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Case Report |
,
* Department of Endocrinological and Medical
Sciences and Center of Excellence for Biomedical Research, the
Department of Pathology, San Martino Hospital,
Genova, Italy; and the Department of Urology,
University of Genova.
| Correspondence to: Dr Diego Ferone, Dipartimento di Scienze Endocrinologiche e Mediche, Università di Genova, Viale Benedetto XV, 6, 16132 Genova, Italy (e-mail: ferone{at}unige.it). |
| Received for publication April 23, 2007; accepted for publication August 15, 2007. |
In this article, we report the history of a 46-year-old man with a scrotal mass, diagnosed as syringoid eccrine carcinoma, presenting with PMDS, which was incidentally discovered by magnetic resonance imaging (MRI) performed for presurgery stadiation of the scrotal tumor. To our knowledge, this is the first case of an exceptional association between an unusual form of male pseudohermaphroditism and a rare cutaneous tumor in an unusual site, probably due to a previous reconstructive surgery for hypospadia.
Patient. A 46-year-old man presented to our unit for endocrinologic evaluation of a sexual ambiguity documented by MRI that showed an upper vagina and a formed uterus. The MRI was performed for a presurgical tumoral stadiation of a cancer diagnosed 7 months before (Figure 1). A subsequent cystoscopy showed a feminine urethra and a small prostate as well.
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Histology showed an eccrine tumor (Figure 2), consisting mainly of numerous tubular structures, small cords, and nests extending from the reticular dermis to the subcutaneous tissue (Figure 2A and B), which often form syringoma-like ducts. Periodic acid-Schiff–positive diastase-resistant material was observed in the lumina of the tubular structures (Figure 2C). Immunohistochemical analysis revealed diffuse positivity for carcinoembryonic antigen (Figure 2D), cytokeratin (CK) 7 (Figure 2E), and CK 8, 18, and 19 (Figure 2F), suggesting a sweat gland secretory differentiation.
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In our endocrine unit, the full endocrinologic evaluation showed a hypergonadotropic hypogonadism. The levels of the remaining hormone were within the normal range (Table 1). Karyotype was male (46,XY), and the patient had a normal testicular response to human chorionic gonadotropin (hCG; basal testosterone of 8.7 nmol/L rose to 24.9 nmol/L after intramuscular administration of 5000 IU of hCG) (Figure 3).
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Because of the histologic features and the limited consistency of the remaining perineal tissue, neither chemotherapy nor radiotherapy was advised by the oncologist. After 3 months the patient underwent another operation because the tumor had spread in the perineal region and lower abdomen and anal stenoses developed, which required colostomy. The patient is currently still alive and has experienced several subocclusive abdominal episodes, which significantly worsened his quality of life.
Discussion
Antimüllerian hormone (AMH), also called MIS, is a 140-kDa
glycoprotein produced by Sertoli cells at the initiation of testicular
differentiation and is responsible for the regression of the müllerian
ducts, the first sign of phenotypic sex differentiation in the male fetus.
Mutations of the AMH or AMH type II receptor (AMHR2) gene
lead to a rare form of autosomal recessive male pseudohermaphroditism, named
PMDS and characterized by the persistence of müllerian derivates, uterus,
fallopian tubes, and upper part of the vagina in normally virilized 46,XY
males. Affected individuals are otherwise normally virilized, undergo normal
male puberty, and may be fertile if the testes, tightly attached to the
fallopian tubes, can be returned into the scrotum.
PMDS is also described in other species, such as mixed-breed dogs, cats, and goats (Meyers-Wallen et al, 1993; Kuiper et al, 2004; Josso et al, 2005). In humans, diagnosis is based on clinical features (eg, persistence of müllerian ducts) that may be documented occasionally by radiologic exams and in prepubertal boys, by measurement of AMH levels. Indeed, prenatal AMH expression levels are high in boys and negligible in girls. In boys, the serum concentration of the hormone is low at birth, rapidly rises to peak values during late infancy, and then slowly decreases to the adult range at puberty. Therefore, hormones, such as inhibin and AMH, specifically reflect Sertoli cell function, offering a noninvasive measurement of seminiferous tubular integrity. Moreover, AMH inhibits the differentiation and proliferation of Leydig cell precursors and down-regulates androgen steroidogenesis in mature Leydig cell tumor lines (Misra et al, 2002). PMDS can also be associated with complete androgen insensitivity (Swanson and Coronel, 1993).
