- Research article
- Open Access
- Open Peer Review
Three-dimensional ultrasonography and power Doppler for discrimination between benign and malignant endometrium in premenopausal women with abnormal uterine bleeding
© El-Sharkawy et al. 2016
- Received: 6 January 2015
- Accepted: 9 March 2016
- Published: 16 March 2016
Ultrasonography has been extensively used in women suspected of having a gynecological malignancy. The aim of this study is to evaluate the efficacy of 3D ultrasonography and power Doppler for discrimination between benign and malignant endometrium in premenopausal women with abnormal uterine bleeding.
This cross-sectional study included 78 premenopausal women with abnormal uterine bleeding scheduled for hysteroscopy and endometrial curettage. The endometrial thickness (ET), uterine artery pulsatility index (PI) and resistance index (RI), and endometrial volume (EV) and 3D power Doppler vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured and compared with hysteroscopic and histopathologic findings.
The ET (P <0.001), EV (P <0.001), and endometrial VI (P <0.001) and VFI (P = 0.043) were significantly increased in patients with atypical endometrial hyperplasia and endometrial carcinoma (n = 10) than those with benign endometrium (n = 68); whereas, the uterine artery PI and RI and endometrial FI were not significantly different between the two groups. The best marker for discrimination between benign and malignant endometrium was the VI with an area under the ROC curve of 0.88 at a cutoff value of 0.81 %.
3D ultrasonography and power Doppler, especially endometrial VI, may be useful for discrimination between benign and malignant endometrium in premenopausal women with abnormal uterine bleeding.
- 3D ultrasonography
- Endometrial carcinoma
- Premenopausal bleeding
Endometrial carcinoma is the most common form of gynecologic cancer in developed countries, and it is the fourth most common malignant tumor among women worldwide . Abnormal uterine bleeding is usually the first symptom; therefore, appropriate evaluation of women with premenopausal or postmenopausal bleeding will allow for early diagnosis of endometrial carcinoma and the best opportunity for cure .
Ultrasonography has been extensively used in women suspected of having a gynecological malignancy, especially in ovarian  and endometrial  cancer. In fact, transvaginal ultrasonography is considered the initial imaging procedure for evaluating abnormal vaginal bleeding due to its ability to depict endometrial pathology, its widespread availability, and its excellent safety profile and cost effectiveness .
Three-dimensional ultrasonography is a new imaging technique that has become currently available in gynecologic practice , specifically in gynecologic oncology . In addition, 3D power-Doppler ultrasonography allows a 3D reconstruction of the vascular network and also calculating vascular indices based on the total and relative amount of power Doppler information within the volume of interest .
The aim of this study is to evaluate the efficacy of 3D ultrasonography and power Doppler for discrimination between benign and malignant endometrium in premenopausal women with abnormal uterine bleeding.
This cross-sectional study was conducted at the Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, during the period from August 2013 to May 2014. The study protocol was approved by the Research Ethics Committee, and informed verbal consent was obtained from all participants.
The study population consisted of 78 premenopausal women with abnormal uterine bleeding scheduled for hysteroscopy and endometrial curettage. They were subjected to detailed history taking, complete general and gynecological examination, routine pre-operative laboratory investigations, and preliminary transvaginal ultrasound. The exclusion criteria included uterine fibroids, adenomyosis, endometrial polyps, and any general diseases, hormones or medications that could potentially affect pelvic blood flow.
Vascularization index (VI) measures the ratio of the number of color voxels to the total number of voxels (%) and represents the presence of blood vessels (vascularity). Flow index (FI) measures the mean power Doppler signal intensity (0–100) and represents the average intensity of blood flow. Vascularization flow index (VFI) is calculated by multiplying VI and FI (0–100) and represents a combination of vascularity and flow intensity.
