[Modern view on the problem of diagnostics of renal angiomioadenomatous tumor].

INTRODUCTION: Angiomyoadenomatous tumor as a nosological entity is not included in the latest version of the International Histological Classification of Kidney Tumors (WHO, 2022) and is related to provisional entity. Currently, there is no consensus among researchers about the nosological affiliation of an angiomyoadenomatous tumor. AIM: To comparatively analyze the histological, immunophenotypic, ultrastructural and molecular parameters of renal angiomyoadenomatous tumor and clear cell papillary renal cell tumor. MATERIALS AND METHODS: The study was performed on surgical specimen from 5 and 10 patients with renal angiomyoadenomatous tumor and with clear cell papillary renal cell tumor, respectively. Immunohistochemical study was carried out on paraffin sections according to the standard protocol. Antibodies HMWCK, AE1/AE3, 7, E-Cadherin, EMA, PAX8 and 9 were chosen. To study tumor tissues on semi-thin and ultra-thin sections, an electron microscope Philips TECNAI 12 BioTwinD-265 was used. For in situ fluorescent diagnostic detection, defined centromere probes, LSI 13/21, LSI N25 /LSI ARSA, TelVysion telomeric probe and a two-color VHL/CEP3 probe were used. RESULTS: Angiomyoadenomatous tumor is characterized by a three-phase structure. In contrast to clear cell papillary renal cell tumor, angiomyoadenomatous tumors show complete membranous expression of CA9. CONCLUSION: Our results allow to state that angiomyoadenomatous tumor and clear cell papillary renal cell tumor are different neoplasms.

[Exosomes' role in intercellular interactions in different variants of lung injury in fatal cases of COVID-19]. / Rol' ekzosom v mezhkletochnykh vzaimodeistviyakh pri razlichnykh variantakh porazheniya legkikh v letal'nykh sluchayakh COVID-19.

BACKGROUND: Extracellular vesicles are surrounded by a phospholipid bilayer, carrying various active biomolecules and participating in many physiological and pathological processes, including infectious ones. OBJECTIVE: To research the role of exosomes in intercellular interactions in the pathogenesis of various types of lung damage in fatal cases of COVID-19. MATERIAL AND METHODS: We conducted a clinical and morphological analysis of 118 fatal cases caused by coronavirus infection in Moscow. We selected 32 cases with morphological signs of various types of lung lesions for immunohistochemical reaction (IHC) with antibodies against tetraspanin proteins (CD63, CD81), which are involved in the assembly of exosomes, as well as with antibodies against viral proteins: nucleocapsid and spike protein. We determined the main producing cells of extracellular vesicles and cells containing viral proteins, carried out their comparison and quantitative analysis. RESULTS: IHC reaction with antibodies against CD63 showed cytoplasmic granular uniform and subapical staining of cells, as well as granular extracellular staining. We determined similar staining using antibodies against viral proteins. Extracellular vesicles were found in the same cells as viral proteins. The main producing cells of vesicles and cells containing viral proteins were found to be macrophages, type II pneumocytes, and endothelial cells. CONCLUSION: Taking into account the results of the literature, the localization of viral proteins and extracellular vesicles in the same cells indicates the key role of vesicles in the pathogenesis of various forms of lung damage by the SARS-CoV-2 virus, in the dissemination of the pathogen in the organism, which leads to interaction with the adaptive immune system and the formation of immunity.

[Long-term treatment of morphologically verified myocarditis: successes and probable errors. Case report].

Diagnosis and treatment of myocarditis can be challenging, including determining indications for heart transplantation. We present a 6-year medical history of a 54 years old patient with severe morphologically verified viral-negative lymphocytic myocarditis and systemic manifestations (onset of hemorrhagic vasculitis) combined with moderate coronary atherosclerosis, which regressed according to repeated coronary angiography. For 5 years, the patient received immunosuppressive therapy with methylprednisolone and azathioprine with a significant improvement. Repeated relapses of atrial fibrillation required correction of basic therapy and plasmapheresis. The disease was complicated by thyrotoxicosis and multi-organ dysfunction; the autopsy showed persistent myocarditis activity. The myocarditis is a chronic condition and requires a review of the treatment strategy at each stage.

