Von Hippel-Lindau (VHL) disease is a rare autosomal dominant genetic disease characterized by the formation of benign and malignant tumors. From 10 to 20% of patients develop a pancreatic neuroendocrine tumor (panNET). This article presents a clinical and morphological case that describes a well-differentiated neuroendocrine tumor of the pancreatic head accompanied by VHL syndrome. Positive Synaptophysin and Chromagranin A staining of tumor cells confirmed the diagnosis. The proliferation index (Ki-67) was less than 3%. In addition, serous cystadenoma without signs of neuroendocrine differentiation was found in the pancreatic tail, which was confirmed by positive reaction with antibodies to CA IX and MUC6 and a negative reaction with antibodies to Synapthophysin in the epithelial cells. Keywords: von Hippel-Lindau syndrome, neuroendocrine tumor, pancreas, immunohistochemical study

Toxic environmental pollutants pose a health risk for both humans and animals. Accumulation of industrial contaminants in freshwater fish may become a significant threat to biodiversity. Comprehensive monitoring of the impact of environmental stressors on fish functional systems is important and use of non-invasive tools that can detect the presence of these toxicants in vivo is desirable. The blood circulatory system, by virtue of its sensitivity to the external stimuli, could be an informative indicator of chemical exposure. In this study, microscopic photoplethysmography-based approach was used to investigate the cardiac activity in broad whitefish larvae (Coregonus nasus) under acute exposure to cadmium and phenol. We identified contamination-induced abnormalities in the rhythms of the ventricle and atrium. Our results allow introducing additional endpoints to evaluate the cardiac dysfunction in fish larvae and contribute to the non-invasive evaluation of the toxic effects of industrial pollutants on bioaccumulation and aquatic life.

Noninvasive, rapid, and robust diagnostic techniques for clinical screening of tumors located in arbitrary areas of the human body are in demand. To address this challenge, we analyzed the feasibility of photoplethysmography-based angiography for assessing vascular structures within malignant and benign tumors. The proposed hardware and software were approved in a clinical study involving 30 patients with tumors located in the legs, torso, arms, and head. High-contrast and detailed vessel maps within both benign and malignant tumors were obtained. We demonstrated that capillary maps are consistent and can be interpreted using well-established dermoscopic criteria for vascular morphology. Vessel mapping provides valuable details, which may not be available in dermoscopic images and can aid in determining whether a tumor is benign or malignant. We believe that the proposed approach may become a valuable tool in the preliminary cancer diagnosis and is suitable for large-scale screening.

Against the background of a steady increase in the number of oncological diseases, as well as the complexity of the primary morphological diagnosis of malignant neoplasms (MNT) and precancerous conditions, especially in the regions of the Russian Federation, in 2019, the creation of a number of Reference Centers (RCs) for immunohistochemical, pathomorphological, molecular genetic methods was initiated research within the framework of the federal project “Fight against oncological diseases”. In 2020, on the basis of the centralized pathoanatomical department of the Clinical Center of Sechenov University, the RC began its work. Aim. To analyze the work of the RC of Sechenov University and compare the results obtained with the tasks of the federal project.Materials and methods. The data of histological, immunohistochemical studies from the registers of receipt of biopsy (surgical) materials and the issuance of the results of intravital pathoanatomical studies (account forms 014-2 / y and 057-y / 04), as well as data from the Telemedicine system of remote consultations, were analyzed. Results. For 21 months of work, the RC consulted 1476 requests received from 70 constituent entities of the Russian Federation. More than 10 % of reference diagnoses were made in a remote format through the Telemedicine system of remote consultations at the federal and regional levels using digital pathology techniques.Conclusion. Despite the obvious need for the work of RCs, there are still a number of issues that have a signifcant impact on the quality of diagnostic processes: specialization of specifc RCs, expansion of the range of incoming clinical and morphological diagnoses. It also requires attention to regularly improve the skills of RC employees in Russian and international educational systems and to equip the RC, frst of all, with virtual resources. The experience of the RC has demonstrated the importance of a second medical expert opinion in the primary diagnosis and verifcation of the diagnosis of malignant neoplasms of various localizations for the regions of the Russian Federation, where the acute problem is the general shortage of general pathologists and expert doctors.

Today, ART cycles using a donor egg cell are used more often, but this group of pregnancies has not been sufficiently studied in terms of detecting structural predictors of pregnancy complications caused by a special immunological relationship between the recipient mother and allogeneic blastocytes. A comprehensive clinical and morphological study of 89 allogeneic pregnancies was carried out. The morphological study was performed on placental sites biopsies taken at caesarean section (H & E, Orcein), for immunohistochemical analysis PanCK (AE1 / AE3), SMA (1A4), CD56 (123C3.D5), CD138 (B-A38), CD4 (SP35), CD25 (SP176), CD8 (SP16) were used as primary antibodies. A defect of the remodeling of the spiral arteries, including in subgroups without preeclampsia, the formation of perivascular foci of chronic inflammation were found (the accumulation of CD8 + T lymphocytes, CD56 + NK cells, CD138 + plasma cells, HLA-DR + dendritic cells). In subgroups with PE, significant changes were found for T lymphocytes (51.04 ± 2.3, 55.36 ± 11, 7 versus 37.12 ± 2.3), plasma cells (19.5 ± 3.2, 21.43 ± 8.4 versus 8.94 ± 1.2), Kruskal-Wallace test. Structural and immunohistochemical features of the allogenic placental bed may reflect the complexity of cytotrophoblast invasion and induction of maternal immunity with the formation of immune inflammation.

