Lung Expression of Macrophage Markers CD68 and CD163, Angiotensin Converting Enzyme 2 (ACE2), and Caspase-3 in COVID-19.

Background and Objectives: The coronavirus (SARS-CoV-2) damages all systems and organs. Yet, to a greater extent, the lungs are particularly involved, due to the formation of diffuse exudative inflammation in the form of acute respiratory distress syndrome (ARDS) with next progression to pulmonary fibrosis. SARS-associated lung damage is accompanied by the pronounced activation of mononuclear cells, damage of the alveoli and microvessels, and the development of organized pneumonia. To study the expression of macrophage markers (CD68 and CD163), angiotensin-converting enzyme-2 (ACE2), and caspase-3 on the results of two fatal clinical observations of COVID-19. Materials and Methods: In both clinical cases, the female patients died from complications of confirmed COVID-19. Conventional morphological and immunohistochemical methods were used. Results: There was an acute exudative hemorrhagic pneumonia with the formation of hyaline membranes, focal organization of fibrin, stromal sclerosis, stasis, and thrombus formation in the lung vessels. Signs such as the formation of hyaline membranes, organization, and fibrosis were more pronounced in severe disease activity. The activation of CD68+/CD163+ macrophages could cause cell damage at an early stage of pneumonia development, and subsequently cause fibrotic changes in lung tissue. ACE2 expression in lung tissue was not detected in severe pneumonia, while in moderate pneumonia, weak expression was noted in individual cells of the alveolar epithelium and vascular endothelium. Conclusions: This finding could show the dependence of ACE2 expression on the severity of the inflammatory process in the lungs. The expression of caspase-3 was more pronounced in severe pneumonia.

MORPHOLOGICAL FEATURES OF MAXILLARY SINUS CYSTS BASED ON THE STUDY OF PARTICULAR HISTOCHEMICAL AND IMMUNOHISTOCHEMICAL FACTORS OF INFLAMMATION.

OBJECTIVE: The aim: To study the morphological structure and immunohistochemical markers of inflammatory cells in the maxillary sinus cyst wall. PATIENTS AND METHODS: Materials and methods: Biopsy samples of maxillary sinus cysts of 92 operated patients aged 18 to 74 years were studied. We used standard staining with hematoxylin and eosin, PAS reaction, and immunohistochemical analysis with monoclonal antibodies to CD68 (macrophages) and CD3 (T- lymphocytes) to determine morphological features and severity of inflammation and PanCK AE1/AE2 antibodies to identify epithelium state. RESULTS: Results: All patients were divided into 2 groups: 29 patients with retention cysts and 63 with lymphagiotatic cysts (pseudocysts), depending on the unilateral or bilateral epithelial lining of the cyst wall. Retention cysts had the bilateral epithelial lining with a saving its function and structure. The thinned connective tissue layer was filled with separate clusters of lymphocytes and macrophages. Lymphagiotatic cysts were characterized by the unilateral epithelium lining of the wall with signs of degeneration, desquamation, and loss of the mucus-forming function. Dense infiltration of the connective tissue layer by inflammatory cells with pronounced expression is observed. CONCLUSION: Conclusions: Immunohistochemical analysis with monoclonal antibodies to CD3 and CD68 demonstrated that the inflammatory infiltrate of pseudocysts is represented by T-lymphocytes and different sizes of macrophages. The inflammatory infiltration of the pseudocyst wall was significantly severe compared to retention cysts.

MORPHOLOGICAL JUSTIFICATION OF THE SIGNIFICANCE OF LUMBAR ARTERIES IN THE PREVENTION OF SPINAL CORD ISCHEMIA IN ATHEROSCLEROTIC LESIONS OF ABDOMINAL AORTA.

OBJECTIVE: The aim: To investigate atherosclerosis of the abdominal part of the aorta and atherosclerosis of the lumbar arteries, aimed at improving surgical tactics during reconstructive interventions on the abdominal part of the aorta in patients with multifocal atherosclerosis. PATIENTS AND METHODS: Materials and methods: 20 autopsies were performed. The macro preparation consisted of the part of the abdominal aorta 1х1 sm taken along with a separated lumbar artery for 1-1,5 sm. Histological cuts were coloured with hematoxylin and eosin. The histochemical research was conducted in order to establish changes in all layers of blood vessels. The immunohistochemical research was carried out along with generally accepted histological methods in 10 cases to determine the morphological vessel wall functional state, connective tissue and smooth muscle components. RESULTS: Results: In all cases there were morphological signs of aortic atherosclerosis with different degrees of damage to the lumen. In none of the analyzed cases did we establish pathomorphological signs of atherosclerosis of the lumbar artery distal to the mouth. In the walls of the lumbar arteries, we noted the preservation of the layered structure, the integrity of the endothelial cells, the normal arrangement of smooth muscle cells. CONCLUSION: Conclusions: It was established that there cannot be the atherosclerotic occlusion of the lumbar artery, since there are no signs of atheromatous lesions in its walls, the structure of all layers is preserved, the endothelial damage is absent, the location and structure of the lining cells is normal.

AN INTEGRATED APPROACH TO THE MORPHOLOGICAL DIAGNOSIS OF DIFFERENT TYPES OF PLEOMORPHIC ADENOMAS OF THE SALIVARY GLAND: LONG-TERM RESEARCH RESULTS.

