Diagnosing adenomyosis: an integrated clinical and imaging approach

Abstract

BACKGROUND Adenomyosis is a benign uterine disorder where endometrial glands and stroma are pathologically demonstrated within the uterine myometrium. The pathogenesis involves sex steroid hormone abnormalities, inflammation, fibrosis and neuroangiogenesis, even though the proposed mechanisms are not fully understood. For many years, adenomyosis has been considered a histopathological diagnosis made after hysterectomy, classically performed in perimenopausal women with abnormal uterine bleeding (AUB) or pelvic pain. Until recently, adenomyosis was a clinically neglected condition. Nowadays, adenomyosis may also be diagnosed by non-invasive techniques, because of imaging advancements. Thus, a new epidemiological scenario has developed with an increasing number of women of reproductive age with ultrasound (US) or magnetic resonance imaging (MRI) diagnosis of adenomyosis. This condition is associated with a wide variety of symptoms (pelvic pain, AUB and/or infertility), but it is also recognised that some women are asymptomatic. Furthermore, adenomyosis often coexists with other gynecological comorbidities, such as endometriosis and uterine fibroids, and the diagnostic criteria are still not universally agreed. Therefore, the diagnostic process for adenomyosis is challenging. OBJECTIVE AND RATIONALE We present a comprehensive review on the diagnostic criteria of adenomyosis, including clinical signs and symptoms, ultrasound and MRI features and histopathological aspects of adenomyotic lesions. We also briefly summarise the relevant theories on adenomyosis pathogenesis, in order to provide the pathophysiological background to understand the different phenotypes and clinical presentation. The review highlights the controversies of multiple existing criteria, summarising all of the available evidences on adenomyosis diagnosis. The review aims also to underline the future perspective for diagnosis, stressing the importance of an integrated clinical and imaging approach, in order to identify this gynecological disease, so often underdiagnosed. SEARCH METHODS PubMed and Google Scholar were searched for all original and review articles related to diagnosis of adenomyosis published in English until October 2018. OUTCOMES The challenge in diagnosing adenomyosis starts with the controversies in the available pathogenic theories. The difficulties in understanding the way the disease arises and progresses have an impact also on the specific diagnostic criteria to use for a correct identification. Currently, the diagnosis of adenomyosis may be performed by non-invasive methods and the clinical signs and symptoms, despite their heterogeneity and poor specificity, may guide the clinician for a suspicion of the disease. Imaging techniques, including 2D and 3D US as well as MRI, allow the proper identification of the different phenotypes of adenomyosis (diffuse and/or focal). From a histological point of view, if the diagnosis of diffuse adenomyosis is straightforward, in more limited disease, the diagnosis has poor inter-observer reproducibility, leading to extreme variations in the prevalence of disease. Therefore, an integrated non-invasive diagnostic approach, considering risk factors profile, clinical symptoms, clinical examination and imaging, is proposed to adequately identify and characterise adenomyosis. WIDER IMPLICATIONS The development of the diagnostic tools allows the physicians to make an accurate diagnosis of adenomyosis by means of non-invasive techniques, representing a major breakthrough, in the light of the clinical consequences of this disease. Furthermore, this technological improvement will open a new epidemiological scenario, identifying different groups of women, with a dissimilar clinical and/or imaging phenotypes of adenomyosis, and this should be object of future research.

Prevalence of adenomyosis in endometrial cancer patients: a systematic review and meta-analysis

“…Adenomyosis is a common benign gynecologic condition with variable clinical symptoms [15]. However, some studies suggest a potential association with EC [7,13,27,28].…”

“…First, the hyper-estrogenic state favors the spread into the myometrium of adenomyosis and, similarly, can promote endometrial cell proliferation and the development of estrogen-related endometrial cancer [2,14]. Second, adenomyosis is also considered an inflammatory disease secondary to auto-traumatization caused by peristaltic myometrial contraction [15]; likewise, chronic inflammatory condition with secretion of cytokines (Interleukin 6 and 8), chemokines and growth factors (e.g., vascular endothelial growth factor) can facilitate tumor development and dissemination [16,17]. Third, common mutations in the signaling pathway upregulating cellular proliferation have been found in both the diseases [31].…”

“…Several studies have assessed the histological co-existence of endometrial carcinoma (EC) and adenomyosis reporting different data [6][7][8][9][10][11][12][13]. The two pathologies share common etiopathogenetic mechanisms including unopposed hyper-oestrogenic state, inflammatory milieu and molecular features favoring cell proliferation and inflammation [14][15][16][17][18][19][20]. According to some authors, adenomyosis could 1 3 promote EC and affect pathological factors impacting on EC prognosis [7,8,11].…”

Endometriosis Associated Infertility: A Critical Review and Analysis on Etiopathogenesis and Therapeutic Approaches

“…While endometriosis is a chronic inflammatory disease that involves the presence of extrauterine endometrial-like tissue, adenomyosis is a benign condition that occurs at the level of uterus, within the myometrium, being characterized by the presence of ectopic endometrial tissue glands and stroma in this area [ 91 , 92 ]. This particular condition is usually diagnosed while investigating with other gynecological comorbidities such uterine fibroids and endometriosis [ 92 , 93 , 94 ]. Several hypotheses have been proposed, but a common definition of adenomyosis remains controversial due to theories regarding the pathogenesis, diagnostic criteria, and classifications of this disease.…”

Differential Diagnosis of Endometriosis by Ultrasound: A Rising Challenge

“…Buds do not develop from endometrial hyperplasia, but instead they arise from an atrophic endometrium [ 33 ]. The age of onset, which largely overlaps [ 34 ], clinical presentation [ 35 ], and endometrial thickness (women with symptomatic adenomyosis or perimenopausal menstrual alterations are often on hormonal therapy) may not help in the DD; however, the myometrial vascularization may provide some clues. In adenomyosis cases, the vessel distribution (i.e., arcuate, radial, and basal arteries) within the myometrium and the lesion is not altered [ 19 , 32 ], whereas the neoangiogenesis that occurs in tumoral lesions is detected by color/power Doppler and the identification of aberrant vessels, even in cases of endometrial cancer in which the endometrium does not appear particularly irregular [ 36 ].…”