Abstract
Benign ovarian cysts are a common gynaecological presentation. Up to 10% of women will have surgery for an ovarian cyst in their lifetime. When an adnexal mass is diagnosed, the differential diagnosis is wide and up to 10% may be non-ovarian in origin. The goal of management is to determine the underlying pathology and to risk stratify patients to guide further management. Transvaginal ultrasound scanning remains the imaging modality of choice and the use of simple rules as well as benign and malignant features should form the basis for diagnosis, with serum markers used as an adjunct. Cross-sectional imaging with other modalities including magnetic resonance imaging are useful in the management of indeterminate masses. Most ovarian cysts are benign in nature and most functional and simple cysts are likely to resolve spontaneously without intervention. This review will demonstrate four clinical scenarios with different underlying pathology and their management.
Introduction
Ovarian cysts are a common gynaecological presentation, leading to surgery in up to 10% of women, making it the fourth most common gynaecological cause for hospital admission in the UK. Most premenopausal cysts are diagnosed incidentally, and therefore asymptomatic and the vast majority of presentations are benign – the overall incidence of a malignant ovarian cyst in the premenopausal woman is approximately 1–3 in 1000 cases, increasing with age.
Clinical features and assessment
When symptoms are present, they most commonly include lower abdominal and pelvic pain, increased urinary frequency and abdominal distension. In women with endometriomas and associated endometriosis their symptoms may include dysmenorrhoea, dyspareunia and dyschezia. A thorough history should include previous gynaecological and surgical history as well as risk factors for ovarian cancer, including a family history of ovarian and breast cancer. In particular a family history of BRCA 1 and 2 gene carriers and those with Lynch syndrome should be referred for additional counselling and discussion of risk reduction.
Clinical assessment should include abdominal and vaginal examination and examination for local lymphadenopathy. Assessment for tenderness, mobility, nodularity and the presence of ascites is important in risk stratification and pre-operative planning.
Investigations
The main objective in the management of ovarian cysts in premenopausal women is to classify the ovarian mass and to risk stratify for malignancy, balancing the risks and benefits of conservative and surgical options. Table 1 shows the range of differential diagnoses of adnexal masses; it is important to note that 10% of suspected ovarian masses are eventually found to be non-ovarian in origin. Transvaginal ultrasound scan remains the most cost-effective way to assess the morphology of adnexal masses and to determine the underlying pathology while blood tests for tumour markers are of some value when used in conjunction with ultrasound findings. Of note however is that these methods for risk stratification are not designed for, nor well validated in the premenopausal population where the incidence of malignancy is low.
| Benign adnexal masses of ovarian origin | Benign masses of non-ovarian origin | Malignant masses of ovarian origin |
|---|---|---|
| Functional ovarian cysts Endometriomas Sex cord stromal tumours: Fibroma Thecoma Sertoli cell tumour Leydig cell tumour Germ cell tumour Mature cystic teratoma Epithelial Serous cyst adenoma Mucinous cystadenoma Brenners tumour | Paratubal cyst Hydrosalpinges Tubo-ovarian abscess Peritoneal inclusion cysts | Epithelial carcinoma Serous cyst adenocarcinoma Mucinous cystadenocarcinoma Endometrioid carcinoma Clear cell carcinoma Borderline tumours Germ cell tumour Malignant teratoma Dysgerminoma Endodermal sinus tumour Sex-cord tumour Granulosa cell tumour Sertoli-Leydig cell tumour |
IOTA methods: easy descriptors and simple rules
The International Ovarian Tumour Analysis (IOTA) group developed a standardized approach based on ultrasound features of ovarian cysts/tumours, using ‘Easy Descriptors’ and ‘Simple Rules’. This approach is widely used in clinical practice. ‘Easy Descriptors’ are easily recognisable features on ultrasound scan used to predict the underlying diagnosis of an ovarian mass. The descriptors and associated diagnosis are shown in Table 2 and these enable a diagnosis to be made in approximately 40–50% of cases by pattern recognition.
