CHAPTER 44 Benign tumours of the ovary
Introduction
Ovarian cysts are common, frequently asymptomatic and often resolve spontaneously. They are the fourth most prevalent gynaecological cause of hospital admission. By 65 years of age, 4% of all women in England and Wales will have been admitted to hospital for this reason. Ovarian cysts are found either during the course of investigation of abdominal pain or as a result of imaging for other reasons. It is important to distinguish between ovarian cysts that will require assessment and management and those that will resolve spontaneously. In addition, reliable prediction of their benign or malignant nature would be beneficial in order to arrange appropriate referral and management, as per Improving Outcome Guidance (NHS Executive 1999).
Physiological Ovarian Cysts
As pelvic ultrasound, particularly transvaginal scanning, is now used more frequently, physiological cysts are detected more often. The corpus luteum may persist and continue to secrete progesterone beyond its natural lifespan, and thus cause some menstrual irregularity, or haemorrhage may occur into the cyst at or just after ovulation. Most good radiologists will recognize the features of a follicle, corpus luteum or haemorrhagic cyst and will report these as such. Most simple cysts will resolve spontaneously over a period of 6 months (Zanetta et al 1996, Saasaki et al 1999). Occasionally, they can persist for longer or grow in size to become a clinical problem. Physiological cysts should simply be regarded as large versions of the cysts which form in the ovary during the normal cycle.
Failure of development of the lead follicle results in anovulation and is a classical finding in polycystic ovary syndrome (PCOS). PCOS is predominantly an endocrine abnormality, and polycystic ovaries do not cause abdominal pain (see Chapter 18, Polycystic ovary syndrome, for more information).
Clinical Presentation of Symptomatic Ovarian Cysts
Benign ovarian cysts present as follows:
Pain
Acute-onset pain
For a woman to present with acute-onset abdominal pain in the presence of an ovarian cyst suggests a cyst accident such as torsion, rupture or haemorrhage. Torsion usually gives rise to an acute-onset sharp, constant pain caused by ischaemia of the cyst. Areas may subsequently become infarcted if there is delay in treatment, and pyrexia may develop. Haemorrhage may occur into the cyst and cause pain as the capsule is stretched. Intraperitoneal bleeding mimicking ectopic pregnancy may result from rupture of the cyst, which is most often a ruptured, bleeding corpus luteum.
If the patient is haemodynamically unstable at the time of presentation, resuscitation and stabilization are priorities. At a minimum, a full blood count, cross-match and urinary human chorionic gonadotrophin (hCG) should be performed. If the urinary hCG is positive, a serum quantitative hCG would help in the diagnostic process. If it is possible to obtain emergency ultrasound imaging, this may be beneficial but surgery should not be delayed whilst waiting for investigations which would not necessarily affect the management.
Chronic pain
Pelvic inflammatory disease may give rise to a mass of adherent bowel, hydrosalpinx or pyosalpinx. In such circumstances, the pain will be gradual in onset rather than acute. It is often difficult to distinguish between a hydrosalpinx and an ovarian mass on ultrasound; if there is a diagnostic dilemma, laparoscopy should be considered.
Abdominal swelling, bloating and pressure effects
Patients seldom note abdominal swelling until the tumour is very large. A benign mucinous cyst may occasionally fill the entire abdominal cavity. Bloating is a common symptom which can be associated with ovarian tumours but most often is not. Gastrointestinal or urinary symptoms may result from pressure effects. In extreme cases, oedema of the legs, varicose veins and haemorrhoids may result. Sometimes, uterine prolapse is the presenting complaint in a woman with an ovarian cyst.
An attempt to assess symptoms qualitatively and quantitatively in order to distinguish women who may have an ovarian cyst from those unlikely to have a cyst suggests that recent-onset, severe and persistent symptoms should warrant further investigation (Bankhead et al 2008).
Hormonal effects
Occasionally, the patient will complain of menstrual disturbances but this may be coincidence rather than due to the tumour. Rarely, ovarian tumours present with oestrogen effects such as precocious puberty, menorrhagia, glandular hyperplasia, breast enlargement and postmenopausal bleeding. Secretion of androgens may cause hirsutism and acne initially, progressing to frank virilism with deepening of the voice and clitoral hypertrophy. Very rarely indeed, thyrotoxicosis may occur. Some of these tumours are malignant, but are mentioned here because of their ability to produce hormones in some cases. The hormonal effects and histology are discussed later.
Differential Diagnosis
The differential diagnosis of benign ovarian tumours is broad, reflecting the wide range of presenting symptoms.
Investigation
The investigations required will depend upon the circumstances of the presentation. The patient presenting with acute symptoms will usually require emergency surgery, whereas the asymptomatic patient or the woman with chronic problems may benefit from more detailed preliminary assessment.
Gynaecological history
Details of the presenting symptoms and a full gynaecological history should be obtained, with particular reference to the date of the last menstrual period, the regularity of the menstrual cycle, any previous pregnancies, contraception, medication and family history (particularly of ovarian or breast cancer).
General history and examination
Indigestion or dysphagia combined with profound weight loss might indicate a primary gastric cancer metastasizing to the pelvis. Similarly, a history of altered bowel habit or rectal bleeding should be sought as evidence of diverticulitis or large bowel carcinoma. Ovarian carcinoma may also present with these features.
If the patient has presented as an emergency, evidence of hypovolaemia should be sought. Hypotension is a relatively late sign of blood loss, as the blood pressure will be maintained for some time by peripheral and central venous vasoconstriction. When decompensation of this mechanism occurs, it often does so very rapidly. It is vital to recognize the early signs (i.e. tachycardia and cold peripheries). In these circumstances, it is not appropriate to delay surgery pending further investigations, and laparotomy is the correct course of action.
