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Simple ovarian cysts in postmenopausal women: scope of conservative management
European Journal of Obstetrics & Gynecology and Reproductive Biology 162 (2012) 75–78
Contents lists available at SciVerse ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Simple ovarian cysts in postmenopausal women: scope of conservative management Madhutandra Sarkar a,b,*, Mark G. Wolf b a b
Department of Community Medicine, Chettinad Hospital and Research Institute, Chennai, TN, India Department of Obstetrics and Gynecology, St. Francis Hospital and Medical Center, Hartford, CT, USA
A R T I C L E I N F O
A B S T R A C T
Article history: Received 27 April 2011 Received in revised form 10 November 2011 Accepted 12 December 2011
Objective: This study was done to evaluate/investigate the natural history of simple ovarian cysts in postmenopausal women and to determine the risk for malignant transformation of these cysts. Study design: Ultrasound reports of all the postmenopausal women who attended St. Francis Hospital and Medical Center, Hartford, USA from January 1997 to April 2010 with an ultrasound diagnosis of simple cysts of ovary were reviewed retrospectively. A total of 619 patients with 743 simple ovarian cysts were evaluated. It was found that 305 out of 619 patients (49.27%) were lost in follow-up. Therefore, 314 patients (50.73%) with 378 cysts could be followed further by ultrasound study. Results: One hundred and seventy-five (46.30%) of the 378 cysts that could be followed further had spontaneous resolution and 166 cysts (43.91%) persisted unchanged over the follow-up period. Thirty cysts (7.94%) turned into complex cysts and four cysts (1.06%) significantly increased in size. One cyst significantly decreased in size, though it did not resolve. Only one patient developed papillary serous carcinoma (high grade) of the ovary. This occurred three years after her last ultrasound for simple cyst surveillance. Conclusion: Simple ovarian cysts during the menopause can be followed conservatively because their risk for malignant transformation is low. The majority of these cysts either resolve spontaneously or persist unaltered on follow-up. ß 2012 Elsevier Ireland Ltd. All rights reserved.
Keywords: Ovarian cyst Postmenopausal Management Conservative
1. Introduction Simple cysts of the ovary are quite common among the postmenopausal women, although the prevalence is lower than in premenopausal women. Prevalence of simple ovarian cysts in postmenopausal women may range from 3% to 15%. Ovarian cysts may be discovered either as a result of screening, or investigations performed for a suspected pelvic mass, or incidentally following investigations carried out for other reasons. Increasing use of ultrasound has resulted in increasing detection of these cysts. Transvaginal ultrasound is useful to look for ovarian abnormalities. Ovarian cysts should normally be assessed using transvaginal ultrasound, as this appears to provide more detail and hence offers greater sensitivity than the transabdominal method [1]. Larger cysts may also need to be assessed transabdominally. Color-flow Doppler sonography for evaluation of pulsatility and resistance in vessels that supply potential tumors with blood may be of benefit in assessing ovarian
* Corresponding author at: 4 Kavita, DAE Township, Kalpakkam, TN 603 102, India. Tel.: +91 0979 167 3025. E-mail address: [email protected] (M. Sarkar). 0301-2115/$ – see front matter ß 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2011.12.034
cysts [2], though it does not yet have a clearly established role in assessing ovarian cysts in postmenopausal women. It is known from various studies that a significant proportion of these cysts either resolve spontaneously or remain stable on follow-up. However, these cysts may become malignant. Certain ultrasound features of cysts, such as septation, papillary projections, and abnormal Doppler flow, are suspicious of malignancy and usually managed by surgery. Ovarian cancer is the sixth most common cancer in women overall and the second most common gynecological cancer worldwide [3,4]. It is the leading cause of death from gynecological cancer. A woman’s lifetime risk for ovarian cancer is between 1% and 2%. Ovarian cancer can affect women of any age, though it most often occurs in women over 60. The appropriate management for postmenopausal simple cysts of the ovary is not very obvious. Simple cysts are usually followed conservatively, but concern about progression to malignancy may lead to surgical exploration, which in most cases would likely be for benign conditions. Measurement of tumor markers, specifically CA-125, can help in decision-making, although these markers may not necessarily be specific for ovarian cancer and lack sensitivity in early stage disease. So, there is a need for clear guidelines in this area.
76
M. Sarkar, M.G. Wolf / European Journal of Obstetrics & Gynecology and Reproductive Biology 162 (2012) 75–78
To decide on the appropriate management of a postmenopausal ovarian cyst, its natural history and the risk of malignancy should be understood. With the above background, the present study was undertaken with the following objectives: (1) To evaluate/investigate the natural history of simple cysts of ovary in postmenopausal women. (2) To determine the risk for malignant transformation of these cysts followed conservatively by ultrasound.
