[IgG4-related disease of the breast]. / IgG4-svyazannoe zabolevanie molochnoi zhelezy.

IgG4-related disease is an immune-mediated disorder with tumor-like multiorgan involvement, elevated serum IgG4 level and specific histopathological appearance (lymphoplasmacytic infiltrate rich in IgG4+ plasma cells and storiform fibrosis). The article presents rare clinical and morphological observations of IgG4-related mastopathy in women with suspected tumor process. A strategy for the treatment of IgG4-related disease should be based on the results of pre-surgery histopathological examination, which may help to avoid unreasonable surgical intervention and choose glucocorticoids or rituximab as the first-line treatment.

[Causes and mechanisms of sudden cardiac death in children]. / Prichiny i mekhanizmy vnezapnoi serdechnoi smerti u detei.

The paper presents basic morphological criteria of the diagnosis of sudden cardiac death related to different diseases in young people. Attention is drawn to cardiomyopathies, channelopathies, connective tissue dysplasias, Marfan syndrome with cystic medial necrosis, sudden arrhythmic death. Initiating events in sudden cardiac death are discussed. Besides morphological manifestations, the paper dwells upon major genetic events and clinical presentation of the diseases. It is based on both existing publications and own data.

[Heart damage in the combined types of systemic amyloidosis]. / Porazhenie serdtsa pri sochetannykh formakh sistemnogo amiloidoza.

The cardiovascular system is a common target of systemic amyloidosis (SA); amyloid light chain (AL) cardiac amyloidosis (AL-CA), the wild-type transthyretin (ATTRwt-CA), and mutant-type transthyretin (ATTRmt-CA) are the most studied types of SA. The literature describes only single cases of two types of SA in the same patient. OBJECTIVE: To identify and determine the clinical and morphological characteristics of combined types of SA in patients with biventricular chronic heart failure (CHF). MATERIAL AND METHODS: Eighty autopsy protocols for biventricular CHF deaths were retrospectively analyzed. Immunohistochemistry and confocal laser scanning microscopy (CLCM) with antibodies to amyloid A (AA), serum amyloid-P (SAP), prealbumin, and immunoglobulin kappa (κ) and lambda (λ) light chains were performed. RESULTS: The myocardium showed a combination of different types of SA in 6 (7.5%) cases, including Alλ-CA+ATTR-CA, ALκ-CA+ATTR-CA, and AA-CA+ATTR-CA in 4, 1, and 1 cases, respectively. Macroscopically, the heart mass averaged 470±20 g; the thickness of the left and right ventricular myocardium was 1.5±0.2 and 0.4±0.1 cm, respectively; the interventricular septum averaged 1.2±0.2 cm; and the cardiac index was 0.008. The myocardium was dense, dark red with diffuse layers of whitish dense fibrous connective tissue; the heart cavities were enlarged. Microscopically, in 25% of cases, all heart parts had ALλ-CA that was characterized by massive amyloid deposits localized predominantly in the intramyocardial vessel wall, intermuscular connective tissue, and perivascularly. The myocardium also displayed small amyloid deposits of ALλ-CA and ATTR-CA in the intermuscular connective tissue and intramyocardial vessel wall. Amyloid deposits were located in different parts of the myocardium; there were also areas of co-localization of ALλ-CA+ATTR-CA. CONCLUSION: The combined types of SA occurred under the guise of coronary heart disease and the dilated cardiomyopathy phenotype. The combined amyloid AL-CA and ATTR-CA was generally localized in the interstitium and myocardial vessels. There were also small areas of co-localization of amyloid deposits, which were found mainly in the intramyocardial vessels.

Cause of death based on systematic post-mortem studies in patients with positive SARS-CoV-2 tissue PCR during the COVID-19 pandemic.

