Comprehensive approach to diagnostic cytology in endometrial pathology (review of literature).

A cytological examination of uterine cavity material has proven to be the effective method of detecting and clarifying the diagnosis of cancer and non-tumor endometrial diseases. However, sometimes there are difficulties in interpreting the results in a traditional (classical) cytological examination, due to high level of inadequate samples: the presence of mucus, a large number of blood elements, structures of poorly visible cells in the wrong preparation of the smear. At present, the method of liquid cytology, based on the technology of preparation of standard thin-layer cytological preparations from liquid cell suspension, is increasingly developed and widespread. These slides, if necessary, can be used for morphometry, cytochemical, immunocytochemical studies etc. It is also possible to prepare cell blocks from this material, and to obtain information about the histological structure if small pieces of tissue are presented in cytological material, moreover, to use these blocks for immunohistochemical reactions. Material from the uterine cavity may contain tumor cells from ovarian, tubal or other non- endometrial carcinoma, and it is necessary to obtain information about their origin, to verify the morphological diagnosis and to determine the management and treatment of patients, as a lot of problems concerning ovarian and endometrial cancer remains unclear. Examination of aspirates and scrapes from the uterine cavity using advanced molecular techniques, together with existing examination methods, can help to form risk groups for uterine, tubal, ovarian and even peritoneal tumors. The review of literature contains comparative characteristics of different methods and their combinations, which allow improving diagnostics of non-tumor lesions and endometrial tumors.

[Impressionable cytology method in diagnostics of dry eye syndrome.]

Analysis of the cellular composition of the eyeball conjunctival prints and evaluation of the informative of the cytomorphological method of research in the diagnosis of dry eye syndrome (DES). Cytological examination using impression cytology was performed in 72 patients: 60 patients with DES and 12 without eye disease (control group). The main component of cytological sample in patients with DES are (a) squamous epithelium (hyperkeratocytes); (b) groups and clusters of flattened epithelial cells; (c) a small amount (up to five in the preparation) of goblet cells. Impression cytology method improves the accuracy of diagnosis of DES.

Comparative Evaluation of ß-Catenin and E-Cadherin Expression in Liquid Aspiration Biopsy Specimens of Thyroid Nodules.

We compared the results of gene molecular and immunocytochemical studies of ß-catenin and E-cadherin in different variants of nodular thyroid disease (nodular colloid goiter, follicular thyroid adenocarcinoma, papillary thyroid cancer) and revealed changes of the function of the E-cadherin/ß-catenin complex leading to switching from adhesion function of ß-catenin in nodular colloid goiter to predominantly transcriptional activity in papillary carcinoma. The results confirm the important role of disturbances in E-cadherin-ß-catenin interactions in the mechanisms of malignant transformation of follicular epithelium.

[The technique of fluid cytology in diagnostic of thyroid diseases].

The increasing of number of diseases of thyroid actualizes searching for new solutions in differential diagnostic. Nowadays, the technique of fluid cytology is started to be applied under cytological analysis of puncture sample of thyroid. However, experience of application of technique of fluid cytology in interpretation of cytological sample is limited. The article presents results of analysis of samples of fine needle aspiration biopsy of thyroid from 126 patients. In case of traditional cytological analysis aspirate was putted on glass right away. In case of technique of fluid cytology patient was re-punctured and sample was placed into vial with preservative solution. At re-puncture increasing number of analysis with non-diagnosed samples was observed (40.6% in comparison with 17.8% under traditional cytological analysis). However, in 50% of patients with non-informative samples in traditional cytological analysis implementation of technique of fluid cytology permitted to establish proper diagnosis. In diagnostic of non-tumor affections of thyroid the best results demonstrated by technique of fluid cytology (86.6% as compared with 47.2% under technique of fluid cytology). However, in diagnostic of benign tumor affections of thyroid the best accuracy was demonstrated by traditional cytological analysis (61.1% as compared with 33.3% of technique of fluid cytology). Both techniques demonstrated similar results in category of malignant affections of thyroid. The diagnosis of cancer or suspicion to cancer was established in 85.7% of cases under technique of fluid cytology and in 82.7% of cases under traditional cytological analysis). The analysis of cytological pictures of various diseases of thyroid in technique of fluid cytology demonstrated specifics and differences from traditional cytology that are to be considered. At the same time, observations convincingly testify that in number of cases traditional and fluid techniques supplement each other. Besides, technique of fluid cytology permits preserving and transport puncture samples and in case of necessity to apply additional clarifying diagnostic techniques that in turn increases effectiveness of cytological diagnostic of affections of thyroid.