This study mainly presents our experience on this problem over a period of 13 years in our department. 2. Materials and methods This study was undertaken in the Gynecological Ultrasound section of the Department of Obstetrics and Gynecology, St. Francis Hospital and Medical Center, Hartford, Connecticut, USA. This section is accredited by the American Institute for Ultrasound in Medicine in obstetrical and gynecological sonography. The study was approved by the Institutional Review Board. The postmenopausal state was defined as cessation of menstruation of 12 consecutive months or more before the first ultrasound study. Postmenopausal patients with a diagnosis of simple cysts of ovary by ultrasound were considered eligible for the study. Ultrasound reports of all those women who attended the Gynecological Ultrasound section from January 1997 to April 2010 with an ultrasound diagnosis of simple cysts of ovary were retrospectively reviewed. Thus, 619 postmenopausal women were identified who attended this section at least once for ultrasound study during that time period. Simple cyst of ovary was defined as an echo-free cyst with a smooth lining and no septae or solid areas or papillary projections within the cyst cavity. All sonographic examinations were performed on Philips HDI 5000 ultrasound machines with an 8–4 MHz vaginal probe, by an experienced ultrasonographer and a dedicated physician from the Department of Obstetrics and Gynecology. Transvaginal ultrasound was performed to measure the volume of each cyst in three dimensions and also to document the ovarian morphology. All women were scanned with an empty bladder and lying in a dorsal lithotomy position. St. Francis Hospital’s electronic medical record was utilized to review the documentation of all the ultrasound examinations carried out in the Gynecological Ultrasound section. From there, the cases with simple cysts of the ovary by ultrasound were identified and the patients with menopause of 12 consecutive months or more before the first ultrasound study were included in the present study. Patients who were premenopausal or whose records contained inadequate documentation were excluded. The pathology reports of the patients who underwent surgery were also reviewed. No attempt was made to review the documentation of indications for doing ultrasound, family history of cancer, hormone use, presenting symptoms and CA-125 level measurement. In this institution, postmenopausal simple cysts of the ovary are usually managed by transabdominal and transvaginal ultrasound three times in the first year of diagnosis and then every year. The decision for surgical intervention is made either by a gynecologist or the patient, or if a significant change is noted over the follow-up period. On further analysis, it was found that 305 patients were lost in follow-up. Therefore, 314 out of 619 patients (50.73%) attended for follow-up study in this institution. Thus, 378 cysts could be followed further by ultrasound study. The simple cysts were then noted for progression to complex cyst, significant increase or decrease in size, spontaneous resolution or persistent presence.
Complex cyst was defined as development of septation or solid area or papillary projection or echogenic fluid within the cyst cavity. Ovarian cyst volume was calculated by the prolate ellipsoid formula, i.e. length width height 0.523 and expressed in cm3. Significant change in size was defined as increase or decrease in size of the cyst by 20% from the baseline. Descriptive statistics were used to present the results. 3. Results A total of 619 postmenopausal women with 743 simple ovarian cysts identified on ultrasound study were included in this study. On further analysis, it was found that 305 out of 619 patients (49.27%) were lost in follow-up. Therefore, 314 patients (50.73%) with 378 cysts could be followed further by ultrasound study. Because the indications for doing the ultrasound for the first time were not systematically recorded, the specific indication of ultrasound for each patient could not be quantified in this study. Table 1 shows that 83 patients had bilateral cysts. Twelve patients underwent surgery for the cysts, but malignancy developed in only one cyst. The mean age of the patients at diagnosis was 61 years with a range of 35–96 years. The mean volume of the cysts over the total follow-up period was 21.0 cm3 with a range of 0.1–1704.9 cm3. The mean initial volume of these cysts was 16.3 cm3 with a range of 0.1–860.4 cm3. The mean duration of follow-up for the patients who underwent follow-up study was 26.48 months with a range of 3 weeks–156 months and the mean number of examinations for those patients was 3 with a range of 2–13. Table 2 shows that of the 378 cysts that could be followed further, 175 (46.30%) had spontaneous resolution and 48.57% of these (85 out of 175 cysts) resolved within one year of diagnosis. In addition, 166 cysts (43.91%) persisted unaltered over the follow-up period. Thirty cysts (7.94%) transformed into complex cysts and four cysts (1.06%) significantly increased in size. One cyst significantly decreased in size, though it did not resolve. Two cysts though turned into complex cysts; on further follow-up they again turned back to simple cysts. Surgery was done for change in morphology from simple to complex cyst in 9 patients with 11 cysts (two patients had bilateral cysts) and for significant increase in size of the cysts in 3 patients. Pathological diagnoses were available for review from 12 patients with 14 ovarian cysts. Table 3 shows the pathological diagnoses of the ovaries in which surgery was performed. The most common pathological diagnosis was serous cystadenoma of ovary (9 out of 14 cysts or 64.30%). The other pathological diagnoses were mucinous cystadenoma, dermoid cyst, cystic endosalpingitis with focal papillary feature and cystadenofibroma of ovary. Only one Table 1 Demographic and clinical representation of the patients with postmenopausal simple cysts of ovary for the total follow-up period. Total number of cysts Total number of patients Number of patients lost in follow-up Number of patients underwent follow-up study Number of patients with bilateral cysts Number of patients underwent surgery Number of patients who developed malignancy Age of the patients (years) Number of examinationsa Duration of follow-up (months)a Cyst volumes (cm3) Initial cyst volumes (cm3) a
743 619 305 314 83 12 1 Mean: 61; range: 35–96 Mean: 3; range: 2–13 Mean: 26.48 Range: 3 weeks-156 months Mean: 21.0; range: 0.1–1704.9 Mean: 16.3; range: 0.1–860.4
For patients who underwent follow-up study.
