Progression curves for endometrial lesions

OBJECTIVE: To derive a numeric measure for the progression of endometrial lesions as a baseline study for an eventual assessment of chemopreventive intervention efficacy. STUDY DESIGN: Tissue sections from normal endometrium at the proliferative and secretory phase, simple hyperplasia, atypical hyperplasia from cases free of concomitant adenocarcinoma and adenocarcinoma of the endometrium were recorded at high spatial resolution. Six cases from each diagnostic category were chosen as "typical," and 60 epithelial nuclei were randomly selected for measurement for each case. Discriminant analyses were carried out to derive a direction of progressive change in feature space and to correct the progression curve for the presence of cells not expressing progressive change among the random sample of nuclei. RESULTS: A well-conditioned progression curve was derived based on the mean discriminant function scores for each diagnostic category and the mean nuclear abnormality of the nuclei in each category, as expressed by their deviation in feature values from normal reference nuclei. The lesion signatures showed a clear trend toward extension into the range of higher nuclear abnormalities with increasing progression. There was an indication that abnormal endometrial lesions may comprise cases with distinctly different degrees of nuclear abnormality. CONCLUSION: A numeric assessment of lesion progression for endometrial lesions, based on karyometric measurements, is possible. The data suggest that additional analysis may provide further characterizing information for individual lesions.     

A karyometric approach to the characterization of atypical endometrial hyperplasia with and without co-occurring adenocarcinoma

OBJECTIVE: To develop a karyometric image analysis approach to distinguishing atypical endometrial hyperplasia with and without co-occurring adenocarcinoma. STUDY DESIGN: Six cases of atypical hyperplasia without and 6 cases with co-occurring adenocarcinoma, 4 cases of normal endometrium and 3 cases of adenocarcinoma were identified. From each case 100 nuclei were measured in representative diagnostic areas identified by an experienced pathologist. Discriminant analyses were performed. An unsupervised learning algorithm was applied to define and characterize different nuclear phenotypes, and those data were used to identify cases with co-occurring adenocarcinoma. RESULTS: Discriminant analysis showed that nuclei from atypical hyperplasia and atypical hyperplasia with co-occurring adenocarcinoma are statistically different. The unsupervised learning algorithm revealed differences in nuclear subpopulations that can be used to correctly identify an estimated 85% of individual cases. CONCLUSION: Nuclei from atypical hyperplasia without and with co-occurring adenocarcinoma have statistically different karyometric characteristics that may facilitate case classification.     

Karyometry in endometrial adenocarcinoma of different grades

OBJECTIVE: To characterize nuclei from adenocarcinoma of the endometrium of different grades in order to establish whether significantly different nuclear subpopulations exist. STUDY DESIGN: A total of 1,400 nuclei from 14 cases of adenocarcinoma of the endometrium of grades 1, 2 and 3 were recorded, and 600 nucleifrom normal, secretory phase glandular endometrial epithelium were used as a reference data set. Karyometric features were computed and a discriminant function derived to define a trend in feature values for nuclei from lesions of different grades. The nuclei from lesions of different grades were processed by a nonsupervised learning algorithm in an effort to detect and define subpopulations. RESULTS: Nuclei from grade 1 lesions represented a near-diploid stemline, whereas nuclei from grade 3 lesions formed an aneuploid set with a mode around 3N. The existence of three subpopulations with statistically different nuclear chromatin patterns could be shown for nuclei from each grade. In each grade these three subpopulations occupied the same relative position in feature space. For grade 1 lesions all three subpopulations were near diploid, for grade 3 lesions all three were approximately triploid. CONCLUSION: The nuclei in adenocarcinoma of the endometrium form a heterogeneous set, with subpopulations of distinctly different chromatin patterns and different ploidy. This should be taken into consideration in assessing the efficacy of chemopreventive intervention.     

