A New Classification of Benign, Premalignant, and Malignant Endometrial Tissues Using Machine Learning Applied to 1413 Candidate Variables.

Benign normal (NL), premalignant (endometrial intraepithelial neoplasia, EIN) and malignant (cancer, EMCA) endometria must be precisely distinguished for optimal management. EIN was objectively defined previously as a regression model incorporating manually traced histologic variables to predict clonal growth and cancer outcomes. Results from this early computational study were used to revise subjective endometrial precancer diagnostic criteria currently in use. We here use automated feature segmentation and updated machine learning algorithms to develop a new classification algorithm. Endometrial tissue from 148 patients was randomly separated into 72-patient training and 76-patient validation cohorts encompassing all 3 diagnostic classes. We applied image analysis software to keratin stained endometrial tissues to automatically segment whole-slide digital images into epithelium, cells, and nuclei and extract corresponding variables. A total of 1413 variables were culled to 75 based on random forest classification performance in a 3-group (NL, EIN, EMCA) model. This algorithm correctly classifies cases with 3-class error rates of 0.04 (training set) and 0.058 (validation set); and 2-class (NL vs. EIN+EMCA) error rate of 0.016 (training set) and 0 (validation set). The 4 most heavily weighted variables are surrogates of those previously identified in manual-segmentation machine learning studies (stromal and epithelial area percentages, and normalized epithelial surface lengths). Lesser weighted predictors include gland and lumen axis lengths and ratios, and individual cell measures. Automated image analysis and random forest classification algorithms can classify normal, premalignant, and malignant endometrial tissues. Highest predictive variables overlap with those discovered independently in early models based on manual segmentation.

Endometrial hyperplasia and the risk of coexistent cancer: WHO versus EIN criteria.

Endometrial hyperplasia (EH) is classified into benign and precancerous according to two different histomorphological systems: the World Health Organisation (WHO) system (based on the subjective evaluation of cytological atypia) and the endometrial intraepithelial neoplasia (EIN) system (based on a combination of several parameters that are assessable subjectively, or objectively through computerised analysis). The American College of Obstetricians and Gynecologists recommends use of the EIN system. Nonetheless, a higher prognostic value for EIN criteria was demonstrated only with the objective assessment, which is not routinely applicable. The aim of this study was to evaluate which of the subjective classifications of EH (WHO or EIN) has better prognostic value, by assessing the risk of coexistent cancer. Electronic databases were searched for relevant articles from the inception of the databases to July 2018. All studies assessing the presence of cancer on hysterectomy specimens after a preoperative histological diagnosis of EH were included. Odds ratios (ORs), sensitivity and specificity were calculated with 95% confidence intervals (CIs). Sixteen cohort studies and three case-control studies, assessing 2582 EHs, were included. The WHO criteria showed an OR of 11.15 (95% CI 7.65-16.24), a sensitivity of 0.86 (95% CI 0.82-0.90) and a specificity of 0.67 (95% CI 0.64-0.70) for coexistent cancer. The subjective EIN system showed a similar OR (11.85, 95% CI 4.91-28.62; P = 0.90), higher sensitivity (0.98, 95% CI 0.94-0.99), and lower specificity (0.29, 95% CI 0.24-0.34). The WHO system and the subjective EIN system have similar prognostic values. However, the EIN criteria appear to be more sensitive and thus more suitable for selecting women who need to be treated, whereas the WHO criteria, based on cytological atypia, seem to be more specific for lesions at higher risk of cancer. Therefore, integration of the EIN system with cytological atypia should be considered.

Guideline No. 390-Classification and Management of Endometrial Hyperplasia.

