Search

We resequenced and phased 27 kb of DNA within 580 kb of the MHC class II region in 158 population chromosomes, most of which were conserved extended haplotypes (CEHs) of European descent or contained their centromeric fragments. We determined the single nucleotide polymorphism and deletion-insertion polymorphism alleles of the dominant sequences from HLA-DQA2 to DAXX for these CEHs. Nine of 13 CEHs remained sufficiently intact to possess a dominant sequence extending at least to DAXX, 230 kb centromeric to HLA-DPB1. We identified the regions centromeric to HLA-DQB1 within which single instances of eight "common" European MHC haplotypes previously sequenced by the MHC Haplotype Project (MHP) were representative of those dominant CEH sequences. Only two MHP haplotypes had a dominant CEH sequence throughout the centromeric and extended class II region and one MHP haplotype did not represent a known European CEH anywhere in the region. We identified the centromeric recombination transition points of other MHP sequences from CEH representation to non-representation. Several CEH pairs or groups shared sequence identity in small blocks but had significantly different (although still conserved for each separate CEH) sequences in surrounding regions. These patterns partly explain strong calculated linkage disequilibrium over only short (tens to hundreds of kilobases) distances in the context of a finite number of observed megabase-length CEHs comprising half a population's haplotypes. Our results provide a clearer picture of European CEH class II allelic structure and population haplotype architecture, improved regional CEH markers, and raise questions concerning regional recombination hotspots.

Objective Endometrial cytology has been widely used as a screening tool in Japan. Traditionally, a three-tier reporting system, consisting of 'negative', 'suspicious' and 'positive' categories, has been used. However, a more descriptive system, the New Terminology in Endometrial Cytology ( NTEMC), which is based on the Bethesda System for uterine cervical cytology, was introduced recently. The objective of this study was to validate the NTEMC criteria. Methods Endometrial cytology specimens that had been categorised as 'suspicious' were collected in our hospital between 2003 and 2013, and from these, 106 specimens with corresponding histological results, were re-evaluated according to the NTEMC criteria. Diagnostic categories were assigned based on that chosen by the majority of the examining members. Results Negative, atypical endometrial cells, of undetermined significance ( ATEC- US), atypical endometrial cells for which atypical endometrial hyperplasia or worse cannot be excluded ( ATEC-A), endometrial hyperplasia, atypical endometrial hyperplasia and malignancy were selected as the diagnostic categories for 9 (8.5%), 34 (32.1%), 17 (16%), 34 (32.1%), 5 (4.7%) and 7 (6.6%) specimens, respectively. Corresponding histological categories of benign, endometrial hyperplasia, atypical endometrial hyperplasia and malignancy were established in 28 (82.4%), 1 (2.9%), 2 (5.9%) and 3 (8.8%) ATEC- US specimens, respectively, and in 6 (35.3%), 3 (17.6%), 2 (11.8%) and 6 (35.3%) ATEC-A specimens, respectively. The histological category distribution differed significantly ( P = 0.001), and there was a significant correlation between corresponding cytological and histological categories ( P = 0.005). Conclusion The ATEC category of NTEMC system works well in a practical setting and resembles the Bethesda reporting system ASC (atypical squamous cells) category for cervical cytology. [ABSTRACT FROM AUTHOR]

Objective The purpose of the present study was to evaluate the reproducibility of the cytological diagnosis of endometrial lesions by the Osaki Study Group ( OSG) method of new cytological diagnostic criteria using BD SurePath™( SP)-liquid-based cytology ( LBC). Methods This cytological classification using the OSG method consists of six categories: (i) normal endometrium ( NE), (ii) endometrial glandular and stromal breakdown ( EGBD), (iii) atypical endometrial cells, cannot exclude atypical endometrial hyperplasia or more ( ATEC-A), (iv) adenocarcinoma including atypical endometrial hyperplasia or malignant tumour (Malignancy), (v) endometrial hyperplasia without atypia ( EH) and (vi) atypical endometrial cells of undetermined significance ( ATEC- US). For this study, a total 244 endometrial samplings were classified by two academic cytopathologists as follows: 147 NE cases , 36 EGBD cases , 47 Malignant cases, eight ATEC-A cases, two EH cases and four ATEC- US cases. To confirm the reproducibility of the diagnosis and to study the inter- and intra-observer agreement further, a second review round followed at 3-month intervals, which included three additional cytopathologists. Results The inter-observer agreement of NE classes improved progressively from 'good to fair' to 'excellent', with values increasing from 0.70 to 0.81. Both EGBD and Malignancy classes improved progressively from 'good to fair' to 'excellent', with values increasing from 0.62-0.63 to 0.84-0.95, respectively. The overall intra-observer agreement between the first and the second rounds was 'good to fair' to 'excellent', with values changing from 0.79 to 0.85. All kappa improvements were significant ( P < 0.0001). Conclusion In this study, it seemed that the use of the OSG method as the new diagnostic criteria for SP- LBC preparation, may be a valid method to improve the precision (reproducibility) of endometrial cytology. [ABSTRACT FROM AUTHOR]

Background and Objective: In endometrial cytology, differentiating endometrial glandular stromal breakdown (EGBD) from endometrial endometrioid carcinoma (G1-EEC) is often difficult. In this study, we provided a new focus on chondroitin sulfate (CS), a major substrate component of the endometrial stroma, and assessed the diagnostic utility of Alcian Blue (AB) staining in the differential diagnosis in liquid-based cytological (LBC) samples., Materials and Methods: LBC specimens from 19 patients with a proliferative endometrium, 36 with EGBD, and 30 with G1-EEC who underwent endometrial cytology were stained with AB (pH 1.0), and their reactivity was observed. In addition, immunocytochemical staining of CS and CD31 was performed for five cases each to evaluate their interrelationship with blood vessels., Results: Regarding the 30 G1-EEC cases, at least one of the three representative staining patterns was observed by AB staining: dot-like, microtubular, and finely branched linear patterns. Moreover, the inner portion of the tubular material observed by AB staining expressed CD31. Conversely, in the 36 EGBD cases, only five metaplastic clusters with irregular protrusions and condensed stromal clusters (CSCs) showed a dot-like positive pattern, and background CSCs did not show reactivity to AB staining in any of the cases. Furthermore, the vascular structure expressing CD31 in cell clusters was also unclear., Conclusions: We demonstrated that AB staining shows different staining patterns in G1-EEC and EGBD, reflecting their different tissue structures. Our data provide new insights into endometrial cell diagnosis changes and demonstrate that AB staining is a potential new diagnostic aid tool for the differentiation of G1-EEC from EGBD., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Cytology.)