OBJECTIVE: The aim: To describe an integrated approach to the morphological diagnosis of different types of pleomorphic adenomas of the salivary gland. PATIENTS AND METHODS: Materials and methods: Surgical and biopsy material from 30 patients with pleomorphic adenomas of epithelial, mixed and mesenchymal variants was studied using histological, immunohistochemical, genetic, morphometric and statistical methods. RESULTS: Results: The results of research allowed us to identify methods for determination the pleomorphic adenomas types. The first method requires an immunohistochemical reaction with a monoclonal antibody to human papillomavirus type 16, followed by counting the percentage of positively stained cells in the tumor. Thus, the mesenchymal variant of the tumor is diagnosed when the percentage of positively stained cells is < 40%. In the mixed variant, this indicator is ≥ 40%, but ≤ 70%, and in epithelial variant - > 70%. The second method was based on the multivariate discriminant analysis. Three formulae were derived to determine the tumor types (Fmesenchymal = - 41.03 + 4.96Ð¥1 + 1.11Ð¥2, Fepithelial = - 22.27 + 3.46Ð¥1 + 0.85Ð¥2, Fmixed = - 122.25 + 5.63Ð¥1 + 3.2Ð¥2, here Ð¥1 - number of vessels, Ð¥2 - specific volume of parenchyma). CONCLUSION: Conclusions: The authors identified several methods for determining the histological variants of pleomorphic adenomas. These methods will improve the morphological diagnosis of pleomorphic adenomas variants in the preoperative and postoperative periods.

PATHOMORPHOLOGICAL CHARACTERISTICS OF IMMUNOCOMPLEX RENAL DISEASE IN PATIENTS WITH IMMUNODEFICIENCY VIRUS AND HEPATITIS C VIRUS, RECEIVING ANTIRETROVIRAL THERAPY.

OBJECTIVE: The aim is to verify and describe the morphological substrate of renal impairment in HIV/HCV co-infection among patients receiving ART to assess and predict the morphogenesis of immunocomplex lesions. PATIENTS AND METHODS: Materials and methods: To assess and predict the morphogenesis of immunocomplex renal disease, we examined retrospectively the kidney tissue samples of 15 patients, who died with HIV/HCV co-infection and received ART. Histological, histochemical and immunohistochemical research methods were used. RESULTS: Results: Segmental and diffuse mesangial proliferation with extracellular matrix expansion with glomerular damage ≥50% in 9 (60%) cases, and involving <50% of glomeruli in 5 (33%), with CD68 expression as single cells were detected. In 12 (80%) cases, there was uneven swelling and focal proliferation of endothelial cells with the involvement of 20-50% of the glomeruli, as well as the presence of cellular infiltrates in the lumen of capillary loops in 3 (20%) cases with monomorphic intensity in "+". Sclerotic changes were present in various degrees of severity - from cases of complete glomerulosclerosis with obliteration of the Bowman's lumen to focal and microfocal depressions 8 (55%), sclerosis 10 (66%), hyalinosis 1 (6%), uneven thickening, focal cleft 8 (55%) and perihilar focal sclerosis. These areas were positive for IgG and C1q complement fractions within the "+", "++" intensity. Among the study group, no case of HIV-associated nephropathy was found that coincided with the predicted spectrum of kidney damage for patients in this sample. The described morphological changes were mainly verified as immuno-mediated by HCV. CONCLUSION: Conclusions: A comprehensive morphological study revealed the morphological substrate of kidney damage and its morphogenesis in patients with HIV/HCV co-infection, receiving ART.

MORPHOLOGICAL FEATURES OF CELLULAR INFILTRATION IN THE MUCOSA OF LARGE INTESTINE IN ULCERATIVE COLITIS AND IRRITABLE BOWEL SYNDROME.

OBJECTIVE: The aim is to improve morphological diagnostics, including differential, of UC and IBS, identifying morphological features of cellular infiltration in the mucous membrane ofthe large intestine. PATIENTS AND METHODS: Material and methods: Autopsy and biopsy material - fragments of the mucous membrane of the large intestine was used in this study. All the material was divided into 5 groups. Group 1 included autopsy material from 6 cases, in which no general pathological processes in the gastrointestinal tract were detected during autopsy and microscopic examination. Group 2 included biopsy material from 34 patients with diagnosed UC of the 1st activity degree. Group 3 included the biopsy material of 27 patients with UC of the 2nd degree of activity. Group 4 included biopsy material from 19 patients, diagnosed with UC of the 3rd degree of activity. Group 5 included biopsy material from 82 patients with clinically diagnosed IBS. Histological, morphometrical, immunohistochemical and statistical methods of investigation were used. RESULTS: Results: The mucous membrane of the large intestine in patients with ulcerative colitis of varying degrees of activity, compared with the physiological norm, has pronounced infiltration by plasma cells, T-lymphocytes, B-lymphocytes, macrophages, mast cells, eosinophilic and neutrophilic leukocytes in the superficial parts of the epithelium, crypts,lamina propria. There is also an increase in the number and size of lymphoid follicles in the lamina propria. Predominant cellular elements in the infiltrate are plasma cells, T-lymphocytes, eosinophilic and neutrophilic leukocytes. The growth of ulcerative colitis activity leads to an increase the inflammatory cell infiltration in the mucous membrane of the colon, as evidenced an increase the density of cellular infiltrate; the severity of inflammatory changes in crypts and an increase in the number of crypt abscesses; a decrease the number of cases with focal infiltration in the lamina propria and an increase the number of cases with diffuse infiltration; the spread of inflammatory cell infiltration from the superficial parts of the lamina propria to its deep parts with the subsequent involvement of its entire thickness; an increase the central trends of the indexes of the severity of all cellular infiltration, infiltration by plasma cells, T-lymphocytes, macrophages, neutrophilic leukocytes. The mucous membrane of the large intestine in patients with irritable bowel syndrome has moderately pronounced cellular infiltration in the superficial epithelium andlamina propria, in comparison with the physiological norm. The number and size of lymphoid follicles increase. Inflammatory cell infiltration often spreads to the upper onethird or two thirds of the thickness of the lamina propria, characterized by the presence of plasma cells, T-lymphocytes, B-lymphocytes, macrophages, mast cells, eosinophilic and neutrophilic leukocytes. In this case, plasma cells, T-lymphocytes, mast cells and macrophages dominate. The indexes of the severity of all cellular infiltration, as well as infiltration by plasma cells, T-lymphocytes, B-lymphocytes, macrophages, mast cells, eosinophilic and neutrophilic leukocytes, increases in the mucous membrane of the large intestine in irritable bowel syndrome in comparison with the norm. In the mucous membrane of the large intestine in irritable bowel syndrome compared with ulcerative colitis of varying degrees of activity inflammatory cell infiltration is less pronounced. It often extends to one third or two thirds of the thickness of the lamina propria. There are fewer lymphoid follicles, cryptitis and crypt abscesses are not determined. The indexes of the severity of all cellular infiltration, as well as infiltration by plasma cells, T-lymphocytes, eosinophilic and neutrophilic leukocytes are lower. CONCLUSION: Conclusions: The revealed features of cellular infiltration in the mucous membrane of the large intestine make it possible to improve morphological diagnostics, including differential, of ulcerative colitis of varying degrees of activity and irritable bowel syndrome.

