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Adnexal mass: Evaluation and management in pregnancy

Adnexal mass: Evaluation and management in pregnancy
Literature review current through: May 2024.
This topic last updated: Jul 18, 2023.

INTRODUCTION — The liberal use of prenatal ultrasound for evaluation of the fetus has also resulted in increased detection of asymptomatic adnexal masses during pregnancy. Although the vast majority of these masses are benign, the possibility of cancer must be considered.

This topic will discuss management of the adnexal mass in pregnancy, with an emphasis on patients with suspected malignancy. Detailed reviews on the evaluation and management of the nonpregnant patient with an adnexal mass can be found separately:

(See "Approach to the patient with an adnexal mass".)

(See "Adnexal mass: Differential diagnosis".)

PREVALENCE — The incidence of adnexal masses complicating pregnancy varies from 0.05 to 2.4 percent, and approximately 1 to 6 percent of these masses are malignant [1-4]. A review of publications on ovarian cancer during pregnancy from 1958 to 2007 included 41 cases [5]. The mean age at presentation was 32.6 years (range 23 to 46 years); stage at diagnosis was recorded in 39 cases: International Federation of Gynecology and Obstetrics (FIGO) I (59 percent), FIGO II (5 percent), FIGO III (26 percent), and FIGO IV (10 percent). It is important to remember that the use of obstetric ultrasound and cesarean birth were much less common in the initial decades of this interval, thus there was less opportunity for incidental detection of asymptomatic adnexal masses.

In a population-based hospital registry series of malignancies identified during pregnancy using birth records linked to hospital discharge data (1992 to 1997), ovarian cancer was the fifth most common cancer diagnosed during pregnancy after breast, thyroid, cervical cancer, and Hodgkin lymphoma [2,6]. There was also a high proportion of tumors of low malignant potential (n = 115) reported separately, with the majority in early stage and associated with favorable maternal and neonatal outcomes. A retrospective review reported that ovarian cancer was the sixth most common cancer in patients from Korea [6].

PATIENT PRESENTATION — Prior to the widespread use of ultrasound, most adnexal masses in pregnant patients remained unrecognized until cesarean birth or until they became symptomatic, usually in the postpartum period. Now many asymptomatic masses are recognized in the first half of pregnancy when they are identified incidentally during an antenatal ultrasound performed for obstetric indications [1,5,7,8]. Adnexal masses that have not been diagnosed antepartum may be identified at cesarean birth. In a retrospective study of over 46,500 term cesarean deliveries performed for obstetric indications, 151 patients (0.3 percent) underwent concurrent surgery of an adnexal mass, which was an incidental finding at surgery in just over half of the patients (83 of 151; 55 percent) [9].

Other clinical presentations include:

Nonspecific symptoms – Symptoms and signs that precede the diagnosis of ovarian cancer include abdominal or back pain, constipation, abdominal swelling, and urinary symptoms [10,11]. Since these symptoms are almost universally present in normal pregnancies, their presence is unlikely to trigger a diagnostic evaluation.

Palpable mass – In some patients, a suspicious finding, such as a palpable adnexal mass or posterior cul-de-sac mass or nodularity, may be identified during a routine antenatal physical examination and subsequently evaluated by ultrasound.

Acute abdominal pain – In a few patients, acute abdominal pain due to torsion of the adnexa prompts the diagnostic evaluation. Adnexal torsion occurs in approximately 5 percent of pregnant patients with an adnexal mass (benign or malignant) [1]. In one review, adnexal masses between 6 and 8 cm in diameter had a significantly higher rate of torsion (22 percent) than either smaller or larger masses [12]. Sixty percent of the torsions occurred between the 10th and 17th week of gestation; only 6 percent occurred after 20 weeks. (See "Ovarian and fallopian tube torsion".)

Elevated maternal analytes – Many germ cell and sex cord-stromal tumors of the ovary produce hormonal tumor markers, some of which are measured in prenatal screening programs for fetal abnormalities (eg, alpha-fetoprotein [AFP], inhibin A) (table 1) [13]. An unexplained elevation in these maternal serum analytes, obtained while screening for neural tube defects or Down syndrome, may be the first sign of one of these tumors [13]. (See 'Tumor markers in ovarian malignancy' below.)

