Ovarian cysts and cancer in pregnancy

Adnexal masses are diagnosed in 5% pregnancies and pose diagnostic and management challenges. Ultrasound and magnetic resonance imaging (MRI) are the mainstay as an evaluation procedure; surgery is warranted for persistent masses with a diameter of >5 cm and sonographic signs of possible malignancy. Optimal timing for a planned surgery is the second trimester and does not adversely affect neonatal outcome. Laparoscopy is safe in pregnancy. Management for ovarian cancer during pregnancy should be individualised and formulated by a multidisciplinary team in a specialised centre while also considering the patients’ wishes to preserve pregnancy. The following options can be considered: (i) induced abortion followed by standard management of ovarian cancer, (ii) pregnancy-preserving surgery followed by chemotherapy, planned delivery and secondary surgical completion or (iii) neoadjuvant chemotherapy followed by surgery during the postpartum period. Standard chemotherapy administered in non-pregnant population can only be used during the first trimester of pregnancy.

Highlights

  • Ovarian cancer in pregnancy should be managed by experienced and multidisciplinary team.

  • Obstetric outcome is not adversely affected by the management of ovarian cancer.

  • The best time for surgery is the second trimester of pregnancy.

  • Standard chemotherapy for ovarian cancer can be administered only during the first trimester of pregnancy.

Introduction

Ovarian masses in pregnancy, which can range from innocuous corpus luteal cysts to malignant ovarian tumours, pose a challenge from both a diagnostic and management point of view. The incidence of adnexal masses in pregnancy has been variably reported as 0.15–5.7%; clinically significant masses range from one in 25 to one in 8000 pregnancies . A higher trend in reporting is possibly explained by the increasing use of ultrasound (USS) as a routine antenatal evaluation and postponing childbearing to an older age.

Malignant adnexal masses during pregnancy range between 0.8% and 13% . The reported incidence of ovarian cancer (OC) in pregnancy varies from 1 in 15,000 to 1 in 32,000 and it is amongst the top five cancers diagnosed during pregnancy . With the increasing maternal age, it is expected that more women will be diagnosed with OC in pregnancy in the future, therefore management guidelines should be formulated with a regular update and review of recent literature .

Several articles have addressed the issues pertaining to the diagnosis of an adnexal mass, management algorithms specific to each trimester, use of laparoscopy and laparotomy during pregnancy while also considering the foetus. In this study, we intend to focus on the complexities of managing OC in pregnancy, especially when the role of primary cytoreduction to no macroscopic residual disease or extensive staging procedures is gaining momentum and increasingly debated within the gynaecological oncologist community.

Ovarian cysts in pregnancy

Dermoid cyst, cystadenoma, functional corpus luteal cysts and endometrioma are the most common causes for benign ovarian cysts in pregnancy . In addition, ovarian hyper-stimulation and polycystic ovaries should be kept in mind, especially with a history of infertility ( Tables 1–3 ).

Table 1
Incidence of ovarian cysts and ovarian cancer in pregnancy.
Author n Incidence of Ovarian cysts (%) Incidence of malignancy including tumours of low malignant potential (%)
Sherard 60 0.15 13
Balci 36 5.8
Türkçüoğlu 35 0.3 8.5
Bromley 131 0.8
Schmeler 63 0.05 7.9
Cohen-Herriou 71 0.35 4.2
Leiserowitz 9375 0.19 2.15
Chittacharoen 118 0.10 2.9
Table 2
Ovarian cysts in pregnancy.
Author Gestation age at diagnosis Gestation age at surgery Commonest histopathology
Sherard 12 20 Mature cystic teratoma (50%)
Balci 17 (5–36) 24 (6–41) Functional ovarian cyst (41.1%)
Türkçüoğlu Dermoid cyst (40%)
Bromley 12 2 nd trimester Dermoid cyst (30%)
Schmeler 12 Dermoid cyst (42%)
Cohen-Herriou Functional ovarian cyst (74.39%)
Hoover First trimester 12–27 weeks Dermoid (25%)
Table 3
Differential diagnoses of adnexal masses in pregnancy – adapted from RCOG Green Top Guidelines No. 62.
Benign ovarian Functional cysts Endometrioma Mature teratoma Serous cystadenoma Mucinous cystadenoma
Benign non-ovarian Distended bladder Para-tubal cyst Hydrosalpinx Pedunculated myoma. Peritoneal pseudocyst Pelvic kidney Urachal cyst Tubo-ovarian abscess Appendicular mass
Malignant primary Germ-cell tumour Epithelial malignancies Sex-cord stromal tumours
Malignant secondary Breast and gastrointestinal malignancies
Gestational Ectopic pregnancy IUP in bicornuate uterus.

