Endometrial carcinoma: the relevance of cervical cytology

In patients with endometrial carcinoma, preoperative identification of poor prognostic factors is helpful in planning therapy. Extended surgical staging, including pelvic and periaortic node dissection, is indicated in patients with deep myometrial invasion or high-grade tumor, or when other risk factors for extrauterine spread are present. In this study, cervical cytology was reviewed in 86 patients with endometrial carcinoma, all of whom underwent surgical staging, to correlate the cytologic results with surgical and pathologic findings. Cervical cytology was normal in 20 patients (23%), whereas suspicious or malignant endometrial cells were present in 23 and 43 cases (27 and 50%), respectively. Suspicious or malignant cervical cytology was associated with deeper myometrial invasion (P = .011), higher postoperative tumor grade (P = .006), positive peritoneal washings (P = .012), and more advanced stage by International Federation of Gynecology and Obstetrics criteria (P = .024). When compared with patients with normal cervical cytology, those who had malignant endometrial cells had over twice the risk of deep myometrial invasion (67 versus 30%), twice the risk of grade 2 or 3 tumor (60 versus 30%), and three times the risk of positive peritoneal washings (33 versus 10%). Seventy-four percent of patients with malignant cervical cytology were stage IC or more. In contrast, 70% of patients with normal cervical cytology were stage IA or IB. Patients with endometrial carcinoma who have malignant endometrial cells detected by cervical cytology are at increased risk of having a deeply invasive, high-grade, advanced-stage tumor, and therefore are more likely to require extended surgical staging.     

Preoperative assessment of myometrial and cervical invasion in endometrial carcinoma by transvaginal ultrasound

Objective

To evaluate the diagnostic accuracy of transvaginal ultrasound (TVS) in preoperative assessment of the depth of myometrial infiltration and the presence of cervical invasion in endometrial carcinoma.

Methods

298 consecutive patients with a diagnosis of endometrial cancer were evaluated by TVS within 3 days of surgical intervention. The depth of myometrial invasion was classified into two groups: no or < 50% invasion and ≥ 50% invasion. Invasion of cervix was diagnosed when the neoplastic tissue distended the cervix and showed ill-defined borders with the cervical stroma.

Results

The sensitivity, specifity, positive predictive value (PPV), negative predictive value (NPV) and overall diagnostic accuracy of TVS in evaluation of the depth of myometrial infiltration were 68.4%, 82%, 65.1%, 84.1% and 77.5%, respectively. While the sensitivity and PPV were significantly higher among grade 3 tumors, the specifity, NPV and accuracy were significantly higher among grade 1 tumors.The sensitivity, specifity, PPV, NPV, and overall diagnostic accuracy of TVS in assessment of the presence or absence of neoplastic tissue in cervix were 76.5%, 99.3%, 86.7%, 98.2% and 98%, respectively. While the sensitivity and PPV were significantly higher among grade 1 tumors, the NPV and accuracy were significantly lower among grade 3 tumors.

Conclusion

TVS can be considered as a feasible, economical and simple imaging modality with a high diagnostic accuracy for the prediction of cervical involvement. However, it is not a reliable method in estimating the depth of myometrial infiltration.     

Classification of endometrial cells on cervical cytology

One hundred eighty-eight women who had endometrial cells on cervical cytologic specimens during the secretory phase or in the postmenopausal period were studied retrospectively. Each had undergone hysterectomy or endometrial biopsy within 12 months of the original smear. The endometrial cells were classified as typical, atypical, or suspicious for carcinoma. Among premenopausal subjects, three of 57 with typical cells had endometrial hyperplasia, one of two with atypical cells had endometrial polyps, and both with cells suspicious for carcinoma had endometrial carcinoma. In the postmenopausal group, ten (13.5%) of 74 with typical endometrial cells had either hyperplasia or carcinoma, and five (22.7%) of 22 with atypical cells and 24 77.4%) of 31 patients with suspicious cells had either hyperplasia or carcinoma. The present findings and a review of the pertinent literature demonstrate that the classification system used is helpful in predicting the risk for endometrial disease in patients with endometrial cells seen on cervical cytologic smears during the secretory phase or in the postmenopausal period.     

Peritoneal cytology in patients with endometrial carcinoma

Peritoneal cytology was obtained in 61 patients with carcinoma of the endometrium at the time of laparotomy. The incidence of positive peritoneal cytology was 23.0%. It increased as the clinical stage advanced. The incidence of positive peritoneal cytology in patients with well-differentiated carcinoma or superficial myometrial invasion was low. The rate of paraaortic lymph node metastasis was higher in patients with positive peritoneal cytology than in patients with negative peritoneal cytology. However, this trend was not recognized in pelvic lymph node metastasis. In the positive peritoneal cytology group, 64.3% had disease outside of the uterus, while in the negative group only 12.8%. The 2-year survival rate in patients with positive peritoneal cytology was 57.1% and it was 86.4% in patients with negative peritoneal cytology. It is concluded that the findings of positive peritoneal cytology is an important prognostic factor and routine peritoneal cytology should be obtained at the time of laparotomy in patients with carcinoma of the endometrium.     