IMPORTANCE: Assessment of the causative association between the COVID-19 and cause of death has been hampered by limited availability of systematically performed autopsies. We aimed to present autopsy-confirmed causes of death in patients who died with COVID-19 and to assess the association between thrombosis and diffuse alveolar damage consistent with COVID-19 (DAD). METHODS: Consecutive forensic (n = 60) and clinical (n = 42) autopsies with positive post-mortem SARS-CoV-2 PCR in lungs (age 73 ± 14 years, 50% men) were included. The cause of death analysis was based on a review of medical records and histological reports. Thrombotic phenomena in lungs were defined as pulmonary thromboembolism (PE), thrombosis in pulmonary artery branches or microangiopathy in capillary vessels. RESULTS: COVID-19 caused or contributed to death in 71% of clinical and 83% of forensic autopsies, in whom significant DAD was observed. Of the patients with COVID-19 as the primary cause of death, only 19% had no thrombotic phenomena in the lungs, as opposed to 38% amongst those with COVID-19 as a contributing cause of death and 54% amongst patients whose death was not related to COVID-19 (p = 0.002). PE was observed in 5 patients. Two patients fulfilled the criteria for lymphocyte myocarditis. CONCLUSIONS: Vast majority of all PCR-positive fatalities, including out-of-hospital deaths, during the SARS-CoV-2 pandemic were related to DAD caused by COVID-19. Pulmonary artery thrombosis and microangiopathy in pulmonary tissue were common and associated with the presence of DAD, whilst venous PE was rarely observed. Histology-confirmed lymphocyte myocarditis was a rare finding.

[Sepsis: from systemic inflammatory response syndrome to organ dysfunction]. / Sepsis: ot sindroma sistemnoi vospalitel'noi reaktsii do organnoi disfunktsii.

Based on their extensive experience and literature data, the author outlines difficulties in the morphological diagnosis of sepsis, by taking into account the current clinical classification. Occurring not only in sepsis and lacking clear morphological criteria, a systemic inflammatory response and organ dysfunction cannot be absolute signs of sepsis diagnosis. The author gives the morphological characteristics of the systemic inflammatory response, septic shock, and organ dysfunction.

[Anatomical pathology of novel coronavirus (COVID-19) infection. First impressions]. / Patologicheskaya anatomiya novoi koronavirusnoi infektsii COVID-19. Pervye vpechatleniya.

To date, descriptive results of a clinical and morphological study of novel coronavirus COVID-19 infection, mainly of the lungs, have appeared. However, in other organs, primarily in the cardiovascular system, there are substantial structural changes that lead to multiple organ dysfunction and contribute to death. OBJECTIVE: To analyze the thanatogenetic significance of novel coronavirus COVID-19 infection in different age and gender groups and to describe the main morphopathological manifestations in various organs. MATERIAL AND METHODS: The investigators carried out a comprehensive analysis of 700 autopsies of people disease from the novel coronavirus COVID-19 infection, which included an examination of gross changes reflected in the autopsy protocols and forensic medical examination reports, as well as that of microscopic changes detected during histological examination of organs. Immunohistochemistry (IHC) using mouse or rabbit antibodies to CD34, CD68, EMA, Ki67, caspase-3, and VEGF was employed in some observations. RESULTS: The novel coronavirus COVID-19 infection was the primary cause of death. Acute respiratory and pulmonary heart failure and multiple organ dysfunction became the leading thanatogenetic mechanisms in COVID-19. Cardiovascular disease, diabetes mellitus, and obesity were the most common diseases in patients with COVID-19. The most pronounced lung changes in COVID-19 were determined with a predominance of multiple total bilateral lesions of the lower lobes of the lungs, which was manifested by virus-induced changes in the parenchyma and stroma, as well as by microcirculation disorders. Acute dyscirculatory and ischemic changes in the parenchymal organs dominated in tissue damage caused by the virus. CONCLUSION: The changes in different organs of those who have died from the new coronavirus COVID-19 infection are stereotyped and include the manifestations of virus-induced action and a systemic inflammatory response with mainly microvasculature alteration, which leads to the development of coagulopathies and, accordingly, to total hypoxia.

Intravital and postmortem diagnostics of myocardial hypertrophy of the left ventricle:identity or convention?