Hysteroscopic examination was performed routinely before endometrial curettage using a rigid 30° hysteroscope and a 4-mm-diameter diagnostic sheath (Karl Storz GmbH & Co KG, Tuttlingen, Germany). The hysteroscopic diagnosis was based on the following criteria: atrophic endometrium-thin and homogeneous in appearance; endometrial hyperplasia-thickened endometrium, easily indented with pressure, with or without multipolyp appearance; and endometrial carcinoma-irregular growth with or without abnormal vascularization.
Endometrial sampling was carried out by formal dilatation and curettage. The histopathological samples were examined by two senior pathologists who determined the final diagnosis. Ultrasonographic findings were compared with hysteroscopic and histopathologic findings.
Data were expressed as mean ± SD or n (%) unless otherwise indicated. Continuous data were compared using Student t test or Mann-Whitney U test, as appropriate. Receiver-operating characteristic (ROC) curve analysis was used to evaluate the optimal cutoff value of ultrasound markers for prediction of malignant endometrial lesions; based on an equivalent sensitivity and specificity, and the highest value of the area under the curve (AUC). A P value <0.05 was considered statistically significant. The Statistical Package for the Social Science (SPSS Inc., Chicago, IL, USA), version 16.0, was used for data analyses.
Sample size calculation reveals that with a margin of error of 4.99 % and a response distribution of 50 %, the confidence level was 52 %; whereas with a margin of error of 9.92 % and a response distribution of 50 %, the confidence level was 84 %.
Patients’ characteristics and histopathological diagnosis (n = 78)
47.46 ± 2.94
4.18 ± 1.18
87.79 ± 11.49
157.10 ± 5.50
35.53 ± 2.09
Endometrial histopathology; n (%)
Characteristics of patients with benign and malignant endometrium
Benign (n = 68)
Malignant (n = 10)
46.88 ± 1.95
48.43 ± 2.99
4.18 ± 1.21
4.20 ± 1.03
87.76 ± 10.74
88.00 ± 16.44
157.38 ± 5.80
155.20 ± 1.81
35.29 ± 1.84
36.62 ± 8.42
7.615 ± 5.493
21.400 ± 9.489
Uterine artery PI
1.847 ± 0.638
2.080 ± 0.755
Uterine artery RI
1.140 ± 1.583
1.190 ± 0.796
3.410 ± 2.728
7.534 ± 3.622
Endometrial VI (%)
0.310 ± 0.418
1.005 ± 0.597
Endometrial FI (0–100)
22.897 ± 4.547
24.212 ± 9.562
Endometrial VFI (0–100)
0.100 ± 0.157
0.204 ± 0.072
Diagnostic performance of ultrasound markers
To the best of our knowledge and review of literature, this is the first study to evaluate the efficacy of 3D ultrasonography and power Doppler for discrimination between benign and malignant endometrium in women with premenopausal bleeding. Several previous studies have evaluated the role of 3D ultrasonography/power Doppler for the investigation of patients with postmenopausal bleeding.
Our results showed that the ET, EV, and endometrial VI and VFI were significantly increased in patients with malignant endometrium than those with benign endometrium; whereas, the uterine artery PI and RI and endometrial FI were not significantly different between the two groups. The best parameter for discrimination between benign and malignant endometrium was the VI with an AUC of 0.88 at a cutoff value of 0.81 %.
In agreement with our results, Mercé et al.  and Alcazar and Galvan  found that the flow indices were superior to EV for discrimination between endometrial carcinoma and endometrial hyperplasia, and between benign and malignant endometrium, respectively. The best predictor for endometrial cancer was VI. Odeh et al. , however, found that EV was superior to the flow indices for discrimination between hyperplasia/malignant endometrium and benign endometrium other than hyperplasia.
Epstein et al.  estimated the color content of the endometrium subjectively by choosing the most vascularized area and applying computer analysis to that area. They concluded that power Doppler analysis can contribute to a correct diagnosis of endometrial cancer in women with postmenopausal bleeding. Makled et al.  also concluded that 3D power Doppler measurements may be useful for distinguishing between benign endometrial lesions and endometrial carcinoma in women with postmenopausal bleeding.
