Contents

I. Thomassin-Naggara (*)

Sorbonne Universités, UPMC Univ Paris 06, IUC, 75005 Paris, France

INSERM, UMR970, Equipe 2, Imagerie de l’angiogenèse, 75005 Paris, France

Department of Radiology, AP-HP, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, France

Service de Radiologie, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, France e-mail: isabelle.thomassin@aphp.fr

B. Fedida

Sorbonne Universités, UPMC Univ Paris 06, IUC, 75005 Paris, France

Department of Radiology, AP-HP, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, France

E. Kermarrec

Department of Radiology, AP-HP, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, France

Abstract

Pelvic MR imaging is the best second-line technique­ to characterize indeterminate or complex adnexal masses detected at transvaginal ultrasonography. The aim of this text is to explain the added value of MR and CT in the diagnostic management of a slightly symptomatic indeterminate or complex adnexal mass. The objectives of this chapter are to describe the place of MR imaging and CT imaging and to learn how to combine features from morphologic and functional sequences to accurately diagnose an adnexal mass.

The analysis is divided into two steps: The first step is to estimate the risk of malignancy based on the ADNEX MR Scoring system or EURAD score and the second step is to suggest an histopathological hypothesis combining EURAD score with the age of the patient and the morphology of the tumor.

1\ Introduction

Pelvic MR imaging is the best second-line technique to characterize indeterminate or complex adnexal masses detected at transvaginal ultrasonography.

In clinical routine, there are two very different circumstances for detecting these masses at ultrasonography. The first situation is the context of acute or subacute pelvic pain and the second one is incidental finding of an adnexal mass during

the assessment of a nonspecific symptom such as bleeding, chronic pelvic pain, or infertility.

In this chapter, we are not going to develop the first clinical situation which will be covered in the “Acute and chronic pelvic pain disorders” chapter about pelvic inflammatory disease and adnexal torsion. The aim of this text is to explain the added value of MR and CT in the diagnostic management of a slightly symptomatic indeterminate or complex adnexal mass.

The objectives of this chapter are to describe the place of MR imaging and CT imaging and to learn how to combine features from morphologic and functional sequences to accurately diagnose an adnexal mass.

2\ Part 1: MR Imaging

in Diagnostic Pathway

2.1\ Context

Most of the medical imaging publications recommend MR imaging to characterize complex adnexal masses without any consensus on the definition of the word “complex”. Despite a high level of evidence on the performance of MR imaging in this issue, many clinicians perform laparoscopy just based on ultrasonographic features. However, recent data on the impact of ovarian surgery on fertility are modifying the practices and render MR imaging useful especially to obtain criteria to avoid unnecessary surgery in patients with benign lesions (Buys et al. 2005). Another significant impact of MRI is the possibility to plan the surgical procedure time and then to improve the organization of our overloaded theater schedule. The surgeon needs to correctly plan the surgery and also to inform the patient of the possibility and the risks to discover unexpected lesions during the surgery. That’s why we perform more and more MR imaging in this indication.

2.2\ Which Lesions Should

Be Assessed with MR

Imaging?

MR imaging is a second-line technique after ultrasonography which is the first imaging technique to

assess pelvis abnormalities. More than 70% of adnexal masses are accurately identified using transvaginal ultrasonography with color Doppler. According to the literature, even using accurate ultrasonographic models, 20–25% of adnexal masses remain indeterminate after ultrasonography and need further examination (Kinkel et al. 2005).

To approach the definition of a complex adnexal mass, pattern recognition analysis or simple rules, which are currently the most reliable model published until now, can be used (Brun et al. 2014).

2.2.1\ Indications According

to Ultrasonographic Patterns

The main ultrasonographic patterns are divided into the following six categories:

US pattern 1: Simple cyst (i.e., unilocular anechoic cyst without solid component)

US pattern 2: Nonsimple cyst (i.e., unilocular echoic cyst without solid component)

These two first US patterns are included in the first categories of International Ovarian Tumor Analysis group classification named “Unilocular cyst” (Buys et al. 2005). This group includes the tubal benign abnormalities like hydrosalpinx, hematosalpinx, and the different echoic signal like “ground glass,” “hemorrhagic content,” and “mixed content.”

