e6-16: 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, or associated with ascites are particularly concerning for malignancy and should prompt urgent referral to a gynecologic oncologist.

B. Diagnostic Tests and Imaging

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" (https://www.iotagroup.org/), which help 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 solid tumor, 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.

Serum CA-125 is a biomarker that is expressed by the majority of epithelial ovarian cancers. However, in premenopausal women, its serum level can also be elevated in benign conditions, such as endometriosis, pelvic inflammatory disease, and adenomyosis making it unreliable in the assessment of the risk of ovarian cancer (sensitivity 50–74%, specificity 26–92%). In contrast, in postmenopausal women, serum CA-125 does have utility in differentiating benign conditions from ovarian cancer. A CA-125 value above 35 units/mL is considered abnormal in postmenopausal women, though 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.

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). 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. Strategies include conservative management, close monitoring with surveillance imaging, or referral for surgical intervention.

A. Premenopausal Women

Premenopausal women with simple, asymptomatic cysts can be reassured that the risk of cancer is very low; in one large case series, there were no cancers identified in premenopausal women with simple cysts of any size at 3 years of follow-up. Cysts that are less than 5 cm in diameter typically resolve over two or three menstrual cycles and do not require any further management. Serial ultrasound should be repeated in women with cysts up to 10 cm in diameter; women with larger cysts may be referred for gynecologic evaluation.

Premenopausal women with complex cysts or ovarian masses with worrisome ultrasonographic features based on the IOTA criteria above 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 (particularly 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

Serum CA-125 level should be measured in all postmenopausal women with an ovarian mass. This value can then be used to calculate the Risk for Malignancy Index, which has a high sensitivity and specificity for predicting the likelihood of ovarian cancer. The Risk for Malignancy Index 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) (https://www.nice.org.uk/guidance/cg122/chapter/Appendix-Risk-of-malignancy-index-RMI-I). Using a cut-off value of 200, the Risk for Malignancy Index has a sensitivity of 78% and specificity of 87% for differentiating malignant from benign ovarian lesions.

If the Risk for Malignancy Index 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 need 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.