Adenomyosis in a uterine horn of a patient with Mayer-Rokitansky-Kuster-Hauser syndrome

A 37-year-old woman with a previous diagnosis of Mayer-Rokitansky-Kuster-Hauser syndrome at 18 years of age was referred from a primary healthcare physician to a gynaecology appointment in our centre. She presented with a 2-year worsening pelvic pain and dyspareunia, symptoms that were previously absent and, at the time, with inadequate relief with oral analgesia. Physical examination showed absent uterine cervix and hypoplastic superior vagina. Transvaginal ultrasound and MRI suggested the presence of an hypoplasic uterus in left rotation. Laparoscopically, two asymmetric rudimentary horns were found, united by a fibrous central band, with an enlarged and congestive left horn. The three structures were removed as a whole. Histopathological examination reported the presence of multiple adenomyotic foci along the full thickness of the left rudimentary horn. The patient had an uneventful postoperative recovery and full remission of her symptoms.

obstetrics and gynaecology, surgery

Mayer-Rokitansky-Kuster-Hauser (MRKH) is a rare syndrome, with an estimated prevalence of 1 in 4500–5000 women, characterised by congenital absence of the superior portion of the vagina with variable development of the uterus.1 Although in the majority of cases the cervix and uterus are also absent, some women have an obstructed uterus with functional endometrium and other women have rudimentary uterine horns or Müllerian remnants. The low prevalence of this syndrome, in addition to the multiplicity of variants of uterine development, renders the diagnosis more challenging, even with standard imaging.1 2 Treatment-wise, laparoscopy has been the first option for surgical management of symptomatic uterine remnants; however, in order to provide a safe surgical approach, a careful and specific pre-operative evaluation should not be overlooked. There are few reports of specific uterine pathology in uterine remnants.3 4 The presence of uterine myomas and adenomyosis have been described,5 with the latter usually associated with uterine horns that retain a functional endometrium.6 We report a rare case of MRKH syndrome, with late worsening non-cyclic pelvic pain that prompted surgical treatment. Histological study revealed the exceedingly rare presence of adenomyotic foci in a uterine horn with no functional endometrium, challenging the most accepted theory on adenomyosis physiopathology. Case presentation A 37-year-old woman was referred by her primary healthcare physician to a gynaecology appointment in our centre. Her main previous health issues included a primary amenorrhoea diagnosed at 18 years of age, and MRKH syndrome. She presented with a 2-year history of worsening non-cyclic pelvic pain and dyspareunia, symptoms that were previously absent. She presented intermittent urine flow and no bowel compressive symptoms. At the time of her appointment, she had inadequate pain control with oral analgesia. General examination was unremarkable. She had a female phenotype, no signs of abnormal levels of testosterone (such as acne or hirsutism), normal facies and no webbed neck. She denied galactorrhoea. No other signs were suggestive of an alternative cause of primary amenorrhoea. Gynaecologic examination showed normal external genitalia, hypoplasic superior vagina and absence of the uterine cervix. Pubic hair and breasts were consistent with Tanner stage 4. At bimanual palpation, a vaginal narrowing towards the pelvic cavity could be identified, but the other gynaecologic organs were difficult to distinguish. Palpation of the left adnexal induced pain that was consistent with the patient’s complaints. Investigations When referred to our gynaecology department, the patient had already undergone investigation for her primary amenorrhoea and was deemed to have MRKH syndrome. However, no previous imagiological exams were available and there was no information about the absence or presence of either a uterine cervix or uterus body. On transvaginal ultrasound, the presence of a hypoplasic uterus with 4 cm length and a heterogeneous myometrium was reported. MRI revealed a left-rotated hypoplastic uterus, with 5 cm longitudinal length, heterogeneous, and the presence of fundic mass suggesting a 25 mm fibromyoma. Given these findings along with significant pelvic pain, dyspareunia and inadequate pain relief, we decided to perform a diagnostic laparoscopy. The patient was informed about an eventual hysterectomy or even adnexectomy based on intraoperative findings, to which she gave her informed written consent. Preoperative evaluation for urinary tract anomalies with a urography CT, showed no significant changes. Treatment Veress insufflation needle was placed in the umbilicus for pneumoperitoneum and three additional 5 mm ports were placed in the right and left iliac fossa and suprapubic region. Intraoperatively, a rudimentary uterine horn with 5 cm was found attached to the left pelvic wall through the round ligament; a smaller rudimentary uterine horn with 3 cm was found attached to the right pelvic wall through the right round ligament. Adjacent to the upper end of the blind vagina, an elongated fibrous formation was identified, joining both rudimentary horns. Normal ovaries and tubes were found bilaterally. Considering intraoperative findings and after evaluating the technical feasibility and safeness of the procedure, we decided to perform the removal of the formation as a whole including its central segment, for the possibility of being a contributor to her symptoms. Removal of this formation was performed by adapted standard laparoscopic procedure with bilateral salpingectomy. Clamping with bipolar energy and cutting was performed on round ligaments, mesosalpinx, vascular pedicles of the uterine remnants, uterine artery and cardinal ligaments. The central formation, previously described, was dissected from adjacent structures, including the bladder, and separated from the vagina without its opening. A minilaparotomy with 5 cm was necessary for the removal of the surgical specimen, which was excised as a whole (video 1) Outcome and follow-up Histological examination reported two rudimentary uterine horns, without any cavity. Numerous adenomyotic foci were found on the left rudimentary horn, across its whole thickness. This malformation was classified as U5a class of the ESHRE/ESGE (European Society of Human Reproduction and Embryology / European Society for Gynaecological Endoscopy) classification system of female genital anomalies. The patient had an uneventful postoperative recovery and was discharged 2 days after the surgical intervention. On a 6-week follow-up appointment, she presented with full remission of her symptoms (pelvic pain, dyspareunia and intermittent urinary flow).

