A morphometric filter improves the diagnostic value of morphometric analyses of frozen histopathological sections from mammary tumours.

Frozen sections of 202 consecutive breast tumour cases were analyzed by morphometric quantitation of nuclear features. Nuclei were selected at random. Conventional light microscope examination of the paraffin-embedded specimens revealed 144 cases of cancer and 56 benign tumours. Using multivariate discriminant analysis of morphometric features, all but two of the benign cases and 79% of the malignant tumours were correctly classified. When a morphometrically based dynamic filter set to exclude 'non-diagnostic' nuclei was used, the correctly classified malignant cases rose to 86% Morphometry is a fast, reproducible and efficient method that can be used in conjunction with the histomorphological diagnosis of mammary frozen sections. The combination of systematic sampling and an objective dynamic filter may be a powerful approach to quantitative analyses of tumours from other sites. However, it is also likely that efficiency can be improved by combining nuclear morphometric features with structural, histochemical and molecular biological data. The combination of traditional histomorphological examination with quantitative information may well increase the diagnostic accuracy in individual patients.     

Morphometry and digital AgNOR analysis in cytological imprints of benign, borderline and malignant serous ovarian tumours

AIM: The aim of the study was to determine values of a quantitative morphometry analysis of nuclear characteristics and argyrophilic nucleolar organizer regions (AgNORs) in differential cytodiagnosis of benign, atypically proliferating (borderline) and malignant serous ovarian tumours. METHODS: Cytological imprints of benign (n = 20), borderline (n = 19) and malignant (n = 20) ovarian serous tumours were analysed. A computerized, digital analysis was used to determine morphometric nuclear features, the number and characteristics of single AgNORs, cluster AgNORs, total AgNOR and AgNOR area/nucleus (relative area) ratio. According to their size AgNORs were classified in three categories. A one-way variance analysis and post hoc test (Scheffé) were used for statistical analysis. RESULTS: The morphometric nuclear analysis showed that benign, borderline and malignant serous ovarian tumours are statistically different (P < 0.001) according to the area and outline, the values being highest in malignant tumours and lowest in the borderline group. Digital analysis of AgNORs in benign, borderline and malignant groups showed that the total AgNOR number increases with progression of the lesion (meaning tumour malignancy) significantly (P < 0.001) between benign and malignant as well as between borderline and malignant serous ovarian tumours (P < 0.001). The progression of the lesion malignancy was accompanied by a significant (P < 0.001) progressive increase of the total and relative AgNOR area per nucleus. The AgNOR size increases from benign to malignant tumours and a statistically significant difference (P < 0.001) was observed in all three groups regarding small and large AgNORs. CONCLUSION: Combining different markers of morphometric nuclear characteristics and AgNOR values could improve differential cytodiagnosis of benign, borderline and malignant serous ovarian tumours.     

A morphometric analysis of individual cell death in bronchial carcinoids

The incidence and morphometric characteristics of individual dead cells have been measured in 51 cases of broncho-pulmonary carcinoid tumours. In both typical and atypical carcinoids, these dead cells were distinguished by nuclei that were significantly smaller and less regular than those of 'intact' tumour parenchymal cells. The proportion of dead to all tumour cells was not significantly different for typical and atypical carcinoids (17 and 13%, respectively). For 33 of these tumours, their ploidy status had also been established. In diploid tumours, the proportion of dead cells was 18% and in aneuploid tumours 12%. The prognosis of patients with atypical carcinoids was significantly worse and such tumours were more commonly aneuploid. Thus the incidence of individual cell death does not appear to be positively associated with poor prognosis in this series. The association between 'necrosis' and poor prognosis commented on in the literature may relate more to a different form of cell death, expressed histopathologically as gross coagulative necrosis, the incidence of which is significantly higher among the atypical, aneuploid tumours.     

