Atypical umbilical endometriosis: Microscopic and immunohistochemical characterization / Endometriosis atípica umbilical. Caracterización microscópica e inmunohistoquímica

Introduction: Atypical endometriosis is considered a precursor lesion to cancer associated with endometriosis. Two types of atypical endometriosis have been proposed: an architectural type with a higher risk of malignancy and a cytological type with a lower potential for malignancy. Main symptoms and/or clinical findings: A 37-year-old Caucasian woman presented with umbilical bleeding coinciding with menstruation. On physical examination, two small, bluish lesions were observed in the umbilical scar. Primary diagnosis: This clinical case is of interest because it describes a lesion of atypical architectural endometriosis located in the navel. Therapeutic interventions and results: The microscopic and immunohistochemical characteristics of the lesion were examined. The presence of nuclear stratification, hyperchromatism, and pleomorphism were observed as microscopic qualities. In terms of the immunohistochemical panel, the degree of cell proliferation was analyzed using Ki 67, BAF250a was used as the surrogate marker of ARID 1A, inflammation was assessed through COX, and estrogen and progesterone receptors were examined. The results showed increased cellular activity, the presence of inflammation, and no mutation of the ARID1a gene, with moderate cell proliferation. Conclusion: Umbilical endometriosis is rare, and while malignancy is infrequent, it is possible. For this reason, a complete anatomopathological study including an immunohistochemical panel should be performed to diagnose atypical endometriosis.(AU)

Introducción: La endometriosis atípica está considerada como una lesión precursora de cáncer asociado a endometriosis. Se han propuesto 2 tipos de endometriosis atípica, una arquitectural con mayor riesgo de malignización y otra citológica cuyo potencial de malignización es menor. Principales síntomas y/o hallazgos clínicos: Una mujer de 37 años caucásica consulta por sangrado catamenial umbilical. A la exploración física se observan 2 pequeñas lesiones umbilicales azuladas. Diagnóstico principal: Este caso clínico es interesante porque se describe una lesión de endometriosis atípica arquitectural localizada en el ombligo. Intervenciones terapéuticas y resultados: Se ha descrito sus características microscópicas e inmunohistoquímicas para caracterizarla. La presencia de estratificación nuclear, hipercromatismo y pleomorfismo como cualidades microscópicas y en cuanto al panel inmunohistoquímico se ha analizado el grado de proliferación celular mediante el Ki-67, BAF250a como el marcador subrogado del ARID1A, el grado de inflamación mediante COX y los receptores estrogénicos y gestagénicos. Los resultados demuestran que tiene una actividad celular aumentada, presencia de inflamación y no mutación del gen ARID1A con moderación proliferación celular. Conclusión: La endometriosis umbilical es poco frecuente y su malignización, aunque rara es posible. Por esta razón, se debería realizar un estudio anatomopatológico completo que incluya un panel inmunohistoquímico en aras de diagnosticar endometriosis atípica.(AU)

Evaluación clínica y manejo de la endometriosis: resumen de la orientación técnica MINSAL para el manejo de personas con endometriosis / Clinical evaluation and management of endometriosis: summary of the national ministry of health guidance for the management of people with endometriosis

La endometriosis es una de las enfermedades más comunes en las edades reproductivas y afecta la calidad de vida y la fertilidad de las pacientes. A la fecha, no existen guías clínicas nacionales disponibles para la evaluación y el manejo de esta patología. El presente corresponde a una síntesis del trabajo liderado por la Sociedad Chilena de Obstetricia y Ginecología y el Ministerio de Salud para la conformación de una Orientación Técnica que sirva a los profesionales de salud para el mejor manejo de las personas con esta dolencia. Esta revisión presenta pautas para el diagnóstico y el manejo de la endometriosis en el ciclo de vida de la persona, incluyendo la adolescencia y la menopausia, y en personas infértiles. De igual manera, da directrices para el manejo médico, terapias complementarias y tratamiento quirúrgico, junto con el seguimiento en el tiempo y la estructuración en red del manejo de las personas con endometriosis.