Most adnexal masses are diagnosed incidentally in the first trimester during the routine dating scan, unless investigated earlier for infertility: 65–80% are asymptomatic, and almost three-fourth resolve spontaneously, with those persisting beyond 16–20 weeks indicating definitive pathology. Mature cystic teratoma and borderline ovarian tumour (BOT) are the most common histopathological diagnosis amongst persistent masses .

Ovarian cysts in pregnancy

Dermoid cyst, cystadenoma, functional corpus luteal cysts and endometrioma are the most common causes for benign ovarian cysts in pregnancy . In addition, ovarian hyper-stimulation and polycystic ovaries should be kept in mind, especially with a history of infertility ( Tables 1–3 ).

Table 1
Incidence of ovarian cysts and ovarian cancer in pregnancy.
Author n Incidence of Ovarian cysts (%) Incidence of malignancy including tumours of low malignant potential (%)
Sherard 60 0.15 13
Balci 36 5.8
Türkçüoğlu 35 0.3 8.5
Bromley 131 0.8
Schmeler 63 0.05 7.9
Cohen-Herriou 71 0.35 4.2
Leiserowitz 9375 0.19 2.15
Chittacharoen 118 0.10 2.9
Table 2
Ovarian cysts in pregnancy.
Author Gestation age at diagnosis Gestation age at surgery Commonest histopathology
Sherard 12 20 Mature cystic teratoma (50%)
Balci 17 (5–36) 24 (6–41) Functional ovarian cyst (41.1%)
Türkçüoğlu Dermoid cyst (40%)
Bromley 12 2 nd trimester Dermoid cyst (30%)
Schmeler 12 Dermoid cyst (42%)
Cohen-Herriou Functional ovarian cyst (74.39%)
Hoover First trimester 12–27 weeks Dermoid (25%)
Table 3
Differential diagnoses of adnexal masses in pregnancy – adapted from RCOG Green Top Guidelines No. 62.
Benign ovarian Functional cysts Endometrioma Mature teratoma Serous cystadenoma Mucinous cystadenoma
Benign non-ovarian Distended bladder Para-tubal cyst Hydrosalpinx Pedunculated myoma. Peritoneal pseudocyst Pelvic kidney Urachal cyst Tubo-ovarian abscess Appendicular mass
Malignant primary Germ-cell tumour Epithelial malignancies Sex-cord stromal tumours
Malignant secondary Breast and gastrointestinal malignancies
Gestational Ectopic pregnancy IUP in bicornuate uterus.

Most adnexal masses are diagnosed incidentally in the first trimester during the routine dating scan, unless investigated earlier for infertility: 65–80% are asymptomatic, and almost three-fourth resolve spontaneously, with those persisting beyond 16–20 weeks indicating definitive pathology. Mature cystic teratoma and borderline ovarian tumour (BOT) are the most common histopathological diagnosis amongst persistent masses .

Assessment of ovarian masses during pregnancy

Clinical assessment and imaging are the mainstay; histopathological diagnosis may be indicated only in selected cases. Tubo-ovarian abscess and ectopic pregnancy should be excluded as it is potentially life threatening. The goal of the diagnostic workup of an adnexal mass should be to differentiate between ovarian and non-ovarian causes, and if ovarian, to differentiate between benign and malignant masses .

