Neoplasms of the Ovary

Abstract

Adnexal masses (AMs) are common findings among both premenopausal and postmenopausal women. The main goals of an initial diagnostic work-up for an AM are to rule out malignancy and to differentiate between AM requiring surgical intervention and those that can be managed conservatively. Among the gynecological sources, diagnostic entities can be broadly separated into functional or physiological, inflammatory, or neoplastic lesions. The latter category can be split into the following sub-categories: epithelial–stromal tumors, sex cord–stromal tumors, germ cell tumors, and secondary tumors. It is also crucial to consider the clinical context of each individual patient diagnosed with an AM. Multimodality imaging assessment plays a key role in the management of adnexal masses and helps to plan the most appropriate therapeutic approach.

The following parameters should be assessed by imaging preoperatively: exact origin of the mass, characterization, likelihood of malignancy, and, when surgery is needed, the feasibility of laparoscopy versus laparotomy.

Transabdominal and transvaginal ultrasonography (TVUS) represent the first-line imaging technique currently used to evaluate AM. Computed tomography (CT) is commonly performed in preoperative disease assessment of a suspected ovarian malignancy.

Magnetic resonance (MR) imaging is now widely accepted as the “problem-solving technique” for the characterization of an indeterminate AM having both high sensitivity and specificity in discriminating benign versus malignant lesions.

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6.1 Introduction

6.1.1 Anatomy and Pathology

Ovaries are paired nodular structures located laterally to the uterus in relation to the lateral pelvic wall. They are the female reproductive internal organs and can produce gonadal cells and secrete hormones – mainly estrogen and progesterone. Their exact localization is highly variable, but they are typically found below the bifurcation of the common iliac vessels lateral to the uterine cornua. Histologically, the ovaries consist of several vesicular follicles embedded within a mixed connective tissue and spindle cell stroma. An adnexal mass is an enlarged structure in the uterine adnexa that can be palpated on bimanual pelvic examination or visualized with diagnostic imaging techniques [1, 2]. Adnexal masses are common findings among both premenopausal and postmenopausal women – nearly 10 % of women will undergo surgical evaluation for an adnexal mass or a suspected ovarian neoplasm at some point in their life [1, 2]. The majority of adnexal masses in the overall population are benign, with a small percentage of patients harboring an ovarian malignancy. The main goals of an initial diagnostic work-up for an adnexal mass are to rule out malignancy and to differentiate between adnexal masses requiring surgical intervention and those that can be managed conservatively. The differential diagnosis of an adnexal mass includes both gynecological and non-gynecological entities. Among the gynecological sources, diagnostic entities can be broadly separated into functional or physiological lesions, inflammatory lesions, or neoplastic lesions (Table 6.1) [3].

Table 6.1 The most common etiologies of adnexal mass

The latter category can be split into the following sub-categories:

• (a) Surface epithelial–stromal tumors

• (b) Sex cord–stromal tumors

• (c) Germ cell tumors

• (d) Secondary (metastatic) tumors

These latter are also important as treatment options differ from those for primary ovarian malignancies.

Overall, it is widely accepted that if an adnexal mass is considered to have an appreciable risk of malignancy, surgery should be recommended. It is nevertheless crucial to consider the clinical context of each individual patient diagnosed with an adnexal mass when determining the most appropriate diagnostic and therapeutic strategy. Partly because of the low incidence of ovarian cancer in the general population, there are no accepted effective screening tests to early identify women with ovarian cancer [4] – unless there is a strong family history or a known gene mutation (e.g., BRCA).

There are three main clinical routes by which an adnexal mass may be detected: (1) symptomatic women diagnosed with an adnexal mass by physical exam or imaging, (2) adnexal mass detected during bimanual pelvic examination, and (3) asymptomatic adnexal mass detected incidentally on imaging performed for another indication [2].

In premenopausal women, the most likely scenario is an ultrasound evaluation during the pregnancy – even though the incidence of a malignancy is rare in this case. In peri- or postmenopausal women, the most common scenario would be while performing an evaluation for pelvic–vaginal (PV) bleeding. Since PV bleeding is not a common symptom of ovarian cancer, an adnexal mass found during evaluation for bleeding is an incidental finding [2].

6.1.2 Imaging

Multimodality imaging assessment plays a key role in the management of adnexal masses. Imaging helps to plan the most appropriate therapeutic approach. Since benign ovarian lesions are nowadays treated with laparoscopy, pretreatment imaging findings associated with proper characterization of an ovarian lesion are crucial [5]. The following parameters should be assessed by imaging preoperatively: (a) exact origin of the mass, (b) likelihood of malignancy, and (c), when surgery is needed, the feasibility of laparoscopy versus laparotomy [6].

Transabdominal and transvaginal ultrasonography (TVUS) represents the first-line imaging technique currently used to evaluate ovarian masses [7]. TVUS has been the foremost modality for detection and characterization of ovarian tumors. Especially with the advent of high-frequency transvaginal probes, the quality of images allows description of the lesion’s gross anatomical features, hence making TVUS the method of choice in studying ovarian lesions. This is, however, limited by the great variability of macroscopic characteristics of both benign and malignant masses. Furthermore, the technique is operator dependent. To overcome these limitations, morphological scoring systems have been developed – this being based on specific ultrasound parameters each with several scores according to determined imaging features of the lesion and clinical data. The color Doppler scanning allows the assessment of tumor vascularity. Overall, malignancies display an increased vascularity with decreased peripheral blood flow resistance and increased blood flow velocity compared with benign tissue [2, 8–10]. Nevertheless, a significant proportion of adnexal masses (up to 20 %) remain indeterminate after TVUS.

Magnetic resonance (MR) imaging is now widely accepted as the “problem-solving technique” for the characterization of an indeterminate ovarian mass having both high sensitivity and specificity in discriminating benign versus malignant lesions. Moreover, thanks to its exquisite soft tissue contrast definition, it can address specific diagnosis for certain pathological types [7] (e.g., teratomas, endometriomas).

Computed tomography is commonly performed in preoperative disease burden assessment of a suspected ovarian malignancy [11–13].

6.1.2.1 MRI Assessment of an Adnexal Mass

6.1.2.1.1 Patient Preparation and Coil Selection for MRI Assessment

Patients undergoing MRI examination should have fasted for at least 4 h to limit artifacts due to bowel peristalsis. Further reduction of motion artifacts can be achieved with the use of antiperistaltic agents. Imaging is performed with the patient in supine position using a multichannel phase array coil. Endorectal and endovaginal coils have a limited field of view for the assessment of lateral pelvic structures and are therefore not routinely used.

6.1.2.1.2 Conventional MRI Sequences

A typical imaging protocol includes T1-weighted images (T1WI) in the axial plane and T2-weighted images (T2WI) in the axial, sagittal, and coronal planes using a small field of view (20 cm), a high resolution matrix (e.g., 256 × 256), and thin section images (3 mm). Fat-saturated T1-weighted images (T1W FS) are used to evaluate the presence of fat or hemorrhage, especially when high signal intensity is seen within the adnexa on T1WI and a dermoid tumor or endometriosis is suspected. In patients undergoing ovarian cancer staging, axial T1WI or fast spin-echo T2WI with a large field of view up to the renal pelvis should be included to evaluate the presence of metastatic disease (e.g., lymph node, liver, or bone metastases).

6.1.2.1.3 Contrast-Enhanced MRI Sequences

Gadolinium-enhanced images are useful for the evaluation of complex lesions as they may help differentiating solid components or papillary projections from clots and debris. Multiphase contrast-enhanced MRI is performed by using a three-dimensional gradient echo T1-weighted sequence after administration of 0.1 mmol gadolinium per kg of body weight. Dynamic contrast-enhanced MRI (DCE-MRI) involves repeatedly imaging a predetermined volume of interest every few seconds over 5–10 min during the passage of the contrast agent through the tissue of interest, so that changes in signal intensity can be assessed as a function of time. Semi-quantitative analysis can be performed through several parameters derived from contrast enhancement/time curves.