[SARS-CoV-2-induced non-bacterial endomyocarditis with the development of acquired heart defects]. / SARS-CoV-2-indutsirovannyi nebakterial'nyi endomiokardit s razvitiem priobretennykh porokov serdtsa.

Patients with damage of the mitral, aortic and tricuspid valves and systolic myocardial dysfunction associated with previous SARS-CoV-2 infection are described. The diagnosis of acquired defect was established in 4 patients based on medical history, electrocardiography, echocardiography, magnetic resonance imaging of the heart, endomyocardial or intraoperative myocardial biopsy, and in one case, autopsy. The study of the myocardium included H&E, Van Gieson staining, immunohistochemical (IHC) study with antibodies to CD3, CD20, CD45, CD68, to the nucleocapsid and Spike proteins of SARS-CoV-2. Previous valve diseases (prolapse, bicuspid aortic valve) served as a background for the development of the defect in 2 patients. In all cases, IHC studies revealed coronavirus proteins, lymphocytic endocarditis and myocarditis, moderate fibrosis, and signs of connective tissue disorganization. High titers of anticardiac antibodies indicated an autoimmune mechanism for carditis. No signs of infective endocarditis or thromboembolic complications were identified in any case. In patients with an unclear nature of valvular heart defects, a previous new coronavirus infection should be identified and taken into account as a possible etiological factor. The simultaneous development of lymphocytic myocarditis significantly increases the risk of surgical intervention on the valves and requires an integrated approach to treatment.

[Morphological and molecular portrait hybrid renal tumors].

A hybrid tumor is not officially included in the latest International Histological Classification of Kidney Tumors (WHO, 2022), however, according to the literature, a number of researchers still consider a hybrid tumor as an independent nosological unit. In this regard, the development of morphological and molecular genetic criteria for a hybrid tumor, today, is the main task in the differential diagnosis of oncocytic renal tumors. AIM: Our aim was to carry out to identify immunohistochemical, ultrastructural features and determine the molecular profile of hybrid renal tumors. PATIENTS AND METHODS: The study was performed on the surgical material of 12 patients with a hybrid tumor of the kidney. Immunohistochemical study was carried out on paraffin sections according to the standard protocol. Antibodies CK7, CD117, Cyclin D1, EpCAM, Caveolin1, EABA, and S100A1 were used. To study tumor tissues on semi-thin and ultra-thin sections, an electron microscope Philips TECNAI 12 BioTwinD-265 is used. For in situ fluorescent diagnostic detection, defined centromere probes, LSI 13/21, LSI N25 /LSI ARSA and TelVysion telomeric probe. RESULTS: In some cases, a hybrid tumor is represented by a solid structure of monomorphic oxyphilic cells with a characteristic immuno-, ultraphenotype and molecular profile. CONCLUSION: The results of a comprehensive study confirm that the hybrid tumor is an intermediate link in the process of malignant transformation of oncocytoma into chromophobe renal cell carcinoma.

[The role of expression of monocarboxylates of the first and fourth types (MCT1, MCT4) by tumor and stromal cells of prostate cancer in determining the prognosis and the efficiency of definitive treatment].

AIM: A search for new methods for diagnosing clinically significant prostate cancer is of importance due to the insufficient accuracy of modern methods in detecting aggressive tumors. One of the promising opportunities for the early diagnosis of clinically significant prostate cancer is the assessment of the glycolytic profile of the tumor by determining the expression of monocarboxylates (MCT) types 1 and 4 in tumor cells, as well as in adjacent stromal cells. MATERIALS AND METHODS: An analysis of patients of who underwent radical prostatectomy at the Institute of Urology and Reproductive Health of Sechenov University from 2015 to 2017 was carried out. The patients with histologically confirmed prostate adenocarcinoma were included in the study. Among them, the presence or absence of biochemical recurrence during the first year was studied. An immunohistochemical (IHC) study of postoperative specimen was performed to determine the expression of MCT1 and MCT4 by tumor and stromal cells. The correlation between the intensity of their expression and the risk of biochemical recurrence and the tumor characteristics was evaluated. RESULTS: High membrane expression of MCT1 directly correlated with high stromal expression of MCT4 (r=0.314, p<0.003). A significant direct correlation was found between the predominance of stromal expression of MCT4 over membrane expression and biochemical recurrence (r=0.403, p<0.001), as well as a high ISUP group (4 and 5) (r=0.294, p=0.005). CONCLUSIONS: Determination of the level of expression of type 1 and 4 monocarboxylate transporters in adenocarcinoma cells and tumor stromal cells can become an effective tool for risk stratification, and may also predict the biological behaviors of the prostate cancer and the efficiency of definitive treatment.

