Adenomyosis

Abstract

Adenomyosis is defined as a benign invasion from the endometrium into the myometrium, producing a diffuse increase in the uterus, showing under a microscope non-neoplastic endometrial glands and stroma surrounded by hypertrophic and hyperplastic myometrium [1]. Siegler and Camilien [2] define adenomyosis as the presence of endometrial and corium glandular cells on more than 2.5 mm from the endometrium-myometrium interface.

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Definition and Clinical Findings

Adenomyosis is defined as a benign invasion from the endometrium into the myometrium, producing a diffuse increase in the uterus, showing under a microscope non-neoplastic endometrial glands and stroma surrounded by hypertrophic and hyperplastic myometrium [1]. Siegler and Camilien [2] define adenomyosis as the presence of endometrial and corium glandular cells on more than 2.5 mm from the endometrium-myometrium interface.

Adenomyosis affects women over age 30, predominantly from 40-50. It usually manifests clinically with dysmenorrhea, dyspareunia, and menometrorrhagia, which are nonspecific symptoms that are also common in other pelvic conditions, such as myoma, endometriosis, endometrial polyps, and dysfunctional uterine bleeding [3, 4]. The physical examination only shows positive findings when there is already an increase in uterine volume [3, 4].

The prevalence of adenomyosis, according to a hysterectomy series published in the literature, varies from 5% to 70% [5]. This great variation occurs to a large extent because there is no correlation between the histological parameters used by pathologists for this diagnosis [5]. In the same uterus, incidence varied between 31% and 62%, depending on the number of biopsies that were performed [1]. The risk factors for adenomyosis are a) previous hysteroscopic surgery, and b) multiparity [6].

For many years, the diagnosis of adenomyosis was found only in the hysterectomy after surgery, usually in patients in their 30s and 40s who were symptomatic and most of the time with constituted offspring [7]. The introduction of imaging methods in the study of the pelvis allows an earlier diagnosis of adenomyosis, with excellent accuracy, and has brought with it the prospect of evaluating its impact on clinical symptoms, including infertility [8].

The relationship between adenomyosis and infertility has been much researched nowadays, due to frequent findings of adenomyosis in younger patients, and is often associated with endometriosis and infertility [8, 9]. More recent studies have shown concordance between adenomyosis and endometriosis, from 27% and even up to 70% of the cases [8, 10]. Changes in uterine peristalsis are considered one of the hypotheses of the pathophysiology of adenomyosis, and can also be one of the causes of infertility, due to irregular transport of gametes [9].

Classification

From the pathological point of view, adenomyosis can be classified as superficial (when it reaches the inner third of the myometrium), or deep (when it reaches the two outermost thirds of the myometrium) [11]. It is classified as diffuse if it affects all the walls of the uterus, and focal when it only affects a wall. For the diffuse one, the differential diagnosis is done with uterine myomatosis, and the focal form (adenomyomas) with the myomas.

The association between adenomyosis and other uterine disease is quite common. In a study, the association with other pelvic abnormalities was present in 82.5% of the cases [12]. In another publication, concomitance with uterine fibroids was seen in 38.5%, and with endometrial hyperplasia in 30.8% of the cases that were studied [13].

Image Findings

Pelvic imaging methods used for diagnosis are both transvaginal ultrasonography and magnetic resonance imaging. Both methods are dependent on the examiners, and MR today is considered the method of choice in cases of clinical suspicion [3, 14, 15]. It has a sensitivity of 70–86% and a specificity of 86–93% [3].

For the diagnosis of adenomyosis on ultrasound, it is very important that the examiner pay attention to clinical information. A brief anamnesis, therefore, should always be performed. Transvaginal ultrasound, when performed by an experienced examiner, can have great diagnostic accuracy with sensitivity rates of 65 % and specificity of 97.5% [3]. In a group of patients with endometrial menometrorrhagia, without endometrial changes or myomas, the rates obtained were 80.9% of sensitivity, 100% of specificity, and 82.6% of accuracy [3]. While in a group of unselected patients who would undergo hysterectomies, the sensitivity of ultrasound was only 38.4% [12].

