Arch Gynecol Obstet (2014) 290:843–854 DOI 10.1007/s00404-014-3327-0
REVIEW
Adnexal masses: what is the role of ultrasonographic imaging? Maria Elisabetta Coccia • Francesca Rizzello Chiara Romanelli • Tommaso Capezzuoli
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Received: 13 November 2013 / Accepted: 17 June 2014 / Published online: 6 July 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Adnexal masses represent a common finding among both premenopausal and postmenopausal women. This article will concentrate on the importance of an accurate preoperative diagnosis of adnexal masses that may be encountered in the course of an assessment of the female pelvis. The ultrasonographic modalities including twodimensional, Doppler, three-dimensional and real-time four-dimensional approach, the accuracy of the technique, and the role of second-level exam will be discussed. Methods In this review, we searched for the most relevant articles on the topic with a special focus on the importance of an accurate preoperative diagnosis of adnexal masses, the different ultrasonographic modalities, and the role of second-level exam. Results The primary goal of diagnostic evaluation is to exclude malignancy. Furthermore, differentiation among pelvic masses with non-malignant features is relevant as well since suitable counseling and treatment depend on the suspected histology. Ultrasound represents the first-line modality for assessing adnexal masses and showed a very accurate examination. Ultrasound, performed by experienced operators, is effective in the morphologic evaluation of the adnexal masses and is useful in discriminating between benign and malignant lesions. Second-level exams may include assessment by an experienced ultrasound examiner, magnetic resonance imaging, and computed tomography.
M. E. Coccia F. Rizzello (&) C. Romanelli T. Capezzuoli Department of Clinical and Experimental Biomedical Sciences, University of Florence, Largo Brambilla, 3, 50134 Florence, Italy e-mail: [email protected]
Conclusion Ultrasound represents the first-line modality for assessing adnexal masses. Predicting the nature of an adnexal mass is essential regarding counseling, clinical management and surgical planning in such patients. Pattern recognition can accurately diagnose the majority of the benign masses and malignancies. Keywords Gynecology Gynecologic cancer Adnexal mass Ovarian cyst Ultrasonography
Introduction Adnexal masses represent a common finding among both premenopausal and postmenopausal women. According to International Ovarian Tumor Analysis (IOTA), an adnexal lesion is defined as ‘the part of an ovary or an adnexal mass that is judged from an assessment of ultrasound images to be inconsistent with normal physiologic function’ [1]. The reported prevalence varies widely depending upon the population studied, the criteria employed and the ultrasound equipment. In a random sample of asymptomatic women 25–40 years, adnexal lesions with the largest diameter of at least 25 mm were found in 7.8 % of cases, with a prevalence of ovarian cysts of 6.6 %. Four out of five ovarian cysts disappeared spontaneously within 3 months [2]. Ovarian Cancer Screening Trial observed that 21.2 % of healthy postmenopausal women had abnormal ovarian morphology, either simple or complex [3]. Castillo evaluated 8,794 asymptomatic postmenopausal women with ultrasound and identified 215 (2.5 %) women with simple unilocular adnexal cyst. Among 104 patients who underwent conservative follow-up, 46 (44 %) had a spontaneous resolution (74 % of them within 2 years) [4].
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Patients with an adnexal mass may present with varying symptoms. In other cases, pelvic masses may be discovered as a result of screening in asymptomatic women or incidentally during investigation for other reasons [5]. Although evaluation is often aimed at distinguishing benign from malignant masses, the majority of adnexal masses are benign. About 90 % of adnexal masses can be adequately characterized with ultrasonography alone [6]. The wider use of ultrasound means that an increasing proportion of these cysts will come to the attention of gynecologists. The differential diagnosis of an adnexal mass includes benign and malignant gynecologic and nongynecologic etiologies. Predicting the nature of an adnexal mass is central to decisions regarding clinical management and surgical planning in such patients [7]. Ultrasonography is the first-line modality for assessing adnexal masses in the vast majority of patients. This paper will concentrate on the importance of an accurate preoperative diagnosis of adnexal masses. The ultrasonographic modalities including two-dimensional, Doppler, threedimensional (3D) and real-time four-dimensional (4D) approach, the accuracy of the technique, and the role of second-level exam will be discussed.
Importance of accurate preoperative diagnosis The primary goal of diagnostic evaluation of adnexal masses is to exclude malignancy. Ovarian cancer is the most lethal of the gynecologic malignancies, with an overall 5-year survival rate of less than 40 % [8]. According to ACOG guidelines (2008), women with adnexal masses have a 5–10 % risk of requiring surgery, and those who undergo surgery have a 13–21 % chance of being diagnosed with ovarian cancer [9].
Malignant adnexal masses A standardized method for preoperative identification of probable malignant masses would allow optimization of first-line treatment for women with ovarian cancer. The discrimination between benign and malignant adnexal masses allows a rapid referral of women with suspected cancers to regional cancer centers and consequently improves morbidity. Women with ovarian cancer who are treated by physicians who have advanced training and expertise in gynecologic cancer (e.g., gynecologic oncologists) have better survival rates than women treated by physicians without such training or expertise. An optimal debulking, lymph node dissection and surgical staging are important prognostic factors in ovarian cancer. Thus, appropriate and
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Fig. 1 Ovarian cancer
timely referral to a gynecologic oncologist has been proven to increase survival in patients with ovarian cancer [1, 10]. Although there is considerable overlap in morphologic characteristics and corresponding imaging, features suggestive of malignancy include mixed echogenicity, several papillary projections or thick septa, solid cystic components or a large soft-tissue component with necrosis, bizarre, irregular vessels with changing calibers (Fig. 1) [11].
Benign adnexal masses Most ovarian masses in reproductive-aged women are benign, and many are functional cysts that resolve on their own. This may be extended also to many postmenopausal women with simple cysts. Differentiation among the different pelvic masses with non-malignant features is relevant as well since suitable counseling and treatment depend on the suspected histology. Ultrasonographic evaluation before surgery is important to reduce the number of unnecessary surgical procedures. Patients with suspected benign cysts may be surgically treated by a general gynecologic surgeon [1]. Possible benefits to surgical excision in patients with benign masses in the absence of symptoms include preventing acute events such as ovarian torsion (commonly associated with cystadenoma or teratoma) or spontaneous cyst rupture (as with mature cystic teratoma, endometrioma) [1]. The ultrasonographic appearance, the clinical relevance and perspective of the most common benign gynecologic masses are discussed in the following section. These include functional ovarian cysts, ovarian endometriomas, dermoid cysts, parovarian and paratubal cysts, peritoneal
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inclusion cysts, hydrosalpinges, cystadenomas, cystadenofibromas, and ectopic pregnancies. Other causes for benign adnexal masses are postoperative masses like abscesses, hematomas, lymphoceles, urinomas, bladder diverticula, ureteral diverticula, seromas, postpartum complications, subserosal fibroids, congenital malformations of the ipsilateral Mt‹ llerian duct, malformations of ipsilateral fallopian tube, round ligament, kidney, or ureter, lobulated accessory supernumerary ovaries, appendiceal abscess or mucocele, pelvic kidneys, and nerve sheath tumors (Table 1).
