Adnexal Masses in Pregnancy

Home , Luteoma, Ovarian cystadenoma

A guide to management Mitchel S. Hoffman, MD Professor and Director, Division of Adnexal masses in pregnancy Gynecologic Oncology, Department of Obstetrics and Gynecology, Forego surgery in most cases until delivery—or until University of South Florida, Tampa, Fla Robyn A. Sayer, MD the risky fi rst trimester has passed Assistant Professor, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, CASE 1 An enlarging cystic tumor 16 × 12 × 4 cm and determined that it University of South Florida, Tampa, Fla was a corpus luteum cyst. The authors report no fi nancial relationships relevant to this article. A 20-year-old gravida 3 para 1011 visits the emergency department with persistent right Presence of mass raises questions ﬂ ank pain. Although ultrasonography (US) Despite the rarity of malignancy, the dis- shows a 21-week gestation, the patient has covery of an ovarian mass during pregnan- had no prenatal care. Imaging also reveals a® Dowdency prompts several Health important Media questions: right-sided ovarian tumor, 14 × 11 × 8 cm, How should the mass be assessed? How that is mainly cystic with some internal can the likelihood of malignancy be deter- echogenicity. CopyrightFor personalmined as quickly use and only effi ciently as pos- At 30 weeks’ gestation, a gynecologic sible, without jeopardy to the pregnancy? oncologist is consulted. Repeat US reveals When is surgical intervention warranted? the mass to be about 20 cm in diameter and And when can it be postponed? Specifi - cystic, without internal papillation. The pa- cally, is elective operative intervention for IN THIS ARTICLE tient’s CA-125 level is 12 U/mL. Based on this a tumor that is probably benign appro- information, the physicians decide the likely priate during pregnancy? ❙ The most common ﬁ nding is a benign ovarian cystadenoma. When is the best time to operate? And masses detected How should they proceed? what is the optimal surgical route? during pregnancy In this article, we address these ques- Page 28 he discovery of an adnexal mass tions with a focus on intervention. As we’ll during pregnancy isn’t as rare explain, only a small percentage of gravidas ❙ When you discover Tas you might think—depending who have an adnexal mass require surgery a mass during on when and how closely you look, it during pregnancy. When surgery is neces- occurs in about 1 in 100 gestations. In sary, it is usually indicated for an emergent cesarean section most cases, we have found, the mass is problem or suspicion of malignancy. Even Page 32 clearly benign (TABLE 1, page 32), war- when ovarian cancer is confi rmed, we have ranting only observation. found that it is usually in its early stages ❙ Laparoscopy In the case described above, the phy- and therefore has a favorable prognosis or laparotomy? sicians followed the patient and removed (TABLE 2, page 32). Page 43 the mass at term because it was cystic with no other indications of malignancy. At 37 weeks’ gestation, a cesarean section How should a mass was performed through a midline lapa- be assessed? rotomy incision, followed by removal of Ultrasonography and other imaging of- the ovarian tumor, which was benign. ten reveal the presence of a mass and help The pathologist measured the tumor at determine whether it is benign or malig- CONTINUED www.obgmanagement.com March 2007 • OBG MANAGEMENT 27

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Common adnexal tumors found during pregnancy

