Ovarian cancer during pregnancy.

Among the benign entities encountered in pregnant patients, these are the most frequently encountered entities: Cystadenomas account for up to 50% of benign ovarian neoplasms in the general population. Up to 20% of cystadenomas are bilateral [ 4 ]. Serous cystadenomas are the most common subtype and may resemble simple cysts larger than typical functional cysts in US, while demonstrating high T2 and low T1 signal intensity in MRI [ 4 ]. Meanwhile, mucinous cystadenomas are usually multilocular cysts containing fluid of different viscosity; as such, they demonstrate varying echogenicity on US or signal intensity on T2-weighted MRI [ 4 ]. Serous/mucinous cystadenofibromas usually present as cystic masses, either unilocular or multilocular, with a solid component characterized by very low T2 signal intensity and without a restricted diffusion [ 19 ] ( Figure 1 ). Fibromas belong to the group of sex cord-stromal tumors. On US, fibromas typically appear as solid hypoechoic masses, although cystic spaces may appear due to degeneration. On MRI, fibromas are characterized by low signal intensity on T2-weighted imaging, DWI, and apparent diffusion coefficient (ADC) maps, a phenomenon known as the T2 blackout effect, similar to leiomyomas [ 4 ]. Dermoid cysts are usually distinctive in US, but the diagnostic finding on MRI, if performed, is the presence of macroscopic fat ( Figure 2 ). Dermoid cysts may undergo torsion [ 4 ].

US is the first-line modality for imaging adnexal masses during pregnancy; its routine use in prenatal imaging has contributed to the increased number of asymptomatic ovarian masses detected over the years [ 14 ]. It In addition, it cost-effective, widely available, and safe to use during pregnancy [ 1 , 5 , 10 ]. Both transabdominal or transvaginal US may be performed depending on the stage of pregnancy; however, as the pregnancy progresses, the uterus may obscure pelvic organs, reducing both the sensitivity and specificity of US [ 1 , 5 , 10 ]. During pregnancy, Doppler evaluation can also be challenging and less reliable, with an estimated false positive rate of 49% due to the augmented flow speed and reduced vascular resistance typical of pregnancy [ 6 ]. Although there have been no reports of documented adverse fetal effects from diagnostic ultrasound procedures, including Doppler imaging, it is essential to minimize fetal exposure risk with all modalities. There is a theoretical risk of fetal temperature elevation with ultrasound. This risk is lowest with B-mode and higher with color Doppler and spectral Doppler. Since ultrasound machines are configured differently for different indications, those configured for obstetrics do not produce the higher temperatures delivered by machines using nonobstetric transducers and settings. Users should be prudent with their use of ultrasound, but it does not pose a risk to the fetus or pregnancy when configured and used appropriately [ 15 ]. MRI is the second-line modality for imaging adnexal masses and is performed when lesions are too large to evaluate or are indeterminate on US. In an evaluation of 31 pregnant patients, MRI demonstrated an accuracy of greater than 88% with excellent sensitivity (100%) and specificity (78%−85%) [ 1 ]. Regarding the safety of MRI during pregnancy, there are two main concerns. The first is that during the first trimester, MRI may result in harm to the fetus due to the heating of sensitive tissues by the radiofrequency fields and exposure to a loud environment [ 16 ]. The second is that there may be risks associated with the exposure to gadolinium-based contrast agents, which are category C drugs that have been associated with increased skeletal malformations in the offspring of exposed animals [ 5 , 6 ]. A large study conducted in Canada evaluated 1,424,105 deliveries with a rate of 3.97 MRI examinations per 1,000 pregnancies [ 16 ]. The authors reported that exposure to MRI during the first trimester was not associated with an increased risk of harm to the fetus or the child during early childhood. However, the authors reported that the use of gadolinium contrast at any time during the pregnancy was associated with a risk of a wide-ranging set of rheumatological, inflammatory, or infiltrative skin conditions, as well as a risk of stillbirth or neonatal death. In line with these findings, ACOG states that the use of gadolinium contrast should be limited and may only be used in pregnant women if it significantly improves diagnostic performance and is expected to improve fetal or maternal outcomes [ 17 ]. Of note, the use of diffusion-weighted imaging (DWI) can reduce the need for gadolinium contrast and is particularly helpful for detecting peritoneal implants and nodal metastases [ 1 ]. Computed tomography (CT) has a limited role during pregnancy due to the potential risk of radiation, even though most radiation doses for a CT examination will be under the 100 mGy threshold for significant risk of fetal harm [ 18 ]. If available, an MRI examination should be considered in place of a CT examination, as the former is a safer modality during pregnancy [ 17 , 18 ]. While fluorodeoxyglucose (FDG) PET/CT may be useful to evaluate cancer in pregnancy, it is generally not widely available or even recommended [ 17 , 18 ]; MRI using the DWI technique is equally effective and safer for detecting nodal and distant metastasis as FDG PET/CT [ 18 ]. If FDG PET is necessary, a smaller administered dose and a longer imaging time are recommended. Additionally, increased oral hydration and frequent voiding or bladder catheterization should be considered to reduce fetal radiation exposure [ 18 ].