Preoperative hysteroscopic assessment of cervical invasion by endometrial carcinoma: a retrospective study

OBJECTIVE: The aim of this study was to evaluate the efficacy of hysteroscopy, using normal saline (NS) or carbon dioxide (CO2) as the distention medium, in assessing tumor invasion of the uterine cervix by endometrial carcinoma. METHODS: A retrospective study was conducted in 200 consecutive patients with endometrial carcinoma diagnosed from 1993 to 2000. Prior to definitive surgical treatment, hysteroscopy was performed using either NS or CO2 as the distention medium to determine whether the tumor had spread to the cervix. The uterine specimens obtained after hysterectomies were cut open for gross examination. Tumor invasion of the cervix as determined by hysteroscopy and gross examinations was compared with the pathological findings. RESULTS: Tumor invasion of the cervix was found in 41 (20.5%) cases on pathological examination. Hysteroscopy has an accuracy of 92.5% (185/200), a sensitivity of 68.3% (28/41), and a specificity of 98.7% (157/159), with a PPV of 93.3% (28/30) and a NPV of 92.4% (157/170) in determining cervical involvement. Assessment by gross inspection had 93.0% (186/200) accuracy, 68.3% (28/41) sensitivity, 99.4% (158/159) specificity, 96.6% (28/29) PPV, and 92.4% (158/171) NPV. There was no significant difference between the two assessment methods. When the results of hysteroscopy performed with different distention mediums were compared, the use of NS had a higher accuracy in determining tumor spread to the cervix (96.8% vs 88.7%, P = 0.03) and NPV (96.4% vs 88.4%, P < 0.05) than the use of CO2. CONCLUSIONS: Hysteroscopic assessment and gross examination of the uterine specimen had similar efficacy in detecting cervical invasion by endometrial carcinoma. Hysteroscopic examination using NS is more accurate than that which uses CO2.     

Preoperative radiotherapy for early endometrial carcinoma

A retrospective study was undertaken to compare the use of one versus two preoperative radium systems for early endometrial carcinoma. The charts of 73 patients treated between 1977 and 1980 were reviewed. No difference was noted between the two groups when compared for stage, grade, depth of myometrial invasion, and histologic type of tumor. One of thirty-eight (2.6%) patients in the one-radium group developed an isolated central recurrence; there were no central recurrences in the two-radium group. Total duration of therapy and total hospitalization for the one-radium versus the two-radium group were 17.6 and 15.3 days versus 77.0 and 17.3 days, respectively. Follow-up ranged from 48 to 84 months. Corrected survival figures are comparable to 94.6% for the one-radium group versus 100% for the two-radium group. These data suggest comparable effectiveness and morbidity between the two treatment regimens, with the single-radium application more efficient and cost effective.     

子宫内膜癌腹腔洗液细胞学检查与预后

目的 探讨腹腔洗液细胞学检查在评价子宫内膜癌患者预后中的价值。方法 对1992年1月～2000年1月我院收治临床分期Ⅰ-Ⅱ期的113例子宫内膜癌患者进行回顾分析及随访。结果 113例子宫内膜癌患者中,腹腔洗液细胞学检查阳性者23例(20.4％),其中4例(17.4％)死于术后复发;90例阴性的患者中,13例(12.56％)死于术后复发,Cox回归分析显示腹腔洗液细胞学检查结果与子宫内膜癌预后相关无显著性(P=0.9516);23例阳性患者中,6例(26％)为不良病理类型,9例(39％)有深肌层浸润,5例(21.7％)宫颈受累,5例(21.7％)有淋巴结转移,Logistic回归多因素分析表明与腹腔洗液细胞学检查阳性有显著相关(P<0.05)。结论 腹腔洗液细胞学检查不能独立作为评价子宫内膜癌患者预后的指标。与腹腔洗液细胞学检查阳性有关的高危因素有不良病理类型、深肌层浸润、宫颈受累和淋巴结转移。     

Prognostic value of peritoneal cytology in endometrial carcinoma

To determine whether positive peritoneal cytology is an independent poor prognostic factor in patients with endometrial carcinoma the records of 381 patients were reviewed. Positive peritoneal cytology was found in 24 of 381 (6.3%) patients. In clinical stage I disease, 16 of 322 (5.0%) patients had positive peritoneal cytology. Patients with positive cytology were more likely to have higher-grade tumors and extrauterine disease at the time of surgery (45% vs 2.3%) than were patients with negative cytology. Five-year survival was significantly less for patients with positive cytology than negative (50% vs 81.2%). For patients with surgical stage I disease (no extrauterine spread at surgery) there was no significant difference in 5-year survival between groups with positive and negative cytology (80% vs 86.3%). The majority (70.8%) of patients with endometrial cancer and positive peritoneal cytology have extrauterine disease at the time of surgery. Although overall 5-year survival is less for patients with positive cytology, when other risk factors are controlled for, there is no difference in survival for patients with no demonstrable extrauterine disease despite positive cytology. We conclude that positive peritoneal cytology is not an independent prognostic indicator for patients with endometrial cancer.     

