Suspected ovarian neoplasm is a common problem in women of all ages. Women have a 5 to 10 percent risk of requiring surgery, and those who undergo surgery have a 13 to 21 percent chance of being diagnosed with ovarian cancer. The primary goal of diagnostic evaluation of adnexal masses is to exclude malignancy. When evaluating options for management, physicians often take into account the woman's age and family history. The American College of Obstetricians and Gynecologists (ACOG) has created guidelines for the management of adnexal masses. These guidelines include a review of the patient factors, physical findings, imaging results, and serum markers that help categorize masses to guide physicians in choosing the appropriate management strategy.

Diagnosing and managing adnexal masses can be problematic for physicians. Although some masses require immediate intervention, most are detected incidentally. It is the physician's role to determine whether the mass is likely to be malignant. Surgery should be performed promptly in women with masses that may be malignant. Masses that are not obviously benign or malignant typically require surgery as well; however, some can be managed laparoscopically.

The differential diagnosis of adnexal masses includes gynecologic and nongynecologic sources (Table 1). Masses in premenopausal women typically have a gynecologic source (e.g., functional cysts), whereas masses in postmenopausal women are typically benign neoplasms (e.g., cystadenomas). It should be noted that metastatic cancers can sometimes initially present as adnexal masses.

Ovarian Cancer

The lifetime risk of developing ovarian cancer is approximately one in 70. A woman with stage I ovarian cancer has a more than 90 percent five-year survival rate; however, only 20 percent of cancers are detected this early. Women who have advanced-stage cancer have a five-year survival rate of 30 to 55 percent. Over the past 20 years, there have been small improvements in mortality rates because of advances in cytoreductive surgery and more effective first and second-line chemotherapeutic agents. Risk factors for ovarian cancer include older age, family history of breast or ovarian cancer, hereditary non-polyposis colorectal cancer, Lynch II syndrome, nulliparity, primary infertility, and endometriosis.

Clinical Tests

PHYSICAL EXAMINATION

Pelvic examinations have limited ability to identify adnexal masses, especially in patients whose body mass index is greater than 30 kg per m².

ULTRASONOGRAPHY

High-frequency, gray-scale transvaginal ultrasonography can produce high-resolution images of adnexal masses and, therefore, is the most widely used imaging modality for this purpose. It is also the imaging modality of choice in asymptomatic women. Advantages of transvaginal ultrasonography include availability, cost-effectiveness, and patient tolerability. No other imaging technique has been found to be superior to ultrasonography for overall accuracy (Table 2); therefore, it is the only one recommended for routine use. When used alone, transvaginal ultrasonography may be limited by its lack of specificity and low positive predictive value for cancer; therefore, abdominal ultrasonography may be useful in conjunction with transvaginal ultrasonography to provide more accurate images of pelvic and abdominal masses.

Color Doppler ultrasonography allows measurement of blood flow in and around the mass. The ultimate goal of color Doppler ultrasonography is to increase the specificity of gray-scale, two-dimensional ultrasonog raphy. If performed in conjunction with transvaginal ultrasonography, color Doppler ultrasonography measures blood flow indices (e.g., resistive index, pulsatility index, maximum systolic velocity); however, its use is controversial because the values of these indices overlap considerably between benign and malignant masses.

OTHER IMAGING MODALITIES

Computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) are not recommended for initial evaluation of adnexal masses, and their use after transvaginal ultrasonography is of limited value. Because of their high cost, CT, MRI, and PET should be used only in special circumstances.

SERUM MARKER SCREENING

CA 125 antigen is the most extensively studied serum marker for distinguishing benign from malignant pelvic masses. It is most valuable in nonmucinous epithelial cancers; it is not useful in distinguishing other categories of ovarian malignancy. The CA 125 antigen level is elevated in 80 percent of patients with epithelial ovarian cancer; however, it is elevated in only 50 percent of patients with stage I disease. For this reason, measurement of CA 125 antigen is not a useful screening test. For distinguishing between benign and malignant masses, CA 125 antigen has a sensitivity of 61 to 90 percent, a specificity of 71 to 93 percent, a positive predictive value (PPV) of 35 to 91 percent, and a negative predictive value of 67 to 90 percent. Specificity and positive predictive value are consistently higher in postmenopausal women; CA 125 antigen elevations in these women should be considered highly suspicious for malignancy.

