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The aim of the study was to show the possibilities of fluorescent immunocytochemistry in urgent intraoperative examination of sentinel lymph nodes in patients with early breast cancer. The authors analyzed the data on the state of the lymph nodes in 94 patients with early breast cancer who had been operated on since December 2016 to January 2018 in the Department of reconstructive plastic surgery of the breast and skin of the P.A. Herzen Moscow Oncological Institute. As a result of the use of the «Tekhnefit99ᵐTc» radiopharmaceutical during the operation, sentinel lymph nodes were isolated, the state of which was assessed by the method of urgent intraoperative cytology. In difficult-to-diagnose cases, fluorescent immunocytochemistry was used, which made it possible to avoid hypo- and overdiagnosis in 30 patients with early breast cancer. The sensitivity of the urgent cytological method for examining the sentinel lymph nodes smears was 83.3%, the specificity - 100%, the efficiency -83%, the predictive value of a positive result - 83.3%, and the predictive value of a negative result - 100%. Thus, the diagnostic accuracy of urgent cytological examination of the sentinel lymph node was 94%., Competing Interests: The authors declare no conflict of interest.

The aim of the work was to assess the possibility of the cytological method in the diagnosis of epithelial liver tumors and to determine the cytomorphological criteria in the differential diagnosis of liver carcinomas. The authors analyzed the data of 106 fine-needle aspiration biopsies and 167 smears-prints during cor-biopsy of masses of the liver in patients who were examined at the polyclinic of the oncological dispensary in Nizhny Novgorod in 2016. - 2017 As a result, full-fledged material for cytological examination in the form of smears-prints from cor-biopsy and fine-needle aspiration biopsies was obtained in 75.4% (n=126) and 95.2% (n=101), respectively. The great possibilities of the cytological method are shown: an affirmative diagnosis of the presence of primary or metastatic liver lesions was made in 88.8% (n=112) based on smears of sorbiopsy prints and in 87.1% (n = 88) with fine-needle aspiration biopsies. Typical cytomorphological criteria for primary and metastatic liver carcinomas made it possible to determine the origin of the primary tumor in 56.6% of cases (n=98)., Competing Interests: The authors declare no conflict of interest.

The purpose of this work was to show the effectiveness of the cytological method on a small number of observations, excluding all possible errors of the preanalytical stage. The paper presents several simple and easily reproducible algorithms for the cytological study of serous pleural effusions with small cellular content. On the example of 20 observations of the study of the cellular composition of serous exudates, a direct dependence of the research results on the preanalytical stage is shown. A complete study of effusion fluids in compliance with all stages of preanalytics and the use of modern methods of cytological diagnostics makes it possible to nullify the options for false-negative., Competing Interests: The authors declare no conflict of interest.

Background: Vagal paragangliomas (VPGLs) belong to a group of rare head and neck neuroendocrine tumors. VPGLs arise from the vagus nerve and are less common than carotid paragangliomas. Both diagnostics and therapy of the tumors raise significant challenges. Besides, the genetic and molecular mechanisms behind VPGL pathogenesis are poorly understood., Methods: The collection of VPGLs obtained from 8 patients of Russian population was used in the study. Exome library preparation and high-throughput sequencing of VPGLs were performed using an Illumina technology., Results: Based on exome analysis, we identified pathogenic/likely pathogenic variants of the SDHx genes, frequently mutated in paragangliomas/pheochromocytomas. SDHB variants were found in three patients, whereas SDHD was mutated in two cases. Moreover, likely pathogenic missense variants were also detected in SDHAF3 and SDHAF4 genes encoding for assembly factors for the succinate dehydrogenase (SDH) complex. In a patient, we found a novel variant of the IDH2 gene that was predicted as pathogenic by a series of algorithms used (such as SIFT, PolyPhen2, FATHMM, MutationTaster, and LRT). Additionally, pathogenic/likely pathogenic variants were determined for several genes, including novel genes and some genes previously reported as associated with different types of tumors., Conclusions: Results indicate a high heterogeneity among VPGLs, however, it seems that driver events in most cases are associated with mutations in the SDHx genes and SDH assembly factor-coding genes that lead to disruptions in the SDH complex.