Aim: to present a clinical and morphological observation of an extremely rare combination of medullary carcinoma of the jejunum and intestinal lymphangiectasia in a 33-year-old patient with clinical features of malabsorption syndrome over the 10 years.Key points. An autopsy revealed a tumor formation spreading from the wall of the jejunum to the mesentery, with metastases to the mesenteric lymph nodes. The medullary carcinoma with positive expression of СD117, DOG1, EMA, PanCK, PDL-1, vimentin, mosaic non-intense expression of CA19-9, calretinin, CD10, CDX2, CEA, MUC-5AC, SATB2, and negative reaction to ALK, CD3, CD8, CD20, CD30, CD31, CD34, CD45, CD56, chromogranin, CK7, CK20, desmin. The proliferative index was high: Ki-67 > 80 %. Moreover, during the histological examination of the intestinal wall, intestinal lymphangiectasia complicated by the malabsorption syndrome was revealed.Conclusion. The uniqueness of this clinical and morphological case is in the combination of medullary carcinoma of the jejunum metastasized to the mesenteric lymph nodes with the underlying intestinal lymphangiectasia accompanied by the development of malabsorption syndrome.

Objective: to present up-to-date scientific information concerning the role of astrocytes in neuroinflammation. A total of 63 publications were analyzed, obtained from Cochrane Library and PubMed using the following search queries: "astrocytes and neuroinflammation", "reactive astrocytes", "neuroglia and neuroinflammation". 45 publications were selected for the review. The analyzed literature was published in the year range of 2000 to 2020. It comes to a conclusion that the role of astrocytes in neuroinflammation is controversial. The cells have both protective and destructive effects. It is important to understand that the activity of reactive astrocytes depends on their topographic location and microenvironment, as well as mediators that are secreted by CNS resident and non-resident cells. Understanding the role of astrocytes in neuroinflammation and their regulatory mechanisms is necessary for the implementation of their therapeutic potential.

Introducing the concept of digital twins in healthcare, medical education, and research is a complex multistage challenge requiring participation of multidisciplinary teams. In pursuing this goal, we have created a validated database of scans of colorectal tumor slides associated with relevant clinical and histological information. This database is also linked to the blood bank, which opens a wide range of opportunities for further research. Herein, we present our experience within the scope of the digital twins initiative.

One of the most serious pregnancy complications is currently considered as a violation of cytotrophoblast invasion, particularly, a pathologically increased depth of invasion, leading to the formation of the placental increment (placenta accreta), ingrowth (placenta increta), and germination (placenta percreta). Cytotrophoblast invasion is regulated through subtle intercellular interactions, an important role among which is played by integrins, transmembrane glycoproteins that contribute to the immersion of cytotrophoblast in the endometrium and myometrium. The balance disturbance in the expression of 11, 51, and 64 integrins after normal implantation form a pathological extravillous trophoblast (EVT) phenotype by the blastocyst. This review examines the importance of integrins, collagens, and fibronectin in the formation of placental ingrowth (placenta accreta spectrum).

BACKGROUND:There are few reports of trigger wrist in the literature, as it is a rare pathology. Furthermore, various authors report that it is also hard to diagnose. It manifests with neurological symptoms at the affected wrist, which are usually induced by wrist movement, and can lead to partial or full loss of wrist function and sensitivity. The reason for reporting this specific case is that it was hard to differentiate between trigger finger and trigger wrist by clinical symptoms; no pathology was palpable or clearly seen on magnetic resonance imaging scan of the wrist. We propose a new diagnostic statement relative to this pathology.CASE PRESENTATION:A case of a 45-year-old white slavic man with trigger wrist associated with carpal tunnel syndrome, caused by a fibroma of the flexor tendon sheath, is reported. Despite careful clinical examination, it was not possible to differentiate between trigger finger and trigger wrist. Magnetic resonance imaging was performed to arrive at the right diagnosis but did not reveal any pathology in the wrist area. Carpal tunnel release was performed with a fibroma identified and excised. Wrist function was maintained well; no signs of carpal tunnel syndrome were seen at last follow-up.CONCLUSIONS:Trigger wrist can be misdiagnosed as trigger finger even if adequate clinical evaluation is performed, and this can lead to inadequate treatment. We state that, when clinical symptoms of both trigger wrist and trigger finger are present, except painful palpation of the A-1 pulley region, the case should be referred to as trigger wrist.