6.1.2.1.4 Diffusion-Weighted MRI (DW-MRI)

DW-MRI is performed using two or more b-values, which include one or more low b-values (50–100 s/mm²) and a high b-value (750–1,000 s/mm²). The apparent diffusion coefficient (ADC) is measured in mm²/s and is calculated by the slope of the line of the natural logarithm of signal intensity versus b-values. The ADC maps are usually displayed as gray-scale images. Areas of restricted diffusion have lower ADC values and appear as a darker shade of gray on the ADC maps compared with areas of freely moving water such as cysts or bladder, which appear as a lighter shade of gray. Areas of restricted diffusion appear bright in the high-b-value images (b-value 750–1,000 s/mm²).

6.1.2.1.5 Role of MRI in Characterizing Ovarian Masses

The greatest strength of MRI lies in its ability to characterize the physical and biochemical properties of different tissues (e.g., water, iron, fat, and extravascular blood and its breakdown products) through the use of multiple imaging sequences. There are no MRI signal intensity characteristics that are specific for malignant epithelial tumor, and these tumors should be distinguished based on morphologic criteria. The MRI features most predictive of malignancy are an enhancing solid component or vegetations within a cystic lesion, presence of necrosis within a solid lesion, as well as presence of ascites and peritoneal deposits [14, 15].

6.1.3 Defining the Origin of a Pelvic Mass: Adnexal, Extra-adnexal, and Extraperitoneal

Defining the correct origin of a mass is the first diagnostic step in setting up a treatment strategy. The size, architecture, and location may appear similar in adnexal, extra-adnexal peritoneal masses and even in extraperitoneal lesions. However, special features determining the anatomical relationship of the mass and the surrounding pelvic anatomical structures can help in their differentiation [16]. These parameters include visualization of ovarian structures, the type of contour deformity at the interface between the ovary and the pelvic mass, and the displacement pattern of the vessels, ureters, and other pelvic organs. Particularly in large pelvic lesions, the ovary may often be obscured or totally invaded by the mass [8]. In smaller lesions, when the ovary is not completely obscured, identifying ovarian structures – such as follicles – indicates its ovarian origin. Specific signs such as the “beak” sign and the “embedded organ” sign can aid in better defining the mass relationship with the ovary. When a mass deforms the edge of the ovary into a beak shape, it is likely arising from the ovary. In contrast, dull edges at the interface with the adjacent ovary suggest that the tumor compresses the ovary but does not arise from this [16]. Large ovarian masses typically displace the ureter posteriorly or posterolaterally. However other intraperitoneal lesions (e.g., those originating from the bladder, the uterus, or the bowel) can cause the same pattern of displacement [17]. An adnexal lesion typically displaces iliac vessels laterally. In contrast, extraovarian masses arising from the pelvic wall or lymphadenopathies displace the iliac vessels medially. The mass origin may be further elucidated by tracking the vascular pedicle or the ovarian suspensory ligament [16]. Because of their close anatomical relationship, masses arising from the fallopian tubes often cannot be distinguished from ovarian ones. However, incomplete septa emerging from the wall of a cystic “sausage-like” adnexal mass indicate its fallopian origin [18].

6.1.4 Differentiating Benign from Malignant Lesions

The clinical significance of discriminating benign from malignant masses differs depending on the clinical setting in which the mass is initially detected. For women with symptoms, in whom surgical management may be appropriate whether or not the mass is malignant, the main reason to discriminate between benign and malignant lesions is to set up the correct management. For asymptomatic women, discriminating benign from malignant disease is important both to ensure appropriate management in the setting of malignancy and to avoid unnecessary diagnostic procedures, including surgery.

Several MR imaging findings suggestive of malignancy have been reported in the literature. These can be summarized as follows: complex solid–cystic appearance, presence of wall irregularity and thickening, multiple (>5) septations with nodularity, and vegetations and solid enhancing components after contrast medium administration [19]. Predominantly cystic appearance with thin wall and septa and presence of strong hypointensity on T2-weighted images are more often associated with benign lesions. Secondary features of malignancy representing disease involvement of surrounding/distant structures consist of peritoneal, mesenteric, or omental deposits, pelvic side wall invasion, and lymphadenopathy, although pelvic ascites can also be seen in ovarian torsion, pelvic inflammatory disease, and benign ovarian fibroma [3, 4]. When these criteria are applied, the method sensitivity in detecting malignancy is 91–100 % and the specificity is 91–92 % [19, 20]. More recently, functional MRI techniques such as diffusion-weighted MRI (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) have demonstrated a valid contribution in ovarian masses’ characterization. DW-MRI indirectly informs about tumor cellularity and tumor membrane integrity via apparent diffusion coefficient (ADC) calculation. The ADC value has been reported as useful in discriminating between benign and malignant ovarian surface epithelial tumors [20], although there is still no evidence that DW-MRI can independently characterize an ovarian mass [21–25]. DCE-MRI characterizes the leakage of contrast agent from capillaries into the extravascular extracellular space allowing quantitative measurements that reflect blood flow and vascular permeability. Quantitative DCE-MRI parameters have been shown to correlate to tumor angiogenesis status [26]. Semi-quantitative DCE-MRI parameters and curve analyses have also demonstrated a role in predicting malignancy with an increased specificity compared with conventional MRI [27]. Specifically a relationship between early enhancement of solid tumor components and malignancy has been postulated [5, 28, 29].

The probability of malignancy is also related to the patient’s age. In young women less than 9 years of age, 80 % of ovarian masses are malignant, with the vast majority consisting of germ cell tumors. In women of reproductive age, the overall chance that an ovarian tumor will be malignant is 1 in 15 compared to 1 in 3 by 45 years of age [30].

6.1.4.1 Low-Risk Adnexal Masses

If both pre-assessment probability and imaging studies demonstrate low probability of malignancy, additional tests can be avoided [3].

6.1.4.2 Intermediate-Risk Adnexal Masses

The most challenging decision-making cases are the ones with intermediate risk for malignancy. A large proportion of intermediate-risk adnexal masses represent benign entities. Tests with greater specificity allow point-of-care triage that may obviate the need for surgery that would otherwise be purely for diagnostic purposes. However, in case of malignancy they would potentially offer a more timely diagnosis than a “watch and wait” strategy with interval ultrasound reassessment [3]. Tumor markers such as CA125 may be selectively performed, particularly in the postmenopausal population in which specificity is higher. Alternatively, surgical evaluation can be considered if the perceived risk for malignancy justifies this intervention [3].

6.1.4.3 High-Risk Adnexal Masses

If there is sufficiently high risk, then additional diagnostic studies may not be necessary, and clinicians may wish to proceed with studies most relevant to surgical planning and gyne-oncology referral [3].

6.1.5 Ovarian Tumors by Morphologic Characteristics

Morphological characteristics of adnexal masses provide important information for determining the pathological group of a tumor. Although MR imaging findings are not specific for any particular pathological group, some imaging features are more characteristic of one pathological group than another. Ovarian tumors are usually classified into three groups: cystic masses (unilocular or multilocular), cystic and solid masses, and predominantly solid masses.

6.1.5.1 Cystic Masses

Cystic masses may include nonneoplastic cysts, benign neoplasms, and borderline neoplasms. Functional cysts, para-ovarian cysts, hydrosalpinx, endometriotic cysts, serous cystadenomas, mucinous cystadenomas, and mucinous cystic tumors of borderline malignancy are the ovarian cystic lesions most frequently found.

6.1.5.2 Cystic and Solid Masses

In general, a combined cystic and solid mass strongly supports the diagnosis of ovarian malignancy. Primary epithelial carcinomas and metastatic tumors often show a cystic and solid appearance. Mature cystic teratoma is the important exception to this appearance.

6.1.5.3 Solid Masses

Predominantly solid ovarian masses include benign, borderline, and malignant tumors. The main entities are fibrothecomas, Brenner tumors, granulosa cell tumors, dysgerminomas, epithelial ovarian carcinomas, and metastatic carcinomas.

6.2 Benign Ovarian Lesions

Benign adnexal lesions constitute about 80 % of all ovarian tumors. They mostly occur in young women (<45 years). As for malignant tumors, benign neoplasms arise from one of the three ovarian components: surface epithelium, germ cells, or sex cord–stroma [31].

