Adnexal Tumors

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Background

The normal functioning ovary produces a follicular cyst 6-7 times each year. In most cases, these functional cysts are self-limiting and resolve within the duration of a normal menstrual cycle. In rare situations, a cyst persists longer or becomes enlarged. At this point, it represents a pathological adnexal mass.

Adnexal masses present a diagnostic dilemma; the differential diagnosis is extensive, and most masses are benign.[1, 2, 3] However, without histopathologic tissue diagnosis, a definitive diagnosis is generally precluded. Physicians must evaluate the likelihood of a concerning pathologic process using clinical and radiologic information and balance the risk of surgical intervention for a benign versus malignant process.

Since ovaries produce physiologic cysts in menstruating women, the likelihood of a benign process is higher in women of reproductive age. In contrast, the presence of an adnexal mass in prepubertal girls and postmenopausal women heightens the risk of a malignant neoplastic etiology.

History of the Procedure

In the past, physicians relied on the findings of a pelvic examination to diagnose an adnexal mass. With the introduction of imaging modalities including transabdominal and vaginal ultrasonography,[4] Doppler color scans, and MRI, more characterization of the internal structure of the mass (ie wall complexity, mass contents) is possible.[5, 6, 7, 8] Although not definitive, these findings can help determine whether a mass appears more consistent with a physiologic cyst or neoplastic process.

Problem

The following masses pose the greatest concern:

Epidemiology

Frequency

Determining the true frequency of adnexal masses is impossible because most adnexal cysts develop and resolve without clinical detection. When assessing the clinical significance of an adnexal mass, consideration of several age groups is important.

In girls younger than 9 years, 80% of ovarian masses are malignant and are generally germ cell tumors.[9, 10] During adolescence, 50% of adnexal neoplasms are mature cystic teratomas (often known as dermoid cysts). Women with gonads that contain a Y chromosome have a 25% chance of developing a malignant neoplasm (most commonly a dysgerminoma). Endometriosis is uncommon in adolescent women but may be present in as many as 50% of those who present with a painful mass. In sexually active adolescents, one must always consider a tubo-ovarian abscess as the cause of an adnexal mass.[11, 12]

In women of reproductive age who have had adnexal masses removed surgically, most are benign cysts or masses. Ten percent of masses are malignant[13] ; though in patients younger than 30 years many are of low malignant potential. Thirty-three percent are mature cystic teratomas, and 25% are endometriomas. The rest are serous or mucinous cystadenomas or functional cysts.

Historically, postmenopausal women with clinically detectable ovaries were thought to be at great risk of having a malignant neoplasm. With the increasing prevalence of radiologic testing, many smaller, simple cystic masses have been identified; therefore, the risk of malignancy may be only 20-30%. The differential diagnosis includes benign cysts; metastatic versus primary ovarian malignancies; tubal cysts; and neoplasms such as paratubal cysts, hydrosalpinx, or, rarely, fallopian tube cancer. Radiologic testing allows the architecture of the mass to be evaluated, which decreases the need to operate on benign masses in this age group.

Overall, approximately 10% of ovarian cancers are hereditary. As such, patients with a history suggestive of a hereditary breast-ovarian cancer syndrome (BRCA1 or BRCA2) or hereditary nonpolyposis colorectal cancer syndrome (HNPCC or Lynch syndrome) are at increased risk for developing a malignant mass.[14]  The Patient Protection and Affordable Care Act mandates that genetic counseling and testing for BRCA mutations be covered as a preventative service in high-risk individuals. The National Comprehensive Cancer Network, Society for Gynecologic Oncology, American Society of Breast Surgeons, and American College of Medical genetics each have distinct criteria for referral to genetic counseling.[15, 16, 17] All include women with high-grade serous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer at any age, as recent data suggest that as many as 16-21% of these women have a germline mutation in BRCA1 or BRCA2.[18, 19, 20]

In all age groups, the physician must also consider the possibility of uterine masses or structural deformities. Pregnancy-related adnexal masses, including ectopic pregnancy, theca lutein cysts, corpus luteum cysts, and luteomas, must be considered in all premenopausal women.[21, 22]

Pathophysiology

The pathophysiology is not well understood for most adnexal masses; however, some theories have been proposed. Functional cysts may be the result of variation in normal follicle formation. Mature cystic teratoma may be the result of abnormal germ cell proliferation. Endometriomas are thought to result from retrograde menstruation or coelomic metaplasia. The exact cause of epithelial neoplasms is unknown, but recent studies have suggested a complex series of molecular genetic changes is involved.

