Practical usefulness of atypical endometrial cell categories within the new classification of endometrial cytology when applied to conventional smears.

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.

Inter-observer reproducibility of endometrial cytology by the Osaki Study Group method: utilising the Becton Dickinson SurePath™ liquid-based cytology.

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.

Dominant sequences of human major histocompatibility complex conserved extended haplotypes from HLA-DQA2 to DAXX.

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.

Utility of liquid-based cytology in endometrial pathology: diagnosis of endometrial carcinoma.

OBJECTIVE: The purpose of this study was to examine the utility of SurePath-liquid-based cytology (LBC) compared to conventional cytological preparations (CCP) in the identification of endometrial carcinoma. METHODS: During a 13-month period, direct endometrial samples were collected from 120 patients using the Uterobrush. The material comprised 30 cases each of endometrial carcinoma, proliferative endometrium, secretory endometrium and atrophic endometrium. The following points were investigated:(i) the frequency of cell clumps in endometrial carcinoma; (ii) the area of cell nuclei; (iii) overlapping nuclei. RESULTS: (i) Comparison of the frequency of cell clumps with irregular protrusion pattern and papillo-tubular pattern showed no statistically significant difference in either type of cell clump between CCP and LBC. (ii) Comparison of the nuclear area of cells showed a sequential decrease from endometrial carcinoma to secretory endometrium, to proliferative endometrium and to atrophic endometrium, which was significant in CCP and LBC. (iii) Nuclear area was significantly lower with LBC compared with CCP in endometrial carcinoma, secretory endometrium and proliferative endometrium but not atrophic endometrium. (iv) Comparison of the degree of overlapping nuclei showed a sequential decrease from endometrial carcinoma to proliferative endometrium, to secretory endometrium and to atrophic endometrium, which was significant in both CCP and LBC. (v) Comparison of the degree of overlapping nuclei between CCP and LBC showed no significant difference for normal types of endometrium, but LBC had significantly higher values (P < 0.0001) in endometrial carcinoma than in CCP. CONCLUSIONS: The results of this study revealed that applying diagnostic criteria used in CCP to LBC was easy to achieve, because LBC had excellent cytoarchitectural preservation and cells were well presented. Although we have not examined all cytological features of malignancy and have not considered atypical hyperplasia, we believe that this method may be a useful tool in the diagnosis of endometrial cytology.

New diagnostic reporting format for endometrial cytology based on cytoarchitectural criteria.

OBJECTIVE: The aim of this study was to develop a new reporting format for endometrial cytology that would standardize the diagnostic criteria and the terminology used for reporting. METHODS: In previous studies, cytoarchitectural criteria were found to be useful for the cytological assessment of endometrial lesions. To apply these criteria, an appropriate cytological specimen is imperative. In this article, the requirements of an adequate endometrial cytological specimen for the new diagnostic criteria are first discussed. Then, the diagnostic criteria, standardized on a combination of conventional and cytoarchitectural criteria, are presented. Third, terminology that could be used, not only for reporting the histopathological diagnosis, but also for providing better guidance for the gynaecologist to determine further clinical action, is introduced. The proposed reporting format was investigated using endometrial cytology of 58 cases that were cytologically underestimated or overestimated compared to the histopathological diagnosis made on the subsequent endometrial biopsy or surgical specimens. RESULTS: Of the 58 cases, 12 were reassessed as being unsatisfactory for evaluation. Among the remaining 46 cases, 25 of the 27 cases, which had been underestimated and subsequently diagnosed as having endometrial carcinoma or a precursor stage on histopathological examination,were reassessed as recommended for endometrial biopsy. On the other hand, 19 cases overestimated by cytology were all reassessed as not requiring biopsy. CONCLUSIONS: The reporting format for endometrial cytology proposed in this article may improve diagnostic accuracy and reduce the number of patients managed inappropriately.

Identification of a high-risk subgroup in cytology-positive stage IIIA endometrial cancer.

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.

Prognostic value of the colposcopic tumor size in stage IB squamous cervical cancer.

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.

Changes of hemostatic molecular markers after gynecological surgery.

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.

Morphologic analyses of positive peritoneal cytology in endometrial carcinoma.

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.

Assessment of the revised International Federation of Gynecology and obstetrics staging for early invasive squamous cervical cancer.

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.