Our goal was to compare the treatment outcomes of open-abdominal radical hysterectomy (O-RH) and total laparoscopic hysterectomy (TLRH) with vaginal cuff creation and without using a uterine manipulator in stage IB1-B2 (tumor size < 4 cm) cervical cancer cases. In this retrospective multicenter analysis, 94 cervical cancer stage IB1-B2 patients who underwent O-RH or TLRH in six hospitals in Japan between September 2016 and July 2020 were included; 36 patients underwent TLRH. Propensity score matching was performed because the tumor diameter was large, and positive cases of lymph node metastases were included in the O-RH group due to selection bias. The primary endpoint was progression-free survival (PFS) and recurrence sites of TLRH and O-RH. PFS and OS (overall survival) were not significant in both the TLRH (n = 27) and O-RH (n = 27) groups; none required conversion to laparotomy. The maximum tumor size was <2 and ≥2 cm in 12 (44.4%) and 15 (55.6%) patients, respectively, in both groups. Reportedly, the TLRH group had lesser bleeding than the O-RH group (p < 0.001). Median follow-up was 33.5 (2−65) and 41.5 (6−75) months in the TLRH and O-RH groups, respectively. PFS and OS were not significantly different between the two groups (TLRH: 92.6%, O-RH: 92.6%; log-rank p = 0.985 and 97.2%, 100%; p = 0.317, respectively). The prognosis of early cervical cancer was not significantly different between TLRH and O-RH. Tumor spillage was prevented by creating a vaginal cuff and avoiding the use of a uterine manipulator. Therefore, TLRH might be considered efficient.

Introduction: In Japan, the direct smearing preparation (conventional preparation) has been widely used for cytological examination of the endometrium. Problems with the conventional preparation can be dissolved by liquid-based cytology (LBC) preparation. The Yokohama System is a method for reporting endometrial cytology, but the system lumps cancers together and does not distinguish between histological types. The objective of this study was to clarify morphometrical differences among endometrial endometrioid carcinoma grade 1 (G1), grade 3 (G3), and serous carcinoma (Serous) by image analysis of endometrial LBC., Methods: Using Papanicolaou smears prepared by LBC after sampling with a brush from 32 G1, 16 G3, and 16 Serous patients, image analysis was performed concerning the following 11 items: (1) number of layers of cluster, (2) area of cluster, (3) perimeter of cluster, (4) roundness of cluster, (5) complexity of cluster, (6) area of nucleus, (7) perimeter of nucleus, (8) roundness of nucleus, (9) complexity of nucleus, (10) area of nucleolus, and (11) nucleolus/nucleus (N/N) ratio. The data were statistically compared among G1, G3, and Serous., Results: Significant differences were observed in the number of layers of cluster (G1G3G3, G1>Serous), complexity of cluster (G1Serous), and N/N ratio (G1>G3, G3

Objective: In this study, we aimed to retrospectively investigate and confirm whether atypical nuclear findings in endometrial cytology are useful when assessed by image morphometry in liquid-based cytology (LBC) and compared with microscopic evaluation., Methods: In total, 53 cases were selected for this study, including 11 presenting proliferative endometrium, 12 with surface papillary syncytial change with endometrial glandular and stromal breakdown (EGBD-SPSC), 10 endometrioid carcinoma grade 1 (G1-EEC), 10 EEC grade 3 (G3-EEC), and 10 endometrial serous carcinomas (ESC). Nuclear image morphometry for nuclear geometric features (area, grey value, aspect ratio, internuclear distance, nucleolar diameter) was performed using ImageJ computer software. For assessing nucleoli, 3861 nuclei were measured, and for nuclear findings, except for nucleoli, 4036 nuclei were measured in total., Results: (a) Compared with G1-EEC, G3-EEC and ESC presented a marked increase in all six parameters (nuclear enlargement, anisonucleosis, nuclear shade, nuclear shape, irregularity of nuclear arrangement, and nucleolar size). (b) EGBD-SPSC presented a marked increase in two parameters (nuclear shade, nuclear shape) when compared with G1/G3-EEC and ESC. (c) Compared with EGBD-SPSC, EEC and ESC demonstrated a marked increase in nucleolar size (≥2.0 μm). (d) ESC presented a marked increase in nucleolar size (≥3.0 μm) when compared with G3-EEC., Conclusions: Here we confirmed that atypical nuclear findings evaluated by image morphometry are as useful as microscopic evaluations in endometrial cytology. We believe that the objective evaluation of nucleolar size could contribute to an accurate diagnosis of endometrial-LBC samples., (© 2020 John Wiley & Sons Ltd.)

The adoption of endometrial cytology as a diagnostic procedure has been hampered in the past by difficulties arising in interpreting the cellular findings due to a number of factors (such as excess blood, cellular overlapping, and the complex physiology of endometrium). Recently, the use of liquid-based cytology (LBC), with its ability to remove blood and mucus and to distribute cells uniformly in a thin layer on the slide, has provided an opportunity to reevaluate the role of endometrial cytology. LBC samples are easier to screen compared to conventional ones, due to a smaller screening area and an excellent quality of cell preparations. LBC by using peculiar cytoarchitectural features is a useful tool in the cellular diagnosis and follow-up of abnormalities, which, however, remains complementary to histopathology and to the emerging molecular diagnostic cytopathology. This review discusses these various entities and takes into consideration the ancillary techniques that may be useful in the diagnostic procedure. Herein, we also summarize the process and rationale by which updates were made to the standardized terminology in 2018 and outline the contents of the new Bethesda-style classification (the Yokohama system) for the endometrial cytology., (© 2019 S. Karger AG, Basel.)

