Accessory cavitated uterine malformation (ACUM): A scoping review

Study conception by Stefan Timmerman and Wouter Froyman. Lauren Stubbe and Stefan Timmerman did study screening, data extraction and data analysis. Writing, subsequent critical revision and final approval by all authors.

We identified a total of 3645 records, of which 53 articles were included (the PRISMA flow chart is presented in Figure  2 ). We identified 144 potential cases of which 115 cases provided sufficient information to be classified and were in accordance with one or more of the most commonly used definitions of ACUM. We did not find any articles in the gray literature. The studies included and their characteristics are summarized in Supporting Information (Appendix  S2 ). All papers were case reports or case series, ranging from 1 to 20 cases (median 1). Preferred Reporting Items for Systematic Reviews and Meta‐Analysis flow chart. Out of the 115 cases of probable ACUM, the term ACUM was most commonly used (68/115, 59.1%). followed by JCA (35/115, 30.4%). Less common terms were cystic adenomyosis (7/115, 6.1%), uterus‐like mass (3/115, 2.6%), adenomyotic cyst (1/115, 0.9%), and adenomyoma (1/115, 0.9%). The definitions for ACUM as described by Acién et al. and for JCA by Takeuchi et al. were the most predominantly used. The nine included cases described as “cystic adenomyoma”, “adenomyotic cyst” and “adenomyoma” resembled ACUM, based on the typical localization and characteristics. Moreover, “uterus‐like mass” as described by Cozzutto et al., was used in three cases for uterine lesions. 15 Since the mentioned cases had the typical localization and histopathological findings, we considered these cases to be ACUM. The median age at diagnosis of the 115 included cases was 21.5 years, with a range of 13 to 48 years. The most frequently reported complaints were dysmenorrhea (88/115, 76.5%) and noncyclic pelvic pain (65/115, 56.5%). Dyspareunia (5/115, 4.3%) and abnormal uterine bleeding (2/115, 1.7%) were less common. The average duration of the symptoms before diagnosis was 24 months (range: 3–288 months). A total of 25/53 (47%) studies reported on both age at menarche and time of symptom onset, which was 13 years (10–17) and 17 years (12–37), respectively. There was a median interval of 3 years (0–13) between menarche and onset of symptoms. The description of the ultrasound examination was provided in total for 69/115 (60%) of cases (Table  2 ). Ground‐glass echogenicity with a smooth inner lining was the most frequently reported appearance (Figure  3 ). Naftalin et al. described the vascularity of ACUM as Doppler flow seen in the outer rim, not markedly different from that of the surrounding myometrium. 4 Aside from this report Doppler flow was rarely and inconsistently reported, precluding any further conclusions. Characteristics of accessory cavitated uterine malformation (ACUM) on imaging. Abbreviation: MRI, magnetic resonance imaging. Hemorrhagic ( n  = 4), mixed ( n  = 4), blood ( n  = 2), hematometra ( n  = 1). Ultrasonographic images of ACUM (white arrows). Left: Transvaginal ultrasound which shows the ACUM as an anechoic lesion, lateral in the uterine corpus. The uterine cavity is marked by a white star. Right: Transvaginal ultrasound with the uterus visualized in the transverse plane. The ACUM is visualized as cystic lesion with ground glass echogenicity. The uterine cavity is marked by a white star. MRI descriptions were provided for 70/115 (61%) of cases and a variety of features were reported. Blood appears with high signal intensity in both T2 and T1 weighted (T1W) sequences, which was present in 43/46 (95.5%) of cases that reported the T1W images. Table  3 provides an overview of the reported measurements and location of the ACUM. Age and largest lesion diameter were both present in 109 cases. For these, we observed a moderate positive correlation (Spearman's correlation: 0.55). Characteristics of the accessory cavitated uterine malformation (ACUM) based on Imaging (ultrasound or magnetic resonance imaging). The presence of a normal uterine cavity with bilateral ostia was confirmed by additional hysteroscopy or hysterosalpingography in 38/115 (33%) cases (Figure  4 ). Accessory cavitated uterine malformation (ACUM) (white arrow) visualized during laparoscopy. We identified 29/115 (25%) cases with associated gynecological abnormalities. These were endometriosis ( n  = 9), adenomyosis ( n  = 6), uterine fibroids ( n  = 3), polycystic ovarian morphology ( n  = 2), ovarian cysts ( n  = 5), an