Endometriosis is one of the most common diseases in reproductive ages and affects the quality of life and fertility of patients. To date, there are no national clinical guidelines available for the evaluation and management of this pathology. This paper corresponds to a synthesis of af effort led by the Chilean Society of Obstetrics and Gynecology and the Ministry of Health to create a national Guideline that serves health professionals for the better management of people with this condition This review presents recommendations for the diagnosis and management of endometriosis in the life cycle of the person with endometriosis including adolescence, menopause and in infertile persons. Moreover, provides guidelines for medical management, complementary therapies and surgical management, along with monitoring over time and network structuring of the management of people with this disease.

Are we better off using multiple endometriosis classifications in imaging and surgery than settle for one universal less than perfect protocol? Review of staging systems in ultrasound, magnetic resonance and surgery.

There are multiple classifications in imaging and surgery of endometriosis and in this article, we offer a review of the main evaluation systems. The International Deep Endometriosis Analysis group consensus is the leading document for ultrasound assessment, while magnetic resonance imaging is guided by the European Society for Urogenital Radiology recommendations on technical protocol. In surgery, the revised American Society for Reproductive Medicine classification is the oldest system, ideally combined with newer classifications, such as Enzian or Endometriosis Fertility Index. Recently, The World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project introduced detailed proforma for clinical and intraoperative findings. There is still no universal consensus, so the initial emphasis should be on the uniform reporting of the disease extent until research clarifies more the correlations between extent, symptoms and progression in order to develop a reliable staging system.Impact StatementWhat is already known on this subject? There have been several reviews of surgical classifications, comparing their scope and practical use, while in the imaging the attempts for literature review has been scarce.What do the results of this study add? This is the first up to date review offering detailed analysis of the main classification systems across the three main areas involved in endometriosis care - ultrasound, MRI and surgery. The mutual awareness of the radiological classifications for surgeons and vice versa is crucial in an efficient multidisciplinary communication and patient care. On these comparisons we were able to demonstrate the lack of consensus in description of the extent of the disease and even further lack of prognostic features (with the exemption of one surgical system).What are the implications of these findings for clinical practice and/or further research? Future attempts of scientific societies should focus on defining uniform nomenclature for extent description. In the second step the staging classification should encompass prognostic value (risk of disease and symptoms recurrence).

Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature).

Endometriosis is a "mysterious" disease and its exact cause has not yet been established. Among the etiological factors, congenital, environmental, epigenetic, autoimmune and allergic factors are listed. It is believed that the primary mechanism of the formation of endometriosis foci is retrograde menstruation, i.e., the passage of menstrual blood through the fallopian tubes into the peritoneal cavity and implantation of exfoliated endometrial cells. However, since this mechanism is also observed in healthy women, other factors must also be involved in the formation of endometriosis foci. Endometriosis is in many women the cause of infertility, chronic pain and the deterioration of the quality of life. It also represents a significant financial burden on health systems. The article presents a review of the literature on endometriosis-a disease affecting women throughout the world.

Mapping of endometriosis in patients with unilateral endometrioma.

ABSTRACT: To map the distribution of the sites most affected by endometriosis in patients with unilateral ovarian endometriomas.A descriptive case series of 84 patients with unilateral endometriomas undergoing laparoscopy for the treatment of endometriosis. To evaluate the distribution of the sites of endometriosis lesions, the peritoneal compartments were divided into 5 zones: zone 1/the anterior compartment, including the anterior uterine serosa, vesicouterine fold, round ligament, and bladder; zone 2/the lateral compartment, including the left and right ovary, ovarian fossa, tubes, mesosalpinx, uterosacral ligaments, parametrium, and the ureter; zone 3/the posterior compartment, including posterior uterine serosa, the pouch of Douglas, posterior vaginal fornix, and bowel; zone 4 consisting of the abdominal wall; and zone 5 consisting of the diaphragm.Of the 5 zones evaluated, the lateral compartment (zone 2) was the most affected, with 60.7% of the patients having dense adhesions around the left ovarian fossa and 57.1% around the right ovarian fossa. The ovarian endometriomas were more commonly found on the left side (54.8%) compared to the right (45.2%). In the posterior compartment (zone 3), the posterior cul-de-sac was obliterated in 51.2% of the patients. In the anterior compartment (zone 1), there were lesions in the vesicouterine fold in 30.9% of the patients and in the bladder in 19%. Lesions were found in the abdominal wall (zone 4) and diaphragm (zone 5) in 21.4% and 10.7% of patients, respectively.Unilateral endometriomas are important markers of the severity of endometriosis.

