DOI: 10.1148/rg.232025141
(Radiographics. 2003;23:309-313.)
© RSNA, 2003
Best Cases from the AFIP
Persistent Müllerian Duct Syndrome1
Helena M. Dekker, MD,
Igle J. de Jong, MD, PhD,
Joyce Sanders, MD and
Rienhart F. E. Wolf, PhD
1 From the Departments of Radiology (H.M.D., R.F.E.W.), Urology (I.J.d.J.), and Pathology (J.S.), University Hospital Groningen, The Netherlands. Received August 20, 2002; revision requested September 17 and received October 15; accepted October 16. Address correspondence to R.F.E.W., Hanzeplein 1, 9713 GZ Groningen, The Netherlands (e-mail: r.f.e.wolf@rad.azg.nl).
Index Terms: Fetus, growth and development • Genitourinary system, abnormalities, 84.1473, 84.1477 • Genitourinary system, MR, 84.1214 • Hernia, inguinal, 796.1571 • Sex, 84.1473 • Testis, undescended, 847.1477
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History
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A 73-year-old man presented with complaints of progressive pain in the left lower quadrant associated with constipation. These complaints were reduced by having the patient lie on his right side. There was no history of micturation problems.
At physical examination, a palpable mass was detected in the left lower abdomen, together with an ipsilateral reducible inguinal hernia. No testis was found in the right side of the scrotum. Cystoscopy showed no abnormalities. Laboratory studies revealed minimal renal function abnormalities without hematuria and a low level of testosterone (3.1 nmol/L [0.89 ng/mL]). A chromosome analysis revealed a normal male karyotype of 46 XY.
Past medical history included repair of a left inguinal hernia and left orchiopexy (performed in 1945), appendectomy, right nephrectomy for pyonephrosis with nephrolithiasis, and primary infertility.
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Imaging Findings
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Ultrasonography (US) of the genitalia showed multiple cysts located in the scrotum and extending into the left inguinal canal. A solid mass with a central cystic component was identified in the lower abdomen. These US findings were thought to represent a tumor; however, a definite diagnosis could not be established.
Magnetic resonance (MR) imaging of the abdomen showed a lower abdominal mass at the ventral side of the urinary bladder. The wall of the mass was thickened and had low signal intensity at T1-weighted imaging and mixed intermediate and high signal intensity at T2-weighted imaging (Fig 1). Smooth, well-defined lesions with low signal intensity were seen within the wall with both sequences. A portion of the mass was seen to herniate into the left inguinal canal (Fig 2). The mass was filled with fluid that had high signal intensity at both T1- and T2-weighted MR imaging, a finding that was compatible with blood products. The mass was contiguous with a thin-walled structure posterior to it that also contained high-signal-intensity fluid. The signal intensity characteristics and morphologic appearance of the mass suggested a distended blood-filled uterus and vagina (hematometrocolpos), with the low-signal-intensity lesions in the wall representing leiomyomas (Figs 1–3). A structure with low signal intensity at T1-weighted MR imaging and high signal intensity at T2-weighted imaging was identified on the left side of the scrotum (Fig 4), and a structure with low signal intensity at T1-weighted imaging and mixed intermediate and high signal intensity at T2-weighted imaging was detected in the right side of the abdomen (Fig 5). These two structures represented the testes.
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Figure 1a. Axial turbo spin-echo T1-weighted (repetition time msec/echo time msec = 874/12) (a) and T2-weighted (4,902/132) (b) MR images demonstrate a mass (the uterus) (open arrow) with an inhomogeneous wall and a central high-signal-intensity cystic component. The high-signal-intensity oval structure at the caudal end of the uterus represents the vagina (solid arrow).
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Figure 1b. Axial turbo spin-echo T1-weighted (repetition time msec/echo time msec = 874/12) (a) and T2-weighted (4,902/132) (b) MR images demonstrate a mass (the uterus) (open arrow) with an inhomogeneous wall and a central high-signal-intensity cystic component. The high-signal-intensity oval structure at the caudal end of the uterus represents the vagina (solid arrow).
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Figure 2a. On coronal T1-weighted (a) and axial T2-weighted (b) MR images, the uterus (solid arrow in a, arrowhead in b) is partly herniated into the left inguinal canal. The low-signal-intensity nodules in the uterine wall (open arrows in a) represent leiomyomas.
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Figure 2b. On coronal T1-weighted (a) and axial T2-weighted (b) MR images, the uterus (solid arrow in a, arrowhead in b) is partly herniated into the left inguinal canal. The low-signal-intensity nodules in the uterine wall (open arrows in a) represent leiomyomas.
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Pathologic Evaluation
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Exploratory laparotomy revealed an enlarged uterus. The left side of the uterus was partly situated in the left inguinal canal. The left adnexa was found in the scrotum. At surgery, brown fluid was found in the vagina. The uterus, vagina, and adnexa were removed en bloc.