TYPES OF ADNEXAL MASSES IN PREGNANT PATIENTS — In a review of seven studies, there were 563 adnexal masses in 557 patients. Of these, 48 percent were classified as simple and 53 percent as complex. Among the simple masses, 1 percent were malignant whereas in the complex masses, 9 percent were malignant [3]. In another retrospective study of 151 patients who underwent surgery of an adnexal mass at cesarean birth, the adnexal mass was benign in 148 cases. Histopathologies accounting for over 4 percent of cases in the series included dermoid (24 percent), paratubal/paraovarian (19 percent), simple serous (15 percent), mucinous cystadenoma (11 percent), serous cystadenoma (7 percent), corpus luteum (5 percent), endometrioma (5 percent), and fibroma (5 percent) [9]. The three malignancies in the series consisted of two granulosa cell tumors and one mucinous carcinoma.

Benign neoplasms — Most adnexal masses identified in pregnant patients are benign simple cysts less than 5 cm in diameter. Most of these are functional ovarian cysts, either follicular or corpus luteum cysts, that occur as part of the normal physiological function of the ovary. Approximately 70 percent of all adnexal cystic masses detected in the first trimester spontaneously resolve by the early part of the second trimester, which is consistent with the natural history of functional cysts [7]. The majority of persistent adnexal masses 5 cm or greater in diameter are mature teratomas [1].

The differential diagnosis of the adnexal mass is reviewed in detail separately (see "Adnexal mass: Differential diagnosis"). Briefly, benign adnexal masses are characterized by their ultrasonographic appearance and, in some cases, associated clinical findings (see "Adnexal mass: Ultrasound categorization"):

Benign masses without complex features on ultrasound are generally physiologic/functional cysts (eg, follicular cysts), but may be unilocular serous or mucinous cystadenoma or hydrosalpinx.

Benign masses with complex features on ultrasound include corpus luteum, mature teratomas, hydrosalpinx with septation, theca lutein cysts, endometriomas, multilocular cystadenomas, as well as extrauterine pregnancies [14]. The corpus luteum persists longer during pregnancy and thus is likely to reach a larger size and may become hemorrhagic, rupture, or undergo torsion.

Theca lutein cysts (also called lutein cysts, hyperreactio luteinalis) are luteinized follicle cysts that form as a result of overstimulation from high human chorionic gonadotropin (hCG) levels or hypersensitivity to hCG. Bilateral multiseptated cystic adnexal masses in a patient with gestational trophoblastic disease, multiple gestation, ovulation induction, or a pregnancy complicated by fetal hydrops are likely to represent theca lutein cysts.

A luteoma is an uncommon solid benign lesion specific to pregnancy. It is a non-neoplastic ovarian change associated with pregnancy that can simulate a neoplasm on clinical, gross, or microscopic examination. The diagnosis should be suspected when a solid adnexal mass is associated with maternal hirsutism or virilization.

Uncomplicated pedunculated leiomyomas are usually hypoechoic compared with normal myometrium, but may have a complex appearance when there is necrosis or degeneration.

The presence of pain should suggest the possibility of heterotopic pregnancy, torsion or rupture of an ovarian neoplasm, or degeneration of a leiomyoma. (See "Ectopic pregnancy: Clinical manifestations and diagnosis", section on 'Heterotopic pregnancy' and "Ovarian and fallopian tube torsion" and "Evaluation and management of ruptured ovarian cyst" and "Uterine fibroids (leiomyomas): Epidemiology, clinical features, diagnosis, and natural history", section on 'Fibroid degeneration or torsion'.)

Malignant neoplasms — Epithelial ovarian tumors comprise approximately one-half of all ovarian malignancies in pregnant patients, germ cell ovarian malignancies make up approximately one-third, and stromal tumors and a variety of other tumor types (eg, sarcomas, metastatic tumors) account for the remainder (figure 1).

Epithelial ovarian tumors — Approximately 50 percent of epithelial ovarian tumors detected in pregnancy are of low malignant potential (formerly called "borderline"), and the other 50 percent are invasive. Epithelial ovarian tumors of low malignant potential diagnosed in pregnancy may exhibit atypical characteristics suggestive of invasive cancer such as nuclear enlargement, anisocytosis, and multifocal microinvasion. (See "Borderline ovarian tumors" and "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Clinical features and diagnosis".)