AIM: The aim of the study is to assess the compliance of the results of electrocardiographic (ECG) and echocardiographic diagnostic methods of hypertrophy of left ventricular myocardium (LVH) with the postmortem finding of measurement of left ventricular myocardium mass (LVM). MATERIALS AND METHODS: We examined the data of intravital study of anthropometric measurements [age, height, weight, body mass index (BMI)], instrumental results [12-lead ECG, EchoCG], as well as the postmortem finding (direct measurement of LVM at autopsy) in 15 patients of general therapy department. While analyzing ECG we studied as conventional ECG criteria for the detection of LVH as well as the author's own criteria based on two models (regression and discriminant analyses), including voltage, sex and age criteria. Echocardiographic diagnostic method used to calculate LVM (according to ASE formula) and left ventricular mass index (LVMI). Postmortem finding of LVM was carried out according to the standard measurement method. According to the absence of the single conventional postmortem finding of measurement of LVH, we considered three different variants of the postmortem finding of LVH: the criterion of K. Bove et al. (CB); the criterion of A.M. Lifshitz, also called ventricular index (VI) and the criterion of P. Casale - the left ventricular mass index at autopsy (LVMI). RESULTS: Conventional ECG criteria for the detection of LVH showed high specificity (71-100%) using any method of the postmortem finding of measurement, but were characterized by extremely low sensitivity (0-37.5%). Their overall diagnostic accuracy was higher on using K. Bove or A.M. Lifshitz criteria (40-66.7%) and low - on using the criterion of P. Casale (13.3-40%). The author's ECG criteria were less specificity (50-100%) and had higher sensitivity (54-75%), and their diagnostic accuracy remained higher and showed small dependence on the method of the postmortem finding of measurement of LVH (60-66.7%). CONCLUSION: Usually the ECG criteria to diagnose left ventricular hypertrophy were expectedly showed low sensitivity using any method of the postmortem finding of measurement. Meanwhile, the author's own ECG criteria associated with the most sensitive electrocardiographic characteristics to LVH and sex and age-specific indexes of the examined patients exceeded the conventional ECG criteria in sensitivity and diagnostic accuracy.

[Molecular biological markers for proliferation, apoptosis, and angiogenesis in diffuse toxic goiter]. / Molekuliarno-biologicheskie markery proliferatsii, apoptoza i angiogeneza pri diffuznom toksicheskom zobe.

The pathogenesis of diffuse toxic goiter has not yet been fully understood. The literature increasing commonly focusses on the issues related to the processes occurring in the thyroid gland itself: proliferation, apoptosis, and angiogenesis. AIM: to investigate clinical and laboratory parameters, as well as the expression of Ki-67, Bcl-2, Bax, Fas-L, CD34, VEGF, and FGF proteins in various postoperative outcomes of patients operated on for diffuse toxic goiter. SUBJECTS AND METHODS: The investigation enrolled 24 women who had undergone surgery using the technique described by E.S. Drachinskaya. Immunohistochemical tests were carried out according to the standard protocol. The expression of Ki-67, Bcl-2, Bax, Fas-L, CD 34, VEGF, angiopoietin, and FGF proteins was determined. RESULTS: The patients with postoperative thyrotoxicosis were ascertained to have a significantly greater expression of anti-apoptotic protein Bcl-2, proliferation marker Ki-67, vascular factors (FGF, VEGF), and CD 34. CONCLUSION: The relative expression area of the anti-apoptotic protein Bcl-2 of more than 2.19 or the proliferation protein Ki-67 of more than 1.059 was found to predict the development of postoperative thyrotoxicosis with an accuracy of higher than 85%.

[Pulmonary histiocytosis from Langerhans cells as the problem of clinical morphology].

There are discussed modern views on one of the most difficult diagnosed forms of pulmonary dissemination. They relate to the dynamics of granulomatous changes in the lung tissue at the cellular and subcellular level as well as a characteristic of the immunophenotype of Langerhans cells. At present the frequency of this disease increases, which improves the responsibility for the timely diagnosis based on performing explicit clinical and morphological studies.

