- Email: [email protected]
Adnexal masses and pregnancy: a 12-year experience
Adnexal masses and pregnancy: A 12-year experience Gordon B. Sherard III, MD,a Charles A. Hodson, PhD,a H. James Williams, MD,b Diane A. Semer, MD,a Hamid A. Hadi, MD,a and David L. Tait, MDa Greenville, NC OBJECTIVE: Our purpose was to describe pregnancy-associated adnexal masses in eastern North Carolina. STUDY DESIGN: A retrospective study was performed of 60 adnexal masses resected during pregnancy at a regional referral hospital from January 1990 to March 2002. RESULTS: Adnexal masses occurred in 0.15% of pregnancies. Average gestational age at diagnosis and surgery was 12 and 20 weeks, respectively. Fifty percent of ovarian tumors were mature cystic teratomas, 20% were cystadenomas, and 13% were functional ovarian cysts. Malignancy occurred in 13%. Tumors with low malignant potential comprised 63% of malignancies. Average cyst size was 11.5 cm for malignancies and 7.6 cm for benign lesions (P value <.05). The preterm birth rate was 9%, the miscarriage rate was 4.7% after elective cases, and average Apgar scores were 7.5 and 8.7 at 1 and 5 minutes. CONCLUSION: The incidence of malignancy in pregnancy-associated adnexal masses was high. Ultrasonography detected internal excrescences in the majority of tumors with low malignant potential. Fetal outcomes were not affected. (Am J Obstet Gynecol 2003;189:358-63.)
Key words: Adnexal masses, malignancy, pregnancy
The number of adnexal masses diagnosed concurrently with pregnancy has increased as the routine use of ultrasonography has increased. The use of ultrasonography has resulted in the detection of asymptomatic and clinically inapparent lesions.1 Historically, adnexal masses were diagnosed on physical examination. Earlier diagnosis of pregnancy as a result of very sensitive home pregnancy tests and increased access to prenatal care may contribute to increased detection of pregnancy-associated masses. As more women enter into prenatal care at earlier gestational ages, the incidence of lesions increases as more functional cysts are detected. Currently, adnexal masses have been noted to occur in up to 1% of all gestations.1 The management of adnexal masses associated with pregnancy is variable. The two most common options are operative extirpation of the mass or expectant management. Cyst size, gestational age, and sonographic appearance all need to be considered when evaluating adnexal masses and formulating a treatment plan. Previous studies have both supported and refuted complications associated with these options of therapy. The histologic
From the Departments of Obstetrics and Gynecology,a and Pathology,b East Carolina University, Brody School of Medicine, Pitt County Memorial Hospital. Presented at Sixty-Fifth Annual Meeting of the South Atlantic Association of Obstetricians and Gynecologists, Hot Springs, Va, January 25-28, 2003. Reprint requests: Gordon B. Sherard III, MD, 201 Pineville Rd, Spartanburg, SC 29307. E-mail: [email protected] Ó 2003, Mosby, Inc. All rights reserved. 0002-9378/2003 $30.00 + 0 doi:10.1067/S0002-9378(03)00731-2
358
diagnoses most commonly reported for these persistent masses are functional cysts and mature cystic teratomas. The incidence of ovarian cancer associated with persistent adnexal masses in pregnancy varies, with reports as high as 5.9%.2 The purpose of this article was to characterize the adnexal masses associated with pregnancy at a tertiary care facility and to report on the maternal and fetal outcomes. The description of the mass will include clinical presentation, ultrasound morphologic features, and histologic diagnosis. Increased data on adnexal masses in pregnancy will enhance the counseling of patients regarding management options. Material and methods This was a retrospective study of all pregnancyassociated adnexal masses that were surgically resected at Pitt County Memorial Hospital, a tertiary care facility in rural eastern North Carolina from January 1990 through March 2002. The obstetric database was reviewed for exploratory laparotomy, operative laparoscopy, adnexal mass, and pelvic mass. The pathology database was also searched for adnexal, ovarian, or pelvic mass associated with pregnancy. Data collection included maternal age, race, gravidity, parity, gestational age at diagnosis, gestational age at surgery, gestational age at delivery, ultrasonographic findings, site of lesion, pregnancy complications, neonatal complications, birth weight, Apgar scores, and histologic diagnosis of the adnexal masses. Mean diameter of the mass was calculated as the sum of three diameters divided by 3. Term deliveries were defined as occurring after 37 weeks and up to 42 weeks of
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Table I. Maternal demographics (n = 56) Average maternal age Average gravidity Average parity Nulliparous Race African-American White Other Complications of pregnancy Diabetes Hypertension Asthma Sickle cell disease/trait Thyroid dysfunction Advanced maternal age Lupus erythematosus Rh negative (nonsensitized) Twins Tobacco use Pyelonephritis
Table II. Neonatal data (n = 42) 27 y 2.4 0.9 45%
(15-41y) (1-7) (0-5) (n = 25)
59% (n = 33) 36% (n = 20) 5% (n = 3) 9% 5% 2% 4% 2% 12.5% 2% 9% 3% 2% 2%
(n (n (n (n (n (n (n (n (n (n (n
= = = = = = = = = = =
5) 3) 1) 2) 1) 7) 1) 5) 3) 1) 1)
gestation and preterm deliveries were defined as occurring before 37 weeks of gestation. The decision on whether to operate was determined by the staff physician and/or maternal fetal medicine specialist. Microsoft Excel statistical software was used to preform two-tailed t tests on the mean cyst diameter. Results There were 37,929 deliveries during the study period. Sixty-three patients with adnexal masses were identified through our database searches. Of the 63 patients, 7 were lost to follow-up and not included in our study resulting in a final study group of 56 patients. After patients with bilateral disease were included, the total number of adnexal masses was 60, giving an incidence of 0.15% (1/632 pregnancies) in our series. Mean maternal age and parity were 27 years and 1, respectively (Table I). The mean gestational age at diagnosis of the adnexal mass was 12 weeks and the mean gestational age at surgery was 20 weeks. Fourteen cases (22%) were diagnosed during the first trimester at an average gestational age of 9 weeks (6-11 weeks). After documenting no spontaneous resolution, these masses were removed at an average gestational age of 17 weeks. During the 12th to 20th gestational week, 17 more masses were discovered at an average gestational age of 16 weeks (12-20 weeks). The average gestational age at surgery was 23 weeks for these masses. Thirty-one of the 56 (55%) study patients underwent surgery on or before completion of the 20th gestational week. The remainder had operations either at cesarean section or immediately post partum. Nine patients were followed up expectantly after diagnosis with the average length of antepartum follow-up lasting 17 weeks (range 7-26 weeks). Seventeen patients had masses removed at cesarean section and 5 patients had laparotomies in the immediate postpartum period.