Germ cell tumors — Approximately three-fourths of malignant ovarian germ cell tumors in pregnancy are dysgerminomas; endodermal sinus tumors, immature teratomas, and mixed germ cell tumors comprise the remainder [15]. Most germ cell tumors are grossly limited to one adnexa, but lymphatic spread to pelvic or para-aortic nodes occurs, most commonly in dysgerminoma [16]. Dysgerminomas are bilateral in 10 to 15 percent of cases; other germ cell tumors are almost always unilateral. (See "Ovarian germ cell tumors: Pathology, epidemiology, clinical manifestations, and diagnosis".)

Sex cord-stromal tumors — Approximately half of all pregnancy-associated stromal tumors are granulosa cell tumors, one-third are Sertoli-Leydig cell tumors, and the remainder are unclassified stromal tumors [17]. Most of these tumors are limited to one ovary at the time of diagnosis. Prior to the routine use of prenatal ultrasound, approximately 20 percent of these lesions presented with intraperitoneal hemorrhage and/or hemorrhagic shock, but this has become less common with earlier diagnosis.

Between 10 and 15 percent of stromal tumors secrete androgens and produce virilization. Although estrogen secretion also occurs, symptoms of a hyperestrogenic state are masked by the already high estrogen concentration associated with pregnancy.

Pregnancy-related histologic changes in these tumors include a disorderly arrangement of cells, increased edema, and unusually large numbers of lutein or Leydig cells [17]. (See "Sex cord-stromal tumors of the ovary: Epidemiology, clinical features, and diagnosis in adults".)

DIAGNOSIS — Definitive diagnosis can only be made by resecting the ovarian neoplasm for pathologic examination. However, some benign ovarian masses, including follicular or corpus luteal cysts, endometriomas, and mature teratomas (dermoid), have characteristic sonographic features, and the diagnosis is reasonably certain without surgical exploration.

It is important that ovarian tissue is examined by a pathologist skilled in interpretation of histologic findings in the context of an ongoing pregnancy and that the pathologist is informed of the coexistent pregnancy. Pregnancy-related changes in the histologic appearance of tumors of low malignant potential can result in atypical characteristics suggestive of invasive cancer. In one series, 8 of 10 serous neoplasms diagnosed in pregnancy had microscopic and clinical features suggesting aggressive behavior; however, all of these features regressed postpartum in this small series, confirming that the neoplasms were of low malignant potential [18].

DIAGNOSTIC EVALUATION

Patient selection for surgery — The general consensus regarding management of adnexal masses in pregnancy is to surgically resect asymptomatic masses that are present after the first trimester and (1) are >10 cm in diameter or (2) are solid or contain solid and cystic areas or have papillary areas or septae [1,4,12,19-23]. The rationale for this approach is that these findings increase the likelihood of malignancy, and it is desirable to diagnose malignancy, if present, at an early stage. In addition, resection of large adnexal masses (benign or malignant) reduces the risk of complications such as adnexal torsion, rupture, or obstruction of labor [24]. Emergency surgery during pregnancy for management of a torsed or ruptured adnexal mass is uncommon (<5 percent of cases [1,25]) and can lead to preterm delivery [19,20,26].

Adnexal masses that do not have concerning features (eg, persistence into the second trimester, large size, or solid components) are likely to be physiologic cysts and can be managed expectantly [1,24,27-33], and often resolve during pregnancy. Expectant management is also appropriate for cysts with these features if the sonographer is reasonably certain that the neoplasm is a follicular or corpus luteal cyst, endometrioma, or mature teratoma. Surgical treatment of endometriomas depends upon whether the patient is symptomatic. Most mature teratomas are benign, but surgery may be indicated postpartum to prevent torsion (see "Ovarian germ cell tumors: Pathology, epidemiology, clinical manifestations, and diagnosis", section on 'Mature cystic teratomas'). For any ovarian mass, if the diagnosis is uncertain, further evaluation is required. Up to 10 percent of adnexal masses that persist during pregnancy are malignant [4,28,34]. A substantial portion of these are epithelial low malignant potential tumors or germ cell tumors, both tumors with a typically favorable prognosis. (See "Approach to the patient with an adnexal mass", section on 'Other high-risk premenopausal patients'.)

Timing — The optimal time for semi-elective surgery during pregnancy is after the first trimester for a number of reasons:

Almost all functional cysts will have resolved by this time.