ectopic pregnancy ( n  = 1), a minor congenital abnormality of the urogenital tract not further specified ( n  = 1), an accessory fallopian tube ( n  = 1) and a contralateral hydrosalpinx ( n  = 1). All but one case who was lost to follow‐up reported on treatment of the ACUM. In 95/114 (83%) cases, surgical removal was described. Nonsurgical options have been explored in the most recent articles. An overview of reported treatments is demonstrated in Table  4 . In only 45 cases the absence of adverse events was explicitly noted, while no adverse events were reported across the various management strategies for the remaining. Follow‐up was reported for 57 cases and varied between 3 and 74 months. Surgical and conservative treatment of accessory cavitated uterine malformation (ACUM). During pregnancy. One case was lost to follow‐up after diagnosis. Abbreviations: TAH, total abdominal hysterectomy; TLH, total laparoscopic hysterectomy. The predominantly used surgical technique was laparoscopic excision. Of the 99 cases who finally underwent surgery, 19/99 (19.2%) cases lacked any information on postoperative symptoms. For the remaining cases, 64/80 (80%) reported complete resolution of symptoms and 16/80 (20%) partial resolution of dysmenorrhea or pelvic pain. Nonsurgical treatment was attempted in 75/114 (65.8%) cases (Table  4 ). In 15/75 (20%) cases, multiple conservative treatments were attempted. It is important to note that of these, 56/75 (74.7%) had initially no formal diagnosis of ACUM (recognizing the presence of a lesion based on medical investigations) when treatment was initiated. Interventional treatment options included sclerotherapy (alcoholic n  = 7, lauromacrogol n  = 1), and ultrasound‐guided drainage ( n  = 1). Expectant management was attempted in three cases, and medical treatment in 70. Medical treatment consisted of combined estrogen/progesterone oral contraceptives (34/70, 48.5%), nonsteroidal anti‐inflammatory drugs (NSAID) (24/70, 34.3%), the progesterone‐only pill (11/70, 15.7%), nonspecified analgesics (9/70, 13%), gonadotrophin‐releasing hormone agonists (8/70, 7%), the levonorgestrel‐releasing intrauterine device (LNG‐IUD) (6/70, 5.2%), nonspecified medical treatment (4/70, 5.7%) and aromatase inhibitor (1/70, 1.4%). In 60/70 (85.7%) of the cases initially treated with medical or hormonal treatment, the complaints were persistent. In 4/8 (50%) cases that received interventional treatment, this was attempted a second time (US‐guided drainage, n  = 1 and ethanol sclerotherapy, n  = 3), then after a formal diagnosis of ACUM. A total of 56 cases reported that medical treatment was attempted empirically without a formal diagnosis of ACUM. When no symptom improvement was obtained, further investigations were performed, an ACUM diagnosed and surgical excision performed secondarily. This sequence of events was described in 56/95 (59%) of the surgically managed cases (Table  4 ). In 19/114 (16.7%) cases, nonsurgical treatment was initiated after a formal diagnosis of ACUM, of which four (21%) required subsequent surgical treatment. Seven of these cases (one providing medical treatment and 6 sclerotherapy) report a follow‐up, with a median of 18 months (range 12–24) and no recurrence of symptoms. In one case, there was reported partial regression under combined oral contraceptive treatment. 9 Of the six cases with sclerotherapy, five cases had partial regression and one full regression during the follow‐up period. 4 , 16 , 17 , 18 Out of the 99 cases that underwent surgical management, a large proportion of articles did not specify which histopathological findings were made to support the diagnosis. Others described a cavity lined with normal endometrial tissue surrounded by myometrium as the typical finding. 2 In total, 18/115 (15.7%) women were parous before the diagnosis of ACUM; 18 cases described previous primary or secondary sub‐ or infertility. Three women were pregnant at the time of diagnosis. In seven cases, of which five were surgically managed and two with sclerotherapy, eight pregnancies were reported. All resulted in live births and no adverse pregnancy outcomes were reported. The mode of delivery was cesarean section in one, 3 vaginal delivery in two, 3 and not specified in five. 16 , 17 , 19 , 20 , 21 In 74 cases, the patient was reported not to be pregnant at time of publication, although follow‐up and a fertility wish after treatment were rarely explicitly reported. In 30 cases no information on pregnancy or not after treatment was provided.

