Successful Surveillance Using Endometrial Cytology in a Woman With Lynch Syndrome.

Lynch syndrome (LS) results from pathogenic variants in mismatch repair genes and is the most common hereditary cancer syndrome. Some guidelines or studies recommend restricting screening according to endometrial cancer (EC) using endometrial biopsy. The pooled sensitivity and specificity of endometrial cytology for detecting endometrial atypical hyperplasia or cancer have been reported to be as high as the pooled sensitivity and specificity of endometrial biopsy. We conduct transvaginal ultrasound and endometrial cytology in women with LS every six months as surveillance for gynecological malignancy. Through this surveillance program, we can detect early-stage EC in women with LS. Here, we report the case of a patient with stage IA EC detected by endometrial cytology and treated completely. The patient was a 47-year-old woman under surveillance for gynecological malignancy. She was diagnosed as having LS with a germline pathogenic variant in MSH6 after surgery for rectal cancer. Thereafter, gynecological surveillance was started. She had regular menstruation and never experienced atypical genital bleeding. However, her cytopathological findings indicated grade 1 endometrial carcinoma. Endometrial biopsy was performed and endometrial carcinoma was confirmed pathologically. A laparoscopic modified radical hysterectomy with bilateral salpingo-oophorectomy was performed. The resected specimen was reviewed pathologically, and the tumor was finally diagnosed as grade 1 endometrioid carcinoma confined to the endometrium without lymphovascular space invasion. She has remained asymptomatic and free of cancer for five years without any adjuvant therapy. We achieved successful surveillance using endometrial cytology. Endometrial cytology could replace endometrial biopsy as a screening tool for EC.

Endometrial cytological findings for a mesonephric-like endometrial adenocarcinoma: A case report.

A mesonephric-like endometrial adenocarcinoma (ML-EAC) is very rare and has a worse prognosis than other endometrial carcinomas. We describe an ML-EAC and report our endometrial cytological findings. A 76-year-old woman presented with irregular genital bleeding and a uterine mass. Endometrial cytology revealed atypical cylindrical or spindle-shaped cells in the form of small aggregates or solitary cells. The cell aggregates exhibited irregularly stacked papillary structures, small glandular structures, and fenestrated structures. The atypical cells had a nucleus with fine-granular chromatin and a granular cytoplasm, and nuclear grooves and intranuclear pseudo-inclusions were present. Hyaline globules were observed in the glandular lumens and in the background. The presumptive histological type was an adenocarcinoma, but the cytological features were different from those of an endometrioid carcinoma. A histological examination of the endometrial biopsy revealed an adenocarcinoma, and a simple hysterectomy was performed. A grayish-white elevated mass measuring 90 mm × 70 mm × 40 mm was observed on the uterine corpus in the hysterectomy specimen. Histologically, the tumor proliferated as complex tubular structures containing eosinophilic colloid-like materials and trabecular structures. The tumor cells were diffuse and positive for GATA-3 and partially positive for thyroid transcription factor-1. Estrogen and progesterone receptors were negative. An ML-EAC was diagnosed. The tumor was invasive and extended beyond one-half of the muscle layer with a high degree of vascular invasion. In conclusion, we need to focus on the various shapes of the cell aggregate, nuclear grooves, and intranuclear pseudo-inclusions of tumor cells to distinguish an ML-EAC from other endometrial carcinomas in endometrial cytology.

A review of the directly sampled endometrial cytology on LBC samples: Classification, microscopic criteria and beyond.

