Management of the Adnexal Mass
Uterine adnexae are defined as the areas adjacent to the uterus that are occupied by the fallopian tubes and ovaries. The embryologic origin of the fallopian tubes and ovaries are 2 distinct events in the development of a female embryo. Development of the ovaries begins before the development of the remainder of the genital tract. The origin of the male and female gonads are similar up until the seventh week of gestation, at which time the primitive sex cords begin to break up in the female embryo. The developing ovary eventually has 3 layers: the surface epithelium, primitive germ cells, and sex cord epithelium. These layers give rise to the 3 main types of ovarian tumors: (1) epithelial tumors, which comprise approximately 70% of all ovarian neoplasms; (2) germ cell tumors, which comprise 15% to 20% of ovarian tumors; and (3) sex cord–stromal tumors, which account for 5% to 10% of ovarian tumors. The remainder of the masses are a result of metastatic or secondary involvement to the ovary.1
It is estimated that 289,000 women will undergo surgical intervention for an adnexal mass in the United States every year.2 This represents one of the most common indications for gynecologic surgery.3 The determination of whether a mass represents a condition that requires immediate surgical intervention, or is likely to be malignant or benign, is of paramount importance. A patient’s demographics, presenting symptoms, physical examination, imaging, laboratory studies, and family history can provide invaluable insights in determining the appropriate treatment plan. Given this information, a physician can form an accurate differential diagnosis and establish an appropriate management plan.
DIAGNOSIS
Key Points
1. Ultrasound characteristics of malignant adnexal masses include presence of complex or solid components, presence of ascites, bilaterality, and size greater than 10 cm.
2. Serum tumor markers useful in the evaluation of adnexal masses include CA125, alpha-fetoprotein, lactate dehydrogenase, human chorionic gonadotropin, and inhibin A and B.
3. Novel markers, including human epididymis 4 protein (HE4), transthyretin, transferrin, β-microglobulin, and apolipoprotein A1 may improve preoperative assessment of the risk of malignancy in adnexal masses.
Symptoms
Not all patients with an adnexal mass initially present with symptoms. Some masses are found incidentally on imaging ordered for the evaluation of unrelated conditions. However, when patients do present with symptoms, detailed evaluation and characterization of the reporting signs can provide insight into the etiology of the mass. Physicians should question patients regarding the duration, intensity, location, and radiation of their pain to determine whether immediate surgical intervention is needed for conditions such as ovarian torsion or ectopic pregnancy. Physicians should also perform a complete review of systems focusing on symptoms that can help elucidate the etiology of an adnexal mass such as the following: fevers, chills, vaginal discharge, vaginal bleeding, weight loss, abdominal bloating, changes in bowel or bladder function, and early satiety.4
Abdominal pain is a common presenting symptom for the majority of patients who are diagnosed with an adnexal mass. The first step in treating a patient who presents with abdominal pain is to differentiate those who will ultimately be diagnosed with conditions that require emergent surgical intervention, such as ectopic pregnancy, adnexal torsion, or a ruptured tubo-ovarian abscess (TOA). A pregnancy test should be performed in any woman of reproductive age whose symptoms include abdominal pain and abnormal bleeding. In the case of a ruptured TOA, a patient may have signs and symptoms of an acute abdomen and/or hemodynamic instability, requiring emergent surgical intervention.5 Similarly, adnexal torsion may be an operative emergency. Torsion is defined as the twisting of an ovarian mass around the infundibulo-pelvic ligament, which results in compromise of the arterial and venous blood flow. This is a condition that is often difficult to diagnose and requires a high suspicion from the patient’s initial presentation. Findings consistent with adnexal torsion include acute onset of abdominal pain (< 8 hours), vomiting, and absence of bleeding or leukorrhea. Thus, particularly in premenopausal women, prompt recognition and treatment is paramount in preserving the involved ovary.6 Another entity that commonly presents with abdominal pain, a pelvic mass, and fever is a TOA. Leukorrhea combined with a previous diagnosis of pelvic inflammatory disease (PID) or sexually transmitted infection should also raise the suspicion of TOA, as 30% of patients admitted with PID will go on to develop a TOA.7