A morphometric analysis of individual cell death in bronchial carcinoids

Abstract. The incidence and morphometric characteristics of individual dead cells have been measured in 51 cases of broncho-pulmonary carcinoid tumours. In both typical and atypical carcinoids, these dead cells were distinguished by nuclei that were significantly smaller and less regular than those of 'intact' tumour parenchymal cells. The proportion of dead to all tumour cells was not significantly different for typical and atypical carcinoids (17 and 13%, respectively). For 33 of these tumours, their ploidy status had also been established. In diploid tumours, the proportion of dead cells was 18% and in aneuploid tumours 12%. The prognosis of patients with atypical carcinoids was significantly worse and such tumours were more commonly aneuploid. Thus the incidence of individual cell death does not appear to be positively associated with poor prognosis in this series. The association between 'necrosis' and poor prognosis commented on in the literature may relate more to a different form of cell death, expressed histopathologically as gross coagulative necrosis, the incidence of which is significantly higher among the atypical, aneuploid tumours.     

Automated analysis of rat breast tumors. Comparison of four methods

Chemically-induced malignant rat breast tumors pose diagnostic dilemmas since the majority are well-differentiated, noninvasive papillary lesions that are barely distinguishable from benign papillary lesions. This study compared several automated modalities to see which best separated benign from malignant breast tumors. Thirty-three carcinogen-induced rat breast tumors (13 adenomas, 10 papillary carcinomas and 10 invasive carcinomas) were evaluated by static (image) cytometry (ICM) of integrated optical density, by flow cytometry (FCM) and by two automated morphometric protocols, contextual analysis and single-gland analysis. DNA ploidy analysis, by either ICM or FCM, did not discriminate between the benign and malignant tumors. Contextual analysis correctly identified 11 of 13 benign and 17 of 20 malignant lesions (P less than .01). Single-gland analysis correctly identified all 13 benign and 17 of 20 malignant lesions (P less than .01). No method distinguished invasive from noninvasive carcinomas. The data suggest that architectural features are more important than nuclear features in differentiating benign from malignant rat breast tumors.     

Textural analysis in the diagnosis of benign and malignant breast cells

OBJECTIVE: To study the discriminatory capacity of textural variables to classify the nuclei of breast tumor cells as benign or malignant, using a statistical approach. STUDY DESIGN: Image analysis techniques were used to automatically segment nuclei of cells obtained by fine needle aspiration and Papanicolaou stained. The sample comprised 95 cases of malignant lesions and 47 cases of benign lesions (approximately 25 nuclei per case), and 27 textural variables were measured. Two methods were used to analyze the data: classification and regression trees (CART) and discriminant analysis. RESULTS: The variance in gray levels was the most decisive variable in the CART analysis, correctly classifying 57% and 97% of benign and malignant cases, respectively. Discriminant analysis yielded the best results, correctly classifying 79% and 85% of benign and malignant cases, respectively. CONCLUSION: The classifier obtained by a statistical approach to the textural analysis of Papanicolaou-stained nuclei did not prove useful for diagnostic discrimination. Staining techniques that are not chromatin specific are highly variable, and other features have proven more effective with this type of staining.     

Dna Ploidy Studies of Benign and Malignant Tumours: Comparison of Flow Cytometry and Image Analysis Techniques Using Two Types of Cytological Specimen

DNA ploidy studies were carried out on Feulgen stained smears and cytocentrifuge preparations from 35 malignant tumours and four benign neoplasms using the CAS image analyser. The smears were prepared from scrapings from fresh tumour tissue whereas the cytocentrifuge preparations were prepared from single nuclear suspensions from paraffin-embedded cell blocks from the same tumour. Histograms obtained by image analysis of the tumour scrapes were compared with those obtained on the cytocentrifuge preparations. Concordant results were obtained in four benign tumours (100%) and 32 malignant tumours (91%). The results obtained by image analysis were also compared with results obtained by flow cytometry of the tumour tissue. Discordant results were obtained for three malignant tumours. Possible reasons for the discrepancy include sampling error, tumour heterogeneity and selective loss of cell populations during processing.     