M. Sarkar, M.G. Wolf / European Journal of Obstetrics & Gynecology and Reproductive Biology 162 (2012) 75–78 Table 2 Evaluation of postmenopausal simple ovarian cysts (n = 378). Cyst evaluation
Number of cysts (%)
Spontaneous resolution Persistent cyst Complex cyst Significant increase in size Significant decrease in size Simple to complex to simple cyst
175 166 30 4 1 2
Total
378 (100.00)
(46.30) (43.91) (7.94) (1.06) (0.26) (0.53)
patient had papillary serous carcinoma (high grade) of the ovary. This was in a patient who had developed a complex cyst accompanied by abdominal pain three years after her last ‘‘surveillance’’ ultrasound for a simple cyst. 4. Comment Postmenopausal simple cysts of the ovary are not an uncommon finding. The knowledge of the natural history of a postmenopausal ovarian cyst is very important to decide on the correct management. As the vast majority of these cysts are benign, they all require evaluation before deciding on surgical removal or careful follow-up. The literature on use of ultrasound to differentiate between malignant and benign ovarian conditions originated in 1989 in a report by Granberg et al. [5]. Since then, an extensive literature has been published on this subject. Several authors have developed scoring systems that combined many of the morphological elements into a scoring index intended to aid clinicians in their management decisions [6–8]. Adding other testing modalities such as Doppler flow study or measurement of CA-125 level increases specificity but does not increase sensitivity. The best strategy appears to be ultrasound with the use of a morphological index, with or without Doppler and CA-125 testing [9]. In the present study, the mean age of the patients at diagnosis was 61 years with a range of 35–96 years. In the study by Luja´n et al. [10], the average age of the postmenopausal women at the time of diagnosis was 50.76 years with a standard deviation of 5.55. Nardo et al. [11] reported that the mean age of the postmenopausal women with persistent unilocular ovarian cysts was 56.2 years with a range of 45–87 years. It has been observed in our study that the cyst volume at diagnosis and over the total follow-up period may vary in the range of 0.1–860.4 cm3 and 0.1–1704.9 cm3, respectively. This indicates that the volume of the cysts at diagnosis and over the total followup period may vary over a large range with the cysts still being benign. This leaves scope for careful diagnosis and follow-up. It has been observed in the present study that 90.21% of the cysts (341 out of 378 cysts) had either spontaneous resolution or unaltered persistence over the follow-up period. Very few cysts (7.94%) turned into complex forms and even fewer (1.06%) significantly increased in size. However, no specific characteristics could be found that would predict the progression of a simple cyst. Table 3 Pathological findings at surgery (n = 14). Pathological findings Serous cystadenoma Mucinous cystadenoma Cystadenofibroma Dermoid cyst Cystic endosalpingitis with focal papillary feature Papillary serous carcinoma Total
Number of cysts (%) 9 1 1 1 1 1
(64.30) (7.14) (7.14) (7.14) (7.14) (7.14)
14 (100.00)
77
Very similar observations were found by Greenlee et al. [12], who reported either persistence or disappearance of the cysts in 86% of the cases and progression of the cysts to a more complex appearance in 6% of the cases during follow-up. Similarly, Modesitt et al. [13] in their study observed that a majority of cysts (76.2%) either had spontaneous resolution or persisted unaltered. A septum or solid area developed in 21.7% of cysts. Total cyst resolution occurred within one year in 70% of cases regardless of cyst volume [13]. Similar to the present study, Conway et al. [14] showed that 82.76% of simple cysts either resolved spontaneously or persisted unaltered, although 17.24% were lost in the follow-up study. No malignant ovarian condition was identified among 26.09% women with persistent simple ovarian cysts who underwent surgery [14]. In the study by Luja´n et al. [10], the cysts disappeared spontaneously in 27.71% of the cases in the follow up of 3–36 months (mean of 14.1), in contrast to 46.30% in our study. Similar to the present study, Aubert et al. [15] in their study on simple adnexal cysts in postmenopausal women observed that the cysts either remained unchanged or disappeared in 88.8% cases. However, cysts decreased in size in 11.1% cases with no case of cyst enlargement. Similar to the findings of the present study, Levine et al. [16] in their study observed that 81% of the cysts either resolved or remained the same and 3% increased in size. The resolution rate was high in the study by Levine et al. [16] and more than half of these cysts were 1 cm in size or less. Only one malignant lesion was noted. The present study along with the similar studies conducted previously point to the fact that a good percentage of the cysts resolve spontaneously or remain unchanged. Although some of the cysts grow in volume, they remain benign. This observation makes the management decision simpler and strongly suggests close follow-up before deciding on surgery. In this study, surgery was done for change in morphology from simple to complex cyst in 9 patients with 11 cysts (two patients had bilateral cysts) and for significant increase in size of the cysts in 3 patients. However, no specific rate of progression could be determined that would merit surgery. In the study by Luja´n et al. [10], surgery was performed in 16.46% cases (n = 13), for increase in size of the cysts (11.64%) and for changes in morphology from simple to complex form (4.82%). In the study by Modesitt et al. [13], 79 of 133 patients who underwent surgery had that because of persistence or progression of ovarian cysts. The most common surgical pathology as identified in the present study was benign serous cystadenoma of ovary (64.30%). Malignancy developed in only one case. According to Modesitt et