Once emergent situations are excluded, the focus of the evaluation of an adnexal mass turns to determination of its etiology. A patient’s presenting symptoms may initially help determine the likelihood that a mass is malignant. In 2000, Goff et al8 evaluated the symptoms of 1725 women with ovarian cancer and found that 95% had previously presented with symptoms before their diagnosis. The most commonly reported symptoms were related to abdominal and gastrointestinal complaints. They also found that 89% of patients with stage I/II disease had symptomatic complaints before their diagnosis. In supplementary studies, further characterization of symptoms most indicative of malignancy, accounting for duration, intensity, and frequency, was conducted. The Early Ovarian Cancer Detection Study, which comprised a 23-item symptom index in an exploratory group of patients, found that the symptoms that strongly correlated with an ultimate diagnosis of ovarian cancer were pelvic pain, abdominal pain, increased abdominal size or bloating, early satiety, and difficulty eating. Further assessment of a modified symptom index in women with at least 1 symptom for less than a year and occurring greater than 12 times per month had an accuracy of 56.7% in women with early-stage ovarian cancer and in 79.5% in women with advanced-stage disease.9
In addition to the symptoms discussed in the preceding paragraph, other presenting complaints, when combined with the finding of an adnexal mass, may point to less common types of ovarian neoplasms. Estrogen-secreting tumors, such as granulosa cell tumors or a thecomas, should be considered in women with an adnexal mass, abnormal uterine bleeding, and breast tenderness, or precocious puberty in prepubertal females.10–12 In contrast, Sertoli-Leydig tumors, which secrete testosterone, often present with symptoms such as hirsutism and deepening of the voice.13 Other rare findings may include symptoms of hyperthyroidism in patients with a struma ovarii or symptoms such as flushing, diarrhea, and palpitations in women with a carcinoid tumor of the ovary.
Physical Examination
A thorough physical examination is advocated for the assessment of an adnexal mass, whether detected incidentally in an asymptomatic patient, or for the evaluation of symptoms. The health care provider should note general appearance. This includes assessment for signs of cachexia, such as temporal wasting, which may be found in women with advanced malignancies. Patients with a functional tumor may have signs of virilization, including hirsutism, male pattern balding, clitoromegaly, and acne indicating a hyperandrogenic state, or breast tenderness and vaginal bleeding, possibly suggesting a hyperestrogenic state.
In addition to a general examination, emphasis should be placed on a comprehensive evaluation of supra clavicular, axillary, and inguinal lymph nodes. Abdominal examination is a critical portion of the physical examination, allowing for palpation of large masses and assessment of pain. Tenderness, particularly with fever, may indicate an infectious process, such as a TOA. Presence of a fluid wave or omental caking may be indicative of advanced ovarian cancer.4,14
The pelvic examination affords assessment of the uterus and the adnexae. Speculum examination provides evaluation for signs of recent bleeding or displacement of the cervix secondary to the presence of a pelvic mass. Furthermore, characteristics of the mass, such as contour (smooth vs. irregular), firmness (solid, cystic, or mixed), and mobility should be assessed on examination. The rectovaginal examination allows for palpation of the uterosacral ligaments and the culde-sac, where nodularity or obliteration may suggest the presence of endometriosis or metastatic cancer. If a primary colonic malignancy is suspected, a stool guaiac should be performed.4
Studies have shown that examiners, regardless of experience, tend to underestimate the size of a mass on pelvic examination.15 In a pooled analysis of studies evaluating the ability of pelvic examination to detect a pelvic mass, sensitivity was 45%.14 Therefore, one must recognize the limitations of the pelvic examination, which can be further compromised by the presence of a small adnexal mass or in the obese patient.14,15 Thus a normal examination does not eliminate the need for further evaluation.
Radiographic Imaging
Once an adnexal mass is suspected, the proper imaging modality must be determined. Ultrasound uses high-frequency ultrasonic waves to create a picture of the internal and external structures of a mass (Figure 11-1). Used either transvaginally and/or transabdominally, it is both an inexpensive and accurate way to determine the origin of an adnexal mass and allows further characterization of the mass as benign, malignant, or indeterminate.16 Table 11-1 provides an overview of common characteristic appearances on ultrasound for benign and malignant ovarian masses.17
Table 11-1 Ultrasound Characteristics for Common Adnexal Masses
FIGURE 11-1. A simple ovarian cyst on transvaginal ultrasound.