[Adenocarcinoma of the lung against the background of usual interstitial pneumonia]. / Adenokartsinoma legkogo na fone obychnoi interstitsial'noi pnevmonii.

Lung adenocarcinoma against the background of idiopathic pulmonary fibrosis according to the world literature ranges from 2.7% to 48%, the incidence increases every year after the diagnosis of idiopathic pulmonary fibrosis. We present a clinical and morphological analysis of an autopsy observation of lung adenocarcinoma that developed against the background of corticosteroid-treated usual interstitial pneumonia in a 78-year-old woman. According to the results of histological and immunohistochemical studies, the diagnosis was formulated as: multicentric non-mucinous invasive adenocarcinoma of the right and left lungs with a lepidic growth pattern with background of usual interstitial pneumonia.

[Immunohistochemical signs of IgG4-related disease in patients with inflammatory bowel diseases]. / Immunogistokhimicheskie priznaki IgG4-svyazannogo zabolevaniya u patsientov s vospalitel'nymi zabolevaniyami kishechnika.

OBJECTIVE: To determine immunohistochemical features of IgG4-related disease in patients with inflammatory bowel diseases (IBD). MATERIAL AND METHODS: Immunohistochemical testing of colonic biopsy material from 35 patients with IBD (24 cases of ulcerative colitis and 11 cases of Crohn's disease) was carried out using IgG, IgG4 and CD138 antibodies. The number of IgG4- and CD138-positive cells was counted in high power field of microscope (×400). Patient selection was random. RESULTS: IgG4-positive cells were detected in the colonic mucosa of 5 patients with ulcerative colitis. The age of the patients ranged from 24 to 47 years. Two patients had a total, and three had a left-sided lesion of the colon. The anamnesis of the disease ranged from 3 to 13 years. The number of positively stained cells in the reaction with the antibody to IgG4 varied from 2 to 50 in high power field of microscope. We were able to detect over 10 IgG4-positive cells in 3 females aged 28, 30 and 31 years with a long history of ulcerative colitis (5, 4 and 3 years, respectively). Two patients had a total lesion of the colon, all three had an exacerbation of the disease, and a morphological study revealed chronic diffuse active erosive colitis. A high degree of histological activity and pronounced diffuse basal plasmacytosis were noted. In one of the cases, the infiltrate captured the muscular lamina of the mucosa and areas of the submucosa. CONCLUSIONS: IgG4-positive cells in the inflammatory infiltrate, including those with an excess of more than 10 in the field of view of the microscope at high magnification, can be observed in patients with ulcerative colitis with severe and prolonged course of the disease. To classify this colitis as a manifestation of an IgG4-related disease, the results of immunohistochemical studies alone are not enough. It is required to accumulate a larger number of observations, as well as to search for other diagnostic criteria for an IgG4-related disease in these patients.

[Modern molecular-genetic aspects of histological variants of renal cell carcinoma].

The article presents the main molecular mechanisms of the pathogenesis of renal cell carcinoma. The molecular pathways that determine the development of histological variants of renal cell carcinoma and the role of stem cells markers in the carcinogenesis of these tumors are considered.

[Assessment of histologic activity in colitis]. / Otsenka gistologicheskoi aktivnosti kolitov.

The histological activity of the bowel inflammation is an extremely important morphological criterion that is encountered in the diagnosis of colitis. However, the determining of its degree is subjective and still does not have a generally accepted principle of gradation. The article describes the most common scale-schemes for assessing the severity of colitis, that include the degree of microscopic changes. The results of the analysis of the of histological activity degree on the material of colonobioptates in colitis of various etiologies (467 patients) are presented. It has been shown that the Geboes scale of ulcerative colitis can be used to assess histological activity in all forms of colitis. The histological features of inflammation should be reflected in the pathological diagnosis and are essential for clinical decision making. This index allows for a comparative analysis of clinical, endoscopic and morphological parameters and better control of the patient's condition during the treatment.