al. [13], the most common pathological diagnosis was serous cystadenoma (52%) with no case of ovarian carcinoma. The study by Conway et al. [14] showed that over 66% of the cysts were benign serous cystadenomas with no case of ovarian cancer. Luja´n et al. [10] did not find any case of carcinoma. It is reported in the previous studies and also observed in the present study that surgery is often done due to increase in cyst volume or transformation into complex cyst, though the pathology remains benign in almost all the cases. The American Congress of Obstetricians and Gynecologists (ACOG) recommends that simple cysts found incidentally during the menopause can be followed conservatively because their risk for malignant transformation is low [17]. The authors acknowledge the limitations of this study and implications for future improvement. The sample size was small and almost 50% of the patients were lost in follow-up. There should have been a quality improvement process to develop a tracking system for patients advised to return for follow-up ultrasound study. In conclusion, this study and the available literature show that simple ovarian cysts in the menopause rarely progress to cancer and therefore may be followed up conservatively. However, the
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decision should depend upon the views and symptoms of the woman and on the gynecologist’s clinical assessment. Each case should be assessed individually. The patient’s detailed history, especially reproductive and family history, genetic predisposition and the presence of any symptom should also be taken into consideration. The best diagnostic modality for evaluation of a postmenopausal simple ovarian cyst remains to be transvaginal ultrasound. Women at low risk of malignancy with cysts having characteristics that support a benign diagnosis may be followed conservatively by repeat ultrasound study with or without serum CA-125 measurement at 3- to 6-month intervals. The duration and frequency for following a postmenopausal simple cyst remains the clinician’s judgment. Patients at high risk of having ovarian cancer on the basis of risk factors or increase in size or progression to complex cyst merit further evaluation. They can be managed by surgery, and less invasive approaches should be used when possible. Other indications for surgical removal during follow-up may be abnormal Doppler flow, serum CA-125 elevation, patient’s desire for removal of the cyst and noncompliance with follow-up by ultrasound. It should be an important goal to avoid unnecessary surgery or invasive and costly testing in the vast majority of patients in whom simple cysts are benign, as the benefits of conservative management greatly outweigh the risk of malignant transformation of one of these cysts. Consequently, this attitude will also prevent undue hospitalization and socio-economic burden. References [1] Leibman AJ, Kruse B, McSweeney MB. Transvaginal sonography: comparison with transabdominal sonography in the diagnosis of pelvic masses. Am J Roentgenol 1988;151:89–92. [2] Bourne T, Campbell S, Steer C, Whitehead MI, Collins WP. Transvaginal colour flow imaging: a possible new screening technique for ovarian cancer. BMJ 1989;299:1367–70.
[3] Parkin D, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74–108. [4] Sankaranarayanan R, Ferlay J. Worldwide burden of gynaecological cancer: the size of the problem. Best Pract Res Clin Obstet Gynaecol 2006;20:207–25. [5] Granberg S, Wikland M, Jansson I. Macroscopic characterization of ovarian tumors and the relation to the histological diagnosis: criteria to be used for ultrasound evaluation. Gynecol Oncol 1989;35:139–44. [6] DePriest PD, Shenson D, Fried A, et al. A morphology index based on sonographic findings in ovarian cancer. Gynecol Oncol 1993;51:7–11. [7] Sassone AM, Timor-Tritsch IE, Artner A, Westhoff C, Warren WB. Transvaginal sonographic characterization of ovarian disease: evaluation of a new scoring system to predict ovarian malignancy. Obstet Gynecol 1991;78:70–6. [8] Ueland FR, DePriest PD, Pavlik EJ, Kryscio RJ, van Nagell Jr JR. Preoperative differentiation of malignant from benign ovarian tumors: the efficacy of morphology indexing and Doppler flow sonography. Gynecol Oncol 2003;91:46–50. [9] Myers ER, Bastian LA, Havrilesky LJ, et al. Management of adnexal mass. Evidence report/technology assessment, No. 130. AHRQ publication No. 06E004. Rockville, MD: Agency for Healthcare Research and Quality; 2006, February. Available at: http://www.ahrq.gov/downloads/pub/evidence/pdf/ adnexal/adnexal.pdf Retrieved November 13, 2010. [10] Luja´n IJE, Herna´ndez MI, Figueroa PG, Ayala AR. Prevalence of postmenopausal simple ovarian cyst diagnosed by ultrasound. Ginecol Obstet Mex 2006;74: 532–6. [11] Nardo LG, Kroon ND, Reginald PW. Persistent unilocular ovarian cysts in a general population of postmenopausal women: is there a place for expectant management? Obstet Gynecol 2003;102:589–93. [12] Greenlee RT, Kessel B, Williams CR, et al. Prevalence, incidence, and natural history of simple ovarian cysts among women > 55 years old in a large cancer screening trial. Am J Obstet Gynecol 2010;202:373.e1–e9. [13] Modesitt SC, Pavlik EJ, Ueland FR, DePriest PD, Kryscio RJ, van Nagell Jr JR. Risk of malignancy in unilocular ovarian cystic tumors less than 10 centimeters in diameter. Obstet Gynecol 2003;102:594–9. [14] Conway C, Zalud I, Dilena M, et al. Simple cyst in the postmenopausal patient: detection and management. J Ultrasound Med 1998;17:369–72. [15] Aubert JM, Rombaut C, Argacha P, Romero F, Leira J, Gomez-Bolea F. Simple adnexal cysts in postmenopausal women: conservative management. Maturitas 1998;30:51–4. [16] Levine D, Gosink B, Wolf S. Simple adnexal cysts: the natural history in postmenopausal women. Radiology 1992;184:653–9. [17] The American College of Obstetricians and Gynecologists. ACOG Practice Bulletin. Management of adnexal masses. Obstet Gynecol 2007;110: 201–14.