As previously mentioned, the frequency of malignant lesions during pregnancy is very low, less than 5% [ 1 , 4 , 6 ]. Malignant germ cell tumors are the most common type of malignancy encountered in pregnant patients, and among them, the most common subtypes are dysgerminoma (38%) and yolk sac tumors (30%). Less frequently encountered in pregnant patients are sex cord-stromal tumors such as granulosa cell tumors (22%), thecoma (18.6%), and Sertoli-Leydig cell tumors (8.5%) [ 24 ]. The other neoplasm commonly diagnosed during pregnancy is the borderline ovarian tumor , and of note, one-third of borderline ovarian tumors are diagnosed in women less than 40 years of age. Finally, epithelial ovarian cancer is exceedingly rare [ 9 ]. Most malignant germ cell tumors are rapidly growing and unilateral; however, in 10% of cases, dysgerminoma can be bilateral. Furthermore, most cases are diagnosed at an early stage. The two most commonly elevated tumor markers due to the presence of malignant germ cell tumors are alpha-fetoprotein, which can also be elevated in case of a fetal neural tube defect, and lactate dehydrogenase, which usually remains stable during the pregnancy [ 9 ]. The literature is scarce and mostly limited to case reports regarding the imaging features of dysgerminoma in pregnant patients; to date, their imaging appearance is reportedly similar to that in non-pregnant patients [ 25 – 27 ]. Dysgerminomas appear as solid masses with smoothly lobulated contours, that are divided into lobules by fibrovascular septa. On Doppler US, they are richly vascularized. On MRI, they typically have a low signal on T1-weighted imaging and are isointense to slightly hyperintense on T2-weighted imaging. The septa can be hyperintense on T2-weighted imaging when edematous changes are present [ 25 – 27 ] ( Figure 10 ). Similarly, the literature is mostly limited to case reports regarding the imaging features of yolk sac tumors in pregnant patients, and to date, their imaging appearance is also reportedly similar to that in non-pregnant patients. Yolk sac tumors usually appear as solid and cystic masses with a smooth contour and possible hemorrhage (hyperintense on T1-weighted imaging). On Doppler US, they are richly vascularized [ 28 – 30 ]. Usually, sex cord-stromal tumors behave similarly in pregnant and non-pregnant patients, presenting at an early stage and having a slow and indolent course (10). The most frequent subtype is the granulosa cell ovarian tumor . Tumor markers specific to sex cord-stromal tumors are inhibin and especially isoform B. The literature on sex cord-stromal tumors is scarce and mostly limited to case reports and case series [ 28 – 30 ]. To date, their imaging appearance is reportedly similar to that in non-pregnant patients. They tend to be polymorphous in morphology, have restricted diffusion, and could have an intraparenchymal hemorrhage, especially in the juvenile subtype [ 28 – 30 ] ( Figure 11 ). Regarding the clinical-pathological characteristics of borderline ovarian tumors in pregnant patients, the two largest clinical reviews found that these tumors tend to have a higher incidence of aggressive features, such as micropapillary patterns in serous borderline ovarian tumors and intra-epithelial carcinoma in mucinous borderline ovarian tumors [ 31 , 32 ]. The largest review, which was a retrospective multicenter study of 40 patients, found frequent incomplete initial staging [ 31 ]. The other review evaluated 10 cases of borderline ovarian tumors and found that aggressive tumors appear to regress at the termination of the pregnancy [ 32 ]. The two most frequent histologic subtypes, serous and mucinous borderline ovarian tumors, tend to have a typical presentation. Serous ovarian borderline tumors tend to present as cystic masses with papillary projections, which can have increased vascularity within the vegetation’s pedicle. Conversely, mucinous ovarian borderline tumors tend to be multicystic masses with an internal septa [ 33 ]. During pregnancy, and concerning the above-mentioned pathological findings, they can show greater complexity, with thickened walls or septa and internal solid portions rather than papillary projections [ 33 ] ( Figure 12 and 13 ). Similar to their appearance in non-pregnant patients, serous and mucinous cystadenocarcinomas in pregnant patients tend to have irregular solid nodules and thickened and irregular septa or present as solid and cystic masses. Furthermore, associated ascites, peritoneal implants, or abdominopelvic adenopathy suggest malignancy [ 4 ]. Finally, metastatic disease involving the ovaries is exceedingly rare in pregnant patients, and the most common primary tumors would be breast, colorectal, and gastric. They are usually solid bilateral masses, hypoechoic on US, and showing low-to-high signal intensity on T2-weighted imaging depending on the primary tumor type [ 4 ] ( Figure 14 ). A summary of the above-described imaging findings is highlighted in Table 1 .