IMMUNOHISTOCHEMICAL FEATURES OF THE EXPRESSION OF HUMAN PAPILLOMA VIRUS TYPE 16 IN PLEOMORPHIC ADENOMAS OF SALIVARY GLAND.

OBJECTIVE: The aim is to reveal the immunohistochemical features of human papilloma virus type 16 expression in various histological variants of pleomorphic adenomas of the salivary gland. PATIENTS AND METHODS: Materials and methods: The material of the study was surgical and biopsy material from 30 patients with pleomorphic adenomas of the salivary glands, among which in 15 cases mesenchymal was detected, in 10 - mixed, in 5 cases - epithelial histological variant, respectively. Immunohistochemical study was performed, using mouse monoclonal antibody to human papilloma virus type 16. Visualization was performed, using an EnVisionTM FLEX detection system. Histological sections of grade III cervical intraepithelial neoplasia (CIN III) were used as a positive control; for a negative control, the procedure was performed without primary antibodies. The immunohistochemical reaction was assessed by a semi-quantitative method by counting the percentage of positively stained cells in the field of view of a microscope × 400. Microspecimens were studied, photoarchived on an Olympus BX-41 microscope. RESULTS: Results: Expression of human papilloma virus type 16 of varying severity was determined in 26 cases of pleomorphic adenomas of the salivary glands, which was 86.7%. The epithelial component of the pleomorphic adenoma of the salivary gland was characterized by a more pronounced expression of the monoclonal antibody to human papilloma virus type 16 compared to the mesenchymal component of the tumor. The severity of the immunohistochemical reaction with a monoclonal antibody to human papilloma virus type 16 depended on the histological variant of the pleomorphic adenoma of the salivary gland. Epithelial, mixed and mesenchymal variants of pleomorphic adenoma of the salivary gland were characterized, respectively, by the most pronounced, pronounced and moderately pronounced expression of a monoclonal antibody to human papilloma virus type 16. CONCLUSION: Conclusions: A comprehensive immunohistochemical study with a monoclonal antibody to human papilloma virus type 16 revealed the presence of a causal relationship between the infection of a patient with human papilloma virus type 16 and development of pleomorphic adenoma of the salivary gland in him.

MORPHOLOGICAL JUSTIFICATION OF THE SALIVARY GLAND TISSUE RESECTION BOUNDARIES DURING SURGICAL TREATMENT OF PATIENTS WITH PLEOMORPHIC ADENOMAS.

OBJECTIVE: The aim is to substantiate morphologically the resection boundaries of the salivary gland tissue in the surgical treatment of patients with pleomorphic adenoma of different histological variants. PATIENTS AND METHODS: Materials and methods: The study used autopsy, surgical and biopsy material, divided into 2 groups. Group 1 included autopsy material (n=6), represented by tissue fragments of the parotid salivary gland, in which macroscopic and microscopic examination did not reveal any general pathological processes. Group 2 included surgical and biopsy material from 30 patients, represented by pleomorphic adenomas with adjacent tissue of the salivary gland at a distance of 0.5 cm and 1.0 cm. Histological, morphometric and statistical research methods were used. RESULTS: Results: The morphological features of the salivary gland tissue which was adjacent to the pleomorphic adenoma at a distance of 1.0 cm, practically corresponded to thephysiological norm. However, the tissue of the salivary gland, bordering the tumor at a distance of 0.5 cm, was characterized by pronounced changes. These changes were: violation of the ratio of the specific volumes of the parenchyma and stroma; atrophy of the terminal sections and ducts with cystic expansion of some ducts; thickening of the secretion and formation of calculi in the lumen of some ducts; atrophic and alterative changes in the epithelial lining the terminal sections and ducts; sclerosis and lipomatosis, areas with hyalinosis and dystrophic calcification in the stroma; hemodynamic disturbances in the stroma with a decrease in the number of vessels; pronounced focal or diffuse immune infiltration in the stroma in some areas with the lymphoid follicles formation. CONCLUSION: Conclusion: The comprehensive study has confirmed that removal of the tumor with the adjacent tissue of the salivary gland at a distance of 1.0 cm in patients with pleomorphic adenoma of various histological variants is the most justified from the morphological point of view.

TUMORS AND TUMOR-LIKE LESIONS OF THE SALIVARY GLANDS: MORPHOLOGICAL CHARACTERISTICS OF THE SURGICAL MATERIAL.