In this scoping review, we identified 53 articles that reported on 115 cases likely representing ACUM. Most studies were case reports, the largest case series consisted of 20 women. 4 Reporting of baseline characteristics, diagnostic findings, rationale for treatment decision, and symptoms was inconsistent. Several knowledge gaps have been identified in our study. First, there was a lack of standardized treatment strategies (both conservative and surgical) and long‐term (patient‐reported) follow‐up data. Second, there was insufficient information available on the fertility wish and subsequent fertility treatments of patients with ACUM following the initial management. Finally, there was little information on pregnancy outcomes, which makes it challenging to ascertain the impact of the condition and its management on maternal and fetal health, despite a few cases demonstrating a reassuring course. We suggest the term “accessory cavitated uterine malformation” should be used and propose the following definition, slightly modified from Naftalin et al. 4 : “A cavitated lesion surrounded by a myometrial mantle, in continuity with the anterolateral uterine wall and located beneath the insertion of the round ligament and the interstitial portion of the fallopian tubes. To distinguish ACUM from other obstructive abnormalities, a normal uterine cavity should be visualized”. This definition was applicable to 99% of reviewed cases that reported an ACUM in detail. We favor “malformation” over the sporadically used term “mass”, since “mass” could give the impression that ACUM is tumorous, while it is a benign cystic lesion. 4 While the term JCA appears to be a plausible choice, highlighting the presence of ectopic endometrial tissue in the myometrium, it is not ideal for several reasons. First, adenomyosis exhibits a wide variety of morphological and clinical presentations. ACUM, on the contrary, appears in the same localization with very little variation in structural presentation and often without any other signs of associated adenomyosis. Second, the term “juvenile” seems too restrictive since ACUM can also be diagnosed in women older than 30 years old. 4 Other terms used in the literature which have overlap with ACUM are poorly defined, without indicating a precise localization. Examples include “uterus like mass”, “mullerianosis”, and “Mullerian choristoma”, the latter defined as “a developmental tumor‐like growth of microscopically normal tissue in an abnormal location”. 22 During the selection and inclusion of the cases, we encountered benefits and limitations in the definitions proposed by Acién et al., Takeuchi et al., and Naftalin et al. 2 , 3 , 4 Only Acién et al. and Naftalin et al. mention the need for a normal urogenital tract to rule out other congenital Mullerian malformations. Takeuchi et al. did not include this requirement, allowing for instance noncommunicating, rudimentary uterine horns to be classified as ACUM. A limitation of the definition as proposed by Acién et al. is the requirement of excision and histopathologic diagnosis in research settings. As ACUM is a benign lesion and no malignant transformation has been described in the literature so far, conservative management is a valid option. Further limitations of the definition put forward by Takeuchi et al. include the absence of a requirement of a specific localization of the lesion in the uterine contour or near the broad ligament. Thus, extra‐uterine Mullerian choristomas would also fall under this definition. In addition, the requirement of severe dysmenorrhea might lead to diagnostic delay in those cases that have a later onset of dysmenorrhea or present with noncyclic pelvic pain representing an incidental finding of ACUM. Although the definition of Naftalin et al. reflects the imaging and clinical presentation of ACUM most accurately, not all ACUM presented with echogenic content, which is a criterion in their definition. The lesions were predominantly diagnosed in young women with a median age of 21.5 years, but the age range was up to 48 years. All patients diagnosed with ACUM had a history of dysmenorrhea or noncyclic abdominal pain. These symptoms started soon after menarche in most cases and were probably caused by the accumulation of blood in the ACUM, raising the pressure inside the cavity, as seen in other obstructive congenital anomalies. 