Contents lists available at SciVerse ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Simple ovarian cysts in postmenopausal women: scope of conservative management Madhutandra Sarkar a,b,*, Mark G. Wolf b a b
Department of Community Medicine, Chettinad Hospital and Research Institute, Chennai, TN, India Department of Obstetrics and Gynecology, St. Francis Hospital and Medical Center, Hartford, CT, USA
A R T I C L E I N F O
A B S T R A C T
Article history: Received 27 April 2011 Received in revised form 10 November 2011 Accepted 12 December 2011
Objective: This study was done to evaluate/investigate the natural history of simple ovarian cysts in postmenopausal women and to determine the risk for malignant transformation of these cysts. Study design: Ultrasound reports of all the postmenopausal women who attended St. Francis Hospital and Medical Center, Hartford, USA from January 1997 to April 2010 with an ultrasound diagnosis of simple cysts of ovary were reviewed retrospectively. A total of 619 patients with 743 simple ovarian cysts were evaluated. It was found that 305 out of 619 patients (49.27%) were lost in follow-up. Therefore, 314 patients (50.73%) with 378 cysts could be followed further by ultrasound study. Results: One hundred and seventy-five (46.30%) of the 378 cysts that could be followed further had spontaneous resolution and 166 cysts (43.91%) persisted unchanged over the follow-up period. Thirty cysts (7.94%) turned into complex cysts and four cysts (1.06%) significantly increased in size. One cyst significantly decreased in size, though it did not resolve. Only one patient developed papillary serous carcinoma (high grade) of the ovary. This occurred three years after her last ultrasound for simple cyst surveillance. Conclusion: Simple ovarian cysts during the menopause can be followed conservatively because their risk for malignant transformation is low. The majority of these cysts either resolve spontaneously or persist unaltered on follow-up. ß 2012 Elsevier Ireland Ltd. All rights reserved.
Keywords: Ovarian cyst Postmenopausal Management Conservative
1. Introduction Simple cysts of the ovary are quite common among the postmenopausal women, although the prevalence is lower than in premenopausal women. Prevalence of simple ovarian cysts in postmenopausal women may range from 3% to 15%. Ovarian cysts may be discovered either as a result of screening, or investigations performed for a suspected pelvic mass, or incidentally following investigations carried out for other reasons. Increasing use of ultrasound has resulted in increasing detection of these cysts. Transvaginal ultrasound is useful to look for ovarian abnormalities. Ovarian cysts should normally be assessed using transvaginal ultrasound, as this appears to provide more detail and hence offers greater sensitivity than the transabdominal method [1]. Larger cysts may also need to be assessed transabdominally. Color-flow Doppler sonography for evaluation of pulsatility and resistance in vessels that supply potential tumors with blood may be of benefit in assessing ovarian
* Corresponding author at: 4 Kavita, DAE Township, Kalpakkam, TN 603 102, India. Tel.: +91 0979 167 3025. E-mail address: [email protected] (M. Sarkar). 0301-2115/$ – see front matter ß 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2011.12.034
cysts [2], though it does not yet have a clearly established role in assessing ovarian cysts in postmenopausal women. It is known from various studies that a significant proportion of these cysts either resolve spontaneously or remain stable on follow-up. However, these cysts may become malignant. Certain ultrasound features of cysts, such as septation, papillary projections, and abnormal Doppler flow, are suspicious of malignancy and usually managed by surgery. Ovarian cancer is the sixth most common cancer in women overall and the second most common gynecological cancer worldwide [3,4]. It is the leading cause of death from gynecological cancer. A woman’s lifetime risk for ovarian cancer is between 1% and 2%. Ovarian cancer can affect women of any age, though it most often occurs in women over 60. The appropriate management for postmenopausal simple cysts of the ovary is not very obvious. Simple cysts are usually followed conservatively, but concern about progression to malignancy may lead to surgical exploration, which in most cases would likely be for benign conditions. Measurement of tumor markers, specifically CA-125, can help in decision-making, although these markers may not necessarily be specific for ovarian cancer and lack sensitivity in early stage disease. So, there is a need for clear guidelines in this area.
76
M. Sarkar, M.G. Wolf / European Journal of Obstetrics & Gynecology and Reproductive Biology 162 (2012) 75–78
To decide on the appropriate management of a postmenopausal ovarian cyst, its natural history and the risk of malignancy should be understood. With the above background, the present study was undertaken with the following objectives: (1) To evaluate/investigate the natural history of simple cysts of ovary in postmenopausal women. (2) To determine the risk for malignant transformation of these cysts followed conservatively by ultrasound.