The #Enzian classification: A comprehensive non-invasive and surgical description system for endometriosis.

Advances in preoperative diagnostics as well as in surgical techniques for the treatment of endometriosis, especially for deep endometriosis, call for a classification system, that includes all aspects of the disease such as peritoneal endometriosis, ovarian endometriosis, deep endometriosis, and secondary adhesions. The widely accepted revised American Society for Reproductive Medicine classification (rASRM) has certain limitations because of its incomplete description of deep endometriosis. In contrast, the Enzian classification, which has been implemented in the last decade, has proved to be the most suitable tool for staging deep endometriosis, but does not include peritoneal or ovarian disease or adhesions. To overcome these limitations, a comprehensive classification system for complete mapping of endometriosis, including anatomical location, size of the lesions, adhesions and degree of involvement of the adjacent organs, that can be used with both diagnostic and surgical methods, has been created through a consensus process and will be described in detail-the #Enzian classification.

Structured manual for MRI assessment of deep infiltrating endometriosis using the ENZIAN classification.

PURPOSE: Proposal of a systematic approach to assess Deep infiltrating endometriosis (DIE) through pelvic Magnetic resonance imaging (MRI) using the Enzian classification and examination of inter-rater agreement. METHODS: Three radiologists reviewed 23 MRI of patients with pelvic DIE at one tertiary referral center retrospectively and independently. Inclusion criteria were intraoperative confirmation of DIE and MR imaging according to ESUR (European Society of Urogenital Radiology) guidelines. Assessment of the anatomical pelvic compartments was performed using a manual based on the Enzian classification with step-by-step instructions using recommended planes and sequences presented here. Interrater agreement was measured using kappa statistics. RESULTS: According to the intraoperative site lesions in 53 anatomical compartments were present. Interrater agreement was best for compartments A (0.255) and FB (0.642). For FI (0.204) and B (0.146) it was slight, there was poor agreement for C (- 0.263), FA (- 0.022), and FO (- 0.030), respectively, and as for FU, no ureter infiltration was described. CONCLUSION: MRI as a noninvasive diagnostic tool offers essential advantages regarding classification and therapy planning for patients with DIE. However, its assessment is difficult and a more systematic approach is needed. Our proposed manual based on the Enzian classification is reproducible and could support radiologists and gynecologists.

Transvaginal Sonographic Imaging and Associated Techniques for Diagnosis of Ovarian, Deep Endometriosis, and Adenomyosis: A Comprehensive Review.

Imaging of endometriosis and in particular deep endometriosis (DE) is crucial in the clinical management of women facing this debilitating condition. Transvaginal sonography (TVS) is the first-line imaging method and magnetic resonance imaging (MRI) may provide supplemental information. However, the delay in diagnosis of up to 10 years and more is of concern. This problem might be overcome by simple steps using imaging with emphasis on TVS and referral to tertiary care. Finally, TVS is crucial in mapping extent and location of disease in planning surgical therapy and counseling women regarding various therapeutic options. This review presents the available data on imaging of endometriosis with a focus on TVS and MRI for DE, adenomyosis, and ovarian endometriomas including endometriomas in pregnancy as well as the use of "soft markers." The review presents an approach that is in accordance with the International Deep Endometriosis Analysis (IDEA) group consensus statement.

The follicular fluid metabolome differs according to the endometriosis phenotype.

RESEARCH QUESTION: Is there a follicular fluid-specific metabolic profile in deep infiltrating endometriosis (DIE) depending on the presence of an associated ovarian endometrioma (OMA) that could lead to the identification of biomarkers for diagnosis and prognosis of the disease? DESIGN: In this prospective cohort study, proton nuclear magnetic resonance (1H-NMR) experiments were carried out on 50 follicular fluid samples from patients presenting with DIE, associated or not associated with an OMA, and 29 follicular fluid samples from patients with infertility caused by a tubal obstruction. RESULTS: Concentrations of glucose, citrate, creatine and amino acids such as tyrosine and alanine were lower in women with DIE than control participants, whereas concentrations of lactate, pyruvate, lipids and ketone bodies were higher. Metabolic analysis revealed enhanced concentrations of glycerol and ketone bodies in patients with OMA, indicative of an activation of lipolysis followed by beta-oxidation. Concentrations of lactate and pyruvate were increased in patients without OMA, whereas the concentration of glucose was decreased, highlighting activation of the anaerobic glycolysis pathway. Differences in concentrations of amino acids such as threonine and glutamine were also statistically relevant in discriminating between the presence or absence of OMA. CONCLUSIONS: Results indicate a mitochondrial dysregulation in endometriosis phenotypes, with a modified balance between anaerobic glycolysis and beta-oxidation in OMA phenotypes that could affect the fertility of women with endometriosis. As the composition of the follicular fluid has been shown to be correlated with oocyte development and outcome of implantation after fertilization, these findings may help explain the high level of infertility in these patients.