Gestational age at delivery Term delivery Preterm delivery Spontaneous abortion Elective abortion Route of delivery Vaginal delivery Cesarean delivery Curettage Average birth weight Average Apgar score 1 min 5 min
37.5 ± 2.5 wk 69% (n = 29) 24% (n = 10) 4.7% (n = 2) 2.3% (n = 1) 44% (n = 19) 54% (n = 23) 2% (n = 1) 2877 ± 911 g 7.5 8.7
± 0.59 ± 0.19
Fifty-four operations (96%) were by laparotomy and the two most recent surgeries were laparoscopic procedures. Ninety-eight percent (55/56) of our cases were elective cases. One emergency surgery for adnexal torsion was preformed. Vertical midline incisions were used in the majority of the laparotomy cases. The two laparoscopic cases were preformed at 15 and 17 weeks gestation for one mature cystic teratoma and one functional cyst, respectively. Traditional pressure values of 15 mm Hg were used for insufflation. Neonatal information was only available for 42 of 56 patients (75%) as a result of patients returning to the referring physicians after evaluation and management of the adnexal mass. Term delivery occurred in 69% of patients. Preterm deliveries included two sets of twins and two inductions of labor for nonreassuring fetal status. Mean 1 and 5 minute Apgar scores were 7.5 and 8.7 (Table II). Fifty percent (30/60) of the lesions were mature cystic teratomas, 13% were functional ovarian cysts, and 20% were benign cystadenomas. The incidence of cancer associated with adnexal masses in pregnancy was 13%. Low malignant potential tumors comprised 63% (5/8) of malignant neoplasms, whereas the remaining 37% (3/8) displayed stromal invasion (Table III). The mean cyst size for nonmalignant masses was 7.6 cm (range 3 cm to 15cm) and 11.5 cm for malignant masses (range 6 cm to 17 cm). Septations were found equivalently in malignant and nonmalignant processes. Internal excrescences were found in 50% of malignant tumors and not in any benign lesions (Table IV). The Federation of International Gynecology and Obstetrics (FIGO) system was used to surgically stage the ovarian cancers. Cell washings, peritoneal biopsies, lymph node sampling, and partial omentectomies were performed. At diagnosis, all the cancers were FIGO stage IA. Maternal data for patients with ovarian cancer is presented in Table V. Ascites, a frequent coexisting condition with ovarian cancer, was detected by ultrasonography in two cases in our series. One case was a luteoma (functional cyst) and the other was an immature teratoma
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Table III. Adnexal mass pathology Histologic diagnosis
%
Mature cystic teratoma (n = 30) Cystadenoma (n = 12) Functional (n = 8) Cancer (n = 8)* Fibroma (n = 1) Paratubal (n = 1)
Table V. Ovarian cancer demographics Calculated mean cyst size (cm)
50 20 13 13 2 2
6.2 ± 2.1 11 ± 3.9 7.4 ± 3 11.5 ± 3.9 3 7
(3-11) (4-13) (4-13) (6-17)
*Four papillary serous, low malignant potential; 1 mucinous, low malignant potential; 2 immature teratomas; 1 dysgerminoma.
Table IV. Ultrasound data (n = 40)
Morphology Complex Solid Cystic Discriminator Internal excrescences Echogenic focus Septated
Benign (n = 32)
Malignant (n = 8)
66% (n = 21) 13% (n = 4) 22% (n = 7)
87.5% (n = 7) 12.5 (n = 1) 0%
0% 3% (n = 1) 9% (n = 3)
50% (n = 4) 0% 13% (n = 1)
that actually had an intact ovarian capsule at time of operation. The ultrasound was misleading because of the extremely large nature (>2 L) of the cystic component of the neoplasm. Comment In our large series of adnexal masses in pregnancy, we found the distribution of histology variable from other reports. Although the incidence of cystadenomas associated with adnexal masses in pregnancy was similar in our study compared with prior studies, we had several findings that differed from what had previously been reported. The 50% incidence of mature cystic teratomas in our series was increased over the previously reported 20% to 30% incidence. Functional cysts occurred in only 13% of our cases compared with previous ranges between 22% to 54%. The most striking finding in our series, however, was the increased incidence of malignancy in persistent adnexal masses in pregnancy. The 13% incidence is over twice the previously reported incidence of 2% to 6%.3 Pregnancy outcomes in our series are consistent with previous reports. The postoperative spontaneous abortion rate after elective removal was 4.6%. One emergency surgery was preformed in a patient at 20 weeks gestational age as a result of ovarian torsion; she was delivered uneventfully at term. The overall incidence of preterm birth was 24% (10/42). When adjusted for two pairs of twins and two inductions of labor for fetal indications, the rate of preterm delivery decreases to 9%.