Kurjak et al.  and Kupesic et al.  reported the use of volume measurements and power Doppler in diagnosing endometrial and adnexal malignancies; they found significant differences in the volume of malignant and benign lesions. They suggested that a combination of morphologic criteria and 3D power Doppler findings could identify endometrial lesions with sensitivity and specificity of 89 and 97 %, respectively.
Galván et al.  found that EV and VI were independently related to myometrial infiltration and tumor stage in endometrial carcinoma; VI was independently associated with tumor grade and EV correlated with lymph node metastases. Saarelainen et al.  also suggested that endometrial and, to a lesser degree, myometrial vascular indices and EV correlate with the depth of myometrial invasion in endometrial carcinoma.
Contrary to our results, Lieng et al.  did not find differences in 3D power Doppler indices between women with endometrial polyps and endometrial cancer before and after contrast enhanced examination. Opolskiene et al.  also concluded that, although 3D power Doppler indices were significantly higher in women with endometrial cancer as compared with those with benign pathology, the diagnostic performance of 3D ultrasound imaging was not superior to that of ET as measured by 2D ultrasound examination.
De Smet et al.  analyzed the correlation between EV and myometrial infiltration in a series of 97 women with endometrial cancer. They found that the predicted probability of deep myometrial infiltration increased when the ET increased, while this probability decreased when EV increased. This could be explained by non-linear effects.
The differences in results between our study and previous studies can almost certainly be explained by substantial differences in study populations and study design. There are differences in menopausal status, use of hormone replacement therapy, rate of endometrial cancer, and mix of benign histologies. There are also differences in the methods used to determine diagnostic performance of ultrasound markers. The relatively high rate of endometrial carcinoma and atypical hyperplasia in our study can be explained by exclusion of other causes of premenopausal bleeding in the study population.
Three-dimensional ultrasonography and power Doppler, especially endometrial VI, may be useful for discrimination between benign and malignant endometrium in premenopausal women with abnormal uterine bleeding before resorting to invasive procedures such as hysteroscopy and endometrial curettage. However, due to our relatively small sample size, further studies in larger series are needed to confirm these data.
- Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.View ArticlePubMedGoogle Scholar
- Sorosky JI. Endometrial cancer. Obstet Gynecol. 2008;111(2 Pt 1):436–47.View ArticlePubMedGoogle Scholar
- Mettler L. The cystic adnexal mass: patient selection, surgical techniques and long-term follow-up. Curr Opin Obstet Gynecol. 2001;13(4):389–97.View ArticlePubMedGoogle Scholar
- Clark TJ, Barton PM, Coomarasamy A, Gupta JK, Khan KS. Investigating postmenopausal bleeding for endometrial cancer: cost-effectiveness of initial diagnostic strategies. BJOG. 2006;113(5):502–10.View ArticlePubMedGoogle Scholar
- Dijkhuizen FP, Mol BW, Brölmann HA, Heintz AP. Cost-effectiveness of the use of transvaginal sonography in the evaluation of postmenopausal bleeding. Maturitas. 2003;45(4):275–82.View ArticlePubMedGoogle Scholar
- Bega G, Lev-Toaff AS, O’Kane P, Becker Jr E, Kurtz AB. Three-dimensional ultrasonography in gynecology: technical aspects and clinical applications. J Ultrasound Med. 2003;22(11):1249–69.View ArticlePubMedGoogle Scholar