Organogenesis is mostly complete, thus minimizing the risk of drug-induced teratogenesis.

The hormonal function of the corpus luteum has been replaced by the placenta, so reduction in progesterone secretion from oophorectomy or cystectomy does not result in loss of the pregnancy if not replaced.

Spontaneous pregnancy losses due to intrinsic fetal abnormalities are likely to have already occurred and will not be erroneously attributed to the surgery.

Postponing the surgery until after delivery may be performed in select cases [35].

Preoperative assessment — In most cases, the preoperative workup for a pregnant patient with a pelvic mass can be limited to ultrasound imaging [24]. If the ultrasound findings cannot distinguish between a possible pedunculated or degenerating leiomyoma and an ovarian neoplasm, we suggest obtaining magnetic resonance imaging (MRI). The more precise diagnosis afforded by MRI may be useful in opting for expectant management until delivery [36]. (See "Adnexal mass: Ultrasound categorization".)

A routine preoperative chest radiograph is unnecessary; however, if the history and physical examination suggest pulmonary disease, then a chest radiograph should be obtained with shielding of the abdomen/pelvis.

Secondary imaging — In most cases, ultrasound examination provides sufficient information to guide a decision for exploratory surgery versus conservative, expectant management, but occasionally, further radiologic evaluation is required. MRI has excellent resolution for soft tissue pathology and does not expose the patient (or fetus) to ionizing radiation. Therefore, MRI is particularly useful in characterizing a pedunculated leiomyoma, red degeneration of leiomyomas, endometriomas, decidualized endometriomas, and massive ovarian edema and distinguishing these lesions from ovarian cancer [36,37]. Gadolinium-based contrast material should generally be avoided in pregnancy because fetal safety has not been established. (See "Diagnostic imaging in pregnant and lactating patients", section on 'Use of iodinated contrast materials'.)

Computed tomography (CT) is avoided in pregnant patients if other imaging methods can provide the needed information [35]. The fetal ionizing radiation dose for a single CT through the pelvis is 0.035 Gy. Although fetal radiation exposure of less than 0.05 Gy has not been associated with an increased risk of abortion, congenital anomalies, growth restriction, or perinatal mortality, there remain concerns regarding a possible increase in the risk of developing childhood cancer [38,39]. In addition, the use of iodinated contrast agents with CT carries a risk of transient suppression of the fetal thyroid. (See "Diagnostic imaging in pregnant and lactating patients".)

Tumor markers in ovarian malignancy — Although serum tumor markers are routinely drawn preoperatively when planning a laparotomy for management of a pelvic mass in nonpregnant patients, we do not suggest this approach during pregnancy. Pregnancy-associated pelvic masses are infrequently malignant, and the interpretation of these tumor markers varies with gestational age and comorbid conditions. If a malignancy is proven, then appropriate tumor markers may be drawn in the immediate postoperative period.

Several of the tumor markers used to follow epithelial and nonepithelial ovarian cancers in nonpregnant patients (table 1) are difficult to interpret in pregnancy because oncofetal antigens (eg, alpha-fetoprotein [AFP], human chorionic gonadotropin [hCG], carcinoembryonic antigen [CEA], cancer antigen 125 [CA 125]) are involved in biological functions associated with fetal development, differentiation, and maturation. The levels are normally elevated during gestation and fluctuate with gestational age, or they may be abnormally elevated due to abnormal placentation or fetal abnormalities (eg, preeclampsia, Down syndrome, open neural tube defect) [13].

Serum CA 125 — Serum levels of CA 125 are elevated in most cases of epithelial ovarian cancer (EOC). CA 125 is also produced by normal tissues, including endometrium, and may be elevated during early gestation and immediately following delivery (table 2) [13]. However, CA 125 may be helpful as a tumor marker of EOC between 15 weeks of gestation and delivery, as serum values at this time are unlikely to be markedly elevated solely as a consequence of pregnancy. A CA 125 in the range of 1000 to 10,000 is likely (but not invariably) related to cancer, but values in the range of 75 to 150 could be either pregnancy-related or due to an ovarian cancer that does not demonstrate high expression of CA 125.