人滋养细胞表面抗原（Trop-2）在病变子宫内膜中表达的研究

摘要 目的：探讨人滋养细胞表面抗原（trophoblast cell-surface antigens2,Trop-2）在病变子宫内膜中的表达及其临床相关性。方法：采用免疫组化法检测100例正常子宫内膜或病变子宫内膜组织中Trop-2蛋白的表达,其中单纯增生子宫内膜患者26例,复杂或不典型增生子宫内膜患者34例,子宫内膜腺癌患者20例,对照组为20例增生期子宫内膜患者。结果：免疫组织化学法研究结果显示,Trop-2蛋白在正常增生子宫内膜和单纯性增生子宫内膜中几乎不表达,在复杂或不典型增生子宫内膜组织中以及子宫内膜腺癌呈阳性表达。主要分布在细胞膜上,阳性率分别为35.29 %和65.00 %,经过对比子宫内膜癌组的阳性表达率显著高于复杂型或伴不典型增生子宫内膜组的阳性表达率（P<0.05）,且复杂型或伴不典型增生子宫内膜组的阳性表达率显著高于单纯性增生子宫内膜组（P<0.05）,其表达水平随内膜病变程度的加重而升高,呈正相关关系（P＜0.05）。结论：Trop-2蛋白在子宫内膜病变中的表达与其严重程度一致,可反映子宫内膜病变的发生发展,或可作为判断其严重程度的指标。     

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.     

Endometrial hyperplasia with berrylike squamous metaplasia and pilomatrixomalike shadow cells. Report of an intriguing cytohistologic case

BACKGROUND: The usefulness of endometrial cytology as a diagnostic method in asymptomatic women, especially in postmenopause, in the interpretation of composite pictures characterized by borderline features between atypical hyperplasia and well-differentiated adenocarcinoma, especially if associated metaplastic features are present, is somewhat controversial. CASE: An asymptomatic, 50-year-old, postmenopausal woman underwent a Pap smear and endometrial cytology for routine screening, disclosing three-dimensional, sometimes pseudopapillary groupings of hyperplastic endometrial glandular cells with focal atypia in direct continuity with large, squamoid cells of the keratinizing type and shadow cells. Histologic examination of endometrial tissue was advised, and two subsequent endometrial biopsies and hysteroscopic ablation were performed. The borderline character of the lesion (complex atypical hyperplasia vs. well-differentiated adenocarcinoma) with concomitant squamous metaplasia and pilomatrixomalike shadow cells prevented diagnostic agreement between several pathologists. CONCLUSION: Diagnostic cytology with direct endometrial sampling represents a valuable diagnostic screening tool for the differential diagnosis between normal and pathologic endometrium, a mucosal picture that deserves a subsequent (histologic) diagnostic procedure. In a few cases, as in the one presented above, even histologic examination, especially of so-called borderline lesions, reveals squamous or other types of metaplasia that can lead to interobserver discrepancies.     

Digital image analysis of silver-stained nucleolar organizer region--associated proteins in endometrial cytologic samples

OBJECTIVE: Digital image analysis was applied to determine the number, area and size of silver-stained nucleolar organizer regions (AgNORs) in cytologic samples from curettage in normal, hyperplastic and malignant endometrium. STUDY DESIGN: Thirty-two archival cytologic smears from curettage (previously stained by the Papanicolaou method) with the histologic diagnosis (4 inactive endometrium, 5 secretion, 5 proliferation, 5 simple hyperplasia, 5 complex hyperplasia, 3 atypical hyperplasia, 5 adenocarcinoma, grade 1) were analyzed with the AgNOR technique. Count, area and size of AgNORs were analyzed in 50 cells per sample using a magnification of 1,000x. Quantitative analysis was performed on an SFORM digital imaging system. Data were analyzed with the SPSS/PC+ program. Mann-Whitney and chi 2 tests were performed. RESULTS: The average value of AgNOR count increased from normal to hyperplastic endometrium and well-differentiated adenocarcinoma. Differences were significant except between atypical hyperplasia and adenocarcinoma. Four, five and more AgNORs in 40% or more of the nuclei were found in complex and atypical hyperplasia and adenocarcinoma. Proliferation, and simple and atypical hyperplasia had similar mean values of AgNOR area. The mean total AgNOR area value increased from normal to hyperplastic had similar mean values of AgNOR area. The mean total AgNOR area value increased from normal to hyperplastic and well-differentiated adenocarcinoma. Differences were statistically significant. AgNOR size in well-differentiated adenocarcinoma was significantly different from that in normal endometrium and different grades of hyperplasia. CONCLUSION: Digital image analysis of AgNOR count, area and size enabled a distinction to be made between normal, hyperplastic and malignant endometrium.     