Recommendations

ULTRASOUND FINDINGS IN BENIGN DISEASE

A prospective trial of 2,763 postmenopausal women with unilocular cysts 10 cm or smaller who were evaluated with serial ultrasonography showed that more than two thirds of patients had spontaneous resolution. No cancers were found after a mean follow-up of 6.3 years, which indicates that malignancy risk is extremely low in this population. Therefore, simple cysts 10 cm or less in diameter are generally benign and may be monitored without intervention.

CA 125 ANTIGEN MEASUREMENT

Elevations in CA 125 antigen levels help distinguish benign from malignant masses in postmenopausal women. The few studies that evaluated the predictive value of elevated CA 125 antigen levels showed that PPV and specificity are consistently higher in postmenopausal women (PPV = 98 percent in postmenopausal women versus 49 percent in premenopausal women).

Although measurement of CA 125 antigen is less valuable for predicting cancer risk in premenopausal women, extreme values may still be helpful. Masses in premenopausal women who have normal to slightly elevated levels are typically benign. Normal levels in asymptomatic women who do not have findings suspicious for cancer on transvaginal ultrasonography can justify continued observation.

EVALUATION IN PREMENOPAUSAL WOMEN

Pelvic masses in premenopausal women are usually benign. Evaluation in this population depends on the presence or absence of symptoms; those with symptoms typically require immediate treatment. Evaluation may include a thorough medical history and physical examination, measurement Chuman chorionic gonadotropin, complete blood count, and transvaginal ultrasonography. Other studies (e.g., serial hematocrit measurements, cultures) may also be needed.

EVALUATION IN POSTMENOPAUSAL WOMEN

Because many common diagnoses found in premenopausal women (e.g., endometriosis, ectopic pregnancy) can be excluded in postmenopausal women, and because there is a greater chance of malignancy in postmenopausal women, there should be a much higher index of suspicion for malignancy in this population. Evaluation should include transvaginal ultrasonography and CA 125 antigen measurement. Most pelvic masses (excluding simple cysts) will require surgery.

Of note, the ovary is a common place for metastases from uterine, breast, colorectal, and gastric cancers. If not already performed in the past year, mammography and breast and digital rectal examinations should be done in all women with pelvic masses. If abnormal uterine bleeding is present, or if transvaginal ultrasonography shows endometrial lining thickening, an endometrial biopsy should be done. To rule out gastric and colon cancers, upper and lower gastrointestinal endoscopy should be performed in patients who are anemic or older than 50 years, or who have a positive fecal occult blood test.

ASPIRATION OF CYST FLUID

Aspiration of nonunilocular cyst fluid for diagnosis and treatment of adnexal masses is typically contraindicated in postmenopausal women, especially in patients with potentially malignant masses. Diagnostic cytology has poor sensitivity for detecting malignancy (25 to 82 percent). In addition, aspiration is not always therapeutic, even with benign masses, and aspiration of malignant masses can induce spillage or seeding of cancer cells into the peritoneal cavity, changing the stage and prognosis. Spillage at the time of surgery appears to decrease overall survival rates in patients with stage I cancer compared with patients with intact tumors. However, in patients who are unfit to undergo surgery and who have clinical and radiographic evidence of advanced ovarian cancer, aspiration can be performed to confirm the cancer diagnosis.

REPEAT IMAGING

Repeat imaging is recommended if there is uncertainty regarding a diagnosis, or when cancer or benign neoplasm is part of the differential diagnosis. In women who are at substantial risk of perioperative morbidity and mortality, repeat imaging may be safer than immediate surgical intervention. The frequency of repeat imaging has not been determined.