Gross pathologic examination showed an enlarged uterus (18 x 14 x 7 cm) with intramural and submucosal leiomyomas, the largest of which was 5 cm in diameter. The vagina was situated at the caudal end of the uterus and measured 7 x 2 cm. The right adnexa resembled an ovary with a 7-cm fallopian tube. The left adnexa appeared to be a testicle (4.5 x 3 x 2.5 cm) surrounded by fat, connective tissue, and blood vessels. The left fallopian tube could not be identified. Cystic structures filled with clear and brown fluid were identified alongside the testicle. No cervix was found (Figs 6, 7).
Histologic examination showed the uterus to be composed of a muscle layer lined with a single layer of tubal epithelium without atypia, with foci of underlying endometrial stroma. Multiple leiomyomas without signs of malignancy were observed in the muscle wall (Fig 8). Although the gonad in the right adnexa was thought to be an ovary, at histologic analysis it proved to be a testis with complete atrophy and containing fibrosis and calcifications. The left testicle demonstrated atrophy and Leydig cell hyperplasia, with no active spermatogenesis (Fig 9). A rete testis with a normal relationship to the testicle was present on both sides. No ovarian tissue was found. Structures lined with tubal epithelium were detected on both sides of the uterus and most likely represented fallopian tube remnants. Adjacent to the left adnexa, simple cystic structures lined with a single layer of tubal epithelium without atypia were present.
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Figure 8. Photomicrograph (original magnification, x25; hematoxylin-eosin stain) shows a leiomyoma (arrow) composed of interlacing bundles of smooth muscle cells without cytonuclear atypia. * = adjacent muscle wall of the uterus.
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Figure 9. Photomicrograph (original magnification, x100; hematoxylin-eosin stain) shows complete atrophy of the left testis, with fibrosis, total absence of germ cells, and Leydig cell hyperplasia (nodular cellular structures, with eosinophilic cytoplasm and round uniform nuclei) (arrows).
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Discussion
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Persistent müllerian duct syndrome (PMDS) is a form of internal male pseudohermaphroditism caused by a deficiency of müllerian-inhibiting factor (MIF) (1). Müllerian derivatives (ie, fallopian tubes, uterus, upper part of the vagina) are present in otherwise normally virilized XY patients. PMDS patients are both karyotypically and phenotypically male, with normal development of secondary sex characteristics.
In a human fetus, both müllerian and wolffian ducts are present at 7 weeks gestation. Müllerian ducts and wolffian ducts are the anlagen of the female and male reproductive tracts, respectively. In the XY fetus, the testis differentiates by the end of the 7th gestational week. Sertoli cells begin to secrete MIF, which is responsible for the regression of the müllerian ducts. Normal sex differentiation in males is controlled by testosterone and MIF, both of which are produced by the fetal testes. Testosterone has a direct local effect on the wolffian ducts, including differentiation into the epididymides, vas deferens, and seminal vesicles. Formation of the urogenital sinus and male external genitalia requires in situ conversion of testosterone into dihydrotestosterone.
PMDS patients develop both wolffian and müllerian structures due to a deficiency of MIF. The gene responsible for MIF is localized on the short arm of chromosome 19. Mapping of this gene on an autosome implies an autosomal mode of inheritance for PMDS. PMDS is a rare condition, with only about 100 cases described in the literature. The syndrome was first described by Nilson in 1939 (2). Its prevalence has probably been underestimated because (a) in the past, surgical correction of undescended testis was not always undertaken, and (b) the presence of müllerian derivatives may not have been identified correctly.
Two anatomic variants of PMDS have been described (3–5). The most common variant (male form) is encountered in 80%–90% of cases and is characterized by unilateral cryptorchidism with a contralateral inguinal hernia. The male form of PMDS can be further categorized into two clinical conditions, depending on the contents of the hernial sac. The first condition, hernia uteri inguinalis, is typically characterized by a descended testis and herniation of the ipsilateral corner of the uterus and the ipsilateral fallopian tube into the inguinal canal. The second condition, known as crossed testicular ectopia, is characterized by herniation of both testes and fallopian tubes and the entire uterus. The second anatomic variant of PMDS (female form) is encountered in only 10%–20% of cases and is characterized by bilateral cryptorchidism, with the uterus fixed in the pelvis and both testes embedded in the round ligaments. It has been suggested that the mobility of the müllerian structures is an important factor in the development of the different clinical conditions in PMDS. If the uterus and fallopian tubes are freely mobile, they may be pulled into the inguinal canal during testicular descent. Alternatively, if the müllerian structures are relatively immobile, testicular descent may be impeded, resulting in testicular ectopia (4).
Infertility is common, with absence of spermatozoa seen at semen analysis. However, there have been a few reported cases of fertility, although absolute proof of paternity was not established (2).
