[Metachronous tumors of the stomach in a patient with autoimmune gastritis]. / Metakhronnye opukholi zheludka u patsientki s autoimmunnym gastritom.

Stomach cancer continues to be a global health problem, ranking 5th among cancers and 4th among the causes of death from cancer in the world. Autoimmune atrophic gastritis is a chronic autoimmune disease characterized by the production of antibodies to parietal cells and intrinsic factor, followed by atrophy of the mucous membrane of the body and fundus of the stomach. Chronic autoimmune inflammation can lead to damage to the genetic apparatus of the cell and trigger a multi-stage process of carcinogenesis. Our article presents an unusual case of three different gastric tumors, including adenocarcinoma with microsatellite instability, in a patient with autoimmune gastritis.

[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.

[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.

[Adrenocortical cancer: morphological variants, immunohistochemical characteristics]. / Adrenokortikal'nyi rak: morfologicheskie varianty, immunogistokhimicheskaya kharakteristika.

Adrenocortical cancer (ACC) is a rare endocrine malignancy of the adrenal cortex, which has an unfavorable prognosis and extremely aggressive clinical behavior in most cases. Nevertheless, cases of a more favorable disease course with late metastasis and slow progression have been described. In 2017, the International Agency for Research on Cancer (IARC) and the World Health Organization (WHO) in the 4th edition of the Classification of Tumors of the Endocrine Organs identified histological variants of ACC, such as classical, oncocytic, myxoid, and sarcomatoid ones, indicating the morphological heterogeneity of this tumor. OBJECTIVE: To provide a detailed description of the morphological variants of ACC with an emphasis on their histological characteristics and the expression of immunohistochemical markers. MATERIALS AND METHODS: A total of 75 cases of ACC were analyzed in the adult population diagnosed as having the morphological variants in accordance with the International Histological Classification of Adrenal Tumors (WHO, 2017). Monoclonal antibodies to SF1, Inhibin A, Melan A, Ki-67, p53, and antimitochondrial antibodies were used for immunohistochemical diagnosis. RESULTS: The classic, oncocytic, and myxoid subtypes of ACC were found in 51 (68%), 15 (20%), and 9 (12%) cases, respectively. The functional activity of the tumors was observed in 43% (n=18) in the classic variant of ACC; moreover, the clinical picture was manifested by the symptoms of hypercorticism (38%) and virilization (5%). There were no significant differences in hormonal activity between different morphological variants. The characteristics of the above histological variants of the tumor was determined with a description of growth patterns that can improve the diagnosis of ACC. The diagnosis of ACC can be confirmed by an immunohistochemical study; the required minimum panel of markers should include SF1, Melan A, and Inhibin A. The Ki-67 proliferative activity index showed significant differences (p=0.0056) when it was determined in the morphological variants of ACC. CONCLUSION: Despite the determination of a minimal immunohistochemical panel to confirm the diagnosis of ACC, it is important to remember that each histological variant may be characterized by the different expression of immunohistochemical markers. The identification of morphological variants of ACC and the use of specific, sensitive, and prognostically significant immunohistochemical markers will allow clinicians and pathologists to more accurately judge the biological properties of this tumor and the clinical course of the disease.

[Molecular genetic markers and criteria for the prediction of adrenocortical carcinoma]. / Molekuliarno-geneticheskie markery i kriterii prognoza adrenokortikal'nogo raka.

Studies of the last decade have demonstrated that the morphological and immunophenotypic patterns of adrenocortical carcinoma (ACC) have a high heterogeneity in both the occurrence of various tumors and the development of a solitary tumor. Carcinogenesis of ACC, like most neoplastic processes, is associated with mutations in at least 15 driver genes, with a wide range of chromosomal aberrations, epigenomic changes, and alterations of the microRNA profile. According to the literature, isolated genetic damage is also insufficient for the manifestation of the malignant phenotype of adrenocortical cells. Knudson's two-hit hypothesis is implemented in at least germline mutations: the development of ACC requires a second genetic event occurring in somatic cells, which leads to inactivation of the second allele of the gene. ACC is an extremely heterogeneous disease, which determines the complexity of differential diagnosis with benign adrenocortical tumors and that of prediction of the clinical course. Another no less important issue is the lack of valid predictors for the efficacy of mitotane, the use of which may be associated with severe adverse effects.