The Yokohama System for Reporting Endometrial Cytology (TYS) has been proposed by an expert meeting under the auspices of the International Academy of Cytology (IAC) in May 2016 at the IAC in Yokohama. Since its introduction, the TYS has been receiving worldwide acceptance, and this review aims to assess its global impact. 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 re-evaluate the role of endometrial cytology. LBC is a useful tool in the cytologic diagnosis and follow-up of endometrial abnormalities, which remains complementary to the emerging molecular diagnostic cytopathology. The study of LBC 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. In conclusion, our review of the published data suggests that the TYS is a valid classification scheme that has been widely accepted by cytopathologists globally, is highly reproducible and makes a valuable contribution to clinical therapeutic management. At present, molecular cytopathology is a rapidly evolving field of modern cytopathology, which underlines the effective interplay between genomics and cytology. This review aims to provide a comprehensive review of the drawbacks of endometrial cytopathology, particularly in terms of endometrial cancer diagnosis and molecular testing.

A study evaluating liquid-based endometrial cytology test and transvaginal ultrasonography as a screening tool for endometrial cancer in 570 postmenopausal women.

OBJECTIVE: To evaluate the combination of transvaginal ultrasonography (TVS) and endometrial cytology test (ECT) as a potential diagnostic strategy for endometrial cancer and endometrial precancerous lesions in postmenopausal patients. METHODS: 570 postmenopausal patients admitted in our hospital due to abnormal bleeding or other symptoms and/or with endometrium thickness over 5 mm on ultrasound. The endometrial thickness was evaluated by TVS. Following obtainment with written consent, all patients underwent ECT, hysteroscopy and then dilatation and curettage (D&C). Cytological sampling was conducted by scratching the uterus cavity using SAP-1 and the samples were prepared as liquid-based smear using SurePath technology. The samples were stained using Papanicolaou method. The correlation between cytological diagnosis and TVS results with the D&C histological diagnosis was analyzed. The WHO classification was used for diagnosis. RESULTS: Sensitivity of ECT, TVS, ECT or TVS positive, ECT and TVS positive to diagnose atypical hyperplasia or worse were estimated at 80.7%, 86.8%, 97.4%, 70.2%, specificity at 94.7%, 20.4%, 17.5%, 88.4%, positive predictive value at 58.2%, 21.1%, 22.8%, 60.2%, negative predictive value at 94.4%, 86.1%, 96.4%, 92.2%, and accuracy at 84.6%, 33.7%, 33.5%, 84.7%, respectively. CONCLUSIONS: Transvaginal ultrasonography and Endometrial cytology test may be regarded as a effective first-line method in endometrial pathology detection in postmenopausal women.

Screening of Endometrial Cancer Related to Lynch Syndrome in China by Suction Curettage-Based Cytology and Histology: A Retrospective Study.

Objective: To explore the feasibility of sampling Chinese patients by suction curettage for cytological and histological screening of endometrial cancer related to Lynch syndrome. Methods: This retrospective study enrolled patients who underwent endometrial biopsy at our hospital between May 2018 and January 2019. Endometrial sampling (cytological and micro-histological specimens) was conducted by suction curettage. The gold standard for diagnosis was traditional sharp dilation and curettage (D&C). The sensitivity, specificity, and diagnostic accuracy of cytology, micro-histology, and the combination of cytology and micro-histology were calculated. Additionally, receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficiency of three screening methods. Mismatch repair proteins were further detected using immunohistochemistry (IHC) in endometrial cancer. Results: This retrospective finally enrolled 100 patients, which satisfactory samples were obtained from 96 patients for liquid-based cytology and 93 patients for microtissue histology. The concordance rates with D&C, sensitivity, and specificity were 94.8%, 76.9%, and 97.5% for liquid-based cytology, 96.8%, 84.6%, and 98.8% for microtissue histology, and 99.0%, 92.3%, and 100.0% for liquid-based cytology and microtissue histology combined, respectively. The AUC of ROC curves in liquid-based cytology, microtissue histology, and the combined methods for diagnostic ability were 0.873, 0.917, and 0.962, respectively. Absence rates of MLHl, MSH2, MSH6, and PMS2 proteins were 15.3% (2/13), 0% (0/13), 7.7% (1/13), and 15.3% (2/13) in the 13 endometrial cancer samples. Conclusion: Liquid-based cytology and microtissue histology samples from suction curettage combined IHC are useful for endometrial cancer screening.