6.2.1 Physiologic Ovarian Cysts

Ovarian cysts below 3 cm are generally considered physiological. These entities can be divided into functional (associated with hormone production) or nonfunctional [32]. Functional cysts comprise follicular cysts, corpus luteum cysts, and uncommon cysts such as the theca–lutein cysts [33] (Fig. 6.1). Simple cysts are thin-walled (<3 mm), unilocular, and below 3 cm in diameter, but can occasionally grow larger. They usually develop during reproductive age, but may also be found in postmenopausal age and are almost always asymptomatic. The majority are follicular cysts and result from failure of rupture or of regression of the Graafian follicle. They are usually self-limiting and usually regress spontaneously within 2 months. Sometimes they are complicated by rupture and may cause abdominal pain and hemoperitoneum [7]. Most functional cysts appear as unilocular small cystic lesions with high signal intensity on T2-weighted images and intermediate to low signal intensity on T1-weighted images, reflecting simple fluid content. Hemorrhagic cysts usually present high signal on T1-weighted images [10, 34]. The thin wall of functional cysts is best depicted on T2-weighted images as a hypointense structure and on contrast-enhanced images as hypervascular in respect to ovarian stroma [11, 35, 36]. When below 3 cm of diameter, they cannot be differentiated from mature follicles. Unilocular cystadenomas may mimic functional cysts, but a follow-up that shows regression over 2–3 ovarian cycles allow the diagnosis of functional cyst. Corpus luteum cysts may get bigger in size because of internal hemorrhage [2, 37, 38]. Hemorrhagic and corpus luteum cysts usually have thicker walls with relatively higher signal intensity on T1-weighted images and intermediate to high signal intensity on T2-weighted images [11]. Among nonpregnant women, corpus luteum cysts derive from failure of regression or hemorrhage into the corpus luteum [2]. Theca–lutein cysts develop when choriogonadotropin levels are abnormally increased – e.g., in the gestational trophoblastic disease or in the ovarian hyperstimulation syndrome [31, 39]. Progesterone production may persist in corpus luteum cysts, therefore resulting in dysmenorrhea. When these cysts are large in size, they can cause abdominal pain because of rupture, hemorrhage, or torsion. Corpus luteum cysts often require indeed up to 3 months to regress [2, 7]. Both corpus luteum cysts and endometriomas may show hemorrhagic content; however, a prominent T2 shading can be observed only in endometriomas, while corpus luteum cysts contain less concentrated hemoglobin, so the T2 shading is less common [32, 40]. Internal debris and fibrin clots can be differentiated from papillary projections of epithelial tumors by their lack of enhancement [32].

Fig. 6.1

Inclusion cyst. Follow-up scan in a 44-year-old woman with history of endometriosis. Sagittal and axial spin-echo T2-weighted images (TR:4361, TE:80; a, b): right-sided pelvic collection containing the right ovary anteriorly (arrows). There are no suspicious solid components

6.2.2 Endometriomas

External endometriosis is defined as the condition in which endometrial tissue is found in extrauterine sites [40, 41]. Endometrioid cysts, or endometriomas, are benign entities that can reach fairly large dimensions [40]. Malignant transformation is a rare complication (less than 1 %), and the most common histological subtypes include endometrioid and clear cell carcinoma [42].

External endometriosis mainly affects ovaries [41] and bilateral ovarian involvement occurs in 30–50 % of patients [43]. Endometriomas contain an obliterated loculus, lined by endometrial glands [44, 45]. These lesions range from cystic to solid appearance, depending on cyclic modifications under hormonal stimulation – likewise the normal endometrium. As a result, endometriomas may enlarge [7] and their walls can become fibrotic and thickened and may present an irregular external border [46]. These aspects have been explained with the attitude of endometrial loculi to perforate, producing a severe fibrosis as a result of the irritating effect of blood, with subsequent adhesion to the surrounding structures. Another hypothesis is that endometrial cysts have a free exit to the peritoneal cavity and are necessarily sealed off by organized blood or adhesions to surrounding organs [7]. Malignant transformation is a rare complication (less than 1 %); the most common histological subtypes include endometrioid and clear cell carcinoma [42, 47].

On MRI endometriomas usually present as multiple hemorrhagic cysts [34, 48–50]. They have an iron concentration many times higher than even the whole blood [51–53], and this characteristic gives them their typical very high signal intensity on T1-weighted fat-suppressed images and low signal intensity on T2-weighted images [54]. Homogeneous T2 shading, defined as signal loss on T2-weighted images [55], is a characteristic feature of endometriomas, and it mainly depends on their age and the amount of hemosiderin [56]. Other MRI findings include: adhesion to surrounding organs, a distinct low-intensity zone surrounding a cyst loculus on both T1- and T2-weighted images (thick fibrous capsule), loculus content with short T1 and T2 values (recent hemorrhagic content), dependent layering and a T2-hypointense fluid level representing different-aged blood products, and a hypointense peripheral ring caused by hemosiderin staining in chronic lesions [7, 34]. Non-cystic endometriomas may be difficult to identify due to their small size. Nevertheless, these implants are obviously more evident on fat-saturated T1-weighted images and show low signal intensity on T2-weighted images due to fibrosis surrounding glandular islands [57–60]. DW imaging may aid in differentiation between clots and clear cell cancer development within almost-solid endometriomas [48, 60, 61].

6.2.3 Cystadenomas

Cystadenomas are common epithelial ovarian tumors. Two main histological cystadenomas subtypes have been identified: serous and mucinous [33]. Although an overlap exists, imaging features may aid in the differentiation of serous from mucinous cystadenomas [5].

They account for 40–50 % of benign ovarian tumors in the reproductive age, with an increasing frequency with age, so that after menopause cystadenomas account for up to 80 % of the benign ovarian tumors [5, 32]. Cystadenomas are thin-walled unilocular or multilocular cystic lesions filled with serous or mucinous content, sometimes showing hemorrhagic content [22]. Papillary projections within cystic walls are rarely found; therefore, these findings should raise the suspicion of malignancy [22, 62, 63]. Serous and mucinous cystadenomas differ in pathology and prognosis. Serous cystadenomas account for 20–40 % of all benign ovarian neoplasms, with a peak incidence in the 4th to 5th decade of life, and up to 20 % of them are bilateral. They are often unilocular and the inner lining may be smooth or have gross papillary projections [5, 33, 64] (Fig. 6.2). Mucinous cystadenomas account for 20–25 % of benign ovarian neoplasms. They are more common during the 3rd to 5th decade of life and are bilateral in only 2–5 % of cases. They tend to be larger at the time of presentation and are more frequently multilocular, with different contents of the loculi. Mucinous cystadenomas are lined by a single layer of tall, columnar epithelial cells and contain a sticky gelatinous fluid; rupture of a mucinous cystadenoma can result in pseudomyxoma peritonei [5, 22, 25]. At MRI serous cystadenomas have simple fluid signal and hypointense on T1- and hyperintense on T2-weighted images. In contrast, mucinous cystadenomas have often various signal intensities depending on the content of different loculi, varying from simple fluid to proteinaceous to hemorrhagic. Mucin has lower intensity than serum on T2-weighted images. Rarely, mucinous cystadenoma can present as a simple cyst [5].

