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Title: A rare case of male pseudohermaphroditism-persistent
mullerian duct syndrome with transverse testicular ectopia –
Case report and review of literature
Authors: Aashish Rajesh, Mohammed Farooq
PII: S2210-2612(17)30269-9
DOI: http://dx.doi.org/doi:10.1016/j.ijscr.2017.06.016
Reference: IJSCR 2577
To appear in:
Received date: 15-3-2017
Revised date: 1-6-2017
Accepted date: 5-6-2017
Please cite this article as: Rajesh Aashish, Farooq Mohammed.A rare case of male
pseudohermaphroditism-persistent mullerian duct syndrome with transverse testicular
ectopia – Case report and review of literature.International Journal of Surgery Case
Reports http://dx.doi.org/10.1016/j.ijscr.2017.06.016
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TITLE
A RARE CASE OF MALE PSEUDOHERMAPHRODITISM-PERSISTENT
MULLERIAN DUCT SYNDROME WITH TRANSVERSE TESTICULAR
ECTOPIA- CASE REPORT AND REVIEW OF LITERATURE
Author information:
1. Aashish Rajesh (MBBS)madras medical college, chennai
2. Mohammed Farooq MBBS, (MS)madras medical college, chennai
Institution: Madras Medical College, No.3 EVR Periyar Salai, Egmore, Chennai-
600003, Tamil Nadu, India
Corresponding author details:
Aashish Rajesh,
B1401, The Atlantic,
No.3 Montieth Road,
Egmore, Chennai – 600008
Telephone number – +919566196186
Email id- ashish747raj@gmail.com
Highlights:
Herniotomy and bilateral orchidopexy is recommended for TTE-PMDS
No reports suggest malignancy from the mullerian structures
Division of mullerian structures is done only if it interferes with orchidopexy
Malignancy may arise in the testis though histologically normal
ABSTRACT
INTRODUCTION:
Persistent Mullerian duct syndrome (PMDS) is a rare type of male
pseudohermaphroditism. Transverse testicular ectopia (TTE) is characterized by one
testis moving to the opposite side and both testes traversing the same inguinal canal.
CASE PRESENTATION:
An 11-month-old boy presented with bilateral cryptorchidism. The left testis was not
palpable; the right testis was canalicular with a right inguinal hernia. Ultrasound showed
both testes located in the right inguinal canal. Right inguinal exploration revealed two
testes with intact spermatic cords. A primitive uterus with fallopian tubes was also
identified on opening the processus vaginalis. After herniotomy, bilateral orchidopexy
was carried out (left orchidopexy through a trans-septal approach). Karyotyping
confirmed a male gender (46XY). One year after the operation, ultrasound showed both
testes to be in good condition.
DISCUSSION:
PMDS is caused by defects in the gene that encodes Antimullerian hormone(AMH).
Treatment aims to correct cryptorchidism and ensure appropriate scrotal placement of the
testes. Malignant transformation is as likely as the presence of abdominal testes in an
otherwise normal man. Failing early surgical correction, gonadectomy must be offered to
prevent malignancy. Division of the persistent mullerian duct structures is indicated only
in patients where persistence interferes with orchidopexy.
CONCLUSION:
TTE should be suspected in patients presenting with inguinal hernia on one side and
cryptorchidism on the other side. Herniotomy and bilateral orchidopexy is optimal.
Removal of mullerian structures may injure the artery to vas deferens and is hence not
recommended. Follow-up for fertility assessment in the latter years should be counselled.
KEY WORDS
Persistent mullerian duct syndrome; transverse testicular ectopia; testis; cryptorchidism;
orchidopexy; case report
BODY OF THE ARTICLE
INTRODUCTION:
Persistent Mullerian duct syndrome (PMDS) occurs in a phenotypic and genotypic male
who has a concurrent uterus, fallopian tubes, and an upper vagina as the mullerian ducts
fail to regress. In transverse testicular ectopia (TTE), one of the testes moves to the
opposite side and both testes pass the same inguinal canal. The concurrence of TTE and
PMDS is extremely rare.
We report a patient with PMDS and TTE who presented with a right-sided inguinal
hernia and left undescended testis. This child was managed in our tertiary care institution.
This report highlights the pathogenesis and management of PMD and TTE, the possible
complications of dividing these structures and the necessity for fertility follow-up and
gonadectomy in certain situations.
PATIENT INFORMATION: An 11-month-old boy was brought by his mother to our
hospital for evaluation of bilateral cryptorchidism.
CLINICAL FINDINGS: The left testis was impalpable, the right testis was canalicular
and a right inguinal hernia was present.
TIMELINE:
Cryptorchidism was detected by the caregivers only at 11 months and the patient was
brought in.