Positive Rate of Malignant Cells in Endometrial Cytology Samples of Ovarian Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer Patients: A Systematic Review and Meta-Analysis.

To estimate the feasibility of diagnosing ovarian cancer, fallopian tube cancer, and primary peritoneal cancer through endometrial cytology, we performed a systematic review and meta-analysis to calculate the pooled positive rate of malignant cells in endometrial cytology samples. We queried PubMed, EMBASE, Medline, and Cochrane Central Register of Controlled Trails from inception to November 12, 2020 for studies estimating positive rates of malignant cells in endometrial cytology samples from patients with ovarian cancer, fallopian tube cancer, and primary peritoneal cancer. The positive rates of the included studies were calculated as pooled positive rate through meta-analyses of proportion. Subgroup analysis based on different sampling methods was conducted. Seven retrospective studies involving 975 patients were included. Pooled positive rate of malignant cells in endometrial cytology specimens of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer patients was 23% (95% CI: 16% - 34%). Statistical heterogeneity between the included studies was considerable (I2 = 89%, P < 0.01). The pooled positive rates of the group of brushes and the group of aspiration smears were 13% (95% CI: 10% - 17%, I2 = 0, P = 0.45) and 33% (95% CI: 25% - 42%, I2 = 80%, P < 0.01), respectively. Although endometrial cytology is not an ideal diagnostic tool for ovarian cancer, fallopian tube cancer, and primary peritoneal cancer, it is a convenient, painless, and easy-to-implement adjunct to other tools. Sampling method is one of the factors that affect the detection rate.

Endometrial Cytology in Diagnosis of Endometrial Cancer: A Systematic Review and Meta-Analysis of Diagnostic Accuracy.

BACKGROUND: Because the incidence of endometrial cancer has been increasing every year, it is important to identify an effective screening method for it. The endometrial cytology test (ECT) is considered to be the more acceptable technique compared to invasive endometrial sampling. METHODS: The study followed the Priority Reporting Project for Systematic Evaluation and Meta-Analysis (PRISMA-DTA) protocol. This systematic rating searched EMBASE and Web of Science databases for studies on ECT for endometrial cancer from the databases' dates of inception to 30 September 2022. All literature screening and data extraction were performed by two researchers, while the methodological quality of the included studies was assessed against defined inclusion criteria. And a third researcher resolves the disagreements. RESULTS: Twenty-six studies were eventually included in this final analysis. Meta-analysis results showed that the diagnostic accuracy characteristics of ECT for endometrial cancer were as follows: combined sensitivity = 0.84 [95% confidence interval (CI) (0.83-0.86)], combined specificity = 0.98 [95% CI (0.98-0.98)], combined positive likelihood ratio = 34.65 [95% CI (20.90-57.45)], combined negative likelihood ratio = 0.21 [95% CI (0.15-0.30)], and area under the summary receiver operating characteristic curve = 0.9673. CONCLUSIONS: ECT had the ability to detect endometrial cancer with strong specificity, although some studies have demonstrated significant differences in sensitivity.

Cytopathological features associated with POLE mutation in endometrial cancer.