Tumour ploidy, morphometry, histological grading and clinical features in ovarian carcinoma: mutual relations

The relationship between tumour ploidy and qualitative and quantitative histopathology was assessed in a series of 95 ovarian carcinomas. 67% of the tumours were non-diploid (DNA aneuploid). 56% of the early stage (I-II) tumours were non-diploid and 81% of the tumours in advanced (III-IV) stages were aneuploid. Histological grading failed to show a clear relationship between increasing malignancy grade and ploidy. There was a close association between DNA ploidy and nuclear perimeter, area and shortest and longest nuclear diameter: the nuclei of non-diploid tumours were generally larger. Also the number of mitotic figures per square millimeter of epithelium in the microscope image (volume-corrected mitotic index, M/V-index) differed significantly between near-diploid and non-diploid tumours. Discriminant analysis showed that 74% of the learning-set tumours (67% of the test set tumours) could be correctly classified in low-ploidy and high-ploidy categories with morphometric features (nuclear perimeter, M/V-index and volume percentage of epithelium). Characteristic features of non-diploid ovarian tumours--rapid proliferation and large nuclear size--could be assessed with morphometric methods which allowed a relatively large aneuploid tumour group to be distinguished.     

Development and validation of robust metabolism-related gene signature in the prognostic prediction of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. Given metabolic reprogramming in tumours was a crucial hallmark, several studies have demonstrated its value in the diagnostics and surveillance of malignant tumours. The present study aimed to identify a cluster of metabolism-related genes to construct a prediction model for the prognosis of HCC. Multiple cohorts of HCC cases (466 cases) from public datasets were included in the present analysis. (GEO cohort) After identifying a list of metabolism-related genes associated with prognosis, a risk score based on metabolism-related genes was formulated via the LASSO-Cox and LASSO-pcvl algorithms. According to the risk score, patients were stratified into low- and high-risk groups, and further analysis and validation were accordingly conducted. The results revealed that high-risk patients had a significantly worse 5-year overall survival (OS) than low-risk patients in the GEO cohort. (30.0% vs. 57.8%; hazard ratio [HR], 0.411; 95% confidence interval [95% CI], 0.302–0.651; p < 0.001) This observation was confirmed in the external TCGA-LIHC cohort. (34.5% vs. 54.4%; HR 0.452; 95% CI, 0.299–0.681; p < 0.001) To promote the predictive ability of the model, risk score, age, gender and tumour stage were integrated into a nomogram. According to the results of receiver operating characteristic curves and decision curves analysis, the nomogram score possessed a superior predictive ability than conventional factors, which indicate that the risk score combined with clinicopathological features was able to achieve a robust prediction for OS and improve the individualized clinical decision making of HCC patients. In conclusion, the metabolic genes related to OS were identified and developed a metabolism-based predictive model for HCC. Through a series of bioinformatics and statistical analyses, the predictive ability of the model was approved.     

Cytological study of early cervical adenocarcinoma: special reference to the depth of invasion

OBJECTIVE: Early cervical adenocarcinoma (ECA) with a tumour depth of <3 mm has a good prognosis. To clarify the cytological features of ECAs with depth <3 mm, these were compared with those of ECA with 3-5 mm and invasive adenocarcinoma (IA) invading the cervical wall with more than 5 mm in depth. METHODS: The cervical cytological features of ECAs with depth <3 mm (14 cases) were compared with those of ECA with 3-5 mm (four cases) and IA (13 cases). Cytologically, the presence or absence of tumour diathesis, number of atypical cells, crowded cell groups, groups with glandular structures, feathering, groups with palisading borders, rosettes, clusters, cell shape and size, nuclear shape and size, nucleolar shape and size, chromatin distribution, border and character of cytoplasm, and single cell pattern were evaluated. RESULTS: A tumour diathesis was seen in five of 14 ECA <3 mm in depth (36%), all four ECA with 3-5 mm (100%) and 11 of 13 IA with more than 5 mm (85%). Single cells, macronucleoli and coarsely granular chromatin pattern were less frequent in ECA of <3 mm than that in ECA with 3-5 mm and IA. The number of atypical cells and glandular structures in ECA was significantly less than that in IA. Cell crowding, feathering, palisading and rosettes were common in both ECA and IA. CONCLUSION: The characteristic cytological features of ECA with depth <3 mm, having a good prognosis, were clean background, fewer single cells and macronucleoli, and less frequent coarsely granular chromatin pattern compared with those in ECA with 3-5 mm and IA. The number of atypical cells and glandular structures in ECA was significantly less than that in IA. Familiarity with the cytological features of ECA and its mimics is essential.     

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.     