This study mainly presents our experience on this problem over a period of 13 years in our department. 2. Materials and methods This study was undertaken in the Gynecological Ultrasound section of the Department of Obstetrics and Gynecology, St. Francis Hospital and Medical Center, Hartford, Connecticut, USA. This section is accredited by the American Institute for Ultrasound in Medicine in obstetrical and gynecological sonography. The study was approved by the Institutional Review Board. The postmenopausal state was defined as cessation of menstruation of 12 consecutive months or more before the first ultrasound study. Postmenopausal patients with a diagnosis of simple cysts of ovary by ultrasound were considered eligible for the study. Ultrasound reports of all those women who attended the Gynecological Ultrasound section from January 1997 to April 2010 with an ultrasound diagnosis of simple cysts of ovary were retrospectively reviewed. Thus, 619 postmenopausal women were identified who attended this section at least once for ultrasound study during that time period. Simple cyst of ovary was defined as an echo-free cyst with a smooth lining and no septae or solid areas or papillary projections within the cyst cavity. All sonographic examinations were performed on Philips HDI 5000 ultrasound machines with an 8–4 MHz vaginal probe, by an experienced ultrasonographer and a dedicated physician from the Department of Obstetrics and Gynecology. Transvaginal ultrasound was performed to measure the volume of each cyst in three dimensions and also to document the ovarian morphology. All women were scanned with an empty bladder and lying in a dorsal lithotomy position. St. Francis Hospital’s electronic medical record was utilized to review the documentation of all the ultrasound examinations carried out in the Gynecological Ultrasound section. From there, the cases with simple cysts of the ovary by ultrasound were identified and the patients with menopause of 12 consecutive months or more before the first ultrasound study were included in the present study. Patients who were premenopausal or whose records contained inadequate documentation were excluded. The pathology reports of the patients who underwent surgery were also reviewed. No attempt was made to review the documentation of indications for doing ultrasound, family history of cancer, hormone use, presenting symptoms and CA-125 level measurement. In this institution, postmenopausal simple cysts of the ovary are usually managed by transabdominal and transvaginal ultrasound three times in the first year of diagnosis and then every year. The decision for surgical intervention is made either by a gynecologist or the patient, or if a significant change is noted over the follow-up period. On further analysis, it was found that 305 patients were lost in follow-up. Therefore, 314 out of 619 patients (50.73%) attended for follow-up study in this institution. Thus, 378 cysts could be followed further by ultrasound study. The simple cysts were then noted for progression to complex cyst, significant increase or decrease in size, spontaneous resolution or persistent presence.
Complex cyst was defined as development of septation or solid area or papillary projection or echogenic fluid within the cyst cavity. Ovarian cyst volume was calculated by the prolate ellipsoid formula, i.e. length width height 0.523 and expressed in cm3. Significant change in size was defined as increase or decrease in size of the cyst by 20% from the baseline. Descriptive statistics were used to present the results. 3. Results A total of 619 postmenopausal women with 743 simple ovarian cysts identified on ultrasound study were included in this study. On further analysis, it was found that 305 out of 619 patients (49.27%) were lost in follow-up. Therefore, 314 patients (50.73%) with 378 cysts could be followed further by ultrasound study. Because the indications for doing the ultrasound for the first time were not systematically recorded, the specific indication of ultrasound for each patient could not be quantified in this study. Table 1 shows that 83 patients had bilateral cysts. Twelve patients underwent surgery for the cysts, but malignancy developed in only one cyst. The mean age of the patients at diagnosis was 61 years with a range of 35–96 years. The mean volume of the cysts over the total follow-up period was 21.0 cm3 with a range of 0.1–1704.9 cm3. The mean initial volume of these cysts was 16.3 cm3 with a range of 0.1–860.4 cm3. The mean duration of follow-up for the patients who underwent follow-up study was 26.48 months with a range of 3 weeks–156 months and the mean number of examinations for those patients was 3 with a range of 2–13. Table 2 shows that of the 378 cysts that could be followed further, 175 (46.30%) had spontaneous resolution and 48.57% of these (85 out of 175 cysts) resolved within one year of diagnosis. In addition, 166 cysts (43.91%) persisted unaltered over the follow-up period. Thirty cysts (7.94%) transformed into complex cysts and four cysts (1.06%) significantly increased in size. One cyst significantly decreased in size, though it did not resolve. Two cysts though turned into complex cysts; on further follow-up they again turned back to simple cysts. Surgery was done for change in morphology from simple to complex cyst in 9 patients with 11 cysts (two patients had bilateral cysts) and for significant increase in size of the cysts in 3 patients. Pathological diagnoses were available for review from 12 patients with 14 ovarian cysts. Table 3 shows the pathological diagnoses of the ovaries in which surgery was performed. The most common pathological diagnosis was serous cystadenoma of ovary (9 out of 14 cysts or 64.30%). The other pathological diagnoses were mucinous cystadenoma, dermoid cyst, cystic endosalpingitis with focal papillary feature and cystadenofibroma of ovary. Only one Table 1 Demographic and clinical representation of the patients with postmenopausal simple cysts of ovary for the total follow-up period. Total number of cysts Total number of patients Number of patients lost in follow-up Number of patients underwent follow-up study Number of patients with bilateral cysts Number of patients underwent surgery Number of patients who developed malignancy Age of the patients (years) Number of examinationsa Duration of follow-up (months)a Cyst volumes (cm3) Initial cyst volumes (cm3) a
743 619 305 314 83 12 1 Mean: 61; range: 35–96 Mean: 3; range: 2–13 Mean: 26.48 Range: 3 weeks-156 months Mean: 21.0; range: 0.1–1704.9 Mean: 16.3; range: 0.1–860.4
For patients who underwent follow-up study.