OBJECTIVE: For patients with endometrial cancer, the POLE (polymerase epsilon) mutation (POLEmut)-subtype, one of four molecular-analysis-based categories in the Cancer Genome Atlas (TCGA), has the best prognosis. The following histological characteristics are typically observed in endometroid carcinoma cases with the POLEmut-subtype: (1) the presence of tumour giant cells, (2) numerous tumour-infiltrating lymphocytes (TILs) and/or peri-tumoral lymphocytes, and (3) a high grade. However, in the context of cytology, the morphological characteristics of this subtype remain unknown. METHODS: DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues was subjected to next-generation sequencing analysis and categorised according to the TCGA classifications. Genomic mutation, tumour mutation burden (TMB), and microsatellite instability were also assessed. Cytological specimens of resected uteri obtained using the Papanicolaou method were histologically separated into three types. RESULTS: Seven out of 112 patients (6%) with endometrial cancer were diagnosed with the POLEmut-subtype between January 2019 and August 2021. Tumour giant cells were observed in three cases (43%) on histology and cytology. TIL and/or peritumoral lymphocytes with inflammatory cells were detected in five cases (71%) on histology and three cases (43%) on cytology. Cases in which these three characteristics were observed on both cytology and histology may have belonged to the POLEmut-subtype. There were no cases in which these characteristics were absent on histology but present on cytology. TMB tended to be higher in cases when the three characteristics were observed in both cytological and histological findings. CONCLUSIONS: Preoperative endometrial cytology highlighted the characteristics of the POLEmut-subtype in the histological analysis of resected uterine specimens and has the potential to play an important role in treatment decisions.

Comparison Between Gynecological Examination Methods and Sample Collection Techniques for the Diagnosis of Endometritis in Subfertile Mares.

Endometritis is a relevant cause of subfertility in mares. However, the accurate diagnosis, essential for effective treatment, can be difficult due to the variability of results and interpretations resulting from different examination methods and sample collection techniques. The present work compared gynecological evaluation methods and sample collection techniques to diagnose endometritis in subfertile mares. Forty animals with a history of subfertility were selected for gynecological evaluation using clinical methodologies, such as perineal conformation, transrectal palpation and ultrasonography, vaginoscopy, and digital examination of the cervix. In addition, we performed laboratory analyses, including uterine microbiological culture and endometrial cytology and histology, of which the latter is the gold standard for the diagnosis of endometritis. Samples were collected for microbiological culture and endometrial cytological evaluations using three different techniques: a commercial cytobrush/swab collector, low-volume uterine flush, and a new tested technique, by flush the fragment resulting from the endometrial biopsy. Transrectal palpation and ultrasound showed the best results among clinical examinations. However, they were less efficient in laboratory tests of endometrial cytology and uterine microbiological culture, in which the latter showed the highest sensitivity and specificity for endometritis compared with endometrial histology. The use of multiple results from different methods has also proved to be an effective alternative for diagnosis. Among the techniques used to collect endometrial material for cytology and microbiological culture, the most effective and practical in this study was the commercial cytobrush/swab collector.

Morphometrical Differences among Endometrial Endometrioid Carcinoma Grade 1, Grade 3, and Serous Carcinoma in Endometrial Liquid-Based Cytology Preparations.

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

Brief Research Report: Expression of PD-1 and CTLA-4 in T Lymphocytes and Their Relationship With the Periparturient Period and the Endometrial Cytology of Dairy Cows During the Postpartum Period.

The present study sought to evaluate the expression of PD-1 and CTLA-4 in blood T lymphocytes during the periparturient period and their relationship with uterine health in dairy cows, as determined by endometrial cytology and serum concentrations of ß-hydroxybutyrate (BHB) and non-esterified fatty acids (NEFAs), which are indicators of a negative energy balance. The second objective of this study was to investigate whether the expression of PD-1 and CTLA-4 in T lymphocytes is associated with the serum acute phase-protein haptoglobin concentration during the periparturient period. To address these objectives, 26 clinically healthy dairy cows were used. Peripheral blood was collected 14 days prepartum (T-14), at calving (T0), and 30 days postpartum (T30) to measure the expression of PD-1 and CTLA-4 in blood T lymphocytes by flow cytometry. In addition, we collected blood at T0, 10 days after parturition (T10), and T30 to obtain serum and determine the serum concentrations of NEFA, BHB, and Hp. Endometrial cytology was performed at T10, 20 days after parturition (T20), and T30. In the present study, we observed higher expression of CTLA-4 and PD-1 in T lymphocytes at parturition and in the prepartum period, which could indicate a relationship between these immune checkpoints and immunological tolerance during gestation in dairy cattle. In addition, a negative association between the expression of these immune checkpoints prepartum or at parturition and endometrial cytology at T20 and T30 was observed, indicating the negative implications of these immune response regulators in susceptibility to infections. This finding was further corroborated by the relationship between the serum concentration of haptoglobin and the expression of CTLA-4 and PD-1 by T lymphocytes. However, we did not observe a relationship between the indicators of negative energy balance, evaluated by the serum concentrations of BHB and NEFA, and the expression of the immune checkpoint markers studied. Thus, our findings represent an initial step that paves the way for the development of new therapeutic alternatives directed by the host with the objective of increasing the resistance of dairy cattle to infections in this critical period of life.

