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Imaging-Based Classification of Adenomyosis: History
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Contributor: Sun-Wei Guo , Giuseppe Benagiano ,
Marc Bazot

Adenomyosis is a complex and poorly understood gynecological disease. Its diagnosis is carried out increasingly by imaging techniques, including transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI). However, the lack of a consensus on a classification system hampers relating imaging findings with disease severity or with the histopathological features of the disease, making it difficult to properly inform patients and clinicians regarding prognosis and appropriate management, as well as to compare different studies.

  • adenomyosis
  • elastography
  • fibrosis

1. The Tower of Babel

Featuring the presence of endometrial glands and stroma within the myometrium [1], adenomyosis is a uterine disease that affects many women of reproductive age and contributes to dysmenorrhea, pelvic pain, abnormal uterine bleeding (AUB)/heavy menstrual bleeding (HMB), and subfertility [2][3][4][5]. Consequently, it impacts negatively on the quality of life of the afflicted woman [6]. It is also associated with increased risk of several adverse pregnancy outcomes [3][7]. Due largely to its poorly understood pathogenesis and pathophysiology, its clinical management still poses a challenge [8] and will remain problematic until its various features can be linked to specific clinical symptoms, a difficult task because the symptoms of adenomyosis are not pathognomonic.
Dysmenorrhea, pelvic pain, AUB/HMB, and subfertility/infertility have been reported in 90.8% of affected women [9]; however, these conditions are unfortunately not specific to adenomyosis, and, as such, the diagnosis has to rely on other means [10]. The diagnosis of adenomyosis used to be determined solely by histology after hysterectomy, and, as such, it was found disproportionately in older, parous or perimenopausal women, with a prevalence ranging wildly from 10% to 88% [11]. With the advent of modern imaging technology, adenomyosis is increasingly diagnosed in a non-invasive fashion [12][13]. In the last three decades, transvaginal ultrasonography (TVUS) and magnetic resonance imaging (MRI) have gradually taken over the role of the post-hysterectomy histological evaluation as the principal diagnostic tool, and become the major diagnostic tools for adenomyosis.
For this reason and given the wild variation of adenomyosis in terms of location, pattern, size, and affected area, the one pressing issue is to classify the disease based on imaging diagnosis. Ideally, an established classification system should link the extent of the disease with symptoms, their severity, and/or prognostic indices [14][15][16]. It also should help to understand the pathogenesis, pathology, clinical manifestations of adenomyosis, suggest the best treatment modality, provide a prognosis, and if at all possible be capable of monitoring treatment response. Finally, since adenomyosis is still an under-investigated disease, a widely accepted classification system should allow improved comparisons of research data and clinical outcomes [17][18].
Due to these pressing needs, several image-based classification systems have been proposed [5][14][15][19][20][21][22] and summarized [23], but so far, no consensus has been reached. Recognizing the importance of an agreed classification, available information has been condensed in a number of reviews published over the last 15 years [5][15][16][23][24] and renewed efforts have been made towards a non-invasive ultrasound classification [25]. Unfortunately, so far, consensus has not been reached and without a consensus classification system, there is a real danger of repeating the catastrophic fiasco of building the Tower of Babel.

