diagnostics Review Differential Diagnosis of Endometriosis by Ultrasound: A Rising Challenge Marco Scioscia 1 , Bruna A. Virgilio 1, Antonio Simone Laganà 2,* , Tommaso Bernardini 1, Nicola Fattizzi 1, Manuela Neri 3,4 and Stefano Guerriero 3,4 1 Department of Obstetrics and Gynecology, Policlinico Hospital, 35031 Abano Terme, PD, Italy; [email protected] (M.S.); [email protected] (B.A.V.); [email protected] (T.B.); [email protected] (N.F.) 2 Department of Obstetrics and Gynecology, “Filippo Del Ponte” Hospital, University of Insubria, 21100 Varese, VA, Italy 3 Obstetrics and Gynecology, University of Cagliari, 09124 Cagliari, CA, Italy; [email protected] (M.N.); [email protected] (S.G.) 4 Department of Obstetrics and Gynecology, Azienda Ospedaliero Universitaria, Policlinico Universitario Duilio Casula, 09045 Monserrato, CA, Italy * Correspondence: [email protected] Received: 6 October 2020; Accepted: 15 October 2020; Published: 20 October 2020 Abstract: Ultrasound is an effective tool to detect and characterize endometriosis lesions. Variances in endometriosis lesions’ appearance and distorted anatomy secondary to adhesions and fibrosis present as major difficulties during the complete sonographic evaluation of pelvic endometriosis. Currently, differential diagnosis of endometriosis to distinguish it from other diseases represents the hardest challenge and affects subsequent treatment. Several gynecological and non-gynecological conditions can mimic deep-infiltrating endometriosis. For example, abdominopelvic endometriosis may present as atypical lesions by ultrasound. Here, we present an overview of benign and malignant diseases that may resemble endometriosis of the internal genitalia, bowels, bladder, ureter, peritoneum, retroperitoneum, as well as less common locations. An accurate diagnosis of endometriosis has significant clinical impact and is important for appropriate treatment. Keywords: endometriosis; adenomyosis; bowel; rectum; ovary; bladder; ureter; abdominal wall; vagina 1. Introduction Endometriosis is a common, chronic, and debilitating gynecological condition that affects between 5–15% of women within their reproductive ages [1,2]. It is characterized by the growth of tissue that mimics endometrial tissue and exhibits the same responses to hormonal changes [1]. However, this abnormal tissue growth occurs outside the uterus, usually on other organs inside the pelvis and abdominal cavity, thus creating endometriosis implants. These endometriosis implants lead to local inflammatory reactions that promote fibrosis and adhesion formation, which create resistance between organs and may result in an altered pelvic anatomy [3]. This cascade of events often causes menstrual and/or chronic pelvic pain, infertility, or malfunction of the affected abdominopelvic organs [1]. In the past decades, ultrasound has become a valuable tool to accompany pelvic bimanual examinations. Currently, both methods are used for the first-line examination and diagnosis of endometriosis [4]. When a patient presents with persistent symptoms of suspected endometriosis, a comprehensive and detailed evaluation of the pelvis by ultrasound is usually prescribed. However, the accuracy of the ultrasound in detecting deep-infiltrating endometriosis depends on the experience Diagnostics 2020, 10, 848; doi:10.3390/diagnostics10100848 www.mdpi.com/journal/diagnostics DiagnosticsDiagnostics2020 2020,,10 10,, 848x FOR PEER REVIEW 22 of 1514 the accuracy of the ultrasound in detecting deep-infiltrating endometriosis depends on the ofexperience the sonographer. of the sonographer. Variances in Variances endometriosis in endo lesionmetriosis appearance lesion and appearan distortedce and anatomy distorted secondary anatomy to adhesionssecondary andto adhesions fibrosis present and fibrosis as major present difficulties as major during difficulties the complete during sonographicthe complete evaluation sonographic of pelvicevaluation endometriosis of pelvic endometriosis [5]. [5]. Therefore,Therefore, aa trained trained ultrasound ultrasound operator operator is neededis needed to detectto detect most most of the of endometriosisthe endometriosis lesions, lesions, and isand required is required to make to soundmake sound judgments judgments and to planand theto pl appropriatean the appropriate treatment treatment [5,6]. It is also[5,6]. important It is also forimportant expert evaluationsfor expert evaluations to include to a diincludefferential a differential diagnosis diagnosis (DD) of endometriosis (DD) of endometriosis to exclude to all exclude other abdominopelvicall other abdominopelvic diseases. Althoughdiseases. Although misdiagnoses misdiagnoses represent represent a small number a small of number cases with of cases unknown