Radiologists should be familiar with uncommon adnexal masses during pregnancy that can mimic malignancies, as well as with other non-ovarian processes that can mimic an ovarian process [ 4 ]. The first consideration should be to distinguish between adnexal and non-adnexal masses. In this regard, several imaging signs are helpful to determine the relationship of the mass with the ovary [ 4 , 18 ]. The “beak” sign is defined as sharp angles between the ovary and a mass, with the mass deforming the edges of the ovary into a beak shape. The beak sign suggests that the mass is of ovarian origin. In contrast, the “bridging vessel” sign and “claw” sign suggest that the mass originates from the uterus. The bridging vessel sign corresponds to vessels extending between the uterus and the mass, as seen with pedunculated uterine leiomyomas. The claw sign corresponds to uterine tissue draping over the mass and is also typically seen with uterine leiomyomas [ 4 , 18 ]. Para-ovarian cysts are ubiquitous and located in the mesosalpinx between the fallopian tube and ovary. On US, they appear as thin-walled anechoic structures; meanwhile, on MRI, they are hyperintense on T2-weighted imaging and hypointense on T1-weighted imaging [ 4 ]. Hydrosalpinx is the dilatation of the fallopian tube by fluid. It appears as a tubular anechoic cystic structure with incomplete septa on US and MRI. Fluctuations in size are possible [ 4 ]. Leiomyomas are ubiquitous and may mimic an ovarian mass if they are large, subserosal, and pedunculated. On US, they appear as hypoechoic solid masses with posterior acoustic shadowing. On MRI, non-degenerated leiomyomas appear as well-defined masses, with low signal intensity on T2-weighted imaging and low signal intensity on high- b -value DWI and ADC maps [ 4 ]. Notably, the MRI appearance of leiomyomas can vary owing to several types of degeneration or histologic variants, with cellular leiomyoma being the most common ( Figure 3 ). During pregnancy, leiomyomas may undergo spontaneous hemorrhagic infarction, known as “red degeneration” or as apoplectic leiomyoma in the last WHO classification. Also, it may undergo growth, or torsion, and can present with acute pain [ 4 ]. Ectopic pregnancies happen when a fertilized egg is implanted and grows outside the main cavity of the uterus, most often in the fallopian tube, although cervical or cornual ectopic pregnancy may also occur. The ectopic gestational sac appears as a cystic sac-like structure frequently associated with surrounding acute hematoma and shows low signal intensity on T2-weighted imaging and high signal intensity on T1-weighted imaging. Patients may present with acute pain and bleeding from ectopic pregnancy. During US, a patient may guide the radiologist to the ectopic pregnancy by pointing to where the pain is. Although infrequent, an ectopic pregnancy can present as heterotopic and coexist with an orthotopic pregnancy, and the former present as an “adnexal mass” during a regular obstetric ultrasound [ 4 , 20 ]. Hemorrhagic cysts present with a variable appearance on US, including internal heterogeneity, layering clots, and non-vascular septa. On MRI, they appear as cystic lesions with intrinsic high signal intensity on T1-weighted imaging, which does not have to be homogenous and is usually in a “layering” pattern without a solid component and does not suppress with fat saturation ( Figure 4 ) [ 4 ]. Endometriomas typically have homogeneous high signal intensity on T1-weighted imaging and variably reduced signal intensity on T2-weighted imaging, i.e., “T2 shading.” Identifying fibrotic changes within the pelvis in keeping with deep endometriosis may aid in diagnosing endometrioma [ 4 ]. Solid components within an endometrioma can be due to malignant transformation; however, they are rare (less than 1% of women with endometriosis) and may mimic a borderline serous tumor [ 21 ]. When seen during pregnancy, endometriomas may reflect ectopic decidualization, i.e., the ectopic occurrence of endometrial changes that form the vascular decidual lining of the uterus ( Figure 5 ) [ 1 , 4 ]. Helpful signs