Clinical assessment

A thorough physical examination after excluding a full bladder should evaluate signs of infection or neoplasm including assessment of cervical/supraclavicular/groin lymphadenopathy, breast examination, pleural effusion or ascites. Bimanual and rectovaginal examinations are useful for endometriosis; masses felt anterior to the uterus may suggest dermoid cysts. With the advent of better imaging modalities, routine per vaginal examination during pregnancy is being performed less frequently due to a generally poor sensitivity for detection of ovarian masses and the risk of introducing ascending infection. It may, however, help to rule out obstetric complications such as miscarriage, ectopic gestation and preterm labour and in resource poor settings, triaging prior to referral for transvaginal USS.

Radiological assessment

USS is considered the investigation of choice ; routine USS during pregnancy is usually done at 11–13 +6 weeks and then at 18–20 weeks of gestation. Up to 70% cysts identified during the first trimester resolve spontaneously by 18–20 weeks ( Table 4 ). Size and morphology are used to decide between intervention and surveillance as well as identifying which patients need an elective lower uterine caesarean section (LUCS) at term. The B and M rules for USS diagnosis of malignancy described by the International Ovarian Tumour Analysis (IOTA) group have 78% specificity and 87% sensitivity ( Tables 5 and 6 ) . Doppler indices change rapidly during pregnancy, hence is not consistently used and reported in pregnancy .

Table 4
Resolution of masses detected on USS in the first trimester with size.
Author N Incidence <5 cm simple >5 cm or Complex Disappearance
Bernhard 1999 432 2.6% 76% 24% 68.6%
Zanetta 2003 82 1.2% 50% 19.4% 58%
Condous 2004 182 5.4% 29.51% 71.1%
Table 5
IOTA ‘simple rules’ for categorization of adnexal mass – adapted from RCOG Green Top Guidelines No. 62.
B Rules M Rules
Unilocular cyst Irregular solid tumor
Presence of solid component, largest <7 mm Ascites
Acoustic shadowing At least four papillary structures
Smooth multilocular tumor with largest diameter <10 cm Irregular multilocular solid tumor with largest diameter ≥ 10 cm
No blood flow Very strong blood flow
Table 6
USS features and predicted resolution of ovarian masses.
Diagnosis USG Features Resolution
Simple cyst anechoic cyst without septa or vegetations 69%
Endometriosis or corpus luteum like hypoechoic content, either homogeneous or trabecular, no papillae 77%
Dermoid like combination of hyperechogenic and hypoechogenic content, shadows 0%
Complex benign septa, thick content but no papillae 57%
Borderline-like smooth capsule, presence of intracystic papillae, absence of gross solid parts 0
Suspicious solid parts, irregular capsule or border, ascites, irregular vascularization

Contrast-enhanced magnetic resonance imaging (MRI) has a sensitivity and specificity of 100% and 94%, respectively, in the diagnosis of malignancy and has negligible risks to the foetus; it may be a useful adjunct when USS is inconclusive/insufficient to guide management . Contrast enhancement may help to delineate solid components in a cystic mass and non-enhanced areas in a tarted mass. Gadolinum is teratogenic in animal studies and is classified as a category C drug by the Food and Drug Administration (FDA); more stable macrocyclic agents, that is, gadoteridol and gadobuterol may be considered. Left lateral decubitus positioning should be considered to avoid caval compression by the gravid uterus.

The American College of Radiology recommends MRI and USS for imaging during pregnancy . Use of computed tomography (CT) scans is disfavoured; ionising radiation or the contrast crossing the placental barrier may pose a risk in terms of neurological and cardiological damage to the foetus and the risk of developing childhood cancers. If the MRI is not available, the use of CT scan after weighing the potential risks to the foetus with maternal benefit may be justified. Hurwitz et al. recommended the following to reduce radiation exposure to the foetus ; (i) lowering the current tube, (ii) limiting the coverage in z axis (iii) increasing the helical pitch (iv) reducing gantry cycle time. A single multidetector-row computed tomography (MDCT) protocol exposes the foetus to 3.5 cGy; the safe limit of neurological damage is <10 cGy.