Potential of the learning vector quantizer in the cell classification of endometrial lesions in postmenopausal women

OBJECTIVE: To investigate the potential of artificial neural networks for cell identification in endometrial lesions from postmenopausal women. STUDY DESIGN: The study was performed on cytologic material obtained by the Gynoscann endometrial cell samplerfrom 12 cases of atrophic endometrium, 48 cases of hyperplasia without cytologic atypia (18 cases of simple hyperplasia and 30 cases of complex hyperplasia), 12 cases of hyperplasia with cytologic atypia (complex atypical hyperplasia) and 48 cases of adenocarcinoma (30 cases of well-differentiated, 12 cases of moderately differentiated and 6 cases of poorly differentiated carcinoma). From each case approximately 100 cells were examined using a custom image analysis system. A learning vector quantizer (LVQ) identified the collected data. RESULTS: Investigation of cells from Endometrial Alterations with LVQ proved that according to the nuclear characteristics, as expressed by morphometric and textural measures, the endometrial cells from postmenopausal women may be identified as belonging to one of thefollowing three groups: atrophy, hyperplasia without cytologic atypia (simple and complex hyperplasia) and malignant neoplastic lesions (atypical complex and adenocarcinoma). CONCLUSION: The role of nuclear morphologic features in the cytologic diagnosis of endometrial alterations was confirmed. The overlap in thefeature space observed indicates that cell characteristics do not form strictly separate clusters. Thatfact explains the difficulty that morphologists have with the reproducible identification of cells from endometrial lesions in postmenopausal women. Application of LVQ offers a good classification at the cell level and promises to be a powerful toolfor classification on the individual patient level andfor the clarification of the natural history of endometrial pathology.     

Karyometric image analysis for intraepithelial and invasive cervical lesions

OBJECTIVE: To derive an objective, numeric measure for the progression of intraepithelial and invasive squamous cell cervical lesions. STUDY DESIGN: Thin-layer cervical cytology preparations from colposcopically confirmed normal cervix, low grade squamous intraepithelial lesions, high grade squamous intraepithelial lesions and carcinoma were identified from a cross-sectional study. Fifty-nine cases representing 4 diagnostic categories were selected, and 2,375 nuclei from epithelial cells representative of the diagnostic category were randomly selected for imaging and measurement from these cases. Additionally, 1,378 visually normal appearing intermediate cells from low and high grade squamous intraepithelial lesions, as well as from carcinoma cases, were identified for analysis. The nuclei were quantitatively characterized, and discriminant analyses were performed to derive a progression curve from normal cytology to carcinoma. RESULTS: The lesion signatures show a clear increase in nuclear abnormality with increasing progression. A progression curve was derived based on mean discriminant function scores for each diagnostic category and on the mean nuclear abnormality values for the nuclei in each category, as expressed by their deviation in feature values from normal reference nuclei. CONCLUSION: A numeric assessment of lesion progression for cervical precancerous and cancerous lesions based on karyometric measurements is possible and may provide an objective, precise characterization of each lesion as well as a basis for improved performance in automated cytology-based cervical cancer screening.     

Karyometry of infiltrating breast lesions

OBJECTIVE: To characterize nuclei from well-differentiated, moderately differentiated and poorly differentiated lesions of invasive breast cancer by karyometry and to test the hypothesis that these diagnostic categories form homogeneous sets. STUDY DESIGN: Histopathologic sections from 6 cases of well-differentiated, 11 cases of moderately differentiated and 17 cases of poorly differentiated ductal carcinomas were digitally recorded. From each case 100 nuclei were segmented and analyzed by karyometry. A discriminant analysis was performed, and nuclear and lesion signatures were computed. The nonsupervised learning algorithm P-index was applied. A progression curve per diagnostic category based on mean nuclear abnormality and a discriminant function score was derived. RESULTS: The well-differentiated lesions formed a homogeneous set, but both the moderately and poorly differentiated lesions showed 2 significantly different subpopulations with nuclei of substantially different nuclear abnormality and progression. CONCLUSION: The visual histopathologic diagnostic assessment of these lesions was based on an evaluation of both tissue architectural criteria and nuclear criteria. Here, only the pattern of nuclear chromatin was evaluated. Cases belonging to the same diagnostic category as assessed by their differentiation may be further characterized by the extent to which the nuclei deviate from normal. There was substantial case-to-case heterogeneity in these invasive lesions.     