Fig. 6.2

Benign serous cystadenoma. A 32-year-old woman with a right adnexal cystic lesion showing thin septa on the right wall (arrow). The largest component shows high signal on T1-weighted (TR:519, TE:10; a) and T2-weighted imaging (TR:4361, TE:80; b) suggestive of hemorrhagic and/or proteinaceous contents. The remainder of the complex lesion shows low signal on T1-weighted imaging (TR:519, TE:10) and high on T2-weighted imaging (TR:4361, TE:80). There is no significant enhancement following gadolinium (axial and sagittal T1 fat-sat imaging, TR:519, TE:10; c, d). No pathological areas of restricted diffusion (b = 1,000 imaging, e; corresponding ADC map, f)

6.2.4 Adenofibroma and Cystadenofibroma

Adenofibromas and cystadenofibromas are classified as surface epithelial–stromal tumors. They represent about half of all benign ovarian cystic serous tumors and are usually found in women aged 15–65 years [65]. Imaging features are nonspecific and may be similar to malignant or borderline tumors [66]. In fact, the variable amount of fibrous stroma determines various aspects, from oligocystic to complex cystic with solid components or even totally solid, that can mimic ovarian cancer [22, 67]. Almost half of the patients with cystadenofibroma have an abnormal contralateral ovary [68]. Adenofibromas and cystadenofibromas are histologically characterized by fibrous tissue components with epithelial elements, similar to those of ovarian cystadenomas. They can also be completely cystic, with microscopic stromal foci, and their margins are usually well defined and smooth [22, 59, 69]. A black spongelike appearance on T2-weighted images is characteristic of these tumors, consisting of tiny high T2 signal intensity foci within very hypointense solid components, reflecting small cystic glandular structures within a dense fibrous stroma [60]. The majority of solid components shows very low T2 signal intensity and minimal enhancement [5, 6, 33, 60, 70]. Low signal intensity and diffusely or partially thickened cystic wall on T2-weighted images are features suggestive of cystadenofibroma [62] (Fig. 6.3). On DW images, the majority of fibromas and fibrothecomas show both low signal intensity on high-b-value images and low corresponding ADC values (mean 1.156 × 10⁻³ mm²/s) owing to collagen-producing fibroblasts and a dense network of collagen fibers and also to the T2 blackout effect [24, 25, 60]. Fibrothecomas with degeneration may display intermediate to high signal intensity on high-b-value images [33, 64, 65, 71]. The presence of prominent solid components with high T2 signal intensity and strong enhancement are typical for cystadenocarcinofibroma [62].

Fig. 6.3

Cystadenofibroma. A 39-year-old woman with normal CA125. Pelvic MRI demonstrates a left-sided complex, predominantly cystic, adnexal mass. The fluid contents are of high signal intensity on T2-weighted (TR:4361, TE:80; a, b) and T1-weighted images (TR:519, TE:10; c) with no signal loss on the fat-sat images (TR:519, TE:10; d) in keeping with proteinaceous/hemorrhagic materials. There is a papillary “carpet-like” wall thickening on the left anterior aspect of the mass with a very low signal intensity on T1- and T2-weighted images (arrows); this demonstrates mild, delayed contrast medium enhancement (post-gadolinium T1-weighted fat-sat image, d)

6.2.5 Brenner Tumor

Brenner tumors are rare (1–3 %), mostly benign and incidentally found solid tumors, belonging to the epithelial surface derived tumors. They are composed of transitional cells with dense stroma, and a malignant component is rare [54]. They represent about 2–3 % of ovarian tumors and usually occur at a mean age of 50 years. They are usually small (<2 cm), solid, and unilateral [54]. Cystic components can be found in Brenner tumors, and in 20–30 % of cases they are associated with mucinous cystadenomas or other epithelial neoplasm [32, 54, 72, 73]. Brenner tumors may rarely produce estrogen; therefore, they can be associated with endometrial thickening [67]. On T2-weighted MR imaging, the dense fibrous stroma presents low signal intensity, similar to that of a fibroma. Extensive amorphous calcification is often present within the solid component [62, 67, 68]. On DW images, Brenner tumors show both low signal intensity on high-b-value images and low corresponding ADC values (mean 1.156 × 10⁻³ mm²/s) owing to collagen-producing fibroblasts, to a dense network of collagen fibers, and also to the T2 blackout effect [64, 65]. The combination of a multi-septated ovarian tumor with a solid part with extensive calcifications may suggest the presence of a collision tumor consisting of a Brenner tumor and a cystic ovarian neoplasm, like cystadenoma [54].

6.2.6 Dermoid Cyst/Mature Teratoma

These are relatively common benign ovarian lesions, containing structures derived from the three germ cell layers. At imaging, the presence of fat within a cystic ovarian mass is pathognomonic for a mature cystic teratoma [74]. They are the most common ovarian neoplasms below 45 years of age, accounting for up to 70 % of tumors in women below 19 years of age [75]. They are usually unilateral, with only 10–15 % of dermoids found bilaterally [54]. They can be divided into three categories, among which mature cystic teratomas account for 99 %; less common types are the monodermal, which include struma ovarii and carcinoid tumors [54]. Although all three germ cell layers are present, ectodermal components predominate [63]. In the vast majority (88 %), dermoids are unilocular cystic lesions; a protuberance, called Rokitansky nodule or dermoid plug, projects into the cavity and is the hallmark of dermoids. Mature teratomas typically have a lipid content (90 %), consisting of sebaceous fluid, or adipose tissue within the cystic wall or the dermoid plug [73]. The Rokitansky nodule contains a variety of tissues, often including fat and calcifications, which represent teeth (31 %) or abortive bone [54, 74, 76]. A minority (8 %) of dermoid cysts do not demonstrate fat [74]. Dermoids are usually asymptomatic, incidentally discovered, and tend to grow slowly [77, 78]. Malignant degeneration, torsion and rupture, which can cause acute abdomen due to granulomatous peritonitis caused by leakage of the fatty content, can be present [79]; in particular, malignant degeneration, mainly arising from the dermoid plug, occurs in up to 2 % and is usually found in the 6th to 7th decades of life. The risk of malignancy is associated with larger size (>10 cm) and postmenopausal age [80]. Capsule perforation is a sign for malignant transformation of a mature teratoma [81]. At MRI mature teratomas are usually round or oval and sharply delineated; the lipid-laden cyst fluid shows high signal intensity on T1-weighted images and intermediate signal intensity on T2-weighted images (Fig. 6.4). Fat has a high signal intensity on T1- and T2-weighted fast spin-echo images and loss of signal on fat-saturated T1-weighted images. Chemical shift artifacts can be observed, differentiating fat from hemorrhage. There are some typical internal patterns, such as palm tree-like protrusions or dermoid nipples [40, 82, 83]. Calcifications can be missed on MRI due to the low signal intensity on both T1- and T2-weighted images. The presence of sebaceous fluid floating in the peritoneal cavity can suggest rupture [72]. Low ADC values caused by keratin may be useful in differentiation of mature teratomas with little fat from other cystic tumors; despite this, chemical shift imaging seems a better alternative [22, 35, 51]. MR fat-suppressed or chemical shift images are reliable for the differentiation of fat from hemorrhage [84]. In particular, when no or small amounts of fat are present, dermoids cannot be distinguishable from benign cystic ovarian tumors or ovarian cancer [79]. Monodermal teratomas are solid lesions, mainly or exclusively composed of one tissue type. They include struma ovarii, ovarian carcinoid tumors, and tumors with neural differentiation. Monodermal teratomas are typically solid lesions [22]. Struma ovarii is the most common type (3 %); it consists of mature thyroid tissue, but a mixed morphology with acini filled with thyroid colloid, hemorrhage, fibrosis, and necrosis can be found. Rarely, struma ovarii may produce thyrotoxicosis. They present as cystic or multilocular lesions with loculi displaying high signal intensity on T1- and T2-weighted images, without fat [85].

Fig. 6.4

Mature teratoma. A 47-year-old woman with ovarian enlargement on US and normal CA125. Pelvic MRI shows a right-sided complex adnexal mass. There is a fluid–fluid level, as depicted on axial T2-weigted image (TR:4361, TE:80; a) with hyperintense material on the top on axial T1-weighted image (TR:519, TE:10; b), the signal of which is suppressed on fat-saturated T1-weighted pulse sequence (TR:519, TE:10; c) indicative of the presence of fat. There are central areas which are of intermediate signal intensity suggestive of soft tissue (a, arrow) consistent with the typical Rokitansky nodule. These components demonstrate restricted diffusion (hyperintense on the b1000 – d) but do not demonstrate contrast enhancement (c)

6.2.7 Fibroma, Thecoma, and Fibrothecoma

They are sex cord–stromal tumors, composed of spindle cells forming a variable amount of fibrosis and other cells [33] and can occur in both pre- and postmenopausal women. They are solid tumors accounting for 3–4 % of all ovarian tumors, typically unilateral (90 %), occurring in middle-aged and peri- and postmenopausal women. Fibromas are composed of whorled bundles of spindle-shaped fibroblasts with abundant collagen [18, 22, 86]. Fibromas are important from an imaging standpoint because they mimic malignant neoplasms. They can also be associated with ascites and rarely with pleural effusion [87, 88]. The association of an ovarian fibroma, ascites, and pleural effusion is known as Meigs syndrome. Thecomas and fibrothecomas can have estrogenic activity [63]. Bilateral fibromas are also present in basal cell nevus syndrome, along with basal cell carcinomas, bony, ocular, and brain abnormalities as well as other tumors [63].