Presentation

The clinical presentation of an adnexal mass can be variable, but patients are often asymptomatic. Patients may present with masses that are found (1) at the time of a pelvic examination, (2) at the time of a radiologic examination for another diagnosis, or (3) at the time of a surgical procedure. Women who have symptoms may note urinary frequency, pelvic or abdominal pressure, and bowel habit changes due to the mass effect on these organs. Girls younger than 10 years frequently present with pain, as do older women who have infected masses or endometriosis. Adnexal torsion classically presents with acute abdominal pain, requiring urgent surgical intervention.

As the adnexa are located deep in the pelvis, masses may be palpated with a standard gynecologic examination. Findings such as size greater than 10 cm, nodularity, irregular adnexal contour, or fixed position are suggestive of malignancy. However, other factors, such as obesity and size of mass, may limit the accuracy of physical examination.[23]

Since many patients with adnexal masses are asymptomatic, there has been extensive research into effective screening strategies for ovarian cancer. The most widely studied potential screening test is the serum measurement of cancer antigen 125 (CA-125). CA-125 is expressed by tissues derived from coelomic and müllerian epithelia, and levels are elevated in at least 80% of females with advanced epithelial ovarian cancers. However, single-point CA-125 measurements are limited by both a lack of sensitivity (low in early-stage malignancy) and specificity (it is produced by many other nonmalignant conditions).

The largest screening trial performed to date (The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Randomized Controlled Trial, or PLCO Trial) found that among the general population, screening with CA-125 and transvaginal ultrasound versus usual care did not decrease ovarian cancer mortality. The study also reported serious complications arising from diagnostic interventions performed to evaluate false-positive screening results.[24]

While many other screening algorithms are being actively investigated, at this time there is insufficient evidence to support the routine use of pelvic ultrasound and/or CA-125 to screen for ovarian cancer in the general population. As with all screening tests, the ideal screening algorithm will ultimately balance the accurate detection of ovarian malignancy at an early stage while minimizing unnecessary interventions in patients.

Indications

Most adnexal masses resolve spontaneously over time; therefore, care must be taken to not overreact to such a finding. Surgeons who rush women with small, asymptomatic masses into surgery often create more pathology than they cure. Any surgery performed on adnexal structures can result in impaired fertility.

On the other hand, these same asymptomatic masses can be early ovarian cancers that require immediate attention. The use of radiologic testing often helps determine which women require attention (see Imaging Studies). Serum testing of CA-125 can be used in combination with radiologic testing to stratify the risk of adnexal masses. However, it is important to recognize the limitations of this serum marker. A large Swedish study has shown that approximately 50% of women with stage I ovarian cancer have a normal CA-125 test value. In addition, a high false-positive rate can be caused by pregnancy, endometriosis, cirrhosis, and pelvic or other intra-abdominal infections.[25, 26, 27] CA-125 screening does not add useful information for specific diagnosis of benign adnexal tumors except for endometrioma. An elevated level significantly increases the probability of such a lesion.[28]

Relevant Anatomy

The term adnexa is derived from the pleural form of the Latin word meaning "appendage." The adnexa of the uterus include the ovaries, fallopian tubes, and structures of the broad ligament. Most frequently, adnexal masses refer to ovarian masses or cysts; however, paratubal cysts, hydrosalpinx, and other nonovarian masses are also included within the broader definition of adnexal masses.

Several other anatomical structures are important to identify, both for the evaluation of other sources of masses within the pelvis and during surgical procedures to prevent damage to nearby organs and structures. The uterus is central to both adnexal regions and can be the source of a pelvic mass. For instance, exophytic, pedunculated fibroids can mimic adnexal masses on preoperative imaging. The rectum and bladder are located posterior and anterior to the adnexal regions. Both can be the source of pelvic masses, although this is less frequent. In addition, they must be protected from injury when adnexal surgery is performed. The ureters are located near the ovarian blood supply and can be damaged easily during adnexal surgery. Many of the pathologic processes associated with adnexal masses can alter the location of the ureters, increasing the chance of damage.