4 On ultrasound, the cavitated lesions were well‐defined and had a predominantly ground‐glass echogenicity, with a smooth inner lining, corresponding to hemorrhagic cyst content and functional surrounding endometrium, respectively. This was paralleled by findings on MRI, where they appeared with a hyperintense signal in T1W. Differentiating these lesions from other uterine pathologies by ultrasound or MRI is possible due to their typical localization and characteristics. Interestingly, in 24 (21%) cases, the initial diagnosis was a noncommunicating, rudimentary uterine horn. In contrast to the unicorn uterus with a rudimentary horn, 23 ACUM presents with a normal uterine contour and two normal interstitial portions of the fallopian tube. To enhance the visualization of Mullerian anomalies or confirm normal findings, 3D ultrasound plays a crucial role in allowing the coronal display of the uterus. 24 Another differential diagnosis to consider is adenomyotic cysts. However, these do not have a specific localization, tend to be seen in older patients, and are often associated with other adenomyotic changes. 21 Hence, ACUM can be differentiated from inner or middle myometrial adenomyosis and focal adenomyosis of the outer myometrium as described by Chapron et al. or the subtypes of adenomyosis formulated by Kishi et al. 25 , 26 To enable clinicians and imaging specialists to recognize an ACUM and facilitate future prospective research, we recommend a uniform description of different myometrial lesions. We suggest using the terms and definitions published by the morphological uterus sonographic assessment (MUSA) group for describing the sonographic features and measurements of the myometrium and uterine masses. 27 Although there have been a relatively small number of cases, a large variety of management strategies have been reported. In most cases, surgical excision of the ACUM was performed, and for a few cases a cornual excision or a total hysterectomy. Laparoscopic surgery was the most prevalent surgical technique, with only a limited number of cases operated by laparotomy or robotically assisted surgery. Although we noted a large proportion of missing outcome data, these surgical interventions led in most cases to partial or complete remission of the symptoms, without any adverse events. Despite the limited evidence available, laparoscopic excision might be favorable to cornual resection, as this conserves the integrity of the myometrium to a higher degree and thus potentially reduces the risk of uterine rupture in subsequent pregnancies. Recently, ultrasound‐guided sclerotherapy was used in a few cases. 4 The rationale behind this treatment is the destruction of the functional endometrium and thus prevention of the monthly accumulation of menstrual blood. Even though this technique is relatively new in the treatment of ACUM, the effectiveness of alcohol instillation and safety has been shown in the management of ovarian endometriomas. 28 , 29 In addition, the use of lauromacrogol was recently introduced for sclerotherapy of ACUM, which is also claimed to function as a local anesthetic. 16 Lauromacrogol has been used for sclerotherapy of hepatic cysts, and further research is needed to draw conclusions regarding the treatment of ACUM. 30 Ultrasound drainage, followed by cycle suppression to prevent further bleeding can also give symptomatic relief, 31 although this seems a temporary solution since the ectopic endometrium remains functional. However, it is important to note that interventional management was reported in only nine cases, of which three needed repeated treatment. 4 , 16 , 17 , 18 , 31 , 32 Combined oral contraceptives have also been reported; however, mostly initiated as empirical treatment of dysmenorrhea before an ACUM was diagnosed. 