Alpha-fetoprotein — Maternal serum levels of AFP (MSAFP) normally rise during pregnancy; serum levels are routinely assayed as part of the screen for fetal neural tube defects and Down syndrome. High MSAFP levels are seen in some types of ovarian germ cell tumors (eg, endodermal sinus tumor, embryonal carcinoma, and mixed tumors). These levels are often >1000 ng/mL, especially with pure endodermal sinus (yolk sac) tumors, which can be associated with levels >10,000 ng/mL [40,41]. By comparison, MSAFP levels are typically <500 ng/mL in pregnancies complicated by neural tube defects. (See "Ovarian germ cell tumors: Pathology, epidemiology, clinical manifestations, and diagnosis".)

During pregnancy, AFP results are typically expressed as multiples of the median (MoM) for each gestational week because these values are easy to derive, more stable, and allow for inter-laboratory variation. MSAFP levels that are above 2.0 to 2.5 MoMs are considered abnormal. The AFP levels associated with ovarian cancer typically translate into much higher MoM values than seen with neural tube defects. In one case report, a MSAFP of 26,300 ng/mL translated into a MoM value of 24 [42]; in another, a level of 477.8 int. unit/mL (370 ng/mL) translated into a MoM of 12.5 [43]. Some authors suggest that a MSAFP level above 9 MoM should prompt concern for germ cell tumors of either gonadal or nongonadal origin in the absence of fetal abdominal wall defects or anencephaly [42]. (See "Neural tube defects: Overview of prenatal screening, evaluation, and pregnancy management" and "Maternal serum marker screening for Down syndrome: Levels and laboratory issues".)

Lactate dehydrogenase — Serum lactate dehydrogenase (LDH) is elevated in the serum of patients with ovarian dysgerminomas and is a reliable marker for diagnosis and follow-up of these tumors in pregnant patients [44]. LDH is not elevated in normal pregnancy, although elevations can occur in some pregnancy-related disorders such as preeclampsia and HELLP syndrome (Hemolysis, Elevated Liver function tests, Low Platelets) [45]. (See "Ovarian germ cell tumors: Pathology, epidemiology, clinical manifestations, and diagnosis", section on 'Dysgerminoma' and "Preeclampsia: Clinical features and diagnosis" and "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)".)

Inhibin A — Although serum inhibin A is a useful tumor marker for following the course of treatment for ovarian granulosa cell tumors in nonpregnant patients, inhibin A is made in the developing placenta, and serum levels are elevated in early gestation [46,47]. This limits the value of inhibin A as a tumor marker during pregnancy. Like AFP, inhibin A levels may be measured as a component of screening for Down syndrome. Inhibin A concentrations are, on average, twofold higher in pregnancies complicated by Down syndrome than in unaffected pregnancies. (See "Sex cord-stromal tumors of the ovary: Epidemiology, clinical features, and diagnosis in adults" and "Maternal serum marker screening for Down syndrome: Levels and laboratory issues".)

Human chorionic gonadotropin — The beta subunit of hCG is a useful marker for some germ cell neoplasms (particularly choriocarcinoma, (table 1)). However, it cannot be used as a tumor marker during pregnancy due to the large physiologic increase in this hormone. (See "Human chorionic gonadotropin: Biochemistry and measurement in pregnancy and disease".)

Human epididymis protein 4 (HE4) — Human epididymis protein 4 (HE4) is the product of the WFDC 2 (HE4) gene that is overexpressed in ovarian cancer. Assessment of the HE4 level is approved for monitoring patients with ovarian cancer for disease recurrence or progression, but not for screening. In a study of serum samples from 67 pregnant patients without ovarian cancer, median HE4 values were significantly lower in pregnant patients than in healthy, nonpregnant, premenopausal patients (30.5 versus 46.6 pmol/L) [48]. The 95th percentiles for HE4 in pregnant patients in the first, second, and third trimesters were 49.6, 35.1, and 50.2 pmol/L, respectively. Levels were measured using an enzyme immunometric assay (EIA) assay kit from Fujirebio Diagnostics Inc. In another series, higher concentrations of HE4 were detected in pregnant versus nonpregnant serum, but were not statistically significant. The authors concluded that HE4 serum biomarkers are unaffected by pregnancy [49], and therefore may be helpful in the evaluation of pelvic masses in pregnancy.

SURGERY — Issues related to preparation of the pregnant patient for nonobstetric surgery and management of anesthesia in pregnant patients are reviewed separately. (See "Anesthesia for nonobstetric surgery during pregnancy".)