More recently Klattig et al (2007) focused attention on the fact that Wilms tumor protein WT1 is an activator of the AMHR2 gene, underlining a molecular mechanism behind the association of PMDS and this type of pediatric cancer.
Clinical features of PMDS frequently observed are cryptorchidism, inguinal hernia, and very rarely, transverse testicular ectopia, the condition of both testes descending through the same inguinal canal into the same scrotal sac (Berkmen, 1997; Kella et al, 2005; Tiryaki et al 2005; Liang et al, 2006; Boleken et al, 2007). Anorchia may be present as well, suggesting a further defect of embryogenesis, in addition to the failure of müllerian duct regression.
Different neoplasms have been ascribed to PMDS. Carcinoma cells may develop from testes or müllerian ducts. Monolateral or bilateral seminoma is the most frequent tumor reported to be associated with PMDS (Snow et al, 1985; van Laarhoven et al, 1991; Williams et al, 1994; Dueñas et al, 2001; Bucci et al, 2002; Yuksel et al, 2006). Conversely, only 1 case of nonseminomatous testicular tumor has been described (Eastham et al, 1992). Similarly, 1 case of mixed germ cell tumor of the testis (teratoma and embryonal carcinoma), diagnosed 18 years after bilateral orchidopexy (Manassero et al, 2004), and a case of choriocarcinoma with teratoma arising from intra-abdominal testis have been reported (Narlawar et al, 2001; Giri et al, 2004). A case of tumor in a supernumerary abdominal testis (polyorchidism) in a man has been described as well (Kulkarni et al, 1992). A clear adenocarcinoma of the müllerian duct, discovered incidentally at autopsy, has been diagnosed, and it represents the first case of malignant transformation of the persistent müllerian duct structures in PMDS (Shinmura et al, 2002).
Here we report the first case of PMDS associated with a very rare skin tumor, a syringoid eccrine carcinoma, occurring in an unusual site. However, this patient had a history of several operations for hypospadia during the prepubertal age, when skin borders from other body regions were added for reconstructive surgery.
Malignant appendage tumors with eccrine differentiation are a rare group of neoplasms with biologic capacity for local tissue infiltration and metastases. The etiology of these tumors is very complex (Goldestein et al, 1982; Murphy and Elder, 1991). It is possible to separate them into 2 groups: 1) malignant variants that include benign eccrine neoplasms and 2) primary eccrine carcinomas without benign counterparts. Syringoid eccrine carcinoma (Moy et al, 1991; Evans et al, 1995), otherwise called malignant chondroid eccrine syringoma, syringomatous carcinoma, and in some cases, microcystic adnexal carcinoma (McKee et al, 1990) or sclerosing sweat duct carcinoma (Cooper et al, 1985), can be included in the first group. It is usually found on the upper lip, nasolabial area, periorbital region, and less frequently on the axilla, scalp, and trunk (Mehregan et al, 1983; Ohnishi et al, 2002). It occurs on the dermis but often extends into the subcutis or deeper. Metastases rarely occur, but local recurrences of these tumors may be massive; therefore, their complete primary surgical excision is very important.
In this case, the tumor was found in the perineal scrotal skin, an unusual site. It was aggressive with an infiltrative growth pattern and multiple local recurrences with abdominal invasion. Indeed, 6 months after the major demolitive and reconstructive surgery, a colostomy was performed because constipation developed due to the neoplastic invasion of the rectal and anal tracts.
