Blood Flow in Functional Cysts and Benign Ovarian Neoplasms in Premenopausal Women

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1 Blood Flow in Functional Cysts and Benign Ovarian Neoplasms in Premenopausal Women Juan Luis Alcazar, MD, Tania Errasti, MD, Matias Jurado, MD To assess the value of transvaginal calor Doppler sonography in the differentiation of functional cysts from benign ovarian neoplasms in premenopausal women, 100 premenopausal women with the diagnosis of adnexal mass were enrolled in a prosfective study. All patients underwent transvagina calor Doppler sonography during the follicular phase. We evaluated 107 masses. Tumor volume and morphology were assessed, as were tumor blood flow location, the number of vessels, the resistive and pulsatility indices, and the peak systolic velocity. Patients were followed up after 8 to 10 weeks by transvaginal sonography. Functional cysts were considered when spontaneous resolution occurred. Surgery was performed if a tumor enlarged or persisted after two scans. Thirty-nine (36.5%) cysts regressed spontaneously and 68 (63.5%) were removed surgically. Seven of the latter were follicular or luteal cysts and were considered to be functional cysts. No carcinoma was found. Arterial blood flow was detected in 28 (60.8%) functional cysts and in 42 ABBREVIATIONS CV!, Calor velocity imaging; FVW, Aow velocity waveform; RI, Resistive index; PI, Pulsatility index; S, Systolic; D, Diastolic; PSV, Peak systolic velocity; SD, Standard deviation; Cl, Confidence interval Received February 21, 1997, from the Department of Obstetrics and Gynecology, Clinica Universitaria de Navarra, University of Navarre, School of Medicine, Pamplona, Spain. Revised manuscript accepted for publication August 12, Address correspondence and reprint requests to Juan Luis Alcazar, MD, Department of Obstetrics and Gynecology, Clinica Universitaria de Navarra, Avenida Pio XII, 36, Pamplona, Spain. (68.8%) benign neoplasms (P: ). The vessels were located peripherally in 27 (94.6%) functional cysts and in 37 (88.1 %) benign neoplasms (P :: ). No differences were found between functional cysts and benign neoplasms in mean resistive index (0.65, 95% confidence interval: 0.59 to 0.71 versus 0.64, 95% confidence interval: 0.60 to 0.69), mean pulsatility index (1.47, 95% confidence interval: 1.17 to 1.84 versus 1.57, 95% confidence interval: 1.26 to 1.86), number of vessels (1.1, 95% confidence interval: 0.7 to 1.3 versus 1.4, 95% confidence interval: 1.1 to 1.8), and peak systolic velocity (28.6 cm/s, 95% confidence interval: 24.7 to 34.2 versus 24.9 cm/s, 95% confidence interval: 21.6 to 28.3). We concluded that transvaginal calor Doppler sonography is not useful to discriminate between functional ovarian cysts and benign ovarian neoplasms in premenopausal women. KEY WORDS: Transvaginal calor Doppler sonography; Premenopausal women; Functional ovarian cysts; Cysts, ovarian; Ovary, benign neoplasms. T he management of an adnexal mass in women of reproductive age remains a common clinical gynecologic problem. Most of these cysts are functional ovarian cysts, which are either follicular cysts that result from a failure of the follicle to rupture or regress or corpus luteum cysts that derive from a failure to regress in a nonpregnant patient.l The incidence of hospitalization for functional ovarian cysts has been estimated to be as high as 500 per 100,000 women per year in the United States.2 Furthermore, it has been reported that approximately up to 66% of young women operated on for ovarian enlargement had a postoperative 1997 by the American Institute of Ultrasound in Medicine J Ultrasound Med 16: , /97/$3.50

2 820 BLOOD FLOW IN FUNCTIONAL CYSTS J Ultrasound Med 16: histopathologic diagnosis of follicular or luteal cysts.l A correct diagnosis therefore could avoid many unnecessary surgical interventions in young women. The diagnosis of a cystic adnexal mass in premenopausal women frequently is a casual finding on ultrasonographic examination in otherwise asymtr tomatic patients. In these cases, the differential diagnosis between ovarian neoplasm and functional ovarian cysts should be considered. The typical sonogmphic appearance of a functional ovarian cyst is a clear thin-walled and smooth-walled cyst, usually without septa or papiljary projections.~ More complex appearances can sometimes be found, especi<dly in cases of luteal cyst. ~ However, this typical morphology is not specific and similar sonographic characteristics may be found in benign ovarian neoplasms, such as serous cystadenomas.