As in other patients with undescended testis, there is an increased risk of malignant transformation, and a variety of testicular malignancies have been reported in association with PMDS. In a study by Beyribey et al (6), the overall prevalence of gonadal malignant transformation in affected patients was 15%, a rate that is similar to that of malignancy in abdominal testis in cryptorchid men.
Distinguishing PMDS from other intersex disorders is critical. A karyotype and assessment of testicular response to chorionic gonadotropin stimulation are essential to verify both genetic sex and the existence of functional testicular tissue. Testicular biopsy must be performed to complete the evaluation.
Most of the structural abnormalities can be suggested by pelvic US findings. However, in most cases encountered in general practice, the diagnosis is not known, and the radiologist may not recognize the different structures. Abdominal MR imaging will help distinguish the different structures in such patients on the basis of signal intensity characteristics and morphologic features. The multiplanar imaging capability of MR imaging delineates the relationships of these structures to the adjacent pelvic organs (7).
Recognition of PMDS is important for prognosis. The main therapeutic considerations are the potential for fertility and malignant changes. The management of PMDS is controversial. Most clinicians recommend that the persistent müllerian derivatives be removed (8,9). On the other hand, the vas deferens lies close to the uterus and may be incorporated into the vaginal wall, so that complete excision of these structures will divide the vas deferens. Surgical techniques for preserving the vas deferens have been described. Mobilization of the gonadal blood vessels may be necessary for completion of the orchiopexies. Repair of the inguinal hernia must be performed if applicable. Orchiectomy should be performed for any testis that cannot be mobilized into a palpable position.
Because PMDS may be discovered incidentally during pediatric surgery for undescended testis or inguinal hernia, the initial procedure may need to include replacement of the gonads and müllerian structures within the pelvis and repair of the inguinal hernia. After confirmation of the diagnosis of PMDS, definitive surgery should be performed to remove the corpus of the uterus and fallopian tubes to enable fixation of the testes in the scrotum. The patient or his family should be completely informed of the diagnosis, the surgical options, and the need for long-term follow-up. Finally, genetic counseling must be offered to the patient or his parents because of the possible chromosomal origin of the syndrome (2).
The patient in this case made a good recovery. The testosterone level was already low prior to surgery, and one would expect this level to decline further after surgical removal of both testes. Nevertheless, the patient refused testosterone replacement therapy. As mentioned earlier, he had previously undergone surgical repair of a left inguinal hernia and orchiopexy. However, the presence of müllerian derivatives had been overlooked.
This case is unique in terms of the patient’s advanced age at presentation and the development of leiomyomas in the uterus. Abdominal MR imaging proved to be an excellent tool for visualization of the complex pelvic anatomy.
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Footnotes
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Abbreviations: MIF = müllerian inhibiting factor,
PMDS = persistent müllerian duct syndrome
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References
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- Rey R, Picard JY. Embryology and endocrinology of genital development. Baillieres Clin Endocrinol Metab 1998; 12:17-33.[CrossRef][Medline]
- Sheehan SJ, Tobbia IN, Ismail MA, Kelly DG, Duff FA. Persistent müllerian duct syndrome: review and report of 3 cases. Br J Urol 1985; 57:548-551.[Medline]
- Josso N, Picard JY, Imbeaud S, di Clemente N, Rey R. Clinical aspects and molecular genetics of the persistent müllerian duct syndrome. Clin Endocrinol 1997; 47:137-144.[CrossRef][Medline]
- Vandersteen DR, Chaumeton AK, Ireland K, Tank ES. Surgical management of persistent müllerian duct syndrome. Urology 1997; 49:941-945.[CrossRef][Medline]
- Belville C, Josso N, Picard JY. Persistence of müllerian derivatives in males. Am J Med Genet 1999; 89:218-223.[CrossRef][Medline]
- Beyribey S, Cetinkaya M, Adsan O, Memis A, Ozturk B. Persistent müllerian duct syndrome: reports of two cases. Scand J Urol Nephrol 1993; 27:563-565.[Medline]
- Di Cesare E, Di Bartolo De Vincentiis V, Maffey MV, Splendiani A, Masciocchi C. US and MRI in a case of persistent müllerian duct syndrome. Pediatr Radiol 1998; 28:865-867.[CrossRef][Medline]
- Loeff DS, Imbeaud S, Reyes HM, Meller JL, Rosenthal IM. Surgical and genetic aspects of persistent müllerian duct syndrome. J Pediatr Surg 1994; 29:61-65.[CrossRef][Medline]
- Fernandes ET, Hollabaugh RS, Young JA, Wilroy SR, Schriock EA. Persistent müllerian duct syndrome. Urology 1990; 36:516-518.[CrossRef][Medline]
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History
Imaging Findings