Uterine Tumor Resembling Ovarian Sex Cord Tumor: A Case Report.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are extremely rare, occurring in less than 1% of uterine stromal tumors, and they are considered to have a low malignant potential. Due to the small number of cases, no standard treatment has been defined. A 77-year-old woman with postmenopausal bleeding was admitted to our department. Imaging studies revealed a substantial mass around 30 mm in size on the anterior uterine wall. A total hysterectomy and bilateral salpingo-oophorectomy were performed for further diagnosis and treatment. The tumor revealed histopathological findings of a sex cord-like growth pattern in the form of fascicles, cords, or small nests. Immunohistochemical findings revealed that the tumor cells were positively reactive to alpha-SMA, calretinin, CD99, estrogen receptor, and progesterone receptor, collectively diagnosed as UTROSCT. No recurrence was observed over 12 months after treatment. We experienced the treatment of UTROSCT, an extremely rare tumor that occurs in elderly women. Although most cases of UTROSCT have a benign clinical course, several cases of recurrence and metastasis have been reported. It should be followed up for a long term after treatment.

Hypermethylated CDO1 and ZNF454 in Cytological Specimens as Screening Biomarkers for Endometrial Cancer.

We aimed to estimate the diagnostic value of DNA methylation levels in cytological samples of endometrial cancer (EC) and atypical hyperplasia (AH). Two hypermethylated genes, namely, cysteine dioxygenase type 1 (CDO1) and zinc finger protein 454 (ZNF454), in patients with EC were identified from The Cancer Genome Atlas database. In 103 endometrial histological specimens (the training set), the methylation levels of candidate genes were verified by quantitative methylation-specific polymerase chain reaction (qMSP). The methylation levels of another 120 cytological specimens (the testing set) were evaluated. Sensitivity (Se), specificity (Sp), accuracy, and area under the curve (AUC) were determined, with diagnosis verified by histopathological results. CDO1 and ZNF454 verified hypermethylation in histological specimens of patients with EC and AH compared with those with benign and normal endometrium (P < 0.001). In cytological specimens, hypermethylated CDO1 showed 86.36% Se and 90.79% Sp with the cutoff value of 6.0 to distinguish between malignant and benign groups; ZNF454 showed 79.55% Se and 93.42% Sp with the cutoff value of 7.1. When the two genes were combined, Se increased to 90.91% and Sp was 86.84%. AUC reached 0.931 (95% CI: 0.885-0.976). The diagnostic accuracy with cytology had no significant difference with endometrial tissue (P = 0.847 for CDO1, P = 0.108 for ZNF454, and P = 0.665 for their combination). Hypermethylated CDO1 and ZNF454 in endometrial cytology showed high Se, Sp, and AUC to detect EC and AH. Methylation analysis of endometrial cytology is promising biomarker for the screening of EC and AH.

Effect of calving to timed artificial insemination interval on fertility of beef cows.