Fibrothecomas are composed of thecal cells with abundant fibrosis. Unlike fibromas, they can have estrogenic activity and may present with uterine bleeding. In more than 20 %, endometrial carcinomas may be present concomitantly [63]. Because of their abundant collagen content, small fibromas and fibrothecomas have imaging features similar to uterine leiomyomas, with intermediate to low signal intensity on T1-weighted images and hypointensity on T2-weighted images. Larger lesions may have an inhomogenous structure with high signal intensity foci within the low signal intensity lesion, representing edema or cystic degeneration [22, 83, 89] (Fig. 6.5). In larger lesions, dense amorphous calcifications are present but not well appreciated because of their low signal intensity on T2-weighted images. Fibromas and fibrothecomas tend to show mild or delayed gadolinium enhancement [22, 83]. Differential diagnosis should be made with ovarian lesions with fibrous components other than fibroma and fibrothecomas that are cystadenofibroma and Brenner tumor [35, 82]. Pedunculated uterine leiomyomas and broad-ligament leiomyomas can appear as ovarian masses and have the same signal intensity features of fibromas and fibrothecomas. The recognition of the interface vessels between the uterus and adnexal mass is a useful tool in differentiating leiomyomas from ovarian fibromas [90, 91].

Fig. 6.5

Ovarian fibroma. A 55-year-old lady with pain on the left pelvis. Left ovarian mass showing very low signal intensity on T2-weighted images (axial and sagittal T2-weighted images, TR:4361, TE:80; a, b) and low signal intensity on T1-weighted image (coronal T1-weighted imaging without and with fat saturation, TR:519, TE:10; c, d) in keeping with a fibroma. There is a further small cyst at the posterior margin of the fibroma (arrow). The right ovary shows a small follicular cyst (curved arrow)

6.2.8 Sclerosing Stromal Tumor

Sclerosing stromal tumors are rare benign ovarian tumors occurring in young women [92]. They present as large masses with cystic and solid components. On MRI, they show a mixed hyper- and hypointense appearance on T2-weighted images. On dynamic images, the tumors show early peripheral enhancement with centripetal progression. A central area of prolonged enhancement of the mass represents fibrous hypocellular areas. The appearance after contrast medium administration is useful to differentiate sclerosing stromal tumors from fibromas [85, 93, 94].

6.3 Malignant Neoplasms

6.3.1 Epidemiology and Clinical Features

Worldwide, ovarian cancer accounts for 4 % of all female cancers and is the most frequent cause of death from gynecological malignancy with 239 new cases/year. In the majority of cases, it is a sporadic tumor and presents over the age of 30 years. There is a correlation between age distribution and tumor histology. Epithelial ovarian carcinomas usually present in postmenopausal women, whereas sex cord–stromal tumors and germ cell tumors are prevalent in young women around the age of 20–30 years. Several risk factors for ovarian cancer have been identified: increasing age, nulliparity, early menarche, late menopause, and long-term hormone replacement therapy. There are three recognized hereditary forms of ovarian cancer: breast–ovarian familial cancer syndrome (related to BRCA1 gene mutation), multiple site cancer family syndrome (Lynch II syndrome) and site-specific ovarian cancer. These tumors account for 5–10 % of the total cases; they tend to present mostly in premenopausal women and cause an increased –around 50 % – lifetime risk of developing ovarian carcinoma [95].

The most frequent clinical presentation of all ovarian malignancies consists of abdominal pain and swelling due to the fact that the tumor tends to manifest itself only when it has reached a large size. Functional ovarian neoplasms may present with specific endocrine and non-endocrine syndromes [96]. CA125 is currently the most commonly used serum marker for ovarian cancer, particularly in monitoring treated patients. Its role for initial diagnosis and staging is limited due to low sensitivity and specificity, particularly for stage I ovarian carcinoma. It also has a high false-positive rate in premenopausal women [97].

6.3.2 Staging

The gold standard for staging ovarian cancer remains surgery according to the International Federation of Gynaecology and Obstetrics (FIGO) guidelines. Those are based on the concept that ovarian cancer spreads centrifugally from the pelvis into the peritoneal cavity metastasizing outside the peritoneum only in advanced disease (National Comprehensive Cancer Network - NCCN guidelines for ovarian cancer). A TNM classification has also been defined [98] (Table 6.2).

Table 6.2 TNM staging of ovarian cancer

Cross-sectional imaging staging is warranted for complex adnexal mass highly suggestive of malignancy (after US and/or CE-MRI) or for a noninflammatory complex adnexal mass with associated ascites. The main targets of preoperative staging are:

• Confirmation of malignant adnexal mass

• Tumor burden assessment with metastatic site determination and possible complication assessment (bowel obstruction, hydronephrosis, or venous thrombosis)

• Exclusion of a different primary site (GI tract, pancreas)

Multidetector computer tomography (MDCT) is the imaging technique of choice in ovarian cancer staging and follow-up. MRI is a second-line technique for staging mainly due to the long examination time and limitations covering large field of view. Despite this MRI becomes first line for preoperative staging in specific situations:

• Contraindication to contrast medium administration (allergy)

• Pregnancy

• Young age

When MRI is used to assess disease burden, DWI with high b-values should always be included to assess peritoneal deposits due to its high sensitivity [99].

PET/CT may also be used for staging as an alternative to CT or MRI, particularly in patients presenting with pleural effusion and/or suprarenal lymphadenopathy [100]. Nevertheless PET/CT should be used carefully in early-stage disease due to its high rate of false-positive results [101].

Finally, it should be kept in mind that the optimal coverage for staging ovarian cancer by CT or MRI includes imaging from lung bases to the inguinal region [102].

6.3.3 Pathology and MRI Correlation

Ovarian neoplasms were classified by the World Health Organization (WHO) according to the tissue of origin into surface epithelial tumors, germ cell tumors, and sex cord–stromal tumors. These are further divided into benign, borderline, or malignant, which reflects their clinical behavior and prognosis [103].

6.3.4 Surface Epithelial Tumors

6.3.4.1 Borderline Epithelial Tumors

Borderline tumors (BOTs) are a unique entity of ovarian neoplasms without infiltrative destructive growth or stromal invasion. They represent 15–20 % of all ovarian tumors and usually affect younger women when compared to invasive carcinoma. They occur in all types of epithelial ovarian tumors, but are more common in serous and mucinous subtypes. They are associated with normal or minimally elevated CA125 level and are usually diagnosed at early stage. Up to 30 % of cases are bilateral. Use of fertility drugs and contraceptives has been correlated to an increased incidence of these tumors in the past decades. Endometriosis is also a recognized precursor for endometrioid and clear cell borderline tumors. Peritoneal implants may be present at the diagnosis, particularly in the serous subtype. Nevertheless, prognosis is better than that of common invasive epithelial ovarian cancer.

As these tumors affect young women who should be offered fertility-sparing surgery, identification of BOTs is a critical challenge for imaging. Despite several authors’ efforts in identifying morphological imaging features suggestive of borderline lesions [104, 105], no specific findings have been demonstrated so far. In fact there is still a significant overlap with imaging features of invasive malignancy.

As reported in the literature, disease assessment should include confirmation of ipsilateral normal-appearing ovarian stroma and examination of the contralateral ovary to allow clinical decision towards fertility-preserving surgery. Furthermore, since the presence of invasive peritoneal implants significantly affects prognosis, assessment of peritoneal/omental disease and lymphadenopathy using MRI with DWI and complete surgical staging are mandatory.