Various image signals associated with adenomyosis are described in the literature, and it is common to find several of them concurrently. The most important are:

Indistinct Endometrial-myometrial Junction

The loss of definition in the endometrial-myometrial transition is the characteristic sign of adenomyosis [5] (Fig. 7.1). Whether in focal areas or in a diffuse way, the presence of this uncertainty is an important parameter for the diagnosis (Figs. 7.2 and 7.3). The precise classification of the endometrium can be difficult in these situations, sometimes simulating endometrial thickening [1] (Figs. 7.4 and 7.5). MRI can confirm the diagnosis [3] (Fig. 7.6 a, b).

Fig. 7.1

Transvaginal sagittal image of the uterus shows heterogeneous echotexture in which the border from the endometrium is diffusedly blurred with respect to the myometrium

Fig. 7.2

Transvaginal sagittal image of the uterus shows heterogeneous echotexture in focal area at anterior wall where the edge of the endometrium is difficult to distinguish sonographically from the adjacent myometrium

Fig. 7.3

Transvaginal sagittal image of the uterus shows heterogeneous echotexture with poor definition of endometrium myometrial junction diffusedly

Fig. 7.4

Transvaginal sagittal image of the uterus shows heterogeneous myometrium appearance, especially on the posterior wall where hyperechoic areas with cysts mimic endometrial thickening

Fig. 7.5

Transvaginal sagittal image of the uterus shows heterogeneous myometrium appearance in focal area at posterior wall where hyperechoic areas with cysts mimic endometrial focal thickening

Fig. 7.6

(a) Transvaginal ultrasonography. In the fundus, an area of focal heterogeneity can be seen, without significant volume or morphology changes. (b) Sagittal, TSE, T2 weighting. The area identified in the fundus corresponds to a focal thickening of the junctional zone (arrowheads). There is also a uterine myoma (arrow) that was also identified in the US

Increase in Uterine Volume

Adenomyosis is a common cause of increased uterine volume [16]. Usually, the body is enlarged and presents a rounded shape − that is, it acquires a globular aspect [3] (Figs. 7.7, 7.8 and 7.9). This aspect, in the absence of focal lesions, is closely associated with adenomyosis, and for some authors it is considered a parameter with high sensitivity indexes for the diagnosis [13, 14].

Fig. 7.7

Transvaginal sagittal image shows a globular-appearing uterus, mottled heterogeneous texture, and small cystic area

Fig. 7.8

Transvaginal sagittal image shows a globular-appearing uterus. The shape of the uterine fundus was rounded and more spherical in configuration without focal lesions

Fig. 7.9

Coronal oblique, TSE, T2 weighting. Apart from the thickening and heterogeneity of the myometrium, endometrial striations, which are adenomyosis characteristics, can also be identified (arrows). A small myoma (arrowhead) and volumetric increase can be identified as well

Asymmetrical Thickening of the Uterine Walls

Disproportion between the thickness of the uterine walls (anterior and posterior), is usually associated with adenomyosis [11] (Figs. 7.10, 7.11, 7.12, and 7.13). For some authors, this signal can increase the method specificity [12].

Fig. 7.10

Sagittal, TSE, T2 weighting. In this case, a diffusely low myometrium signal can be observed, secondary to the thickening of the junctional zone with uterine volume increase and “globular” morphology, secondary to the asymmetry of the body walls promoted by a reactional hypertrophy of the myometrium

Fig. 7.11

Transvaginal sagittal image shows a globular asymmetric uterus (the posterior wall is enlarged with respect to anterior) and heterogeneous myometrium without leiomyomas

Fig. 7.12

Transvaginal sagittal image shows a globular asymmetric, enlarged uterus with the posterior wall enlarged with respect to the anterior, heterogeneous myometrium, and poor definition of endometrium-myometrial junction

