morphological diagnosis in ileal and colon biopsies by means of refining the criteria and their assessment in the final diagnosis statement. Keywords: inflammatory bowel disease, colitis, digital pathology","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69279322","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 : 2021-01-01DOI: 10.31088/cem2021.10.4.53-62
H. Gasparyan, S. Buloyan, A. Pogosyan, L.M. Arshakyan, L. Harutyunyan, R. Paronikyan, I. M. Nazaryan, S. Dashyan, E. Paronikyan
Introduction. Seizures provoke several morphological alterations in the brain structures. These alterations are primarily located in the hippocampal CA1 region and the entorhinal cortex. Recurrent seizures are common in patients with epilepsy. Therapeutic options for this disease are very limited and most of them are aimed at relieving symptoms. In most cases, to treat epilepsy, anti-seizure drugs are used. Nevertheless, one-third of affected individuals have resistance to them. Thus, the study of new effective agents that can prevent epileptogenesis is still an ongoing challenge. In this work, we aimed to study the neuroprotective activity of several new derivatives of tricyclic pyrazolyl substituted thieno[2,3-c]isoquinolins (SHD-89 and SHD-91) and pyrano[4,3-d]thieno[2,3-b]pyridines (SHD-78 and SHD-85) as potential anti-seizure drugs. Materials and methods. The study was performed on mice (n=60). The action of compounds SHD-78, SHD-85, SHD-89, and SHD-91 was tested in seizures with and without Corazol administration. Histopathological examinations were performed in the hippocampus and the entorhinal cortex in different experimental groups. Results. The study showed that under the action of SHD-89 and SHD-78, there was a reduction in the number of neurons and activation of glial cells in examined regions of the brain. SHD-91 caused severe neurode-generative effects with changes in the brain structure. In contrast, under the action of SHD-85, the number of neurons was higher and with lower activation of glial cells. Conclusion. Studies showed that among the tested compounds SHD-85 possessed moderate neuroprotective activity and reduced gliosis and neuronal loss induced by Corazol. Keywords: anti-seizure drugs, pyrazolylthienopyridines, hippocampus, entorhinal cortex, histopathological examination
{"title":"Pathological investigation of neuroprotective activity of new derivatives of fused pyrazolyl-thienopyridines in Corazol-induced seizures","authors":"H. Gasparyan, S. Buloyan, A. Pogosyan, L.M. Arshakyan, L. Harutyunyan, R. Paronikyan, I. M. Nazaryan, S. Dashyan, E. Paronikyan","doi":"10.31088/cem2021.10.4.53-62","DOIUrl":"https://doi.org/10.31088/cem2021.10.4.53-62","url":null,"abstract":"Introduction. Seizures provoke several morphological alterations in the brain structures. These alterations are primarily located in the hippocampal CA1 region and the entorhinal cortex. Recurrent seizures are common in patients with epilepsy. Therapeutic options for this disease are very limited and most of them are aimed at relieving symptoms. In most cases, to treat epilepsy, anti-seizure drugs are used. Nevertheless, one-third of affected individuals have resistance to them. Thus, the study of new effective agents that can prevent epileptogenesis is still an ongoing challenge. In this work, we aimed to study the neuroprotective activity of several new derivatives of tricyclic pyrazolyl substituted thieno[2,3-c]isoquinolins (SHD-89 and SHD-91) and pyrano[4,3-d]thieno[2,3-b]pyridines (SHD-78 and SHD-85) as potential anti-seizure drugs. Materials and methods. The study was performed on mice (n=60). The action of compounds SHD-78, SHD-85, SHD-89, and SHD-91 was tested in seizures with and without Corazol administration. Histopathological examinations were performed in the hippocampus and the entorhinal cortex in different experimental groups. Results. The study showed that under the action of SHD-89 and SHD-78, there was a reduction in the number of neurons and activation of glial cells in examined regions of the brain. SHD-91 caused severe neurode-generative effects with changes in the brain structure. In contrast, under the action of SHD-85, the number of neurons was higher and with lower activation of glial cells. Conclusion. Studies showed that among the tested compounds SHD-85 possessed moderate neuroprotective activity and reduced gliosis and neuronal loss induced by Corazol. Keywords: anti-seizure drugs, pyrazolylthienopyridines, hippocampus, entorhinal cortex, histopathological examination","PeriodicalId":36062,"journal":{"name":"Clinical and Experimental Morphology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69279637","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}
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