OBJECTIVE: The aim of this guideline is to aid primary care physicians and gynaecologists in the initial evaluation of women with suspected endometrial hyperplasia, to recommend the use of the 2014 World Health Organization classification for endometrial hyperplasia by all health care providers, and to guide the optimal treatment of women diagnosed with endometrial hyperplasia. INTENDED USERS: Physicians, including gynaecologists, obstetricians, family physicians, general surgeons, emergency medicine specialists; nurses, including registered nurses and nurse practitioners; medical trainees, including medical students, residents, and fellows; and all other health care providers. TARGET POPULATION: Adult women (18 years and older) presenting with suspected or confirmed endometrial hyperplasia. OPTIONS: The discussion relates to the medical therapy as well as surgical treatment options for women with and without atypical endometrial hyperplasia. EVIDENCE: For this guideline, relevant studies were searched in PubMed, Cochrane Wiley, and the Cochrane Systematic Reviews using the following terms, either alone or in combination, with the search limited to English language materials, human subjects, and published since 2000: (endometrial hyperplasia, endometrial intraepithelial neoplasia, endometrial sampling, endometrial curettage, diagnosis) AND (treatment, progestin therapy, surgery, LNG-IUS, aromatase inhibitors, metformin ), AND (obesity). The search was performed in April 2018. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 2152, and 82 studies were included in this review. VALIDATION METHODS: The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework. The interpretation of strong and weak recommendations was also included. The Summary of Findings is available upon request. BENEFITS, HARMS, AND/OR COSTS: It is expected that this guideline will benefit women with endometrial hyperplasia. This should guide patient informed consent before both medical and surgical management of this condition. GUIDELINE UPDATE: Evidence will be reviewed 5 years after publication to decide whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations. SUMMARY STATEMENTS: RECOMMENDATIONS.

Endometrial hyperplasia and progression to cancer: which classification system stratifies the risk better? A systematic review and meta-analysis.

PURPOSE: Benign and precancerous endometrial hyperplasias (EH) are differentiated thorough two possible histomorphologic classifications: WHO (adopting the subjective evaluation of cytologic atypia) and EIN (adopting several histomorphologic parameters, evaluable subjectively, or objectively with a computerized analysis calculating a prognostic score, the D score). ACOG recommends the use of EIN system although no distinction was made between objective assessment (not widely available), and subjective assessment (more applicable in the common practice). Moreover, it is still unclear if subjective EIN system is actually preferable to WHO classification. We aimed to assess the reliability of WHO system, D score and subjective EIN system in stratifying the risk of progression to cancer in EH. METHODS: MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, Cochrane Library and Google Scholar were searched for relevant articles from the inception to August 2018. All studies assessing the rates of progression of EH to cancer were included. RESULTS: Twelve cohort studies and one case-control study, assessing 3629 EH, were included. Relative risk (RR) for cancer progression was calculated with 95% confidence interval (CI), and results were compared using Chi-square test (significant p value < 0.05). WHO system showed a RR of 8.74 (95% CI 6.66-11.47). Objective D score showed a RR of 29.22 (95% CI 13.24-64.51), significantly higher than WHO (p = 0.005). Subjective EIN system showed a RR of 19.37 (95% CI 5.86-64.01), intermediate between WHO and D score, without significant differences (p = 0.20 and p = 0.57, respectively). CONCLUSION: Objective EIN criteria with D score are significantly more reliable than WHO criteria in stratifying the risk of progression of EH to cancer. Subjective EIN criteria did not show significant superiority over WHO instead. Further studies are necessary to determine if subjective EIN system should replace WHO system in the routine diagnosis of EH.

An audit of endometrial hyperplasias at the Lagos University Teaching Hospital.

INTRODUCTION: There has been much controversy and confusion surrounding the endometrial hyperplasias stemming from the use of a wide variety of terminologies and also from the pathophysiologic mechanisms underlying the various entities. The current classification by the World Health Organization (WHO) published in 2014 clarifies these issues. OBJECTIVE: The aim of this study, therefore, was to audit and standardize cases of endometrial hyperplasia diagnosed in our institution from 2007 to 2011. MATERIALS AND METHODS: The slides and request forms of cases diagnosed as endometrial hyperplasias at the Department of Anatomic and Molecular Pathology from January 1, 2007, to December 31, 2011 were retrieved, reviewed, and reported according to the WHO 2014 classification scheme. RESULTS: Hyperplasia without atypia accounted for the vast majority of cases (95.5%) and was the most common in the 5th decade. Concordance rates of 74.5% and 100% were found between endometrial hyperplasias without atypia and atypical hyperplasias with their previous diagnoses, respectively. CONCLUSION: The WHO classification scheme standardizes and simplifies the terminology used in the diagnosis of endometrial hyperplasias, while reflecting, at the same time, the current understanding of genetic changes that provide information necessary for prognostication and treatment.