Average maternal age Average gravidity Average parity Nulliparous Race African American White Site Right Left Bilateral
22 y 2.3 1 57%
(15-38y) (1-5) (0-3) (n = 4)
43% (n = 3) 57% (n = 4) 57% (n = 4) 29% (n = 2) 14% (n = 1)
Multiple authors have recommended conservative management of adnexal masses #6 cm. Grimes et al4 reported 185 adnexal masses; 111 cysts were diagnosed during pregnancy and expectantly managed. Ninety-two of 98 (94%) cysts that were less than 6 cm spontaneously resolved. These authors proposed that the pedicle is able to resist torsion as long as the cyst is not greater than 6 cm. A separate study reporting on 137 masses noted that 31 of 38 (82%) cysts less than 6 cm resolved.5 All cysts 5 cm or less resolved in the largest series that described 131 pregnancy-associated adnexal masses.6 In addition to the possibility of spontaneous cyst resolution, the decision to postpone surgery until after the first trimester has been based on cases described in the Emil Novak Tumor registry. One third of all surgeries preformed in the first trimester ended in spontaneous abortion in that series.7 These data are a common guideline for timing elective operative removal of adnexal masses in pregnancy. Expectant management has been associated with adverse pregnancy outcome if the mass undergoes torsion, rupture, or hemorrhage. Hess et al2 reported 15 of 54 (28%) patients with adnexal masses found in pregnancy required emergency laparotomy (6 acute hemorrhage, 7 cyst torsion). Of these patients requiring emergency surgery, 6 of 15 (40%) had adverse pregnancy outcomes postoperatively, four spontaneous abortions and two preterm births. Of the remaining 39 patients who had elective removal of an adnexal mass, only 1 (2%) had an adverse pregnancy outcome. Interestingly, seven cases in this series involved the removal of a corpus luteum, including five that had to have emergency surgery. Two patients had postoperative spontaneous abortions for an incidence of 29% (2/7). In our study, 2 of 42 (4.7%) patients with available delivery data had an adverse pregnancy outcome after elective removal of an adnexal mass. One patient had a spontaneous abortion immediately after surgery at 16 weeks. The other patient had premature rupture of membranes at 18 weeks after amniocentesis for advanced maternal age at 15 weeks and surgery at 15.3 weeks of gestation.
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The effect of pregnancy on mature cystic teratomas has also been evaluated and one study noted increased complications. Torsion occurred in 19% and rupture in 17% of these cysts in pregnancy.8 Because of the high incidence of adverse pregnancy outcomes in association with emergency surgery previously reported, some authors recommend elective removal of all masses that persist until 16 weeks and are 6 cm or greater regardless of appearance on imaging studies, unless it is suspected to be a leiomyoma.2 Conversely, torsion occurred in only 1 of 139 conservatively managed patients in the study by Grimes et al.4 At surgery, the ovarian pedicle was untwisted and a cystectomy was performed on a 10-cm cyst. The patient had no postoperative pregnancy-related complications. There were no complications in a study that expectantly followed up 49 patients with presumed dermoids. Pregnancy did not affect the growth of mature cystic teratomas 6 cm or less in these patients.9 Twelve patients were followed up, and there was no incidence of torsion in another study.10 In the 9 patients we managed conservatively with mature cystic teratomas (average cyst size 6.3 cm), torsion did not occur. The length of follow-up for these patients ranged from 7weeks to 26 weeks. Only 1 patient in our series was diagnosed with torsion (on initial presentation for care at 20 weeks’ gestation) and taken to the operating room. Postoperatively, she had no further antenatal complications and was delivered at term. Gross and microscopic examination to exclude a malignant neoplasm is an indication for operative intervention. The reported incidence of ovarian cancer in pregnancy ranges from 1:5000 to 1:47,000 live births with 2% to 6% of persistent adnexal masses being malignant.7,10 Tumors with low malignant potential and epithelial cancers are the most common ovarian cancers found in pregnancy.11 In our series, 13% (8/60) of persistent adnexal masses were malignant. The malignancy rate in our series was 1 in 4741 pregnancies. In agreement with a previously reported study describing ovarian cancer in pregnancy, the majority of cancers in our series were tumors of low malignant potential.12 Size has been used as an indicator for surgery in nonpregnant patients. Historic recommendations have been to remove masses that were larger than 8 cm or masses between 5 and 8 cm that did not resolve after 8 weeks in menstruating women.13 In our series, the average mean cyst size was 11.5 cm for malignant lesions and 11 cm for cystadenomas (P value not significant) (Table III). However, the average mean cyst size for all benign lesions was 7.6 cm (P value <.05). Thus, using size alone as an absolute discriminator does not appear to be predictive, unless the lesion is less than 6 cm. Ultrasound evaluation of adnexal masses has been utilized in the attempt to differentiate between malignant and benign tumors. Different evaluation techniques using
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weighted scoring systems (including septations, wall structure, and echogenicity) exist. The difficulty in differentiating certain benign conditions from malignancy has yielded positive predictive values around 30%.14 In another study, the ultrasound in 15% of the cases was ‘‘frankly misleading.’’15 Included were 6% of cases interpreted as benign when a malignancy was documented by histologic study. Twenty-two percent of ultrasonographic simple cysts were noted on pathologic examination to be low malignant potential tumors in a separate study.6 In our cases, 80% (4/5) of masses that were of low malignant potential had ultrasonographic morphologic features significant for papillary excrescences detected on the internal cyst wall. Solid tumors are another frequently cited reason for surgery over concerns for malignancy. Of the six solid tumors in our series, four (66%) were benign, including a luteoma, a fibroma, and two mature cystic teratomas. There were two malignancies (33%), an immature teratoma and a dysgerminoma (Table V). Color-flow Doppler imaging has also been used as an adjunct in evaluating adnexal masses. Building on the presence of neovascularization and the associated low resistance vessels (because of the absence of muscularis development) in malignancy, descriptions of pulsatility and resistance indices have been published.16 However, no such data have been reported for adnexal masses in pregnancy. Magnetic resonance imaging (MRI) is another imaging modality that has been used to assist in the characterization of adnexal masses. In one published study, magnetic resonance imaging (MRI) was used in the differentiation between solid ovarian masses and leiomyoma.17 More information and studies on the benefits of MRI are needed before its routine use in the work-p of pregnancyassociated adnexal masses. In summation, we found a much higher than expected malignancy rate. We postulate that as a regional center, our malignancy rate is higher because lesions that are smaller or more benign appearing are managed by private practitioners and not referred. Importantly, the size of the ovarian mass diagnosed in pregnancy was not absolutely predictive of malignancy. However, all masses less than 6 cm were noted to be benign. Morphologic study, as characterized by ultrasonography, detected internal papillary excrescences in 50% of malignancies in our series. Neonatal outcome was not adversely affected in either elective cases or our only emergency surgery. Our data support that of other published studies, to manage masses conservatively, performing surgery in the second trimester. We conclude that patients with persistent adnexal masses greater than 6 cm should undergo surgical removal, be appropriately counseled as to the possibility of an underlying malignancy, and be prepared for possible ovarian cancer staging.