6.3.4.1.1 Serous Borderline Neoplasm of the Ovary

Serous borderline tumors are the most common accounting for approximately 65 % of all BOTs [106]. Mean age at presentation is 34–40 years. These are slowly growing lesions that may exhibit an aggressive behavior consistent with peritoneal implants and regional lymphadenopathy (35 and 27 %, respectively). These peritoneal implants are classified as noninvasive (serous papillae in cystic spaces or plastered on the peritoneal surface, without invasion of the underlying tissue) or invasive (with invasion by haphazardly distributed glands and small cell clusters accompanied by a dense stromal reaction) – the latter having a poorer prognosis.

On MRI borderline serous ovarian tumors manifest as complex predominantly cystic mass (bilateral in 30 % of cases) with thin septa and endocystic or exocystic vegetations showing moderate early enhancement on dynamic MR imaging [107]. DW-MRI should be included to improve peritoneal implant detection, even if at the diagnosis 70 % of serous BOT are confined to the ovary (Fig. 6.6).

Fig. 6.6

Borderline serous cystadenoma low grade. A 30-year-old woman with bilateral complex cystic adnexal masses (sagittal and axial T2 images, TR:4361, TE:80; a–c); the largest on the right shows multiple papillary projections (arrows). No restricted diffusion is demonstrated (b0, b750, and ADC map, d–f)

6.3.4.1.2 Mucinous Borderline Neoplasm of the Ovary

Mucinous borderline tumors of the ovary comprise 32 % of all BOTs. Mean age at presentation is 45 years. There are two distinct subtypes: the intestinal (90 %) and the mullerian (10 %) histotypes. The first one is usually unilateral and associated with pseudomyxoma peritonei in up to 17 % of cases. The second one is bilateral in 40 % of cases and associated with endometriosis in one-third of cases. On MRI they manifest as multilocular cystic mass with numerous septa containing fluids of variable signal intensities on T1- and T2-weighted images (stained glass appearance). The endocystic vegetations usually show delayed uptake of contrast medium [108] on DCE-MRI. The mullerian subtype tends to present as uni- or paucilocular cyst with mural enhancing nodules. At diagnosis up to 82 % of mucinous BOTs are confined to the ovary with peritoneal implants less common compared to serous BOTs.

6.3.4.2 Invasive Epithelial Tumors

Surface epithelial carcinomas represent 85–90 % of all ovarian malignancies. These consist in serous, mucinous, endometrioid, and clear cell carcinoma.

6.3.4.2.1 Serous Adenocarcinoma

Malignant serous tumors represent one-third of all ovarian serous neoplasms and approximately 50 % of all ovarian malignancies, with serous cystadenocarcinoma being the most common type of surface epithelial ovarian cancer [109]. More than 60 % of serous cystadenocarcinomas are bilateral. On MRI they usually manifest as predominantly cystic, unilocular or multilocular masses with multiple thick septations, mural nodules, and papillary projections avidly enhancing after contrast medium administration. Areas of hemorrhage (bright on T1- and variable on T2-weighted images with no signal drop on fat-sat images) or necrosis are common. Calcifications may be present – psammoma bodies with microscopic calcifications in 30 % of cases [110] (Fig. 6.7). Peritoneal implants are frequent in advanced stage disease. Bowel obstruction and hydronephrosis should always be considered as possible complications.

Fig. 6.7

High grade ovarian serous cystadenocarcinoma. A 33-year-old woman with a rapidly enlarging pelvic mass and elevated CA125. Pelvic MRI demonstrates bilateral adnexal masses with solid components of intermediate signal intensity on T2-weighted images (TR:4361, TE:80; a, b) and predominantly low signal intensity on T1-weighted image (TR:519, TE:10; c). The solid components are avidly enhancing post-contrast medium injection (d) and demonstrate marked hyperintensity on b1000 DWI (e) with restricted signal on the corresponding ADC map (f). There is ascites with peritoneal disease (arrows). Note the high sensitivity of the high-b-value DWI for peritoneal implant detection

6.3.4.2.2 Mucinous Adenocarcinoma

Malignant mucinous tumors represent 5–10 % of all malignant ovarian tumors and are the second more common type of epithelial ovarian cancer. They tend to be larger than serous ones, but less frequently bilateral (only 20 %) [87]. On MRI they present as multilocular complex cystic masses, with honeycomb-like locules. Because of the variable protein and mucinous contents, these loculi show variable high signal on T1- and T2-weighted images configuring the so-called stained glass appearance (Fig. 6.8). Compared to borderline, invasive mucinous carcinomas have thick septa and avidly enhancing solid components. Pseudomyxoma peritonei may be associated with the intestinal subtype with large amount of fluid-like (mucoid) material throughout the abdomen surrounding mesentery, bowel, and solid organs [29].

Fig. 6.8

Mucinous adenocarcinoma. A 25-year-old lady with abdominal pain and elevated CA125. There is a large multiloculated, predominantly cystic pelvic mass. The locules contain variable hyperintense fluid on T2-weighted images (TR:4361, TE:80; images a–c), while others contain mildly hyperintense components on T1-weighted image, suggestive of hemorrhage/mucin (TR:519, TE:10; d). No areas of fat saturation (e). There are numerous thick septa and enhancing solid components (f, arrows)

6.3.4.2.3 Endometrioid Adenocarcinoma

Endometrioid adenocarcinoma of the ovary is a primary ovarian surface epithelial carcinoma histologically identical to a typical adenocarcinoma arising from the endometrium. It represents 5.7 % of ovarian surface epithelial neoplasms, 17.5 % of all ovarian carcinomas, and the third most common type of ovarian malignancy after serous and mucinous cystadenocarcinomas. It can be bilateral in up to 30 % of cases. There is a well-established correlation between endometrioid adenocarcinoma, endometriosis, and endometrioid hyperplasia. Simultaneous manifestation of endometriomas and ovarian endometrioid adenocarcinoma occurs in 15–25 % of cases [111]. Kitajima et al compared contrast-enhanced MRI appearance of ovarian endometrioid adenocarcinoma arising or not arising from endometrioma, and they found interesting differences. Tumors arising from endometriomas usually present on T1-weighted imaging as low to intermediate nodules within a predominantly cystic mass. They also have a lower nuclear grade and are diagnosed at a less advanced clinical stage (Fig. 6.9). On the other hand, tumors not arising from endometriomas present as solid masses with a higher nuclear grade and more advanced clinical stage. Furthermore, endometrioid adenocarcinoma arising from endometriomas does not show the characteristic “shading effect” of benign endometriomas consistent in T1 hyperintensity with layering T2 hyper-/hypointensity due to the magnetic susceptibility effect of old hemorrhage or densely concentrated fluid/fibrosis [40, 112].

Fig. 6.9

Grade 1 endometrioid carcinoma in a background of diffuse endometriosis. A 52-year-old lady with a large right-sided predominantly solid pelvic mass. This demonstrates low signal intensity on T1-weighted image (TR:519, TE:10; a) and heterogeneous signal intensity on T2-weighted images (TR:4361, TE:80; b–d). Note large feeding vessels, best seen on sagittal image (c, arrow). There is a fibrotic plaque tethering the sigmoid bowel as a result of previous endometriosis (curved arrow)

6.3.4.2.4 Clear Cell Carcinoma

Clear cell carcinoma (CCC) represents approximately 5 % of all ovarian carcinomas and usually affects women in peri–postmenopausal age (around the age of 50 years). Up to 20 % of cases are bilateral. Despite the fact that this tumor is almost always malignant, the overall prognosis is good, as it tends to remain confined to the ovary with up to 75 % of patients presenting with stage I disease [113]. The survival rate is of 50 % at 5 years from the diagnosis. Recurrent CCC is more aggressive with distant organs and lymph node involvement occurring in 40 % of cases. There is a correlation with nulliparity and endometriosis; when arising within benign endometriomas, CCC tends to have a worse prognosis. On MRI CCCs usually appear as unilocular cystic masses with smooth margins, larger than 4 cm with cystic contents from low to very high T1 signal intensity and always high T2 signal. They can be either predominantly solid or cystic with one or more solid protrusions [114].