[Pitfalls in the histopathological diagnostics of endometrial carcinoma and its precursors : Clinically relevant differential diagnoses, avoidance of false positive diagnoses]. / Fallstricke bei der histopathologischen Diagnostik des Endometriumkarzinoms und seiner Vorstufen : Klinisch wichtige Differenzialdiagnosen, Vermeidung falsch-positiver Diagnosen.

Making an incorrect histopathological diagnosis of an endometrial lesion may lead to unwanted loss of fertility and therapy-associated morbidity; therefore, endometrial carcinomas need to be correctly typed and differentiated from hyperplastic precursors, benign lesions and artifacts. Typical diagnostic pitfalls are described in this article. Misdiagnosing endometrial lesions can be avoided by paying thorough attention to gross as well as microscopic features and by taking crucial differential diagnoses into consideration. These are, in particular, well-differentiated endometrioid adenocarcinoma of the endometrium versus atypical endometrial hyperplasia, myoinvasive endometrioid adenocarcinoma versus atypical polypoid adenomyoma and endometrioid carcinoma versus serous carcinoma of the endometrium with a predominantly glandular pattern. It is also important to consider the possibility of a false positive diagnosis of atypical endometrial hyperplasia or carcinoma in cases of biopsy-induced artifacts.

Can malignant potential of endometrial polyps be determined by incorporating the endometrial intraepithelial neoplasia (EIN) classification?

OBJECTIVE: The reported frequency of malignant or premalignant changes confined to endometrial polyps (EP) is 0.5-6%. The management of atypical endometrial hyperplasia (AEH) confined to EP is not yet established. Recently, an alternative pathological nomenclature has emerged using the term endometrial intraepithelial neoplasia (EIN) instead of atypia. The objective of this study was to evaluate the safety of conservative hysteroscopic resection of endometrial polyps with AEH or EIN. METHODS: Retrospective cohort study of all cases of hysteroscopic resections of EP was performed at a single center between the years 2000-2011. All patients with a pathologic diagnosis of AEH in EP were included. A post-hoc revision of the pathologic specimens was made according to the EIN classification. RESULTS: Of the 32 patients with AEH in EP, 25 had normal endometrial curetting. Even with AEH confined to EP, 12 cases (48%) showed AEH (11 cases) or carcinoma (1 case) in the hysterectomy specimens. EIN in EP (14 cases) was correlated with 57% of diagnosis of EIN or carcinoma in the uterus; whereas in the absence of EIN in EP only 1 of 9 cases showed EIN in the final pathologic specimen (p=0.002), and none with carcinoma, which yields a PPV of 14% and a NPV of 100%. CONCLUSION: The diagnosis of EIN in EP may be a better predictor than AEH for endometrial involvement with malignant or pre-malignant neoplasms. The safety of conservative hysteroscopic resection of EP with AEH/EIN is questioned.

Management of "Atypical Endocervical Cells" Compared to "Atypical Glandular Cells".

OBJECTIVE: To assess adherence to management guidelines based on the terminology used to describe atypical glandular cells (AGC) on cytology reports. MATERIALS AND METHODS: We analyzed AGC pathology reports from Hartford Hospital, 2004-2007, and identified cases of AGC with the terminology atypical glandular cells or atypical endocervical cells (AEC). We calculated rates of clinical evaluations based on the terminology used to describe the AGC. Statistical analysis was performed using the χ test. RESULTS: Seventy-eight reports contained the terminology AEC and 97 reports contained the terminology AGC. The rate of histologic sampling in women with AEC was lower than in women with AGC (52.6% vs 83.5%; p < .01). Similarly, the rate of comprehensive evaluations was lower (33.3% vs 71.1%; p < .01). Fewer endocervical curettages (47.4% vs 77.3%; p < .01) and fewer endometrial biopsies in women 35 years or older were performed (26.9% vs 69.1%; p < .01) in women with AEC than in women with AGC. CONCLUSIONS: Women with AGC reports containing the term AEC were managed less optimally than those with AGC. These results suggest that the terminology used to describe the finding of atypical glandular cells may influence the clinical evaluation. Clinicians may not recognize AEC as AGCs. Ours results suggest that the terminology atypical endocervical cells should be avoided or accompanied by the terminology atypical glandular cells.