Corpus luteum Benign cystadenoma A persistent corpus luteum is a normal component In an asymptomatic patient with imaging that sug- of pregnancy. Although it usually appears as a small gests a benign cystadenoma (see sonogram below, cystic structure on ultrasonographic imaging, the left), benign cystic teratoma, or other benign tumor, corpus luteum of pregnancy can reach 10 cm in observation is reasonable in most cases.4,6,7,9–11,14,19 size. Other types of “functional” ovarian cysts may Operative intervention is required when there is less also be found during pregnancy. Most functional certainty regarding the benign nature of the tumor, cysts resolve by the early second trimester.4,6 In rare an acute complication develops, or the tumor is cases, a cyst may develop complications such as expected to pose problems because of its large torsion or rupture, causing acute pain or hemor- size alone. rhage. Otherwise, a cystic tumor identifi ed in the fi rst trimester should be characterized and followed Uterine leiomyoma using ultrasonography (US). It is rare for an ovarian tumor detected during pregnancy to have a solid appearance on US. When it Benign neoplasm does, it may be a uterine leiomyoma mimicking an An adnexal mass that persists beyond the fi rst adnexal tumor (see intraoperative photograph trimester is more likely to be a neoplasm.3–5,10,11,22 below, right). It should be reevaluated with more Such a mass is generally considered clinically detailed US or magnetic resonance imaging.25 signifi cant if it exceeds 5 cm in diameter and has a complex sonographic appearance. Usually such a Malignancy neoplasm will be a benign cystadenoma or cystic About 10% of adnexal masses that persist during teratoma. 5,10–13,19,23,24 pregnancy are malignant, according to recent series.4,5,7–10,12,13,24,26 Benign cystic teratoma Most of the ovarian cancers diagnosed during This tumor can be identifi ed with a fairly high degree pregnancy are epithelial, and a substantial portion of of specifi city using a variety of imaging techniques, these are low-malignant-potential (LMP) with management based on the presumptive diagno- tumors.5,10,11,13,19,23,24,26,27 This ratio is in keeping with sis. This tumor is unlikely to grow substantially during the age of these women, which also explains the pregnancy. When it is smaller than 6 cm, such a tumor stage distribution (most are stage 1) and the large can simply be observed.14 A larger tumor can oc- percentage of germ-cell tumors detected. The major- casionally rupture or lead to torsion or obstruction of ity of ovarian cancers discovered in pregnant women labor, but such occurrences are rare. have a favorable prognosis.

Benign-appearing cystadenoma Leiomyoma mimics an ovarian tumor

UT CYST

A morphologically benign-appearing, large, cystic adnexal mass can be This 17-week gestation was marked by a large pedunculated leiomyoma seen in association with an 11-week gestation. that at fi rst appeared to be a right adnexal tumor.

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TABLE 1 Appearance of adnexal masses on US Adnexal masses removed during A functional cyst such as a follicular cyst, pregnancy: Histologic proﬁ le corpus luteum cyst, or theca lutein cyst usually has smooth borders and a fl uid HISTOLOGIC TYPE NUMBER (%) center. Other cysts may sometimes con- Cystadenoma 549 (33) tain debris, such as clotted blood, that Dermoid 451 (27) suggests endometriosis or a simple cyst with bleeding into it. Paraovarian/paratubal 204 (12) A benign cystic teratoma often has mul- Functional 237 (14) tiple tissue lines, evidence of calcifi cation, Endometrioma 55 (3) and layering of fat and fl uid contents. A benign cystadenoma usually has the Benign stromal 28 (2) appearance of a simple cyst without Leiomyoma 23 (1.5) large septates, whereas a cystadenocar- Luteoma 8 (0.5) cinoma often contains septates, abnor- mal blood fl ow, increased vascularity, or Miscellaneous 55 (3) all of these. However, it is impossible to Malignant 68 (4) defi nitively distinguish a cystadenoma Total 1,678 from a cystadenocarcinoma using US

Data supplied by the authors from surgical experience imaging alone. Functional cysts usually resolve by the second trimester. A cyst warrants TABLE 2 closer scrutiny when it persists, is larger Malignant adnexal masses than 5 cm in diameter, or has a complex removed during pregnancy appearance on US. HISTOLOGIC TYPE NUMBER (%) CA-125 may be useful Epithelial 101 (28) after the ﬁ rst trimester FAST TRACK Borderline epithelial 147 (40) The serum CA-125 level is typically elevated during the fi rst trimester, but may The serum CA-125 Germ-cell dysgerminoma 47 (13) be useful during later assessment or for level is typically Other 34 (9) follow-up of a malignancy.1 elevated during the Stromal 24 (7) A markedly elevated serum level of ﬁ rst trimester, but alpha-fetoprotein (fractionated in some Undifferentiated 5 (1.4) may be useful for cases) has been reported in some gravi- Sarcoma 2 (0.5) das with an endodermal sinus or mixed assessment later in 2 pregnancy Metastatic 4 (1.1) germ-cell ovarian tumor. Alpha-feto- Total 364 protein should be measured when there is suspicion for a germ-cell tumor based Data supplied by the authors from surgical experience on clinical or US fi ndings.