[Current criteria for the diagnosis of adrenocortical carcinoma]. / Sovremennye kriterii diagnostiki adrenokortikal'nogo raka.

Adrenocortical carcinoma is a rare malignant tumor of the adrenal cortex with an unfavorable prognosis. In 2017, the International Agency for Research on Cancer (IARC) and the World Health Organization (WHO) published the 4th edition of the WHO Classification of Tumors of Endocrine Organs. The updated classification reflects a multidisciplinary experience in diagnosing and predicting the course of adrenal cortex tumors, obtained on the basis of current studies. This paper highlights the key provisions of the updated WHO classification for adrenocortical carcinoma.

[Diagnostic problems of histological remission in patients with inflammatory bowel disease]. / Problemy diagnostiki gistologicheskoi remissii u bol'nykh s vospalitel'nymi zabolevaniiami kishechnika.

AIM: to analyze the generally accepted histological criteria for diagnosing the activity of inflammatory bowel disease (IBD) in patients with therapy-induced endoscopic remission. SUBJECTS AND METHODS: Colon biopsy specimens from 57 patients aged from 19 to 52 years (mean age 31±2.5 years), including 41 patients with ulcerative colitis (UC) and 16 with Crohn's disease (CD) affecting the colon, were examined. All the patients had no clinical signs of disease activity; endoscopic examination diagnosed remission (none or minimal changes). The biopsy specimens were taken from all colon segments during colonoscopy and processed by conventional methods. RESULTS: Persistence in chronic inflammation with signs of its activity (neutrophils in an infiltrate and cryptitis) and mucosal structural changes (no histological remission) were found in 29.3% of the patients with UC and 37.5% of those with CD (only in 31.6% of the patients). Persistence in chronic inflammation without signs of its activity and/or mucosal structural changes (incomplete histological remission) were detected in 80.5, 81.25, and 80.7% of the patients, respectively. Complete histological remission without mucosal inflammatory and structural changes was observed only in 19.5, 18.75, and 19.3% of the patients, respectively. CONCLUSION: The investigation shows that histological remission is still difficult to achieve to date, despite the use of the present-day treatment protocols for IBD. On the other hand, the conventional morphological criteria for the diagnosis of histological remission in IBD are quite subjective and need further discussion and agreement. Whether there may be a complete structural and functional recovery of the colon mucosa remains open.

[Somatostatin receptor expression in the ileal mucosa of patients with inflammatory bowel disease].

AIM: to investigate the specific features of somatostatin receptor expression in the ileal mucosa of patients with inflammatory bowel disease (IBD). MATERIAL AND METHODS: Ileal biopsy specimens from 42 patients aged 22 to 55 years, including 16 patients with Crohn's disease (CD), 14 with indeterminate colitis of IBD unclassified (IBDU), and 12 with the unchanged ileal mucosa (a comparison group). Immunohistochemical examination was performed using anti-somatostatin receptor type 2 (SSTR-2) antibodies (Epitomics, USA). SSTR2-positively stained cells were counted per 100 epitheliocytes. RESULTS: There were three receptor expression types: predominantly membranous, cytoplasmic, and mixed (membranous-cytoplasmic). Calculation of cells with membranous expression indicated that the median was 1 in the patients with Crohn's disease (interquartile range (IQR) 0.5), 3 in those with IBDU (IQR 2.5), and 2 (IQR 2) in the comparison group. These indicators were 1 (IQR 2), 3 (IQR 2), and 2 (IQR 1) for cytoplasmic expression and 5 (IQR 4), 2 (IQR 3), and 3 (IQR 2) for membranous-cytoplasmic one. CONCLUSION: The number of SSTR-2-expressing cells was significantly smaller in the patients with Crohn's disease than that in those with the unchanged mucosa and in those with indeterminate (unclassified) colitis. There were three SSTR2 staining types: predominantly membranous, cytoplasmic, and mixed (membranous-cytoplasmic). The cells with membranous staining appeared to be neuroendocrine, those with cytoplasmic expression were intraepithelial T lymphocytes, and those with membranous-cytoplasmic expression were both neuroendocrine and epithelial.