6.3.4.2.5 Brenner Tumor

Brenner tumors are uncommon transitional cell tumors of the ovary, accounting for about 2 % of ovarian neoplasms. The majority of them are benign, but borderline and malignant types can also arise. When malignant they tend to present later (around the age of 60 years) compared to the benign form (mean age at presentation of 40–60 years). They are usually discovered as incidental findings during surgery, transvaginal ultrasound, or MRI (over 90 % of them) [115]. While benign Brenner tumors are cured by local excision, the malignant ones are incurable with a very poor prognosis. Borderline Brenner tumors have intermediate histological appearance and aggressiveness compared to the benign and malignant types. Malignant tumors are usually larger than the benign ones, with an average of 8–10 cm in diameter. They may present with nonspecific symptoms including abdominal distention, pain, and PV bleeding. On MRI, malignant Brenner tumors may appear as multiloculated cystic masses with heterogeneously enhancing solid components and papillary projections. The cystic components are of high signal intensity on T2-weighted imaging. Interestingly, the benign form tends to appear as predominantly solid mass of low signal intensity on both T1- and T2-weighted imaging with calcifications and rapid enhancement after contrast medium administration [72, 116, 117]. Differential diagnosis should include solid ovarian masses with or without calcification on CT and MRI, such as benign teratoma, fibroma–thecoma, granulosa cell tumor, Krukenberg tumor, and primary lymphoma. About 30 % of Brenner tumors occur in association with ipsilateral ovarian tumors such as mucinous cystadenomas [118].

6.3.5 Sex Cord–Stromal Tumors

Sex cord tumors account for 5–10 % of all ovarian malignancies and derive from sex cord and specialized stroma of the developing gonads [119]. They can differentiate into an ovarian direction (granulosa–theca cells), into a testicular direction (Sertoli–Leydig), or into a stromal–fibromatous direction. They may occur from childhood (5 % of all malignancies in this age) to reproductive age and postmenopausal phase, being more common after menarche. These tumors are also the most common functional neoplasms of the ovary [3].

6.3.5.1 Granulosa Cell Tumor

Granulosa cell tumors (GCT) derive from the cells surrounding the developing follicles. There are two different histological types: adult and juvenile. The adult type is of low malignant potential and occurs usually in peri- and postmenopausal age, with a peak of prevalence in 50–55-year-old women. It accounts for 95 % of all GCT and represents 5–10 % of solid ovarian tumors. The adult type is far more common than the juvenile type [120, 121]. Because these tumors produce estrogen, they are associated with endometrial hyperplasia, polyps, or carcinoma (usually well differentiated, occurring in 3–25 % of patients) and can manifest with irregular bleeding in premenopausal patients or postmenopausal bleeding [122]. There is a rare form that can produce androgen and is usually associated with purely cystic tumors [16]. Juvenile GCT constitutes only 5 % of all GCTs with a mean age of 13 years. Only 3 % of these tumors occur in women older than 30 years. In the most frequent case, it occurs in premenarchal girls causing sexual precocity because of the estrogen production [123]. Adult and juvenile GCTs have similar appearance on imaging. They are commonly unilateral solid or mostly solid masses and rarely cystic. Because of hemorrhage within the tumor, they usually show hyperintensity on T1-weighted images. When cystic they tend to be multilocular with a typical “spongelike” appearance on T2-weighted imaging [124, 125]. Solid components demonstrate enhancement on post-gadolinium images. The histological features are not related to an accurate prediction of clinical behavior. Around 90 % of adult GCTs are found at stage I with a consequent excellent prognosis. Metastases and recurrences commonly occur long after surgery with a slow growth rate [126].

6.3.5.2 Sertoli–Stromal Tumor

Sertoli–stromal tumors are classified into Sertoli, stromal–Leydig, and Sertoli–Leydig cell tumors. Sertoli cell tumors account for only 4 % of these tumors and are usually non-functioning. Stromal–Leydig cell tumors are extremely rare (0.5 % of all ovarian tumors). They usually occur in women around the age of 30 years or younger. Less than 10 % of affected patients are over the age of 50 years. About 30 % of patients show virilization, manifested by amenorrhea or virilized secondary sexual characteristics, while 50 % have no hormonal manifestations [127]. Only occasionally these tumors can produce estrogens. They are rarely bilateral and have a variable appearance being either solid, mixed solid–cystic, or purely cystic. They may appear as a well-defined enhancing solid mass with or without multiple variable-sized cystic areas [23]. When they cause virilization, they are commonly small and difficult to detect on MRI [128]. Usually these small steroid-secreting tumors show high signal intensity on T1-weighted images because of the lipid content and avid enhancement after contrast administration. Low signal intensity on T2-weighted imaging depends on the extent of fibrous stroma (Fig. 6.10). They are microscopically ranged from well differentiated to poorly differentiated with accordance to clinical behavior. Most of them are stage I at diagnoses and behave in a benign way [20]. Recurrence tends to occur soon after initial diagnosis.

Fig. 6.10

Poorly differentiated Sertoli–Leydig ovarian tumor. Left-sided solid ovarian mass (arrow) in a 23-year-old patient with oligomenorrhea and excessive hair growth. The mass demonstrates intermediate signal intensity on T1- and T2-weighted images (TR:519, TE:10 and TR:4361, TE:80; a–c) and avid contrast medium enhancement (d). There is hyperintensity on the b1000 DWI (e) with hypointensity on the corresponding ADC map (f) indicating restricted diffusion

6.3.5.3 Steroid Cell Tumor

Steroid cell tumors account for 0.1–0.2 % of all ovarian tumors and include three subtypes: stromal luteoma, Leydig (or hilus) cell tumor, and steroid cell tumor not otherwise specified [16]. They are all formed by typical steroid-secreting cells, including lutein cells, Leydig cells, and adrenocortical cells with abundant intracellular lipid. For these reasons these tumors are also called lipid or lipoid cell tumors. Mean age at presentation is around 50–60 years, but they can affect women of all ages. At imaging they usually appear as unilateral solid tumors, sometimes with small areas of cystic change or necrosis. When they cause virilization they are commonly small. Because of the presence of a high content of lipids, they show high signal intensity on T1-weighted imaging. Some authors suggested that chemical shift imaging can help in identifying the presence of intratumoral lipids [129]. After contrast administration they show intense enhancement because of the abundant blood vessels supplying the tumorous tissue. When they don’t cause virilization, they are larger with a lobulated, solid appearance [8].

6.3.6 Germ Cell Tumors

6.3.6.1 Immature Teratoma

Immature teratoma represents less than 1 % of all teratomas and contains immature tissue from all three germ cell layers. It typically presents in the first two decades of life. In 26 % of cases it is associated with an ipsilateral mature teratoma and in 10 % of cases with an immature teratoma in the contralateral ovary [130]. Immature teratomas tend to present as large, complex masses with cystic and solid components and scattered calcifications, while mature teratomas tend to be smaller with calcifications usually associated to mural nodules [81]. The fat distribution is typical in immature teratomas with small, punctuated foci of fatty tissue scattered throughout the tumor; homogeneous larger fat deposits are present in benign lesions. Gradient echo sequences can be helpful in identifying small fat components in immature teratomas. Tumor capsule is not always well defined and can be perforated by rapid tumor growth. On MR solid tissue shows a wide variety of signal intensities on T2-weighted images (Fig. 6.11). Ascites and peritoneal dissemination can be observed [5, 131]. Despite several studies attempting to define specific features on conventional and functional MRI (DCE-MRI; DW-MRI) for the identification of immature teratomas, the differential diagnosis between the immature and the mature form remains challenging [71, 132].