Table 1 Most common causes for adnexal masses Type
Benign
Malignant N
Most common gynecologic cause
Functional ovarian cysts
Germ cell tumor
Ovarian endometrioma
Dysgerminoma
Dermoid cysts
Immature teratoma
Parovarian and paratubal cysts
Sex cord stromal tumor
Peritoneal inclusion cyst
Granulosa cell tumor
Hydrosalpinges
Epithelial ovarian carcinoma
Tuboovarian abscess
Cystadenoma (mucinous cystadenoma, serous cystadenoma)
Invasive epithelial
Cystadenofibroma
Fallopian tube carcinoma
Ectopic pregnancy Leiomyomata Other causes for benign adnexal masses
Borderline or low malignant potential
Functional ovarian cyst By far the most common cystic ovarian lesions, among women of reproductive age, are benign functional ovarian cysts. The possibility of dealing with a luteal or follicular cyst must be considered in the presence of irregular periods. Functional cysts include follicular cysts, corpus luteum cysts, and hemorrhagic cysts. Ultrasonographic aspect On ultrasound, follicular cysts present as simple unilocular, round, anechoic cysts with a thin, smooth wall and a maximum diameter of 5 cm. For these types of cysts, even in post menopausal women, the probability of malignancy is extremely low [12]. A corpus luteum cyst has a thick, hyperechoic, and occasionally corrugated wall and usually has hemorragic content. The color Doppler sonography shows a typical vascular ‘ring of fire’ [13]. An hemorrhagic cyst is generally due to expanding hemorrhage within a corpus luteum or other functional cyst. It may evolve into various stages of acute hemorrhage, clot formation, and retraction, thus giving rise to changing sonographic appearances. Hemorrhagic lesion is characterized by the presence of clots, fibrin strands, retracting thrombus, and fluid levels. The internal architecture is responsible for their appearance characterized by low-level echogenic content (‘mesh-like’ or thin ‘cobweb’-like appearance) (Fig. 2) [14]. Management Surgical management of these cysts may not be beneficial in comparison with either medical treatment in the case of a luteal mass or expectant management in cases of a simple
Abscesses, hematomas, lymphoceles Urinomas, bladder diverticulum, ureteral diverticulum, seromas Postpartum complications Subserosal fibroids Congenital malformation of the ipsilateral Mu¨llerian duct Malformation of ipsilateral fallopian tube, round ligament, kidney, or ureter Lobulated accessory supernumerary ovaries Appendiceal abscess or mucocele Pelvic kidney Nerve sheath tumor
Fig. 2 Functional cyst
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The ultrasound-based diagnosis of ovarian endometrioma involved the visualization of persistent round-shaped homogeneous hypoechoic ‘tissue’ with low-level echoes within the ovary. Endometriomas contents may show different patterns ranging from anechoic to solid, depending on the amount of blood and its organization (Fig. 3) [24, 25]. In most cases, endometrioma shows a ‘ground-glass’ pattern, with homogeneously dispersed echogenic cystic content [26].
surgery before in vitro fertilization (IVF)/intra cytoplasmatic sperm injection (ICSI) treatment is considered to be the ‘gold standard’ in symptomatic women with ovarian endometrioma and in asymptomatic patients with endometriomas C4 cm [27]. In any case, the management of ovarian endometriomas in women who desire a pregnancy is still a matter of debate [28, 29]. On one hand, the removal of endometriomas in infertile patients often improves reproductive outcomes, with a reported pregnancy rate after surgery alone of 37.4 % [30]. On the other hand, women undergoing surgery for endometriosis have to cope with both the endometrioma-related injury and the damage caused by surgery [31]. Moreover, as a consequence of cystectomy, ovaries seem to exhibit reduced responsiveness to hyperstimulation with gonadotropins. These effects are clinically more relevant in patients with bilateral endometriomas who undergo surgery more than once [31–37]. The patient should be counseled regarding the risks of reduced ovarian function after surgery and the decision should be reconsidered if she has had previous ovarian surgery [27]. Malignant transformation has been documented in 0.3–0.8 % of patients with ovarian endometriosis [38]. The most frequent histotypes of ovarian cancer deriving from endometriosis are represented by clear-cell adenocarcinoma and endometrioid carcinoma [39].
Management
Dermoid cyst
Management of ovarian endometriomas depends on size of the cyst, previous surgery for endometrioma, associated symptoms, severity of the symptoms, age of the patient, and desire to get pregnant or not. According to the European Society of Human Reproduction and Embryology (ESHRE) guidelines for the diagnosis and treatment of endometriosis, laparoscopic
Ovarian dermoid cyst (mature cystic teratoma) is the most frequent benign ovarian germ cell tumor identified during the adolescent and the reproductive period, comprising 5–25 % of all ovarian masses [40]. It is derived from all three germ cell layers (ectodermal layer, mesodermal and endodermal layer). The ectodermal component is often the most represented [41]. Teratomas vary in size from few millimeters to more than 40 cm; they are usually unilateral but in about 1 in 10 cases may develop in both ovaries.
cyst [15]. According to a Cochrane of 2009 [16], watchful waiting for two or three cycles is appropriate. During the menopause, the majority of simple ovarian cysts resolve spontaneously or persist unaltered on followup. Moreover, these cysts can be followed conservatively because their risk for malignant transformation is low [17]. Ovarian endometrioma Endometriosis is common, with an estimated incidence of approximately 10 % of the general female population [18–21]. Approximately 15–44 % of women with endometriosis have ovarian endometriomas [22, 23]. Ultrasonographic aspect
Ultrasonographic aspect Dermoids have a wide spectrum of sonographic appearances depending on which elements are present. Certain sonographic features occur with a degree of constancy and that allow a confident diagnosis: focal or diffuse hyperechoic components, hyperechoic lines and dots, and area of acoustic shadowing, with no internal flow at color Doppler Ultrasound (Fig. 4) [42, 43]. Management
Fig. 3 Endometrioma
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When surgical management is decided, intraperitoneal leakage of the cystic contents may result in chemical
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Fig. 4 Dermdoid cyst
peritonitis [44, 45]. The reported 15–28 % risk of iatrogenic intraoperative rupture goes far beyond the risk for spontaneous rupture [46]. Malignant transformation of dermoid cysts has been recorded as occurring in 1–2 % of cases. The most common form of malignant transformation is squamous cell carcinoma, which occurs in about 75 % of cases, while adenocarcinoma is rare, with an incidence of 7 % [47]. Hydrosalpinx Hydrosalpinx is characterized by a collection of watery fluid in a uterine tube. It is associated with obliteration of the fimbriae and dilatation of the fallopian tube, in particular the ampullary and infundibular portions. The tube usually contains clear, serous fluid. Ultrasonographic aspect The ultrasound appearance is typical and can be easily distinguished from ovarian abnormalities. It varies according to extension and the stage of the inflammatory process. Frequently the adnexal mass is cystic, tubular, elongated, with incomplete septations. Sometimes the walls present multiple hyperechoic mural nodules (beads-on-astring sign) and/or short linear projections (cogwheel sign) (Fig. 5). In some cases the ovary may also be involved in the disease process to form a chronic tuboovarian mass [11]. Management The presence of hydrosalpinx impairs IVF outcomes by decreasing the implantation and pregnancy rates. The cause of a low pregnancy rate could be due to mechanical, chemical or toxic effects of the tubal fluid. Correction of the hydrosalpinx may improve the outcome of IVF. The
Fig. 5 Paraovarian cyst in menopausal patient