~ Recently, with the introduction of transvaginal color Doppler ultrasonography, the assessment of tumor vascularization has become feasible.s This technique has been widely used in the differentiation of malignant from benign ovarian tumors, with con troversial results.s-w However, to the best of our knowledge, only one study has been reported evaluating the usefulness of this technique in differential ing functional ovarian cysts from benign ovarian neoplasms. n In the present study we aimed to evaluate whether the assessment of tumor blood flow could help differentiate between functional ovarian cysts and benign ovarian neoplasms in premenopausal women. MATERIALS AND METHODS Between January 1995 and October 1996, 100 premenopausal women with the diagnosis of adnexal mass were enrolled in a prospective study. Only patients with a mean tumor diameter of greater than 3 cm were included. No patient who had recently received treatment for ovulation induction was included, as these patients were at higher risk of developing functional ovarian cysts. All patients were evaluated during the follicular phase of the menstrual cycle by transvaginal ultrasonography using a Philips P-700 SE (Philips Ultrasound, Santa Ana, CA) with a real-time 6.5 MHz sector electronic array endovaginal probe with 5 MHz pulsed Doppler probe and equipped with the CVI system for color blood flow codification. The high-pass filter was set at 100Hz in every case. Pulsed Doppler sample volume was set at 1.2 mm width. The system operates at power outputs of less than 80 m W I cm2 in the B-mode, pulsed Doppler mode, and CVI mode. A thorough morphologic evaluation of the adnexal mass was performed in each case. Ovarian masses were classified as unilocular smooth-walled dear cyst, unilocular smooth-walled cyst with internal echoes, multilocular cyst, cystic-solid mass, or solid mass. Tumor volume was calculated by using the formula of the prolate ellipsoid (Vol = 01 x 02 x 03 x ), where 01, 02, and 03 were the diameters of the three orthogonal planes measured in centimeters. Volume was expressed in milliliters. After morphological evaluation was done, the CVI gate was activated for color imaging of blood flow. When color signals were detected within a given tumor they were counted and localized. The location of tumor vessels was stated as peripheral (within the cyst's wall, at the base of septa or papillae) or central (solid areas, septa or papillae). Then the pulsed Doppler probe was used to interrogate each color signal detected and a FVW was obtained in each case. Only arterial FVW were analyzed. The RI and PI values were calculated from three consecutive cardiac cycles, according to the following formulae: RI = (S - D)/ 5, and PI = (S - 0)/ M, where S is the peak systolic velocity, D is the end-diastolic velocity, and M is the mean flow velocity. Maximum PSV was recorded in each vessel. In those cases in which more than one artery was found within the Sc:1me tumor the lowest RI and PI detected were used for analysis. A tumor was considered as having no flow when no vessel could be detected after 15 min. All of the women were offered follow-up examination at 8 to 10 weeks' interval, always during the follicular phase. If the ovarian mass was not found on the follow-up scan, it was considered to have been a functional ovarian cyst with spontaneous resolution. Surgery was performed on the patient's own decision or if the mass persisted or enlarged after two consecutive scans. Definitive histopathologic diagnosis was obtained in all cases in which operation was performed. All examinations were performed by one of the authors (J.L.A.). Intraobserver variability was estimated by calculating the coefficient of variation in three consecutive examinations at 10 min intervals in the first 20 patients included in the study. The coefficients of variation for PSV, RI, PI, and number of vessels per tumor were 8%, 6.5%, 10%, and 4 ~, respectively. The data are expressed as mean and SD; 95% Cl values were calculated where appropriate.

3 J Ultrasound Med 16: ALCAZAR ET AL 821 Comparison of continuous data was performed by using one-way analysis of variance. Comparison of categorical data was performed by using the cmsquare test. A P value of less than 0.05 was considered statistically significant. Statistical calculations were performed using the SPSS 6.0 statistical package (SPSS, Chicago, IL). RESULTS A total of loo patients were included in this study. Seven patients had bilateral masses, giving a total of 107 masses evaluated. All patients were white. No patient was taking oral contraceptives at the time of the study. During the study period 39 (36.5'V..) ovarian masses resolved spontaneously and were considered to be functional cysts. Sixty-eight (63.5'..) masses in 61 patients were removed surgically. Histopathologic analysis revealed benign tumors in all cases, with the following diagnoses: endometriomas (26 cases), serous cystadenoma (11 cases), hemorrhagic cyst (nine cases), follicular cyst (six cases), mature teratoma (five cases), tubo-ovarian abscess (three cases), mucinous cystadenoma (two cases), parovarian cyst (one case), ovarian fibroma (one case), benign granulosa cell turner (one case), luteal cyst (one case), cystadenofibroma (one case), and hydrosalpinx (one case). The six follicular cysts and the luteal cyst were considered functional cysts for analysis, giving a total of 46 functional cysts. The mean age of the patients with functional ovarian cysts was 39.9 years (range, 16 to 55 years; SO, 9.6 years) and of the patients with ovarian neoplasms was 36.1 years (range, 19 to 50 years; SO, 9.6 years) (P > 0.05). On ultrasonographic examination most functional ovarian cysts were unilocular, clear, and smoothwalled