The objectives of this study were to determine the effect of calving to timed artificial insemination (C-TAI) interval on fertility of Bos taurus and Bos indicus cows and to determine the best C-TAI interval to include postpartum cows in TAI programs in each genotype (B. taurus and B. indicus). In experiment 1, a retrospective study was performed, with data from 2,709 TAI in Bos taurus and Bos indicus cows with different C-TAI intervals. There was a positive linear effect of C-TAI interval on the pregnancy probability (p < .0001). However, there was no effect or interaction with the genotype. When C-TAI intervals were grouped in classes, pregnancy rate differed in groups (p < .05). Receiver operating characteristic (ROC) analysis was performed, and it was observed that 52 days would be the better C-TAI interval to maximize fertility in beef cows. According to the previous result, we further stratified into two C-TAI interval groups (≤ 52 days or > 52 days). Cows with C-TAI longer than 52 days (C-TAI > 52) had greater pregnancy rate (56%) than cows with short C-TAI (46%; p < .01). In experiment 2, 18 postpartum beef cows were subjected to TAI protocol at different C-TAI intervals (n = 6 cows per group): 40, 60 or 80 days postpartum. Cows with 60 days of C-TAI had a greater preovulatory follicle diameter than cows with 80 days postpartum (p < .05). The C-TAI interval did not affect (p > .05) the ovulation rate nor the proportion of endometrial polymorphonuclear leucocytes. We conclude that C-TAI interval affects pregnancy rate in both Bos taurus and Bos indicus. We recommend a C-TAI interval longer than 52 days to increase fertility of beef cows included in TAI programs.

The effect of subclinical endometritis on reproductive performance in postpartum Bos indicus multiparous beef cows.

The objective was to investigate the prevalence of subclinical endometritis (SE) in postpartum Bos indicus multiparous beef cows using different polymorphonuclear cells (PMN) threshold ratios, and to evaluate the impacts of SE on their reproductive performance. A total of 689 postpartum Nellore cows (45.2 ± 7.8 days postpartum) were submitted to an estrus synchronization protocol + timed-artificial insemination (TAI). Endometrial cytology samples were collected by cytobrush before the beginning of the protocol. Cows were considered positive for SE if: (PMN) ≥ 3% (PMN3), PMN ≥ 5% (PMN5) and PMN ≥ 7% (PMN7). Pregnancy diagnosis was performed at 30 and 100 d after TAI. The prevalence of cows categorized as positive for SE increased (P < 0.05) as the threshold was lowered (PMN7 = 3.9%; PMN5 = 5.5%; PMN3 = 9.1%). Positive SE cows had similar (P > 0.41) BCS, days postpartum, and expression of estrus at TAI compared with negative SE cows. Positive SE cows had decreased (P = 0.04) pregnancy rates compared to negative SE cows in the PMN5 threshold (26.3 ± 8.7% vs 44.5 ± 4.1%); however, no difference (P > 0.45) was observed between positive and negative SE cows in the PMN3 and PMN7 thresholds. Embryonic mortality between days 30 and 100 was not affected by SE (P > 0.16). In conclusion, the prevalence of SE varies based on the PMN threshold used, whereas SE at the beginning of the TAI protocol decreased the pregnancy rates in postpartum Bos indicus beef cows when the PMN5 was used.

Clinical Usefulness of Endometrial Cytology in Determining the Therapeutic Effect of Fertility Preserving Therapy.

INTRODUCTION: The significance of endometrial cytology in determining the therapeutic efficacy of medroxyprogesterone acetate (MPA) therapy is unclear. This study aimed to evaluate the clinical usefulness of endometrial cytology during MPA therapy. METHODS: Overall, 77 patients who underwent dilatation and curettage (D&C) to evaluate the therapeutic efficacy of MPA therapy at our hospital between January 2018 and December 2019 were retrospectively analyzed. The results of D&C, cytological evaluation, and other clinicopathological factors were analyzed based on the patients' medical records. RESULTS: The sensitivity and specificity of cytology were 61% and 92%, respectively, with D&C being the gold standard for diagnosis in 142 D&C/cytological examinations. Among patients with no residual disease on D&C, 5 (4%) had suspicious or positive cytology. Although MPA therapy was terminated in 3 of these patients, only 1 patient had early recurrence, and the frequency of recurrence was similar to that of patients who showed negative results in both D&C and cytology. DISCUSSION/CONCLUSION: The sensitivity of endometrial cytology in determining the therapeutic effect of MPA therapy is low, and we confirmed that the omission of D&C is unacceptable. Our findings also suggested that the addition of cytological evaluation to D&C during MPA therapy had a low clinical significance.