In 2009, Sokalska et al18 studied the ability of ultrasound to provide a specific diagnosis of an adnexal mass that was compared with final pathology after surgical management. In 800 women with benign processes, the sensitivity of diagnosing dermoid cysts (86%), hydrosalpinges (86%), and endometriomas (77%) were the highest among all ovarian pathologies. In addition to the detection of benign conditions, certain ultrasound findings can also raise the suspicion of a malignant origin. The size, location, locularity, echogenicity, and blood flow of a mass are characteristics used to determine the malignant potential of a pelvic mass. In an evaluation of symptoms in combination with ultrasound findings, the factors that raised the probability of malignancy were a personal history of ovarian cancer, older age, presence of ascites, presence of blood flow within a solid papillary projection, increasing diameter of the solid component of the mass, and irregular internal cyst walls. Factors that decreased the probability of malignancy were the presence of pain during the ultrasound examination, current use of hormonal therapy, and the presence of acoustic shadows. The ultimate sensitivity and specificity of this model were 93% and 76%, respectively.19 McDonald et al20 also looked at ultrasound characteristics of adnexal masses that conferred a probability of malignancy. This study confirmed that older age (> 55 years), presence of complex or solid components, presence of ascites, bilateral tumors, and a mass greater than 10 cm were all associated with an increased risk of malignancy at the time of surgical intervention.
The use of color flow Doppler, which evaluates the blood flow of a mass, has also been studied for the evaluation of an adnexal mass. However, this technique has been found to be inconsistent in the differentiation between various etiologies and not recommended for routine use at this time.17 The introduction of 3-dimensional (3D) ultrasound and its utility in the evaluation of a pelvic mass has been less clearly defined. Recent studies have compared the use of 3D ultrasound with conventional ultrasound for the evaluation of a pelvic mass. However, results are premature, and given the limited data, high costs, and availability of 3D ultrasound, its routine use for evaluation of an adnexal mass is not yet recommended.21
Though not ideal for initial imaging, the use of magnetic resonance imaging (MRI) may be helpful in further assessing those masses that have an indeterminate malignant potential on ultrasound. The differential diagnosis of an indeterminate adnexal mass on MRI is determined by its dominant signal characteristic. Mature teratomas, hemorrhagic cysts, endometriomas, mucinous cystadenomas, and melanoma metastasis are characterized by a “bright” T1 signal. The T1 signal helps to further define components of blood, blood clots, fat, and proteinaceous material that suggest a benign lesion, but are not always clearly delineated with ultrasonography. These images are especially helpful in defining heme-filled masses that may appear to be solid in nature on ultrasound. In addition, fat-suppressed T1 images are used to identify small amounts of fat within an adnexal mass that most often signify a mature teratoma.22 In contrast to this, lesions demonstrating a solid T2 signal may be either malignant or benign. Masses that are homogenously dark, well circumscribed, and smooth are most often leiomyomas or an ovarian fibroma/thecoma. A mixed signal solid mass on T2 imaging should raise an increased suspicion of malignancy. These are usually demonstrated by tumors that express both dark and bright signals. Lastly, tumors that have a predominantly cystic-solid appearance may be aided by further evaluation by MRI. Multilocular benign ovarian cysts, hydrosalpinx, and cystadenomas may appear to have “pseudo-solid” areas on ultrasound that are truly opposed folds of an otherwise cystic mass and that are able to be delineated by MRI. Further characterization of solid-cystic masses can be performed using contrast-enhanced MRI. The addition of contrast helps to more accurately identify solid components, such as mural nodules, areas of necrosis, and vegetations, which are concerning for malignancy.16,22 Although MRI is expensive, its use to determine the appropriate therapeutic modality in patients with an indeterminate adnexal mass may be warranted. Because the majority of these masses will ultimately be benign in nature, the cost of an MRI may be indicated, as it may prevent patients from undergoing an unnecessary surgical procedure.22
In past decades, the use of computed tomography (CT) has been reserved for pre- and postoperative treatment planning for patients with ovarian cancer and not for detailed characterization of adnexal masses. This was mostly secondary to the inadequate characterization of soft tissue densities and the added exposure to radiation.23 In 1998, the introduction of sub-millimeter spatial resolution and 2- and 3D spatial reconstruction resulted in the ability of CT scans to provide more accurate staging, evaluate disease volume, and determine resectability of metastatic ovarian cancer. In 2008, Tsili et al23 conducted a prospective study that evaluated the use of CT in the detection and characterization of adnexal masses in patients diagnosed with an adnexal mass on physical exam or ultrasound. Characteristics examined on preoperative CT that were thought to be consistent with a malignant process included a diameter greater than 4 cm, presence of bilateral ovarian masses, cystic and solid components, necrosis present within a solid lesion, and a cystic lesion that contained thick (> 3 mm) or irregular walls, septa, or papillary projections, as well as extra-ovarian disease (Figure 11-2). CT scanning correctly identified the origin of the adnexal mass in 96% of patients, with an overall diagnostic accuracy of 89%,23 thus concluding that CT scans can provide an accurate characterization of adnexal masses.