To our knowledge, this is the first case in the literature of an exceptional association between PMDS and a syringoid eccrine carcinoma of the perineal-scrotal skin. However, in our opinion, this is not likely due to a molecular link. The most probable reason was the previous reconstructive urologic surgery (implants from different cutaneous area) performed for hypospadia several years earlier.
Footnotes
This study was partially supported by grants from the Ministero dell'Università e della Ricerca (2002067251-001) and the University of Genova.
These authors have contributed equally to this work. 
References
Belville C, Van Vlijmen H, Ehrenfels C, Pepinsky B, Rezaie AR,
Picard JY. Mutations of the anti-müllerian hormone gene in patients with
persistent müllerian duct syndrome: biosynthesis, secretion, and
processing of the abnormal proteins and analysis using a three-dimensional
model. Mol Endocrinol. 2004; 18: 708
–721.
Berkmen F. Persistent müllerian duct syndrome with or without transverse testicular ectopia and testis tumours. Br J Urol. 1997;79: 122 –126.[Medline]
Boleken ME, Kaya M, Güran S, Memeto
lu ME, Kanmaz T,
Yücesan S. Persistent mullerian duct syndrome with transverse testicular
ectopia. Int Urol Nephrol. 2007 [Epub
ahead of print].
Bucci S, Liguori G, Buttazzi L, Bussani R, Trombetta C. Bilateral testicular carcinoma in patient with the persistent müllerian duct syndrome. J Urol. 2002; 167: 1790 .[CrossRef][Medline]
Cooper PH, Mills SE, Leonard DD, Santa Cruz DJ, Headington JT, Barr RJ, Katz DA. Sclerosing sweat duct (syringomatous) carcinoma. Am J Surg Pathol. 1985;9: 422 –433.[Medline]
Dueñas A, Saldívar C, Castillero C, Flores G, Martínez P, Jiménez M. A case of bilateral seminoma in the setting of persistent mullerian duct syndrome. Rev Invest Clin. 2001;53: 193 –196.[Medline]
Eastham JA, McEvoy K, Sullivan R, Chandrasoma P. A case of simultaneous bilateral nonseminomatous testicular tumors in persistent müllerian duct syndrome. J Urol. 1992; 148: 407 –408.[Medline]
Evans AT, Parham DH, Van Niekerk LJA. Metastasising eccrine syringomatous carcinoma. Histopathology. 1995; 26: 185 –187.[CrossRef][Medline]
Giri SK, Berney D, O'Driscoll J, Drumm J, Flood HD, Gupta RK. Choriocarcinoma with teratoma arising from an intra-abdominal testis in patient with persistent müllerian duct syndrome. Lancet Oncol. 2004;5: 451 –452.[CrossRef][Medline]
Goldestein DJ, Barr RJ, Santa Cruz DJ. Microcystic adnexal carcinoma; a distinct clinicopathologic entity. Cancer. 1982;50: 566 –572.[CrossRef][Medline]
Josso N, Belville C, di Clemente N, Picard JY. AMH and AMH receptor
defects in persistent müllerian duct syndrome. Hum Reprod
Update. 2005;11: 351
–356.
Kella N, Rathi PK, Memon S, Ahuja P, Memon SA. Persistent mullerian duct syndrome with transverse testicular ectopia. J Coll Physician Surg Pak. 2005;15: 119 –120.
Klattig J, Sierig R, Kruspe D, Besenbeck B, Englert C. Wilm's tumor
protein Wt1 is an activator of the anti-müllerian hormone receptor gene
AMHR2. Mol Cell Biol. 2007; 27: 4355
–4364.
Kuiper H, Wagner F, Drögemüller C, Distl O. Persistent
müllerian duct syndrome causing male pseudohermaphroditism in a
mixed-breed dog. Vet Rec. 2004; 155: 400
–401.