most suitable surgical procedure is still debated. Laparoscopic removal of the hydrosalpinx (salpingectomy) before IVF is the procedure of choice. Other techniques include hysteroscopic proximal tubal occlusion, laparoscopic occlusion of the tube proximally close to the uterus (preferable when the distal fallopian tube is buried in dense and severe adhesions), and transvaginal aspiration of hydrosalpinx. The proper selection of patients for surgical treatment and for the type of surgical technique is essential to achieve good results [48]. Cystadenoma Cystadenoma is very common and may mimic a physiologic cyst. Serous cystadenomas constitute 20 % of all benign ovarian neoplasms and are usually encountered during the reproductive years. In 7–12 % of patients, these tumors are bilateral [11]. Ultrasonographic aspect Their ultrasonographic appearance is similar to functional cysts, except for the fact that they are larger in size and do not go through spontaneous resolution (Fig. 6) [40]. They appear as thin-walled, unilocular or multilocular cysts with anechoic content. The inner lining may be smooth or have areas with grossly visible papillary projections. Septa can be present, but usually they are thin [11]. Mucinous cystadenoma is less common, almost always simple or septate, thin-walled, multilocular, with low-level echoes cystic content, and no solid areas. The size may reach large dimensions, until 40–50 cm [49]. Papillary projections are almost always absent. The content of the single locules may vary depending on the difference in the
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Fig. 6 Peritoneal inclusion cyst Fig. 8 Serous cystadenoma
Ultrasonographic aspect On ultrasonography it appears as a complex mass: unilocular or multilocular, with thick papillary projections. Often solid tissue (nodules) within the mass can be found. In 50 % of the cystadenofibroma, intracystic blood flow is seen, from slight to moderate [50] (Fig. 8). Ectopic pregnancy
Fig. 7 Hydrosalpinx
chemical composition of fluids, rather than the difference in viscosity. The sonographic detection of variable echogenicity in the contents of an adnexal multilocular cyst is strongly suggestive of a mucinous tumor (Fig. 7) [11]. Management Preoperative knowledge of the mucinous nature of the tumor is of crucial importance to prevent spillage. The occurrence of spillage of mucin may cause spread of cells in malignant tumors and Pseudomyxoma peritonei. This is a rare clinical entity characterized by diffuse intraabdominal gelatinous collections with mucinous implants on the peritoneal surfaces and omentum [49]. Cystadenofibroma Some authors consider cystadenofibromas a variant of serous cystadenomas. They are found in patients aged 15–65 years (mean 30.7 years) and constitute nearly half of all benign ovarian cystic serous tumors.
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Ectopic pregnancy is defined as a pregnancy implanted outside of uterine cavity [51, 52]. Approximately 1–2 % of all pregnancies in Europe and the USA are ectopic. In the Western world tubal ectopic pregnancy remains the most common cause of maternal mortality in the first trimester of pregnancy [52, 53]. Ultrasonographic aspect At Ultrasound, the extra-uterine gestational sac with trophoblastic tissue might appear as an extra-ovarian thickwalled adnexal mass (the tubal ring sign) [11] (Fig. 9). Up to 20 % of patients with ectopic pregnancy demonstrate an intrauterine pseudogestational sac. Parovarian and paratubal cyst Parovarian and paratubal cysts may arise from mesonephric (Wolffian) structures, paramesonephric (Mu¨llerian) structures, or mesothelial inclusions [11]. Ultrasonographic aspect Their sonographic appearance is characterized by thin, regular walls and anechoic content, that are not surrounded
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Fig. 9 Large mucinous cystadenoma
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Fig. 11 Ectopic pregnancy
level echoes due to hemorrhagic or proteinaceous fluid [11]. Differential diagnosis includes parovarian cysts and hydrosalpinx [54, 55] (Fig. 11). Ultrasonography of the adnexa: two-dimensional, Doppler, three-dimensional (3D) and real-time four-dimensional (4D)
Fig. 10 Cystadenofibroma
by ovarian stroma. Hormonal cycle does not affect their size. The most common paramesonephric cyst is the hydatid of Morgagni (Fig. 10). Peritoneal inclusion cyst Peritoneal inclusion cysts occur mainly in women with a history of previous abdominal surgery, pelvic inflammatory disease or endometriosis. In patients with peritoneal adhesions, fluid collections can create cysts of various shapes. Fluid may entrap the ovaries with or without ovarian cysts, resulting in a large adnexal mass. Ultrasonographic aspect Sonographically they appear as extra-ovarian, multilocular pelvic cysts, with regular wall and irregular shape. The content is usually anechoic; sometimes it contains low-
Transvaginal or transabdominal ultrasound examination is recommended as part of the initial workup of an adnexal/ ovarian mass [56]. Despite advances in technology, conventional gray-scale transvaginal sonography (TVS) remains the most common imaging modality for the evaluation of adnexal masses. Through the use of high-frequency probes it allows a detailed morphologic view. The use of Doppler analysis for the purposes of colorflow mapping and characterization of waveforms was to evaluate neovascularity of ovarian neoplasms. The addition of Doppler techniques appears to offer improved specificity in the diagnosis of adnexal masses over two-dimensional ultrasonography. Doppler imaging includes color-flow morphology, pulsed Doppler, power Doppler, and power Doppler angiography [1]. The resistance index, the pulsatility index, and the maximum systolic velocity are parameters that objectively quantify vessel flow characteristics to distinguish high- and low-resistance vessels. The IOTA Group suggested the use of a subjective semiquantitative assessment of flow to describe the vascular features of adnexal masses [26]. Malignant lesions usually produce a significant increase in color Doppler flow signals secondary to angiogenesis not only at the periphery but also in the central regions of the mass, including septa and solid areas [57]. However, because of the overlap of flow characteristics among benign, borderline, and malignant neoplasms, a firm differential diagnosis based on Doppler evaluation alone is not possible [1].
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Fig. 12 Three-dimensional ultrasonography
The availability of three-dimensional (3D) and real-time four-dimensional (4D) ultrasound has provided a new way of studying adnexal masses (Fig. 12). The system offers several analysis tools, such as multiplanar imaging, surface and volume rendering, semi-automated volume calculation and quantification of echogenicity of the adnexal mass [11]. Moreover, three-dimensional ultrasound allows the off-line assessment of stored 3D/4D volumes. Three-dimensional power Doppler examination offers the possibility to visualize and quantify blood flow in adnexal masses. Recently Perez observed that 3D-power Doppler angiography values increase progressively, but not significantly, with the stage of malignancy in complex ovarian masses [58]. Accuracy of ultrasonography and scoring systems In the hands of an experienced ultrasound examiner, the socalled ‘pattern recognition’, that is the subjective evaluation of ultrasound findings, is an excellent method for discrimination between benign and malignant masses. A multi-centre prospective trial (IOTA) concluded that pattern recognition of ultrasound images by a trained observer was superior to serum Ca-125 for discrimination between benign and malignant adnexal masses [59]. Sokalska et al. [60] examined the sensitivity and specificity of subjective evaluation of gray-scale and Doppler ultrasound findings when applied by experienced ultrasound examiners. The study was realized within the
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framework of the IOTA study and included a total of 1,066 women, of whom 800 had a benign mass and 266 had a malignant mass. A specific diagnosis based on ultrasound findings was suggested in 899 (84 %) tumors. The specificity was high for all diagnoses (94–100 %). The sensitivity was highest for benign teratoma/dermoid cysts (86 %), hydrosalpinges (86 %), peritoneal pseudocysts (80 %) and endometriomas (77 %), and lowest for functional cysts (17 %), paraovarian/parasalpingeal cysts (14 %), benign rare tumors (11 %), adenofibromas (8 %), simple cysts (6 %) and struma ovarii (0/5). The positive and negative likelihood ratios with regard to dermoid cysts, hydrosalpinges and endometriomas were 68.2 and 0.14, 38.9 and 0.15, and 33.3 and 0.24, respectively. The authors concluded that using subjective evaluation of gray-scale and Doppler ultrasound findings it is possible to make an almost conclusive diagnosis of a dermoid cyst, endometrioma and hydrosalpinx. Many other adnexal pathologies can be recognized but not confidently confirmed or excluded. Initial reports on 3D ultrasonography suggest a possible improved performance compared to 2D ultrasonography. 3D ultrasonography showed sensitivities ranging from 78 to 100 %, specificities from 78 to 92 % and negative predictive values of 95–99 % in the identification of malignancy among women with an adnexal mass. Further studies are required to assess whether 3D sonography may be appropriate in the triage of the intermediate-risk adnexal mass identified by two-dimensional imaging [1].