Contraindications

Many adnexal masses can be removed using laparoscopic techniques and are associated with little postoperative complexity.[29] However, in those women with significant preexisting medical problems and/or cancer, major postoperative problems can be encountered and preoperative evaluation is important to assess clearance for surgery (see Postoperative Details and Complications). In patients with significant medical risk factors for surgery, careful consideration of nonsurgical management and follow-up of low-risk adnexal masses is important to avoid unnecessary procedures and risk to the patient.

Laboratory Studies

Possible lab tests in the evaluation of adnexal mass include serum markers, Papanicolaou test, CBC count, urinalysis (U/A), stool for blood, and electrolytes.

CA-125 is elevated in approximately 80% of all women with ovarian cancer. In stage I disease, the sensitivity of this biomarker is approximately 50%, which rises to 90% in patients with advanced disease.[30] However, it can also be elevated in many other conditions, including gynecologic etiologies such as endometriosis, uterine fibroids, and pregnancy, and nongynecologic conditions such as gastroenteritis, pancreatitis, cirrhosis, and congestive heart failure.[25, 26, 27] As such, the specificity of CA-125 is limited and is not recommended for routine screening purposes in the general population (see Clinical).[31]

Although elevated, levels of serum CA-125 do not appear to be a significant predictor of malignant transformation of endometriosis. Significant predictive factors for the presence of malignant transformation of endometriosis appear to include age older than 49 years and cysts that are multilocular and have solid components.[32]

Several predictive models which combine multiple serum markers with or without ultrasound, such as the Copenhagen Index (CPH-I), Risk of Malignancy Index (RMI), and Risk of Ovarian Malignancy Algorithm (ROMA), and OVA-1 have been developed to differentiate benign from malignant adnexal masses.  In various studies, the sensitivities of these indices for epithelial ovarian cancer range from 53-89% and the specificities range from 67-85%, with the highest sensitivity and specificity in post-menopausal women. The superiority of any one particular algorithm has not yet been demonstrated.[33, 34, 35, 36, 37, 38, 39]

Urine or serum beta human chorionic gonadotropin (ß-hCG) should be obtained in women of reproductive age to rule out pregnancy and pregnancy-related etiologies of adnexal masses.

Other serum markers such as AFP and LDH can be helpful when a germ cell tumor is suspected. An ovarian mass in the setting of a thickened endometrial stripe or abnormal uterine bleeding, inhibin A and B may help with diagnosis of a granulosa cell tumor.

A Papanicolaou test should be considered in women undergoing a gynecologic surgery. This test should be used to help rule out any unknown cervical pathology. In extremely rare situations, this test may reveal the presence of an adnexal malignancy.

A CBC count helps evaluate for presence of inflammation and anemia. An infected mass such as a tubo-ovarian abscess results in an increased WBC count with an associated left shift. Adnexal masses rarely cause anemia, but because they often require surgical removal, this information should be known.

U/A results are generally normal in the presence of an adnexal mass. Bladder pathology may present with symptoms of an adnexal mass and may be discovered based on U/A results. Appendicitis can present similar to an adnexal mass but is often associated with WBCs in the U/A findings.

Results from testing stool for blood should be negative for adnexal masses but may be positive in women with colonic pathology.

Serum electrolytes should not be altered by an adnexal mass; however, symptoms associated with masses, such as nausea and vomiting, can cause alterations that must be known before anesthesia and surgery are considered.

Measuring other hormone levels is generally of limited value in the evaluation of adnexal masses. Obtaining estrogen and progesterone levels may be helpful in women suggested to have functional tumors, such as germ cell tumors, or if a girl younger than 12 years is being evaluated.