cysts (Table 1) (Figs. 1, 2). Mean tumor volume in functional cysts (47.7 ml; 95% Cl, 33.2 to 64.4) was significantly lower than in patients with benign neoplasms (90.4 ml; 95% Cl, 67.9 to 112.9) (P = ). Arterial blood flow was detected in 28 (60.8%) functional cysts and 42 (68.8%) benign neoplasms (chi-square = 1.24, P = ) (Figs. 3, 4). Vessels were located peripherally in 27 (94.6%) functional cysts and in 37 (88.1%) benign neoplasms (chi-square = 1.49, p = ). No differences were found between functional ovarian cysts and benign ovarian neoplasms in the number of vessels per tumor, PSV, RI, or PI (Table 2). DISCUSSION The management of the adnexal cyst in premenopausal women remains a common clinical problem. It is widely accepted that most of these cysts are functional ovarian cysts. In a recent prospective study in a large series of adnexal tumors in young women, Osmers and coworkers found that 53.2'}1. of all masses detected were functional ovarian cysts.j2 When an adnexal mass is diagnosed in a women of reproductive age, conservative management with follow-up scans usually is recommended because of the knowledge that most cysts will regress spontaneously.ll In the case of presumed functional ovarian cysts, some authors have advocated the used of oral contraceptives.t~. 1 s: However, it has been demonstrated that a similar rate of successful resolution of these cysts can be achieved with expectant management.ln,17 Osmers and coworkers showed that 89% of functional cysts regressed spontaneously during followup.12 Our results are similar, with a spontaneous resolution rate of 84%. Nevertheless, despite these two therapeutic alternatives, it has been estimated that about 15'., of functional cyst will ultimately be removed surgically.ls Indeed, at the initial ultrasonographic scan the differential diagnosis of functional ovarian cysts and other ovarian neoplasms is difficult, especially in those patients who have not recently undergone ovulation induction or in perimenopausal patients, who have an increased prevalence of ovulation disorders. The typical sonographic appearance of a functional cyst is a sonolucent thin-walled and smooth-walled Table 1: Sonographic Characteristics of Ovarian Cysts Smooth-Walled Cyst Unilocular Clear Internal Echoes Unilocular Cyst with Multiocular Cystic-solid Cyst Mass Functional cyst Benign neoplasms Total Chi-squilre: 39.5, P <

4 822 BLOOD FLOW IN FUNCTIONAL CYSTS J Ultrasound Med 16: Figure 1 Typical sonographic appearance of a functional cyst as a round, smooth-walled hypoechoic Jesion. Figure 2 Sonographic appearance of a dear, thin-walled, and smooth walled cyst, correspond ing to a serous cystadenoma. However, this appearance is not spedfic.4.1:! The existence of a technique that could differentiate functional cysts from ovarian neoplasms would be valuable, as it would allow prediction of which cases would undergo spontaneous resolution of the cyst and thus avoid unnecessary surgical interventions. With the introduction of transvaginal color Doppler ultrasonography the assessment of adnexal tumor vascularization has become feasible.l9 Several studies have been performed using this technique to differentiate benign from malignant adnexal masses/ 111 among them one study performed to evaluate the role of transvaginal color Doppler sonography in the differentiation between functional ovarian cysts and benign ovarian neoplasms.l Fleischer and colleaguesll evaluated 64 adnexal masses prospectively and serially at 3 week intervals for up to 12 weeks. They found that 75% of masses regressed spontaneously. Most adnexal masses that underwent spontaneous resolution had a cystic appearance on sonographic examination, were found in younger women, and had a lower mean size than those that did not regress spontaneously. These results are similar to our findings. Flejscher and associates concluded that serial transvaginal calor Doppler sonography may distinguish those patients who require surgical intervention from those who might be managed conservatively, a conclusion that was based on their findings that most masses that regressed spontaneously (72%) had a high PI on initial Doppler examination and showed a progressive increase of PI on serial scans. These authors detected blood flow in all so-called functional cysts. The blood flow detection rate in functional cysts is our study (60.8%) is higher than that reported by Kurjak and Kupesic (18.6%)10 and Tekay and Jouppila (28%).6 Furthermore, it was as high as the blood flow detection rate in benign ovarian tumors (68.8%). This could be explained by the fact that functional cysts usually developed in otherwise normal ovaries, and blood flow could be detected from ovarian vessels feeding the functional cyst, usually in its periphery, within the ovarian stroma. In fact, a similar blood flow detection rate in normal ovaries and benign ovarian tumors in premenopausal women has been reported,2l On the other hand, we found no differences in the RI, PI, or PSV in our series. In fact, in our series all cyst.,~ Figure 3 Transvaginal color Doppler sonogram of a socalled functional cyst shows peripheral vessels with high impedance.

