Approach
A common clinical scenario for physicians is the incidental finding of an ovarian cyst on ultrasonography performed as routine or for other indications. Whether a woman presents with an acute abdomen or without any symptoms, the ultimate goals of diagnosis are to identify a cyst, and to determine the risk of malignancy and the necessity and timing of surgical intervention.[26] Age and menopausal status represent two critical components from the patient history that impact the diagnostic algorithm of choice. The various patient populations that present with ovarian cysts and require individualised diagnostic modalities include women with an acute abdomen or shock, post-menopausal women, pre-menopausal women, and adolescents.
Women presenting in shock or with an acute abdomen
Acutely unwell women with vital sign abnormalities, signs of shock, and an acute abdomen should prompt the clinician to consider an ovarian cyst that has twisted and undergone torsion.
After a brief focused history and physical examination, which includes a thorough pelvic examination, a transvaginal ultrasound should be ordered as the first diagnostic test. The most common sonographic finding in ovarian torsion is ovarian enlargement.[27] Other findings, such as free fluid in the peritoneum, septations and debris within a complex mass, and peripheral cystic structures, are occasionally seen.
Venous flow abnormalities on Doppler ultrasonography also support a diagnosis of ovarian torsion.[27] Abdominal pain in association with ovarian enlargement and absence of ovarian venous flow on Doppler ultrasound should prompt surgical exploration for possible ovarian torsion. Ultrasound can yield important information, but this should not be relied on in isolation when the clinical picture is concerning and surgical exploration is warranted.
If the patient's clinical picture suggests torsion but the ultrasound is non-diagnostic, the next diagnostic modality is laparoscopy, which is not only diagnostic but therapeutic as well. Histopathology of the ovary can be performed to confirm the nature of the cyst.
Post-menopausal women
Assessment of malignancy risk is essential. The importance of accurate surgical staging and cytoreductive surgery for improved outcomes in ovarian cancer makes this determination crucial.
Assessment should begin with a thorough history evaluating the presence of abdominal/pelvic pain, bloating, increasing abdominal girth, early satiety, or urinary frequency/urgency. Two case-control studies have shown significant association of these symptoms with ovarian cancer, particularly when symptom duration had been <12 months and frequency had been >12 times per month.[28]
The pelvic and bimanual examinations have poor sensitivity and are, therefore, limited screening tools.[29] In the US, the Department of Health and Human Services and the National Cancer Institute do not endorse them as screening tests for ovarian cysts. The presence of the above symptoms, or concern that the pelvic examination did not provide adequate adnexal evaluation, should prompt an ultrasound examination of the pelvis.
Availability, cost-effectiveness, patient tolerability, high interobserver agreement, and excellent sensitivity make transvaginal ultrasonography the sole imaging modality of choice.[30][31] The specificity of the test alone is poor in differentiating malignancy from benign cysts. The DePriest ultrasound morphology index based on tumour volume, wall structure, and septal structure yields a negative predictive value of 100% when the score is <5.[32] Positive predictive value for malignancy is 45%.
Two-dimensional power Doppler imaging can be utilised at the time of sonography to investigate vascular characteristics of the cyst and further improve sensitivity and specificity of malignancy.[32][33]
Computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography scanning do not add further diagnostic capability in differentiating benign from malignant masses, and high cost precludes ordering these tests routinely.[1][31] MRI may improve specificity for malignancy at the expense of sensitivity.[34]
The cancer antigen (CA)-125 tumour marker is elevated in 80% of women with epithelial ovarian cancer and should be the next test obtained.[31] This is not a screening test, as only 50% of patients with stage 1 disease demonstrate elevations. Post-menopausal women with elevations of CA-125 above the upper limit of normal (35 U/mL) and pre-menopausal women with markedly elevated values (>200 U/mL) warrant concern for malignancy.[35] If serum CA125 is 35 U/mL or greater, arrange an ultrasound scan of the abdomen and pelvis.[36] Measuring the level of the HE4 biomarker in addition to the CA-125 biomarker can more correctly identify benign disease.[37]
Finally, the integration of all the above information into a risk of malignancy index (RMI) assists in differentiating benign from malignant cysts, with a sensitivity of 78% and specificity of 87% when using a score with a threshold of 200.[30] This scoring system incorporates menopausal status (M), ultrasound morphology (U), and serum CA-125 into an equation resulting in the ability to categorise women with an ovarian cyst into low risk, moderate risk, or high risk of malignancy.[30]
RMI = U x M x CA-125
Ultrasound scans are scored 1 point for each of the following characteristics:
Multilocular cyst
Evidence of solid areas
Evidence of metastases
Presence of ascites
Bilateral lesions.
U = 0 (for ultrasound score of 0)
U = 1 (for ultrasound score of 1)
U = 3 (for ultrasound score of 2 to 5).
M = 3 for all post-menopausal women dealt with by this guideline.
CA-125 is serum CA-125 measurement in U/mL.
Low-risk RMI = <25 (40% of women; risk of cancer is <3%).