Reproducibility of current classifications of endometrial endometrioid glandular proliferations: further evidence supporting a simplified classification.

AIMS: To compare the reproducibility of the current (2003) World Health Organization (WHO), endometrial intraepithelial neoplasia (EIN) and European Working Group (EWG) classifications of endometrial endometrioid proliferations. METHODS AND RESULTS: Nine expert gynaecological pathologists from Europe and North America reviewed 198 endometrial biopsy/curettage specimens originally diagnosed as low-grade lesions. All observers were asked to classify the cases by using the categories described in each scheme: six for WHO, four for EIN, and three for EWG. The results were evaluated by kappa statistics for more than two observations. The analysis was repeated using only two major categories (benign versus atypical/carcinoma). Both the WHO and EIN classifications showed poor interobserver agreement (κ = 0.337 and κ = 0.419, respectively), whereas the EWG classification showed moderate agreement (κ = 0.530). Full agreement between pathologists occurred in only 28% for the WHO classification, 39% for the EIN classification, and 59% for the EWG classification. With only two diagnostic categories, kappa values increased in all classifications, but only the EWG classification reached a substantial level of agreement (κ = 0.621); similarly, full agreement among all pathologists increased to 70% for the WHO classification, 69% for the EIN classification, and 72% for the EWG classification. CONCLUSIONS: A two-tier classification of endometrial endometrioid proliferative lesions improves reproducibility, and should be considered for the diagnosis of endometrial biopsy/curettage specimens.

Endocervical glandular lesions exhibiting gastric differentiation: an emerging spectrum of benign, premalignant, and malignant lesions.

A variety of benign and malignant endocervical glandular lesions exhibiting gastric differentiation has been described in the past decade that has resulted in the concept of an important category of cervical adenocarcinoma which is unrelated to human papillomavirus (HPV). Both minimal deviation adenocarcinoma (MDA), also known as adenoma malignum, and the benign lesion lobular endocervical glandular hyperplasia (LEGH), have been known for some time to exhibit a gastric phenotype and immunophenotype (HIK1083 and/or MUC6 positive). Accumulated evidence suggests that a subset of LEGH (atypical LEGH) exhibits a degree of cytologic and/or architectural atypia which, in some cases, may be associated with and be a precursor of adenocarcinomas exhibiting gastric differentiation, including MDA. Gastric-type adenocarcinoma (GAS), a recently described subtype of cervical adenocarcinoma, is an emerging clinicopathologic entity. These neoplasms exhibit a spectrum of differentiation, including MDA as its very well-differentiated form, are unrelated to HPV, and exhibit aggressive clinical behavior. It is proposed that a LEGH-GAS sequence exists and, from a practical point of view, the development of optimal biomarkers is awaited to assist in early detection of GAS and atypical LEGH, as current HPV-targeted screening generally does not detect these lesions and strategies employing HPV vaccination will not prevent their occurrence. Pathologists should be familiar with the morphologic spectrum of these benign, premalignant, and malignant cervical glandular lesions exhibiting gastric differentiation. They are occasionally associated with Peutz-Jeghers syndrome or are a component of "synchronous mucinous metaplasia and neoplasia of the female genital tract."

Recommendation for the collection and analysis of endometrial biopsies for hormone therapies.

The assessment of endometrial safety is one of the key requirements for the clinical development of new products for hormone therapy (HT) to treat menopausal symptoms in women who have a uterus. Both the Food and Drug Administration (FDA) in the United States and the European Medicines Agency (EMA) provide detailed guidance on the requirements for the evaluation of biopsies to prove endometrial safety. However, there are some discrepancies between the European and the US requirements, making it difficult to fulfil both guidelines simultaneously. In order to facilitate multinational clinical trials performed within clinical programs to develop novel HT products, we developed an approach considering both guidance documents as far as possible and proposed solutions for issues that are inconsistently described in these guidelines. A table with the required sample sizes is given. Our recommendation for a unified approach for the estimation of the hyperplasia rate for hormone therapies fulfils the intent of the recommendations of both the FDA and the EMA and thus leads to a globally harmonized drug development for hormone therapies.

Molecular biomarkers in endometrial hyperplasias predict cancer progression.