[The informative value of oral mucosal biopsy for the diagnosis of systemic amyloidosis].

One hundred and thirteen oral mucosal biopsy specimens were analyzed in patients suspected of having systemic amyloidosis. Histological, immunohistochemical, and genetic studies and polarized light microscopy revealed oral amyloid deposits in 72.6% of cases, including 63.5% with metabolic syndrome and 36.5% with another etiology of chronic heart failure (coronary heart disease, cardiomyopathy). Systemic amyloidosis was found in 13.4% of cases (hereditary transthyretin, AL, and senile forms in 1.8, 10.5, and 1.1% cases, respectively). An anterior abdominal wall skin flap was a valid location to reveal the systemic forms of amyloidosis. Patients with metabolic syndrome and periodontal diseases may have local oral amyloidosis.

[Oral status and oral mucosa blood circulation changes in patients with chronic heart failure].

The objective of this study was to characterize dental status and oral mucosa blood flow in patients with chronic heart failure and amyloid deposits in oral mucosa. Histological and immunohistochemical analysis of 80 oral mucosa biopsies taken from patients aged 32-72 years with chronic heart failure I-IV NYHA functional class was carried out. It detected a systemic amyloidosis in 15.7% of cases; a local amyloid deposition in oral mucosa was found in 58.5% of cases. Amyloid deposition in oral mucosa was associated with severe chronic generalized periodontitis in more than a half of cases. Amyloid deposits in oral mucosa were revealed more often in patients with metabolic syndrome (63.5%). The article describes dental status and oral mucosa blood flow in patients with heart failure.

[Hypertrophic cardiomyopathy. Clinical and morphological comparisons].

The paper comparatively analyzes myocardial morphology in children and adults with hypertrophic cardiomyopathy. All the cases analyzed had its obstructive form and significant asymmetric left ventricular hypertrophy--hypertrophy of the ventricular septum (VS). When stratifying the risk of sudden death from the obstructive form of the disease in adults, the most important characteristics are shown to be less than 45 years of age, stromal enlargement in the right VS closer to the endocardium of the right ventricle; and in some cases this fact must be considered when choosing a management tactic.

[Desmin-related cardiomyopathy].

The observation of 26 years old patient with desminopathy declared itself by hypertrophied cardiomyopathy with its transformation into restrictive phenotype is presented. The features of pathologic course at the patient were a dominance and diversity of cardiac manifestations. Endomyocardiac biopsy allowed suspecting the desminopathy confirmed by genetic analysis. Morphological features of desmin-related cardiomyopathy were irregular desmin conglomerates mainly located under sarcolemma and an indirect histological signs of idiopathic cardiomyopathy as well nuclear polymorphism, perinuclear "nimbus", chaotic located myofibrils.

[Evaluating the activity of the apoptosis-regulating genes from Bcl-2, Bax expression, and caspase-3 activity in bronchial epithelial cells in patients with asthma].

The specific features of bronchial epithelial cell apoptosis in asthma were studied, by evaluating the activity of the apoptosis-regulating genes Bcl-2, Bax, and caspase-3. Fibrobronchoscopy with target biopsy of the bronchial mucosa was carried out in 21 asthmatic patients (the latter had given informed consent). The expression of Bcl-2, Bax, and CPP32 (caspase-3 activity) was determined in the bronchial epithelial cells by the immunohistochemical technique using the DAKO kits. Allergic asthma is characterized by higher Bcl-2 and lower Bax expression than non-allergic asthma and in patients receiving systemic glucocorticosteroids. The similar nature of changes was found in the analysis of the Bcl2/Bax ratio. Regardless of the type of asthma, the expression of caspase-3 was rather high. The specific features of impaired bronchial epithelial cell apoptosis in different types of asthma can determine the pathogenetic value of apoptotic disorders in the persistence of allergic inflammation.

[Cardiac manifestations of amyloidosis].