US pattern 3: Bior multilocular cyst (i.e., bior multilocular cyst without solid component)

US pattern 4: Cyst with papillary projections US pattern 5: Mixed heterogeneous mass IOTA classification groups these two last pat-

terns in the groups “unilocular solid” or “multilocular solid”. In these two categories, there is a cystic and a solid component in the described lesion.

US pattern 6: Enlarged ovaries (including purely solid mass than means more than 80% of solid component in the lesion)

These last three patterns require an ultrasonographic characterization of their solid component looking for acoustic shadowing, irregularity of the margins, and feature of the Doppler flow. These elements are usually inadequate to accurately predict the risk of malignancy.

Therefore, MR imaging can be performed in the cases with US pattern 4, 5, or 6 to suggest a histopathological diagnosis. In pattern 3, MR

imaging allows to exclude a solid component and to characterize the different cystic components and it also helps to approach a histological diagnosis.

On the contrary, in categories 1 and 2, MR imaging has a very low added value except if the lesion is very large. Indeed, if an echoic cyst is larger than 7 cm or an anechoic cyst is larger than 10 cm, MRI is better to exclude a small solid component distant from the endovaginal probe that could be missed. MRI is also efficient to evaluate any associated findings such as deep pelvic endometriosis associated with endometrioma.

2.2.2\ Indications According to Simple Rules

The simple rules described by IOTA group consist in dividing ten sonographic features in two groups: benign features (B features) and malignant features (M features) (Table 1).

When at least one B feature is found and no M feature, the lesion is considered as benign whereas when at least one M feature is found and no B feature, the lesion is considered as malignant. When both B and M features are found, the lesion is considered as indeterminate as well as

Table 1  Simples rules (Timmerman et al. 2010)

when none B or M features is found. Applying these rules, in the group of indeterminate lesion, the risk of malignancy is 40% and MR imaging is warranted (Timmerman et al. 2010).

Recently, Timmerman et al. reviewed the level of risk according to the simple rules’ categories publishing a model of prediction of malignancy on a population of 4848 patients with a prevalence of malignancy of 34.3% (1665/4848) (Timmerman et al. 2010). This new publication suggests that the lesions categorized with an “intermediate risk” (i.e., risk of 8.3%) may also be referred for MR imaging to obtain additional findings to predict benignity (Table 2).

2.3\ Why MR Imaging Is Useful

to Characterize Adnexal

Masses?

Adnexal masses usually have multiple cystic and solid components. If the cyst is anechoic, ultrasonography is accurate to diagnose simple fluid (water-like appearance). If the mass is echoic, the presence of positive Doppler Flow allows ­identifying solid components. But the presence of solid component does not correspond to malignancy whereas the absence of positive Doppler Flow does not help to distinguish hypovascular solid components from nonsimple fluid lesions. The motion of the echos and the presence of a fluid level are in keeping with a nonsimple cyst. However in this type of mass, a solid tissue can be difficult to exclude.

Using pelvic MR imaging, the absence of contrast enhancement in an adnexal mass allows to exclude the presence of solid tissue if the spatial resolution is thin enough (< or =3 mm). Moreover,

Table 2  Risk of malignancy­ of US lesions according the simples rules (Timmerman et al. 2010)

the combination of T2W, T1W, DW, and T1W after intravenous injection of chelates of gadolinium allows recognizing most cystic components seen in adnexal masses. The addition of DW and DCE MR imaging is reliable to characterize solid components distinguishing between benign, borderline, and invasive malignant tissue. By definition, a solid tissue enhances after gadolinium injection. However, any internal enhancement does not correspond to solid tissue. A solid tissue includes solid papillary projection, irregular septa, mural nodule, and purely solid mass (Thomassin-Naggara et al. 2013). Smooth septa whatever the thickness is considered as solid component but not solid tissue.