Significance of normal endometrial cells detected by cervical cytology

A retrospective study was conducted to assess and confirm the significance of normal-appearing endometrial cells detected in cervical cytologic smears in the second half of the menstrual cycle or in the postmenopausal period. Of 440 women with normal endometrial cells identified on routine Papanicolaou smears, 179 underwent further endometrial evaluation. Endometrial disease was identified in 64 (35.7%) of those patients having endometrial sampling and/or hysterectomy within 12 months of the cytologic evaluations. These lesions included 21 cases (11.7%) of endometrial polyps, 23 cases (12.9%) of endometrial hyperplasia, and 20 cases (11.2%) of adenocarcinoma. The frequency of endometrial cancer was positively associated with age (P less than .01). Five of 20 women with endometrial cancer were asymptomatic.     

Significance of atypical endometrial cells detected by cervical cytology

A retrospective study was conducted to assess the histologic significance of atypical endometrial cells identified on routine cervical cytology. One hundred seventy-seven women had Papanicolaou smears demonstrating atypical endometrial cells. The histology of the endometrium was available from endometrial sampling and/or hysterectomy in 134 of the patients within 12 months of their abnormal cytologic evaluation. Fifty-six women (42%) had endometrial disease, including 14 cases (10%) of endometrial polyp, 15 cases (11%) of endometrial hyperplasia, and 27 cases (20%) of adenocarcinoma. The frequency and nature of the endometrial changes depended on the age of the patient (P less than .001) and the degree of cytologic atypia (P less than .05). In 21 women over 59 years who had atypical endometrial cells suspicious for adenocarcinoma, 12 (57%) had adenocarcinoma. Using this information, we have estimated the risk of adenocarcinoma in various groups of women with atypical endometrial cells.     

Prognostic significance of positive peritoneal cytology in endometrial carcinoma

A retrospective review of 280 patients with endometrial carcinoma who had peritoneal cytologic examination done at the time of laparotomy was undertaken. A positive cytologic finding was the only manifestation of extrauterine disease in 16 patients (6%). Four (25%) of these patients had a recurrence. Only 13 (5%) of 237 patients with negative cytologic findings had a recurrence. Positive peritoneal cytology is a marker for potential recurrence.     

Peritoneal cytology as a prognostic indicator in endometrial carcinoma

Among the prognostic indicators of endometrial carcinoma, the presence of cancer cells in peritoneal washings has been suggested as indicating a poor prognosis. This proposition was examined for 373 patients; positive peritoneal washings were observed in 20 of 335 patients with stage I disease and 10 of 29 with stages II-IV. In 13 of the 30 patients there was no gross evidence of disease. Within a follow-up period of two years, positive cytology appeared to be a sign of poor prognosis.     

C-kit immunoreactivity in endometrial adenocarcinomas and its clinicopathologic significance.

The proto-oncogene c-kit is a transmembrane-tyrosine-kinase receptor that is structurally related to the platelet-derived growth-factor receptor (PDGFR) and is involved in cell differentiation. C-kit has been found to be expressed in certain solid tumors and may play a role in their tumorigenesis. Recently, a tyrosine-kinase inhibitor specific for the PDGFR family, bcr-abl, and c-kit (STI571) has been reported to have therapeutic effects in tumors expressing the aberrant forms or high quantities of target proteins. Expression of c-kit has not been well evaluated in endometrial adenocarcinomas. In this study, c-kit immunoreactivity was evaluated on paraffin sections of 72 endometrial adenocarcinomas (57 endometrioid, 10 serous, and 5 clear cell) with a polyclonal antibody. Immunoreactivity of c-kit was analyzed semiquantitatively and correlated with various clinicopathologic factors. Cytoplasmic c-kit immunoreactivity was detected in 42 (58%) tumors. Thirty-four (60%) endometrioid, 8 (80%) serous, and 0 of the 5 clear-cell adenocarcinomas were c-kit positive. There was a significant correlation between c-kit positivity and the depth of myometrial invasion. Patients with c-kit-positive endometrial adenocarcinomas more frequently had metastases and shorter disease-free survival. Expression of c-kit may be a potentially adverse prognostic feature in endometrial adenocarcinoma. Patients with c-kit-positive advanced endometrial adenocarcinoma might benefit from tyrosine-kinase-inhibitor therapy.     