Neuroendocrine cells within colorectal tumours induced by dimethylhydrazine

Summary Colorectal adenocarcinomas were induced in male Wistar rats, by weekly subcutaneous administration of 1,2-dimethylhydrazine, classified according to the degree of differentiation and submitted to immunocytochemistry for the peptides cholecystokinin (CCK), gastrin, gastric inhibitory polypeptide (GIP), glucagon, neurotensin, pancreatic polypeptide (PP), peptide YY (PYY), somatostatin and vasoactive intestinal polypeptide (VIP) and the biogenic monoamine 5-hydroxytryptamine. Well- or moderately well-differentiated adenocarcinomas comprised 46% of the tumour population, only 4% were poorly-differentiated adenocarcinomas, and the remaining 50% possessed a mixture of these two morphologies. Glucagon, PYY and 5-hydroxytryptamine immunoreactive cells were frequently observed within well- or moderately well-differentiated tumours and within such regions of tumours possessing a mixed morphological pattern. The tumours contained no cells immunoreactive for any of the peptides not normally located within the colorectum, nor did they contain cells immunoreactive for somatostatin and VIP, although known positive controls did stain. Poorly-differentiated tumours and portions of tumours of mixed type, were consistently negative. 5-hydroxytryptamine was the most frequently located of the three antigens, being detected in 87% of the moderately well-differentiated tumours and 32% of the tumours with mixed morphologies. 11% of moderately well-differentiated tumours possessed 5-hydroxytryptamine positive cells in such profusion that they contributed significantly to the tumour mass. The distribution of glucagon-and PYY-immunoreactive cells was similar, although they occurred with a lower frequency, presumably corresponding to their lower numbers within the normal colorectal mucosa. Additionally, these two peptide immunoreactivities were colocalized in the majority of cells, although some cells contained only one antigen. The immense numbers of cells immunoreactive for peptides and monoamine in a significant proportion of colorectal adenocarcinomas suggests that they have arisen from multipotential endodermal stem cells within the tumours and are not part of the normal epithelial population being engulfed as the tumour grows.     

Long non-coding RNA LINC00607 silencing exerts antioncogenic effects on thyroid cancer through the CASP9 Promoter methylation

Thyroid cancer (TC) was the most frequent thyroid malignant tumour, accounting for about 1% of all malignant tumours. Some long non-coding RNAs (lncRNAs) have been reported to exert essential tumour promotion effects, while caspase-9 (CASP9) gene could play a promotive role in the cell apoptosis in TC. However, whether they have a specific effect on TC remains unclear. Hence, this study aims to explore the relationship between LINC00607 and CASP9, and its effect in TC. LINC00607 expression in the TC tissues and cell lines was determined. Then, we explored the combination effect between a LINC00607 and a methylation inhibitor 5-Aza-dc in doxorubicin-resistant ARO cells using colony formation assay, flow cytometry, WST-1 and EdU assay, as well as in vivo tumour growth assay. Besides, the dual-luciferase reporter gene assay, RIP, ChIP, methylation-specific PCR and BSP method were employed to detect the relationship between LINC00607 and CASP9 and its methylation. LINC00607 expression was up-regulated in the doxorubicin-resistant TC cell lines and tissues and negatively correlated to the poor prognosis of TC patients. Knockdown of LINC00607 suppressed doxorubicin resistance, proliferation and colony formation, and promoted cell apoptosis of TC cells in vitro, as well as suppressed tumour growth in vivo, whereas LINC00607 overexpression was observed to exercise the opposite effects. Notably, it was also revealed that LINC00607 down-regulated the CASP9 expression by promoting CASP9 promoter methylation. In conclusion, LINC00607 could inhibit the apoptosis and augment the doxorubicin resistance of TC cells by decreasing CASP9 expression, which might provide a novel therapeutic target for TC treatment.     