MRKH syndrome is defined by vaginal agenesis, in the majority of cases accompanied by uterine agenesis. This condition, also known as Müllerian agenesis or Müllerian aplasia, is due to embryologic underdevelopment of the Müllerian duct and constitutes the second main cause of primary amenorrhoea.2 It has an estimated incidence of 1 in 4500–5000 females1 2 and the diagnosis is usually made during the investigation of primary amenorrhoea. When studied with MRI, rudimentary Müllerian structures are found in 90% of patients with MRKH. However, even if the absence of a normal midline uterus is easy to conclude, the interpretation and characterisation of uterine remnants are often difficult and misleading.2 Complications arising from the presence of uterine horns or other uterine remnants have been described in the literature.7–9 Regarding the symptoms, it is known that cyclic catamenial pelvic pain may be associated with rudimentary uterine horns due to functional endometrium and fluid accumulation into a closed space.10 Patients with this type of pain must be considered for surgical removal,11 12 knowing that the remission of pain is reported in an important percentage of cases where uterine remnants are removed.13 In our case, pelvic pain started only at 35 years of age, suggesting that this was not a case of catamenial pain. This characteristic symptom might have been a confounding factor for the correct diagnosis of uterine remnant associated pelvic pain, thus delaying the surgical treatment. In fact, the presence of myometrium in the uterine remnants, even with an absent functional endometrium, cannot exclude the coexistence of other uterine diseases. The presence of myomas3 4 14 and adenomyosis3 6 14 has been reported to occur in uterine remnants, although the latter rarely develops in rudimentary non-functioning uterine horns. We chose a laparoscopic approach, given the fact that it has been described as the treatment of choice for the removal of symptomatic uterine remnants in patients with MRKH.12 15 Removal of the uterine remnants remains a challenge, due to the unique anatomy and the lack of reproducibility of structures and anomalies among different patients. The experience of the surgeon, as well as the meticulous procedure at preoperative evaluation are important cornerstones to achieve a safe surgical resection.12 MRI must be performed systematically at preoperative evaluation as it is the gold standard when evaluating pelvic anatomy and uterine remnants. MRI also allows the assessment of abdominal anatomy and the dismissal of other sources of pelvic pain. In addition, it is compulsory to search for urinary tract anomalies, as MRKH syndrome is associated with urinary anomalies in 5.1%–34.2% of cases.1 16 17 Thus, CT urography was performed and revealed no signs of urinary anomalies. MRI urography should be considered instead of CT as it avoids radiation exposure. However, it is not readily available in our centre, and it would lead to an unfeasible waiting period for our patient. In our case, the major histopathological finding was adenomyosis through the full thickness of the left rudimentary horn. Adenomyosis is defined by the presence of endometrial glands and stroma within the myometrium, leading to hypertrophy of the surrounding myometrium. This was the only pathological feature found in the excised uterine horns. Clinical manifestations of adenomyosis frequently include abnormal uterine bleeding, uterine enlargement, pelvic pain and painful menses. The structural location of these findings in the pelvis was consistent with the pelvic pain described by our patient, suggesting that this could be the main cause for her symptoms. Concerning the fibrous band between the two rudiments, it did not show the presence of endometrium or adenomyosis, which is consistent with histological results obtained in previous studies. In this case, as it often occurs in MRKH syndrome, the imaging studies performed before surgery were not completely accurate. Therefore, we had to decide our surgical approach intraoperatively