Objective: This study evaluated cellular adequacy in endometrial liquid-based cytology (LBC) specimens., Methods: In total, 1267 cases were obtained and the rate of unsatisfactory specimen and diagnostic accuracy for malignancy were assessed. If ≥10 cellular clusters composed of ≤30 endometrial cells were found per specimen, then the sample was provisionally considered adequate., Results: The unsatisfactory rate (with fewer than 10 clusters) was 15.4%. Diagnostic accuracy in specimens with ≥10 clusters was significantly higher (90.5% vs 36.4%) than that in specimens with fewer than10 clusters. Moreover, the unsatisfactory rate in patients aged ≥60 years was significantly higher (33.8% vs 13.2%) than that in patients younger than 60 years. Although the unsatisfactory rate was decreased, significant differences were not found between cases with fewer than five clusters (22.6%) and fewer than 10 clusters (33.8%) in patients aged ≥60 years. Diagnostic accuracy in cases with five or more clusters was significantly higher (90.3% vs 0%) than that in cases with fewer than five clusters., Conclusions: We propose that ≥10 clusters with ≥30 endometrial cells per cluster could be used as a specimen adequacy criterion for endometrial LBC. If ≥10 clusters cannot be found in patients aged ≥60 years, then the use of the alternative criterion of five or more clusters may yield satisfactory specimen adequacy., (© 2019 John Wiley & Sons Ltd.)

Introduction: This study evaluated the immunocytochemical (ICC) expression of IMP3 in direct endometrial brushings processed as liquid-based cytology (LBC) samples of endometrioid adenocarcinoma (EAC), serous carcinoma (ESC) and surface papillary syncytial change (SPSC) with endometrial glandular and stromal breakdown (EGBD) to exploit its possible differential diagnostic aid., Methods: In total, 333 samples of LBC samples were obtained from selected outpatients in parallel with Pipelle endometrial sampling. They consisted of 97 EAC (83 grade 1: EAC-1, 14 EAC-3), 35 ESC and 201 benign endometrial samples (51 proliferative, 42 secretory, 38 atrophic, 70 SPSC with EGBD). ICC expression of insulin-like growth factor-II mRNA-binding protein 3 (IMP3) was manually performed on Papanicolaou-stained LBC samples., Results: The ESC samples showed positive staining cells in 100%, EAC-3 in 28.5%, and EAC-1 in 2.4% cases. All the benign endometrium samples were negative. Only ESC cases showed strong immunoreactivity (≥3+) in more than 50% of tumour cells with an average frequency of 80%., Conclusions: IMP3 is a helpful immunomarker to distinguish ESC from EAC and SPSC in endometrial cytology., (© 2019 John Wiley & Sons Ltd.)

Objective: We conducted a prospective, multicentre study to compare the clinical performance of liquid-based endometrial cytology (LBEC) using SurePath™ with that of suction endometrial tissue biopsy (SETB). This study is officially advocated and reported by the Japan Association of Obstetricians and Gynecologists. By publishing our midterm data, we intend to disseminate the benefits of LBEC system, using the descriptive reporting format and algorithmic interpretational approach., Methods: From April 2014 to December 2015, we consecutively assessed 1116 LBEC specimens and 1044 SETB specimens in our five outpatient clinics., Results: The sensitivity of suction tissue biopsies was 85.2%, whereas the sensitivity of LBEC was 92.2%. The specificity of suction tissue biopsies was 98.9% and that of LBEC was 98.5%. The negative predictive value of LBEC (99.1%) was higher than that of SETB (98.1%), although the difference between these values was not significant., Conclusions: The clinical performance of LBEC for detecting endometrial malignancies was almost identical to the performance of SETB. This indicates that LBEC was not inferior to SETB for the detection of endometrial cancer. The LBEC is appropriate for various clinical situations as the first-step detecting tool. In addition, it could be used for cancer surveillance for women with signs highly suggestive of endometrial malignancies and in Lynch syndrome patients, on a larger scale., (© 2018 John Wiley & Sons Ltd.)

Background: The main purpose of directly sampled endometrial cytology is to detect invasive endometrial malignancies. With this principle in mind, The Yokohama System (TYS) Working Group, composed of cytopathologists, surgical pathologists, and gynecologic oncologists met at the 2016 International Congress of Cytology, Yokohama, with the aim to publish a standardized reporting system inclusive of specific diagnostic categories and cytomorphologic criteria for uniform and reliable diagnosis of endometrial malignancies on directly sampled endometrial samples., Methods: The diagnostic cytopathologic criteria previously published in the literature by the Japanese and Greek working group on endometrial cytology (Yanoh et al. [2012] Acta Cytol. 56:233; Margari et al. [2016] Diagn Cytopathol. 44:888-901) were critically reviewed with the aim of correlating the diagnostic classes to well defined risk categories for endometrial carcinoma (EC). Moreover, two classes of "atypical" endometrial cells were correlated respectively to a low- and high risk group. Some methodological suggestions for the application of ancillary special technologies to liquid based samples were also given., Results: The TYS group conceived a new Bethesda-style classification for directly sampled endometrial cytology which correlates the cytologic diagnostic classes with definite risk categories. The cytomorphologic findings have been correlated to the molecular pathology of EC, also through the application of ancillary special techniques to liquid-based samples., Conclusions: The success of TYS will depend on the acceptance of TYS by all the relevant pathology and gynecologic oncology communities who, by their joint efforts, will adopt, critically evaluate, and optimize this method with the only aim of further improving the impact of endometrial cytology on patients' care., (© 2018 Wiley Periodicals, Inc.)