The 3-dimensional organization of the nucleoli of benign and malignant tumor cells from different human organs]

The method of ultrathin serial sections was used to perform a comparative ultrastructural and 3-dimensional analysis of nucleoli for the following variants of human tumours: benign (fibroadenoma) and malignant (infiltrating ductal carcinoma) tumours of one organ (mammary gland); malignant tumours of epidermal genesis in different organs (squamous cell carcinomas of skin, larynx, lung, gullet, uterus); two forms of malignant tumours (squamous cell and small cell carcinomas) of one organ (lung). The spatial models of nucleoli in these tumour cells are given. The specific signs in architecture of tumour nucleoli was found. Nucleoli of fibroadenomas have well pronounced 1-4 fibrillar centres forming a united system with a lacunar component and intranucleolar chromatin. Unlike benign tumour cells, nucleoli of infiltrating ductal carcinomas are characterized by large, prominent nucleoli containing giant, multiform fibrillar centres with a complicated surface, a well developed granular component and an unusually organized lacunar system. In squamous cell carcinomas of various localization, active, hypertrophied nucleoli with pseudonucleolonemal organization were found. The small cell carcinoma of lung differs from the squamous cell cancer of the same organ by dense, fibrillar nucleoli with a small amount of granular component located on the periphery of the nucleolar body. Nucleolar type reflecting the functional state of malignization process may serve as an additional diagnostic criterion for tumour identification.     

Stereotactic biopsy and cytological diagnosis of solid and cystic intracranial lesions

Cytological smears from 115 consecutive cases of stereotactic biopsies of intracranial lesions were reviewed. Ninety-five lesions were solid and 20 cystic. Material from 90 solid and 13 cystic lesions was sent both for cytological and histological examination. In 66 of the solid lesions, the cytological diagnosis was confirmed by histology (five were benign lesions and 61 malignant tumours: 56 primary brain tumours, three metastases and two lymphomas). In 24 cases with discrepant cytology and histology, the histology was inconclusive or insufficient in 14 cases, while cytology established the diagnosis of astrocytoma grade II (seven cases), metastases (two cases), gliosis (one case) and benign (four cases). Necrosis of tumour type was observed cytologically in six patients representing glioblastoma (two cases), anaplastic astrocytoma (one case), lymphoma (one case) and normal brain (two cases) histologically. Three cases reported cytologically as benign were primary brain tumour (two cases) and gliosis (one case). One smear of a glioblastoma was insufficient for cytological diagnosis. Cystic lesions were cytologically benign in 17 cases and malignant in three cases. Histology from the cyst wall confirmed the malignant diagnosis in three cases and showed tumour in six more cases, a benign process (two cases), changes induced by radiotherapy for arteriovenous malformation (one case) and insufficient material (one case). In conclusion, cytology from solid brain lesion allows an accurate diagnosis and subtyping of tumours in a majority of cases, and can thus be used to choose type of therapy. In cystic brain tumours, however, examination of the cystic fluid, is often inconclusive and a biopsy from the cyst wall should be performed if there is clinical or radiological suspicion of tumour.     

Computerized morphometric quantitation of cellular features in splenocytes from normal and nutrient-restricted mice

The morphometric analysis of splenocytes reveals quantitative changes in the chromatin and cytoplasm that may be used to distinguish between cells from normally fed animals and cells from subjects fed restricted diets. Analysis of Feulgen-stained and Papanicolaou-stained cells from mice fed normal diets and mice fed either calorie-restricted diets or isocaloric but protein-restricted diets showed an approximately 10% reduction in the nuclear area and in the total optical density (TOD) of stained chromatin in cells from diet-restricted mice. Some changes in chromatin texture features were also observed. Utilization of nuclear area, TOD and one textural feature in a linear discriminant analysis produced a distinct separation of the cells from dietary-restricted mice and the cells from normally fed subjects; this was observed with both Feulgen-stained and Papanicolaou-stained cells. The cellular effect of dietary restriction was more noticeable in the cytoplasm than in the nucleoplasm; Papanicolaou-stained cells from diet-restricted animals showed a 23% reduction in the cytoplasmic TOD and a 10% reduction in the nuclear TOD. This study shows that computerized morphometric analysis may be used in place of or in conjunction with other measurement procedures and chemical tests to quantitate and differentiate cells subjected to different types and levels of nutritional stress.     