nant. In fact, most adnexal masses dis- When a mass is discovered covered during pregnancy are incidental during cesarean section fi ndings at the time of routine prenatal Occasionally, an adnexal mass is de- US. (See page 28 for the most commonly tected at the time of cesarean section found tumors.) Operative intervention is (FIGURE 1, page 34).3 This phenomenon required in 3 situations: is increasingly common, given the large • malignancy is suspected number of cesarean deliveries in the Unit- • an acute complication develops ed States. To eliminate the need for future • the sheer size of the tumor is likely to surgery and avoid a delay in the diagno- cause diffi culty. sis of an ovarian malignancy, inspect the

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FIGURE 1 eral ways. For example, surgical stag- Mass discovered ing of clinically early ovarian cancer is at cesarean section more diffi cult due to the pregnant uterus, which is more extensively manipulated during these procedures. In addition, an optimal operation sometimes necessitates removal of the uterus. At 13 weeks’ gestation, the patient described in case 2 underwent laparoscopy with peritoneal washings and left salpin- go-oophorectomy, but the tumor ruptured during removal. Final pathology showed it to be a serous LMP tumor involving the surface of the left ovary. Washings were in line with this diagnosis.

This cystic tumor was discovered at cesarean section that The pregnancy continued unevent- was undertaken for obstetric indications. fully, and a repeat cesarean section was performed at 37 weeks through the adnexa routinely after closing the uterine Pfannenstiel scar, followed by limited incision in all women who deliver by ce- surgical staging. Exploration and all bi- sarean section. opsies were negative, and the fi nal diagnosis was a stage 1C serous LMP tumor CASE 2 LMP tumor is suspected of the ovary. The patient articulated a desire to A 36-year-old gravida 3 para 1011 makes preserve her fertility and was monitored a prenatal visit during the ﬁ rst trimester. with US imaging of the remaining ovary Her previous delivery was a cesarean sec- every 6 months. tion through a Pfannenstiel incision for a FAST TRACK breech presentation. US imaging reveals Does ‘indolent’ behavior of Some ovarian a 6-week, 5-day fetus and a complex left malignancy justify watchful waiting? adnexal mass, 4.5 × 3.9 × 4.1 cm. Imaging LMP tumors comprise a relatively large cancers may is repeated 1 month later at a tertiary-care percentage of ovarian “cancers” en- present acutely, such center and shows an 11-week viable fetus, countered during pregnancy. Some au- as a rapidly growing a right ovary with a corpus luteum cyst, thors report the accurate identifi cation germ-cell tumor and a left ovary with a 6.6 x 4 cm cystic of these tumors prospectively, based on or a ruptured and mass with extensive vascular surface ultrasonographic characteristics.4,5 When papillations that is suspicious for a low- an LMP tumor is the likely diagnosis, se- hemorrhaging malignant-potential (LMP) tumor. In several rial observation during pregnancy may granulosa-cell tumor sonograms prior to the pregnancy, this be appropriate because of the indolent mass appeared to be solid and was 3 cm nature of the tumor. Further studies are in size. needed to refi ne preoperative diagnosis and determine the overall safety of this approach. When is surgery warranted? Surgery is indicated when physical ex- When the problem is acute amination or imaging of a pregnant In rare cases, a pregnant patient will have woman reveals an adnexal mass that is (or develop during observation) an acute suspicious for malignancy, but the phy- problem due to torsion or rupture of sician must weigh the benefi t of prompt an adnexal mass. Some ovarian cancers surgery against the risk to the pregnancy. may present acutely, such as a rapidly This equation can be complicated in sev- growing malignant germ-cell tumor or a CONTINUED