2. Imaging-Based Classification of Adenomyosis

Some classification systems have already demonstrated their utility in helping to understand adenomyosis better. For example, the Kishi system has helped people to understand that intrinsic adenomyosis, lesions that are confined to the subendometrial layer without involving the outermost myometrium, is often associated with the history of iatrogenic uterine procedure [19]. In addition, intrinsic adenomyosis is often associated with HMB while extrinsic or external adenomyosis is associated with pain [26].
Recently, Exacoustos et al. investigated the relation between an ultrasound-based disease classification and symptoms [25]. Women with ultrasound diagnosis of diffuse adenomyosis were older and had heavier menstrual bleeding compared to those with focal disease, but, when it came to the severity of dyspareunia and dysmenorrhea, there was no statistically significant difference. In contrast, focal adenomyosis was associated with a higher percentage of infertility. Overall, no direct correlation between ultrasound depictions of the extent of the disease and symptoms was found. The authors speculate that this may be related either to co-existent pathology, or to a true lack of correlation between symptoms and disease extent. However, better statistically powered studies will be warranted before definitive conclusions can be reached [25].
Table 1 summarizes various proposals for imaging-based classifications of adenomyosis. One conspicuous feature shared by all these proposals is that all of them attempted to correlate various classification parameters with either possible pathogenesis, or symptomatology or its severity. However, none of these parameters has been shown to be linked with the histological features of endometriotic lesions [23].
Table 1. Imaging-based classifications of adenomyosis proposed so far.
Author(s) and Year of Publication Imaging Platform Proposed Classification Rationale Remarks
Kishi et al. (2012) [19] MRI Four subtypes:
I: intrinsic;
II: extrinsic;
III: intramural;
IV: indeterminate		 Based on Sampson’s observation as well as clinical observations Subtypes I and II appear to have different pathogenesis, symptomology, and severity
Van den Bosch et al. (2015) [27]
Revised in Harmsen et al. (2022) [21]
(The MUSA standard)		 TVUS Direct features:
Cysts, hyperechogenic islands, echogenic subendometrial lines and buds.
Indirect features:
Asymmetrical thickening, globular uterus, irregular JZ, fan-shaped shadowing, translesional vascularity, interrupted JZ.		 Based on expert consensus through several rounds of modified Delphi procedure A welcome step towards the establishment of standardized terminology, with the goal to build a uniformly accepted or validated system to diagnose or classify the severity of adenomyosis based on imaging findings.
Bazot and Darai (2018) [14] MRI Three subtypes:
-Internal
-External
-Adenomyoma		 Based on Sampson’s observation as well as clinical observations Different subtypes appear to have different pathogenesis, symptomatology, and severity
Gordts et al. (2018) [5] MRI/TVUS/hysteroscopy Important parameters to be included in a classification system: Affected area (inner or outer myometrium), localization (anterior, posterior, or fundus), pattern (diffuse or focal), type (muscular or cystic), volume or size (expressed as <1/3, <2/3, >2/3 or in cm) These parameters are potentially related to symptomatology and/or severity Included parameters are important for accurate diagnosis and, through grading, may be associated with disease severity.
Van den Bosch et al. (2019) [28] TVUS Location (anterior, posterior, left or right lateral side, or fundus), differentiation (focal, diffuse, or mixed type), cysticity (cystic or non-cystic), uterine layer involvement (
I: involving inner/sub-endometrial myometrium;
II: involvement of middle myometrium;
III: involvement of outer/sub-serosal myometrium), extent (<1/4, ≥1/4 but ≤1/2, >1/2 myometrium), and size.		 Based on consensus among sonographers, and consistent with the previous MUSA consensus. A welcome first step towards an internationally accepted classification and reporting system
Kobayashi and Matsubara (2020) [20] MRI Five main categories: (1) affected area (internal vs. external), (2) pattern (diffuse, focal); (3) size (<1/3, <2/3, or >2/3 of uterine wall); and (4) localization (anterior, posterior, left lateral, right lateral, and fundus); (5) concomitant pathologies (none, PE, OE, DE, UF, others) Adopted from previous proposals of classification Combined all important features of adenomyosis that may be useful for proper classification
Exacoustos et al. (2020) [25] TVUS Type (focal, diffuse, or adenomyomas),
Extension of the lesion in the myometrium		 Empirical observations These variables seem to correlate with the severity of symptoms and infertility
Abbreviations used in the table: DE: deep endometriosis; JZ: junctional zone; MRI: magnetic resonance imaging; OE: ovarian endometrioma; PE: peritoneal endometriosis; UF: uterine fibroids.
All imaging classification systems proposed so far [5][14][15][19][20] are sensible. For example, part of Bazot and Darai’s system [14] as well as that of Kishi’s [19] can be traced back to the original Sampson’s grouping according to the origin or pathogenesis: invasion from within the uterus (arising from the uterine inner myometrial layer); invasion from outside the uterus (arising from the uterine outer myometrial layer); and misplaced endometrial tissue in the uterine wall (possibly arising from embryologically, solitary pluripotent Müllerian remnants) [14][20][29]. The intrinsic/internal type of adenomyosis also makes sense, since as early as 1908 Cullen was able to establish the physical continuity between eutopic and ectopic endometrium in many patients with adenomyosis [16][30]. This is demonstrated, using modern technology, by 3D rendition showing that adenomyosis lesions are stereoscopically characterized by an “ant colony-like network” that connects directly with endometrial glands [31].
These proposed classification types are a welcome step towards a homogenized system so that all gynecologists may speak the same language while some of them have been shown to be useful in separating different phenotypes. However, none of them has been shown to be able to stage adenomyosis, to correlate the severity of symptomology or have prognostic value. At best, a filing system can be established, upon which a patient could be classified into one of the classification categories, as shown recently [32].

This entry is adapted from the peer-reviewed paper 10.3390/jcm12010287

References

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