A rare case of Mayer-Rokitansky-Kuster-Hauser syndrome with multiple leiomyomas in hypoplastic uterus.

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a rare disorder described as aplasia or hypoplasia of uterus and vagina due to an early arrest in development of mullerian ducts. Women with this syndrome are characterized by the presence of 46 XX karyotype, normal female secondary sex characters, normal ovarian functions, and underdeveloped vagina. The presence of leiomyoma in MRKH syndrome is very rare, and only few cases have been reported in the literature. Here, we report a case of MRKH syndrome with multiple leiomyomas originating from the rudimentary horn of uterus in 25 years married, phenotypically female patient.

INTRODUCTION

In clinical practice, one may encounter female patients with infertility which may be attributed to primary or secondary causes. In the group of primary infertility, congenital anomalies form relatively small but significant group. Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) is characterized by congenital absence of the uterus and vagina. There is a failure of development of the mullerian derivative of the vagina and the portions of the mullerian ducts that form the uterus. The incidence is 1 per 4000-10,000 female births.[1] The American Fertility Society classification, based on uterine anomalies is most commonly used to classify mullerian duct anomalies. Anomalies of vagina, tubes, and urinary bladder are described as associated malformations. This classification comprises seven classes.[2] MRKH syndrome is a class 1 mullerian duct anomaly, and it has been subdivided into typical or type A and atypical or type B.[3] Patients with type A syndrome have symmetric muscular buds, normal fallopian tubes. Patients with type B have asymmetric muscular buds, abnormal fallopian tubes, and may be associated with other congenital anomalies such as renal, skeletal, hearing, cardiac, and ocular anomalies. Familial distribution of these cases suggests the potential for a genetic link. Out of few genes which are identified in causation, one candidate is a mutation of the WNT4 gene, a developmental gene which regulates growth and differentiation during embryogenesis.[4] MRKH syndrome is the second most common cause of primary amenorrhea after gonadal dysgenesis. Women with this syndrome are characterized by the presence of 46 XX karyotype, normal female secondary sex characters, normal ovarian functions, and underdeveloped vagina. The presence of leiomyoma in MRKH syndrome is very rare, and only a few cases have been reported in the literature. Here, we report a case of MRKH syndrome (type A) with multiple leiomyomas originating from the rudimentary uterus.

CASE REPORT

Twenty-five years married female presented to the gynecology outpatient department with primary amenorrhea. There was no significant past history. Secondary sexual characters revealed the presence of pubic hair and axillary hair (Tanner stage 5) [Figure 1a]. Breast examination showed Tanner stage 2 [Figure 1b]. Per vaginal examination showed blind vagina. Uterus was not palpable. Investigations revealed normal intravenous pyelogram and a chromatin positive buccal smear. Ultrasonography examination showed agenesis of the uterus with right adnexal mass measuring 5 cm × 4 cm × 4 cm. Differential diagnosis of leiomyoma of the rudimentary uterus in MRKH syndrome includes ovarian fibroma, a gastrointestinal stromal tumor of the intestine and extravesical leiomyoma of the urinary bladder.[5] Magnetic resonance imaging showed hypoplastic uterus with right adnexal mass fibroid. The hormonal profile was within normal limits. Values were: Serum follicle stimulating hormone 7.17 mIU/mL; serum leutenizing hormone 15.6 mIU/mL; serum prolactin 10.64 ng/mL; and cancer antigen 125 4.5 IU/mL. With a provisional diagnosis of MRKH syndrome associated with right adnexal mass, she was taken for laparotomy. A rudimentary bicornuate uterus measuring 1.5 cm × 1.5 cm with a small cervix measuring 1 cm × 1 cm was found. A small collection of blood was noted which was drained. A total abdominal hysterectomy was performed in view of the presence of multiple nodules in a nonfunctional uterus. Specimen was sent for frozen section. Dye was seen in a slit-like an area endometrial cavity. Multiple myomertial nodules [Figure 1b] were seen arising from the rudimentary right and the left horns of the uterus [Figure 1c]. On cut section of the specimen, uterine horns were found noncommunicating, and they had a rudimentary endometrial cavity. All the nodules were well circumscribed, grayish white and had a characteristic whorled appearance. Histological examination revealed features of leiomyoma [Figure 1d] with rudimentary mullerian lining [Figure 1e]. The patient had an uneventful recovery and was advised vaginoplasty. She was discharged on the 7th postoperative day.

Figure 1

(a) Clinical photograph showing axillary hairs and normal breast development. (b) Gross photograph showing multiple leiomyomas in a hypoplastic uterus. (c) Rudimentary uterine horn with bilateral fallopian tubes. (d) Microphotograph showing leiomyoma (H and E, ×100). (e) Microphotograph showing rudimentary mullerian lining surrounded by smooth muscle

DISCUSSION

MRKH syndrome is characterized by the absent or hypoplastic uterus and vagina. Failure of fusion and development of mullerian ducts results in muscular thickening at the proximal end of each tube that are joined in the midline by a visible and palpable cord resembling hypoplastic bicornuate uterus without an endometrial lining.[6] Rarely, an active endometrium can exist with uterine analog, which becomes active in the presence of well-estrogenized state. In literature, it is mentioned that fibroids and adenomyosis rarely develop in the rudimentary nonfunctioning uterus.[7] Cytogenetic abnormalities in the form of spontaneous chromosomal rearrangements are known to occur in uterine leiomyomas. These chromosomal arrangements may be responsible for the initiation and progressive growth of the leiomyomas.[8] The leiomyomas are found to have higher concentration of estrogen receptors as compared to normal myometrium. These might explain the propensity to develop leiomyoma in the presence of exogenous and endogenous estrogen.[9] As the proximal ends of mullerian ducts have smooth muscles, the presence of leiomyoma in a case of mullerian agenesis is a theoretical possibility.[8] However, the occurrence of multiple leiomyomas in a rudimentary uterine bulb has been rarely reported earlier.[1011] The possible reason for this uncommon occurrence could be a decreased concentration or sensitivity of the estrogen receptors or a lesser genetic predisposition for the clonal chromosomal abnormalities that are observed in women with normal uterus with leiomyomas.[8] In our patient, we could not perform cytogenetic and receptor studies to point out the exact etiopathogenesis of this unique occurrence of multiple leiomyomas in the rudimentary uterine bulbs. Hysterectomy was performed in our case in view of nonfunctioning uterus and risk of recurrence after myomectomy. Treatment for patients of MRKH syndrome with leiomyoma is myomectomy or hysterectomy and vaginal reconstruction (vaginoplasty). There are many types of vaginoplasty – Frank's dilatation method, Williams vaginoplasty, Vecchietti procedure, Abbe-McIndoe vaginoplasty and Davydov technique. With advances in minimal access surgery, the Vecchietti and Davydov procedures can now be performed laparoscopically. The patients need psychological and social counseling. Reassurance and vaginoplasty should be done for a better life in such patients. Psychological counseling is important to emphasize the fertility potential. The ovarian function is normal in these patients so that ovum can be retrieved and with the help of a surrogate mother, it is possible to have fertility potential.

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Conflicts of interest

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