If a cyst is found, the chest should be examined for signs of a pleural effusion. Peripheral oedema can indicate both pressure symptoms and hypoproteinaemia. It is also important to rule out other sites of tumours that are known to metastasize to the ovary, such as the breasts; thus, a full clinical examination is indicated.
Abdominal examination
The abdomen should be inspected for signs of distension by fluid or by the tumour itself. Dilated veins may be seen on the lower abdomen. Gentle palpation will reveal areas of tenderness and peritonism. The best way of detecting a mass that arises from the pelvis is to palpate gently with the left hand, starting in the upper abdomen and working caudally. This is the reverse of the process taught to every medical student for feeling the liver edge. Use of the right hand alone is the most common reason for failing to detect pelvic–abdominal masses.
Shifting dullness is probably the easiest way of demonstrating ascites, but it remains a very insensitive technique. If present, examination of the chest is required to determine if a pleural effusion is also present. It is always worth listening for bowel sounds in any patient with an acute abdomen. Their complete absence in the presence of peritonism is an ominous sign.
Bimanual examination
This is an essential component of the assessment because, even in expert hands, ultrasound examination is not infallible. By palpating the mass between both the vaginal and abdominal hands, its mobility, texture and consistency, the presence of nodules in the pouch of Douglas and the degree of tenderness can be determined. While it is impossible to make a firm diagnosis with bimanual examination, a hard, irregular, fixed mass is likely to be invasive.
Investigations
As a minimum, urine should be tested for the presence of infection and pregnancy. Blood should be obtained for a full blood count, blood grouping and cross-match if the patient is haemodynamically unstable. If the clinical signs suggest the possibility of upper gastrointestinal pathology, liver function tests and serum amylase should be performed.
Serum tumour markers
CA125 is well established in the investigation of ovarian cysts. It is a tumour marker for peritoneal disease/irritation, and whilst not specific for ovarian cancer, a level above 30 u/ml is abnormal. Benign conditions that increase the level of CA125 are endometriosis and pelvic inflammatory disease. In an acute cyst accident, it may also be raised; however, levels above 250 u/ml are almost always associated with malignant disease. The level of CA125 is increased in 80% of ovarian cancers. Other tumour markers may be useful in certain circumstances. If the tumour has features suggestive of a teratoma (dermoid), alpha-fetoprotein and hCG help to determine its malignant potential. Carcinoembryonic antigen, C15.3 and C19.9 are indicated when there is a possibility of pathology other than primary ovarian. Occasionally, the ovary may contain a rare tumour called a ‘granulosa cell tumour’; in this case, serum inhibin levels are useful in tracking the course of disease.
Ultrasound
The techniques of transabdominal and transvaginal ultrasound are discussed in detail in Chapter 6. Ultrasound is the single most important investigation and can demonstrate the presence of an ovarian mass with 81% sensitivity and 75% specificity. Most ovarian masses are cystic, whilst the presence of solid areas makes a malignancy more likely. Reporting of an ultrasound finding of an ovarian cyst has been standardized in order to allow for the allocation of a scoring system to assist in the preoperative assessment of the risk of any ovarian cyst being malignant. The ultrasound is awarded a U score of 0 if no cyst is present, 1 if only one characteristic is found, and 3 if two or more characteristics are found:
Computed tomography (CT) scanning has no significant advantages over ultrasound in cyst assessment, but can be useful in the presence of obvious extrapelvic disease to assess tumour bulk prior to chemotherapy. Magnetic resonance imaging (MRI) has a marginal advantage over CT in determining if a cyst is more likely to be benign or malignant, but both have no benefit over good transvaginal ultrasound and should not be used routinely. Initial studies using colour flow Doppler were promising but, once again, its use has not been proven to improve cyst assessment.
Risk of malignancy index
There is good evidence that primary surgery undertaken by a gynaecological oncologist improves survival in ovarian cancer by allowing for adequate staging and optimal debulking. It is not practical for all cysts to be managed by gynaecological oncologists; thus, in order to triage cysts for the appropriate surgeon, the Royal College of Obstetricians and Gynaecologists (RCOG) recommend use of the risk of malignancy index (RMI). In order to calculate the RMI, the menopausal status is also taken into account, with premenopausal being awarded a score of 1 and postmenopausal being awarded a score of 3. This simple formula is used:
A score below 25 can be managed by any gynaecologist, a score of 25–250 should be managed by a cancer unit lead, and a score above 250 should be referred to a cancer centre. This assessment allows for 70% of ovarian cancers to be managed in a cancer centre. The specificity is 90%. The cysts most likely to result in confusion regarding their benign or malignant nature are endometriomas. The clinical history and examination may better inform the clinician but, as a general principle, a significantly raised CA125 (>300 u/ml) is almost always associated with malignant disease.
The Scottish Collegiate also uses an RMI scoring system but gives different weightings to the ultrasound findings and menopausal status. If there are two or more abnormal ultrasound features, they award a U score of 4, whilst a postmenopausal status also has a score of 4. In addition, referral to a cancer centre is recommended when the RMI score is above 200. These adaptations increase the sensitivity of the RMI for prediction of malignant disease from 70% to 80%, and increase the specificity from 89% to 92%. Many centres in the UK also apply this RMI.
Ultrasound-guided diagnostic ovarian cyst aspiration
This investigation has been introduced gradually into gynaecological practice without the benefit of appropriate trials to indicate its potential efficacy. Unfortunately, this technique has a false-negative rate of up to 71% and a false-positive rate of 2% for the cytological diagnosis of malignancy (Diernaes et al 1987
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