that suggest that a solid nodule represents decidualization, also seen as pseudo-papillary projections, are the vascular lobulated nodules within the wall of the endometrioma on US; and on MRI, the nodules present with the same signal intensity and texture as the decidualized endometrium, i.e., high signal intensity on T2-weighted imaging ( Figure 6 ) [ 1 , 4 ]. Imaging follow-up to document the resolution of ectopic decidualization after pregnancy is warranted [ 1 , 4 , 21 ]. Theca lutein cysts result from overstimulation of the ovaries by endogenous or exogenous gonadotropins, usually in the setting of assisted fertility, gestational trophoblastic disease, or multiple gestations. On both US and MRI, the ovaries are enlarged and demonstrate multiple thin-walled cysts [ 1 , 4 ]. Hyperreactio-luteinalis occurs in the third trimester of pregnancy in patients who have an increased sensitivity to circulating hCG, such as patients with hyperandrogenism due to polycystic ovarian syndrome. Patients may be asymptomatic or present with abdominal pain and distention, abnormal liver function tests, respiratory difficulties, and virilization. Similar to theca lutein cysts, on both US and MRI, the ovaries are enlarged and have multiple peripheral cysts. Spontaneous regression of the cysts is seen after delivery. Moreover, the cysts can appear as large multi-cystic ovarian masses resembling mucinous borderline ovarian tumors [ 1 , 4 ]. Tubo-ovarian abscesses should be suspected in patients with fever, elevated white blood cell count, pelvic pain, and vaginal discharge. On US, masses that are not identifiable as ovaries and that are associated with increased pain from direct probe pressure are highly suspicious for tubo-ovarian abscesses. On MRI, tubo-ovarian abscesses appear as thick-walled, fluid-filled masses in the adnexal region that are hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging, and moderate inflammatory changes can be seen on fat-saturated T2-weighted imaging [ 1 , 4 ]. Massive ovarian edemas are characterized by marked enlargement of one ovary (rarely both) due to diffuse stromal edema resulting in peripherally displaced follicles. Massive ovarian edemas may be secondary to subacute or chronic torsion without frank infarction. On MRI, the ovary is enlarged and is hyperintense on T2-weighted imaging [ 1 , 4 ] ( Figure 7 ). Pregnant patients are at increased risk of ovarian torsion. On US, ovarian torsions present as enlarged ovaries with a ground glass parenchymal appearance and peripheral repartition of the follicles. A twisted vascular pedicle known as the “whirlpool sign” on US is highly specific for ovarian torsion. On MRI, ovarian torsions appear as enlarged ovaries with high T2 signal intensity of the stroma and peripherally displaced follicles (5) ( Figure 8 ) [ 1 , 4 , 20 ]. It is essential to highlight that besides the expected presentation of ovarian stimulation syndrome, i.e., multiple cysts/follicles and some of them hemorrhagic, there is a possibility of a co-occurring incidental ovarian neoplasm, especially a borderline ovarian tumor. Therefore, when evaluating a patient who is undergoing fertility treatment, special consideration should be taken to assess the wall of the cysts/follicles for the presence of papillary projections or any other solid component that can suggest the diagnosis of a co-occurring ovarian neoplasm [ 22 , 23 ] ( Figure 9 ).

MRI is the modality of choice when US findings are inconclusive/indeterminate concerning adnexal masses. MRI is safe to perform during pregnancy, but gadolinium contrast should be avoided. Most adnexal masses in pregnant patients are benign in origin, such as functional cysts and mature cystic teratomas. Most cases of adnexal masses are also asymptomatic, but complications such as torsion can occur if a mass is present and it acts as a torsion point. Pregnancy changes can generate decidualization of endometrioma or increase the complexity of borderline ovarian tumors, mimicking malignancy. A few adnexal masses are malignant in origin, with imaging features similar to those in non-pregnant patients.