A rare clinical observation of desmoid fibroma associated with a breast implant is presented. When making a morphological (cytological, histological) diagnosis at the light-optical level before surgery, a differential morphological diagnosis was performed between cicatricial changes, the stromal component of the phyloid tumor and desmoid fibroma. Only immunohistochemistry allowed us to establish a diagnosis of desmoid fibroma, since tumor cells expressed diffusely SMA, focally desmin, and most importantly, ß-catenin expression was observed in some cells., Competing Interests: The authors declare no conflict of interest.

Background: CpG island methylator phenotype (CIMP) is found in 15-20% of malignant colorectal tumors and is characterized by strong CpG hypermethylation over the genome. The molecular mechanisms of this phenomenon are not still fully understood. The development of CIMP is followed by global gene expression alterations and metabolic changes. In particular, CIMP-low colon adenocarcinoma (COAD), predominantly corresponded to consensus molecular subtype 3 (CMS3, "Metabolic") subgroup according to COAD molecular classification, is associated with elevated expression of genes participating in metabolic pathways., Methods: We performed bioinformatics analysis of RNA-Seq data from The Cancer Genome Atlas (TCGA) project for CIMP-high and non-CIMP COAD samples with DESeq2, clusterProfiler, and topGO R packages. Obtained results were validated on a set of fourteen COAD samples with matched morphologically normal tissues using quantitative PCR (qPCR)., Results: Upregulation of multiple genes involved in glycolysis and related processes (ENO2, PFKP, HK3, PKM, ENO1, HK2, PGAM1, GAPDH, ALDOA, GPI, TPI1, and HK1) was revealed in CIMP-high tumors compared to non-CIMP ones. Most remarkably, the expression of the PKLR gene, encoding for pyruvate kinase participating in gluconeogenesis, was decreased approximately 20-fold. Up to 8-fold decrease in the expression of OGDHL gene involved in tricarboxylic acid (TCA) cycle was observed in CIMP-high tumors. Using qPCR, we confirmed the increase (4-fold) in the ENO2 expression and decrease (2-fold) in the OGDHL mRNA level on a set of COAD samples., Conclusions: We demonstrated the association between CIMP-high status and the energy metabolism changes at the transcriptomic level in colorectal adenocarcinoma against the background of immune pathway activation. Differential methylation of at least nine CpG sites in OGDHL promoter region as well as decreased OGDHL mRNA level can potentially serve as an additional biomarker of the CIMP-high status in COAD.

We describe a case of lactating adenoma in pregnant woman, 32 week of gestation. Typical features of disease presented in this article was revealed by clinical and microscopic methods and it make possible to diagnose the process before operation. The diagnosis was confirmed by histological investigation of surgical material., Competing Interests: The authors declare no conflict of interest.

A case of benign proliferative formation of the mammary gland of a rare histological form - subareolar sclerosing ductal hyperplasia in combination with papillomatosis of the nipple is presented. Pathology belongs to the group of complex sclerosing lesions. When setting the morphological (cytological, histological) diagnosis, it is necessary to take into account the clinical picture - the state of the nipple-areola complex, in particular, the presence / absence of nipple discharge and its involvement in the pathological process., Competing Interests: The authors declare no conflict of interest.