Laparoscopy is an acceptable alternative to laparotomy for management of benign adnexal masses in pregnancy [50]. In a meta-analysis of four studies (one was a randomized trial) with a total of 240 patients evaluating laparoscopic versus open surgery for management of adnexal masses in the second trimester, laparoscopy was associated with better surgical outcomes but longer operative times. Of note, the laparoscopic group had smaller ovarian cysts.

If a malignancy is suspected, a laparotomy should be performed. A Pfannenstiel incision should be avoided, as it would not provide sufficient exposure. The vertical midline incision should be adequate to minimize the need to manipulate the gravid uterus while obtaining exposure to the adnexal mass.

Immediately after entry into the peritoneal cavity, peritoneal washings should be obtained for staging purposes in case the mass is malignant. The opposite adnexa should be carefully inspected and palpated for a contralateral adnexal mass. Contralateral ovarian biopsy is recommended if the ovary appears to be involved, but routine biopsy or wedge resection of a normal-appearing contralateral ovary is unwarranted.

The most common findings at surgery are persistent corpus luteal functional cysts, benign dermoid cysts, and serous or mucinous cystadenomas. If the preoperative imaging and intraoperative gross findings are both consistent with a benign diagnosis, it is reasonable to attempt a cystectomy rather than perform a salpingo-oophorectomy. If the mass is larger than 10 cm, it may not be technically feasible to perform an ovarian cystectomy. If the mass is solid, has surface excrescences, is associated with ascites, or has other features suggesting malignancy, then ipsilateral salpingo-oophorectomy is appropriate. The mass should be sent for frozen section and the pathologist informed of the concurrent pregnancy. Resection of the contralateral ovary should not be performed unless bilateral disease is identified; this decision must await the frozen section analysis. All suspicious lesions should be biopsied.

If the pathologist confirms a malignant tumor at frozen section, the surgeon should be prepared to complete an adequate surgical staging procedure, and a gynecologic oncologist should be consulted. The general principles of the staging procedure for a malignant ovarian tumor are described in the table (table 3) and in detail separately. Obviously, hysterectomy is not performed if preservation of the pregnancy is desired, and the surgeon must individualize each case, weighing the pros and cons of staging versus potential risk to the mother and fetus. In certain malignant germ cell tumors of the ovary (eg, endodermal sinus tumors), lymph node dissection may be omitted, as the patient will require chemotherapy based on the histopathology alone. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Surgical staging".)

Adequate surgical staging is of particular importance for stage I cancers (ie, those that are limited to the ovary (table 4)), as many, but not all, of these neoplasms are adequately treated with surgery alone. In such cases, the need for postoperative adjuvant chemotherapy is determined by the histologic tumor type. Surgical staging (eg, sampling of lymph nodes) is less critical in the setting of obvious advanced disease (eg, stage IIIB/C disease), as these tumors (with the exception of tumors of low malignant potential) will require chemotherapy. (See "Chemotherapy of ovarian cancer in pregnancy" and "Treatment of malignant germ cell tumors of the ovary" and "Sex cord-stromal tumors of the ovary: Epidemiology, clinical features, and diagnosis in adults".)

If a metastatic ovarian cancer is identified, cytoreduction should be attempted. The extent of surgical cytoreduction involves individual judgment, balancing the extent of surgery with the expected benefit. It is rare that removal of the gravid uterus is required for maximal cytoreductive surgery at the initial surgery because it is possible, if necessary, to return for secondary cytoreduction following chemotherapy and successful completion of the pregnancy. This management strategy is not thought to adversely impact survival, although as a general rule, survival is poor for patients who have late-stage disease.

Despite the importance of early surgical debulking to outcomes in ovarian cancer, the surgeon should keep in mind the sensitivity of these tumors to platinum-based chemotherapy when aggressive resection of metastatic disease is considered. With modern platinum-based adjuvant chemotherapy, approximately 70 percent of patients who present with advanced disease will respond to chemotherapy, even if they have residual disease remaining after cytoreductive surgery.

The hazard of overly aggressive surgery and delay in starting chemotherapy can be illustrated by a case report of a patient with a yolk sac tumor that was resected at 19 weeks of gestation [51]. Chemotherapy was delayed because of the pregnancy and at 32 weeks of gestation, tumor recurrence necessitated a cesarean-hysterectomy and bowel resection with colostomy. Three weeks later, the colostomy was taken down and another suprahepatic tumor mass was resected. The patient was then given bleomycin, etoposide, and cisplatin (BEP) for four cycles, but the course was complicated by a fecal fistula that developed at the colostomy site. (See "Chemotherapy of ovarian cancer in pregnancy".)