Nuclear chromatin characteristics of breast solid pattern ductal carcinoma in situ.

OBJECTIVE: To characterize nuclei from breast solid pattern ductal carcinoma in situ (DCIS) by their karyometric features and to search for the presence of statistically significantly different subsets of nuclei. STUDY DESIGN: One hundred nuclei from each of 6 normal, 13 solid DCIS, (9 low and intermediate grade and 4 high grade DCIS) histopathologic samples of breast tissue were digitally recorded. Karyometric features were computed and subjected to a nonsupervised learning algorithm (P-index) to identify significantly different subgroups. RESULTS: Nuclei in low grade lesions displayed a diploid/near diploid pattern, while the majority of intermediate grade lesions fell into a range beyond 5N. The high grade lesions showed substantial genomic instability and represented three statistically different subsets or phenotypes. CONCLUSION: There is a progression of nuclear abnormality from low grade to high grade DCIS. The nuclei from high grade DCIS form a heterogeneous set that represents three phenotypes. One of these phenotypes shows a nuclear chromatin pattern that more closely resembles poorly differentiated, infiltrating disease. The observation of such a phenotype may have prognostic implications.     

DNA image cytometry in the differential diagnosis of endometrial hyperplasia and adenocarcinoma

OBJECTIVE: To test the value of DNA image cytometry in the differential diagnosis of hyperplastic endometrial lesions and endometrial carcinoma on a series of 153 cases of simple hyperplasia (n = 71), complex hyperplasia (n = 28), complex atypical hyperplasia (n = 11) and endometrial adenocarcinoma (n = 43). STUDY DESIGN: Monolayer smears were prepared from three 50-micron-thick sections by a cell separation technique and were stained according to Feulgen. The DNA content of 250 epithelial cells, chosen randomly, was determined using a TV image analysis system (CM-1, Hund, Wetzlar, Germany). The DNA content of 30 lymphocytes served as an internal standard for the normal diploid value in every case. Different DNA cytometric parameters and the mean nuclear area were calculated. RESULTS: Cases of adenocarcinoma and complex atypical hyperplasia (n = 54) were defined as clinically "positive" as these patients are normally treated by hysterectomy. The remaining cases of simple and complex hyperplasia (n = 99) were interpreted as clinically "negative" as conservative therapy is usually preferred. Requesting a specificity of > 90%, high sensitivity rates were calculated for ploidy imbalance (94%), mean ploidy (91%), diploid deviation quotient (91%), DNA stemline ploidy (87%) and 2c deviation index (85%), based on suitable thresholds. Entropy (76%), 5c exceeding events (63%), mean nuclear area (48%) and 9c exceeding events (6%) revealed lower sensitivity values. 5c Exceeding events (P = .0117) and mean nuclear area (P = .0392) were helpful in differentiating between atypical hyperplasia and endometrial carcinoma as the data distribution was significantly different with the U test. CONCLUSION: Our results indicate that DNA single cell cytometry is a highly relevant tool in the differential diagnosis of endometrial lesions and could be used as a complementary diagnostic method, especially in histomorphologically difficult cases.     

FAS在子宫内膜样腺癌及其癌前病变中的表达及意义

目的研究脂肪酸合成酶(Fatty acid synthase FAS)在子宫内膜样腺癌及其癌前病变中的表达以及与临床病理意义。方法 37例子宫内膜样腺癌、21例子宫内膜非典型增生、23例子宫内膜复杂性增生、17例子宫内膜单纯性增生及11例增生期子宫内膜中FAS的表达情况,结合临床病理参数并进行统计学分析。结果 FAS在子宫内膜样腺癌、子宫内膜非典型增生、子宫内膜复杂性增生、子宫内膜单纯性增生及增生期子宫内膜中均有表达,其阳性表达率依次为81.1%、57.1%、56.5%、52.9%、45.5%。子宫内膜样腺癌中FAS的阳性表达率明显高于增生期子宫内膜、子宫内膜单纯性增生、子宫内膜复杂性增生及子宫内膜非典型增生(P<0.05)。FAS的阳性表达率在浸润深度≥1/2肌层的子宫内膜样腺癌明显高于浸润深度<1/2肌层者(P<0.05)。FAS的表达与年龄及组织学分级无显著差异性(P>0.05)。在子宫内膜样腺癌中FAS的表达与ER有关(P<0.05)结论本研究提示FAS的表达可能与子宫内膜样腺癌的发生、发展有关。FAS可以作为提示子宫内膜样腺癌预后的一个新的参考指标。部分ER阳性的子宫内膜样腺癌的发生、发展可能与FA...     