Thus, MR imaging analysis is performed in two steps: the first step evaluates the risk of malignancy and the second step addresses the histopathological type of ovarian or tubal tumors.

3\ Part 2: MR Protocol and Keys

for Analysis

3.1\ Step 1: Prediction of the Risk

of Malignancy

When a pelvis mass is discovered, the first step is to determine its origin. Thus, normal ipsilateral ovarian parenchyma needs to be identified either as a crescent at the periphery of the mass or in a different site distant from the pelvic mass (suggestive of an extra-ovarian origin). If no ovarian parenchyma is visible, we should look for the ovarian pedicles to find the location of ovarian fossae and verify if the ovarian pedicle is adjacent to the mass. That’s why the MR protocol should include an anatomical lombo-pelvic sequence with slices from the mid-kidneys to the pubal symphysis which is best performed with a T2W sequence. Moreover, a sagittal T2W sequence is recommended to evaluate the mass and its relationship with the uterus. At the end, when a tubal origin is suspected, coronal views in T2WI are useful to confirm this hypothesis.

The absence of solid tissue is a main feature to suggest a low risk of malignancy (<5%) (Thomassin-Naggara et al. 2013). By definition,

a solid tissue enhances after gadolinium injection but any internal enhancement does not always correspond to solid tissue. Indeed, smooth septa are not considered as solid tissue. This feature is included in the expression “solid component” but not considered as solid tissue. Thus, a solid component groups unenhanced elements, such as clots and debris, and enhanced tissue including smooth septa and solid tissue. Solid tissue corresponds to irregular septa, solid papillary projection­ (>3 mm), mural nodule, and purely solid mass.

In our experience, unilocular cyst with solid tissue with a simple fluid content, or endometriotic contents or fatty contents have a very low risk of malignancy (<2%). A unilocular cyst with another type of fluid content has also a low risk of malignancy (<5%).

A bior a multilocular cyst without solid tissue again has a low risk of malignancy (<5%).

When a solid tissue is detected, the analysis of T2W signal, DW signal, and DCE MR signal within the solid tissue is useful. A solid tissue in low T2W signal and low DW signal has a very low risk of malignancy (<2%) (Thomassin-Naggara et al. 2013). If a solid tissue displays either an intermediate T2W signal or a high signal on DW sequence, time intensity curves comparing solid tissue to adjacent external myometrium are useful (Thomassin-Naggara et al. 2013). If the solid tissue enhances according to a type 1 time intensity curve, the PPV of malignancy is <5%. If the solid tissue enhances according to a type 3 time intensity curve, the PPV of malignancy is higher than 95%. If the solid tissue enhances according to a type 2 time intensity (ThomassinNaggara et al. 2013). In our experience, less than 15% of the lesions remain indeterminate. Thus, an MR classification has been developed named ADNEX MR Score which is under European validation (EURAD study) (Table 3).

3.2\ Step 2: Prediction

of the Histopathological

Diagnosis

If the first step is feasible by any junior radiologist or a general radiologist, this second step

Table 3  ADNEX MR score or EURAD score (Thomassin-Naggara et al. 2013)

A lesion with a solid tissue corresponds to MR categories 4, 5, and 6

a

c

requires deeper knowledge of functional and organic ovarian lesions. The analysis is based on the clinical history and the different MR parameters useful to analyze cystic and solid components characteristics, the shape, the wall, and the size of the lesion. Sometimes, the differentiation between functional and organic cysts is difficult and ultrasonographic follow-up helps to the make the differential diagnosis.

As for ultrasonography, we differentiate the following six categories of MR features:

MR pattern 1: Simple cyst

Simple cyst corresponds to a unilocular cyst lesion without internal enhancement with a fluid content that presents a low T1W signal, a high T2W signal, a low DW signal and a high ADC (Fig. 1). Nonspecific cyst, serous cystadenoma, follicular cyst, pseudo peritoneal cyst, and hydrosalpinx are usually classified in this pattern (Table 4).