Quantitative ultrastructural study of nuclei from exfoliated benign and malignant mesothelial cells and metastatic adenocarcinoma cells

Various approaches, including morphometric image analysis, are currently being used to improve the distinction between diffuse mesothelioma and metastatic adenocarcinoma of the serous membranes. Since exfoliated cells of malignant mesotheliomas were thought to have nuclear profile contours with greater irregularity than the similar profiles in metastatic adenocarcinoma cells in pleural effusions, this and other nuclear parameters were measured in ultrastructurally examined preparations from three cases of reactive mesothelial hyperplasia, seven examples of diffuse mesothelioma and three cases of metastatic adenocarcinoma (with primaries in the ovary, esophagus and prostate). Contrary to the subjective impression, the nuclei in metastatic adenocarcinomas actually had a mean nuclear contour index greater than that found in diffuse mesotheliomas; statistically, the difference was not significant. Likewise, such other nuclear parameters as nuclear area, condensed chromatin area and contour index, percentage of condensed chromatin and number of condensed chromatin clumps per nuclear profile did not discriminate between malignant mesotheliomas and adenocarcinomas metastatic to pleural surfaces. These morphometric results quantitate the similarities in nuclear size, nuclear shape and condensed chromatin arrangement in these two types of tumor and explain why the cytopathologist has such great difficulty in distinguishing between exfoliated mesothelioma and adenocarcinoma cells in most cases.     

Localisation and expression of aquaporin subtypes in epithelial ovarian tumours

To characterise AQP subtype localisation and expression in epithelial ovarian tumours, immunohistochemistry was used to assess the localisation and expression of AQP1-9 in 30 benign tumour cases, 30 borderline tumour cases, 50 malignant tumour cases and 20 normal ovarian tissue cases. Multiple AQP subtypes were expressed in epithelial ovarian tumours, with each AQP subtype displaying a different pattern of localisation and expression. AQP1 was mainly expressed in the microvascular endothelium, and AQP 2-9 were mainly expressed in tumour cells. Most AQP subtypes co-localised in the basolateral membranes of the epithelia of benign tumours and plasma membranes of malignant tumour cells. The positive rates for AQP1, 5, 6, 7, 8, and 9 were over 50%, but those for AQP2, 3 and 4 were only 10-40%. The expression of AQP1, 5 and 9 in malignant and borderline tumours was significantly higher than that in benign tumours (P<0.05) and normal ovarian tissue (P<0.05). However, AQP6 expression in ovarian malignant and borderline tumours was significantly lower than that in benign tumours (P<0.01) or normal ovarian tissue (P<0.01). AQP1 expression was increased in cases with ascites volumes greater than 1000 mL (P<0.05), AQP5 expression was greater in cases with lymph node metastasis (P<0.05), and more AQP9 expression was observed in G3 cases versus G1 and G2 cases (P<0.01). These results suggest that changes in the distribution and expression of AQP subtypes may be involved in ovarian carcinogenesis. This study presents a novel avenue of research that could illuminate the mechanism of ovarian carcinogenesis and treatment.     

Clinico-cytological study of uterine papillary serous carcinoma

OBJECTIVE: The aim of this study was to determine whether or not we could distinguish uterine papillary serous carcinoma (UPSC) from other types of endometrial cancer by cytology. METHODS: We examined the cytological findings of the endometrium from five cases with UPSC and compared them with 10 cases with endometrioid adenocarcinoma, grade 1 (G1). A morphometric analysis was performed. Cytological samples from the cervix and ascites of the patients with UPSC were also reviewed. RESULTS: All five patients had FIGO stage III and IV tumours. Three patients died of the disease and two are still alive with disease. The tumour cells of UPSC tended to be shed in papillary clusters with a tumour diathesis. Psammoma bodies were seen only in UPSC. The frequency of irregular-shaped nuclei, membrane thickness and eccentric nuclei in UPSC was higher than in G1. The chromatin pattern was coarsely granular, and both anisonucleosis and bare nuclei were prominent in UPSC. Cytomorphometrically, the maximum diameter of the nuclei in UPSC was significantly greater than that in G1. The nucleoli were also more often seen in UPSC than in G1. The findings of the nuclei and nucleoli in the cervical and peritoneal fluid cytology closely resembled those in endometrial smears. The features of the cervical smears and peritoneal fluid cytology were different from those of endometrial cytology regarding clear background and small clusters of cells. CONCLUSION: As the endometrial cytology findings accurately suggested the histological diagnosis of UPSC, the diagnosis of UPSC was confirmed in this study by endometrial cytology. The cytological diagnosis of UPSC should be based on the findings of tumour diathesis, psammoma bodies and papillary clusters composed of tumour cells with enlarged nuclei and numerous nucleoli.