[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.

[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.

[A rare case of a functioning gonadotroph tumor accompanied by erythrocytosis in an elderly man].

Functioning gonadotroph adenomas are rare pituitary tumors secreting one or two gonadotropins (follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH)), which are hormonally active. In the majority of cases, gonadotroph tumors are endocrinologically "silent" and make up more than a half of non-functioning pituitary adenomas. In this article we describe a rare clinical case of LH/FSH-secreting pituitary macroadenoma with bitemporal hemianopsia in a 62-year-old man. The patient underwent transnasal transsphenoidal adenomectomy, leading to remission. The distinctive feature of this case is the presence of secondary erythrocytosis due to endogenous hyperandrogenism, which required several blood exfusions to normaliza the level of hematocrit before surgery. It is noteworthy that clinical signs of erythrocytosis were present long before visual impairment. This clinical case demonstrates difficulties in the early diagnosis of functioning gonadotroph adenomas.

[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.

[Immunohistochemical study on the expression/hyperexpression of aberrant/eutopic receptors in patients with bilateral macronodular adrenal hyperplasia].

Bilateral macronodular adrenal hyperplasia (BMAH) is a rare cause of Cushing's syndrome. In this case cortisol production can be regulated by both genetic factors and various molecular mechanisms. The presence of aberrant or overexpression of eutopic receptors on the membrane of adrenal cortex may lead to activation of cAMP/PKA signaling pathways and consequently, pathological stimulation of steroidogenesis. Since proving the effectiveness of unilateral adrenalectomy in BMAH by achievement of stable remission, preoperative clinical and laboratory tests (ligand-induced tests) are no longer of relevant. Nevertheless, in the absence of normalization of the level of cortisol in the postoperative period or its recurrence, subsequent specific targeted medical options can be offered only if expression/hyperexpression predominance of one or another receptor. Their detection becomes possible using more reliable diagnostic methods such as polymerase chain reaction (PCR) and immunohistochemical studies (IHC) than clinical laboratory tests. At the moment, PCR has gained a wider application. This article summarizes data on the use of immunohistochemical study in BMAH.

[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.

[Histopatological and molecular genetic characteristics of clinically aggressive variants of papillary thyroid carcinoma]. / Gistologicheskaia i molekuliarno-geneticheskaia kharakteristika klinicheski agressivnykh variantov papilliarnogo raka shchitovidnoi zhelezy.

Papillary carcinoma is the most commonly diagnosed form of well-differentiated thyroid cancer that is generally characterized by a favorable prognosis. However, a number of relatively rare variants of this tumor, such as papillary carcinoma of high cells, papillary carcinoma of columnar cells, a diffuse sclerosing variant and recently described cancer of shoe nail cell type, are characterized by a less favorable clinical course, a high frequency of distant metastasis, and relatively low overall and relapse-free survival rates. In this connection, it is important to recognize these options at the stage of a primary morphological study. This review of the literature considers the morphological, clinical and molecular genetic features of the above variants of papillary thyroid carcinoma.

[Ectopic ACTH-syndrome caused by neuroendocrine tumor of lung]. / AKTG-éktopicheskii sindrom pri neiroéndokrinnoi opukholi legkogo.

Ectopic ACTH-syndrome is a relatively rare neuroendocrine disease. It is characterized by hypercortisolemia-associated severe complications that justifies need for timely diagnosis and radical therapy. Case report of young patient with ACTH-producing lung tumor is presented. There was 1-year diagnostic search on background of endogenous hypercorticism. Treatment resulted severe postoperative adrenal insufficiency that demonstrates current difficulties in management of these patients.

[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.

[Telomerase reverse transcriptase (TERT) promoter mutations in the tumors of human endocrine organs: Biological and prognostic value].

The analysis of the data available in the literature has shown that telomerase reverse transcriptase TERT promoter may serve as promising markers of malignancy, aggressive disease course, and poor prognosis for malignant tumors of endocrine organs. Considering the established association of mutations with tumors having a poor prognosis (high-grade and anaplastic carcinoma of the thyroid), it is reasonable to perform prognostic-value investigations in a group of low-grade thyroid carcinomas that may occasionally recur and may be resistant to radioactive iodine therapy, i.e. can demonstrate a poor course and prognosis. TERT promoter mutations may be a specific marker of the clinically aggressive forms of adrenocortical carcinoma, but the determination of its diagnostic value calls for additional investigations that will have the larger number cases and establish the association with clinical features and survival rates.

[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.

THE ROLE OF THE NEUROENDOCRINE SYSTEM IN THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE.

Ulcerative colitis and Crohn's disease are both characterized by chronic, relapsing intestinal inflammation. The aetiology of both forms of inflammatory bowel disease (IBD) is still unknown. A potentially interesting area is the immunoregulatory role of enteric neuroendocrine system and neuroendocrine cells. Neuropeprides, like substance F', somatostatin, vasoactive intestinal peptide and calcitonin gene related peptide, are the molecular mediators of neuroregulation of the intestinal immune system, providing for interactions between nervous system and imniunocytes. In this review the role of neuroendocrine system and its neuroimmune modulators in IBD will be highlighted, together with their possible future use in the treatment of IBD.

[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.

[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.