Adnexal mass: Ultrasound categorization

INTRODUCTION — An adnexal mass (mass of the ovary, fallopian tube, or surrounding connective tissues) is a common gynecologic issue and may present with pelvic pain or pressure or be an incidental finding on pelvic examination or pelvic imaging.

Pelvic ultrasound is typically the first-line imaging study used to characterize an adnexal mass. A sonologist must employ various sonographic techniques and incorporate the patient's relevant clinical information to assist in the sonographic characterization of the mass and differentiate between normal physiology and a pathologic process.

Sonographic findings are then used to classify the adnexal mass into specific categories, each with a defined risk of malignancy (ROM). Characterization of the mass into the appropriate category is of paramount importance since clinical management of the mass will greatly depend on this categorization.

This topic will discuss the ultrasound characterization of adnexal masses. The various types of adnexal masses, clinical approach to evaluation, and management of a patient with an adnexal mass are reviewed in detail separately:

●(See "Adnexal mass: Differential diagnosis".)

●(See "Approach to the patient with an adnexal mass".)

ETIOLOGY OF ADNEXAL MASSES — Anatomically, most adnexal masses arise from the ovary or fallopian tube; other gynecologic structures that may give rise to an adnexal mass include the mesovarium or mesosalpinx (eg, paratubal cysts). Nongynecologic masses arising from proximal structures may be palpated or visualized as an adnexal mass; masses may originate from the uterus (leiomyomas), urinary tract (bladder diverticulum), bowel (appendiceal abscess, diverticular abscess, bowel neoplasm), pelvic connective tissue (peritoneal cyst), and nerves (nerve sheath tumor). The various types of adnexal masses are shown in the table (table 1). (See "Adnexal mass: Differential diagnosis".)

Adnexal masses may be physiologic (a normal component of ovulation) or pathologic. Normal ovulatory physiology is the most common cause of an adnexal mass in a premenopausal patient. Thus, an understanding of normal menstrual cycle physiology and the ability to sonographically identify features consistent with a physiologic adnexal mass (image 1 and image 2) are critical to classifying a mass as "almost certainly benign" (table 2). (See 'Overview' below and "Ultrasound evaluation of the normal menstrual cycle", section on 'Ovarian changes during the normal menstrual cycle'.)

Nonpathologic ovarian cysts are also routinely found in postmenopausal patients; they are not exclusively a premenopausal phenomenon as previously considered [1]. In many cases, these cysts represent arrested physiologic follicles from an anovulatory cycle, but they can also be due to sporadic ovulation [2] or represent small cystadenomas. Physiologic follicles from sporadic ovulation become less common and smaller with increasing time from the final menstrual period.

CLINICAL FEATURES RELEVANT TO ULTRASOUND INTERPRETATION — Patient's age, family history, and menopausal status are important for predicting cancer risk, since malignancy is more common in postmenopausal patients and those with certain heritable conditions (table 3). (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Incidence and risk factors", section on 'Probable risk factors'.)

Other clinical information (eg, fever, leukocytosis, pregnancy, pelvic pain, symptoms of ovarian cancer (table 4)) may also be critical in the sonographic evaluation of adnexal masses.

SONOGRAPHIC ASSESSMENT

Overview — The goal of ultrasound evaluation of the adnexal mass is not, strictly speaking, to determine if the mass is "definitely" benign versus "definitely" malignant. Instead, the goal is to determine whether the mass is "almost certainly benign" or whether the mass has some "reasonable chance of being malignant."

The asymmetry in these categories with respect to specificity is purposeful. The adnexal mass that is "almost certainly benign" should have practically no risk for malignancy (very high specificity). Thus, it should be reasonable not to proceed with surgical intervention in these cases. Some of these masses may require surgical intervention or imaging follow-up for reasons other than excluding malignancy (eg, pain, torsion). On the other hand, some adnexal masses that ultrasound characterizes as having "a reasonable chance of being malignant" may prove to be benign (higher sensitivity but lower specificity), but these masses require further diagnostic testing or surgical intervention because the goal is to detect nearly all malignant masses. Proper categorization of the level of risk in these patients, using standardized categorization, allows the clinical provider to pursue the best management strategy. (See 'Classification systems' below.)

Primary techniques — Most adnexal masses can be characterized using pelvic gray-scale sonography with addition of color Doppler evaluation.

The basic principle of ultrasound imaging is that ultrasound waves are delivered into the body from the crystal surface of a hand-held transducer, which then also records the waves that are reflected back to the crystal ("echoes") from internal structures and interfaces.