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Accuracy of pelvic ultrasonography and image quality are both equipment- and operator-dependent. It is important to be aware that studies reporting on the accuracy of ultrasonography in discriminating benign from malignant adnexal masses are typically undertaken under optimal conditions, using contemporary high-resolution equipment with a limited number of experts performing and interpreting the scans. To overcome some of the subjective elements of interpretation and improve reproducibility, a variety of predictive models with the use of scoring systems, logistic regression analysis, neural networks, and support vector machines have been developed to increase the accuracy of the preoperative assessment of the adnexal mass. The three most commonly used and validated indexes are Sassone scoring system [61], Ovarian Tumor Index (OTI) [62], and the risk of malignancy index (RMI), recommended by the Royal College of Obstetricians and Gynaecologists [5]. Unfortunately, when these models were tested prospectively, they performed less well than was originally reported [63–68]. IOTA and simple rules The IOTA study group developed two logistic regression models that performed as well in new centers as in the units where the models were first developed [69]. However, no model or biochemical marker of ovarian malignancy has been shown to be superior to subjective assessment of gray-scale and color Doppler ultrasonic findings by an experienced ultrasound examiner. The expertise of experienced ultrasound examiners is not easily transferred to less experienced examiners. Therefore, proper teaching and training in ultrasonography remain essential [70]. The simple ultrasound rules proposed by the IOTA group to discriminate between benign and malignant adnexal masses seem more generalizable. This method is based on five ultrasonic features to predict a malignant tumor (M features): irregular solid tumor (M1), ascites (M2), at least four papillary structures (M3), irregular multilocular solid tumor with a largest diameter of at least 100 mm (M4), and very high color content on color Doppler examination (M5). Five ultrasonic features were adopted to predict a benign tumor (B features): unilocular cyst (B1), presence of solid components for which the largest solid component is \7 mm in largest diameter (B2), acoustic shadows (B3), smooth multilocular tumor (B4), and no detectable blood flow on Doppler examination (B5). If one or more M features were present in the absence of a B feature, we classified the mass as malignant (rule 1). If one or more B features were present in the absence of an M feature, we
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classified the mass as benign (rule 2). If both M features and B features were present, or if none of the features was present, the simple rules were inconclusive (rule 3) [71]. A study observed that the rules reliably discriminated between benign and malignant adnexal masses. They did so just as well as subjective assessment by an experienced ultrasound examiner did [72]. We should observe that, to increase the specificity of ultrasound, reproducible and accurate method for the sonographic evaluation of ovarian masses must be implemented. This moved to improve and standardize reporting in gynecological ultrasound. In light of this, the IOTA study group provided a reproducible standardized methodology to describe adnexal pathology when performing transvaginal ultrasound [26]. A standard reporting in gynecological ultrasound may develop into a very promising tool to produce a common language for scientific groups studying adnexal masses and thus to allow comparisons of results. Role of second-level exam Nevertheless, even in the most experienced hands, 10 % of adnexal masses are still difficult to classify on TVS [6]. According to Timmerman et al. [72] for tumors that cannot be classified using simple rules, ultrasound examination by an expert examiner might be useful. The clinical practice guideline by Dodje et al. [73] confirmed that TVS should be the modality of first choice in patients with a suspicious isolated ovarian mass. To help clarify malignant potential in patients in whom ultrasonography may be unreliable, magnetic resonance imaging (MRI) is the most appropriate test. In cases in which extraovarian disease is suspected or needs to be ruled out, computed tomography (CT) is the most useful technique. Secondary testing may include also CA125, other biomarkers combinations and Proteomics [73, 74]. The CA 125 is the most extensively investigated serum marker for ovarian cancer. Elevated serum CA125 has been reported in a variety of benign conditions. Moreover, serum CA125 is elevated in only 50 % of early-stage ovarian cancers [73]. As such, it has a low specificity, especially in premenopausal women [75–77]. To increase specificity of Ca125 for detecting ovarian carcinoma, a variety of serum proteins have been identified. Proteomic technology has been investigated to determine if serum protein profiling patterns could be used to distinguish between benign and malignant adnexal masses [1]. In September 2009, the Food and Drug Administration approved a serum-based test called OVA1 for the presurgical evaluation of a woman with an ovarian mass. The test combines five separate serum protein marker
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(Beta-2 microglobulin, CA 125, apolipoprotein A1, Prealbumin and Transferrin) results as well as menopausal status into a single numerical score between 0 and 10 to indicate the likelihood that the pelvic mass is benign or malignant. It is important to emphasize that neither serum biomarkers nor more complex tests can replace clinical judgment and further confirmatory studies are underway [1].
(c)
6.
7. Conclusion Ultrasound represents the first-line modality for assessing adnexal masses. Predicting the nature of an adnexal mass is essential regarding counseling, clinical management and surgical planning in such patients. Pattern recognition can accurately diagnose some of the benign masses and malignancies. However, the sonographic appearance of an ovarian mass is not pathognomonic in 10 % of adnexal masses. In these indeterminate cases a second-level exam may be beneficial. Patient’s age, symptoms, features of menstrual periods, and family history should always be taken into consideration when evaluating an adnexal mass. Crucial points 1.
2.
3.
4. 5.
Transvaginal ultrasound showed a very accurate examination, but it is highly operator and equipment dependent; The primary goal of ultrasonographic evaluation of adnexal masses is to exclude malignancy; adnexal masses with ultrasonographic features suggestive of malignancy should be referred to gynecologic oncologists; Differentiation among the different pelvic masses with benign features is relevant as well since suitable counseling and treatment depend on the suspected histology; Second-level exams may include assessment by an experienced ultrasound examiner, MRI, and CT; Using subjective evaluation based on gray-scale and color or power Doppler features, endometriomas, dermoid cysts, and hydrosalpinges can be correctly categorized: (a)
(b)
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Endometrioma’s sonographic features: persistent round-shaped homogeneous hypoechoic cyst with low-level echoes within the ovary, internal homogeneous ground-glass or low-level echoes, without internal color Doppler flow; Dermoid’s sonographic features: focal or diffuse hyperechoic components, hyperechoic lines and dots, and area of acoustic shadowing, with no internal flow at color Doppler Ultrasound;
Hydrosalpinx sonographic features: tubular, elongated, with incomplete septations. Sometimes multiple hyperechoic mural nodules (beads-on-a-string sign), and/or short linear projections (cogwheel sign);
Doppler technique, 3D and 4D ultrasonography appears to improve specificity in the diagnosis of adnexal masses; No model or biochemical marker of ovarian malignancy has been shown to be superior to subjective assessment of gray-scale and color Doppler ultrasonography.
