Cervicovaginal and endometrial cytology in ovarian cancer

The clinical significance of cytologic examination was studied in 114 patients with ovarian cancer who had received preoperative cytologic examinations. The overall positive rate of the cytologic examinations was 26.3% (30 of 114): 22 (19.3%) of the 114 cases had positive cervicovaginal smears while 13 of 31 endometrial aspiration smears (41.9%) were positive. The positive rate was not related to the volume of ascites but rather to its presence or absence. Thus, if ascites was observed, the positive rate was about 2.1 times higher than if it was absent. In two of four cases of ovarian cancer with no endometrial invasion but a positive cytologic examination of ascitic fluid, fallopian tube specimens contained cancer cells; this suggests that ovarian cancer cells may reach the cervix and/or vagina by passing through the fallopian tube, particularly if ascites is present. Since cytologic examination, especially of endometrial aspiration smears, shows a high positive rate if ovarian cancer cells are observed in the abdominal cavity, cytology should be used as an important ancillary method for the assessment of ovarian cancer.     

The accuracy of endometrial cytology in the diagnosis of endometrial adenocarcinoma

tajima m., inamura m., nakamura m., sudo y. and yamagishi k. (1998) Cytopathology 9 , 369–380
The accuracy of endometrial cytology in the diagnosis of endometrial adenocarcinoma
We have examined 62 234 cytological samples of endometrium to establish the accuracy and false-positive rate for the diagnosis of endometrial adenocarcinoma. The patients were either attending the gynaecological out-patients clinic with symptoms or were asymptomatic women attending for routine population screening as part of our cancer detection programme, the numbers from these two sources being equal. Out of 138 cases identified as endometrial adenocarcinoma by cytology 126 (91.3%) were confirmed histologically in our hospital. Twelve cases (8.7%) were shown to be false-positives. Re-examination of these led to the same false-positive diagnosis in all 12 cases. This was attributable to similarities of nucleo–cytoplasmic ratio, irregular arrangement of nuclei, variation in nuclear shape and in the numbers of nucleoli in repair cells and hyperplastic cells compared with the carcinoma cases. Most of the false-negative reports were due to insufficient material, pale staining in malignant cells or diagnostic error. Refraction measurement of the density of nuclei of cancer cells using equipment for which the patent is pending enabled objective measurement of nuclear density which indicated that the nuclei were not stained darkly enough in false-negative cases.     

Diagnostic usefulness of endometrial aspiration cytology for endometrial cancer cases with normal curettage findings

OBJECTIVE: To determine whether endometrial aspiration cytology is useful for endometrial cancer cases with normal endometrial curettage findings. STUDY DESIGN: Eleven cases in which endometrial cancer could be detected by endometrial aspiration cytology but not endometrial curettage were classified into 2 groups by cancer locus, on the endometrial surface (A) or in the myometrium (B). A clinicopathologic and cytologic analysis was performed to compare the 2 groups. RESULTS: Five cases had cancer lesions localized at the fundus and one at the isthmus (group A). The other 5 had lesions localized in the myometrium (group B). The myometrium invasion was beyond half the myometrium in group B and within half in group A. It required > 2 cytologic examinations for a definitive diagnosis in 33.3% of group A and 80.0% of group B. The endometrial cytology differed clearly between the groups: large clusters of malignant cells with a dirty background (group A) vs. small clusters with a clean background (group B). The log-rank test revealed that group B had significantly poorer prognoses than did group A despite nearly the same rate of stage I/II cases in the 2 groups (p = 0.004). CONCLUSION: Endometrial aspiration cytology was useful for endometrial cancer cases with normal curettage findings as part of early detection. However, the cytologic diagnosis did not indicate good prognoses in the cases of cancer localized in the myometrium.     

