Persistent Mullerian duct syndrome: rare presentation in an elderly man

Abstract

Persistent Mullerian duct syndrome has been described as a disease of internal male pseudohermaphroditism, a rare autosomal recessive disease, characterised by persistent Mullerian derivatives in patients with male pattern 46, XY karyotype and normal pattern virilisation. We present a case of an elderly man, who on evaluation for bilateral undescended testes was found to have a pelvic mass suggestive of malignant transformation of an undescended testis on imaging. On surgical exploration, uterus with multiple fibroids, bilateral fallopian tubes, cervix and bilateral atrophic testes were identified. Interestingly, in this case, imaging (contrastCT and MRI) had missed Mullerian structures due to varied presentation, but exploration and excision of the structures followed by their histopathology revealed uterine leiomyomas and confirmed other Mullerian structures (bilateral fallopian tubes, cervix) with bilateral testes.

Background

Commonly, persistent Mullerian duct syndrome (PMDS) presents in childhood. Presentation can be varied in the form of inguinal hernia, undescended testes and so on or can be totally asymptomatic. Through our case, we attempt to put across that the presence of persistent Mullerian structures in an adult married man is possible and should be considered as a differential diagnosis in patients with undescended testes, irrespective of their age.

Case presentation

A 56-year-old, married, South Indian Tamil man presented to the urology outpatient department with a history of gynaecomastia for 3–4 months and lower abdominal pain for 1 month. On general examination, the patient had bilateral gynaecomastia and well-developed secondary sexual characters. On abdominal examination, a single 7×6 cm hard mass with nodular surface and diffuse margins was palpable in the suprapubic region. On genital examination, he had a normal penis. Bilateral scrotal sacs were well developed, had rugosities but were empty. Both testes were not palpable in either inguinal regions or per abdominally (figure 1).

Figure 1.

Clinical examination revealed bilateral gynaecomastia and well-developed secondary sexual characters. Normal penis, bilateral scrotal sacs were well developed, had rugosities, but empty. Testes were not palpable in either inguinal regions or per abdominally.

The patient was phenotypically male with normal external genitalia and secondary sexual characteristics were present. The patient had a history of primary infertility, which had not been evaluated in the past. He has an adopted offspring who is now an adult. The patient was offered endocrine evaluation for gynaecomastia and infertility workup. However, as he was not planning on having another child, he denied the same.

Investigations

Serum-free testosterone levels were within normal limits (56.26 pg/mL). On contrast-enhanced CT of the abdomen and pelvis, an 8.4×7.8×6.2 cm homogenous lobulated soft tissue density mass lesion, was seen in the pelvis in the rectovesical region. The lesion showed post contrast heterogenous enhancement. The lesion resulted in displacement of adjacent bowel loops and urinary bladder anteriorly. It derived its blood supply from the left internal iliac artery. A small soft tissue density poorly enhancing focus measuring 1.2×1.0 cm was also seen in the retroperitoneum adjacent to right psoas suggestive of atrophic right testis. These findings on imaging gave an impression of a right atrophic testis and a testicular neoplasm from cryptorchid left testis (figure 2).

Figure 2.

ContrastCT of the abdomen showed 8.4×7.8×6.2 cm homogenous lobulated soft tissue density mass lesion seen in the pelvis in rectovesical region. Lesion showed post contrast heterogenous enhancement. The lesion caused displacement of adjacent bowel loops and urinary bladder anteriorly. The lesion derived its blood supply from left internal iliac artery.

An MRI of the abdomen was also done, which concluded the same (figure 3).

Figure 3.

An MRI of the abdomen showed similar findings plus a small soft tissue density poorly enhancing focus measuring 1.2×1.0 cm seen in the retroperitoneum adjacent to right psoas suggestive of atrophic right testis. These findings gave impression of right atrophic testis and testicular neoplasm from cryptorchid left testis.

Tumour markers including beta-human chorionic gonadotropin, alpha-fetoprotein and lactate dehydrogenase were within normal limits (<0.1 mIU/mL, 1.51 IU/mL and 178 U/L, respectively).

Treatment

Based on clinical and radiological findings, the patient was taken up for laparotomy. Intraoperatively, we encountered uterus, cervix with bilateral fallopian tubes and both atrophic testes (figure 4).

Figure 4.

Surgical specimen photo of uterus and atrophic testicles.

Excision of these Mullerian duct remnants and both atrophic testes was carried out. Histopathology revealed that uterus having multiple leiomyomas, fallopian tubes showing normal features and atrophic testes with Leydig cell hyperplasia (figure 5).

Figure 5.

Histopathology with H&E staining confirmed the organs as uterus having multiple leiomyomas (×40 magnification) with normal endometrial glands (×100 magnification), fallopian tubes (×40 magnification) and both atrophic testes (×40 magnification).

As per patient family’s wish, no further evaluation or treatment was sought.

Outcome and follow-up

Postoperatively, the patient recovered well and as per family’s wish further genetic counselling and karyotyping were deferred.