33 While this was not shown to be highly effective in the cases of ACUM included in this study, this may be due to a reporting bias. Patients with an undiagnosed ACUM that were successfully treated with combined oral contraceptives are less likely to undergo further diagnostic work‐up and receive a later diagnosis. It is therefore unknown if age at treatment initiation, ACUM size, or other morphological characteristics are associated with successful medical treatment. Research on conservative treatment options remains essential in this field, including longer follow‐up periods and patient‐reported outcomes, both of which were lacking in the included cases. The strengths of this scoping review were a strict and comprehensive methodology and that we identified and included all cases that could possibly represent ACUM, even if published under other terms. This review thus comprised the largest number of published cases on this relatively unknown disease. In contrast to previously published (narrative) reviews, 34 , 35 , 36 we also included both conservatively and surgically managed cases, thus not only considering those with a histological diagnosis. This approach led to the identification of conservative management as a potential treatment option. While consisting of case series, we identified a total of 115 cases and could make a meaningful comparison of the characteristics of each case and summarize the current understanding of ACUM and its synonyms. A limitation of the available data was the incomplete reporting on patient characteristics, diagnostics, treatment, histopathology, and especially follow‐up. Another limitation was that, despite the use of a large range of search terms, we may have missed some cases due to the variety in reporting standards and lexicon used. Also, while we do not believe this affected our results given the overlap with other included terms, “malformation” has only recently been introduced in this context and was not included in our search string. 4 Finally, the cases reported in the literature might present a biased population presenting with symptoms refractory to hormonal treatment and therefore being diagnosed. Asymptomatic cases and patients presenting in units with lower quality of ultrasound scanning and knowledge of ACUM, are likely to be overlooked, and thus not reported.

Unifying previous definitions, we conclude that ACUM is a uterine abnormality, presenting as a cavitated lesion surrounded by a myometrial mantle, in continuity with the anterolateral uterine wall and located beneath the insertion of the round ligament and the interstitial portion of the fallopian tubes. The appearance of ACUM on imaging reflects the surrounding rim of functional endometrium and the hemorrhagic content of the cyst. To distinguish ACUM from other uterine abnormalities, a normal uterine cavity should be visualized. Although it is an increasingly recognized entity, ACUM potentially remains underdiagnosed, given the paucity of reports in the literature and its similarities with other myometrial lesions. Therefore, the use of a unified definition and clear terminology is essential for further research. Furthermore, there is a need for prospective studies that describe standardized management strategies for ACUM and provide long‐term follow‐up data on patient‐reported, fertility and pregnancy outcomes.

Accessory cavitated uterine malformation (ACUM) is a relatively rare uterine malformation, characterized by a noncommunicating, accessory uterine cavity in the absence of other obstructive congenital uterine anomalies (Figure  1 ). 1 Multiple definitions have previously been proposed to describe this entity. 2 , 3 , 4 Drawing illustrating the typical anatomical localization of accessory cavitated uterine malformation (ACUM). Created with Biorender.com . The exact pathogenesis of this rare entity is still unknown. Although most authors believe it is a newly recognized type of Mullerian anomaly or “müllerianosis”, which is developmentally displaced Mullerian tissue, other theories suggest a specific form of metaplasia. 2 , 5 , 6 , 7 ACUMs have been reported under several other terms, like adenomyotic cysts, 8 juvenile cystic adenomyosis (JCA), 3 myometrial cyst, 9 and uterine‐like mass. 10 Currently, ACUM remains unclassified in the uterine anomaly classification of the European Society of Human Reproduction and Embryology (ESHRE), the European Society of Gynecological Endoscopy (ESGE), and the revised American Society of Reproductive Medicine (rASRM). 11 , 12 ACUM is an increasingly recognized but still possibly underdiagnosed clinical entity. The aim of this scoping review was to give a complete overview of reported cases with ACUM. We describe patient characteristics, imaging features, management, and outcomes and in addition identify relevant knowledge gaps, informing future research.

The authors have no conflict of interest to declare.