OBJECTIVE: The aim is to give a morphological characteristic of tumors and tumor-like lesions of the salivary glands in the course of a comprehensive analysis of the surgical material. PATIENTS AND METHODS: Materials and methods: The study used surgical material from 67 patients with various pathologies of the salivary glands. The patients were treated at Kyiv City Clinical Hospital No. 12 (Ukraine, Kiev) from 2014 to 2018. The resulting material was fixed in a 10% solution of neutral formalin (pH 7.4) for 24-48 hours, carried out according to the generally accepted technique and embedded in paraffin. Serial sections 2 µm thick were made from paraffin blocks and stained with hematoxylin and eosin. Microspecimens were studied, using Olympus BX-41 microscope (Japan). RESULTS: Results: A comprehensive morphological study of the surgical material of patients with salivary gland pathology undergoing treatment at Kyiv City Clinical Hospital No. 12 (Ukraine, Kiev) for the period from 2014 to 2018 revealed benign tumors and tumor-like lesions of these glands. Pleomorphic adenomas and adenolymphomas represented benign tumors of the salivary glands, while cysts represented tumor-like lesions. Different ratios of parenchymal and stromal components characterized pleomorphic adenomas of the salivary glands. On this basis, we identified three tumor variants (mesenchymal (15 cases, 50.0 %); mixed or classic (10 cases, 33.3 %); epithelial (5 cases, 16.7 %)). A characteristic microscopic feature of salivary gland adenolymphomas was a pronounced predominance of the parenchyma over the stroma. A well-defined wall, represented by connective tissue fibers and epithelial lining, characterized the cysts of the salivary glands. The connective tissue capsule separating the tumor tissue from the intact tissue of the salivary gland was clearly pronounced in adenolymphomas, and in pleomorphic adenomas it could be clearly expressed, intact, with tumor invasion or absent. In mesenchymal and mixed variants of pleomorphic adenomas, in comparison with the epithelial variant, there was a frequent tumor invasion of the capsule, thinning of the capsule or its absence. CONCLUSION: Conclusions: Morphological examination of the surgical material allows us to diagnose tumors (pleomorphic adenomas and adenolymphomas) and non-tumor lesions (cysts) of the salivary glands. This, of course, is of great therapeutic, diagnostic and prognostic value. Among the identified pathology of the salivary glands, pleomorphic adenomas cause certain difficulties in morphological diagnosis due to their structural diversity and heterogeneity, sometimes requiring morphometric, immunohistochemical or genetic research.

EXPRESSION FEATURES OF HUMAN PAPILLOMA VIRUS TYPE 16 AND ANTI-EPSTEIN-BARR VIRUS IN PLEOMORPHIC ADENOMA, SURROUNDING AND INTACT SALIVARY GLAND.

OBJECTIVE: The aim is to reveal the expression features of MCA to human papilloma virus type 16 and anti-Epstein-Barr virus in the pleomorphic adenoma, surrounding and intact salivary gland. PATIENTS AND METHODS: Materials and methods: It was used surgical and biopsy material from 30 patients, represented by pleomorphic adenomas with surrounding to tumor tissue of the salivary gland and intact tissue of the salivary gland (the distance between the tumor and the intact salivary gland - 10 mm). Immunohistochemical study was performed using mouse monoclonal antibody (MCA) to human papilloma virus type 16 (clone CAMVIR-1, «Diagnostic BioSystems¼, USA) and anti-Epstein-Barr virus (LMP, clone CS. 1-4, «Dako¼, Denmark). Visualization was performed, using an EnVisionTM FLEX detection system (Dako, Denmark). Antigen unmasking was carried out in citrate buf f er pH 6.0 at 95°C. Primary antibodies were incubated at room temperature for 30 minutes, secondary antibodies - 20 minutes. Sections were counterstained with Gill hematoxylin. We assessed the immunohistochemical reaction by a semi-quantitative method by counting the percentage of positively stained cells in the fi eld of view of a microscope × 400. Microspecimens were studied and photoarchived on an Olympus BX-41 microscope (Japan). RESULTS: Results: In this study it was detected a positive immunohistochemical reaction with MCA to human papilloma virus type 16 and anti-Epstein-Barr virus, respectively, in 26 (86.7%) and 8 (26.7%) cases. Epithelial, mixed and mesenchymal variants of pleomorphic adenoma of the salivary glands are characterized, respectively, by the severely expressed, moderately expressed and minimally expressed of MCA to human papilloma virus type 16 and anti-Epstein-Barr virus. The parenchymal component of pleomorphic adenoma is characterized by more marked expression of these markers as compared to the stromal component. The epithelial cells of the salivary glands, surrounding the pleomorphic adenoma, as well as intact salivary glands, express MCA to human papilloma virus type 16 and anti-Epstein-Barr virus. The severity of the expression of these markers in the salivary gland is determined by the histological variant of the tumor (severely expressed in the epithelial variant, moderately expressed in the mixed variant, and minimally expressed in the mesenchymal variant). CONCLUSION: Conclusions: The immunohistochemical study has shown that the Epstein-Barr virus and, especially, human papilloma virus type 16 can act as exogenous trigger factors involved in the development of pleomorphic adenoma of the salivary glands. The revealed immunohistochemical features of MCA expression to human papilloma virus type 16 and anti-Epstein-Barr virus in the salivary gland surrounding the pleomorphic adenoma and in the intact tissue of the salivary gland make it possible to recommend the extracapsular dissection of the tumor with resection of the adjacent intact tissue of the salivary gland at a distance of 10 mm in patients with pleomorphic adenoma.