Discussion

PMDS is a rare form of internal male pseudohermaphroditism, caused by a defect in either the production or in the end-organ response to anti-Mullerian hormone (AMH). PMDS patients have been found to possess mutations of the Mullerian inhibiting substance (MIS) gene or the MIS type II receptor gene with autosomal recessive transmission.¹ In a normal male fetus, sertoli cells produce AMH, which results in regression of Mullerian ducts in autocrine and paracrine manner.² Patients with PMDS are karyotypically and phenotypically male with well-developed external genitalia and normally developed secondary sexual characteristics.^3–6

PMDS has three known anatomical variants.⁷ Types I and II are the commoner, male forms of PMDS, whereas type III is female form. Type I (male type), also known as ‘hernia uteri inguinalis’, has an incidence of 60%–80% and is characterised by the presence of testis in scrotum or in the inguinal canal, which can be brought down by gentle traction. As the name suggests, type I also presents with herniation of the ipsilateral corner of the uterus and the ipsilateral fallopian tube along with testis into the inguinal canal. Type II (male type), also known as ‘transverse testicular ectopia’, is characterised by herniation of both testes, entire uterus and both fallopian tubes. It is the second most common type with an incidence of 20%–30%.^7–9 Type III, with an incidence of 10%–20%, is the female form of PMDS, which is characterised by bilateral cryptorchidism, testes fixed within the round ligaments assuming an ‘ovarian position’ with respect to the uterus.^{8 9} It has been noted that the mobility of the Mullerian structures is also an important factor in the various clinical presentations of PMDS.^{7 9} Freely mobile uterus and fallopian tubes may be pulled into the inguinal canal during testicular descent, or, if these Mullerian structures are relatively fixed, testicular descent may be impeded.^{7 9–11}

Our patient had bilateral cryptorchidism without inguinal or scrotal hernia at presentation, thus suggesting immobility of Mullerian structures. Hence, based on both these findings, the patient can be classified into the rarer type III female variant.

The risk of malignant transformation in ectopic testis of patients with PMDS is similar to that of a cryptorchid testis in any other healthy man.¹² Undescended/ectopic testis may develop germ cell tumours, but tumours of the Mullerian duct derivatives per se are very rare with a 3.1%–8.4% risk of developing a tumour from the remnants.^{13 14}

Various management strategies have been described for PMDS. In cases with no suspicion of malignancy, orchidopexy with excision of Mullerian remnants can be done while avoiding damage to blood supply to the vas.^{15 16} Stripping/destroying the mucosa of the retained Mullerian remnants to reduce the risk of malignancy has also been described as a more conservative way of management, which simultaneously prevents damage to the vas deferens and disruption of collateral blood supply to the testes.² In this case, the patient had multiple uterine fibroids with bilateral atrophic testes and hence Mullerian remnants along with bilateral testes were excised.

Patient’s perspective.

I consulted a doctor after feeling slight discomfort and occasional pain in my lower abdomen. I also felt heaviness in both breasts for past couple of months. During consultation and examination, doctor asked me about personal life, relationship with wife and kids. I revealed that I never had testicles in scrotum, we had an adopted son who is an adult at present, wife being aware of my condition and adoption was a common decision. For further investigations, I was asked to undergo CT scan, which showed possibility of tumour in my abdomen. After another MRI scan, I was explained that there is possibly tumour arising from one of my testicles, which are in my abdomen! After other blood tests, doctors advised me to undergo operation and removal of the tumour. I was explained possibility of requirement of removing both testicles if found abnormal or non-functioning. We discussed at home and I came after about a week for admission. Before operation, hospital stay was smooth and I underwent operation in the next day morning. I woke up after approximately 5–6 hours post procedure. My wife met me first and in front of her my team of doctors came to see me. They explained that they had removed the tumour but they have suspicious of some abnormal organs like uterus and fallopian tubes inside my abdomen! All the abnormal organs along with both testicles which were non-functioning were removed and sent for biopsy. This was real shocker to me and my wife. We were not able to understand how this can be possible. Our team of doctors slowly explained to us about my condition, possible causes, complications, similar cases in the world, prognosis and future implications. I recovered well after operation and was discharged after 2 days of hospital stay. My sutures were removed after 10 days and biopsy report was also ready by then. Doctors explained that biopsy has confirmed organs as uterus and fallopian tubes, both testes were non-functioning and tumour was arising from the uterus, which was benign. They advised me some genetic tests also. After discussion with my wife, we decided not to go for further tests as they would not change anything and we had decided not to involve our son in the process, he has not been informed about biopsy report and abnormal organs inside my abdomen. Doctors were with us in our decision and we were explained about good prognosis. I consider this whole experience a bit shocking, but had good support of my wife throughout and doctors helped we with counselling, postoperative care and helped us understanding facts and about the condition we were going through.

Learning points.

• Persistent Mullerian duct syndrome should be kept in mind while dealing with a case of bilateral undescended testes, even in an elderly patient.

• Contrast-enhanced CT and MRI can miss the diagnosis due to varied presentation of Mullerian structures.

• Diagnostic laparoscopy may help in such cases of diagnostic dilemma.