Accepted Manuscript Persistent Mullerian Duct Syndrome presenting as irreducible inguinal hernia – A surprise surgical finding! V. Sekhon, M. Luthra, G. Jevalikar PII:
S2213-5766(16)30206-8
DOI:
10.1016/j.epsc.2016.11.002
Reference:
EPSC 660
To appear in:
Journal of Pediatric Surgery Case Reports
Received Date: 20 October 2016 Accepted Date: 5 November 2016
Please cite this article as: Sekhon V, Luthra M, Jevalikar G, Persistent Mullerian Duct Syndrome presenting as irreducible inguinal hernia – A surprise surgical finding!, Journal of Pediatric Surgery Case Reports (2016), doi: 10.1016/j.epsc.2016.11.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title Persistent Mullerian Duct Syndrome presenting as irreducible inguinal hernia – A surprise surgical finding!
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Abstract
Persistent Mullerian Duct Syndrome(PMDS) is diagnosed as a discrepancy between
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masculine external genitalia and female internal genitalia during surgery for cryptorchidism or inguinal hernia. Approximately 200 cases have been reported in the literature so far, most
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of whom are adults. We discuss the management in an infant presenting with irreducible inguinal hernia with contralateral undescended testis.
Keywords
Introduction
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46, XY Disorders of Sex Development, Cryptorchidism, Hernia Inguinal, Infant, Male
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Persistent Mullerian Duct Syndrome(PMDS) is a form of 46,XY disorder of sexual differentiation(DSD), in which phenotypic males with 46 XY karyotype have Mullerian duct
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derivatives (i.e uterus, fallopian tubes, cervix and upper two thirds of vagina) [1]. It is a rare congenital disorder, inherited as an autosomal recessive or X-linked recessive trait [2]. It is caused by either a mutation in the gene for Mullerian Inhibiting Substance (also called AntiMullerian Hormone; MIS/ AMH) or a defect in the receptor for MIS/AMH[3]. The condition is called as hernia uteri inguinale when a testis and the Mullerian derivatives are found in an inguinal hernia [4]. Of the nearly 200 cases of PMDS reported over the last 75 years, very few have been diagnosed early in infancy [5].
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ACCEPTED MANUSCRIPT We present a two month old infant with male external genitalia having Mullerian duct remnants with irreducible inguinal hernia, on the side contralateral to the undescended testis.
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We discuss the formulation of an investigative protocol and treatment plan for such cases.
Case report
A two month old infant reared as a male, presented with a history of painful left
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inguino-scrotal swelling. Left irreducible inguinal hernia with right non-palpable undescended testis was found on physical examination. On left inguinal exploration,
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ipsilateral gonad connected to fallopian tube and uterus were identified. On slight traction, the contralateral fallopian tube and gonad were delivered (Figs 1). Wedge biopsies were taken from both the gonads. The processus vaginalis was sutured after repositioning all the above structures into the abdominal cavity. The post-operative course was uneventful.
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Gonadal biopsies showed immature seminiferous tubule and the karyotype was 46,XY. The levels of male and female hormones [testosterone, leutenizing hormone (LH), follicle stimulating hormone (FSH), 17-alpha hydroxy progesterone (AHP)] were within the
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normal limits for age. Baseline testosterone was 67ng/dL and post HCG stimulation testosterone was 647ng/dL, indicating a normally functioning testicular tissue. The AMH was
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< 0.05pmol/L, indicating type I defect. During definitive surgery, uterus, fallopian tubes and a portion of vagina as distal as
possible were excised with mucosal stripping of the remaining (Fig 2a). Owing to close anatomic association, a sliver of uterine walls was left attached to the vas bilaterally in order to preserve their blood supply. Intrascrotal positioning of testes (Fig 2b) and biopsy confirmation of infantile uterus with bilateral tubal structures was done.
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ACCEPTED MANUSCRIPT Discussion The Chicago consensus of DSD categorisation enlists PMDS as a 46,XY disorder of androgen dependent target tissue[1]. The condition was first described by Nilson in 1939, and since then over 200 cases have been reported in the English literature [5]. Large number
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of these case reports are from the older age group [6], because the condition is often missed during initial surgery or investigative work-up owing to its rarity. Awareness and and early detection of PMDS helps in performing definitive surgery at an early age, thereby reducing
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the impact of various medical, social and psychological problems associated with this
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condition.
85% cases of PMDS occur because of a mutation in either AMH synthesis gene on chromosome 19(type I PMDS, 45%), or a defect in AMH receptor gene on chromosome 12(type II PMDS, 40%). In the remaining, the cause for PMDS is unknown (Idiopathic PMDS). Absent AMH activity is physiologic in 46 XX individuals, but in genotypically male
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(46 XY) patients it results in non-regression of Mullerian structures. Morphologically, PMDS is divided into female form (10-20%) with bilateral cryptorchidism and male form (80-90%)
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with unilateral cyrporchidism and contralateral inguinal hernia. Further sub-divisions of male form includes hernia uteri inguinalis with TTE as type I and the classic hernia uteri inguinalis
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as type II [7]. The index case was a male type II form. The diagnosis is often incidental during surgery for cryptorchidism, inguinal hernia or
laparotomy for an unrelated cause, or during investigation for infertility in adulthood. The rarity of occurrence and the often surprise diagnosis, puts the surgeon in a dilemma about its management. As in the index case, typically the patients are males with unilateral undescended testis and inguinal hernia. Bilateral cryptorchidism occurs in only 10% cases. Obstructive uropathy or polyorchidism may be other rarer presentations. MIS has been proposed to stimulate gubernaculum enlargement in the male embryo. In PMDS patients with 3
ACCEPTED MANUSCRIPT either a deficiency of or resistance to MIS, failure of gubernacular masculinization occurs. Hence, it remains long and thin akin to the round ligament in females. This gives the undescended testis undue mobility, allowing the testis to prolapse into the processus vaginalis accounting for the apparent ‘descent’. This phenomenon was also demonstrated in the The mobile testis is thus exposed to an increased risk of torsion and
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described case.
subsequent degeneration.