Fig. 7.13

Sagittal, TSE, T2 weighting. This figure also shows the engagement of the rear body wall by focal adenomyosis (arrows), with thickening of the junctional zone and asymmetry of the body walls

Heterogeneous Appearance of the Myometrium

One of the most frequent signs of adenomyosis is the heterogeneous appearance of the myometrium, usually characterized by predominantly hypoechoic areas that affect normal stratification. It was present in 84% of positive cases in a study of histopathological correlation [6] (Figs. 7.14, 7.15, 7.16, and 7.17). These heterogeneous areas, more hypoechoic, can be focal, with ill-defined margins or compromising the organ diffusely [4] (Figs. 7.18a, b, 7.19, and 7.20). It is very important to identify this textural change because it manifests itself even before the increase in uterine volume.

Fig. 7.14

Transvaginal sagittal image shows a uterus with markedly heterogeneous myometrium (indistinctly defined hypoechoic myometrial areas) and poor definition of endometrium myometrial transition diffusedly

Fig. 7.15

Transvaginal sagittal image shows a uterus with markedly heterogeneous myometrium and poor definition of endometrium myometrial transition in focal area of uterine fundus

Fig. 7.16

Transvaginal sagittal image shows a uterus with heterogeneous echotexture in focal area at anterior wall. Note the poor definition of the endometrium myometrial junction and the small cystic areas associated

Fig. 7.17

Transvaginal sagittal image shows a uterus with diffused heterogeneous echotexture. Note the hypoechogenicity, global appearance, and poor definition of the associated endometrium myometrial junction

Fig. 7.18

(a) Axial, TSE, T2 weighting. Signal of the myometrium diffusely reduced, secondary to the adenomyosis (arrows), with no significant associated increase in volume, compatible with original shape. (b) Axial, SE, T1 weighted, with fat saturation. Note the hyperintense foci promoted by hematic content, in the myometrial cysts (arrows)

Fig. 7.19

Coronal, TSE, T2 weighting. Note the focal thickening of the junctional zone, compatible with adenomyosis (arrows) involving both uterine walls

Fig. 7.20

Sagittal, TSE, T2 weighting. In this case, an adenomyosis focus can be observed in the anterior body wall, with body asymmetry by the greater volume in the anterior (arrow)

Cystic Myometrial Areas

The presence of anechoic areas, initially described as small intramiometrial lakes measuring between 1 and 3 mm, is associated with adenomyosis. When it was present, in the midst of heterogeneous myometrial areas, in patients without myomas or endometrial changes, it showed a diagnostic sensitivity of 81% in a study [17]. Currently called myometrial cysts, they are generally rounded, they are between 1 and 5 mm in size, and they are considered by some authors to be one of the most sensitive signs for the diagnostis of adenomyosis [3]. These cysts probably correspond to expansions of ectopic endometrial glands [13] (Figs. 7.21 and 7.22).

Fig. 7.21

Transvaginal transverse image of the fundus of the uterus shows a mottled heterogeneous appearance with a small cystic area in the posterior wall

Fig. 7.22

Transvaginal sagittal image of the uterus shows a mottled heterogeneous appearance with small cystic areas in the posterior and anterior wall (arrow)

MR shows rounded foci ranging from 2-7 mm in diameter, with an average of 3 mm, surrounded by myometrial tissue. It is considered the main direct signal in the diagnosis of adenomyosis. They can provide high signal on T1-weighted sequences, depending on the phase of the secondary cycle to micro-hemorrhages (Fig. 7.18 a, b).

Echogenic Endometrial Striations

In some cases of adenomyosis, sub-endometrial echogenic linear images are formed, such as striations, transversely crossing the myometrium (Figs. 7.23 and 7.24). The finding of these striations or sub-endometrial echogenic nodules and asymmetry in the thickness of the walls showed high specificity for the diagnosis of adenomyosis, when correlated with histopathologic study [12]. Even alone, the sub-endometrial striations were considered, in another study, as the parameter with better specificity indexes, positive predictive value, and the most useful one for the differential diagnosis of adenomyosis and other diseases, especially uterine fibroids [11]. In MR, they have less significance when compared with the thickness of the junctional zone and detecting of myometrial cysts [13] (Fig. 7.9).