Gray-scale — Gray-scale ultrasound imaging refers to the technique in which the reflected ultrasound wave is displayed on the image as a pixel of a particular shade of gray based on the signal intensity, with the depth of the pixel on the image based on the time it took for the reflected wave to return to the crystal. This results in a two-dimensional display of anatomy.

Doppler — Doppler evaluation refers to the change in frequency that results from sound waves that reflect off of moving particles, such as blood flow. In ultrasound imaging, those Doppler changes can be displayed using color maps (known as color Doppler) or as a waveform showing the change in frequency as a function of time (known as spectral Doppler).

Using color Doppler evaluation during pelvic ultrasound is a routine maneuver that is usually considered part of a standard evaluation and not an additional test. In particular, for adnexal masses that do not have a typical benign appearance, using color or power Doppler to look for the presence or absence of flow in solid-appearing areas or septations is important (image 3 and image 4) [3]. Within a cyst, Doppler evaluation helps to distinguish clot (avascular, related to non-neoplastic physiologic etiology) from a mural nodule (vascularized and a feature suspicious for malignancy); artifactual flow may occur as a result of movement of a cyst with the transducer during the examination.

Combined gray-scale and Doppler evaluation — Meta-analyses of observational studies have shown that combined evaluation of ovarian masses with gray-scale morphology and color Doppler assessment performs better than morphologic assessment, pulsed Doppler assessment, or color Doppler assessment alone [4,5].

Combined evaluation can be performed with the use of a scoring system, in which numerical values are assigned to different features and a total score for the mass or a probability of malignancy can be calculated. In daily practice, however, many experienced sonologists will use the features that individual studies have identified as most valuable to arrive at a subjective impression of the likelihood of malignancy [6-9]. Using gray-scale and color Doppler features is a subjective approach that has been shown to be highly reliable and usually superior to other methods [10-12]. (See 'Malignancy' below.)

Techniques not typically used

●Three-dimensional techniques – Adding three-dimensional color techniques has not shown any improvement in the ability to differentiate benign from malignant lesions [3]. However, three-dimensional gray-scale imaging can be helpful to make a specific diagnosis of hydrosalpinx [13].

●Spectral Doppler – Ultrasound with spectral Doppler evaluation for adnexal masses was initially proposed as a means of decreasing the false-positive rate of sonography for ovarian carcinoma [14]. The neovascularization that accompanies malignant tumors is associated with poor muscular support in the arterial walls, leading to less vascular resistance that potentially can be detected by pulsed Doppler. However, spectral Doppler does not appear to be useful in diagnosing ovarian malignancy, as many studies have found too broad an overlap in resistive index and pulsatility index between benign and malignant masses.

Other spectral Doppler features, such as velocity criteria or the presence or absence of a diastolic notch in the pulsed Doppler waveform, have been investigated and are generally not found to be reliable for differentiating benign and malignant masses [6,15,16], although some believe them to be useful [17].

Diagnostic performance — Pelvic ultrasound is highly effective at determining which masses are "almost certainly benign" and which have a "reasonable chance of malignancy" [18], but studies show that the diagnostic performance of ultrasound is highly dependent on both the quality of the ultrasound examination and the interpretation of the ultrasound findings [19,20].

The largest diagnostic accuracy study regarding sonographic differentiation of benign and malignant adnexal masses was the International Ovarian Tumor Analysis (IOTA) study, an international multicenter prospective study that evaluated the use of a set of sonographic features (the "Simple Rules") in almost 5000 patients with adnexal masses [21,22]. The IOTA data show that the performance of ultrasound depends on which level of "risk of malignancy" (ROM) one is willing to accept for patients who are deemed not to have a malignancy based on any algorithm using sonographic features.

For example, if one pursues a strategy in which an adnexal mass that is deemed not to be malignant based on certain sonographic findings has only 1 percent risk of being malignant (high sensitivity/low specificity), then ultrasound shows 99.7 percent sensitivity, 33.7 percent specificity, positive predictive value (PPV) of 44.8 percent, and negative predictive value (NPV) of 98.9 percent. Alternatively, if one pursues a strategy in which an adnexal mass deemed not to be malignant based on certain sonographic findings has 30 percent ROM, ultrasound sensitivity was 89.0 percent, specificity 84.7, PPV 75.4, and NPV 93.9 percent.

In a meta-analysis comparing the ability of 19 various methods to discriminate between benign and malignant adnexal masses before surgery, the Simple Rules method had a sensitivity of 93 percent and a specificity of 81 percent when inconclusive tumors were all considered malignant [18]. The Simple Rules are described in detail below. (See 'IOTA Simple Rules' below.)