Classification algorithm of patients with endometriosis: Proposal for tailored management.

Endometriosis is a pseudoneoplastic disease that has a significant personal and social impact. Unlike other neoplastic diseases, its management is burdened by uncertainty and controversy. The aim of this article is to furnish clinicians with a simple, useful and updated tool to select an appropriate diagnostic-therapeutic care pathway for affected women. Guidelines and recommendations cite advances in diagnostics, novel medications and optimized assisted reproductive techniques; however, such advancements have not simplified the management of endometriosis, since they often lack an integrated, multidisciplinary view of diagnostic, therapeutic and reproductive scenarios that inevitably overlap in the management of the disease. We selected and compared major society guidelines on the diagnosis and treatment of endometriosis. Three international and 5 national guidelines were analyzed. The overlapping recommendations were extracted and mapped, developing a simplified diagnostic-therapeutic care pathway in the form of an algorithm. We subdivided the patient population attending our tertiary referral center according to 4 decision nodes: type (deep infiltrating endometriosis or isolated endometrioma); stage (I-IV according to the revised American Society for Reproductive Medicine classification); predominant health problem (pain or infertility); and fertility potential of the couple (normal/abnormal screening fertility). We identified 9 classes, each corresponding to a suggested mode of treatment (medical, surgical or assisted reproductive technique) according to the most recent evidence published. This simplified scheme is designed to standardize treatment and is intended for use as a tool in diagnostic and therapeutic planning with a view to reduce inappropriate treatment.

Exploring the challenges for a new classification of adenomyosis.

The availability of non-invasive diagnostic tests is an important factor in the renewed interest in adenomyosis, as the disease can now be more accurately mapped in the uterus without a need for hysterectomy. An agreed system for classifying and reporting the condition will enhance our understanding of the disease and is envisaged to enable comparison of research studies and treatment outcomes. In this review, we assess previous and more recent attempts at producing a taxonomy, especially in view of the latest proposal for subdivision of adenomyosis into an internal and an external variant. In this context, we also explore the uncertainties linked to classifying involvement of the uterovesical pouch, the pouch of Douglas and lesions in the outer myometrium. Two opposing hypotheses are forwarded to explain the pathogenesis of these variants, namely that disease localized in these areas originates from an invasion by uterine adenomyosis of peritoneal organs; alternatively, that lesions present in the outer myometrium originate from peritoneal endometriosis. At the root of debates around these opposing theories of pathogenesis is fragmentary evidence. Because of the limitations of currently available evidence, and until this issue is resolved, broad agreement on a hypothesis to underpin any proposed classification is unlikely.

Magnetic resonance imaging versus transvaginal ultrasound for complete survey of the pelvic compartments among patients with deep infiltrating endometriosis.

OBJECTIVE: To compare the performance of magnetic resonance imaging (MRI) and transvaginal ultrasound (TVU) in detecting deep infiltrating endometriosis (DIE), using Enzian classification. Secondarily, to evaluate the influence of nodule size on the accuracy of MRI and TVU. METHODS: A retrospective study was carried out at "La Paz" University Hospital, Madrid, Spain, between April 2012 and December 2014. Inclusion criteria were suspicion of DIE at gynecologic examination, indication to undergo TVU, MRI and surgery. Exclusion criteria were previous hysterectomy, bowel resection, or urinary tract surgery. The diagnosis of DIE using MRI or TVU was considered positive when it correlated with histology. Sensitivity, specificity, accuracy, and mean size of the nodule were calculated. RESULTS: In the present study involving 48 women, TVU demonstrated greater accuracy than MRI for recto-vaginal (77% vs 69%) and vaginal (94% vs 89%) endometriosis. MRI showed greater accuracy (96%) than TVU (92%) for bladder endometriosis. The size of the nodule did not have a significantly different effect on the accuracy of TVU compared with MRI. CONCLUSION: In the present study, TVU provided a more accurate localization of vaginal and recto-vaginal endometriosis as compared with MRI; however, MRI should be recommended if a suspicion of bladder endometriosis exists. The nodule size did not seem to influence the accuracy of the two techniques.

Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment.

Endometriosis is an enigmatic disease that could start at birth. Its pathogenesis is supported by different theories. Accumulating facts relate it to a multigenic disorder. In this review of recent publications, the principal symptoms of the disease, pain and infertility, as well as its pathogenesis, diagnosis, and classification will be addressed. Endometriosis presents three main variants: superficial peritoneal disease, deep infiltrating endometriosis, and ovarian endometriomas. The management of the disease, surgery, and medical and alternative therapies will be discussed. Special reference will be made to the quality of surgery and how to understand patients with endometriosis and endometriosis.

[Endometriosis: Assessment of the Ultrasound-Based Endometriosis Staging System score (UBESS) in predicting surgical difficulty]. / Endométriose : évaluation du score Ultrasound-Based Endometriosis Staging System (UBESS) dans la prédiction de la difficulté chirurgicale.

OBJECTIVES: Surgical management of endometriosis may require different levels of surgical skill which influences the orientation of the patient. The Ultrasound-Based Endometriosis Staging System (UBESS) is a score developed in 2016 to predict the difficulty of surgery. To study the correlation between UBESS score and two main surgical classifications in the literature. METHODS: Study performed at the center of Poissy, France, between July 2016 and December 2017. Patients who underwent prospective UBESS staging then operated of their endometriosis were included. The patients were classified according to the levels of surgical difficulty of the Royal College of Obstetricians and Gynecologists (RCOG) and the classification created by Chi et al. The criterion of judgment was the correlation between the UBESS stages and RCOG and CHI levels. In a second analysis, we determined the predictive value of the operative plan for items included in the systematic sonographic evaluation described by Menakaya et al. RESULTS: Thirty-three patients were included in the study. Correlation was found to be low between UBESS and RCOG (θ=0.22) and between UBESS and CHI (θ=0.30). The prediction of the operative plan was good for endometrioma, sites specific tenderness, sliding sign, vaginal and digestive tract involvement; but modest for the anterior compartment and uterosacrals ligaments. CONCLUSION: In our study on a small number of patients, the UBESS score does not adequately predict the surgical difficulty. Taken separately, the items of systematic sonographic evaluation based on 5 domains successfully predict the operative plan.

Endometriosis and infertility: Insights into the causal link and management strategies.

When evaluating the correlation between endometriosis and infertility with application of the evidence-based guidelines to establish causality in medicine, it becomes apparent that endometriosis causes infertility. This is supported by a strong and consistent association between the two in various settings (prevalence, natural conception, intrauterine insemination (IUI), and assisted reproductive technologies (ARTs)), evidence for a temporal relation, arguments for a dose-response gradient, and proven effects of the removal of lesions on infertility. Next to surgical treatment of endometriosis lesions, medically assisted reproduction treatments such as IUI and ART such as in vitro fertilization are cornerstones of the management of endometriosis-related infertility. Because the revised American Society for Reproductive Medicine (rASRM) staging system is poorly correlated with pregnancy rates as opposed to the Endometriosis Fertility Index (EFI), the latter should be used as the preferred clinical tool to counsel patients on their postoperative fertility management options.

Endometriosis classification according to pain symptoms: can the ASRM classification be improved?

Endometriosis is a chronic disease that affects 5-15% of women of the reproductive age. Different classifications systems have been proposed to categorize endometriosis. In 1979, the American Fertility Society proposed a new system for the classification of endometriosis to correlate surgical findings of endometriosis with fertility, and this system was revised in 1996 (rASRM). Despite the fact that the rASRM classification system is widely used and accepted worldwide, it has limitations. The objectives of this study were to critically assess and discuss the current classification of endometriosis according to pain.