Anatomic basis of endometrial cytology

A comparative cytologic and histologic study on 700 hysterectomy specimens showed that the cytologic evaluation of exfoliated cells from the uterine cavity did not correspond to the findings of the histologic examination of the endometrium in about 33% of sexually mature and 30% of postmenopausal women. The findings of both methods did not always coincide because the epithelial cells in the imprints or smears and the epithelial cells lining the glands in the histologic specimens belonged to structures that anatomically have little in common, one being superficial epithelium of the endometrium and the other being the glandular epithelium in the deep layers of the mucosa. This explains the false-negative results in the cytologic examination of the endometrium, especially in cases of glandular hyperplasia and early carcinoma, in which the foci of proliferation are initially covered by small and inactive surface epithelial cells and are inaccessible to cytologic investigation. False-positive cytologic results may occur in cases of irritated surface epithelium in chronic endometritis; this may also happen in women using an intrauterine device, during estrogen therapy, in regenerating mucosa after desquamation or curettage, in early pregnancy and after spontaneous abortion.     

Postpartum endometrial cytology in beef cows

The objectives were to characterize postpartum endometrial cytology and to determine the prevalence of subclinical endometrial inflammation and its impact on reproduction in beef cows. Samples for endometrial cytology (low-volume uterine lavage) were obtained from 135 of 137 Angus cows (2-87 d postpartum) in northern Minnesota, 26 d before breeding started. Agreement between examiners for subjective inflammation scores was very high (kappa = 0.971); the correlation between these scores and PMN counts was high (r = 0.83; P < 0.001), validating subjective categorization. The proportion of PMN and large mononuclear cells (principally macrophages) declined with postpartum interval (P < 0.001), whereas small mononuclear cells were consistently present (and not significantly affected by postpartum interval). Pregnancy rate to fixed-time AI was 29% and overall pregnancy rate was 89%. There was no association between cell type and ultimate pregnancy status or day of conception (P > 0.10). Although inflammation later in the postpartum period apparently impaired subsequent reproduction in dairy cows, in cows >50 d postpartum at sample collection in the present study, no cytological parameter significantly predicted final pregnancy status or day of conception. Previous twinning increased the risk of subclinical endometritis (P = 0.02), but not the probability of becoming pregnant (P = 0.14). In conclusion, we inferred that beef cows had the ability to clear uterine inflammation after resumption of ovarian cyclicity.     

Evaluation of pregnancy-related cells in endometrial cytology

OBJECTIVE: To determine the significance of pregnancy-related cells in endometrial smears. STUDY DESIGN: Pregnancy-related cells in 4429 endometrial smear samples were retrospectively analyzed and evaluated for clinicopathologic and cytomorphologic features. RESULTS: Of the 4429 endometrial smears taken for cancer screening, pregnancy-related cells were detected in 12 cases (0.3%). They were estimated cytologically as negative or suspicious and confirmed as cases ofspontaneous abortion (8 cases), placental site nodule (3 cases), and partial hydatidiform mole (1 case). Decidual cells were observed in all cases, and some of these showed atypia. Trophoblasts were observed in 5 (41.7%) of the 12 cases. Syncytiotrophoblasts were observed in 1 case (8.3%) and nonsyncytiotrophoblasts in 5 (41.7%) of the 12 cases. Pregnancy-related cells were observed in an endometrial smear in 7 cases; other cases were missed during cytologic examination and were retrospectively identified. CONCLUSION: Pregnancy-related cells are likely to be missed because they are difficult to identify or are surrounded by a cluster of endometrial cells. The decidual cell is a key cell for the cytologic diagnosis of pregnancy-related cells. Determining the existence of pregnancy-related cells in endometrial smears is important for the further assessment of patients and the differential diagnosis of several endometrial lesions.     

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.     

Post-breeding inflammation and endometrial cytology in mares

Endometritis has been reported to be the third most common medical condition of horses. Timely diagnosis and treatment of endometritis in mares increases the chance of pregnancy. Exfoliative endometrial cytology is often used as a clinical tool to evaluate endometrial inflammation through detection of neutrophils. There is a lack of information on the time frame for changes in endometrial cytologic parameters following breeding. The main objectives of this article are to use current information to describe systematic analysis of endometrial cytology using standardized methods for sample collection and interpretation, and discuss how these parameters change in relationship to post-breeding interval and mare susceptibility.     