with prevalenceunknown prevalence (Figure1), (Figure the clinical 1), the impact clinical of aimpact DD is of great a DD because is great thebecause appropriate the appropriate treatment treatment largely varieslargely based varies on based the diagnosis. on the diagnosis. FigureFigure 1.1. A pyramidpyramid chart thatthat representsrepresents thethe distributiondistribution ofof ultrasoundultrasound scansscans forfor endometriosisendometriosis accordingaccording toto complexity. complexity. Although Although diff differentialerential diagnosis diagnosis must must be considered be considered in each in exam, each the exam, number the ofnumber cases whereof cases it makeswhere ait dimakesfference a difference is relatively is relatively small, although small, although it is fundamental. it is fundamental. 2.2. What a Comprehensive UltrasoundUltrasound forfor EndometriosisEndometriosis ShouldShould InvestigateInvestigate Traditionally,Traditionally, a a routine routine pelvic pelvic ultrasound ultrasound only only evaluates evaluates uterine uterine and ovarianand ovarian lesions, lesions, which which leads toleads the detectionto the detection of elementary of elementary lesions, lesions, such as such endometriomas as endometriomas [7]. However, [7]. However, the evaluation the evaluation should includeshould include the anterior the anterior and posterior and posterior pelvic compartments pelvic compartments to assess to theassess mobility the mobility of pelvic of organspelvic organs [7–10] and[7–10] to improveand to improve the assessment the assessment of endometriosis, of endometr as suggestediosis, as by suggested the International by the DeepInternational Endometriosis Deep AnalysisEndometriosis (IDEA) Analysis consensus (IDEA) [11]. The consensus use of a systematic[11]. The use ultrasound of a systematic approach ultrasound can enhance approach the detection can ofenhance different the endometriosis detection of different locations endometriosis within the pelvis locations [12– 14within], with the a detectionpelvis [12–14], ratethat with is a similar detection to thatrate ofthat magnetic is similar resonance to that of [15 magnetic,16]. resonance [15,16]. EndometriosisEndometriosis can can extend extend to to organs organs other other than than internal internal genitalia, genitalia, such such as the as bowels, the bowels, bladder bladder [1,16], and[1,16], retroperitoneal and retroperitoneal structures structures (e.g., ureters, (e.g., parametria, ureters, parametria, nerves) [17 ],nerves) which [17], significantly which significantly complicates thecomplicates ultrasound the evaluation ultrasound [18 ].evaluation Although all[18]. these Although locations all appear these similar locations on anappear ultrasound similar (nodular, on an sometimesultrasound flat,(nodular, hypoechoic sometimes lesions flat, with hypoechoic the absence lesions of with colored the Dopplerabsence of spots), colored and Doppler they present spots), specificand they features present according specific features to the organaccording or tissue to the involved. organ or tissue In fact, involved. deep-infiltrating In fact, deep-infiltrating endometriosis (DIE)endometriosis of hollow (DIE) organs of induceshollow organs a retraction induces of marginsa retraction with of a margins subsequent with irregular a subsequent profile irregular of both externalprofile of and both internal external surfaces and internal (i.e., bladder,surfaces bowels,(i.e., bladder, and vagina), bowels, whereasand vagina), DIE whereas of dense DIE organs of dense (i.e., peritonealorgans (i.e., and peritoneal retroperitoneal and retroperitoneal organs) maintains organs) a nodular maintains hypoechoic a nodular structure hypoechoic [11]. Less structure frequently, [11]. someLess frequently, lesions may some display lesions vascularity may display with smallvascularity cysts (i.e., with bladder; small cysts Figure (i.e.,2). blad Cysticder; endometriosis Figure 2). Cystic of retroperitonealendometriosis of organs retroperitoneal is a rare event organs that is mainly a rare ev occursent that in patientsmainly occurs with a in history patients of pelvicwith a surgery history (Figureof pelvic3). surgery (Figure 3). Diagnostics 2020, 10, 848 3 of 15 Diagnostics 2020, 10, x FOR PEER REVIEW 3 of 14 Diagnostics 2020, 10, x FOR PEER REVIEW 3 of 14 Figure 2. Bifocal endometriosis of the bladder (arrow). The two lesions present different Figure 2. Bifocal endometriosis of the bladder (arrow). The two lesions present different characteristics Figurecharacteristics 2. Bifocal as the endometriosis one on the right-hand of the sidebladder pres ents(arrow). a typical The solid two aspect lesions while present the left different one is a as the one on the right-hand