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REFERENCES 1. Nelson MJ, Cavalieri R, Sanders RC. Cysts in pregnancy discovered by sonography. J Clin Ultrasound 1986;14:509-12. 2. Hess LW, Peaceman A, O’Brien WF, Winkel CA, Cruikshank DP, Morrison JC. Adnexal mass occurring with intrauterine pregnancy: report of fifty-four patients requiring laparotomy for definitive management. Am J Obstet Gynecol 1988;158:1029-34. 3. Liu JR, Lilja JF, Johnston C. Adnexal masses and ovarian cancer in pregnancy. In: Trimble EL, Trimble CL, editors. Cancer obstetrics and gynecology. Philadelphia: Lippincott-Williams & Wilkins; 1999. p. 239-48. 4. Grimes WH, Bartholomew RA, Colvin ED, Fish JS, Lester WM. Ovarian cyst complicating pregnancy. Am J Obstet Gynecol 1954;68:594-603. 5. Hogston P, Lilford RJ. Ultrasound study of ovarian cysts in pregnancy: prevalence and significance. BJOG 1986;93:625-8. 6. Thornton JG, Wells M. Ovarian cysts in pregnancy: does ultrasound make traditional management inappropriate. Obstet Gynecol 1987;69:717-21. 7. Novak ER, Lambrou CD, Woodruff JD. Ovarian tumors in pregnancy: an ovarian tumor registry review. Obstet Gynecol 1975;46:401-6. 8. Peterson WF, Prevost EC, Edmunds FT, Hundley JM, Morris FK. Benign cystic teratomas of the ovary. Am J Obstet Gynecol 1955;70:368-82. 9. Caspi B, Levi R, Appelman Z, Rabinerson D, Goldman G, Hagay Z. Conservative management of ovarian cystic teratoma during pregnancy and labor. Am J Obstet Gynecol 2000;182:503-5. 10. Platelek DN, Henderson CE, Goldberg GL. The management of a persistent adnexal mass in pregnancy. Am J Obstet Gynecol 1995;173:1236-40. 11. Ovarian Tumor Panel of the Royal College of Obstetricians and Gynecologists. Ovarian epithelial tumours of borderline malignancy: pathological features and current status. BJOG 1983;90:743-50. 12. Dgani R, Shoham Z, Atar E, Zosmer A, Lancet M. Ovarian carcinoma during pregnancy: a study of 23 cases in Israel between the years 1960 and 1984. Gynecol Oncol 1989;33:326-31. 13. Droegemueller W. Benign gynecological lesions. In: Mishell DR, Stenchever MA, Droegemueller W, Herbst AL, editors. Comprehensive gynecology. 3rd ed. St. Louis: Mosby; 1997. p. 467-516. 14. Lerner JP, Timor-Tritsch IE, Federman A, Abramovich G. Transvaginal ultrasonographic characterization of ovarian masses with an improved, weighted scoring system. Am J Obstet Gynecol 1994;170:81-5. 15. Benacerraf BR, Finkler NJ, Wojciechowski C, Knapp RC. Sonographic accuracy in the diagnosis of ovarian masses. J Reprod Med 1990;35:491-5. 16. Fleischer AC, Kepple DM. Color Doppler sonography of pelvic masses. In: Fleischer AC, Manning FA, Jeanty P, Romero R, editors. Sonography in obstetrics and gynecology. 6th ed. New York: McGrawHill; 2001. p. 913-47. 17. Curtis M, Hopkins MP, Zarlingo T, Martino C, Graciansky-Lengyl M, Jenison EL. Magnetic resonance imaging to avoid laparotomy in pregnancy. Obstet Gynecol 1993;82:833-6.
Discussion DR JERRY F. MATKINS JR, Gastonia, NC. The detection of adnexal masses in pregnancy has become increasingly more common, and therefore the dilemma of how to manage these patients has become one that is faced more frequently. In the era before ultrasound, when palpation was relied on to diagnose adnexal masses, the detection rate was reported to be 1 in 591 pregnancies.1 By 1986, as ultrasound became more commonly used, the reported incidence of adnexal masses in pregnancy was 1 in 190.2 Because ultrasound has become more precise over the past 15 years, that detection rate has climbed to as high as one mass detected in every 50 pregnancies.3 Certainly all of these lesions are not clinically significant, so we cannot say with assurance that our increased technologic capabilities have resulted in better management of patients. In fact, we may have only succeeded in raising
August 2003 Am J Obstet Gynecol
anxiety levels. It is in addressing the question of whether what we can now detect is truly significant, and if so when, that studies such as Dr Sherard’s are helpful. The authors retrospectively reviewed the charts of all patients who had pregnancy-associated adnexal masses surgically removed at their institution over a 12-year period. They found the incidence of surgical resection of an adnexal mass in pregnancy to be 1 in 632 pregnancies. This number is within the range of previously published reports, which vary widely. They found a low rate of complications associated with surgical excision of these masses in either the immediate postoperative period or in the remainder of the patients’ antepartum courses. In only one case was surgery performed on an emergency basis as a result of adnexal torsion. Interestingly, they found a malignancy rate of 13%. This rate of ovarian cancer is twice the highest previously reported rate of 6%.4 Half of the cancerous masses were of low malignant potential. Both surgical resection of adnexal masses in pregnancy and expectant management of such masses carry with them their own set of problems. The risks of expectant, watchful management are 2-fold. First, there is the risk of torsion or rupture necessitating emergency intervention. Hess et al5 reported an increased risk of adverse pregnancy outcomes—40% spontaneous miscarriage or preterm birth—associated with emergency surgery for adnexal masses in pregnancy. Whitecar et al4 reported a risk of poor perinatal outcomes greater than 50% associated with laparotomy after 23 weeks gestation—an event that becomes more likely if expectant management is persued. Second, there is a risk of delayed diagnosis of malignancy. Ovarian cancer is the second most common gynecologic cancer diagnosed during pregnancy. Fortunately, ovarian malignancy is rare in pregnancy, reflecting the overall low rate of ovarian cancer in women of childbearing age. It is not surprising that ovarian cancers diagnosed in pregnancy are most commonly of low malignant potential or of germ cell origin because these match the prevalence of these tumors in similarly aged nonpregnant patients.6 However, such reassuring statistics may not be so comforting to patients who are told that they may have an ovarian malignancy. Attempts have been made to use noninvasive or minimally invasive techniques to differentiate benign and malignant lesions. Magnetic resonance imaging, color Doppler ultrasound, and aspiration cytology, while sometimes helpful in specific cases, have all been disappointing in providing adequate predictive power on which to base management decisions.7,8 The risks of active management of pregnancy-associated adnexal masses lie in the risk of surgical exploration itself. Although laparotomy or laparoscopy in a nonemergency setting has been shown to be fraught with fewer complications than emergency procedures or those in the second or third trimesters, adverse outcomes are not unknown in these patients.4,5 As clinicians, many if not all of us have been faced with this dilemma. Patients and their spouses are often equally afraid of the consequences of aggressive and conservative