[ß-Catenin: Structure, Function and Role in Malignant Transformation of Epithelial Cells].

The article presents the data on the structure and mechanisms of ß-catenin functioning. The basic aspects of the role of ß-catenin in malignant transformation have been studied at various tumors. Primary structure of ß-catenin allows it to interact with many factors and ligands, including transcription factors, α-catenin, cadherin, Axin, Rho family GTPases, Bcl9 et al. This interaction is the base for ß-catenin's intracellular multi-functioning. The review presents data on the participation of ß-catenin in the mechanisms of adhesion, regulation of RNA metabolism, formation contacts with the cytoskeleton and its role in the canonical Wnt signaling pathway, marked examples pro-inflammatory and anti-inflammatory effects of ß-catenin. The ß-catenin involvement in malignant transformation and progression of certain tumors is not in doubt. The data on the changes in ß-catenin expression in the given examples of colon cancer, prostate cancer, different forms of thyroid cancer and hepatocellular carcinoma are presented with the prospects of its use as a marker and a predictor of malignant transformation. Continued research in this area will not only make use of ß-catenin as a potential predictor of malignant tumors, but also to develop approaches to targeted therapy.

[THE MORPHOMETRY IN CYTOLOGICAL ANALYSIS OF EXUDATIVE FLUIDS].

The cytological technique takes a leading position in diagnostic of tumor processes according exudative fluids. However, its results depend on large number of subjective factors. The morphometry is one of techniques by virtue of which objectification of data of cytological analysis is possible. The study was carried out to establish differences of morphometric parameters of benign and malignant cells of pleural effusion. The morphometric analysis of cells of mesothelium, breast cancer, adenocarcinoma of lung and adenocarcinoma of stomach was implemented. The parameters characterizing size (area, perimeter) and form (form factor) of nucleus and cell, nucleus-cytoplasm ratio. The results demonstrated that in pleural effusion between cells of proliferating mesothelium and malignant neoplasms exist significant differences in morphometric parameters (p<0.001). The differences between area of nuclei and cells are especially significant. The comparison of data of morphometry of cells of breast cancer; adenocarcinoma of lung and adenocarcinoma of stomach demonstrated that despite of some morphological similarities, analysis of morphometric parameters can provide important data for proper establishment of cytological diagnosis.

[THE VIRTUAL CYTOLOGIC SLIDES FOR EXTERNAL EVALUATION OF QUALITY OF IMPLEMENTATION OF CYTOLOGIC ANALYSES IN CLINICAL DIAGNOSTIC LABORATORIES: POSSIBILITIES AND PERSPECTIVES].

The article considers application of technology of analysis of cytological slides in external quality control of clinical diagnostic laboratories. The advantages of virtual slides are demonstrated against other applied technologies of external evaluation of quality i.e. slide plate and digital micro-photography. The conditions of formation of virtual slides for external evaluation of quality of clinical diagnostic laboratories. The technology of their application is described. The success of practical application of considered technology in the Federal system of external evaluation of quality is emphasized.

[The liquid cytology in clinical practice: a lecture].

The lecture covers one of the most perspective directions in clinical cytology. The emergence of liquid cytology is related to preparation of thin-layer specimens of organism liquids. Nowadays, the liquid cytology spreads more and more due to eephi application in different areas of cytological diagnostics, including screening of cervix uteri diseases, automatic screening, punctate tests, endoscopic and other materials. The lecture presents the basics of method, the characteristics of pre-analytic stage, the approaches to preparation of cytological specimens and cell blocks. The main possibilities, characteristics and perspectives of liquid cytology on the stage of rapid development of molecular genetic studies are discussed.

[Information technologies in clinical cytology (a lecture)].

The lecture is devoted to the urgent problem that is to increase the quality of cytological diagnosis, by diminishing the subjectivism factor via introduction of up-to-date computer information technologies into a cytologist's practice. Its main lines from the standardization of cytological specimen preparation to the registration of a cytologist's opinion and the assessment of the specialist's work quality at the laboratories that successfully use the capacities of the current information systems are described. Information technology capabilities to improve the interpretation of the cellular composition of cytological specimens are detailed.

[Proposals for standardization of clinical laboratory studies: technology "cytological study of lymph node specimens"].