Background: Neuropilin and tolloid-like 2 (NETO2) is a single-pass transmembrane protein that has been shown primarily implicated in neuron-specific processes. Upregulation of NETO2 gene was also detected in several cancer types. In colorectal cancer (CRC), it was associated with tumor progression, invasion, and metastasis, and seems to be involved in epithelial-mesenchymal transition (EMT). However, the mechanism of NETO2 action is still poorly understood., Results: We have revealed significant increase in the expression of NETO2 gene and deregulation of eight EMT-related genes in CRC. Four of them were upregulated (TWIST1, SNAIL1, LEF1, and FOXA2); the mRNA levels of other genes (FOXA1, BMP2, BMP5, and SMAD7) were decreased. Expression of NETO2 gene was weakly correlated with that of genes involved in the EMT process., Conclusions: We found considerable NETO2 upregulation, but no significant correlation between the expression of NETO2 and EMT-related genes in CRC. Thus, NETO2 may be involved in CRC progression, but is not directly associated with EMT.

The purpose of study: To determine possibilities of complex morphological diagnostic (routine cytology and histology, immunocytochemistry and immunohistochemistry, molecular genetics) of lymphoma of marginal zone. The study included 10 patients with diagnosis of lymphoma of marginal zone cells, established on the basis of application of morphological (cytological and histological), immunomorphologic (immunocytochemical and immunohistochemical) and molecular genetic techniques. The immunofenotyping was implemented using immunocytochemical technique (EnVision FLEX) applying monoclonal antibodies by DAKO manufacturer. The immunofenotyping was implemented by flow cytofluorometry technique (flow cytofluorometer FACS Calibur by Becton Dikinson, USA) using antibodies by DACO manufacturer labeled by fluorescent marks (FITC or RPE). The antibody panel included: common leukocytic antigen, common cytokeratins CD19, CD20, CD79a,CD10, Bcl2, Bcl6, CD23, CD34, TdT, CD3, CD4, CD5, CD8, CyclinD1, Ki67, κ, λ. The FISH technique was applied using probes Bcl2 FISH DNA Probe, Split Signal и MALT1 FISH DNA Probe Split Signal by DAKO manufacturer. In one patient a gene Bcl2 change was detected with purpose of differentiating diagnostic with follicular lymphoma. In three patients, diagnosing lymphoma of marginal zone was implemented by FISH technique using detection of translocation (11;18)(q21;q21), involving gene of inhibitor of apoptosis API2 and gene MALT1. The routine cytological analysis of ten cases permitted to establish an exact diagnosis of lymphoma only in five cases and with no indication that it is lymphoma of marginal zone. In two cases under routine cytological analysis only a suspicion about lymphoma was suggested. In all ten patients a positive expression of pan-B-cellular markers CD19, CD20, CD79a was observed both under immunocytochemistry and immunohistochemistry and flow cytofluorometry. In 6 patients (60%) a positive expression of gene Bcl2 was observed both under immunocytochemistry and immunohistochemistry and flow cytofluorometry. The comparison of immunocytochemistry and immunohistochemistry and flow cytofluorometry established absence of expression of CD5, CD3, CD10, CD34, CD23, Bcl6, TdT, cyclin D1. Under immunocytochemistry and immunohistochemistry in ten cases proliferative activity protein Ki-67made up no more than 30%. Under flow cytofluorometry clonality on light chains of immunoglobulins κ or λ (Igλ/Igκ) were established. Overall, correlation coefficient (r, p < 0,05) between immunocytochemistry and immunohistochemistry, flow cytofluorometry made up to 1. The four patients were applied FISH-reaction for adjustment of diagnosis. In patient with nodal lymphoma of marginal zone gene Bcl2 change was absent. In three patients with MALT-lymphoma a gene MALT1 change was established. Thereby, accuracy of routine cytological analysis at diagnosing lymphoma without indication of its type in case of lymphoma of marginal zone made up to 50%, sensitivity - 50%, specificity - 100%. The accuracy of immunofenotyping permitting diagnosing lymphoma of marginal zone made up to 100%, sensitivity - 100%, specificity - 100%. The correlation coefficient (r, p < 0,05) between data of immunocytochemistry and immunohistochemistry, flow cytofluorometry made up to 1. The accuracy, sensitivity and specificity of complex analysis (cytology, immunocytochemistry and FISH-technique) in diagnostic of lymphoma of marginal zone made up to 100%., Competing Interests: The authors declare no conflict of interest.