b

Fig. 1  MR pattern 1: Serous benign cystadenoma (a: Axial T2W sequence, b: Axial T1W sequence, c: Axial T1W sequence after gadolinium injection). Step 1: Unilocular cyst without internal enhancement with a fluid

content in high T2W and low T1W signal corresponding to EURAD score 2. Step 2: There is no specific feature that helps to distinguish a functional cyst from an organic cyst

Table 4  Adnexal masses without solid tissue

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MR pattern 2: Nonsimple cyst

Nonsimple cyst corresponds to a unilocular cyst that has no internal enhancement with a fluid content that presents an intermediate or high T1W signal, a variable T2W signal, DW signal, and ADC maps. The analysis is based on the signal of the cystic content before and after fat suppression, the presence or the absence of wall enhancement, and the signal on the DW sequence (Table 4).

MR pattern 3: Multilocular cyst

In a multilocular cyst, there are smooth septa that enhance after gadolinium injection. Smooth septa are not considered as solid tissue. On T2W sequence, a luteal cyst with fibrinous component may look like a multilocular cyst. The difference between septa and fibrinous components is the presence of septal enhancement.

Septal enhancement is a key feature that helps to distinguish septa from fibrinous components that do not enhance after contrast media injection. In that case, the cyst can be considered as

unilocular indicating the luteal cyst. A lesion classified in this pattern “3” does not include any solid tissue.

MR imaging is useful in this group either in large lesion size or to characterize the cystic component owing to the combination of the different MR sequences to suggest a histopathological subtype. The different cystic fluid types found in ovarian tumors are:

––Mucin (moderate high T1W signal, intermediate T2W signal, high DW signal, high ADC value)

––Colloid (very low T2W signal, moderate high T1W signal)

––Blood (high T1W signal with and without fat suppression, intermediate T2W signal)

––Pus (moderate high T2W signal, intermediate T2W signal, high DW signal, low ADC value)

––Fat (high T1W signal that decreases after fat suppression) (Fig. 2)

MR pattern 4: Cyst with papillary projections

Fig. 2  MR pattern 3: Mature cystic teratoma (a: Axial T2W sequence, b: Axial T1W sequence, c: Axial T1W sequence with fat suppression, d: Axial T1W sequence with fat suppression after gadolinium injection). Step 1: Multilocular cyst without solid tissue with a fluid content

in high T2W, high T1W signal, and low T1 after fat corresponding to EURAD score 2. Step 2: The presence of fatty content and the absence of colloid suggests a teratoma. The absence of protuberance in this case strongly suggests a mature cystic teratoma

A papillary projection corresponds to solid tissue and centrally enhances after gadolinium injection (Fig. 3). This feature is important to distinguish a solid papillary projection from a small loculus before performing any time intensity curve (cause of false positive). Moreover, in tubal distension

pseudopapillary projections with the same size, regularly located on the cystic wall, indicate the cogwell sign (Ghattamaneni et al. 2009). A tubular shape in another plan may help to diagnose hydrosalpinx. Final differential diagnosis is a clot that does not enhance after gadolinium injection.

Fig. 3  MR pattern 4: Serous benign cystadenoma (a: Axial T2W sequence, b: Axial T1W sequence, c: Axial T1W sequence with fat suppression after gadolinium injection, d: Axial DWI sequence, e: Axial DCE MR sequence). Step 1: Unilocular cyst with solid tissue that corresponds to solid papillary projection that displays a

high T2W signal, low DW signal, and enhances according a TIC type 1 corresponding to EURAD score 3 (probably benign). Step 2: Unilocular cyst with papillary projection higher than 1 mm suggests a serous cystadenoma. Benign characteristics suggest a benign serous cystadenoma

The presence of solid papillary projections is pathognomonic of the presence of epithelial tumors but is not synonymous of a borderline or benign lesion. There are two main types of solid papillary projections:

––Larger than 1 mm in size found in serous cystadenomas which displays in benign lesion a

low T2W and low DW signal and a type 1 time intensity curve (TIC) and displays in borderline cystadenomas an intermediate T2W signal, a high DW signal and a type 2 TIC (Fig. 4).