Conflict of interest interest to report.
None of the authors have financial conflicts of
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REVIEW
Adnexal masses: what is the role of ultrasonographic imaging? Maria Elisabetta Coccia • Francesca Rizzello Chiara Romanelli • Tommaso Capezzuoli
•
Received: 13 November 2013 / Accepted: 17 June 2014 / Published online: 6 July 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Adnexal masses represent a common finding among both premenopausal and postmenopausal women. This article will concentrate on the importance of an accurate preoperative diagnosis of adnexal masses that may be encountered in the course of an assessment of the female pelvis. The ultrasonographic modalities including twodimensional, Doppler, three-dimensional and real-time four-dimensional approach, the accuracy of the technique, and the role of second-level exam will be discussed. Methods In this review, we searched for the most relevant articles on the topic with a special focus on the importance of an accurate preoperative diagnosis of adnexal masses, the different ultrasonographic modalities, and the role of second-level exam. Results The primary goal of diagnostic evaluation is to exclude malignancy. Furthermore, differentiation among pelvic masses with non-malignant features is relevant as well since suitable counseling and treatment depend on the suspected histology. Ultrasound represents the first-line modality for assessing adnexal masses and showed a very accurate examination. Ultrasound, performed by experienced operators, is effective in the morphologic evaluation of the adnexal masses and is useful in discriminating between benign and malignant lesions. Second-level exams may include assessment by an experienced ultrasound examiner, magnetic resonance imaging, and computed tomography.
M. E. Coccia F. Rizzello (&) C. Romanelli T. Capezzuoli Department of Clinical and Experimental Biomedical Sciences, University of Florence, Largo Brambilla, 3, 50134 Florence, Italy e-mail: [email protected]
Conclusion Ultrasound represents the first-line modality for assessing adnexal masses. Predicting the nature of an adnexal mass is essential regarding counseling, clinical management and surgical planning in such patients. Pattern recognition can accurately diagnose the majority of the benign masses and malignancies. Keywords Gynecology Gynecologic cancer Adnexal mass Ovarian cyst Ultrasonography
Introduction Adnexal masses represent a common finding among both premenopausal and postmenopausal women. According to International Ovarian Tumor Analysis (IOTA), an adnexal lesion is defined as ‘the part of an ovary or an adnexal mass that is judged from an assessment of ultrasound images to be inconsistent with normal physiologic function’ [1]. The reported prevalence varies widely depending upon the population studied, the criteria employed and the ultrasound equipment. In a random sample of asymptomatic women 25–40 years, adnexal lesions with the largest diameter of at least 25 mm were found in 7.8 % of cases, with a prevalence of ovarian cysts of 6.6 %. Four out of five ovarian cysts disappeared spontaneously within 3 months [2]. Ovarian Cancer Screening Trial observed that 21.2 % of healthy postmenopausal women had abnormal ovarian morphology, either simple or complex [3]. Castillo evaluated 8,794 asymptomatic postmenopausal women with ultrasound and identified 215 (2.5 %) women with simple unilocular adnexal cyst. Among 104 patients who underwent conservative follow-up, 46 (44 %) had a spontaneous resolution (74 % of them within 2 years) [4].
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Patients with an adnexal mass may present with varying symptoms. In other cases, pelvic masses may be discovered as a result of screening in asymptomatic women or incidentally during investigation for other reasons [5]. Although evaluation is often aimed at distinguishing benign from malignant masses, the majority of adnexal masses are benign. About 90 % of adnexal masses can be adequately characterized with ultrasonography alone [6]. The wider use of ultrasound means that an increasing proportion of these cysts will come to the attention of gynecologists. The differential diagnosis of an adnexal mass includes benign and malignant gynecologic and nongynecologic etiologies. Predicting the nature of an adnexal mass is central to decisions regarding clinical management and surgical planning in such patients [7]. Ultrasonography is the first-line modality for assessing adnexal masses in the vast majority of patients. This paper will concentrate on the importance of an accurate preoperative diagnosis of adnexal masses. The ultrasonographic modalities including two-dimensional, Doppler, threedimensional (3D) and real-time four-dimensional (4D) approach, the accuracy of the technique, and the role of second-level exam will be discussed.
Importance of accurate preoperative diagnosis The primary goal of diagnostic evaluation of adnexal masses is to exclude malignancy. Ovarian cancer is the most lethal of the gynecologic malignancies, with an overall 5-year survival rate of less than 40 % [8]. According to ACOG guidelines (2008), women with adnexal masses have a 5–10 % risk of requiring surgery, and those who undergo surgery have a 13–21 % chance of being diagnosed with ovarian cancer [9].
Malignant adnexal masses A standardized method for preoperative identification of probable malignant masses would allow optimization of first-line treatment for women with ovarian cancer. The discrimination between benign and malignant adnexal masses allows a rapid referral of women with suspected cancers to regional cancer centers and consequently improves morbidity. Women with ovarian cancer who are treated by physicians who have advanced training and expertise in gynecologic cancer (e.g., gynecologic oncologists) have better survival rates than women treated by physicians without such training or expertise. An optimal debulking, lymph node dissection and surgical staging are important prognostic factors in ovarian cancer. Thus, appropriate and
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Fig. 1 Ovarian cancer
timely referral to a gynecologic oncologist has been proven to increase survival in patients with ovarian cancer [1, 10]. Although there is considerable overlap in morphologic characteristics and corresponding imaging, features suggestive of malignancy include mixed echogenicity, several papillary projections or thick septa, solid cystic components or a large soft-tissue component with necrosis, bizarre, irregular vessels with changing calibers (Fig. 1) [11].
Benign adnexal masses Most ovarian masses in reproductive-aged women are benign, and many are functional cysts that resolve on their own. This may be extended also to many postmenopausal women with simple cysts. Differentiation among the different pelvic masses with non-malignant features is relevant as well since suitable counseling and treatment depend on the suspected histology. Ultrasonographic evaluation before surgery is important to reduce the number of unnecessary surgical procedures. Patients with suspected benign cysts may be surgically treated by a general gynecologic surgeon [1]. Possible benefits to surgical excision in patients with benign masses in the absence of symptoms include preventing acute events such as ovarian torsion (commonly associated with cystadenoma or teratoma) or spontaneous cyst rupture (as with mature cystic teratoma, endometrioma) [1]. The ultrasonographic appearance, the clinical relevance and perspective of the most common benign gynecologic masses are discussed in the following section. These include functional ovarian cysts, ovarian endometriomas, dermoid cysts, parovarian and paratubal cysts, peritoneal
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inclusion cysts, hydrosalpinges, cystadenomas, cystadenofibromas, and ectopic pregnancies. Other causes for benign adnexal masses are postoperative masses like abscesses, hematomas, lymphoceles, urinomas, bladder diverticula, ureteral diverticula, seromas, postpartum complications, subserosal fibroids, congenital malformations of the ipsilateral Mt‹ llerian duct, malformations of ipsilateral fallopian tube, round ligament, kidney, or ureter, lobulated accessory supernumerary ovaries, appendiceal abscess or mucocele, pelvic kidneys, and nerve sheath tumors (Table 1).