34 OBG MANAGEMENT • March 2007 Adnexal masses in pregnancy

ruptured and hemorrhaging granulosa- Integrating evidence and experience cell tumor. Emergent surgery is necessary to manage the acute adnexal disease and Pregnant women have a very reduce the likelihood of pregnancy loss. low rate of ovarian cancer These events are infrequent, occurring in Leiserowitz GS, Xing G, Cress R, Brahmbhatt B, Dalrymple JL, Smith LH. less than 10% of women with a known, Adnexal masses in pregnancy: how often are they malignant? Gynecol Oncol. persistent adnexal mass during pregnan- 2006;101:315–321. 4–14 cy. Furthermore, recent studies have varian malignancies are rare during pregnancy. When not found a substantial pregnancy com- they do occur, they are likely to be early stage and to plication rate associated with such emer- O have a favorable outcome, according to this recent gency surgeries. population-based study. Using 3 large databases containing records on 4,846,505 CASE 3 Suspicious mass, ascites California obstetric patients between 1991 and 1999, Leiserowitz signal need for surgery and colleagues identifi ed 9,375 women who had an ovarian mass associated with pregnancy. Of these, 87 had ovarian A 19-year-old gravida 1 para 0 seeks cancer and 115 had a low-malignant-potential (LMP) tumor, for a cancer occurrence rate of 0.93%, or 0.0179 per 1,000 deliveries. prenatal care at 17 weeks’ gestation, Thirty-four of the 87 cancers were germ-cell tumors. complaining of rapidly enlarging abdominal Of the 87 ovarian cancers, 65.5% were localized, 6.9% girth. The physical examination estimates regional, 23% remote, and 4.6% of unknown stage. The gestational size to be considerably greater respective rates for LMP tumors were 81.7%, 7.8%, 4.4%, and than dates, but US is consistent with a 17- 6.1%. week intrauterine pregnancy. Imaging also Women with malignant tumors were more likely than reveals a 12-cm heterogenous left adnexal pregnant controls without cancer to undergo cesarean delivery, mass and a large amount of ascites. hysterectomy, transfusion, and prolonged hospitalization. Surgery is clearly warranted, but how These women did not, however, have a higher rate of adverse extensive should it be? neonatal outcomes.

When a malignancy is detected, a thor- In case 3, a laparotomy was per- ough staging procedure may be justifi ed, formed at 19 weeks’ gestation via a depending on gestational age, exposure, midline incision, and approximately desires of the patient, and operative fi nd- 5.3 L of ascites was evacuated. A large, ings. A midline incision is preferred. nonadherent left ovarian tumor was re- Pregnant and nonpregnant women moved. The right ovary appeared to be with stage 1A or 1C epithelial ovarian normal, as did the gravid uterus, which cancer who undergo fertility-preserving was minimally manipulated. The rest surgery (with chemotherapy in selected of the surgical exploration was normal, patients) have a good prognosis and a and the distal portion of the omentum high likelihood of achieving a subsequent was excised. The frozen-section diag- normal pregnancy.15 The same is true nosis was a malignant stromal tumor. for women with a malignant germ-cell Final pathology showed an 18 × 13.5 tumor of the ovary, even when disease × 8.8 cm, poorly differentiated, Sertoli- is advanced.16 However, careful surgical Leydig-cell tumor with heterologous staging is necessary. elements in the form of mucinous epi- The most important consideration thelium. The omentum was negative for when deciding whether to continue the tumor. pregnancy is the need for adjuvant che- Chemotherapy was initiated in the motherapy. Depending on the gestational third trimester, based on the limited age and diagnosis, a short delay (4 to 6 data available, with intravenous etopo- weeks) may be appropriate to allow the side and platinum administered every pregnancy to progress beyond the fi rst 21 days. The patient received 3 cycles trimester or to maturity. of chemotherapy prior to delivery. CONTINUED www.obgmanagement.com March 2007 • OBG MANAGEMENT 39 Adnexal masses in pregnancy