CLASSIFICATION SYSTEMS — There is no universally accepted classification system for adnexal masses; use of the various systems typically varies by setting, provider practice patterns, and reimbursement requirements. This topic will primarily utilize the Ovarian-Adnexal Reporting and Data System (O-RADS); however, the International Ovarian Tumor Analysis (IOTA) Simple Rules are also widely used.

IOTA Simple Rules — One approach to determining the likelihood of malignancy in an adnexal mass on ultrasound is described by the International Ovarian Tumor Analysis (IOTA) study group and has been termed the "Simple Rules" (see 'Diagnostic performance' above). This is based on a set of five ultrasound features indicative of a benign tumor (B-features) and five ultrasound features indicative of a malignant tumor (M-features) (image 5) [22]:

●B-features – (1) Unilocular cyst, any size; (2) solid components either not present or less than 7 mm in diameter; (3) presence of acoustic shadowing; (4) smooth multilocular cyst less than 10 cm in diameter; and (5) no blood flow.

●M-features – (1) Irregular solid tumor; (2) ascites; (3) at least four papillary structures; (4) irregular solid-multilocular tumor, largest diameter over 10 cm; and (5) very strong color flow.

When using the Simple Rules, tumors are classified as benign if only B-features are observed and as malignant if only M-features are observed. If no features are observed, or if conflicting features are present, the Simple Rules are deemed unable to classify the tumor as benign or malignant (inconclusive results).

While many adnexal masses can be "instantly" classified based on characteristics features (eg, endometrioma, cystic teratoma, simple cyst/cystadenoma, malignancy), some cannot. For such masses, one diagnostic strategy (the "two-step strategy") is to combine the "instant" diagnosis with the Simple Rules to help obtain a diagnosis; a "three-step strategy," when an expert sonologist further assesses a mass that is not otherwise classified by the "two-step strategy," may also be used [23]. In one prospective external validation study, the "two-step strategy" had a sensitivity and specificity for ovarian malignancy of 98 and 64 percent, respectively; when the "three-step strategy" was applied, the sensitivity and specificity was 95 and 98 percent, respectively [24]. In a subsequent retrospective study, a variation of this approach classified 970 lesions as "classic" (ie, simple cyst, hemorrhagic cyst, endometrioma, dermoid) or "nonclassic" (ie, other lesions); the overall malignancy rate was 6 percent [25]. The malignancy rate for "classic" compared with "nonclassic" lesions was <1 and 32 percent, respectively.

O-RADS — The American College of Radiology (ACR) formed the Ovarian-Adnexal Reporting and Data System (O-RADS) committee to develop a risk stratification and management system to assist those who interpret pelvic ultrasound examinations by providing a framework for rendering consistent interpretations that avoid ambiguity in assessment of malignancy risk [26,27]. Using the O-RADS ultrasound classification system, an adnexal finding that has been adequately evaluated sonographically is placed into one of five malignancy-risk categories based on relevant sonographic features, described using specified terms. The 2022 O-RADS ultrasound assessment categories and malignancy risk estimates are available online and include the following:

●Normal ovary (O-RADS 1)

●Almost certainly benign (O-RADS 2; <1 percent risk of malignancy [ROM])

●Low risk of malignancy (O-RADS 3; 1 to <10 percent ROM)

●Intermediate risk of malignancy (O-RADS 4; 10 to <50 percent ROM)

●High risk of malignancy (O-RADS 5; ≥50 percent ROM)

While the O-RADS system is new in 2020, it is founded on years of data established by IOTA and other studies, and appears to compare favorably with other established classification systems:

●In a meta-analysis evaluating the diagnostic performance of O-RADS in patients with an ovarian or adnexal lesion, O-RADS ultrasound compared with IOTA had similar sensitivity and specificity (93 to 96 percent and 76 to 82 percent, respectively; four studies) [28]. Similarly, in a cohort study in the United States including 511 patients with adnexal lesions, O-RADS, IOTA, and the Assessment of Different Neoplasias in the Adnexa (ADNEX) model performed similarly in differentiating between benign and malignant lesions [29]. The ADNEX model is described separately. (See "Adnexal mass: Role of serum biomarkers in diagnosing epithelial carcinoma of the ovary, fallopian tube, or peritoneum", section on 'ADNEX model'.)