The analysis of cytological analysis data demonstrated that cytological diagnosis of Hodgkin's lymphoma was established properly in exact and estimated form in 92.8%. The cytological reports mentioned no alternatives. The cytological analysis system Vision Cyto® was applied to analyze cellular content by micro photos of cytological samples of 119 patients with established morphologic (histological and cytological) diagnosis of Hodgkin's lymphoma. On the basis of the received data training programs were developed concerning cytological diagnostic and detection of forms of disease. The gallery was organized concerning pictures of tumor and background cells playing key role in cytological diagnostic. The distinctive differential diagnostic indications of various forms of Hodgkin's lymphoma were established.

The major problem in prostate cancer treatment is the development of drug resistance and especially important, cross-resistance. The mechanisms of drug resistance, which are divided into ligand-dependent (requiring the presence of androgens in the cell) and independent (not requiring the presence of androgens) are reviewed. The mechanisms are mainly represented with mutations of the androgen receptor and expression of aberrant constitutively active splice variants, as well as up-regulation of genes involved in androgens synthesis.

Cell metabolic reprogramming is one of the cancer hallmarks. Glycolysis activation, along with suppression of oxidative phosphorylation and, to a lower extent, the TCA cycle, occurs in the majority of malignant tumors. A bioinformatics search for the glucose metabolism genes that are differentially expressed in colorectal cancer (CC) was performed using the data of The Cancer Genome Atlas (TCGA) Project. OGDHL for an oxoglutarate dehydrogenase complex subunit, which is involved in the TCA cycle and is indirectly responsible for the induction of apoptosis, was identified as one of the most promising candidates. A quantitative PCR analysis showed, on average, an eightfold downregulation of OGDHL in 50% (15/30) of CC samples. Based on the TCGA data, promoter hypermethylation was assumed to be a major mechanism of OGDHL inactivation. Bisulfite sequencing identified the OGDHL promoter region (+327 ... +767 relative to the transcription start site) that is often methylated in CC samples with downregulated ODGHL expression (80%, 8/10) and is possibly crucial for gene inactivation. Thus, frequent and significant OGDHL downregulation due to hypermethylation of a specific promoter region was demonstrated for CC. The OGDHL promoter methylation pattern was assumed to provide a marker for differential diagnosis of CIMP+ (CpG island methylator phenotype) tumors, which display dense hypermethylation of the promoter region in many genes.

The article discusses the results of comparative study of traditional smears and three different liquid technologies of making ready of cytological preparations (CytoSpin3, E-Prep Processor BD TriPath) using material from 112 patients with pathological processes of such different localizations as exudative liquids (31), soft tissues (22), lymphatic nodes (18), mammal glands (20), saliva glands (7), lungs (9), thyroid gland (5). It is established that under joint application of liquid and traditional cytology the effectiveness of cytological analysis increases up to 3.3%-5% depending on localization of pathologic nidus. The implementation of liquid technologies expands the possibilities of applying immunocitochemistry and molecular genetics to cytological materials.

The techniques of flow cytofluorometry and immune cytochemistry combined with routine cytological analysis were applied to 81 patients with non-Hodgkin's lymphomas to diagnose the malignant lymphomas and to determine their immune phenotypes. The accuracy of proposed techniques combination to diagnose the malignant lymphoma consists 98% and to determine the immune phenotype - 90%. The presented combination of routine cytological analysis combined with techniques of flow cytofluorometry and immune cytochemistry is the express-technique to diagnose lymphoma and its immune phenotype the day of patient visit to the doctor. This approach significantly increases the role of cytological method in diagnostics of lymphomas. The technique makes it possible to analyze simultaneously huge quantity number of lymph nodes, including deep-seated and not only the superficial lymph nodes.