[Ultrastructural features of histological variants of renal cell carcinoma].

The article presents the main electron microscopic signs of the main histological variants of renal cell carcinoma. The ultrastructural profiles of rare forms of renal cell carcinoma included in the latest International Histological Classification of Kidney Tumors (WHO, 2016) are considered.

[A new look at colonic mucosal structural rearrangement and the stages of chronic colitis]. / Novyi vzglyad na strukturnuyu perestroiku slizistoi obolochki tolstoi kishki i stadii khronicheskogo kolita pri vospalitel'nykh zabolevaniyakh kishechnika.

OBJECTIVE: To revise the existing criteria to improve the definition of chronic colitis stages in inflammatory bowel diseases (IBDs). MATERIAL AND METHODS: A total of 100 cases of IBDs (ulcerative colitis (n=70) and Crohn's disease (n=30) diagnosed in 2017 to 2019 were examined. Thirty patients with colitis were selected for a comparison group, who were assigned to an infective colitis group or a drug-induced colitis one at the final diagnosis. RESULTS: The sequence of chronic colitis stages was defined from Stage 1 (early changes) to Stage 3, which are characterized by progressive mucosal structural rearrangement. Mainly at Stage 3 that characterizes the final stage of structural rearrangement in the mucous membrane, where dysplastic changes (the onset of tumor transformation) are detected. CONCLUSION: For the diagnosis of chronic colitis in IBD, it is mandatory to detect mucosal structural rearrangement. Stages 1 and 2 are characterized by early structural changes in the mucous membrane, whereas the process becomes irreversible at Stage 3. The identification of colitis stages is of diagnostic and, undoubtedly, prognostic value.

Subacute and chronic post-covid myoendocarditis: clinical presentation, role of coronavirus persistence and autoimmune mechanisms.

Aim    To study clinical features of myoendocarditis and its possible mechanisms, including persistence of SARS-Cov-2 in the myocardium, in the long-term period following COVID-19.Material and methods    This cohort, prospective study included 15 patients aged 47.8±13.4 years (8 men) with post-COVID myocarditis. The COVID-19 diagnosis was confirmed for all patients. Median time to seeking medical care after COVID-19 was 4 [3; 7] months. The diagnosis of myocarditis was confirmed by magnetic resonance imaging (MRI) of the heart (n=10) and by endomyocardial biopsy of the right ventricle (n=6). The virus was detected in the myocardium with PCR; immunohistochemical (IHC) study with antibody to SARS-Cov-2 was performed; anticardiac antibody level was measured; and echocardiography and Holter monitoring were performed. Hemodynamically significant coronary atherosclerosis was excluded for all patients older than 40 years.Results    All patients showed a clear connection between the emergence or exacerbation of cardiac symptoms and COVID-19. 11 patients did not have any signs of heart disease before COVID-19; 4 patients had previously had moderate arrhythmia or heart failure (HF) without myocarditis. Symptoms of myocarditis emerged at 1-5 months following COVID-19. MRI revealed typical late gadolinium accumulation, signs of hyperemia, and one case of edema. The level of anticardiac antibodies was increased 3-4 times in 73 % больных. Two major clinical variants of post-COVID myocarditis were observed. 1. Arrhythmic (n=6), with newly developed extrasystole or atrial fibrillation without systolic dysfunction. 2. Decompensated variant with systolic dysfunction and biventricular HF (n=9). Mean left ventricular ejection fraction was 34.1±7.8 %, and left ventricular end-diastolic dimension was 5.8±0.7 cm. In one case, myocarditis was associated with signs of IgG4­negative aortitis. SARS-Cov-2 RNA was found in 5 of 6 biopsy samples of the myocardium. The longest duration of SARS-Cov-2 persistence in the myocardium was 9 months following COVID-19. By using antibody to the Spike antigen and nucleocapsid, SARS-Cov-2 was detected in cardiomyocytes, endothelium, and macrophages. Five patients were diagnosed with lymphocytic myocarditis; one with giant-cell myocarditis; three patients had signs of endocarditis (infectious, lymphocytic with mural thrombosis).Conclusion    Subacute/chronic post-COVID myocarditis with isolated arrhythmias or systolic dysfunction is characterized by long-term (up to 9 months) persistence of SARS-Cov-2 in the myocardium in combination with a high immune activity. Endocarditis can manifest either as infectious or as nonbacterial thromboendocarditis. A possibility of using corticosteroids and anticoagulants in the treatment of post-COVID myoendocarditis should be studied.