●Studies assessing the diagnostic performance of O-RADS show that the system demonstrates excellent sensitivity in classifying malignancies into intermediate (O-RADS 4) and high (O-RADS 5) risk categories [30-32]. In one retrospective study in the above meta-analysis including 304 malignant masses, 300 were categorized as O-RADS 4 or O-RADS 5 (98.6 percent sensitivity, 95% CI 0.96-0.99); only 2 of 182 (1 percent) masses categorized as O-RADS 3 and 2 of 446 masses (<1 percent) categorized as O-RADS 4 were malignant (all borderline tumors), consistent with the expected ROM for those categories [30].

Therefore, in the context of the stated goal of sonographic assessment, observations that result in O-RADS 1 and 2 categorizations can be considered "almost certainly benign," justifying little or no subsequent imaging in the absence of compelling clinical considerations (eg, large size [>10 cm]), while O-RADS 4 and 5 masses have a "reasonable chance of malignancy" and justify additional imaging or surgical intervention.

In general, O-RADS 3 masses benefit from further evaluation by an ultrasound specialist or with magnetic resonance imaging (MRI) to ensure the mass has not been underscored (ie, truly O-RADS 4 or 5 but mistakenly considered O-RADS 3) or overscored (truly O-RADS 1 or 2 but mistakenly considered O-RADS 3), but ultimately depends on the experience and diagnostic confidence of the imager; subsequent management is highly influenced by clinical setting and provider and patient preferences. (See 'Step four: Is additional evaluation needed?' below and "Approach to the patient with an adnexal mass".)

STEPS IN CHARACTERIZING A MASS — Once a set of adnexal observations is considered beyond those that can be summarily dismissed as part of the normal ovary (see 'Etiology of adnexal masses' above), the sonographic approach to adnexal mass characterization can be summarized as a four-step approach:

Step one: Is it a simple cyst? — The first observation that helps to characterize a mass is to determine whether it appears to be a simple cyst. Simple cysts are characterized by:

●Round or oval shape

●Anechoic fluid filling the cyst cavity

●Thin walls

●No impairment of sound transmission through the mass (in other words, no loss of signal from tissues behind the cyst)

●No internal flow with color Doppler imaging

In premenopausal patients, simple adnexal cysts ≤3 cm in diameter typically represent normal follicles or a corpus luteal cyst and may be considered a normal finding (Ovarian-Adnexal Reporting and Data System [O-RADS] 1). (See 'O-RADS' above.)

In pre- and postmenopausal patients, simple cysts >3 but <10 cm in diameter are classified as "almost certainly benign" (O-RADS 2) (see 'O-RADS' above). Higher thresholds for defining a simple cyst as benign have been described [33,34].

There is accumulating evidence that simple cysts are not associated with an increased risk of malignancy (ROM) in pre- or postmenopausal patients [35-37]. The ROM in a simple cyst in a postmenopausal patient is discussed in detail separately. (See "Approach to the patient with an adnexal mass", section on 'Management according to mass type'.)

Other masses that may appear as simple cysts include the following:

●A cystadenoma is a benign neoplasm that usually arises from the ovary but sometimes from the fallopian tube or a paratubal cyst. A cystadenoma should be considered as a possible etiology if there is a persistent, relatively large, simple cyst (>5 cm in diameter in premenopausal patients or >3 cm in diameter in postmenopausal patients). (See "Adnexal mass: Differential diagnosis", section on 'Serous or mucinous cystadenoma'.)

●Paraovarian or paratubal cysts are common and generally appear as simple cysts adjacent to the ovary (image 6). (See "Adnexal mass: Differential diagnosis", section on 'Paraovarian/paratubal cysts and tubal and broad ligament neoplasms'.)

Step two: Are findings consistent with another physiologic process? — If the mass is not a simple cyst, the next question to consider is whether a physiologic process, such as corpus luteal involution, hemorrhage into a cyst, or adjoining simple cysts, could account for the sonographic features that make the cyst "not simple" [38].

Potentially confusing features that may be present in a cyst caused by physiologic processes include:

●Corpus luteum – The corpus luteum has a characteristic appearance to experienced sonographers, with thickened walls, circumferential color Doppler flow, and a small central lucency containing echoes that can be confusing to less-experienced imagers (image 7).

●Two simple cysts – Two simple cysts next to each other can simulate a septated single cyst (image 8).

●Hemorrhagic cyst – Hemorrhage into a cyst, which usually indicates a physiologic cyst, can simulate septations and mural nodules. A fine network of thin linear to curvilinear echoes, sometimes called a fishnet or reticular pattern, is strongly suggestive of a hemorrhagic cyst (image 2) [39]. These linear echoes are usually very thin and do not extend completely uninterrupted across the cyst, unlike true septa.