Objective: The purpose of the present study was to evaluate the reproducibility of the cytological diagnosis of endometrial lesions by the Osaki Study Group (OSG) method of new cytological diagnostic criteria using BD SurePath ™ (SP)-liquid-based cytology (LBC)., Methods: This cytological classification using the OSG method consists of six categories: (i) normal endometrium (NE), (ii) endometrial glandular and stromal breakdown (EGBD), (iii) atypical endometrial cells, cannot exclude atypical endometrial hyperplasia or more (ATEC-A), (iv) adenocarcinoma including atypical endometrial hyperplasia or malignant tumour (Malignancy), (v) endometrial hyperplasia without atypia (EH) and (vi) atypical endometrial cells of undetermined significance (ATEC-US). For this study, a total 244 endometrial samplings were classified by two academic cytopathologists as follows: 147 NE cases , 36 EGBD cases , 47 Malignant cases, eight ATEC-A cases, two EH cases and four ATEC-US cases. To confirm the reproducibility of the diagnosis and to study the inter- and intra-observer agreement further, a second review round followed at 3-month intervals, which included three additional cytopathologists., Results: The inter-observer agreement of NE classes improved progressively from 'good to fair' to 'excellent', with values increasing from 0.70 to 0.81. Both EGBD and Malignancy classes improved progressively from 'good to fair' to 'excellent', with values increasing from 0.62-0.63 to 0.84-0.95, respectively. The overall intra-observer agreement between the first and the second rounds was 'good to fair' to 'excellent', with values changing from 0.79 to 0.85. All kappa improvements were significant (P < 0.0001)., Conclusion: In this study, it seemed that the use of the OSG method as the new diagnostic criteria for SP-LBC preparation, may be a valid method to improve the precision (reproducibility) of endometrial cytology., (© 2016 John Wiley & Sons Ltd.)

Objective: To evaluate the efficacy of the automated screening system FocalPoint for cervical cytology quality control (QC) rescreening. False-negative rates (FNRs) were evaluated by a multi-institutional retrospective study., Study Design: Cervical cytology slides that had already been reported as negative for intraepithelial lesion or malignancy (NILM) were chosen arbitrarily for FocalPoint rescreening. Slides stratified into the highest 15% probability of being abnormal were rescreened by a cytotechnologist. The slides that were abnormal were reevaluated by a cytopathologist to be false negatives., Results: Rescreening of 12,000 slides, i.e. 9,000 conventional slides and 3,000 liquid-based cytology (LBC) slides, was performed; 9,826 (7,393 conventional and 2,433 LBC) were satisfactory for FocalPoint (2,174 were determined unsatisfactory) and those within the highest 15% of probability (1,496, i.e. 1,123 conventional and 373 LBC) were rescreened. As a result, 117 (96 conventional and 21 LBC) were determined as abnormal (other than NILM) and the FNR was 1.19%. Among these 117 slides, 40 (35 conventional and 5 LBC) were determined as high-grade squamous intraepithelial lesion and greater (HSIL+)., Conclusion: Of 117 (1.19%) abnormal slides detected, 40 (0.41%) were determined to be HSIL+. This result suggests that FocalPoint is effective for QC rescreening of cervical cytology., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Objective: To evaluate the sensitivity and specificity of the BD SurePath™ liquid-based Papanicolaou test for assessing the cytology of intrauterine endometrial samples according to newly devised cytological diagnostic criteria and a novel descriptive reporting format., Materials and Methods: One hundred and twenty-two endometrial samples were analyzed. All samples were obtained directly from the intrauterine cavity using the Uterobrush or Honest Super Brush. The samples used for the histological examination and cytological tests were collected simultaneously. Our study group devised new cytological diagnostic criteria for examining endometrial samples: the Osaki Study Group method. In this study, histological diagnosis was considered to be the gold standard for cytological diagnosis. A novel descriptive reporting format was also used., Results: Satisfactory cytological specimens were obtained in all cases. The sensitivity and specificity of the SurePath endometrial cytological examination method were 96.4 and 100%, respectively., Conclusion: These results indicate that the SurePath method is acceptable for clinical use. Since the SurePath method seems to be easier and allows greater preparation standardization than the conventional method, coupling it with our newly devised cytological diagnostic criteria and descriptive reporting format might represent a reliable diagnostic method for assessing endometrial specimens.

We compared the cytoarchitectural features used for the cytologic diagnosis of endometrial adenocarcinoma (EC) using ThinPrep® (TPS = ThinPrep Sample) and BD SurePath™ (SPS = SurePath Sample) preparations. In 20 patients, a direct endometrial sample using the Uterobrush was obtained. Nineteen cases of EA and one case of carcinosarcoma were studied. TPS and SPS were performed according to the manufacturer's recommendations. Moreover, after the TPS preparation, the residual material was also used to prepare an SPS sample (TP-SPS = ThinPrep-Surepath sample). The following points were investigated in both preparations: (1) number of cell clumps; SPS had a significantly higher (20.9) than TPS (1.7) and TP-SPS (10.3); (2) long axis of clumps; SPS had a significantly higher (215.4) than TPS (146.0); (3) rate of cell clumps with longer axes than 200 μm; SPS had a significantly higher (36.7) than TPS (15.2) and TP-SPS (24.2). TP-SPS showed higher values than TPS; (4) nuclear area; TPS had a significant higher (61.2) than SPS (40.8) and TP-SPS (38.6); (5) degree of overlapping nuclei; SPS (3.4) had a significantly higher number of overlapping nuclei than TPS (0.7) and TP-SPS (2.1); (6) nuclear chromatin pattern; no significant differences for the nuclear chromatin pattern were found in the three different methods. The poor performance of TPS versus SPS and TP-SPS was explained with the heavy blood contamination of the samples, and the absence of adhesive coating in the slides is used for TPS. Further investigation of technical differences in liquid-based cytology methodologies is needed., (Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.)