Moderate-risk RMI = 25 to 250 (30% of women; risk of cancer is 20%).
High-risk RMI = >250 (30% of women; risk of cancer is 75%).
Fine needle aspiration and cytology of ovarian cyst fluid is not recommended because of poor sensitivity (25% to 82%), negative predictive value, and concern regarding possible tumour seeding the needle tract.[38] If laparotomy and oophorectomy is performed, histopathology of the ovary will confirm the nature of the cyst.
Pre-menopausal women
Much of the diagnostic strategy mimics that for post-menopausal women. A woman is considered pre-menopausal up to 1 year after cessation of menses.[1] The majority of ovarian cysts in this age group are benign, but the diagnostic algorithm follows that for post-menopausal women, with the exception of CA-125. This serum marker yields little because elevated levels are associated with many benign conditions, such as uterine fibroids, pelvic inflammatory disease (PID), endometriosis, adenomyosis, pregnancy, and menstruation. Assessment should begin with a thorough history, including a detailed personal and family history for breast, gynaecological, and colon cancer, and physical examination. Investigation for the early detection of ovarian cancer with transvaginal ultrasound or tumour markers, either alone or in combination, are not shown to reduce mortality in women who are at average risk, and may result in false positive results that lead to invasive diagnostic tests.[39]
Transvaginal ultrasonography is recommended for assessment of an adnexal mass.[26][31] Two-dimensional power Doppler imaging, which has a demonstrated diagnostic performance over standard colour Doppler, should be considered to evaluate the vascular features of a complex mass.[40] Several benign aetiologies (endometriomas, PID, cystic teratomas, and hydrosalpinx) may lead to false-positive interpretations on sonography.
The routine use of MRI for assessment of ovarian masses does not improve the sensitivity or specificity obtained by transvaginal ultrasound in the detection of ovarian malignancy.[41] In one series, MRI correctly classified all cystic teratomas and endometriomas, resulting in a false-positive rate of only 16%.[34] Negative MRI results do not rule out early-stage or borderline ovarian cancer, and all masses that appear suspicious on ultrasound require surgical evaluation with histopathology to confirm the nature of the cyst.[40][42]
If a mass contains septations, cystic and solid components, or frank solid architecture on CT or MRI, the next diagnostic strategy is to draw the germ cell tumour markers: CA-125, alpha-fetoprotein, beta-human chorionic gonadotrophin (beta-hCG), and lactate dehydrogenase (LDH).[31]
Pregnancy
Many ovarian cysts will be detected by routine ultrasonography in the first or second trimester of pregnancy. Serial ultrasonography is performed to monitor growth and torsion. Absent venous blood flow on Doppler ultrasound indicates concern for torsion. Growth that accelerates rapidly, or continues after 16 to 20 weeks, may identify cysts that will continue to complicate the duration of pregnancy.
Adolescents
Ovarian cysts present a diagnostic challenge among females aged 10 to 19 years, because benign neoplasms outnumber malignant masses and the clinical picture is usually non-diagnostic.[43][44]
In adolescent women with lower abdominal pain, a thorough clinical work-up, including abdominal examination, bimanual examination, and rectal examination, should be undertaken. Obtaining vital signs and initial full blood count is important to ensure clinical stability.
Ultrasound examination (both transabdominal and transvaginal) remains the initial diagnostic test of choice. In one study of 44 adolescents presenting with such symptoms, ultrasound was 100% accurate in the diagnosis of ovarian pathology.[43]
To specifically identify malignancy risk, colour Doppler sonography and CT or MRI can provide additional information; however, they are selectively employed in cases where uncertainty lingers after ultrasonography. MRI may specifically aid in soft tissue characterisation.
Evaluation of vessel distribution and vascular flow by colour Doppler increases the diagnostic detection of malignancy. If a mass contains septations, cystic and solid components, or frank solid architecture on CT or MRI, the next diagnostic strategy is to draw the germ cell tumour markers: CA-125, alpha-fetoprotein, beta-hCG, and LDH.[31]
Approximately 20% of all ovarian cysts in this age group stem from the germ-cell lineage, but <5% are malignant.[45] No studies have been identified that detail the association of such germ-cell tumour markers with diagnosis of actual pathology.
Among pre-menarchal patients with a suspicious ovarian cyst, a karyotype should be obtained to confirm a XX chromosome complement and rule out an undescended testis in a genotypic male with androgen insensitivity.[43]
After the above work-up is complete, surgical exploration can be undertaken for those patients with cysts that appear suspicious for a non-physiological aetiology. However, conservative surgical therapy should be employed to preserve ovarian function.
Emerging tests
Ovarian cancer risk in women with an ovarian mass (for which surgery is planned) can be assessed using an algorithm (ovarian adnexal mass assessment score test system) that incorporates the results of 5 serum biomarkers (transthyretin [prealbumin)], apolipoprotein A-1, beta-2 microglobulin, transferrin, and CA-125) with information regarding menopausal status. Early Detection Research Network, National Cancer Institute: OVA1 Opens in new window The test is not intended as a screening or stand-alone diagnostic assay.
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