Integrating evidence and experience diagnosis. As always, the patient’s wishes Can surgery be delayed and gestational age must be considered. when a mass is detected? How factors besides malignancy Schmeler KM, Mayo-Smith WW, Peipert JF, Weitzen S, Manuel MD, Gordinier ME. can inﬂ uence care Adnexal masses in pregnancy: surgery compared with observation. Obstet Gynecol. Most persistent adnexal masses move 2005;105:1098–1103. well out of the pelvis as pregnancy pro- lose observation is a reasonable alternative to operative gresses. Occasionally, however, an ovari- intervention during pregnancy, unless a malignancy is an tumor may be located in the posterior C suspected. cul-de-sac even at term, a fact easily con- Schmeler and colleagues reviewed the cases of 59 women fi rmed by examination or US.4,7 A tumor who had an adnexal mass larger than 5 cm in diameter in the posterior cul-de-sac can obstruct detected during pregnancy, out of a total of 127,177 deliveries delivery or rupture. When it has a benign at a single institution between 1990 and 2003. Antepartum cystic appearance on US, it may be de- surgery was performed in 17 women (29%). Of these, 13 compressed via transvaginal aspiration. cases had ultrasonographic fi ndings suggesting malignancy, Otherwise, the best approach is cesarean and 4 had ovarian torsion. The remaining women were section and concomitant management of observed, with surgery delayed until the time of cesarean the mass. section or later. Twenty-fi ve of the 59 masses (42%) were dermoid cysts. Cancer was diagnosed in 4 patients (6.8%), and 1 patient When size alone is the problem (1.7%) had an LMP tumor. All 5 cases (100%) involving a Some ovarian tumors are so large they malignancy had a suspicious US appearance and were seem incompatible with an advancing identifi ed during antepartum surgery, whereas only 12 patients pregnancy. Tumors up to 20 cm in di- with a benign tumor (22%) underwent surgery prior to delivery. ameter have been removed intact at the time of cesarean section (FIGURE 2, page 43).18 The tumor may accommodate in At 37 weeks’ gestation, labor was shape and become less problematic as it successfully induced. After delivery, bleo- is gradually pushed into the upper ab- mycin was added to the chemotherapy domen (FIGURE 3, page 43). regimen, and 3 additional courses with The ability of the peritoneal cavity all 3 agents were administered. The pa- to accommodate a tumor varies greatly tient was lost to follow-up shortly after among women. As pregnancy advances, completing chemotherapy. the likelihood that a large cystic mass will Clearly, an informed discussion of rupture tends to increase. Depending on the options with the patient is imperative the circumstances, percutaneous aspira- before any surgery, especially when che- tion7,18 or removal of a benign-appearing motherapy may be delayed. Pregnancy cystic tumor may be appropriate. does not appear to alter the prognosis for the patient with an ovarian malignancy, and ovarian cancer has not been reported When is the best time to metastasize to the fetus. to operate? Surgery is generally not recommended When cancer is advanced during the fi rst trimester.5–11 Among the Few data shed light on whether a preg- reasons are the high likelihood of a cor- nancy should continue when ovarian can- pus luteum cyst, the low likelihood of an cer is advanced.17 The defi nitive surgical invasive malignancy, the low risk of ad- approach must be highly individualized. nexal complications associated with ob- It is not always possible to make an servation, and the potential for pregnancy accurate diagnosis based on a frozen sec- loss or teratogenicity. However, as preg- tion. In such a case, the pregnancy should nancy progresses beyond the fi rst trimes- be preserved until the time of defi nitive ter, surgery poses other problems: Opera-