Table 1 Most common causes for adnexal masses Type
Benign
Malignant N
Most common gynecologic cause
Functional ovarian cysts
Germ cell tumor
Ovarian endometrioma
Dysgerminoma
Dermoid cysts
Immature teratoma
Parovarian and paratubal cysts
Sex cord stromal tumor
Peritoneal inclusion cyst
Granulosa cell tumor
Hydrosalpinges
Epithelial ovarian carcinoma
Tuboovarian abscess
Cystadenoma (mucinous cystadenoma, serous cystadenoma)
Invasive epithelial
Cystadenofibroma
Fallopian tube carcinoma
Ectopic pregnancy Leiomyomata Other causes for benign adnexal masses
Borderline or low malignant potential
Functional ovarian cyst By far the most common cystic ovarian lesions, among women of reproductive age, are benign functional ovarian cysts. The possibility of dealing with a luteal or follicular cyst must be considered in the presence of irregular periods. Functional cysts include follicular cysts, corpus luteum cysts, and hemorrhagic cysts. Ultrasonographic aspect On ultrasound, follicular cysts present as simple unilocular, round, anechoic cysts with a thin, smooth wall and a maximum diameter of 5 cm. For these types of cysts, even in post menopausal women, the probability of malignancy is extremely low [12]. A corpus luteum cyst has a thick, hyperechoic, and occasionally corrugated wall and usually has hemorragic content. The color Doppler sonography shows a typical vascular ‘ring of fire’ [13]. An hemorrhagic cyst is generally due to expanding hemorrhage within a corpus luteum or other functional cyst. It may evolve into various stages of acute hemorrhage, clot formation, and retraction, thus giving rise to changing sonographic appearances. Hemorrhagic lesion is characterized by the presence of clots, fibrin strands, retracting thrombus, and fluid levels. The internal architecture is responsible for their appearance characterized by low-level echogenic content (‘mesh-like’ or thin ‘cobweb’-like appearance) (Fig. 2) [14]. Management Surgical management of these cysts may not be beneficial in comparison with either medical treatment in the case of a luteal mass or expectant management in cases of a simple
Abscesses, hematomas, lymphoceles Urinomas, bladder diverticulum, ureteral diverticulum, seromas Postpartum complications Subserosal fibroids Congenital malformation of the ipsilateral Mu¨llerian duct Malformation of ipsilateral fallopian tube, round ligament, kidney, or ureter Lobulated accessory supernumerary ovaries Appendiceal abscess or mucocele Pelvic kidney Nerve sheath tumor
Fig. 2 Functional cyst
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The ultrasound-based diagnosis of ovarian endometrioma involved the visualization of persistent round-shaped homogeneous hypoechoic ‘tissue’ with low-level echoes within the ovary. Endometriomas contents may show different patterns ranging from anechoic to solid, depending on the amount of blood and its organization (Fig. 3) [24, 25]. In most cases, endometrioma shows a ‘ground-glass’ pattern, with homogeneously dispersed echogenic cystic content [26].
surgery before in vitro fertilization (IVF)/intra cytoplasmatic sperm injection (ICSI) treatment is considered to be the ‘gold standard’ in symptomatic women with ovarian endometrioma and in asymptomatic patients with endometriomas C4 cm [27]. In any case, the management of ovarian endometriomas in women who desire a pregnancy is still a matter of debate [28, 29]. On one hand, the removal of endometriomas in infertile patients often improves reproductive outcomes, with a reported pregnancy rate after surgery alone of 37.4 % [30]. On the other hand, women undergoing surgery for endometriosis have to cope with both the endometrioma-related injury and the damage caused by surgery [31]. Moreover, as a consequence of cystectomy, ovaries seem to exhibit reduced responsiveness to hyperstimulation with gonadotropins. These effects are clinically more relevant in patients with bilateral endometriomas who undergo surgery more than once [31–37]. The patient should be counseled regarding the risks of reduced ovarian function after surgery and the decision should be reconsidered if she has had previous ovarian surgery [27]. Malignant transformation has been documented in 0.3–0.8 % of patients with ovarian endometriosis [38]. The most frequent histotypes of ovarian cancer deriving from endometriosis are represented by clear-cell adenocarcinoma and endometrioid carcinoma [39].
Management
Dermoid cyst
Management of ovarian endometriomas depends on size of the cyst, previous surgery for endometrioma, associated symptoms, severity of the symptoms, age of the patient, and desire to get pregnant or not. According to the European Society of Human Reproduction and Embryology (ESHRE) guidelines for the diagnosis and treatment of endometriosis, laparoscopic
Ovarian dermoid cyst (mature cystic teratoma) is the most frequent benign ovarian germ cell tumor identified during the adolescent and the reproductive period, comprising 5–25 % of all ovarian masses [40]. It is derived from all three germ cell layers (ectodermal layer, mesodermal and endodermal layer). The ectodermal component is often the most represented [41]. Teratomas vary in size from few millimeters to more than 40 cm; they are usually unilateral but in about 1 in 10 cases may develop in both ovaries.
cyst [15]. According to a Cochrane of 2009 [16], watchful waiting for two or three cycles is appropriate. During the menopause, the majority of simple ovarian cysts resolve spontaneously or persist unaltered on followup. Moreover, these cysts can be followed conservatively because their risk for malignant transformation is low [17]. Ovarian endometrioma Endometriosis is common, with an estimated incidence of approximately 10 % of the general female population [18–21]. Approximately 15–44 % of women with endometriosis have ovarian endometriomas [22, 23]. Ultrasonographic aspect
Ultrasonographic aspect Dermoids have a wide spectrum of sonographic appearances depending on which elements are present. Certain sonographic features occur with a degree of constancy and that allow a confident diagnosis: focal or diffuse hyperechoic components, hyperechoic lines and dots, and area of acoustic shadowing, with no internal flow at color Doppler Ultrasound (Fig. 4) [42, 43]. Management
Fig. 3 Endometrioma
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When surgical management is decided, intraperitoneal leakage of the cystic contents may result in chemical
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Fig. 4 Dermdoid cyst
peritonitis [44, 45]. The reported 15–28 % risk of iatrogenic intraoperative rupture goes far beyond the risk for spontaneous rupture [46]. Malignant transformation of dermoid cysts has been recorded as occurring in 1–2 % of cases. The most common form of malignant transformation is squamous cell carcinoma, which occurs in about 75 % of cases, while adenocarcinoma is rare, with an incidence of 7 % [47]. Hydrosalpinx Hydrosalpinx is characterized by a collection of watery fluid in a uterine tube. It is associated with obliteration of the fimbriae and dilatation of the fallopian tube, in particular the ampullary and infundibular portions. The tube usually contains clear, serous fluid. Ultrasonographic aspect The ultrasound appearance is typical and can be easily distinguished from ovarian abnormalities. It varies according to extension and the stage of the inflammatory process. Frequently the adnexal mass is cystic, tubular, elongated, with incomplete septations. Sometimes the walls present multiple hyperechoic mural nodules (beads-on-astring sign) and/or short linear projections (cogwheel sign) (Fig. 5). In some cases the ovary may also be involved in the disease process to form a chronic tuboovarian mass [11]. Management The presence of hydrosalpinx impairs IVF outcomes by decreasing the implantation and pregnancy rates. The cause of a low pregnancy rate could be due to mechanical, chemical or toxic effects of the tubal fluid. Correction of the hydrosalpinx may improve the outcome of IVF. The
Fig. 5 Paraovarian cyst in menopausal patient
most suitable surgical procedure is still debated. Laparoscopic removal of the hydrosalpinx (salpingectomy) before IVF is the procedure of choice. Other techniques include hysteroscopic proximal tubal occlusion, laparoscopic occlusion of the tube proximally close to the uterus (preferable when the distal fallopian tube is buried in dense and severe adhesions), and transvaginal aspiration of hydrosalpinx. The proper selection of patients for surgical treatment and for the type of surgical technique is essential to achieve good results [48]. Cystadenoma Cystadenoma is very common and may mimic a physiologic cyst. Serous cystadenomas constitute 20 % of all benign ovarian neoplasms and are usually encountered during the reproductive years. In 7–12 % of patients, these tumors are bilateral [11]. Ultrasonographic aspect Their ultrasonographic appearance is similar to functional cysts, except for the fact that they are larger in size and do not go through spontaneous resolution (Fig. 6) [40]. They appear as thin-walled, unilocular or multilocular cysts with anechoic content. The inner lining may be smooth or have areas with grossly visible papillary projections. Septa can be present, but usually they are thin [11]. Mucinous cystadenoma is less common, almost always simple or septate, thin-walled, multilocular, with low-level echoes cystic content, and no solid areas. The size may reach large dimensions, until 40–50 cm [49]. Papillary projections are almost always absent. The content of the single locules may vary depending on the difference in the
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Fig. 6 Peritoneal inclusion cyst Fig. 8 Serous cystadenoma
Ultrasonographic aspect On ultrasonography it appears as a complex mass: unilocular or multilocular, with thick papillary projections. Often solid tissue (nodules) within the mass can be found. In 50 % of the cystadenofibroma, intracystic blood flow is seen, from slight to moderate [50] (Fig. 8). Ectopic pregnancy
Fig. 7 Hydrosalpinx
chemical composition of fluids, rather than the difference in viscosity. The sonographic detection of variable echogenicity in the contents of an adnexal multilocular cyst is strongly suggestive of a mucinous tumor (Fig. 7) [11]. Management Preoperative knowledge of the mucinous nature of the tumor is of crucial importance to prevent spillage. The occurrence of spillage of mucin may cause spread of cells in malignant tumors and Pseudomyxoma peritonei. This is a rare clinical entity characterized by diffuse intraabdominal gelatinous collections with mucinous implants on the peritoneal surfaces and omentum [49]. Cystadenofibroma Some authors consider cystadenofibromas a variant of serous cystadenomas. They are found in patients aged 15–65 years (mean 30.7 years) and constitute nearly half of all benign ovarian cystic serous tumors.