[Primary generalized AL amyloidosis]. / Pervichnyi generalizovannyi AL-amiloidoz.

The paper describes an autopsy observation of a 71-year-old male with primary generalized AL amyloidosis lasting about 4 months after its manifestation to the onset of death from hepatic and renal failure. Total damage to the liver and spleen, as well as amyloid deposits in the kidneys, adrenal glands, and pancreas were noted.

[Сardiac myxoma: challenge in diagnostics. Case report].

Cardiac myxoma is the most common primary benign cardiac tumor (up to 50% of all primary cardiac neoplasms). The implementation of the modern imaging techniques into the clinical practice, particularly, 2D echocardiography, computed tomography and magnetic resonance tomography (MRI) results to the prompt diagnosis of the myxoma. However, the absence of specific clinical features, insufficient awareness of this condition among the physicians along with a rare prevalence, may lead to a misdiagnosis. This case report is notable for the relatively late diagnosis of a giant left atrial myxoma due to a number of circumstances but with successful surgical treatment.

[Microscopic polyangiitis]. / Mikroskopicheskii poliangiit.

The paper describes an autopsy case of a 69-year-old woman with microscopic polyangiitis lasting about 1.5 months despite intensive treatment. She had generalized productive vasculitis, extracapillary productive glomerulonephritis, adult respiratory distress syndrome with focal pneumonia, isolated lung atelectasis, splenic infarction, and toe and finger gangrene. Morphological differences from those of granulomatosis with polyangiitis and Churg-Strauss syndrome are presented.

Morphological and Molecular-Biological Features of Inflammatory and Regeneratory Processes in Peridont Tissues with Periimplantitis and Periodontitis.

A morphological and immunohistochemical study of periodontal tissues was performed in patients with chronic generalized periodontitis who underwent dental implantation. We studied 44 biopsy specimens from 21 patients (13 women and 8 men) aged 35-60 years with a diagnosis of periimplantation mucositis (7 patients), periimplantitis (8 patients), and severe chronic generalized periodontitis (6 patients). It was established that periimplantitis differs from periimplantation mucositis by a more pronounced inflammatory reaction with a clear predominance of plasma cells in the infiltrate, which captures the fibrous capsule around the implant, destroys it and further spreads to the bone tissue. Based on the immunohistochemical differences in SMA, VEGF, and Ki-67, it is concluded that periimplantation mucositis and periimplantitis are successive stages of progression of the same process. When comparing chronic generalized periodontitis and periimplantitis, the latter shows much more pronounced inflammatory and destructive processes in the area of the implant, due to the addition of immune inflammation, impaired regeneration processes, and destruction of bone tissue.

The exudative-constrictive tuberculosis pericarditis diagnosed by toracoscopic biopsy.

PURPOSE: To present the problems and possibilities of diagnostic and treatment in a patient with resistant exudative-constrictive pericarditis. METHODS: The male patient 31 y. was admitted to the clinic due to exudative pericarditis and arthritis of the left knee joint. His medical history periodic febrile fever with a cough, episodes of syncope and atrial fibrillation, treatment with antibiotics and corticosteroids with a temporary effect. RESULTS: No data were received for systemic disease, hypothyroidism, tumors. With CT in both lungs, small areas of fibrosis and lymphadenopathy were identified. Pericardial sheets diffusely thickened. EchoCG shows one liter of pericardial fluid with fibrin. All tests for viruses and tuberculosis are negative. Thoracoscopy was performed. Morphological examination showed tuberculosis granulomas with caseous necrosis. The growth of mycobacteria of tuberculosis from sputum was obtained. Therapy included pyrazinamide, ethambutol, levofloxacin, prednisolone 20 mg / day. Ponce's disease regressed. Due to the increase of constriction, subtotal pericardectomy was performed. CONCLUSION: Tuberculosis is one of the real causes of pericarditis with massive effusion and an outcome in constriction. The negative results of all laboratory tests for tuberculosis do not exclude the diagnosis. It is necessary to use invasive morphological diagnosis, including thoracoscopic biopsy.