Step three: Are findings consistent with a specific pathologic process? — If the adnexal mass does not have recognizable features of a simple or physiologic cyst (see 'Step one: Is it a simple cyst?' above and 'Step two: Are findings consistent with another physiologic process?' above), the next task for the sonologist is to critically evaluate the mass for any features that are characteristic of specific pathologic entities, including:

Endometrioma — An endometrioma is a benign cause of an ovarian mass arising from the growth of ectopic endometrial tissue and is a finding in some patients with endometriosis. Classic sonographic characteristics of an endometrioma include:

●Homogeneous (eg, ground glass) low- to medium-level echoes in a cystic mass (whether unilocular or multilocular), in the absence of a solid component (image 9 and image 3) [40-42]

●Small echogenic foci on the inner wall of the cyst [40]

●Varying degrees of echogenicity in the different locules

When an adnexal mass has characteristic features of an endometrioma, it is considered a "classic benign lesion" (O-RADS 2) (see 'O-RADS' above). However, not all endometriomas have the typical appearance described here [40] and some endometriomas have characteristics that overlap with other diagnoses (eg, hemorrhagic cysts, malignancy). An ultrasound report in which the sonologist gives the likely diagnosis of an endometrioma is best reserved for cases in which all the typical features are identified and at least one sonographic follow-up study has been performed [40].

Up to 25 percent of endometriomas will have a solid-appearing nodular component (due to clot or to focal endometrial tissue) that may be difficult to distinguish from true solid tissue of a neoplasm [43,44]. This was best illustrated in the International Ovarian Tumor Analysis (IOTA) studies (see 'Diagnostic performance' above), which included over 700 patients with histologically proven endometriomas [45]. Features of these masses, including a unilocular cyst (51 percent), cyst fluid with ground-glass echogenicity (73 percent), solid parts (17 percent), and/or papillary projections (10 percent), were also found in malignant masses. Among masses with ground-glass appearance on imaging, endometriomas were diagnosed on histopathology in 83 and 16 percent of pre- and postmenopausal patients, respectively, while malignancy was diagnosed in 4 and 44 percent of pre- and postmenopausal patients, respectively. Solid parts were visualized in 17 percent of endometriomas and 93 percent of malignant tumors. Based on subjective impression, 5 of 26 (19 percent) postmenopausal patients presumed to have an endometrioma were eventually diagnosed with a malignant tumor.

While a clot, unlike a solid mass, generally does not exhibit detectable blood flow (image 2), color Doppler has not been shown to be particularly useful in differentiating endometriomas from malignancy. This may be because endometrial tissue in endometriomas may have detectable flow by color Doppler imaging (ie, a vascularized nodule) which simulates malignancy.

The management of an endometrioma is discussed elsewhere. (See "Endometriosis: Management of ovarian endometriomas".)

Mature teratoma — Mature cystic teratomas (dermoid cysts) are benign germ cell tumors. Sonographic characteristics of a mature teratoma include (image 10 and image 11):

●The presence of a markedly hyperechoic nodule within the mass [42,46-52]. This appearance, particularly if the hyperechoic nodule has distal acoustic shadowing, is generally a strong indicator of a teratoma.

Teratomas may also be uniformly hyperechoic or have bright linear to punctate echoes (the latter sometimes referred to as the dermoid mesh [46]); these latter two appearances may occasionally be difficult to distinguish from bowel in the absence of peristalsis.

●A fluid-fluid level; if the echogenic fluid is nondependent, this is predictive of a teratoma, although this occurs in the minority of teratomas that have a fluid-fluid level [53].

●Calcification also can be present and may vary in size. Calcification alone is not a sufficient criterion to diagnose a dermoid and should be evaluated in the context of the overall appearance of the ovary [54].

●Floating globules is an uncommon appearance of teratomas but seems to be predictive [55].

●Absence of Doppler flow. Any mass with features of a teratoma must be evaluated with color Doppler imaging, since the identification of flow within the suspected teratoma makes the diagnosis quite unlikely and raises the possibility of malignant teratoma, exophytic lipoleiomyoma, or other cause for the mass [56].

When a mass has characteristic features of a dermoid, it is considered a "classic benign lesion" using the O-RADS system (O-RADS 2). However, these neoplasms may have features that can be mistaken for malignancy, especially by ultrasound imagers with less experience [57].

In one study evaluating the diagnostic performance of ultrasound for teratomas, 75 percent of teratomas exhibited more than one of these features [47]; there were no false-positive diagnoses of teratoma when more than one feature of teratomas were demonstrated on ultrasound.