Fig. 7.23

Transvaginal sagittal image of the uterus shows myometrial hyperechoic striations as a radiate pattern of thin hyperechoic line penetrating into the myometrium from the endometrium. The myometrium is heterogeneous with poor definition of the endometrium myometrial junction and small cysts associated

Fig. 7.24

Transvaginal sagittal image of the uterus shows myometrial hyperechoic striations more evident in the posterior wall (arrows)

Thickening of the Junctional Zone

A thickness of more than 12 mm is considered to be the most accepted criterion in the diagnosis of adenomyosis by MR, with an accuracy of 85% and specificity of 96%.

Uterine zonal anatomy was originally described by Hricak et al [18] in 1983, evidencing a signal hypointense band with the endometrium, which was called “junctional zone.” It presents myocytes with a different morphology than other myometrial portions in its constitution, with a large nuclear area, and little extracellular matrix with a consequent small amount of water, reducing the signal on T2 weighted sequences. The concentric arrangement of myometrial fibers in the inner portion of the myometrium also adds to this (Fig. 7.10).

The junctional zone can vary according to age; it is thin in the pubarche patient, and more difficult to define in elderly patients who are post-menopausal, due to progressive loss of hydration of the outer myometrial layer, hence reducing its signal. It can also vary according to the menstrual cycle, reaching its peak during the menstrual period; some authors indicate performing MR in the ploriferative-secretorial final phase in order to increase sensitivity [18]. Its value, when regarded as normal, is less than 12 mm, with a median between 5 and 8 mm (Fig. 7.19).

Two other parameters are related to the extent of the junctional zone. The first is called junctional zone differential, described by Dueholm et al. [19] in 2001. It is calculated by the difference between the maximum and the minimum thickness of the anterior and posterior portions of the uterus. Its validity has yet to be proven, and it is not routinely used in practice. The other signal, known as ratio of junctional zone thickness and miometrial thickness, has already been rated by Bazot et al. [3], and its accuracy is not statistically better than the simple measurement of 12 mm in the true sagittal cut of sequences weighted in T2 [4, 14].

Additional Magnetic Resonance Imaging Parameters

Contrast

Adenomyosis is most often a diffuse disease of the myometrium, it presents enhancement with inespecific patterns. Because of this, contrast use is unnecessary in most cases.

Diffusion

Focal malignant lesions typically have low ADC values, and the benign ones tend to have low values. However, high levels of ADC may be found in hemorrhages and necrosis. They can be used as a complementary tool to differentiate sarcomas of degenerated myomas, because myomas with degeneration tend to have a higher ADC, and lower signal than sarcomas. ADC and diffusion parameters with statistical significance for adenomyomas have not yet been found.

Cine-MRI

The dynamic images from Cine-MRI allow the differentiation between uterine contraction and focal adenomyosis in most of the cases. However, they are not widely used in clinical practice, because it consumed time and having been sucefully replaced by a another sagital T2 sequence, performed in the end of exam.

Differential Diagnosis

Focal Adenomyosis and Myoma

There are two types of focal adenomyosis: (a) when the disease affects a single uterine wall, or (b) when it has a pseudo-nodular feature, such as a rounded hypoechoic area, or inaccurate boundaries in relation to the adjacent myometrium, known as “adenomyoma” [20]. The adenomyoma is often confused with fibroids, and both can have the same clinical presentation. Fibroids can be surgically excised (myomectomies), while the definitive surgical treatment for adenomyomas is hysterectomy. This accurate differential diagnosis is very important, especially in patients who want to preserve fertility and will be subject to myomectomies or treatment with GnRH analogues [3].