A study on preserving endometrial glandular architecture during preparation using BD SurePath™ liquid-based cytology reagents: Cellular fixation with preservative fluid requires at least 18 h.

INTRODUCTION: This study aimed to determine the causes of disruption of the three-dimensional architecture of endometrial glands prepared using BD SurePath™ liquid-based cytology (SP-LBC) reagents. One sample preparation method for endometrial cytology is presented in which this three-dimensional architecture can be retained. METHODS: SP-LBC specimens were prepared by the following three methods: (1) using the BD PrepMateTM (PrepMate) System after cellular fixation for 1-6 h (method A); (2) without using the PrepMate System after cellular fixation for 1-6 h (method B); and (3) using the PrepMate System after cellular fixation for at least 18 h (method C). Size and numbers of endometrial cell clusters and numbers of solitary scattered cells were then evaluated. RESULTS: Significantly higher numbers of cell clusters with a major axis of 200 µm or more were yielded by method C (71.3 ± 57.2) than methods A (9.3 ± 5.9, P < 0.001) or B (44.3 ± 28.8, P < 0.05). Method B yielded significantly higher numbers of cell clusters than method A (P < 0.001). Method A (132.2 ± 107.7, p < 0.001) yielded significantly higher numbers of solitary scattered cells than methods B (29.1 ± 14.8) and C (35.7 ± 23.3). No significant difference in solitary cell numbers was found between methods B and C. CONCLUSIONS: Retention of endometrial glandular architecture is rendered possible by allowing sample fixation times of 18 h or more when preparing specimens using the PrepMate System.

Tao brush endometrial cytology is a sensitive diagnostic tool for cancer and hyperplasia among women presenting to clinic with abnormal uterine bleeding.

BACKGROUND: Abnormal uterine bleeding requires the investigation of the endometrium. Histology is typically used but there remains room for the improvement and use of cytology. METHODS: Women presenting for clinically indicated office endometrial biopsy were prospectively enrolled. Tao endometrial brushing and office endometrial biopsy were performed, and surgical procedure if clinically indicated. Tao brush cytology specimens were blindly reviewed by up to three pathologists, consensus obtained, and scored as: benign, atypical (favor benign), suspicious, positive for malignancy, or non-diagnostic. Cytology and histology were compared to surgical pathology to determine sensitivity, specificity, positive, and negative predictive values to detect AH (atypical hyperplasia) or EC (endometrial cancer). RESULTS: Clinical indications of 197 enrolled patients included postmenopausal bleeding (90, 45.7%), abnormal uterine bleeding (94, 47.7%), and abnormal endometrium on ultrasound without bleeding (13, 6.6%). Of the 197 patients, 185 (93.9%) had cytology score consensus and a total of 196 (99.5%) had consensus regarding cytology positivity. Surgical pathology diagnoses (N = 85) were 13 (15.3%) FIGO grade 1 or 2 EC, 3 (3.5%) AH, and 69 (81.2%) benign endometrium. Sensitivity and specificity to detect EC or AH were 93.7% and 100%, respectively, via endometrial biopsy; 87.5% and 63.8%, respectively, via endometrial cytology when scores of malignancy, suspicious, or atypical were considered positive. CONCLUSIONS: In a high-risk population, Tao brush endometrial cytology showed high sensitivity to detect AH and EC comparable to biopsy histology when considering scores of malignancy, suspicious, atypical, and non-diagnostic. Revisiting the potential value of endometrial cytology in the contemporary era of endometrial diagnostic workup is warranted.

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.

Nuclear morphometry as an adjunct to cytopathologic examination of endometrial brushings on LBC samples: A prospective approach to combined evaluation in endometrial neoplasms and look alikes.

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.