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tive exposure diminishes and the need to FIGURE 2 manipulate the pregnant uterus increases. Even a very large tumor may coexist with advancing pregnancy Surgery poses risks to the pregnancy Elective surgery for an adnexal mass any time during pregnancy increases the risk of pregnancy loss and the likelihood of intrauterine growth restriction (IUGR) and preterm delivery.5,7,10,13,19 A 1989 study from Sweden20 defi ned a cohort of 5,405 women (from 720,000 births) who were known to have a nonobstetric operation while pregnant, with the following results: • Congenital malformation and still- birth were not increased in the women undergoing surgery This benign serous cystadenoma was exteriorized at the • The number of very-low- and low- time of cesarean section at term. birth-weight infants did rise, however—the result of both prematurity FIGURE 3 and IUGR Large ovarian tumor has • Also elevated was the incidence of in- accommodated to the pregnancy fants born alive but dying within 168 hours; these risks increased regardless of trimester • No specifi c type of anesthesia or operation was associated with adverse reproductive outcomes, and the cause of those adverse outcomes was not determined. FAST TRACK Some recent data suggest that adnex- During the ﬁ rst and al surgery during the late second or early third trimester poses the greatest risk of second trimesters, preterm delivery or IUGR, or both.13 laparoscopy is as

Laparotomy—performed at term for cesarean section and safe as laparotomy Window of opportunity: to manage this large tumor—revealed that the tumor had accommodated in shape between the enlarging pregnant early to mid- second trimester uterus and the abdominal wall. During this time frame, elective surgery for an adnexal mass still affords some with cesarean delivery in general, the type pelvic exposure without the need for of skin incision (a vertical incision is appro- signifi cant uterine manipulation and has priate in the event of ovarian malignancy), been associated with a lower risk of preg- the potential for better exposure or lapa- nancy complications. roscopy at a later date, the increased dif- The other window for operation is at fi culty of ovarian cystectomy at the time of the time of cesarean section. An elective cesarean section, and the patient’s wishes. cesarean section is sometimes performed specifi cally to manage a persistent adnexal mass. Among the factors that warrant Laparoscopy or laparotomy? consideration when contemplating this The data on laparoscopy during the fi rst approach are the elective uterine incision and second trimesters of pregnancy in- (with its attendant implications for future dicate that it is as safe as laparotomy. A pregnancies), the higher risks associated 1997 Swedish study21 identifi ed cohorts

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of 2,181 women undergoing laparoscopy 6. Bernhard LM, Klebba PK, Gray DL, Mutch DG. Predic- tors of persistence of adnexal masses in pregnancy. and 1,522 women undergoing laparoto- Obstet Gynecol. 1999;93:585–589. my (from a total of 2,015,000 deliveries) 7. Platek DN, Henderson CE, Goldberg GL. The management of a persistent adnexal mass in pregnancy. Am J between the fourth and 20th weeks of Obstet Gynecol. 1995;173:1236–1240. pregnancy. In both groups there was an 8. Bromley B, Benacerraf B. Adnexal masses during increased risk for the infant to weigh less pregnancy: accuracy of sonographic diagnosis and outcome. J Ultrasound Med. 1997;16:447–452. than 2,500 g, to be delivered before 37 9. Hill LM, Connors-Beatty DJ, Nowak A, Tush B. The role weeks, and to have IUGR. There were no of ultrasonography in the detection and management of adnexal mass during the second and third trimesters of differences between the 2 groups for these pregnancy. Am J Obstet Gynecol. 1998;179:703–707. and other adverse outcomes. 10. Agarwal N, Parul, Kriplani A, Bhatla N, Gupta A. Manage- ment and outcome of pregnancies complicated with ad- Small series of laparoscopic proce- nexal masses. Arch Gynecol Obstet. 2003;267:148–152. dures to manage an adnexal mass during 11. Schmeler KM, Mayo-Smith WW, Peipert JF, Weitzen S, Manuel MD, Gordinier ME. Adnexal masses in preg- pregnancy suggest that this approach is nancy: surgery compared with observation. Obstet most applicable during the fi rst (for high- Gynecol. 2005;105:1098–1103. ly selected emergent cases) or early sec- 12. Coenen VH, Dunton C, Cardonick E, Berghella V. Per- sistent adnexal masses during pregnancy. Obstet Gy- ond trimester to manage masses less than necol. 1999;93:66S. 10 cm in diameter, particularly when ad- 13. Whitecar P, Turner S, Higby K. Adnexal masses in pregnancy: a review of 130 cases undergoing surgical nexectomy is planned. management. 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