The management of dermoid cysts is discussed elsewhere. (See "Ovarian germ cell tumors: Pathology, epidemiology, clinical manifestations, and diagnosis", section on 'Mature cystic teratomas'.)

Pedunculated leiomyoma — Pedunculated uterine leiomyomas (fibroids) usually appear as heterogeneous, hypoechoic, solid masses (image 12). They are more likely to be confused with an ovarian mass if the ipsilateral ovary is not seen and/or if there is cystic change within the fibroid. Visualization of the ipsilateral ovary, identification of the vascular fibroid pedicle arising from the uterus with Doppler [58], or additional studies with magnetic resonance imaging (MRI) can help with the diagnosis (see 'Step four: Is additional evaluation needed?' below). The management of leiomyomas is discussed elsewhere. (See "Uterine fibroids (leiomyomas): Epidemiology, clinical features, diagnosis, and natural history", section on 'Imaging and endoscopy'.)

Hydrosalpinx — A hydrosalpinx is a postinflammatory process in which fluid fills the fallopian tube. A confidently diagnosed hydrosalpinx is placed into the O-RADS 2 category. (See "Adnexal mass: Differential diagnosis", section on 'Hydrosalpinx'.)

On ultrasound, a hydrosalpinx usually appears tubular in shape and may have incomplete or partial "septations" (due to the wall of the tube folded in on itself) or nodules (thickened endosalpingeal folds) in its wall (image 13A-B) [59]. These septations and nodules may raise concern for ovarian malignancy if one does not recognize the extraovarian location of the mass [60]. The "waist sign," indentations along opposite walls, may be a useful feature for identifying a hydrosalpinx [60]. The management of hydrosalpinx is discussed elsewhere. (See "Approach to the patient with an adnexal mass", section on 'Management according to mass type'.)

Peritoneal inclusion cyst — Peritoneal inclusion cysts (also called multicystic inclusion cysts) are uncommon mesothelial lesions that appear as septated, cystic masses that surround the ovary, usually in patients with prior pelvic surgery and pelvic adhesions (image 14) [61,62]. Adhesions may be visualized on ultrasound as bands of tissue in the peritoneal cavity with surrounding fluid. When the mass has this characteristic appearance, it is regarded as an O-RADS 2 category.

Peritoneal inclusion cysts differ from neoplasms in that the fluid within the peritoneal inclusion cyst has angular margins with surrounding structures, insinuating between structures instead of causing mass effect upon them. The imager should look carefully for a distorted ovary (recognizable by its follicles) either within or at the edge of the mass when considering the diagnosis of peritoneal inclusion cyst. Sometimes, one or two follow-up imaging studies will be performed to achieve more confidence in the diagnosis. However, making the diagnosis of a peritoneal inclusion cyst on ultrasound can be difficult and often requires more than average experience and expertise; if characteristic features are not demonstrated or recognized, the mass justifies further evaluation under the presumption that it is an ovarian neoplasm. (See "Adnexal mass: Differential diagnosis", section on 'Other masses'.)

Malignancy

●Sonographic characteristics – Sonographic characteristics that are typically associated with an ovarian or fallopian tube malignancy include [63] (see 'IOTA Simple Rules' above):

•Solid component that is not hyperechoic and is often nodular or papillary – A solid component with blood flow is the most important feature of malignancy (image 15) [6].

•Septations, if present, that are irregularly thick (>2 to 3 mm) – A thick wall can be seen with malignancy, but many benign masses, such as hemorrhagic cysts or endometriomas, can also have a thick wall. Wall thickness alone does not seem to be a reliable feature for distinguishing benign from malignant ovarian masses.

•Presence of ascites.

•Peritoneal masses, enlarged nodes, or matted bowel (may be difficult to detect by ultrasound).

Historically, size of the mass was considered useful, with larger masses more likely to be malignant. While many ovarian malignancies are larger masses, as a general statement, this relationship has not been confirmed, as several studies have found no significant difference in size between malignant and benign masses [6,7]. This is because the overall size of a mass includes the cystic component, and the ROM is a function of the size of the solid component, not the cystic component. The data show that size of any suspected solid component of an adnexal mass is a risk factor for malignancy [64]. Therefore, a 10 cm simple cyst is not more worrisome than a 2 cm cyst with solid nodule. Similarly, a 10 cm mass with multiple features of a benign teratoma is not more worrisome than a 2 cm mass with multiple features of a cystadenocarcinoma because a dermoid cyst has no vascularized solid component.