––Smaller than 1 mm found in borderline mucinous cystadenomas. No papillary projection is

Fig. 4  MR pattern 4: Borderline serous cystadenoma (a: Axial T2W sequence, b: Axial T1W sequence, c: Axial T1W sequence with fat suppression after gadolinium injection, d: Axial DWI sequence, e: Axial DCE MR sequence). Step 1: Unilocular cyst with solid tissue that corresponds to grouped solid papillary projections that

display a high T2W signal, high DW signal, and enhances according a TIC type 2 corresponding to EURAD score 4 (indeterminate). Step 2: Unilocular cyst with papillary projection higher than 1 mm suggests a serous cystadenoma. Suspicious characteristics suggest a borderline serous cystadenoma

found in benign mucinous cystadenoma that displays only smooth septa.

In this pattern, only unilocular or multilocular cyst with solid papillary projections and no other type of solid tissue is present (see below in pattern 5).

When solid papillary projections are grouped, the distinction with a mural nodule can be difficult. This is important to distinguish a borderline cystadenoma (with solid papillary projections) from invasive malignant cystadenocarcinoma (mural nodule) when this tissue displays an intermediate T2W signal, a high DW signal, and a type 2 TIC. A mural nodule (or “solid portion”) corresponds to a pathological thickening of the wall due to malignant proliferation and thus an

obtuse angle with the wall is seen. In contrast, a group of papillary projections has an acute angle with the wall.

MR Pattern 5: Mixed mass

This pattern corresponds to a large variety of tumors that includes both cystic and solid components (Fig. 5). The analysis of gadolinium enhancement helps identify tumors that truly ­display a solid portion (echoic cystic portion at ultrasonography may look like solid tissue). The differential diagnoses are enlisted in detail in Table 5 and this category comprises the largest number of diagnoses. MR imaging is also useful to determine the origin of the tumor and may help to recognize a non-ovarian mass.

Fig. 5  5 MR pattern 5: Invasive cystadenocarcinoma (a: Axial T2W sequence, b: Axial DW sequence, c: Axial T1W sequence with fat suppression after gadolinium injection, d: Axial DCE MR sequence). Step 1: Mixed mass with solid tissue that corresponds to mural nodule

that displays intermediate T2W signal, high DW signal, and enhances according a TIC type 2 corresponding to EURAD score 4. Step 2: The morphology, the age of the patient (65-year-old woman), and the suspicious findings suggest an invasive cystadenocarcinoma

MR Pattern 6: Purely solid mass

The initial finding is an enlarged ovary due to an ovarian edema that induces an intermediate T2W signal, a high DW signal, and a variable enhancement. Follicles are located in the periphery of the ovary. The different causes of ovarian edema are detailed in Table 5.

Table 5  Adnexal masses with solid tissue

When there is a solid mass, the first question to answer is the origin of the lesion. The most common ovarian solid tumor is fibrothecoma, with the differential diagnosis of uterine leiomyoma which is the most frequent parauterine mass. The other diagnosis are neurogenic tumors such as schwannoma (main feature: anterior displace-

ment of posterior peritoneum), GIST tumor (main feature: intense homogeneous enhancement with cystic changes in the center part of the lesion), and pelvic lymph nodes (main feature: perivascular).

When the lesion is originating from the ovary, MR criteria are accurate to differentiate benign

from malignant tumors but less reliable for tissue characterization (Fig. 6). In this pattern, clinical history, biological markers, and CT scan are useful (Table 5). CT scan may help to detect calcifications which are suggestive of ovarian leiomyoma if they are coarse or suggestive of Brenner tumor if they are amorphous and central.

a

c

Fig. 6  MR pattern 6: Lymphoma (a: Axial T2W sequence, b: Axial DWI sequence, c: Axial DCE MR sequence). Step 1: Bilateral purely solid masses that display an intermediate T2W signal, high DW signal, and enhance according a TIC type 3 corresponding to EURAD

b

score 5 (probably malignant). Step 2: The morphology and the score suggest invasive malignancy. The bilaterality and the age of the patient (45-year-old woman) suggest either hematological disorder or ovarian metastasis