A clinically manifest inguinal hernia is present in 10-15% of undescended testis,
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although a patent processus vaginalis is present in all [8]. Therefore, a high index of
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suspicion in all cases of combined hernia and cryptorchidism should increase the preoperative diagnostic yield of PMDS. An ultrasound of the inguino-scrotal region and pelvis in all such suspicious cases may prove to be a useful tool for pre-operative diagnostic clarity (Fig 3).
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The standard laboratory investigations for these children include karyotyping and MIS levels. Pre-operative abnormal MIS levels can help to establish an early diagnosis in suscipious cases.
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If PMDS is discovered as an unexpected finding while operating, biopsy of the gonadal tissue and Mullerian structures is warranted. Parental counselling about the complex
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pathophysiology should be done, keeping in mind the psychosocial implications. Once the diagnosis of PMDS is confirmed, the surgical management consists of excision of Mullerian remnants with orchidopexy. With the increasing awareness of malignancy, especially adenocarcinoma, in Mullerian remnants meticulous salpingectomy and hystrectomy is now the recommended treatment. This should be done without compromising the integrity or vascularity of the vas deferens, which run in close proximity to the fallopian tubes and vagina. When technically difficult, a sliver of Mullerian tissue can be left attached to the vas,
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ACCEPTED MANUSCRIPT destroying the mucosa by either stripping or electrocoagulation. Destruction of the mucosa reduces the risk of malignancy and also obliterates the residual cavity by formation of adhesions. This can be achieved either laparoscopically for bilateral non palpable gonads or
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by open surgical technique [5]. Even in the normally descended testicle, spermatogenesis is often impaired in these patients. Infertility is common because most patients have azoospermia [9]. The incidence of germ cell tumours associated with PMDS is reported to be nearly 10%, which is comparable
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to that associated with other causes of intra-abdominal testis [10]. Owing to this risk,
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orchiectomy is required if testis cannot be brought down into the scrotum.
Conclusion
PMDS is a rare disorder detected incidentally while operating for other causes. An
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investigative protocol aids in proper management, thereby avoiding dilemma for the surgeons
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and psycho-social implications on the parents.
None
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Conflict of Interest
Financial support None
References
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ACCEPTED MANUSCRIPT 1. Al-Sherbiny M. Disorders of sexual differentiation: I.Genetic and Pathology. Arab J Urol 2013;11:19-26 2. Sloan WR, Walsh PC. Familial persistent Mόllerian duct syndrome. J Urol 1978;115:459-61
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3. Hutson JM, Davidson PM, Reece LA, Baker ML, Zhou BY. Failure of gubernacular development in the Persistent Mullerian Duct Syndrome allows herniation of the testis. Pediatr Surg Int 1994;9:544-546
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4. Meyer T, Adam P, Hocht B. Persistent Mullerian Duct Syndrome – A case based
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algorithm. Eur J Pediatr Surg 2010;20 (3):194-195
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BJU Int 2012;110(11):1084-9
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7. Rehman A, Hasan Z, Amanat S, Shaukat T, Saeed A, Jamil K et al. Combined Persistent Mullerain Duct Syndrome, Transverse testicular ectopia and Mosaic
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Klinefelter’s syndrome. J Coll Physicians Surg Pak 2009;18(6):375-377
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9. Souto CA, Oliveira Mda C, Teloken C, Paskulin G, Hoffmann K. Persistence of Mullerian duct derivative syndrome in 2 male patients with bilateral cryptorchidism. J Urol 1995;153:1637
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ACCEPTED MANUSCRIPT 10. Brandley DW, Akbal C, Eugsster E, Hadad N, Havlik RJ, Kaefer M. Persistent Mullerian Duct Syndrome with bilateral abdominal testis: Surgical approach and
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review of the literature. J Ped Urol 2005;1:423-427
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ACCEPTED MANUSCRIPT Title: Persistent Mullerian Duct Syndrome presenting as irreducible inguinal hernia – A surprise surgical finding!
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Names of authors: V Sekhon1, M Luthra2, G Jevalikar3
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Affiliation and addresses of authors: 1 Fellow, Department of Pediatric Surgery, Medanta- The Medicity, Gurgaon - 122001 2 Consultant, Department of Pediatric Surgery, Medanta- The Medicity, Gurgaon - 122001 3 Consultant, Department of Pediatric Endocrinology, Medanta- The Medicity, Gurgaon - 122001
Name : Virender Sekhon e-mail address -
[email protected] Telephone number – +91-983-830-1086
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Corresponding author :
Postal address – 1353, Madan Mahal, Jabalpur (MP)- 482001
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Running title: Persistent Mullerian Duct Syndrome
[Type text]
Fig. 1
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Fig. 2a
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Fig. 2b
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Legends for figures Fig 1. Midline rudimentary uterus (Ut) with fallopian tubes (FT). Both gonads (G) at the two ends. UB – Urinary bladder; (Inset) Lateral view. UB – Urinary bladder, Ut – Uterus, V – Vagina, G – Gonad Fig 2a. Partial dissection of vas deference (Vd) from lateral wall of vagina done on the right side Fig 2b. Bilateral gonads fully mobilized for orchidopexy; (Inset) Specimen showing rudimentary uterus (Ut) with partially resected vagina (V) with fallopian tubes (FT)
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Fig 5. Investigative protocol for PMDS management