Key words: Adnexal masses, malignancy, pregnancy
The number of adnexal masses diagnosed concurrently with pregnancy has increased as the routine use of ultrasonography has increased. The use of ultrasonography has resulted in the detection of asymptomatic and clinically inapparent lesions.1 Historically, adnexal masses were diagnosed on physical examination. Earlier diagnosis of pregnancy as a result of very sensitive home pregnancy tests and increased access to prenatal care may contribute to increased detection of pregnancy-associated masses. As more women enter into prenatal care at earlier gestational ages, the incidence of lesions increases as more functional cysts are detected. Currently, adnexal masses have been noted to occur in up to 1% of all gestations.1 The management of adnexal masses associated with pregnancy is variable. The two most common options are operative extirpation of the mass or expectant management. Cyst size, gestational age, and sonographic appearance all need to be considered when evaluating adnexal masses and formulating a treatment plan. Previous studies have both supported and refuted complications associated with these options of therapy. The histologic
From the Departments of Obstetrics and Gynecology,a and Pathology,b East Carolina University, Brody School of Medicine, Pitt County Memorial Hospital. Presented at Sixty-Fifth Annual Meeting of the South Atlantic Association of Obstetricians and Gynecologists, Hot Springs, Va, January 25-28, 2003. Reprint requests: Gordon B. Sherard III, MD, 201 Pineville Rd, Spartanburg, SC 29307. E-mail: [email protected] Ó 2003, Mosby, Inc. All rights reserved. 0002-9378/2003 $30.00 + 0 doi:10.1067/S0002-9378(03)00731-2
358
diagnoses most commonly reported for these persistent masses are functional cysts and mature cystic teratomas. The incidence of ovarian cancer associated with persistent adnexal masses in pregnancy varies, with reports as high as 5.9%.2 The purpose of this article was to characterize the adnexal masses associated with pregnancy at a tertiary care facility and to report on the maternal and fetal outcomes. The description of the mass will include clinical presentation, ultrasound morphologic features, and histologic diagnosis. Increased data on adnexal masses in pregnancy will enhance the counseling of patients regarding management options. Material and methods This was a retrospective study of all pregnancyassociated adnexal masses that were surgically resected at Pitt County Memorial Hospital, a tertiary care facility in rural eastern North Carolina from January 1990 through March 2002. The obstetric database was reviewed for exploratory laparotomy, operative laparoscopy, adnexal mass, and pelvic mass. The pathology database was also searched for adnexal, ovarian, or pelvic mass associated with pregnancy. Data collection included maternal age, race, gravidity, parity, gestational age at diagnosis, gestational age at surgery, gestational age at delivery, ultrasonographic findings, site of lesion, pregnancy complications, neonatal complications, birth weight, Apgar scores, and histologic diagnosis of the adnexal masses. Mean diameter of the mass was calculated as the sum of three diameters divided by 3. Term deliveries were defined as occurring after 37 weeks and up to 42 weeks of
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Table I. Maternal demographics (n = 56) Average maternal age Average gravidity Average parity Nulliparous Race African-American White Other Complications of pregnancy Diabetes Hypertension Asthma Sickle cell disease/trait Thyroid dysfunction Advanced maternal age Lupus erythematosus Rh negative (nonsensitized) Twins Tobacco use Pyelonephritis
Table II. Neonatal data (n = 42) 27 y 2.4 0.9 45%
(15-41y) (1-7) (0-5) (n = 25)
59% (n = 33) 36% (n = 20) 5% (n = 3) 9% 5% 2% 4% 2% 12.5% 2% 9% 3% 2% 2%
(n (n (n (n (n (n (n (n (n (n (n
= = = = = = = = = = =
5) 3) 1) 2) 1) 7) 1) 5) 3) 1) 1)
gestation and preterm deliveries were defined as occurring before 37 weeks of gestation. The decision on whether to operate was determined by the staff physician and/or maternal fetal medicine specialist. Microsoft Excel statistical software was used to preform two-tailed t tests on the mean cyst diameter. Results There were 37,929 deliveries during the study period. Sixty-three patients with adnexal masses were identified through our database searches. Of the 63 patients, 7 were lost to follow-up and not included in our study resulting in a final study group of 56 patients. After patients with bilateral disease were included, the total number of adnexal masses was 60, giving an incidence of 0.15% (1/632 pregnancies) in our series. Mean maternal age and parity were 27 years and 1, respectively (Table I). The mean gestational age at diagnosis of the adnexal mass was 12 weeks and the mean gestational age at surgery was 20 weeks. Fourteen cases (22%) were diagnosed during the first trimester at an average gestational age of 9 weeks (6-11 weeks). After documenting no spontaneous resolution, these masses were removed at an average gestational age of 17 weeks. During the 12th to 20th gestational week, 17 more masses were discovered at an average gestational age of 16 weeks (12-20 weeks). The average gestational age at surgery was 23 weeks for these masses. Thirty-one of the 56 (55%) study patients underwent surgery on or before completion of the 20th gestational week. The remainder had operations either at cesarean section or immediately post partum. Nine patients were followed up expectantly after diagnosis with the average length of antepartum follow-up lasting 17 weeks (range 7-26 weeks). Seventeen patients had masses removed at cesarean section and 5 patients had laparotomies in the immediate postpartum period.