Cytologic findings in endometrial hyperplasia

The cytologic findings in 15 endometrial hyperplasias were compared with those of normal endometrium and well-differentiated endometrial adenocarcinoma. Differences in tumor diathesis, hypercellularity, uneven internuclear distance, severe piling up of nuclei, anisokaryosis, nuclear size and macronucleoli were the main cytologic findings that were noted among the three conditions. These features varied in the different types of endometrial hyperplasia. It is not clear that these cytologic findings can be used to cytologically diagnose endometrial hyperplasia because some of the findings involve subjective judgments by different cytologists. Further studies on larger series of cases will be necessary to establish the cytologic criteria for the correct interpretation of endometrial abnormalities.     

Karyometry in Barrett's esophagus

OBJECTIVE: To derive a progression curve for lesions in Barrett's esophagus based on karyometric features. STUDY DESIGN: High-resolution imagery of 900 nuclei from normal gastric tissue, Barrett's metaplasia, Barrett's high grade dysplasia and adenocarcinoma of the esophagus was recorded. Karyometric features were computed, and nuclear signatures and lesion signatures for these lesions were derived. A progression curve was defined. RESULTS: Esophageal lesions were distinctly different from the normal gastric fundus tissue, with nuclei from Barrett's metaplasia deviating from normal almost as much as nuclei from high grade dysplasia and adenocarcinoma. There was considerable case-to-case variability and overlap between lesions histologically assigned to different diagnostic categories. CONCLUSION: The karyometric data suggest that Barrett's metaplasia is a more developed lesion than previously assumed.     

凋亡抑制蛋白Survivin在增生性子宫内膜及子宫内膜癌中的表达

目的　研究凋亡抑制蛋白Survivin在正常子宫内膜、增生性子宫内膜及子宫内膜癌中的表达 ,探讨Survivin蛋白在子宫内膜癌发生发展中的作用及其作为预后判断因子的可行性。方法　应用免疫组织化学S P法 ,检测 15例正常子宫内膜、 2 6例增生性子宫内膜及 33例子宫内膜腺癌中Survivin蛋白的表达 ,并结合临床病理特点进行分析。结果　Sur vivin蛋白的阳性表达率在正常子宫内膜 ,增生性子宫内膜及子宫内膜癌中呈上升趋势。正常子宫内膜仅在增生期有微弱的表达 ,而分泌期及绝经期子宫内膜表达全为阴性 ;而Survivin在子宫内膜癌中及不典型增生中的阳性表达率分别为87 88%和 70 0 % ,均明显高于正常内膜 (P <0 0 5 ) ,且两者的过表达率均高于单纯和复合型增生及正常内膜 (P <0 0 5 ) ,但子宫内膜癌中与不典型增生中的Survivin表达率及过表达率均无明显差异。子宫内膜癌中Survivin的表达强度与组织学分级及手术病理分期明显相关 (P <0 0 5 ) ,但与肌层浸润无关。结论　Survivin作为凋亡相关因子和细胞周期调节因子 ,可能参与了与子宫内膜癌的发生发展 ,其过度表达与预后不良相关 ,其检测可为子宫内膜癌的早期诊断、辅助治疗及预后判断提供理论依据。     

The premalignant disease of the endometrium: endometrial intraepithelial neoplasia