●O-RADS 4 and 5 masses – Using O-RADS, masses are categorized as O-RADS 5 (high ROM) when there are ≥4 papillary projections in a unilocular cyst regardless of color Doppler findings, a multilocular cyst has a solid component of any size with demonstrable color Doppler signal, a solid smooth mass has very strong color Doppler signal, a solid irregular mass has any color Doppler signal, and/or when there are peritoneal nodules or abnormal peritoneal fluid associated with an adnexal mass [26]. (See 'O-RADS' above.)

Because sensitivity for malignancy is paramount, it is reasonable to also consider O-RADS 4 masses (intermediate ROM) as having sufficient suspicion for malignancy to justify oncologic surgical management. The observations that categorize an adnexal mass into O-RADS 4 include a solid smooth mass with minimal or moderate color Doppler flow, a multilocular cyst with solid component showing only minimal or no demonstrable color Doppler flow, a unilocular cyst with solid component and coexisting three or fewer papillary projections, and a variety of multilocular cysts based on size, inner wall irregularity, and color Doppler findings.

Step four: Is additional evaluation needed? — After passing through the preceding analysis, any mass that has not yet been classified should essentially have features putting it into the O-RADS 3 category (see 'O-RADS' above). Alternatively, it may be that the sonographic features have been indeterminate or equivocal or the ultrasound images are suboptimal. Follow-up with an ultrasound imaging expert [26], use of another imaging modality, or employing combinations of tests may be useful.

●Referral to a gynecologic oncologist – Referral to a gynecologic oncologist is often appropriate for these masses. This is discussed in detail elsewhere. (See "Approach to the patient with an adnexal mass", section on 'When to refer to a gynecologic oncologist'.)

●Additional imaging – Additional imaging with repeat ultrasonography, MRI, and/or referral to an ultrasound specialist (ie, a physician whose practice includes a focus on ultrasound assessment of adnexal lesions).

•Serial ultrasound – A repeat pelvic ultrasound performed after some interval of time is helpful to (1) ensure that the cyst was not initially mischaracterized, (2) distinguish between a mass that is measurably growing (favoring a benign neoplasm [eg, growing cystadenoma]) versus a cyst that is resolving or waxing/waning (favoring a non-neoplastic cyst) [65], and, in some cases, (3) alleviate patient concern.

Follow-up intervals vary widely. When a cyst has complex features that are worrisome for a neoplasm but may still potentially be due to a benign process (eg, hemorrhage), short interval follow-up sonographic evaluation can be invaluable. A follow-up sonogram in even a few weeks would help to assess for evolution of findings if due to hemorrhage and would not adversely affect the patient's clinical outcome if the findings prove secondary to tumor. By contrast, when one is fairly confident that initial diagnosis is "almost certainly benign," it is most cost effective to follow up with ultrasound in a relatively longer period of time (perhaps from three months to one year) to allow time for the cyst to change. If a cyst persists, but is stable in size over time (typically two years), one can conclude that the cyst is either a non-neoplastic cyst or an indolent process (eg, indolent cystadenoma) [65]. Further imaging beyond two years depends on clinical considerations on a case-by-case basis.

Specific follow-up intervals are based on the degree of malignancy risk and are discussed in detail separately. (See "Approach to the patient with an adnexal mass", section on 'Surveillance frequency'.)

In premenopausal patients, performing the follow-up sonogram approximately the second week of the menstrual cycle in the follicular phase (approximately cycle days 7 to 12) should help minimize confusing a new physiologic cyst (eg, hemorrhagic corpus luteal cyst) with the continued existence of a previous cyst. Practically, however, it is not always easy or necessary to schedule the follow-up sonogram at such a specific time, particularly if a patient's menstrual cycle is irregular.

•Magnetic resonance imaging – When ultrasound fails to lead to a confident diagnosis and when further characterization may change the gynecologic approach to management (eg, referral to a gynecologic oncologist), MRI evaluation may be helpful by demonstrating findings that lead to a confident diagnosis [33,38,66]. Emerging guidelines ("O-RADS MRI Risk Stratification System") help imagers assess adnexal observations using a risk stratification system modelled on the Breast Imaging Reporting and Data System (BI-RADS) [67].

For example, follow-up imaging with MRI may be indicated when the sonographer is unable to differentiate between a solid adnexal mass versus an exophytic leiomyoma (see 'Pedunculated leiomyoma' above). MRI is likely to help distinguish an exophytic myoma, which generally does not need operative intervention, from a solid adnexal mass, which almost always needs surgical removal. Another example is when a sonographer suspects that an adnexal mass is a benign cystic teratoma but does not have enough confidence in concluding that malignancy is practically excluded (eg, <1 percent chance of malignancy). (See 'Mature teratoma' above.)

