Ovarian Cysts Workup

An ultrasonographic examination of the pelvis should be obtained if a patient is thought to have a pelvic mass on clinical examination. Always be vigilant about patients with an increased risk of ovarian cancer and arrange appropriate evaluation.  Complex ovarian masses should be assumed to be a cancer until proven otherwise, particularly in a patient who is post-menopausal or has a prior history of breast cancer or a family history of breast/ovarian cancer.

If a patient has large fibroids, it is possible to miss concomitant ovarian pathology clinically and on ultrasonographic examination.

Because of the routine use of ultrasonography, ovarian cysts are commonly diagnosed in pregnancy. ^[6] Cysts should be evaluated in pregnant patients in the same way that they are in nonpregnant patients, with ultrasonographic examinations; however, note that cancer antigen 125 (CA-125) testing is not reliable, particularly during early pregnancy. Magnetic resonance imaging (MRI) should be used rather than computed tomography (CT) scanning, but ultrasound is usually sufficient.

Histologic findings

The definitive diagnosis of all ovarian cysts is made based on histologic analysis. Each cyst type has characteristic findings.

Culdocentesis

Using needle aspiration to obtain fluid for cytologic examination provides inaccurate cytologic results, and needle aspiration is an inappropriate method for cyst drainage in most cases. In fact, because of its associated complications (bowel perforation, abscess rupture, trauma to a pelvic kidney), culdocentesis is now largely of historical interest. Its use has generally been replaced by ultrasonography. ^{[30, 31, 32]}

Diagnostic laparoscopy

Performing diagnostic laparoscopy may sometimes be necessary to inspect a suggestive adnexal cystic mass. Laparoscopy offers the advantage of decreased morbidity, improved postoperative recovery, and decreased cost compared with laparotomy.

No laboratory tests are diagnostic for ovarian cysts. However, the following laboratory tests can aid in the differential diagnosis and in the diagnosis of cyst-related complications:

• Urinary pregnancy test - Should always be performed in all women of childbearing age with abdominal pain or similar complaints

• Complete blood count (CBC) – Should focus on hematocrit and hemoglobin levels to evaluate for anemia caused by acute bleeding; the white blood cell (WBC) count may be elevated not only in complications of ovarian cyst, especially torsion, but also in infectious, pathologic abdominal conditions, such as appendicitis

• Urinalysis - Should be obtained to rule out other possible causes of abdominal or pelvic pain, such as urinary tract infections and kidney stone

• Endocervical swabs - Should be obtained to assess for chlamydia and gonorrhea if pelvic inflammatory disease is among the differential diagnoses

Cancer antigen 125

Keep in mind the possibility of cancer when managing an ovarian cyst. ^[33] Cancer antigen 125 (CA125) is a protein expressed on the cell membrane of normal ovarian tissue and ovarian carcinomas. A serum level of less than 35U/mL is considered normal, although in some laboratories, the upper limit of normal may be lower than this.

While CA125 values are elevated in 85% of patients with epithelial ovarian carcinomas overall, the value is elevated in only 50% of patients with stage I cancers confined to the ovary. ^[34] CA125 levels are also elevated in patients with some benign conditions or other malignancies and in 6% of healthy patients.

Moreover, CA125 should not be drawn in pregnant patients with ovarian cysts or in the acute setting with ovarian cyst accidents, as this marker is raised in peritonitis, hemorrhage, cyst rupture, and infection, as well as in menstruation, fibroids, and endometriosis.

The finding of an elevated CA125 level is most useful when combined with an ultrasonographic investigation while assessing a postmenopausal woman with an ovarian cyst. ^{[1, 6]}

CA125 is not useful when used alone as a single, 1-time test for ovarian cancer screening; however, it may have increased value when serial measurements are performed over time, if these measurements are incorporated into a risk of ovarian cancer algorithm (ROCA).

Additional markers for ovarian cancer

Extensive research is ongoing to find an accurate blood test for the detection of early ovarian cancer or precancer. Other markers have been investigated, including lysophosphatidic acid, tumor-associated glycoprotein 72 (TAG72), OVX1, macrophage colony-stimulating factor (M-CSF), leptin, osteopontin, insulin-like growth factor II, and macrophage inhibitory factor.

Estimation of a panel of some of these blood markers—leptin, prolactin, osteopontin, insulinlike growth factor, macrophage inhibitory factor, and CA125—is included in an immunoassay marketed under the name Ovasure. ^{[35, 36, 37]} This product is meant to aid in the assessment of whether a previously detected ovarian mass may be benign or malignant, prior to surgery.

