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 workup 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 found in Chapter 18-21: Ovarian Cancer & Ovarian Tumors 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 regarding 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 initial diagnostic test of choice in any premenopausal or postmenopausal woman presenting with an ovarian mass. Transvaginal ultrasound has a reported sensitivity of 93.5% and specificity of 91.5% in separating masses that are likely benign from those that are concerning for malignancy and require further evaluation.

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. In 2020, the American College of Radiology developed the Ovarian-Adnexal Reporting and Data System (O-RADS), which applied the IOTA criteria to standardize the reporting of ovarian findings in ultrasound imaging reports and the process of communicating risk of malignancy to providers:

• Incomplete evaluation (O-RADS 0): adnexal lesions are incompletely characterized due to technical limitations; repeat imaging using ultrasound or MRI as needed.

• Normal ovary (O-RADS 1): 0% risk of malignancy. Simple cysts less than or equal to 3 cm or corpus luteum less than or equal to 3 cm.

• Almost certainly benign (O-RADS 2): Less than 1% risk of malignancy. Simple cysts greater than 3 cm but less than 10 cm; classic benign lesions less than 10 cm (ie, mature teratoma, hemorrhagic cysts, endometrioma); non-simple unilocular cyst less than 10 cm.

• Low risk malignancy (O-RADS 3): 1–10% risk of malignancy. Mature teratoma/hemorrhagic cysts/endometriomas greater than or equal to 10 cm; unilocular cysts with irregular inner wall; multilocular cyst less than 10 cm with smooth inner wall, vascularity color score 1–3; solid smooth lesion of any size with color score of 1.

• Intermediate risk (O-RADS 4): 10–50% risk of malignancy. Unilocular cyst with solid component (0–3 papillary projections). Multilocular cysts: greater than 10 cm with smooth inner wall, color score 1–3; any size with smooth inner wall and color score 4; any size with irregular inner wall or septation, or both, any color score; with solid component color score 1–2. Solid smooth lesions, any size, color score 2–3.

• High risk (O-RADS 5): greater than 50% risk of malignancy. Unilocular cyst with greater than or equal to 4 papillary projections and any color score. Multilocular cyst with solid component and color score 3–4. Solid smooth lesion, color score 4. Solid irregular lesion, any color score. Peritoneal findings such as ascites or nodules.

If an ovarian mass is suspected of being malignant (O-RADS 4 or 5), the patient should be referred urgently to a gynecologic oncologist. Masses categorized as O-RADS 3 are usually managed by general gynecologists.

Serum CA-125 is a biomarker that is expressed by most 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 some utility in differentiating benign conditions from ovarian cancer. A CA-125 value above 35 U/mL is considered abnormal in postmenopausal women, although rising levels on serial determinations are more helpful than a single value.

Serum 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 found in Chapter 18-21: Ovarian Cancer & Ovarian Tumors for additional details regarding differential diagnosis.

Management of an ovarian mass 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, menopausal status is a critical determinant for guiding management decisions, as described 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 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 or O-RADS score 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 U/mL may be associated with benign gynecologic conditions, such as endometriosis, whereas levels greater than 200 U/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 younger than 40 years who present with a complex ovarian mass, 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 Risk for Malignancy Index greater than or equal to 200 have an increased risk of malignancy, and urgent referral to a gynecologic oncologist for additional evaluation and possible surgery is appropriate.