Adenomyomas usually have ill-defined margins, while myomas are more circumscribed, with better defined edges [21, 22] (Figs. 7.25a–c, 7.26, and 7.27). In the colored Doppler study, myomas often have characteristic peripheral vasculature surrounding their margins, while adenomyomas present vascularization in their center [16] (Figs. 7.28a, b, and 7.29a, b). The presence of cystic gaps is also more frequent in adenomyomas and may eventually be present in myomas with hyaline degeneration [4]. The use of colored Doppler in these cases is essential for the differential diagnosis (Figs. 7.30a, b, and 7.31a, b). Special attention should be given in cases of concurrence between myomas and adenomyomas.

Fig. 7.25

(a) Transvaginal ultrasonography. In this image, a nodule can be seen (arrow), which is poorly defined in a discreetly heterogeneous myometrium, with no flow to the amplitude Doppler. (b) Sagittal, TSE, T2 weighting. The node identified in the US is heterogeneous and has a cystic component (arrow) compatible with cystic adenomyosis. (c) Surgical piece. Myometrial nodulation with cysts in its interior, compatible with adenomyosis

Fig. 7.26

Transvaginal transverse image of the fundus of the uterus shows an adenomyoma (arrows) on the left wall and hypoechoic, poorly defined nodule

Fig. 7.27

Transvaginal oblique image of the uterus shows a myoma on the right wall and focal hypoechoic circumscribed nodule (arrow)

Fig. 7.28

Transvaginal oblique image of the uterus with a myoma on the fundus. (a) Grayscale shows focal hypoechoic circumscribed nodule. (b) Color Doppler sonogram shows vessels at the margin of the lesion

Fig. 7.29

Transvaginal oblique image of the uterus. (a) Grayscale shows adenomyoma on the fundus (arrows). (b) Color Doppler sonogram of the same image shows the presence of straight vessels traversing a hyper-trophic myometrium

Fig. 7.30

Transvaginal oblique image of the uterus. (a) Grayscale shows adenomyoma on the dorsal left aspect of the uterus with central cystic area that can simulate a degenerated myoma. (b) Color Doppler sonogram of the same image shows the presence of straight vessels traversing a hyper-trophic myometrium

Fig. 7.31

Transvaginal transverse image of the uterus. (a) Grayscale shows a degenerated myoma as a well-circumscribed nodule with central cystic area. (b) Color Doppler sonogram of the same image shows the presence of straight vessels traversing a hyper-trophic myometrium

The adenomyoma, as well as the myoma, has low signal intensity on T2; however, the adenomyoma usually has small, hyperintense foci in T2, without large vessels identified on its periphery [23]. The cases of cystic adenomyoma correspond to excessive ectopic endometrial tissue, which produces focal hemorrhage. The lesion usually presents a cystic cavity greater than 1 cm, with signal content compatible with hemorrhagic material in its interior, surrounded by fibrous tissue with low signal intensity on T2 [24] (Fig. 7.32).

Fig. 7.32

Sagittal, TSE, T2 weighting. Note the adenomyosis focus in the posterior wall (arrowheads) and an exophytic subserosal myoma in the anterior wall (arrows)

Adenomyosis and Endometriosis

Patients with endometriosis tend to have more severe pelvic pain than those with adenomyosis. Endometriosis is implanted in the uterine serous, and its involvement is unconventional, usually associated with the obliteration of a recto-uterine recess and impairment of the front walls of the rectum or posterior vaginal fornix. A local involvement of external fibers of the myometrium and serous are more characteristic of endometriosis with myometrial invasion than of adenomyosis, in most cases (Figs. 7.33 and 7.34).

Fig. 7.33

Sagittal, TSE, T2 weighting. Endometriosis, when it affects the myometrium, starts by the serous, promoting adherence hypointense foci, and obliterating the posterior compartment (arrows). The focal involvement by adenomyosis may be a differential; however, its characteristics are different due to the process starting in the junctional zone, which in this case is preserved

Fig. 7.34

Sagittal, TSE, T2 weighting. In this case there is a cyst (C) representing the cystic adenomyosis affecting the anterior body wall. Endometriosis adhesion bands in the rear compartment can also be noted (arrow)