OBJECTIVE: The purpose of this study was to assess the value of the 2003 World Health Organization (WHO) and endometrial intraepithelial neoplasia (EIN) classifications, D-score, and molecular biomarkers in endometrial hyperplasia (EH) for cancer progression. STUDY DESIGN: We conducted a review of 307 endometrial hyperplasias for WHO and EIN classifications and an analysis of biomarkers, D-score, and cancer progression-free survival. RESULTS: The WHO, EIN, D-score, and many biomarkers were prognostic; 7.2% of the samples progressed to cancer. The WHO and EIN classifications correlated weakly with CK5/6 and p16. The D-score was strongest prognostically. When >1, it had the lowest false-negative progression rate of all features analyzed. COX2 negativity was the only other independent multivariate cancer progression predictor in endometrial hyperplasia, but only in cases with D-score <1. Eight of 13 cases (61%), with a combined D-score of <1 and negative COX2 progressed, which contrasted with 3 of 139 of all other cases (2.8%) (P < .0001; hazard ratio, 53.0). The biomarkers did not strengthen the prognostic value of the WHO or EIN classification. CONCLUSION: Combined D-score <1 and COX2 negativity strongly predict cancer progression in endometrial hyperplasias.

Endometrial hyperplasia.

Endometrial hyperplasia is a heterogeneous set of pathologic lesions that range from mild, reversible glandular proliferations to direct cancer precursors. These lesions comprise a continuum of morphologic appearances, with the earliest proliferation represented by crowded glands with simple tubular architecture lined by cells resembling proliferative endometrium, whereas advanced proliferations in this continuum are characterized by crowded glands with complex architecture, often containing cells with nuclear atypia resembling low-grade endometrioid adenocarcinoma. The former "early" proliferations may be isolated to an endometrial polyp, but advanced proliferations are generally more diffusely present throughout the endometrium. There are at least three major classification systems for endometrial carcinoma precursor lesions, each of which trend toward overlap at the complex end of the spectrum. Although some classifications are based on a series of molecular genetic alterations (which may or may not translate into biologically or clinically relevant risk lesions), each classification scheme ultimately uses a series of histologic features, usually a combination of architecture and cytology, to establish a diagnosis of hyperplasia. Because different pathologists may apply different histologic criteria for endometrial hyperplasia depending on the classification system used, this article will provide an overview of the classifications used in current daily practice, present the histologic criteria and relative merits of each classification system, and discuss common and not so common causes of misclassification.

Management of endometrial hyperplasia.

Endometrial hyperplasia is a commonly seen clinical entity. A great majority of patients present with abnormal uterine bleeding. Unopposed estrogen either from an endogenous or exogenous source is the most important etiologic factor. Etiologic evaluation and cause specific treatment is a must for these patients instead of direct biopsies and treatments. Clinical importance of this pathological entity is the underlying risk of carrying a concomitant genital cancer and the potential risk of progression to endometrial carcinoma during the follow-up. Despite to a great effort on research and a long history of the disease in the medical literature; we still do not have a practical and accurate system available to use during daily practice in order to differentiate the real precancerous lesions. Treatment of endometrial hyperplasia depends on the patient's age, fertility desire and the type of present hyperplasia. Progestagens are still the most commonly used medical treatment modality in these patients. Response rates are higher in cases without atypia. In selected cases, hysterectomy may be performed as a definitive treatment modality. In this review article current management of the endometrial hyperplasia is summarized in the light of associated literature.

[Endometrial hyperplastic changes and precancerous conditions: terminology and classification].

The paper presents the data available in the literature on the debated aspects of the terminology and classification of endometrial hyperplastic lesions, precancerous conditions of the corpus uteri. Particular emphasis is laid on the low reproducibility of the histological diagnosis of endometrial changes in accordance with the WHO criteria. Focus is on the disadvantages of a morphometric study for diagnosing endometrial intraepithelial neoplasia. The authors show it expedient to simplify the WHO classification and to adopt the uniform criteria for and terms of endometrial hyperplastic changes and precancerous conditions.

Congruence Between 1994 WHO Classification of Endometrial Hyperplasia and Endometrial Intraepithelial Neoplasia System.