M. Sarkar, M.G. Wolf / European Journal of Obstetrics & Gynecology and Reproductive Biology 162 (2012) 75–78 Table 2 Evaluation of postmenopausal simple ovarian cysts (n = 378). Cyst evaluation
Number of cysts (%)
Spontaneous resolution Persistent cyst Complex cyst Significant increase in size Significant decrease in size Simple to complex to simple cyst
175 166 30 4 1 2
Total
378 (100.00)
(46.30) (43.91) (7.94) (1.06) (0.26) (0.53)
patient had papillary serous carcinoma (high grade) of the ovary. This was in a patient who had developed a complex cyst accompanied by abdominal pain three years after her last ‘‘surveillance’’ ultrasound for a simple cyst. 4. Comment Postmenopausal simple cysts of the ovary are not an uncommon finding. The knowledge of the natural history of a postmenopausal ovarian cyst is very important to decide on the correct management. As the vast majority of these cysts are benign, they all require evaluation before deciding on surgical removal or careful follow-up. The literature on use of ultrasound to differentiate between malignant and benign ovarian conditions originated in 1989 in a report by Granberg et al. [5]. Since then, an extensive literature has been published on this subject. Several authors have developed scoring systems that combined many of the morphological elements into a scoring index intended to aid clinicians in their management decisions [6–8]. Adding other testing modalities such as Doppler flow study or measurement of CA-125 level increases specificity but does not increase sensitivity. The best strategy appears to be ultrasound with the use of a morphological index, with or without Doppler and CA-125 testing [9]. In the present study, the mean age of the patients at diagnosis was 61 years with a range of 35–96 years. In the study by Luja´n et al. [10], the average age of the postmenopausal women at the time of diagnosis was 50.76 years with a standard deviation of 5.55. Nardo et al. [11] reported that the mean age of the postmenopausal women with persistent unilocular ovarian cysts was 56.2 years with a range of 45–87 years. It has been observed in our study that the cyst volume at diagnosis and over the total follow-up period may vary in the range of 0.1–860.4 cm3 and 0.1–1704.9 cm3, respectively. This indicates that the volume of the cysts at diagnosis and over the total followup period may vary over a large range with the cysts still being benign. This leaves scope for careful diagnosis and follow-up. It has been observed in the present study that 90.21% of the cysts (341 out of 378 cysts) had either spontaneous resolution or unaltered persistence over the follow-up period. Very few cysts (7.94%) turned into complex forms and even fewer (1.06%) significantly increased in size. However, no specific characteristics could be found that would predict the progression of a simple cyst. Table 3 Pathological findings at surgery (n = 14). Pathological findings Serous cystadenoma Mucinous cystadenoma Cystadenofibroma Dermoid cyst Cystic endosalpingitis with focal papillary feature Papillary serous carcinoma Total
Number of cysts (%) 9 1 1 1 1 1
(64.30) (7.14) (7.14) (7.14) (7.14) (7.14)
14 (100.00)
77
Very similar observations were found by Greenlee et al. [12], who reported either persistence or disappearance of the cysts in 86% of the cases and progression of the cysts to a more complex appearance in 6% of the cases during follow-up. Similarly, Modesitt et al. [13] in their study observed that a majority of cysts (76.2%) either had spontaneous resolution or persisted unaltered. A septum or solid area developed in 21.7% of cysts. Total cyst resolution occurred within one year in 70% of cases regardless of cyst volume [13]. Similar to the present study, Conway et al. [14] showed that 82.76% of simple cysts either resolved spontaneously or persisted unaltered, although 17.24% were lost in the follow-up study. No malignant ovarian condition was identified among 26.09% women with persistent simple ovarian cysts who underwent surgery [14]. In the study by Luja´n et al. [10], the cysts disappeared spontaneously in 27.71% of the cases in the follow up of 3–36 months (mean of 14.1), in contrast to 46.30% in our study. Similar to the present study, Aubert et al. [15] in their study on simple adnexal cysts in postmenopausal women observed that the cysts either remained unchanged or disappeared in 88.8% cases. However, cysts decreased in size in 11.1% cases with no case of cyst enlargement. Similar to the findings of the present study, Levine et al. [16] in their study observed that 81% of the cysts either resolved or remained the same and 3% increased in size. The resolution rate was high in the study by Levine et al. [16] and more than half of these cysts were 1 cm in size or less. Only one malignant lesion was noted. The present study along with the similar studies conducted previously point to the fact that a good percentage of the cysts resolve spontaneously or remain unchanged. Although some of the cysts grow in volume, they remain benign. This observation makes the management decision simpler and strongly suggests close follow-up before deciding on surgery. In this study, surgery was done for change in morphology from simple to complex cyst in 9 patients with 11 cysts (two patients had bilateral cysts) and for significant increase in size of the cysts in 3 patients. However, no specific rate of progression could be determined that would merit surgery. In the study by Luja´n et al. [10], surgery was performed in 16.46% cases (n = 13), for increase in size of the cysts (11.64%) and for changes in morphology from simple to complex form (4.82%). In the study by Modesitt et al. [13], 79 of 133 patients who underwent surgery had that because of persistence or progression of ovarian cysts. The most common surgical pathology as identified in the present study was benign serous cystadenoma of ovary (64.30%). Malignancy developed in only one case. According to Modesitt et