Residency · Residency · Obstetrics Gynecology
Ovarian Mass Evaluation and Adnexal Triage
Epidemiology
Adnexal masses are common, with 5 to 10% of women undergoing surgery for an adnexal mass during their lifetime. The majority are benign, especially in premenopausal women. Ovarian cancer accounts for approximately 20,000 new cases and 13,000 deaths annually in the United States. The risk of malignancy in an adnexal mass is 1 to 3% in premenopausal women and 30 to 40% in postmenopausal women. Accurate preoperative triage determines the appropriate surgical setting and whether specialist involvement is needed.
Differential Diagnosis of Adnexal Masses
Ovarian -- Benign
Benign ovarian masses include functional cysts (follicular and corpus luteum), endometriomas, mature cystic teratomas (dermoids), serous and mucinous cystadenomas, fibromas and thecomas, and paraovarian or paratubal cysts.
Ovarian -- Malignant
Malignant ovarian masses include epithelial ovarian cancers (serous, mucinous, endometrioid, clear cell), borderline or low malignant potential tumors, germ cell tumors (dysgerminoma, immature teratoma, yolk sac tumor), sex cord-stromal tumors (granulosa cell, Sertoli-Leydig), and metastatic disease such as Krukenberg tumors from gastrointestinal primaries or breast cancer.
Non-Ovarian
Non-ovarian adnexal masses include ectopic pregnancy, tubo-ovarian abscess, hydrosalpinx, pedunculated fibroid, peritoneal inclusion cyst, appendiceal mass, diverticular abscess, and pelvic kidney.
Ultrasound-Based Risk Stratification
Transvaginal Ultrasound (TVUS)
Transvaginal ultrasound is the first-line imaging modality for evaluating an adnexal mass. Key features to assess include laterality, size, internal composition (solid versus cystic versus mixed), septations, papillary projections, color Doppler flow, and free fluid.
Simple Cyst Criteria
A simple cyst is unilocular and thin-walled (less than 3 mm) with anechoic fluid. It has no solid components, septations, or papillary projections and no internal color Doppler flow. Size criteria are less than 10 cm in premenopausal women and less than 3 cm in postmenopausal women. Simple cysts are almost always benign with a malignancy risk below 1%.
Features Suggestive of Malignancy
Features raising concern for malignancy include a solid component or mixed solid-cystic composition, papillary projections or mural nodules, thick septations exceeding 3 mm, irregular borders, internal vascularity on color Doppler, ascites, bilateral masses, peritoneal nodularity, and large size exceeding 10 cm.
<image>Ultrasound images comparing benign and malignant adnexal mass features: a simple thin-walled anechoic cyst (benign), an endometrioma with homogeneous ground-glass echogenicity (benign), a dermoid with echogenic fat and calcification (benign), and a complex solid-cystic mass with papillary projections, thick septations, and internal color Doppler flow (suspicious for malignancy)</image>
IOTA Simple Rules
The International Ovarian Tumor Analysis group developed a classification using five benign features (B-rules) and five malignant features (M-rules). Benign features include a unilocular cyst, a solid component less than 7 mm, acoustic shadows suggesting a dermoid or fibroma, a smooth multilocular tumor less than 10 cm, and no blood flow on Doppler. Malignant features include an irregular solid tumor, ascites, four or more papillary projections, an irregular multilocular-solid tumor 10 cm or greater, and very strong blood flow. If only B-rules apply, the mass is classified as benign. If only M-rules apply, it is classified as malignant. If both or neither apply, the mass is indeterminate and should be referred for expert evaluation. The system achieves a sensitivity of 93% and specificity of 90% for malignancy.
O-RADS (Ovarian-Adnexal Reporting and Data System)
O-RADS is the ACR standardized classification for adnexal lesions on ultrasound. O-RADS 0 indicates an incomplete evaluation. O-RADS 1 denotes a normal premenopausal ovary or physiologic cyst. O-RADS 2 indicates an almost certainly benign lesion with less than 1% malignancy risk, such as a simple cyst, classic endometrioma, or dermoid. O-RADS 3 indicates low malignancy risk of 1 to 10%. O-RADS 4 indicates intermediate risk of 10 to 50%. O-RADS 5 indicates high risk of 50% or greater. Management is guided by O-RADS score and menopausal status.
| O-RADS Score | Risk Category | Malignancy Risk | Examples / Management |
|---|---|---|---|
| 0 | Incomplete | N/A | Further imaging needed |
| 1 | Normal | Physiologic | Normal ovary, physiologic cyst |
| 2 | Almost certainly benign | <1% | Simple cyst, endometrioma, dermoid; observe |
| 3 | Low risk | 1-10% | Follow-up imaging or surgery |
| 4 | Intermediate risk | 10-50% | Surgical evaluation recommended |
| 5 | High risk | ≥50% | Refer to gynecologic oncology |
Tumor Markers
CA-125
CA-125 is the most studied ovarian cancer biomarker. It is elevated above 35 U/mL in 80% of advanced epithelial ovarian cancers but only in 50% of stage I cancers. It is not specific for ovarian cancer, with elevations occurring in endometriosis, pelvic inflammatory disease, liver disease, pregnancy, peritoneal irritation, and other cancers. CA-125 is more useful in postmenopausal women, where there are fewer benign causes of elevation. It should not be used as a standalone screening test in low-risk populations.
HE4 (Human Epididymis Protein 4)
HE4 is more specific than CA-125 because it is less often elevated in benign conditions. It is less sensitive than CA-125 for advanced disease but is useful in combination with CA-125.
ROMA (Risk of Ovarian Malignancy Algorithm)
ROMA combines CA-125, HE4, and menopausal status to calculate the predicted probability of epithelial ovarian cancer and stratify patients as high or low risk.