REFERRAL TO A GYNECOLOGIC ONCOLOGIST

Women with ovarian cancer who are treated by physicians who have advanced training and expertise in gynecologic cancer (e.g., gynecologic oncologists) have better survival rates than women treated by physicians without such training or expertise. These improved rates are a result of proper staging, which helps identify patients with unexpected occult metastasis who need adjuvant chemotherapy, and of aggressive debulking of advanced disease. The Society of Gynecologic Oncologists and ACOG have created referral guidelines for patients with newly diagnosed pelvic masses (Table 3).

MANAGEMENT IN PREGNANCY

There are few data available on managing adnexal masses in patients who are pregnant. The prevalence of adnexal masses in pregnancy ranges from 0.05 to 3.2 percent of live births. Common diagnoses include mature teratomas and paraovarian or corpus luteum cysts. Rates of malignancy range from 3.6 to 6.8 percent of persistent masses, with most malignancies being germ cell or stromal tumors, or epithelial tumors with low malignancy potential.

The recommended evaluation of pregnant patients with pelvic masses is similar to that of premenopausal women; however, imaging will depend on gestational age. Abdominal ultrasonography can be used in addition to transvaginal ultrasonography in women who are farther along in their pregnancy because the ovaries may be outside of the pelvis later in gestation. If additional imaging is needed, MRI is the modality of choice because it does not expose the fetus to radiation. CA 125 antigen levels reach their highest elevation in the first trimester and then gradually decrease; therefore, low-level elevations during pregnancy typically are not associated with malignancy.

Surgical removal of persistent masses in the second trimester is common; however, data supporting this practice are lacking. Persistent masses are typically larger than 5 cm and have complex morphology on transvaginal ultrasonography. The actual occurrence of acute complications has been reported to be less than 2 percent, and approximately 51 to 70 percent of masses spontaneously resolve during pregnancy. Most masses in pregnant women appear to have low risk of malignancy and acute complications; therefore, expectant management can be considered.

LAPAROTOMY VS. LAPAROSCOPY

Laparoscopy is typically considered to be contraindicated in patients with masses suspicious for cancer based on transvaginal ultrasound findings, CA 125 antigen levels, and clinical assessment. Retrospective studies have shown that laparoscopy has low complication rates (0 to 10 percent); however, rates are higher if the mass is suspicious for cancer. Women who undergo laparoscopy typically have shorter hospital stays, decreased pain, and decreased convalescence time compared with those who undergo laparotomy. Laparotomy and laparoscopy have equal rates of intraoperative cyst rupture, but laparoscopy results in significantly decreased operative time, perioperative morbidity, length of hospital stay, and postoperative pain.

HYSTERECTOMY AND OOPHORECTOMY

The extent of surgery usually depends on the diagnosis, patient's age, and the patient's desire for ovarian function or fertility. Cystectomy is the operation of choice in premenopausal women. Unilateral oophorectomy or salpingo-oophorectomy is indicated in patients in whom ovarian tissue cannot be preserved. The patient should be informed of the risk of bilaterality, which is approximately 2 to 3 percent for benign mucinous tumors, 15 percent for benign teratomas, and up to 25 percent for benign serous tumors. Perimenopausal and postmenopausal women can also undergo cystectomy or unilateral salpingo-oophorectomy; hysterectomy or bilateral salpingo-oophorectomy are also appropriate after completion of childbearing, and may reduce the risk of future pelvic surgery. It is unknown if the benefits for preserving the ovaries outweigh the risk of leaving them in situ.

CONSERVATIVE SURGERY IN OVARIAN CANCER

Standard management of gynecologic cancer includes hysterectomy with bilateral salpingo-oophorectomy and staging procedures. Unilateral salpingo-oophorectomy and ovarian cystectomy do not appear to be associated with comprised prognosis in patients with germ cell tumors; stage I stromal tumors; tumors with low malignancy potential; and stage IA, grade 1 or 2 invasive cancer. These patients should undergo complete surgical staging even if they choose to preserve the uterus and remaining ovary. Recurrence rates are low in patients with tumors with low malignancy potential (0 to 18.5 percent) and in patients with stage IA, grade 1 or 2 tumors (9.6 to 14.7 percent). Long-term survival rates are greater than 90 percent for all tumor types, and reproductive outcomes are typically favorable.