DIAGNOSTIC ASSESSMENT:
Ultrasound revealed a small left and a larger right testis, both located in the right inguinal
canal. Karyotyping was 46XY.
THERAPEUTIC INTERVENTION:
An inguinal exploration was planned to correct the cryptorchidism. Pre-operative
assessment and anesthetic clearance was obtained. The surgery was performed under
general anesthesia with caudal block by a senior pediatric surgeon. Right inguinal
exploration revealed bilateral testes with intact spermatic cords and a sac in the right
inguinal region suggesting transverse testicular ectopia(Fig.1). When the processus
vaginalis was opened, a primitive uterus together with fallopian tubes was identified
confirming the presence of persistent mullerian duct syndrome (Fig.2,3). After
performing herniotomy, bilateral orchidopexy was carried out (left orchidopexy through a
trans-septal approach). The mullerian structures were not divided to prevent injury to
vessels supplying the testes and vas deferens. The patient was discharged the following
day. Sutures were removed on the 10th postoperative day and no apparent complications
were detected.
FOLLOW-UP AND OUTCOMES:
Postoperative follow-up was uneventful. One year after the operation, ultrasound showed
both testes to be in good condition.
DISCUSSION:
An ectopic testis is one which is found in a location not along the standard path of
testicular descent. This differentiates this anomaly from an undescended testis. Crossed
or transverse testicular ectopia was first described by Von Lenhossek in 1886.1TTE is
characterized by both testes descending through a single inguinal canal and being on the
same side with contralateral cryptorchidism.
The exact number of documented cases of TTE till date has not been reported. Fourcroy
et al summarized that about 100 cases of TTE had been reported till 1982.2 Our PubMed
search identified 152 cases published after 1982 bringing the number of reported cases to
about 260 till date
TTE associated with PMDS is extremely rare and Ferri et al state that 10 cases had been
reported till 1999.3 Review of the PubMed database using ‘persistent mullerian duct
syndrome with transverse testicular ectopia’ identified 47 more cases since 1999. Thus, to
our knowledge there are only 57 reported cases of TTE with PMDS till date.
Various anatomic factors (defective implantation, rupture or tearing of the gubernaculum,
obstruction of the internal inguinal ring, adhesions between the testis and adjacent
structures, late closure of the umbilical ring, etc.) are suggested as causative factors in the
failure of testicular descent.5
TTE has been classified as three types: Type I accompanied by hernia (40-50%),Type 2
by persistent or rudimentary mullerian duct structures (30%) and Type 3 associated with
disorders such as hypospadias, pseudohermaphroditism and scrotal abnormalities.
TTE patients sometimes have associated PMDS. Mullerian structures include fallopian
tubes, uterus and the upper part of the vaginal canal. PMDS is characterized by the
persistence of these structures in their primitive form in male children.
PMDS is caused by defects in the gene that encodes the synthesis or action of Mullerian
inhibiting Factor or Antimullerian hormone.5-8 AMH is secreted by the sertoli cells of the
developing testes by 7 weeks of gestation. The other cause of persistence of Mullerian
ducts, testicular dysgenesis, usually affects both Sertoli and Leydig cells. Persistence of
Mullerian derivatives is then associated with external genital ambiguity.
Soon after testicular differentiation, AMH gene expression is induced by SOX9 in sertoli
cells which results in an ipsilateral regression of the mullerian ducts by 8 weeks of
gestation, before the emergence of testosterone secretion or the stimulation of the
wolffian ducts.9
The gene encoding AMH I is located in the short arm of chromosome 19(19p13.3). AMH
signaling is mediated via a heterodimeric receptor consisting of type 1 and type 2
serine/threonine kinase receptor, the type 2 part of the receptor mediates ligand
specificity and the type 1 receptor activates a downstream signaling cascade. ALK 2,
ALK 3 and ALK 6 have all been linked to type 1 signaling and decreased expression or
deletion of the former two disrupts mullerian duct regression.10 The type 2 receptor is
called as AMHR2 and is located on chromosome 12(12q13). AMH mutations are often
autosomal recessive. Affected patients usually have an AMH gene mutation in 45%, and
in the AMRH2 receptor gene in another 39%. In the remaining 15%, no mutation was
detected, implicating genes coding for other factors in the AMH transduction
cascade.11AMH and AMH2 receptor mutations are transmitted through an autosomal
recessive pattern and are symptomatic only in males.