Fig. 6.11

Immature teratoma grade 2. A 27-year-old woman with a large, mixed cystic and solid, pelvic mass. The mass demonstrates heterogeneous T2/T1 signal intensity (TR:4361, TE:80 and TR:519, TE:10; a–c) and avid contrast medium enhancement (d). The solid components are hyperintense on b1000 image (e) and hypointense on the corresponding ADC map (f) indicating restricted diffusion. A few small areas of fat are present throughout the mass and best demonstrated on the T1-weighted, fat-saturated pulse sequence image (TR:519, TE:10; d, arrow)

6.3.6.2 Dysgerminoma

Dysgerminomas are rare ovarian tumors (3–5 % of all ovarian malignancies) that affect usually young women (less than 30 years old). They are usually not associated with endocrine hormone secretion. An elevated HCG serum level can be found in 5 % of cases: this is due to the presence of syncytiotrophoblastic giant cells able to produce HCG [26]. On MRI, they appear as multiloculated solid masses with prominent fibrovascular septa hypointense or isointense on T2-weighted imaging, with avid enhancement after contrast administration on T1-weighted imaging. As recently demonstrated, these septa correspond to fibrovascular bundles at histologic examination [133]. Calcifications may be present in a speckled pattern together with necrosis and hemorrhage [27, 30], the latter appearing as high signal intensity on T1-weighted imaging.

6.3.6.3 Choriocarcinoma

Primary ovarian choriocarcinoma is an extremely rare germ cell tumor that occurs almost exclusively in patients younger than 20 years [134]. This is an aggressive tumor that usually has already metastasized to the lungs, liver, and bones by the time of presentation. In patients of reproductive age, a metastatic origin from uterine malignancy or a tumor arising from an ectopic ovarian pregnancy should be considered. Other forms of malignant germ cell neoplasms such as immature teratoma may present in association with this tumor. On MRI, it is usually unilateral and predominantly solid with hemorrhage and necrosis [31]. The main biochemical feature is the concomitant elevated serum HCG level [26].

6.3.6.4 Carcinoid Tumor

Ovarian carcinoids are extremely rare neoplasms, accounting for 0.3 % of all carcinoid tumors and for 0.1 % of all malignant ovarian tumors [135]. They usually have a low grade malignant potential, being benign in 95 % of cases. They are classically diagnosed as unilateral enhancing solid nodules often within the wall of mature cystic teratomas. When presenting as isolated enhancing masses, it is not possible to discriminate from a solid malignancy. They can also be associated to mucinous neoplasms. In the majority of cases they are asymptomatic, but in some cases typical carcinoid syndrome or constipation due to secretion of peptide YY can occur. On MRI they typically show low signal on T2-weighted images as almost all benign fibrous neoplasms. These tumors also tend to exhibit high signal intensity on diffusion-weighted imaging with low ADC values and hypervascularity on dynamic studies after contrast medium administration [136].

6.3.7 Other Rare Tumors

6.3.7.1 Mixed Mullerian Tumor

Mixed Mullerian tumors represent less than 1 % of all ovarian neoplasms and contain both epithelial and sarcomatous elements [137, 138]. They can originate anywhere along the female genital tract and in the peritoneum; the most frequent location is the uterus, but they can be found in the ovary, vagina, cervix, and fallopian tubes [139]. They are always malignant with very poor prognosis and usually diagnosed at advanced stage (70 % at stage III and IV) in postmenopausal women. On MRI they appear as large (even more than 10 cm), well-encapsulated, multinodular, and multicystic masses with very heterogeneous appearance and enhancing solid elements (papillary projections). Fluid–fluid levels within multilocular cystic components may be present due to old hemorrhage. The enhancement patterns can be extremely variable as well [140]. Secondary signs of malignancy such as ascites and metastases are usual findings at presentation.

6.3.7.2 Lymphoma

Ovarian involvement by a malignant lymphoma is usually a manifestation of disseminated disease. Primary lymphoma of the ovary is very rare, likewise other primary lymphomas of the genital tract, and accounts for 0.5 % of all non-Hodgkin’s lymphomas and 1.5 % of all malignant ovarian neoplasms. Since there is no lymphoid tissue within the ovary, the tumor may originate from lymphocytes surrounding blood vessels or related to the corpus luteum. Diagnosis of primary ovarian lymphoma should be suggested when the tumor is confined to the ovary and regional lymph nodes or adjacent organs with no abnormal cells found in bone marrow and peripheral blood [141–144]. Non-Hodgkin’s large B cell lymphoma is the most common type of lymphoma involving the ovary. It manifests as a large solid mass with a very rapid growth that must be differentiated from other predominantly solid tumors such as thecoma, fibroma, Brenner tumor, immature germ cell tumor, or granulocytic sarcoma. They present as unilateral or bilateral homogeneous adnexal masses without ascites. On MRI, the solid masses appear of intermediate signal intensity on T1- and T2-weighted imaging, with homogeneous enhancement after contrast administration. Several small cysts in a linear arrangement at the periphery of the mass may be present consisting of preserved follicles at the periphery of the ovary [145, 146]. Prognosis is the same as that of a NHL arising in a different site of the body.

6.3.7.3 Sarcoma

Sarcomas of the ovary are very rare neoplasms. In the literature fibrosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, angiosarcoma, rhabdomyosarcoma, osteosarcoma, and chondrosarcoma have been described as sporadic cases [147–153]. At MRI they show as a large tumor mass with heterogeneous high intensity on T2-weighted images and low intensity on T1-weighted images, with laminar or stripe-like enhancement. Hemorrhage and necrosis can be displayed in these lesions [154].

6.3.8 Metastases

Metastatic tumors of the ovary represent about 5–10 % of ovarian neoplasms. The ovary is a relatively preferential site of metastatic disease, as neoplastic cells can easily reach the ovary through hematogenous, lymphatic, and transperitoneal spread and/or direct extension. About 7 % of lesions clinically presenting as primary ovarian tumors are metastatic in origin. The most common primary tumors that metastasize to the ovary are stomach (Krukenberg tumor), colon, breast, and endometrial malignancies. Less frequently tumors arising from the pancreas, biliary duct, and lung may spread to the adnexal [155, 156]. A detailed clinical history is mandatory as ovarian secondarism may occasionally be the only initial manifestation of the disease, particularly in cancers of the gastrointestinal tract [157].

6.3.8.1 Krukenberg Tumor

Krukenberg tumor refers to bilateral ovarian metastases characterized by mucin-producing signet ring cells, most commonly from gastric cancer. Metastatic cells from gastric cancer easily penetrate the ovary and tend to stimulate a dense stromal reaction with variable degree of luteinization mimicking a fibroma or another spindle cell tumor. Morphologically most of these tumors are lobulated and complex consisting of solid elements with cystic areas. On MRI the solid components typically show heterogeneous signal intensity at T2-weighted imaging, related to the degree of stromal overgrowth and the amount of mucin produced (Fig. 6.12). Low signal intensity areas correspond to increased cellularity of fibrous stroma, whereas high signal intensities correspond to edema within the connective tissue and mucin [158]. Intratumoral cysts can be occasionally associated. Signal voids can be observed within the tumors, those representing increased tumor vascularity. After contrast administration the solid component shows homogeneous enhancement [158].

Fig. 6.12

Krukenberg. A 56-year-old patient with gastric adenocarcinoma and elevated CA125. There is a large pelvic mass with heterogeneous high signal intensity on T2-weighted images (TR:4361, TE:80; a, b) and low signal intensity on T1-weighted image (TR:519, TE:10; c). The mass is predominantly solid with avid peripheral enhancement after i.v. contrast medium administration (d)

6.3.9 Collision Tumors

Collision tumors represent the coexistence of two histologically distinct but not mixed tumors. These tumors have been reported in various organs such as the brain, esophagus, stomach, liver, lung, thyroid, bone, uterus, ovary, kidney, adrenal gland, skin, paranasal sinus, and lymph nodes. Ovarian collision tumors are rare entities, most commonly composed of teratomas in combination with benign, borderline, or invasive epithelial tumors. Prognosis and treatment depend on tumor types present. Preoperative suggestion of a collision tumor is crucial, leading the pathologist to perform a thorough examination of the mass to diagnose the composing tumor types. A correct definition of these is critical for further patient management and prognosis [159]. When an ovarian tumor demonstrates imaging findings that cannot be subsumed as one specific histological type, especially in cases of ovarian teratoma, a collision tumor should be considered [159].