Cyclooxygenase-2 expression in cervical intraepithelial neoplasia III and squamous cell cervical carcinoma, and its correlation with clinicopathologic variables

The objective of the study was to compare cyclooxygenase-2 (COX-2) expression in cervical intraepithelial neoplasia III (CIN III) and squamous cell carcinoma (SCC) of the cervix, and its correlation with clinicopathologic factors of SCC with a review of the available literature. This study included 25 patients with CIN III and 67 patients with stage I-IIa SCC. All patients in the SCC group were treated with radical hysterectomy plus pelvic and para-aortic lymphadenectomy and postoperative chemoradiotherapy based on their histopathologic risk factors. Immunohistochemical analysis was performed on paraffin-embedded sections with COX-2 antibody. COX-2 expression in the SCC group was significantly higher than in the CIN III group (55.2% [37/67] vs 24% [6/25]; P= 0.008). Significantly higher expression of COX-2 was observed in patients with lymphovascular space invasion (LVSI) compared to patients without LVSI (61.9% [34/55] vs 33.3% [3/9]; P= 0.02). Additionally, patients with tumor sizes >4 cm had significantly higher COX-2 expression than patients with tumor sizes <4 cm (65.9% [27/41] vs 39% [10/26] P= 0.028). There was no significant relationship with respect to COX-2 expression and parametrial involvement, lymph node metastasis, recurrences, and survival. In multivariate analysis, LVSI was the only statistically significant determinant for COX-2 expression (P= 0.024; OR = 2.35; 95% CI = 1.1-4.9). Our results and a review of the literature both suggest that COX-2 expression may have a role in the development and progression of CIN III and it is related to some clinicopathologic variables of cervical carcinoma. Further studies are needed to clarify the role of COX-2 inhibitors in the management of CIN and SCC.     

Angiogenesis in endometrial carcinoma: correlation with survival and clinicopathologic risk factors

Association among angiogenesis, survival and clinicopathologic parameters in endometrial carcinoma was evaluated. Sixty patients who had been diagnosed as endometrial carcinoma, from 1993 to 1998, were included in the study. All patients had been surgically staged with bilateral pelvic and para-aortic lymph node dissection. All hysterectomy specimens were stained immunohistologically for factor VIII-related antigen. The area with the most intensified microvasculature was determined under low-power (x100) magnification, and the microvessel count of this area under high-power (x200) magnification was determined as the microvessel density (MVD) of the tumor. The mean MVD was 26.2 +/- 13.0 (range 6-68), and it was considered as high (n = 24; 40%), moderate (n = 19; 31.7%) and low (n = 17; 28.3%) when the MVD was >30, between 15-30 and <15, respectively. Statistical analysis included Mann-Whitney, Kruskal-Wallis and Spearman rank correlation tests. The Kaplan-Meier method was used to evaluate the difference between angiogenesis and survival. Multivariate analysis with the Cox regression model was used in MVD values and different clinicopathological parameters. There was positive correlation between MVD increase and surgicopathological stage (p < 0.05). A significant difference was seen between MVD increase and lymph node metastasis (p < 0.05). There were no differences between MVD and age, histological type, grade and lymphovascular invasion. MVD did not change in association with myometrial invasion depth. There was a significant difference in means of survival between the low and high MVD groups (p = 0.01). However, MVD was not an independent prognostic factor in multivariate analysis. Increased angiogenesis was found to be associated with advanced stage and decreased survival in endometrial carcinoma.     

Preoperative radiation therapy in clinical stage II endometrial carcinoma.

From 1980 to 1987, 30 patients with FIGO clinical Stage II carcinoma of the endometrium were treated with 5000 cGy preoperative pelvic radiation therapy at Thomas Jefferson University Hospital. Patients with gross cervical disease received additional intracavitary irradiation with a tandem and ovoids for a combined total dose of 7000 cGy to point A. All patients then underwent exploratory laparotomy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH/BSO). The 5-year actuarial survival for the entire group was 69%. The 5-year actuarial survival for the 8 patients with papillary serous, clear cell, and undifferentiated small cell carcinoma was 38%, with most patients failing in the upper abdomen. The 5-year actuarial survival for the remaining 22 patients was 82%. The only local failure occurred in the patient with an undifferentiated small cell carcinoma. Although preoperative pelvic radiation therapy together with TAH/BSO appears to offer excellent local control in all patients with Stage II endometrial carcinoma, additional treatment options should be considered for patients with papillary serous and clear cell histologies because of the poor survival and high failure rate in the upper abdomen.