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Ovarian Cysts

by

Thomas Ind

Consultant Gynaecological Surgeon

St George's & Royal Marsden Hospitals

Introduction
Ovarian cysts can be functional (part of normal physiology), endometriotic, or neoplastic. Neoplastic ovarian cysts can be benign, borderline, or malignant. The management of each of these is different. However, only when a specimen is analysed in the pathology laboratory can we know for sure what the diagnosis is. A clinician has to utilise his/her clinical acumen and the results of investigations to help determine management and make a clinical diagnosis. 

Functional cysts
Follicular and Corpus Luteal cysts are simple cysts on ultrasound. They occur in reproductive life and can be confused with neoplastic lesions. The management is usually by observation alone. Sometimes it is necessary to aspirate them or perform an ovarian cystectomy. These cysts can also be treated by suppressing ovarian activity with the contraceptive pill.

Endometriotic cysts
Endometriotic cysts are sometimes called chocolate cysts. They are cysts of endometriosis that occur on the ovary and contain chocolate appearing material formed from old blood.

They occur in reproductive age and classically present with pain which is worse just before and during menstruation. Painful Mittlesmertz (ovulation pain) can also occur along with other symptoms of endometriosis such as dyspareunia (painful sex). On ultrasound scan the cysts have no loculations or solid elements but contain a characteristic echogenicity caused by the disorganised blood within the cyst cavity.

Treatment is normally surgical although they do respond to some medical treatments for endometriosis such as the contraceptive pill, high dose progesterones, and GnRH analogues. There are a number of surgical treatments for endometriotic cysts including both laparoscopic and open approaches. Cysts can be aspirated, drained, LASERed, or stripped. Evidence from the literature supports stripping of the endometrioma from the ovary as the most effective method of treating these cysts. This is normally done laparoscopically. These cysts usually occur in conjunction with endometriosis in other sites of the pelvis. When this occurs, these other sites can be treated at laparoscopy by LASER or diathermy and medical treatment can also be utilised to treat symptoms.

Ovarian Neoplasms
Ovarian neoplasms can arise from the ovarian epithelium, sex cord/stromal tissue, or germ cells. Cysts can be malignant or benign. However, some epithelial tumors are classified as borderline as histologically they show characteristics of malignant tumors but are not invasive. Borderline tumors can recur and be of a high stage. Seven percent dedifferentiate into invasive cancers if left untreated. A classification of ovarian cysts is listed below;

- SEROUS TUMORS
These are the most common epithelial tumors and account for about 50% of malignant and 20% of benign cysts. 20% of benign cysts are bilateral and classically they are unilocular and contain a straw coloured fluid. Serous tumors may be borderline. Borderline tumors with serous papillary components are the worst type of borderline tumors with the highest predisposition to dedifferentiate.

- ENDOMETRIOID TUMORS
These are the second most common malignant tumors and are rarely benign. They closely mimic endometrial cancers histologically and can co-exist with endometrial cancers.

- MUCINOUS TUMORS
These form about 20% of ovarian cysts and are benign 90% of the time. When benign they are usually unilateral but 20% of malignant mucinous tumors occur on both sides. Mucinous tumors can be borderline. Benign tumors are classically multiloculated and contain a mucinous fluid. In some cases, mucinous tumors can exist with pseudomyxoma peritoneii which is a condition characterised by a gelatinous material throughout the peritoneal cavity. Pseudomyxoma peritoneii is more classically associated with mucinous tumors of the appendix and it is for this reason that the appendix is removed when an ovarian tumor is known to be mucinous.

- CLEAR CELL
These are always malignant and carry a poor prognosis.

- BRENNER
These tumors contain urothelial-like cells. They are normally benign but can be malignant. They often occur in association with serous tumors.

- GRANULOSA CELL TUMORS
These account for about 5% of ovarian malignancies. About 70% secrete sex hormones of which the most common is oestradiol. It is for this reason that granulosa cell tumors may present as precocious puberty if they occur in children. The prognosis for granulosa cell tumors is good although they can recur many years after successful initial treatment.

- THECOMA/FIBROMA TUMORS
Thecomas arise from theca-lutein cells. They are usually benign as are fibromas. An ovarian fibroma can co-exist with a pleural effusion which resolves when the fibroma is removed. This is called Meig's Syndrome.

- SERTOLI/LEYDIG TUMORS
These account for less than 1% of ovarian tumors and are usually benign. They occur in younger women (teens and early 20s) and may produce androgens.

- TERATOMA
These can be benign mature teratoma (Dermoid Cysts) or immature teratomas. They contain elements from all three embryonic germ lines (mesoderm, ectoderm, and endoderm). Mature teratomas account for a quarter of all benign ovarian cysts (50% in women under 20) and can contain any element such as sebum, hair, teeth, thyroid tissue and even brain tissue. It is possible to have hyperthyroidism due to thyroid tissue ina dermoid and this is called struma ovarii. Immature teratomas can occur but are rare.

- DYSGERMINOMA
Dysgerminomas are the most common malignant germ cell tumor (50%) although they represent only a few percent of all ovarian cancers. They classically have a macroscopic appearance of a 'cut potatoe' and normally occur in women in their 20s.

- YOLK SAC & ENDODERMAL SINUS TUMORS
These germ cells tumors are rare and usually occur in women under 20. Classically they produce AFP and have normal hCG levels.