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Ectopic pregnancy is defined as a pregnancy implanted outside of uterine cavity [51, 52]. Approximately 1–2 % of all pregnancies in Europe and the USA are ectopic. In the Western world tubal ectopic pregnancy remains the most common cause of maternal mortality in the first trimester of pregnancy [52, 53]. Ultrasonographic aspect At Ultrasound, the extra-uterine gestational sac with trophoblastic tissue might appear as an extra-ovarian thickwalled adnexal mass (the tubal ring sign) [11] (Fig. 9). Up to 20 % of patients with ectopic pregnancy demonstrate an intrauterine pseudogestational sac. Parovarian and paratubal cyst Parovarian and paratubal cysts may arise from mesonephric (Wolffian) structures, paramesonephric (Mu¨llerian) structures, or mesothelial inclusions [11]. Ultrasonographic aspect Their sonographic appearance is characterized by thin, regular walls and anechoic content, that are not surrounded
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Fig. 9 Large mucinous cystadenoma
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Fig. 11 Ectopic pregnancy
level echoes due to hemorrhagic or proteinaceous fluid [11]. Differential diagnosis includes parovarian cysts and hydrosalpinx [54, 55] (Fig. 11). Ultrasonography of the adnexa: two-dimensional, Doppler, three-dimensional (3D) and real-time four-dimensional (4D)
Fig. 10 Cystadenofibroma
by ovarian stroma. Hormonal cycle does not affect their size. The most common paramesonephric cyst is the hydatid of Morgagni (Fig. 10). Peritoneal inclusion cyst Peritoneal inclusion cysts occur mainly in women with a history of previous abdominal surgery, pelvic inflammatory disease or endometriosis. In patients with peritoneal adhesions, fluid collections can create cysts of various shapes. Fluid may entrap the ovaries with or without ovarian cysts, resulting in a large adnexal mass. Ultrasonographic aspect Sonographically they appear as extra-ovarian, multilocular pelvic cysts, with regular wall and irregular shape. The content is usually anechoic; sometimes it contains low-
Transvaginal or transabdominal ultrasound examination is recommended as part of the initial workup of an adnexal/ ovarian mass [56]. Despite advances in technology, conventional gray-scale transvaginal sonography (TVS) remains the most common imaging modality for the evaluation of adnexal masses. Through the use of high-frequency probes it allows a detailed morphologic view. The use of Doppler analysis for the purposes of colorflow mapping and characterization of waveforms was to evaluate neovascularity of ovarian neoplasms. The addition of Doppler techniques appears to offer improved specificity in the diagnosis of adnexal masses over two-dimensional ultrasonography. Doppler imaging includes color-flow morphology, pulsed Doppler, power Doppler, and power Doppler angiography [1]. The resistance index, the pulsatility index, and the maximum systolic velocity are parameters that objectively quantify vessel flow characteristics to distinguish high- and low-resistance vessels. The IOTA Group suggested the use of a subjective semiquantitative assessment of flow to describe the vascular features of adnexal masses [26]. Malignant lesions usually produce a significant increase in color Doppler flow signals secondary to angiogenesis not only at the periphery but also in the central regions of the mass, including septa and solid areas [57]. However, because of the overlap of flow characteristics among benign, borderline, and malignant neoplasms, a firm differential diagnosis based on Doppler evaluation alone is not possible [1].
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Fig. 12 Three-dimensional ultrasonography
The availability of three-dimensional (3D) and real-time four-dimensional (4D) ultrasound has provided a new way of studying adnexal masses (Fig. 12). The system offers several analysis tools, such as multiplanar imaging, surface and volume rendering, semi-automated volume calculation and quantification of echogenicity of the adnexal mass [11]. Moreover, three-dimensional ultrasound allows the off-line assessment of stored 3D/4D volumes. Three-dimensional power Doppler examination offers the possibility to visualize and quantify blood flow in adnexal masses. Recently Perez observed that 3D-power Doppler angiography values increase progressively, but not significantly, with the stage of malignancy in complex ovarian masses [58]. Accuracy of ultrasonography and scoring systems In the hands of an experienced ultrasound examiner, the socalled ‘pattern recognition’, that is the subjective evaluation of ultrasound findings, is an excellent method for discrimination between benign and malignant masses. A multi-centre prospective trial (IOTA) concluded that pattern recognition of ultrasound images by a trained observer was superior to serum Ca-125 for discrimination between benign and malignant adnexal masses [59]. Sokalska et al. [60] examined the sensitivity and specificity of subjective evaluation of gray-scale and Doppler ultrasound findings when applied by experienced ultrasound examiners. The study was realized within the
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framework of the IOTA study and included a total of 1,066 women, of whom 800 had a benign mass and 266 had a malignant mass. A specific diagnosis based on ultrasound findings was suggested in 899 (84 %) tumors. The specificity was high for all diagnoses (94–100 %). The sensitivity was highest for benign teratoma/dermoid cysts (86 %), hydrosalpinges (86 %), peritoneal pseudocysts (80 %) and endometriomas (77 %), and lowest for functional cysts (17 %), paraovarian/parasalpingeal cysts (14 %), benign rare tumors (11 %), adenofibromas (8 %), simple cysts (6 %) and struma ovarii (0/5). The positive and negative likelihood ratios with regard to dermoid cysts, hydrosalpinges and endometriomas were 68.2 and 0.14, 38.9 and 0.15, and 33.3 and 0.24, respectively. The authors concluded that using subjective evaluation of gray-scale and Doppler ultrasound findings it is possible to make an almost conclusive diagnosis of a dermoid cyst, endometrioma and hydrosalpinx. Many other adnexal pathologies can be recognized but not confidently confirmed or excluded. Initial reports on 3D ultrasonography suggest a possible improved performance compared to 2D ultrasonography. 3D ultrasonography showed sensitivities ranging from 78 to 100 %, specificities from 78 to 92 % and negative predictive values of 95–99 % in the identification of malignancy among women with an adnexal mass. Further studies are required to assess whether 3D sonography may be appropriate in the triage of the intermediate-risk adnexal mass identified by two-dimensional imaging [1].