[The morphological characteristics and immunophenotype of renal cell carcinomas with eosinophilic cytoplasm]. / Morfologicheskaia kharakteristika i immunofenotip pochechno-kletochnykh kartsinom s éozinofil'noi tsitoplazmoi.

Eosinophilic cellular renal cell carcinomas embrace a wide range of histological types described in the 2016 WHO International Classification of Kidney Tumors. A variety of histological manifestations associated with the features of tumor morphogenesis in this group poses difficulties in differential diagnosis. AIM: to investigate the morphological and immunophenotypic features of rare types of renal cell carcinomas with eosinophilic cytoplasm. SUBJECTS AND METHODS: An investigation was conducted using a surgical material from 294 patients with a kidney tumor. An immunohistochemical (IHC) study was performed on paraffin sections according to the standard protocol using a wide panel of antibodies. RESULTS: Based on a morphological analysis and IHC study, the tumors were divided into 3 groups: 1) 127 (43%) oncocytic tumors that expressed classical IHC markers for oncocytoma and chromophobe renal cell carcinoma; 2) 50 (17%) oncocytic tumors that did not correspond to the immunophenotypes of oncocytoma and chromophobe renal cell carcinoma; and 3) 117 (40%) eosinophilic cellular nononcocytic renal tumors. CONCLUSION: With the advent of the current differential diagnostic criteria, the classification of renal cell carcinomas continues to expand. To date, a hybrid oncocytic/chromophobic tumor, eosinophilic solid and cystic renal cell carcinoma, and follicular kidney cancer should be regarded as new nosological entities.

[Pathomorphological features of the placentas and the placental sites after in vitro fertilization with a donor egg]. / Patomorfologicheskie osobennosti platsent i platsentarnykh ploshchadok posle ékstrakorporal'nogo oplodotvoreniia s primeneniem donorskoi iaitsekletki.

OBJECTIVE: To identify the structural and immunohistochemical features of the placentas and the placental sites after in vitro fertilization (IVF) with a donor egg (surrogate motherhood). SUBJECT AND METHODS: Morphological and immunohistochemical studies were performed on the placental (a placental disk) and placental bed materials obtained after caesarean delivery. The investigation enrolled 26 patients whose pregnancy occurred with IVF with a donor egg according to the surrogacy (IVF-S) program. A comparison group included 13 patients whose pregnancy occurred after IVF with their own eggs. An immunohistochemical study was conducted on paraffin sections made from biopsy material; mouse antibodies to total cytokeratin (clone AE1/AE3, 'Dako'), HLA-DR (clone TAL.1B5, 'Dako'), and CD138 (clone MI15, 'Dako') were used as primary antibodies. RESULTS: The histological examination of the placentas in the IVF-S group showed the high incidence of central ischemic heart attacks (69%), dissociated cotyledon development (61%), pathological villous immaturity mainly with the predominance of intermediate differentiated villi (46%), and massive perivillous fibrinoid deposition (73%). The obtained differences between with the study and comparison groups were significant (p<0.05). The IVF-S group was characterized by the development of lymphoplasmacytic deciduitis (1.23±0.4 and 0.5±0.3 scores). Examination of the placental site biopsy material in the IVF-S group revealed the following changes: remodeling of the spiral arteries was incomplete in more than 40% of cases, and in 30% of the spiral arteries had no gestational changes. In the comparison group, more than 90% of the spiral arteries were characterized by complete remodeling during pregnancy. There was also an increase in the count of multinucleated trophoblastic giant cells (104.56±4.21 and 65.67±14.45) and HLA-DR positive cells (41.86±5.32 and 29.00±1.87). CONCLUSION: The placentas and the placental sites of the women whose pregnancy occurred with IVF-S are characterized by the development of high lyoplasmacytic deciduitis activity and pronounced placental immune alterations manifested by the high incidence of immune responses at the sites of the closest contact between maternal and fetal tissues. The placental bed exhibited defective spiral artery remodeling, development of chronic inflammatory lesions in the perivascular areas, and an increase in the counts of HLA-DR positive cells and multinucleated trophoblastic giant cells.