For patients with advanced-stage ovarian cancer diagnosed before delivery, hysterectomy and secondary cytoreductive surgery are reasonable postpartum to remove persistent disease. This surgery can be performed following vaginal birth or in conjunction with cesarean birth. This approach has been taken by a few investigators who reported managing advanced epithelial ovarian cancer (EOC) cases during pregnancy [52-55]. In four case reports, two patients had persistent disease involving the adnexa [52,53], two cases involved the bowel [53,54], and one case also involved the pelvic peritoneum, omentum, and appendix [53].

Management of corpus luteum — Removal of the corpus luteum should be avoided prior to eight weeks of gestation because the corpus luteum is primarily responsible for progesterone production and maintenance of the pregnancy at this time [56]. If the corpus luteum is removed prior to eight weeks, progesterone supplementation should be given as a 50 to 100 mg vaginal suppository every 8 to 12 hours or as a daily intramuscular injection of 1 mL (50 mg) progesterone in oil. After eight weeks, the ovary gradually shifts progesterone production to the placenta (called the luteal-placental shift) [57]. As of 10 weeks of gestation, the placenta is the primary provider of progesterone, so progesterone supplementation is no longer indicated. (See "Anesthesia for nonobstetric surgery during pregnancy".)

Adnexal mass at cesarean delivery — At cesarean birth, any adnexal mass that appears suspicious for malignancy should be removed and sent for frozen section. Complete surgical removal is preferred to aspiration and cytologic evaluation of cystic fluid, since malignancy could be missed with the latter. If the mass is an incidental finding at cesarean birth, the patient typically will not have an appropriate incision for surgical staging. In these cases, if frozen section indicates malignancy, salpingo-oophorectomy is performed and postpartum, the patient is referred to a gynecologic oncologist for counseling, staging, and possible hysterectomy within the next one to two weeks.

If an adnexal mass suspicious for malignancy is detected antepartum, the patient should be counseled and consented appropriately. Cesarean birth should be performed through a midline incision, and a gynecologic oncologist should be available, if required. After delivery of the infant and placenta and control of bleeding, the adnexal mass is resected and sent for frozen section. If positive for malignancy, full surgical staging can be performed. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Surgical staging".)

CHEMOTHERAPY — (See "Chemotherapy of ovarian cancer in pregnancy".)

PROGNOSIS — As with nonpregnant patients, the prognosis of pregnant patients with ovarian tumors depends on tumor histology, stage, and grade. The majority (approximately 75 percent) of invasive ovarian malignancies in pregnant patients are early-stage disease [58]. Due to the favorable mix of stage, grade, and histology, the five-year survival rate for ovarian tumors associated with pregnancy is between 72 and 91 percent [59,60]. The presence of ascites at diagnosis implies advanced disease and poor prognosis [59].

Data regarding mortality in pregnant patients are conflicting. In a nationwide cohort study conducted in Sweden from 1970 to 2018 including 5781 patients with ovarian and fallopian tube cancer, those with pregnancy-associated cancers (PAC; patients diagnosed with cancer during pregnancy or within the first year postpartum; 181 patients) compared with non-PACs had similar mortality rates; the median follow-up time was almost seven years [61]. By contrast, one cohort study found that postpartum lactating patients diagnosed with ovarian cancer had a poorer prognosis than patients diagnosed before or during pregnancy; however, the number of cases was small [62]. In a subsequent retrospective study including 764 premenopausal patients with ovarian cancer, those with cancers diagnosed during compared with remote from pregnancy had a greater risk of death (adjusted hazard ratio [aHR] 2.6, 95% CI 1.12-6.03) [60]; the risk of death was similar for those with cancers diagnosed postpartum compared with remote from pregnancy.

The decision to continue or terminate a pregnancy when ovarian cancer is diagnosed in the first trimester should be individualized and made by a fully informed patient in collaboration with the clinician. Early termination of pregnancy does not improve the outcome of ovarian cancer. In addition to the usual reasons for pregnancy termination, some factors that should be considered in patients with ovarian cancer include:

Whether the patient is willing to assume a possible risk of fetal toxicity or complications from ovarian cancer treatment during pregnancy.