CLINICAL AND MORPHOLOGICAL CORRELATION DEPENDENCIES AND THEIR SIGNIFICANCE IN PATIENTS WITH COMPLICATIONS OF LABORED ERUPTION OF THE LOWER THIRD MOLARS.

OBJECTIVE: The aim is to determine the clinical and morphological dependencies, which are important for diagnostics, treatment and prediction of outcomes of pathological processes in the region of the LTM with complicated eruption, as based on the study of histopathological changes of paradental tissue (mucous membrane, walls of retromolar pocket, alveolar bone tissue). PATIENTS AND METHODS: Materials and methods: The materials of the study were 34 biopsy specimens of pathologically altered soft tissue and parodontium obtained as a result of pericoronectomy, extraction of the LTM and other surgical interferences performed based on the relevant indications in 28 patients in the region of the LTM with complicated eruption. Morphological and statistical research methods were used. RESULTS: Results: The local pathological processes, which chronologically precede the destructive changes in the hard tissue of a tooth (caries), are developed in patients of both genders with complicated LTM eruption in soft tissue of parodontium and the adjacent bone tissue of the alveolar wall in the majority of cases. As per biopsy examinations, the frequency of the main pathological processes in paradental tissue in case of complicated LTM eruption varies from 25 to 60 % of the number of biopsy specimens and occurs in various combinations in patients with different values of clinical parameters. The correlation relationships between the patients' clinical data and the morphological parameters of damage to paradental tissue are weak, multidirectional and uncertain in the majority of combinations (considering the available number of biopsy specimens studied). The close certain positive dependence between the damage of the squamous epithelium and the inflammation activity in the lamina propria mucosae, covering the tooth: in the vast majority of cases, the presence of damaged epithelium (within the biopsy specimen) is associated with the inflammation of high activity, was established as based on correlation relationships between the morphological parameters of damage to paradental tissue. CONCLUSION: Conclusions: The found pathological changes and the correlations justify surgical tactics on paradental soft and osseous tissues that are directed on the LTM sparing.

MALIGNANT TUMORS OF THE APPENDIX: CLINICAL AND MORPHOLOGICAL ANALYSIS OF CASES FROM THE PRACTICE.

The authors have analyzed medical histories of two patients, treated in health care facilities of Kharkiv region from 2008 to 2020. These patients underwent urgent appendectomy, given the existing clinic of acute appendicitis. Morphological examination of the surgical material allowed us to diagnose adenocarcinoma in one case, and neuroendocrine tumor in combination with endometriosis in the other case. Morphological examination of the surgical material in the first case revealed a moderately differentiated adenocarcinoma and diffuse neutrophilic infiltration in all layers of the appendix, and in the second case - a well-differentiated neuroendocrine tumor (G3), combined with the signs of phlegmonous-ulcerative appendicitis and loci of endometriosis. In both cases, there were no specific for the oncological process anamnestic and clinical-instrumental data, and these tumors were manifested by the clinic of acute appendicitis. Only morphological examination of the surgical material allowed identifying the pathological process. Clinical and morphological analysis of cases from the practice of malignant tumors of the appendix (neuroendocrine tumor and adenocarcinoma) will be useful and interesting for the medical community and should stimulate cancer vigilance in physicians.

Substantiation of diagnosis and treatment of chronic recurrent aphthous stomatitis in crohn's disease.

OBJECTIVE: The aim: To substantiate the diagnosis and treatment of chronic recurrent aphthous stomatitis in Crohn's disease. PATIENTS AND METHODS: Materials and methods: The analysis of diagnostic and treatment of 52 patients with chronic recurrent aphthous stomatitis in Crohn's disease (main group), mean age 31.8 + 2.3 was performed. The comparison group consisted of 50 patients with chronic recurrent aphthous stomatitis not associated with Crohn's disease (mean age 34.7 + 1.8). Patients in both groups were studied for clinical manifestations, morphological and immunohistochemical studies the aphthae on the oral mucosa were performed. RESULTS: Results: An objective evaluation of the oral mucosa showed that the aphthae on the oral mucosa in patients of both groups did not differ visually. In the morphological study, the patients in the main group had granulomatous inflammation of the oral mucosa, characteristic of Crohn's disease, while the patients in the comparison group had fibrinous inflammation. Immunohistochemical study of the cell infiltrate phenotype in the area of the lesion revealed that the patients in the main group there prevailed CD68+macrophages, the appearance of both intraepithelial and cell infiltrates of T-lymphocyte suppressors, which is characteristic of Crohn's disease. CONCLUSION: Conclusions: Diagnosis of chronic recurrent aphthous stomatitis in Crohn's disease is based on biopsy of the aphthae on the oral mucosa and their morphological examination, the results of which confirm the presence of granulomatous inflammation, with a large number of macrophages, the presence of T-lymphocytes, characteristic of Crohn's disease, while recurrent aphthous stomatitis of another genesis morphologically detect fibrinous inflammation. The choice of therapeutic tactics for chronic recurrent aphthous stomatitis depends on the results of the morphological study. When granulomatous inflammation is detected in patients with chronic recurrent aphthous stomatitis, which is characteristic of Crohn's disease, in addition to topical treatment of the oral mucosa, specific therapy with mesalazine drugs is prescribed.

MORPHOLOGICAL CHARACTERISTICS OF PLEOMORPHIC ADENOMAS OF SALIVARY GLANDS (ANALYSIS OF THE SURGICAL MATERIAL).