It is well known that "condensed cluster of stromal cells (CCSC)" and "metaplastic clumps with irregular protrusion (MCIP)" in endometrial glandular and stromal breakdown (EGBD) cases may simulate "clumps of cancer cells (CCC)" in endometrioid adenocarcinoma grade 1 (G1), leading to difficulty in cytological interpretation. The aim of this study was undertaken to clarify the cytological immunoreactivity of nuclear findings about CCSC and MCIP which may be recognized in EGBD cases by using p53 protein and cyclin A in liquid-based cytologic (LBC) preparations. The material consists of cytologic smears of 20 cases of EGBD and 20 cases of G1 for which histopathological diagnosis was obtained by endometrial curettage at the JA Suzuka General Hospital. The evaluation of immunoreactivity was performed by using the intensity of nuclear staining and the nuclear labeling index (N-LI). The intensity of nuclear staining was scored as negative (0), weak (1), moderate (2), or strong (3). The N-LI was scored as less than 10% (0), from 10 to 25% (1), from 26 to 50% (2), or greater than 50% (3). The final score was calculated of the addition of both partial scores. Results are as follows: As for the p53 protein immunoreactivity, CCC (2.4 ± 1.4) was a significantly higher value in comparison with CCSC (0) and MCIP (0.8 ± 0.4), respectively. As for the cyclin A immunoreactivity, CCC (2.8 ± 1.1) was a significantly higher value in comparison with CCSC (0) and MCIP (0.6 ± 0.5), respectively. CCSC and MCIP in EGBD are misunderstood as cellular atypia and structural atypia on occasion; but, as for results of the immunoreactivity scores of p53 protein and cyclin A in our study, it seemed that those biochemical characters proved that the biological activity level was low (or degenerative). The results of the current study demonstrated that the cytological immunoreactivity of nuclear findings by p53 and cyclin A appear to be more useful for the LBC assessment of endometrial lesions, especially for the discrimination of EGBD and G1., (Copyright © 2011 Wiley Periodicals, Inc.)

The aim of this study was to assess the utility of liquid-based cytologic preparation (LP) compared with conventional preparation (CP) for the assessment of nuclear findings in endometrial glandular and stromal breakdown (EGBD) which may be misdiagnosed as carcinoma in EGBD cases. The material consists of cytologic smears including 20 cases of proliferative endometrium (PE), 20 cases of EGBD, and 20 cases of endometrioid adenocarcinoma grade1 (G1) for which histopathological diagnosis was obtained by endometrial curettage at the JA Suzuka General Hospital. Nuclear findings were examined in PE cells, EGBD-stromal cells, EGBD-metaplastic cells, and G1 cells, respectively. It was examined about the following items; (1) nuclear shape; (2) A long/minor axis ratio in cell nuclei; (3) an area of cell nuclei; (4) overlapping nuclei. Results are as follows: (1) nuclear shape; as for the reniform shape of EGBD-stromal cells and spindle shape of EGBD-metaplastic cells, the ratio of the LP method was a higher value than the CP method. (2) The long axis and area of cell nuclei; LP in all groups was a recognizable tendency for nuclear shrinkage. (3) The long/minor axis ratio in cell nuclei; only EGBD-metaplastic cells recognize a significant difference between CP and LP. (4) Overlapping nuclei; LP was a higher value in comparison with CP in the other groups except PE cells, and the degree of overlapping nuclei was enhanced about three times. Therefore, although a cell of LP has a shrinking tendency, (1) it is excellent that LP preserves a characteristic of nuclear shape than CP; (2) a cellular characteristic becomes clearer, because three-dimensional architecture of LP is preserved of than CP. As for the standard preparation method for endometrial cytology samples, we considered that a concrete introduction of the LP method poses no problems., (Copyright © 2011 Wiley Periodicals, Inc.)

Objective: Liquid-based preparation (LBP) of the endometrial lesions is an important diagnostic tool for a variety of endometrial abnormalities because of its simplicity and high quali-quantitative diagnostic yield. We aimed to investigate the LBP method for endometrial cytology to evaluate both benign and abnormal endometrial lesions., Study Design: LBP is a semiautomated methodology that has recently become widely available and has gained popularity as a method of collecting and processing both gynecologic and nongynecologic cellular specimens., Results: Some peculiar endometrial cytoarchitectural features were described using LBPs. These were advantageous to screen as compared to conventional slides due to a smaller screening area and an excellent quality of cell preparations., Conclusions: LBP is a useful tool in the cellular diagnosis and follow-up of endometrial abnormalities, which remains complementary to the emerging molecular diagnostic cytopathology. The study of LBPs from endometrial cytology could be challenging since it is affected by numerous look-alikes and diagnostic pitfalls. This review discusses these various entities and takes into consideration the ancillary techniques that may be useful in the diagnostic procedure.

This study was to clarify the nuclear features of "condensed clusters of stromal cells (EGBD-stromal cells)" and "metaplastic clumps with irregular protrusions (EGBD-metaplastic cells)" which may be recognized in endometrial glandular and stromal breakdown (EGBD) cases in liquid-based cytologic (LBC) preparations of endometrial brushings. The material consists of cytologic smears of 20 cases of proliferative endometrium (PE), 20 cases of EGBD, and 20 cases of endometrioid adenocarcinoma grade 1 (G1) for which histopathological diagnosis was obtained by endometrial curettage. Nuclear findings were examined in PE cells, EGBD-stromal cells, EGBD-metaplastic cells, and G1 cells, respectively. It was examined about the following items: (1) Nuclear shape; (2) A long/minor axis ratio in cell nuclei; (3) An area of cell nuclei; (4) Overlapping nuclei; (5) The distribution pattern of nuclei within cell clusters. The following observations were made: (1) In PE cells, round-oval nuclei appeared to predominate, overlapping nuclei were not observed, and a slightly abnormal distribution pattern of nuclei was recorded; (2) In EGBD-stromal cells, reniform nuclei were characteristically observed, nuclei had small size and a generally elongated appearance, overlapping nuclei were recognized, and a remarkable abnormal distribution pattern of nuclei was found; (3) In EGBD-metaplastic cells, spindle nuclei were a characteristic feature, nuclei were larger in size and had a bipolar appearance, overlapping nuclei with moderately abnormal distribution pattern of nuclei were identified; (4) In G1 cells round-oval nuclei predominated, overlapping nuclei with moderately abnormal distribution pattern of nuclei were found. The study demonstrates that the analysis of selected nuclear findings appears to be very useful in the cytopathological assessment of endometrial lesions in LBC samples, especially for the discrimination of EGBD and G1., (Copyright © 2012 Wiley Periodicals, Inc.)