Imaging Studies

The most commonly performed test to evaluate an adnexal mass is transabdominal or transvaginal ultrasonography.[6, 7, 8, 40] This test helps demonstrate the presence of the mass and its location (eg, ovarian, uterine, bowel). It also provides the mass size, consistency, and internal architecture. Scoring systems, such as that suggested by DePriest and associates, can then be used to determine the likelihood of a malignant component.[41] Hysterosonography (ultrasonography with the presence of fluid in the uterine cavity) may be used to help distinguish between uterine masses and those arising from other pelvic structures. Color Doppler ultrasonographies can be used to evaluate the resistive index of the mass vessels, which, when low, has been indicative of a malignancy.

Pelvic radiographs are generally not helpful in the evaluation of adnexal masses. A dermoid cyst generally contains areas of calcification that may be picked up on a plain radiograph.

CT scans are most useful for assessing the remainder of the abdomen and pelvis when metastatic disease is suspected. Incidental adnexal masses are sometimes found when CT is performed for evaluation of other conditions. As with ultrasonography, CT scan can help identify the size, location, and relationship to other organs. CT scan is less effective than ultrasonography for determining the internal architecture of these masses.

MRI scans can help characterize adnexal mass characteristics in select cases when ultrasonographic findings are limited.[5]

Diagnostic Procedures

In limited settings, aspiration of the mass can be performed. However, this approach must be reserved for those women in whom an extremely low chance of a malignant mass exists and/or when surgical intervention is contraindicated.

Medical Therapy

Asymptomatic, small, well-characterized adnexal masses may be observed with regular pelvic examinations and radiologic evaluations. A surgical approach should be used if growth occurs in these masses, if the patient becomes symptomatic, or if the cyst develops more concerning features, such as solid components. As indicated previously, the suspicion for a malignancy is increased in prepubescent and postmenopausal women.

Some controversy exists regarding the use of combined hormonal contraceptives in the prevention and treatment of ovarian cysts. Observational studies in women taking higher-dose, “early-generation” oral contraceptive pills (OCPs) suggested a lower incidence of functional and benign epithelial ovarian cysts. However, more recent data have shown that contemporary oral contraceptive formulations have minimal effects on the incidence of ovarian cysts and that treatment with OCPs does not appear to expedite cyst resolution.[42]

Cyst aspiration is contraindicated, especially in postmenopausal patients.  In benign cysts, cyst wall removal is necessary to prevent recurrence and aspiration has little therapeutic benefit.  In malignancy, cytology only has a sensitivity of 25-82% for detection of cancer.  Spillage of cyst fluid may induce peritoneal seeding of malignancy.  Intraoperative cyst rupture is known to decrease overall survival in stage 1 ovarian cancer patients in comparison to intact tumors.  Additionally, there are case reports of recurrence of malignancy along the aspiration needle tract.[1]  

Surgical Therapy

All adnexal masses that are symptomatic or have characteristics of a malignancy should be considered for surgical evaluation. The extensive differential diagnosis and possible surgical procedures should be discussed with the patient.

Obvious benign masses can be treated with resection of the mass alone or removal of the adnexal structure.  In those cases in which the presence of malignancy is questionable, one should limit the resection to the structures involved unless a preoperative decision has been made that a more aggressive approach should be taken.

When an epithelial ovarian malignancy is encountered, a complete staging protocol must be performed. This generally includes complete exploration of the abdomen, hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic and para-aortic lymph node dissections, biopsies of the undersurface of the right and left diaphragms, and biopsies of the colic gutters followed by a maximal resection of the intra-abdominal tumor.[43] In select cases involving women with limited, early stage, low-grade ovarian cancers, a fertility sparing procedure may be considered.[44] In some cases, resecting portions of the small bowel or colon may be necessary; therefore, preoperative bowel preparation may be warranted, as is a discussion about possible colostomy or other bowel changes.

Among women undergoing minimally invasive resection of adnexal masses, a transvaginal approach for specimen removal is associated with less postoperative pain than a transumbilical approach.[45] If a mass has features suspicious for malignancy, care should be made to remove the mass intact.  During minimally invasive surgery, the mass may be placed in a bag prior to morcellation or cyst decompression to avoid potential spread of malignancy.  Intraoperative tumor rupture is significantly more common during minimally invasive removal of adnexal masses as compared to an open approach[46] .

