Ovarian Cysts Workup

• No laboratory tests are diagnostic for ovarian cysts. However, keep in mind the possibility of cancer when managing an ovarian cyst.^[9]
• Cancer antigen 125 (CA125) is a protein expressed on the cell membrane of normal ovarian tissue and ovarian carcinomas.

  • A serum level of less than 35 U/mL is considered normal. In some laboratories, the upper limit of normal may be lower than this.
  • While CA125 values are elevated in 85% of patients with epithelial ovarian carcinomas, overall, the value is elevated in only 50% of patients with stage I cancers confined to the ovary.^[10] CA125 levels are also elevated in patients with some benign conditions or other malignancies and in 6% of healthy patients.
  • The finding of an elevated CA125 level is most useful when combined with an ultrasonographic investigation while assessing a postmenopausal woman with an ovarian cyst.
  • CA125 is not useful when used alone as a single, one-time test for ovarian cancer screening; however, it may have increased value when serial measurements are performed over time if it is incorporated into a risk of ovarian cancer algorithm (ROCA).
• Extensive research is ongoing to find an accurate blood test for the detection of early ovarian cancer or precancer. Other markers have been investigated, including lysophosphatidic acid, tumor-associated glycoprotein 72 (TAG 72), OVX1, macrophage colony-stimulating factor (M-CSF), leptin, osteopontin, insulinlike growth factor II and macrophage inhibitory factor. Newer experimental markers have been identified through various laboratory techniques. These markers include mesothelin, human epididymis protein 4, kallikrein, and haptoglobin-alpha. The use of markers in tumor marker panels may increase the sensitivity but decreases the specificity.^[11]
• Extensive research is ongoing to find an accurate blood test for the detection of early ovarian cancer or precancer. Estimation of a panel of blood markers (leptin, prolactin, osteopontin, insulinlike growth factor, macrophage inhibitory factor, and CA125) is included in an immunoassay marketed with the name Ovasure.^{[12, 13, 14]} This is marketed as a test to help diagnose whether a previously detected ovarian mass may be benign or malignant prior to surgery.
• Other tumor marker values may be elevated in patients with neoplastic ovarian cysts. These markers include serum inhibin in granulosa cell tumors, alpha-fetoprotein in endodermal sinus tumors, lactic dehydrogenase in dysgerminomas, and alpha-fetoprotein and beta-hCG in embryonal carcinomas.

• Ultrasonography

  • This is the primary imaging tool for a patient considered to have an ovarian cyst.^{[8, 15, 16]} Findings can help define morphologic characteristics of ovarian cysts.
  • Simple cysts are unilocular and have a uniformly thin wall surrounding a single cavity that contains no internal echoes. These cysts are unlikely to be cancerous. Most commonly, they are functional follicular or luteal cysts or, less commonly, serous cystadenomas or inclusion cysts.
  • Complex cysts may have more than one compartment (multilocular), thickening of the wall, projections (papulations) sticking into the lumen or on the surface, or abnormalities within the cyst contents. Malignant cysts usually fall within this category, as do many benign neoplastic cysts.
  • Hemorrhagic cysts, endometriomas, and dermoids tend to have characteristic features on sonograms that may help to differentiate them from malignant complex cysts. A dermoid cyst is shown in the sonogram below. Endovaginal sonogram shows a striking echogenic mass lateral to the uterus, with posterior acoustic shadowing giving a "tip-of-the-iceberg" appearance. This is pathognomonic for dermoid cyst. Occasionally, this appearance may be mistaken for gas-filled bowel. Courtesy of Patrick O'Kane, MD.
  • Sonograms may not be helpful for differentiating hydrosalpinx, paraovarian, and tubal cysts from ovarian cysts.
  • Endovaginal ultrasonography can help in a detailed morphologic examination of pelvic structures. This requires a handheld probe to be inserted into the vagina. It is relatively noninvasive and is well tolerated in reproductive-aged women and post–reproductive-aged women who are still engaging in intercourse. It does not require a full bladder.
  • Transabdominal ultrasonography is better than endovaginal ultrasonography for evaluating large masses and allows assessment of other intra-abdominal structures such as the kidneys, liver, and ascites. It requires a full bladder. Transabdominal sonogram is shown in the image below. Transabdominal sonogram of a 24-cm diameter multilocular right ovarian cyst with adjacent Fallopian tube and uterus. The infundibulo-pelvic ligament carrying the ovarian artery and vein has been divided. This sonogram demonstrates a large, complex, cystic mass with vascularity within the septations. Red and blue colors show blood flow towards and away from the transducer. The resistive index was low. Histology reported a mucinous cystadenocarcinoma of low malignant potential. Courtesy Patrick O'Kane, MD.
  • 3-dimensional ultrasonography may have advantages in the evaluation of ovarian cysts.^{[17, 18]} Doppler flow studies
  • These studies can help identify blood flow within a cyst wall and adjacent areas, including tumor surface, septa, solid parts within the tumor, and peritumorous ovarian stroma. The principle is that new vessels within tumors have lower resistance to blood flow because they lack developed smooth muscle in the walls. This can be quantitated into a resistive or pulsatility index.
  • Estimation of the resistive index has limited clinical value in premenopausal women because of the great overlap of low-resistance flow characteristics in functional tumors and early cancers.
  • Determination of the presence or absence of any blood flow within certain cysts may be helpful in diagnosis. For instance, hemorrhagic cysts may contain fine internal septations that characteristically do not demonstrate blood flow on Doppler images.
  • Using ultrasonography alone as a screening tool for ovarian cancer has been shown to lead to an overall positive predictive value of only 1-27%.^[11] Two large studies are using a combination of ultrasonography and serum CA125 testing.^[11] The United Kingdom Collaborative Trial of Ovarian Cancer Screening has enrolled 202,000 postmenopausal women aged 50-74 years. Women of average risk have been randomized to receive either annual pelvic examination, annual ultrasonography, or CA 125 measurement (including the ROCA), with ultrasonography for elevated CA125 levels.^[19] CA 125 measurement (plus ultrasonography if indicated) had a specificity 99.8% and positive predictive value of 35.1%, whereas ultrasonography alone was associated with a specificity of 98.2%.
  • In the National Institutes of Health Prostatic, Lung, Colorectal and Ovarian (NIH-PLCO) cancer study more than 34,000 healthy average risk women aged 55-74 years have been randomly assigned to receive either annual CA 125 testing plus vaginal ultrasonography (interventional arm) or their usual care (control arm).^[20] The primary outcome measure is mortality from ovarian and fallopian tube cancer and requires longer follow-up for analysis. In assessing the screening arm, the positive predictive value was only 1.3%
• MRI

  • MRI with gadolinium allows clearer evaluation of lesions deemed indeterminate after performing ultrasonography.
  • MRI images have better soft tissue contrast compared to CT scan images, particularly for identifying fat and blood products, and can give a better idea of the organ of origin of gynecologic masses.
  • MRI is not necessary in most cases.
• CT scan

  • CT scanning is inferior to ultrasonography and MRI for helping define ovarian cysts and pelvic masses.
  • CT scan allows examination of the abdominal contents and retroperitoneum in cases of malignant ovarian disease.

• Using needle aspiration to obtain fluid for cytologic examination provides inaccurate cytology results, and needle aspiration is an inappropriate method for cyst drainage in most cases.^{[21, 22, 23]}
• Performing diagnostic laparoscopy may sometimes be necessary to inspect a suggestive adnexal cystic mass, but an intraovarian malignancy may be missed.

The definitive diagnosis of all ovarian cysts is made based on histological analysis. Each type has characteristic findings.