OBJECTIVE: The aim of the study is to reveal the morphological features of pleomorphic adenomas of the salivary glands during a comprehensive examination of the surgical material. PATIENTS AND METHODS: Materials and methods: Surgical material from 30 patients with pleomorphic adenomas of the salivary glands was studied. Microspecimens stained with hematoxylin and eosin were studied, using an Olympus BX-41 microscope (Japan) with subsequent processing with the Olympus DP-soft version 3.1 software, which was used to conduct a morphometric study. By morphometry in the tumor tissue, the specific volumes of the parenchyma and stroma, the thickness of the capsule located between the tumor tissue and the tissue of the salivary gland were determined; the absolute number of vessels in the field of view of the microscope was counted at × 100 magnification. RESULTS: Results: Comprehensive morphological analysis of the surgical material of removed neoplasms of the salivary glands has showed that mesenchymal (15 cases, 50.0%) and mixed (10 cases, 33.3%) variants of pleomorphic adenomas are more common, and less often epithelial variants (5 cases, 16.7%). Pleomorphic adenoma is characterized by a different ratio of the epithelial (parenchymal) and mesenchymal (stromal) components forming this tumor, structural diversity and heterogeneity of the structure of these components, which do not have clear boundaries and are mixed with each other. A characteristic feature of pleomorphic adenoma is also the combination in each case of different types of epithelial cells and the structures that they form, as well as areas of various differentiation of the mesenchymal component. Mesenchymal and mixed variants of pleomorphic adenomas, in comparison with the epithelial variant, are more prone to progression and recurrence, as evidenced by our identified active processes of angiogenesis in tumor tissue, frequent tumor invasion of the capsule, thinning of the capsule or the absence of the capsule, less pronounced infiltration of the capsule by immune cells. CONCLUSION: Conclusions: The morphological features of mesenchymal, mixed and epithelial variants of pleomorphic adenomas of the salivary glands revealed by the authors should be takeninto account by clinicians during choosing the tactics for treating the patient, which will undoubtedly help to reduce the incidence of tumor malignization and its recurrence.

Pathomorphological characteristics and immunohistochemical features of placentae from hiv-positive pregnant women with fetal growth retardation.

OBJECTIVE: The aim: To study the pathomorphological characteristics and immunohistochemical features of placentae from human immunodeficiency virus-positive (HIV-positive) pregnant women with FGR. PATIENTS AND METHODS: Materials and methods: The study material was 32 placentae, including 12 placentae from HIV-positive pregnant women with FGR (study group), 10 placentae from HIVpositivepregnant women without FGR (comparison group) and 10 placentae from HIV-negative women with physiological pregnancy (control group). An immunohistochemical study was performed using monoclonal antibodies (MCA) against CD31+ and vascular endothelial growth factor (VEGF). RESULTS: Results: Pathomorphologic changes of the placentae from HIV-positive pregnant women with FGR were characterized by edema in the umbilical cord tissue, partial dissection of the vascular wall fibers, dysmucoidosis; intracellular edema and hemorrhage in the fetal membrane tissues. In the placentae tissue it was found marked manifestations of degenerative changes in the form of the areas of fibrinoid necrosis, pronounced manifestations of dysmucoidosis, vacuolation of the villi stroma, an increase in the number of avascular villi and immature villi of small caliber with the phenomena of syncytiotrophoblast focal hyperplasia. An immunohistochemical study with MCA against CD31+ revealed the expression (optical density) of the vascular endothelial cells up to 2 points, and the expression level up to 3 points in the isolated areas with the appearance of the expression on the villi surface and in their thickness. During immunohistochemical studies with VEGF the expression level and its optical density increased up to 2-3 points, in some areas the expression of deposits were detected on the villi surface, in their thickness and in the intervillous space. CONCLUSION: Conclusions: The comparative pathomorphological and immunohistochemical study of the placentae demonstrated more significant changes in the group of HIV-positive pregnant women with FGR. In the placentae of HIV-positive pregnant women with FGR immunohistochemical examinations revealed a high level of CD31+ and VEGF expression.

Clinical and morphological features of the ovarian brenner tumour: current state of the problem.

OBJECTIVE: Introduction: Ovarian tumours are an actual problem of present-day medicine, being one of the most difficult sections of modern oncology. The majority of ovarian tumours are of epithelial origin. The ovarian Brenner tumour represents a rare epithelial ovarian neoplasm and accounts for 1-2% of all ovarian neoplasms. The aim of the study is to identify clinical and morphological features of ovarian Brenner tumour. PATIENTS AND METHODS: Materials and methods: The material was 5 cases of Brenner ovarian tumour, diagnosed in the study of 4 cases of operational material and 1 case of autopsy observation for the period from 2007 to 2019. Histological and immunohistochemical staining methods were used. The microspecimens were examined on an Olympus BX-41 microscope (Japan). RESULTS: Results: Ovarian Brenner tumour is a rather rare pathology, the histogenesis of which is debatable. Morphological examination is the main method for its diagnosing. Ovarian Brenner tumours developed in women of middle and old age (the average age was 51.8 years). Women with a malignant ovarian Brenner tumour were older than women with a benign variant (the average age in women with a malignant variant was 55.8 years, with a benign variant - 49.3 years). Benign ovarian Brenner tumour occurred more frequently compared with a malignant one. Malignant and benign variants of ovarian Brenner tumour were characterized by a one-sided nature of the lesion with frequent involvement in the pathological process of the left ovary. Clinically, in patients with a benign variant of the Brenner tumour in all cases an abdominal pain syndrome was determined, combined in one case with metrorrhagia. A malignant ovarian Brenner tumour was clinically manifested by severe abdominal pain syndrome, combined in one case with complaints of an increase in the size of the abdomen, and in another case with intoxication syndrome and a clinic of small bowel obstruction. In all cases a malignant ovarian Brenner tumour metastasized to the omentum and in one case also to the small intestine wall. Macroscopically the ovarian Brenner tumour had the form of a node, the dimensions of which were significantly larger for the malignant variant compared with a benign, dense or soft consistency, on the cross section of a whitish-gray or brown color with cysts. A damaged ovary with a malignant variant of Brenner tumour significantly increased in size, while with a benign one, its size did not change or increased slightly. In all cases the malignant and benign variants of ovarian Brenner tumour were combined with various reproductive system organs pathologies (mucinous papillary cystadenoma of the ovary, serous ovarian cyst, ovarian endometriosis, endometrial hyperplasia, cervical nabothian cysts, uterine leiomyoma). CONCLUSION: Conclusions: A study conducted by the authors revealed clinical and morphological features of a rare ovarian tumour - Brenner tumour, which will contribute to a better understanding of this pathology by the doctors of various specialties, and improve the treatment and diagnostic process.