| Easy descriptor | Predicted histology |
|---|---|
| Unilocular tumour with ground glass echogenicity in premenopausal women | Endometrioma |
| Unilocular tumour with mixed echogenicity and acoustic shadows in premenopausal women | Mature teratoma/dermoid cyst |
| Unilocular anechoic tumour with regular walls and maximum diameter <100 mm | Simple cyst/mucinous cystadenoma |
| Remaining unilocular cyst with regular walls | |
| Tumour with ascites and at least moderate colour Doppler blood flow in post-menopausal women | Malignancy |
| Age >50 years and CA125>100 U/ml | Malignancy |
Simple rules are based on a set of five ultrasound features consistent with benign tumours (B features) and five features consistent with malignant tumours (M-features) (see Table 3 ). Ovarian cysts may be classified as benign if only B-features are observed and malignant if any M-features are observed. This can be used to classify cysts in 80% of cases with a reported sensitivity of 91–96% and specificity of 68–93%. If no features are seen or if conflicting features are present then the ovarian tumour would be classified as indeterminate.
| Benign features (B-rules) | Malignant features (M-rules) |
|---|---|
| Unilocular cyst Presence of solid components where the largest component <7 mm Presence of acoustic shadowing Smooth multilocular tumour with largest diameter <100 mm No blood flow | Irregular solid tumour Ascites Four or more papillary structures Irregular multilocular solid tumour with largest diameter >100 mm Very strong blood flow |
The IOTA group have developed several different prediction models to improve diagnostic accuracy. These models are based on logistic regression analysis. These include LR1 which uses 12 different variables, LR2 which uses six different variables and Simple Rules risk model, which incorporates the Simple rules. Another model, the ADNEX (Assessment of Different Neoplasias in the Adnexa) model can also incorporate serum CA125 results in the risk prediction. It can also subclassify malignancies by stage. The main benefit of using these models, is the ability to provide a more individualized estimated risk of malignancy, incorporating variables such as ultrasound scan features, age, type of centre i.e. oncology centre or other centre. However, these models require the use of a computer or online calculator.
Further strategies for the characterization of indeterminate masses include the use of cross-sectional imaging including MRI scans. PET-CT or whole body diffusion MRI scans are also considered if metastatic tumours are suspected.
Blood tests including Lactate dehydrogenase (LDH), Alpha-fetoprotein (AFP) and serum Human chorionic gonadotrophin (HCG) are recommended in women under the age of 40 with a complex ovarian mass as a serum marker for germ cell tumours. Although CA125 is widely used as a biomarker for epithelial ovarian cancer it is of limited value in premenopausal women because it is raised in a number of benign conditions such as endometriosis, adenomyosis, fibroids and pelvic infection.
Although the Risk of Malignancy Index (RMI) is commonly used to determine the optimal place of surgery, it is of limited use in premenopausal women due to the number of benign diagnoses associated with raised CA-125 levels. Serum CA-125 (CA-125), menopausal status of the patient (M) and the ultrasound score (U) of the ovarian tumour is calculated (see Box 1 ) and a cut off RMI Score of 200 is used to predict ovarian malignancy. A RMI score of 200 or more has a sensitivity of 75% and specificity of 87% to diagnose malignancy.
RMI = U × M × CA-125
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Ultrasound score: 1 point for each of the following characteristics: Multilocular cysts, solid areas, metastases, ascites and bilateral lesions U = 0 (for ultrasound score of 0), U = 1 (for ultrasound score of 1), U = 3 (for ultrasound score of 2–5)
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Menopausal status is score as 1 = premenopausal, 3 = post-menopausal
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CA-125 as measured in IU/ml
A recent meta-analysis by Kaijser et al. examined 19 different prediction models, and reported that Simple Rules and LR2 with a risk cut-off of 10%, performed better than all the other models, including RMI, highlighting the benefits of using risk prediction models in characterizing adnexal masses.