Of note, guidelines from national and international societies on the evaluation and management of adnexal masses in pregnancy are lacking. The American College of Obstetrics and Gynecology (ACOG) provides only a level C recommendation (i.e., a recommendation based primarily on consensus and expert opinion) for expectant management, given the low risk of malignancy or acute complications associated with adnexal masses [ 9 ]. Additionally, there is a lack of agreement in the literature, leading to an ongoing debate between surveillance and surgical management of adnexal masses during pregnancy [ 1 ]. Several authors have proposed indications for the removal of adnexal masses during pregnancy, including acute abdomen, size > 10 cm due to increased risk of complications, rapid growth (≥ 3.5 cm per week), and morphologic features that are suspicious for malignancy [ 10 – 13 ]. Notably, up to 71% of apparently benign ovarian masses will become smaller or disappear without any intervention, even those exhibiting more complex features [ 11 – 13 ]. Additionally, only 2%–5% of persistent adnexal masses are found to be malignant [ 11 – 13 ]. In case surgical management is decided, the second trimester (between weeks 15 and 20) would be the optimal time due to the lower risk of spontaneous abortion and avoidance of anesthetic agents during organogenesis, among others. The presurgical evaluation with imaging helps decide which approach to offer to patients. For example, with a presumptive diagnosis of dysgerminoma, granulosa cell tumor, or borderline ovarian tumor, a unilateral adnexectomy with preservation of the contralateral adnexa and gravis uterus may be offered. On the contrary, if epithelial ovarian cancer is suspected primary debulking surgery or neoadjuvant chemotherapy may be offered depending on a case basis [ 9 ]. In addition, while multiple systems have been developed to evaluate ovarian masses in non-pregnant women, including the International Ovarian Tumor Analysis (IOTA) system and the American College of Radiology’s Ovarian-Adnexal Imaging-Reporting-Data System (O-RADS), they have not been well evaluated in pregnant women [ 1 , 10 ]. Features of malignancy according to both these systems include the presence of solid components, increased wall thickness, multiloculated large tumors, internal septa greater than 2–3 mm, the presence of papillary projections, increased vascularity, and ascites [ 1 , 10 ].

In recent decades, the routine use of ultrasonography (US) during pregnancy has led to an increased number of diagnosed asymptomatic adnexal masses [ 1 , 2 ]. Yet, adnexal masses remain a relatively rare entity, occurring at a rate of one in 76 to 2,328 pregnancies [ 3 ]. Clinical management of adnexal masses is challenging; multidisciplinary team discussion should focus on weighing the risk of the tumor spreading if expectant management is pursued, against the risk of miscarriage, premature delivery, or potential fetal side effects if surgery is pursued [ 1 , 2 ]. In pregnant patients, transabdominal or transvaginal US with Doppler evaluation is the modality of choice for evaluating adnexal masses [ 4 , 5 ]. Magnetic resonance imaging (MRI) is the modality of choice to problem solve when US findings are indeterminate (20%) [ 1 , 4 , 6 ]. MRI is also beneficial for characterizing larger masses, evaluating their relationship to adjacent structures, and assessing the peritoneum and lymph nodes [ 7 ]. It is also important to note that CA-125 levels are typically elevated during the first trimester of pregnancy [ 8 ]. Most adnexal masses found during pregnancy are benign in origin. Specifically, up to 30% of these masses are functional cysts, either corpus luteum or follicular cysts, which usually regress spontaneously, and 24%–40% are benign tumors such as a mature cystic teratoma. Indeed, only fewer than 5% are malignant in origin [ 1 , 4 , 6 ]. Of note, although most cases of an adnexal mass are asymptomatic, complications can occur, including torsion (10%), rupture (2%), hemorrhage, and labor obstruction [ 1 , 4 , 6 ]. This review aims to familiarize the radiologist with the imaging of adnexal lesions during pregnancy, in particular, so that the radiologist can identify ovarian cancer. Specifically, the review will detail the most common benign and malignant adnexal masses in pregnancy, mimickers, and their corresponding imaging findings on US and MRI.