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Accuracy of pelvic ultrasonography and image quality are both equipment- and operator-dependent. It is important to be aware that studies reporting on the accuracy of ultrasonography in discriminating benign from malignant adnexal masses are typically undertaken under optimal conditions, using contemporary high-resolution equipment with a limited number of experts performing and interpreting the scans. To overcome some of the subjective elements of interpretation and improve reproducibility, a variety of predictive models with the use of scoring systems, logistic regression analysis, neural networks, and support vector machines have been developed to increase the accuracy of the preoperative assessment of the adnexal mass. The three most commonly used and validated indexes are Sassone scoring system [61], Ovarian Tumor Index (OTI) [62], and the risk of malignancy index (RMI), recommended by the Royal College of Obstetricians and Gynaecologists [5]. Unfortunately, when these models were tested prospectively, they performed less well than was originally reported [63–68]. IOTA and simple rules The IOTA study group developed two logistic regression models that performed as well in new centers as in the units where the models were first developed [69]. However, no model or biochemical marker of ovarian malignancy has been shown to be superior to subjective assessment of gray-scale and color Doppler ultrasonic findings by an experienced ultrasound examiner. The expertise of experienced ultrasound examiners is not easily transferred to less experienced examiners. Therefore, proper teaching and training in ultrasonography remain essential [70]. The simple ultrasound rules proposed by the IOTA group to discriminate between benign and malignant adnexal masses seem more generalizable. This method is based on five ultrasonic features to predict a malignant tumor (M features): irregular solid tumor (M1), ascites (M2), at least four papillary structures (M3), irregular multilocular solid tumor with a largest diameter of at least 100 mm (M4), and very high color content on color Doppler examination (M5). Five ultrasonic features were adopted to predict a benign tumor (B features): unilocular cyst (B1), presence of solid components for which the largest solid component is \7 mm in largest diameter (B2), acoustic shadows (B3), smooth multilocular tumor (B4), and no detectable blood flow on Doppler examination (B5). If one or more M features were present in the absence of a B feature, we classified the mass as malignant (rule 1). If one or more B features were present in the absence of an M feature, we
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classified the mass as benign (rule 2). If both M features and B features were present, or if none of the features was present, the simple rules were inconclusive (rule 3) [71]. A study observed that the rules reliably discriminated between benign and malignant adnexal masses. They did so just as well as subjective assessment by an experienced ultrasound examiner did [72]. We should observe that, to increase the specificity of ultrasound, reproducible and accurate method for the sonographic evaluation of ovarian masses must be implemented. This moved to improve and standardize reporting in gynecological ultrasound. In light of this, the IOTA study group provided a reproducible standardized methodology to describe adnexal pathology when performing transvaginal ultrasound [26]. A standard reporting in gynecological ultrasound may develop into a very promising tool to produce a common language for scientific groups studying adnexal masses and thus to allow comparisons of results. Role of second-level exam Nevertheless, even in the most experienced hands, 10 % of adnexal masses are still difficult to classify on TVS [6]. According to Timmerman et al. [72] for tumors that cannot be classified using simple rules, ultrasound examination by an expert examiner might be useful. The clinical practice guideline by Dodje et al. [73] confirmed that TVS should be the modality of first choice in patients with a suspicious isolated ovarian mass. To help clarify malignant potential in patients in whom ultrasonography may be unreliable, magnetic resonance imaging (MRI) is the most appropriate test. In cases in which extraovarian disease is suspected or needs to be ruled out, computed tomography (CT) is the most useful technique. Secondary testing may include also CA125, other biomarkers combinations and Proteomics [73, 74]. The CA 125 is the most extensively investigated serum marker for ovarian cancer. Elevated serum CA125 has been reported in a variety of benign conditions. Moreover, serum CA125 is elevated in only 50 % of early-stage ovarian cancers [73]. As such, it has a low specificity, especially in premenopausal women [75–77]. To increase specificity of Ca125 for detecting ovarian carcinoma, a variety of serum proteins have been identified. Proteomic technology has been investigated to determine if serum protein profiling patterns could be used to distinguish between benign and malignant adnexal masses [1]. In September 2009, the Food and Drug Administration approved a serum-based test called OVA1 for the presurgical evaluation of a woman with an ovarian mass. The test combines five separate serum protein marker
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(Beta-2 microglobulin, CA 125, apolipoprotein A1, Prealbumin and Transferrin) results as well as menopausal status into a single numerical score between 0 and 10 to indicate the likelihood that the pelvic mass is benign or malignant. It is important to emphasize that neither serum biomarkers nor more complex tests can replace clinical judgment and further confirmatory studies are underway [1].
(c)
6.
7. Conclusion Ultrasound represents the first-line modality for assessing adnexal masses. Predicting the nature of an adnexal mass is essential regarding counseling, clinical management and surgical planning in such patients. Pattern recognition can accurately diagnose some of the benign masses and malignancies. However, the sonographic appearance of an ovarian mass is not pathognomonic in 10 % of adnexal masses. In these indeterminate cases a second-level exam may be beneficial. Patient’s age, symptoms, features of menstrual periods, and family history should always be taken into consideration when evaluating an adnexal mass. Crucial points 1.
2.
3.
4. 5.
Transvaginal ultrasound showed a very accurate examination, but it is highly operator and equipment dependent; The primary goal of ultrasonographic evaluation of adnexal masses is to exclude malignancy; adnexal masses with ultrasonographic features suggestive of malignancy should be referred to gynecologic oncologists; Differentiation among the different pelvic masses with benign features is relevant as well since suitable counseling and treatment depend on the suspected histology; Second-level exams may include assessment by an experienced ultrasound examiner, MRI, and CT; Using subjective evaluation based on gray-scale and color or power Doppler features, endometriomas, dermoid cysts, and hydrosalpinges can be correctly categorized: (a)
(b)
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Endometrioma’s sonographic features: persistent round-shaped homogeneous hypoechoic cyst with low-level echoes within the ovary, internal homogeneous ground-glass or low-level echoes, without internal color Doppler flow; Dermoid’s sonographic features: focal or diffuse hyperechoic components, hyperechoic lines and dots, and area of acoustic shadowing, with no internal flow at color Doppler Ultrasound;
Hydrosalpinx sonographic features: tubular, elongated, with incomplete septations. Sometimes multiple hyperechoic mural nodules (beads-on-a-string sign), and/or short linear projections (cogwheel sign);
Doppler technique, 3D and 4D ultrasonography appears to improve specificity in the diagnosis of adnexal masses; No model or biochemical marker of ovarian malignancy has been shown to be superior to subjective assessment of gray-scale and color Doppler ultrasonography.
Conflict of interest interest to report.
None of the authors have financial conflicts of
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