The patient's prognosis and ability to care for the offspring.

The effect of ovarian cancer treatment on future fertility.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ovarian and fallopian tube disease".)

SUMMARY AND RECOMMENDATIONS

Prevalence – Approximately 0.05 to 2.4 percent of pregnancies are complicated by an adnexal mass, and approximately 1 to 6 percent of these masses are malignant. (See 'Prevalence' above.)

Presentation – Most pregnant patients with an adnexal mass are asymptomatic and the mass is discovered incidentally either on obstetric ultrasound examination or at cesarean birth. Symptoms of ovarian cancer include abdominal or back pain, constipation, abdominal swelling, and urinary symptoms, which are also almost universally present during normal pregnancies. (See 'Patient presentation' above.)

Tumor markers – An unexplained elevation in some maternal serum analytes (table 1), obtained during screening for neural tube defects or Down syndrome, can be a sign of an ovarian germ cell tumor. (See 'Patient presentation' above and 'Tumor markers in ovarian malignancy' above.)

Types of masses – Most adnexal masses identified in pregnant patients are benign simple cysts <5 cm in diameter and are functional ovarian cysts, either follicular or corpus luteum cysts, that occur as part of the normal physiological function of the ovary. Approximately 70 percent of all adnexal cystic masses detected in the first trimester spontaneously resolve by the early part of the second trimester. The majority of persistent adnexal masses ≥5 cm in diameter are dermoids. Up to 10 percent of adnexal masses that persist during pregnancy are malignant. (See 'Types of adnexal masses in pregnant patients' above.)

Diagnosis – Definitive diagnosis can only be made by resecting the ovarian neoplasm for pathologic examination. However, some benign ovarian masses, including follicular or corpus luteal cysts, endometriomas, and mature teratomas (dermoid), have characteristic sonographic features and the diagnosis is reasonably certain without surgical exploration. Pregnancy-associated ovarian tumors should be evaluated by a pathologist skilled in reading the pathologic findings in the context of the ongoing pregnancy, and the pathologist should be informed of the coexistent pregnancy. (See 'Diagnosis' above.)

Management

We suggest surgical resection rather than expectant management of asymptomatic masses present after the first trimester that are (1) >10 cm in diameter (Grade 2C) or (2) solid or containing solid and cystic areas or papillary areas or septae (Grade 2B). These findings increase the likelihood of malignancy, and it is desirable to diagnose malignancy, if present, at an early stage. In addition, resection of large adnexal masses reduces the risk of complications (eg, adnexal torsion, rupture, obstruction of labor). However, we suggest expectant management of asymptomatic corpus luteal cysts, endometriomas, and mature teratomas (dermoid) during pregnancy if the diagnosis is reasonably certain based on the sonographic characteristics (Grade 2C). (See 'Patient selection for surgery' above.)

Removal of the corpus luteum prior to eight weeks of gestation requires postoperative progesterone supplementation. (See 'Management of corpus luteum' above.)

Type of surgery

If the preoperative imaging and intraoperative gross findings are both consistent with a benign diagnosis, we suggest cystectomy rather than salpingo-oophorectomy (Grade 2C). If the mass is >10 cm, it may not be technically feasible to perform an ovarian cystectomy. If the mass is solid, has surface excrescences, is associated with ascites, or has other features suggesting malignancy, then ipsilateral salpingo-oophorectomy is appropriate. The mass should be sent for frozen section. Resection of the contralateral ovary should not be performed unless bilateral disease is identified. All suspicious lesions should be biopsied. (See 'Surgery' above.)

Adequate surgical staging is important for stage I cancers, as many of these neoplasms are adequately treated with surgery alone. Surgical staging (eg, sampling of lymph nodes) is less critical in advanced disease (eg, stage IIIB/C disease), as most of these tumors require chemotherapy. If a metastatic ovarian cancer is identified, the extent of surgical cytoreduction involves individual judgment, balancing the extent of surgery with the expected benefit. Before delivery, we leave as much of the reproductive tract in situ as possible, as patients with advanced-stage epithelial ovarian cancer can undergo completion of debulking of the reproductive organs following delivery. (See 'Surgery' above.)

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Topic 3201 Version 33.0

References

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