The reproductive abnormalities of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome are due to the incomplete development of the müllerian duct.1 This structure in the embryo develops into the uterus, fallopian tubes, cervix, and the upper part of the vagina.1 There are 3 different forms of this syndrome: the typical form is characterized by the congenital absence of the uterus and upper vagina with normal ovaries and fallopian tubes.1,2 The atypical form of MRKH syndrome may be associated with malformations of the ovaries or renal dysfunction. The third form was suggested as uterovaginal aplasia/hypoplasia, renal dysfunction with other congenital anomalies such as renal, skeletal, hearing, cardiac, and ocular anomalies, also known as MURCS syndrome.1,2
Mayer‐Rokitansky-Küster-Hauser syndrome affects approximately 1 in 5000 newborn girls.2 Unilateral renal anomalies are associated with 30% to 50% of MRKH patients.3,4 The etiology behind the abnormal development of the müllerian duct remains unknown.5 Both genetic and nongenetic etiologies have been suggested in the literature, although a complete understanding of MRKH syndrome remains elusive.3,5–10
A uterine fibroid, also known as leiomyoma, is a benign tumor arising from the myometrial layer. Fibroids affect 7% of white women who have an otherwise normal uterus. Malignant transformation is rare at 0.2% to 0.3%.11 The presence of fibroids has been described in MRKH patients, as it can develop from the rudimentary uterus.12–15 The occurrence of a fibroid in a woman with a congenitally absent uterus with MRKH has not been described in the white population. Here, we describe the first such case of an ectopic fibroid that developed in a 66-year-old white woman with a congenitally absent uterus and MRKH syndrome with unilateral renal agenesis.
A 66-year-old woman with MRKH syndrome presented with chronic right-lower-quadrant abdominal pain and recurrent urinary tract infections. The patient’s medical history suggested a congenitally absent uterus and a unilateral right kidney. A renal sonogram confirmed the presence of a solitary right kidney (Fig. 1). Further transabdominal and endovaginal ultrasound (US) scans demonstrated the absence of a uterus (images not shown). Neither ovary nor ovarian-like structures were identified with certainty. A solid vascular lesion was incidentally discovered adjacent to the superior right lateral aspect of the urinary bladder (Fig. 1). This measured approximately 5 cm in maximum dimension with subtle internal vascularity on color Doppler analysis (Fig. 1). It displayed both echogenic and hypoechoic components in a nonspecific manner (Fig. 1). This structure did not appear to be particularly mobile on endovaginal probe palpation. No ascites was identified. At this point, the differential diagnosis was broad and included (but not limited to) an ectopic fibroid, a solid ovarian mass, a gastrointestinal stromal tumor (GIST), a bladder wall lesion, or a developmental abnormality including abnormal ectopic uterine tissue or ectopic kidney. Therefore, further investigation with magnetic resonance imaging (MRI) was recommended.
Magnetic resonance imaging confirmed the presence of a pelvic mass, to the right of midline, and confirmed the absence of either normal ovary or uterus (Fig. 2). The mass was isointense to normal expected myometrium on T1-weighted images and had low-signal intensity on T2-weighted images, with the MRI appearance of a nondegenerated fibroid containing smooth muscle. Postgadolinium images demonstrated enhancement (Fig. 2). The MRI scan showed that the mass was separate from the bladder but was in contact with several surrounding small bowel loops. Further evaluation with an intravenous contrast-enhanced abdominal and pelvic computed tomography (CT) scan was recommended to delineate the lesion’s relationship to surrounding small bowel. The subsequent CT scan showed that the mass was not arising from surrounding loops of small bowel (Fig. 3), which made a GIST unlikely. With a provisional diagnosis of MRKH syndrome and a right pelvic mass of uncertain etiology, the patient underwent a laparotomy. A 4.5 × 4-cm well-circumscribed mass was found relatively close to the right round ligament with suspicion of blood supply originating from the region of the expected right ovary. Streak gonads were identified, tacked up high along the paracolic gutters bilaterally. Despite laparoscopic exploration, a uterus was not identified. The mass was laparoscopically excised along with the streak gonads. Normal uterine tissue was absent on histological sectioning of the excised mass. No müllerian duct remnant could be identified pathologically either. The histopathology report confirmed the smooth muscle nature of the lesion. On immunochemistry staining, the cells were strongly positive for actin and desmin. Furthermore, immunochemistry studies also confirmed that the cells had negative staining for CD117 (GIST marker), CD34 (a marker of hematopoietic progenitor cells), and S100 (neurological tumor marker). Therefore, a final diagnosis of a fibroid without a uterus was confirmed in this 66-year-old patient with MRKH syndrome. No evidence of a pelvic malignancy or pelvic metastatic disease was identified.