OBJECTIVES: To assess congruence between World Health Organization (WHO) 1994 and endometrial intraepithelial neoplasia (EIN) classification systems of endometrial hyperplasia. METHODS: Systematic review and meta-analysis were performed by searching electronic databases for studies that classified endometrial hyperplasia according to both WHO 1994 and EIN systems. Congruence was based on the rate of specimens classified as EIN in WHO categories, which should be virtually 0.000 in nonatypical hyperplasia (NAH) and 1.000 in atypical hyperplasia (AH). Subgroup analyses were performed based on architecture complexity. RESULTS: Eight studies with 1,352 hyperplasias were included. Congruence with EIN criteria was fair in NAH (0.241) and moderate in AH (0.815). Subgroup analyses of NAH showed high congruence in simple NAH (0.065), null in complex NAH (0.517), null in simple AH (0.148), and high in complex AH (0.901). CONCLUSIONS: WHO 1994 system is not congruent with the EIN system and cannot be directly translated into a dual classification.

Complexity of glandular architecture should be reconsidered in the classification and management of endometrial hyperplasia.

The 2014 World Health Organization (WHO) classification of endometrial hyperplasia (EH) defines premalignant EH based on only cytologic atypia, disregarding architecture complexity. We aimed to assess the impact of architecture complexity on the risk of cancer in non-atypical EH. A systematic review and meta-analysis was performed by searching electronic databases form their inception to October 2018. All studies assessing the rates of progression to cancer in non-atypical EH (simple vs complex) were included. Pooled relative risk (RR) for cancer progression was calculated; a p-value < 0.05 was considered significant. Eight studies with 1066 women were included. The risk for progression of non-atypical EH to cancer was significantly higher in complex EH than in simple EH (p < 0.0001), with an RR of 4.90. In conclusion, the complexity of glandular architecture significantly increases the risk of cancer in non-atypical EH. Complex non-atypical EH may be regarded as a low-risk premalignant lesion rather than a benign condition.

The endometrial hyperplasias revisited.

The proliferating lesions in the endometrium form a morphological continuum extending from benign to malignant, through a transitional pre-invasive stage. Within this spectrum, several classifications of endometrial hyperplasia have been developed over the years in which the precancerous lesions gained a substantial distinction, although not without inconsistencies in definitions and terminology. The revised WHO 1994 classification explicitly recognizes cytological atypia as the defining feature for distinguishing genuine hyperplastic lesions (simple and complex endometrial hyperplasia) from those that are potentially precancerous (simple and complex atypical endometrial hyperplasia) and puts an end to the verbal anarchy by adopting a common language of communication. This taxonomy, however, was criticized for complexity and low level of reproducibility. Thus, in the name of improved reproducibility a new classification was recently proposed which (a) combines simple and complex endometrial hyperplasia within one diagnostic category known as endometrial hyperplasia and (b) defines new criteria for recognising the precancerous lesions: a monoclonal growth, known as endometrial intraepithelial neoplasia (EIN), comprising clusters of crowded glands, greater than 1 mm in diameter, having a cytologically altered epithelium. The EIN concept was challenged of not being independently tested and received with great enthusiasm by some scholars and relative skepticism by others.

Uterine adenomyosis: a need for uniform terminology and consensus classification.

Modern imaging techniques allow non-invasive diagnosis of adenomyosis, a relatively common disorder characterized by the presence of heterotopic endometrial glands and stroma in the myometrium with hyperplasia of the adjacent smooth muscle. The study of adenomyosis is greatly hampered by a lack of clear terminology and the absence of a consensus classification of the lesions. Any classification of adenomyosis must begin with an evaluation of the myometrium underlying the endometrium, the so-called junctional zone, since homogeneous thickening of this zone has become the standard criterion for non-invasive diagnosis. Although transvaginal sonography is useful for the detection of adenomyosis, the technique is highly operator dependent. Magnetic resonance imaging provides superior soft tissue resolution and currently represents the most accurate technique for non-invasive diagnosis. Adenomyosis represents a spectrum of lesions, ranging from increased thickness of the junctional zone to overt adenomyosis and adenomyomas, which in turn can be subclassified. It is increasingly recognized that adenomyosis is often associated with pelvic endometriosis yet the contribution of myometrial lesions to clinical symptoms, such as infertility and pain, remains poorly understood. Moreover, recent studies indicate that adenomyosis is a progressive disease that changes in appearance during the reproductive years. A consensus classification of uterine adenomyosis is urgently required.