This study was undertaken to clarify the origin of the chromophilic substance that stained in light green [light green body (LGB)] was observed in the condensed cluster of stromal cells and in the background of endometrial glandular and stromal breakdown cases. The material consists of cytologic smears of endometrial glandular and stromal breakdown (EGBD) from 58 samples in which a histopathological diagnosis was subsequently obtained by endometrial curettage. The following parameters were examined. (1) The occurrence and number of a LGB. As for the "condensed cluster of stromal cells," "condensed cluster of stromal cells including LGB" and "LBG in background," it was observed with all fields on one slide per case. When it was observed more than one in a preparation, the occurrence was determined and the number was also calculated. (2) Immunostaining of paraffin-embedded tissue sections and cytologic preparations. 1 The occurrence of "condensed cluster of stromal cells," "condensed cluster of stromal cells including LGB" and "LGB in background" was 100%, 44.8% and 91.4%, respectively. The number of "condensed cluster of stromal cells," "condensed cluster of stromal cells including LGB" and "LGB in background" was 21.2, 2.0 and 4.0, respectively. 2 When histological sections from paraffin-embedded tissue were tested by immunocytochemistry, "LGB" stained weakly or negative for fibrinogen, whereas it stained positively for CD31 and factor VIII. In addition, it stained positively for CD42b. 3 When cytologic preparation was tested by immunocytochemistry, "LGB" stained positively for CD31, factor VIII and CD42b. However, as for the fibrinogen, quantitative and qualitative evaluation of the immunocytochemical stain was not feasible due to extensive nonspecific reaction in the whole preparation. The "LGB" in EGBD cases proved to be a thrombus mostly made up by platelets, and it seemed that the recognition of the LGB showed to be a useful cytomorphological criterion for an always more accurate diagnosis of EGBD cases., (Copyright © 2010 Wiley Periodicals, Inc.)

Objective: To evaluate the sensitivity and specificity of endometrial cytology obtained by intrauterine sample using a descriptive reporting format for endometrial cytological diagnosis., Study Design: 10,152 consecutive endometrial scrapings obtained in 13 different Japanese hospitals were analyzed. Cytological results were classified as 'negative for malignancy', 'atypical endometrial cells' (ATEC), 'endometrial hyperplasia', 'atypical endometrial hyperplasia' or 'malignant tumor'. ATEC was subclassified as 'ATEC, of undetermined significance' (ATEC-US) and 'ATEC, cannot exclude atypical endometrial hyperplasia or more' (ATEC-A). Cytological results were compared with the histological diagnosis as a gold standard. When the cytological result was 'negative for malignancy' and there was no subsequent histological examination, the case was considered a true negative when the endometrium was assessed as normal on transvaginal ultrasonography and there was no abnormal uterine bleeding., Results: 1,083 cases in which histology was not performed, 557 cases of 'unsatisfactory specimen' and 76 cases of ATEC-US were excluded. In the remaining 8,436 cases, the sensitivity and specificity, positive predictive value and negative predictive value for detecting atypical endometrial hyperplasia or malignant tumors were 79.0 and 99.7, 92.9 and 98.9%, respectively., Conclusion: The current diagnostic standards for endometrial cytology in Japan were established. Specificity is satisfactory for excluding cancer or precancerous diseases., (Copyright © 2012 S. Karger AG, Basel.)

The aim of this study was undertaken to clarify the cytological characteristic of the "condensed clusters of stromal cells," which may be recognized in endometrial glandular and stromal breakdown (EGBD) cases. The material consists of 60 cases of cytologic smears for which histopathological diagnosis was obtained by endometrial curettage; they comprised 30 cases of EGBD and 30 cases of endometrioid adenocarcinoma grade 1 (G1). The following parameters were examined for "condensed clusters of stromal cells" in EGBD and for "clumps of cancer cells" in G1, respectively: (1) the occurrence of "condensed clusters of stromal cells"; (2) the nuclear shape; (3) a longer/shorter axis ratio in cell nuclei; (4) the area of cell nuclei; (5) the presence of overlapping nuclei; (6) nuclear crowding; (7) immunostaining. (1)"Condensed clusters of stromal cells" were only observed in EGBD. (2) A reniform nuclear shape was observed in 100% EGBD (P < 0.0001) in comparison to G1 (3%). (3) The longer/shorter axis ratio in cell nuclei, G1 (1.37 +/- 0.2) was significantly lower in comparison to EGBD (1.53 +/- 0.12, P = 0.0005). (4) Nuclear area in G1 (51.6 +/- 11.9, P < 0.0001) was significantly higher in comparison to EGBD (24.3 +/- 3.9 microm(2)). (5) The score of overlapping nuclei in EGBD (2.5 +/- 0.49) was significantly higher in comparison to G1 (1.8 +/- 0.44, P < 0.0001). (6) The nuclear crowding score was the same both in EGBD (2) and G1 (2) and these findings were not statistically significant. (7) Both CD10 and Wilms' tumor protein 1 were positive in the "condensed clusters of stromal cells" in the EGBD. The anti-cytokeratin staining was positive in "clumps of cancer cells" in the G1. The evaluation of the immunocytochemical findings by combining the Wilms' tumor 1 protein, CD10, and the anti-cytokeratin with the considered cytomorphologic features (reniform nucleus) may be useful for a correct diagnosis of EGBD in endometrial cytology.