Gestational age at delivery Term delivery Preterm delivery Spontaneous abortion Elective abortion Route of delivery Vaginal delivery Cesarean delivery Curettage Average birth weight Average Apgar score 1 min 5 min
37.5 ± 2.5 wk 69% (n = 29) 24% (n = 10) 4.7% (n = 2) 2.3% (n = 1) 44% (n = 19) 54% (n = 23) 2% (n = 1) 2877 ± 911 g 7.5 8.7
± 0.59 ± 0.19
Fifty-four operations (96%) were by laparotomy and the two most recent surgeries were laparoscopic procedures. Ninety-eight percent (55/56) of our cases were elective cases. One emergency surgery for adnexal torsion was preformed. Vertical midline incisions were used in the majority of the laparotomy cases. The two laparoscopic cases were preformed at 15 and 17 weeks gestation for one mature cystic teratoma and one functional cyst, respectively. Traditional pressure values of 15 mm Hg were used for insufflation. Neonatal information was only available for 42 of 56 patients (75%) as a result of patients returning to the referring physicians after evaluation and management of the adnexal mass. Term delivery occurred in 69% of patients. Preterm deliveries included two sets of twins and two inductions of labor for nonreassuring fetal status. Mean 1 and 5 minute Apgar scores were 7.5 and 8.7 (Table II). Fifty percent (30/60) of the lesions were mature cystic teratomas, 13% were functional ovarian cysts, and 20% were benign cystadenomas. The incidence of cancer associated with adnexal masses in pregnancy was 13%. Low malignant potential tumors comprised 63% (5/8) of malignant neoplasms, whereas the remaining 37% (3/8) displayed stromal invasion (Table III). The mean cyst size for nonmalignant masses was 7.6 cm (range 3 cm to 15cm) and 11.5 cm for malignant masses (range 6 cm to 17 cm). Septations were found equivalently in malignant and nonmalignant processes. Internal excrescences were found in 50% of malignant tumors and not in any benign lesions (Table IV). The Federation of International Gynecology and Obstetrics (FIGO) system was used to surgically stage the ovarian cancers. Cell washings, peritoneal biopsies, lymph node sampling, and partial omentectomies were performed. At diagnosis, all the cancers were FIGO stage IA. Maternal data for patients with ovarian cancer is presented in Table V. Ascites, a frequent coexisting condition with ovarian cancer, was detected by ultrasonography in two cases in our series. One case was a luteoma (functional cyst) and the other was an immature teratoma
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Table III. Adnexal mass pathology Histologic diagnosis
%
Mature cystic teratoma (n = 30) Cystadenoma (n = 12) Functional (n = 8) Cancer (n = 8)* Fibroma (n = 1) Paratubal (n = 1)
Table V. Ovarian cancer demographics Calculated mean cyst size (cm)
50 20 13 13 2 2
6.2 ± 2.1 11 ± 3.9 7.4 ± 3 11.5 ± 3.9 3 7
(3-11) (4-13) (4-13) (6-17)
*Four papillary serous, low malignant potential; 1 mucinous, low malignant potential; 2 immature teratomas; 1 dysgerminoma.
Table IV. Ultrasound data (n = 40)
Morphology Complex Solid Cystic Discriminator Internal excrescences Echogenic focus Septated
Benign (n = 32)
Malignant (n = 8)
66% (n = 21) 13% (n = 4) 22% (n = 7)
87.5% (n = 7) 12.5 (n = 1) 0%
0% 3% (n = 1) 9% (n = 3)
50% (n = 4) 0% 13% (n = 1)
that actually had an intact ovarian capsule at time of operation. The ultrasound was misleading because of the extremely large nature (>2 L) of the cystic component of the neoplasm. Comment In our large series of adnexal masses in pregnancy, we found the distribution of histology variable from other reports. Although the incidence of cystadenomas associated with adnexal masses in pregnancy was similar in our study compared with prior studies, we had several findings that differed from what had previously been reported. The 50% incidence of mature cystic teratomas in our series was increased over the previously reported 20% to 30% incidence. Functional cysts occurred in only 13% of our cases compared with previous ranges between 22% to 54%. The most striking finding in our series, however, was the increased incidence of malignancy in persistent adnexal masses in pregnancy. The 13% incidence is over twice the previously reported incidence of 2% to 6%.3 Pregnancy outcomes in our series are consistent with previous reports. The postoperative spontaneous abortion rate after elective removal was 4.6%. One emergency surgery was preformed in a patient at 20 weeks gestational age as a result of ovarian torsion; she was delivered uneventfully at term. The overall incidence of preterm birth was 24% (10/42). When adjusted for two pairs of twins and two inductions of labor for fetal indications, the rate of preterm delivery decreases to 9%.
Average maternal age Average gravidity Average parity Nulliparous Race African American White Site Right Left Bilateral
22 y 2.3 1 57%
(15-38y) (1-5) (0-3) (n = 4)
43% (n = 3) 57% (n = 4) 57% (n = 4) 29% (n = 2) 14% (n = 1)
Multiple authors have recommended conservative management of adnexal masses #6 cm. Grimes et al4 reported 185 adnexal masses; 111 cysts were diagnosed during pregnancy and expectantly managed. Ninety-two of 98 (94%) cysts that were less than 6 cm spontaneously resolved. These authors proposed that the pedicle is able to resist torsion as long as the cyst is not greater than 6 cm. A separate study reporting on 137 masses noted that 31 of 38 (82%) cysts less than 6 cm resolved.5 All cysts 5 cm or less resolved in the largest series that described 131 pregnancy-associated adnexal masses.6 In addition to the possibility of spontaneous cyst resolution, the decision to postpone surgery until after the first trimester has been based on cases described in the Emil Novak Tumor registry. One third of all surgeries preformed in the first trimester ended in spontaneous abortion in that series.7 These data are a common guideline for timing elective operative removal of adnexal masses in pregnancy. Expectant management has been associated with adverse pregnancy outcome if the mass undergoes torsion, rupture, or hemorrhage. Hess et al2 reported 15 of 54 (28%) patients with adnexal masses found in pregnancy required emergency laparotomy (6 acute hemorrhage, 7 cyst torsion). Of these patients requiring emergency surgery, 6 of 15 (40%) had adverse pregnancy outcomes postoperatively, four spontaneous abortions and two preterm births. Of the remaining 39 patients who had elective removal of an adnexal mass, only 1 (2%) had an adverse pregnancy outcome. Interestingly, seven cases in this series involved the removal of a corpus luteum, including five that had to have emergency surgery. Two patients had postoperative spontaneous abortions for an incidence of 29% (2/7). In our study, 2 of 42 (4.7%) patients with available delivery data had an adverse pregnancy outcome after elective removal of an adnexal mass. One patient had a spontaneous abortion immediately after surgery at 16 weeks. The other patient had premature rupture of membranes at 18 weeks after amniocentesis for advanced maternal age at 15 weeks and surgery at 15.3 weeks of gestation.