and we chose to perform the excision of the whole mass, including the fibrous band, as we were not sure at the time of its involvement in the genesis of our patient symptoms. This was a controversial decision, as this structure was exclusively fibrotic and its involvement in the development of pelvic pain has not been described previously in the literature. In our opinion, and considering our histological result, the removal of the two rudiments would have been sufficient and with lower risk of pelvic organ damage, which should be considered managing similar cases. Adenomyosis’ physiopathology remains elusive; it is widely accepted that adenomyosis is followed by the invasion of the endometrium into the uterine musculature, which is supported by the histological resemblance between normal endometrium and adenomyosis foci.18 However, this theory does not explain the presence of a uterine remnant with adenomyosis without functional endometrium. Some authors argue that the development of this condition is due to metaplasia of pluripotential stromal cells under the influence of autocrine and paracrine factors.19 20 This theory defends that adenomyotic lesions may arise de novo from metaplasia of displaced embryonic pluripotent Müllerian remnants or also from differentiation of adult stem cells.21 It is known that female reproductive tract develops during fetal life from the primordial embryological structures named Müllerian ducts22; metaplastic changes of embryonic pluripotent Müllerian remnants have been hypothesised to originate ectopic endometrial tissue in the myometrial wall, leading to the development of adenomyosis.3 21 23 In addition, populations of adult stem cells have been identified in the uterus, with some authors arguing that they may be responsible for the cyclic repair of endometrium after menstruation occurs.21 23 These cells could reach the uterus due to retrograde menstruation, differentiate into endometrial glands and stroma, and lead to the development of de novo intramyometrial adenomyotic lesions.21 The case here reported supports that ectopic endometrium hyperplasia may be independent of the presence of eutopic endometrium. Our report highlights the possibility of finding adenomyosis in a uterine horn even without functional endometrium. Also, we reinforce the need for a careful interpretation of imaging results, given not only the difficulty in assessing pelvic anatomy in patients with MRKH syndrome but also the fact that findings may be misleading. Learning points. Although Mayer-Rokitansky-Kuster-Hauser syndrome usually presents with uterine agenesis, up to 10% of the women may have an obstructed uterus or a rudimentary horn, which may also lead to other pathologies. A uterine remnant without functional endometrium may develop adenomyosis and lead to worsening pelvic pain and, consequentially, surgical treatment must be considered. Laparoscopic resection of uterine remnants should be the first therapeutic choice, which results in subsequent short recovery periods, low postoperative pain and good cosmetic results. Preoperative evaluation with MRI and MRI or CT urography is essential to assess the unique anatomy of these patients and to evaluate the presence of urinary tract anomalies. Footnotes Contributors: All authors have read and approved the manuscript. All authors contributed to the work according to ICMJE requirements for authorship. All authors declare that the manuscript is an original work that has not been submitted to another journal or conference. AMP was responsible for planning, conception, bibliographic research, reporting and design. ACS brought essential contributions and revised the manuscript. MO and NO supervised the whole work and revised the manuscript. Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy. Competing interests: None declared. Provenance and peer review: Not commissioned; externally peer reviewed. Ethics statements Patient consent for publication Consent obtained directly from patient(s).

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