Newer experimental markers have been identified through various laboratory techniques. These include mesothelin, human epididymis protein 4, kallikrein, and haptoglobin alpha. The use of markers in tumor marker panels may increase the sensitivity but decreases the specificity. ^[38]

Other tumor marker values may be elevated in patients with neoplastic ovarian cysts. These include serum inhibin in granulosa cell tumors, alpha fetoprotein in endodermal sinus tumors, lactic dehydrogenase in dysgerminomas, and alpha fetoprotein and beta hCG in embryonal carcinomas.

This is the primary imaging tool for a patient considered to have an ovarian cyst. ^{[1, 39, 40, 5]} Findings can help to define a cyst’s morphologic characteristics. If the ultrasonographic features are not typical of an ovarian cyst, follow-up ultrasonography can be performed to exclude ovarian neoplasm. Follow-up ultrasonography can also show resolution of a cyst. ^[41]

A normal ovary is 2.5-5 cm long, 1.5-3 cm wide, and 0.6-1.5 cm thick. In the follicular phase, several follicles are usually visible within the ovarian tissue.

On a sonogram, simple ovarian cysts have a uniformly thin, rounded wall and a unilocular appearance that is either hypoechoic or anechoic. They usually measure 2.5-15 cm in diameter, and posterior acoustic enhancement (a hyperechoic area) may be visible deep to the fluid-filled cyst. ^[2] These cysts are unlikely to be cancerous. Most commonly, they are functional follicular or luteal cysts or, less commonly, serous cystadenomas or inclusion cysts.

Complex cysts may have more than 1 compartment (multilocular), thickening of the wall, projections (papulations) sticking into the lumen or on the surface, or abnormalities within the cyst contents. Malignant cysts usually fall within this category, as do many benign neoplastic cysts.

A study by Smith-Bindman et al reported that simple cysts found with ultrasonography were not associated with an increased risk of ovarian cancer, however, complex cysts or solid masses were associated with a significant increased risk of ovarian cancer. ^[42]

Hemorrhagic cysts, endometriomas, and dermoids tend to have characteristic features on sonograms that may help to differentiate them from malignant complex cysts. A dermoid cyst is shown in the sonogram below.

Endovaginal sonogram shows a striking echogenic mass lateral to the uterus, with posterior acoustic shadowing giving a "tip-of-the-iceberg" appearance. This is pathognomonic for a dermoid cyst. Occasionally, this appearance may be mistaken for a gas-filled bowel. Courtesy of Patrick O'Kane, MD.

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Sonograms may not be helpful for differentiating hydrosalpinx, paraovarian, and tubal cysts from ovarian cysts.

Corpus luteal cysts

A corpus luteal cyst, especially in pregnancy, tends to be larger and more symptomatic than a follicular cyst and is prone to hemorrhage and rupture. On a sonogram, it has a varied appearance ranging from a simple cyst to a complex cystic lesion with internal debris and thick walls. ^[14]

A corpus luteal cyst is typically surrounded by a circumferential rim of color, referred to as the “ring of fire,” on Doppler flow. Compared with a follicular cyst, a corpus luteal cyst has thicker, more echogenic, and more vascular walls. A hemorrhagic corpus luteal cyst has a variable echogenic pattern on ultrasonography, depending on clot formation and lysis in the cyst. ^[13] Fresh blood appears acutely anechoic. There is mixed echogenicity subacutely; chronically, the blood appears anechoic again, which is consistent with clot formation, retraction, and lysis. ^[2]

Hemorrhage into the cyst appears diffuse, with a reticular pattern described as a "fishnet pattern" or "spider web" appearance. Color Doppler ultrasonography shows no vascularity within the clot, whereas a solid nodule may show vascularity.

Ovarian torsion

The ultrasonographic appearance of ovarian torsion varies, but, most commonly, the ovary is enlarged. Massive ovarian edema may be seen with torsion, as the twisting of the pedicle impedes lymphatic drainage and venous outflow, leading to ovarian enlargement.

Torsion may be intermittent and recurrent, with spontaneous detorsion, allowing arterial and venous flow to the ovary to be observed on ultrasonography. Occasionally, a twisted vascular pedicle (referred to as the "whirlpool sign") may be visible during active torsion. However this is not a sensitive finding. ^[14]

Endovaginal ultrasonography

Endovaginal ultrasonography can help in a detailed morphologic examination of pelvic structures. This requires a handheld probe to be inserted into the vagina. It is relatively noninvasive and is well tolerated in reproductive-aged women and in post–reproductive-aged women who are still engaging in intercourse. It does not require a full bladder.