According to the World Health Organization, there are about 5.9 million annual perinatal deaths worldwide, the etiology of which, on average, remains unspecified in 15–50% of cases. This review presents an analysis of the existing classification systems for causes of perinatal mortality, estimates the current data on risk factors and possible pathophysiological mechanisms of sudden fetal and infant death, identifies several world health problems that prevent the reduction of stillbirth and neonatal mortality rates, and suggests the ways of their solution. Key words: perinatal mortality, stillbirth, sudden intrauterine death syndrome, brainstem, cardiac conduction system

The aim of the study was to reveal the effect of neurostimulation with the TKPRPGP neuropeptide on the expression intensity of Doublecortin and Nestin in the olfactory bulb of white Wistar rats using immunohistochemical and computer analysis methods. An isolated assessment of early progenitor differentiation by the density of nestin-positive structures showed that stimulation from birth to 14 days preserves the level of nestin expression, preventing its decrease. When the administration of the neuropeptide is stopped, the expression of nestin decreases sharply, starting from the central zones of the bulb, and after three weeks it is no longer present. The dynamics of doublecortin positive structure density reflects an increase upon neuropeptide administration. Each course of neuropeptide administration caused an increase in the density of the marker, but the degree of effectiveness decreased with age, and the duration of the effect decreased. In conclusion, administration of the neuropeptide TKPRPGP to rats at an early age prolongs the expression of nestin and doublecortin in the olfactory bulbs of rats up to 35 days and up to 74 days of observation, respectively. The administration of the neuropeptide in adulthood does not lead to re-expression of these markers.

A clinical case of management of a pregnant woman (surrogacy) with dichorionic triamniotic triplets, self-reduction of one fetus from triplets in the gestation period of 13 weeks, intrauterine death of the second fetus at week 20 of pregnancy and delivery of the third live fetus in full-term pregnancy. Key words: surrogacy, triplets, multiple pregnancy, intrauterine fetal death, immunological tolerance

Objective:To study the structural and immunohistochemical features of placentas in women after assisted reproductive technology (ART) with allogeneic eggs (oocyte donation and surrogate motherhood).Study Design:The study involved 89 women whose pregnancy occurred as a result of in vitro fertilization (IVF) with a donor egg in a surrogate motherhood program (IVF-SM,n= 47 patients) or oocyte donation (IVF-DO,n= 42). The comparison group consisted of 21 patients in whom pregnancy occurred as a result of IVF with their own egg (IVF-OE). A clinical and anamnestic analysis of the pregnant women was carried out. Morphological and immunohistochemical studies were performed on placental material. Immunohistochemical analysis of CD8, CD56, CD138, and CD25/CD4 markers indicating the processes of impaired tolerance in placenta was carried out. -Results:We observed a predominance of women aged >40 (range 42.7-3.91) years with a burdened somatic and obstetric-gynecological history and a high incidence of hypertensive pregnancy complications, such as gestational arterial hypertension (27.4%) and preeclampsia (28.5%), in the IVF-DO group. The IVF-SM group included mainly somatically healthy women aged <30 (29.4-3.19) years with a high risk of termination of pregnancy in the third trimester (49.6%) and premature birth (21.6%). Placentas taken from women after allogeneic pregnancy had pronounced signs of immune alteration, such as chronic histiocytic intervillositis, lymphoplasmacytic deciduitis, chronic chorioamnionitis, chronic villitis, and perivillous fibrinoid with lymphocytes (p[F] < 0.05). Immunohistochemical study of the placentas showed accumulation of CD138+ plasma cells, CD8+ T lymphocytes, and uterine natural killer cells, and a decrease in the number of CD25/CD4+ regulatory T cells (Tregs) in the structures of the uteroplacental region (Kruskal-Wallis test,p< 0.05).Conclusion:Placentas after IVF with oocyte donation and surrogate motherhood programs are characterized by similar changes, associated with the development of chronic inflammation in the structures of the placenta and immunohistochemical signs of impaired immunological tolerance at the maternal-fetal interface. The data we obtained allow us to classify pregnancies under surrogate motherhood programs as a risk factor for the development of pregnancy complications with immune pathogenesis.

On March 11, 2020, the World Health Organization declared COVID-19 apandemic. Despite a large number of scientific publications concerning the clinical picture and trea tment methods, data on structural changes of internal organs in COVID-19 is still insufficient. This review presents and analyzes several clinical cases published by research groups in various countries. COVID-19 infection is caused by a SARS-CoV-2 virus that binds to the angiotensin-converting enzyme 2 ACE2 receptor. Interaction with this receptor is the initial stage of pathogenesis. The morphological picture is similar to pneumonia caused by SARS-CoV and MERS-CoV: at the initial stage, a picture of shock lungs develops, later it ends in fibrosis and organizing pneumonia. One of the most severe complications is acute respiratory distress syndrome, which is observed in some clinical cases reviewed. In this article, we collected cases of clinical and morphological studies of patients with COVID-19, published in international peer-reviewed medical literature to date.

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.