Management
The management of benign ovarian cysts in premenopausal women will depend on the presence of symptoms, size of the lesion, fertility desires and the underlying pathology. Simple cysts measuring <3 cm should not be reported as they are likely functional and lead to unnecessary anxiety for women while those that measure between 3 and 5 cm do not require further follow-up. Simple cysts measuring >5 cm should be followed up by interval ultrasound scan and if persistent or larger than 7 cm, surgical removal would be considered. Other types of benign ovarian cysts and their management will be discussed in the sections below. Regarding surgical approach of ovarian cysts predicted to be benign in nature, laparoscopic surgery is associated with lower morbidity, shorter recovery and is preferred to laparotomy in patients without contraindications.
Case 1: mucinous cystadenoma in pregnancy
A 28-year-old patient attended the ultrasound department for her booking scan at 12 weeks gestation. The scan showed a singleton intrauterine pregnancy with fetal heart action seen, as well as a 6 cm simple cyst on the right ovary. This was an incidental finding and the patient was asymptomatic. She was managed conservatively initially but the patient presented at 16 weeks gestation with severe abdominal pain. An ultrasound scan showed the cyst had increased in size measuring 10 cm in diameter. Appearance was of an anechoic unilocular cyst, with a smooth outline and no septations. A laparoscopy was performed showing a 10 cm right ovarian cyst without signs of torsion. A cystectomy was performed and the histology confirmed a diagnosis of a mucinous cystadenoma.
Learning points
Adnexal masses are commonly identified during pregnancy, with a prevalence of up to 9%. Around three quarters of these are benign simple cysts measuring <5 cm and will resolve spontaneously or can be managed expectantly. The risk of ovarian malignancy in pregnancy is low with an estimated incidence of 1 in 15,000 to 32,000 pregnancies and the majority are borderline tumours of low malignant potential.
Greyscale ultrasound scan remains the main imagining modality in pregnancy, however there are limitations including displacement of the adnexa by the gravid uterus. Furthermore, use of common risk stratification models such as the IOTA simple rules discussed above have not been validated in pregnant women. In addition, the physiological and hormonal changes in pregnancy may alter the morphology and Doppler flow of benign cysts such as endometriomas, to mimic malignant features. When the ovarian mass is indeterminate or too large to be adequately assessed by ultrasound scan, Magnetic resonance imaging (MRI) is generally used as a second line imaging technique. However, the use of Gadolinium based contrast during pregnancy is controversial as it has been found to be teratogenic in animal studies. In addition, fetal movements will reduce MRI image quality. Serum markers such as CA-125 is of limited value in pregnancy as it is raised in 35% of normal pregnancies especially in the first trimester and epithelial carcinomas make up a lower proportion of malignancies in pregnancy. Other tumour markers such as inhibin B, LDH, Cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) are normal during pregnancy and may be useful as a serum cancer marker.
When managed conservatively, 70% of simple cysts are found to resolve spontaneously in pregnancy. Surgery is therefore generally reserved for pregnant women who present acutely with complications such as torsion and haemorrhage, where there are significant symptoms of pain, in cases where large cysts (eg. >10 cm) may lead to labour dystocia and in those where malignancy is suspected.
The main concern with surgery in pregnancy is the risk of miscarriage and premature delivery. Although there is sparse evidence to determine the optimal time for elective surgery in pregnancy the consensus is that surgery between 14 and 20 weeks gestation appears to be favoured. The reasons include:
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Organogenesis is complete, reducing the risk of teratogenesis.
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Placental function has replaced the corpus luteum and ovarian surgery would not compromise progesterone production.
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The risk of miscarriage is low compared to the first trimester.
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Functional cysts are likely to have resolved spontaneously by this gestation.
Although laparoscopic surgery is associated lower morbidity and shorter recovery in the non-pregnant population there are specific challenges in pregnancy. Some of these challenges and their proposed mitigating strategies are listed in Table 4 .