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The effect of pregnancy on mature cystic teratomas has also been evaluated and one study noted increased complications. Torsion occurred in 19% and rupture in 17% of these cysts in pregnancy.8 Because of the high incidence of adverse pregnancy outcomes in association with emergency surgery previously reported, some authors recommend elective removal of all masses that persist until 16 weeks and are 6 cm or greater regardless of appearance on imaging studies, unless it is suspected to be a leiomyoma.2 Conversely, torsion occurred in only 1 of 139 conservatively managed patients in the study by Grimes et al.4 At surgery, the ovarian pedicle was untwisted and a cystectomy was performed on a 10-cm cyst. The patient had no postoperative pregnancy-related complications. There were no complications in a study that expectantly followed up 49 patients with presumed dermoids. Pregnancy did not affect the growth of mature cystic teratomas 6 cm or less in these patients.9 Twelve patients were followed up, and there was no incidence of torsion in another study.10 In the 9 patients we managed conservatively with mature cystic teratomas (average cyst size 6.3 cm), torsion did not occur. The length of follow-up for these patients ranged from 7weeks to 26 weeks. Only 1 patient in our series was diagnosed with torsion (on initial presentation for care at 20 weeks’ gestation) and taken to the operating room. Postoperatively, she had no further antenatal complications and was delivered at term. Gross and microscopic examination to exclude a malignant neoplasm is an indication for operative intervention. The reported incidence of ovarian cancer in pregnancy ranges from 1:5000 to 1:47,000 live births with 2% to 6% of persistent adnexal masses being malignant.7,10 Tumors with low malignant potential and epithelial cancers are the most common ovarian cancers found in pregnancy.11 In our series, 13% (8/60) of persistent adnexal masses were malignant. The malignancy rate in our series was 1 in 4741 pregnancies. In agreement with a previously reported study describing ovarian cancer in pregnancy, the majority of cancers in our series were tumors of low malignant potential.12 Size has been used as an indicator for surgery in nonpregnant patients. Historic recommendations have been to remove masses that were larger than 8 cm or masses between 5 and 8 cm that did not resolve after 8 weeks in menstruating women.13 In our series, the average mean cyst size was 11.5 cm for malignant lesions and 11 cm for cystadenomas (P value not significant) (Table III). However, the average mean cyst size for all benign lesions was 7.6 cm (P value <.05). Thus, using size alone as an absolute discriminator does not appear to be predictive, unless the lesion is less than 6 cm. Ultrasound evaluation of adnexal masses has been utilized in the attempt to differentiate between malignant and benign tumors. Different evaluation techniques using
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weighted scoring systems (including septations, wall structure, and echogenicity) exist. The difficulty in differentiating certain benign conditions from malignancy has yielded positive predictive values around 30%.14 In another study, the ultrasound in 15% of the cases was ‘‘frankly misleading.’’15 Included were 6% of cases interpreted as benign when a malignancy was documented by histologic study. Twenty-two percent of ultrasonographic simple cysts were noted on pathologic examination to be low malignant potential tumors in a separate study.6 In our cases, 80% (4/5) of masses that were of low malignant potential had ultrasonographic morphologic features significant for papillary excrescences detected on the internal cyst wall. Solid tumors are another frequently cited reason for surgery over concerns for malignancy. Of the six solid tumors in our series, four (66%) were benign, including a luteoma, a fibroma, and two mature cystic teratomas. There were two malignancies (33%), an immature teratoma and a dysgerminoma (Table V). Color-flow Doppler imaging has also been used as an adjunct in evaluating adnexal masses. Building on the presence of neovascularization and the associated low resistance vessels (because of the absence of muscularis development) in malignancy, descriptions of pulsatility and resistance indices have been published.16 However, no such data have been reported for adnexal masses in pregnancy. Magnetic resonance imaging (MRI) is another imaging modality that has been used to assist in the characterization of adnexal masses. In one published study, magnetic resonance imaging (MRI) was used in the differentiation between solid ovarian masses and leiomyoma.17 More information and studies on the benefits of MRI are needed before its routine use in the work-p of pregnancyassociated adnexal masses. In summation, we found a much higher than expected malignancy rate. We postulate that as a regional center, our malignancy rate is higher because lesions that are smaller or more benign appearing are managed by private practitioners and not referred. Importantly, the size of the ovarian mass diagnosed in pregnancy was not absolutely predictive of malignancy. However, all masses less than 6 cm were noted to be benign. Morphologic study, as characterized by ultrasonography, detected internal papillary excrescences in 50% of malignancies in our series. Neonatal outcome was not adversely affected in either elective cases or our only emergency surgery. Our data support that of other published studies, to manage masses conservatively, performing surgery in the second trimester. We conclude that patients with persistent adnexal masses greater than 6 cm should undergo surgical removal, be appropriately counseled as to the possibility of an underlying malignancy, and be prepared for possible ovarian cancer staging.