Transabdominal ultrasonography

Transabdominal ultrasonography is better than endovaginal ultrasonography for evaluating large masses and their subsequent complications, such as hydronephrosis or free fluid. It also allows assessment of other intra-abdominal structures, such as the kidneys and liver, as well as an ascites if present. Transabdominal ultrasonography is best performed with a full bladder to use as an acoustic window, in order to better visualize structures. A transabdominal sonogram is shown below.

Transabdominal sonogram of a multilocular right ovarian cyst that is 24 cm in diameter, with the adjacent fallopian tube and uterus. The infundibulo-pelvic ligament carrying the ovarian artery and vein has been divided. This sonogram demonstrates a large, complex cystic mass with vascularity within the septations. Red and blue colors show blood flow towards and away from the transducer. The resistive index was low. Histology reported a mucinous cystadenocarcinoma of low malignant potential. Courtesy Patrick O'Kane, MD.

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Transvaginal ultrasonography with a higher-frequency probe allows better resolution of the ovary than a transabdominal lower-frequency probe.

3-D ultrasonography

Three-dimensional (3-D) ultrasonography may have advantages in the evaluation of ovarian cysts. ^{[43, 44]}

Doppler flow studies

These studies can help to identify blood flow within a cyst wall and adjacent areas, including the tumor surface, the septa, solid parts within the tumor, and the peritumorous ovarian stroma. The principle is that new vessels within tumors have lower resistance to blood flow because they lack developed smooth muscle in the walls. This can be quantitated into a resistive or pulsatility index.

Estimation of the resistive index has limited clinical value in premenopausal women because of the great overlap of low-resistance flow characteristics in functional tumors and early cancers.

Determination of the presence or absence of any blood flow within certain cysts may be helpful in diagnosis. For instance, hemorrhagic cysts may contain fine internal septations that characteristically do not demonstrate blood flow on Doppler images.

Cancer screening

Using ultrasonography alone as a screening tool for ovarian cancer has been shown to lead to an overall positive predictive value of only 1-27%. ^[38] Two large studies have been using a combination of ultrasonography and serum CA125 testing. ^[38]

The United Kingdom Collaborative Trial of Ovarian Cancer Screening enrolled 202,000 postmenopausal women aged 50-74 years. Women of average risk were randomized to receive an annual pelvic examination, annual ultrasonography, or CA125 measurement (including the ROCA), with ultrasonography employed in patients with elevated CA125 levels. For primary invasive epithelial ovarian and tubal cancers, CA125 measurement (plus ultrasonography if indicated) had a specificity of 99.8% and a positive predictive value of 35.1%, whereas ultrasonography alone was associated with a specificity of 98.2% and a positive predictive value of 2.8%. ^[45]

In the National Institutes of Health Prostatic, Lung, Colorectal and Ovarian (NIH-PLCO) cancer study, more than 34,000 healthy, average-risk women aged 55-74 years were randomly assigned to receive either annual CA125 testing plus vaginal ultrasonography (interventional arm) or their usual care (control arm). ^[46] In assessing the screening arm, the positive predictive value for cancer was only 1.3%.

CT scanning is more sensitive but less specific than ultrasonography in detecting ovarian cysts. The addition of CT scanning to the workup of ovarian cysts offers very little additional information and usually does not alter treatment plans. ^[20]

CT scanning is best in imaging hemorrhagic ovarian cysts or hemoperitoneum due to cyst rupture. It can also be used to distinguish other intra-abdominal causes of acute hemorrhage from cyst rupture. ^[41] In addition, CT scanning allows examination of the abdominal contents and retroperitoneum in cases of malignant ovarian disease.

CT scanning should be avoided in pregnancy, if possible, to prevent radiation exposure to the fetus. MRI is a better option in these patients when ultrasonography cannot clearly elucidate the adnexal mass.

MRI, in conjunction with ultrasonography, may provide marginal improvements in specificity, but in most cases, the additional cost in not justified. ^[20] MRI is instead reserved for cases in which ultrasonographic and CT scan findings are indeterminate in identifying a mass as an ovarian cyst safely in a pregnant patient. ^[5]

MRI scans have better soft tissue contrast than do to CT scans, particularly for identifying fat and blood products, and can provide a better idea of the organ of origin for gynecologic masses.

Simple ovarian cysts show low signal intensity with T1-weighted images and high signal intensity with T2-weighted images owing to the intracystic fluid.

Hemorrhagic cysts result in a high signal on T1-weighted images and an intermediate to high signal on T2-weighted images. Hemoperitoneum after cyst rupture appears bright on T2-weighted images and slightly hyperintense on T1-weighted images. ^[41]