Female sexual development is not affected as AMH is not expressed during sexual
differentiation in female fetuses. Lack of AMH promotes mullerian proliferation in
females. In males, an absent AMH or its receptor prevents normal Müllerian duct
regression and hence the child has both the urogenital ridges containing the Wolffian and
the Mullerian ducts. So in addition to normal wolffian duct differentiation structures like
the epididymis, vas deferens and seminal vesicles, there is a hypoplastic female genital
tract. Neonates present with male external genitalia with normal development of the penis
and scrotum, but with cryptorchidism.
There are 3 clinical presentations of PMDS: (Fig.4)
a. Testes in normal position of ovaries and inguinal sac empty (60-70%)
b. One testis in an inguinal hernia with attached tube and uterus (Hernia uteri
inguinalis) (20-30%)
c. Both testes herniated into one processus vaginalis (Transverse testicular ectopia)
(10%)
In the first presentation, patients have bilateral impalpable intra-abdominal testes with
retained Müllerian ducts that are identified on investigation often by laparoscopy.12 The
second presentation is characterized by hernia uteri inguinalis, in which a boy with
unilateral cryptorchidism and an ipsilateral inguinal hernia is found to have a Fallopian
tube with the testis inside the hernial sac. In the third type, the boy presents with
cryptorchidism with an inguinal hernia that contains both the testes, Wolffian ducts and
Müllerian ducts, which is known as transverse testicular ectopia. The cause of
cryptorchidism and transverse testicular ectopia in PMDS is thought to be due to an
abnormally long gubernacular cord, which is similar to a long round ligament in the
uterus.13 This excessive mobility of the intra-abdominal testes caused by a long
gubernacular cord leads to a high incidence of gonadal torsion in patients with PMDS, so
that there is a notably increased risk of testicular atrophy.14
Some researchers have suggested that the putative mechanism for cryptorchidism in
PMDS is a simple passive inhibition of testicular descent by the retained Müllerian
ducts.15The mobility of the testes and frequency of torsion is strong evidence against the
theory of retained Müllerian ducts passively blocking testicular descent.
PMDS is mostly discovered during surgery for inguinal hernia or for cryptorchidism. In
all patients with inguinal hernia and cryptorchidism, an ultrasound evaluation must be
considered to identify possible TTE and PMDS. TTE and PMDS patients have normal
karyotype.
Treatment of PMDS is exclusively surgical and aims to correct cryptorchidism. The
testes are usually histologically normal, though the germinal cells may be affected due to
long-standing cryptorchidism. The overall incidence of malignant transformation in these
testes is 18%, similar to the rate in abdominal testes in otherwise normal men. There have
been reports of embryonal carcinoma, seminoma, yolk sac tumor and teratoma in patients
with PMDS16. Early surgical intervention is necessary for testicular preservation, failing
which gonadectomy must be offered to prevent malignancy.17Adequate surgery involves
bilateral orchidopexy.
The division of the persistent mullerian duct structures is controversial as it may damage
the artery to the vas deferens and is not advocated unless persistence interferes with
orchidopexy. The testis can also be crossed across the root of the penis in the inguinal
region and descended through the ipsilateral inguinal canal instead of going for a trans-
septal approach of placing the contralateral testis.18 Retroperitoneal transposition of the
gonad can be done when the cord length does not permit trans-septal orchidopexy.19 Early
surgery promotes gonadal function and prevents subfertility.
TTE is a rare condition and should be suspected in patients presenting with inguinal
hernia on one side and cryptorchidism on the other side. Optimal surgical approach
should include herniotomy and bilateral orchidopexy. There are no reports of malignancy
arising from Mullerian remnants and due to the risk of injuring the blood supply of testes
and vas deferens, the removal of these structures is no longer recommended. A long-term
follow-up is needed for the assessment of fertility in these patients.
Consent
Written informed consent obtained from the patient's mother
Author contribution
Aashish Rajesh - Drafting the manuscript, revision, approval of final version
Mohammed Farooq - Performing surgery, revision , approval of final version
sources of funding
No funding received
Registration of Research Studies
Not applicable
Guarantor
Aashish Rajesh
PATIENT PERSPECTIVE:
The patient’s mother felt relieved with the surgical result.
INFORMED CONSENT:
This publication is subsequent to a documented consent from the patient’s mother after
adequate explanation and assurance of anonymity.
ADDITIONAL INFORMATION:
CONFLICT OF INTEREST:
The authors have no conflict of interest to reveal
SOURCE OF FUNDING:
This report did not receive any funding
ETHICAL APPROVAL:
Not applicable
This case report has been reported in line with the SCARE criteria.20
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Legend for figures:
Fig.1- Both testes in right inguinal hernia
Fig.2- Tubes and Uterus (Primitive) clearly seen
Fig.3- TTE with PMDS
Fig.4- 3 clinical presentations of PMDS