Ultimately, the need for further MRI characterization of an adnexal mass evaluated sonographically depends on the experience and diagnostic confidence of the imager as well as the experience and surgical approach of the gynecologic surgeon.

●Other

•Tumor markers – Combined testing with ultrasound and serum tumor markers (eg, cancer antigen [CA] 125) appears have a higher specificity for ovarian malignancy than tumor markers alone. This is discussed in detail separately. (See "Approach to the patient with an adnexal mass", section on 'Role of tumor markers and multimodal tests'.)

•Multimodal tests – Multiple risk scoring systems have been proposed to differentiate between benign and malignant adnexal masses, including the Risk of Malignancy Index. These systems include sonographic features and other factors, such as menopausal status and serum CA 125. This is discussed in more detail separately. (See "Adnexal mass: Role of serum biomarkers in diagnosing epithelial carcinoma of the ovary, fallopian tube, or peritoneum", section on 'Biomarker panels for patients undergoing surgery'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ovarian and fallopian tube disease".)

SUMMARY AND RECOMMENDATIONS

●Etiology of adnexal masses – An adnexal mass (mass of the ovary, fallopian tube, or surrounding connective tissues) is a common gynecologic finding and may be physiologic or pathologic (table 2). Normal ovulatory physiology is the most common cause of an adnexal mass in premenopausal patients. Nonpathologic ovarian cysts are also routinely found in postmenopausal patients. (See 'Introduction' above and 'Etiology of adnexal masses' above.)

●Role of ultrasound – Pelvic ultrasound is typically the first-line imaging study used to characterize an adnexal mass. The goal of ultrasound is not to determine if the mass is "definitely" benign or malignant, but rather to determine whether the mass is "almost certainly benign" or whether the mass has some "reasonable chance of being malignant." (See 'Introduction' above and 'Overview' above.)

●Classification systems – There is no universally accepted classification system for adnexal masses; two systems include the International Ovarian Tumor Analysis (IOTA) Simple Rules and the Ovarian-Adnexal Reporting and Data System (O-RADS) ultrasound classification; this topic primarily uses the O-RADS system. (See 'Classification systems' above.)

•IOTA Simple Rules – The IOTA Simple Rules are based on a set of five ultrasound features indicative of a benign tumor (B-features) and five ultrasound features indicative of a malignant tumor (M-features) (image 5). (See 'IOTA Simple Rules' above.)

•O-RADS ultrasound – The O-RADS ultrasound system classifies adnexal masses into categories according to their of risk of malignancy (ROM): normal or almost certainly benign (O-RADS 1 or 2); low ROM (O-RADS 3); worrisome for malignancy (O-RADS 4 or 5). The 2022 O-RADS ultrasound assessment categories can be found online. (See 'O-RADS' above.)

●Characterization of an adnexal mass – The sonographic approach to the characterization of an adnexal mass that is not otherwise considered to be part of the normal ovary (O-RADS 1) can be summarized as a four-step approach:

•Step one – Determine if the mass is a simple cyst, thus, practically excluding the ROM (O-RADS 1, O-RADS 2). Other masses that may appear as a simple cyst include a cystadenoma or paraovarian/paratubal cyst. (See 'Step one: Is it a simple cyst?' above.)

•Step two – Determine if there are features that are consistent with another physiologic process (eg, corpus luteum, two simple cysts, hemorrhagic cyst). (See 'Step two: Are findings consistent with another physiologic process?' above.)

•Step three – Determine if there are features that are characteristic of specific pathologic entities, such as endometriomas, mature teratomas, hydrosalpinges, peritoneal inclusion cysts, and pedunculated fibroids. (See 'Step three: Are findings consistent with a specific pathologic process?' above.)

Adnexal masses that are suspicious for malignancy (eg, solid component with Doppler flow, irregularly thick septations) are those with findings that place the mass into O-RADS 4 or O-RADS 5 category. (See 'Malignancy' above.)

•Step four – Determine if additional evaluation is needed. After passing through the preceding analysis, any mass that has not yet been classified, has sonographic features that are indeterminate or equivocal, or has images that are suboptimal, should be classified as O-RADS 3. The opinion of an ultrasound specialist can be invaluable for further evaluation; alternatively, further evaluation with other imaging modalities or combinations of tests may be useful. (See 'Step four: Is additional evaluation needed?' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Douglas L Brown, MD, who contributed to an earlier version of this topic review.