This proposal contains unique requirements for a cytological study of lymph node specimens at the cytological and clinical diagnostic laboratories of health care facilities certified for this kind of work. The paper gives requirements for the performance of technologies, for specialists and auxiliary personnel, specialists' knowledge and skills, medical staff safeguarding. The conditions for rendering a service, necessary equipment, ware, and reagents are described in details. The specific features of a pre-analytical stage, methods for the fixation and staining of smears, the interpretation and recording of findings, and the control of the quality of a performed study, as well as the cost characteristics in conventional units of man-hours. The developed technology may be of great importance to the health care facilities certified for rendering this service.

Early integration of high copy HPV16 detectable in women with normal and low grade cervical cytology and histology.

BACKGROUND: Integration of human papillomavirus (HPV) DNA has been considered a late event in cervical carcinogenesis. However, integrated forms of HPV were recently detected in cancer precursor lesions using a new real time polymerase chain reaction (PCR) to detect the deletions at the 3362-3443 region of HPV16 E2 OBJECTIVE: To study the frequency of HPV16 DNA integration in cervical lesions and compare the sensitivity of an additional upstream region of the E2 ORF (2962-3138) in detecting HPV integration. METHODS: Using the TaqMan based PCR, HPV16 positive DNA samples were analysed in 164 cervical scrapings from women participating in a multicentre screening trial. Biopsy confirmation was available in 62 cases. RESULTS: Primers targeting the 3362-3443 region detected the majority of E2 deletions. In only 23% of the samples was the E2 upstream region equal or better target than the 3362-3443 region. Mixed (episomal/integrated) pattern was the most prevalent physical state of HPV16, also present in PAP smears with normal morphology. Pure integrated form was most prevalent in HSIL and cancer lesions, but also detectable in low grade abnormalities (NSIL, ASC-US, LSIL). Women with only integrated HPV16 were almost 10 years older than those with episomal HPV16. Viral load of integrated HPV16 was related to cytological abnormality (p = 0.003) but not to histology. CONCLUSIONS: Integrated HPV16 is present in low grade cervical lesions, mostly mixed with the episomal form. Women with the pure integrated form of HPV16 are older than those with the other forms.

Clearance of high-risk human papillomavirus (HPV) DNA and PAP smear abnormalities in a cohort of women subjected to HPV screening in the New Independent States of the former Soviet Union (the NIS cohort study).

BACKGROUND: We analysed the temporal relationships of the clearance of human papillomavirus (HPV) DNA and cytological abnormalities in women participating in a screening study in three NIS countries. METHODS: The 274 patients included in this analysis were prospectively followed-up for 21.6 months (range: 0.5-42.9). All 274 women had abnormal PAP test (ASC-US or higher) and high-risk HPV-positive test (HCII) at baseline. Two groups were compared: 132 women who cleared both tests (Group 1), and 142 women who cleared either HPV or abnormal PAP test (Group 2). The first clearance during the follow-up, and the last visit clearance were modeled using life-table techniques, and the predictive factors were analysed using univariate (Kaplan-Meier) and multivariate (Cox) survival analysis. RESULTS: There was no difference in the mean clearance time for the abnormal PAP test (14.4 months; 0.7-40.5 and 12.6 months; 0.5-35.0) and high-risk HPV DNA (12.67 months; 0.6-33.5 and 10.8 months; 0.7-33.4) in Group 1 and Group 2 (Mann-Whitney: P = 0.107 and P = 0.082, respectively). Clearance times for HPV DNA and abnormal PAP test did not deviate from each other in either groups (Wilcoxon: P = 0.063 and P = 0.088). The monthly clearance rates for the abnormal PAP test are 1.32 and 1.38%, and those for the HPV DNA 1.62 and 1.61%, in Groups 1 and 2, respectively. Of the factors predicting the last visit clearance, the issues related to smoking are of particular interest. CONCLUSIONS: The clearance of high-risk HPV type and abnormal PAP test shows a close temporal relationship, the former preceding the latter, however, by an interval of 1.0-2.0 months.

[Antigenic markers in the cytological diagnosis of human malignant neoplasms]. / Antigennye markery v tsitologicheskoi diagnostike zlokachestvennykh novoobrazovanii cheloveka.

The review deals with antigenic markers used for immunocytochemical diagnosis of malignant tumours describes theoretical and practical basis for identification of malignant cells in lymph nodes, bone marrow, peritoneal and pleural effusions and sputum with application of tumour markers. The identification of micrometastases in lymph nodes of patients with gastric cancer and the identification of malignant cells in smears from effusions illustrate the authors' own results. The description of immunocytochemical methods is given.