[Adrenocortical oncocytoma].

The paper characterizes adrenocortical oncocytoma, a rare adrenal tumor, accompanied by Cushing's syndrome and estrogen and androgen production and provides histological and immunohistochemical features. The authors describe their observation of a 33-year-old female woman. It is shown that estimation of the malignant potential of adrenocortical oncocytomas requires a special approach and must be done using the Lin-Weiss-Bisceglia criteria.

[Morphological features of oesophagogastric junction mucosa in children with gastroesophageal reflux disease].

In present work we studied the morphological features of the esophageal mucosa in 63 children with gastroesophageal reflux disease (GERD). The biopsies were taken at level of 3 cm above a Z-line and at level of 0.5-1 cm above a Z-line. The results of our study showed that the mucosa of the esophago-gastric junction may contain areas covered with columnar epithelium of 44.4% of children in the biopsies from the level of 0.5-1.0 cm above the Z-line. Inflammatory changes in the mucosa of the esophago-gastric junction identified in 71.4% of cases. The inflammation in the majority of cases (82.1%) was observed in the presence of H. pylori infection (p < 0.001). In addition, H. pylori in our study, we noted the relationship detection carditis in overweight child. When compared with the height-weight parameters, the excess body weight was observed in 17 of 28 patients. We couldn't found increasing detection of the cardia in patients with erosive GERD compared with non-erosive variants.

[Primary thyroid extranodal marginal zone lymphoma].

The paper gives the data available in the literature on the clinical and morphological features of thyroid lymphomas and on their diagnostic principles. The authors' observation details the histological and immunohistochemical characteristics of primary thyroid extranodal marginal zone lymphoma. The specific feature of the observation is total thyroid tissue substitution for tumor cells so the characteristic sign of chronic autoimmune thyroiditis were undetectable, but found only immunohistochemically from the remaining thyroid tissue follicle-like structures, which bears out the relationship between the development of lymphoma and autoimmune thyroiditis.

[Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid gland].

The paper characterizes sclerosing mucoepidermoid carcinoma with eosinophilia, a rare thyroid tumor, including histological and immunohistochemical features. The authors give their observation of a 26-year-old patient. The immunohistochemical findings (positive p63 and TTF-1 tumor cell nuclear staining) show the dual nature of a tumor arising from the cells of the ultimobranchial body and follicular epithelium.

[Morphological features of the esophagogastric transition zone at fetuses and newborns].

Morphological research of the esophagogastric transition mucosa at 35 fetuses and newborns was done. The esophagogastric transition was lined by high columnar epithelium and mucos glands. At fetuses of 22-24 week gestational age studied zone didn't have any glands. Histochemical features of the epithelium, particularly MUC5AC positive staining, corresponded to cardial type of the Barrett esophagus, defined at adults. We have revealed that mucosa of the esophagogastric transition has gastric origin and arises before birth. We found out the islets of columnar epithelium on the surface of the laminated pavement epithelium, indicated about its uneven development up to the birth. The sites of immature epithelium could be considered as transformation zones both of laminated pavement epithelium or columnar one.

[Morphological changes in esophageal mucosa in children with overweight].

In present work we studied the morphological features of the esophageal mucosa in 63 children with endoscopic diagnosis of the distal esophagitis having overweight and normal weight of a body. The biopsies were taken at level of 3 cm above a Z-line and at level of 1 cm above a Z-line. Dystrophic and dysregenerative changes were revealed at the majority of children and half of children had inflammatory changes of the esophageal mucosa regardless of weight of a body. These changes are more pronounced at level of 1 cm above a Z-line, their occurrence decreases with a distance from low esophageal sphincter. We used the pathology score system for assess the esophageal biopsies. According our scale we obtained following results: at level of 1 cm above Z-lines at 95% of children had the normal, minimum or mild features of esophagitis regardless of weight of a body. Morphological evidence of a reflux esophagitis was diagnosed statistically more often at level of 1 cm above Z lines in comparison with level of 3 cm above Z-lines (p < 0.01) as among children with overweight of the body (78 and 43% accordingly), and among children with normal weight of the body (78 and 35% accordingly). The obtained data will be allowed to avoid hyperdiagnostics of esophageal lesions in children.