- CHORIOCARCINOMA
Unlike choriocarcinomas that arise from gestational trophoblastic disease, ovarian choriocarcinomas carry a poor prognosis. They usually occur in women under 20 and secrete hCG.

- METASTATIC TUMORS
Metastatic tumors of the ovary are quite common and can arise from the GI tract, breast, and uterus. When they arise from the GI tract they are commonly called Krukenberg tumors.

Differential diagnosis
As can be seen from the above, the differential diagnosis is large. A cyst can be functional, endometriotic, benign, borderline, or malignant. However, a pelvic mass may also be a metastatic tumor or a lesion arising from another pelvic organ such as the rectum or Fallopian tube. Diverticular abscess are commonly misdiagnosed as being ovarian cysts. A clinician has to be very careful about the possible differential diagnosis. For example, a woman with gastrointestinal symptoms must have these investigated to exclude a gastrointestinal cancer or diverticular disease. If a cyst exists in a woman under 40, AFP and hCG measurements should be done to rule out germ cell tumors.

Ruptured cyst
Functional cysts can become very large and rupture. This normally presents with a sudden onset of very severe right or left sided pain. This pain can be severe enough to require admission to casualty and intravenous analgesia usage. Ultrasound scan is often normal as the cyst has ruptured although there is often fluid seen in the Pouch of Douglas. The pain is normally self limiting and goes after about 6 hours. It is often followed by a heavy menstrual blood loss.

Haemorrhagic cyst
Acute and severe pelvic pain can also be caused by haemorrhage into a cyst. This pain is normally of sudden onset and very severe. If often persists for longer than a ruptured cyst.

Torted ovarian cyst
Sometimes a cysts can twist on a pedicle consisting of the infundibulo-pelvic ligament and Fallopian tube. This cuts off the blood supply to the ovary and causes it to become gangrenous. This causes an acute onset of severe pelvic pain and emergency surgery is often required.

History
A medical history is very important in the diagnosis of an ovarian cyst. Symptoms such as pain may help in ascertaining the presence of an endometriotic cysts. It is important to discuss the onset of pain, duration and relationship to the menstrual cycle. Age is an important factor as a young woman is less likely to have an ovarian malignancy. Associated symptoms such as bowel or urinary symptoms are also important to enquire about. A family history of breast or ovarian cancer may also be an indicator in the history.

Examination
As well as a general examination it is important to examine the abdomen to see if the pelvic mass is palpable and also to determine if there is any associated liver enlargement or ascites. A pelvic examination is required to determine the masses size and mobility and a pelvo-rectal examination is required to ascertain if there is any rectal tethering as there sometimes is with ovarian malignany.

Investigations
General bloods: It is important to look at general signs of ill health. Anaemia can occur in a haemorrhagic cyst, a high white cell count and ESR can occur in infected lesions such as a pyosalpinx. Urea and electrolytes are usually performed and can be abnormal with advanced ovarian cancer. Liver function tests are performed for the same reason. Thyroid function can be altered in some Dermoid cysts and should also be measured.
 
CA125: A CA125 is elevated in most ovarian cancer. It can also be elevated with some benign cysts.

Germ cell markers: Women under the age of 40 should have their AFP and hCG measured to rule out the rare cases of choriocarcinoma and yolk sac tumors.

Other tumor markers: A CA19.9 (pancreas), CA15.3 (breast), and CEA (bowel) should be measured to help rule out other cancers. A CA19.9 is often mildly elevated with mucinous cancers.

Ultrasound: A pelvic ultrasound (usually performed transvaginally) is one of the best methods of assessing a pelvic mass. It can help distinguish between simple and complex masses. Furthermore, doppler studies can be performed. Features that make a cyst at high risk of ovarian cancer include;

Bilaterality
Solid element and papillary projections
Multiple loculations
Ascites
Abnormal dopplers

CT scan: CT is not as good as ultrasound in assessing pelvic masses. However, it is good as detecting extra-pelvic disease that is present in ovarian cancer.

MRI scan: MRI scanning is good at characterising pelvic masses. It is probably as good as ultrasound but is much more expensive. It has the advantage of being able to assess the pelvic lymphnodes and adjacent structures more efficiently.

Immunoscintigraphy: Immunoscintigraphy is where radioactive labelled monocloncal antibodies are used to help identify ovarian cancer cells. A gamma camera is used to help identify spread.

Risk of Malignancy Index: The RMI is a statistical equation used to calculate the risk of cyst being cancerous. There are a number of different RMIs but the most commonly used one is;

    MP x CA125 x USS

MP = menopausal status (1 = pre, 2 = post)

CA125 = CA125 value

USS = Number of suspicious ultrasound features (0 = none, 1 = one, 3 = more than one).

Management based on Risk of Malignancy Index (RMI)
Modern management is based heavily on the risk of malignancy index (RMI). If the RMI is less than 25 then the risk of ovarian malignancy is the same as the population risk. Therefore treatment is dependant on symptoms. If the RMI is over 200 then there is a strong risk of cancer. Therefore, treatment is usually as if a patient has ovarian cancer (see handout on ovarian cancer). Between 25 and 200 a more conservative management is acceptable. This is either by short term observation or excision of the cyst or ovary alone by laparoscopic techniques.

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