Role of tumour markers

CA 125 is an antigenic determinant expressed with epithelial ovarian tumours, but it is physiologically elevated during pregnancy; increased CA 125 is seen at 30–40 days peaking at 35–60 days of gestation and a fall by the end of the first trimester . In addition, majority of pregnant patients present with stage I disease, and only 50% of early-stage tumours have a CA 125 above 30 IU . Tumour markers that are typically elevated in germ-cell tumours including alphafetoprotein (AFP), lactate dehydrogenase (LDH) and human chorionic gonadotropin (hCG) are also altered during pregnancy, limiting their clinical utility. Baseline values for prognostication may be obtained in the puerperal period after 4–6 weeks.

Complications

Persisting masses have the potential to cause complications in 10–30% of pregnancies including acute sequelae like torsion, haemorrhage, rupture and obstruction of labour, which cause potential adverse perinatal outcome . Persistence of abdominal pain and hemodynamic instability may indicate emergency laparotomy irrespective of the gestational age of the patient. Rarer presentations include diagnosis during caesarean section or hormonally active tumours like granulosa, Sertoli–Leidig cell and sex cord–stromal tumours, which may present with features like abdominal pain, swelling, shock, virilisation and vaginal bleeding .

Torsion

Pregnancy increases the risk of torsion (19.9 % vs. 9%) due to displacement of the ovaries from the pelvis during uterine enlargement . Majority of torsion events occur between 15 and 17 weeks of gestation. Additional risk factors include in vitro fertilisation and tumour sizes of 6–8 cm.

Rupture

Rupture of functional cyst is common; however, it rarely causes symptoms severe enough for intervention or spontaneous rupture during pregnancy. Iatrogenic rupture after fine-needle aspiration or intraoperative cyst rupture due to tumour handling should be minimized to avoid chemical peritonitis and accidental peritoneal seedling of an early-stage ovarian malignancy.

Obstruction of labour

Similar to obstructing fibroids, large adnexal masses may predispose to labour dystocia (2–17%) if located near the lower uterine segment and below the presenting part .

Management

There is no consensus in the literature regarding surgical or conservative management of benign adnexal masses during pregnancy . Generally, ovarian cystectomy or a salpingo-oophorectomy (BSO) is performed for a benign pathology. There is a theoretical risk of pregnancy loss with oophorectomy before 9–11 weeks of gestation; surgery at 16–20 weeks may ensure (i) spontaneous resolution of masses, (ii) better uterine visualisation and exclusion of congenital anomalies in foetus and (iii) reduced risk of preterm labour. Surgery should not be delayed beyond 23 weeks in view of poorer outcomes with the delayed treatment of the malignancy. Improvements in imaging assessment have led to a reduction in the rate of negative surgeries performed to identify an ovarian malignancy from 14:1 to 2.5:1 . For lesions suspicious of malignancy on preoperative imaging, a frozen section is helpful. Poorer outcomes are associated with emergency surgeries as compared with elective ones . Aggarwal and Kehoe elucidate certain principles of managing an adnexal mass in their evidence-based review ( Fig. 1 ) and summarized as follows :

  • 1.

    A conservative approach is justified for asymptomatic masses detected incidentally on first trimester USS.

  • 2.

    If symptomatic or USS shows features of malignancy, surgery should be undertaken. MRI is advised if malignancy cannot be confidently excluded. If surgery is planned, it should be performed in the second trimester.

  • 3.

    If USS shows no features of malignancy, repeat the USS at 18–20 weeks at the time of the congenital anomaly scan. A mass detected in the third trimester with no features of malignancy should be left undisturbed until the time of CS or 6 weeks’ postpartum.

Nov 6, 2017 | Posted by in OBSTETRICS | Comments Off on Ovarian cysts and cancer in pregnancy

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