[Rapid cytological diagnosis in cancer of the lung, stomach and esophagus]. / Srochnaia tsitologicheskaia diagnostika pri rake legkogo, zheludka i pishchevoda.

The results of 1,053 express cytological examinations carried out in 369 patients were assessed. The scope and limitations of the procedure as well as errors involved were analysed. It was found that express cytological examinations provide a means for adequate evaluation of the nature and extent of cancer pathology and are instrumental in working out effective schemes of surgical treatment. An intraoperative cytological examination of lymph nodes can substitute a histological one.

[The cytological diagnosis and classification of tumorous and nontumorous lesions of the pancreas]. / Tsitologicheskaia diagnostika i klassifikatsiia opukholevykh i neopukholevykh porazhenii podzheludochnoi zhelezy.

The paper summarizes the cytologic features of tumor and non-tumor pathology of the pancreas observed in 108 cases. Cytologic examination proved highly (90%) reliable in differential diagnosis of pancreatic pathology. A cytologic classification of pancreatic lesions is suggested.

[Formalized cytological report in oncology]. / Formalizovannoe tsitologicheskoe zakliuchenie v onkologii.

A formalised report (FR) offers a set of standard phrases to be used to state (1) whether findings of a cytologic study contain new information; (2) the degree of certainty in understanding the significance of morphological forms of available international classifications of a pathology said morphological evidence is compatible with. The use of that FR provides a means of evaluating reported cytologic conclusions, and comparing them with relevant postmortem diagnosis. This makes it possible to ascertain with greater or less certainty, with which nosological forms a doctor deals. It is also a means of inspection over the way materials are sampled and processed at a particular cytological laboratory as well as evaluation of its general standards. The main advantage of introduction of FR is that it is unambiguous and can be computer processed.

[Use of leukocytic serum in treatment of shin trophic ulcers with protracted healing]. / Primenenie lekotsitarnoi syvorotki v lechenii dlitel'no ne zazhivaiushikh troficheskikh iazv goleni]

The results of treatment of 85 patients with trophic ulcers of various origin by leukocytic serum were compared with the results of treatment of 46 patients treated by routine method. The best clinical and aesthetic effect of this treatment was revealed in a group of patients with trophic ulcers due to vein varicosity. From 58 patients epithelization was detected in 49 (84,5%). The relapses of trophic ulcers in a period from 6 months to 1,5 years were revealed in 5 patients. The use of leukocytic serum ensures high percent of closure of the ulcers chiefly of venous etiology.

[Ploidic diagnosis of precancer processes and of uterine cervix cancer according to cytological parameters]. / Ploidometricheskaia diagnostika predrakovykh protsessov i raka sheiki matki po tsitologicheskim preparatam.

It is suggested, on the basis of ploidic, to define more precisely the cytological analysis according to values of the mean ploidy of cell nuclei of epitheliocytes in neoplasms of the cervix of the uterus. Ploidiometry was found to ensure a more accurate differential diagnosis of 3 process stages, i.e. benign (low degree of intraepithelial neoplasia), marginal (high degree of intraepithelial neoplasia) and malignant stages of carcinogenesis (carcinoma) in the cervix of the uterus.

[Feasibilities of cytological diagnosis in the static telepathology mode]. / Vozmozhnosti tsitologicheskoi diagnostiki v staticheskom rezhime telepatologii.

Results of cytological diagnosis in the static telepathology mode are analyzed. Three expert cytologists made the diagnosis on the basis of images of cytological preparations obtained from 94 patients with tumors of soft tissues and bones. A total of 113 diagnoses were correct: benign or malignant type of the tumor and its histological type were identified. In general, a total of 152 (88.9%) diagnoses were correct as regards their significance for treatment strategy. Errors classified as groups 3 and 4 were the most significant (erroneous assessment of tumor type--benign or malignant--in 6.4% cases). Analysis of discrepancies between cytological and pathoanatomical diagnoses and data of routine optic microscopy of similar cytological preparations of the same material (bone and soft tissue tumors) showed the same value: 6.8% of cytological and pathoanatomical diagnoses were at disagreement (groups 3 and 4 of errors). Therefore, telepathology can be resorted to for consultations and discussion of obscure cases. It is particularly important for a morphologist to discuss complex cases by means of telepathology at a specialized institution, distant from him or her.