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REFERENCES 1. Nelson MJ, Cavalieri R, Sanders RC. Cysts in pregnancy discovered by sonography. J Clin Ultrasound 1986;14:509-12. 2. Hess LW, Peaceman A, O’Brien WF, Winkel CA, Cruikshank DP, Morrison JC. Adnexal mass occurring with intrauterine pregnancy: report of fifty-four patients requiring laparotomy for definitive management. Am J Obstet Gynecol 1988;158:1029-34. 3. Liu JR, Lilja JF, Johnston C. Adnexal masses and ovarian cancer in pregnancy. In: Trimble EL, Trimble CL, editors. Cancer obstetrics and gynecology. Philadelphia: Lippincott-Williams & Wilkins; 1999. p. 239-48. 4. Grimes WH, Bartholomew RA, Colvin ED, Fish JS, Lester WM. Ovarian cyst complicating pregnancy. Am J Obstet Gynecol 1954;68:594-603. 5. Hogston P, Lilford RJ. Ultrasound study of ovarian cysts in pregnancy: prevalence and significance. BJOG 1986;93:625-8. 6. Thornton JG, Wells M. Ovarian cysts in pregnancy: does ultrasound make traditional management inappropriate. Obstet Gynecol 1987;69:717-21. 7. Novak ER, Lambrou CD, Woodruff JD. Ovarian tumors in pregnancy: an ovarian tumor registry review. Obstet Gynecol 1975;46:401-6. 8. Peterson WF, Prevost EC, Edmunds FT, Hundley JM, Morris FK. Benign cystic teratomas of the ovary. Am J Obstet Gynecol 1955;70:368-82. 9. Caspi B, Levi R, Appelman Z, Rabinerson D, Goldman G, Hagay Z. Conservative management of ovarian cystic teratoma during pregnancy and labor. Am J Obstet Gynecol 2000;182:503-5. 10. Platelek DN, Henderson CE, Goldberg GL. The management of a persistent adnexal mass in pregnancy. Am J Obstet Gynecol 1995;173:1236-40. 11. Ovarian Tumor Panel of the Royal College of Obstetricians and Gynecologists. Ovarian epithelial tumours of borderline malignancy: pathological features and current status. BJOG 1983;90:743-50. 12. Dgani R, Shoham Z, Atar E, Zosmer A, Lancet M. Ovarian carcinoma during pregnancy: a study of 23 cases in Israel between the years 1960 and 1984. Gynecol Oncol 1989;33:326-31. 13. Droegemueller W. Benign gynecological lesions. In: Mishell DR, Stenchever MA, Droegemueller W, Herbst AL, editors. Comprehensive gynecology. 3rd ed. St. Louis: Mosby; 1997. p. 467-516. 14. Lerner JP, Timor-Tritsch IE, Federman A, Abramovich G. Transvaginal ultrasonographic characterization of ovarian masses with an improved, weighted scoring system. Am J Obstet Gynecol 1994;170:81-5. 15. Benacerraf BR, Finkler NJ, Wojciechowski C, Knapp RC. Sonographic accuracy in the diagnosis of ovarian masses. J Reprod Med 1990;35:491-5. 16. Fleischer AC, Kepple DM. Color Doppler sonography of pelvic masses. In: Fleischer AC, Manning FA, Jeanty P, Romero R, editors. Sonography in obstetrics and gynecology. 6th ed. New York: McGrawHill; 2001. p. 913-47. 17. Curtis M, Hopkins MP, Zarlingo T, Martino C, Graciansky-Lengyl M, Jenison EL. Magnetic resonance imaging to avoid laparotomy in pregnancy. Obstet Gynecol 1993;82:833-6.
Discussion DR JERRY F. MATKINS JR, Gastonia, NC. The detection of adnexal masses in pregnancy has become increasingly more common, and therefore the dilemma of how to manage these patients has become one that is faced more frequently. In the era before ultrasound, when palpation was relied on to diagnose adnexal masses, the detection rate was reported to be 1 in 591 pregnancies.1 By 1986, as ultrasound became more commonly used, the reported incidence of adnexal masses in pregnancy was 1 in 190.2 Because ultrasound has become more precise over the past 15 years, that detection rate has climbed to as high as one mass detected in every 50 pregnancies.3 Certainly all of these lesions are not clinically significant, so we cannot say with assurance that our increased technologic capabilities have resulted in better management of patients. In fact, we may have only succeeded in raising
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anxiety levels. It is in addressing the question of whether what we can now detect is truly significant, and if so when, that studies such as Dr Sherard’s are helpful. The authors retrospectively reviewed the charts of all patients who had pregnancy-associated adnexal masses surgically removed at their institution over a 12-year period. They found the incidence of surgical resection of an adnexal mass in pregnancy to be 1 in 632 pregnancies. This number is within the range of previously published reports, which vary widely. They found a low rate of complications associated with surgical excision of these masses in either the immediate postoperative period or in the remainder of the patients’ antepartum courses. In only one case was surgery performed on an emergency basis as a result of adnexal torsion. Interestingly, they found a malignancy rate of 13%. This rate of ovarian cancer is twice the highest previously reported rate of 6%.4 Half of the cancerous masses were of low malignant potential. Both surgical resection of adnexal masses in pregnancy and expectant management of such masses carry with them their own set of problems. The risks of expectant, watchful management are 2-fold. First, there is the risk of torsion or rupture necessitating emergency intervention. Hess et al5 reported an increased risk of adverse pregnancy outcomes—40% spontaneous miscarriage or preterm birth—associated with emergency surgery for adnexal masses in pregnancy. Whitecar et al4 reported a risk of poor perinatal outcomes greater than 50% associated with laparotomy after 23 weeks gestation—an event that becomes more likely if expectant management is persued. Second, there is a risk of delayed diagnosis of malignancy. Ovarian cancer is the second most common gynecologic cancer diagnosed during pregnancy. Fortunately, ovarian malignancy is rare in pregnancy, reflecting the overall low rate of ovarian cancer in women of childbearing age. It is not surprising that ovarian cancers diagnosed in pregnancy are most commonly of low malignant potential or of germ cell origin because these match the prevalence of these tumors in similarly aged nonpregnant patients.6 However, such reassuring statistics may not be so comforting to patients who are told that they may have an ovarian malignancy. Attempts have been made to use noninvasive or minimally invasive techniques to differentiate benign and malignant lesions. Magnetic resonance imaging, color Doppler ultrasound, and aspiration cytology, while sometimes helpful in specific cases, have all been disappointing in providing adequate predictive power on which to base management decisions.7,8 The risks of active management of pregnancy-associated adnexal masses lie in the risk of surgical exploration itself. Although laparotomy or laparoscopy in a nonemergency setting has been shown to be fraught with fewer complications than emergency procedures or those in the second or third trimesters, adverse outcomes are not unknown in these patients.4,5 As clinicians, many if not all of us have been faced with this dilemma. Patients and their spouses are often equally afraid of the consequences of aggressive and conservative