OVA1 / Overa
These are multivariate index assays combining multiple biomarkers. OVA1 includes CA-125, transferrin, apolipoprotein A1, beta-2 microglobulin, and transthyretin. Overa is the next-generation version with improved specificity. These tests have high sensitivity but moderate specificity and are used to determine referral to a gynecologic oncologist.
Other Markers by Tumor Type
AFP is elevated in yolk sac tumor and embryonal carcinoma. Beta-hCG is elevated in choriocarcinoma and embryonal carcinoma. LDH is elevated in dysgerminoma. Inhibin A and B are elevated in granulosa cell tumors. Testosterone and DHEA-S are elevated in Sertoli-Leydig cell tumors. CEA is elevated in mucinous tumors and gastrointestinal cancers.
<image>Diagnostic algorithm for adnexal mass evaluation: starting with transvaginal ultrasound and O-RADS classification, then incorporating tumor markers (CA-125, HE4, ROMA score) based on menopausal status, leading to risk stratification as low risk (gynecologist can manage), intermediate risk (consider referral), or high risk (refer to gynecologic oncology)</image>
Management by Risk Category
Premenopausal Women
A likely functional cyst presenting as a simple cyst smaller than 5 cm is managed with observation and repeat ultrasound in 6 to 12 weeks. Most resolve spontaneously. Oral contraceptive pills do not accelerate resolution but prevent new functional cysts. Low-risk masses (O-RADS 2) such as classic endometriomas or dermoids are observed with serial ultrasound, with surgical management considered if symptomatic, growing, or larger than 5 to 6 cm. Intermediate and high-risk masses (O-RADS 3 to 5) require surgical evaluation. If malignancy is a concern, referral to a gynecologic oncologist is indicated per SGO/ACOG guidelines.
Postmenopausal Women
A simple cyst smaller than 3 cm can be observed with annual ultrasound and carries very low malignancy risk below 1%. Simple cysts 3 to 10 cm are followed with serial ultrasound every 6 months, and CA-125 is considered. Complex masses or those with solid components require surgical evaluation and referral per SGO/ACOG guidelines.
Incidental Adnexal Mass
An incidentally discovered adnexal mass is managed according to O-RADS criteria. Simple cysts smaller than 3 cm in postmenopausal women and smaller than 5 cm in premenopausal women require no follow-up per ACR recommendations.
When to Refer to Gynecologic Oncology
SGO/ACOG Referral Guidelines
In premenopausal women, referral is indicated for CA-125 above 200 U/mL, ascites, evidence of metastatic disease on imaging, or a first-degree relative with ovarian or breast cancer. In postmenopausal women, referral is indicated for CA-125 above 35 U/mL, ascites, a nodular or fixed pelvic mass, or evidence of metastatic disease. At all ages, an elevated OVA1/ROMA suggesting high risk or suspicion for advanced malignancy on imaging warrants referral.
Importance of Referral
Patients operated on by gynecologic oncologists have better staging, higher optimal debulking rates, and improved survival. Inadequate initial surgery, such as cyst rupture or incomplete staging, may compromise outcomes.
Surgical Considerations
Laparoscopic Approach
Laparoscopy is preferred for likely benign masses. The cyst is removed intact to avoid rupture and spillage, using a specimen bag for extraction. Frozen section is obtained if any concern for malignancy arises.
Ovarian Cystectomy vs. Oophorectomy
Cystectomy is preferred in premenopausal women desiring fertility if the mass appears benign. Oophorectomy is performed if the patient is postmenopausal, the mass is suspicious for malignancy, or ovarian tissue cannot be preserved. Bilateral salpingectomy for ovarian cancer risk reduction (opportunistic salpingectomy) should be discussed.
Intraoperative Frozen Section
If unexpected malignant features are encountered, frozen section is obtained. If malignancy is confirmed, gynecologic oncologist involvement for staging is essential. Frozen section accuracy is 90 to 95% concordance with final pathology.
Clinical Pearls
The majority of adnexal masses in premenopausal women are benign. Functional cysts smaller than 5 cm can be observed with repeat ultrasound in 6 to 12 weeks.
O-RADS provides a standardized framework for communicating adnexal mass risk and should be learned as a classification system.
CA-125 is more specific in postmenopausal women. In premenopausal women, many benign conditions cause elevation.
SGO/ACOG referral guidelines ensure that patients with high-risk features are operated on by gynecologic oncologists, improving outcomes.
Rupturing a suspicious cyst during surgery should be avoided. Intact removal in an endocatch bag is essential.
Opportunistic salpingectomy at the time of benign gynecologic surgery reduces future ovarian cancer risk.
Simple cysts smaller than 3 cm in postmenopausal women have less than 1% malignancy risk and can be followed conservatively.
<image>Decision tree for management of incidental adnexal mass based on menopausal status and O-RADS score, showing observation pathways for low-risk lesions and surgical or referral pathways for intermediate and high-risk lesions</image>
References
- ACOG Practice Bulletin No. 174: Evaluation and Management of Adnexal Masses (2016, reaffirmed 2023)
- SGO/ACOG Referral Guidelines for Ovarian Cancer (2023 update)
- Andreotti RF et al. O-RADS US Risk Stratification and Management System. Radiology. 2020;294:168-174
- Timmerman D et al. Simple ultrasound rules to distinguish between benign and malignant adnexal masses (IOTA). Ultrasound Obstet Gynecol. 2008;31:681-690
- ACOG Committee Opinion No. 774: Opportunistic Salpingectomy as a Strategy for Epithelial Ovarian Cancer Prevention (2019)
- Bristow RE et al. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma. J Clin Oncol. 2002;20:1248-1259