The WHO 1994 classification for endometrial hyperplasias is based on the morphologic features of the lesions. This system characterizes the nuclear cytologic morphology as typical or atypical and describes the glandular architectural pattern as simple or complex. The main problem of this classification is the poor reproducibility. Although the predictive value of the atypical category is high, there are many typical hyperplasia cases with cancer progression. Modern molecular data related to endometrial tumorigenesis and precise computerized morphometric analysis have identified the lesion that may be considered as a precursor of endometrioid adenocarcinoma. By definition, this endometrial intraepithelial neoplasia (EIN) is a clonal proliferation of architecturally and cytologically altered endometrial glands which are prone to malignant transformation to endometrioid (type I) endometrial adenocarcinoma. The morphometric basis of EIN diagnosis is the D-score (DS), which is a logical combination of three morphometric features that represent the glandular complexity, glandular volume and cytological alterations. PTEN inactivation and K-ras mutation are the earliest genetic changes that can be revealed in these lesions. Hyperplasia cases that do not fit into the EIN categories are considered as benign or hormonal endometrial hyperplasia. This is the theoretical basis of a new classification system in premalignant endometrial diseases. Retrospective clinical data proved the high predictive value of the EIN scheme, so the decision on therapy can be more established. The reproducibility is excellent with application of precise definitions and PTEN immunohistochemistry. In the "Blue book" published in 2003 the WHO introduces the new morphometric- and molecular-based EIN system, and recommends it as an alternative classification method.     

P63在子宫内膜样腺癌的表达及意义

目的检测正常子宫内膜、子宫内膜增生症和子宫内膜样腺癌（endometriod adenocarcinoma,EC）组织中P63的表达,探讨P63与子宫内膜样腺癌发生、发展及预后的关系。方法采用免疫组化SP法检测正常子宫内膜（20例）,子宫内膜增生症（20例）,子宫内膜样腺癌（50例）组织中P63蛋白的表达。结果（1）正常子宫内膜中仅1例增生期内膜中有P63表达,阳性细胞零星分布于极个别腺体的基底部。子宫内膜增生症和子宫内膜样腺癌组织中,P63阳性细胞常相对集中分布于某一区域的腺体或实性巢,染色强。（2）EC组和子宫内膜增生症组P63的阳性率分别为46％和50％,与正常子宫内膜组（5．0％）比较差异有显著性护〈0．05）。子宫内膜增生症组P63的阳性率与EC组比较差异无显著性（P〉0．05）。（3）P63的表达与EC的分化程度无关（P〉0．05）。结论（1）EC组织中P63阳性细胞可能来源于胚胎时期的未分化细胞,具有多向分化的潜能。（2）P63与EC的发生发展有关,可能起癌基因的作用。（3）P63在子宫内膜增生症组织中高表达,表明P63与子宫内膜的异常增生相关。     

Cytological criteria of endometrial lesions with emphasis on stromal and epithelial cell clusters: result of 8 years of experience with intrauterine sampling

Objective:  There are a number of unresolved issues in endometrial cytology. They include the significance of nuclear atypia for the diagnosis of grade1 adenocarcinoma (G1AC) and atypical endometrial hyperplasia (AEH), cytological criteria of endometrial hyperplasia without atypia, and recognition of stromal cell cluster (SC) and its distinction from epithelial cell cluster (EC).
Methods:  We examined nuclear atypia, SC and EC in typical cases of five categories: normal endometrium (NEM), simple endometrial hyperplasia without atypia (SEH), complex endometrial hyperplasia without atypia (CEH), G1AC and grade2 adenocarcinoma (G2AC). We classified EC into four types: simple EC (SPEC), large regular EC (LREC), large irregular EC (LIEC) and small irregular EC (SIEC). Based on the results, we developed criteria of endometrial cytology and have evaluated 13 639 cases over 8 years.
Results:  Nuclear atypia was significantly more frequent in G2AC than in any of the other four categories ( P  <   0.001). SC was significantly more frequent in NEM and SEH than in the other three categories ( P  <   0.001). G1AC and G2AC showed significantly higher frequency of LIEC than the other three categories ( P  <   0.001). CEH exhibited significantly higher frequency of LREC than the four categories ( P  <   0.001). The sensitivity and the specificity was 88.8% and 99.0% respectively.
Conclusions:  We could diagnose G1AC, G2AC and CEH with high accuracy using the established criteria mainly based on SC and EC. We think that the criteria may facilitate an effective screening and an objective interpretation of endometrial samples.