Background: For the current report, the authors examined the characteristic features of morphology and molecular biology of phosphatase and tensin homolog (PTEN), beta-catenin, and p53 immunocytochemistry in endometrial carcinoma by using thin-layer cytologic preparations., Methods: During a 6-month period, 120 endometrial samples were collected directly by using the Uterobrush, and thin-layer specimens were prepared. Immunocytochemical expression levels of PTEN, beta-catenin, and p53 were investigated by using 40 specimens of endometrial carcinoma (EC), and 30 specimens each of proliferative endometrium, secretory endometrium, and atrophic endometrium., Results: For PTEN immunoreactivity, the a cutoff value of 50% PTEN expression appeared to be useful for the correct diagnosis of EC in endometrial cytology. For beta-catenin immunoreactivity, an increase in cytoplasmic and nuclear beta-catenin expression and a loss of beta-catenin expression appeared to be useful for the correct diagnosis of EC in endometrial cytology and may aid in the stratification of EC into low grade and high grade EC. For p53 immunoreactivity, the application of a cutoff score >or=4 for nuclear p53 expression appeared to be useful for the diagnosis of high-grade EC in endometrial cytology., Conclusions: Immunocytochemical findings from a combination of PTEN, beta-catenin, and p53, in addition to cytomorphologic features, appeared to be useful for the more accurate diagnosis of EC in endometrial cytology., ((c) 2008 American Cancer Society.)

This article focuses on the characteristic features of morphology and molecular biology of PTEN, beta-catenin, and p53 immunocytochemistry in normal endometrium (proliferative, secretory, and atrophic) and endometrial glandular and stromal breakdown (EGBD) using thin-layer specimens. During a 6-month period, 120 endometrial samples were collected directly using the Uterobrush and a thin-layer specimen was prepared. Immunocytochemical expression of PTEN, beta-catenin, and p53 were investigated using 30 cases each of proliferative endometrium (PE), secretory endometrium (SE), atrophic endometrium (AE), and EGBD.PTEN expression of normal endometrial glandular epithelial cells changes with the hormonal status; PE produce very high expression, SE creates attenuation or disappearance of PTEN expression and AE diminished more in comparison with SE. PTEN expression of EGBD showed a tendency towards attenuation compared with PE, but showed high expression in comparison with SE and AE. As for the immunoreactivity of beta-catenin, in all phases (PE, SE, AE, and EGBD), it was observed in the cytoplasm of glandular epithelial cells, but not nuclei, and showed strong membranous staining. As for the p53 immunoreactivity, p53 positivity was not observed in the glandular epithelial cells in all phases (PE, SE, AE, and EGBD) with the exception of some metaplastic cells. The presence of p53 immunoreactivity of a weak, low ratio in metaplastic cells was unexpected. In the current study, the expression manner of PTEN, beta-catenin, and p53 immunocytochemistry was observed in the normal endometrium (PE, SE, and AE) and EGBD., ((c) 2008 Wiley-Liss, Inc.)

The purpose of the current study was to examine the use of thin-layer cytologic (TLC) preparation compared to conventional cytologic preparation (CCP) in the normal endometrium (proliferative, secretory, atrophic) and endometrial glandular and stromal breakdown (EGBD). During a 6-month period, we compiled 158 cases by collecting a direct endometrial sample using the Uterobrush. The material comprised 40 cases of proliferative endometrium, 42 cases of secretory endometrium, 46 cases of atrophic endometrium, and 30 cases of EGBD. The following points were investigated: (1) number of endometrial epithelial cell clumps; (2) presence of TLC > CCP cases on number of epithelial cell clumps; (3) number of condensed cluster of stromal cells; (4) presence of TLC > CCP cases on number of condensed cluster of stromal cells; (5) presence of metaplastic clumps with irregular protrusion-containing condensed stromal cluster; (6) presence of a clear background; (7) presence of blood vessel in TLC; (8) presence of blood vessel of length more than diameter of a field in object x20 glasses in TLC. (1) In all phases, the number of epithelial cell clumps per a unit area of a preparation of TLC is greater than in CCP. (2) Cells (condensed cluster of stromal cells and metaplastic clumps with irregular protrusion-containing condensed stromal cluster) of useful and adequate numbers for a diagnosis of EGBD were observed in TLC. (3) In all phases, TLC was significantly higher than CCP on the appearance of a clear background. (4) The proliferative endometrium and secretory endometrium were highly significant in comparison with atrophic endometrium and EGBD, respectively, in terms of the occurrence of a blood vessel of length more than diameter of a field in object x20 glasses. Although the preparation area of TLC is smaller than that of CCP, the preparation has a clean background so that an accurate report on the patient's condition is possible. Therefore, TLC preparation is a useful tool for the accurate and reliable diagnosis of normal endometrial phase and EGBD, because the preparation area is confined and identification of the target cell clumps is easy.

Background: To evaluate the efficacy and toxicity of the combination of mitomycin C, etoposide, cisplatin, and epirubicin (MEPA) as neoadjuvant therapy for patients with cervical adenocarcinoma., Methods: Fourteen patients with cervical adenocarcinoma received neoadjuvant MEPA therapy followed by radical hysterectomy. The International Federation of Gynecology and Obstetrics stage was: IB1 in 2 patients, IB2 in 5, and IIB in 7. The MEPA regimen consisted of mitomycin C (15 mg/m2) on day 1, etoposide (70 mg/m2) on days 1 to 3, cisplatin (15 mg/m2) on days 1 to 5, and epirubicin (30 mg/m2) on day 1, with this course being repeated every 4 weeks. After two or three courses of chemotherapy, all patients underwent radical hysterectomy. Postoperative radiotherapy was given to 6 patients who showed risk factors at surgery., Results: Of the 14 patients, 7 had complete remission (CR) clinically, 6 had partial remission, and only 1 showed no change. Examination of surgical material revealed no residual disease in 6 patients, and microscopic residual disease (<5 mm) in 2 patients. The patients who had no residual disease or microscopic disease in their hysterectomy specimens showed a significantly longer survival than those with macroscopic residual disease (P = 0.012). The dose-limiting toxicity was myelosuppression. Of the 33 treatment cycles administered, leukopenia of grade 3 or more occurred in 70%,and thrombocytopenia of grade 3 or more occurred in 79%. There were no therapy-related deaths., Conclusion: Although severe myelosuppression was also observed, there was a satisfactory response rate to MEPA therapy, which showed a good pathological CR rate.