Clinical and morphological correlations and histopathology of joint damage in patients with diffuse-type tenosynovial giant cell tumor.

OBJECTIVE: Introduction: Tenosynovial giant cell tumor (TSGCT) (synonym - pigmented villonodular synovitis) - is a rare benign proliferative lesion of the synovial sheath, localized in the joint capsule, bursa or tendon sheath and characterized by locally destructive growth. Depending on the prevalence within the joint elements, the presence of a capsule around the tumor, histophotographic features of cell structure and clinical behavior TSGCT can be divided to localized or diffuse type. The aim of the study was researching of histopathological properties of diffuse-type TSGCT, determine the parameters its morphological indicators and to find out the correlation between these morphological and clinical parameters. PATIENTS AND METHODS: Materials and methods: The research material was used biopsy (resect) of pathological lesions from 50 patients who were diagnosed and histologically verified diffuse-type TSGCT. Microscopic examinations of the stained sections and their photo archiving were carried out with use of a Olympus-CX 41 light optical microscope. Group measurable parameters (mean values and Pearson tetrachoric index (association coefficient) were calculated in groups of comparison for morphological and clinical indices of TSGCT. The mean values were compared by Student's test, P value of ≤0.1 was considered statistically significant. RESULTS: Results: Correlation analysis of indicators that accounted for the pairs of cases «clinic - morphology¼ revealed the relationships, that had the highest parameters of the association coefficient between such indicators: «presence of villous growths¼ - «severity of hemosiderosis¼ (if hypertrophied synovial villi available, with vascular injection and pronounced proliferation of synovial cells, there is also a significant accumulation of hemosiderin pigment); «presence of villous growths¼ - «type of predominant cellular proliferates¼ (if cells of TSGCT diffuse type consists of monotonous sheets of stromal cells, with uniform, oval to reniform nuclei, the proliferation of villi in synovial layer is non-distinctive); «presence of nodes¼ - «kind of stroma¼ (if nodes predominate, their histological structure is mainly represented by polymorphic clusters of synovitis cells in the form of cells, strands, chains, solid formations, among immature connective tissue with low hyalinosis); «cell size (area, cm²)¼ - «severity of haemosiderosis¼ and «cell size (area, cm²)¼ - «the number of multinucleated giant cells¼ (there is a pronounced deposition of pigment and accumulation of osteoclast-like multinucleated giant cells type, although usually their number is relatively small compared to the localized type of TSGCT). CONCLUSION: Conclusions: Morphological parameters, that we have identified, characterize pathological changes in the tissues of TSGCT; careful analysis of the frequency of their occurrence in the different comparison groups made it possible to establish intergroup differences and correlations between individual indicators, which were previously unknown or not obvious. Our study was determine to analyze of incidence rates and correlation relationships, revealed some previously unknown differences and dependencies that are important for understanding the pathogenesis, improvement of diagnosis and prognosis of diffuse-type TSGCT.

morphological and immunohistochemical features of tissue homeostasis in patients with alopecia areata in the chronic stage associated with metabolic syndrome and the non-burdened course of the disease.

OBJECTIVE: Introduction: Alopecia areata (AA) is a tissue-specific disease of the hair follicles, manifested by foci of baldness on the head and other areas of the skin. The aim of the study was to identify the tissue homeostasis state on the basis of pathomorphological and immunohistochemical changes taking into account the features of Ki67, bcl-2, caspase-3, and CD31 expression in patients with AA in the chronic stage associated with metabolic syndrome and the non-burdened course of the disease. PATIENTS AND METHODS: Materials and methods: Pathomorphological and immunohistochemical studies of Ki67, bcl-2, caspase-3, and CD31 expression in biopsies specimens from skin lesions in the chronic stage of the disease were performed in 11 patients with AA associated with metabolic syndrome and the non-burdened course of the disease. RESULTS: Results: The results of complex morphological study showed that in skin biopsies of patients with AA with metabolic disorders pathomorphological changes were more affected both in the epidermis and skin appendages - degenerative changes in the epithelium, in the dermis, manifestations of appendage atrophy and stromal fibrosis. In patients with AA without metabolic disorders the proliferative potential of epithelial cells (Ki67 proliferation index) was 20-25%, in cases of AA with metabolic syndrome - 5-10%, indicating a decrease in regenerative capacity of the tissue. The state of the microcirculatory bed (CD31) in cases of AA without metabolic disorders is more favorable for the trophic tissue function and decreases in the group of AA with metabolic disorders. It was found that activation of pathological cell apoptosis was observed in cases of AA with metabolic disorders and lower level of bcl-2 expression. In our observations, the level of expression of caspase-3 was at a relatively high level, indicating the activation of pathological apoptosis in the tissues of the affected areas. CONCLUSION: Conclusions: Our pathomorphological, immunohistochemical data allows us to assert that it is advisable to carry out a biopsy of the affected areas with the establishment of levels of proliferative activity of epithelial and stroma cells, the state of the microcirculatory vessels, the possibilities of repair of the affected areas, assessment of the level of apoptosis in order to predict the course of the disease and usage of the personified approach to treatment.