The study was undertaken to define the capabilities of cytological assay in the detection of metastatic lymph node lesions. A total of 6794 lymph nodes, including 5206 fine-needle biopsy specimens of and 1588 scrapes and imprints of the lymph nodes taken from the patients operated on at the P. A. Herzen Moscow Oncological Research Institute, were analyzed. Cytological specimens were stained using the modified Pappenheim procedure (azur-eosin mixtures). The results of the cytological assay were compared with those of a planned histological examination of the lymph nodes. Overall, the accuracy of the cytological technique was 99%; false-negative and false-positive results were 0.8 and 0.2%, respectively. That of intraoperative cytological diagnosis of metastatic lymph node lesions was 99.2%. The cytological technique for examining the lymph nodes is a simple, available, and valid method of morphological diagnosis. Errors can be made in cases of micrometastases, sinus histiocytosis. There may be problems in the differential diagnosis of tumor cells and inflammatory elements.

A hundred and twenty-nine cytograms of benign tumors of the breast with different degrees of its dysplasia were morphometrically analyzed, by using a "MECOS-Ts" set for digital microscopy. The informative differentially diagnostic morphometric signs of nuclei were identified in mild, moderate, and severe epithelial dysplasias of the breast. The derived quantitative decision rules may reduce the error of a differential diagnosis of severe dysplasia by 2-3.5 times, as compared with a visual microscopy-based diagnosis.

The most informative for differential diagnosis parameters (surface and nucleus polarization) were determined on the basis of morphometric analysis of 42 cytograms of invasive duct cancer (IDC) and 39 cytograms of invasive lobular breast cancer (ILC) using the computer analyzer MEKOC-C. Combination of these two parameters allowed the authors to elaborate a decisive rule for differential diagnosis of these two cancers (the mistake is reduced to 8.6%). The analysis of 8 informative morphometric nuclear parameters has shown that in ILC the nuclei are more monomorphic, less in square and perimeter, nucleoli are less numerous than in IDC. The study gives objective criteria for preoperative differential cytological diagnosis between IDC and ILC.

Bacterial vaginosis (BV) is a highly prevalent infectious disease causing numerous complications in obstetrics, gynecology, and in the newborns. The necessity of investigating BV is explained by its increasing incidence, including its asymptomatic forms, its probable sexual transmission, and its possible role in the etiology and pathogenesis of diseases of the cervix uteri because of exposure of the squamous epithelium of the cervix uteri, permanently regenerating and therefore highly sensitive to unfavorable effects, to high concentrations of opportunistic microorganisms. Our findings indicate that women with BV, particularly those with signs of another infection, are at risk of diseases of the cervix uteri. The risk group can be detected by simple and available methods for detecting BV with obligatory cytological studies, particularly in cases with inflammatory processes, and additional tests for associated infections (chlamydiosis, herpes simplex, etc.), whose role in the pathogenesis of cervical diseases is well known.

A study was made of the cytological criteria of various degrees of radiation pathomorphosis of soft tissue cancers and sarcomas in different dose fractionation regimens and varying time of a preoperative interval. Combinations of the main and additional parenchymatous and stromal cytological signs, reflecting pathomorphosis of I-IV degrees were singled out. Schemes of cytological prediction of a direct effect of tumor radiation exposure were drawn up on the basis of regularities of changes in cellular pictures, obtained from diagnostic data before irradiation.

Two systems of cytomorphologic signs, one consisting of 40 signs and the other of 12 signs, have been compiled. The former system has been found not answering the needs of differential diagnosis. The system including 12 cytomorphologic signs carries more qualitative information and is better oriented to the tasks of differential diagnosis; another system of 8 cytomorphologic signs, permitting a differential diagnosis between severe dysplasia, preinvasive carcinoma, and Stage Ia carcinoma of the cervix uteri, has been developed on its basis.