FIGURE 11-2. Large mucinous cystadenoma with multi-loculations (depicted by arrows) on CT scan.
The preferred imaging strategy of an adnexal mass is to start with the least expensive and readily available test, which, in most cases, is an ultrasound. For masses that are highly suspicious for malignancy on ultrasound, use of a CT scan may be considered for preoperative staging and determination of disease resectability. If a mass is indeterminate on ultrasound, either an MRI or CT may be used for further evaluation; however, the diagnostic test chosen should take into consideration the availability of resources, costs to the patient, and the implications of radiation exposure.
Tumor Markers
The use of tumor markers may aid in determining the malignant potential and histology of an adnexal mass. Typically elevated in patients who are ultimately diagnosed with cancer, the utility of tumor markers may be helpful in the initial diagnosis, monitoring of response to treatment, and triaging to the appropriate specialist. However, tumor markers should be ordered selectively, and physicians should take into account the patient’s age, presentation of symptoms, findings on physical examination, and imaging.
Though currently there are no validated biomarkers for ovarian cancer screening, the use of CA-125 level has been extensively studied. CA-125 is a glycoprotein that is produced by the ovary, peritoneal, and pleural linings. Although it is frequently elevated in malignant conditions, it can also be increased with benign processes, such as endometriosis and PID. In contrast, patients with early-stage epithelial ovarian carcinoma or borderline tumors may present with a normal CA-125 value.24 However, when assessing a patient’s risk of malignancy, this value may contribute to management decisions.
Germ cell tumors are most commonly associated with secretion of tumor markers. α-Fetoprotein (AFP) is an oncofetal protein that was initially characterized in the fetal liver and yolk sac, and elevation of this protein is often seen in hepatocellular carcinoma, gastric cancer, colon cancer, and pancreatic cancer.25 Because the fetal liver and yolk sac produce AFP, tumors that resemble these tissues are often associated with increased serum levels. Kawai et al26 examined at the association of 7 tumor markers with malignant germ cell tumors of the ovary. One hundred percent of patients with endodermal sinus tumors, 61.9% of patients with immature teratomas, and 11.8% of patients with dysgerminomas had elevated serum levels of AFP. More commonly, dysgerminomas, and to a lesser degree other germ cell tumors, are associated with an elevation in lactate dehydrogenase (LDH). Another commonly expressed tumor marker in germ cell tumors is human chorionic gonadotropin (hCG). This glycoprotein hormone, which is produced in pregnancy, is also secreted by germ cell tumors such as choriocarcinoma, embryonal carcinoma, and dysgerminoma (low levels).26,27
Inhibin A and B, which belong to heterodimeric glycoproteins of the transforming growth factor β family of growth factors, are the most common tumor markers associated with sex cord–stromal tumors, specifically granulosa cell tumors. In 2007, Mom et al28 looked at the prevalence of elevations in both inhibin A and B in patients diagnosed with granulosa cell tumors. They found that 89% of patients had an elevated inhibin B level at the time of diagnosis, but only 67% had elevations in inhibin A. More patients were also noted to have an increase in inhibin B at the time of recurrence when compared with inhibin A. The conclusion from this study was that inhibin B levels more accurately reflect disease status in patients with granulosa cell tumors than inhibin A and should be used for diagnosis and monitoring.
Other biomarkers have also been evaluated in the work-up of a pelvic mass. CA 19-9, a monosialoganglioside, is commonly used for mucinous tumors of the gastrointestinal tract, most notably of the pancreas and biliary tract; however, it has also been found to be associated with mucinous tumors of the ovary. Unfortunately, CA 19-9 has not been helpful in separating benign from malignant tumors and is not recommended for use in triaging patients.29 Another marker is carcinoembryonic antigen (CEA), which is an oncofetal antigen most often found in the colon. In the evaluation of an adnexal mass, CEA has limited potential; however, it may be useful for detection of a colonic primary or metastatic disease involving the adnexa.30
The routine use of tumor markers in the evaluation of an adnexal mass can be helpful in determining the risk of malignancy, and therefore, the need for surgical intervention or referral. Table 11-2 lists the recommended tumor markers in the initial evaluation of an adnexal mass based on age at presentation. Caution should be used in placing a high degree of emphasis on the results of these laboratory values, and the entire clinical picture should be evaluated when determining a patient’s ultimate treatment plan.
Table 11-2 Tumor Marker Recommendations Based on Age
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