Development of obliteration in the great saphenous vein after influence of high-frequency endovenous welding by data of morphological and ultrasonic studies

Introduction: Acute ascending thrombophlebitis (AAT) of the great saphenous vein (GSV) is one of the problems in modern surgery. The aim: Study of morphological and ultrasonic changes in a thrombosed vein following the influence of high-frequency endovenous electrical welding and assessment of the efficacy of application of this method to treatment of acute ascending thrombophlebitis. Material and methods: During the period of 2016-2018, surgery departments of Kyiv City Hospital No. 8 provided surgical treatment for 52 male and female patients with AAT of the GSV, who underwent high-frequency endovenous electrical welding (EVEW) with help of an EK300M Svarmed apparatus. The patients' age ranged from 19 to 78 years (their mean age was 51±2.63 years). According to the international CEAP (сlinical-etiological-anatomical-pathophysiological) classification, C2 was revealed in 4 cases, C3 in 19, C4 in 13, C5 in 9 and C6 in 7. Sections, prepared in compliance with standard methods, were morphologically examined. Photo archiving was made with use of a ZEISS light optical microscope (Germany) and «Axio Imager. A2¼ data processing system. Duplex ultrasonography (DUS) was performed with help of a TOSHIBA Nemio XG (Japan) device, equipped with a convex transducer having the working frequency of 3.5-5 MC and a linear transducer at a range of 7.5-12 MC. Ultrasonic studies were carried out 2-7 days after the operation. Remote results were assessed after 3, 6 and 12 months. Results: Morphological examinations of vein preparations after EVEW with standard haematoxylin-eosin staining revealed homogenization of thrombotic masses in the venous lumen and a close relationship of the veins with the treated vascular wall; in the majority of examined cases, thrombotic masses totally obliterated the venous lumen. All the layers of the venous wall ­ internal, middle and external ­ coalesced into a single homogenous complex. Specific staining on elastic fibers revealed their total destruction in the internal and middle coats, thinning and fragmentation of elastic fibers in the adventitia. Total occlusion of the GSV was observed sonographically in 49 of 52 cases (94.24%) on days 2-7 after the influence of EVEW. Within 3-6 months, 3 cases (5.76%) developed some partial recanalization. During 9-12 months, colour mapping revealed preservation of some partial and haemodynamically insignificant recanalization in 2 cases (3.84%). One case (1.92%) developed the complete and haemodynamically significant recanalization of the whole welded segment of GSV. Conclusions: Analysis of ultrasonic studies showed that despite the total destruction of the whole venous wall during the first days after the influence of EVEW there were areas of parietal blood flow in 5.76% of cases. During a remote period of follow-up from 3 to 6 months the above changes could develop partial and haemodynamically insignificant recanalization in 3.84% of cases. Within the period of follow-up from 9 to 12 months those areas of blood flow could lead to the complete and haemodynamically significant recanalization of the welded GSV in 1.92% of cases. High-frequency EVEW of the thrombosed GSV in AAT caused the total destruction of thrombotic masses and all layers of the venous wall and made it possible to achieve the total obliteration of the welded vein in 94.24 % of cases.

[Genetic-morphological peculiarities of response to standard therapy in patients with dyshidrotic eczema of palms and soles].

OBJECTIVE: Introduction: Dyshidrotic eczema of palms and soles (DEPS) is an inflammatory skin disorder that has a multifactorial nature and is characterized by the development of vesical elements with the histological picture of spongiosis and development of intraepidermal vesicles. The aim: Establishment of the features of pathomorphological changes of the epidermis and dermis in patients with manifestations of dyshidrotic lesions of palms and soles with different genotypic variants of the C646G of the NR3C1 gene before treatment based on the study of skin biopsies taking into account the response to standard therapy. PATIENTS AND METHODS: Materials and methods: In 57 patients with dyshidrotic lesions, a pathomorphological and immunohistochemical examination of biopsy specimens from a lesion focus of the skin were carried out and a genetic examination was carried out to determine the polymorphic variant C646G of the NR3C1 gene. RESULTS: Results: The results of this study in patients with DEPS showed that in patients with genotype 646 CC, which are torpid to treatment, there is a complex of immune defense with the activation of complement system with activation of C3 and C4d. The activity of expression of CD4 + cells indicating the intensity of the inflammatory response compared with patients with the 646 CC genotype, which were sensitive to treatment. In cases of 646 CG genotypes which were sensitive to topical treatment with steroid, there was a slight decrease in C3 and a decrease in C4d. There was no change in the activation of CD4 + lymphocytes compared with insensitive patients with genotype 646 CG. Moreover, in determining the prognosis and choosing treatment tactics, of great practical value is the presence of immunological parameters that were revealed by the immunohistochemical examinations and were determined by the genotypic peculiarities in patients with DEPS. CONCLUSION: Conclusions: Integral evaluation of the pathomorphological study of biopsy dyshidrotic lesions of sensitive and insensitive patients with different genotypic variants of the C646G of the NR3C1 gene before treatment allows obtaining objective information on the direct effect of glucocorticosteroid therapy. According to the results of our study, the association between NR3C1 gene variants, the pathomorphological features and degree of healing of dyshidrotic lesions of palms and soles was established: the polymorphic version of 646 CC in insensitive patients was associated with additional complement activation of the complement of fractions of C3 and C4d in comparison with sensitive patients of this genotype; рolymorphic variants of 646 CG in sensitive patients - with a slight decrease in the deposition of complement fractions of C3 and C4d іn comparison with insensitive patients of the corresponding genotype.