Preoperative Details

Preoperative preparation is vital to the proper care of a woman with an adnexal mass. This should include the following:

Given the limitations of preoperative diagnostic testing in accurately determining the risk of malignancy (see Workup), the American College of Obstetricians and Gynecologists and the Society of Gynecologic Oncologists have established referral guidelines for a newly diagnosed pelvic mass.[1, 47] Women who meet the following criteria would benefit from preoperative consultation with a gynecologic oncologist:

Premenopausal (younger than 50 y)

See the list below:

Postmenopausal (older than 50 y)

See the list below:

Intraoperative Details

During the procedure, several factors must be kept in mind, including the following:

Intraoperative frozen section analysis should be considered based on a number of factors, as follows[48] :

A retrospective analysis of 748 Turkish patients who underwent exploratory laparotomy for adnexal masses found that intraoperative frozen section evaluation was highly accurate in evaluating the tumors when compared to permanent section pathology.[49] However, factors that were associated with misdiagnosis included masses larger than 10 cm and a borderline histology. On the basis of multivariate analysis, borderline history was an independent predicted for misdiagnosis during frozen examination.[49]

Postoperative Details

Most adnexal masses can be removed with relative ease and are associated with little postoperative complexity; however, in women with significant preexisting medical problems and/or cancer, major postoperative problems can be encountered. When indicated, intensive care unit admission with close monitoring of fluid balance, electrolyte balance, coagulation status, and cardiopulmonary function may be required.

Follow-up

Most adnexal masses require little more than the normal annual gynecologic examination for follow-up because they rarely recur. On the other hand, women found to have a malignancy require additional therapy, such as chemotherapy or radiation therapy. Their follow-up care should include frequent reexaminations to determine the disease status.

For patient education resources, see Women's Health Center, as well as Ovarian Cysts.

Complications

The major adverse outcomes in the treatment of adnexal masses are related to complications resulting from surgical therapy. These may include the following:

Outcome and Prognosis

Most adnexal masses are benign; outcome and prognosis are very good. Generally, no impact on life span or quality of life is noted. In fact, most women treated for adnexal masses have no interruption in their reproductive abilities.

Those women who are found to have malignant adnexal masses fall into 3 groups, as follows:

Future and Controversies

Future

The future holds several interesting possibilities. First, the rapid expansion of new laparoscopic equipment, including the robotic surgery platform, makes minimally invasive surgery an area that is gaining increasing importance in the treatment of adnexal masses. Second, the development of new radiologic techniques or expansion of the present techniques will allow the clinician to gain additional characterization of adnexal masses without entering the surgical suite. Third, new molecular, genetic, and biologic markers and therapies should become available that will assist in the diagnosis and treatment of adnexal masses, both benign and malignant.

Controversies

The major controversy surrounding adnexal masses is when and how to treat them. While some adnexal masses can be clearly stratified into low- or high-risk for malignancy based on clinical, laboratory, and clinical findings, currently, there are no definitive means of preoperative diagnosis with imaging or laboratory findings.

Author

Nelson Teng, MD, MS, MBA, PhD, Professor, Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, Stanford University School of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Gillian Lee Hsieh, MD, Fellow in Gynecologic Oncology, Stanford University School of Medicine and University of California, San Francisco, School of Medicine

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

A David Barnes, MD, MPH, PhD, FACOG, Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital (Mammoth Lakes, CA), Pioneer Valley Hospital (Salt Lake City, UT), Warren General Hospital (Warren, PA), and Mountain West Hospital (Tooele, UT)

Disclosure: Nothing to disclose.

Chief Editor

Michel E Rivlin, MD, Former Professor, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Elise J Simons, MD, Clinical Instructor, Department of Obstetrics and Gynecology, Stanford University School of Medicine

Disclosure: Nothing to disclose.

John J Kavanagh, Jr, MD, Chief, Professor, Department of Internal Medicine, Section of Gynecological and Medical Therapeutics, MD Anderson Cancer Center, University of Texas Medical School at Houston

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Margrit Juretzka, MD, to the development and writing of this article.

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