5 J Ultrasound Med 16: ALCAZAR ET AL REFERENCES DiSaia PJ: Ovarian neoplasms. In Scott JR, DiSaia PJ, Hammond CB, et al (Eds): Danforth's Obstetrics and Gynecology. 7th Ed. Philadelphia, JB Lippincott, 1994, p969 Crimes DA, Hughes JM: Use of multiphase oral contraceptives and hospitalizations of women with functional ovarian cysts in the United States. Obstet Gynecol 73:1037, Eriksson L, Kjellgren 0, von Schoultz B: Functional cyst or ovarian cancer: Histopathological findings during one year surgery. Gynecol Obstet Invest 19:155, Sutton CL, McKinney CD, Jones JE, et a!: Ovarian masses revisited: Radiologic and pathologic correlation. RadioGraphies 12:853, 1992 Figure 4 Transvaginal color Doppler sonogram of an ovarian tumor shows blood flow within a septum. The definitive histopathologic diagnosis was ovarian mucinous cystadenoma. 5. Kurjak A, Zalud I, Alfirevic Z: Evaluation of adnexal masses with transvaginal color Doppler ultrasound. J Ultrasound Med 10:295, Tekay A, Jouppila P: Validity of pulsatility and resistance indices in classification of adnexal tumors with transvaginal color Doppler ultrasound. Ultrasound Obstet Gynecol 2:338, 1992 functional cysts had high impedance (PI > 1.0) on initial Doppler examination, but this also was found in benign tumors. This could be explained by the fact that angiogenesis in benign tumors and functional cysts in the follicular phase is limited, and the arterial supply is derived from preexistent ovarian vessels in both types of cysts. We did not assess tumor vascularization serially. Thus, we cannot compare results on serial Doppler assessment of adnexal tumors. Nevertheless, our results indicate that tumor blood flow assessment on initial scan is not useful to discriminate functional ovarian cysts from benign ovarian neoplasms. Therefore, serial ultrasonographic scans remain as the best approach to detect func tional cysts. 7. Weiner Z, Thaler I, Beck D, et al: Differentiating malignant from benign ovarian tumors with transvaginal color flow imaging. Obstet Gynecol79:159, Valentin L, Sladkevicius P, Marsal K: Limited contribution of Doppler velocimetry to the differential diagnosis of extrauterine pelvic tumors. Obstet Gynecol 83:425, 1994 Prompeler HJ, Madjar H, Sauerbrei W: Classification of adnexal tumors by transvaginal color Doppler. Gynecol Oncol 61:354, 1996 Table 2: Doppler Sonographic Characteristics of Functional Cysts and Benign Neoplasms RJ Functional cysts PSV No. of vessels ( ) ( ) ( ) (0.7- L3) neoplasms ( ) ( ) ( ) ( ) Benign Values expressed as means; 95% Cl in parentheses. NS

6 824 BLOOD FLOW IN FUNCTIONAL CYSTS J Ultrasound Med 16; Alcazar JL, Ruiz-Perez ML, Errasti T: Transvaginal color Doppler sonography in adnexal masses: Which parameter performs best? Ultrasound Obstet Gynecol8:114, Fleischer AC, Cullinan JA, ]ones HW, et a!: Serial assessment of adnexal masses with transvaginal color Doppler sonography. Ultrasound Med Biol21:435, Osmers RGW, Osmers M, von Maydell 8, et a!: Preoperative evaluation of ovarian tumors in the premenopause by transvaginosonography. Am J Obstet Gyneco1175:428, Disaia PJ, Creasman WT (Eds): Clinical Gynecologic Oncology. 4th Ed. St Louis, CV Mosby, Fuller ME: Oral contraceptive therapy for differentiating ovarian cysts. Postgrad Med 50:143, Spanos WJ: Preoperative hormonal therapy for cystic adnexal masses. Am J Obstet Gynecol116:551, teinkampf MP, Hammond KR, Blackwell RE: Hormonal treatment of functional ovarian cysts; A randomized, prospective study. Fertil Steril54:775, Turan C, Zorlu CG, Ugur M, et al: Expectant management of functional ovarian cysts: An alternative to hormonal therapy. Int J Gynecol Obstet 47:257, Osmers R: Sonographic evaluation of ovarian masses and its therapeutical implications. Ultrasound Obstet Gynecol8 :217, Kurjak A, Predanic M, Kupesic-Urek 5, et al: Transvaginal color and pulsed Doppler assesment of adnexal tumor vascularity. Gynecol Oncol 50:3, Kurjak A, Kupesic 5: Normal and abnormal ovarian circulation. /11 Kurjak A (Ed): Ultrasound and the Ovary. London, Parthenon, 1994, p Tekay A, Jouppila P: Blood flow in benign ovarian tumors and normal ovaries during the follicular phase. Obstet GyrK.>col 86:55, 1995