We systematically searched the databases PubMed, Embase, and Web of Science for possible cases of ACUM, following the guidelines of the PRISMA‐ScR‐checklist for scoping reviews. 13 A gray literature search was performed in ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). Search terms used were “Accessory cavitated uterine mass”, “Adenomyotic cysts”, “cystic myometrial lesion”, “Juvenile cystic adenomyosis”, “Myometrial cyst”, “Mullerianosis”, “non‐communicating uterine horn” and “Uterine‐like Mass”. The complete search strategy can be found in the Supporting Information (Appendix  S1 ). In this article, ACUM and JCA are considered synonyms, and we preferentially use the term ACUM. The final protocol for this scoping review was prospectively registered both in PROSPERO (protocol no. CRD42022329057) and in OSF (Open Science Framework: https://doi.org/10.17605/OSF.IO/GSC98 ). Endnote was used to organize the searches from the different databases. All the database searches were performed on May 27 and 28, 2022, and the gray literature search on May 24. Deduplication was done manually in Endnote. Two independent readers (LS and ST) screened all results of the search, first by title, then again by abstract, and ultimately by full text. Only the studies with consent of both readers were immediately allocated. A third reviewer (WF) was available in case of disagreement. Inclusion criteria were articles that described cystic myometrial lesions, except cystic areas in myomas and sarcomas, published in English, and available full text. No time restrictions were applied, and all types of articles were accepted (i.e., narrative reviews, case reports, systematic reviews, etc.). We did not include articles that did not present any new cases, except when new definitions or terminologies were suggested. To allow an adequate overview and cluster‐related literature, we subdivided the included articles during the title screening into four different categories, based on the terminology used in the original article: “ACUM/JCA”, “cystic adenomyosis”, “mullerianosis”, and “non‐communicating uterine horn”. In all the mentioned categories, we looked for cases that might represent ACUM, as defined by Acién, Naftalin, or Takeuchi (Table  1 ). 2 , 3 , 4 We excluded cases that did not provide enough information to define the case as an ACUM according to any definition. Definitions of accessory cavitated uterine malformation as proposed in the literature. 1) An isolated accessory cavitated mass 2) Normal uterus (endometrial cavity), tubes, and ovaries 3) Surgical case with excised mass and with pathological examination 4) Accessory cavity lined by endometrial epithelium with glands and stroma 5) Chocolate‐brown‐colored fluid content 6) No adenomyosis (if uterus removed), but there could be small foci of adenomyosis in the myometrium adjacent to the accessory cavity 1) Cavitated lesion with a 2) myometrial mantle and 3) echogenic contents in the anterolateral wall of the myometrium beneath the insertion of the round ligament 4) Ruling out obstructive congenital anomalies, such as a communicating and noncommunicating horns, is considered crucial to diagnosis 1) Age 1 cm in diameter, independent of the uterine cavity and covered by hypertrophic myometrium, as seen on radiological images 3) Associated with severe dysmenorrhea If ACUM was suspected based on the full‐text screening, the articles were included and we abstracted a standardized set of variables, which were subdivided into different categories: (1) Terms and definitions used, (2) patient characteristics, (3) diagnosis (findings on magnetic resonance imaging [MRI], ultrasound, hysteroscopy, CT, hysterosalpingography and laparoscopy), (4) treatment, and (5) associated fertility and pregnancy. In case of a missing ultrasound description of the mass, available images were interpreted by a level 2 ultrasound examiner (ST) in gynecological ultrasonography to extract ultrasound variables. 14 Assessing the ultrasound images, we focused on the location, regularity of the inner lining, and the echogenicity of the cystic content. On MRI we collected information on the internal signal on either T1 or T2‐weighted images. No risk of bias appraisal was required since none of the included studies had a comparative design. The extracted standardized set of variables was collected in an online database. A summarizing table is attached in Supporting Information (Appendix  S2 ). Ethical approval was not required due to the nature of the study. Informed consent was obtained for the use of images of patients. Statistical analysis was performed using Google Sheets and Microsoft Excel (version 2305 Build 16.0.16501.20256). Descriptive statistics are reported for all collected variables, using median or mean, depending on sample distribution. To assess a correlation between age and largest lesion diameter, Spearman's correlation was used, given the nonlinear relationship of the variables.

Appendix S1. Appendix S2.