e6-15: Asymptomatic Ovarian Masses

Ovarian masses are common, affecting up to 20% of women. Many of these masses are found incidentally, often as part of a radiologic work-up for another symptom, such as abdominal pain. Although the vast majority of ovarian masses in premenopausal women are benign, the incidence of ovarian cancer increases with age. Additionally, up to 10% of suspected ovarian masses may be related to nonovarian disease (see eTable 18–3 for more details). The role of the primary care clinician is to provide prompt referral to a gynecologist or gynecologic-oncologist based on the likelihood of malignancy and the need for potential surgical management.

A. Symptoms and Signs

Although many ovarian masses are discovered incidentally, patients should be asked about any potential symptoms that might be associated with ovarian malignancy, such as persistent abdominal bloating, anorexia, early satiety, pelvic or abdominal pain, or increased urinary urgency and frequency. Clinicians should also assess the patient’s underlying risk by obtaining a thorough family history, especially with regard to diagnoses of breast, uterine, colon, or ovarian cancers.

Although the physical examination is relatively insensitive for the diagnoses of ovarian masses, it is important to examine for any associated findings, such as lymphadenopathy. Palpable pelvic masses that are irregular, solid, fixed, nodular, bilateral, or associated with ascites are particularly concerning for malignancy, and should prompt urgent referral to a gynecologist.

B. Diagnostic Tests and Imaging

Serum CA-125 is a biomarker that is expressed by the majority of epithelial ovarian cancers. However, its serum level is also elevated in other benign conditions in premenopausal women, such as endometriosis, pelvic inflammatory disease, and adenomyosis. As a result, the serum CA-125, by itself, is unreliable for assessing the risk of ovarian cancer in reproductive-age women (sensitivity 50–74%, specificity 26–92%). In contrast, in postmenopausal women, the serum CA-125 is more useful for differentiating benign conditions from ovarian cancer. As a consequence, the serum CA-125 is routinely measured in the assessment of ovarian masses in postmenopausal women. A CA-125 value above 35 units/mL is considered abnormal, but rising levels on serial determinations are more helpful than a single value. Serum lactate dehydrogenase (LD), alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) may be elevated in germ cell tumors, and these markers should be ordered in premenopausal women (under age 40 years) who have complex ovarian mass on ultrasound imaging. Although measuring CA-125 can be useful in the evaluation of an ovarian mass, evidence does not support the use of serum CA-125 in routine screening for ovarian cancer in asymptomatic women.

Transvaginal ultrasound is the diagnostic test of choice in any premenopausal or postmenopausal woman presenting with an ovarian mass. Ultrasonography should be performed by clinicians with expertise in gynecologic imaging who can provide a thorough description of the morphology and ultrasonographic features of the mass.

Ultrasound detection of a simple cyst is associated with a benign process in 95–99% of postmenopausal women. Simple cysts are characterized by a round or oval shape, a thin wall, posterior acoustic enhancement, anechoic fluid, and an absence of septations or nodules. Complex cysts may have solid components, septations, and papillary projections.

Ovarian masses may be characterized according to the International Ovarian Tumor Analysis (IOTA) “rules” (http://www.iotagroup.org/), which help to differentiate benign from malignant ovarian mass processes (sensitivity 95%, specificity 91%). According to the IOTA classification, an ovarian mass is suspicious of being malignant when any of the following features are present: irregular multilocular solid tumor with largest diameter greater than 1 cm, four or more papillary structures, ascites, and prominent blood flow on color Doppler. If an ovarian mass is suspected of being malignant, the patient should be urgently referred to a gynecologic oncologist.

Ovarian masses may be benign, malignant (both primary and secondary malignancy), or nonovarian in origin. See eTable 18–3 for additional details regarding differential diagnosis.

In women with an ovarian mass, management depends on the likelihood of malignancy, as determined by radiographic features, menopausal status, and measurement of tumor markers (in appropriate patients). Strategies include conservative management, close monitoring with surveillance imaging, or referral for surgical intervention. Since the risk of ovarian cancer increases with age, a patient’s menopausal status is a critical determinant for guiding management decisions, as detailed below.

A. Premenopausal Women

Simple asymptomatic cysts that are less than 5 cm in diameter typically resolve over two or three menstrual cycles and do not require any further management. Pelvic ultrasound should be repeated yearly in women with simple cysts that are 5–7 cm in diameter. Women with larger cysts (greater than 7 cm) should be referred for gynecologic evaluation.

Premenopausal women with complex cysts or ovarian masses that have worrisome features on ultrasound should be referred for gynecologic evaluation. In these situations, measurement of the serum CA-125 may be helpful in guiding management. Serum CA-125 levels that are less than 200 units/mL may be associated with benign gynecologic conditions, such as endometriosis, whereas levels greater than 200 units/mL (and especially if rising on serial determinations) are concerning for ovarian cancer and should prompt consultation with a gynecologic oncologist.

Guidelines recommend measurement of serum LD, AFP, and hCG levels in all women under the age of 40 who present with a complex ovarian mass, in order to assess for the possibility of germ-cell tumors.

B. Postmenopausal Women

The serum CA-125 level should be measured in all postmenopausal women with an ovarian mass. This value can then be used in calculating the RMI, which has a high sensitivity and specificity for predicting the likelihood of ovarian cancer. The RMI is a product of the patient’s menopausal status, serum CA-125 level, and ultrasound score (higher scores assigned according to the presence of ascites, solid areas, metastases, multilocular and bilateral lesions). Using a cut-off value of 200, the RMI has a sensitivity of 78% and specificity of 87% for differentiating malignant from benign ovarian lesions.

If the RMI is less than 200, postmenopausal women with asymptomatic, small (less than 5 cm), unilocular, and unilateral simple cysts can be monitored with surveillance imaging. Guidelines recommend repeat assessment with a transvaginal ultrasound and CA-125 measurement in 4–6 months; masses that are enlarging or have any change in features should be referred for gynecologic evaluation and possibly surgical intervention. If the mass is stable or decreasing in size, repeat ultrasound and CA-125 measurement are recommended again in 6 months. At that time, women with a persistently stable mass on imaging and a normal CA-125 may be discharged from follow-up.

Postmenopausal women with an ovarian mass and a calculated RMI greater than or equal to 200 have an increased risk of malignancy. A CT scan of the abdomen and pelvis should be performed to more fully stage disease extent, and these women may be referred to a gynecologic oncologist for additional evaluation and possible surgery.