al. [13], the most common pathological diagnosis was serous cystadenoma (52%) with no case of ovarian carcinoma. The study by Conway et al. [14] showed that over 66% of the cysts were benign serous cystadenomas with no case of ovarian cancer. Luja´n et al. [10] did not find any case of carcinoma. It is reported in the previous studies and also observed in the present study that surgery is often done due to increase in cyst volume or transformation into complex cyst, though the pathology remains benign in almost all the cases. The American Congress of Obstetricians and Gynecologists (ACOG) recommends that simple cysts found incidentally during the menopause can be followed conservatively because their risk for malignant transformation is low [17]. The authors acknowledge the limitations of this study and implications for future improvement. The sample size was small and almost 50% of the patients were lost in follow-up. There should have been a quality improvement process to develop a tracking system for patients advised to return for follow-up ultrasound study. In conclusion, this study and the available literature show that simple ovarian cysts in the menopause rarely progress to cancer and therefore may be followed up conservatively. However, the
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decision should depend upon the views and symptoms of the woman and on the gynecologist’s clinical assessment. Each case should be assessed individually. The patient’s detailed history, especially reproductive and family history, genetic predisposition and the presence of any symptom should also be taken into consideration. The best diagnostic modality for evaluation of a postmenopausal simple ovarian cyst remains to be transvaginal ultrasound. Women at low risk of malignancy with cysts having characteristics that support a benign diagnosis may be followed conservatively by repeat ultrasound study with or without serum CA-125 measurement at 3- to 6-month intervals. The duration and frequency for following a postmenopausal simple cyst remains the clinician’s judgment. Patients at high risk of having ovarian cancer on the basis of risk factors or increase in size or progression to complex cyst merit further evaluation. They can be managed by surgery, and less invasive approaches should be used when possible. Other indications for surgical removal during follow-up may be abnormal Doppler flow, serum CA-125 elevation, patient’s desire for removal of the cyst and noncompliance with follow-up by ultrasound. It should be an important goal to avoid unnecessary surgery or invasive and costly testing in the vast majority of patients in whom simple cysts are benign, as the benefits of conservative management greatly outweigh the risk of malignant transformation of one of these cysts. Consequently, this attitude will also prevent undue hospitalization and socio-economic burden. References [1] Leibman AJ, Kruse B, McSweeney MB. Transvaginal sonography: comparison with transabdominal sonography in the diagnosis of pelvic masses. Am J Roentgenol 1988;151:89–92. [2] Bourne T, Campbell S, Steer C, Whitehead MI, Collins WP. Transvaginal colour flow imaging: a possible new screening technique for ovarian cancer. BMJ 1989;299:1367–70.
[3] Parkin D, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74–108. [4] Sankaranarayanan R, Ferlay J. Worldwide burden of gynaecological cancer: the size of the problem. Best Pract Res Clin Obstet Gynaecol 2006;20:207–25. [5] Granberg S, Wikland M, Jansson I. Macroscopic characterization of ovarian tumors and the relation to the histological diagnosis: criteria to be used for ultrasound evaluation. Gynecol Oncol 1989;35:139–44. [6] DePriest PD, Shenson D, Fried A, et al. A morphology index based on sonographic findings in ovarian cancer. Gynecol Oncol 1993;51:7–11. [7] Sassone AM, Timor-Tritsch IE, Artner A, Westhoff C, Warren WB. Transvaginal sonographic characterization of ovarian disease: evaluation of a new scoring system to predict ovarian malignancy. Obstet Gynecol 1991;78:70–6. [8] Ueland FR, DePriest PD, Pavlik EJ, Kryscio RJ, van Nagell Jr JR. Preoperative differentiation of malignant from benign ovarian tumors: the efficacy of morphology indexing and Doppler flow sonography. Gynecol Oncol 2003;91:46–50. [9] Myers ER, Bastian LA, Havrilesky LJ, et al. Management of adnexal mass. Evidence report/technology assessment, No. 130. AHRQ publication No. 06E004. Rockville, MD: Agency for Healthcare Research and Quality; 2006, February. Available at: http://www.ahrq.gov/downloads/pub/evidence/pdf/ adnexal/adnexal.pdf Retrieved November 13, 2010. [10] Luja´n IJE, Herna´ndez MI, Figueroa PG, Ayala AR. Prevalence of postmenopausal simple ovarian cyst diagnosed by ultrasound. Ginecol Obstet Mex 2006;74: 532–6. [11] Nardo LG, Kroon ND, Reginald PW. Persistent unilocular ovarian cysts in a general population of postmenopausal women: is there a place for expectant management? Obstet Gynecol 2003;102:589–93. [12] Greenlee RT, Kessel B, Williams CR, et al. Prevalence, incidence, and natural history of simple ovarian cysts among women > 55 years old in a large cancer screening trial. Am J Obstet Gynecol 2010;202:373.e1–e9. [13] Modesitt SC, Pavlik EJ, Ueland FR, DePriest PD, Kryscio RJ, van Nagell Jr JR. Risk of malignancy in unilocular ovarian cystic tumors less than 10 centimeters in diameter. Obstet Gynecol 2003;102:594–9. [14] Conway C, Zalud I, Dilena M, et al. Simple cyst in the postmenopausal patient: detection and management. J Ultrasound Med 1998;17:369–72. [15] Aubert JM, Rombaut C, Argacha P, Romero F, Leira J, Gomez-Bolea F. Simple adnexal cysts in postmenopausal women: conservative management. Maturitas 1998;30:51–4. [16] Levine D, Gosink B, Wolf S. Simple adnexal cysts: the natural history in postmenopausal women. Radiology 1992;184:653–9. [17] The American College of Obstetricians and Gynecologists. ACOG Practice Bulletin. Management of adnexal masses. Obstet Gynecol 2007;110: 201–14.