[Difficulties of morphological diagnosis of inflammatory bowel disease based on the endoscopic biopsy in children].

Pathology diagnostics of inflammatory bowel diseases (IBD) in children on the material of colonobiopsies presents considerable difficulties. Definitive morphological diagnosis could be done probably no more than at half of the patients with suspicion on IBD. Diagnosis of unlassified colitis it is necessary to use to the diagnosis in more than 25% of cases. Whether at use of the given term it is desirable to specify in addition the impossibility to classify colitis between ulcerative colitis (UC) and Crohn's disease (CD) concerns or the differential diagnosis should include wider spectrum chronic colitidies. The similar situation always demands profound interdisciplinary discussion and the subsequent dynamic follow up the patient.

[A method for assessing bacterial microflora by fluorescence in situ hybridization].

The use of current diagnostic methods in a pathologist's practice, including the assessment of the bacterial microflora by the molecular microbiological technique fluorescence in situ hybridization is important and promising. The detection of bacteria and changes in the microbial flora makes it possible to clarify the nature of found morphological changes and to expand the diagnostic value of a postmortem study.

[Modernization of methods for tissue sampling and preparation for a histological study at autopsy].

Preparation of autopsy material for a histological study for correct diagnosis is not less important than that of a biopsy specimen. Based on their accumulated experience, the authors propose a number of modernizations to prepare autopsy material for the study of lung, bone marrow, and intestinal abnormalities, which require no higher work intensity, but at the same time contribute to a unified approach to investigating tissues and organs in certain pathological processes in pediatric care.

[Morphological and immunohistogenetical features of colon cancer in children].

We carried out postmortem and immunohistological studies of 3 cases of colon cancer in a 14-year-old (case 1) and an 8-year-old girl (case 2), and Turcot's syndrome in a 14-year-old girl (case 3). Tumors were located in the proximal portions of the colon and they were of rare histological types. The expression of proteins--the products of MLH 1, MHS2, and MHS6 genes responsible for DNA reparation was estimated. There was no expression of MLH1 and MHS6 in cases 2 and 3, respectively. The findings enabled the authors to assign these cases to hereditary polyposis-unassociated colonic cancer that is also a variety of Turcot's syndrome.

[Morphological features of juvenile colon polyps in children]. / Morfologicheskie osobennosti iuvenil'nykh polipov tolstoi kishki u detei.

Histological, histochemical and immunohistochemical studies of 50 solitary juvenile polyps (JP) and 50 JP from children with juvenile polyposis syndrome (JPS) were performed. Observations of the focal complex glandular structures with high mitotic rate were more frequent in JP from patients with JPS (n = 29, 58%) than in solitary JP (n = 17, 34%) (p < 0.03). The immunohistochemical study demonstrated p53 overexpression in individual cells and more than 50% of Ki-67-positive cells in 5 (10%) solitary JP and in 17(34%) JP from patients with JPS (p < 0.007). The finding of microglandular pattern is more typical for JP from patients with JPS. Pathological data, expression of p53 and Ki-67 by immunohistochemistry could help to pick out the group of JP with dysplastic changes.

[Iliac mucosa changes in late periods after total colectomy in patients with syndromes of gastro-intestinal polyposis]. / Izmeneniia slizistoi obolochki nizvedennogo segmenta podvzdoshnoi kishki v otdalennye sroki posle operatsii total'noi koléktomii u bol'nykh s sindromami polipoza zheludochno-kishechnogo trakta.

We studied follow-up iliac mucosa biopsies from 11 patients with juvenile polyposis and 4 patients with familial adenomatous polyposis who had undergone total colectomy with mucosal proctoectomy with creation of straight ileoanal anastomosis. The biopsies that have been taken from the posterior wall of the terminal ileum show incomplete and focal neocolonic transformation of iliac mucosa. Nevertheless, in most cases iliac mucosa preserved its architectural and histochemical characteristics. Chronic inflammation in iliac mucosa is not typical for patients with polyposis.