Mayer‐Rokitansky-Küster-Hauser syndrome is a rare disease featured as aplasia or hypoplasia of the uterus due to the agenesis of the müllerian ducts. Few cases of fibroids associated with MRKH syndrome have been reported in the literature. Our literature search revealed only 15 case reports, including the present one, since 2000. The characteristics of the series of cases are summarized in Table 1. The ages of the patients ranged from 20 to 70 years, and most of the patients were younger than 60 years. All cases were reported outside the Unites States or Canada. Four cases had a solitary kidney. The majority of cases had either a bilateral or unilateral rudimentary horn of hypoplastic uterine remnants. Only 2 other cases, occurring in Ethiopia and Jamaica respectively (Table 2), did not identify a uterus through their various investigations.4,21
Diagnosis of MRKH syndrome is usually made in adolescence during a workup for primary amenorrhea. Imaging workup of MRKH syndrome includes US, CT, or MRI, which can identify the absent or hypoplastic uterus, cervix, and vagina.24–28 However, neither US, CT, nor MRI is sensitive to definitively exclude remnant uterine tissue with certainty. When reviewing the literature, only 4 cases using MRI identified a rudimentary uterine remnant with MRKH syndrome (Table 2). In most cases, the types of uterine malformation with MRKH syndrome were confirmed during surgery or the postoperative pathologic analysis (Table 2). Patients with a pelvic fibroid with an undiagnosed, congenitally absent uterus pose a diagnostic dilemma. This was highlighted in the case described by Fletcher et al,21 where the MRI appearance of a fibroid was mistaken for an ectopic uterus, particularly because the cystic degeneration of a fibroid can mimic the appearance of an endometrial cavity of an ectopic uterus on MRI.21 It is important that the interpreting radiologist be aware of this potential diagnostic pitfall. In our case, US was the first modality used to assess the patient’s clinical complaint. We were able to identify a fibroid-like mass in the pelvis and confirm the absence of a uterus or uterine remnant. Thus, in the context of MRKH syndrome, US could provide very useful information in patient workup. Our case highlights that, even with an apparent congenitally absent uterus, a fibroid should still be suspected in a woman with MRKH and a pelvic mass of uncertain etiology.
The etiology behind the abnormal development of the müllerian duct remains unknown.5 Originally, researchers believed that MRKH syndrome was caused by environmental factors, such as teratogenic exposure to medications during pregnancy or maternal illness.6 This nongenetic etiology hypothesis was further endorsed by a report where only 1 monozygotic twin received a diagnosis of MRKH syndrome.3,7,8 An increasing number of cases with familial occurrence of MRKH syndrome have been subsequently revealed. The familial genetic clustering study demonstrated a list of candidate gene targets potentially involved in the syndrome, such as such as pre–B-cell leukemia homeobox 1 gene (PBX1), a subset of homeotic family genes (HOX), WNT family genes, and antimüllerian hormone gene (AMH).5,9,10 These led to the hypothesis of a genetic etiology. Currently, a complete understanding of MRKH syndrome remains elusive and controversial.
Leiomyomas are benign tumors arising from the myometrial layer of the uterus and contain fibromuscular tissue made up of smooth muscle cells. Estrogen stimulates fibroid growth, whereas progesterone inhibits growth.11 Because most MRKH patients still maintain normal ovarian function with normal levels of estrogen and progesterone, fibroids in these patients undergo the same evolution as those in a normal uterus. It is conceivable that fibroids develop in patients with MRKH who have a hypoplastic uterus, because myometrial tissue could still be present to allow fibroids to arise.29 When the uterus is congenitally absent as in uterine agenesis, how a fibroid may arise is more difficult to conceive. It should be noted, however, that the proximal ends of the müllerian ducts have smooth muscle cells, which could explain the etiology of fibroids even when the uterus itself is absent. Other potential etiologies for this rare occurrence could be an increased concentration or sensitivity of estrogen receptors in remnant myometrium tissue responsible for exogenous and endogenous estrogen secreted by ovaries. Alternatively, additional somatic genetic mutations or clonal chromosomal abnormalities contributing to different levels of regulators of estrogen signaling may also occur in MRKH patients with fibroids.12 The utilization of genome-wide approaches by next-generation sequencing will be a valuable tool in investigating the genetics of MRKH syndrome and the etiology of a fibroid associated with this syndrome.
Overall, the presence of fibroid in an absent uterus is extremely rare, but it is important that the radiologist is aware of this entity so that a fibroid can be considered in the differential diagnosis of a pelvic/lower abdominal mass even if no apparent uterine tissue can be appreciated.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available, upon request, for review by the editor-in-chief of this journal.
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