- Alcázar JL, Jurado M. Three-dimensional ultrasound for assessing women with gynecological cancer: a systematic review. Gynecol Oncol. 2011;120(3):340–6.View ArticlePubMedGoogle Scholar
- Campbell S. Placental vasculature as visualized by 3D power Doppler angiography and 3D color Doppler imaging. Ultrasound Obstet Gynecol. 2007;30(6):917–20.View ArticlePubMedGoogle Scholar
- Mercé LT, Alcázar JL, Engels V, Troyano J, Bau S, Bajo JM. Endometrial volume and vascularity measurements by transvaginal three-dimensional ultrasonography and power Doppler angiography in stimulated and tumoral endometria: intraobserver reproducibility. Gynecol Oncol. 2006;100(3):544–50.View ArticlePubMedGoogle Scholar
- Alcazar JL, Galvan R. Three-dimensional power Doppler ultrasound scanning for the prediction of endometrial cancer in women with postmenopausal bleeding and thickened endometrium. Am J Obstet Gynecol. 2009;200(1):44. e1-6.View ArticlePubMedGoogle Scholar
- Odeh M, Vainerovsky I, Grinin V, Kais M, Ophir E, Bornstein J. Three-dimensional endometrial volume and 3-dimensional power Doppler analysis in predicting endometrial carcinoma and hyperplasia. Gynecol Oncol. 2007;106(2):348–53.View ArticlePubMedGoogle Scholar
- Epstein E, Skoog L, Isberg PE, De Smet F, De Moor B, Olofsson PA, Gudmundsson S, Valentin L. An algorithm including results of gray-scale and power Doppler ultrasound examination to predict endometrial malignancy in women with postmenopausal bleeding. Ultrasound Obstet Gynecol. 2002;20(4):370–6.Google Scholar
- Makled AK, Elmekkawi SF, El-Refaie TA, El-Sherbiny MA. Three-dimensional power Doppler and endometrial volume as predictors of malignancy in patients with postmenopausal bleeding. J Obstet Gynaecol Res. 2013;39(5):1045–51.View ArticlePubMedGoogle Scholar
- Kurjak A, Kupesic S, Sparac V, Bekavac I. Preoperative evaluation of pelvic tumors by Doppler and three-dimensional sonography. J Ultrasound Med. 2001;20(8):829–40.View ArticlePubMedGoogle Scholar
- Kupesic S, Kurjak A, Hajder E. Ultrasonic assessment of the postmenopausal uterus. Maturitas. 2002;41(4):255–67.View ArticlePubMedGoogle Scholar
- Galván R, Mercé L, Jurado M, Mínguez JA, López-García G, Alcázar JL. Three-dimensional power Doppler angiography in endometrial cancer: correlation with tumor characteristics. Ultrasound Obstet Gynecol. 2010;35(6):723–9.PubMedGoogle Scholar
- Saarelainen SK, Vuento MH, Kirkinen P, Mäenpää JU. Preoperative assessment of endometrial carcinoma by three-dimensional power Doppler angiography. Ultrasound Obstet Gynecol. 2012;39(4):466–72.View ArticlePubMedGoogle Scholar
- Lieng M, Qvigstad E, Dahl GF, Istre O. Flow differences between endometrial polyps and cancer: a prospective study using intravenous contrast-enhanced transvaginal color flow Doppler and three-dimensional power Doppler ultrasound. Ultrasound Obstet Gynecol. 2008;32(7):935–40.View ArticlePubMedGoogle Scholar
- Opolskiene G, Sladkevicius P, Jokubkiene L, Valentin L. Three-dimensional ultrasound imaging for discrimination between benign and malignant endometrium in women with postmenopausal bleeding and sonographic endometrial thickness of at least 4.5 mm. Ultrasound Obstet Gynecol. 2010;35(1):94–102.View ArticlePubMedGoogle Scholar
- De Smet F, De Brabanter J, Van den Bosch T, Pochet N, Amant F, Van Holsbeke C, Moerman P, De Moor B, Vergote I, Timmerman D. New models to predict depth of infiltration in endometrial carcinoma based on transvaginal sonography. Ultrasound Obstet Gynecol. 2006;27(6):664–71.Google Scholar