Objective: To identify a high-risk subgroup among patients with cytology-positive stage IIIA endometrial cancer., Study Design: Fifty-four stage IIIA endometrial cancer patients who were positive only on peritoneal cytology were divided into two groups based on the cytologic pattern of their peritoneal smears. In group A, malignant cell clusters had well-defined edges, while the tumor cell clusters had scalloped edges in group B. The prognostic significance of these findings was investigated., Results: The five-year disease-free survival rate was 97.5% in group A (n=40) versus 50% in group B (n = 14). Multivariate analysis confirmed that the cytologic pattern had an independent influence on survival., Conclusion: Positive peritoneal cytology composed of malignant cell clusters with well-defined edges has no impact on survival. Only endometrial cancer patients who show tumor cell clusters with scalloped edges in peritoneal smears are worth considering for upstaging.

Background and Objectives: To determine the prognostic significance of the colposcopic tumor size in the management of cervical cancer., Methods: Clinicopathological analysis was performed in 751 consecutive patients with stage IB squamous cervical cancer who were surgically treated in a single institute. The colposcopic tumor size was measured postoperatively on surgical specimens. Univariate and multivariate analyses were performed to determine the prognostic significance of various pathological factors., Results: Among the pathological factors examined, lymph node metastasis, parametrial extension, deep stromal invasion, vessel permeation, endometrial extension, and colposcopic tumor size were found to be prognostic factors in univariate analysis, whereas multivariate analysis has confirmed that only three factors, i.e., lymph node metastasis, parametrial involvement, and colposcopic tumor size were independently associated with the disease-free interval., Conclusions: These results indicate that the colposcopic tumor size is an independent prognostic factor in squamous cervical cancer and can be used as an indicator of treatment options.

The authors evaluated the hemostatic abnormalities occurring in the postoperative period of eight patients with malignant tumors and compared them with those occurring in the postoperative period of eight patients with benign tumors. Two of the patients with malignant tumor presented pulmonary embolism after operation. Plasma fibrinogen and fibrin degradation product levels in patients with malignant tumors were already high before operation and further increased significantly after operation. The plasma levels of D-dimer, thrombin-antithrombin complex, and free-tissue factor pathway inhibitor were increased in both groups after operation, but they were higher in patients with malignant tumors than in patients with benign tumors. The plasma levels of protein C and antithrombin were significantly decreased in both groups after operation. but they were significantly lower in patients with malignant tumors than in those with benign tumors. The decreased activity of protein C or antithrombin may be not only a risk factor of thrombotic disease, such as pulmonary embolism, but also the cause of thrombosis. In patients with malignant tumors, the operation time was significantly longer than that in patients with benign tumors. This long operative period might cause vascular endothelial cell injury which is reflected by the plasma levels of free-tissue factor pathway inhibitor, antithrombin, and protein C.

Objective: To investigate the relationship between the morphologic features of endometrial adenocarcinoma cells in peritoneal fluids (effusions and washings) and macroscopic intraabdominal adenocarcinoma at laparotomy as well as prognosis., Study Design: Seventy-one patients with endometrial adenocarcinoma who showed positive peritoneal cytology at laparotomy were clinically divided into three groups: 25 patients with macroscopic neoplastic seeding in the peritoneal cavity (type 1), 38 patients without macroscopic peritoneal metastasis who survived with no evidence of disease (type 2) and 8 patients without macroscopic peritoneal metastasis who later developed recurrence of adenocarcinoma (type 3). Morphologic features of the adenocarcinoma cells in smears of peritoneal fluids were examined., Results: Most of the smears from type 1 patients showed moderate to high cellularity, scalloped edges of cell clusters and isolated adenocarcinoma cells, whereas these features were seldom observed in type 2 patients. Although not all type 3 patients demonstrated these three features, patients in the series whose specimens exhibited none of the three features did not show any peritoneal lesions or have a recurrence of their disease., Conclusion: The finding of endometrial adenocarcinoma cells exhibiting high cellularity, scalloped edge of cell clusters and isolated cells in smears of peritoneal fluid is associated with the presence of intraabdominal macroscopic metastatic lesions and could be regarded as a risk factor for intraabdominal recurrence of carcinoma.

Objective: The aim of this study was to investigate the value of the International Federation of Obstetrics and Gynecology (FIGO) classification (1995) for early invasive cervical cancer. Methods. Clinico-pathological analysis was performed in 402 patients with invasive squamous cervical cancer in whom the depth of stromal invasion was 5 mm or less., Results: The incidence of lymph node metastasis was 1.2% (1/82) in patients with 3 mm or less depth of invasion; the node-positive patient was in stage IA1. The incidence of lymph node metastasis was 6.8% (5/73) in patients with 3-5 mm depth of invasion; this increased with increasing horizontal spread from 3.4% for 7 mm or less to 9.1% for more than 7 mm. None of the patients in this series had metastasis to the parametrial tissues. Of 4 patients with recurrence, 3 had horizontal spread of more than 7 mm and the remaining patient was in stage IA2., Conclusion: The FIGO definition of early squamous cervical cancer is generally acceptable in its present form., (Copyright 1999 Academic Press.)