Amyloidosis is shown by a group of diseases with a variability of clinical and morphological manifestations determining difficulties in its diagnosis. The cardiovascular system is commonly the site of involvement in different forms of amyloidosis. The variants of cardiac involvement in the pathological process in amyloidosis are outlined depending on various precursor proteins. The specific features of different forms of cardiopathic amyloidosis are described in relation to its type.

[Myocardial and renal morphological changes in drug addicts with infective endocarditis].

The autopsy specimens of the myocardium and kidneys from 233 patients with infective endocarditis (142 and 91 with and without a history of drug abuse, respectively) were studied by conventional microscopy and immunohistochemistry. In the drug abusers (DA), myocytolysis was a dominant form of myocardial damage and in the non-DA that was contraction degeneration. In DA, lower cardiomyocytic cl-2 expression arouses speculations on the possible role of apoptosis in the pathogenesis of heart failure in this group of patients. Membranous glomerulopathy was a hallmark of renal pathology in DA, contrasting with the predominance of mesangial lesions in non-DA. Increased CIC deposition may be regarded as a major contributing factor.

[The role of a signal lymph node in surgical treatment of gastric cancer].

A method of intraoperative mapping of the lymph outflow tracts was used in 32 patients for a detection of the signal lymph node in gastric cancer using a lymphotropic stain BLUE PATENT V. The test-sensitivity was 78%. The intraoperative mapping of the lymph outflow tracts allows the volume and zone dissection in operations for gastric cancer to be exactly determined. The detection of the "signal" lymph node and its immunohistochemical investigation increases the accuracy of postoperative staging of gastric cancer. The absence of metastases in the signal lymph node in gastric cancer is not a determining criterion for refusal to perform lymphodissection in D2 volume.

[The Saint Petersburg Society of Pathologists is 100 years old].

The paper describes the history of the Saint Petersburg Society of pathologists since it was founded in 1909. It shows what great role is played by outstanding Russian medical scientists who have established their own schools of pathomorphologists and are respected in our and foreign countries. The activities of the society's members in research developments in cardiovascular and infectious diseases, cancer morphology, etc., as well as their practical participation in the work of the health care facilities of the city and its region are characterized. This work is characterized by the permanent conformance to the world standards of human pathology as a basic science of the present day, by steadily maintaining the established traditions of the Saint Petersburg school. The authors follow the evolution of a pathologist and his/her becoming to a clinical pathologist as the problems facing pathomorphology are extended and its methodic and methodological capacities are improved.

[Immunomorphological characteristics of pulmonary langerhans cell histiocytosis].

Lung tissue specimens, obtained during lung biopsy or resection, were morphologically and immunohistochemically studied in 27 patients with Langerhans cell (LC) histiocytosis (LCH). The latter was diagnosed on the basis of the expression of CD1a and S-100. Without immunophenotyping, its diagnosis was difficult due to impaired tissue architectonics (sclerosis, bullous transformation) and artifacts that were inevitably present during lung biopsy. LCs in the infiltrates were shown to be capable for apoptosis. Induction of LC apoptosis may be regarded as a therapeutic strategy.

[Cellular aspects of hypertrophic cardiomyopathy pathogenesis: the role of cardiomyocyte polyploidy and activation of the proliferating cell nuclear antigen in the myocardium].

Mechanisms of hypertrophy development in hypertrophic obstructive cardiomyopathy (HOCM) have not been enough investigated. In our study, there have been examined patients with severe HOCM at different ages, including children, and patients with essential arterial hypertension (EAH). There was found, that HOCM in children compared to adults was characterized by considerable interventricular septum (IVS) hypertrophy and it was accompanied by the acceleration of cardiomyocyte polyploidy. The average ploidy level of cardiomyocytes in children with HOCM was higher than analogous indices in adults. The average ploidy level of nuclei, the part of PCNA-positive nuclei and polyploidic nuclei of cardiomyocytes in aduls with HOCM were authentically higher than in patients with EAH. Activation of the nuclear antigen in stromal cells was detected only in patients with HOCM. Our findings provide evidence of an important role of cardiomyocyte polyploidy and activation of the proliferating cell nuclear antigen in development of the myocardial hypertrophy in patients with HOCM.