Kulkarni JN, Bhansali MS, Tongaonkar HB, Kamat MR, Borges AM. Carcinoma in the third testis in a case of polyorchidism and persistent müllerian structure syndrome. Eur Urol. 1992; 22: 174 –176.[Medline]
Liang YY, Zheng FF, Dai YP, Zheng KL, Zhou JX. Persistent muellerian duct syndrome with transverse testicular ectopia. Asian J Androl. 2006;8: 745 –747.[CrossRef][Medline]
MacLaughlin DT, Donahoe PK. Sex determination and differentiation. N Engl J Med. 2004; 350: 367 –378.[CrossRef][Medline]
Manassero F, Cuttaneo MG, Morelli G, Salinitri G, Spurio M, Selli C. Mixed germ cell tumor after bilateral orchidopexy in persistent müllerian duct syndrome with transverse testicular ectopia. Urol Int. 2004;73: 81 –83.[CrossRef][Medline]
McKee PH, Fletcher CDM, Rasbridge SA. The enigmatic eccrine epithelioma (eccrine syringomatous carcinoma). Am J Dermatopathol. 1990;13: 552 –561.
Mehregan AH, Hashimoto K, Rahbari H. Eccrine adenocarcinoma. A
clinicopathologic study of 35 cases. Arch Dermatol. 1983; 119: 104
–114.
Meyers-Wallen VN. Genetics of sexual differentiation and anomalies in dogs and cats. J Reprod Fertil. 1993; 47: 441 –452.
Misra M, MacLaughlin DT, Donahoe PK, Lee MM. Measurement of
mullerian inhibiting substance facilitates management of boys with
microphallus and cryptorchidism. J Clin Endocrinol
Metab. 2002;87: 3598
–3602.
Moy RL, Rivkin JE, Lee H, Brooks WS, Zitelli JA. Syringoid eccrine syringomatous carcinoma. J Am Acad Dermatol. 1991; 24: 857 –860.[Medline]
Murphy GF, Elder DE, eds. Non-Melanocytic Tumors of the Skin. Washington, DC: Armed Forces Institute of Pathology; 1991 .
Narlawar RS, Shah JR, Parikh V, Patankar T. Persistent mullerian duct syndrome with teratoma in an ectopic testis: imaging features. Eur Radiol. 2001; 11: 955 –958.[CrossRef][Medline]
Ohnishi T, Kaneko S, Egi M, Takizawa H, Watanabe S. Syringoid eccrine carcinoma. Report of a case with immunohistochemical analysis of cytokeratin expression. Am J Dermatopathol. 2002; 24: 409 –413.[CrossRef][Medline]
Shinmura Y, Yokoi T, Tsutsui Y. A case of clear cell adenocarcinoma of the müllerian duct in persistent müllerian duct syndrome: the first reported case. Am J Surg Pathol. 2002; 26: 1231 –1234.[CrossRef][Medline]
Snow BW, Rowland RG, Seal GM, Williams SD. Testicular tumor in patient with persistent müllerian duct syndrome. Urology. 1985;26: 495 –497.[CrossRef][Medline]
Swanson ML, Coronel EH. Complete androgen insensitivity with persistent müllerian structures. A case report. J Reprod Med. 1993;38: 565 –568.[Medline]
Tiryaki T, Hucumenolu S, Atayurt H. Transverse testicular
ectopia associated with persistent müllerian duct syndrome. A case
report. Urol Int. 2005; 74: 190
–192.[CrossRef][Medline]
van Laarhoven CJ, Juttmann JR, Pijpers PM, Roukema JA. A testicular tumour in the left adnex. The persistent mullerian duct syndrome with testicular malignancy. Eur J Surg Oncol. 1991; 17: 97 –98.[Medline]
Williams JC, Merguerian PA, Schned AR, Amdur RJ. Bilateral testicular carcinoma in situ in persistent müllerian duct syndrome: a case report and literature review. Urology. 1994; 44: 595 –598.[CrossRef][Medline]
Yuksel B, Saygun O, Hengirmen S. Persistent müllerian duct syndrome associated with irreducible inguinal hernia, bilateral cryptorchidism and testicular neoplasia: a case report. Acta Chir Belg. 2006;106: 119 –120.[Medline]
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