Contribution of cervical cytology in the diagnostic work‐up of patients with endometrial cancer

Introduction

Abnormal cervical cytology in patients with endometrial cancer (EC) has been associated with poor outcome. The aim of this study was to evaluate whether cervical cytology could contribute to an improved preoperative identification of high‐grade EC (serous, clear cell, carcinosarcoma, high‐grade endometrioid EC) in final histology.

Methods

A retrospective cohort study was performed in five hospitals in the Netherlands. A total of 554 patients with EC that underwent primary surgical treatment between 2002 and 2010 were included. Primary outcome was defined as the contribution of abnormal cervical cytology in the preoperative identification of high‐grade EC. As secondary outcome, recurrence‐free survival (RFS) and disease‐specific survival were determined based on preoperative cervical cytology, and compared to the currently established risk factors: myometrial invasion, high‐grade and lymph vascular space invasion.

Results

Abnormal cervical cytology was present in 45.1%. For patients with preoperative inconclusive and high‐grade histology, the presence of abnormal cervical cytology contributed to an improved identification of high‐grade EC in final histology (odds ratio [OR] 6.40 [95% confidence interval {CI}: 1.92‐21.26]; OR 2.86 [95% CI: 1.14‐7.14]), respectively. Patients with abnormal cervical cytology had a significant worse 5‐year median RFS. Abnormal cervical cytology was independently related to RFS (hazard ratio 1.67 [95% CI: 1.04‐2.68]) and disease‐specific survival (hazard ratio 3.15 [95% CI: 1.74‐5.71]).

Conclusions

Abnormal cytology contributes to the preoperative identification of patients with high‐grade EC, and is associated with compromised outcome. Future studies are warranted to determine whether cervical cytology could be incorporated into preoperative prediction models for lymph node metastasis.     

The detection of endometrial tuberculosis in cases of infertility by uterine aspiration cytology

The cytology and histopathology of tuberculous endometritis are described in eight cases found among 200 women who presented with primary or secondary infertility. Because tuberculous endometritis is considered a possible cause of such sterility, the combination of endometrial aspiration and biopsy is recommended as an outpatient screening technique in such cases in areas where the rate of endometrial tuberculosis is high.     

Morphometric characterization of endometrial glands using quantitative cytology.

OBJECTIVE: To determine the usefulness of the combination of confocal laser scanning microscopy (CLSM), image cytometry and three-dimensional (3D) imaging for analyzing architectural changes indicative of endometrial hyperplasia and grade 1 adenocarcinoma. STUDY DESIGN: Papanicolaou-stained endometrial samples (n = 180) were analyzed for specific cellular characteristics and analyzed by CLSM. Confocal images were obtained and then analyzed cytometrically and used for 3D reconstruction. RESULTS: Values obtained after image cytometry and 3D imaging increased significantly (P < .01) with the degree of cellular atypia. CONCLUSION: The combination of CLSM, image cytometry and 3D imaging is a valuable method for differential diagnosis of endometrial hyperplasia and grade 1 adenocarcinoma.     

Diagnosing endometrial carcinoma with cervical involvement by cervical cytology

OBJECTIVE: To assess the relationship of a cervical cytologic diagnosis based on number, size and degeneration of malignant clusters and necrotic background to cervical involvement of endometrial carcinoma. STUDY DESIGN: Cervical smears of 53 women with endometrial carcinoma were evaluated for cervical involvement. The cytologic diagnosis was compared with actual involvement, and accuracy was calculated. Retrospectively, cytologic features, including number, size and degeneration of malignant clusters and necrotic background, were analyzed in involved and noninvolved cases. RESULTS: Cervical involvement was confirmed in 15 patients (28.3%). The number and size of malignant clusters in the involved cases were significantly larger than those in the noninvolved cases (P < .001 and < .01, respectively). The proportion of degenerated malignant cells and necrotic background in involved cases were significantly higher than those in noninvolved cases (P < .05). Cytologic diagnosis had a sensitivity and specificity of 62.5% and 86.8%, respectively. CONCLUSION: Cervical smears of involved cases revealed a large number and large size of malignant clusters. These findings support cytologic diagnosis based on number, size and degeneration of malignant cells and necrotic background. Cervical cytology is useful to exclude cervical involvement because of its high specificity and can help detect cervical involvement because of its moderately high sensitivity.     

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.